Cardiac Involvement and Long-Term Prognosis In Pediatric Mitochondrial Disease Patients

Objective: To describe the cardiac involvement in pediatric mitochondrial disease patients, and to investigate cardiac risk factors related to the long-term prognosis of these patients. Methods: We retrospectively reviewed the data from pediatric patients genetically diagnosed mitochondrial disease at Beijing Children’s hospital between January 1, 2012 and December 31, 2021. Results: A total of 381 patients were included with a confirmed genetic diagnosis, including with 136 patients (36%) nuclear gene mutations, 235 patients (62%) with mitochondrial DNA (mtDNA) point mutations and 10 patients (2%) with mtDNA single large-scale deletions. Cardiac involvements were observed in 102 patients (27%), including 48 patients (12%) had abnormal cardiac symptoms or signs, 46 patients (12%) had echocardiography abnormalities and 48 patients (47%) had electrocardiogram abnormalities. Over a median follow-up of 2.75 years (IQS: 1.02-4.18), 20 patients had developed major adverse cardiac events (MACEs) and 72 (19%) patients had dead. All-cause mortality shown no significant difference between children with or without cardiac involvement (23.5% VS 17%). By multivariable analysis, age of onset≤1 year old (HR = 2.0; 95% CI: 1.2–3.4), encephalopathy (HR = 1.8; 95% CI: 1.1–3.2), cardiac arrest (HR = 7.96; 95% CI: 2.1–39.2) and heart failure (HR=3.6 ; 95% CI: 1.7–7.6) were independent predictors of all-cause mortality. Conclusion: Cardiac involvements were common in pediatric mitochondrial disease patients (27%). Cardiac arrest, heart failure, age of onset≤1 year old and encephalopathy were independent predictors of all-cause mortality.