Anne Dubin

All Publications

• QTc Prolongation and Risk of Torsades de Pointes in Hospitalized Pediatric Oncology Patients. The Journal of pediatrics Lim, T. R., Rangaswami, A. A., Dubin, A. M., Kapphahn, K. I., Sakarovitch, C., Long, J., Motonaga, K. S., Trela, T., Ceresnak, S. R. 2019

  Abstract

  OBJECTIVE: To evaluate the prevalence of torsades de pointes and to identify risk factors associated with QTc prolongation of ≥500milliseconds in hospitalized pediatric oncology patients. A QTc prolongation of ≥500milliseconds is associated with higher mortality in hospitalized adults but has not been demonstrated in pediatrics.STUDY DESIGN: A single-center, retrospective review of all hospitalized oncology patients ≤21years of age was performed from 2014 to 2016. Patients with long/short QT syndrome or a QRS interval of ≥120ms were excluded. Rapid response events were reviewed to determine the prevalence of torsades. In patients with ECGs for review, data were compared between patients with a QTc of <500 and≥500ms via logistic regression.RESULTS: There were 1934 hospitalized patients included. Rapid response events occurred in 90 patients (4.7%) with 2 torsades events (0.1%). There were 1412 electrocardiograms performed in 287 unique patients (10.6±6.3years of age; 43% female). The mean QTc was 448±31ms; 25 patients (8.7%) had ≥1 ECG with a QTc of ≥500ms. The prevalence of torsades was greater in patients with a QTc of ≥500ms (8% vs 0%; P<.01). In multivariate analysis, factors associated with a QTc of ≥500ms included female sex, (OR 2.95) and ≥2 QT-prolonging medications (OR, 2.95).CONCLUSIONS: The prevalence of torsades in hospitalized pediatric oncology patients was low (0.1%), although the risk was significantly greater in patients with a QTc of ≥500ms. Routine monitoring of electrocardiograms and electrolytes is essential in patients with risk factors predisposing to QTc prolongation.

  View details for DOI 10.1016/j.jpeds.2019.10.018

  View details for PubMedID 31761428

• Broad Genetic Testing in a Clinical Setting Uncovers a High Prevalence of Titin Loss-of-Function Variants in Very Early-Onset Atrial Fibrillation. Circulation. Genomic and precision medicine Goodyer, W. R., Dunn, K., Caleshu, C., Jackson, M., Wylie, J., Moscarello, T., Platt, J., Reuter, C., Smith, A., Trela, A., Ceresnak, S. R., Motonaga, K. S., Ashley, E., Yang, P., Dubin, A. M., Perez, M. 2019

  Abstract

  Atrial fibrillation (AF) is the most common sustained arrhythmia, affecting approximately 34 million worldwide. The pathophysiology of AF remains incompletely understood but is clearly complex with multiple underlying genetic, physiologic and environmental factors. Very early-onset AF (vEAF) (defined here as onset <45 years and without significant comorbidities), while rare (only ~0.5-3% of AF cases), is highly heritable, with a greater prevalence of rare variants in genes previously associated with AF. Patients with vEAF, therefore, represent an ideal population for discovering novel genes involved in the underlying genetic basis of AF. Notably, the Framingham study showed that patients with AF without comorbidities have a three-fold higher risk for heart failure. Conversely, several forms of inherited cardiomyopathy have been strongly associated with AF suggestive of a shared etiology.

  View details for DOI 10.1161/CIRCGEN.119.002713

  View details for PubMedID 31638414

• Management of Asymptomatic Wolff-Parkinson-White Pattern by Pediatric Electrophysiologists. The Journal of pediatrics Chubb, H., Campbell, R. M., Motonaga, K. S., Ceresnak, S. R., Dubin, A. M. 2019

  Abstract

  OBJECTIVE: To determine the present-day approach of pediatric cardiac electrophysiologists to asymptomatic Wolff-Parkinson-White (WPW) pattern and to contrast to both published consensus statements and a similar survey.STUDY DESIGN: A questionnaire was sent to 266 Pediatric and Congenital Electrophysiology Society physician members in 25 countries; 21 questions from the 2003 survey were repeated, with new questions added regarding risk stratification and decision making.RESULTS: We received 113 responses from 13 countries, with responders having extensive electrophysiology experience (median 15years [IQR 8.5-25years]). Only 12 (11%) believed that intermittent pre-excitation and 37 (33%) that sudden loss of pre-excitation on exercise test were sufficient evidence of accessory pathway safety to avoid an invasive electrophysiology study. Optimal weight for electrophysiology study was 20kg (IQR 18-22.5kg), and 61% and 58% would then ablate all right-sided or left-sided accessory pathways, respectively, regardless of electrophysiological properties, whereas only 23% would ablate all septal accessory pathways (P<.001). Compared with 2003, respondents were more likely to consider inducible arrhythmia (77% vs 26%, P<.001) as sufficient indication alone for ablation.CONCLUSIONS: In the context of recent literature regarding the reliability of risk-stratification tools, most operators are now performing electrophysiology study for asymptomatic Wolff-Parkinson-White regardless of noninvasive findings. Many will then proceed to default ablation of all accessory pathways distant from critical conduction structures.

  View details for DOI 10.1016/j.jpeds.2019.05.058

  View details for PubMedID 31235382

• A novel pacing maneuver to verify the postpacing interval minus the tachycardia cycle length while adjusting for decremental conduction: Using "dual-chamber entrainment" for improved supraventricular tachycardia discrimination HEART RHYTHM Kaiser, D. W., Nasir, J. M., Liem, L., Brodt, C., Motonaga, K. S., Ceresnak, S. R., Turakhia, M. P., Dubin, A. M. 2019; 16 (5): 717–23

  View details for DOI 10.1016/j.hrthm.2018.11.021

  View details for Web of Science ID 000466096200013

• Extended cardiac ambulatory rhythm monitoring in adults with congenital heart disease: Arrhythmia detection and impact of extended monitoring CONGENITAL HEART DISEASE Schultz, K. E., Lui, G. K., McElhinney, D. B., Long, J., Balasubramanian, V., Sakarovitch, C., Fernandes, S. M., Dubin, A. M., Rogers, I. S., Romfh, A. W., Motonaga, K. S., Viswanathan, M. N., Ceresnak, S. R. 2019; 14 (3): 410–18

  View details for DOI 10.1111/chd.12736

  View details for Web of Science ID 000471070900013

• Pediatric and congenital electrophysiology society initiative on device needs in pediatric electrophysiology HEART RHYTHM Dubin, A. M., Cannon, B. C., Saarel, E. V., Triedman, J. K., Berul, C. I., Bar-Cohen, Y., Shah, M. J., Paulsen, J., Patel, H., Reich, J., Carlson, M. D., Stein, K., Gilkerson, J. O., Kowal, R. C., Peiris, V. 2019; 16 (4): E39-+

  View details for DOI 10.1016/j.hrthm.2018.12.021

  View details for Web of Science ID 000462618400003

• Comparison of the Medtronic SelectSecure and conventional pacing leads: Long-term follow-up in a multicenter pediatric and congenital cohort PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Moak, J. P., Law, I. H., LaPage, M. J., Fish, F., Shatty, I., Dubin, A. M., Patel, A., Fishbach, P., Cain, N., Johnsrude, C., Berul, C. I., Bangoura, A., Hanumanthaiah, S., McCarter, R. 2019; 42 (3): 356–65

  View details for DOI 10.1111/pace.13614

  View details for Web of Science ID 000460951100011

• Comparison of the medtronic selectsecure and conventional pacing leads: long term follow-up in a multicenter pediatric and congenital cohort. Pacing and clinical electrophysiology : PACE Moak, J. P., Law, I. H., LaPage, M. J., Fish, F., Shatty, I., Dubin, A. M., Patel, A., Fishbach, P., Cain, N., Johnsrude, C., Berul, C. I., Bangoura, A., Hanumanthaiah, S., McCarter, R. 2019

  Abstract

  INTRODUCTION: The Medtronic SelectSecure pacing lead (SS) has theoretical advantages compared to conventional (C) transvenous pacing leads (PL). The study purpose was to determine whether differences in electrical function and lead survival exist between these PL in a large data set of pediatric and congenital patients.METHODS: A multicenter historical longitudinal cohort study was performed comparing SS and CPL performance over a 72-month follow-up (FU). Ten centers provided data for both SS and CPL, matched for age, implanted pacing chamber, time period of implantation, and presence of heart disease.RESULTS: The cohort consisted of 141 subjects in each group. No statistical differences were observed in age, gender, presence of heart disease, or pacing indication. Atrial and ventricular capture thresholds were stable throughout FU and higher in the SS group (atrial: 0.75 ± 0.02 vs. 0.5 ± 0.04 V, ventricular: 1.0 ± 0.04 vs. 0.75 ± 0.04 V), p<0.001. Group PL sensing thresholds did not differ. The SS group required greater energy to pace (atrial: 0.57 ± 0.05 vs. 0.32 ± 0.02 mJ, ventricular: 0.83 ± 0.05 vs. 0.56 ± 0.06 mJ), p=0.001. Early lead dislodgement and phrenic nerve stimulation were greater in the SS group (p=0.03). Long-term lead survival was high and similar between the two groups, p=0.35.CONCLUSIONS: Long-term survival of both PL was high with a low fracture rate. The SS had excellent electrical function but did show higher capture thresholds and increased energy to pace; these differences are offset by other advantages of the SS PL. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30680764

• Extended cardiac ambulatory rhythm monitoring in adults with congenital heart disease: Arrhythmia detection and impact of extended monitoring. Congenital heart disease Schultz, K. E., Lui, G. K., McElhinney, D. B., Long, J., Balasubramanian, V., Sakarovitch, C., Fernandes, S. M., Dubin, A. M., Rogers, I. S., Romfh, A. W., Motonaga, K. S., Viswanathan, M. N., Ceresnak, S. R. 2019

  Abstract

  BACKGROUND: Arrhythmias are a leading cause of death in adults with congenital heart disease (ACHD). While 24-48-hour monitors are often used to assess arrhythmia burden, extended continuous ambulatory rhythm monitors (ECAM) can record 2 weeks of data. The utility of this device and the arrhythmia burden identified beyond 48-hour monitoring have not been evaluated in the ACHD population. Additionally, the impact of ECAM has not been studied to determine management recommendations.OBJECTIVE: To address the preliminary question, we hypothesized that clinically significant arrhythmias would be detected on ECAM beyond 48hours and this would lead to clinical management changes.METHODS: A single center retrospective cohort study of ACHD patients undergoing ECAM from June 2013 to May 2016 was performed. The number and type of arrhythmias detected within and beyond the first 48hours of monitoring were compared using Kaplan-Meier curves and Cox proportional hazard models.RESULTS: Three hundred fourteen patients had monitors performed [median age 31 (IQR 25-41) years, 61% female). Significant arrhythmias were identified in 156 patients (50%), of which 46% were noted within 48 hours. A management change based on an arrhythmia was made in 49 patients (16%).CONCLUSIONS: ECAM detects more clinically significant arrhythmias than standard 48-hour monitoring in ACHD patients. Management changes, including medication changes, further testing or imaging, and procedures, were made based on results of ECAM. Recommendations and guidelines have been made based on arrhythmias on 48-hour monitoring; the predictive ability and clinical consequence of arrhythmias found on ECAM are not yet known.

  View details for PubMedID 30604934

• Validation of a novel automated signal analysis tool for ablation of Wolff-Parkinson-White Syndrome. PloS one Ceresnak, S. R., Pass, R. H., Dubin, A. M., Yang, L., Motonaga, K. S., Hedlin, H., Avasarala, K., Trela, A., McElhinney, D. B., Janson, C., Nappo, L., Ling, X. B., Gates, G. J. 2019; 14 (6): e0217282

  Abstract

  BACKGROUND: In previous pilot work we demonstrated that a novel automated signal analysis tool could accurately identify successful ablation sites during Wolff-Parkinson-White (WPW) ablation at a single center.OBJECTIVE: We sought to validate and refine this signal analysis tool in a larger multi-center cohort of children with WPW.METHODS: A retrospective review was performed of signal data from children with WPW who underwent ablation at two pediatric arrhythmia centers from 2008-2015. All patients with WPW ≤ 21 years who underwent invasive electrophysiology study and ablation with ablation signals available for review were included. Signals were excluded if temperature or power delivery was inadequate or lesion time was < 5 seconds. Ablation lesions were reviewed for each patient. Signals were classified as successful if there was loss of antegrade and retrograde accessory pathway (AP) conduction or unsuccessful if ablation did not eliminate AP conduction. Custom signal analysis software analyzed intracardiac electrograms for amplitudes, high and low frequency components, integrated area, and signal timing components to create a signal score. We validated the previously published signal score threshold 3.1 in this larger, more diverse cohort and explored additional scoring options. Logistic regression with lasso regularization using Youden's index criterion and a cost-benefit criterion to identify thresholds was considered as a refinement to this score.RESULTS: 347 signals (141 successful, 206 unsuccessful) in 144 pts were analyzed [mean age 13.2 ± 3.9 years, 96 (67%) male, 66 (45%) left sided APs]. The software correctly identified the signals as successful or unsuccessful in 276/347 (80%) at a threshold of 3.1. The performance of other thresholds did not significantly improve the predictive ability. A signal score threshold of 3.1 provided the following diagnostic accuracy for distinguishing a successful from unsuccessful signal: sensitivity 83%, specificity 77%, PPV 71%, NPV 87%.CONCLUSIONS: An automated signal analysis software tool reliably distinguished successful versus unsuccessful ablation electrograms in children with WPW when validated in a large, diverse cohort. Refining the tools using an alternative threshold and statistical method did not improve the original signal score at a threshold of 3.1. This software was effective across two centers and multiple operators and may be an effective tool for ablation of WPW.

  View details for DOI 10.1371/journal.pone.0217282

  View details for PubMedID 31242221

• A Prospective Assessment of Optimal Mechanical Ventilation Parameters for Pediatric Catheter Ablation PEDIATRIC CARDIOLOGY Janson, C. M., Ceresnak, S. R., Choi, J. M., Dubin, A. M., Motonaga, K. S., Mann, G. E., Kahana, M., Fitz-James, I., Wise-Faberowski, L., Kamra, K., Nappo, L., Trela, A., Pass, R. H. 2019; 40 (1): 126–32

  Abstract

  Catheter stability, an important factor in ablation success, is affected by ventilation. Optimal ventilation strategies for pediatric catheter ablation are not known. We hypothesized that small tidal volume and positive end-expiratory pressure are associated with reduced ablation catheter movement at annular positions. Subjects aged 5-25 years undergoing ablation for supraventricular tachycardia (SVT) or WPW at two centers from March 2015 to September 2016 were prospectively enrolled and randomized to receive mechanical ventilation with either positive end-expiratory pressure of 5 cm H2O (PEEP) or 0 cm H2O (ZEEP). Movement of the ablation catheter tip at standard annular positions was measured using 3D electroanatomic mapping systems under two conditions: small tidal volume (STV) (3-5 mL/kg) or large TV (LTV) (6-8 mL/kg). 58 subjects (mean age 13.8 years) were enrolled for a total of 266 separate observations of catheter movement. STV ventilation was associated with significantly reduced catheter movement, compared to LTV at all positions (right posteroseptal: 2.5 ± 1.4 vs. 5.2 ± 3.1 mm, p < 0.0001; right lateral: 2.7 ± 1.6 vs. 6.3 ± 3.5 mm, p < 0.0001; left lateral: 1.8 ± 1.0 vs. 4.3 ± 1.9 mm, p < 0.0001). The presence or absence of PEEP had no effect on catheter movement. In multivariable analysis, STV was associated with a 3.1-mm reduction in movement (95% CI 2.6-3.5, p < 0.0001), adjusting for end-expiratory pressure, annular location, and patient size. We conclude that STV ventilation is associated with reduced ablation catheter movement compared to a LTV strategy, independent of PEEP and annular position.

  View details for PubMedID 30178187

• What have we learned in the last 20 years? A comparison of a modern era pediatric and congenital catheter ablation registry to previous pediatric ablation registries HEART RHYTHM Dubin, A. M., Jorgensen, N. W., Radbill, A. E., Bradley, D. J., Silva, J. N., Tsao, S., Kanter, R. J., Tanel, R. E., Trivedi, B., Young, M., Pflaumer, A., McCormack, J., Seslar, S. P. 2019; 16 (1): 57–63

  View details for DOI 10.1016/j.hrthm.2018.08.013

  View details for Web of Science ID 000454718800016

• A proposed method for the calculation of age-dependent QRS duration z-scores. Journal of electrocardiology Chubb, H., Ceresnak, S. R., Motonaga, K. S., Dubin, A. M. 2019; 58: 132–34

  Abstract

  There are currently no published algorithms for calculation of age-dependent QRS duration z-scores. The absence of a standardized measure has limited researchers' abilities to compare ECG measurements of electrical synchrony between subjects of different ages or longitudinally over time.Four existing studies of normal ECG measurements (total 19,062 subjects) were used to estimate age and sex-dependent means and standard deviations.Weighted means and standard deviations were best estimated by cubic functions to create z-score algorithms.Nomograms and algorithms for QRS duration z-scores may be estimated to compare ECG findings in both children and adults.

  View details for DOI 10.1016/j.jelectrocard.2019.12.004

  View details for PubMedID 31846856

• Pediatric and Congenital Electrophysiology Society Initiative on Device Needs in Pediatric Electrophysiology. Heart rhythm Dubin, A. M., Cannon, B. C., Saarel, E. V., Triedman, J. K., Berul, C. I., Bar-Cohen, Y., Shah, M. J., Paulsen, J., Patel, H., Reich, J., Carlson, M. D., Stein, K., Gilkerson, J. O., Kowal, R. C., Peiris, V. 2018

  View details for PubMedID 30579977

• A Novel Pacing Maneuver to Verify the Post-Pacing Interval Minus the Tachycardia Cycle Length While Adjusting for Decremental Conduction: Using 'Dual Chamber Entrainment' for Improved Supraventricular Tachycardia Discrimination. Heart rhythm Kaiser, D. W., Nasir, J. M., Liem, L. B., Brodt, C., Motonaga, K. S., Ceresnak, S. R., Turakhia, M. P., Dubin, A. M. 2018

  Abstract

  BACKGROUND: The post-pacing interval (PPI) minus the tachycardia cycle length (TCL) is frequently used to investigate tachycardias. However, a variety of issues (e.g. failure to entrain, decremental conduction, and oscillating TCLs) can make interpretation of the PPI-TCL challenging.OBJECTIVES: To investigate a novel maneuver to confirm the PPI-TCL value without using either the ventricular PPI or the TCL interval. To assess the ability of this maneuver to identify decremental conduction and differentiate supraventricular tachycardias.METHODS: We analyzed 77 intracardiac recordings from patients [age 25±20 years, 40 female] who underwent catheter ablation of AVNRT or orthodromic reciprocating tachycardia (ORT) with a concealed pathway. We calculated the PPI-TCL, the AH-corrected PPI-TCL, and estimated the PPI-TCL using "dual chamber entrainment" calculated as: [PPIV-TCL=Stim(AoV)+Stim(VoA)-PPIA].RESULTS: The PPI-TCL calculated by dual chamber entrainment highly correlated with the observed and AH-corrected PPI-TCL [R2=0.79 and 0.96, respectively, p<0.001]. A dual chamber entrainment PPI-TCL value of 80ms correctly differentiated all AVNRT from septal ORT cases, whereas the standard PPI-TCL and AH-corrected PPI-TCL methods were incorrect in 14% and 6% of cases, respectively. Dual chamber entrainment identified 3±10ms of additional decremental conduction beyond AH-prolongation, including four pathways with significant (>10ms) decrement.CONCLUSION: Dual chamber entrainment estimates the PPI-TCL value without using either the ventricular PPI or the TCL interval. This maneuver adjusts for all decremental conduction, including within concealed pathways, where a dual chamber entrainment PPI-TCL value >80ms favors AVNRT over ORT. This maneuver can be used to verify the observed PPI-TCL value in challenging cases.

  View details for PubMedID 30465902

• SCN5A mutations in 442 neonates and children: genotype-phenotype correlation and identification of higher-risk subgroups EUROPEAN HEART JOURNAL Baruteau, A., Kyndt, F., Behr, E. R., Vink, A. S., Lachaud, M., Joong, A., Schott, J., Horie, M., Denjoy, I., Crotti, L., Shimizu, W., Bos, J. M., Stephenson, E. A., LeonieWong, Abrams, D. J., Davis, A. M., Winbo, A., Dubin, A. M., Sanatani, S., Liberman, L., Kaski, J., Rudic, B., Kwok, S., Rieubland, C., Tfelt-Hansen, J., Van Hare, G. F., Guyomarc'h-Delasalle, B., Blom, N. A., Wijeyeratne, Y. D., Gourraud, J., Le Marec, H., Ozawa, J., Fressart, V., Lupoglazoff, J., Dagradi, F., Spazzolini, C., Aiba, T., Tester, D. J., Zahavich, L. A., Beausejour-Ladouceur, V., Jadhav, M., Skinner, J. R., Franciosi, S., Krahn, A. D., Abdelsayed, M., Ruben, P. C., Yung, T., Ackerman, M. J., Wilde, A. A., Schwartz, P. J., Probst, V. 2018; 39 (31): 2879-+

  Abstract

  To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification.A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation were included in the analysis. There was no restriction made based on their clinical diagnosis. A total of 442 children {55.7% boys, 40.3% probands, median age: 8.0 [interquartile range (IQR) 9.5] years} from 350 families were included; 67.9% were asymptomatic at diagnosis. Four main phenotypes were identified: isolated progressive cardiac conduction disorders (25.6%), overlap phenotype (15.6%), isolated long QT syndrome type 3 (10.6%), and isolated Brugada syndrome type 1 (1.8%); 44.3% had a negative electrocardiogram phenotype. During a median follow-up of 5.9 (IQR 5.9) years, 272 cardiac events (CEs) occurred in 139 (31.5%) patients. Patients whose mutation localized in the C-terminus had a lower risk. Compound genotype, both gain- and loss-of-function SCN5A mutation, age ≤1 year at diagnosis in probands and age ≤1 year at diagnosis in non-probands were independent predictors of CE.In this large paediatric cohort of SCN5A mutation-positive subjects, cardiac conduction disorders were the most prevalent phenotype; CEs occurred in about one-third of genotype-positive children, and several independent risk factors were identified, including age ≤1 year at diagnosis, compound mutation, and mutation with both gain- and loss-of-function.

  View details for PubMedID 30059973

• What have we learned in the last 20 years? A Comparison of a Modern Era Pediatric and Congenital Catheter Ablation Registry to Prior Pediatric Ablation Registries. Heart rhythm Dubin, A. M., Jorgensen, N. W., Radbill, A. E., Bradley, D. J., Silva, J. N., Tsao, S., Kanter, R. J., Tanel, R. E., Trivedi, B., Young, M., Pflaumer, A., McCormack, J., Seslar, S. P. 2018

  Abstract

  BACKGROUND: Since the onset of pediatric catheter ablation, the pediatric electrophysiology community has reported outcomes via various registries (PAPCA and the Pediatric Catheter Ablation registry (PCAR)). Most recently, a modern era pediatric and congenital ablation registry (MAP-IT) was developed for eventual incorporation into the NCDR IMPACT registry.OBJECTIVE: We aimed to describe initial findings from the MAP-IT pilot registry, and compare these findings to earlier registries.METHODS: Prior to entering the NCDR IMPACT registry, MAP-IT was active at 12 centers (11 US) between October 2014 and April 2016. All EP studies were included for patients <21 years old and for patients of all ages with structural congenital heart disease (CHD). We compared the acute success, fluoroscopy and procedure times, and the frequency of complications between MAP-IT and the earlier registries.RESULTS: Acute success rates have improved from the initial PCAR registry for both accessory and slow pathway substrates. Both fluoroscopy and procedural time have significantly decreased across the time periods (fluoroscopy 47.6 ± 40 minutes down to 7.0 ± 9.2 minutes, p < 0.001; procedural time 257 ± 157 minutes to 166 ± 84 minutes, p <0.001).CONCLUSION: Acute success rates, fluoroscopy times and procedural times have all improved over the last 25 years in pediatric ablation.

  View details for PubMedID 30118886

• Utility of serial 12-lead electrocardiograms in children with Marfan syndrome CARDIOLOGY IN THE YOUNG Arunamata, A. A., Nguyen, C. T., Ceresnak, S. R., Dubin, A. M., Olson, I. L., Murphy, D. J., Tierney, E. 2018; 28 (8): 1009–13

  View details for DOI 10.1017/S1047951118000707

  View details for Web of Science ID 000439937200005

• Antibiotic Prophylaxis Practices in Pediatric Cardiac Implantable Electronic Device Procedures: A Survey of the Pediatric And Congenital Electrophysiology Society (PACES) PEDIATRIC CARDIOLOGY Chen, S. Y., Ceresnak, S. R., Motonaga, K. S., Trela, A., Hanisch, D., Dubin, A. M. 2018; 39 (6): 1129–33

  View details for DOI 10.1007/s00246-018-1865-0

  View details for Web of Science ID 000441721000009

• Utility of serial 12-lead electrocardiograms in children with Marfan syndrome. Cardiology in the young Arunamata, A. A., Nguyen, C. T., Ceresnak, S. R., Dubin, A. M., Olson, I. L., Murphy, D. J., Selamet Tierney, E. S. 2018: 1–5

  Abstract

  OBJECTIVES: The goal of this study was to assess the utility of serial electrocardiograms in routine follow-up of paediatric Marfan patients.METHODS: Children ⩽18 years who met the revised Ghent criteria for Marfan syndrome and received a 12-lead electrocardiogram and echocardiogram within a 3-month period were included. Controls were matched by age, body surface area, gender, race, and ethnicity, and consisted of patients assessed in clinic with a normal cardiac evaluation. Demographic, clinical, echocardiographic, and electrocardiographic data were collected.RESULTS: A total of 45 Marfan patients (10.8 [2.4-17.1] years) and 37 controls (12.8 [1.3-17.1] years) were included. Left atrial enlargement and left ventricular hypertrophy were more frequently present on 12-lead electrocardiogram of Marfan patients compared with controls (12 (27%) versus 0 (0%), p<0.001; and 8 (18%) versus 0 (0%), p=0.008, respectively); however, only two patients with left atrial enlargement on 12-lead electrocardiogram were confirmed to have left atrial enlargement by echocardiogram, and one patient had mild left ventricular hypertrophy by echocardiogram, not appreciated on 12-lead electrocardiogram. QTc interval was longer in Marfan patients compared with controls (427±16 versus 417±22 ms, p=0.03), with four Marfan patients demonstrating borderline prolonged QTc intervals for gender.CONCLUSIONS: While Marfan patients exhibited a higher frequency of left atrial enlargement and left ventricular hypertrophy on 12-lead electrocardiograms compared with controls, these findings were not supported by echocardiography. Serial 12-lead electrocardiograms in routine follow-up of asymptomatic paediatric Marfan patients may be more appropriate for a subgroup of Marfan patients only, specifically those with prolonged QTc interval at their baseline visit.

  View details for PubMedID 29972109

• Life-Threatening Event Risk in Children With Wolff-Parkinson-White Syndrome: A Multicenter International Study. JACC. Clinical electrophysiology Etheridge, S. P., Escudero, C. A., Blaufox, A. D., Law, I. H., Dechert-Crooks, B. E., Stephenson, E. A., Dubin, A. M., Ceresnak, S. R., Motonaga, K. S., Skinner, J. R., Marcondes, L. D., Perry, J. C., Collins, K. K., Seslar, S. P., Cabrera, M., Uzun, O., Cannon, B. C., Aziz, P. F., Kubus, P., Tanel, R. E., Valdes, S. O., Sami, S., Kertesz, N. J., Maldonado, J., Erickson, C., Moore, J. P., Asakai, H., Mill, L., Abcede, M., Spector, Z. Z., Menon, S., Shwayder, M., Bradley, D. J., Cohen, M. I., Sanatani, S. 2018; 4 (4): 433–44

  Abstract

  OBJECTIVES: This study sought to characterize risk in children with Wolff-Parkinson-White (WPW) syndrome by comparing those who had experienced a life-threatening event (LTE) with a control population.BACKGROUND: Children with WPW syndrome are at risk of sudden death.METHODS: This retrospective multicenter pediatric study identified 912 subjects≤21 years of age with WPW syndrome, using electrophysiology (EPS) studies. Case subjects had a history of LTE: sudden death, aborted sudden death, or atrialfibrillation (shortest pre-excited RR interval in atrial fibrillation [SPERRI] of≤250 ms or with hemodynamic compromise); whereas subjects did not. We compared clinical and EPS data between cases and subjects.RESULTS: Case subjects (n= 96) were older and less likely than subjects (n= 816) to have symptoms or documented tachycardia. Mean age at LTE was 14.1 ± 3.9 years of age. The LTE was the sentinel symptom in 65%, consisting of rapidly conducted pre-excited atrial fibrillation (49%), aborted sudden death (45%), and sudden death (6%). Three risk components were considered at EPS: SPERRI, accessory pathway effective refractory period (APERP), and shortest paced cycle length with pre-excitation during atrial pacing (SPPCL), and all were shorter in cases than in control subjects. In multivariate analysis, risk factors for LTE included male sex, Ebstein malformation, rapid anterograde conduction (APERP, SPERRI, or SPPCL≤250 ms), multiple pathways, and inducible atrial fibrillation. Of case subjects, 60 of 86 (69%) had≥2 EPS risk stratification components performed; 22 of 60 (37%) did not have EPS-determined high-risk characteristics, and 15 of 60 (25%) had neither concerning pathway characteristics nor inducible atrioventricular reciprocating tachycardia.CONCLUSIONS: Young patients may experience LTE from WPW syndrome without prior symptoms or markers of high-risk on EPS.

  View details for PubMedID 30067481

• Antibiotic Prophylaxis Practices in Pediatric Cardiac Implantable Electronic Device Procedures: A Survey of the Pediatric And Congenital Electrophysiology Society (PACES). Pediatric cardiology Chen, S. Y., Ceresnak, S. R., Motonaga, K. S., Trela, A., Hanisch, D., Dubin, A. M. 2018

  Abstract

  Cardiac implantable electronic device (CIED) infections are associated with significant morbidity in the pediatric device population, with a tenfold higher risk of infection in children compared to adults. The 2010 American Heart Association (AHA) guidelines recommend a single dose of systemic antibiotic (ABX) prophylaxis prior to CIED implantation and no post-operative (OP) ABX. However, there is limited data regarding adherence to this recommendation among the pediatric community. To assess current clinical practices for CIED ABX prophylaxis in pediatrics; whether the AHA guidelines are being followed; and if not, the reasons for non-adherence. An anonymous web-based survey was sent to physician members of the Pediatric And Congenital Electrophysiology Society regarding ABX prophylaxis for new CIED implants and reoperations. 75 (25%) members responded. Only 7% of respondents follow the 2010 AHA guidelines. While all respondents give pre-OP IV ABX, 64% routinely treat patients with 24-h post-OP IV ABX with additional oral or IV therapy. 69% of respondents are cognizant of the guidelines but 88% of those cognizant do not follow the guidelines for a variety of reasons including lack of data and different substrate (pediatric patients). 79% stated that pediatric-specific data would be required for them to change their practice and follow the published guidelines. The majority of pediatric EP physicians who responded to this survey do not follow the current AHA guidelines on ABX prophylaxis and administer post-OP ABX. Most pediatric EP physicians believe that the increased risk of infection in children merits additional ABX.

  View details for PubMedID 29564522

• Bridge to success: A better method of cryoablation for atrioventricular nodal reentrant tachycardia in children HEART RHYTHM Reddy, C. D., Ceresnak, S. R., Motonaga, K. S., Avasarala, K., Feller, C., Trela, A., Hanisch, D., Dubin, A. M. 2017; 14 (11): 1649–54

  Abstract

  Cryoablation for atrioventricular nodal reentrant tachycardia (AVNRT) is associated with higher recurrence rates than radiofrequency ablation (RFA). Junctional tachycardia marks procedural success with RFA, but no such indicator exists for cryoablation.The purpose of this study as to determine the impact of voltage mapping plus longer ablation lesions on midterm success of cryoablation for children with AVNRT.We performed a single-center retrospective analysis of pediatric patients with AVNRT who underwent cryoablation from 2011 to 2015. Patients ablated using a standard electroanatomic approach (control) were compared with patients ablated using voltage mapping (voltage group). In the voltage group, EnSite NavX navigation and visualization technology (St Jude Medical, St Paul, MN) was used to develop a "bridge" of lower voltage gradients (0.3-0.8 mV) of the posteroseptal right atrium to guide cryoablation. Kaplan-Meier analysis was used to determine freedom from recurrence of supraventricular tachycardia.In all, 122 patients were included (71 voltage, 51 control). There was no difference between groups regarding age, sex, or catheter-tip size. Short-term success was similar in both groups (98.5% voltage vs 92% control; P = .159), but recurrence rates were lower in the voltage group (0% vs 11%, P = .006). Follow-up time was shorter in the voltage group (15 ± 7 months vs 22 ± 17 months, P < .05). The 1-year freedom from recurrence was lower in the voltage group (100% vs 91.5%, P <.05). Ablation times were longer in the voltage group (43.7 ± 20.9 minutes vs 34.3 ± 20.5 minutes, P = .01), but overall procedure times were shorter in the voltage group (157 ± 40 minutes vs 198 ± 133 minutes; P = .018). No significant complication was seen in either group.Voltage gradient mapping and longer lesion time can decrease recurrence rates in pediatric patients with AVNRT.

  View details for PubMedID 28716699

• A multicenter review of ablation in the aortic cusps in young people. Pacing and clinical electrophysiology : PACE Nguyen, M. B., Ceresnak, S. R., Janson, C. M., Fishberger, S. B., Love, B. A., Blaufox, A. D., Motonaga, K. S., Dubin, A. M., Nappo, L., Pass, R. H. 2017

  Abstract

  Ablation within the aortic cusp is safe and effective in adults. There are little data on aortic cusp ablation in the pediatric literature. We investigated the safety and efficacy of aortic cusp ablation in young patients.A retrospective, descriptive study of aortic cusp ablation in five pediatric electrophysiology centers from 2008 to 2014 was performed. All patients <21 years of age who underwent ablation in the aortic cusps were included. Factors analyzed included patient demographics, procedural details, outcomes, and complications.Thirteen patients met inclusion criteria (median age 16 years [range 10-20.5] and median body surface area 1.58 m(2) [range 1.12-2.33]). Substrates for ablation included: nine premature ventricular contractions or sustained ventricular tachycardia (69%), two concealed anteroseptal accessory pathways (APs) (15%), one Wolff-Parkinson-White with an anteroseptal AP (8%), and one ectopic atrial tachycardia (8%). Three-dimensional electroanatomic mapping in combination with fluoroscopy was used in 12/13 (92%) patients. Standard 4-mm-tip radiofrequency (RF) current was used in 11/13 (85%) and low-power irrigated-tip RF in 2/13 (15%). Angiography was used in 13/13 and intracardiac echocardiography was additionally utilized in 3/13 (23%). Ablation locations included: eight noncoronary (62%), three left (23%), and two right (15%) cusps. Ablation was acutely successful in all patients. At median follow-up of 20 months, there was one recurrence of PVCs (8%). There were no ablation-related complications and no valvular injuries observed.Arrhythmias originating from the coronary cusps in this series were successfully and safely ablated in young people without injury to the coronary arteries or the aortic valve.

  View details for DOI 10.1111/pace.13126

  View details for PubMedID 28568013

• Ventricular pacing in single ventricles-A bad combination. Heart rhythm Bulic, A., Zimmerman, F. J., Ceresnak, S. R., Shetty, I., Motonaga, K. S., Freter, A., Trela, A. V., Hanisch, D., Russo, L., Avasarala, K., Dubin, A. M. 2017; 14 (6): 853-857

  Abstract

  Chronic ventricular pacing (VP) is associated with systolic dysfunction in a subset of pediatric patients with heart block and structurally normal hearts. The effect of chronic VP in congenital heart disease is less well understood, specifically in the single-ventricle (SV) population.To determine the longitudinal effect of VP in SV patients.SV patients with heart block and dual-chamber pacemakers requiring >50% VP were compared with nonpaced (controls) SV patients matched for age, sex, and SV morphology. Patients were excluded if a prepacing echocardiogram was not available. Echocardiogram and clinical parameters were compared at baseline (prepacing) and at last follow-up in the paced group, and in controls when they were at ages similar to those of their paced-group matches.Twenty-two paced and 53 control patients from 2 institutions were followed for similar durations (6.6±5 years vs 7.6±7.6 years; P = .59). There was no difference between groups regarding baseline ventricular function or the presence of moderate-to-severe atrioventricular valvar regurgitation (AVVR). Paced patients were more likely to develop moderate-to-severe systolic dysfunction (68% vs 15%; P < .01) and AVVR (55% vs 8%; P < .001) and require heart failure medications (65% vs 21%; P < .001). Chronic VP was also associated with a higher risk of transplantation or death (odds ratio, 4.9; 95% confidence interval, 1.05-22.7; P = .04).SV patients requiring chronic VP are at higher risk of developing moderate-to-severe ventricular dysfunction and AVVR with an increased risk of death or transplantation compared with controls. New strategies to either limit VP or improve synchronization in this vulnerable population is imperative.

  View details for DOI 10.1016/j.hrthm.2017.03.035

  View details for PubMedID 28528723

• Beta-blocker therapy for long QT syndrome and catecholaminergic polymorphic ventricular tachycardia: Are all beta-blockers equivalent? Heart rhythm Ackerman, M. J., Priori, S. G., Dubin, A. M., Kowey, P., Linker, N. J., Slotwiner, D., Triedman, J., Van Hare, G. F., Gold, M. R. 2017; 14 (1): e41-e44

  View details for DOI 10.1016/j.hrthm.2016.09.012

  View details for PubMedID 27659101

• Tachycardia cycle and atrioventricular nodal conduction properties in children with supraventricular tachycardia. Pacing and clinical electrophysiology : PACE Mills, M., Dubin, A. M., Motonaga, K. S., Ceresnak, S. R. 2017; 40 (6): 745–47

  View details for PubMedID 28383202

• Beta-blocker therapy for long QT syndrome and catecholaminergic polymorphic ventricular tachycardia: Are all beta-blockers equivalent? HEART RHYTHM Ackerman, M. J., Priori, S. G., Dubin, A. M., Kowey, P., Linker, N. J., Slotwiner, D., Triedman, J., Van Hare, G. F., Gold, M. R. 2017; 14 (1): E41-E44

  View details for DOI 10.1016/j.hrthm.2016.09.012

  View details for Web of Science ID 000396433000006

• Early somatic mosaicism is a rare cause of long-QT syndrome PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Priest, J. R., Gawad, C., Kahlig, K. M., Yu, J. K., O'Hara, T., Boyle, P. M., Rajamani, S., Clark, M. J., Garcia, S. T., Ceresnak, S., Harris, J., Boyle, S., Dewey, F. E., Malloy-Walton, L., Dunn, K., Grove, M., Perez, M. V., Neff, N. F., Chen, R., Maeda, K., Dubin, A., Belardinelli, L., West, J., Antolik, C., Macaya, D., Quertermous, T., Trayanova, N. A., Quake, S. R., Ashley, E. A. 2016; 113 (41): 11555-11560

  Abstract

  Somatic mosaicism, the occurrence and propagation of genetic variation in cell lineages after fertilization, is increasingly recognized to play a causal role in a variety of human diseases. We investigated the case of life-threatening arrhythmia in a 10-day-old infant with long QT syndrome (LQTS). Rapid genome sequencing suggested a variant in the sodium channel NaV1.5 encoded by SCN5A, NM_000335:c.5284G > T predicting p.(V1762L), but read depth was insufficient to be diagnostic. Exome sequencing of the trio confirmed read ratios inconsistent with Mendelian inheritance only in the proband. Genotyping of single circulating leukocytes demonstrated the mutation in the genomes of 8% of patient cells, and RNA sequencing of cardiac tissue from the infant confirmed the expression of the mutant allele at mosaic ratios. Heterologous expression of the mutant channel revealed significantly delayed sodium current with a dominant negative effect. To investigate the mechanism by which mosaicism might cause arrhythmia, we built a finite element simulation model incorporating Purkinje fiber activation. This model confirmed the pathogenic consequences of cardiac cellular mosaicism and, under the presenting conditions of this case, recapitulated 2:1 AV block and arrhythmia. To investigate the extent to which mosaicism might explain undiagnosed arrhythmia, we studied 7,500 affected probands undergoing commercial gene-panel testing. Four individuals with pathogenic variants arising from early somatic mutation events were found. Here we establish cardiac mosaicism as a causal mechanism for LQTS and present methods by which the general phenomenon, likely to be relevant for all genetic diseases, can be detected through single-cell analysis and next-generation sequencing.

  View details for DOI 10.1073/pnas.1607187113

  View details for PubMedID 27681629

• Is There a Difference in Tachycardia Cycle Length during SVT in Children with AVRT and AVNRT? Pacing and clinical electrophysiology : PACE Mills, M. F., Motonaga, K. S., Trela, A., Dubin, A. M., Avasarala, K., Ceresnak, S. R. 2016

  Abstract

  There are limited adult data suggesting the tachycardia cycle length (TCL) of atrioventricular reentry tachycardia (AVRT) is shorter than atrioventricular nodal reentry tachycardia (AVNRT), though little data exist in children. We sought to determine if there is a difference in TCL between AVRT and AVNRT in children.A single-center retrospective review of children with supraventricular tachycardia (SVT) from 2000 to 2015 was performed.Age ≤ 18 years, invasive electrophysiology study (EPS) confirming AVRT or AVNRT.Atypical AVNRT, congenital heart disease, antiarrhythmic medication use at time of EPS. Data were compared between patients with AVRT and AVNRT via t-test, χ(2) test, and linear regression.A total of 835 patients were included (12 ± 4 years, 52 ± 31 kg, TCL 321 ± 55 ms), 539 (65%) with AVRT (270 Wolff-Parkinson-White, 269 concealed pathways) and 296 (35%) with AVNRT. Patients with AVRT were younger (11.7 ± 4.1 years vs 13.0 ± 3.6 years, P < 0.001) and smaller (49 ± 22 kg vs 57 ± 43 kg, P < 0.001). In the baseline state, the TCL was shorter in AVRT than AVRNT (329 ± 51 ms vs 340 ± 60 ms, P = 0.04). In patients requiring isoproterenol to induce SVT, there was no difference in TCL (290 ± 49 ms vs 297 ± 49 ms, P = 0.26). When controlling for age, there was no difference in TCL between AVRT and AVNRT at baseline or on isoproterenol. The regression equation for TCL in the baseline state was TCL = 290 + 4 (age), indicating the TCL will increase by 4 ms above a baseline of 290 ms for each year of life.When controlling for age, there is no difference in the TCL between AVRT and AVNRT in children. Age, not tachycardia mechanism, is the most significant factor in predicting TCL.

  View details for DOI 10.1111/pace.12950

  View details for PubMedID 27653639

• 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

• Risk of cardiac disease and observations on lack of potential predictors by clinical history among children presenting for cardiac evaluation of mid-exertional syncope CARDIOLOGY IN THE YOUNG Miyake, C. Y., Motonaga, K. S., Fischer-Colbrie, M. E., Chen, L., Hanisch, D. G., Balise, R. R., Kim, J. J., Dubin, A. M. 2016; 26 (5): 894-900

  Abstract

  This study aimed to evaluate the incidence of cardiac disorders among children with mid-exertional syncope evaluated by a paediatric cardiologist, determine how often a diagnosis was not established, and define potential predictors to differentiate cardiac from non-cardiac causes. Study design We carried out a single-centre, retrospective review of children who presented for cardiac evaluation due to a history of exertional syncope between 1999 and 2012. Inclusion criteria included the following: (1) age ⩽18 years; (2) mid-exertional syncope; (3) electrocardiogram, echocardiogram and an exercise stress test, electrophysiology study, or tilt test, with exception of long QT, which did not require additional testing; and (4) evaluation by a paediatric cardiologist. Mid-exertional syncope was defined as loss of consciousness in the midst of active physical activity. Patients with peri-exertional syncope immediately surrounding but not during active physical exertion were excluded.A total of 60 patients met the criteria for mid-exertional syncope; 32 (53%) were diagnosed with cardiac syncope and 28 with non-cardiac syncope. A majority of cardiac patients were diagnosed with an electrical myopathy, the most common being Long QT syndrome. In nearly half of the patients, a diagnosis could not be established or syncope was felt to be vasovagal in nature. Neither the type of exertional activity nor the symptoms or lack of symptoms occurring before, immediately preceding, and after the syncopal event differentiated those with or without a cardiac diagnosis.Children with mid-exertional syncope are at risk for cardiac disease and warrant evaluation. Reported symptoms may not differentiate benign causes from life-threatening disease.

  View details for DOI 10.1017/S1047951115001481

  View details for PubMedID 26277987

• 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 Web of Science ID 000372367800012

  View details for PubMedCentralID PMC4770895

• 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 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

• Automated detection of ventricular pre-excitation in pediatric 12-lead ECG JOURNAL OF ELECTROCARDIOLOGY Gregg, R. E., Zhou, S. H., Dubin, A. M. 2016; 49 (1): 37-41

  Abstract

  With increased interest in screening of young people for potential causes of sudden death, accurate automated detection of ventricular pre-excitation (VPE) or Wolff-Parkinson-White syndrome (WPW) in the pediatric resting ECG is important. Several recent studies have shown interobserver variability when reading screening ECGs and thus an accurate automated reading for this potential cause of sudden death is critical. We designed and tested an automated algorithm to detect pediatric VPE optimized for low prevalence.Digital ECGs with 12 leads or 15 leads (12-lead plus V3R, V4R and V7) were selected from multiple hospitals and separated into a testing and training database. Inclusion criterion was age less than 16 years. The reference for algorithm detection of VPE was cardiologist annotation of VPE for each ECG. The training database (n=772) consisted of VPE ECGs (n=37), normal ECGs (n=492) and a high concentration of conduction defects, RBBB (n=232) and LBBB (n=11). The testing database was a random sample (n=763). All ECGs were analyzed with the Philips DXL ECG Analysis algorithm for basic waveform measurements. Additional ECG features specific to VPE, mainly delta wave scoring, were calculated from the basic measurements and the average beat. A classifier based on decision tree bootstrap aggregation (tree bagger) was trained in multiple steps to select the number of decision trees and the 10 best features. The classifier accuracy was measured on the test database.The new algorithm detected pediatric VPE with a sensitivity of 78%, a specificity of 99.9%, a positive predictive value of 88% and negative predictive value of 99.7%.This new algorithm for detection of pediatric VPE performs well with a reasonable positive and negative predictive value despite the low prevalence in the general population.

  View details for DOI 10.1016/j.jelectrocard.2015.08.006

  View details for Web of Science ID 000368320700008

• 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. 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

• 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

  View details for PubMedID 25769637

• 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

• 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 PubMedID 25828598

• Wolff-Parkinson-White syndrome (WPW) and athletes: Darwin at play? JOURNAL OF ELECTROCARDIOLOGY Ceresnak, S. R., Dubin, A. M. 2015; 48 (3): 356-361

  View details for DOI 10.1016/j.jelectrocard.2014.12.019

  View details for Web of Science ID 000354343100012

  View details for PubMedID 25722079

• 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

  View details for PubMedID 25600208

• 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 PubMedID 25433143

• Automated detection of ventricular pre-excitation in pediatric 12-lead ECG. Journal of electrocardiology Gregg, R. E., Zhou, S. H., Dubin, A. M. 2015; 49 (1): 37–41

  Abstract

  With increased interest in screening of young people for potential causes of sudden death, accurate automated detection of ventricular pre-excitation (VPE) or Wolff-Parkinson-White syndrome (WPW) in the pediatric resting ECG is important. Several recent studies have shown interobserver variability when reading screening ECGs and thus an accurate automated reading for this potential cause of sudden death is critical. We designed and tested an automated algorithm to detect pediatric VPE optimized for low prevalence.Digital ECGs with 12 leads or 15 leads (12-lead plus V3R, V4R and V7) were selected from multiple hospitals and separated into a testing and training database. Inclusion criterion was age less than 16 years. The reference for algorithm detection of VPE was cardiologist annotation of VPE for each ECG. The training database (n=772) consisted of VPE ECGs (n=37), normal ECGs (n=492) and a high concentration of conduction defects, RBBB (n=232) and LBBB (n=11). The testing database was a random sample (n=763). All ECGs were analyzed with the Philips DXL ECG Analysis algorithm for basic waveform measurements. Additional ECG features specific to VPE, mainly delta wave scoring, were calculated from the basic measurements and the average beat. A classifier based on decision tree bootstrap aggregation (tree bagger) was trained in multiple steps to select the number of decision trees and the 10 best features. The classifier accuracy was measured on the test database.The new algorithm detected pediatric VPE with a sensitivity of 78%, a specificity of 99.9%, a positive predictive value of 88% and negative predictive value of 99.7%.This new algorithm for detection of pediatric VPE performs well with a reasonable positive and negative predictive value despite the low prevalence in the general population.

  View details for PubMedID 26320370

• 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.hrthm.2014.09.056

  View details for PubMedID 25277988

• 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

• 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

• 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.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

• 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

• 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

  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 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): e55-78

  View details for DOI 10.1016/j.hrthm.2014.05.010

  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 PubMedID 24799504

• 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

  View details for PubMedID 24456371

• 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 PubMedID 24332245

• 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

• 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

  View details for DOI 10.1016/j.hfc.2013.09.011

  View details for PubMedID 24275296

• 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

• 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

  View details for PubMedID 24076489

• 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 PubMedID 23993128

• The effects of ketamine on dexmedetomidine-induced electrophysiologic changes in children. Paediatric anaesthesia 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 PubMedID 23506472

• 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 PubMedID 23932443

• 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 PubMedID 23748209

• 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

• 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

• 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 PubMedID 23667268

• 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

  View details for PubMedID 23437865

• 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. 2013

  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 PubMedID 23764088

• 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 PubMedID 22682994

• Update on pacing and implantable cardioverter defibrillators in children PROGRESS IN PEDIATRIC CARDIOLOGY Dubin, A. M. 2012; 33 (2): 177–81

  View details for DOI 10.1016/j.ppedcard.2012.02.011

  View details for Web of Science ID 000213525900011

• 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? 32nd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation / Meeting of the ISHLT Academy - Core Competencies in Mechanical Circulatory Support 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 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 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 PubMedID 20693934

• 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

• Electrical Dyssynchrony in Pediatric Pulmonary Arterial Hypertension 31st Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) 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

• Electrophysiology Issues and Heart Failure in Congenital Heart Disease HEART FAILURE IN CONGENITAL HEART DISEASE: FROM FETUS TO ADULT Ceresnak, S. R., Dubin, A. M., Shaddy, R. E. 2011: 155–72

  View details for DOI 10.1007/978-1-84996-480-7_8

  View details for Web of Science ID 000286092100008

• 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

• 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

• 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 PubMedID 20514553

• 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

• Recommendations from the Heart Rhythm Society Task Force on Lead Performance Policies and Guidelines HEART RHYTHM Maisel, W. H., Hauser, R. G., Hammil, S. C., Ellenbogen, K. A., Epstein, A. E., Hayes, D. L., Alpert, J. S., Berger, R. D., Curtis, A. B., Dubin, A. M., Estes, N., Gura, M. T., Krahn, A. D., Lampert, R., Lindsay, B. D., Wilkoff, B. L. 2009; 6 (6): 869–85

  View details for DOI 10.1016/j.hrthm.2009.04.024

  View details for Web of Science ID 000266658800028

  View details for PubMedID 19467518

• 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 58th Annual Scientific Session of the American-College-of-Cardiology 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 80th Annual Scientific Session of the American-Heart-Association (AHA) Chanani, N. K., Chiesa, N. A., Dubin, A. M., Avasarala, K., Van Hare, G. F., Collins, K. K. BLACKWELL PUBLISHING. 2008: 1152–59

  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

  View details for PubMedCentralID PMC2567118

• 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 PubMedID 18165557

• Device therapy in children Dubin, A. M. ELSEVIER IRELAND LTD. 2007: 14

  View details for Web of Science ID 000252310200053

• Cryoablation for atrioventricular nodal reentrant tachycardia (AVNRT) in 154 young patients: 4mm vs. 6mm catheter tip sizes Chanani, N. K., Chiesa, N. A., Dubin, A. M., Avasarala, K., Van Hare, G. F., Collins, K. K. LIPPINCOTT WILLIAMS & WILKINS. 2007: 514

  View details for Web of Science ID 000250394302352

• Midterm results of resynchronization therapy in pediatrics: Do we need new guidelines? Dubin, A. M., Collins, K. K., Van Hare, G. F., Reddy, V. M., Hanisch, D., Chiesa, N., Rosenthal, D. N. LIPPINCOTT WILLIAMS & WILKINS. 2007: 664

  View details for Web of Science ID 000250394303073

• 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

• Right ventricular mechanical dyssynchrony in children with hypoplastic left heart syndrome: A target for cardiac resynchronization therapy? Friedberg, M. K., Silverman, N. H., Dubin, A. M., Rosenthal, D. N. ELSEVIER SCIENCE INC. 2007: 257A

  View details for Web of Science ID 000244651801499

• 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

• A multicenter pediatric implantable cardioverter defibrillator retrospective registry Berul, C. I., Van Hare, G., 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. LIPPINCOTT WILLIAMS & WILKINS. 2006: 450

  View details for Web of Science ID 000241792803050

• 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

• Resynchronization in pediatrics - Who needs it? JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Dubin, A. M. 2005; 46 (12): 2290–91

  View details for DOI 10.1016/j.jacc.2005.09.004

  View details for Web of Science ID 000234090600019

  View details for PubMedID 16360060

• 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 32nd Annual Conference on Computers in Cardiology 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. IEEE. 2005: 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

• Radiofrequency ablation in congenital heart disease: A call to arms - Editorial commentary HEART RHYTHM Dubin, A. M. 2004; 1 (2): 174–75

  View details for DOI 10.1016/j.hrthm.2004.04.001

  View details for Web of Science ID 000225715600007

  View details for PubMedID 15851149

• Validation of simulation-based training in neonatal resuscitation: Use of heart rate variability as marker for mental workload Annual Meeting of the Pediatric-Academic-Societies 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

• Use of resynchronization therapy in pediatric patients with congenital heart disease and complete heart block Rosenthal, D. N., Dubin, A. M., Geiss, D. M., Reddy, V. M., Shah, J. J., Bash, S. E., Zimmerman, F. J. ELSEVIER SCIENCE INC. 2004: 384A

  View details for DOI 10.1016/S0735-1097(04)91621-X

  View details for Web of Science ID 000189388501623

• 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 76th Annual Scientific Session of the American-Heart-Association 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: 494–94

  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 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 22nd Annual Meeting of the North-American-Society-of-Pacing-and-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. WILEY-BLACKWELL PUBLISHING, INC. 2002: 1009–14

  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 27th Annual ISCE Conference on Research and Technology Transfer in Computerized Electrocardiology Van Hare, G. F., Dubin, A. M., Collins, K. K. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2002: 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 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

• 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: 322–22

  View details for Web of Science ID 000171895001539

• 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: 745–45

  View details for Web of Science ID 000171895003488

• 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

• WPW in the pediatric population: Are we assessing risk adequately? Dubin, A. M., Collins, K. K., Chiesa, N., Hanisch, D., Van Hare, G. F. ELSEVIER SCIENCE INC. 2001: 468A

  View details for Web of Science ID 000166914402125

• 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 26th Annual ISCE Conference 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

• QTc interval in infants treated with cisapride Kikkert, M. A., Dubin, A. M., Mirmiran, M., Ariagno, R. L. INT PEDIATRIC RESEARCH FOUNDATION, INC. 2000: 45A

  View details for Web of Science ID 000086155300264

• 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

• Outcome between listing and transplantation in pediatric heart transplant candidates: Comparison of congenital heart disease and dilated cardiomyopathy Dubin, A. M., Rosenthal, D. N., Chin, C., Falco, D. A., Gamberg, P., Bernstein, D. INT PEDIATRIC RESEARCH FOUNDATION, INC. 1999: 22A

  View details for DOI 10.1203/00006450-199904020-00135

  View details for Web of Science ID 000079476700119

• Prolongation of QTc in infants treated with cisapride Dubin, A. M., Van Hare, G. F., Mirmiran, M., Baldwin, R. B., Ariagno, R. L. INT PEDIATRIC RESEARCH FOUNDATION, INC. 1999: 22A

  View details for DOI 10.1203/00006450-199904020-00136

  View details for Web of Science ID 000079476700120

• Relationship of QT interval, sleep position and sleep state in preterm infants Dubin, A. M., Adams, M., Van Hare, G. F., Mirmiran, M., Baldwin, R. B., Ariagno, R. L. INT PEDIATRIC RESEARCH FOUNDATION, INC. 1999: 194A

  View details for DOI 10.1203/00006450-199904020-01154

  View details for Web of Science ID 000079476701138

• 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: 766–67

  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