Anne Dubin

All Publications

Electrocardiographic repolarization abnormalities and increased risk of life-threatening arrhythmias in children with dilated cardiomyopathy HEART RHYTHM Chen, S., Motonaga, K. S., Hollander, S. A., Almond, C. S., Rosenthal, D. N., Kaufman, B. D., May, L. J., Avasarala, K., Dao, D. T., Dubin, A. M., Ceresnak, S. R. 2016; 13 (6): 1289-1296
Abstract

Life-threatening arrhythmia events (LTEs) occur in ~5% of children with dilated cardiomyopathy (DCM). While prolonged QRS duration has been shown to be associated with LTEs, electrocardiographic (ECG) repolarization findings have not been examined.We sought to determine the associations between ECG repolarization abnormalities and LTEs in children with DCM.A single-center retrospective review of children with DCM was performed. LTEs were defined as documented ventricular tachycardia or fibrillation requiring medical intervention. Three pediatric cardiologists, blinded to clinical events, evaluated ECGs obtained at the time of initial referral. Kaplan-Meier survival and Cox proportional hazards analyses were used to evaluate time to LTEs.A total of 137 patients (mean age 7.8 ± 6.7 years; 75(55%) male patients) with DCM (mean ejection fraction 35% ± 16%) were included; 67 patients (49%) had a corrected JT (JTc) interval of ≥340 ms, 72 (53%) had a corrected QT (QTc) interval of ≥450 ms, and 41 (30%) had abnormal T waves. LTEs occurred in 15 patients at a median of 12 months (interquartile range 3-36 months) after the initial ECG. Patients with LTEs had a longer JTc interval (371 ± 77 ms vs 342 ± 41 ms; P = .02) and a longer QTc interval (488 ± 96 ms vs 453 ± 44 ms; P = .01). In survival analysis, a JTc interval of ≥390 ms (hazard ratio [HR] 4.07; 95% confidence interval [CI] 1.12-14.83; P = .03), a QTc interval of ≥510 ms (HR 6.95; 95% CI 1.53-31.49; P = .01), abnormal T-wave inversion (HR 11.62; 95% CI 2.75-49.00; P = .001), and ST-segment depression (HR 6.91; 95% CI 1.25-38.27; P = .03) were associated with an increased risk of LTEs, even after adjusting for QRS duration and amiodarone use.Repolarization abnormalities are common in children with DCM. Certain ECG repolarization abnormalities, such as significantly prolonged JTc and QTc intervals, may be useful in identifying patients at risk of LTEs.

View details for DOI 10.1016/j.hrthm.2016.02.014

View details for Web of Science ID 000376334800016

View details for PubMedID 26945851
The precise timing of tachycardia entrainment is determined by the postpacing interval, the tachycardia cycle length, and the pacing rate: Theoretical insights and practical applications HEART RHYTHM Kaiser, D. W., Hsia, H. H., Dubin, A. M., Liem, L. B., Viswanathan, M. N., Zei, P. C., Wang, P. J., Narayan, S. M., Turakhia, M. P. 2016; 13 (3): 695-703
View details for DOI 10.1016/j.hrthm.2015.11.032

View details for Web of Science ID 000372367800012
The precise timing of tachycardia entrainment is determined by the postpacing interval, the tachycardia cycle length, and the pacing rate: Theoretical insights and practical applications. Heart rhythm Kaiser, D. W., Hsia, H. H., Dubin, A. M., Liem, L. B., Viswanathan, M. N., Zei, P. C., Wang, P. J., Narayan, S. M., Turakhia, M. P. 2016; 13 (3): 695-703
Abstract

Previous observations have reported that the number of pacing stimuli required to entrain a tachycardia varies on the basis of arrhythmia type and location, but a quantitative formulation of the number needed to entrain (NNE) that unifies these observations has not been characterized.We sought to investigate the relationship between the number of pacing stimulations, the tachycardia cycle length (TCL), the overdrive pacing cycle length (PCL), and the postpacing interval (PPI) to accurately estimate the timing of tachycardia entrainment.First, we detailed a mathematical derivation unifying electrophysiological parameters with empirical confirmation in 2 patients undergoing catheter ablation of typical atrial flutter. Second, we validated our formula in 44 patients who underwent various catheter ablation procedures. For accuracy, we corrected for rate-related changes in conduction velocity.We derived the equations NNE = |(PPI - TCL)/(TCL - PCL)| + 1 and Tachycardia advancement = (NNE - 1) × (TCL - PCL) - (PPI - TCL), which state that the NNE and the amount of tachycardia advancement on the first resetting stimulation are determined using regularly measured intracardiac parameters. In the retrospective cohort, the observed PPI - TCL highly correlated with the predicted PPI - TCL (mean difference 5.8 ms; r = 0.97; P < .001), calculated as PPI - TCL = (NNE - 1) × (TCL - PCL) - tachycardia advancement.The number of pacing stimulations required to entrain a reentrant tachycardia is predictable at any PCL after correcting for cycle length-dependent changes in conduction velocity. This relationship unifies established empirically derived diagnostic and mapping criteria for supraventricular tachycardia and ventricular tachycardia. This relationship may help elucidate when antitachycardia pacing episodes are ineffective or proarrhythmic and could potentially serve as a theoretical basis to customize antitachycardia pacing settings for improved safety and effectiveness.

View details for DOI 10.1016/j.hrthm.2015.11.032

View details for PubMedID 26611239
Evaluation and management of bradycardia in neonates and children EUROPEAN JOURNAL OF PEDIATRICS Baruteau, A., Perry, J. C., Sanatani, S., Horie, M., Dubin, A. M. 2016; 175 (2): 151-161
Abstract

Heart rate is commonly used in pediatric early warning scores. Age-related changes in the anatomy and physiology of infants and children produce normal ranges for electrocardiogram features that differ from adults and vary with age. Bradycardia is defined as a heart rate below the lowest normal value for age. Pediatric bradycardia most commonly manifests as sinus bradycardia, junctional bradycardia, or atrioventricular block. As a result of several different etiologies, it may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited sinus node dysfunction or progressive cardiac conduction disorders. Management and eventual prognosis of bradycardia in the young are entirely dependent upon the underlying cause. Reasons to intervene for bradycardia are the association of related symptoms and/or the downstream risk of heart failure or pause-dependent tachyarrhythmia. The simplest aspect of severe bradycardia management is reflected in the Pediatric and Advanced Life Support (PALS) guidelines.Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current practice for evaluation and management of bradycardia in neonates and children.• Bradycardia is defined as a heart rate below the lowest normal value for age. Age related changes in the anatomy and physiology of infants and children produce normal ranges for electrocardiogram features that differ from adults and vary with age. • Pediatric bradycardia most commonly manifests as sinus bradycardia, junctional bradycardia, or atrioventricular block. What is New: • Management and eventual prognosis of bradycardia in the young are entirely dependent upon the underlying cause. Bradycardia may occur in a structurally normal heart or in association with congenital heart disease. Genetic variants in multiple genes have been described. • Reasons to intervene for bradycardia are the association of related symptoms and/or the downstream risk of heart failure or pause-dependent tachyarrhythmia. Early diagnosis and appropriate management are critical in order to prevent sudden death.

View details for DOI 10.1007/s00431-015-2689-z

View details for Web of Science ID 000368808600001

View details for PubMedID 26780751
A Pilot Study Assessing ECG versus ECHO Ventriculoventricular Optimization in Pediatric Resynchronization Patients. Journal of cardiovascular electrophysiology Punn, R., Hanisch, D., Motonaga, K. S., Rosenthal, D. N., Ceresnak, S. R., Dubin, A. M. 2016; 27 (2): 210-216
Abstract

Cardiac resynchronization therapy indications and management are well described in adults. Echocardiography (ECHO) has been used to optimize mechanical synchrony in these patients; however, there are issues with reproducibility and time intensity. Pediatric patients add challenges, with diverse substrates and limited capacity for cooperation. Electrocardiographic (ECG) methods to assess electrical synchrony are expeditious but have not been extensively studied in children. We sought to compare ECHO and ECG CRT optimization in children.Prospective, pediatric, single-center cross-over trial comparing ECHO and ECG optimization with CRT. Patients were assigned to undergo either ECHO or ECG optimization, followed for 6 months, and crossed-over to the other assignment for another 6 months. ECHO pulsed-wave tissue Doppler and 12-lead ECG were obtained for 5 VV delays. ECG optimization was defined as the shortest QRSD and ECHO optimization as the lowest dyssynchrony index. ECHOs/ECGs were interpreted by readers blinded to optimization technique. After each 6 month period, these data were collected: ejection fraction, velocimetry-derived cardiac index, quality of life, ECHO-derived stroke distance, M-mode dyssynchrony, study cost, and time. Outcomes for each optimization method were compared.From June 2012 to December 2013, 19 patients enrolled. Mean age was 9.1 ± 4.3 years; 14 (74%) had structural heart disease. The mean time for optimization was shorter using ECG than ECHO (9 ± 1 min vs. 68 ± 13 min, P < 0.01). Mean cost for charges was $4,400 ± 700 less for ECG. No other outcome differed between groups.ECHO optimization of synchrony was not superior to ECG optimization in this pilot study. ECG optimization required less time and cost than ECHO optimization.

View details for DOI 10.1111/jce.12863

View details for PubMedID 26515428
Screening ECGs for young competitive athletes: it is complicated CURRENT OPINION IN PEDIATRICS Dubin, A. M. 2015; 27 (5): 604-608
Abstract

The role of the ECG in preparticipation sports screening for adolescent athletes is a major area of controversy today. Sudden cardiac death, especially in a young seemingly healthy individual, is a tragic and highly publicized event, which is often surrounded by cries from the public and medical community to 'do something.'This emotional need to address these catastrophic events has led to over 4000 articles addressing the optimal way to screen the young athlete, as well as conflicting recommendations from the American Heart Association and the European Society of Cardiology, specifically in regards to inclusion of a screening ECG. This article will review the advances in the field over the last year, including the new guidelines on screening of the young athlete from the American Heart Association.This last year has seen several important additions to the controversy surrounding the use of the 12-lead ECG in the screening of the young athlete. Although improved ECG criteria have decreased the prevalence of false positives, the actual utility of this practice has not been tested in real clinical practice outside of a formal investigation.

View details for DOI 10.1097/MOP.0000000000000261

View details for Web of Science ID 000369436000010

View details for PubMedID 26165628
Task Force 4: Pediatric Cardiology Fellowship Training in Electrophysiology. SPCTPD/ACC/AAP/AHA. Circulation Dubin, A. M., Walsh, E. P., Franklin, W., Kanter, R. J., Saul, J. P., Shah, M. J., Van Hare, G. F., Vincent, J. A. 2015; 132 (6): e75-80
View details for DOI 10.1161/CIR.0000000000000195

View details for PubMedID 25769637
Task Force 4: Pediatric Cardiology Fellowship Training in Electrophysiology CIRCULATION Dubin, A. M., Walsh, E. P., Franklin, W., Kanter, R. J., Saul, J. P., Shah, M. J., Van Hare, G. F., Vincent, J. A. 2015; 132 (6): E75-E80
View details for DOI 10.1161/CIR.0000000000000195

View details for Web of Science ID 000359666700007
Task Force 4: Pediatric Cardiology Fellowship Training in Electrophysiology JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Dubin, A. M., Walsh, E. P., Franklin, W., Kanter, R. J., Saul, J. P., Shah, M. J., Van Hare, G. F., Vincent, J. A. 2015; 66 (6): 706-711
View details for DOI 10.1016/j.jacc.2015.03.005

View details for Web of Science ID 000359139600015
Task Force 4: Pediatric Cardiology Fellowship Training in Electrophysiology. Journal of the American College of Cardiology Dubin, A. M., Walsh, E. P., Franklin, W., Kanter, R. J., Saul, J. P., Shah, M. J., Van Hare, G. F., Vincent, J. A. 2015; 66 (6): 706-711
View details for DOI 10.1016/j.jacc.2015.03.005

View details for PubMedID 25777633
50 is the new 70: Short ventriculoatrial times are common in children with atrioventricular reciprocating tachycardia HEART RHYTHM Ceresnak, S. R., Doan, L. N., Motonaga, K. S., Avasarala, K., Trela, A. V., Reddy, C. D., Dubin, A. M. 2015; 12 (7): 1541-1547
Abstract

One of the basic electrophysiological principles of atrioventricular reciprocating tachycardia (AVRT) is that ventriculoatrial (VA) times during tachycardia are >70 ms. We hypothesized, however, that children may commonly have VA times <70 ms in AVRT.This study sought to determine the incidence and characteristics associated with short-VA AVRT in children.A retrospective single-center review of children with AVRT from 2000 to 2014 was performed. All patients ≤18 years of age with AVRT at electrophysiology study were included. Patients with persistent junctional reciprocating tachycardia, atrioventricular nodal reentry tachycardia, and tachycardia not unequivocally proven to be AVRT were excluded. VA time was defined as the time between earliest ventricular activation and earliest atrial activation in any lead and was confirmed by 2 electrophysiologists. Patients with VA times <70 ms (SHORT-VA) and those with standard VA times ≥70 ms (STD-VA) were compared. Logistic regression analysis identified characteristics of SHORT-VA patients.A total of 495 patients with AVRT were included (mean age 11.7 ± 4.1 years). There were 265 patients (54%) with concealed accessory pathways (APs) and 230 (46%) with Wolff-Parkinson-White syndrome. AP location was left-sided in 301 patients (61%) and right-sided in 194 (39%). The mean VA time in AVRT was 100 ± 33 ms. A total of 63 patients (13%) had VA times <70 ms (SHORT-VA). The shortest VA time during AVRT was 50 ms. There was no difference in age, AV nodal block cycle, or body surface area between SHORT-VA and STD-VA patients, but SHORT-VA patients had lower weight (43 ± 17 vs 51 ± 23 kg, P = .02), lower AV nodal effective refractory period (AVNERP; 269 ± 50 vs 245 ± 52 ms, P < .01), and more left-sided APs (50 [79%] vs 251 [58%]; P < .01]. On multivariate logistic regression, factors associated with SHORT-VA included left-sided AP (odds ratio [OR] 5.79, confidence interval [95% CI] 2.21-15.1, P < .01), shorter AVNERP (OR 0.99, CI 0.98-0.99, P < .01), and lower weight (OR 0.97, CI 0.95-0.99, P < .01).Children with AVRT can frequently have VA times <70 ms, with 50 ms being the shortest VA time. This finding debunks the classic electrophysiology principle that VA times in AVRT must be >70 ms. SHORT-VA AVRT was more common in children with left-sided APs.

View details for DOI 10.1016/j.hrthm.2015.03.047

View details for Web of Science ID 000356766500028
Success Rates in Pediatric WPW Ablation Are Improved with 3-Dimensional Mapping Systems Compared with Fluoroscopy Alone: A Multicenter Study JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Ceresnak, S. R., Dubin, A. M., Kim, J. J., Valdes, S. O., Fishberger, S. B., Shetty, I., Zimmerman, F., Tanel, R. E., Epstein, M. R., Motonaga, K. S., Capone, C. A., Nappo, L., Gates, G. J., Pass, R. H. 2015; 26 (4): 412-416
Abstract

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.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.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).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.

View details for DOI 10.1111/jce.12623

View details for Web of Science ID 000352814300012
Diminished exercise capacity and chronotropic incompetence in pediatric patients with congenital complete heart block and chronic right ventricular pacing HEART RHYTHM Motonaga, K. S., Punn, R., Axelrod, D. M., Ceresnak, S. R., Hanisch, D., Kazmucha, J. A., Dubin, A. M. 2015; 12 (3): 560-565
Abstract

Chronic right ventricular (RV) pacing has been associated with decreased exercise capacity and left ventricular (LV) function in adults with congenital complete atrioventricular block (CCAVB), but not in children.The purpose of this study was to evaluate the exercise capacity and LV function in pediatric patients with CCAVB receiving chronic RV pacing.We prospectively evaluated pediatric patients with isolated CCAVB receiving atrial synchronous RV pacing for at least 5 years. Supine bicycle ergometry was performed, and LV ejection fraction (EF) was evaluated by echocardiography.Ten CCAVB subjects and 31 controls were matched for age, gender, and body surface area. CCAVB subjects had normal resting EF (63.1% ± 4.0%) and had been paced for 7.9 ± 1.4 years. Exercise testing demonstrated reduced functional capacity in CCAVB patients compared to controls with a lower VO2peak (26.0 ± 6.6 mL/kg/min vs 39.9 ± 7.0 mL/kg/min, P <.001), anaerobic threshold (15.6 ± 3.9 mL/kg/min vs 18.8 ± 2.7 mL/kg/min, P = .007), and oxygen uptake efficiency slope (1210 ± 406 vs 1841 ± 452, P <.001). Maximum heart rate (165 ± 8 bpm vs 185 ± 9 bpm, P <.001) and systolic blood pressure (159 ± 17 mm Hg vs 185 ± 12 mm Hg, P <.019) also were reduced in CCAVB patients despite maximal effort (respiratory exchange ratio 1.2 ± 0.1). EF was augmented with exercise in controls but not in CCAVB patients (13.2% ± 9.3% vs 0.2% ± 4.8% increase, P <.001).Clinically asymptomatic children with chronic RV pacing due to CCAVB have significant reductions in functional capacity accompanied by chronotropic incompetence and inability to augment EF with exercise.

View details for DOI 10.1016/j.hrthm.2014.11.036

View details for Web of Science ID 000349966100018

View details for PubMedID 25433143
Ventricular lead redundancy to prevent cardiovascular events and sudden death from lead fracture in pacemaker-dependent children HEART RHYTHM Ceresnak, S. R., Perera, J. L., Motonaga, K. S., Avasarala, K., Malloy-Walton, L., Hanisch, D., Punn, R., Maeda, K., Reddy, V. M., Doan, L. N., Kirby, K., Dubin, A. M. 2015; 12 (1): 111-116
Abstract

Children requiring a permanent epicardial pacemaker(PM) traditionally have a single lead placed on the right ventricle. Lead failure in pacemaker dependent(PMD) children, however, can result in cardiovascular events(CVE) and death.To determine if redundant ventricular lead systems(RVLS) can safeguard against CVE and death in PMD children.Single-center study of PMD patients undergoing placement of RVLS from 2002-2013. Patients ≤ 21 years of age who were PMD were included. Patients with biventricular systems(BiV) systems placed for standard resynchronization indications were excluded. RVLS patients were compared to PMD patients with only a single pacing lead on the ventricle(SiV).769 patients underwent PM/ICD placement with 76 BiV implants and there were 49 PMD patients(6%). 13 patients underwent implantation of a RVLS. There was no difference between the RVLS group(n=13) and SiV PMD control group(n=24) with regard to age(RVLS 9.5±5.8 vs. SiV 9.4±6.7 years; p=0.52), weight(RVLS 38.2±32.6 vs. SiV 35.2±29.3 kg; p=0.62), indication for pacing, procedural complications or time to follow-up. There were 2 lead fractures (17%) in the RVLS group(mean follow-up 3.8±2.9 years) with no deaths or presentations with CVE. The SiV control group had 3 lead fractures (13%)(mean follow-up 2.8±2.9 years), with no deaths, but all 3 patients presented with CVE and required emergent PM placement.RVLS systems should be considered in children who are PMD and require permanent epicardial pacing. BiV pacing and RVLS may decrease the risk of CVEs in the event of lead failure in PMD patients.

View details for DOI 10.1016/j.hrthm2014.09.056

View details for Web of Science ID 000346857100022
PACES/HRS Expert Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease: Executive Summary HEART RHYTHM Khairy, P., Van Hare, G. F., Balaji, S., Berul, C. I., Cecchin, F., Cohen, M. I., Daniels, C. J., Deal, B. J., Dearani, J. A., de Groot, N., Dubin, A. M., Harris, L., Janousek, J., Kanter, R. J., Karpawich, P. P., Perry, J. C., Seslar, S. P., Shah, M. J., Silka, M. J., Triedman, J. K., Walsh, E. P., Warnes, C. A. 2014; 11 (10): E81-E101
View details for DOI 10.1016/j.hrthm.2014.0.5.008

View details for Web of Science ID 000343112200003
PACES/HRS Expert Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease: developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American College of Cardiology (ACC), the American Heart Association (AHA), the European Heart Rhythm Association (EHRA), the Canadian Heart Rhythm Society (CHRS), and the International Society for Adult Congenital Heart Disease (ISACHD). Heart rhythm Khairy, P., Van Hare, G. F., Balaji, S., Berul, C. I., Cecchin, F., Cohen, M. I., Daniels, C. J., Deal, B. J., Dearani, J. A., Groot, N. d., Dubin, A. M., Harris, L., Janousek, J., Kanter, R. J., Karpawich, P. P., Perry, J. C., Seslar, S. P., Shah, M. J., Silka, M. J., Triedman, J. K., Walsh, E. P., Warnes, C. A. 2014; 11 (10): e102-65
View details for DOI 10.1016/j.hrthm.2014.05.009

View details for PubMedID 24814377
PACES/HRS Expert Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease HEART RHYTHM Khairy, P., Van Hare, G. F., Balaji, S., Berul, C. I., Cecchin, F., Cohen, M. I., Daniels, C. J., Deal, B. J., Dearani, J. A., de Groot, N., Dubin, A. M., Harris, L., Janousek, J., Kanter, R. J., Karpawich, P. P., Perry, J. C., Seslar, S. P., Shah, M. J., Silka, M. J., Triedman, J. K., Walsh, E. P., Warnes, C. A. 2014; 11 (10): E102-E165
View details for DOI 10.1016/j.hrthm.2014.0.5.009

View details for Web of Science ID 000343112200004
Molecular diagnosis of long QT syndrome at 10 days of life by rapid whole genome sequencing. Heart rhythm Priest, J. R., Ceresnak, S. R., Dewey, F. E., Malloy-Walton, L. E., Dunn, K., Grove, M. E., Perez, M. V., Maeda, K., Dubin, A. M., Ashley, E. A. 2014; 11 (10): 1707-1713
Abstract

The advent of clinical next generation sequencing is rapidly changing the landscape of rare disease medicine. Molecular diagnosis of long QT syndrome (LQTS) can impact clinical management, including risk stratification and selection of pharmacotherapy based on the type of ion channel affected, but results from current gene panel testing requires 4 to 16 weeks before return to clinicians.A term female infant presented with 2:1 atrioventricular block and ventricular arrhythmias consistent with perinatal LQTS, requiring aggressive treatment including epicardial pacemaker, and cardioverter-defibrillator implantation and sympathectomy on day of life two. We sought to provide a rapid molecular diagnosis for optimization of treatment strategies.We performed CLIA-certified rapid whole genome sequencing (WGS) with a speed-optimized bioinformatics platform to achieve molecular diagnosis at 10 days of life.We detected a known pathogenic variant in KCNH2 that was demonstrated to be paternally inherited by followup genotyping. The unbiased assessment of the entire catalog of human genes provided by whole genome sequencing revealed a maternally inherited variant of unknown significance in a novel gene.Rapid clinical WGS provides faster and more comprehensive diagnostic information by 10 days of life than standard gene-panel testing. In selected clinical scenarios such as perinatal LQTS, rapid WGS may be able to provide more timely and clinically actionable information than a standard commercial test.

View details for DOI 10.1016/j.hrthm.2014.06.030

View details for PubMedID 24973560
Molecular diagnosis of long QT syndrome at 10 days of life by rapid whole genome sequencing HEART RHYTHM Priest, J. R., Ceresnak, S. R., Dewey, F. E., Malloy-Walton, L. E., Dunn, K., Grove, M. E., Perez, M. V., Maeda, K., Dubin, A. M., Ashley, E. A. 2014; 11 (10): 1707-1713
View details for DOI 10.1016/j.hrthm.20l4.06.030

View details for Web of Science ID 000343112200012
PACES/HRS Expert Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease CANADIAN JOURNAL OF CARDIOLOGY Khairy, P., Van Hare, G. F., Balaji, S., Berul, C. I., Cecchin, F., Cohen, M. I., Daniels, C. J., Deal, B. J., Dearani, J. A., de Groot, N., Dubin, A. M., Harris, L., Janousek, J., Kanter, R. J., Karpawich, P. P., Perry, J. C., Seslar, S. P., Shah, M. J., Silka, M. J., Triedman, J. K., Walsh, E. P., Warnes, C. A. 2014; 30 (10): E1-E63
View details for DOI 10.1016/j.cjca.2014.09.002

View details for Web of Science ID 000343330000002
The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary. [Corrected]. journal of heart and lung transplantation Kirk, R., Dipchand, A. I., Rosenthal, D. N., Addonizio, L., Burch, M., Chrisant, M., Dubin, A., Everitt, M., Gajarski, R., Mertens, L., Miyamoto, S., Morales, D., Pahl, E., Shaddy, R., Towbin, J., Weintraub, R. 2014; 33 (9): 888-909
View details for DOI 10.1016/j.healun.2014.06.002

View details for PubMedID 25110323
Assessment of intrathoracic impedance algorithm in the pediatric and adult congenital population. Pacing and clinical electrophysiology : PACE Silva, J. N., Von Bergen, N. H., Dubin, A. M., Collins, K. K., Chen, J., Bowman, T. M., Van Hare, G. F. 2014; 37 (9): 1174-1180
Abstract

Decreased intrathoracic impedance has been used in adults to predict heart failure (HF) exacerbations. A commercial algorithm, OptiVol® (Medtronic Inc., Minneapolis, MN, USA), identifies patients with decreased impedance. We sought to determine the specificity, sensitivity, and positive predictive value (PPV) of OptiVol for predicting HF exacerbation or increased arrhythmia burden in pediatric and adult congenital heart disease (CHD) patients.A multicenter retrospective chart review was undertaken. Inclusion criteria were: (1) <19 years or CHD adults, (2) an implanted device with OptiVol capability, (3) implanted between April 9 and September 6, and (4) follow-up of >30 days postimplant. Clinical events were defined as clinical HF exacerbation/hospital admission, initiation/uptitration of medication, or increased arrhythmia burden.Seventy-two patients (19 ± 9 years) were identified with the following indications: 20% dilated cardiomyopathy (DCM), 11% hypertrophic cardiomyopathy (HCM), 43% CHD, 15% channelopathy, and 11% other. Thirty-nine had 122 OptiVol crossings (median 2, range 1-11); 30% were linked to a cause. The remaining 33 had no crossing, though 17 had 89 clinical events. The clinical event rate was 19% greater in patients with crossings, though not statistically significant (P = 0.4). The algorithm had a 59% sensitivity, 52% specificity, and 62% PPV. Clinical HF exacerbation and arrhythmia burden did not significantly correlate with decreased impedance though uptitration or initiation of HF medication did correlate significantly (P = 0.03).The algorithm sensitivity for pediatric DCM, HCM, CHD, and adult CHD was equivalent to the general adult population. Further studies are warranted to assess whether inaccuracy in prediction is secondary to the algorithm or to differences in the clinical response of pediatric/CHD patients.

View details for DOI 10.1111/pace.12372

View details for PubMedID 24646399
Assessment of Intrathoracic Impedance Algorithm in the Pediatric and Adult Congenital Population PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Silva, J. N., Von Bergen, N. H., Dubin, A. M., Collins, K. K., Chen, J., Bowman, T. M., Van Hare, G. F. 2014; 37 (9): 1174-1180
View details for DOI 10.1111/pace.12372

View details for Web of Science ID 000342833000014
PACES/HRS Expert Consensus Statement on the Evaluation and Management of Ventricular Arrhythmias in the Child With a Structurally Normal Heart HEART RHYTHM Crosson, J. E., Callans, D. J., Bradley, D. J., Dubin, A., Epstein, M., Etheridge, S., Papez, A., Phillips, J. R., Rhodes, L. A., Saul, P., Stephenson, E., Stevenson, W., Zimmerman, F. 2014; 11 (9): E55-E78
View details for DOI 10.1016/j.hrthm.2014.05.010

View details for Web of Science ID 000341484500005

View details for PubMedID 24814375
Cardiac Resynchronization Therapy for Pediatric Patients With Heart Failure and Congenital Heart Disease A Reappraisal of Results CIRCULATION Motonaga, K. S., Dubin, A. M. 2014; 129 (18): 1879-1891
View details for DOI 10.1161/CIRCULATIONAHA.113.001383

View details for Web of Science ID 000335367500016
Incidence and Risk Factors of Complete Atrioventricular Block after Operative Ventricular Septal Defect Repair CONGENITAL HEART DISEASE Siehr, S. L., Hanley, F. L., Reddy, V. M., Miyake, C. Y., Dubin, A. M. 2014; 9 (3): 211-215
Abstract

BACKGROUND: Complete atrioventricular block (AVB) is a recognized complication of ventricular septal defect (VSD) repair. The objective of this study was to examine incidence and risk factors. METHODS: This is a single-center, retrospective study. All pediatric patients (age <18 years) who underwent VSD repair between November 2001 and August 2009 with concordant atrioventricular and ventriculoarterial connections were included. Patients were classified as having no AVB or transient AVB, and outcomes of early pacemaker placement (before hospital discharge) or late pacemaker placement (after hospital discharge) were recorded. RESULTS: Eight hundred twenty-eight patients (48.6% female) underwent VSD repair during the study period. Mean age at repair was 14 ± 29.4 months. A total of 64 patients (7.7%) developed surgical AVB. Among those patients who developed AVB, 48 (75%) had transient AVB. Sixteen patients (1.9%) required a pacemaker, 14 early (88%) and 2 late (12%). Patients <4 kg (4.2% vs. 1%, P ≤ .01) and those with inlet VSDs (11.6% vs. 1.4%, P ≤ .01) were more likely to develop surgical AVB. Surgical AVB was not influenced by the presence of chromosomal abnormalities or other congenital heart disease. CONCLUSION: The overall incidence of surgical AVB is consistent with previous reports. Weight <4 kg and presence of an inlet VSD were significant risk factors.

View details for DOI 10.1111/chd.12110

View details for Web of Science ID 000337721700012
Diagnosis and Management of Pediatric Brugada Syndrome: A Survey of Pediatric Electrophysiologists PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Harris, B. U., Miyake, C. Y., Motonaga, K. S., Dubin, A. M. 2014; 37 (5): 638-642
Abstract

Brugada syndrome (BrS) can be difficult to diagnose and treat, especially in the young patient. As there is currently no consensus on the evaluation and treatment of BrS in the pediatric population, we sought to describe the current practice for the diagnosis and treatment of BrS among pediatric electrophysiologists.A web-based survey was distributed to 204 physician members (MDs) of The Pediatric and Adult Congenital Electrophysiology Society (PACES). Practice characteristics, BrS patient attributes, and diagnostic and therapeutic preferences were collected.Responses were obtained from 83 pediatric electrophysiologists. The most common initial presentation was family history. There is a large variation in testing, particularly in the use of electrophysiology (EP) studies, drug challenge testing, and genetic testing. Despite limited treatment options, there is only consensus in the therapeutic approach to the pediatric patient with symptomatic BrS with 97% of physicians recommending an implantable cardioverter defibrillator (ICD). In the asymptomatic patient, a wide variation in therapy was seen with only 27% of physicians recommending an ICD CONCLUSIONS: Significant practice variation exists among pediatric electrophysiologists with deviation from accepted diagnostic and therapeutic practices for adult BrS patients. Further studies are necessary to establish best practice guidelines for BrS in the pediatric EP community.

View details for DOI 10.1111/pace.12346

View details for Web of Science ID 000334863000016
In-Hospital Arrhythmia Development and Outcomes in Pediatric Patients With Acute Myocarditis AMERICAN JOURNAL OF CARDIOLOGY Miyake, C. Y., Teele, S. A., Chen, L., Motonaga, K. S., Dubin, A. M., Balasubramanian, S., Balise, R. R., Rosenthal, D. N., Alexander, M. E., Walsh, E. P., Mah, D. Y. 2014; 113 (3): 535-540
Abstract

Cardiac arrhythmias are a complication of myocarditis. There are no large studies of in-hospital arrhythmia development and outcomes in pediatric patients with acute myocarditis. This was a retrospective 2-center review of patients ≤21 years hospitalized with acute myocarditis from 1996 to 2012. Fulminant myocarditis was defined as the need for inotropic support within 24 hours of presentation. Acute arrhythmias occurred at presentation and subacute after admission. Eighty-five patients (59% men) presented at a median age of 10 years (1 day to 18 years). Arrhythmias occurred in 38 patients (45%): 16 acute, 12 subacute, and 9 acute and subacute (1 onset unknown). Arrhythmias were associated with low voltages on the electrocardiogram (14 of 34, 41% vs 6 of 47, 13%; odds ratio [OR] 4.78, 95% confidence interval [CI] 1.60 to 14.31) and worse outcome (mechanical support, orthotopic heart transplant, or death; OR 7.59, 95% CI 2.61 to 22.07) but were not statistically significantly associated with a fulminant course, ST changes, initial myocardial function, lactate, creatinine level, C-reactive protein and/or erythrocyte sedimentation rate, or troponin I level, after adjusting for multiple comparisons. Subacute arrhythmias were associated with preceding ST changes (10 of 15, 67% vs 15 of 59, 25%, OR 5.87, 95% CI 1.73 to 19.93). All patients surviving to discharge had arrhythmia resolution or control before discharge (10 on antiarrhythmic), with 1 exception (patient with complete heart block requiring a pacemaker). At 1-year follow-up, there were 3 recurrences of ventricular arrhythmias, but no arrhythmia-related mortality. In conclusion, arrhythmias are common in pediatric patients with myocarditis, occurring in nearly 1/2 of all hospitalized children and are associated with a worse outcome. Early identification of subacute arrhythmias using electrocardiographic changes may help management. A majority of patients do not require continued postdischarge arrhythmia treatment.

View details for DOI 10.1016/j.amjcard.2013.10.021

View details for Web of Science ID 000331161700022
Electrophysiologic Therapeutics in Heart Failure in Adult Congenital Heart Disease HEART FAILURE CLINICS Motonaga, K. S., Khairy, P., Dubin, A. M. 2014; 10 (1): 69-?
View details for DOI 10.1016/j.hfc.2013.09.011

View details for Web of Science ID 000329086600009
Diagnostic Tools for Arrhythmia Detection in Adults with Congenital Heart Disease and Heart Failure HEART FAILURE CLINICS Mondesert, B., Dubin, A. M., Khairy, P. 2014; 10 (1): 57-?
Abstract

As patients with congenital heart disease age with increasingly complex lesions, heart failure and arrhythmias have emerged as leading sources of morbidity and mortality. The two are intertwined, as one may herald, beget, or aggravate the other. Moreover, arrhythmias in adults with congenital heart disease and heart failure can be poorly tolerated or life threatening. There is, therefore, much interest in promptly and accurately diagnosing arrhythmias and identifying risk factors for sudden death. This article appraises current knowledge regarding diagnostic tools for arrhythmias in adults with congenital heart disease and heart failure and comments on their prognostic value where relevant.

View details for DOI 10.1016/j.hfc.2013.09.009

View details for Web of Science ID 000329086600008

View details for PubMedID 24275295
Electrophysiologic therapeutics in heart failure in adult congenital heart disease. Heart failure clinics Motonaga, K. S., Khairy, P., Dubin, A. M. 2014; 10 (1): 69-89
Abstract

Arrhythmias have long been recognized as a major cause of morbidity and mortality in the adult with congenital heart disease. It is important that the clinician accurately diagnoses these disturbances and is cognizant of the full array of antiarrhythmic agents and devices available to treat these conditions. This review discusses the most common arrhythmias encountered in this population and the therapeutic options available. Specific issues unique to this population are also addressed.

View details for DOI 10.1016/j.hfc.2013.09.011

View details for PubMedID 24275296
Hot Topics in Tetralogy of Fallot JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Villafane, J., Feinstein, J. A., Jenkins, K. J., Vincent, R. N., Walsh, E. P., Dubin, A. M., Geva, T., Towbin, J. A., Cohen, M. S., Fraser, C., Dearani, J., Rosenthal, D., Kaufman, B., Graham, T. P. 2013; 62 (23): 2155-2166
Abstract

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. We explore "hot topics" to highlight areas of emerging science for clinicians and scientists in moving toward a better understanding of the long-term management of patients with repaired TOF. From a genetic perspective, the etiology of TOF is multifactorial, with a familial recurrence risk of 3%. Cardiac magnetic resonance is the gold standard assessment tool based on its superior imaging of the right ventricular (RV) outflow tract, pulmonary arteries, aorta, and aortopulmonary collaterals, and on its ability to quantify biventricular size and function, pulmonary regurgitation (PR), and myocardial viability. Atrial re-entrant tachycardia will develop in more than 30% of patients, and high-grade ventricular arrhythmias will be seen in about 10% of patients. The overall incidence of sudden cardiac death is estimated at 0.2%/yr. Risk stratification, even with electrophysiologic testing and cardiac magnetic resonance, remains imperfect. Drug therapy has largely been abandoned, and defibrillator placement, despite its high risks for complications and inappropriate discharges, is often recommended for patients at higher risk. Definitive information about optimal surgical strategies for primary repair to preserve RV function, reduce arrhythmia, and optimize functional status is lacking. Post-operative lesions are often amenable to transcatheter intervention. In selected cases, PR may be treated with transcatheter valve insertion. Ongoing surveillance of RV function is a crucial component of clinical assessment. Except for resynchronization with biventricular pacing, no medical therapies have been shown to be effective after RV dysfunction occurs. In patients with significant PR with RV dilation, optimal timing of pulmonary valve replacement remains uncertain, although accepted criteria are emerging.

View details for DOI 10.1016/j.jacc.2013.07.100

View details for Web of Science ID 000328073000002
Do Pediatric Electrophysiologists Read Pre-Participation Screening Electrocardiograms More Accurately than General Pediatric Cardiologists? JOURNAL OF PEDIATRICS Harbison, A. L., Hill, A. C., Motonaga, K. S., Miyake, C. Y., Dubin, A. M. 2013; 163 (6): 1775-1777
Abstract

Pre-participation electrocardiogram (ECG) screening of athletes is controversial. Pediatric electrophysiologists do not interpret screening ECGs more accurately than pediatric cardiologists with average number of correct ECG interpretations of 13.1-12.4 (P = .14). Electrophysiologists ordered fewer follow-up tests and were more likely to give sports recommendations based on published guidelines.

View details for DOI 10.1016/j.jpeds.2013.07.034

View details for Web of Science ID 000327543200050
The effects of ketamine on dexmedetomidine-induced electrophysiologic changes in children PEDIATRIC ANESTHESIA Char, D., Drover, D. R., Motonaga, K. S., Gupta, S., Miyake, C. Y., Dubin, A. M., Hammer, G. B. 2013; 23 (10): 898-905
Abstract

BACKGROUND: Dexmedetomidine is an alpha2-adrenergic agonist used for sedation and analgesia in children. We previously showed that dexmedetomidine depresses sinus and AV nodal function resulting in adverse hemodynamic effects such as bradycardia and increased blood pressure. We hypothesized that these effects of dexmedetomidine might be antagonized by co-administration of ketamine, which has sympathomimetic properties. METHODS: Twenty-two children (ages 5-17 years) undergoing electrophysiologic (EP) study and ablation for supraventricular tachycardia were enrolled. Patients were kept sedated with continuous infusion of propofol at a fixed rate. Hemodynamic and EP parameters were measured before and after a loading dose of dexmedetomidine (1 μg·kg(-1) ). A continuous infusion of dexmedetomidine (0.7 μg·kg(-1) ·h(-1) ) was initiated and a ketamine loading dose (1 mg·kg(-1) ), followed by continuous infusion (1 mg·kg(-1) ·h(-1) ), was given. A repeat set of hemodynamic and EP parameters were then measured at the time of projected peak tissue concentration for both drugs. RESULTS: A significant increase in mean arterial pressure (MAP) was seen compared with baseline after loading of dexmedetomidine. This returned to baseline after co-administration of ketamine (mean difference between baseline and after ketamine 1.8 mmHg; 95%CI, -7.8 to 4.3; P = <0.001). A decrease in heart rate was seen after dexmedetomidine followed by a return to baseline after co-administration of ketamine (mean difference between baseline and after ketamine -6.5 bpm; 95%CI, -11.2 to -1.8; P = 0.005). Sinus node recovery time was lengthened after dexmedetomidine but returned to baseline after ketamine (mean difference between baseline and after ketamine -16.2 ms; 95%CI, -63 to 30; P = 0.014). QT was prolonged after dexmedetomidine and returned to baseline after ketamine (mean difference between baseline and after ketamine -34.2 ms; 95%CI, -48.4 to -20.2; P = 0.004). AV nodal effective refractory period was also impaired after dexmedetomidine and showed weak evidence for return to baseline function after ketamine (mean difference between baseline and after ketamine -22.8 ms; 95%CI, -40.2 to -5.2; P = 0.069). CONCLUSION: The concurrent use of ketamine may mitigate the negative chronotropic effects of dexmedetomidine.

View details for DOI 10.1111/pan.12143

View details for Web of Science ID 000323885500004
QRS prolongation is strongly associated with life-threatening ventricular arrhythmias in children with dilated cardiomyopathy JOURNAL OF HEART AND LUNG TRANSPLANTATION Dao, D. T., Hollander, S. A., Rosenthal, D. N., Dubin, A. M. 2013; 32 (10): 1013-1019
Abstract

The incidence of sudden death in children with dilated cardiomyopathy has been estimated at < 1% annually. This number, however, may underestimate the incidence of life-threatening arrhythmias. The objective of this study was to assess the incidence of and identify risk factors for life-threatening arrhythmias in children with dilated cardiomyopathy.We conducted a retrospective record review of 183 children with dilated cardiomyopathy treated at a single center between 2000 and 2011. Life-threatening arrhythmia was defined as any ventricular arrhythmia that resulted in syncope or hypotension and required medical intervention. Risk factors for life-threatening arrhythmias were identified with univariate analyses. A prediction model was constructed with multivariate logistic regression and receiver operating characteristic curves.Nineteen patients experienced life-threatening arrhythmias, representing an annualized rate of 4.9%. Outpatient life-threatening arrhythmias occurred at a rate of 2.2% per year. Predictors of outpatient life-threatening arrhythmias were longer QRS duration (p = 0.003) and increased left ventricular posterior wall (LVPWd) thickness (p = 0.03). Only QRS duration remained significant in multivariate logistic regression (odds ratio, 1.8 for every unit increase in z-score; 95% CI, 1.01-1.9; p = 0.04). For all life-threatening arrhythmias, prolonged QRS duration was the only significant risk factor in multivariate logistic regression (odds ratio, 1.5; 95% CI, 1.1-2.2; p = 0.02).In children with dilated cardiomyopathy, as QRS duration increases, so too does the risk of life-threatening arrhythmias. Life-threatening arrhythmias occurred at an annual rate of 5%, which was much higher than the previously reported rate of sudden cardiac death in this population.

View details for DOI 10.1016/j.healun.2013.06.007

View details for Web of Science ID 000325044600010
The Multicenter Pediatric and Adult Congenital EP Quality (MAP-IT) Initiative-Rationale and Design: Report from the Pediatric and Congenital Electrophysiology Society's MAP-IT Taskforce CONGENITAL HEART DISEASE Seslar, S. P., Kugler, J., Batra, A. S., Collins, K. K., Crosson, J., Dubin, A. M., Etheridge, S., Kanter, R., Papez, A., Radbill, A. E., Serwer, G. A., Tanel, R. E., Tsao, S., Webster, G., Saarel, E. V. 2013; 8 (5): 381-392
Abstract

Multicenter clinical registries are increasingly recognized as valuable tools for establishing benchmarks, facilitating patient-centered quality improvement and research. In 2010, the Pediatric and Congenital Electrophysiology Society convened a taskforce of its members to design, construct, and implement a clinical registry known as the Multicenter Pediatric and Adult Congenital EP Quality (MAP-IT) Initiative. The present aim of the MAP-IT Initiative is to create an infrastructure by which we can measurably improve patient-centered outcomes and reduce complications associated with electrophysiology studies and catheter ablation in pediatric and congenital heart disease patients. The purpose of this writing is to report the progress to date from three of the four subcommittees of the MAP-IT taskforce. Specifically, we present our initial set of key data elements and definitions, recommended database table structure, and considerations regarding wide-scale implementation of the registry. Development of a risk/complexity score for use in the MAP-IT registry is presented in a separate companion manuscript. It is our intent that these manuscripts will serve to introduce the electrophysiology and pediatric cardiology community to the MAP-IT initiative and provide a rationale for its design and recommended implementation strategy.

View details for DOI 10.1111/chd.12084

View details for Web of Science ID 000324924600011

View details for PubMedID 23663492
Infant ventricular fibrillation after ST-segment changes and QRS widening: a new cause of sudden infant death? Circulation. Arrhythmia and electrophysiology Miyake, C. Y., Davis, A. M., Motonaga, K. S., Dubin, A. M., Berul, C. I., Cecchin, F. 2013; 6 (4): 712-718
Abstract

BACKGROUND: -Ventricular arrhythmia related sudden cardiac arrest in infants with structurally normal hearts is rare. There have been no previously published reports of infants less than 3 months of age with ventricular fibrillation in which a primary diagnosis could not be defined. METHODS AND RESULTS: -Retrospective chart review of 3 unrelated infants less than 2 months of age from 3 different tertiary care centers within the United States and Australia. All 3 infants survived sudden cardiac arrest secondary to multiple episodes of polymorphic ventricular tachycardia and ventricular fibrillation. Each infant demonstrated unique and transient ECG findings consisting of ST changes and QRS widening prior to arrhythmia onset that have not been previously reported. Amiodarone, sedation, sodium channel blocking agents and/or ventricular pacing were effective in suppressing acute events. Despite thorough investigation including genetic testing, the etiology of the ventricular arrhythmias in each of these infants remains unclear. CONCLUSIONS: -This is the first report of idiopathic ventricular fibrillation in young infants preceded by stereotypical transient ECG changes. These findings may represent a new, potentially treatable cause of sudden infant death. Recognition of these prodromal changes may be important in future management and survival of these infants.

View details for DOI 10.1161/CIRCEP.113.000444

View details for PubMedID 23748209
Infant Ventricular Fibrillation After ST-Segment Changes and QRS Widening A New Cause of Sudden Infant Death? CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Miyake, C. Y., Davis, A. M., Motonaga, K. S., Dubin, A. M., Berul, C. I., Cecchin, F. 2013; 6 (4): 712-718
View details for DOI 10.1161/CIRCEP.113.000444

View details for Web of Science ID 000323323900019
Multi-Institutional Study of Implantable Defibrillator Lead Performance in Children and Young Adults: Results of the Pediatric Lead Extractability and Survival Evaluation (PLEASE) Study CIRCULATION Atallah, J., Erickson, C. C., Cecchin, F., Dubin, A. M., Law, I. H., Cohen, M. I., LaPage, M. J., Cannon, B. C., Chun, T. U., Freedenberg, V., Gierdalski, M., Berul, C. I. 2013; 127 (24): 2393-2402
Abstract

Implantable cardioverter-defibrillator (ICD) therapy in children and congenital heart disease patients is hampered by poor long-term lead survival. Lead extraction is technically difficult and carries substantial morbidity. We sought to determine the outcomes of ICD leads in pediatric and congenital heart disease patients.The Pediatric Lead Extractability and Survival Evaluation (PLEASE) is a 24-center international registry. Pediatric and congenital heart disease patients with ICD lead implantations from 2005 to 2010 were eligible. Study subjects comprised 878 ICD patients (44% congenital heart disease). Mean±SD age at implantation was 18.6±9.8 years. Of the 965 total leads, 54% were thin (≤7F), of which 57% were Fidelis, and 23% were coated with expanded polytetrafluoroethylene. There were 139 ICD lead failures (14%) in 132 patients (15%) at a mean lead age of 2.0±1.4 years, causing shocks in 53 patients (40%). Independent predictors of lead failure included younger implantation age and Fidelis leads. Actuarial analysis showed an incremental risk of lead failure with younger age at implantation: <8 years compared with >18 years (P=0.015). The actuarial yearly failure rate was 2.3% for non-Fidelis and 9.1% for Fidelis leads. Extraction was performed on 143 leads (80% thin, 7% expanded polytetrafluoroethylene coated), with lead age as the only independent predictor for advanced extraction techniques. There were 6 major extraction complications (4%) but no procedural mortality.This study demonstrates that ICD leads in children and congenital heart disease patients have an age-related suboptimal performance, further compounded by a high failure rate of Fidelis leads. Advanced extraction techniques were common and correlated with older lead age.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00335036.

View details for DOI 10.1161/CIRCULATIONAHA.112.001120

View details for Web of Science ID 000320699100018

View details for PubMedID 23694966
Fascicular and Nonfascicular Left Ventricular Tachycardias in the Young: An International Multicenter Study JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Collins, K. K., Schaffer, M. S., Liberman, L., Saarel, E., Knecht, M., Tanel, R. E., Bradley, D., Dubin, A. M., Paul, T., Salerno, J., Bar-Cohen, Y., Sreeram, N., Sanatani, S., Law, I. H., Blaufox, A., Batra, A., Moltedo, J. M., Van Hare, G. F., Reed, J., Ro, P. S., Kugler, J., Anderson, C., Triedman, J. K. 2013; 24 (6): 640-648
Abstract

The aim of this study was to evaluate the clinical presentation and outcomes of pediatric patients with ventricular tachycardia (VT) originating from left heart structures.This international multicenter retrospective study including 152 patients (age 10.0 ± 5.1 years, 62% male), divided into those with fascicular VT (85%, 129/152) and nonfascicular LV VT (15%, 23/152). All patients had a normal heart structure or only a minor cardiac abnormality. Adenosine was largely ineffective in both groups (tachycardia termination in 4/74 of fascicular VT and 0/5 of nonfascicular LV VT). In fascicular VT, calcium channel blockers were effective in 80% (74/92); however, when administered orally, there was a 21% (13/62) recurrence rate. In nonfascicular LV VT, a variety of antiarrhythmic therapies were used with no one predominating. Ablation procedures were successful in 71% (72/102) of fascicular VT and 67% (12/18) of nonfascicular LV VT on an intention to treat analysis. Major complications occurred in 5 patients with fascicular VT and 1 patient with nonfascicular LV VT. After a follow-up period of 2 years (1 day to 15 years), 72% of all patients with fascicular VT were off medications with no tachycardia recurrence. One patient died of noncardiac causes. In nonfascicular LV VT, follow-up was 3.5 years (0.5-15 years), P = 0.38. A total of 65% of these patients were free from arrhythmias. Two patients died suddenly (P < 0.01).The clinical course and outcomes of pediatric patients with fascicular VT and nonfascicular LV VT are varied. Catheter ablation procedures can be curative.

View details for DOI 10.1111/jce.12105

View details for Web of Science ID 000319898500006
Efficacy of Implantable Cardioverter Defibrillators in Young Patients With Catecholaminergic Polymorphic Ventricular Tachycardia: Success Depends on Substrate CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Miyake, C. Y., Webster, G., Czosek, R. J., Kantoch, M. J., Dubin, A. M., Avasarala, K., Atallah, J. 2013; 6 (3): 579-587
View details for DOI 10.1161/CIRCEP.113.000170

View details for Web of Science ID 000320760200026
Efficacy of implantable cardioverter defibrillators in young patients with catecholaminergic polymorphic ventricular tachycardia: success depends on substrate. Circulation. Arrhythmia and electrophysiology Miyake, C. Y., Webster, G., Czosek, R. J., Kantoch, M. J., Dubin, A. M., Avasarala, K., Atallah, J. 2013; 6 (3): 579-587
Abstract

BACKGROUND: -The effectiveness of implantable cardioverter-defibrillator (ICD) therapy for the management of catecholaminergic polymorphic ventricular tachycardia (CPVT) in young patients is not known. ICD discharges are not always effective and inappropriate discharges are common, both resulting in morbidity and mortality. METHODS AND RESULTS: -This is a multicenter, retrospective review of young patients with CPVT and ICDs from 5 centers. ICD discharges were evaluated to determine arrhythmia mechanism, appropriateness, efficacy of therapy, and complications. A total of 24 patients were included. Median (IQR) ages at onset of CPVT symptoms and ICD implant were 10.6 (5.0 - 13.8) years and 13.7 (10.7 - 16.3) years respectively. Fourteen patients received 140 shocks. Ten patients (42%) experienced 75 appropriate shocks and 11 patients (46%) received 65 inappropriate shocks. On actuarial analysis, freedom from appropriate shock at 1 year after ICD implant was 75%. Of appropriate shocks, only 43 (57%) demonstrated successful primary termination. All successful appropriate ICD discharges were for ventricular fibrillation (VF). No episodes of polymorphic ventricular tachycardia or bidirectional VT demonstrated successful primary termination. The adjusted mean (95% CI) cycle length of successful discharges was significantly shorter than unsuccessful discharges (168 (152-184) msec vs. 245 (229-262) msec, adjusted p=0.002). Electrical storm occurred in 29% (4/14) and induction of more malignant ventricular arrhythmias in 36% (5/14). There were no deaths. CONCLUSIONS: -ICD efficacy in CPVT depends on arrhythmia mechanism. Episodes of VF were uniformly successfully treated whereas polymorphic and bidirectional VT did not demonstrate successful primary termination. Inappropriate shocks, electrical storm and ICD complications were common.

View details for DOI 10.1161/CIRCEP.113.000170

View details for PubMedID 23667268
Insights into dyssynchrony in Hypoplastic Left Heart Syndrome HEART RHYTHM Motonaga, K. S., Miyake, C. Y., Punn, R., Rosenthal, D. N., Dubin, A. M. 2012; 9 (12): 2010-2015
Abstract

Cardiac resynchronization therapy has been proposed for treatment of hypoplastic left heart syndrome (HLHS) patients with right ventricular (RV) failure. The role of dyssynchrony, however, is poorly understood in this population.The purpose of this study was to better understand the relationship between electrical and mechanical dyssynchrony in HLHS using 3-dimensional electrical mapping, tissue Doppler indices of wall motion, and vector velocity imaging.Eleven HLHS subjects with normal RV function and ten normal subjects (age 3-18 years) were studied. Electrical and mechanical activation times and dyssynchrony indices (electrical dyssynchrony index, mechanical dyssynchrony index) were calculated using 3-dimensional electrical mapping, tissue Doppler indices, and vector velocity imaging.No differences in measures of electrical dyssynchrony were seen when comparing HLHS patients and normal patients (electrical activation time 63.3 ± 22.8 ms vs 56.2 ± 11.2 ms, P = .38; electrical dyssynchrony index 13.7 ± 6.3 ms vs 11.6 ± 3.0 ms, P = .34). However, measures of mechanical dyssynchrony were markedly abnormal in HLHS patients despite normal RV function (mechanical activation time 16 ± 11.3 ms vs 0.9±1.9 ms, P = .01; mechanical dyssynchrony index 7.5 ± 5.5 vs 0.4 ± 0.8, P<.01).Patients with HLHS and preserved RV systolic function have normal electrical activation when compared to patients with normal right and left ventricles. In contrast, these patients demonstrate mechanical dyssynchrony compared to patients with normal right and left ventricles. This finding raises important questions about the indications for cardiac resynchronization therapy in this patient population.

View details for DOI 10.1016/j.hrthm.2012.08.031

View details for Web of Science ID 000311791900029

View details for PubMedID 23085485
Pediatric cardiovascular safety: Challenges in drug and device development and clinical application AMERICAN HEART JOURNAL Bates, K. E., Vetter, V. L., Li, J. S., Cummins, S., Aguel, F., Almond, C., Dubin, A. M., Elia, J., Finkle, J., Hausner, E. A., Joseph, F., Karkowsky, A. M., Killeen, M., Lemacks, J., Mathis, L., McMahon, A. W., Pinnow, E., Rodriguez, I., Stockbridge, N. L., Stockwell, M., Tassinari, M., Krucoff, M. W. 2012; 164 (4): 481-492
Abstract

Development of pediatric medications and devices is complicated by differences in pediatric physiology and pathophysiology (both compared with adults and within the pediatric age range), small patient populations, and practical and ethical challenges to designing clinical trials. This article summarizes the discussions that occurred at a Cardiac Safety Research Consortium-sponsored Think Tank convened on December 10, 2010, where members from academia, industry, and regulatory agencies discussed important issues regarding pediatric cardiovascular safety of medications and cardiovascular devices. Pediatric drug and device development may use adult data but often requires additional preclinical and clinical testing to characterize effects on cardiac function and development. Challenges in preclinical trials include identifying appropriate animal models, clinically relevant efficacy end points, and methods to monitor cardiovascular safety. Pediatric clinical trials have different ethical concerns from adult trials, including consideration of the subjects' families. Clinical trial design in pediatrics should assess risks and benefits as well as incorporate input from families. Postmarketing surveillance, mandated by federal law, plays an important role in both drug and device safety assessment and becomes crucial in the pediatric population because of the limitations of premarketing pediatric studies. Solutions for this wide array of issues will require collaboration between academia, industry, and government as well as creativity in pediatric study design. Formation of various epidemiologic tools including registries to describe outcomes of pediatric cardiac disease and its treatment as well as cardiac effects of noncardiovascular medications, should inform preclinical and clinical development and improve benefit-risk assessments for the patients. The discussions in this article summarize areas of emerging consensus and other areas in which consensus remains elusive and provide suggestions for additional research to further our knowledge and understanding of this topic.

View details for DOI 10.1016/j.ahj.2012.07.019

View details for Web of Science ID 000310506000010

View details for PubMedID 23067905
Electrical and mechanical dyssynchrony in pediatric pulmonary hypertension JOURNAL OF HEART AND LUNG TRANSPLANTATION Hill, A. C., Maxey, D. M., Rosenthal, D. N., Siehr, S. L., Hollander, S. A., Feinstein, J. A., Dubin, A. M. 2012; 31 (8): 825-830
Abstract

Electrical and mechanical dyssynchrony are often seen in patients with left ventricular failure. In pediatric pulmonary hypertension (PH), right ventricular failure predominates; however, the prevalence of electrical and/or mechanical dyssynchrony in these patients is unknown. We examined the prevalence of electrical and mechanical dyssynchrony in pediatric PH patients.Medical records (including, functional status, electrocardiograms and echocardiograms) of pediatric PH patients were reviewed. QRS duration z-scores were calculated to determine electrical dyssynchrony. Echo vector velocity imaging was used to calculate the mechanical dyssynchrony index (DI).Seventy-seven PH patients (idiopathic pulmonary arterial hypertension [IPAH]: n = 26; congenital heart disease: n = 41; other: n = 10) were studied. Electrical dyssynchrony was seen in 84% (p < 0.01 vs historic controls), with a mean z-score of 4.3 (95% CI 3.5 to 5.1). There was no difference between those with IPAH, z = 3.6 (95% CI 2.5 to 4.6), and those without, z = 4.7 (95% CI 3.6 to 5.8). Mechanical dyssynchrony was seen in 76% of patients (mean DI = 66 ± 47 vs 18 ± 8 milliseconds in historic controls, p < 0.01) in both IPAH and non-IPAH patients. Post-operative congenital heart disease patients had the largest dyssynchrony index. No correlation was found among electrical or mechanical dyssynchrony, hemodynamics or disease severity.Significant electrical and mechanical dyssynchrony is present in pediatric PH patients, regardless of etiology. The overall effect of electrical and mechanical dyssynchrony on outcomes in this patient population is still unknown. Select patients may benefit from resynchronization therapy.

View details for DOI 10.1016/j.healun.2012.04.004

View details for Web of Science ID 000306449000006

View details for PubMedID 22682994
Clinical and Electrophysiologic Characteristics of Antidromic Tachycardia in Children with Wolff-Parkinson-White Syndrome PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Ceresnak, S. R., Tanel, R. E., Pass, R. H., Liberman, L., Collins, K. K., Van Hare, G. F., Gates, G. J., Dubin, A. M. 2012; 35 (4): 480-488
Abstract

Antidromic reciprocating tachycardia (ART) is a rare form of wide complex tachycardia in children with Wolff-Parkinson-White syndrome (WPW). The incidence and electrophysiologic characteristics of ART in children with WPW have not been well described.A multicenter retrospective analysis of all patients with WPW undergoing electrophysiology (EP) study from 1990 to 2009 was performed. Patients with clinical or inducible ART were included.A total of 1,147 patients with WPW underwent EP study and 30 patients had ART (2.6%) and were the subject of this analysis. The mean age was 16±3 years, weight was 65±16 kg, and tachycardia cycle length was 305±55 ms. There were two patients (7%) with congenital heart disease (both with Ebstein's anomaly). Four patients (13%) had more than one accessory pathway (AP). The location of the AP was left sided in 53% of patients and right sided in 47%, with septal location and left lateral pathways most commonly involved. AP conduction was found to be high risk in 17 patients (57%). Ablation was not attempted in two patients (7%) due to proximity to the HIS and risk of heart block. Ablation was acutely successful in 93% of the patients in whom it was attempted.ART is a rare finding in children undergoing EP study. Over half of the patients with ART were found to be high risk and multiple AP were uncommon. Unlike the adult population, ART occurred commonly with septal APs.

View details for DOI 10.1111/j.1540-8159.2011.03317.x

View details for Web of Science ID 000302540300024

View details for PubMedID 22324823
Is There a Rote for Cardiac Resynchronization Therapy in Pediatric Pulmonary Hypertension? Motonaga, K. S., MIYAKE, C. Y., Punn, R., Rosenthal, D. N., Feinstein, J. A., Dubin, A. M. ELSEVIER SCIENCE INC. 2012: S29-S29
View details for Web of Science ID 000302207900059
Hypoplastic Left Heart Syndrome Current Considerations and Expectations JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Feinstein, J. A., Benson, D. W., Dubin, A. M., Cohen, M. S., Maxey, D. M., Mahle, W. T., Pahl, E., Villafane, J., Bhatt, A. B., Peng, L. F., Johnson, B. A., Marsden, A. L., Daniels, C. J., Rudd, N. A., Caldarone, C. A., Mussatto, K. A., Morales, D. L., Ivy, D. D., Gaynor, J. W., Tweddell, J. S., Deal, B. J., Furck, A. K., Rosenthal, G. L., Ohye, R. G., Ghanayem, N. S., Cheatham, J. P., Tworetzky, W., Martin, G. R. 2012; 59 (1): S1-S42
Abstract

In the recent era, no congenital heart defect has undergone a more dramatic change in diagnostic approach, management, and outcomes than hypoplastic left heart syndrome (HLHS). During this time, survival to the age of 5 years (including Fontan) has ranged from 50% to 69%, but current expectations are that 70% of newborns born today with HLHS may reach adulthood. Although the 3-stage treatment approach to HLHS is now well founded, there is significant variation among centers. In this white paper, we present the current state of the art in our understanding and treatment of HLHS during the stages of care: 1) pre-Stage I: fetal and neonatal assessment and management; 2) Stage I: perioperative care, interstage monitoring, and management strategies; 3) Stage II: surgeries; 4) Stage III: Fontan surgery; and 5) long-term follow-up. Issues surrounding the genetics of HLHS, developmental outcomes, and quality of life are addressed in addition to the many other considerations for caring for this group of complex patients.

View details for DOI 10.1016/j.jacc.2011.09.022

View details for Web of Science ID 000298370300001

View details for PubMedID 22192720
Accuracy of Interpretation of Preparticipation Screening Electrocardiograms JOURNAL OF PEDIATRICS Hill, A. C., Miyake, C. Y., Grady, S., Dubin, A. M. 2011; 159 (5): 783-788
Abstract

To evaluate the accuracy of pediatric cardiologists' interpretations of electrocardiograms (ECGs).A series of 18 ECGs that represented conditions causing pediatric sudden cardiac death or normal hearts were interpreted by 53 members of the Western Society of Pediatric Cardiology. Gold-standard diagnoses and recommendations were determined by 2 electrophysiologists (100% concordance).The average number of correct ECG interpretations per respondent was 12.4 ± 2.2 (69%, range 34%-98%). Respondents achieved a sensitivity of 68% and a specificity of 70% for recognition of any abnormality. The false-positive and false-negative rates were 30% and 32%, respectively. Based on actual ECG diagnosis, sports participation was accurately permitted in 74% of cases and accurately restricted in 81% of cases. Respondents gave correct sports guidance most commonly in cases of long QT syndrome and myocarditis (98% and 90%, respectively) and least commonly in cases of hypertrophic cardiomyopathy, Wolff-Parkinson-White syndrome, and pulmonary hypertension (80%, 64%, and 38%, respectively). Respondents ordered more follow-up tests than did experts.Preparticipation screening ECGs are difficult to interpret. Mistakes in ECG interpretation could lead to high rates of inappropriate sports guidance. A consequence of diagnostic error is overuse of ancillary diagnostic tests.

View details for DOI 10.1016/j.jpeds.2011.05.014

View details for Web of Science ID 000296581100019

View details for PubMedID 21752393
Pediatric pacemakers and ICDs: how to optimize perioperative care PEDIATRIC ANESTHESIA Navaratnam, M., Dubin, A. 2011; 21 (5): 512-521
Abstract

An increasing number of pediatric patients with permanent pacemakers and implantable cardioverter defibrillators (ICDs) require cardiac and noncardiac surgery. It is critical that the anesthesiologist caring for these patients understands the management of the device and the underlying heart disease. Children with these devices are more vulnerable to lead failure and inappropriate shocks compared with the adult population. Preoperative assessment and appropriate reprogramming of the device, in addition to minimizing sources of electromagnetic interference, are keystones in the perioperative care of these patients. Prior consultation with qualified programmers is recommended to enable timely optimization of the device. Magnets may be used in emergency situations but it is important to appreciate the limitations of magnet use on different models of pacemakers and ICDs. Safe and successful perioperative care is dependent upon a well-organized and coordinated multidisciplinary team approach.

View details for DOI 10.1111/j.1460-9592.2011.03562.x

View details for Web of Science ID 000289469500006

View details for PubMedID 21481077
Survival after extreme left atrial hypertension and pulmonary hemorrhage in an infant supported with extracorporeal membrane oxygenation for refractory atrial flutter PEDIATRIC CRITICAL CARE MEDICINE Cisco, M. J., Asija, R., Dubin, A. M., Perry, S. B., Hanley, F. L., Roth, S. J. 2011; 12 (3): E149-E152
Abstract

We report here the survival of an infant who developed extreme left atrial hypertension and severe pulmonary hemorrhage while supported with extracorporeal membrane oxygenation for refractory atrial flutter. The patient recovered after decompression of the left heart and catheter ablation of the atrioventricular node.Lucile Packard Children's Hospital (Stanford, CA).Chart review.Recovery of lung function is possible despite systemic-level left atrial pressure resulting in pulmonary hemorrhage and complete solidification of lung parenchyma on gross inspection. Resolution of pulmonary hemorrhage despite anticoagulation while on extracorporeal membrane oxygenation can occur after relief of left atrial hypertension.

View details for DOI 10.1097/PCC.0b013e3181e8b3e5

View details for Web of Science ID 000290248500008

View details for PubMedID 20693934
Electrical Dyssynchrony in Pediatric Pulmonary Arterial Hypertension Hill, A. C., Maxey, D. M., Siehr, S. L., Rosenthal, D. N., Dubin, A. M., Feinstein, J. A. ELSEVIER SCIENCE INC. 2011: S224-S225
View details for Web of Science ID 000288924300670
Quality of Life in Pediatric Patients With Implantable Cardioverter Defibrillators AMERICAN JOURNAL OF CARDIOLOGY Sears, S. F., Hazelton, A. G., St Amant, J., Matchett, M., Kovacs, A., Vazquez, L. D., Fairbrother, D., Redfearn, S., Hanisch, D., Dubin, A., Cannon, B. C., Fishbach, P., Kanter, R., Bryant, R. M. 2011; 107 (7): 1023-1027
Abstract

Psychosocial and quality-of-life (QOL) outcomes in adult patients with implantable cardioverter-defibrillators (ICDs) are well studied. Minimal research exists regarding pediatric adjustment, despite a potentially more challenging adjustment process. The purpose of the present study was to examine psychosocial and QOL functioning of pediatric ICD patients from patient and parent self-reports. Children and primary caregiver dyads from several university hospitals were analyzed using the PedsQL, the Device Severity Index, the ICD and Avoidance Survey, and demographic information. Sixty children (25 female, 35 male) were enrolled. The present pediatric sample reported lower psychosocial and physical QOL scores than healthy children's normative scores. In comparison with a sample of chronically ill children, pediatric ICD patients reported lower physical QOL. Parent-observed QOL reports revealed lower psychosocial and physical QOL than parent-observed healthy norms and lower psychosocial and physical QOL than chronically ill norms. There were no QOL differences by ICD shocks or medical severity. Female patients reported lower psychosocial, physical, and cardiac QOL scores. Children reported better QOL than parent observations on psychosocial and physical health. Finally, 84.7% of children reported avoidance behaviors since ICD implantation, with female children avoiding places more than male children. In conclusion, pediatric ICD patients are comparable to children with other chronic illnesses with the exception of lower physical QOL. Similar to adult samples, female children reported poorer QOL and were more likely to engage in avoidance behaviors. Patients indicated better QOL perceptions than their parents' reports. ICD discharges and medical severity did not negatively affect QOL.

View details for DOI 10.1016/j.amjcard.2010.11.027

View details for Web of Science ID 000289275500011

View details for PubMedID 21256464
Can Preparticipation Screening Electrocardiograms be Interpreted Accurately? Hill, A. C., Miyake, C. Y., Grady, S. R., Dubin, A. M. LIPPINCOTT WILLIAMS & WILKINS. 2010
View details for Web of Science ID 000208231600624
Are wide complex tachycardia algorithms applicable in children and patients with congenital heart disease? JOURNAL OF ELECTROCARDIOLOGY Ceresnak, S. R., Liberman, L., Avasarala, K., Tanel, R., Motonaga, K. S., Dubin, A. M. 2010; 43 (6): 694-700
Abstract

Several algorithms have been developed to help determine the etiology of wide complex tachycardias (WCTs) in adults. Sensitivity and specificity for differentiating supraventricular tachycardia (SVT) with aberration from ventricular tachycardia (VT) in adults have been demonstrated to be as high as 98% and 97%. These algorithms have not been tested in the pediatric population. We hypothesize that these algorithms have lower diagnostic accuracy in children and patients with congenital heart disease.A retrospective review of the pediatric electrophysiology database at Stanford from 2001 to 2008 was performed. All children with WCT, a 12-lead electrocardiogram (ECG) available for review, and an electrophysiology study confirming the etiology of the rhythm were included. Patients with a paced rhythm were excluded. The ECGs were analyzed by 2 electrophysiologists blinded to the diagnosis according to the algorithms described in Brugada et al,(2) and Vereckei et al.(5) Additional ECG findings were recorded by each electrophysiologist.A total of 65 WCT ECGs in 58 patients were identified. Supraventricular tachycardia was noted in 62% (40/65) and VT in 38% (25/65) of the ECGs. The mean age was 13.5 years (SD ± 5.1), the mean weight was 51.8 kg (SD ± 22.4), and 48% (31/65) were male. The mean tachycardia cycle length was 340 milliseconds (SD ± 95). Congenital heart disease (CHD) was present in 37% (24/65) of patients (7 tetralogy of Fallot, 6 Ebstein's, 4 double-outlet right ventricle, 3 complex CHD, 2 d-transposition of great arteries, 1 status-post orthotopic heart transplantation, 1 ventricular septal defect). The Brugada algorithm correctly predicted the diagnosis 69% (45/65) of the time, the Vereckei algorithm correctly predicted the diagnosis 66% (43/65) of the time, and the blinded reviewer correctly predicted the diagnosis 78% (51/65) of the time. There was no difference in the efficacy of the algorithms in patients with CHD vs those with structurally normal hearts. The findings of left superior axis deviation (P < .01) and a notch in the QRS downstroke of V(1) or V(2) (P < .01) were more common in VT than SVT, whereas a positive QRS deflection in V(1) (P = .03) was more commonly present in SVT than VT.The Brugada and Vereckei algorithms have lower diagnostic accuracy in the pediatric population and in patients with congenital heart disease than in the adult population. Left superior axis deviation and a notch in the QRS downstroke were more commonly associated with VT, whereas a positive QRS deflection in V(1) was more commonly associated with SVT in this population.

View details for DOI 10.1016/j.jelectrocard.2010.02.008

View details for Web of Science ID 000284514700039

View details for PubMedID 20382398
Arrhythmogenic forms of heart failure in children. Heart failure clinics Berger, S., Dubin, A. M. 2010; 6 (4): 471-?
Abstract

There are various underlying causes of tachycardia-induced cardiomyopathy (TIC), and it is critical that it be considered in any patient who presents with a newly diagnosed dilated cardiomyopathy. Unlike most other forms of cardiomyopathy, TIC should be considered a treatable form of cardiomyopathy and it is imperative that the diagnosis be fully considered. A 12-lead ECG should be obtained in all patients with a dilated cardiomyopathy. Prompt diagnosis and therapy of this relatively uncommon cause of heart failure is critical and has the potential to completely reverse the ventricular dysfunction that may be present in this abnormality.

View details for DOI 10.1016/j.hfc.2010.05.006

View details for PubMedID 20869647
New Insights into Pacemaker Lead-Induced Venous Occlusion: Simulation-Based Investigation of Alterations in Venous Biomechanics CARDIOVASCULAR ENGINEERING Lonyai, A., Dubin, A. M., Feinstein, J. A., Taylor, C. A., Shadden, S. C. 2010; 10 (2): 84-90
Abstract

Venous obstruction is a major complication of transvenous pacemaker placement. Despite the increasing use of pacemakers and implantable cardiac defibrillators, a lack of understanding remains with regard to risk factors for the development of device-associated venous obstruction. We hypothesize that computational fluid dynamics simulations can reveal prothrombogenic locations and define thrombosis risk based on patient-specific anatomies. Using anatomic data derived from computed tomography, computer models of the superior vena cava, subclavian, innominate, and internal jugular veins were constructed for three adult patients with transvenous pacemakers. These models were used to perform patient-specific simulations examining blood flow velocity, wall shear stress, and blood pressure, both with and without the presence of the pacing leads. To better quantify stasis, mean exposure time fields were computed from the venous blood flow data. In comparing simulations with leads to those without, evident increases in stasis at locations between the leads and along the surface of the vessels closest to the leads were found. These locations correspond to regions at known risk for thrombosis. This work presents a novel application of computational methods to study blood flow changes induced by pacemaker leads and possible complications such as venous occlusion and thrombosis. This methodology may add to our understanding of the development of lead-induced thrombosis and occlusion in the clinical arena, and enable the development of new strategies to avoid such complications.

View details for DOI 10.1007/s10558-010-9096-x

View details for Web of Science ID 000278717400005

View details for PubMedID 20514553
Cryoablation with an 8-mm Tip Catheter for Pediatric Atrioventricular Nodal Reentrant Tachycardia Is Safe and Efficacious with a Low Incidence of Recurrence PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Silver, E. S., Silva, J. N., Ceresnak, S. R., Chiesa, N. A., Rhee, E. K., Dubin, A. M., Avasarala, K., Van Hare, G. F., Collins, K. K. 2010; 33 (6): 681-686
Abstract

Cryoablation with 4- and 6-mm tip ablation catheters has been demonstrated to be safe and effective in the treatment of atrioventricular nodal reentrant tachycardia (AVNRT) in pediatric patients, albeit with a higher rate of clinical recurrence. Limited information is available regarding efficacy, mid-term outcomes, and complications related to the use of the 8-mm Freezor Max Cryoablation catheter (Medtronic, Minneapolis, MN, USA) in pediatric patients.We performed a retrospective review of all pediatric patients with normal cardiac anatomy who underwent an ablation procedure for treatment of AVNRT using the 8-mm tip Cryoablation catheter at three large pediatric academic arrhythmia centers.Cryoablation with an 8-mm tip catheter was performed in 77 patients for treatment of AVNRT (female n = 40 [52%], age 14.8 +/- 2.2 years, weight 62.0 +/- 13.9 kg). Initial procedural success was achieved in 69 patients (69/76, 91%). Transient second- or third-degree atrioventricular (AV) block was noted in five patients (6.5%). There was no permanent AV block. Of the patients successfully ablated with Cryotherapy, there were two recurrences (2/70, 2.8%) over a follow-up of 11.6 +/- 3.3 months.Cryoablation with an 8-mm tip ablation catheter is both safe and effective with a low risk of recurrence for the treatment of AVNRT in pediatric patients.

View details for DOI 10.1111/j.1540-8159.2010.02706.x

View details for Web of Science ID 000278818200006

View details for PubMedID 20230479
Acute Effects of Single-site Pacing from the Left and Right Ventricle on Ventricular Function and Ventricular-Ventricular Interactions in Children with Normal Hearts CONGENITAL HEART DISEASE Friedberg, M. K., Dubin, A. M., Van Hare, G. F., McDaniel, G., Niksch, A., Rosenthal, D. N. 2009; 4 (5): 356-361
Abstract

We studied, as a physiological benchmark, acute effects of right ventricular (RV) apical, RV outflow, and left ventricular (LV) pacing in children with normal cardiac function on LV and RV function and ventricular-ventricular interactions.The design of the study was a prospective, acute intervention.The study was conducted in a tertiary care electrophysiology laboratory. Population and Methods. Seven children (mean +/- SD, 12 +/- 4 years) were paced after accessory pathway ablation, at baseline (AOO), and with atrioventricular pacing (DOO) from the RV apex, RV outflow, and left ventricle.Right ventricular dP/dT(max) and RV dP/dT(neg) (high-fidelity transducer-tipped catheters, Millar Instruments, Houston, TX, USA), cardiac index (Fick), blood pressure, and QRS duration were measured at each pacing condition. Intra- and interventricular mechanical dyssynchrony, systolic- and diastolic peak tissue velocities, and isovolumic acceleration were recorded by tissue Doppler imaging at the lateral mitral, septal, and tricuspid annuli at each condition. Results at each pacing condition were compared by repeated-measures analysis of variance. Results. Pacing prolonged QRS duration, causing electrical dyssynchrony (86 +/- 19 ms [baseline], 141 +/- 44 ms [RV apex], 121 +/- 18 ms [RV outflow], and 136 +/- 34 ms [LV], P < .01). Right ventricular outflow pacing caused LV intraventricular delay (63 +/- 52 vs. 12 +/- 7 ms, P < .05). Right ventricular apical pacing caused interventricular delay (61 +/- 29 vs. 25 +/- 18 ms, P < .05). There were no significant changes in blood pressure, cardiac index, RV dp/dT(max), RV dP/dT(neg), regional tissue velocities, or isovolumic acceleration during any of the pacing conditions, indicating preserved ventricular function and hemodynamics. No important ventricular-ventricular interactions were seen.In children with normal cardiac anatomy and function, single-site RV apical, RV outflow, and LV pacing induce electromechanical dyssynchrony without significantly changing ventricular function or hemodynamics, or adversely affecting ventricular-ventricular interactions.

View details for DOI 10.1111/j.1747-0803.2009.00327.x

View details for Web of Science ID 000207893900007

View details for PubMedID 19740190
Right ventricular resynchronization: Moving beyond proof of concept HEART RHYTHM Dubin, A. M., Rosenthal, D. N. 2009; 6 (6): 857-859
View details for DOI 10.1016/j.hrthm.2009.03.010

View details for Web of Science ID 000266658800022

View details for PubMedID 19467516
Pacing-Induced Electromechanical Ventricular Dyssynchrony Does Not Acutely Influence Right Ventricular Function and Global Hemodynamics in Children with Normal Hearts JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Friedberg, M. K., Dubin, A. M., Van Hare, G. F., McDaniel, G. M., Niksch, A., Rosenthal, D. N. 2009; 20 (5): 539-544
Abstract

Right ventricular (RV) pacing may be detrimental to ventricular function. However, the acute effects of electromechanical dyssynchrony on RV function are not well characterized in children. We studied acute effects of electromechanical dyssynchrony, induced by RV apical and RV outflow pacing, in children with normal hearts, evaluating electromechanical synchrony, hemodynamic response, and RV function.Seventeen children (mean +/- SD, 12 +/- 4 years) with normal cardiac structure/function were paced after accessory pathway ablation, at baseline (AOO), and with AV pacing (DOO) from the RV apex and RV outflow. QRS duration was determined from surface ECG. Intra- and interventricular mechanical dyssynchrony and regional ventricular function were determined using tissue Doppler imaging. Global RV systolic and diastolic functions were assessed by RV dP/dT(max) and RV dP/dT(neg) using pressure-tipped transducers. Regional RV function was assessed by tissue Doppler imaging. Cardiac index (CI) and blood pressures were measured.RV apical and outflow pacing induced significant electromechanical dyssynchrony manifested by lengthening of the QRS duration, increased LV intraventricular delay (49 +/- 34 ms, 53 +/- 43 ms, respectively, P < 0.001), and increased interventricular delay (60 +/- 29 ms, 55 +/- 37 ms, P < 0.0001) versus AOO pacing. However, there was no change in blood pressure, CI, RV dp/dT(max), RV dP/dT(neg), or regional tissue Doppler velocities, indicating preserved hemodynamics and preserved global and regional RV systolic and diastolic function.In children with normal cardiac function and structure, pacing-induced electromechanical dyssynchrony did not acutely affect RV systolic and diastolic function and did not acutely alter global hemodynamics. Therefore, electromechanical dyssynchrony may only be an important therapeutic target in the setting of decreased RV function.

View details for DOI 10.1111/j.1540-8167.2008.01354.x

View details for Web of Science ID 000265409900012

View details for PubMedID 19017336
Exercise Capacity Is Decreased in Children With Chronic Right Ventricular Pacing and Congenital Complete Heart Block Axelrod, D., Rosenthal, D. N., Chin, C., Obayashi, D., Kazmucha, J., Hanisch, D., Dubin, A. M. ELSEVIER SCIENCE INC. 2009: A359-A359
View details for Web of Science ID 000263864201488
Pediatric Nonpost-Operative Junctional Ectopic Tachycardia Medical Management and Interventional Therapies JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Collins, K. K., Van Hare, G. F., Kertesz, N. J., Law, I. H., Bar-Cohen, Y., Dubin, A. M., Etheridge, S. P., Berul, C. I., Avari, J. N., Tuzcu, V., Sreeram, N., Schaffer, M. S., Fournier, A., Sanatani, S., Snyder, C. S., Smith, R. T., Arabia, L., Hamilton, R., Chun, T., Liberman, L., Kakavand, B., Paul, T., Tanel, R. E. 2009; 53 (8): 690-697
Abstract

To determine the outcomes of medical management, pacing, and catheter ablation for the treatment of nonpost-operative junctional ectopic tachycardia (JET) in a pediatric population.Nonpost-operative JET is a rare tachyarrhythmia that is associated with a high rate of morbidity and mortality. Most reports of clinical outcomes were published before the routine use of amiodarone or ablation therapies.This is an international, multicenter retrospective outcome study of pediatric patients treated for nonpost-operative JET.A total of 94 patients with JET and 5 patients with accelerated junctional rhythm (age 0.8 year, range fetus to 16 years) from 22 institutions were identified. JET patients presenting at age < or =6 months were more likely to have incessant JET and to have faster JET rates. Antiarrhythmic medications were utilized in a majority of JET patients (89%), and of those, amiodarone was the most commonly reported effective agent (60%). Radiofrequency ablation was conducted in 17 patients and cryoablation in 27, with comparable success rates (82% radiofrequency vs. 85% cryoablation, p = 1.0). Atrioventricular junction ablation was required in 3% and pacemaker implantation in 14%. There were 4 (4%) deaths, all in patients presenting at age < or =6 months.Patients with nonpost-operative JET have a wide range of clinical presentations, with younger patients demonstrating higher morbidity and mortality. With current medical, ablative, and device therapies, the majority of patients have a good clinical outcome.

View details for DOI 10.1016/j.jacc.2008.11.019

View details for Web of Science ID 000263666800008

View details for PubMedID 19232902
Impact of Manufacturer Advisories and FDA Recalls of Implantable Cardioverter Defibrillator Generators in Pediatric and Congenital Heart Disease Patients JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Mahajan, T., Dubin, A. M., Atkins, D. L., Bradley, D. J., Shannon, K. M., Erickson, C. C., Franklin, W. H., Cecchin, F., Berul, C. I. 2008; 19 (12): 1270-1274
Abstract

Recalls of implantable cardioverter defibrillator (ICD) generators have affected many patients. No information is available regarding the impact specifically on pediatric and congenital heart disease (CHD) patients. This study was undertaken to determine implications of ICD manufacturers' advisories and recalls on children and CHD patients.The first part of this study involved single-center review of patients who underwent ICD placement between 2000 and 2005. Patients with ICDs affected by the 2005 advisories/recalls were reviewed for incidence of explantation, malfunction and complications. Secondly, members of the Pediatric and Congenital Electrophysiology Society (PACES) were queried for patients with affected devices, incidences of explantation, malfunction, and explant-related complications. Data were pooled for aggregate summary.Among 233 patients who underwent ICD implantation at our institution during the study period, 58 (25%) patients had advisory/recalled devices and 13 of 58 (22%) underwent explantation following 3.1 +/- 1.3 years implant duration. No defects were identified by the manufacturer. No patients experienced complications requiring reintervention or rehospitalization. Questionnaire responses were received from 22 PACES institutions, included 177 patients with affected devices, of which 76 (43%) were removed. One patient died from complications following revision, and 1 patient had complications requiring reoperation. Two explanted devices had loose headers; no other defects were discovered. Taken together, 2 of 89 explanted devices were defective, and 2 complications occurred from explantation.Advisories and recalls affect substantial numbers of pediatric and CHD patients. A significant proportion underwent explantation. Although complications are infrequent, there are important medical, psychosocial, and financial impacts associated with ICD replacement.

View details for DOI 10.1111/j.1540-8167.2008.01259.x

View details for Web of Science ID 000261204100013

View details for PubMedID 18691353
Cryoablation for atrioventricular nodal reentrant tachycardia in young patients: Predictors of recurrence PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Chanani, N. K., Chiesa, N. A., Dubin, A. M., Avasarala, K., Van Hare, G. F., Collins, K. K. 2008; 31 (9): 1152-1159
Abstract

Recurrence rates of atrioventricular nodal reentry tachycardia (AVNRT) after cryoablation continue to remain high despite excellent initial success rates. Our objective was to evaluate the clinical outcomes of cryoablation for AVNRT with the 4-mm and 6-mm tip cryoablation catheters in a young population and to elicit predictors of arrhythmia recurrence.We retrospectively reviewed all patients who underwent cryoablation for AVNRT at the UCSF/Stanford Pediatric Arrhythmia Center from January 2004 to February 2007.One hundred fifty-four patients (age 13.7 years (3.2-24.4)) underwent cryoablation for AVNRT of which 144 patients had inducible AVNRT (123 sustained and 21 nonsustained) and 10 had presumed AVNRT. Initial success was achieved in 95% (146/154), with no difference between the 4-mm (93%) and 6-mm (98%) cryoablation catheter tips (P = 0.15). There was no permanent atrioventricular (AV) block. Transient third-degree AV block occurred in nine patients (6%), with no difference between the 4-mm (4%) and 6-mm (9%) tip (P = 0.13). AVNRT recurrence was documented in 14% in a median time of 2.5 months (0.25-20). Recurrences were lower with the 6-mm (9%) versus the 4-mm (18%) tip, but this did not reach statistical significance (P = 0.16). With univariate analysis, a longer fluoroscopy time was the only significant factor associated with recurrence. Multivariate analysis failed to identify any significant predictor of AVNRT recurrence.Outcomes of cryoablation for AVNRT continue to be good without the complication of AV block. We could not identify any specific parameter associated with AVNRT recurrence. Further improvements in cryoablation technique will be necessary to reduce recurrences.

View details for Web of Science ID 000258785000012

View details for PubMedID 18834467
Results of a multicenter retrospective implantable cardioverter-defibrillator registry of pediatric and congenital heart disease patients JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Berul, C. I., Van Hare, G. F., Kertesz, N. J., Dubin, A. M., Cecchin, F., Collins, K. K., Cannon, B. C., Alexander, M. E., Triedman, J. K., Walsh, E. P., Friedman, R. A. 2008; 51 (17): 1685-1691
Abstract

We sought to determine the implications of implantable cardioverter-defibrillator (ICD) placement in children and patients with congenital heart disease (CHD).There is increasing frequency of ICD use in pediatric and CHD patients. Until recently, prospective registry enrollment of ICD patients was not available, and children and CHD patients account for only a small percentage of ICD recipients. Therefore, we retrospectively obtained collaborative data from 4 pediatric centers, aiming to identify implant characteristics, shock frequency, and complications in this unique population.Databases from 4 centers were collated in a blinded fashion. Demographic information, implant electrical parameters, appropriate and inappropriate shock data, and complications were recorded for all implants from 1992 to 2004.A total of 443 patients were included, with a median age of 16 years (range 0 to 54 years) and median weight of 61 kg (range 2 to 130 kg), with 69% having structural heart disease. The most common diagnoses were tetralogy of Fallot (19%) and hypertrophic cardiomyopathy (14%). Implant indication was primary prevention in 52%. Shock data were available on 409 patients, of whom 105 (26%) received appropriate shocks (mean 4 shocks/patient, range 1 to 29 shocks/patient). Inappropriate shocks occurred in 87 of 409 patients (21%), with a mean of 6 per patient (range 1 to 60), mainly attributable to lead failure (14%), sinus or atrial tachycardias (9%), and/or oversensing (4%).Children and CHD ICD recipients have significant appropriate and inappropriate shock frequencies. Optimizing programming, medical management, and compliance may diminish inappropriate shocks. Despite concerns regarding generator recalls, lead failure remains the major cause of inappropriate shocks, complications, and system malfunction in children. Prospective assessment of ICD usage in this population may identify additional important factors in pediatric and CHD patients.

View details for DOI 10.1016/j.jacc.2008.01.033

View details for Web of Science ID 000255300200009

View details for PubMedID 18436121
The effects of dexmedetomidine on cardiac electrophysiology in children ANESTHESIA AND ANALGESIA Hammer, G. B., Drover, D. R., Cao, H., Jackson, E., Williams, G. D., Ramamoorthy, C., Van Hare, G. F., Niksch, A., Dubin, A. M. 2008; 106 (1): 79-83
Abstract

Dexmedetomidine (DEX) is an alpha2-adrenergic agonist that is approved by the Food and Drug Administration for short-term (<24 h) sedation in adults. It is not approved for use in children. Nevertheless, the use of DEX for sedation and anesthesia in infants and children appears to be increasing. There are some concerns regarding the hemodynamic effects of the drug, including bradycardia, hypertension, and hypotension. No data regarding the effects of DEX on the cardiac conduction system are available. We therefore aimed to characterize the effects of DEX on cardiac conduction in pediatric patients.Twelve children between the ages of 5 and 17 yr undergoing electrophysiology study and ablation of supraventricular accessory pathways had hemodynamic and cardiac electrophysiologic variables measured before and during administration of DEX (1 microg/kg IV over 10 min followed by a 10-min continuous infusion of 0.7 microg x kg(-1) x h(-1)).Heart rate decreased while arterial blood pressure increased significantly after DEX administration. Sinus node function was significantly affected, as evidenced by an increase in sinus cycle length and sinus node recovery time. Atrioventricular nodal function was also depressed, as evidenced by Wenckeback cycle length prolongation and prolongation of PR interval.DEX significantly depressed sinus and atrioventricular nodal function in pediatric patients. Heart rate decreased and arterial blood pressure increased during administration of DEX. The use of DEX may not be desirable during electrophysiology study and may be associated with adverse effects in patients at risk for bradycardia or atrioventricular nodal block.

View details for DOI 10.1213/01.ane.0000297421.92857.4e

View details for Web of Science ID 000251824300015

View details for PubMedID 18165557
Right ventricular mechanical dyssynchrony in children with hypoplastic left heart syndrome JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Friedberg, M. K., Silverman, N. H., Dubin, A. M., Rosenthal, D. N. 2007; 20 (9): 1073-1079
Abstract

Mechanical dyssynchrony predicts response to cardiac resynchronization therapy in adults with heart failure. Children with hypoplastic left heart syndrome (HLHS) are susceptible to right ventricular (RV) failure; however, mechanical dyssynchrony has not been studied in this population with newly available methodologies. We investigated RV mechanical dyssynchrony in children with HLHS using vector velocity imaging.We used vector velocity imaging to quantify the SD of time to peak velocity, strain, and strain rate among 6 RV segments to define intraventricular RV synchrony in 16 children with HLHS and RV and left ventricular (LV) synchrony in 16 healthy age-matched control subjects. We further investigated relations between QRS duration and mechanical dyssynchrony and between mechanical dyssynchrony and systolic function.Children with HLHS had significant RV mechanical dyssynchrony versus LV and RV control subjects (strain 37 +/- 35 vs 8 +/- 8 milliseconds, P = .003 [LV], 9 +/- 11 milliseconds, P = .005 [RV]; strain rate 31 +/- 37 vs 10 +/- 13 milliseconds, P = .04 [LV], 14 +/- 15 milliseconds, P = .09 [RV]). There was no significant relationship between QRS duration and mechanical dyssynchrony and no obvious relation between the degree of mechanical dyssynchrony and the RV fractional area of change.Children with HLHS have RV mechanical dyssynchrony unrelated to surface electrocardiographic QRS duration. This may contribute to RV dysfunction and may indicate the usefulness of cardiac resynchronization therapy in this population.

View details for DOI 10.1016/j.echo.2007.02.015

View details for Web of Science ID 000249454900007

View details for PubMedID 17566698
Mechanical dyssynchrony in children with systolic dysfunction secondary to cardiomyopathy: A Doppler tissue and vector velocity imaging study JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Friedberg, M. K., Silverman, N. H., Dubin, A. M., Rosenthal, D. N. 2007; 20 (6): 756-763
Abstract

Mechanical dyssynchrony is common in adults with heart failure and its presence predicts response to cardiac resynchronization therapy. However, mechanical dyssynchrony and its quantification by echocardiography have not been extensively studied in children with cardiomyopathy. We investigated mechanical dyssynchrony in children with systolic dysfunction secondary to cardiomyopathy using Doppler tissue imaging (DTI) and vector velocity imaging (VVI).We used DTI and VVI to quantify mechanical dyssynchrony in 22 children with systolic dysfunction secondary to cardiomyopathy and in 25 healthy control subjects. We analyzed DTI results corrected for cardiac dimensions and evaluated correlation between electrical and mechanical dyssynchrony and between mechanical dyssynchrony and systolic function.DTI and VVI revealed significant mechanical dyssynchrony among children with cardiomyopathy. Intraventricular and interventricular delays as defined by DTI, and the SD of time to peak velocity, strain, and strain rate as defined by VVI were 2 to 3 times higher in patients with cardiomyopathy as compared with control subjects. There was no significant relationship between electrical and mechanical dyssynchrony.Children with systolic dysfunction secondary to cardiomyopathy have mechanical dyssynchrony, unrelated to electrical dyssynchrony, which can be measured by recent echocardiographic techniques including DTI and VVI. Children with cardiomyopathy and mechanical dyssynchrony are potential candidates for cardiac resynchronization therapy.

View details for DOI 10.1016/j.echo.2006.11.007

View details for Web of Science ID 000247090900012

View details for PubMedID 17543748
Cryoablation of accessory pathways in the coronary sinus in young patients: A multicenter study from the Pediatric and Congenital Electrophysiology Society's Working Group on Cryoablation JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Collins, K. K., Rhee, E. K., Kirsh, J. A., Cannon, B. C., Fish, F. A., Dubin, A. M., Van Hare, G. F. 2007; 18 (6): 592-597
Abstract

This is a multicenter retrospective study evaluating the immediate- and mid-term outcomes of cryoablation of accessory pathways in the coronary sinus in children or in patients with congenital heart disease.Twenty-one patients (median age 13.0 years, range 2-40) from six institutions were included. The accessory pathways were concealed in 11 and manifest in 10. Of 12 patients who had coronary sinus angiography, two had large coronary sinus diverticula, one had a dilated coronary sinus due to a left superior vena cava to coronary sinus, and one had a "pouch" at the mouth of the coronary sinus. Six patients underwent ablation procedures with cryoablation alone, while in the remaining 15 patients, both cryoablation and radiofrequency ablation were utilized. The ablation procedure included left-sided endocardial mapping via a retrograde or transseptal approach in 13 (62%). Procedural success was achieved with cryoablation in the coronary sinus in 15/21 (71%). Four patients (19%) had successful radiofrequency ablation at the right or left posterior septum. Two patients (10%) had unsuccessful procedures. Of the 15 patients with initially successful cryoablation procedures, six (40%) had arrhythmia recurrences at a median of 17 days (range 1-120). Recurrences could not be explained by differences in patient or procedural variables.Cryoablation in the coronary venous system in young patients is feasible but associated with a high arrhythmia recurrence rate. Cryoablation techniques and/or equipment need to be improved in order to safely create more permanent lesions in this arrhythmia substrate.

View details for DOI 10.1111/j.1540-8167.2007.00831.x

View details for Web of Science ID 000246685400003

View details for PubMedID 17472717
Electrophysiological interventions for treatment of congestive heart failure in pediatrics and congenital heart disease. Expert review of cardiovascular therapy Dubin, A. M., Berul, C. I. 2007; 5 (1): 111-118
Abstract

Heart failure therapy, while well tested in the adult population, therapeutic interventions are less well defined in the pediatric population. Several treatment strategies are available for the adult patient with heart failure, thought few of these therapies have been proven in children. Morbidity and mortality in the pediatric population with a failing heart is significant, and rhythm management as well as strategies to improve hemodynamics are important in the care of these children. This review will address issues of rhythm management and resynchronization therapy in pediatric and congenital heart disease patients with heart failure.

View details for PubMedID 17187462
Rhythm management in pediatric heart failure. Congenital heart disease Berul, C. I., Dubin, A. M. 2006; 1 (4): 140-147
Abstract

There are several options now available for the management of arrhythmias and ventricular dysfunction in pediatric patients with heart failure. A hybrid approach that combines the expertise of heart failure and electrophysiology specialists may be well suited for the optimal management of these complex patients. Medical and device therapies may be synergistic in decreasing the morbidity and mortality in pediatric heart failure. Pediatric electrophysiology can now potentially offer therapies that can help prevent both arrhythmic and pump failure deaths, as well as improve functional capacity and quality of life. These therapies and the available supporting data relevant to pediatrics will be the focus of this review.

View details for DOI 10.1111/j.1747-0803.2006.00025.x

View details for PubMedID 18377538
Characterizing dual atrioventricular nodal physiology in pediatric patients with atrioventricular nodal reentrant tachycardia JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Blurton, D. J., Dubin, A. M., Chiesa, N. A., Van Hare, G. F., Collins, K. K. 2006; 17 (6): 638-644
Abstract

Dual atrioventricular (AV) nodal physiology, defined as an AH jump > or =50 msec with a 10 msec decrease in A1A2, is the substrate for atrioventricular nodal reentrant tachycardia (AVNRT) and yet it is present in a minority of pediatric patients with AVNRT. Our objective was to characterize dual AV nodal physiology as it pertains to a pediatric population.We retrospectively reviewed invasive electrophysiology studies in 92 patients with AVNRT (age12.1 +/- 3.7 yrs) and in 46 controls without AVNRT (age 13.3 +/- 3.7 yrs). Diagnoses in controls: syncope (N = 31), palpitations (N = 6), atrial flutter (N = 3), history of atrial tachycardia with no inducible arrhythmia (N = 3), and ventricular tachycardia (N = 3). General anesthesia was used in 49% of AVNRT and 52% of controls, P = 0.86. There were no differences in PR, AH, HV, or AV block cycle length. With A1A2 atrial stimulation, AVNRT patients had a significantly longer maximum AH achieved (324 +/- 104 msec vs 255 +/- 67 msec, P = 0.001), and a shorter AVNERP (276 +/- 49 msec vs 313 +/- 68 msec P = 0.0005). An AH jump > or =50 msec was found in 42% of AVNRT versus 30% of controls (P = 0.2). Using a ROC graph we found that an AH jump of any size is a poor predictor of AVNRT. With atrial overdrive pacing, PR > or = RR was seen more commonly in AVNRT versus controls, (55/91(60%) vs 6/46 (13%) P = 0.000).Neither the common definition of dual AV nodes or redefining an AH jump as some value <50 msec are reliable methods to define dual AV nodes or to predict AVNRT in pediatric patients. PR > or = RR is a relatively good predictor of AVNRT.

View details for DOI 10.1111/j.1540-8167.2006.00452.x

View details for Web of Science ID 000237740000014

View details for PubMedID 16836714
Risk stratification in the asymptomatic child with Wolff-Parkinson-White syndrome CURRENT OPINION IN CARDIOLOGY Niksch, A. L., Dubin, A. M. 2006; 21 (3): 205-207
Abstract

As the safety and efficacy of invasive electrophysiologic studies and ablation therapy in pediatrics improves, there has been a greater interest in developing adequate risk stratification criteria for the asymptomatic pediatric patient with Wolff-Parkinson-White syndrome. This review will discuss the recent literature regarding this debate.Recent retrospective and prospective studies of Wolff-Parkinson-White syndrome in asymptomatic pediatric patients have shown that the well established adult criteria for risk stratification may not be applicable in children. Both symptomatic and asymptomatic children had similar accessory pathway effective refractory periods and supraventricular tachycardia inducibility in recent invasive electrophysiologic studies. The first attempt at prospective evaluation of the use of ablation therapy in asymptomatic adult and pediatric patients with the condition has sparked a debate as to the definition of a high-risk patient and the utility of ablation in the asymptomatic patient.It is still controversial whether the established criteria for risk stratification in adults can be confidently applied to the pediatric patient. The majority of pediatric electrophysiologists use invasive electrophysiologic studies for risk stratification and selection of appropriate therapy. This clinical practice reflects the increasing prevalence and safety of electrophysiologic study and ablation. Further studies to better define indications for study and ablation are still necessary, however, to define accurate criteria for risk stratification in this difficult pediatric problem.

View details for Web of Science ID 000237588500009

View details for PubMedID 16601458
Cryoablation in pediatric atrioventricular nodal reentry: Electrophysiologic effects on atrioventricular nodal conduction HEART RHYTHM Collins, K. K., Dubin, A. M., Chiesa, N. A., McDaniel, G. M., Van Hare, G. F. 2006; 3 (5): 557-563
Abstract

Cryoablation for treatment of atrioventricular nodal reentrant tachycardia (AVNRT) is safe and efficacious. Information on the effects of cryoablation on atrioventricular (AV) nodal conduction is limited.The purpose of this study was to evaluate the effects of cryoablation on AV nodal conduction in pediatric patients with AVNRT.We retrospectively analyzed electrophysiologic studies before and after successful cryoablation. Patients were divided into two groups: group 1 (n = 22, age 14 +/- 3 years) had baseline discontinuous atrial-to-His interval (AH) conduction curves; and group 2 (n = 13, age 12 +/- 4 years, P = .054) had continuous curves.At baseline, group 1 had longer measurements of maximal AH with A1A2, AV nodal effective refractory period, and AV block cycle length. Postcryoablation, both group 1 and group 2 showed decreases in maximal AH with A1A2 pacing or atrial overdrive pacing and in the finding of PR > or = RR with atrial overdrive pacing (group 1: 55% vs 5%, P < .001; group 2: 69% vs 0%, P < .001). A significant increase in overall AV effective refractory period and a decrease in AV block cycle length were found in group 1 but not group 2. Fifty percent of group 1 patients had complete abolition of slow pathway conduction.Successful cryoablation for treatment of AVNRT is associated with a reduction in PR > or = RR and with decreases in maximal AH with A1A2 pacing or atrial overdrive pacing. Further study is needed to determine the usefulness of these parameters for assessment of ablation efficacy or as proxies for AVNRT inducibility.

View details for DOI 10.1016/j.hrthm.2006.01.018

View details for Web of Science ID 000237577200010

View details for PubMedID 16648061
Cryoablation versus radiofrequency ablation for treatment of pediatric atrioventricular nodal reentrant tachycardia: Initial experience with 4-mm cryocatheter HEART RHYTHM Collins, K. K., Dubin, A. M., Chiesa, N. A., Avasarala, K., Van Hare, G. F. 2006; 3 (5): 564-570
Abstract

Initial reports have shown cryoablation to be safe and efficacious for treatment of atrioventricular nodal reentrant tachycardia (AVNRT). No direct comparisons of cryoablation vs radiofrequency (RF) catheter ablation in pediatric patients have been made.The purpose of this study was to compare the outcomes of cryothermal vs RF catheter ablation for treatment of AVNRT in pediatric patients.We retrospectively reviewed consecutive ablation procedures for treatment of AVNRT at a single arrhythmia center. The RF group consisted of patients who underwent RF ablation from 2002 until cryothermy became available. The cryoablation group consisted of patients who underwent cryothermal ablation from 2004 to 2005. The groups were compared for procedural and electrophysiologic outcomes.RF (n = 60, age 14 +/- 4 years) and cryoablation (n = 57, age 14 +/- 4 years) groups had similar demographic and baseline parameters. Procedural times were shorter in the RF group (RF ablation 112 +/- 31 minutes vs cryoablation 148 +/- 46 minutes, P < .001). Fluoroscopy times were comparable (RF ablation 21 +/- 15 minutes vs cryoablation 20 +/- 13 minutes, P = .77). In an intention-to-treat analysis, success of the procedure was 100% for RF ablation and 95% for cryoablation (P = .11). No permanent AV block occurred in either group. Recurrence rates were higher for the cryoablation group, but this did not reach statistical significance (RF ablation 2% vs cryoablation 8%, P = .19).Cryoablation appears to be similar to RF for ablation of AVNRT with respect to short-term efficacy and safety of the procedure in a pediatric population. Recurrence rates are higher with cryoablation.

View details for DOI 10.1016/j.hrthm.2006.01.026

View details for Web of Science ID 000237577200011

View details for PubMedID 16648062
Effect of targeted deletions of beta(1)- and beta(2)-adrenergic-receptor subtypes on heart rate variability AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Ecker, P. M., Lin, C. C., Powers, J., Kobilka, B. K., Dubin, A. M., Bernstein, D. 2006; 290 (1): H192-H199
Abstract

Beta-adrenergic receptors (beta-ARs) play a major role in regulating heart rate (HR) and contractility in the intact cardiovascular system. Three subtypes (beta1, beta2, and beta3) are expressed in heart tissue, and the role of each subtype in regulating cardiac function has previously been determined by using both pharmacological and gene-targeting approaches. However, previous studies have only examined the role of beta-ARs in the macrolevel regulation of HR. We employed three knockout (KO) mouse lines, beta1-KO, beta2-KO, and beta1/beta2 double KO (DL-KO), to examine the role that beta-AR subtypes play in HR variability (HRV) and in the sympathetic and parasympathetic inputs into HR control. Fast Fourier transformation (FFT) in frequency domain methods of ECG spectral analysis was used to resolve HRV into high- and low-frequency (HF and LF) powers. Resting HR (in beats/min) was decreased in beta1-KO [488 (SD 27)] and DL-KO [495 (SD 12)] mice compared with wild-type [WT; 638 (SD 30)] or beta2-KO [656 (SD 51)] (P < 0.0005) mice. Mice lacking beta1-ARs (beta1-KO and DL-KO) had increased HRV (as illustrated by the standard deviation of normal R-R intervals) and increased normalized HF and LF powers compared with mice with intact beta1-ARs (WT and beta2-KO). These results demonstrate the differential role of beta-AR subtypes in regulating autonomic signaling.

View details for DOI 10.1152/ajpheart.00032.2005

View details for Web of Science ID 000234148200023

View details for PubMedID 16113068
A multicenter experience with novel implantable cardioverter defibrillator configurations in the pediatric and congenital heart disease population JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Stephenson, E. A., Batra, A. S., Knilans, T. K., Gow, R. M., Gradaus, R., Balaji, S., Dubin, A. M., Rhee, E. K., Ro, P. S., Thogersen, A. M., Cecchin, F., Triedman, J. K., Walsh, E. P., Berul, C. I. 2006; 17 (1): 41-46
Abstract

In pediatric and congenital heart disease patients, transvenous ICD implantation may be limited secondary to patient size, venous, or cardiac anatomy. Epicardial patches require a thoracotomy, and may lead to a restrictive pericardial process. Because of these issues, we have explored novel ICD configurations.Retrospective review at 10 centers implanting ICDs without a transvenous shocking coil or epicardial patches.Twenty-two patients underwent implant at a mean age of 8.9 years (range: 0.3-43.5), with a mean weight of 25.5 kg (range: 5.2-70). Diagnoses included complex CHD, intracardiac tumors, cardiomyopathy, idiopathic VT, LV noncompaction, and long QT syndrome. Three configurations were used: subcutaneous array, a transvenous design ICD lead placed on the epicardium, or a transvenous design ICD lead placed subcutaneously. Difficulties were found at implant in 8 patients: 4 had difficulty inducing VT/VF, and 4 had high DFTs. Over a mean follow-up of 2.2 years (range: 0.2-10.5), 7 patients had appropriate shocks. Inappropriate shocks occurred in 4 patients. System revisions were required in 7 patients: 2 generator changes (in 1 patient), 3 pace-sense lead replacement, 1 additional subcutaneous coil placement due to increased DFT, 1 upgrade to a transvenous system, and 1 revision to epicardial patch system.ICD implantation can be performed without epicardial patches or transvenous high-energy leads in this population, using individualized techniques. This will allow ICD use in patients who have intracardiac shunting or are deemed too small for transvenous ICD leads. The long-term outcome and possible complications are as yet unknown in this population, and they should be monitored closely with follow-up DFTs.

View details for DOI 10.1111/j.1540-8167.2005.00271.x

View details for Web of Science ID 000234527200009

View details for PubMedID 16426398
Resynchronization therapy in pediatric and congenital heart disease patients - An international multicenter study JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Dubin, A. M., Janousek, J., Rhee, E., Strieper, M. J., Cecchin, F., Law, I. H., Shannon, K. M., Temple, J., Rosenthal, E., Zimmerman, F. J., Davis, A., Karpawich, P. P., Al Ahmad, A., Vetter, V. L., Kertesz, N. J., Shah, M., Snyder, C., Stephenson, E., Emmel, M., Sanatani, S., Kanter, R., Batra, A., Collins, K. K. 2005; 46 (12): 2277-2283
Abstract

Our objective was to evaluate the short-term safety and efficacy of cardiac resynchronization therapy (CRT) in children.Cardiac resynchronization therapy has been beneficial for adult patients with poor left ventricular function and intraventricular conduction delay. The efficacy of this therapy in the young and in those with congenital heart disease (CHD) has not yet been established.This is a multi-center, retrospective evaluation of CRT in 103 patients from 22 institutions.Median age at time of implantation was 12.8 years (3 months to 55.4 years). Median duration of follow-up was four months (22 days to 1 year). The diagnosis was CHD in 73 patients (71%), cardiomyopathy in 16 (16%), and congenital complete atrioventricular block in 14 (13%). The QRS duration before pacing was 166.1 +/- 33.3 ms, which decreased after CRT by 37.7 +/- 30.7 ms (p < 0.01). Pre-CRT systemic ventricular ejection fraction (EF) was 26.2 +/- 11.6%. The EF increased by 12.8 +/- 12.7 EF units with a mean EF after CRT of 39.9 +/- 14.8% (p < 0.05). Of 18 patients who underwent CRT while listed for heart transplantation, 3 improved sufficiently to allow removal from the transplant waiting list, 5 underwent transplant, 2 died, and 8 others are currently awaiting transplant.Cardiac resynchronization therapy appears to offer benefit in pediatric and CHD patients who differ substantially from the adult populations in whom this therapy has been most thoroughly evaluated to date. Further studies looking at the long-term benefit of this therapy in this population are needed.

View details for DOI 10.1016/j.jacc.2005.05.096

View details for Web of Science ID 000234090600017

View details for PubMedID 16360058
The electrophysiology of atrioventricular nodal reentry tachycardia following the Mustard or Senning procedure and its radiofrequency ablation CARDIOLOGY IN THE YOUNG Greene, A. E., Skinner, J. R., Dubin, A. M., Collins, K. K., Van Hare, G. F. 2005; 15 (6): 611-616
Abstract

We describe the electrophysiological studies undertaken in four patients with atrioventricular nodal reentry tachycardia in the setting of concordant atrioventricular and discordant ventriculo-arterial connections (transposition). Radiofrequency ablation was attempted in three, all with success. Clear evidence of dual antegrade pathways through the atrioventricular node was present in only one of the four, but other characteristics of discrete fast and slow pathways into the atrioventricular node were present in all. Atrioventricular nodal reentry tachycardia was inducible in all. In the three patients in whom ablation was attempted, the application of radiofrequency energy to the low medial regions of the systemic venous atrium (morphologically left) consistently caused junctional accelerated rhythm, but these lesions were not successful in eliminating the tachycardia. Successful radiofrequency ablation required a retrograde approach to the region of the slow pathway in the pulmonary venous atrium (morphologically right).

View details for Web of Science ID 000235853900009

View details for PubMedID 16297255
Congenital junctional ectopic tachycardia and congenital complete atrioventricular block: A shared etiology? HEART RHYTHM Dubin, A. M., Cuneo, B. F., Strasburger, J. F., Wakai, R. T., Van Hare, G. F., Rosenthal, D. N. 2005; 2 (3): 313-315
View details for DOI 10.1016/j.hrthm.2004.11.016

View details for Web of Science ID 000227500000019

View details for PubMedID 15851326
Normal ECG limits for Asian infants and children COMPUTERS IN CARDIOLOGY 2005, VOL 32 Sun, K., Li, F., Zhou, Y., Dubin, A. M., Rautaharju, P. M., Liebman, J., Gregg, R. E., Helfenbein, E. D., Lindauer, J. M., Zhou, S. H. 2005; 32: 455-458
View details for Web of Science ID 000236378300115
International society for heart and lung transplantation: Practice guidelines for management of heart failure in children JOURNAL OF HEART AND LUNG TRANSPLANTATION Rosenthal, D., Chrisant, M. R., Edens, E., Mahony, L., Canter, C., Colan, S., Dubin, A., Lamour, J., Ross, R., Shaddy, R., Addonizio, L., Beerman, L., Berger, S., Bernstein, D., Blume, E., Boucek, M., Checchia, P., Dipchand, A., Drummond-Webb, J., Fricker, J., Friedman, R., Hallowell, S., Jaquiss, R., Mital, S., Pahl, E., Pearce, B., Rhodes, L., Rotondo, K., Rusconi, P., Scheel, J., Singh, T. P., Towbin, J. 2004; 23 (12): 1313-1333
View details for Web of Science ID 000226087100001

View details for PubMedID 15607659
Implantable cardioverter defibrillators in children. Expert review of cardiovascular therapy Chun, T. U., Collins, K. K., Dubin, A. M. 2004; 2 (4): 561-571
Abstract

The use of implantable cardioverter defibrillators in children presents several unique challenges for the pediatric cardiologist. Size considerations and hardware limitations are important in the current generation of devices that are not designed with children in mind. Defibrillator devices are used to prolong life, which may have significant implications for leads and electrodes that are affixed to the heart in a child who has continued growth potential. A greater number of children with congenital heart defects are surviving into adulthood, many of whom have a risk of late sudden death following repair. These patients may also have unique anatomic considerations that may affect device placement. This article will address some of the issues faced when considering the use of implantable-defibrillator therapy in the pediatric population.

View details for PubMedID 15225115
Validation of simulation-based training in neonatal resuscitation: Use of heart rate variability as marker for mental workload Murphy, A. A., Kaegi, D. M., Gobble, R., Dubin, A., Howard, S. K., Gaba, D. M., Sowb, Y. A., Halamek, L. P. NATURE PUBLISHING GROUP. 2004: 353A-353A
View details for Web of Science ID 000220591102074
Electrical resychronization of failing right ventricle - Response CIRCULATION Dubin, A. M., Feinstein, J. A., Van Hare, G. F., Rosenthal, D. N., Reddy, V. M., Hanley, F. L. 2004; 109 (2): E5-E5
View details for Web of Science ID 000188250500030
A multicenter experience with novel implantable cardioverter defibrillator configurations in the pediatric and congenital heart disease population Stephenson, E. A., Batra, A. S., Knilans, T. K., Gradaus, R., Balaji, S., Dubin, A. M., Rhee, E. K., Thogersen, A. M., Triedman, J. K., Walsh, E. P., Cecchin, F., Berul, C. I. LIPPINCOTT WILLIAMS & WILKINS. 2003: 494-494
View details for Web of Science ID 000186360602321
The use of Implantable cardioverter-defibrillators in pediatric patients awaiting heart transplantation JOURNAL OF CARDIAC FAILURE Dubin, A. M., Berul, C. I., Bevilacqua, L. M., Collins, K. K., Etheridge, S. P., Fenrich, A. L., Friedman, R. A., Hamilton, R. M., Schaffer, M. S., Shah, M., Silka, M. J., Van Hare, G. F., Kertesz, N. J. 2003; 9 (5): 375-379
Abstract

This multicenter study evaluated experience with implantable cardioverter defibrillators (ICD) as a bridge to orthotopic heart transplantation (OHT) in children.The application of ICD therapy continues to expand in pediatric populations, due in part to improved technology and new indications, including the prevention of sudden death while awaiting OHT.We performed a retrospective review of ICD databases at 9 pediatric transplant centers.Twenty-eight patients (16 males) underwent implantation or had a preexisting ICD while awaiting OHT between 1990 and 2002. The median age at implant was 14.3 years (11 months to 21 years) with a median weight of 49 kg (11.7-88 kg). Diagnoses included cardiomyopathy (n=22), and congenital heart disease (n=6). Indications for ICD implantation included ventricular tachycardia/fibrillation (n=23), syncope (n=5), aborted sudden death with no documentation of rhythm disturbance (n=5), ventricular ectopy (n=1), and poor function (n=5). Of the 28 ICDs, 23 were implanted by a transvenous approach and 5 by epicardial route. There were 55 defibrillator discharges in 17 patients, 47 (85%) of which (in 13 patients) were appropriate. The 8 inappropriate discharges (in 6 patients) were triggered by sinus tachycardia, inappropriate sensing, and atrial flutter. The mean time from implantation to first appropriate shock was 6.9 months (1 day to 2.6 years). Twenty-one patients underwent transplantation during the study period, whereas 2 died while awaiting a donor. Morbidity included a lead fracture, 3 episodes of electromechanical dissociation, and 1 episode of electrical storm.ICD implantation represents an effective bridge to transplantation in pediatric patients. The complication rate is low, with inappropriate device discharge due primarily to sinus tachycardia or atrial flutter. There is a high incidence of appropriate ICD therapy for malignant ventricular arrhythmias in this highly selected group of patients.

View details for DOI 10.1054/s1071-9164(03)00128-3

View details for Web of Science ID 000186326500006

View details for PubMedID 14583898
Atrial tachyarrhythmias and permanent pacing after pediatric heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Collins, K. K., Thiagarajan, R. R., Chin, C., Dubin, A. M., Van Hare, G. F., Robbins, R. C., Bernstein, D., Berul, C. I., Blume, E. D. 2003; 22 (10): 1126-1133
Abstract

Atrial tachyarrhythmias have been reported in as high as 50% of adult heart recipients. Limited information is available on arrhythmias in pediatric transplant patients. Our objective was to determine the prevalence and significance of atrial tachyarrhythmias and permanent pacing following pediatric heart transplantation.A retrospective review of the medical records, electrocardiograms, and Holter recordings of all consecutive patients following heart transplantation at Children's Hospital, Boston (n = 104) and Lucile Packard Children's Hospital, Stanford (n = 123) was performed. The study group consisted of 227 patients with a median age at transplant of 10.2 yrs (1 day-23.3 yrs).Atrial tachyarrhythmias occurred in 32 patients (14%) at a median of 15 days post-transplant (1 day-9.2 yrs) and included atrial flutter (n = 13), atrial fibrillation (n = 7), ectopic atrial tachycardia (n = 5), atrioventricular reciprocating tachycardia or atrioventricular node reentry (n = 5), and other (n = 2). Atrial flutter was the only tachyarrhythmia associated with allograft rejection (6/13 atrial flutter vs. 0/7 atrial fibrillation vs. 0/5 ectopic atrial tachycardia, p = 0.03). Patients with atrial fibrillation had a 2.5 fold (95%CI 1.7-3.5) higher risk of death or retransplant compared to patients without atrial fibrillation. Ectopic atrial tachycardia tended to occur in younger recipients compared to atrial fibrillation and flutter (2.7 yrs vs 18.6 yrs and 8.5 yrs respectively, p = 0.06) and was associated with a benign clinical course. There was no association between atrial tachyarrhythmias and graft ischemic time, surgical technique, or coronary artery disease. Pacemakers were required in 12 patients (5.2%), 7 with sinus node dysfunction and 5 for intermittent complete atrioventricular block. There was no consistent association between the need for permanent pacing and coronary artery disease, rejection, or surgical technique.Atrial tachyarrhythmias and permanent pacing were uncommon in this cohort of pediatric heart transplant recipients. Association with cardiac rejection, clinical course, and mortality varied depending on the tachyarrhythmia mechanism.

View details for DOI 10.1016/S1053-2498(02)01193-2

View details for Web of Science ID 000185764400007

View details for PubMedID 14550822
Detecting and diagnosing arrhythmias in adults with congenital heart disease. Current cardiology reports Collins, K. K., Dubin, A. M. 2003; 5 (4): 331-335
Abstract

Arrhythmias are a major cause of morbidity and mortality in adults with congenital heart disease; they can range from occult asymptomatic sinus node disease to sudden death. Detecting and diagnosing these arrhythmias presents a challenge when caring for these patients. A high index of suspicion is necessary, as well as a thorough understanding of the underlying heart defect and subsequent surgical interventions. A careful history, noninvasive evaluation, and in some cases invasive testing are all necessary to determine arrhythmias in this population.

View details for PubMedID 12801455
Electrical resynchronization - A novel therapy for the failing right ventricle CIRCULATION Dubin, A. M., Feinstein, J. A., Reddy, V. M., Hanley, F. L., Van Hare, G. F., Rosenthal, D. N. 2003; 107 (18): 2287-2289
Abstract

Many patients with congenital heart disease develop right ventricular (RV) failure due to anatomy and prior therapy. RV problems may include right bundle-branch block (RBBB), volume loading, and chamber enlargement. Because the failing RV may have regional dyskinesis, we hypothesized that resynchronization therapy might augment its performance.We studied 7 patients with RV dysfunction and RBBB, using a predefined pacing protocol. QRS duration, cardiac index (CI), and RV dP/dt were measured in 4 different pacing states. Atrioventricular pacing improved CI and RV dP/dtmax and decreased QRS duration as compared with atrial pacing or sinus rhythm.Atrioventricular pacing in patients with RBBB and RV dysfunction augments RV and systemic performance. RV resynchronization is a promising novel therapy for patients with RV failure.

View details for DOI 10.1161/01.CIR.0000070930.33499.9F

View details for Web of Science ID 000182807000014

View details for PubMedID 12732607
Effect of position on sleep, heart rate variability, and QT interval in preterm infants at 1 and 3 months' corrected age PEDIATRICS Ariagno, R. L., Mirmiran, M., Adams, M. M., Saporito, A. G., Dubin, A. M., Baldwin, R. B. 2003; 111 (3): 622-625
Abstract

Prone sleeping position has a strong link to sudden infant death syndrome (SIDS), and the "Back to Sleep" campaign has played an important role in reducing SIDS. We tested the hypothesis that the mechanism of the sleep position effect is based on changes in sleep, arousal, heart rate variability (HRV), and the QT interval of the electrocardiogram.We studied 16 premature infants longitudinally, at 1 and 3 months' corrected age. Videosomnography recordings were made during the infants' normal daytime naps. Each infant was recorded in both supine and prone positions. The recordings were analyzed in 30-second epochs, which were classified as awake, active sleep (AS), quiet sleep (QS), or indeterminate sleep. Electrocardiogram data were sampled with an accuracy of 1 millisecond. Time domain analysis of HRV was measured by standard deviation of all R-R intervals and by the square root of the mean of the sum of the squares of the differences between adjacent R-R intervals. Frequency domain analysis was done for low frequency (0.04-0.14 Hz) and high frequency (0.15-0.5 Hz) HRV. We measured QT, JT, and R-R intervals during AS and QS for each position.We found no significant differences between supine and prone position, either in total sleep time or in percentage of QS. Percentage of AS was significantly lower in the supine position, but only at 1 month corrected age. The incidence of short, spontaneous, sleep transitions was significantly higher in supine, also only at 1 month corrected age. Time domain analysis of HRV showed a significantly lower variability in prone, but only during QS. Frequency domain analysis of HRV showed no differences between the 2 sleeping positions. Both QT and JT intervals were significantly longer in prone during QS, but only at 1 month corrected age.Despite the commonly held belief, prone position did not substantially increase total sleep at these ages. On the other hand, prone sleeping decreased the number of sleep transitions at 1 month corrected age, increased QT and JT intervals, and reduced HRV, thereby potentially increasing the vulnerability for SIDS. This study supports "Back to Sleep" as the position of choice not only for term but also for preterm infants after discharge home.

View details for Web of Science ID 000181294000044

View details for PubMedID 12612246
Survey of current practice of pediatric electrophysiologists for asymptomatic Wolff-Parkinson-White syndrome PEDIATRICS Campbell, R. M., Strieper, M. J., Frias, P. A., Collins, K. K., Van Hare, G. F., Dubin, A. M. 2003; 111 (3)
Abstract

To determine the approach that pediatric electrophysiologists use as they evaluate asymptomatic patients with Wolff-Parkinson-White (WPW) syndrome regarding electrophysiologic testing and radio frequency ablation.A 21-question survey was mailed to 66 pediatric electrophysiologists who had voluntarily submitted patient data at any time to the Pediatric Radio Frequency Ablation Registry since its inception in 1990. The survey addressed issues regarding physician experience with electrophysiologic testing and radio frequency ablation, risk assessment, electrophysiology study, and factors that influence the decision to perform radio frequency ablation in asymptomatic patients.Returned surveys (43 of 66 [65%]) were analyzed blindly. The 43 physicians who responded were experienced, with 37 reporting >5 years of performing radio frequency ablation and 30 having performed >200 radio frequency ablation procedures. Thirty-six of the 43 electrophysiologists used invasive electrophysiologic study for risk stratification in asymptomatic patients with WPW. Electrophysiologic findings guided selection of patients for radio frequency ablation procedures. Expected radio frequency ablation outcome quotes to the family were consistent with recently published data from the Electrophysiology Society regarding current-era experience with radio frequency ablation.The majority of responding electrophysiologists use invasive electrophysiologic study both to stratify risk for asymptomatic WPW and to select appropriate patients for radio frequency ablation. This current practice should be communicated to other pediatric cardiologists and pediatricians.

View details for Web of Science ID 000181294000009

View details for PubMedID 12612279
Circadian and seasonal variation of malignant Arrhythmias in a pediatric and congenital heart disease population JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Stephenson, E. A., Collins, K. K., Dubin, A. M., Epstein, M. R., Hamilton, R. M., Kertesz, N. J., Alexander, M. E., Cecchin, F., Triedman, J. K., Walsh, E. P., Berul, C. I. 2002; 13 (10): 1009-1014
Abstract

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.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.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.

View details for Web of Science ID 000178934500010

View details for PubMedID 12435187
Validation of the Doppler PR interval in the fetus JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Rosenthal, D., Friedman, D. M., Buyon, J., Dubin, A. 2002; 15 (9): 1029-1030
View details for DOI 10.1067/mje.2002.121438

View details for Web of Science ID 000178119200034

View details for PubMedID 12221431
Use of electrophysiologic testing to assess risk in children with Wolff-Parkinson-White syndrome CARDIOLOGY IN THE YOUNG Dubin, A. M., Collins, K. K., Chiesa, N., Hanisch, D., Van Hare, G. F. 2002; 12 (3): 248-252
Abstract

In adults with Wolff-Parkinson-White syndrome, the likelihood of sudden death can be estimated based upon the presence or absence of symptoms. Comparable data in children do not exist. To date, therefore, invasive risk stratification has been used to guide management regarding radiofrequency ablation in symptomatic children. As the safety of electrophysiology study and radiofrequency ablation in children has improved, asymptomatic patients have been referred more commonly for invasive risk stratification. We sought to compare the findings from electrophysiologic studies in symptomatic children with Wolff-Parkinson-White syndrome to the findings in asymptomatic children with Wolff-Parkinson-White pattern on their electrocardiogram. Thus, we compared the findings from electrophysiologic studies carried out in patients seen at Stanford University and University of California, San Francisco, from April 1999 to February 2001 with a preexcitation pattern on their electrocardiogram. The patients were divided into three groups: 23 asymptomatic patients studied for risk stratification, 19 patients who presented with syncope, and 77 patients presenting with documented supraventricular tachycardia. Data were collected for commonly accepted invasive criterions for stratification of risk: an effective refractory period of the accessory pathway less than 270 ms, multiple pathways, septal location of pathway, and inducibility of supraventricular tachycardia. Groups were compared by chi-square. No differences were found between the groups for any of the variables. These data suggest that risk factors for sudden death, developed in studies of adult patients, are not clearly applicable to children. Further studies are needed better to define the indications for study and ablation in children.

View details for Web of Science ID 000176685800008

View details for PubMedID 12365171
Clinical outcomes of children with normal cardiac anatomy having radiofrequency catheter ablation >= 10 years earlier AMERICAN JOURNAL OF CARDIOLOGY Collins, K. K., Chiesa, N. A., Dubin, A. M., Van Hare, G. F. 2002; 89 (4): 471-?
View details for Web of Science ID 000173816400025

View details for PubMedID 11835935
Invasive electrophysiology in children: State of the art JOURNAL OF ELECTROCARDIOLOGY Van Hare, G. F., Dubin, A. M., Collins, K. K. 2002; 35: 165-174
Abstract

While noninvasive techniques, including esophageal recording and pacing, clearly have advantages in the pediatric population; they also have significant limitations. Invasive electrophysiology (EP) in children now encompasses the use of many advanced engineering applications, which contribute to the efficacy of such procedures. This is particularly true with respect to the performance of radiofrequency catheter ablation. First, microcatheters (eg, Cardima) offer advantages as diagnostic catheters in small hearts, and allow pacing and recording from both atrium and ventricle in even the smallest infants using limited venous access. In addition, there is the possibility of mapping the distal coronary sinus, and the right atrioventricular groove via the right coronary artery. Second, electroanatomic mapping using the CARTO system (Biosense Webster) allows complex maps to be constructed in patients with congenital heart disease and a history of cardiac surgery. Although somewhat laborious to construct, such maps offer great detail to guide ablation, and also provide voltage information to guide identification of patches and scars. Similarly, non-contact mapping systems (eg, EnSite, Endocardial Solutions) are available which record far-field potentials and employ solutions to the inverse problem to reconstruct endocardial potentials. Three-dimensional mapping based on a single beat is possible, and the success of ablation in creating conduction block in unique channels can be evaluated. Both of these three-dimensional mapping systems have the potential to improve outcomes in patients with complex disease undergoing ablation. Finally, patients are now undergoing combined procedures with interventional catheterization (eg, device closure, stenting) along with EP procedures (eg, ablation, device implant) in the same laboratory session. The state of the art in invasive pediatric EP increasingly involves the use of advanced technology adapted for use in pediatric and congenital heart disease applications.

View details for DOI 10.1054/jelc.2002.37175

View details for Web of Science ID 000180263200024

View details for PubMedID 12539115
Spectrum and progression of conduction abnormalities in infants born to mothers with anti-SSA/Ro-SSB/La antibodies LUPUS Askanase, A. D., Friedman, D. M., Copel, J., Dische, M. R., Dubin, A., Starc, T. J., Katholi, M. C., Buyon, J. P. 2002; 11 (3): 145-151
Abstract

The classic cardiac manifestation of neonatal lupus is congenital heart block, attributed to antibody-mediated inflammation and subsequent fibrosis of the atrioventricular (AV) node. In considering the pathologic process of injury it may be that tissue damage results in a range of conduction abnormalities. Identification of less-advanced degrees of block or of fibrosis around the AV node without any conduction abnormality on EKG would support this pathologic model, and serve as a potential marker for treatment if the conduction defect could be shown to progress. To ascertain the spectrum of arrhythmias associated with maternal anti-SSA/Ro-SSB/La antibodies, records of all children enrolled in the Research Registry for Neonatal Lupus were reviewed. Of 187 children with congenital heart block whose mothers have anti-SSA/Ro-SSB/La antibodies, nine had a prolonged PR interval on EKG at birth, four of whom progressed to more advanced AV block. A child whose younger sibling had third degree block was diagnosed with first degree block at age 10 years at the time of surgery for a broken wrist. Two children diagnosed in utero with second degree block were treated with dexamethasone and reverted to normal sinus rhythm by birth, but ultimately progressed to third degree block. Four children had second degree block at birth: of these, two progressed to third degree block. Sinus bradycardia (< 100 bpm) was present in three (3.8%) of 78 fetuses for whom atrial rates were recorded by echocardiogram. Of 40 neonates for whom EKGs were available, the mean atrial rate was 137+/-20 bpm (range 75-200). These data have important research and clinical implications. In contrast to the AV node, permanent sinoatrial nodal involvement is not clinically apparent. Perhaps many fetuses sustain mild inflammation, but resolution is variable, as suggested by the presence of incomplete AV block. Since subsequent progression of less-advanced degrees of block can occur, an EKG should be performed on all infants born to mothers with anti-SSA/Ro-SSB/La antibodies.

View details for Web of Science ID 000174970800003

View details for PubMedID 11999879
Atrial arrhythmias and conduction abnormalities in pediatric heart transplantation Collins, K. K., Thiagarajan, R. R., Chin, C., Dubin, A. M., Bernstein, D., Robbins, R. C., Van Hare, G. F., Mayer, J. E., Berul, C. I., Blume, E. D. LIPPINCOTT WILLIAMS & WILKINS. 2001: 745-745
View details for Web of Science ID 000171895003488
Effect of targeted deletions of beta-1 and beta-2 adrenergic receptor (AR) subtypes on heart rate variability (HRV) Lin, C. C., Ecker, P., Powers, J., Kobilka, B. K., Dubin, A. M. LIPPINCOTT WILLIAMS & WILKINS. 2001: 322-322
View details for Web of Science ID 000171895001539
Survey of current practices in use of amiodarone and implantable cardioverter defibrillators in pediatric patients with end-stage heart failure AMERICAN JOURNAL OF CARDIOLOGY Dubin, A. M., Van Hare, G. F., Collins, K. K., Bernstein, D., Rosenthal, D. N. 2001; 88 (7): 809-?
View details for Web of Science ID 000171374300022

View details for PubMedID 11589857
Reentrant tachycardia using two discrete atrioventricular nodes and a concealed atriofascicular pathway PEDIATRIC CARDIOLOGY Dubin, A. M., Desai, K., Van Hare, G. F. 2001; 22 (5): 400-402
Abstract

We describe a case of reentrant supraventricular tachycardia using two discrete atrioventricular (AV) nodes in the antegrade direction and a concealed atriofascicular pathway in the retrograde direction in a 21-year-old woman with superior-inferior ventricles and ventricular inversion. Using the Carto endocardial mapping system, two discrete AV nodes were identified as well as a separate decremental AV pathway located midway between the two nodes. Ablation of the separate pathway resulted in elimination of inducible tachycardia without loss of either AV node.

View details for Web of Science ID 000170650100007

View details for PubMedID 11526416
Cisapride associated with QTc prolongation in very low birth weight preterm infants PEDIATRICS Dubin, A., Kikkert, M., Mirmiran, M., Ariagno, R. 2001; 107 (6): 1313-1316
Abstract

No systematic study has been performed to evaluate the effect of cisapride on the QT interval in premature infants. Cisapride, which has recently been withdrawn by the Food and Drug Administration and is no longer an approved therapy, was commonly used for preterm infant care to improve the advance of enteral feedings and to reduce reflux and associated apnea. Our aim was to evaluate the effect of recommended doses of cisapride on the QT interval in this population.Prospective blinded evaluation of electrocardiogram for QT, JT, QTc, and JTc measurements in 25 preterm infants before and after cisapride administration.Twelve of 25 infants (48%) developed repolarization abnormalities with cisapride administration: 32% of the infants (8/25) studied had QTc prolongation (>/=0.450 seconds), whereas 10/25 had JTc prolongation (>/=0.360 seconds). Preterm infants <32 weeks significantly prolonged their QTc interval from 0.41 +/- 0.02 to 0.44 +/- 0.02. The QTc and/or JTc was prolonged in 54% of infants receiving 0.1 mg/kg/dose and 42% receiving 0.2 mg/kg/dose.The QTc and JTc interval significantly prolonged in preterm infants <32 weeks on the recommended dose of cisapride therapy. A QTc >/=0.450 seconds developed in 32% of infants treated with cisapride, whereas the JTc prolonged in 40%. A significant percentage of infants (54%) developed prolonged QTc intervals at a dose of 0.1 mg/kg/dose. From these data we conclude that there is a higher risk of prolongation of the QTc interval and risk of arrhythmias with greater prematurity.

View details for Web of Science ID 000169105500034

View details for PubMedID 11389249
Using 12-lead ECG and synthesized VCG in detection of right ventricular hypertrophy with terminal right conduction delay versus partial right bundle branch block in the pediatric population Zhou, S. H., Liebman, J., Dubin, A. M., Gillette, P. C., Gregg, R. E., Helfenbein, E. D., Lindauer, J. M. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2001: 249-257
Abstract

In pediatric electrocardiogram (ECG) analysis, mild right ventricular hypertrophy (RVH) and especially mild RVH with terminal right conduction delay (RVHtcd) are often confused with partial right bundle branch block (PRBBB). This is problematic for computer ECG analysis algorithms and even for most experienced pediatric cardiologists. This study was designed to achieve better classification of mild RVHtcd and PRBBB by combining the 12-lead synthesized vectocardiogram (VCG) transverse plane measurements with scalar ECG measurements. Pediatric ECGs used in the study were recorded with 15 leads and a 500 Hz sampling rate at the Lucile Salter Packard Children's Hospital, Stanford University Medical Center. Out of 4,200 ECGs collected consecutively over a period of 18 months, 447 RVH, 335 RBBB and 589 Normal were interpreted by expert pediatric cardiologists, and were included in the study. Statistical comparison of ECG and VCG measurements were done in stratified ECG sets (412) that have a visually indistinguishable waveform pattern, 117 RVHtcd, 96 PRBBB and 199 normal, showed significant differences in initial and terminal vectors in the transverse plane. The mean angle of the initial vector was anterior (57.2 degrees +/- 41.8) in the normal group, left anterior in the PRBBB group (34.4 degrees +/- 39.5) and in the RVHtcd group (31.9 degrees +/- 41.0) and. The mean angle of the terminal vector was right anterior (158.3 degrees +/- 36.8) in the PRBBB group, rightward (179.7 degrees +/- 29.9) in the RVHtcd group and right posterior (212.6 degrees +/- 37.8) in the normal group. These are clearly applicable features for a classification algorithm. Significantly improved classification results were obtained from a new algorithm using combined ECG and VCG measurements versus an existing algorithm. The limitation of this study stems from the unavailability of a more reliable gold standard. It may be necessary to used body surface potentials obtained with a large number of electrodes to accurately differentiate the study groups.

View details for Web of Science ID 000173072300038

View details for PubMedID 11781964
Radiofrequency catheter ablation: Indications and complications PEDIATRIC CARDIOLOGY Dubin, A. M., Van Hare, G. F. 2000; 21 (6): 551-556
Abstract

Radiofrequency catheter ablation was first described in pediatric patients in the early 1990s. Since then, multiple advances in the technology and understanding of radiofrequency ablation have allowed this technique to blossom into one of the most powerful therapeutic tools available to the pediatric electrophysiologist. This treatment has, in the majority of cases, replaced arrhythmia surgery as the definitive cure for most arrhythmias. Ablation therapy is commonly implemented as an elective procedure to treat paroxysmal reentrant supraventricular tachycardia. There are several advantages to this therapy when used in the common indications: no exercise restrictions, no need for chronic drug therapy, and the avoidance of hospital visits for breakthrough episodes. This review will discuss the indications for radiofrequency ablation in the current era. In order to fully discuss this issue, this review will include the prior treatment of arrhythmias, current success rates, complications, and potential long-term issues.

View details for Web of Science ID 000090052400007

View details for PubMedID 11050279
In vivo role of beta-adrenergic receptors in AV nodal conduction Dubin, A. M., Schauble, E. H., Powers, J., Kobilka, B. K., Bernstein, D. LIPPINCOTT WILLIAMS & WILKINS. 2000: 3-3
View details for Web of Science ID 000090072300003
Outcome while awaiting heart transplantation in children: A comparison of congenital heart disease and cardiomyopathy JOURNAL OF HEART AND LUNG TRANSPLANTATION Rosenthal, D. N., Dubin, A. M., Chin, C., Falco, D., Gamberg, P., Bernstein, D. 2000; 19 (8): 751-755
Abstract

Outcomes for children who undergo heart transplantation differ for children with congenital heart disease as compared to those with structurally normal hearts. Similar data have not been reported for these groups of patients for the morbidity and mortality associated with waiting for a donor. We report these data.A retrospective review was performed for all pediatric patients who were listed for heart transplantation at Stanford from 1977 to 1996, comparing mortality and major morbidity for patients with congenital heart disease and those with cardiomyopathy and structurally normal hearts.There were 96 patients who met study criteria, of whom 67 were successfully transplanted. The median waiting time was 23 days. Survival at 30 days was 93% and at 90 days was 81%, with no difference between groups. Major complications were identified in 38% of patients with structurally normal hearts, vs 9% of patients with congenital heart disease (p < 0.001).Overall mortality is similar for patients with congenital heart disease and those with structurally normal hearts while listed for heart transplantation, but patients with congenital heart disease have fewer episodes of major morbidity during this time.

View details for Web of Science ID 000089041400005

View details for PubMedID 10967268
Antiarrhythmic drug therapy in the neonate PROGRESS IN PEDIATRIC CARDIOLOGY Dubin, A. 2000; 11 (1): 55-63
Abstract

The neonate presents a challenge for the practitioner considering antiarrhythmic therapy: pharmacokinetics are different than in older children or adults; and the arrhythmia substrate may also differ, with respect to issues of ion channel and autonomic nervous system development. This paper reviews the need for antiarrhythmic drug therapy in the neonate, developmental aspects of pharmacokinetics, autonomic regulation and cellular electrophysiology and the antiarrhythmics available today with an emphasis on newer drug therapy.

View details for Web of Science ID 000087522400006
Influence of prone-supine position on sleep and heart rate variability in preterm infants at one month corrected age Adams, M., Mirmiran, M., Dubin, A., Boeddiker, M., Baldwin, R., Ariagno, R. NATURE PUBLISHING GROUP. 2000: 383A-383A
View details for Web of Science ID 000086155302260
Advances in the treatment of cardiac rhythm disturbances. Current opinion in pediatrics Dubin, A. M., Van Hare, G. F. 1999; 11 (5): 433-436
Abstract

Many advances in the care of children with cardiac rhythm disturbances have been made in the past year. From the fetus with supraventricular tachycardia to the adolescent with vasovagal syncope, new and effective therapies have evolved. Molecular genetics has led to monumental leaps in the understanding of long QT syndrome, and a new pharmacologic alternative to cardioversion has been introduced. There have also been new and noteworthy developments in the more established area of radiofrequency ablation. These concern safety and also touch on one of today's most controversial areas, cost effectiveness. This article discusses each of these advances in the realm of pediatric cardiac electrophysiology.

View details for PubMedID 10555596
QT dispersion predicts ventricular arrhythmia in pediatric cardiomyopathy patients referred for heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Dubin, A. M., Rosenthal, D. N., Chin, C., Bernstein, D. 1999; 18 (8): 781-785
Abstract

QT dispersion has been used in stratifying risk for sudden death in adults with dilated cardiomyopathy, but its role in the pediatric population has not been delineated.We reviewed electrocardiograms in pediatric patients with dilated cardiomyopathy referred for heart transplantation, to evaluate the role of QT dispersion in predicting malignant arrhythmias in these patients. Three groups were defined: Group I (n = 13) had dilated cardiomyopathy and malignant ventricular arrhythmias, Group II (n = 13) had dilated cardiomyopathy with no ventricular arrhythmias and Group III (n = 30) consisted of normals. QT dispersion was defined as the duration of the shortest QT subtracted from that of the longest. In addition, the standard deviation of the QT intervals was calculated for each ECG, using 12 leads.QT dispersion was significantly prolonged in Group I (97 +/- 33 msec) compared to Group II (74 +/- 19 msec) and Group III (42 +/- 17 msec). QT standard deviation was also prolonged in Group I (30 +/- 11 msec) vs Group II (22 +/- 5 msec) and Group III (13 +/- 4 msec). Using a threshold value of 90 msec for QT dispersion or 25 msec for QT standard deviation, a sensitivity of 78% and a specificity of 70% was obtained for identifying patients who would subsequently develop ventricular arrhythmias.In pediatric heart transplant candidates with dilated cardiomyopathy, QT dispersion and QT standard deviation identify patients at higher risk for the development of malignant ventricular arrhythmia. This simple test can be helpful in the evaluation and management of these patients awaiting transplantation.

View details for Web of Science ID 000082347500007

View details for PubMedID 10512525
Effect of mental stress on heart rate variability: Validation of simulated operating and delivery room training modules Kaegi, D. M., Halamek, L. P., Van Hare, G. F., Howard, S. K., Dubin, A. M. NATURE PUBLISHING GROUP. 1999: 77A-77A
View details for Web of Science ID 000079476700447
A new therapeutic approach to the fetus with congenital complete heart block: Preemptive, targeted therapy with dexamethasone OBSTETRICS AND GYNECOLOGY Rosenthal, D., Druzin, M., Chin, C., Dubin, A. 1998; 92 (4): 689-691
Abstract

Therapy of established congenital complete heart block in the fetus has resulted in improved survival but persistence of heart block. This exposes the infant to the morbidity of heart block, including the risk of sudden death and pacemaker implantation.A 35-year-old gravida 2, para 1, with Sjogren syndrome and a previous pregnancy complicated by congenital complete heart block presented during her second pregnancy. Intensive fetal monitoring with echocardiography was employed. Early evidence of myocardial dysfunction and dysrhythmia was found, dexamethasone therapy was initiated, and the dysfunction and dysrhythmia resolved. The pregnancy went to term without further complication.This represents a new and successful strategy to identify very early signs of myocardial disease in a fetus at high risk of congenital complete heart block, enabling targeted, preemptive therapy.

View details for Web of Science ID 000076159900022

View details for PubMedID 9764666
Heart rate variability as a marker for workload during neonatal resuscitation Kaegi, D. M., Halamek, L. P., Dubin, A., Howard, S. AMER ACAD PEDIATRICS. 1998: 766-767
View details for Web of Science ID 000075810500223
Arrhythmias and thromboembolic complications after the extracardiac Fontan operation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shirai, L. K., Rosenthal, D. N., Reitz, B. A., Robbins, R. C., Dubin, A. M. 1998; 115 (3): 499-505
Abstract

Late morbidity and mortality after the Fontan operation are largely due to atrial arrhythmias, ventricular failure, and thrombus formation. The extracardiac Fontan procedure avoids extensive atrial manipulation and suture lines, theoretically minimizing the impetus for these events. We examined our experience with the extracardiac Fontan operation with particular attention to thromboembolism and arrhythmias.We retrospectively reviewed the medical and surgical records of all 16 patients who underwent an extracardiac Fontan operation between July 1993 and May 1996. Fifteen patients (94%) were in sinus rhythm before the operation. In the immediate postoperative period, seven (44%) had arrhythmias consisting of accelerated junctional rhythm and ectopic atrial rhythm. No associated hemodynamic compromise and no early deaths occurred. Patients were followed up for 3 to 34 months after the Fontan operation. Arrhythmias were detected in eight patients (50%) on surface electrocardiograms, and seven (44%) showed evidence of sinus node dysfunction on 24-hour Holter monitor studies. Thrombi were found in three patients (19%). All patients were asymptomatic, with no evidence of conduit obstruction by echocardiogram.The incidence of hemodynamically significant tachyarrhythmias appears to be reduced after the extracardiac Fontan operation. A significant percentage of patients have evidence of sinus node dysfunction, suggesting the presence of other surgical or nonsurgical factors responsible for this finding. Our incidence of thrombotic events is similar to previous reports with other Fontan modifications. It appears to be a reasonable option to maintain these patients on anticoagulation indefinitely.

View details for Web of Science ID 000072718800002

View details for PubMedID 9535435
Radiofrequency catheter ablation for paroxysmal supraventricular tachycardia in children and adolescents without structural heart disease AMERICAN JOURNAL OF CARDIOLOGY Kugler, J. D., Danford, D. A., Houston, K., Felix, G., Erickson, C., Schenck, M., Campbell, R., Hulse, E., Walsh, E., Saul, P., Ross, B., Karpawich, P., Epstein, M., Vetter, V., Rhodes, L., Beerman, L., Perry, J., Cecchin, F., Deal, B., Benson, J. W., Sterba, R., Hordoff, A., Gillette, P., Case, C., Dick, M., WEINDLING, S., Schaffer, M. S., Kanter, R., Berul, C., Cohen, M., Kuehl, K., Beder, S., Hubbard, J., McCormack, J., KURER, C., Porter, C., Wolff, G., Young, M. L., Burton, D., FISHBERGER, S., Silka, M., Judd, V., Etheridge, S., VanHare, G. F., Bromberg, B., Dubin, A., Byrum, C., Friedman, R., FENRICH, A., HAMILTON, R., Gow, R., Park, J., Klitzner, T., Lau, Y., VANHARE, G., Atkins, D., Kugler, J., Scott, W., Fish, F. 1997; 80 (11): 1438-1443
View details for Web of Science ID A1997YJ52400009
USE OF THE RATE-CORRECTED JT INTERVAL FOR PREDICTION OF REPOLARIZATION ABNORMALITIES IN CHILDREN AMERICAN JOURNAL OF CARDIOLOGY Berul, C. I., Sweeten, T. L., Dubin, A. M., Shah, M. J., Vetter, V. L. 1994; 74 (12): 1254-1257
Abstract

A prolonged rate-corrected QT interval (QTc) may be associated with an increased risk of developing ventricular arrhythmias and sudden death, particularly in patients with the hereditary long QT syndrome (LQTS), myocardial ischemia, or antiarrhythmic medication toxicity. It is known that there are some patients with LQTS who sometimes have a borderline or normal QTc (< or = 0.45 second). Although the QTc has been the standard measurement of ventricular repolarization, it includes both depolarization and repolarization and may not always be a sensitive indicator of the type of repolarization abnormalities seen in LQTS. Intraventricular conduction abnormalities complicate evaluation of the QTc interval. The rate-corrected JT interval (JTc) is a more accurate measurement of ventricular repolarization, and therefore may be a more sensitive means of assessing abnormalities. The QTc on a resting electrocardiogram was determined in 40 patients with LQTS and in 31 patients with right bundle branch block after tetralogy of Fallot repair. These were compared with 1,000 age-matched control subjects. The right bundle branch block group had normal JT and JTc measurements, despite having prolonged QT and QTc intervals compared with controls. The JTc identified 85% of patients affected with LQTS compared with only 58% identified using only the QTc as a marker for the syndrome. The JTc is a more specific measurement of ventricular repolarization than the QTc by eliminating QRS duration variability. It appears to be a more sensitive predictor of repolarization abnormalities, and may be helpful in identifying patients with LQTS who have borderline or normal QTc measurements on resting electrocardiograms.

View details for Web of Science ID A1994PV91000015

View details for PubMedID 7977100

Professor of Pediatrics (Pediatric Cardiology) at the Lucile Salter Packard Children's Hospital

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