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.

Stroke in Chagas disease: from pathophysiology to clinical practice.

Despite substantial progress toward its control, Chagas disease continues to be a major public health problem in Latin America and has become a global health concern. The disease affects approximately 6 million people, of whom 20-40% will develop cardiomyopathy over the years after the initial Trypanosoma cruzi infection. Chagas cardiomyopathy is the most serious and frequent manifestation of Chagas disease. Clinical manifestations vary widely according to the severity of myocardial dysfunction, ranging from asymptomatic to severe forms, including dilated cardiomyopathy with heart failure, arrhythmias, thromboembolism events, and sudden death. Chagas disease is a risk factor for stroke regardless of the severity of cardiomyopathy, which is a leading cause of chronic disability. Classically, stroke etiology in patients with Chagas disease is thought to be cardioembolic and related to apical aneurysm, mural thrombus, and atrial arrhythmias. Although most strokes are thromboembolic, other etiologies have been observed. Small vessel disease, atherosclerosis, and cryptogenic diseases have been reported in patients with Chagas disease and stroke. The potential mechanisms involved in non-embolic strokes include the presence of associated risk factors, pro-inflammatory and prothrombotic disease states, and endothelial dysfunction. However, the contribution of each mechanism to stroke in Chagas disease remains unclear. The review aims to provide an overview of stroke in Chagas disease, highlighting the main pathophysiological mechanisms, clinical presentation, approaches for prevention, and unanswered questions regarding treatment strategies.

Stroke in Chagas disease: from pathophysiology to clinical practice

ABSTRACT Despite substantial progress toward its control, Chagas disease continues to be a major public health problem in Latin America and has become a global health concern. The disease affects approximately 6 million people, of whom 20-40% will develop cardiomyopathy over the years after the initial Trypanosoma cruzi infection. Chagas cardiomyopathy is the most serious and frequent manifestation of Chagas disease. Clinical manifestations vary widely according to the severity of myocardial dysfunction, ranging from asymptomatic to severe forms, including dilated cardiomyopathy with heart failure, arrhythmias, thromboembolism events, and sudden death. Chagas disease is a risk factor for stroke regardless of the severity of cardiomyopathy, which is a leading cause of chronic disability. Classically, stroke etiology in patients with Chagas disease is thought to be cardioembolic and related to apical aneurysm, mural thrombus, and atrial arrhythmias. Although most strokes are thromboembolic, other etiologies have been observed. Small vessel disease, atherosclerosis, and cryptogenic diseases have been reported in patients with Chagas disease and stroke. The potential mechanisms involved in non-embolic strokes include the presence of associated risk factors, pro-inflammatory and prothrombotic disease states, and endothelial dysfunction. However, the contribution of each mechanism to stroke in Chagas disease remains unclear. The review aims to provide an overview of stroke in Chagas disease, highlighting the main pathophysiological mechanisms, clinical presentation, approaches for prevention, and unanswered questions regarding treatment strategies.