Survival and reactivation risk after heart transplantation in Chagas heart disease: a systematic review and individual patient data meta-analysis

Introduction Chagas heart disease (ChHD) is a leading trigger of end-stage heart failure in Latin America, with heart transplantation as its final treatment. Large-scale individual patient data (IPD) evidence on transplant immunosuppression, parasite reactivation and long-term prognosis remains scarce. Methods We conducted an IPD meta-analysis by retrieving eligible studies up to October 4, 2025, extracting individual clinical data and adopting one-stage IPD and Cox regression analyses. Results Sixteen studies with 305 ChHD transplant recipients were enrolled. Male sex was associated with increased risks of complications, reactivation, and death in observational analyses. Similarly, AZA exposure was associated with a lower risk of reactivation, and MMF exposure was associated with a lower risk of death. Notably, exploratory historical comparison suggests relatively favourable long-term survival among selected ChHD transplant recipients relative to published cohorts of other cardiomyopathies, though this finding cannot be adequately adjusted for key patient-level confounders. Discussion These associations are subject to confounding by indication, transplantation era, monitoring strategies, and switching-time bias. They therefore cannot be interpreted as causal treatment effects, nor can they establish that any one regimen is superior. In selected patients with end-stage Chagas heart disease, heart transplantation is a feasible treatment option associated with acceptable long-term survival outcomes. Systematic Review Registration PROSPERO [CRD420251163696].