Cardiac Outcomes in Adults With Mitochondrial Diseases

Area of Science:

• Cardiology
• Genetics
• Mitochondrial Diseases

Background:

• Mitochondrial diseases significantly increase the risk of heart failure (HF) and major adverse cardiac events (MACE), specifically arrhythmias.
• Early identification and risk stratification are crucial for managing cardiac complications in these patients.

Purpose of the Study:

• To develop and validate prediction models for heart failure (HF) and arrhythmic major adverse cardiac events (MACE) in adult patients with genetically confirmed mitochondrial diseases.
• To identify key predictors of HF and arrhythmic MACE within this specific patient population.

Main Methods:

• A multicenter registry of 600 adult patients with genetically confirmed mitochondrial diseases was utilized.
• Cox regression analysis was employed to determine the incidence and predictors of HF and arrhythmic MACE over a median follow-up of 6.67 years.

Main Results:

• The study identified specific genetic variants (m.3243A>G, single large-scale mtDNA deletions) and cardiac assessments (conduction defects, left ventricular hypertrophy, LV ejection fraction <50%, premature ventricular beats) as significant predictors.
• Incidence rates were 4.9% for HF and 5.1% for arrhythmic MACE.
• Developed Cox regression models demonstrated high predictive accuracy (C-indexes of 0.91 for HF and 0.80 for arrhythmic MACE).

Conclusions:

• The first prediction models for HF and arrhythmic MACE in mitochondrial disease patients have been successfully developed.
• These models effectively integrate genetic variant type and simple cardiac assessments for risk prediction.
• The findings provide valuable tools for clinical management and prognostication in patients with mitochondrial diseases.