Brazilian Journal of Cardiovascular Surgery 28.4

28.4 OCTOBER/DECEMBER 2013

BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY / REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR

VOL. 28 Nยบ 4 OCTOBER/DECEMBER 2013

20

14

HEART TEAM

O paciente em primeiro lugar

CONGRESSO DA SOCIEDADE BRASILEIRA

4º Simpósio de Enfermagem em Cirurgia Cardiovascular 4º Simpósio de Fisioterapia em Cirurgia Cardiovascular 4º Simpósio de Perfusão em Cirurgia Cardiovascular 3º Congresso Acadêmico em Cirurgia Cardiovascular

SBCC V

DE CIRURGIA CARDIOVASCULAR

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EDITOR/EDITOR Prof. Dr. Domingo M. Braile - PhD São José do Rio Preto - SP - Brasil domingo@braile.com.br

BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY

EDITORES ANTERIORES/FORMER EDITORS • Prof. Dr. Adib D. Jatene PhD - São Paulo (BRA) [1986-1996] • Prof. Dr. Fábio B. Jatene PhD - São Paulo (BRA) [1996-2002]

EDITOR EXECUTIVO EXECUTIVE EDITOR Ricardo Brandau Pós-graduado em Jornalismo Científico - S. José do Rio Preto (BRA) brandau@sbccv.org.br

ASSESSORA EDITORIAL/EDITORIAL ASSISTANT Rosangela Monteiro Camila Safadi PhD - São Paulo (BRA) S. José do Rio Preto (BRA) rosangela.monteiro@incor.usp.br camila@sbccv.org.br

EDITORES ASSOCIADOS/ASSOCIATE EDITORS • Antônio Sérgio Martins • Gilberto Venossi Barbosa • José Dario Frota Filho • José Teles de Mendonça • Luciano Cabral Albuquerque • Luis Alberto Oliveira Dallan • Luiz Felipe Pinho Moreira

Botucatu (BRA) Porto Alegre (BRA) Porto Alegre (BRA) Aracaju (BRA) Porto Alegre (BRA) São Paulo (BRA) São Paulo (BRA)

• Manuel Antunes • Mario Osvaldo P. Vrandecic • Michel Pompeu B. Oliveira Sá • Paulo Roberto Slud Brofman • Ricardo C. Lima • Ulisses A. Croti • Walter José Gomes

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EDITOR DE ESTATÍSTICA/STATISTICS EDITOR • Orlando Petrucci Jr.

Campinas (BRA)

CONSELHO EDITORIAL/EDITORIAL BOARD • Adib D. Jatene • Adolfo Leirner • Adolfo Saadia • Alan Menkis • Alexandre V. Brick • Antônio Carlos G. Penna Jr. • Bayard Gontijo Filho • Borut Gersak • Carlos Roberto Moraes • Christian Schreiber • Cláudio Azevedo Salles • Djair Brindeiro Filho • Eduardo Keller Saadi • Eduardo Sérgio Bastos • Enio Buffolo • Fábio B. Jatene • Fernando Antônio Lucchese • Gianni D. Angelini • Gilles D. Dreyfus • Ivo A. Nesralla • Jarbas J. Dinkhuysen • José Antônio F. Ramires • José Ernesto Succi • José Pedro da Silva • Joseph A. Dearani

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VERSÃO PARA O INGLÊS/ENGLISH VERSION • Carolina Zuppardi • Fernando Pires Buosi • Marcelo Almeida

• Joseph S. Coselli • Luiz Carlos Bento de Souza • Luiz Fernando Kubrusly • Mauro Paes Leme de Sá • Miguel Barbero Marcial • Milton Ary Meier • Nilzo A. Mendes Ribeiro • Noedir A. G. Stolf • Olivio Souza Neto • Otoni Moreira Gomes • Pablo M. A. Pomerantzeff • Paulo Manuel Pêgo Fernandes • Paulo P. Paulista • Paulo Roberto B. Évora • Pirooz Eghtesady • Protásio Lemos da Luz • Reinaldo Wilson Vieira • Renato Abdala Karam Kalil • Renato Samy Assad • Roberto Costa • Rodolfo Neirotti • Rui M. S. Almeida • Sérgio Almeida de Oliveira • Tomas A. Salerno

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ÓRGÃO OFICIAL DA SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR DESDE 1986 OFFICIAL ORGAN OF THE BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY SINCE 1986

ENDEREÇO/ADDRESS

Sociedade Brasileira de Cirurgia Cardiovascular

Rua Beira Rio, 45 • 7º andar - Cj. 72 • Vila Olímpia • Fone: 11 3849-0341. Fax: 11 5096-0079. Cep: 04548-050 • São Paulo, SP, Brasil E-mail RBCCV: revista@sbccv.org.br • E-mail SBCCV: sbccv@sbccv.org.br • Site SBCCV: www.sbccv.org.br • Sites RBCCV: www.scielo.br/rbccv / www.rbccv.org.br (também para submissão de artigos)

Publicação trimestral/Quarterly publication Edição Impressa - Tiragem: 250 exemplares

(*)

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR (Sociedade Brasileira de Cirurgia Cardiovascular) São Paulo, SP - Brasil. v. 119861986, 1: 1,2 1987, 2: 1,2,3 1988, 3: 1,2,3 1989, 4: 1,2,3 1990, 5: 1,2,3 1991, 6: 1,2,3 1992, 7: 1,2,3,4 1993, 8: 1,2,3,4 1994, 9: 1,2,3,4 1995, 10: 1,2,3,4

1996, 11: 1,2,3,4 1997, 12: 1,2,3,4 1998, 13: 1,2,3,4 1999, 14: 1,2,3,4 2000, 15: 1,2,3,4 2001, 16: 1,2,3,4 2002, 17: 1,2,3,4 2003, 18: 1,2,3,4 2004, 19: 1,2,3,4 2005, 20: 1,2,3,4

2006, 21: 1 [supl] 2006, 21: 1,2,3,4 2007, 22: 1 [supl] 2007, 22: 1,2,3,4 2008, 23: 1 [supl] 2008, 23: 1,2,3,4 2009, 24: 1 [supl] 2009, 24: 1,2,3,4 2009, 24: 2 [supl] 2010, 25: 1,2,3,4

2010, 25: 1 [supl] 2011, 26: 1,2,3,4 2011, 26: 1 [supl] 2012, 27: 1,2,3,4 2012, 27: 1 [supl] 2013, 28: 1,2,3,4 2013, 28: 1 [supl]

ISSN 1678-9741 - Publicação on-line ISSN 0102-7638 - Publicação impressa RBCCV 44205

CDD 617.4105 NLM18 WG 168

(*) ASSOCIAÇÃO PAULISTA DE BIBLIOTECÁRIOS. Grupo de Bibliotecários Biomédicos. Normas para catalogação de publicações seriadas nas bibliotecas especializadas. São Paulo, Ed. Polígono, 1972

INDEXADA EM • Thomson Scientific (ISI) http://science.thomsonreuters.com • PubMed/Medline www.ncbi.nlm.nih.gov/sites/entrez • SciELO - Scientific Library Online www.scielo.br • Scopus www.info.scopus.com • LILACS - Literatura Latino-Americana e do Caribe em Ciências da Saúde. www.bireme.org • LATINDEX -Sistema Regional de Información en Línea para Revistas Cientificas de America Latina, el Caribe, España y Portugal www.latindex.uam.mx

• ADSAUDE - Sistema Especializado de Informação em Administração de Saúde www.bibcir.fsp.usp.br/html/p/pesquisa_em_ bases_de_dados/programa_rede_adsaude • Index Copernicus www.indexcopernicus.com • Google scholar http://scholar.google.com.br/scholar • EBSCO www2.ebsco.com/pt-br

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR

BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY DEPARTAMENTO DE CIRURGIA DA SOCIEDADE BRASILEIRA DE CARDIOLOGIA DEPARTMENT OF SURGERY OF THE BRAZILIAN SOCIETY OF CARDIOLOGY

“Valorizando o profissional em prol do paciente” DIRETORIA 2011 - 2013 Presidente: Vice-Presidente: Secretário Geral: Tesoureiro: Diretor Científico:

Walter José Gomes (SP) João Alberto Roso (RS) Marcelo Matos Cascudo (RN) Eduardo Augusto Victor Rocha (MG) Fábio Biscegli Jatene (SP)

Conselho Deliberativo:

Bruno Botelho Pinheiro (GO) Henrique Barsanulfo Furtado (TO) José Glauco Lobo Filho (CE) Rui M.S. Almeida (PR) Henrique Murad (RJ)

Editor da Revista: Editor do Site: Editores do Jornal:

Domingo Marcolino Braile (SP) Vinicius José da Silva Nina (MA) Walter José Gomes (SP) Fabricio Gaburro Teixeira (ES) Josalmir José Melo do Amaral (RN) Luciana da Fonseca (SP)

Presidentes das Regionais Afiliadas Norte-Nordeste: Rio de Janeiro: São Paulo: Minas Gerais: Centro-Oeste: Rio Grande do Sul: Paraná: Santa Catarina:

Maurílio Onofre Deininger (PB) Marcelo Sávio da Silva Martins Carlos Manuel de Almeida Brandão Antonio Augusto Miana Luiz Carlos Schimin (DF) Marcela da Cunha Sales Rodrigo Mussi Milani Lourival Bonatelli Filho

Departamentos DCCVPED: DECAM: DECA: DECEN: DEPEX: DECARDIO:

Marcelo B. Jatene (SP) Alfredo Inácio Fiorelli (SP) Luiz Paulo Rangel Gomes da Silva (PA) Rui M. S. Almeida (PR) Melchior Luiz Lima (ES) Miguel Angel Maluf (SP)

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY E-mail: revista@sbccv.org.br Sites: www.scielo.br/rbccv www.rbccv.org.br

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR

ISSN 1678-9741 - Online issue ISSN 0102-7638 - Printed issue RBCCV 44205

Impact Factor: 0.809

BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY Rev Bras Cir Cardiovasc, (São José do Rio Preto, SP - Brazil) oct/dec - 2013;28(4) 435-580

CONTENTS/SUMÁRIO EDITORIAIS/EDITORIALS

Animal research and cardiovascular surgery Pesquisa com animais e a cirurgia cardiovascular Domingo M. Braile.................................................................................................................................................................................. I

Innovation and Excellence: Changing to Prevail The Brazilian Cardiovascular Surgery Inovação e Excelência: Transformando para Prevalecer a Cirurgia Cardiovascular Brasileira Walter J. Gomes.....................................................................................................................................................................................III

Three-dimensional ultrasound STIC-HDlive rendering: new technique to assessing of fetal heart Ultrassonografia tridimensional STIC-HDlive no modo de superfície: nova técnica para avaliação do coração fetal Edward Araujo Jr.....................................................................................................................................................................................V

Does beta-blocker preoperatively provides cardioprotection in myocardial revascularization? Betabloqueador pré-operatório confere cardioproteção em revascularização do miocárdio? Bruno da Costa Rocha.........................................................................................................................................................................VIII

ORIGINAL ARTICLES/ARTIGOS ORIGINAIS 1494 Repair of aortic root in patients with aneurysm or dissection: comparing the outcomes of valvesparing root replacement with those from the Bentall procedure Reparação de raiz aórtica em pacientes com aneurisma ou dissecção: comparando os resultados da técnica de substituição valvesparing com os da operação de Bentall Edvard Skripochnik, Robert E. Michler, Viktoria Hentschel, Siyamek Neragi-Miandoab..................................................................435 1495 Incidence of stroke and acute renal failure in patients of postoperative atrial fibrillation after myocardial revascularization Incidência de acidente vascular encefálico e insuficiência renal aguda em pacientes com fibrilação atrial no pós-operatório de cirurgia de revascularização do miocárdio Lucas Regatieri Barbieri, Marcelo Luiz Peixoto Sobral, Glaucio Mauren da Silva Gerônimo, Gilmar Geraldo dos Santos, Evandro Sbaraíni, Fabio Kirsner Dorfman, Noedir Antônio Groppo Stolf........................................................................................................442 1496 Myocardial protection with prophylactic oral metoprolol during coronary artery bypass grafting surgery: evaluation by troponin I. Proteção cardíaca com uso profilático de betabloqueador oral em cirurgia de revascularização miocárdica: avaliação pela troponina I. João Manoel Rossi Neto, Carlos Gun, Rui Fernando Ramos, Antonio Flavio Sanchez de Almeida, Mario Issa, Vivian Lener Amato, Jarbas J. Dinkhuysen, Leopoldo Soares Piegas....................................................................................................................................449 1497 Pressure support-ventilation versus spontaneous breathing with “T-Tube” for interrupting the ventilation after cardiac operations Pressão de suporte ventilatório versus respiração espontânea em “Tubo-T” para a interrupção da ventilação após as operações cardíacas Isabela Scali Lourenço, Aline Marques Franco, Solange Bassetto, Alfredo José Rodrigues..............................................................455

1498 Laser Doppler anemometry measurements of steady flow through two bi-leaflet prosthetic heart valves Velocimetria laser de escoamento permanente através de duas próteses cardíacas de duplo folheto Ovandir Bazan, Jayme Pinto Ortiz, Francisco Ubaldo Vieira Junior, Reinaldo Wilson Vieira, Nilson Antunes, Fabio Bittencourt Dutra Tabacow, Eduardo Tavares Costa, Orlando Petrucci Junior.................................................................................................................462 1499 Results of medium-term survival in patients undergoing cardiac transplantation: institutional experience Resultados de sobrevida a médio prazo em pacientes submetidos ao transplante cardíaco: experiência de uma instituição Ires Lopes Custódio, Francisca Elisângela Teixeira Lima, Marcos Venícios de Oliveira Lopes, Viviane Martins da Silva, João David Santos Neto, Maria do Perpétuo Socorro Martins, Samya Coutinho de Oliveira................................................................................470 1500 Fetal heart assessment in the first trimester of pregnancy: influence of crown-rump length and maternal body mass index Avaliação do coração fetal no primeiro trimestre de gestação: influência do comprimento cabeça-nádega e índice de massa corporal materna David Baptista Silva Pares, Angélia Iara Felipe Lima, Edward Araujo Júnior, Luciano Marcondes Machado Nardozza, Wellinton P. Martins, Antônio Fernandes Moron.....................................................................................................................................................477 1501 Reversible pulmonary trunk banding. IX. G6PD activity of adult goat myocardium submitted to ventricular retraining Bandagem ajustável do tronco pulmonar. IX: atividade da G6PD do miocárdio de cabras adultas submetido ao treinamento ventricular Renato Samy Assad, Leonardo Augusto Miana, Miriam Helena Fonseca-Alaniz, Maria Cristina Donadio Abduch, Gustavo José Justo da Silva, Fernanda Santos de Oliveira, Luiz Felipe Pinho Moreira, José Eduardo Krieger................................................................482 1502 Depression after CABG: a prospective study Depressão após revascularização do miocárdio: um estudo prospectivo Joana Kátya Veras Rodrigues Sampaio Nunes, José Albuquerque de Figueiredo Neto, Rosângela Maria Lopes de Sousa, Vera Lívia Xavier de Castro Costa, Flor de Maria Araújo Mendonça Silva, Ana Flávia Lima Teles da Hora, Edna Lúcia Coutinho da Silva, Lívia Mariane Castelo Branco Reis...............................................................................................................................................................491 1503 Twenty four hour imaging delay improves viability detection by Tl-201 myocardial perfusion scintigraphy Atraso de imagem de 24 horas melhora a viabilidade de detecção por cintilografia de perfusão miocárdica Tl-201 Zehra Pınar Koç, Tansel Ansal Balcı, Necati Dağlı............................................................................................................................498 1504 Indicators of surgical treatment of patent ductus arteriosus in preterm neonates in the first week of life Indicadores para o tratamento cirúrgico na persistência do ducto arterial em neonatos prematuros na primeira semana de vida Renato Braulio, Cláudio Léo Gelape, Fátima Derlene da Rocha Araújo, Kelly Nascimento Brandão, Luciana Drummond Guimarães Abreu, Paulo Henrique Nogueira Costa, Flávio Diniz Capanema.......................................................................................................504 1505 Mortality risk is dose-dependent on the number of packed red blood cell transfused after coronary artery bypass graft Risco de mortalidade é dose-dependente do número de unidades de concentrado de hemácias transfundidas após cirurgia de revascularização miocárdica Antônio Alceu dos Santos, Alexandre Gonçalves Sousa, Raquel Ferrari Piotto, Juan Carlos Montano Pedroso...............................509 1506 Association of pre and intraoperative variables with postoperative complications in coronary artery bypass graft surgery Associação de variáveis pré e intraoperatórias com complicações pós-operatórias em cirurgia de revascularização do miocárdio Camila Gimenes, Silvia Regina Barrile, Bruno Martinelli, Carlos Fernando Ronchi, Eduardo Aguilar Arca, Rodrigo Gimenes, Marina Politi Okoshi, Katashi Okoshi..............................................................................................................................................................518 EXPERIMENTAL WORK/TRABALHO EXPERIMENTAL 1507 Development of cardioplegic solution without potassium: experimental study in rat Desenvolvimento de solução cardioplégica sem potássio: estudo experimental em ratos Karla Reichert, Helison Rafael Pereira do Carmo, Fany Lima, Anali Galluce Torina, Karlos Alexandre de Souza Vilarinho, Pedro Paulo Martins de Oliveira, Lindemberg Mota Silveira Filho, Elaine Soraya Barbosa de Oliveira Severino, Orlando Petrucci...................524 REVIEW ARTICLES/ARTIGOS DE REVISÃO 1508 On-pump versus off-pump coronary artery bypass graft surgery. What do the evidence show? Revascularização cirúrgica do miocárdio com versus sem circulação extracorpórea. O que mostram as evidências? Alfredo José Rodrigues, Paulo Roberto Barbosa Évora, Paulo Victor Alves Tubino..........................................................................531

1509 Nursing assistance at the hospital discharge after cardiac surgery: integrative review Assistência de enfermagem na alta hospitalar em pós-operatório de cirurgia cardíaca: revisão integrativa Daniela Fraga de Jesus, Patrícia Figueiredo Marques.........................................................................................................................538 SHORT COMMUNICATION/COMUNICAÇÃO BREVE 1510 Supravalvular aortic stenosis in adult with anomalies of aortic arch vessels and aortic regurgitation Estenose aórtica supravalvar em adulto com anomalia de vasos da base e insuficiência aórtica Acrisio Sales Valente, Polyanna Alencar, Alana Neiva Santos, Roberto Augusto de Mesquita Lobo, Fernando Antônio de Mesquita, Aloyra Guedis Guimarães....................................................................................................................................................................545 HOW TO DO IT/COMO EU FAÇO 1511

Use of a stent-graft and vascular occlude to treat primary and re-entry tears in a patient with a Stanford type B aortic dissection O uso de endoprótese e oclusor vascular para tratar ruptura primária e de re-entrada em paciente com dissecção aórtica tipo B de Stanford Huihua Shi, Min Lu, Mier Jiang..........................................................................................................................................................550

IMAGES IN CARDIOVASCULAR SURGERY/IMAGENS EM CIRURGIA CARDIOVASCULAR 1512 Terminal right coronary artery fistula to right ventricle Fístula terminal da artéria coronária direita para o ventrículo direito Paulo Evora, Solange Basseto, Alfredo J Rodrigues............................................................................................................................555 POINT OF VIEW/PONTO DE VISTA 1513 Words to the young cardiovascular surgeon Palavras ao jovem cirurgião cardiovascular Luis Alberto O. Dallan.........................................................................................................................................................................556 Erratum/Errata......................................................................................................................................................................................559

Abstracts of 13th Congress of SCICVESP (Society of Cardiovascular Surgery of São Paulo) Resumos dos trabalhos apresentados no 13º Congresso da SCICVESP (Sociedade de Cirurgia Cardiovascular do Estado de São Paulo) ..................................................................................................................................................................... 560

Reviewers BJCVS 28.4/Revisores RBCCV 28.4.................................................................................................................................573

Impresso no Brasil Printed in Brazil

Grafic design and layout: Heber Janes Ferreira

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY E-mail: revista@sbccv.org.br Sites: www.scielo.br/rbccv www.rbccv.org.br

Editorial

Animal research and cardiovascular surgery Pesquisa com animais e a cirurgia cardiovascular

Domingo M. Braile* DOI: 10.5935/1678-9741.20130068

T

he invasion of the Royal Institute in São Roque, SP, on the 18th of October, in which tens of Beagle dogs were evacuated by activists, created a huge controversy, amplified by the wide dissemination in the media and on the internet. Moreover, the action of activists led to the closure of the lab. Not only that. Many institutions that use animals as experimental models have suffered threats and pressures, being forced to halt their work. In many institutions, educational activities and training of residents who use animals are being progressively replaced by simulations and experiments with pig hearts obtained from slaughterhouses. It is a situation that merits consideration by all. As “scientists” surgeons we are, we are required to examine this issue from a objective point of view, without the emotional tone of people driven by passion and irrationality. This “activism” is not restricted to Brazil. In Italy, under pressure from activists, a law barring animal research adopted by parliament and awaiting presidential approval has been criticized by scientists. A petition calling for the revision of the law had succeeded, until the beginning of December, 13,000 accessions. According to this law, from 2017, it is prohibited the use of animals for research, experiments relating to drug abuse and xenotransplantation. It also prohibits the breeding of dogs, cats and non-human primates for scientific purposes, although the Ministry of Health may authorize its use for basic research aimed at the treatment of serious human and animals diseases. Finally, it ends with the use of animals in university courses in sciences, medicine included, with the exception of veterinary. The use of animals in scientific research dates back centuries. Cardiovascular surgery, specifically, owes much to the animal research to get to the current stage, saving millions of lives around the planet. Pioneers like Clarence Dennis, John Gibbon, Walton Lillehei, among dozens of others in the midtwentieth century, used dogs to develop CPB [1]. The Brazilian Journal of Cardiovascular Surgery (BJCVS) has regularly published articles reporting animal research. In this edition, the article “Reversible pulmonary trunk banding. IX. G6PD activity of adult goat myocardium submitted to ventricular retraining” by Renato Assad and colleagues (p. 482), is an example to use goats to measure

myocardial activity of glucose 6-phosphate dehydrogenase. The BJCVS maintains its commitment to ethics when explaining in its Rules for Authors that: “In experimental studies involving animals, it must be in compliance with the standards set out in Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, National Academy of Sciences, Washington, DC, United States), 1996, and Ethical Principles in Animal Experimentation (Brazilian College of Animal Experimentation - COBEA, available at: www.cobea.org.br), 1991”. There is also the requirement of submission of a copy of the opinion of the Research Ethics Committee when submitting the manuscript and empowering research. It is a way of ensuring that standards are being met . Remember that morality, ethics and laws are representing the desire of the majority and must be respected. Citations I’ve received with much satisfaction, an email from Dr. Antonio Alceu dos Santos, stating that the “Heart retransplantation in children without the use of blood product” published in Volume 27.2 of BJCVS, of which he is the first author, was one of the “top 20” in the field of pediatric cardiac surgery, according to the site search BioMedLib (www.biomedlib.com). This shows that the internationalization of our journal is a reality. I have emphasized that through our site (www.bjcvs.org and www.scielo.br/ rbccv) are accessed in over 100 countries, about 7000 readers daily. Therefore, I insist on the necessity of the study have high scientific standard and preferably written in English, so that the hits on our sites can turn into citations, the only way to increase our Impact Factor. In this issue, we publish a study - epair of aortic root in patients with aneurysm or dissection: comparing the outcomes of valvesparing root replacement with those from the Bentall procedure (p. 435), from United States. It is a proof that we are reaching our goals and gives us more confidence to move forward with the unconditional support we have received from colleagues. APP We have expanded the platforms on which BJCVS can be

I

Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg

after myocardial revascularization” (pág. 442); “Results of medium-term survival in patients undergoing cardiac transplantation: institutional experience” (pág. 470); “Depression after CABG: a prospective study” (pág. 491); e “Mortality risk is dose-dependent on the number of packed red blood cell transfused after coronary artery bypass graft”” (page. 509). I thank all who have contributed to BJCVS maintain its standard of excellence in 2013. Members and Board of BSCVS, Editorial Board of BJCVS, Advertisers and colleagues from various specialties who provided us with their great articles. Thank you all for the invaluable collaboration and trust vested in me. My warmest regards and my wishes that Christmas renew all our hopes and 2014 be prodigal in achievements.

accessed. Our application for smartphones and tablets is now available in the Google Store. The application for the devices that use the iOS system is being finalized and soon it will also may be downloaded. XML I remind the readers that from 2014, we will have to adapt to the new quality standards by SciELO, which will require that publications adopt the XML standard, the same used by Thomson Reuters and the PubMed Central database for which we are seeking our entrance. Therefore, I ask that everyone follow the pattern established by norms of BJCVS, especially with regard to images. Our team is available to answer any questions. BSCVS I must compliment the current Board of the Brazilian Society of Cardiovascular Surgery (BSCVS), led by president Prof. Dr. Walter Gomes, terminating his mandate. Many were the achievements for our specialty, in addition to the unconditional support to BJCVS. On page III, Dr. Walter sums up his management. Also, I take this opportunity to welcome the new board, captained by Dr. Marcelo Matos Cascudo, which certainly will pursue such work.

Domingo M. Braile Editor-in- Chief BJCVS

CME Items available for testing by the Continuing Medical Education (CME) system are: “Incidence of stroke and acute renal failure in patients of postoperative atrial fibrillation

REFERENCE 1. Braile DM, Godoy MF. História da cirurgia cardíaca no mundo. Rev Bras Cir Cardiovasc. 2012;27(1):125-36.

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Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg

Editorial

Innovation and Excellence: Changing to Prevail the Brazilian Cardiovascular Surgery Inovação e Excelência: Transformando para Prevalecer A Cirurgia Cardiovascular Brasileira

Walter J. Gomes1 DOI: 10.5935/1678-9741.20130069

Labor omnia vincit – Work conquers all Prof. Dr. Euryclides de Jesus Zerbini

of the largest national events of this specialty in the world. The newly incorporated multi-professional modules, such as the Perfusion, Nursing, and Physiotherapy in Cardiovascular Surgery Symposiums, have provided the opportunity to gather every professional involved in caring for cardiovascular patients in one place, allowing their conduct to be updated and unified. The inclusion of the Academic Congress in Cardiovascular Surgery aims to attract the new generation, to gather, inform, and form what will be the future of this Specialty as well as to motivate the creation of new Cardiovascular Surgery Interest Groups throughout the country. The new Hands-on practical module, directed by Prof. Gilberto Barbosa, has been a great success due to its straightforward, practical, and educational format. Success today is contingent on building partnerships and joining efforts. Since the industry holds the technology we need to continue providing the best care for our patients, the SBCCV has strengthened those ties, in a fully ethical and transparent manner. By incorporating new technologies, innovative surgical techniques and implantable devices have widened the scope of the cardiovascular surgeon practice. Therefore, training partnerships are necessary to acquire the abilities and expertise needed to ensure excellent results. Besides training, these programs offer medical education, access to scientific information, and, subsequently, multicenter trials which will have to include Brazil. In addition, the training benefits residents and perfusionists. There is a need to focus on scientific advances. Partnerships with international societies and the industry have helped, but they need to advance faster. In addition, university involvement in scientific contributions should be emphasized in order to

Following in the footsteps of our predecessors, the Brazilian Society of Cardiovascular Surgery (SBCCV) has persevered in its quest for excellence, becoming a role model for other Specialty Societies due to its achievements and the progress it has made in both the public and the private sector. However, there are still some great challenges ahead which will be faced and overcome with the usual determination and resilience as well as the spirit of unity, cohesion, and harmony that are characteristic of the cardiovascular surgery community. Technological and scientific advances and innovations have refreshed our specialty and placed cardiovascular surgery in the spotlight once again. Those achievements in all areas have enabled us to plan farther and reach greater heights. The insertion of Brazil amongst developed nations was consolidated through the process of internationalization. Partnerships with the European Association for Cardiothoracic Surgery (EACTS) and the Sociedad Latinoamericana de Cirugía Cardiovascular y Torácica (SLCCT) have allowed us to strengthen the scientific base of our Congress, counting on the presence and interaction of the most respected surgeons from every corner of the world. Several subject matters are currently being negotiated, such as a Continuing Education course, exchange of surgeons and residents, joint symposiums, multicenter studies, cooperation of scientific journals, among others. Recently, a partnership has been extended to the American Association for Thoracic Surgery (AATS). The SBCCV Congress has continuously grown in number of participants as well as exhibitors, being recognized as one

1 – President of the Brazilian Society of Cardiovascular Surgery (SBCCV)

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bring accumulated knowledge to cardiovascular surgeons spread throughout a country of continental dimensions with different regional realities. At the moment, following the examples of the United States and Canada, it is mandatory to restructure the Cardiovascular Surgery Training Program by abolishing the previous full requirement of General Surgery and giving greater emphasis to scientific training, research, and writing of scientific articles. Besides training good surgeons, it is imperative to train researchers in order to continue developing this specialty. Institutional partnerships have been fruitful, with the SBCCV working in harmony and with the same objectives to develop joint projects with the Brazilian Society of Cardiology (SBC), the Brazilian Medical Association (AMB), the Heart Failure Department of the SBC (DEIC), the Brazilian Association of Intensive Medicine (AMIB), the Brazilian Society of Hemodynamics and Interventional Cardiology (SBHCI), and the Brazilian Society of Pediatrics (SBP), among others. This type of work emphasizes the sharing of knowledge and experience across specialties so that the patient is offered the best therapeutic decisions with the greatest benefits. To this end, the multidisciplinary approach (the Heart Team) is encouraged by specialty societies and, in particular, by the SBCCV. In addition, the SBCCV has also made efforts to work in collaboration with government agencies, such as ANVISA, in the Technical Chamber of Drugs; the Ministry of Education, in the Federal University Teaching Hospitals Project; and the Ministry of Health, in the following projects: advice on orthosis and prosthesis; the National Registry of Cardiovascular Surgery; and the National Program for the Surgical Treatment of Children with Congenital Heart Disease, which aims to reduce high mortality rates due to lack of access to surgical treatment. The meetings have focused on a range of issues: the need to implement a list of sequential procedures to be paid by SUS, as previously agreed; the review of the codes in the SUS list; the inclusion of new devices and materials for cardiovascular surgery in the SUS; and the challenges of pediatric cardiovascular surgeries in Brazil, where the number of procedures is insufficient, leaving two-thirds of the patients in need without surgical treatment. Our scientific journal, the Brazilian Journal of Cardiovascular Surgery (BJCVS), under the editorship of Prof. Dr. Domingo Braile, earned a higher impact factor, reflecting the capability and the quality of the production of Brazilian cardiovascular surgeons. The Scientific Bulletin

keeps cardiovascular surgeons updated by selecting the best papers published in the given period thus contributing to better decision-making in the treatment of patients. Since the goals of the SBCCV have come closer to those of their members, it has reinforced the need to defend the professional dignity of cardiovascular surgeons applying fair fees by continuing to support the negotiations with private payers. Unity has been our strength, our biggest triumph. Surgeons no longer see their colleagues as competitors, but as allies in the struggle to regain professional dignity. The National Registry of Cardiovascular Surgery is being implemented and it will place us on an equal footing with other specialty societies worldwide as well as Europe, the United States, and Japan. It will allow us to understand our reality and provide subsidies to improve the quality of our results. We also have a new home! The recent acquisition of much larger premises to fit the growth SBCCV experienced in the last few years will allow us to better match demands. Furthermore, it will make more resources available for training and continuing education, with an area for the Hands-on training and an auditorium with capacity for 40 people. There is also recognition for the teamwork that produced the results described above. All these accomplishments and achievements would not have been possible without the hard work, idealism, and enthusiasm of dedicated individuals, members of the Board and of our community, who contributed to every single part of this report by letting collective interests prevail over their own. Throughout these years of involvement, we have had the opportunity to live with, admire, and learn from the work of those individuals who have made the SBCCV stronger, more robust, and more respected. We have learned from their ideas, prominent views and wisdom, and we have accumulated experience in dealing with antagonisms and controversies, solving conflicts, and shaping new leaders. Finally, I would like to express my appreciation for the honor of being president of the SBCCV. In this term, marked by several trips, conversations and exchanges of information, I have learned to respect and admire even more the cardiovascular surgeons scattered around the country, who not only work many times in adverse conditions without overlooking patient care and their responsibility or shirking long shifts, day and night, but who also do this job with an incredible amount of love, dedication, and passion to their profession and their patients. I believe this is what makes cardiovascular surgeons stand out from the rest.

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Editorial

Three-dimensional ultrasound STIC-HDlive rendering: new technique to assessing of fetal heart Ultrassonografia tridimensional STIC-HDlive no modo de superfície: nova técnica para avaliação do coração fetal

Edward Araujo Júnior1, MD, MSc, PhD; Luciano Marcondes Machado Nardozza1, MD, MSc, PhD; Antonio Fernandes Moron1, MD, MSc, PhD DOI: 10.5935/1678-9741.20130070

Congenital heart diseases (CHD) are the most common fetal congenital malformations, corresponding to an incidence six higher than chromosome anomalies and four higher than neural tube defects [1]. The prevalence of CHD in newborns ranges from 0.6% to 5% [2]. It’s too known that the prenatal diagnosis can modify the outcome of some types of CHD [3,4]. The two-dimensional echocardiography is the “gold standard” exam to the diagnosis of CHD; however, it is operator-depending and only is realized in high risk pregnancies [5]. Although, the majority of CHD cases occurring in low risk pregnancies [6], being necessary appropriate screening in the second trimester ultrasound scan. Due the high incidence of CDH in low risk pregnancies, several international associations tried to incorporate the “extended basic” cardiac scan in the second trimester ultrasound exam. In other words, the “extended basic” would be the inclusion of ventricles outflows in the four chamber view [7,8]. The incorporation of medical ultrasound obstetrics education has proved to be an effective method to improve the detection rate of CHD [9]. Despite of these improvements in the fetal cardiac screening, the second trimester ultrasound scan continues being operator-depending and time-consuming. In the begging of 2000, a new software named spatio-temporal image correlation (STIC) has been available in several three-dimensional ultrasound machines. STIC enables acquisition of fetal heart volume and vascular connection data. The images generated by this software can be evaluated both in multiplanar and in rendering modes. They can also be evaluated both statically and in movement (4D) through a cineloop sequence that simulates an entire cardiac cycle [10,11]. The advantages of STIC for fetal heart evaluation are the following: lower dependency on the operator’s experience, in obtaining diagnostic planes; shorter time taken to perform

the examination, without the patient’s presence during the volume analysis; possibility of evaluating structures through the render mode with assessment of their morphology and function [12]; and the capacity to send volumes for analysis at other fetal cardiology reference centers via an internet link [13]. Nowadays, the STIC has been utilized in the rendering mode to assess the atrioventricular valves [14,15] and interventricular septum [16]. STIC and virtual-organ computer-aided analysis (VOCAL) has been used to assess the fetal cardiac function by means heart stroke, cardiac output and ejection fraction [17,18]. In relation to screening of CHD, the isolated use of STIC still remains controversial. Some studies have shown advantages of two-echocardiography under STIC in the screening of CHD [19,20]; however, one study showed a great accuracy of STIC in the diagnosis of CHD in a high risk pregnancies [21]. Its necessary new multicenter studies with large samples both low and high risk obtaining definitive results [22]. Recently, a new software named HDlive has been available in Voluson E8 (General Electric Medical System, Zipf, Austria) ultrasound machine. HDlive is a new technique of surface designs, in which the operator performs light settings, creating depth effects by means of adequate lighting and shading of the images [23]. HDlive has been used in the assessment of normal development of embryo/fetus [24,25] as well as in several cases of fetal malformations [26,27]. The STIC-HDlive rendering is a new algorithm to assess the fetal heart structures similarly to other fetal structures. This new algorithm permits to assess the standard fetal echocardiography views as the four chamber and ventricles outflow views (Figure 1). Furthermore, this technique permits to reconstruction of all fetal heart and your connections (Figure 2). Recent study assessed four normal and three abnormal fetal hearts (Ebstein’s anomaly, hypoplastic left heart syndrome and tetralogy of Fallot) [28]. The authors refer that STIC-HDlive permitted realistic sensations of each leaflet of the atrioventricular valves. In the case of Ebstein’s anomaly, natural and ana-

Universidade Federal de São Paulo, Department of Obstetrics (UNIFESP), São Paulo, SP, Brazil. E-mail: araujojred@terra.com.br 1

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differs from conventional rendering methods because it uses a fixed virtual light source that calculates the propagation of light through skin and tissue. Operators can freely select the light source at any angle relative to the ultrasound volume to enhance anatomical details [29]. In summary, we present a new technique named STICHDlive to the assessing of fetal heart structures. The realistic images provided by this algorithm open new perspectives of non-invasive fetal cardiology, permitting to study in details valves, interventricular septum and venous/arterial connections. New studies comparing the HDlive and conventional three-dimensional rendering modes are necessary to prove the real application of STIC-HDlive in fetal echocardiography.

Abbreviations, acronyms & symbols CHD Congenital heart diseases STIC Spatio-temporal image correlation VOCAL Virtual-organ computer-aided analysis

tomically realistic images of significantly low attachment of the tricuspid valve and the atrialized portion of the right ventricle obtained. In the case of hypoplastic left heart syndrome, thickened tricuspid and dysplastic pulmonary valves were clearly revealed. In the case of tetralogy of Fallot, the overriding aorta and ventricular septal defect were realistically depicted [28]. In other article, the authors have made the reconstruction of normal fetal heart showing the four chamber view and the left ventricle and descending aorta. The authors refer that the HDlive

REFERENCES

1. Carvalho JS, Mavrides E, Shinebourne EA, Campbell S, Thilaganathan B. Improving the effectiveness of routine prenatal screening for major congenital heart defects. Heart. 2002;88(4):387-91. 2. Grandjean H, Larroque D, Levi S. The performance of routine ultrasonographic screening of pregnancies in the Eurofetus Study. Am J Obstet Gynecol. 1999;181(2):446-54. 3. Bonnet D, Coltri A, Butera G, Fermont L, Le Bidois J, Kachaner J, et al. Detection of transposition of the great arteries in fetuses reduces neonatal morbidity and mortality. Circulation. 1999;99(7):916-8. 4. Tworetzky W, McElhinney DB, Reddy VM, Brook MM, Hanley FL, Silverman NH. Improved surgical outcome after fetal diagnosis of hypoplastic left heart syndrome. Circulation. 2001;103(9):1269-73.

Fig. 1 - STIC-HDlive rendering showing the reconstruction of fetal heart in the four-chamber view

5. Allan L. Prenatal diagnosis of structural cardiac defects. Am J Med Genet C Semin Med Genet. 2007;145C(1):73-6. 6. Strumpflen I, Strumpflen A, Wimmer M, Bernaschek G. Effect of detailed fetal echocardiography as part of routine prenatal ultrasonographic screening on detection of congenital heart disease. Lancet. 1996;348(9031):854-7. 7. International Society of Ultrasound in Obstetrics & Gynecology. Cardiac screening examination of the fetus: guidelines for performing the ‘basic’ and ‘extended basic’ cardiac scan. Ultrasound Obstet Gynecol. 2006;27(1):107-13. 8. Fetal Echocardiography Task Force; American Institute of Ultrasound in Medicine Clinical Standards Committee; American College of Obstetricians and Gynecologists; Society for Maternal-Fetal Medicine. AIUM practice

Fig. 2 - STIC-HDlive rendering showing the reconstruction of fetal heart and its vascular connections

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guideline for the performance of fetal echocardiography. J Ultrasound Med. 2011;30(1):127-36.

18. Simioni C, Araujo Júnior E, Martins WP, Rolo LC, Rocha LA, Nardozza LM, et al. Fetal cardiac output and ejection fraction by spatio-temporal image correlation (STIC): comparison between male and female fetuses. Rev Bras Cir Cardiovasc. 2012;27(2):275-82.

9. Asplin N, Dellgren A, Conner P. Education in obstetrical ultrasound: an important factor for increasing the prenatal detection of congenital heart disease. Acta Obstet Gynecol Scand. 2013;92(7):4-8.

19. Wanitpongpan P, Kanagawa T, Kinugasa Y, Kimura T. Spatio-temporal image correlation (STIC) used by general obstetricians is marginally clinically effective compared to 2D fetal echocardiography scanning by experts. Prenat Diagn. 2008;28(10):923-8.

10. Gonçalves LF, Lee W, Chaiworapongsa T, Espinoza J, Schoen ML, Falkensammer P, et al. Four-dimensional ultrasonography of the fetal heart with spatiotemporal image correlation. Am J Obstet Gynecol. 2003;189(6):1792-802.

20. Cohen L, Mangers K, Platt L, Julien S, Gotteiner N, Dungan J, et al. Quality of 2- and 3-dimensional fast acquisition fetal cardiac imaging at 18 to 22 weeks: ramifications for screening. J Ultrasound Med. 2009;28(5):595-601.

11. DeVore GR, Falkensammer P, Sklansky MS, Platt LD. Spatio-temporal image correlation (STIC): new technology for evaluation of the fetal heart. Ultrasound Obstet Gynecol. 2003;22(4):380-7.

21. Bennasar M, Martinez JM, Gomez O, Bartrons J, Olivella A, Puerto B, et al. Accuracy of four-dimensional spatiotemporal image correlation echocardiography in the prenatal diagnosis of congenital heart defects. Ultrasound Obstet Gynecol. 2010;36(4):458-64.

12. Vinãls F, Poblete P, Giuliano A. Spatio-temporal image correlation (STIC): a new tool for the prenatal screening of congenital heart defects. Ultrasound Obstet Gynecol. 2003;22(4):388-94.

22. Araujo Júnior E, Rolo LC, Nardozza LM, Moron AF. Fetal cardiac evaluation by 3D/4D ultrasonography (STIC): what is its real applicability in the diagnosis of congenital heart disease? Rev Bras Cir Cardiovasc. 2013;28(1):III-V.

13. Vinãls F, Mandujano L, Vargas G, Giuliano A. Prenatal diagnosis of congenital heart disease using fourdimensional spatio-temporal image correlation (STIC) telemedicine via an Internet link: a pilot study. Ultrasound Obstet Gynecol. 2005;25(1):25-31.

23. Kagan KO, Pintoffl K, Hoopmann M. First-trimester ultrasound images using HDlive. Ultrasound Obstet Gynecol. 2011;38(5):607.

14. Rolo LC, Nardozza LM, Araujo Júnior E, Hatanaka AR, Rocha LA, Simioni C, et al. Reference ranges of atrioventricular valve areas by means of four-dimensional ultrasonography using spatiotemporal image correlation in the rendering mode. Prenat Diagn. 2013;33(1):50-5.

24. Hata T. HDlive rendering image at 6 weeks of gestation. J Med Ultrasonics. 2013 [ahead of print]. 25. Merz E. Surface reconstruction of a fetus (28 + 2 GW) using HDlive technology. Ultraschall Med. 2012;33(3):211.

15. Araujo Júnior E, Rolo LC, Simioni C, Nardozza LM, Rocha LA, Martins WP, et al. Comparison between multiplanar and rendering modes in the assessment of fetal atrioventricular valve areas by 3D/4D ultrasonography. Rev Bras Cir Cardiovasc. 2012;27(3):472-6.

26. Hata T, Hanaoka U, Tenkumo C, Ito M, Uketa E, Mori N, et al. Three-dimensional HDlive rendering image of cystic hygroma. J Med Ultrasonics. 2013;40(3):297-9.

16. Nardozza LM, Rolo LC, Araujo Júnior E, Hatanaka AR, Rocha LA, Simioni C, et al. Reference range for fetal interventricular septum area by means of four-dimensional ultrasonography using spatiotemporal image correlation. Fetal Diagn Ther. 2013;33(2):110-5.

27. Tenkumo C, Tanaka H, Ito T, Uketa E, Morin N, Hanaoka U, et al. Three-dimensional HDlive rendering images of the TRAP sequence in the first trimester: reverse end-diastolic umbilical artery velocity in a pump twin with an adverse pregnancy outcome. J Med Ultrasonics. 2013;40(3):293-6.

17. Simioni C, Nardozza LM, Araujo Júnior E, Rolo LC, Zamith M, Caetano AC, et al. Heart stroke volume, cardiac output, and ejection fraction in 265 normal fetus in the second half of gestation assessed by 4D ultrasound using spatio-temporal image correlation. J Matern Fetal Neonatal Med. 2011;24(9):1159-67.

28. Hata T, Mashima M, Ito M, Uketa E, Mori N, Ishimura M. Three-dimensional HDlive rendering images of the fetal heart. Ultrasound Med Biol. 2013;39(8):1513-7. 29. Grisolia G, Tonni G. Fetal echocardiography using HDlive. J Obstet Gynecol Can. 2013;35(6):497-8.

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Editorial

Does preoperative beta-blocker offer myocardial protection during coronary artery bypass grafting? Betabloqueador pré-operatório confere cardioproteção em revascularização do miocárdio?

Bruno da Costa Rocha1, MD, PhD

DOI: 10.5935/1678-9741.20130071

The past two decades have seen a number of studies being carried out in order to investigate the use of beta-blockers as myocardial protection in patients who undergo great surgical stress and are under significant risk factors, especially in noncardiovascular surgery regarding major adverse cardiac events (MACE) and death [1,2]. During meta-analysis published in 2010, which included the patient profile described above, Angeli et al. [3] showed that the use of beta-blockers did not have an impact on mortality (odds ratio [OR] 1.15; confidence interval [CI] of 0.92-1.43; P = 0.2717). Despite meta-analytical rigor, the heterogeneity of the clinical trials included in the study make it difficult to undertake a detailed analysis, mainly as a result of the large range of surgical procedures and risk factors. Stevens et al. [4] stated that the prophylactic use of beta-blockers in high risk patients who underwent major surgery showed, in a series of clinical trials, variation in the number needed to treat (NNT) ranging from 2.5 to 8.3; whereas studies with lower hierarchy showed NNT of 32 to reduce mortality. That being said, the guidelines of both North American associations for cardiology, “Joint American College of Cardiology” and “American Heart Association”, recommend the use of beta-blockers in patients with confirmed myocardial ischemia (Class I, LOE B) and in other high risk patients (class IIa, LOE B) undergoing non-cardiovascular surgery [5]. Note that the guidelines were published in 2007, before the 2008 POISE study, which included 8350 patients randomized to receive metoprolol succinate in the preoperative period and up to 30 days after non-cardiac surgery [6]. The results showed that 176 patients (4.2%) from the metoprolol group developed acute myocardial infarction (AMI) versus 239

1. Cirurgião Cardiovascular. Cirurgião Associado do MSF-Médicos Sem Fronteiras. Fellowship em CCV Pediátrica- Necker-França

(5.7%) from the control group; Hazard Ratio (HR) of 0.73 (0.60-0.89: P=0.0017). However, the metoprolol group had higher mortality and cerebral ischemia than the control group, 3.1% versus 2.3%; HR 1.33 (1.03-1.74: P=0.0317) and 1.0% versus 0.5%; HR 2.17 (1.26-3.74: P=0.0053), respectively. On the other hand, the use of beta-blockers for acute ST segment elevation myocardial infarction is well established (class I, LOE A). There is a scientific gap as far as myocardial protection offered by beta-blockers in patients who underwent cardiovascular surgery is concerned, especially in the surgical treatment of coronary disease. SEE ORIGINAL ARTICLE ON PAGES 449-454 In the 1990s, Mair et al. [7] described the characteristics of Troponin I (TnI) and Troponin T distribution after myocardial lesions, peak plasma concentrations (up to 12 hours), and TnI specificity for cardiac muscle apoptosis. Antman et al. [8], in a multicenter study, evaluated TnI values in 1440 people with angina pectoris. Out of the 1440, 573 patients, with serum TnI levels above 0.4 ng/ml, had higher mortality in 42 days of follow-up. The study showed that, quantitatively, there is a strong correlation between higher serum TnI levels and death as the outcome. Subsequently, in Brazil, Leal et al. [9] analyzed serum TnI levels in patients who had undergone myocardial revascularization. In that study, the authors found there was correlation between the quantitative value of TnI measured by chemiluminescence whenever it was above 2.5 ng/ml on the first postoperative day and increased mortality in 30% to 50% in the first six months after surgery. In the present issue, considering the assumptions set forth above, the authors describe a randomized clinical trial based on the following questions [10]: 1. Does the use of beta-blockers introduced 72 hours before coronary artery bypass grafting surgery alter serum TnI levels in the postoperative period?

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2. Are there secondary changes to cardiovascular, morbidity, and mortality outcomes? In order to answer the first question, despite the small sample size (68 patients), in terms of low incidence outcomes, the authors showed that, using the immunometric method, TnI concentrations were “…lower in group B than in group A (2.5 ng/ml versus 3.7 ng/ml, P<0.05)”. Patients in Group B were administered 200 mg/day metoprolol tartrate in the preoperative period and Group A was the control. There was no statistically significant difference between the groups in terms of clinical outcomes (see Table 6 – page 452). There was also acute atrial fibrillation in three patients from Group A and one patient from Group B (P=0.27). In addition, average baseline heart rate was 73.8 bpm ± 1.7 in Group A, higher than the average in Group B, which was 68.0 bpm ± 1.7 (P=0.021). Thus, this variable was heterogeneously distributed between groups A and B, previous randomization notwithstanding. Multivariate analysis showed there was an increase in serum Troponin I levels at 12 hours postoperative in Group A (control) compared to Group B (metoprolol). As far as the second question is concerned, the study lacked statistical power to determine differences in clinical outcomes, such as greater use of vasoactive drugs for longer than 24 hours by Group B (metoprolol) (P=0.085), likely constituting a type II error. Therefore, it is advisable not to make assumptions about the “prophylactic” use of metoprolol tartrate before CABG based on these results from clinical application. In short, subsequent studies in this interesting area can help determine the clinical impact of using beta-blockers as premedication in patients undergoing CABG and whether it is safe.

troponin <=99th centile: an observational study? Emerg Med J. 2013;30(1):15-8. 2. Auerbach AD, Goldman L. Beta-blockers and reduction of cardiac events in noncardiac surgery: clinical applications. JAMA. 2002;287(11):1445-7. 3. Angeli F, Verdecchia P, Karthikeyan G, Mazzotta G, Gentile G, Reboldi G. ß-blockers reduce mortality in patients undergoing high-risk non-cardiac surgery. Am J Cardiovasc Drugs. 2010;10(4):247-59. 4. Stevens RD, Burri H, Tramèr MR. Pharmacologic myocardial protection in patients undergoing noncardiac surgery: a quantitative systematic review. Anesth Analg. 2003;97(3):623-33. 5. Fleisher LA; American College of Cardiology/American Heart Association. Cardiac risk stratification for noncardiac surgery: update from the American College of Cardiology/American Heart Association 2007 guidelines. Cleve Clin J Med. 2009;76(Suppl 4):S9-15. 6. POISE Study Group, Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, Villar JC, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371(9627):1839-47. 7. Mair J. Cardiac troponin I and troponin T: are enzymes still relevant as cardiac markers? Clin Chim Acta. 1997;257(1):99-115. 8. Antman EM, Tanasijevic MJ, Thompson B, Schactman M, McCabe CH, Cannon CP, et al. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med. 1996;335(18):1342-9. 9. Leal JCF, Braile DM, Godoy MF, Purini Neto J, Paula Neto A, Ramin SL, et al. Avaliação imediata da troponina I cardíaca em pacientes submetidos à revascularização do miocárdio. Rev Bras Cir Cardiovasc. 1999;14(3):247-53.

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10. Rossi Neto JM, Gun C, Ramos RF, Almeida AFS, Issa M, Amato VL, et al. Myocardial protection with prophylactic oral metoprolol during coronary artery bypass grafting surgery: evaluation by troponin I. Rev Bras Cir Cardiovasc. 2013;28(4):449-54.

1. Kelly AM. What is the incidence of major adverse cardiac events in emergency department chest pain patients with a normal ECG, thrombolysis in myocardial infarction score of zero and initial

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SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY E-mail: revista@sbccv.org.br Sites: www.scielo.br/rbccv www.rbccv.org.br

Rev Bras Cir Cardiovasc 2013;28(4):435-41

Skripochnik E, et al. - Repair of aortic root in patients with aneurysm or ORIGINAL ARTICLE dissection: comparing the outcomes of valve-sparing root replacement with those from the Bentall procedure

Repair of aortic root in patients with aneurysm or dissection: comparing the outcomes of valvesparing root replacement with those from the Bentall procedure Reparação de raiz aórtica em pacientes com aneurisma ou dissecção: comparando os resultados da técnica de substituição valve-sparing com os da operação de Bentall

Edvard Skripochnik1, MD; Robert E. Michler1, MD; Viktoria Hentschel2, MD; Siyamek NeragiMiandoab1 MD, PhD

DOI: 10.5935/1678-9741.20130072

RBCCV 44205-1494

Abstract Introduction: Management of aortic root aneurysm or dissection has been the subject of much discussion that has led to some modifications. The current trend is a valve-sparing root replacement. We compared the outcome following valve sparing root repair with Bentall procedure. Methods: We retrospectively evaluated 70 patients who underwent root replacement for aneurysm or dissection and compared the outcomes of valve-sparing root replacement with those of the Bentall procedure from January 2007 to December 2011 at our institution. Results: Twenty-five patients had valve-sparing aortic root replacement (VSR, including reimplantation or remodeling) (23 males and 2 females), and 45 patients had the Bentall procedure (34 males and 11 females). Patients who underwent a VSR were younger with a mean age of 55.4 ± 14.8 years compared to those who underwent the Bentall procedure with a mean age of 60.6 ± 12.7 (P=ns). The preoperative aortic insufficiency (AI) in the VSR group was moderate in 8 (32%) patients, and severe in 6 (24%). Preoperative creatinine was 1 ± 0.35 mg/dl in the VSR group and 1.1 ± 0.87 mg/dl in the Bentall group. In the VSR group, 3 (12%) patients had emergency surgery; by contrast, in

the Bentall group, 8 (17%) patients had emergent surgery. Concomitant coronary artery bypass grafting (excluding coronary reimplantation) was performed in 8 (32%) patients in the VSR group and in 12 (26.6%) patients in the Bentall group (P=0.78); additional valve procedures were performed in 2 (8%) patients in the VSR group and in 11 (24.4%) patients in the Bentall group. The perioperative mortality was 8% (n=2) and 13.3% (n=6), for the VSR and Bentall procedures, respectively (P=0.7, ns). The total duration of intensive care unit stay was 116.6 ± 106 hours for VSR patients and 152.5 ± 218.2 hours for Bentall patients (P=0.5). The overall length of stay in the hospital was 10 ± 8.1 days for VSR and 11 ± 9.52 days for Bentall (P=0.89). The one-year survival was 92% for the VSR group and 79.0% for the Bentall group. The seven-year survival for the VSR group was 92% and 79% for the Bentall group (95% CI [1.215 to 0.1275], P=0.1). Conclusion: Aortic valve-sparing root replacement can be performed with acceptable morbidity and mortality with a comparable long-term survival to the Bentall procedure.

Albert Einstein College of Medicine of Yeshiva University, New York, NY, United States. 2 University of Bonn, Bonn, Germany.

Correspondence adrress: Siyamek Neragi-Miandoab Montefiore Medical Center, Albert Einstein College of Medicine, Department of Cardiovascular and Thoracic Surgery 3400 Bainbridge Ave, MAP 5 – New York, NY, United States – Zip code: 10467 E-mail: siyamekneragi@yahoo.com Article received on July14th, 2013 Article accepted on September 16th, 2013

Descriptors: Aorta. Aortic aneurysm, thoracic. Aortic valve. Aortic diseases. Organ sparing treatments.

1

Work carried out Montefiore Medical Center Department of Cardiovascular and Thoracic Surgery, Albert Einstein College of Medicine of Yeshiva University, New York, NY, United States. No financial support.

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Skripochnik E, et al. - Repair of aortic root in patients with aneurysm or dissection: comparing the outcomes of valve-sparing root replacement with those from the Bentall procedure

Bentall, idade média de 60,6 ± 12,7 anos (P = ns). A insuficiência aórtica pré-operatória no grupo VSR foi moderada em oito (32%) pacientes e grave em seis (24%). Creatinina pré-operatória foi 1 ± 0,35 mg/dl, no grupo do VSR, e 1,1 ± 0,87 mg/dl, no grupo de Bentall. No grupo VSR, três (12%) pacientes foram operados em caráter de emergência e, no grupo de Bentall, oito (17%). Revascularização do miocárdio concomitante (excluindo reimplante coronariano) foi realizada em oito (32%) pacientes no grupo VSR e, em 12 (26,6%), no grupo de Bentall (P=0,78); procedimentos valvares adicionais foram realizados em 2 (8%) pacientes no grupo do VSR e em 11 (24,4%) no grupo de Bentall. A mortalidade perioperatória foi de 8% (n = 2) e 13,3% (n = 6), para os procedimentos de VSR e Bentall, respectivamente (P=0,7, ns). O tempo de internação na unidade de terapia intensiva foi de 116,6 ± 106,0 horas para pacientes VSR e 152,5 ± 218,2 horas para pacientes Bentall (P=0,5). O tempo de permanência no hospital foi de 10 ± 8,1 dias para VSR e 11 ± 9,52 dias para Bentall (P=0,89). A sobrevida em um ano foi de 92,0 % para o grupo VSR e 79,0% para o grupo de Bentall. A sobrevivência de sete anos para o grupo VSR foi de 92% e 79% para o grupo de Bentall (IC95% [1,215 a 0,1275], P=0,1). Conclusão: A técnica valve-sparing substituição da raiz aórtica pode ser realizada com a morbidade e mortalidade aceitáveis, e sobrevivência aceitável a longo prazo comparável com o procedimento de Bentall.

Abbreviations, acronyms & symbols AI AV AVR INR MI RBC STJ VSR

Aortic insufficiency Aortic valve Aortic valve replacement International normalized ratio Myocardial infarction Red blood cells Sinutubular junction Valve-sparing root replacement

Resumo Introdução: Manejo de aneurisma da aorta ou dissecção da raiz tem sido objeto de muita discussão que levou a algumas modificações. A tendência atual é o uso da técnica de substituição valve-sparing (VSR). Nós comparamos o resultado da reparação da raiz utilizando a técnica de substituição valve-sparing com o procedimento de Bentall. Métodos: Foram avaliados, retrospectivamente, 70 pacientes submetidos à substituição da raiz de aneurisma ou dissecção, comparando os resultados da técnica de substituição valve-sparing com os do procedimento Bentall de janeiro de 2007 a dezembro de 2011 em nossa instituição. Resultados: Vinte e cinco pacientes foram submetidos à substituição da valva aórtica com o uso da técnica valve-sparing (VSR, incluindo o reimplante ou remodelação) (23 homens e duas mulheres), e 45 pacientes pelo procedimento de Bentall (34 homens e 11 mulheres). Pacientes que se submeteram à VSR eram mais jovens, com idade média de 55,4 ± 14,8 anos em comparação àqueles que foram submetidos ao procedimento

Descritores: Aorta. Aneurisma da aorta torácica. Valva aórtica. Doenças da aorta. Tratamentos com preservação do órgão.

METHODS

INTRODUCTION

We retrospectively analyzed data on 70 patients with aortic root pathology (aneurysm or dissection), who underwent aortic root replacement with either the valve-sparing technique (VSR) or the Bentall procedure between 2007 and 2011 at our institution. All operations were performed using a standard approach with a median sternotomy and extracorporeal circulation. A right axillary artery or innominate artery cannulation was performed in selected cases. The patients who underwent the Bentall procedure, who received a mechanical valve, were postoperatively started on anticoagulation using warfarin, and an international normalized ratio (INR) ranging from 2.5 to 3.0 was maintained.

Management of aortic root aneurysm or dissection has been evolving in recent decades. The current trend is a valvesparing aortic root (VSR) replacement as well as restoring the diameter of the aortic annulus and sinotubular junction (STJ) [1-3]. Preservation of the native aortic valve (AV) results in maintenance of proper hemodynamics and prevention of thromboembolic complications by avoiding the use of a prosthetic valve and anticoagulation [1,4-6]. Preserving the native valve is particularly important in younger patients who refuse a mechanical valve. The crucial factors when attempting to preserve the function of the AV include adequate size and morphology of the leaflets, diameter of the STJ, and the diameter of the aortic annulus [2]. If the AV leaflets are grossly normal and aortic insufficiency (AI) is secondary to dilation of the STJ or aortic root, the native valve can be spared [6-9]. The purpose of this study was to evaluate the overall survival and compare the short- and mid-term outcomes in patients who underwent VSR with patients who underwent the Bentall procedure.

Statistical Analysis Patients’ demographics, risk factors, and postoperative outcomes were reviewed retrospectively. Perioperative mortality was defined as death for any reason occurring within 30 days after the operation or any time during the same hospitalization, regardless of the length. Survival curves were generated using Kaplan-Meier methods. For continuous

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variables, correlations were calculated with the Student t-test. Data analysis was performed with the Grafpad Prism program (GraphPad Software Inc., La Jolla, USA). This study was approved by the institutional review board at our institution.

myocardial infarction (MI) whereas none in the VSR group had previously experienced MI (P=0.044). There was no significant difference in mild or severe preoperative AI between the two groups; however, more patients in the SVR group (32%, n=8) had moderate AI, compared to those in the Bentall group (8.8%, n=4), (P=0.02). In the VSR group, three patients had undergone emergency surgery, and the remaining patients had had an elective procedure. The total perfusion time was shorter in the VSR group (222.7 ± 81.1 min) compared to the Bentall group (246.9 ± 89.8 min), P=0.27. The intraoperative need for blood transfusion was less in the VSR group compared to the Bentall group (3 units vs. 20 units, P=0.0074), which may be due to higher preoperative hematocrit in VSR patients in our series (41.8 ± 3.99 vs. 31.6 ± 4.33, P=0.0018). Concurrent CABG was performed in 8 (32%) patients in the VSR group and in 12 (26.6%) in the Bentall group (P=0.78). There was no significant difference in perioperative mortality between the two groups; 8% (n=2) and 13.3% (n=6), for VSR and Bentall groups, respectively (P=0.7, ns). Table 2 demonstrates the intraoperative parameters and differences between the two groups.

RESULTS We evaluated 70 patients who had undergone a dissection or aneurysm of the aortic root: 25 patients had VSR (23 males and two females) and 45 patients (34 males and 11 females) had the Bentall procedure. Patients with VSR were younger with a mean age of 55.4 ± 14.8 years compared to the Bentall patients who had a mean age of 60.6 ± 12.7 years (P=ns). Overall, 57 patients had an aneurysm and 13 patients had dissection of the aortic root. In patients who had replacement of the aortic root and valve, 30 patients had the traditional Bentall procedure with a mechanical aortic valve prosthesis, 10 patients had the BioBentall (replacement of the aortic valve with a bioprosthesis) procedure, and five patients had a homograft. Table 1 illustrates the patients’ characteristics, which were similar in both groups; however, seven patients in the Bentall group had previous

Table 1. Preoperative characteristics of both groups. Pre-operative parameter Age (years) Sex -Male -Female BMI (kg/m2) BSA (m2) Hypertension Hypercholesterolemia Diabetes Current smoking Coronary artery disease Cerebrovascular disease Peripheral-vascular disease COPD/ Asthma Renal failure requiring dialysis Any angina pectoris Any myocardial infarction Cardiogenic shock Any arrythmia Stroke Dissection Aortic regurgitation - Mild - Moderate - Severe Bicuspid aortic valve Hematocrit (%) White blood cells (x 103/ µL) Platelets (x 103/ µL)

Valve sparing aortic root repair (n = 25) 55.4 ± 14.8

Aortic valve replacement (n = 45) 60.6 ± 12.7

P-value

23 2 29.2 ± 6.00 2.07 ± 0.24 19 5 4 0 2 3 5 3 0 1 0 0 3 3 6

34 11 29.6 ± 7.43 1.98 ± 0.23 38 4 11 4 2 8 4 7 2 2 7 2 11 5 7

0.12 0.12 0.82 0.13 0.52 0.27 0.55 0.29 0.61 0.74 0.27 1.00 0.53 1.00 0.0449* 0.53 0.35 1.00 0.52

3 8 (32%) 6 0 41.8 ± 3.99 9.6 ± 2.2 204.1 ± 60.6

3 4 (8.8%) 11 3 31.6 ± 4.33 11.0 ± 2.89 214 ± 87.6

0.66 0.0209* 1.00 0.55 0.0018** 0.36 0.64

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Table 2. Comparing operative parameters Intraoperative parameters

Valve sparing aortic root repair, (n = 25) Any previous cardiac surgery 2 - Re-OP Sternotomy 2 -Re-OP Aortic Root/ Aorta ascendens 1 Concomitant CABG 8 Mitral/ tricuspid valve repair/ replacement 2 Cross-clamp time (min) 185.0 ± 63.3 Perfusion time (min) 222.7 ± 81.1 Longest ischemic interval (min) 28.1 ± 9.87 Total cardioplegic solution (mL) 5042.3 ± 2445.2 Cardioversion 13 Highest lactate (mmol/ L) 2.94 ± 1.49 Hematocrit after cardiopulmonary bypass (%) 28.4 ± 4.11 Red blood cell units (total) 3 Platelet units 6 Fresh frozen plasma units 5 Cryoprecipitate units 5

Bentall Procedure, (n = 45) 15 9 6 12 11 170.3 ± 63.0 246.9 ± 89.8 25.4 ± 4.28 4646.0 ± 3083.1 27 3.54 ±2.59 26.5 ± 3.64 20 21 15 8

P-value 0.07 0.31 0.41 0.78 0.12 0.37 0.27 0.15 0.61 0.62 0.34 0.67 0.0074** 0.08 0.28 1.00

Table 3. Postoperative outcome and complications. Post-operative complications

Valve sparing aortic root repair, (n = 25) Red blood cell units 17 Platelet units 10 Fresh frozen plasma units 6 Cryoprecipitate units 1 Any complications 11 (44%) Atriventricular block 1 (4%) Atrial fibrillation 6 (24%) Multisystem failure 2 (8%) Bleeding requiring reoperation 2 (8%) Infection 1 (4%) -Septicemia 1 (4%) -Sternal Infection 3 (12%) Neurological event 1 (4%) Renal failure requiring dialysis 1 (4%) Prolonged post-operative ventilation 9 (36%) Total duration of post-operative ventilation (h) 51.7 ± 84.2 Readmission to ICU 3 (12%) Total duration of ICU stay (h) 116.6 ± 106.0 Length of stay surgery – discharge (d) 10.0 ± 8.10 Readmission (< 30 days) 3 (12%) Perioperative mortality 2 (8%)

Further, the incidence of postoperative adverse events remained similar between both groups (Table 3). Postoperatively, 17 and 26 patients in the VSR and Bentall groups, respectively, required red blood cell (RBC) transfusion (P=ns). Total duration of post-operative ventilation was 51.7 ± 84.2 hours for the VSR group and 56.2 ± 121.9 for the Bentall group (P=0.89). The overall length of stay in the critical care unit was slightly longer for the Bentall group (152.5 ± 218.2

Bentall procedure, (n = 45) 28 13 11 2 24 (53.3%) 0 (0%) 11 (24.4%) 1 (2.2%) 1 (2.2%) 0 (0%) 0 (0%) 0 (0%) 1 (2.2%) 1 (2.2%) 9 (20%) 56.2 ± 121.9 4 (8.8%) 152.5 ± 218.2 11.0 ± 9.52 7 (15.5%) 6 (13.3%)

P-value 0.80 0.43 1.00 1.00 0.62 0.36 1.00 0.29 0.29 0.36 0.36 0.0420* 1.00 1.00 0.16 0.89 0.69 0.50 0.89 1.00 0.70

hours) compared to for the VSR group (116.6 ± 106.0 hours) (P=0.5). The overall length of stay was 10 ± 8.10 days for the VSR group and 11 ± 9.52 days for the Bentall group (P=0.89). The prolonged length of stay for Bentall patients may be related to anticoagulation and required time to adjust the INR prior to discharge from the hospital. The one-year survival was 92% for the VSR group and 78% for the Bentall group; the estimated survival at seven years was 92% for the VSR group

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and 78% for the Bentall group (95% CI [0.1275 to 1.215], P=0.1). The type of procedure did not impact readmission rate to the hospital. Postoperative echocardiogram was performed in 18 VSR patients (18/25; 64.3%), of which only one patient (1/18; 5.5%) had mild to moderate AI, 7 patients (7/18; 38.9%) had mild AI, and the remaining 10 patients (10/18; 55.5%) had trace AI at a median follow-up of 20 months. The freedom from aortic valve replacement following VSR at a median follow-up of 20 months was 100% (Figure 1).

underwent the Bentall procedure, and 85 patients had VSR (the David reimplantation procedure was performed in 44 patients). This observation was supported by Sheick-Yousif et al. [17], who reported a favorable outcome of valve reimplantation in 209 Marfan patients with AI secondary to dilatation of the aortic root or the STJ. Kerendi et al. [18] reported their experience with root replacement in 110 patients: 73 Bentall procedures and 37 David procedures. There was a slight, but non-significant increase in mortality with the Bentall procedure (8.2%) compared with the David procedure (5.4%), which is in concert with our results. We did not observe any significant differences with respect to postoperative stroke, renal failure, or respiratory failure between the two approaches, which has been confirmed by other authors [1,10-12,18]. Freedom from aortic valve replacement (AVR) at a mean follow-up of 8.8 months in Kerendi et al. [18] series was 94.3%. The authors argued that a VSR replacement can be performed safely in the setting of acute dissection, severe AI, and reoperations with acceptable early results. The freedom from AVR following VSR was 100% in our series; however, our results are limited by a short median follow up of 20 months. Our data demonstrated that VSR is not associated with increased postoperative morbidities; in fact, intubation time, length of stay in the critical care unit, and overall length of stay were favorable following VSR compared to those in the Bentall group. The most common complications are bleeding and neurological sequelae [15]. In a series of 388 patients (reimplantation 72, remodeling 77, tailoring 239), stroke occurred in 4.6% (18/388) [1]. In a large series of 430 patients [19] who underwent VSR (remodeling in 401, reimplantation in 29) the early mortality was 2.8%, and actuarial survival at 10 years was 83.5%. Ten-year freedom from AI grade II or greater was 85%. Operative technique (remodeling vs. reimplantation) was not associated with an increased risk of late AV regurgitation or need for AV replacement. Longterm outcome of VSR was not influenced by the technique of root repair but by the preoperative aortic root geometry and postoperative cusp configuration [19].

DISCUSSION The Bentall approach has traditionally been the gold standard for aortic root pathology; however, this approach has been challenged by the valve-sparing root replacement [1, 10-13]. The VSR can be performed without increased mortality and morbidity compared to the Bentall procedure [1,11,14,15]. The perioperative mortality in our series was 8.0% (n=2) and 13.3% (n=6) for the VSR and Bentall procedures, respectively (P=0.7, ns), which is in line with the published literature [1,11,13-15]. The better survival in the VSR group in our series may be a reflection of younger age in these patients (55.4 Âą 14.8 years compared to 60.6 Âą 12.7 years in the Bentall group); however, the difference in survival was not statistically significant. The perioperative mortality was higher in patients presenting with cardiogenic shock [15,16], long cardiopulmonary bypass and cross clamp times, concomitant CABG, and red blood cell transfusion [15]. In the Bentall group, 8 patients had undergone emergent surgery and the remaining patients had had elective surgery. Considering the small number of patients, we did not find emergency surgery to be a risk factor for operative mortality. The one-year survival in our series was 92% for the VSR group and 79% for the Bentall group; the sevenyear survival was 92% for the VSR group and 79% for the Bentall group. Although survival was favorable following VSR, this difference was not statistically significant. Cameron et al. [11] reported favorable survival following aortic valve reimplantation in a series of 372 Marfan patients; 269 patients

Fig. 1A - The overall survival. 1B. Kaplan Meier curve, comparing the survival between two groups (95% CI, 1,225 to 0,1265, P=0,10)

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Some authors reported that a preoperative aortoventricular junctional diameter greater than 28 mm was predictive of valve repair failure [19,20]. Although we did not evaluate the AV junction diameter, in our small series with a short median follow up (20 months), the AV function in the VSR group was excellent and none of the patients had significant AI. In David et al. [10] series 228 patients underwent reimplantation of the aortic valve, and 61 patients underwent remodeling of the aortic root, with excellent results. The 12-year survival was 82.9% with no difference between both techniques. The incidence of AI requiring reoperations was higher following remodeling of the aortic root. Freedom from reoperation at 12 years was 90.4% after remodeling, and 97.4% after reimplantation (not statistically significant). Freedom from moderate or severe aortic insufficiency at 12 years was 91.0% after reimplantation [10]. Dias et al. [3] reported favorable outcome with an actuarial survival and freedom from reoperation of 94.4% and 96% within 11 years of follow-up, respectively [3]. In a series of 388 patients (72 reimplantation, 77 remodeling, and 239 tailoring), the hospital survival rate was 97.4% (378/388) [1].

3. Dias RR, Mejia OV, Carvalho Jr EV, Lage DO, Dias AR, Pomerantzeff PM, et al. Análise crítica da reconstrução da raiz da aorta com a preservação da valva aórtica: 11 anos de seguimento. Rev Bras Cir Cardiovasc. 2010;25(1):66-72. 4. Ono M, Goerler H, Kallenbach K, Boethig D, Westhoff-Bleck M, Breymann T. Aortic valve-sparing reimplantation for dilatation of the ascending aorta and aortic regurgitation late after repair of congenital heart disease. J Thorac Cardiovasc Surg. 2007;133(4):876-9. 5. David TE, Feindel CM, Webb GD, Colman JM, Armstrong S, Maganti M. Aortic valve preservation in patients with aortic root aneurysm: results of the reimplantation technique. Ann Thorac Surg. 2007;83(2):S732-5. 6. David TE, Armstrong S, Ivanov J, Webb GD. Aortic valve sparing operations: an update. Ann Thorac Surg. 1999;67(6):1840-2. 7. David TE, Feindel CM, Bos J. Repair of the aortic valve in patients with aortic insufficiency and aortic root aneurysm. J Thorac Cardiovasc Surg. 1995;109(2):345-51. 8. Yacoub MH, Gehle P, Chandrasekaran V, Birks EJ, Child A, Radley-Smith R. Late results of a valve-preserving operation in patients with aneurysms of the ascending aorta and root. J Thorac Cardiovasc Surg. 1998;115(5):1080-90.

CONCLUSION Aortic VSR can be performed with acceptable morbidity and mortality. The mid-term follow up demonstrates adequate freedom from aortic insufficiency. Log-term follow up in larger series may demonstrate possibly superior long-term survival following valve sparing root repair compared to the Bentall procedure. In addition, a valve-sparing approach reduces all of the risks inherent to a mechanical or biologic prosthetic, particularly in younger patients.

9. Morimoto N, Matsumori M, Tanaka A, Munakata H, Okada K, Okita Y. Adjustment of sinotubular junction for aortic insufficiency secondary to ascending aortic aneurysm. Ann Thorac Surg. 2009;88(4):1238-43. 10. David TE, Maganti M, Armstrong S. Aortic root aneurysm: principles of repair and long-term follow-up. J Thorac Cardiovasc Surg. 2010;140(6 Suppl):S14-9. 11. Cameron DE, Alejo DE, Patel ND, Nwakanma LU, Weiss ES, Vricella LA, et al. Aortic root replacement in 372 Marfan patients: evolution of operative repair over 30 years. Ann Thorac Surg. 2009;87(5):1344-9.

Authors' roles & responsibilities ES REM VH SNM

Collecting data, manuscript writing Manuscript writing Statistical analysis Design of the project, manuscript writing

12. Ro SK, Kim JB, Hwang SK, Jung SH, Choo SJ, Chung CH, et al. Aortic root conservative repair of acute type A aortic dissection involving the aortic root: Fate of the aortic root and aortic valve function. J Thorac Cardiovasc Surg. 2013;146(5):1113-8. 13. Silva VF, Real DS, Branco JN, Catani R, Kim HC, Buffolo E, et al. Bentall and De Bono surgery for correction of valve and ascending aortic disease: long-term results. Rev Bras Cir Cardiovasc. 2008;23(2):256-61.

REFERENCES 1. Svensson LG, Deglurkar I, Ung J, Pettersson G, Gillinov AM, D’Agostino RS, et al. Aortic valve repair and root preservation by remodeling, reimplantation, and tailoring: technical aspects and early outcome. J Card Surg. 2007;22(6):473-9.

14. Montalvo J, Razzouk A, Wang N, Bansal R, Rasi A, Hasaniya N, et al. Aortic root surgery does not increase the operative risk of acute type A aortic dissection. Am Surg. 2011;77(1):88-92.

2. Neragi-Miandoab S. Repair of dilated aortic root and sinotubular junction using a stabilizer ring. Recent Pat Cardiovasc Drug Discov. 2012;7(2):134-40.

15. Ghavidel AA, Tabatabaei MB, Yousefnia MA, Omrani GR,

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Givtaj N, Raesi K. Mortality and morbidity after aortic root replacement: 10-year experience. Asian Cardiovasc Thorac Ann. 2006;14(6):462-6.

18. Kerendi F, Guyton RA, Vega JD, Kilgo PD, Chen EP.. Early results of valve-sparing aortic root replacement in high-risk clinical scenarios. Ann Thorac Surg. 2010;89(2):471-6.

16. Schwartz JP, Bakhos M, Patel A, Botkin S, Neragi-Miandoab S. Repair of aortic arch and the impact of cross-clamping time, New York Heart Association stage, circulatory arrest time, and age on operative outcome. Interact Cardiovasc Thorac Surg. 2008;7(3):425-9.

19. Kunihara T, Aicher D, Rodionycheva S, Groesdonk HV, Langer F, Sata F, et al. Preoperative aortic root geometry and postoperative cusp configuration primarily determine long-term outcome after valve-preserving aortic root repair. J Thorac Cardiovasc Surg. 2012;143(6):1389-95.

17. Sheick-Yousif B, Sheinfield A, Tager S, Ghosh P, Priesman S, Smolinsky AK, et al. Aortic root surgery in Marfan syndrome. Isr Med Assoc J. 2008;10(3):189-93.

20. Sch채fers HJ, Kunihara T, Fries P, Brittner B, Aicher D. Valvepreserving root replacement in bicuspid aortic valves. J Thorac Cardiovasc Surg. 2010;140(6 Suppl):S36-40.

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Barbieri LR, et al. - Incidence of stroke and acute renal failure in ORIGINAL ARTICLE patients of postoperative atrial fibrillation after myocardial revascularization

Incidence of stroke and acute renal failure in patients of postoperative atrial fibrillation after myocardial revascularization

Incidência de acidente vascular encefálico e insuficiência renal aguda em pacientes com fibrilação atrial no pós-operatório de cirurgia de revascularização do miocárdio

Lucas Regatieri Barbieri1, MD; Marcelo Luiz Peixoto Sobral1,2, MD; Glaucio Mauren da Silva Gerônimo1, MD; Gilmar Geraldo dos Santos1,2,3, MD, PhD; Evandro Sbaraíni1, MD; Fabio Kirzner Dorfman1, MD; Noedir Antônio Groppo Stolf1,4, MD, PhD

DOI: 10.5935/1678-9741.20130073

RBCCV 44205-1495

Abstract Introduction: Postoperative atrial fibrillation is the most common arrhythmia in cardiac surgery, its incidence range between 20% and 40%. Objective: Quantify the occurrence of stroke and acute renal insufficiency after myocardial revascularization surgery in patients who had atrial fibrillation postoperatively. Methods: Cohort longitudinal bidirectional study, performed at Portuguese Beneficent Hospital (SP), with medical chart survey of patients undergoing myocardial revascularization surgery between June 2009 to July 2010. From a total of 3010 patients were weaned 382 patients that presented atrial fibrillation preoperatively and/or associated surgeries. The study was conducted in accordance with national and international following resolutions: ICH Harmonized Tripartite Guidelines for Good Clinical Practice - 1996; CNS196/96 Resolution, and Declaration of Helsinki. Results: The 2628 patients included in this study were divided into two groups: Group I, who didn’t show postopera-

tive atrial fibrillation, with 2302 (87.6%) patients; and group II, with 326 (12.4%) who developed postoperative atrial fibrillation. The incidence of stroke in patients was 1.1% without postoperative atrial fibrillation vs. 4% with postoperative atrial fibrillation (P<0.001). Postoperative acute renal failure was observed in 12% of patients with postoperative atrial fibrillation and 2.4% in the group without postoperative atrial fibrillation (P<0.001), that is a relation 5 times greater. Conclusion: In this study there was a high incidence of stroke and acute renal failure in patients with postoperative atrial fibrillation, with rates higher than those reported in the literature.

Hospital Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, São Paulo, SP, Brazil. 2 Brazilian Medical Association (AMB), São Paulo, SP, Brazil. 3 Heart Institute at the Faculty of Medicine of the University of São Paulo (InCor-FMUSP), São Paulo, SP, Brazil. 4 Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo, SP, Brazil.

Correspondence address: Lucas Regatieri Barbieri Real e Benemérita Associação Portuguesa de Beneficência de São Paulo R Maestro Cardim, 769 – Bela Vista- São Paulo, SP Brazil – Zip code: 01323-001 E-mail: lrbarbieri@msn.com

Descriptors: Cardiovascular diseases. Atrial fibrillation. Myocardial revascularization. Stroke. Renal insufficiency. Resumo Introdução: A fibrilação atrial pós-operatória é a arritmia mais comum em cirurgia cardíaca; estima-se sua incidência entre 20% e 40%.

1

This study was carried out at Hospital Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, São Paulo, SP, Brazil. There was no financial support.

Article received on May 16th, 2013 Article accepted on September 2nd,2013

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apresentavam fibrilação atrial no pré-operatório e/ou cirurgias associadas). O estudo foi conduzido em conformidade com as seguintes resoluções nacionais e internacionais: ICH Harmonized Tripartite Guidelines for Good Clinical Practice - 1996; Resolução CNS196/96; e Declaração de Helsinque. Resultados: Os 2628 pacientes incluídos neste estudo foram divididos em dois grupos: grupo I, que não apresentou fibrilação atrial no pós-operatório, com 2302 (87,6%) pacientes; e grupo II, com 326 (12,4%) que evoluíram com fibrilação atrial no pós-operatório. A incidência de acidente vascular encefálico nos pacientes foi de 1,1% sem fibrilação atrial no pós-operatório vs. 4% com fibrilação atrial no pós-operatório (P<0,001). Insuficiência renal aguda pós-operatória ocorreu em 12% dos pacientes com fibrilação atrial no pós-operatório e 2,4% no grupo sem fibrilação atrial no pós-operatório (P<0,001), ou seja, uma relação 5 vezes maior. Conclusão: Neste estudo verificou-se alta incidência de acidente vascular encefálico e insuficiência renal aguda nos pacientes com fibrilação atrial no pós-operatório, sendo as taxas maiores que as referidas na literatura.

Abbreviations, acronyms & symbols CVA CPB CVD COPD APE AF POAF CHF ARF SPSS ICU

Cerebrovascular accident Cardiopulmonary Bypass Cardiovascular Diseases Chronic obstructive pulmonary disease Acute Pulmonary Edema Atrial fibrillation Postoperative atrial fibrillation Congestive heart failure Acute renal failure Statistical Package for Social Sciences Intensive care unit

Objetivo: Avaliar a incidência de acidente vascular encefálico e insuficiência renal aguda nos pacientes que apresentaram fibrilação atrial no pós-operatório de cirurgia de revascularização miocárdica. Métodos: Estudo coorte longitudinal, bidirecional, realizado no Hospital da Beneficência Portuguesa (SP), com levantamento de prontuários de pacientes submetidos à cirurgia de revascularização miocárdica, de junho de 2009 a julho de 2010. De um total de 3010 pacientes foram retirados 382 pacientes, que

Descritores: Doenças cardiovasculares. Fibrilação atrial. Revascularização miocárdica. Acidente vascular cerebral. Insuficiência renal.

INTRODUCTION

ing cause of post-discharge cardiac [9] surgery hospital readmission. Cerebrovascular accident (CVA), acute renal failure (ARF), hypotension, acute pulmonary edema (APE), increased length of stay in the intensive care unit (ICU) and estimated $ 10,000 in additional costs are directly associated with complications POAF [7,10]. Its occurrence is also associated with increased twice cardiovascular morbidity and mortality (4.7% versus 2.1% in the short term) [6-11]. The wide variation in the incidence of stroke and ARF in the postoperative period between studies, has a multifactorial profile including different diagnostic criteria, study design, inclusion and exclusion criteria, patient profiles and the centers involved in the sample making it difficult the comparison between studies. The incidence of ARF in cardiac surgery ranges from 3.5 % to 31.0 % [12-14], and the need for dialysis was present in 0.3% to 15.0% of cases. The presence of acute renal failure in these patients increases the mortality rate of 0.4% to 4.4% to 1.3% to 22.3% and when there is need for dialysis such rates reach 25.0% at 88.9% [12-14], making it an independent risk factor for mortality. This study aims to assess the incidence of stroke and acute renal failure in patients with POAF of coronary artery bypass grafting.

Life expectancy has increased in Western countries. According to the last census of the IBGE (2011), the elderly population in Brazil is also increasing across the country. This aging population have produced a greater number of hospitalizations, particularly those related to the presence of cardiovascular disease (CVD) [1,2]. Atrial fibrillation in the Postoperative (POAF) of cardiac surgery is the most common arrhythmia [3], it is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of atrial function [4]. Its incidence is estimated at 20% to 40% and are believed to occur most frequently between the second and the fifth day after surgery [4-7]. Physiopathologically, it involves multiple factors such as pre-existing heart degenerative changes, dispersion of atrial refractoriness, changes in the speed of atrial conduction and atrial transmembrane potential so as to prolong hypokalemia Phase 3 depolarization, increasing automative and decreasing the conduction speed, oxidative stress, inflammation, atrial fibrosis, excessive production of catecholamines, changes in autonomic tone and expression of connexins. These changes result in increased dispersion of atrial refractoriness as well as the formation of a pro-arrhythmic substrate [8]. The length of stay of patients who develop POAF increases, on average, two to four days compared to those who remained in sinus rhythm, and this disease is the lead-

METHODS Longitudinal cohort bidirectional study. The sample consisted of 3010 subjects greater than 18 years who underwent

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coronary artery bypass grafting at Hospital da Beneficência Portuguesa de São Paulo in June 2009 to July 2010 period. Inclusion criteria were patients aged ≥ 18 years who underwent coronary artery bypass grafting without other associated procedures. Exclusion criteria were: submission of the patient to any type of concomitant cardiac or non-cardiac surgery; patients with chronic atrial fibrillation and/or congenital cardiac surgery. From a total of 3010 patients, 382 patients were excluded: 60 (1.99%) patients with preoperative arrhythmia (chronic or paroxysmal atrial fibrillation, atrial flutter), and 322 (10.7%) patients because they had associated procedures to CABG (Table 1). ARF was defined as creatinine level at or above 2.2 mg/ dl and the clearance creatinine lower than 60ml plasma/ min/1,73m2. For statistical analysis, we used the statistical package SPSS (Statistical Package for Social Sciences) for Windows, version 16.0, and R: A Language and Environment for Statistical Computing. All tests were performed with consideration of bilateral

hypotheses, we assumed a significance level of α=5%. Initially we used descriptive statistics to assess the absolute and relative frequency, mean, standard deviation, median and interquartile range of the variables, with graphical presentation. When checking the equality of proportions between groups on the variables studied, the chi-square test or Fisher’s exact test were used, depending on the variable analyzed be qualitative or quantitative. Comparison between quantitative variables was performed using the Student t test or nonparametric Mann-Whitney test (when comparing two groups) or ANOVA or the nonparametric Kruskal-Wallis test (when comparing three or more groups) [15]. The project was submitted, reviewed and approved by the Research Ethics Committee of RBAPB, under protocol number 760-11 accepted on November 4, 2011. It was performed in accordance with the following national and international resolutions: ICH Harmonized Tripartite Guidelines for Good Clinical Practice - 1996; CNS196/96 Resolution, and the Declaration of Helsinki.

Table 1. Descriptive values of demographic variables, procedure and preoperative risk factors, according to the AF group. Variable Age Male Race BMI Smoke CAD DM Dyslipidemia ARF SAH SAP DAP Previous stroke COPD Peripheral arterial failure Cerebrovascular disease Creatinine >2,2mg/dl Creatinine Clearance < 60

Category White Black Brownish Asian Ex No Yes

diabetes mellitus

Without (n=2302) 61.2 ± 9,3 1597 69.4% 1938 84.2% 94 4.1% 242 10.5% 28 1.2% 27.1 ± 4.1 910 39.5% 1017 44.2% 375 16.3% 698 30.3% 853 37.1% 1023 44.4% 108 4.7% 1898 82.5% 132.8 ± 20.1 80.6 ± 11.8 120 5.2% 142 6.2% 97 4.2% 39 1.7% 48 2.1% 995 43.6%

AF

With (n=326) 66.8 ± 8.9 239 73.3% 283 86.8% 13 4.0% 26 8.0% 4 1.2% 27.0 ± 3.9 135 41.4% 155 47.6% 36 11.0% 97 29.8% 117 35.9% 143 43.9% 29 8.9% 272 83.4% 134.9 ± 21.0 80.8 ± 12.2 15 4.6% 36 11.0% 24 7.4% 7 2.2% 16 4.9% 188 57.7%

P < 0.001(1) 0.147(3) 0.564(3) 0.697(1) 0.050(2) 0.835(2) 0.683(2) 0.845(2) 0.001(2) 0.661(2) 0.105(1) 0.869(1) 0.640(2) 0.001(2) 0.011(2) 0.559(3) 0.002(2) < 0.001(2)

( 1 ) descriptive level of probability of Student's t test. ( 2 ) descriptive level of probability of the chi-square test. ( 3 ) descriptive level of probability of the Fisher exact test. AF = atrial fibrilation; BMI = body mass index; CAD = coronary artery disease; DM = diabetes mellitus; ARF = acute renal failure; SAH =systemic arterial hypertension; SAP = systolic arterial pressure; DAP = diastolic arterial pressure; COPD = chronic obstructive pulmonary disease

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RESULTS

and surgical indication. Among these, the indication for urgent/emergency surgery proved to be one predisposing factor to the onset of POAF, which was 2.4% in those who underwent urgent/emergency surgery (group I: 16 to 0.7%, group II: 8 to 2.4 %, P=0.006). We found that the occurrence of cases with postoperative blood transfusion, stroke and ARF, rehospitalization at 30 days and at 1 year and death was significantly higher in patients with AF (Tables 3 and 4). In the group that evolved without the presence of AF the incidence of stroke and postoperative ARF was 1.1% and 2.4%, respectively, while this number was 4% and 12% in group II (with POAF) with P<0.001.

Patients included in this study (2,628) were divided into two groups: group I, who had no POAF, with 2,302 (87.6%) patients, and group II, with 326 (12.4%) patients who developed POAF. After assessing the predictive factors, we compared their evolution. The mean age of patients was 61.9 +9.5 years. Eighteen hundred and thirty-six (69.9%) patients were male. Table 2 shows the descriptive values of variables: indication for surgery, and of intraoperative, according to the groups with and without POAF, the intraoperative variables

Table 2. Descriptive values of variables: surgical indication and intraoperative, according to the groups with and without POAF.

Variable Surgical indication Use of IAB CPB Clamping time Degree of Hypothermia Myocardial protection

Category Elective Urg./Emerg.

28° 31° 34° Normothermia Clamping Cardioplegia

Group I Without (n=2302) 2286 99.3% 16 0.7% 5 0.2% 2000 86.9% 43.6 ± 19.5 40 2.0% 672 33.6% 640 32.0% 648 32.4% 12 0.6% 1988 99.4%

AF

P

Group II With (n=326) 318 97.6% 8 2.4% 3 0.9% 282 86.5% 45.5 ± 19.1 4 1.4% 84 29.8% 94 33.3% 100 35.5% 3 1.1% 279 98.9%

0.006(3) 0.066(3) 0.850(2) 0.075(4) 0.501(2) 0.418(3)

( 1 ) descriptive level of probability of Student's t test ( 2 ) descriptive level of probability of the chi-square test ( 3 ) descriptive level of probability of the Fisher exact test ( 4) descriptive probability level of non-parametric Mann -Whitney test IAB - Intra-aortic balloon ; CPB - Cardiopulmonary bypass

Table 3. Incidence values of Stroke and ARF in the postoperative period.

Variable Postoperative stroke Postoperative ARF

Without (n=2302) 26 1.1% 56 2.4%

AF

With (n=326) 13 4.0% 39 12.0%

1. descriptive level of probability of the Fisher exact test 2 . descriptive level of probability of the chi-square test

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P < 0.001(1) < 0.001(2)

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Barbieri LR, et al. - Incidence of stroke and acute renal failure in patients of postoperative atrial fibrillation after myocardial revascularization

Table 4. Descriptive values for the postoperative period variables. Variable Readmission within 30 days Rehospitalization at 1 year Length of postoperative hospital stay Total length of hospital stay Death up to 1 year

Without (n=2302) 168 7.6% 417 18.7% 8.1 ± 11.5 10.6 ± 12.2 109 4.7%

AF

With (n=326) 34 12.8% 73 25.9% 16.4 ± 26.1 19.3 ± 26.5 57 17.5%

P 0.004(3) 0.004(3) < 0.001(1) < 0.001(1) < 0.001(3)

1. descriptive level of probability of the non-parametric Mann-Whitney test 2 . descriptive level of probability of the Fisher exact test 3 . descriptive level of probability of the chi-square test

DISCUSSION

Another aspect worth noting is that the incidence of ARF that is also higher in the group with POAF: 12%, versus only 4% in group I, or that is, an incidence three times higher. A study assessing risk factors for the occurrence of stroke, transient ischemic attack and ARF in the postoperative period of CABG surgery found that atrial fibrillation and low cardiac output were significantly related to those complications [10,11,18,19]. The presence of conditions that determine hypoperfusion and renal ischemia is directly related to the development of ARF and patients with reduced renal functional reserve, where there is a reduction in glomerular filtration rate without elevation of serum creatinine above normal values, and are more likely to develop AKI even with minor kidney injuries. Preoperative and intraoperative factors such as age, previous level of creatinine, diabetes mellitus, cardiac output, cardiopulmonary bypass time and the use of intra-aortic balloon influence the development of ARF [12-14,16]. The development of postoperative complications such as infection, bleeding, and use of nephrotoxic substances can cause the level of severity of AKI is higher. The manipulation of the aorta appears to be an important causal factor for stroke after cardiac surgery, either secondary to large emboli as well as a result of microemboli (shower embolism). It is likely that a better preoperative study of the aorta and a careful handling may help reduce this incidence, and this includes: improved diagnosis and treatment of aortic disease with epiaortic ultrasound or transesophageal echocardiography, care in the preparation of the proximal coronary anastomoses without aortic unclamping (minimizing the aortic trauma), and the use of “screens” for protection during aortic manipulation. Moreover, a better understanding is needed with regard to the relative contribution of the CPB circuit to embolic events, especially arterial line filter. On the other hand, cerebral hypoperfusion, both intraoperative and during the immediate

When we assessed the period in which the highest incidence of AF occurs, we found an average of 2.6 days with a median on day 2, which is in agreement with the literature [4-7]. As described by Leitch et al. [ 3], it was proved that age was a predisposing factor to a higher incidence of AF, with a P < 0.001. It was also proven its inference as a predisposing factor to increased incidence of POAF, and the average age in this group was six years older, showing a univariate assessment as an isolated predisposing factor to increased incidence of POAF. While in group I the mean age of patients was around 61 years old, in group II such average was around 67 years old. Age is a risk factor widely cited and discussed in the literature [3,16,17], probably due to the higher content of collagen fibrillation in elderly patients and degeneration of the conduction system. Relevant statistic data observed in this study was the appearance of almost double the cases of POAF in patients with CRF (4.7% versus 8.9%) and creatinine ≥ 2.2 mg/dl (2.1% versus 4.9%), which indicates the close relationship of these as aggravating for the onset of POAF. The same proportion in those with chronic obstructive pulmonary disease (COPD) (6.2% versus 11%). Through study of preoperative prognostic factors we observed that age, male gender, COPD, congestive heart failure (CHF ) and creatinine ≥ 2.2 mg/dl are risk factors for the occurrence of AF. We found a significant association between POAF and higher incidence of stroke and postoperative ARF. Creswell et al. [ 11 ] reported that patients developing postoperative atrial fibrillation had a 3.3% incidence of stroke, while those who did not develop the incidence was only 1.4% (P<0.005). Our study revealed, in a statistically significant univariate analysis, a higher incidence in cases of patients who developed POAF (1.1% vs 4.0% group I group II, P<0.001).

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postoperative period should be avoided, especially in patients with prior stroke or cerebrovascular disease [18,20]. We observed that the occurrence of POAF is associated with a significantly increased length of hospital stay, according to the literature. The length of ICU stay was longer in the POAF group 16 days on average (P<0.001 ), 8 days higher when comparing the patients in group I (twice as long), confirming its impact on morbidity and mortality [10,11,17,18,21]. In the present study, the hospital mortality of patients with POAF was higher than expected mortality rate for this type of elective surgery. The readmission rate within 30 days, and readmission within 1 year had a high incidence in patients with atrial fibrillation. This observational finding is consistent with other studies which have attributed to AF increased risk for patients in both short- and long-term [9,11,19,21,22].

age as a predictor of atrial fibrillation and flutter after coronary bypass grafting. J Thorac Cardiovasc Surg. 1990;100(3):338-42. 4. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al; American College of Cardiology/ American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; European Heart Rhythm Association; Heart Rhythm Society.. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114(7):e257-e354. 5. Dunning J, Treasure T, Versteegh M, Nashef SA; EACTS Audit and Guidelines Committee. Guidelines on the prevention and management of de novo atrial fibrillation after cardiac and thoracic surgery. Eur Cardiothorac Surg. 2006;30(6):852-72.

CONCLUSION In this study there was a high incidence of stroke and acute renal failure in patients with POAF, with rates higher than those reported in the literature Once the groups are not fully comparable, a definitive conclusion would be observed after more detailed studies.

6. Banach M, Misztal M, Goch A, Rysz J, Goch JH. Predictors of atrial fibrillation in patients following isolated surgical revascularization. A meta-analysis of 9 studies with 28786 patients. Arch Med Sci. 2007;3(3):229-39. 7. Filardo G, Hamilton C, Hebeler RF Jr, Hamman B, Grayburn P. New-onset postoperative atrial fibrillation after isolated coronary artery bypass graft surgery and long-term survival. Circ Cardiovasc Qual Outcomes. 2009;2(3):164-9.

Authors' roles & responsibilities LRB MLPS GMSG GGS ES FKO NAGS

Idealizer of the study Article Review Aid in medical records survey Article Review Aid in medical records survey Aid in the statistical part of the article Article Review

8. Oliveira DC, Ferro CR, Oliveira JB, Prates GJ, Torres A, Egito ES, et al. Postoperative atrial fibrillation following coronary bypass graft: clinical factors associated with in-hospital death. Arq Bras Cardiol. 2007;89(1):16-21. 9. Lahey SJ, Campos CT, Jennings B, Pawlow P, Stokes T, Levitsky S. Hospital readmission after cardiac surgery. Does “fast-track” cardiac surgery result in cost saving or cost shifting? Circulation. 1998;98(19 Suppl):II35-40. 10. Chung MK, Asher CR, Dykstra D, Dimengo J, Weber M, Whitman G, et al. Atrial fibrillation increases length of stay and cost after cardiac surgery in low risk patients targeted for early discharge. J Am Coll Cardiol. 1996;27:9A.

REFERENCES 1. Vegni R, Almeida GF, Braga F, Freitas M, Drumond LE, Penna G, et al. Complicações após cirurgia de revascularização miocárdica em pacientes idosos. Rev Bras Ter Intensiva. 2008;20(3):226-34.

11. Creswell LL, Schuessler RB, Rosenbloom M, Cox JL. Hazards of postoperative atrial arrhythmias. Ann Thorac Surg. 1993;56(3):539-49.

2. IBGE - Instituto Brasileiro de Geografia e Estatística. Primeiros resultados definitivos do Censo 2010: população do Brasil é de 190.755.799 pessoas. Comunicação Social, 2011 [Acesso em: 02 set. 2011]. Disponível em: <http://www.ibge.gov.br/home/presidencia/noticias/noticia_ visualiza.php?id_noticia=1866&id_pagina=1>

12. Mangos GJ, Brown MA, Chan WY, Horton D, Trew P, Whitworth JA. Acute renal failure following cardiac surgery: incidence, outcomes and risk factors. Aust N Z J Med. 1995;25(4):284-9. 13. Abel RM, Buckley MJ, Austen WG, Barnett GO, Beck CH Jr, Fischer JE. Etiology, incidence, and prognosis of renal

3. Leitch JW, Thomson D, Baird DK, Harris PJ. The importance of

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failure following cardiac operations. Results of a prospective analysis of 500 consecutive patients. J Thorac Cardiovasc Surg. 1976;71(3):323-33.

18. Engelman DT, Cohn LH, Rizzo RJ. Incidence and predictors of tias and strokes following coronary artery bypass grafting: report and collective review. Heart Surg Forum. 1999;2(3):242-5.

14. Conlon PJ, Stafford-Smith M, White WD, Newman MF, King S, Winn MP, et al. Acute renal failure following cardiac surgery. Nephrol Dial Transplant. 1999;14(5):1158-62.

19. Narayan SM, Cain ME, Smith JM. Atrial fibrillation. Lancet. 1997;350(9082):943-50. 20. Mayr A, Knotzer H, Pajk W, Luckner G, Ritsch N, Dünser M, et al. Risk factors associated with new onset tachyarrhythmias after cardiac surgery: a retrospective analysis. Acta Anaesthesiol Scand. 2001;45(5):543-9.

15. Rosner B. Fundamentals of biostatistics. Boston: PWS Publishers; 1986. 584p. 16. Amar D, Zhang H, Leung DH, Roistacher N, Kadish AH. Older age is the strongest predictor of postoperative atrial fibrillation. Anesthesiology. 2002;96(2):352-6.

21. Ommen SR, Odell JA, Stanton MS. Atrial arrhythmias after cardiothoracic surgery. N Eng J Med. 1997;336(20):1429-34.

17. Aranki SF, Shaw DP, Adams DH, Rizzo RJ, Couper GS, VanderVliet M, et al. Predictors of atrial fibrillation after coronary artery surgery: Current trends and impact on hospital resources. Circulation. 1996;94(3):390-7.

22. Lima MAVB, Sobral MLP, Mendes Sobrinho C, Santos GG, Stolf NAG. Fibrilação atrial e flutter após operação de revascularização do miocárdio: fatores de risco e resultados. Rev Bras Cir Cardiovasc. 2001;16(3):244-50.

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Rossi Neto JM, et al. - Myocardial protection with prophylactic oral metoprolol ORIGINAL ARTICLE during coronary artery bypass grafting surgery: evaluation by troponin I

Myocardial protection with prophylactic oral metoprolol during coronary artery bypass grafting surgery: evaluation by troponin I Proteção cardíaca com uso profilático de betabloqueador oral em cirurgia de revascularização miocárdica: avaliação pela troponina I

João Manoel Rossi Neto1, MD, PhD; Carlos Gun1, MD, PhD; Rui Fernando Ramos1, MD, PhD; Antonio Flavio Sanchez de Almeida1, MD, PhD; Mario Issa1, MD, PhD; Vivian Lener Amato1, MD, PhD; Jarbas J. Dinkhuysen1, MD, PhD; Leopoldo Soares Piegas1, MD, PhD

DOI: 10.5935/1678-9741.20130074

RBCCV 44205-1496

Abstract Introduction: Biochemical markers of myocardial injury are frequently altered after cardiac surgery. So far there is no evidence whether oral beta-blockers may reduce myocardial injury after coronary artery bypass grafting. Objective: To determine if oral administration of prophylactic metoprolol reduces the release of cardiac troponin I in isolated coronary artery bypass grafting, not complicated by new Q waves. Methods: A prospective randomized study, including 68 patients, divided in 2 groups: Group A (n=33, control) and B (n=35, beta-blockers). In group B, metoprolol tartrate was administered 200 mg/day. The myocardial injury was assessed by troponin I with 1 hour and 12 hours after coronary artery bypass grafting. Results: No significant difference between groups regarding pre-surgical, surgical, complication in intensive care (15% versus 14%, P=0.92) and the total number of hospital events (21% versus 14%, P=0.45) was observed. The median value of troponin I with 12 hours in the study population was 3.3 ng/ml and was lower in group B than in group A (2.5 ng/ml versus 3.7 ng/ ml, P<0,05). In the multivariate analysis, the variables that have

shown to be independent predictors of troponin I release after 12 hours were: no beta-blockers administration and number of vessels treated. Conclusion: The results of this study in uncomplicated coronary artery bypass grafting, comparing the postoperative release of troponin I at 12 hours between the control group and who used oral prophylactic metoprolol for at least 72 hours, allow to conclude that there was less myocardial injury in the betablocker group, giving some degree of myocardial protection.

Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brazil.

Correspondence address: João Manoel Rossi Neto Instituto Dante Pazzanese de Cardiologia Ambulatório novo-Setor de Disfunção Ventricular Av. Dante Pazzanese, 500 – Vila Mariana – São Paulo, SP, Brazil – Zip code: 04012-180 E-mail: jmrossi@sti.com.br Article received on March 4th, 2013 Article accepted on July 10th, 2013

1

Descriptors: Troponin I. Postoperative care. Adrenergic beta-antagonists. Resumo Introdução: Os marcadores bioquímicos de lesão miocárdica estão frequentemente alterados após cirurgia cardíaca. Até o momento não existem evidências de que o betabloqueador oral possa reduzir a lesão miocárdica após cirurgia de revascularização miocárdica. Objetivo: Determinar se a administração oral profilática de metoprolol reduz a liberação de troponina cardíaca I na cirur-

Work carried out at Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brazil. No financial support.

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dência de complicações na terapia intensiva (15% versus 14%; P=0,92) e o número total de eventos hospitalares (21% versus 14%; P=0,45). O valor da mediana da troponina I com 12 horas na população estudada foi de 3,3 ng/ml e foi menor no grupo B do que no grupo A (2,5 ng/ml versus 3,7 ng/ml; P<0,05). Na análise multivariada, as variáveis que demonstraram serem preditoras independentes da liberação de troponina cardíaca I com 12 horas foram: não uso de betabloqueadores e número de vasos tratados. Conclusão: Os resultados desta investigação na cirurgia de revascularização miocárdica isolada, não complicada, comparando a liberação pós-operatória de troponina cardíaca I com 12 horas entre os grupos controle e o que usou metoprolol oral profilático por pelo menos 72 horas, permitem concluir que houve menor lesão miocárdica no grupo betabloqueador, conferindo algum grau de proteção miocárdica.

Abbreviations, acronyms & symbols CABG Coronary artery bypass grafting EKG Electrocardiogram ICU Intensive Care Unit MMN Markers of myocardial necrosis TnI Troponin I

gia de revascularização miocárdica isolada não complicada por novas ondas Q. Métodos: Estudo prospectivo, randomizado, incluindo 68 pacientes divididos em 2 grupos: Grupo A (n=33, controle) e B (n=35, betabloqueador). No grupo B, o tartarato de metoprolol foi administrado na dose de 200 mg/dia. A lesão miocárdica foi avaliada pela troponina I com 1 hora e 12 horas após a cirurgia de revascularização miocárdica. Resultados: Não foi observada diferença significativa entre os grupos quanto às variáveis pré-cirúrgicas, cirúrgicas, inci-

Descritores: Troponina I. Cuidados pós-operatórios. Antagonistas adrenérgicos beta.

INTRODUCTION

to describe the plasma levels of markers of myocardial necrosis (MMN) as troponins, released in CABG that are not caused by infarction postoperatively and evaluate possible myocardial protection procedures that could reduce the MI. It is plausible to expect that the results of the protective effects of beta-blockers can be extrapolated to CABG. Therefore, the aim of this study is to test the hypothesis that the prophylactic use of oral metoprolol tartrate reduces MI, assessed by the release of troponin I (TnI) in the first 12 hours of post-CABG alone and not complicated by the presence of new Q waves on the electrocardiogram (EKG), conferring myocardial protection.

An increase in troponin levels is observed following cardiac surgery, indicating myocardial injury [1,2]. The values considered normal or expected after coronary artery bypass grafting (CABG) suffer multifactorial influences such as type of surgery, duration of ischemia and myocardial protection, inflammatory response, reperfusion injury, excessive stretching and contraction of the heart, atheromatous embolism, inadequate coronary perfusion and excessive perioperative cardiac work. Beta-blockers can be defined as pharmacologic agents that antagonize specifically, competitive and reversible the action of endogenous or exogenous catecholamine in beta-adrenergic receptors. Particularly in the heart, beta-adrenergic stimulation leads to increased heart rate and myocardial contractility. Depending upon the selective ability to antagonize the effects of catecholamines in certain tissues at doses lower than those required in others, beta-blockers may be classified as selective and non-selective. The beta-1 selective blockers are considered cardioselective because the heart contains predominantly beta-1 and less beta-2; since the bronchodilation is mediated by beta-2 receptors, and this characteristic is dose-dependent and decreases or disappears when employing high doses. Possible deleterious effects resulting from the use of beta-blockers that could cause myocardial depression and/ or worsening of existing lung disease, however, are of concern for some cardiac surgeons. The clinical benefits of beta-blocker therapy have been proven in the treatment of myocardial infarction, heart failure, protection of preoperative patients with ischemic heart disease and in the prevention of atrial fibrillation postoperatively [3,4]. From the clinical and research perspective, it is desirable

METHODS This is a randomized, open-label and single center study. Inclusion criteria for the study were indication for CABG regardless of age or gender with signed informed consent term. Exclusion criteria for the study were: previous use of beta-blockers; contraindication to beta-blockers; clinical signs of systolic heart failure, global ejection fraction less than 50%; CABG associated with other procedures (valve replacement or aneurysmectomy or endoaneurysmorrhaphy), presence of new Q waves on EKG during the period of stay in the Intensive Care Unit (ICU) and presence of acute myocardial infarction less than 30 days of evolution. All patients underwent CABG with the same surgical technique (intermittent aortic clamping) and a graft of the left internal thoracic artery had to be implanted. The metoprolol tartrate (oral) was initiated at least 72 hours before surgery, in the target dose of 200 mg/day. TnI concentrations were determined by immunometric method using the Immulite Analyser (DPC - Diagnostic Products Corporation - Los Angeles, USA). Three samples

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of blood were collected for the determination of TnI: in the preoperative period, with one hour and 12 hour arrival in the ICU. A program developed by the authors of the EuroSCORE was used for the score calculation of each patient [5]. The intercurrences and complications (inotropes >24 hours, intubation >24 hours, temporary pacemaker, the ICU stay for >24 hours, stroke, atrial fibrillation, and death) were registered in the medical record and transferred to the clinical form of the study. Due to the difficulty of finding information on the variability of the difference between TnI between the two groups (with and without beta-blockers) initially several simulations were performed to estimate the sample size. After the completion of the study, the statistical difference (1.2) and standard deviation of the difference (1.7) were calculated, and it was observed a test power of 85%. Results were expressed as mean and standard error or median and quartiles for quantitative variables, while qualitative variables were expressed as relative frequencies. Possible associations between qualitative variables were evaluated using the chi-square or Fisher exact test. For comparison of quantitative variables between the control and beta-blocker groups was used t-test for variables with normal distribution and for those without normal distribution (with an hour I TnI, TnI 12 hours and number of vessels treated) the Mann-Whitney test was applied. The Spearman correlation was used to examine the association between quantitative variables and Tn I of 12 hours. For the choice of the independent variables on the model of multivariate analysis, variables that had significant correlation were selected and by clinical judgment the ones that could also influence the release of TnI 12 hours. For the selection of best model, which had a reduced number of variables the Akaike method was applied, that uses a generalized linear model of

gamma distribution (link function log). The gamma model was selected by presenting a better fit in the residual analysis. Results were considered statistically significant when P-values were less than 0.05. This study was approved by the Ethics Research Committee of our Institution (protocol number: 2089). RESULTS Initially 70 patients were selected and after recruitment, two cases were not considered from the analysis because they had new Q waves on EKG 12 hours after surgery. Patients were allocated for two groups, 33 (48.5%) patients in the control group, and the other 35 (51.5%) in the beta-blocker group. The dose in one patient was reduced to 100 mg/day due to asymptomatic heart rate less than 50 bpm. The clinical and surgical characteristics of the groups are described in Tables 1, 2 and 3. Table 4 presents the results of the values of Tn I with 1 hour and 12 hours of arrival in the ICU between the control and beta-blockers. TnI values were lower in the beta-blocker group than in the control group. Table 2. Quantitative variables, comparison of the control and betablocker groups. Control Mean ± SE 59.0 ± 1.7 Age (years) 72.3 ± 3.0 Weight (Kg) 1.63 ± 1.0 Height (m) 26.7 ± 0.8 BMI (Kg/m2) Risk index – EUROSCORE 02.1 ± 0.3 Ejection fraction 64.0 ± 1.0 Pre-operative heart rate 73.8 ± 1.7 Variables

Control N (%) 11 (33)

Beta-blocker N (%) 11 (31)

P-value

23 (70) 04 (12) 02 (06) 04 (12) 12 (36) 01 (03) 0 11 (33) 25 (76) 18 (54) 08 (24) 05 (15)

27 (80) 01 (03) 04 (11) 02 (06) 16 (46) 0 02 (06) 12 (34) 25 (71) 25 (71) 05 (14) 08 (23)

0.312

P-value 0.619 0.519 0.330 0.740 0.757 0.153 0.021

SE= standard error; BMI= body mass index

Table 1. Qualitative variables, comparison of the control and betablocker groups. Variables Female Indication - Stable angina - Unstable angina - Anatomic - Silent schemia Prior infarction Prior revascularization Transient schemic attack Diabetes mellitus Hypertension Dyslipidemia Current smoking Family history of CoI

Beta-blocker Mean ± SE 57.9 ± 1.4 74.8 ± 2.4 1.65 ± 1.0 27.1 ± 0.8 02.0 ± 0.3 66.3 ± 1.1 68.0 ± 1.7

Table 3. Surgical characteristics in the control and beta-blocker groups.

0.867

Control Beta-blocker P-value group group Mean ± SE Mean ± SE Perfusion time (minutes) 86.8 ± 5.2 84.1 ± 5.1 0.705 Cross clamp time (minutes) 60.3 ± 3.0 57.0 ± 3.6 0.477 ICU stay (hours) 45.4 ± 1.4 54.3 ± 6.2 0.181 Number of grafts performed 3.0 (2.0-3.0) 3.0 (2.0-3.0) 0.215 Variables

0.434 0.299 0.163 0.934 0.686 0.149 0.554 0.419

Table 4. Analysis of troponin I results (ng/ml) in both groups. Troponin I Pre-operative At 1 hour At 12 hours

N= number of patients; CoI= coronary insufficiency

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Control Group Beta-blocker Group Median (25%-75%) Median (25%-75%) 0.5 (0.5-0.5) 0.5 (0.5-0.5) 2.7 (1.2-5.0) 2.1 (1.0-4.2) 3.7 (2.2-9.9) 2.5 (1.9-4.9)

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P-value 0.303 0.360 0.048

Rossi Neto JM, et al. - Myocardial protection with prophylactic oral metoprolol during coronary artery bypass grafting surgery: evaluation by troponin I

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However, this difference was only statistically significant in the 12 hours postoperatively data (2.50 versus 3.70, P=0.048). The changes of TnI were analyzed 12 hours post-operative and their association with some clinical and surgical variables. In addition to the variable group, univariate analysis showed that the factors to be correlated with the release of TnI 12 hours were perfusion time, cross clamp time and the number of grafts performed (Table 5). Although statistically significant, this relationship was considered weak by analyzing the values of correlation (R).

There was no significant difference in relation to postoperative complications in the ICU and in-hospital events between groups (21% in the control group versus 14% in patients with beta-blocker, P=0.454) (Table 6). In the final model of the multivariate analysis, the variables that have shown to be independent predictors of TnI release after 12 hours were: no beta-blockers administration and number of grafts required. Table 7 shows the percentage increase and the results expected. No beta-blockers administration increases in 22% the expected value of troponin 12 hours and for each graft required adds a 33% increase.

Table 5. Correlation between troponin I at 12 hours of postoperative and variables which could influence its release. Variable Weight Height BMI (body mass index) Age Ejection fraction Preoperative heart rate Perfusion time Cross clamp time Number of grafts performed

Correlation (R) -0.10 0.02 -0.17 0.06 -0.10 0.11 0.30 0.30 0.36

DISCUSSION

P-value 0.379 0.886 0.160 0.622 0.557 0.466 0.016 0.011 0.003

The results of this study prospectively evaluated 68 patients undergoing isolated CABG revealed for the first time in literature, a myocardial injury reduction in the group using oral beta-blocker at a dose of 200 mg/day for at least 72 hours preoperatively. Some demographic characteristics in the general population of the study should be highlighted as the presence of women in one third of patients, average age below 60 years, more than a third with previous myocardial infarction, diabetes

Table 6. Comparison of complications in the intensive care unit and hospital events between the control and beta-blocker groups. Variables Complications in the ICU - Inotropic agents > 24 hours - Temporary pacemaker - Intubation > 48 hours - ICU > 48 hours - Stroke - Atrial fibrillation - ICU deaths - Total complications in the ICU Hospital events - Hospital deaths - Total hospital events

Control Group n (%)

Beta-blocker Group n (%)

P-value

0 01 (03) 01 (03) 04 (12) 01 (03) 03 (09) 00 06 (18)

03 (09) 0 03 (09) 05 (14) 01 (03) 01 (03) 01 (03) 05 (14)

0.085 0.299 0.332 0.792 0.966 0.275 0.328 0.457

01 (03) 07 (21)

01 (03) 05 (14)

0.966 0.454

n= number of patients; ICU= Intensive Care Unit

Table 7. Results of the multivariate analysis of troponin I release at 12 hours.

Control group Number of grafts performed Hospital events Perfusion time Postoperative complications

Expected Percentage Increase 1.22 1.33 1.65 1.00 0.64

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CI 95%

P-value

1.02-1.46 1.01-1.77 0.97-2.80 0.99-1.01 0.36-1.14

0.027 0.046 0.063 0.077 0.132

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mellitus with a third, more than 70% with hypertension, more than 50% with dyslipidemia and all with ventricular function regarded as good. This population was considered low risk (mean EuroSCORE 2.0). Clinical characteristics were distributed equally in both groups, except for preoperative heart rate, which was lower in the beta-blocker group (73.8 versus 68.2, P=0.035). The myocardial injury is associated with cardiac surgery and can be caused by different mechanisms, including: direct trauma by suturing and manipulation of the heart; regional or global ischemia by inadequate cardiac protection, coronary dissection, microvascular events related to reperfusion or failure to perform the grafts [6]. Moreover, no biological marker is able to distinguish the injury caused by infarction that occurs in small quantities in myocardial cells, which usually are associated with the procedure itself [6]. However, the higher the value for a cardiac biochemical marker after the procedure, the greater the myocardial injury, regardless of the mechanism of injury. Despite the difficulties in interpreting the troponin level after a CABG, it is known that the higher this value, the worse the prognosis [7,8]. In this study, patients who used beta-blockers had a significant reduction in the levels of cTnI (2.50 ng/ml versus 3.70 ng/ ml, P=0.048), with a trend in the reduction of hospital events, despite not achieving statistical significance (14% versus 21%, P=0.454). It was also shown that the longer the perfusion time, the anoxic time, and the number of grafts required, the higher levels of TnI at 12 hours postoperatively. However, in multivariate analysis, independent predictors of troponin release were the number of grafts required and the fact of not using beta-blockers (control group). The clinical significance of this minimum or expected TnI amount has not yet been elucidated. In this study, despite the lower release in the beta-blocker group, there was no significant difference in relation to in-hospital events, probably because the study was not designed with this objective and the sample size was insufficient. On the other hand, the main interest of this study was to observe the behavior changes of TnI with a single prophylactic pharmacological intervention. Therefore, we excluded those who had a specific diagnostic criteria for perioperative myocardial infarction (presence of new Q waves on postoperative) known to elevate a lot the level of TnI. The use of a simple method of myocardial protection, as the use of prophylactic oral metoprolol, combined with new advances in surgical techniques and postoperative care, can further reduce the minimum expected release of markers of myocardial necrosis and thus possibly improve prognosis in CABG. The mechanisms of myocardial protection of beta-blockers in CABG are not yet fully understood. Animal experiments suggest that beta-blockade is cardioprotective during reperfusion, either by reduction in infarct size, improvement of ventricular function, reduction in apoptosis or decrease of

myocardial edema [9,10]. The possible mechanisms involved in this protection include reducing the release of oxygen free radicals and adhesion to endothelium nuclear polymorphs (major source of inflammatory response) [11]. During cardiac surgery with extracorporeal circulation there is a significant increase in the levels of catecholamines, resulting in an acute desensitization of beta-adrenergic receptors induced by these agonists. It is a cause of myocardial depression that occurs after surgery [12]. Probably the mechanisms of myocardial protection with the use of metoprolol are related, in part, with reductions of some ischemic process or metabolic changes that occur after surgery. There are no data in the literature to confirm whether reduced levels of TnI are the result of minor trauma straight from the heart with the use of beta-blockers, and what role of this mechanism in myocardial injury and its clinical relevance. Limitations of this study include being a single center, there is no standardization of the available tests for troponin, using intermittent clamping as surgical technique (and not be applied to other techniques) and cases of infarction without Q-wave in post-CABG are not identified, since there is no definition for diagnosis in clinical studies. This study used a low-risk population, and therefore with lower prevalence of hospital events, which may have contributed to no statistical differences between the groups. Finally, a larger sample of patients could extend the results obtained, but as the hospital morbidity and mortality are considered low in low-risk patients undergoing CABG surgery, multicenter clinical trials would be needed with a very large population to assess reduction of infarction postoperatively and hospital events with the use of prophylactic beta-blockers in addition to the impact of the minimum TnI changes in the possible risk factors and prognosis. There is a need to clarify whether changes of TnI in non-complicated patients with new Q waves on EKG have any clinical consequences after discharge, because this study was limited to in hospital follow up. The clinical implications of this study allow us to assure that there is some degree of myocardial injury even in uncomplicated patients and it becomes mandatory, therefore to define which the minimum reference value of cTnI is after CABG and correlate the values with prognosis. The reduction of TnI in the beta-blocker group in this study may help to understand the benefits of this medication, since it is known that the higher the levels of troponin, the worse the prognosis of patients, regardless of the pathophysiological mechanisms involved [8,13]. CONCLUSION The results of this research in isolated CABG, not complicated by the presence of new Q waves on EKG, comparing the release of TnI with 12 hours postoperative between the control group and who used oral prophylactic metoprolol

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for at least 72 hours, allow us to conclude that there was less myocardial injury in the beta-blocker group, conferring myocardial protection.

5. Roques F, Michel P, Goldstone AR, Nashef SA. The logistic EuroSCORE. Eur Heart J. 2003;24(9):881-2. 6. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60(16):1581-98.

Authors’ roles & responsibilities

7. Lurati Buse GA, Koller MT, Grapow M, Bolliger D, Seeberger M, Filipovic M. The prognostic value of troponin release after adult cardiac surgery: a meta-analysis. Eur J Cardiothorac Surg. 2010;37(2):399-406.

JMRN Protocol design, data collection, discussion of results and manuscript writing CG Discussion of results RFR Discussion of results AFSA Surgical procedures and discussion of results MI Surgical procedures and discussion of results VLA Data collection and discussion of results JJD Discussion of results LSP Protocol design, discussion of results and manuscript writing

8. Domanski MJ, Mahaffey K, Hasselblad V, Brener SJ, Smith PK, Hillis G, et al. Association of myocardial enzyme elevation and survival following coronary artery bypass graft surgery. JAMA. 2011;305(6):585-91. 9. Usta E, Mustafi M, Straub A, Ziemer G. The nonselective betablocker carvedilol suppresses apoptosis in human cardiac tissue: a pilot study. Heart Surg Forum. 2010;13(4):E218-22. 10. Fannelop T, Dahle GO, Matre K, Moen CA, Mongstad A, Eliassen F, et al. Esmolol before 80 min of cardiac arrest with oxygenated cold blood cardioplegia alleviates systolic dysfunction. An experimental study in pigs. Eur J Cardiothorac Surg. 2008;33(1):9-17.

REFERENCES 1. Leal JCF, Braile DM, Godoy MF, Purini Neto J, Paula Neto A, Ramin SL, et al. Early evaluation of cardiac troponin I in patients submitted to myocardial revascularization. Rev Bras Cir Cardiovasc. 1999;14(3):247-53.

11. Geissler HJ. Reduction of myocardial reperfusion injury by high-dose beta-blockade with esmolol. Thorac Cardiovasc Surg. 2002;50(6):367-72.

2. Califf RM, Abdelmeguid AE, Kuntz RE, Popma JJ, Davidson CJ, Cohen EA, et al. Myonecrosis after revascularization procedures. J Am Coll Cardiol. 1998;31(2):241-51.

12. Booth JV, Landolfo KP, Chesnut LC, Bennett-Guerrero E, Gerhardt MA, Atwell DM, et al. Acute depression of myocardial beta-adrenergic receptor signaling during cardiopulmonary bypass: impairment of the adenylyl cyclase moiety. Duke Heart Center Perioperative Desensitization Group. Anesthesiology. 1998;89(3):602-11.

3. Ong HT. Beta blockers in hypertension and cardiovascular disease. BMJ. 2007;334(7600):946-9. 4. Kaw R, Hernandez AV, Masood I, Gillinov AM, Saliba W, Blackstone EH. Short- and long-term mortality associated with new-onset atrial fibrillation after coronary artery bypass grafting: a systematic review and meta-analysis. J Thorac Cardiovasc Surg. 2011;141(5):1305-12.

13. Taniguchi FP, Pego-Fernandes PM, Jatene FB, Kwasnicka KL, Strumz CMC, Oliveira SA. Implicação prognóstica da creatinoquinase miocárdica e troponina na revascularização do miocárdio. Rev Bras Cir Cardiovasc. 2003;18(3):210-6.

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Lourenço IS, et al. - PressureARTICLE support-ventilation versus spontaneous breathing ORIGINAL with “T-Tube” for interrupting the ventilation after cardiac operations

Pressure support-ventilation versus spontaneous breathing with “T-Tube” for interrupting the ventilation after cardiac operations Pressão de suporte ventilatório versus respiração espontânea em “Tubo-T” para a interrupção da ventilação após as operações cardíacas

Isabela Scali Lourenço1, MSc; Aline Marques Franco1, MSc; Solange Bassetto1; Alfredo José Rodrigues1, MD, PhD

DOI: 10.5935/1678-9741.20130075

RBCCV 44205-1497

Abstract Objective: To compare pressure-support ventilation with spontaneous breathing through a T-tube for interrupting invasive mechanical ventilation in patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: Adults of both genders were randomly allocated to 30 minutes of either pressure-support ventilation or spontaneous ventilation with “T-tube” before extubation. Manovacuometry, ventilometry and clinical evaluation were performed before the operation, immediately before and after extubation, 1h and 12h after extubation. Results: Twenty-eight patients were studied. There were no deaths or pulmonary complications. The mean aortic clamping time in the pressure support ventilation group was 62 ± 35 minutes and 68 ± 36 minutes in the T-tube group (P=0.651). The mean cardiopulmonary bypass duration in the pressure-support ventilation group was 89 ± 44 minutes and 82 ± 42 minutes in the T-tube group (P=0.75). The mean Tobin index in the pressure support ventilation group was 51 ± 25 and 64.5 ± 23 in the T-tube group (P=0.153). The duration of intensive care unit stay for the pressure support ventilation group was 2.1 ± 0.36 days and 2.3 ± 0.61 days in the T-tube group (P=0.581). The atelectasis score in the T-tube group was 0.6 ± 0.8 and 0.5 ± 0.6 (P=0.979) in the pressure support ventilation group. The study

groups did not differ significantly in manovacuometric and ventilometric parameters and hospital evolution. Conclusion: The two trial methods evaluated for interruption of mechanical ventilation did not affect the postoperative course of patients who underwent cardiac operations with cardiopulmonary bypass.

Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto (FMRP-USP), Ribeirão Preto, SP, Brazil.

Correspondence address: Alfredo José Rodrigues Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto Departamento de Cirurgia e Anatomia. Av, Bandeirantes, 3.900, Campus Universitário-Monte Alegre Ribeirão Preto, SP, Brazil - Zip code: 14048-900 E-mail: alfredo@fmrp.usp.br

Descriptors: Pulmonary ventilation. Extracorporeal circulation. Ventilator weaning. Resumo Objetivo: Comparar a pressão de suporte ventilatório com a respiração espontânea em “Tubo-T” para interrupção da ventilação invasiva em pacientes submetidos à operação cardíaca. Métodos: Adultos de ambos os sexos foram alocados para pressão de suporte ventilatório por 30 minutos ou o mesmo período de ventilação espontânea com “Tubo-T” antes da extubação. Realizou-se manovacuometria, ventilometria e avaliação clínica antes da operação, imediatamente antes e após a extubação, 1h e 12h após extubação. Resultados: Vinte e oito pacientes foram estudados. Não ocorreram mortes ou complicações respiratórias. O tempo de pinçamento da aorta no grupo suporte ventilatório foi 62 ± 35

1

Work carried out at Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), Ribeirão Preto, SP, Brazil.

Article received on August, 31th, 2012 Article accepted on September 2nd, 2013

No financial support.

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“Tubo-T”, 64,5 ± 23 (P=0,153). O tempo na unidade de terapia intensiva para o grupo suporte ventilatório foi 2,1 ± 0,36 dias e para o grupo “Tubo-T”, 2,3±0,61 dias (P=0,581). O escore de atelectasia para o grupo “Tubo-T” foi 0,6 ± 0,8 e para o suporte ventilatório foi 0,5 ± 0,6 (P=0,979). Não houve diferença significativa na evolução clínica e nos valores de gasometria, manovacuometria e ventilometria entre ambos os grupos. Conclusão: O método utilizado para testar a adequação da interrupção da ventilação mecânica invasiva não afetou a evolução pós-operatória dos pacientes submetidos a operações cardíacas com circulação extracorpórea.

Abbreviations, acronyms & symbols CPB Cardiopulmonary bypass EP Expiratory maximal pressure IMV Invasive mechanical ventilation IP Inspiratory maximal pressure PSV Pressure support ventilation SIMV Synchronized intermittent mandatory ventilation

minutos e de 68 ± 36 minutos para o “Tubo-T” (P=0,651). O tempo de CEC no grupo suporte ventilatório foi 89 ± 44 minutos e para o “Tubo-T” de 82 ± 42 minutos (P=0,75). O índice de Tobin para o grupo suporte ventilatório foi 51 ± 25 e para o grupo

Descritores: Ventilação pulmonar. Circulação extracorpórea. Desmame do respirador.

INTRODUCTION

Ribeirão Preto Medical School, University of São Paulo (HCFMRP-USP) and was approved by the Ethics Committee (process number 5672/2006).

Invasive mechanical ventilation (IMV) is often essential in the first hours after cardiovascular operations as patients recover from anesthesia and reestablish homeostatic balance. When IMV is no longer required, the respiratory therapist and the physician must decide the most appropriate method to interrupt IMV. A simple and widespread method to determine whether a patient tolerates the discontinuation of ventilatory support is a trial of spontaneous breathing [1,2]. According to the III Brazilian Consensus on Mechanical Ventilation this trial is straightforward and effective way to wean off IMV [3]. However, the spontaneous breathing trial has been replaced by other techniques, mainly by pressure support ventilation (PSV) and synchronized intermittent mandatory ventilation (SIMV) [4]. These techniques are optional modes of ventilatory support provided by modern ventilators, which are especially useful for weaning patients recovering from pulmonary dysfunctions who require prolonged IMV. Yet, there is limited evidence that such methods of transition from IMV are superior to spontaneous breathing through a T-tube followed by extubation [1], especially in patients with good cardiopulmonary reserve. Therefore, this study aims to compare PSV with a spontaneous breathing trial using a T-tube for weaning from IMV in patients who underwent cardiovascular operations to correct valve dysfunction and/or coronary artery bypass grafting surgery. We considered weaning as the transition from controlled ventilation to spontaneous breathing before extubation.

Patients We recruited 30 patients with coronary artery disease and/ or valve disease, of both genders and older than 18 years-old. The basic protocols of perioperative care were not modified, with the exception of procedures for extubation. The volunteers were randomized according to a random number table generated by StatMate GraphPad 1.01 (GraphPad Software, Inc, San Diego, CA, USA). The StatMate software generated a random sequence of 15 numbers “1” (T-tube group) and 15 numbers “2” (PSV group). The first patient to participate in the study was allocated to the group corresponding to the first number generated, the second patient to the group corresponding to the second randomly generated number and so on. The exclusion criteria were postoperative bleeding requiring reoperation in the immediate postoperative period, ejection fraction ≤0.40, postoperative hemodynamic instability precluding extubation, not understanding the procedures proposed and refusal to participate in the study at any stage. Study groups The PSV group was comprised of patients who underwent a period of PSV for 30 minutes before interruption of IMV. These patients were extubated immediately after the IMV period with PSV. The T-tube group was comprised of patients who were disconnected from the ventilator when they met the criteria for interrupting the IMV then kept under spontaneous ventilation with their tracheal tube connected to a T-tube while receiving supplemental oxygen for 30 minutes before extubation. Clinical history, baseline measurements of blood

METHODS This prospective randomized trial was conducted in the Division of Thoracic and Cardiovascular Surgery of the

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pressure, heart rate, respiratory rate, minute volume, tidal volume, vital capacity, peak flow, maximal inspiratory pressure, and expiratory pressure were obtained from all patients before surgery. All patients underwent conventional chest physical therapy consisting of diaphragmatic breathing exercises associated with active and/or active-assisted mobilization of the upper and lower limbs. In addition, all patients participated in daily respiratory therapy sessions including cough, lung expansion maneuvers and airway clearance techniques training twice a day in the preoperative and postoperative periods. The protocol for postoperative analgesia was the same for all patients. Postoperatively all the patients received IMV using a Savina ventilator (Dräger, Lübeck, Germany) with SIMV, 12– 14 bpm, inspiration/expiration ratio of 1:2, PEEP of 5 cmH2O, tidal volume of 8 mL/kg body weight, and inspired fraction of O2 to maintain arterial oxygen saturation above 95% (pulse oximetry). Before interrupting the IMV, arterial gasometry and hemodynamic parameters were checked. All evaluations were performed in the preoperative period, immediately before extubation, and 1 and 12 hours after extubation. All patients had daily follow-ups until hospital discharge. The criteria for interrupting IMV were: a) patient should be conscious and cooperative; b) PaO2: 80–100 mmHg, arterial saturation >95%, pH: 7.35–7.45, and PaCO2: 35-45 mmHg; c) tidal volume ≥4 mL/kg; and d) inspired fraction of O2 ≤0.4. The Tobin index [5] was calculated for both groups before extubation. Patients in the PSV group who fulfilled the criteria for interrupting IMV were submitted to 30 minutes of pressure support ventilation of 10 cmH2O. Patients in the T-tube group who fulfilled the criteria for interrupting IMV were allowed to breath spontaneously through their tracheal tube connected to a T-piece and received supplemental O2 (aerosol with 0.9% saline and oxygen flow to 10L/min) for 30 minutes. At the end of the trial period, a blood sample for gasometric analysis was collected and ventilometric and hemodynamic parameters were measured. The patients were then extubated. A clinical and laboratory evaluation was performed again 1 and 12 hours after extubation. A physician, blinded to the study, compared the preoperative chest radiograph with a radiograph obtained in the morning after the operation. The following scores and criteria were used to grade lung atelectasis: 0) no abnormality: no image suggestive of atelectasis; 1) laminar atelectasis: linear opacities located mainly in lung bases; 2) segment atelectasis: opacities compatible with pulmonary segments; 3) lobar atelectasis; and 4) whole lung atelectasis.

were used for continuous variables with normal distribution, otherwise we used the Mann-Whitney or Wilcoxon test. For comparing proportions, we used the Fisher exact test. To compare intra-and inter-group repeated measurements (three or more), we used a two-way ANOVA; the first measurement was obtained postoperatively, or the pre-operative measure, when available, served as the control/baseline against which the later measurements were compared. Statistical analysis was performed using SPSS software version 18.0 (SPSS Inc., Chicago, IL, USA) with a significance level of 0.05. RESULTS Clinical characteristics Data from 28 patients, 14 in each group, were analyzed. One patient in the PSV group was excluded due to postoperative bleeding requiring reoperation, and one patient in the T-tube group who needed prolonged (>24h) invasive ventilation due to hemodynamic instability was excluded. The demographic data are shown in Table 1. There were no significant differences between groups. In the PSV group, 10 (71%) patients underwent revascularization and 4 (29%) underwent valve surgery. In the T-tube group, 11 (78%) patients underwent revascularization, two (14%) had valvular surgery and one underwent revascularization plus valvular surgery. The differences in the distribution of type of surgery were not significant (P=0.648). Table 1. Clinical characteristics. Variable "T-Tube” PSV N = 14 N = 14 Age (y)* 58 ± 9 53 ± 9 Gender (n, %) male 7 (50%) 10 (71.4%) Weight (kg)* 73.25 ± 9.83 74.79 ± 18.45 Height (m)* 1.65 ± 0.11 1.65 ± 0.07 BMI (kg/m2)* 27.1 ± 3 27.6 ± 6.6 Risk factors (n,%) Functional class NYHA 2 (15.4%) 1 (7.7 %) Class III/IV 9 (69.2%) 11 (84.6%) Arterial hypertension 6 (46.2%) 2 (15.4%) Diabetes mellitus 4 (30.8%) 3 (23.1%) Smoking 3 (23%) 0 (0%) Renal dysfunction 1 (7.7%) 0 (0%) COPD 2 (15.4%) 1 (7.7%) Peripheral vascular disease 8 (61.5%) 5 (38.5%) Myocardial infarction 0.58 ± 0.12 0.55 ± 0.17 Ejection fraction Systolic pulmonary pressure > 40 mmHg 2 (15.4%) 2 (15.4%)

Statistical analysis The results were expressed as mean ± standard deviation or percentages. The Shapiro-Wilk test was used to determine the data distribution (normality). Paired or unpaired “T” tests

P 0.193 0.440 0.793 0.983 0.812 0.539 0.645 0.202 0.658 0.220 0.308 0.539 0.434 0.628 0.715

Mann-Whitney Test and Exact Fisher test. BMI = body mass index; COPD = chronic obstructive pulmonary disease; NYHA = New York Heart Association

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The mean aortic clamping time of the PSV group was 62 ± 35 minutes and 68 ± 36 minutes in the T-tube group (P=0.651, Mann-Whitney test). The mean cardiopulmonary bypass (CPB) times were 89 ± 44 minutes and 82 ± 42 minutes in the PSV and T-tube groups, respectively (P=0.75, Mann-Whitney test). The mean Tobin index immediately before extubation in the PSV group was 51.1 ± 25 and 64.5 ± 23 in the T-tube group (P=0.153).

Postoperative ventilatory parameters In both groups the minute volume, tidal volume, vital capacity and peak expiratory flow declined significantly postoperatively, compared with the preoperative period (Figure 1). There was a significant decrease in both groups in the inspiratory (IP) and expiratory (EP) maximal pressures after extubation compared with preoperative values (Figure 2). However, we found that the IP was significantly lower in the PSV group (P=0.024). Notably, patients in this group already had a significantly lower IP preoperatively (P=0.028). As a result, the temporal pattern was similar in both groups, since there was no interaction between groups (P=0.150). Similar to the IP, the mean preoperative maximum EP was significantly lower in the PSV group (P=0.035). The differences between groups were not statistically significant (P=0.068) and the temporal pattern was similar in both groups (P=0.133). There were significant changes in the postoperatively respiratory rate, heart rate, PaO2 and arterial oxygen saturation compared to the preoperative values, but the temporal patterns were similar in both groups and the differences were not significant (Figure 3).

Clinical and radiologic postoperative evolution The mean duration of stay in the postoperative intensive care unit was 2.1 ± 0.36 days in the PSV group and 2.3 ± 0.61 days in the T-tube group (P=0.581, Mann-Whitney test). The mean duration of hospital stay for the PSV and T-tube groups, respectively, was 9.6 ± 4.83 days and 8.6 ± 2.8 days (P=0.829, Mann-Whitney test). There were no deaths and no patient required reintubation. One patient (T-tube group) experienced renal dysfunction, which was managed without dialysis (P=0.308). Forty-three percent of the patients had some degree of atelectasis. The mean atelectasis score in the T-tube group was 0.6 ± 0.8 and 0.5 ± 0.6 in the PSV group (P=0.979, Mann-Whitney test).

Fig. 1 - Perioperative evolution of the minute volume, tidal volume vital capacity and expiratory peak flow. Preo-op: preoperative; BW: before weaning; BE: before; 1h AE: 1 hour after extubation; 12h AE: 12 h after extubation

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Lourenço IS, et al. - Pressure support-ventilation versus spontaneous breathing with “T-Tube” for interrupting the ventilation after cardiac operations

DISCUSSION We found that there was no significant difference in weaning from IMV using a trial period of either PSV or spontaneous breathing using a T-tube piece in low-risk patients who underwent valve and/or coronary artery bypass grafting surgery. The main goal of a weaning trial is to identify patients who are able to breathe without a ventilator with the minimum risk of extubation failure and its potential complications [6]. Even though many institutions that perform cardiovascular surgery have routinely used pressure support as a weaning trial before extubation, there is no consensus that a specific method of weaning is superior. The majority of patients can be successfully weaned from mechanical ventilation irrespective of whether this is executed by intermittent mandatory ventilation, pressure support, or a T-tube trial [7,8]; a spontaneous breathing trial using a T-tube is still routinely performed in patients who fulfill weaning criteria [9]. A study reported by IMV Esteban et al. [10], which compared four methods of weaning, found that once-daily trials of spontaneous breathing led to about three times more rapid extubation than intermittent mandatory ventilation and was about twice as rapid as PSV. There are hospitals

Fig. 2 - Perioperative evolution of the maximal inspiratory and expiratory pressures. Preo-op: preoperative; 1h AE: 1 hour after extubation; 12h AE: 12 h after extubation

Fig. 3 - Perioperative evolution of the respiratory rate, heart rate, PO2 and arterial oxygen saturation. Preo-op: preoperative; BW: before weaning; BE: before; 1h AE: 1 hour after extubation; 12h AE: 12 h after extubation

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in developing countries that may have limited resources and/or more simple mechanical ventilators. Therefore, in a resource limited setting more rapid weaning might result in more efficient use of scarce ventilators and a shorter period of intubation related discomfort. PSV is a form of ventilatory support provided during IMV in which a predetermined, constant, positive inspiratory pressure is maintained by the ventilator, while the patient controls the respiratory cycle. In this ventilatory mode the patient controls the respiratory rate, the inspiratory flow, and the inspiration/expiration ratio, thereby reducing the oxygen demand as a consequence of reduced respiratory muscle work. It also provides a better synchrony between patient and ventilator [11,12]. Although the use of pressure support has been justified by reducing the imposed work of the ventilator circuit and the endotracheal tube [13], the use of even low levels of pressure support may lead to an underestimation of the risk of extubation failure [8]. Hence, a spontaneous breathing trial using a T-tube might be especially interesting in a population in which the risk of reintubation is particularly high [14]. The present study demonstrated that several parameters of respiratory function were lower in the first hours after extubation than they were preoperatively. These declines resulted primarily from pain and changes related to the anesthesia, CPB and the use of mechanical ventilation, as observed by other investigators [15-18]. Thus, even though spontaneous breathing with a T-tube may be an adequate method for weaning from mechanical ventilation in the majority of the cases, the method might confer a higher risk for reintubation [19], especially in patients with less cardiorespiratory reserve. Extubation failure seems to be determined more by the conditions inherent to the patient than by the method of weaning from the ventilator [9,20,21]. Pain, a major factor in the postoperative period [22], induces ventilation with smaller amplitude in an attempt to minimize discomfort. Moreover, the residual effect of anesthetic drugs and analgesics on the central nervous system also contributes to this breathing pattern. However, the respiratory parameters tend to improve gradually in the subsequent hours after surgery. The two methods for interruping IMV that we evaluated had no influence on the postoperative evolution of such parameters. The significant difference of maximal inspiratory pressures that we observed between the groups was probably caused by the fact that patients in the T-tube group had higher ventilatory pressure preoperatively; however there was no apparent effect on the postoperative evolution in favor of this group. Additionally, there was no significant difference in the Tobin index [5] between the groups, ensuring a safe interruption of IMV; hence, the expected extubation success was similar for both groups. The incidence of pulmonary complications in the

postoperative period of heart surgery depends on the diagnostic technique. Vargas et al. [23], in a prospective study using chest computed tomography scans, found that 86.7% of the patients who underwent CABG had some degree of pulmonary atelectasis in the second postoperative day. We believe that in our study the incidence of atelectasis was lower due to the lower sensitivity of chest radiographs to detect atelectasis. However, the extent of atelectasis, as measured by atelectasis scores, did not differ significantly between the methods used for interrupting the IMV, even though the PSV method had a greater theoretical potential to reduce the incidence and/or severity of atelectasis. Postoperative pulmonary atelectasis is multifactorial: anesthesia, cardiopulmonary bypass, type of operation performed, preoperatively pulmonary function and mode and the duration of IMV play a role. It is unlikely that a short trial period of pressure support ventilation or spontaneous breathing without airway pressure before extubation would noticeably influence the incidence of postoperative pulmonary atelectasis in patients with good cardiopulmonary functional reserve. Although we believe our study contributes to demonstrate the safety of using T-tube supported spontaneous breathing for weaning from IMV after cardiac surgery, it is not free of limitations. It is a study with a small sample of low-risk patients with good cardiopulmonary reserve, whose mean age was below 60 years old, and with uneventful operations. Because changing from mechanical to spontaneous ventilation increases preload and afterload [24] and because cardiac dysfunction is probably one of the most common causes of weaning failure [25,26], studies with larger numbers of patients at higher risk of cardiac and/or pulmonary dysfunction, including the elderly (≥ 65 years), are required to evaluate the methods for weaning from IMV in patients undergoing cardiovascular operations with greater external validity. In conclusion, our results showed that in low-risk patients who underwent cardiac surgery with cardiopulmonary bypass the method used to interrupt invasive mechanical ventilation, a short trial of either spontaneous breathing through a T-tube or pressure support ventilation, did not significantly affect the postoperative course.

Authors’ roles & responsibilities ISL Author AMF Co-author SB Co-author AJR Co-author

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2. Piotto RF, Maia LN, Machado MN, Orrico SP. Effects of the use of mechanical ventilation weaning protocol in the Coronary Care Unit: randomized study. Rev Bras Cir Cardiovasc. 2011;26(2):213-21.

como contribuinte o prejuízo na função pulmonar em pacientes submetidos à cirurgia cardíaca. Rev Bras Cir Cardiovasc. 2006;21(4):386-92. 16. Matte P, Jacquet L, Van Dyck M, Goenen M. Effects of conventional physiotherapy continuous positive airway pressure and non-invasive ventilatory support with bilevel positive airway pressure after coronary artery bypass grafting. Acta Anaesthesiol Scand. 2000;44(1):75-81.

3. Goldwasser R, Farias A, Freitas EE, Saddy F, Amado V, Okamoto V. III Consenso Brasileiro de Ventilação Mecânica. Desmame e interrupção da ventilação mecânica. J Bras Pneumol. 2007;33(Supl 2):S128-S36. 4. Gambaroto G. Fisioterapia respiratória em unidade de terapia intensiva. 1ª ed. São Paulo: Atheneu; 2006.

17. Pasquina P, Merlani P, Granier JM, Ricou B. Continuous positive airway pressure versus noninvasive pressure support ventilation to treat atelectasis after cardiac surgery. Anesth Analg. 2004;99(4):1001-8.

5. Tobin MJ. Predicting weaning outcome. Chest. 1988;94(2):227-8. 6. Frutos-Vivar F, Esteban A, Apezteguia C, González M, Arabi Y, Restrepo MI, et al. Outcome of reintubated patients after scheduled extubation. J Crit Care. 2011;26(5):502-9.

18. Wynne R, Botti M. Postoperative pulmonary dysfunction in adults after cardiac surgery with cardiopulmonary bypass: clinical significance and implications for practice. Am J Crit Care. 2004;13(5):384-93.

7. Esteban A, Aláa I, Gordo F, Fernández R, Solsona JF, Vallverdú I, et al. Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation. The Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med. 1997;156(2 Pt 1):459-65.

19. Assunção MSC, Machado FR, Rosseti HB, Penna HG, Serrão CCA, Silva WG, et al. Evaluation of T tube trial as a strategy of weaning from mechanical ventilation. Rev Bras Ter Intensiva. 2006;18(2):121-5.

8. Tobin MJ. Extubation and the myth of “minimal ventilator settings”. Am J Respir Crit Care Med. 2012;185(4):349-50.

20. Epstein SK, Ciubotaru RL, Wong JB. Effect of failed extubation on the outcome of mechanical ventilation. Chest. 1997;112(1):186-92.

9. Thille AW, Harrois A, Schortgen F, Brun-Buisson C, Brochard L. Outcomes of extubation failure in medical intensive care unit patients. Crit Care Med. 2011;39(12):2612-8.

21. Mokhlesi B, Tulaimat A, Gluckman TJ, Wang Y, Evans AT, Corbridge TC. Predicting extubation failure after successful completion of a spontaneous breathing trial. Respir Care. 2007;52(12):1710-7.

10. Esteban A, Frutos F, Tobin MJ, Alía I, Solsona JF, Valverdú I, et al. A comparison of four methods of weaning patients from mechanical ventilation. Spanish Lung Failure Collaborative Group. N Engl J Med. 1995;332(6):345-50.

22. Mueller XM, Tinguely F, Tevaearai HT, Revelly JP, Chioléro R, von Segesser LK. Pain location, distribution, and intensity after cardiac surgery. Chest. 2000;118(2):391-6.

11. Annat G, Viale JP. Measuring the breathing workload in mechanically ventilated patients. Intensive Care Med. 1990;16(7):418-21.

23. Vargas FS, Uezumi KK, Jatene FB, Terra-Filho M, Hueb W, Cukier A, et al. Acute pleuropulmonary complications detected by computed tomography following myocardial revascularization. Rev Hosp Clin Fac Med S Paulo. 2002;57(4):135-42.

12. Mancebo J, Amaro P, Mollo JL, Lorino H, Lemaire F, Brochard L. Comparison of the effects of pressure support ventilation delivered by three different ventilators during weaning from mechanical ventilation. Intensive Care Med. 1995;21(11):913-9.

24. Buda AJ, Pinsky MR, Ingels NB Jr, Daughters GT 2nd, Stinson EB, Alderman EL. Effect of intrathoracic pressure on left ventricular performance. N Engl J Med. 1979;301(9):453-9.

13. Brochard L, Rua F, Lorino H, Lemaire F, Harf A. Inspiratory pressure support compensates for the additional work of breathing caused by the endotracheal tube. Anesthesiology. 1991;75(5):739-45.

25. Cabello B, Thille AW, Roche-Campo F, Brochard L, Gómez FJ, Mancebo J. Physiological comparison of three spontaneous breathing trials in difficult-to-wean patients. Intensive Care Med. 2010;36(7):1171-9.

14. Thille AW, Cortés-Puch I, Esteban A. Weaning from the ventilator and extubation in ICU. Curr Opin Crit Care. 2013;19(1):57-64.

26. Caille V, Amiel JB, Charron C, Belliard G, Vieillard-Baron A, Vignon P. Echocardiography: a help in the weaning process. Crit Care. 2010;14(3):R120.

15. Giacomazzi MC, Lagni VB, Monteiro MB. A dor pós-operatória

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Bazan O, et al. - Laser Doppler anemometry measurements of steady flow ORIGINAL ARTICLE through two bi-leaflet prosthetic heart valves

Laser Doppler anemometry measurements of steady flow through two bi-leaflet prosthetic heart valves Velocimetria laser de escoamento permanente através de duas próteses cardíacas de duplo folheto

Ovandir Bazan1, Jayme Pinto Ortiz1, Francisco Ubaldo Vieira Junior2,3, Reinaldo Wilson Vieira2, Nilson Antunes2, Fabio Bittencourt Dutra Tabacow1, Eduardo Tavares Costa3, Orlando Petrucci Junior2

DOI: 10.5935/1678-9741.20130076

RBCCV 44205-1498

Abstract Introduction: In vitro hydrodynamic characterization of prosthetic heart valves provides important information regarding their operation, especially if performed by noninvasive techniques of anemometry. Once velocity profiles for each valve are provided, it is possible to compare them in terms of hydrodynamic performance. In this first experimental study using laser doppler anemometry with mechanical valves, the simulations were performed at a steady flow workbench. Objective: To compare unidimensional velocity profiles at the central plane of two bi-leaflet aortic prosthesis from St. Jude (AGN 21 – 751 and 21 AJ – 501 models) exposed to a steady flow regime, on four distinct sections, three downstream and one upstream. Methods: To provide similar conditions for the flow through each prosthesis by a steady flow workbench (water, flow rate of 17L/min.) and, for the same sections and sweeps, to obtain the velocity profiles of each heart valve by unidimensional measurements. Results: It was found that higher velocities correspond to the prosthesis with smaller inner diameter and instabilities of

flow are larger as the section of interest is closer to the valve. Regions of recirculation, stagnation of flow, low pressure, and flow peak velocities were also found. Conclusions: Considering the hydrodynamic aspect and for every section measured, it could be concluded that the prosthesis model AGN 21 - 751 (RegentTM) is superior to the 21 AJ – 501 model (Master Series). Based on the results, future studies can choose to focus on specific regions of the these valves.

University of São Paulo (USP), Polytechnic School, Mechanical Engineering Department, São Paulo, SP, Brazil. 2 University of Campinas (UNICAMP), Department of Surgery, Medicine Center and Experimental Surgery, Campinas, SP, Brazil. 3 University of Campinas (UNICAMP), Center for Biomedical Engineering, Campinas, SP, Brazil.

No financial support.

Descriptors: Heart valve prosthesis. Blood flow velocity. Laser-Doppler flowmetry. Resumo Introdução: A caracterização hidrodinâmica in vitro de próteses de válvulas cardíacas fornece informações importantes quanto ao seu funcionamento, sobretudo se realizada por meio de métodos não-invasivos de anemometria. Uma vez obtidos os perfis de velocidade para cada válvula, é possível compará-las quanto ao seu desempenho hidrodinâmico. Neste primeiro estudo experimental de anemometria laser com válvulas mecânicas,

1

Correspondence address: Ovandir Bazan Av. Prof. Mello de Moraes, 2231 – Cidade Universitária Armando de Salles Oliveira – São Paulo, SP, Brazil – Zip code: 05508-030 E-mail: ovandir.bazan@gmail.com

Hydrodynamic testing carried out at Department of Surgery, Medicine Center and Experimental Surgery,University of Campinas (UNICAMP), Campinas, SP, Brazil. Work paper carried out at Departamento de Engenharia Mecânica da Escola Politécnica da Universidade de São Paulo (PME-PUSP), São Paulo, SP, Brazil.

Article received on April 4th, 2013 Article accepted on September 16th, 2013

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Resultados: Verificou-se que as maiores velocidades correspondem à prótese de diâmetro interno menor e que as instabilidades do fluxo são maiores à medida que a seção de interesse encontra-se mais próxima da válvula. Também foram verificadas as regiões de recirculação, de estagnação do fluxo e de baixa pressão, além dos picos de velocidade para o escoamento em questão. Conclusões: Sob o aspecto hidrodinâmico e para todas as seções de interesse, foi possível concluir a preferência da válvula de modelo AGN 21 - 751 (RegentTM) sobre a 21 AJ – 501 (Master Series). Os resultados obtidos permitiram escolher, para os próximos trabalhos, um foco de estudo mais específico para regiões concretas dessas próteses.

Abbreviations, acronyms & symbols 1D Unidimensional 2D Bidimensional 3D Tridimensional LDA Laser Doppler anemometer

as simulações foram realizadas em bancada de testes para escoamento permanente. Objetivo: Comparar perfis de velocidade unidimensional no plano central de duas próteses aórticas de duplo folheto St. Jude (modelos AGN 21 – 751 e 21 AJ – 501) submetidas a um regime de fluxo permanente, para quatro seções distintas, três à jusante e uma à montante. Métodos: Proporcionar condições de similaridade para o escoamento através de cada prótese, por meio de bancada hidrodinâmica para escoamento permanente (água, à vazão de 17 L/ min.) e, por meio de anemometria laser unidimensional, obter os perfis de velocidades para as mesmas seções e varreduras.

Descritores: Próteses valvulares cardíacas. Velocidade do fluxo sanguíneo. Fluxometria por laser-Doppler.

INTRODUCTION

METHODS

In vitro hydrodynamic characterization of prosthetic heart valves provides important information regarding their operation [1,2], especially if performed by noninvasive techniques of anemometry [3-8]. Regarding hydrodynamic performance, it is possible to compare the velocity profiles for each valve and develop new designs. Velocity profiles are different for every type of valve and regions of flow stagnation and separation could occur, inducing formation of thrombosis, tissue overgrowth and/or calcification as well as blood hemolysis due to shear stress [1,9,10]. ISO 5840:2005 standard offers a pattern for the hydrodynamic performance testing of prosthetic valves, considering a steady or pulsatile flow and allowing for the evaluation of these valves [11,12]. Nevertheless, the comparison between prosthetic heart valves is possible under some conditions of flow similarity, which is the specific objective of this study: to compare the velocity profiles of two St. Jude bi-leaflet aortic valves with a nominal diameter of 21 mm exposed to a steady flow regime. The 1D velocity profiles were obtained at the central plane of flow, on four distinct sections, three downstream and one upstream of the valves. This first experimental study is due to an academic agreement established between UNICAMP (Medical School, Department of Surgery) and EPUSP (Polytechnic School, Mechanical Engineering Department). The study was developed at the Medicine Center and Experimental Surgery and the Biomedical and Environmental Engineering Laboratory, from the Medical School (UNICAMP) and Polytechnic School (EPUSP), respectively.

The objective of this study was to compare, during a steady flow regime, the velocity profiles at the central plane of two St. Jude bi-leaflet aortic valves. For this reason, it was necessary to establish a suitable methodology for experimental hydrodynamic testing. An academic agreement celebrated between EPUSP and UNICAMP made it possible to use the 1D LDA system, the steady flow hydrodynamic workbench, and the valve prostheses. The in vitro simulations presented in this paper did not have the purpose of reproducing the physiological conditions of the test fluid (blood analog properties of viscosity, density, and temperature), neither mimicking the physiological pressure and volumetric flow curves. The test fluid used was water at 27ºC and a steady flow condition was imposed in order to compare the velocity profiles of the two prostheses under the same range of volumetric discharge. In order to meet the specific purpose of this study (velocity profiles comparison), the ISO 5840:2005 guidelines [11] were not considered for the hydrodynamic performance analysis in steady flow regime (i.e., the imposition of volumetric flow discharge from 5 to 30 L/min., varying every 5 L/min.), although the unique imposed flow rate was close to the mean value established in those guidelines. Similarly, the question of the “effective orifice area” of the prostheses, discussed in the standard as criteria for the hydrodynamic performance analysis, was not addressed here. These characteristics, as well as pulsatile testing, are convenient and will be the target of next studies [13,14]. The materials and methods used in this study are presented below.

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Hydrodynamic workbench for steady flow regime The experimental workbench for the hydrodynamic testing in steady flow regime was designed at the Biomedical and Environmental Engineering Laboratory of EPUSP and was adapted at the Medicine Center and Experimental Surgery of UNICAMP. The workbench (Figure 1) consists of two reservoirs, an acrylic test chamber, sealing rings, three spherical valves, connections and pipes in PVC, and a positive displacement hydraulic pump with a nominal flow discharge of 360 gallons per hour (22.71 L/min). The same flow discharge was imposed for each experiment, allowing for the comparison of the velocity profiles obtained from the valves. An indirect method of volumetric flow measurement was used, by determining the effective flow of the pump once the steady state regime was performed on the hydrodynamic workbench. The effective pump flow discharge was obtained through variations in observed volume in a chamber of the experimental workbench during a certain period of time measured by a chronometer. With the experimental workbench adjusted for steady flow and with the hydraulic circuit to the testing chamber blocked (changing the valve in Figure 1, n.1, to the closed position), the filling up of the superior reservoir up to a stipulated height for a registered period of time was observed. The water volume was determined through the internal area of the base of the superior reservoir. The effective pump flow discharge was obtained dividing this volume by the measured time. The steady flow regime was performed when the water level in the reservoirs remained invariable. The same flow resistance in the hydraulic circuit (equivalent resistance) was

established for each experiment. Considering the differences between the two cardiac prostheses used, they offer distinct resistances to flow circulation, which implies different pressure distributions for each one (see the Results section). The equivalent flow resistance (total head loss) for each experiment was ensured by regulating the inferior spherical valve of the hydrodynamic workbench (Figure 1, n. 2). This spherical valve implies an adjustable flow resistance to the hydraulic circuit. To validate each experiment, the other two spherical valves (Figure 1, n. 1 and n. 3) remained , fully open and fully closed, respectively. In addition, the same total water volume was ensured on every testing. The effective flow value can be seen in the results section. In order to use the LDA system, a test chamber was conceived in a specific region of the hydraulic circuit (Figure 1, Detail A). The design of this test chamber is shown in Figure 2. It consists of two pipes and an optical confinement (Figure 2, n. 1), both in acrylic, and seal rings. The prosthesis (Figure 2, n. 4) is positioned under pressure, by longitudinal assembling of the two pipes, which in turn slide within the test chamber orifices. The two pipes downstream and upstream of the prosthesis (respectively, n. 2 and n. 3 in Figure 2) have internal diameters of 21.20 mm (able to shelter the chosen prosthesis) and both pipes are 210 mm long (upstream pipe length allows for the developed flow to be measured; downstream pipe length offers LDA measurements on different sections). Each pipe has one orifice to acquire pressure (Figure 2, n. 5) based on the height of the water column so that differential pressure can be obtained. When the pipes are positioned, they lock the prosthesis inside them. In this condition, the orifices are located 40 mm upstream and 20 mm downstream of the prosthesis.

Fig. 1 - Steady flow hydrodynamic workbench photo Highlighted: A (test chamber), 1 (top spherical valve), 2 (bottom spherical valve) and 3 (maintenance spherical valve)

Fig. 2 - Workbench test chamber detail Highlighted: 1 (optical confinement), 2 (upstream pipe), 3 (downstream pipe), 4 (bi-leaflet mechanical heart valve) and 5 (holes for differential pressure acquiring)

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Prostheses used The high frequency of valve replacement in the aortic position gave support to the choice of these prosthesis models in the research here presented [15-16]. Two St. Jude bi-leaflet prosthetic aortic valves, models 21 AGN – 751 (RegentTM) and 21 AJ – 501 (Masters Series), [17] were used. Although the two valves have the same nominal diameter of 21 mm, they have internal diameters of 19.6 mm and 16.7 mm, respectively. These prostheses models are shown in Figure 3. Considering dimensional variations of mechanical valves are negligible, only one prosthesis of each model was used in this study. So the results were considered independent of the number of samples. On the other hand, the internal diameter difference of the two prostheses (two different models) enabled the comparison and discussion of the results. Further studies are necessary to properly define the number of samples (prostheses).

volume at a particular intersection point. Since it is usually possible to separate three laser-beam wavelengths (violet, blue, and green) generated by the source, each wavelength can be manipulated in pairs of beams in orthogonal planes and it can provide information on up to three velocity components simultaneously: in each plane and for a specific point. This is why LDA systems are suitable for accurate velocity measurements. The most well-known configuration is called backscattering. In this configuration, the probes perform two simultaneous functions. Firstly, they are responsible for the convergence of monochromatic pairs of laser beams into the measurement point (intersection volume) through the outer lens (focusing lens). Secondly, they receive the scattered light (from seeding particles) through the inner lens (reception phase). When crossing the measurement volume, the seeding particles (contained in the flow) induce the scattering of light in varying intensity according to the flow velocity at that point. This returning light is redirected to the detection, signal conditioning, and processing phases. Finally, the results of the processing phase are manipulated and displayed using specific software. Thus, it is possible to know the velocity components of flow (1D, 2D, or 3D, depending on the system configuration) through sweeping points comprised of a linear sequence of measurement volumes. In this study, the LDA system of the Laboratory of Surgical Technique and Experimental Surgery at UNICAMP was used. The equipment is from Dantec Dynamics and it is actually capable of 1D velocimetry measurements only. This LDA system is based on Argon ions laser (Innova 70 Coherent, nominal power of 4 W), which is refrigerated by air with a backscattering configuration. The BSA Flow Software, from the same company, was also used. The scope of this study was the use of the 1D LDA system in order to obtain information about the horizontal plane of the flow. In addition, a manual traverse system was used for positioning the probe and, consequently, scanning the observed measurement points upstream and downstream of the prostheses.

Fig. 3 - Aortic bi-leaflet prosthetic heart valves used Highlighted: from left to right, models 21 AGN - 751 and 21 AJ - 501

LDA used: working principle and description Before describing the LDA system used, its working principle is briefly discussed. The laser Doppler anemometry system (or LDA) consists of a first stage of laser beam transmission so that pairs of laser beams converge into an intersection point, representing the point of interest to be measured (flow containing seeding particles). At the same time, another stage occurs, which is characterized by the detection of scattered light radiation from the small intersection volume (when particle motion is due to specific flow velocities). Then, these data can be conditioned and processed for a particular type of information, since the flashing light frequency (Doppler frequency) is proportional to the flow velocity at the measurement point. In the transmission phase, the purpose is to have the pairs of laser beams converging in order to form a measuring

RESULTS The 1D measurement results (one section upstream and three sections downstream of the valves) obtained for the two St. Jude bi-leaflet prosthetic aortic valves through a steady flow are presented. Introductorily, the flow conditions, which were derived from the operating workbench, as well as the proper positioning of the LDA probe, are presented below. Preliminary preparation The prostheses were arranged in the test chamber as described in the methodology. The test fluid used was water at 27°C, with the addition of seeding particles of 20 μm in

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diameter (Dantec Dynamics, Polyamide Seeding Particles). Plastic hoses were conveniently connected with a manometer in order to acquire differential pressure from the pipes’ orifices upstream and downstream of the prosthesis (Figure 2, n. 5). As mentioned in the methods section, the flow used in the test chamber was the pump’s effective flow, once both the same volume of water on the workbench and the steady flow regime on each experiment was established. The volumetric flow discharge was obtained indirectly: volume variation over measured time. This procedure was repeated three times and an arithmetic average was obtained. It was found that the flow rate imposed on the prosthesis was approximately 17 L/min. and this value represents the only possible flow discharge for the test chamber. With the LDA system in operation, the manual traverse system was referenced so that the laser beams always reached the mean horizontal plane of the pipes. A controlled routine established, via software, for the operation of the LDA system allowed some variables of the spectral analyzer to be controlled during the experiments, such as: the acquisition rate (up to 10 KHz), the photomultiplier voltage (up to 1,000 V), the amplifier signal gain (35 dB), and the operating power (170 mW). As described in the methods section, the LDA system operated only as 1D, through a probe with a pair of laser beams for the green spectrum and with the following characteristics: wavelength (ƛ) of 514.5 nm, diameter of 1.35 mm, focal length of 160 mm, spacing of the laser beam pair in the focal lens (frontals) of 38 mm, and fringes spacing (at the intersection volume of the beans) of 2.182 μm, with a total of 35 fringes. After establishing the horizontal plane for the reference position, the probe was positioned in the sections and points of interest, as shown in Figure 4. Following the flow direction, the first point of interest was

at 30 mm before the prosthesis (Figure 4, upstream). Three other points of interest were located after the prosthesis at 8 mm (Figure 4, downstream 1), 20 mm (Figure 4, downstream 2), and 32 mm (Figure 4, downstream 3). Therefore, the 1D LDA measurements consisted of scans of four sections for each prosthesis: one upstream and three downstream of the valve. Measurements in the hydrodynamic workbench After each prosthesis was assembled in the test chamber (Figure 2), the steady flow was established, and the probe was conveniently positioned facing the measurement point (Figure 4), the LDA system was used to obtain the 1D velocity profiles at the central plane along the inner diameter of the pipes (21.20 mm) and for four sections along flow direction. Every new measurement at the point of interest was obtained by displacing the LDA probe longitudinally through 0.50 mm over the horizontal diameter plane. Under 17L/min. of flow discharge, differential pressure was 42 mm of water column (or 3.09 mmHg) for assembling the prosthesis 21 AGN - 751 (internal diameter of 19.6 mm) and 63 mm of water column (or 4.63 mmHg) for the prosthesis 21 AJ - 501 (internal diameter of 16.7 mm). Figures 5 to 8 show the measured velocity profiles for the two prosthetic valve models, under steady flow conditions with a volumetric discharge of 17 L/min, for each point of interest. The discussion of the results is presented in the next section.

Fig. 5 - Velocity profiles at 30 mm upstream of the valves

DISCUSSION As stated in the methods section, the scope of this study does not address the guidelines of ISO 5840:2005 for hydrodynamic performance analysis. It only consists of accomplishing a comparison of the velocity profiles obtained for two models of valves with different internal diameters, under a common condition (volumetric discharge of 17 L/min.). Therefore, the prostheses provide different

Fig. 4 - Measurement sections referenced at the prosthesis positioning Highlighted: in the flow direction, upstream at 30 mm, downstream 1 at 8 mm, downstream 2 at 20 mm and downstream 3 at 32 mm from the valve

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flow restrictions in the passage of the flow, which implies different localized head loss. According to the literature, a prosthesis with larger diameter offers a smaller head loss. To ensure that in each of the experiments the same equivalent resistance was imposed on the hydraulic circuit, we used a spherical valve (Figure 1, n. 2). In fact, when the prosthesis with smaller diameter was used, this specific spherical valve was kept more open. Each velocity profile obtained at 30 mm upstream the valve allowed for the flow discharge to be estimated by integrating the velocity profile in the referenced area. This calculation confirms the previously measured value of 17 L/ min. with an error margin of approximately 5%. However, the testing by means of this single flow discharge represents an intrinsic limitation of this study [18]. The results obtained using the 1D LDA correspond to those expected from the literature: for all of the downstream measurement sections, greater velocities correspond to the prosthesis with a smaller internal diameter (16.7 mm, St. Jude model 21 AJ – 501), with higher transversal gradients near the pipe wall. In terms of pressure measurements, the prosthesis with a larger internal diameter (19.6 mm, St. Jude model 21 AGN – 751) presented smaller values of differential pressure and, consequently, smaller local head loss (42 mm of water column, or 3.09 mmHg). This implies smaller resistance to the passage of flow, compared with the prosthesis with a smaller diameter. In terms of flow instabilities downstream the prosthesis, it was observed that they are greater in the section near the prosthesis (section 1, downstream). It was found that although certain symmetry of the velocity profiles occurs, this symmetry is not significant. Some small negative values of velocity were measured with the LDA system. Recirculation zones were observed for both prosthesis models, St. Jude 21 AGN – 751 and St. Jude 21 AJ – 501, particularly in the downstream sections. Although negative values of velocity were expected in the prostheses surroundings, they were not expected at the farthest sections (downstream 2 and 3). The transversal gradients of velocity are much more pronounced in the case of the prosthetic valve with a larger diameter (St. Jude 21 AJ – 501), which is possible to observe by analyzing Figures 6 and 7. Similar future studies with measurements in more than one direction, i. e., 2D LDA measurements, will be used to validate the results obtained in this study. In terms of hydrodynamics, the prosthesis with a larger internal diameter should be adopted, considering the smaller peak velocities in the aortic root and the smaller transversal velocity gradients in this case, with less probability of recirculation. This is in accordance with the adequate sizing of the effective orifice area criteria so that residual stenosis after valve implantation can be avoided, thereby minimizing the occurrence of elevated pressure gradients through the valve [19]. On the other hand, the occurrence of

unsatisfactory pressure gradient across the prosthesis should also be avoided, as it would result in an incomplete reduction of the left ventricular hypertrophy [20,21]. Manufacturers have developed models of valves for different sutures without addressing controversies about the proper diameter of the prosthesis according to the patient's aortic annulus [19,20] and relying on the experience of clinical practice favoring hemodynamic performance.

Fig. 6 - Velocity profiles at 8 mm downstream of the valves

Fig. 7 - Velocity profiles at 20 mm downstream of the valves

Fig. 8 - Velocity profiles at 32 mm downstream of the valves

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This can be seen for the two St. Jude prostheses tested here. The AGN 21 - 751 (RegentTM) model is designed for supraannular suture and the AJ 21 - 501 (Masters Series) model for intra-annular suture. Currently, due to hemodynamic advantages, most surgeons employ the supra-annular positioning, even if there is a discrepancy among manufacturers regarding different internal diameter of the prostheses based on valves with the same nominal diameter [20-22]. For the prostheses studied here, which are from the same manufacturer, the choice of supra-annular prosthesis implies a valve with a larger inner diameter, although the two models have the same nominal diameter (21 mm). In fact, smaller peak velocities and a better hydrodynamic behavior were observed for all measurements of the supra-annular prosthesis 21 AGN – 751 (RegentTM) points of interest (Figures 6 to 8). However, it is not possible to disregard some surgical priorities that can be more relevant in some cases than the hydrodynamic aspects for a certain group of patients [20]. Clearly, the present study has some limitations because it does not include other flow ranges besides 17 L / min. [11, 18] and the LDA system available is restricted to 1D measurements. It would be feasible to extend this study by using another type of pump and including additional spherical valves and a flowmeter in the hydrodynamic circuit, so that it is possible to adjust other values of volumetric discharge in steady flow regime. As explained in the methodology, this will be the focus of the next study, using a cardiac simulator (USP), where 2D laser anemometry will be used for velocity measurements [13,14].

The authors also are grateful to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for the doctorate scholarship linked to the Programa de PósGraduação em Engenharia Mecânica of EPUSP.

Authors' roles & responsibilities OB

LDA equipment maintenance estimating; steady workbench design and manufacturing (except the test section of the prosthesis), test section CAD re-drafting; transfering and assembling of hydrodynamic workbench between USP and Unicamp; LDA training; LDA testing with the prostheses; paper writing, figures, graphs and resion; revisor replicas. JPO Academic partnership coordinator and linked jobs between USP and UNICAMP, LDA trials monitoring; line of research guiding at USP; paper revision and revisor replicas. FUVJ Workbench test section CAD drawings; test section manufacturing; LDA training; LDA testing with the prostheses; paper revision. RWV Academic partnership coordinator and linked jobs between USP and UNICAMP, LDA trials monitoring; line of research guiding at Unicamp; paper review. NA Responsible for resources finding, maintenance and restructuring of Medicine Center and Experimental Surgery Laboratory (LDA system); responsible for the heart valves obtainning from St. Jude Medical Brazil. FDBT Transfering and assembling of hydrodynamic workbench between USP and Unicamp; LDA training; LDA testing with the prostheses; testing photos. ETC Responsible for the workbench test section building (by the Center for Biomedical Engineering, CEB, Unicamp ) and enable the maintaining resources of the LDA equipment via CEB. OPJ Responsible for the Cardiac Surgery discipline at Unicamp and agreementing assignatures allowing the LDA maintenance.

CONCLUSION For the two prosthetic valves tested according the hydrodynamic aspect considered, it was possible to verify the superiority of the prosthesis model AGN 21 - 751 (RegentTM) comparing with model 21 AJ – 501 (Master Series). This choice implies the supra-annular positioning. The results permit to focus, in next work, the observations and measurements in some specific regions nearby the prosthesis were the flow recirculation and peak velocities occurs. According with was exposed in methods, for further testing will be possible include a statistical analysis based on a batch of valves and regarding some guidelines suggested by the ISO 5840:2005 standard.

REFERENCES 1. Yoganathan AP, He Z, Casey Jones S. Fluid mechanics of heart valves. Ann Rev Biomed Eng. 2004;6:331-62. 2. Dasi LP, Simon HA, Sucosky P, Yoganathan AP. Fluid mechanics of artificial heart valves. Clin Exp Pharmacol Physiol. 2009;36(2):225-37.

ACKNOWLEDGEMENTS

3. Chew YT, Chew TC, Low HT, Lim WL. Techniques in the determination of the flow effectiveness of prosthetic heart valves. In: Cardiovascular techniques: biomechanical systems: techniques and applications. vol. II. London:Cornelius Leondes, CRC Press LLC;2001. p.70-117.

This research had the support of: Faculdade de Medicina da UNICAMP, through Laboratório de Técnica Cirúrgica e Cirurgia Experimental, Escola Politécnica da USP (EPUSP), through Laboratório de Engenharia Ambiental e Biomédica (PME, LAB), and Centro Tecnológico de Hidráulica (CTH). The authors are grateful to these institutions for the infrastructure support during the research development.

4. Yoganathan AP, Chandran KB, Sotiropoulus F. Flow in prosthetic heart valves: state-of-the-art and future directions. Ann Biomed Eng. 2005;33(12):1689-94.

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5. Grigioni M, Daniele C, D’Avenio G, Morbiducci U, Del Gaudio C, Abbate M, et al. Innovative technologies for the assessment of cardiovascular medical devices: state-of-the-art techniques for artificial heart valve testing. Expert Rev Med Devices. 2004;1(1):81-93.

in vitro de próteses de válvulas cardíacas – testes preliminares de validação, em: 7º Congresso Latino Americano de Órgãos Artificiais e Biomateriais, COLAOB 2012, 2012, Natal/ RN, Proceedings of COLAOB 2012, disponível em: www.metallum. com.br/7colaob/resumos/trabalhos_completos/02-015.docx.

6. Meyer RS, Deutsch S, Bachmann CB, Tarbell JM. Laser Doppler velocimetry and flow visualization studies in the regurgitant leakage flow region of three mechanical mitral valves. Artif Organs. 2001;25(4):292-9.

15. De Paulis R, Schmitz C, Scaffa R, Nardi P, Chiariello L, Reul H. In vitro evaluation of aortic valve prosthesis in a novel valved conduit with pseudosinuses of Valsalva. J Thorac Cardiovasc Surg. 2005;130(4):1016-21.

7. Pinotti M. Is there correlation between the turbulent eddies size and mechanical hemolysis? J Braz Soc Mech Sci. 2000;22(4). Available from: URL: http://www.scielo.br/scielo. php?script=sci_arttext&pid=S0100-73862000000400006.

16. Dasi LP, Ge L, Simon HA, SotiropouloS F, Yoganathan AP. Vorticity dynamics of a bileaflet mechanical heart valve in an axisymmetric aorta. Phys Fluids. 2007;19(6):067105-17. 17. St. Jude Medical, Cardiac Surgery, U.S. Product Catalog, April 2010.

8. Meyer RS, Deutsch S, Maymir JC, Geselowitz DB, Tarbell JM. Three-component laser Doppler velocimetry measurements in the regurgitant flow region of a Björk-Shiley monostrut mitral valve. Ann Biomed Eng. 1997;25(6):1081-91.

18. Blais C, Pibarot P, Dumesnil JG, Garcia D, Chen D, Durand L-G. Comparison of valve resistance with effective orifice area regarding flow dependence. Am J Cardiol. 2001;88(1):45-52.

9. Lu PC, Lai HC, Liu JS. A reevaluation and discussion on the threshold limit for hemolysis in a turbulent shear flow. J Biomech. 2001;34(10):1361-4.

19. Dotta, F, Torres M, Manfroi W, Guaragna JCVC, Caramoni P, Albuquerque LC, et al. Desproporção prótese aórtica-paciente: definição, impacto e prevenção, Rev Bras Ecocardiogr. 2007;20(4):34-8.

10. Woo YR, Yoganathan AP. Pulsatile flow velocity and shear stress measurements on the St. Jude bileaflet valve prosthesis. Scand J Thorac Cardiovasc Surg. 1986;20(1):15-28.

20. Zhang M, Wu QC. Intra-supra annular aortic valve and complete supra annular aortic valve: a literature review and hemodynamic comparison. Scand J Surg. 2010;99(1):28-31.

11. American National Standard. Cardiovascular implants – cardiac valve prostheses, ISO 5840:2005.

21. Seitelberger R, Bialy J, Gottardi R, Seebacher G, Moidl R, Mittelöck M, et al. Relation between size of prosthesis and valve gradient: comparison of two aortic bioprosthesis. Eur J Cardiothorac Surg. 2004;25(3):358-63.

12. Cheade EL. Atualização de sistema duplicador de pulsos para teste de válvulas cardíacas [Dissertação de Mestrado]. Campinas: UNICAMP, Faculdade de Engenharia Elétrica e de Computação; 2008. 120p.

22. Guenzinger R, Eichinger WB, Hettich I, Bleiziffer S, Ruzicka D, Bauernschimitt R, et al. A prospective randomized comparison of the Medtronic Advantage Supra and St Jude Medical Regent mechanical heart valves in the aortic position: is there an additional benefit of supra-annular valve positioning? J Thorac Cardiovasc Surg. 2008;136(2):462-71.

13. Bazan O, Ortiz JP. Design conception and experimental setup for in vitro evaluation of mitral prosthetic valves. Rev Bras Cir Cardiovasc. 2011;26(2):197-204. 14. Bazan O, Ortiz JP. Sistema duplicador de pulsos para análise

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Custódio IL, et al. - Results ARTICLE of medium-term survival in patients undergoing ORIGINAL cardiac transplantation: institutional experience

Results of medium-term survival in patients undergoing cardiac transplantation: institutional experience Resultados de sobrevida a médio prazo em pacientes submetidos ao transplante cardíaco: experiência de uma instituição

Ires Lopes Custódio1, RN; Francisca Elisângela Teixeira Lima1, RN, PhD; Marcos Venícios de Oliveira Lopes1, PhD; Viviane Martins da Silva1, RN, PhD; João David Santos Neto1, MD; Maria do Perpétuo Socorro Martins1; Samya Coutinho de Oliveira1, RN

DOI: 10.5935/1678-9741.20130077

RBCCV 44205-1499

Abstract Introduction: The heart transplant became a consecrated therapy for patients with terminal heart failure, increasingly improving the survival. Objective: To identify the medium-term results in patients undergoing cardiac transplantation. Methods: This is a descriptive, documentary and retrospective study, using a quantitative approach, developed in a Unit of Transplant and Heart Failure, of a tertiary level public hospital, located in Fortaleza, CE, Brazil. The data were obtained from a sample of 188 patients (154 men and 34 women), submitted to the heart transplant, in the period from October 1997 to March 2011. There were calculated survival rates based on Kaplan-Meier methods. Results: There were identified information about the patient’s gender (male 81.91%), medical diagnosis which determined the heart transplantation (idiopathic cardiomyopathies 23.98%, ischemic 23.4% and Chagasic 17.02%). The median age of patients was 48 years old (interquartile range = 17.25 years) and the median observation period was 877 days. During this period, 78 patients died, resulting in survival ratios of 72%,

59% and 47% after 1, 5 and 9 years of cardiac transplantation, respectively. Younger patients had longer survival (P=0.0418). Conclusion: The medium-term survival of patients undergoing cardiac transplantation is significant, especially for younger patients.

Hospital de Messejana Dr. Carlos Alberto Studart Gomes, Fortaleza, CE, Brazil.

Correspondence address: Ires Lopes Custódio Avenida Frei Cirilo, nº 3480 – Cajazeiras – Fortaleza, CE, Brazil Zip code: 60864-190. E-mail: iresl.custodio@gmail.com

Descriptors: Heart transplantation. Survival rate. Mortality. Resumo: Introdução: O transplante cardíaco transformou-se em terapêutica consagrada para os doentes com insuficiência cardíaca em fase terminal, melhorando cada vez mais a sobrevida. Objetivo: identificar os resultados de sobrevida a médio prazo em pacientes submetidos ao transplante cardíaco. Métodos: Trata-se de um estudo descritivo, documental e retrospectivo, com abordagem quantitativa, desenvolvido em uma Unidade de Transplante e Insuficiência Cardíaca, de um hospital público de nível terciário, situado em Fortaleza, CE, Brasil. Os dados foram obtidos a partir de uma amostra de 188 pacientes (154 homens e 34 mulheres), submetidos ao transplan-

1

Work carried out at Hospital de Messejana Dr. Carlos Alberto Studart Gomes, Fortaleza, CE, Brazil.

Article received on April 24th, 2013 Article accepted on September 2nd, 2013

No financial support.

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pacientes foi 48 anos (Intervalo interquartílico = 17,25 anos) e a mediana do período de observação foi de 877 dias. Nesse período, 78 pacientes morreram, resultando em razões de sobrevida de 72%, 59% e 47% após 1, 5 e 9 anos do transplante cardíaco, respectivamente. Os pacientes mais jovens apresentaram maior tempo de sobrevida (P=0,0418). Conclusão: A sobrevida em médio prazo de pacientes submetidos ao transplante cardíaco é significativa, especialmente para os pacientes mais jovens.

Abbreviations, acronyms & symbols NYHA

New York Heart Association

te cardíaco, no período de outubro de 1997 a março de 2011. As taxas de sobrevida foram calculadas com base nos métodos de Kaplan-Meyer. Resultados: Identificaram-se informações sobre o sexo do paciente (81,91% masculino), diagnóstico médico que determinou o transplante cardíaco (miocardiopatias idiopática 23,98%, isquêmica 23,4% e chagásica 17,02%). A mediana da idade dos

Descritores: Transplante de coração. Taxa de sobrevida. Mortalidade.

INTRODUCTION

poor prognosis for survival are reduced ventricular ejection fraction, NYHA functional class III/IV, elevation of serum catecholamines, hyponatremia, elevated pulmonary capillary wedge pressure, decreased cardiac index, ventricular arrhythmias and maximal oxygen consumption (VO2 max) reduced during exercise [9]. Increases observed in cardiac transplant, new surgical techniques, immunosuppressive drugs, diagnostic methods and approaches of the multidisciplinary team in the early and late pre-and postoperative contribute to the survival of patients undergoing heart transplantation. These factors besides influencing the survival of patients still improve their quality of life as they recover physical capacity, return to work and even sports. As proof of that, in the first year, the survival rate is around 80% to 90% in five years 60% to 70% and 60% in ten years after the surgery [4,10-12]. Given these considerations, the aim of this study is to identify the medium-term outcomes in patients undergoing heart transplantation.

Cardiac transplantation between humans began at the University of Cape Town, South Africa, in 1967, with surgery performed by Bernard [1]. In 1968 Zerbini & Decourt [2] performed the first heart transplant in Latin America and the seventeenth in the world, in patients with dilated cardiomyopathy. Cardiac transplantation remains the treatment of choice for patients with refractory heart failure, despite the great improvement in life expectancy with clinical treatment, and for patients with end-stage heart failure, providing better survival. It is accepted as an effective method for the treatment of patients without hope, pleasure or satisfaction of a healthy and dignified existence, or at risk of death [3]. However, it cannot be considered an isolated event, but a process of continuous thread throughout the patient’s life [4]. The International Society for Heart and Lung Transplantation reported holding 76,538 orthotopic heart transplants in 352 centers in the world [5]. Brazil were recorded in 832 heart transplant procedures [6], showing that the country performs a high quantity of surgeries. Cardiac transplantation in the State of Ceará is only performed when the recipient is enrolled in the Unified Waiting List to receive the body [7]. Such receptors are patients with heart failure functional class III or IV New York Heart Association (NYHA) that are disabling with symptoms or at high risk of death in the first year and have no alternative to medical or surgical treatment [3]. However, there are limitations created by the higher number of receptors on the ongoing shortage of donors [8]. The increase of people placed on the waiting list for heart transplantation, is greater than those who are transplanted [7]. The success of heart transplantation depends on the quality of donor hearts. The assessment of these hearts is to ensure the maintenance of adequate hemodynamic conditions on the receiver and ensure their survival. Thus, the selection of transplant candidates should be careful with identification of risk factors and coexisting illnesses. The main factors of

METHODS This study examined the survival rates of patients undergoing heart transplantation. Data were obtained from the records of patients who were treated as outpatients in a public hospital that is reference to heart transplantation in a state in northeastern Brazil. The study included patients older than 18 years who underwent heart transplantation because of the following medical conditions: cardiomyopathies (dilated, idiopathic, Chagas disease, alcoholic, ischemic, valvular, hypertensive, hypertrophic, peripartum and viral), tachycardiomyopathy and retransplantation. Children and patients who did not submit complete data in the records of the transplant unit were excluded from the study. For data analysis, medical conditions frequently less than 10 were grouped into other heart conditions. Thus, most of the patients were male (81.9%) and had a median age at the start-up period of 48 years (interquartile range = 17.25 years). The three most common medical

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conditions that determine transplantation were idiopathic cardiomyopathy (23.9%), ischemic (23.4%) and chagasic (17.0%). The median follow-up was 877 days (interquartile range = 1802.8 days), and 58.5% of patients were alive when the study was terminated (Table 1). Statistical differences in age at transplant were identified by gender (P=0.0075, men=49, women=43), state (P=0.0334, alive=48.36; dead=44.47), and medical conditions (P<0.0001). Medical conditions also were related to gender (P=0.0489). Moreover, no relation was found between the condition of the patient at the end of analysis and medical conditions (P=0.3477) and gender (P=0.3573).

No statistical difference in survival times was identified in relation to gender (P=0.474) or medical conditions (P=0.352). On the other hand, the median survival time of patients who died was lower than that of patients alive at the end of the study period (113.5 vs. 1346.0, P<0.0001). No correlation was found between survival rates and age at transplant (rho=0.0171, P=0.8152). A total of 213 patients underwent heart transplantation since the first transplant in the institution. Of these, 24 were minors and one patient had incomplete data on their records and he could not be found. Thus, the records of a sample of 188 patients who underwent heart transplantation between October 1997 and March 2011 were assessed.

Table 1. Distribution of patients submitted to cardiac transplantation. Fortaleza, Ceará, Brazil. 2011 Variable 1. Gender Male Female 2. Etiology of cardiomyopathy Idiopathic cardiomyopathy Ischemic cardiomyopathy Chagas cardiomyopathy Dilated cardiomyopathy Alcoholic cardiomyopathy Valvular cardiomyopathy Other cardiac conditions 3. State of the patient Alive (censored) Dead Min. 19.00 0.0

4. Age (years) 5. Tracking time (days)

N

%

CI 95% Inf.

CI 95% Sup.

154 34

81.9 18.1

75.66 12.86

87.14 24.34

45 44 32 20 17 11 19

23.9 23.4 17.0 10.6 9.0 5.9 10.2

18.03 17.55 11.94 6.62 5.36 2.96 6.20

30.69 30.12 23.17 15.95 14.08 10.23 15.33

58.5 41.5 Average 46.75 1206

51.11 34.37 3o Q. Max. 55.25 73.00 1969 4449

110 78 1o Q. 38.00 166.2

Median 48.00 877

65.63 48.89 DP P Value* 12.06 0.0309 1183.4 <0.0001

* Shapiro-Wilk test; SD – standard deviation; CI - confidence interval

Table 2. Kaplan-Meier Estimators and Nelson-Aalen for the survival time of patients submitted to cardiac transplantation. Fortaleza, Ceará, Brazil. 2011 Time (Years) 0 ├┤1 1 ┤2 2 ┤3 3 ┤4 4 ┤5 5 ┤6 6 ┤7 7 ┤8 8 ┤9 >9

No of patients In risk

No of deaths

188 127 105 69 54 51 37 32 17 16

52 9 6 1 2 3 1 2 1 1

S(t) 0.719 0.666 0.626 0.617 0.594 0.556 0.541 0.503 0.473 0.444

EP* 0.03308 0.03505 0.03664 0.03721 0.03923 0.04229 0.04374 0.04859 0.05399 0.05815

Kaplan-Meyer CI 95% CI 95% Inf. Sup. 0.657 0.787 0.601 0.739 0.558 0.702 0.548 0.694 0.522 0.676 0.479 0.646 0.462 0.634 0.416 0.608 0.378 0.592 0.343 0.573

S(t) 0.720 0.667 0.627 0.618 0.595 0.558 0.543 0.505 0.476 0.447

* EP-standard error; CI - confidence interval

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EP* 0.03300 0.03498 0.03656 0.03713 0.03912 0.04214 0.04356 0.04829 0.05346 0.05748

Nelson-Aalen CI 95% CI 95% Inf. Sup. 0.658 0.788 0.602 0.739 0.559 0.703 0.549 0.695 0.523 0.677 0.481 0.647 0.464 0.636 0.419 0.609 0.382 0.593 0.348 0.575

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The outcome variable was defined as the time between the transplant and the occurrence of death or study closure. The condition of patients who remained alive at the closing date of the study was treated as censored data. Explanatory variables included gender, medical diagnosis that determined the need for transplantation, the patient’s age at transplant and patient status (alive or dead) at the time of the study survey. Data were assessed with the support of software R version 2.12.1. Absolute frequencies are presented, and the respective confidence intervals of 95% for qualitative variables. Quantitative variables are presented measures of central tendency (mean and median) and dispersion (standard deviation and quartiles). To check for normal distribution of quantitative variables was applied the Shapiro-Wilk test. In the event that the data were normally distributed, the means between groups were compared by Student’s t test. Otherwise, we used the Wilcoxon test or the Kruskal-Wallis test when more than two groups were compared. To assess the association between qualitative variables was applied the chi-square or Fisher’s exact test, depending on the expected frequencies calculated. Estimates of survival time were based on the methods of Kaplan-Meyer. For comparison of survival rates by sex and by patient status (censored/death) was applied to the Log-rank test. We performed a regression analysis according to the model of Cox proportional hazards to determine the influence of gender, medical conditions and age at transplantation on the survival ratio. The model fit was assessed by residual analysis Schoenfeld and Martingale. The level of statistical significance was 5%. This study was approved by the Research Ethics Committee of the institution, nº 774/10.

the survival curve of patients according to the Kaplan-Meyer. The median survival time estimated by the Kaplan-Meyer was 3268 days (approximately 6.6 years). Ten models were fitted to identify the variables that best explain the survival time of patients undergoing cardiac transplantation. The model that best performance variables included medical diagnosis, gender and age at transplant (P=0.0421).

RESULTS Estimates of the proportion of survivors generated using the Kaplan-Meyer show that survival rates fall at higher speed until the third year after transplantation (Table 2). Figure 1 depicts

Fig. 1 - Kaplan-Meier curve for the survival time of patients undergoing heart transplant

Table 3. Model from adjusted Cox proportional hazards survival data of patients undergoing heart transplantation. Fortaleza, Ceará, Brazil. 2011 Variables

Coef.

exp(Coef)

Idiopathic cardiomyopathy Chagasic cardiomyopathy Ischemic cardiomyopathy Dilated cardiomyopathy Alcoholic cardiomyopathy Valvular cardiomyopathy Gender (Female) Age

-0.399 -0.716 -0.198 -1.015 -0.581 0.140 0.071 -0.021

0.670 0.488 0.819 0.362 0.558 1.151 1.074 0.978

Confidence interval Inferior Superior 0.306 1.466 0.200 1.189 0.357 1.879 0.121 1.077 0.196 1.593 0.402 3.295 0.607 1.899 0.958 0.999

EP (Coef) 0.399 0.453 0.423 0.556 0.534 0.536 0.291 0.010

P value 0.3168 0.1147 0.6387 0.0679 0.2766 0.7929 0.8060 0.0418

R2 = 0.055; (maximum possible = 0.981); Test Likelihood Ratio = 10.6 (GL= 8; P=0.2252); Wald test = 10,87 (GL = 8; P=0.2089); Logrank test= 11,16 (GL = 8; P=0.1929)

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The analysis of Schoenfeld residuals showed that the presented model adopted proportionality of errors (P>0.05) for all variables and Martingale residual analysis showed that there were no outliers generated by the adjusted model compared to the observed data. The data model of Cox proportional hazards are presented in Table 3. However, it is observed that the model had a poor fit with only the age variable statistical significance at 5%, showing that younger people have a higher survival rate. Patients with dilated cardiomyopathy showed a reduced survival time significantly only at the level of 7%.

Rates of graft survival and patient from the United Network for Organ Sharing October 1987 to December 1994 in the United States (n=14.665) showed a graft survival: in one month, 91.4%, one year, 81.8%, 2 years 77.4%, 3 years to five years 73.4%, 65.7%. And patient survival: in one month, 92.0%, one year, 82.8%; 2 years, 78.6%; 3 years, 75.0%, and five years, 67.8%. These recipients were predominantly white (n=12,196), the others were black (n=1.429), Hispanic (n=610), Asian (n=148), and other unknown (n=282). Five-year survival was better in recipients of white (69.0%) than in other groups (blacks 60.0%, Hispanics 64.0%, Asians 63.9%) [21]. The medium-term survival of patients undergoing heart transplantation was significant, particularly for younger patients, and, consistent with results from another study, because despite the impact of age on outcomes of cardiac transplantation continue to be debated, especially regarding adequacy of heart transplantation in patients who are older than 60 or 65 years of age, in general, the worst results are seen in extremes of age, in patients with less than one year of age, and those over 65 years [11]. Research points out that the experience of recipient age greater than 50 years was not a risk factor for early mortality. There was, however, an increased risk for patients over 60 years of age, though the numbers were small, making it difficult statistical inference [22]. Another study shows that the age limit for heart transplantation is relative and difficult decision because biological factors have more influence than the actual chronological age [8]. Some risk factors can help in better selection of donors and recipients and direct new scientific investigations in the field of cardiac transplantation, survival and prognostic factors related to donor age above 40 years, especially in females, and ischemic stroke/hemorrhage as a cause of brain death, and the association of these three factors of poor prognosis. Recipients with cardiac operations have a higher early mortality related to vascular coagulopathy and neurological disorders [4]. It may be noted that 58.51% of patients undergoing heart transplantation were alive when the study was completed, showing the work done by a multidisciplinary team with deep knowledge of the prognosis and management of these patients. The selection of candidates for heart transplantation involves the use of prognostic variables to identify patients with advanced heart failure, combined with the contraindications and comorbidities, which can lead to unfavorable outcomes such as reduced survival after transplantation or high perioperative risk [23].

DISCUSSION In this study, most patients are male (81.9%). Similar results were found in other studies, in which most patients submitted to heart transplantation (81.8%) are male [4,11,13]. In another study with 156 patients enrolled in the Unified Waiting List of Cear谩 for heart transplantation, concluded that the highest percentage of males (81%), young adults aged between 20-40 years (22.4%) and middle-aged adults 40-64 years (56.4%), with an average of 36 years, had dilated cardiomyopathy (91%), 69% underwent transplantation, 25% died before transplantation and 6% were excluded due to improvement or worsening of symptoms and the average waiting time was 136 days until the day of cardiac transplantation [7]. The average age of patients in this study was 48 years. Found results similar to this study, with a mean age of 44.8 years [4], 44.9 years [13] and 46.9 years [12]. However, other studies showed a higher than average, with the average age of patients after transplantation of 52.0 [14] years and 54.0 years [15]. Thus, it was noticed that the majority of patients undergoing transplantation showed age considered productive, i.e., refers to the age at which the person has an occupation. In relation to etiology of cardiomyopathy frequently determined that heart transplantation were idiopathic cardiomyopathy (23.9%), ischemic (23.4%) and Chagas disease (17.0%). In similarity with a study that showed predominance in idiopathic dilated cardiomyopathy (39%), chagasic (26.5%), ischemic (24.2%) and other causes (10.3%) [16]. And disagreeing with other studies, which showed that cardiomyopathies motivated the transplantation were dilated (47.4%), Chagas disease (24.7%), ischemic (23.7%), valve (2.1%) and other cardiomyopathies [9,11,14,17]. According to the data of the indication and survival after heart transplantation , it was found in this study percentages of 72%, 59% and 47% after 1, 5 and 9 years, respectively. However, we found some studies demonstrated that survival after heart transplantation is around 72.7% in the first year, 61.5% at five years, 56.4% in seven and 60% in ten years in exercise capacity, return to work and quality of life of patients undergoing the procedure, when compared to conventional treatment of heart failure [3,8,18-20].

Limitations of the study Because the study used existing records in the institution, few variables were studied and registration bias may have influenced the estimates. Thus, other factors may influence survival in patients undergoing heart transplantation were not recorded and therefore were not included in the adjusted

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models. The sample size may also have influenced the estimates because some medical conditions that determined the need for transplantation showed small samples. Although it was identified a relationship between longer survival and the age of patients, no inference can be made for children or adolescents from this study. Moreover, few variables were assessed. There was no way to expand the analysis of the data, because data were available only who were recorded on the forms.

5. Aurora P, Boucek MM, Christie J, Dobbells F, Edwards LB, Keck BM, et al. Registry of the International Society for Heart and Lung Transplantation: tenth official pediatric lung and heart/lung transplantation report. J Heart Lung Transplant 2007;26(12):1223-8. 6. Brasil. Ministério da Saúde. Base de dados do DATASUS: procedimentos hospitalares-transplante cardíaco [online] 2008 a 2013. Acessed on 22/3/2013. Avaliable from: www.datasus. gov.br.

CONCLUSION

7. Lima FET, Ferreira AKA, Fontenele KA, Almeida ERB. Perfil dos pacientes na Lista Única de Espera para transplante cardíaco no estado do Ceará. Arq Bras Cardiol. 2010;95(1):79-84.

We identified that the medium-term survival in patients submitted to heart transplantation showed significant results, especially for younger patients. The median survival time was about six and a half years and a little over 40% of patients survive more than nine years after transplantation.

8. Areosa CMN, Almeida DR, Carvalho AC, Paola AAV. Avaliação de fatores prognósticos da insuficiência cardíaca em pacientes encaminhados para avaliação de transplante cardíaco. Arq Bras Cardiol. 2007;88(6):667-73.

Authors' roles & responsibilities

9. Fiorelli AI, Coelho GHB, Oliveira Junior JL, Oliveira AS. Heart failure and heart transplantation. Rev Med. 2008;87(2):105-20.

ILC

Data obtaining, analysis and interpretation, also in the draft and/ or critical revision, revision of the final version FETL Data obtaining, analysis and interpretation, drafting the outline, critical review and revision of the final version MVOL Data obtaining, analysis and interpretation, drafting the outline, critical review and revision of the final version VMS Data obtaining, analysis and interpretation, drafting outline, critical review and revision of the final version JDS Data obtaining, analysis and interpretation, drafting the outline, critical review and revision of the final version MPSM Data obtaining, analysis and interpretation, drafting the outline, critical review and revision of the final version SCO Data obtaining, analysis and interpretation, drafting the outline, critical review and revision of the final version

10. Bacal F, Souza-Neto JD, Fiorelli AI, Mejia J, Marcondes-Braga FG, Mangini S, et al. II Diretriz Brasileira de Transplante Cardíaco. Arq Bras Cardiol. 2010;94(1):e16-e76. 11. Jatene AD. Cirurgia da insuficiência cardíaca grave. São Paulo: Atheneu; 1999. 12. Fiorelli AI, Oliveira Junior JL, Stolf NAG. Cardiac transplantation. Rev Med. 2009;88(3):123-37.

REFERENCES

13. Branco JNR, Teles CA, Aguiar LF, Vargas GF, Hossne Jr MA, Andrade JCS, et al. Transplante cardíaco ortotópico: experiência na Universidade Federal de São Paulo. Rev Bras Cir Cardiovasc. 1998;13(4):285-94.

1. Bernard CN. The operation. A human cardiac transplant: an interim report of a sucessful operation performed at Groote Schuur Hospital, Cape Town. S Afr Med J. 1967;41(48):1271-4.

14. Antunes MJ, Prieto D, Sola E, Antunes PE, Oliveira JF, Franco F, et al. Cardiac transplantation: five year’s activity. Rev Port Cardiol. 2010;29(5):731-48.

2. Zerbini EJ, Decourt LV. Experience on three cases of human heart transplantation. In: Symposium Mondial Deuxiemé Level Heart Transplantation; 1969; Quebec. Annals of the 2nd World Symposium; 1969. p.179.

15. Silva EA, Carvalho DV. Transplante cardíaco: complicações apresentadas por pacientes durante a internação. Esc Anna Nery. 2012;16(4):674-81.

3. Bacal LF, Souza-Neto JD, Fiorelli AI, Mejia J, Marcondes Braga FG, Mangini S, et al. II Diretriz Brasileira de Transplante Cardíaco. Arq Bras Cardiol. 2009;94(Suppl 1):16-73.

16. Moraes-Neto F, Tenório D, Gomes CA, Tenório E, Hazin S, Magalhães M, et al. Transplante cardíaco: a experiência do Instituto do Coração de Pernambuco com 35 casos. Rev Bras Cir Cardiovasc. 2001;16(2):152-9.

4. Assef MAS, Valbuena PFMF, Neves Junior MT, Correia EBA, Vasconcelos M, Manrique R, et al. Transplante cardíaco no Instituto Dante Pazzanese de Cardiologia: análise da sobrevida. Rev Bras Cir Cardiovasc. 2001;16(4):289-304.

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17. Stehlik J, Edwards LB, Kucheryavaya AY, Aurora P, Christie JD, Kirk R, et al. The Registry of the International Society for Heart and Lung Transplantation: twentyseventh official adult heart transplant report--2010. J Heart Lung Transplant. 2010;29(10):1089-103.

21. UNOS. Annual Report: The US Scientific Registry of Transplant Recipients and the Organ Procurement and Transplantation Network. Transplant 19881995. Richmond VA: UNOS; and Rockville, MD: The Division of Transplantation, Bureau of Health Resources Development, Health Resources and Services Administration, US Department of Health and Human Services; 1996.

18. Moreira LFP, Galantier J, Benício A, Leirner AA, Fiorelli AI, Stolf NAG, et al. Perspectivas da evolução clínica de pacientes com cardiomiopatia chagásica listados em prioridade para o transplante cardíaco. Rev Bras Cir Cardiovasc. 2005;20(3):261-9.

22. Ibrahim M, Masters RG, Hendry PJ, Davies RA, Smith S, Struthers C, et al. Determinants of hospital survival after cardiac transplantation. Ann Thorac Surg. 1995;59(3):604-8.

19. Couto WJ, Branco JNR, Almeida D, Carvalho AC, Vick R, Teles CA, et al. Transplante cardíaco e infecção. Rev Bras Cir Cardiovasc. 2001;16(2):141-51.

23. Mehra M, Kobashigawa J, Starling R, Russell S, Uber P, Parameshwar J, et al. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates - 2006. J Heart Lung Transplant. 2006;25(9):1024-42.

20. Guimarães JI, Mesquita ET, Bocchi EA, Vilas-Boas F, Montera MW, Moreira MCV, et al. Revisão das II Diretrizes da Sociedade Brasileira de Cardiologia para o diagnóstico e tratamento da insuficiência cardíaca. Arq Bras Cardiol. 2002;79(supl 4):3-30.

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Pares DBS, etORIGINAL al. - Fetal heart assessment in the first trimester of pregnancy: ARTICLE influence of crown-rump length and maternal body mass index

Fetal heart assessment in the first trimester of pregnancy: influence of crown-rump length and maternal body mass index Avaliação do coração fetal no primeiro trimestre de gestação: influência do comprimento cabeça-nádega e índice de massa corporal materna

David Baptista Silva Pares1, MD, MSc, PhD; Angélia Iara Felipe Lima1, MD, MSc; Edward Araujo Júnior1, MD, MSC, PhD; Luciano Marcondes Machado Nardozza1, MD, MSC, PhD; Wellington P. Martins2, MD, PhD; Antonio Fernandes Moron1, MD, MSC, PhD DOI: 10.5935/1678-9741.20130078

RBCCV 44205-1500

Abstract Objective: To evaluate the influence of the crown-rump length and body mass index on sonographic evaluation of the fetal heart using abdominal and vaginal routes in the first trimester of pregnancy. Methods: We conducted a cross-sectional study with 57 pregnant women between 12-14 weeks (CRL≤ 84 mm). We evaluated the following fetal cardiac plans using the abdominal and vaginal routes: four-chamber view, right ventricle outflow tract, left ventricle outflow tract and aortic arch. We used the B-mode, color Doppler and four-dimensional ultrasonography (spatio-temporal image correlation). To evaluate the influence of crown-rump length and body mass index in the assessment of fetal cardiac planes, we used the t test unpaired. Results: There were no statistically significant differences in the rates of success and failure between abdominal and vaginal routes in relation to body mass index, however, there was a higher failure rate in vaginal assessment using B mode associated with color Doppler (P<0.01).

Conclusion: The crown-rump length and body mass index had no interference in fetal cardiac assessment in the first trimester of pregnancy.

Federal University of São Paulo (UNIFESP). São Paulo, SP, Brazil. Faculty of Medicine of Ribeirão Preto of the University of São Paulo (FMRP USP), Ribeirão Preto, SP, Brazil.

Correspondence address: Edward Araújo Júnior Obstetric Department of the Federal University of São Paulo (UNIFESP) Rua Napoleão de Barros, 875 – Vila Clementino, São Paulo, SP Brazil – Zip Code: 04024-002 E-mail: araujojred@terra.com.br

Descriptors: Fetal heart. Color Doppler. Ultrasonography, Doppler, Color. Crown-rump length. Body mass index. Resumo Objetivo: Avaliar a influência do comprimento cabeça-nádega e do índice de massa corporal na avaliação ultrassonográfica do coração fetal, pelas vias abdominal e vaginal, no primeiro trimestre de gestação. Métodos: Realizou-se um estudo de corte transversal com 57 gestantes normais entre 12 a 14 semanas (CCN ≤ 84 mm). Foram avaliados os seguintes planos cardíacos, pelas vias abdominal e vaginal: quatro câmaras, via de saída do ventrículo direito, via de saída do ventrículo esquerdo e arco aórtico. Utilizou-

1 2

This study was carried out at Fetal Cardiology Unit of the Obstetric Department of the Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. Gynecology and Obstetric Unit at the Ribeirão Preto Medical School, Universitu of São Paulo (FMRP- USP), Ribeirão Preto, SP, Brazil. Ultrasonography and Medical Recycling School of Ribeirão Preto (EURP), Ribeirão Preto, SP, Brazil.

Article received on April 28th, 2013 Article accepted on June 17th, 2013

No financial support.

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Resultados: Não se observou diferenças estaticamente significativas nas taxas de sucesso e insucesso entre as vias abdominal e vaginal em relação ao índice de massa corporal, contudo, observou-se maior taxa de insucesso na avaliação vaginal utilizando o modo B associado ao Doppler colorido (P<0,01). Conclusão: O índice de massa corporal e o comprimento cabeça-nádega não tiveram interferência na avaliação cardíaca fetal no primeiro trimestre de gestação.

Abbreviations, acronyms & symbols CRL CHD BMI STIC

crown-rump length Congenital Heart Disease Body Mass Index Spatio-temporal image correlation

se o modo B, Doppler colorido e ultrassonografia de quarta dimensão (spatio-temporal image correlation). Para avaliar a influência do comprimento cabeça-nádega e índice de massa corporal na avaliação dos planos cardíacos fetal, utilizou-se o teste t não-pareado.

Descritores: Coração fetal. Doppler colorido. Ultrassonografia Doppler em cores. Estatura cabeça-cóccix. Índice de massa corporal.

INTRODUCTION

vaginal and abdominal approaches, using B mode, color Doppler and STIC.

Congenital heart disease (CHD) are the most common birth defects, affecting 5-8 per 1,000 live births [1]. Early diagnosis of CHD allows better prenatal care and referral of pregnant women to tertiary center of cardiology and neonatal cardiac surgery. Fetal cardiac assessment through abdominal approach during the examination of screening for chromosomal defects in first trimester of pregnancy allows the evaluation of the four-chamber plane, and enable the diagnosis of 44.8% of CHD [2]. The vaginal ultrasound has been used for almost 20 years for fetal cardiac evaluation at the end of the first trimester of pregnancy, allowing the assessment of the fourchamber plane in addition to the extended examination [3]. The three-dimensional ultrasound using spatio-temporal image correlation (STIC) software has been used in the first trimester through the abdominal approach, demonstrating that cardiac volumes sent via an internet link allowed us to obtain standard cardiac planes [4]. The first trimester screening is important, not only for the calculation of risk for chromosomal defects, but also to correct dating of gestational age, assessment of some fetal malformations and determination of chorionicity in cases of twin pregnancies [5,6]. The body mass index (BMI) and crown-rump length (CRL) can be factors that influence fetal cardiac assessment in the first trimester through abdominal approach [7], however, there are no descriptions of the influence of these parameters in vaginal or STIC approaches. The aim of this study is to assess the influence of BMI and CRL in the assessment of fetal cardiac planes, through

METHODS We performed a prospective cross-sectional study with healthy pregnant women between 12 and 14 weeks of gestation, from July 2011 to July 2012. This study was approved by the Research Ethics Committee of the Federal University of São Paulo (UNIFESP), whereas women who agreed to participate signed a voluntary written informed consent. Inclusion criteria were singleton pregnancies, with measurement of CRL from 45 mm to 84 mm. We performed a single measure of CRL, which also served to the correct dating of gestational age. Patients were randomly selected, with the examinations in two Voluson 730 Expert and E8 devices (General Electric Healthcare, Zipf, Austria) equipped with volumetric convex (RAB4-8L) and endocardial (RIC5-9W) transducers. Cardiac assessment was performed by a single examiner (AIFL) immediately after the screening of the first trimester. Initially, we used the abdominal approach, associating the B mode to color Doppler, followed by vaginal approach. We aimed to obtain the plans of four heart chambers, left ventricular outflow tract and right ventricular outflow tract and aortic arch. In the plane of the four heart chambers, size, axis and symmetry of the chambers were assessed. In the plans of the right and left ventricular outflow tract, there was the crossing of the great vessels, in addition to the similarity of their diameters. The plane of the aortic arch allowed the identification of the descending aorta. We considered “successful” when all four planes were obtained

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by abdominal and/or vaginal and “unsuccessful” when obtaining three or fewer plans. After the two-dimensional evaluation, the assessment was performed by STIC associated with color Doppler. A fourdimensional assessment was performed immediately after the two-dimensional, starting with an abdominal approach, followed by vaginal. The acquisition of the STIC volumes was performed in the plane of the four heart chambers, wherever possible with the fetal back at 6h, with a scan time of 10 seconds and aperture angle of 20°. The maximum scan time for each method was 30 minutes. All women returned at the age between 20 and 24 weeks for completion of two-dimensional echocardiography, in order to confirm normal fetal heart anatomy. The women were not followed-up, not being obtained their neonatal outcomes. Statistical analysis was performed using SPSS software version 18.0 (SPSS Inc. Chicago, IL, USA). To assess the influence of BMI and CRL in fetal cardiac evaluation by abdominal and vaginal approaches, we used the unpaired t test. We used a significance level of P<0.05.

RESULTS We assessed 57 pregnant women between 12 and 14 weeks (19 patients in each gestational age) who agreed to participate in the study, and 4 were not included because they had not the CRL > 84 mm. Therefore, for final statistical analysis were considered 53 pregnant women. The average maternal age was 27.8 ± 5.5 years (range of 14-39 years). The average CRL was 71.5 ± 8.6 mm (range of 55.9 to 84 mm). The median maternal BMI was 23.8 ± 2.6 kg/m2 (range of 17.5 to 29.9 kg/m2). BMI did not influence the performance of the methods (B mode, color Doppler and STIC) when using the vaginal approach, but in the abdominal approach, although with no statistically significant differences, the findings suggest that it is more difficult for a satisfactory examination as BMI increases (Table 1). Regarding the CRL, there was greater failure rate in assessing through vaginal approach when using color Doppler and B modes (P<0.01) (Table 2).

Table 1. Review of significant difference between the mean body mass index and the success or failure of the method by vaginal/abdominal approaches B mode (vaginal) B mode + Color Doppler (vaginal) STIC (vaginal) B mode (abdominal) B mode + Color Doppler (abdominal) STIC (abdominal)

(BMI) Success 23.74 23.49 23.48 23.10 23.59 23.10

(BMI) Failure 23.89 24.00 24.15 24.29 24.02 24.47

P* 0.85 0.52 0.36 0.11 0.56 0.06

*unpaired t test; STIC: spatio-temporal image correlation, BMI: body mass index.

Table 2. Review of significant difference between the average crown-rump length and the success or not of the method by vaginal/abdominal approaches B mode (vaginal) B mode + Color Doppler (vaginal) STIC (vaginal) B mode (abdominal) B mode + Color Doppler (abdominal) STIC (abdominal)

(CRL) Success 69.78 66.78 69.32 73.51 73.95 71.73

(CRL) Failure 72.24 73.54 73.30 70.28 68.89 71.31

P* 0.34 <0.01 0.13 0.19 0.09 0.86

* unpaired t test; STIC: spatio-temporal image correlation; CRL: crown-rump length

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DISCUSSION

between 41 and 78 mm, the rate of success in getting all cardiac plans was only 58%. As limitation of the study, we noted that all pregnant women were randomly selected, so that the results were adversely affected due to the absence of women with BMI ≥ 30kg/ m2. Maybe if we had selected patients knowingly obese or with certain diseases prior to pregnancy such as diabetes mellitus we could infer the real impact of maternal BMI in assessing the quality of fetal cardiac examination in the first trimester of pregnancy.

In this study we assessed the influence of BMI and CRL in evaluating standardized cardiac planes between 12-14 weeks of gestation, through abdominal and vaginal approaches, through B mode, Color Doppler and spatio-temporal image correlation. To our knowledge, there are no studies in the literature with similar methodology. Obstetric oltrasonography of obese women is difficult and in some situations can become a real challenge for physicians. In a study comparing obese women (BMI ≥ 30kg/m2) versus non-obese pregnant women (BMI < 30kg/ m2) who underwent second trimester ultrasound, it was found that suboptimal visualization rates increased significantly in obese group, both for the heart (37% versus 19%) and fetal column (43% vs. 29%) [ 8]. In the first trimester, only one study assessede the influence of BMI on fetal cardiac evaluation [7]. In this study, 103 pregnant women between 11 and 13 weeks and 6 days were examined, through abdominal approach using B mode and, in some cases, associated with color Doppler. They did not found no influence of BMI in cardiac assessment (P=0.752) [7]. Similarly, in our study, assessing 54 pregnant women between 12 and 14 weeks, there was also no influence of BMI. One possible explanation would be the fact that at the end of the first trimester, most of the women maintains prepregnancy BMI, in addition, the mean BMI of our group was 23.8 kg/m2, and no pregnant woman had a BMI≥ 30kg/ m2. Other studies have reported the influence of maternal BMI as a visualization of the fetal heart in the first trimester of pregnancy [9-11]. Even the guideline of the American Institute of Ultrasound in Medicine (AIUM) for fetal cardiac evaluation refers to a technical limitation in the case of obese patients, due to acoustic shadows in the third trimester. They reported the need for assessments at different times, in addition to optimization of the device and focus adjustment, frequency, gain, magnification, temporal and harmonic [12] resolution. In relation to the influence of CRL, we observed failure rate statistically significant only for the group assessed by vaginal approach using color Doppler and B mode (P<0.01). In a previous study of the screening in the first trimester, the CRL showed a factor of influence on quality of nuchal translucency measurement [13]. Regarding fetal cardiac evaluation, there is only one study that assessed the influence of the CRL [7]. In this study, the authors observed no influence of CRL in fetal cardiac assessment (P=0.899), with a mean of CRL of 72.1 mm [7], however, it was performed only the assessment by laparotomy. In our study, the mean CRL was 71.5 mm and we used the abdominal and vaginal approaches in all cases. The higher failure rate in vaginal approach is due to the need for prior learning curve, plus the need for experienced examiners to obtain the standardized cardiac plans. In a study by Vimpeli et al. [ 14 ], who assessed 584 fetuses with CRL

CONCLUSION Concluding, we found no influence of the index of body mass and crown-rump length in fetal cardiac assessment between 12-14 weeks gestation. The assessment through vaginal approach needs more prior training, and experienced examiners in this pathway. Subsequent studies using populations of previously obese women are needed to prove the real influence of body mass index in fetal cardiac assessment in the first trimester of pregnancy. Authors' roles & responsibilities DBSP Main coordinatination AIFL Data collection EAJ Preparation of the article for publication LMMN Adjunct coordenation WPM Statistical analysis AFM Final review

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5. Novotná M, Hašlík L, Svabík K, Zizka Z, Belošovičová H, Břešťák M, et al. Detection of fetal major structural anomalies at the 1114 ultrasound scan in an unselected population. Ceska Gynekol. 2012;77(4):330-5.

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13. Zohav E, Dunsky A, Segal O, Peled R, Herman A, Segal S. The effects of maternal and fetal parameters on the quality of nuchal translucency measurement. Ultrasound Obstet Gynecol. 2001;18(6):638-40.

8. Hendler I, Blackwelll SC, Bujold E, Treadwelll MC,Wolfe HM, Sokoll RJ, Sorokin J. The impact of maternal obesity on midtrimester sonographic visualization of fetal cardiac and craniospinal structures. Int J Obes Relat Metab Disord. 2004;28(12):1607-11.

14. Vimpelli T, Huhtala H, Acharya G. Fetal echocardiography during routine first-trimester screening: a feasibility study in an unselected population. Prenat Diagn. 2006;26(5):475-82.

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Assad RS, et al. - ReversibleARTICLE pulmonary trunk banding. IX. G6PD activity of ORIGINAL adult goat myocardium submitted to ventricular retraining

Reversible pulmonary trunk banding. IX. G6PD activity of adult goat myocardium submitted to ventricular retraining Bandagem ajustável do tronco pulmonar. IX: atividade da G6PD do miocárdio de cabras adultas submetido ao treinamento ventricular

Renato Samy Assad1, MD, PhD; Leonardo Augusto Miana1,2, MD, PhD; Miriam Helena FonsecaAlaniz1, BPh, PhD; Maria Cristina Donadio Abduch1, VMD, PhD; Gustavo José Justo da Silva1,3, PE, PhD; Fernanda Santos de Oliveira1MD; Luiz Felipe Pinho Moreira1, MD, PhD; José Eduardo Krieger1, MD, PhD DOI: 10.5935/1678-9741.20130079

RBCCV 44205-1501

Abstract Objective: Increased glucose 6-phosphate dehydrogenase activity has been demonstrated in heart failure. This study sought to assess myocardial glucose 6-phosphate dehydrogenase activity in retraining of the subpulmonary ventricle of adult goats. Methods: Eighteen adult goats were divided into three groups: traditional (fixed banding), sham, and intermittent (adjustable banding, daily 12-hour systolic overload). Systolic overload (70% of systemic pressure) was maintained during a 4-week period. Right ventricle, pulmonary artery and aortic pressures were measured throughout the study. All animals were submitted to echocardiographic and hemodynamic evaluations throughout the protocol. After the study period, the animals were killed for morphological and glucose 6-phosphate dehydrogenase activity assessment. Results: A 55.7% and 36.7% increase occurred in the intermittent and traditional right ventricle masses, respectively,

when compared with the sham group (P<0.05), despite less exposure of intermittent group to systolic overload. No significant changes were observed in myocardial water content in the 3 groups (P=0.27). A 37.2% increase was found in right ventricle wall thickness of intermittent group, compared to sham and traditional groups (P<0.05). Right ventricle glucose 6-phosphate dehydrogenase activity was elevated in the traditional group, when compared to sham and intermittent groups (P=0.05). Conclusion: Both study groups have developed similar right ventricle hypertrophy, regardless less systolic overload exposure of intermittent group. Traditional systolic overload for adult subpulmonary ventricle retraining causes upregulation of myocardial glucose 6-phosphate dehydrogenase activity. It may suggest that the undesirable “pathologic systolic overload” is influenced by activation of penthose pathway and cytosolic Nicotinamide adenine dinucleotide phosphate availability. This altered energy substrate metabolism can elevate levels of free

Heart Institute (InCor), University of São Paulo Medical School, São Paulo, SP, Brazil 2 Medical School, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil 3 University of Maastricht. Mastricht, Netherlands.

Funding: SILIMED, Rio de Janeiro, RJ (donation of adjustable banding devices and molecular biology kits), FAPESP (research grant nº 2006/50831)

1

Correspondence address: Renato Samy Assad Heart Institute (InCor), University of São Paulo Medical School, Laboratory of Research in Cardiovascular Surgery (LIM-11) / Laboratory of Genetics and Molecular Cardiology Av. Dr. Enéas de Carvalho Aguiar, 44 – Cerqueira César - São Paulo, SP Brazil – Zip Code: 05403-000 E-mail: rsassad@cardiol.br

Work carried out at Heart Institute (InCor), University of São Paulo Medical School, São Paulo, SP, Brazil. Work awarded at the 39th Congress of the Brazilian Society of Cardiovascular Surgery, Maceió, April 2012, and at the 67th Brazilian Congress of Cardiology, Recife, September 2012. Presented at the 46th Annual Meeting of the Association for European Paediatric and Congenital Cardiology, Istanbul, May 2012.

Article received on April 14th, 2013 Article approved on August 19th, 2013

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Assad RS, et al. - Reversible pulmonary trunk banding. IX. G6PD activity of adult goat myocardium submitted to ventricular retraining

Métodos: Foram utilizadas 18 cabras adultas, divididas em três grupos: convencional (bandagem fixa), sham e intermitente (bandagem ajustável; 12 horas diárias de sobrecarga). A sobrecarga sistólica (70% da pressão sistêmica) foi mantida durante quatro semanas. As avaliações hemodinâmica e ecocardiográfica foram realizadas durante todo o estudo. Depois de cumprido o protocolo, os animais foram mortos para avaliação morfológica e da atividade da Glicose 6-Fosfato Desidrogenase dos ventrículos. Resultados: Apesar de haver sobrecarga sistólica proporcionalmente menor no ventrículo subpulmonar do grupo intermitente (P=0,001), ambos os grupos de estudo apresentaram aumento da massa muscular de magnitude similar. Os grupos intermitente e convencional apresentaram aumento da massa de 55,7% e 36,7% (P<0,05), respectivamente, em comparação ao grupo sham. O conteúdo de água do miocárdio não variou entre os grupos estudados (P=0,27). O ecocardiograma demonstrou maior aumento (37,2%) na espessura do ventrículo subpulmonar do grupo intermitente, em relação aos grupos sham e convencional (P<0,05). Foi observada maior atividade da Glicose 6-Fosfato Desidrogenase na hipertrofia miocárdica do ventrículo subpulmonar do grupo convencional, comparada aos grupos sham e intermitente (P=0,05). Conclusão: Ambos os grupos de treinamento ventricular desenvolveram hipertrofia ventricular, a despeito do menor tempo de sobrecarga sistólica no grupo intermitente. A maior atividade de Glicose 6-Fosfato Desidrogenase observada no grupo convencional pode refletir um desequilíbrio redox, com maior produção de fosfato de dinucleotídeo de nicotinamida e adenina e glutationa reduzida, um mecanismo importante da fisiopatologia da insuficiência cardíaca.

Abbreviations, acronyms & symbols ANOVA Analysis of variance Ao Aorta CCTGA Congenially corrected transposition of the great arteries COBEA Brazilian College of Animal Experimentation DW Dry weight ECG Electrocardiogram G6PD Glucose 6-phosphate dehydrogenase IVS Interventricular septum IW Initially weighed LV Left ventricle NADPH Nicotinamide adenine dinucleotide phosphate PT pulmonary trunk PTB Pulmonary trunk banding RV Right ventricle TGA Transposition of the great arteries

radicals by Nicotinamide adenine dinucleotide phosphate oxidase, an important mechanism in the pathophysiology of heart failure. Descriptors: Energy metabolism. Hypertrophy, right ventricular. Transposition of great vessels. Cardiac surgical procedures. Goats. Resumo Objetivo: O aumento da atividade miocárdica da Glicose 6-Fosfato Desidrogenase tem sido demonstrado na insuficiência cardíaca. Este estudo avalia a atividade miocárdica da Glicose 6-Fosfato Desidrogenase no treinamento do ventrículo subpulmonar de cabras adultas.

Descritores: Metabolismo energético. Hipertrofia ventricular direita. Transposição dos grandes vasos. Procedimentos cirúrgicos cardíacos. Cabras.

INTRODUCTION

mature myocardium induced by pulmonary trunk banding (PTB) in order to establish retraining protocols for a more “desirable” physiological hypertrophy. In physiological conditions, fatty acids, especially the long chain ones, act as the main myocardial energy substrate [5]. Fatty acid oxidation in mitochondria represents approximately 70% of all ATP production in a normal heart [6,7]. On the other hand, several studies have shown that there is greater preference for glucose oxidation by cardiac substrates in heart failure and in a hypertrophic heart [8,9]. However, the change in energy substrate varies according to the etiology and severity of the ventricular dysfunction, where the degree of metabolic modulation plays an important role in determining adaptive or maladaptive function in terms

Both adult and adolescent patients diagnosed with congenially corrected transposition of the great arteries (CCTGA) as well as those with transposition of the great arteries (TGA) who underwent either Senning or Mustard surgery can develop right ventricle dysfunction (systemic) [1,2]. Subpulmonary ventricular retraining for anatomical correction, in those patients, still presents disappointing results. Hypertrophy induced by acute pressure overload can lead to foci of cellular necrosis in the hypertrophied myocardium and, consequently, to late ventricular dysfunction [3,4]. At present, it is imperative to understand the molecular mechanisms involved in hypertrophy of the

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of states leading to pathological hypertrophy. G6PD is the first and rate-limiting enzyme in the pentose phosphate pathway, which is an alternate and independent pathway from glycolysis, generating nicotinamide adenine dinucleotide phosphate (NADPH) and pentose (ribose-5phosphate). It catalyzes the conversion of Glucose 6-Phosphate into 6-Phosphogluconolactone. The process is divided into two phases: generation of NADPH and non-oxidative synthesis of pentose. It maintains the level of the NADPH coenzyme, which in turn maintains the level of reduced glutathione, protecting the cells, in normal conditions, from oxidative lesions. Therefore, the more NADPH is needed, the greater the activity level of the G6PD enzyme. There is evidence that greater G6PD activity leads to increased production of superoxide radicals as well as oxidative stress in diabetes, heart failure, and hypertension. Previous studies of the energy metabolism of acute myocardial hypertrophy in young animals have shown an increase in G6PD activity associated with ventricular dysfunction in continuous systolic overload, compared to intermittent overload [10]. In the subset of the subpulmonary ventricle retraining of adult patients for the double switch operation , it would be also interesting to analyze changes in energy metabolism. This study sets out to evaluate qualitative differences in the process of myocardial hypertrophy induced by continuous and intermittent pressure overload, through biological markers such as G6PD, which show occasional phenotypic changes to the energy metabolism.

(Takaoka Fuji Maximus, São Paulo, SP), with inspired oxygen fraction between 60 and 100% and Isoflurane inhalation (1 to 2%). The goats were placed in the right lateral decubitus and monitored with continuous electrocardiogram (ECG) and invasive arterial pressure (auricular artery). Postoperative pain relief was obtained in the first three days by administering Tramadol chlorhydrate (2 mg/kg, intramuscular). Surgical Procedure The goats were prepared for the sterile procedure, as described in previous studies [11,12]. For animals in the Traditional group, pulmonary trunk (PT) banding was performed with cardiac tape (Polysuture, São Sebastião do Paraíso, MG), positioned about 10 mm above the valve. Animals in the Sham and Intermittent groups had an adjustable banding device implanted immediately above the pulmonary valve and fixed to the PT adventitia. The insufflation button was implanted and fixed subcutaneously in the thorax. Hemodynamic monitoring catheters were exteriorized and maintained filled with heparin. The following antibiotics were administered prophylactically to all animals: cefazolin (30 mg/Kg), gentamicin (4 mg/Kg), and Benzathine Penicillin (500,000 IU), intramuscular. The Benzathine Penicillin dose was repeated after two weeks. In addition, Heparin Sodium 5,000 IU was administered daily by subcutaneous injection until the end of the protocol. Description of the adjustable banding device The adult model device was developed in collaboration with SILIMED (Indústria de silicone e instrumental médicocirúrgico e hospitalar Ltda., Rio de Janeiro, RJ), as previously published [11,12]. It has an outer diameter of 24 mm and is 6 mm wide. The inner surface has a distensible silicon layer, 0.6 to 0.8 mm thick, whose expansion compresses the lumen of the PT according to the amount of liquid injected in the insufflation button. This button is implanted subcutaneously so that fine adjustments to the diameter of the banding ring can be made percutaneously.

METHODS This study was approved by the Ethics Committee for the Analysis of Research Projects at – InCor University of Sao Paulo Medical School (process: SDC 2660/05/080) and carried out in accordance with the regulations on the use of animals in teaching and research of the Brazilian College of Animal Experimentation (COBEA). Eighteen adult goats with comparable weight (P=0.63) were used, divided into three groups: (1) Traditional group (n=6, weight=26.33 kg ± 2.32 kg, PTB with continuous systolic overload of the RV); (2) Sham or Positive Control group (n=6, weight=26.42 kg±2.63 kg, loose banding, no overload of the RV); and Intermittent group (n=6, weight=25.17 kg ± 2.48 kg, PTB with adjustable device and 12 hours/day of intermittent systolic overload of the RV).

RV systolic overload protocol and pressure readings Traditional Group RV training started during the banding implant surgery. The animals remained under continuous systolic overload of the RV for a period of four weeks, with conventional fixed banding adjusted on the day of the surgery in order to reach an RV systolic pressure of about 70% of systemic systolic pressure, provided that there was no more than a 10% drop in systemic systolic pressure. Pressures of RV, PT, and aorta (Ao) were recorded twice a week with the animal conscious and immobilized on a special stretcher.

Anesthesia The animals were fasted for 24 hours before the surgery and received Xylazine 2%, 0.1 mg/kg IM, as preanesthetic medication. Anesthesia was induced with propofol 1% (7 mg/kg), intravenously (IV) for orotracheal intubation. The animals were maintained under mechanical ventilation

Sham Group As in the Traditional group, hemodynamic measurements

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were taken twice a week during the four weeks of the study and the banding device was kept deflated throughout the protocol.

and septal walls were separated so that cardiac masses could be weighed individually in a METTLER AE-200 (MettlerToledo AG, Greifensee, Switzerland) digital scale.

Intermittent Group The RV training started after approximately 60 hours of convalescence. As in the Traditional group, baseline pressures of RV, PT, and Ao were recorded with the animal conscious and the device completely deflated. Subsequently, the adjustable banding device was insufflated with 0.9% saline in order to reach the same RV systolic overload as the Traditional group. The pressures were then measured once again. The RV systolic overload was maintained for a period of 12 hours, after which arterial pressures were read one more time. After that, the device was deflated and pressures were measured again. The process of insufflating and deflating the device was performed daily for four weeks, with pressures being measured three times a week. On alternate days, the injected volume was the same as the volume calculated on the last day of hemodynamic measurements.

Tissue water content After weighing the cardiac masses, samples were collected from each one for water content assessment. Every sample was initially weighed (IW), then wrapped in aluminum foil and properly identified before being placed in an incubator (temperature: 55-60º C). After about 70 hours of dehydration, every sample was weighed once again to determine dry weight (DW). The percentage of water content was then determined by the following formula, assuming the water distribution was homogenous in the septum and ventricles: WC (%) = 100 – (DW x IW-1 x 100) Analysis of glucose 6-phosphate dehydrogenase (G6PD) maximum activity G6PD maximum activity was determined in the septum and ventricle samples obtained. Samples were stored in liquid nitrogen and homogenized in extraction buffer (proportion 1:5 weight/volume). The material kept in ice was homogenized using Polytron (PT 3100, Kinematica AG, Littau-Lucerne, Switzerland), at maximum speed for 30 seconds. Cell remnants were separated by centrifugation (15,000 g, 15 minutes, 4ºC) using a Centrifuge 5417 C/REppendorf (Hamburg, Germany). Enzymatic activity was analyzed using the supernatant of the last centrifugation. Proteins were quantified using the BCATM protein assay kit (PIERCE Biotechnology, Rockford, IL, USA). Results were expressed as nmol.min-1.mg-1 of protein present in the extract. The extraction buffer for G6PD contained Tris-HCl (50 mM) and EDTA (1 mM), with a pH of 8.0. The assay buffer (270 mL/sample) was comprised of Tris-HCl (8.6 mM), MgCl2 (6.9 mM), NADP+ (0.4 mM), and Triton X-100 0.05% (volume/volume), with a pH of 7.6. The reaction was initiated by adding 15 mL of Glucose-6-phosphate (1.2 mM) to the enzymatic extract (15 mL sample) and it was monitored for 10 minutes at 25º C. Absorbance was monitored at 340 nm, the extinction coefficient being 6.22 for that particular wavelength. The biochemical reaction is based on glucose phosphorylation and subsequent oxidation of glucose-6phosphate to 6-phosphogluconate catalyzed by G6PD. G6PD activity levels were determined indirectly as the total NADPH produced in the pentose phosphate pathway.

Echocardiographic study All animals underwent echocardiographic evaluation by the same observer prior to the protocol and weekly after surgery. During the exams, the goats were sedated with Ketamine (10 mg/kg, intramuscular) and kept in the left lateral decubitus. The ACUSON Cypress (Siemens Healthcare, Mountain View, USA) echocardiography machine was used as well as the multi-frequency sector transducer (1.8-3.6 MHz) to capture images and analyze flow. The thicknesses of the interventricular septum (IVS) and left ventricle (LV) posterior wall were measured by two-dimensional echocardiogram at the end of diastole through longitudinal parasternal section at the mitral valve cusps [13]. The thickness of the RV free wall was obtained through transverse parasternal section (at the great vessels and at the papillary muscles level) and longitudinal four-chamber section in the region where its boundaries were more easily seen. Finally, the arithmetic mean of those values was obtained. Weighing cardiac masses At the end of the protocol, the animals were euthanized for resection of the heart. Anesthesia was deepened and heparin (5 mg/kg) was administered endovenously. Then, potassium chloride was administered until cardiac arrest. At that time, samples of the RV, LV, and interventricular septum were collected, weighed, and immediately placed in tagged plastic containers. The samples were stored in liquid nitrogen (-80ºC) until they could be transferred to the Genetics and Molecular Cardiology Laboratory, where they were kept in a special freezer (Forma Scientific -80º C). The heart was then removed from the thorax. The great vessels, atria, as well as the cardiac valves and epicardial fat were carefully resected. Ventricular

Statistical Analysis Means of the hemodynamic and echocardiographic variables were compared between groups and throughout the protocol by two-way analysis of variance (ANOVA) with repeated measures. Values for mass, water content, and G6PD maximum activity in the RV, LV, and IVS were compared

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by one-way ANOVA. Both analyses were followed by the Bonferroni post hoc test. Systolic overload imposed on the RV, in the Traditional and Intermittent groups, was assessed by calculating the areas under the curve (trapezoidal method). The comparison between those areas was made through unpaired Student’s t-test. Values were expressed as mean ± standard deviation (SD), unless otherwise indicated. The significance level was 5% for all cases. Statistical analyses were done using GraphPad Prism v.4 (San Diego, CA, USA) and SigmaStat v.3.11.0 (Systat Software, Inc., San Jose, CA, USA).

the Intermittent group, starting in the first week of the study when compared to the Sham group (P<0.001), and in the second and fourth weeks of the study when compared to the Traditional group (P<0.01; Figure 2). There was no variation among the groups in the thicknesses of the interventricular septum and the LV posterior wall.

RESULTS Hemodynamics RV/PT pressure gradient The Traditional group showed a decrease in gradient after the second postoperative day (from 45.00 mmHg ± 4.90 mmHg to 39.25 mmHg ± 13.05 mmHg), but remained stable until the end of the protocol (limits: 36.33 mmHg ± 4.04 mmHg to 40.00 mmHg ± 7.72 mmHg). During euthanasia, there was a significant decrease in the RV/PT gradient in the Traditional group (P<0.05), compared to the values of the fourth week. In the Sham group, as opposed to the others, pressure gradient (limits: 4.67 mmHg ± 2.08 mmHg to 9.40 mmHg ± 4.51 mmHg) was maintained throughout the protocol (P<0.05). Peak pressure gradients were significantly higher in the Intermittent group (limits: 46.67 mmHg ± 6.80 mmHg to 59.00 mmHg ± 8.29 mmHg) (P<0.05), alternating with periods of “rest” of the RV. The RV/PT gradient remained elevated in both study groups compared to the Sham group (P<0.001). The Traditional group was subjected to a significantly larger area of systolic overload (23,764 mmHg.h ± 2,192 mmHg.h) than the Intermittent group (17,414 mmHg.h ± 1,144 mmHg.h; P<0.0001). Both Traditional and Intermittent groups had larger areas of systolic overload than the Sham group (3,841 mmHg.h ± 1,298 mmHg.h; P<0.05).

Fig. 1 – Temporal comparison of the RV/Ao maximum ratio in the Traditional, Sham, and Intermittent groups *P<0.05 compared to Baseline instant in its respective group; # P<0.05 difference between the Traditional and Intermittent groups compared to the Sham group; & P<0.05 difference between the Traditional and Intermittent groups.

RV/Ao pressure ratio Baseline RV/Ao pressure ratio of approximately 0.25 was similar in all groups. During surgery, RV/Ao ratio of 0.70 was reached in the stimulated groups. However, after the first week, the ratio decreased significantly in the Traditional group (P<0.05) and remained stable for the remainder of the study. In the Sham group, the baseline RV/Ao ratio remained stable throughout the protocol (P<0.05). In the Intermittent group, the maximum RV/Ao ratio was kept at around 0.7 throughout the study, as opposed to the Traditional group (Figure 1; P<0.05).

Fig. 2 – Percentage variation of the thickness (delta) of the free wall of the right ventricle (RV), measured by echocardiography, in the Traditional, Sham, and Intermittent groups throughout the four weeks of study. *P<0.001 compared to Baseline in the Intermittent group and between the Intermittent and Sham groups.

Echocardiographic findings Thickness of the cardiac walls. There was significant percentage variation in the thickness of the RV free wall in

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Morphological findings Measurement of cardiac mass Table 1 shows the weight of the ventricular chamber masses. The Intermittent and Traditional groups showed an increase in RV mass of 57.0% and 36%, respectively, compared to the Sham group (P<0.05). There was no significant variation in the weight of the IVS (P=0.09) and LV (P=0.30) masses among the groups.

groups. In the Traditional group, maximum activity levels of this enzyme in the RV were 55.2% higher than in the Sham group and 40.7% higher than in the Intermittent group (P=0.05). These data are graphically represented in Figure 3. No significant differences were found between the groups in G6PD maximum activity in the LV (P=0.39) and Septum (P=0.31). DISCUSSION

Water content There was no significant variation in water content of the RV myocardium in the Traditional (79.67% ± 1.25%), Sham (79.16 ± 1.28), and Intermittent (80.61 ± 1.87) groups (P=0.27).

This experimental study set out to compare right ventricular hypertrophy in adult goats subjected to intermittent versus traditional systolic overload, highlighting the energy metabolism in the ventricular retraining of mature myocardium. From a morphological standpoint, differences in hypertrophy in favor of the Traditional group were expected due to the higher exposure of the myocardium to hypertrophic stimuli, quantified by the larger area of systolic overload of the right ventricle.

Glucose 6-phosphate dehydrogenase (G6PD) maximum activity Table 2 shows the mean of absolute values for G6PD maximum activity in the Traditional, Sham, and Intermittent

Table 1. Weight of cardiac masses of the right ventricle (RV), interventricular septum (IVS), and left ventricle (LV), normalized by the weight of the animals in the Traditional, Sham, and Intermittent groups.

RV IVS LV

Traditional N=6 1.08 ± 0.17 * 0.96 ± 0.19 1.52 ± 0.21

Sham N=6 0.79 ± 0.15 0.84 ± 0.20 1.35 ± 0.22

Intermittent N=6 1.24 ± 0.16 # 1.09 ± 0.13 1.47 ± 0.10

Table 2. Maximum activity of the glucose-6-phosphate dehydrogenase (G6PD) enzyme in the Traditional, Sham, and Intermittent groups.

P Value RV LV Septum

<0.05 0.09 0.30

Traditional

Sham

Intermittent

P Value

2.11 ± 0.88 1.85 ± 0.22 0.96 ± 0.28*

1.36 ± 0.14 1.80 ± 0.17 0.86 ± 0.25

1.50 ± 0.24* 1.71 ± 0.16 1.13 ± 0.32*

0.05 0.39 0.31

Values = average ± standard deviation; Measures: nmol/min/mg of protein; * n = 5

Values= average in g/Kg ± standard deviation; * P<0.05 compared to the Sham group; # P<0.001 compared to the Sham group.

Fig. 3. – Maximum activity of the Glucose-6-phosphate Dehydrogenase (G6PD) enzyme in the myocardium of the Traditional, Sham, and Intermittent groups. Measures: nmol/min/mg of protein ± standard error. n= 6

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Even though both ventricular retraining groups were able to promote ventricular hypertrophy of similar magnitude compared to the Sham group, the echocardiographic findings of the Intermittent group showed increased RV free wall thickness. However, the length of time of the hypertrophic process was greater than that found in in young animals submitted to just 96-hour intermittent systolic overload protocol. Likewise, morphological and/or echocardiographic analyses revealed no changes in septal thickness, which also diverges from previous studies in young animals that showed significant increase in the septal mass [10]. Perhaps this deviation can be explained by a more efficient protein production in young as opposed to mature myocardium. All three groups showed no variation in myocardium water content, a sign of cellular edema, suggesting the gain in mass was mainly due to enhanced protein synthesis. Previous studies from our laboratory have demonstrated impaired functional and morphological RV performance of adult goats submitted to Traditional systolic overload under the same protocol. [11,12]. Likewise, there was a concordance of impaired RV function and increased RV G6PD activity of Traditional group after 4-week study period, corroborating the findings of the 96-hour systolic overload in young animals [10]. Increased G6PD activity indicates an exacerbation of the pentose phosphate pathway and it can mean loss of redox balance, with higher production of NADPH and reduced glutathione, as well as development of oxidative stress derived from superoxide anions associated with NADPH oxidase. Under pathological conditions, NADPH is produced by activation of G6PD after stimuli from a range of factors, such as angiotensin II, thrombin, and alpha tumor necrosis factor [14,15]. Cardiomyopathy related to protein aggregation and myocardial lesion would be the final consequence. There is growing evidence that increased G6PD activity is associated with oxidative and reductive stress, with new drugs being developed in order to inhibit its activity [16]. For instance, patients with diabetes mellitus show increased G6PD activity and NADPH levels. This metabolic disorder is associated with endothelial dysfunction due to the inhibition of nitric oxide synthesis [17]. Although the mechanisms through which most of the free radicals are produced in the heart are not completely known, it has been suggested that higher glucose oxidation increases the potential of the mitochondrial membrane thereby augmenting NADPH oxidase activity in the vascular system and, consequently, increasing the production of superoxide anions [18,19]. The latter would act as mediators of diabetic vasculopathy and precursors of myocardial dysfunction related to the disease [20,21]. There is a 10-fold increase in G6PD activity in pacing-induced heart failure compared to normal hearts [22].

This study did not directly assess the production of free radicals associated with NADPH oxidase; however, it can be speculated that the overexpression of G6PD observed in the RV of the Traditional group indicates that the Pentose pathway increases the availability of NADPH, providing the release of free radicals via NADPH oxidase and nitric oxide synthase. Thus, this could lead to myocardial lesion caused by accumulation of superoxide anions and protein aggregation and, subsequently, to ventricular dysfunction should the overload continue. This is corroborated by the fact that functional recovery of hearts with compensated hypertrophy is significantly higher than that of non-hypertrophic hearts when myocardial perfusion is intermittently reestablished, a maneuver which prevents or minimizes the accumulation of glycolytic products and H+ ions. Indeed, reestablishment of this subendocardial coronary flow during the resting periods of the Intermittent group would avoid the accumulation of the products of glycolysis and H+ ions. Besides, fatty acid oxidation is directly stimulated during the reestablishment of subendocardial reperfusion in the resting periods from systolic overload as a result of changes in the enzymes and metabolites responsible for the regulation of fatty acid oxidation. Predominance of fatty acid oxidation during periods of rest of the RV could lead to decreased myocardial glucose uptake. On the other hand, increased efficiency of intermittent systolic overload could be related to the release of hypertrophic stimuli and the cascade of protein synthesis, just as in the Traditional group, yet with decreased myocardial energy expenditure. The mechanisms of the hypertrophic process triggered by molecular cascade are likely to happen under good conditions during the 12hour resting period and ideal oxygen delivery. Therefore, the type of retraining, in terms of level and duration of the systolic overload as well as its impact on the myocardium, must be considered. Even though the increase in G6PD is an unspecified pathway for production of free radicals, this study has found an agreement between previously shown right ventricular dysfunction in the Traditional group and the increase in G6PD activity, a situation where there is inadequate oxygen delivery due to continuous systolic overload, likely high consumption of ATP, and, hence, larger production of free radicals. Limitations of the study There are limitations to implementing the results of this study in human beings. Firstly, metabolism and morphological aspects can differ among species. Secondly, the great arteries were normally related in the animals; hence, the ventricle studied (anatomically right) is not the same as the target population in humans (anatomically left). Finally, it is difficult to make meaningful inferences about a hypertrophic process involving several factors based solely on the activity of a particular enzyme. To this

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end, it would be ideal to also analyze the production of free radicals and/or markers of myocardial lesion since there are several influences at play from other metabolic pathways. This rational suggests that future studies of the production of oxidized glutathione, free radicals, and apoptosis may provide important information to this research line.

2. Mee RB. Severe right ventricular failure after Mustard or Senning operation. Two stage repair: pulmonary artery banding and switch. J Thorac Cardiovasc Surg. 1986;92(3 Pt 1):385-90. 3. Siehl DL, Gordon EE, Kira Y, Chua BHL, Morgan HE. Protein degradation in the hypertrophic heart. In: Glaumann H, Ballard FJ, eds. Lysosomes: their role in protein breakdown. London: Academic; 1987.

CONCLUSION

4. Takahashi Y, Nakano S, Shimazaki Y, Kadoba K, Taniguchi K, Sano T, et al. Echocardiographic comparison of postoperative left ventricular contractile state between one- and two-stage arterial switch operation for simple transposition of the great arteries. Circulation. 1991;84(5 Suppl):III180-6.

This study has shown that ventricular retraining in both groups of adult goats led to right ventricular hypertrophy without myocardial edema. Continuous systolic overload promoted increased G6PD activity in the RV myocardium. This enzymatic hyperactivity may be related to increased production of free radicals caused by greater demand for constant myocardial overload stimulus. Conversely, intermittent systolic overload enabled a more efficient RV hypertrophy, considering the smaller area of systolic overload of the RV and decreased G6PD activity.

5. Van der Vusse GJ, Glatz JF, Stam HC, Reneman RS. Fatty acid homeostasis in the normoxic and ischemic heart. Physiol Rev. 1992;72(4):881-940. 6. Taegtmeyer H. Energy metabolism of the heart: from basic concepts to clinical applications. Curr Probl Cardiol. 1994;19(2):59-113. 7. Grynberg A, Demaison L. Fatty acid oxidation in the heart. J Cardiovasc Pharmacol. 1996;28(Suppl 1):S11-7.

ACKNOWLEDGEMENTS The authors are grateful to SILIMED, Rio de Janeiro, RJ, for the donation of the adjustable banding devices and to FAPESP, for the research grant nº 2006/50831.

8. Huss JM, Kelly DP. Mitochondrial energy metabolism in heart failure: a question of balance. J Clin Invest. 2005;115(3):547-55. 9. Sambandam N, Lopaschuk GD. Brownsey RW, Allard MF. Energy metabolism in the hypertrophied heart. Heart Fail Rev. 2002;7(2):161-73.

Authors’ roles & responsibilities

10. Assad RA, Atik FA, Oliveira FS, Fonseca-Alaniz MH, Abduch MC, Silva GJ, et al. Reversible pulmonary trunk banding. VI: Glucose-6-phosphate dehydrogenase activity in rapid ventricular hypertrophy in young goats. J Thorac Cardiovasc Surg. 2011;142(5):1108-13.

RSA

Design, supervision, and execution of the project; statistical analysis; writing and review of the draft LAM Execution of the project; surgical procedures; data collection; and writing of the draft MHFA Processing of samples and energy metabolism analysis MCDA Echocardiographic exams; writing and review of the draft GJJS Statistical analysis and writing of the draft FSO Assistance in surgical procedures LFPM Supervision; statistical analysis; and review of the draft JEK Design; energy metabolism analysis; supervision; and review of the draft

11. Miana LA, Assad RS, Abduch MC, Gomes GS, Nogueira AR, Oliveira FS, et al. Sobrecarga sistólica intermitente promove melhor desempenho miocárdico em animais adultos. Arq Bras Cardiol. 2010;95(3):364-72. 12. Miana LA, Assad RS, Abduch MC, Silva GJ, Nogueira AR, Aiello VD, et al. Reversible pulmonary trunk banding VIII: Intermittent overload causes harmless hypertrophy in adult goat. Ann Thorac Surg. 2013;95(4):1422-8. 13. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al; Chamber Quantification Writing Group; American Society of Echocardiography’s Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18(12):1440-63.

REFERENCES 1. Cochrane AD, Karl TR, Mee RB. Staged conversion to arterial switch for late failure of the systemic right ventricle. Ann Thorac Surg. 1993;56(4):854-61.

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14. Matsui R, Xu S, Maitland KA, Hayes A, Leopold JA, Handy DE, et al. Glucose-6 phosphate dehydrogenase deficiency decreases the vascular response to angiotensin II. Circulation. 2005;112(2):257-63.

19. Hink U, Li H, Mollnau H, Oelze M, Matheis E, Hartmann M, et al. Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res. 2001;88(2):E14-22. 20. Park J, Rho HK, Kim KH, Choe SS, Lee YS, Kim JB. Overexpression of glucose-6-phosphate dehydrogenase is associated with lipid dysregulation and insulin resistance in obesity. Moll Cell Biol. 2005;25(12):5146-57.

15. Li JM, Mullen AM, Yun S, Wientjes F, Brouns GY, Thrasher AJ, et al. Essential role of the NADPH oxidase subunit p47(phox) in endothelial cell superoxide production in response to phorbol ester and tumor necrosis factor-alpha. Circ Res. 2002;90(2):143-50.

21. Serpillon S, Floyd BC, Gupte RS, George S, Kozicky M, Neito V, et al. Superoxide production by NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglycemic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydrogenase-derived NADPH. Am J Physiol Heart Circ Physiol. 2009;297(1):H153-62.

16. Gupte SA. Glucose-6-phosphate dehydrogenase: a novel therapeutic target in cardiovascular diseases. Curr Opin Investig Drugs. 2008;9(9):993-1000. 17. Guzik TJ, Mussa S, Gastaldi D, Sadowski J, Ratnatunga C, Pillai R, et al. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxidase synthase. Circulation. 2002; 105(14):1656-62.

22. Recchia FA, McConnell PI, Bernstein RD, Vogel TR, Xu X, Hintze TH. Reduced nitric oxide production and altered myocardial metabolism during the decompensation of pacing-induced heart failure in the conscious dog. Circ Res. 1998;83(10):969-79.

18. An D, Rodrigues B. Role of changes in cardiac metabolism in development of diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol. 2006;291(4):H1489-506.

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Nunes JKVRS, et al. - Depression after CABG: a prospective study ORIGINAL ARTICLE

Depression after CABG: a prospective study Depressão após revascularização do miocárdio: um estudo prospectivo

Joana Kátya Veras Rodrigues Sampaio Nunes1, MSc; José Albuquerque de Figueiredo Neto2, PhD; Rosângela Maria Lopes de Sousa1, MSc; Vera Lívia Xavier de Castro Costa3; Flor de Maria Araújo Mendonça Silva1, MSc; Ana Flávia Lima Teles da Hora4; Edna Lúcia Coutinho da Silva1, MSc; Lívia Mariane Castelo Branco Reis1, MSc

DOI: 10.5935/1678-9741.20130080

RBCCV 44205-1502

Abstract Introduction: Depression during or shortly after hospitalization elevated two to three times the risk of mortality or nonfatal cardiac events, significantly increasing the morbidity and mortality of these patients. Objective: To assess the impact of revascularization on symptoms of depression in patients with coronary artery disease. Methods: A prospective cohort study of 57 patients of both sexes undergoing coronary artery bypass grafting between June 2010 and June 2011. We used the SF-36 to assess quality of life, and the Beck Depression Inventory to detect depressive symptoms, applied preoperatively and six months. Results: The prevalence of patients aged 60-69 years was 22 patients (38.60%), 39 men (68.42%), 26 described themselves as mixed race (45.61%), 16 literate (28.07 %) and 30 married

(52.63%). The beck depression inventory score demonstrated increased after revascularization: 15 patients mild (26.32%) at time zero to 17 (29.82%) after. And with moderate, seven patients (12.28%) before and 10 (17.54%) after. In the categories of individuals with decreased minimum degree of 32 (56.14%) to 28 (49.12%), and severe of three (5.26%) for two (3.51%) patients. Association was observed between beck depression inventory, gender, age, lifestyle, comorbidities and quality of life. Conclusion: There was a high prevalence of elevated beck depression inventory scores, lowest scores of depressive symptoms among men and association between the improvement of quality of life scores and beck depression inventory.

Postgraduate Program in Health Sciences, Universidade Federal do Maranhão (UFMA), São Luís, MA, Brazil. 2 Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil. 3 Instituto Nacional de Assistência Médica da Previdência Social (INAMPS), São Luís, MA, Brazil. 4 Universidade Federal do Pará (UFPA), Belém, PA, Brazil.

Work carried out at Universidade Federal do Maranhão (UFMA), São Luís, MA, Brazil.

Descriptors: Myocardial revascularization. Depression. Quality of life.

1

Correspondence address: Joana Kátya Veras Rodrigues Sampaio Universidade Federal do Maranhão Av. dos Portugueses, 1966 – Bacanga – São Luís, MA Brazil – Zip code: 65080-805 E-mail: lylofl@yahoo.com.br Article received on May 29th, 2013 Article accepted on September 10th, 2013

Financial support: FAPEMA (Fundação de Amparo à Pesquisa e Desenvolvimento Científico do Maranhão).

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de Depressão Beck para detectar sintomas depressivos, aplicados no pré-operatório e após seis meses. Resultados: A prevalência de pacientes na faixa etária de 60 a 69 anos foi de 22 (38,60%) pacientes, 39 (68,42%) homens, 26(45,61%) autodeclarados pardos, 16 (28,07%) alfabetizados e 30 (52,63%) casados. O escore Inventário de Depressão Beck demonstrou aumento após a revascularização de 15 (26,32%) pacientes em grau leve no momento zero para 17 (29,82%) após. E com grau moderado, sete (12,28%) pacientes antes e 10 (17,54%) após. Nas categorias de indivíduos com grau mínimo houve redução de 32 (56,14%) para 28 (49,12%) e grave de três (5,26%) para dois (3,51%) pacientes. Observou-se associação entre Inventário de Depressão Beck, sexo, idade, estilo de vida, comorbidades e a qualidade vida. Conclusão: Observou-se elevada prevalência de escores elevados de inventário de depressão Beck, piores escores de sintomas depressivos entre homens e associação entre a melhoria dos escores de qualidade de vida e o Inventário de Depressão Beck.

Abbreviations, acronyms & symbols BDI CABG CAD CVD MR QOL WHO

Beck Depression Inventory Coronary artery bypass grafting Coronary artery disease Cardiovascular disease Myocardial revascularization Quality of life World Health Organization

Resumo Introdução: A depressão durante ou logo após a hospitalização, eleva duas a três vezes o risco de mortalidade ou eventos cardíacos não-fatais, aumentando sensivelmente a morbimortalidade desses pacientes. Objetivo: Avaliar o impacto da revascularização do miocárdio nos sintomas de depressão de pacientes portadores de doença arterial coronariana. Métodos: Estudo de coorte prospectivo de 57 pacientes de ambos os sexos, submetidos à revascularização do miocárdio, entre junho de 2010 e junho de 2011. Foram utilizados os questionários SF-36 para avaliar a qualidade de vida, e o Inventário

Descritores: Revascularização Qualidade de vida.

INTRODUCTION

miocárdica.

Depressão.

have shown improvement in both the physical and mental aspect, as well as the overall health status of patients undergoing this intervention providing them best prognosis [15-19]. Due to the importance of coronary artery disease and depression as a public health problem as well as the paucity of information on the topic in our region, this study assessed the impact of coronary artery bypass grafting on quality of life, as well as the prevalence of depressive symptoms in patients with Coronary Artery Disease, at the President Dutra University Hospital (HUUFMA), a reference hospital of the state of Maranhão, in the city of São Luís, aiming at filling this knowledge gap.

The WHO [1] cites cardiovascular disease (CVD) and depression as the most two debilitating and costly conditions in the health context, and these chronic diseases are among the diseases of greatest impact on quality of life (QOL) of the individual. The projections for 2020 remain CVD as the leading cause of death and disability, and currently developing regions contribute most strongly to the burden of these diseases than developed regions [2]. In Brazil, it is estimated that CVD accounts for over 30% of deaths from the 20 years-old subjects [3,4]. It is well known the association between depression and CVD. Furthermore, it has been given its impact on outcome of patients hospitalized for acute coronary disease, as well as preand postoperative of myocardial revascularization (MR) [5]. The presence of depressive symptoms during or shortly after hospitalization increases by two to three times the risk of mortality or nonfatal cardiac events, significantly increasing the morbidity and mortality of these patients [6-11]. As one of the treatments of CVD, CABG surgery is indicated for patients with angina not controlled with medical therapy and for patients with high-grade obstruction of major arteries, meaning the risk of life [12]. About 60% of CVD patients with multivascular indication for surgery may technically be treated by RM [13]. MRI aims to improve the quality of life of patients, relieving symptoms of angina, restoring physical capacity, and increasing their survival [14]. Thus, CABG surgery is an effective intervention for the treatment of symptoms of CVD, prevention of myocardial infarction and reduction of mortality. Furthermore, several studies

METHODS It was a prospective analytical cohort study, developed at the Presidente Dutra University Hospital in São Luís, Maranhão. The study included patients between 39 and 80 years of age, of both genders, with CVD referred for isolated CABG surgery who agreed to participate by signing the written informed consent form. Patients with depression under antidepressant use during psychotherapy or other psychiatric disorders that impede comprehension and communication during the interview were not included. There are also not included patients with unstable angina that required emergency surgery, those with compromised ventricular function and those who refused to sign the consent form. We consecutively assessed 57 patients between June 2010 and June 2011 who underwent isolated CABG surgery. Two

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patients progressed to death after three months of RM, and were excluded from the analysis. The information was obtained through individual interviews performed preoperatively and by telephone after discharge with six months of MRI follow-up. The instruments used in the research were the Beck Depression Inventory (BDI). Data were collected during visits on weekdays and times (morning, afternoon and evening). The first stage, in preoperative, was composed of an interview to assess the clinical and socio-demographic profile, followed by the application of the Beck Depression Inventory (BDI). In the second stage of postoperative, at the sixth month, BDI was applied by telephone. A unique score for each question on the SF-36 was used to evaluate the results, which were transformed into a scale from zero to one hundred, whose low numerical score (less than 50) reflected poor health perception, while a high numerical score (greater than or equal to 50) showed a good awareness of preserved health [20]. For the assessment of depressive symptoms the nosologic criteria used for the Portuguese version were those from the ICD-10 [21] and diagnosis by [21] DSM-IV. In the 1993 edition, different cut-off points have been suggested to assess the intensity of depressive symptoms in depressed psychiatric diagnoses: 09 degree minimum; 10-16, mild; 17-29, moderate; 30-63, severe [21]. The variables: gender, age in years, self-reported color (white, brown and black), marital status (single, married, stable, separated and widowed), education (illiterate, literate, elementary school, middle school, and higher family income, considered the current minimum wage of R$ 545,00 according to the Ministry of Labour and Employment [22]. It was also investigated the self-reported current or previous practice of smoking and drinking. For preparation of the database we used Office Excel 2010. Data were expressed as frequencies (absolute and relative) for categorical variables and mean and standard deviation for continuous variables. To compare the BDI score before and after, with the population being its own control, we applied the Wilcoxon test for paired samples. To verify the association from the frequency distribution of the categories of BDI score in relation to sociodemographic variables and lifestyle, we applied the ChiSquare test. To verify the relationship between the average of SF-36 compared to the BDI score, ANOVA test was used for parametric variables and Kruskal Wallis test for nonparametric variables, and later was applied post hoc Bonferroni. Variables were diagnosed as normal by the Shapiro Wilk test. We used Stata速 statistical software (version 12). For the interpretation of the statistical results in all tables and tests the level of significance was alpha lower than 0.05. The study was approved by the Research Ethics Committee of the University Hospital of the Federal University

of Maranh達o, in the session of the day 19/02/2010 (No. 005 311/20090), meeting the fundamental and complementary requirements of Resolution 196/96 according the National Council of Health/MH under Opinion No. 112/09 and the CEP Registration No. 237/09. RESULTS This study included the evaluation of 57 patients, of which 22 assessed (38.60%) were aged 60-69 years. There was a predominance of men in the sample, 39 (68.42%), individuals who declared themselves browns, 26 (45.61%), literate, 16 (28.07%) married, 30 (52.63%) and monthly income less than minimum wage, 31 (54.39%) (Table 1). By analyzing the distribution of the BDI in zero-six times (Table 2), it was noted increased six months after revascularization in the frequency of individuals with mild depressive symptoms (score 10 - 16), 15 (26.32%) at time 0 to 17 (29.82%) and moderate depressive symptoms (score 17 to 29), seven (12.28%) before and 10 (17.54%) after. In the categories of individuals with minimal depressive symptoms Table 1. Characterization sample of subjects undergoing CABG at different time points. S達o Lu鱈s - MA, 2013. Sociodemographic variables Sex Male Female Age (years) 40 to 49 50 to 59 60 to 69 70 to 79 Self-reported race Caucasian Brown Black Education Illiterate Literate Fundamental Average Upper Marital status Single Married Stable Widower Separate Income <1 salary 1 to 2 wages 2 to 3 wages 3 to 4 wages Total

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n

%

39 18

68.42 31.58

11 18 22 6

19.30 31.58 38.60 10.53

16 26 15

28.07 45.61 26.32

11 16 14 10 6

19.30 28.07 24.56 17.54 10.53

6 30 12 8 1

10.53 52.63 21.03 14.04 1.75

31 19 3 4 57

54.39 33.33 5.26 7.75 100

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Table 2. Frequencies of distribution of depressive symptoms using the test Wilcoxon in patients undergoing coronary artery bypass grafting at different time points. São Luís - MA, 2013. BDI score

P value

Frequency evaluated according Moments assessment (months) 0 6 32 (56.14) 28 (49.12) 15 (26.32) 17 (29.82) 7 (12.28) 10 (17.54) 3 (5.26) 2 (3.51) 57 (100) 57 (100)

0 to 91 10 to 162 17 to 293 30 to 634 Total

0x6 0.1666

Minimum degree; 2Mild; 3Moderate; 4Severe.

1

Table 3. Association through the Chi-Square between depressive symptoms, gender, age, lifestyle, and comorbidities. São Luís - MA, 2013. Variables Sex Male Female Age (years) 42-52 53-63 64-74 75 to 85 Lifestyle Smoking Alcoholism Comorbidity SH1 DM2 TOTAL

Total n (%)

0-9

10-16

BDI Score 17-29

30-63

39 (68.42) 18 (31.58)

13 (46.43) 15 (53.57)

15 (88.24) 2 (11.76)

10 (100) __

1 (50) 1 (50)

11 (19.29) 18 (31.58) 22 (38.58) 6 (10.55)

5 (17.86) 8 (28.57) 11 (39.29) 4 (14.29)

3 (17.65) 6 (35.29) 7 (41.18) 1 (5.88)

2 (20) 3 (30) 4 (40) 1 (10)

1 (50) 1 (50) __ __

35 (61.40) 30 (52.63)

12 (42.86) 13 (46.43)

13 (76.47) 12 (70.59)

9 (90) 4 (40)

1 (50) 1 (50)

45 (78.94) 27 (47.36) 57.00 (100)

23 (81.14) 12 (42.86) 28 (49.12)

11 (64.71) 8 (47.06) 17 (29.82)

9 (90) 5 (50) 10 (17.54)

2 (100) 2 (100) 2 (3.51)

P value 0.003 0.958

0.026 0.479

1 - Systemic Hypertension; 2 - diabetes mellitus.

(score 0 – 9) and severe (score 30-63) there was reduction, 32 (56 14%) to 28 (49 12%) and three (5.26%) to two (3.51%), respectively (Table 2). Were not found for these associations statistically significant differences (P>0.05). We noted in Table 3 the association between symptoms of depression, gender, age, quality of life, lifestyle and comorbidities. With regard to gender we could verify that women prevailed with a minimal degree of the BDI, 15 (53.57%) and men prevailed in the mild and moderate, 15 (88.24%) and 10 100.00%), respectively. With respect to severe, there was one individual (50.00%) for each gender (P=0.003). The age group 64 – 74 years is more common in minimal BDI degrees, 11 (39.29%), mild, 7 (41.18%) and moderate, 4 (40.00%). For ages ranging from 42 to 52 years old versus 53 to 63 years old prevailed with severe grade one (50.00%) each (P=0.958). Smokers accounted for 12 (42.86%), 13 (76.47%), nine (90.00%) and one (50.00%), respectively of minimum degree, mild, moderate and severe BDI (P=0.026). Drinkers accounted for 13 (46.43%), 12 (70.59%), four (40.00%) and one (50.00%) respectively of the score ranges of minimal, mild, moderate and severe BDI (P=0.026).

Among hypertensive we noted that 23 (81.14%), 11 (64.71%), nine (90.00%) and two (100.00%) comprised, respectively, the minimum degree, mild, moderate and severe depressive symptoms. As diabetics accounted for 12 (42.86%) minimum degree, 8 (47.06%) mild, 5 (50.00%) moderate and 2 (100.00%) severe (P=0.479). In the analysis of the association between the BDI and the quality of life (QOL), it was noted that the score for functional capacity ranged from 7.50±10.60 to 71,78±26,43, with statistical significance between categories of symptoms depression: minimal, moderate and severe (P=0.0001). The physical domain of the SF-36 showed variation of 7.35 ± 24.62 to 24.10 ± 39.95 (P=0.3327), being the minimum degree of depressive symptoms in the category with the lowest score. The pain domain ranged from 42.75±23.78 to 67.64±26.41 in the association between categories of symptoms of minimal and moderate depression (P=0.0258). On health aspect there was variation of 32.50±10.60 to 64.28±19.17 (P=0.0315). The vitality ranged from 27.50±3,53 to 71.14 ± 17.63 with all tracks association between symptoms of depression. The social domain was 25.00 ± 35.35 to 82.50

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Table 4. Analysis of variance (ANOVA) between the BDI score and quality of life of patients undergoing myocardial revascularization. São Luís - MA, 2013. Variables BDI 0 – 91 10 – 162 17 – 293 30 – 634 F P value

M* Sd** M Sd M Sd M Sd

CF

FIS

DOR

SAUD

VITAL

SOC

EMO

MEN

71.78a 26.43 51.76 30.81 32.00a 20.43 7.50a 10.60 8.26 0.0001

24.10 39.95 7.35 24.62 12.50 21.24 __

67.64a 26.41 52.47 20.97 42.75a 23.78 43.5 3.53 3.35 0.0258

64.28 19.17 52.76 16.33 56.50 13.99 32.50 10.60 3.17 0.0315

71.14a 17.63 55.88a 12.02 52.00a 13.78 27.50a 3.53 9.03 0.0001

82.50a 19.44 64.70 21.75 56.25a 28.41 25.00a 35.35 7.24 0.0004

64.58a 43.48 21.56a 38.98 16.66a 32.39 16.66 23.56 6.02 0.0013

67.85 19.61 60.47 11.12 63.40 7.89 32.00 0.00 3.65 0.0131

1.16 0.3327

Equal letters within the same column indicate differences between the means; *Mean; **Standard Deviation; 1Minimum degree; 2Mild; 3Moderate; 4Severe. (CF) Functional Capacity; (FIS) Physical Appearance; (DOR) Pain; (SAUD) General Health; (VITAL) Vitality, (SOCIAL) Social Aspect; (EMO) Emotional Appearance; (MENTAL) Mental Health a

± 19.44, with an association between depressive symptoms of minimum, moderate and severe degrees (P=0.0004). The emotional field of the SF-36 ranged from 16.66±32.39 to 64.58±43.48. But the mental aspect ranged from 32.00±0.00 to 67.85±19.61 (P=0.0131).

and depression has been reported as high prevalence (14.00 to 60.00%) [25]. In a study [23] involving depression as a risk factor for early and late morbidity after revascularization, it was verified preoperatively higher frequency of depressive symptoms (20.70%). In hospital discharge this frequency still increased (23.60%) and three months after discharge the level of depression symptoms reduced to 9.8%. Study [24] also reported lower levels of depressive symptoms in women compared to men after revascularization, as described in Table 3. In another study it was noted [26] higher prevalence of men with BDI scores greater than or equal to 10 (symptoms of mild depression to severe). The use of tobacco differs in other studies [23], and it was found a high prevalence of smokers, 22 (20.00%) in other [27] study was found a largest number of smokers with some level of depressive symptoms (BDI score ≥ 10). The number of diabetic patients in this study was different from those in research [23] with an objective similar to ours, where 19 (32.80%) had comorbidity. Diabetes research in São Paulo (Brazil), showed discrete frequency (less than 11.00%) among individuals with depressive symptoms, and hypertension has reached approximately 50.00% between them. In study [26] performed in the state of São Paulo, Brazil between 2006 and 2008, it was noted an inverse association between depression score and domains: functional, physical, pain, health, vitality, social, emotional and mental health of a score of quality of life after CABG, differing from the findings reported in Table 4. The data refer that after revascularization quality of life tends to be improved and thus depression there seems to be less significant. Thus, the quality of life in health practices reveals the need

DISCUSSION The data in Table 1 reveal similarities with the previously available in the literature for patients undergoing coronary artery bypass grafting, where there is a higher prevalence of males, older and under education and underprivileged [23,24]. However, there was disagreement as to the prevalence of brown found in this study, other author [24] reports higher frequencies of caucasians. This last finding should be considered carefully, since Brazil is the country of extreme racial diversity, since each region may be influenced by a colonizing population. In studies [23] involving depression before and after myocardial revascularization, it was noted outcomes similar to those found in this study, as described in Table 2. The survey showed a reduction in the frequency of individuals with BDI scores representative of minimal symptoms of depression (score 0 – 9) and an increase in the frequencies of any categories of depressive symptoms than or equal to mild (score greater than or equal to 10), 46 (79.30%) vs. 42 (76.40%) and 12 (20.70%) vs. 13 (23.60%), respectively. Moreover, research performed in Cuiabá (MT), Brazil, comparing the quality of life of men and women after coronary artery bypass grafting, noted significant reductions in BDI scores after 180 days of the event, without, however, find statistical significance. In the association between coronary artery disease (CAD)

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to insert new concepts in relation to the illness and treatment, showing that the impact of new treatments and health care should be assessed in the field of influence on the quality of life among the chronic diseases [27]. Thus, we note that the presence of symptoms of depression has been linked as a worsening factor on the quality of life of these patients; initially the best quality of life is suggested as a strong influence for a lower frequency of depression in this postoperative group [28].

5. Alves TCTF, Fraguas R, Wajngarten M. Depressão e infarto agudo do miocárdio. Rev Psiquiatr Clin. 2009;36(Suppl 3):88-92. 6. Blumenthal JA, Lett HS, Babyak MA, White W, Smith PK, Mark DB, et al; NORG Investigators. Depression as a risk factor for mortality after coronary artery bypass surgery. Lancet. 2003;362(9384):604-9. 7. Christmann M, Costa CC, Moussalle LD. Avaliação da qualidade de vida de vida de pacientes cardiopatas internados em hospital público. Rev AMRIGS. 2011;55(3):239-43. 8. Fleck MP. Avaliação de qualidade de vida. In: Fráguas Júnior R, Figueiró JAB, eds. Depressões em medicina interna e em outras condições médicas: depressões secundárias. São Paulo: Atheneu; 2001. p.33-43.

CONCLUSION We observed a high prevalence of depressive symptoms among those assessed. There was a reduction in the prevalence rates of depression symptoms after six months of myocardial revascularization without, however, any statistically significant association. Men seem to have the worst scores of depression (BDI) and there was an association between the improvement of quality of life scores and depressive symptoms. Thus, future studies are needed with longer follow-up after the surgical event. Being relevant reflection on the improvement in quality of life of patients, considering the aspects of clinical variability, comorbidities, and the physical and emotional aspects, seeking to know the patient's perception about interventions, designed as effective and definitive.

9. Horsten M, Mittleman MA, Wamala SP, Schenck-Gustafsson K, Orth-Gomér K. Depressive symptoms and lack of social integration in relation to prognosis of CHD in middle-aged women. The Stockholm Female Coronary Risk Study. Eur Heart J. 2000;21(13):1072-80. 10. Lespérance F, Freasure-Smith N. Depression in patients with cardiac disease: a practical review. J Psychosom. 2000;48(45):379-91. 11. Perez GH, Nicolau JC, Romano BW, Laranjeira R. Depressão e síndromes isquêmicas miocárdicas instáveis: diferenças entre homens e mulheres. Arq Bras Cardiol. 2005;85(5):319-22. 12. Pêgo-Fernandes PM, Gaiotto FA, Guimarães-Fernandes F. Estado atual da cirurgia de revascularização do miocárdio. Rev Med. 2008;87(2):92-8.

Authors' roles & responsibilities JKVRS Authorship and data analysis JAFN Advisor and reviewer RMLS Copyediting VLXCC Literature review and data analysis FMAMS Data collection AFLTH Paper review ELCS Data collection LMCBR Data collection

13. Moreira AELC, Hueb WA, Soares PR, Meneghetti JC, Jorge MCP, Chalela WA, et al. Estudo comparativo entre os efeitos terapêuticos da revascularização cirúrgica do miocárdio e angioplastia coronária em situações isquêmicas equivalentes: análise através da cintilografia do miocárdio com 99mTcSestamibi. Arq Bras Card. 2005;85(2):92-9. 14. Souza DSR, Gomes WJ. O futuro da veia safena como conduto na cirurgia de revascularização miocárdica. Rev Bras Cir Cardiovasc. 2008;23(3):III-VII.

REFERENCES 1. World Health Organization (WHO). Global burden of coronary heart disease. In: Mackay J, Mensah G, eds. Atlas of heart disease and stroke. Geneve: WHO; 2004.

15. Nogueira CRSR. Avaliação comparativa da qualidade de vida em pacientes submetidos à cirurgia de revascularização miocárdica com e sem circulação extracorpórea no período de 12 meses [Tese de Doutorado]. São Paulo: Universidade de São Paulo, Faculdade de Medicina; 2008.

2. Ramires JAF, Chagas ACP. Panorama das doenças cardiovasculares no Brasil. In: Nobre F, Serrano CV, eds. Tratado de cardiologia SOCESP. São Paulo: Manole; 2005. p.7-46.

16. Nogueira IDB, Servantes DM, Nogueira PAMS, Pelcerman A, Salvetti XM, Salles F, et al. Correlação entre qualidade de vida e capacidade funcional na insuficiência cardíaca. Arq Bras Cardiol. 2010;95(2):238-43.

3. Brasil. Ministério da Saúde. DATASUS [Acesso em: 12 jun. 2009]. Disponível em: http://www.datasus.gov.br/datasus/datasus.php 4. Jardim TS, Jardim PC, Araújo WE, Jardim LM, Salgado CM. Fatores de risco cardiovascular em coorte de profissionais da área médica: 15 anos de evolução. Arq Bras Cardiol. 2010;95(3):332-8.

17. Seidl EMF, Zannon CML. Qualidade de vida e saúde: aspectos conceituais e metodológicos. Cad Saúde Pública. 2004;20(2):580-8.

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18. Takiuti ME, Hueb W, Hiscock SB, Nogueira CRSR, Girardi P, Fernandes F, et al. Qualidade de vida após revascularização cirúrgica do miocárdio, angioplastia ou tratamento clínico. Arq Bras Cardiol. 2007;88(5):537-44.

24. Guedes AMA, Nascimento FT, Nasrala Neto E, Nasrala ML. Comparação da qualidade de vida relacionada à saúde entre homens e mulheres após revascularização do miocárdio. Rev Científica Hospital Santa Rosa. 2010;1:39-48.

19. Wong MS, Chair SY. Changes in health-related quality of life following percutaneous coronary intervention: a longitudinal study. Int J Nurs Stud. 2007;44(8):1334-42.

25. Connerney I, Shapiro PA, McLaughlin JS, Bagiella E, Sloan RP. Relation between depression after coronary artery bypass surgery and 12- month outcome: a prospective study. Lancet. 2001;358(9295):1766-71.

20. Carneiro AF, Mathias LAST, Rassi Júnior A, Morais NS, Gozzani JL. Avaliação da ansiedade e depressão no pré-operatório em pacientes submetidos a procedimentos cardíacos invasivos. Rev Bras Anestesiol. 2009;59(4):431-8.

26. Lemos C. Associação entre depressão, ansiedade e qualidade de vida em pacientes que apresentam quadro de pós-infarto do miocárdio [Dissertação de Mestrado]. Porto Alegre: Fundação Universitária de Cardiologia, Instituto de Cardiologia do Rio Grande do Sul; 2006. 79p.

21. Cunha JA. Manual da versão em português das escalas Beck. São Paulo: Casa do Psicólogo; 2001.

27. Paim JS, Almeida Filho NA. A crise da saúde pública e a utopia da saúde coletiva. Salvador: Casa da Qualidade; 2000.

22. Brasil. Ministério do Trabalho e Emprego. Salário mínimo. 2010 [Acesso em: 20 maio 2010]. Disponível em: http://www.portal. mte.gov.br/sal_min

28. Gois CFL. Qualidade de vida relacionada à saúde, depressão e senso de coerência de pacientes, antes e seis meses após revascularização do miocárdio [Tese de Doutorado]. Ribeirão Preto: Programa de Pós-Graduação da Escola de Enfermagem de Ribeirão Preto da Universidade de São Paulo. Ribeirão Preto; 2009. 94p.

23. Pinton FA, Carvalho CF, Miyazaki MCOS, Godoy MF. Depressão como fator de risco de morbidade imediata e tardia pós-revascularização cirúrgica do miocárdio. Rev Bras Cir Cardiovasc. 2006;21(1):68-74.

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Koç ZP, et al. ORIGINAL - Twenty four ARTICLE hour imaging delay improves viability detection by Tl-201 myocardial perfusion scintigraphy

Twenty four hour imaging delay improves viability detection by Tl-201 myocardial perfusion scintigraphy Atraso de imagem de 24 horas melhora a viabilidade de detecção por cintilografia de perfusão miocárdica Tl-201

Zehra Pınar Koç1; Tansel Ansal Balcı1; Necati Dağlı1

DOI: 10.5935/1678-9741.20130081

RBCCV 44205-1503

Abstract Objective: Since twenty-four-hour imaging by Tl-201 myocardial perfusion scintigraphy has been introduced as an effective additional procedure, the aim of this study was to compare this method’s result with only rest redistribution procedure in the diagnosis of myocardial viability. Methods: Thirty patients (Seven female, 23 male; mean: 59.8 ± 10.7, 55.8-63.8 years old) with diagnosis of coronary artery disease were involved in this study. All patients had anamnesis of previous myocardial infarction and/or total occlusion of any main artery in the coronary angiography. Myocardial perfusion scintigraphy with Tl-201 with rest four hour (early) redistribution and 24 hour delayed redistribution protocol were performed to all of the patients. The images were evaluated according to 17 segment basis by an experienced nuclear medicine physician and improvement of a segment by visual interpretation was considered as viable myocardial tissue. Results: Viability was found at 52 segments in the early redistribution images and additional 18 segments in the 24 hour delayed redistribution images on segment basis in the evaluation of 510 segments of 30 patients. On per patient basis, among

the 26 patients who had viable tissue, 14 (54%) had additional improvement in 24 hour delayed images. Three (12%) patients had viable tissue in only 24 hour delayed images. Conclusion: Delayed imaging in Tl-201 MPS is a necessary application for the evaluation of viable tissue according to considerable number of patients with additional improvement in 24 hour images in our study, which is restricted to the patients with myocardial infarct.

Fırat University Hospital, Elazig, Turkey.

Correspondence address: Zehra Pınar Koç University Hospital Nuclear Medicine Dpt. – B3 – Elazig, Turkey Zip code: 23119 E-mail: zehrapinarkoc@gmail.com Article received on March 11th, 2013 Article accepted on August 20th, 2013

1

Descriptors: Vascular diseases. Coronary artery bypass. Coronary artery disease. Resumo Objetivo: Dado que a cintilografia Tl -201 24 horas de imagens por perfusão miocárdica foi introduzida como um procedimento adicional efetivo, assim, o objetivo deste estudo foi comparar os resultados deste método com o procedimento único de redistribuição no diagnóstico de viabilidade miocárdica. Métodos: Trinta pacientes (Sete mulheres, 23 homens, média: 59,8 ± 10,7, 55,8-63,8 anos) com diagnóstico de doença arte-

Work carried out at Fırat University Hospital, Elazig, Turkey.

No financial support.

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segmento por interpretação visual foi considerado como tecido miocárdico viável. Resultados: A viabilidade foi encontrada em 52 segmentos de redistribuição das imagens iniciais e 18 segmentos adicionais nas imagens de redistribuição tardias de 24 horas baseadas em segmento, na avaliação de 510 segmentos de 30 pacientes. Em termos de pacientes, entre os 26 pacientes que tinham tecido viável, 14 (54%) apresentaram melhora adicional em imagens tardias de 24 horas. Três (12%) pacientes tiveram tecido viável apenas em imagens tardias de 24 horas. Conclusão: A imagem tardia em TL- 201 MPS é uma aplicação necessária para a avaliação do tecido viável de acordo com o número considerável de pacientes com melhora adicional em imagens de 24 horas em nosso estudo, o qual é restrito aos pacientes com infarto do miocárdio.

Abbreviations, acronyms & symbols ATP CABG CAD C-MRI MPS MR SPECT

Adenosine triphosphate Coronary artery bypass graft surgery Coronary artery disease Cardiac applications of magnetic resonance imaging Myocardial perfusion scintigraphy Magnetic resonance Single photon emission computed tomography

rial coronariana foram avaliados neste estudo. Todos os pacientes tinham anamnese de infarto do miocárdio e/ou oclusão total de uma artéria principal na cinecoronariografia. Cintilografia de perfusão miocárdica com protocolo de Tl-201 em repouso, redistribuição quatro horas (início) e redistribuição tardia 24 horas foi realizada em todos os pacientes. As imagens foram avaliadas de acordo com a base de 17 segmentos por um médico com experiência em medicina nuclear e melhoria de um

Descritores: Doenças vasculares. Ponte de artéria coronária. Doença da artéria coronariana.

INTRODUCTION

dial infarction. Additionally, all the patients had segmental or global wall motion abnormalities and left ventricular impairment (mean ejection fraction: 30.9±8.9) according to the echocardiography results. Patient characteristics are summarized in the Table 1. All the patients’ informed consent forms were obtained prior to the study and after explaining the procedure and the research. Ethics committee approval was not deemed necessary since the study was performed retrospectively.

Myocardial infarction is a critical event and the most common cause of death all over the world. After myocardial infarction, another critical course begins which includes the decision of both presence and extent of the viable myocardial tissue. Since myocardial tissue sometimes preserves its viability by some adaptation methods during infarct, it is possible to observe viable tissue in patients who experienced myocardial infarction. The ‘hibernating’ myocardial tissue is a tissue with impaired flow and function, but with preserved viability. This state of the myocardial tissue can be seen especially by means of radionuclide imaging methods like Tl-201 and F-18 FDG PET/CT. Recently, new methods have been introduced to the field of imaging of the myocardial viability, such as cardiac applications of magnetic resonance imaging (C-MRI) or stress echocardiography [1]. However diagnostic power of the viability assessment by Tl-201 is underestimated because most of the recent comparative studies with Tl201 imaging involve rest redistribution protocol [2]. The aim of this study was to investigate diagnostic importance of 24 hour delayed Tl-201 imaging in our series.

Table 1. Patient characteristics. Age Gender Angina Smoking Diabetes mellitus Hypertension Family history Hyperlipidemia Previous CABG

No of patients 56-64 years 7 female/23 male 19 16 8 14 5 9 3

CABG: Coronary artery bypass graft surgery

Myocardial perfusion scintigraphy Tl-201 myocardial perfusion scintigraphy (MPS) with rest redistribution and delayed redistribution protocol were performed in all patients with the same imaging and acquisition protocols (same timing, filter, gated acquisition, reconstruction parameters (filtered back projection), attenuation and scatter correction). After a fasting period of at least four hours approximately 2 mCi (74 Mbq) Tl-201 (the dose was limited to 2 mCi in case reinjection was required, which did not happen in this approach) was injected via venous line into

METHODS Patients Thirty patients (seven female, 23 male; mean: 59.8±10.7, 55.8-63.8 years old) with diagnosis of coronary artery disease were included in this study. Diagnosis of myocardial infarct was based on anamnesis, electrocardiography results and/or coronary angiography results showing 100% narrowing of any main coronary artery. Sixteen patients underwent additional coronary angiography. All patients had documented myocar-

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the patients. Rest images were obtained at five-ten minutes, early redistribution images at 3-4 hours and late redistribution images at 24 hours after the injection. Single photon emission computed tomography (SPECT) imaging was performed by a dual-head gamma camera equipped with low energy all purpose collimator (GE, Infina). The images were acquired over a 180° arc in 64 projections, each lasting 30 seconds (in case of insufficient quality of images by visual analysis, the imaging time was increased to 40 sec/per frame), in a 64x64 matrix and gated protocol. The butterworth filter with cutoff frequency of 0.5 and order of 10 was applied for the reconstruction of the images.

rest-redistribution and delayed redistribution images, a significant difference between % scores of the segments (P<0.05) or improvement of 0-4 scores by at least one degree was accepted as a threshold. On per patient basis, among the 26 patients who had viable tissue, 14 (54%) had additional improvement on delayed images. Three (12%) patients had viable tissue only on delayed imaging (Figure 1). Additionally all the patients had global or segmental wall motion abnormalities and mean ejection fraction value obtained from rest redistribution images was 30.9 ± 8.9 according to Gated acquisition.

Image interpretation The images were evaluated in short axis, vertical and horizontal long axe slices, and in bull’s eye imaging. This was done according to 17 segment basis by two independent experienced nuclear medicine physicians and improvement of any segment by visual interpretation (greater than 50% uptake increase) was considered as viable myocardial tissue. The analysis of scores (0-4 scores and % scores) was performed by the same physicians. Statistical analysis The comparison of the scores was done by paired samples T test and P<0.05 was considered statistically significant. SPSS 15.0 was used for the analysis. RESULTS In the evaluation of 510 segments of 30 patients, 52 segments in early redistribution images and other 18 segments in delayed redistribution images were considered viable on a segment basis. In order to consider the improvement between the

Fig. 1 - Short axis, vertical axis, horizontal axis, and bulls eye Tl201 MPS images of a patient who has viable tissue only in 24 hour images in septum and anteroseptal wall

Table 2. Myocardial perfusion scintigraphy results of patients who have angiography results. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Angiography Redistribution LAD 100% LAD 80%, Cx 90% Septum LAD-LIMA 100% Anteroseptal, inferior mid apical LAD 95%, Cx 100% Anterior mid LAD 100% LAD 100%, Cx 50%, RCA 95% Anterior mid LAD 95% Septum LAD 100%, RCA 90% Apex LAD 98%, Cx90%, RCA 95% LAD 100% LAD 70%, Cx 100%, RCA 70% Septum RCA 80% Inferior Cx %90 Inferior LAD 100%, Cx 95%, RCA 100% Septum, anteroseptal, inferoseptal LAD 100%, Cx 40%, RCA 100% Anterior mid apical LAD 100%, Cx 70%, RCA 100% Anteroseptal mid

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Delayed Imaging Inferior, septum Anterior mid Lateral basal Anterior apical Apex Septum Anteroseptal mid Inferior apical Inferolateral Septum, anteroseptal mid Apex Anteroseptal basal

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The improved segments at rest redistribution and delayed imaging of patients who underwent angiography are summarized in Table 2. Unfortunately, all the patients were out of follow up after the establishment of the viability. There was no information regarding further management of the patients, whether or not they underwent coronary artery bypass graft surgery (CABG), and what their results were.

creased dose of 24 hour images. However the image quality of our study at 24 hours was in fact comparable to the early redistribution images even close to Tc-99m MIBI images, according to visual interpretation and target non target ratio (2.03; 2.16 and 3.03, respectively). We just preferred to increase the time frame (40 sec versus 30 sec per frame), if necessary. The patient based analysis of the viability assessment in our study revealed that an important percentage of patients (54%) had additional viable tissue in 24 hour images. Since the patients who were included in this study all had fixed defects on rest Tl-201 imaging, this finding is of great importance. The most important result of this study is patients who had improvement only in 24 hour imaging (three patients, 12%), which was not observed in any previous study. However, due to the small sample size the ratio of these patients should be evaluated in a larger study population. In future studies this percentage might increase. The cardiac Tc-99m labeled tracers have superior image quality compared to Tl-201. That is why there are new approaches with Tc-99m compounds employed in the viability assessments. Maurea et al. [14] have shown that administering nitrate during Tc-99m MIBI imaging might demonstrate viable tissue in patients with chronic heart failure. A recent comparative study using this method and the Tl-201 reinjection approach has demonstrated comparable results and good agreement between the two methods [15]. Another recent approach with Tc-99m compounds has included Tc-99m labeled HL91, which is introduced as an alternative application for the viability assessment. Viability was defined as reduced Tc-99m MIBI uptake and increased Tc-99m HL91 uptake; a ‘mismatch’ pattern, especially in the three hour images, which showed high diagnostic accuracy [16]. The most important advance in the field of viability imaging was F-18 FDG PET/CT. Viability assessment by means of F-18 FDG PET has shown significant superiority over 24 hour Tl-201 imaging [17]. F-18 FDG PET has been considered as the gold standard imaging method for detection of myocardial viability [18]. Additionally, according to previous studies, F-18 FDG PET has been able to provide prognostic information [3,19]. Stress echocardiography is another modality which shows viable tissue in the myocardium. According to a meta-analysis sensitivity, specificity, and positive and negative predictive values of dobutamin stress echocardiography were found to be 81%, 80%, 77%, and 85%, respectively [20]. The same researchers have mentioned that radionuclide methods have higher sensitivity and stress echocardiography has higher specificity. Cardiac magnetic resonance (MR) imaging for assessment of the myocardial viability is a new method which can clearly identify cardiac tissue in all the myocardial layers with superior spatial resolution compared to the radionuclide

DISCUSSION Since mortality associated with the heart failure is significantly high, it is important to perform revascularization in patients who might benefit from this procedure. According to a meta-analysis study, revascularization procedures have provided improvements in 79.6% of patients with viable tissue [3]. Viability assessment have gained importance ever since risk factors associated with CABG operations, especially in elderly patients, have become known [4,5]. Viability assessment by means of radionuclide imaging methods is generally effective because these methods provide functional assessment of the myocardial tissue. Tl-201 is a potassium analog and enters myocytes via an active transport mechanism involving the Na+/K+ adenosine triphosphate (ATP) transport system. When Tl-201 enters intracellular space, it goes back to the systemic circulation through diffusion [6]. This kinetic redistribution, which is specific to this agent, allows viability assessment by Tl-201 imaging. The tracer is taken by hibernating myocardium and it can be seen at three hours after injection of radiopharmaceutical. Since Pohost et al. [7] firstl introduced Tl-201 as a viability agent further studies have shown that 24 hour imaging provides important prognostic data [8,9]. Perrone-Filardi et al. [10] observed improvement in approximately 20% of segments in late images, especially in mild to moderately persistent defects. Rest redistribution imaging at three hours is not a sufficient approach as documented in a series which showed 75% of the viability were reported as scars, according to rest-redistribution only Tl-201 imaging [11]. Dilsizian et al. [12] were the first to report the ‘reinjection technique’, which includes a lower dose (1 mCi/37 MBq) Tl-201 injection at three hours and then reimaging. However, 24 hour imaging with Tl-201 still preserves its diagnostic significance as documented in a recent study [13]. In this comparative study with echocardiography follow up, researchers observed 20% more segments with viability in the 24 hour images that had not improved in rest redistribution imaging. We found 26% (18 out of 70 viable segments) additional segments with improvement in the 24 hour images. Although previous researchers performed 24 hour imaging with a higher Tl-201 dose (3-4 mCi/111-148 mBq) we did not increase the dose. The justification for increasing the dose of radiopharmaceutical is the poor image quality of Tl-201 especially in de-

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methods. An analysis of viability assessment by cardiac MR has concluded that MR is an excellent tool to demonstrate viability [21]. A comparative study with cardiac MR and Tl201 imaging has documented that MR has higher specificity, negative predictive value and overall accuracy; however, in that study the Tl-201 imaging was performed in a rest redistribution manner [2]. Cardiac MR has had comparable diagnostic accuracy with PET according to a previous study [22]. One of the important characteristics of our study is the homogeneity of our study population, which consists only of patients with documented myocardial infarction. In other studies about viability assessment there have been patient populations with angiographically significant coronary artery disease (CAD), or patients with left ventricular impairment with myocardial infarction in some (50%) of the patients [23,24]. In those studies, significant percentages of the segments were already nonviable (144/398 and 56/240, respectively). However, the primary pathology of our patients was CAD with known myocardial infarct tissues thus our study includes subjects with periinfarct viable tissue. Another study about viability assessment by both rest redistribution Tl-201 and contractile reserve assessment by low-dose dobutamine protocol included 41 patients, 39 of whom had documented myocardial infarction, and found the protocol easy and feasible [25]. Although their analysis did not include additional late Tl-201 imaging, their study group was similar to ours and a smaller percentage of the segments in their analysis was nonviable (33/890), as in our study. This specially enabled our study to evaluate more segments regarding viability. Limitations of this study were its retrospective structure and lack of all the patients’ angiography or follow up results. Quantification of the data also couldn’t be performed because of a technical problem associated with our analysis program.

1. Arrighi JA, Dilsizian V. Multimodality imaging for assessment of myocardial viability: nuclear, echocardiography, MR, and CT. Curr Cardiol Rep. 2012;14(2):234-43. 2. Regenfus M, Schlundt C, von Erffa J, Schmidt M, Reulbach U, Kuwert T, et al. Head -to-head comparison of contrast-enhanced cardiovascular magnetic resonance and 201Thallium single photon emission computed tomography for prediction of reversible left ventricular dysfunction in chronic ischaemic heart disease. Int J Cardiovasc Imaging. 2012;28(6):1427-34. 3. Aikawa P, Cintra AR, Leite CA, Marques RH, Silva CT, Afonso MS, et al. Impact of coronary artery bypass grafting in elderly patients. Rev Bras Cir Cardiovasc. 2013;28(1):22-8. 4. Sá MP, Nogueira JR, Ferraz PE, Figueiredo OJ, Cavalcante WC, Cavalcante TC, et al. Risk factors for low cardiac output syndrome after coronary artery bypass grafting surgery. Rev Bras Cir Cardiovasc. 2012;27(2):217-23. 5. Allman KC, Shaw LJ, Hachamovitch R, Udelson JE. Myocardial viability testing and impact of revascularization on prognosis in patients with coronary artery disease and left ventricular dysfunction: a meta-analysis. J Am Coll Cardiol. 2002;39(7):1151-8. 6. Demirkol MO. Myocardial viability testing in patients with severe left ventricular dysfunction by SPECT and PET. Anadolu Kardiyol Derg. 2008;8(Suppl 2):60-70. 7. Pohost GM, Zir LM, Moore RH, McKusick KA, Guiney TE, Beller GA. Differentiation of transiently ischemic from infarcted myocardium by serial imaging after a single dose of thallium-201. Circulation. 1977;55(2):294-302. 8. Gutman J, Berman DS, Freeman M, Rozanski A, Maddahi J, Waxman A, et al. Time to completed redistribution of thallium-201 in exercise myocardial scintigraphy: relationship to the degree of coronary artery stenosis. Am Heart J. 1983;106(5 Pt 1):989-95.

CONCLUSION According to our results the 24 hour Tl-201 imaging is a necessary application for the identification of viable myocardial tissue. Considering the large number of patients who benefit from this additive method, this study can encourage future comparative studies with 24 hour imaging protocol and new diagnostic applications in this area.

9. Kiat H, Berman DS, Maddahi J, De Yang L, Van Train K, Rozanski A, et al. Late reversibility of tomographic myocardial thallium-201 defects: an accurate marker of myocardial viability. J Am Coll Cardiol. 1988;12(6):1456-63.

There is no conflict of interest.

10. Perrone-Filardi P, Pace L, Prastaro M, Squame F, Betocchi S, Soricelli A, et al. Assessment of myocardial viability in patients with chronic coronary artery disease. Rest-4-hour-24-hour 201Tl tomography versus dobutamine echocardiography. Circulation. 1996;94(11):2712-9.

Authors’ roles & responsibilities ZPK TAB ND

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23. Wu YW, Huang PJ, Lee CM, Ho YL, Lin LC, Wang TD, et al. Assessment of myocardial viability using F-18 fluorodeoxyglucose/Tc-99m sestamibi dual-isotope simultaneous acquisition SPECT: comparison with Tl-201 stress-reinjection SPECT. J Nucl Cardiol. 2005;12(4):451-9.

17. Brunken RC, Mody FV, Hawkins RA, Nienaber C, Phelps ME, Schelbert HR. Positron emission tomography detects metabolic viability in myocardium with persistent 24-hour single-photon emission computed tomography 201Tl defects. Circulation. 1992;86(5):1357-69.

24. Gutberlet M, Fröhlich M, Mehl S, Amthauer H, Hausmann H, Meyer R, et al. Myocardial viability assessment in patients with highly impaired left ventricular function: comparison of delayed enhancement, dobutamine stress MRI, end-diastolic wall thickness, and TI201-SPECT with functional recovery after revascularization. Eur Radiol. 2005;15(5):872-80.

18. Ammirati E, Rimoldi OE, Camici PG. Is there evidence supporting coronary revascularization in patients with left ventricular systolic dysfunction? Circ J. 2011;75(1):3-10.

25. Heiba SI, Yee G, Abdel-Dayem HM, Youssef I, Coppola J. Combined rest redistribution thallium-201 SPECT and low-dose dobutamine contractility assessment in a simple and practical new viability protocol. Ann Nucl Med. 2009;23(2):197-203.

19. Rohatgi R, Epstein S, Henriquez J, Ababneh AA, Hickey KT, Pinsky D, et al. Utility of positron emission tomography in

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Braulio R, et al. - IndicatorsARTICLE of surgical treatment of patent ductus arteriosus ORIGINAL in preterm neonates in the first week of life

Indicators of surgical treatment of patent ductus arteriosus in preterm neonates in the first week of life Indicadores para o tratamento cirúrgico na persistência do ducto arterial em neonatos prematuros na primeira semana de vida

Renato Braulio1, MD, MSc; Cláudio Léo Gelape1, MD, PhD; Fátima Derlene da Rocha Araújo2, MD, MSc; Kelly Nascimento Brandão2, MD; Luciana Drummond Guimarães Abreu2, MD; Paulo Henrique Nogueira Costa1, MD, MSc; Flávio Diniz Capanema1, MD, PhD

DOI: 10.5935/1678-9741.20130082

RBCCV 44205-1504

Abstract Objective: To identify clinical and echocardiographic indicators of the necessity for early surgical closure of patent ductus arteriosus in preterm neonates. Methods: The prospective study was performed at the Neonatal Unit of Hospital Municipal Odilon Behrens between 2006 and 2010. The study population comprised 115 preterm neonates diagnosed with patent ductus arteriosus in the first week after birth, of whom 55 (group S) were submitted to clinical and or surgical closure and 60 (group NS) received nonsurgical treatment. The parameters assessed were birth weight, diameter of the ductus arteriosus (DAD), left atrial-to-aortic root diameter ratio (LA:Ao), the quotient of DAD2 and birth weight (mm2/kg), and ductal shunting. Results: The study population comprised 58 males and 57 females. The average birth weight of group S (924.0 ± 224.3 g) was significantly (P=0.049) lower than that of group NS (1012.3 ± 242.8 g). The probability of the preterm neonates being submitted to surgical closure was 62.1% (P=0.006) when the DAD2/birth weight index was > 5 mm2/kg, 72.2% (P=0.001)

when the LA:Ao ratio was > 1.5, and 61.2% when ductal shunting was high (P=0.025). Conclusion: The parameters DAD2/birth weight index > 5 mm2/kg, LA:Ao ratio > 1.5 and high ductal shunting were statistically significant indicators (P<0.05) of the need for surgical closure of patent ductus arteriosus in low birth weight preterm neonates. Moreover, when an LA:Ao ratio > 1.5 was associated with the occurrence of shock, the probability of surgical closure increased to 78.4%.

Federal University of Minas Gerais, School of Mediciney, Belo Horizonte, MG, Brazil. 2 Hospital Municipal Odilon Behrens, Department of Pediatrics, Belo Horizonte, Minas Gerais, Brazil.

Correspondence address: Renato Braulio Hospital das Clínicas da UFMG Av. Prof. Alfredo Balena, 110 – 5º andar – Santa Efigênia – Belo Horizonte, MG, Brazil – Zip code: 30130-100 E-mail: renatobraulio1@ig.com.br

Descriptors: Ductus arteriosus, patent. Echocardiography. Infant, premature, diseases. Resumo Objetivo: Identificar parâmetros clínicos e ecocardiográficos para a indicação do tratamento cirúrgico precoce da persistência do ducto arterial. Métodos: Esse estudo prospectivo foi conduzido na Unidade Neonatal do Hospital Municipal Odilon Behrens entre 2006

1

Work carried out at Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG), Belo Horizonte, MG, Brazil and Hospital Municipal Odilon Behrens (HOB), Belo Horizonte, MG, Brazil.

Article received on August 1st, 2013 Article accepted on October 8th, 2013

No financial support.

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Resultados: O estudo abrangeu 58 pacientes do sexo masculino e 57 do feminino. O peso médio ao nascer do grupo S (924,0 ± 224,3 g) foi significativamente (P=0,049) menor do que do grupo NS (1012,3 ± 242,8 g). A probabilidade dos neonatos prematuros serem submetidos à cirurgia foi 62.1% (P=0,006) quando o índice DAD2/peso ao nascer era > 5 mm2/kg, 72,2% (P=0,001) quando a razão LA:Ao era > 1,5 e 61,2% (P=0,025) quando o fluxo no ducto era alto. Conclusão: Os parâmetros DAD2/peso ao nascer > 5 mm2/ kg, razão LA:Ao > 1,5 e alto fluxo no ducto foram preditores estatisticamente significativos (P<0,05) da necessidade de fechamento cirúrgico do persistência do ducto arterial em neonatos prematuros com baixo peso ao nascer. Adicionalmente, quando a razão LA:Ao > 1,5 estava associada ao choque, a probabilidade de tratamento cirúrgico aumentou para 78,4%.

Abbreviations, acronyms & symbols DA DAD LA:Ao PDA ROC

Ductus arteriosus Diameter of the ductus arteriosus Left atrial-to-aortic root diameter ratio Patent ductus arteriosus Receiver operating characteristic

e 2010. A população estudada compreendeu 115 neonatos prematuros diagnosticados com persistência do ducto arterial na primeira semana após o nascimento, dos quais 55 (grupo S) foram submetidos ao tratamento clínico e ou cirúrgico e 60 (grupo NS) ao tratamento clínico. Os parâmetros analisados foram peso ao nascer, diâmetro do ducto arterial (DAD), relação diâmetro do átrio esquerdo pelo diãmetro da aorta (AE/Ao), índice DAD2/peso ao nascer e fluxo no ducto.

Descritores: Permeabilidade do Ecocardiografia. Doenças do prematuro.

INTRODUCTION

canal

arterial.

precordium [7-9]. Considering that early surgical intervention can reduce morbidity and mortality among preterm neonates, it is of the utmost importance to recognize the signs and symptoms that support a surgical approach. Within this context, the aim of the present study was to identify the clinical and echocardiographic parameters that indicate the need for early surgical closure of PDA in preterm neonates who have been found unresponsive to, or unsuitable to receive, appropriate medication.

Patent ductus arteriosus (PDA) is a congenital heart problem that affects some neonates in which the ductus arteriosus, the blood vessel connecting the descending aorta and the pulmonary artery, fails to close after birth. Although the disorder can affect full-term infants, it is significantly more prevalent in preterm babies. The PDA in preterm neonates has been associated with increased morbidity and mortality if left uncorrected [1-3]. PDA correction in preterm neonates can be achieved via surgical methods (open surgery, videolaparoscopy or endovascular approaches) or clinical therapy via [4-6]. The treatment of choice is the administration of nonsteroidal antiinflammatory drugs (such as indomethacin and ibuprofen) that inhibit the prostaglandins known to keep the ductus arteriosus (DA) open [1]. In cases where clinical treatment fails, the DA can be closed by surgical ligation. However, while early closure of the DA improves the long-term cardiorespiratory functions of infants [2], the ideal time of application of the surgical procedure in preterm neonates remains somewhat controversial [3]. Although premature surgical closure of DA has received considerable attention in recent years, no definitive criteria of indication of this procedure have been established. The surgical indications most frequently applied appear to be related to the presence of heart anomalies (increased DA diameter and enlarged left atrium) and clinical signs such as shock, high parasternal systolic murmur and hyperdynamic

METHODS Details of the project were submitted and approved by the Ethical Research Committee of the Hospital Municipal Odilon Behrens (CAAE 0012.0.216.000-06; FR99402; protocol no. 82/2006). The aims and objectives of the study were explained to the parents or legal guardians of the infants, and written informed consent was obtained prior to the commencement of the study. All procedures were performed according to the ethical principles of research as embodied in the Declaration of Helsinki. The prospective study was performed at the Neonatal Unit of the Hospital Municipal Odilon Behrens between 2006 and 2010. Clinical and echocardiographic data of 215 preterm neonates (gestational age ≤ 30 weeks) were assessed and those diagnosed with PDA, according to the echocardiogram acquired on the 3rd or 4th day after birth, were selected for possible inclusion in the study. Neonates presenting congenital cardiovascular pathologies other than

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PDA (as determined by echocardiography using a Toshiba Nemio 30 ultrasound instrument) and infants who died during the first week after birth were excluded from the study. The final study population comprised 115 infants, all of whom received clinical treatment except for those who presented contraindications for ibuprofen therapy or PDA-induced shock. Sixty of the infants responded to the non-surgical treatment (group NS), while 55 were submitted to surgery for the correction of PDA (group S). The treatment with ibuprofen consisted of intravenous perfusion of three doses at 24 h intervals: 1st dose 10 mg/kg, 2nd and 3rd doses 5 mg/kg. The surgical technique applied to the S group involved left posterior thoracotomy in the third or fourth intercostal space via the triangle of auscultation, followed by extra pleural dissection of the DA and ligation with titanium clips under general anaesthesia [9,10]. The data assessed for all patients included birth weight, gestational age, clinical and echocardiographic signs of PDA in the first week after birth, treatment received to correct the defect (surgical or non-surgical), diameter of the DA (DAD), left atrial-to-aortic root diameter ratio (LA:Ao), the quotient of DAD2 and birth weight (mm2/kg), and ductal shunting. Shunting was assessed on the parasternal short axis by color Doppler from the pattern and magnitude of shunt of the arterial canal in the direction of the pulmonary artery, and classified as: low (flow from the pulmonary branch up to the distal portion of the pulmonary artery), moderate (flow up to the mid-third of the pulmonary artery), and high (flow up to the proximal portion of the pulmonary artery and reaching the pulmonary valve). The diameter of the arterial canal was measured by two-dimensional echocardiography at the level of the pulmonary vein ostium. Univariate analyzes of the clinical and echocardiographic data and their association with surgical closure were established using χ2 and Student t tests. Multivariate logistic regression analysis was performed in order to assess cross influences between the variables. Results were considered statistically significant at 5% probability (P<0.05). A receiver operating characteristic (ROC) curve was constructed for each of the variables in order to determine those that

constituted good predictors for the outcome of interest (surgical indication). According to the ROC curves, the cut off points for the DAD2/birth weight index was 5 mm2/kg and that for the LA:Ao ratio was 1.5. RESULTS Of the 215 preterm neonates initially screened, 115 (53.5%) were diagnosed with PDA by echocardiography and included in the study. While the numbers of males (58/115; 50.4%) and females (57/115; 49.6%) in the study population were similar, the percentage of males submitted to surgical intervention (31/58; 53.4%) was higher than that of females (24/57; 42.1%), although the difference was not statistically significant (P=0.223). The mean gestational ages of the preterm neonates in groups S and NS were 27.1 and 27.7 weeks, respectively, while the average birth weight of group S was significantly (P=0.049) lower than that of group NS (Table 1). Of the neonates presenting low birth weight in the total study population, more than half (57.7%) were in group S but, according to the ROC curve, birth weight was not a good predictor (P=0.107) of surgical closure. There was no significant difference (P=0.155) between the surgical and non-surgical groups regarding DAD, however, the two groups were significantly (P=0.010) different with respect to the index DAD2/birth weight (Table 1). According to the percentage distributions shown in Table 2, preterm neonates with DAD2/birth weight index above 5 mm2/kg presented a 62.1% (P=0.006) probability of being submitted to surgical closure of PDA. Elevated probabilities of receiving surgical treatment for the correction of PDA were also associated with preterm neonates presenting LA:Ao ratios above 1.5 (72.2 % probability; P=0.001) or exhibiting high ductal shunting (61.2%; P=0.025). Mortality was not directly associated (P=0.151) with surgical closure, however, since the deaths of seven children from group S and of 13 children from group NS were caused by other factors including sepsis, complex congenital malformations and cerebral ventricular hemorrhage.

Table 1. Main characteristics of the preterm neonates diagnosed with patent ductus arteriosus submitted to surgical (group S) or non-surgical (group NS) treatment of the defect. Variable

Group S (n = 55) Minimum Maximum Mean ± SDa Birth weight (g) 520 1550 924.0 ± 224.3 Diameter of ductus arteriosus 1.2 3.8 2.2 ± 0.5 (DAD; mm) DAD2/birth weight (mm2/kg) 1.6 16.0 5.8 ± 2.5

Group NS (n = 60) Minimum Maximum Mean ± SDa 520 1540 1012.3 ± 242.8 0.9 3.2 2.0 ± 0.7 0.8 11.9 4.5 ± 2.6

*Differences are statistically significant at P<0.05 (Student t test), a Standard deviation

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P value* 0.049 0.155 0.010

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Braulio R, et al. - Indicators of surgical treatment of patent ductus arteriosus in preterm neonates in the first week of life

Table 2. Association between the indication for surgical closure of patent ductus arteriosus in a population of preterm neonates (N = 115) and the variables quotient of diameter of ductus arteriosus (DAD)2 and birth weight, left atrial-to-aortic root diameter ratio (LA:Ao), ductal shunting and mortality. Variable Group Sa (%) Group NSb (%) P value* 2 DAD /birth weight (n = 111) 0.006 ≤ 5 mm2/kg 35.8 64.2 > 5 mm2/kg 62.1 37.9 LA: Ao ratio (n = 110) 0.001 ≤ 1.5 39.2 60.8 > 1.5 72.2 27.8 Ductal shunting c (n = 104) 0.025 Low 44.4 55.6 Moderate 28.6 71.4 High 61.5 38.5 Mortality (n = 111) 0.151 Yes 12.7 23.2 No 87.3 76.8 a Group submitted to surgical treatment, b Group submitted to non-surgical treatment, c Ductal shunt was classified as low, moderate and high depending on the flow up to the proximal third, mid and distal third of the pulmonary artery, respectively. * Associations between the variables and indication for surgical closure of PDA are statistically significant at P < 0.05 (χ2 test)

Table 3. Multivariate logistic regression analysis (complete model) of the predictors of surgical closure among preterm neonates with patent ductus arteriosus (N = 115)

Table 4. Probability of surgical closure in preterm neonates with patent ductus arteriosus considering the combined factors left atrial-to-aortic root diameter ratio (LA:Ao) and occurrence of shock

Factor Estimated value P value Occurrence of shock 0.8705 0.1403 Drug therapy - 1.7907 0.2474 Administration of ibuprofen 0.9665 0.5367 Birth weight -0.5099 0.3899 Gestational age - 0.6106 0.2579 DAD2/kg a (mm2/kg) 0.3211 0.6405 LA:Ao ratio b 1.2918 0.0315 Ductal shunting 1.3257 0.0370 DA diameter - 0.7888 0.3207 a Quotient of diameter of ductus arteriosus (DAD)2 and birth weight, b Left atrial-to-aortic root diameter ratio (LA:Ao)

LA:Ao ratio Normal (≤ 1.5) Normal (≤ 1.5) Increased (> 1.5) Increased (> 1.5)

Multivariate logistic regression analysis of the predictors of surgical closure in 115 preterm neonates with PDA revealed that the variables LA:Ao ratio and ductal shunting were significant predictors of surgical closure (P=0.0315 and P=0.0370, respectively; Table 3). Moreover, the probability of surgical closure increased to 78.4% when the markers LA:Ao > 1.5 and shock were associated (Table 4).

Shock No Yes No Yes

Probability of surgical intervention (%) 23.4 48.5 54.2 78.4

is not always straightforward, particularly in the case of borderline patients. The consideration of various parameters has been proposed in the selection of preterm neonates requiring early surgical correction of PDA in order to prevent future heart problems and to ensure better chances of survival. Tschuppert et al. [1] indicated that a DAD2/birth weight index > 9 mm²/kg and a LA:Ao ratio > 1.5 represented good predictors of the need for surgery. The cut-off points obtained in the present study agree partially with the earlier proposals in that the suggested LA:Ao ratio cut-off was similar (> 1.5) but that for the DAD2/birth weight index was much smaller (> 5 mm2/kg). Furthermore, our results indicated that high ductal shunting is a relevant prognostic marker for surgical closure. According to Chiruvolu et al. [7], high left-to-right

DISCUSSION In the present study, 47.8% (55/115) of the preterm neonates diagnosed with PDA required surgical closure. The necessity for surgical intervention is decided mainly on clinical and echocardiographic assessment, but this decision

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shunting is very aggressive to preterm neonates because it induces pulmonary hypertension, pulmonary congestion and enlargement of heart chambers. A hemodynamically significant degree of ductal shunting may be a decisive factor in the choice of a surgical approach. The sample size employed in the present study was larger than that reported in earlier studies, and this improved the precision of the statistical analysis of parameters. Thus, the results obtained herein may be considered appropriate for the construction a checklist to serve as a guideline for pediatricians and cardiologists when arriving at decisions regarding surgical closure of PDA. Obviously, meticulous medical assessment on a case by case basis, coupled with sound and prudent judgment, must always prevail in decision making. However, it is important to emphasize that, while the short- and long-term benefits of PDA closure have been demonstrated by numerous studies [1-3,7,8], delays in the treatment of PDA may lead to severe consequences for the neonate.

REFERENCES 1. Tschuppert S, Doell C, Arlettaz-Mieth R, Baenziger O, Rousson V, Balmer C, et al. The effect of ductal diameter on surgical and medical closure of patent ductus arteriosus in preterm neonates: size matters. J Thorac Cardiovasc Surg. 2008;135(1):78-82. 2. Vida VL, Lago P, Salvatori S, Boccuzzo G, Padalino MA, Milanesi O, et al. Is there an optimal timing for surgical ligation of patent ductus arteriosus in preterm infants? Ann Thorac Surg. 2009;87(5):1509-15. 3. Noori S, McCoy M, Friedlich P, Bright B, Gottipati V, Seri I, et al. Failure of ductus arteriosus closure is associated with increased mortality in preterm infants. Pediatrics. 2009;123(1):e138-44. 4. Laborde F, Folliguet TA, Etienne PY, Carbognani D, Batisse A, Petrie J. Video-thoracoscopic surgical interruption of patent ductus arteriosus. Routine experience in 332 pediatric cases. Eur J Cardiothorac Surg. 1997;11(6):1052-5. 5. Khelashvili V, Gogorishili I, Metreveli I, Tsintsadze A, Botsvadze T. Patent ductus arteriosus endovascular closure by amplatzer duct occluder. Georgian Med News. 2006;(134):19-22.

CONCLUSION The parameters DAD2/birth weight index > 5 mm2/ kg and LA:Ao ratio > 1.5 along with high ductal shunting are statistically significant indicators (P<0.05) of the need for surgical closure of PDA in low birth weight preterm neonates during the first week of life. The probability of surgical intervention when any of these factors are present is greater than 60%. Moreover, when the LA:Ao ratio > 1.5 is associated with the occurrence of shock, the probability of surgical closure increases to 78.4%.

6. Su PH, Chen JY, Su CM, Huang TC, Lee HS. Comparison of ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants. Pediatr Int. 2003;45(6):665-70. 7. Chiruvolu A, Punjwani P, Ramaciotti C. Clinical and echocardiographic diagnosis of patent ductus arteriosus in premature neonates. Early Hum Dev. 2009;85(3):147-9. 8. Afiune JY, Singer JM, Leone CR. Echocardiographic post-neonatal progress of preterm neonates with patent ductus arteriosus. J Pediatr (Rio J). 2005;81(6):454-60.

Authors’ roles & responsibilities

9. Santos JLV, Braile DM, Ardito RV, Zaiantchick M, Soares MJF, Rade W, et al. Ligadura do canal arterial: tĂŠcnica extrapleural. Rev Bras Cir Cardiovasc. 1992;7(1):14-21.

RB Main author CLG Coauthor, statistical analysis FDRA Performed the echocardiograms KNB Performed the echocardiograms LDGA Conducted the data collection PHNC Conducted the data collection FDC Coauthor

10. Vicente WV, Rodrigues AJ, Ribeiro PJ, Evora PR, Menardi AC, Ferreira CA, et al. Dorsal minithoracotomy for ductus arteriosus clip closure in premature neonates. Ann Thorac Surg. 2004;77(3):1105-6.

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Santos AA, etORIGINAL al. - MortalityARTICLE risk is dose-dependent on the number of packed red blood cell transfused after coronary artery bypass graft

Mortality risk is dose-dependent on the number of packed red blood cell transfused after coronary artery bypass graft Risco de mortalidade é dose-dependente do número de unidades de concentrado de hemácias transfundidas após cirurgia de revascularização miocárdica

Antônio Alceu dos Santos1,2,3; Alexandre Gonçalves Sousa1; Raquel Ferrari Piotto1, PhD; Juan Carlos Montano Pedroso4, MSc

DOI: 10.5935/1678-9741.20130083

RBCCV 44205-1505

Abstract Introduction: Transfusions of one or more packed red blood cells is a widely strategy used in cardiac surgery, even after several evidences of increased morbidity and mortality. The world’s blood shortage is also already evident. Objective: To assess whether the risk of mortality is dose-dependent on the number of packed red blood cells transfused after coronary artery bypass graft. Methods: Between June 2009 and July 2010, were analyzed 3010 patients: transfused and non-transfused. Transfused patients were divided into six groups according to the number of packed red blood cells received: one, two, three, four, five, six or more units, then we assess the mortality risk in each group after a year of coronary artery bypass graft. To calculate the odds ratio was used the multivariate logistic regression model. Results: The increasing number of allogeneic packed red blood cells transfused results in an increasing risk of mortality, highlighting a dose-dependent relation. The odds ratio values

increase with the increased number of packed red blood cells transfused. The death’s gross odds ratio was 1.42 (P=0.165), 1.94 (P=0.005), 4.17; 4.22, 8.70, 33.33 (P<0.001) and the adjusted death’s odds ratio was 1.22 (P=0.43), 1.52 (P=0.08); 2.85; 2.86; 4.91 and 17.61 (P<0.001), as they received one, two, three, four, five, six or more packed red blood cells, respectively. Conclusion: The mortality risk is directly proportional to the number of packed red blood cells transfused in coronary artery bypass graft. The greater the amount of allogeneic blood transfused the greater the risk of mortality. The current transfusion practice needs to be reevaluated.

Hospital Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, São Paulo, SP, Brazil. 2 Associação Médica Brasileira (AMB), São Paulo, SP, Brazil. 3 Sociedade Brasileira de Cardiologia (SBC), São Paulo, SP, Brazil. 4 Sociedade Brasileira de Cirurgia Plástica (SBCP), São Paulo, SP, Brazil.

Correspondence address: Antônio Alceu dos Santos Rua 13 de Maio, 1838 - apto. 93 - Paraíso - São Paulo, SP Brazil – Zip code: 01327-002 E-mail: antonioalceu@cardiol.br

Descriptors: Blood transfusion. Mortality. Myocardial revascularization. Postoperative complications. Resumo Introdução: Transfusões de uma ou mais unidades de concen-

1

Work performed at the Hospital Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, São Paulo, SP, Brazil. Article received on September 1st , 2013 Article accepted on November 4th , 2013

No financial support.

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receberam uma, duas, três, quatro, cinco e seis ou mais unidades concentrado de hemácias e, após um ano da cirurgia de revascularização miocárdica, avaliamos o risco de mortalidade em cada grupo. Para obtenção do odds ratio foi utilizado modelo de regressão logística multivariado. Resultados: Transfusão crescente de unidades de concentrado de hemácias resulta em risco também crescente de mortalidade, evidenciando uma relação dose-reposta. Os valores do odds ratio aumentam com o acréscimo do número de unidades de hemácias alogênicas transfundidas. O risco de ocorrência de óbitos pelo odds ratio bruto foi 1,42 (P=0,165); 1,94 (P=0,005); 4,17; 4,22; 8,70, 33,33 (P<0,001) e o risco de mortalidade pelo odds ratio ajustado foi 1,22 (P=0,43); 1,52 (P=0,08); 2,85; 2,86; 4,91 e 17,61 (P<0,001), conforme receberam transfusão de uma, duas, três, quatro, cinco, seis ou mais unidades concentrado de hemácias, respectivamente. Conclusão: O risco de mortalidade é diretamente proporcional ao número de unidades de concentrado de hemácias transfundidas em cirurgia de revascularização miocárdica. Quanto mais sangue alogênico transfundido, maior o risco de mortalidade. A prática transfusional atual precisa ser reavaliada.

Abbreviations, acronyms & symbols AF AMI CPB CHF CKF CABG DM COPD EuroSCORE RBCT SAH

Atrial fibrillation Acute myocardial infarction cardiopulmonary bypass Congestive heart failure Chronic kidney failure Coronary artery bypass grafting Diabetes mellitus Chronic obstructive pulmonary disease European System for Cardiac Operative Risk Evaluation Red blood cell transfusion Systemic arterial hypertension

trado de hemácias é estratégia amplamente utilizada em cirurgia cardíaca, mesmo após várias evidências de aumento de morbimortalidade. A escassez de sangue no mundo também já é evidente. Objetivo: Avaliar se o risco de mortalidade é dose-dependente do número de unidades de concentrado de hemácias transfundidas após cirurgia de revascularização miocárdica. Métodos: Entre junho 2009 e julho 2010, foram analisados 3010 pacientes: transfundidos e não transfundidos. Pacientes hemotransfundidos foram divididos em seis grupos conforme

Descritores: Transfusão de sangue. Mortalidade. Revascularização miocárdica. Complicações pós-operatórias.

INTRODUCTION

Some authors have reported a greater mortality rate with the transfusion of a single unit of PRBC either in general surgery [13,14] and cardiac surgery [6]. However, in 2012, it was published the ACUITY study [15] demonstrating that the higher mortality rate in patients underwent CABG becomes more significant only with the transfusion of four or more units of PRBCs. Despite these data in the national and international literature, it is still not quite clear whether the greater risk of mortality related to RBCT is really a dose-dependent on the number of units of allogeneic red blood cell transfused. The aim of this study was to assess the impact on the risk of mortality in patients undergoing CABG after one year of the increasing number of PRBCs units transfused, compared to those patients not transfused.

Blood transfusions are a widely used medical practice in cardiac surgery, due to the occurrence of massive bleeding in this setting [1]. In some hospitals, the red blood cell transfusion (RBCT) occurs indiscriminately reaching to, in some sites, a rate of 92.8% of the surgical patients [2]. This transfusional practice has led to a blood component shortage in the blood banks worldwide [3]. In Brazil, this situation has become increasingly critical, and the noticed trend is getting worse, since that a trial performed in 2007 [4] reported that the country’s demand for blood grows at a rate of 1% while the offer grows at a range of 0.5% to 0.7% per year, thus indicating that in the near future we will have to get along with the possibility of no blood available for most medical procedures. In the literature the relationship between RBCT and increased clinical complications after cardiac surgery is already strongly established, such as infections, chronic kidney failure (CKF), congestive heart failure (CHF), atrial fibrillation (AF), stroke [5,6] malignancies [7]. In the last decade, several studies have shown reduced survival after transfusion of packed red blood cells (PRBCs) [6,8,9], especially with massive transfusions [6,10]. As evidenced in a recent study (2013), the allogeneic blood transfusion is an independent predictor of early and late mortality after coronary artery bypass grafting (CABG) [9]. These evidences help physicians to increasingly adopt a restrictive behavior regarding the RBCT [11,12].

METHODS We have built an electronic database, where we prospectively included the data of all the patients aged 18 or older, who underwent CABG procedure in the Hospital Beneficência Portuguesa of São Paulo from June 2009 to July 2010, and with one year follow-up after the surgery. This database contains data from 3010 patients undergoing CABG, which contemplates 69.6% of the total performed surgeries. The data collection form presented 243 variables with data collected from all the fourteen Cardiac Surgery teams of the Institution. All the information was maintained confidential, including the patients’ identity.

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For the objective of this study, we performed a retrospective review of this database. The total sample consisted of 3004 patients because six of them did not complete the followup of at least one year. The patients were divided into two groups, patients who did not receive PRBC transfusion and the patients who received PRBCs transfusion. Then, the transfused patients were subdivided into 6 groups: Group A, B, C, D, E and F, as they received one, two, three, four, five and six or more PRBCs units, respectively, in the intra and or post-cardiac surgery. After one year of postoperative, it was calculated the mortality risk (odds ratio) for each one of the groups. For this study were selected the following variables from the database: age, transfusion, smoking, diabetes mellitus (DM), dyslipidemia, systemic arterial hypertension (SAH), CKF, previous stroke, chronic obstructive pulmonary disease (COPD), peripheral arterial decease, cerebrovascular disease, CHF, acute myocardial infarction (AMI), arrhythmia, coronary intervention, previous coronary angioplasty, previous CABG, previous valvar surgery, previous noncardiac surgery, elective or urgent/ emergency surgery, type of graft (arterial/venous), use of cardiopulmonary bypass (CPB), and CABG, isolated or associated with other surgeries. The study was approved by the Research Ethics Committee of the Hospital Beneficência Portuguesa of São Paulo, under the protocol number 136.450.

surgery. Of those, 1,155 patients (61.2%) were male patients and 733 (38.8%) female patients. The age ranged from 31 to 89 years with a standard deviation of 9.37 years and a median of 64.01 years. The demographics data and characteristics of the transfused patients assessed in the study are described in Table 1. The average number of packed red blood cells units transfused per patient was 2.6 ± 2.4 (1-25) units. The transfusions of one, two and three units of PRBCs were the most common frequencies of the blood units transfused: 33.1%; 32.3% and 14.4%, respectively. They account for approximately 80% of the transfused patients who received 3 or less units of allogeneic blood (Figure 1). The group receiving no RBCT showed a total of 1,116 patients.

Table 1. Demographic values and characteristic description of transfused patients. Variable Category Age (years) Smoking DM Dyslipidemia CKF SAH Previous stroke COPD Peripheral arterial disease Cerebrovascular disease Coronary Intervention Previous CABG Previous valvar surgery Other surgeries Angioplasty Previous AMI CHF Arrhythmia Surgical indication Elective Urgent Emergency Graft type Arterial Venous Venous + Arterial CPB use CABG Isolate With heart surgery With other surgeries With valvar

Statistics considerations All the variables were assessed descriptively. For the quantitative variables, this analysis was performed by observing the minimum and maximum values, and the standard deviations and median, for the calculation of means. For the qualitative variables it was calculated the absolute and relative frequencies. To obtain death prognostic factors we used the regression logistic multivariate adjusted model [16], contemplating the variables that were showed in univariate previously performed, P<0.10: age ≥ 60 years, type of graft, isolated CABG, CHF, CKF, previous stroke, elective surgery, arrhythmia, previous CABG and previous valvar surgery, DM, previous myocardial infarction, use of CPB and number of PRBCs units transfused. Through the stepwise selection process, the selected variables were the number of packed red blood cells, isolated CABG, age, CHF, CKF, previous stroke and COPD. The significance level used for the tests was 5%. RESULTS

Descriptive values 64.0 ± 9.4 274 (14.5%) 738 (39.1%) 835 (44.2%) 145 (7.7%) 1599 (84.7%) 122 (6.5%) 158 (8.4%) 109 (5.8%) 28 (2.0%) 190 (10.1%) 35 (1.9%) 8 (0.4%) 4 (0.2%) 137 (7.3%) 867 (45.9%) 62 (3.3%) 120 (6.4%) 1865 (98.8%) 20 (1.1%) 3 (0.1%) 264 (14.0%) 274 (14.5%) 1349 (71.5%) 1724 (91.3%) 1636 (86.7%) 109 (5.8%) 33 (1.8%) 110 (5.8%)

DM – diabetes mellitus; CKF – chronic kidney failure; SAH – systemic arterial hypertension; COPD – chronic obstructive pulmonary disease; CABG – coronary artery bypass graft; AMI – acute myocardial infarction; CHF – congestive heart failure; CPB – cardiopulmonary bypass

A total of 4,936 units of packed red blood cells were transfused in 1888 patients during their hospital stay, which corresponds to 62.8% of the patients who underwent CABG

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Fig. 1 - Frequency histogram of the packed red blood cells units transfused

The overall mortality rate within the transfused patients group, in the period of one year after surgery, was 11.2 % (212 deaths), compared to only 3.3% (37 deaths) among the patients who did not receive blood transfusions. It was found that there is an increasing mortality risk in the groups with increased number of allogeneic PRBCs units transfused. The group that received a single unit of PRBCs (Group A) showed a mortality risk of 4.6% (29 deaths). The group B (2 PRBCs) presented a mortality risk of 6.2 % (38 deaths). The mortality risk within the group C (3 PRBCs) and group D (4 PRBCs) was 12.5 % (34 deaths) and 12.6 % (22 deaths), respectively. Among the patients who received transfusion of 5 PRBCs (Group E) was observed a high mortality risk of 22.9% [17] of deaths. The negative impact of the allogeneic red blood cell transfusions became more evident within the group of 6 or more units of PRBCs (Group F), where occurred 72 deaths, which represents the death of more than half (53.3%) of the patients. The result of a multivariate regression model analysis confirms that the presence of red blood cell transfusion is an independent predictor of mortality in CABG surgery, increasing significantly the risk of death at one year (OR 2.31​​; 95% CI 1.33-4.04; P=0.003). Table 2 shows the other variables related to greater mortality: age, prior stroke, CKF, COPD, CHF, peripheral arterial disease, type of CABG (with other surgeries). Through a logistic regression model, the odds ratio (OR) value was estimated for each one of the values ​​of PRBCs units transfused in the univariate analysis. The risk of mortality progressively increases according to the number of packed red blood cells transfused in the patient. As shown in Figure 2, with a single unit of PRBCs transfused there is an adverse

clinical outcome with a greater risk of mortality (OR 1.42; P=0.165). For the group that received two units of packed red blood cells, the risk of mortality was significantly greater with an odds ratio of 1.94 (P=0.005). The relationship between the risk of mortality and the number of units of allogeneic blood transfused becomes more evident when we analyze the other groups: Group C odds ratio of 4.17 (P<0.001); Group D odds ratio of 4.22 (P<0.001); Group E odds ratio of 8.70 (P<0.001); and finally, in the group that had received six or more units of packed red blood cells, we have a huge risk of mortality showing an odds ratio of 33.33 (P<0.001). As observed in Table 3, even with the multivariate logistic regression adjusted model, the risk of mortality has also shown to be dose-dependent on the number of allogeneic PRBCs units transfused. The adjusted odds ratio values also​​ increase according to the increase in the amount of packed red blood cells transfused. With one (group A) and two (group B) units of PRBCs it is also observed a greater likelihood of deaths occurrence, although not significant, yet with an odds ratio of 1.22 (P=0.435) and 1.52 (P=0.086), respectively. In the groups C, D and E, the risk of mortality has remained growing, with statistical significance, as exemplified by an odds ratio of 2.85 (P<0.001); 2.86 (P<0.001) and 4.91 (P<0.001), respectively. The group receiving six or more units of PRBCs transfused (Group F), resulted in a high risk of mortality with an odds ratio of 17.61 (P<0.001). Figure 3 shows a curve which estimates the likelihood of death occurrence through the number of PRBCs units transfused. It is noted that the estimated probability of death within one year from the CABG increases progressively according to the amount of allogeneic blood transfusion, so

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that, when eight units of PRBCs are transfused the patient’s probability of death is 50%, and with the transfusion of 25 units of PBRCs the possibility of death is 100%. In this study the risk of mortality has shown to be dose-dependent on the amount of allogeneic PRBCs units transfused after CABG surgery, being that, the higher the units of packed red blood cells transfused, the greater the risk of postoperative mortality at one year.

may explain the amount of blood transfusions performed in our study (4,936 units of packed red blood cells), is the study published in 2001 by DeFoe et al., where through a retrospective study, they found out that anemic patients (hematocrit below 22%), who underwent CABG surgery, were associated with greater operative mortality [19]. However, more recently that latter finding has been refuted, provide that, it has been demonstrated that even a hematocrit as low as 17%, in cardiac surgery, has not shown adverse impact on patients’ outcome [12]. For over half a century, both in our country and in the world, it has not been questioned such transfusion practice. However, in 2002, Engoren et al. [8] published one of the first large studies questioning the real benefits of the transfusional therapy in the cardiac surgery setting. The researchers have shown that even after correction for comorbidities and other factors, the blood transfusions are associated with a 70% increase in mortality. In a recent study it was demonstrated that the RBCT is an independent predictor for both, 30 day mortality (OR 2.00; P = 0.007) and one year mortality (OR 2.31; P = 0.003), after CABG surgery. Even in low-

DISCUSSION According to a study published in 2009 [17], about 85 million units of packed red blood cells are transfused annually, worldwide. This huge amount of blood used is still due to, among other factors, a 1942’s concept when John Lundy published an article without scientific evidence and based only on his experience, showing that the hemoglobin level of 10 g/dL (10/30 rule) would be the lowest limit to be tolerated by humans without life-threatening, to recommend an allogeneic blood transfusion [18]. In fact, this behavior still persists in the medical community. Another factor that

Table 2. Odds ratio values for the associated variables to 1 year mortality. Variable Age

CI at 95% Lower limit Upper limit 1.04 1.09

P* < 0.001

Category

Odds ratio 1.07

Transfusion

No Yes

1.00 2.31

1.33

4.04

0.003

CKF

No Yes

1.00 2.98

1.65

5.38

< 0.001

Previous stroke

No Yes

1.00 3.11

1.79

5.40

< 0.001

COPD

No Yes

1.00 2.86

1.69

4.83

< 0.001

Peripheral arterial disease

No Yes

1.00 2.26

1.23

4.14

0.008

CHF

No Yes

1.00 4.26

2.12

8.56

< 0.001

Isolate With valvar With other cardiac surgeries With non-cardiac surgeries

1.00 2.52 2.21 2.54

1.29 1.06 0.87

4.92 4.61 7.44

0.007 0.036 0.089

CABG

CI – confidence interval; CKF – chronic kidney failure; COPD – chronic obstructive pulmonary disease; CHF – congestive heart failure; CABG – coronary artery bypass graft; * probability’s descriptive level of the logistic regression model

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Fig. 2 - Univariate relationship between units of transfused PRBCs and subsequent 1 year mortality. PRBCs – packed red blood cells; CI – confidence interval; * probability’s descriptive level of the logistic regression model

1.77; P<0.0001) the risk of post-operative mortality, thus showing a dose-dependent relationship between the amount of PRBCs units transfused and the survival’s reduction. In 2012, Ferraris et al. [14] also demonstrated that there is a dose-response of adverse effects, including mortality, associated to the use of blood transfusions in 48,291 patients who underwent non-cardiac surgery. The authors have found that patients who received a single unit of PRBCs (31.4%) had presented greater morbidity and mortality, even after the use of propensity scores to control confounding variables. Similarly to the Koch et al. [6] studies, Stone et al. [15] have also found a dose-dependent relationship between the amount of PRBCs units transfused and the subsequent mortality. Although they have not observed the evidence of an impact on survival with transfusion of three or fewer units of PRBCs, Stone et al stated that one cannot rule out the occurrence of moderate adverse effect even with a smaller amount transfusion of blood. The data from this study corroborate with those that have been published by Koch et al. [6] and Ferraris et al. [14], demonstrating a direct relationship between the amount of PRBCs transfused and greater risk of death occurrence. Furthermore, this study has demonstrated an association between PRBCs transfusions and increased mortality risk, even with a lower number of packed red blood cells units transfused, fact that was not observed by Stone et al., but found by Koch et al. [6] and Ferraris et al. [14]. It has been confirmed that the mortality risk increases with the amount of allogeneic pack red blood cells units transfused. With the transfusion of a single unit of PRBCs, an adverse clinical outcome is already demonstrated, with greater likelihood of death occurrence, showing an odds ratio of 1.42. However, with the transfusion of two units of PRBCs the mortality risk was significantly greater with an odds ratio of 1.94. This deleterious effect risk becomes more

Fig. 3 - Estimated probability of death at 1 year of follow up with the number of units of PRBCs

risk patients (age <60 years and with EuroSCORE ≤ 2%), hence with fewer comorbidities, there were significantly more deaths in the transfused group within both periods 30 day (7.0% vs. 0.0%, P<0.001) and 1 year period (10.0% vs. 0.0%, P<0.001) [9]. Transfusions above four PRBCs units are associated with progressively greater mortality either in general surgery [13] and cardiovascular surgery [6,10,11,15]. In a prospective, randomized and controlled trial, it has become evident the increased mortality risk associated to the transfusions of 1-2, 3-4, 5-6 and > 6 units of packed red blood cells after cardiac surgery [11]. In the literature, there are other studies [15,20], which have also shown adverse clinical outcomes by the amount of PRBCs associated effect. Our study has shown the isolated adverse effect of every allogeneic PRBCs unit transfused in the patient’s population after one year of CABG surgery. In 2006, Koch et al. [6] by studying more than 5,000 transfused patients undergoing CABG surgery, concluded that every administered unit of PRBCs increases by 77% (OR

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significant as more units of PRBCs are transfused. Through the logistic regression model, we built a curve (Figure 3) to estimate the probability of death occurrence by using the number of PRBCs units transfused. It is observed that the mortality risk is progressively greater as the patient receives more allogeneic blood units. The results of this study have shown that there is a dose-response relationship between the number of PRBCs transfused and the increased mortality risk even after the correction of comorbidities (Table 3). The adjusted odds ratio values ​​increase with the increase on the number of packed red blood cells units transfused, starting at 1.22 level, for one PRBCs unit, and it gradually rises up to 4.91 (P<0.001), for five PRBCs units transfused. The group that received six or more units of packed red blood cells showed a high mortality risk with an odds ratio of 17.61 (P<0.001). The fact that we have not found statistical significance in groups A and B is believed to be related to the sample’s size of our study (1888 transfused patients). As already mentioned, other studies were able to demonstrate statistical significance in the risk of mortality, with a single unit of PRBCs in a relatively larger patients’ population undergoing blood transfusion [6]. The fact that most studies assessing the impact of blood transfusion on post-operative patient outcomes have a retrospective approach, and the concept that more severe ill patients receive more allogeneic blood, it becomes more difficult to establish a relationship between cause and effect. To establish whether a particular factor and clinical outcome is causal or merely an association, Austin Bradford Hill [21] proposed a set of nine criteria: strength of association, consistency, specificity, temporality, biological plausibility,

coherence, experimental evidences, and analogy and doseresponse. These criteria were employed to determine that the relationship between smoking and lung cancer is a causal relationship, since the completion of a randomized clinical trial would not be ethical for this purpose. The same approach applies to the case of blood transfusions. It would not be possible to conduct a randomized and placebo-controlled trial to assess the clinical effects of the increasing allogeneic transfusion of PRBCs. That makes the use of the Hill’s criteria particularly interesting. A careful analysis on the relationship between the blood transfusion and the adverse clinical outcome based on the Hill’s criteria, suggests that this is not just an association, but in fact, it is a cause and effect relationship. The data of this study corroborate to that conclusion. Several studies have demonstrated that blood transfusions result in increased morbidity risk of AF, CKF, stroke, CHF, infections and malignancies [5-7], consequently, these pathologies contribute to the increased risk of both early and late mortality. The exact mechanisms in which the homologous blood transfusions lead to the morbidity and mortality are not fully known, and several explanations have been suggested. During the storage, the red blood cells undergo a series of chemical and structural changes, such as depletion of adenosine triphosphate, reduction of 2,3diphosphoglycerate (2,3 DPG), and loss of elasticity. With only three hours of storage is already noted the nitric oxide’s falling of bioactivity in the red blood cells, which would result in decreased oxygen delivery in the microcirculation, and hence, adverse clinical outcomes [22]. Another explanation is the similarity between blood transfusion and transplantation. According to Flohe et al. [23], as in transplantation, the

Table 3. Gross and adjusted odds ratio values for mortality risk.

None PRBC 1 PRBC 2 PRBCs 3 PRBCs 4 PRBCs 5 PRBCs > 6 PRBCs Isolate CABG Age > 60 years CHF CKF Previous stroke COPD

Gross Odds ratio CI at 95% 1.00 1.42 (0.87; 2.34) 1.94 (1.22; 3.09) 4.17 (2.56; 6.78) 4.22 (2.43; 7.35) 8.70 (4.62; 16.38) 33.33 (20.81; 53.37) 0.26 2.78 6.22 4.48 2.62 2.95

(0.19; 0.36) (2.04; 3.80) (3.87; 10.00) (3.09; 6.49) (1.72; 3.98) (2.03; 4.28)

P* 0.165 0.005 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001

Adjusted Odds ratio CI at 95% 1.00 (0.74;2.03) 1.22 (0.94;2.44) 1.52 (1.72;4.73) 2.85 (1.60;5.09) 2.86 (2.52;9.57) 4.91 (10.65;29.13) 17.61 0.44 1.91 3.38 2.23 2.37 2.04

(0.31;0.63) (1.36;2.69) (1.92;5.96) (1.43;3.48) (1.47;3.83) (1.32;3.15)

P* 0.435 0.086 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.001

PRBCs – packed red blood cells; CABG – coronary artery bypass graft; CHF – congestive heart failure; CKF – chronic kidney failure; COPD – chronic obstructive pulmonary disease; CI – confidence interval; * probability’s descriptive level of the logistic regression model

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allogeneic transfusions may result in multiple inflammatory and immunological reactions. So, the greater PRBCs units transfused, the greater the charge of antigens injected into the patient’s circulation. Thus, from one side we have the hemolytic reactions and the other, the even more critical, the immunomodulation [7]. Therefore, increasing transfusion units of homologous blood may result in increasing mortality risk, as it has been shown by our study. It has still not known what is the lowest limit of hemoglobin and/or hematocrit that implies in life-threatening, to recommend a blood transfusion, without resulting in increased deleterious effects. Several strategies have been proposed to reduce allogeneic blood transfusions. Many of these measures involve optimizing the hematopoiesis; minimize the blood loss in surgeries; and mainly, to admit greater tolerance to anemia. A more restrictive approach to blood transfusion [12] can be well tolerated, and it has no adverse impact on the mortality. The acknowledgement of this fact would result in avoiding many unnecessary transfusions, since that, in most cases, is not the patient but the physician who does not tolerate the anemia. In another study it has become evident that a more conservative blood transfusion approach, in cardiac surgery with CPB, it does not alter the mortality rate among the groups of restrictive strategy (hematocrit ≥ 24%) and liberal strategy (hematocrit ≥ 30%) [11]. It is already known that patients with hematocrit below 40%, and need for cardiopulmonary bypass and multiple bypasses, have a greater likelihood to use blood in CABG surgery, therefore, to identify, treat and/or prevent these conditions will result in less use of blood products transfusion [20]. Souza & Braile [24] demonstrated that a hemoconcentration during the CPB associated to a reduced water balance, is also able to decrease the use of blood and plasma in cardiac surgery. Other interventions consist in the use of antifibrinolytic agents, such as epsilon-aminocaproic acid [25], making routine use of normovolemic hemodilution and total replacement of perfusate [26]. A study performed in patients undergoing CABG surgery without CPB, reported low rates of postoperative complications, less blood products transfusion, and lower mortality [27]. It is possible to reduce blood consumption by changing the transfusional practice. When you have the purpose and/ or the multidisciplinary willingness (surgeons, physicians, anesthesiologist, and intensive care physicians) to manage and conserve the autologous blood, it is possible to perform complex cardiac surgeries, such as a cardiac retransplantation, without the use of allogeneic blood transfusion [28]. Worldwide medical centers seek to establish protocols to ration the use of blood and it has become a hospital’s quality criteria to be pursued by the quality certifying agencies, such as the Joint Commission International [29]. Our study confirms the importance of achieving these goals by seeking treatment options to transfusion of blood products.

There are some limitations to our study. It is a retrospective study of a database; the blood transfusions performed on both intra- and postoperative settings did not have a hemoglobin minimum trigger, being the transfusions administered at the discretion of the patient’s physician responsible for care; and the storage time of the PRBCs units transfused was not taken into account, however this study refers to the current situation of the hospitals in our environment. A final limitation is that we have not differentiated the blood transfusions given during and after surgery since intraoperatively transfusions, especially with CPB, are more triggered by hemoglobin or hematocrit levels, and not by the patient’s clinical status. The advantages are: electronic database, which was filled out in a systematic way, and as well as the large number of assessed patients and the utilization of specific statistical methods to reduce the influence of confounding variables. CONCLUSION The mortality risk is dose-dependent on the number of allogeneic packed red blood cells units transfused after coronary artery bypass graft, therefore, as more units of PRBCs transfused, the greater the risk of postoperative mortality. It is a must to reassess the current transfusional practice and seek therapeutic options to blood products.

Authors' roles & responsibilities AAS AGS RFP JCMP

Literature research; database search, statistical analysis, analysis of results, writing of the manuscript, review of the manuscript Database search, analysis of results; correction of the manuscript Statistical analysis, review of the manuscript Bibliographic research, analysis of results, and review of the manuscript

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Gimenes C, et al. - Association of pre and intraoperative variables with ORIGINAL ARTICLE postoperative complications in coronary artery bypass graft surgery

Association of pre and intraoperative variables with postoperative complications in coronary artery bypass graft surgery Associação de variáveis pré e intraoperatórias com complicações pós-operatórias em cirurgia de revascularização do miocárdio

Camila Gimenes1, MD, PhD; Silvia Regina Barrile1, MD, PhD; Bruno Martinelli1, MD; Carlos Fernando Ronchi1, MD, PhD; Eduardo Aguilar Arca1, MD, PhD; Rodrigo Gimenes2, MD; Marina Politi Okoshi2, MD, PhD; Katashi Okoshi2, MD, PhD

DOI: 10.5935/1678-9741.20130084

RBCCV 44205-1506

Abstract Objective: To associate the pre- and intraoperative variables with postoperative complications of patients undergoing coronary artery bypass graft surgery. Methods: The pre- and intraoperative risk factors of individuals of both genders with diagnosis of coronary insufficiency undergoing coronary artery bypass graft have been studied. Results: Fifty-eight individuals with median age 62 ± 10 yearold were included in the study, 67% of whom were male. Fourteen (24.1%) patients were smokers, 39 (67.2%) had previous myocardial infarction history, 11 (19%) had undergone coronary angioplasty, 74% had hypertension, 27% had diabetes mellitus, 64% had dyslipidemia and 15.5% had chronic obstructive pulmonary disease. Eighteen (31%) patients presented postoperative complications, most frequent being: infection in surgical incision, difficulties in deambulation, dyspnea, urinary infection and generalized weakness. Male patients had fewer complications than females (P=0.005). Patients with chronic obstructive pulmonary disease remained hospitalized for longer time periods (P=0.019).

Postoperative complications occurred in 50% of the patients with creatinine increased, while only 27.1% of the patients with normal value of creatinine had complications (P=0.049). In addition, complications occurred in 50% of the patients with diabetes mellitus, while only 23.8% of patients without diabetes mellitus had complications (P=0.032). The intraoperative factors showed no statistically significant differences. Conclusion: The preoperative factors are associated with postoperative complications in patients undergoing coronary artery bypass graft surgery.

Universidade Sagrado Coração (USC), Bauru, SP, Brazil. Faculdade de Medicina de Botucatu (FMB), Botucatu, SP, Brazil.

Correspondence address: Camila Gimenes Universidade Sagrado Coração Rua Irmã Arminda, 10-50 – Jardim Brasil – Bauru, SP, Brazil Zip code: 17011-160 E-mail: camilagimenes@ymail.com

1 2

Descriptors: Myocardial revascularization. Coronary artery bypass. Postoperative complications. Risk factors. Resumo Objetivo: Associar variáveis pré e intraoperatórias com as complicações pós-operatórias de pacientes submetidos à cirurgia de revascularização miocárdica.

Work carried out at Universidade Sagrado Coração (USC), Bauru, SP, Brazil.

Article received on February 26th, 2013 Article accepted on May 5th, 2013

Financial Support: CAPES.

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Gimenes C, et al. - Association of pre and intraoperative variables with postoperative complications in coronary artery bypass graft surgery

rial, 27% diabetes mellitus, 64% dislipidemia e 15,5% doença pulmonar obstrutiva crônica. Dezoito (31%) pacientes apresentaram complicações no pós-operatório e as mais frequentes foram infecção na incisão cirúrgica, dificuldades na deambulação, dispneia, infecção urinária e fraqueza generalizada. Pacientes do sexo masculino apresentaram menos complicações que os do sexo feminino (P=0,005). Pacientes com diagnóstico de doença pulmonar obstrutiva crônica permaneceram maior tempo hospitalizados (P=0,019). Complicações pós-operatórias ocorreram em 50% dos pacientes com creatinina aumentada, enquanto que apenas 27,1% dos pacientes com valor normal de creatinina apresentaram complicações (P=0,049). Ocorreram também complicações em 50% dos pacientes com diabetes mellitus, enquanto que apenas 23,8% dos pacientes sem diabetes mellitus tiveram complicações (P=0,032). Os fatores intraoperatórios não apresentaram diferenças significativas estatisticamente. Conclusão: Os fatores pré-operatórios estão associados com complicações pós-operatórias em pacientes submetidos à cirurgia de revascularização miocárdica.

Abbreviations, acronyms & symbols AMI BMI CABG COPD CPB DM ICU MV POD SAH

Acute myocardial infarction Body mass index Coronary artery bypass graft Chronic obstructive pulmonary disease Cardiopulmonary bypass Diabetes mellitus Intensive care unit Mechanical ventilation Postoperative day Systemic arterial hypertension

Métodos: Foram estudados os fatores de risco pré e intraoperatórios de indivíduos de ambos os sexos, com diagnóstico de insuficiência coronariana, submetidos à cirurgia de revascularização do miocárdio. Resultados: Participaram do estudo 58 indivíduos, com idade média de 62 ± 10 anos e 67% eram do sexo masculino. Catorze (24,1%) pacientes eram fumantes, 39 (67,2%) apresentavam história de infarto do miocárdio prévia, 11 (19%) tinham realizado angioplastia coronariana, 74% apresentavam hipertensão arte-

Descritores: Revascularização miocárdica. Ponte de artéria coronária. Complicações pós-operatórias. Fatores de risco.

INTRODUCTION

age, previous lung disease, smoking, poor nutritional status, impaired lung function, and associated comorbidities, that is, factors that lead to changes in the integrity of the respiratory system and may compromise respiratory mechanics and gas exchange [7]. In intraoperative factors, such as anesthetic induction, surgical incision, and the use of CPB can exacerbate respiratory impairment [5]. It is known that the appropriate control of the factors present in the preoperative period as well as the attempt to guarantee intraoperative stability, can ensure a good postoperative evolution by decreasing the occurrence of complications [8]. The objective of this study was to associate the pre-and intraoperative variables with postoperative complications of patients undergoing coronary artery bypass graft surgery.

Cardiovascular diseases were considered the main cause of death and disability worldwide in 2010 and represent the highest costs for medical care. In Brazil, according to DATASUS, in 2000, 946,392 death certificates were filed, with 260,595 (27.5%) reporting cardiocirculatory disease diagnosis [1]. Clinical manifestations can be controlled through different therapeutics, coronary artery bypass graft surgery (CABG) being one of them. This surgery is effective in improving quality of life and it can extend the survival of patients with coronary artery disease. It is performed when lifetime probability is greater with the surgical treatment than with clinical treatment [2,3]. The CABG is a complex procedure, which implies physiological changes, and it imposes great organic stress. Its results are influenced by the clinical characteristics of patients and by aspects inherent to the surgical procedure and cardiopulmonary bypass (CPB) [4]. Patients undergoing sternotomy, associated with immobility in bed, pain and temporary dysfunction of diaphragm muscle, show pulmonary dysfunction in postoperative. In addition, typically they show advanced age, prior cardiac complications (unstable angina, triple vessels disease, previous revascularization, left ventricular dysfunction), and other related diseases [systemic arterial hypertension (SAH), diabetes mellitus (DM) and peripheral vascular disease], featuring a population of greater severity [5,6]. The main risk factors studied in preoperative are advanced

METHODS Adult patients of both sexes undergoing CABG were studied in two private hospitals in Bauru, SP, from November 2005 to March 2008. The research project was approved by the Ethics in Research Committee of Sacred Heart University of Bauru under the protocol number 16/07, in accordance with the Declaration of Helsinki. Patients were previously informed about the research and they signed the consent form after their acceptance. Individuals with coronary insufficiency undergoing elective CABG were part of the sample, and their surgical access was by median sternotomy, with the use of cardiopulmonary bypass. Patients in New York Heart Association functional

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class IV heart failure and Canadian Cardiovascular Society class IV angina did not participate in the study. The study started with an interview with the patients the day before the surgery and the analysis of their respective medical records. All data collected were included in a detailed evaluation form containing personal data, diagnosis, risk factors for coronary artery disease (SAH, DM, dyslipidemia, smoking), functional classification of heart failure and angina severity, and related diseases. The results of the following preoperative supplementary exams were recorded: creatinine, hemoglobin, hematocrit and coronary angiography. Information about the surgery, such as number of grafts, CPB duration, and mechanical ventilation was obtained. Weaning from mechanical ventilation was performed in accordance with criteria for extubation adopted by the medical staff. From the first day after extubation, the patients began the sessions of physiotherapy, following the protocol adapted by the hospital physiotherapist staff, which consisted of lung reexpansion with breathing patterns, respiratory incentivator, orthostatism, and deambulation once a day [9]. The following information was obtained regarding the postoperative period: amount of blood received, hospital stay and complications presented by the patient. The variables of the preoperative, intraoperative, and postoperative periods were categorized to facilitate statistical analysis. Age was divided into four categories: 40-50 years, 50-60 years old, 60-70 years old and above 70 years old. Variables related to risk factors such as preoperative SAH, DM, dyslipidemia, and chronic obstructive pulmonary disease (COPD) as well as sex, acute myocardial infarction (AMI) and angioplasty variables were divided into mutually exclusive categories. Smoking was categorized as nonsmokers, current smokers and former smokers. Heart failure and angina were distributed according to their functional class. For body mass index (BMI), individuals were classified as normal, overweight or obese. For arterial lesions, reporting of single, double or triple coronary lesions was considered. Hemoglobin and hematocrit values were considered normal according to age and sex. For creatinine values, references between 0.7 to 1.3 mg/dL for men and 0.6 to 1.2 mg/dL for women were used; values above the references were deemd increased. Cutoffs for the CPB time were: less than or equal to 120 minutes and greater than 120 minutes. Duration of mechanical ventilation (MV) was less than or equal to 12 hours or longer than 12 hours. The variable discharge was categorized as: up to 9th postoperative day (POD), 10th to 16th POD and above 17th POD. The postoperative complications were divided into nine categories (uncomplicated, urinary tract infection, mental confusion, infection in surgical incision, difficulty walking, renal dysfunction, respiratory problems, dyspnea, and abnormal chest radiograph), generalized weakness, stroke, and respiratory

failure. The amount of blood received in the postoperative period was recorded as: up to four bags or above four bags. Statistical analysis was performed using the statistical program Past (Paleontological Statistics software package for education and data analysis) version 2.15. The data are presented as average and standard deviation and absolute and relative frequencies. The preoperative and intraoperative variables were associated with postoperative complications by chi-square test with continuity correction for comparisons of proportion. When the frequencies were less than five the Fisher exact test was used. Associations of variables with more than three categories were analyzed using ANOVA. The significance level adopted was 5%. RESULTS Fifty-eight subjects were included in the study with a mean age of 62 ± 10 years old and the majority were male (67.2%). Patient characteristics are shown in Table 1. In terms of heart failure classification, in accordance with the New York Heart Association, three (5.2%) patients were in class I, 37 (63.8%) in class II, and 16 (31%) in class III. Regarding angina severity, five patients (8.6%) were in class I, 35 (60.3%) in class II and 18 (31%) in class III, in accordance with the Canadian Cardiovascular Society. Eighteen (31%) patients presented postoperative complications. The most frequent complication were: infection in the surgical incision in six patients, difficulties in deambulation in four patients, dyspnea in four patients, urinary infection in three patients, and generalized weakness in three patients. Table 1. Patient characteristics Variables Values Gender (male/female) 39 (67.2%) 19 (32.8%) Age (years) 62±10 BMI (kg/m2) 28±3.8 Smoking Smokers 14 (24.1%) Ex-smokers 20 (34.5%) Nonsmokers 24 (41.4%) Myocardial infarction 39 (67.2%) Angioplasty 11 (19%) Coronary angiographies One-vessel 5(8.6%) Two-vessel 16 (27.6%) Three-vessel 37 (63.8%) Comorbidities SAH 43 (74.1%) DM 16 (27.6%) Dyslipidemia 37 (63.8%) COPD 9 (15.5%) Data expressed as mean ± standard deviation or n (%). BMI: body mass index; COPD: chronic obstructive lung disease; DM: diabetes mellitus; SAH: systemic arterial hypertension

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Cardiopulmonary bypass time was 102 ± 25 minutes and the MV time was 15 ± 4 hours, not including the ventilation time of a patient who needed reintubation and respiratory support. Male patients had fewer complications than female patients (20.5% and 52.5%, respectively; P=0.005). These patients had one or more of the following complications: infection in the surgical incision, stroke, respiratory or urinary infection, renal dysfunction, difficulty in deambulation, dyspnea, generalizated weakness and mental confusion. Individuals with COPD remained hospitalized for a longer period of time (P=0.019). While 94% of the individuals without COPD, were discharged by the 10th PO, only 66.6% of the COPD patients were discharged in the same time period. In 50% of the patients with elevated creatinine levels, complications such as renal dysfunction, infection in the surgical incision, mental confusion, and difficulty walking were observed, whereas only 27.1% of the patients with normal creatinine levels had complications (P=0.049). In addition, there were complications in eight (50%) patients with DM, such as urinary tract infection, infection in the surgical incision, dyspnea, and generalized weakness; 32 patients without DM (23.8%) had complications (P=0.032). As far as the number of grafts received, 25 patients received four grafts, 23 patients received three, six patients received two and four patients received five grafts. The medical records had no information as to what kind of grafts they were. Postoperative complications were not associated with the presence of previous AMI, heart failure or severe angina, smoking, previous angioplasty, SAH presence, DM or dyslipidemia, hemoglobin and hematocrit levels, or CPB and mechanical ventilation times.

Tu et al. [16] evaluated postoperative hospital stay in the intensive care unit (ICU) and global postoperative hospital stay and they determined that postoperative hospital stay ≥ 6 days in the ICU and ≥ 17 days in the hospital would be extended linked to the presence of complications. Ducci et al. [17] found an average of 8 days of hospital stay in his study with patients undergoing CABG, a similar result to ours, in which 89.6% of the patients were discharged by the 9th postoperative day. Guimarães et al. [18] reported that 45.5% of the patients showed postoperative complications, a higher frequency than our study in which 31% had one or more complications. The complications can be classified into pulmonary, renal, cardiac, neurological and infectious [19]. In our study, the infectious and pulmonary complications were observed more frequently. Most studies include being female as a risk factor for complications and mortality in heart surgery. Women have higher comorbidity conditions such as congestive heart failure, Braunwald class IIIB and IIIC angina, as well as kidney failure, and, typically, they are subjected to surgery when they are older. In addition, inadequate or inappropriate approach to chest pain occurs more frequently in women, resulting in bias in the evaluation and delayed diagnosis and treatment [12,14,19,20]. These data corroborate with the present study in which women presented a higher frequency of one or more complications. The incidence of complications in diabetic patients found in our study corroborates the findings of Ledur et al. [21] that showed the disadvantage of diabetics compared with patients without DM on the risk of any infection in postCABG. Predisposition to diabetic inflammatory processes may occur due to an increase in pro-inflammatory markers and a decrease in inflammatory proteins [22]. Smoking is associated with postoperative pulmonary complications, especially increased mechanical ventilation time, pneumonia, infection, and slower healing [23]. The respiratory system of smokers is compromised, which hinders alveolar ventilation after extubation. Our results showed no statistically significant difference between smokers and nonsmokers. The use of CPB is associated with postoperative bleeding, which can occur due to the increase in the use of clotting factors, hemodilution, hypothermia and, mainly, due to the inflammatory response. Besides CPB, other factors are associated with the need for blood transfusions, including: low body mass index, low levels of hematocrit and hemoglobin preoperatively, age over 74 years old and severe left ventricular dysfunction [24]. In our study, CPB time showed no statistically significant differences when associated with the amount of blood received postoperatively. In terms of renal function, Higgins et al. [25] showed increased risk of postoperative mortality in patients with serum creatinine ≥ 1.9 mg/dl and moderate risk between 1.6

DISCUSSION In this study with 58 patients, a predominance of males and a median age of 62 years old was observed, which is similar to other studies in terms of sex and age characterization associated with cardiovascular risk [10,11]. The median age of patients undergoing CABG has increased over the years, from 58.5 years old in the 1980s to 64.1 years old in the 1990s [12]. In this study, 27.6% of the patients were older than 70 years old. Performing CABG in increasingly elderly individuals means more intense care due to the greater number of postoperative complications that occur in this age group, with a consequent increase in on-call time in the hospital. Other factors associated with advanced age can further increase the patient's hospital stay [6,13]. Parsonnet et al. [14] and Hannan et al. [15] found increased risk only in the age group over 70 and 80 years old, respectively. In our study, 56% of the patients over 70 years old presented one (44%) or more (12%) postoperative complications.

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and 1.8 mg/dl. In this study, 50% of the patients with elevated creatinine showed increased postoperative complications. The presence of dyslipidemia or SAH in preoperative was not significantly related to complications in our study. However, the presence of COPD, DM or renal dysfunction (increase in creatinine) were associated with increased complications, in accordance with literature data [12,14,19,22,25]. The literature reports, as well as the results of this study shows that the preoperative clinical condition of the patient is the main determining factor of surgical results. Clinical instability before surgery is the most important risk component for the results of the surgical procedure. Risk prediction based on a good pre-operative evaluation is essential to quantify the severity of the patient and to make it possible to plan for the care to be provided. These kind of care are associated with better intraoperative and clinical condition on the postoperative period of the patient.

2. Feier FH, Sant’Anna RT, Garcia E, Bacco F, Pereira E, Santos M, et al. Influências temporais nas características e fatores de risco de pacientes submetidos a revascularização miocárdica. Arq Bras Cardiol. 2006;87(4):439-45. 3. Cavenaghi S, Ferreira LL, Marino LH, Lamari NM. Respiratory physiotherapy in the pre and postoperative myocardial revascularization surgery. Rev Bras Cir Cardiovasc. 2011;26(3):455-61. 4. Eagle KA, Guyton RA, Davidoff R, Ewy GA, Fonger J, Gardner TJ, et al. ACC/AHA Guidelines for Coronary Artery Bypass Graft Surgery: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery). American College of Cardiology/American Heart Association. J Am Coll Cardiol. 1999;34(4):1262-347. 5. Guizilini S, Gomes WJ, Faresin SM, Carvalho ACC, Jaramillo JI, Alves FA, et al. Efeitos do local de inserção do dreno pleural na função pulmonar no pós-operatório de cirurgia de revascularização do miocárdio. Rev Bras Cir Cardiovasc. 2004;19(1):47-54.

CONCLUSION In conclusion, this study shows that there is association between preoperative factors and postoperative complications in patients undergoing coronary artery bypass graft surgery.

6. Panesar SS, Athanasiou T, Nair S, Rao C, Jones C, Nicolaou M, et al. Early outcomes in the elderly: a meta-analysis of 4921 patients undergoing coronary artery bypass grafting comparison between offpump and on-pump techniques. Heart. 2006;92(12):1808-16.

Authors’ roles & responsibilities CG SRB BM CFR EAA RG MPO KO

7. Pereira ED, Fernandes AL, Silva Anção M, Araúja Pereres CP, Atallah AN, Faresin SM. Prospective assessment of the risk of postoperative pulmonary complications in patients submitted to upper abdominal surgery. São Paulo Med J. 1999;117(4):151-60.

Design and planning of the work, interpretation of the evidence, drafting and revision of the preliminary and final versions, and approved the final draft Design and planning of the work, interpretation of the evidence, drafting and revision of the preliminary and final versions, and approved the final draft Interpretation of the evidence, drafting of the preliminary and final versions, and approved the final draft Interpretation of the evidence, drafting of the preliminary and final versions, and approved the final draft Interpretation of the evidence, drafting of the preliminary and final versions, and approved the final draft Drafting of the preliminary and final versions, and approved the final draft Drafting of the preliminary and final versions, and approved the final draft Design and planning of the work, interpretation of the evidence, drafting and revision of the preliminary and final versions, and approved the final draft

8. Bianco ACM. Insuficiência respiratória no pós-operatório de cirurgia cardíaca. Rev Soc Cardiol Estado de São Paulo. 2001;11(5):927-40. 9. Taniguchi LNT, Pinheiro AP. Particularidades do atendimento ao paciente em pós-operatório de cirurgia cardíaca. In: Regenga MM, ed. Fisioterapia em cardiologia da UTI à reabilitação. São Paulo: Roca;2000. p.121-54. 10. Bastos PG, Sun X, Wagner DP, Knaus WA, Zimmerman JE. Application of the APACHE III prognostic system in Brazilian intensive care units: a prospective multicenter study. Intensive Care Med. 1996;22(6):564-70.

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1. Ministério da Saúde/Funasa/CENEP/Sistema de Informações de Mortalidade (SIM) e IBGE. Acessed on: March 28th, 2010. Available at: www.datasus.gov.br

12. Edwards FH, Clark RE, Schwartz M. Coronary artery bypass grafting: the Society of Thoracic Surgeons National Database experience. Ann Thorac Surg. 1994;57(1):12-9.

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13. Sales FM, Santos I. Perfil de idosos hospitalizados e nível de dependência de cuidados de enfermagem: identificação de necessidades. Texto Contexto Enferm. 2007;16(3):495-502.

Morbidity and duration of ICU stay after cardiac surgery. A model for preoperative risk assessment. Chest. 1992;102(1):36-44.

14. Parsonnet V, Bernstein AD, Gera M. Clinical usefulness of riskstratified outcome analysis in cardiac surgery in New Jersey. Ann Thorac Surg. 1996;61(2 Suppl):S8-11.

20. Almeida FF, Barreto SM, Couto BRGM, Starling CEF. Fatores preditores na mortalidade hospitalar e de complicações peroperatórias graves em cirurgia de revascularização miocárdica. Arq Bras Cardiol. 2003; 80(1):41-50.

15. Hannan EL, Kilburn H Jr, O’Donnell JF, Lukacik G, Shields EP. Adult open heart surgery in New York State. An analysis of risk factors and hospital mortality rates. JAMA. 1990;264(21):2768-74.

21. Ledur P, Almeida L, Pellanda LC, Schaan BD. Predictors of infection in post-coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2011;26(2):190-6.

16. Tu JV, Jaglal SB, Naylor CD. Multicenter validation of a risk index for mortality, intensive care unit stay, and overall hospital lenght of stay after cardiac surgery. Steering Committee of the Provincial Adult Cardiac Care Network of Ontario. Circulation. 1995;91(3):677-84.

22. Pauli JR, Cintra DE, Souza CT, Ropelle ER. New mechanisms by which physical exercise improves insulin resistance in the skeletal muscle. Arq Bras Endocrinol Metabol. 2009;53(4):399-408. 23. Hall TS, Brevetti GR, Skoultchi AJ, Sines JC, Gregory P, Spotnitz AJ. Re-exploration for hemorrhage followinh open heart surgery differentiation on the causes of bleeding and the impact on patient outcomes. Ann Thorac Cardiovasc Surg. 2001;7(6)352-7.

17. Ducci JA, Padilha KG, Telles SCR, Gutierrez BA. Gravidade de pacientes e demanda de trabalho de Enfermagem em Unidade de Terapia Intensiva: análise evolutiva segundo o TISS-28. Rev Bras Ter Intensiva. 2004;16(1):22-7.

24. Souza HJ, Moitinho RF. Strategies to reduce the use of blood components in cardiovascular surgery. Rev Bras Cir Cardiovasc. 2008;23(1):53-9.

18. Guimarães RCM, Rabelo ER, Moraes MA, Azzolin K. Gravidade de pacientes em pós-operatório de cirurgia cardíaca: uma análise evolutiva segundo o TISS-28. Rev Latino-Am Enfermagem. 2010;18(1):61-6.

25. Higgins TL, Estafanous FG, Loop FD, Beck GJ, Blum JM, Paranandi L. Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients. A clinical severity score. JAMA. 1992;267(17):2344-8.

19. Tuman KJ, McCarthy RJ, March RJ, Najafi H, Ivankovich AD.

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Reichert K, et al. - Development of cardioplegic solution without potassium: EXPERIMENTAL WORK experimental study in rat

Development of cardioplegic solution without potassium: experimental study in rat Desenvolvimento de solução cardioplégica sem potássio: estudo experimental em ratos

Karla Reichert1, Helison Rafael Pereira do Carmo1, Fany Lima1, Anali Galluce Torina1, Karlos Alexandre de Souza Vilarinho1, PhD; Pedro Paulo Martins de Oliveira1, PhD; Lindemberg Mota Silveira Filho1, PhD; Elaine Soraya Barbosa de Oliveira Severino1, PhD; Orlando Petrucci1, MD, PhD

DOI: 10.5935/1678-9741.20130085

RBCCV 44205-1507

Abstract Introduction: Myocardial preservation during open heart surgeries and harvesting for transplant are of great importance. The heart at the end of procedure has to resume its functions as soon as possible. All cardioplegic solutions are based on potassium for induction of cardioplegic arrest. Objective: To assess a cardioplegic solution with no potassium addition to the formula with two other commercially available cardioplegic solutions. The comparative assessment was based on cytotoxicity, adenosine triphosphate myocardial preservation, and caspase 3 activity. The tested solution (LIRM) uses low doses of sodium channel blocker (lidocaine), potassium channel opener (cromakalin), and actin/myosin cross bridge inhibitor (2,3-butanedione monoxime). Methods: Wistar rats underwent thoracotomy under mechanical ventilation and three different solutions were used for "in situ" perfusion for cardioplegic arrest induction: Custodiol (HTK), Braile (G/A), and LIRM solutions. After cardiac arrest, the hearts

were excised and kept in cold storage for 4 hours. After this period, the hearts were assessed with optical light microscopy, myocardial ATP content and caspase 3 activity. All three solutions were evaluated for direct cytotoxicity with L929 and WEHI-164 cells. Results: The ATP content was higher in the Custodiol group compared to two other solutions (P<0.05). The caspase activity was lower in the HTK group compared to LIRM and G/A solutions (P<0.01). The LIRM solution showed lower caspase activity compared to Braile solution (P<0.01). All solutions showed no cytotoxicity effect after 24 hours of cells exposure to cardioplegic solutions. Conclusion: Cardioplegia solutions without potassium are promised and aminoacid addition might be an interesting strategy. More evaluation is necessary for an optimal cardioplegic solution development.

Faculdade de Ciências Médicas da Universidade Estadual de Campinas (FCM-Unicamp), Campinas, SP, Brazil.

Correspondence address: Orlando Petrucci Rua João Baptista Geraldi, 135 – Campinas, SP Brazil – Zip code: 13085-020 E-mail: orlando@fcm.unicamp.br

Descriptors: Heart arrest, induced. Ischemia. Myocardial ischemia.

1

Work carried out at the Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Campinas, SP, Brazil. This work was funded by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) grant number 2012/09130-1

Article received on May 21th, 2013 Article accepted on September 9th, 2013

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Métodos: Ratos Wistar foram submetidos à toracotomia sob ventilação mecânica e três soluções diferentes foram utilizadas para perfusão in situ para a indução de parada cardioplégica: soluções Custodiol (HTK) Braile (G/A) e LIRM. Após parada cardíaca, os corações foram retirados e mantidos em câmara fria por 4 horas. Após esse período, o coração foi avaliado com microscopia de luz ótica, o conteúdo de ATP miocárdico e atividade da caspase 3. Todas as três soluções foram avaliadas quanto à citotoxicidade direta com células L929 e WEHI-164. Resultados: A quantidade de ATP foi maior no grupo Custodiol em comparação às com outras duas soluções (P<0,05). A atividade de caspase foi menor no grupo HTK quando comparado às soluções LIRM e G/A (P<0,01). A solução LIRM demonstrou menor atividade da caspase em comparação à solução Braile (P<0,01). Todas as soluções não mostraram qualquer efeito de citotoxicidade após 24 horas de exposição das células às soluções cardioplégicas. Conclusão: Soluções cardioplégicas sem potássio são uma perspectiva e a adição de aminoácido pode ser uma estratégia interessante. Mais avaliações são necessárias para o desenvolvimento ideal da solução cardioplégica.

Abbreviations, acronyms & symbols ANOVA ATP G/A HE HTK

Analysis of variance Adenosine triphosphate Glutamate/aspartate cardioplegic solution Hematoxylin and eosin Histidine-tryptophan cardioplegic solution

Resumo Introdução: Preservação do miocárdio durante cirurgias cardíacas abertas e de colheita para transplante são de grande importância. O coração ao final do processo tem de retomar as suas funções, logo que possível. Todas as soluções cardioplégicas são baseadas em potássio, para indução de parada cardioplégica. Objetivo: Comparar a uma solução cardioplégica sem adição de potássio à sua fórmula com duas outras soluções cardioplégicas disponíveis comercialmente. A avaliação comparativa foi baseada na citotoxicidade, preservação miocárdica (adenosina trifosfato, ATP) e atividade da caspase 3. A solução testada (LIRM) utiliza baixas doses de bloqueador de canal de sódio (lidocaína), abridor do canal de potássio (cromacalina) e inibidor da ponte actina / miosina (2,3-butanodiona monoxima).

Descritores: Parada cardíaca induzida. Isquemia. Isquemia miocárdica.

INTRODUCTION

The relative benefits provided by different cardioplegic solutions remain unclear. We idealized a new, potassium-free cardioplegic solution, named LIRM solution, containing: cromakalim, a potassium adenosine triphosphate (ATP)-channel opener that causes hyperpolarization of the cell membrane and coronary artery vasodilation [8]; lidocaine, a sodiumchannel blocker that inhibits sodium influx into the myocyte and depolarization of the cell membrane [9]; and 2,3-butanedione, a direct myofilament inhibitor that prevents myocyte contraction by desensitizing the myofilament calcium [10]. In the present study, we tested the myocardial protection afforded by the LIRM solution in terms of the ATP myocardial content and caspase 3 activity, which are important factors for short- and long-term outcomes for heart transplant and conventional open-heart surgeries [4,11-13]. We compared the myocardial protection results among the LIRM, histidine-tryptophan (HTK), and glutamate/aspartate (G/A) cardioplegic solutions after 4 hours of cold storage.

Elective cardiac arrest was first performed by global myocardial ischemia with aortic cross-clamping in combination with hypothermia, as reported by Lewis & Taufic [1]. Since then, complex open-heart surgeries with longer aortic cross-clamp periods have been developed. However, the use of longer cross-clamp periods has increased the incidence of ischemia/reperfusion injury. In 1955, Melrose et al. [2] introduced the concept of pharmacologic cardiac arrest, named cardioplegia, which could be obtained by using a solution with a high potassium concentration. Cardioplegic solutions with moderate potassium concentrations were introduced into surgical practice in the mid-1970s and have remained the gold standard for myocardial protection [3,4]. Today, most cardiac surgeries are performed by cardiopulmonary bypass with pharmacologic cardioplegic arrest. The elevated extracellular potassium level provided by the cardioplegic solution shifts the resting myocyte membrane potential from -85 mV to a range between -65 and -40 mV. This shift inactivates the fast sodium channels, thereby blocking conduction of the myocardial action potential and inducing a “depolarized” arrest. However, an inward non-inactivating sodium “window” current occurs at these higher membrane potentials [5,6]. This condition can lead to intracellular sodium loading and calcium overload of the myocyte, resulting in contracture and cell death [7].

METHODS Surgical protocol Wistar male rats (250-350 g) were anesthetized by intraperitoneal injection of sodium thiopental (150 mg/kg). The protocol design in this study was intended to recreate the heart situation after aortic clamp release and right before heart reperfusion. The animals underwent tracheostomy and were mecha-

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nically ventilated (Minivent, Harvard Apparatus, Holliston, MA, USA). The chest was opened with a median sternotomy, the right carotid artery was catheterized, and the transverse aortic arch was isolated between the brachiocephalic artery and the left carotid artery. The transverse arch was tied, and cardioplegic solution was injected at an infusion rate of 5 mL/ min. The total dose for arresting the heart was recorded. Three different cardioplegic solutions were evaluated. The heart was excised and kept at 4oC for 4 hours, simulating the period of arrest for a transplant or a long period of aortic cross-clamp time. At the end of this period, the heart was snap-frozen in liquid nitrogen. A sample tissue of each group was evaluated with hematoxylin and eosin (HE) staining for gross assessment of the cell anatomy. All procedures were performed in accordance with the “Guide for the Care and Use of Laboratory Animals” published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996) and the Brazilian Council in Animal Experimentation (COBEA).

1% sodium deoxycholate, and 0.1% SDS. The homogenized tissue was centrifugated at 10,000 × g for 40 minutes at 4oC. The supernatant was used for ATP assessment. Myocardial ATP levels were assessed with the ENLITEN ATP assay system (Promega, Madison, WI, USA) and a Glomax 20/20 (Promega) for bioluminescence quantification, according to the manufacturer’s instructions. The ATP level was measured relative to ATP standards provided by the manufacturer. The caspase 3 activity (in relative units of activity) was assessed with the Caspase-Glo 3 Assay (Promega), according to the manufacturer’s instructions. Determination of cytotoxicity L929 cells (Genetech Inc. South San Francisco, CA, USA) were incubated at 37oC under an atmosphere of 5% CO2. Cardioplegic solutions were added to the cultured cells at progressive dilutions, and the cells were evaluated 24 hours later. The cell viability was assessed with the MTT (dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric method. Readings were performed at a wavelength of 550 nm [14].

Cardioplegic solutions The compositions of the tested cardioplegic solutions are shown in Table 1. The G/A solution (Braile Biomédica, São José do Rio Preto, Brazil) was diluted to 1% before delivery to the heart.

Statistical analysis All values were expressed as the mean ± standard deviation (SD). Variables were tested for normal distribution. One-way analysis of variance (ANOVA) or Kruskal-Wallis test was applied where appropriate. Differences with a P-value < 0.05 were considered statistically significant. All graphs and statistical analyses were performed with the GraphPad Prism version 6 software package for the Mac OS X (GraphPad Software, La Jolla, CA, USA).

Determination of the myocardial ATP and caspase 3 activity levels Myocardial tissue was removed from the liquid nitrogen, kept in the same proportion of extraction buffer, and homogenized with 25 mM Tris-HCL, 150 mM NaCl, 1% NP-40,

Table 1. Compositions of the tested cardioplegic solutions. Components Na+ K+ Mg2+ Ca2+ ClHistidine Tryptophan Glutamate Aspartate Mannitol Cromakalin Lidocaine 2,3-Butanedione Phosphoric acid pH (at 18oC)

HTK solution 15 10 4 0.015 50 198 2 __ __ 30 __ __ __ __ 7.10

LIRM solution 15 __ 4 0.015 30 __ __ __ __ __ 0.001 100 30 1.4 8.65

All concentrations are in mmol/L

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G/A (stock solution) __ 75 4 __ 34 __ __ 30 30 __ __ __ __ __ 6.90

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ATP myocardial content and caspase 3 activity levels The ATP myocardial content after 4 hours of cold storage was higher in the HTK solution group, with no differences between the LIRM and G/A groups (Figure 2A). The caspase 3 activity was higher in the G/A group compared to that of the LIRM and HTK groups, whereas the LIRM group showed higher caspase activity compared to the HTK group (Figure 2B).

RESULTS The animals showed comparable weights. Compared to the HTK and G/A solutions, less volume of LIRM solution was needed to achieve cardiac arrest (P=0.008) (Table 2). Histological findings The HE plates of the three cardioplegic solutions showed similar findings, with no gross disruption of the cell architecture or edema after 4 hours of cold preservation (Figure 1).

Cell viability None of the solutions showed cytotoxicity after contact with L929 cells for 24 hours (Figure 3).

Table 2. Animal weights and cardioplegic solution volumes required for total cessation of heart activity Solution Weight (mg) Dose for heart activity cessation (mL)

HTK (n = 5) 314.4 ± 72.5 15.8 ± 8.5

LIRM (n = 5) 306.2 ± 69.8 2.6 ± 2.5 *

G/A (n = 5) 310.2 ± 81.3 15.8 ± 4.1

P-value 0.983 0.008

* Compared to HTK and G/A solutions by one-way ANOVA

Fig. 1 - Representative left ventricle tissue sections stained with hematoxylin and eosin, showing similar findings of cell preservation in all three groups: (A) HTK, (B) LIRM, and (C) A/G solutions

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B Fig. 2 - The ATP myocardial content was higher in the HTK group compared to the other groups (A). Comparison of caspase 3 activity after 4 hours of cold storage (B). All values are expressed as the means; bars indicate standard error of the mean. Differences were assessed by one-way ANOVA. n=5 animals per group

the G/A group. Peculiarly, the caspase 3 activity showed an intermediate activity with the LIRM solution compared to the two other solutions. None of the solutions demonstrated cytotoxicity in cell culture, a finding that is not often reported in the literature regarding cardioplegic solutions [15,16]. Our findings confirm the effectiveness of HTK solution as an organ preservation solution, as demonstrated by ATP conservation. Another important finding was the lower activity of caspase 3 with HTK solution, which is not often reported [17]. The LIRM solution showed a beneficial effect on caspase 3 activity and a very effective ability to arrest the heart without potassium. The ideal cardioplegic solution, which has yet to be determined, should allow a rapid and effective induction of diastolic arrest, should minimize ischemia/reperfusion injury, and should have no deleterious effects on other organs [18]. The rapid and effective induction of cardiac arrest may minimize myocardial ATP depletion and contribute to the protective effects during the reperfusion period [18-20]. In the present study, the LIRM solution displayed a pronounced capacity to promote cardiac arrest compared to the other two solutions. However, the myocardial ATP content was very similar when the LIRM and G/A solutions were used. Regardless of the cause, the caspase 3 activity of the LIRM solution was lower than that of the G/A solution, which might represent an improvement during the reperfusion period. An analysis of the details of this concept is beyond of the scope of the current study. The HTK solution effectively reduced the energy requirements, as observed in this and previous studies [21]. Howe-

Fig. 3 - Cell viability of L929 cells after incubation with cardioplegic solution for 24 hours. None of the solutions showed cytotoxicity during the observation period

DISCUSSION In this study, we evaluated the effect of three different cardioplegic solutions on myocardial ATP content and caspase 3 activity after 4 hours of cold conservation. We also evaluated cell cytotoxicity after 24 hours of exposure to the cardioplegic solutions. The ATP myocardial content was higher in the HTK group compared to the G/A and LIRM groups. The caspase 3 activity was the lowest in the HTK and highest in

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ver, other reports have shown an inability of HTK solution to reduce endothelial dysfunction after long periods of cold storage [22]. The LIRM solution contains cromakalin, which has beneficial effects on endothelial function and coronary vasodilation. Nevertheless, the beneficial effects of this agent were not tested in the present study design [23]. To induce a pharmacologic arrest, the arresting agents of a cardioplegic solution must interact with some targets involved in excitation-contraction coupling. This effect can be reached by inhibiting the myocardial action potential propagation and/or inhibiting calcium activation of the myofilaments. The LIRM solution has components to induce cardiac arrest by both of these mechanisms. The LIRM solution contains three different agents (cromakalin, 2,3-butanedione, and lidocaine) at very low concentrations to induce cardioplegic arrest without hyperkalemia. All three components were added to the initial formula for sum effect and to avoid any deleterious effects of the higher concentration of one isolated component. The other solutions tested in this report induce cardiac arrest by different mechanisms. The G/A solution induces cardiac arrest by inhibiting the action potential by hyperkalemia, leading to depolarization of the cell membrane. The HTK solution does the same, inhibiting the myofilament action by providing a very low calcium concentration. Although universally used, the strategy of depolarized arrest with hyperkalemia has distinct disadvantages. In particular, cellular ionic currents are maintained during the ischemia/arrested period, which can lead to adverse effects [18,24]. Hyperkalemia shifts the membrane potential of the myocytes to a range between -65 and -40 mV. At this voltage, not all of the sodium channels are inactivated. Sodium influx by non-inactivated sodium channels [5,6] can lead to the activation of the sodium-hydrogen exchanger and intracellular acidosis [7,25,26]. Consequently, acidosis and ischemia lead to inhibition of the sodium/potassium-ATPase [26] and further increase the intracellular sodium. Sodium overload causes the sodium/calcium exchanger channel to act in reverse mode, increasing the calcium loading of the myocyte and leading to contracture and cell death [7]. One potential disadvantage of the LIRM solution compared to the HTK and G/A solutions is the inexistence of components that might supply the Krebs cycle, such as tryptophan in the HTK solution or aspartate and glutamate in the G/A solution. The absence such components might be responsible for the lower myocardial ATP content observed with the LIRM solution. The addition of some precursors of the Krebs cycle to the LIRM solution might improve the energy maintenance during cold storage, as assessed by the myocardial ATP content.

nimum, and contractility indexes. Conclusions were limited to the period before reperfusion, but we were able to show a higher myocardial ATP content with the HTK solution, different caspase activities in all three groups, and higher effectiveness of the LIRM solution in achieving cardiac arrest. CONCLUSIONS The HTK solution was more effective in promoting higher levels of myocardial ATP content compared to the two other solutions. The LIRM solution was very effective in promoting cardiac arrest and reducing caspase 3 activity compared to the A/G solution. These preliminary data concerning the use of different pharmacological agents for cardiac arrest are promising. In the future, cardioplegic solutions containing Krebs cycle substrates, such as tryptophan and histidine, might be considered. Authors’ roles & responsibilities KR Implementation, writing and discussion HRPC Implementation, writing and discussion FL Execution discussion AGT Writing and discussion KASV Design, execution, writing and discussion PPMO Discussion and manuscript review LMSF Discussion and manuscript review ESBOS Discussion and writing OP Design, writing, analysis

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Study limitations We did not evaluate hemodynamic data, such as left ventricle systolic and diastolic pressures, dP/dt maximun and mi-

6. Attwell D, Cohen I, Eisner D, Ohba M, Ojeda C. The steady state TTX-sensitive ("window") sodium current in cardiac Purkinje fibres. Pflugers Archi.1979;379(2):137-42.

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7. Satoh H, Hayashi H, Katoh H, Terada H, Kobayashi A. Na+/ H+ and Na+/Ca2+ exchange in regulation of [Na+]i and [Ca2+] i during metabolic inhibition. Am J Physiol. 1995;268(3 Pt 2):H1239-48.

17. Viana FF, Shi WY, Hayward PA, Larobina ME, Liskaser F, Matalanis G. Custodiol versus blood cardioplegia in complex cardiac operations: An Australian experience. Eur J Cardiothorac Surg. 2013; 43(3):526-31.

8. Dunne MJ, Aspinall RJ, Petersen OH. The effects of cromakalim on ATP-sensitive potassium channels in insulin-secreting cells. Br J Pharmacol. 1990;99(1):169-75.

18. Chambers DJ, Fallouh HB. Cardioplegia and cardiac surgery: pharmacological arrest and cardioprotection during global ischemia and reperfusion. Pharmacol Ther. 2010;127(1):41-52.

9. Rudd DM, Dobson GP. Eight hours of cold static storage with adenosine and lidocaine (Adenocaine) heart preservation solutions: toward therapeutic suspended animation. J Thorac Cardiovasc Surg. 2011;142(6):1552-61.

19. Silveira Filho LM, Petrucci O Jr, Carmo MR, Oliveira PP, Vilarinho KA, Vieira RW, et al. Trimetazidine as cardioplegia addictive without pre-treatment does not improve myocardial protection: study in a swine working heart model. Rev Bras Cir Cardiovasc. 2008;23(2):224-34.

10. Stringham JC, Paulsen KL, Southard JH, Fields BL, Belzer FO. Improved myocardial ischemic tolerance by contractile inhibition with 2,3-butanedione monoxime. Ann Thorac Surg. 1992;54(5):852-9.

20. Lima-Oliveira APM, Azeredo-Oliveira MTV, Taboga SR, Godoy MF, Braile DM. Cardioplegia utilizando baixo volume de agentes cardioplégicos: Estudo morfológico em coração isolado de coelhos. Rev Bras Cir Cardiovasc. 2003;18:227-34.

11. Peart JN, Headrick JP. Clinical cardioprotection and the value of conditioning responses. Am J Physiol Heart Circ Physiol. 2009;296(6):H1705-20.

21. Hachida M, Ookado A, Nonoyama M, Koyanagi H. Effect of HTK solution for myocardial preservation. J Cardiovasc Surg (Torino). 1996;37(3):269-74.

12. Stringham JC, Paulsen KL, Southard JH, Mentzer RM Jr, Belzer FO. Forty-hour preservation of the rabbit heart: optimal osmolarity, [Mg2+], and pH of a modified UW solution. Ann Thorac Surg. 1994;58(1):7-13.

22. Radovits T, Lin LN, Zotkina J, Koch A, Rauen U, Köhler G, et al. Endothelial dysfunction after long-term cold storage in HTK organ preservation solutions: effects of iron chelators and N-alphaacetyl-L-histidine. J Heart Lung Transplant. 2008;27(2):208-16.

13. Wei L, Wu RB, Yang CM, Zheng SY, Yu XY. Cardioprotective effect of a hemoglobin-based oxygen carrier on cold ischemia/ reperfusion injury. Cardiology. 2011;120(2):73-83.

23. Perrault LP, Menasché P. Preconditioning: can nature’s shield be raised against surgical ischemic-reperfusion injury? Ann Thorac Surg. 1999;68(5):1988-94.

14. Stockert JC, Blázquez-Castro A, Cañete M, Horobin RW, Villanueva A. MTT assay for cell viability: Intracellular localization of the formazan product is in lipid droplets. Acta Histochem. 2012;114(8):785-96.

24. Oliveira MAB, Godoy MF, Braile DM, Lima-Oliveira APM. Solução cardioplégica polarizante: estado da arte. Rev Bras Cir Cardiovasc. 2005;20(1):69-74.

1 5 . P r z y g o d z k i T, L a p s h i n a E , Z a v o d n i k I , S o k a l A , Bryszewska M. 2,3-Butanedione monoxime does not protect cardiomyocytes under oxidative stress. Cell Biochem Funct. 2006;24(5):413-8.

25. Pike MM, Luo CS, Clark MD, Kirk KA, Kitakaze M, Madden MC, et al. NMR measurements of Na+ and cellular energy in ischemic rat heart: role of Na(+)-H+ exchange. Am J Physiol. 1993;265(6 Pt 2):H2017-26.

16. Drescher C, Diestel A, Wollersheim S, Berger F, Schmitt KR. How does hypothermia protect cardiomyocytes during cardioplegic ischemia? Eur J Cardiothorac Surg. 2011;40(2):352-9.

26. Lahorra JA, Torchiana DF, Tolis G Jr, Bashour CA, Hahn C, Titus JS, et al. Rapid cooling contracture with cold cardioplegia. Ann Thorac Surg. 1997;63(5):1353-60.

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Rodrigues AJ, et al. - On-pump versus off-pump coronary artery bypass graft REVIEW ARTICLE surgery. What do the evidences show?

On-pump versus off-pump coronary artery bypass graft surgery. What do the evidences show? Revascularização cirúrgica do miocárdio com versus sem circulação extracorpórea. O que mostram as evidências?

Alfredo José Rodrigues1, MD; Paulo Roberto Barbosa Évora1, MD; Paulo Victor Alves Tubino1

DOI: 10.5935/1678-9741.20130086

RBCCV 44205-1508

Abstract The main purpose of the off-pump coronary artery bypass surgery is to reduce morbidity and mortality due cardiopulmonary bypass. However, even though many studies have shown that off-pump coronary artery bypass is feasible and provides hospital morbidity and mortality similar to the on-pump coronary artery bypass graft surgery, probably better in some aspects, its long-term results have been questioned, since some trials have shown reduced survival with off-pump coronary artery bypass. It is likely that incomplete revascularization and/or poor graft patency with off-pump coronary artery bypass probably are responsible for such unfavorable outcome.

circulação extracorpórea visa à diminuição da morbimortalidade decorrente dos potenciais efeitos deletérios da circulação extracorpórea. Todavia, embora a maioria dos estudos demonstre que a revascularização sem circulação extracorpórea é factível e forneça resultados similares à operação com circulação extracorpórea, no que se refere à morbimortalidade hospitalar, e pode mesmo diminuir a incidência de alguns eventos, sua eficácia a médio e longo prazo tem sido questionada. Alguns estudos demonstram menor sobrevida em pacientes submetidos à revascularização do miocárdio sem circulação extracorpórea, levantando a hipótese de que a revascularização incompleta e/ou a pior evolução dos enxertos realizados na operação sem circulação extracorpórea em comparação à operação com circulação extracorpórea, observadas em alguns estudos, seriam responsáveis por essa evolução desfavorável.

Descriptors: Myocardial revascularization. Coronary artery bypass. Coronary artery bypass, off-pump. Evidence-based medicine.

Descritores: Revascularização miocárdica. Ponte de artéria coronária. Ponte de artéria coronária sem circulação extracorpórea. Medicina baseada em evidências.

Resumo A proposta da revascularização do miocárdio sem emprego da

Ribeirão Preto Medical School of the University of São Paulo (FMRPUSP), Ribeirão Preto, SP, Brazil

Av. Bandeirantes, 3900 - Monte Alegre - Ribeirão Preto, SP, Brasil Zip code: 14049-900 E-mail: alfredo@fmrp.usp.br

1

This study was carried out at Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil

There was no financial support.

Correspondence address: Alfredo José Rodrigues Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Article received on August 26th, 2013 Article accepted on September 15th, 2013

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assess the available evidence and know how to employ them in clinical practice.

Abbreviations , acronyms & symbols CPB Cardiopulmonary bypass CVA Cerobrovascular accidents PCT Prospective clinical trials EuroSCORE European System for Cardiac Operative Risk Evaluation

Hospital morbidity and mortality The first investigations were retrospective analyzes, especially for large databases, and small observational studies. Most of these studies showed that OPCAB decreased hospital morbidity and mortality [13-15] or had mortality and morbidity similar to CABG with CPB [16]. Thus, the results of prospective clinical trials with random allocation (PCT) began to appear, initially with small samples and low-risk patients. One of the first of these studies was of Gerola et al. [17], which showed that although the hospital mortality in patients undergoing surgery without CPB was lower than that observed in patients undergoing surgery with CPB, the difference was not significant, as well as the differences observed in the incidence of postoperative complications. In 2009, the results of the first PCT with extensive sampling performed by the research group of Veteran Affairs, North America, the ROOBY Study Group [18], were published. In this study, 2023 patients were randomly assigned to undergo CABG with or without CPB. The results showed that OPCAB provided similar results to surgery with CPB with respect to hospital mortality. In 2012, the results with 30 days of ECP performed by CORONARY group [19], a multicenter, multinational study that enrolled more than 4,700 patients have been published. This study showed that despite the hospital mortality is similar between surgery with and without CPB, OPCAB significantly reduced the need for transfusion and reoperation for bleeding, in addition to the incidence of acute renal failure and respiratory complications. Even with regard to hospital mortality, results of recent meta-analyzes [20,21] have shown that apparently the general population of coronary mortality in patients operated with and without cardiopulmonary is similar.

INTRODUCTION It is undisputed that the advent of cardiopulmonary bypass (CPB) favors the development of cardiac surgery. Despite the continuous evolution, it is undeniable that the CPB has harm potential as a result of pathophysiological processes that are inherent and can result in tissue damage and organ dysfunction [1]. Moreover, there is considerable risk of cerebrovascular accidents (CVA) in cardiovascular surgeries, partly resulting from events related to CPB [2,3]. Vasilii Kolesov [4,5] has been considered one of the pioneers of coronary artery bypass grafting and published in 1967 their clinical series using the internal thoracic artery anastomosed to the coronary arteries without use of CPB [6]. However, his option for OPCAB was not due to lack of apparatus for its performance, but by recognizing its deleterious effects [7], especially in the early stage of clinical use. In one of his articles he had written: “Although cardiopulmonary bypass is safe and reliable ..., the overall inflammatory response after cardiopulmonary bypass is too intense to justify its use for CABG� [4]. Although the use of CPB for performing the CABG has gained popularity, driven by the improvement of CPB devices and the publication of the excellent results of revascularization with its use [8,9], some surgeons continued to defend that revascularization surgery could offer even better results without the use of CPB, decreasing the morbidity and mortality associated with CPB [10-12]. As the interest in the use of revascularization without CPB was gradually increasing, especially meeting the challenges posed by the progressive evolution of percutaneous procedures, several issues have emerged:

Stroke The incidence of stroke after cardiac surgery ranges from 3% to 9%, and its effect on postoperative morbidity is significant and can increase mortality from 4% to 19% [3]. Three different mechanisms can cause perioperative stroke: cerebral perfusion deficit, embolic events, and the inflammatory response, which in turn can also magnify the effects of other mechanisms [2]. Thus, as part of the stroke is closely connected to the CPB, it seems logical that its exclusion may decrease the incidence of perioperative stroke. Recent meta-analyzes that included several PCT [2023] and analysis of databases [24] shows that OPCAB is associated with lower risk of stroke. But in the last two large prospective trials, ROOBY [18] and the CORONARY groups [19], the incidence of stroke were similar in both surgeries, both in the first month as after one year [25].

a) Is the CABG without the use of CPB safe? b) Does it really reduce hospital morbidity and mortality? c) Are the results comparable to those of surgery with CPB, especially with regard to security, survival and quality of grafts? d) Is it possible to perform the full revascularization using the method? e) It the method reproducible? Thus, the search for answers to these questions led to the development of several studies, progressively building the body of evidence. It is necessary for surgeons to critically

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The greater statistical power of the meta-analyzes to detect differences may explain this discrepancy in the results, although the meta-analysis may be influenced by selection bias in clinical trials. In recent meta-analysis filtered by the COCHRANE [26] it was observed a lower risk of stroke in OPCAB when considering all selected studies, but when the analysis was restricted to studies with low risk of bias, the difference was not significant. Also, different rules and protocols for the detection of postoperative stroke may also explain the differences between studies. Moreover, probably the most strokes that occur in coronary artery bypass operations are not directly related to the CPB, but the manipulation of atherosclerotic aorta, especially its clamping. Thus, in off-pump surgeries the manipulation of the ascending aorta for confection of proximal anastomoses is certainly one of the predominant causes of embolic stroke. Thus, some argue that on-pump CABG surgery, but without aortic clamping and/or performing proximal anastomoses of vascular grafts, with the heart beating and/or under fibrillation, may result in a decrease in the incidence of stroke. We should know that the cannulation of the aorta and the femoral vessels and the turbulent flow caused by arterial cannulas may also result in embolization of atherosclerotic material.

the ROOBY study is due to important differences between the two studies. The CORONARY study recruited more than twice as many patients in general with more comorbidities, and only allowed the participation of surgeons with experience in OPCAB, which resulted in lower conversion rate (7.9% vs. 12.4%) and need for further revascularization at 30 days and 1 year (0.6 % vs. 3.5%). Meta-analyzes and systematic reviews of recently published prospective studies [26,30,31] show a higher risk of late mortality for patients undergoing surgery without CPB. It is speculated that this trend may be due to an increased probability of incomplete revascularization in offpump CABG. Complete revascularization Given the potential prognostic implications of incomplete myocardial revascularization [32,33], this has been an important concern in studies comparing CABG with and without CPB, but whose results have also shown contradictory. Several authors have observed that the number of distal anastomoses is significantly lower and/or higher occlusion rate of grafts in patients undergoing OPCAB [18,22,26,28,34-36], others found no significant differences in the evolution of grafts [25,37-40] or quality of the anastomosis [41]. Currently, it is considered that the “index of complete revascularization� (number of grafts divided by the number of grafts needed) is more important than the absolute number of distal anastomoses. Magee et al. [42] assessing the surgical and angiographic data prospectively collected from 945 patients included in a database noted that although the number of grafts in off-pump CABG was lower, the rate of complete revascularization was generally similar between patients undergoing surgery with and without CPB. However, we found that surgeons who performed OPCAB in less than 25% of patients had complete revascularization rate significantly lower.

Survival Although many studies show that early mortality of OPCAB is comparable to that obtained with the use of CPB, but lower in some aspects, the results related to medium and long term are controversial. By assessing the follow-up between six and eight years of 401 patients who participated in two PCT (BHACAS I and II) Angeli et al. [27] observed that survival free of cardiac events, including death, was similar to surgeries with and without CPB. A similar result was observed in the MASS III [28] study after five years of follow-up. Puskas et al. [29] observed a trend toward greater survival in patients undergoing surgery without CPB which reached significance in the fifth year of follow-up, but no significant difference in the seventh year. Studies of ROOBY and CORONARY groups provided divergent results. In the ROOBY [18] study group, after one year of follow-up the authors observed significantly higher incidence of composite outcomes, including mortality from cardiac causes in patients undergoing surgery with CPB, although when we considered all-cause mortality the difference was not significant. The results with one year follow-up from the CORONARY study group [25] showed no significant difference between patients undergoing surgery with and without CPB in relation to primary compound outcomes, the rate of new coronary revascularization, quality of life or neurocognitive function. The authors comment that this divergence of results from

On- and off-pump CABG surgery in high-risk patients Considering that the ability to reduce the risk of occurrence of a specific outcome provided by a given treatment may keep constant, when treatment is employed in population with higher risk of this outcome, so the outcome has a higher incidence in this group, the lower the required number of patients to demonstrate that the benefit of treatment [43]. Thus, investigations in order to compare the results of revascularization with and without cardiopulmonary bypass in high-risk groups has emerged, although there are still few ECP and usually with relatively small samples. Two recent PCT [44,45], in which the operation with or without cardiopulmonary bypass were compared in patients aged over 75 years showed no significant difference in hospital mortality and survival at 6 months and 1 year.

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Cavallaro et al. [23], when assessing the results of over 80,000 revascularization with and without cardiopulmonary bypass in a group of patients considered of high risk ( ≥ 85 years, COPD, renal failure, peripheral artery disease and aortic atherosclerosis), observed that the only event with significantly different incidence was stroke, lower in the subgroup of patients aged ≥ 80 years and/or patients with peripheral artery disease or aortic atherosclerosis. For the patients considered of high risk by EuroSCORE (score>5), Moller et al. [46] found no significant difference in the incidence of major cardiac events, but noted a higher allcause mortality after three years in the off-pump group. Lemma et al. [47] in a multicenter PCT (on-off study) reported a lower incidence of composite primary outcomes, including hospital mortality in patients operated without CPB, although the difference in the incidence of each event were not considered individually significant. Marui et al. [24], when assessing a multicenter registry in Japan (CREDO-Kyoto), observed that in the substrate of high risk patients (EuroSCORE ≥ 6) the OPCAB was associated with lower risk of short- and long-term stroke. However, no survival benefit was observed regardless of the level of preoperative risk. In patients with left ventricular dysfunction both prospective trials, with [48] and without random allocation [49] and meta-analyzes [35] or retrospective analyzes of large databases with risk adjustments [50] have shown less morbidity in patients operated without CPB, the same occurring in diabetic patients [51,52].

reduction of 3% to 1.8% a sample of 5,400 patients (G* Power 3.1.5 software, Heinrich Heine University Düsseldorf). Thus, this difficulty can be called “Pollyanna effect”, or that is, there will always be difficulty in demonstrating the possibility of improvement when everything is doing well. The meta-analysis, although increasing the statistical power by aggregating samples of various studies, are also not exempt from be biased due to the use of inappropriate methodology for the selection of included trials and/or errors in the statistical analysis. Moreover, although there are sophisticated statistical methods aimed at verifying the absence of random assignment (propensity score) in observational studies, these analyzes still carry residual risk of bias caused by not measured “confounding factors”, and may underestimate possible deleterious effects with the treatment [26,53]. In a recent filtered systematic review performed by Cochrane Database of Systematic Reviews [26], the authors warned that from the 86 trials included in the review, only 10 had low risk of bias, 26 studies had a high risk of bias observation (“not blinded”) despite being considered properly “randomized”, and in the other 50 studies, the risk of allocation bias was undefined or had the risk of high or indefinite observation bias. In this review, which did not include the results of a year from the CORONARY study group [25], it was found that when compared to surgery with CPB the OPCAB increased the risk of death from any cause, provided a smaller number of distal anastomoses. And although the risk of stroke was lower in the off-pump surgery, when we assessed only the data from the trials with low risk of bias the difference disappeared. Importantly, not only in medical practice the best evidence should be considered, but the physician has an obligation to assess each particular clinical situation, considering also the values and expectations of the patient, as well as his clinical experience [53]. It should also be alert to the fact that in general the events that compose the “composite outcomes” do not have all the same “value”, especially for patients and they should be considered separately. We should consider that although certain treatment may not be beneficial to the general population, it may be in certain subgroups, and the opposite is also possible, and that the potential harm of treatment should also be considered in assessing the risk/ benefit.

Critical analysis of outcomes Although prospective clinical trials with random allocation are at the top of the hierarchical pyramid to provide evidence, such studies are not free of systematic error (bias) caused by inadequately designed and/or performed projects. Inadequate sample size, selection bias and/or assignment and/or assessment, co-intervention, follow-up loss, lack of external validation and analysis of compound events should be considered in the critical analysis of the studies, and often explain the divergent results. We must also consider that even properly designed and performed projects may produce results that do not reflect reality, the so-called “random error” or “type I error or a” or whose probability of occurrence is given by “P value” in statistical tests [53]. Even though it seems counterintuitive when we do not observe significant differences in hospital mortality when it stops using known method that imposes potential damage, such as cardiopulmonary bypass, for example, it should be remembered that the sample size required to observe significant differences in rare events is high. Using the chisquare two-tailed test with correction for continuity (Fisher’s exact test) with a "P" value of 0.05 and 80% power to detect a 40% reduction in mortality rate, for example, of 2% to 1.2%, a sample of more than 8,000 patients would be required, and

CONCLUSION We can say that, given the available evidence, CABG with CPB remains the standard operation, but that CABG without CPB is feasible with a similar operation with hospital morbidity and mortality similar to on-pump surgery, but with potential to reduce morbidity and mortality in hospital subgroups at higher risk. However, further studies are needed

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to assess its use in these subgroups, because although OPCAB may provide benefits, it also has the potential to cause harm, like any treatment. Considering that the trend toward shorter survival with OPCAB observed in some studies may be related to incomplete revascularization and/or higher rates of grafts with unsatisfactory progress, which seems more likely with less experienced surgeons with the technique, it is prudent to consider that OPCAB is not a surgery that should be performed routinely by any cardiac surgeon, but due to its beneficial potential in specific situations, every surgeon should enable himself to perform it through proper training and use of specific available technology.

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Authors' roles & responsibilities AJR PRB PVA

Author, review and drafting Author, review and drafting Coauthor, bibliographic survey, formatting, writing

12. Trapp WG, Bisarya R. Placement of coronary artery bypass graft without pump oxygenator. Ann Thorac Surg. 1975;19(1):1-9. 13. Li Z, Yeo KK, Parker JP, Mahendra G, Young JN, Amsterdam EA. Off-pump coronary artery bypass graft surgery in California, 2003 to 2005. Am Heart J. 2008;156(6):1095-102. 14. Mack MJ, Pfister A, Bachand D, Emery R, Magee MJ, Connolly M, et al. Comparison of coronary bypass surgery with and without cardiopulmonary bypass in patients with multivessel disease. J Thorac Cardiovasc Surg. 2004;127(1):167-73.

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Jesus DF & Marques PF - ARTICLE Nursing assistance at the hospital discharge after REVIEW cardiac surgery: integrative review

Nursing assistance at the hospital discharge after cardiac surgery: integrative review Assistência de enfermagem na alta hospitalar em pós-operatório de cirurgia cardíaca: revisão integrativa

Daniela Fraga de Jesus1,2; Patrícia Figueiredo Marques1, MD

DOI: 10.5935/1678-9741.20130087

RBCCV 44205-1509

Abstract

Resumo O estudo objetivou analisar evidências disponíveis na literatura sobre a assistência de enfermagem na alta hospitalar em pós-operatório de cirurgia cardíaca. Os dados foram coletados das bases eletrônicas LILACS, SciELO, MEDLINE, através dos DeCS cirurgia torácica, alta hospitalar, cuidados de enfermagem, no período de 2001 a 2011. Foram selecionados dez artigos que revelaram a necessidade de desenvolver um plano de alta de enfermagem com foco na prevenção das complicações e no enfrentamento das limitações físicas decorrentes da cirurgia cardíaca. Destarte, a alta hospitalar deve ser pensada desde o momento da admissão, com ações de cuidado planejadas envolvendo paciente e familiar.

Descriptors: Cardiovascular surgical procedures. Nursing

Descritores: Procedimentos cirúrgicos cardiovasculares. Cuidados de enfermagem. Alta do paciente.

INTRODUCTION

occurrence [4]. Because of their several causes and complexity level, cardiac pathologies must have their course urgently interrupted with clinical and/or surgical treatment [5]. Since the treatment is complex, the institution must offer specialized material and human resources as well as a multidisciplinary team with technical-scientific expertise and skills to carry on the daily activities and the ability to see the individual as a whole [6]. A multidisciplinary team should consist of clinicians, cardiologists, electrophysiologists, cardiac surgeons, vascular surgeons, anesthesiologists,

The study aimed to assess evidence available in the literature on nursing care during hospital discharge following cardiac surgery. Data were collected from the LILACS, SCIELO, and MEDLINE electronic databases, via the Decs: thoracic surgery, hospital, and nursing care, in the period 2001-2011. Ten articles were selected, which showed the need to develop a plan for nursing discharge focused on preventing complications and coping with physical limitations resulting from heart surgery. Thus, the discharge should be considered from the time of admission, with carefully planned actions involving patient and family.

care. Patient discharge.

Cardiovascular diseases are the main cause of morbimortality of the Brazilian population [1]. The diseases of the circulatory system with high level of morbimortality are: heart ischemic disease, cerebrovascular diseases, heart failure, and valvulopathies, especially of rheumatic origins, among others [2,3]. There is no single cause for those diseases, but there are several risk factors which increase the probability of their

Universidade Federal do Recôncavo da Bahia (UFRB), Cruz das Almas, BA, Brazil. 2 Universidade São Camilo, São Paulo, SP, Brazil.

Correspondence address: Daniela Fraga de Jesus Av. Carlos Amaral, 1015 – Cajueiro – Santo Antônio de Jesus, BA, Brazil – Zip code: 44570-000 E-mail: dany_fj_@hotmail.com

1

Work carried out at Universidade Federal do Recôncavo da Bahia (UFRB), Cruz das Almas, BA, Brazil.

Article received on April 7th, 2013 Article accepted on October 7th, 2013

No financial support.

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Jesus DF & Marques PF - Nursing assistance at the hospital discharge after cardiac surgery: integrative review

[19]. Thus, hospital discharge should be handled by an interdisciplinary team, mediated by the nurse, who will be the link between the professionals so that the specific needs of each patient are met [20]. Therefore, and to serve as a basis for the job of the nursing team, the present study set out to analyze the evidence available in the literature about nursing assistance at hospital discharge after cardiac surgery.

Abbreviations, acronyms & symbols DeCS Descriptors LILACS Literatura Latino Americana em Ciências de Saúde MEDLINE Medical Literature Analysis and Retrieval System Online SciELO Scientific Electronic Library Online

cardiologists, nutritionists, physiotherapists, psychologists, and nursing staff [7]. Among the professionals in the multidisciplinary team, the nurse and the psychologist are extremely important because patients usually present symptoms such as anxiety, depression, negative thoughts about the future, and lack of confidence, especially in the postoperative period [8]. The psychologist seeks to reduce feelings that may interfere with the patient’s recovery as well as to prepare him throughout his hospitalization, with the goal of providing trust and peacefulness so that the patient can avoid feeling beaten and tortured [9]. In this context, the role of a nursing team is extremely important, once they assist the patient uninterruptedly during the hours following surgery and are responsible for setting up the unit as well as providing human and material resources [10]. Besides having technical and scientific knowledge, the team is in charge of caring, controlling, and observing the patient by taking into account the complexity of the surgery in addition to the vitality of the organ system involved [2,11]. For this reason, the nurse should organize and plan the assistance based on the methodological steps of the nursing process in order to intervene in accordance with the individual needs of the patient [12]. Hence, nursing practice should be guided by the scientific method as it enables the nurse to identify and meet the needs of the assisted person, through the patient’s medical history, nursing diagnosis, planning, and correct implementation and evaluation. However, to meet the needs of patients, the nurse also needs skills, cognitive competence, and constructive technical, organizational and interpersonal relationships, both objectively and subjectively [13]. Despite the intensive care of the nursing team, the occurrence of complications after cardiac surgery is very common and is one of the main causes of morbidity and mortality in the postoperative period [14]. Consequently, nursing care has to be planned systematically so that after discharge the patient does not fear or feel insecure about the new lifestyle, the limitations resulting from the procedure, changes in diet, and other relevant orientations according to the needs of the patient [15-17]. Guidance on discharge is commonly given mechanically and briefly, not taking into consideration the patient’s condition and needs [18]. That happens because nurses face difficulties in communicating with physicians. They are not informed about discharge, only becoming aware of it when the patient is leaving or after they have left the hospital

METHODS This is an integrative review whose methodological strategy is justified because it summarizes knowledge and incorporates applicable results of practical and meaningful studies [21,22]. In the process of making this integrative review, some operationalization patterns that contributed to the development of the study were followed: (1) the hypothesis was formulated and the problem was identified ; (2) inclusion and exclusion criteria for the selection of samples were established; (3) the analysis of relevant information extracted from the studies was done; (4) the studies included in the review were evaluated; (5) the results were interpreted; and (6) the review was presented, synthesizing the resulting knowledge [23,24]. The study was guided by the following question: what is the available evidence in literature about nursing assistance at hospital discharge after cardiac surgery? The literature review was based on the LILACS (Literatura Latino Americana em Ciências de Saúde), SCIELO (Scientific Electronic Library Online), and MEDILINE (Medical Literature Analysis and Retrieval System Online) electronic databases. The descriptors (Decs) used for Health Science were: thoracic surgery, hospital discharge, and nursing care. The criteria for sample inclusion were based on articles published in Portuguese, English, Spanish, and French, fully available, from 2001 and 2011. The articles were selected based on the analysis of their title and abstract. Those that did not address the issue anddid not meet the inclusion criteria above were excluded. Articles published twice were considered only once. The instrument used for data collection was a grid, created specifically for this study, which was completed by each chosen item with information about identity Id (P1, P2, P3, ...), journal, article title, authors/year, authors’ institution, authors’ profession, QUALIS system, and considerations/ themes. After inserting the information into the grid, the studies selected were evaluated through careful reading, during which contributions were extracted, results were interpreted, discussions were presented descriptively, and information collected for each article was summarized (Table 1).

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Table 1. Presentation of the synthesis of the articles selected for the integrative review. Journal

Authors/ Year

Article Title

Considerations/Thematic

Rev Min Enferm. [27]

Romanzini AE et al. 2010

Nursing guidelines to patients about self-care and symptoms and signs of surgical site infections after discharge of reconstructive cardiac surgery

It collects information from patients about nursing guidelines concerning self-care as well as symptoms and signs of surgical site infections after hospital discharge from a reconstructive cardiac surgery.

Rev Esc Enferm USP. [26]

Razera APR et al. 2011

The importance of communication during the recovery from post operative

Presents postoperative guidance provided by the nursing team to patients and/or families at a private institution, and the perception of these individuals about the guidance they received.

Esc Anna Nery R Enferm. [28]

Dutra CMP & Coelho MJ 2006

Implantation of mechanical mitral valve: reflections to the take care and the care of customers after the hospital discharge

It describes the participation of the nursing staff in the process of adopting new approaches related to care/daily care of clients undergoing mitral valve implant.

Rev Bras Enferm. [33]

Rocha LA et al. 2006

Nursing diagnosis in patients outgoing cardiac surgery

It identifies diagnosis and nursing interventions for planning nursing assistance to patients in the postoperative period of myocardial revascularization cardiac surgery.

Rev Esc Enferm USP. [34]

Galdeano LE et al. 2006

Nursing diagnosis in perioperative cardiac surgery

It identifies nursing diagnosis of patients in the perioperative period of cardiac surgeries and verifies its compliance by nurses.

Cogitare Enferm. [25]

Gasperi PD et al. 2006

Seeking to re-educate habits and customs: the nursing care process in the preoperative and postoperative period of cardiac surgery

It presents a report of the development of a nursing assistance practice aimed at improving the health of patients undergoing cardiac surgery, as well as their parents’, in an attempt to change their habits.

Rev Bras Cir Cardiovasc. [32]

Boaz MR et al. 2006

The importance of preventive measures in the prophylaxis of infections in patients submitted to heart transplant during the first thirty postoperative days.

It describes the occurrence of infections on patients undergoing cardiac transplant, during the first 30 days of the surgery, concerning topography and etiologic agent and it compares the incidence of infections in the postoperative period right after the cardiac transplant with preventive measures adopted to control these infections.

Rev Enferm UERJ. [29]

Pereira APS et al. 2007,

Hospital discharge; view of a nursing team

It points out that the understanding of the process of hospital discharge involves relationships, nurses’ experiences along with their beliefs, feelings, rituals, meanings, attitudes, motivations, behaviors and actions.

Rev Latino-Am. Enfermage [33]

Andrietta MP et al 2011

Hospital discharge plan to patients with congestive cardiac failure

It describes how nurses have planned discharge of patients with congestive cardiac failure because not planning the discharge adequately and not following guidance are seen as possible factors of a new hospitalization.

Crit Care Nurse. [31]

Paul S. 2008

Hospital discharge education for patients with heart failure: what really works and what is the evidence?

It presents the barriers to self-care and how nurses can help the patients to overcome these barriers through the education of patients at hospital discharge and by promoting self-care that reduces rehospitalization rates.

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Regarding ethical aspects, the authors of this study were concerned with registering the necessary information to identify the authors of the articles investigated and not altering the available information in those documents. For this reason, the material was reproduced and analyzed impartially in order to avoid bias.

surgery so they can understand it and adapt to possible changes, especially in the postoperative period [23,31]. This is a tense moment, causing emotional stress, insecurity, and fear so the nursing staff must be prepared to guide patients and their families to reduce their anxiety and to comfort them. Trust within the nurse-patient relationship should happen through a two-way communication because it builds an important foundation for the care to be carried out efficiently and effectively, and it provides understanding of the patient as a whole [26]. These complications may be of cardiovascular, pulmonary, renal, gastrointestinal, and neuropsychiatric origins. Due to the complexity of cardiac surgeries, the postoperative period is monitored by a multidisciplinary team through continuous monitoring and critical decision making and care. However, it is the nursing staff that monitors the patient full-time, providing specific care that aims at reducing complications and maintaining the balance of the organic system, through planned assistance [22]. On the other hand, one study found that nurses still develop more technical care at the bedside, devoid of greater interaction with the patient and his family [35]. Essentially, the technical model of health care is still very present in the daily routine of health professionals. In nursing, this type of care is repeated in the postoperative period, through interventions aimed at preventing complications with the surgical incision and unidirectional guidelines preparing patients to return to their homes and their daily activities. There is no systematic care involving a discharge plan or the patient. To change this reality, it is essential that the nursing staff make use of scientific knowledge and records of the multidisciplinary team to develop a discharge plan [33]. That plan must be developed from the moment the patient is admitted so as to provide greater safety and reduce the risk of complications [34]. The specific type of heart surgery should also be considered because the length of stay will vary according to the surgical procedure and the patient’s condition. In addition, it may involve the temporary or permanent suspension of some activities, altering the lifestyle of the patient. To that end, it is necessary that the family and the patient follow specific care procedures after the surgery [27]. In this context, the discharge should be carried out with the help of a psychologist working with the family and the patient, in an attempt to help the patient understand the changes and adapt to a different lifestyle by developing new skills. Nevertheless, to make sure home care is provided and to avoid rehospitalization, discharge has to be planned and include the involvement and understanding of both patient and his family. The discharge plan demands dedication from a multidisciplinary team, with interaction happening between all the professionals engaged in the health-disease process and aimed at minimizing fragmented care. Thus, solutions can

RESULTS The review’s final sample was comprised of ten articles, selected according to previously established inclusion criteria, available in the LILACS, SCIELO, and MEDLINE databases. Nine (90%) out of the ten (100%) articles selected were from nursing journals and one (10%) from the Brazilian Journal of Cardiovascular Surgery. Based on the stratification of the Personnel Development Coordination for Higher Education (CAPES) for journals, five (50%) of the articles were published in Qualis A1 and A2 journals, four (40%) in Qualis B1 and B2, and only one (10%) in Qualis B3. Regarding the time period of publication, from 2001 to 2011, five articles (50%) were published in 2006 and five (50%) between 2007 and 2011. In 2006, more professionals were willing to publish articles on this issue. In terms of the authors’ institutions, seven authors (70%) were from public federal universities and three (30%) were from hospitals, which is positive since it highlights the production of knowledge in educational institutions. However, it is important that this new knowledge gets transmitted to the nursing professionals and put into practice in hospitals. Regarding authors’ occupations, eight (80%) articles were written by female nurses; one (10%), by a male nurse and a doctor; and one (10%), by two male nurses and a biologist. This partnership between nurses and other professionals is valid as a multi-professional outlook allows for different experiences in the healthcare area and improves the quality of the assistance offered. DISCUSSION The studies revealed that nurses are concerned with the guidelines provided to patients and their families in the hospital discharge [25-31]. However, guidelines should be developed with the participation of patients and their families in a way that is easy to understand. Accordingly, nursing care should be guided by a scientific methodology that fully meets the patient’s needs. Still, studies claim that the nursing staff must develop new approaches to care with the application of nursing diagnoses and teamwork in order to have continuous care [32-34]. Among the new approaches in nursing care, a trusting relationship between nurse and patient must be readily established as it is necessary to prepare patients and their families with information about the need to undergo cardiac

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be provided based on the patient’s reality as the moment of discharge is the most expected by patients and their families. This moment is also marked by fear, insecurity, doubt, stress, and dependence upon the care of health professionals. However, the problems mentioned should be solved during the hospitalization period by the nursing staff through continuous care and with planned, implemented, and evaluated actions. Since the discharge causes a feeling of incompleteness regarding the care, it is the responsibility of the nurse to reassure the patient during this recovery process [28]. It is imperative that this professional show the patient how to take care of themselves, valuing their beliefs, feelings, actions, behaviors, and motivating them to feel able to safely develop self-care [29,31]. To this end, the nursing staff has a crucial role in providing educational activities for patients and their families by promoting knowledge and wellness, and enabling them to care for themselves. Self-care awareness is needed by the patient because it improves the practice of activities for their own benefit and quality of life. Self-care should be effectively performed and nurses should encourage it through scientific knowledge based on the General Theory of Orem Self Care. This theory emphasizes the value of engaging patients in self-care, encouraging them to participate actively in their recovery [36]. Based on this theory, educational activities that promote self-care in the postoperative period of cardiac surgery are conducted. These activities should contemplate aspects such as weight control, restriction of salt and fluids, medications, exercise, nutrition, and symptoms of worsening of the disease [27,29,31]. Besides, advice on the special care demanded by the disease and needed to handle the surgical incision and the specific conditions of each patient should be given [25]. This can make them meet and/or greatly exceed any difficulties resulting from their physical limitations as well as reduce health risks [29]. In this regard, it is understood that nursing staff must consider how the patient undergoing cardiac surgery and his family prepare for the procedure, that is, the following must be taken into account: the causes of anxiety; the perception of what is more important to advise the patient on; and how much to advise when the patient is returning home. For that purpose, nursing guidance must be well-established in the patient’s discharge plan, in a way that is clear and easy to understand. In every discharge, it can be noticed that the fragile “thank you” pronounced by the patient comes along with expressions of doubt about the care he must follow after leaving the hospital. Consequently, we highlight the importance of the nursing staff in terms of care and advising patients about actions that will contribute to a better adaptation to daily life and that will minimize their doubts and expectations [28]. However, the lack of knowledge of patients about the disease and treatment will only be solved through the guidance and educational activities provided by nurses and the

evaluation of the surgical patient in understanding the process of recovery from the time of the surgery and the implementation of post-discharge self-care. To do so, the time available and the expertise needed for the nurses to plan an individualized discharge, the availability of educational materials, and the monitoring needed to ensure the effectiveness of hospital discharge must be emphasized [30]. CONCLUSION After the results discussed, researches must be done about nursing assistance at the hospital discharge of patients in the postoperative of cardiac surgery, with the objective of drawing them to patients’ problem analysis which demand nursing specific actions, once scientific research is scarce in this field. These studies may contribute for the scientific development of the profession as well as its practical applicability in the health institutions. However, nursing care actions towards patients of cardiac surgery must be planned and involve patients and family, and discharge has to be considered from admission so that care will not be fragmented. Although we are referring to a nursing discharge planning, it is necessary to involve a multidisciplinary team and its records to set a discharge planning. So, the team must advise and develop education activities for patients and family. Moreover, the team is expected to hear and consider what participants say in order to reach their expectations and make their adaptation to a new lifestyle easier. Authors’ roles & responsibilities DFJ PFM

Study design, literature review, data collection, analysis of results and final considerations Study design with literature review, data collection, literature review, analysis and discussion of results, and final considerations

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5. Pivoto FL, Lunardi Filho WD, Santos SSC, Almeida MA, Silveira RS. Diagnósticos de enfermagem em pacientes no período pós-operatório de cirurgias cardíacas. Acta Paul Enferm. 2010;23(5):665-70.

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8. Costa VASF, Silva SCF, Lima VCP. O pré-operatório e a ansiedade do paciente: a aliança entre o enfermeiro e o psicólogo. Rev SBPH. 2010;13(2):282-98.

22. Souza MT, Silva MD, Carvalho R. Revisão integrativa: o que é e como fazer. Einstein. 2010;8(1 Pt 1):102-6.

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10. Ferreira FG, Silva RCG, Gonçalves CHB, Palomo JSH. Pósoperatório imediato de cirurgia cardíaca pediátrica: rotina de enfermagem para admissão do paciente na Unidade de Terapia Intensiva. Rev Bras Cir Cardiovasc. 2011;26(2):301-2.

24. Mendes KDS, Silveira RCCP, Galvão CM. Revisão integrativa: método de pesquisa para a incorporação de evidências na saúde e na enfermagem. Texto Contexto Enferm. 2008;17(4):758-64.

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31. Paul S. Hospital discharge education for patients with heart failure: what really works and what is the evidence? Crit Care Nurse. 2008;28(2):66-82.

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Valente AS, et al. - COMUNNICATION Supravalvular aortic stenosis in adult with anomalies of SHORT aortic arch vessels and aortic regurgitation

Supravalvular aortic stenosis in adult with anomalies of aortic arch vessels and aortic regurgitation Estenose aórtica supravalvar em adulto com anomalia de vasos da base e insuficiência aórtica

Acrisio Sales Valente1, MD, PhD; Polyanna Alencar2; Alana Neiva Santos2; Roberto Augusto de Mesquita Lobo1, MD; Fernando Antônio de Mesquita1, MD; Aloyra Guedis Guimarães1, MD DOI: 10.5935/1678-9741.20130088

RBCCV 44205-1510

Abstract The supravalvular aortic stenosis is a rare congenital heart defect being very uncommon in adults. We present a case of supravalvular aortic stenosis in adult associated with anomalies of the aortic arch vessels and aortic regurgitation, which was submitted to aortic valve replacement and arterioplasty of the ascending aorta with a good postoperative course.

Resumo A estenose aórtica supravalvar é uma rara cardiopatia congênita, bastante incomum em adultos. Apresentamos um caso de estenose aórtica supravalvar em adulto com anomalia de vasos do arco aórtico, já com presença de insuficiência aórtica importante, tratado com êxito por meio de plastia da aorta ascendente e troca valvar aórtica.

Descriptors: Aortic stenosis, supravalvular. Aortic valve insufficiency. Adult. Subclavian artery. Carotid artery, internal.

Descritores: Estenose aórtica supravalvular. Insuficiência da valva aórtica. Adulto. Artéria subclávia. Artéria carótida interna.

INTRODUCTION

The main clinical characteristics of the SAS are syncope, dyspnea and palpitations and the incidence of these symptoms is the earliest the progression of the disease. In general, the disease is most commonly diagnosed in children, due to the presence of blow associated to the obstruction [5]. The presence of adults with untreated SAS is even more unusual. This is due to failure to detect the disease or diagnostic inaccuracy. We believe that some associated diseases, such as aortic coarctation and malformations of the great vessels may contribute to diagnostic errors or questions that often postpone the appropriate definitive treatment. Late diagnosis of SAS may result in progressive symptoms, damage to the aortic and mitral valve, and ventricular dysfunction, which draws attention to the need for knowledge of the forms of the disease and its variations.

The supravalvular aortic stenosis (SAS) is the least common form of obstruction of the left ventricular outflow tract, representing 0.05% of all congenital heart disease [1-3]. It is characterized as a congenital obstruction of the ascending aorta, most commonly involving the sinotubular junction and may occur as a dysmorphia like an “hourglass” or as a diffuse hyperplasia. This malformation can occur as an aspect of Williams syndrome, being the most common cardiac defect of this syndrome [4] an autosomal dominant inherited familial form not associated with Williams syndrome and may also occur in patients with no family history and patients with homozygous familial hypercholesterolemia, occurring in up to 44% of cases in this presentation [5].

1 2

Correspondence address: Acrisio Sales Valente Rua Alberto Feitosa Lima 180 – apt. 602 – Guararapes – Fortaleza, CE, Brazil – Zip code 60810-018 E-mail: acrisiovalente@yahoo.com

. São Raimundo Hospital, Fortaleza, CE, Brazil. . Christus Medical School, Fortaleza, CE, Brazil.

This study was carried out at at the São Raimundo Hospital, Fortaleza, CE, Brazil.

Article received on May 12th, 2012 Article accepted on July 13th, 2013

Financial support: São Raimundo Hospital.

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CASE REPORT

Abbreviations, acronyms & abbreviations CPB ACo SAS LVM BCT LV

AST, male patient, 28 years old, with a history of heart murmur since birth, with no symptoms. In 2006, performed an echocardiogram which showed mild left ventricular hypertrophy with left ventricular mass (LVM) of 277g, reference value 94-276g, and mild mitral and aortic regurgitation. In 2008, performed another echocardiography, which showed mild dilation of the left ventricle (LV) with preserved function, mild mitral and moderate aortic regurgitation. Aortic coarctation (ACo) with peak systolic gradient of 49 mmHg was suggested. Although asymptomatic, the patient did not seek medical treatment assistance, performing new echocardiogram the following year, being evidenced increased LVM of 293g, normal ventricular function, mild mitral regurgitation and moderate aortic coarctation and suggestive sign of the left subclavian artery, with gradient 49 mmHg.

Cardiopulmonary bypass Aortic Coarctation Supravalvar aortic stenosis Left ventricle mass Brachiocephalic trunk Left ventricle

We present a rare case of SAS in adults, not related to Williams syndrome, already with aortic valve dysfunction and anomalous origin of the great vessels, which may have favored the diagnostic difficulties. This study was submitted to the Research Ethics Committee of the Hospital S達o Raimundo and approved under registration 04/2012.

Fig 1 - CT angiography. Preoperative angiography. A: severe supravalvular aortic stenosis. B: anomalies of the great vessels with left common carotid artery originating from the BCT and hypoplastic left subclavian artery. C: Severe supravalvular aortic stenosis in another incidence. Post-operative images. D and E: good opening towards systemic output. F: external aspect of the aorta.

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In 2010, the patient came to our Service. A new echocardiogram was performed which showed: mild aortic regurgitation, aortic coarctation with a peak systolic gradient of 45 mmHg, located below the left subclavian artery, and LV concentric hypertrophy of mild degree. The patient was asymtomatic, referring fatigue on exertion and occasional syncope. On physical examination, the patient was in good general condition, cardiac auscultation with regular cardiac rhythm with two clicks, normal heart sounds, presence of more audible systolic murmur in the aortic area, radiating to the neck. The presence of pulses in the lower and upper differential pressure between upper limbs called our attention, with higher right pressure. Then, we questioned the diagnosis of aortic coarctation. Then, we performed angiography, which showed supravalvular aortic stenosis, severe aortic valve insufficiency and hypoplasia of the left subclavian artery with origin of the left carotid artery from the brachiocephalic trunk (BCT). For greater morphological detail, was also performed chest angiography, which showed patent ascending aorta, and showed significant supravalvular stenosis, 2.2 cm long, lying 2 cm from the emergence of the BCT (Figure 1). Surgical treatment was indicated and performed in 2011.

We opted for the aortic valve replacement with a mechanical double-leaflet prosthesis type number 23 and enlargement of the ascending aorta with single bifurcated patch of bovine pericardium, extending from the ascending aorta to the right coronary and non-coronary sinus. It is important that the right coronary ostium is carefully viewed. The pericardial patch should be large enough to allow certain bulging in the region of the open sinuses of Valsalva, simulating the natural anatomical aspect. In our experience, the cropped patch seems to always be a little bigger than necessary. After suturing, the final appearance is quite anatomical (Figure 2). Biological glue was used to enhance hemostasis. After rewarming, the patient was removed from CPB without difficulty and surgery was fully performed traditionally. The surgery was uneventful in 3 hours and 30 minutes, with 80 minutes of CPB and 40 minutes of aortic clamping. Evolution The patient was extubated in the immediate postoperative period and remained three days in the intensive care unit and total hospital stay of seven days. In return fifteen days after the surgery, the patient was asymptomatic, in good recovery. With two months of surgery, control echocardiogram was performed, which showed: LVM 260g, cardiac chambers of normal dimensions, metallic prosthesis in the aortic position with good handling of its leaflets, the Doppler peak systolic gradient of 37 mmHg and mean of 21 mmHg with minimal central regurgitation. Angiography showed patent ascending aorta, preserved gauge, showing mild irregularity of the contours in the cranial aspect of the distal segment, before the emergence of BCT (Figure 1). With six months after surgery, the patient remained asymptomatic and the echocardiogram showed LVM of 230g, normal cardiac cavities, prosthesis with peak systolic gradient of 25 mmHg and a minimum central “escape”.

Surgical technique The patient underwent surgery for expansion of the ascending aorta and aortic valve treatment. Surgery was performed with cardiopulmonary bypass (CPB), bicaval cannulation and ascending aorta, systemic and topical moderate hypothermia, aortic cross-clamping and administration of intermittent hypothermic blood cardioplegic solution every 30 minutes. The aortotomy was performed in inverted “Y”, extending to the non-coronary sinus and the right coronary. The great thickening of the aortic wall drew attention. The valve had become thickened and deformed, with the presence of deposits of fat and calcium plaques.

Fig. 2 - Images from the surgery. Aortotomy in inverted “Y”, thickened aorta. Mechanical aortic prosthesis positioned. Final external appearance, with a pericardial patch extending to the right coronary and non-coronary sinus.

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DISCUSSION

techniques without the use of prosthetic material are attractive, especially in children, as suggested by Souza et al. [9]. In adult patients, the reduced elasticity of the aorta and stenotic segments sometimes more extensive has made us opt for enlargements using patches, which, in our experience, are more simple and fast techniques, and effective, especially considering that there are no adults in the concern with growth. In this particular case, after aortotomy, the valve seemed inadequate to the plastic, making us choose to replacement using a mechanical prosthesis, which was previously discussed with the patient. In continuation, the anatomical aspect of the aorta, with apparently normal left coronary sinus, made ​​us conclude that the expansion in inverted “Y” would be an excellent option in this case. This technique was originally described by Doty et al. [10] for moderate or severe supravalvular aortic stenosis not involving significant narrowing of the left coronary sinus of Valsalva, as in the reported case. In this case, we use large bovine pericardium patch. It could also be used a polytetrafluoroethylene patch, with the advantage of not presenting calcification, but have no such material available. We believe that one should not dry the curvature of the left coronary sinus in order to leave the suture line straight at that point. Maintaining the natural design, or that is, the vertices of the inverted “Y”, while leaving a little longer suture line, helps shape the enlargement patch after release of aortic clamping. The final touch with biological glue has been a good additional factor in the hemostatic arsenal and we have used regularly. The patient developed well after surgery. The earlier surgery might spare him the replacement of the native valve, but fortunately he had no ventricular dysfunction. The echocardiographic assessment also showed the satisfactory outcome of the surgery.

The SAS is an uncommon congenital heart disease and should be diagnosed early for surgical indication before its effects compromise other structures and, importantly, aortic valve and LV. When more commonly diagnosed in childhood, it allows early treatment planning and thus avoids major structural impairment of the heart. The coronary arteries, due to high pulse pressure which they are subjected under this condition can also undergo structural changes as described by Peterson et al. [6]. Thus, for all these peculiarities, invasive therapy in the SAS should be earlier than in aortic stenosis [5]. Since the initial reports of Usher et al. [7] and Weyman et al. [8], echocardiography has been the initial diagnostic examination in most cases . Some aspects related to abnormalities of the great vessels, poorly assessed by examination, may impair the diagnosis and make other complementary image tests necessary. The insidious symptoms, associated with diagnostic doubts along the clinical investigation transmitted to the patient, favors his more relaxed behavior, insecure and rejection of closer monitoring, delaying diagnosis, as reported to us in an interview later. We believe that the hypoplastic subclavian artery caused false impression of aortic coarctation, described in various examinations performed by different operators. The same finest subclavian artery was also responsible for the differentiation of pulse and pressure between the upper limbs (high blood pressure in right arm in relation to the left), confusing the examiners. The diagnostic uncertainty should always raise the employment of more complex tests. The idea of coarctation raised such questioning, considering that the patient had lower limb pulses. Thus, we chose to perform angiography also to assess coronary arteries and CT. We believed that progressive aortic insufficiency was related to obstruction immediately after the valve, causing its abnormal turbulence. Echocardiography suggested thickened valve with poor coaptation. The same impression we did not had of the mitral valve, which appeared thin at echocardiography with mild prolapse of its brochure. The patient also had begun to show symptoms, which led us to decide the immediate surgical treatment. Surgical planning, considering that both carotid arteries leaves emerge from common trunk, we concerned about the possible need to cannulate the BCT through a tubular graft, what we have done regularly when we need to work freely in the ascending aorta and aortic arch. We feared that some ostium was not well perfused. However, if necessary, we may cannulate the femoral artery. During surgery, angiography confirmed the impression that there was space for safe cannulation of the ascending aorta before BCT, which was performed. For the correction of the stenotic aortic segment,

Authors' roles & responsibilities ASV PA ANS RAML FAM AGG

Study design, surgeon of the case supervisor Survey records, literature review, references research Survey records, literature review, references research Surgeon of the case, co-advisor Surgeon of the case, co-advisor Echocardiographist and cardiologist of the case, material collection

REFERENCES 1. Heper G, Kose S, Kilic A, Amasyali B, Isik E. Left ventricular apical aneurysm as a consequence of diffuse type congenital nonfamilial supravalvular aortic stenosis in a 30-year-old female. Int Heart J. 2005;46(1):153-9.

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2. Micale L, Turturo MG, Fusco C, Augello B, Jurado LA, Izzi C, et al. Identification and characterization of seven novel mutations of elastin gene in a cohort of patients affected by supravalvular aortic stenosis. Eur J Hum Genet. 2010;18(3):317-23.

6. Peterson TA, Todd DB, Edwards JE. Supravalvular aortic stenosis. J Thorac Cardiovasc Surg. 1965;50(5):734-41. 7. Usher BW, Goulden D, Murgo JP. Echocardiographic detection of supravalvular aortic stenosis. Circulation. 1974;49(6):1257-9.

3. B o n i n i R C A , P a l a z z i E M , C h a c c u r P, S o u s a L C B . Correção cirúrgica da estenose aórtica supravalvar com modificação da técnica de Sousa. Rev Bras Cir Cardiovasc. 2010;25(2):253-6.

8. Weyman AE, Caldwell RL, Hurwitz RA, Girod DA, Dillon JC, Feigenbaum H, et al. Cross-sectional echocardiographic detection of aortic obstruction. 2. Coarctation of the aorta. Circulation. 1978;57(3):498-502.

4. Sugayama SMM, Moisés RL, Wagenfur J, Ikari MN, Abe KT, Leone C et al. Síndrome de Williams-Beuren. Anomalias cardiovasculares em 20 pacientes diagnosticados pela hibridização in situ por fluorescência. Arq Bras Cardiol. 2003;81(5):462-7.

9. Souza LCB, Chaccur P, Dinkhuysen JJ, Fontes MA, Fontes VF, Abdulmassih Neto C, et al. Modificação técnica na cirurgia da estenose aórtica supravalvar. Rev Bras Cir Cardiovasc 1992;7(2):121-6.

5. Valente AS, Cirino CMF. Cardiopatia congênita no adulto. In: Croti UA, Mattos SS, Pinto Jr. VC, Aiello VD, eds. Cardiologia e cirurgia cardiovascular pediátrica. São Paulo: Roca; 2008.

10. Doty DB, Polansky DB, Jenson CB. Supravalvular aortic stenosis. Repair by extended aortoplasty. J Thorac Cardiovasc Surg. 1977;74(3):362-71.

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Shi H, et al. - UseHOW of a stent-graft and vascular occlude to treat primary and TO DO IT re-entry tears in a patient with a Stanford type B aortic dissection

Use of a stent-graft and vascular occlude to treat primary and re-entry tears in a patient with a Stanford type B aortic dissection O uso de endoprótese e oclusor vascular para tratar ruptura primária e de re-entrada em paciente com dissecção aórtica tipo B de Stanford

Huihua Shi1, Min Lu1, Mier Jiang1

DOI: 10.5935/1678-9741.20130089

RBCCV 44205-1511

Abstract Thoracic endovascular aortic repair for aortic dissections is recognized as an effective treatment. We herein report the case of a 72-year-old male with a Stanford type B aortic dissection. A stent-graft and double-disk vascular occluder was used to repair the primary and re-entry tears, respectively. At 3 month postoperatively, computed tomographic angiography revealed no endoleaks, the stent-graft and vascular occluder to be in optimal positions, the false lumen was almost completely thrombosed, and the visceral arteries were patent. This case illustrates that it is feasible to treat re-entry tears with a vascular occluder after primary proximal stent-graft repairs.

Resumo Reparação endovascular de aorta torácica para dissecção aórtica é reconhecida como um tratamento eficaz. Relatamos o caso de um homem de 72 anos de idade, com dissecção aórtica tipo B de Stanford. A endoprótese e oclusor duplo disco vascular foi usado para reparar as rupturas primária e de re-entrada, respectivamente. Aos três meses de pós-operatório, angiotomografia computadorizada não revelou vazamentos, o oclusor e a endoprótese vascular estavam em posições melhores, a falsa luz foi quase completamente trombosada, e as artérias viscerais estavam patentes. Esse caso demonstra que o tratamento de rupturas na re-entrada com endoprótese vascular após reparos proximais primários é viável. Descritores: Doenças vasculares. Procedimentos cirúrgicos vasculares. Doenças da aorta.

Descriptors: Vascular diseases. Vascular surgical procedures. Aortic diseases.

Correspondence address: Min Lu Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of Medicine Zhizaoju road, 639, Shanghai, the People’s Republic of China - Zip code: 200011 E-mail: lmminlu@yeah.net Article received on December 6th, 2012 Article accepted on September 2nd, 2013

Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai, China. 1

No financial support. Work carried out at Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai, China.

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clavian artery, and a re-entry tear below the superior mesenteric artery orifice (Figure 2A). The right renal artery was not visualized, the kidney was atrophic and flow was from the false lumen. The patient was taken to the operating room within 48 hours of the computed tomography angiography. After induction of general anesthesia a 5F sheath was inserted into the left axillary artery, and a centimeter sizing 5F pigtail catheter (Cook, USA) was introduced into the ascending aorta through the left subclavian artery. A 5F pigtail catheter was introduced into the ascending aorta through the femoral artery. Angiography was performed in two projections, left anterior oblique and anteroposterior. First, the 5F pigtail catheter was confirmed to be in the true lumen, and then the precise location of the primary tear was identified to be 2 cm distal to the left subclavian artery. By using the centimeter sizing pigtail catheter, the diameter of the landing zone was measured and compared to that determined by computed tomography angiography. Before the deployment of the stentgraft, heparin (1 mg/kg) was given intravenously. An extra-stiff guidewire (Lunderquist, Cook, USA) was threaded into the ascending aorta through the pigtail catheter, and the delivery system was introduced to the appropriate position over the guidewire. A tube-shaped stent-graft (Zenith TX2 32Ă—160 mm, Cook, USA) was deployed under fluoroscopy. Angiography was performed to confirm the correct position and that there were no endoleaks. A 10 mm wide re-entry tear was found below the superior mesenteric artery orifice and opposite to left renal artery. Because the re-entry tear and false lumen were so large, and right renal artery was atrophic, we decided to use an occluder to seal the re-entry tear.

Abbreviations, acronyms & symbols TEVAR

Thoracic endovascular aortic repair

INTRODUCTION Aortic dissection is the most common acute emergency involving the aorta, and often results in death. The incidence of aortic dissection has been reported to be 2,000 new cases per year in the United States and 3,000 in Europe [1-4]. The efficacy and safety of thoracic endovascular aortic repair (TEVAR) for acute [5-7] and chronic [8-10] aortic dissections has been shown in a many studies. As our experience with TEVAR has increased, the importance of re-entry sites (secondary tears) has drawn attention [11,12]. Herein we report a case in which we applied a stent-graft and double-disk vascular occluder to repair the primary and re-entry tears, respectively, in a patient with Stanford type B aortic dissection. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. This study was approved by the Institutional Review Board of Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of Medicine (number is 201293). CASE REPORT A 72-year-old male was admitted with a complaint of chest discomfort for 1 month. Computed tomography revealed an aortic dissection with entry and re-entry tears (Figure 1). Angiography then demonstrated a Stanford type B aortic dissection with the primary tear distal to the left sub-

Fig. 1 - Computed tomography revealed an aortic dissection with entry and re-entry tears.

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Fig. 2 - A) Angiography demonstrated a Stanford type B aortic dissection with the primary tear distal to the left subclavian artery, and a re-entry tear below the superior mesenteric artery orifice. B) After occluder placement

Fig. 3 - Computed tomography (CT) images of the false lumen. A) A large false lumen was identified in the abdominal aorta before surgery. B) At 3 month postoperatively CT revealed thrombosis in the descending false lumen and (C) thrombosis in the abdominal false lumen

A 9F long sheath with a Cobra-shaped tip (SFA9F Occluder Transmission System; Lifetech Scientific Co. Ltd, Shenzhen, China) was advanced over the guidewire to the false lumen through the re-entry tear. Sized to exceed the 10 mm diameter re-entry tear by 2 mm, the waist of the 12-mm double-disk symmetrical occluder (SearCare; Lifetech Scientific Co. Ltd) was connected to the tip of the delivery cable by a microscrew fixed to the posterior disk, and collapsed into a loader. The collapsed device was then advanced into the sheath by pushing the delivery cable. Under fluoroscopic guidance, the anterior disk (26 mm) was deployed in the false lumen against the dissection flap after passing through the rupture, and the waist of the occluder was placed in the re-entry tear, which was both felt and observed by fluoroscopy. Then, the posterior disk (22 mm) was deployed by further withdrawal of the sheath. The position of the occluder within the re-entry tear was determined to be in a secure and stable position by

gentle pushing and pulling of the delivery cable. The occluder was released by unscrewing; the conveyor was rotated counterclockwise to separate after angiography had verified its position and ruled out interference with aortic branch vessels. On completion angiography, the device was in an optimal position and the re-entry tear was covered. There was no leakage into the false lumen and the superior mesenteric artery and left renal artery were patent (Figure 2B). The patient recovered uneventfully and no complications occurred being discharged 2 weeks later in good condition (in China, hospital stays are routinely much longer than in other countries). At 3 month postoperatively, computed tomography revealed thrombosis in the descending false lumen and thrombosis in the abdominal false lumen (Figure 3). No endoleaks were noted, the stent-graft and vascular occluder were in optimal positions, and the visceral arteries (except the right renal artery) were patent.

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DISCUSSION

common carotid artery - left subclavian artery bypass was performed to treat the dissection. Then, the proximal entry tear was obliterated with a ventricular septal defect occluder. Tang et al. [11] reported the case of a 34-year-old female in which a type I endoleaks and a patent reentry tear above the celiac artery orifice was noted 6 months after stent-graft repair of a type B aortic dissection. The reentry tear was successfully treated with a double-disk vascular occluder. Compared with other occluders, the SearCare self-expanding nitinol double-disk device uses its short connecting waist to dock at the re-entry tear, forcing blood to flow through the access filled with thrombogenic polytetrafluoroethylene material. The device is symmetrical in design, the centers of the anterior and posterior disks are on the same axis, and the anterior disk is larger than the posterior disk, which can be customized to seal the re-entry tear and avoid covering the adjacent branch vessels. We chose a device size 2 to 3 mm larger than the size of the re-entry tear. Sheath size depends on the size of the occluder chosen for closure. In this patient, the re-entry (10 mm) was below the superior mesenteric artery orifice, so a 12 mm symmetrical device and a 9F long sheath were used. Selecting the type and size (waist diameter) of the occluder should be planned based on the computed tomography angiography prior to the procedure, and then confirmed by intraoperative angiography. An excessively large waist may tear the intima, influence the final configuration of the occluder, and even interfere with the hemodynamics of adjacent visceral arteries. The re-entry may take an acute angle off the longitudinal aortic axis, causing some difficulties in guidewire engagement during the procedure. One solution, which we adopted in this case, is to pre-shape the guidewire and sheath with a long preshaped Cobra sheath to successfully engage the re-entry tear. Occluders generally yield good results with few procedural difficulties; however, complications that have been reported include device migration [16,17] and inaccurated placement [18]. The primary limitation of this report is that long-term follow-up is lacking.

The ideal results after TEVAR include aortic reconstruction and false lumen thrombosis or resolution. Adequate sealing of primary entry tears in the descending thoracic aorta after stent-graft placement can reduce pressure in the false lumen to avoid further dilatation or rupture. In acute onset aortic dissections, if there are no endoleaks or re-entry tears the false lumen will be completely obliterated within 6 months after stent-graft placement [13]. Compared with acute aortic dissections, chronic dissections may have one or more re-entry tears in the abdominal aorta and a un-thrombosis abdominal false lumen originating from persistent flow or pressure through the re-entry tear [810]. In our case of subacute dissection, because the re-entry site diameter was large it was unlikely to seal spontaneously. The false lumen would progressively dilate as a result of a patent re-entry site in the abdominal aorta, and the risk of rupture would persist. A study by Dias et al. [14] in which endovascular treatment was used to treat 11 patients with chronic type B aortic dissections found that although stentgraft deployment was technically successful in all patients false lumen flows persisted in the thorax in 27% of the patients and in the abdomen in 82%, and that aortic diameter was not decreased postoperatively. The authors concluded that endovascular treatment of chronic type B dissections is not effective as it does not decrease aortic diameter. Other studies, however, have indicated that endovascular treatment is effective for chronic aortic dissections [8-10]. Jia et al. [8] reported lower aorta-related mortality in patients with chronic type B dissections treated with stent-grafting as compared to those treated with medical management and a decrease of thoracic aorta diameter from a mean of 42.4 mm to 37.3 mm in the TEVAR group. Andacheh et al. [9] reported expansion of the thoracic true lumen and regression of the false lumen in patients following TEVAR, and similarly Parsa et al. [10] found depressurization of the false lumen after TEVAR. As re-entry tears in the abdominal aorta tend to be located near the branch vessels, they are generally unfavorable for exclusion with a stent-graft because the branch ostia may be partially covered, which may lead to ischemia of the spinal cord, liver, intestine, gallbladder, or kidney. In our case, we believe that the atrophy of the right kidney was a result of the dissection. Though hybrid techniques that combine traditional surgery to place bypass grafts between the visceral arteries and abdominal aorta before endovascular intervention to expand the applicability of TEVAR are used, we have found this strategy significantly increases surgical trauma and difficulty. Few studies have reported the combined use of stent-grafts and occluders for the treatment of chronic type B dissections. Chang et al. [15] reported the endovascular repair of a type B aortic dissection in which the proximal entry tear was 5 mm distal to the orifice of the left subclavian artery. Ascending aorta-left

CONCLUSION The double-disk vascular occluder is a minimally invasive option compared with hybrid surgery. Our experience suggests that the use of this occluder is feasible, efficacious, and safe. Authors’ roles & responsibilities HS ML MJ

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Performed research/study, managed the literature searches and analyses, wrote the first draft of the manuscript Designed the study and wrote the protocol, performed research/ study, critically reviewed the manuscript Designed the study and wrote the protocol

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10. Parsa CJ, Williams JB, Bhattacharya SD, Wolfe WG, Daneshmand MA, McCann RL, et al. Midterm results with thoracic endovascular aortic repair for chronic type B aortic dissection with associated aneurysm. J Thorac Cardiovasc Surg. 2011;141(2):322-7.

REFERENCES

1. Mehta RH, Suzuki T, Hagan PG, Bossone E, Gilon D, Llovet A, et al; International Registry of Acute Aortic Dissection (IRAD) Investigators. Predicting death in patients with acute type a aortic dissection. Circulation. 2002;105(2):200-6.

11. Tang X, Fu W, Xu X, Yang J, Shi Y, Yan Z, et al. Use of a vascular occluder to treat a re-entry tear in a patient with Stanford type B aortic dissection: acute and 1-year results. J Endovasc Ther. 2008;15(5):566-9.

2. Hagan PG, Nienaber CA, Isselbacher EM, Bruckman D, Karavite DJ, Russman PL, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease. JAMA. 2000;283(7):897-903. 3. Wheat MW Jr. Acute dissecting aneurysms of the aorta: diagnosis and treatment:1979. Am Heart J. 1980;99(3):373-87.

12. Hausegger KA, Tiesenhausen K, Schedlbauer P, Oberwalder P, Tauss J, Rigler B. Treatment of acute aortic type B dissection with stent-grafts. Cardiovasc Intervent Radiol. 2001;24(5):306-12.

4. Nienaber CA, Fattori R, Mehta RH, Richartz BM, Evangelista A, Petzsch M, et al; International Registry of Acute Aortic Dissection. Gender-related differences in acute aortic dissection. Circulation. 2004;109(24):3014-21.

13. Qin YL, Deng G, Li TX, Jing RW, Teng GJ. Risk factors of incomplete thrombosis in the false lumen after endovascular treatment of extensive acute type B aortic dissection. J Vasc Surg. 2012;56(5):1232-8.

5. Nienaber CA, Rousseau H, Eggebrecht H, Kische S, Fattori R, Rehders TC, et al; INSTEAD Trial. Randomized comparison of strategies for type B aortic dissection: the INvestigation of STEnt Grafts in Aortic Dissection (INSTEAD) trial. Circulation. 2009;120(25):2519-28.

14. Dias RR, Judas G, Oliveira MA, Malbouisson LM, Fiorelli AI, Stolf NA. Is the endovascular procedure an option for treatment of chronic type B aortic dissections? Rev Bras Cir Cardiovasc. 2007;22(4):441-7. 15. Chang G, Wang H, Chen W, Yao C, Li Z, Wang S. Endovascular repair of a type B aortic dissection with a ventricular septal defect occluder. J Vasc Surg. 2010;51(6):1507-9.

6. Fioranelli A, Razuk Filho A, Castelli JĂşnior V, Karakhanian W, Godoy JM, Caffaro RA. Mortality within the endovascular treatment in Stanford type B aortic dissections. Rev Bras Cir Cardiovasc. 2011;26(2):250-7.

16. Goel PK, Kapoor A, Batra A, Khanna R. Transcatheter retrieval of embolized AMPLATZER Septal Occluder. Tex Heart Inst J. 2012;39(5):653-6.

7. Hughes GC, Andersen ND, McCann RL. Management of acute type B aortic dissection. J Thorac Cardiovasc Surg. 2013;145(3 Suppl):S202-7. 8. Jia X, Guo W, Li TX, Guan S, Yang RM, Liu XP, et al. The results of stent graft versus medication therapy for chronic type B dissection. J Vasc Surg. 2013;57(2):406-14.

17. Vottero GV, Niclauss L, Marcucci C, Hurni M, von Segesser LK. Late migration of percutaneous bioabsorbable devices--a word of caution. J Card Surg. 2012;27(2):183-5.

9. Andacheh ID, Donayre C, Othman F, Walot I, Kopchok G, White R. Patient outcomes and thoracic aortic volume and morphologic changes following thoracic endovascular aortic repair in patients with complicated chronic type B aortic dissection. J Vasc Surg. 2012;56(3):644-50.

18. Gomez-Rubin MC, Ruiz-Cantador J, Polo L, LopezFernandez T, Gonzalez A, Oliver JM, et al. Platypneaorthodeoxia syndrome after failed percutaneous closure of secundum atrial septal defect. Congenit Heart Dis. 2012;7(5):E70-2.

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Evora PRB, et IN al. -CARDIOVASCULAR Terminal right coronary artery fistula to right ventricle IMAGES SURGERY

Terminal right coronary artery fistula to right ventricle Fístula terminal da artéria coronária direita para o ventrículo direito

Paulo Roberto B. Evora, MD PhD, Solange Bassetto, MD, Alfredo J. Rodrigues, MD PhD DOI: 10.5935/1678-9741.20130090

RBCCV 44205-1512

A 57 year-old man, obese, with history of hypertension, dyslipidemia, smoking and two previous ischemic strokes, was admitted with a six month history of chest pain associated with dyspnea on moderate and large efforts. He was hemodynamically stable and making use of captopril, aspirin, hydrochlorothiazide and metroprolol. There was no mention of chest murmur in the hospital admission record. A routine Doppler echocardiogram showed normal results and no mention of coronary fistula. Coronary angiography revealed lesions in the left main coronary artery (60-70%); left anterior descendent artery (LAD) (80%), and proximal lesions in the right coronary artery (RCA) (50%). In addition it casually revealed the presence of a terminal coronary-cavitary fistula arising from the RCA and shunting blood to the right ventricle. The surgical findings revealed diffuse calcifications of proximal coronary arteries. Interestingly, the RCA had normal appearance near the fistula. Surgery consisted of dissection and exposure of the fistula before cardiopulmonary bypass (CPB) (Figure B), followed by ligation on CPB (Figures C and D), and CABG (LITA anastomosis in situ for LAD and left coronary circumflex artery radial artery graft). It is difficult to discuss coronary fistula hemodynamic and clinical repercussions due to the patient comorbidities, particularly the severity of coronary artery disease. From the surgical findings, it is highly probable that the fistula is a congenital type B malformation in the Sakakibara classification [1].

REFERENCE

1. Sakakibara S, Yokoyama M, Takao A, Nogi M, Gomi H. Coronary arteriovenous fistula. Nine operated cases. Am Heart J. 1966;72(3):307-14. Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo Ribeirão Preto, SP, Brazil

Correspondence Address: Paulo Roberto Evora, Rua Rui Barbosa, 367, 14015-120 Ribeirão Preto, SP, Brazil E-mail: prbevora@gmail.com Article received on October 30th, 2013 Article accepted on November 10th, 2013

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Dallan LAO, etPOINT al. - Words the young cardiovascular surgeon OFtoVIEW

Words to the young cardiovascular surgeon Palavras ao jovem cirurgião cardiovascular How to conduct yourself in the initial procedures of myocardial revascularization Como se conduzir nos procedimentos iniciais de revascularização do miocárdio

Luís Alberto O. Dallan, PhD1 DOI: 10.5935/1678-9741.20130091

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Reproduction of the lesson presented at the 40th Brazilian Congress of Cardiovascular Surgery Florianópolis, SC – 2013

When surgery is very difficult, I always joke with my staff: “Imagine you, in your first event in the new service, operating the Mayor’s mother, with this coronary pattern.” Or, I say “The eight children are there waiting in the lobby of the operating room, but do not worry, they do not understand much of medicine: One of them is jailer, another is a lawyer - but very annoying, and a professional assassin, but he is on parole! They are waiting for their mummy to be discharged perfectly well! or like in the Northeast, when the Colonel says that the mother will not die alone!” Even after experienced, we have to take all precautions to avoid trouble: - perhaps the first orientation, wiser, is not to try early in the career making all revascularization without CPB. Use the CPB, except when treating only the arteries of the anterior wall. See below a quick overview of current results of surgery with and without cardiopulmonary bypass:

I see two phases of the young surgeon: 1st - Still in the rearward, receiving direct assistance, or having a teacher available. The simple fact of knowing that there is someone more experienced that can be consulted, already provides him incredible confidence. In “solo flight”, for example: starting a Service (and this is not the privilege of someone too young): Surely one chill run down his spine, especially the day before, when speaking to the patient’s family. If there is no certain fear, there is something wrong with this surgeon. Probably, he is very impetuous. When starting the surgery, I’m sure there will be some degree of hesitation. I make a parallel to a rookie playmaker on a sports team, with great care, expectations and pressure for performance.

Article received on November 14th, 2013 Article accepted on November 27th, 2013

Heart Institute of the Clinics Hospital at Faculty of Medicine of the University of São Paulo (InCor HCFMUSP), São Paulo, SP, Brazil 1

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A second orientation is to know indicate the surgery. Find the orientation of the Guidelines and of common sense. For good sense is understood: - Planning surgery with a HEART TEAM: surgeon, clinical and hemodynamicist. If possible, do not consider the latter as an enemy, but as a possible ally in complex cases, or when something goes wrong in the postoperative period. - Chatting with family, explaining the risks. Many from University Hospitals are not used to it. - Trying to integrate the anesthetist in the spirit of each surgery. Currently, I always try to show the catheterization of the patient to the anesthesiologist. - Also, with the perfusionist. Do not forget that for one or more hours, your patient will be in your hands, and poor perfusion can put everything away. - Over time, you will learn to master the entire environment during operation. It is very common for the surgeon to do a number of alert during operation, for example, the blood is dark, presence of lung atelectasis, the patient's blood is too hot. I've seen asking to stop the lungs momentarily and forgetting to reconnect it. Do not forget that if there is any problem, surely the greater responsible will be the surgeon, even if he does not have anything to do the complication. Don't push your luck: For example, foreign body. It is un-

forgivable to forget gauze, a little compress, even a bulldog inside the patient. I've seen or heard it all and believe me, it is likely to occur. You must be obsessive in such matter! Also learn to give instructions to the room. The typical example is the shock (I've learned from Dr. Bittencourt). If many ask at the same time to trigger it, it turns into a mess. A third guideline is that I've learned over time: - It takes about 10 years to learn to operate. However: - It takes about 15 years to learn how to indicate surgery. - It takes about 20 years to learn to contraindicate surgery. At the beginning, do not feel unable or ashamed to seek advice from those who have been through it all. Often a phone call solves the issue. Concluding, MRI should be at the discretion of the surgeon. That does not mean that everything has gone well! I mean that in the immediate postoperative period the surgeon has security to assume an attitude which can also be an addition to surgery in hemodynamics. The last recommendation is to see the patient in the immediate and late postoperative period. Take this as a routine, which will certainly avoid many problems and improve results. Be successful!

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Changing scientific communication ERRATUM/ERRATA

ERRATUM/ERRATA

DOI: 10.5935/1678-9741.20130092

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In the printed version of the 28.3 issue the Figure 1 of the article “Impact of aspirin use in the incidence of thromboembolic events after bioprosthesis replacement in patients with rheumatic disease” (pages 347 to 352) was not published. Below, the figure:

Fig. 1 – Stroke free survival

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th TH Abstracts of 13 Congress of SCICVESP (Society of Cardiovascular Surgery 13 CONGRESS OF SCICVESP of São Paulo)

Abstracts of 13th Congress of SCICVESP (Society of Cardiovascular Surgery of São Paulo) Resumos dos trabalhos apresentados no 13º Congresso da SCICVESP (Sociedade de Cirurgia Cardiovascular do Estado de São Paulo)

DOI: 10.5935/1678-9741.20130093

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TL - 01 TRATAMENTO MINIMAMENTE INVASIVO DA VALVA MITRAL PELO 4° ESPAÇO INTERCOSTAL DIREITO: PINÇAMENTO DIREITO DA AORTA OU USO DE CATETER DE OCLUSÃO ENDOAÓRTICO?

confirmado por Ecocardiograma pós-operatório (PO). No subgrupo de pinçamento direto da aorta (11 pacientes), uma prótese teve que ser reimplantada por motivos técnicos, levando a CEC prolongada que evoluiu para coagulopatia no PO sendo necessário reabordagem cirúrgica (9%). Um paciente, com recusa operatória há 1 ano, apresentou episódio de edema agudo pulmonar. Após compensação, foi operado mas evoluiu com falência respiratória sendo diagnosticado fibrose pulmonar vindo a falecer no 260 PO (9%). No subgrupo do dispositivo de oclusão endoaórtico (5 pacientes), ocorreu 1 episódio de AVC transoperatório com seqüela motora (20%), e um episódio de AVC no 20 PO em uma paciente de 73 anos com plastia prévia da valva Mitral. Esta paciente só poderia ser operada pelo 40 EICD neste subgrupo por ser reoperação. As duas pacientes receberam alta com regressão parcial do déficit motor. O uso de pinçamento direto da aorta em comparação ao uso do dispositivo de oclusão endoaórtico foi semelhante em relação ao tempo de isquemia 84 ± 29 versus 87 ± 20 (P=0,4) e ao tempo de CEC 133 ± 40 versus 133 ± 39 (P=0,5). Conclusão: A incisão pelo 40 EICD permitiu bom acesso a valva Mitral. O uso de dispositivo de oclusão endoaórtico não aumenta o tempo de isquemia ou de CEC em relação ao pinçamento direto da aorta. As principais complicações são imputáveis a gravidade dos pacientes e eventualmente a curva de aprendizado do método.

Roberto Rocha e Silva; Renata Tosoni Rodrigues Ferreira; Vanessa Rejane Pesciotto; Elizeu de Sousa Santos; Ricardo De Mota Hospital Paulo Sacramento do grupo Intermédica, Instituto do Coração da HC-FMUSP Introdução:Tratamento minimamente invasivo da valva mitral pelo 40 Espaço Intercostal Direito (EICD) com apoio de vídeo. Relato de experiência de pinçamento direto da aorta ou uso de cateter de oclusão endoaórtico. Método: Entre 08/5/2012 a 9/9/2013, foram realizados 16 tratamentos de valva Mitral por cirurgia minimamente invasiva. Canulação de artéria e veia femural para Circulação Extra Corpórea (CEC). A incisão nos casos iniciais foi de 12 a 16 cm sobre o 40 EICD na linha axilar anterior. Nas mulheres foram feitas abordagens inframamarias. Secção do músculo peitoral maior e abertura do 40 EICD. Abertura do pericárdio 2 cm acima do nervo frênico expondo o coração com pontos de reparo. Vídeo inserido pelo 30 EICD. Entrada em CEC. Pinçamento direto da aorta e administração de cardioplegia anterógrada. Abertura do átrio esquerdo e tratamento da valva Mitral. Os procedimentos seguintes tiveram a incisão reduzida para cerca de 8 cm e utilizou-se em 5 casos, o dispositivo de oclusão endoaórtico. Seguiu-se com o fechamento do átrio esquerdo, implante de marca passo em ventrículo direito, saída de CEC e reposição volêmica. Retirada de cânulas e revisão de hemostasia. Drenagem de tórax. Fechamento convencional de toracotomia. Resultado:Foram realizadas 9 plastias e 7 trocas de valva Mitral. O tratamento Mitral foi adequado em todos os casos

TL - 02 Nova Técnica de Implante de Marcapasso Epicárdico com Acesso Atrial pelas Reflexões Pericárdicas em Pacientes com Acesso Venoso Limitado Roberto Costa, Katia Silva; Sávia Bueno, Wagner Tamaki, Marcelo Fiorelli, Cristiane Zambolim, Marianna Sobral, Paulo Gutierrez, Martino Martinelli Filho Instituto do Coração do HCFMUSP

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Introdução: Impedimentos para o uso da via endocárdica, em determinados pacientes, aumenta o risco cirúrgico e a complexidade do procedimento de implante de marcapasso convencional. Objetivo: Descrever o uso da abordagem epicárdica minimamente invasiva, com a utilização das reflexões pericárdicas, para implante de marcapasso dupla-câmara em pacientes com acesso venoso limitado. Métodos: No período de Jun/2006 a Nov/2011, 15 pacientes foram submetidos a implante de marcapasso epicárdico. Os procedimentos foram realizados através de uma abordagem minimamente invasiva, pelo acesso subxifóide, com posicionamento dos cabos-eletrodos assistido por fluoroscopia. A idade dos pacientes variou de 26 a 74 anos (46,4 ± 15,3), sendo 9 (60,0%) do sexo masculino. Treze dos 15 pacientes já eram portadores de marcapasso implantado previamente por um período médio de 18,5 ± 8,1 anos. A opção pelo uso da nova abordagem cirúrgica foi justificada pela presença de múltiplos cabos-eletrodos abandonados em 5 (33,3%) pacientes, obstrução venosa em 3 (20,0%), presença de fragmento de cabo-eletrodo retido após extração por infecção em 3 (20,0%), presença de vegetação em valva tricúspide ainda em tratamento em 2 (13,3%) e defeitos intracardíacos não corrigidos em 2 (13,3%), pacientes. Resultados: Todos os procedimentos foram realizados com sucesso, sem complicações intra-operatórias ou mortes. O tempo médio de duração da operação foi de 231,7± 33,5 minutos. O acesso ao topo do átrio direito pelo seio transverso foi possível em 12 (80%) pacientes. Nos outros 3 (20,0%), o eletrodo foi implantado no átrio esquerdo através do seio oblíquo, do recesso da veia cava superior ou do recesso da veia pulmonar esquerda. Não houve relato de dor torácica, febre ou outros sinais sugestivos de processo infeccioso no período pós-operatório. Os parâmetros de estimulação e sensibilidade dos cabos-eletrodos se mantiveram estáveis durante todo o período de seguimento de 36,8 ± 25,1 meses. Conclusões: O implante de marcapasso atrioventricular pelo acesso minimamente invasivo pode ser considerado uma abordagem segura, eficaz e reprodutível para pacientes que necessitam de estimulação fisiológica e que apresentam limitações à via endocárdica.

Fundamento- A fluxometria intra-operatória vem sendo realizada rotineiramente nos enxertos de nossos pacientes submetidos à revascularização do miocárdio. Por outro lado, estudos hemodinâmicos tardios de pacientes submetidos a revascularização do miocárdio tem revelado a possibilidade de fluxo entre artérias coronárias que receberam pontes sequenciais, mesmos quando estas pontes estão ocluídas em sua origem. Objetivo- Este estudo visa propor um modelo intra-operatório para avaliar o fluxo entre artérias coronárias, através da fluxometria entre pontes de safena. Método- Recentemente, pudemos verificar em dez pacientes operados sem circulação extra-corpórea e cujas lesões coronárias não eram críticas, grande refluxo pelas pontes de safena após as anastomoses distais. Para completar a revascularização, em nove deles, realizamos anastomoses proximais com pinçamentos laterais da aorta, que envolviam também outras pontes de safena para outras artérias coronárias com lesão maior. Nesse momento, antes de retirar essa exclusão lateral, verificamos a presença de fluxo entre as pontes de safena, que foi mensurado e registrado. No décimo paciente, em que anastomosamos uma ponte sobre a outra, esse fluxo entre as safenas também foi verificado, e sua medida foi feita antes de se retirar o bulldog da ponte que se originava da aorta. Resultados- Verificamos fluxos entre as artérias coronárias, através das pontes de safena, que variaram de 13 a 133 ml/ min (M= 42,1 ml/min), e índices de pulsatilidade entre 0,7 e 12,7 (M= 4,21). Não houve mortalidade nesse grupo e todos apresentaram boa evolução pós-operatória. Conclusão- Esse é um modelo que demonstra a possibilidade de haver fluxo inter-coronariano através de pontes de safena não valvuladas. Em raros casos em que os enxertos disponíveis durante a revascularização do miocárdio não tem comprimento suficiente para atingir os locais habitualmente utilizados (aorta ascendente, ou para realizar um enxerto composto), estas evidências oferecem ao Cirurgião uma fonte alternativa na obtenção de sangue arterial.

TL - 03 Avaliação de fluxo inter-coronariano através da fluxometria intra-operatória de pontes de safena.

Marcelo Biscegli Jatene, Gabriel Romero Liguori, Thais Fernandes de Camargo, Denise Akerman, Leonardo Augusto Miana, Juliano Gomes Penha, Luiz Fernando Caneo, Carla Tanamati.

TL - 04 Resultados em Curto Prazo da Técnica Warden para Correção da Conexão Anômala Parcial de Veias Pulmonares

Luis Alberto Oliveira Dallan; Luiz Augusto Lisboa; Luis Roberto Palma Dallan; Omar Mejia; Fernando Platania; Fabio Biscegli Jatene.

Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo INTRODUÇÃO: A técnica de Warden foi introduzida na tentativa de diminuir a incidência de disfunção do nó sinusal

Instituto do Coração da FMUSP

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e obstrução venosa após o reparo da conexão anômala parcial de veias pulmonares. Neste estudo, buscou-se relatar e avaliar os resultados imediatos de nossa experiência com a técnica de Warden. MÉTODOS: Foi realizado um estudo retrospectivo de 9 pacientes com drenagem anômala das veias pulmonares para a veia cava superior que tenham sido submetidos à técnica Warden durante o ano de 2011. Foram analisados ​​os registros médicos, relatórios cirúrgicos e resultados de exames complementares. RESULTADOS: Além da conexão anômala das veias pulmonares em veia cava superior, 5 (56%) pacientes também apresentaram uma comunicação interatrial do tipo ostium secundum ou forame oval patente e 2 (22%) apresentaram persistencia da veia cava superior esquerda. Uma paciente apresentava síndrome de Turner. Antes da cirurgia, 3 (33%) pacientes apresentaram algum tipo de distúrbio de condução: dois bloqueios de ramo direito e uma extra-sístole atrial. A média de idade no momento da cirurgia foi de 10,8±7,6 (min=2, max=29,7) anos, e a distribuição entre os sexos foi de 2:1, sendo a maioria do sexo masculino. Nenhum paciente foi submetido a reoperação ou evoluiu para óbito durante o período de follow-up. Após o reparo cirúrgico, um quarto paciente passou a apresentar bloqueio de ramo direito. O grau de dilatação das câmaras direitas melhorou significativamente, tanto em nível atrial (p=0,002) quanto ventricular (p=0,046), após a correção cirúrgica. Três (33%) pacientes apresentaram insuficiência tricúspide e/ou pulmonar pós-operatória. Nenhuma obstrução venosa foi resgistrada. CONCLUSÃO: Os resultados a curto prazo com a técnica Warden foram satisfatórios. Valvopatias e arritmias pósoperatórias, entretanto, parecem ser um risco, sendo necessário um maior tempo de seguimento para avaliar detalhadamente o impacto da técnica na morbi-mortalidade.

suporte circulatório são pós cardiotomia com dificuldade de saída de circulação extracorpórea (CEC), resgate após colapso cardiocirculatório e como ponte para transplante nos casos sem possibilidade de recuperação. OBJETIVO: Avaliar a utilização de ECMO como terapia de suporte circulatório em pacientes portadores de cardiopatia congênita em UTI cardiopediátrica. MÉTODOS: Análise retrospectiva dos dados de pacientes que utilizaram ECMO na UTI cardiopediátrica nos anos de 2011-2013 após treinamento de equipe multiprofissional. RESULTADOS: Neste período 14 pacientes utilizaram ECMO (8 neonatos; 5 lactente e 1 pré escolar); 12 casos (85,7%) pós cardiotomia e 2 casos (14,2%) pós parada cardíaca. 78,5% (11 casos) em crianças com fisiologia biventricular e 21,4% (3 casos) em univentriculares. A taxa de sobrevida global foi de 35,7%, sendo de 45,4% (6 casos) de sobrevida em biventriculares e óbito em todos os casos univentriculares. Complicações relacionadas ao método com desfecho desfavorável: 7,1% (1 caso) Hemorragia Intracraniana grau IV. Em 2 casos de assistência pós parada prolongada os pacientes evoluíram com morte cerebral (14,2%). Tempo médio em assistência: 3,9 dias (1 a 12 dias). CONCLUSÃO: A utilização da ECMO como suporte cardiocirculatório deve ser considerada nos casos refratários ao tratamento clínico. Apesar do grande risco de complicações relacionadas ao método, sua utilização permite a recuperação de alguns casos com alto risco de mortalidade sem o suporte circulatório mecânico. O treinamento multiprofissional é essencial para minimizar o risco de complicações. A avaliação de maior número de casos é essencial para melhor interpretação dos dados. Entretanto, fica evidente que o suporte em cardiopatias congênitas de fisiologia univentricular apresenta pior prognóstico quando comparado com aqueles com fisiologia biventricular.

TL - 05 A utilização de ECMO como Terapia de Suporte Circulatório em Pacientes Portadores de Cardiopatia Congênita em UTI Cardiopediátrica

TL - 06 MINITORACOTOMIA AXILAR: OPÇÃO ESTÉTICA E EFICIENTE PARA CORREÇÃO DE COMUNICAÇÃO INTERVENTRICULAR E INTERATRIAL EM LACTENTES E CRIANÇAS.

Fabiana Moreira Passos, Giovana Broccoli; Erica de Oliveira Paes; Carlos Regenga Ferreiro; Gilberto Scuciato; Marcelo Biscegli Jatene; Patrícia Marques Oliveira; Simone Rolim F. Pedra; Solange Coppola Gimenez; Ieda Biscegli Jatene.

AXILLARY MINITHORACOTOMY: AESTHETIC AND EFFICIENT OPTION FOR VENTRICULAR AND ATRIAL SEPTAL DEFECT REPAIR IN INFANTS AND TODDLERS.

INTRODUÇÃO: A ECMO (Extracorporeal Membrane Oxigenation) funciona como um dispositivo de suporte cardiopulmonar para quadros de falência cardíaca e/ou respiratória aguda e reversível, não responsivas aos tratamentos clínicos convencionais. Nas unidades de terapia intensiva (UTI) cardiopediátricas as indicações mais frequentes de

Luciana da Fonseca da Silva, Jose Pedro da Silva, Aida LR Turquetto, Sonia Franchi, Jose Francisco Baumgratz, Rodrigo Moreira Castro INTRODUÇÃO: O tratamento dos defeitos cardíacos apresenta progressiva redução da morbi-mortalidade, porém

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a cicatriz, sequela aparente do tratamento da comunicação interatrial (CIA) e interventricular (CIV), é definitiva. A abordagem por minitoracotomia axilar é opção para correção destes defeitos com possível melhor estética e baixo custo, evita a região de crescimento da mama. Desde outubro de 2011, empregamos esta técnica para correção de CIV, CIA e defeitos associados em 80 pacientes. OBJETIVOS: Mostrar os resultados em pacientes consecutivos submetidos à técnica para correção de defeitos diversos. Avaliar a segurança e eficácia deste tipo de procedimento. Avaliar o resultado estético obtido. MÉTODOS: Dados clínicos peri-operatórios de 80 pacientes submetidos à minitoracotomia axilar foram analisados, avaliando a eficácia e resultado estético da incisão. Os dados dos 25 pacientes iniciais foram comparados com dados de 25 pacientes (pareados para sexo, idade e diagnóstico) submetidos à correção de defeitos cardíacos semelhantes por esternotomia mediana. RESULTADOS: A correção dos defeitos via axilar foi factível nos 80 pacientes em que foi proposto, inclusive em lactentes, com grande satisfação estética. Destes, 24 tiveram diagnóstico de CIV isolada ou associada a CIA, 7 apresentavam CIA com drenagem anômala parcial de veias pulmonares. A idade variou de 5 meses a 13 anos. Na comparação dos 25 pacientes iniciais, os dados peri-operatórios foram semelhantes, exceto pelo menor uso de hemoderivados no grupo axilar (6/25) x controle (13/25), com diferença estatística (p=0,04). A canulação da aorta e veias cavas foi realizada através da incisão principal, cujo tamanho variou de 3 a 5 cm no grupo axilar, com resultado estético excelente. CONCLUSÕES: A minitoracotomia axilar foi eficaz, permitiu correção do defeito cardíaco semelhante à esternotomia mediana, com resultado estético mais satisfatório e menor necessidade de transfusão sanguínea, podendo ser utilizada com segurança em lactentes.

por Lalezari et al, existe uma diminuição da musculatura lisa no tronco pulmonar (TP) que poderia explicar a dilatação do TP. Com o objetivo de se evitar a dilatação da neoaorta e insuficiência aórtica, nós estamos propondo a realização da cirurgia de Dupla Translocação Truncal (DTT) para se corrigir TGA. DESCRIÇÃO DA TÉCNICA CIRÚRGICA: Após realização de toracotomia mediana transesternal, é instalado circulação extracorpórea (CEC) com hipotermia leve e proteção miocárdica com solução cardioplégica sanguinea potássica administrada a cada 20-30 minutos. O tronco aórtico (TA) é retirado do ventrículo direito (VD) incluindo a valva aórtica e as artérias coronárias, o TP é retirado com a valva pulmonar do ventrículo esquerdo (VE), transloca-se o TA para o VE. É realizado fechamento do orifício de retirada do TA com pericárdio autólogo fresco e posteriormente o TP translocado para este orifício. PACIENTES: No período de janeiro de 2011 a junho de 2013, quatro crianças foram submetidas a DTT com idade média de 30,2 dias (4-65), pêso médio de 3,6 kg (2,6-4,9). Duas eram portadoras de TGA com septo ventricular íntegro, uma TGA com CIV e outra TGA tipo Taussig-Bing. O tempo médio de circulação extracorpórea foi de 229 min (152-365) e o tempo médio de anoxia 156,2 (104-288). Em duas crianças foi necessário secção de um dos ramos pulmonares junto ao TP, anteriorização do TP e do ramo pulmonar e sutura ao VD. Foi realizado autoimplante da coronária direita em uma criança e autoimplante das 2 coronárias em outra. RESULTADOS: Houve um óbito cirúrgico (25%), o seguimento após a alta das outras três crianças mostrou que estão em classe funcional I (NYHA), eletrocardiograma com ritmo sinusal e ausência de isquemia miocárdica. O exame ecocardiográfico revelou função normal dos ventrículos direito e esquerdo e ausência de regurgitação das valvas pulmonar e aórtica. CONCLUSÃO: Acreditamos que a DTT pode reduzir a dilatação da neoaorta porque na DTT ocorre uma correção anatômica completa em corações com TGA, colocando o tronco aórtico com a valva aórtica na via de saída do ventrículo esquerdo e o tronco pulmonar com a valva pulmonar na via de saída do ventrículo direito.

TL - 07 Cirurgia de Dupla Translocação Truncal para correção da Transposição das Grandes Artérias, descrição da técnica e resultados iniciais. Gláucio Furlanetto; Beatriz Furlanetto; Sandra R C Henriques; Eduardo M Teixeira; Carolina M G Porto; Maria Elisa M Albrecht

TL - 08 BANDAGEM AJUSTÁVEL DO TRONCO PULMONAR X : E S T R E S S E D E PA R E D E V E N T R I C U L A R ASSOCIADO À ATIVAÇÃO DA GLICOSE-6-FOSFATO DESIDROGENASE É NORMALIZADO PELA SOBRECARGA SISTÓLICA INTERMITENTE EM CABRITOS JOVENS

Beneficência Portuguesa de São Paulo INTRODUÇÃO: A operação de Jatene (OJ) é a cirurgia de escolha para se corrigir a Transposição das Grandes Artérias (TGA). No seguimento tardio podem ocorrer algumas complicações: arritmia, disfunção ventricular, estenose de ramo pulmonar, obstrução coronariana, dilatação da neoaorta e insuficiência da neovalva aórtica. Segundo estudos realizados

Renato Samy Assad, Acrisio S. Valente, Miriam Helena Fonseca Alaniz, Maria Cristina Donadio Abduch, Gustavo

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José Justo da Silva, Fernanda dos Santos Oliveira, Luiz Felipe Pinho Moreire, Jose Eduardo Krieger.

animais foram sacrificados para avaliação morfológica e da atividade da G6PD no miocárdio. Resultados: Houve um aumento de 130.8% na massa do VD do grupo 96 horas, comparado ao grupo Zero hora (p<0.0001). A relação volume/massa e o estresse de parede do VD observado nos grupos 24, 48 e 72 horas foram associados ao aumento da atividade da G6PD (r = 0,47 e 0,42; p = 0,01 e 0,03, respectivamente). Houve recuperação destes parâmetros no grupo 96 horas, quando comparado aos valores basais. Não houve diferenças significativas na atividade da G6PD do septo ventricular e ventrículo esquerdo. Conclusões: A atividade miocárdica da G6PDH está associada a alterações de volume e estresse de parede do VD. Este estudo sugere que a sobrecarga sistólica intermitente para o preparo rápido do ventrículo subpulmonar de cabritos jovens pode amenizar as alterações do metabolismo energético do miocárdio, manobra que minimiza o acúmulo de produtos glicolíticos e radicais livres, sabidamente relacionados à falência miocárdica.

Instituto do Coração HCFMUSP, São Paulo, SP, BRASIL. Objetivo: A bandagem tradicional do tronco pulmonar (TP) promove o aumento da atividade da enzima Glicose-6-Fosfato Desidrogenase (G6PD) e, consequentemente, maior produção de NADPH e radicais livres. Este estudo avalia a mecânica miocárdica e a cinética da atividade da G6PD durante a sobrecarga sistólica intermitente do ventrículo subpulmonar (VD) de cabritos jovens. Método: 30 cabritos jovens foram divididos em 5 grupos, de acordo com o tempo de sobrecarga sistólica intermitente do VD (Zero, 24, 48, 72 e 96 horas). A sobrecarga sistólica do VD (70% da pressão sistêmica) de 12 horas foi alternada com igual período de descanso, com dispositivo de bandagem ajustável do TP. Avaliações ecocardiográficas e hemodinâmicas foram feitas diariamente. Após cumprir o tempo de cada grupo, os

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P - 01 Valva aórtica tetracúspide. Relato de caso e revisão de literatura.

circulação extra-corpórea com canulação de aorta e veia cava inferior e veia cava superior. Com hipotermia moderada a 28C foi realizado o pinçamento da aorta. Após aortotomia oblíqua foi visualizada valva aórtica tetracúspide, sem diagnóstico prévio pelo ecocardiograma transtorácico. Administrada cardioplegia nos óstios coronários, seguida de administração por via retrógrada por cânula posicionada no seio coronário. A valva aórtica apresentava três cúspides de tamanho equivalente e uma cúspide menor. Após excisão completa da valva foi realizada a substituição por prótese biológica de pericárdio bovino (Labcor Dokimus 23 mm). O tempo de CEC e de pinçamento aórtico foram respectivamente 65 min e 54 min. A evolução pós-operatória foi sem intercorrências e a paciente recebeu alta no quinto dia de pós operatório. Discussão: Desde o primeiro caso descrito em 1862(3, 4), menos de 200 casos foram descritos até hoje na literatura mundial(5). Feldman et al em 1990 (1)relataram incidência de apenas 8 casos de VATC em mais de 60.000 exames de ecocardiografia analisados, configurando incidência de 0,013%. Muitas vezes, devido à baixa incidência desta alteração anatômica, o ecocardiograma não é capaz de dar o diagnóstico definitivo da anomalia. Assim como no caso descrito por Denker e Stagmo(6), nosso paciente também não obteve diagnóstico pré-operatório pela ecocardiografia. Provavelmente o caráter incomum desta variação anatômica leva ao seu baixo diagnostico pelos métodos de imagem. A associação com outras alterações anatômicas deveria motivar investigação clínica mais apurada nos casos em que este diagnostico fosse feito. Conclusão: A presença de valva aórtica tetracúspide, apesar de rara, pode estar associada a outras mal-formações cardíacas. Desta forma, é importante que os médicos busquem seu diagnóstico pré-operatório.

Guilherme de Menezes Succi, José Ernesto Succi, Camila de Menezes Succi, Marcelo Melro Mendonça, Fabiana Moreira Passos Succi, Carlos Edson Campos Cunha Filho Curso de Medicina da Faculdade São Leopoldo Mandic Introdução: Valva aórtica tetracúspide é uma alteração anatômica rara, com poucos casos descritos na literatura. Sua incidência varia de 0,008% a 0,033%(1). Podem aparecer como malformação cardíaca isolada, mas em alguns casos são acompanhadas de outras alterações como anomalias de coronárias, comunicação interatrial ou comunicação interventricular(2). Descrevemos caso de paciente de 49 anos com diagnóstico de insuficiência aórtica que teve a identificação da anomalia valvar apenas no intra-operatório. Relato de caso: Identificação: VMO, 49 anos, branca, natural de Alagoas, procedente de São Paulo há 33 anos, divorciada, 1° grau incompleto. Apresenta queixa de cansaço aos moderados esforços há 8 meses, com piora para pequenos esforços há 2 meses. HPMA: Paciente com diagnóstico prévio de lesão valvar aórtica (insuficiência aórtica) há 12anos, em exame admissional seguindo acompanhamento ambulatorial com cardiologista. Assintomática até há 8 meses, quando iniciou quadro de cansaço e dispnéia aos moderados esforços, progredindo para os pequenos esforços há 2 meses, associado a vertigem e palpitações taquicárdicas rítmicas com duração inferior a 10minutos - relacionadas ao esforço ou ao estresse emocional. Nega dor torácica, síncope, tosse, expectoração, febre ou emagrecimento no período. Antecedentes Pessoais / Comorbidades: HAS em uso de losartan 50mg/dia. Osteopenia em uso de alendronato de sódio 70mg 1x/semana. 2G2PN0A. Nega tabagismo, etilismo. Realizou ecocardiograma transtorácico que mostrou insuficiência aórtica de grau importante com disfunção ventricular esquerda de grau moderado. Cinecoronariografia revela coronárias normais, sem obstruções. A paciente foi submetida a tratamento cirúrgico para troca da valva aórtica. Com a paciente sob anestesia geral e acesso através de esternotomia mediana foi realizada instalação de

REFERÊNCIAS 1 - Válvula aórtica quadricúspide - Casuística de 10 anos e revisão da literatura. Sofia Gouveia, José Diogo Ferreira Martins, Glória Costa, Filipa Paramés, Isabel Freitas, Mónica Rebelo, Conceição Trigo, Fátima F. Pinto. Rev Port Cardiol. 2011;30(11):849---854. 2 - Quadricuspid Aortic Valve with Ascending Aortic Aneurysm: A Case Report and Histopathological Investigation. Tsukioka K, et al. Ann Thorac Cardiovasc Surg. 2011;17(4):418-21.

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das coronárias dos enxertos cardíacos de ambos os grupos. Conclusões: O modelo experimental de indução de coronariopatia com o emprego de nanopartículas de colesterol em coelhos mostrou-se eficaz na indução da vasculopatia, sendo mais intensa no coração transplantado, podendo ser extremamente útil no estudo da doença vascular do enxerto.

3 - The quadricuspid aortic valve: a comprehensive review. Tutarel O. J Heart Valve Dis. 2004 Jul;13(4):534-7. 4 - Incidence, description and functional assessment of isolated quadricuspid aortic valves. Feldman JB, et al. Am J Cardiol. 1990 Apr 1;65(13):937-8. 5 - Quadricuspid aortic valves. Timperley J, Milner R, Marshall AJ, Gilbert TJ. Clin Cardiol. 2002 Dec;25(12):548-52.

P - 03 Tratamento cirúrgico da trombose de prótese mecânica mitral em puérpera

6 - Quadricuspid aortic valve not discovered by transthoracic echocardiography. Dencker M, Stagmo M. Cardiovasc Ultrasound. 2006 Nov 7;4:41.

Autores: Samuel Padovani Steffen; Pablo Maria Alberto PomerantzeffI; Carlos Manuel de Almeida Brandão; Gisele Aparecida Lapenna; Camilo Rodriguez Camilo Rodriguez; Fábio Biscegli Jatene.

P - 02 Doença Vascular do Enxerto com a infusão endovenosa de nanoemulsão artificial. Estudo Experimental.

Instituto do Coração do HCFMUSP

AUTORES: Dolma Ribeiro de Farias; Tiago Wanderley Diniz Chamel; Leonardo Ervolino Corbi; Gabriel Erra Ramos; Igor Silva Fernandes Machado; Pedro Queiroz Ferreira Tito; Raif Restivo Simão; Rômulo dos Santos Sobreira Nunes; Domingos Dias Lourenço Filho; Alfredo I. Fiorelli; Noedir A.G. Stolf; Fabio B. Jatene.

Introdução: O manejo clínico das pacientes grávidas e puérperas portadoras de próteses cardíacas mecânicas é difícil e muitas vezes desafiador. Relatamos o caso de uma puérpera que apresentou trombose da prótese mecânica mitral, com necessidade de tratamento cirúrgico. Relato do caso: Paciente SSG, 24 anos, portadora de cardiopatia reumática desde a infância, com três cirurgias de troca valvar mitral prévias, sendo a última há seis anos, com implante de prótese mecânica. Venho encaminhada para o nosso serviço no segundo dia pós-parto cesáreo devido a edema agudo pulmonar súbito. Ao ecocardiograma visto imagem hipodensa, revestindo os folhetos da prótese na face atrial, de limites imprecisos, caracterizando trombose importante de prótese mecânica mitral. Foi optado pelo tratamento cirúrgico. Após preparo habitual e estabelecimento da circulação extracorpórea (CEC), encontrado vários trombos antigos e recentes, tanto na face atrial, quanto na face ventricular. Não havia alterações na prótese. Realizado trombectomia atrial e ventricular esquerda, sem intercorrências, preservando a prótese. A paciente teve boa evolução pós-operatória. Discussão: Todas as próteses cardíacas mecânicas são trombogênicas e requerem anticoagulação para evitar fenômenos tromboembólicos. O período gestacional se torna crítico nesta situação uma vez que produz um estado de hipercoagubilidade natural. O uso da warfarina em mulheres grávidas no primeiro trimestre resulta em alto risco de aborto e de malformações fetais, levando a maioria dos serviços a preconizar o uso de heparina não fracionada nas primeiras 6 a 12 semanas. Apesar da heparina ser mais segura para uso na gestação, existem estudos que mostram uma maior taxa de fenômenos tromboembólicos quando usadas durante o período gestacional. No presente caso a gestação transcorreu normalmente, sem qualquer intercorrência fetal ou materna

Instituição: Instituto do Coração da Universidade de São Paulo/Brasil. Fundamento:No transplante cardíaco a doença vascular do enxerto é uma complicação insidiosa, caracterizada por inflamação perivascular persistente com hiperplasia intimal e representa o principal fator limitante do transplante em longo prazo. Diferentes estudos experimentais tem procurado desenvolver um modelo que reproduza a doença vascular após o transplante. Objetivo: Avaliar o comportamento de doença vascular do enxerto nos vasos coronários e o grau de hiperplasia intimal no coração transplantado e nativo de coelhos que receberam nanopartículas de LDE. Material e Método: Dez e um coelhos machos da raça Nova Zealand (Brancos) com peso médio de 3,4±0,6kg e Dez machos (Vermelhos) com peso médio de 2,7±0,5kg, sendo que os brancos foram os receptores de enxertos cardíacos dos coelhos vermelhos. Os animais receptores foram divididos em dois grupos. Os animais foram tratados com 3 ml de solução salina administrada por via intravenosa durante o mesmo período. Todos os animais foram alimentados com ração enriquecida de 0,5% de colesterol e receberam 10mg/kg/ dia ciclosporina A. Após o período experimental, os coelhos foram sacrificados para análise. O protocolo do estudo foi aprovado pelo Comitê de Ética em Experimentação Animal da Universidade de São Paulo. Resultados: Uma tabela apresenta expressa a morfometria

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e não houve descontinuidade ou uso irregular da terapia antitrombótica proposta. Apenas no segundo dia pós-parto que se iniciou o quadro clínico, sendo feito o diagnóstico de trombose de prótese. Pacientes grávidas portadoras de próteses mecânicas que apresentam trombose de prótese tem como opção terapêutica a fibrinólise, o tratamento cirúrgico ou a terapia anticoagulante. A escolha do melhor tratamento vai depender, principalmente, do estado hemodinâmico da paciente no momento da avaliação, além das características do trombo ao ecocardiograma. Neste caso foi indicado o tratamento cirúrgico, com ótimo resultado final. Conclusão: O período gestacional é crítico para pacientes portadoras de próteses mecânicas, tanto pelo maior risco trombogênico, quanto pelos efeitos materno-fetais deletérios dos anticoagulantes. A trombose de prótese é um fenômeno grave, de risco elevado e o tratamento depende basicamente do quadro clínico e das características ecocardiográficas do trombo.

reduzindo o seu diâmetro de 22 mm para 4,2 mm (13 FR). Discussão: Estudos experimentais de válvula de poliuretano publicados mostraram bom desempenho hemodinâmico e baixa incidência de calcificação. O stent expansível tem vantagens porque é possível alterar o seu diâmetro, utilizando cateter balão, acompanhando o desenvolvimento da criança. Conclusão: Trata-se de projeto sustentável que beneficia o Paciente, porque é: durável, expansível, implantado por catéter; o Meio ambiente: porque não manipula tecido animal nem soluções químicas; a Economia: porque tem baixo custo; O Cirurgião: porque o implante tem acesso transcatéter; a Sociedade: porque é produto avaliado pelo método científico. P - 05 Apresentando a Oxigenação por Membrana Extracorpórea (ECMO) para Profissionais de Saúde: a Importância de um Curso Teórico Básico Marcelo Biscegli Jatene, Gabriel Romero Liguori, Leonardo Augusto Miana, Juliano Gomes Penha, Luiz Fernando Caneo, Carla Tanamati.

P - 04 Novo protótipo de stent válvula expansível de poliuretano, para implante pela técnica transcateter.

Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Maluf M*, Gomes W*, Lage L*, Mercuri L*, Obradovic M**, Bregulla R**, Grathwohl H**

INTRODUÇÃO: A equipe multidisciplinar é essencial para um serviço de ECMO de alta qualidade. No entanto, poucos profissionais de saúde têm algum conhecimento sobre ECMO e, além disso, existem grandes discrepâncias entre o nível de conhecimento destes profissionais. Assim, avaliamos o impacto de um curso teórico básico em ECMO no ganho de conhecimento de diferentes profissionais de saúde. MÉTODOS: Um curso teórico de seis horas básicas sobre ECMO foi ministrado a um público heterogêneo, formado por 12 estudantes de medicina, 10 enfermeiros, 4 perfusionistas e 4 médicos. Foram incluídos no curso os seguintes tópicos: 1) conceito de ECMO; 2) cenários de uso; 3) aspectos do circuito; 4) as diferenças entre ECMO pulmonar e cardíaca; 5) gestão de pacientes em ECMO; 6) aspectos da canulação; 7) complicações; 8) conceito de E-CPR; e 9) a importância da equipe multidisciplinar. Questionários de auto-avaliação, graduando de 1 a 5 o nível de conhecimento sobre os temas referidos, foram realizados imediatamente antes e após o curso. RESULTADOS: Vinte e seis (76,6%) questionários foram preenchidos. Os três temas mais claros antes do curso eram a importância da equipe multidisciplinar (2,96±1,36), o conceito de ECMO (2,57±1,27) e cenários de uso (2,39±1,2) , enquanto que o três temas menos claros eram o conceito de E-CPR (1,65±0,93), gestão de pacientes em ECMO (1,87±1,01) e aspectos da punção (1,91±1,12) . Houve uma importante, embora não significativa, discrepância entre o

* Universidade Federal de São Paulo – Brazil ** Bentley InnoMed – Hechingen - Germany Introdução: Na procura de novos materiais bioestáveis, biocompatíveis, resistentes a fadiga e com baixo índice de calcificação, tromboembolismo e infecção, o poliuretano constitui uma alternativa viável, para a manufatura da próteses cardíacas. Objetivos: Desenvolver um protótipo de stent válvula de poliuretano, para implante transcateter em pacientes pediátricos, que possa ser expandido acompanhando o crescimento do paciente. O diâmetro da stent válvula expansível, pode ser dimencionado mediante a utilização de cateter balão. Material / Métodos – Manufatura do Prototipo: Sera construído um stent válvula expansível de cromo cobalto, revestido por membrana de politetrafluoroetileno com diâmetro de 22 mm. Um suporte de aço inoxidável de geometria cilíndrica com diâmetro de 20 mm, cuja extremidade superior apresenta o formato dos seios de valsalva de uma valva sigmoidea. Preparo do poliuretano para a formação das cúspides valvares. O stent de 22mm é acoplado ao suporte de 20mm e realizado o procedimento de aplicação do poliuretano, para a construção de três finos folhetos da válvula. As prótese liberadas após os testes in vitro, são submetidas a clipagem dentro de catéter balão,

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nível de conhecimento das diferentes categorias profissionais antes do curso (p=0,157). Após o curso, um ganho de conhecimento significativo foi observado em todos os tópicos (p<0,001). Perfusionistas apresentaram menor ganho do que outros participantes (p=0,05). No final, houve uma homogeneização do nível de conhecimento entre o público (p<0,001). CONCLUSÃO: Um curso teórico básico ECMO é importante, não só para difundir o conhecimento sobre ECMO, mas também para nivelar diferentes profissionais para futura formação avançada, especialização e formação de uma equipe institucional integrada.

os casos, principalmente quando utilizado o afastador de partes moles. Os tempos médios de isquemia e de CEC foram respectivamente 89 ± 21 minutos e 118 ± 27 minutos. Todos tiveram boa evolução e receberam alta hospitalar com prótese implantada normofuncionante. A incisão não passou de 10 cm em nenhum caso, gerando satisfação dos pacientes em relação à estética. Houve uma complicação tardia: paciente apresentou importante acesso de tosse no 140 pós operatório (PO) com abaulamento da incisão. Diagnosticada hérnia incisional com integridade dos planos superficiais e do músculo peitoral maior. Reoperado eletivamente com reaproximação das costelas e fechamento por planos. Recebeu alta no 30 PO com boa evolução tardia. Este evento de tosse poderia, no caso de uma esternotomia, ter levado a deiscência total e possível mediastinite com alta morbimortalidade. Conclusão: A incisão pelo 20 EICD permitiu bom acesso a valva aórtica, se mostrando um procedimento seguro. A incisão foi menor e mais estética que a esternotomia clássica. A complicação incisional foi de fácil correção provavelmente evitando uma mediastinite.

P - 06 TRATAMENTO DE VALVA AÓRTICA POR MINITORACOTOMIA PELO SEGUNDO ESPAÇO INTERCOSTAL: Relato de experiência de serviço. Roberto Rocha e Silva; Vanessa Rejane Pesciotto; Ricardo De Mota; Elizeu de Souza Santos Hospital Paulo Sacramento do grupo Intermédica, Instituto do Coração da HC-FMUSP

P - 07 Estimulação atrial epicárdica com cabos-eletrodos de fixação ativa e liberação de corticoide: avaliação das alterações macroscópicas e microscópicas.

Introdução: O tratamento clássico da valva aórtica é por esternotomia mediana apresentando até 4% de mediastinite. O acesso minimamente invasivo pelo 20 Espaço Intercostal Direito (EICD) pode evitar esta grave complicação e promover uma cicatriz menor e mais estética. Relatamos nossa experiência com este acesso. Método: Entre 03/12/2012 a 27/9/2013, realizamos 13 trocas de valva aórtica por cirurgia minimamene invasiva. A incisão na pele foi de 6 a 10 cm, secção do músculo peitoral maior e abertura do 20 EICD. Ligadura e secção da Mamária Direita. Desinserção da 30 costela junto ao esterno e colocação do afastador. Nos últimos casos, foi utilizado o afastador de partes moles. Abertura do pericárdio próximo a linha mediana expondo o coração com pontos de reparo. Canulação da Aorta o mais distal possível. Passagem de cânula venosa única pelo 50 ou 60 EICD e introdução na aurícula direita. Entrada em Circulação Extra Corpórea (CEC). Pinçamento direto da aorta e administração de cardioplegia anterógrada por punção ou nos óstios coronarianos após abertura transversa da aorta. Ventrículo esquerdo aspirado por cânula inserida pela veia pulmonar esquerda. Troca convencional da valva aórtica. Fechamento da aorta, implante de marca passo em ventrículo direito, saída de CEC e reposição volêmica. Retirada de cânulas e revisão de hemostasia. O orifício de drenagem foi o mesmo utilizado pela cânula venosa. Fechamento convencional de toracotomia. Resultados: A troca de valva aórtica ocorreu sem intercorrências e com boa exposição da aorta em todos

Roberto Costa, Katia Silva, Sávia Bueno, Wagner Tamaki, Marcelo Fiorelli, Cristiane Zambolim, Marianna Sobral, Paulo Gutierrez, Martino Martinelli Filho Instituto do Coração do HCFMUSP Introdução: As vantagens inquestionáveis da via de acesso venosa para estimulação cardíaca artificial tornaram as abordagens epicárdicas opções pouco utilizadas. Desse modo, não existem opções de eletrodos para implante na superfície atrial. Objetivos: Realizar o implante de eletrodo de fixação ativa com liberação de corticoide no epicárdio atrial direito (AD) de animais de experimentação, para avaliar a efetividade das condições de estimulação e de sensibilidade e as alterações macro e microscópicas no local de contato e no trajeto do eletrodo. Métodos: Foram operados 10 porcos da raça Large White. Por toracotomia ântero-lateral esquerda, os eletrodos Medtronic 4968-35 e 4076-52 foram implantados, respectivamente, na parede livre do ventrículo esquerdo e na porção medial do AD. O acesso ao AD foi obtido pelo seio transverso. As condições de estimulação e de sensibilidade do eletrodo atrial, nas configurações uni e bipolar, foram avaliadas no intra-operatório, pós-operatório (PO) imediato, no 7º e 30º

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PO. Após 30 dias de sobrevida, os animais foram reoperados por toracotomia longitudinal mediana para análise das aderências pericárdicas e das condições histopatológicas da junção entre o eletrodo e o epicárdico. As aderências foram classificadas de acordo com sua intensidade (sem aderência, frouxa, intermediária ou firme). Resultados: As condições de estimulação e sensibilidade mantiveram-se estáveis ao longo do estudo e não houve deslocamento dos eletrodos. Foram encontradas aderências em todos os animais e em todas as regiões avaliadas, sendo frouxas ou intermediárias nas regiões que não tiveram contato com os eletrodos e firmes nas regiões de contato. Observouse resposta inflamatória crônica inespecífica nas regiões de contato. Quando comparado à região controle, o contato com o eletrodo provocou espessamento significativo em três das regiões estudadas: no local onde os eletrodos atrial (P=0,043) e ventricular (P=0,002) estavam implantados e na parede posterior da artéria pulmonar (P=0,003) que se manteve em contato com o eletrodo atrial. Conclusões: A estimulação atrial epicárdica, com eletrodo de fixação ativa e liberação de corticoide, mostrou-se segura e efetiva. A única alteração encontrada foi aderência pericárdica. A cicatriz na região de implante do eletrodo AD mostrou-se semelhante à encontrada para o eletrodo ventricular.

à dispneia há seis meses e imagem de cardiomegalia a esclarecer. Ao ecocardiograma evidenciou-se acinesia apical, associado à pseudoaneurisma medindo 74x32 mm. Realizado cineangiocoronariografia, sem lesões obstrutivas. Encontrava-se hemodinamicamente estável em ventilação espontânea. Os marcadores de necrose miocárdica eram normais. No intraoperatório visualizou-se múltiplas aderências pericárdicas e grande dilatação aneurismática no ápice ventricular esquerdo. Foi estabelecida circulação extracorpórea (CEC) com hipotermia a 28 graus e cardioplegia sanguínea fria anterógrada a cada 20 minutos. Feito ressecção do pseudoaneurisma e fechamento do colo com patch de pericárdio bovino. Retornou bem de CEC e a evolução foi satisfatória. A análise anátomo patológica confirmou o diagnóstico de pseudoaneurisma, porém com uma característica relacionada ao lúpus: vasculite linfocítica. Discussão: O LES sabidamente pode causar alguma forma de doença cardíaca, provavelmente por causa da deposição de imunocomplexos e ativação do complemento. A agressão pode ocorrer como pericardite, miocardite, endocardite e coronariopatia. Existem relatos na literatura de pacientes portadores de LES com lesões cardiovasculares graves, como aneurismas de aorta, dissecção aórtica e coronariopatia, porém estavam associados ao uso de corticosteroides, contribuindo ao desenvolvimento da aterosclerose. Neste caso a paciente não fazia uso da terapia imunossupressora, contribuindo para a hipótese de que a etiologia foi agressão lúpica. Após revisão, não encontramos nenhum relato de paciente com LES e pseudoaneurisma ventricular. Acreditamos que os mesmos fatores causais da outras formas de doença cardíaca foram os responsáveis pela formação do pseudoaneurisma. Conclusão: Este provavelmente é o primeiro relato de uma paciente lúpica, sem doença coronariana, com pseudoaneurisma ventricular. O mecanismo fisiopatológico provavelmente se assemelha ao já existente da agressão cardíaca lúpica.

P - 08 PSEUDOANEURISMA DE VENTRÍCULO ESQUERDO EM PACIENTE LÚPICA - LEFT VENTRICULAR PSEUDOANEURYSM IN A LUPIC PATIENT Samuel Padovani Steffen, Pablo Maria Alberto Pomerantzeff, Carlos Manuel de Almeida Brandão, Gisele Aparecida Lapenna, Fábio Biscegli Jatene, Elinthon Tavares Veronese. Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo

P - 09 Drenagem anômala total das veias pulmonares: uma rara apresentação

Introdução: Os pseudoaneurismas de ventrículo esquerdo ou falsos aneurismas são formados após ruptura da parede miocárdica, tamponada por camadas de organização trombótica e de pericárdio, sem a presença de músculo cardíaco. É uma condição clínica rara e potencialmente fatal. A apresentação clínica é variável e normalmente ocorre como complicação mecânica pós-infarto miocárdico transmural. Neste relato apresentamos um caso de pseudoaneurisma de ventrículo esquerdo em uma paciente portadora de Lúpus Eritematoso Sistêmico (LES), sem doença coronariana associada. Relato do caso: Paciente EAF, 30 anos, com diagnóstico de LES há quatro anos, sem tratamento, encaminhada devido

Guilherme Ricardo Nunes Silva, Nathalie Jeanne Magioli Bravo-Valenzuela Introdução: A drenagem anômala total das veias pulmonares (DATVP) é uma cardiopatia congênita rara e grave que geralmente não se acompanha de outros defeitos cardíacos. O tratamento desta cardiopatia é cirúrgico e deve ser indicado assim que realizado o diagnóstico. Descrição do caso: Recém-nascido do sexo masculino nasce após 38 semanas de gestação com desconforto respiratório precoce

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e cianose, além de apresentar microftalmia, microretrognatia, fenda palatina, criptorquidia e micropênis. Cariótipo com banda G normal (46XY). Internado na UTI neonatal foi realizado radiografia de tórax que evidenciou aumento da área cardíaca, com imagem em “boneco de neve”. O ecocardiograma inicial demonstrou forame oval patente com shunt direita-esquerda, comunicação interventricular de via de entrada com extensão para via de saída (7mm), valvas atrioventriculares no mesmo plano, canal arterial pérvio e hipertensão arterial pulmonar. Evoluiu com piora da cianose, que indicou novo ecocardiograma, onde foi visualizada estrutura no átrio esquerdo que levantou a hipótese diagnóstica de cor triatriatum e, em um ecocardiograma posterior, de drenagem anômala parcial das veias pulmonares, sendo indicada correção cirúrgica. O cateterismo cardíaco préoperatório evidenciou DATVP esquerdas, ambas estenosadas e atresia das veias pulmonares direitas. O paciente foi então submetido à cirurgia que se resumiu a realizar a plastia das veias pulmonares esquerdas e implantá-las no átrio esquerdo, mantendo uma comunicação interatrial residual. Na evolução, as veias pulmonares reestenosaram e foi tentada a dilatação sem sucesso, ocasionando o óbito. Conclusão: O diagnóstico da DATVP possui algumas peculiaridades e ainda constitui um desafio, principalmente quando associada a outras anomalias cardíacas. Nessa situação, além do ecocardiograma, deve ser considerada a solicitação da angiografia por tomografia computadorizada ou cateterismo cardíaco para diagnóstico morfológico de certeza da malformação. O prognóstico da DATVP na presença de obstrução é bastante reservado, principalmente quando associado a outras anomalias cardíacas, como no caso descrito. A presença de estenose das veias pulmonares torna mais complexa a correção cirúrgica e, conseqüentemente, piora a evolução clínica do paciente.

Em nosso meio restaram poucas prótese do modelo de Gaiola implantadas, sendo raro na pratica diária. Abaixa frequência desta válvula se deve ao caráter evolutivo da doença valvar, as complicações relacionadas ao uso de anticoagulante e pela deterioração da prótese, portanto a experiência com a válvula de bola é importante para o enriquecimento da pratica médica. Relato do Caso: Paciente branco, 59 anos com antecedente de cirurgia para implante de prótese mecânica de Gaiola em posição aórtica em julho de 1979 e acidente vascular encefálico há 2 anos sem sequela motora focal e evolução de 6 meses de Insuficiência Cardíaca Congestiva CF III NYHA. Devido a piora do quadro clinico com mudança de classe funcional de grau I para III o mesmo foi encaminhado tratamento cirúrgico de dupla troca mitral e aortica. Ecocardiograma: Diâmetros: Ventrículo esquerdo sistólico 56 mm / diastólico 35 mm, Aorta: 4,3 mm; Atrio esquerdo de 47 mm; VSF:45 ml; FE: 0,74; Pressão sistólica em Arteria Pulmonar 46 mmHg; Válvula Aórtica com presença de Protese de gaiola e gradiente transvalvar sistólico máximo de 88 mmHg e médio de65mmHg; Válvula Mitral com fusão comissural e abertura em Domus e presença de Insuficiência de grau importante. Cirurgia: No ato cirúrgico foi realizada a substituição da prótese de Bola e da valva nativa Mitral por Próteses Mecânicas de duplo folheto St jude Medical. Como achados cirúrgicos intra operatório tivemos: coração em ritmo sinusal, a área cardíaca de +++/4 globalmente aumentada, a Artéria Pulmonar dilatada ++/4 e tensa e Aorta na sua porção ascendente dilatada ++/4 com espessura de parede afinada. Procedimento teve duração total de três horas e quinze minutos com 115 minutos de total de circulação extra corpórea (CEC) e 95 de pincamento aórtico. Conclusão: Os principais relatos de complicações com troca da válvula de Gaiola referem se a deterioração da prótese, desgaste da bola e complicações tromboembólicas, o presente trabalho mostrou uma complicação pouco frequente que foi o “pannus” com poucos relatos na literatura. A cirurgia de troca valvar se mostrou tecnicamente simples com exposição cirúrgica facilitada pela dilatação da aorta ascendente, sendo o procedimento de fácil realização e reprodutível.

P - 10 Cirurgia de Troca Válvula de Gaiola após Três Décadas André Luiz Mendes Martins Cardioclínica Paulista Introdução: Em 1960 que STARR & EDWARDS substituíram pela primeira vez uma valva mitral por uma prótese de bola, obtendo bons resultados no longo prazo. A válvula Starr-Edwards de gaiola marcou uma nova era no tratamento de doença cardíaca valvar. As complicações mais comuns relatadas, em relação a esta válvula, são trombose, eventos tromboembolicos, vazamento paravalvar, e formação de panus e ocorrendo em frequências variáveis. Mais de 200.000 proteses foram implantadas em todo o mundo e os resultados se mostraram satisfatórios. A quase totalidade das próteses implantadas já foram substituídas.

P - 11 Coarctação da aorta no adulto: correção cirúrgica do aneurisma de subclávia esquerda em associação com coarctação de aorta e hipoplasia do arco Autor: Wagner Tadeu Jurevicius do Nascimento Incor – HCFMUSP - Residente de Cirurgia Cardiovascular Introdução: A coarctação de aorta (CoAo) consiste em um estreitamento congênito no início da aorta descendente,

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sendo diagnosticado frequentemente por ser uma causa de hipertensão secundária principalmente na segunda ou terceira década de vida. Um estreitamento do istmo da aorta comumente aparece em associação com a coarctação, assim como alterações na parede dos vasos que levam a formação de aneurismas. Apresentamos a correção da coarctação de aorta associado a aneurisma de artéria subclávia esquerda (AASE) diagnosticados na idade adulta. Caso Clínico: Paciente de 21 anos com quadro de dor atípica esporádica desde os 9 anos de vida, principalmente em região superior de hemitórax esquerdo. Apresentava hipertensão arterial sendo considerada a hipótese de coarctação de aorta, confirmada posteriormente por ecocardiografia. Realizada Angiotomografia de aorta torácica que evidenciou estreitamento segmentar da aorta com início após a emergência do tronco braquiocefálico e término após a emergência da artéria subclávia esquerda que era dilatada. Procedimento cirúrgico e evolução: A abordagem foi por esternotomia mediana com incisão prolongada para região clavicular esquerda. Na cirurgia foi identificado arco hipoplásico, artéria subclávia aneurismática e logo após sua emergência uma região de coarctação. A correção cirúrgica foi realizada através da interposição de tubo de dacron número 18 na região do estreitamento aórtico e substituída região aneurismática da artéria subclávia por um tubo número 12. Paciente foi extubado no pós operatório imediato em uso de dobutamina e nipride e sem sangramento significativo. Apresentou boa evolução hemodinâmica e neurológica, com alta da UTI no 3oPO. Recebeu alta hospitalar no 8oPO. Discussão: A ocorrência de aneurisma de subclávia em associação com coarctação de aorta e hipoplasia do arco aórtico é descrito na literatura. Sendo outras alterações vasculares presentes em 59 a 92% e a hipoplasia do arco em 33% dos casos2. A presença de AASE pode evoluir com rotura, sendo que sua associação à coarctação da aorta pode levar ao óbito caso não diagnosticado precocemente. A correção completa permite reestabelecimento do fluxo na aorta descendente e substituição da área de aneurisma sob risco de rotura.

para a realização de biopsias endomiocárdicas em situações especiais onde condução do paciente até a sala de hemodinâmica é acompanhada de alto risco ou a fluoroscopia está contraindicada. Objetivo: Análise da experiência acumulada com a realização da biopsia endomiocárdica em um único centro. Casuística e Método: No período de 1985 a 2010, 72 pacientes foram submetidos a 86 biopsias endomiocárdicas guiadas pela ecocardiografia bidimensional à beira leito, exceto nos 10 (12,1%) primeiros procedimentos onde se empregou simultaneamente a fluoroscopia para validação do método. Nos demais ficou assim distribuído: em 46 (63,9%) pacientes para controle de rejeição, onde foram realizadas 60 (83,3%) biopsias; 10 (13,9%) para avaliação pré-transplante, onde se realizou posteriormente o estudo hemodinâmico direito, e em 6 (8,3%) pacientes para diagnóstico de miocardiopatia. Após avaliação ecocardiográfica geral adotou-se a posição em quatro câmaras para orientar a entrada do biotomo no ventrículo direito por meio da imagem ecodensa. A via de eleição foi a veia jugular direita e a injeção endovenosa de soro fisiológico auxiliou na identificação das câmaras cardíacas. Resultados: Em 1 (1,3%) paciente não foi possível a passagem do biotomo para o ventrículo direito e o procedimento foi repetido com sucesso 2 dias após. Como outras complicações pode se observar: dor em 8 (11,1%) casos; dificuldade de punção em 8 (11,1%), por múltiplas manipulações, e hematoma em 3 (4,1%) casos. Não se constatou nas espécimes de miocárdio retirado fragmentos cujo tamanho foi considerado insuficiente, bem como a extração indesejável de tecido da valva tricúspide. Conclusão: A ecocardiografia é um recurso especial na realização de biopsias endomiocárdicas em pacientes críticos e não oferece risco adicional. P - 13 Análise anatomopatológica dos corações com doença de Chagas explantados de portadores submetidos ao Transplante Cardíaco

P - 12 Biopsia endomiocárdica guiada pela ecocardiografia bidimensional

Autores: Vicente Pereira dos Santos Júnior; Bruno Garcia Canizares; Taline Santos da Costa; Dolma Ribeiro de Farias; Tiago Wanderley Diniz Chamel; Maria Júlia de Aro Braz; Alfredo I. Fiorelli; Fabio B. Jatene.

Dolma Ribeiro de Farias; Tiago Wanderley Diniz Chamel Vicente Pereira dos Santos Júnior; Bruno Garcia Canizares; Taline Santos da Costa; Igor Silva Fernandes Machado; Pedro Queiroz Ferreira Tito; Raif Restivo Simão Alfredo I. Fiorelli; Fabio B. Jatene. Instituição: Instituto do Coração da Universidade de São Paulo/Brasil.

Instituição: Instituto do Coração da Universidade de São Paulo/Brasil. INTRODUÇÃO: A Organização Mundial da Saúde informa que a prevalência da Doença de Chagas no Brasil é próxima de 4%. As repercussões histopatológicas da infecção prejudicam a função de bomba do coração, podendo o transplante ser

Introdução: A ecocardiografia é um método alternativo

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Alfredo I. Fiorelli; Fabio B. Jatene.

a única possibilidade terapêutica para aqueles com extensa disfunção cardíaca devido à doença. OBJETIVO: Analisar retrospectivamente os corações explantados nos pacientes com doença de Chagas e submetidos ao transplante cardíaco do ponto de vista anatomopatológico. METODOLOGIA: Realizou-se uma análise retrospectiva dos laudos anatomopatológicos de todos os corações explantados de portadores de doença de chagas que no período de 1985 a 2010, totalizando 106 casos. Foram analisados os seguintes dados como sexo, idade do paciente, peso do órgão, presença de pericardite, hipertrofia, dilatação, fibrose, miocardite, parasitas, infarto, aneurisma, trombose intramural, aterosclerose coronariana, valvopatia e presença de eletrodos de marca-passo. RESULTADOS: Na casuística (71 homens e 35 mulheres), obteve-se média de idade de 42,5±12,8 anos e média do peso dos corações de 405,8±87,6 gramas. Temos que 12,3% dos casos apresentaram pericardite; 68,9% com dilatação biventricular; 22,7% com hipertrofia; 35,9% com algum tipo de fibrose (sendo que 23,6% da amostra tiveram a lesão em ápice de ventrículo esquerdo); 49,1% com miocardite crônica; 9,4% com parasitas; 3,8% com infarto; 13,2% com aneurisma; 28,3% com trombo intramural; 7,54% com aterosclerose coronariana; 50,9% com alteração valvar e 23,6% com marca-passo. CONCLUSÕES: Os dados obtidos no estudo apontam que as alterações anatopatológicas dos corações de pacientes com Doença de Chagas submetidos ao transplante cardíaco não diferem significativamente dos achados de necropsia de outros pacientes chagásicos, diferindo quanto a intensidade e a extensão da doença.

Instituição: Instituto do Coração da Universidade de São Paulo/Brasil. Introdução: A insuficiência tricúspide (IT) é uma complicação frequente após o transplante cardíaco, tendo correlação etiológica multifatorial, como a biópsia endomiocárdica. Objetivo: Avaliar a presença de tecido valvar tricúspide nos fragmentos obtidos nas biópsias endomiocárdicas, de rotina, realizadas para o controle de episódios de rejeição após o transplante cardíaco. Casuística e Método: Foram estudados dois grupos distintos de pacientes submetidos ao transplante cardíaco (coorte); Grupo 1 – com 23 pacientes operados entre 1985 e 1986, e o Grupo 2 – com 134 pacientes operados entre 2000 e 2009. Os pacientes foram assim divididos, pois na primeira fase da experiencia não se usava a cintilografia com gálio-67 no controle da rejeição. Todas as lâminas foram revisadas por dois observadores diferentes. Resultados: No Grupo 1 foram contabilizadas 644 biópsias (28/paciente), sendo encontrados fragmentos de valva tricúspide (quatro fragmentos), em 0,62% das biópsias. No Grupo 2 constituído por 584 biópsias (4,4/paciente) em 0,86% das biópsias houve presença de valva (cinco fragmentos). No primeiro grupo o número de biópsias realizadas foi cerca de 7 vezes maior (p=0,01), todavia, o risco de lesão valvar se mostrou similar e muito baixo em ambos os grupos (p=0,3), a despeito da introdução da cintilografia na prática clínica rotineira, não sendo significativo a relação entre a presença valvar e o número de biópsias realizadas por cada paciente em cada um dos dois grupos, nem entre os dois grupos (p=0,12). Conclusões: A biopsia endomiocárdica, ainda considerada como método padrão no controle e diagnóstico dos episódios de rejeição, é realizada com baixo risco, não determinando maior risco de insuficiência tricúspide, secundária a lesão traumática valvar, na evolução do paciente submetido a transplante cardíaco. A despeito disso, a adoção do mapeamento com o gálio-67 motivou a redução do número de biopsias.

P - 14 Biópsia endomiocárdica e a lesão traumática da valva tricúspide Leonardo Ervolino Corbi; Gabriel Erra Ramos; Igor Silva Fernandes Machado; Pedro Queiroz Ferreira Tito; Raif Restivo Simão; Rômulo dos Santos Sobreira Nunes;

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REVIEWERS

Reviewers BJCVS/RBCCV 28.4 Below, the names of the reviewers who evaluated the articles published in this issue of the Brazilian Journal of Cardiovascular Surgery / Revista Brasileira de Cirurgia Cardiovascular (BJCVS/RBCCV). To them, my thanks for their dilettante work, essential to maintain and enhance the scientific level of our journal.

Domingo Braile Editor-In-Chief BJCVS

Adriana Soares Alexandre Hueb Alexandre Visconti Brick Alfredo Inácio Fiorelli Ana Maria Rocha Pinto e Silva Ana Paula Marques Lima-Oliveira

Lindemberg da Mota Silveira Filho Luciano Albuquerque Luís Alberto Oliveira Dallan Marcos Aurélio Barboza de Oliveira Marcus Vinicius Ferraz de Arruda Marcos Vinícius Pinto e Silva Maria Cristina de Oliveira Santos Miyazaki Mauro Paes Leme de Sá

Bruno Botelho Pinheiro Bruno da Costa Rocha

Neide Aparecida Micelli Domingos

Carla Tanamati Claudia Bernardi Cesarino

Orlando Petrucci

Diego Felipe Gaia

Paulo Roberto Barbosa Evora

Edmo Atique Gabriel Ektor Correa Vrandecic Enio Buffolo

Reinaldo Wilson Vieira Stevan Krieger Martins

Fausto Miranda Junior

Tomas Salerno

Gilberto Venossi Barbosa

Valdester Cavalcanti Pinto Junior Valquíria Pelisser Campagnucci Vera Demarchi Aiello

João de Deus e Brito José Honório Palma Juliana Bassalobre Carvalho Borges

Walter Gomes

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SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY E-mail: revista@sbccv.org.br Sites: www.scielo.br/rbccv www.rbccv.org.br

RBCCV em números 27 anos de circulação ininterrupta Fator de Impacto 0,809

www.rbccv.org.br www.scielo.br/rbccv www.bjcvs.org

Consultada por leitores de mais de 110 países 788.564 acessos no site próprio (www.rbccv.org.br) em 2012 709.180 acessos no site da SciELO (www.scielo.br/rbccv) em 2012 4092 visitantes diariamente 469,65 gigabytes (GB) transferidos, média de 1,28 GB por dia 47.232.073 impressões de páginas em 2012 (requisição do navegador de um visitante para uma página web que possa ser exibida), média diária de 129.049,38. Presente em nas bases de dados EBSCO, Lilacs, Scielo, Latindex, Index Copernicus, Scopus, PubMed, Thomson Scientific (ISI), Google Scholar

Fig.1 – Número de acessos ao site da RBCCV em 2012

Fig. 2 – Transferência de bytes no site da RBCCV durante 2012

Fig. 3 – Número de impressões de páginas da RBCCV em 2012