Highlights of Research, Studies, and Clinical Trials

The Cardiac Center actively enrolls patients and healthy control subjects for a wide variety of research, studies, and clinical trials. The purpose is to better understand what causes heart defects, create better diagnostic tools and cutting-edge therapies, and to improve long-term outcomes for patients.

The Cardiac Center is home to hundreds of new initiatives that will transform the care of children with congenital and acquired heart disease and adults with congenital heart disease. Here are some highlights:

Angiogenesis in Single Ventricle Congenital Heart Defects

This study aimed at developing a biorepository of blood samples from various vascular compartments of patients born with only a single heart ventricle, in order to better explore the foundations of angiogenic disorders seen in this unique patient population.

Impact of a Lower Extremity-Focused Exercise Training Program on Leg Muscle Mass and Oxygen Consumption in Adolescent Patients with Fontan Physiology

Researchers assessed the change in skeletal muscle mass through dual energy absorptiometry (DXA) after a 24-week, lower extremity-focused exercise training program in adolescent patients who have undergone the Fontan procedure – a surgery designed to reroute blood flow in the heart. The aim was to asses changes in functional health as well as to assess the feasibility of a collaborative exercise program in adolescent Fontan patients through both CHOP and Cincinnati Children's Hospital Medical Center.

Imaging and Biomarker Evaluation of Hepatic Stiffness in Children Enrolled in the Fontan Udenafil Exercise Longitudinal Extension Trial (FALD)

The goal was to learn whether the medication called udenafil can make the liver less stiff in children who have undergone the Fontan operation, a surgical procedure which reroutes blood flow in the heart.

Phase IIb Study of Intramyocardial Injection of Autologous Umbilical Cord Blood Derived Mononuclear Cells during Stage II Surgical Repair of HLHS

The aim of this study was to determine if autologous stem cells from umbilical cord blood can strengthen the muscle of the right side the heart. This study will help to determine whether stem cells are effective to use as an additional treatment for the management of hypoplastic left heart syndrome.

Dyslipidemia of Obesity Intervention in Teens DO IT! Trial

This study aimed to compare the effectiveness of the medication pitavastatin versus placebo on vascular measures in at least 354 obese adolescents across multiple sites who also present with abnormally high levels of fats in the bloodstream (called “lipids”) – that is, those patients with a body mass index > 95th percentile as well as having high non-HDL-C + high TG/HDL-C ratio or low HDLC.

Impact of Genotype on Outcome in Tetralogy of Fallot

The main objective of this study was to determine if genotype such as 22q11 deletion syndrome is associated with prenatal, post-operative, and right ventricular mechanics in patients with specialized heart defects undergoing surgical repair.

Quality of Life After Heart Transplant

The overall goal of this study is to develop a more comprehensive understanding of the determinants of health-related quality of life in pediatric patients after orthotopic heart transplantation – and specifically how psychological factors and social environment modify quality of life. This study proposed to measure general and cardiac disease-specific quality of life in children and adolescents who have had a heart transplant.

Heart Health Screening of Children for Sudden Cardiac Arrest

There were several objectives in this study: to improve and validate electrocardiogram (ECG) screenings; to compare different ECG screening programs with the customary care in the US used to screen youth; to provide a community-based intervention to increase awareness of the heart health impact of obesity and hypertension in children and youth; and, finally, to determine the effectiveness of an educational program to train pediatricians and nurse practitioners to read ECGs in the home vs. reading of ECGs by a pediatric cardiologist.

Gene Therapy for Male Patients with Danon Disease

The goal was to characterize the safety and toxicity associated with infusion of a recombinant adeno-associated virus serotype 9 (rAAV9) capsid containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene, as well as to evaluate low and high single intravenous doses of investigational product with respect to safety, toxicity, and preliminary efficacy. Additionally, researchers investigated if infusion results in cardiomyocyte (and skeletal muscle) transduction and gene expression to determine if there is correction of disease-associated histologic abnormalities, and therefore to enable preliminary characterization of the extent of cardiomyocyte molecular and histologic correction.

Examining Psychological and Physiologic Manifestations of Parent Stress

The primary objective of this pilot project was to examine the relationship of self-reported perceived stressors and stress response with the psychoendocrine biomarker of cortisol in parents of infants hospitalized for neonatal cardiac surgery at three distinct time points: within one week after the infant’s surgery, within 72 hours of discharge, and 3 months after discharge. The primary aims include an exploration (for both mothers and fathers) of the relationship of cortisol awakening response (CAR) and a) self-reported perceived stressors b) state anxiety and c) depressive symptoms. Additionally, researchers sought to learn about the relationship of CAR with the combination of self-reported perceived stressors, state anxiety, and depressive symptoms. The secondary aim included an exploration, for both mothers and fathers, of the relationship of CAR with a) state anxiety b) depressive symptoms and c) post-traumatic stress disorder (PTSD).

Medtronic Harmony™ Transcatheter Pulmonary Valve Clinical Study

The purpose of this study was to see if the Medtronic Harmony™ Transcatheter Pulmonary Valve (Harmony TPV) and Delivery System is safe and how well it works. This device is for patients who have congenital heart disease with a missing or narrowed pulmonary valve, and are without a conduit (a way of connecting the right ventricle and the pulmonary artery to assist blood flow to the lungs). These patients sometimes need an operation to treat a leaky pulmonary valve. The standard treatment has been to implant a new valve through open heart surgery. The Harmony TPV used in this study was a substitute for open heart surgery, and the device was implanted through catheters inserted via blood vessels in the groin or neck.

Multicenter Study of Congenital Pulmonic Valve Dysfunction Studying the SAPIEN 3 Transcatheter Heart Valve with the Alterra Adaptive Prestent

The purpose of this study was to see if the Edwards Alterra Adaptive Prestent (Alterra Prestent) and Delivery System is safe and how well it works when used with the SAPIEN 3 Transcatheter Heart Valve. This device is for patients who have congenital heart disease with a missing or narrowed pulmonary valve, and are without a conduit (a way of connecting the right ventricle and the pulmonary artery to assist blood flow to the lungs). These patients sometimes need an operation to treat a leaky pulmonary valve. The standard treatment has been to implant a new valve through open heart surgery. The Alterra Prestent used in this study was a substitute for open heart surgery, implanted through catheters inserted via blood vessels in the groin or neck. The stent allows the SAPIEN 3 Valve to be implanted in a pulmonary artery that is the wrong size for any currently approved transcatheter heart valve.

Outcomes after the Norwood Procedure

We are currently undertaking a formal review of all Norwood procedures performed at CHOP since January 1, 1984. The Norwood is the first of three surgeries designed to create a new functional route in the heart for patients with hypoplastic left heart syndrome. The first phase of the review is a chart focused on perioperative outcomes after the Norwood. The second phase will be a chart review focused on the superior cavo-pulmonary connection and the Fontan procedure. We will then contact all survivors to update vital status and assess medical status and quality of life. Finally, we propose to invite all survivors to return for a detailed cardiac evaluation and formal neurobehavioral assessment.

Bioprosthetic Valve Use in Congenital Heart Disease

Bioprosthetic valve use and durability remains a critical problem in young patients with congenital heart disease. We are actively involved in studies examining the timing of pulmonary valve replacement in young patients with Tetralogy of Fallot (TOF) heart defects, as well as long-term outcomes for patients undergoing tissue valve replacement in the aortic position.

Fetal Neuroprotection

The goal of this study is to test the hypothesis that maternal therapy with vaginal progesterone during the third trimester will improve neurodevelopmental outcomes by: 1) a direct neuroprotective effect; 2) prolonging pregnancy; and 3) enhancing oligodendrocyte maturation. Mothers are randomized to therapy with vaginal progesterone or placebo beginning prior to 28 weeks GA (gestational age) and continuing to 39 weeks GA. The primary outcome is neurodevelopmental evaluation at 18 months of age using the Bayley-III cognitive and language scales. Brain development is assessed by serial fetal and post-natal brain MRIs.

Birth Defect Biorepository

We inaugurated a multidisciplinary approach to the study of birth defects at CHOP. Major structural birth defects occur in approximately 1 in 40 live births. These anomalies have a significant risk of mortality, morbidity, and long-term disability in the survivors, and an enormous impact on the lives of these children and their parents. The primary objective of this project is to provide a mechanism to support future research by collecting and storing biospecimens and clinical information about subjects with birth defects.

Adult Congenital Heart Disease

With a rapidly increasing population, many questions remained unanswered regarding the clinical outcomes, management strategies, best practices and standards of care for this complex group of patients. Specific areas of focus include outcomes studies in adult neurodevelopment, Fontan sequelae and pregnancy outcomes in adulthood and multi-organ transplant in adult congenital patients.

Development of Animal Models to Investigate the Impact of Congenital Heart Disease on Brain Development

Lack of animal models has significantly limited our ability to investigate the impact of congenital heart disease (CHD) on fetal brain development. The Children’s Hospital of Philadelphia has developed a pumpless extra-uterine system to physiologically support an extremely premature lamb, mimicking the intrauterine environment and allowing physiologic support. Development and validation of this animal model will provide a tremendous opportunity to improve our understanding of the mechanisms by which CHD impacts brain development as well as a unique platform to test new neuroprotective therapies.

Perioperative Neuroprotection

Understanding neurologic injury following cardiac surgery is a vital first step toward developing novel and personalized treatment strategies to prevent injuries. These studies offer novel insights into the poorly understood mechanism of ischemia-reperfusion injury that may lead to neuronal death and neurological disability. Future work will further characterize the mitochondrial response to different bypass in an effort to further understand the optimal perfusion strategy for neuroprotection in neonatal cardiac surgery. The goal is to develop new therapeutic strategies to preserve mitochondrial health which may mitigate brain injury in cardiac surgical patients.

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