Systematic review and meta-analysis of cardiac involvement in mitochondrial myopathy

Objective Our goal was to perform a systematic review of the literature to demonstrate the prevalence of cardiac abnormalities identified using cardiac investigations in patients with mitochondrial myopathy (MM). Methods This systematic review surveys the available evidence for cardiac investigations in MM from a total of 21 studies including 825 participants. Data were stratified by genetic mutation and clinical syndrome. Results We identified echocardiogram and ECG as the principal screening modalities that identify cardiac structural (29%) and conduction abnormalities (39%) in various MM syndromes. ECG abnormalities were more prevalent in patients with m.3243A>G mutations than other gene defects, and patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) had a higher prevalence of ECG abnormalities than patients with other clinical syndromes. Echocardiogram abnormalities were significantly more prevalent in patients with m.3243A>G or m.8344A>G mutations compared with other genetic mutations. Similarly, MELAS and MERRF had a higher prevalence compared with other syndromes. We observed a descriptive finding of an increased prevalence of ECG abnormalities in pediatric patients compared with adults. Conclusions This analysis supports the presence of a more severe cardiac phenotype in MELAS and myoclonic epilepsy with ragged red fibres syndromes and with their commonly associated genetic mutations (m.3243A>G and m.8344A>G). This provides the first evidence basis on which to provide more intensive cardiac screening for patients with certain clinical syndromes and genetic mutations. However, the data are based on a small number of studies. We recommend further studies of natural history, therapeutic response, pediatric participants, and cardiac MRI as areas for future investigation.