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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., Competing Interests: Funding Support and Author Disclosures This study was funded by grants from the Association Française contre les Myopathies (French Alliance against Myopathies), which was not involved in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review or approval of the manuscript; nor in the decision to submit the manuscript for publication. Dr Pitceathly is supported by a Medical Research Council (United Kingdom) Clinician Scientist Fellowship (MR/S002065/1). Drs Pitceathly and Hanna receive funding from a Medical Research Council (United Kingdom) strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) (MR/S005021/1). Dr Lopes is supported by a Medical Research Council (United Kingdom) clinical academic partnership (CARP) award. Dr Quinlivan was funded by National Institute for Health and Care Research Biomedical Research Centre, University College Hospitals Foundation Trust. The University College London Hospitals/University College London Queen Square Institute of Neurology sequencing facility receives a proportion of funding from the Department of Health's National Institute for Health and Care Research Biomedical Research Centre’s funding scheme. The clinical and diagnostic “Rare Mitochondrial Disorders” Service in London is funded by the U.K. NHS Highly Specialised Commissioners. Dr Elliott has received consultancy fees from Pfizer, Sanofi, Sarepta, DinaQor, Freeline, Novo Nordisk, and Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Following the 2017 approval of a first spinal muscular atrophy (SMA) treatment by the European Medicines Agency, SMA Europe launched a Europe-wide survey with the goal of understanding patients' treatment expectations, realities of daily living and access to clinical trials and therapy, and how this varied according to parameters such as age and disease severity. A response rate of 31% yielded 1474 completed surveys from 26 European countries. In line with findings from a 2015 SMA Europe-led survey, participants considered stabilization of their condition to be progress. Notably, responses indicated that the current classification of SMA at diagnosis by 'type' often does not reflect current mobility level. Large gaps in treatment access were identified that varied in particular between age and disease severity groups, yet there was high interest in clinical trial participation. In addition, alternative treatment options, including combination therapies, are now expectations. These perspectives should be central considerations through the research and development processes of new SMA therapies, through data generation and discussions on access to therapies. Results from this survey indicate that collaboration between stakeholders is essential to the foundation upon which innovative approaches for SMA treatments and access can be explored., Competing Interests: Declaration of Competing Interest N.G. is a volunteer for SMA Europe and SMA Schweiz, mother of two children, one living with SMA, and advisor and lecturer for Biogen, Novartis, Novartis Gene Therapies (AveXis) and Roche. E.S. is a volunteer for SMA Europe, Initiative SMA and DGM, and mother of two grown up children, one living with SMA. C.S., L.K. and A.M. are paid staff at AFM Téléthon. M.-C.O. is a volunteer board member for SMA Europe, AFM Téléthon, and GENETHON, mother of twins, one living with SMA, and advisor for Biogen, Novartis and Novartis Gene Therapies (AveXis). M.dL. is a volunteer for SMA Europe and FundAME, mother of two children living with SMA, and advisor for Biogen, Novartis, Novartis Gene Therapies (AveXis), and Roche., (Copyright © 2021 Elsevier B.V. All rights reserved.)