Interstitial Fibrosis and Arrhythmic Mitral Valve Prolapse: Unravelling Sex-Based Differences

Abstract

ABSTRACTBackgroundInterstitial fibrosis as quantified by cardiac magnetic resonance (CMR) has been demonstrated in arrhythmic mitral valve prolapse (MVP), a condition with known female predominance. However, prior studies included only MVP cases with significant mitral regurgitation (MR) or mitral annular disjunction (MAD). We sought to evaluate the association between interstitial fibrosis and complex ventricular ectopy (ComVE) in MVPs unselected for MAD or severe MR, and to investigate the contribution of sex to this association.MethodsWe performed contrast CMR in consecutive individuals with MVP between 2020 and 2022. Extracellular volume fraction (ECV%), a surrogate marker for interstitial fibrosis, was quantified using T1mapping. Replacement fibrosis was assessed using late gadolinium enhancement (LGE). ComVE, defined as frequent premature ventricular contractions and/or non-sustained/sustained ventricular tachycardia (VT), was detected using ambulatory ECG monitoring.ResultsWe identified 59 MVP cases without severe MR (49% women, 80% with mild or less MR) and available ECV% measurement. Among these, 23 (39%) had ComVE, including a case of aborted ventricular fibrillation (VF) and one with sudden arrhythmic death, both females. Global ECV% was significantly greater in ComVE versus non-ComVE (31%[27-33] vs 27%[23-30], p=0.002). In MVP-ComVE, higher segmental ECV% was not limited to the inferolateral/inferior LV wall, but was also demonstrated in atypical segments including the anterior/anterolateral wall (p<0.05). The association between ComVE and ECV% was driven by female sex (32%[30-33] vs 28%[26-30], p=0.003 in females; 31%[25-33] vs 26%[23-30], p=0.22 in males). ECV% remained independently associated with an increased risk of ComVE, including VT/VF, after adjustment for cardiovascular risk factors, MAD, and LGE (p<0.01).ConclusionIn MVP without significant MR, interstitial fibrosis by CMR is associated with an increased risk of ComVE, suggesting a primary myopathic process. The stronger association between interstitial fibrosis and ComVE in females may explain why severe arrhythmic complications are more prevalent among women.Abstract FigureGRAPHICAL ABSTRACT:Expansion of Interstitial Myocardial Fibrosis in Mitral Valve Prolapse with Complex Ventricular Ectopy. Illustrative MVP case with ComVE and greater interstitial fibrosis as demonstrated by T1mapping on CMR (Top). The violin plot shows significantly greater ECV% in MVPs with ComVE compared to non-ComVE (Top). The association between greater interstitial fibrosis (i.e. ECV%) and ComVE was stronger in women than men (Bottom). MR = mitral regurgitation