Guideline of the Brazilian Society of Cardiology on Diagnosis and Treatment of Patients with Chagas Disease Cardiomyopathy / Diretriz da Sociedade Brasileira de Cardiologia sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas

This guideline aimed to update the concepts and formulate the standards of conduct and scientific evidence that support them, regarding the diagnosis and treatment of the Cardiomyopathy of Chagas disease, with special emphasis on the rationality base that supported it.  Chagas disease in the 21st century maintains an epidemiological pattern of endemicity in 21 Latin American countries. Researchers and managers from endemic and non-endemic countries point to the need to adopt comprehensive public health policies to effectively control the interhuman transmission of T. cruzi infection, and to obtain an optimized level of care for already infected individuals, focusing on diagnostic and therapeutic opportunistic opportunities.   Pathogenic and pathophysiological mechanisms of the Cardiomyopathy of Chagas disease were revisited after in-depth updating and the notion that necrosis and fibrosis are stimulated by tissue parasitic persistence and adverse immune reaction, as fundamental mechanisms, assisted by autonomic and microvascular disorders, was well established. Some of them have recently formed potential targets of therapies.  The natural history of the acute and chronic phases was reviewed, with enhancement for oral transmission, indeterminate form and chronic syndromes. Recent meta-analyses of observational studies have estimated the risk of evolution from acute and indeterminate forms and mortality after chronic cardiomyopathy. Therapeutic approaches applicable to individuals with Indeterminate form of Chagas disease were specifically addressed. All methods to detect structural and/or functional alterations with various cardiac imaging techniques were also reviewed, with recommendations for use in various clinical scenarios. Mortality risk stratification based on the Rassi score, with recent studies of its application, was complemented by methods that detect myocardial fibrosis.  The current methodology for etiological diagnosis and the consequent implications of trypanonomic treatment deserved a comprehensive and in-depth approach. Also the treatment of patients at risk or with heart failure, arrhythmias and thromboembolic events, based on pharmacological and complementary resources, received special attention. Additional chapters supported the conducts applicable to several special contexts, including t. cruzi/HIV co-infection, risk during surgeries, in pregnant women, in the reactivation of infection after heart transplantation, and others.     Finally, two chapters of great social significance, addressing the structuring of specialized services to care for individuals with the Cardiomyopathy of Chagas disease, and reviewing the concepts of severe heart disease and its medical-labor implications completed this guideline.

Esta diretriz teve como objetivo principal atualizar os conceitos e formular as normas de conduta e evidências científicas que as suportam, quanto ao diagnóstico e tratamento da CDC, com especial ênfase na base de racionalidade que a embasou. A DC no século XXI mantém padrão epidemiológico de endemicidade em 21 países da América Latina. Investigadores e gestores de países endêmicos e não endêmicos indigitam a necessidade de se adotarem políticas abrangentes, de saúde pública, para controle eficaz da transmissão inter-humanos da infecção pelo T. cruzi, e obter-se nível otimizado de atendimento aos indivíduos já infectados, com foco em oportunização diagnóstica e terapêutica. Mecanismos patogênicos e fisiopatológicos da CDC foram revisitados após atualização aprofundada e ficou bem consolidada a noção de que necrose e fibrose sejam estimuladas pela persistência parasitária tissular e reação imune adversa, como mecanismos fundamentais, coadjuvados por distúrbios autonômicos e microvasculares. Alguns deles recentemente constituíram alvos potenciais de terapêuticas. A história natural das fases aguda e crônica foi revista, com realce para a transmissão oral, a forma indeterminada e as síndromes crônicas. Metanálises recentes de estudos observacionais estimaram o risco de evolução a partir das formas aguda e indeterminada e de mortalidade após instalação da cardiomiopatia crônica. Condutas terapêuticas aplicáveis aos indivíduos com a FIDC foram abordadas especificamente. Todos os métodos para detectar alterações estruturais e/ou funcionais com variadas técnicas de imageamento cardíaco também foram revisados, com recomendações de uso nos vários cenários clínicos. Estratificação de risco de mortalidade fundamentada no escore de Rassi, com estudos recentes de sua aplicação, foi complementada por métodos que detectam fibrose miocárdica. A metodologia atual para diagnóstico etiológico e as consequentes implicações do tratamento tripanossomicida mereceram enfoque abrangente e aprofundado. Também o tratamento de pacientes em risco ou com insuficiência cardíaca, arritmias e eventos tromboembólicos, baseado em recursos farmacológicos e complementares, recebeu especial atenção. Capítulos suplementares subsidiaram as condutas aplicáveis a diversos contextos especiais, entre eles o da co-infecção por T. cruzi/HIV, risco durante cirurgias, em grávidas, na reativação da infecção após transplante cardíacos, e outros.    Por fim, dois capítulos de grande significado social, abordando a estruturação de serviços especializados para atendimento aos indivíduos com a CDC, e revisando os conceitos de cardiopatia grave e suas implicações médico-trabalhistas completaram esta diretriz. 

Predictors of mortality and heart transplantation in patients with Chagas' cardiomyopathy and ventricular tachycardia treated with implantable cardioverter-defibrillators.

AIMS: Data on long-term follow-up of patients with Chagas' heart disease (ChHD) receiving a secondary prevention implantable cardioverter-defibrillator (ICD) are limited and its benefit is controversial. The aim of this study was to evaluate the long-term outcomes of ChHD patients who received a secondary prevention ICD. METHODS AND RESULTS: We assessed the outcomes of consecutive ChHD patients referred to our Institution from 2006 to 2014 for a secondary prevention ICD [89 patients; 58 men; mean age 56 ± 11 years; left ventricular ejection fraction (LVEF), 42 ± 12%]. The primary outcome included a composite of death from any cause or heart transplantation. After a mean follow-up of 59 ± 27 months, the primary outcome occurred in 23 patients (5.3% per year). Multivariate analysis showed that LVEF < 35% [hazard ratio (HR) 4.64; P < 0.01] and age ≥ 65 years (HR 3.19; P < 0.01) were independent predictors of the primary outcome. Using these two risk factors, a risk score was developed, and lower- (no risk factors), intermediate- (one risk factor), and higher-risk (two risk factors) groups were recognized with an annual rate of primary outcome of 1.4%, 7.4%, and 20.4%, respectively. A high burden of appropriate ICD therapies (16% per year) and electrical storms were documented, however, ICD interventions did not impact on the primary outcome. CONCLUSION: Among ChHD patients receiving a secondary prevention ICD, older age (≥65 years) and left ventricular dysfunction (LVEF < 35%) portend a poor outcome and were associated with increased risk of death or heart transplantation. Most patients received appropriate ICD therapies, however, ICD interventions did not impact on the primary outcome.

Is It Conceivable to Still Perform the Cut and Sew Cox Maze III Procedure in the Current Era?

To determine whether cut and sew Cox maze III procedure is still associated with adequate safety endpoints when performed in conjunction with other open-heart procedures. Between January 2008 and January 2015, 113 consecutive adult patients were submitted to cut and sew Cox maze III procedure in association with other operations for structural heart disease. Mean age was 49 years and 80 (70.8%) were females. Longstanding or persistent atrial fibrillation has occurred in 87.6% and rheumatic heart disease in 80.7%. Valve surgery was performed in 98.2%. The number of associated procedures was correlated with morbidity and hospital mortality. Overall mean cardiopulmonary bypass and aortic cross-clamping times were 129 ±â€¯26 and 105 ±â€¯23 minutes, respectively. Hospital mortality was 1.77%, re-exploration for bleeding 0.9%, cerebrovascular accident 1.8%, and acute renal failure requiring hemodialysis 2.6%. The greater number of associated procedures did not correlate with poorer safety outcomes. Permanent pacemaker was required in 18.2% of those with three associated procedures, as opposed to 4% with two procedures and no requirement with one procedure (P = .01). Frequency of sinus rhythm was 88%, 88%, and 85% at 6, 12, and 24 months, respectively. In a contemporary single-center cohort of predominantly rheumatic patients, the surgical treatment of atrial fibrillation associated with structural heart disease by means of cut and sew Cox maze III procedure is safe, with low morbidity and mortality rates. Surgical complexity, defined by number of associated procedures, did not translate into poorer safety endpoints, except for greater need of permanent pacemaker.

Transvenous dual-chamber pacemaker after paediatric heart transplantation using left ventricle pacing through the coronary sinus.

A 12-year-old child with end-stage heart failure due to restrictive cardiomyopathy was submitted to orthotopic heart transplantation. Primary graft dysfunction required venous arterial extra-corporeal membrane oxygenation. Heart function normalized, but complete atrioventricular block remained after 3 weeks. A dual-chamber pacing with transvenous left ventricle pacing through the coronary sinus was performed. At 5-year follow-up, the patient is stable with the same pacing system and with preserved ventricular function.

Late Results of Cox Maze III Procedure in Patients with Atrial Fibrillation Associated with Structural Heart Disease.

Background: Cox-Maze III procedure is one of the surgical techniques used in the surgical treatment of atrial fibrillation (AF). Objectives: To determine late results of Cox-Maze III in terms of maintenance of sinus rhythm, and mortality and stroke rates. Methods: Between January 2006 and January 2013, 93 patients were submitted to the cut-and-sew Cox-Maze III procedure in combination with structural heart disease repair. Heart rhythm was determined by 24-hour Holter monitoring. Procedural success rates were determined by longitudinal methods and recurrence predictors by multivariate Cox regression models. Results: Thirteen patients that obtained hospital discharge alive were excluded due to lost follow-up. The remaining 80 patients were aged 49.9 ± 12 years and 47 (58.7%) of them were female. Involvement of mitral valve and rheumatic heart disease were found in 67 (83.7%) and 63 (78.7%) patients, respectively. Seventy patients (87.5%) had persistent or long-standing persistent AF. Mean follow-up with Holter monitoring was 27.5 months. There were no hospital deaths. Sinus rhythm maintenance rates were 88%, 85.1% and 80.6% at 6 months, 24 months and 36 months, respectively. Predictors of late recurrence of AF were female gender (HR 3.52; 95% CI 1.21-10.25; p = 0.02), coronary artery disease (HR 4.73 95% CI 1.37-16.36; p = 0.01) and greater left atrium diameter (HR 1.05; 95% CI 1.01-1.09; p = 0.02). Actuarial survival was 98.5% at 12, 24 and 48 months and actuarial freedom from stroke was 100%, 100% and 97.5% in the same time frames. Conclusions: The Cox-Maze III procedure, in our experience, is efficacious for sinus rhythm maintenance, with very low late mortality and stroke rates.

Fundamento: A operação de Cox-Maze III é uma das variantes técnicas no tratamento cirúrgico da fibrilação atrial (FA). Objetivos: Estudar os resultados tardios da operação de Cox-Maze III, quanto à eficácia na manutenção de ritmo sinusal e taxas de mortalidade e acidente vascular cerebral (AVC). Métodos: Entre janeiro de 2006 a janeiro de 2013, 93 pacientes foram submetidos a operação de Cox-Maze III por corte e sutura associada a correção de cardiopatias estruturais. Avaliação do ritmo cardíaco ocorreu por Holter 24 horas. Taxas de sucesso da operação foram estudadas por métodos longitudinais e os preditores de recorrência por análise de regressão de Cox multivariada. Resultados: Foram excluídos 13 pacientes sobreviventes ao período intra-hospitalar cujo seguimento tardio não foi possível. Os 80 pacientes restantes tinham idade média de 49,9 ± 12 anos e 47 (58,75%) eram do sexo feminino. Acometimento da valva mitral ocorreu em 67 pacientes (83,7%). Valvopatia reumática ocorreu em 63 (78,7%). Setenta pacientes (87,5%) tinham fibrilação atrial persistente ou persistente de longa duração. O tempo médio de seguimento clínico com avaliação de Holter foi de 27,5 meses. Não houve óbitos intra-hospitalares. As taxas de manutenção de ritmo sinusal foram 88%, 85,1% e 80,6% aos 6 meses, 24 meses e 36 meses, respectivamente. Os preditores de recorrência tardia foram sexo feminino (RR 3,52; IC 95% 1,21-10,25; p = 0,02), doença arterial coronária (RR 4,73; IC 95% 1,37-16,36; p = 0,01) e maior diâmetro de átrio esquerdo (RR 1,05; IC 95% 1,01-1,09; p = 0,02). A sobrevida atuarial aos 12, 24 e 48 meses foi de 98,5% e as taxas atuariais livres de AVC nos mesmos períodos de 100%, 100% e 97,5%. Conclusões: A operação de Cox-Maze III, na nossa experiência, é eficaz na manutenção do ritmo sinusal, com baixíssimos índices de mortalidade e de AVC tardios.

Late Results of Cox Maze III Procedure in Patients with Atrial Fibrillation Associated with Structural Heart Disease / Resultados Tardios da Operação de Cox Maze III em Pacientes com Fibrilação Atrial Associada A Doença Cardíaca Estrutural

Abstract Background: Cox-Maze III procedure is one of the surgical techniques used in the surgical treatment of atrial fibrillation (AF). Objectives: To determine late results of Cox-Maze III in terms of maintenance of sinus rhythm, and mortality and stroke rates. Methods: Between January 2006 and January 2013, 93 patients were submitted to the cut-and-sew Cox-Maze III procedure in combination with structural heart disease repair. Heart rhythm was determined by 24-hour Holter monitoring. Procedural success rates were determined by longitudinal methods and recurrence predictors by multivariate Cox regression models. Results: Thirteen patients that obtained hospital discharge alive were excluded due to lost follow-up. The remaining 80 patients were aged 49.9 ± 12 years and 47 (58.7%) of them were female. Involvement of mitral valve and rheumatic heart disease were found in 67 (83.7%) and 63 (78.7%) patients, respectively. Seventy patients (87.5%) had persistent or long-standing persistent AF. Mean follow-up with Holter monitoring was 27.5 months. There were no hospital deaths. Sinus rhythm maintenance rates were 88%, 85.1% and 80.6% at 6 months, 24 months and 36 months, respectively. Predictors of late recurrence of AF were female gender (HR 3.52; 95% CI 1.21-10.25; p = 0.02), coronary artery disease (HR 4.73 95% CI 1.37-16.36; p = 0.01) and greater left atrium diameter (HR 1.05; 95% CI 1.01-1.09; p = 0.02). Actuarial survival was 98.5% at 12, 24 and 48 months and actuarial freedom from stroke was 100%, 100% and 97.5% in the same time frames. Conclusions: The Cox-Maze III procedure, in our experience, is efficacious for sinus rhythm maintenance, with very low late mortality and stroke rates.

Resumo Fundamento: A operação de Cox-Maze III é uma das variantes técnicas no tratamento cirúrgico da fibrilação atrial (FA). Objetivos: Estudar os resultados tardios da operação de Cox-Maze III, quanto à eficácia na manutenção de ritmo sinusal e taxas de mortalidade e acidente vascular cerebral (AVC). Métodos: Entre janeiro de 2006 a janeiro de 2013, 93 pacientes foram submetidos a operação de Cox-Maze III por corte e sutura associada a correção de cardiopatias estruturais. Avaliação do ritmo cardíaco ocorreu por Holter 24 horas. Taxas de sucesso da operação foram estudadas por métodos longitudinais e os preditores de recorrência por análise de regressão de Cox multivariada. Resultados: Foram excluídos 13 pacientes sobreviventes ao período intra-hospitalar cujo seguimento tardio não foi possível. Os 80 pacientes restantes tinham idade média de 49,9 ± 12 anos e 47 (58,75%) eram do sexo feminino. Acometimento da valva mitral ocorreu em 67 pacientes (83,7%). Valvopatia reumática ocorreu em 63 (78,7%). Setenta pacientes (87,5%) tinham fibrilação atrial persistente ou persistente de longa duração. O tempo médio de seguimento clínico com avaliação de Holter foi de 27,5 meses. Não houve óbitos intra-hospitalares. As taxas de manutenção de ritmo sinusal foram 88%, 85,1% e 80,6% aos 6 meses, 24 meses e 36 meses, respectivamente. Os preditores de recorrência tardia foram sexo feminino (RR 3,52; IC 95% 1,21-10,25; p = 0,02), doença arterial coronária (RR 4,73; IC 95% 1,37-16,36; p = 0,01) e maior diâmetro de átrio esquerdo (RR 1,05; IC 95% 1,01-1,09; p = 0,02). A sobrevida atuarial aos 12, 24 e 48 meses foi de 98,5% e as taxas atuariais livres de AVC nos mesmos períodos de 100%, 100% e 97,5%. Conclusões: A operação de Cox-Maze III, na nossa experiência, é eficaz na manutenção do ritmo sinusal, com baixíssimos índices de mortalidade e de AVC tardios.

Implantable cardioverter-defibrillators for treatment of sustained ventricular arrhythmias in patients with Chagas' heart disease: comparison with a control group treated with amiodarone alone.

AIMS: Evidence is inconclusive concerning the benefit of implantable cardioverter-defibrillators (ICDs) for secondary prevention of mortality in patients with Chagas' heart disease (ChHD). The aim of this study was to compare the outcomes of ChHD patients with life-threatening ventricular arrhythmias (VAs), who were treated either with ICD implantation plus amiodarone or with amiodarone alone. METHODS AND RESULTS: The ICD group [76 patients; 48 men; age, 57 ± 11 years; left ventricular ejection fraction (LVEF), 39 ± 12%] and the historical control group treated with amiodarone alone (28 patients; 18 men; age, 54 ± 10 years; LVEF, 41 ± 10%) had comparable baseline characteristics, except for a higher use of beta-blockers in the ICD group (P < 0.0001). Amiodarone was also used in 90% of the ICD group. Therapy with ICD plus amiodarone resulted in a 72% reduced risk of all-cause mortality (P = 0.007) and a 95% reduced risk of sudden death (P = 0.006) compared with amiodarone-only therapy. The survival benefit of ICD was greatest in patients with LVEF < 40% (P = 0.01) and was not significant in those with LVEF ≥ 40% (P = 0.15). Appropriate ICD therapies occurred in 72% of patients and the rates of interventions were similar across patients with LVEF < 40% and ≥40%. CONCLUSION: Compared with amiodarone-only therapy, ICD implantation plus amiodarone reduced the risk of all-cause mortality and sudden death in ChHD patients with life-threatening VAs. Patients with LVEF < 40% derived significantly more survival benefit from ICD therapy. The majority of ICD-treated patients received appropriate therapies regardless of the LV systolic function.

Predictors of mortality in patients with Chagas' cardiomyopathy and ventricular tachycardia not treated with implantable cardioverter-defibrillators.

BACKGROUND: The natural history of the arrhythmogenic form of Chagas' heart disease is not fully understood. METHODS: We assessed the outcome of 56 patients with Chagas' cardiomyopathy ([31 men]; mean age of 55 years; mean left ventricular ejection fraction [LVEF] 42%) presenting with either sustained ventricular tachycardia (VT) or nonsustained VT (NSVT), before therapy with implantable cardioverter-defibrillator was available at our center. RESULTS: Over a mean follow-up of 38 ± 16 months (range, 1-61 months), 16 patients (29%) died, 11 due to sudden cardiac death (SCD), and five from progressive heart failure. Survivors and nonsurvivors had comparable baseline characteristics, except for a lower LVEF (46 ± 7% vs 31 ± 9%, P < 0.001) and a higher New York Heart Association class (P = 0.003) in those who died during follow-up. Receiver-operator characteristic curve analysis showed that an LVEF cutoff value of 38% had the best accuracy for predicting all-cause mortality and an LVEF cutoff value of 40% had the best accuracy for prediction of SCD. Using the multivariate Cox regression analysis, LVEF < 40% was the only predictor of all-cause mortality (hazard ratio [HR] 12.22, 95% confidence interval [CI] 3.46-43.17, P = 0.0001) and SCD (HR 6.58, 95% CI 1.74-24.88, P = 0.005). CONCLUSIONS: Patients with Chagas' cardiomyopathy presenting with either sustained VT or NSVT run a major risk for mortality when had concomitant severe or even moderate LV systolic dysfunction.