title: Autophagic vacuoles in cardiomyocytes of dilated cardiomyopathy with initially decompensated heart failure predict improved prognosis.
abstract: Autophagy is a process of bulk protein degradation and organelle turnover, and is a current therapeutic target in several diseases. The present study aimed to clarify the significance of myocardial autophagy of patients with dilated cardiomyopathy (DCM). Left ventricular endomyocardial biopsy was performed in 250 consecutive patients with DCM (54.9±13.9 years; male, 79%), initially presenting with decompensated heart failure (HF). The association of these findings with HF mortality or recurrence was examined. Myofilament changes, which are apparent in the degenerated cardiomyocytes of DCM, were recognized in 164 patients (66%), and autophagic vacuoles in cardiomyocytes were identified in or near the area of myofilament changes in 86 patients (34%). Morphometrically, fibrosis (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.93 to 0.99) and mitochondrial abnormality (OR, 2.24; 95% CI, 1.23 to 4.08) were independently related with autophagic vacuoles. During the follow-up period of 4.9±3.9 y, 24 patients (10%) died, including 10 (4%) who died of HF, and 67 (27%) were readmitted for HF recurrence. Multivariate analysis identified a family history of DCM (hazard ratio [HR], 2.117; 95% CI, 1.199 to 3.738), hemoglobin level (HR, 0.845; 95% CI, 0.749 to 0.953), myofilament changes (HR, 13.525; 95% CI, 5.340 to 34.255), and autophagic vacuoles (HR, 0.214; 95% CI, 0.114 to 0.400) as independent predictors of death or readmission due to HF recurrence. In conclusion, autophagic vacuoles in cardiomyocytes are associated with a better HF prognosis in patients with DCM, suggesting autophagy may play a role in the prevention of myocardial degeneration.
authors.affiliation: a Department of Cardiovascular Medicine , Nippon Medical School , Tokyo , Japan.
authors.forename: Tsunenori
authors.initials: T
authors.lastname: Saito
authors.affiliation: a Department of Cardiovascular Medicine , Nippon Medical School , Tokyo , Japan.
authors.forename: Kuniya
authors.initials: K
authors.lastname: Asai
authors.affiliation: b Tokyo Electron Microscopy Laboratory , Chiba , Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sato
authors.affiliation: a Department of Cardiovascular Medicine , Nippon Medical School , Tokyo , Japan.
authors.forename: Meiso
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: c Division of Morphological and Biomolecular Research , Graduate School of Medicine, Nippon Medical School , Tokyo , Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Adachi
authors.affiliation: c Division of Morphological and Biomolecular Research , Graduate School of Medicine, Nippon Medical School , Tokyo , Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: a Department of Cardiovascular Medicine , Nippon Medical School , Tokyo , Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takano
authors.affiliation: a Department of Cardiovascular Medicine , Nippon Medical School , Tokyo , Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: a Department of Cardiovascular Medicine , Nippon Medical School , Tokyo , Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Shimizu
mesh_terms: D001343:Autophagy; D002311:Cardiomyopathy, Dilated / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000473:pathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000648:ultrastructure; D011379:Prognosis; D016896:Treatment Outcome; D014617:Vacuoles / Q000473:pathology* / Q000648:ultrastructure
keywords: Autophagy; dilated cardiomyopathy; electron microscopy; endomyocardial biopsy; heart failure; prognosis