· auis bsileis de cdili - volume 102, 6, une 2014 a journal of sociedade brasileira de...

www.arquivosonline.com.br Sociedade Brasileira de Cardiologia • ISSN-0066-782X • Volume 102, Nº 6, June 2014

EditorialEpicardial Ablation for Ventricular Tachycardia in Chronic Chagas

Heart Disease

Original ArticlesLong-term Outcomes of Drug-eluting versus Bare-metal Stent for ST-

elevation Myocardial Infarction

Applicability of Two International Risk Scores in Cardiac Surgery in a

Reference Center in Brazil

Infarct Size as Predictor of Systolic Functional Recovery after

Myocardial Infarction

Mortality by Heart Failure and Ischemic Heart Disease in Brazil from

1996 to 2011

Femoral versus Radial Access in Primary Angioplasty. Analysis of the

ACCEPT Registry

Blood Pressure Control in Hypertensive Patients in the “Hiperdia

Program”: A Territory-Based Study

Baroreflex Sensitivity and its Aassociation with Arrhythmic events in

Chagas Disease

Tai Chi Chuan for Cardiac Rehabilitation in Patients with Coronary

Arterial Disease

Teaching Basic Life Support to Students of Public and Private

High Schools

Review ArticleClinical and Echocardiographic Predictors of Mortality in Chagasic

Cardiomyopathy - Systematic Review

Letter to the EditorAngiotensin-converting enzyme genetic polymorphism

Assessment of Diastolic Dysfunction: Drugs Could alter the Results

Eletronic Pages

Clinicoradiological SessionCase 4 / 2014 – 15-year-old Patient with Atrial Septal Aneurysm,

Right Bundle Branch Block and Paroxysmal Atrial Fibrillation

Case ReportShort-Coupled Variant of “Torsades de Pointes” and Polymorphic

Ventricular Tachycardia

ViewpointCardiohepatic Interactions – from Humoral Theory to Organ

Transplantation

Figure 2 – Technique of access to the normal pericardial space. A: Subxiphoid puncture with Tuhoy needle. The epigastric compression makes it easier to introduce the needle in the pericardial space, lowering the risk of intra-abdominal organ perforation, mainly the liver. B: Heart fluoroscopy in left anterior oblique projection (LAO) showing the right positioning of the guide wire in the pericardial space. C, D, E: Fluoroscopic aspects in right anterior oblique (RAO) and LAO of the positioning of the exploratory catheter on the heart epicardial surface. Page: 526

Arquivos Brasileiros de Cardiologia - Volume 102, Nº 6, June 2014

A JOURNAL OF SOCIEDADE BRASILEIRA DE CARDIOLOGIA - Published since 1948

Contents

Editorial

Epicardial Ablation for Ventricular Tachycardia in Chronic Chagas Heart DiseaseMauricio Scanavacca.....................................................................................................................................................................page 524

Original Articles

Coronary Angioplasty with and without Stent

Long-term Outcomes of Drug-eluting versus Bare-metal Stent for ST-elevation Myocardial InfarctionLiping Wang, Hongyun Wang, Pingshuan Dong, Zhuanzhen Li, Yanyu Wang, Nana Duan, Yuwei Zhao, Shaoxin Wang.....................................................................................................................................................................page 529

Heart Surgery - Adults

Applicability of Two International Risk Scores in Cardiac Surgery in a Reference Center in BrazilSilvia Bueno Garofallo, Daniel Pinheiro Machado, Clarissa Garcia Rodrigues, Odemir Bordim Jr., Renato A. K. Kalil, Vera Lúcia Portal.....................................................................................................................................................................page 539

Chronic Coronary Artery Disease

Infarct Size as Predictor of Systolic Functional Recovery after Myocardial InfarctionMarcos F. Minicucci, Elaine Farah, Daniéliso R. Fusco, Ana Lúcia Cogni, Paula S. Azevedo, Katashi Okoshi, Silméia G. Zanati, Beatriz B. Matsubara, Sergio A. R. Paiva, Leonardo A. M. Zornoff.....................................................................................................................................................................page 549

Epidemiology

Mortality by Heart Failure and Ischemic Heart Disease in Brazil from 1996 to 2011Eduardo Nagib Gaui, Gláucia Maria Moraes de Oliveira, Carlos Henrique Klein.....................................................................................................................................................................page 557

Hemodynamics - Adults

Femoral versus Radial Access in Primary Angioplasty. Analysis of the ACCEPT RegistryPedro Beraldo de Andrade, Mônica Vieira Athanazio de Andrade, Robson Alves Barbosa, André Labrunie, Mauro Esteves Hernandes, Roberto Luiz Marino, Dalton Bertolim Precoma, Francisco Carleial Feijó de Sá, Otávio Berwanger, Luiz Alberto Piva e Mattos.....................................................................................................................................................................page 566

Hypertension

Blood Pressure Control in Hypertensive Patients in the “Hiperdia Program”: A Territory-Based StudyClarita Silva de Souza, Airton Tetelbom Stein, Gisele Alsina Nader Bastos, Lucia Campos Pellanda.....................................................................................................................................................................page 571


Other Diagnostic Tests (not involving imaging)

Baroreflex Sensitivity and its Aassociation with Arrhythmic events in Chagas DiseaseAstrid Meireles Santos, Mauricio Ibrahim Scanavacca, Francisco Darrieux, Bárbara Ianni, Sissy Lara de Melo, Cristiano Pisani, Francisco Santos Neto, Eduardo Sosa, Denise Tessariol Hachul.....................................................................................................................................................................page 579

Cardiovascular Rehabilitation

Tai Chi Chuan for Cardiac Rehabilitation in Patients with Coronary Arterial DiseaseRosane Maria Nery, Maurice Zanini, Juliana Nery Ferrari, César Augusto Silva, Leonardo Fontanive Farias, João Carlos Comel, Karlyse Claudino Belli, Anderson Donelli da Silveira, Antonio Cardoso Santos, Ricardo Stein.....................................................................................................................................................................page 588

Intensive Cardiac Care / Emergency Situations

Teaching Basic Life Support to Students of Public and Private High SchoolsJosé Maria Gonçalves Fernandes, Amanda Lira dos Santos Leite, Bruna de Sá Duarte Auto, José Elson Gama de Lima, Ivan Romero Rivera, Maria Alayde Mendonça.....................................................................................................................................................................page 593

Review Article

Clinical and Echocardiographic Predictors of Mortality in Chagasic Cardiomyopathy - Systematic ReviewClodoval de Barros Pereira Júnior and Brivaldo Markman Filho.....................................................................................................................................................................page 602

Letter to the Editor

Angiotensin-converting enzyme genetic polymorphismSomsri Wiwanitkit and Viroj Wiwanitkit.....................................................................................................................................................................page 611

Assessment of Diastolic Dysfunction: Drugs Could alter the ResultsEmre Yalcinkaya, Murat Celik, Baris Bugan.....................................................................................................................................................................page 613


Arquivos Brasileiros de Cardiologia - Eletronic Pages

Clinicoradiological Session

Case 4 / 2014 – 15-year-old Patient with Atrial Septal Aneurysm, Right Bundle Branch Block and Paroxysmal Atrial FibrillationEdmar Atik..................................................................................................................................................................page e57

Case Report

Short-Coupled Variant of “Torsades de Pointes” and Polymorphic Ventricular TachycardiaMuhieddine Omar Chokr, Francisco Carlos da Costa Darrieux, Carina Abigail Hardy, Denise Tessariol Hachul, Allisson Valadão de Oliveira Britto, Sissy Lara de Melo, Cristiano Pisani, Eduardo Argentino Sosa, Martino Martinelli Filho, Mauricio Ibrahim Scanavacca..................................................................................................................................................................page e60

Viewpoint

Cardiohepatic Interactions – from Humoral Theory to Organ TransplantationOdilson Marcos Silvestre, Fernando Bacal, Rafael Oliveira Ximenes, Flair José Carrilho, Luiz Augusto Carneiro D’Albuquerque, Alberto Queiroz Farias..................................................................................................................................................................page e65

* Indicate manuscripts only in the electronic version. To view them, visit: http://www.arquivosonline.com.br/2014/10206/edicaoatual.asp

Editorial BoardBrazilAguinaldo Figueiredo de Freitas Junior (GO)Alfredo José Mansur (SP)Aloir Queiroz de Araújo Sobrinho (ES)Amanda G. M. R. Sousa (SP)Ana Clara Tude Rodrigues (SP)André Labrunie (PR)Andrei Sposito (SP)Angelo A. V. de Paola (SP)Antonio Augusto Barbosa Lopes (SP) Antonio Carlos C. Carvalho (SP) Antônio Carlos Palandri Chagas (SP) Antonio Carlos Pereira Barretto (SP) Antonio Cláudio L. Nóbrega (RJ) Antonio de Padua Mansur (SP)Ari Timerman (SP)Armenio Costa Guimarães (BA)Ayrton Pires Brandão (RJ)Beatriz Matsubara (SP)Brivaldo Markman Filho (PE)Bruno Caramelli (SP)Carisi A. Polanczyk (RS)Carlos Eduardo Rochitte (SP)Carlos Eduardo Suaide Silva (SP) Carlos Vicente Serrano Júnior (SP) Celso Amodeo (SP)Charles Mady (SP)Claudio Gil Soares de Araujo (RJ) Cláudio Tinoco Mesquita (RJ)Cleonice Carvalho C. Mota (MG)Clerio Francisco de Azevedo Filho (RJ)Dalton Bertolim Précoma (PR)Dário C. Sobral Filho (PE)Décio Mion Junior (SP)Denilson Campos de Albuquerque (RJ) Djair Brindeiro Filho (PE)Domingo M. Braile (SP)Edmar Atik (SP)Emilio Hideyuki Moriguchi (RS)

Enio Buffolo (SP)Eulógio E. Martinez Filho (SP) Evandro Tinoco Mesquita (RJ) Expedito E. Ribeiro da Silva (SP)Fábio Vilas-Boas (BA)Fernando Bacal (SP)Flávio D. Fuchs (RS) Francisco Antonio Helfenstein Fonseca (SP)Gilson Soares Feitosa (BA)Glaucia Maria M. de Oliveira (RJ)Hans Fernando R. Dohmann (RJ)Humberto Villacorta Junior (RJ)Ines Lessa (BA)Iran Castro (RS)Jarbas Jakson Dinkhuysen (SP)João Pimenta (SP)Jorge Ilha Guimarães (RS)José Antonio Franchini Ramires (SP)José Augusto Soares Barreto Filho (SE)José Carlos Nicolau (SP)José Lázaro de Andrade (SP)José Péricles Esteves (BA)Leonardo A. M. Zornoff (SP)Leopoldo Soares Piegas (SP)Lucia Campos Pellanda (RS)Luis Eduardo Rohde (RS)Luis Cláudio Lemos Correia (BA)Luiz A. Machado César (SP)Luiz Alberto Piva e Mattos (SP)Marcia Melo Barbosa (MG)Maria da Consolação Moreira (MG)Mario S. S. de Azeredo Coutinho (SC)Mauricio I. Scanavacca (SP)Max Grinberg (SP)Michel Batlouni (SP)Murilo Foppa (RS)Nadine O. Clausell (RS)Orlando Campos Filho (SP)Otávio Rizzi Coelho (SP)

Otoni Moreira Gomes (MG)Paulo Andrade Lotufo (SP)Paulo Cesar B. V. Jardim (GO)Paulo J. F. Tucci (SP)Paulo R. A. Caramori (RS)Paulo Roberto B. Évora (SP)Paulo Roberto S. Brofman (PR)Pedro A. Lemos (SP)Protásio Lemos da Luz (SP)Reinaldo B. Bestetti (SP)Renato A. K. Kalil (RS)Ricardo Stein (RS)Salvador Rassi (GO)Sandra da Silva Mattos (PE)Sandra Fuchs (RS)Sergio Timerman (SP)Silvio Henrique Barberato (PR)Tales de Carvalho (SC)Vera D. Aiello (SP)Walter José Gomes (SP)Weimar K. S. B. de Souza (GO)William Azem Chalela (SP)Wilson Mathias Junior (SP)

Exterior.+Adelino F. Leite-Moreira (Portugal)Alan Maisel (Estados Unidos)Aldo P. Maggioni (Itália)Cândida Fonseca (Portugal)Fausto Pinto (Portugal)Hugo Grancelli (Argentina)James de Lemos (Estados Unidos) João A. Lima (Estados Unidos)John G. F. Cleland (Inglaterra)Maria Pilar Tornos (Espanha)Pedro Brugada (Bélgica)Peter A. McCullough (Estados Unidos)Peter Libby (Estados Unidos)Piero Anversa (Itália)

Scientific Director Maria da Consolação Vieira Moreira

Chief Editor Luiz Felipe P. Moreira

Associated Editors

Clinical Cardiology José Augusto Barreto-Filho

Surgical Cardiology Paulo Roberto B. Evora

Interventionist Cardiology Pedro A. Lemos

Pediatric/Congenital Cardiology Antonio Augusto Lopes

Arrhythmias/Pacemaker Mauricio Scanavacca

Non-Invasive Diagnostic Methods Carlos E. Rochitte

Basic or Experimental Research Leonardo A. M. Zornoff

Epidemiology/Statistics Lucia Campos Pellanda

Arterial Hypertension Paulo Cesar B. V. Jardim

Ergometrics, Exercise and Cardiac Rehabilitation Ricardo Stein

First Editor (1948-1953) † Jairo Ramos

A JOURNAL OF SOCIEDADE BRASILEIRA DE CARDIOLOGIA - Published since 1948www.arquivosonline.com.br

PresidentAngelo Amato V. de Paola

Vice-PresidentSergio Tavares Montenegro

Financial DirectorJacob Atié

Scientific DirectorMaria da Consolação Vieira Moreira

Administrative DirectorEmilio Cesar Zilli

Assistance Quality DirectorPedro Ferreira de Albuquerque

Communication DirectorMauricio Batista Nunes

Information Technology DirectorJosé Carlos Moura Jorge

Government Liaison DirectorLuiz César Nazário Scala

Director of State and Regional AffairsAbrahão Afiune Neto

Cardiovascular Health Promotion Director - SBC/FuncorCarlos Costa Magalhães

Department DirectorEspecializados - Jorge Eduardo Assef

Research DirectorFernanda Marciano Consolim Colombo

Chief Editor of the Brazilian Archives of CardiologyLuiz Felipe P. Moreira

Special Advisor to the PresidencyFábio Sândoli de Brito

Adjunct Coordination

SBC Newsletter EditorNabil Ghorayeb e Fernando Antonio Lucchese

Continuing Education Coordination Estevão Lanna Figueiredo

Norms and Guidelines Coordination Luiz Carlos Bodanese

Governmental Integration Coordination Edna Maria Marques de Oliveira

Regional Integration Coordination José Luis Aziz

Presidents of State and Regional Brazilian Societies of Cardiology

SBC/AL - Carlos Alberto Ramos Macias

SBC/AM - Simão Gonçalves Maduro

SBC/BA - Mario de Seixas Rocha

SBC/CE - Ana Lucia de Sá Leitão Ramos

SBC/CO - Frederico Somaio Neto

SBC/DF - Wagner Pires de Oliveira Junior

SBC/ES - Marcio Augusto Silva

SBC/GO - Thiago de Souza Veiga Jardim

SBC/MA - Nilton Santana de Oliveira

SBC/MG - Odilon Gariglio Alvarenga de Freitas

SBC/MS - Mércule Pedro Paulista Cavalcante

SBC/MT - Julio César De Oliveira

SBC/NNE - Jose Itamar Abreu Costa

SBC/PA - Luiz Alberto Rolla Maneschy

SBC/PB - Catarina Vasconcelos Cavalcanti

SBC/PE - Helman Campos Martins

SBC/PI - João Francisco de Sousa

SBC/PR - Osni Moreira Filho

SBC/RJ - Olga Ferreira de Souza

SBC/RN - Rui Alberto de Faria Filho

SBC/RS - Carisi Anne Polanczyk

SBC/SC - Marcos Venicio Garcia Joaquim

SBC/SE - Fabio Serra Silveira

SBC/SP - Francisco Antonio Helfenstein Fonseca

SBC/TO - Hueverson Junqueira Neves

Sociedade Brasileira de Cardiologia

Presidents of the Specialized Departaments and Study GroupsSBC/DA - José Rocha Faria Neto

SBC/DECAGE - Josmar de Castro Alves

SBC/DCC - José Carlos Nicolau

SBC/DCM - Maria Alayde Mendonça da Silva

SBC/DCC/CP - Isabel Cristina Britto Guimarães

SBC/DIC - Arnaldo Rabischoffsky

SBC/DERC - Nabil Ghorayeb

SBC/DFCVR - Ricardo Adala Benfati

SBC/DHA - Luiz Aparecido Bortolotto

SOBRAC - Luiz Pereira de Magalhães

SBCCV - Marcelo Matos Cascado

SBHCI - Helio Roque Figueira

SBC/DEIC - Dirceu Rodrigues Almeida

GERTC - Clerio Francisco de Azevedo Filho

GAPO - Danielle Menosi Gualandro

GEECG - Joel Alves Pinho Filho

GEECABE - Mario Sergio S. de Azeredo Coutinho

GECETI - Gilson Soares Feitosa Filho

GEMCA - Alvaro Avezum Junior

GECC - Mauricio Wanjgarten

GEPREC - Glaucia Maria Moraes de Oliveira

Grupo de Estudos de Cardiologia Hospitalar - Evandro Tinoco Mesquita

Grupo de Estudos de Cardio-Oncologia - Roberto Kalil Filho

GEEC - Cláudio José Fuganti

GECIP - Gisela Martina Bohns Meyer

GECESP - Ricardo Stein

GECN - Ronaldo de Souza Leão Lima

GERCPM - Artur Haddad Herdy

Arquivos Brasileiros de Cardiologia

Affiliated at the Brazilian Medical Association

Volume 102, Nº 6, June 2014Indexing: ISI (Thomson Scientific), Cumulated Index Medicus (NLM), SCOPUS,

MEDLINE, EMBASE, LILACS, SciELO, PubMed

The ads showed in this issue are of the sole responsibility of advertisers, as well as the concepts expressed in signed articles are of the sole responsibility of their

authors and do not necessarily reflect the views of SBC.

This material is for exclusive distribution to the medical profession. The Brazilian Archives of Cardiology are not responsible for unauthorized access to its contents and

that is not in agreement with the determination in compliance with the Collegiate Board Resolution (DRC) N. 96/08 of the National Sanitary Surveillance Agency

(ANVISA), which updates the technical regulation on Drug Publicity, Advertising, Promotion and Information. According to Article 27 of the insignia, "the advertisement or publicity of prescription drugs should be restricted solely and exclusively to health

professionals qualified to prescribe or dispense such products (...)".

To ensure universal access, the scientific content of the journal is still available for full and free access to all interested parties at:

www.arquivosonline.com.br.

SUPPORT

Commercial Department

Phone: (11) 3411-5500

E-mail: [email protected]

Editorial Production

SBC - Internal Publication Department

Graphic Design and DiagrammingSBC - Internal Design Department

PrintImos

Circulation1.500 copies

Address: Av. Marechal Câmara, 160 - 3º andar - Sala 330 20020-907 • Centro • Rio de Janeiro, RJ • Brasil

Phone.: (21) 3478-2700

E-mail: [email protected]

www.arquivosonline.com.br

SciELO: www.scielo.br

Editorial

Epicardial Ablation for Ventricular Tachycardia in Chronic Chagas Heart DiseaseMauricio ScanavaccaInstituto do Coração (InCor) -HC-FMUSP. Sáo Paulo, SP - Brazil

Mailing address: Mauricio Scanavacca •Av. Joaquim C. A. Marques, 1.205. Postal Code 05688-021, Morumbi, SP - BrazilEmail: [email protected]

KeywordsChagas Cardiomyopathy; Tachycardia, ventricular;

Catheter ablation.

DOI: 10.5935/abc.20140082

The Chagas Heart Disease, described for the first time in 1909 by Carlos Chagas, is caused by Trypanosoma cruzi, a flagellated protozoa transmitted to humans, mostly by the feces of Triatoma infestans in endemic areas. Estimates are that fifteen million people are infected in Latin America, leading to 45,000 deaths per year, 90% owing to heart disease.

The cardiac involvement is the most prevalent and severe manifestation of Chagas Heart Disease. After the infection, most individuals remain without manifestation of the disease along their lives, but at least 30% develop heart rhythm disorders, severe symptoms of heart failure and thromboembolic events, typically after 10-30 years after infection. Chronic myocarditis predisposes to cardiac dilation and to the formation of ventricular aneurysms. Thrombi are more prevalent in apical ventricular aneurysm, which is typical of the disease, and the cause for thromboembolic events in the systemic and pulmonary circulation. Segmental myocardial fibrosis is the anatomical substrate for ventricular arrhythmias and atrio-ventricular and intraventricular conduction abnormalities. Sudden death occurs in 55-65% of the patients, at times in the absence of prior cardiac symptoms. Death as a result of heart failure happens in 25-30%, and cerebral or pulmonary embolism, in 10-15%1-3.

Ventricular extrasystoles are rather common in patients with Chagas Heart Disease, and its prevalence and complexity are associated with the extent of myocardial injury, particularly with left ventricular dysfunction and dilation4. Non-sustained ventricular tachycardia (NSVT) has been recognized as an independent risk factor for death and included in score for risk stratification5. Sustained ventricular tachycardia (SVT) is considered the main cause of sudden death, and may happen in different stages of the disease and even in patients without important ventricular dysfunction6.

Amiodarona is the most commonly used antiarrhythmic drug in Brazil to treat ventricular arrhythmias in patients with Chagas Heart Disease. Cohort studies involving patients with sustained Chagas Heart Disease and VT revealed 5-11.9% of annual mortality, with sudden death representing 61-78% of the cases, mostly with

important ventricular systolic dysfunction7-10. On account of this, the implantable cardioverter defibrillator (ICD) has been recommended to patients with sustained VT and ventricular dysfunction11-14. However, patients with Chagas Heart Disease seem to receive more ICD shocks compared to patients with coronary heart disease. A relevant finding was the annual mortality of 16.6% in a cohort of 90 patients with Chagas Heart Disease subject to ICD implantation due to sustained VT. Although the patients presented low rate of sudden death, they had a significant rate of total mortality. Patients with more than four shocks over a period of 30 days presented higher mortality compared to patients with no shock or a smaller number11. Since these patients mostly died from heart failure, one can speculate that excessive shocks applied by ICD may depress the ventricular function and increase non-sudden mortality. This data corroborate the indication of catheter ablation as the logical strategy to reduce the recurrence of sustained VT and prevent ICD shocks15.

Catheter Ablation of Sustained VT in Chagas Heart Disease

The main mechanism of SVT of chronic Chagas Heart Disease is the reentry located in a left ventricle inferolateral and baseline scar in more than 70% of the cases16,17. The reentrant circuit of SVT may involve subendocardial, intramyocardial and subepicardial fibers. In some patients, the reentrant circuits have their genesis in places with very thin walls and, on account of that, conventional pulses of RF, emitted from the endocardium, may cause transmural injury and reach all the structures potentially involved in the circuit. Nevertheless, in others, the segmental injury is intramural and the circuit is predominantly kept by subepicardial fibers. Insofar as the contralateral subendocardial tissue is very thick, it may prevent RF applications from reaching the causative intramyocardial and subepicardial fibers and be the reason for an unsuccessful procedure. This was the initial hypothesis for resorting to the transthoracic subxiphoid percutaneous approach to explore the pericardial space and identify patients with possible subepicardial circuits15.

Epicardial Ablation of Sustained VT in Chagas Heart Disease

The transthoracic epicardial approach has been used since 1995 for mapping and ablation of sustained VT in patients with Chagas Heart Disease18 and subsequently also applied in patients with other heart diseases19. The experience acquired over time confirmed the initial findings20-23, and consensus documents issued by different medical societies report

524

Editorial

ScanavaccaEpicardial Ablation for Ventricular Tachycardia in Chronic Chagas Heart Disease

Arq Bras Cardiol. 2014; 102(6):524-528

Figure 1 – Access to the normal pericardial space for epicardial mapping and ablation by subxiphoid puncture. In detail, the Tuhoy needle drawn for epidural anesthesia and used in this procedure to mitigate the risk of cardiac perforation.

that it is necessary in at least 20% of the patients subject of SVT ablation in tertiary centers, mainly in patients with non-ischemic heart diseases24,25. Recent review underscores the current importance of the subxiphoid percutaneous approach in several intrapericardial procedures26.

The technique of access to the periocardial space has been kept virtually unchanged over time, with nearly no technological advance for its performance27. The Tuohy needle is the main tool to reach the pericardial space (Figure 1). It is curved at one end, which makes it easier to penetrate pericardial membranes (Figure 2). A risk of 10% of pericardial bleeding is forecasted when applying this technique, usually a minor and transient one. The risk of severe bleeding demanding surgical repair is around 1-2%. In most patients subject to this approach, the epicardial mapping widens the exploration area. Pericardial adhesions are not common after prior ablations either.

The electrophysiological signs obtained during the epicardial mapping show patterns similar to those obtained with the endocardial mapping, whether in patients with Chagas Heart Disease or with other heart diseases. Delayed potentials are most predominantly found in the target area during mapping in sinus rhythm and pre-systolic activity. Meso-diastolic and continuous activities are also frequent in the original place of VT. The critical isthmus of the reentrant circuit in the subepicardial tissue may be confirmed by entrainment maneuvers or interruption of VT during the application of RF in these places, as can be observed by the endocardial approach. The prevalence of epicardial VT in 257 consecutive patients was higher in patients with Chagas Heart Disease (37%) compared

to patients after myocardial infarction (28%) and patients with idiopathic dilated cardiomyopathy (24%)28.

Three anatomical aspects of the epicardial surface may hamper the efficiency of epicardial ablation: the presence of epicardial coronary artery, a thick layer of fat and the risk of causing injury in neighboring tissues, such as the phrenic nerve29. For all these reasons and more, a substantial number of patients still present clinical recurrences after endocardial and epicardial ablation, whether due to limitations found during the procedure or to the evolution of the disease. The recurrence rate seems to decrease after the introduction of electroanatomic mapping to establish the scar extension and limits (Figures 3 and 4), and irrigated-tip catheter ablations (deeper injuries, even in the presence of fat) may bring on wider substrate injuries30. Alternatively, wider epicardial injuries may increase the risk of damaging the coronary arteries and extracardiac structures31,32.

Prospective randomized study is required to evaluate the role and risks of different strategies during catheter ablations in patients with Chagas Heart Disease33-38. However, there is a special group of patients to whom catheter ablation presents arguable benefits: patients with ICD receiving multiple shocks, regardless of the adjuvant therapy with antiarrhythmic drugs. In these cases, the clinical outcomes are very clear in short and medium-term evaluations39. It is worth noting that the Chagas Heart Disease has a progressive nature, and it is not uncommon for patients with good left ventricular function to have favorable SVT ablations, but return 5-10 years afterwards presenting left ventricular dysfunction and recurrence of new SVT.

525

Editorial


Arq Bras Cardiol. 2014; 102(6):524-528

Figure 2 – Technique of access to the normal pericardial space. A: Subxiphoid puncture with Tuhoy needle. The epigastric compression makes it easier to introduce the needle in the pericardial space, lowering the risk of intra-abdominal organ perforation, mainly the liver. B: Heart fluoroscopy in left anterior oblique projection (LAO) showing the right positioning of the guide wire in the pericardial space. C, D, E: Fluoroscopic aspects in right anterior oblique (RAO) and LAO of the positioning of the exploratory catheter on the heart epicardial surface.

Figure 3 – Electroanatomic mapping in patients with Sustained Ventricular Tachycardia (SVT) secondary to Chronic Chagas’ Cardiomyopathy (CCC). A: ECG in sinus rhythm. Note that there are no disturbances of the atrioventricular and intraventricular conduction or electrically inactive areas, but only change of repolarization of the left ventricle (LV) inferior and lateral walls, secondary to the segmental scar located in the same regions (panels C and D). B: ECG of SVT with electrocardiographic pattern suggesting origin in the LV baseline region (positive QRS of V1 to V6), with onset of ventricular activation on the lateral wall (negative QRS in DI and aVL and positive in D2, D3 and aVF). C: 3D electroanatomic mapping of the LV endocardial and epicardial surfaces in sinus rhythm with the Carto system. The colors represent the amplitude of the ventricular electrograms in the investigated regions. Note that the low-voltage area, suggesting the presence of scar, is predominantly epicardial. D: Integration of the endocardium and epicardium maps showing the LV inferior lateral and baseline segmental injury, anatomical substrate for SVT in this patient.

526

Editorial


Arq Bras Cardiol. 2014; 102(6):524-528

1. Andrade JP, Marin-Neto JA, Paola AA, et al. I Latin American guidelines for the diagnosis and treatment of Chagas cardiomyopathy. Arq Bras Cardiol. 2011;97(2 Suppl 3):1-48

2. Pinto Dias JC. Natural history of Chagas disease. Arq Bras Cardiol. 1995;65(4):359-66.

3. Rassi Jr A, Rassi A, Marin-Neto JA. Chagas disease. Lancet 2010; 375: 1388–402.

4. Barretto AC, Mady C, Ianni BM, Arteaga E, Cardoso RH, da Luz PL, Pileggi F. Relationship between ventricular arrhythmia and cardiac function in Chagas disease. Arq Bras Cardiol. 1995;64(6):533-5.

5. Rassi A Jr, Rassi A, Little WC, et al. Development and validation of a risk score for predicting death in Chagas’ heart disease. N Engl J Med 2006;355: 799–808.

6. Sternick EB, Martinelli M, Sampaio R, Gerken LM, Teixeira RA, Scarpelli R, Scanavacca M, Nishioka SD, Sosa E. Sudden cardiac death in patients with Chagas heart disease and preserved left ventricular function. J Cardiovasc Electrophysiol. 2006;17(1):113-6.

7. Scanavacca MI, Sosa EA, Lee JH, et al. Empiric therapy with amiodarona in patients with chronic Chagas cardiomyopathy and sustained ventricular tachycardia. Arq Bras Cardiol 1990;54(6):367-71.

8. Leite LR, Fenelon G, Simões JR, et al. Clinical usefulness of electrophysiology testing in patients with ventricular tachycardia and chronic chagasic cardiomyopathy treated with amiodarona or sotalol. J Cardiovasc Electrophysiol 2003;14:567–73.

9. Sarabanda AV, Marin-Neto JA. Predictors of mortality in patients with Chagas’ cardiomyopathy and ventricular tachycardia not treated with implantable cardioverter-defibrillators. Pace 2011; 34(1):54-62.

10. Rassi A Jr. Implantable cardioverter-defibrillators in patients with Chagas heart disease: misperceptions, many questions and the urgent need for a randomized clinical trial. J Cardiovasc Electrophysiol 2007; 18(12):1241–3.

11. Cardinalli-Neto A, Bestetti RB, Cordeiro JA, et al. Predictors of all-cause mortality for patients with chronic Chagas’ heart disease receiving implantable cardioverter defibrillator therapy. J Cardiovasc Electrophysiol 2007;18(12):1236–40.

12. Martinelli M, de Siqueira SF, Sternick EB, Rassi A Jr, Costa R, Ramires JA, Kalil Filho R. Long-term follow-up of implantable cardioverter-defibrillator for secondary prevention in chagas’ heart disease Am J Cardiol. 2012 ;110(7):1040-5.

13. Barbosa MP, Rocha MO, Lombardi F, Ribeiro AL. ICDs in Chagas heart disease: the standard treatment for secondary prevention of sudden deathEuropace. 2013;15(9):1383-4.

14. Gali WL, Sarabanda AV, Baggio JM, Ferreira LG, Gomes GG, Marin-Neto JA, Junqueira LF.Implantable cardioverter-defibrillators for treatment of sustained ventricular arrhythmias in patients with Chagas’ heart disease: comparison with a control group treated with amiodarone alone. Europace. 2014;16(5):674-80.

15. Scanavacca MI, de Brito FS, Maia I, et al. Brasileira de Cardiologia S. Guidelines for the evaluation and treatment of patients with cardiac arrhythmias. Arq Bras Cardiol 2002;79(Suppl 5):1–50.

References

Figure 4 – SVT ablation in the same patient of Figure 3. A: Electrophysiological scan documenting the moment of application of RF pulse by epicardial catheter with interrupts SVT and restores the sinus rhythm. I, II, III, V1 and V6: ECG leads synchronized with intracavitary electrograms. RV p and RV d: bipolar electrograms obtained by proximal and distal electrode placements of the right ventricle, respectively. LV epi p and LV epi d: bipolar electrograms obtained, respectively, by proximal and distal electrodes of the epicardial catheter positioned on the LV inferior and lateral scar. VE endo p: bipolar sign of the catheter introduced in the LV. RF: moment of application of radio frequency power, which interrupts SVT. The application is kept by 60 seconds. Speed of registration: 25 mm/s. B: Posterior view of the voltage electroanatomic map showing the limits of LV inferior, lateral and baseline scar. The purple and pink spots indicate places with fractionated and delayed electrograms during the sinus rhythm. The green spots indicate the transition between the left ventricle and left atrium. C: Same electroanatomic mapping view showing the RF applications (red spots) in the SVT origin site.

LV

LV

LV

RV

RV

527

Editorial


Arq Bras Cardiol. 2014; 102(6):524-528

16. Sarabanda AV, Sosa E, Simões MV, et al. Ventricular tachycardia in Chagas’ disease: a comparison of clinical, angiographic, electrophysiologic and myocardial perfusion disturbances between patients presenting with either sustained or nonsustained forms. Int J Cardiol 2005;102(1):9–19.

17. de Mello RP, Szarf G, Schvartzman PR, Nakano EM, Espinosa MM, Szejnfeld D, Fernandes V, Lima JA, Cirenza C, De Paola AA. Delayed enhancement cardiac magnetic resonance imaging can identify the risk for ventricular tachycardia in chronic Chagas’ heart disease. Arq Bras Cardiol. 2012;98(5):421-30.

18. Sosa E, Scanavacca M, d’Avila A, et al. A new technique to perform epicardial mapping in the electrophysiology laboratory. J Cardiovasc Electrophysiol 1996;7(6):531–6.

19. Sosa E, Scanavacca M, D’Avila A, et al. Radiofrequency catheter ablation of ventricular tachycardia guided by nonsurgical epicardial mapping in chronic chagasic heart disease. Pacing Clin Electrophysiol 1999;22:128–30.

20. Sosa E, Scanavacca M, d’Avila A, Oliveira F, Ramires JA. Nonsurgical transthoracic epicardial catheter ablation to treat recurrent ventricular tachycardia occurring late after myocardial infarction. J Am Coll Cardiol. 2000;35:1442–1449.

21. Sacher F, Roberts-Thomson K, Maury P, Tedrow U, Nault I, Steven D, Hocini M, Koplan B, Leroux L, Derval N, Seiler J, Wright MJ, Epstein L, Haissaguerre M, Jais P, Stevenson WG. Epicardial ventricular tachycardia ablation a multicenter safety study. J Am Coll Cardiol. 2010;55:2366 –2372.

22. Della Bella P, Brugada J, Zeppenfeld K, Merino J, Neuzil P, Maury P, Maccabelli G, Vergara P, Baratto F, Berruezo A, Wijnmaalen AP. Epicardial ablation for ventricular tachycardia: a European multicenter study. Circ Arrhythm Electrophysiol. 2011;4:653– 659.

23. Fox MC, Lakdawala N, Miller AL, Loscalzo J. Clinical problem-solving. A patient with syncope.N Engl J Med. 2013;369(10):966-72.

24. Natale A, Raviele A, Al-Ahmad A, Alfieri O, Aliot E, Almendral J, Breithardt G, Brugada J, Calkins H, Callans D, Cappato R, Camm JA, Della Bella P, Guiraudon GM, Haïssaguerre M, Hindricks G, Ho SY, Kuck KH, Marchlinski F, Packer DL, Prystowsky EN, Reddy VY, Ruskin JN, Scanavacca M, Shivkumar K, Soejima K, Stevenson WJ, Themistoclakis S, Verma A, Wilber D; Venice Chart members. Venice Chart International Consensus document on ventricular tachycardia/ventricular fibrillation ablation. J Cardiovasc Electrophysiol. 2010;21(3):339-79.

25. Aliot EM, Stevenson WG, Almendral-Garrote JM, Bogun F, Calkins CH, Delacretaz E, Bella PD, Hindricks G, Jais P, Josephson ME, Kautzner J, Kay GN, Kuck KH, Lerman BB, Marchlinski F, Reddy V, Schalij MJ, Schilling R, Soejima K, Wilber D. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Europace. 2009;11:771– 817.

26. Boyle NG, Shivkumar K. Epicardial interventions in electrophysiology. Circulation. 2012;126(14):1752-69.

27. Pisani CF, Lara S, Scanavacca M. Epicardial ablation for cardiac arrhythmias: techniques, indications and results. Curr Opin Cardiol. 2014;29(1):59-67.

28. Scanavacca M, Sosa E. Epicardial Ablation of Ventricular Tachycardia in Chagas Heart Disease. In: Shivkumar K, Boyle NG, eds. Cardiac

Electrophysiology Clinics: Epicardial Interventions in Electrophysiology. Vol 2. Philadelphia, PA: Saunders; 2010:55– 67.

29. D’Avila A, Scanavacca M, Sosa E, Ruskin JN, Reddy VY. Pericardial anatomy for the interventional electrophysiologist. J Cardiovasc Electrophysiol. 2003;14:422– 430.

30. Valdigem BP, da Silva NJ, Dietrich CO, Moreira D, Sasdelli R, Pinto IM, Cirenza C, de Paola AA. Accuracy of epicardial electroanatomic mapping and ablation of sustained ventricular tachycardia merged with heart CT scan in chronic Chagasic cardiomyopathy. J Interv Card Electrophysiol. 2010;29(2):119-25.

31. Viles-Gonzalez JF, de Castro Miranda R, Scanavacca M, Sosa E, d’Avila A. Acute and chronic effects of epicardial radiofrequency applications delivered on epicardial coronary arteries.Circ Arrhythm Electrophysiol. 2011;4:526-31.

32. Koruth JS, Aryana A, Dukkipati SR, Pak HN, Kim YH, Sosa EA, Scanavacca M, Mahapatra S, Ailawadi G, Reddy VY, d’Avila A. Unusual complications of percutaneous epicardial access and epicardial mapping and ablation of cardiac arrhythmias. Circ Arrhythm Electrophysiol. 2011;4: 882–888.

33. Reddy VY, Reynolds MR, Neuzil P, Richardson AW, Taborsky M, Jongnarangsin K, Kralovec S, Sediva L, Ruskin JN, Josephson ME: Prophylactic catheter ablation for the prevention of defibrillator therapy. N Engl J Med 2007;357:2657-2665.

34. Sacher F, Wright M, Derval N, Denis A, Ramoul K, Roten L, Pascale P, Bordachar P, Ritter P, Hocini M, Dos Santos P, Haissaguerre M, Jais P. Endocardial versus epicardial ventricular radiofrequency ablation: utility of in vivo contact force assessment. Circ Arrhythm Electrophysiol. 2013;6(1):144-50.

35. Di Biase L, Santangeli P, Burkhardt DJ, Bai R, Mohanty P, Carbucicchio C, Dello Russo A, Casella M, Mohanty S, Pump A, Hongo R, Beheiry S, Pelargonio G, Santarelli P, Zucchetti M, Horton R, Sanchez JE, Elayi CS, Lakkireddy D, Tondo C, Natale A. Endo-epicardial homogenization of the scar versus limited substrate ablation for the treatment of electrical storms in patients with ischemic cardiomyopathy. J Am Coll Cardiol. 2012;60(2):132-41.

36. Komatsu Y, Sacher F, Cochet H, Jaïs P. Multimodality imaging to improve the safety and efficacy of epicardial ablation of scar-related ventricular tachycardia. J Cardiovasc Electrophysiol. 2013;24(12):1426-7.

37. de Chillou C, Groben L, Magnin-Poull I, Andronache M, MagdiAbbas M, Zhang N, Abdelaal A, Ammar S, Sellal JM, Schwartz J, Brembilla-Perrot B, Aliot E, Marchlinski FE. Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm.Heart Rhythm. 2014;11(2):175-81.

38. Silberbauer J, Oloriz T, Maccabelli G, Tsiachris D, Baratto F, Vergara P, Mizuno H, Bisceglia C, Marzi A, Sora N, Guarracini F, Radinovic A, Cireddu M, Sala S, Gulletta S, Paglino G, Mazzone P, Trevisi N, Della Bella P. Non-Inducibility and Late Potential Abolition: A Novel Combined Prognostic Procedural Endpoint for Catheter Ablation of Post-infarction Ventricular Tachycardia. Circ Arrhythm Electrophysiol. 2014 May 15. pii: CIRCEP.113.001239.

39. Henz BD, do Nascimento TA, Dietrich Cde O, Dalegrave C, Hernandes V, Mesas CE, Leite LR, Cirenza C, Asirvatham SJ, de Paola AA. Simultaneous epicardial and endocardial substrate mapping and radiofrequency catheter ablation as first-line treatment for ventricular tachycardia and frequent ICD shocks in chronic chagasic cardiomyopathy. J Interv Card Electrophysiol. 2009;26(3):195-205

528

Original Article

Long-term Outcomes of Drug-eluting versus Bare-metal stent for ST-elevation Myocardial InfarctionLiping Wang, Hongyun Wang, Pingshuan Dong, Zhuanzhen Li, Yanyu Wang, Nana Duan, Yuwei Zhao, Shaoxin WangDepartment of Cardiology, the First Affiliated Hospital, Henan University of Science and Technology, Luoyang City, China

Mailing Address: Shaoxin Wang •Department of Cardiology, The First Affiliated Hospital, Henan University of Science and Technology - Jinghua Road No.24, Luoyang city 471003, China. Email: [email protected] received November 6, 2013; revised January 20, 2014; accepted February 6, 2014

DOI: 10.5935/abc.20140070

Abstract

Background: Long-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) remain uncertain.

Objective: To investigate long-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI).

Methods: We performed search of MEDLINE, EMBASE, the Cochrane library, and ISI Web of Science (until February 2013) for randomized trials comparing more than 12-month efficacy or safety of DES with BMS in patients with STEMI. Pooled estimate was presented with risk ratio (RR) and its 95% confidence interval (CI) using random-effects model.

Results: Ten trials with 7,592 participants with STEMI were included. The overall results showed that there was no significant difference in the incidence of all-cause death and definite/probable stent thrombosis between DES and BMS at long-term follow-up. Patients receiving DES implantation appeared to have a lower 1-year incidence of recurrent myocardial infarction than those receiving BMS (RR = 0.75, 95% CI 0.56 to 1.00, p= 0.05). Moreover, the risk of target vessel revascularization (TVR) after receiving DES was consistently lowered during long-term observation (all p< 0.01). In subgroup analysis, the use of everolimus-eluting stents (EES) was associated with reduced risk of stent thrombosis in STEMI patients (RR = 0.37, p=0.02).

Conclusions: DES did not increase the risk of stent thrombosis in patients with STEMI compared with BMS. Moreover, the use of DES did lower long-term risk of repeat revascularization and might decrease the occurrence of reinfarction. (Arq Bras Cardiol. 2014; 102(6):529-538)

Keywords: Drug-eluting stents; Bare-metal stents; Acute myocardial infarction; Long-term outcomes; Meta-analysis.

Introduction The use of bare-metal stents (BMS) has showed the benefit

in reducing the risk of reocclusion of the ischemia-related artery and the need for repeat revascularization in ST-segment elevation myocardial infarction (STEMI) as compared with balloon angioplasty1. However, more than 20% subjects with STEMI who received BMS implantation during primary percutaneous coronary intervention suffered from in-stent restenosis2. Currently, drug-eluting stents (DES) are increasingly used for treatment of STEMI and remedy the above drawback of BMS3,4.

However, concerns have arisen regarding a potentially higher risk of stent thrombosis with DES related to the reduced endothelialization and healing5, especially in the setting of

STEMI patients with the higher possible thrombotic coronary lesions6. The long-term follow-up of several pivotal studies showed an increased risk of stent thrombosis associated with DES implantation in STEMI subjects compared with BMS7,8, but this result has not been confirmed by other studies3,9. Current clinical evidence based on registry studies and randomized controlled trials (RCTs) focusing on this issue delivering conflicting results. These inconsistent findings confused interventional cardiologists’ stent selection decisions in these specific subjects. Initial meta-analyses showed the efficacy and safety of DES placement at short-term follow-up in the setting of STEMI10,11, with no safety issues. However, the longer-term treatment effect of stent implantation on these high-risk patients remains uncertain. Therefore, here we performed a meta-analysis on basis of the available data from RCTs to elucidate the long-term clinical outcomes of DES versus BMS in patients with STEMI.

Methods

Eligible criteria A study was included if 1) patients with STEMI were randomly

assigned to DES (everolimus- [EES], zotarolimus-, sirolimu- [SES], or paclitaxe-eluting stent [PES]) versus BMS; 2) the data on

529

Original Article

Wang et al.A meta-analysis of DES for STEMI

Arq Bras Cardiol. 2014; 102(6):529-538

efficacy or safety endpoints was available; 3) follow-up duration was no less than 12 months. We restricted our analyses to the DES approved by the US Food and Drug Administration (FDA). Trials would be excluded if the data on patient or procedural characteristics was not available, and post-hoc analyses of RCTs were also excluded.

Study identificationWe systematically searched MEDLINE, EMBASE, the

Cochrane library, and ISI Web of Science for the eligible trials (until July 2013) using the following terms: everolimus-eluting stent, zotarolimus-eluting stent, drug-eluting stent, sirolimus-eluting stent, paclitaxel-eluting stent, bare-metal stent, uncoated stent, ST-segment elevation myocardial infarction, ST-segment elevation acute coronary syndrome. We checked the reference lists of review articles, meta-analyses, and original studies identified by the electronic searches to find other eligible trials. The search was restricted to English-language literature.

Study enrollment, data collection, and quality assessmentTwo investigators independently assessed trial eligibility

using predefined eligibility criteria. The data, such as participant characteristics, lesion and procedural characteristics, and follow-up duration, were extracted. The information on clinical outcomes (e.g. all-cause death, recurrent myocardial infarction, target vessel revascularization [TVR], or definite/probable stent thrombosis) was also recorded independently. Any disagreements were resolved through consensus. The quality of the trials was assessed according to concealment of treatment allocation; blinding of patients, investigators, or clinical outcome assessors; and the proportion of patients with complete clinical follow-up12. Additionally, a numerical score between 0 and 5 was assigned as a measure of study design and reporting quality based on Jadad scale13.

Statistical analysesThe pooling analyses were performed using Review Manager

5.1 software (Cochrane Collaboration, Copenhagen, Denmark). We pooled treatment effects and calculated risk ratios (RRs) with 95% confidence intervals (CI) for all end points by using random-effects model. Statistical homogeneity was quantified with the I2 statistic with a scale of 0% to 100% (>75% represented very large between-study inconsistency)14. Subgroup analysis was performed to test the potential influence of clinical factors including the type of DES, time from pain to angioplasty, dual antiplatelet therapy duration, and the percentage of use of glycoprotein IIb/IIIa inhibitors. Overall estimates in subgroup analyses were calculated based on the longest observations when a trial reported follow-up findings at different time points. For verification of the robustness of the results, sensitivity analyses were conducted by omitting each trial at a time from analysis and then calculating overall estimates for the remaining studies. Publication bias among the enrolled studies was qualitatively assessed using funnel plot method. The significance level was set at p<0.05. This work was organized as the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)15.

Results Our initial search yielded 2,465 potential literature

citations (Figure 1). Among them, 1,209 were excluded by removing duplicate literatures and through review of title. Abstracts from 1,256 articles were reviewed and an additional 1,181 articles were excluded, leaving 75 for full publication review. Thereafter 60 were excluded (31 non-RCTs; 15 for comparing clinical outcomes of various DES; 2 having no data on clinical characteristics; 12 for follow-up period less than 12 months). Finally, we identified 15 articles reporting 10 studies for analysis3,4,16-28.

A total of 7,592 participants with STEMI in the 10 long-term trials were included (Table 1). Of them, 4,601 were randomly allocated to DES group and 2,991 to BMS group. Among the 10 trials, 9 were two arm trials (six for SES vs. BMS16,18-21,23-26,28; two for PES vs. BMS17,22,27; one for EES vs. BMS3) and the rest one was three arm trial (SES vs. PES vs. BMS)4. Seven trials reported 1-year follow-up clinical outcomes3,4,19,20,22,24,26; 3 reported 2-year data4,17,24; 4 reported 3-year date16,18,25,28; and 3 reported more than 4-year data21,23,27. The majority of participants were male and the mean age ranged from 59 years to 64 years. Total stent length per patient ranged from 19mm to 29mm. Dual antiplatelet therapy duration ranged from 3 months to 12 months, and the percentage of use of glycoprotein IIb/IIIa inhibitors was from 51.75% to 100% in the included studies. Additionally, the level of quality for each article was graded with a score of 3 to 4 according to the Jadad scale (Table 1).

The pooling analyses showed that there were no significant differences in the incidence of all-cause death (1-year follow-up: RR = 0.90, p= 0.45, I2= 0%; 2-year: RR = 0.75, p= 0.16, I2= 0%; 3-year: RR = 0.80, p= 0.27, I2= 0%; >4-year: RR = 0.83, p= 0.28, I2= 0%; Figure 2) and definite/probable stent thrombosis (1-year: RR = 0.79, p= 0.15, I2= 0%; 2-year: RR = 0.91, p= 0.79, I2= 0%; 3-year: RR = 1.25, p= 0.33, I2= 0%; >4-year: RR = 1.00, p= 0.99, I2= 0%; Figure 3) between DES and BMS regardless of follow-up duration in patients with STEMI. Moreover, DES seemed likely to reduce the 1-year occurrence of recurrent myocardial infarction (RR = 0.75, 95% CI 0.56 to 1.00, p= 0.05, I2= 0%; Figure 4). However, the superiority of DES became nonsignificant with the prolongation of observation period (all p > 0.10; Figure 4). Notably, the risk of TVR in STEMI patients receiving DES placement was dramatically lowered compared with that receiving BMS during 1-year to 3-year follow-up (1-year follow-up: RR = 0.47, 95% CI 0.37 to 0.61, p< 0.001, I2= 30%; 2-year: RR = 0.42, 95% CI 0.25 to 0.70, p< 0.001, I2= 37%; 3-year: RR = 0.53, 95% CI 0.39 to 0.72, p< 0.001, I2= 0%), and the favorable effect of DES remained almost constant up to the maximum observed follow-up of more than 4 years (RR = 0.57, 95% CI 0.42 to 0.76, p< 0.001, I2= 0%; Figure 5).

In subgroup analyses, the second-generation DES, EES, might provide a benefit in lowering the risk of stent thrombosis in STEMI patients (RR = 0.37, 95% CI 0.15 to 0.87, p=0.02, Table 2), whereas both the first-generation SES and PES did not show the benefit compared with BMS (both p > 0.1, Table 2). Except for this, there were no significant influences of several important clinical factors, such as the type of DES, time from symptom to angioplasty, dual antiplatelet therapy duration,

530

Original Article


Arq Bras Cardiol. 2014; 102(6):529-538

Figure 1 – Flowchart of selection of studies for inclusion in meta-analysis. DES: drug-eluting stents; RCTs: randomized controlled trials

Records identified through MEDLINE, EMBASE, Cochrane, web of science database searching

(n = 2465)

Records after duplicates removed (n = 1256)

Records screened (n = 1256)

Full-text articles assessed for elegilibilty

(n = 75)

Articles included in quantitative synthesis (meta-analysis) (n = 15 including 10 trials)

Records excluded (n = 1181)

Full-text articles excluded (n = 60)

31 non-RTCs 15 various DES comparisons2 no data on clinical characteristics Follow-up < 12 months

Additional records identified through references lists

(n = 0)

and the percentage of use of glycoprotein IIb/IIIa inhibitors, on the beneficial effect of DES in TVR, with statistically significant differences (all p <0.01, Table 2). Additionally, in sensitivity analysis omission of each trial one at a time from the analysis did not have any relevant influence on other overall results in the meta-analysis. Funnel plots were performed for all outcomes, and essential symmetry regarding overall TVR and stent thrombosis was found, which suggested that there was no publication bias in the meta-analysis.

DiscussionsThe present study revealed that no significant differences

in the incidence of all-cause death and definite/probable stent thrombosis were shown between DES and BMS in patients with STEMI during long-term follow-up. Notably, the use of the second-generation DES, EES, offered a favorable effect on reducing the risk of stent thrombosis, whereas both SES and PES did not show the clinical benefit. Moreover, compared with BMS implantation, DES implantation seemed to be associated with reduced 1-year incidence of recurrent

myocardial infarction, but the benefit did not maintain more than 2 years. Furthermore, DES showed a consistent benefit in lowering the risk of TVR during long-term observation.

Development of DES was primarily conceived to further improve clinical utility of coronary stent targeting on the potential drawback of BMS, mainly referring to the increased occurrence of in-stent restenosis. As a class of immunosuppressant and antiproliferative agent, sirolimus, paclitaxe, zotarolimus, or everolimus usually used to elute coronary stents exert potent inhibition of growth factor-induced proliferation of vascular intima and vessel smooth muscle cells29. The combination of anti-hyperplasia effect with potent mechanical support for lesion vessel wall in DES yielded a benefit in decreasing the need for repeat revascularization compared with BMS or balloon angioplasty alone during short-term follow-up30. Recently, concerns have been raised regarding the “late catch-up” phenomenon in DES, especially with “limus”-eluting stents, in unselected coronary artery diseases31. A study by Awata et al. using angioscopy showed that SES delayed reendothelialization with immature plaques and accelerated neointimal coverage

531

Original Article


Arq Bras Cardiol. 2014; 102(6):529-538

Tabl

e 1 –

Base

line p

atien

t cha

ract

erist

ics o

f ran

dom

ized

cont

rolle

d tri

als in

clude

d in

the m

eta-

analy

sis

Firs

t aut

hor,

year

Stud

y nam

eCo

mpa

rison

sNo

. en

rolle

dMe

an ag

eMa

le, %

Time f

rom

sy

mpt

om to

PCI

, m

in

Targ

et ve

ssel,

LA

D/LC

X/RC

A, %

Sten

t len

gth,

m

mDA

PT

dura

tion,

m

Use o

f GP

IIb/

IIIa in

hibito

rs,

%

Follo

w-up

, yr

sJa

ded

scor

e

van d

er H

oeve

n BL 2

008,

Atar

y JZ

2010

MISS

ION

SES

vs. B

MS15

8/152

5977

.718

954

.8/15

.7/29

.526

.412

99.6

1, 3

4

Dirks

en M

T 20

08, V

ink M

A 20

11PA

SSIO

NPE

S vs

. BMS

310/3

0961

7617

950

/8.1/3

9.919

673

.82,

54

Leibu

ndgu

t G 20

09BA

SKET

-AMI

SES

vs. B

MS75

/7462

.180

ND—

396

673

3

Lore

nzo E

D 20

09PA

SEO

PES

vs. S

ES vs

. BMS

90/90

/9062

.570

318

50.5/

24.5/

2521

610

01,

24

Saba

te M

2012

EXAM

INAT

ION

EES

vs. B

MS75

1/747

61.1

83wi

thin 4

8h40

.5/14

.5/43

.523

1252

.51

4

Spau

lding

C 20

06, 2

011

TYPH

OON

SES

vs. B

MS25

1/250

59.2

78.6

180

43.7/

14.6/

41.3

21.2

671

.51,

44

Ston

e GW

2009

HORI

ZONS

-AMI

PES

vs. B

MS22

57/74

959

.676

.522

341

/15.5/

43.5

296-

1251

.751

4

Valgi

migli

M 2

007,

Teba

ldi M

200

9 ST

RATE

GYSE

S vs

. BMS

87/88

6373

180

45/19

/3623

310

01,

2, 5

4

Valgi

migli

M 20

11MU

LTIS

TRAT

EGY

SES

vs. B

MS37

2/372

6475

.919

543

.5/15

.5/39

.321

310

03

4

Menic

helli M

2007

, Viol

ini R

2010

SESA

MISE

S vs

. BMS

160/1

6062

8024

049

.7/12

.8/37

.518

1274

.91,

33

DAPT

: dua

l ant

iplat

elet th

erap

y; EE

S: ev

eroli

mus

-elut

ing st

ents;

LAD:

left a

nter

ior de

scen

ding a

rtery

; LCX

: left c

ircum

flex a

rtery

; NA:

not a

vaila

ble; P

ES: p

aclita

xel-e

luting

sten

ts; R

CA: r

ight c

oron

ary a

rtery

; STE

MI: S

T-se

gmen

t elev

ation

m

yoca

rdial

infa

rctio

n; T

IMI: T

hrom

bolys

is In

Myo

card

ial In

farc

tion;

SES

: siro

limus

-elut

ing st

ents.

at 2-year follow-up32. As a consequence, a significant increase in late luminal loss from 2- to 4-year follow-up was indicated33. A randomized trial demonstrated a lower luminal loss at 6 months with EES compared with PES. However, this initial advantage disappeared at 3-year follow-up34, suggesting that delayed luminal loss might occur in DES. However, the profile of the unfavorable phenomenon in higher risk coronary artery diseases (e.g. STEMI) post DES implantation is now not well established. In the current study, a maintained clinical benefit of DES for more than 4 years in terms of reintervention in the previously instrumented artery with no excess of probable or definite stent thrombosis was identified in the current study. Conservatively, the beneficial result did not verify the presence of late catch-up with clinical significance in the setting of STEMI patients receiving DES treatment.

The propensity of stent thrombosis after DES implantation has raised safety concern in unselected coronary artery diseases35 . However, to date we do not know that whether the thrombosis risk of DES is higher in STEMI patients with the higher possible thrombotic coronary lesions. The implantation of DES in ruptured plaques with a large necrotic core (the lesion substrate responsible for most cases of STEMI) might impair vascular healing responses, and potentially result in increased rates of stent thrombosis36 . However, a previous meta-analysis comparing DES versus BMS for acute coronary syndromes did not show an evidence of significantly increased risk of stent thrombosis associated with DES implantation37. Similarly, the current study did not show the significant increase in fatal thrombotic evens and all-cause death associated with DES placement in STEMI patients. Even in a special class of DES, mainly referring to EES, a favorable effect in reducing the risk of stent thrombosis was shown at long-term follow-up. The finding was consistent with the result from a previous large-scale meta-analysis in unselected coronary artery diseases, indicating that EES treatment had the lower rate of stent thrombosis within 2 years of stent implantation than BMS38. Causally, STEMI was characterized by the more possible thrombotic coronary lesions than non-ST segment elevation acute coronary syndrome or stable coronary artery diseases. As thus, we presumed that, in terms of lowering the risk of stent thrombosis, EES might have the more superiority in patients with higher possible thrombotic lesions. Additionally, a favorable tendency toward reduce the risk of recurrent myocardial infarction was achieved in DES treatment group in the first year follow-up, but the potential benefit did not maintain during the longer-term observation. It was notable that the trend of reinfarction related to DES placement was presented substantially consistent with that of stent thrombosis, the risk of which appeared to be lower at 1-year follow-up. The potential benefit of DES in lowering the rate of reinfarction might partially result from their favorable trend to reducing the risk of stent thrombosis.

Methodologically, the use of random-effect model, no publication bias, and relatively low statistical heterogeneities among the included trials corrected the inherent drawback and provided reassurance for making a robust conclusion. Moreover, sensitivity analyses further confirmed the credibility

532

Original Article

Arq Bras Cardiol. 2014; 102(6):529-538


Figure 2 – Pooled risk ratios of DES versus BMS for all-cause mortality. BMS: bare-metal stents; CI: confidence intervals; DES: drug-eluting stents; M–H: Mantel-Haenszel.

of the meta-analysis estimates. However, it was worthwhile notable that this meta-analysis investigated the long-term clinical outcomes of DES versus BMS in patients with STEMI, the results of which cannot be automatically extrapolated to non-ST-segment elevation acute coronary syndrome. In addition, the power in subgroup analysis on ≥2-year follow-up data might be restricted by the limited study number, and the conclusions should be made carefully. Therefore, more studies with longer-term observation are required to further

verify the findings and conclusions in the subgroup analyses of the current study.

ConclusionsThis present study has identified the persistent benefit

of DES on reducing the need for repeat revascularization in patients with STEMI at long-term follow-up. Although DES did not offer a benefit in reducing all-cause mortality

533

Original Article

Arq Bras Cardiol. 2014; 102(6):529-538


Figure 3 – Pooled risk ratios of DES versus BMS for definite or probable stent thrombosis. BMS: bare-metal stents; CI: confidence intervals; DES: drug-eluting stents; M–H: Mantel-Haenszel.

compared with BMS, the procedure did not increase the risk of stent thrombosis, and even EES might markedly decrease the malignant clinical occurrence in these specific patients with the higher possible thrombotic coronary lesions. In addition, DES seems to be as safe as BMS, without

evidence of any increased long-term risk of all-cause death and recurrent myocardial infarction. The current study, a meta-analysis based on the newest available data from RCTs comparing DES versus BMS in patients with STEMI, offers important insights into the relative safety and efficacy of DES.

534

Original Article

Arq Bras Cardiol. 2014; 102(6):529-538


Figure 4 – Pooled risk ratios of DES versus BMS for recurrent myocardial infarction. BMS: bare-metal stents; CI: confidence intervals; DES: drug-eluting stents; M–H: Mantel-Haenszel.

535

Original Article

Arq Bras Cardiol. 2014; 102(6):529-538


Figure 5 – Pooled risk ratios of DES versus BMS for target vessel revascularization. BMS: bare-metal stents; CI: confidence intervals; DES: drug-eluting stents; M–H: Mantel-Haenszel.

536

Original Article

Arq Bras Cardiol. 2014; 102(6):529-538


1. De Luca G, Suryapranata H, Stone GW, Antoniucci D, Biondi-Zoccai G, Kastrati A, et al. Coronary stenting versus balloon angioplasty for acute myocardial infarction: a meta-regression analysis of randomized trials. Int J Cardiol. 2008;126(1):37-44.

2. Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, et al; Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Investigators. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med. 2002;346(13):957-66.

3. Sabate M, Cequier A, Iniguez A, Serra A, Hernandez-Antolin R, Mainar V, et al. Everolimus-eluting stent versus bare-metal stent in ST-segment elevation myocardial infarction (EXAMINATION): 1 year results of a randomised controlled trial. Lancet. 2012;380(9852):1482-90.

4. Di Lorenzo E, De Luca G, Sauro R, Varricchio A, Capasso M, Lanzillo T, et al. The PASEO (PaclitAxel or Sirolimus-Eluting Stent Versus Bare Metal Stent in Primary Angioplasty) Randomized Trial. JACC Cardiovasc Interv. 2009;2(6):515-23.

5. Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 2005;293(17):2126-30.

6. Daemen J, Tanimoto S, Garcia-Garcia HM, Kukreja N, van de Sande M, Sianos G, et al. Comparison of three-year clinical outcome of sirolimus- and paclitaxel-eluting stents versus bare metal stents in patients with ST-segment

elevation myocardial infarction (from the RESEARCH and T-SEARCH Registries). Am J Cardiol. 2007;99(8):1027-32.

7. Kaltoft A, Kelbaek H, Thuesen L, Lassen JF, Clemmensen P, Klovgaard L, et al. Long-term outcome after drug-eluting versus bare-metal stent implantation in patients with ST-segment elevation myocardial infarction: 3-year follow-up of the randomized DEDICATION (Drug Elution and Distal Protection in Acute Myocardial Infarction) Trial. J Am Coll Cardiol. 2010;56(8):641-5.

8. Piscione F, Piccolo R, Cassese S, Galasso G, De Rosa R, D’Andrea C, et al. Effect of drug-eluting stents in patients with acute ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: a meta-analysis of randomised trials and an adjusted indirect comparison. EuroIntervention. 2010;5(7):853-60.

9. Stone GW, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, et al; HORIZONS-AMI Trial Investigators. Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction (HORIZONS-AMI): final 3-year results from a multicentre, randomised controlled trial. Lancet. 2011;377(9784):2193-204.

10. De Luca G, Stone GW, Suryapranata H, Laarman GJ, Menichelli M, Kaiser C, et al. Efficacy and safety of drug-eluting stents in ST-segment elevation myocardial infarction: a meta-analysis of randomized trials. Int J Cardiol. 2009;133(2):213-22.

References

Table 2 – Subgroup analyses on target vessel revascularization and in-stent thrombosis

Subgroups No. of patientsTVR Stent thrombosis

RR (95% CI) p value RR (95% CI) P value

SES 2364 0.50 [0.40, 0.63] < 0.001 1.12 [0.78, 1.60] 0.54

PES 3805 0.62 [0.44, 0.88] 0.007 0.98 [0.67, 1.46] 0.94

EES 1498 0.55 [0.35, 0.86] 0.008 0.37 [0.15, 0.87] 0.02

Pain to angioplasty ≤ 3h 1295 0.57 [0.42, 0.76] 0.0002 1.00 [0.60, 1.65] 0.99

Pain to angioplasty > 3h 6133 0.54 [0.44, 0.67] < 0.001 0.90 [0.63, 1.28] 0.55

DAPT duration ≤ 6 m 2450 0.51 [0.39, 0.67] < 0.001 1.11 [0.77, 1.60] 0.56

DAPT duration > 6 m 5127 0.60 [0.49, 0.75] < 0.001 0.81 [0.49, 1.33] 0.40

Use of GP IIb/IIIa inhibitors ≥ 90% 1491 0.43 [0.32, 0.58] < 0.001 1.13 [0.71, 1.80] 0.61

Use of GP IIb/IIIa inhibitors < 90% 6086 0.62 [0.52, 0.74] < 0.001 0.89 [0.63, 1.27] 0.52

CI: confidence interval; DAPT: dual antiplatelet therapy; EES: everolimus-eluting stents; GP: glycoprotein; PES: paclitaxel-eluting stents; RR: risk ratios; SES: sirolimus-eluting stents; TVR: target vessel revascularization.

Author contributionsConception and design of the research: Wang S;

Acquisition of data: Wang L, Wang H; Analysis and interpretation of the data: Wang L, Wang H, Li Z, Wang Y; Obtaining financing: Dong P; Writing of the manuscript: Wang L, Wang H, Wang Y; Critical revision of the manuscript for intellectual content: Dong P, Duan N, Zhao Y, Wang S.

Potential Conflict of InterestNo potential conflict of interest relevant to this article

was reported.

Sources of FundingThere were no external funding sources for this study.

Study AssociationThis study is not associated with any thesis or dissertation work.

537

Original Article

Arq Bras Cardiol. 2014; 102(6):529-538


11. Dibra A, Tiroch K, Schulz S, Kelbaek H, Spaulding C, Laarman GJ, et al. Drug-eluting stents in acute myocardial infarction: updated meta-analysis of randomized trials. Clin Res Cardiol. 2010;99(6):345-57.

12. Juni P, Witschi A, Bloch R, Egger M. The hazards of scoring the quality of clinical trials for meta-analysis. JAMA. 1999;282(11):1054-60.

13. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1-12.

14. Ioannidis JP, Patsopoulos ND, Evangelou E. Uncertainty in heterogeneity estimates in meta-analyses. BMJ. 2007;335(7626):914-6.

15. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.

16. Atary JZ, van der Hoeven BL, Liem SS, Jukema JW, van der Bom JG, Atsma DE, et al. Three-year outcome of sirolimus-eluting versus bare-metal stents for the treatment of ST-segment elevation myocardial infarction (from the MISSION! Intervention Study). Am J Cardiol. 2010;106(1):4-12.

17. Dirksen MT, Vink MA, Suttorp MJ, Tijssen JG, Patterson MS, Slagboom T, et al; Paclitaxel-Eluting Stent versus Conventional Stent; in Myocardial Infarction with ST-Segment Elevation (PASSION) investigators. Two year follow-up after primary PCI with a paclitaxel-eluting stent versus a bare-metal stent for acute ST-elevation myocardial infarction (the PASSION trial): a follow-up study. EuroIntervention. 2008;4(1):64-70.

18. Leibundgut G, Nietlispach F, Pittl U, Brunner-La Rocca H, Kaiser CA, Pfisterer ME. Stent thrombosis up to 3 years after stenting for ST-segment elevation myocardial infarction versus for stable angina--comparison of the effects of drug-eluting versus bare-metal stents. Am Heart J. 2009;158(2):271-6.

19. Menichelli M, Parma A, Pucci E, Fiorilli R, De Felice F, Nazzaro M, et al. Randomized trial of Sirolimus-Eluting Stent Versus Bare-Metal Stent in Acute Myocardial Infarction (SESAMI). J Am Coll Cardiol. 2007;49(19):1924-30.

20. Spaulding C, Henry P, Teiger E, Beatt K, Bramucci E, Carrie D, et al; TYPHOON Investigators. Sirolimus-eluting versus uncoated stents in acute myocardial infarction. N Engl J Med. 2006;355(11):1093-104.

21. Spaulding C, Teiger E, Commeau P, Varenne O, Bramucci E, Slama M, et al. Four-year follow-up of TYPHOON (trial to assess the use of the CYPHer sirolimus-eluting coronary stent in acute myocardial infarction treated with BallOON angioplasty). JACC Cardiovasc Interv. 2011;4(1):14-23.

22. Stone GW, Lansky AJ, Pocock SJ, Gersh BJ, Dangas G, Wong SC, et al; HORIZONS-AMI Trial Investigators. Paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction. N Engl J Med. 2009;360(19):1946-59.

23. Tebaldi M, Arcozzi C, Campo G, Percoco G, Ferrari R, Valgimigli M; STRATEGY Investigators. The 5-year clinical outcomes after a randomized comparison of sirolimus-eluting versus bare-metal stent implantation in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2009;54(20):1900-1.

24. Valgimigli M, Campo G, Arcozzi C, Malagutti P, Carletti R, Ferrari F, et al. Two-year clinical follow-up after sirolimus-eluting versus bare-metal stent implantation assisted by systematic glycoprotein IIb/IIIa Inhibitor Infusion in patients with myocardial infarction: results from the STRATEGY study. J Am Coll Cardiol. 2007;50(2):138-45.

25. Valgimigli M, Campo G, Gambetti S, Bolognese L, Ribichini F, Colangelo S, et al; MULTIcentre evaluation of Single high-dose bolus TiRofiban versus Abciximab with sirolimus eluting sTEnt or Bare Metal Stent in Acute Myocardial Infarction studY Investigators. Three-year follow-up

of the MULTIcentre evaluation of Single high-dose Bolus TiRofiban versus Abciximab with Sirolimus-eluting STEnt or Bare-Metal Stent in Acute Myocardial Infarction StudY (MULTISTRATEGY). Int J Cardiol. 2013;165(1):134-41.

26. van der Hoeven BL, Liem SS, Jukema JW, Suraphakdee N, Putter H, Dijkstra J, et al. Sirolimus-eluting stents versus bare-metal stents in patients with ST-segment elevation myocardial infarction: 9-month angiographic and intravascular ultrasound results and 12-month clinical outcome results from the MISSION Intervention Study. J Am Coll Cardiol. 2008;51(6):618-26.

27. Vink MA, Dirksen MT, Suttorp MJ, Tijssen JG, van Etten J, Patterson MS, et al. 5-year follow-up after primary percutaneous coronary intervention with a paclitaxel-eluting stent versus a bare-metal stent in acute ST-segment elevation myocardial infarction: a follow-up study of the PASSION (Paclitaxel-Eluting Versus Conventional Stent in Myocardial Infarction with ST-Segment Elevation) trial. JACC Cardiovasc Interv. 2011;4(1):24-9.

28. Violini R, Musto C, De Felice F, Nazzaro MS, Cifarelli A, Petitti T, et al. Maintenance of long-term clinical benefit with sirolimus-eluting stents in patients with ST-segment elevation myocardial infarction 3-year results of the SESAMI (sirolimus-eluting stent versus bare-metal stent in acute myocardial infarction) trial. J Am Coll Cardiol. 2010;55(8):810-4.

29. Schomig A, Kastrati A, Wessely R. Prevention of restenosis by systemic drug therapy: back to the future? Circulation. 2005;112(18):2759-61.

30. Stefanini GG, Holmes DR Jr. Drug-eluting coronary-artery stents. N Engl J Med. 2013;368(3):254-65.

31. Sheiban I, Chiribiri A, Galli S, Biondi-Zoccai G, Montorsi P, Beninati S, et al. Sirolimus-eluting stent implantation for bare-metal in-stent restenosis: is there any evidence for a late catch-up phenomenon? J Cardiovasc Med (Hagerstown). 2008;9(8):783-8.

32. Awata M, Kotani J, Uematsu M, Morozumi T, Watanabe T, Onishi T, et al. Serial angioscopic evidence of incomplete neointimal coverage after sirolimus-eluting stent implantation: comparison with bare-metal stents. Circulation. 2007;116(8):910-6.

33. Sousa JE, Costa MA, Abizaid A, Feres F, Seixas AC, Tanajura LF, et al. Four-year angiographic and intravascular ultrasound follow-up of patients treated with sirolimus-eluting stents. Circulation. 2005;111(18):2326-9.

34. Garg S, Serruys P, Onuma Y, Dorange C, Veldhof S, Miquel-Hebert K, et al; SPIRIT II Investigators. 3-year clinical follow-up of the XIENCE V everolimus-eluting coronary stent system in the treatment of patients with de novo coronary artery lesions: the SPIRIT II trial (Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions). JACC Cardiovasc Interv. 2009;2(12):1190-8.

35. Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med. 2007;356(10):998-1008.

36. de la Torre-Hernandez JM, Alfonso F, Hernandez F, Elizaga J, Sanmartin M, Pinar E, et al; ESTROFA Study Group. Drug-eluting stent thrombosis: results from the multicenter Spanish registry ESTROFA (Estudio ESpanol sobre TROmbosis de stents FArmacoactivos). J Am Coll Cardiol. 2008;51(10):986-90.

37. Greenhalgh J, Hockenhull J, Rao N, Dundar Y, Dickson RC, Bagust A. Drug-eluting stents versus bare metal stents for angina or acute coronary syndromes. Cochrane Database Syst Rev. 2010 May 12;(5):CD004587.

38. Palmerini T, Biondi-Zoccai G, Della Riva D, Stettler C, Sangiorgi D, D’Ascenzo F, et al. Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis. Lancet. 2012; 379(9824):1393-402.

538

Original Article

Applicability of Two International Risk Scores in Cardiac Surgery in a Reference Center in BrazilSilvia Bueno Garofallo, Daniel Pinheiro Machado, Clarissa Garcia Rodrigues, Odemir Bordim Jr., Renato A. K. Kalil, Vera Lúcia PortalPost-Graduation Program in Health Sciences: Cardiology, Instituto de Cardiologia/Fundação Universitária de Cardiologia, Porto Alegre, RS - Brazil

Mailing Address: Vera Lúcia Portal •Av. Princesa Isabel, 370, Santana. Postal Code 90.620-000, Porto Alegre, RS - BrazilE-mail: [email protected] received November 30, 2013; Manuscript revised January 31, 2014; accepted February 06, 2014.

DOI: 10.5935/abc.20140064

Abstract

Background: The applicability of international risk scores in heart surgery (HS) is not well defined in centers outside of North America and Europe.

Objective: To evaluate the capacity of the Parsonnet Bernstein 2000 (BP) and EuroSCORE (ES) in predicting in-hospital mortality (IHM) in patients undergoing HS at a reference hospital in Brazil and to identify risk predictors (RP).

Methods: Retrospective cohort study of 1,065 patients, with 60.3% patients underwent coronary artery bypass grafting (CABG), 32.7%, valve surgery and 7.0%, CABG combined with valve surgery. Additive and logistic scores models, the area under the ROC (Receiver Operating Characteristic) curve (AUC) and the standardized mortality ratio (SMR) were calculated. Multivariate logistic regression was performed to identify the RP.

Results: Overall mortality was 7.8%. The baseline characteristics of the patients were significantly different in relation to BP and ES. AUCs of the logistic and additive BP were 0.72 (95% CI, from 0.66 to 0.78 p = 0.74), and of ES they were 0.73 (95% CI; 0.67 to 0.79 p = 0.80). The calculation of the SMR in BP was 1.59 (95% CI; 1.27 to 1.99) and in ES, 1.43 (95% CI; 1.14 to 1.79). Seven RP of IHM were identified: age, serum creatinine > 2.26 mg/dL, active endocarditis, systolic pulmonary arterial pressure > 60 mmHg, one or more previous HS, CABG combined with valve surgery and diabetes mellitus.

Conclusion: Local scores, based on the real situation of local populations, must be developed for better assessment of risk in cardiac surgery. (Arq Bras Cardiol. 2014; 102(6):539-548)

Keywords: Thoracic surgery / mortality; Risk Factors; Information services; Brazil.

IntroductionCurrently, there are more than 20 models of risk scores in

cardiac surgery1-5 . Among the best known are the Parsonnet score, STS risk score, Higgins score, Northern New England score (NNE score), Ambler score, Bernstein-Parsonnet 2000 score and EuroSCORE. The Bernstein Parsonnet 2000 (BP) and EuroSCORE (ES) are differentiated, as they can be used for bypass surgery, valve surgery, or both, plus the capacity to be applied at the bedside. The Parsonnet score was developed in 1989 and is notable for having been a pioneer in systematic risk stratification in cardiac surgery and applicable to different populations1. The Bernstein Parsonnet 2000 corresponds to the revised and simplified Parsonnet score, based on a database of 10,703 patients in New Jersey, in the United States, between 1994 and 19952.

The EuroSCORE (European System for Cardiac Operative Risk Evaluation) is currently one of the most commonly used scores. It was developed from data on 19,030 patients in Europe, in 19956-10. In 2011, the EuroSCORE was revised based on data from approximately 32,000 patients and called EuroSCORE II. Although it was already possible to use it through its official website (www.euroscore.org), the article containing its validation was not available at the time of our article’s review.

Both scores are shown in the additive and logistic models. The additive model is more easily applicable. However, the logistic model is more discriminating in high-risk patients5,11,12. One should consider, when evaluating a risk score, its capacity to accurately estimate the in-hospital mortality, in addition to the discriminatory power4,13,14.

In Brazil, data show that postoperative mortality in cardiac surgery is still high6,7. This can be explained in part by the socioeconomic inequalities of our population8 and because the few tertiary centers performing large volumes of cardiac surgeries per year are located in the richest regions of the country6,9.

Given the different characteristics of the population and the scarcity of national scores, we aimed to test the applicability of

539

Original Article

Garofallo et al.Risk Scores in Cardiac Surgery

Arq Bras Cardiol. 2014; 102(6):539-548

BP and ES in patients undergoing cardiac surgery in southern Brazil and to identify risk factors.

MethodsA retrospective cohort of patients older than 18 years of

age, treated at the Instituto de Cardiologia do Rio Grande do Sul (IC/FUC) from January 2007 to July 2008, submitted to coronary artery bypass graft (CABG) surgery, valve surgery or CABG combined with valve surgery was assessed. Patients with pathologies of the aorta exclusively, congenital heart disease and heart transplants were excluded. The sample consisted of 1,065 patients.

IC/FUC is a reference tertiary care center in cardiology in southern Brazil, where approximately 2,000 heart surgeries are performed each year, including congenital heart surgery, transplants, pacemakers and cardioverter-defibrillator implants, as well as aortic surgery, among others.

Medical records were reviewed manually by the authors. Almost all of the variables in the assessed risk scores were in the charts, which included the standardized preoperative evaluation form, always filled out by the same medical team. Data from anesthetic records and information on postoperative intensive care unit admission were also extracted.

However, information on the specific degree of severity of chronic obstructive pulmonary disease (COPD) and the degree of sequelae after a neurological event were rarely available. The definition of COPD used in the BP score was the same used in the ES, as there is no available definition of this variable in the BP. Patients were considered as having severe COPD only when FEV1 < 50% of the predicted at the spirometry10. Neurological dysfunction was considered as any prior neurological event (cerebrovascular accident [CVA] or transient ischemic attack [TIA]). Congestive heart failure was considered present in patients with functional class III or IV according to the New York Heart Association (NYHA).

Data were recorded on a specific form and typed in by the authors in Microsoft Office Excel database.

One hundred and fifty-three patients had no preoperative assessment of the left ventricular ejection fraction (LVEF) and 22 had no serum creatinine level measurements. The amount of missing data, which accounted for 14% of the data, was statistically included using SPSS version 19.0 by multiple imputation13,14.

The assessed outcome was in-hospital mortality (IHM), defined as death from any cause, both during surgery and in the postoperative period, before discharge.

Statistical Analysis The difference between proportions of independent

samples was calculated to compare prevalence in the sample and in the scores’ populations. Pearson’s chi-square test was used to compare risk factors in relation to clinical outcomes. Odds ratio (OR) and 95% confidence interval (95%CI) were used to calculate the magnitude of the effect. The level of significance was set at α = 0.05. SPSS software version 19.0 and PEPI 4.0 were used for the statistical analyses.

Multivariate logistic regression models were applied to the sample to identify independent mortality predictors of the scores. The variables assessed in two scores that showed higher prevalence than 2% in the sample were included, as suggested by Parsonnet et al1, such as age, gender, diabetes mellitus, hypertension, previous heart surgery, more than one previous heart surgery, aortic valve replacement, mitral valve replacement, valve surgery combined with CABG, pulmonary hypertension, active endocarditis, serum creatinine, ejection fraction, left main coronary lesion, carotid artery disease, peripheral vascular disease and neurological disease.

The scores were applied to the sample in their additive and logistic forms, according to the algorithms of the original articles. In the BP score, the sample was divided into deciles and mortality was assessed in each decile so it would be possible to compare it with the ES, as the latter is presented as risk groups (low, medium and high risk). In the BP, a score of 0-3 was considered low risk, 3.1 to 17.5, medium risk, and ≥ 17.5, high risk. In the ES, a score of 0-2 was considered low risk, 3-5, medium risk, and ≥ 6, high risk.

The sco re accuracy was a s se s sed us ing the Hosmer-Lemeshow test, which compares the observed and expected mortality rates in same-size deciles. The difference between observed and expected mortality rates was also assessed by the standardized mortality ratio (SMR), which is obtained dividing the observed mortality by the expected one and confidence intervals, calculated as suggested by Breslow & Day15. The H-L test is considered the most adequate to evaluate the differences between the observed and expected mortalities; however, we also chose to use the SMR, as it is possible to apply it to risk groups.

The ROC (Receiver Operating Characteristic) curve evaluated the discriminatory power of the scores and the areas under the ROC curve (AUC) - C statistics - of both models; they were compared using STATA 9.2 software in their additive and logistic forms. The software was also used for chart preparation.

Ethical Considerations The study was submitted to the analysis and approval by

the Research Ethics Committee of Instituto de Cardiologia do RS, according to resolution of the National Health Council.

The researchers undertake to comply with the rules of Resolution 196/96 of the National Health Council, referenced in IV.1-g ("the guarantee of confidentiality that guarantees the privacy of subjects regarding confidential data involved in the research").

ResultsThe mean age was 61.4 years (± 11.8 years), 38% were

women, 60.3% of patients underwent CABG, 32.7%, valve surgery, and 7.0%, CABG combined with valve surgery.

The sample overall mortality rate was 7.8%. Patients undergoing CABG had a mortality rate of 5.9%. In valve surgery (aortic and/or mitral and/or tricuspid), mortality was 8.6% and in CABG associated with valve surgery, 20.0%. Mean mortality

540

Original Article


Arq Bras Cardiol. 2014; 102(6):539-548

in the original BP and ES were 5.3% and 4.7%, respectively. The mean BP score in the sample was 14.69 (minimum zero and maximum 84.5) and in the ES, 4.52 (minimum zero and maximum 16).

Baseline characteristics of patients were significantly different from those of the BP and ES populations (Tables 1, 2 and 3). In relation to BP, our sample had a predominance of the female gender and higher prevalence of arterial hypertension, pulmonary hypertension, asthma, morbid obesity, left main coronary artery lesion and previous heart surgery. Aortic, mitral and tricuspid valve surgery were also more frequent. The number of patients with preoperative intra-aortic balloon was significantly lower in our population. Regarding the ES, the female gender also predominated in our sample. We observed a higher prevalence of COPD, neurological dysfunction, previous heart surgery, unstable angina and pulmonary hypertension.

AUCs of the additive and logistic BP were 0.72 (95% CI: 0.66-0.78), and AUCs of additive and logistic ES were 0.73 (95%CI: 0.67-0.78). There was no statistically significant difference when comparing the AUCs of additive (p = 0.74) and logistic (p = 0.80) models of the two risk scores (Figures 1 and 2).

The Hosmer-Lemeshow (HL) test showed poor score calibration: x² = 87.61 (8 gl), p < 0.001 in BP and x² = 24.20 (8 gl), p = 0.01 in the ES. The calculation of the overall SMR

showed that the scores tend to underestimate mortality in the sample, whereas in the additive and logistic BP SMR was 1.59 (95% CI: 1.27 to 1.99). In the additive and logistic ES, the SMR was 1.43 (95% CI: 1.14 to 1.79) - Tables 4 and 5.

In the multivariate logistic regression (Table 6), the following showed to be independent risk predictors for in-hospital mortality: diabetes mellitus (OR = 2.28; 95%CI: 1.34 to 3.88), CABG combined with valve surgery (OR = 2.38; 95% CI: 1.18 to 4.80), age between 76 and 79 years (OR = 2.49; 95%CI: 1.12 to 5.54), previous heart surgery (OR = 2.68; 95%CI: 1.40 to 5.12), two or more previous heart surgeries (OR = 3.34; 95% CI: 1.16 to 9.63), systolic pulmonary artery pressure (sPAP)> 60 mmHg (OR = 3.44; 95%CI: 1.60 to 7.39), age > 80 years (OR = 3.61; 95%CI: 1.54 to 8.45), active endocarditis (OR = 4.388; 95%CI: 1.00 to 19.17) and serum creatinine > 2.26 mg/dL (OR = 4.71; 95%CI: 1.28 to 17.34).

DiscussionIn our sample, a North-American score (Bernstein

Parsonnet 2000) and a European one (EuroSCORE) showed good discriminatory power, but underestimated the in-hospital mortality. This result contradicts what has been observed when applying BP and ES in developed countries. In a systematic review of the applicability of the ES in cardiac surgery, six

Table 1 – Prevalence of risk factors in the sample and in the Bernstein Parsonnet 2000 population

Risk factorPrevalence in sample

(%)(n = 1,065)

Prevalence in BP(%)

(n = 10,703)p value

Female gender 38.7 31.3 < 0.001

Age70-7576-79> 80

14.76.74.7

18.013.77.8

< 0.001< 0.001< 0.001

Diabetes mellitus 23.6 29.4 < 0.001

LVEF> 50%30-49%< 30%

15.84.8

38.28.4

< 0.001< 0.001

Arterial hypertension 73.1 63.1 < 0.001

Congestive heart failure 19.4 18.9 0.720

Morbid obesity 19.6 8.9 < 0.001

Severe COPD 0.1 2.5 < 0.001

Previous heart surgeryTwo or more previous heart surgeries

10.0

2.1

7.0

0.4

0.001

< 0.001

Aortic valve replacement 18.8 12.1 < 0.001

Mitral valve replacement 13.4 7.1 < 0.001

CABG with valvular surgery 7.0 8.5 0.093

LMC lesion 23.8 16.9 < 0.001

Preoperative IAB 0.6 8.7 < 0.001

LMC: Left main coronary; IAB: Intra-aortic balloon; BP: Bernstein Parsonnet 2000; CABG: Coronary artery bypass surgery; COPD: Chronic obstructive pulmonary disease; LVEF: Left ventricular ejection fraction.

541

Original Article


Arq Bras Cardiol. 2014; 102(6):539-548

studies from Japan, Belgium, France, Turkey and the UK were included, involving 16,000 patients. The additive ES was applied and it was observed that in patients with ES < 6, mortality was overestimated, while in patients with ES > 10, it was underestimated16. When validating the ES in Australia17, in 8,331 patients undergoing cardiac surgery, the expected overall mortality rate for this population was 5.31% for the additive model and 8.76% for the logistic model, while the observed mortality was 3, 20%. In Germany18, in 26,501 patients undergoing isolated CABG, the expected mortality at the logistic ES was 5.2%, while the observed one was 2.6%.

The BP score has been previously compared with ES. In 2006, a prospective study carried out in Tel Aviv by Berman et al19 compared the additive forms of the two scores in a sample of 1,639 patients undergoing cardiac surgery. The mortality rate in this population was 4.83%. The patients were divided into five risk groups. In the BP: 0 to 10; 10.5 to 20; 20.5 to 30; 30.5 to 40 and > 40. In the ES: 0 to 2; 3 to 5; 6 to 8; 9 to 11 and > 12. There were no

significant differences between the observed and expected mortalities in both scores. The AUC was 0.83 in BP and 0.73 in ES. In 2004, the work by Syed et al20 compared the initial BP score with ES using retrospective data from only 194 patients undergoing cardiac surgery at a single center in Saudi Arabia. The AUC was 0.685 in BP and 0.766 in ES.

In Brazil, there are few records on the profile of patients undergoing cardiac surgery. The available data are recorded by the Hospital Information System of the Unified Health System, which does not include clinical data. In 2006, Ribeiro et al6 performed a review of available data in Datasus related to 115,021 cardiac surgeries performed between 2000 and 2003. Prevalence of isolated CABG was 57.1%, and of valve replacement, 33.7%. Overall mortality was 8.0% in this sample, of which 7.0% in patients submitted to CABG, 8.9% in those undergoing valve replacement and 16.5% in those submitted to complex cardiac surgery.

The multivariate analysis showed higher mortality among older patients, women, those submitted to valve and/or

Table 2 – Prevalence of risk factors in the sample and in the Bernstein Parsonnet 2000 population

Exceptional situationsPrevalence in sample

(%)(n = 1,065)

Prevalence in BP(%)

(n = 10,703)p value

Cardiogenic shock 0.8 1.8 0.017

Active Endocarditis 1.0 0.4 0.005

Treated Endocarditis 0.8 0.8 0.915

LV aneurysm surgery 0.8 0.5 0.194

Tricuspid valve surgery 1.6 0.4 < 0.001

Pace-maker dependence 1.3 1.5 0.604

VT/VF 0.5 3.3 0.03

Asthma 7.9 2.5 < 0.001

Preoperative OTI 0.5 1.3 0.017

Pulmonary hypertension 16.6 10.7 <0.001

Cirrhosis 0 0.2 <0.001

Dialysis 0.5 0.9 0.151

Acute or chronic renal failure 5.1 4.6 0.457

Asymptomatic abdominal aortic aneurysm 0.8 1.3 0.128

Carotid disease (bilateral or unilateral occlusion) 3.0 2.6 0.612

Peripheral vascular disease 6.9 9.1 0.013

Previous transfusion reaction 0 0.2 < 0.001

Severe neurological disease (paraplegia, hemiparesis, muscular dystrophy) 7.6 8.4 0.364

Unsuccessful PTCA 1.2 2.3 0.014

Drug abuse 0 2.1 < 0.001

AMI < 48 h 0.9 5.4 < 0.001

Acute VSD 0.1 -- --

Idiopathic thrombocytopenic purpura 0 0.3 < 0.001

PTCA: Percutaneous transluminal coronary angioplasty; BP: Bernstein Parsonnet 2000; VSD: Ventricular septal defect (no cases in the sample); AMI: Acute myocardial infarction; Preoperative OTI: Preoperative orotracheal intubation; VT / VF: Ventricular tachycardia / ventricular fibrillation; LV: Left ventricle.

542

Original Article


Arq Bras Cardiol. 2014; 102(6):539-548

Table 3 – Prevalence of risk factors in the sample and in the EuroSCORE population

Risk factorsPrevalence in sample

(%)(n = 1.065)

Prevalence in EuroSCORE(%)

(n = 19.030)p value

Age (for each 5 years > 60 years)< 6060-6465-6970-74> 75

40.816.716.612.613.3

33.217.820.717.99.6

< 0.0010.314

< 0.001< 0.001< 0.001

Female gender 38.7 27.8 < 0.001

COPD 7.9 3.9 < 0.001

Extra-cardiac arteriopathy 9.0 11.3 0.019

Neurological dysfunction 5.7 1.4 < 0.001

Previous heart surgery 11.9 7.3 < 0.001

Serum creatinine >2.26 mg/dL 1.4 1.8 0.344

Active endocarditis 1.0 1.1 0.034

Critical preoperative status 2.7 4.1 0.022

Unstable Angina 17.1 8.0 < 0.001

LVEF= 30-50%LVEF < 30%

15.84.8

25.65.8

< 0.0010.168

AMI < 90 days 1.2 9.7 < 0.001

Pulmonary hypertension (sPAP > 60 mmHg) 5.2 2.0 < 0.001

Emergency heart surgery 1.2 4.9 < 0.001

Another heart surgery associated or not to CABG CABG 39.7 36.4 0.029

Surgery involving thoracic aorta 2.3 2.4 0.834

VSD post-AMI 0.1 0.2 0.467

VSD: Ventricular Septal Defect; CABG: Coronary artery bypass surgery; COPD: Chronic obstructive pulmonary disease; LVEF: Left ventricular ejection fraction; AMI: Acute myocardial infarction; sPAP: Systolic pulmonary artery pressure.

1.00

0.75

0.50

0.25

0.00

Sens

itivity

0.00 0.25 0.501-Specificity

Parsonnet (AUC=0.73) Euroscore (AUC=0.73)

0.75 1.00

Figure 1 – Comparison of areas under the ROC curve of logistic Bernstein Parsonnet 2000 and EuroSCORE - STATA 9.2 software. AUC of the logistic Bernstein Parsonnet 2000, 0.73 (95%CI: 0.66 to 0.78) and logistic EuroSCORE, 0.73 (95%CI: 0.67-0.78). Chi-square = 0.06, p (x2) = 0.79.

543

Original Article


Arq Bras Cardiol. 2014; 102(6):539-548

complex surgeries and patients admitted to hospitals with fewer surgeries. In hospitals that performed 1-130 surgeries a year, mortality was 9.7%, while in those that performed more than 341 surgeries a year, mortality was 5.8%. Previous studies had already shown an inverse association between the number of procedures performed a year and mortality21.

Compared to the United States, Brazil performs almost six times fewer surgeries per 100,000 inhabitants/year. Another review of Datasus data7 showed that in the years 2005, 2006 and 2007, 63,529 isolated CABG surgeries were performed in 191 hospitals. The recorded in-hospital mortality was 6.22%. The regions with higher number of

procedures, which are also the wealthiest ones and the ones that have the highest number of referral centers, tend to have lower mortality. For instance, whereas in the southern region 15,985 procedures were performed with a mortality of 6.52%, in the northern region, 1,354 procedures were carried out, with a mortality rate of 7.24%.

We believe it is very important to study the variables that involve surgery in Brazil, considering that the postoperative mortality is even higher when compared to Europe and the United States. The overall mortality rate in the sample was 7.8%, close to the observed mortality in SUS6, whereas in the BP population, it was 5.3%, and in the ES, 4.7%.

Table 4 – Observed and expected mortality in the additive and logistic Bernstein Parsonnet 2000 in risk groups

Expected mortality Observed mortality SMR

BP N N % N % Estimate LL UL

Additive

0 a 3 157 1 0.7 3 1.9 2.7 0.5 8.1

3.1 a 17.5 596 10 1.7 28 4.7 2.7 1.8 4.0

> 17.5 311 41 13.21 52 16.7 1.3 0.9 1.7

Total 1.064 52 4. 83 7.8 1.6 1.3 1.9

Logistic BP

≤ 0.0137 399 4 0.9 12 3.0 3.2 1.7 5.6

0.0138 a 0.0304 335 7 2.0 19 5.7 2.8 1.7 4.3

> 0.0304 338 42 12.6 52 15.8 1.2 0.9 1.6

Total 1.064 52 4.9 83 7.8 1.6 1.3 1.9

LL: Lower limit; UL: Upper limit; SMR: Standardized Mortality Rate.

0,00 0.25 0.501-Specificity

0.75 1.00

1.00

0.75

0.50

0.25

0.00

Sens

itivity

Parsonnet (AUC=0.73) Euroscore (AUC=0.73)

Figure 2 – Comparison of areas under the ROC curve of additive Bernstein Parsonnet 2000 and EuroSCORE - STATA 9.2 software. AUC of additive Bernstein Parsonnet 2000, 0.73 (95% CI: 0.66 to 0.78) and additive EuroSCORE, 0.73 (95% CI: 0.67-0.78). Chi-square = 0.10, p (x2) = 0.74.

544

Original Article


Arq Bras Cardiol. 2014; 102(6):539-548

We could attribute this difference to the higher prevalence of rheumatic fever as the pathogenesis of valve disease, in addition to Chagas disease, which require complex surgical procedures and often more than one surgery.

Grinberg et al22, in 2011, prompted by the Brazilian reality, which is different from that of Europe and the United States, proposed that the approach of the patient with valvular disease follow a strategy called “valvulopathy resolution script” (RESOLVA). In this script, which consists of four stages, the application of an international risk score is only one of the elements that assist in decision-making. The score result should be evaluated together with the conceptual benefit of the procedure given by scientific knowledge, with the autonomy of the team and patient in decision-making and discussion of two ethical principles (negligence and malpractice).

On the other hand, Guaragna et al23, in 2010, created a local risk score for patients undergoing valve surgery, eliminating the use of international scores. Advanced age, surgical priority,

female gender, ejection fraction < 45%, concomitant CABG, pulmonary hypertension, NYHA functional class III or IV, creatinine (1.5 to 2.49 and > 2.5 mg/dL or dialysis) were identified as risk predictors.

Similarly, Mejia et al24, in 2013, developed a score based on data from patients undergoing cardiac surgery at a single referral center for cardiac surgery. Patients with indication for valve surgery and CABG were included. The score comprised ten variables: age > 70 years, female gender, valve surgery combined with CABG, acute myocardial infarction < 90 days, reoperation, surgical treatment of the aortic valve, tricuspid valve surgery, creatinine > 2 mg / dL, EF < 30% and events. This local score was compared with the ES and the BP, and its performance was similar to theirs, with good discriminatory power (AUC of 0.79 versus 0.81 and 0.82, respectively).

Although some studies have tested the applicability of the ES in valvular surgery, in a meta-analysis of 12 studies with 26,621 patients, Parolari et al25 observed that this score had low discriminatory power in this type of surgery, as it

Table 5 – Observed and expected mortality in the additive and logistic EuroSCORE in risk groups

ExpectedMortality

Observed Mortality SMR

EuroSCORE N N % N % Estimate LL UL

Additive

0 a 2 303 4 1.3 7 2.3 1.8 0.7 3.7

3 a 5 395 11 2.8 24 6.1 2.1 1.3 3.1

≥ 6 365 42 11.5 51 14.0 1.2 0.9 1.6

Total 1.063 57 5.4 82 7.7 1.4 1.1 1.8

Logistic

≤ 0,02 354 5 1.3 10 2.8 2.1 1.0 3.8

0,021 a 0,05 358 11 3.5 22 6.1 2.0 1.2 3.0

≥ 0,06 351 41 11.8 50 14.2 1.2 0.9 1.6

Total 1063 57 5.4 82 7.7 1.4 1.1 1.8

LL: Lower limit; UL: Upper limit; SMR: Standardized Mortality Rate.

Table 6 – Independent predictors for in-hospital mortality in the sample according to logistic regression

Risk factors Odds ratio(95%CI)

Diabetes mellitus 2.28 (1.34-3.88)

CABG combined with valvular surgeryAge 76-79 yearsPrevious cardiac surgery

2.38 (1.18-4.80)2.49 (1.12-5.54)2.68 (1.40-5.12)

Two or more previous cardiac surgeries 3.34 (1.16-9.63)

Systolic pulmonary artery pressure > 60 mmHg 3.44 (1.60-7.39)

Age > 80 years 3.61 (1.54-8.45)

Active endocarditis 4.38 (1.00-19.17)

Serum creatinine > 2.26 mg/dL 4.71 (1.28-17.34)

CABG: Coronary artery bypass grafting.

545

Original Article


Arq Bras Cardiol. 2014; 102(6):539-548

overestimates mortality. Once again it should be noted that the mortality rate in valvular surgery in these studies was around 4.5%, whereas in our sample it was 8.6% and in the population studied by Guaragna et al23, 11.8%.

Patients with pulmonary hypertension (sPAP > 60 mmHg) - a condition associated with valvular diseases - were more prevalent than in the initial ES population (5.2% versus 2.0%) and had higher risk of in-hospital mortality (OR = 3.44; 95%CI: 1.60 to 7.39). Another limitation of risk scores studied in patients with valvular disease is the fact that specific surgical procedures were not evaluated, e.g., combined aortic and mitral valve surgeries.

Our institution treats patients coming from public health centers, with significant socioeconomic problems, which lead to medication misuse, poor health status and advanced stage of disease at surgery. This may explain in part the higher prevalence of combined CABG and valve surgery procedure with high mortality in our sample (20%), which showed to be an independent risk factor in the multivariate analysis. A study carried out in Spain by Pons et al26 in 1994 showed that postoperative in-hospital mortality in public hospitals was higher than that of private hospitals (11.7% versus 6.7%, respectively).

Another aspect to consider is that the higher difference between the expected and observed mortalities occurred in patients at moderate risk, both in the additive BP and ES. One might consider that score applicability was compromised in our sample by evaluating different populations, both due to the profile of patients, as well as the socioeconomic aspects and the higher prevalence of valvular surgery.

It is important to consider that the small number of patients who used intra-aortic balloon (IAB) preoperatively also indicates the possible under-utilization of this resource in more severe patients, contributing to increased mortality. Another relevant fact is that the logistic regression showed DM as an independent risk factor for mortality in our sample, and that this diagnosis was not scored in ES. However, the new ES model that is being proposed has included this variable27.

The present study has limitations that should be considered. At the time of the manuscript writing , EuroSCORE I was still used, which has been currently updated and replaced by EuroSCORE II27. Mortality in 30 days or long-term survival was not assessed. Another limitation is that our sample consisted of a very heterogeneous population, which may have allowed biases in the results. Moreover, our study has limitations inherent to retrospective studies, with 14% of missing data. However, some risk models described in the literature were developed from pre-existing databases2,28-30. Some variables evaluated subjectively, such as the degree of COPD,

degree of neurological damage and heart failure, had their definitions adapted similarly to what was performed in other studies17,31.

When comparing the Society of Thoracic Surgeons risk score (STS) with the ES in an institution in Sweden, the definition of recent acute myocardial infarction was 21 days and not 90 days, as proposed by ES31. Even with this adjustment, the ES had significantly better discriminatory power than the STS (AUC 0.84 versus 0.71). In the initial Parsonnet study, COPD was considered a risk factor that was difficult to obtain and was removed from the score model, even though it was associated with postoperative mortality1. For the same reason, emergency surgery and chronic heart failure were removed from the ES5.

ConclusionsThe use of the Berstein Parsonnet 2000 and EuroSCORE

underestimated the intra-hospital mortality, showing them to be inappropriate in the preoperative evaluation of patients undergoing cardiac surgery at our institution. Independent predictors of in-hospital mortality in our sample were: age, serum creatinine > 2.26 mg/dL, active endocarditis, pulmonary artery pressure > 60 mmHg, one or more previous heart surgeries, CABG combined with valve surgery and diabetes mellitus. Our study reinforces the need for the development of local scores, based on the reality of the populations, for better risk assessment in cardiac surgery.

Author contributionsConception and design of the research, Analysis and

interpretation of the data, Statistical analysis and Writing of the manuscript: Garofallo SB, Portal VL; Acquisition of data: Garofallo SB, Machado DP, Rodrigues CG, Bordim Jr. O; Critical revision of the manuscript for intellectual content: Garofallo SB, Kalil RAK, Portal VL.

Potential Conflict of InterestNo potential conflict of interest relevant to this article was

reported.


Study AssociationThis article is part of the thesis of master submitted by Silvia

Bueno Garofallo, from Instituto de Cardiologia/Fundação Universitária de Cardiologia.

546

Original Article


Arq Bras Cardiol. 2014; 102(6):539-548

1. Parsonnet V, Dean D, Bernstein AD. A method of uniform stratification of risk for evaluating the results of surgery in acquired adult heart disease. Circulation. 1989;79(6 Pt 2):I3-12.

2. Bernstein AD, Parsonnet V. Bedside estimation of risk as an aid for decision-making in cardiac surgery. Ann Thorac Surg. 2000;69(3):823-8.

3. Michel P, Roques F, Nashef SA; EuroSCORE Project Group. Logistic or additive EuroSCORE for high-risk patients? Eur J Cardiothorac Surg. 2003;23(5):684-7.

4. Roques F, Nashef SA, Michel P; EuroSCORE Project Group. Regional differences in surgical heart valve disease in Europe: comparison between northern and southern subsets of the EuroSCORE database. J Heart Valve Dis. 2003;12(1):1-6.

5. Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg. 1999;16(1):9-13.

6. Ribeiro AL, Gagliardi SP, Nogueira JL, Silveira LM, Colosimo EA, Lopes do Nascimento CA. Mortality related to cardiac surgery in Brazil, 2000-2003. J Thorac Cardiovasc Surg. 2006;131(4):907-9.

7. Piegas LS, Bittar OJ, Haddad N. Myocardial revascularization surgery (MRS): results from national health system (SUS). Arq Bras Cardiol. 2009;93(5):555-60.

8. Shibata MC, Flather MD, de Arenaza DP, Wang D, O’Shea JC. Potential impact of socioeconomic differences on clinical outcomes in international clinical trials. Am Heart J. 2001;141(6):1019-24.

9. Peterson ED, Coombs LP, DeLong ER, Haan CK, Ferguson TB. Procedural volume as a marker of quality for CABG surgery. JAMA. 2004;291(2):195-201.

10. Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176(6):532-55.

11. Roques F, Michel P, Goldstone AR, Nashef SA. The logistic EuroSCORE. Eur Heart J. 2003;24(9):881-2.

12. Nashef SA, Roques F, Michel P, Cortina J, Faichney A, Gams E, et al. Coronary surgery in Europe: comparison of the national subsets of the European system for cardiac operative risk evaluation database. Eur J Cardiothorac Surg. 2000;17(4):396-9.

13. Moons KG, Donders RA, Stijnen T, Harrell Jr FE. Using the outcome for imputation of missing predictor values was preferred. J Clin Epidemiol. 2006;59(10):1092-101.

14. Donders AR, van der Heijden GJ, Stijnen T, Moons KG. Review: a gentle introduction to imputation of missing values. J Clin Epidemiol. 2006;59(10):1087-91.

15. Breslow NE, Day NE. Statistical methods in cancer research. Lyon: International Agency for Research on Cancer; 1987.

16. Gogbashian A, Sedrakyan A, Treasure T. EuroSCORE: a systematic review of international performance. Eur J Cardiothorac Surg. 2004;25(5):695-700.

17. Yap CH, Reid C, Yii M, Rowland MA, Mohajeri M, Skillington PD, et al. Validation of the EuroSCORE model in Australia. Eur J Cardiothorac Surg. 2006;29(4):441-6.

18. Gummert JF, Funkat A, Osswald B, Beckmann A, Schiller W, Krian A, et al. EuroSCORE overestimates the risk of cardiac surgery: results from the national registry of the German Society of Thoracic and Cardiovascular Surgery. Clin Res Cardiol. 2009;98(6):363-9.

19. Berman M, Stamler A, Sahar G, Georghiou GP, Sharoni E, Brauner R, et al. Validation of the 2000 Bernstein-Parsonnet score versus the EuroSCORE as a prognostic tool in cardiac surgery. Ann Thorac Surg. 2006;81(2):537-40.

20. Syed AU, Fawzy H, Farag A, Nemlander A. Predictive value of EuroSCORE and Parsonnet scoring in Saudi population. Heart Lung Circ. 2004;13(4):384-8.

21. Birkmeyer JD, Siewers AE, Finlayson EV, Stukel TA, Lucas FL, Batista I, et al. Hospital volume and surgical mortality in the United States. N Engl J Med. 2002;346(15):1128-37.

22. Grinberg M, Tarasoutchi F, Sampaio RO. Roteiro para resolução de valvopatia (Resolva). Arq Bras Cardiol. 2011;97(4):e86-90.

23. Guaragna JC, Bodanese LC, Bueno FL, Goldani MA. Proposta de escore de risco pré-operatório para pacientes candidatos à cirurgia cardiaca valvar. Arq Bras Cardiol. 2010;94(4):541-48.

24. Mejia AO, Lisboa LB, Puig LB, Moreira LF, Dallan LA, Pomerantzeff PM, et al. InsCor: um método simples e acurado para avaliação do risco em cirurgia cardiaca. Arq Bras Cardiol. 2013;100(3):246-54.

25. Parolari A, Pesce LL, Trezzi M, Cavallotti L, Kassem S, Loardi C, et al. EuroSCORE performance in valve surgery: a meta-analysis. Ann Thorac Surg. 2010;89(3):787-93, 793.e1-2.

26. Pons J, Moreno V, Borras J, Espinas J, Almazan C, Granados A. Open heart surgery in public and private practice. J Health Serv Res Policy. 1999;4(2):73-8.

27. Nashef SA, Roques F, Sharples LD, Nilsson J, Smith C, Goldstone AR, et al. EuroSCORE II. Eur J Cardiothorac Surg. 2012;41(4):734-44.

28. Kuduvalli M, Grayson AD, Au J, Grotte G, Bridgewater B, Fabri BM. A multi-centre additive and logistic risk model for in-hospital mortality following aortic valve replacement. Eur J Cardiothorac Surg. 2007;31(4):607-13.

29. Ambler G, Omar RZ, Royston P, Kinsman R, Keogh BE, Taylor KM. Generic, simple risk stratification model for heart valve surgery. Circulation. 2005;112(2):224-31.

30. Magovern JA, Sakert T, Magovern GJ, Benckart DH, Burkholder JA, Liebler GA, et al. A model that predicts morbidity and mortality after coronary artery bypass graft surgery. J Am Coll Cardiol. 1996;28(5):1147-53.

31. Nilsson J, Algotsson L, Hoglund P, Luhrs C, Brandt J. Early mortality in coronary bypass surgery: the EuroSCORE versus The Society of Thoracic Surgeons risk algorithm. Ann Thorac Surg. 2004;77(4):1235-9.

References

547

Original Article


Arq Bras Cardiol. 2014; 102(6):539-548 548

Original Article

Infarct Size as Predictor of Systolic Functional Recovery after Myocardial InfarctionMarcos F. Minicucci, Elaine Farah, Daniéliso R. Fusco, Ana Lúcia Cogni, Paula S. Azevedo, Katashi Okoshi, Silméia G. Zanati, Beatriz B. Matsubara, Sergio A. R. Paiva, Leonardo A. M. ZornoffFaculdade de Medicina de Botucatu, Universidade Estadual Paulista "Júlio de Mesquita Filho", Botucatu, SP – Brazil

Mailing Address: Leonardo Antônio Mamede Zornoff •Faculdade de Medicina de Botucatu, Departamento de Clinica Médica, Rubião Jr. Postal Code 18618-970, Botucatu, SP – BrazilE-mail: [email protected]; [email protected] received August 13, 2013; revised manuscript November 19, 2013, accepted December 27, 2013.

DOI: 10.5935/abc.20140051

Abstract

Background: The effects of modern therapy on functional recovery after acute myocardial infarction (AMI) are unknown.

Objectives: To evaluate the predictors of systolic functional recovery after anterior AMI in patients undergoing modern therapy (reperfusion, aggressive platelet antiaggregant therapy, angiotensin-converting enzyme inhibitors and beta-blockers).

Methods: A total of 94 consecutive patients with AMI with ST-segment elevation were enrolled. Echocardiograms were performed during the in-hospital phase and after 6 months. Systolic dysfunction was defined as ejection fraction value < 50%.

Results: In the initial echocardiogram, 64% of patients had systolic dysfunction. Patients with ventricular dysfunction had greater infarct size, assessed by the measurement of total and isoenzyme MB creatine kinase enzymes, than patients without dysfunction. Additionally, 24.5% of patients that initially had systolic dysfunction showed recovery within 6 months after AMI. Patients who recovered ventricular function had smaller infarct sizes, but larger values of ejection fraction and E-wave deceleration time than patients without recovery. At the multivariate analysis, it can be observed that infarct size was the only independent predictor of functional recovery after 6 months of AMI when adjusted for age, gender, ejection fraction and E-wave deceleration time.

Conclusion: In spite of aggressive treatment, systolic ventricular dysfunction remains a frequent event after the anterior myocardial infarction. Additionally, 25% of patients show functional recovery. Finally, infarct size was the only significant predictor of functional recovery after six months of acute myocardial infarction. (Arq Bras Cardiol. 2014; 102(6):549-556)

Keywords: Myocardial Infarction; Heart Failure; Ventricular Dysfunction; Recovery of Function.

IntroductionMany factors determine the outcome of patients after an

Acute Myocardial Infarction (AMI)1,2. Among these prognostic factors, heart failure is highlighted due to left ventricular dysfunction. In fact, cardiac dysfunction after AMI increases the risk of death by three to four-fold3.

Epidemiological studies report that signs and symptoms of heart failure after infarction occur in approximately 25% of patients with AMI. Additionally, large clinical trials report that approximately 40% of AMI cases are accompanied by left ventricular systolic dysfunction, suggesting that functional deterioration is a common event after AMI4.

An important aspect to be considered, however, is that a considerable percentage of patients with systolic dysfunction

in the acute phase of myocardial infarction show functional recovery over time. However, the current prevalence and risk factors for prediction of functional recovery are not completely understood.

Thus, this study aimed to evaluate the prevalence and predictors of systolic functional recovery after AMI in patients undergoing modern therapy after anterior myocardial infarction.

Methods

DesignThe present was a prospective, observational study carried out

in the coronary care unit of our institution. Consecutive patients of both genders that had the first episode of anterior AMI from December 2008 to December 2010 were included in the study.

The diagnosis of anterior AMI was established by a history of chest pain lasting more than 20 minutes and the presence of ST-segment elevation in at least two contiguous precordial leads (V1-V4) or the presence of new complete left bundle branch block at the electrocardiogram. Exclusion criteria were: congenital heart disease, significant primary valve disease, atrial fibrillation, inadequate

549

Original Article

Minicucci et al.Functional recovery after myocardial infarction

Arq Bras Cardiol. 2014; 102(6):549-556

condition for the completion of first echocardiogram during hospitalization, inadequate echocardiographic window, cancer, autoimmune disease, chronic renal failure (creatinine clearance ≤ 30 mL/min), liver failure and chronic immunosuppressive therapy.

The study protocol was approved by the Ethics Committee of our institution and patients were enrolled after signing the free and informed consent form. During hospitalization, patients were evaluated daily and submitted to the first echocardiogram; the time of follow-up after hospital discharge was 6 months and at 6 months, patients underwent clinical reassessment and a new echocardiogram.

Clinical variables Data related to the clinical profile of patients were

obtained from patient history and physical examination on admission. Blood samples were obtained according to the routine of the Coronary Care Unit. Electrolytes, renal function and blood count were measured on admission and measurement of blood glucose and lipids was performed on samples obtained after a 12-hour fast. The levels of total (CPK) and isoenzyme MB creatine phosphokinase (CK-MB) were assessed at admission and every 6 hours until levels started to decrease. Two measurements of troponin I were performed (on admission and 90 minutes after patient arrival).

Clinical variables were obtained: age, gender, ethnicity, symptoms at admission, duration of chest pain (between the onset of pain and the first assessment in the emergency room), prior coronary revascularization, heart rate, systemic blood pressure and signs of pulmonary and systemic congestion5-8.

The following cardiovascular risk factors were investigated: systemic arterial hypertension (SAH), Diabetes Mellitus (DM), dyslipidemia, smoking, obesity and family history of coronary artery disease5-8.

Patients that reported a previous diagnosis of SAH and that had at least one measurement of systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg, or routinely used antihypertensive drugs were considered hypertensive. Patients that reported a previous diagnosis of DM and were receiving regular treatment, or patients that had two fasting glucose levels ≥ 126 mg/dL or a casual plasma glucose ≥ 200 mg/dL associated with classic symptoms of DM were considered as diabetics. Dyslipidemia was considered in patients on regular use of lipid-lowering medication or the presence of serum Low Density Lipoprotein levels (LDL-C) ≥ 160 mg/dL and/or serum levels of high density lipoprotein (HDL-c) ≤ 40 mg/dL (men) or ≤ 50 mg/dL (women) and/or serum triglycerides ≥ 150 mg/dL.

Patients that smoked daily, regardless of the number of cigarettes, were considered smokers. Patients with first-degree relatives with premature coronary artery disease (men < 55 years and women < 65 years) were considered as having a positive family history for CAD. Finally, obesity was diagnosed by the presence of Body Mass Index (BMI) ≥ 30 kg/m2 and central obesity by the presence of waist circumference > 102 cm for men and > 88 cm for women. Weight and height were

measured on a Welmy Brazil scale, with a maximum capacity of 200 kg and fixed stadiometer. The waist circumference was measured with an inelastic tape in the mid-distance between the iliac crest and the last rib.

Weight, height and waist circumference were measured in the morning, after fasting, 48 hours after admission with patients wearing the standard hospital gown5-8.

Regarding the treatment of AMI, reperfusion strategy and the following drugs prescribed during the in-hospital phase were evaluated: acetylsalicylic acid (ASA), Clopidogrel, heparin (unfractionated or low-molecular weight), Glycoprotein IIb/IIIa receptor inhibitor (IGP IIb/IIIa) inhibitors, angiotensin-converting enzyme inhibitors (ACEI), beta-blockers, calcium-channel blockers, nitrates, intravenous positive inotropic agents, diuretics, digitalis, statins, spironolactone and warfarin5-8.

The post-AMI clinical complications that occurred in the in-hospital phase were defined as follows: post-AMI ischemia as the occurrence of chest pain during appropriate drug therapy and/or acute ischemic alterations in the electrocardiogram (ECG) after the second day of evolution after AMI; arrhythmia with occurrence of sustained ventricular tachycardia or ventricular fibrillation; heart failure as clinical or radiological pulmonary congestion that required intravenous diuretic treatment, presence of hypotension as SBP < 90 mmHg for a period > 30 minutes in euvolemic patients with no signs of tissue hypoperfusion; cardiogenic shock, as SBP < 90 mmHg for a period > 30 min and signs of peripheral hypoperfusion (cold extremities, oliguria, sweating, pallor, restlessness or drowsiness) associated with pulmonary congestion and pericarditis, as occurrences of characteristic chest discomfort and associated with pericardial friction or the presence of diffuse ST-segment elevation on the electrocardiogram5-8.

Echocardiographic assessment Morphological and functional evaluation of the left ventricle

(LV) was performed by echocardiography. The examinations were performed by three echocardiographists blinded to patients' clinical characteristics and treatment. Echocardiograms were performed during the in-hospital phase and 6 months after the AMI by the same examiner. In our service, the interobserver variability is < 5% for one-dimensional measurements and < 10% for two-dimensional measurements and Doppler-derived time variables; intraobserver variability is <5% for all variables.

Examinations were performed in a Philips HDI-5000 equipment according to standard technique9. Systolic dysfunction was defined as ejection fraction < 50% assessed by Simpson's method10. Recovery of left ventricular systolic function was defined as an increase in LV ejection fraction > 50% in those patients with dysfunction detected between the first and second echocardiograms.

Statistical analysis Continuous variables are shown as mean and standard

deviation or median and 25% and 75% percentiles in case of non-normal distribution. Proportional variables were analyzed by chi-square test or the Fisher exact test for comparison between groups. Continuous variables were tested for

550

Original Article


Arq Bras Cardiol. 2014; 102(6):549-556

normality; continuous variables with normal distribution were compared by Student's t test, while non-normal continuous variables were compared using the Mann-Whitney test.

Existing associations between the variables and functional recovery after AMI were analyzed by multivariate logistic regression. The occurrence of functional recovery was included as the dependent variable. Variables that showed statistically significant differences in the univariate analysis, plus age and gender, were included as independent variables. The ROC (Receiver Operating Characteristic) curve was used to determine the best infarct size cutoff. The SigmaStat statistical package for Windows 3.5 (Systat Software Inc. - San Jose, CA – USA) was used or statistical analysis. The level of significance was set at 5% for all tests.

ResultsDuring the observation period, 94 patients with anterior AMI

were evaluated. However, eight patients died before the second echocardiogram and three patients were lost to follow-up. Thus, our final sample consisted of 83 patients. Of these, 73% were males, mean age of 58 ± 12 years.

In the initial echocardiogram, 64% of the patients had systolic dysfunction. As expected, patients with ventricular dysfunction had larger infarct sizes, assessed by CPK and CPK-MB enzymes, than patients without dysfunction (Table 1). No differences were found for the other analyzed variables.

Regarding baseline echocardiographic data, patients with ventricular dysfunction had higher LV diameters, associated with lower ejection fractions. There were no other differences between patients with or without dysfunction (Table 2).

Regarding functional recovery, 24.5% of patients with initial systolic dysfunction showed recovery within 6 months after AMI. Patients that recovered ventricular function had smaller infarct sizes than patients without recovery. There were no differences in relation to other clinical variables (Table 3).

Regarding the echocardiographic data, patients that had functional recovery showed higher EDT and ejection fraction than those without recovery. No differences were found for other variables (Table 4).

Multivariate analysis showed that infarct size was the only independent predictor of functional recovery 6 months after AMI, when adjusted for age, gender, ejection fraction, and EDT (Table 5). The ROC curve was used to determine the best cutoff for infarct size as assessed by the MB isoform, which determines LV function recovery, with the following result for the area under the curve: 0.814; 95% confidence interval (95% CI): 0.698 to 0.929, p <0.001, with a cutoff of 521U/L (Figure 1).

DiscussionThis study aimed to evaluate the prevalence and

predictors of systolic functional recovery after AMI in patients

Table 1 – Clinical, demographic and treatment data of 83 patients with anterior-wall acute myocardial infarction

VariablesVentricular dysfunction

p valueYes(n = 53)

No(n = 30)

Age (years) 57.9 ± 11.7 59.2 ± 13.1 0.632

Male, % (n) 75.5 (40) 70.0 (21) 0.777

SAH, % (n) 50.9 (27) 73.3 (22) 0.078

DM, % (n) 24.5 (13) 33.3 (10) 0.545

Dyslipidemia, % (n) 75.5 (40) 80.0 (24) 0.842

BMI (kg/m2) 26.9 (23.6-28.9) 28.9 (24.8-32.0) 0.116

WC (cm) 94.1 ± 9.8 98.1 ± 12.6 0.113

CPK (U/L) 4421 (1.453-7.658) 1.491 (683-4.116) 0.018

CPK-MB (U/L) 445.0 (180.8-734.5) 178.5 (111.0-324.0) 0.002

Primary angio, % (n) 69.8 (37) 66.7 (20) 0.960

Reperfusion, % (n) 84.9 (45) 86.7 (26) 1.000

ASA, % (n) 100 (53) 100 (30) -

Clopidogrel, % (n) 100 (53) 100 (30) -

ARB, % (n) 1.9 (1) 6.7 (2) 0.295

ACEI, % (n) 92.5 (49) 93.3 (28) 1.000

Beta-blocker, % (n) 94.3 (50) 100 (30) 0.550

Spironolactone, % (n) 22.6 (12) 13.3 (4) 0.386

SAH: systemic arterial hypertension; DM: diabetes mellitus; BMI: body mass index; WC: waist circumference; CPK: creatine phosphokinase; CPK-MB: creatine phosphokinase-MB fraction; ASA: acetylsalicylic acid; ARB: angiotensin-II receptor blocker; ACEI: angiotensin-converting enzyme inhibitor. Data expressed as mean ± SD or median (including 25th and 75th percentiles).

551

Original Article


Arq Bras Cardiol. 2014; 102(6):549-556

Table 2 – Echocardiographic data of 83 patients with anterior-wall acute myocardial infarction

VariablesVentricular dysfunction

p valueYes(n = 53)

No(n = 30)

LA (mm) 41.2 ± 4.6 40.9 ± 4.8 0.776

LVEDD (mm) 51.2 ± 5.6 48.7 ± 4.2 0.037

LVESD (mm) 35.7 ± 5.4 31.0 ± 4.0 < 0.001

PW (mm) 10.5 ± 1.4 10.9 ± 1.8 0.309

E/A 0.76 (0.64-0.92) 0.79 (0.71-0.88) 0.624

IVRT (ms) 116 (100-124) 114 (104-128) 0.943

EDT (ms) 215.3 ± 64.5 228.8 ± 60.1 0.360

HR (bpm) 76.4 ± 13.5 74.9 ± 13.4 0.621

EF 0.41 ± 0.05 0.58 ± 0.05 < 0.001

LA: left atrium; LVEDD: left ventricular-end diastolic diameter; LVESD: left ventricular-end systolic diameter; PW: left ventricular posterior wall thickness; IVRT: isovolumetric relaxation time; EDT: E-wave deceleration time; HR: heart rate; EF: ejection fraction. Data expressed as mean ± SD or median (including 25th and 75th percentiles).

Table 3 – Clinical, demographic and treatment data of patients with ventricular dysfunction

VariablesFunctional recovery

p valueYes(n = 13)

No(n = 40)

Age (years) 63.4 ± 12.3 56.2 ± 11.1 0.061

Male, % (n) 69.2 (9) 77.5 (31) 0.712

SAH, % (n) 38.5 (5) 55.0 (22) 0.473

DM, % (n) 15.4 (2) 27.5 (11) 0.480

Dyslipidemia, % (n) 84.6 (11) 72.5 (29) 0.480

BMI (kg/m2) 25.7 ± 3.5 26.8 ± 3.7 0.356

WC (cm) 92.4 ± 9.9 94.6 ± 9.8 0.483

CPK (U/L) 1.351 (841-4.167) 5.587 (2.125-8.269) 0.002

CPK-MB (U/L) 168 (80-273) 579 (254-807) < 0.001

Primary angio, % (n) 69.2 (9) 70.0 (28) 1.000

Reperfusion, % (n) 76.9 (10) 87.5 (35) 0.389

ASA, % (n) 100 (13) 100 (40) -

Clopidogrel, % (n) 100 (13) 100 (40) -

ARB, % (n) 7.7 (1) 0 (0) 0.245

ACEI, % (n) 84.6 (11) 95.0 (38) 0.249

Beta-blocker, % (n) 92.3 (12) 95 (38) 1.000

Spironolactone, % (n) 7.7 (1) 27.5 (11) 0.147

SAH: systemic arterial hypertension; DM: diabetes mellitus; BMI: body mass index; WC: waist circumference; CPK: creatine phosphokinase; CPK-MB: creatine phosphokinase-MB fraction; ASA: acetylsalicylic acid; ARB: angiotensin-II receptor blocker; ACEI: angiotensin-converting enzyme inhibitor. Data expressed as mean ± SD or median (including 25th and 75th percentiles).

undergoing modern therapy after anterior myocardial infarction. Our data suggest that systolic ventricular dysfunction remains a frequent event after AMI, with approximately 25% of patients showing functional recovery. Additionally, infarct size was the only significant predictor of functional recovery 6 months after the acute coronary event.

The first information from our study to be considered is that systolic dysfunction was a common event. In fact, approximately 65% of patients had ventricular dysfunction. Therefore, some factors are worth mentioning.

Firstly, we observed that our patients received the recommended treatment for patients with AMI11. Thus, more

552

Original Article


Arq Bras Cardiol. 2014; 102(6):549-556

Table 4 – Initial echocardiographic data of patients with ventricular dysfunction

VariablesFunctional recovery

p valueYes(n = 13)

No(n = 40)

AE (mm) 39.9 ± 3.0 41.6 ± 5.0 0.239LVEDD (mm) 50.8 ± 3.5 51.4 ± 6.2 0.737LVESD (mm) 34.7 ± 3.9 36.0 ± 5.8 0.467PW (mm) 10.0 (10.0-11.0) 10.7 (9.4-11.4) 0.827E/A 0.75 (0.64-0.86) 0.77 (0.62-0.93) 0.844IVRT (ms) 120 (109-126) 116 (98-125) 0.443EDT (ms) 250.9 ± 77.6 203.5 ± 55.7 0.020HR (bpm) 70.8 ± 12.0 78.2 ± 13.6 0.097EF 0.44 ± 0.06 0.40 ± 0.05 0.006

LA: left atrium; LVEDD: left ventricular-end diastolic diameter; LVESD: left ventricular-end systolic diameter; PW: left ventricular posterior wall thickness; IVRT: isovolumetric relaxation time; EDT: E-wave deceleration time; HR: heart rate; EF: ejection fraction. Data expressed as mean ± SD or median (including 25th and 75th percentiles).

Table 5 – Logistic regression for predicting left ventricular function recovery 6 months after AMI

Patient characteristics Odds Ratio 95%CI p valueGender 1.719 0.236-12.509 0.593Age (years) 1.062 0.986-1.144 0.114EF (%) 1.137 0.895-1.445 0.294EDT (ms) 1.002 0.982-1.002 0.845CPK-MB (U/L) 0.995 0.990-0.999 0.015

95%CI: 95% confidence interval; EF: ejection fraction; EDT: E-wave deceleration time; CPK-MB: creatine phosphokinase-MB fraction.

Figure 1 – ROC curve of the infarct size measured by peak CK-MB isoform, which determines left ventricular function recovery. Area under the curve: 0.814, 95% confidence interval: 0.698 to 0.929, p value < 0.001, and cutoff of 521U / L.

1 - Specificity

0.0 0.2 0.4 0.6 0.8 1.0

Se��it

i�ity

0.0

0.2

0.4

0.6

0.8

1.0

Sens

itivit

y

1 - Specificity

553

Original Article


Arq Bras Cardiol. 2014; 102(6):549-556

than 85% of patients were submitted to reperfusion therapy - most by primary angioplasty - 100% of patients received dual antiplatelet therapy and over 90% received beta-blockers and ACE inhibitors. However, we concluded that in most of our patients, this aggressive treatment was not capable of preventing the occurrence of ventricular dysfunction.

Another fact to be considered refers to the fact that the definition of systolic dysfunction is controversial, with different values of ejection fraction (≤ 35%, <40% or <45%) being considered in clinical trials. Our study determined that only patients with ejection fraction > 50% were considered as having completely normal systolic function, in agreement with a recent guideline10. This might have contributed to the high prevalence of dysfunction in our analysis.

To better understand functional recovery after AMI, one must consider the potential mechanisms of dysfunction after infarction. After the ischemic injury, the main physiopathological mechanisms that explain ventricular dysfunction include: loss of contractile capacity dependent on the affected amount of muscle, hearts affected by other comorbidities, mechanical complications, stunned myocardium and cardiac remodeling process4.

However, of the aforementioned mechanisms, the stunned myocardium is the one that best explains functional recovery over time12,13. Corroborating this hypothesis, we consider that currently, a significant number of patients with AMI are submitted to reperfusion therapy, which increases the likelihood of stunned myocardium and functional recovery14-17. Therefore, our study assumes that the stunned myocardium plays a crucial role in functional recovery after coronary occlusion. However, questions remain about the impact of more contemporary therapy on functional improvement and what the predictors of functional recovery are.

In the most recent study, which assessed patients from the HEART study, more than 50% of patients showed functional improvement after reperfusion and 24% had complete recovery within 2 weeks. It is important to emphasize that in this study, 65% of patients underwent thrombolytic therapy, whereas only 15% were submitted to primary angioplasty18. In our study, more than 65% of patients underwent primary angioplasty. However, our rate of complete functional recovery

was similar to that observed in the HEART study. Thus, one can infer that our more aggressive treatment strategy had little additional impact on functional recovery of patients with AMI.

Finally, our study, in agreement with a previous one18, suggests that infarct size is the only predictor of functional recovery, therefore being superior to functional variables. Additionally, our study suggests that CPK-MB levels < 521U/L, a simple method for assessing infarct size, could be incorporated into clinical practice to predict functional recovery in patients after anterior wall AMI with ST elevation.

ConclusionIn conclusion, our study indicates that, despite aggressive

treatment, systolic ventricular dysfunction remains a frequent event after AMI with ST-segment elevation. Additionally, 25% of patients show functional recovery. Finally, infarct size is the only significant predictor of functional recovery 6 months after the acute coronary event.

Author contributionsConception and design of the research: Zornoff LAM;

Acquisition of data: Fusco DR, Cogni AL, Azevedo PS, Okoshi K, Zanati SG, Paiva SAR, Zornoff LAM; Analysis and interpretation of the data: Fusco DR, Cogni AL, Azevedo PS, Okoshi K, Zanati SG, Paiva SAR; Obtaining financing: Zornoff LAM; Statistical analysis: Zornoff LAM; Writing of the manuscript: Zornoff LAM; Critical revision of the manuscript for intellectual content: Azevedo PS, Paiva SAR, Zornoff LAM.


was reported. Sources of FundingThere were no external funding sources for this study. Study AssociationThis study is not associated with any thesis or dissertation work.

1. Lee KL, Woodlief LH, Topol EJ, Weaver WD, Betriu A, Col J, et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction: results from an international trial of 41.021 patients. GUSTO-I Investigators. Circulation. 1995;91(6):1659-68.

2. Zornoff LA, Paiva SA, Duarte DR, Spadaro J. Ventricular remodeling after myocardial infarction: concepts and clinical implications. Arq Bras Cardiol. 2009;92(2):157-64.

3. Risk stratification and survival after myocardial infarction. N Engl J Med. 1983;309(6):331-6.

4. Minicucci MF, Azevedo PS, Polegato BF, Paiva SA, Zornoff LA. Heart failure after myocardial infarction: clinical implications and treatment. Clin Cardiol. 2011;34(7):410-4.

5. Cogni AL, Farah E, Minicucci MF, Azevedo PS, Okoshi K, Matsubara BB, et al. Waist circumference, but not body mass index, is a predictor of ventricular remodeling. Nutrition. 2013;29(1):122-6.

6. Farah E, Cogni AL, Minicucci MF, Azevedo PS, Okoshi K, Matsubara BB, et al. Prevalence and predictors of ventricular remodeling after anterior myocardial infarction in the era of modern medical therapy. Med Sci Monit. 2012;18(5):CR276-81.

7. Azevedo PS, Cogni AL, Farah E, Minicucci MF, Okoshi K, Matsubara BB, et al. Predictors of right ventricle dysfunction after anterior myocardial infarction. Can J Cardiol. 2012;28(4):438-42.

8. Farah E, Fusco DR, Okumoto PR, Minicucci MF, Azevedo PS, Matsubara BB, et al. Impact of ventricular geometric pattern on cardiac remodeling after myocardial infarction. Arq Bras Cardiol. 2013;100(6):518-23.

References

554

Original Article


Arq Bras Cardiol. 2014; 102(6):549-556

9. Lang RM, Bierig M, Devereaux RB, Flachskampf FA, Foster E, Pellikka PA, et al. 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.

10. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, et al; ESC Committee for Practice Guidelines. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33(14):1787-847. Erratum in: Eur Heart J. 2013 Jan;34(2):158.

11. O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):529-55.

12. Christian TF, Behrenbeck T, Pellikka PA, Huber KC, Chesebro JH, Gibbons RJ. Mismatch of left ventricular function and infarct size demonstrated by technetium-99m isonitrile imaging after reperfusion

therapy for acute myocardial infarction: identification of myocardial stunning and hyperkinesia. J Am Coll Cardiol. 1990;16(7):1632-8.

13. Bolli R. Myocardial ‘stunning’ in man. Circulation. 1992;86(6):1671-91.

14. Ito H, Tomooka T, Sakai N, Higashino Y, Fujii K, Katoh O, et al. Time course of functional improvement in stunned myocardium in risk area in patients with reperfused anterior infarction. Circulation. 1993;87(2):355-62.

15. Serruys PW, Simoons ML, Suryapranata H, Vermeer F, Wijns W, van den Brand M, et al. Preservation of global and regional left ventricular function after early thrombolysis in acute myocardial infarction. J Am Coll Cardiol. 1986;7(4):729-42.

16. Sheehan FH, Doerr R, Schmidt WG, Bolson EL, Uebis R, von Essen R, et al. Early recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction: an important determinant of survival. J Am Coll Cardiol. 1988;12(2):289-300.

17. Schofer J, Lins M, Mathey DG, Sheehan FH. Time course of left ventricular function and coronary patency after saruplase vs streptokinase in acute myocardial infarction. The PRIMI Trial Study Group. Eur Heart J. 1993;14(7):958-63.

18. Solomon SD, Glynn RJ, Greaves S, Ajani U, Rouleau JL, Menapace F, et al. Recovery of ventricular function after myocardial infarction in the reperfusion era: the healing and early afterload reducing therapy study. Ann Intern Med. 2001;134(6):451-8.

555

Original Article


Arq Bras Cardiol. 2014; 102(6):549-556 556

Original Article

Mortality by Heart Failure and Ischemic Heart Disease in Brazil from 1996 to 2011Eduardo Nagib Gaui1, Gláucia Maria Moraes de Oliveira1, Carlos Henrique Klein2

Universidade Federal do Rio de Janeiro1; Escola Nacional de Saúde Pública Sérgio Arouca da Fundação Oswaldo Cruz2, Rio de Janeiro, RJ - Brazil

Mailing Address: Eduardo Nagib Gaui •Rua Real Grandeza, 139, sala 903, Botafogo. Postal Code 22281-033, Rio de Janeiro, RJ – BrazilE-mail: [email protected] Manuscript received December 06, 2013; revised manuscript February 09, 2014; accepted April 16, 2014.

DOI: 10.5935/abc.20140072

AbstractBackground: Circulatory system diseases are the first cause of death in Brazil.

Objective: To analyze the evolution of mortality caused by heart failure, by ischemic heart diseases and by ill-defined causes, as well as their possible relations, in Brazil and in the geoeconomic regions of the country (North, Northeast, Center-West, South and Southeast), from 1996 to 2011.

Methods: Data were obtained from DATASUS and death declaration records with codes I20 and I24 for acute ischemic diseases, I25 for chronic ischemic diseases, and I50 for heart failure, and codes in chapter XIII for ill-defined causes, according to geoeconomic regions of Brazil, from 1996 to 2011.

Results: Mortality rates due to heart failure declined in Brazil and its regions, except for the North and the Northeast. Mortality rates due to acute ischemic heart diseases increased in the North and Northeast regions, especially from 2005 on; they remained stable in the Center-West region; and decreased in the South and in the Southeast. Mortality due to chronic ischemic heart diseases decreased in Brazil and in the Center-West, South and Southeast regions, and had little variation in the North and in the Northeast. The highest mortality rates due to ill-defined causes occurred in the Northeast until 2005.

Conclusions: Mortality due to heart failure is decreasing in Brazil and in all of its geoeconomic regions. The temporal evolution of mortality caused by ischemic heart diseases was similar to that of heart failure. The decreasing number of deaths due to ill-defined causes may represent the improvement in the quality of information about mortality in Brazil. The evolution of acute ischemic heart diseases ranged according to regions, being possibly confused with the differential evolution of ill-defined causes. (Arq Bras Cardiol. 2014; 102(6):557-565)

Keywords: Heart Failure / mortality; Myocardial Ischemia / mortality; Epidemiology; Brazil.

IntroductionCirculatory System Diseases (CSD) are the main causes of

death in Brazil. In 2011, CSDs were responsible for 28.6% of the 1,170,498 deaths that occurred in the country. Ischemic Heart Diseases (IHD) and Heart Failure (HF) were responsible for 39.1% of the deaths caused by CSD1. In the past decades, especially in the South and Southeast regions, it has been possible to observe decreasing mortality due to CSD in Brazil2. The same behavior has been observed in Europe3. In 2008, in the United States, 32.8% of all 2,471,984 deaths were caused by CSD, whose mortality rate was of 244.8 per 100,000 inhabitants; however, from 1998 to 2008, these rates presented a 30.6% decrease4.

Mortality rates due to IHD in Brazil have presented decreasing tendency in the past decades. The analysis of a temporal series from 1981 to 2001 showed declining mortality rates due to IHD in the South and Southeast regions, being stable in the Center-West region and increasing in the Northeast5. Mortality rates due to IHD in Brazil and in the metropolitan region of São Paulo (RMSP), in a more recent period (from 1990 to 2009), revealed the maintenance of the progressive decline observed earlier, in all of the analyzed age groups and in both sexes. The decreasing mortality rates caused by IHD were higher in RMSP than in Brazil as a whole2. This behavior was also observed in CSD, including the IHD, in the States of Rio de Janeiro, São Paulo and Rio Grande do Sul, where mortality rates declined from 1980 to 20066.

National data about the behavior of mortality due to HF are scarce. Most publications about the magnitude of HF as a cause of death in Brazil derive from cohort studies7,8 and from analyses concerning hospital mortality9. According to death records in Rio de Janeiro, São Paulo and Rio Grande do Sul, specific mortality rates due to HF in these States, both for men and women, declined in all ages, except for individuals aged 80 years old or more10.

557

Original Article

Gaui et al.Mortality by HF and IHD in Brazil

Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0

Goldacre et al11, in England, analyzed the population of Oxford, from 1979 to 2003, and concluded that mortality rates due to HF and IHD had similar declining rates11. Murdoch et al12 studied HF in Scotland, from 1979 to 1992, and besides the observation of declining mortality, they also noticed that 30 to 40% of deaths attributed to IHD may have been related to HF, which demonstrates the correlation of these two conditions.

Mortality statistics is the most useful way to analyze the health status of a population and to plan the necessary health promotion actions. The quality of information about causes of death, therefore, is essential. One of the indicators used to assess the quality of these data is the proportion of deaths attributed to Ill-Defined Causes (IDC). This indicator not only qualifies information, but it also points to the proper analysis of mortality. In Brazil, in 2003, IDC was codified as a basic cause of death in 13.3% of all deaths, and the highest percentages were in the North and the Northeast regions, with 25.9% and 21.1%, respectively13.

The objective of this study was to analyze the evolution of mortality caused by HF, IHD and IDC and their possible relations, in Brazil and according to its geographic regions, from 1996 to 2011.

MethodsThe death declarations (DD) records of each Brazilian

state, from 1996 to 2011, were obtained from the website of the Unified Health System Information System (DATASUS) (http://tabnet.datasus.gov.br/cgi/sim/dados/cid10_indice.htm#dados, which was accessed in November, 2013. Afterwards, records from DDs of the five regions in Brazil were obtained by the sum of States that compose each region.

Populations in census years were also obtained in the DATASUS website (http://www2.datasus.gov.br/DATASUS/index.php?area=0206&VObj=http://tabnet.datasus.gov.br/cgi/deftohtm.exe?ibge/cnv/pop, which was accessed in November, 2013, by age groups (younger than 1 year old, from 1 to 4 years old, from 5 to 9, from 10 to 14, from 15 to 19, and after that, with 10 year intervals, up to the age of 80). However, the census estimates provided by the Brazilian Institute of Geography and Statistics (IBGE) were not used due to the change of methods adopted after 2007, which caused abrupt and unlikely inflexions in all age groups. These inflexions could lead to disturbances in mortality rate estimates. The populations of inter-census years were obtained by the estimates in each age group, with the arithmetic progression method14.

Computed DD records used the mortality classification of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (CID-10), in order to codify causes of death. We selected records with codes I20 to I24 for acute IHD, I25 for chronic IHD, I50 for HF and codes in chapter XIII for IDC. The considered cause of death was the one codified as the basic cause of death, according to rules in CID-1015.

The annual mortality rates in Brazil and its geographic regions were calculated, caused by acute IHD, chronic IHD,

HF and IDC, per 100 thousand inhabitants, with crude and direct standardized methods, according to the referred age groups. The pattern was the age distribution of the Brazilian population in 2000. These rates were distributed in graphs of annual temporal series for each selected group of causes of death in Brazil and its regions.

The statistical software Stata, version 1216, was used to calculate mortality rates and to elaborate the graphs.

ResultsCrude mortality rates caused by HF declined in Brazil

and in almost all of its regions, except for the Northeast (Figure 1A). When we observe the standardized rates, this decline is more evident, even in the Northeast, and differences between geographic regions decrease, especially in more recent periods (Figure 1B). In Brazil, the reduced mortality from the first to the last year of the temporal series was of 32.1% in crude rates, and 54.0% in standardized rates (Table 1). The highest crude mortality rates due to HF for the whole period were observed in the South and in the Southeast. However, after considering age distribution, the Center-West presented the highest rates for almost the entire period, and the South was very close (Figure 1B).

In Figure 1C, referring to crude mortality rates caused by acute IHD, it is possible to observe an increasing tendency in the North, Northeast and Center-West regions. From the first to the last year of the series, there was an increase of 77.6% in the North; 124.0% in the Northeast; and 52.4% in the Center-West (Tables 2 to 4).There was a discrete declining tendency in the South and in the Southeast. In the composition of regions, rates in Brazil presented increasing tendency from 2005 on.

Mortality rates due to acute IHD, when standardized by age, as demonstrated in Figure 1D, increased in the North and Northeast regions, especially from 2005 on. These rates remained stable in the Center-West region. In the South and Southeast regions, rates declined throughout the period. In Brazil, these rates declined throughout the period – and a bit less from 2005 on. From the first to the last year, there was a decrease of 34.2% in the Southeast region (Table 5), 35.2% in the South (Table 6), while, in Brazil, it was of 17.3% (Table 1).

Crude mortality rates due to chronic IHD, which can be seen in Figure 1E, were stable in Brazil and in most regions, except for the Northeast, which had a 3.0 rate per 100 thousand inhabitants in 1996, and 4.8 in 2011, which represented a 60% increase (Table 3).

In Figure F, it is possible to observe that standardized mortality rates due to chronic IHD decreased in Brazil and in the Center-West, South and Southeast regions, with little variation in the North and Northeast regions. In Brazil, in 1996, the rate was of 9.5 per 100 thousand inhabitants, while, in 2011, it was 32.6% lower (Table 1).

Mortality rates due to IDC, presented in Figure 1G, declined in all regions. In the North and Northeast regions, this decline was more present from 2004 on. In these regions, from the first to the last year of the period, declines were of 71 and 44%, respectively.

558

Original Article



Table 1 – Crude and standardized mortality* per 100 thousand, due to selected causes - Brazil, 1996-2011

YearHeart failure Acute ischemic

heart diseasesChronic ischemic

heart diseases Ill-defined causes

Crude Standardized Crude Standardized Crude Standardized Crude Standardized

1996 21.2 23.5 38.5 42.0 8.5 9.5 87.5 85.1

1997 19.7 21.2 38.0 40.5 8.0 8.6 83.1 88.3

1998 19.5 20.5 38.3 39.9 8.1 8.5 86.3 89.7

1999 17.7 18.2 37.6 38.4 8.4 8.6 85.1 86.7

2000 16.6 16.6 37.8 37.8 8.4 8.4 79.9 79.9

2001 16.0 15.5 37.9 36.8 8.3 8.0 79.0 76.9

2002 15.7 14.7 38.5 36.3 8.3 7.8 77.1 73.2

2003 15.4 14.1 39.0 35.9 8.2 7.5 75.8 70.2

2004 15.5 13.7 40.2 36.0 8.5 7.6 71.2 64.4

2005 14.7 12.7 39.0 34.1 8.1 7.0 57.9 51.2

2006 15.3 12.9 41.2 35.2 8.5 7.2 46.9 40.7

2007 15.2 12.4 41.9 35.0 8.2 6.8 43.5 37.0

2008 14.8 11.8 43.0 35.1 8.3 6.7 42.4 35.5

2009 14.5 11.3 43.0 34.4 8.1 6.4 41.9 34.4

2010 14.4 11.0 44.2 34.6 8.2 6.3 41.7 33.6

2011 14.4 10.8 45.2 34.7 8.5 6.4 40.6 32.1

Source of data: deaths – SUS Information System (DATASUS); population – Brazilian Institute of Geography and Statistics (count of 1996, census of 2000 and 2010 and linear estimation). * Direct standardization method, according to age groups in DATASUS - Standard: Brazil, year 2000.

Table 2 – Crude and standardized mortality* per 100 thousand, due to selected causes – North region, 1996-2011





1996 10.5 17.4 13.4 21.7 1.7 2.9 82.6 122.6

1997 9.9 16.0 13.7 21.6 1.8 2.9 84.0 121.4

1998 10.1 16.0 13.8 21.4 1.5 2.4 87.5 124.7

1999 10.1 15.8 14.5 22.3 1.4 2.2 88.7 124.7

2000 9.2 13.9 14.5 22.0 1.2 1.9 88.3 121.3

2001 10.1 14.8 15.0 21.8 1.5 2.3 87.1 118.3

2002 8.8 12.6 14.9 21.1 1.2 1.7 80.6 106.5

2003 9.1 12.6 16.0 22.1 1.5 2.1 81.1 105.3

2004 8.3 11.3 17.1 23.1 1.5 2.1 80.0 102.4

2005 8.9 11.8 17.0 22.4 1.4 1.9 67.5 85.1

2006 8.5 11.1 18.1 23.3 1.8 2.4 57.2 70.8

2007 9.0 11.5 20.2 25.5 1.5 1.9 48.4 59.0

2008 8.5 10.6 21.3 26.4 1.7 2.2 50.8 61.1

2009 8.2 10.1 22.7 27.6 1.9 2.3 50.9 60.5

2010 8.4 10.2 22.8 27.4 1.8 2.2 48.7 57.1

2011 9.0 10.8 23.8 28.2 1.9 2.3 46.2 53.7


559

Original Article



Table 3 – Crude and standardized mortality* per 100 thousand, due to selected causes – Northeast Region, 1996-2011





1996 13.6 14.5 19.2 21.3 3.0 3.2 148.1 154.7

1997 13.4 14.0 20.5 22.3 2.9 3.0 142.1 145.7

1998 13.8 14.2 21.3 22.7 3.0 3.1 144.8 145.7

1999 13.2 13.2 20.7 21.6 3.1 3.2 143.1 141.6

2000 13.2 13.0 22.0 22.6 3.5 3.4 135.8 132.4

2001 13.2 12.7 24.2 24.2 3.6 3.4 135.8 129.6

2002 13.7 12.8 25.4 24.8 3.6 3.4 136.6 127.7

2003 13.6 12.4 26.4 25.2 3.4 3.1 132.7 121.4

2004 13.8 12.3 28.3 26.4 3.6 3.2 121.7 109.3

2005 13.0 11.3 30.4 27.7 3.4 3.0 86.8 76.4

2006 14.4 12.2 34.9 31.1 4.3 3.7 47.6 41.3

2007 14.1 11.7 37.3 32.5 4.2 3.5 41.1 35.0

2008 13.5 11.0 39.2 33.2 4.5 3.8 41.5 34.8

2009 13.0 10.4 39.7 33.5 4.2 3.4 41.3 34.3

2010 12.2 9.5 40.2 33.1 4.7 3.8 41.8 34.0

2011 12.8 9.8 43.0 34.7 4.8 3.8 43.4 34.6


Table 4 – Crude and standardized mortality* per 100 thousand, due to selected causes – Center-West region 1996-2011





1996 19.4 29.0 24.6 34.3 5.8 8.9 50.9 70.5

1997 20.8 29.8 24.5 33.2 5.5 8.1 50.3 67.0

1998 19.4 27.2 25.9 33.8 5.2 7.4 51.1 66.3

1999 16.8 23.1 25.6 32.8 5.2 7.1 48.4 60.0

2000 15.7 20.7 27.6 34.3 5.7 7.6 39.6 49.2

2001 15.6 19.8 28.4 34.1 5.9 7.4 36.8 44.1

2002 15.8 19.3 30.2 35.1 6.3 7.7 31.7 37.1

2003 15.3 17.9 30.8 34.7 6.7 7.8 27.2 30.7

2004 15.2 17.3 32.4 35.3 7.8 8.7 28.8 31.7

2005 13.8 15.2 30.9 32.9 6.9 7.5 24.9 26.7

2006 14.7 15.8 32.2 33.2 7.3 7.6 23.5 24.6

2007 13.8 14.5 32.1 32.4 6.6 6.8 20.7 21.1

2008 14.6 14.9 32.9 32.5 7.6 7.6 20.2 20.3

2009 14.1 14.1 34.3 33.1 6.1 6.0 19.2 18.9

2010 13.6 13.3 36.7 34.7 5.9 5.7 20.7 19.9

2011 12.2 11.7 37.5 34.7 6.1 5.7 23.0 21.9


560

Original Article



Table 5 – Crude and standardized mortality* per 100 thousand, due to selected causes – Southeast Region, 1996-2011





1996 26.3 27.5 53.1 54.0 11.8 12.5 64.3 65.9

1997 23.6 24.0 51.5 51.0 11.2 11.4 61.7 61.8

1998 22.8 22.5 50.6 48.9 10.9 10.8 66.2 64.8

1999 20.5 19.7 49.5 46.8 11.6 11.1 66.6 63.9

2000 18.5 17.4 48.5 44.9 11.4 10.7 62.5 58.8

2001 17.4 15.7 48.3 43.3 11.2 10.1 61.3 56.0

2002 16.6 14.5 48.6 42.3 11.1 9.6 58.1 51.7

2003 16.5 13.9 49.2 41.6 11.2 9.4 57.3 49.7

2004 16.6 13.6 49.8 41.0 11.4 9.3 54.6 46.0

2005 16.0 12.7 47.0 37.6 11.0 8.7 50.5 41.7

2006 16.3 12.6 49.0 38.3 11.1 8.6 52.3 42.3

2007 16.1 12.1 48.5 37.0 10.6 8.0 51.0 40.3

2008 15.6 11.4 49.5 36.9 10.7 7.9 48.7 37.9

2009 15.6 11.1 48.8 35.7 10.4 7.5 47.4 36.0

2010 16.0 11.1 50.9 36.4 10.4 7.3 47.3 35.3

2011 15.6 10.7 50.7 35.5 11.1 7.6 44.3 32.5


Table 6 – Crude and standardized mortality* per 100 thousand, due to selected causes – South Region, 1996-2011





1996 27.2 29.7 51.9 53.9 14.0 15.1 56.8 60.5

1997 24.6 25.9 50.9 51.4 13.0 13.5 46.6 48.2

1998 25.6 26.2 53.5 52.6 14.4 14.6 48.4 49.0

1999 22.7 22.6 52.9 50.8 14.3 14.1 42.8 42.3

2000 21.9 21.2 53.7 50.4 14.0 13.4 38.3 37.1

2001 20.5 19.2 50.6 46.0 13.5 12.5 37.5 35.1

2002 20.4 18.4 50.5 44.5 14.1 12.6 38.3 34.7

2003 19.4 16.9 49.9 42.6 13.3 11.5 40.7 35.9

2004 19.3 16.3 51.2 42.5 13.7 11.4 38.7 33.1

2005 18.1 14.8 48.3 39.0 13.0 10.5 35.2 29.4

2006 18.3 14.5 48.0 37.8 13.3 10.4 35.6 29.0

2007 18.7 14.4 48.9 37.5 13.9 10.6 35.0 27.9

2008 18.4 13.7 48.8 36.6 12.7 9.4 32.3 25.2

2009 18.0 13.1 48.3 35.3 13.6 9.9 33.3 25.3

2010 18.3 13.0 48.6 34.7 13.4 9.5 31.9 23.8

2011 18.4 12.8 50.0 34.9 13.0 9.0 30.4 22.3


561

Original Article



Figure 1 - (A) Crude mortality due to heart failure (HF), per 100 thousand, in Brazilian regions, from 1996 to 2011. (B) Standardized mortality due to heart failure, per 100 thousand, in Brazilian regions, from 1996 to 2011 – direct standardization method, according to age groups of DATASUS (pattern: Brazil 2000). (C) Crude mortality due to acute ischemic heart diseases (IHD), per 100 thousand, in Brazilian regions, from 1996 to 2011. (D) Standardized mortality due to acute ischemic heart diseases, per 100 thousand, in Brazilian regions, from 1996 to 2011 – direct standardization method, according to age groups of DATASUS (pattern: Brazil 2000). (E) Crude mortality due to chronic ischemic heart diseases, per 100 thousand, in Brazilian regions, from 1996 to 2011. (F) Standardized mortality due to chronic ischemic heart diseases, per 100 thousand, in Brazilian regions, from 1996 to 2011 – direct standardization method, according to age groups of DATASUS (pattern: Brazil 2000). (G) Crude mortality due to ill-defined causes, per 100 thousand, in Brazilian regions, from 1996 to 2011. (H) Standardized mortality due to ill-defined causes, per 100 thousand, in Brazilian regions, from 1996 to 2011 – direct standardization method, according to age groups of DATASUS (pattern: Brazil 2000).

30

30

25

25

Morta

lity/10

0 tho

usan

d20

20

15

15

10

10

1996 1998 2000 2002

Mortality caused by HF (/100 thousand) in Brazilian regions

North

North

North

North North

North

North

NorthNortheast

Northeast

Northeast

Northeast Northeast

Northeast

Northeast

NortheastSouth

South

South

South South

South

South

SouthBrazil

Brazil

Brazil

Brazil Brazil

Brazil

Brazil

BrazilSoutheast

Southeast

Southeast

Southeast Southeast

Southeast

Southeast

SoutheastCenter-West

Center-West

Center-West

Center-West Center-West

Center-West

Center-West

Center-West

2004ano

2006 2008 2010

Morta

lity/10

0 tho

usan

d20 30

30 40

40 50

50 60

10 20

1996 1998 2000 2002

Mortality caused by acute IHD (/100 thousand) in Brazilian regions

2004ano

2006 2008 2010Mo

rtality

/100 t

hous

and

1996 1998 2000 2002

Mortality caused by acute IHD (/100 thousand) in Brazilian regions

2004ano

2006 2008 2010

Standardization by age


1996 1998 2000 2002 2004 2006 2008 2010ano

Morta

lity/10

0 tho

usan

d

Mortality caused by HF (/100 thousand) in Brazilian regions

15

15

Morta

lity/10

0 tho

usan

d10

10

5 5

0 0

1996 1998 2000 2002 2004ano

2006 2008 2010

Mortality caused by chronic IHD (/100 thousand) in Brazilian regions

150

150

100

100

Morta

lity/10

0 tho

usan

d50 50

0 0

1996 1998 2000 2002 2004ano

2006 2008 2010

Mortality caused by ill-defined causes IHD (/100 thousand) in Brazilian regions


Morta

lity/10

0 tho

usan

d

1996 1998 2000 2002 2004ano

2006 2008 2010

Mortality caused by ill-defined causes IHD (/100 thousand) in Brazilian region


Morta

lity/10

0 tho

usan

d

1996 1998 2000 2002 2004ano

2006 2008 2010

Mortality caused by chronic IHD (/100 thousand) in Brazilian regions

A B

C D

E F

G H

562

Original Article



The highest mortality rates due to IDC, both crude and standardized, occurred in the Northeast until 2004. From that point on, the North and the Southeast regions were leaders in these rates (Figures 1G and 1H).

DiscussionMortality rates due to HF declined in Brazil throughout the

analyzed period. Despite the different rates between geographic regions in the country, all of them presented declining numbers (Figures 1A and 1B). The highest crude rates occurred in the South and the Southeast regions, probably because the population in these States is older in relation to the others. That would also explain the decreasing differences observed between regions and the increasing rates in the Center-West region, when these are standardized by age. In the last years of the analyzed series (2011), the differences between standardized rates, which revealed the effect of differences in age, were the lowest in the period.

The decreasing mortality rates due to HF in this study were in accordance with other results published in the few studies about the subject that were conducted in Brazil10, 17,18, in which mortality due to HF was also analyzed in DDs.

The same has been observed in other countries. Najafi et al19 analyzed mortality due to HF in Australia, from 1997 to 2003, and found declining rates. They conclude that this fact is related to changes in diagnosis or in the codification of causes of death, thus reflecting changes in HF epidemiology19. In the United States, mortality due to HF was also declining. From 1993 to 2003, the number of deaths due to HF increased 20.5%, and even so, the mortality rate decreased in 2.0%20.

Laribi et al21 studied mortality rates due to HF in seven countries of Europe, and concluded that these numbers reduced 40% in the period between 1987 and 2008. The mean age of death due to HF increased, both for men and women. The authors still consider that these results may be related to improvements in the treatment in the past 20 years21.

Fonarow et al22 assessed the impact of the main treatments tested in several clinical trials, which are recommended by the guidelines of the two largest American societies of cardiology, would have on mortality by HF. Six recommended therapeutic prescriptions estimated that the potential increase of lives saved a year could range between 9.6 and 31.5%22.

In Holland, even with the increasing prescription of drugs to treat HF, no improvement was observed in the prognosis of the first year after hospital discharge after hospitalizations due to HF, when comparing the periods of 1998-2002 and 2003-2007. However, the prescription of renin-angiotensin-Aldosterone system inhibitors and beta blockers was not higher than 60% in the second period of this series23.

In this study, mortality caused by acute IHD presented different behaviors, depending on the region. As with HF, the highest rates were concentrated in the South and in the Southeast, and the lowest ones, in the North and in the Northeast (Figures 1C and 1D). Rates in the South and in the Southeast presented decreasing tendency, especially when standardized; the ones in the North and Northeast region tended to increase throughout the period, mostly after 2005. In 2011, the mortality strength of acute IHD, despite the

differences of age structure, was practically the same in all regions, except for the North. However, since the growth tendency remained in this region, soon enough the mortality strength of acute IHD in the North will reach the same levels of the other regions.

It is possible to speculate that the decreasing differences are not explained by changes in patterns of deaths caused by acute IHD between the regions, but instead, by changes in the way DDs are filled out. And that is because, in the middle of the studied period, around 2005, the number of ill-defined or undetermined causes of death in DDs decreased notably in the North and Northeast regions. Therefore, it is possible that most declarations that previously contained ill-defined causes changed into acute IHD as the cause of death (Figures 1C, 1D, 1G e 1H).

As in acute IHD, the South and the Southeast regions also had the highest mortality rates due to chronic IHD, and the North and the Northeast, the lowest ones (Figures 1E e 1F). However, in this group of IHD, the decrease observed in strength mortality in the South and in the Southeast, after the exclusion of age differences, can make regional differences minimum in the future.

Mortality rates due to acute and chronic IHD in Brazil, as a whole, are a weighed composition of regional rates. Therefore, if the latter are heterogeneous, the global rate of the country does not sum up what happened in any part of the territory throughout the period (Figures 1C e 1D e Table 1).

The regional differences concerning the mortality behavior due to IHD in Brazil reported here have been published before. A temporal series5 from 1981 to 2001 demonstrated the declining mortality rates due to IHD in the South and Southeast regions, being stable in the Center-West region and higher in the Northeast region. The authors, Souza et al5 related the declining tendency of circulatory diseases to the probable improvement in the control of risk factors, such as smoking, dyslipidemias, diabetes and systemic arterial hypertension. The control of these factors, the primary and secondary prevention, would be more adequate in more developed regions, and it could explain the observed regional differences5.

In a series from 1990 to 2009, it was also possible to observe declining mortality rates due to IHD. The mortality due to this condition in RMSP was higher than the numbers in Brazil, however, it also presented a stronger decreasing tendency than in the country, both among men (36.2% vs. 23,5%) and women (44.5% vs. 29.5%)2.

Soares et al6 analyzed mortality due to all causes and caused by CSD, IHD and Cerebrovascular Diseases (CVDs), from 1980 to 2006, in Rio de Janeiro, in Rio Grande do Sul and in São Paulo, and found decreasing mortality rates due to all groups of causes. The decreasing mortality due to all causes was mostly attributed to the relevant decline in mortality by CSD. The authors speculated that these results may be a result of the slower decrease of mortality due to infectious diseases and of the improved life conditions of the population6.

In a more recent publication, these authors reinforce the validity of this hypothesis by studying the evolution of socioeconomic indicators and cardiovascular mortality in the

563

Original Article



same three Brazilian states. There was a strong correlation between the decreasing child mortality rates, the increasing Gross Domestic Product (GPD) per capita and the increasing schooling with the reduced mortality due to CSD, IHD and CVDs in adults of the studied series of 1980 to 200824.

One of the indicators of quality concerning the death records is the proportion of causes of death codified as ill-defined ones13. In Brazil, the proportion of deaths due to IDC was around 20%, from 1970 to 1986. After 1987, this proportion declined progressively, reaching 15%, in 2996, and being still unsatisfactory in 2003, with 13.3%13.

A study about death reclassification due to IDC in DDs, in the late 1990s, in the State of Rio de Janeiro, found that the CSD were the most likely causes of death. Proportional mortality due to CSD was higher in reclassified ill-defined causes, according to information obtained by the Authorization Forms for Hospital Admission25. Therefore, it is possible that the increasing levels of death rates due to acute IHD, which is an important component of CSD, has occurred together with the decline in death rates due to IDC, observed in the North and in the Northeast.

In this study, we observed a decreasing tendency in mortality caused by IDC in all of the Brazilian regions, however, with major variation (Figures 1G and 1H). The Northeast and North regions, in this order, presented the highest rates throughout the years, however, the decline of these rates was more present after 2004, especially in the Northeast. However, the Southeast region, which presents more economic progress and has the largest population contingent, still has high levels of mortality caused by IDC in the last years of the series.

We can speculate that the temporal evolution of mortality rates due to chronic IHD and HF are similar in the South, Southeast, and Center-West regions. At the same time, in the North and the Northeast, deaths caused by IDC and acute and chronic IHD and HF competed, which made it difficult to assess the evolution of each of the groups of defined causes and their relations. Therefore, it was possible to observe in the region of Oxford, in England, from 1979 to 200311, that the decreasing mortality rates due to acute and chronic IHD was not followed by the increasing mortality due to HF – this could only be observed in the South of Brazil in the studied period. In the other regions, flows and high levels of deaths due to IDC disturb the analysis of the combined evolution of IHD and HF.

This main limiting factor for this study was the quality of information about cause of death, which depended on the diagnosis of the causes and the proper filling out of the DD; the use of the basic cause of death to analyze mortality can also be a limiting factor. For some conditions, such as HF, mortality can be underestimated, when we do not use the multiple cause analysis, which contemplates all causes mentioned in the DD10,26,27.

ConclusionMortality caused by heart failure has been declining in Brazil

consistently for all major geoeconomic regions. Mortality due to acute ischemic heart disease declined in the South and the Southeast regions, but remained stable in the Center-West and increased in the North and Northeast regions. The behavior of mortality due to chronic ischemic heart diseases was similar with that of heart failure. The decline observed in deaths due to ill-defined causes may represent an improvement in the quality of information about mortality in Brazil. For the proper planning of public health policies that aim at decreasing the mortality due to circulatory system diseases, the observed regional differences must be considered.

Author contributionsConception and design of the research, Acquisition of

data, Analysis and interpretation of the data, Statistical analysis, Writing of the manuscript and Critical revision of the manuscript for intellectual content: Gaui EN, Oliveira GMM, Klein CH.


was reported.


Study AssociationThis article is part of the thesis of Doctoral submitted

by Eduardo Nagib Gaui, from Universidade Federal do Rio de Janeiro.

1. Ministério da Saúde. Secretaria Executiva. Datasus. Informações de Saúde. Estatisticas vitais. [Acesso em 2013 nov 20] Disponivel em: http://www.datasus.gov.br

2. Mansur AP, Favarato D. Mortalidade por doenças cardiovasculares no Brasil e na Região Metropolitana de São Paulo: atualização 2011. Arq Bras Cardiol. 2012;99(2):755-61.

3. Helis E, Augustincic L, Steiner S, Chen L, Turton P, Fodor JG. Time trends in cardiovascular and all-cause mortality in the “old” and “new” European Union countries. Eur J Cardiovasc Prev Rehabil. 2011;18(3):347-59.

4. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics- 2012 update: a report from American Heart Association. Circulation. 2012;125(1):e2-e220.

5. Souza MF, Alencar AP, Malta DC, Moura L, Mansur AP. Análise de séries temporais da mortalidade por doenças isquemicas do coração e cerebrovasculares, nas cinco regiões do Brasil, no periodo de 1981 a 2001. Arq Bras Cardiol. 2006;87(6):735-40.

6. Soares GP, Brum JD, Oliveira GM, Klein CH, Silva NA. Mortalidade por todas as causas e por doenças cardiovasculares em tres estados do Brasil, 1980 a 2006. Rev Panam Salud Publica. 2010;28(4):258-66.

References

564

Original Article



7. Rassi S, Barreto CP, Porto CC, Pereira CR, Calaça BW, Rassi DC. Sobrevida e fatores prognósticos na insuficiencia cardiaca sistólica com inicio recente dos sintomas. Arq Bras Cardiol. 2005;84(4):309-13.

8. Latado AL, Passos LC, Braga JC, Santos A, Guedes R, Moura SS, et al. Preditores de letalidade hospitalar em pacientes com insuficiencia cardiaca avançada. Arq Bras Cardiol. 2006;87(2):185-92.

9. Albanesi Filho FM. Indicadores de doença cardiovascular no estado do Rio de Janeiro com relevo para a insuficiencia cardiaca. Rev SOCERJ. 2004;17(4):264-9.

10. Gaui EN, Klein CH, Oliveira GM. Mortalidade por insuficiencia cardiaca: análise ampliada e tendencia temporal em tres estados do Brasil. Arq Bras Cardiol. 2010;94(1):55-61.

11. Goldacre MJ, Mant D, Duncan M, Griffith M. Mortality from heart failure in an English population, 1979-2003: study of death certification. J Epidemiol Community Health. 2005;59(9):782-4.

12. Murdoch DR, Love MP, Robb TA, McDonagh TA, Davie AP, Ford I, et al. Importance of heart failure as a cause of death: changing contribution to overall mortality and coronary heart disease mortality in Scotland 1979-1992. Eur Heart J. 1998;19(12):1829-35.

13. Santo AH. Causas mal definidas de morte e óbitos sem assistencia. Rev Assoc Med Bras. 2008;54(1):23-8.

14. Laurenti R, Mello Jorge MH, Lebrão ML, Gotlieb SLD. Estatisticas de Saúde. São Paulo: EPU; 2005.

15. Organização Mundial de Saúde (OMS). Classificação estatistica internacional de doenças e problemas relacionados à saúde. São Paulo: EDUSP; 1997.

16. Stata 8.2 statistics/data analysis, Special Edition. Statacorp 4905 Lakeway Drive College Station, Texas, USA; 2005.

17. Latado AL, Passos LC, Guedes R, Santos AB, Andrade M, Moura S. Tendencia da mortalidade por insuficiencia cardiaca em Salvador, Bahia, Brasil. Arq Bras Cardiol. 2005; 85: 327-32.

18. Gaui EN, Klein CH, Oliveira GM. Mortalidade por insuficiencia cardiaca como causa básica ou contribuinte de óbito em tres estados brasileiros, de 1999 a 2004. Rev SOCERJ. 2008;21(3):129-37.

19. Najafi F, Dobson AJ, Jamrozik K. Is mortality from heart failure increasing in Austrália? An analysis of official data on mortality for 1997-2003. Bull World Health Organ. 2006;84(9):722-8.

20. Thom T, Haase N, Rosamond W, Howard VJ, Rumsfeld J, Manolio T, et al. Heart disease and stroke statistics – 2006 update: a report from American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2006;113(6):e85-159.

21. Laribi S, Aouba A, Nikolaou M, Lassus J, Cohen-Solal A, Plaisance P, et al. Trends in death attributed to heart failure over the past two decades in Europe. Eur J Heart Fail. 2012;14(3):234-9.

22. Fonarow GC, Yancy CW, Hernandez AF, Peterson ED, Spertus JA, Heindenreich PA. Potential impact of optimal implementation of evidence-based heart failure therapies on mortality. Am Heart J. 2011;161(6):1024-30.

23. de Peuter OR, Lip GY, Souverein PC, Klungel OH, de Boer A, Büller HR, et al. Time-trends in treatment and cardiovascular events in patients with heart failure: a pharmacosurveillance study. Eur J Heart Fail. 2011;13(5):489-95.

24. Soares GP, Brum JD, Oliveira GM, Klein CH, Souza e Silva NA. Evolução de indicadores socioeconômicos e da mortalidade cardiovascular em tres estados do Brasil. Arq Bras Cardiol. 2013;100(2):147-56.

25. Teixeira CS, Klein CH, Block KV. Reclassificação dos grupos de causas prováveis de óbitos de causa mal definida, com base nas Autorizações de Internação Hospitalar no Sistema Único de Saúde, Estado do Rio de Janeiro, Brasil. Cad Saúde Pública. 2006;22(6):1315-24.

26. Santo AH. Potencial epidemiológico da utilização das causas múltiplas de morte por meio de suas menções nas declarações de óbito, Brasil, 2003. Rev Panam Salud Publica. 2007;22(3):178-86.

27. Engelfriet PM, Hoogenveen RT, Boshuizen HC, van Baal PH. To die with or from heart failure: a difference that counts. Eur J Heart Fail. 2011;13(4):377-83.

565

Original Article

Femoral versus Radial Access in Primary Angioplasty. Analysis of the ACCEPT RegistryPedro Beraldo de Andrade1, Mônica Vieira Athanazio de Andrade1, Robson Alves Barbosa1, André Labrunie1, Mauro Esteves Hernandes2, Roberto Luiz Marino3, Dalton Bertolim Precoma4, Francisco Carleial Feijó de Sá5, Otávio Berwanger6, Luiz Alberto Piva e Mattos7,8,9

Santa Casa de Misericórdia de Marília1, São Paulo - SP; Santa Casa de Votuporanga2, São Paulo - SP; Hospital Madre Teresa3, Belo Horizonte - MG; Sociedade Hospital Angelina Caron4, Campina Grande do Sul - PR; Hospital do Coração do Cariri5, Barbalha - CE; Instituto de Ensino e Pesquisa do Hospital do Coração6, São Paulo - SP; Sociedade Brasileira de Cardiologia7, São Paulo - SP; Instituto Dante Pazzanese de Cardiologia8, São Paulo - SP; Unidades de Hemodinâmica e Intervenção Cardiovascular Rede D’Or / São Luiz9, São Paulo, SP - Brazil

Mailing Address: Pedro Beraldo de Andrade •Avenida Vicente Ferreira, 828. Postal Code 17515-900, Marilia, SP – BrazilE-mail: [email protected]; [email protected] received November 19, 2013; revised manuscript February 18, 2014; accepted February 20, 2014

DOI: 10.5935/abc.20140063

Abstract

Background: The radial access provides a lower risk of bleeding and vascular complications related to the puncture site in comparison to the femoral access. Recent studies have suggested a reduction in mortality associated with the radial access in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

Objective: To compare the occurrence of adverse cardiovascular ischemic and hemorrhagic events in patients undergoing primary angioplasty according to the type of arterial access route.

Methods: From August 2010 to December 2011, 588 patients undergoing primary percutaneous coronary intervention during acute ST-segment elevation myocardial infarction were assessed; they were recruited from 47 centers participating in the ACCEPT registry. Patients were grouped and compared according to the arterial access used for the procedure.

Results: The mean age was 61.8 years; 75% were males and 24% had diabetes mellitus. There was no difference between groups as regards the procedure success rate, as well as regards the occurrence of death, reinfarction, or stroke at six months of follow-up. Severe bleeding was reported in 1.1% of the sample analyzed, with no statistical difference related to the access used.

Conclusions: The femoral and radial accesses are equally safe and effective for the performance of primary percutaneous coronary intervention. The low rate of cardiovascular events and of hemorrhagic complications reflects the quality of the participating centers and the operators expertise with the use of both techniques. (Arq Bras Cardiol. 2014; 102(6):566-570)

Keywords: Myocardial Infarction; Percutaneous Coronary Interventions; Femoral Artery / surgery; Radial Artery / surgery.

IntroductionThe growing interest for the radial access as a strategy for

the reduction of hemorrhagic complications in percutaneous coronary intervention (PCI) confirms the impact of severe bleeding as a determinant of a poorer prognosis in invasively stratified patients with acute coronary syndrome (ACS)1-3. Bleeding events related to the arterial access are the most frequent among patients undergoing coronary procedures and are independently associated with increased one-year mortality4. Recent reviews of guidelines dedicated to this subject suggest the option of the radial access as preferable

to the femoral access, as long as employed by operators both experienced and familiar with the technique5,6.

Patients with ST-segment elevation acute myocardial infarction (AMI) undergoing primary PCI – commonly treated with aggressive adjunctive antithrombotic drug therapy, comprise the clinical group for which the benefits from the radial technique are more expressive7. However, many of the centers involved in randomized trials comparing the access routes in this scenario are known to adopt the radial technique as the first option in their procedures, thus representing a potential selection bias of these analyses.

The Acute Coronary Syndrome Clinical Practice Registry (ACCEPT) is a nationwide Brazilian case series that aims to provide a panorama of the demographic profile and of the occurrence of severe clinical endpoints in patients with ACS. The objective of the present analysis is to compare the six-month follow-up occurrence of severe adverse cardiovascular ischemic and hemorrhagic events among patients included in this registry and undergoing primary PCI, according to the arterial access used in the procedure.

566

Original Article

Andrade et al.Arterial access in primary angioplasty

Arq Bras Cardiol. 2014; 102(6):566-570

MethodsThe ACCEPT rationale, methodology, organization and

registry committees have already been described elsewhere8,9. In sum, it is a prospective, voluntary, multicenter study conceived and managed by the Brazilian Society of Cardiology (Sociedade Brasileira de Cardiologia – SBC), logistically structured in the first semester of 2010, with patient data collection starting from August 2010. For this purpose, 47 investigation centers were gathered in order to reach the largest possible territorial area representing all the Brazilian federative regions, including public hospital care centers (Single Health System), health maintenance organizations, or private health care centers. These centers were selected using two criteria: by inviting qualified institutions and by actively searching for new centers, using the SBC’s website to offer the opportunity to participate. The inclusion criteria were the presence of a research ethics committee (REC), ability to follow up the patients for up to one year, and presence of patients fitting the clinical scope of this registry.

All centers were given training on the protocol and the electronic system, whether in the classroom or by telephone, supported by the coordination team. Quality control of the study data was measured by different strategies, such as the use of an electronic form dedicated to the collection of clinical variables, central control of the variables collected, attendance monitoring in the five centers with the largest number of patients recruited, and random raffle of 20% of the centers for attendance monitoring. The protocol was approved by the REC of Hospital do Coração de São Paulo and, subsequently, each participating center had its local approval. All patients gave written informed consent to participate, and the clinical study was carried out according to the principles of the current review of the Declaration of Helsinki, the Guidelines of Good Clinical Practices, and Resolution 196/96.

In the present analysis, we assessed patients with ST-segment elevation AMI undergoing primary PCI, grouped according to the arterial access used, whether femoral or radial. The clinical endpoints analyzed were cardiovascular mortality, reinfarction, stroke, and severe bleeding . The occurrence of the clinical endpoints mentioned

was checked after hospital admission and at 180 days. In compliance with the Bleeding Academic Research Consortium (BARC) classification10, severe bleeding was defined as that of type 3, subdivided into (3a) – bleeding plus hemoglobin drop ≥ 3 and < 5 g/dL, or red blood cell transfusion; (3b) – bleeding with hemoglobin drop ≥ 5 g/dL, or cardiac tamponade, or bleeding requiring surgical intervention for control; (3c) – intracranial hemorrhage or subcategories confirmed by autopsy, imaging studies or lumbar puncture, or intraocular bleed compromising vision. Also, type 5 subdivided into (5a) – probable fatal bleeding, and (5b), definite fatal bleeding.

Continuous variables with skewed and normal distribution were described as median and mean ± standard deviation, respectively. Categorical variables were described as absolute and relative frequencies. Proportions were compared between two independent groups using Fisher’s exact test. Means were compared using Student’s t test for independent samples. Medians were compared using the Mann-Whitney test. The SAS 9.3 program (Statistical Analysis System, Cary, NC) was used for the statistical analysis of data. P values are two-tailed and p < 0.05 were considered statistically significant.

This registry is proprietary of SBC, using its own financial resources dedicated to this purpose. The Instituto de Ensino e Pesquisa do Hospital do Coração de São Paulo (IEP/Hcor) was hired to operationalize the performance of this registry, under coordination of SBC.

ResultsWe analyzed 2608 patients enrolled until December

2011, corresponding to phase I of the project; their dedicated electronic file was fully filled up (at admission, 30 and 180 days), and 640 had undergone primary PCI. A total of 8.1% of patients (52 cases) were lost to follow-up at six months, thus the final analysis was restricted to 588 patients, 410 of whom were allocated to the femoral group and 178 to the radial group. Their baseline clinical characteristics and demographics are shown in Table 1.

Table 1 – Baseline clinical characteristics and demographics

Variables Overall(n=588)

Femoral(n=410)

Radial(n=178) p

Age, mean ± standard deviation 61.8 ± 12.3 63.1 ± 12.3 58.9 ± 11.7 < 0.001

Male gender, n (%) 442 (75.2) 300 (73.2) 142 (79.8) 0.097

Female gender, n (%) 146 (24.8) 110 (26.8) 36 (20.2) 0.097

Systemic hypertension, n (%) 395 (67.2) 279 (68.0) 116 (65.2) 0.505

Diabetes mellitus, n (%) 142 (24.1) 97 (23.7) 45 (25.3) 0.676

Dyslipidemia, n (%) 278 (47.3) 203 (49.5) 75 (42.1) 0.106

Obesity, n (%) 187 (31.8) 132 (32.2) 55 (30.9) 0.773

Smoking habit, n (%) 185 (31.5) 115 (28.0) 70 (39.3) 0.009

Previous acute myocardial infarction (%) 121 (20.6) 91 (22.2) 30 (16.9) 0.150

Previous stroke, n (%) 47 (7.9) 27 (6.6) 20 (11.2) 0.068

Chronic kidney failure, n (%) 17 (2.9) 15 (3.7) 2 (1.1) 0.111

567

Original Article


Arq Bras Cardiol. 2014; 102(6):566-570

The mean age was 61.8 years, 75% were males, 24% had diabetes mellitus, and 20% had history of previous AMI. There was a predominance of patients with one-vessel coronary atherosclerotic disease, and the angiographic success rate of primary PCI was achieved in 96.6% of cases by means of broad utilization of coronary endoprostheses, most of which were non-drug eluting stents (Table 2). Double antiplatelet therapy with acetylsalicylic acid and clopidogrel, and anticoagulation therapy with enoxaparin were the most frequently used antithrombotic therapy. Glycoprotein IIb-IIIa inhibitors were prescribed for approximately 20% of procedures, predominantly in the group in which the radial access was used.

The rate of adverse cardiac ischemic events at six months of follow-up was low, and the occurrence of a new AMI was the most frequent complication (Graph 1). Severe bleeding was reported in 1.1% of the sample analyzed, with no statistical difference regarding the access route used.

DiscussionIn 2009, a meta-analysis of 23 randomized studies showed

that the radial access provides a higher than 70% reduction in the prevalence of severe bleeding when compared to the femoral access, especially among patients undergoing primary or rescue PCI, with a potential impact on the reduction of ischemic events11. Two years later, a similar investigation hypothesis was formulated by the Radial versus Femoral Access for Coronary Intervention (RIVAL) study, which compared 7021 patients diagnosed with ACS, of whom 1958 had ST-segment elevation, and found a reduction by 61% in mortality with the use of the radial technique (1.3% versus 3.2%, p = 0.006) in this subgroup of patients12.

Table 2 – Characteristics of the procedures and in-hospital antithrombotic therapy

Variables Overall(n = 588)

Femoral(n = 410)

Radial(n = 178) p

Procedural success rate, n (%) 568 (96.6) 397 (96.8) 171 (96.1) 0.627

Stent implantation, n (%) 562 (98.9) 395 (99.5) 167 (97.7) 0.192

Drug-eluting stent, n (%) 126 (21.4) 116 (28.3) 10 (5.6) < 0.001

Non-drug-eluting stent, n (%) 436 (74.1) 279 (68.0) 157 (88.2) < 0.001

One-vessel, n (%) 275 (48.5) 197 (49.1) 78 (47.0) 0.369

Two-vessel, n (%) 172 (30.3) 131 (32.7) 41 (24.7) 0.030

Multivessel, n (%) 111 (19.6) 69 (17.2) 42 (25.3) 0.066

Acetylsalicylic acid, n (%) 578 (98.3) 405 (98.8) 173 (97.2) 0.179

Clopidogrel, n (%) 561 (95.4) 395 (96.3) 166 (93.3) 0.131

Prasugrel, n (%) 4 (0.7) 4 (100.0) 0 (0.0) 0.320

Ticagrelor, n (%) 7 (1.2) 1 (0.2) 6 (3.4) 0.004

Glycoprotein IIb-IIIa inhibitors, n (%) 105 (17.9) 61 (14.9) 44 (24.7) 0.005

Unfractioned heparin, n (%) 101 (17.2) 83 (20.2) 18 (10.1) 0.003

Enoxaparin, n (%) 377 (64.1) 261 (63.7) 116 (65.2) 0.779

Fondaparinux, n (%) 31 (5.3) 6 (1.5) 25 (14.0) < 0.001

With methodology and statistical power to compare the access routes in the setting of ST-segment elevation ACS, the multicenter study Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome (RIFLE-STEACS) analyzed 1001 patients, and showed a significant clinical benefit with the use of the radial access translated into lower rates of cardiovascular mortality, stroke, AMI, target-vessel revascularization, and severe bleeding (13.6% versus 21.0%, p = 0.003)13. The individual analysis of the components of the primary endpoint showed a significant reduction in cardiovascular mortality and severe bleeding among patients randomized for the radial access, with a considerable reduction of vascular complications in the puncture site as regards the severe bleeding event. A recent meta-analysis involving 12 studies on primary PCI, including the results of the previously mentioned RIVAL and RIFLE-STEACS, and counting with 5055 patients, showed a reduction by 45% in the death risk and by 49% in the risk of severe bleeding with the use of the radial in relation to the femoral technique7.

The role of the learning curve in the proficiency and acquisition of better results with the radial access is recognized14. In the RIVAL study, centers characterized by having a high volume of procedures using the radial access (> 146 transradial PCI/operator/year) benefited from the cross-rate between the techniques, severe vascular complications, and the primary endpoint comprising death, AMI or stroke12. Thus, an important limitation of these publications lies on the concentration of centers having operators experienced in the use of the radial technique, a situation that is evidenced by the low cross-rate between the access routes and the procedure duration in the case series. On the other hand, the improvement of the femoral

568

Original Article


Arq Bras Cardiol. 2014; 102(6):566-570

Graph 1 – Clinical endpoints (%) at six months of follow-up.

technique, by means of the reduction of endovascular device diameter, early removal of the arterial introducer, preference for the femoral puncture technique, sometimes guided by fluoroscopy or ultrasound, and the option for antithrombotic agents with a better safety profile, also translates into a lower incidence of complications. In fact, a Brazilian case series of 205 consecutive patients with AMI undergoing the invasive drug strategy with tenecteplase showed an incidence of only 1.5% of severe vascular hemorrhagic complications after femoral puncture15.

In the ACCEPT registry, the rate of ischemic and hemorrhagic events was low using both access routes, but in agreement with that of other studies published with a similar population12. We can assume that, once national reference centers with a broad experience in the use of interventional techniques are included, the differences in the success and complication rates will be attenuated in the final assessment. However, the registry has limitations. The voluntary inclusion of patients by center, in a non-consecutive fashion, and the non-systematic adjudication of events are restrictions to the unequivocal acceptance of its results.

ConclusionsThe femoral and radial access routes are equally safe

and effective for the performance of primary percutaneous coronary interventions. The low rate of cardiovascular events

and of hemorrhagic complications reflects the quality of the centers participating in the ACCEPT registry and the operators expertise with the use of both techniques.

Author contributionsConception and design of the research and Analysis

and interpretation of the data and Critical revision of the manuscript for intellectual content: Andrade PB, Berwanger O, Piva e Mattos LA; Acquisition of data: Andrade PB, Andrade MVA, Barbosa RA, Labrunie A, Hernandes ME, Marino RL, Precoma DB, Sá FCF, Berwanger O, Piva e Mattos LA; Statistical analysis and Obtaining financing: Berwanger O; Writing of the manuscript: Andrade PB.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Sources of Funding

There were no external funding sources for this study.

Study Association

This study is not associated with any thesis or dissertation work.

569

Original Article


Arq Bras Cardiol. 2014; 102(6):566-570

1. Pocock SJ, Mehran R, Clayton TC, Nikolsky E, Parise H, Fahy M, et al. Prognostic modeling of individual patient risk and mortality impact of ischemic and hemorrhagic complications: assessment from the Acute Catheterization and Urgent Intervention Triage Strategy trial. Circulation. 2010;121(1):43-51.

2. Doyle BJ, Rihal CS, Gastineau DA, Holmes, Jr DR. Bleeding, blood transfusion, and increased mortality after percutaneous coronary intervention: implications for contemporary practice. J Am Coll Cardiol Interv. 2009;22(22):2019-27.

3. de Andrade PB, Tebet MA, Maia da Silva FS, Athanazio de Andrade MV, Labrunie A, Piva e Mattos LA. Major bleeding in acute coronary syndromes. J Invasive Cardiol. 2011;23(11):485-90.

4. Ndrepepa G, Neumann FJ, Richardt G, Schulz S, Tölg R, Stoyanov KM, et al. Prognostic value of access and non–access sites bleeding after percutaneous coronary intervention. Circ Cardiovasc Interv. 2013;6(4):354-61.

5. Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. The Task Force on the management of St-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur Heart J. 2012;33(20):2569-619.

6. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58(24):e44-122. Erratum in: Circulation. 2012;125(8):e412.

7. Karrowni W, Vyas A, Giacomino B, Schweizer M, Blevins A, Girotra S, et al. Radial versus femoral access for primary percutaneous interventions in ST-segment elevation myocardial infarction patients. JACC Cardiovasc Interv. 2013;6(8):814-23.

8. Mattos LA. Registro Brasileiro da Prática Clinica nas Sindromes Coronarianas Agudas da Sociedade Brasileira de Cardiologia. Arq Bras Cardiol. 2011;97(2):94-9.

9. Piva e Mattos LA, Berwanger O, Santos ES, Reis HJL, Romano ER, Petriz JLF, et al. Desfechos clinicos aos 30 dias do Registro Brasileiro das Sindromes Coronárias Agudas (ACCEPT). Arq Bras Cardiol. 2013;100(1):6-13.

10. Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123(23):2736-47.

11. Jolly SS, Amlani S, Hamon M, Yusuf S, Mehta SR. Radial versus femoral access for coronary angiography or intervention and the impact on major bleeding and ischemic events: a systematic review and meta-analysis of randomized trials. Am Heart J. 2009;157(1):132-40.

12. Jolly SS, Yusuf S, Cairns J, Niemelä K, Xavier D, Widimsky P, et al. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial. Lancet. 2011;377(9775):1409-20.

13. Romagnoli E, Biondi-Zoccai G, Sciahbasi A, Politi L, Rigattieri S, Pendenza G, et al. Radial versus femoral randomized investigation in ST-elevation acute coronary syndrome: the RIFLE-STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) study. J Am Coll Cardiol. 2012;60(24):2481-9.

14. Rao SV, Tremmel JA, Gilchrist IC, Shah PB, Gulati R, Shroff AR, et al. Best practices for transradial angiography and intervention: a consensus statement from the society for cardiovascular angiography and intervention’s transradial working group. Catheter Cardiovasc Interv. 2013; 83(2):228-36.

15. Caluza AC, Barbosa AH, Gonçalves I, Oliveira CA, Matos LN, Zeefried C, et al. Rede de infarto com supradesnivelamento de ST: sistematização em 205 casos diminui eventos clinicos na rede pública. Arq Bras Cardiol. 2012;99(5):1040-8.

References

570

Original Article

Blood Pressure Control in Hypertensive Patients in the “Hiperdia Program”: A Territory-Based StudyClarita Silva de Souza1, Airton Tetelbom Stein2, Gisele Alsina Nader Bastos2, Lucia Campos Pellanda1,2

Programa de Pós-Graduação em Ciências da Saúde: Cardiologia - Instituto de Cardiologia/Fundação Universitária de Cardiologia1; Universidade Federal de Ciências da Saúde de Porto Alegre – UFCSPA2, Porto Alegre, RS - Brasil

Mailing Address: Lucia Campos Pellanda •Av. Princesa Isabel, 370, Santana, Postal Code 90.620-000, Porto Alegre, RS - BrazilE-mail: [email protected]; [email protected] received September 03, 2013; revised manuscript received January 31, 2014; accepted February 07, 2014.

DOI: 10.5935/abc.20140081

Abstract

Background: Systemic hypertension is highly prevalent and an important risk factor for cardiovascular events. Blood pressure control in hypertensive patients enrolled in the Hiperdia Program, a program of the Single Health System for the follow-up and monitoring of hypertensive patients, is still far below the desired level.

Objective: To describe the epidemiological profile and to assess blood pressure control of patients enrolled in Hiperdia, in the city of Novo Hamburgo (State of Rio Grande do Sul, Brazil).

Methods: Cross-sectional study with a stratified cluster random sample, including 383 adults enrolled in the Hiperdia Program of the 15 Basic Health Units of the city of Porto Alegre, conducted between 2010 and 2011. Controlled blood pressure was defined as ≤140 mmHg × 90 mmHg. The hypertensive patients were interviewed and their blood pressure was measured using a calibrated aneroid device. Prevalence ratios (PR) with 95% confidence interval, Wald’s χ2 test, and simple and multiple Poisson regression were used in the statistical analysis.

Results: The mean age was 63 ± 10 years, and most of the patients were females belonging to social class C, with a low level of education, a sedentary lifestyle, and family history positive for systemic hypertension. Diabetes mellitus (DM) was observed in 31%; adherence to the antihypertensive treatment in 54.3%; and 33.7% had their blood pressure controlled. DM was strongly associated with inadequate BP control, with only 15.7% of the diabetics showing BP considered as controlled.

Conclusion: Even for hypertensive patients enrolled in the Hiperdia Program, BP control is not satisfactorily reached or sustained. Diabetic hypertensive patients show the most inappropriate BP control. (Arq Bras Cardiol. 2014; 102(6):571-578)

Keywords: Hypertension / complications; Risk factors; Hypertension / epidemiology; Government Programs; Epidemiological Monitoring; Medication Adherence.

IntroductionChronic non-communicable diseases (CNCDs) represent

one of the major health challenges for the global development in the coming decades1. Among them, systemic hypertension is an important risk factor for cardiovascular diseases and is present in 69% of patients with a first myocardial infarction, in 77% of patients with a first stroke, in 74% of patients with chronic heart failure, and in 60% of patients with peripheral artery disease2.

Blood pressure control in hypertensive patients is closely related to adherence to the treatment prescribed.

Medication non-adherence is a major concern for health care professionals and stakeholders, so that studies are required to improve adherence to antihypertensive treatments, especially in hypertensive patients at a high cardiovascular risk. In these patients, control of complications may significantly reduce mortality for these diseases, as well as the costs of treating these complications3. Additionally, an inadequate blood pressure control may increase the risk of hypertensive crises with the need for hospitalization4. Several factors may be related to adherence, including the patients’ characteristics, quality of the doctor-patient relationship, severity of disease, access to health care, and specific factors related to the drug prescription5.

Thus, the objective of this study is to describe the epidemiological profile of and to evaluate blood pressure control in patients enrolled in the Hiperdia Program, analyzing their association with socioeconomic aspects; cigarette smoking and alcohol intake; family history for SH; treatment adherence; awareness of adequate practices to health; and participation in health education groups – involving patients with hypertension and diabetes mellitus, and performance of physical activities in a mid-sized city in Southern Brazil.

571

Original Article

Souza et al.Blood Pressure Control in the Hiperdia Program

Arq Bras Cardiol. 2014; 102(6):571-578

Table 1 – Patients registered in the Hiperdia Program of Novo Hamburgo (RS) — 2011

UBS Hypertension Hypertension + DM Total Stratified sample

Unanswered questionnaires

Answered questionnaires

Santo Afonso 828 155 983 82 7 75

Hamburgo Velho 296 69 365 30 2 28

Hamburgo Velho 225 64 289 24 2 22

Guarani 178 31 209 17 1 16

Canudos 554 135 689 58 5 53

Iguaçu 67 11 78 7 0 7

Lomba Grande 250 68 318 26 2 24

Rondônia 87 14 101 9 1 8

Kephas 219 64 283 24 2 22

Roselândia 128 28 156 13 1 12

Rincão 320 41 361 30 2 28

Kraemer 78 45 123 10 1 9

Redentora 80 15 95 8 1 7

Boa Saúde 211 85 296 25 2 23

Liberdade 201 40 241 20 1 19

TOTAL 3.722 865 4.587 383 30 353

MethodsThis is a cross-sectional study with a territory-based random

sample stratified by Basic Health Unit (Unidade Básica de Saúde – UBS), comprising the Basic Health Care Network of Novo Hamburgo (State of Rio Grande do Sul, Brazil). All 15 UBS of the city were included, as shown in Table 1. A proportional raffle was carried out according to the number of patients enrolled in Hiperdia6 in each UBS, ordered in numbered tables for each unit. The Hiperdia Program was developed by the Ministry of Health for the enrollment, follow-up and assessment of hypertensive patients, generating quantitative reports according to the patients’ age range, gender, medications used, and follow-up of blood pressure. Data inclusion is in charge of the city health departments.

The following parameters were used for the calculation of the sample size: prevalence of systemic hypertension of 28%, 95% CI, and acceptable error of 5%, thus giving a total of 383 patients. Initially, a screening was made in the Hiperdia data base, to remove double-entered patient data due to errors in their name and family name spelling, patients enrolled in more than one UBS, and those diagnosed exclusively with diabetes mellitus. The subjects included were patients 20 years old or older, of both genders, enrolled in the Hiperdia Program, and diagnosed with hypertension (≥140 mmHg × 90 mmHg) or hypertension plus diabetes mellitus (≥130 mmHg × 80 mmHg). Patients institutionalized in hospitals or nursing homes, those imprisoned, or who had moved to other UBS zone or other city when the research questionnaire was administered, were excluded from the study.

The instruments used for data collection comprised a structured questionnaire including questions regarding the

socioeconomic identification of the subject enrolled as hypertensive in Hiperdia, according to the Brazil Economic Classification Criterion (BECC)7; awareness about health care measures; risk factors such as cigarette smoking and sedentary lifestyle; family history; presence of DM; perception of the disease; and treatment adherence as assessed by the Morisky test8. The instrument was administered by trained interviewers, nurses or nursing technicians.

Blood pressure (BP) was measured using a Solidor aneroid device, batch BE15B, certified by Inmettro, according to the technique proposed by the VI Brazilian Guidelines of Systemic Hypertension9. Individual appointments for each study subject were scheduled in their respective UBS with the support of the City Health Department or by means of a domiciliary visit. Two BP measurements were taken; the first one after half the questionnaire had been administered, and the second one, after the questionnaire had been terminated, in the UBS itself or in the patients’ home, when they could not attend the visit in the UBS. Data were collected between June 2010 and April 2011. For the quality control of data collection, the questionnaire was re-administered in 4% of the total sample, also selected in a random fashion according to the proportion of patients in each UBS, thus ensuring that every unit was evaluated. BP was also measured up to five days after the first data collection.

The interviewers participated in preparatory meetings for discussion and training so that the questionnaire would be correctly filled up, by administering it in a pilot study. Sphygmomanometer handling and Korotkoff sound auscultation were trained in practical workshops guided by an instructions manual.

572

Original Article


Arq Bras Cardiol. 2014; 102(6):571-578

Table 2 – Characteristics of the sample of hypertensive patients enrolled in the Hiperdia Program of Novo Hamburgo (2011)

Variables Frequency (%)

Female gender 245 (69.4)

Age, mean ± standard-deviation 63 ± 10

Skin color

White 316 (89.5)

Mixed 16 (4.5)

Black 21 (6.0)

Social class*

B1 + B2 23 (6.5)

C1 86 (24.4)

C2 142 (40.3)

D + E 101 (28.8)

Level of education

Illiterate/Elementary school (1st to 4th) 196 (57.8)

Elementary school (5th to 8th) 125 (36.9)

High school/College 18 (5.3)

Married/living with partner 226 (65.9)

*Social class: Brazil Economic Classification Criterion, 2011.

Data were doubled entered in the Epidata program and analyzed using the Statistical Package for the Social Sciences (SPSS), version 19.0. The analysis included the calculation of measures of frequency; percentage for categorical variables and standard deviation for continuous variables contained in the questionnaire; and BP measurement. The measure of effect used was the prevalence ratio (PR), with 95% confidence interval, and Wald’s χ² test with simple and multiple Poisson regression.

Multivariate analysis was carried out using Poisson regression, considering p < 0.20 for the control of confounding factors, whose variables analyzed were: gender; age; level of education; socioeconomic classification; physical activity; cigarette smoking; time of awareness of hypertension; awareness of healthy habits regarding the use of salt; regular visits to the doctor; alcohol use; and presence of DM.

The research project was approved by the Research Ethics Committee under protocol no. UP 4344/09. All interviewees gave written informed consent.

ResultsThe data from 353 patients diagnosed with SH or SH

plus DM were studied, because 30 individuals of the sample either refused to participate in the research, or had moved, or were institutionalized. Table 2 shows the sociodemographic characteristics of the study sample. Most of the sample was comprised of women (69.4%) and patients older than 60 years (62.1%); 64.7% of the interviewees belonged to social classes C1 and C2; 31% were diagnosed with DM. Blood pressure was not controlled in 63.3% of the hypertensive patients.

In relation to the history of hospitalization in the past two years, 27.1% reported to have been hospitalized for SH or for a related condition. Of these, 4.1% had been hospitalized twice and 1.9%, more than three times.

Of the total of respondents, only 51 reported to participate in groups of hypertensive patients, which represent 47.1% of patients with controlled BP.

Table 3 shows the distribution of variables in relation to BP control as well as crude and adjusted prevalence ratios. In the crude analysis, BP control was significantly associated with the female gender, performance of physical activities, absence of DM, and awareness of the diagnosis of hypertension for less than 10 years.

In the adjusted analysis, only the presence of DM remained as a factor associated with BP control, and only 15.7% of hypertensive patients with diabetes showed controlled BP in comparison to 41% of controlled BP among non-diabetic hypertensive patients (p = 0.011).

Of the hypertensive patients assessed, 96.9% were aware of the diagnosis of SH for 14 ± 9 years and 54.3% reported treatment adherence. There was no statistically significant difference between non-adherent and adherent patients in relation to BP control (p = 0.257).

As regards awareness of important measures to maintain good health, 87% reported to be aware of the importance of a healthy diet, 70.8% reported to be aware that they should control salt intake, and 59.5% said they were aware they should see the doctor regularly (Figure 1).

DiscussionIn this cross-sectional study, we observed that, albeit

receiving antihypertensive treatment, the hypertensive patients assessed showed unsatisfactory blood pressure levels, with low BP control and insufficient treatment adherence. However, they were aware of the importance of adopting good lifestyle practices.

The proportion of patients with controlled BP was similar to that of other studies10,11 corrected for normal BP parameters for hypertensive and diabetic hypertensive patients, and was much lower than that found in individuals seen in community-based services in the United States12, where 71.4% of hypertensive patients were controlled. However, results more similar to ours were found in a study conducted in 26 countries13, with 23.7% of patients with controlled BP. The changes recommended by national8 and international14 guidelines are necessary to improve BP control.

In a study with non-adherent patients3, adherence reached 72.3% after mail interventions. Another study, with Finnish public workers5, found 79.6% of treatment adherence in a cohort that analyzed recordings of pharmacy sales; and yet another, using telephone survey15, reported adherence of 61% of hypertensive patients. Rates of treatment adherence range from 50% to 90% among hypertensives16. In order to improve these rates, it is necessary to implement measures of primary health care17.

A significant association was observed between time of awareness of the diagnosis of systemic hypertension and BP control in the bivariate analysis, but not in the multivariate

573

Original Article


Arq Bras Cardiol. 2014; 102(6):571-578

Table 3 – Variables distribution of patients registered in the Hiperdia Program in relation to controlled BP

N Controlled BP p* value PR (95%CI) Adjusted PR (95%CI) p** value

Gender

Male 108 25% − 1.00 1.00 −

Female 245 37.60% 0.016 1.50 (1.04 a 2.16) 1.50 (0.81 a 2.79) 0.197

Age

< 60 years 133 38.30% − 1.00 1.00 −

≥ 60 years 220 30.90% 0.148 0.81 (0.60 a 1.08) 0.87 (0.57 a 1.33) 0.533

Level of education

Up to 4th grade 196 29.60% − 1.00 1.00 −

High school 125 38.40% 0.099 1.30 (0.95 a 1.77) 0.91 (0.59 a 1.40) 0.657

or above 18 33.30% 0.735 1.13 (0.57 a 2.24) 0.69 (0.26 a 1.82) 0.449

Marital status

Married 226 32.70% − 1.00 − −

Other 117 34.20% 0.787 1.04 (0.76 a 1.43) − −

ABEP Class

B1 + B2 23 34.80% 0.212 1.53 (0.79 a 2.97) 1.95 (0.47 a 8.15) 0.361

C1 86 41.90% 0.006 1.84 (1.19 a 2.84) 2.70 (1.32 a 5.52) 0.006

C2 142 36.60% 0.026 1.61 (1.06 a 2.45) 2.26 (1.22 a 4.54) 0.022

D + E 101 22.80% − 1.00 1.00 −

Physical activity

Do not perform physical activity 64 15.60% − 1.00 1.00 −

Perform physical activity 164 36.00% 0.007 2.30 (1.26 a 4.21) 1.82 (0.95 a 3.45) 0.071

Cigarette smoking

Do not smoke 266 36.10% − 1.00 1.00 −

Smoker 27 25.90% 0.324 0.72 (0.37 a 1.37) 0.92 (0.31 a 2.77) 0.885

Former smoker 60 26.70% 0.187 0.74 (0.47 a 1.16) 0.93 (0.46 a 1.89) 0.839

Alcohol intake

No 332 34.90% − 1.00 1.00 −

Yes 21 14.30% 0.098 0.41 (0.14 a 1.18) 0.62 (0.15 a 2.56) 0.512

Perceived health status

Very good/good/regular 311 34.10% 0.926 1.02 (0.64 a 1.64) − −

Poor/very poor 39 33.30% − 1.00 − −

Diabetes

No DM 245 41.60% < 0.001 2.65 (1.67 a 4.19) 2.39 (1.22 a 4.68) 0.011

With DM 108 15.70% − 1.00 1.00 −

Family history of SH

Negative 145 35.20% − 1.00 − −

Positive 197 34.00% 0.823 0.97 (0.72 a 1.30) − −

Adherence

Adherent 189 36.00% − 1.00 − −

Non-adherent 159 30.20% 0.257 0.84 (0.62 a 1.14) − −

Time of awareness of SH

> 10 years 164 25.60% − 1.00 1.00 −

< 10 years 171 39.20% 0.009 1.53 (1.11 a 2.11) 1.13 (0.71 a 1.78) 0.610

574

Original Article


Arq Bras Cardiol. 2014; 102(6):571-578

Figure 1 – Awareness of relevant measures to keep good health.

7.4

Healthy diet

Control of salt intake

See doctor

Physical exercises

No smoking

No alcohol intake

Stress control

Ideal weight

0 20 40 50%

80 100

87.0

70.8

59.5

22.1

22.1

18.4

10.2

continuation

Participation in groups

Do not participate 299 33.40% − 1.00 − −

Participate 51 35.30% 0.794 1.05 (0.70 a 1.58) − −

Lifestyle change

Healthy diet

Did not mention 46 30.40% − 1.00 − −

Mentioned 307 34.20% 0.622 1.12 (0.71 s 1.79) − −

Salt intake control

Did not mention 103 27.20% − 1.00 − −

Mentioned 250 36.40% 0.108 1.34 (0.94 a 1.91) 1.20 (0.78 a 1.84) 0.418

See doctor

Did not mention 143 28.70% − 1.00 − −

Mentioned 210 37.10% 0.105 1.29 (0.95 a 1.77) 1.03 (0.69 a 1.54) 0.892

*Wald’s χ2 test obtained in the Poisson’s simple regression analysis.**Wald’s χ2 test obtained in the Poisson’s multiple regression analysis.DM: diabetes mellitus; SH: systemic hypertension; CI: confidence interval; BP: blood pressure; PR: prevalence ratio.

analysis. In another study, opposite results were found, with time of awareness of the diagnosis being associated with a poorer blood pressure control18.

Women comprised the major part of our study sample, like in other studies19-22, and they sustained better BP control in comparison to men (25% and 37.6%, respectively). Fucks’s population-based study23 found a greater number of hypertensive women, but a slightly smaller number of individuals above 60 years of age.

The proportion of women and elderly individuals enrolled in Hiperdia is greater than that of population-based studies, precisely because these populations tend to seek health services more frequently. This is important to help guide planning measures in the care of hypertensive patients, with possible active search of less represented populations, such as those of men and patients younger than 60 years of age.

In another study conducted in a group of UBS in São Paulo18, the percentage of BP control among men was 30.9%,

575

Original Article


Arq Bras Cardiol. 2014; 102(6):571-578

and 52.6% among women. These findings were better than ours, but worse than those of patients followed up in an outpatient service in Rio de Janeiro, where only 27% had controlled BP24.

The frequency of diabetes mellitus among the hypertensive patients analyzed was 31%, identical to that of another study13 on the control of hypertension and cardiometabolic risk. Hypertension control, as assessed in a specialized service25, was found in only 13.4% of diabetic hypertensive patients. The presence of diabetes mellitus in hypertensive patients characterizes a scenario in which it is more difficult to control BP according to the parameters elected as ideal by the VI Brazilian Guidelines of Hypertension9. In our study, DM as a comorbidity was associated with worse BP control in hypertensive patients. In view of these findings, we conclude that diabetic hypertensive patients require closer follow-up and support from the health care team and their family in order to adhere to treatment and improve their lifestyle as a condition to achieve better results in their BP control.

The percentage of patients who had attended school up to the 4th grade was 57.8%, and 64.7% among individuals from economic classes C1 and C2. Fuchs et al23, Gus et al26 and Piccini and Victora27 found association between low level of education and hypertension, and stated that poor life conditions predispose to the development of diseases. For Piccini et al28, the level of education was associated with blood pressure control, with worse control among those had attended school for fewer years. This factor, associated with hypertension, may be classified as a modifiable risk factor.

The frequency of cigarette smoking and alcohol intake reported by the hypertensive patients was lower than that usually found in the literature10,18; still, alcohol intake was associated with poorer BP control.

In our study, more than half of the interviewees reported not to perform physical activities. This corroborates the findings of other studies10,18,29. Nonetheless, albeit reaching borderline significance in the adjusted analysis, physical activity contributed to BP control.

In our study, it was not possible to compare patients participating in groups of hypertensive individuals with those not participating, due to the low attendance rate and small number of groups formed in the UBS, where only 14.4% of the respondents reported to participate in group activities in the past year. This intervention has been proved useful in the control of these chronic diseases18,29,30.

We found evidences that most of the hypertensive patients remain with inadequate BP control, especially those also diagnosed with DM. The latter have an almost three-time higher possibility of not having controlled BP in comparison to those diagnosed with SH alone, like observed in the ACCORD study31, therefore deserving careful attention on the part of health care teams. Diabetic hypertensive patients have a two- to six-time higher risk of cardiovascular death than hypertensive patients without diabetes32.

An effective patient follow-up is one of the most difficult goals to achieve in Hiperdia, whether due to the physical distance between patients and the health care services, or to difficulties reported by professionals to reach these patients in their homes, or also due to the lack of patient awareness regarding SH and

DM. Also, these patients are strongly linked to factors of social vulnerability such as low level of education and lack of contact with the health care team; thus, the change in this panorama falls on the primary health care teams, with promotion and prevention actions, especially among diabetic hypertensive patients33.

It is important to consider possible study limitations characterized by measurement bias; current cigarette smoking and alcohol intake, whose percentages were much lower than those found in the literature; a possible influence of the observer, of the data collection environment, of the device used, and, finally, of the white coat effect. As regards the performance of physical activities, reverse causality bias may have occurred. Selection bias may also have occurred because the Hiperedia recordings of the 15 UBS do not include all hypertensive patients living in Novo Hamburgo. With the use of the Morisky test, recall bias may have occurred regarding the accuracy of the responses to the test. However, the findings showed low adherence, which seems to reflect real life.

Further research on Hiperdia and BP control is still necessary in the Brazilian Southern region. Our findings will help plan actions to improve the access of Hiperdia users to primary health care measures, such as: monitoring of diabetic hypertensive patients through monthly visits of community health care agents; quantitative and qualitative assessment of Hiperdia recordings, aiming to improve patient enrollment; implementation of the recommendations of the VI Guidelines of SH9, especially for diabetic hypertensive patients; automation of UBSs for full operation of the enrollment system; enrollment in the Health Clubs Project of the Ministry of Health; training of multidisciplinary teams (NASF); and enrollment in the Care of people with Chronic Diseases Network of the Ministry of Health34.

Based on our findings, we can conclude that blood pressure control in the patients studied is unsatisfactory and that this control is even harder in diabetic patients. Thus, a policy of emphasis on this group of patients should be developed.

Author contributionsConception and design of the research, Analysis and

interpretation of the data, Statistical analysis, Writing of the manuscript and Critical revision of the manuscript for intellectual content: Souza CS, Stein AT, Bastos GAN, Pellanda LC; Acquisition of data: Souza CS, Bastos GAN; Obtaining financing: Pellanda LC.


reported.

Sources of Funding This study was funded by Fundo de apoio à pesquisa do

ICFUC (FAPICC).

Study Association This article is part of a thesis submitted by Clarita Silva

de Souza to obtain her masters´degree from Instituto de Cardiologia/Fundação Universitária de Cardiologia do Rio Grande do Sul.

576

Original Article


Arq Bras Cardiol. 2014; 102(6):571-578

1. Casado L, Viana LM, Thuler LC. Fatores de risco para doenças crônicas não transmissiveis no Brasil: uma revisão sistemática. Rev Bras Cancerol. 2009;55(4):379-88.

2. Aronow WS. Treatment of systemic hypertension. Am J Cardiovasc Dis. 2012;2(3):160-70.

3. Jing S, Naliboff A, Kaufman MB, Choy M. Descriptive analysis of mail interventions with physicians and patients to improve adherence with antihypertensive and antidiabetic medications in a mixed-model managed care organization of commercial and Medicare members. J Manag Care Pharm. 2011;17(5):355-66.

4. Cordero A, Bertomeu-González V, Moreno-Arribas J, Agudo P, López-Palop R, Masiá MD, et al. Burden of systemic hypertension in patients admitted to cardiology hospitalization units. Am J Cardiol. 2011;108(11):1570-5.

5. Oksanen T, Kawachi I, Kouvonen A, Suzuki E, Takao S, Sjösten N, et al. Workplace social capital and adherence to antihypertensive medication: a cohort study. PloS One. 2011;6(9):e24732.

6. Brasil. Ministério da Saúde. Departamento de Informação e Informática do Sistema Único de Saúde (Datasus). Sistema de Informação Hiperdia [on-line]. [Acesso em 2011 out. 20] Disponivel em: http:/hiperdia.datasus.gov.br.

7. Associação Brasileira de Empresas de Pesquisa. Critério de Classificação Econômica Brasil [on-line]. 2011. [Acesso em2011 set.12 ] Disponivel em: www.abep.org/novo/Content.aspx?ContentID=302.

8. Ben AJ, Neumann CR, Mengue SS. Teste de Morisky-Green e Brief Medication Questionare para avaliar adesão a medicamentos. Rev Saúde Pública. 2012;46(2):279-89.

9. Sociedade Brasileira de Cardiologia, Sociedade Brasileira de Hipertensão, Sociedade Brasileira de Nefrologia. VI Diretrizes brasileiras de hipertensão. Arq Bras Cardiol. 2010;95(1 supl.1):1-51.

10. Lima LM, Schwartz E, Muniz RM, Zilmer JG, Ludtke I. Perfil dos usuários do Hiperdia de tres unidades básicas de saúde do sul do Brasil. Rev gaúch enferm. 2011;32(2):323-9.

11. Santa Helena ET, Nemes MI, Eluf Neto J. Avaliação da assistencia a pessoas com hipertensão arterial em Unidades de Estratégia Saúde da Familia. Saude Soc São Paulo. 2010;19(3):614-26.

12. Romanelli RJ, Schiro TA, Jukes T, Wong KS, Ishisaka DY. Disparities in blood pressure control within a community-based provider network: an exploratory analysis. Ann Pharmacotter. 2011;45(12):1473-82.

13. Thoenes M, Bramlage P, Zhong S, Shang S, Volpe M, Spirk D. Hypertension control and cardiometabolic risk: a regional perspective. Cardiol Res Pract. 2012;2012:925046.

14. National Institute for Health and Clinical Excellence – NICE. Prevetion of cardiovascular disease at population level [on-line]. 2010 [acesso em 2011 out.20] Disponivel em: http://www.nice.org.uk/guidance/PH25.

15. Nair KV, Belletti DA, Doyle JJ, Allen RR, McQueen RB, Saseen JJ, et al. Understanding barriers to medication adherence in the hypertensive population by evaluating responses to a telephone survey. Patient Prefer Adherence. 2011;5:195-206.

16. Bugalho A, Carneiro AV. Intervenções para aumentar a adesão terapeutica em patologias crônicas. Lisboa: Centro de Estudos de Medicina Baseada em Evidencia;2004.p.9-16.

17. Souza LG, Menandro MC. Atenção primária à saúde: diretrizes, desafios e recomendações. Revisão de bibliografia internacional. Physis. 2011;21(2):517-39.

18. Pierin AM, Marroni SN, Taveira LA, Benseñor IJ. [Hypertension control and related factors at primary care located in the west side of the city of São Paulo, Brazil]. Cien Saúde Colet. 2011;16 Suppl 1:1389-400.

19. Rosário TM, Scala LC, França GV, Pereira MR, Jardim PC. Prevalencia, controle e tratamento da hipertensão arterial sistemica em Nobres — MT. Arq Bras Cardiol. 2009;93(6):672-8.

20. Duarte MT, Cyrino AP, Cerqueira AT, Nemes MI, Iyda M. Motivos do abandono do seguimento médico no cuidado a portadores de hipertensão arterial: a perspectiva do sujeito. Cienc Saúde Coletiva. 2010;15(5):2603-10.

21. Cesarino CB, Cipullo JP, Martin JF, Ciorlia LA, Godoy MR, Cordeiro JA, et al. Prevalencia e fatores sociodemográficos em hipertensos de São José do Rio Preto - SP. Arq Bras Cardiol. 2008;91(1):29-35.

22. Rosini N, Machado MJ, Xavier HT. Estudo da prevalencia e multiplicidade de fatores de risco cardiovascular em individuos hipertensos da cidade de Brusque, SC, Brasil. Arq Bras Cardiol. 2006;86(3):219-22.

23. Fuchs FD, Moreira LB, Moraes RS, Bredemeier M, Cardozo SC. Prevalencia de hipertensão arterial sistemica e fatores associados na região urbana de Porto Alegre. Estudo de base populacional. Arq Bras Cardiol. 1994;63(6):473-9.

24. Muxfeldt ES, Nogueira Ada R, Salles GF, Bloch KV. Caracteristicas clinicas e demográficas dos pacientes hipertensos acompanhados no ambulatório de clinica médica de um hospital universitário na cidade do Rio de Janeiro. São Paulo Med J. 2004;122(3):87-93.

25. Freitas JB, Tavares A, Kohlmann O Jr, Zanel la MT, Ribeiro AB. Estudo transversal sobre o controle da pressão arterial no serviço de nefrologia da Escola Paulista de Medicina — Unifesp. Arq Bras Cardiol. 2002;79(2):123-8.

26. Gus I, Harzhein E, Zaslavsky C, Medina C, Gus M. Prevalencia da hipertensão arterial sistemica no Rio Grande do Sul e fatores de risco associados. Arq Bras Cardiol. 2004;83(5):424-8.

27. Piccini RX, Victora CG. Hipertensão arterial sistemica em área urbana no sul do Brasil: prevalencia e fatores de risco. Rev Saúde Pública. 1994;28(4):261-7.

28. Piccini RX, Facchini LA, Tomasi E, Siqueira FV, Silveira DS, Thumé E, et al. Promoção, prevenção e cuidado da hipertensão arterial no Brasil. Rev Saúde Pública. 2012;46(3):543-50.

29. Teixeira ER, Silva JC, Lamas AR, Matos RM. O estilo de vida do cliente com hipertensão arterial e o cuidado com a saúde. Esc Anna Nery Rev Enferm. 2006;10(3):378-84.

30. Silva TR, Feldmam C, Lima MH, Nobre MC, Domingues RZ. Controle de diabetes mellitus e hipertensão arterial com grupos de intervenção educacional e terapeutica em seguimento ambulatorial de uma Unidade Básica de Saúde. Saúde e Sociedade. 2006;15(3):180-9.

31. Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, et al; ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575-85.

32. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Petersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348(5):383-93.

33. Carvalho Filho FS, Nogueira LT, Viana LM, Costa AC, Silva AC. Programa Hiperdia: uma análise de aspectos de vulnerabilidade de usuários da atenção primária à saúde [on-line]. 2012 [Acesso em 2012 set.14]. Disponivel em: http://189.75.118.68/cbcenf/sistemainscricoes/arquivosTrabalhos/I38083.E10.T7279.D6AP.pdf.

34. Brasil. Ministério da Saúde. Secretaria de Atenção à Saúde (SAS). Consulta pública n.º 13 e 16, de 24 de setembro de 2012 [on-line]. [Acesso em 2012 nov.10]. Disponivel em: http://portalsaude.saude.gov.br/portalsaude/arquivos/pdf/2012/Set/25/cp16.pdf.

References

577

Original Article


Arq Bras Cardiol. 2014; 102(6):571-578 578

Original Article

Baroreflex Sensitivity and its Association with Arrhythmic Events in Chagas DiseaseAstrid Meireles Santos, Mauricio Ibrahim Scanavacca, Francisco Darrieux, Bárbara Ianni, Sissy Lara de Melo, Cristiano Pisani, Francisco Santos Neto, Eduardo Sosa, Denise Tessariol HachulInstituto do Coração - HC – FMUSP, São Paulo, SP - Brazil

Mailing Address: Denise Tessariol Hachul •Rua Joaquim Cândido de Azevedo Marques, 1205, Morumbi. Postal Code: 05688-021, São Paulo, SP – Brazil.E-mail: [email protected]; [email protected] Manuscript received August 8, 2013; revised manuscript January 13, 2014; accepted January 24, 2014.

DOI: 10.5935/abc.20140066

Abstract

Background: Sudden death is the leading cause of death in Chagas disease (CD), even in patients with preserved ejection fraction (EF), suggesting that destabilizing factors of the arrhythmogenic substrate (autonomic modulation) contribute to its occurrence.

Objective: To determine baroreflex sensitivity (BRS) in patients with undetermined CD (GI), arrhythmogenic CD with nonsustained ventricular tachycardia (NSVT) (GII) and CD with spontaneous sustained ventricular tachycardia (STV) (GIII), to evaluate its association with the occurrence and complexity of arrhythmias.

Method: Forty-two patients with CD underwent ECG and continuous and noninvasive BP monitoring (TASK force monitor). The following were determined: BRS (phenylephrine method); heart rate variability (HRV) on 24-h Holter; and EF (echocardiogram).

Results: GIII had lower BRS (6.09 ms/mm Hg) as compared to GII (11.84) and GI (15.23). The difference was significant between GI and GIII (p = 0.01). Correlating BRS with the density of ventricular extrasystoles (VE), low VE density (<10/h) was associated with preserved BRS. Only 59% of the patients with high VE density (> 10/h) had preserved BRS (p = 0.003). Patients with depressed BRS had higher VE density (p = 0.01), regardless of the EF. The BRS was the only variable related to the occurrence of SVT (p = 0.028).

Conclusion: The BRS is preserved in undetermined CD. The BRS impairment increases as disease progresses, being more severe in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with EF, but with the density and complexity of ventricular arrhythmias. (Arq Bras Cardiol. 2014; 102(6):579-587)

Keywords: Chagas Disease; Arrhythmias, Cardiac; Death, Sudden; Baroreflex / physiology; Analysis of Variance.

IntroductionThe arrhythmogenic form of chronic Chagas heart

disease has a high ventricular arrhythmia density, which not only causes symptoms1, but is a frequent cause of sudden death (SD)2,3. It is worth noting the scarcity of symptoms and the normal cardiac size in contrast to the anatomicopathological changes found4. Determining the mechanism of SD in Chagas disease remains a challenge. However, evidence has shown that, because it is a fibrosing pathology5,6, the appearance of unidirectional block and slow conduction zones is common, which is the ideal scenario for reentrant ventricular arrhythmias, which can be confirmed during programmed ventricular stimulation7-10.

Of the factors that contribute to the occurrence of malignant ventricular arrhythmias, in addition to myocardial structural abnormalities, ventricular extrasystoles (VE), which initiate the reentrant process, stand out. However, not every patient with ventricular arrhythmia dies suddenly. Probably the model is only complete when functional factors appear, favoring the occurrence of arrhythmias (heart baroreflex control and autonomic dysfunction supposed to play an important role in the genesis of sudden death)11-14. The following tools of cardiovascular autonomic evaluation have been used: analysis of baroreflex sensitivity (BRS), which quantifies the incremental capacity of vagal activity; and heart rate variability (HRV), which assesses the tonic vagal activity on the heart. The BRS has been consolidated as an independent marker of mortality risk in ischemic patients, being used as a clinical and prognostic tool in a variety of cardiovascular diseases.

Special attention should be given to the asymptomatic subgroup, which, despite the lack of triggering factors or of structural myocardial changes, corresponds to a significant number of cases of SD15-17.

The autonomic dysfunction of Chagas disease can be detected prior to ventricular dysfunction, at all phases of the disease18,19. Thus, the detailed study of the autonomic

579

Original Article

Santos et al.Baroreflex sensitivity in Chagas disease

Arq Bras Cardiol. 2014; 102(6):579-587

function in several forms of Chagas disease is mainly aimed at determining possible elements that can identify individuals at risk for developing complex arrhythmias and/or SD.

Objective The primary objective of this study was to determine

BRS in patients with the following forms of Chagas disease: undetermined (Group I); arrhythmogenic with nonsustained ventricular tachycardia (NSVT) (Group II); arrhythmogenic with spontaneous sustained ventricular tachycardia (SVT) (Group III). In addition, it was aimed at assessing the association between ventricular arrhythmia severity and the impairment degree of BRS.

The secondary objective was to assess the HRV by using 24-hour Holter monitoring, and, by using Doppler two-dimensional echocardiography, the left ventricular ejection fraction (LVEF) and the dimensions of cardiac left cavities.

Case series and methodsThis study selected 42 individuals with positive serology

for Chagas disease, confirmed by the presence of at least two serologic reactions (indirect hemagglutination, indirect immunofluorescence or immunoenzymatic assay – ELISA), mainly originated from the outpatient clinic of the Instituto do Coração, of the Hospital das Clinicas of the Medical School of the Universidade de São Paulo (InCor-FMUSP) (Clinical Unit of Arrhythmia and Unit of Cardiomyopathies). The research protocol was approved by the Scientific Committee of the InCor-FMUSP and the Committee on Ethics and Research (CAPPesq) of the InCor-FMUSP.

The individuals were divided into three groups: Group I (GI), individuals with the undetermined form of Chagas disease; Group II (GII), patients with Chagas disease and complex ventricular arrhythmia, including NSVT; Group III (GIII), patients with Chagas disease and complex ventricular arrhythmia and at least one spontaneous SVT recording, after preliminary cardiological evaluation with 12-lead electrocardiogram, echocardiogram, 24-hour Holter monitoring and exercise testing. The undetermined form of the disease was defined according to the already established criteria: asymptomatic individuals with at least two positive serological tests for Chagas disease and normal results of electrocardiogram, chest X-ray and esophageal and colon contrast-medium tests20. The ventricular arrhythmia recordings for inclusion in G II and GIII came from previous tracings of 24-hour Holter and 12-lead electrocardiogram performed at emergency rooms or triggered during exercise testing.

Group I comprised 16 individuals [11 (68.75%) females and 5 (31.25%) males]. Group II comprised 19 patients [14 females (73.68%) and 5 males (26.32%)] as follows: 17 with NSVT recorded on 24-hour Holter and 2 recorded during exercise testing. Group III comprised 7 patients [4 (57.14%) females and 3 (42.86%) males] as follows: 5 with SVT recorded on 12-lead electrocardiogram and 2 recorded on 24-hour Holter.

All GI patients were asymptomatic, while 84.2% of GII and 43% of GIII patients had symptoms, the most frequent being palpitations, dyspnea and chest pain. Syncope was reported by two GII individuals. Of the 7 GIII individuals, 3 had unstable SVT, requiring electrical cardioversion.

The medicines, such as beta-blockers, calcium channel blockers, digoxin and aldosterone antagonists, were suspended for at least three half-lives before the procedure, and the patients were instructed to have a light caffeine-free breakfast, in addition to avoid alcoholic beverage in the 24 hours preceding the exam.

Noninvasive cardiovascular monitoring was performed with the Task Force® Monitor system (CNSysteSD Medizintechnik GmbH, version 2.2.12.0, Austria)21. The parameters assessed were HRV, systolic and diastolic blood pressure (SBP and DBP, respectively) and BRS, blood pressure (BP) being measured via digital photoplethysmography22,23 and electrocardiogram acquired by using three adhesive electrodes attached to the chest, to analyze the intervals between R waves (R-R intervals). A digital cuff with continuous pressure was positioned around the middle phalanx of the right third and fourth fingers, and another, on the left forearm. The oscillometric measures of BP were transformed into absolute values for each consecutive beat. The acquired signs were shown on screen, and, by the end of the procedure, they were printed or stored in a file under a format of easy conversion.

After a rest period, consecutive, continuous 15-minute recordings of SBP and HR were obtained for spontaneous BRS analysis, which was performed according to the sequence methodology24. That methodology involves a computer program and is based on the identification, on the time domain, of the spontaneous occurrence of sequences of at least three consecutive heartbeats, in which there is a progressive increase of SBP and consequent R-R interval prolongation or a progressive decrease of SBP and consequent R-R interval shortening. To be considered by the program, the modifications in SBP and R-R interval should be equal to or greater than 1 mm Hg and 5 ms, respectively. Linear regression was applied to all sequences, and the mean of the values obtained in all sequences was calculated for each patient, representing the measure of spontaneous BRS (in ms/mm Hg). Those values were automatically provided by the Task Force ® Monitor system.

After spontaneous BRS recording, the volunteers had their BP and HR continuously monitored, as previously described. Then, phenylephrine was infused rapidly (30 seconds) and intravenously, at the dose of 2-4 mcg/kg, in at least three bolus, at 10-minute intervals, to increase SBP by 15 to 40 mm Hg25. If SBP did not increase as expected (> 15 mm Hg), a new infusion was performed with 25-50 increments up to the maximum dose of 10 mcg/kg.

Consecutive SBP values and corresponding changes in R-R intervals (with beat delay) were plotted, resulting in the slope of a line of linear regression. The measures chosen for analysis were those with a strong linear correlation coefficient (coefficient r ≥ 0.7). The BRS measure considered (expressed as ms/mm Hg) was equivalent to the calculated mean of the values obtained in the infusions with the greatest reproducibility for each patient (semiautomatic method).

The following dimensions of the left cardiac cavities were assessed on echocardiography and expressed in millimeters (mm): end-systolic left ventricular diameter (ESLVD); end-diastolic left ventricular diameter (EDLVD); and left atrial diameter (LAD). Ejection fraction (EF) was calculated by using the Teichholz method26.

580

Original Article


Arq Bras Cardiol. 2014; 102(6):579-587

Statistical analysisData were organized in tables, graphs and charts of

descriptive measures. For inferential statistical analysis, the following tests were performed: Kolmogorov-Smirnov test, aimed at analyzing the normality of the BRS variable; and Levene’s test to assess the equality of the variances for the three groups. The means of the groups were compared by use of analysis of variance (ANOVA), and multiple comparisons used Tukey test (equal variances) or Games-Howell test (unequal variances). Pair analysis was performed with Student t test.

The correlation between continuous variables was performed with Pearson linear correlation coefficient (r), and the association between categorical variables, by use of chi-square test or maximal likelihood ratio. The odds ratio (OR) and their confidence intervals (95%CI) for SVT and probable factors influencing its appearance were calculated. Backward stepwise logistic regression analysis was performed, and the final adjusted model was obtained with a 5% significance level. Analyses with p < 0.05 were considered statistically significant.

The SPSS software, version 14.0, was used for data processing.

ResultsGroup I comprised 16 individuals, GII, 19 patients, and

GIII, 7 patients. No significant difference was observed between the groups regarding sex distribution. The mean ages in the groups were as follows: GI, 49.5 years; GII, 50.26 years; and GIII, 41.86 years. Table 1 shows the clinical characteristics of the groups.

Statistically significant differences were observed between GI and GIII regarding EDLVD (p = 0.001), and between the three groups regarding ESLVD.

Regarding LVEF, statistical difference was observed between GI and GIII (p = 0.000), and between GII and GIII (p = 0.02).

24-hour HolterGraph 1 shows the distribution and density of VE observed

on 24-hour Holter monitoring. The greatest ventricular ectopia density was found in GII.

Measures of spontaneous BRSTable 2 shows the characteristics of the groups studied

regarding spontaneous BRS.

Measures of induced baroreflex sensitivity Statistically significant difference was observed between

the groups regarding the assessment of BRS in response to phenylephrine (Table 3).

After comparing the groups, statistically significant difference was observed between GI and GIII (p = 0.01), but no difference was observed between GI and GII. Pearson’s correlation coefficient r was used to assess the correlation between the variables. Correlating BRS and density of ventricular ectopias, a higher density of ventricular ectopias (p = 0.01) was observed in the subgroup with moderately depressed BRS (3.0 – 6.0 ms/mm Hg). A positive association between low ventricular ectopia density and preserved BRS was also observed (p = 0.003) (Graph 2).

Table 1 – Clinical data of the sample studied (n = 42)

GI GII GII P

Age (years) 49.50 ± 6.70 50.26 ± 7.65 41.86 ± 7.66 0. 037

BMI (kg/m2) 25.70 ± 3.09 26.50 ± 4.09 23.67 ± 5.55 0. 293

Race (B/NB) (16/00) (18/01) (7/00) -

SBP (mm Hg) 115.94 ± 14.74 117.26 ± 14.74 117.14 ± 7.55 0. 943

DBP (mm Hg) 75.00 ± 8.16 76.58 ± 8.17 71.43 ± 12.15 0. 431

HR (beats/min) 70.99 ± 6.29 68.53 ± 9.31 58.43 ± 7.20 0.003

NYHA FC I 100% 94.7% 85.7% 0.286

Mean VE/24 h 6.8 255.39 49.5 -

LVEF (%) 68.63 ± 8.29 59.37 ± 13.08 44.86 ± 14.98 < 0. 0001

EDLVD (mm) 48.13 ± 4.09 52.95 ± 6.74 59.29 ± 7.45 0. 001

ESLVD (mm) 30.50 ± 3.46 36.79 ± 8.46 44.86 ± 8.74 < 0. 0001

LAD (mm) 33.94 ± 3.15 36.21 ± 5.77 36.14 ± 5.46 0.357

Amiodarone (200 mg/d) 0 (0%) 3 (15.8%) 3 (42.9%) 0. 016

Amiodarone (400 mg/d) 0 (0%) 0 (0%) 3 (42.9%) 0. 002

Values shown as mean ± SD; GI: group I; GII: group II; GIII: group III; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; NYHA FC: New York Heart Association functional class (%); ESLVD: end-systolic left ventricular diameter; EDLVD: end-diastolic left ventricular diameter; LVEF: left ventricular ejection fraction (%); LAD: left atrial diameter.

581

Original Article


Arq Bras Cardiol. 2014; 102(6):579-587

Graph 1 – Distribution of ventricular extrasystoles (VE) in the groups studied.

Table 2 – Characterization of the groups studied regarding spontaneous baroreflex sensitivity (ms/mm Hg)

Descriptive measures

Group n Mean ± SD Minimum Maximum

GI 13 13.38 ± 5.08 6.34 23.32

GII 18 12.95 ± 4.29 5.93 21.04

GIII 5 9.54 ± 3.63 3.25 12.21

Note: values expressed as mean ± standard deviation; GI: group I; GII: group II; GIII: group III. p = 0.265

Table 3 – Measures of baroreflex sensitivity (BRS) in the groups studied (ms/mm Hg)

Descriptive measures

Group n Mean ± SD Minimum Maximum

GI 16 15.23 ± 7.61 6.12 30.27

GII 19 11.84 ± 6.62 3.08 27.65

GIII 7 6.09 ± 3.38 2.78 10.84

Note: values expressed as mean ± standard deviation; GI: group I; GII: group II; GIII: group III. p = 0,01

582

Original Article


Arq Bras Cardiol. 2014; 102(6):579-587

Graph 2 – Correlation between the measure of baroreflex sensitivity (BRS) and density of ventricular arrhythmias.Note: BRS: baroreflex sensitivity; LV ectopia > 10/h: left ventricular ectopia greater than 10 per hour; LV ectopia < 10/h: left ventricular ectopia smaller than 10 per hour.

The variables BRS, LVEF, EDLVD and VE/h were tested in the logistic regression model. After multivariate analysis, BRS was the only variable related to SVT appearance (p = 0.028).

Discussion Sudden death is the major cause of death in Chagas disease,

present in 55% to 65% of the cases27. It is worth noting that many of such SD affect patients with normal or close-to-normal left ventricular function. The risk of SD is known not to be the same for all patients with Chagas disease. Participation of the autonomic nervous system, mainly decreased parasympathetic activity, has been evidenced as a contributing factor in the genesis of ventricular arrhythmias and SD in ischemic heart disease28. Early identification of patients with chronic Chagas heart disease at risk of developing potentially lethal arrhythmic events is extremely important29, and autonomic function determination could be used as a noninvasive method for risk stratification in that population.

In this study, the three groups of patients did not differ regarding most of the clinical characteristics evaluated. However, the mean age of GIII patients (41.86 years) was lower than those of GI and GII patients (49.50 and 50.26 years, respectively). Vagal activity is known to decrease with age in healthy individuals. In our case series, GIII patients, although younger and probably with a shorter exposure to disease, showed a more impaired parasympathetic activity, in addition to higher arrhythmia complexity, which is in accordance with the findings of the ATRAMI study30. That study encompassed 1284 patients with recent myocardial infarction, whose HRV had been quantified as standard deviation of normal to normal RR intervals (SDNN) and BRS measurement with the phenylephrine method. The BRS measurement had

no prognostic value in the subgroup of patients older than 65 years; however, it showed a strong statistical power in the younger subgroup. Thus, advanced age was an exclusion criterion in our population.

Our observations reveal a way to identify worse disease progression, since GIII patients had more severe clinical manifestations, although they were younger, most in functional class I and with relatively preserved ventricular function. Our data revealed that, although most patients studied had preserved EF, the means were lower in GIII as compared with those in GI and GII, the same occurring with EDLVD. The clinical progression of the disease is dynamic, involving both autonomic function deterioration and progressive structural myocardial impairment. It is still unknown to what extent those two factors develop concomitantly or in an independent way. Further more detailed studies assessing the interdependence between structural and autonomic injuries are required.

Phenylephrine-induced baroreflex sensitivityIn our study, phenylephrine-induced BRS was significantly

reduced in the subgroup of patients with more complex arrhythmia (GIII), such as spontaneous SVT. It is worth noting that those changes in baroreflex were mainly shown in patients with NYHA functional class I. Over the past two decades, cardiac BRS has been recognized as a cardiovascular risk marker. The first clinical evidence has been identified in a study performed with 78 patients after myocardial infarction³¹, whose BRS was assessed in a 24-month follow-up. All 7 patients dead during follow-up had an extremely decreased BRS. However, that method has been consolidated as an independent marker of mortality risk in ischemic patients only after the multicenter

583

Original Article


Arq Bras Cardiol. 2014; 102(6):579-587

ATRAMI study30. Since then, it has been largely used for risk stratification in several populations, such as those with hypertension, diabetes and dilated cardiomyopathies.

In chronic Chagas heart disease, the autonomic nervous system involvement, both sympathetic and parasympathetic, has been well demonstrated from the histopathological and functional viewpoints. However, only a few studies have used BRS as a marker of the autonomic function in that population, and, to our knowledge, it has not been used to stratify the risk of arrhythmic events. Autonomic dysfunction is more exuberant in the cardiodigestive and digestive forms of the disease³². However, in the undetermined form of Chagas disease, the autonomic function assessment has conflicting results, which have varied from the single sympathetic or mainly parasympathetic involvement³³, to no impairment at all. Junqueira Júnior et al.³², in 1985, demonstrated that BRS was significantly lower in 14 chagasic patients as compared with a control group (healthy); however, when only patients with the undetermined and digestive forms of the disease were studied, BRS was normal. In 2004, Villar et al.34, studying 31 asymptomatic chagasic patients, one group with electrocardiographic changes and the other with no changes, concluded that cardiovagal dysfunction can be early documented by measuring BRS, even in those with no electrocardiographic changes. In addition, they showed that cardiac autonomic assessment could be useful to identify subclinical disease.

In 1998, Marin Neto et al.19, assessing 31 chagasic patients at the initial phase of the disease, studied cardiac autonomic control and biventricular function by using radionuclide angiography, Valsalva maneuver, tilt testing and BRS. Their results showed that cardiac autonomic dysfunction is prominent in patients with the digestive form, but not in those with the undetermined form of the disease. In our case series, patients with the undetermined form showed preserved BRS measures.

Spontaneous baroreflex sensitivity Our results showed greater impairment of spontaneous BRS

in GIII patients. Despite being only a tendency, such difference should be valued. Considering GI, GII and GIII and based on spontaneous BRS determination, autonomic impairment increases as disease progresses.

In addition to being simple and easily obtained, an advantage of the method is that it is based on standardized, automated and computerized measures, which almost eliminate the intra- and interobserver variations. The sequence methodology used to determine spontaneous BRS was applied in this study. According to Parlow et al.24, the method reflects primarily the baroreflex control of cardiac vagal activity (because most sequences are smaller than six beats) and was proposed as a reliable alternative to determine BRS in healthy35 and in hypertensive patients36. However, despite the strong linear association, the agreement between spectral measures and phenylephrine in estimating BRS is weak. The baroreflex response to the sinus node is believed to be different under the influence of different methodologies37. Although provocation with vasoactive drugs has been considered the gold-standard method to assess BRS, the use of those drugs can cause

mechanical changes in the arterial wall, where baroreceptors are located, and result in a more intense and less physiological stimulus of reflex HR adaptation in face of a BP change24. By using the vasoactive drug, relatively greater BP changes are observed, and can alter not only the linear portion of the stimulus-response curve, but can also reach the portions where baroreceptor activity approaches saturation, and where the BRS is lower24. Another contributing factor is the fact that BP changes in spontaneous measurements have smaller amplitudes, and, thus, the method cannot assess the baroreflex function in its entire extension24. Thus, both techniques are considered non-exclusionary, but complementary, in assessing baroreflex function.

The correlations Previewing the occurrence of sustained ventricular

arrhythmias in individuals with preserved ventricular function is a great challenge in chagasic cardiomyopathy, because of the high risk of SD in that population. The high density of ventricular ectopias and the presence of NSVT are known predictive criteria of cardiovascular risk in ischemic patients. However, in chagasic patients with relatively preserved ventricular function, its significance remains controversial.

Rassi et al.38 have recently published a score to stratify the mortality risk of chagasic patients. In that cohort, the authors have found, after uni- and multivariate analyses, six clinical variables that predict poor prognosis, such as NSVT. In addition, they have reported that the combination of NSVT with left ventricular dysfunction was associated with a 15-time greater risk of death in the patients studied.

Our data revealed a direct correlation between the autonomic dysfunction degree and the density of ventricular ectopias on 24-hour Holter monitoring. In addition, 100% of the patients with preserved BRS (> 6.0 ms/mm Hg) had density of ventricular ectopias smaller than 10 per hour, being then considered at lower risk for events39. An inverse correlation between the SDNN index and the density of ventricular ectopias was also observed.

When assessing different noninvasive methods of risk stratification for a certain cardiovascular condition, data regarding ischemic cardiopathy are usually extrapolated from the literature. However, the pathophysiological peculiarities of chagasic cardiomyopathy are not necessarily comparable to those of coronary arterial disease or dilated disease of other etiologies.

Up to now, there is no method that alone can definitively predict the risk of ventricular arrhythmias and of SD in the most varied clinical situations, in the different populations studied. In addition, the cardiovascular risk has not evolved in a linear way, changing with disease progression and/or the treatment used. Therefore, the combination of various tests available is the best way to increase the risk stratification accuracy, and, consequently, to optimize the treatment and cost-effectiveness of therapeutic interventions.

Conclusions Baroreflex sensitivity is preserved in the undetermined

form of Chagas disease. The BRS impairment is progressive

584

Original Article


Arq Bras Cardiol. 2014; 102(6):579-587

1. Rassi Jr A, Rassi AG, Rassi SG, Rassi Jr L, Rassi A. Relação entre sintomas, disfunção ventricular e arritmia ventricular na cardiopatia chagásica crônica. Arq Bras Cardiol. 1992;59(supl 2):182.

2. Rassi A. Curva atuarial da taquicardia ventricular sustentada na cardiopatia chagásica crônica. Anais do IV Simpósio Brasileiro de Arritmias Cardiacas. Recife, 1987.

3. Prata A. Clinical and epidemiological aspects of Chagas disease. Lancet Infec Dis. 2001;1(2):92-100.

4. Lopes ER, Chapadeiro E. Morte súbita em área endemica da doença de Chagas. Rev Soc Bras Med Trop. 1982;16(2):79-84.

5. Dias E, Laranja FS, Miranda A Nobrega G. Chagas’ disease: a clinical, epidemiologic and pathologic study. Circulation. 1956;14(6):1035-60.

6. Barretto AC, Higuchi ML, da Luz PL, Lopes EA, Bellotti G, Mady C, et al. Comparação entre alterações histológicas da miocardiopatia da doença de Chagas e cardiomiopatia dilatada. Arq Bras Cardiol. 1989;52(2):79-83.

7. Mendoza I, Camardo J, Moleiro F, Castellanos A, Medina V, Gomez J, et al. Sustained ventricular tachycardia in chronic myocarditis: electrophysiologic and pharmacologic characteristics. Am J Cardiol. 1986;57(6):423-7.

8. De Paola AA, Horowitz LN, Miyamoto MH, Pinheiro R, Ferreira DF, Terzian AB, et al. Angiographic and electrophysiologic substrates of ventricular tachycardia in chronic chagasic myocarditis. Am J Cardiol. 1990;65(5):360-3.

9. Giniger AG, Retyk EO, Laiño RA, Sananes EG, Lapuente AR. Ventricular tachycardia in Chagas’disease. Am J Cardiol. 1992;70(4):459-62.

10. Sarabanda AV, Sosa E, Scanavacca M, Magalhães L, Kuniyoshi R, Darrieux F, et al. Caracteristicas da indução da taquicardia ventricular sustentada durante a estimulação ventricular programada na cardiopatia chagásica crônica. Arq Bras Cardiol. 1994;63(supl 1):124.

11. Junqueira Junior LF. Sobre o possivel papel da disfunção autonômica cardiaca na morte súbita associada à doença de Chagas. Arq Bras Cardiol. 1991;56(6):429-34.

12. Ramos SG, Matturri L, Rossi L, Rossi MA. Lesions of mediastinal paraganglia in chronic chagasic cardiomyopathy: cause of sudden death? Am Heart J. 1996;131(2):417-20.

13. Baroldi G, Oliveira SJ, Silver MD. Sudden and unexpected death in clinically silent” Chagas’disease: a hypothesis. Int J Cardiol. 1997;58(3):263-8.

14. Junqueira LF Jr. A summary perspective on the clinical-functional significance of cardiac autonomic dysfunction in Chaga’s disease. Rev Soc Bras Med Trop. 2006;39 Suppl 3:64-9.

15. Porto CC. O eletrocardiograma no prognóstico e evolução da doença de Chagas. Arq Bras Cardiol. 1964;17:313-46.

16. Brasil A. Evolução e prognóstico da doença de Chagas. Arq Bras Cardiol. 1965;18(5):365-80.

17. Acquatella H, Catalioti F, Gomez-Mancebo JR, Davalos V, Villalobos L. Long-term control of Chaga’s disease in Venezuela: effects on serologic findings, electrocardiographic abnormalities, and clinical outcome. Circulation. 1987;76(3):556-62.

18. Sousa AC, Marin-Neto JA, Maciel BC, Gallo L Jr, Amorim DS. Cardiac parasympathetic impairment in gastrointestinal Chagas’ disease. Lancet. 1987;1(8539):985.

19. Marin-Neto JA, Bromberg-Marin G, Pazin Filho A, Simões MV, Maciel BC. Cardiac autonomic impairment and early myocardial damage involving the right ventricle are independent phenomena in Chagas’ disease. Int J Cardiol. 1998;65(3):261-9.

20. Primeira reunião de pesquisa aplicada em Doença de Chagas. Validade do conceito de forma indeterminada de doença de Chagas. Rev Soc Bras Med Trop. 1985;18:46.

21. Fortin J, Haitchi G, Bojiic A, Habenbacher W, Grullenberger R, Heller A, et al. Validation and verification of the Task Force Monitor. Results of Clinical Studies for FDA 510(k) No: K014063, August 2001. [Cited on 02 Jun 2008]. Available from: http://www.mendeley.com/catalog/validation-verification-task-force-monitor/

22. Penaz J, Voigt A, Teichmann W. Contribution to the continuous indirect blood pressure measurement. Z Gesamte Inn Med. 1976;31(24):1030-3.

References

and accompanies the disease evolution, being more intense in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with ventricular function, but with the density and complexity of spontaneous ventricular arrhythmias.

Clinical implicationsWe believe that BRS analysis, a simple low-cost methodology,

can be clinically used to identify, among chagasic patients with the arrhythmogenic form and preserved ventricular function, those at higher risk to develop potentially malignant arrhythmias, and, thus, to guide earlier interventions.

Study limitationBecause of the small sample size, prospective studies,

involving a greater number of patients, should be conducted to confirm the results.

Author contributionsConception and design of the research: Santos AM,

Scanavacca MI, Darrieux F, Ianni B, Melo SL, Santos Neto F,

Sosa E, Hachul DT; Acquisition of data: Santos AM, Ianni B, Santos Neto F, Hachul DT; Analysis and interpretation of the data: Santos AM, Scanavacca MI, Darrieux F, Melo SL, Pisani C, Hachul DT; Statistical analysis: Santos AM, Scanavacca MI, Pisani C, Hachul DT; Writing of the manuscript: Santos AM, Santos Neto F, Hachul DT; Critical revision of the manuscript for intellectual content: Santos AM, Scanavacca MI, Darrieux F, Ianni B, Melo SL, Pisani C, Santos Neto F, Sosa E, Hachul DT.



Sources of Funding


Study Association

This article is part of the thesis of Doctoral submitted by Astrid Rocha Meireles Santos, from FMUSP-Incor.

585

Original Article


Arq Bras Cardiol. 2014; 102(6):579-587

23. Wesseling KH. Finger arterial pressure measurement with Finapres. Z Kardiol. 1996;85 Suppl 3:38-44.

24. Parlow J, Viale JP, Annat G, Hugson R, Quintin L. Spontaneous cardiac baroreflex in humans: comparasion with drugs – induced responses. Hypertension. 1995;25(5):1058-68.

25. La Rovere MT, Mortara A, Schwartz PJ. Baroreflex sensitivity. J Cardiovasc Electrophysiol. 1995;6(9):761-74.

26. Teichholz LE, Kreuler T, Herman MV, Gorlin R. Problems in Echocardiographic volume determinations: echocardiographic-angiographic correlation in the presence or absence of assynergy. Am J Cardiol. 1976;37(1):7-11.

27. Rassi A Jr, Rassi SG, Rassi A. Sudden death in Chagas’ disease. Arq Bras Cardiol. 2001;76(1):75-96.

28. Schwartz PJ, Stone HL. The role of the autonomic nervous system in sudden coronary death. Ann N Y Acad Sci. 1982;382:162-80.

29. Mendonza I, Moleiro F, Marques J. Morte súbita na doença de Chagas. Arq Bras Cardiol. 1992;59(1):3-4.

30. La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ. Baroreflex sensitivity and heart variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes after Myocardial Infarction). Investigators. Lancet. 1998;351(9101):478-84.

31. La Rovere MT, Specchia G, Mortara A, Schwartz PJ. Baroreflex sensitivity, clinical correlates, and cardiovascular mortality among patients with a first myocardial infarction: a prospective study. Circulation. 1988;78(4):816-24.

32. Junqueira Júnior LF, Gallo Júnior L, Manço JC, Marin Neto JA, Amorim DS. Subtle cardiac autonomic impairment in Chaga’s disease detected by baroreflex sensitivity testing. Braz J Med Biol Res. 1985;8(2):171-8.

33. Jessus PC. Avaliação da função autonômica do coração utilizando a variabilidade da freqüencia cardiaca, nos dominios do tempo e da freqüencia, na forma indeterminada da doença de Chagas. [Tese]. São Paulo: Faculdade de Medicina da Universidade de São Paulo; 2000.

34. Villar JC, Léon H, Morillo CA. Cardiovascular autonomic function testing in asymptomatic T. cruzi carriers: a sensitive method to identify subclinical Chagas disease. Int J Cardiol. 2004;93(2-3):189-95.

35. Parati G, Di Rienzo M, Bertiniere G, Pomidossi G, Casadei R, Groppelli A, et al. Evaluation of the baroreceptor-heart rate reflex by 24-hour intra-arterial blood pressure monitoring in humans. Hypertension. 1988;12(2):214-22.

36. Robbe HW, Mulder LJ, Ruddel H, Langewitz WA, Veldman JB, Mulder G. Assessment of baroreceptor reflex sensitivity by means of spectral analysis. Hypertension. 1987;10(5):538-43.

37. Lucini D, Guzzetti S, Casiraghi S, Pagani M. Correlation between baroreflex gain and 24-h indices of heart rate variability. J Hypertens. 2002;20(8):1625-31.

38. Rassi A Jr, Rassi A, Little WC, Xavier SS, Rassi SG, Rassi AG, et al. Development and validation of a risk score for predicting death in Chaga’s heart disease. N Engl J Med. 2006;355(8):799-808.

39. The Cardiac Arrhythmia Pilot Study. The CAPS Investigators. Am J Cardiol. 1986;57(1):91-5.

586

Original Article


Arq Bras Cardiol. 2014; 102(6):579-587587

Original Article

Tai Chi Chuan for Cardiac Rehabilitation in Patients with Coronary Arterial DiseaseRosane Maria Nery1,2, Maurice Zanini1,2, Juliana Nery Ferrari1,2, César Augusto Silva1, Leonardo Fontanive Farias1, João Carlos Comel1,2, Karlyse Claudino Belli1,2, Anderson Donelli da Silveira1-3, Antonio Cardoso Santos2, Ricardo Stein1-3

Hospital de Clínicas de Porto Alegre1, Porto Alegre; Universidade Federal do Rio Grande do Sul (UFRGS)2, Porto Alegre; Vitta Centro de Bem-Estar Físico3, Porto Alegre, RS – Brazil

Mailing Address: Ricardo Stein •Grupo de Pesquisa em Cardiologia do Exercicio (CardioEx); Serviço de Cardiologia - Hospital de Clinicas de Porto Alegre - Rua Ramiro Barcelos, 2.350, sala 2061. Postal Code 90035-007, Porto Alegre, RS - BrazilE-mail: [email protected] received August 29, 2013; revised manuscript October 16, 2013; accepted October 16, 2013.

DOI: 10.5935/abc.20140049

Abstract

Background: Several studies have shown that Tai Chi Chuan can improve cardiac function in patients with heart disease.

Objective: To conduct a systematic review of the literature to assess the effects of Tai Chi Chuan on cardiac rehabilitation for patients with coronary artery disease.

Methods: We performed a search for studies published in English, Portuguese and Spanish in the following databases: MEDLINE, EMBASE, LILACS and Cochrane Register of Controlled Trials. Data were extracted in a standardized manner by three independent investigators, who were responsible for assessing the methodological quality of the manuscripts.

Results: The initial search found 201 studies that, after review of titles and abstracts, resulted in a selection of 12 manuscripts. They were fully analyzed and of these, nine were excluded. As a final result, three randomized controlled trials remained. The studies analyzed in this systematic review included patients with a confirmed diagnosis of coronary artery disease, all were clinically stable and able to exercise. The three experiments had a control group that practiced structured exercise training or received counseling for exercise. Follow-up ranged from 2 to 12 months.

Conclusion: Preliminary evidence suggests that Tai Chi Chuan can be an unconventional form of cardiac rehabilitation, being an adjunctive therapy in the treatment of patients with stable coronary artery disease. However, the methodological quality of the included articles and the small sample sizes clearly indicate that new randomized controlled trials are needed in this regard. (Arq Bras Cardiol. 2014; 102(6):588-592)

Keywords: Coronary Artery Disease / rehabilitation; Tai Ji; Exercise.

IntroductionIn Brazil , cardiovascular diseases, in particular

coronary arterial disease (CAD), are one of the major causes of morbidity/mortality and are responsible for a significant share of costs associated with hospitalizations in the Sistema Único de Saúde (National Health System) and pharmacological management1-3. In this context, nonpharmacological approaches such as l i festyle modifications and regular practice of physical exercise have been investigated with the aim of offering patients better treatment and decreasing the overall cost for the Brazilian healthcare system3,4. Patients who undergo exercise-based therapy are likely to exhibit an improvement in several aspects of cardiopulmonary function, which optimizes

the balance between oxygen supply and demand in the ischemic myocardium5-11.

Some oriental exercises deserve special attention because they are accessible, inexpensive, and can be performed within the community12. Of the various techniques available, we highlight Tai Chi Chuan (TCC), an ancient Chinese martial art that includes low to moderate intensity traditional aerobic exercises13. This practice essentially involves learning a sequence of movements that can vary according to different styles. Most preliminary exercises include circular displacements with circular and spiral body movements. The sequence is nothing more than a basis for detailed work on the body and mind12. In China, TCC has been used for centuries as an exercise for people of various age groups; it is very popular among the elderly14. Individuals practice TCC primarily to develop mind–body interaction, breathing and movement control, eye–hand coordination, and a peaceful state of mind. With the aging of the world population and increasing healthcare costs, the interest toward TCC has increased, and it is now used for the management of chronic diseases of various etiologies14-18.

The present study aimed to conduct a systematic review of the literature on studies that examine TCC as a modality for cardiac rehabilitation and raise questions for future research on the use of TCC in CAD patients.

588

Original Article

Nery et al.Tai Chi Chuan na reabilitação cardíaca

Arq Bras Cardiol. 2014; 102(6):588-592

Methods

Eligibility criteriaRandomized clinical trials (RCT) published in English,

Spanish, and Portuguese that reported on TCC training in patients aged > 18 years with confirmed CAD were included. It was necessary to include a control group that practiced any type of structured physical exercise (aerobic, resistance, or a combination of both) and/or received counseling for physical exercise.

Structured physical exercise was defined as an intervention wherein patients were engaged in a planned program with individualized exercises under the supervision of qualified professionals. Counseling for physical exercise was defined as an intervention wherein the patients, although not involved or partially involved in supervised physical training, received formal instructions to perform regular exercise with or without individualized prescription.

Exclusion criteriaStudies that examined cardiovascular outcomes in healthy

individuals, RCTs conducted in patients with stroke, duplicated publications or substudies of the included studies, and studies with a follow-up duration of < 8 weeks were excluded.

Search strategy and study selectionWe searched the electronic databases MEDLINE

(accessed via PubMed), EMBASE, LILACS, and Cochrane Controlled Trials Register (Cochrane CENTRAL) without data restriction. In addition, we assessed the references cited in the included studies. The literature search was conducted in July 2012, and the review of articles was performed in triplicate by independent investigators. The search strategy via MEDLINE included the following terms: [“Ischemic heart disease”(Mesh) OR “Ischemia, Myocardial” OR “Ischemias, Myocardial” OR “Myocardial Ischemias” OR “Ischemic Heart Disease” OR “Heart Disease, Ischemic” OR “Disease, Ischemic Heart” OR “Diseases, Ischemic Heart” OR “Heart Diseases, Ischemic” OR “Ischemic Heart Diseases”] OR [“Coronary disease”(Mesh) OR “Coronary Diseases” OR “Disease, Coronary” OR “Diseases, Coronary” OR “Coronary Heart Disease” OR “Coronary Heart Diseases” OR “Disease, Coronary Heart” OR “Diseases, Coronary Heart” OR “Heart Disease, Coronary” OR “Heart Diseases, Coronary”] AND [“Tai ji”(Mesh) OR “Tai-ji” OR “Tai Chi” OR “Chi, Tai” OR “Tai Ji Quan” OR “Ji Quan, Tai” OR “Quan, Tai Ji” OR “Taiji” OR “Taijiquan” OR “T'ai Chi” OR “Tai Chi Chuan”].

First, a reference database was created and duplicates were excluded. Subsequently, three independent investigators (CAS, LFF, and JNF) reviewed the titles and abstracts. Abstracts that did not meet the eligibility criteria were excluded, and the full text of Abstracts that did not provide sufficient information about inclusion and exclusion criteria was reviewed. In a second stage, the same reviewers assessed and selected the full texts, blinded to each other’s review. Differences among the reviewers were solved by consensus.

Data extraction and quality assessmentThe three reviewers used the same standardized forms

to independently perform data extraction. We collected data referring to the studies’ methodological characteristics, interventions, and outcomes (maximum or peak oxygen consumption, arterial pressure, and heart rate); the differences were solved by consensus.

Assessment of the risk of biasThe quality of the studies in terms of randomization was

assessed independently as follows: blinding of the patients and evaluators of outcomes regarding allocation, analysis of intention-to-treat, and report of losses or exclusions. The authors’ description of the analysis of intention-to-treat was assumed as a criterion for assurance that both baseline and final evaluations used the same number of patients, excluding those who were lost or eliminated from the study. Studies that did not describe an analysis of intention-to-treat, those that did not describe the total number of patients at the end of the study, and those in which the number of patients at the beginning and end was not the same were considered to not meet this criterion. The methodological quality of each study was assessed using the Cochrane Handbook19. (Table 1).

Results

Description of the studiesOur search resulted in 201 abstracts with language

restrictions (English, Portuguese, and Spanish). After the titles and abstracts were reviewed, a total of 12 articles met the eligibility criteria and were completely analyzed (Figure 1). Of these 12 articles, nine were excluded: three that did not mention the use of randomization in patient allocation, two in which the control group did not receive guidance with regard to physical exercise, one that was a systematic review, one that was a report of preliminary data, and two that did not provide the full text of the article (one only had the abstract, and we could not buy it or contact the authors). Therefore, three studies were included in this systematic review. The latter included samples of patients diagnosed with ischemic disease who were clinically stable and able to exercise (Table 2). The follow-up duration varied between 2 and 12 months.

Risk of biasOf the studies included in the systematic review, 100%

were randomized. None of them described the blinding of allocation, blinding of patients and researchers, or blinding of the evaluators of outcomes in detail. None of the studies made explicit use of the intention-to-treat principle in their statistical analyses.

Effects of interventionsIn the first clinical trial, Channer et al20 randomized patients

with acute myocardial infarction into a group that practiced TCC, a group that practiced conventional aerobic exercise, and a control group that was given health and relaxation advice. After 2 months, the TCC and aerobic exercise groups

589

Original Article


Arq Bras Cardiol. 2014; 102(6):588-592

Figure 1 – Study selection flowchart.

Titles identified in electronic database and

selected n = 201

Excluded n = 9- 3 with inadequate description of randomization- in 2 the control group did not receive guidance on physical exercise- 1 systematic review- 1 report of preliminary data- 2 full texts not available

Studies included in the analysis n = 3

Excludedn = 189 without inclusion criteria

Full-text articles analyzed

n = 12

Table 1 – Criteria for the evaluation of the methodological quality adapted from the Cochrane handbook

StudyThe study mentions

randomization in the text

Generation of the sequence of randomization

Blinding of allocation

Blinding of the participants and

personal evaluations

Blinding of the evaluation of

results

The evaluation of results of

incomplete dataSelected publications

Channer et al20 A NC NC NC NC I I

Sato et al21 A NC NC NC NC NC A

Liu et al22 A NC NC I NC A A

A, adequate; NC, not clear; I, inadequate

exhibited a decreased systolic arterial pressure. Patients in the TCC group, in addition to a decrease in resting heart rate after exercise, exhibited greater adherence to the training sessions. There was no comparison between groups.

In the study by Sato et al21, the randomized subjects in the TCC group exhibited a significant increase in baroreflex sensitivity after 12 months of follow-up, whereas those in the control group did not. The results were adjusted for age, gender, ejection fraction, and body mass index. Changes in the parameters of heart rate variability did not exhibit differences between the groups.

The third RCT included in this review assessed outcomes related to the patients’ functional capacity. After 3 months of follow-up, the participants in the TCC group exhibited an

increase in the chair stand test score and one-leg stand test time and were faster than individuals in the control group in the 8-foot up-and-go test. In addition, the TCC group exhibited increased flexibility and an increased number of repetitions in the step test22.

Discussion

Summary of the evidence The results of this systematic review suggest that the use

of TCC as an exercise and cardiac rehabilitation strategy can have beneficial effects in CAD patients. However, evidence from the western literature is limited, and the studies lack methodological rigor as well as more relevant outcomes.

590

Original Article


Arq Bras Cardiol. 2014; 102(6):588-592

Table 2 – Studies that compared Tai Chi Chuan to structured physical training or counseling for physical activity in patients with ischemic cardiac disease

Study Total number of individuals (men/women) Age (years) Main diagnosis Intervention/control Duration

(months)Mean Delta in the Tai Chi

Chuan group

Channer et al20 126 (90/36) 56 (39– 80) Acute myocardial infarction

Tai Chi Chuan, aerobic exercise,

Health and relaxation education group

2

Heart rate: +2 bpmSystolic arterial pressure:

−3 mmHgDiastolic arterial pressure:

−2 mmHg

Sato et al21 20 (13/7) 68 ± 4 Coronary arterial disease

Tai Chi ChuanUsual care group with

physical activity counseling12

Peak oxygen consumption: +0.1 L.min−1

Heart rate: −4 bpmSystolic arterial pressure:

−6 mmHgBaroreflex sensitivity: +2,2 ms/mmHg; variability in heart rate Low frequency: −16 ms2 High

frequency: +18 ms2

Liu et al22 30 (18/12) NA Post-event or heart surgery

Tai Chi ChuanCardiac rehabilitation group 3

Chair stand: +3 repetitionsSit and stand test: +3 repetitions

Step test: +29 repetitions8-foot up-and-go: -−1 sOne-leg stand: +29 s

NA: not available.

Positive aspectsThis systematic review had some strengths. First, it was a

focused review. Second, it was based on a comprehensive and systematic bibliographic search. Third, it employed methodology that used explicit and reproducible eligibility criteria. Lastly, it was conducted in collaboration with a multidisciplinary team of researchers (physicians, physiotherapists, and physical exercise counselors).

Limitations This systematic review also has some limitations. Because

most of the results reported were positive, the possibility of publication bias cannot be ruled out. Moreover, we observed that these RCTs were methodologically limited by a certain degree of measurement bias because there was no reference to blinding (patients, therapists, and evaluators) or confidentiality regarding blinding of allocation. Finally, our search was restricted to studies published in English, Spanish, and Portuguese. It is possible that articles on TCC as a form of CAD rehabilitation have been published in Mandarin or in other languages.

ConclusionsThis review analyzed the literature on the beneficial use

of TCC, a nonconventional therapy, for the rehabilitation of patients with CAD through a systematic search of various electronic databases. However, the methodological quality of the included articles and the small size of the samples indicate a clear need for new randomized clinical trials on this subject.

It is worth noting that, because of the small number of studies published in this area of knowledge and the limited variety of outcomes, it was not possible to conduct a systematic review with a meta-analysis.

Author contributionsConception and design of the research: Nery RM, Stein R;

Acquisition of data: Nery RM, Zanini M, Ferrari JN, Silva CA, Farias LF, Comel JC; Analysis and interpretation of the data: Nery RM, Zanini M, Ferrari JN, Silva CA, Farias LF, Comel JC, Belli KC, Silveira AD; Statistical analysis: Nery RM, Zanini M, Belli KC; Obtaining financing: Nery RM; Writing of the manuscript: Nery RM, Zanini M, Belli KC, Silveira AD, Santos AC, Stein R; Critical revision of the manuscript for intellectual content: Nery RM, Zanini M, Ferrari JN, Silva CA, Farias LF, Comel JC, Belli KC, Silveira AD, Santos AC, Stein R.


reported.

Sources of FundingThis study was funded by FIPE - HCPA - CNPq.Ricardo Stein is Level 2 CNPq investigator.

Study AssociationThis article is part of the thesis of Doctoral submitted by Rosane

Maria Nery from Universidade Federal do Rio Grande do Sul.

591

Original Article


Arq Bras Cardiol. 2014; 102(6):588-592

1. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010;121(7):948-54.

2. Szwarcwald CL, Viacava F, Vasconcellos MT, Leal MC, Azevedo LO, Queiroz RS, et al. Pesquisa mundial de saúde 2003. Radis/FiOCRUZ. 2004;23:14-33.

3. Ribeiro RA, Mello RG, Melchior R, Dill JC, Hohmann CB, Lucchese AM, et al. [Annual cost of ischemic heart disease in Brazil. Public and private perspective]. Arq Bras Cardiol. 2005;85(1):3-8.

4. Yeh GY, Wang C, Wayne PM, Phillips R. Tai chi exercise for patients with cardiovascular conditions and risk factors: a systematic review. J Cardiopulm Rehabil Prev. 2009;29(3):152-60.

5. Piegas LS, Feitosa G, Mattos LA, Nicolau JC, Rossi Neto JM, Timerman A, et al; Sociedade Brasileira de Cardiologia. Diretriz da Sociedade Brasileira de Cardiologia sobre tratamento do infarto agudo do miocárdio com supradesnivel do segmento ST. Arq Bras Cardiol. 2009;93(6 supl.2):e179-264.

6. Franklin BA, Kahn JK. Delayed progression or regression of coronary atherosclerosis with intensive risk factor modification: effects of diet, drugs, and exercise. Sports Med. 1996;22(5):306-20.

7. Oldridge N. Exercise-based cardiac rehabilitation in patients with coronary heart disease: meta-analysis outcomes revisited. Future Cardiol. 2012;8(5):729-51.

8. Briffa TG, Eckermann SD, Griffiths AD, Harris PJ, Heath MR, Freedman SB, et al. Cost-effectiveness of rehabilitation after an acute coronary event: a randomised controlled trial. Med J Aust. 2005;183(9):450-5.

9. Yeh GY, Wood MJ, Lorell BH, Stevenson LW, Eisenberg DM, Wayne PM, et al. Effects of tai chi mind-body movement therapy on functional status and exercise capacity in patients with chronic heart failure: a randomized controlled trial. Am J Med. 2004;117(8):541-8.

10. O’Connor GT, Buring JE, Yusuf S, Goldhaber SZ, Olmstead EM, Paffenbarger RS, et al. An overview of randomized trials of rehabilitation with exercise after myocardial infarction. Circulation. 1989;80(2):234-44.

11. Lu WA, Kuo CD. The effect of Tai Chi Chuan on the autonomic nervous modulation in older persons. Med Sci Sports Exerc. 2003;35(12):1972-6.

12. Lan C, Lai JS, Chen SY. Tai Chi Chuan: an ancient wisdom on exercise and health promotion. Sports Med. 2002;32(4):217-24.

13. Hong Y, Li JX, Robinson PD. Balance control, flexibility, and cardiorespiratory fitness among older Tai Chi practitioners. Br J Sports Med. 2000;34(1):29-34.

14. Li F, Harmer P, Glasgow R, Mack KA, Sleet D, Fisher KJ, et al. Translation of an effective tai chi intervention into a community-based falls-prevention program. Am J Public Health. 2008;98(7):1195-8.

15. Zeeuwe PE, Verhagen AP, Bierma-Zeinstra SM, Van Rossum E, Faber MJ, Koes BW. The effect of Tai Chi Chuan in reducing falls among elderly people: design of a randomized clinical trial in the Netherlands [ISRCTN98840266]. BMC Geriatr. 2006;6:6.

16. Mustian KM, Palesh OG, Flecksteiner SA. Tai Chi Chuan for breast cancer survivors. Med Sport Sci. 2008;52:209-17.

17. Tsang T, Orr R, Lam P, Comino EJ, Singh MF. Health benefits of Tai Chi for older patients with type 2 diabetes: the “Move it For Diabetes Study”--a randomized controlled trial. Clin Interv Aging. 2007;2(3):429-39.

18. Fransen M, Nairn L, Winstanley J, Lam P, Edmonds J. Physical activity for osteoarthritis management: a randomized controlled clinical trial evaluating hydrotherapy or tai chi classes. Arthritis Rheum. 2007;57(3):407-14.

19. Cochrane handbook for systematic reviews of interventions. 4.2.6. [Cited in 2012 Nov 11]. Disponivel em: http://www.cochrane.org/training/cochrane-handbook.

20. Channer KS, Barrow D, Barrow R, Osborne M, Ives G. Changes in haemodynamic parameters following tai chi chuan and aerobic exercise in patients recovering from acute myocardial infarction. Postgrad Med J. 1996;72(848):349-51.

21. Sato S, Makita S, Uchida R, Ishihara S, Masuda M. Effect of Tai Chi training on baroreflex sensitivity and heart rate variability in patients with coronary heart disease. Int Heart J. 2010;51(4):238-41.

22. Liu J, Li B, Shnider R. Effects of tai chi training on improving physical function in patients with coronary heart disease. J Exerc Sci Fit. 2010;8(2):78-84.

References

592

Original Article

Teaching Basic Life Support to Students of Public and Private High SchoolsJosé Maria Gonçalves Fernandes1,2, Amanda Lira dos Santos Leite1, Bruna de Sá Duarte Auto1, José Elson Gama de Lima2, Ivan Romero Rivera1,2, Maria Alayde Mendonça1,2

Faculdade de Medicina da Universidade Federal de Alagoas1, Hospital Universitário Professor Alberto Antunes - Universidade Federal de Alagoas2, Maceió, AL - Brazil

Mailing Address: José Maria Gonçalves Fernandes •Universidade Federal de Alagoas, Faculdade de Medicina - Av. Lourival Melo Mota, s/n, Cidade Universitária. Postal Code: 57072-900, Maceió, AL - BrazilE-mail: [email protected] received September 13, 2013; manuscript revised December 2, 2013; accepted January 17, 2014

DOI: 10.5935/abc.20140071

Abstract

Background: Despite being recommended as a compulsory part of the school curriculum, the teaching of basic life support (BLS) has yet to be implemented in high schools in most countries.

Objectives: To compare prior knowledge and degree of immediate and delayed learning between students of one public and one private high school after these students received BLS training.

Methods: Thirty students from each school initially answered a questionnaire on cardiopulmonary resuscitation (CPR) and use of the automated external defibrillator (AED). They then received theoretical-practical BLS training, after which they were given two theory assessments: one immediately after the course and the other six months later.

Results: The overall success rates in the prior, immediate, and delayed assessments were significantly different between groups, with better performance shown overall by private school students than by public school students: 42% ± 14% vs. 30.2% ± 12.2%, p = 0.001; 86% ± 7.8% vs. 62.4% ± 19.6%, p < 0.001; and 65% ± 12.4% vs. 45.6% ± 16%, p < 0.001, respectively. The total odds ratio of the questions showed that the private school students performed the best on all three assessments, respectively: 1.66 (CI95% 1.26–2.18), p < 0.001; 3.56 (CI95% 2.57–4.93), p < 0.001; and 2.21 (CI95% 1.69–2.89), p < 0.001.

Conclusions: Before training, most students had insufficient knowledge about CPR and AED; after BLS training a significant immediate and delayed improvement in learning was observed in students, especially in private school students. (Arq Bras Cardiol. 2014; 102(6):593-601)

Keywords: Cardiopulmonary Resuscitation; Education; Basic Life Support; High School Students.

IntroductionAlthough the potential beneficial effect of cardiopulmonary

resuscitation (CPR) has been well established, less than one in three victims of out-of-hospital witnessed cardiopulmonary arrest (CPA) receive lifesaving help from a bystander1. In Brazil, it is estimated that approximately 200,000 CPAs occur annually, with half of the cases occurring out-of-hospital environment2. In 2004, the American Heart Association (AHA) recommended that American schools establish a goal to train all teachers and students in CPR3, in agreement with the guidelines of the International Liaison Committee on Resuscitation (ILCOR), which a year earlier strongly recommended the inclusion of Basic Life Support (BLS) in the school curriculum4,5.

Since then, many U.S. states and some European countries have included the teaching of BLS into the curriculum of high-school students and use of automated external defibrillator (AED)4, as did Norway, which since the beginning of the sixties has established the compulsorily teaching of CPR to schoolchildren6.

Schools are ideal laboratories to teach the population about basic techniques that comprise BLS7, considering that adolescents are usually able to perform chest compressions with the same efficacy as adults8 and are usually present at the scene of a medical emergency, such as homes, malls, airports, stadiums etc.5; in Brazil, approximately 8.4 million students are enrolled in high school and of these, 86% study in public schools9.

However, there is no current legislation that guarantees compulsory BLS training in schools or studies comparing the performance of students in CPR between public and private schools. On the other hand, to produce indicators of education and assist education managers in the evaluation of quality, equity and efficiency of teaching and learning, it is necessary to measure and compare the performance and the skills developed by the students10. Thus, the aim of this study was to evaluate and compare the prior knowledge and the degree of immediate and delayed learning among

593

Original Article

Fernandes et al.BLS for High School Students

Arq Bras Cardiol. 2014; 102(6):593-601

high-school juniors attending one public and one private high school, after training in BLS and use the automated external defibrillator (AED).

MethodsThe present is a longitudinal, prospective study, carried

out in one public and one private school, both in the city of Maceió, state of Alagoas, Brazil. These schools were chosen because they had a significant number of participants in the National High School Exams (ENEM) of 2009 and rank among the best in their respective categories. Inclusion criteria were: to be enrolled in the junior year of high school in the selected school; to be chosen by the school coordinator to participate in the project and sign, along with parents or tutors, the free and informed consent form. Exclusion criteria were: students who had had training in CPR and those who could not attend all activities.

The data collection tool was a questionnaire with 15 multiple-choice questions on general knowledge of basic life support distributed as follows: three questions related to the identification of a CPA; four questions regarding the correct sequence of CPR maneuvers; two questions related to compression/ventilation; three questions related to the management of the AED and three questions related to knowledge about CPR and sudden death. Each correct answer was worth 1 point and, therefore, 15 points (the maximum possible score) corresponded to a success rate of 100%.

First, the students answered the questionnaire. After that, they received theoretical and practical training lasting 180 minutes, given by two medical students according to the following sequence: theoretical background of BLS, chain of survival, correct CPR performance with emphasis on chest compressions, AED use and correct positioning of the victim after recovery in accordance with the international scientific consensus of 201011,12. On the same day, and immediately after the theoretical-practical session, the students were reassessed through the same questionnaire. Six months after the course was administered and without previous knowledge of the students regarding the scheduling, the medical students returned to the schools and reapplied the same questionnaire. The same material was used in both schools for practical activities: two adult CPR training manikins (CPR-80CA - Simulacare); disposable masks for mouth-to-mouth breathing and an automated external defibrillator for training (AED Trainer - Cmos Drake). The project was approved by the Ethics Committee in Research of the Federal University of Alagoas, under N. 005604/2011-54.

Statistical MethodsCategorical variables were compared using Fisher’s exact test.

Continuous variables were expressed as percentages and mean ± standard deviation (for normal distribution) or median with 25th and 75th percentiles (for non-normal distribution), tested for normality using D'Agostino-Pearson omnibus test and analyzed with Student’s t test or nonparametric Mann-Whitney test.

To identify possible differences in learning among students from the same school, analysis of variance (ANOVA) for repeated measures (followed by Tukey's test) or Kruskal-Wallis

test for non-normally distributed data were used. The total odds ratio (OR) and the OR of each question with 95% confidence intervals (95%CI) was calculated to compare the differences in prior knowledge and learning between students of the two schools. Statistical significance was considered as a p value < 0.05 or when the 95%CI of the odds ratio excluded the value 1.

Sample size was calculated at 19 students for each school, considering a significance level of 0.05 (two-tailed) and a statistical power of 85% to detect a 20% difference in learning, based on the results of the ENEM 2009, which showed a mean difference between the two schools of 24% with an estimated standard deviation of 20%13. Considering the risk of nonparticipation, the number of students in each school was increased.

ResultsOf the eighty-seven volunteers who initiated the activities,

thirty students from each school (seven males in each group) answered all three questionnaires. Eighteen and nine students from the public and private schools, respectively, refused to participate in the second or third evaluation. The mean age in the public school was slightly older than in the private school: 16.8 ± 0.70 years vs. 16.5 ± 0.68 (p = 0.04). Both schools showed no significant differences regarding gender (p = 1.0).

The rates of correct answers of public school students in the prior, immediate and at six months after training were, respectively, 30.2% ± 12.2% (95% CI: 25.7% to 34.8%); 62.4% ± 19.6% (95% CI: 55.1% to 69.8%) and 45.6% ± 16% (95% CI: 39.6% to 51.5%). When compared, these rates were significantly different (Figure 1). On the other hand, the rates of correct answers of private school students in the prior, immediate and at six months after training were, respectively, 42% ± 14% (95% CI: 36.5% to 47%); 86% ± 7.8% (95% CI: 82.6% to 88.5%) and 65% ± 12.4% (95% CI: 60.2% to 69.5%). When compared, these rates were also significantly different (Figure 2).

After, the questions related to the identification of CPA, the correct sequence of CPR maneuvers, the compression/ventilation ratio and AED management were grouped and analyzed, they showed a significant overall increase in knowledge after training with satisfactory late retention of learning among students from both schools (Tables 1 and 2).

Public School vs. Private SchoolThe rates of correct answers among the public school

students were significantly lower than those of private schools in the three assessments, as shown in Figure 3. Table 3 shows the odds ratios for the fifteen questions in the three moments between students of the two schools. In the prior evaluation, the private school students showed higher numbers of correct answers in most questions, although only one of them showed statistical significance; after the training, this trend persisted and the private school students were significantly better in 7 and 8 of the fifteen questions, respectively, at the immediate and delayed evaluations.

594

Original Article


Arq Bras Cardiol. 2014; 102(6):593-601

Figure 1 – Means of correct answers with 95% confidence intervals in the prior, immediate and late evaluations among public school students.

When the grouped questions were compared, the private school students showed, in the immediate evaluation, significantly higher number of correct answers related to the recognition of the CPA, the correct CPR sequence and AED management (Figure 4); at the late evaluation, this superiority was markedly repeated for the questions concerning CPR maneuvers and compression/ventilation ratio; however, there were significant only for the latter (Figure 5).

Both schools, after the training, obtained rate increases that exceeded 100% of correct answers when compared to baseline knowledge in the immediate evaluation (p < 0.001). After six months of training, such increase was still statistically significant compared to baseline knowledge: 53% for the public school and 55% for the private school (p < 0.001), demonstrating satisfactory increase and retention of knowledge by the students (Figure 3).

DiscussionThis study showed that students in the junior year of high

school from public and private high schools showed high rates of learning immediately after receiving the course on basic life support, as well as a satisfactory level of proficiency when evaluated six months after the training, especially the private school students, which had a significantly higher performance in the three evaluations in relation to the public school students.

Studies comparing BLS teaching among students of public and private high schools are scarce. Parnell et al14 assessed the knowledge and attitudes regarding resuscitation of high school students in New Zealand and found slightly higher rates of knowledge among private school students when compared to public school students, although both had low awareness of CPR principles. This was, however, a cross-sectional study in which a single questionnaire was applied to a mixed population of students trained and not previously trained in CPR.

Miró et al7, in a longitudinal study, assessing the influence of several factors associated with learning in students from high schools in Barcelona, Spain, observed satisfactory levels of immediately learning and after one year of training in CPR, respectively, 58% and 42%, with significantly better results for students from private schools. However, in this study, approximately 44% of the students had already participated in first-aid courses or were unable to inform that and, after a multivariate analysis, they found no independent association between private school teaching with performance and knowledge retention.

There is substantial evidence that retention of BLS knowledge and skills for its application rapidly decline after the initial training15. Several authors have studied this issue, but there is no consensus in the literature regarding the optimal time interval between trainings, which can vary according to

595

Original Article


Arq Bras Cardiol. 2014; 102(6):593-601

Figure 2 – Means of correct answers with 95% confidence intervals in the prior, immediate and late evaluations among private school students.

Table 2 – Rates of correct answers given by Private School students to grouped questions

Grouped questions Prior Evaluation Immediate Evaluation Delayed Evaluation p (ANOVA / Kruskal- Wallis)

CPA – Identification (%) 28.8 ± 23 80 ± 24 46 ± 30 < 0.001

CPR – Maneuvers (%) 38 ± 27 100 (67 – 100) 67 (33 – 100) < 0.001

Compression/Ventilation ratio (%) 50 (0 – 50) 100 (100 -100) 100 (50 – 100)* < 0.001

AED – Management (%) 43 ± 32 84 ± 19 69 ± 17 < 0.001

Data expressed as mean ± standard deviation or median and 25-75th interquartile range. *p > 0.05 vs. immediate evaluation. CPA: Cardiopulmonary arrest; CPR: Cardiopulmonary resuscitation; AED: Automated external defibrillator.

Table 1 – Rates of correct answers given by Public School students to grouped questions

Grouped Questions Prior Evaluation Immediate Evaluation Delayed Evaluation p (ANOVA / Kruskal- Wallis)

CPA - Identification (%) 31 ± 23 59 ± 27 40 ± 28* < 0,001

CPR - Maneuvers (%) 19 ± 19 47 ± 21 47 ± 32† < 0,001

Compression/Ventilation ratio (%) 25 ± 34 100 (50 – 100) 48 ± 31 < 0,001

AED - Management (%) 34 ± 28 67 ± 28 62 ± 29† < 0,001

Data expressed as mean ± standard deviation or median and 25-75th interquartile range. *p > 0.05 vs. Prior Evaluation; †p > 0.05 vs. Immediate evaluation. CPA: Cardiopulmonary arrest; CPR: Cardiopulmonary resuscitation; AED: Automated external defibrillator.

596

Original Article


Arq Bras Cardiol. 2014; 102(6):593-601

Figure 3 – Comparison of means of correct answers with 95% confidence intervals in the prior, immediate and late evaluations among students from public and private schools.

Table 3 – Odds ratio (OR) between the private and public schools with their respective 95% confidence intervals (95% CI) for the fifteen questions in the prior, immediate and delayed evaluations

QuestionsPrior Evaluation Immediate Evaluation Delayed Evaluation

OR (95%CI) p OR (95%CI) p OR (95%CI) p

1 2.10 (0.71 to 6.22) 0.28 1.00 (0.36 to 2.75) 1.00 3.76 (1.04 to 13.7) 0.07

2 1.64 (0.53 to 5.12) 0.57 1.64 (0.53 to 5.12) 0.57 1.00 (0.34 to 2.93) 1.00

3 0.35 (0.10 to 1.16) 0.14 8.11 (1.61 to 40.8) 0.010 1.00 (0.36 to 2.76) 1.00

4 0.14 (0.02 to 1.23) 0.10 1.30 (0.31 to 5.40) 1.0 7.86 (1.96 to 31.7) 0.003

5 2.36 (0.63 to 8.92) 0.33 36.0 (8.10 to 160) 0.0001 3.50 (1.11 to 11.0) 0.05

6 2.51 (0.83 to 7.64) 0.17 50.1 (5.97 to 420) 0.0001 53.6 (3.00 to 957) < 0.001

7 3.06 (0.97 to 9.66) 0.09 2.07 (0.18 to 24.2) 1.00 0.38 (0.13 to 1.09) 0.12

8 2.29 (0.80 to 6.50) 0.19 7.00 (1.38 to 35.5) 0.02 4.03 (1.37 to 11.9) 0.012

9 1.16 (0.40 to 3.35) 1.00 2.67 (0.92 to 7.70) 0.11 1.96 (0.70 to 5.48) 0.30

10 2.33 (0.81 to 6.73) 0.19 10.5 (1.23 to 90.7) 0.03 5.23 (1.66 to 16.5) 0.007

11 1.31 (0.47 to 3.60) 0.80 7.25 (0.82 to 64.5) 0.10 12.3 (2.46 to 60.9) < 0.001

12 0.86 (0.29 to 2.55) 1.00 1.96 (0.70 to 5.48) 0.30 0.55 (0.18 to 1.62) 0.41

13 18.3 (3.67 to 91.2) < 0.001 7.00 (1.38 to 35.5) 0.02 4.30 (1.41 to 13.1) 0.02

14 1.71 (0.62 to 4.77) 0.44 4.46 (0.47 to 42.5) 0.35 2.67 (0.84 to 8.46) 0.16

15 2.19 (0.72 to 6.70) 0.27 23.0 (1.26 to 420) 0.005 10.4 (0.53 to 201) 0.12

Total 1.66 (1.26 to 2.18) < 0.001 3.56 (2.57 to 4.93) 0.0001 2.21 (1.69 to 2.89) < 0.001

597

Original Article


Arq Bras Cardiol. 2014; 102(6):593-601

Figure 4 – Rates of correct answers of grouped questions given by students from public and private schools at the immediate evaluation.

Figure 5 – Rates of correct answers of grouped questions given by students from public and private schools six months after training.

the characteristics of the instructors, participants and their proportions, quality of theoretical and practical training and the evaluation results at the end of course16. Basic skills, such as asking for help, chest compression and ventilation, decrease three to six months after the training; however, these data are based on heterogeneous studies regarding the course’s duration and design, characteristics of instructors and participants and frequency of participants’ involvement in real resuscitations15,16. Berden et al17, evaluating a group of nurses in noncardiac units, concluded that training every six months was enough to maintain satisfactory CPR skills. Woollard et al18, training laymen from a UK airport, observed that the interval in CPR and AED training should not exceed seven months. Moreover, Riegel et al19, studying lay volunteers, observed a satisfactory degree of retention in CPR and AED, even after 17 months of initial training.

In this study, in relation to general knowledge about CPR, it was observed that the percentage of correct responses in the immediate and late evaluations were significantly higher in the private school group in relation to the public school one; however, in relation to the AED management, public school students showed no significant differences when compared to the private school students in the late evaluation, or significant decrease in learning when assessed six months after the training. Apparently, the learning process with the AED is easier and the skills persist for a longer period than the CPR maneuvers19,20.

This inequality of results unfavorable to the public school may be justified by a number of factors, such as lack of attention or motivation, less access to information, less qualified teachers, lower income, lower maternal education and availability of quality laboratories13,21 and is in agreement

598

Original Article


Arq Bras Cardiol. 2014; 102(6):593-601

with the assessments of the Brazilian Education Development Index (IDEB) and ENEM results, which have successively shown throughout the country a superior performance of private schools students when compared to public school ones12. According to the indicators produced by the National System of Basic Education Assessment (SAEB), 96% of students in the senior year of high school with difficulties in reading and interpreting texts of different literary genres are enrolled in public schools, while 76 % of students with reading skills of more complex argumentative texts study in private schools20.

The insistence in incorporating the teaching of CPR in the school curriculum is based on the fact that children and adolescents trained in CPR are likely to discuss the training with siblings, friends and other family members, raising awareness about BLS and the demand for traditional training courses, which will result in the increase in the number of adults trained in CPR in the community22. The sooner they are trained, the better is the retention rate in formal courses22, and even elementary school students already have sufficient cognitive skills to correctly apply the AED23.

However, there are potential barriers for the introduction of a training program in schools24, particularly those involving cost and time availability in the curriculum; additionally, many students and lay people are not willing to provide care due to fear of infection, shock, legal consequences and risk of harming the victim25. Moreover, the use of AEDs is hindered by the availability of trained staff and lack of familiarity and responsibility with the device26. In the U.S., in 2000, a Federal Law was passed in order to reduce such barriers against the placement and use of AEDs in public areas. Since that time, these devices are already available in many public places such as airports, malls, gyms and public offices5. In Brazil, there is no specific legislation requiring the installation of AEDs in public and private environments.

Some studies that compared the standard theoretical-practical training in BLS with theoretical courses only using videos showed conflicting results27,28. Thus, we chose to use in this study a theoretical-practical approach, performed by medical students who showed to be qualified, motivated, willing to devote time to scientific projects, and who had already successfully participated in several studies on the teaching of CPR29-31.

LimitationsThis study did not use a practical test as an evaluation tool.

Although the written test should not replace the practical test on an individual assessment, it can be a viable alternative as a tool to estimate and compare the efficacy of psychomotor skills, especially in collective training programs32,33. The theoretical evaluation used in this study, although based on multiple-choice questions prepared by the AHA, has not been validated in previous studies. And finally, the fact that students showed a satisfactory acquisition of knowledge during the course does

not necessarily indicate a good performance of psychomotor skills during CPR in the real world32.

ConclusionsTo the best of our knowledge, this is the first study

that identified and directly compared the stages of prior, immediate and delayed knowledge after the theoretical and practical instruction on CPR and AED, among high school students from public and private schools. We observed that students from both schools had inadequate prior knowledge about BLS, but after theoretical and practical training, the students, particularly those from the private school, showed considerable increase in this knowledge with satisfactory persistence of such information, even after six months of training. However, considering the importance of the subject, the universal presence of schools in adolescents' lives and the inevitable decline in the levels of learning, we suggest a definitive incorporation of the BLS teaching as a compulsory subject in the curriculum of public and private high schools in the country.

AcknowledgementsWe thank Professors Roohelmann Pontes Silva, from

Escola Estadual Moreira e Silva and Ernesto Stadler and João Thomaz Neto, from Colégio Contato Maceió, for supporting this project, as well as the students of the participating schools for their commitment to establish new knowledge. We are also grateful to Professor Maria Aparecida Silva and Dr. Fabiana Yulita for the correction and review of the manuscript.

Author contributionsConception and design of the research: Fernandes JMG,

Leite ALS, Auto BSD, Rivera IR, Mendonça MA; Acquisition of data: Leite ALS, Auto BSD; Analysis and interpretation of the data and Writing of the manuscript: Fernandes JMG, Leite ALS, Auto BSD, Lima JEG; Statistical analysis: Fernandes JMG; Critical revision of the manuscript for intellectual content: Fernandes JMG, Rivera IR, Mendonça MA.


reported.


Study AssociationThis study is not associated with any thesis or dissertation work.

599

Original Article


Arq Bras Cardiol. 2014; 102(6):593-601

1. Nichol G, Thomas E, Callaway CW, Hedges J, Powell JL, Aufderheide TP,et al; Resuscitation Outcomes Consortium Investigators. Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA. 2008;300(12):1423-31.Erratum in JAMA. 2008;300(15):1763.

2. Gonzalez MM, Timerman S, de Oliveira RG, Polastri TF, Dallan LA, Araújo S, et al. I diretriz de ressuscitação cardiopulmonar e cuidados cardiovasculares de emergência da sociedade brasileira de cardiologia: resumo executivo. Arq Bras Cardiol. 2013;100(2):105-13.

3. Hazinski MF, Markenson D, Neish S, Gerardi M, Hootman J, Nichol G,et al; American Heart Association; American Academy of Pediatrics; American College of Emergency Physicians; American National Red Cross; National Association of School Nurses; National Association of State EMS Directors; National Association of EMS Physicians; National Association of Emergency Medical Technicians; Program for School Preparedness and Planning; National Center for Disaster Preparedness; Columbia University Mailman School of Public Health Response to cardiac arrest and selected life-threatening medical emergencies: the medical emergency response plan for schools: a statement for healthcare providers, policymakers, school administrators, and community leaders. Circulation. 2004;109(2):278-91.

4. Chamberlain DA, Hazinski MF; European Resuscitation Council; American Heart Association; Heart and Stroke Foundation of Canada; Resuscitation Council of Southern Africa; Australia and New Zealand Resuscitation Council; Consejo Latino-Americano de Resusucitación. Education in resuscitation: an ILCOR symposium: Utstein Abbey: Stavanger, Norway: June 22-24, 2001.Circulation.2003;108(20):2575-94.

5. Cave DM, Aufderheide TP, Beeson J, Ellison A, Gregory A, Hazinski MF, et al; American Heart Association Emergency Cardiovascular Care Committee; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Cardiovascular Diseases in the Young; Council on Cardiovascular Nursing; Council on Clinical Cardiology, and Advocacy Coordinating Committee. Importance and implementation of training in cardiopulmonary resuscitation and automated external defibrillation in schools: a science advisory from the American Heart Association. Circulation. 2011;123(6):691-706.

6. Lind B, Stovner J. Mouth-to-mouth resuscitation in Norway. JAMA. 1963;185:933-5.

7. Miró O, Escalada X, Jiménez-Fábrega X, Díaz N, Sanclemente G, Gomez X, et al. Programa de Reanimación Cardiopulmonary Orientado a Centros de Enseñanza Secundaria (PROCES): conclusiones trás 5 años de experiência. Emergencias. 2008;20:229-36.

8. Jones I, Whitfield R, Colquhoun M, Chamberlain D, Vetter N, Newcombe R.At what age can schoolchildren provide effective chest compressions? An observational study from the Heartstart UK schools training programme. BMJ. 2007;334(7605):1201.

9. Portal Brasil. Educação: Brasil em números. [Acesso em 2013 jun 13]. Disponível em: http://www.brasil.gov.br/educacao

10. Instituto Nacional de Estudos e Pesquisas Educacionais. (INEP). Anísio Teixeira. Qualidade da educação: uma nova leitura do desempenho dos estudantes de 3ª Serie do ensino médio; 2004. [Acesso em 2013 jun 13]. Disponível em: http://www.inep.gov.br

11. Koster RW, Baubin MA, Bossaert LL, Caballero A, Cassan P, Castrén M, et al. European Resuscitation Council Guidelines for Resuscitation 2010. Section 2. Adult basic life support and use of automated external defibrillators. Resuscitation. 2010;81(10):1277-92.

12. Hazinski MF, Nolan JP, Billi JE, Böttiger BW, Bossaert L, de Caen AR, et al. Part 1: Executive summary: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Circulation.2010;122(16 Suppl 2):S250-75.

13. Instituto Nacional de Estudos e Pesquisas Educacionais Anisio Teixeira.. (INEP). [Acesso em 2013 jun 13]. Disponível em: http://www.inep.gov.br.

14. Parnell MM, Pearson J, Galletly DC, Larsen PD. Knowledge of and attitudes towards resuscitation in New Zealand high-school students. Emerg Med J. 2006;23(12):899-902.

15. Bhanji F, Mancini ME, Sinz E, Rodgers DL, McNeil MA, Hoadley TA, et al. Part 16: education, implementation, and teams: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18 Suppl3):S920-33.

16. Soar J, Monsieurs KG, Ballance JH, Barelli A, Biarante D, Greif R, et al European Resuscitation Council Guidelines for Resuscitation 2010 Section 9. Principles of education in resuscitation. Resuscitation. 2010;81(10):1434-44.

17. Berden HJ, Hendrick JM, Willems FF, Pijls NH, Knape JT. How frequently should basic cardiopulmonary resuscitation training be repeated to maintain adequate skills? BMJ. 1993;306(6892):1576-77.

18. Woollard M, Whitfield R, Newcombe RG, Colquhoun M, Vetter N, Chamberlain D. Optimal refresher training intervals for AED and CPR skills: a randomised controlled trial. Resuscitation. 2006;71(2):237-47.

19. Riegel B, Nafziger SD, McBurnie MA, Powell J, Ledingham R, Selvia R, et al. How well are cardiopulmonary resuscitation and automated external defibrillator skills retained over time? Results from the Public Access Defibrillation (PAD) Trial. Acad Emerg Med. 2006;13(3):254-63.

20. Gundry JW, Comess KA, DeRook FA, Jorgenson D, Bardy GH. Comparison of naive sixth-grade children with trained professionals in the use of an automated external defibrillator. Circulation. 1999;100(16):1703-7.

21. Sampaio B, Guimarães J. Diferenças de eficiência entre ensino público e privado no Brasil. Economia Aplicada. 2009;13(1):45-68.

22. Roppolo LP, Pepe PE: Retention, retention, retention: targeting the young in CPR skills training! Crit Care. 2009;13(5):185.

23. Lawson L, March J: Automated external defibrillation by very young, untrained children. Prehosp Emerg Care. 2002;6(3):295-8.

24. Mosesso VN. AEDs in schools: lessons learned and to be learned. Resuscitation. 2013;84(4):401-2.

25. Hubble MW, Bachman M, Price R, Martin N, Huie D. Willingness of high school students to perform cardiopulmonary resuscitation and automated external defibrillation. Prehosp Emerg Care. 2003;7(2):219-24.

26. Mercer CW, Rhodes LA, Phillips JR. Automated external defibrillators in West Virginia schools. WV Med J. 2012;108(4):18-24.

27. Isbye DL, Rasmussen LS, Lippert FK, Rudolph SF, Ringsted CV. Laypersons may learn basic life support in 24min using a personal resuscitation manikin. Resuscitation. 2006;69(3):435-42.

28. Miotto HC, Camargos FR, Ribeiro CV, Goulart EM, Moreira MC. Effects of the use of theoretical versus theoretical-practical training on cardiopulmonary resuscitation. Arq Bras Cardiol. 2010;95(3):328-31.

29. Connolly M, Toner P, Connolly D, McCluskey DR. The ‘ABC for life’ programme Teaching basic life support in schools. Resuscitation. 2007;72(2):270-9.

30. Breckwoldt J, Beetz D, Schnitzer L, Waskow C, Arntz HR, Weimann J. Medical students teaching basic life support to school children as a required element of medical education: a randomised controlled study comparing three different approaches to fifth year medical training in emergency medicine. Resuscitation. 2007;74(1):158-65.

31. Ribeiro LG, Germano R, Menezes PL, Schmidt A, Pazin-Filho A. Medical students teaching cardiopulmonary resuscitation to middle school Brazilian students. Arq Bras Cardiol. 2013;101(4):328-35.

32. Remmen R, Scherpbier A, Denekens J, Derese A, Hermann I , Hoogenboom R, et al. Correlation of a written test of skills and a performance based test: a study in two traditional medical schools. Med Teach. 2001;23(1):29-32.

33. Kramer AW, Jansen JJ, Zuithoff P, Düsman H, Tan LH, Grol RP, et al. Predictive validity of a written knowledge test of skills for an OSCE in postgraduate training for general practice. Med Educ. 2002;36(9):812-9.

References

600

Original Article


Arq Bras Cardiol. 2014; 102(6):593-601601

Review Article

Clinical and Echocardiographic Predictors of Mortality in Chagasic Cardiomyopathy - Systematic ReviewClodoval de Barros Pereira Júnior1, Brivaldo Markman Filho2

Laboratory of Echocardiography and Chagas Disease Outpatient Clinic of Pronto-Socorro Cardiológico de Pernambuco (PROCAPE) – Universidade de Pernambuco1, Recife, PE; Hospital das Clínicas da Universidade Federal de Pernambuco2, Recife, PE - Brazil

AbstractDiagnosis, prognosis and evaluation of death risk in Chagas

cardiomyopathy still constitute a challenge due to the diversity of manifestations, which determine the importance of using echocardiography, tissue Doppler and biomarkers.

To evaluate, within a systematic review, clinical and echocardiographic profiles of patients with chronic chagasic cardiomyopathy, which may be related to worse prognosis and major mortality risk.

To perform the systematic review, we used Medline (via PubMed), LILACS and SciELO databases to identify 82 articles published from 1991 to 2012, with the following descriptors: echocardiography, mortality and Chagas disease. We selected 31 original articles, involving diagnostic and prognostic methods.

The importance of Chagas disease has increased due to its emergence in Europe and United States, but most evidence came from Brazil. Among the predictors of worse prognosis and higher mortality risk are morphological and functional alterations in the left and right ventricles, evaluated by conventional echocardiography and tissue Doppler, as well as the increase in brain natriuretic peptide and troponin I concentrations. Recently, the evaluations of dyssynchrony, dysautonomia, as well as strain, strain rate and myocardial twisting were added to the diagnostic arsenal for the early differentiation of Chagas cardiomyopathy.

Developments in imaging and biochemical diagnostic procedures have enabled more detailed cardiac evaluations, which demonstrate the early involvement of both ventricles, allowing a more accurate assessment of the mortality risk in Chagas disease.

IntroductionChagas disease remains a serious worldwide, economic

and public health problem, endemic in South America and emergent in Europe and the United States1. The World

KeywordsChagas Cardiomyopathy / mortality; Prognosis; Chagas’

Disease; Echocardiography.Mailing Address: Brivaldo Markman Filho •Avenida Visconde de Jequitinhonha, 2544/1902, Boa Viagem. Postal Code: 51130-020, Recife, PE - BrazilE-mail: [email protected] , [email protected] Manuscript received June 23, 2013; revised manuscript September 08, 2013; accepted September 16, 2013.

DOI: 10.5935/abc.20140068

Health Organization (WHO), in 2013, estimated between 7 and 8 million people chronically infected with Trypanosoma cruzi in the world, most of them in 21 Latin American countries, among which more than 30% develop cardiac abnormalities and more than 10% digestive and neurological problems2. Additionally, the WHO estimated there are 25 million people at risk of contracting the disease3.

In Brazil, it is estimated that there are somewhere between 2 to 3 million infected individuals4, which makes it the third main cause of parasitic diseases after malaria and schistosomiasis, and the fourth cause of great damage among communicable diseases in America3.

In the acute phase of Chagas disease, cardiac involvement can occur in up to 90% of cases5. After six to eight weeks, most patients show recovery of the clinical picture6.

In the indeterminate phase, the infestation is only diagnosed by serological or parasitological tests, as there is no evidence of organ damage. Subclinical cardiac involvement may be demonstrated by imaging studies in some patients7. Symptoms will develop in the chronic phase, a long time after the first infestation, with cardiac involvement being mainly responsible for the reduction in life expectancy7.

Several physiopathological hypotheses have been implicated in myocardial damage, ranging from direct aggression by the parasite1,8, sympathetic and parasympathetic dysautonomia9 and coronary microvascular abnormalities9 to autoimmune processes10. The lack of definition of the physiopathology complicates the diagnosis and hence, the early implementation of treatment in patients with Chagas cardiomyopathy11. For these reasons, and because the mortality from Chagas cardiomyopathy is closely related to significant organ involvement, it becomes important to identify prognostic markers related to worse outcomes12.

This article aims to systematically review the clinical and echocardiographic profiles of patients with chronic Chagas’ disease, which may be related to worse prognosis and mortality.

MethodA systematic literature review was performed in the

following databases: Medical Literature Analysis and Retrieval System Online (MEDLINE) via PubMed, Latin American and Caribbean Literature on Health Sciences (LILACS) and Scientific Electronic Library Online (SciELO). Using the descriptors: echocardiography, Chagas disease and mortality, the following were employed as inclusion criteria for the studies: being original; having as research subjects individuals diagnosed with Chagas disease; addressing diagnostic or prognostic methods

602

Review Article

Pereira Júnior & Markman FilhoPredictors in Chagasic Cardiomyopathy

Arq Bras Cardiol. 2014; 102(6):602-610

Figure 1 – Flow chart of the number of articles found and selected after applying the inclusion and exclusion criteria

Articles retrieved by the search strategyN = 82

Items excluded after reading the titleN = 13

Items excluded after reading the abstractN = 14

Items excluded after reading the full textN = 23

Articles selected for the reviewN = 31

Items selected for reading of the full textN = 55

Repeat articlesN = 1

Items selected for reading of the abstractN = 69

of Chagas cardiomyopathy: detailing clear inclusion, exclusion and discontinuation (when relevant) criteria, and objectives for the research subjects, regardless of gender.

The search was not limited by period of time and language. Duplicate articles, those assessing interventions, those performed in patients aged zero to 10 years and in animals, in vitro experiments, case reports and editorials were excluded.

Data Analysis Article selection was performed in three steps. Firstly, the

titles were read and the ones that did not fit any of the study inclusion criteria were excluded. Secondly, summaries of the selected studies in the first step were read and, likewise, the ones that did not fit at least one of the inclusion criteria were excluded. In the third step, all studies that were not excluded in previous studies were read in full to select the ones that would be included in this review.

A total of 52 articles were found in the MedLine database via PubMed using the descriptors, of which 13 were excluded after reading the title and eight after reading

the abstracts. The remaining 31 articles were read in full and 12 were excluded and 19 included in the review. A total of 30 articles were located in the SciELO and LILACS databases, six of which were excluded after reading the abstracts and 11, after reading the full article; one of these was a duplicate, resulting in the selection of 12 articles. Thus, 31 articles were included in this review, published between 1991 and 2012 (Figure 1).

For a better presentation of the results, we chose to classify methodologically articles selected by the variables: author, year, country, sample size, mean age of the subjects, presence of criteria for subject selection (inclusion and exclusion), of comparison group and results (Chart 1).

ResultsRegarding temporal distribution, there was a marked

prevalence of publications in the past decade, with only two publications having been published in the penultimate decade (1990-1999) 13-14. Another important point to be considered is the absolute hegemony of studies carried out in Brazil (77%

603

Review Article


Arq Bras Cardiol. 2014; 102(6):602-610

Chart 1 – Methodological classification of selected articles

Author Year Country Type of study

N. of patients

Mean age (years) (range)

Selection criteria

Group of comparison Results

Guerrero et al.13 1991 Venezuela Cohort 269 > 18 Yes Yes

The higher prevalence of complex ventricular arrhythmias in chronic Chagasic patients, compared to those with primary dilated

cardiomyopathy, exposes Chagasic patients to a worse prognosis.

Marin-Neto et al.14 1998 Brazil Prospective 45

With digestive tract abnormalities =

39.4 ± 10.7Without abnormalities =

42.4 ± 11.9

Yes Yes

Dysautonomia is evident in chagasic patients with the digestive form, but not with the indeterminate form. There is no causal association with early myocardial damage, apparent only in patients with impaired right

ventricular function, which appears to be the mechanism for the predominance of

systemic over pulmonary congestion when heart failure occurs.

Barros et al.15 2001 Brazil Prospective 40 Not informed Yes Yes

TDI allowed the identification of higher isovolumic contraction of the septal wall in

chagasic patients with the indeterminate form.

Barros et al.16 2002 Brazil Prospective 30 39.9 ± 9.9 Yes Yes

TDI allows early identification of the RV dysfunction (increased isovolumic contraction

of the septal and lateral walls).

Barros et al.17 2003 Brazil Prospective

cross-sectional 77

Control: 35.8 ± 10.6

Chagasic com normal ECG: 40.7 ± 8.5

Chagasic with abnormal ECG: 43.9 ± 11.1

Yes Yes Tissue Doppler imaging (TDI) identifies early contractility abnormalities.

Arias et al.18 2003 Brazil Prospective cross-sectional 60 > 18 Yes Yes

Troponin levels are elevated in different clinical presentations of Chagas’ disease and

detect early inflammation.

Nunes et al.19 2004 Brazil Prospective

cross-sectional 74 47.5 ± 12.9 (22-73) Yes No

RV dysfunction was significantly associated with LV involvement and pulmonary

hypertension, which was more correlated with RV overload than to contractility.

Viotti et al.20 2004 Argentina Cohort 849 > 18 Yes NoEchocardiography determines the prognosis

of chronic Chagasic patients without congestive heart failure (CHF).

Talvani et al.21 2004 Brazil Prospective

cross-sectional 81 43.5 ± 11.1 Yes Yes

High levels of brain natriuretic peptide (BNP) in Chagasic patients detect heart failure (HF) or severe HF manifestations,

generating arrhythmias.

Rocha et al.22 2004 Brazil Cohort 60 47 ± 13 Yes No Left atrial volume (LAV) was an important

predictor of death in Chagas disease.

Freitas et al.23 2005 Brazil Cohort 1220 13 ± 72 (45) Yes No Chagasic etiology in HF patients was the

main prognostic factor for mortality.

Melo et al.24 2005 Brazil Transversal 2562.7 ± 7.7 chronic

42.2 ± 11.7 asymptomatic

YesYes (Chagas

asymptomatic x symptomatic)

BNP increases with worsening functional class and cardiac area.

Pazin-Filho et al.25 2006 Brazil Prospective

cross-sectional 59 37-76> 55 Yes No

In time, slight alterations in the left ventricular ejection fraction (LVEF) lead to the worsening

of global LV systolic function.

Rassi Jr et al.26 2006 Brazil Cohort 424 47 ± 11 Yes Yes Development of death risk assessment in

chagasic cardiomyopathy based on six factors

Chaves et al.27 2006 Colombia Prospective

cross-sectional 430 Md = 40.5 (IQR = 36-45) Yes Yes

Comparing controls, stage I and stage II using tissue Doppler, it is possible to

identify, in stage II, the greater relaxation time, lower velocity of A wave, higher E/A ratio, lower pulmonary A velocity, greater pulmonary/mitral A velocity ratio, greater

annulus A wave velocity, and the RV shows increased tricuspid A wave velocity and

isovolumic contraction time.

604

Review Article


Arq Bras Cardiol. 2014; 102(6):602-610

Continuation

Benchimol Barbosa28 2007 Brazil Cohort 50 34-74 Yes No

In the male gender, pathological Q wave, ventricular extrasystoles,

ventricular tachycardia and abnormal echocardiogram (diastolic and systolic dysfunction and apical aneurysm) are

markers of poorer prognosis.

Barbosa et al.29 2007 Brazil Prospective

cross-sectional 59 48 ± 11 Yes No

The pro-BNP levels remained a strong correlation with LVEF and duration indices of diastolic dysfunction of left atrial volume, as well as with the more severe forms of the

disease, allowing their differentiation from the moderate forms.

Nunes et al.30 2008 Brazil Cohort 158 48 ± 12 Yes No

Evaluation of systolic and diastolic function using the Tei index (myocardial performance

index) and CF showed to be useful prognostic tool in Chagasic cardiomyopathy.

Villas-Boas et al.31 2008 Brazil Prospective

cross-sectional 3851.3 ± 1.6 for chagasic

and 53.3 ± 2.3 for control patients

Yes Yes

The concentration of BNP is increased and correlates with heart failure (direct),

functional class (direct) natremia (reverse), blood pressure (reverse), right atrial

pressure, R/L ventricular dysfunction, TNF-alpha (demonstrating inflammatory

characteristic of the disease).

Nunes et al.32 2009 Brazil Cohort 192 48 ± 12 Yes No

LAV provides powerful information to predict mortality regardless of clinical and

echocardiographic data.

Del Castillo et al.33 2009 Brazil Prospective

cross-sectional 40 55 ± 10 Yes Yes

Based on the principle of speckle tracking and employing the assessment of intramyocardial velocity gradients, they identified the reduction

in the percentage of deformation (X-strain) and the rate of deformation (strain rate) of the

infero-lateral left ventricular wall in Chagas patients unidentifiable by clinical data or

conventional echocardiography.

Terzi et al.34 2010 Brazil Prospective cross-sectional 62 58 Yes No

Chagasic patients with normal LVEF and normal electrocardiogram had a significant frequency of contractile alterations related

with arrhythmias and reduced LVEF.

Pereira Nunes et al.35

2010 Brazil Cohort 287

Chagasic: 48.3 ± 12 Idiopathic:

49.6 ± 15.9

Yes YesIdentification of Chagasic etiology resulted in poor prognosis in patients with HF, regardless

of clinical and echocardiography data.

Nunes et al.36 2010 Brazil Cohort 65 48.6 ± 9.1 Yes No

RV dysfunction is an important determinant, regardless of exercise capacity, and the systolic valvular velocity of this ventricle

was associated with the peak volume of O2 consumed, regardless of age, gender and

echocardiographic parameters.

Garcia-Alvarez et al.37

2010 Spain Cohort 54 20-58 (mean 37) Yes Yes (4 groups)

The identification of diastolic dysfunction can be achieved by increasing BNP, which

correlates with functional class (NYHA), TNF-alpha, PS, endothelin, ANP and

reduction in the percentage of longitudinal and radial deformation to assess contractility.

Duarte et al.38 2011 Brazil Cohort 56 56 ± 10 Yes No

Although high prevalence of intraventricular dyssynchrony and

moderate interventricular dyssynchrony was demonstrated among Chagasic

patients, especially in patients without a pacemaker, dyssynchrony did not show to

be a risk factor for poor prognosis.

Valerio et al.39 2011 Spain Descriptive 100 38.2 ± 10.2 Yes No

The fact that Spain has become a center of migration of Latin Americans in Europe

has aroused the concern of Chagas disease becoming an important cause of

cardiomyopathy in health services.

605

Review Article


Arq Bras Cardiol. 2014; 102(6):602-610

of those included in this review)4,6-9,11,12,14-19,21-26,28-36,38,40-43. Among the five studies performed in other countries, three were carried out in Latin America13,20,27 and two in Europe37,39.

Regarding the use of comparison groups, it was observed that in 18 articles (58%) the authors used the design of comparisons between groups8,13-18,21,24,26,27,31,35,37 ,33,40-41, 43. It is also interesting to note the predominance of adult patients in the selected studies, with only one study including adolescent chagasic patients23.

As for the addressed topics, 10 articles considered prognostic factors of mortality and risk of disease progression using echocardiography13,19,22,23,26,28,30,32,35,36, five studies assessed left ventricular ejection fraction (LVEF)20,25,29,34,39, alone or together with prognostic factors, seven articles assessed systolic and diastolic ventricular function with tissue Doppler15-17,27,33,36,40, five assessed concentrations of brain natriuretic peptide (BNP)21,24,29,31,37, one study assessed the prognostic value of troponin concentrations18, one study evaluated ventricular dyssynchrony38, two studies assessed cardiac dysautonomia14,41, two studies used two-dimensional echocardiography to assess ventricular deformation (strain, strain rate and twisting)33,42 and one study addressed the proinflammatory and prothrombotic factors in Chagas disease 43.

DiscussionThe predominance of publications over the last ten years

may be related to the fact that in past decades, the prognosis for Chagas disease relied almost exclusively on clinical predictors of mortality, which could be evaluated solely during patient follow-up. This means that the preventive

process was restricted to the tertiary level, when treatment aimed only to improve quality of life, as the entire spectrum of cardiomyopathy was already established 7. With the technological development of ultrasound devices, which allow performing more detailed tests capable of providing valuable information on the physiopathology and prognosis of Chagas cardiomyopathy and establish hemodynamic correlation, studies have become more comprehensive.

As for the near hegemony of studies performed in South America, particularly in Brazil, one possible explanation is that our country constitutes a true source of specialized centers and researchers who, for decades, have been devoted to research on Chagas disease, mainly concerning the factors that alone or combined, may be involved with worse prognosis and increased mortality. Among these are Rassi Jr et al.26, Nunes et al. 19,30,32,35,36,40, Marin-Neto et al. 14 Barbosa 28, Barbosa et al.29.

Another possible explanation for the increase in publications in the last decade was the dissemination of T. cruzi beyond the limits of Central and South America. The immigration of Latin Americans resulted in the diagnosis of patients with the indeterminate form, who were blood donors, especially in Europe39, arousing concerns given the frequency at which Chagas cardiomyopathy became an important diagnostic issue in health services, which were not used to managing these patients39.

This concern is also found in other countries, especially with the objective of providing primary and secondary disease prevention26.

Studies with group comparison13-18,21,24,26,27,31,33,35,37,40,41 aimed to evaluate the clinical, hemodynamic and evolution

Continuation

Nunes et al.40 2012 Brazil Prospective

endpoint 232 48 ± 12 Yes Yes (survivors and deaths)

Using tissue Doppler imaging, they identified risk factors for death: functional class III and IV, increased RV Tei, increased left atrial volume

index and interaction of LV ejection fraction and E / E’ index and protectors: E / E ' ratio and

reduction in LV ejection fraction.

Vasconcelos and Junqueira41

2012 Brazil Prospective cross-sectional

15 controls and 13

chagasic

controls = 40-46chagasic = 35-49

Yes Yes

The sympathetic and parasympathetic depressions with preserved balance were associated with heart rate variability and

increased left ventricular systolic diameter in Chagasic patients with cardiomyopathy,

indicating that these depressions may precede and be independently more severe than ventricular dysfunction,

with no causal association between this depression and dysfunction.

Del Castillo et al.42 2012 Brazil Prospective

cross-sectional 20 54.8 ± 13.5 Yes Yes

Employing the speckle tracking technique, it was possible to prove reduction of twisting

and torsional deformation of myocardial fibers in Chagas cardiomyopathy, thus

differentiating it from ventricular hypertrophy.

Melo et al.43 2010 Brazil Cross-sectional 150 G1:51.02 ± 1.256 G2: 54.88 ± 0.8787 Yes Yes

It was demonstrated that both groups had increased inflammatory activity, but there

were no indications of greater prothrombotic status among chagasic patients.

Legend: ANP: Atrial Natriuretic Peptide, BNP: brain natriuretic peptide; DTI: Doppler tissue imaging (Image by tissue Doppler), CF: cardiac function, LVEF, left ventricular ejection fraction, HF: Heart failure; NYHA: New York Heart Association; O2: oxygen; Tei: myocardial performance index, TNF: Tumor Necrosis Factor; LAV: left atrial volume, RV: right ventricle, LV: left ventricle.

606

Review Article


Arq Bras Cardiol. 2014; 102(6):602-610

aspects of Chagas cardiomyopathy, while those aimed to identifying morphological and functional characteristics related to prognosis and mortality did not employ this methodology19,20,22,23,25,28-30,32,34,36,38,39. The identification of the predominance of publications aimed to investigate adult patients (between the third and fourth decades of life), when compared to those involving adolescents, seems justified by the physiopathology of the disease. In the chronic phase, symptoms of organ involvement most often manifests after 10 to 30 years since the first infestation. That is why Chagas cardiomyopathy in adolescents is a rarer event, for which the acute phase is the most frequent in epidemiological studies23. It is appropriate to stress that, in cases of vertical transmission of the disease, children and adolescents may exhibit signs of early cardiac impairment, but these cases have been the subject of underreporting, reinforcing the scarcity of cases also in adolescence23 .

In addition to the involvement of young adults, chronic Chagas cardiomyopathy constitutes a serious public health problem, as it is a major cause of heart failure with a high mortality rate23. This fact, which persists a century after the first description of the disease, has motivated many studies on prognostic factors of mortality and risk of disease progression, among which 10 were included in this review10,17,19,20,23,25, 27,29,31,37. All these studies recognize the importance of identifying the chagasic etiology of heart failure, given its destructive and overwhelming role due to incessant myocarditis, caused by extensive myocardial fibrosis, as well as being responsible for complex ventricular arrhythmias, which may explain poorer prognosis of chagasic patients when compared to patients with primary dilated cardiomyopathy13,34.

Emphasizing the importance of the etiological diagnosis of heart failure in the context of Chagas disease, another study, which compared 224 patients with chagasic cardiomyopathy and 63 with idiopathic dilated cardiomyopathy, showed that only the identification of Chagas disease conferred poor prognosis for patients with heart failure, regardless of clinical and echocardiographic data35.

In addition to heart failure, other studies have shown that right ventricular involvement may be useful for risk stratification of Chagas cardiomyopathy. The myocardial performance index (Tei index), assessed by echocardiography, adds significant prognostic information and allows analysis of systolic and diastolic function of the right ventricle (RV), very useful and effective in patients with Chagas heart disease30. Another index used to evaluate RV systolic function is the tricuspid annular plane systolic excursion (TAPSE), capable of providing more reliable information33.

Thus, the RV morphological and functional characteristics were also the subject of a study including 74 patients19, demonstrating that such changes are associated with significant left ventricular involvement and pulmonary hypertension, contributing to poor prognosis of Chagas disease and also acting as an independent determinant of reduced exercise capacity36. Among the left ventricular alterations, the presence of apical aneurysm, impaired left ventricular function and ventricular extrasystoles also acted as predictors of poor prognosis28, associated with increased left atrial volume, regardless of the clinical data and conventional

echocardiographic parameters20,22,32. Left ventricular wall motion abnormalities in patients with normal systolic function were shown to be a predictor of ventricular function deterioration in chagasic patients with normal ECG and no symptoms or physical signs25 .

The evaluation of several mutually related indices demonstrates their potential in determining prognostic factors of mortality and risk of disease progression27, as emphasized in the paper of Rassi Jr. et al.26, wich described six risk factors and attributed a score to constitute a simple and validated score. It should be noted that this score was gradually increased by the adding of other factors identified by echocardiography and tissue Doppler imaging.

Mitral annular tissue Doppler, an established modality of echocardiographic assessment of ventricular diastolic and systolic function, disclosed early abnormalities of myocardial contractility15-17, thus enabling a previous cardiac planning, regarding the institution of early measures to preserve left ventricular function. It also showed to be effective in predicting RV systolic function, correlated with peak oxygen uptake, regardless of the influence of gender and age or other echocardiographic parameters36. Additionally, the E / E’ ratio showed high prognostic value for mortality in patients with mild or moderate left ventricular dysfunction40. Tissue Doppler imaging constitutes an easy and reproducible way of systolic and diastolic assessment that must be increasingly used, as it is superior to conventional echocardiography17, identifying overall contractile abnormalities, especially in patients at the indeterminate phase of Chagas disease and with normal ECG15.

Other studies have sought to determine the prognostic markers of cardiac function in Chagas disease. Among them, BNP, a neurohormone of specific cardiac origin, has been the subject of five studies, with the aim of associating its concentration to cardiac dysfunction21,24,29,31,37, with discordant results.

Talvani et al.21, by correlating BNP levels to ventricular function indices in chagasic patients, showed that because it was a simple, fast, relatively inexpensive method, it should be used for diagnosis of heart failure in these patients, to identify the increased risk of severe arrhythmias, sudden death and reduced survival.

Additionally, they recommended the use of a cutoff lower than 60 pg/mL to characterize patients with low risk of severe chagasic cardiomyopathy, for which echocardiography was not necessary. A study carried out in 2005, however, despite confirming the correlation between high concentrations of BNP and cardiac involvement in Chagas disease, did not confirm it when considered ejection fraction. This study showed that individuals with the indeterminate form of Chagas disease had serum BNP levels similar to those found in the general population, i.e., it did not contribute to the diagnosis of this clinical form24.

Subsequent studies, however, have supplemented the significance of BNP measurement in patients with Chagas disease and were also compared to those results. They demonstrated that the assessment of systolic and diastolic functions of the left ventricle and right atrial pressure, together with serum BNP levels, helps to stratify the risk of cardiovascular event development, facilitating the diagnosis of Chagas cardiomyopathy21,29,31.

607

Review Article


Arq Bras Cardiol. 2014; 102(6):602-610

Some studies contrasted to the findings of Melo et al.24, by identifying a strong correlation between BNP levels and ejection fraction29, as well as the validity of BNP to identify patients in the indeterminate form of Chagas disease37. The differences between the findings can be attributed to increased sensitivity and specificity of the test used for BNP measurement, verified since 2006, in response to its large-scale use in many countries.

Considering Chagas disease in the context of inflammatory diseases, another biomarker of heart muscle injury has been evaluated in chagasic patients - troponin I. In chagasic individuals, the concentration of troponin I has been identified in the chronic and indeterminate forms, allowing early detection of myocardial inflammation and consequently, secondary prevention of this injury18. More recent studies have sought prognostic markers of myocardial damage degree and, consequently, risk of death, based on physiological processes. In this context, a study has addressed ventricular dyssynchrony38, while another41 sought to update cardiac dysautonomia, of which importance in Chagas disease had already been highlighted in 199814.

As for the dyssynchrony in chagasic cardiomyopathy, a cohort assessed by echocardiography showed high intraventricular and moderate interventricular prevalence and found that, despite the high prevalence, this phenomenon may not affect prognosis as it is independent from the changes in QRS. The importance of this finding is that dyssynchrony, being a segmental alteration secondary to the presence of areas of fibrosis associated with chronic diffuse inflammatory process, does not behave as a risk factor. However, the authors left the significance of dyssynchrony open to discussion and suggested studies with larger samples so that the evaluation of poor prognosis can be supplemented by other factors38.

In 1998, Marin-Neto et al. 14, based on the premise that the digestive form of Chagas disease is characterized by autonomic dysfunction, essential for the development of megaesophagus and megacolon, admitted that this dysfunction could be involved in ventricular alterations of Chagas cardiomyopathy. Cardiac autonomic function was evaluated using angiography with Tc-99m labeled RBCs, demonstrating that patients with the digestive form had pronounced parasympathetic cardiac injury and right ventricular dysfunction in the absence of diagnosed left ventricular dysfunction. However, cardiac autonomic dysfunction was absent in the indeterminate forms, even in the presence of similar right ventricular involvement14. The importance of this pioneering study was to demonstrate the possibility that the presence of severe right ventricular involvement can constitute the only cardiac dysfunction in asymptomatic chronic chagasic patients with no other clinical signs of cardiac involvement14.

Fourteen years later, a period in which echocardiography was improved by the technological development of equipment and programs (software), allowing early evaluation of morphological and functional disorders, cardiac autonomic function in asymptomatic chronic Chagas cardiomyopathy started to be investigated once again in more detail41.

Cardiac autonomic dysfunction, characterized by marked depression of autonomic modulation of heart rate variability

with preserved vagosympathetic balance, was verified regardless of the standing position of the patient. The association of autonomic dysfunction with normality of most ventricular echocardiographic variables suggests that dysautonomia must be a primary phenomenon that may precede ventricular mechanical changes. Thus, its assessment may constitute a precursor of ventricular dysfunction41.

Recently, new echocardiographic tools have been employed to allow earlier diagnosis of ventricular alterations in chagasic patients, as, although echocardiography is considered adequate for analysis of ventricular contractility and regional myocardial function, it does not allow ventricular deformation assessment. Two-dimensional X-strain echocardiography is an easy-to-apply technique that allows differentiating passive from active deformation of the ventricular cavity walls, through the assessment of tangential and longitudinal deformation. Del Castillo et al.33, using X-strain and strain rate determination, showed the presence of significant reduction in the percentage of deformation and the rate of deformation of the infero-lateral left ventricular wall of patients with Chagas disease, especially in the middle and apical portions, regions that show segmental contractility alterations in the cardiac form of Chagas disease.

This study was improved42 with the use of the speckle tracking technique, which allows determination of basal and apical myocardial rotation, as well as the twisting, i.e., the angular difference resulting from the clockwise rotation of the apical region and of the basal in the counterclockwise direction, during ventricular systole. These new echocardiographic parameters were employed42 in the differentiation of chagasic patients and those with left ventricular hypertrophy. By identifying the reduction in global longitudinal strain, radial strain, twisting and myocardial rotation in patients with chagasic cardiomyopathy, as well as the increase in these parameters in ventricular hypertrophy, the authors42 recommend the use of this modality as a differentiation tool.

In addition to the search for new methodologies for cardiac function assessment, the association between inflammatory and prothrombotic activity in Chagasic cardiomyopathy has been investigated in an attempt to better characterize the disease, as to attain better care of these patients43. Such studies are relevant to the elucidation of the damage of chronic Chagas cardiomyopathy, so that it will no longer be included in the group of neglected diseases, considering that after 100 years of its discovery, it is still a serious public health problem. Chronic Chagas disease still leads individuals to heart failure as result of the disease, incapacitating them for work and for life, increasing public expenses, notably with incapacity to lead a productive life, cardio-stimulation (pacemakers, implantable cardioverter-defibrillators and cardiac resynchronizers), drug therapy and heart transplantation.

ConclusionThe evidence shown in this review allows us to state

that the possibility of early etiological diagnosis of chronic chagasic cardiomyopathy has increased over time, enabling us to predict the reduction of mortality in these patients.

608

Review Article


Arq Bras Cardiol. 2014; 102(6):602-610

1. Carod-Artal FJ, Gascon J. Chagas disease and stroke. Lancet Neurol. 2010;9(5):533-42.

2. World Health Organization. (WHO). Chagas disease (American trypanosomiasis). 2013. [Acesso em 2013 abr 4]. Disponivel em: http://www.who.int/mediacentre/factsheets/fs340/en.

3. Completion of national laboratory inventories for wild poliovirus containment: WHO Region of the Americas, March 2010. Wkly Epidemiol Rec. 2010;85(34):329-33.

4. Martins-Melo FR, Alencar CH, Ramos AN Jr, Heukelbach J. Epidemiology of mortality related to Chagas’ disease in Brazil, 1999-2007. PLoS Negl Trop Dis. 2012;6(2):e1508.

5. Ponukollu G, Gowda RM, Khan IA, Navarro VS, Vasavada BC. Clinical aspects of the Chagas’ heart disease. Int J Cardiol. 2007;115(Ponukollu G, Gowda RM, Khan IA, Navarro VS, Vasavada BC 3):279-83.

6. Schmunis GA. Epidemiology of Chagas disease in non-endemic countries: the role of international migration. Mem Inst Oswaldo Cruz. 2007;102 Suppl 1:75-85. Erratum in Mem Inst Oswaldo Cruz. 2007;102(8):2 p following 1009.

7. Biolo A, Ribeiro AL, Clausell N. Chagas cardiomyopathy – where do we stand after a hundred years? Prog Cardiovasc Dis. 2010;52(4):300-16.

8. Marin-Neto JA, Simões MA, Sarabanda AV. Cardiopatia chagásica. Arq Bras Cardiol. 1999;72(3):247-63.

9. Marin-Neto JA, Cunha-Neto E, Maciel BC, Simões MV. Pathogenesis of chronic Chagas heart disease. Circulation. 2007;115(9):1109-23.

10. Yacoub S, Mocumbi AO, Yacoub MH. Neglected tropical cardiomyopathies: I. Chagas disease: myocardial disease. Heart. 2008;94(2):244-8.

11. Abuhab A, Trindade E, Aulicino GB, Fujii S, Bocchi EA, Bacal F. Chagas’ cardiomyopathy: the economic burden of an expensive and neglected disease. Int J Cardiol. 2013;168(3):2375-80.

12. Nunes MC, Barbosa MM. Valor prognóstico da disfunção diastólica em pacientes com miocardiopatia dilatada chagásica. Rev Bras Ecocardiogr. 2004;17(4):15-22.

13. Guerrero L, Carrasco H, Parada H, Molina C, Chuecos R. [Ventricular mechanics and cardiac arrhythmias in patients with chagasic and primary dilated cardiomyopathy. Echo-electrocardiographic follow-up]. Arq Bras Cardiol. 1991;56(6):465-9.

14. Marin-Neto JA, Bromberg-Marin G, Pazin-Filho A, Simões MV, Maciel BC. Cardiac autonomic impairment and early myocardial damage involving the right ventricle are independent phenomena in Chagas’ disease. Int J Cardiol. 1998;65(3):261-9.

15. Barros MV, Rocha MO, Ribeiro AL, Machado FS. Doppler tissue imaging to evaluate early myocardium damage in patients with undetermined form of Chagas’ disease and normal echocardiogram. Echocardiography. 2001;18(2):131-6.

16. Barros MV, Machado FS, Ribeiro AL, Da Costa Rocha MO. Detection of early right ventricular dysfunction in Chagas’ disease using Doppler tissue imaging. J Am Soc Echocardiogr. 2002;15(10 Pt 2):1197-201.

17. Barros MV, Ribeiro AL, Machado FS, Rocha MO. Doppler tissue imaging to assess systolic function in Chagas’ disease. Arq Bras Cardiol. 2003;80(1):36-40.

18. Arias R, Bastos C, Mota G, Sodré F, Moreira A, Tavares A, et al. Troponin in Chagas disease. Braz J Infect Dis. 2003;7(6):358-9.

19. Nunes Mdo C, Barbosa Mde M, Brum VA, Rocha MO. Morphofunctional characteristics of the right ventricle in Chagas’ dilated cardiomyopathy. Int J Cardiol. 2004;94(1):79-85.

20. Viotti RJ, Vigliano C, Laucella S, Lococo B, Petti M, Bertocchi G, et al. Value of echocardiography for diagnosis and prognosis of chronic Chagas disease cardiomyopathy without heart failure. Heart. 2004;90(6):655-60.

21. Talvani A, Rocha MO, Cogan J, Maewal P, de Lemos J, Ribeiro AL, et al. Brain natriuretic peptide and left ventricular dysfunction in chagasic cardiomyopathy. Mem Inst Oswaldo Cruz. 2004;99(6):645-9.

22. Rocha ES, Nunes MC, Rocha MO, Barbosa MM. Volume de átrio esquerdo como preditor de morte em miocardiopatia chagásica dilatada. Rev Bras Ecocardiogr. 2004;17(4):29-36.

23. Freitas HF, Chizzola PR, Paes AT, Lima AC, Mansur AJ. Risk stratification in a Brazilian hospital-based cohort of 1220 outpatients with heart failure: role of Chagas’ heart disease. Int J Cardiol. 2005;102(2):239-47.

24. Melo RB, Parente GB, Victor EG. Determinação do peptidio natriurético cerebral humano em portadores de doença de Chagas. Arq Bras Cardiol. 2005;84(2):137-40.

25. Pazin-Filho A, Romano MM, Almeida-Filho OC, Furuta MS, Viviani LF, Schmidt A, et al. Minor segmental wall motion abnormalities detected in patients with Chagas’ disease have adverse prognostic implications. Braz J Med Biol Res. 2006;39(4):483-7.

References

By demonstrating that ventricular impairment, not only left as it has been emphasized, but also right, occurs since the indeterminate phase of the disease, when symptoms are mild and do not prevent patients from performing activities of daily living, opens up new possibilities that can translate in prolonged life with quality.

New methods of cardiac assessment for the detailing of ventricular impairment, associated with the use of prognostic scores for risk of death in the future tend to be incorporated into cardiologic routine, facilitating the differential diagnosis of Chagas cardiomyopathy while still in its early phase.

Author contributionsConception and design of the research, Acquisition of

data, Analysis and interpretation of the data, Statistical

analysis, Writing of the manuscript and Critical revision of the manuscript for intellectual content: Pereira Júnior CB, Markman Filho B; Obtaining financing: Markman Filho B.


was reported.


Study AssociationThis article is part of the thesis of Master submitted by

Clodoval de Barros Pereira Jr from Universidade Federal de Pernambuco

609

Review Article


Arq Bras Cardiol. 2014; 102(6):602-610

26. Rassi A Jr, Rassi A, Little WC, Xavier SS, Rassi SG, Rassi AG, et al. Development and validation of a risk score for predicting death in Chagas’ heart disease. N Engl J Med. 2006;355(8):799-808.

27. Chaves AM, Villar JC, Luengas CA, Villamizar MC, Hernández L, Celis A, et al. Función diastólica en sujetos con serologia positiva para enfermedad de Chagas procedentes del estudio CHICAMOCHA. Rev Colomb Cardiol. 2006;13(2):79-84.

28. Benchimol Barbosa PR. Noninvasive prognostic markers for cardiac death and ventricular arrhythmia in long-term follow-up of subjects with chronic Chagas’ disease. Braz J Med Biol Res. 2007;40(2):167-78.

29. Barbosa MM, Nunes Mdo C, Ribeiro AL, Barral MM, Rocha MO. N-terminal proBNP levels in patients with Chagas disease: a marker of systolic and diastolic dysfunction of the left ventricle. Eur J Echocardiogr. 2007;8(3):204-12.

30. Nunes Mdo C, Rocha MO, Ribeiro AL, Colosimo EA, Rezende RA, Carmo GA, et al. Right ventricular dysfunction is an independent predictor of survival in patients with dilated chronic Chagas’ cardiomyopathy. Int J Cardiol. 2008;127(3):372-9.

31. Vilas-Boas F, Feitosa GS, Soares MB, Pinho-Filho JA, Nascimento T, Barojas MM, et al. Invasive and noninvasive correlations of B-type natriuretic peptide in patients with heart failure due to Chagas cardiomyopathy. Congest Heart Fail. 2008;14(3):121-6.

32. Nunes MC, Barbosa MM, Ribeiro AL, Colosimo EA, Rocha MO. Left atrial volume provides independent prognostic value in patients with Chagas cardiomyopathy. J Am Soc Echocardiogr. 2009;22(1):82-8.

33. Del Castillo JM, Herszkowicz N, Rego LC, Silva YA, Moro DR, Maia AM, et al. Strain bidimensional do ventriculo esquerdo na forma indeterminada da doença de Chagas. Rev Bras Ecocardiogr Imagem Cardiovasc. 2009;22(1):31-5.

34. Terzi FV, Siqueira Filho AG, Nascimento EM, Pereira Bde B, Pedrosa RC. [Regional left ventricular dysfunction and its association with complex ventricular arrhythmia, in chagasic patients with normal or borderline electrocardiogram]. Rev Soc Bras Med Trop. 2010;43(5):557-61.

35. Pereira Nunes Mdo C, Barbosa MM, Ribeiro AL, Amorim Fenelon LM, Rocha MO. Factores predictivos de la mortalidad en pacientes con miocardiopatia dilatada: importancia de la enfermedad de Chagas como etiologia. Rev Esp Cardiol. 2010;63(7):788-97.

36. Nunes Mdo C, Beloti FR, Lima MM, Barbosa MM, Pinto Filho MM, de Barros MV, et al. Functional capacity and right ventricular function in patients with Chagas heart disease. Eur J Echocardiogr. 2010;11(7):590-5.

37. Garcia-Alvarez A, Sitges M, Pinazo MJ, Regueiro-Cueva A, Posada E, Poyatos S, et al. Chagas cardiomyopathy: the potential of diastolic dysfunction and brain natriuretic peptide in the early identification of cardiac damage. PLoS Negl Trop Dis. 2010;4(9):e826.

38. Duarte Jde O, Magalhães LP, Santana OO, Silva LB, Simões M, Azevedo DO, et al. Prevalence and prognostic value of ventricular dyssynchrony in Chagas cardiomyopathy. Arq Bras Cardiol. 2011;96(4):300-6.

39. Valerio L, Roure S, Sabria M, Balanzo X, Valles X, Seres L. Clinical, electrocardiographic and echocardiographic abnormalities in Latin American migrants with newly diagnosed Chagas disease 2005-2009, Barcelona, Spain. Euro Surveill. 2011;16(38):19971.

40. Nunes MP, Colosimo EA, Reis RC, Barbosa MM, Silva JL, Barbosa F, et al. Different prognostic impact of the tissue Doppler-derived E/e’ ratio on mortality in Chagas cardiomyopathy patients with heart failure. J Heart Lung Transplant. 2012;31(6):634-41.

41. Vasconcelos DF, Junqueira LF Jr. Funções autonômica cardiaca e mecânica ventricular na cardiopatia chagásica crônica assintomática. Arq Bras Cardiol. 2012;98(2):111-9.

42. Del Castillo JM, Silveira CA, Albuquerque ES. Rotação, twisting e torção miocárdica avaliados pela ecocardiografia bidimensional (speckle tracking). Rev Bras Ecocardiogr Imagem Cardiovasc. 2012;25(3):206-13.

43. Melo LM, Souza GE, Valim LR, Moreira FP, Damico EA, Rocha TR, et al. Estudo de fatores pró-trombóticos e pró-inflamatórios na cardiomiopatia chagásica. Arq Bras Cardiol. 2010;95(5):655-62.

610


Angiotensin-converting Enzyme Genetic PolymorphismSomsri Wiwanitkit, Viroj WiwanitkitWiwanitkit House, Bangkhae, Bangkok Tailândia, Hainan Medical University, China

Mailing Address: Somsri Wiwanitkit •Wiwanitkit House, Bangkhae. Postal Code 10160, Bangkok – Thailand.Email: [email protected] received December 3, 2013; revised January 23, 2014; accepted January 23, 2014.

KeywordsPolymorphism, Genetic; Peptidyl-Dipeptidase A.

1. Albuquerque FN, Brandão AA, Silva DA, Mourilhe-Rocha R, Duque GS, Gondar AF, et al. Angiotensin-converting enzyme genetic polymorphism. Arq Bras Cardiol. 2013 Nov 26. [Epub ahead of print].

2. Wiwanitkit V. Angiotensin-converting enzyme gene polymorphism: I and D alleles from some different countries. Clin Appl Thromb Hemost. 2004;10(2):179-82.

3. Yip VL, Pirmohamed M. Expanding role of pharmacogenomics in the management of cardiovascular disorders. Am J Cardiovasc Drugs. 2013;13(3):151-62.

4. Yu Jin, Kuznetsova T, Thijs L, Richart T, Stolarz-Skrzypek K, Yanping Liu, et al. Association of echocardiographic left ventricular structure with the ACE D/I polymorphism: a meta-analysis. J Renin Angiotensin Aldosterone Syst. 2011;12(3):243-53.

References

ReplyIndeed, the sample size limitation is a universal bias in

all of the genetic polymorphisms in heart failure and the ACE-genotype was no different. The metanalysis by Bai et al.1. with 17 different studies included 2.453 cases (i.e. heart failure patients) from all over the world with only 60.3% being white individuals. The author concluded that there was no association between ACE DD genotype and heart failure risk. The different ethnic background of these populations is one of the reasons for the lack of the association and when analyzed individually, some of these studies2,3 did find a relation with ACE genotype and heart failure risks. Even more important is the relationship between the surrogate markers of

disease progression – Echocardiogram parameters – and the genotypes since clinical outcomes will be very hard to prove with the sample size of these populations (which would have to be in thousands not hundreds). Andersson and Sylvén4 for example did find a relationship between echocardiographic parameteres and the ACE genetic polymorphisms. In conclusion, it looks like all these papers combined do not have statistical power to answer in a definitive way the relationship between Heart Failure Prognosis and ACE Genetic Polymorphisms. But it looks like we are on the right track and we will have to proceed with a lot more patients.

DOI: 10.5935/abc.20140077

Sir Editor,The recent report on “angiotensin-converting enzyme

(ACE) genetic polymorphism.” is very interesting. Albuquerque et al.1 concluded that “the DD genotype was independently associated with worse echocardiographic outcome, while the DI genotype, with best echocardiographic profile.” In fact, the polymorphism of ACE is different in different countries and the relationship to clinical disorder is widely mentioned2. The study of ACE polymorphism has proved to be useful in

management of cardiac patients, especially for selection of proper cardiac drug3. However, the relationship to cardiac pathology is still controversial. Similar to the present study, the ventricular function abnormality determined by EKG was proposed for interrelationship with ACE polymorphism by Yu Jin et al4. Nevertheless, the small sample size in the published studies1, 4 is the main obstacle for conclusions. The effect of race in clinical relationship of ACE polymorphism requires a very large study in order to lead to conclusions2.

611


Wiwanitkit et al.Angiotensin-converting enzyme genetic polymorphism

1. Bai Y, Wang L, Hu S, Wei Y. Association of angiotensin-converting enzyme I/D polymorphism with heart failure: a meta-analysis. Mol Cell Biochem. 2012;361(1-2):297-304.

2. Candy GP, Skudicky D, Mueller UK, Woodiwiss AJ, Sliwa K, Luker F, et al. Association of left ventricular systolic performance and cavity size with angiotensin-converting enzyme genotype in idiopathic dilated cardiomyopathy. Am J Cardiol. 1999;83(5):740-4.

3. Raynolds MV, Bristow MR, Bush EW, Abraham WT, Lowes BD, Zisman LS, et al. Angiotensin-converting enzyme DD genotype in patients with ischaemic or idiopathic dilated cardiomyopathy. Lancet. 1993;342(8879):1073-5.

4. Andersson B, Blange I, Sylvén C. Angiotensin-II type 1 receptor gene polymorphism and long-term survival in patients with idiopathic congestive heart failure. Eur J Heart Fail. 1999;1(4):363-9.

References

Arq Bras Cardiol. 2014; 102(6):611-612 612


Assessment of Diastolic Dysfunction: Drugs Could Alter the ResultsEmre Yalcinkaya1, Murat Celik2, Baris Bugan3

Hospital Militar Aksaz - Departamento de Cardiologia1, Mugla, Turquia; Faculdade Militar de Medicina Gulhane - Departamento de Cardiologia2, Ancara, Turquia; Hospital Militar Malatya - Departamento de Cardiologia3, Malatya - Turquia

Mailing Address: Emre Yalcinkaya •Aksaz Military Hospital Department of Cardiology; Aksaz Asker Hastanesi, Kardiyoloji Bolumu, 48750, Aksaz/Marmaris/Mugla - Turkey.Email: [email protected] received December 11, 2013; revised manuscript January 17, 2014; accepted January 17, 2014.

KeywordsStroke volume / drug effects; Ventricular dysfunction; Atrial

function, left; Brazil.

1. El Aouar LM, Meyerfreud D, Magalhães P, Rodrigues SL, Baldo MP, Brasil Y, et al. Relationship between left atrial volume and diastolic dysfunction in 500 Brazilian patients. Arq Bras Cardiol. 2013;101(1):52-8.

2. Mesquita ET, Jorge AJ. Understanding asymptomatic diastolic dysfunction in clinical practice. Arq Bras Cardiol. 2013;100(1):94-101.

3. Biondi B. Mechanisms in endocrinology: Heart failure and thyroid dysfunction. Eur J Endocrinol. 2012;167(5):609-18.

4. Mannheim D, Herrmann J, Bonetti PO, Lavi R, Lerman LO, Lerman A. Simvastatin preserves diastolic function in experimental hypercholesterolemia independently of its lipid lowering effect. Atherosclerosis. 2011;216(2):283-91.

5. Ramirez E, Klett-Mingo M, Ares-Carrasco S, Picatoste B, Ferrarini A, Rupérez FJ, et al. Eplerenone attenuated cardiac steatosis, apoptosis and diastolic dysfunction in experimental type-II diabetes. Cardiovasc Diabetol. 2013;12:172.

References

DOI: 10.5935/abc.20140078

To the Editor,We read with great interest the article by El Aouar et

al.1, entitled “Relationship between left atrial volume and diastolic dysfunction in 500 Brazilian patients”, which was published in the previous issue of Arquivos Brasileiros de Cardiologia. The authors1 aimed to evaluate the relationship between left atrial volume index and different grades of diastolic dysfunction in Brazilian patients submitted to echocardiogram. Although we commend the authors for the detailed and valuable information that they have provided, some comments may be beneficial.

Diastolic dysfunction is associated with adverse outcomes and its prevalence among hypertensive, hyperlipidemic and diabetic adults is very high2. It has been shown that lowering blood pressure and heart rate, management of impaired lipid profile and blood glucose could improve diastolic dysfunction2. Also, thyroid dysfunction has been

associated with the development of diastolic dysfunction even in patients without underlying heart disease3.

Diuretics, ACE inhibitors and angiotension-II receptor antagonists, nitrates and their derivatives, calcium channel blockers, alpha-blockers, nicardipine and phosphodiesterase inhibitors reduce left ventricular filling pressures2,3.

Statins could ameliorate diastolic dysfunction by attenuating myocardial interstitial fibrosis and angiogenesis independently of their lipid lowering effects4.

Thyroid hormonotherapies increase cardiac output by affecting stroke volume and heart rate, and reduce systemic vascular resistance by activating the renin-angiotensin-aldosterone system; resulting in an improvement in diastolic dysfunction3.

It has been demonstrated in diabetic cardiomyopathy that eplerenone, the mineralocorticoid receptor blocker, has anti-fibrotic effects which could attenuate cardiac steatosis, apoptosis and remodelling as well as diastolic dysfunction5.

In conclusion, if the medication details which can be associated with diastolic dysfunction had been given, the study would have been more valuable.

613


Yalcinkaya et al.Assessment of diastolic dysfunction

Response letterWe appreciate your comments in relation to our article.

Left ventricular diastolic function depends on a number of intrinsic and extrinsic factors to the heart. Among intrinsic factors, the most important is the amount and arrangement of collagen deposited in the myocardium. Both the synthesis of the different isoforms of collagen, and the form of deposition of these fibers in myocardial interstice and around the coronary vessels, have an important influence on myocardial relaxation rate which leads, from the hemodynamic point of view, by the fall rate of ventricular pressure during relaxation isovolumetric by transmitral flow rate or by the rate of myocardium movement on mitral annullus. The echocardiogram has been a valuable tool in the assessment of diastolic function and, to the extent that the methods of image become more accessible and improved, and the interest of clinical cardiologists is growing in the accurate measurement of myocardial lusitropism. It is important to note that different types of treatments for heart disease (ACE inhibitors, inhibitors of aldosterone receptors, BRA, etc) or associated clinical conditions, such as hypertension, mellitus diabetes, hypothyroidism, among others, are associated with different degrees of diastolic dysfunction. In this respect the available literature is

extensive. However, the goal of our work was not to explore the pathogenesis of diastolic dysfunction, but rather to focus on two aspects: 1) evaluate the relationship between the volume of VAEi (left atrium indexed by body surface area) and the different degrees of diastolic dysfunction in a number of patients on outpatients treatment with preserved or little reduced systolic function and that were submitted to the transthoracic echocardiography examination in a cardiology diagnostic department; 2) identify clinical and echocardiographic variables independently associated to VAEi increase.

To achieve these goals, the origin and the stage of evolution of diastolic dysfunction are not parameters relevant to the proposed study. However, we consider your comments relevant and they may certainly be used in future substudies within the sample included in our article.

We appreciate the comments made and the interest in our work.

Best regards,Lilia M. Mameri El Aouar.

Author

Arq Bras Cardiol. 2014; 102(6):613-614 614


Case 4 / 2014 – 15-year-old Patient with Atrial Septal Aneurysm, Right Bundle Branch Block and Paroxysmal Atrial FibrillationEdmar AtikClínica privada do Dr Edmar Atik, São Paulo, SP - Brazil

KeywordsAtrial Septal Aneurysm, Atrial; Bundle-branch Block; Atrial

Fibrillation.Mailling Address: Edmar Atik •Rua Dona Adma Jafet, 74, conj.73, Bela Vista. Postal Code 01308-050, São Paulo, SP - BrazilE-mail: [email protected], [email protected] Manuscript received July 23, 2013; revised manuscript July 23, 2013; accepted July 30, 2013.

DOI: 10.5935/abc.20140076

Clinical data: It was reported, one month earlier, that after physical exertion for three hours and at ambient temperature of 42ºC, symptoms of malaise and tachycardia with precordial palpitations arose. At the moment, fibrilo-flutter atrial with 160 bpm heart rate was diagnosed, which was reverted after administering endovenous amiodarone. Initial diagnostic investigation revealed presence of atrial septal defect (ASD) with 16mm diameter and surgical correction was indicated. Overall, the patient was asymptomatic, in full physical and mental activity. No relevant morbid history was reported.

Physical examination: Eupneic, acyanotic, normal pulse. Weight: 45 Kg, Height: 158 cm, BP: 100/65 mmHg, HR: 82 bpm, saturation O2 = 96%. Aorta was not palpable at suprasternal notch.

In the precordium, ictus cordis was not palpable and there were mild systolic impulses on the left sternal border. Heart sounds were normophonetic and mild systolic murmur was auscultated, + of intensity, rough, on the upper left sternal border, without thrill. Liver was not palpable.

Complementary testsElectrocardiogram: (Figure 1) showed sinus rhythm and

Full Right Bundle Branch Block (CRBBB) and Left Bundle Branch Anterior Superior Hemiblock (LAHB). QRS complex duration was of 0.13' with rsr' morphology in V1 and RS in V6, with negative T wave in V1 and V2. AP: +30o, AQRS: -30o, AT: 0o.

Chest radiography: Shows normal heart region and vascular markings (Figure 1).

Imaging tests: (Figure 2) Bi-Doppler Echocardiogram showed heart chambers with normal size and function. It was visualized in multiple projections, in the middle of interatrial septum, an aneurysm with convexity directed to the right, with a 20 mm distance in length between borders, without

interatrial communication. Transesophageal echocardiogram confirmed this imaging, such as the magnetic nuclear resonance. There were no myocardial abnormality and/or signs of fibrosis.

Clinical diagnosis: Interatrial septal aneurysm with full right bundle branch block, left bundle branch anterior superior block in asymptomatic patient with previous atrial fibrillation.

Clinical reasoning: Clinical elements were compatible with the diagnosis initially established of ASD reporting a mild systolic murmur on the upper left sternal border, along with CRBBB. Chest radiography, however, discarded this possibility and especially the diagnostic imaging tests. It is worth noting that, in the presence of ASD, both CRBBB and persistent or paroxysm atrial fibrillation usually occur in adulthood and in defects with great repercussion, and LAHB is rarely found in this context. Interatrial septal aneurysm is commonly found in asymptomatic patients and causes no symptoms, except the possibility of progressive thrombosis and systemic embolism in adulthood. With this analysis, heart murmur found was reported as functional and other findings, characterized as congenital and with genetic predisposition or acquired for episodes of paroxysmal atrial fibrillation, which began recently.

Differential diagnosis: Anatomical and electrical findings without clinical repercussion in this patient are not supported to characterize them as belonging to an associated syndrome or a characteristic clinical profile because in clinical practice we usually find them in isolated episodes. However, atrial aneurysm is being recently found and reported in association with CRBBB and atrial fibrillation in approximately 30% of cases. LAHB, on the other hand, is not described in this association.

Conduct: Since the findings caused no repercussion, including evolutionary problems in the short and medium term, the recommendation was for regular follow-up without limitation of usual activities. Regarding the recent atrial fibrillation, there was guidance on the use of adrenergic beta-blocker.

Comments: In children and young patients, findings in this case must be seen as precursors of evolutionary problems that may arise after a few decades of life. They are primarily represented by systemic embolisms as a result of atrial thrombosis, arrhythmias such as atrial reentry tachycardia and paroxysmal atrial fibrillation, primarily in the presence of large atrial septal aneurysms. Therefore, there is no need for concern at earlier ages. More accurate diagnostic aspects may characterize this association as mutually dependent changes. Moreover, CRBBB in childhood and teenagehood could be a relevant indicator to motivate the search for abnormalities in atrial septum as it occurs in ASD, POF or aneurysm, changes found in approximately 80% of these cases1. In this context, it is unknown the association of LAHB, found in this patient. It is considered for correcting atrial aneurysm, generally percutaneous, when the patient is symptomatic in adulthood.

e57


AtikAtrial septal aneurysm and paroxysmal fibrillation

Arq Bras Cardiol. 2014; 102(6):e57-e59

Figure 1 – Electrocardiogram in sinus rhythm enhances CRBBB and LAHB and chest radiography shows elements of normality.

e58


AtikAtrial septal aneurysm and paroxysmal fibrillation

1. Bakalli A, Koçinaj D, Georgievska-Ismail L, Bekteshi T, Pllana E, Sejdiu B. Right bundle branch block as a marker for interatrial septal abnormalities. Cardiol Young. 2012;22(1):18-25.

Reference


Figure 2 – Transesophageal echocardiogram enhances atrial septal aneurysm (arrow) in the middle of septum with convexity to the right, with normal heart chambers in A and B. In longitudinal cross-sectional view, in C, heart chambers are normal, and you can also view the atrial septal aneurysm (arrow) with normal right ventricle in RNM in D.

e59

Case Report

Short-Coupled Variant of “Torsades de Pointes” and Polymorphic Ventricular TachycardiaMuhieddine Omar Chokr, Francisco Carlos da Costa Darrieux, Carina Abigail Hardy, Denise Tessariol Hachul, Allisson Valadão de Oliveira Britto, Sissy Lara de Melo, Cristiano Pisani, Eduardo Argentino Sosa, Martino Martinelli Filho, Mauricio Ibrahim ScanavaccaInstituto do Coração da Faculdade de Medicina da Universidade de São Paulo/ InCor-FMUSP, São Paulo, SP - Brazil

Mailing Address: Mauricio Ibrahim Scanavacca •InCor-HCFMUSP, Av. Dr Enéas de Carvalho Aguiar, 44, Postal Code 05403-000 - São Paulo, SP - BrazilE-mail: [email protected] received 05/10/13, revised on 07/16/13, accepted on 09/05/13.

KeywordsTachycardia, Ventricular / therapy; Excitation Contraction

Coupling; Ventricular Premature Complexes; Arrhythmias, Cardiac.

DOI: 10.5935/abc.20140075

Introduction“Torsades de pointes” (TdP) ventricular tachycardias

carry a high risk of sudden death, even when they occur in individuals with a structurally normal heart, in the absence of myocardial ischemia or prolonged QT interval. Leenhardt et al1 described a new syndrome with these characteristics in 1994 that showed a difference in which the TdP were triggered by ventricular extrasystoles (VE) with ultra-short coupling interval (< 300 ms).

Although this condition is easily diagnosed by the described characteristics, there is a lack of data on the clinical management of patients during the phase of electrical storm and during long-term clinical outcome. Over the past 20 years, three patients were identified in our institution with this clinical condition, as well as a family member with VE and short coupling interval, asymptomatic and without documented polymorphic ventricular tachycardia (VT).

The aim of this case report is to describe the clinical management used in these patients and review the literature on the implication of the finding of VE with short coupling interval in asymptomatic family members.

Case Reports

Case 1Female patient, 20 years of age, started to have rhythmic

palpitations, initially well tolerated and self-limited in August 1993, at the same time when she had depression due to the loss of a family member. In the same month she had an episode of loss of consciousness with sphincter release that lasted approximately 10 minutes, followed by spontaneous recovery with no physical trauma. During the evolution, she started to have several episodes of short-duration palpitations. Three months later, she reported a new episode of convulsive syncope lasting approximately 8 minutes,

after which hospitalization was indicated for investigation. On the same night she was hospitalized, she had an episode of cardiac arrest in ventricular fibrillation rhythm, and underwent cardiopulmonary resuscitation. The investigation showed no evidence of structural heart disease; cardiac chamber showed preserved dimensions (LV = 47/29 mm, LVEF = 76 %; Aorta = 29 mm; LA = 27 mm, RV = 20 mm; septum and posterior wall = 8 mm each and preserved biventricular function, no segmental contractility alterations and no valvular dysfunction).

The 24-hour Holter showed VE with ultra-short coupling interval (260 ms) inducing episodes of non-sustained polymorphic ventricular tachycardia - Figure 1. The 12-lead electrocardiogram showed no alterations, the QT interval was 360 ms and QTc was 390 ms. The exercise stress test was negative for myocardial ischemia with no arrhythmia at rest or upon exertion. Coronary angiography was normal. The high-resolution electrocardiogram showed no late potentials. We performed an electrophysiological study (EPS), which showed normal basic intervals and did not induce arrhythmias when programmed ventricular stimulation was performed in the apex and right ventricular outflow tract, as well as using 'short-long-short' cycles for induction of VT/VF during sensitization with isoproterenol. The patient started to receive verapamil 80 mg every 8 hours and received an implantable cardioverter-defibrillator (ICD).

The patient needed psychological counseling after these events. During follow-up, she still had episodes of non-sustained polymorphic ventricular tachycardia, seen at the 24-hour Holter, requiring a dose of 480 mg/day of verapamil to control the arrhythmia. She then remained asymptomatic for several years, although the 24-hour Holter still showed VE with short-coupling interval (260 ms). Seventeen years after the diagnosis and two ICD generator replacements, the patient received adequate defibrillator therapy; during an evaluation, she reported poor compliance to treatment with calcium channel blockers. At follow-up, she showed no significant emotional alterations, ischemic changes or ventricular function worsening.

Case 2Female patient, 52 years old, admitted at another service

due to episodes of recurrent syncope in 2010. At the time, she had suffered the recent loss of a son in a car accident and was drinking a type of "tea for weight loss." The electrocardiographic monitoring showed episodes of rapid ventricular tachycardia (Figures 2A and 2B). Within hours, the patient developed electrical storm and needed defibrillation for more than 50 times

e60

Case Report

Chokr et al.Short-Coupled “Torsades de Pointes” and Ventricular Tachycardia


Figure 1 – 24-hour Holter: A. Extrasystole with ultrashort coupling interval (260 ms). B. Episode of non-sustained polymorphic ventricular tachycardia initiated by extrasystoles with short-coupling interval.

during a 24-hour period, requiring sedation and orotracheal intubation. An attempt was made to suppress the arrhythmias with isoproterenol, which was not successful.

Recurrence was observed in less than 6 hours after the start of drug infusion. A temporary pacemaker was implanted in the right ventricle, performed on stimulation without

arrhythmia suppression. She was clinically stable after 48 hours of deep sedation and administration of verapamil at a dose of 240 mg/day.

The investigation showed no structural heart disease at the echocardiography, MRI and coronary angiography. The 24-h Holter monitoring, performed after crisis stabilization,

Figure 2A – Electrical Storm - Moment of electrical cardioversion with 200 J and Torsades de Pointes reversal to sinus rhythm.

e61

Case Report



Figure 2B – 12-lead ECG with extrasystole and short coupling interval (280 ms).

showed 960 VE/24 h, with several of them showing short coupling (+/- 280 ms) and the same morphology. There were no tachycardias. At the ECG, the QTc was 400 ms. Electrophysiological mapping and attempted VE ablation were not successful. The scarcity of extrasystoles during the procedure did not induce arrhythmias when programmed ventricular stimulation was performed in the apex and right ventricular outflow tract, as well as using 'short-long-short' cycles for of VT/ VF induction under sensitization with isoproterenol. ICD implantation was indicated and treatment with verapamil was maintained. The patient remains asymptomatic during the two-year follow-up.

Case 3This is an asymptomatic, 18-year-old woman, the

daughter of the patient described in case # 2. During family screening, she was diagnosed with VE with a coupling of approximately 300 ms (17 extrasystoles in 24 h) during a 24-h Holter monitoring. Because the patient was asymptomatic and due to the low-density VE, it was decided to prescribe verapamil 160 mg/day and keep her on frequent clinical monitoring. She remains asymptomatic after a follow-up period of 48 months.

Case 4Female patient, 39 years old, with episodes of syncope

preceded by sudden and fast malaise, without trauma and unrelated to exertion, some occurring at night, during sleep, at an approximate frequency of three times a week since March 2011. She sought medical attention a few times, having been diagnosed with anxiety and prescribed anxiolytics, with no improvement of symptoms and worsening

of anxiety. On 07/10/2011, she had recurrence of syncope, with characteristics similar to those described, when she was admitted at another hospital for diagnosis.

The patient had no family history of cardiac arrhythmias or sudden death. Physical examination was normal. The initial ECG showed no abnormalities. The exercise s t ress test was negat ive for i schemia and di not trigger arrhythmias. The echocardiogram showed a structurally normal heart (LV = 52/35 mm, LVEF = 60%; Aorta = 33 mm; LA = 35 mm; septum and posterior wall = 9 mm; preserved biventricular function, no segmental alterations in contractility and mitral valve prolapse with discrete meso-systolic leak). Cardiac magnetic resonance imaging also ruled out structural heart disease showing preserved cardiac chamber dimensions with normal biventricular function (LVEF = 70% and RVEF = 69%), without the presence of myocardial fibrosis.

The Holter monitoring showed several polymorphic VE with short-coupling interval, some of them inducing nonsustained polymorphic ventricular tachycardia initiated by extrasystoles with R-on-T phenomenon, with coupling between 350 and 370 ms, and QT intervals within normal limits.

The coronary angiography ruled out the presence of obstructive coronary artery disease. She was prescribed diltiazem 180 mg/day and a defibrillator implant was indicated, performed in August 2011. As the VE persisted (density 2%) with episodes of non-sustained polymorphic ventricular tachycardia, diltiazem was substituted by verapamil 240 mg/day in September 2011. New 24-h Holter monitoring showed a significant reduction in the density of arrhythmias (<1%), increase in minimum coupling interval of extrasystoles to 370 ms and absence

e62

Case Report



of episodes of non-sustained polymorphic ventricular tachycardia, always with a normal QT interval. The patient became asymptomatic, with no further episodes of syncope or ICD therapies, during a nine-month follow up.

DiscussionDescribed by Dessertenne2 in 1966, TdP ventricular

has a typical ECG pattern, with progressive changes in morphology, amplitude and polarity of the QRS complex of which peaks cross the baseline before spontaneously terminating. This phenomenon is preceded by a long-short cycle that triggers the tachycardia, usually after a long coupling interval (600 to 800 ms). The scenario of this arrhythmia includes long QT syndrome in its congenital and acquired forms, as well as the precipitating factors, such as electrolyte disturbances.

Three decades later, in 1994, Leenhardt et al1 published a series of 14 patients without structural heart disease and a history of syncope, whose electrocardiographic monitoring showed TdP polymorphic ventricular tachycardia with normal QT intervals, initiated by VE with short coupling interval (200 - 300 ms). One third of these patients had a family history of sudden death, and approximately 70% had TdP degenerating into ventricular fibrillation during a mean follow-up of seven years. The morphology of isolated VE and those that initiated the TdP was similar in nine patients, with most triggering VE showing left bundle branch block morphology and axis deviated to the left.

In general, the EPS did not reproduce the clinical arrhythmia. The only drug that partially suppressed arrhythmia was verapamil, increasing the VE coupling interval and reducing its density. However, it was not able to prevent sudden death, which is why the ICD is indicated for all patients with this disease.

In the following year, a series of 15 patients with the same characteristics (absence of structural heart disease, normal QT interval) that had episodes of TdP polymorphic ventricular tachycardia initiated by VE with short coupling interval was published. It was demonstrated that the smaller the coupling interval of these extrasystoles, the greater the risk of spontaneous polymorphic ventricular tachycardia, and, therefore, of sudden death due to ventricular fibrillation. No medication was able to prevent this outcome3.

In the two largest case series published, similar to our three patients, we observed that the initial clinical presentation was syncope preceded or not by palpitations and the occurrence was predominantly in females. The age of symptom onset ranged from the second to the fifth decade of life and two of our patients were going through major psychological problems, which is described as a potential trigger for the clinical manifestation of the disease2. The mean coupling interval measured from the beginning of the QRS preceding the extrasystole, at the beginning of the latter, was + / - 280 ms. Verapamil has been prescribed to all patients, although the literature reports the frequent occurrence of appropriate ICD therapy and sudden death, in which the defibrillator had not been implanted, despite medication use3.

A case of electrical storm and recovered cardiac arrest triggered by VE with ultrashort coupling interval in a 50-year-old patient was recently published. Similar to our patient in case number 2, there were several episodes of spontaneous TdP polymorphic ventricular tachycardia, some of them developing into ventricular fibrillation requiring cardiorespiratory resuscitation and electrical defibrillation.

Several intravenous medications have been tried, including lidocaine, amiodarone and magnesium, without control of arrhythmia. Ventricular pacing with temporary pacemaker electrode resulted in arrhythmia exacerbation. However, unlike our patient, the infusion of isoproterenol until a heart rate of 100 bpm is achieved showed to be capable of suppressing ventricular arrhythmias. Electrode implantation in the right atrium and its stimulation at a frequency of 85 bpm was effective in arrhythmia remission. After ICD implantation with atrial pacing of 85 bpm, the patient had no symptoms and no evidence of arrhythmias during a three-month follow-up4.

There is no consensus in the literature regarding what the normal value of the VE coupling interval is. In the patient from case number 4, the shortest coupling interval recorded was 360 ms, with several episodes of NSVT occurring with VE of up to 370 ms, with morphological characteristics similar to those from the other three cases. A clinical hypothesis is that it is the same genetic mutation with varying degrees of gene penetration and consequently, different clinical expressions. Therefore, individuals with the more severe form of disease could potentially trigger malignant arrhythmias without necessarily having a coupling interval < 300 ms.

In 2002, Haissaguerre et al5 described the VE with short coupling interval originating from the distal Purkinje fibers as the main triggering factors of idiopathic VF. These extrasystoles had different morphologies and were mapped in several locations of the Purkinje system, including the anterior right ventricular region and large areas of the lower half of the left ventricular septum. The authors ruled out these triggers by focal catheter ablation in 27 patients.

Throughout a mean follow up of 24 months, 89% of patients had no recurrence of ventricular fibrillation5. These findings demonstrate that a therapeutic possibility in this patient population would be treatment by catheter ablation; however, it should be noted that all patients were under the protection of an ICD. In our series, two patients underwent attempted ablation of VE, but the non-occurrence of VE during the procedure prevented their accurate mapping, which would justify the moment of the electrical storm as the ideal setting for the attempted ablation. Another indication for ablative therapy would be cases of appropriate therapies for the ICD, refractory to use of calcium channel blockers.

Regarding family screening, there is no specific reference in the literature about the best management and medical decision in asymptomatic individuals remains controversial. All four patients in our series underwent family screening and extrasystoles with short coupling interval were found in the daughter of Patient 2. Due to the limited data in the literature in asymptomatic individuals, together with the family, we chose to institute a clinical follow-up and prophylactic and empiric prescription of verapamil.

e63

Case Report



1. Leenhardt A, Glaser E, Burguera M, Nürnberg M, Maison-Blanche P, Coumel P. Short-coupled variant of torsade de pointes: a new electrocardiographic entity in the spectrum of idiopathic ventricular tachyarrhythmias. Circulation. 1994;89(1):206-15.

2. Dessertenne F. La tachycardie ventriculaire á deux foyers opposes variables. Arch Mal Coeur Vaiss. 1966;59(2):263-72.

3. Eisenberg SJ, Scheinman MM, Dullet NK, Finkbeiner WE, Griffin JC, Eldar M, et al. Sudden cardiac death and polymorphous ventricular tachycardia in patients with normal QT intervals and normal systolic cardiac function. Am J Cardiol. 1995;75(10):687-92.

4. Chiladakis JA, Spiroulias G, Koutsogiannis N, Zagli F, Alexopoulos D. Short-coupled variant of Torsade de Pointes as a cause of electrical storm and aborted sudden cardiac death: insights into mechanism and treatment. Hellenic J Cardiol. 2008;49(5):360-4.

5. Haïssaguerre M, Shoda M, Jais P, Nogami A, Shah DC, Kautzner J, et al. Mapping and ablation of idiopathic ventricular fibrillation Circulation. 2002;106(8):962-7.

References

ConclusionsVE patients with short coupling may carry a rare syndrome,

probably of genetic etiology, which can result in TdP. Verapamil is apparently the most effective drug for alleviating the occurrence of these arrhythmias; however, it is not effective enough to eliminate the need for an ICD. Ablation of VE could reduce the incidence of TdP; however, there are still technical limitations to its effective implementation. A new look at the disease and the knowledge of this rare heart rhythm disorder is needed so that cardiologists can be able to recognize this electrocardiographic detail and thus identify apparently healthy individuals at risk of genetically determined sudden death.

Author contributionsConception and design of the research: Chokr MO,

Britto AVO, Scanavacca MI; Acquisition of data: Chokr MO, Darrieux FCC, Hardy CA, Hachul DT, Britto AVO, Melo

SL, Pisani C, Sosa EA, Martinelli Filho M, Scanavacca MI; Statistical analysis: Chokr MO, Scanavacca MI; Analysis and interpretation of the data: Chokr MO, Sosa EA, Scanavacca MI; Writing of the manuscript: Chokr MO, Britto AVO, Scanavacca MI; Critical revision of the manuscript for intellectual content: Chokr MO, Darrieux FCC, Scanavacca MI.



Sources of Funding


Study Association

This study is not associated with any thesis or dissertation work.

e64

Viewpoint

Cardiohepatic Interactions – from Humoral Theory to Organ TransplantationOdilson Marcos Silvestre1, Fernando Bacal1, Rafael Oliveira Ximenes2, Flair José Carrilho2, Luiz Augusto Carneiro D’Albuquerque2, Alberto Queiroz Farias2

Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo1; Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo2, São Paulo, SP - Brazil

IntroductionHeart and liver were already put into reciprocal interaction

when attempting to explain the health-disease process from the humoral theory. This suggestion attributed to Empedocles (490 BC), and later applied to medicine by Hippocrates (460 BC) and Galen (AD 129), despite being devoid of any pathophysiological basis, suggested that such organs were protagonists of illness by participating in the production of blood and yellow bile, two of the four humors whose imbalance would be closely related to the emergence of diseases. With the progress of knowledge of physiology and pathophysiology, the close relationship between heart and liver has been defined more precisely.

In this article, we will discuss the cardiohepatic interactions subdividing them didactically in the following: (1) impact of heart diseases on the liver; (2) effects of liver failure and portal hypertension on the heart; and (3) concomitant diseases affecting both the liver and the heart.

Impact of heart disease on the liver (cardiac hepatopathy)The liver is an organ sensitive to hemodynamic changes.

Due to its high metabolic activity, it receives around 25% of the cardiac output, coming by two systems of blood vessels: the hepatic artery and the portal vein. The venous drainage occurs by hepatic veins and the inferior vena cava, which have no valves, resulting in direct transmission of the rise of right heart filling pressures to the liver. The systemic circulatory disorders transmitted to the liver determine two major forms of liver damage: the ischemic hepatitis and the congestive liver disease or congestive liver (formerly named cardiac cirrhosis).

The former, called “shock liver”, today known as ischemic hepatitis, occurs in some cases of cardiogenic shock. There is a predominant change of the aminotransferases (ALT and AST), with elevation up to 10 to 20 times the upper limit of the normal value1. Such hepatitis should be differentiated from those caused by drugs (many of them used in cardiology),

Mailing Address: Odilson Marcos Silvestre •Avenida Dr. Eneas de Carvalho Aguiar, 255, sala 9117.Postal Code: 05403-000, São Paulo, SP - BrazilE-mail: [email protected]; [email protected] received 28/01/2014; revised 14/02/2014; accepted 18/02/2014.

KeywordsHeart failure; Hypertension, portal; Hepatic insufficiency;

Liver diseases; Liver cirrhosis / complications.

DOI: 10.5935/abc.20140079

acute viral hepatitis and from chronic hepatitis exacerbation of different etiologies. To aid in the differential diagnosis, the pattern of the curve of aminotransferases should be taken into account, with aminotransferases increasing a few hours after the injury and improving with the resolution of the circulatory dysfunction. Serum levels start to reduce within 48 to 72 hours after the event, with normalization in 10 to 14 days. Another feature that assists in identifying the ischemic hepatitis is the marked increase in lactic dehydrogenase, which doesn’t usually happen in hepatitis by other causes.

Congestive liver disease is more frequent than ischemic hepatitis. Studies on liver biopsy in candidates for implantable ventricular assistance devices show findings compatible with cirrhosis in 34% of patients2. Congestive liver disease can manifest itself with pain in the right hypochondrium, sensation of abdominal growth and early satiety. In laboratorial tests, changes suggestive of cholestasis are displayed, i.e. increased canaliculares enzymes, with varying degrees of elevated bilirubins. Around 19% of outpatients show elevation of these markers. The finding of increasing canaliculares enzymes in blood demonstrates greater severity of heart failure (HF)3.

Recently, with the incorporation of new technologies for the treatment of refractory HF, the assessment of hepatic effects has gained importance. Liver markers denote the prognosis in candidates for implantable ventricular assistance devices. The MELD score (Model for End-Stage Liver Disease), numeric scale of severity in the short term for liver disease and extensively used in the management of liver transplantation lists, has emerged as a promising marker to identify the best candidates for treatment with such devices.

Effects of liver failure and portal hypertension in the heartCirculatory changes associated with cirrhosis have been

described for more than 60 years, when it was observed that patients with alcoholic cirrhosis showed increased cardiac output, decreased systemic vascular resistance and reduction of arteriovenous oxygen gradient. The decrease of systemic vascular resistance leads to a state of central hypovolemia, which, in turn, activates the sympathetic nervous system and the renin-angiotensin-aldosterone system. The activation of these neuro-humoral axes and the consequent hyperdynamic circulation in cirrhosis can lead to morphological and functional changes, especially cardiac dilatation of the left chambers4. The so called cirrhotic cardiomyopathy is characterized by the presence of the following parameters: cirrhosis, systolic dysfunction under stress conditions (decreased systolic reserve) with normal systolic function at rest, diastolic dysfunction and change of

e65

Viewpoint

Silvestre et al.Cardiohepatic interactions


repolarization evidenced by QT interval prolongation, in the absence of any primary heart disease5.

Some authors suggest that cirrhotic cardiomyopathy would be implicated in the emergence of complications of cirrhosis as ascites and hepatorenal syndrome. In cases of spontaneous bacterial peritonitis patients with lower cardiac output have worse prognosis6. In liver transplantation, the manifestation of cirrhotic cardiomyopathy can be associated to post-reperfusion syndrome. This is characterized by increased cardiac filling pressures with decrease in cardiac index after reperfusion of liver graft. An incidence of more than 20% of post-reperfusion syndrome is reported, but the prognostic implication of such a complication is not clearly defined. The real impact of cirrhotic cardiomyopathy in clinical evolution of cirrhosis is unknown, because there is no clear definition of either the entity or its diagnostic criteria and even fewer prospective studies with evaluation of their effect.

Portal hypertension, usually associated with cirrhosis, may cause pulmonary circulatory complications and therefore repercussions both on the right and on the left cardiac chambers. The portopulmonary hypertension is a form of precapillary pulmonary arterial hypertension whose prevalence is of 5% among patients with cirrhosis. It is a known factor of worse prognosis. In perioperative of liver transplantation, severe portopulmonary hypertension is associated with right ventricular failure and mortality rates of up to 100%, being one of the factors of contraindication to surgery. The hepatopulmonary syndrome is an important cause of hypoxemia among patients with cirrhosis, with a prevalence of 20% on the liver transplantation waiting list. It is characterized by: portal hypertension, hypoxemia and intrapulmonary fistulas. Recent data show that in patients with cirrhosis, the volume of the left atrium above 50 ml is associated with the presence of hepatopulmonary syndrome.

Diseases concomitantly affecting liver and heartThe modern lifestyle is associated with high prevalence

of metabolic syndrome, a condition associated with the development of non-alcoholic steatohepatitis (NASH) and coronary heart disease. The presence of NASH is an independent risk factor for atherosclerotic disease, being that, among patients with cirrhosis by NASH, there is prevalence of 23% of severe coronary atherosclerotic disease. This data is relevant in cardiac evaluation prior to liver transplantation, where in the cases of cirrhosis by NASH, one must consider the increased risk of concomitant coronary heart disease and increased risk of perioperative cardiovascular events.

Other systemic diseases may compromise liver and heart by targeting both organs parenchyma. In a series of 32 patients with concomitant liver and heart dysfunction, hepatic and cardiac biopsy showed that nine (28%) patients presented the same etiology, the diagnosed diseases being: haemochromatosis, alcoholism and amyloidosis7.

The definition of disease concomitance and severity of failure in each organ is an important step of treatment strategy. Advanced failures of both organs have been addressed by performing double transplantation (heart and liver) in some medical centers. However, often it is not

possible to define which component is largely responsible for clinical manifestations. Depending on the clinical profile, it is possible to use biological markers in the definition of the involvement and the magnitude of the disease in one organ or the other. In cases where there is ascites in patients with cardiac and hepatic dysfunction, propaedeutics must be the instrument of differentiation, but the serum dosage of B-type natriuretic peptide can help to define the cause of ascites and, consequently, help to guide treatment.

ConclusionThe knowledge of the interactions between liver and heart

guides the management of different organ dysfunctions, which on first impression, appear unrelated from the etiopathogenic point of view. Evaluation of liver function is particularly important for the treatment of refractory HF, for organ transplantation and device implantation recommendations. The detailed cardiac assessment, in turn, must not be forgotten in cases of metabolic syndrome, non-alcoholic steatohepatitis, not to mention its critical importance for liver transplantation, notably due to the effects of cirrhotic cardiomyopathy in surgical risk and prognosis. Still, one must take into account that same disease can cause both hepatic and cardiac dysfunction.

Knowing that the liver and the heart are attuned, Pablo Neruda, Nobel Prize for literature in 1971, was not mistaken in his “Ode to the liver” by asking these two noble organs to keep working in harmony:

“...While the heart resounds and attracts the music of the mandolin, there, inside, you filter and apportion, you separate and divide, you multiply and lubricate, you raise and gather the threads and the grams of life, the final distillate, ... giver of syrups and of poisons, regulator of salts, from you I hope for justice: I love life: Do not betray me! Work on!”

Author contributionsConception and design of the research: Silvestre OM, Bacal

F, Carrilho FJ, D’Albuquerque LAC, Farias AQ; Writing of the manuscript: Silvestre OM, Ximenes RO, Farias AQ; Critical revision of the manuscript for intellectual content: Silvestre OM, Bacal F, Ximenes RO, Carrilho FJ, D’Albuquerque LAC, Farias AQ.


was reported.


Study AssociationThis article is part of the Doctoral Thesis submitted by

Odilson Marcos Silvestre, from Universidade de São Paulo.

e66

Viewpoint

Silvestre et al.Cardiohepatic interactions


1. Seeto RK, Fenn B, Rockey DC. Ischemic hepatitis: clinical presentation and pathogenesis. Am J Med. 2000;109(2):109-13.

2. Gelow JM, Desai AS, Hochberg CP, Glickman JN, Givertz MM, Fang JC. Clinical predictors of hepatic fibrosis in chronic advanced heart failure. Circ Heart Fail. 2010;3(1):59-64.

3. Poelzl G, Ess M, Mussner-Seeber C, Pachinger O, Frick M, Ulmer H. Liver dysfunction in chronic heart failure: prevalence, characteristics and prognostic significance. Eur J Clin Invest. 2012;42(2):153-63.

4. Silvestre OM, Bacal F, de Souza Ramos D, Andrade JL, Furtado M, Pugliese V, et al. Impact of the severity of end-stage liver disease in cardiac structure and function. Ann Hepatol. 2013;12(1):85-91.

5. Zardi EM, Abbate A, Zardi DM, Dobrina A, Margiotta D, Van Tassel BW. Cirrhotic cardiomyopathy. J Am Coll Cardiol. 2010;56(7):539-49. Erratum in J Am Coll Cardiol. 2010;56(12):1000.

6. Ruiz-del-Arbol L, Monescillo A, Arocena C, Valer P, Ginès P, Moreira V, et al. Circulatory function and hepatorenal syndrome in cirrhosis. Hepatology 2005;42(2):439-47.

7. Ocel JJ, Edwards WD, Tazelaar HD, Petrovic LM, Edwards BS, Kamath OS. Heart and Liver Disease in 32 Patients Undergoing Biopsy of Both Organs, With Implications for Heart or Liver Transplantation. Mayo Clin Proc. 2004;79(4):492-501.

8. Farias AQ, Silvestre OM, Garcia-Tsao G, da Costa Seguro LF, de Campos Mazo DF, Bacal F, et al. Serum b-type natriuretic peptide in the initial workup of patients with new onset ascites: A diagnostic accuracy study. Hepatology. 2014;59(3):1043-51.

References

e67

· auis bsileis de cdili - volume 102, 6, une 2014 a journal of sociedade brasileira de...

Documents