Wolff- Parkinson-White Syndrome And Conduction Abnormalities Have Higher Prevalence In Patients With Mitochondrial Encephalomyopathy, Lactic Acidosis, And Stroke-like Episodes (MELAS) And Mutations Associated With MELAS

Background: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the most common mitochondrial disorders. Cardiovascular involvement has been reported in up to 30% of MELAS patients with varying clinical presentations from non-specific cardiogenic abnormalities to conduction abnormalities, cardiomyopathies, heart failure, fatal arrhythmias and cardiac death. Although conduction defects are a known complication, the frequency of Wolff-Parkinson-White (WPW) syndrome among MELAS patients and mutations associated with MELAS is uncertain, and their association with cardiomyopathy and treatment outcomes have rarely been reported. Methods: A retrospective chart review of fifty patients with MELAS genotypes from January 2007 to December 2022 was conducted at the Center for the Treatment of Pediatric Neurodegenerative Disease at UT Health Science Center Houston. Medical histories, electrocardiograms, echocardiograms, electrophysiology studies were reviewed and DNA samples from buccal epithelial cells, blood and hair were analyzed to determine mitochondrial mutation and total mutation burden. Results: Forty-three patients were included. Five of twenty patients with m.3242A>G MELAS (20 %), one of three patients m.4317A>G MELAS (33.3%) and two of twenty patients with m.3242A>G had electrocardiographic findings consistent with WPW. Other conduction abnormalities were noted in ten of 20 patients (50%) with MELAS and six out of twenty patients with m.3242A>G mutation (30%). Four patients required electrophysiology studies with ablation, one for inappropriate sinus tachycardia resistant to several medications, and three patients with WPW syndrome all of whom required repeat ablations. Conduction abnormalities were noted to have positive correlation with higher heteroplasmy levels (mean 35 % vs 51%, 95% CI, p=0.019). Six patients with MELAS had cardiomyopathy of varying severity which were all associated with conduction abnormalities, including two patients with WPW syndrome (p=0.014). Conclusion: The prevalence of WPW in patients with MELAS syndrome and the m.3242A>G variant appears much higher than in the normal population and may require multiple electrophysiology studies ablations to treat. Routine cardiology screening is recommended for early detection.