Mitral annular disjunction and its arrhythmic risk in mitral valve prolapse: a metanalysis

Background Mitral annular disjunction (MAD) is a condition characterized by the abnormal attachment of the posterior mitral leaflet directly to the atrial wall. This condition is particularly prevalent in patients with mitral valve prolapse (MVP). The growing interest in MAD arises from various studies that have indicated its potential arrhythmic role. However, the findings are still controversial, and further research is needed to clarify its implications. Objective To better assess the arrhythmic risk linked to the presence of MAD in patients with MVP. Method We conducted a systematic search of the Medline, Cochrane, and Scopus electronic databases for studies published from their inception through December 2024. Our focus was on studies comparing arrhythmic MAD with non-arrhythmic MAD. Two investigators, L.O. and M.A.L., independently performed the searches using the following terms: mitral annular disjunction, mitral valve disjunction, ventricular arrhythmias, mitral valve prolapse, and sudden cardiac death. The prognostic performance of MAD in predicting major arrhythmias in the MVP population was summarized using pooled estimates for sensitivity, specificity, diagnostic odds ratio (DOR), negative predictive value (NPV), and positive predictive value (PPV). Confidence intervals were calculated using the DerSimonian and Laird method (1986, ref 1). Due to varying thresholds for identifying MAD, moderate heterogeneity was expected, assessed with I-squared and Kendall's Tau. A random-effects model was used when heterogeneity was not extremely low. The summary receiver operating characteristic (sROC) curve and area under the curve (AUC) were computed using a non-parametric summary ROC method, as described by Martinez-Camblor. Statistical analysis was performed with R version 4.4.0. Results After reviewing 66 articles, we identified a total of 7 studies enrolling 1977 patients with MVP. Of these 1171 MVP with MAD and 806 without MAD. MAD was defined as abnormal separation between the mitral valve junction and LV wall with a length of at least 1 mm (5 studies) or 2 mm (2 studies). MAD was assessed with echocardiography (4 studies) or cardiac magnetic resonance (CMR) (3 studies). In patients with MVP, MAD was associated with an increased arrhythmic risk with OR of 2.604 (95% CI: 2.012; 3.371) (Figure, upper panel). MAD resulted as an arrhythmic risk factor in patients with MVP with an AUC of 0.603 (Figure, lower panel). Conclusions While MVP is generally considered a benign condition, a subset of patients may face an elevated risk of life-threatening arrhythmias. Our findings suggest that MAD is a significant risk factor for arrhythmias in patients with MVP, reinforcing the need for careful evaluation and risk stratification in this population. Future studies should focus on refining MAD detection methods and establishing standardized diagnostic thresholds to improve risk prediction and clinical management.