This was the second follow-up to the Single Ventricle Reconstruction (SVR) trial which aimed to see which shunt type was best for infants with single ventricle heart defects undergoing the Norwood operation. The study objectives were to determine if shunt type at the time of Norwood operation is associated with long-term differences in cardiac function, survival or contributors to quality of life, and to characterize long-term outcomes and determine risk factors other than shunt type for adverse long-term outcomes in children with hypoplastic left heart syndrome (HLHS) and other related single ventricle anomalies.
~60% of SVR cohort still alive without heart transplant.
on outcomes by 12 years of age.
but exercise performance lower than in children without heart disease and children continued to be at risk for complications.
This was a prospective follow up study of the SVR cohort. Enrollment closed in 2020 with 237 enrolled participants.
This study was a prospective follow-up on an existing cohort of children with HLHS and other single RV anomalies enrolled in early infancy in a randomized clinical trial of Norwood procedure with MBTS versus RVPAS. This cohort last underwent research testing at age 6 (SVRII). Families of surviving SVR participants were contacted and asked to return for multidisciplinary evaluations from ages 10-12 years old. Participants were then assessed annually until age 16 years old for vital status and medical history.
Among 549 participants enrolled in the SVR Trial, 237/313 (76%) transplant-free survivors participated in SVR III. We found that just about 60% of the original group enrolled in the SVR Trial were alive with their original heart, and that, by 12 years, there was no difference in survival between those who received a mBTTS or RVPAS. Heart function as measured by cardiac MRI and by echocardiogram, on average, were mostly in the normal range and there was no difference between the two treatment groups. Bicycle exercise testing did not differ between the treatment groups either, but, on average, the children in our study had exercise performance which was lower than in children without heart disease. We found that children in this study continued to be at some risk for complications, such as arrhythmias, strokes and protein losing enteropathy into adolescence. Although we compared many factors, the only differences we found between the surgical treatment groups (mBTTS vs. RVPAS) was some increase in the risk for protein losing enteropathy and a greater need for catheterization intervention for those who had received a RVPAS compared to those who received a mBTTS.
Since, for the most part, it didn’t seem to matter if a mBTTS or an RVPAS was used at the time of the first operation, we tried to understand the factors that did influence heart function and those that were associated with transplant -free survival, but we were unable to find any treatment approaches which meaningfully predicted outcomes.
We concluded that, by 12 years of age, shunt type had minimal effect on transplant -free survival, heart function, exercise performance, and complication rates. Heart function was preserved in most transplant free survivors. Given sub-optimal transplant-free survival, reduced exercise performance and ongoing risk for complications, innovative strategies to improve long-term outcomes for patients with HLHS are needed.
The PHN is grateful to the children and families who participated in this study.
C. S. Goldberg, MD. American Heart Journal. 2022 Dec; 254:216-227.
The purpose of this paper is to describe the approach to the long-term follow-up of the Single Ventricle Reconstruction (SVR) cohort through the study familiarly known as SVR III. The original SVR trial aimed to understand what type of surgical connection to the pulmonary arteries worked better for infants with hypoplastic left heart syndrome. The individuals enrolled in the SVR trial were then recruited for long-term follow-up, asked to return at 10-12.5 years for an in person evaluation which included cardiac MRI, echocardiogram, exercise testing and neurodevelopmental assessments. Also, every year, through age 16 years, medical history information was collected. Details of each assessment and the medical history form are included in this manuscript. 74% of the eligible cohort, participated in SVR III. Approaches to engaging patients and families in the study and needed adaptations due to participant age and the COVID pandemic are shared.
J. Detterich. Pediatric Cardiology. 2023 Oct; 44(7):1454-1461.
The Single Ventricle Reconstruction Trial was a first-of its kind randomized surgical trial to determine whether a right ventricle to pulmonary artery shunt was advantageous to patients with hypoplastic left heart syndrome as compared to the Blalock-Taussig-Thomas shunt. The third follow up study (SVR III) also advanced our understanding of this unique circulation by using magnetic resonance imaging of the heart. This test is the gold standard for assessing myocardial function and flow through the heart but is thought to be too long and places a high burden on the patient to lie still for adequate imaging without sedation. In this paper we demonstrate that this test is feasible, well-tolerated and provides significantly improved information about our patients’ circulation.
W. T. Mahle. The Journal of heart and lung transplantation. 2024 Mar; 43(3):453-460.
In this study, we wanted to see how many children aged 12 years with hypoplastic left heart syndrome had heart failure. We discovered that a little more than 5% of the children experienced major heart failure events, like needing a heart transplant. The good news is that most of these children survived after getting a transplant. Additionally, just over 10% of the children had noticeable heart failure symptoms, such as feeling tired when they walked one block or more.
C. S. Goldberg. Circulation. 2023 Oct 24; 148(17):1330-1339.
Treatment for children with hypoplastic left heart syndrome (HLHS) includes an operation on the heart in the first days of life and then subsequent procedures later in infancy and in the preschool years. One of the steps of the first procedure is to provide a source of blood flow to the lungs. Between 2005 and 2008, through the Single Ventricle Reconstruction (SVR) Trial, infants with HLHS received either a shunt from a branch of the aorta to the pulmonary arteries, called a modified Blalock-Taussig-Thomas shunt (mBTTS) or a connection from the right ventricle to the pulmonary arteries (RVPAS). Early data suggested that those infants who had the RVPAS had better survival in the first year of life. We continued to follow these infants over time. Through this study, affectionately known as the SVR III study, we aimed to evaluate if longer-term outcomes by early adolescence, including survival without needing a heart transplant, heart function, exercise tolerance and complications such as the risk of arrhythmias, are affected by the way the first operation was performed, with a mBTTS or an RVPAS.
Among 549 participants enrolled in the SVR Trial, 237/313 (76%) transplant-free survivors participated in SVR III. We found that just about 60% of the original group enrolled in the SVR Trial were alive with their original heart, and that, by 12 years, there was no difference in survival between those who received a mBTTS or RVPAS. Heart function as measured by cardiac MRI and by echocardiogram, on average, were mostly in the normal range and there was no difference between the two treatment groups. Bicycle exercise testing did not differ between the treatment groups either, but, on average, the children in our study had exercise performance which was lower than in children without heart disease. We found that children in this study continued to be at some risk for complications, such as arrhythmias, strokes and protein losing enteropathy into adolescence. Although we compared many factors, the only differences we found between the surgical treatment groups (mBTTS vs. RVPAS) was some increase in the risk for protein losing enteropathy and a greater need for catheterization intervention for those who had received a RVPAS compared to those who received a mBTTS.
Since, for the most part, it didn’t seem to matter if a mBTTS or an RVPAS was used at the time of the first operation, we tried to understand the factors that did influence heart function and those that were associated with transplant -free survival, but we were unable to find any treatment approaches which meaningfully predicted outcomes.
We concluded that, by 12 years of age, shunt type had minimal effect on transplant -free survival, heart function, exercise performance, and complication rates. Heart function was preserved in most transplant-free survivors. Given sub-optimal transplant-free survival, reduced exercise performance and ongoing risk for complications, innovative strategies to improve long-term outcomes for patients with HLHS are needed.
V. Schmithorst. Diagnostics (Basel). 2023 Apr 30; 13(9):1604.
Children born with heart disease can be at risk for problems with development and quality of life. We describe a study of children age 10-12 with hypoplastic left heart syndrome who had Fontan surgery and were participating in the Single Ventricle Reconstruction III Study. The goal was to obtain images of the brain and compare them to healthy children (not born with heart disease) and look for associations with mental abilities, behavior, demographics, and medical factors. The study faced some challenges: (1) coordinating brain imaging for participants already undergoing extensive testing in the main study, (2) recruiting healthy participants for comparison, and (3) the COVID-19 pandemic. Challenges were addressed by: (1) adding additional study sites, (2) increasing the frequency of meetings with site coordinators, and (3) using research registries and advertising the study to community-based groups.
T. Miller. Circulation. 2025 Oct 28; 152(17):1246-1261.
This project describes the neurodevelopmental follow-up of the Single Ventricle Reconstruction (SVR) cohort through the study familiarly known as SVR III. The original SVR trial aimed to understand what type of surgical connection to the pulmonary arteries worked better for infants with hypoplastic left heart syndrome. The individuals enrolled in the SVR trial were then recruited for long-term follow-up and were asked to return at 10-14 years for an in person neurodevelopmental evaluation. Those who returned for this evaluation at average age of 11 years overall demonstrated worse scores on tests assessing intellectual functioning, academic achievement, memory, attention, adaptive behavioral functioning, executive functioning, and social, emotional and behavioral functioning compared to the general population. A less complicated medical and surgical history is associated with better neurodevelopmental outcomes, but socioeconomic risk factors at this age have more consistent association with outcomes than medical and surgical risk factors. The findings suggest that patients with single ventricle heart disease should have ongoing assessment of neurodevelopment and psychosocial functioning well into adolescence. Furthermore, addressing disparities in neurodevelopmental and psychosocial outcomes requires consideration of the impact of socioeconomic risk on medical complexity.