Cardiomyopathy (VVV) Publications

• Reproducibility of Left Ventricular Dimension Versus Area Versus Volume Measurements in Pediatric Patients With Dilated Cardiomyopathy. E.S. Selamet Tierney, Circ Cardiovasc Imaging 2017; 10(11). pii: e006007.
  There are multiple echocardiographic methods in common clinical use for measuring left ventricular size and function. Clinical management is often based on both individual evaluations and longitudinal trends, but it is generally not possible or practical to have the same personnel perform and interpret the echocardiographic assessment over time. Using data from the PHN’s, Ventricular Volume Study in children with dilated cardiomyopathy, we investigated the impact of observer and sonographer variation on reproducibility of dimension, area, and volume methods to determine the most reproducible method for both individual and sequential evaluations. Compared to dimension and area methods, left ventricular measurements by volume method have the best reproducibility in settings where assessment is not performed by the same personnel. In an era in which left ventricular function is not assessed routinely by volume methods (i.e., ejection fraction) in many pediatric echocardiographic laboratories, this study provides important information on reproducibility that could impact long-term management of pediatric dilated cardiomyopathy.
• Systolic-diastolic functional coupling in healthy children and in those with dilated cardiomyopathy. M. K. Friedberg, J Appl Physiol 2016; 120(11):1301-1318.
• The reproducibility and absolute values of echocardiographic measurements of left ventricular size and function in children are algorithm dependent. R. Margossian, J Am Soc Echocardiogr 2015; 28(5):549-558. Epub 2015 Feb 27.
• Predictors of disease progression in pediatric dilated cardiomyopathy. K. Molina, Circ Heart Fail 2013; 6(6): 1214–1222.
• Variability of M-mode versus two-dimensional echocardiography measurements in children with dilated cardiomyopathy. C. Lee, Pediatr Cardiol 2014; 35(4):658-67. Epub 2013 Nov 22.
• The Ventricular Volume Variability Study of the Pediatric Heart Network: Study design and impact of beat averaging and variable type on the reproducibility of echocardiographic measurements in children with chronic dilated cardiomyopathy. S. Colan, J Am Soc Echocardiogr 2012; 25:842-54.

Editorial

• Left Ventricular Dysfunction is Associated with Intraventricular Dyssynchrony by 3-Dimensional Echocardiography in Children. G. Baker, J Am Soc Enchocardiogr 2008; 21(3):230-233.
  “Dyssynchrony” means that parts of the heart do not squeeze at the same time. This causes less efficient ejection of blood and contributes to heart failure. There is little data on dyssynchrony in children. This small study looked at whether 3-dimensional echocardiography (heart ultrasound) can be used to identify dyssynchrony in healthy children and children with poor heart function. The results show that 3D echocardiography can be used to look at dyssynchrony in children, and that patients with poorer heart function have more dyssynchrony.

Collaborative Learning Publications

• Utilizing a Collaborative Learning Model to Promote Early Extubation Following Infant Heart Surgery. W. T. Mahle, Pediatr Crit Care Med; 2016 Oct;17(10):939-947.
• Rationale and methodology of a collaborative learning project in congenital cardiac care. M. J. Wolf, Am Heart J; 2016 Apr;174:129-37.

Echo Z-Score Publications

• Relationship of Echocardiographic Z Scores Adjusted for Body Surface Area to Age, Sex, Race, and Ethnicity: The Pediatric Heart Network Normal Echocardiogram Database. L. Lopez, Circ Cardiovasc Imaging 2017; 10(11):e006979.

Fontan Publications

• Assessment of Diastolic Function in Single-Ventricle Patients After the Fontan Procedure. R. Margossian, J Am Soc Echocardiogr 2016 Nov;29(11):1066-1073.
• Factors Impacting Echocardiographic Imaging after the Fontan Procedure: A Report from the Pediatric Heart Network Fontan Cross-Sectional Study. R. Williams, Echocardiography 2013; 30:1098-1106.
• Functional health status in children and adolescents after Fontan: Comparison of generic and disease-specific assessment. B. McCrindle, Cardiol Young 2014; 24(3): 469–477.
• Cardiac performance and quality of life in patients who have undergone the Fontan procedure with and without prior superior cavopulmonary connection. A. Atz, Cardiol Young 2013; 23(3): 335–343.
• Comparison of Fontan Survivors with and without Pacemakers: A Report from the Pediatric Heart Network Fontan Cross-sectional Study. R. Williams, Congenit Heart Dis 2013;8(1): 32–39.
• Non-Geometric Echocardiographic Indices of Ventricular Function in Patients with a Fontan Circulation. J. Rhodes, J Am Soc Echocardiogr 2011; 24:1213-9.
• Practice variability and outcomes of coil embolization of aortopulmonary collaterals before Fontan completion: A report from the Pediatric Heart Network Fontan Cross-Sectional Study. P. Banka, Am Heart J 2011; 162:125-130.
• Late Status of Fontan patients with Persistent Surgical Fenestration. A. Atz, J Am Coll Cardiol 2011; 57:2437-43.
• Factors associated with serum brain natriuretic peptide levels after the Fontan procedure. A. Atz, Congenit Heart Dis 2011; 6:313-321.
• Anthropometric measures after the Fontan procedure: Implications for suboptimal functional outcome. M. Cohen, Am Heart J 2010; 160:1092-1098.e1.
• The Fontan patient: inconsistencies in medication therapy across seven pediatric heart network centers. P. Anderson, Pediatr Cardiol 2010; 31(8): 1219–1228.
• Relation of the size of secondary ventricles to exercise performance in children after a Fontan operation. A. Prakash, Am J Cardiol 2010; 106(11):1652-6.
• Arrhythmias in a contemporary Fontan cohort: prevalence and clinical associations in a multi-center cross-sectional Study. E. Stephenson, J Am Coll Cardiol 2010; 56:890-6.
• Impaired Power Output and Cardiac Index with Hypoplastic Left Heart Syndrome: A Magnetic Resonance Imaging Study. K. Sundareswaran, Ann Thorac Surg 2006; 82(4):1267-75; discussion 1275-77.
• Flow Study of an Extra-Cardiac Connection with Persistent Left Superior Vena Cava. D. de Zélicourt, J Thorac Cardiovasc Surg 2006; 131:785-91.
• Laboratory Measures of Exercise Capacity and Ventricular Characteristics and Function are Weakly Associated with Functional Health Status After Fontan Procedure. B. McCrindle, Circulation 2010; 121:34-42.
  This study looked at how the well being of children who were in the Fontan study related to the test results from echocardiography, MRI, blood and exercise tests. The results showed that the results of these tests were only weakly associated with health status. This suggests that these tests may not be good markers for functional health status.
• Parent Versus Child-Reported Functional Health Status After the Fontan Procedure. L. Lambert, Pediatrics 2009; 124:e942-949.
  Children ages 10-18 enrolled in the Fontan study and their parents completed forms to assess the child’s health status. Parents’ perceptions of the functional health status of their children after the Fontan procedure were worse than the children’s perceptions of their own well being in several areas.
• Comparison of Echocardiographic and Cardiac Magnetic Resonance Imaging Measurements of Functional Single Ventricular Volumes, Mass, and Ejection Fraction (From the Pediatric Heart Network Multicenter Fontan Cross-Sectional Study). R. Margossian, Am J Cardiol 2009; 104:419-428.
  The size and function of a single heart pumping chamber (ventricle) are key elements when managing patients after the Fontan procedure. Children in the Fontan study had echocardiograms and MRIs performed as part of the study. This article describes how closely the measurements compare between different doctors who read the studies.
• Functional State Following the Fontan Procedure. I. Williams, Cardiol Young 2009; 15:1-11.
  Despite improvements in outcomes after surgery, the functional state varies in children who have had the Fontan procedure. This study developed a scoring system for overall function, looking at how the pumping chamber squeezes, the ability to exercise, physical well-being, and certain lab tests. Lower overall function after surgery was found in children who have a right heart pumping chamber, heart pressures that are higher than normal, lower oxygen levels before surgery, abnormal heart rhythms after surgery, and lower income of their caregiver.
• Functional Status, Heart Rate, and Rhythm Abnormalities in 521 Fontan Patients 6-18 Years of Age. A. Blaufox, J Thorac Cardiovasc Surg 2008; 136:100-107.
  Problems with heart rate and rhythm are common after the Fontan procedure. The purpose of this study was to see if daily health status in children enrolled in the Fontan study was affected by heart rate or rhythm disorders. Researchers found that a lower resting heart rate and a higher heart rate during exercise were only weakly associated with better physical health. Therefore, other factors may have more impact on how children function after then Fontan procedure. 
• Contemporary Outcomes After the Fontan Procedure: A Pediatric Heart Network Multicenter Study. P. Anderson, J Am Coll Cardiol 2008; 52:85-98.
  The Fontan study was designed to study children born with a single ventricle or heart pumping chamber who underwent a type of surgery called the Fontan procedure Data was collected from 546 children between 6 and 18 years of age about their heart structure and function after surgery, ability to exercise, heart rhythm and certain lab tests. Questions were asked to assess physical, mental, and emotional well being. The study showed that most Fontan survivors had a normal sense of well being. Most had normal ability for the heart to squeeze, but the majority had decreased relaxation of the heart muscle. Ability to exercise was also decreased in most. Children with a single right ventricle (pumping chamber) had decreased function of the heart and its valves compared with children with a single left ventricle. If the Fontan procedure was done at an older age, heart valves did not work as well and children were less likely to have a normal heart rhythm.
• A Cross-Sectional Study of Exercise Performance During the First 2 Decades of Life After the Fontan Operation. S. Paridon, J Am Coll Cardiol 2008; 52:99-107.
  This study discusses the exercise performance of a large group of children in the Fontan study. Of the 546 children in the study, 411 had exercise testing performed, and most (60%) were not able to exercise to peak levels. Those who were able to reach peak exercise were more likely to be older. Many reported fatigue as a reason for not reaching peak exercise. The wide range of performance was found to be related to the whether the heart is able to increase the amount of blood squeezed out of the pumping chamber (stroke volume). The study also showed that as males go through puberty and gain more muscle, the heart after a Fontan procedure may not be able to keep up with increased demands, making exercise more difficult. 
• The Fontan Procedure Our Odyssey Continues. C. Backer, J Am Coll Cardiol 2008; 52:114-116.
  This article describes the results of the Fontan study and how those results may change the way we care for children who will need to have the Fontan procedure.
• Functional State of Patients with Heterotaxy Syndrome Following the Fontan Operation. A. Atz, Cardiol Young 2007; 17 Suppl 2:44-53.
  Children with heterotaxy syndrome have been found to have poorer outcomes compared to children with other complex heart problems, even if those children undergo the same surgeries. Eight percent of children in the Fontan study were found to have heterotaxy syndrome. Those children with heterotaxy were compared to children in the Fontan study without heterotaxy, in regards to their medical and surgical history, heart structure and function, ability to exercise, and health status. The study showed that there were no real differences between the two groups in the children’s sense of physical and psychosocial well-being or ability to exercise. 
• Physical Activity Levels in Children and Adolescents are Reduced After the Fontan Procedure, Independent of Exercise Capacity, and are Associated with Lower Perceived General Health. B. McCrindle, Arch Dis Child 2007; 92:509-514.
  The Pediatric Heart Network studied 147 of the children in the Fontan study to see how physically active they were on a daily basis. The researchers found that these children participated in physical activity far less often than healthy children, even if their exercise tests showed that they are able to exercise. Children who spent less time being physically active believed they were less healthy overall, whereas children who were not able to exercise as well not only believed they were less healthy, but also had lower level of physical function and self-esteem. 
• Design of a Large Cross-Sectional Study to Facilitate Future Clinical Trials in Children with the Fontan Palliation. L. Sleeper, Am Heart J 2006; 152:427-433.
  This article describes how the Fontan study was designed and implemented in the Pediatric Heart Network. The purpose of the study was to determine whether clinical measures of how well the heart is working (such as lab tests, exercise testing, and echocardiogram) compare with health status (quality of life) in patients who have had a Fontan procedure for congenital heart disease. The data will help researchers design future clinical trial. 
• Relationship of Patient and Medical Characteristics to Health Status in Children and Adolescents after the Fontan Procedure. B. McCrindle, Circulation 2006; 113:1123-1129.
  Children with a single ventricle (heart pumping chamber) who have undergone the Fontan procedure are at risk of having poor health because of frequent hospitalizations and surgeries, decreased ability to exercise, and other medical problems. Parents of children in the Fontan study answered questions about their child’s physical activity, behavior, emotions and self-esteem. The results showed that as a group, children who have had the Fontan procedure have more problems with vision, speech, hearing, attention, learning, behavior, anxiety and depression compared to children in the general population. The impact of these other problems was made worse by having a lower family income. Future research is needed to identify ways to diagnose, prevent and treat these problems and to recognize the impact they have on children who have had the Fontan procedure.
• Protein-losing enteropathy after fontan operation: investigations into possible pathophysiologic mechanisms. A. Ostrow, Ann Thorac Surg 2006; 82:695-700.

• Sustained Effects of Cardiac Rehabilitation in Children with Serious Congenital Heart Disease. J. Rhodes, Pediatrics 2006; 118(3):e586-593.
  Previous studies have shown immediate benefits when children with congenital heart disease are enrolled in a cardiac rehabilitation (exercise) program. This study aimed to see if the benefits lasted after the exercise program ended. The results showed, compared with children who did not undergo cardiac rehabilitation after the Fontan procedure, children who did participate had significant improvements in exercise function, behavior, self-esteem and emotional state 6 months after their program ended.
• Impact of Cardiac Rehabilitation on the Exercise Function of Children with Serious Congenital Heart Disease. J. Rhodes, Pediatrics 2005; 116(6):1339-1345.
  Children with congenital heart disease (CHD) often can’t exercise as well as their peers. Part of this may be due to their heart defect and part may be that they may not be very physically active. A 12-week cardiac rehabilitation program was designed to see if children could improve their ability to exercise safely. Sixteen patients completed the program. Improvements were found in 15 of 16 patients and no patient had any heart problems from the exercise.

Fontan Follow-up Study Publications

• Assessment of Quality of Life in Young Patients with Single Ventricle after the Fontan Operation. K. Uzark, J Pediatr 2016; 170:166-172 Epub 2015 Dec 10.
• Survival data and predictors of functional outcome an average of 15 years after the Fontan procedure: The Pediatric Heart Network Fontan cohort. A. Atz, Congenit Heart Dis 2015; 10(1):E30-42.
• The relationship of patient, medical and laboratory characteristics to changes in functional health status in children and adolescents after the Fontan procedure. B. McCrindle, Pediatr Cardiol 2014; 35(4):632-640.

Fontan 3

• Longitudinal outcomes of patients with Single Ventricle after the Fontan procedure. A. Atz, J Am Coll Cardiol 2017; 69(22):2735-2744.

FUEL Publications

• Design and rationale of the Fontan Udenafil Exercise Longitudinal (FUEL) trial. D.J. Goldberg, Am Heart J. 2018 Jul; 201:1-8.
  This manuscript describes the design of the randomized controlled trial of udenafil in children and adolescents with single ventricle heart disease who have undergone the Fontan operation. This study is powered to detect changes in exercise capacity, ventricular performance, and vascular function. These outcomes are important long-term determinants of health, and changes in these outcomes will be important in understanding whether udenafil has a role as a maintenance medication for this population. The FUEL trial is the largest multi-center randomized, controlled medication trial in congenital heart disease to date. This trial will help to determine whether routine udenafil use is associated with improvement in outcomes associated with long-term health in children and adolescents with single ventricle heart disease who have undergone the Fontan operation. Thirty centers from North America and Korea are participating in the FUEL trial.

Kawasaki Disease (KD) Publications

• Predictors of coronary artery visualization in Kawasaki disease. R. Margossian, J Am Soc Echocardiogr 2011; 24(1):53-9.
• Evaluation of Kawasaki Disease Risk Scoring Systems for Intravenous Immunoglobulin Resistance. L. Sleeper, J Pediatr 2011; 158:831-5.
• Non-Coronary Cardiac Abnormalities are Associated with Coronary Artery Dilation and with Laboratory Inflammatory Markers in Acute Kawasaki Disease. B. Printz, J Am Coll Cardiol 2011; 57:86-92.
• Associated Symptoms in the Ten Days Before Diagnosis of Kawasaki Disease. A. Baker, J Pediatr 2009; 154(4):592-595.
  Many children with Kawasaki disease (KD) have other symptoms that may lead to a delay in the diagnosis of KD. This study investigated common symptoms in children in the KD study (in addition to the symptoms of KD) in the 10 days before they were diagnosed with KD. Symptoms reported were irritability, vomiting, decrease in food/fluid intake, coughing, diarrhea, runny nose, weakness, stomach pain, and joint pain. Symptoms of KD can often be accompanied by symptoms commonly found in other common childhood illnesses. Clinicians should consider the diagnosis of KD, even when other common symptoms are present.
• Coronary Artery Involvement in Children with Kawasaki Disease: Risk Factors from Analysis of Serial Normalized Measurements. B. McCrindle, Circulation 2007; 116:1-6.
  This study looked at how coronary artery size changes during when a child has Kawasaki Disease (KD) by performing echocardiograms at the time of diagnosis, at one week and five weeks after diagnosis. The results showed that, in most patients, the coronary arteries are most dilated at the time of diagnosis of KD and they decrease in size over time. The KD study also showed that aneurysms (bulges or outpouches) in the coronary arteries were infrequent.
• Delayed Diagnosis of Kawasaki Disease: What Are the Risk Factors?. L. Minich, Pediatrics 2007; 120(6):e1434-40.
  Late diagnosis of Kawasaki Disease (KD) increases the risk that a child might have enlargement or aneurysms (out-pouching) of their coronary arteries. This study tried to see how many children in the KD study had a late diagnosis and what factors contributed to a late diagnosis. Being less than 6 months of age, living a greater distance from the hospital and having fewer symptoms (incomplete KD) increased the likelihood of late diagnosis.
• Randomized Trial of Pulsed Corticosteroid Therapy for Primary Treatment of Kawasaki Disease. J. Newburger, N Engl J Med 2007; 356(7):663-675.
  Children with Kawasaki Disease (KD) are at risk for developing aneurysms (out-pouchings) and enlargement of the coronary arteries, the arteries which bring blood and oxygen to the heart muscle itself. Medications are used to reduce the risk of damage to the coronary arteries and to decrease inflammation. Yet, some children still develop aneurysms and coronary artery enlargement. This trial tested whether adding another type of medication (a corticosteroid) to the standard treatment of aspirin and immune globulin would decrease the amount of coronary artery dilation. The results did not support the use of a steroid in addition for the routine treatment of children with KD.
• Treatment of Kawasaki Disease: Response to Letter to the Editor. J. Newburger, N Engl J Med 2007; 356(26):2748.

Marfan Publications

• Predictors of Rapid Aortic Root Dilation and Referral for Aortic Surgery in Marfan Syndrome. A. Hoskoppal, Pediatr Cardiol 2018 Jun 11. doi: 10.1007/s00246-018-1916-6.
  This was a secondary analysis of the PHN randomized clinical trial of atenolol vs. losartan in patients with Marfan syndrome that attempted to identify factors that predict rapid aortic root dilation and referral for aortic surgery. We found some statistically significant but only weakly predictive associations between more rapid aortic root dilation and older age, non-white race, and one aortic measurement: higher sinotubular junction z-score. We found similarly statistically significant but only weakly predictive associations between referral for aortic root surgery and some aortic measurements (larger aortic root diameter, higher ascending aorta z-score, and higher ratio between the diameters of the sinotubular junction and ascending aorta). Future studies may clarify whether monitoring generalized proximal aortic dilation and effacement of the sinotubular junction will help to risk-stratify young patients with Marfan syndrome and inform medical and surgical management.
• Influence of Aortic Stiffness on Aortic-Root Growth Rate and Outcome in Patients With the Marfan Syndrome. ES. Selamet Tierney, Am J Cardiol 2018 May 1;121(9):1094-1101.
  The PHN randomized trial of atenolol versus losartan in Marfan Syndrome showed no treatment differences in the rates of aortic-root growth or clinical outcomes. This analysis examined treatment effects on aortic stiffness and determined whether baseline aortic stiffness predicts aortic-root growth and clinical outcomes. There was no treatment effect on the rate of change for ascending-aorta stiffness index, aortic-root elastic modulus, or ascending-aorta elastic modulus. We found that atenolol therapy was associated with a fall in aortic-root stiffness index, while losartan therapy was not. Higher baseline aortic-root stiffness index and elastic modulus were associated with a smaller decrease in aortic root z-score and increased risk for clinical outcomes. These data suggest that non-invasive aortic stiffness measures may identify patients at higher risk for progressive aortic enlargement and adverse clinical outcomes, potentially allowing for closer monitoring and more aggressive therapy for such patients.
• Atenolol versus Losartan in Children and Young Adults with Marfan's Syndrome. R. Lacro, N Engl J Med 2014; 371:2061-2071.
• Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy. R. Lacro, Am Heart J 2013; 165:828-835.e3.
• Echocardiographic Methods, Quality Review, and Measurement Accuracy in a Randomized Multicenter Clinical Trial of Marfan Syndrome. E. Selamet Tierney, J Am Soc Echocardiogr 2013; 26(6):657-666.
• Rationale and Design of a Randomized Clinical Trial of B-Blocker Therapy (Atenolol) Versus Angiotensin II Receptor Blocker Therapy (Losartan) in Individuals with Marfan Syndrome. R. Lacro, Am Heart J 2007; 154:624-631.
  The leading cause of death in people with Marfan syndrome is dilation, tearing and rupture of the aorta, the large artery that delivers blood from the heart to the body. Recent studies in mice with Marfan syndrome showed that treatment with Losartan, a medication used to treat high blood pressure, prevented dilation and improved the structure of the wall of the aorta. This article describes the design of a trial to compare Losartan to the standard medication (Atenolol) for patients with Marfan syndrome. The goal of the trial is to follow over 600 children and young adults for 3 years to determine which drug does a better job slowing the rate of growth of the aorta.

Mitral Regurgitation (ACE-I in MR) Publications

• Challenges in echocardiographic assessment of mitral regurgitation in children after repair of Atrioventricular Septal Defect. A. Prakash, Pediatr Cardiol 2012; 33:205-214.
• Surgical interventions for Atrioventricular Septal defect subtypes: The Pediatric Heart Network experience. A. Kaza, Ann Thorac Surg 2011;92:1468-75.
• Surgical management of complete atrioventricular septal defect: Associations with surgical technique, age and Trisomy 21. A. Atz, J Thorac Cardiovasc Surg 2011; 141:1371-9.
• Lessons learned from a pediatric clinical trial: The Pediatric Heart Network Angiotensin Converting Enzyme Inhibition in Mitral Regurgitation Study. J. Li, Am Heart J 2011; 161:233-40.
• Partial and Transitional Atrioventricular Septal Defect Outcomes. L. Minich, Ann Thorac Surg 2010; 89:530-536.
  There have been many improvements in the surgery and care of children with atrioventricular septal defects (AVSD. This article describes the outcomes at 1 and 6 months after repair for children with two particular types of AVSD: partial and transitional AVSDs. Children had short hospital stays and few adverse events around the time of surgery. Also, children who were growing poorly before surgery showed good catch-up growth if the surgery was performed between 3 and 18 months of age. Some children have leaking of the left-sided atrioventricular valve after surgery, particularly if surgery is performed after age four.

Multi Study (ISV-SVR-SVR II) Publications

• Adrenergic receptor genotypes influence postoperative outcomes in infants in the Single-Ventricle Reconstruction Trial. R. Ramroop, J Thorac Cardiovasc Surg. 2017; 154(5):1703-1710.e3.

Normal Electrocardiogram (ECG) Project

• Electrocardiograms in Healthy North American Children in the Digital Age. E.V. Saarel, Circ Arrhythm Electrophysiol 2018 Jul;11(7):e005808.
  Electrocardiography is a cornerstone in the cardiac evaluation of children. Wide variation in previously published data, much of which was obtained before the digital era, provided a strong motivation to obtain more reliable data on electrocardiogram (ECG) measurements in healthy children from North America. This study found that most ECG measurements varied by sex and race and differed from prior studies done in smaller, more racially and ethnically homogeneous populations. This study provides valuable data that can be used clinically for interpreting pediatric ECGs in the modern era for diagnosis or screening of heart disease in North America, particularly for Long QT syndrome and left ventricular hypertrophy.

PHN Scholars Publications

• The Pediatric Heart Network Scholar Award programme: a unique mentored award embedded within a multicentre network. L.L. Minich, Cardiol Young 2018 Jun;28(6):854-861.
  The Pediatric Heart Network designed a career development award to train the next generation of clinician-scientists in pediatric cardiology-related research, a historically underfunded area. This manuscript described strengths and weaknesses of the program and the scholars’ academic achievements for the first two funding cycles. Strengths included clarity and fairness of the review, but feedback on the application was not considered useful. The highest rated benefits were expanding the scholar’s collaborative network and increasing publication potential. The 13 scholars were first/senior authors for 97 abstracts and 109 manuscripts, served on 22 PHN committees, and were awarded $9,673,660 in subsequent extramural funding for a return of ~$10 for every Scholar dollar spent.

Residual Lesion Score (RLS) Publications

• Completeness and Accuracy of Local Clinical Registry Data for Children Undergoing Heart Surgery. M. Nathan, Ann Thorac Surg 2016 Oct 7. pii: S0003-4975(16)30916-X.

Single Ventricle (ISV) Publications

• Translating clinical trials into clinical practice: a survey assessing the potential impact of the Pediatric Heart Network Infant Single Ventricle Trial. V. Zak, Cardiol Young 2017; 27(7):1265-1270.
• The Effect of the Superior Cavopulmonary Anastomosis on Ventricular Remodeling in Infants with Single Ventricle. R. Margossian, J Am Soc Echocardiogr 2017; 130(7):699-707.e1.
• Growth Asymmetry, Head Circumference, and Neurodevelopmental Outcomes in Infants with Single Ventricles. T. Miller, J Pediatr 2016; 168:220-225. Epub 2015 Oct 17.
• Neurodevelopmental outcomes after cardiac surgery in infancy. J. Gaynor, Pediatrics 2015; 135(5):816-25.
• Factors Associated with Serum B- type Natriuretic Peptide Levels in Infants with Single Ventricle. R. Butts, Pediatr Cardiol 2014; 35(5):879-87.
• The association of fetal cerebrovascular resistance with early neurodevelopment in single ventricle congenital heart disease. I. Williams, Am Heart J 2013; 165(4):544-550.e1.
• Superior cavopulmonary anastomosis timing and outcomes in infants with single ventricle. J. Cnota, J Thorac Cardiovasc Surg 2013; 145(5): 1288–1296.
• Association of impaired linear growth and worse neurodevelopmental outcome in infants with single ventricle physiology: A report from the Pediatric Heart Network Infant Single Ventricle Trial. C. Ravishankar, J Pediatr 2013; 162(2): 250–256.e2.
• Challenges and successes of recruitment in the “angiotensin-converting enzyme inhibition in infants with single ventricle trial” of the Pediatric Heart Network. N. Pike, Cardiol Young 2013; 23(2): 248–257.
• Factors Impacting Growth in Infants with Single Ventricle Physiology: A Report from Pediatric Heart Network Infant Single Ventricle Trial. R. Williams, J Pediatr 2011; 159:1017-22.
• Renin-Angiotensin-Aldosterone Genotype Influences Ventricular Remodeling in Infants with Single Ventricle. S. Mital, Circulation 2011; 123:2353-2362.
• Enalapril in Infants with Single Ventricle: results of a multicenter randomized trial.  D. Hsu, Circulation 2010; 122:333-340.
• Birth Weight and Prematurity in Infants With Single Ventricle Physiology: Pediatric Heart Network Infant Single Ventricle Trial Screened Population. R. Williams, Congenit Heart Dis 2010; 5:96-103.
  Many congenital heart defects are associated with low birth weight and prematurity, but there is little information on birth characteristics of babies with a specific kind of defect, single ventricle physiology. This study compares birth parameters for babies enrolled in the Infant Single Ventricle Trial as compared to the typical US population. Infants with single ventricle had increased rates of preterm birth and low birth weight, and they were more likely to be small for gestational age than the general population.
• Rationale and Design of a Trial of Angiotensin-Converting Enzyme Inhibition in Infants With Single Ventricle. D. Hsu, Am Heart J 2009; 157:37-45.
  Angiotensin-converting enzyme (ACE) inhibitors are medicines that improve heart function in adults with heart failure. Infants with a particular type of congenital heart defect (known as single ventricle) have been shown to have abnormal heart function and poor growth. This study was designed to determine if giving ACE inhibitors to babies with single-ventricles would improve their growth, heart function and development. This article describes the design, the participants and the procedures of this trial.

Single Ventricle (SVR) Publications

• The Impact of the Left Ventricle on Right Ventricular Function and Clinical Outcomes in Infants with Single–Right Ventricle Anomalies up to 14 Months of Age. M.S. Cohen, JASE 2018 Jul; DOI: 10.1016/j.echo.2018.05.003 [IN PRESS]
• Survival to Stage II with Ventricular Dysfunction: Secondary Analysis of the Single Ventricle Reconstruction Trial. E. Jean-St-Michel, Pediatr Cardiol 2018 Jun;39(5):955-966.
• A prognostic tool to predict outcomes in children undergoing the Norwood operation. P. Gupta, J Thorac Cardiovasc Surg 2017 Dec;154(6):2030-2037.e2.
• Encrypted prediction: A hacker’s perspective. T. Karamlou, J Thorac Cardiovasc Surg 2017 Dec;154(6): 2038-2040.
• Development and impact of arrhythmias after the Norwood procedure: A report from the Pediatric Heart Network. M.E. Oster, J Thorac Cardiovasc Surg 2017 Mar;153(3):638-645.e2.
• Association of Digoxin With Interstage Mortality: Results From the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Use Dataset. M. Oster, J Am Heart Assoc 2016; 13;5(1). pii: e002566.
• Intraoperative Steroid Use and Outcomes Following the Norwood Procedure: An Analysis of the Pediatric Heart Network's Public Database. J. Elhoff, Pediatr. Crit. Care Med 2016; 17(1):30-5.
• Heart block following stage 1 palliation of hypoplastic left heart syndrome. D. Mah, J Thorac Cardiovasc Surg 2016; 152(1):189-94.
• The Single Ventricle Reconstruction Trial: The data goes public. S. Bradley, J Thorac Cardiovasc Surg 2016; 152(1):195-6.
• Associations Between Day of Admission and Day of Surgery on Outcome and Resource Utilization in Infants With Hypoplastic Left Heart Syndrome Who Underwent Stage I Palliation (from the Single Ventricle Reconstruction Trial). J. Johnson, Am J Cardiol 2015; 116(8):1263-9. Epub 2015 Jul 29.
• Impact of pre-stage II hemodynamics and pulmonary artery anatomy on 12-month outcome in the Single Ventricle Reconstruction Trial. R. Aiyagari, J Thorac Cardiovasc Surg 2014; 148(4):1467-74
• Variation in Feeding Practices Following the Norwood Procedure. L. Lambert, J Pediatr 2014; 164(2): 237–242.e1.
• Risk factors for prolonged length of stay following stage 2 procedure in the Single-Ventricle Reconstruction Trial. S. Schwartz, J Thorac Cardiovasc Surg 2014; 147(6):1791-8, 1798.e1-4.
• A multi-center study comparing shunt type in the Norwood procedure for single-ventricle lesions: 3-Dimensional echocardiographic analysis. G. Marx, Circ Cardiovasc Imaging 2013; 6(6): 934–942.
• Intervention for re-coarctation in the Single Ventricle Reconstruction Trial: Incidence, risk and outcomes. K. Hill, Circulation 2013; 128(9): 10.1161/CIRCULATIONAHA.112.000488.
• Doppler flow patterns in the right ventricle-to-pulmonary artery shunt and neo-aorta in infants with single right ventricle anomalies - Impact on outcome after initial staged palliations. P. Frommelt, J Am Soc Echocardiogr 2013; 26:521-9.
• Introduction to the Single Ventricle Reconstruction trial. E. Bacha, J Thorac Cardiovasc Surg 2012; 144(4): 880-1. 
• Cause, timing and location of death in the Single Ventricle Reconstruction trial. R. Ohye, J Thorac Cardiovasc Surg 2012; 144:907-14.
• Interstage mortality after the Norwood Procedure: Results of the multicenter Single Ventricle Reconstruction Trial. N. Ghanayem, J Thorac Cardiovasc Surg 2012; 144:896-906.
• Risk factors for hospital morbidity and mortality after the Norwood procedure: A report from the Pediatric Heart Network Single Ventricle Reconstruction Trial. S. Tabbutt, J Thorac Cardiovasc Surg 2012; 144:882-95.
• Variation in perioperative care across centers for infants undergoing the Norwood procedure. S. Pasquali, J Thorac Cardiovasc Surg 2012; 144:915-21.
• A Predictive Model for Neurodevelopmental Outcome Following the Norwood Procedure. W. Mahle, Pediatr Cardiol 2013; 34(2):327-333.
• Does initial shunt type for the Norwood procedure affect echocardiographic measures of cardiac size and function during infancy? The Single Ventricle Reconstruction Trial. P. Frommelt, Circulation 2012; 125:2630-2638.
• Intermediate-term mortality and cardiac transplantation in infants with single-ventricle lesions: Risk factors and their interaction with shunt type. J. Tweddell, J Thorac Cardiovasc Surg 2012; 144(1):152-159.e2.
• Early neurodevelopmental outcome in hypoplastic left heart syndrome and related anomalies: The Single Ventricle Reconstruction Trial. J. Newburger, Circulation 2012; 125:2081-2091.
• Reporting adverse events in a surgical trial for complex congenital heart disease: The Pediatric Heart Network Experience. L. Virzi, J Thorac Cardiovasc Surg 2011; 142(3): 531-537.
• Celiac Artery Flow Pattern in Infants with Single Right Ventricle Following the Norwood Procedure with a Modified Blalock-Taussig or Right Ventricle to Pulmonary Artery Shunt. J. Johnson, Pediatr Cardiol 2011; 32:479-486.
• Prenatal Diagnosis and Risk Factors for Preoperative Death in Neonates with Single Right Ventricle and Systemic Outflow Obstruction: Screening Data from the Pediatric Heart Network Single Ventricle Reconstruction Trial. A. Atz, J Thorac Cardiovasc Surg 2010; 140:1245-1250.
• Comparison of Shunt Types in the Norwood Procedure for Single-Ventricle Lesions. R. Ohye, N Engl J Med 2010; 362(21):1980-1992.
  In children with a single heart ventricle undergoing the Norwood procedure, a trial was conducted to determine if one of two different shunts resulted in better survival after 12 months without the need for a heart transplant. Babies were randomly assigned to receive either the traditional modified Blalock-Taussig shunt (MBTS) or the right ventricle- pulmonary artery (RV-PA) conduit. The study showed that babies who received the RV-PA conduit had better survival without needing a heart transplant 12 months after entering the study. However, when the babies were followed for a longer period of time, there was no difference between the two groups. The results also revealed that babies who received the RV-PA conduit needed more procedures and had more complications than those receiving the MBTS. 
• Design and Rationale of a Randomized Trial Comparing the Blalock-Taussig and Right Ventricle-Pulmonary Artery Shunts in the Norwood Procedure. R. Ohye, J Thorac Cardiovasc Surg 2008; 136:968-975.
  The first of the three surgeries (the Norwood procedure) for babies born with a single heart ventricle is one of the highest risk procedures in congenital heart surgery. Two types of shunts (tubes) may be used for the first surgery: the traditional modified Blalock-Taussig shunt (MBTS) and the right ventricle to pulmonary artery (RV-PA) shunt. Some research has shown one technique to be better than the other, but other research has shown no differences in the outcomes for each technique. This article describes a trial designed by the Pediatric Heart Network to compare the two types of shunts. In the study, babies were randomly assigned to receive either the MBTS or the RV-PA shunt, and they were followed over time to compare the outcomes.
• The Modified Blalock-Taussig Shunt Versus the Right Ventricle-to-Pulmonary Artery Conduit for the Norwood Procedure. R. Ohye, Pediatr Cardiol 2007; 28:122-125.
  Babies born with a single heart ventricle require multiple surgeries in order to provide adequate blood flow to the body. The first of the three surgeries is one of the highest risk procedures in congenital heart surgery. Two types of shunts (tubes) may be used for the first surgery: the traditional modified Blalock-Taussig shunt (MBTS) and the right ventricle to pulmonary artery (RV-PA) shunt. This article explains the advantages and disadvantages of each shunt and the Pediatric Heart Network’s clinical trial to determine if one shunt type is better than another in this population. (see results of the PHN trial)

Single Ventricle Reconstruction Extension Study

• The Impact of the Left Ventricle on Right Ventricular Function and Clinical Outcomes in Infants with Single-Right Ventricle Anomalies up to 14 Months of Age. M.S. Cohen, J Am Soc Echocardiogr. 2018 Jul 3. pii: S0894-7317(18)30249-9.
  We assessed whether left ventricular size and function influence right ventricular function and clinical outcomes after staged palliation for single right ventricle anomalies. In the Single Ventricle Reconstruction (SVR) trial cohort, we studied left ventricle size and function compared to echocardiography-derived measures of right ventricular size and function as well as tricuspid regurgitation. We also assessed the impact of the left ventricle on outcome (death and/or heart transplantation). The hypoplastic left heart syndrome subtype of aortic atresia/mitral atresia was less likely to have a measurable left ventricle compared to other subtypes. Right ventricle end-diastolic and end-systolic volumes were significantly larger, while diastolic indices suggested better properties in those subjects with no measurable left ventricle compared to those with measurable ventricles. Right ventricular ejection fraction and tricuspid regurgitation were not different based on left ventricle size and function. There was no difference between groups in transplantation-free survival up to 14 months of age. In patients with single right ventricle anomalies, left ventricular size and function has a minimal short-term impact on survival and right ventricular performance.
• Heart failure after the Norwood procedure: An analysis of the Single Ventricle Reconstruction Trial. W.T. Mahle, J Heart Lung Transplant. 2018 Jul;37(7):879-885.
  Heart failure is a known complication following the Norwood procedure for single ventricle anomalies. Examination of the Single Ventricle Reconstruction (SVR) trial cohort revealed that almost 15% of participants developed heart failure following discharge from the Norwood procedure. Shunt type had no association with heart failure. The risk for developing heart failure was highest in the first year of life. Over half of the children who developed heart failure were listed for transplant, though a significant number died while awaiting a transplant. Among transplant-free survivors to 6 years of age, fewer than 5% of children with palliated single ventricle congenital heart disease had class IV symptomatic heart failure. Several procedure and patient-related factors were associated with development of heart failure, including impaired right ventricular function after the Norwood procedure.
• Transplant-Free Survival and Interventions at 6 Years in the Single Ventricle Reconstruction Trial. J.W. Newburger, Circulation. 2018 May; 137(21):2246-2253.
  We examined transplant-free survival and other outcomes at 6 years after the Norwood procedure with a right ventricle-to-pulmonary artery shunt (RVPAS) compared to a modified Blalock‒Taussig shunt (MBTS) in children enrolled in the PHN’s Single Ventricle Reconstruction (SVR) trial. The RVPAS group had similar survival without needing a heart transplant at 6 years but required more catheter interventions before the Fontan procedure. After the Fontan procedure, the two shunt groups had similar rates of transplant-free survival and of catheter intervention, as well as similar right heart function, cardiac symptoms, and complications. However, children in both groups had a steady increase in complications over time; by 6 years, 20% had suffered a blood clot, 15% a seizure, and 7.5% a stroke. These data emphasize the importance of close follow-up and the need to find new strategies to improve the long-term outlook for children with single ventricle anomalies.
• Utilisation of early intervention services in young children with hypoplastic left heart syndrome. K. Mussatto, Cardiol Young. 2018; 28(1):126-133.
• Assessment of Growth Six Years after the Norwood Procedure: Results from the Single Ventricle Reconstruction Trial. P. Burch, J. Pediatr. 2017; 180:270-274.e6.
• Factors affecting Fontan length of stay: Results from the Single Ventricle Reconstruction trial. C. Ravishankar, J Thorac Cardiovasc Surg. 2016; 151(3):669-675.
• Impact of Initial Shunt Type on Cardiac Size and Function in Children with Single Right Ventricle Anomalies prior to the Fontan Procedure—The Single Ventricle Reconstruction Extension Trial. P. Frommelt, J Am Coll Cardiol 2014; 64(19):2026-35.
• Longitudinal assessment of growth in hypoplastic left heart syndrome: results from the single ventricle reconstruction trial. P. Burch, J Am Heart Assoc 2014; 3(3):e000079.
• Factors associated with neurodevelopment for children with single ventricle lesions. C. Goldberg, J Pediatr 2014; 165(3): 490-496. 
• Transplantation-free survival and interventions at 3 years in the single ventricle reconstruction trial. J. Newburger, Circulation 2014; 129:2013-2020.

Team 4 Growth Publications

• Passive range of motion exercise to enhance growth in infants following the Norwood procedure: a safety and feasibility trial. L.M. Lambert, Cardiol Young 2017; 27(7):1361-1368.

Udenafil Publications

• Results of a phase I/II multi-center investigation of udenafil in adolescents after fontan palliation. D. Goldberg, Am Heart J. 2017; 188:42-52.