Lobke L Pype, Oksana Marchenko, Sven L Van Laer, Bernard P Paelinck, Hanne M Boen, Nicole Sturkenboom, Pier Giorgio Masci, Rachel M A Ter Bekke, Julia Grapsa, Paul G A Volders, Emeline M Van Craenenbroeck, Caroline M Van De Heyning
LV remodeling in MVP is a multifactorial process, where, especially in patients with Barlow disease, the associated mitral annular dilatation and larger prolapse volume drive LV dilatation beyond MR severity. In addition, a burden of ≥3% ventricular ectopy is strongly correlated with LV dilatation and dysfunction. Finally, a monogenic cardiomyopathy substrate appears unlikely.
BACKGROUND: Left ventricular (LV) remodeling in mitral valve prolapse (MVP) may occur disproportionally to mitral regurgitation (MR) severity, especially in patients with Barlow disease. This study hypothesized an underlying MVP cardiomyopathy, potentially driven by ventricular arrhythmias or a genetic substrate. We investigated the determinants of LV remodeling in patients with MVP beyond MR volume load.
METHODS: Prospective inclusion of patients with nonsyndromic MVP at 3 centers. Patients were scheduled for cardiac magnetic resonance scans, 24-hour Holter monitoring, and the presence of an underlying cardiomyopathy-associated genetic variant was assessed. Disproportionate LV remodeling was defined as LV end-diastolic volume above the age- and sex-specific upper limit of normal after correction for the total MR volume load, using the following formula: (LV end-diastolic volume-MR volume)/body surface area-LVEDViULN >0.
RESULTS: A total of 103 patients with MVP were included (58% males, age 52±17 years). Disproportionate LV remodeling was present in 37% and was more frequent in Barlow disease compared with nonclassic MVP (P=0.067). After correction for age, sex, and MR volume load, Barlow disease phenotypic features like mitral annular dilatation are independently associated with LV dilatation (P<0.001 at multivariable regression analysis for left ventricular end-systolic volume index, R2=0.518). The total volume load (MR volume+prolapse volume) had a stronger correlation with LV remodeling than MR volume alone. In addition, ventricular arrhythmia-particularly ≥3% premature ventricular contractions-was independently associated with increased left ventricular end-systolic volume index even after correction for other classical risk factors (P=0.024, R2=0.518). None of the patients carried a likely pathogenic or pathogenic variant in cardiomyopathy-associated genes.
CONCLUSIONS: LV remodeling in MVP is a multifactorial process, where, especially in patients with Barlow disease, the associated mitral annular dilatation and larger prolapse volume drive LV dilatation beyond MR severity. In addition, a burden of ≥3% ventricular ectopy is strongly correlated with LV dilatation and dysfunction. Finally, a monogenic cardiomyopathy substrate appears unlikely.