Cardiology

Research Activities

Pediatric Heart Network
The Division is one of eight clinical research centers for the Pediatric Heart Research Network (PHN), an important NIH-sponsored multi-center network with the overall goal of evaluating new and existing treatments and management approaches for children with structural congenital heart disease, inflammatory heart disease, heart muscle disease, and arrhythmias.

The major ongoing projects of the PHN include the following:

• Marfan Trial -- a randomized trial of beta blocker therapy (atenolol) vs. angiotensin II receptor blocker therapy (losartan) in individuals with Marfan syndrome. The primary outcome is rate of change in aortic root (sinuses of Valsalva) size, as measured by body surface area-adjusted Z-score. Contact: Wyman W. Lai, MD, MPH
• Single Ventricle Reconstruction -- a Phase III, randomized trial of the RV-to-PA shunt vs. modified Blalock-Taussig shunt of patients with hypoplastic left heart syndrome undergoing a Norwood procedure. Pre- and post-operative data, neurodevelopment and genetic evaluation information is collected and subjects are followed until 14 months of age. The primary endpoint is death or cardiac transplantation at 12 months of age. An extension of this study has been approved to follow subjects through 6 years post-randomization, with data collected annually between ages 2 and 6 years, as well as before and after the Fontan surgery. Contact: Ismee Williams, MD, MS
• Trial of ACE Inhibition in Infants with Single Ventricle -- a Phase III, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of administering ACE-I to infants with single ventricle physiology. Data is collected to determine the effect of ACE inhibition on ventricular function and remodeling and patients are followed until 14 months of age. The primary endpoint is weight-for-age Z-score at 14 months of age. Contact: Karen Altmann, MD
• Ventricular Volume Variability Study -- an observational study of children with dilated cardiomyopathy to compare longitudinal data concerning indices of ventricular function and intra- and inter-observer variability. The primary endpoint is inter-study variability of echocardiographic variables; variance at a single point in time and variance of change over time. Contact: Karen Altmann, MD
• Fontan Study -- a cross-sectional study to determine the interrelationships between health status and measures of cardiac performance in children with congenital heart disease who have undergone a Fontan procedure as surgical palliation for functional single ventricle. The primary aim of this study is to determine the relationship between a) laboratory measures of exercise capacity and systemic ventricular function, and b) indices of overall health and functional status in Fontan patients 6 to 18 years of age. Laboratory measures include exercise capacity, MRI assessment, echocardiographic assessment, and biochemical assessment. Contact: Welton Gersony, MD

Pulmonary Hypertension
The Pulmonary Hypertension Center is currently participating in several multicenter national and international clinical trials of novel therapeutics for the treatment of pulmonary arterial hypertension, as well as genetic and pharmacogenetic studies to further understand mechanisms of disease and differences in clinical phenotypes of patients with pulmonary hypertension.

• Ambrisentan Pharmacokinetic trial in Children -- a clinical trial designed to assess the pharmaocokinetic properties of ambrisentan (a selective endothelin receptor antagonist) in children with pulmonary arterial hypertension. This medication has been previously approved in adults with pulmonary arterial hypertension, but little is known about its safety and dosing in children. Contact: Erika Berman Rosenzweig, MD
• Ambrisentan in Eisenmenger Syndrome Trial -- a multicenter trial being conducted to evaluate the safety and efficacy of the endothelin receptor antagonist ambrisentan for symptomatic patients with pulmonary hypertension due to the Eisenmenger syndrome. Contact: Erika Berman Rosenzweig, MD
• The REVEAL Registry -- The Pulmonary Hypertension Center is participating in a national registry of patients with various forms of pulmonary arterial hypertension. The registry currently has over 3,400 patients enrolled with the intent of capturing important data to further our understanding of disease and treatment patterns of pulmonary arterial hypertension. Contact: Erika Berman Rosenzweig, MD
• Griphon Study -- an international study of a novel oral prostacyclin receptor agonist for the treatment of symptomatic pulmonary arterial hypertension. Contact: Erika Berman Rosenzweig, MD
• Cicletanine -- a multicenter clinical trial to investigate the use of oral cicletanine for the treatment of adults with symptomatic pulmonary arterial hypertension. Contact: Erika Berman Rosenzweig, MD
• Oral Remodulin -- a multicenter study that will investigate the use of an oral prostanoid, remodulin in patients with symptomatic pulmonary arterial hypertension. Contact: Erika Berman Rosenzweig, MD
• Inhaled Treprostinil Pharmacokinetic Study -- a multicenter trial to determine the pharmacokinetic properties of inhaled treprostinil in patients with pulmonary arterial hypertension on chronic inhaled treprostinil. Contact: Erika Berman Rosenzweig, MD
• Seraphin Trial -- an international study designed to evaluate the safety and efficacy of a novel tissue targeted endothelin receptor antagonist in patients with pulmonary arterial hypertension. Contact: Erika Berman Rosenzweig, MD
• Iloprost in Neonates -- a study to evaluate the safety and efficacy of iloprost, an inhaled prostanoid in neonates suffering from persistent pulmonary hypertension of the newborn. Contact: Erika Berman Rosenzweig, MD
• Dhreams Study -- a multicenter NIH funded study to develop a better understanding of the molecular genetic basis of congenital diaphragmatic hernia (CDH), which is a cause of pulmonary hypertension. The study is designed to identify specific alterations in genes that contribute to CDH through genetic analysis of biological samples from children with CDH and their family members. Contact: Erika Berman Rosenzweig, MD or Wendy Chung, MD, PhD, or visit: www.cdhgenetics.com

Non-invasive Imaging Laboratory
The Non-invasive Imaging Laboratory is involved in multiple protocols focused on the evaluation of ventricular function in children with heart disease by echocardiography and cardiac magnetic resonance imaging. It is also integrally involved in other protocols in the Division that require the precise diagnosis and non-invasive evaluation of cardiovascular anomalies in fetuses and children.

• Tricuspid Annular Plane Systolic Excursion (TAPSE) in Pediatric Pulmonary Hypertension -- a retrospective study of images from clinical echocardiographic examinations. In the initial stage of the study, measurements of TAPSE by M-mode and two-dimensional echocardiography methods will be compared. Subsequently, TAPSE information will be compared to clinical information obtained from the medical chart on patients with pulmonary hypertension. Contact: Wyman W. Lai, MD, MPH
• Ventricular Dyssynchrony in Pediatric Heart Disease -- a retrospective study of all infants and children with congenital or acquired heart disease. The primary goal is to determine whether mechanical cardiac dyssynchrony is present in congenital or acquired heart disease as demonstrated on echocardiography. Contact: Marc Richmond, MD
• Echocardiographic assessment of right ventricular structure and function -- a proposed study to evaluate the ability of newer echocardiographic methods to determine right ventricular size and function and pulmonary vascular hemodynamics compared to those values obtained by cardiac MRI and right heart catheterization. Contact: Wyman W. Lai, MD, MPH
• Baseline Correction of Phase Contrast Images in Congenital Cardiac Magnetic Resonance Imaging -- a retrospective study of the impact of using phantom correction on phase contrast images performed on clinical CMR examinations. The differences considered clinically significant include a change in pulmonary or aortic flow, pulmonary-to-systemic flow ratio, valvular regurgitation, and right/left lung flow. Contact: Wyman W. Lai, MD, MPH

Fetal Cardiology

• Doppler Ultrasound Evaluation of Hydrops Fetalis in Congenital Heart Disease -- a retrospective study of ultrasounds of fetuses referred for fetal echocardiogram to evaluate the association between hydrops fetalis and abnormal systemic venous Doppler patterns. Contact: Ismee Williams, MD, MS
• Fetal Tetralogy of Fallot -- a study to examine the impact of extracardiac anomalies and chromosomal abnormalities on the perinatal outcome of fetuses affected by tetralogy of Fallot. Contact: Julie Glickstein, MD
• Fetal Transposition of the Great Arteries- a retrospective study that investigates the influence of delivery planning on the neonatal outcome of patients with transposition of the great arteries. Contact: Stephanie Levasseur, MD
• Fetal Electrocardiographic Monitoring -- a prospective study that aims to evaluate whether monitoring a fetal electrocardiographic signal (fECG) is useful to diagnose and treat fetal arrhythmias. Contact: Ismee Williams, MD, MS
• Fetal Predictors of Neurodevelopmental Outcome -- a prospective study that aims to investigate fetal characteristics such as autonomic nervous system development and fetal brain blood flow, which may be useful for predicting ultimate neurodevelopmental outcomes—such as developmental delay and behavioral problems—in children with congenital heart disease. Contact: Ismee Williams, MD, MS
• Impact of Fetal Echocardiography on Maternal Anxiety -- an investigation of how referral for fetal echocardiography affects maternal anxiety levels both before and after the echocardiogram. Contact: Ismee Williams, MD, MS
• Early Fetal Echocardiography -- a study that evaluates the impact of early fetal echocardiography (around 13 weeks of pregnancy). Contact: Ismee Williams, MD, MS
• Parent Understanding of Congenital Heart Disease -- a study that investigates how fetal cardiac diagnosis improves parental understanding of their child's heart defect. Contact: Ismee Williams, MD, MS
• Cardiac Effects of Twin-Twin Transfusion Syndrome -- a prospective study that monitors the cardiovascular changes seen in Twin-Twin Transfusion Syndrome (TTTS) both before and after laser therapy. Contact: Stephanie Levasseur, MD

Heart Failure and Cardiac Transplantation

• Pediatric Heart Transplant Data Registry -- a prospective multicenter data registry with 23 participating centers of all patients less than 18 years old who are listed for cardiac transplantation with UNOS through our institution. Contact: Linda J. Addonizio, MD
• Genetic Contributions to Graft and Patient Outcomes -- a NIH-funded multicenter study at six large North American pediatric transplant centers. This study addresses how three genetically determined variables -- HLA incompatibility, mediators of inflammation, and immunosuppressive drug efficacy -- influence cardiac transplantation outcome in pediatric patients. Contact: Linda J. Addonizio, MD
• Pediatric Cardiomyopathy Registry Cohort Study Protocol -- a prospective cohort study followed at up to 15 clinical centers in the United States. This study aims to collect clinical and echocardiographic data on the course and outcomes of cardiomyopathy in a cohort of children; and to establish the longitudinal course of functional status in children with cardiomyopathy, and analyze the relationship to clinical events and outcomes. Contact: Linda J. Addonizio, MD
• Alloantibodies in Cardiac Transplantation -- a NIH-funded multicenter study (CTOTC) with the primary objective to determine the clinical outcomes of sensitized pediatric heart transplant recipients with a positive donor-specific cytotoxicity cross-match and to compare them with outcomes in non-sensitized participants. Contact: Linda J. Addonizio, MD
• Interagency Registry of Mechanically Assisted Circulatory Support -- a national, prospective registry of hospitals implanting durable mechanical support devices that will contain clinical and follow-up data, including death, explant, rehospitalization, and three adverse advents: neurological dysfunction, infection, and device malformation. Contact: Jonathen Chen, MD
• Quality of Life Assessment in the Pediatric Cardiac Population -- a multicenter study in the United States and England to test the scores generated by the Pediatric Cardiac Quality of Life Inventory (PCQLI) in children and adolescents with acquired and congenital heart disease. Contact: Marc Richmond, MD
• Pediatric Cardiomyopathy Biologic Specimen Repository -- a study at up to 15 selected Pediatric Cardiomyopathy Registry (PCMR) clinical centers to collect samples from children with cardiomyopathy who are participating in some aspect of PCMR research. In the future, these samples will be available to investigators who propose studies requiring use of biologic specimens that are approved by a repository access committee. Contact: Linda J. Addonizio, MD
• Evaluating the Usefulness of Cardiac PET Imaging in Detecting Coronary Vasculopathy in Pediatric Heart Transplant Patients -- a pilot study to evaluate 13N-NH3 cardiac PET imaging to evaluate coronary flow reserve and prevalence of microvascular disease in pediatric cardiac transplant patients with and without coronary vasculopathy. Contact: Rakesh Singh, MD
• Size-Matching for Pediatric Cardiac Transplantation -- a retrospective review to determine the usefulness of donor characteristics, including bodyweight, as criteria for size matching. A secondary study will be performed to the normal range for the distance between the right atrium-superior vena cava junction to the right atrium-inferior vena cava junction. The potential benefit is the ability to more appropriately size-match donors for heart transplants to recipients. Contacts: Jonathen Chen, MD and Marc Richmond, MD
• Red Blood Cell Distribution Width as a Predictor of Outcomes in Pediatric Heart Failure -- a retrospective review of patients younger than 25 years old with clinical heart failure or pulmonary hypertension to determine whether the presence of anemia and/or an elevated RDW may be useful in predicting adverse outcomes. Contact: Linda J. Addonizio, MD
• Outcomes of Surgical Treatment for Hypertrophic Obstructive Cardiomyopathy -- a retrospective chart review of pediatric patients with hypertrophic obstructive cardiomyopathy who underwent left ventricular septal myomectomy and/or mitral valve replacement. Contact: Linda J. Addonizio, MD
• Impact of Immunosuppressive Therapy and EBV Status on Risk of Post Transplant Lymphoproliferative Disease -- a two-center (Children's Hospital of New York Presbyterian and the Royal Children's Hospital in Melbourne, Australia) retrospective chart review of pediatric patients who underwent heart transplantation to examine the impact of type of immunosuppression therapy and donor and recipient EBV status in relation to risk of subsequent PTLD. Contact: Linda J. Addonizio, MD
• BNP and Pediatric Heart Failure -- a post-hoc analysis of data from the "Multicenter, placebo-controlled, 8-month study of the effect of twice daily carvedilol in children with congestive heart failure due to systemic ventricular systolic dysfunction." The goal of this study is to determine whether BNP increases with increasing clinical severity of heart failure. Contact: Linda J. Addonizio, MD
• Predictors of Outcome in Ventricular Non-Compaction -- a retrospective review of all patients identified with non-compaction of the myocardium at the Children's Hospital of New York Presbyterian. The primary outcome measures are overall survival and transplant-free survival time from diagnosis. Contact: Marc Richmond, MD
• Hepatitis C Virus Infection in Heart Transplant Recipients -- a retrospective study to characterize the effect of HCV infection on both mortality and the incidence of post-transplant complications in children. Contact: Linda J. Addonizio, MD
• Risk Factors in Pediatric Cardiac Transplantation -- a retrospective review of all patients who underwent heart transplantation at the Children's Hospital of New York Presbyterian to determine risk factors for mortality and graft loss. Contact: Linda J. Addonizio, MD

Catheterization Laboratory
The cardiac catheterization laboratory participates in multiple multicenter trials that involve the development and assessment of new transcatheter devices and transcatheter treatment modalities for patients with congenital/structural heart disease. The laboratory is also involved in validation studies focused on innovative, non-invasive ways to assess hemodynamic data (such as cardiac output and mixed venous saturation) at the bedside or at ambulatory outpatient evaluations. Finally, the lab is involved in multicenter, safety and efficacy trials for specific devices as well as follow-up registries and outcome assessment protocols.

• Medtronic Melody Transcatheter Pulmonary Valve Trial -- a multicenter, U.S. investigational device exemption (IDE) trial involving use of the Medtronic Melody Transcatheter Pulmonary Valve in right ventricular outflow tract conduit dysfunction. Contact: William E. Hellenbrand, MD
• Medtronic Melody Post-Approval Study Program -- the primary objectives will be to gather data on the long-term clinical performance of the Melody transcatheter pulmonary valve and to assess whether or not the results obtained by the IDE centers have external validity among other centers and patients. The first study will involve continued follow-up through five years, and the second study will involve enrollment of additional subjects to be implanted among 8-10 new centers. Contact: Julie A. Vincent, MD
• Coarctation of Aorta Stent Trial (COAST) -- a multicenter trial involving use of bare metal and covered Cheatham/Platinum (CP) stents for treatment of native and recurrent aortic coarctation under an FDA IDE protocol. Contact: Julie A. Vincent, MD
• Covered Stent Compassionate Use Study -- a multicenter trial involving use of covered Cheatham/Platinum (CP) stents for primary treatment of coarctation of aorta and aortic vascular injuries. Contact: Julie A. Vincent, MD
• AGA ADO II Clinical Study -- a multicenter trial to further assess safety and efficacy of the new Amplatzer Duct Occluder II device (AGA Medical) for transcatheter closure of the patent ductus arteriosus under an FDA IDE protocol. Contact: Julie A. Vincent, MD
• ASD PMS II -- a multi-center post-market approval study involving use of Amplatzer Septal Occluder for transcatheter closure of atrial septal defects to assess long term clinical performance of the Amplatzer Septal Occluder used for transcatheter closure of atrial septal defects. Contact: William E. Hellenbrand, MD
• AGA Muscular VPA study -- a multicenter, post-market approval study involving the AGA Muscular Ventricular Septal Occluder for treatment of muscular ventricular defects. Contact: William E. Hellenbrand, MD
• Congenital Cardiac Catheterization Outcomes Project (C3PO) -- a multicenter study to assess adverse events and outcomes of diagnostic and interventional cardiac catheterizations in congenital heart disease and to report these event rates as a multi-institutional experience rather than the usual report from a single center experience. This data will also aid in the development of tools and assessing methods for risk stratification which will allow equitable comparisons of outcomes among institutions and individual practitioners. Contact: Julie A. Vincent, MD
• Balloon Angioplasty vs. Intravascular Stent Placement for Recurrent or Native Coarctation of the Aorta under the CCISC (Congenital Cardiovascular Interventional Study Consortium) -- a prospective, multicenter observational study involving 41 centers to compare surgical, balloon angioplasty, and stent placement as treatment for coarctation of the aorta in children > 12 kg. Contact: Julie A. Vincent, MD
• Non-invasive Tissue Saturation Monitor as a Surrogate for Mixed Venous Saturation in Children (Validation of Sto2 in Children). An institutional study involving collaboration between Neonatology and Cardiology services to evaluate the relationship between tissue saturation as measured by T-Stat (a non-invasive monitor and buccal probe (clip) and oximetrically measured mixed venous saturation from routine blood samples obtained from the SVC and/or PA in patients undergoing cardiac catheterization. Contacts: Ganga Krishnamurthy, MD or Julie A. Vincent, MD
• Validation of noninvasive measurement of cardiac output -- an institutional study involving collaboration between Neonatology and Cardiology services to evaluate the relationship between cardiac output (CO) measured non-invasively by electrical cardiometry with CO measured by thermodilution (TD) method and Fick method in children undergoing cardiac catheterization. Contacts: Ganga Krishnamurthy or Julie A. Vincent, MD
• Detection of Atherosclerosis with Intravascular Ultrasound (IVUS) and Cardiac Computed Tomography Angiography (CCTA) in Familial Hypercholesterolemia: A Comparative Study -- a pilot study to evaluate the presence and severity of coronary and aortic atherosclerosis in patients with homozygous and heterozygous familial hypercholesteremia using IVUS imaging with high resolution coronary CCTA and to assess whether CCTA can allow comparable imaging of coronary artery atherosclerosis with the more invasive "gold standard" IVUS with less risk to the patient. This study is being performed at the Weill Cornell campus. Contacts: Rubin S. Cooper, MD or Julie A. Vincent, MD
• Aortic Balloon Valvuloplasty: Procedural Success, Efficacy and Adverse Events: Results of a Multi-center Registry -- a multicenter study (under C3PO) to assess success, efficacy, and adverse events, and to identify risk factors or variables associated with outcome of aortic balloon valvuloplasty for patients with congenital aortic valve stenosis. Contact: Alejandro J. Torres, MD
• Pulmonary Balloon Valvuloplasty: Procedural Success, Efficacy and Adverse Events: Results of a Multi-center Registry -- a multi-center study (under C3PO) to assess success, efficacy, and adverse events, and to identify risk factors or variables associated with outcome of pulmonary balloon valvuloplasty for patients with congenital pulmonary valve stenosis. Contact: Alejandro J. Torres, MD

Electrophysiology

• Supraventricular Tachycardia Ablation in Patients with ADHD -- a retrospective review of the electrophysiology database to determine the outcome of children with ADHD undergoing electrophysiologic study and ablation of arrhythmias, and to determine how the ablation procedure influences the management of the ADHD. Contact: Leonardo Liberman, MD
• Retrospective Study of Idiopathic Left Ventricular Tachycardia in the Pediatric Population -- a multicenter study that is designed to describe the clinical presentation of patients with fascicular tachycardia; describe the outcomes of these patients with respect to medical management; and describe the outcomes of these patients with respect to interventional therapies such as ablation procedures. Contact: Leonardo Liberman, MD
• Repair of Fracture Leads -- a retrospective review of the pacemaker database to determine the long term follow-up of patients that underwent repair of pacemaker lead fracture. Contact: Leonardo Liberman, MD
• Isoproterenol Testing after Ablation of AVNRT -- a study to determine the need for testing with an infusion of isoproterenol after apparently successful ablation of atrioventricular nodal reentry tachycardia. Contact: Eric S. Silver, MD
• Use of an 8 mm Cryocatheter for Ablation of AVNRT -- a study to determine the incidence of acute success and late recurrences after ablation of atrioventricular nodal reentry tachycardia using an 8 mm catheter, and to ensure an adequate safety profile. Contact: Eric S. Silver, MD
• Electrophysiologic Study in Pediatric Heart Transplant Recipients -- a prospective study in pediatric patients with heart transplants to determine the electrophysiologic properties of the transplanted heart at the time of an endomyocardial biopsy. Contact: Leonardo Liberman, MD
• Double Loops in Transvenous Pacemaker Leads -- a retrospective review of patients that underwent placement of a transvenous pacemaker lead with a double loop technique to determine the long-term outcome of such an approach. Contact: Leonardo Liberman, MD

Pediatric Cardiopulmonary Laboratory

• Measured Oxygen Consumption during the Six Minute Walk Test (6MWT) in Patients with Pulmonary Arterial Hypertension (PAH) -- a study designed is to measure oxygen consumption during the 6MWT in patients with PAH. We hope to demonstrate a relationship between 6MWT distance, Borg Dyspnea Score, %peakVO2 and peak VO2 in repeated measurement in the same subject over time. Contact: Robert Garofano, PhD

General Pediatric Cardiology

• Pediatric Systemic Hypertension -- a prospective multi-center NIH funded study designed to evaluate a non-invasive behavioral modification therapy in the treatment of hypertension in children. Contact: Thomas J. Starc, MD, MPH

Cardiovascular Genetics
Columbia University is one of the five Pediatric Cardiac Genomics Consortium centers funded by the NHLBI to elucidate the underlying genetic basis for cardiac disease in children. Working with investigators at Harvard University, Yale University, Mount Sinai, and the Children's Hospital of Philadelphia, we are studying children with structural heart disease and their parents using the most sophisticated modern genetics methods including copy number variation, genetic association studies, and sequencing of candidate genes and whole exomes. These studies seek to identify what causes congenital heart disease, to assist families in determining prognosis, and to assess risk of having another child with congenital heart disease. Contact: Wendy Chung, MD, PhD

Developmental Biology
In the Developmental Biology research program within the Division of Cardiology, we aim to further our understanding of the genetic determinants of cardiac morphogenesis through the study of model organisms. The transparent zebrafish embryo is ideal, as it allows for microscopic observation of the developing heart throughout embryogenesis. Furthermore, Zebrafish do not require a functional cardiovascular system for survival until well after cardiac chamber formation is complete. The large volume of embryos that are readily obtained in the laboratory provides us with a powerful tool for genetic analysis. Currently, our research is focused on the study of NKX2.5, a cardiac-specific homeodomain transcription factor that is known to cause different types of heart defects. As additional causative genes are identified in human genetics, we will take advantage of the benefits of the zebrafish model as a means to understand the mechanisms underlying congenital heart disease. Contact: Kimara L. Targoff, MD