Mitral valve prolapse and the long-term risk of ventricular arrhythmias, cardiac arrest, and im-plantable cardioverter-defibrillator implantation

Background A subset of patients with mitral valve prolapse appear to have an increased risk of ventricular arrhythmias and sudden cardiac death. However, current knowledge is primarily derived from selected or event-driven cohorts, warranting broader insight into the magnitude of the risk in unselected populations. Purpose To investigate the long-term risk of ventricular arrhythmias, cardiac arrest and implantable cardioverter-defibrillator (ICD) implantation in patients with mitral valve prolapse compared with the general population. Methods Using Danish nationwide registries, all adult patients with a first-time diagnosis of mitral valve prolapse between 2000 and 2022 were matched 1:4 by sex, age, year of diagnosis and relevant comorbidities with controls from the background population. Exclusion criteria prior to matching were history of one of the arrhythmic endpoints, ischemic heart disease, heart failure, prior heart surgery or ICD implantation. The cumulative 10-year incidence of a primary composite endpoint (ventricular tachycardia/fibrillation/flutter, cardiac arrest or ICD implantation) was estimated with death as competing risk and mitral valve surgery as censoring. Mortality was estimated using the Kaplan-Meier method. Outcome rates were compared using a univariate Cox regression model conditional on the matching. Results We identified 4,395 patients with mitral valve prolapse and 17,580 matched controls from the background population (median age: 64.4 years; 57.6% men). Comorbidities were overall similar between patients and controls, although hypertension (24.6% vs. 20.6%) and atraumatic bleeding (11.4% vs. 9.1%) were more frequent among patients (p<0.001). Median follow-up time was 7.61 years (95% CI 3.58-10.0) for the combined cohort. Ventricular arrhythmias occurred in 0.84% patients vs. 0.33% controls, cardiac arrest in 0.86% vs. 0.59%, and ICD implantation in 0.43% vs. 0.14% (all p<0.05). The 10-year cumulative incidence of the primary composite outcome was 2.9% in patients compared to 1.2% in controls (p<0.001), Figure 1. In Cox regression, this corresponded to a significantly higher hazard of the primary composite outcome in patients compared to controls (HR 2.66 [95% CI 2.00–3.63], p<0.001). Cumulative 10-year mortality was 25.4% in patients compared to 23.3% in controls (p=0.003), corresponding to a significantly higher hazard in patients compared to controls (HR 1.19 [95% CI 1.10–1.30], p<0.001). Conclusion(s) Mitral valve prolapse was associated with a significantly higher long-term risk of severe arrhythmic outcomes and mortality compared with a matched background population. These findings emphasize the need for improved risk stratification to guide clinical management in patients with mitral valve prolapse.