Cardiac Prognosis in Mitochondrial Diseases

Study Questions:

What is the long-term cardiac prognosis of adults with mitochondrial diseases?


The study cohort included 260 consecutive patients with genetically proven mitochondrial diseases including 109 with mitochondrial DNA (mtDNA) single large-scale deletions, 64 with the m.3243A.G mutation in MT-TL1, 51 with other mtDNA point mutations, and 36 patients with nuclear gene mutations. This was a retrospective study where the authors performed single and multiple variable analyses in search of predictors of major adverse cardiac events (MACE)—defined as sudden death, death due to heart failure (HF), resuscitated cardiac arrest, third-degree atrioventricular block, sinus node dysfunction, cardiac transplantation, or hospitalization for management of HF. They used multivariable analyses to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for these predictors.


Sixty-percent of the study cohort was women, all participants were aged ≥18 years, and median age was 43 years (interquartile range [IQR], 31–54 years). The median follow-up period was 7 years (IQR, 3.6-11.7 years). The study authors found that 10% of the patients (n = 27) suffered a MACE. The mean age at the time of MACE during follow-up was 50 years (IQR, 35–61 years). The highest incidence of MACE was observed in patients with single large-scale mtDNA deletions or m.3243A.G mutations. The authors found that intraventricular conduction block (HR, 16.9; 95% CI, 7.2–39.4), diabetes (HR, 7.0; 95% CI, 2.9–16.7), premature ventricular complexes (HR, 3.6; 95% CI, 1.4–9.2), and left ventricular (LV) hypertrophy (HR, 2.5; 95% CI, 1.1–5.8) were independent predictors of MACE. The incidences of MACE in patients with zero, one, and two or more risk factors, were 1.7%, 15%, and 42%, respectively.


The authors concluded that patients with mitochondrial diseases are at high risk of MACE, independently predicted by intraventricular conduction block, diabetes, ventricular premature beats, and LV hypertrophy.


The findings of this study are important because these risk markers can be used to generate specific therapy for mitochondrial diseases rather than the empirical approach that is currently utilized. The salient findings in these patients include: (a) a 30% prevalence of cardiac involvement; (b) a 10% incidence of MACE over a median 7-year follow-up; and (c) independent predictors of MACE include intraventricular conduction defects, diabetes, premature ventricular contractions, and LV hypertrophy. Prospective studies are now needed to confirm these findings.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant

Keywords: Atrioventricular Block, DNA, Mitochondrial, Death, Sudden, Diabetes Mellitus, Heart Arrest, Heart Failure, Heart Transplantation, Hypertrophy, Left Ventricular, Mitochondrial Diseases, Prognosis, Risk Factors, Ventricular Premature Complexes

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