In adults with mitochondrial diseases, prediction models using genetic and cardiac assessments accurately estimated the risk of heart failure (C-index 0.91) and arrhythmic MACE (C-index 0.80).
Cohort (n=600)
Yes
What are the clinical and genetic predictors of heart failure and arrhythmic MACE in adults with mitochondrial diseases?
Genetic variant type and simple cardiac assessments can accurately predict the risk of heart failure and arrhythmic MACE in adults with mitochondrial diseases.
BACKGROUND Patients with mitochondrial diseases are at risk of heart failure (HF) and arrhythmic major adverse cardiac events (MACE). OBJECTIVES We developed prediction models to estimate the risk of HF and arrhythmic MACE in this population. METHODS We determined the incidence and searched for predictors of HF and arrhythmic MACE using Cox regression in 600 adult patients from a multicenter registry with genetically confirmed mitochondrial diseases. RESULTS Over a median follow-up time of 6.67 years, 29 patients (4.9%) reached the HF endpoint, including 19 hospitalizations for nonterminal HF, 2 cardiac transplantations, and 8 deaths from HF. Thirty others (5.1%) reached the arrhythmic MACE, including 21 with third-degree or type II second-degree atrioventricular blocks, 4 with sinus node dysfunction, and 5 sudden cardiac deaths. Predictors of HF were the m.3243A>G variant (HR: 4.3; 95% CI: 1.8-10.1), conduction defects (HR: 3.0; 95% CI: 1.3-6.9), left ventricular (LV) hypertrophy (HR: 2.6; 95% CI: 1.1-5.8), LV ejection fraction <50% (HR: 10.2; 95% CI: 4.6-22.3), and premature ventricular beats (HR: 4.1; 95% CI: 1.7-9.9). Independent predictors for arrhythmia were single, large-scale mtDNA deletions (HR: 4.3; 95% CI: 1.7-10.4), conduction defects (HR: 6.8; 95% CI: 3.0-15.4), and LV ejection fraction <50% (HR: 2.7; 95% CI: 1.1-7.1). C-indexes of the Cox regression models were 0.91 (95% CI: 0.88-0.95) and 0.80 (95% CI: 0.70-0.90) for the HF and arrhythmic MACE, respectively. CONCLUSIONS We developed the first prediction models for HF and arrhythmic MACE in patients with mitochondrial diseases using genetic variant type and simple cardiac assessments.
“Patients with mitochondrial diseases have a high risk of HF and arrhythmia-related major adverse cardiac events (MACE), which remains extremely challenging to estimate in the absence of specific prediction models. In this international multicenter study, we sought to analyze the frequency of arrhythmia-related and HF complications in a large cohort of patients with genetically confirmed mitochondrial diseases and to identify risk factors for the development of these two events to guide the implementation of specific diagnostic and therapeutic measures.”
Savvatis et al. (2022) conducted a cohort in Mitochondrial diseases (n=600). Clinical and genetic predictors (e.g., LVEF <50%, conduction defects, mtDNA variants) was evaluated on Heart failure (HF) and arrhythmic major adverse cardiac events (MACE). In adults with mitochondrial diseases, prediction models using genetic and cardiac assessments accurately estimated the risk of heart failure (C-index 0.91) and arrhythmic MACE (C-index 0.80).