Abstract
Although neuromuscular clinical features often dominate the clinical presentation of mitochondrial disease due to the m.3243A>G mitochondrial DNA (mtDNA) mutation, many patients develop cardiac failure, which is often overlooked until it reaches an advanced stage. We set out to determine whether cardiac complications are sufficiently common to warrant prospective screening in all mutation carriers. Routine clinical echocardiography and 3 Tesla cardiac MRI were performed on ten m.3243A>G mutation carriers and compared to age and gender matched controls, with contemporaneous quadriceps muscle biopsies to measure respiratory chain activity and mtDNA mutation levels. Despite normal echocardiography, all ten m.3243A>G mutation carriers had evidence of abnormal cardiac function on MRI. The degree of cardiac dysfunction correlated with the percentage level of mutant mtDNA in skeletal muscle. Sub-clinical cardiac dysfunction was a universal finding in this study, adding weight to the importance of screening for cardiac complications in patients with m.3243A>G. The early detection of cardiac dysfunction with MRI opens up opportunities to prevent heart failure in these patients through early intervention.
Highlights
Neurological features usually dominate the clinical presentation of patients harbouring the m.3243A>G mitochondrial DNA mutation; with migraine, encephalopathy, seizures, stroke-like episodes, deafness, ophthalmoplegia and myopathy all being common
The major findings were: (1) concentric left ventricular hypertrophy in the absence of systemic hypertension; and (2) a re-orientation of myocardial strains with reduced longitudinal shortening and increased torsion. These findings indicate that sub-clinical cardiomyopathy is common in m.3243A>G patients, and may be a universal finding
Given previous reports of progressive cardiac hypertrophy leading to irreversible dilated cardiomyopathy in m.3243A>G patients [7], our observations re-enforce the importance of cardiac monitoring in all m.3243A>G mutation carriers
Summary
Neurological features usually dominate the clinical presentation of patients harbouring the m.3243A>G mitochondrial DNA (mtDNA) mutation; with migraine, encephalopathy, seizures, stroke-like episodes, deafness, ophthalmoplegia and myopathy all being common. ⇑ Corresponding author at: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK. Using relatively insensitive 2D-echocardiography, left-ventricular hypertrophy was been detected in 56% of cases [2], raising the possibility that cardiac dysfunction is major feature of the disorder potentially amenable to early treatment to prevent cardiac failure [5]. To address this issue, we used cardiac magnetic resonance imaging (MRI) to determine the prevalence of cardiac dysfunction in m.3243A>G mutation carriers, with contemporaneous genetic and biochemical studies on skeletal muscle to elucidate the mechanism
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