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Attenuated Mitral Leaflet Enlargement and Ischemic Mitral Regurgitation
Study Questions:
Does myocardial infarction (MI) impair mitral leaflet growth seen among patients with aortic regurgitation (AR) with left ventricular (LV) dilation, and induce fibrotic changes in the mitral valve and tricuspid valve?
Methods:
Sheep models of AR, AR + MI (with a small apical 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 (MR), and mitral leaflet size. Histopathology and molecular analyses were performed in excised valves.
Results:
Both experimental groups (AR, AR + MI) 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). MR 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 MR, despite similar LV size and function. More pronounced extracellular remodeling was observed in mitral and tricuspid leaflets, suggesting systematic valvular remodeling after MI.
Perspective:
Functional MR is predominantly caused by alterations in LV size and geometry. Although the compensatory changes are variable and not well understood, LV dilation can be accompanied by mitral leaflet enlargement, in some patients mitigating the development of functional MR. This animal model study found that the presence of a small apical MI in addition to AR was associated with less compensatory mitral leaflet enlargement compared to animals with only AR, and an associated increase in functional MR severity despite similar changes in LV size and systolic function. In addition, animals with MI plus AR had thicker leaflets with increased extracellular remodeling. This suggests that functional MR occurs when there is both LV enlargement and a lack of compensatory mitral leaflet enlargement, and that a small apical MI can prevent mitral leaflet enlargement. Additional study might further elucidate the factors that affect mitral leaflet compensatory enlargement, providing potential targets for future therapies to diminish the development of functional MR.
Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Valvular Heart Disease, Echocardiography/Ultrasound, Magnetic Resonance Imaging, Mitral Regurgitation
Keywords: Aortic Valve Insufficiency, Dilatation, Diagnostic Imaging, Echocardiography, Extracellular Matrix, Heart Valve Diseases, Hypertrophy, Left Ventricular, Magnetic Resonance Imaging, Mitral Valve Insufficiency, Myocardial Infarction, Systole, Tomography, Tricuspid Valve
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