Presentation and Outcome of Arrhythmic Mitral Valve Prolapse

BACKGROUND Mitral valve prolapse (MVP) is often considered benign but recent suggestion of an arrhythmic MVP (AMVP) form remains incompletely defined and uncertain. OBJECTIVES This study determined ventricular arrhythmia prevalence, severity, phenotypical context, and independent impact on outcome in patients with MVP. METHODS A cohort of 595 (age 65 ± 16 years; 278 women) consecutive patients with MVP and comprehensive clinical, arrhythmia (24-h Holter monitoring) and Doppler-echocardiographic characterization, was identified. Long-term outcomes were analyzed. RESULTS Ventricular arrhythmia was frequent (43% with at least ventricular ectopy ≥5%), most often moderate (ventricular tachycardia VT; 120 to 179 beats/min) in 27%, and rarely severe (VT ≥180 beats/min) in 9%. Presence of ventricular arrhythmia was associated with male sex, bileaflet prolapse, marked leaflet redundancy, mitral annulus disjunction (MAD), a larger left atrium and left ventricular end-systolic diameter, and T-wave inversion/ST-segment depression (all p ≤ 0.001). Severe ventricular arrhythmia was independently associated with presence of MAD, leaflet redundancy, and T-wave inversion/ST-segment depression (all p < 0.0001) but not with mitral regurgitation severity or ejection fraction. Overall mortality after arrhythmia diagnosis (8 years; 13 ± 2%) was strongly associated with arrhythmia severity (8 years; 10 ± 2% for no/trivial, 15 ± 3% for mild and/or moderate, and 24 ± 7% for severe arrhythmia; p = 0.02). Excess mortality was substantial for severe arrhythmia (univariate hazard ratio HR: 2.70; 95% confidence interval CI: 1.27 to 5.77; p = 0.01 vs. no/trivial arrhythmia), even after it was comprehensively adjusted, including for MVP characteristics (adjusted HR: 2.94; 95% CI: 1.36 to 6.36; p = 0.006) and by time-dependent analysis (adjusted HR: 3.25; 95% CI: 1.56 to 6.78; p = 0.002). Severe arrhythmia was also associated with higher rates of mortality, defibrillator implantation, VT ablation (adjusted HR: 4.68; 95% CI: 2.45 to 8.92; p < 0.0001), particularly under medical management (adjusted HR: 5.80; 95% CI: 2.75 to 12.23; p < 0.0001), and weakly post-mitral surgery (adjusted HR: 3.69; 95% CI: 0.93 to 14.74; p = 0.06). CONCLUSIONS In this large cohort of patients with MVP, ventricular arrhythmia by Holter monitoring was frequent but rarely severe. AMVP was independently associated with phenotype dominated by MAD, marked leaflet redundancy, and repolarization abnormalities. Long-term severe arrhythmia was independently associated with notable excess mortality and reduced event-free survival, particularly under medical management. Therefore, AMVP is a clinical entity strongly associated with outcome and warrants careful risk assessment and well-designed clinical trials.