Abstract 4141535: Annulo-Leaflet Mitral Ring – A Distinct Form of Valvar Endocardial Fibroelastosis

Introduction: Treatment of congenital mitral stenosis (MS) is a major challenge due to high recurrence rate necessitating reintervention. The annulo-leaflet mitral ring (ALMR) is a unique form of congenital MS, defined as fibrous ridge/membrane located above the mitral valve (MV) and/or adherent to leaflets’ atrial surface. The underlying mechanism of ALMR formation and recurrence is unknown. Objective: We sought to determine recurrence of ALMR following primary resection and to establish the cellular mechanism of ALMR formation. Methods: A retrospective single-center cohort study of patients undergoing primary resection of an ALMR between 01/2013 and 12/2023 was conducted. The primary outcome was ALMR recurrence. Mean diastolic MV gradient and type of MV disease were determined by echocardiography. In a subset of patients with available tissue, cellular analysis was performed for endocardial fibroelastosis (EFE). Results: In total, 50 patients (median age 20.5 (IQR 57) months), of which 78% had additional subvalvar MV anomalies, underwent primary ALMR resection, decreasing mean MV gradient from 9.7±4.96mmHg to 4.8±3.46mmHg (p<0.001). At discharge, 2 patients (4%) had residual ALMR, 19 (38%) MS, and 21 (42%) MV regurgitation (MR). At a median follow-up of 45 (IQR 40) months, 21 patients (42%) had MS and 14 (28%) MR, 9 (18%) underwent MV replacement, 2 (4%) experienced late deaths, and 8 (16%) were lost to follow-up. ALMR recurred in 12 patients (32%), all with additional subvalvar anomalies, and 11 (29%) underwent re-resection at a median interval of 21 (IQR 24) months. Cellular mechanism is displayed in Figure 1. Conclusion: Our findings show that ALMR occurs as part of a broader MV-disease complex, resulting in a high recurrence rate. We reveal for the first time that ALMR tissue originates from the endocardium through EndMT and is, hence, a distinct form of EFE. Flow disturbances due to an abnormal subvalvar MV apparatus are the likely driving force behind EFE in ALMR recurrence, which is in support of our previous findings from other complex congenital heart defects. Pharmacologically targeting the EndMT pathway might reduce disease burden for these patients and thus, could be a novel therapeutical approach.