From benign to prognostic: ectopy burden predicts long-term cardiovascular events

Background Atrial and ventricular ectopy are frequent in apparently healthy adults and increase with age, yet their prognostic relevance for cardiovascular disease remains unclear. Identifying early electrophysiologic markers may refine preventive risk stratification. Purpose To assess whether a composite measure of atrial and ventricular ectopic burden, including AF, PAT and NSVT, independently predicts cardiovascular events in structurally normal adults. Methods We analyzed 931 adults (mean age 52 ± 7 years; 12% female) without structural heart disease, LV dysfunction or major comorbidities who underwent Holter monitoring and exercise testing (2010–2022). High atrial ectopic burden (AEB) was defined as ectopic burden above the median and/or AF/PAT. High ventricular ectopic burden (VEB) was defined as ectopic burden above the median and/or NSVT. The primary endpoint was the first cardiovascular event (ACS, CVA, HF or cardiovascular-related death). Cox proportional hazards models were adjusted for age and sex. Results Survival data were available for 840 participants. Over a median follow-up of 4 years, 150 first cardiovascular events occurred (18%; 70 ischemic events, 57 strokes, 29 heart failure hospitalizations and 1 cardiovascular death). Participants with high atrial ectopic burden (AEB) experienced significantly more events than those with low AEB (21% vs 14%, HR 1.53, 95% CI 1.05–2.24, p = 0.01). The impact of ventricular ectopy was even more pronounced, high VEB was associated with a doubling of risk (29% vs 12%, HR 2.82, 95% CI 1.91–4.18, p < 0.001). Notably, the divergence in Kaplan–Meier survival curves emerged early and widened progressively, suggesting an accumulating risk associated with ectopic burden. Conclusion These findings highlight ectopy burden as a widely available, inexpensive biomarker derived from routine Holter monitoring. Beyond traditional risk factors, electrophysiologic aging may represent a missing component of cardiovascular risk prediction. Prospective validation and integration into preventive algorithms may allow earlier identification of individuals who appear healthy yet harbor elevated cardiovascular risk.