Faculty Bibliography

OBJECTIVE:Donation after circulatory death (DCD) lung transplantation has increased, but there is limited data in children. We sought to characterize the international experience of pediatric DCD lung transplant (LT) in comparison to donation after brain death (DBD) to address extreme donor organ shortages in children needing LT. METHODS:Using the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry, 1453 children (<18yo) LT recipients from January 2004 to June 2018 were identified: 34 (3%) were DCD and 1419 (97%) were DBD recipients. Post-transplant outcomes were compared between groups. Propensity score method was used to derive matched cohorts and were compared between groups. RESULTS:DCD and DBD recipients were of similar age, with cystic fibrosis being the most frequent indication for LT in both groups (64.5% vs. 57.5%, respectively). Kaplan-Meier analysis demonstrated similar survival between DCD and DBD cohorts, whereas propensity score-matched recipients also identified similar post-transplant survival in both groups (P=0.098). Secondary analysis found that DCD LT recipients had a longer post-transplant length of hospital stay (unmatched cohorts: 36.5d vs. 20d, p=0.022; matched cohort: 26d vs. 19d, p=0.016), and shorter time to acute cellular rejection (ACR) (unmatched cohorts: 248d vs. 560d, p=0.039; matched cohorts: 248d vs. 1650d,p=0.059). CONCLUSIONS:Due to DCD being a key contributor to the increasing number of lung transplants being performed worldwide, the results of this analysis support this organ donation approach in children requiring LT, which would increase access to donor organs. The identification of a potential shorter time to ACR needs further exploration as more DCD pediatric LTs are performed.

BACKGROUND:Stroke affects surgical decision making and outcomes of neonatal cardiac surgery (CHS). We sought to assess the burden of stroke in this population from a large multicenter database. METHODS:We analyzed neonates undergoing CHS with cardiopulmonary bypass from the Pediatric Health Information System database (2004-2022). The cohort was divided into the stroke group, which included preoperative/postoperative ischemic, hemorrhagic subtypes, and grade III to IV intraventricular hemorrhages, and compared in-hospital and follow-up outcomes to a nonstroke group. RESULTS:A perioperative stroke occurred in 800 of 14,228 neonates (5.6%). The stroke group was more likely to have hypoplastic left heart syndrome (HLHS; 30.5% vs 20.7%), born preterm (19.4% vs 11.7%), low birth weight (17.8% vs 11.9%), and require extracorporeal membrane oxygenation (ECMO; 48.8% vs 13.8%; all P < .001). Outcomes comparing stroke vs no stroke were mortality, 33.1% vs 8.9%; nonhome discharge, 12.5% vs 6.9%; length of stay, 41 vs 24 days; and hospitalization costs, $354,521 vs $180,489 (all, P < .05). Stroke increased the odds of mortality by 2-fold (odds ratio, 2.20; 95% CI, 1.75-2.77; P < .001) after adjusting for ECMO, prematurity among other significant factors. On follow-up, the stroke group had a higher incidence of hydrocephalus (9.5% vs 1.3%), cerebral palsy (6.2% vs 1.3%), and autism spectrum disorder (7.1% vs 3.5%), and survivors of the index admission had higher 1- and 5-year mortality (5.3% and 11.3% vs 3.3% and 5.9%, respectively; all P < .05). CONCLUSIONS:Neonatal CHS patients born prematurely, diagnosed with HLHS, or those requiring ECMO are disproportionately affected by stroke. The occurrence of stroke is marked by significantly higher mortality. Future research should seek to identify factors leading to stroke to increase rescue after stroke and for improvement of long-term outcomes.

Idiopathic pulmonary arterial hypertension (IPAH) represents an important clinical indication for lung transplant (LTx) in children. Recent trends show fewer children with IPAH are undergoing LTx nowadays compared to previous time periods, including those with most severe form of the disease. Using the UNOS Registry, we investigated if ECMO at the time of transplant impacts post-transplant survival in children with IPAH. A total of 74 LTx recipients while on ECMO at the time of transplant were identified (IPAH: N = 12). Children with IPAH who underwent LTx while on ECMO had shown comparable survival rates to those who were on ECMO for other conditions. This analysis provides encouraging results, supporting the potential expansion of LTx for this patient population. Given the low number of children undergoing LTx, we think there should be a consensus document to provide better guidance for referring and selecting the high-risk pediatric population with IPAH on ECMO for lung transplant.

BACKGROUND:Cardiac volume-based estimation offers an alternative to donor-recipient weight ratio (DRWR) in pediatric heart transplantation (HT) but has not been correlated to posttransplant outcomes. We sought to determine whether estimated total cardiac volume (eTCV) ratio is associated with HT survival in infants. METHODS:The United Network for Organ Sharing database was used to identify infants (aged <1 year) who received HT in 1987-2020. Donor and recipient eTCV were calculated from weight using previously published data. Patient cohort was divided acc ording to the significant range of eTCV ratio; characteristics and survival were compared. RESULTS:A total of 2845 infants were identified. Hazard ratio with cubic spline showed prognostic relationship of eTCV ratio and DRWR with the overall survival. The cut point method determined an optimal eTCV ratio range predictive of infant survival was 1.05 to 1.85, whereas no range for DRWR was predictive. Overall, 75.6% of patients had an optimal total cardiac volume ratio, while 18.1% were in the lower (LR) and 6.3% in the higher (HR) group. Kaplan-Meier analysis showed better survival for patients within the optimal vs LR (p = 0.0017) and a similar significantly better survival when compared to HR (p = 0.0053). The optimal eTCV ratio group (n = 2,151) had DRWR, ranging from 1.09 to 5; 34.3% had DRWR of 2% to 3%, and 5.0% had DRWR of >3. CONCLUSIONS:Currently, an upper DRWR limit has not been established in infants. Therefore, determining the optimal eTCV range is important to identify an upper limit that significantly predicts survival benefit. This finding suggests a potential increase in donor pool for infant recipients since over 40% of donors in the optimal eTCV range include DRWR values >2 that are traditionally not considered for candidate listing.

BACKGROUND:Recently, several centers in the United States have begun performing donation after circulatory death (DCD) heart transplants (HTs) in adults. We sought to characterize the recent use of DCD HT, waitlist time, and outcomes compared to donation after brain death (DBD). METHODS:Using the United Network for Organ Sharing database, 10,402 adult (aged >18 years) HT recipients from January 2019 to June 2022 were identified: 425 (4%) were DCD and 9,977 (96%) were DBD recipients. Posttransplant outcomes in matched and unmatched cohorts and waitlist times were compared between groups. RESULTS:DCD and DBD recipients had similar age (57 years for both, p = 0.791). DCD recipients were more likely White (67% vs 60%, p = 0.002), on left ventricular assist device (LVAD; 40% vs 32%, p < 0.001), and listed as status 4 to 6 (60% vs 24%, p < 0.001); however, less likely to require inotropes (22% vs 40%, p < 0.001) and preoperative extracorporeal membrane oxygenation (0.9% vs 6%, p < 0.001). DCD donors were younger (29 vs 32 years, p < 0.001) and had less renal dysfunction (15% vs 39%, p < 0.001), diabetes (1.9% vs 3.8%, p = 0.050), or hypertension (9.9% vs 16%, p = 0.001). In matched and unmatched cohorts, early survival was similar (p = 0.22). Adjusted waitlist time was shorter in DCD group (21 vs 31 days, p < 0.001) compared to DBD cohort and 5-fold shorter (DCD: 22 days vs DBD: 115 days, p < 0.001) for candidates in status 4 to 6, which was 60% of DCD cohort. CONCLUSIONS:The community is using DCD mostly for those recipients who are expected to have extended waitlist times (e.g., durable LVADs, status >4). DCD recipients had similar posttransplant early survival and shorter adjusted waitlist time compared to DBD group. Given this early success, efforts should be made to expand the donor pool using DCD, especially for traditionally disadvantaged recipients on the waitlist.

Pulmonary vascular disease (PVD) represents an important clinical indication for lung transplant (LTx) in infants, children, and adolescents. There is limited information on LTx outcomes in these patients. We explored LTx volumes and post-LTx survival in children with PVD compared to other diagnoses. The UNOS Registry was queried from 1989 to 2020 to identify first-time pediatric LTx recipients (< 18 yo). PVD was categorized as idiopathic pulmonary arterial hypertension (IPAH) and non-idiopathic arterial hypertension (non-IPAH) and compared to all other patients as other diagnoses. Univariate and multivariate regression models were performed. 984 pediatric LTx patients (593 before 2010 and 391 during/after 2010) were identified, of which 145 (14.7%) had PVD. There has been no significant change in annual rate of all LTxs over comparative eras. However, there has been a decrease in rate of LTxs for PVD patients. Children with PVD had similar survival to other LTx groups in the early era (p = 0.2) and the latter era (p = 0.9). Univariate Cox models, showed that LTx in patients with PVD was associated with a significantly less risk of mortality for children aged 6-11 years compared to younger and older cohorts (HR = 0.4 [0.17-0.98]; p = 0.045), whereas multivariate analysis showed a trend toward higher mortality in 11-17-year-olds (HR = 1.54 [0.97-2.45]; p = 0.06). For PVD patients, oxygen supplementation and ventilator support at LTx were associated with worse post-transplant survival (p = 0.029 and p = 0.01). There has been a decrease in LTx volume for pediatric patients with PVD in the modern era. Post-LTx outcomes for children with PVD are similar to those of other diagnoses in both eras, with children aged 6-11 years having the best survival. Given these findings, LTx should be considered for this patient population.

In the US, the first pediatric donation after circulatory death (DCD) thoracic transplant was done in 2004; however, ethical controversy led to minimal utilization of these donors. The present study was performed to characterize the current state of pediatric DCD heart and lung transplantation (HTx, LTx). Children (<18 year old) who underwent HTx or LTx using DCD donors from June 2004 to June 2022 were identified in the United Network for Organ Sharing registry. A total of 14 DCD recipients were identified: 7 (50%) HTx and 7 (50%) LTx. Donor and recipient demographics are described in Table 1. One and 5-year post-transplant survival were as follows: HTx recipients (64% for each) and LTx recipients (86%, 55%). Although often discussed, the national experience with DCD donors for pediatric HTx and LTx remains limited and not being practiced consistently by any pediatric program. Given the critical organ shortage, DCD use in the field of pediatric thoracic transplantation should be strongly considered.

The demand for organs for lung transplantation (LTx) continues to outweigh supply. However, nearly 75% of donor lungs are never transplanted. LTx offer acceptance practices and the effects on waitlist/post-transplant outcomes by candidate clinical acuity are understudied. UNOS was used to identify all LTx candidates, donors, and offers from 2005 to 2019. Candidates were grouped by Lung Allocation Score (LAS; applicable post-2005, ages ≥12 years): LAS<40, 40-60, 61-80, and >80. Offer acceptance patterns, waitlist death/decompensation, and post-transplant survival (PTS) were compared. "Acceptable organ offers" were those from donors whose organs were accepted for transplantation. Approximately 3 million offers to 34,531 candidates were reviewed. Median waitlist durations were: 9 days-(LAS>80), 17 days-(LAS 61-80), 42 days-(LAS 40-60), 125 days-(LAS<40) (P < 0.001 between all). Per waitlist-day, offer rates were: total offers - 0.8/day-(LAS>80), 0.7/day-(LAS 61-80), 0.6/day-(LAS 40-60), 0.4/day-(LAS<40); acceptable offers - 0.34/day-(LAS>80), 0.32/day-(LAS 61-80), 0.24/day-(LAS 40-60), 0.15/day-(LAS<40) (both P < 0.001 between all LAS). Among patients who experienced waitlist mortality/decompensation, ≥1 acceptable offer was declined in 92% (3939/4270) of patients - 78% for LAS >80, 88% for LAS 61-80, 93% for LAS 40-60, and 96% for LAS <40. Thirty-day waitlist mortality/decompensation rates were: 46%-(LAS>80), 24%-(LAS 61-80), 5%-(LAS 40-60), <1%-(LAS<40) (P < 0.001 between all). PTS was equivalent between patients for whom the first/second offer vs later offers were accepted (all LAS P > 0.4). The first offers that LTx candidates receive (including acceptable organs) are declined for nearly all candidates. Healthier candidates can afford offer selectivity but more ill patients (LAS>60) cannot, experiencing exceedingly high 30-day waitlist mortality.

OBJECTIVE:The purpose of this study was to assess post-transplantation outcomes in recipients with increased pulmonary vascular resistance (PVR) in relation to donor size. METHODS:The United Network for Organ Sharing database was used to identify patients ages 0 to 18 years at time of listing who underwent transplantation from 2010 to 2019 and for whom cardiac catheterization and donor-recipient weight ratio data were available. Patients were divided according to listing PVR into <3, 3 to 6, and >6 Wood units. Donor-recipient weight ratio was categorized as undersized (≤0.80), midsize (0.81-1.2), and oversized (>1.2). Subgroup analysis was done with an additional supersized group (>2.0). RESULTS:Fourteen hundred ninety-one patients met study criteria. Median age was 10 (interquartile range, 3-15) years and 45% were female. Four percent of heart transplantation cases used undersized, 45% used midsize, and 51% used oversized organs. More patients with PVR >6 were received an oversized organ transplant compared with patients with PVR <3; 59% (148/252) versus 48% (430/894); P = .003. There was no difference in survival among organ size groups regardless of PVR; this includes patients with PVR >6 at listing who received an oversized organ transplant versus an undersized (P = .359) or midsized (P = .956) organ. In subgroup analysis, even in patients who received a supersized organ transplant, there was no survival difference noted regardless of PVR. CONCLUSIONS:Despite a persistent practice pattern to transplant oversized organs in high-PVR patients, there remains no difference in post-transplantation survival among these patients and those who received smaller organ transplants. Therefore, transplants in patients with high PVR should not be delayed by waiting for larger donors.