Clinical Progression of Cardiac Chronic Trypanosoma cruzi Infection in a Long-Term Prospective Cohort from Rural Colombia

Chronic <i>Trypanosoma cruzi</i> infection remains a major cause of preventable cardiomyopathy in Latin America, yet prospective data from endemic rural populations after the interruption of domestic transmission are limited. This study characterizes the long-term clinical evolution, treatment response, and cardiovascular outcomes of 80 adults with confirmed chronic infection from Mogotes, Santander, Colombia. Participants were followed from 2015 to 2023 by means of standardized clinical, electrocardiographic, echocardiographic, serological, and qPCR evaluations. The primary outcome was progression from the indeterminate to the cardiac form; secondary outcomes included worsening to advanced cardiomyopathy and cardiovascular events. During 422 person-years of follow-up (median 61.5 months), 14 participants (17.5%) experienced clinical progression (3.3 per 100 person-years) and seven (9%) died (1.7 per 100 person-years). Benznidazole treatment was initiated in 42 participants and completed by 34 (81%); only 4 of 34 (12%) remained qPCR-positive after one year, compared with 21% among untreated individuals. Progression from the indeterminate form occurred in one participant (0.7 per 100 person-years), whereas deterioration clustered among those with baseline cardiomyopathy. Despite low mortality, stage-dependent progression persisted, highlighting the need for early diagnosis, treatment adherence, and sustained molecular and cardiac monitoring in post-certification settings. These findings provide rare longitudinal evidence on chronic <i>T. cruzi</i> infection under real-world endemic conditions.