title: Left ventricular assist device in end-stage heart failure: persistence of structural myocyte damage after unloading. An immunohistochemical analysis of the contractile myofilaments.
abstract: OBJECTIVE
  We sought to evaluate the contractile proteins in cardiomyocytes of patients with end-stage heart failure (HF) before and after mechanical support with a left ventricular assist device (LVAD).
  
  
  BACKGROUND
  Improvement of myocyte dysfunction has been suggested after LVAD support.
  
  
  METHODS
  Fourteen patients' myocardial biopsies taken at the time of LVAD implantation and after explantation, at the time of heart transplantation, were processed for routine hematoxylin-eosin staining and immunohistochemistry using monoclonal antibodies against actin, myosin, tropomyosin, troponin C and T and titin. A grading scale from 1 (abnormal staining of all myocytes, no cross-striation) to 5 (normal fiber anatomy and striation) was used. The cross-sectional area of cardiomyocytes was also measured.
  
  
  RESULTS
  The cardiomyocytes' cross-sectional area decreased after support, from 519 +/- 94 microm(2) to 319 +/- 53 microm(2) (p < 0.001). Actin, tropomyosin, troponin C, troponin T and titin at the time of LVAD implantation showed widespread distortion of architecture; their grades were 1.4 +/- 0.6, 2.3 +/- 1.0, 2.1 +/- 0.9, 2.1 +/- 1.2 and 2.0 +/- 0.6, respectively. In contrast, myosin morphology was preserved (4.6 +/- 0.7). After LVAD support, actin, tropomyosin, troponin C, troponin T and titin showed improvement (grades 2.7 +/- 1.3 [p = 0.004], 3.2 +/- 1.2 [p = 0.021], 3.3 +/- 0.9 [p = 0.004], 3.0 +/- 1.1 [p = 0.048] and 3.1 +/- 0.9 [p = 0.001], respectively), but no normalization. The myosin pattern deteriorated slightly (3.6 +/- 1.6 [p = 0.058]).
  
  
  CONCLUSIONS
  After LVAD support, during a period of 213 +/- 135 days in patients with end-stage HF, despite a decrease in the size of the cardiomyocytes, severe structural myocyte damage persisted. This does not support complete recovery of myocyte histologic features.
authors.affiliation: Heart Lung Center Utrecht, Utrecht, The Netherlands. n.dejonge@azu.nl
authors.forename: Nicolaas
authors.initials: N
authors.lastname: de Jonge
authors.forename: Dick F
authors.initials: DF
authors.lastname: van Wichen
authors.forename: Marguerite E I
authors.initials: ME
authors.lastname: Schipper
authors.forename: Jaap R
authors.initials: JR
authors.lastname: Lahpor
authors.forename: Frits H J
authors.initials: FH
authors.lastname: Gmelig-Meyling
authors.forename: Etienne O
authors.initials: EO
authors.lastname: Robles de Medina
authors.forename: Roel A
authors.initials: RA
authors.lastname: de Weger
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry; D000328:Adult; D001706:Biopsy; D004396:Coloring Agents / Q000627:therapeutic use; D003285:Contractile Proteins / Q000032:analysis; D001026:Coronary Artery Bypass / Q000295:instrumentation; D005260:Female; D006325:Heart Atria / Q000166:cytology / Q000473:pathology / Q000601:surgery; D006333:Heart Failure / Q000473:pathology / Q000601:surgery*; D006352:Heart Ventricles / Q000473:pathology / Q000601:surgery*; D006353:Heart-Assist Devices; D006416:Hematoxylin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009206:Myocardium / Q000473:pathology; D019919:Prosthesis Implantation / Q000295:instrumentation
chemical_list: D004396:Coloring Agents; D003285:Contractile Proteins; D006416:Hematoxylin