Mitral Valve Adaptation: Can We Win the Race?
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ABSTRACT:
SUBMITTER: Kim DH
PROVIDER: S-EPMC5890943 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
Publications
Mitral Valve Adaptation: Can We Win the Race?
Kim Dae-Hee DH Dal-Bianco Jacob P JP Aikawa Elena E Bischoff Joyce J Levine Robert A RA
Circulation. Cardiovascular imaging 20180401 4
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Project description:BackgroundIn 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.ObjectivesThe 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.MethodsTwenty-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.ResultsTethered 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.ConclusionsMI 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.
| S-EPMC5099077 | biostudies-literature
Project description:Evaluation of global expression patterns provides a molecular portrait of mitral valve disease, yields insight into the pathophysiologic aspects of DMVD, and identifies intriguing genes and pathways for further study. (Am J Vet Res 2006;67:1307–1318) Keywords: control vs diseased 4 controls( beagle crosses) and 4 affected (1 Daschund, 1 Lhasa apso, 2 miniature poodles)
2008-05-15 | E-GEOD-11460 | biostudies-arrayexpress
Project description:Aim: Test the hypothesis that 5HT receptors (5HTRs) signaling contributes to MVP pathophysiology. Methods and results: MV RNA was used for microarray analysis of MVP patients versus control, highlighting genes that indicate the involvement of 5HTR pathways and extracellular matrix remodeling in MVP. These canine MVP leaflets (N=5/group) showed 5HTR2B upregulation. Conclusion: In humans, MVP is associated with an upregulation in 5HTR2B expression and increased 5HT receptor signaling in the leaflets. 5HTR signaling is involved not only in previously reported 5HTrelated valvulopathies, but it is also involved in the pathological remodeling of MVP.
2018-01-29 | GSE109744 | GEO
Project description:Evaluation of global expression patterns provides a molecular portrait of mitral valve disease, yields insight into the pathophysiologic aspects of DMVD, and identifies intriguing genes and pathways for further study. (Am J Vet Res 2006;67:1307–1318) Keywords: control vs diseased
2008-05-15 | GSE11460 | GEO
Project description:OBJECTIVES:This study hypothesized that compensatory mitral leaflet area (MLA) adaptation occurs in patients with persistent atrial fibrillation (AF) without left ventricular (LV) dysfunction but has limitations that augment mitral regurgitation (MR). The study also explored whether asymmetrical annular dilation is matched by relative leaflet enlargement. BACKGROUND:Functional MR occurs in patients with AF and isolated annular dilation, but the relationship of MLA adaptation with annular area (AA) is unknown. METHODS:Three-dimensional echocardiographic images were acquired from 86 patients with quantified MR: 53 with nonvalvular persistent AF (23 MR+ with moderate or greater MR, 30 MR-) without LV dysfunction or dilation and 33 normal controls. Comprehensive 3-dimensional analysis included total diastolic MLA, adaptation ratios of MLA to annular area and MLA to leaflet closure area, and annular and tenting geometry. RESULTS:Total MLA was 22% larger in patients with AF than in controls, thus paralleling the increased AA. However, as AA increased, adaptive indices (MLA/AA ratio and ratio of MLA to closure area) plateaued, becoming lowest in MR+ patients (ratio of MLA to closure area = 1.63 ± 0.17 controls, 1.60 ± 0.11 MR-, 1.32 ± 0.10 MR+; p < 0.001). MR increased as the ratio of MLA to closure area decreased (R2 = 0.68; p < 0.001). The posterior-to-anterior MLA ratio remained constant, whereas the posterior-to-anterior mitral annulus perimeter increased (1.21 ± 0.16 controls, 1.32 ± 0.20 MR-, 1.46 ± 0.19 MR+; p < 0.001). Multivariate MR determinants were annular area, total MLA to closure area, and posterior-to-anterior perimeter ratios. CONCLUSIONS:MLA adaptively increases in AF with isolated annular dilation and normal LV function. This compensatory enlargement becomes insufficient with greater annular dilation, and the leaflets fail to match asymmetrical annular remodeling, thereby increasing MR. These findings can potentially help optimize therapeutic options and motivate basic studies of adaptive growth processes.
| S-EPMC5993562 | biostudies-literature
Project description:Mitral valve prolapse (MVP) is often benign but can progress to mitral regurgitation, requiring invasive treatment. In mgR mice with hypomorphic Fbn1 mutations—mimicking Marfan syndrome—myxomatous mitral degeneration and regurgitation develop by 12 weeks. TGF-β and mTOR signaling activation, along with macrophage infiltration, appear by 4 weeks, before histological changes. Short-term rapamycin treatment blocks early TGF-β activation and inflammation, while long-term mTOR or TGF-β inhibition rescues valve degeneration. Transcriptomics revealed integrins as upstream regulators of mTOR. Blocking integrin signaling or altering its pathway prevented mTOR activation. These findings are conserved in human MVP, suggesting that mTOR activation via abnormal integrin-matrix signaling drives disease and that mTOR inhibition may be a potential therapy.
2025-05-07 | GSE293926 | GEO
Project description:The risk of left ventricular (LV) and right ventricular (RV) maladaptation after surgery for isolated primary mitral regurgitation (PMR) is poorly defined. We aimed to evaluate LV and RV contractile function using speckle-tracking analysis alongside with quantification of exercise tolerance in patients with PMR after mitral valve surgery. All consecutive patients with symptomatic PMR undergoing mitral valve surgery between July 2015 and May 2017 were prospectively enrolled. Sequential echocardiographic studies along with clinical assessment were performed before and three months after surgery. Mean age in 138 patients was 65.8 ± 12.7 years, 48.2% (66) of whom were female. Mean LV ejection fraction decreased from 57 ± 12% to 50 ± 11% (p < 0.001), LV global longitudinal strain deteriorated from -19.2 ± 4.1% to -15.7 ± 3.8% (p < 0.001), and mechanical strain dispersion increased from 88 ± 12 to 117 ± 115 ms (p = 0.004). There was a reduction in tricuspid annulus plane systolic excursion from 22 ± 5 mm to 18 ± 4 mm (p < 0.001), as well as a slight deterioration of RV free wall mean longitudinal strain from -16.9 ± 5.6% to -15.7 ± 4.1% (p = 0.05). The rate of moderate to severe tricuspid regurgitation significantly decreased (p < 0.005). Regarding exercise tolerance, the New York Heart Association class improved (p < 0.001) and the walking distance increased (p < 0.001). During mid-term follow up after surgery for PMR, a deterioration of LV and RV contractile function measures could be observed. However, the clinical status, LV dimensions, and concomitant tricuspid regurgitation improved which in particular imply more effective RV contractile pattern.
| S-EPMC7969695 | biostudies-literature
Project description:ObjectiveIntraoperative predictors of functional mitral valve (MV) stenosis after surgical repair of mitral regurgitation (MR) caused by prolapse remain poorly characterised. This study evaluated the effect of annuloplasty size on postoperative MV haemodynamics during exercise and evaluated predictors of MV hemodynamics.Methods104 patients were randomly assigned to leaflet resection or preservation for surgical repair of MR in the Canadian Mitral Research Alliance CardioLink-2 study. In this post hoc analysis, we compared MV haemodynamics between the two surgical groups and examined the relationship between annuloplasty size and MV haemodynamics 1 year after repair in the combined groups. Echocardiograms were performed at baseline and intraoperatively. Exercise transthoracic echocardiography was performed 1 year postoperatively. Multivariable linear regression analysis was used to identify predictors of exercise MV gradients at follow-up.ResultsMean age of participants was 65±10 years, and 83% were male. Median annuloplasty size was 34 (IQR 32-36). Dividing by the median, 48 (46%) had annuloplasty size of <34 mm and 56 (54%) had ≥34 mm. Mean and peak exercise gradients at 1 year were 11±5 mm Hg and 22±9 mm Hg in <34, and 6±3 mm Hg and 14±5 mm Hg in ≥34 (p<0.001). Rate of residual MR was similar in both groups. In multivariable analyses, annuloplasty size of ≥34 mm was associated with lower mean and peak exercise gradients at 12 months, after adjustment for repair type, age, sex, heart rate and body surface area (β -4.1, 95% CI -6 to -3, p<0.001, and β -7 95% CI -10 to -4, p<0.001, respectively). Intraoperative mean and peak MV gradients by transesophageal echocardiography independently predicted mean and peak resting and exercise gradients at follow-up (p<0.001). Similar results were obtained in both leaflet resection and preservation.ConclusionAnnuloplasty size of ≥34 mm is associated with a 4 and 7 mm Hg reduction in mean and peak exercise MV gradients, respectively, 1 year post MV repair regardless of the repair strategy used. Intraoperative TEE MV gradients predict exercise MV gradients 1 year post repair.Trial registration numberNCT02552771.
| S-EPMC10314030 | biostudies-literature
Project description: Not available
| S-EPMC9896385 | biostudies-literature
Project description:ObjectivesThe present study aims to assess and describe the intracardiac blood flow dynamic in patients with mitral regurgitation (MR), repaired mitral valves (MV) and mitral valve prostheses using vector flow mapping (VFM).MethodsPatients with different MV pathologies and MV disease treatments were analysed. All patients underwent 2D transthoracic echocardiography, and images for flow visualization were acquired in VFM mode in an apical three-chamber view and four-chamber view. Vectors and vortices were qualitatively analyzed.Resultsthirty-two (32) patients underwent 2D transthoracic echocardiography (TTE) with VFM analysis. We evaluated intracardiac flow dynamics in 3 healthy subjects, 10 patients with MR (5 degenerative, 5 functional), 4 patients who underwent MV repair, 5 who underwent MV replacement (3 biological, 2 mechanical), 2 surgically implanted transcatheter heart valve (THV), 2 transcatheter edge-to-edge MV repair with MitraClip (TEER), 3 transcatheter MV replacement (TMVR) and 3 transapical off-pump MV repair with NeoChord implantation. Blood flow patterns are significantly altered in patients with MV disease and MV repair compared to control patients. MV repair is superior to replacement in restoring more physiologicalpatterns, while TMVR reproducesan intraventricular flowcloser to normal than surgical MVR and TEER.ConclusionsIntracardiac flow patterns can be clearly defined using VFM. Restoration of a physiological blood flow pattern inside the LV directly depends on the procedure used to address MV disease.
| S-EPMC10080047 | biostudies-literature