Cardioembolic stroke in Chagas cardiomyopathy: the interplay between apical aneurysm, left ventricular thrombus and clinical outcomes

Objective Apical aneurysm is a hallmark of Chagas cardiomyopathy (CCM) and has long been implicated in thromboembolic complications. However, its independent contribution to cardioembolic (CE) stroke and the mechanisms underlying this association remain incompletely understood. This study evaluated the association between apical aneurysm and CE stroke and assessed the prognostic implications of CE stroke in patients with CCM. Methods In this prospective cohort study, 518 patients with confirmed CCM were enrolled at a tertiary referral centre between 2007 and 2022. Baseline evaluation included clinical assessment, electrocardiography and echocardiography. Ischaemic stroke subtype was classified using the Causative Classification System. Logistic regression analyses examined factors associated with CE stroke. Genetic matching was used to assess the association between apical aneurysm and CE stroke while causal mediation analysis evaluated the contribution of left ventricular (LV) thrombus. Cox proportional hazards models assessed factors associated with all-cause mortality or heart transplantation. Results At enrolment, 73 patients (14.1%) had a history of CE stroke. In multivariable analyses, New York Heart Association (NYHA) functional class III/IV, lower LV ejection fraction and LV thrombus were independently associated with prior CE stroke, whereas apical aneurysm was not. However, matched analyses demonstrated a significant association between apical aneurysm and CE stroke, of which 63.3% was mediated through LV thrombus formation. During a mean follow-up of 4.9 years, 174 patients died and 22 underwent heart transplantation. NYHA functional class III/IV, right-sided heart failure, left atrial enlargement and lower LV ejection fraction were independently associated with the composite outcome of death or heart transplantation, whereas neither prior CE stroke nor apical aneurysm was associated with adverse outcomes. Incident CE stroke occurred in 41 patients (9%) and was independently associated with prior CE stroke and LV thrombus. Conclusion In CCM, CE stroke is primarily driven by LV thrombus formation. Apical aneurysm increases embolic risk mainly through thrombus mediation, while prior CE stroke identifies patients at increased risk for recurrence. These findings support targeted stroke prevention strategies focused on thrombus detection and anticoagulation.