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Heart Failure Reviews
Published in: Heart Failure Reviews 1/2016

01-01-2016

MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis

Authors: Ying-Han R. Hsu, Haran Yogasundaram, Nirmal Parajuli, Lucas Valtuille, Consolato Sergi, Gavin Y. Oudit

Published in: Heart Failure Reviews | Issue 1/2016

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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.
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Metadata
Title
MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis
Authors
Ying-Han R. Hsu
Haran Yogasundaram
Nirmal Parajuli
Lucas Valtuille
Consolato Sergi
Gavin Y. Oudit
Publication date
01-01-2016
Publisher
Springer US
Published in
Heart Failure Reviews / Issue 1/2016
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI
https://doi.org/10.1007/s10741-015-9524-5

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