Early developmental outcome in children with hypoplastic left heart syndrome and related anomalies: the single ventricle reconstruction trial.

BACKGROUND: Survivors of the Norwood procedure may experience neurodevelopmental impairment. Clinical trials to improve outcomes have focused primarily on methods of vital organ support during cardiopulmonary bypass. METHODS AND RESULTS: In the Single Ventricle Reconstruction trial of the Norwood procedure with modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery shunt, 14-month neurodevelopmental outcome was assessed by use of the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. We used multivariable regression to identify risk factors for adverse outcome. Among 373 transplant-free survivors, 321 (86%) returned at age 14.3 ± 1.1 (mean ± SD) months. Mean PDI (74 ± 19) and MDI (89 ± 18) scores were lower than normative means (each P<0.001). Neither PDI nor MDI score was associated with type of Norwood shunt. Independent predictors of lower PDI score (R(2)=26%) were clinical center (P=0.003), birth weight <2.5 kg (P=0.023), longer Norwood hospitalization (P<0.001), and more complications between Norwood procedure discharge and age 12 months (P<0.001). Independent risk factors for lower MDI score (R(2)=34%) included center (P<0.001), birth weight <2.5 kg (P=0.04), genetic syndrome/anomalies (P=0.04), lower maternal education (P=0.04), longer mechanical ventilation after the Norwood procedure (P<0.001), and more complications after Norwood discharge to age 12 months (P<0.001). We found no significant relationship of PDI or MDI score to perfusion type, other aspects of vital organ support (eg, hematocrit, pH strategy), or cardiac anatomy. CONCLUSIONS: Neurodevelopmental impairment in Norwood survivors is more highly associated with innate patient factors and overall morbidity in the first year than with intraoperative management strategies. Improved outcomes are likely to require interventions that occur outside the operating room. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00115934.

Comparison of shunt types in the Norwood procedure for single-ventricle lesions.

BACKGROUND: The Norwood procedure with a modified Blalock-Taussig (MBT) shunt, the first palliative stage for single-ventricle lesions with systemic outflow obstruction, is associated with high mortality. The right ventricle-pulmonary artery (RVPA) shunt may improve coronary flow but requires a ventriculotomy. We compared the two shunts in infants with hypoplastic heart syndrome or related anomalies. METHODS: Infants undergoing the Norwood procedure were randomly assigned to the MBT shunt (275 infants) or the RVPA shunt (274 infants) at 15 North American centers. The primary outcome was death or cardiac transplantation 12 months after randomization. Secondary outcomes included unintended cardiovascular interventions and right ventricular size and function at 14 months and transplantation-free survival until the last subject reached 14 months of age. RESULTS: Transplantation-free survival 12 months after randomization was higher with the RVPA shunt than with the MBT shunt (74% vs. 64%, P=0.01). However, the RVPA shunt group had more unintended interventions (P=0.003) and complications (P=0.002). Right ventricular size and function at the age of 14 months and the rate of nonfatal serious adverse events at the age of 12 months were similar in the two groups. Data collected over a mean (+/-SD) follow-up period of 32+/-11 months showed a nonsignificant difference in transplantation-free survival between the two groups (P=0.06). On nonproportional-hazards analysis, the size of the treatment effect differed before and after 12 months (P=0.02). CONCLUSIONS: In children undergoing the Norwood procedure, transplantation-free survival at 12 months was better with the RVPA shunt than with the MBT shunt. After 12 months, available data showed no significant difference in transplantation-free survival between the two groups. (ClinicalTrials.gov number, NCT00115934.)

A predictive model for neurodevelopmental outcome after the Norwood procedure.

Neurodevelopmental outcomes after the Norwood procedure for single right ventricular lesions are worse than those in the normal population. It would be valuable to identify which patients at the time of Norwood discharge are at greatest risk for neurodevelopmental impairment later in childhood. As such, this study sought to construct and validate a model to predict poor neurodevelopmental outcome using variables readily available to the clinician. Using data from the 14 month neurodevelopmental outcome of the Single-Ventricle Reconstruction (SVR) trial, a classification and regression tree (CART) analysis model was developed to predict severe neurodevelopmental impairment, defined as a Psychomotor Development Index (PDI) score lower than 70 on the Bayley Scales of Infant Development-II. The model then was validated using data from subjects enrolled in the Infant Single Ventricle (ISV) trial. The PDI scores were lower than 70 for 138 (44 %) of 313 subjects. Predictors of a PDI lower than 70 were post-Norwood intensive care unit (ICU) stay longer than 46 days, genetic syndrome or other anomalies, birth weight less than 2.7 kg, additional cardiac surgical procedures, and use of five or more medications at hospital discharge. Using these risk factors, the CART model correctly identified 75 % of SVR subjects with a PDI lower than 70. When the CART model was applied to 70 subjects from the ISV trial, the correct classification rate was 67 %. This model of variables from the Norwood hospitalization can help to identify infants at risk for neurodevelopmental impairment. However, given the overall high prevalence of neurodevelopmental impairment and the fact that nearly one third of severely affected children would not have been identified by these risk factors, close surveillance and assessment for early intervention services are warranted for all infants after the Norwood procedure.

Risk factors for hospital morbidity and mortality after the Norwood procedure: A report from the Pediatric Heart Network Single Ventricle Reconstruction trial.

OBJECTIVES: We sought to identify risk factors for mortality and morbidity during the Norwood hospitalization in newborn infants with hypoplastic left heart syndrome and other single right ventricle anomalies enrolled in the Single Ventricle Reconstruction trial. METHODS: Potential predictors for outcome included patient- and procedure-related variables and center volume and surgeon volume. Outcome variables occurring during the Norwood procedure and before hospital discharge or stage II procedure included mortality, end-organ complications, length of ventilation, and hospital length of stay. Univariate and multivariable Cox regression analyses were performed with bootstrapping to estimate reliability for mortality. RESULTS: Analysis included 549 subjects prospectively enrolled from 15 centers; 30-day and hospital mortality were 11.5% (63/549) and 16.0% (88/549), respectively. Independent risk factors for both 30-day and hospital mortality included lower birth weight, genetic abnormality, extracorporeal membrane oxygenation (ECMO) and open sternum on the day of the Norwood procedure. In addition, longer duration of deep hypothermic circulatory arrest was a risk factor for 30-day mortality. Shunt type at the end of the Norwood procedure was not a significant risk factor for 30-day or hospital mortality. Independent risk factors for postoperative renal failure (n = 46), sepsis (n = 93), increased length of ventilation, and hospital length of stay among survivors included genetic abnormality, lower center/surgeon volume, open sternum, and post-Norwood operations. CONCLUSIONS: Innate patient factors, ECMO, open sternum, and lower center/surgeon volume are important risk factors for postoperative mortality and/or morbidity during the Norwood hospitalization.