Predictors of ischemic stroke in Chagas disease: Insights into mechanisms beyond cardiomyopathy severity

Background: Chagas disease is a risk factor for ischemic stroke, which causes high mortality rates and significant disability. This study aims to determine the incidence and risk factors for ischemic strokes in a large cohort of Chagas cardiomyopathy patients, with a particular focus on the mechanisms involved in the pathophysiology of stroke in this condition. Methods: The study enrolled 517 patients with Chagas cardiomyopathy who were referred to our institution from March 2000 to December 2021. All patients underwent systematic cardiological and neurological assessments. The primary outcome was the occurrence of ischemic stroke during the follow-up period, classified based on the SSS-TOAST and CCS criteria. Natural cubic splines functions were applied to examine the potential nonlinear association between continuous variables and stroke risk. Results: The mean age of the cohort was 52 ± 13 years, and 299 (58 %) were men. During a mean follow-up period of 4.8 years (interquartile range-IQR 1.1 to 7.1 years), a total of 72 patients (14.8 %) had an ischemic stroke, being fatal in 10. The overall incidence rate of ischemic stroke was 3.0/100 patient-years (95 % confidence interval 2.4 to 3.8). The stroke subtypes were cardioembolic (n = 41), undetermined (n = 11), and other subtypes (n = 20). The predictors of stroke were age, left atrial volume, left ventricular ejection fraction (LVEF), LV thrombus and prior stroke with thrombus. There was a nonlinear relationship between stroke risk, LVEF, and left atrial volume. A bimodal distribution of stroke occurrences was observed according to the severity of LV dysfunction, with a threshold for LVEF of 45 %. The final model for stroke risk prediction showed good discrimination, with a C statistic of 0.775. Conclusions: In a contemporary cohort of Chagas disease patients with a broad spectrum of disease severity, stroke incidence remains high despite anticoagulation. Stroke risk shows a nonlinear association with ventricular dysfunction and left atrial size, highlighting a distinct bimodal pattern of stroke occurrence in Chagas disease.