An International Multicenter Cohort Study on ß-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. ß-Blockers decrease this risk, but studies comparing individual ß-blockers in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of ß-blocker in a large cohort of symptomatic children with CPVT. METHODS: From 2 international registries of patients with CPVT, RYR2 variant-carrying symptomatic children (defined as syncope or sudden cardiac arrest before ß-blocker initiation and age at start of ß-blocker therapy <18 years), treated with a ß-blocker were included. Cox regression analyses with time-dependent covariates for ß-blockers and potential confounders were used to assess the hazard ratio (HR). The primary outcome was the first occurrence of sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter-defibrillator shock, or syncope. The secondary outcome was the first occurrence of any of the primary outcomes except syncope. RESULTS: We included 329 patients (median age at diagnosis, 12 [interquartile range, 7-15] years, 35% females). Ninety-nine (30.1%) patients experienced the primary outcome and 74 (22.5%) experienced the secondary outcome during a median follow-up of 6.7 (interquartile range, 2.8-12.5) years. Two-hundred sixteen patients (66.0%) used a nonselective ß-blocker (predominantly nadolol [n=140] or propranolol [n=70]) and 111 (33.7%) used a ß1-selective ß-blocker (predominantly atenolol [n=51], metoprolol [n=33], or bisoprolol [n=19]) as initial ß-blocker. Baseline characteristics did not differ. The HRs for both the primary and secondary outcomes were higher for ß1-selective compared with nonselective ß-blockers (HR, 2.04 [95% CI, 1.31-3.17]; and HR, 1.99 [95% CI, 1.20-3.30], respectively). When assessed separately, the HR for the primary outcome was higher for atenolol (HR, 2.68 [95% CI, 1.44-4.99]), bisoprolol (HR, 3.24 [95% CI, 1.47-7.18]), and metoprolol (HR, 2.18 [95% CI, 1.08-4.40]) compared with nadolol, but did not differ from propranolol. The HR of the secondary outcome was only higher in atenolol compared with nadolol (HR, 2.68 [95% CI, 1.30-5.55]). CONCLUSIONS: ß1-selective ß-blockers were associated with a significantly higher risk for arrhythmic events in symptomatic children with CPVT compared with nonselective ß-blockers, specifically nadolol. Nadolol, or propranolol if nadolol is unavailable, should be the preferred ß-blocker for treating symptomatic children with CPVT.

Diagnostic accuracy of the 12-lead electrocardiogram in the first 48 hours of life for newborns of a parent with congenital long QT syndrome.

BACKGROUND: Long QT syndrome (LQTS) is an autosomal dominant disorder characterized by a prolonged QT interval. Electrocardiographic (ECG) screening in the first 48 hours of life may be misleading, even in newborns with a genotype-positive LQTS parent. OBJECTIVE: The purpose of this study was to determine the ECG's diagnostic accuracy in the first 48 hours of life for neonates born to a parent with LQTS. METHODS: We conducted a retrospective review of all neonates born at Mayo Clinic to a parent with ≥1 pathogenic variant in a LQTS-causative gene who had least 1 ECG in the first 48 hours and genetic test results were available. The sensitivity and specificity of the diagnostic ECG were calculated using Bazett's heart rate-corrected QT (QTc) thresholds of 440, 450, 460, and 470 ms. RESULTS: Overall, 74 newborns (36 females [49%]) were included (mean QTc interval on the first ECG 489 ± 54 ms; 50 [68%] LQTS genotype-positive). The mean QTc interval in the first 48 hours for neonates that ultimately were genotype-positive was greater (506 ± 52 ms) than that for genotype-negative neonates (455 ± 41 ms) (P = .0004). When using a recommended threshold QTc interval of ≥440 ms, 6 of 50 genotype-positive neonates (12%) were missed (underdiagnosed) and 17 of 24 genotype-negative neonates (71%) were overdiagnosed (sensitivity 88%; specificity 29%). CONCLUSION: The newborn ECG should not be used in isolation to make the diagnosis of LQTS since it will result in many misclassifications. Genetic testing must be initiated before discharge, and proper anticipatory guidance is vital while awaiting test results.

Left Cardiac Sympathetic Denervation Monotherapy in Patients With Congenital Long QT Syndrome.

BACKGROUND: Videoscopic left cardiac sympathetic denervation (LCSD) is an effective antifibrillatory, minimally invasive therapy for patients with potentially life-threatening arrhythmia syndromes like long QT syndrome (LQTS). Although initially used primarily for treatment intensification following documented LQTS-associated breakthrough cardiac events while on beta-blockers, LCSD as 1-time monotherapy for certain patients with LQTS requires further evaluation. We are presenting our early experience with LCSD monotherapy for carefully selected patients with LQTS. METHODS: Among the 1400 patients evaluated and treated for LQTS, a retrospective review was performed on the 204 patients with LQTS who underwent LCSD at our institution since 2005 to identify the patients where the LCSD served as stand-alone, monotherapy. Clinical data on symptomatic status before diagnosis, clinical, and genetic diagnosis, and breakthrough cardiac events after diagnosis were analyzed to determine efficacy of LCSD monotherapy. RESULT: Overall, 64 of 204 patients (31%) were treated with LCSD alone (37 [58%] female, mean QTc 466±30 ms, 16 [25%] patients were symptomatic before diagnosis with a mean age at diagnosis 17.3±11.8 years, 5 had [8%] ≥1 breakthrough cardiac event after diagnosis, and mean age at LCSD was 21.1±11.4 years). The primary motivation for LCSD monotherapy was an unacceptable quality of life stemming from beta-blocker related side effects (ie, beta-blocker intolerance) in 56/64 patients (88%). The underlying LQTS genotype was LQT1 in 36 (56%) and LQT2 in 20 (31%). There were no significant LCSD-related surgical complications. With a mean follow-up of 2.7±2.4 years so far, only 3 patients have experienced a nonlethal, post-LCSD breakthrough cardiac event in 180 patient-years. CONCLUSIONS: LCSD may be a safe and effective stand-alone therapy for select patients who do not tolerate beta-blockers. However, LCSD is not curative and patient selection will be critical when potentially considering LCSD as monotherapy.