ECMO Bridge to Lung Transplant in Children with Idiopathic Pulmonary Arterial Hypertension.

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.

Reality of DCD donor use in pediatric thoracic transplantation in the United States.

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.

Donation after circulatory death significantly reduces waitlist times while not changing post-heart transplant outcomes: A United Network for Organ Sharing Analysis.

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.

Lung Transplantation for Pulmonary Vascular Disease in Children: A United Network for Organ Sharing Analysis.

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.

Lung Transplantation for Pulmonary Vascular Disease in Children: A United Network for Organ Sharing Analysis.

Background: 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. Methods: The UNOS Registry was queried from 1989-2020 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. Results: 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 towards 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). Conclusions: 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.

Impact of Size Matching on Survival Post Heart Transplant in Infants: Estimated Total Cardiac Volume Ratio Outperforms Donor-Recipient Weight Ratio.

PURPOSE: Cardiac volume-based estimation offers an alternative to donor-recipient weight ratio (DRWR) in pediatric heart transplantation (HT), but has not been correlated to post-transplant outcomes We sought to determine whether estimated Total Cardiac Volume (eTCV) ratio is associated with HT survival in infants. METHODS: The UNOS database was used to identify infants (age:<1year) who received HT in 1987-2020. Donor and recipient eTCV were calculated from weight using previously published data. Patient cohort was divided according to the significant range of eTCV ratio; characteristics and survival were compared. RESULTS: 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 1.05-1.85 whereas no range for DRWR was predictive. 75.6% patients had an optimal TCV 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=2151) had DRWR ranging from 1.09-5; 34.3% had DRWR 2-3, and 5.0% DRWR>3. CONCLUSION: Currently, an upper DRWR limit has not been established in infants. Therefore, determining the optimal eTCV range is important to identifying 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 includes DRWR values>2 that are traditionally not considered for candidate listing.

Exogenous nitric oxide delivery protects against cardiopulmonary bypass-associated acute kidney injury: Histologic and serologic evidence from an ovine model.

OBJECTIVE: Several human studies have associated nitric oxide administration via the cardiopulmonary bypass circuit with decreased incidence of cardiopulmonary bypass-associated acute kidney injury, but histopathologic and serologic evidence of nitric oxide efficacy for acute kidney injury attenuation are lacking. METHODS: By using a survival ovine model (72 hours), acute kidney injury was induced by implementing low-flow cardiopulmonary bypass for 2 hours, followed by full-flow cardiopulmonary bypass for 2 hours. The nitric oxide cohort (n = 6) received exogenous nitric oxide through the cardiopulmonary bypass circuit via the oxygenator, and the control group (n = 5) received no nitric oxide. Serial serologic biomarkers and renal histopathology were obtained. RESULTS: Baseline characteristics (age, weight) and intraoperative parameters (cardiopulmonary bypass time, urine output, heart rate, arterial pH, and lactate) were equivalent (P > .10) between groups. Postoperatively, urine output, heart rate, respiratory rate, and peripheral arterial saturation were equivalent (P > .10) between groups. Post-cardiopulmonary bypass creatinine elevations from baseline were significantly greater in the control group versus the nitric oxide group at 16, 24, and 48 hours (all P < .05). Histopathologic evidence of moderate/severe acute kidney injury (epithelial necrosis, tubular slough, cast formation, glomerular edema) occurred in 60% (3/5) of the control group versus 0% (0/6) of the nitric oxide group. Cortical tubular epithelial cilia lengthening (a sensitive sign of cellular injury) was significantly greater in the control group than in the nitric oxide group (P = .012). CONCLUSIONS: In a survival ovine cardiopulmonary bypass model, nitric oxide administered with cardiopulmonary bypass demonstrated serologic and histologic evidence of renal protection from acute kidney injury. These results provide insight into 1 potential mechanism for cardiopulmonary bypass-associated acute kidney injury and supports continued study of nitric oxide via cardiopulmonary bypass circuit for prevention of acute kidney injury.

Center volume effect on acute cellular rejection and outcomes in pediatric lung transplant recipients.

BACKGROUND: Acute cellular rejection (ACR) is common after lung transplant (LTx). We sought to determine if transplant center volume affected ACR-related outcomes in children after LTx. METHODS: The United Network for Organ Sharing (UNOS) Registry was queried for patients <18-years-of-age who underwent LTx 1987-2020. Cohorts were children who survived the first-year post transplant and were treated for ACR within that first year (ACR group) and those not treated for ACR (non-ACR). LTx center volume was defined as: high volume center (HVC) (>5LTxs/year), medium volume center (MVC) (>1≤5 LTxs/year), and low volume center (LVC) (≤1LTxs/year). RESULTS: 1320 patients were enrolled into the study; 269 (20.4%) did not experience ACR. The ACR cohort was older (median 14 [11-16] vs 13 [7-16] years, p < 0.001), female (65.3% vs 57.3%, p = 0.016), had cystic fibrosis (62.3% vs 45.5%, p < 0.001), and had a higher lung allocation score (37.3 [34.6-47.8] vs 35.8 [33-42.6], p = 0.029). The ACR cohort trended (p = 0.06) towards lower survival at 5-year (37% vs 47%) and 10-year (25% vs 34%) post-LTx. Among children at HVCs, ACR occurred in 17% of recipients (n = 98/574), compared to 18.5% (n = 73/395) at MVCs and 27% (n = 100/369) at LVCs. Children treated for ACR at HVCs had higher survival than LVCs at 5-years (52% vs 29%) and 10-years (36% vs 15%) (p < 0.001) but similar survival to MVCs at 5-years (52% vs 43%) and 10-years (36% vs 24%) (p = 0.081). No survival differences were detected in MVCs vs LVCs (p = 0.14). CONCLUSIONS: ACR treated within the first post-LTx year influence survival of children. ACR incidence was lowest at higher volume centers whereas post-ACR treatment survival outcomes were also superior.

Is the practice of using oversized organs for recipients with elevated pulmonary vascular resistance justified?

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.

Overly Selective Offer Acceptance is Associated With High Waitlist Mortality for the Most Ill Lung Transplant Candidates.

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.

Endocarditis in Bovine Vein Grafts in the Pulmonary Position Placed Surgically & Percutaneously.

Background: Infective endocarditis (IE) is one of the major complications following pulmonary valve replacement (PVR). This analysis hopes to evaluate the incidence, outcomes and possible risk factors of IE associated with trans-catheter and surgical placement of a bovine jugular vein (BJV) graft in the pulmonary position. Methods: In this single-center retrospective study, all records of trans-catheter and surgical PVR from 3/2010 to 12/2019 were reviewed. IE was defined as positive blood cultures, with vegetations seen on echocardiography or sudden increase in peak gradient across the valve or vegetations confirmed at time of valve replacement. Poor dental hygiene:1.dental procedures without S.B.E prophylaxis AND/OR 2.one or more dental cavities, caries, dental abscess. Results: 165 patients had PVR with BJV:107 trans-catheter and 63 surgical. 7%(12/170) of PVRs developed IE(catheter:n = 10, surgery:n = 2) at a median time from valve placement of 38 months. The incidence of IE in the catheter group:3-per-100patient-years and in surgical group:1-per-100patient-years. Multivariate cox regression showed that poor dental hygiene was significantly associated with IE [HR(95% CI):16.9(4.35-66.2)](p value <.001). Kaplan-Meier curves showed a significant difference in freedom from IE between patients with poor and appropriate dental hygiene (p value<.001). Conclusions: There is a 7% incidence of IE with the use of BJV grafts in the pulmonary position at mid-term follow-up. Though the rate in catheter placed BJV seems 3x higher than surgically placed ones, their cohorts are quite different making this comparison flawed. Poor dental hygiene is a strong predictor for post-operative IE and offers a significant opportunity for lowering the rate of infective endocarditis.

More Than 400 Uses of an Intestinal Submucosal Extracellular Matrix Patch in a Congenital Heart Program.

BACKGROUND: Repair of complex congenital heart disease frequently requires use of a patch as an anatomic substitute. The study's aim is to evaluate the use, effectiveness, and safety of using small intestine submucosal extracellular matrix (SIS-ECM) patches in a congenital cardiac surgery program. METHODS: This is a single-center, retrospective, cohort study of surgeries using SIS-ECM between 2012 and 2019. The SIS-ECM data were categorized by use and type (four-ply and two-ply). All reinterventions and complications were reviewed by an independent surgeon, a practicing congenital heart surgeon, and a pediatric cardiologist. RESULTS: In all, 408 SIS-ECM patches were used in 309 patients (188 male, 121 female; median age 8.5 months). Use of the patches consisted of 314 arterioplasties (77%), 22 venoplasties (5.4%), 63 intracardiac repairs (15.4%), and 9 valve repairs (2.2%). The most common use was for pulmonary artery repair (n = 181; 44.4%). Median follow-up time was 3.9 years (range, 3 days to 7.4 years). Ten patches (2.5%) required surgical reintervention (2 in the first 30 days and 5 in the first year) and 27 (6.6%) required percutaneous reinterventions (2 in the first 30 days and 22 in the first year). Between four-ply (n = 376) and two-ply (n = 32) SIS-ECM, the rate of surgical (2.1% [n = 8] vs 6.3% [n = 2], P = .18) or percutaneous reinterventions (6.4% [n = 24] vs 9.4% [n = 3], P = .46) was not different. There were no deaths related to the SIS-ECM patch or reports of calcification. CONCLUSIONS: The SIS-ECM is a viable patch option that can be used in various cardiac and vascular reconstructive surgeries with low risk of failure and calcification. Long-term, positive outcomes may be maximized by using consistent techniques and understanding the appropriate applications of the patch.

Paravalvular leak closure with real time transesophageal echocardiography and fluoroscopy fusion.

Transcatheter technology has been increasingly used for paravalvular leak closure. We report the use of "Fusion Technology" (EchoNaviagator, Phillips, Tustin, CA) that combines real-time 2 and 3 dimensional trans-esophageal echocardiography with fluoroscopy imaging to facilitate paravalvular leak closure. This could help to identify the exact site, size, depth and shape of the paravalvular leak for proper positioning of the occluder device, which may result in saving time and effort.