Background Mitral valve prolapse (MVP) is one of the most common forms of cardiac valve disease and affects 2% to 3% of the population. Previous imaging reports have indicated that myocardial fibrosis is common in MVP and described its association with sudden cardiac death. These data combined with evidence for postrepair ventricular dysfunction in surgical patients with MVP support a link between fibrosis and MVP. Methods and Results We performed histopathologic analysis of left ventricular (LV) biopsies from peripapillary regions, inferobasal LV wall and apex on surgical patients with MVP, as well as in a mouse model of human MVP ( Dzip1 S14R /+ ). Tension‐dependent molecular pathways were subsequently assessed using both computational modeling and cyclical stretch of primary human cardiac fibroblasts in vitro. Histopathology of LV biopsies revealed regionalized fibrosis in the peripapillary myocardium that correlated with increased macrophages and myofibroblasts. The MVP mouse model exhibited similar regional increases in collagen deposition that progress over time. As observed in the patient biopsies, increased macrophages and myofibroblasts were observed in fibrotic areas within the murine heart. Computational modeling revealed tension‐dependent profibrotic cellular and molecular responses consistent with fibrosis locations related to valve‐induced stress. These simulations also identified mechanosensing primary cilia as involved in profibrotic pathways, which was validated in vitro and in human biopsies. Finally, in vitro stretching of primary human cardiac fibroblasts showed that stretch directly activates profibrotic pathways and increases extracellular matrix protein production. Conclusions The presence of prominent regional LV fibrosis in patients and mice with MVP supports a relationship between MVP and progressive damaging effects on LV structure before overt alterations in cardiac function. The regionalized molecular and cellular changes suggest a reactive response of the papillary and inferobasal myocardium to increased chordal tension from a prolapsing valve. These studies raise the question whether surgical intervention on patients with MVP should occur earlier than indicated by current guidelines to prevent advanced LV fibrosis and potentially reduce residual risk of LV dysfunction and sudden cardiac death.

OBJECTIVES Mitral valve (MV) annuloplasty ring dehiscence with subsequent recurrent mitral regurgitation represents an unusual but challenging clinical problem. Incidence, localization and outcomes for this complication have not been well defined. METHODS From 1996 to 2016, a total of 3478 patients underwent isolated MV repair with ring annuloplasty at the Leipzig Heart Centre. Of these patients, 57 (1.6%) underwent reoperation due to annuloplasty ring dehiscence. Echocardiographic data, operative and early postoperative characteristics as well as short- and long-term survival rates after MV reoperation were analysed. RESULTS Occurrences of ring dehiscence were acute (<30 days), early (≤1 year) and late (>1 year) in 44%, 33% and 23% of patients, respectively. Localization of annuloplasty ring dehiscence was found most frequently in the P3 segment (68%), followed by the P2 (51%) and the P1 segments (47%). The 30-day mortality rate and 1- and 5-year survival rates after MV reoperation were 2%, 89% and 74%, respectively. During reoperation, MV replacement was performed in 38 (67%) and MV re-repair in 19 (33%) patients. CONCLUSIONS Annuloplasty ring dehiscence is clinically less common, localized more frequently on the posterior annulus and occurs mostly acutely or early after MV repair. MV reoperation can be performed safely in such patients.

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OBJECTIVES The goal of this study was to quantify the mitral valve (MV) annulus, the MV shape and the anatomical MV orifice area throughout the cardiac cycle using 4-dimensional MV analysis software in patients with primary mitral regurgitation (PMR) and secondary mitral regurgitation (SMR) in comparison to a healthy control group. METHODS Three-dimensional transoesophageal echocardiograms of the MV were acquired for 29 patients with PMR, for 28 patients with SMR and for 18 healthy control subjects. The MV was quantified with regards to anterior-posterior and lateromedial diameter, annular area and circumference, intertrigonal (IT) distance, annular sphericity index, annular height to commissural width ration, and anatomical MV orifice area throughout the cardiac cycle using 3-dimensional transoesophageal echocardiography-based 4-dimensional MV advanced analysis software. RESULTS Normal annulus dynamics display a systolic enlargement followed by an early-diastolic plateau phase and a late-diastolic contraction. The IT distance showed a linear association with the anterior-posterior diameter (= 1.11 × IT distance) and lateromedial diameter (= 1.44 × IT distance) in the control subjects. Mitral regurgitation is associated with a less dynamic, planar and dilated annulus with small variations between PMR and SMR. The IT distance was less affected by mitral regurgitation compared to the control subjects. CONCLUSIONS The novel 4-dimensional MV analysis allows new insights into the dynamic MV geometry in patients with PMR and SMR compared to the control subjects. The IT distance may be used to predict annuloplasty ring sizing.

Background Four-dimensional cardiovascular magnetic resonance (CMR) flow assessment (4D flow) allows to derive volumetric quantitative parameters in mitral regurgitation (MR) using retrospective valve tracking. However, prior studies have been conducted in functional MR or in patients with congenital heart disease, thus, data regarding the usefulness of 4D flow CMR in case of a valve pathology like mitral valve prolapse (MVP) are scarce. This study aimed to evaluate the clinical utility of cine-guided valve segmentation of 4D flow CMR in assessment of MR in MVP when compared to standardized routine CMR and transthoracic echocardiography (TTE). Methods Six healthy subjects and 54 patients (55 ± 16 years; 47 men) with MVP were studied. TTE severity grading used a multiparametric approach resulting in mild/mild-moderate (n = 12), moderate-severe (n = 12), and severe MR (n = 30). Regurgitant volume (RVol) and regurgitant fraction (RF) were also derived using standard volumetric CMR and 4D flow CMR datasets with direct measurement of regurgitant flow (4DFdirect) and indirect calculation using the formula: mitral valve forward flow - left ventricular outflow tract stroke volume (4DFindirect). Results There was moderate to strong correlation between methods (r = 0.59–0.84, p < 0.001), but TTE proximal isovelocity surface area (PISA) method showed higher RVol as compared with CMR techniques (PISA vs. CMR, mean difference of 15.8 ml [95% CI 9.9–21.6]; PISA vs. 4DFindirect, 17.2 ml [8.4–25.9]; PISA vs. 4DFdirect, 27.9 ml [19.1–36.8]; p < 0.001). Only indirect CMR methods (CMR vs. 4DFindirect) showed moderate to substantial agreement (Lin’s coefficient 0.92–0.97) without significant bias (mean bias 1.05 ± 26 ml [− 50 to 52], p = 0.757). Intra- and inter-observer reliability were good to excellent for all methods (ICC 0.87–0.99), but with numerically lower coefficient of variation for indirect CMR methods (2.5 to 12%). Conclusions In the assessment of patients with MR and MVP, cine-guided valve segmentation 4D flow CMR is feasible and comparable to standard CMR, but with lower RVol when TTE is used as reference. 4DFindirect quantification has higher intra- and inter-technique agreement than 4DFdirect quantification and might be used as an adjunctive technique for cross-checking MR quantification in MVP.