Background The purpose of the study was to determine the association between vena contracta area (VCA) and secondary leaflet tethering among mitral valve prolapse (MVP) patients, and thus to further identify and characterize an MVP with pathological leaflet tethering (MVPt+) phenotype. Methods We prospectively evaluated 94 consecutive MVP patients with significant mitral regurgitation (MR) and 20 healthy controls. MVPt+ group was defined as tenting volume index (TVi) > 0.7 ml/m 2. The three-dimensional (3D) geometry of mitral valve apparatus and VCA was measured with dedicated quantification software. Results Of the 94 patients with MVP and significant MR, 31 patients showed a TVi > 0.7 ml/m 2 and entered the MVP with leaflet tethering (MVPt+) group. In stepwise multivariate analysis, only prolapse volume index and TVi was independently associated with 3D VCA. Apart from marked left ventricular and annular enlargement, MVPt+ group presented significantly higher frequency of leaflet flail, greater VCA, elevated plasma levels of NT-proBNP and sPAP. ROC curve revealed that occurrence of leaflet tethering is associated with a VCA ≥0.55 cm 2 in MVP patients. Conclusions Secondary leaflet tethering is a significant mechanism behind severe degenerative mitral regurgitation, resulting an MVPt+ phenotype featuring more advanced morphological and hemodynamical characteristics .

Background Multiple studies illustrated that mitral valve (MV) leaflet presented variations, and there is little known about the posterior mitral leaflet (PML) anatomical variation affecting residual MR in interventional mitral valve edge-to-edge repair (TEER) with the ValveClamp system in patients with degenerative mitral regurgitation (DMR) using three-dimensional transesophageal echocardiography (3D TEE). Method Fifty-five DMR patients treated with TEER were included and performed 3D TEE pre- and post-procedure immediately. 3D TEE images were proceeded to characterize the posterior mitral leaflet anatomy and investigate the relationship between variations and residual mitral regurgitation (MR). Results Variations in PML were found in 16 patients (32%) of this series, including 3 cases (6%) of one scallop, 8 cases (16%) of two scallops, and 5 cases (10%) of four scallops. Residual MR ≥ 2+ were found in 3 patients with variant PML and 8 patients with classical PML post procedures, while other patients were all < 2+. The Chi-square test results showed no correlation between residual MR and PML variants (18.8% vs. 23.5, ᵪ 2 = 0, p = 0.988). Of the 5 patients with 4 scallops, 3 had poor clinical outcomes. Two patients were converted to surgical mitral valve repair and one died 1 month after implantation. Conclusions 3D TEE provides a novel and non-invasive method to characterize and classify PML variations. Variations in PML are relatively common and not associated with residual MR 2+.

Gene mutations have been implicated in DCM. However, due to the difficulty of clinical genetic diagnosis, additional causal genes potentially related to DCM remain to be discovered.We screened for gene mutations in more than 400 cases from families with hereditary cardiovascular disease using whole-exome sequencing and then validated the biological functions of CHMP4C mutations in zebrafish models. To further assess the mechanism of CHMP4C mutations, we determined the potential signaling pathway in a cell line.We identified via whole-exome sequencing CHMP4C variants that segregated with DCM in four families among a total of 411 families. We further validated the function of CHMP4C in heart function in zebrafish models and found that overexpression of CHMP4C variants resulted in cardiac malformation, pericardial edema and an increased heart rate, consistent with CHMP4C mutation-associated findings in DCM patients. Furthermore, mutations in CHMP4C impaired autophagy and activated apoptosis in HEK293T cells, suggesting that the molecular mechanism of CHMP4C is involved in heart development.CHMP4C is a novel candidate gene causing DCM and may play a critical role in cardiac development by regulating autophagy.