Clinical trial NCT02455531: Long-term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type
Official title: 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)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Heart Defects
Lead sponsor: Carelon Research
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2015-05-28
Enrollment: 264
Sex: ALL
Minimum age (years): 10
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: RV ejection fraction (RVEF) at 11 years, as measured by cardiac magnetic resonance (CMR).
timeFrame: 10 to 12 years of age for each participant (11 years ± 1 year)
Secondary outcomes:
measure: The incidence of death or cardiac transplantation between those randomized to receive a RVPAS vs. a MBTS at the time of the Norwood operation.
timeFrame: 11 years ± 1 year to 16 years
measure: The exercise tolerance between those randomized to a RVPAS vs. a MBTS.
timeFrame: 11 years ± 1 year to 16 years
measure: The incidence of arrhythmias between those randomized to a RVPAS vs. a MBTS.
timeFrame: 11 years ± 1 year to 16 years
measure: The neurodevelopmental outcomes at 11 years of age in those randomized to a RVPAS vs. a MBTS
timeFrame: 11 years ± 1 year
measure: Develop risk stratification models for 1) cardiac outcomes, 2) transplant-free survival, and 3) neurodevelopmental outcomes.
timeFrame: 11 years ± 1 year to 16 years
measure: Collect specimens from subjects and their parents to further develop the biologic specimen repository.
timeFrame: 11 years ± 1 year to 16 years
Other outcomes:
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