Eric S. Silver

Variation in Perioperative Care across Centers for Infants Undergoing the Norwood Procedure

OBJECTIVES In the Single Ventricle Reconstruction trial, infants undergoing the Norwood procedure were randomly allocated to undergo a right ventricle-to-pulmonary artery shunt or a modified Blalock-Taussig shunt. Apart from shunt type, subjects received the local standard of care. We evaluated variation in perioperative care during the Norwood hospitalization across 14 trial sites. METHODS Data on preoperative, operative, and postoperative variables for 546 enrolled subjects who underwent the Norwood procedure were collected prospectively on standardized case report forms, and variation across the centers was described. RESULTS Gestational age, birth weight, and proportion with hypoplastic left heart syndrome were similar across sites. In contrast, all recorded variables related to preoperative care varied across centers, including fetal diagnosis (range, 55%-85%), preoperative intubation (range, 29%-91%), and enteral feeding. Perioperative and operative factors were also variable across sites, including median total support time (range, 74-189 minutes) and other perfusion variables, arch reconstruction technique, intraoperative medication use, and use of modified ultrafiltration (range, 48%-100%). Additional variation across centers was seen in variables related to postoperative care, including proportion with an open sternum (range, 35%-100%), median intensive care unit stay (range, 9-44 days), type of feeding at discharge, and enrollment in a home monitoring program (range, 1%-100%; 5 sites did not have a program). Overall, in-hospital death or transplant occurred in 18% (range across sites, 7%-39%). CONCLUSIONS Perioperative care during the Norwood hospitalization varies across centers. Further analysis evaluating the underlying causes and relationship of this variation to outcome is needed to inform future studies and quality improvement efforts.

A Novel and Lethal De Novo LQT-3 Mutation in a Newborn with Distinct Molecular Pharmacology and Therapeutic Response

Background SCN5A encodes the α-subunit (Nav1.5) of the principle Na+ channel in the human heart. Genetic lesions in SCN5A can cause congenital long QT syndrome (LQTS) variant 3 (LQT-3) in adults by disrupting inactivation of the Nav1.5 channel. Pharmacological targeting of mutation-altered Na+ channels has proven promising in developing a gene-specific therapeutic strategy to manage specifically this LQTS variant. SCN5A mutations that cause similar channel dysfunction may also contribute to sudden infant death syndrome (SIDS) and other arrhythmias in newborns, but the prevalence, impact, and therapeutic management of SCN5A mutations may be distinct in infants compared with adults. Methods and Results Here, in a multidisciplinary approach, we report a de novo SCN5A mutation (F1473C) discovered in a newborn presenting with extreme QT prolongation and differential responses to the Na+ channel blockers flecainide and mexiletine. Our goal was to determine the Na+ channel phenotype caused by this severe mutation and to determine whether distinct effects of different Na+ channel blockers on mutant channel activity provide a mechanistic understanding of the distinct therapeutic responsiveness of the mutation carrier. Sequence analysis of the proband revealed the novel missense SCN5A mutation (F1473C) and a common variant in KCNH2 (K897T). Patch clamp analysis of HEK 293 cells transiently transfected with wild-type or mutant Na+ channels revealed significant changes in channel biophysics, all contributing to the probands phenotype as predicted by in silico modeling. Furthermore, subtle differences in drug action were detected in correcting mutant channel activity that, together with both the known genetic background and age of the patient, contribute to the distinct therapeutic responses observed clinically. Significance The results of our study provide further evidence of the grave vulnerability of newborns to Na+ channel defects and suggest that both genetic background and age are particularly important in developing a mutation-specific therapeutic personalized approach to manage disorders in the young.

Comparison of Fontan Survivors with and without Pacemakers: A Report from the Pediatric Heart Network Fontan Cross‐sectional Study

OBJECTIVE Although many Fontan patients undergo pacemaker placement, there are few studies characterizing this population. Our purpose was to compare clinical characteristics, functional status and measures of ventricular performance in Fontan patients with and without a pacemaker. PATIENTS AND DESIGN The National Heart, Lung, and Blood Institute funded Pediatric Heart Network Fontan Cross-Sectional Study characterized 546 Fontan survivors. Clinical characteristics, medical history and study outcomes (Child Health Questionnaire [CHQ]), echocardiographic evaluation of ventricular function, and exercise testing) were compared between subjects with and without pacemakers. RESULTS Of 71 subjects with pacemakers (13%), 43/71 (61%) were in a paced rhythm at the time of study enrollment (age 11.9 ± 3.4 years). Pacemaker subjects were older at study enrollment, more likely to have single left ventricles, and taking more medications. There were no differences in age at Fontan or Fontan type between the pacemaker and no pacemaker groups. There were no differences in exercise performance between groups. CHQ physical summary scores were lower in the pacemaker subjects (39.7 ± 14.3 vs. 46.1 ± 11.2, P =.001). Ventricular ejection fraction z-score was also lower (-1.4 ± 1.9 vs. -0.8 ± 2.0, P =.05) in pacemaker subjects. CONCLUSIONS In our cohort of Fontan survivors, those with a pacemaker have poorer functional status and evidence of decreased ventricular systolic function compared to Fontan survivors without a pacemaker.

Coronary Artery Spasm During Radiofrequency Ablation of a Left Lateral Accessory Pathway

A 16-year-old female patient with Wolff-Parkinson-White syndrome and supraventricular tachycardia underwent radiofrequency (RF) catheter ablation of an accessory pathway in the left lateral area. During RF ablation she developed reversible ST segment elevation secondary to coronary artery spasm. Coronary angiography demonstrated the ablation catheter in close proximity to the circumflex coronary artery, with no evidence of coronary artery injury. Subsequently, conduction by way of the accessory pathway was successfully eliminated with cryoablation with no further coronary spasm or injury.

Implantation of Permanent Pacemaker and ICD Leads in Children Using a Three-Dimensional Electroanatomic Mapping System as an Aid to Fluoroscopy

Three‐dimensional electroanatomic mapping systems (3D mapping) allow the creation of an anatomic representation of the cardiac anatomy and real‐time monitoring of transvenous pacing catheters. Their use to facilitate pacemaker (PM) and implantable cardioverter defibrillator (ICD) lead placement in the pediatric population has not been well defined. We sought to review our experience using 3D mapping as an adjunct to fluoroscopy for positioning of permanent PM and ICD leads in pediatric patients.

Development and impact of arrhythmias after the Norwood procedure: A report from the Pediatric Heart Network

Objectives: The study objective was to determine the predictors of new‐onset arrhythmia among infants with single‐ventricle anomalies during the post‐Norwood hospitalization and the association of those arrhythmias with postoperative outcomes (ventilator time and length of stay) and interstage mortality. Methods: After excluding patients with preoperative arrhythmias, we used data from the Pediatric Heart Network Single Ventricle Reconstruction Trial to identify risk factors for tachyarrhythmias (atrial fibrillation, atrial flutter, supraventricular tachycardia, junctional ectopic tachycardia, and ventricular tachycardia) and atrioventricular block (second or third degree) among 544 eligible patients. We then determined the association of arrhythmia with outcomes during the post‐Norwood hospitalization and interstage period, adjusting for identified risk factors and previously published factors. Results: Tachyarrhythmias were noted in 20% of subjects, and atrioventricular block was noted in 4% of subjects. Potentially significant risk factors for tachyarrhythmia included the presence of modified Blalock–Taussig shunt (P = .08) and age at Norwood (P = .07, with risk decreasing each day at age 8‐20 days); the only significant risk factor for atrioventricular block was undergoing a concomitant procedure at the time of the Norwood (P = .001), with the greatest risk being in those undergoing a tricuspid valve procedure. Both tachyarrhythmias and atrioventricular block were associated with longer ventilation time and length of stay (P < .001 for all analyses). Tachyarrhythmias were not associated with interstage mortality; atrioventricular block was associated with mortality among those without a pacemaker in the unadjusted analysis (hazard ratio, 2.3; P = .02), but not after adding covariates. Conclusions: Tachyarrhythmias are common after the Norwood procedure, but atrioventricular block may portend a greater risk for interstage mortality.

The “hidden” concealed left-sided accessory pathway: An uncommon cause of SVT in young people

Concealed left‐sided accessory pathways (CLAP) are a cause of supraventricular tachycardia (SVT) in the young. Most are mapped with right ventricular (RV) apical/outflow pacing. Rarely, alternative means of mapping are required. We review our experience from three pediatric electrophysiology (EP) centers with a rare form of “hidden” CLAP.

Prospective Study of Adenosine on Atrioventricular Nodal Conduction in Pediatric and Young Adult Patients After Heart Transplant

Background: Supraventricular tachycardia is common after heart transplantation. Adenosine, the standard therapy for treating supraventricular tachycardia in children and adults without transplantation, is relatively contraindicated after transplantation because of a presumed risk of prolonged atrioventricular block in denervated hearts. This study tested whether adenosine caused prolonged asystole after transplantation and if it was effective in blocking atrioventricular nodal conduction in these patients. Methods: This was a single-center prospective clinical study including healthy heart transplant recipients 6 months to 25 years of age presenting for routine cardiac catheterization during 2015 to 2016. After catheterization, a transvenous pacing catheter was placed and adenosine was given following a dose-escalation protocol until atrioventricular block was achieved. The incidence of clinically significant asystole (≥12 seconds after adenosine) was quantified. The effects of patient characteristics on adenosine dose required to produce atrioventricular block and duration of effect were also measured. Results: Eighty patients completed adenosine testing. No patient (0%; 95% confidence interval, 0–3) required rescue ventricular pacing. Atrioventricular block was observed in 77 patients (96%; 95% confidence interval, 89–99). The median longest atrioventricular block was 1.9 seconds (interquartile range, 1.4–3.2 seconds), with a mean duration of adenosine effect of 4.3±2.0 seconds. No patient characteristic significantly predicted the adenosine dose to produce atrioventricular block or duration of effect. Results were similar across patient weight categories. Conclusions: Adenosine induces atrioventricular block in healthy pediatric and young adult heart transplant recipients with minimal risk when low initial doses are used (25 &mgr;g/kg; 1.5 mg if ≥60 kg) and therapy is gradually escalated. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02462941.

Cryoablation of Anteroseptal Accessory Pathways with a His Bundle Electrogram on the Ablation Catheter

Background Radiofrequency catheter ablations of anteroseptal (AS) accessory pathways (AP) in pediatric patients have higher incidence of atrioventricular (AV) block than other AP locations. We report our experience using cryoablation in pediatric patients where a His bundle electrogram was noted on the ablation catheter at the site of the successful ablation. Methods and Results We retrospectively reviewed all patients ≤21 years that underwent cryoablation for an AS AP from 2005 to 2012 at our institution (n=70). Patients with a His bundle electrogram noted on the cryoablation catheter at the location of the successful lesion were identified (n=6, 8.5%). All six patients had ventricular preexcitation. Median age of 15.9 years (7.2 - 18.2). AV nodal function was monitored during the cryoablation with intermittent rapid atrial pacing conducted through the AV node (n=2), with atrial extra-stimulus testing (n=2), or during orthodromic reentrant tachycardia (n=2). Acute success occurred in all patients. Two patients had early recurrence of AP conduction. Both patients underwent a second successful cryoablation, again with a His bundle electrogram on the cryoablation catheter. At a median follow-up of 13 months (3 to 37 months) there was no recurrence of accessory pathway conduction and AVN function was normal. Conclusion In a small number of pediatric patients with AS AP with a His bundle electrogram seen on the ablation catheter, the use of cryotherapy was safe and effective for elimination of AP conduction without impairment of AV nodal conduction.

Electrocardiograms in Healthy North American Children in the Digital Age

Background: Interpretation of pediatric ECGs is limited by lack of accurate sex- and race-specific normal reference values obtained with modern technology for all ages. We sought to obtain contemporary digital ECG measurements in healthy children from North America, to evaluate the effects of sex and race, and to compare our results to commonly used published datasets. Methods: Digital ECGs (12-lead) were retrospectively collected for children ⩽18 years old with normal echocardiograms at 19 centers in the Pediatric Heart Network. Patients were classified into 36 groups: 6 age, 2 sex, and 3 race (white, black, and other/mixed) categories. Standard intervals and amplitudes were measured; mean±SD and 2nd/98th percentiles were determined by age group, sex, and race. For each parameter, multivariable analysis, stratified by age, was conducted using sex and race as predictors. Parameters were compared with 2 large pediatric ECG data sets. Results: Among ECGs from 2400 children, significant differences were found by sex and race categories. The corrected QT interval in lead II was greater for girls compared with boys for age groups ≥3 years (P⩽0.03) and for whites compared with blacks for age groups ≥12 years (P<0.05). The R wave amplitude in V6 was greater for boys compared with girls for age groups ≥12 years (P<0.001), for blacks compared with white or other race categories for age groups ≥3 years (P⩽0.006), and greater compared with a commonly used public data set for age groups ≥12 years (P<0.0001). Conclusions: In this large, diverse cohort of healthy children, most ECG intervals and amplitudes varied by sex and race. These differences have important implications for interpreting pediatric ECGs in the modern era when used for diagnosis or screening, including thresholds for left ventricular hypertrophy.