Single-drug immunosuppression is associated with noninferior medium-term survival in pediatric heart transplant recipients.

BACKGROUND: Patients are usually maintained on at least 2 immunosuppressive drugs (ISDs) after the first year post heart transplant. Anecdotally, some children are switched to single-drug monotherapy (a single ISD) for various reasons and varying durations. Outcomes associated with differences in immunosuppression after heart transplantation are unknown for children. OBJECTIVES: A priori we defined a noninferiority hypothesis for monotherapy compared to ≥2 ISDs. The primary outcome was graft failure, a composite of death and retransplantation. Secondary outcomes included rejection, infection, malignancy, cardiac allograft vasculopathy and dialysis. METHODS: This international, multicenter, retrospective, observational cohort study used data from the Pediatric Heart Transplant Society. We included patients who underwent first-time heart transplant <18 years of age between 1999 and 2020 with ≥1 year of follow-up data available. RESULTS: Our analysis included 3493 patients with a median time post-transplant of 6.7 years. There were 893 patients (25.6%) switched to monotherapy at least once with the remaining 2600 patients always on ≥2 ISDs. The median time on monotherapy after the first year post-transplant was 2.8 years (range 1.1-5.9 years). We found an adjusted hazard ratio (HR) of 0.65 (95%CI: 0.47-0.88) favoring monotherapy compared to ≥2 ISDs (p = 0.002). There were no meaningful differences in the incidence of secondary outcomes between groups, except for a lower rate of cardiac allograft vasculopathy in patients on monotherapy (HR 0.58, 95%CI: 0.45-0.74). CONCLUSIONS: For pediatric heart transplant recipients placed on monotherapy, immunosuppression with a single ISD after the first year post-transplant was noninferior to standard therapy with ≥2 ISDs in the medium term. CONDENSED ABSTRACT: Some children are switched to a single immunosuppressive drug (ISD) for various reasons after heart transplant, but outcomes associated with differences in immunosuppression are unknown for children. We assessed graft failure in children on a single ISD (monotherapy) compared to ≥2 ISDs in a cohort of 3493 children with a first heart transplant. We found an adjusted hazard ratio of 0.65 (95%CI: 0.47-0.88) favoring monotherapy. We concluded that for pediatric heart transplant recipients placed on monotherapy, immunosuppression with a single ISD after the first year post-transplant was non-inferior to standard therapy with ≥2 ISDs in the medium term.

Association Between Venous Homografts and Allosensitization After Norwood Procedure.

BACKGROUND: Right ventricle (RV) to pulmonary artery (PA) shunts have become the shunt of choice at many centers for use during the Norwood procedure for single ventricle palliation. Some centers have begun to use cryopreserved femoral or saphenous venous homografts as an alternative to polytetrafluoroethylene (PTFE) for shunt construction. The immunogenicity of these homografts is unknown, and potential allosensitization could have significant implications on transplant candidacy. METHODS: All patients undergoing Glenn procedure at our center between 2013 and 2020 were screened. Patients who initially underwent Norwood procedure with either PTFE or venous homograft RV-PA shunt and had available pre-Glenn serum were included in the study. The primary outcome of interest was panel reactive antibody (PRA) level at the time of Glenn surgery. RESULTS: Thirty-six patients met inclusion criteria (N = 28 PTFE, N = 8 homograft). Patients in the homograft group had significantly higher median PRA levels at the time of Glenn surgery (0% [IQR 0-18] PTFE vs 94% [IQR 74-100] homograft, P = .003). There were no other differences between the two groups. CONCLUSIONS: Despite potential improvements in PA architecture, the use of venous homografts for RV-PA shunt construction at the time of Norwood procedure is associated with significantly elevated PRA level at the time of Glenn surgery. Centers should carefully consider the use of currently available venous homografts given the high percentage of these patients who may require future transplantation.

The Fontan immunophenotype and post-transplant outcomes in children: A multi-institutional study.

BACKGROUND: Patients after Fontan palliation represent a growing pediatric population requiring heart transplant (HTx) and often have lymphopenia (L) and/or hypogammaglobinemia that may be exacerbated by protein-losing enteropathy (PLE, P). The post-HTx effects of this altered immune phenotype are not well studied. METHODS: In this study of the Pediatric Heart Transplant Society Registry, 106 Fontan patients who underwent HTx between 2005 and 2018 were analyzed. The impact of lymphopenia and PLE on graft survival, infection, rejection, and malignancy was analyzed at 1 and 5 years post-HTx. RESULTS: The following combinations of lymphopenia and PLE were noted: +L+P, n = 37; +L-P, n = 23; -L+P, n = 10; and -L-P, n = 36. Graft survival between the groups was similar within the first year after transplant (+L+P: 86%, +L-P: 86%, -L+P: 87%, -L-P: 89%, p = .9). Freedom from first infection post-HTx was greatest among -L-P patients compared to patients with either PLE, lymphopenia, or both; with a 22.1% infection incidence in the -L-P group and 41.4% in all others. These patients had a significantly lower infection rate in the first year after HTx (+L+P: 1.03, +L-P: 1, -L+P: 1.3, -L-P: 0.3 infections/year, p < .001) and were similar to a non-single ventricle CHD control group (0.4 infections/year). Neither freedom from rejection nor freedom from malignancy 1 and 5 years post-HTx, differed among the groups. CONCLUSIONS: Fontan patients with altered immunophenotype, with lymphopenia and/or PLE, are at increased risk of infection post-HTx, although have similar early survival and freedom from rejection and malignancy. These data may encourage alternative immunosuppression strategies and enhanced monitoring for this growing subset of patients.

Fontan-associated liver disease after heart transplant.

BACKGROUND: Fontan associated liver disease (FALD) potentially impacts Fontan patients undergoing heart transplant. This multi-center study sought to identify pre-transplant risk factors and characterize any post-transplant liver recovery in those patients undergoing heart-alone transplant. METHODS: Review of Fontan patients at 12 pediatric institutions who underwent heart transplant between 2001-2019. Radiologists reviewed pre and post-transplant liver imaging for fibrosis. Laboratory, pathology and endoscopy studies were reviewed. RESULTS: 156 patients underwent transplant due to decreased ventricular function (49%), protein losing enteropathy (31%) or plastic bronchitis (10%); median age at transplant was 13.6 years (interquartile range IQR 7.8, 17.2) with a median of 9.3 years (IQR 3.2, 13.4) between the Fontan operation and transplant. Few patients had pre-transplant endoscopy (18%), and liver biopsy (19%). There were 31 deaths (20%). The median time from transplant to death was 0.5 years (95% Confidence Interval CI 0.0, 3.6). The five-year survival was 73% (95% CI 64%, 83%). Deaths were related to cardiac causes in 68% (21/31) and infection in 6 (19%). A pre-transplant elevation in bilirubin was a predictor of death. Higher platelet levels were protective. Immediate post-transplant elevations in creatinine, AST, ALT, and INR were predictive of death. Advanced liver fibrosis identified on ultrasound, computed tomography, or magnetic resonance imaging was not predictive of death. Liver imaging suggested some improvement in liver congestion post-transplant. CONCLUSIONS: Elevated bilirubin, but not fibrosis on liver imaging, was associated with post-heart transplant mortality in Fontan patients in this multicenter retrospective study. Additionally, heart transplant may alter the progression of FALD.

The Genetically Engineered Heart as a Bridge to Allotransplantation in Infants Just Around the Corner?

BACKGROUND: Mortality for infants on the heart transplant waitlist remains unacceptably high, and available mechanical circulatory support is suboptimal. Our goal is to demonstrate the feasibility of utilizing genetically engineered pig (GEP) heart as a bridge to allotransplantation by transplantation of a GEP heart in a baboon. METHODS: Four baboons underwent orthotopic cardiac transplantation from GEP donors. All donor pigs had galactosyl-1,3-galactose knocked out. Two donor pigs had human complement regulatory CD55 transgene and the other 2 had human complement regulatory CD46 and thrombomodulin. Induction immunosuppression included thymoglobulin, and anti-CD20. Maintenance immunosuppression was rapamycin, anti-CD-40, and methylprednisolone. One donor heart was preserved with University of Wisconsin solution and the other three with del Nido solution. RESULTS: All baboons weaned from cardiopulmonary bypass. B217 received a donor heart preserved with University of Wisconsin solution. Ventricular arrhythmias and depressed cardiac function resulted in early death. All recipients of del Nido preserved hearts easily weaned from cardiopulmonary bypass with minimal inotropic support. B15416 and B1917 survived for 90 days and 241 days, respectively. Histopathology in B15416 revealed no significant myocardial rejection but cellular infiltrate around Purkinje fibers. Histopathology in B1917 was consistent with severe rejection. B37367 had uneventful transplant but developed significant respiratory distress with cardiac arrest. CONCLUSIONS: Survival of B15416 and B1917 demonstrates the feasibility of pursuing additional research to document the ability to bridge an infant to cardiac allotransplant with a GEP heart.

Impact of induction strategy change on first-year rejection in pediatric heart transplantation at a single center-From postoperative basiliximab to either postoperative anti-thymocyte globulin or preoperative basiliximab.

BACKGROUND: Our pediatric heart transplant center transitioned from post-bypass basiliximab (BAS) induction to either anti-thymocyte globulin (ATG) or pre-bypass BAS. The purpose of this study was to compare first-year rejection rates before and after this change. METHODS: A single-center retrospective analysis was conducted of pediatric heart transplant recipients from 2010 to 2019. Primary outcome was first-year rejection. Bivariate analysis, Kaplan-Meier curves, and multivariable regression were performed across eras. RESULTS: Forty-three early era patients (55%) received post-bypass BAS, and 35 late era patients (45%) received pre-bypass BAS (n = 17) or ATG (n = 18). First-year rejection decreased in the late era (31% vs 53%, p = .05). This finding was more pronounced after excluding infants (38% vs 73%, p = .006). Late era was associated with a decreased likelihood of rejection (all cohort OR 0.19, 95% CI 0.05-0.66; infants excluded OR 0.17, 95% CI 0.04-0.61). No differences in post-transplant lymphoproliferative disease, donor-specific antibody, or infection were observed. CONCLUSIONS: Fewer late era patients receiving ATG or pre-bypass BAS induction had first-year rejection compared to the early era patients receiving standard post-bypass BAS induction. This programmatic shift in induction strategy was readily achievable and potentially effective in reducing first-year rejection.

Clinical outcomes of children receiving ABO-incompatible versus ABO-compatible heart transplantation: a multicentre cohort study.

BACKGROUND: ABO-incompatible heart transplantation increases donor availability in young children and is evolving into standard of care in children younger than 2 years. Previous smaller studies suggest similar outcomes to ABO-compatible heart transplantation, but persisting alterations of the immune system in ABO-incompatible recipients might increase the risk of some infections or benefit the graft owing to reduced HLA reactivity. We aimed to assess long-term outcomes in young children after they received ABO-incompatible or ABO-compatible heart transplantation. METHODS: In this multicentre, prospective cohort study, we analysed data from the Pediatric Heart Transplant Society registry to compare children who received ABO-incompatible or ABO-compatible heart transplantation before age 2 years between Jan 1, 1999, and June 30, 2018. Given significantly different clinical demographics between the two groups, we also matched each ABO-incompatible recipient to two ABO-compatible recipients using propensity score matching. We assessed patient and graft survival, coronary allograft vasculopathy, malignancy, acute rejection (any episode resulting in augmentation of immunosuppression), and infections (requiring intravenous antibiotic or antiviral therapy or life-threatening infections treated with oral therapy). FINDINGS: We included 2206 children who received a heart transplant before age 2 years, with 11 332·6 patient-years of cumulative observation time. Children who received an ABO-incompatible transplant (n=364) were younger and a larger proportion had congenital heart disease and ventilator and mechanical circulatory support than the ABO-compatible recipients (n=1842). After matching, only differences in blood group (more O in ABO-incompatible and more AB in ABO-compatible groups) and use of polyclonal induction therapy with anti-thymocyte globulins persisted. The two matched groups had similar post-transplantation graft survival (p=0·74), freedom from coronary allograft vasculopathy (p=0·75), and malignancy (p=0·51). ABO-incompatible recipients showed longer freedom from rejection (p=0·0021) in the overall cohort, but not after matching (p=0·48). Severe infections (p=0·0007), bacterial infections (p=0·0005), and infections with polysaccharide encapsulated bacteria (p=0·0005) that share immunological properties with blood group antigens occurred less frequently after ABO-incompatible heart transplantation. INTERPRETATION: ABO-incompatible heart transplantation for children younger than 2 years is a clinically safe approach, with similar survival and incidences of rejection, coronary allograft vasculopathy, and malignancy to ABO-compatible recipients, despite higher-risk pre-transplant profiles. ABO-incompatible transplantation was associated with less bacterial infection, particularly encapsulated bacteria, suggesting that the acquired immunological changes accompanying ABO tolerance might benefit rather than jeopardise transplanted children. FUNDING: Pediatric Heart Transplant Society.

Late Heart Transplantation in Hypoplastic Left Heart Syndrome With Intact Atrial Septum.

This case report describes 2 patients born with hypoplastic left heart syndrome and an intact atrial septum who underwent a strategy of immediate extracorporeal membrane oxygenation and left atrial decompression followed by hybrid Norwood palliation as a bridge to further palliation. Heart transplantation was ultimately performed in these 2 patients with persisting pulmonary vascular resistance abnormalities.

Attitudes to Cardiac Xenotransplantation by Pediatric Heart Surgeons and Physicians.

BACKGROUND: Cardiac transplantation in early childhood is limited by scarcity of organ donors. Advances in cardiac xenotransplantation (XTx) research suggest that xenografts may one day represent an alternative to allografts. We sought to determine the attitudes among surgeons and cardiologists in the field of pediatric cardiac transplantation toward the potential use of XTx if this clinical option were to become a reality. METHODS: A Likert-scale anonymous survey addressing the use of XTx in pediatric patients was sent to members of the Congenital Heart Surgeons (CHS) Society and the Pediatric Heart Transplant Society. Results were described and compared between the two surgeon/physician groups. RESULTS: Ninety-two CHS and 42 pediatric transplant cardiologists (PTC) responded (N = 134). The potential acceptance of XTx was high in both groups, assuming risks and results were similar to those of cardiac allotransplantation (88% CHS vs 81% PTC; P = .07). When asked if they would recommend a xenograft, if the results were anticipated to be inferior to those of cardiac allotransplantation, as a bridge to a human heart, potential acceptance fell dramatically but remained higher among CHS than PTC (41% vs 17%, p 0.02). Approximately only one-third of CHS and half of PTC preferred primary cardiac XTx for hypoplastic left heart syndrome if there was no waitlist time and had similar outcomes to allotransplantation. CONCLUSIONS: Our findings suggest that potential acceptance of XTx by CHS and PTC would not be a major barrier if XTx demonstrated similar outcomes to allotransplantation. Acceptance by other congenital heart stakeholders remains to be investigated.

Anti-Pig Antibody in Infants: Can a Genetically Engineered Pig Heart Bridge to Allotransplantation?

BACKGROUND: Patients with congenital heart disease have high heart transplant waitlist mortality, and mechanical support is suboptimal. To evaluate feasibility of cardiac grafts from a genetically engineered triple-knockout pig as a bridge to allotransplantation, preformed anti-pig antibodies were measured in pediatric and adult patients. METHODS: Flow cytometry measured serum immunoglobulin M (IgM) or IgG binding to wild-type and triple-knockout red blood cells (RBCs), with binding to human O-negative RBCs as a negative control. Group 1 comprise 84 pediatric patients and 64 healthy adults' sera with no previous cardiac surgery. Group 2 comprised 25 infant's sera postcardiac surgery, including 10 after palliation for hypoplastic left heart syndrome. RESULTS: In group 1, IgM binding to wild-type RBCs occurred in 80% of sera and IgG binding occurred in in 91% of sera. Only 3% of sera showed IgM binding to triple-knockout RBCs, and 1 (<1%) was weakly positive for IgG binding. In group 2, all 25 infants demonstrated increased IgM and IgG binding to wild-type RBCs. One patient showed minimal IgM and another showed low IgG binding to triple-knockout RBCs. No infant after stage 1 Norwood demonstrated any IgG or IgM binding. CONCLUSIONS: Preformed anti-pig antibodies may not be a barrier to heart xenotransplantation in infants, even after cardiac surgery. With adequate immunosuppressive therapy, a triple-knockout pig heart transplant might function successfully as a bridge to allotransplantation.

Impact of contrast exposure from computed tomography angiography on acute kidney injury after neonatal cardiopulmonary bypass surgery.

OBJECTIVE: Acute kidney injury (AKI) is a frequent complication after cardiopulmonary bypass (CBP) for cardiac surgery in neonates. It is unclear if exposure to computed tomography angiography (CTA) in the preoperative period increases the risk of AKI. We hypothesized a short interval between CTA and CPB surgery would be associated with higher rates of AKI in infants. DESIGN: In this single center retrospective review of patients between 2012 and 2015, neonates less than one month old were analyzed if they had CTA prior to cardiac surgery with CPB. Baseline, demographic, fluid balance, and laboratory data was analyzed. AKI was staged according to KDIGO criteria. RESULTS: Fifty-six neonates were analyzed. AKI developed in 42 (75%) of patients; severe AKI (KDIGO stages 2 and 3) occurred in 18 (32%). Patient characteristics were similar at baseline and at time of CTA between those with and without severe AKI. Patients with severe AKI had longer CPB time, lower postoperative urine output, higher peak serum creatinine, and longer hospital length of stay. When considering intervals between CTA and CPB surgery ≤1 day (n = 19), ≤3 days (n = 28), and >3 days (n = 28); there was no difference in AKI incidence nor postoperative outcomes among these three interval cohorts. CONCLUSION: Routine exposure to CTA and CPB surgery in close succession does not appear to increase the risk of AKI after neonatal cardiac surgery. Though other risks need to be weighed (eg, sedation, intubation, radiation exposure), this result may enable more liberal utilization of CTA for preoperative surgical planning of congenital heart operations in patients with unclear or complex anatomy.

Current Expectations for Cardiac Transplantation in Patients With Congenital Heart Disease.

Congenital heart disease accounts for 40% of pediatric heart transplants and presents unique challenges to the transplant team. Suitability for transplantation is defined in part by degree of sensitization, pulmonary vascular resistance, and hepatic reserves. The incremental transplant risk for patients with congenital heart disease occurs within the first 3 months, after which survival is equivalent to transplantation for cardiomyopathy. Single ventricle with prior palliation, and especially the failing Fontan, carry the highest risk for transplantation and are least amenable to bridging with mechanical circulatory support. More effective bridging to transplant with mechanical circulatory support will require improvements in the adverse event profile of available pumps and the introduction of miniaturized continuous flow technology. The major barriers to routine long-term survival are chronic allograft failure and allograft vasculopathy. Despite these many challenges, continuing improvements in the care of pediatric heart transplant patients have pushed the median posttransplant survival past 15 years for children and to 20 years for infants.

Aortic dilation in pediatric patients.

Aortic dilation at the level of the aortic root can be caused by a variety of congenital or acquired conditions that lead to weakening of the aortic wall. In this retrospective study, we sought to determine the frequency of different associated diagnoses from children with aortic dilation seen at a single institution. A total of 377 children (68 % male) met study inclusion criteria. Patients were classified based on the suspected or confirmed associated diagnosis in one of the following categories: congenital heart disease (241/377, 64 %), chromosomal (34/377, 9 %), Marfan syndrome (26/377, 7 %), other genetic and non-genetic (22/377, 6 %), Loeys-Dietz syndrome (6/377, 2 %), and unknown (48/377, 13 %). Bicuspid aortic valve was by far the most prevalent congenital heart defect (206/241, 85 %), while Turner syndrome was the most frequent chromosomal abnormality (12/34, 35 %). Patients with Marfan syndrome were more likely to have severe dilation of the ascending aorta (p = 0.002) and to require aortic root replacement surgery (p < 0.001) compared to those in other diagnosis categories. CONCLUSION: The differential diagnosis of aortic dilation is broad and requires a careful assessment of cardiac anatomy. Evaluation by a clinical geneticist in this setting should be strongly considered given the high frequency of associated genetic conditions. WHAT IS KNOWN: • Aortic dilation is frequent in bicuspid aortic valve and other congenital heart defects. • Aortic dilation can be seen in several connective tissue disorders. Limited information is available in regard to the differential diagnosis of aortic dilation in children. WHAT IS NEW: • In patients with aortic dilation concurrent congenital heart disease is frequently diagnosed. • Almost 18 % of cases in the present study had a defined presumptive or confirmed genetic diagnosis. We suggest considering a genetics evaluation in the setting of aortic dilation.

Repair of early posttransplant endomyocardial biopsy-related tricuspid regurgitation in a child.

We describe surgical repair of symptomatic tricuspid valve regurgitation in the early posttransplant period in a small child. The tricuspid valve regurgitation was due to injury to the valve and chordal apparatus during surveillance endomyocardial biopsy. The described surgical technique produced durable improvement in valve function.

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.

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.

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.