Dataset Information

Image-Guided Targeted Mitral Valve Tethering with Chordal Encircling Snares as a Preclinical Model of Secondary Mitral Regurgitation.

ABSTRACT: Development of transcatheter mitral valve interventions has ushered a significant need for large animal models of secondary mitral regurgitation. Though currently used heart failure models that chronically develop secondary mitral regurgitation are viable, the severity is lower than patients, the incubation time is long, and mortality is high. We sought to develop a swine model of acute secondary mitral regurgitation that uses image-guided placement of snares around the mitral chordae. Twenty-seven adult swine (n = 27) were assigned to secondary mitral regurgitation induced by valve tethering with image-guided chordal encircling snares (group 1, n = 7, tether MR (tMR)); secondary mitral regurgitation by percutaneous posterolateral myocardial infarction causing ventricular dysfunction and regurgitation (group 2, n = 6, functional MR (fMR)); and control animals (group 3, n = 14). Regurgitant fraction in tMR was 42.1 ± 14.2%, in fMR was 22 ± 9.6%, and in controls was 5.3 ± 3.8%. Mitral tenting height was 9.6 ± 1.3 mm in tMR, 10.1 ± 1.5 mm in fMR, and 5.8 ± 1.2 mm in controls. Chordal encircling tethers reproducibly induce clinically relevant levels of secondary mitral regurgitation, providing a new animal model for use in translational research.

SUBMITTER: Onohara D

PROVIDER: S-EPMC10797638 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Image-Guided Targeted Mitral Valve Tethering with Chordal Encircling Snares as a Preclinical Model of Secondary Mitral Regurgitation.

Onohara Daisuke D Suresh Kirthana Sreerangathama KS Silverman Michael M He Qi Q Kono Takanori T Padala Muralidhar M

Journal of cardiovascular translational research 20211007 3

Development of transcatheter mitral valve interventions has ushered a significant need for large animal models of secondary mitral regurgitation. Though currently used heart failure models that chronically develop secondary mitral regurgitation are viable, the severity is lower than patients, the incubation time is long, and mortality is high. We sought to develop a swine model of acute secondary mitral regurgitation that uses image-guided placement of snares around the mitral chordae. Twenty-se ...[more]

PMID: 34618333

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

Project description:ObjectivesThe Cardiothoracic Surgical Trials Network recently reported no difference in the primary end point of left ventricular end-systolic volume index at 1 year postsurgery in patients randomized to repair (n = 126) or replacement (n = 125) for severe ischemic mitral regurgitation. However, patients undergoing repair experienced significantly more recurrent mitral regurgitation than patients undergoing replacement (32.6% vs 2.3%). We examined whether baseline echocardiographic and clinical characteristics could identify those who will develop moderate/severe recurrent mitral regurgitation or die.MethodsOur analysis includes 116 patients who were randomized to and received mitral valve repair. Logistic regression was used to estimate a model-based probability of recurrence or death from baseline factors. Receiver operating characteristic curves were constructed from these estimated probabilities to determine classification cut-points maximizing accuracy of prediction based on sensitivity and specificity.ResultsOf the 116 patients, 6 received a replacement before leaving the operating room; all other patients had mild or less mitral regurgitation on intraoperative echocardiogram after repair. During the 2-year follow-up period, 76 patients developed moderate/severe mitral regurgitation or died (53 mitral regurgitation recurrences, 13 mitral regurgitation recurrences and death, and 10 deaths). The mechanism for recurrent mitral regurgitation was largely mitral valve leaflet tethering. Our model (including age, body mass index, sex, race, effective regurgitant orifice area, basal aneurysm/dyskinesis, New York Heart Association class, history of coronary artery bypass grafting, percutaneous coronary intervention, or ventricular arrhythmias) yielded an area under the receiver operating characteristic curve of 0.82.ConclusionsThe model demonstrated good discrimination in identifying patients who will survive 2 years without recurrent mitral regurgitation after mitral valve repair. Although our results require validation, they offer a clinically relevant risk score for selection of surgical candidates for this procedure.

Dataset Information

Image-Guided Targeted Mitral Valve Tethering with Chordal Encircling Snares as a Preclinical Model of Secondary Mitral Regurgitation.

Publications

Image-Guided Targeted Mitral Valve Tethering with Chordal Encircling Snares as a Preclinical Model of Secondary Mitral Regurgitation.

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