Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Chronic Chagas cardiomyopathy (CCC), the most severe form of target organ involvement in Chagas disease, is characterized by a complex pathophysiology and a unique phenotype that differentiates it from other cardiomyopathies, highlighting its worse prognosis compared to other aetiologies of heart failure. The three pathophysiological mechanisms with the largest impact on this differential mortality include rapidly progressive heart failure, a high incidence of stroke, and a high burden of ventricular arrhythmias. However, despite significant advances in understanding the unique molecular circuits underlying these mechanisms, the new knowledge acquired has not been efficiently translated into specific diagnostic and therapeutic approaches for this unique cardiomyopathy. The lack of dedicated clinical trials and the limited CCC‐specific risk stratification tools available are evidence of this reality. This review aims to provide an updated perspective of the evidence and pathophysiological mechanisms associated with the higher mortality observed in CCC compared to other cardiomyopathies and highlight opportunities in the diagnostic and therapeutic approaches of the disease.

中文翻译：

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慢性恰加斯心肌病高死亡率背后的机制：揭开三头怪物的面纱


查加斯病是一种被忽视的热带疾病，由寄生虫克氏锥虫引起。慢性恰加斯心肌病（CCC）是恰加斯病靶器官受累最严重的形式，其特点是复杂的病理生理学和独特的表型，使其与其他心肌病区分开来，突显其与其他心力衰竭病因相比的预后较差。对这种差异死亡率影响最大的三种病理生理机制包括快速进展的心力衰竭、中风的高发病率和室性心律失常的高负担。然而，尽管在理解这些机制背后的独特分子回路方面取得了重大进展，但所获得的新知识尚未有效转化为这种独特心肌病的具体诊断和治疗方法。缺乏专门的临床试验和可用的 CCC 特定风险分层工具有限就是这一现实的证据。本综述旨在提供与 CCC 与其他心肌病相比较高死亡率相关的证据和病理生理学机制的最新观点，并强调该疾病的诊断和治疗方法的机会。