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Background: In patients with myocardial infarction (MI), leaflet tethering by displaced papillary muscles induces mitral regurgitation (MR), which doubles mortality. Mitral valves (MVs) are larger in such patients but fibrosis sets in counterproductively. The investigators previously reported that experimental tethering alone increases mitral valve area in association with endothelial-to-mesenchymal transition., Objectives: The aim of this study was to explore the clinically relevant situation of tethering and MI, testing the hypothesis that ischemic milieu modifies mitral valve adaptation., Methods: Twenty-three adult sheep were examined. Under cardiopulmonary bypass, the papillary muscle tips in 6 sheep were retracted apically to replicate tethering, short of producing MR (tethered alone). Papillary muscle retraction was combined with apical MI created by coronary ligation in another 6 sheep (tethered plus MI), and left ventricular remodeling was limited by external constraint in 5 additional sheep (left ventricular constraint). Six sham-operated sheep were control subjects. Diastolic mitral valve surface area was quantified by 3-dimensional echocardiography at baseline and after 58 ± 5 days, followed by histopathology and flow cytometry of excised leaflets., Results: Tethered plus MI leaflets were markedly thicker than tethered-alone valves and sham control subjects. Leaflet area also increased significantly. Endothelial-to-mesenchymal transition, detected as α-smooth muscle actin-positive endothelial cells, significantly exceeded that in tethered-alone and control valves. Transforming growth factor-β, matrix metalloproteinase expression, and cellular proliferation were markedly increased. Uniquely, tethering plus MI showed endothelial activation with vascular adhesion molecule expression, neovascularization, and cells positive for CD45, considered a hematopoietic cell marker. Tethered plus MI findings were comparable with external ventricular constraint., Conclusions: MI altered leaflet adaptation, including a profibrotic increase in valvular cell activation, CD45-positive cells, and matrix turnover. Understanding cellular and molecular mechanisms underlying leaflet adaptation and fibrosis could yield new therapeutic opportunities for reducing ischemic MR., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Whether Barlow disease (BD) and fibroelastic deficiency (FED), the main causes of mitral valve prolapse (MVP), should be considered 2 distinct diseases remains unknown. Mitral valves from patients who required surgery for severe mitral regurgitation due to degenerative nonsyndromic MVP were analyzed. Intraoperative diagnosis of BD or FED was based on leaflet redundancy and thickness, number of segments involved, and annular dimension. The removed medial scallop of the posterior leaflet and attached chordae were used for histopathological and immunohistological assessment. Histologically, compared to normal controls (n = 3), BD (n = 14), and FED (n = 9) leaflets demonstrated an altered architecture and increased thickness. Leaflet thickness was greater and chordae thickness lower in BD than FED (P < 0.0001). In BD, increased thickness was owing to spongiosa expansion (proteoglycan accumulation) and intimal thickening on fibrosa and atrialis; in FED, local thickening was predominant on the fibrosa side, with accumulation of proteoglycan-like material around the chordae. Collagen accumulation was observed in FED leaflets and chords and decreased in BD. Fragmented elastin fibers were present in BD and FED; elastin decreased in BD but increased in FED leaflets and around chordae. Activated myofibroblasts accumulate in both diseased leaflets and chords, but more abundantly in FED chordae (P < 0.0001), independently of age, suggesting a role of these cells in chordal rupture. There were more CD34-positive cells in BD leaflets and in FED chordae (P < 0.01). In BD leaflets (but not chordae) proliferative Ki67-positive cells were more abundant (P < 0.01) and matrix metalloproteinase 2 levels were increased (P < 0.01) indicating tissue remodeling. Upregulation of transforming growth factor beta and pERK signaling pathways was evident in both diseases but more prominent in FED leaflets (continued on next page)(P < 0.001), with pERK upregulation in FED chordae (P < 0.0001). Most cellular and signaling markers were negligible in control valves. Quantitative immunohistopathological analyses demonstrated distinct changes between BD and FED valves: predominant matrix degradation in BD and increased profibrotic signaling pathways in FED, indicating that BD and FED are 2 different entities. These results may pave the way for genetic studies of MVP and development of preventive drug therapies., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Open in new tab Download slide OBJECTIVES Aortic root abscess can spread to include adjacent cardiac structures, including the central or intervalvular fibrous body and mitral valve. After radical debridement, complex surgical correction is needed. We describe the results of our mitral valve sparing approach. METHODS Between January 2004 and December 2020, 60 patients underwent operation for infective endocarditis of the aortic root with extension towards the mitral valve at 2 centres in the Netherlands. Early and late clinical and echocardiographic outcomes were studied. RESULTS Prosthetic valve endocarditis was present in 42 (70%) patients and emergent or salvage surgery was performed in 8 (13%) patients. After radical debridement of all infected tissue, mitral valve repair was feasible in 48 (80%) patients. Early mortality occurred in 11 (18%) patients while mechanical circulatory support was needed in 8 (13%) patients. At 10 years after surgery, the estimated reintervention-free survival rate was 51.9% (95% confidence interval 37.0–66.8%). Eight patients underwent reintervention; this was more common in patients who underwent aortic valve rather than root replacement and in patients in whom mitral valve repair was performed without ring annuloplasty. For 48 patients who underwent mitral valve repair, the estimated freedom from recurrent mitral regurgitation rate was 64.4% (95% confidence interval 40.1–88.7%) at 10 years after surgery. CONCLUSIONS Surgical intervention for extensive infective endocarditis of the aortic root is related to reasonable perioperative morbidity and mortality. Optimal surgical technique is crucial to lower the risk of late reintervention. Mitral valve repair is feasible in the majority of patients with satisfactory durability. [ABSTRACT FROM AUTHOR]