An international multicenter cohort study on implantable cardioverter-defibrillators for the treatment of symptomatic children with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) may cause sudden cardiac death (SCD) despite medical therapy. Therefore, implantable cardioverter-defibrillators (ICDs) are commonly advised. However, there are limited data on the outcomes of ICD use in children. OBJECTIVE: The purpose of this study was to compare the risk of arrhythmic events in pediatric patients with CPVT with and without ICD. METHODS: We compared the risk of SCD in patients with RYR2 (ryanodine receptor 2) variants and phenotype-positive symptomatic patients with CPVT with and without ICD who were younger than 19 years and had no history of sudden cardiac arrest at phenotype diagnosis. The primary outcome was SCD; secondary outcomes were composite end points of SCD, sudden cardiac arrest, or appropriate ICD shocks with or without arrhythmic syncope. RESULTS: The study included 235 patients, 73 with ICD (31.1%) and 162 without ICD (68.9%). Over a median follow-up of 8.0 years (interquartile range 4.3-13.4 years), SCD occurred in 7 patients (3.0%), of whom 4 (57.1%) were noncompliant with medications and none had an ICD. Patients with ICD had a higher risk of both secondary composite outcomes (without syncope: hazard ratio 5.85; 95% confidence interval 3.40-10.09; P < .0001; with syncope: hazard ratio 2.55; 95% confidence interval 1.50-4.34; P = .0005). Thirty-one patients with ICD (42.5%) experienced appropriate shocks, 18 (24.7%) inappropriate shocks, and 21 (28.8%) device-related complications. CONCLUSION: SCD events occurred only in the no ICD group and in those not on optimal medical therapy. Patients with ICD had a high risk of appropriate and inappropriate shocks, which may be reduced with appropriate device programming. Severe ICD complications were common, and risks vs benefits of ICDs need to be considered.

Pharmacological Management of Cardiac Arrhythmias in the Fetal and Neonatal Periods: A Scientific Statement From the American Heart Association: Endorsed by the Pediatric & Congenital Electrophysiology Society (PACES).

Disorders of the cardiac rhythm may occur in both the fetus and neonate. Because of the immature myocardium, the hemodynamic consequences of either bradyarrhythmias or tachyarrhythmias may be far more significant than in mature physiological states. Treatment options are limited in the fetus and neonate because of limited vascular access, patient size, and the significant risk/benefit ratio of any intervention. In addition, exposure of the fetus or neonate to either persistent arrhythmias or antiarrhythmic medications may have yet-to-be-determined long-term developmental consequences. This scientific statement discusses the mechanism of arrhythmias, pharmacological treatment options, and distinct aspects of pharmacokinetics for the fetus and neonate. From the available current data, subjects of apparent consistency/consensus are presented, as well as future directions for research in terms of aspects of care for which evidence has not been established.

Management of Junctional Rhythm in Patients After the Fontan Operation: A Multicenter Congenital Cardiology Survey.

Sinus node dysfunction with concomitant junctional rhythm (JR) is frequently observed among Fontan patients and has been recognized as a contributor to heart failure. The impact and management of JR is unclear. A survey was mailed to all members of the Pediatric and Congenital Electrophysiology society (PACES) and members were asked to forward the questionnaire to their non-electrophysiology colleagues. Responses were received from 154 physicians (88 electrophysiologists (EP's) and 66 non-EP's (46 pediatric cardiologists and 20 adult congenital cardiologists). There were few differences in the response between EP's and non-EP's. Overall, 57% recommended an annual ambulatory ECG (AECG). A significant majority (80%) opted to continue to follow patients with significant periods of JR on AECG as long as the patients were asymptomatic, and showed no echocardiographic signs of cardiac decompensation. However, 84% would place a pacemaker in a patient with JR who was having open chest surgery for other reasons. Finally, pacemaker placement would be performed by 91% if a patient with JR showed signs of heart failure. Most congenital cardiologists would not recommend pacemaker placement in asymptomatic Fontan patients with JR. Further studies are needed on the Fontan population to determine the impact of SND and JR on longer term outcomes and to determine the role and optimal timing of pacemaker placement in these patients.

Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P<0.001). CONCLUSIONS: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy.

Patterns of Electrocardiographic Abnormalities in Children with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), a common cardiomyopathy in children, is an important cause of morbidity and mortality. Early recognition and appropriate management are important. An electrocardiogram (ECG) is often used as a screening tool in children to detect heart disease. The ECG patterns in children with HCM are not well described.ECGs collected from an international cohort of children, and adolescents (≤ 21 years) with HCM were reviewed. 482 ECGs met inclusion criteria. Age ranged from 1 day to 21 years, median 13 years. Of the 482 ECGs, 57 (12%) were normal. The most common abnormalities noted were left ventricular hypertrophy (LVH) in 108/482 (22%) and biventricular hypertrophy (BVH) in 116/482 (24%) Of the patients with LVH/BVH (n = 224), 135 (60%) also had a strain pattern (LVH in 83, BVH in 52). Isolated strain pattern (in the absence of criteria for hypertrophy) was seen in 43/482 (9%). Isolated pathologic Q waves were seen in 71/482 (15%). Pediatric HCM, 88% have an abnormal ECG. The most common ECG abnormalities were LVH or BVH with or without strain. Strain pattern without hypertrophy and a pathologic Q wave were present in a significant proportion (24%) of patients. Thus, a significant number of children with HCM have ECG abnormalities that are not typical for "hypertrophy". The presence of the ECG abnormalities described above in a child should prompt further examination with an echocardiogram to rule out HCM.

Hemodynamic Impact of Atrial Pacing in Patients with Fontan Physiology and Junctional Rhythm: A Cardiac Catheterization Study.

Sinus node dysfunction is a common problem and adversely impacts patients who have undergone the Fontan operation. In Fontan patients with an adequate junctional escape rhythm, the benefit of atrial pacing to restore atrioventricular synchrony remains unclear. Data were collected retrospectively on all Fontan patients with junctional rhythm who underwent atrial pacing during cardiac catheterization. Hemodynamics were obtained at baseline and after atrial pacing for 5-10 min. Seven patients, mean age 10 years (3-21) were studied. The type of Fontan was extracardiac in 6 and lateral tunnel in one. Patients were paced at 10 bpm faster than their junctional rate. With pacing, there was a significant decrease in left atrial pressure from (mean ± SEM) 8.8 ± 2.6 to 5.5 ± 2.9 mmHg (p = 0.02), a significant increase in cardiac index from 2.7 ± 0.8 to 3.5 ± 1 L/min/m2 (p = 0.01) and pulmonary blood flow from 2.1 ± 0.6 to 2.7 ± 0.7 L/min/m2 (p = 0.001), and no significant change in pulmonary artery pressure, from 13.4 ± 2.8 to 12.4 mmHg ± 3.6 (p = 0.06) or pulmonary vascular resistance from 2.1 ± 0.86 to 3.25 ± 1.9 WU × M2 (p = 0.1). In Fontan patients with junctional rhythm, atrial pacing decreased the left atrial pressure, increased cardiac output and did not significantly change the pulmonary artery pressure. Our study supports further investigation into the utility of prophylactic atrial pacemaker implantation in Fontan patients with significant durations of JR on ambulatory monitoring.

Timely Use of Venous-Arterial ECMO to Treat Congenital Pediatric Junctional Ectopic Tachycardia: A Case Report.

Supraventricular tachycardia is the most common tachyarrhythmia in pediatrics. Although postoperative junctional ectopic tachycardia (JET) is a known complication of congenital heart surgery that is typically transient, congenital JET is rare and requires aggressive treatment to maintain hemodynamic stability. We describe the case of a 3-month-old, previously healthy female who presented with heart failure and cardiogenic shock secondary to congenital JET for whom extracorporeal membrane oxygenation (ECMO) provided time for selection of effective therapy. Adenosine, cardioversion, and transesophageal pacing were unsuccessful, and her echocardiogram demonstrated bilateral atrial dilation and severe left ventricular systolic dysfunction. Approximately 8 hours after presentation, venous-arterial ECMO was commenced allowing for successful treatment with amiodarone. Her electrocardiogram demonstrated atrioventricular dissociation consistent with JET. She was successfully decannulated from ECMO after 6 days. Her discharge echocardiogram showed normal ventricular function, and she had no significant ECMO sequelae. This case demonstrates the value of early ECMO initiation for cardiovascular support in pediatric patients with a life-threatening arrhythmia and in cardiogenic shock. ECMO support can allow for full diagnostic and therapeutic decisions to effectively reverse the consequences of uncontrolled arrhythmias unrelated to surgical complications.

Pulmonary Cusp Positioning of a Right Ventricular Outflow Tract Ventricular Tachycardia in a Pediatric Patient Identified Using Intracardiac Echocardiography.

Ventricular premature beats originating from the right ventricular outflow tract can have myocardial extensions to the pulmonary valve and pulmonary artery. Treatment may consist of catheter ablation combined with the use of three-dimensional mapping to determine the exact location of ectopy. The location of ectopy relative to the pulmonary valve may be hard to ascertain. Intracardiac echocardiography (ICE) is a noninvasive approach by which one can determine the relationship of the pulmonary valve relative to the ablation catheter prior to ablation. ICE has achieved increasing popularity during the ablation of other arrhythmias such as tricuspid valve arrhythmias and has been shown to be helpful in guiding catheter placement prior to ablation. The additional information gained from deploying ICE may ensure more precise ablation, prevent theoretical damage to the pulmonary valve, and alleviate the need for a repeat procedure. Here, we present a case involving the use of ICE during a pediatric patient's second ablation procedure to precisely determine the location of ectopy of nonsustained ventricular tachycardia originating from the distal pulmonary valve.

Exercise-induced syncope and Brugada syndrome.

Brugada syndrome (BrS) is a hereditary condition that is characterized by ST elevation, ventricular tachycardia or fibrillation, and sudden cardiac death in otherwise healthy patients. Life-threatening arrhythmias generally occur, while at rest, with fever or during vagotonic states. Exercise is generally not considered a trigger for ventricular arrhythmias or syncope in patients with BrS. We describe a patient who presented with exercise-induced syncope, ventricular tachycardia during an exercise test, and was found to be both genotypically and phenotypically positive for BrS. This case highlights a potentially important role of exercise testing in diagnosing and risk stratifying certain patients with BrS.

Impact of Obesity on Left Ventricular Thickness in Children with Hypertrophic Cardiomyopathy.

Obesity is associated with additional left ventricular hypertrophy (LVH) in adults with hypertrophic cardiomyopathy (HCM). It is not known whether obesity can lead to further LVH in children with HCM. Echocardiographic LV dimensions were determined in 504 children with HCM. Measurements of interventricular septal thickness (IVST) and posterior wall thickness (PWT), and patients' weight and height were recorded. Obesity was defined as a body mass index (BMI) ≥ 99th percentile for age and sex. IVST data was available for 498 and PWT data for 484 patients. Patient age ranged from 2 to 20 years (mean ± SD, 12.5 ± 3.9) and 340 (68%) were males. Overall, patient BMI ranged from 7 to 50 (22.7 ± 6.1). Obesity (BMI 18-50, mean 29.1) was present in 140 children aged 2-19.6 (11.3 ± 4.1). The overall mean IVST was 20.5 ± 9.6 mm and the overall mean PWT was 11.0 ± 8.4 mm. The mean IVST in the obese patients was 21.6 ± 10.0 mm and mean PWT was 13.3 ± 14.7 mm. The mean IVST in the non-obese patients was 20.1 ± 9.5 mm and mean PWT was 10.4 ± 4.3 mm. Obesity was not significantly associated with IVST (p = 0.12), but was associated with increased PWT (0.0011). Obesity is associated with increased PWT but not IVST in children with HCM. Whether obesity and its impact on LVH influences clinical outcomes in children with HCM needs to be studied.

Risk factors for lethal arrhythmic events in children and adolescents with hypertrophic cardiomyopathy and an implantable defibrillator: An international multicenter study.

BACKGROUND: Predictors of risk of lethal arrhythmic events (LAE) is poorly understood and may differ from adults in children with hypertrophic cardiomyopathy (HCM). OBJECTIVE: The purpose of this study was to determine predictors of LAE in children with HCM. METHODS: A retrospective data collection was performed on 446 children and teenagers 20 years and younger (290 [65%] male; mean age 10.1 ± 5.7 years) with idiopathic HCM from 35 centers. Patients were classified as group 1 (HCM with LAE) if having a secondary prevention implantable cardioverter-defibrillator (ICD) or primary prevention ICD with appropriate interventions or group 2 (HCM without LAE) if having a primary prevention ICD without appropriate interventions. RESULTS: There were 152 children (34%) in group 1 and 294 (66%) in group 2. Risk factors for group 1 by univariate analysis were septal thickness, posterior left ventricular (LV) wall thickness, lower LV outflow gradient, and Q wave > 3 mm in inferior electrocardiographic leads. Factors not associated with LAE were family history of SCD, abnormal blood pressure response to exercise, and ventricular tachycardia on ambulatory electrocardiographic monitoring. Risk factors for SCD by multivariate analysis were age at ICD placement (hazard ratio [HR] 0.9; P = .0025), LV posterior wall thickness z score (HR 1.02; P < .005), and LV outflow gradient < 30 mm Hg (HR 2.0; P < .006). LV posterior wall thickness z score ≥ 5 was associated with LAE. CONCLUSION: Risk factors for LAE appear different in children compared to adults. Conventional adult risk factors were not significant in children. Further prospective studies are needed to improve risk stratification for LAE in children with HCM.

Fetal arrhythmias: Diagnosis and management.

This article reviews important features for improving the diagnosis and management of fetal arrhythmias. The normal fetal heart rate ranges between 110 and 160 beats per minute. A fetal heart rate is considered abnormal if the heart rate is beyond the normal ranges or the rhythm is irregular. The rate, duration, and origin of the rhythm and degree of irregularity usually determine the potential for hemodynamic consequences. Most of the fetal rhythm disturbances are the result of premature atrial contractions (PACs) and are of little clinical significance. Other arrhythmias include tachyarrhythmias (heart rate in excess of 160 beats/min) such as atrioventricular (AV) reentry tachycardia, atrial flutter, and ventricular tachycardia, and bradyarrhythmias (heart rate <110 beats/min) such as sinus node dysfunction, complete heart block (CHB) and long QT syndrome (which is associated with sinus bradycardia and pseudo-heart block).

A prospective 5-year study of exercise performance following Melody valve implant.

BACKGROUND: The long-term benefits of Melody valve implant for right ventricular outflow tract conduit obstruction or insufficiency on exercise capacity are undefined. METHODS: As part of the Melody valve clinical trial, 136 patients with congenital heart disease underwent serial cardiopulmonary exercise testing prior to, 6 months after, and annually for up to 5 years postimplant. RESULTS: Mean age at Melody valve implantation was 22.4 ± 0.9 years (range 7-53 years). The 95 patients who completed the study protocol provide the basis of this report. An initial improvement in % predicted workload was present at 6 months postimplant; however, at the final (5 year) follow-up, sustained or further improvements in workload were not demonstrated for the entire cohort compared to baseline. By subgroup analysis, age <17 years at implant and pulmonary regurgitation as the primary lesion were variables associated with sustained improvement in exercise performance. There were sustained improvements in the ventilatory equivalents for O2 (minute ventilation/O2 intake, P = .01) and CO2 (minute ventilation/CO2 output, P < .01) at the ventilatory anaerobic threshold at the study conclusion. Improvements in forced vital capacity were also observed during the study but not sustained at the final follow-up. CONCLUSIONS: A cautious appraisal of the cardiovascular benefits of Melody valve implant on sustained improvements in exercise performance appears warranted. Although the observed changes in pulmonary function suggest improved restrictive lung physiology and more efficient gas exchange, after an initial increase in % predicted performance, neither sustained nor further improvements in exercise performance were observed, except in specific patient subgroups.

Catecholaminergic polymorphic ventricular tachycardia patients with multiple genetic variants in the PACES CPVT Registry.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is often a life-threatening arrhythmia disorder with variable penetrance and expressivity. Little is known about the incidence or outcomes of CPVT patients with ≥2 variants. METHODS: The phenotypes, genotypes and outcomes of patients in the Pediatric and Congenital Electrophysiology Society CPVT Registry with ≥2 variants in genes linked to CPVT were ascertained. The American College of Medical Genetics & Genomics (ACMG) criteria and structural mapping were used to predict the pathogenicity of variants (3D model of pig RyR2 in open-state). RESULTS: Among 237 CPVT subjects, 193 (81%) had genetic testing. Fifteen patients (8%) with a median age of 9 years (IQR 5-12) had ≥2 variants. Sudden cardiac arrest occurred in 11 children (73%), although none died during a median follow-up of 4.3 years (IQR 2.5-6.1). Thirteen patients (80%) had at least two RYR2 variants, while the remaining two patients had RYR2 variants plus variants in other CPVT-linked genes. Among all variants identified, re-classification of the commercial laboratory interpretation using ACMG criteria led to the upgrade from variant of unknown significance (VUS) to pathogenic/likely pathogenic (P/LP) for 5 variants, and downgrade from P/LP to VUS for 6 variants. For RYR2 variants, 3D mapping using the RyR2 model suggested that 2 VUS by ACMG criteria were P/LP, while 2 variants were downgraded to likely benign. CONCLUSIONS: This severely affected cohort demonstrates that a minority of CPVT cases are related to ≥2 variants, which may have implications on family-based genetic counselling. While multi-variant CPVT patients were at high-risk for sudden cardiac arrest, there are insufficient data to conclude that this genetic phenomenon has prognostic implications at present. Further research is needed to determine the significance and generalizability of this observation. This study also shows that a rigorous approach to variant re-classification using the ACMG criteria and 3D mapping is important in reaching an accurate diagnosis, especially in the multi-variant population.

Predictors of electrocardiographic screening failure for the subcutaneous implantable cardioverter-defibrillator in children: A prospective multicenter study.

BACKGROUND: Subcutaneous implantable cardioverter-defibrillator (SICD) shows promise for select patients at risk of sudden cardiac death. However, patients need to pass an electrocardiographic (ECG) screening (ECG-S) test before they can receive an SICD. Predictors of ECG-S failure in children are unclear. OBJECTIVE: The purpose of this study was to identify the incidence and predictive factors for failure of ECG-S in children. METHODS: Patients 18 years and younger with a preexisting ICD underwent ECG-S for SICD. ECG and demographic data were analyzed for factors predictive of failure. RESULTS: Seventy-three patients (mean age 14.2 ± 3.3 years; range 5-18 years) with hypertrophic cardiomyopathy (n = 24, 33%), long QT syndrome (n =18, 25%), other inherited arrhythmia syndromes (n = 20, 27%), congenital heart disease (n = 9, 12%), and miscellaneous conditions (n = 2) with an existing transvenous ICD underwent prospective ECG-S. Nineteen (26%) failed ECG-S. Failed patients had a longer corrected QT (QTc) interval (457 ms vs 425 ms; P = .03), a longer QRS duration (120 ms vs 98 ms; P = .04), and a lower ratio of R-wave to T-wave amplitudes (R:T ratio) in lead aVF (4 vs 5; P = .001). Multivariable logistic regression identified QTc interval (odds ratio [OR] 4.31; P = .04), QRS duration (OR 4.93; P = .03), R:T ratio in lead aVF (OR 3.13; P = .08) as predictors of failure. A risk score with 1 point each for QTc interval >440 ms, QRS duration >120 ms, and R:T ratio <6.5 in lead aVF was associated with probability of failure of 15.4% (1 point), 47.4% (2 points), and 88.6% (3 points), respectively. CONCLUSION: ECG-S failure for SICD occurred in 26% of children, which is higher than the reported incidence in adults. Factors predicting ECG-S failure included longer QTc interval, longer QRS duration, and lower R:T ratio in lead aVF.