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Sex Differences in Chagas Cardiomyopathy: a Comprehensive Review
Antonio de Padua Mansur1, Edecio Cunha-Neto2,3, Reinaldo Bulgarelli Bestetti4
1Serviço de Prevencao, Cardiopatia na Mulher e Reabilitação Cardiovascular, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, SP, Brazil. apmansur@yahoo.com.
Insights
Men with Chagas cardiomyopathy experience severe heart failure (HF) more often. Women show milder HF phenotypes and slower progression, suggesting a need for sex-specific Chagas cardiomyopathy management.
Area of Science:
- Cardiology
- Immunology
- Genetics
Background:
- Chagas cardiomyopathy (CCC) is a primary cause of heart failure (HF) in Latin America.
- Sex-specific differences in HF presentation and outcomes in CCC are not well understood.
Purpose of the Study:
- To review current knowledge on clinical manifestations, HF phenotypes, and molecular mechanisms in women and men with CCC.
- To highlight sex-based disparities in Chagas cardiomyopathy.
Main Methods:
- Literature review of clinical manifestations, HF phenotypes, and molecular mechanisms in CCC.
- Analysis of sex-specific differences in disease presentation, progression, and molecular signatures.
Main Results:
- Men with CCC more frequently present with severe HF, arrhythmias, and sudden cardiac death.
- Women with CCC often exhibit milder HF phenotypes, slower progression, and varied HF subtypes (HFrEF, HFmrEF, HFpEF).
- Molecular studies reveal distinct inflammatory profiles: males show Th1 signatures, while females exhibit Th2 and Treg enrichment.
Conclusions:
- Significant sex-based differences exist in CCC presentation, HF phenotypes, and underlying molecular mechanisms.
- Hormonal and immune factors may contribute to milder disease progression in women.
- Sex-specific evaluation and management strategies are crucial for optimizing CCC care.
Purpose Of 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.
Recent Findings:
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.
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