title: Cardiomyocyte hypertrophy, oncosis, and autophagic vacuolization predict mortality in idiopathic dilated cardiomyopathy with advanced heart failure.
abstract: OBJECTIVE
  The aim of this study was to identify the remodeling parameters cardiomyocyte (CM) damage or death, hypertrophy, and fibrosis that may be linked to outcomes in patients with advanced heart failure (HF) in an effort to understand the pathogenic mechanisms of HF that may support newer therapeutic modalities.
  
  
  BACKGROUND
  There are controversial results on the influence of fibrosis, CM hypertrophy, and apoptosis on outcomes in patients with HF; other modalities of cell damage have been poorly investigated.
  
  
  METHODS
  In endomyocardial biopsy specimens from 100 patients with idiopathic dilated cardiomyopathy and advanced HF, CM diameter and the extent of fibrosis were determined by morphometry. The proportion of CMs with evidence of apoptosis, autophagic vacuolization (AuV), and oncosis was investigated by immunohistochemical methods and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling. Those parameters were correlated with mortality in 3 years of follow-up by univariate analysis and with multivariate models incorporating the clinical variables more relevant to the prediction of outcomes.
  
  
  RESULTS
  CM AuV occurred in 28 patients (0.013 ± 0.012%) and oncosis in 41 (0.109 ± 0.139%). Nineteen patients showed both markers. Apoptotic CM nuclei were observed in 3 patients. In univariate analysis, CM diameter and AuV, either alone or associated with oncosis, were predictors of mortality. In multivariate analysis, CM diameter (hazard ratio: 1.37; 95% confidence interval: 1.12 to 1.68; p = 0.002) and simultaneous presence in the same endomyocardial biopsy specimen of AuV and oncosis (hazard ratio: 2.82; 95% confidence interval: 1.12 to 7.13; p = 0.028) were independent predictors of mortality.
  
  
  CONCLUSIONS
  CM hypertrophy and AuV, especially in association with oncosis, are predictors of outcome in patients with idiopathic dilated cardiomyopathy and severe HF.
authors: Department of Pathology, University Hospital Favaloro Foundation, Buenos Aires, Argentina.
authors: Carlos A
authors: CA
authors: Vigliano
authors: Patricia M
authors: PM
authors: Cabeza Meckert
authors: Mirta
authors: M
authors: Diez
authors: Liliana E
authors: LE
authors: Favaloro
authors: Claudia
authors: C
authors: Cortés
authors: Lucía
authors: L
authors: Fazzi
authors: Roberto R
authors: RR
authors: Favaloro
authors: Rubén P
authors: RP
authors: Laguens
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000401:mortality / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D006333:Heart Failure / Q000150:complications / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000473:pathology*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012720:Severity of Illness Index; D020257:Ventricular Remodeling