Electro-mechanical dissociation in Chagas cardiomyopathy: comparative analysis of arrhythmic burden beyond LVEF

Background Chronic Chagas cardiomyopathy (CCC) is characterized by extensive myocardial fibrosis, neuroautonomic dysfunction, and a high incidence of sudden cardiac death (SCD), even in patients with preserved left ventricular systolic function. Current guidelines for implantable cardioverter-defibrillator (ICD) implantation rely predominantly on left ventricular ejection fraction (LVEF) thresholds derived from ischemic cardiomyopathy trials, yet no validated risk stratification models address the unique arrhythmogenic substrate of CCC. This study aimed to compare arrhythmic burden, myocardial deformation, and autonomic dysfunction between patients with CCC and those with ischemic cardiomyopathy (IC), matched for systolic function and neurohormonal activation. Methods We performed a cross-sectional baseline analysis of 146 heart failure patients enrolled in the Empa-Chagas prospective cohort at a tertiary cardiovascular center in Colombia (75 CCC, 71 IC), matched for age, LVEF, and NT-proBNP levels. All participants underwent transthoracic echocardiography with speckle-tracking strain analysis and 24-hour Holter monitoring. Non-sustained ventricular tachycardia (NSVT) was defined as ≥3 consecutive ventricular beats at >100 bpm lasting <30 seconds, and high ventricular ectopy burden as premature ventricular complexes (PVCs) comprising ≥10% of total beats. Multivariable generalized linear models adjusted for age, sex, LVEF, and NT-proBNP were used to compare arrhythmic parameters between groups. Results Despite comparable systolic function, CCC patients exhibited a significantly higher arrhythmic burden, with greater prevalence of high ventricular ectopy (45.3% vs. 5.6%, p<0.001) and NSVT (30.7% vs. 7.0%; adjusted RR 4.37, 95% CI 1.67–11.39, p=0.002). Critically, NSVT prevalence in CCC was similar across LVEF strata (33.3% in LVEF ≥40% vs. 29.2% in LVEF <40%, p=0.707). Regional strain analysis revealed characteristic inferolateral and inferior wall involvement in CCC. Conventional heart failure severity markers, including worse global and regional strain, were associated with NSVT in IC but not in CCC, where atrial fibrillation (p=0.002) and ventricular aneurysms (p=0.033) were the primary associated variables. Conclusions In CCC, arrhythmic vulnerability is decoupled from global systolic function and conventional markers of heart failure severity. LVEF-based risk stratification systematically underestimates sudden death risk in this population. Substrate and rhythm-based markers, including ventricular aneurysms and ectopy burden, may improve identification of high-risk CCC patients and support the development of etiology-specific criteria for ICD indication.