Cardiac Outcomes in Adults With Mitochondrial Diseases

• Published in: Journal of the American College of Cardiology Vol. 80; no. 15; pp. 1421 - 1430
• Main Authors: Savvatis, Konstantinos, Vissing, Christoffer Rasmus, Klouvi, Lori, Florian, Anca, Rahman, Mehjabin, Béhin, Anthony, Fayssoil, Abdallah, Masingue, Marion, Stojkovic, Tanya, Bécane, Henri Marc, Berber, Nawal, Mochel, Fanny, Duboc, Denis, Fontaine, Bertrand, Krett, Bjørg, Stalens, Caroline, Lejeune, Julie, Pitceathly, Robert D.S., Lopes, Luis, Saadi, Malika, Gossios, Thomas, Procaccio, Vincent, Spinazzi, Marco, Tard, Céline, De Groote, Pascal, Dhaenens, Claire-Marie, Douillard, Claire, Echaniz-Laguna, Andoni, Quinlivan, Ros, Hanna, Michael G., Yilmaz, Ali, Vissing, John, Laforêt, Pascal, Elliott, Perry, Wahbi, Karim
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.10.2022; Elsevier
• Subjects: Adult; Cardiovascular; conduction disease; DNA, Mitochondrial - genetics; Heart; heart failure; Heart Failure - epidemiology; Humans; Hypertrophy, Left Ventricular; Life Sciences; m3243A>G; mitochondrial diseases; Mitochondrial Diseases - complications; Mitochondrial Diseases - epidemiology; Mitochondrial Diseases - genetics; Prognosis; Risk Factors; single large-scale deletions; Stroke Volume; sudden death; Ventricular Function, Left; heart failure; sudden death; EF; mitochondrial diseases; MACE; single large-scale deletions; m3243A>G; LV; conduction disease; HF; ejection fraction; left ventricle; major adverse cardiac event(s)
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2022.08.716

Patients with mitochondrial diseases are at risk of heart failure (HF) and arrhythmic major adverse cardiac events (MACE). We developed prediction models to estimate the risk of HF and arrhythmic MACE in this population. 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. 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. We developed the first prediction models for HF and arrhythmic MACE in patients with mitochondrial diseases using genetic variant type and simple cardiac assessments. [Display omitted]