Predictors of cardiomyopathy progression in a Chagas disease cohort in Bolivia

描述（由申请人提供）：尽管在控制锥虫病媒方面取得了进展，玻利维亚仍然是世界上克氏锥虫感染率最高的国家。主要临床表现为查加斯心肌病，其特点是慢性炎症过程导致传导系统异常、室性心律失常、窦房结功能障碍和进行性扩张型心肌病合并充血性心力衰竭。历史上，国家项目只治疗患有恰加斯病的儿童，但在过去10年里，基于不断增长的患者需求和观察数据，成人治疗的动力有了显著增长，这些数据表明，即使是对早期心脏疾病的患者进行治疗，也可以减少恰加斯病的进展，甚至可能降低死亡率。然而，成人治疗仍然超出玻利维亚等国家的资源范围，没有针对心脏病高风险人群的有效算法。一个可靠的心脏风险早期指标将使治疗针对20%至30%的感染个体，这些个体未来发病率和死亡率的可能性最高。检测早期恰加斯心脏病的生物标志物可能反映了心脏结构和功能的早期变化，如心脏病反应中释放的b型利钠肽或细胞水平上参与心脏发病的转化生长因子- β 1等物质。我们建议同时检查多个类别的生物标志物，以便全面评估它们的相对效用，单独和组合，在一项队列研究中，从(1)高流行村庄招募，其中95%的成年人患有克氏弓形虫感染，17%的感染者患有30岁以上的恰加斯心肌病特征的心电图异常。(2)圣克鲁斯市的一家大型公立医院，我们预计有50%的心脏病患者患有恰加斯心脏病；(3)与上述社区位于同一高流行区的一家地区医院。主要结果测量将是在4年随访期间查加斯心肌病的进展。由于感染的患病率非常高，这一人群将是评估生物标志物与早期恰加斯心肌病之间关系的理想人群。

DESCRIPTION (provided by applicant): Despite progress in the control of the triatomine vectors, Bolivia remains the country with the highest Trypanosoma cruzi infection prevalence in the world. The major clinical manifestation is Chagas cardiomyopathy, characterized by a chronic inflammatory process leading to conduction system abnormalities, ventricular arrhythmias, sinus node dysfunction and progressive dilated cardiomyopathy with congestive heart failure. National programs have historically only treated children with Chagas disease, but the impetus for adult treatment has grown significantly in the last 10 years, based on growing patient demand and observational data suggesting that treatment, even in patients with early cardiac morbidity decreases the progression of Chagas heart disease and possibly also mortality. Nevertheless, adult treatment will remain beyond the resources of countries like Bolivia, without an effective algorithm to target those at high risk of heart disease. A reliable early indicator of cardiac risk would allow treatment to be targeted to the 20 to 30% of infected individuals with the highest likelihood of future morbidity and mortality. Biomarkers to detect early Chagas heart disease may reflect early changes in cardiac structure and function, substances such as B-type natriuretic peptide released in response to cardiac disease or a substance such as transforming growth factor- beta1 involved in cardiac pathogenesis at the cellular level. We propose to examine biomarkers in multiple categories simultaneously to allow a comprehensive assessment of their relative utility, individually and in combination, in a cohort study recruited from (1) hyperendemic villages where >95% of adults have T. cruzi infection and 17% of infected individuals > 30 years have electrocardiographic abnormalities characteristic of Chagas cardiomyopathy, (2) a large public hospital in the city of Santa Cruz where we expect >50% of cardiac patients to have Chagas heart disease and (3) a district hospital in the same hyperendemic zone as the communities mentioned above. The major outcome measure will be progression of Chagas cardiomyopathy over a 4-year follow-up period. Because of the extraordinarily high prevalence of infection, this population will be ideal for assessing associations between biomarkers and early Chagas cardiomyopathy.