Cardiac Outcomes in Adults With Mitochondrial Diseases

• DOI: 10.1016/j.jacc.2022.08.716
• Publication Date: 2022-10-03T17:21:54Z
• Authors: Konstantinos Savv...; Christoffer Rasmu...; Lori Klouvi; Anca Florian; Mehjabin Rahman; Anthony Béhin; Abdallah Fayssoil; Marion Masingue; Tanya Stojkovic; Henri Marc Bécane; Nawal Berber; Fanny Mochel; Denis Duboc; Bertrand Fontaine; Bjørg Krett; Caroline Stalens; Julie Lejeune; Robert D.S. Pitce...; Luis Lopes; Malika Saadi; Thomas Gossios; Vincent Procaccio; Marco Spinazzi; Céline Tard; Pascal De Groote; Claire-Marie Dhae...; Claire Douillard; Andoni Echaniz-La...; Ros Quinlivan; Michael G. Hanna; Ali Yilmaz; John Vissing; Pascal Laforêt; Perry Elliott; Karim Wahbi
• Keywords: INVOLVEMENT; Adult; Cardiac & Cardiovascular Systems; KEARNS-SAYRE SYNDROME; Mitochondrial Diseases; DNA MUTATIONS; [SDV]Life Sciences [q-bio]; 610; heart failure; sudden death; AMERICAN-COLLEGE; DNA, Mitochondrial; single large-scale deletions; Ventricular Function, Left; 03 medical and health sciences; 0302 clinical medicine; Risk Factors; Humans; ASSOCIATION TASK-FORCE; COMMITTEE; m3243A>G; conduction disease; Heart Failure; mitochondrial diseases; Science & Technology; CARDIOMYOPATHY; ABNORMALITIES; m3243A > G; Heart; Stroke Volume; Prognosis; PREVALENCE; 3. Good health; CONDUCTION; Cardiovascular System & Cardiology; Hypertrophy, Left Ventricular; Life Sciences & Biomedicine

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.