Predictors of cardiomyopathy progression in a Chagas disease cohort in Bolivia

描述(申请人提供)：尽管玻利维亚在控制三聚氰胺媒介方面取得了进展，但它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Chagas心肌病，以慢性炎症过程为特征，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并充血性心力衰竭。从历史上看，国家项目只治疗查加斯病的儿童，但在过去10年里，成人治疗的动力显著增强，因为不断增长的患者需求和观察数据表明，治疗，即使是对早期心脏疾病的患者，也会减缓查加斯心脏病的进展，可能还会降低死亡率。然而，成人治疗仍将超出玻利维亚等国家的资源范围，没有针对心脏病高危人群的有效算法。一个可靠的心脏风险早期指标将使治疗能够针对未来发病率和死亡率最高的20%至30%的感染者。检测查加斯早期心脏病的生物标志物可能反映心脏结构和功能的早期变化，如因心脏病而释放的B型利钠肽等物质，或在细胞水平上参与心脏发病的转化生长因子-β1等物质。我们建议同时检测多个类别的生物标记物，以便在一项队列研究中对它们的相对效用进行全面评估，该研究从(1)高度流行的村庄招募，其中95%的成年人患有弓形虫感染，17%的感染者患有查加斯心肌病的心电图异常；(2)圣克鲁斯市的一家大型公立医院，在那里我们预计&>50%的心脏病患者患有查加斯心脏病；(3)与上述社区处于同一高度流行区的地区医院。主要的结果衡量标准将是查加斯心肌病在4年随访期内的进展情况。由于感染的发病率非常高，这一人群将是评估生物标记物与早期查加斯心肌病之间关联的理想人群。

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.