Heart Defects
Conditions
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.
Interventions
None listed
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Carelon Research
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
10 Years to 12 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RVEF at 10-12 Years on MRI | assessed between 10-12 years of age, an average of 53.2 days from consent | RV ejection fraction (RVEF) at 10-12 years, as measured by cardiac magnetic resonance (CMR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Exercise Tolerance Between Those Randomized to a RVPAS vs. a MBTS. | 11 years ± 1 year to 16 years | Exercise capacity: Maximal Oxygen Consumption (VO2max), maximal work rate, and anaerobic threshold |
| Atrial and Ventricular Arrhythmias | 11 years ± 1 year to 16 years | The incidence of arrhythmias between those randomized to a RVPAS vs. a MBTS. |
| Death or Cardiac Transplantation | 11 years ± 1 year to 16 years | The incidence of death or cardiac transplantation between those randomized to receive a RVPAS vs. a MBTS at the time of the Norwood operation. |
| Risk Stratification Models | 11 years ± 1 year to 16 years | Develop risk stratification models for 1) cardiac outcomes, 2) transplant-free survival, and 3) neurodevelopmental outcomes. |
| Biospecimens | 11 years ± 1 year to 16 years | Collect specimens from subjects and their parents to further develop the biologic specimen repository. |
| The Neurodevelopmental Outcomes at 11 Years of Age in Those Randomized to a RVPAS vs. a MBTS | 11 years ± 1 year | Achievement, as measured by the Wechsler Individual Achievement Tests (WIAT) (Math and Reading); Intelligence, as measured by the Wechsler Intelligence Scale for Children (WISC); Other domains of neurodevelopmental function including assessment of language, executive function, visual spatial skills, motor function, memory, social skills, behavior, health-related quality of life (HRQoL) and adaptive function. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| mBTTS Blalock Taussig Thomas shunt at Norwood | 109 |
| RVPAS right-ventricular-to-pulmonary-artery shunt at Norwood | 128 |
| Total | 237 |
Baseline characteristics
| Characteristic | mBTTS | RVPAS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 109 Participants | 128 Participants | 237 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 27 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants | 100 Participants | 195 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Non-White | 13 Participants | 21 Participants | 34 Participants |
| Race/Ethnicity, Customized White | 95 Participants | 106 Participants | 201 Participants |
| Sex: Female, Male Female | 47 Participants | 46 Participants | 93 Participants |
| Sex: Female, Male Male | 62 Participants | 82 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 109 | 3 / 128 |
| other Total, other adverse events | 0 / 109 | 0 / 128 |
| serious Total, serious adverse events | 0 / 109 | 0 / 128 |
Outcome results
Primary
RVEF at 10-12 Years on MRI
RV ejection fraction (RVEF) at 10-12 years, as measured by cardiac magnetic resonance (CMR).
Time frame: assessed between 10-12 years of age, an average of 53.2 days from consent
Population: participants who underwent cardiac MRI
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| mBTTS | RVEF at 10-12 Years on MRI | 52 percentage of blood pumped | Standard Deviation 7.4 |
| RVPAS | RVEF at 10-12 Years on MRI | 51 percentage of blood pumped | Standard Deviation 9.6 |
Secondary
Atrial and Ventricular Arrhythmias
The incidence of arrhythmias between those randomized to a RVPAS vs. a MBTS.
Time frame: 11 years ± 1 year to 16 years
Secondary
Biospecimens
Collect specimens from subjects and their parents to further develop the biologic specimen repository.
Time frame: 11 years ± 1 year to 16 years
Secondary
Death or Cardiac Transplantation
The incidence of death or cardiac transplantation between those randomized to receive a RVPAS vs. a MBTS at the time of the Norwood operation.
Time frame: 11 years ± 1 year to 16 years
Secondary
Risk Stratification Models
Develop risk stratification models for 1) cardiac outcomes, 2) transplant-free survival, and 3) neurodevelopmental outcomes.
Time frame: 11 years ± 1 year to 16 years
Secondary
The Exercise Tolerance Between Those Randomized to a RVPAS vs. a MBTS.
Exercise capacity: Maximal Oxygen Consumption (VO2max), maximal work rate, and anaerobic threshold
Time frame: 11 years ± 1 year to 16 years
Secondary
The Neurodevelopmental Outcomes at 11 Years of Age in Those Randomized to a RVPAS vs. a MBTS
Achievement, as measured by the Wechsler Individual Achievement Tests (WIAT) (Math and Reading); Intelligence, as measured by the Wechsler Intelligence Scale for Children (WISC); Other domains of neurodevelopmental function including assessment of language, executive function, visual spatial skills, motor function, memory, social skills, behavior, health-related quality of life (HRQoL) and adaptive function.
Time frame: 11 years ± 1 year