title: Increased oxidative stress and cardiomyocyte myofibrillar degeneration in patients with chronic isolated mitral regurgitation and ejection fraction >60%.
abstract: OBJECTIVE
  This study assessed myocardial damage in patients with chronic isolated mitral regurgitation (MR) and left ventricular ejection fraction (LVEF) >60%.
  
  
  BACKGROUND
  Typically, MR patients have decreased LVEF after mitral valve (MV) repair despite normal pre-operative LVEF.
  
  
  METHODS
  Twenty-seven patients with isolated MR had left ventricular (LV) biopsies taken at time of MV repair. Magnetic resonance imaging with tissue tagging was performed in 40 normal subjects and in MR patients before and 6 months after MV repair.
  
  
  RESULTS
  LVEF (66 +/- 5% to 54 +/- 9%, p < 0.0001) and LV end-diastolic volume index (108 +/- 28 ml/m(2) to 78 +/- 24 ml/m(2), p < 0.0001) decreased, whereas left ventricular end-systolic (LVES) volume index was 60% above normal pre- and post-MV repair (p < 0.05). The LV circumferential and longitudinal strain rates decreased below normal following MV repair (6.38 +/- 1.38 vs. 5.11 +/- 1.28, p = 0.0009, and 7.51 +/- 2.58 vs. 5.31 +/- 1.61, percentage of R to R interval, p < 0.0001), as LVES stress/LVES volume index ratio was depressed at baseline and following MV repair versus normal subjects (0.25 +/- 0.10 and 0.28 +/- 0.05 vs. 0.33 +/- 0.12, p < 0.01). LV biopsies demonstrated cardiomyocyte myofibrillar degeneration versus normal subjects (p = 0.035). Immunostaining and immunoblotting demonstrated increased xanthine oxidase in MR versus normal subjects (p < 0.05). Lipofuscin deposition was increased in cardiomyocytes of MR versus normal subjects (0.62 +/- 0.20 vs. 0.33 +/- 0.11, percentage of area: p < 0.01).
  
  
  CONCLUSIONS
  Decreased LV strain rates and LVES wall stress/LVES volume index following MV repair indicate contractile dysfunction, despite pre-surgical LVEF >60%. Increased oxidative stress could cause myofibrillar degeneration and lipofuscin accumulation resulting in LV contractile dysfunction in MR.
authors.affiliation: Center for Heart Failure Research, Departments of Medicine, Cardiovascular Surgery, Pathology, and Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama 35294-2180, USA.
authors.forename: Mustafa I
authors.initials: MI
authors.lastname: Ahmed
authors.forename: James D
authors.initials: JD
authors.lastname: Gladden
authors.forename: Silvio H
authors.initials: SH
authors.lastname: Litovsky
authors.forename: Steven G
authors.initials: SG
authors.lastname: Lloyd
authors.forename: Himanshu
authors.initials: H
authors.lastname: Gupta
authors.forename: Seidu
authors.initials: S
authors.lastname: Inusah
authors.forename: Thomas
authors.initials: T
authors.lastname: Denney
authors.forename: Pamela
authors.initials: P
authors.lastname: Powell
authors.forename: David C
authors.initials: DC
authors.lastname: McGiffin
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Dell'Italia
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008062:Lipofuscin / Q000378:metabolism; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000503:physiopathology* / Q000601:surgery; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology*; D011184:Postoperative Period; D057234:Preoperative Period; D013318:Stroke Volume / Q000502:physiology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D008062:Lipofuscin; C002744:3-nitrotyrosine; D014443:Tyrosine; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase