Cardiac Involvement in Patients with MELAS-Related mtDNA 3243A>G Variant

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare disease with variable clinical manifestations. MELAS is most often caused by the human mitochondrial DNA (mtDNA) m.3243A>G variant. We describe cardiac magnetic resonance (CMR) imaging findings and clinical features of 22 subjects with the m.3243A>G mutation and endeavored to discover the role of CMR in MELAS cardiomyopathy diagnostics. The clinical symptoms, ECG findings, and laboratory tests were retrospectively collected from the electronic medical record. Ten subjects (46%) had cardiac symptoms, and eighteen subjects (82%) had some clinical symptoms or signs of MELAS. Seventeen subjects (77%) showed cardiac findings compatible with MELAS. An ECG showed a short PR interval in six subjects (27%). Two patients had a first-degree atrioventricular block. Repolarization changes in the ECG were observed in thirteen subjects (59%), whereas left ventricular hypertrophy voltage criteria were only observed in one subject. Patients with ECG abnormalities had a strong link between proBNP value and cardiac tissue composition (T1 relaxation, p < 0.02) and showed decreased CMR-based strain (p < 0.025). The CMR findings are heterogeneous in subjects with m.3243A>G. Cardiac MELAS may include left ventricular hypertrophy, which mimics sarcomericcardiomyopathy but maypredispose individuals to severe heart failure episodes triggered by acute critical situations. CMR may be used to clarify ECG findings. This study indicates that the genetic testing of MELAS should be considered in new cases of HCM or sudden heart failure phenotypes of unknown etiology.