Arrhythmic risk in mitral valve prolapse with mitral annular disjunction: meta-analysis of longitudinal studies

Mitral valve prolapse (MVP) is frequently associated with mitral annular disjunction (MAD). Although numerous studies and emerging consensus suggest an arrhythmogenic role for MAD, there is a lack of large-scale meta-analyses of longitudinal studies to definitively confirm this association. We aim to evaluate the longitudinal arrhythmic risk in patients with MVP and MAD. We systematically searched PubMed, Cochrane Library, and Scopus for longitudinal studies assessing arrhythmic risk in MVP patients with MAD, from inception to May 2025. Diagnostic performance measures (sensitivity, specificity, diagnostic odds ratio, positive/negative predictive values) were pooled. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using a DerSimonian and Laird random-effects model. Heterogeneity was assessed via I² and Kendall's tau. The summary receiver operating characteristic (sROC) curve and area under the curve (AUC) were estimated using Martínez-Camblor's method. Six studies, including 1880 MVP patients, 751 with MAD, and 1129 without, were analyzed. There was no unique method to diagnose MAD. The pooled prevalence of MAD was 36% (95% CI 22-53%). MAD was associated with increased arrhythmic risk (OR: 2.60; 95% CI: 1.99-3.38, I²: 14.7%, p < 0.0001). Sensitivity and specificity were 0.512 (95% CI: 0.245-0.778) and 0.667 (95% CI: 0.506-0.828), respectively. The AUC was 0.561. MAD is linked to an increased risk of arrhythmias in MVP. However, its predictive accuracy remains limited. This is due to the possible influence of additional prognostic factors and, importantly, to the absence of standardized protocols for MAD measurement, including imaging techniques and anatomical reference points.