Frequent premature ventricular complexes and risk of atrial fibrillation, heart failure, stroke and mortality: a meta-analysis.

Background/aim: Frequent premature ventricular complexes (PVCs) have historically been regarded as benign in structurally normal hearts, yet emerging evidence suggests substantial cardiovascular risk. This meta-analysis aimed to quantify associations between frequent PVCs and incident atrial fibrillation, heart failure, stroke and all-cause mortality in adults without established cardiovascular disease.

Methods: PubMed/MEDLINE, Embase, CENTRAL, Web of Science and Scopus were searched through February 2025. Databases were searched from inception to February 2025. Eligible studies employed standardised PVC assessment methods with a minimum 12-month follow-up reporting adjusted effect estimates. Data were independently extracted and quality was assessed (Risk of Bias in Non-randomized Studies of Interventions) by two reviewers. Random-effects meta-analyses yielded pooled HRs with 95% CIs and prediction intervals (PI). Study-level meta-regression was used to evaluate dose-response relationships, and heterogeneity sources were explored via further meta-regression.

Outcomes: 20 articles (17 studies; 26 783 590 participants) were analysed. Frequent PVCs were significantly associated with increased risks of atrial fibrillation (HR 1.69, 95% CI 1.39 to 2.05; PI 0.91-3.12), heart failure (HR 1.73, 95% CI 1.50 to 2.00; PI 1.18-2.54), stroke (HR 1.28, 95% CI 1.10 to 1.50; PI 0.90-1.82) and all-cause mortality (HR 1.31, 95% CI 1.10 to 1.56; PI 0.79-2.18). Heterogeneity was substantially reduced in sensitivity analyses restricted to Holter-quantified PVCs. Meta-regression identified a 5.4% increased atrial fibrillation risk per 1% increment in PVC burden.

Conclusion: Frequent PVCs confer significantly increased cardiovascular risks in populations largely without overt structural heart disease, though baseline cardiac assessment varied across studies. Patients with frequent PVCs (≥500/day) may benefit from periodic echocardiography and rhythm monitoring to detect early structural or arrhythmic progression. Randomised trials are needed to determine if PVC burden-guided interventions can reduce cardiovascular risk.

Prospero registration number: CRD420251006111.