Key result
Tachycardia-induced cardiomyopathy in sheep increased mitral regurgitation (0.2 to 2.2; P<0.0002) and caused significant leaflet remodeling with increased matrix turnover versus controls (P<0.05).
Why the study?
Does tachycardia-induced cardiomyopathy alter matrix composition and turnover in mitral valve leaflets in a sheep model?
Does tachycardia-induced cardiomyopathy alter matrix composition and turnover in mitral valve leaflets in a sheep model?
p-value: p=<0.05
In a sheep model, tachycardia-induced cardiomyopathy causes significant structural and compositional remodeling of mitral valve leaflets, highlighting the role of altered mechanics in extracellular matrix changes.
Suggests mechanical drivers of mitral leaflet remodeling in sheep; leaves open translation to human functional MR.
BACKGROUND: Dilated cardiomyopathy (DCM) involves significant remodeling of the left ventricular-mitral valve (MV) complex, but little is known regarding the remodeling of the mitral leaflets. The aim of this study was to assess changes in matrix composition and turnover in MV leaflets with DCM. METHODS AND RESULTS: Radiopaque markers were implanted in 24 sheep to delineate the MV; 10 sheep underwent tachycardia-induced cardiomyopathy (TIC), whereas 14 sheep remained as controls. Biplane videofluoroscopy was performed before and after TIC. Immunohistochemistry was performed on leaflet cross-sections taken from the septal, lateral, anterior, and posterior commissures attachment segments. Staining intensity was quantified within each attachment segment and leaflet region (basal, mid-leaflet, and free edge). Mitral regurgitation increased from 0.2+/-0.4 before TIC to 2.2+/-0.9 after TIC (P<0.0002). TIC leaflets demonstrated significant remodeling compared to controls, including greater cell density and loss of leaflet layered structure (all P<0.05). Collagen and elastic fiber turnover was greater in TIC, as was the myofibroblast phenotype (all P<0.05). Compositional differences between TIC and control leaflets were heterogeneous by annular segment and leaflet region, and related to regional changes in leaflet segment length with TIC. CONCLUSIONS: This study shows that the MV leaflets are significantly remodeled in DCM with changes in leaflet composition, structure, and valve cell phenotype. Understanding how alterations in leaflet mechanics, such as those induced by DCM, drive cell-mediated remodeling of the extracellular matrix will be important in developing future treatment strategies.
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Stephens et al. (2009) studied Tachycardia-induced cardiomyopathy / Dilated cardiomyopathy (n=24). Tachycardia-induced cardiomyopathy (TIC) vs. Healthy controls was evaluated on Mitral valve leaflet remodeling (matrix composition and turnover) (p=<0.05). Tachycardia-induced cardiomyopathy in sheep increased mitral regurgitation (0.2 to 2.2; P<0.0002) and caused significant leaflet remodeling with increased matrix turnover versus controls (P<0.05).