Since 2001, the Pediatric Heart Network has published and presented over 150 manuscripts, 85 abstracts, and 75 posters/presentations. This is a complete listing of all manuscripts, categorized by study.
W. Lai, Am Heart J 2011; 161:13-67.
J. Kaltman, Circulation 2010; 121:2766-72.
L. Mahony, Pediatr Cardiol 2006; 27:191-198.
W. T. Mahle, Pediatr Crit Care Med; 2016 Oct;17(10):939-947.
This study compared how well babies did after surgery, for Tetralogy of Fallot or coarctation of the aorta, at research sites where babies were removed from the ventilator early (called early extubation) versus at research sites where babies were not taken off the ventilators early. The clinical practice guideline used at the intervention sites significantly increased the rate of early extubation with no change in the rate of reintubation or postoperative ICU length of stay.
M. J. Wolf, Am Heart J; 2016 Apr;174:129-37.
This paper describes how collaborative learning was used to develop a clinical practice guideline to design a study examining early extubation of babies after heart surgery.
K. E. McHugh, Ann Thorac Surg. 2019 May;107(5):1421-1426.
A. F. Zuppa, Br J Anaesth. 2019 Dec;123(6):839-852.
L. Lopez, Circ Cardiovasc Imaging 2017; 10(11):e006979.
Data were collected on 3566 healthy nonobese children ≤18 years of age with normal echocardiograms to produce reference values for echocardiogram measurements based on age, sex, race, ethnicity, height and weight. Body size was found to be the best predictor of the sizes of cardiovascular structures, and age, sex, and race did not have a clinically significant effect on this relationship.
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.
P. C. Frommelt, J Am Soc Echocardiogr. 2019 Oct;32(10):1331-1338.e1.
D. Truong, Cardiol Young. 2020 Apr;30(4):456-461.
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.
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.
A. Ostrow, Ann Thorac Surg 2006; 82:695-700.
K. Sundareswaran, Ann Thorac Surg 2006; 82(4):1267-75; discussion 1275-77.
D. de Zélicourt, J Thorac Cardiovasc Surg 2006; 131:785-91.
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.
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.
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.
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.
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.
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.
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.
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.
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.
K. K. Whitehead, J Thorac Cardiovasc Surg. 2009 Jul; 138(1): 96–102.
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.
M. Cohen, Am Heart J 2010; 160:1092-1098.e1.
P. Anderson, Pediatr Cardiol 2010; 31(8): 1219–1228.
A. Prakash, Am J Cardiol 2010; 106(11):1652-6.
E. Stephenson, J Am Coll Cardiol 2010; 56:890-6.
J. R. Darst, Cardiol Young. 2010 Dec; 20(6): 593–601.
J. Rhodes, J Am Soc Echocardiogr 2011; 24:1213-9.
P. Banka, Am Heart J 2011; 162:125-130.
A. Atz, J Am Coll Cardiol 2011; 57:2437-43.
A. Atz, Congenit Heart Dis 2011; 6:313-321.
R. Williams, Echocardiography 2013; 30:1098-1106.
A. Atz, Cardiol Young 2013; 23(3): 335–343.
R. Williams, Congenit Heart Dis 2013;8(1): 32–39.
P. Madan, Am Heart J. 2013 Aug;166(2):365-372.e1.
B. McCrindle, Cardiol Young 2014; 24(3): 469–477.
A. R. Opotowsky, Am J Physiol Heart Circ Physiol. 2014 Jul 1;307(1):H110-7.
R. Margossian, J Am Soc Echocardiogr 2016 Nov;29(11):1066-1073.
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.
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.
A. Atz, Congenit Heart Dis 2015; 10(1):E30-42.
B. McCrindle, Pediatr Cardiol 2014; 35(4):632-640.
K. Uzark, J Pediatr 2016; 170:166-172 Epub 2015 Dec 10.
A. Atz, J Am Coll Cardiol 2017; 69(22):2735-2744.
L. M. Lambert, Am Heart J. 2020 Jun;224:192-200. doi: 10.1016/j.ahj.2020.03.022.
D. J. Goldberg, Pediatr Cardiol. 2020 Sep 25. doi: 10.1007/s00246-020-02465-1.
D.J. Goldberg, Am Heart J. 2018 Jul; 201:1-8.
This manuscript describes the design of the Fontan Udenafil Exercise Longitudinal (FUEL) trial. It is a trial comparing udenafil to placebo in children and adolescents with single ventricle heart disease who have undergone the Fontan operation. This study will examine changes in exercise capacity, heart performance, and vascular function. These outcomes are important in understanding whether udenafil may be a beneficial medication to maintain health for a longer period in this population.
D.J. Goldberg, Circulation. 2020 Feb 25;141(8):641-651.
D. Hsu, Circulation 2010; 122:333-340.
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.
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.
S. Mital, Circulation 2011; 123:2353-2362.
R. Williams, J Pediatr 2011; 159:1017-22.
N. Pike, Cardiol Young 2013; 23(2): 248–257.
C. Ravishankar, J Pediatr 2013; 162(2): 250–256.e2.
J. Cnota, J Thorac Cardiovasc Surg 2013; 145(5): 1288–1296.
I. Williams, Am Heart J 2013; 165(4):544-550.e1.
A. S. Carey, Circ Cardiovasc Genet. 2013 Oct; 6(5): 444–451.
R. Butts, Pediatr Cardiol 2014; 35(5):879-87.
J. W. Gaynor, J Thorac Cardiovasc Surg. 2014 Dec;148(6):2560-6.
J. Gaynor, Pediatrics 2015; 135(5):816-25.
T. Miller, J Pediatr 2016; 168:220-225.
R. Margossian, J Am Soc Echocardiogr 2017; 130(7):699-707.e1.
V. Zak, Cardiol Young 2017; 27(7):1265-1270.
S. K. Pasquali, Cardiol Young. 2019 Sep;29(9):1121-1126.
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.
J. Newburger, N Engl J Med 2007; 356(26):2748.
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.
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.
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.
B. Printz, J Am Coll Cardiol 2011; 57:86-92.
L. Sleeper, J Pediatr 2011; 158:831-5.
R. Margossian, J Am Soc Echocardiogr 2011; 24(1):53-9.
R. Lacro, N Engl J Med 2014; 371:2061-2071.
Among 608 children and young adults with Marfan’s syndrome (ages 6 months to 26 years) who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. Aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups.
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.
E. Selamet Tierney, J Am Soc Echocardiogr 2013; 26(6):657-666.
This study describes the characteristics of the echocardiograms for subjects enrolled in the clinical trial. Even when different doctors reviewed and measured the aortas and heart structures of the trial participants, there was excellent agreement in the measurements. Having good agreement is important for accurately reporting the results of the clinical trial.
R. Lacro, Am Heart J 2013; 165:828-835.e3.
This paper describes the population that was screened and then enrolled in the clinical trial. The average age at study entry was 11.2 years, 60% were male, and 25% were older teenagers and young adults. Aortic root diameter z-score was 4.0 and wasn’t different by age. Mitral valve prolapse and mitral regurgitation were more common in females. 56% had a family member with aortic surgery and 32% had a family member with a history of aortic dissection.
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.
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.
D. Y. Mah, Am J Cardiol. 2018 Jul 17. pii: S0002-9149(18)31424-3. doi: 10.1016/j.amjcard.2018.07.006.
J. C. Handisides, J Pediatr. 2019 Jan;204:250-255.e1. doi: 10.1016/j.jpeds.2018.08.061.
S. Driest, J Pediatr. 2020 Jul;222:213-220.e5. doi: 10.1016/j.jpeds.2020.03.064.
M. S. Hamstra, Clin Trials 2020 Aug 21;1740774520945988. doi: 10.1177/1740774520945988.
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.
J. Li, Am Heart J 2011; 161:233-40.
The Pediatric Heart Network designed a placebo-controlled randomized trial to test the effect of enalapril on the amount of left heart valve regurgitation after atrioventricular septal defect (AVSD) repair. Prior to the launch of the trial, a feasibility study was performed to estimate the number of patients with at least moderate mitral regurgitation following AVSD repair. The study was subsequently terminated due to low patient accrual. Several factors led to the problems with enrolling patients: 1) the feasibility study used chart review to assess for valve regurgitation but the trial used echocardiography measurements; 2) clinicians and referring physicians were already believing that enalapril was a good drug to give and many patients eligible for the study were already taking the drug; 3) the echocardiography methods used were developed in adult populations and not children; 4) there are no good data to define the natural history of the disease process.
A. Atz, J Thorac Cardiovasc Surg 2011; 141:1371-9.
This study evaluated contemporary results after repair of a complete atrioventricular septal defect (AVSD) and to determine factors associated with poorer outcomes. Particular attention was paid to type of surgical repair, age at surgery, and presence of Trisomy 21. The type of surgical repair and having Trisomy 21 did not increase the risk of death or serious medical problems. Mortality and morbidity were low. Age at repair ≤2.5 months and need for concurrent surgical procedures were not associated with residual defects or degree of heart valve regurgitation, but were associated with higher resource utilization.
A. Kaza, Ann Thorac Surg 2011;92:1468-75.
Atrioventricular septal defects (AVSD) include abnormalities involving the walls between the heart chambers (atrial and ventricular septa) and the heart valves. The investigators compared patient characteristics, resource utilization, center differences, and outcomes among different types of AVSD. Survival in the current era is excellent, with few residual defects after surgical repair for all AVSD subtypes. Repair of the valves failed to decrease moderate or severe valve regurgitation at the 6-month follow-up. Being older when the heart is repaired increases the risk of moderate or severe valve regurgitation.
A. Prakash, Pediatr Cardiol 2012; 33:205-214.
It is difficult to quantify the amount of regurgitation from the mitral valve using echocardiography. Since children who have an atrioventricular septal defect repaired continue to have varying amounts of mitral regurgitation, the accuracy of proposed echocardiographic methods was proposed to evaluate the severity of the regurgitation. No method performed well. No method proved to be better than the echocardiographer’s subjective assessment of the size of the color Doppler jet and surrounding structures. Reliable assessment of mitral regurgitation remains challenging in this population.
L.M. Lambert, Cardiol Young 2017; 27(7):1361-1368.
This non-randomized pilot study enrolled 20 neonates after surgery for heart repair. The aim was to evaluate the safety and feasibility of a passive range of motion exercise program, administered by trained physical therapists for up to 21 days or until hospital discharge. We found the exercise program to be safe for babies with complex congenital heart disease after surgery and feasible to perform.
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.
M. Nathan, Ann Thorac Surg 2016 Oct 7. pii: S0003-4975(16)30916-X.
The purpose of this study was to assess the accuracy of heart surgery data obtained from a registry compared with data copied from babies’ medical charts by research coordinators. Most PHN sites participate in a registry called “the Society of Thoracic Surgeons- Congenital Heart Surgery Database” in which each site collects data around the time of surgeries. For a select set of variables (like blood pressure, length of hospital stay etc), we found that 94.7% of data elements were both complete and accurate within the registry, suggesting that registry data can be an efficient source for research studies.
M. Nathan, J Thorac Cardiovasc Surg 2019 Nov 15. pii: S0022-5223(19)32761-8.
Outcomes after surgery for congenital heart disease may be impacted by a wide variety of variables. Risk for adverse outcomes begins before surgery and includes innate characteristics such as birth weight, gestational age, genetic abnormalities, and complexity of congenital heart disease (CHD), as well as factors such as hemodynamic stability, adequacy of diagnostic evaluation, prior cardiac operation(s), and appropriateness of surgical plan. Intraoperative risk factors relate to cardiopulmonary bypass, surgical technique, adequacy of intraoperative imaging, subsequent decision to return (or not) to bypass for residual lesions identified, and early post-bypass hemodynamic management. The postoperative milieu may also contribute to outcomes, particularly through serious medical events and complications. The presence of residual lesions (intended or unintended postoperative structural cardiac abnormalities, including those persisting from the preoperative state or newly acquired consequent to the surgical procedure) may be among the most important factors in determining long-term clinical outcomes and costs. The “Residual Lesion Score” (RLS) is a novel tool for evaluating the status of repair across operations and centers. The prospective multi-center RLS study, funded by the National Heart Lung and Blood Institute’s Pediatric Heart Network (PHN), seeks to validate the association of the RLS with early and mid-term postoperative outcomes for common congenital cardiac operations in a multicenter environment. The RLS can serve as an instrument for quality improvement and support future research on perioperative strategies to improve outcomes of congenital heart surgery.
C. J. Prospero, Cardiol Young. 2019 Jul;29(7):930-938.
B. R. Anderson, Cardiol Young. 2020 Jun;30(6):807-817.
R. M. Payne, Am Heart J. 2019 Nov;217:52-63.
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.
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.
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).
A. Atz, J Thorac Cardiovasc Surg 2010; 140:1245-1250.
J. Johnson, Pediatr Cardiol 2011; 32:479-486.
L. Virzi, J Thorac Cardiovasc Surg 2011; 142(3): 531-537.
J. Newburger, Circulation 2012; 125:2081-2091.
J. Tweddell, J Thorac Cardiovasc Surg 2012; 144(1):152-159.e2.
P. Frommelt, Circulation 2012; 125:2630-2638.
S. Pasquali, J Thorac Cardiovasc Surg 2012; 144:915-21.
S. Tabbutt, J Thorac Cardiovasc Surg 2012; 144:882-95.
N. Ghanayem, J Thorac Cardiovasc Surg 2012; 144:896-906.
R. Ohye, J Thorac Cardiovasc Surg 2012; 144:907-14.
E. Bacha, J Thorac Cardiovasc Surg 2012; 144(4): 880-1.
W. Mahle, Pediatr Cardiol 2013; 34(2):327-333.
P. Frommelt, J Am Soc Echocardiogr 2013; 26:521-9.
K. Hill, Circulation 2013; 128(9): 10.1161/CIRCULATIONAHA.112.000488.
G. Marx, Circ Cardiovasc Imaging 2013; 6(6): 934–942.
S. Schwartz, J Thorac Cardiovasc Surg 2014; 147(6):1791-8, 1798.e1-4.
L. Lambert, J Pediatr 2014; 164(2): 237–242.e1.
M. Nathan, J Thorac Cardiovasc Surg. 2014 Nov;148(5):2208-13, 2214.e1-6.
R. Aiyagari, J Thorac Cardiovasc Surg 2014; 148(4):1467-74
J. Johnson, Am J Cardiol 2015; 116(8):1263-9.
G. D. Hill, J Am Soc Echocardiogr. 2015 May; 28(5): 517–521.
S. Bradley, J Thorac Cardiovasc Surg 2016; 152(1):195-6.
D. Mah, J Thorac Cardiovasc Surg 2016; 152(1):189-94.
J. Elhoff, Pediatr. Crit. Care Med 2016; 17(1):30-5.
M. Oster, J Am Heart Assoc 2016; 13;5(1). pii: e002566.
International Cardiac Collaborative on Neurodevelopmental (ICCON) Investigators. Ann Thorac Surg. 2016; 102(3):843-849.
A. Kulkarni. J Heart Lung Transplant. 2016 Mar;35(3):306-311.
K. E. McHugh. Cardiol Young. 2016 Oct;26(7):1303-9.
R. Ramroop, J Thorac Cardiovasc Surg. 2017; 154(5):1703-1710.e3.
M.E. Oster, J Thorac Cardiovasc Surg 2017 Mar;153(3):638-645.e2.
T. Karamlou, J Thorac Cardiovasc Surg 2017 Dec;154(6): 2038-2040.
P. Gupta, J Thorac Cardiovasc Surg 2017 Dec;154(6):2030-2037.e2.
J. M. Meza, Circulation. 2017 Oct 31; 136(18): 1737–1748.
K. E. McHugh, Ann Thorac Surg. 2018 Mar; 105(3): 851–856.
E. Jean-St-Michel, Pediatr Cardiol 2018 Jun;39(5):955-966.
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.
K. R. Wolfe, Pediatr Pulmonol. 2019 Jun;54(6):922-927.
J. Newburger, Circulation 2014; 129:2013-2020.
In the Single Ventricle Reconstruction (SVR) trial, 1-year transplant-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt (MBTS). At 3 years, we compared transplantation-free survival, echocardiographic right ventricular ejection fraction, and unplanned interventions in the treatment groups. By 3 years, the Norwood procedure with RVPAS compared with MBTS was no longer associated with better transplant-free survival. Moreover, RVPAS subjects had slightly worse right ventricular ejection fraction and underwent more catheter interventions.
C. Goldberg, J Pediatr 2014; 165(3): 490-496.
This study measured neurodevelopment at 3 years of age and compared it to neurodevelopment at 14 months of age in children enrolled in the Single Ventricle Reconstruction trial. Scores on tests to evaluate neurodevelopment were lower at 3 years of age when compared to a normal population. The results suggest that even when 14-month scores are within the normal range, children with single ventricle heart defects may be at risk for developmental impairment at pre-school age and beyond. Therefore, all children with HLHS and related single ventricle malformations should be followed longitudinally to improve recognition of delays and potential for intervention.
P. Burch, J Am Heart Assoc 2014; 3(3):e000079.
Poor growth is associated with poor prognosis in several disease processes. While children with single ventricle heart disease are known to be smaller than their peers at birth, there is limited information regarding growth and development in survivors. In this paper we show that single ventricle survivors continue to grow poorly with regards to both height and weight through the first two surgical palliations and at three years of age.
P. Frommelt, J Am Coll Cardiol 2014; 64(19):2026-35.
The initial shunt type at the Norwood procedure used to supply blood flow to the lungs in infants with single right ventricle anomalies may influence heart muscle function during the second and third years of life. This study tested heart muscle function in children in the SVR trial, comparing those who had a right ventricle-to-pulmonary artery shunt versus the modified Blalock-Taussig shunt. While there were no differences between the groups, a markedly enlarged heart, poor heart muscle function, and significant heart valve enlargement/dysfunction at 14 months of age was associated with poorer survival to the Fontan operation.
C. Ravishankar, J Thorac Cardiovasc Surg. 2016; 151(3):669-675.
In the Single Ventricle Reconstruction trial, infants with hypoplastic left heart syndrome (HLHS) who received a right-ventricle-to-pulmonary-artery shunt (RVPAS) versus a modified Blalock-Taussig shunt (MBTS) had lower early postoperative mortality, but more complications at 14 months. This study explored the effect of shunt type and other patient, medical, and surgical factors on postoperative length of stay (LOS) after the Fontan operation. The type of shunt received at the Norwood surgery did not affect how long a baby stayed in the hospital for the Fontan surgery. Rather, more medical complications before the operation resulted in longer LOS after the Fontan operation.
A. W. Eckhauser, Cardiol Young. 2019 Dec;29(12):1510-1516.
P. Burch, J. Pediatr. 2017; 180:270-274.e6.
There is limited information regarding the long-term growth and development in survivors with single ventricle heart disease. This paper assesses growth in these patients after their final palliative surgery until they are school age. These children continue to grow poorly with regards to both height and weight with height being affected to a greater extent than weight.
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.
K. Mussatto, Cardiol Young. 2018; 28(1):126-133.
Children with hypoplastic left heart syndrome are at a risk for neurodevelopmental delays. This study looked at the types of early intervention services (e.g. speech, occupational, physical therapy) and how frequently services were used from age 1 to 4 years in children who participated in the SVR trial. Significant delay was reported by parents in 18-43% of children at ages 3 and 4. More than half of the children (52-69%) were not receiving services at any age and 20-32% were receiving two or more therapies each year. Despite significant neurodevelopmental delays, early intervention service utilization was low in this group of children.
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 interventions, 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.
P. C. Frommelt, Circ Cardiovasc Imaging. 2019 Feb; 12(2): e007865.
T. A. Miller, Pediatrics. 2019 May; 143(5): e20182577.
C. S. Goldberg, Pediatrics. 2019 Nov; 144(5): e20191010.
D. Goldberg, Am Heart J. 2017; 188:42-52.
The purpose of this study was to identify a safe dose of udenafil in teens with single ventricle heart disease. The participants were assigned to placebo or once-a-day or twice-a-day dosing, at different strengths. The 87.5 mg twice-a-day dosing regimen was well tolerated and showed the most consistent drug levels in the blood. This dose was used for the phase III FUEL (Fontan Udenafil Exercise Longitudinal) clinical trial.
S. Colan, J Am Soc Echocardiogr 2012; 25:842-54.
C. Lee, Pediatr Cardiol 2014; 35(4):658-67.
K. Molina, Circ Heart Fail 2013; 6(6): 1214–1222.
R. Margossian, J Am Soc Echocardiogr 2015; 28(5):549-558.
S. Reddy, Pediatr Res. 2015 Feb; 77(2): 363–369.
M. K. Friedberg, J Appl Physiol 2016; 120(11):1301-1318.
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.
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.