Nancy S. Ghanayem

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.)

Hypoplastic Left Heart Syndrome : Current Considerations and Expectations

In the recent era, no congenital heart defect has undergone a more dramatic change in diagnostic approach, management, and outcomes than hypoplastic left heart syndrome (HLHS). During this time, survival to the age of 5 years (including Fontan) has ranged from 50% to 69%, but current expectations are that 70% of newborns born today with HLHS may reach adulthood. Although the 3-stage treatment approach to HLHS is now well founded, there is significant variation among centers. In this white paper, we present the current state of the art in our understanding and treatment of HLHS during the stages of care: 1) pre-Stage I: fetal and neonatal assessment and management; 2) Stage I: perioperative care, interstage monitoring, and management strategies; 3) Stage II: surgeries; 4) Stage III: Fontan surgery; and 5) long-term follow-up. Issues surrounding the genetics of HLHS, developmental outcomes, and quality of life are addressed in addition to the many other considerations for caring for this group of complex patients.

Home surveillance program prevents interstage mortality after the Norwood procedure

OBJECTIVE To determine whether early identification of physiologic variances associated with interstage death would reduce mortality, we developed a home surveillance program. METHODS Patients discharged before initiation of home surveillance (group A, n = 63) were compared with patients discharged with an infant scale and pulse oximeter (group B, n = 24). Parents maintained a daily log of weight and arterial oxygen saturation according to pulse oximetry and were instructed to contact their physician in case of an arterial oxygen saturation less than 70% according to pulse oximetry, an acute weight loss of more than 30 g in 24 hours, or failure to gain at least 20 g during a 3-day period. RESULTS Interstage mortality among infants surviving to discharge was 15.8% (n = 9/57) in group A and 0% (n = 0/24) in group B (P =.039). Surveillance criteria were breached for 13 of 24 group B patients: 12 patients with decreased arterial oxygen saturation according to pulse oximetry with or without poor weight gain and 1 patient with poor weight gain alone. These 13 patients underwent bidirectional superior cavopulmonary connection (stage 2 palliation) at an earlier age, 3.7 +/- 1.1 months of age versus 5.2 +/- 2.0 months for patients with an uncomplicated interstage course (P =.028). A growth curve was generated and showed reduced growth velocity between 4 and 5 months of age, with a plateau in growth beyond 5 months of age. CONCLUSION Daily home surveillance of arterial oxygen saturation according to pulse oximetry and weight selected patients at increased risk of interstage death, permitting timely intervention, primarily with early stage 2 palliation, and was associated with improved interstage survival. Diminished growth identified 4 to 5 months after the Norwood procedure brings into question the value of delaying stage 2 palliation beyond 5 months of age.

Bridging children of all sizes to cardiac transplantation: The initial multicenter North American experience with the Berlin Heart EXCOR ventricular assist device

BACKGROUND Beginning in 2000 and accelerating in 2004, the Berlin Heart EXCOR (Berlin Heart Inc Woodlands, TX) became the first pediatric-specific ventricular assist device (VAD) applied throughout North America for children of all sizes. This retrospective study analyzed the initial Berlin Heart EXCOR pediatric experience as a bridge to transplantation. METHODS Between June 2000 and May 2007, 97 EXCOR VADs were implanted in North America at 29 different institutions. The analysis is limited to 73 patients (75%) from 17 institutions, for which retrospective data were available. RESULTS Median age and weight at VAD implant were 2.1 years (range, 12 days-17.8 years) and 11 kg (range, 3-87.6 kg), respectively. The primary diagnoses were dilated cardiomyopathy in 42 (58%), congenital heart disease in 19 (26%), myocarditis in 7 (10%), and other cardiomyopathies in 5 (7%). Pre-implant clinical condition was critical cardiogenic shock in 38 (52%), progressive decline in 33 (45%), or other in 2 (3%). Extracorporeal membrane oxygenation was used as a bridge to EXCOR in 22 patients (30%). Device selection was left VAD (LVAD) in 42 (57%) and biventricular assist devices (BiVAD) in 31 (43%). The EXCOR bridged 51 patients (70%) to transplant and 5 (7%) to recovery. Mortality on the EXCOR was 23% (n = 17) overall, including 35% (11 of 31) in BiVAD vs 14% (6 of 42) in LVAD patients (p = 0.003). Multivariate analysis showed younger age and BiVAD support were significant risk factors for death while on the EXCOR. CONCLUSIONS This limited but large preliminary North American experience with the Berlin Heart EXCOR VAD as a bridge to cardiac transplantation for children of all ages and sizes points to the feasibility of this approach. The prospective investigational device evaluation trial presently underway will further characterize the safety and efficacy of the EXCOR as a bridge to pediatric cardiac transplantation.

Phenoxybenzamine improves systemic oxygen delivery after the Norwood procedure

BACKGROUND Achieving adequate systemic oxygen delivery after the Norwood procedure frequently is complicated by excessive pulmonary blood flow at the expense of systemic blood. We hypothesized that phenoxybenzamine could achieve a balanced circulation through reduction of systemic vascular resistance. METHODS In this prospective, nonrandomized study, oximetric catheters were placed in the superior vena cava for continuous monitoring of systemic venous oxygen saturation. Postoperative hemodynamic variables were compared between 7 control patients and 8 patients who received phenoxybenzamine. RESULTS The hospital survival rate was 93% (14 of 15 patients). Improvements in postoperative hemodynamics in the phenoxybenzamine group included a higher systemic venous oxygen saturation, a narrower arteriovenous oxygen content difference, a lower ratio of pulmonary to systemic flow, and a lower indexed systemic vascular resistance. In the phenoxybenzamine group, mean arterial blood pressure was related directly to systemic oxygen delivery, in contrast to the control group, where mean arterial pressure was related directly to indexed systemic vascular resistance and the ratio of pulmonary to systemic circulation. CONCLUSIONS Continuous postoperative monitoring of systemic venous oxygen saturation in a patient who has undergone the Norwood procedure provides early identification of low systemic oxygen delivery and an elevated ratio of pulmonary to systemic circulation. In this pilot study, phenoxybenzamine appeared to improve systemic oxygen delivery during the early postoperative period after the Norwood procedure. Further studies are indicated to confirm these results.

Enalapril in Infants With Single Ventricle Results of a Multicenter Randomized Trial

Background— Angiotensin-converting enzyme inhibitor therapy improves clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology have poor growth and are at risk for abnormalities in ventricular systolic and diastolic function. The ability of angiotensin-converting enzyme inhibitor therapy to preserve ventricular function and improve somatic growth and outcomes in these infants is unknown. Methods and Results— The Pediatric Heart Network conducted a double-blind trial involving 230 infants with single-ventricle physiology randomized to receive enalapril (target dose 0.4 mg · kg−1 · d−1) or placebo who were followed up until 14 months of age. The primary end point was weight-for-age z score at 14 months. The primary analysis was intention to treat. A total of 185 infants completed the study. There were 24 and 21 withdrawals or deaths in the enalapril and placebo groups, respectively (P=0.74). Weight-for-age z score was not different between the enalapril and placebo groups (mean±SE −0.62±0.13 versus −0.42±0.13, P=0.28). There were no significant group differences in height-for-age z score, Ross heart failure class, brain natriuretic peptide concentration, Bayley scores of infant development, or ventricular ejection fraction. The incidence of death or transplantation was 13% and did not differ between groups. Serious adverse events occurred in 88 patients in the enalapril group and 87 in the placebo group. Conclusions— Administration of enalapril to infants with single-ventricle physiology in the first year of life did not improve somatic growth, ventricular function, or heart failure severity. The results of this randomized trial do not support the routine use of enalapril in this population. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00113087.

Venous saturation and the anaerobic threshold in neonates after the Norwood procedure for hypoplastic left heart syndrome

BACKGROUND Reduction in oxygen delivery can lead to organ dysfunction and death by cellular hypoxia, detectable by progressive (mixed) venous oxyhemoglobin desaturation until extraction is limited at the anaerobic threshold. We sought to determine the critical level of venous oxygen saturation to maintain aerobic metabolism in neonates after the Norwood procedure (NP) for the hypoplastic left heart syndrome (HLHS). METHODS A prospective perioperative database was maintained for demographic, hemodynamic, and laboratory data. Invasive arterial and atrial pressures, arterial saturation, oximetric superior vena cava (SVC) saturation, and end-tidal CO2 were continuously recorded and logged hourly for the first 48 postoperative hours. Arterial and venous blood gases and cooximetry were obtained at clinically appropriate intervals. SVC saturation was used as an approximation of mixed venous saturation (SvO2). A standard base excess (BE) less than -4 mEq/L (BElo), or a change exceeding -2 mEq/L/h (deltaBElo), were used as indicators of anaerobic metabolism. The relationship between SvO2 and BE was tested by analysis of variance and covariance for repeated measures; the binomial risk of BElo or deltaBElo at SvO2 strata was tested by the likelihood ratio test and logistic regression, with cutoff at p < 0.05. RESULTS Complete data were available in 48 of 51 consecutive patients undergoing NP yielding 2,074 valid separate determinations. BE was strongly related to SvO2 (model R2 = 0.40, p < 0.0001) with minimal change after adjustment for physiologic covariates. The risk of anaerobic metabolism was 4.8% overall, but rose to 29% when SvO2 was 30% or below (p < 0.0001). Survival was 100% at 1 week and 94% at hospital discharge. CONCLUSIONS Analysis of acid-base changes revealed an apparent anaerobic threshold when SvO2 fell below 30%. Clinical management to maintain SvO2 above this threshold yielded low mortality.

Neurodevelopmental Outcomes After Cardiac Surgery in Infancy

BACKGROUND: Neurodevelopmental disability is the most common complication for survivors of surgery for congenital heart disease (CHD). METHODS: We analyzed individual participant data from studies of children evaluated with the Bayley Scales of Infant Development, second edition, after cardiac surgery between 1996 and 2009. The primary outcome was Psychomotor Development Index (PDI), and the secondary outcome was Mental Development Index (MDI). RESULTS: Among 1770 subjects from 22 institutions, assessed at age 14.5 ± 3.7 months, PDIs and MDIs (77.6 ± 18.8 and 88.2 ± 16.7, respectively) were lower than normative means (each P < .001). Later calendar year of birth was associated with an increased proportion of high-risk infants (complexity of CHD and prevalence of genetic/extracardiac anomalies). After adjustment for center and type of CHD, later year of birth was not significantly associated with better PDI or MDI. Risk factors for lower PDI were lower birth weight, white race, and presence of a genetic/extracardiac anomaly (all P ≤ .01). After adjustment for these factors, PDIs improved over time (0.39 points/year, 95% confidence interval 0.01 to 0.78; P = .045). Risk factors for lower MDI were lower birth weight, male gender, less maternal education, and presence of a genetic/extracardiac anomaly (all P < .001). After adjustment for these factors, MDIs improved over time (0.38 points/year, 95% confidence interval 0.05 to 0.71; P = .02). CONCLUSIONS: Early neurodevelopmental outcomes for survivors of cardiac surgery in infancy have improved modestly over time, but only after adjustment for innate patient risk factors. As more high-risk CHD infants undergo cardiac surgery and survive, a growing population will require significant societal resources.

Transplantation-Free Survival and Interventions at 3 Years in the Single Ventricle Reconstruction Trial

Background— In the Single Ventricle Reconstruction (SVR) trial, 1-year transplantation-free survival was better for the Norwood procedure with right ventricle–to–pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt (MBTS). At 3 years, we compared transplantation-free survival, echocardiographic right ventricular ejection fraction, and unplanned interventions in the treatment groups. Methods and Results— Vital status and medical history were ascertained from annual medical records, death indexes, and phone interviews. The cohort included 549 patients randomized and treated in the SVR trial. Transplantation-free survival for the RVPAS versus MBTS groups did not differ at 3 years (67% versus 61%; P=0.15) or with all available follow-up of 4.8±1.1 years (log-rank P=0.14). Pre-Fontan right ventricular ejection fraction was lower in the RVPAS group than in the MBTS group (41.7±5.1% versus 44.7±6.0%; P=0.007), and right ventricular ejection fraction deteriorated in RVPAS (P=0.004) but not MBTS (P=0.40) subjects (pre-Fontan minus 14-month mean, −3.25±8.24% versus 0.99±8.80%; P=0.009). The RVPAS versus MBTS treatment effect had nonproportional hazards (P=0.004); the hazard ratio favored the RVPAS before 5 months (hazard ratio=0.63; 95% confidence interval, 0.45–0.88) but the MBTS beyond 1 year (hazard ratio=2.22; 95% confidence interval, 1.07–4.62). By 3 years, RVPAS subjects had a higher incidence of catheter interventions (P<0.001) with an increasing HR over time (P=0.005): <5 months, 1.14 (95% confidence interval, 0.81–1.60); from 5 months to 1 year, 1.94 (95% confidence interval, 1.02–3.69); and >1 year, 2.48 (95% confidence interval, 1.28–4.80). Conclusions— By 3 years, the Norwood procedure with RVPAS compared with MBTS was no longer associated with superior transplantation-free survival. Moreover, RVPAS subjects had slightly worse right ventricular ejection fraction and underwent more catheter interventions with increasing hazard ratio over time. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00115934.

Fontan Palliation in the Modern Era: Factors Impacting Mortality and Morbidity

BACKGROUND Advances in management of the Fontan patient include interval superior cavopulmonary shunt, total cavopulmonary connection, either lateral tunnel or extracardiac conduit, and the use of a fenestration. Coincident with these improvements, Fontan palliation has been applied to a wider ranger of anatomic subgroups. METHODS A cross-sectional analysis of 256 consecutive patients undergoing a total cavopulmonary connection Fontan after superior cavopulmonary shunt between January 1, 1994, and June 30, 2007 were studied. Fenestration was used selectively. Fontan failure was defined as death, transplant, or takedown. Event-free survival was defined as freedom from death, transplant, Fontan takedown, functional class III to IV, pacemaker, antiarrhythmic medication, protein-losing enteropathy, stroke, or thrombus. RESULTS Survival was 97% +/- 1%, 96% +/- 1%, and 94% +/- 2%, respectively, at 1, 5, and 10 years. Event-free survival was 96% +/- 1%, 87% +/- 3%, and 64% +/- 6%, respectively, at 1, 5, and 10 years. Factors predicting worse event-free survival included longer cross-clamp time (p = 0.003), fenestration (p = 0.014), and longer hospital length of stay (p = 0.016). Ventricular morphology did not predict outcome. Left ventricle (n = 113, 44%) versus right ventricle (n = 142, 56%) failure-free survival (death, transplant, or Fontan takedown) at 10 years was 92% +/- 4% versus 91% +/- 3%, respectively (p = 0.19). Left ventricle versus right ventricle event-free survival at 10 years was 75% +/- 7% versus 67% +/- 9%, respectively (p > 0.1). CONCLUSIONS Survival for patients undergoing a completion Fontan in the current era is excellent, but patients remain at risk for morbid events. In the intermediate follow-up period, we could not identify a difference in outcome between dominant left and right ventricle morphology.