Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients.

Multifocal atrial tachycardia (MAT) has a well-known association with Costello syndrome, but is rarely described with related RAS/MAPK pathway disorders (RASopathies). We report 11 patients with RASopathies (Costello, Noonan, and Noonan syndrome with multiple lentigines [formerly LEOPARD syndrome]) and nonreentrant atrial tachycardias (MAT and ectopic atrial tachycardia) demonstrating overlap in cardiac arrhythmia phenotype. Similar overlap is seen in RASopathies with respect to skeletal, musculoskeletal and cutaneous abnormalities, dysmorphic facial features, and neurodevelopmental deficits. Nonreentrant atrial tachycardias may cause cardiac compromise if sinus rhythm is not restored expeditiously. Typical first-line supraventricular tachycardia anti-arrhythmics (propranolol and digoxin) were generally not effective in restoring or maintaining sinus rhythm in this cohort, while flecainide or amiodarone alone or in concert with propranolol were effective anti-arrhythmic agents for acute and chronic use. Atrial tachycardia resolved in all patients. However, a 4-month-old boy from the cohort was found asystolic (with concurrent cellulitis) and a second patient underwent cardiac transplant for heart failure complicated by recalcitrant atrial arrhythmia. While propranolol alone frequently failed to convert or maintain sinus rhythm, fleccainide or amiodarone, occasionally in combination with propranolol, was effective for RASopathy patient treatment for nonreentrant atrial arrhythmia. Our analysis shows that RASopathy patients may have nonreentrant atrial tachycardia with and without associated cardiac hypertrophy. While nonreentrant arrhythmia has been traditionally associated with Costello syndrome, this work provides an expanded view of RASopathy cardiac arrhythmia phenotype as we demonstrate mutant proteins throughout this signaling pathway can also give rise to ectopic and/or MAT.

Success rates in pediatric WPW ablation are improved with 3-dimensional mapping systems compared with fluoroscopy alone: a multicenter study.

INTRODUCTION: Three-dimensional mapping (3-D) systems are frequently used for ablation of supraventricular tachycardia. Prior studies have demonstrated radiation dosage reduction with 3-D, but there are no data on whether 3-D improves the efficacy of ablation of Wolff-Parkinson-White syndrome (WPW). We sought to determine if 3-D improves the success rate for ablation of WPW in children. METHODS: Multicenter retrospective study including patients ≤21 years of age with WPW undergoing ablation from 2008 to 2012. Success rates using the 2 techniques (3-D vs. fluoroscopy alone [FLUORO]) were compared. RESULTS: Six hundred and fifty-one cases were included (58% male, mean age 13 ± 4 years, 366 [56%] 3-D). Baseline characteristics including gender, weight, accessory pathway (AP) location, number of APs, and repeat ablation attempts were similar between the 2 groups (3-D and FLUORO) The 3-D group was slightly younger (12.7 ± 4.0 vs. 13.3 ± 4.0 years; P = 0.04) and less likely to undergo ablation utilizing cryoenergy (38 [10%] vs. 56 [20%]; P < 0.01). The 3-D group had a higher acute success rate of ablation (355 [97%] vs. 260 [91%]; P < 0.01). No differences were seen in recurrence (16 [5%] vs. 26 [9%]; P = 0.09) or complication rates (1 [0.3%] vs. 1 [0.4%]; P = 0.86) between the groups. On multivariable analysis, 3-D was shown to significantly improve success at ablation with an odds ratio of 3.1 (95% CI 1.44-6.72; P < 0.01). CONCLUSIONS: Use of 3-D significantly improved success rates for ablation of WPW in children. The increase in acute success associated with 3-D suggests it is an important adjunct for catheter ablation of WPW in children.

Loss of ventricular preexcitation during noninvasive testing does not exclude high-risk accessory pathways: A multicenter study of WPW in children.

BACKGROUND: Abrupt loss of ventricular preexcitation on noninvasive evaluation, or nonpersistent preexcitation, in Wolff-Parkinson-White syndrome (WPW) is thought to indicate a low risk of life-threatening events. OBJECTIVE: The purpose of this study was to compare accessory pathway (AP) characteristics and occurrences of sudden cardiac arrest (SCA) and rapidly conducted preexcited atrial fibrillation (RC-AF) in patients with nonpersistent and persistent preexcitation. METHODS: Patients 21 years or younger with WPW and invasive electrophysiology study (EPS) data, SCA, or RC-AF were identified from multicenter databases. Nonpersistent preexcitation was defined as absence/sudden loss of preexcitation on electrocardiogram, Holter monitoring, or exercise stress test. RC-AF was defined as clinical preexcited atrial fibrillation with shortest preexcited R-R interval (SPERRI) ≤ 250 ms. AP effective refractory period (APERP), SPERRI at EPS , and shortest preexcited paced cycle length (SPPCL) were collected. High-risk APs were defined as APERP, SPERRI, or SPPCL ≤ 250 ms. RESULTS: Of 1589 patients, 244 (15%) had nonpersistent preexcitation and 1345 (85%) had persistent preexcitation. There were no differences in sex (58% vs 60% male; P=.49) or age (13.3±3.6 years vs 13.1±3.9 years; P=.43) between groups. Although APERP (344±76 ms vs 312±61 ms; P<.001) and SPPCL (394±123 ms vs 317±82 ms; P<.001) were longer in nonpersistent vs persistent preexcitation, there was no difference in SPERRI at EPS (331±71 ms vs 316±73 ms; P=.15). Nonpersistent preexcitation was associated with fewer high-risk APs (13% vs 23%; P<.001) than persistent preexcitation. Of 61 patients with SCA or RC-AF, 6 (10%) had nonpersistent preexcitation (3 SCA, 3 RC-AF). CONCLUSION: Nonpersistent preexcitation was associated with fewer high-risk APs, though it did not exclude the risk of SCA or RC-AF in children with WPW.

Polymorphic ventricular tachycardia and KCNJ2 mutations.

We sought to identify the electrophysiologic basis of life-threatening events associated with polymorphic ventricular tachycardia (PVT) in young patients with heterozygous KCNJ2 mutations. PVT describes a beat-to-beat alternating QRS axis and morphology during ventricular tachycardia. PVT may be well tolerated and even asymptomatic in young patients without other heart disease, but an association with syncope, cardiac arrest, or sudden death has long been known. Little is known of the basis of life-threatening events associated with PVT in this setting. We identified heterozygous KCNJ2 mutations (R67W and C101R respectively) in 2 adolescents with PVT (cycle length > 375 ms, < 160 beats/minute). Biophysical properties of wild-type and mutant KCNJ2 channels were characterized during heterologous expression in Xenopus oocytes. Despite a large tachycardia burden, neither patient experienced symptoms during electrocardiographic documentation of PVT. One patient had a history of cardiac arrest, but neither had other evidence of heart disease. Both patients were treated with an implantable cardioverter-defibrillator (ICD). In one patient, ICD interrogation identified rapid ventricular tachycardia (cycle length of 190 to 270 ms), terminated with a single 29-J asynchronous shock, as the cause of 2 syncopal episodes occurring 19 months apart. Biophysical characterization of KCNJ2-C101R demonstrated a loss-of-function and a dominant-negative effect on Kir2.1. Similar effects were previously observed for KCNJ2-R67W. Heterozygous mutations in KCNJ2 can cause life-threatening ventricular arrhythmias. Arrhythmia documented during cardiac arrest is rapid ventricular tachycardia; ICD is effective therapy for cardiac arrest in patients with PVT due to KCNJ2 mutation.

The pharmacokinetics of esmolol in pediatric subjects with supraventricular arrhythmias.

Esmolol is often used in the acute management of children with arrhythmias and/or hypertension; however, pharmacokinetic studies of the drug in children have been limited. The objective of this study was to determine the pharmacokinetics of esmolol in children with a history of supraventricular arrhythmias (SVT) who were scheduled for diagnostic electrophysiology study or a catheter ablation procedure. Subjects were stratified into two age groups: 2-11 and 12-16 years. After an episode of stimulated or spontaneous SVT, esmolol was administered intravenously as a 1,000 microg/kg bolus followed by continuous infusion at 300 microg/kg/min. Blood samples were collected before, at 5, 10 and 15 min after the loading dose, and 3, 6, 9, 12, 15 and 20 min after the end of the infusion. Plasma concentration of esmolol was quantitated by a specific LC/MS assay. Pharmacokinetic data were available for 25 subjects. Arterial esmolol concentrations were approximately five times greater than venous concentrations. Esmolol had an extremely short distribution half-life (0.6 min), a rapid terminal elimination half-life (6.9 min), and a rapid clearance (119 +/- 51 mL/min/kg) which was not related to subject age or weight. Seventeen of the subjects (63%) converted to normal sinus rhythm in an average of 2 min (range 0-5 min). The pharmacokinetics of esmolol and its efficacy in terminating SVT in children is similar to that observed in adults.

A view from down under: laparoscopic look at a subrectus pacemaker.

This article describes an infant with multiple congenital anomalies who underwent laparoscopic insertion of a gastrostomy tube. Prior repair of congenital heart defects had resulted in complete heart block necessitating the implantation of an epicardial pacemaker. A photograph taken within the peritoneal cavity provides a unique view of the patient's subrectus pulse generator.

Circadian and seasonal variation of malignant arrhythmias in a pediatric and congenital heart disease population.

INTRODUCTION: Recent studies in adult populations have revealed seasonal variation in the frequency of acute cardiovascular events, including life-threatening arrhythmias, demonstrating increased events during winter and early spring. Trends in the time of day that arrhythmias occur also were noted. We sought to establish whether pediatric and young adult congenital heart disease implantable cardioverter defibrillator (ICD) recipients have circadian or seasonal variability in shock frequency, similar to adult populations. METHODS AND RESULTS: Data from ICD patients at six pediatric centers in North America were analyzed to assess the timing of life-threatening arrhythmias. The populations consisted of children and adults with congenital heart disease and ICDs placed for malignant arrhythmias. Data were considered in 46 patients who received appropriate therapy (total 139 episodes) for ventricular tachycardia or ventricular fibrillation. Multiple variables were analyzed, including time of day, day of week, and month of year. In contrast to previously studied adult patients, fewer events occurred in the early morning (7.5%), with the most therapies occurring between 6 P.M. and midnight (35%). An increased frequency of therapies was observed in the fall and winter (September-January), representing 60% of all appropriate shocks. Unlike adult populations, Mondays did not have an increased frequency of malignant arrhythmias. CONCLUSION: Pediatric and adult congenital heart disease populations have moderate seasonal and 24-hour variation in ICD event rate, with some distinctly different peaks than those seen in typical adult ICD populations. These findings suggest circadian variation in arrhythmia vulnerability that may differ from conventional occupational, physical, or emotional stressors. (J Cardiovasc Electrophysiol, Vol. 13, pp.