Sex Differences in Chagas Cardiomyopathy: a Comprehensive Review

Chagas cardiomyopathy (CCC) is a major cause of heart failure (HF) in Latin America, yet sex-specific differences in HF presentation and outcomes remain underexplored. This review summarizes current knowledge on clinical manifestations, HF phenotypes, and molecular mechanisms in women and men with CCC.

Men with CCC more frequently present with severe HF, arrhythmias, and sudden cardiac death, whereas women often exhibit nonspecific symptoms such as fatigue and palpitations. HF prevalence in women is variable, with some cohorts showing lower left ventricular systolic dysfunction in women. Among women with CCC-HF, 41% have HFrEF, 20% HFmrEF, and 39% HFpEF. Dyspnea affects 29% of women, approximately half the male rate. Comorbidities are generally similar, though chronic kidney disease is less common in women. Molecular and transcriptomic studies indicate that males exhibit stronger Th1 inflammatory signatures, while females show enrichment of Th2 and Treg cells, correlating with disease severity. Women with CCC tend to experience milder HF phenotypes and slower progression, potentially due to hormonal and immune-mediated mechanisms, highlighting the need for sex-specific evaluation and management strategies in CCC.