Predictors of cardiomyopathy progression in a Chagas disease cohort in Bolivia

玻利维亚恰加斯病队列中心肌病进展的预测因子

• 批准号: 9208732
• 负责人: ROBERT H GILMAN
• 金额: $ 58.74万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-15 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9208732
• 关键词: Acute; Adult; Age; Algorithms; Americas; Appearance; Benznidazole; Biological Markers; Bolivia; Bolivian; Brain natriuretic peptide; Cardiac; Cardiomyopathies; Categories; Cessation of life; Chagas Cardiomyopathy; Chagas Disease; Characteristics; Child; Chronic; Chronic Phase; Cicatrix; Cities; Classification; Clinical; Clinical Trials; Cohort Studies; Communities; Congestive Heart Failure; Country; Data; Development; Dilated Cardiomyopathy; Discrimination; Disease; District Hospitals; Electrocardiogram; Electrophysiology (science); Epidemiology; Exposure to; Fibrosis; Frequencies; Functional disorder; Future; Gelatinase A; Grant; Health; Heart Diseases; High Prevalence; Hospitals; Human; Individual; Infection; Inflammatory; Latin America; Life; Longitudinal Studies; Matrix Metalloproteinase Inhibitor; Matrix Metalloproteinases; Methods; Morbidity - disease rate; Myocarditis; N-terminal; Necrosis; Outcome Measure; Pacemakers; Parasitemia; Parasitic Diseases; Participant; Pathogenesis; Pathogenicity; Patients; Pattern; Peptides; Peripheral; Pharmaceutical Preparations; Play; Population; Predictive Value; Prevalence; Probability; Process; Proteins; Public Hospitals; Recruitment Activity; Regimen; Reporting; Resolution; Resources; Risk; Role; Serum; Severities; Sinus; South America; Structural defect; Structure; Suggestion; Surveys; System; TGFB1 gene; Testing; Time; Tissues; Transforming Growth Factors; Trees; Troponin T; Trypanosoma cruzi; Type I Procollagen; United States; Validation; Ventricular Arrhythmia; animal data; base; biomarker development; cohort; connective tissue growth factor; coronary fibrosis; cost; deep sequencing; follow-up; heart disease risk; high risk; indexing; mortality; potential biomarker; prevent; programs; public health relevance; response; saluretic; standard of care; superinfection; tool; vector; virtual

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.

描述（由申请人提供）：尽管在控制锥蝽媒介方面取得了进展，玻利维亚仍然是世界上克氏锥虫感染率最高的国家。主要临床表现是恰加斯心肌病，其特征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伴充血性心力衰竭。国家计划历来只治疗患有恰加斯病的儿童，但在过去 10 年里，成人治疗的动力显着增长，这是基于不断增长的患者需求和观察数据表明，即使是早期心脏病患者的治疗，也可以减少恰加斯心脏病的进展，并可能降低死亡率。尽管如此，成人治疗仍将超出玻利维亚等国家的资源范围，因为没有有效的算法来针对心脏病高危人群。可靠的心脏风险早期指标将使治疗能够针对未来发病和死亡可能性最高的 20% 至 30% 的感染者。检测早期恰加斯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，例如因心脏病而释放的 B 型利尿钠肽等物质，或细胞水平上参与心脏发病机制的转化生长因子-β1 等物质。我们建议在一项队列研究中同时检查多个类别的生物标志物，以单独和组合地全面评估其相对效用，该研究招募自（1）高流行村庄，其中> 95％的成年人患有克氏锥虫感染，并且17％> 30岁的感染者具有恰加斯心肌病特征的心电图异常，（2）圣塔市的一家大型公立医院 Cruz 地区，我们预计超过 50% 的心脏病患者患有恰加斯心脏病，并且 (3) 一家地区医院位于与上述社区相同的高流行区。主要结果指标是 4 年随访期内恰加斯心肌病的进展情况。由于感染率极高，该人群非常适合评估生物标志物与早期恰加斯心肌病之间的关联。