Waldemar F. Carlo

Interstage attrition between bidirectional Glenn and Fontan palliation in children with hypoplastic left heart syndrome.

OBJECTIVE With improving operative mortality for staged palliation of hypoplastic left heart syndrome, interstage death accounts for an increasing proportion of hypoplastic left heart syndrome mortality. We investigated risk factors for death or cardiac transplantation during the interstage period between bidirectional Glenn and Fontan procedures in children with hypoplastic left heart syndrome. METHODS Patients with hypoplastic left heart syndrome who underwent bidirectional Glenn between August 1995 and June 2007 were screened. Standard risk patients, defined by having been discharged after both Norwood and bidirectional Glenn, were included for analysis. Patient demographic, echocardiographic, cardiac catheterization, and operative data were reviewed. Interstage attrition was defined as death or cardiac transplantation more than 30 days after bidirectional Glenn and before the Fontan procedure. Statistical analysis was carried out using the Student t test, Pearson chi-square correlation, and Cox proportional hazard modeling for multivariable analysis. RESULTS Ninety-two patients with hypoplastic left heart syndrome were alive at 30 days after bidirectional Glenn. Of these patients, 8 died and 3 underwent cardiac transplantation at a median of 391 days (range, 59-1175 days) after bidirectional Glenn, yielding an interstage attrition rate of 12%. Removing the 7 patients who are still awaiting Fontan (but all of whom are at least 3.5 years after bidirectional Glenn) adjusts the attrition rate to 13%. Interstage attrition did not correlate with hemodynamic data obtained at cardiac catheterization, aortic arch obstruction, or right ventricular dysfunction. Multivariable analysis demonstrated that the presence of moderate or severe tricuspid valve regurgitation (hazard ratio, 6.02; 95% confidence interval, 1.56-23.24; P < .01) and weight z score (hazard ratio, 0.38; 95% confidence interval, 0.16-0.88; P = .02) were independent preoperative risk factors for interstage attrition. CONCLUSIONS Interstage attrition between bidirectional Glenn and Fontan procedures occurred in 12% of our study population. Moderate or greater tricuspid valve regurgitation and low weight z score at the time of bidirectional Glenn are important risk factors for interstage attrition between the bidirectional Glenn and Fontan procedures in children with hypoplastic left heart syndrome.

Root dilation in patients with truncus arteriosus.

OBJECTIVE A dilated aortic root is a common finding in children and adults with some forms of congenital heart defects. No data exist on root dilation in truncus arteriosus. We sought to delineate root dimensions across a population of patients with truncus arteriosus. DESIGN We performed a single-center retrospective review of all patients with truncus arteriosus. Demographic information, clinical history, and most recent echocardiographic data were evaluated. RESULTS We identified 76 patients whose most recent study was at a median age of 5.4 years (range 0--32.7 years). Mean truncal root z-score was 5.1 ± 2.3. All but three patients had truncal root z-scores greater than or equal to 2. Truncal root z-scores remained stable with increasing body surface area and age. There were no cases of dissection or rupture. Six patients underwent truncal root surgery, typically for indications of root dilation with significant truncal valve insufficiency and left ventricular dilation. CONCLUSIONS In conclusion, mean truncal root z-score was 5, and all but three patients had truncal root z-scores greater than or equal to 2. Although repeat surgical intervention was rare and major complications related to root dilation did not occur in our cohort, further studies with longitudinal follow-up into adulthood are needed.

Mechanical Circulatory Support: Strategies and Outcomes in Pediatric Congenital Heart Disease

Patients with acute or progressive heart failure in the setting of congenital heart disease may need mechanical circulatory support (MCS) to enhance survival while awaiting cardiac transplantation. Because the majority of MCS devices are implanted after prior cardiac operations, special precautions are necessary at the time of implant. MCS in single ventricle patients usually requires ventricular and aortic cannulation, with a systemic to pulmonary artery shunt for pulmonary blood flow. Limited outcomes data is available, with less than 15% of pediatric MCS patients having congenital heart disease. The Berlin EXCOR is the only durable device currently available for infants. Neurologic complications are the major cause of mortality, and survival during support is poor for infants <5 kg. Patients post-Fontan with acute cardiac failure and/or respiratory failure are at high risk for death before transplant and should be considered for MCS therapy. Several emerging miniature continuous flow devices will soon broaden the landscape of available pediatric devices.

Single-center experience with extracorporeal photopheresis in pediatric heart transplantation

BACKGROUND The pediatric heart transplant literature contains little information regarding extracorporeal photopheresis (ECP), despite International Society for Heart and Lung Transplantation guidelines recommending it for recurrent/recalcitrant rejection. We report our experience with ECP in pediatric heart transplantation. METHODS Data were obtained on heart transplant patients who were aged ≤ 18 years at the time of transplantation and received ECP between 1990 and 2012 at our institution. RESULTS Twenty heart transplant patients underwent 22 courses of ECP. Median ages were 12.7 years (range, 0.3-18.5 years) at transplant and 15.3 years (range, 7.3-31 years) at initial ECP. Median time from transplant to ECP was 1.4 years (range, 0.1-12.6 years). The median ECP duration was 5.8 months (range, 1.9-16.1 months). Indications for ECP included rejection with hemodynamic compromise (HC) in 4 patients, rejection without HC in 12, and prophylaxis in 2. Eleven patients died at a median time of 3.1 years after the start of ECP. Survival after ECP was 84% at 1 year and 53% at 3 years. Eleven patients were considered non-compliant and had a trend toward lower survival of 75% at 1 year and 18% at 3 years (p = 0.06 compared with compliant patients). One patient developed Pneumocystis carinii pneumonia during ECP and post-transplant lymphoproliferative disease 21 months after finishing ECP. No other adverse effects or infectious complications associated with ECP were noted. CONCLUSIONS This case series represents the largest reported experience with ECP in pediatric heart transplantation. ECP can be safely applied in this patient group. Despite EPC, non-compliant patients showed a trend toward lower survival than compliant patients.

Impact of initial Norwood shunt type on young hypoplastic left heart syndrome patients listed for heart transplant: A multi-institutional study

BACKGROUND Pulmonary blood flow during Stage 1 (Norwood) palliation for hypoplastic left heart syndrome (HLHS) is achieved via modified Blalock-Taussig shunt (MBT) or right ventricle to pulmonary artery conduit (RVPA). Controversy exists regarding the differential impact of shunt type on outcome among those who require transplantation early in life. In this study we explored waitlist and post-transplant outcomes within this sub-population stratified by shunt type. METHODS Eligible patients were enrolled through the Pediatric Heart Transplant Study (PHTS) database. Patients included those listed for heart transplantation at 1 of 35 participating centers, all of whom were <6 years of age and with a diagnosis of HLHS (and variants) status post Stage 1 palliation with MBT or RVPA. Standard risk factors for death were analyzed using multivariable hazards modeling. RESULTS Between 2010 and 2013, 190 patients were identified. Compared with the RVPA group (n = 111), the MBT group (n = 79) was less likely to have undergone a Glenn palliation (41% vs 73%, p < 0.001), were younger at listing (median age 1.3 vs 1.8 years, p = 0.05), had lower median weight (7.9 vs 9.4 kg, p = 0.02), and were more likely to be mechanically ventilated at listing (35% vs 22%, p = 0.04). There were no significant differences in median waitlist time (1.7 vs 2.6 months, p = 0.2) or rate of transplantation (61% vs 60%, p = 1.0). Among waitlisted patients, 3-month survival was less for MBT compared with RVPA patients (74% vs 91%, p = 0.02). Patients who had not yet achieved Glenn palliation before listing had lower waitlist 3-month survival (76% vs 90%, p = 0.02). In MBT infants <1 year old, there was a trend toward improved survival in those with Glenn palliation compared to those without (100% vs 68%, p = 0.08). Early post-transplant mortality rates were similar between the RVPA and MBT groups (p = 0.4) with overall survival 84% at 1 year. CONCLUSIONS Among HLHS patients, the need for transplant before Glenn palliation is associated with poorer waitlist survival. Waitlist survival is poorer in the MBT group, with this difference driven by pre-Glenn MBT infants. Post-transplant outcomes were unaffected by shunt type.

Chronic Exposure to Cigarette Smoke Extract Impairs Endothelium-Dependent Relaxation of Chicken Embryo Pulmonary Arteries

Maternal smoking may increase the risk for various adverse neonatal outcomes including persistent pulmonary hypertension of the newborn (PPHN). We investigated whether chronic prenatal cigarette smoke extract (CSE) exposure could produce abnormal vasoreactivity in pulmonary arteries. Daily injections of CSE (diluted in phosphate buffered saline) or vehicle were added to the air cells of fertilized eggs starting on day 5 of the 21-day incubation period of the chicken embryo. On day 19, pulmonary arteries were dissected out and their contractile properties were assessed using small vessel myography. Endothelium-dependent and endothelium-independent vasorelaxations were examined by using acetylcholine (ACh, 10–8 to 10–4M) and sodium nitroprusside (SNP, 10–8 to 10–4M), respectively. The drug concentration inducing 50% of the maximal relaxation was determined for each concentration-response curve and expressed as negative log molar (pD2). Exposure to CSE significantly decreased the sensitivity of pulmonary arteries to ACh (pD2 control group: 7.29 ± 0.24; pD2 CSE-exposed group 6.24 ± 0.12, p < 0.05). SNP elicited similar responses in vessels of both groups at all tested concentrations. In conclusion, chronic prenatal exposure to CSE impaired endothelium-dependent but not endothelium-independent vasodilation in chicken embryo pulmonary arteries. This observation suggests that cigarette smoke components may produce deleterious effects on fetal vascular endothelial vasorelaxant pathways, leading to the development of adverse outcomes such as PPHN.

Postoperative serum cortisol concentration and adrenal insufficiency in neonates undergoing open-heart surgery.

Background: We sought to determine whether immediate postoperative serum cortisol concentration predicts adrenal insufficiency in neonates after cardiac surgery with cardiopulmonary bypass. We hypothesized that cortisol <10 µg/dL would be associated with increased catecholamine requirements and fluid resuscitation and would predict hemodynamic responsiveness to exogenous steroids. Methods: Retrospective study of 41 neonates was carried out for the levels of cortisol in the immediate postoperative period; of whom, 15 received steroids due to high levels of inotropic support. Laboratory and clinical outcomes were collected. Results: Median cortisol was 12 µg/dL (interquartile range: 5.2-27.4). Levels of cortisol <10 µg/dL was not associated with any clinical variable indicative of increased illness severity. Peak lactate (9.1 vs 11.8 mmol/L, P = .04) and maximum arteriovenous saturation difference ([Sao 2 − Svo 2] 28% vs 32%, P = .05) were both lower among patients with levels of cortisol <10 µg/dL. Six (40%) patients had a significant hemodynamic improvement within 24 hours after receiving steroids (responders), although there was no statistical difference between levels of cortisol in responders versus nonresponders. Level of cortisol was positively correlated with maximum lactate (P < .001), maximum Sao 2 − Svo 2 (P < .001), maximum inotrope score (P = .014), initial 24-hour fluid intake (P = .012), and time to negative fluid balance (P = .008) and was negatively correlated with initial 24-hour urine output (P < .001). Conclusions: Low cortisol obtained in the immediate postoperative period is not associated with worse postoperative outcomes or predictive of steroid responsiveness. In contrast, elevated levels of cortisol are positively correlated with severity of illness. The use of an absolute cortisol threshold to identify adrenal insufficiency and/or guide steroid therapy in neonates after cardiac surgery is unjustified.

Inhaled nitric oxide improves oxygen saturation in children with pulmonary arteriovenous malformations after the Fontan procedure.

Objective: To report the utility of inhaled nitric oxide to ameliorate excessive hypoxemia in children with pulmonary arteriovenous malformations after the Fontan procedure. Design: Case series. Setting: A tertiary pediatric cardiac intensive care unit in a freestanding childrens hospital. Patients: Three children with complex congenital heart disease and pulmonary arteriovenous malformations who underwent the Fontan procedure. Interventions: The 3 patients all exhibited moderate-to-severe hypoxemia in the immediate postoperative period. The hypoxemia persisted despite mechanical ventilation and oxygen at an Fio2 of 1.0. Inhaled nitric oxide was initiated with immediate and dramatic improvements in oxygen saturation in all patients. All patients were eventually weaned off inhaled nitric oxide. Conclusions: The use of inhaled nitric oxide in patients with pulmonary arteriovenous malformations after having the Fontan procedure improves hypoxemia and may potentially reduce postoperative morbidity, unnecessary testing, and duration of hospital stay.

Systemic effects of intracoronary nitroglycerin during coronary angiography in children after heart transplantation.

Coronary spasm during coronary angiography for vasculopathy in children can be prevented by the intracoronary administration of nitroglycerin. We reviewed the anesthesia and catheterization reports and charts for pediatric transplant recipients who underwent angiography from 2005 through 2010. Correlation analysis was used to study the relation of post-injection systolic blood pressure (SBP) to nitroglycerin dose. Forty-one angiographic evaluations were performed on 25 patients (13 male and 12 female). Mean age was 9.9 ± 3.2 years (range, 3.3-16.1 yr). The mean total dose of nitroglycerin was 2.93 ± 1.60 µg/kg (range, 1-8 µg/kg). There was a significant drop between the baseline SBP (mean, 106 ± 21.6 mmHg) and the lowest mean SBP before nitroglycerin administration (78 ± 13.2, P <0.0001, paired t test). There was no significant additional change in SBP (mean after nitroglycerin administration, 80.7 ± 13.1 mmHg; P = 0.2). There was a significant drop in lowest heart rate between baseline (109 ± 16.5 beats/min) and before nitroglycerin administration (89 ± 14.3 beats/min; P <0.0001, paired t test). There was no significant additional change in heart rate (mean heart rate after nitroglycerin, 84 ± 17.7 beats/min; P = 0.09). There were 2 interventions for SBP before nitroglycerin and 2 after nitroglycerin. One child experienced a transient ST-T-segment change during angiography after nitroglycerin. In the highest dose range, the additional decrease in SBP was 7.2 mmHg (P=0.03). Routine intracoronary nitroglycerin administration in this dose range produced no significant changes in SBP or heart rate in children.

Practice trends over time in the care of infants with hypoplastic left heart syndrome: A report from the National Pediatric Cardiology Quality Improvement Collaborative.

OBJECTIVE The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) was established in 2008 to improve outcomes of hypoplastic left heart syndrome (HLHS) during the interstage period. They evaluated changes in patient variables and practice variation between early and late eras. DESIGN Data including demographic, operative, discharge, and follow-up variables from the first 100 patients (6/2008-1/2010) representing 18 centers were compared with the most recent 100 patients (1/2014-11/2014) from these same centers. RESULTS Prenatal diagnosis increased from 69% to 82% (P = .05). There were no differences in gestational age or weight at Norwood. A composite of any preoperative risk factor occurred more frequently in the early era (59% vs. 34%, P < .01). While mean age at Norwood was similar (8.3 vs. 6.6 days, P = .2), the standard deviation was significantly lower in the recent era (10.4-6.4 days, P = .04). Use of RV-PA conduit increased (67%-84%, P < .01). Rates of complete discharge communication with both the primary care physician (31%-97%, P < .01) and primary cardiologist (44%-97%, P < .01) increased substantially. There were limited changes in feeding strategies. Use of home monitoring program increased (76%-99%, P < .01) with all participants in the late era monitoring both oxygen saturation and weight. CONCLUSIONS Among NPC-QIC centers contributing patients to both eras, there were significant changes in preoperative risk factors, surgical strategy, discharge communication, and interstage care. Further study is required to determine an association between these changes and decreased mortality.