scholarly journals Mitral valve leaflet response to ischemic mitral regurgitation: From gene expression to tissue remodeling

2019 ◽  
Author(s):  
Daniel P. Howsmon ◽  
Bruno V. Rego ◽  
Estibaliz Castillero ◽  
Salma Ayoub ◽  
Amir H. Khalighi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Extracellular Matrix ◽  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Rna Sequencing ◽  
Immune Cells ◽  
Ischemic Mitral Regurgitation ◽  
Post Myocardial Infarction ◽  
Mechanical Anisotropy

AbstractAimsIschemic mitral regurgitation is frequently observed following myocardial infarction and is associated with higher mortality and poor clinical prognosis if left untreated. Accumulating evidence suggests that mitral valve leaflets actively remodel post–myocardial infarction, yet the cellular mechanisms underlying these responses and how this affects tissue function remain largely unknown. We sought to elucidate mitral valve remodeling post myocardial infarction at the tissue, cellular, and transcriptomic levels.Methods and ResultsThe mechanical behavior of ovine mitral valve leaflets pre– and 8 weeks post– myocardial infarction reveal a significant decrease in radial direction extensibility, which essentially eliminated the mechanical anisotropy typically observed in healthy mitral valves. Quantitative histology and ultrastructural assessment by transmission electron microscopy revealed altered leaflet composition and architecture at 8 weeks post–myocardial infarction. Assessment of the mitral valve interstitial cell nuclear aspect ratio, a metric of cellular deformation, revealed that they were on average rounder following myocardial infarction. RNA sequencing indicated that YAP-induced genes were elevated at 4 weeks post–myocardial infarction and genes related to extracellular matrix organization were some of the most downregulated in sheep with IMR compared to sheep without ischemic mitral regurgitation at 4 weeks post–myocardial infarction. Additionally, RNA sequencing revealed the possible recruitment of immune cells in this remodeling process due to the drastic elevation of CXCL9 and CLEC10A.ConclusionsOur multiscale assessment revealed significant mechanical and microstructural changes due to myocardial infarction. RNA sequencing provided a baseline for global gene expression changes in response to myocardial infarction with and without ischemic mitral regurgitation and suggests YAP-induced mechanotransduction, altered expression of extracellular matrix–related genes, and recruitment of immune cells as mechanisms contributing to altered mitral valve biomechanics post–myocardial infarction.

scholarly journals Transventricular Mitral Valve Repair in Patients with Acute Forms of Ischemic Mitral Regurgitation

2014 ◽  
Vol 41 (3) ◽  
pp. 312-315 ◽  
Author(s):  
Kerim Cagli ◽  
Hikmet Selcuk Gedik ◽  
Kemal Korkmaz ◽  
Baran Budak ◽  
Umit Yener ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Mitral Valve Repair ◽  
Mitral Valve Surgery ◽  
Left Ventricular ◽  
Ischemic Mitral Regurgitation ◽  
Post Myocardial Infarction ◽  
Valve Repair ◽  
Left Ventricular Restoration

Transventricular mitral valve surgery combined with left ventricular restoration avoids atriotomy and provides a larger operative field. We describe a series of 5 patients in whom we performed transventricular mitral valve repair by various techniques, such as band annuloplasty, papillary muscle reattachment, chordal cutting, and edge-to-edge repair. The more acute forms of ischemic mitral regurgitation, as found in our patients, can coexist with post-myocardial infarction contained rupture or post-myocardial infarction ventricular septal rupture. Because these patients already have an indication for ventriculotomy, concomitant transventricular repair of the mitral valve can render a separate atriotomy unnecessary and thereby shorten the duration of cardiopulmonary bypass. Moreover, in patients with acute presentations, the absence of atrial dilation (this last associated with chronic cases) might make transventricular repair a better choice than the more difficult atrial approach.

scholarly journals Mechanisms and predictors of ischemic mitral regurgitation at rest and on exertion in patients at early stage of myocardial infarction

2020 ◽  
Vol 25 (2) ◽  
pp. 52-59
Author(s):  
K. G. Adamyan ◽  
A. L. Chilingaryan ◽  
N. G. Mkrtchyan ◽  
L. G. Tunyan
Keyword(s):  
Myocardial Infarction ◽  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Early Stage ◽  
Physical Exertion ◽  
Ischemic Mitral Regurgitation ◽  
Mitral Orifice ◽  
Lv Volume ◽  
And Function

Aim. Determination of the mechanisms and predictors of ischemic mitral regurgitation (IMR) at rest and on exertion in patients at early stage of myocardial infarction (MI).Material and methods. Seventy-seven patients with inferoposterior MI and 79 patients with anteroseptal apical MI were examined on the 7th day at rest and after exertion. We determined the degree of IMR (according to the PISA method), posteromedial and anterolateral papillary muscle (PM) displacement, closure height of the mitral valve (MV), systolic and diastolic mitral valve orifice area, volume of the left ventricle (LV), LV contractility index, deformation of the infarction regions, general LV deformation, deformation and systolic dyssinchrony of the PM.Results. IMR was more common in inferior MI (42% vs 28%). LV volumes in cases with anteroseptal apical MI and IMR were greater and LV deformation was less than in patients without IMR. In inferoposterior MI and IMR, differences were observed in the index of local contractility and function of the posteromedial PM. The differences in MI of both localizations and IMR compared with MI without IMR were the areas of the mitral orifice and dyssinchrony of the PM. The degree of IMR after exertion did not depend on the degree of IMR at rest. Predictors of IMR at rest in MI of both localizations were the apical displacement of MV closure and the area of the mitral orifice. In inferoposterior, posteromedial PM displacement, deformation of the infarcted areas, PM dyssinchrony were also predictors. In anteroseptal apical MI, the area of the mitral orifice was the predictor of IMR. Predictors of anteroseptal apical MI after physical exertion after inferior MI were mitral orifice areas, contractility index, displacement and deformation of the posteromedial PM. In anteroseptal apical MI, the IMR predictors were MV closure height and systolic area of mitral orifice.Conclusion. The study confirms the significance of changing the spatial orientation of the MV structures in MI of both localizations, impaired regional contractility in inferoposterior MI and LV volume in anteroseptal apical MI at early stage of the disease.

scholarly journals Left atrial geometry in an ovine ischemic mitral regurgitation model: implications for transcatheter mitral valve replacement devices with a left atrial anchoring mechanism

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Akito Imai ◽  
Arash Khamooshian ◽  
Keitaro Okamoto ◽  
Yoshiaki Saito ◽  
Inez J. Wijdh-den Hamer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Valve Replacement ◽  
Mitral Valve Replacement ◽  
Left Atrial ◽  
Left Ventricular ◽  
Ischemic Mitral Regurgitation ◽  
Device Development ◽  
Transcatheter Mitral Valve Replacement

Abstract Background Transcatheter mitral valve replacement (TMVR) is a challenging, but promising minimally invasive treatment option for patients with mitral valve disease. Depending on the anchoring mechanism, complications such as mitral leaflet or chordal disruption, aortic valve disruption or left ventricular outflow tract obstruction may occur. Supra-annular devices only anchor at the left atrial (LA) level with a low risk of these complications. For development of transcatheter valves based on LA anchoring, animal feasibility studies are required. In this study we sought to describe LA systolic and diastolic geometry in an ovine ischemic mitral regurgitation (IMR) model using magnetic resonance imaging (MRI) and echocardiography in order to facilitate future research focusing on TMVR device development for (I)MR with LA anchoring mechanisms. Methods A group of 10 adult male Dorsett sheep underwent a left lateral thoracotomy. Posterolateral myocardial infarction was created by ligation of the left circumflex coronary artery, the obtuse marginal and diagonal branches. MRI and echocardiography were performed at baseline and 8 weeks after myocardial infarction (MI). Results Six animals survived to 8 weeks follow-up. All animals had grade 2 + or higher IMR 8 weeks post-MI. All LA geometric parameters did not change significantly 8 weeks post-MI compared to baseline. Diastolic and systolic interpapillary muscle distance increased significantly 8 weeks post-MI. Conclusions Systolic and diastolic LA geometry do not change significantly in the presence of grade 2 + or higher IMR 8 weeks post-MI. These findings help facilitate future tailored TMVR device development with LA anchoring mechanisms.

scholarly journals Mitral valve leaflet response to ischaemic mitral regurgitation: from gene expression to tissue remodelling

2020 ◽  
Vol 17 (166) ◽  
pp. 20200098
Author(s):  
Daniel P. Howsmon ◽  
Bruno V. Rego ◽  
Estibaliz Castillero ◽  
Salma Ayoub ◽  
Amir H. Khalighi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Collagen Fibre ◽  
Mechanical Anisotropy ◽  
Radial Deformation ◽  
Tissue Remodelling ◽  
Mitral Valve Leaflet ◽  
Clinical Prognosis ◽  
Transcriptomic Changes

Ischaemic mitral regurgitation (IMR), a frequent complication following myocardial infarction (MI), leads to higher mortality and poor clinical prognosis if untreated. Accumulating evidence suggests that mitral valve (MV) leaflets actively remodel post MI, and this remodelling increases both the severity of IMR and the occurrence of MV repair failures. However, the mechanisms of extracellular matrix maintenance and modulation by MV interstitial cells (MVICs) and their impact on MV leaflet tissue integrity and repair failure remain largely unknown. Herein, we sought to elucidate the multiscale behaviour of IMR-induced MV remodelling using an established ovine model. Leaflet tissue at eight weeks post MI exhibited significant permanent plastic radial deformation, eliminating mechanical anisotropy, accompanied by altered leaflet composition. Interestingly, no changes in effective collagen fibre modulus were observed, with MVICs slightly rounder, at eight weeks post MI. RNA sequencing indicated that YAP-induced genes were elevated at four weeks post MI, indicating elevated mechanotransduction. Genes related to extracellular matrix organization were downregulated at four weeks post MI when IMR occurred. Transcriptomic changes returned to baseline by eight weeks post MI. This multiscale study suggests that IMR induces plastic deformation of the MV with no functional damage to the collagen fibres, providing crucial information for computational simulations of the MV in IMR.

scholarly journals Reduced longitudinal contraction is associated with ischemic mitral regurgitation after posterior MI

2018 ◽  
Vol 314 (2) ◽  
pp. H322-H329 ◽  
Author(s):  
Kiyotake Ishikawa ◽  
Shin Watanabe ◽  
Nadjib Hammoudi ◽  
Jaume Aguero ◽  
Olympia Bikou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Longitudinal Strain ◽  
Left Ventricular ◽  
Ischemic Mitral Regurgitation ◽  
Circumflex Artery ◽  
Longitudinal Contraction ◽  
Diagonal Branch ◽  
Left Circumflex Artery

The role of left ventricular (LV) longitudinal contraction in ischemic mitral regurgitation (MR) remains unclear. We hypothesized that reduced longitudinal contraction disrupts normal mitral valve plane displacement during systole and leads to mitral valve tethering, thereby inducing ischemic MR. Twenty-three Yorkshire pigs underwent induction of different-sized posterior myocardial infarction (MI) using a percutaneous approach. The incidence of MR and its association with LV longitudinal strain were examined using speckle-tracking echocardiography at 1 mo post-MI to determine their relationship. A total of 17 pigs survived MI and completed the study. Pigs developed no more than mild MR after proximal left circumflex artery (LCx) occlusion (LCx group; n = 7). Addition of a first diagonal branch (D1) occlusion to LCx-MI (LCx + D1 group; n = 7) resulted in moderate to severe MR development 1 mo post-MI. LCx + D1 animals had lower longitudinal strain compared with the LCx group, whereas circumferential strain and LV rotation did not differ significantly. Posterolateral annular displacement toward the apex was significantly reduced in LCx + D1 animals, whereas the septal annular displacement was similar, suggesting an asymmetric mitral annular plane excursion in the LCx + D1 group. To exclude the contribution of papillary muscle infarction in MR development in our model, three pigs underwent obtuse marginal branch + D1 occlusion. None of these pigs developed significant MR after 1 mo. In conclusion, reduced longitudinal contraction contributes to the development of ischemic MR in a large posterior MI. NEW & NOTEWORTHY In this study, using our unique swine models of different-sized myocardial infarction, we showed, for the first time, that reduced longitudinal contraction contributes to the development of ischemic mitral regurgitation in a large posterior myocardial infarction. Our study adds new insights into the mechanisms of ischemic mitral regurgitation pathophysiology.

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