Determinants and Prognostic Value of Atrial and Ventricular Ectopic Burden in Adults Without Structural Heart Disease

Abstract

Atrial and ventricular ectopy are frequently encountered during ambulatory monitoring in asymptomatic adults; however, their independent long-term prognostic significance in low-risk populations without structural heart disease remains a subject of ongoing clinical debate. To identify the distinct clinical and physiological determinants of atrial ectopic burden (AEB) and ventricular ectopic burden (VEB), and to evaluate their independent long-term associations with major adverse cardiovascular events (MACE) in a primary prevention cohort. We evaluated 931 asymptomatic individuals (mean age 52 ± 7 years; 13% female) without structural heart disease who completed a baseline 24-hour Holter recording. High AEB and VEB were defined using cohort-specific medians and/or the presence of ambulatory arrhythmic complexity. Complete longitudinal tracking for MACE (composite of acute coronary syndrome, cerebrovascular accident, new-onset heart failure or cardiovascular mortality) was available for 840 participants over a median follow-up of 8 years (IQR 5-11 years). To evaluate the robustness of the atrial findings, a prespecified sensitivity analysis was performed by excluding patients with baseline atrial fibrillation (AF). Over the follow-up period, the primary MACE endpoint occurred in 149 (18%) participants. In multivariable logistic regression models, high AEB was independently driven by older age (OR 1.09, 95% CI 1.06-1.12; p < 0.001), male sex (OR 1.60, 95% CI 1.02-2.52; p = 0.042), reduced eGFR (OR 0.98, 95% CI 0.97-0.99; p = 0.049), and low cardiorespiratory fitness (OR 1.38, 95% CI 1.01-1.92; p = 0.049). Conversely, high VEB was independently associated only with older age (OR 1.04, 95% CI 1.02-1.07; p < 0.001) and reduced eGFR (OR 0.98, 95% CI 0.97-0.99; p = 0.034). In fully adjusted multivariable Cox proportional hazards models, high VEB remained a robust independent predictor of MACE, conferring a three-fold increase in risk (HR 3.06, 95% CI 2.06-4.56; p < 0.001). In tertile-based analyses of pure ectopic burden, increasing VEB demonstrated a robust graded association with MACE after adjustment for age, sex, beta-blocker use and antiarrhythmic drug therapy (HR per tertile increase 2.02, 95% CI 1.60-2.53; p < 0.001), whereas AEB showed only a borderline association that did not reach statistical significance (HR per tertile increase 1.21, 95% CI 0.98-1.50; p = 0.076). In asymptomatic adults without structural heart disease, the clinical determinants and long-term prognostic trajectories of ectopy exhibit a profound chamber-specific divergence. Ventricular ectopic burden stands out as a powerful, independent marker of intrinsic electrical vulnerability and long-term cardiovascular risk. Meanwhile, atrial ectopy is highly sensitive to systemic physiological fitness and carries a weaker prognostic signal that attenuates completely upon multivariate clinical and medication adjustment.