BackgroundAn elegant bedside provocation test has been shown to aid the diagnosis of long‐QT syndrome (LQTS) in a retrospective cohort by evaluation of QT intervals and T‐wave morphology changes... Show moreBackgroundAn elegant bedside provocation test has been shown to aid the diagnosis of long‐QT syndrome (LQTS) in a retrospective cohort by evaluation of QT intervals and T‐wave morphology changes resulting from the brief tachycardia provoked by standing. We aimed to prospectively determine the potential diagnostic value of the standing test for LQTS.Methods and ResultsIn adults suspected for LQTS who had a standing test, the QT interval was assessed manually and automated. In addition, T‐wave morphology changes were determined. A total of 167 controls and 131 genetically confirmed patients with LQTS were included. A prolonged heart rate–corrected QT interval (QTc) (men ≥430 ms, women ≥450 ms) at baseline before standing yielded a sensitivity of 61% (95% CI, 47–74) in men and 54% (95% CI, 42–66) in women, with a specificity of 90% (95% CI, 80–96) and 89% (95% CI, 81–95), respectively. In both men and women, QTc≥460 ms after standing increased sensitivity (89% [95% CI, 83–94]) but decreased specificity (49% [95% CI, 41–57]). Sensitivity further increased (P<0.01) when a prolonged baseline QTc was accompanied by a QTc≥460 ms after standing in both men (93% [95% CI, 84–98]) and women (90% [95% CI, 81–96]). However, the area under the curve did not improve. T‐wave abnormalities after standing did not further increase the sensitivity or the area under the curve significantly.ConclusionsDespite earlier retrospective studies, a baseline ECG and the standing test in a prospective evaluation displayed a different diagnostic profile for congenital LQTS but no unequivocal synergism or advantage. This suggests that there is markedly reduced penetrance and incomplete expression in genetically confirmed LQTS with retention of repolarization reserve in response to the brief tachycardia provoked by standing. Show less
Peltenburg, P.J.; Pultoo, S.N.J.; Tobert, K.E.; Bos, J.M.; Lieve, K.V.V.; Tanck, M.; ... ; Werf, C. van der 2023
Aims In catecholaminergic polymorphic ventricular tachycardia (CPVT), the exercise-stress test (EST) is the cornerstone for the diagnosis, risk stratification, and assessment of therapeutic... Show moreAims In catecholaminergic polymorphic ventricular tachycardia (CPVT), the exercise-stress test (EST) is the cornerstone for the diagnosis, risk stratification, and assessment of therapeutic efficacy, but its repeatability is unknown. We aimed to test the repeatability of ventricular arrhythmia characteristics on the EST in patients with CPVT. Methods and results EST-pairs (ESTs performed within 18 months between 2005 and 2021, on the same protocol, and without or on the exact same treatment) of patients with RYR2-mediated CPVT from two specialized centres were included. The primary endpoint was the repeatability of the maximum ventricular arrhythmia score [VAS: 0 for the absence of premature ventricular contractions (PVCs); 1 for isolated PVCs; 2 for bigeminal PVCs; 3 for couplets; and 4 for non-sustained ventricular tachycardia]. Secondary outcomes were the repeatability of the heart rate at the first PVC and the Delta VAS (the absolute difference in VAS between the EST-pairs). A total of 104 patients with 349 EST-pairs were included. The median duration between ESTs was 343 (interquartile range, 189-378) days. Sixty (17.2%) EST-pairs were off therapy. The repeatability of the VAS was moderate {Krippendorf alpha, 0.56 [95% confidence interval (CI), 0.48-0.64]}, and the repeatability of the heart rate at the first PVC was substantial [intra-class correlation coefficient, 0.78 (95% CI, 0.71-0.84)]. The use of medication was associated with a higher odds for a Delta VAS > 1 (odds ratio = 3.52; 95% CI, 2.46-4.57; P = 0.020). Conclusion The repeatability of ventricular arrhythmia characteristics was moderate to substantial. This underlines the need for multiple ESTs in CPVT patients and CPVT suspicious patients and it provides the framework for assessing the therapeutic efficacy of novel CPVT therapies. Show less
Brugada syndrome (BrS) is a rare inherited arrhythmia syndrome. Affected children may experience life-threatening symptoms, mainly during fever. The percentage of SCN5A variant carriers in children... Show moreBrugada syndrome (BrS) is a rare inherited arrhythmia syndrome. Affected children may experience life-threatening symptoms, mainly during fever. The percentage of SCN5A variant carriers in children is higher than in adults. Current diagnostic and follow-up policies for children with (a family history of) BrS vary between centres. Here, we present a consensus statement based on the current literature and expert opinions to standardise the approach for all children with BrS and those from BrS families in the Netherlands. In summary, BrS is diagnosed in patients with a spontaneous type 1 electrocardiogram (ECG) pattern or with a Shanghai score >= 3.5 including >= 1 ECG finding. A sodium channel-blocking drug challenge test should only be performed after puberty with a few exceptions. A fever ECG is indicated in children with suspected BrS, in children with a first-degree family member with definite or possible BrS according to the Shanghai criteria with a SCN5A variant and in paediatric SCN5A variant carriers. In-hospital rhythm monitoring during fever is indicated in patients with an existing type 1 ECG pattern and in those who develop such a pattern. Genetic testing should be restricted to SCN5A. Children with BrS and children who carry an SCN5A variant should avoid medication listed at and fever should be suppressed. Ventricular arrhythmias or electrical storms should be treated with isoproterenol infusion. Show less
Background: Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. beta-Blockers decrease this risk, but studies... Show moreBackground: Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. beta-Blockers decrease this risk, but studies comparing individual beta-blockers in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of beta-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 beta-blocker initiation and age at start of beta-blocker therapy <18 years), treated with a beta-blocker were included. Cox regression analyses with time-dependent covariates for beta-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 beta-blocker (predominantly nadolol [n=140] or propranolol [n=70]) and 111 (33.7%) used a beta 1-selective beta-blocker (predominantly atenolol [n=51], metoprolol [n=33], or bisoprolol [n=19]) as initial beta-blocker. Baseline characteristics did not differ. The HRs for both the primary and secondary outcomes were higher for beta 1-selective compared with nonselective beta-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: beta 1-selective beta-blockers were associated with a significantly higher risk for arrhythmic events in symptomatic children with CPVT compared with nonselective beta-blockers, specifically nadolol. Nadolol, or propranolol if nadolol is unavailable, should be the preferred beta-blocker for treating symptomatic children with CPVT. Show less
Background: Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. beta-Blockers decrease this risk, but studies... Show moreBackground: Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. beta-Blockers decrease this risk, but studies comparing individual beta-blockers in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of beta-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 beta-blocker initiation and age at start of beta-blocker therapy <18 years), treated with a beta-blocker were included. Cox regression analyses with time-dependent covariates for beta-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 beta-blocker (predominantly nadolol [n=140] or propranolol [n=70]) and 111 (33.7%) used a beta 1-selective beta-blocker (predominantly atenolol [n=51], metoprolol [n=33], or bisoprolol [n=19]) as initial beta-blocker. Baseline characteristics did not differ. The HRs for both the primary and secondary outcomes were higher for beta 1-selective compared with nonselective beta-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: beta 1-selective beta-blockers were associated with a significantly higher risk for arrhythmic events in symptomatic children with CPVT compared with nonselective beta-blockers, specifically nadolol. Nadolol, or propranolol if nadolol is unavailable, should be the preferred beta-blocker for treating symptomatic children with CPVT. Show less
BACKGROUND Adult long QT syndrome (LQTS) patients have inadequate corrected QT interval (QTc) shortening and an abnormal T-wave response to the sudden heart rate acceleration provoked by standing.... Show moreBACKGROUND Adult long QT syndrome (LQTS) patients have inadequate corrected QT interval (QTc) shortening and an abnormal T-wave response to the sudden heart rate acceleration provoked by standing. In adults, this knowledge can be used to aid an LQTS diagnosis and, possibly, for risk stratification. However, data on the diagnostic value of the standing test in children are currently limited. OBJECTIVE To determine the potential value of the standing test to aid LQTS diagnostics in children. METHODS In a prospective cohort including children (<= 18 years) who had a standing test, comprehensive analyses were performed including manual and automated QT interval assessments and determination of T-wave morphology changes. RESULTS We included 47 LQTS children and 86 control children. At baseline, the QTc that identified LQTS children with a 90% sensitivity was 435 ms, which yielded a 65% specificity. A QTc >= 490 ms after standing only slightly increased sensitivity (91%, 95% confidence interval [CI]: 80%-98%) and slightly decreased specificity (58%, 95% CI: 47%-70%). Sensitivity increased slightly more when T-wave abnormalities were present (94%, 95% CI: 82%-99%; specificity 53%, 95% CI: 42%-65%). When a baseline QTc >= 440 ms was accompanied by a QTc >= 490 ms and T-wave abnormalities after standing, sensitivity further increased (96%, 95% CI: 85%-99%) at the expense of a further specificity decrease (41%, 95% CI: 30%-52%). Beat-to-beat analysis showed that 30 seconds after standing, LQTS children had a greater increase in heart rate compared to controls, which was more evidently present in LQTS boys and LQTS type 1 children. CONCLUSION In children, the standing test has limited additive diagnostic value for LQTS over a baseline electrocardiogram, while T-wave abnormalities after standing also have limited additional value. The standing test for LQTS should only be used with caution in children. Show less
