Lista de Siglas/Abreviaturas 18 F-FDG – fluordesoxiglicose marcado com flúor-18 123 I-MIBG – meta-iodo-benzil-guanidina marcado com iodo-123 […] Diretriz da SBC sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas – 2023 Lista de Siglas/Abreviaturas 18 F-FDG – fluordesoxiglicose marcado com flúor-18 123 I-MIBG – meta-iodo-benzil-guanidina marcado com iodo-123 […] Diretriz da SBC sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas – 2023

Aims This study aimed to estimate the annual mortality risk and its determinants in chronic Chagas cardiomyopathy. Methods and results We conducted a systematic search in MEDLINE, Web of Science Core Collection, Embase, Cochrane Library, and LILACS. Longitudinal studies published between 1 January 1946 and 24 October 2018 were included. A random-effects meta-analysis using the death rate over the mean follow-up period in years was used to obtain pooled estimated annual mortality rates. Main outcomes were defined as all-cause mortality, including cardiovascular, non-cardiovascular, heart failure, stroke, and sudden cardiac deaths. A total of 5005 studies were screened for eligibility. A total of 52 longitudinal studies for chronic Chagas cardiomyopathy including 9569 patients and 2250 deaths were selected. The meta-analysis revealed an annual all-cause mortality rate of 7.9% [95% confidence interval (CI): 6.3–10.1; I² = 97.74%; T² = 0.70] among patients with chronic Chagas cardiomyopathy. The pooled estimated annual cardiovascular death rate was 6.3% (95% CI: 4.9–8.0; I² = 96.32%; T² = 0.52). The annual mortality rates for heart failure, sudden death, and stroke were 3.5%, 2.6%, and 0.4%, respectively. Meta-regression showed that low left ventricular ejection fraction (coefficient = −0.04; 95% CI: −0.07, −0.02; P = 0.001) was associated with an increased mortality risk. Subgroup analysis based on American Heart Association (AHA) classification revealed pooled estimate rates of 4.8%, 8.7%, 13.9%, and 22.4% (P < 0.001) for B1/B2, B2/C, C, and C/D stages of cardiomyopathy, respectively. Conclusions The annual mortality risk in chronic Chagas cardiomyopathy is substantial and primarily attributable to cardiovascular causes. This risk significantly increases in patients with low left ventricular ejection fraction and those classified as AHA stages C and C/D.

Chagas cardiomyopathy caused by infection with the intracellular parasite Trypanosoma cruzi is the most common and severe expression of human Chagas disease. Heart failure, systemic and pulmonary thromboembolism, arrhythmia, and sudden cardiac death are the principal clinical manifestations of Chagas cardiomyopathy. Ventricular arrhythmias contribute significantly to morbidity and mortality and are the major cause of sudden cardiac death. Significant gaps still exist in the understanding of the pathogenesis mechanisms underlying the arrhythmogenic manifestations of Chagas cardiomyopathy. This article will review the data from experimental studies and translate those findings to draw hypotheses about clinical observations. Human- and animal-based studies at molecular, cellular, tissue, and organ levels suggest 5 main pillars of remodeling caused by the interaction of host and parasite: immunologic, electrical, autonomic, microvascular, and contractile. Integrating these 5 remodeling processes will bring insights into the current knowledge in the field, highlighting some key features for future management of this arrhythmogenic disease.

Endemic in more than 20 countries, Chagas disease affects 6.3 million people worldwide, leading to 28,000 new infections and 7700 deaths each year. Previous meta-analyses on antiparasitic treatment need updates to encompass recent studies and to assess key clinically meaningful endpoints. This study aims to evaluate the impact of antitrypanosomal therapy in preventing or reducing disease progression and mortality in chronic Chagas disease. We performed a systematic review and meta-analysis of studies reporting the cardiovascular outcomes of antitrypanosomal therapy in patients with chronic Chagas disease. We searched Ovid Embase, Ovid MEDLINE, Ovid Global Health, Scopus, Web of Science Core Collection, Cochrane Library, PubMed, Google Scholar, and Virtual Health Library databases from inception to May 18, 2024. We included aggregated data from randomized controlled studies and observational reports (full articles and abstracts) featuring antiparasitic interventions with benznidazole or nifurtimox compared to a control group. Primary outcomes were electrocardiogram (ECG) changes, disease progression, cardiovascular death, and overall mortality. A customized risk of bias scale assessed the methodological quality of studies, and a random-effects model estimated the pooled risk ratios. This investigation was registered in PROSPERO (CRD42023495755). Out of 4666 reports screened, 23 met the pre-specified inclusion criteria (8972 participants). Compared to no treatment or placebo, antiparasitic treatment led to a reduction in i) ECG changes (17 studies, 4994 participants: risk ratio (RR): 0.48, 95% CI 0.36–0.66, p < 0.001; I² = 76.4%) with a number needed to treat (NNT) of 5; ii) disease progression (12 studies, 5722 participants: RR: 0.35, 95% CI 0.23–0.51, p < 0.001; I² = 72.4%) NNT of 6; iii) cardiovascular death (7 studies, 5662 participants: RR: 0.44, 95% CI 0.21–0.95, p = 0.04; I² = 50.5%) NNT of 22; and iv) overall mortality (10 studies, 7694 participants: RR: 0.54, 95% CI 0.34–0.87, p < 0.001; I² = 60%) NNT of 23. We found compelling evidence that antiparasitic treatment significantly reduces the risk of ECG changes, disease progression, cardiovascular death, and overall mortality in chronic Chagas disease. Although the quality of evidence ranges from low to intermediate, with considerable heterogeneity across studies, the potential benefits are substantial. These findings support the broader use of trypanocidal therapy in the management of Chagas disease, though further research remains necessary. This study had no funding source.