Determinants and prognostic value of atrial and ventricular ectopic burden in adults without structural heart disease

Abstract

Abstract Aims 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. Purpose 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. Methods and results We evaluated 931 asymptomatic individuals (mean age 52 ± 7 years; 13% female) without structural heart disease who completed a baseline 24-h 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. 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 estimated glomerular filtration rate (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 0.977–0.99; 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). Conclusion 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.