Impact of Myocardial Fibrosis and Female Sex on Life-Threatening Arrhythmias and Sudden Cardiac Death in Mitral Valve Prolapse

BACKGROUND: Mitral valve prolapse (MVP) is a common cardiac condition that is generally benign, yet a subset of affected patients develop malignant ventricular arrhythmias and sudden cardiac death. Female sex and myocardial fibrosis detected by late gadolinium enhancement on cardiovascular magnetic resonance imaging have been proposed as risk factors though their independent contributions to arrhythmic risk remain uncertain. METHODS: We conducted a prospective cohort study of 550 consecutive patients with MVP referred for cardiovascular magnetic resonance at a tertiary academic center between May 2008 and December 2021. Patients with potential confounders, including coronary artery disease, cardiomyopathy, infiltrative disease, or prior cardiac surgery, were excluded. The primary end point was a composite arrhythmic outcome comprising sudden cardiac death, aborted sudden cardiac arrest, and symptomatic sustained or inducible ventricular tachycardia or ventricular fibrillation leading to implantable cardioverter defibrillator placement or ventricular ablation at an MVP-related scar site. RESULTS: Among the 550 patients (median age, 62 [interquartile range, 52–71] years; 50% women), LGE was present in 210 (38%). Over a median follow-up of 4.4 years (interquartile range, 2.8–7.1; 2700 patient-years), 48 patients (8.7%) reached the primary end point. On univariable analysis, both female sex (hazard ratio, 3.33 [95% CI, 1.72–6.44]; P <0.001) and LGE presence (hazard ratio, 3.17 [95% CI, 1.74–5.77]; P <0.001) were significantly associated with arrhythmic events, and both remained independently associated on multivariable analysis. Women with LGE represented the highest-risk subgroup, with a 5-year event-free survival of 76.5%, compared with 98.5% in men without LGE ( P <0.001). CONCLUSIONS: In a large prospective cardiovascular magnetic resonance cohort of patients with MVP, female sex and myocardial fibrosis were each independently associated with life-threatening arrhythmic events. Their combination identified a subgroup at particularly elevated risk, highlighting the importance of integrating sex-specific factors and myocardial tissue characterization into MVP risk stratification strategies.