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Background Failure to thrive (FTT), defined as weight or height less than the lowest 2.5 percentile for age, is prevalent in up to 66% of children with congenital heart disease (CHD). Risk stratification methods to identify those who would benefit from early intervention are currently lacking. We aimed to identify a novel growth biomarker to aid clinical decision-making in children with CHD. Methods This is a cross-sectional study of patients 2 months to 10 years of age with any CHD undergoing cardiac surgery. Preoperative weight-for-age Z scores (WAZ) and height-for-age Z scores (HAZ) were calculated and assessed for association with preoperative plasma biomarkers: growth differentiation factor 15 (GDF-15), fibroblast growth factor 21, leptin, prealbumin, and C-reactive protein (CRP). Results Of the 238 patients included, approximately 70% of patients had WAZ/HAZ < 0 and 34% had FTT. There was a moderate correlation between GDF-15 and WAZ/HAZ. When stratified by age, the correlation of GDF-15 to WAZ and HAZ was strongest in children under 2 years of age and persisted in the setting of inflammation (CRP > 0.5 mg/dL). Diagnoses commonly associated with congestive heart failure had high proportions of FTT and median GDF-15 levels. Prealbumin was not correlated with WAZ or HAZ. Conclusions GDF-15 represents an important growth biomarker in children with CHD, especially those under 2 years of age who have diagnoses commonly associated with CHF. Our data do not support prealbumin as a long-term growth biomarker.

Background:Obesity increases the risk of post-operative arrhythmias in adults undergoing cardiac surgery, but little is known regarding the impact of obesity on post-operative arrhythmias after CHD surgery.Methods:Patients undergoing CHD surgery from 2007 to 2019 were prospectively enrolled in the parent study. Telemetry was assessed daily, with documentation of all arrhythmias. Patients aged 2–20 years were categorised by body mass index percentile for age and sex (underweight 95). Patients aged >20 years were categorised using absolute body mass index. We investigated the impact of body mass index category on arrhythmias using univariate and multivariate analysis.Results:There were 1250 operative cases: 12% underweight, 65% normal weight, 12% overweight, and 11% obese. Post-operative arrhythmias were observed in 38%. Body mass index was significantly higher in those with arrhythmias (18.8 versus 17.8, p = 0.003). There was a linear relationship between body mass index category and incidence of arrhythmias: underweight 33%, normal 38%, overweight 42%, and obese 45% (p = 0.017 for trend). In multivariate analysis, body mass index category was independently associated with post-operative arrhythmias (p = 0.021), with odds ratio 1.64 in obese patients as compared to normal-weight patients (p = 0.036). In addition, aortic cross-clamp time (OR 1.007, p = 0.002) and maximal vasoactive–inotropic score in the first 48 hours (OR 1.03, p = 0.04) were associated with post-operative arrhythmias.Conclusion:Body mass index is independently associated with incidence of post-operative arrhythmias in children after CHD surgery.

As a result of improvements in care for patients with congenital heart disease (CHD), >90% of children born with CHD are expected to survive to adulthood. For those adults, heart failure (HF) is the leading cause of death. Advances in recognition of, and treatments for, these patients continue to improve. Specifically, adults with CHD are candidates for both heart transplantation and mechanical circulatory support. However, challenges remain that require investigation to improve outcomes.

We present a case report of severed epicardial atrial lead salvage using an IS-1 lead extender. A 37-year-old male with single ventricle physiology, Fontan palliation, sinus node dysfunction, recurrent atrial tachycardias, and atrial fibrillation resulting in failing Fontan physiology presented with failure of the atrial pacing lead. The patient was initially paced with an epicardial system that had to be removed due to pocket infection, and the epicardial leads were cut and abandoned. Given his significant sinus node dysfunction he required atrial pacing to allow for rhythm control. The failing Fontan physiology of the patient precluded him from undergoing surgery for epicardial lead placement or a complex intravascular lead placement procedure (although anatomically feasible). We considered the option of salvaging the existing epicardial atrial leads to provide atrial pacing, allowing for rhythm control and improvement of his failing Fontan physiology as a bridge to a more permanent pacing solution. This case report is important because it demonstrates how a lead extender can be used to salvage a severed pacemaker lead. This may be useful for patients in whom implantation of new leads is not promptly feasible due to patient anatomy and/or clinical status.

A 49-year-old female with congenitally corrected (or levo-) transposition of the great arteries complicated by nonischemic cardiomyopathy presented for worsening heart failure despite guideline-directed medical therapy and was found to be in cardiogenic shock. She successfully underwent ventricular assist device placement with a HeartMate III to her systemic right ventricle as a bridge to transplantation.

We report the case of a 9-month-old male with Williams syndrome who underwent patch augmentation of supravalvar aortic stenosis and pulmonary artery stenosis, and required emergent drug-eluting left coronary artery stenting on post-operative day 1 for severe left ventricular dysfunction related to myocardial ischemia.

There are limited published data addressing the costs associated with pediatric heart transplantation and no studies evaluating the variation in costs across centers. We aimed to describe center variation in pediatric heart transplant costs and assess the association of transplant hospitalization costs with patient outcomes. Using a linkage between the Pediatric Health Information System and Scientific Registry of Transplant Recipients databases, hospital costs were assessed for patients (

BACKGROUND Despite significant changes in the past decade for children undergoing heart transplantation, including the evolution of mechanical circulatory support and increasing patient complexity, costs and resource utilization have not been reassessed. We sought to use a novel linkage of clinical-registry and administrative data to examine changes in hospitalization costs over time in this population. METHODS We identified all pediatric heart transplant recipients in a unique linked Pediatric Health Information System/Scientific Registry of Transplant Recipients data set (2002-2016). Hospital costs were estimated from charges using cost-to-charge ratios, inflated to 2016 dollars. Severity-adjusted costs were calculated using generalized linear mixed-effects models. Costs were compared across 3 eras (era 1, 2002-2006; era 2, 2007-2011; and era 3, 2012-2016). RESULTS A total of 2896 pediatric heart transplant recipients were included: era 1, 649 (22.4%); era 2, 1028 (35.5%); and era 3, 1219 (42.1%). Extracorporeal membrane oxygenation support at transplant decreased over time, concurrent with an increase in ventricular assist device-supported patients. Between era 1 and era 2, there was an increase in pretransplant hospitalization costs (US $343 692 vs US $435 554; P < 0.001). However, between era 2 and era 3, there was a decline in total (US $906 454 vs US $767 221; P < 0.001), pretransplant (US $435 554 vs US $353 364; P < 0.001), and posttransplant (US $586 133 vs US $508 719; P = 0.002) hospitalization costs. CONCLUSIONS Concurrent with the increase in utilization of ventricular assist device support, there has been an increase in pretransplant costs associated with pediatric heart transplantation. However, in the most recent era, costs have declined. These findings suggest the evolution of more cost-effective management strategies, which may be related to shifts in the approach to pediatric mechanical circulatory support.

Background: Many pediatric heart transplant recipients live a significant distance from their transplant center. This results in families either traveling long distances or relying on outside physicians to assume aspects of their care. Distance has been implicated to play a role in congenital heart disease outcomes, but its impact on heart transplantation has not been reported. The aim of this study was to assess the impact of distance on pediatric heart transplant outcomes. Methods: The Scientific Registry of Transplant Recipients database was queried for all pediatric heart transplant recipients from large US children’s hospitals (1987-2014). Patients were stratified into 4 groups (100 miles) based on distance. Survival curves were generated and compared using the log-rank test. Cox proportional hazards regression was performed to adjust for differences between groups. Results: A total of 4768 patients were included in the analysis, of which 1435 (30.1%) were 100 miles from their transplant center. There was no difference in posttransplant survival based on distance after adjusting for patient age, gender, ethnicity, blood type, diagnosis, listing status, and the need for pretransplant ventricular assist device, extracorporeal membrane oxygenation, or ventilator support. Conclusion: There is no significant difference in graft survival after pediatric heart transplantation based on patient distance from their transplant center. Our data suggest the current strategy of transitioning some aspects of transplant care to local physicians or management from a distance does not increase posttransplant mortality risk.

Background Transplant-free survival for single right ventricle (RV) lesions remains less than 70% at 3 years. Arrhythmia burden, influence of shunt type at Norwood procedure (RV-to-pulmonary artery shunt [RVPAS] versus Blalock-Taussig shunt [BTS]), and implications for mortality risk are not well defined. Methods The authors performed a single-center retrospective analysis of patients with single RV lesions enrolled in a prospective study of arrhythmias after congenital heart surgery. Results Fifty-eight patients received a RVPAS and 62 received a BTS, with a median follow-up of 773 days. Overall arrhythmia incidence was 78%, two-thirds of which prompted intervention. Among all types of arrhythmias, only ventricular arrhythmias (VAs) differed by shunt type, which were more common in patients receiving an RVPAS (29% RVPAS versus 14% BTS; p = 0.049). The majority of VAs were transient (69% less than 1 minute), and typically occurred early post-Norwood procedure (median 12 days). No additional variables were associated with development of VAs. Shunt type did not influence transplant-free survival. Within the entire cohort, there was a trend toward increased mortality with prior history of VA (odds ratio, 2.90; 95% confidence interval, 0.99 to 8.90; p = 0.052). For interstage survivors to Glenn palliation, any VA associated with a 14-fold increased risk of death or transplant (hazard ratio, 14.00; 95% confidence interval, 3.66 to 53.40; p .001). No other tachyarrhythmia or bradyarrhythmia was associated with mortality. Conclusions In this cohort with single RV lesions and prospective rhythm surveillance, patients receiving an RVPAS at Norwood surgery had an increased incidence of VAs compared with patients with a BTS. VAs correlated with late mortality in patients who survived the interstage period.

Background Large clinical, research, and administrative databases are increasingly utilized to facilitate pediatric heart transplant (HTx) research. Linking databases has proven to be a robust strategy across multiple disciplines to expand the possible analyses that can be performed while leveraging the strengths of each dataset. We describe a unique linkage of the Scientific Registry of Transplant Recipients (SRTR) database and the Pediatric Health Information System (PHIS) administrative database to provide a platform to assess resource utilization in pediatric HTx. Methods All pediatric patients (1999-2016) who underwent HTx at a hospital enrolled in the PHIS database were identified. A linkage was performed between the SRTR and PHIS databases in a stepwise approach using indirect identifiers. To determine the feasibility of using these linked data to assess resource utilization, total and post-HTx hospital costs were assessed. Results A total of 3188 unique transplants were identified as being present in both databases and amenable to linkage. Linkage of SRTR and PHIS data was successful in 3057 (95.9%) patients, of whom 2896 (90.8%) had complete cost data. Median total and post-HTx hospital costs were $518,906 (IQR $324,199-$889,738), and $334,490 (IQR $235,506-$498,803) respectively with significant differences based on patient demographics and clinical characteristics at HTx. Conclusions Linkage of the SRTR and PHIS databases is feasible and provides an invaluable tool to assess resource utilization. Our analysis provides contemporary cost data for pediatric HTx from the largest US sample reported to date. It also provides a platform for expanded analyses in the pediatric HTx population.

To assess the prevalence of psychiatric disorders and associated therapies in children during their heart transplantation admission.All pediatric heart transplant recipients (1999-2016) were included from a linked administrative and clinical registry database. Psychiatric disorders and associated therapies were identified using International Classification of Diseases or billing codes during the transplant admission. Data were analyzed using standard descriptive statistics. Multivariable logistic regression assessed factors independently associated with psychiatric disorders or therapies.A total of 3073 pediatric heart transplant recipients were included. Psychiatric disorders were present in 434 (14.1%) patients during the heart transplant admission, with adjustment disorders being the most common. Antidepressant therapy was prescribed to 212 patients (6.9%) and selective serotonin reuptake inhibitors were most commonly used. Psychiatric diagnoses (8.4% vs 18.1%; P .001) and the use of antidepressants (4.5% vs 8.9%; P .001) increased over time (era 1, 1999-2009 vs era 2, 2010-2016). Psychiatric disorders were present in 39.8% of patients ≥8 years of age requiring ventricular assist device support at heart transplantation. The need for ventricular assist device support was independently associated with psychiatric diagnoses (aOR, 1.57; 95% CI, 1.18-2.1; P = .002) and antidepressant therapy (aOR, 2.11; 95% CI. 1.43-3.12; P .001).Psychiatric disorders are common in pediatric heart transplant recipients, especially among those bridged with ventricular assist device support. Psychiatric diagnoses and the use of antidepressants has increased over time, likely representing improved recognition of psychiatric comorbidities in this vulnerable population. Access to psychiatric services represents an important component of the multidisciplinary team caring for pediatric heart transplant recipients.

Primary graft dysfunction following heart transplantation (HTx) is associated with significant morbidity and mortality. This study aimed to assess the incidence of, risk-factors for, and outcomes of children requiring ECMO within 24-hours of HTx. This study utilized a linked PHIS/SRTR database of pediatric HTx recipients (2002–2016). Post-HTx ECMO was identified using inpatient billing data. Logistic regression assessed risk-factors for post-HTx ECMO. Kaplan-Meier analyses assessed in-hospital mortality and post-discharge survival. A total of 2,820 patients were included with 224 (7.9%) requiring ECMO. Independent risk-factors for post-HTx ECMO include age

Background Pediatric patients with atrioventricular valve disease have limited options for prosthetic valve replacement in sizes Methods and Results A multicenter, retrospective cohort study was performed among patients who underwent atrioventricular valve replacement with Melody valve at 17 participating sites from North America and Europe, including 68 patients with either mitral (n=59) or tricuspid (n=9) replacement at a median age of 8 months (range, 3 days to 13 years). The median size at implantation was 14 mm (range, 9–24 mm). Immediately postoperatively, the valve was competent with low gradients in all patients. Fifteen patients died; 3 patients underwent transplantation. Nineteen patients required reoperation for adverse outcomes, including valve explantation (n=16), left ventricular outflow tract obstruction (n=1), permanent pacemaker implantation (n=1), and paravalvular leak repair (n=1). Twenty-five patients underwent 41 episodes of catheter-based balloon expansion, exhibiting a significant decrease in median gradient ( P Conclusions The Melody valve is a feasible option for surgical atrioventricular valve replacement in patients with hypoplastic annuli. The prosthesis shows acceptable short-term function and is amenable to catheter-based enlargement as the child grows. However, patients remain at risk for mortality and structural valve deterioration, despite adequate early valvular function. Device design and implantation techniques must be refined to reduce complications and extend durability. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02505074.

BACKGROUND The number of adult congenital heart disease (ACHD) patients requiring heart transplantation (HT) continues to grow, and if they survive the first year after transplant, their long-term survival is at least equivalent to non-ACHD patients. The 1-year survival of ACHD patients with HT remains lower than non-ACHD patients. We evaluated the affect of transplant center volume on 1-year survival of ACHD patients. We analyzed United Network of Organ Sharing patients (age ≥18 years) who underwent their first orthotopic HT between January 1, 2000, and December 31, 2015, to assess the association between transplant center volume and 1-year survival of ACHD patients. RESULTS We identified 827 ACHD patients at 113 centers who underwent HT during the study period. The average age of the recipients and donors was 36 ± 13 years (60% men and 84% Caucasian) and 28 ± 11 (63% men and 66% Caucasian), respectively. Of the ACHD patients undergoing HT, 27% (n = 60) were done at low-volume centers, 30% (n = 10) were reported at high-volume centers, and the remaining (n = 43) were at medium-volume centers. A total of 96 patients died within 30 days, including 37 (16.7%) at low-volume, 37 (10.2%) at medium-volume, and 22 (9.0%) at high-volume centers (p = 0.019). The average unadjusted Kaplan-Meier 30-day survival at low-volume centers was 83% ± 2%, which was significantly lower than medium-volume (90% ± 1%) and high-volume (91% ± 2%) centers (log-rank p < 0.05). Within 1 year, 154 patients had died, including 56 (36.4%) at low-volume, 60 (38.9%) at medium-volume, and 38 (24.7%) at high-volume centers (p = 0.011). Average unadjusted Kaplan-Meier 1-year survival at low-volume centers was 75% ± 3%, which was significantly lower than medium-volume (83% ± 2%) and high-volume (84% ± 2%) centers (log-rank p < 0.05). CONCLUSIONS The 30-day and 1-year survival of ACHD patients undergoing HT is partly influenced by overall transplant center volume and, potentially, volume of ACHD HTs, with low-volume centers performing poorly relative to medium-volume and high-volume centers. The role of peri-operative care and multidisciplinary management in improving survival at low-volume centers required further investigations.

Purpose Orthotopic heart transplantation (OHT) among adult congenital heart disease (ACHD) patients triggers debate as to optimal donor sizing. Outcomes related to donor-to-recipient size ratios have never been analyzed in the ACHD population. Methods We conducted a retrospective cohort analysis of adults with ACHD undergoing OHT in the USA from January 1, 2000 to June 30, 2017 using the United Network for Organ Sharing (UNOS) registry. Univariate and multivariate analyses were performed to compare survivors versus those deceased at last follow-up. Chi-squared and Wilcoxon rank sum tests were used for categorical and continuous variables, respectively. Cox proportional hazard modeling was performed for time to death, cardiac graft failure, and post-OHT dialysis to assess the effects of donor-to-recipient ratios of height, weight, BMI, and LV mass ratios using a priori selected covariates. Results 827 patients met inclusion criteria and were analyzed. At a median follow-up of 1,462 days, there were 279 (33.7%) deceased ACHD OHT recipients. Renal dysfunction, ischemic time , and gender mismatch were all significantly associated with death and graft dysfunction using multivariate survival analysis. However, donor-to-recipient ratios of height, weight, BMI, and LV mass were not associated with the outcomes of interest. Conclusion This study is the first to show that ACHD patients undergoing OHT do not have differential survival based on donor sizing. Survival and freedom from graft dysfunction among ACHD patients undergoing OHT is similar to the non-ACHD population and is associated with reduced ischemic times, a lack of gender mismatch, and a lack of pre- and post-operative renal dysfunction. Our findings demonstrate that intentional donor oversizing in the ACHD population as a protective measure against post-operative right ventricular dysfunction does not reduce mortality, decrease risk of graft dysfunction or post-OHT need for dialysis.

Bleeding and thrombosis are well-known potential complications of VAD support. We present a pediatric patient who developed massive bilateral pulmonary emboli while on BiVAD support that was successfully treated with intravenous tPA and bridged to heart transplant.

BACKGROUND: Pediatric mechanical circulatory support (MCS) has evolved considerably over the past decade. Though marked improvements in waitlist survival have been realized, costs have not been reassessed. This project aimed to assess contemporary MCS costs in children bridged to heart transplant (HT). METHODS: All pediatric HT recipients (2002–2016) were identified from a unique, linked PHIS/SRTR dataset. Costs were calculated from hospital charges, inflated to 2016 Dollars and adjusted for patient-specific characteristics using generalized linear mixed-effects models. Costs and length of stay (LOS) were compared across support strategies at the time of HT (no MCS, VAD, or ECMO) with select subgroup analyses. RESULTS: A total of 2873 pediatric HT recipients were included; no MCS: 2268 (78.9%), VAD: 470 (16.4%), and ECMO: 135 (4.7%). Both VAD and ECMO were associated with greater total hospitalization costs compared to no MCS ($755,345 and $808,771 vs. $457,086; p

There is controversy regarding the management of projectile embolization, a rare complication of penetrating trauma. We present the case of a 5-year-old, 20 kg male with retrograde venous projectile embolization following traumatic injury with a pellet gun. The projectile was successfully removed utilizing a novel, percutaneous approach.

Background Despite resource burdens associated with hospital readmission, there remains little multiinstitutional data available to identify children at risk for readmission following congenital heart surgery. Methods and Results Children undergoing congenital heart surgery and discharged home between January of 2011 and December 2012 were identified within the Pediatric Health Information System database, a multiinstitutional collection of clinical and administrative data. Patient discharges were assigned to derivation and validation cohorts for the purposes of predictive model design, with 17 871 discharges meeting inclusion criteria. Readmission within 30 days was noted following 956 (11%) of discharges within the derivation cohort (n = 9104), with a median time to readmission of 9 days (interquartile range [IQR] 5–18 days). Readmissions resulted in a rehospitalization length of stay of 4 days (IQR 2–8 days) and were associated with an intensive care unit (ICU) admission in 36% of cases. Independent perioperative predictors of readmission included Risk Adjustment in Congenital Heart Surgery score of 6 (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.8–3.7, P < .001) and ICU length of stay of at least 7 days (OR 1.9 95% CI 1.6–2.2, P < .001). Demographic predictors included Hispanic ethnicity (OR 1.2, 95% CI 1.1–1.4, P = .014) and government payor status (OR 1.2, 95% CI 1.1–1.4, P = .007). Predictive model performance was modest among validation cohort (c statistic 0.68, 95% CI 0.66–0.69, P < .001). Conclusions Readmissions following congenital heart surgery are common and associated with significant resource consumption. While we describe independent predictors that may identify patients at risk for readmission prior to hospital discharge, there likely remains other unreported factors that may contribute to readmission following congenital heart surgery.

Purpose Primary graft dysfunction following heart transplantation (HT) is associated with significant morbidity and mortality. The aim of this study was to assess the incidence, risk factors, and outcomes of pediatric patients requiring extracorporeal membrane oxygenation (ECMO) support post-HT. Methods This study utilized an existing data linkage between the PHIS and SRTR databases from which pediatric HT recipients were identified (2002-2016). Post-HT ECMO support was identified by billing codes within one day of HT. Logistic regression was performed to assess risk factors for ECMO post-HT. Kaplan-Meier analyses assessed in-hospital mortality and post-discharge survival. Results A total of 2,820 patients were included with 224 (7.9%) requiring ECMO post-HT. Risk factors independently associated with the need for ECMO included age Conclusion There are identifiable risk factors associated with the need for ECMO in the post-HT period. Length of time on ECMO post-HT is strongly associated with the risk of in-hospital mortality. While patients who require ECMO post-HT demonstrate worse overall survival, those who survive to discharge have comparable outcomes to patients who did not require ECMO.

Background Neonatal aortic arch reconstruction, typically performed with deep hypothermia and selective cerebral perfusion, leaves splanchnic organ protection dependent on hypothermia alone. A simplified method of direct in-field descending aortic perfusion during neonatal arch reconstruction permits the avoidance of deep hypothermia. We hypothesize that direct splanchnic perfusion at mild hypothermia provides improved or equivalent safety compared with deep hypothermia and may contribute to postoperative extracardiac organ recovery. Methods Included were 138 biventricular patients aged younger than 90 days undergoing aortic arch reconstruction with cardiopulmonary bypass. Patients were grouped according to perfusion method A (selective cerebral perfusion with deep hyperthermia at 18° to 20°C) or method B (selective cerebral perfusion and splanchnic perfusion at 30° to 32°C). Patient characteristics and perioperative clinical and serologic data were analyzed. Significance was assigned for p of less than 0.05. Results Of the 138 survivors, 63 underwent method A and 75 underwent method B. The median age at operation was 8.5 days (range, 6 to 15 days), and median weight was 3.2 kg (range, 2.8 to 3.73 kg), with no significant differences between groups. Cardiopulmonary bypass times were comparable between the two perfusion methods ( p = 0.255) as were the ascending aortic cross-clamp times ( p = 0.737). The postoperative glomerular filtration rate was significantly different between our groups ( p = 0.028 to 0.044), with method B achieving a higher glomerular filtration rate. No significant differences were seen in ventilator time, postoperative length of stay, fractional increase of postoperative serum creatinine over preoperative serum creatinine, and postoperative lactate. Conclusions A simplified method of direct splanchnic perfusion during neonatal aortic arch reconstruction avoids the use of deep hypothermia and provides renal protection at least as effective as deep hypothermia.

The use of status exceptions (SE) was recently publicized as a strategy to reduce waitlist times for children awaiting heart transplant (HTx). The aim of this study was to assess SE use across UNOS regions and compare survival in patients listed using a SE to those listed by standard criteria. The OPTN database was queried for all pediatric patients listed for HTx (2000–2014). SE use was compared across UNOS regions. Survival curves were generated and compared using the log-rank test. 1A SE use is uncommon, being utilized in 108 of 4587 pediatric 1A listings (2.4%). There is significant variability in SE use across UNOS regions (0.7%–16.4% of 1A listings, P

There are limited published data on pediatric organ donation rates. The aim of this study was to describe the trends in pediatric organ donation over time and to assess the regional variation in pediatric deceased organ donation. OPTN data were utilized to assess the trends in pediatric organ donation over time. The number of deceased pediatric organ donors was indexed using regional mortality data obtained from the National Center for Health Statistics and compared across UNOS regions and two different eras. The number of pediatric deceased organ donors has declined in the recent era, largely driven by fewer adolescent donors. For all age groups, there is significant regional variation in organ donation rates, with identifiable high- and low-performing regions. Expansion of the donor pool may be possible by optimizing organ donation in regions demonstrating lower recruitment of pediatric donors. Using the region with the highest donation rate for each age group as the gold standard, we estimate a potential 24% increase in the number of donors if all regions performed comparably, equating to 215 new pediatric donors annually.

Background Workforce estimates suggest 11% of general surgery residents are considering careers in cardiothoracic (CT) surgery. In an effort to identify areas for programmatic improvement, we examined trends in thoracic surgery residents' perspectives on training and employment. Methods Results from the 2010 Thoracic Surgery Residents Association workforce survey were analyzed. The survey was administered to all trainees in North America during the annual in-service exam. Longitudinal trends from 2006 to 2010 are reported. Results Of 299 respondents, 76% (228 of 299) were US citizens. The most common determinants in choosing CT surgery were types of cases (123 of 299, 41%) and mentorship (95 of 299, 32%). Sixty-five percent (193 of 299) would recommend CT surgery to potential trainees. While 81% (242 of 299) felt they would be adequately trained in their program, 39% (118 of 299) planned additional fellowship training. Only 23% (70 of 299) felt the 80-hour work week had a positive impact on training. Of residents seeking jobs, 68% (62 of 92) received 2 or more job interviews and 70% (69 of 99) more than 1 job offer. Seventeen percent (16 of 92) had no offers. While 45% (51 of 114) reported still searching for employment, 20% (23 of 114) had accepted private practice positions, 25% (29 of 114) academic positions, and 6% (7 of 114) fellowship positions. Education-related debt was greater than $100,000 in 46% (140 of 299) and greater than $200,000 in 17% (52 of 299). From 2007 to 2010, CT residents reporting debt greater than $200,000 rose from 8% to 17%. Accepted fellowship training positions dropped to 6% in 2010 compared with 13% and 15% in 2008 and 2009, respectively. Conclusions Diminished CT job opportunities remain a concern. There are concerning trends in debt accrual and perceptions of work-hour restrictions on quality of training. These data justify further investigation into areas of improvement in CT training.

Background Reconstruction of the right ventricular outflow tract is a frequently encountered component of many congenital cardiac repairs. We sought to tissue engineer pulmonary artery augmentation patches from retrovirally labeled endothelial progenitor and mesenchymal stem cells and determine the persistence of the seeded cells in vivo. Methods Autologous ovine endothelial progenitor and mesenchymal stem cells were labeled with a retroviral vector encoding green and red fluorescent proteins, coseeded onto biopolymers, and cultured for 5 days. The tissue-engineered patches were implanted into the main pulmonary artery with 1, 2, 4, and 6 week in vivo maturation (n = 8). In vivo evaluation included ultrasonography and angiography, with preimplant and explanted specimens evaluated using histologic examination and immunofluorescence. Results Echocardiography at each time demonstrated laminar pulmonary artery flow without a pressure gradient across the replaced segment. Pulmonary angiography did not exhibit stenosis or aneurysmal change. Gross appearance of all explanted patches showed progressive tissue formation with increased length of time in vivo. Retrovirally labeled cellular persistence was 96%, 82%, 85%, and 66% at 1, 2, 4, and 6 weeks after implantation, respectively. Early in the in vivo remodeling period, the number of green fluorescent protein–positive endothelial progenitor cells was 1.6 fold greater than the red fluorescent protein–positive mesenchymal stem cells. As in vivo remodeling continued, red fluorescent protein–expressing mesenchymal stem cells were expressed 1.2 to 1.7 times that of the green fluorescent protein–positive endothelial progenitor cells. Conclusions The data demonstrate the successful creation of an anatomically functional, autologous tissue-engineered pulmonary artery using coseeded progenitor cell sources. Labeled implanted stem cells persisted in the engineered construct, suggesting that in vitro seeding is necessary to engineer tissue. This study demonstrates an effective method to track multiple cell types after implantation.

An unresolved question regarding tissue-engineered (TE) cardiac valves and vessels is the fate of the transplanted cells in vivo. We have developed a strategy to track the anatomic location of seeded cells within TE constructs and neighboring tissues using a retroviral vector system encoding green and red fluorescent proteins (GFPs and RFPs, respectively) in ovine circulating endothelial progenitor cells (EPCs) and bone marrow-derived mesenchymal stem cells (BMSCs). We demonstrate that stable transduction ex vivo with high-titer Moloney murine leukemia virus-based retroviral vector yields transduction efficiency of greater than 97% GFP(+) EPC- and RFP(+) mesenchymal stem cell (MSC)-derived cells. Cellular phenotype and transgene expression were also maintained through 25 subsequent passages. Using a retroviral vector system to distinguish our pre-seeded cells from tissue-resident progenitor cells and circulating endothelial and marrow-derived precursors, we simultaneously co-seeded 2 x 10(6) GFP(+) EPCs and 2 x 10(5) RFP(+) MSCs onto the TE patches. In a series of ovine pulmonary artery patch augmentation studies, transplanted GFP(+) EPC- and RFP(+) MSC-derived cells persisted within the TE patch 7 to 14 days after implantation, as identified using immunofluorescence. Analysis showed 81% luminal coverage of the TE patches before implantation with transduced cells, increasing to 96% at day 7 and decreasing to 67% at day 14 post-implantation. This suggests a temporal association between retroviral expression of progenitor cells and mediating effects of these cells on the physiological remodeling and maturation of the TE constructs. To our knowledge, this is the first cardiovascular tissue-engineering in vivo study using a double-labeling method to demonstrate a direct evidence of the source, persistence, and incorporation into a TE vascular patch of co-cultured and simultaneously pre-seeded adult progenitor cells.

Background/Purpose Patients with hypoplastic left heart syndrome (HLHS) experience a higher risk for complications from gastroesophageal reflux, prompting frequent need for fundoplication. Patients between stage I and II palliation ("interstage") are at particularly high operative risk because of the parallel nature of their pulmonary and systemic blood flow. Laparoscopic approach for fundoplication is common for pediatric patients. However, its safety in interstage HLHS is relatively unknown. We examined the perioperative physiologic burden of a laparoscopic fundoplication in HLHS patients. Methods All patients who underwent open or laparoscopic fundoplication during the interstage period at our institution since 2006 were reviewed. Perioperative physiologic data, echocardiographic findings, survival, and complications were collected from the anesthetic record and patient chart. Results Nineteen patients with HLHS had laparoscopic fundoplication, 13 (68%) during the interstage period, compared to 64 performed by the open approach. Ten (77%) of 13 interstage patients had perioperative hemodynamic instability. Incidence of instability between open and laparoscopic groups was not different. One laparoscopic patient required ECMO support for shunt thrombosis. Conclusions Despite a high incidence of hemodynamic instability, overall outcomes are consistent with those reported in the literature for this high-risk patient population. Laparoscopic approach for fundoplication during the interstage period appears to be a relatively safe option for these patients.

The bidirectional Glenn (BDG) procedure involves the anastomosis of the superior vena cava (SVC) to the pulmonary artery, increasing central venous pressure (CVP). We hypothesize that this increase in CVP triggers an acute neurologic insult, leading to ventriculomegaly. In this retrospective analysis in a tertiary care children’s hospital, we identified 167 patients who underwent the BDG procedure between August 2006 and July 2013. Within this initial cohort, 24 patients had head imaging (CT, MRI, or ultrasound) performed both before and after the BDG. From head imaging available from these 24 patients, we measured the frontal-occipital horn ratio (FOR), a well-validated measure of lateral ventricle size. Using central venous catheter data, we assessed postoperative CVP at 12, 24, and 48 h. Paired t tests and linear regression were used to evaluate our cohort. Median age at surgery was 4.9 months. Paired analysis revealed that median FOR significantly increased between preoperative (median 0.38, IQR 0.37–0.41) and postoperative (median 0.42, IQR 0.40–0.45) head images (p = 0.005). Increasing change in FOR was associated with increased 12-h (R 2 = 0.369, p = 0.003) but not 24- or 48-h postoperative CVP. To our knowledge, our study is the first to demonstrate ventriculomegaly developing after the BDG. Physiologically, increasing CVP after the BDG was associated with greater change in lateral ventricle size. This supports the contention that increasing CVP produced during the BDG may damage the developing brain. This study has informed a prospective evaluation of a link between the BDG procedure and neurologic outcomes.

ObjectiveAprotinin is a serine protease inhibitor used during cardiac surgery to reduce blood loss and preserve platelet function. It has also been shown to reduce leukocyte activation during and after cardiopulmonary bypass. The goal of the study was to test the hypothesis that aprotinin could reduce cerebral injury after low-flow cardiopulmonary bypass and deep hypothermic circulatory arrest.MethodsSixteen piglets (mean weight, 13.6 ± 1.3 kg) were randomly assigned to receive aprotinin or placebo (8 animals per group) before a 120-minute period of deep hypothermic circulatory arrest (15°C) or 25 mL · kg−1 · min−1 low-flow cardiopulmonary bypass (25°C or 34°C). Piglets had a cranial window placed over the parietal cerebral cortex for direct examination of the microcirculation by means of intravital microscopy. Rhodamine-stained leukocytes were observed in postcapillary venules, with analysis for adhesion and rolling. Plasma was labeled with fluorescein isothiocyanate–dextran for assessment of functional capillary density. Neurologic and histologic scores were used as the primary outcome measures.ResultsDuring rewarming, the mean number of both rolling and adherent leukocytes was significantly lower after aprotinin administration (P < .05). At 5 and 15 minutes of rewarming, functional capillary density recovered faster with aprotinin treatment (P < .05). Functional outcome (neurologic deficit score) on postoperative day 1 was significantly improved in aprotinin-treated piglets (P < .05).ConclusionsAprotinin reduces inflammation and improves neurologic outcome after a prolonged period of deep hypothermic circulatory arrest or low-flow cardiopulmonary bypass.

Heart valve disease is a significant medical problem worldwide. Current treatment for heart valve disease is heart valve replacement. State of the art replacement heart valves are less than ideal and are associated with significant complications. Using the basic principles of tissue engineering, promising alternatives to current replacement heart valves are being developed. Significant progress has been made in the development of a tissue-engineered semilunar heart valve substitute. Advancements include the development of different potential cell sources and cell-seeding techniques; advancements in matrix and scaffold development and in polymer chemistry fabrication; and the development of a variety of bioreactors, which are biomimetic devices used to modulate the development of tissue-engineered neotissue in vitro through the application of biochemical and biomechanical stimuli. This review addresses the need for a tissue-engineered alternative to the current heart valve replacement options. The basics of heart valve structure and function, heart valve disease, and currently available heart valve replacements are discussed. The last 10 years of investigation into a tissue-engineered heart valve as well as current developments are reviewed. Finally, the early clinical applications of cardiovascular tissue engineering are presented.

Objective Hemolysis, occurring during cardiopulmonary bypass, is associated with lipid peroxidation and postoperative acute kidney injury. Acetaminophen inhibits lipid peroxidation catalyzed by hemeproteins and in an animal model attenuated rhabdomyolysis-induced acute kidney injury. This pilot study tests the hypothesis that acetaminophen attenuates lipid peroxidation in children undergoing cardiopulmonary bypass. Design Single-center prospective randomized double-blinded study. Setting University-affiliated pediatric hospital. Patients Thirty children undergoing elective surgical correction of a congenital heart defect. Interventions Patients were randomized to acetaminophen (OFIRMEV [acetaminophen] injection; Cadence Pharmaceuticals, San Diego, CA) or placebo every 6 hours for four doses starting before the onset of cardiopulmonary bypass. Measurement and main results Markers of hemolysis, lipid peroxidation (isofurans and F2-isoprostanes), and acute kidney injury were measured throughout the perioperative period. Cardiopulmonary bypass was associated with a significant increase in free hemoglobin (from a prebypass level of 9.8 ± 6.2 mg/dL to a peak of 201.5 ± 42.6 mg/dL postbypass). Plasma and urine isofuran and F2-isoprostane concentrations increased significantly during surgery. The magnitude of increase in plasma isofurans was greater than the magnitude in increase in plasma F2-isoprostanes. Acetaminophen attenuated the increase in plasma isofurans compared with placebo (p = 0.02 for effect of study drug). There was no significant effect of acetaminophen on plasma F2-isoprostanes or urinary makers of lipid peroxidation. Acetaminophen did not affect postoperative creatinine, urinary neutrophil gelatinase-associated lipocalin, or prevalence of acute kidney injury. Conclusion Cardiopulmonary bypass in children is associated with hemolysis and lipid peroxidation. Acetaminophen attenuated the increase in plasma isofuran concentrations. Future studies are needed to establish whether other therapies that attenuate or prevent the effects of free hemoglobin result in more effective inhibition of lipid peroxidation in patients undergoing cardiopulmonary bypass.

Attempts to engineer a heart valve substitute have been performed over the last two decades with significant progress achieved in cell biology, biomaterial composition, and biomechanical stimulation. Application of tissueengineering techniques has become clinically relevant in urology, orthopedics, plastic surgery, and otolaryngology, treating defined pathologic entities which improve patient's quality of life and clinical practice [1]. From an epidemiologic standpoint, clinical relevance of tissue-engineered valves could affect millions of patients annually and alter the treatment algorithm for patients with both acquired and congenital valvar disease [2]. This manuscript offers insight into future biomaterials development utilizing techniques and advancements individually investigated. Combining the optimal mechanical properties achieved with electrospinning with biologic properties that support endothelial cell to mesenchymal cell transformation, a directed, possibly programmed, construct is plausible and the forefront of biomaterial design. Tissue-engineered constructs have a formidable task to meet and surpass current valve technology. While many cite the need for anticoagulation, the risk of calcification, limited durability, and the lack of growth potential as limitations, industry has made significant progress in mitigating these barriers. The stented bioprosthesis is the most utilized valve in clinical practice and has a low risk of thrombosis and thromboembolism. In most positions, the American Heart Association recommends an antiplatelet agent for anticoagulation, most often in the form of aspirin [3]. Anticalcification agents are proprietary for each valve and have improved with each generation of production. While data are being accrued, current shortand long-term follow-ups using both pericardial and porcine tissue valves show improved rates of calcification. Bioprosthetic valve durability has improved with each generation of valve design. Recent studies have shown maintenance of hemodynamics and bioprosthetic function up to 20 years in older patient cohorts [4]. The possibility of tissue-engineered heart valve growth with patient maturation could dramatically impact patient care. Valve companies have directed design and development effort to create catheter delivery systems with implantation in the pulmonary and aortic positions in the early stages of becoming accepted practice [5, 6]. By creating a stented valve that is expanded to conform to multiple defined size ranges, industry has created the first adjustable implant. As initial implants evaluate technique and efficacy, future investigation will include continued stent dilation and valve expansion as would be required for developing stenosis in the setting of somatic growth. Additionally, the less invasive techniques will impact reoperative open valve surgery. Clinical trials are being designed using catheter-inserted valves to replace previously placed valves in both the aortic and pulmonary positions (valve-in-a-valve concept) [7]. Current industry standards are elevating the benchmark required for clinical application of tissue-engineered heart valves as we continue to understand biologic principles This article is a commentary on the following article: 10.1007/s12265011-9300-4.

We describe a new method of selective regional perfusion during arch reconstruction in the Norwood procedure. The strategy involves direct sequential perfusion of the coronary and splanchnic circulations coupled with continuous cerebral perfusion, while repairing the arch in a distal to proximal fashion. This technique provides the potential for decreased coronary and splanchnic ischemic times, which in combination with continuous selective cerebral perfusion may further allow for warmer operating temperatures and decreased overall bypass times.

As a result of improved treatment of congenital heart disease (CHD) over the last half century, the number of patients reaching adulthood continues to grow. With increased success a challenging group of adults with unique anatomy and physiology, in addition to the usual effects of aging, has been created. All of these patients present unique and fascinating challenges, and their best care requires bridging pediatric and adult medical and surgical care. This review is a discussion of some of the more common surgical issues that arise in this evolving group of patients.

Purposes: We investigated whether circulating endothelial progenitor cells (EPCs) can be used as a cell source for the creation of a tissue-engineered heart valve (TEHV). Methods: Trileaflet valved conduits were fabricated using nonwoven polyglycolic acid/poly-4-hydroxybutyrate polymer. Ovine peripheral blood EPCs were dynamically seeded onto a valved conduit and incubated for 7, 14, and 21 days. Results: Before seeding, EPCs were shown to express CD31+, eNOS+, and VE-Cadherin+ but not α-smooth muscle actin. Histological analysis demonstrated relatively homogenous cellular ingrowth throughout the valved conduit. TEHV constructs revealed the presence of endothelial cell (EC) markers and α-smooth muscle actin+ cells comparable with native valves. Protein levels were comparable with native valves and exceeded those in unseeded controls. EPC-TEHV demonstrated a temporal pattern of matrix metalloproteinases-2/9 expression and tissue inhibitors of metalloproteinase activities comparable to that of native valves. Mechanical properties of EPC-TEHV demonstrated significantly greater stiffness than that of the unseeded scaffolds and native valves. Conclusions: Circulating EPC appears to have the potential to provide both interstitial and endothelial functions and could potentially serve as a single-cell source for construction of autologous heart valves.

Background Dogma suggests optimal myocardial protection in cardiac surgery after prior coronary artery bypass graft surgery (CABG) with patent left internal thoracic artery (LITA) pedicle graft requires clamping the graft. However, we hypothesized that leaving a patent LITA–left anterior descending (LAD) graft unclamped would not affect mortality from reoperative cardiac surgery. Methods Data were collected on reoperative cardiac surgery patients with prior LITA-LAD grafts from July 1995 through June 2006 at our institution. With the LITA unclamped, myocardial protection was obtained initially with antegrade cardioplegia followed by regular, retrograde cardioplegia boluses and systemic hypothermia. The Society of Thoracic Surgeons National Database definitions were employed. The primary outcome was perioperative mortality. Variables were evaluated for association with mortality by bivariate and multivariate analyses. Results In all, 206 reoperations were identified involving patients with a patent LITA-LAD graft. Of these, 118 (57%) did not have their LITA pedicle clamped compared with 88 (43%) who did. There were 15 nonsurvivors (7%): 8 of 188 (6.8%) in the unclamped group and 7 of 88 (8.0%) in the clamped group ( p = 0.750). Nonsurvivors had more renal failure ( p = 0.007), congestive heart failure ( p = 0.017), and longer perfusion times ( p = 0.010). When controlling for independently associated variables for mortality, namely, perfusion time (odds ratio 1.014 per minute; 95% confidence interval: 1.004 to 1.023; p = 0.004) and renal failure (odds ratio 4.146; 95% confidence interval: 1.280 to 13.427; p = 0.018), an unclamped LITA did not result in any increased mortality (odds ratio 1.370; 95% confidence interval: 0.448 to 4.191). Importantly, the process of dissecting out the LITA resulted in 7 graft injuries, 2 of which significantly altered the operation. Conclusions In cardiac surgery after CABG, leaving the LITA graft unclamped did not change mortality but may reduce the risk of patent graft injury, which may alter an operation.

Background— Valvular endothelial cells and circulating endothelial progenitor cells (EPCs) can undergo apparent phenotypic change from endothelial to mesenchymal cell type. Here we investigated whether EPCs can promote extracellular matrix formation in tissue engineering scaffolds in response to transforming growth factor (TGF)-β1. Method and Results— Characterized ovine peripheral blood EPCs were seeded onto poly (glycolic acid)/poly (4-hydroxybutyrate) scaffolds for 5 days. After seeding at 2×10 6 cells/cm 2 , scaffolds were incubated for 5 days in a roller bottle, with or without the addition of TGF-β1. After seeding at 15×10 6 cells/cm 2 , scaffolds were incubated for 10 days in a roller bottle with or without the addition of TGF-β1 for the first 5 days. Using immunofluorescence and Western blotting, we demonstrated that EPCs initially exhibit an endothelial phenotype (ie, CD31 + , von Willebrand factor + , and α–smooth muscle actin (SMA) − ) and can undergo a phenotypic change toward mesenchymal transformation (ie, CD31 + and α-SMA + ) in response to TGF-β1. Scanning electron microscopy and histology revealed enhanced tissue formation in EPC-TGF-β1 scaffolds. In both the 10- and 15-day experiments, EPC-TGF-β1 scaffolds exhibited a trend of increased DNA content compared with unstimulated EPC scaffolds. TGF-β1–mediated endothelial to mesenchymal transformation correlated with enhanced expression of laminin and fibronectin within scaffolds evidenced by Western blotting. Strong expression of tropoelastin was observed in response to TGF-β1 equal to that in the unstimulated EPC. In the 15-day experiments, TGF-β1–stimulated scaffolds revealed dramatically enhanced collagen production (types I and III) and incorporated more 5-bromodeoxyuridine and TUNEL staining compared with unstimulated controls. Conclusions— Stimulation of EPC-seeded tissue engineering scaffolds with TGF-β1 in vitro resulted in a more organized cellular architecture with glycoprotein, collagen, and elastin synthesis, and thus noninvasively isolated EPCs coupled with the pleiotropic actions of TGF-β1 could offer new strategies to guide tissue formation in engineered cardiac valves.

In previous studies we have shown that delayed capillary reperfusion after low flow bypass predicts neurologic injury. In this acute study, we hypothesized that low flow reduces endothelial nitric oxide synthase (eNOS) expression, which may lead to more profound inflammatory response and delayed capillary perfusion.Twelve piglets (13.2 +/- 0.7 kg) had a cranial window placed over the parietal cerebral cortex for direct examination of the microcirculation using intravital fluorescence microscopy. Animals were cooled to 15 degrees C or 34 degrees C on cardiopulmonary bypass (pH stat, hematocrit 30%, pump flow 100 mL/kg/minute) followed by 2 hours of low flow (50 mL/kg/minute) or very low flow (10 mL/kg/minute). Rhodamine staining was used to observe adherent and rolling leukocytes in postcapillary venules. The eNOS protein expression was determined by Western immunoblotting.High temperature and low flow rate correlated with significantly reduced eNOS expression (p0.01). Univariate comparisons based on Student t tests indicated that eNOS protein levels were lower at 34 degrees C than at 15 degrees C (0.7 +/- 0.6 vs 1.7 +/- 0.5, p0.01) and at 10 mL/kg per minute compared with 50 mL/kg per minute (0.8 +/- 0.7 vs 1.6 +/- 0.5, p = 0.03). Moreover, two-way analysis of variance revealed that temperature (F = 21.6, p0.001) and flow rate (F = 13.8, p = 0.005) were independent multivariate predictors of eNOS expression. During low flow bypass, eNOS was inversely correlated with numbers of adherent (p = 0.002) and rolling (p = 0.006) leukocytes, following an exponential decay curve closely.eNOS expression is reduced after very low flow bypass, particularly at a higher bypass temperature. This is associated with delayed capillary reperfusion. Reduced eNOS is also associated with increased white cell activation which may lead to greater neurologic injury.

Purpose Children after operative interventions for congenital heart disease (CHD-O) are frequently sensitized to HLA types from exposure to blood transfusions and cadaver tissue used for reconstructions. However, these anti-HLA antibody levels may fall with increasing time from surgery. It is possible that some CHD-O with a negative pre-transplant (Tx) PRA have been sensitized but are relatively quiescent at the time it is drawn. We hypothesized that a negative pre-Tx PRA might be falsely reassuring and that this group might be at increased risk for an early and marked rise in HLA antibodies with antigen re-exposure at implantation compared to children with cardiomyopathy (CM) or congenital heart disease with no prior cardiac surgery (CHD-N), both less likely to have had prior non-self exposure. Methods and Materials A retrospective chart review was done for all children undergoing heart Tx at our center to identify those with at least 6 mn post-Tx follow-up and at least 1 post-Tx PRA. Results The 123 children meeting criteria were divided into groups based on pre-Tx diagnosis: CM (N=50; AgeTx=5.2 y; FU=6.8y), CHD-N (N=21; AgeTx=0.28y; FU=11.8y) and CHD-O (N=52; AgeTx=6.6y; FU=7.3y). As age at Tx was much lower in the CHD-N group, subsequent analysis compared only CM and CHD-O which did not differ significantly for AgeTx or FU. A positive pre-Tx PRA (>10%) was present in 3.6% (CM) vs. 29% (CHD-O). If the pre-Tx PRA was negative, a positive post-Tx PRA was observed in 22% (CM) vs. 17% (CHD-O) (NS); and the median time post-Tx to positive PRA was 3.3 y; range 0.19-19 y (CM) vs. 2.2 y; range 0.019-12 y (CHD-O) (NS, p=0.40). Regardless of the pre-Tx PRA, donor specific antibody was seen in 18% (CM) and 19% (CHD-O) (NS) following Tx. Conclusions As long as the pre-Tx PRA is negative, prior congenital heart surgery does not appear to increase the likelihood of a positive post-Tx PRA or lead to an earlier appearance of positive PRA. Although some CHD-O with negative pre-Tx PRA develop anti-HLA antibody early post-Tx, it occurred no more often than in those transplanted for CM.

Purpose Acceptance and management of pediatric heart transplant (Tx) candidates with high pre-Tx PRA remains center dependent, largely due to lack of medium and longterm followup on outcomes. Some centers proceed only with a negative crossmatch, essentially guaranteeing no suitable donor in the worst cases. Other centers proceed across a positive crossmatch, feeling mortality is more likely waiting for a suitable donor, but with uncertain outcomes. We review outcomes after pediatric heart Tx with positive pre-Tx PRA (>10%) at a center that has not used prospective crossmatch, and more recently has chosen to transplant across a positive virtual crossmatch for those with markedly elevated PRA. Methods and Materials This is a retrospective chart review of all children undergoing heart transplantation at our center. Results We identified 19 recipients with pre-Tx PRA >10%: 11 class I, 2 class II, and 6 both class I and II. PRA class I mean was 43% (range 0-100) and class II mean was 27% (0-100). 11 of 18 tested had a positive retrospective crossmatch; 1 had no crossmatch. Only the 2 most recent recipients had specific intra-operative therapy to reduce antibody. Anti-thymocyte antibody induction is used. Post-Tx medications are often modified for better B cell coverage in this group. There were 5 deaths: rejection 2.3 y; rejection 3.2 y; PTLD 3.4 y; infection 7.0 y; and suicide 10.4 y. Both rejection deaths were linked to noncompliance. None of the high PRA recipients had documented coronary vasculopathy. Actuarial survival was 100% at 1 y; 79% at 5 y; 69% at 10y. 7 of 19 had rejection: 3 cellular, 2 AMR and 2 diagnosed clinically without biopsy. Time to first rejection was 1 y in 3. 3 recipients had >1 rejection episode. Positive crossmatch did not predict those likely to have rejection or death from rejection. Conclusions Reasonable outcomes in pediatric heart Tx recipients with high PRA, with or without a positive crossmatch, support offering Tx across a positive virtual crossmatch for those unlikely to otherwise undergo Tx.