ABSTRACT
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.
ABSTRACT
Abstract Background: Sudden cardiac death is the most frequent death mechanism in Chagas disease, responsible for 55% to 65% of the deaths of patients with chronic Chagas cardiomyopathy (CCC). The most often involved electrophysiological mechanisms are ventricular tachycardia and ventricular fibrillation. The implantable cardioverter defibrillator (ICD) has a beneficial role in preventing sudden death due to malignant ventricular arrhythmias, and, thus the correct identification of patients at risk is required. The association of microvolt T-wave alternans (MTWA) with the appearance of ventricular arrhythmias has been assessed in different heart diseases. The role of MTWA is mostly unknown in patients with CCC. Objectives: To evaluate the association between MTWA and the occurrence of malignant ventricular arrhythmias in patients with CCC. Method: This is a case-control study including patients with CCC and ICD, with history of malignant ventricular arrhythmias (case group), and patients with CCC and no history of those arrhythmias (control group). The MTWA test results were classified as negative and non-negative (positive and indeterminate). The significance level adopted was a = 0.05. Results: We recruited 96 patients, 45 cases (46.8%) and 51 controls (53.1%). The MTWA test was non-negative in 36/45 cases (80%) and 15/51 controls (29.4%) [OR = 9.60 (95%CI: 3.41 - 27.93)]. After adjustment for known confounding factors in a logistic regression model, the non-negative result continued to be associated with malignant ventricular arrhythmias [OR = 5.17 (95%CI: 1.05 - 25.51)]. Conclusion: Patients with CCC and history of malignant ventricular arrhythmias more often have a non-negative MTWA test as compared to patients with no history of arrhythmia.
Resumo Fundamento: A morte súbita cardíaca é o mecanismo de morte mais comum na doença de Chagas, responsável pelo óbito de 55% a 65% dos pacientes com cardiomiopatia chagásica crônica (CCC). Os mecanismos mais frequentemente envolvidos são as taquiarritmias ventriculares. O cardioversor-desfibrilador implantável (CDI) apresenta impacto na redução da mortalidade por arritmias ventriculares e faz-se necessária a correta identificação de pacientes sob risco. A associação de microalternância de onda T (MTWA) com o aparecimento de arritmias ventriculares foi avaliada em diferentes cardiopatias através de um teste. O papel da MTWA na identificação de pacientes sob risco na CCC permanece incerto. Objetivo: Avaliar a associação entre MTWA e a ocorrência de arritmias ventriculares malignas na CCC. Método: Trata-se de um estudo caso-controle, que incluiu pacientes com CCC em uso de CDI, com história prévia de arritmias ventriculares malignas (casos) ou sem história prévia (controles). Os resultados do teste foram classificados em negativo e não negativo (positivo e indeterminado). O nível de significância foi a = 0,05. Resultado: Foram recrutados 96 pacientes, 45 no grupo caso (46,8%) e 51 no grupo controle (53,1%). O teste de MTWA apresentou resultado não negativo em 36/45 pacientes no grupo caso (80%) e 15/51 no grupo controle (29,4%), OR = 9,60 (IC95%: 3,41 - 27,93). Após ajuste para fatores de confusão num modelo de regressão logística, o resultado não negativo continuou associado à presença de arritmias ventriculares malignas, com OR = 5,17 (IC95%: 1,05 - 25,51). Conclusão: Na CCC, pacientes com história de arritmia ventricular maligna apresentam maior frequência de teste de MTWA não negativo quando comparados a pacientes sem ocorrência prévia de arritmias.
Subject(s)
Humans , Male , Female , Middle Aged , Arrhythmias, Cardiac/etiology , Death, Sudden, Cardiac/etiology , Chagas Disease/complications , Arrhythmias, Cardiac/physiopathology , Case-Control Studies , Survival Analysis , Risk Factors , Death, Sudden, Cardiac/prevention & control , Chagas Disease/physiopathology , Tachycardia, Ventricular/etiology , Defibrillators, Implantable , ElectrocardiographyABSTRACT
BACKGROUND: Sudden cardiac death is the most frequent death mechanism in Chagas disease, responsible for 55% to 65% of the deaths of patients with chronic Chagas cardiomyopathy (CCC). The most often involved electrophysiological mechanisms are ventricular tachycardia and ventricular fibrillation. The implantable cardioverter defibrillator (ICD) has a beneficial role in preventing sudden death due to malignant ventricular arrhythmias, and, thus the correct identification of patients at risk is required. The association of microvolt T-wave alternans (MTWA) with the appearance of ventricular arrhythmias has been assessed in different heart diseases. The role of MTWA is mostly unknown in patients with CCC. OBJECTIVES: To evaluate the association between MTWA and the occurrence of malignant ventricular arrhythmias in patients with CCC. METHOD: This is a case-control study including patients with CCC and ICD, with history of malignant ventricular arrhythmias (case group), and patients with CCC and no history of those arrhythmias (control group). The MTWA test results were classified as negative and non-negative (positive and indeterminate). The significance level adopted was a = 0.05. RESULTS: We recruited 96 patients, 45 cases (46.8%) and 51 controls (53.1%). The MTWA test was non-negative in 36/45 cases (80%) and 15/51 controls (29.4%) [OR = 9.60 (95%CI: 3.41 - 27.93)]. After adjustment for known confounding factors in a logistic regression model, the non-negative result continued to be associated with malignant ventricular arrhythmias [OR = 5.17 (95%CI: 1.05 - 25.51)]. CONCLUSION: Patients with CCC and history of malignant ventricular arrhythmias more often have a non-negative MTWA test as compared to patients with no history of arrhythmia.
Subject(s)
Arrhythmias, Cardiac/etiology , Chagas Disease/complications , Death, Sudden, Cardiac/etiology , Arrhythmias, Cardiac/physiopathology , Case-Control Studies , Chagas Disease/physiopathology , Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Electrocardiography , Female , Humans , Male , Middle Aged , Risk Factors , Survival Analysis , Tachycardia, Ventricular/etiologyABSTRACT
BACKGROUND: Chagas disease (ChD) may lead to life-threatening heart disease, including malignant ventricular arrhythmias. The use of implantable cardioverter defibrillators (ICDs) has become the main therapeutic strategy for secondary prevention of SCD in Chagas disease (ChD). Microvolt T-wave alternans (MTWA) is a direct measure of ventricular repolarization instability and has emerged as a potentially useful way of determining arrhythmia vulnerability. However, this methodology has not been evaluated in patients with ChD. OBJECTIVE: To evaluate the predictive value of MTWA testing for appropriate therapy or death in ChD patients with ICDs. METHODS: This prospective study included consecutive patients who received ICD implantations in a Brazilian tertiary referral center. RESULTS: Seventy-two patients were followed for a median time of 422 (range 294-642) days. Thirty-three patients had ChD. The MTWA was non-negative (positive or indeterminate) in 27 (81.8%) of ChD patients. The combined primary outcome (appropriate ICD therapy or death) occurred in 29 patients (40.3%); 17 out 33 ChD patients presented the primary outcome. There was a statistically significant difference in event-free survival between ChD patients with negative and non-negative MTWA results (p=0.02). Non-negative MTWA tests nearly triple the risk of appropriate ICD therapy or death (HR=2.7, 95% CI: 1.7-4.4, p=0.01) in patients with ChD and was the only variable associated with outcomes. The sensitivity and the negative predictive value was 100% in ChD patients. CONCLUSIONS: MTWA may be useful in recognizing high-risk ICD patients who may require adjunctive therapies with antiarrhythmic drugs or catheter ablation.
Subject(s)
Arrhythmias, Cardiac , Chagas Disease , Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Electrocardiography/methods , Aged , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/prevention & control , Brazil/epidemiology , Chagas Disease/complications , Chagas Disease/diagnosis , Chagas Disease/mortality , Chagas Disease/therapy , Disease-Free Survival , Electric Countershock/instrumentation , Electric Countershock/methods , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Assessment/methodsSubject(s)
Chagas Cardiomyopathy/physiopathology , Electrocardiography , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle AgedABSTRACT
Sudden death is one of the most characteristic phenomena of Chagas disease, and approximately one-third of infected patients develop life-threatening heart disease, including malignant ventricular arrhythmias. Fibrotic lesions secondary to chronic cardiomyopathy produce arrhythmogenic substrates that lead to the appearance and maintenance of ventricular arrhythmias. The objective of this study is to discuss the main clinical and epidemiological aspects of ventricular arrhythmias in Chagas disease, the specific workups and treatments for these abnormalities, and the breakthroughs needed to determine a more effective approach to these arrhythmias. A literature review was performed via a search of the PubMed database from 1965 to May 31, 2014 for studies of patients with Chagas disease. Clinical management of patients with chronic Chagas disease begins with proper clinical stratification and the identification of individuals at a higher risk of sudden cardiac death. Once a patient develops malignant ventricular arrhythmia, the therapeutic approach aims to prevent the recurrence of arrhythmias and sudden cardiac death by the use of implantable cardioverter defibrillators, antiarrhythmic drugs, or both. In select cases, invasive ablation of the reentrant circuit causing tachycardia may be useful. Ventricular arrhythmias are important manifestations of Chagas cardiomyopathy. This review highlights the absence of high-quality evidence regarding the treatment of ventricular arrhythmias in Chagas disease. Recognizing high-risk patients who require specific therapies, especially invasive procedures such as the implantation of cardioverter defibrillators and ablative approaches, is a major challenge in clinical practice.
Subject(s)
Chagas Cardiomyopathy/complications , Death, Sudden, Cardiac/prevention & control , Tachycardia, Ventricular/etiology , Echocardiography , Electrocardiography , Humans , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/therapyABSTRACT
Sudden death is one of the most characteristic phenomena of Chagas disease, and approximately one-third of infected patients develop life-threatening heart disease, including malignant ventricular arrhythmias. Fibrotic lesions secondary to chronic cardiomyopathy produce arrhythmogenic substrates that lead to the appearance and maintenance of ventricular arrhythmias. The objective of this study is to discuss the main clinical and epidemiological aspects of ventricular arrhythmias in Chagas disease, the specific workups and treatments for these abnormalities, and the breakthroughs needed to determine a more effective approach to these arrhythmias. A literature review was performed via a search of the PubMed database from 1965 to May 31, 2014 for studies of patients with Chagas disease. Clinical management of patients with chronic Chagas disease begins with proper clinical stratification and the identification of individuals at a higher risk of sudden cardiac death. Once a patient develops malignant ventricular arrhythmia, the therapeutic approach aims to prevent the recurrence of arrhythmias and sudden cardiac death by the use of implantable cardioverter defibrillators, antiarrhythmic drugs, or both. In select cases, invasive ablation of the reentrant circuit causing tachycardia may be useful. Ventricular arrhythmias are important manifestations of Chagas cardiomyopathy. This review highlights the absence of high-quality evidence regarding the treatment of ventricular arrhythmias in Chagas disease. Recognizing high-risk patients who require specific therapies, especially invasive procedures such as the implantation of cardioverter defibrillators and ablative approaches, is a major challenge in clinical practice.
Subject(s)
Humans , Aging/genetics , Longevity/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study , GenotypeABSTRACT
AIMS: Implantable cardioverter-defibrillators (ICDs) are now a first-line option for prevention of sudden death in Chagas disease (ChD). However, efficacy and safety of ICD treatment in ChD remains controversial. The aim of our study was to compare clinical outcome after ICD implantation in ChD and non-ChD patients. METHODS AND RESULTS: The study population consists of patients who received ICD implantation in a tertiary Reference Center for ChD in Brazil. The primary endpoint of the study was appropriate therapy (appropriate shocks or anti-tachycardia pacing); the secondary endpoint was the event-free survival defined as absence of death or appropriate therapy. One hundred and thirty-five [corrected] patients were followed for the median time of 266 days. Sixty-five patients had ChD. Appropriate ICD therapy occurred in 32 (49.2%) ChD and in 19 (27.1%) non-ChD patients (P=0.005). Ventricular tachycardia occurred in 27 (42%) ChD and in 16 (23%) non-ChD (P = 0.01) patients. There was a statistically significant difference in event-free survival between the group of patients with and without ChD (P=0.004). The median event-free survival was 230 days (95% confidence interval, CI: 113-347) in patients with ChD and 549 days (95% CI: 412-687) in non-ChD patients. Chagas disease double the risk of the patient to have appropriate therapy (hazard ratio, HR = 2.2, 95% CI = 1.2-4.3, P = 0.02) and appropriate therapy or death (HR = 2.2, 95% CI = 1.2-4.2, P = 0.01) in multivariate analysis. There were 16 deaths (11.8%) with 8 deaths in each group and five inappropriate shocks (3.7%) with one in ChD patients (1.6%). CONCLUSION: The higher frequency of appropriate ICD therapy and the shorter event-free survival in ChD patients are consistent with the presence of an arrhythmogenic substrate that characterizes this cardiomyopathy.
Subject(s)
Arrhythmias, Cardiac/prevention & control , Chagas Cardiomyopathy/therapy , Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Electric Countershock/instrumentation , Aged , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/mortality , Brazil , Chagas Cardiomyopathy/complications , Chagas Cardiomyopathy/diagnosis , Chagas Cardiomyopathy/mortality , Death, Sudden, Cardiac/etiology , Disease-Free Survival , Electric Countershock/adverse effects , Electric Countershock/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Retrospective Studies , Risk Factors , Tertiary Care Centers , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Clinical history and exercise testing (ET) are the main methods used to screen for coronary artery disease (CAD). Correct interpretation of such data is essential in determining diagnostic and treatment strategies. OBJECTIVE: To assess the diagnostic value of stable angina (SA) and ET in patients with suspected CAD undergoing coronary angiography and to compare results between the sexes. METHODS: We assessed 62 patients undergoing coronary angiography; ET was performed in 54 of them, being considered positive for ischemia in cases of ST-segment depression of > or =1 mm. The coronary angiograms were analyzed by two observers and patients were divided into two groups depending on the severity of CAD: Group 1: > or =70% stenosis (n=26), and Group 2: <70% stenosis (n=36). RESULTS: The patients' mean age was 58+/-9 years, and 55% were male. SA was found in 24% of cases and ET was positive for ischemia in 53%. SA showed a sensitivity of 46.1%, specificity 91.7%, positive predictive value (PPV) 80%, negative predictive value (NPV) 70%, positive likelihood ratio (LR+) 5.1 and negative likelihood ratio (LR-) 0.6, while the corresponding results for ET were sensitivity of 70.8%, specificity 60%, PPV 59%, NPV 72%, LR+ 1.75 and LR- 0.5. SA was shown to have a greater NPV in women, and the LR+ was also significantly higher in women. CONCLUSION: SA was shown to be a good diagnostic marker, with high specificity and PPV. The greater NPV and LR+ in women was shown to be superior for post-test prediction of angina. ET results were similar for both sexes and showed similar sensitivity and specificity to that reported in the literature.
