Impact of Autophagy on Prognosis of Patients With Dilated Cardiomyopathy

Abstract

BackgroundAutophagy is a cellular process that degrades a cell’s own cytoplasmic components for energy provision and to maintain a proper intracellular environment. Left ventricular reverse remodeling (LVRR) promises a better prognosis for patients with dilated cardiomyopathy (DCM). ObjectivesThe authors tested the hypothesis that autophagy is involved in LVRR and has prognostic value in the human failing heart. MethodsUsing left ventricular endomyocardial biopsy specimens from 42 patients with DCM (21 LVRR-positive and 21 LVRR-negative) and 7 patients with normal cardiac function (control), the authors performed immunohistochemistry and immunofluorescent labeling of LC3 and cathepsin D and electron microscopic observation in addition to general morphometry under light microscopy. ResultsThe clinical characteristics of LVRR-positive patients were similar to those of the LVRR-negative patients, except for pulmonary artery pressure and left atrial dimension. Morphometry under light microscopy did not differ among specimens from DCM patients, regardless of their LVRR status. Electron microscopy revealed that autophagic vacuoles (autophagosomes and autolysosomes) and lysosomes were abundant within cardiomyocytes from DCM patients. Moreover, cardiomyocytes from LVRR-positive patients contained significantly more autophagic vacuoles with higher autolysosome ratios and cathepsin D expression levels than cardiomyocytes from LVRR-negative patients. Logistic regression analysis adjusted for age showed that increases in autophagic vacuole number and cathepsin D expression were predictive of LVRR. DCM patients who achieved LVRR experienced fewer cardiovascular events during the follow-up period. ConclusionsThe authors show that autophagy is a useful marker predictive of LVRR in DCM patients. This provides novel pathologic insight into a strategy for treating the failing DCM heart.