This international multidisciplinary document is intended to guide electrophysiologists, cardiologists, other clinicians, and health care professionals in caring for patients with arrhythmic... Show moreThis international multidisciplinary document is intended to guide electrophysiologists, cardiologists, other clinicians, and health care professionals in caring for patients with arrhythmic complications of neuromuscular disorders (NMDs). The document presents an overview of arrhythmias in NMDs followed by detailed sections on specific disorders: Duchenne muscular dystrophy, Becker muscular dystrophy, and limb-girdle muscular dystrophy type 2; myotonic dystrophy type 1 and type 2; Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy type 1B; facioscapulohumeral muscular dystrophy; and mitochondrial myopathies, including Friedreich ataxia and Kearns-Sayre syndrome, with an emphasis on managing arrhythmic cardiac manifestations. Endof-life management of arrhythmias in patients with NMDs is also covered. The document sections were drafted by the writing committee members according to their area of expertise. The recommendations represent the consensus opinion of the expert writing group, graded by class of recommendation and level of evidence utilizing defined criteria. The recommendations were made available for public comment; the document underwent review by the Heart Rhythm Society Scientific and Clinical Documents Committee and external review and endorsement by the partner and collaborating societies. Changes were incorporated based on these reviews. By using a breadth of accumulated available evidence, the document is designed to provide practical and actionable clinical information and recommendations for the diagnosis and management of arrhythmias and thus improve the care of patients with NMDs. Show less
IMPORTANCE Corticosteroidal anti-inflammatory drugs are widely prescribed but long-term use shows adverse effects that detract from patient quality of life.OBJECTIVE To determine if vamorolone, a... Show moreIMPORTANCE Corticosteroidal anti-inflammatory drugs are widely prescribed but long-term use shows adverse effects that detract from patient quality of life.OBJECTIVE To determine if vamorolone, a structurally unique dissociative steroidal anti-inflammatory drug, is able to retain efficacy while reducing safety concerns with use in Duchenne muscular dystrophy (DMD).DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo- and prednisone-controlled 24-week clinical trial, conducted from June 29, 2018, to February 24, 2021, with 24 weeks of follow-up. This was a multicenter study (33 referral centers in 11 countries) and included boys 4 to younger than 7 years of age with genetically confirmed DMD not previously treated with corticosteroids.INTERVENTIONS The study included 4 groups: placebo; prednisone, 0.75 mg/kg per day; vamorolone, 2 mg/kg per day; and vamorolone, 6 mg/kg per day.MAIN OUTCOMES AND MEASURES Study outcomes monitored (1) efficacy, which included motor outcomes (primary: time to stand from supine velocity in the vamorolone, 6 mg/kg per day, group vs placebo; secondary: time to stand from supine velocity [vamorolone, 2 mg/kg per day], 6-minute walk distance, time to run/walk 10 m [vamorolone, 2 and 6 mg/kg per day]; exploratory: NorthStar Ambulatory Assessment, time to dimb 4 stairs) and (2) safety, which included growth, bone biomarkers, and a corticotropin (ACTH)-challenge test.RESULTS Among the 133 boys with DMD enrolled in the study (mean [SD] age, 5.4 [0.9] years), 121were randomly assigned to treatment groups, and 114 completed the 24-week treatment period. The trial met the primary end point for change from baseline to week 24 time to stand velocity for vamorolone, 6 mg/kg per day (least-squares mean [SE] velocity. 0.05 [0.01] m/s vs placebo -0.01 [0.01] m/s; 95% CI, 0.02-0.10; P = .002) and the first 4 sequential secondary end points: time to stand velocity, vamorolone, 2 mg/kg per day, vs placebo; 6-minute walk test, vamorolone, 6 mg/kg per day, vs placebo; 6-minute walk test. vamorolone, 2 mg/kg per day, vs placebo; and time to run/walk 10 m velocity, vamorolone, 6 mg/kg per day, vs placebo. Height percentile declined in prednisone-treated (not vamorolone-treated) participants (change from baseline [SD]: prednisone, -1.88 [8.81] percentile vs vamorolone, 6 mg/kg per day, +3.86 [6.16] percentile; P = .02). Bone turnover markers declined with prednisone but not with vamorolone. Boys with DMD at baseline showed low ACTH-stimulated cortisol and high incidence of adrenal insufficiency. All 3 treatment groups led to increased adrenal insufficiency.CONCLUSIONS AND RELEVANCE in this pivotal randomized clinical trial, vamorolone was shown to be effective and safe in the treatment of boys with DMD over a 24-week treatment period. Vamorolone may be a safer alternative than prednisone in this disease, in which long-term corticosteroid use is the standard of care. Show less
