IMPORTANCE Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal genetic arrhythmia syndrome characterized by polymorphic ventricular tachycardia with physical or emotional stress, for which current therapy with β-blockers is incompletely effective. Flecainide acetate directly suppresses sarcoplasmic reticulum calcium release—the cellular mechanism responsible for triggering ventricular arrhythmias in CPVT—but has never been assessed prospectively. OBJECTIVE To determine whether flecainide dosed to therapeutic levels and added to β-blocker therapy is superior to β-blocker therapy alone for the prevention of exercise-induced arrhythmias in CPVT. DESIGN, SETTING, AND PARTICIPANTS This investigator-initiated, multicenter, single-blind, placebo-controlled crossover clinical trial was conducted from December 19, 2011, through December 29, 2015, with a midtrial protocol change at 10 US sites. Patients with a clinical diagnosis of CPVT and an implantable cardioverter-defibrillator underwent a baseline exercise test while receiving maximally tolerated β-blocker therapy that was continued throughout the trial. Patients were then randomized to treatment A (flecainide or placebo) for 3 months, followed by exercise testing. After a 1-week washout period, patients crossed over to treatment B (placebo or flecainide) for 3 months, followed by exercise testing. INTERVENTIONS Patients received oral flecainide or placebo twice daily, with the dosage guided by trough serum levels. MAIN OUTCOMES AND MEASURES The primary end point of ventricular arrhythmias during exercise was compared between the flecainide and placebo arms. Exercise tests were scored on an ordinal scale of worst ventricular arrhythmia observed (0 indicates no ectopy; 1, isolated premature ventricular beats; 2, bigeminy; 3, couplets; and 4, nonsustained ventricular tachycardia). RESULTS Of 14 patients (7 males and 7 females; median age, 16 years [interquartile range, 15.0–22.5 years]) randomized, 13 completed the study. The median baseline exercise test score was 3.0 (range, 0–4), with no difference noted between the baseline and placebo (median, 2.5; range, 0–4) exercise scores. The median ventricular arrhythmia score during exercise was significantly reduced by flecainide (0 [range, 0–2] vs 2.5 [range, 0–4] for placebo; P < .01), with complete suppression observed in 11 of 13 patients (85%). Overall and serious adverse events did not differ between the flecainide and placebo arms. CONCLUSIONS AND RELEVANCE In this randomized clinical trial of patients with CPVT, flecainide plus β-blocker significantly reduced ventricular ectopy during exercise compared with placebo plus β-blocker and β-blocker alone. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01117454

Objectives To measure the health-related quality of life (HRQOL) and functional status of children with cardiomyopathy and to determine whether they are correlated with sociodemographics, cardiac status, and clinical outcomes. Study design Parents of children in the Pediatric Cardiomyopathy Registry completed the Child Health Questionnaire (CHQ; age ≥5 years) and Functional Status II (Revised) (age ≤18 years) instruments. Linear and Cox regressions were used to examine hypothesized associations with HRQOL. Results The 355 children evaluated at ≥5 years (median 8.6 years) had lower functioning (CHQ Physical and Psychosocial Summary Scores 41.7 ± 14.4 and 47.8 ± 10.7) than that of healthy historical controls. The most extreme CHQ domain score, Parental Impact-Emotional, was one SD below normal. Younger age at diagnosis and smaller left ventricular end-diastolic dimension z score were associated independently with better physical functioning in children with dilated cardiomyopathy. Greater income/education correlated with better psychosocial functioning in children with hypertrophic and mixed/other types of cardiomyopathy. In the age ≥5 year cohort, lower scores on both instruments predicted earlier death/transplant and listing for transplant in children with dilated and mixed/other types of cardiomyopathy (P < .001). Across all ages (n = 565), the Functional Status II (Revised) total score was 87.1 ± 16.4, and a lower score was associated with earlier death/transplant for all cardiomyopathies. Conclusions HRQOL and functional status in children with cardiomyopathy is on average impaired relative to healthy children. These impairments are associated with older age at diagnosis, lower socioeconomic status, left ventricular size, and increased risk for death and transplant. Identification of families at risk for functional impairment allows for provision of specialized services early in the course of disease. Trial registration ClinicalTrials.gov: NCT00005391.

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Aims Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by exercise-induced ventricular arrhythmias, sudden death, and sinus bradycardia. Elevating supraventricular rates with pacing or atropine protects against catecholaminergic ventricular arrhythmias in a CPVT mouse model. We tested the hypothesis that increasing sinus heart rate (HR) with atropine prevents exercise-induced ventricular arrhythmias in CPVT patients. Methods and results We performed a prospective open-label trial of atropine prior to exercise in CPVT patients (clinicaltrials.gov NCT02927223). Subjects performed a baseline standard Bruce treadmill test on their usual medical regimen. After a 2-h recovery period, subjects performed a second exercise test after parasympathetic block with atropine (0.04 mg/kg intravenous). The primary outcome measure was the total number of ventricular ectopic beats during exercise. All six subjects (5 men, 22–57 years old) completed the study with no adverse events. Atropine increased resting sinus rate from median 52 b.p.m. (range 52–64) to 98 b.p.m. (84–119), P = 0.02. Peak HRs (149 b.p.m., range 136–181 vs. 149 b.p.m., range 127–182, P = 0.46) and exercise duration (612 s, range 544–733 vs. 584 s, range 543–742, P = 0.22) were not statistically different. All subjects had ventricular ectopy during the baseline exercise test. Atropine pre-treatment significantly decreased the median number of ventricular ectopic beats from 46 (6–192) to 0 (0–29), P = 0.026; ventricular ectopy was completely eliminated in 4/6 subjects. Conclusion Elevating sinus rates with atropine reduces or eliminates exercise-induced ventricular ectopy in patients with CPVT. Increasing supraventricular rates may represent a novel therapeutic strategy in CPVT.

Background Children with Down syndrome (DS) have a high risk of cardiac disease that may prompt consideration for heart transplantation (HTx). However, transplantation in patients with DS is rarely reported. This project aimed to collect and describe waitlist and post– HTx outcomes in children with DS. Methods and Results This is a retrospective case series of children with DS listed for HTx. Pediatric HTx centers were identified by their participation in 2 international registries with centers reporting HTx in a patient with DS providing detailed demographic, medical, surgical, and posttransplant outcome data for analysis. A total of 26 patients with DS were listed for HTx from 1992 to 2020 (median age, 8.5 years; 46% male). High‐risk or failed repair of congenital heart disease was the most common indication for transplant (N=18, 69%). A total of 23 (88%) patients survived to transplant. All transplanted patients survived to hospital discharge with a median posttransplant length of stay of 22 days. At a median posttransplant follow‐up of 2.8 years, 20 (87%) patients were alive, 2 (9%) developed posttransplant lymphoproliferative disorder, and 8 (35%) were hospitalized for infection within the first year. Waitlist and posttransplant outcomes were similar in patients with and without DS ( P =non‐significant for all). Conclusions Waitlist and post‐HTx outcomes in children with DS selected for transplant listing are comparable to pediatric HTx recipients overall. Given acceptable outcomes, the presence of DS alone should not be considered an absolute contraindication to HTx.