Abstract 5871: Chronic Organic Mitral Regurgitation Results in Myofibrillar Degeneration and Oxidative Stress with Post-Surgical Left Ventricular Impairment Despite Pre-Surgical Left Ventricular Ejection Fraction > 60%

Abstract

Background: Current guidelines recommend valve repair for chronic organic mitral regurgitation (MR) if LVEF drops below 60% to preserve LV function and maximize outcome. Post-operative drop in LVEF is typical, and widely believed to be due to alteration in loading conditions. Here we address whether cardiomyocyte damage may contribute to postoperative dysfunction. Methods: Three-dimensional magnetic resonance imaging (3D-MRI) with tissue tagging was performed in 23 MR patients, prior to and six months following mitral valve repair. LV biopsy was obtained from all MR patients at time of surgery. Immunohistochemistry was performed to assess for signs of oxidative stress, specifically lipofuscin deposition, and presence and quantity of xanthine oxidase (XO). Plasma XO levels were measured before, and six months post-surgery. Results: MR patients (n=23) demonstrated decreased LVEF (62 ± 1 to 54 ± 2% p=0.0002) and LV end-diastolic volume (116 ± 5 to 79 ± 5 ml/m 2 p<0.0001) six months after mitral valve (MV) repair. LV circumferential and longitudinal strain rates decreased below normal (6.54 ± 0.21 vs. 5.24 ± 0.24 p=0.0001, and 6.56 ± 0.26 vs. 5.41 ± 0.27 p=0.0084) despite no change in blood pressure and 3-dimensional LV end-systolic radius/wall thickness ratios. LV biopsies demonstrated marked cardiomyocyte myofibrillar degeneration vs. normals (2.32 ± 1.09 vs. 1.25 ± 0.45, p=0.0016, mean degeneration grade [1–4]). Immunostaining for xanthine oxidase (XO), a prominent oxidative enzyme, was increased in MR vs. normals (88 ± 7 vs. 33 ± 4%, p <0.01), as plasma XO decreased post-MV repair (2.12 ± 0.46 to 0.49 ± 0.25 μU/mL, p=0.008). Lipofuscin deposition, a product of oxidative stress, was increased in cardiomyocytes of MR vs. normals (0.62 ± 0.04 vs. 0.33 ± 0.04%, p <0.01). Conclusions: Decreased LV strain rates 6 months post MV repair indicate myocyte contractile dysfunction in chronic MR patients despite pre-surgical LVEF >60%. This is supported by marked cardiomyocyte myofibrillar degeneration and oxidative damage at the time of surgery. While raising questions regarding timing of surgery for MR, these findings generate hypothesis concerning XO and oxidative stress-related myocyte damage in the pathophysiology of LV contractile dysfunction in MR.