Risk Factors for Progression to Chronic Chagas Cardiomyopathy: A Systematic Review and Meta-Analysis

Abstract

Approximately one-third of people with chronic Trypanosoma cruzi infection develop Chagas cardiomyopathy, which carries a poor prognosis. Accurate prediction of which individuals will go on to develop Chagas cardiomyopathy remains elusive. We performed a systematic review of literature comparing characteristics of individuals with chronic Chagas disease with or without evidence of cardiomyopathy. Studies were not excluded on the basis of language or publication date. Our review yielded a total of 311 relevant publications. We further examined the subset of 170 studies with data regarding individual age, sex, or parasite load. A meta-analysis of 106 eligible studies indicated that male sex was associated with having Chagas cardiomyopathy (Hedge’s g: 1.56, 95% CI: 1.07–2.04), and a meta-analysis of 91 eligible studies indicated that older age was associated with having Chagas cardiomyopathy (Hedge’s g: 0.66, 95% CI: 0.41–0.91). A meta-analysis of four eligible studies did not find an association between parasite load and disease state. This study provides the first systematic review to assess whether age, sex, and parasite load are associated with Chagas cardiomyopathy. Our findings suggest that older and male patients with Chagas disease are more likely to have cardiomyopathy, although we are unable to identify causal relationships due to the high heterogeneity and predominantly retrospective study designs in the current literature. Prospective, multidecade studies are needed to better characterize the clinical course of Chagas disease and identify risk factors for progression to Chagas cardiomyopathy.

Diagnosis and management of chagasic cardiomyopathy patients in several institutions in Argentina

“…In the analysis of risk factors and comorbidities, our study shows similar results to those registered in other studies of individuals with PMC. (Freitas Lidani et al, 2020;Cutshaw et al, 2023). Hypertension was observed in 69.5% of the patients in this study, a similar percentage to that found in the CONAREC XII registry (Perna et al, 2015;Assuncão et al, 2016), where 69.3% had heart failure.…”

Persistent Biofluid Small-Molecule Alterations Induced by Trypanosoma cruzi Infection Are Not Restored by Parasite Elimination

“…52 This could be due to the use of different mouse and parasite strains, 52 but may also reflect the lack of improvements of functional and survival outcomes in late-stage patient treatment, 7 even in cases of parasitological cure, and the disconnect between parasite burden and symptomatic vs asymptomatic chronic infection. 57 Importantly, our urine results concur with analysis of cardiac tissue in an independent infection model, which likewise showed only minor and incomplete metabolic restoration and functional restoration 56 days postbenznidazole treatment, even with successful parasite elimination. 56 As such, our method could represent a quick and noninvasive method to identify compounds with superior efficacy to benznidazole though this will need to be validated in additional animal models.…”

“…This contrasts with acute-stage benznidazole treatment, which restored the plasma and heart metabolome . This could be due to the use of different mouse and parasite strains, but may also reflect the lack of improvements of functional and survival outcomes in late-stage patient treatment, even in cases of parasitological cure, and the disconnect between parasite burden and symptomatic vs asymptomatic chronic infection . Importantly, our urine results concur with analysis of cardiac tissue in an independent infection model, which likewise showed only minor and incomplete metabolic restoration and functional restoration 56 days postbenznidazole treatment, even with successful parasite elimination .…”

Persistent biofluid small molecule alterations induced byTrypanosoma cruziinfection are not restored by antiparasitic treatment

“…This contrasts with acute-stage benznidazole treatment, which restored the plasma and heart metabolome 42 . This could be due to the use of different mouse and parasite strains 42 , but may also reflect the lack of improvements of clinical outcomes in late-stage patient treatment 7 and the disconnect between parasite burden and symptomatic vs asymptomatic chronic infection 46 . Importantly, our urine results concur with analysis of cardiac tissue in an independent infection model, which likewise showed only minor and incomplete metabolic restoration 56 days post-benznidazole treatment 47 .…”