title: Disruption of desmin-mitochondrial architecture in patients with regurgitant mitral valves and preserved ventricular function.
abstract: Recent studies have demonstrated improved outcomes in patients receiving early surgery for degenerative mitral regurgitation (MR) rather than adhering to conventional guidelines for surgical intervention. However, studies providing a mechanistic basis for these findings are limited.
  
  
  
  Left ventricular (LV) myocardium from 22 patients undergoing mitral valve repair for American Heart Association class I indications was evaluated for desmin, the voltage-dependent anion channel, α-B-crystallin, and α, β-unsaturated aldehyde 4-hydroxynonenal by fluorescence microscopy. The same was evaluated in 6 normal control LV autopsy specimens. Cardiomyocyte ultrastructure was examined by transmission electron microscopy. Magnetic resonance imaging with tissue tagging was performed in 55 normal subjects and 22 MR patients before and 6 months after mitral valve repair.
  
  
  
  LV end-diastolic volume was 1.5-fold (P < .0001) higher and LV mass-to-volume ratio was lower in MR (P = .004) hearts versus normal hearts and showed improvement 6 months after mitral valve surgery. However, LV ejection fraction decreased from 65% ± 7% to 52% ± 9% (P < .0001) and LV circumferential (P < .0001) and longitudinal strain decreased significantly below normal values (P = .002) after surgery. Hearts with MR had a 53% decrease in desmin (P < .0001) and a 2.6-fold increase in desmin aggregates (P < .0001) versus normal, along with substantial, intense perinuclear staining of α, β-unsaturated aldehyde 4-hydroxynonenal in areas of mitochondrial breakdown and clustering. Transmission electron microscopy demonstrated numerous electron-dense deposits, myofibrillar loss, Z-disc abnormalities, and extensive granulofilamentous debris identified as desmin-positive by immunogold transmission electron microscopy.
  
  
  
  Despite well-preserved preoperative LV ejection fraction, severe oxidative stress and disruption of cardiomyocyte desmin-mitochondrial sarcomeric architecture may explain postoperative LV functional decline and further supports the move toward earlier surgical intervention.
authors.affiliation: Department of Medicine, Division of Cardiovascular Disease, UAB.
authors.forename: Mustafa I
authors.initials: MI
authors.lastname: Ahmed
authors.affiliation: Department of Medicine, Division of Cardiovascular Disease, UAB.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Guichard
authors.affiliation: Department of Pathology, UAB.
authors.forename: Rajasekaran Namakkal
authors.initials: RN
authors.lastname: Soorappan
authors.affiliation: Department of Anesthesiology& Perioperative Medicine, UAB.
authors.forename: Shama
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Department of Anesthesiology& Perioperative Medicine, UAB.
authors.forename: Nithya
authors.initials: N
authors.lastname: Mariappan
authors.affiliation: Department of Anesthesiology& Perioperative Medicine, UAB.
authors.forename: Silvio
authors.initials: S
authors.lastname: Litovsky
authors.affiliation: Department of Veterans Affairs Medical Center, Birmingham (UAB), Alabama, USA.|Department of Medicine, Division of Cardiovascular Disease, UAB.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Gupta
authors.affiliation: Department of Veterans Affairs Medical Center, Birmingham (UAB), Alabama, USA.|Department of Medicine, Division of Cardiovascular Disease, UAB.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Lloyd
authors.affiliation: Auburn University School of Engineering, Auburn, Alabama, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Denney
authors.affiliation: Department of Veterans Affairs Medical Center, Birmingham (UAB), Alabama, USA.
authors.forename: Pamela Cox
authors.initials: PC
authors.lastname: Powell
authors.affiliation: Department of Biostatistics, UAB.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Aban
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, UAB.
authors.forename: James
authors.initials: J
authors.lastname: Collawn
authors.affiliation: Department of Veterans Affairs Medical Center, Birmingham (UAB), Alabama, USA.|Department of Surgery, Division of Thoracic and Cardiovascular Surgery, UAB.
authors.forename: James E
authors.initials: JE
authors.lastname: Davies
authors.affiliation: The Alfred Hospital and Monash University, Melbourne, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: McGiffin
authors.affiliation: Department of Veterans Affairs Medical Center, Birmingham (UAB), Alabama, USA.|Department of Medicine, Division of Cardiovascular Disease, UAB.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Dell'Italia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000378:metabolism; D003893:Desmin / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000378:metabolism*; D008944:Mitral Valve Insufficiency / Q000378:metabolism* / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000648:ultrastructure; D016896:Treatment Outcome; D016277:Ventricular Function, Left; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000378:metabolism
chemical_list: D000447:Aldehydes; C059215:CRYAB protein, human; D003893:Desmin; D050994:Voltage-Dependent Anion Channels; D038203:alpha-Crystallin B Chain; C027576:4-hydroxy-2-nonenal
keywords: cardiomyocyte; heart failure; mitochondria; mitral regurgitation