Research & Publications Research

Current Research Programs/Studies

COMIRB Protocol

COLORADO MULTIPLE INSTITUTIONAL REVIEW BOARD
CAMPUS BOX F-490    TELEPHONE:  303-724-1055  Fax:  303-724-0990    


Protocol #: 16-0931
Project Title: Subcutaneous Implantable Cardioverter Defibrillators in Pediatrics and Congenital Heart Disease: A Multicenter Review        
Principal Investigator: Johannes C von Alvensleben    
Version Date: 5/4/2017                            
  1. Hypotheses and Specific Aims:  The eligibility of pediatric patients and those with congenital heart disease (CHD) patients for subcutaneous implantable cardioverter defibrillator (S-ICD) is not fully known. The aim of this study was to determine in these patients:
    1. Short and midterm outcomes including complications, appropriate/inappropriate shocks, and effect of newer device generations
    2. Evaluate the effect of differing implantation techniques: subcutaneous 2- and 3-incision technique, axillary position, and submuscular/subfascial implantation.  
  2. Background and Significance: Implantable cardioverter defibrillators (ICDs) reduce the risk of sudden death in individuals at high risk of ventricular arrhythmias.1,2 Conventional ICD systems use a transvenous lead for sensing of ventricular arrhythmias and delivery of ICD therapy. The placement of transvenous leads may be complicated by pneumothorax, venous damage, cardiac perforation, and lead displacement. In the longer term, transvenous ICD systems are susceptible to lead fracture, infection, and venous obstruction.3–5 Removal of failed or infected transvenous leads is associated with considerable morbidity and mortality.6 Transvenous lead-related problems are a particular issue in younger patients due to ongoing growth, physical activity, and a long life expectancy over which patients are exposed to the risk of complications.
    An entirely subcutaneous ICD (S-ICD, Boston Scientific, Marlborough, MA, USA), comprising the SQ-RX pulse generator and the Q-TRAK subcutaneous lead, has been developed and is now commercially available. The S-ICD has no intravascular components and may therefore avoid many of the complications associated with transvenous leads. The manner in which a subcutaneous signal is detected is completely different from that of an endocardial signal and eligibility for the device is primarily based on whether a patient’s surface electrograms fall within a manufacturer specified algorithm. Implantation is preceded by a screening test during which skin electrodes are positioned at the level of the 3 projected sensing sites (the 2 electrodes and the pulse generator unit). Ten seconds of ECG are recorded from these surface equivalents in supine and standing positions, at rest and after exercise, in order to validate at least one of the sense vectors allowing an acceptable ratio between R-wave and T-wave amplitudes. The choice of the optimal vector is made automatically by the device but can be changed manually.
    As described, the primary eligibility requirement for a S-ICD is an appropriate R- and T-wave relationship that matches a device algorithm. Other exclusion criteria include pacemaker-dependent patients or those requiring biventricular resynchronization, and patients with sustained ventricular tachycardia episodes susceptible to be treated with anti-tachycardia pacing. Adult trials, such as the EFFORTLESS-SICD trial, have demonstrated that the characteristics of patients included in S-ICD studies significantly differ from patients included in transvenous ICD studies.7 Specifically that they are younger and a higher proportion of patients with congenital heart disease. Despite this suggestion, however, only small studies or isolated clinical cases have been specifically conducted in children and/or patients with congenital heart disease.  While sample sizes were limited, these studies nonetheless identified certain key findings. Different anatomical relationships are commonly found in this subgroup of patients, including right or left ventricular hypertrophy and wide T waves, all conditions that can vary the ratio between R-wave and T-wave amplitudes and therefore affect eligibility for implantation. In a dedicated study specifically addressing this issue involving 30 patients with adult congenital heart disease, eligibility was nevertheless relatively high at 87%.8
    Finally, , several implantation techniques have emerged and their effect in pediatric patients is not known.  
  3. Preliminary Studies/Progress Report:  None
  4. Research Methods
    1. Outcome Measure(s): Multicenter retrospective cohort study of all pediatric patients and those with congenital heart disease who underwent placement of a S-ICD. Patient demographics, screening parameters, and follow-up information will be collected.
    2. Description of Population to be Enrolled:  Pediatric patients (considered newborn to age <21 yrs) and those with congenital heart disease (including adult patients) who underwent implantation of a SICD.
    3. Study Design and Research Methods: Retrospective multicenter center cohort study. Clinical and eligibility information for patients who previously underwent S-ICD will be abstracted and recorded.   
    4. Description, Risks and Justification of Procedures and Data Collection Tools: Data will be abstracted from the electronic medical record (EPIC) system at CHCO and from the electronic records of participating center by researchers with hospital approved access. Data will be entered into a RedCap database with CHCO being the primary site for database creation, management, and administration. Data will be de-identified and uploaded to the system by the site PI or designee. There is a rare risk of breach of confidentiality given the access to protect health information although reasonable safeguards will be implemented whenever possible.
    5. Potential Scientific Problems: None anticipated. Patients have been previously identified.
    6. Data Analysis Plan: This is a descriptive study. The characteristics of the patient population will be described as means, standard deviations, and ranges as appropriate.
    7. Summarize Knowledge to be Gained: S-ICDs may provide several advantages over transvenous ICDs in pediatric patients and those with congenital heart disease although the short and midterm outcomes are not known.
    8. References:
      1. Krahn AD, Lee DS, Birnie D, Healey JS, Crystal E, Dorian P, Simpson CS, et al. Predictors of short-term complications after implantable cardioverter-defibrillator replacement: Results from the Ontario ICD Database. Circ Arrhythm Electrophysiol 2011; 4:136–142.
      2. Birnie DH, Parkash R, Exner DV, Essebag V, Healey JS, Verma A, Coutu B, et al. Clinical predictors of fidelis lead failure: Report from the canadian heart rhythm society device committee. Circulation 2012; 125:1217–1225.
      3. Lickfett L, Bitzen A, Arepally A, Nasir K, Wolpert C, Jeong KM, Krause U, et al. Incidence of venous obstruction following insertion of an implantable cardioverter defibrillator. A study of systematic contrast venography on patients presenting for their first elective ICD generator replacement. Europace 2004; 6:25–31.
      4. Hauser RG, Katsiyiannis WT, Gornick CC, Almquist AK, Kallinen LM. Deaths and cardiovascular injuries due to device-assisted implantable cardioverter-defibrillator and pacemaker lead extraction. Europace 2010; 12:395–401.
      5. Lambiase PD, Barr C, Dheuns DA et al,. EFFORTLESS Investigators. Worldwide experience with a totally subcutaneous implantable defibrillator: early results from the EFFORTLESS S-ICD Registry, Eur. Heart J 2014;34:1657–1665.
      6. Burke MC, Gold MR, Knight BP, et al. Safety and efficacy of the totally subcutaneous implantable defibrillator. JACC 2015; 65:1605-1615.
      7. Zeb M, Curzen N, Veldtman G, Yue A, Roberts P, Wilson D, et al. Potential eligibility of congenital heart disease patients for subcutaneous implantable cardioverter-defibrillator based on surface electrocardiogram mapping. Europace 2015;17:1059–1067.
      8. Pettit SJ, Mclean A, Colquhoun I, Connelly D, Mcleod K. Clinical experience of subcutaneous and transvenous implantable cardioverter defibrillators in children and teenagers. PACE 2013; 36:1532–1538.
 

Lone Atrial Fibrillation in Pediatric Patients: A Multi Institutional Retrospective PACES Study

PI: Peter Aziz
Research coordinator: Jaime Fensterl (fenstej@ccf.org)

Lone atrial fibrillation, defined as atrial fibrillation in the absence of underlying heart or systemic disease, has recently emerged and is increasingly encountered in the pediatric population. Current literature is limited by small sample size and retrospective study design and expert guidelines for pediatric patients are lacking. We have studied lone atrial fibrillation in children using a large clinical database and found that older children had high recurrence rates approaching 30-50% at one year. However, we were not able to assess the utility of EP ablation due to limitations inherent to the database and due to limited sample size. In this research project, our aim is to establish the largest series of pediatric lone atrial fibrillation patients to better understand their specific characteristics, identify risk factors for recurrence and to assess the utility of ablation therapy (SVT or AF) in reducing the recurrence rate. Our aim is to recruit patients from 10 sites at least by May 2018.

Inclusion criteria:
Patients who meet the following criteria will be included in the study:
  • Children < or equal to 21 years old at the time of diagnosis of lone atrial fibrillation (any AF in patients without clinical or echocardiographic evidence of any cardiopulmonary disease including hypertension6) between 2004 and 2015
  • Confirmed atrial fibrillation on a 12-lead ECG or Holter monitor
Exclusion criteria:
Patients who meet the following criteria should be excluded from the study
  • Thyroid disease
  • Any congenital heart disease
  • Cardiomyopathy
  • Open heart surgery
  • Hypertension
Primary outcome variable (s): Time to first recurrence of atrial fibrillation defined as any AF documented on ECG or Holter monitor.

If you are interested in this study, please contact Peter Aziz atazizp@ccf.org and Jaime Fensterl at fenstej@ccf.org for more information.

 

Intravenous Sotalol in Pediatric and Congenital Patients: A Multi-center Registry

Background:
Though intravenous (IV) sotalol has been used outside the US for over 30 years, it was only recently approved by the Food and Drug Administration (FDA; 2009) and reintroduced to the US market (2015).  Sotalol is a class III antiarrhythmic agent that prolongs action potential duration while also blocking beta-adrenergic receptors.  IV sotalol has been used for many different types of tachyarrhythmias with the distinct advantage of having an oral equivalent with more tolerable side effects (i.e., no ocular, hepatic, or endocrine effects).  This is of particular importance in pediatric patients as well as young adults with congenital heart disease who will likely remain on antiarrhythmic therapy for long periods of time (potentially a lifetime).  Additionally, collateral damage to developing organ systems by other class III antiarrhythmics makes sotalol an important alternative in this population.

IV sotalol is indicated for substitution of oral sotalol in patients who are unable to take oral medications.  Administration recommendations for this study are based on the FDA label, the adult and pediatric literature, and pharmacokinetic modeling by the University of Maryland. The adult literature reports infusion times between one (1) and thirty (30) minutes, most commonly five (5) minutes.1,2,3 Typical IV sotalol doses have been reported around 1-1.5 mg/kg/dose.4  Zhang et al5 report the use of IV sotalol in children with normal left ventricular function with a loading dose of 1.0 mg/kg over ten (10) minutes, followed by a maintenance dose of 4.5 mg/kg/day over twenty-four (24) hours. Li et al6 recently report the use of IV sotalol in a larger cohort of pediatric patients with a loading dose of 1.0 mg/kg over ten (10) minutes, followed by a continuous infusion over one (1) to twenty-four (24) hours. Pediatric dosing for IV sotalol requires further investigation.

The purpose of this multicenter prospective nonrandomized registry study is to evaluate the safety, efficacy, and dosing of IV sotalol in pediatric patients with tachyarrhythmias as well as adults with congenital heart disease.  

Our goal is to collect 300 patients from 30 centers, approximately 10 patients per center, over an 18 month time period.

Primary Aims:
Aim1. To study the safety of IV sotalol administration through monitoring of blood pressure, heart rate, telemetry, and frequent electrocardiograms.

We hypothesize that IV sotalol can be safely used to terminate atrial, ventricular and junctional tachyarrhythmias in the pediatric and congenital population. Administration of IV antiarrhythmics typically occurs in an intensive care unit, where there is continuous assessment of patient vital signs and rhythm.  Collected data will include heart rate (HR) and blood pressure (BP) before and at the end of treatment, as well as minimum and maximum values during infusion.  Additionally, electrocardiographic data, including QTc will be collected from enrolled patients. Safety markers will include events of bradycardia, sinus arrest, severe hypotension during treatment, treatment related arrhythmias, QTC prolongation >480ms, need for ionotropic support or escalation of support during treatment, and death. 

Aim2. To evaluate the efficacy of IV sotalol by assessing tachyarrhythmia termination, reduction or rate-control. 

We hypothesize that IV sotalol will be highly efficacious in the termination, reduction or rate-control for pediatric and congenital tachyarrhythmias.  Patients spanning the spectrum of tachyarrhythmias—atrial, junctional, and ventricular—will be included in the registry.  Efficacy will be assessed by monitoring telemetry and EKGs with data input for rate and rhythm before, during, and after infusions.  Additionally, other potential patient effects that may occur will be noted.  Efficacy markers will include successful termination, time to termination, and recurrence.

Aim3.  To report the clinically employed effective dose and rate of administration for IV sotalol.

We hypothesize that patient clinical status, coupled with clinical judgment will influence the dose and rate of IV sotalol administration.  Given that this is a registry study, there will not be a prescriptive protocol for drug administration; rather, data collected will include the amount of drug administered (calculated in mg/kg, mg/m2) and the rate of administration (over minutes-hours).  For the purposes of analysis, rates of administration will be stratified as short (<1 hour), intermediate (1-4 hours) and long (≥5 hours).  Data collected will include patient clinical status pre and post drug infusion.

Protocol:
Once eligible patients have been identified (please see below inclusion/exclusion criteria), participating centers will complete an online data collection form. The primary site for online database creation, management and administration will be West Virginia University.  Data collected at participating sites will be de-identified and uploaded to the system by either site PI or designee. 

Demographic & Clinical Parameters:
  • Age, sex, height, weight
  • Heart rate
  • Blood pressure
  • EKG parameters (PR, QRSd, QT, QTc)
  • Echocardiogram parameters (Fractional Shortening, EF, qualitative estimate)
  • Arrhythmia diagnosis (provide de-identified scanned EKG, 12 lead or rhythm strip for investigator review)
  • Arrhythmia type (paroxysmal, sustained, non-sustained, incessant, intermittent sustained, intermittent non-sustained)
  • Additional diagnoses
  • Symptoms
  • Prior antiarrhythmic treatment (drug with outcome, ablation)
  • Heart rate at initiation of treatment
  • Arrhythmia duration prior to the initiation of treatment
  • Reason for IV sotalol use
  • Dose of IV sotalol (total dose, dose per kg, dose per m2)
  • Duration of infusion
  • Hemodynamic data before, during and after administration
  • Result of IV sotalol administration (arrhythmia outcome, time to termination, recurrence, QTC/PR/HR maximum at the end of infusion, BP minimum at the end of infusion, need to slow or terminate infusion early, symptoms post infusion, recurrence, time of recurrence)
  • Patient outcome
  • Follow up (single dose only, subsequent periodic administration vs. infusion, transition to oral sotalol)
  • Other effects reported
Inclusion Criteria:
Patients who meet the following criteria will be eligible for participation in this study:
  1. All ages included, with a subgroup analysis for adults with congenital heart disease.  Pediatric patients are defined as newborn to age 18.
  2. Patients with a tachyarrhythmia including: supraventricular tachycardia, atrial ectopy, atrial tachycardia, atrial fibrillation, junctional ectopic tachycardia, ventricular ectopy, and ventricular tachycardia.
     
Exclusion Criteria:
  1. Patients who do not meet inclusion criteria will be excluded.
Safety Considerations Prior to Administration:
Since this is a registry study on clinical use, there are no specific exclusion criteria, but the following findings related to safety of administration should be considered prior to use:
  1. LVEF <50% by echocardiogram prior to administration
  2. Sinus bradycardia for age or condition, sick sinus syndrome or second and third degree AV block unless functional pacing wires are present (either permanent or temporary)
  3. Congenital or acquired long QT syndromes
  4. QTc (Bazett’s) >450 msec (in the presence of narrow complex QRS, or adjusted for the QRS duration, consider JTc)
  5. Decreased creatinine clearance <40 mL/min (sotalol dose adjustments recommended)
  6. Cardiogenic shock or decompensated heart failure
  7. Bronchial asthma or related bronchospastic conditions
  8. Known hypersensitivity to sotalol
Previously Published Data & Recommendations for Administration:
  • FDA label
    • 5 hour infusion (based on similar bioavailability and pharmacokinetics to oral; no clinical studies)
  • Data in the adult and pediatric literature support the following
    • Doses of 1-1.5 mg/kg, or 95% of an oral dose
    • Bolus (acute administration in the cath lab with intensive monitoring)1,2
    • 5 minutes (acute administration in the cath lab with intensive monitoring)1,2
    • 10 minutes (Zhang et al)5
    • 10 minutes (Li et al)6
    • 30 minutes (multiple studies)3
    • >30 minutes
  • Pharmacokinetic Modeling Data (University of Maryland School of Pharmacy Center for Translational Medicine)
    • 2 hours of infusion of IV sotalol provides nearly identical profile to oral sotalol in simulated data
      • 1.5 minutes yields similar maximum concentrations to 160 mg PO BID
    • Loading protocols for IV/PO load:
      • 40 mg over 2 hours followed immediately by 80 mg PO BID yields nearly equivalent levels to the steady state reached after 72 hours after the first PO dose
      • 60 mg over 2 hours followed immediately by 120 mg PO BID yields nearly equivalent levels to the steady state reached after 72 hours after the first PO dose (QTc can be checked after 1 hour of 30 mg during the load to assure safety)
      • 80 mg over 2 hours followed immediately by 160 mg PO BID yields nearly equivalent levels to the steady state reached after 72 hours after the first PO dose (QTc can be checked after 1 hour of 40 mg during the load to assure safety)
  • Monitoring
    • Data in the literature suggest that in postoperative adults, cardiac output decreases moderately due to a reduction in heart rate.  However, in other settings any reductions in blood pressure seem to be of minor significance in most patients.  In both published pediatric studies of IV sotalol, the drug was only administered after an echocardiogram demonstrated an EF >50%.
The following might be considered:
  • Some prior knowledge of systemic ventricular function before administration.
  • In early postoperative patients, monitoring of arterial pressure with an indwelling catheter is probably prudent.
  • Sotalol is a beta-blocker, so administration during concomitant administration of catecholamines or ionotropes should probably be done with caution.
  • Frequent blood pressure monitoring is reasonable in all patients during any initial IV sotalol dose.
  • Frequent blood pressure monitoring is reasonable in all patients during any administration over ≤1 hour.
Data Analyses:
We intend to use SAS software for statistical analysis.  We will use mean values +/- standard error with confidence intervals, and proportions with confidence intervals.  To look at the difference in time to termination compared to administration rate we will use either Kaplan Meier curves and/or ANOVA comparisons using a p value <0.05 as significant.

Sample size:  With a sample size of 300 patients, approximately 10 patients per center, we will have good precision for estimating the reported safety concern, proportion of patients with QTc prolongation and the efficacy marker, proportion of patients that terminated.  For example if we found that 8% of the patients had QTc prolongation, the 95% confidence interval for the proportion would be (5.4%, to 11.7%) and if the proportion of patients that terminated was found to be 69%, the 95% CI would be (63.5% to 74.0%). 
    
Grant Support:
For the first 30 sites, investigators may request to receive an unrestricted educational grant of $5,000 per participating site to support IRB fees, study coordinator fees, “per patient” reimbursement, data collection and other study-related expenses.  

If you're interested, please submit a request via email for an unrestricted educational grant to support an investigator initiated clinical trial on your institution’s letterhead, to: Lindsey Malloy-Walton at lemalloywalton@cmh.edu. Please title the Subject line of your email: “IV sotalol registry grant request – Name of your Institution

Upon approval, 50% of the grant will be disbursed to the site. The remaining 50% of the grant will be disbursed once the site has submitted its first (1st) Patient Data Collection Form to the WVU data center.

The WVU data center will prepare a monthly report specifying the date each site’s first (1st) Patient Data Collection Form is received in order for disbursement of the remaining 50% of the grant to the site.  The WVU data center will ensure all Patient Data Collection Forms are properly submitted and logged.  



Participating Sites:
Study Site Eligibility:
Pediatric hospitals that have administered IV sotalol to at least one (1) patient are eligible to participate in this study.

Total Number of Study Sites:
This study will enroll patients from 30 pediatric hospitals.

PACES Related Matters:
Additionally, we used the Pediatric and Congenital Electrophysiology Society (PACES) pre-Heart Rhythm Society Scientific Sessions research meeting to propose the registry to the pediatric community at large again.  The registry is a PACES approved study.

Currently confirmed sites (with site Principal Investigator):
Site PI
Washington University SOM/St Louis Children’s Hospital, MO Jennifer N. Avari Silva, MD
Children’s Mercy Hospital, Kansas City, MO Lindsey Malloy-Walton, DO, MPH
West Virginia University, Morgantown, WV J. Philip Saul, MD
Oregon Health & Science University, Portland, OR Seshadri Balaji, MD, PhD

Steering committee for this study is as follows:
Name Site Title Role
Jennifer N. Avari Silva, MD Washington University School of Medicine, St Louis, MO Director, Pediatric EP
Assistant Professor, Pediatrics
Protocol creation, patient enrollment, data analysis, manuscript preparation
Lindsey Malloy-Walton, DO, MPH Children’s Mercy Hospital, UMKC, Kansas City, MO Assistant Professor, Pediatrics Protocol creation, patient enrollment, data analysis, manuscript preparation
J. Philip Saul, MD West Virginia University,Morgantown, WV Executive Vice President, Children’s Hospital
Professor , Pediatrics
Protocol creation, patient enrollment, data analysis, manuscript preparation

Writing committee:
Participating sites will each designate a single site PI who will participate in the preparation of the manuscript.  Each site that enrolls at least one patient over the 18 month study period may designate one member to the writing committee.


Timeframe:
Milestone Est. Completion Date Status
Submission of proposal to AltaThera May 2016 Complete
Submission of proposal to PACES March 2016 Complete
Presentation of proposal @ pre-HRS PACES research meeting May 2016 Complete
Presentation of proposal again @ pre-HRS PACES research meeting May 2017  
Creation of online database May 2017 – July 2017  
Creation of individual site IRBs May 2017-October 2017  
Request of individual site grant funding from AltaThera May2017-October 2017  
Patient enrollment June 2017-November 2018  
Abstract submission to HRS 2019 December 2018  
Manuscript preparation Spring 2019  
Manuscript publication Summer 2019  
 
References:
  1. Ho DS, Zecchin RP, Cooper DA, Richards AB, Uther JB, and Ross L.  Rapid intravenous infusion of d-1 sotalol: time to onset of effect on ventricular refractoriness, and safety.  European Heart Journal 1995:16;81-86. 
  2. Ho DS, Zecchin RP, Richards DA, Uther JB, and Ross DL. Double-blind trial of lignocaine versus sotalol for acute termination of spontaneous sustained ventricular tachycardia. Lancet 1994:344;18-23.
  3. Sung R, Tan HL, Karagounis L, Hanyok J, Falk R, Platia E, Das G, Hardy SA and the Sotalol Multicenter Study Group.  Intravenous sotalol for the termination of supraventricular tachycardia and atrial fibrillation and flutter: A multicenter randomized, double-blind, placebo-controlled study.  American Heart Journal 1995:129;739-48.
  4. Neumar RW, Otto CW, Link MS, Kronick SL, Shuster M, Callawa C, Kudenchuk PJ, Ornato JP, McNally B, Silvers SM, Passman RS, White RD, Hess EP, Tang W, Davis D, Sinz E, and Morrison LJ.  AHA/ACC/HRS 2010 Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 8: Adult Advanced Cardiovascular Life Support. Circulation 2010:122l;S729-S767.
  5. Zhang Y, Li X, Xu Z, and Lui H. Efficacy of intravenous sotalol for treatment of incessant tachyarrhythmias in children.  Chinese Journal of Practical Pediatrics 2013:28;4.
  6. Li X, Zhang Y, Liu H, Jiang H, Ge H, and Zhang Y. Efficacy of Intravenous Sotalol for Treatment of Incessant Tachyarrhythmias in Children. American Journal of Cardiology 2017:119;1366-1370.
If you're interested, please submit a request via email for an unrestricted educational grant to support an investigator initiated clinical trial on your institution’s letterhead, to: Lindsey Malloy-Walton at lemalloywalton@cmh.edu. Please title the Subject line of your email: “IV sotalol registry grant request – Name of your Institution

Data Collection Form

Ventricular Pacing in Single Ventricle Congenital Heart Disease—A Multicenter International Study

Introduction
Chronic ventricular pacing has been associated with poor systolic function in a subset of pediatric patients with complete heart block and structurally normal hearts. Ventricular pacing results in dyssynchronous electrical activation and consequently dyssynchronous mechanical activation. The effect of chronic ventricular pacing in congenital heart disease is less well understood, especially in patients with single ventricle physiology. Prior studies of single ventricle patients who have pacemakers have shown conflicting results. We recently showed in a small two center study,  that single ventricle patients who were ventricularly paced > 50% of the time had a 5 fold increase in mortality/transplant (Heart Rhythm 2017).  The purpose of this study is to extend that research, and to identify possible predictors of worse outcome in paced single ventricle patients as part of a multicenter international registry. We also would like to better understand the relationship between mechanical dyssynchrony in this group to pacing site and ventricular morphology, with the ultimate aim of being able to determine optimal multisite pacing in this patient population.

Aims
  1. To assess morbidity and mortality in ventricularly paced single ventricle congenital heart disease (CHD) patients, using a primary endpoint of heart transplantation or death, and the secondary endpoints of moderate-severe ventricular dysfunction and atrioventricular valvar regurgitation (AVVR), as compared to age, gender and type of single ventricle matched controls.
  2. To determine the patient characteristics that predispose a single ventricle CHD patient requiring ventricular pacing to a higher risk of heart transplantation or death, and the development of moderate-severe ventricular dysfunction and AVVR.
  3. To determine the association of mechanical dyssynchrony indices to pacing lead location in a subset of ventricularly paced Fontan patients, as compared to age, gender and type of single ventricle matched controls.
Research Design and Methods
We propose two parts to this study: a multicenter retrospective cohort study to further evaluate the risk of pacing in single ventricle patients, as well as a cross-sectional study to assess the association of mechanical dyssynchrony indices to pacing site and outcomes. Patients will be retrospectively identified from collaborating centers.
  • Inclusion criteria: single ventricle CHD patients between ages 1 month and 30 years with dual chamber epicardial pacemaker placement (paced group) from 2000 to present
  • Exclusion criteria: single ventricle CHD patients without echo prior to pacemaker placement, or those without 2-view CXR and EKG to confirm pacemaker lead placement
  • Control group:  single ventricle CHD patients between ages 1 month and 30 years from the same institution who are age, gender, and single ventricle morphology (RV vs LV) matched in a 2:1 ratio with similar follow-up periods from the same time period
  • Outcomes:
    • Primary outcome is heart transplantation or death
    • Secondary outcome is development of moderate-severe ventricular dysfunction or AVVR
  • Clinical and echo parameters will be compared at baseline, defined as pre-pacing in pacing group and at similar ages in controls, as well as every 6 months from pre-pacer data until last clinical follow-up
  • Data to be collected:
    • Patient characteristics: age, gender, weight, anatomy, surgical history, type of AV nodal disease, location of pacemaker leads, percentage of time V pacing, QRS duration, NYHA class, disposition
    • Echo data: qualitative and quantitative ventricular function, qualitative AVVR, qualitative assessment of AI/AS
  • Cross-sectional study of 10 paced Fontan patients with single RV morphology and 10 paced Fontan patients with single LV morphology who are paced >50% of time compared to age, gender and type of single ventricle controls in a 1:1 ratio .  All patients will receive an echocardiogram specifically measuring tissue Doppler indices of mechanical dyssynchrony and function (see attached protocol).
For further information please contact Anne Dubin : amdubin@stanford.edu

Fetal Diagnosis of long QT syndrome

Specific Aims: Long QT syndrome (LQTS) is an inherited channelopathy. Although considered to be rare in children, LQTS is 3 times more common than childhood leukemia. LQTS may cause syncope, cardiac arrest or sudden death as a result of life-threatening ventricular arrhythmias at any age, from fetal to adult life. In fact, LQTS is the leading cause of sudden arrhythmic death in people <35 years of age and is often diagnosed only after cardiac arrest.  LQTS diagnosis before symptoms is important because primary prevention is extremely effective in preventing LQTS associated life-threatening ventricular arrhythmias. Ideally, LQTS would be diagnosed before birth and primary prevention initiated during infancy. Unfortunately, the fetal diagnosis of LQTS is challenging due to lack of a suitable method to distinguish normal fetuses from those with LQTS. The objective of this study is to address this problem by defining an algorithm to discriminate fetuses with LQTS from those who do not have LQTS.

The postnatal diagnosis of LQTS is suggested by a prolonged QT interval on 12 lead ECG, strengthened by a positive family history and/or characteristic arrhythmias and confirmed by genetic testing. However, for several reasons such LQTS testing cannot be performed successfully before birth. First, fetal ECG is not possible and direct measure of the fetal QT interval by magnetocardiography is limited to fewer than 10 sites world-wide. Second, while genetic testing can be performed in utero, there is risk to the pregnancy and the fetus. Third, although some fetuses present with arrhythmias easily recognized as LQTS (torsade des pointes (TdP) and/or 2° atrioventricular (AV) block), this is uncommon, occurring in <25% of fetal LQTS cases. Rather, the most common presentation of fetal LQTS is sinus bradycardia, a subtle rhythm disturbance that often is unappreciated to be abnormal. Consequently, the majority of LQTS cases are unsuspected and undiagnosed during fetal life, with dire consequences. For example, maternal medications commonly used during pregnancy can prolong the fetal QT interval and may provoke lethal fetal ventricular arrhythmias. But the most significant consequence is the missed opportunity for primary prevention of life threatening ventricular arrhythmias after birth because the infant is not suspected to have LQTS before birth. The over-arching goal of our study is to overcome the barriers to prenatal detection of LQTS. We plan to do so by developing an algorithm using fetal heart rate (FHR) which will discriminate fetuses with or without LQTS.

Immediate Goal: We propose a multicenter pre-birth observational cohort study to develop an FHR/gestational age (GA) algorithm from a cohort of fetuses recruited from 13 national and international centers where one parent is known by prior genetic testing to have a mutation in one of the common LQTS genes (KCNQ1, KCNH2 or SCN5A). We have chosen this population because 1.) these mutations are the most common genetic causes of LQTS, and 2.) offspring will have high risk of LQTS as inheritance of these LQTS gene mutations is autosomal dominant. Thus, progeny of parents with a known mutation are at high (50%) risk of having the same parental LQTS mutation. The algorithm will be developed using FHR measured serially throughout pregnancy. All offspring will undergo postnatal genetic testing for the parental mutation as the gold standard for diagnosing the presence or absence of LQTS.

For more information, please download the study protocal and/or contact Bettina Cuneo at Bettina.Cuneo@childrenscolorado.org.


Heart Sounds study for detection of emergent complete AV block

Specific Aims:  Fetal complete AV block (CAVB) is associated with high morbidity and mortality. The most common cause of CAVB is injury to the conduction system secondary to maternal anti-SSA (Sjogren) antibodies. These antibodies cross the placenta at ~ 18 weeks of gestation and cause inflammation and fibrosis of the fetal AV node, usually by 26 weeks gestation (1). The disease burden of CAVB is considerable (2, 3). For example, the 35% of affecteds who die is a much higher mortality than the 11% cited for all congenital anomalies together. If the CAVB fetus survives to birth, almost all require life-long cardiac pacing. Furthermore, in addition to perinatal morbidity and mortality, individuals with CAVB are subjected to complications associated with long-term cardiac pacing (4, 5).

CAVB develops in ~4% of anti-SSA antibody + pregnancies. CAVB risk is greater if a previous offspring had CAVB (recurrence is ~20%), and if maternal anti-SSA antibody levels are > 100 U/ml (CAVB event rate 57%) (6). CAVB is irreversible, resulting in either fetal demise or life-long pacemaker dependence.  Clinical evidence suggests there is a ~ 24 hour period when an irregular fetal heart rhythm (FHR) signals the emergence of CAVB as the rhythm transitions from normal to CAVB. This transition period is referred to as “emergent” CAVB (eCAVB). Identification of eCAVB is critically important because anti-inflammatory treatment during this period has been reported to restore sinus rhythm (3, 6-11).  However, reports of successful treatments are only anecdotal because standard surveillance of anti-SSA + pregnancies by weekly fetal echo fails to detect eCAVB since eCAVB develops in ~24 hours. Thus, most cases of CAVB are detected after the fact and after the time when treatment can be ineffective.  An important barrier to progress in this field is lack of a FHR surveillance method to detect eCAVB. A dependable method to detect eCAVB would allow design of studies to test efficacy of therapy to prevent progression to irreversible CAVB.  Continuous FHR surveillance would be the true “gold standard” to detect eCAVB, but this is not feasible.
To overcome this barrier to progress, we propose that pregnant anti-SSA antibody + mothers use a commercially available Doppler FHR monitor at home 2x/day to detect the irregular FHR of eCAVB. Since eCAVB develops in ~ 24 hrs, 2x/day monitoring will provide 2 opportunities to detect eCAVB. We previously demonstrated that anti-SSA antibody + mothers can detect eCAVB using the FHR monitor at home (11). In a multicenter recruitment of 140 mothers, we found that 94% of eligible subjects enrolled and 96% completed monitoring with a false positive rate < 2%. No eCAVB went undetected (12). Together, these findings demonstrate 1) home-based FHR monitoring is feasible, 2) mothers can recognize irregular FHR in the ambulatory setting and 3) eCAVB can be detected by this technique. The over-arching goal of this study is to build on our preliminary results and compare the specificity/sensitivity of eCAVB detection between 2 methods of FHR surveillance: 2x/day home FHR monitoring (home monitoring) and the current standard of care, weekly FHR monitoring by echocardiography (office monitoring). We propose a multicenter clinical observational trial of anti-SSA + pregnancies in which the 2 interventions will be compared to determine which intervention is more successful in detecting eCAVB. We propose 2 specific aims.

  • Specific Aim 1:  To compare the success of detection and the sensitivity/specificity for identifying eCAVB between home monitoring versus office monitoring. We hypothesize that eCAVB will be more frequently detected by 2x/day home monitoring than by standard office monitoring. To test this hypothesis, we will compare the detection (diagnostic rate), and the sensitivity/specificity for identifying eCAVB between the two surveillance techniques (interventions).  Each mother will serve as her own control as both interventions will be performed in each mother. Assuming 4/100 fetuses will develop eCAVB, a sample size of 500 mothers will provide ~90% power at 5% significance to show that 2x/day maternal ambulatory FHR monitoring will more frequently detect eCAVB than fetal echo surveillance.
  • Specific Aim 2:  To risk stratify development of fetal eCAVB by maternal anti-SSA antibody levels. We hypothesize that since maternal anti-SSA antibodies levels are higher in fetuses who develop CAVB, levels will be higher in fetuses that develop eCAVB. If so, maternal anti-SSA levels can be used in the future to risk stratify anti-SSA positive pregnancies allowing for personalized surveillance. To test this hypothesis we will analyze the strength of the association with maternal antibody levels and the development of fetal eCAVB using ROC from logistic regression. With a sample size of 500 subjects (Aim 1), there will be 80% power at 5% significance to show C-statistics > 0.8 if the true C-statistic is 0.95.

For more information, please download the study protocal and/or contact Bettina Cuneo at Bettina.Cuneo@childrenscolorado.org.


Multi -Center Research Project Query

   Jen Maldonado (Lampe) BS, RT(R), CVI (Research Coordinator for Pediatric Cardiology)
   Ian H. Law, M.D. (Stead Family Department of Pediatrics, University of Iowa Children’s Hospital, University of Iowa Carver   
      College of Medicine)

We at University of Iowa Stead Family Children’s Hospital have completed a background study evaluating atrial antitachycardia devices in patients who have congenital heart disease. Preliminary results have shown a reduction in atrial arrhythmia burden manifest by a significant decrease in DC cardioversion. We are currently in discussion with Medtronic (currently the only atrial ATP device manufacturer) and are hoping to secure funding for a multi-center prospective and retrospective study (AntiTachycardia PAcing in The Congenital Heart population) to evaluate overall efficacy and safety of atrial anti-tachycardia devices in congenital heart disease.
 
Inclusion: Any patient with CHD that has an implanted pacemaker or ICD with atrial anti-tachycardia pacing therapy
 
Exclusions: Patients with CPVT, HCM, LQT, ARVC, Brugada
 
Study design: Retrospective review of charts to gather previously implanted patients and follow. We will consent new placement for the next 3 years then follow all subjects for an additional 5 years.
 
There are a few things that would be great to have you help us with:

  1.  Would you be potentially interested in participating?
  2. How many patients do you currently follow who have atrial anti-tachycardia devices and congenital heart disease?
  3. Approximately how many atrial anti-tachycardia devices do implant per year?
If you are interested please contact Jennifer-lampe@uiowa.edu.
We will let you all know once we have secured funding and are ready to get things going.

Intravenous Sotalol in Pediatric and Congenital Patients:  A Multi-center Registry

   Lindsey Malloy-Walton (Children's Mercy Kansas City)
   Jennifer Silva (St. Louis Children's Hospital) and
   Phil Saul (West Virginia University)

Background:
Though intravenous sotalol has been used outside the US for over thirty years, it was only recently approved by the Food and Drug Administration (FDA; 2009) and reintroduced to the US market (2015).  Sotalol is a class III antiarrhythmic agent that prolongs action potential duration while also blocking beta-adrenergic receptors.  Intravenous (IV) sotalol has been used for many different types of tachyarrhythmias with the distinct advantage of having an oral equivalent with more tolerable side effects.  This is of particular importance in pediatric patients as well as young adults with congenital heart disease who will likely remain on antiarrhythmic therapy for long periods of time (potentially a lifetime).  Additionally, collateral damage to developing organ systems by other class III antiarrhythmics makes sotalol an important alternative in this population. 

Currently, IV sotalol is indicated for substitution of oral sotalol in patients who are unable to take oral medications per the FDA.  Infusion options are based on the current adult literature, FDA guidance, and modeling with reported infusion times between one and thirty minutes, most commonly five minutes1,2.  Typical IV sotalol doses have been reported around 1-1.5mg/kg/dose3.  However, pediatric dosing for IV sotalol has not been well studied, with a single case series from Zhang4 et al using IV sotalol in children with normal left ventricular function.   

The purpose of this study is to evaluate the safety and efficacy of IV sotalol being given for tachyarrhythmias to pediatric patients as well as adults with congenital heart disease.  Our goal is to collect approximately 100 patients from 10 centers over an 18 month time period. To facilitate this, a multicenter prospective nonrandomized registry study will be performed to address specific aims.

If you are interested in this study, please see the Registry Proposal and Data Collection Form; contact Lindsey Malloy-Walton at lemalloywalton@cmh.edu for more information.


Time course of sinus node function recovery in patients with sinus node dysfunction noted immediately after congenital heart surgery.

   Seshadri Balaji MBBS; FRCP(UK); PhD;
   Department of pediatrics,
   Oregon Health & Science University, Portland OR.

Sinus node dysfunction (SND) may be an immediate complication of certain forms of surgery for congenital heart defects in children and young adults such as the Fontan operation. We currently have no idea when or whether the sinus node of a particular patient is capable of recovery if damaged at surgery. Knowing the answer will help us solve the problem we have at present of either placing unnecessary pacemakers in too many children who subsequently recover sinus node function or else waiting with temporary pacing for prolonged periods of time hoping the sinus node will recover. An interesting parallel to SND is the issue of post-surgical complete heart block due to damage to the atrio-ventricular node. A landmark study by Weindling et al in 1998 showed that AV node function was unlikely to occur beyond 10 days after surgery. This study led to the current practice of waiting for 7-10 days and placing a permanent pacemaker if recovery has not been seen within that time. This proposed study will aim to answer the question: how long should one wait before placement of a permanent pacemaker for SND? Or put another way, what is a reasonable time frame within which sinus node recovery can be expected in patients where it presumably has not been irretrievably damaged? Statistical power estimates suggest the need to study 34-40 patients with SND. So, this study will be an official PACES prospective multi-center prospective data collection.

If you are interested in this study, please see the full protocol for this study and contact Dr. Balaji at (balajis@ohsu.edu).


Defibrillation Testing at the Time of Cardioverter Defibrillator Implantation in Pediatric and Congenital Heart Disease Patients

   Dr. Carolina Escudero, Dr. Elizabeth Stephenson

The role of defibrillation testing in children and patients with CHD has not been widely studied and its utility is unclear. We are performing a retrospective, multicenter cohort study investigating defibrillation testing at the time of ICD implantation between 2000-2015. This primary objective of this study is to determine the yield of defibrillation testing in the pediatric and CHD population and the frequency of ICD system or programming changes as a result of defibrillation testing. We also aim to determine which pediatric and CHD patients are at higher risk for failed defibrillation testing, as well as to determine the trends and proportions of pediatric and CHD patients who are receiving defibrillation testing at the time of ICD implantation. We are seeking participating centers with an enrollment goal of ~400 patients.

For further information, please contact: carolina.a.escudero@gmail.com
 


Sudden Death in Wolff-Parkinson-White Syndrome

   Susan Etheridge, MD

In order to better protect those at risk of sudden death in Wolff-Parkinson-White (WPW), a prospective database is being established based on a retrospective collection of WPW patients with or without life threatening events (LTE). In addition to patients that were included in the retrospective arm of the study, young patients (from birth to age 21) will be enrolled and detailed information including demographic and clinical characteristics, electrophysiological, info surrounding LTE and interventions will be entered into a WPW database using REDCap. This will allow for comparison of WPW patients with and without LTE, identifying risk factors and the effectiveness of interventions. The investigators are currently seeking international centers to enroll patients. Approximately $1000 will be available to support study coordinators at the first 15 centers that enroll patients.

Further Information: susan.etheridge@hsc.utah.edu
 


CPVT Prospective Registry

   Shubhayan Sanatani, MD

Current gaps exist in the risk and management of patients with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). Support has been received from the Heart and Stroke Foundation of Canada to fund a multi-center, prospective registry of all pediatric CPVT patients and their first degree relatives. Patient data including demographics, diagnostic tests, clinical events and family history will be entered into a REDCap database at participating sites. Probands and affected family members will be assessed at baseline and yearly, whereas unaffected family members will be assessed once over the study period. This study is seen as a collaboration and ideas for sub-studies are welcome. The aim is to have 10 sites enrolling patients by the end of the 2015 calendar year and a total of 15-20 sites over the next 12 months. Participating sites will receive a nominal fund for site start-up costs and for patient recruitment. For sites wishing to enroll patients into the study, please contact the Coordinating Site Research coordinator for assistance with obtaining local IRB approval and study information.

Further Information: Sonia.Franciosi@cw.bc.ca
 


Solar SVT

   Carolina Escudero, MD
Knowledge of the management of acute SVT in infants is currently limited. A group of investigators is conducting a prospective, multi-center, observational cohort study in order to determine the most effective second-line therapies for acute SVT termination in infants when vagal maneuvers and adenosine fail. A secondary objective is to determine the most effective medications for continued control of SVT after discharge from the hospital. Patients that are less than one year with AVRT or AVNRT and receiving a pharmacological agent in addition to adenosine and/or vagal maneuvers will be included in the study. Data including demographics, medical history, acute treatment for SVT, discharge information and one year follow up after SVT presentation will be entered into a REDCap database. The investigators are currently seeking centers to enroll patients. The enrollment goal is at least 120 patients over 2 years from 10 centers (average of 6 patients per site).

Further Information: carolina.a.escudero@gmail.com, tony.mccanta@gmail.com or ssanatani@cw.bc.ca.
 


Riata Lead Failure in Pediatric and Congenital Heart Disease Patients

   Carolina Escudero, MD
Conductor coil externalization (CCE) is a more common lead failure compared to electrical failure of ICDs in adults. Currently, the rate of Riata lead structural or electrical failure in pediatric or CHD patients is unknown. This is a multi-center, retrospective cohort study to determine the rate of CCE failure, electrical failure and the correlation between both failures in pediatric and CHD patients. Data including patient demographics, cardiac structural diagnosis or surgery as well as primary versus secondary prevention from patients with a transvenous Riata or Riata ST lead implantation who are less than 18 years old or patients with congenital structural or congenital heart disease will be entered into REDCap. The investigators are currently seeking participating centers and plan to enroll 56-60 patients by the end of the year. The overall goal of the study is to improve patient outcomes in patients with Riata or Riata ST leads in place. Future studies may include testing Durata leads and similar patient outcomes.

Further Information: joseph.atallah@albertahealthservices.ca or carolina.a.escudero@gmail.com
 


LQTS Novel Gene Discovery Program

   Michael Ackerman, MD
With the use of genetic testing, emerging technologies and a large LQTS patient cohort, over 17 genes have been implicated in LQTS including CAV3, SCN4, AKAP9 and SNTA1 and more recently, CACNA1C, CALM3 and TRDN. Approximately 20% of LQTS patients remain genetically elusive. In order to elucidate further genes that could lead to LQTS, more gene negative individuals with a robust LQTS phenotype are needed. Local IRB approval is not required, rather, patients can be referred directly to the coordinating study site through facilitated enrollment. Currently, this study is well funded and the investigators are seeking more collaborating clinicians with robust LQTS phenotype positive patients.

Further Information: Carla Haglund (507) 284-8900 or ackerman.michael@mayo.edu.
 


Exercise in Genetic Cardiovascular Disease (LIVE-LQTS and LIVE-HCM)

   Michael Ackerman, MD
The effect of lifestyle and exercise on LQTS patients and patients with HCM will be investigated in this NIH funded study. Patients with LQTS or HCM aged 8-50 years, with or without an ICD at any level of exercise are included in this study and equipped with a FitBit. Overall aims are to determine the incidence of arrhythmic events over 3 years and quality of life in sedentary vs moderate/vigorous exercisers. Currently, 30 active centers are involved in the study. Patients may be referred directly to the coordinating center and enrolled through facilitated enrollment. All questionnaires and interviews are carried out remotely over the phone so there are no geographic constraints limiting patients from enrolling. The goal is to enroll a total of 4000 patients; approximately 2000 with LQTS and 2000 with HCM.

Further Information: (866) 207-9813 or email [live.hcm@yale.edu or live.lqts@yale.edu]
(PI’s: Drs. Lampert, Ackerman and Day).
 


HCM and Risk Stratification for Sudden Death

   Maully Shah, MD
This is a retrospective, multi-center chart review to determine whether risk factors related to clinical history, family history, ECG, echocardiographic, MRI, genetic testing and/or exercise predict sudden cardiac death. This study includes patients less than 20 years of age with HCM, with or without an ICD. Currently, 26 centers are participating in the study and another 20 centers have expressed interest. The goal is to have completed data collection by the end of the year. This study is funded by Medtronic and each participating site is reimbursed $2000.

Further Information: Research coordinator Veronica O’Connor [OConnorV@email.chop.edu]
 


Timothy Syndrome in the Contemporary Era (Long QT Syndrome Type 8)

   Maully Shah, MD
The primary objective of this study is to determine the mortality rate and average life span of children diagnosed with Timothy Syndrome (TS) in the current era (2000-2013). Other objectives include determining ECG features, mutations and treatments for patients with TS. Data will be entered into REDCap. Currently, 10 US centers have expressed interest. However, the investigators would like to include all patients with TS and therefore, seek participation from local, national and international centers.

Further Information: Research coordinator Veronica O’Connor [OConnorV@email.chop.edu]
 


PVC-Induced Cardiomyopathy in Children

   Maully Shah
Frequent PVCs results in left ventricular dilatation as well as reversible cardiomyopathy in adults.  However, the impact of frequent PVCs in children is unknown. The goal of this retrospective, chart review study is to determine the type and impact of increased PVC burden on left ventricular function in pediatric patients without structural heart disease. An extensive review of medical charts, echocardiograms, Holter, ECG and stress tests will be performed. Currently, IRB approval has been obtained for this multi-center study although no funding is in place. Ideas for funding include contributions from PACES members or seeking funding from local foundations such as the Children’s Heart Foundation.
 


Congenital Heart Block International Research Network

   Robert Hamilton, MD
The aims of this CHB international network are many and include: establishing a network of CHB collaborators, establish guidelines and protocols for monitoring/treatment of CHB as well as for data sample collection, a registry and biobank, a CIRN website and organizing a CHB international meeting or workshop. To date, funding is in place, IRB approval has been obtained, registry and biobank are established and a CIRN website has been developed. The investigators are seeking participation from additional centers. Future goals are to establish a pediatric ARVC registry and promote gene discovery for ARVC and other arrhythmia syndromes.

Further Information: robert.hamilton@sickkids.ca
 


Supporting Hemodynamics during Ventricular Tachycardia Ablation using the Impella Transcatheter System: “The SHVITS Trial”

   Steve Fishberger
Ablation of patients with ventricular tachycardia is difficult and leads to poor outcomes. Mapping ventricular tachycardia with ablation leads to better long term outcomes as compared to substrate ablation. The Impella Device, a catheter based miniaturized rotary blood flow pump, which has been used primarily in adults, may also be useful in pediatric patients with structural heart disease and cardiomyopathy where mapping of VT is impeded due to hemodynamic instability. This is a multi-center, prospective study where patients 10 years or older, greater than 50 kgs with documented ventricular tachycardia are included. The investigators are seeking centers to participate in this study in order to determine the value of this device in patients with ventricular tachycardia. The goal is to stabilize patients with ventricular tachycardia and improve patient treatment outcomes.
 


AVNRT in CHD

   John Papagiannis
The relationship of AVNRT in CHD is unknown. The investigators have started to enroll CHD patients with a diagnosis of AVNRT and are seeking participation from local, national and international centers. The goal is to have 20-25 centers participate, each enrolling 4-5 patients for a total enrollment of 100 patients. Results from this study will address current gaps in our understanding of AVNRT in CHD.

Further Information: jpapagiannis@cmh.edu.