HLHS and Norwood Shunt

Principal Investigator: Lois Minich
Keywords: Heart , Cardiology , Norwood , Shunt , HLHS Department: Pediatric Administration
IRB Number: 00081278 Co Investigator:  
Specialty: Pediatric Cardiology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Michelle Robinson
michelle.robinson@hsc.utah.edu
801-213-7639

Brief Summary

Primary Aim:

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 ventricular-to-pulmonary artery shunt (RVPAS) vs. a modified Blalock-Taussig shunt (MBTS) at the time of the Norwood operation.

Hypothesis: Assignment to the RVPAS compared to the MBTS will be associated with worse RV performance in subjects at age 11 years.

Primary Outcome: RV ejection fraction (RVEF) at 11 years, as measured by cardiac magnetic resonance (CMR).

Secondary Outcomes: Secondary outcomes will include additional measures of ventricular systolic, diastolic, and global function by CMR and echocardiogram (echo); anatomic measures related to RV function; and physiologic measures affecting RV function. Secondary outcomes of the greatest importance include:

  • RVEF (measured by echo)
  • RV fractional area change (measured by echo and CMR)
  • Cardiac output (measured by CMR)

Secondary Aims

Secondary Aim 1: To compare the long-term effect of the RVPAS to that of the MBTS on the incidence of death or cardiac transplantation in children with hypoplastic left heart syndrome (HLHS) and other single RV anomalies undergoing the Norwood procedure.

Hypothesis: The incidence of death or cardiac transplant will be higher in the RVPAS group compared to the MBTS group.

Outcomes:

  • The composite of the earliest occurrence of mortality and cardiac transplantation using all available follow-up (ranging from 10 to 15 years).
  • Conditional freedom from death or cardiac transplantation by 11 years among subjects who survived >1 year post-randomization.
  • Survival at 11 years post-randomization and when the last enrolled subject is 11 years old.
  • Transplant at 11 years post-randomization and when the last enrolled subject is 11 years old.
  • The composite of the earliest occurrence of mortality, cardiac transplantation and pacemaker placement, using all available follow-up (ranging from 10-15 years).

 

Secondary Aim 2: To compare exercise tolerance between those randomized to receive a RVPAS vs. a MBTS at the time of the Norwood operation.

Hypothesis: Subjects assigned to the RVPAS group will have lower exercise performance at age 11 years compared to those assigned to the MBTS group.

Outcomes:

  • Exercise capacity: Maximal Oxygen Consumption (VO2max), maximal work rate, and anaerobic threshold

 

Secondary Aim 3: To compare the incidence of arrhythmias between those randomized to receive a RVPAS vs. a MBTS at the time of the Norwood operation.

Hypothesis: The RVPAS will be associated with a greater prevalence of ventricular arrhythmias, but will not differ from the MBTS in the prevalence of atrial arrhythmias.

Outcomes:

  • History of ventricular arrhythmias by age 11 years by parent report and with medical record confirmation.
  • History of atrial arrhythmia by age 11 years, including intra-atrial reentrant tachycardia (IART) or supraventricular tachycardia (SVT), by parent report and with medical record confirmation.

 

Secondary Aim 4: To compare neurodevelopmental outcomes at 11 years of age in subjects randomized to a RVPAS vs. MBTS at the time of the Norwood operation.

Hypothesis: Impaired neurodevelopment will not be associated with Norwood shunt type but mean scores will be lower in single ventricle patients compared to the normative population.

Outcomes:

  • 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.

 

Secondary Aim 5: To develop risk stratification models for the following classes of long term outcomes: 1) cardiac outcomes, 2) transplant-free survival, and 3) neurodevelopmental outcomes.

Hypothesis: Long-term outcomes at 11 years will be worse for participants with a higher frequency of medical events.

Analyses for this aim will:

  • Provide information about the association of events and interventions other than the randomized surgical procedure with late outcomes.
  • Identify early cardiac and neurodevelopmental surrogate endpoints that might be useful in future studies of management strategies.
  • Determine if correlates of long-term outcomes vary according to patient subgroup factors.

Secondary Aim 6: To collect specimens from subjects with HLHS and other single RV anomalies and their parents in whom DNA samples either were not collected previously or are of insufficient quality or quantity,  to further develop the biologic specimen repository (biorepository).

Purpose: To build on the collection of genetic and other biologic material from the SVR cohort, to leverage the careful phenotyping of the SVR cohort to provide an opportunity for future phenotype-genotype studies and to make samples available for future hypothesis-driven  studies aimed at identifying molecular markers and genetic determinants of outcome in HLHS and related single RV  lesions.

 Ancillary Study Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes, Tier 2 Site 

The proposed ancillary study will leverage the ongoing NHLBI-funded Single Ventricle Reconstruction Study by using innovative graph measures of brain connectivity to elucidate how alterations of the “connectome” in children with critical congenital heart disease are associated with developmental disabilities and their associated clinical risk factors.  Improved understanding of these interrelationships may facilitate development of targeted interventions to improve outcome in the soaring population of adult Fontan survivors.

We will use linear regression and mediation statistical methods to analyze associations of MRI graph measures with SVRIII neurodevelopmental measures and surgical/non-surgical clinical independent risk factors.  Upon successful completion, these studies will elucidate the nature and basis of neurodevelopmental disability in single ventricle patients following Fontan palliation. This research will also contribute a novel and robust set of clinical/research tools in the form of neuroimaging biomarkers that can be used to help classify and predict outcomes in complex CHD.

Specific Aim 1:    To characterize the global brain network topology of the SVR III cohort;

Specific Aim 2:    To determine which neurocognitive and behavioral outcomes predict global brain network topology in the SVR III cohort;

Specific Aim 3:    To determine which patient factors (e.g., birth weight, gestational age, and maternal education) and medical factors (e.g., intraoperative conduct during Norwood procedure, hemodynamic complications, types and number of interventions, and measures of global morbidity) predict global brain network topology in the SVRIII cohort; and

Specific Aim 4:    To precisely characterize the specific relationships between global brain network topology, specific patient/medical factors, and adverse neurocognitive/behavioral outcomes in the SVR III cohort.

The study sites will be divided into tier 1 and tier 2. The tier 1 sites will recruit both SVR III subjects and healthy controls. The tier 2 sites will only recruit SVR III subjects.

 

Inclusion Criteria

Subject Inclusion:

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.

The biological parents will be asked to participate in the study to provide a DNA sample if they consent.

Ancillary Study: Single Ventricle Reconstruction III:  Brain Connectome and Neurodevelopmental Outcomes, Tier 2 Site

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

Subject Exclusion:

We will exclude 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 unable to comfortably reach the exercise bike petals enough to effectively pedal the cycle ergometer will be excluded from the exercise test..

 

Ancillary Study: Single Ventricle Reconstruction III:  Brain Connectome and Neurodevelopmental Outcomes, Tier 2 Site

We will exclude patients who have undergone cardiac transplantation or biventricular conversion from all outcomes other than vital status.  Those patients with a contraindication to MRI (i.e., claustrophobia; metal screen failure; inability to lie still) will not be enrolled for participation in this study.

Potential participants will be excluded for any of the following reasons: (1) disorders that would prevent successful completion of the planned study testing (e.g., pacemaker, metal implants; claustrophobia; inability to lie still); (2) other forms of congenital heart disease requiring surgical correction; (3) inability of parent to provide consent or participate in the informed consent process.