title: Cardiomyocyte apoptosis and progression of heart failure to transplantation.
abstract: BACKGROUND
  Cardiomyocyte apoptosis has been found in congestive heart failure, but its clinical significance has been difficult to study. We compared the occurrence of cardiomyocyte apoptosis in explanted hearts with the progression of severe heart failure until the need for transplantation.
  
  
  METHODS
  Using the TUNEL assay, apoptotic cardiomyocytes were quantified in explanted failing hearts from patients with either idiopathic dilated cardiomyopathy (n = 21) or ischaemic heart disease (n = 14). The percentage was compared with the clinical severity and progression of endstage heart failure. Samples obtained at autopsy and during open heart surgery served as controls.
  
  
  RESULTS
  The number of apoptotic cardiomyocytes was significantly increased in failing hearts regardless of aetiology (medians 0.075% in ischaemic heart disease and 0.119% in dilated cardiomyopathy) compared with control myocardium. In patients with dilated cardiomyopathy, apoptotic cardiomyocytes were more numerous in subjects with a rapidly deteriorating clinical course (0.192%, n = 10) than in patients with intermediate (0.093%, n = 6, P = 0.03) or slow (0.026%, n = 5, P = 0.003) progression. No such association was observed in patients with ischaemic heart disease, in whom we found significantly increased cardiomyocyte apoptosis adjacent to scars of previous infarctions (0.576%) in contrast to the diffuse distribution seen in dilated cardiomyopathy. Expression of Bcl-2, an antiapoptotic protein, was increased in all failing hearts by immunohistochemistry.
  
  
  CONCLUSIONS
  Cardiomyocyte apoptosis is a consistent feature of end-stage heart failure in man and appears to be quantitatively related to the clinical severity of deterioration in dilated cardiomyopathy. Increased expression of Bcl-2 in cardiomyocytes indicates activation of an antiapoptotic response. These observations suggest that cardiomyocyte apoptosis is a clinically relevant and potentially modifiable pathophysiological phenomenon in severe heart failure.
authors.affiliation: Department of Anatomy, University of Turku, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Saraste
authors.forename: K
authors.initials: K
authors.lastname: Pulkki
authors.forename: M
authors.initials: M
authors.lastname: Kallajoki
authors.forename: P
authors.initials: P
authors.lastname: Heikkilä
authors.forename: P
authors.initials: P
authors.lastname: Laine
authors.forename: S
authors.initials: S
authors.lastname: Mattila
authors.forename: M S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: M
authors.initials: M
authors.lastname: Parvinen
authors.forename: L M
authors.initials: LM
authors.lastname: Voipio-Pulkki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002311:Cardiomyopathy, Dilated / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D006333:Heart Failure / Q000473:pathology* / Q000601:surgery; D016027:Heart Transplantation; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000473:pathology / Q000601:surgery; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2