Long-term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type (SVRIII)

Long-term Outcomes of Children With HLHS (Hypoplastic Left Heart Syndrome) and the Impact of Norwood Shunt Type (A Study Conducted by the Pediatric Heart Network)

The purpose of this study is to compare direct and indirect measures of right ventricular (RV) systolic and diastolic function between 11 year old subjects who had been randomly assigned to receive a right ventricle to pulmonary artery shunt (RVPAS) vs. a modified Blalock-Taussig shunt (MBTS) at the time of the Norwood operation.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Defects

Detailed Description

The Single Ventricle Reconstruction (SVR) trial was the first multicenter, randomized clinical trial to compare two operations in the field of congenital heart disease.8,11 Children with HLHS and other related single RV lesions were enrolled and randomized to receive either a MBTS or a RVPAS at the time of the initial Norwood procedure. This landmark study provided extraordinary insight not only into the consequences of both shunt types, but also into the course, treatment responses and short- and mid-term outcomes for these medically complex patients. Through the SVR Trial and SVR Extension Study (SVR II), outcomes, including but not limited to the primary outcome of transplant-free survival, have now been evaluated in this patient cohort when the last enrolled patient reached 12 months and again at 3 years of age. While early post-operative transplant-free survival during the interstage period7 and at one year8 was better for those children randomized to a RVPAS, survival by the 3-year evaluation appeared equivalent between the two shunt types. Moreover, RVEF was somewhat diminished and the number of interventions was higher in the RVPAS group.12 These findings raised concern that the RV dysfunction in the RVPAS group may be progressive, leading to significantly worse long-term outcomes; if so, the benefits of the RVPAS for short-term survival may be outweighed by longer-term morbidity and mortality. Thus, the optimal surgical approach for newborns with HLHS and related single RV lesions remains unclear.

The Pediatric Heart Network (PHN) Investigators have a unique opportunity and responsibility to analyze the effect of the type of systemic-to-pulmonary artery shunt placed during the Norwood procedure on longer-term survival, as well as to define its effect on other long-term outcomes in this multi-institutional cohort of exquisitely characterized subjects with single RV lesions. As subjects enrolled in the SVR cohort approach a decade of age, the investigators aim: 1) to determine if shunt type at the time of Norwood operation is associated with any long-term differences in cardiac function, survival, or contributors to quality of life; and 2) to characterize long-term outcomes and determine risk factors other than shunt type for adverse long-term outcomes in children with HLHS and other related single ventricle anomalies.

• Study Type: Observational
• Enrollment (Actual): 264

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 12 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

All SVR study cohort members will be contacted to assess for vital status. Transplant free survivors will be approached to participate in the in-person assessment.

Description

Inclusion Criteria:

• All SVR study cohort members will be contacted to assess for vital status. Transplant free survivors will be approached to participate in the in-person assessment.

Exclusion Criteria:

• Patients who have undergone cardiac transplantation or biventricular conversion from all outcomes other than vital status.
• Those with pacemakers will be excluded from the CMR, and patients <130 cm in height will be excluded from the exercise test.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Transplant-free survivors; Transplant-free survivors of the SVR cohort (All SVR survivors are eligible to be followed for vital status.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
RV ejection fraction (RVEF) at 11 years, as measured by cardiac magnetic resonance (CMR).	10 to 12 years of age for each participant (11 years ± 1 year)

Secondary Outcome Measures

Outcome Measure	Time Frame
The incidence of death or cardiac transplantation between those randomized to receive a RVPAS vs. a MBTS at the time of the Norwood operation.	11 years ± 1 year to 16 years
The exercise tolerance between those randomized to a RVPAS vs. a MBTS.	11 years ± 1 year to 16 years
The incidence of arrhythmias between those randomized to a RVPAS vs. a MBTS.	11 years ± 1 year to 16 years
The neurodevelopmental outcomes at 11 years of age in those randomized to a RVPAS vs. a MBTS	11 years ± 1 year
Develop risk stratification models for 1) cardiac outcomes, 2) transplant-free survival, and 3) neurodevelopmental outcomes.	11 years ± 1 year to 16 years
Collect specimens from subjects and their parents to further develop the biologic specimen repository.	11 years ± 1 year to 16 years

Collaborators and Investigators

• Sponsor: Carelon Research
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): October 1, 2020
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: May 22, 2015
• First Submitted That Met QC Criteria: May 26, 2015
• First Posted (Estimated): May 28, 2015

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Hypoplastic Left Heart Syndrome
• Other Study ID Numbers: U10HL068270-4b; U10HL068270 (U.S. NIH Grant/Contract)