Heart Transplantation for Pediatric and Congenital Cardiac Disease: A Comparison of Two Eras over 23 Years and 188 Transplants at a Single Institution.

BACKGROUND: To assess changes in patterns of practice and outcomes over time, we reviewed all patients who underwent heart transplantation (HTx) at our institution and compared two consecutive eras with significantly different immunosuppressive protocols (cohort 1 [80 HTx, June 1995-June 2006]; cohort 2 [108 HTx, July 2006-September 2018]). METHODS: Retrospective study of 180 patients undergoing 188 HTx (June 1995-September 2018; 176 first time HTx, 10 second HTx, and 2 third HTx). In 2006, we commenced pre-HTx desensitization for highly sensitized patients and started using tacrolimus as our primary postoperative immunosuppressive agent. The primary outcome was mortality. Survival was modeled by the Kaplan-Meier method. Univariable and multivariable Cox proportional hazard models were created to identify prognostic factors for survival. RESULTS: Our 188 HTx included 18 neonates, 85 infants, 83 children, and 2 adults (>18 years). Median age was 260.0 days (range: 5 days-23.8 years). Median weight was 7.5 kg (range: 2.2-113 kg). Patients in cohort 1 were less likely to have been immunosensitized preoperatively (12.5% vs 28.7%, P = .017). Nevertheless, Kaplan-Meier analysis suggested superior survival in cohort 2 (P = .0045). Patients in cohort 2 were more likely to be alive one year, five years, and ten years after HTx. Multivariable analysis identified the earlier era (hazard ratio [HR] [95% confidence interval] for recent era = 0.32 [0.14-0.73]), transplantation after prior Norwood operation (HR = 4.44 [1.46-13.46]), and number of prior cardiac operations (HR = 1.33 [1.03-1.71]) as risk factors for mortality. CONCLUSIONS: Our analysis of 23 years of pediatric and congenital HTx reveals superior survival in the most recent 12-year era, despite the higher proportion of patients with elevated panel reactive antibody in the most recent era. This improvement was temporally associated with changes in our immunosuppressive strategy.

Outcomes of low-intensity biopsy surveillance for rejection in paediatric cardiac transplantation.

BACKGROUND: Significant inter-centre variability in the intensity of endomyocardial biopsy surveillance for rejection following paediatric cardiac transplantation has been reported. Our aim was to determine if low-intensity biopsy surveillance with two scheduled biopsies in the first year would produce outcomes similar to published registry outcomes. METHODS: A retrospective study of paediatric recipients transplanted between 2008 and 2014 using a low-intensity biopsy protocol consisting of two surveillance biopsies at 3 and 12-13 months in the first post-transplant year, then annually thereafter. Additional biopsies were performed based on echocardiographic and clinical surveillance. Excluded were recipients that were re-transplanted or multi-organ transplanted or were followed at another institution. RESULTS: A total of 81 recipients in the first 13 months after transplant underwent an average of 2 (SD ± 1.3) biopsies, 24 ± 6.8 echocardiograms, and 17 ± 4.4 clinic visits per recipient. During the 13-month period, 19 recipients had 24 treated rejection episodes, with the first at an average of 2.8 months post-transplant. The 3-, 12-, 36-, and 60-month conditional on discharge graft survival were 100%, 98.8%, 98.8%, and 90.4%, respectively, comparable to reported figures in major paediatric registries. At a mean follow-up of 4.7 ± 2.1 years, four patients (4.9%) developed cardiac allograft vasculopathy, three (3.7%) developed a malignancy, and seven (8.6%) suffered graft loss. CONCLUSION: Rejection surveillance with a low-intensity biopsy protocol demonstrated similar intermediate-term outcomes and safety measures as international registries up to 5 years post-transplant.

A tale of two cases of pulmonary arteriovenous malformation: How they fared after cardiac transplantation.

BACKGROUND: In single ventricle patients, aortopulmonary collaterals (APCs) and pulmonary arteriovenous malformations (PAVMs) following superior cavopulmonary shunt (CPS) can complicate orthotopic heart transplant (OHT) by cyanosis and hemoptysis. Although PAVMs can regress with the restoration of hepatic venous flow to the pulmonary circulation, the effects of hypoxemia on the "unconditioned" allograft are not known. CASES: Two patients with significant PAVMs after CPS were cyanotic following OHT. One patient with predominantly unilateral left PAVMs had arterial saturation levels less than 70% despite pulmonary vasodilators and ventilation. A custom flow restrictor-covered stent was deployed in the pulmonary artery of the affected side, redirecting the blood flow to the contralateral lung, immediately improving cyanosis. When the PAVMs regressed, the flow restrictor stent was dilated to eliminate the constriction. The second patient with PAVMs had cyanosis and severe hemoptysis from APCs post-OHT. The APCs required an extensive coil embolization, while the cyanosis responded to oxygen and pulmonary vasodilators. Both recipients did well with gradual resolution of PAVMs within 8 months. CONCLUSIONS: Despite cyanosis from right-to-left intrapulmonary shunting, allograft function recovered. Novel transcatheter interventions can play a role in patients with significant APCs or PAVM following cardiac transplantation.

Feasibility and interpretation of global longitudinal strain imaging in pediatric heart transplant recipients.

Evaluation of myocardial mechanics after heart transplant is important in monitoring allograft function and identifying rejection. Speckle tracking global longitudinal strain (GLS) may be more sensitive to early regional changes from rejection. This study aimed to determine feasibility of GLS in pediatric hearts during surveillance echocardiograms, compare their GLS to published norms (-18% to -22%), and assess association of GLS with other indices of graft function. Retrospective review of transplant echocardiograms from 2013 to 2014. Philips QLAB was used for post-acquisition GLS analysis. Multiple linear regression was used to assess the association of GLS with echocardiographic/catheterization indices, and B-type natriuretic peptide (BNP). Forty-seven patients (84 studies) were included. Calculation of GLS was feasible in 82 studies (97%) with inter- and intra-observer variability of 0.71 and 0.69. Patients (n=9) with rejection had GLS of -16.4% (SD=3.5%) compared to those without [-16.8% (SD=3.7%)]. GLS worsened linearly with increasing Ln(BNP) (P=<.001), left ventricular volume in diastole (P=<.001), septal a' wave (P=<.001), and pulmonary capillary wedge pressure (P=<.001). Speckle tracking-based GLS is feasible and reproducible in pediatric heart recipients and is reduced at baseline. The role of GLS and BNP in detecting early systolic dysfunction warrants further investigation.

Ex vivo paracrine properties of cardiac tissue: Effects of chronic heart failure.

BACKGROUND: Cardiac regenerative responses are responsive to paracrine factors. We hypothesize that chronic heart failure (HF) in pediatric patients affects cardiac paracrine signaling relevant to resident c-kit(+)cluster of differentiation (CD)34- cardiac stem cells (CSCs). METHODS: Discarded atrial septum (huAS) and atrial appendages (huAA) from pediatric patients with HF (huAA-HF; n = 10) or without HF (n = 3) were explanted and suspension explant cultured in media. Conditioned media were screened for 120 human factors using unedited monoclonal antibody-based arrays. Significantly expressed (relative chemiluminescence >30 of 100) factors are reported (secretome). Emigrated cells were immunoselected for c-kit and enumerated as CSCs. RESULTS: After culture Day 7, CSCs emigrate from huAA but not huAS. The huAA secretome during CSC emigration included hepatocyte growth factor (HGF), epithelial cell-derived neutrophil attractant-78 (ENA-78)/chemokine (C-X-C motif) ligand (CXCL) 5, growth-regulated oncogene-α (GRO-α)/CXCL1, and macrophage migration inhibitory factor (MIF), candidate pro-migratory factors not present in the huAS secretome. Survival/proliferation of emigrated CSCs required coculture with cardiac tissue or tissue-conditioned media. Removal of huAA (Day 14) resulted in the loss of all emigrated CSCs (Day 28) and in decreased expression of 13 factors, including HGF, ENA-78/CXCL5, urokinase-type plasminogen activator receptor (uPAR)/CD87, and neutrophil-activating protein-2 (NAP-2)/CXCL7 candidate pro-survival factors. Secretomes of atrial appendages from HF patients have lower expression of 14 factors, including HGF, ENA-78/CXCL5, GRO-α/CXCL1, MIF, NAP-2/CXCL7, uPAR/CD87, and macrophage inflammatory protein-1α compared with AA from patients without HF. CONCLUSIONS: Suspension explant culturing models paracrine and innate CSC interactions in the heart. In pediatric patients, heart failure has an enduring effect on the ex vivo cardiac-derived secretome, with lower expression of candidate pro-migratory and pro-survival factors for CSCs.

Human leukocyte antigen sensitization in pediatric patients exposed to mechanical circulatory support.

Human leukocyte antigen (HLA) sensitization of pediatric heart recipients increases their risk of rejection and graft loss. As more children are placed on mechanical circulatory support (MCS) as a bridge to transplant, the risk factors for development of sensitization warrant further study. A single-center retrospective review of 36 children who received MCS identified 22 patients supported with either extracorporeal membrane oxygenation (ECMO) (n = 15) or ECMO-ventricular assist device (VAD) (n = 7) with paired (pre-MCS/post-MCS) panel reactive antibodies (PRA) or only negative post-MCS PRAs. Four patients (18%) became sensitized post-MCS (one ECMO-only patient, three ECMO-VAD patients). No difference was found between sensitized and nonsensitized patients in terms of congenital heart disease versus primary cardiomyopathy (p = 0.096), duration of MCS (38 days vs. 14 days, p = 0.233), or volume of blood product transfusions (358.6 ml/kg vs. 612.7 ml/kg, p = not significant). By multivariable analysis, the association of sensitization with older age at MCS (p = 0.076) and history of homograft (p = 0.064) approached significance. Pediatric patients supported with MCS are at low risk of developing HLA sensitization. Diagnosis, MCS duration, and volume of transfused blood products do not appear to be associated with HLA sensitization, but there is a suggestion of an association with older age at MCS and history of a homograft.

Propranolol responsiveness in vascular tumors is not determined by qualitative differences in adrenergic receptors.

Propranolol, a beta 1 (ADBR1) and beta 2 (ADBR2) adrenergic receptor blocker, accelerates regression of proliferating infantile hemangiomas (IH-P) while not affecting non-involuting congenital hemangiomas (NICH) and nonproliferating IH (IH-NP). To determine the expression of ADBRs in vascular tumors, immunofluorescent staining and confocal microscopy were employed to determine the in situ cellular distribution of ADBRs in formalin-fixed paraffin-embedded tissue sections of IH-P, IH-NP, and NICH. In situ cellular proliferation, indexed by Ki-67 expression, distinguished IH-P (n = 3) from both IH-NP (n = 3) and NICH (n = 2). In IH-P, IH-NP, and NICH tumor sections, both ADBR1 and ADBR2 were co-localized in both endothelial cells (ECs; GLUT1(+) in IH; CD31+ in NICH) and pericytes (smooth muscle actin). We tentatively conclude that either EC and/or pericytes in IH-P could be target(s) of propranolol. Cell proliferation, but not absence of either class of ADBR, distinguished the propranolol responsive IH-P from the nonresponsive IH-NP and NICH.

Donor-specific antibodies: can they predict C4d deposition in pediatric heart recipients?

There is limited evidence regarding the utility of circulating DSA in surveillance for AMR of pediatric heart recipients. Our hypothesis is that quantitation of DSA improves their power for predicting a C4d+, an integral component in the current diagnostic criteria of AMR. All pediatric recipients transplanted between 10/2005 and 1/2011 were retrospectively reviewed for DSA determined within 48 h of EMB. C4d+ was defined as >25% endothelial cell staining by immunohistochemical methods. A total of 183 paired DSA-EMB determinations were identified in 60 patients, a median of three paired studies per patient (range: 1-9). DSA were detected in 60 of these determinations. A receiver-operating characteristic plot identified a threshold single-antibody MFI of >6000 that strongly correlated with C4d+ (p < 0.0001) with a high negative predictive value (0.97) and specificity (0.95). The sensitivity and positive predictive values were 0.71 and 0.60, respectively. The predictive power of single-antigen DSA for C4d deposition was improved in pediatric heart recipients using an institution-specific MFI threshold value. In post-transplant care, quantitative DSA should be an essential component in the surveillance for AMR.

Propranolol treatment of infantile hemangiomas: anticipatory guidance for parents and caretakers.

Infantile hemangiomas (IH) are benign tumors of endothelial-like cells. Occurring in 4.5% of children, they are the most common tumor of childhood. The great majority of patients with IH will not need treatment, but 10% require systemic treatment. Many treatments have been described for the treatment of IH, but the Food and Drug Administration has not approved any. Over the last decade, numerous reports of successful treatment of IH with propranolol have been published. Despite its widespread use, little is known regarding the proper dosing, safety monitoring, and during of treatment or long-term outcomes for propranolol treatment of IH. Given its potential side effects, detailed education regarding proper administration of the medication as well as warning signs to watch for is necessary for parents and caretakers. Herein, we provide a parental handout that practitioners can individually tailor for use in their clinics when educating parents and caretakers about the use of propranolol for IH. Updates will also need to be made as more is learned regarding the optimal dosing and safety monitoring when using propranolol for this indication.

Initiation and use of propranolol for infantile hemangioma: report of a consensus conference.

Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in nature and anticipate that they will be revised as more data are made available.

'Shovel-Ready' applications of stem cell advances for pediatric heart disease.

PURPOSE OF REVIEW: The past decade has seen remarkable advances in the field of stem cell biology. Many new technologies and applications are passing the translational phase and likely will soon be relevant for the clinical pediatric cardiologist. RECENT FINDINGS: This review will focus on two advances in basic science that are now translating into clinical trials. The first advance is the recognition, characterization, and recent therapeutic application of resident cardiac progenitor cells (CPCs). Early results of adult trials and scattered case reports in pediatric patients support expanding CPC-based trials for end-stage heart failure in pediatric patients. The relative abundance of CPCs in the neonate and young child offers greater potential benefits in heart failure treatment than has been realized to date. The second advance is the technology of induced pluripotent stem cells (iPSCs), which reprograms differentiated somatic cells to an undifferentiated embryonic-like state. When iPSCs are differentiated into cardiomyocytes, they model a patient's specific disease, test pharmaceuticals, and potentially provide an autologous source for cell-based therapy. SUMMARY: The therapeutic recruitment and/or replacement of CPCs has potential for enhancing cardiac repair and regeneration in children with heart failure. Use of iPSCs to model heart disease holds great potential to gain new insights into diagnosis, pathophysiology, and disease-specific management for genetic-based cardiovascular diseases that are prevalent in pediatric patients.

Heart cells with regenerative potential from pediatric patients with end stage heart failure: a translatable method to enrich and propagate.

Background. Human cardiac-derived progenitor cells (hCPCs) have shown promise in treating heart failure (HF) in adults. The purpose of this study was to describe derivation of hCPCs from pediatric patients with end-stage HF. Methods. At surgery, discarded right atrial tissues (hAA) were obtained from HF patients (n = 25; hAA-CHF). Minced tissues were suspended in complete (serum-containing) DMEM. Cells were selected for their tissue migration and expression of stem cell factor receptor (hc-kit). Characterization of hc-kit(positive) cells included immunohistochemical screening with a panel of monoclonal antibodies. Results. Cells, including phase-bright cells identified as hc-kit(positive), spontaneously emigrated from hAA-CHF in suspended explant cultures (SEC) after Day 7. When cocultured with tissue, emigrated hc-kit(positive) cells proliferated, first as loosely attached clones and later as multicellular clusters. At Day 21~5% of cells were hc-kit(positive). Between Days 14 and 28 hc-kit(positive) cells exhibited mesodermal commitment (GATA-4(positive) and NKX2.5(positive)); then after Day 28 cardiac lineages (flk-1(positive), smooth muscle actin(positive), troponin-I(positive), and myosin light chain(positive)). Conclusions. C-kit(positive) hCPCs can be derived from atrial tissue of pediatric patients with end-stage HF. SEC is a novel culture method for derivation of migratory hc-kit(positive) cells that favors clinical translation by reducing the need for exogenously added factors to expand hCPCs in vitro.

Initial experience with a multidisciplinary strategy for initiation of propranolol therapy for infantile hemangiomas.

OBJECTIVES: To outline a safe, standardized protocol for outpatient initiation of propranolol therapy for infantile hemangiomas. STUDY DESIGN: Retrospective review. SETTING: Academic tertiary care pediatric hospital. SUBJECTS AND METHODS: Forty-nine infantile hemangioma patients were offered propranolol therapy and included in the study. Any patients requiring hospital admission were excluded. Screening consisted of cardiology evaluation, including electrocardiography and, when indicated, echocardiography. Target initiation dose was 2 to 3 mg/kg/d divided into 3 doses. Blood pressure and heart rate were initially monitored at baseline and 1 and 2 hours in clinic following initial dosing. A 3-hour time point was later added. Families received standardized instructions regarding home heart rate monitoring, side effects, and fasting. RESULTS: Outpatient propranolol therapy was safely initiated in 39 of 44 patients (89%). Five patients required brief admission: 1 with clinical signs/symptoms of heart failure, 3 having airway involvement, and 1 for social reasons. Propranolol administration transiently reduced blood pressure; the maximal decrease occurred at 2 hours, prompting addition of a 3-hour time point to ensure recovery. No patients exhibited symptomatic hypotension, bradycardia, or heart failure. CONCLUSIONS: In most children with infantile hemangiomas, propranolol therapy can be safely initiated as an outpatient. Careful cardiovascular evaluation by an experienced clinician is essential for pretreatment evaluation, inpatient admission (when necessary), blood pressure and heart rate monitoring following initial dosing, and parent education. This standardized multidisciplinary outpatient initiation plan reduces the cost of initiating therapy compared with inpatient strategies while still providing appropriate monitoring for potential treatment complications. Further evaluation of propranolol therapy efficacy at the current dosing and duration of treatment continues.

Innovation in basic science: stem cells and their role in the treatment of paediatric cardiac failure--opportunities and challenges.

Heart failure is a leading cause of death worldwide. Current therapies only delay progression of the cardiac disease or replace the diseased heart with cardiac transplantation. Stem cells represent a recently discovered novel approach to the treatment of cardiac failure that may facilitate the replacement of diseased cardiac tissue and subsequently lead to improved cardiac function and cardiac regeneration. A stem cell is defined as a cell with the properties of being clonogenic, self-renewing, and multipotent. In response to intercellular signalling or environmental stimuli, stem cells differentiate into cells derived from any of the three primary germ layers: ectoderm, endoderm, and mesoderm, a powerful advantage for regenerative therapies. Meanwhile, a cardiac progenitor cell is a multipotent cell that can differentiate into cells of any of the cardiac lineages, including endothelial cells and cardiomyocytes. Stem cells can be classified into three categories: (1) adult stem cells, (2) embryonic stem cells, and (3) induced pluripotential cells. Adult stem cells have been identified in numerous organs and tissues in adults, including bone-marrow, skeletal muscle, adipose tissue, and, as was recently discovered, the heart. Embryonic stem cells are derived from the inner cell mass of the blastocyst stage of the developing embryo. Finally through transcriptional reprogramming, somatic cells, such as fibroblasts, can be converted into induced pluripotential cells that resemble embryonic stem cells. Four classes of stem cells that may lead to cardiac regeneration are: (1) Embryonic stem cells, (2) Bone Marrow derived stem cells, (3) Skeletal myoblasts, and (4) Cardiac stem cells and cardiac progenitor cells. Embryonic stem cells are problematic because of several reasons: (1) the formation of teratomas, (2) potential immunologic cellular rejection, (3) low efficiency of their differentiation into cardiomyocytes, typically 1% in culture, and (4) ethical and political issues. As of now, bone marrow derived stem cells have not been proven to differentiate reproducibly and reliably into cardiomyocytes. Skeletal myoblasts have created in vivo myotubes but have not electrically integrated with the myocardium. Cardiac stem cells and cardiac progenitor cells represent one of the most promising types of cellular therapy for children with cardiac failure.

Carvedilol for children and adolescents with heart failure: a randomized controlled trial.

CONTEXT: Although beta-blockers improve symptoms and survival in adults with heart failure, little is known about these medications in children and adolescents. OBJECTIVE: To prospectively evaluate the effects of carvedilol in children and adolescents with symptomatic systemic ventricular systolic dysfunction. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, double-blind, placebo-controlled study of 161 children and adolescents with symptomatic systolic heart failure from 26 US centers. In addition to treatment with conventional heart failure medications, patients were assigned to receive placebo or carvedilol. Enrollment began in June 2000 and the last dose was given in May 2005 (each patient received medication for 8 months). INTERVENTIONS: Patients were randomized in a 1:1:1 ratio to twice-daily dosing with placebo, low-dose carvedilol (0.2 mg/kg per dose if weight <62.5 kg or 12.5 mg per dose if weight > or =62.5 kg), or high-dose carvedilol (0.4 mg/kg per dose if weight <62.5 kg or 25 mg per dose if weight > or =62.5 kg) and were stratified according to whether each patient's systemic ventricle was a left ventricle or not. MAIN OUTCOME MEASURES: The primary outcome was a composite measure of heart failure outcomes in patients receiving carvedilol (low- and high-dose combined) vs placebo. Secondary efficacy variables included individual components of this composite, echocardiographic measures, and plasma b-type natriuretic peptide levels. RESULTS: There was no statistically significant difference between groups for the composite end point based on the percentage of patients who improved, worsened, or were unchanged. Among 54 patients assigned to placebo, 30 improved (56%), 16 worsened (30%), and 8 were unchanged (15%); among 103 patients assigned to carvedilol, 58 improved (56%), 25 worsened (24%), and 20 were unchanged (19%). The rates of worsening were lower than expected. The odds ratio for worsened outcome for patients in the combined carvedilol group vs the placebo group was 0.79 (95% CI, 0.36-1.59; P = .47). A prespecified subgroup analysis noted significant interaction between treatment and ventricular morphology (P = .02), indicating a possible differential effect of treatment between patients with a systemic left ventricle (beneficial trend) and those whose systemic ventricle was not a left ventricle (nonbeneficial trend). CONCLUSIONS: These preliminary results suggest that carvedilol does not significantly improve clinical heart failure outcomes in children and adolescents with symptomatic systolic heart failure. However, given the lower than expected event rates, the trial may have been underpowered. There may be a differential effect of carvedilol in children and adolescents based on ventricular morphology. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00052026.

Rescue cardiac transplantation for failing staged palliation in patients with hypoplastic left heart syndrome.

OBJECTIVE: Orthotopic heart transplantation is considered a rescue option for children with failing staged palliation or repair of hypoplastic left heart syndrome. We present our strategy for management, and outcomes, for these complex patients. METHODS: We transplanted 68 consecutive children, with diagnoses of hypoplastic left heart syndrome in 31, cardiomyopathy in 20, and post-operative complex congenital heart disease in 17. Of these patients, 9 (13.2%) were neonates, and 46 (67.6%) were infants. Median age was 118.5 days. Operative technique involves bicaval cannulation and anastamoses with continuous low flow bypass, and either short periods of circulatory arrest or continuous low flow antegrade cerebral perfusion for reconstruction of the aortic arch. Initial reperfusion of the donor heart utilizes glutamate and aspartate substrate enriched white blood cell filtered cardioplegia. Immunosuppressive therapy includes induction (pulse steroids, gamma globulin, and polyclonal rabbit antithymocyte globulin) and initial maintenance (calcineurin inhibitor, an anti-proliferative agent, and a weaning steroid protocol). Of the 31 patients with hypoplastic left heart syndrome, 23 underwent primary transplantation, and 8 underwent rescue transplantation from failing staged palliation in seven, or attempted biventricular repair in one. Of the seven patients who had failing staged palliation, three had undergone only the Norwood Stage 1 operation, 2 had undergone a Norwood Stage 1 operation and a Glenn superior cavopulmonary anastomosis and two had undergone a Norwood Stage 1 operation, a Glenn superior cavopulmonary anastomosis, and a completion Fontan operation. RESULTS: The group undergoing primary transplantation was younger (p equals 0.007), weighed less (p equals 0.003), and waited longer for an appropriate donor heart (p equals 0.021) compared to those requiring rescue transplantation. No significant difference exists between the groups with regards to donor heart ischaemic time or post-transplant length of hospital stay. Thirty day survival (p equals 0.156) and overall survival (p equals 0.053) was better in those having primary transplantation, although these differences were not statistically significant when a p value of less than 0.05 is considered to be significant. In those having primary transplantation, no patients had elevated panel reactive antibody greater than 10%. Half of the 8 requiring rescue transplantation had panel reactive antibody greater than 10%, and this subgroup did especially poorly. CONCLUSION: Cardiac transplantation can offer children with failing staged palliation their only chance of survival. Transplantation, however, carries a high risk in this subgroup, especially in the setting of elevated panel reactive antibody.

Initial experience with a bicuspid polytetrafluoroethylene pulmonary valve in 41 children and adults: a new option for right ventricular outflow tract reconstruction.

BACKGROUND: As the population of children with repaired congenital heart disease ages, an increasing number of patients will benefit from pulmonary valve insertion. We report our initial experience in 41 consecutive patients treated with placement of a surgically created polytetrafluoroethylene bicuspid pulmonary valve. METHODS: A bicuspid pulmonary valve with orifice size greater than 24 mm is created with polytetrafluoroethylene and sutured into the right ventricular outflow tract. To obviate the need for reoperation in growing children, this technique is limited to older children and adults. Polytetrafluoroethylene bicuspid pulmonary valves were placed in 41 patients (age: range, 5.0 to 64.7 years, median = 15.7 years; weight: range, 14.2 to 99.0 kilograms, median, 52.0 kg). All patients had pulmonary insufficiency, pulmonary stenosis, or both, after previous intervention for tetralogy of Fallot (27), pulmonary stenosis (11), pulmonary atresia with intact ventricular septum (2), or double outlet right ventricle (1). RESULTS: All patients left the operating theater with transesophageal echocardiography documenting no pulmonic stenosis and zero to trace pulmonic insufficiency. Median hospital length of stay was 5 days (range, 3 to 15 days; mean, 5.8 days). Follow-up including echocardiography ranged from 0.2 to 3.1 year (median follow-up, 1.5 years) and revealed significant improvement in New York Heart Association Classification, pulmonary insufficiency, and right ventricular end diastolic dimension. CONCLUSIONS: Polytetrafluoroethylene bicuspid pulmonary valve reconstruction of the right ventricular outflow tract is a safe, effective, and durable technique for the short term. Appropriate oversizing minimizes outflow tract obstruction while maximizing competence. Long-term follow-up is necessary to determine the true value of this technique.

Pediatric cardiac transplantation in children with high panel reactive antibody.

BACKGROUND: Elevated panel reactive antibody (PRA) may be considered a risk factor precluding pediatric orthotopic heart transplantation. We retrospectively reviewed our management strategy and outcome data for children undergoing heart transplantation with high PRA (> 10%). METHODS: Sixty consecutive children (median age = 130.5 days) underwent heart transplantation. Diagnoses included hypoplastic left heart syndrome (HLHS) (30 patients), cardiomyopathy (18 patients), and postoperative complex congenital heart disease (CCHD) (12 patients). Standard induction immunosuppressive therapy included pulse steroids, gamma globulin, and polyclonal rabbit antithymocyte globulin. Initial immunosuppression is a calcinurin inhibitor and an antiproliferative agent. Eight children exhibited elevated PRA (group P). Fifty-two exhibited nonelevated PRA (group N). Immunosuppression was modified in group P as follows: preoperative intravenous immunoglobulin G (IVIG) and/or cyclophosphamide or mycophenolate mofetil and preoperative and postoperative exchange transfusions or plasmapheresis. In group P, cyclophosphamide was the initial antiproliferative agent. RESULTS: Group P = 4 HLHS patients (all status post [s/p] prior cardiac surgery) and 4 postoperative CCHD patients. Group N = 26 HLHS patients (4 patients s/p prior cardiac surgery), 18 cardiomyopathy patients, and 8 postoperative CCHD patients. Group P patients were older and weighed more than group N patients. Waiting time for donor heart, cardiac ischemic time, and length of hospital stay were similar in both groups. Thirty-day mortality for group P was 25% and for group N it was 7.9% (p = 0.178). Overall mortality for group P was 50% and for group N it was 15.4% (p = 0.043). CONCLUSIONS: Although heart transplantation can offer children with end-stage heart failure and elevated PRA their only chance of survival, these patients remain high risk despite aggressive immunosuppression.