title: MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.
abstract: Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada.
authors.forename: Ying-Han R
authors.initials: YR
authors.lastname: Hsu
authors.affiliation: Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, 8440 112 Street NW, Edmonton, AB, T6G 2B7, Canada.
authors.forename: Haran
authors.initials: H
authors.lastname: Yogasundaram
authors.affiliation: Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, 8440 112 Street NW, Edmonton, AB, T6G 2B7, Canada.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Parajuli
authors.affiliation: Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, 8440 112 Street NW, Edmonton, AB, T6G 2B7, Canada.
authors.forename: Lucas
authors.initials: L
authors.lastname: Valtuille
authors.affiliation: Department of Laboratory Medicine and Pathology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada.
authors.forename: Consolato
authors.initials: C
authors.lastname: Sergi
authors.affiliation: Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, 8440 112 Street NW, Edmonton, AB, T6G 2B7, Canada. gavin.oudit@ualberta.ca.
authors.forename: Gavin Y
authors.initials: GY
authors.lastname: Oudit
mesh_terms: D009202:Cardiomyopathies / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D017241:MELAS Syndrome / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D008660:Metabolism; D008928:Mitochondria / Q000378:metabolism*
keywords: Cardiomyopathy; HF; MELAS syndrome; Mitochondria