Risk Stratification in Pediatric Wolff-Parkinson-White: Practice Variation Among Pediatric Cardiologists and Electrophysiologists.

BACKGROUND: Published guidelines provide recommendations for risk stratification in pediatric Wolff-Parkinson-White (WPW). There are no data on provider concordance with these guidelines. We hypothesized that significant practice variation exists between pediatric cardiologists (PC) and electrophysiologists (EP). METHOD: The records of all patients, age 8 to 21 years, with a new ECG diagnosis of WPW between 1/1/2013 and 12/31/2018, from a single center, were retrospectively reviewed. Subjects were categorized on the basis of symptoms and resting ECG findings as one of the following: asymptomatic intermittent WPW, asymptomatic persistent WPW, or symptomatic WPW. The performance and results of diagnostic testing, including Holter monitor, event monitor, exercise stress test (EST), and electrophysiology study (EPS), were recorded. The primary outcome was concordance with published guidelines. A secondary outcome was documentation of a discussion of sudden cardiac death (SCD) risk. RESULTS: 615 patient encounters were analyzed in 231 patients with newly diagnosed WPW pattern on ECG (56% male; mean age at diagnosis 13.9 ± 2.5 years). EP were observed to have a significantly higher rate of guideline concordance than PC (95% vs. 71%, p < 0.001). There was significant practice variation between PC and EP in the documentation of a discussion of SCD risk: 96% in EP vs. 39% in PC (p < 0.001). CONCLUSION: Significant practice variation exists in the non-invasive and invasive risk stratification of pediatric WPW, with lower concordance to published guidelines amongst PC, when compared to EP. This report highlights the need to promote awareness of current WPW guidelines in the pediatric cardiology community at large.

Association of Weight With Ablation Outcomes in Pediatric Wolff-Parkinson-White: Analysis of the NCDR IMPACT Registry.

BACKGROUND: Guidelines for electrophysiology study (EPS) and catheter ablation in Wolff-Parkinson-White (WPW) are age based, but size may be a more relevant factor in determination of outcomes. OBJECTIVES: The goal of this study was to evaluate the association of patient weight with outcomes of catheter ablation for pediatric WPW. METHODS: A multicenter retrospective cohort study was performed on children aged 1 to 21 years with WPW and first-time EPS from April 2016 to December 2019 recorded in the IMPACT (Improving Pediatric and Adult Congenital Treatment) registry, excluding those with congenital heart disease, cardiomyopathy, and >1 ablation target. A weight threshold of 30 kg was selected, representing 1 SD below the cohort mean. The primary outcome was major adverse events (MAEs); additional outcomes included deferred ablation, use of cryoablation, and ablation success. RESULTS: A total of 4,456 subjects from 84 centers were evaluated, with 14% weighing <30 kg. Subjects weighing <30 kg were more likely to have preprocedural supraventricular tachycardia (45% vs 29%; P < 0.001) and less likely to have right septal accessory pathways (25% vs 33%; P < 0.001). MAEs were rare, although with higher incidence in the <30 kg cohort (0.3% vs 0.05%; P = 0.04). No difference was seen in likelihood of deferred ablation (9% vs 12%; P = 0.07) or use of cryoablation (11% vs 11%; P = 0.70). Success was higher in the <30 kg cohort: 95% vs 92% (P = 0.009). This effect persisted after adjusting for covariates (odds ratio: 1.6; 95% CI: 1.01-2.70; P = 0.046). CONCLUSIONS: Weight <30 kg was associated with a small but elevated risk of MAEs. Rates of deferred ablation and cryoablation were similar. Adjusting for factors (including accessory pathway type and location), weight <30 kg remained an independent predictor of acute success.

Impaired Dynamic Sarcoplasmic Reticulum Ca Buffering in Autosomal Dominant CPVT2.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal cardiac arrhythmia syndrome triggered by catecholamines released during exercise, stress, or sudden emotion. Variants in the calsequestrin-2 gene (CASQ2), encoding the major calcium (Ca) binding protein in the sarcoplasmic reticulum (SR), are the second most common cause of CPVT. Recently, several CASQ2 gene variants, such as CASQ2-K180R, have been linked to an autosomal dominant form of Casq2-linked CPVT (CPVT2), but the underlying mechanism is not known. METHODS: A K180R mouse model was generated using CRIPSR/Cas9. Heterozygous and homozygous K180R mice were studied using telemetry ECG recordings in vivo. Ventricular cardiomyocytes were isolated and studied using fluorescent Ca indicators and patch clamp. Expression levels and localization of SR Ca-handling proteins were evaluated using Western blotting and immunostaining. Intra-SR Ca kinetics were quantified using low-affinity Ca indicators. RESULTS: K180R mice exhibit an autosomal dominant CPVT phenotype following exercise or catecholamine stress. Upon catecholamine stress, K180R ventricular cardiomyocytes exhibit increased spontaneous SR Ca release events, triggering delayed afterdepolarizations and spontaneous beats. K180R had no effect on levels of Casq2, Casq2 polymers, or other SR Ca-handling proteins. Intra-SR Ca measurements revealed that K180R impaired dynamic intra-SR Ca buffering, resulting in a more rapid rise of free Ca in the SR during diastole. Steady-state SR Ca buffering and total SR Ca content were not changed. Consistent with the reduced dynamic intra-SR buffering, K180R causes reduced SR Ca release refractoriness. CONCLUSIONS: CASQ2-K180R causes CPVT2 via a heretofore unknown mechanism that differs from CASQ2 variants associated with autosomal recessive CPVT2. Unlike autosomal recessive CASQ2 variants, K180R impairs the dynamic buffering of Ca within the SR without affecting total SR Ca content or Casq2 protein levels. Our data provide insight into the molecular mechanism underlying autosomal dominant CPVT2.

Impact of Device Miniaturization on Insertable Cardiac Monitor Use in the Pediatric Population: An Analysis of the MarketScan Commercial and Medicaid Databases.

Background Insertable cardiac monitors (ICMs) are effective in the detection of paroxysmal arrhythmias. In 2014, the first miniaturized ICM was introduced with a less invasive implant technique. The impact of this technology on ICM use in pediatric patients has not been evaluated. We hypothesized an increase in annual pediatric ICM implants starting in 2014 attributable to device miniaturization. Methods and Results A retrospective observational study was conducted using administrative claims from MarketScan Medicaid and commercial insurance claims databases. Use of ICM between January 2013 and December 2018 was measured (normalized to the total enrolled population ≤18 years) and compared with balancing measures (Holter ambulatory monitors, cardiac event monitors, encounters with syncope diagnosis, implantation of implantable cardioverter-defibrillator/pacemaker). Secondary analyses included evaluations of subsequent interventions and complications. The study cohort included 33 532 185 individual subjects, of which 769 (0.002%) underwent ICM implantation. Subjects who underwent ICM implantation were 52% male sex, with a median age of 16 years (interquartile range, 10-17 years). A history of syncope was present in 71%, palpitations in 43%, and congenital heart disease in 28%. Following release of the miniaturized ICM, use of ICMs increased from 5 procedures per million enrollees in 2013 to 11 per million between 2015 and 2018 (P<0.001), while balancing measures remained static. Of 394 subjects with ≥1 year of follow-up after implantation, interventions included catheter ablation in 24 (6%), pacemaker implantation in 15 (4%), and implantable cardioverter-defibrillator implantation in 7 (2%). Conclusions Introduction of the miniaturized ICM was followed by a rapid increase in pediatric use. The effects on outcomes and value deserve further attention.

Comparison of Outcomes of Pediatric Catheter Ablation by Anesthesia Strategy: A Report From the NCDR IMPACT Registry.

[Figure: see text].

Can Pediatric Practitioners Correctly Interpret Electrocardiograms?

OBJECTIVES: To assess the impact of participation in an educational presentation on electrocardiogram (ECG) interpretation in children on pediatric practitioners' ability to accurately interpret ECGs. STUDY DESIGN: Pediatric healthcare providers at a pediatric clinic with >65 000 visits/year were eligible to participate. A 1-hour ECG educational module that provided a systematic approach to ECG interpretation was presented to 8 providers who consented (6 pediatricians, 2 pediatric nurse practitioners). A test on 11 ECGs (normal, normal-variant, and abnormal ECGs) was given before and 2 weeks after the educational module. Outcomes included correct interpretation of each ECG as normal or abnormal and correct identification of specific ECG findings. Data analysis was descriptive and included χ2 and Student t test. RESULTS: Mean score (SD) for correct interpretation of ECGs as normal or abnormal improved from 35% (48%) (95% CI 25.0-45.4) to 77% (42%) (95% CI 68.3-86.2) after the ECG educational module (P < .001). Mean (SD) pretest score for correct identification in the normal ECG category improved from 45% (50%) (95% CI 28.9-61.1) to 68% (47%) (95% CI 52.3-82.7) (P= .003). In the abnormal ECG category, correct identification improved from 31% (47%) (95% CI 17.6-44.9) to 83% (5%) (95% CI 72.4-94.3) after the module (P < .001). CONCLUSIONS: Education of pediatric practitioners on ECG interpretation significantly improves their ability to distinguish normal from abnormal and to identify specific abnormalities. Limitations included small sample size and short-term follow-up.

Cardiac Fibroma with Ventricular Tachycardia: An Unusual Clinical Presentation of Nevoid Basal Cell Carcinoma Syndrome.

Pediatric cardiac tumors are rare and often benign with an incidence of approximately 0.03-0.32% and can be associated with genetic conditions. For example, approximately 3% of individuals with nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, have a cardiac fibroma. NBCCS is also characterized by lamellar or early calcification of the falx, jaw keratocysts, palmar and/or plantar pits, and a predisposition for basal cell carcinomas. Given the management implications of NBCCS, including appropriate cancer screenings and precautions, prompt identification of affected individuals is critical. We report a case of a 6-year-old female presenting with ventricular tachycardia secondary to cardiac fibroma. After diagnosis of recurrent jaw keratocysts, she was clinically and molecularly diagnosed with NBCCS. Identification of a cardiac fibroma should prompt careful assessment of past medical and family history with consideration of a diagnosis of NBCCS.

Increased mitochondrial nanotunneling activity, induced by calcium imbalance, affects intermitochondrial matrix exchanges.

Exchanges of matrix contents are essential to the maintenance of mitochondria. Cardiac mitochondrial exchange matrix content in two ways: by direct contact with neighboring mitochondria and over longer distances. The latter mode is supported by thin tubular protrusions, called nanotunnels, that contact other mitochondria at relatively long distances. Here, we report that cardiac myocytes of heterozygous mice carrying a catecholaminergic polymorphic ventricular tachycardia-linked RyR2 mutation (A4860G) show a unique and unusual mitochondrial response: a significantly increased frequency of nanotunnel extensions. The mutation induces Ca2+ imbalance by depressing RyR2 channel activity during excitation-contraction coupling, resulting in random bursts of Ca2+ release probably due to Ca2+ overload in the sarcoplasmic reticulum. We took advantage of the increased nanotunnel frequency in RyR2A4860G+/- cardiomyocytes to investigate and accurately define the ultrastructure of these mitochondrial extensions and to reconstruct the overall 3D distribution of nanotunnels using electron tomography. Additionally, to define the effects of communication via nanotunnels, we evaluated the intermitochondrial exchanges of matrix-targeted soluble fluorescent proteins, mtDsRed and photoactivable mtPA-GFP, in isolated cardiomyocytes by confocal microscopy. A direct comparison between exchanges occurring at short and long distances directly demonstrates that communication via nanotunnels is slower.

Innovative cardiopulmonary resuscitation and automated external defibrillator programs in schools: Results from the Student Program for Olympic Resuscitation Training in Schools (SPORTS) study.

BACKGROUND: Bystander cardiopulmonary resuscitation (CPR) rates are low. Our study objective was to encourage Philadelphia high school students to develop CPR/AED (automated external defibrillator) training programs and to assess their efficacy. The focus was on developing innovative ways to learn the skills of CPR/AED use, increasing willingness to respond in an emergency, and retention of effective psychomotor resuscitation skills. METHODS AND RESULTS: Health education classes in 15 Philadelphia School District high schools were selected, with one Control and one Study Class per school. Both completed CPR/AED pre- and post-tests to assess cognitive knowledge and psychomotor skills. After pre-tests, both were taught CPR skills and AED use by their health teacher. Study Classes developed innovative programs to learn, teach, and retain CPR/AED skills. The study culminated with Study Classes competing in multiple CPR/AED skills events at the CPR/AED Olympic event. Outcomes included post-tests, Mock Code, and presentation scores. All students' cognitive and psychomotor skills improved with standard classroom education (p<0.001). Competition with other schools at the CPR/AED Olympics and the development of their own student-directed education programs resulted in remarkable retention of psychomotor skill scores in the Study Class (88%) vs the Control Class (79%) (p<0.001). Olympic participants averaged 93.1% on the Mock Code with 10 of 12 schools ≥94%. CONCLUSION: Students who developed creative and novel methods of teaching and learning resuscitation skills showed outstanding application of these skills in a Mock Code with remarkable psychomotor skill retention, potentially empowering a new generation of effectively trained CPR bystanders.

Cardiovascular deaths in children: general overview from the National Center for the Review and Prevention of Child Deaths.

BACKGROUND: Cardiovascular conditions rank sixth in causes of death in 1- to 19-year-olds. Our study is the first analysis of the cardiovascular death data set from the National Center for the Review and Prevention of Child Deaths, which provides the only systematic collection of cardiovascular deaths in children. METHODS: We developed an analytical data set from the National Center for the Review and Prevention of Child Deaths database for cardiovascular deaths in children 0 to 21 years old, reviewing 1,098 cases from 2005 to 2009 in 16 states who agreed to participate. RESULTS: Cardiovascular cases were aged 4.8 ± 6.6 years; 55.3%, ≤1 year; 24.6%, ≥10 years; male, 58%; white, 70.5%; black, 22.3%; Hispanic, 19.5%. Prior conditions were present in 48.5%: congenital heart disease, 23%; cardiomyopathies, 4.6%; arrhythmia, 1.7%; and congestive heart failure, 1.6%. Deaths occurred most frequently in urban settings, 49.2%; and in the hospital, 40.4%; home, 26.1%; or at school/work/sports, 4.8%. Emergency medical services were not evenly distributed with differences by age, race, ethnicity, and area. Autopsies (40.4%) occurred more often in those >10 years old (odds ratio [OR] 2.9), blacks (OR 1.6), or in those who died at school/work/sports (OR 3.9). The most common cardiovascular causes of death included congenital heart disease, 40.8%; arrhythmias, 27.1%; cardiomyopathy, 11.8%; myocarditis, 4.6%; congestive heart failure, 3.6%; and coronary artery anomalies, 2.2%. CONCLUSIONS: Our study identified differences in causes and frequencies of cardiovascular deaths by age, race, and ethnicity. Prevention of death may be impacted by knowledge of prior conditions, emergency plans, automated external defibrillator programs, bystander cardiopulmonary resuscitation education, and by a registry for all cardiovascular deaths in children.

Development of a data set of national cardiovascular deaths in the young.

BACKGROUND: The only systematic collection of cardiovascular (CV) deaths in children resides in the database derived from the Case Reporting System of the National Center for the Review and Prevention of Child Deaths (NCRPCD). We describe the process used to develop an analytical data set to inform our understanding of CV deaths in children from this database. METHODS: Twenty-five states reporting natural CV deaths during 2005 to 2009 were contacted. Sixteen states agreed to participate. Cases experienced a natural CV death and were 0 to 21 years. Challenges to building a final analytical data set were identified and included reclassification, recategorization, and the development of new variables from existing data, including an algorithm to identify sudden cardiac deaths. RESULTS: The final data set included 1,098 cases. Missing data comprised a mean of 41.7% for most key variables. Cardiovascular cases were aged 4.8 ± 6.6 years; 55.3%, ≤1 year, 24.6%, ≥10 years; male, 58%; white, 70.5%; black, 22.3%; and Hispanic, 19.5%. CONCLUSIONS: This manuscript provides the first description of the natural CV death data set from the NCRPCD. We identify potential beneficial changes in the NCRPCD Case Reporting System and review process. Analysis of these data will help determine characteristics of CV deaths and allow the assessment of risk factors that can be used to prevent CV death in the young. The rate of CV death can be lowered using knowledge of associations that can be gleaned from this robust database. Best practices for prevention hold promise for a future with fewer deaths that will need to be reviewed.

Prevalence of electrocardiogram use in infants with apparent life-threatening events: a multicenter database study.

OBJECTIVE: An apparent life-threatening event (ALTE) is a common diagnosis in pediatrics, but there is no standardized method to evaluate these patients. We sought to determine the prevalence of electrocardiogram (ECG) use in patients presenting to children's hospitals with an ALTE. METHODS: The data from the Pediatric Health Information System database from 43 children's hospitals were collected during a 15-month period between October 2009 and December 2010. Patients were included if they were younger than 1 year at the time of presentation. Demographic data, including age, length of hospital stay, second ALTE, and survival, were recorded, along with the prevalence of ECGs and International Classification of Diseases, Ninth Revision, cardiac diagnoses. RESULTS: There were 2179 patients with an ALTE, with a mean age of 65.7 days old and length of stay of 3.4 days. A total of 947 (43%) of these patients received an ECG. The prevalence of ECG use and cardiac diagnoses were variable among the participating hospitals. Depending on the institution, 0% to 93% of patients had an ECG, and 4% to 39% of patients had an International Classification of Diseases, Ninth Revision, cardiac diagnosis. CONCLUSIONS: Electrocardiograms are performed in fewer than half of patients with ALTE presenting to children's hospitals. There is wide variation in the prevalence of ECG use as a diagnostic tool for infants presenting with an ALTE.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D).

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a progressive genetic cardiomyopathy characterized by progressive fatty and fibrous replacement of ventricular myocardium. The clinical presentation is marked by ventricular arrhythmias, some fatal. The disease has evolved from a primary electrical/electrophysiological disorder (in the 1980s-1990s) to a diagnostic imaging conundrum (in the 2000s) to the current day understanding of a genetic cardiomyopathy caused by defects in cell-cell adhesion proteins or intracellular signaling components. The pathogenesis, clinical presentation, and the genetics of the disease are discussed in this review.

Ultrastructure of cardiac muscle in reptiles and birds: optimizing and/or reducing the probability of transmission between calcium release units.

It is known that cardiac myocytes contain three categories of calcium release units (CRUs) all bearing arrays of RyR2: peripheral couplings, constituted of an association of the junctional SR (jSR) with the plasmalemma; dyads, associations between jSR and T tubules; internal extended junctional jSR (EjSR)/corbular jSR that is not associated with plasmalemma/T tubules. The bird hearts, even if fast beating (e.g., in finch and hummingbird) have no T tubules, despite fiber sizes comparable to those of mammalian ventricle, but are rich in EjSR/corbular SR. The heart of small lizard also lacks T tubule, but it has only peripheral couplings and compensates for lack of internal CRUs by the small diameter of its cells. We have extended previous information on chicken heart to finch and lizard by establishing a spatial relationship between RyR2 clusters in jSR of peripheral couplings and clusters of intra-membrane particles identifiable as voltage sensitive calcium channels (CaV1.2) in the adjacent plasmalemma. This provides the structural basis for initiation of the heart beat in all three species. Further we evaluated the distances separating peripheral couplings from each other and between EjSR/corbular SR sites within the bird muscles in all three hearts. The distances suggest that peripheral coupling sites are most likely to act independently of each other and that a calcium wave-front propagation from one internal CRU site to the other across the level of the Z line, may be marginally successful in the chicken, but certainly very effective in the finch.

Managing arrhythmias before and after aortic valve surgery in children.

The proximity of the coronary arteries and the bundle of His to the aortic valve may contribute to the pathogenesis of arrhythmias in patients with aortic valve disease. Severe aortic valve disease may also adversely alter left ventricular hemodynamics (end-diastolic dimensions and wall stress) and thus create a substrate for ventricular arrhythmias before any intervention is performed. The severity of these arrhythmias depends on the severity of the underlying substrate (or the specific problem, such as aortic stenosis or aortic regurgitation), the age at which the aortic valve intervention was performed, the type of intervention (i.e. transcatheter aortic valve interventions or open aortic valve replacement or repair), and the reversibility of the altered hemodynamics after surgery. Both bradyarrhythmias and tachyarrhythmias are known complications of aortic valve interventions. Although data are scant, this review summarizes the incidence of arrhythmias before and after aortic valve interventions from a pediatric perspective.

Genotype- and mutation site-specific QT adaptation during exercise, recovery, and postural changes in children with long-QT syndrome.

BACKGROUND: Exercise stress testing has shown diagnostic utility in adult patients with long-QT syndrome (LQTS); however, the QT interval adaptation in response to exercise in pediatric patients with LQTS has received little attention. METHODS AND RESULTS: One-hundred fifty-eight patients were divided into 3 groups: Those with LQTS type 1 (LQT1) or LQTS type 2 (LQT2) and normal control subjects without cardiovascular disease. Each patient underwent a uniform exercise protocol with a cycle ergometer followed by a 9-minute recovery phase with continuous 12-lead ECG monitoring. Each patient underwent a baseline ECG while resting in the supine position and in a standstill position during continuous ECG recording to determine changes in the QT and RR intervals. Fifty patients were gene-positive for LQTS (n=29 for LQT1 and n=21 for LQT2), and the control group consisted of 108 patients. QT interval adaptation was abnormal in the LQT1 patients compared with LQT2 and control patients (P<0.001). A corrected QT interval (QTc) >460 ms in the late recovery phase at 7 minutes predicted LQT1 or LQT2 versus control subjects with 96% specificity, 86% sensitivity, and a 91% positive predictive value. A recovery ΔQTc((7 min-1 min)) >30 ms predicted LQT2 versus LQT1 with 75% sensitivity, 82% specificity, and a 75% positive predictive value. The postural ΔQT was significantly different between LQTS and control groups (P=0.005). CONCLUSIONS: Genotype-specific changes in repolarization response to exercise and recovery exist in the pediatric population and are of diagnostic utility in LQTS. An extended recovery phase is preferable to assess the repolarization response after exercise in the pediatric population.