Author + information
- Received October 15, 2019
- Revision received November 8, 2019
- Accepted November 13, 2019
- Published online January 27, 2020.
- Ons Marsit, MSca,
- Marie-Annick Clavel, DVM, PhDa,
- Claudia Côté-Laroche, MDa,
- Sandra Hadjadj, MSca,
- Marc-André Bouchard, MDa,
- Mark D. Handschumacher, BSb,
- Marine Clisson, MSca,
- Marie-Claude Drolet, MSca,
- Marie-Chloé Boulanger, PhDa,
- Dae-Hee Kim, MD, PhDc,
- J. Luis Guerrero, BSd,
- Philipp Emanuel Bartko, MDd,
- Jacques Couet, PhDa,
- Marie Arsenault, MDa,
- Patrick Mathieu, MD, MSca,
- Philippe Pibarot, DVM, PhDa,
- Elena Aïkawa, MD, PhDd,
- Joyce Bischoff, PhDe,
- Robert A. Levine, MDd and
- Jonathan Beaudoin, MDa,∗ (, )@universitelaval
- aInstitut Universitaire de Cardiologie et de Pneumologie de Québec–Université Laval, Québec City, Quebec, Canada
- bCenter for Excellence in Vascular Biology, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- cDivision of Cardiology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea
- dCardiac Ultrasound Lab, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- eVascular Biology Program and Department of Surgery, Boston Children’s Hospital and Department of Surgery, Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Jonathan Beaudoin, Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Sainte-Foy, Québec City, Québec G1V4G5, Canada.
Background Mitral leaflet enlargement has been identified as an adaptive mechanism to prevent mitral regurgitation in dilated left ventricles (LVs) caused by chronic aortic regurgitation (AR). This enlargement is deficient in patients with functional mitral regurgitation, which remains frequent in the population with ischemic cardiomyopathy. Maladaptive fibrotic changes have been identified in post-myocardial infarction (MI) mitral valves. It is unknown if these changes can interfere with valve growth and whether they are present in other valves.
Objectives This study sought to test the hypothesis that MI impairs leaflet growth, seen in AR, and induces fibrotic changes in mitral and tricuspid valves.
Methods Sheep models of AR, AR + MI, and controls were followed for 90 days. Cardiac magnetic resonance, echocardiography, and computed tomography were performed at baseline and 90 days to assess LV volume, LV function, mitral regurgitation and mitral leaflet size. Histopathology and molecular analyses were performed in excised valves.
Results Both experimental groups developed similar LV dilatation and dysfunction. At 90 days, mitral valve leaflet size was smaller in the AR + MI group (12.8 ± 1.3 cm2 vs. 15.1 ± 1.6 cm2, p = 0.03). Mitral regurgitant fraction was 4% ± 7% in the AR group versus 19% ± 10% in the AR + MI group (p = 0.02). AR + MI leaflets were thicker compared with AR and control valves. Increased expression of extracellular matrix remodeling genes was found in both the mitral and tricuspid leaflets in the AR + MI group.
Conclusions In these animal models of AR, the presence of MI was associated with impaired adaptive valve growth and more functional mitral regurgitation, despite similar LV size and function. More pronounced extracellular remodeling was observed in mitral and tricuspid leaflets, suggesting systemic valvular remodeling after MI.
This work has been funded by the Heart and Stroke Foundation of Canada (GIA G-15-0008860), Canadian Institutes for Health Research (399323), and Fonds de Recherche Santé-Québec (to Dr. Beaudoin). Dr. Clavel has had a Core Laboratory contract with Edwards Lifesciences; and has received a research grant from Medtronic. Dr. Pibarot has had Echo Core Laboratory contracts with Cardiac Phoenix and Edwards Lifesciences. Dr. Aïkawa has received grants from the National Institutes of Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received October 15, 2019.
- Revision received November 8, 2019.
- Accepted November 13, 2019.
- 2020 American College of Cardiology Foundation
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