Abstract

Mitral valve (MV) fibrosis and thickening have been described after myocardial infarction (MI), potentially contributing to ischemic mitral regurgitation. There is currently no imaging tool available to explore those changes. MV late gadolinium enhancement (LGE) has been observed retrospectively in post-MI patients with cardiac magnetic resonance (CMR), potentially reflecting MV fibrotic changes. However, MV LGE has never been validated with histopathology. Baseline CMR was performed in 16 sheep. Mid-systolic MV LGE was assessed by CMR (200 milliseconds after QRS to avoid rapid leaflet motion during the acquisition). Metoprolol was given as needed when heart rate was over 100 beats per minute. Inferior MI was induced by surgical coronary ligation in 13 sheep; the survivors (n=9) had repeated CMR 3 months after MI, followed by sacrifice. Three normal animals were used as controls. MV LGE signal was correlated with MV thickness (microscopy) and collagen content (Masson Trichrome). Post-MI sheep had mild decrease in left ventricle ejection fraction (51±4 vs 61±9% at baseline, p=0.02). Among post-MI animals, 3/9 (33%) developed significant (greater than mild) mitral regurgitation. MV LGE was present in 2/16 (13%) sheep at baseline vs 6/9 (66%) after MI (p=0.02). MV LGE was present in all (3/3) post-MI sheep with mitral regurgitation at follow-up, vs 3/6 (50%) of post-MI sheep without regurgitation. By microscopy, post-MI sheep had thicker MV leaflets (p < 0.01), with more collagen positive areas (normalized for leaflet length) vs controls (364±91 vs 195±49 μm2/μm, p=0.01). MV showing LGE were significantly thicker (1057±240 μm vs 656 ±197 μm for those without LGE, p=0.003). In this animal model, MI was associated with thicker mitral valves with increased collagen. Presence of MV LGE was associated with increased MV thickness and all animals with post-MI mitral regurgitation had positive LGE. Development of non-invasive tools to identify MV fibrotic changes can enable the exploration of MV fibrosis in clinical studies.

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