The cost of lung transplantation in the United States: How high is too high?

Objectives: To identify patient and process factors that contribute to the high cost of lung transplantation (LTx) in the perioperative period, which may allow transplant centers to evaluate situations in which transplantation is most cost-effective to inform judicious resource allocation, avoid futile care, and reduce costs. Methods: The MarketScan Research databases were used to identify 582 privately insured patients undergoing single or bilateral LTx between 2013 and 2019. The patients were subdivided into groups by disease etiology using the United Network of Organ Sharing classification system. Multivariable generalized linear models using a gamma distribution with a log link were fit to examine the associations between the etiology of lung disease and costs during the index admission, 3 months before admission, and 3 months after discharge. Results: Our results indicate that the index admission contributed the most to the total transplantation costs compared to the 3 months before admission and after discharge. The regression-adjusted mean index hospitalization cost was 35% higher for patients with pulmonary vascular disease compared to those with obstructive lung disease ($527,156 vs $389,055). The use of extracorporeal membrane oxygenation, mechanical ventilation, and surgical complications in the post-transplantation period were associated with higher costs during the index admission. Surprisingly, age ≥55 was associated with lower costs during the index admission. Conclusions: This analysis identifies pivotal factors influencing the high cost of LTx, emphasizing the significant impact of the index admission, particularly for patients with pulmonary vascular disease. These insights offer transplant centers an opportunity to enhance cost-effectiveness through judicious resource allocation and service bundling, ultimately reducing overall transplantation costs.

Days alive and out of hospital for children born with single-ventricle heart disease.

BACKGROUND: This study describes the illness burden in the first year of life for children with single-ventricle heart disease, using the metric of days alive and out of hospital to characterize morbidity and mortality. METHODS: This is a retrospective single-centre study of single-ventricle patients born between 2005 and 2021 who had their initial operation performed at our institution. Patient demographics, anatomical details, and hospitalizations were extracted from our institutional single-ventricle database. Days alive and out of hospital were calculated by subtracting the number of days hospitalized from number of days alive during the first year of life. A multivariable linear regression with stepwise variable selection was used to determine independent risk factors associated with fewer days alive and out of hospital. RESULTS: In total, 437 patients were included. Overall median number of days alive and out of hospital in the first year of life for single-ventricle patients was 278 days (interquartile range 157-319 days). In a multivariable analysis, low birth weight (<2.5kg) (b = -37.55, p = 0.01), presence of a dominant right ventricle (b = -31.05, p = 0.01), moderate-severe dominant atrioventricular valve regurgitation at birth (b = -37.65, p < 0.05), index hybrid Norwood operation (b = -138.73, p < 0.01), or index heart transplant (b = -158.41, p < 0.01) were all independently associated with fewer days alive and out of hospital. CONCLUSIONS: Children with single-ventricle heart defects have significant illness burden in the first year of life. Identifying risk factors associated with fewer days alive and out of hospital may aid in counselling families regarding expectations and patient prognosis.

Gene delivery followed by ex vivo lung perfusion using an adeno-associated viral vector in a rodent lung transplant model.

OBJECTIVE: Ex vivo lung perfusion has emerged as a platform for organ preservation, evaluation, and restoration. Gene delivery using a clinically relevant adeno-associated vector during ex vivo lung perfusion may be useful in optimizing donor allografts while the graft is maintained physiologically active. We evaluated the feasibility of adeno-associated vector-mediated gene delivery during ex vivo lung perfusion in a rat transplant model. Additionally, we assessed off-target effects and explored different routes of delivery. METHODS: Rat heart-lung blocks were procured and underwent 1-hour ex vivo lung perfusion. Before ex vivo lung perfusion, 4e11 viral genome luciferase encoding adeno-associated vector 9 was administered via the left bronchus (Br group, n = 4), via the left pulmonary artery (PA group, n = 3), or directly into the circuit (Circuit group, n = 3). Donor lungs in the Control group (n = 3) underwent ex vivo lung perfusion without adeno-associated vector 9. Only the left lung was transplanted. Animals underwent bioluminescence imaging weekly before being killed at 2 weeks. Tissues were collected for luciferase activity measurement. RESULTS: All recipients tolerated the transplant well. At 2 weeks post-transplant, luciferase activity in the transplanted lung was significantly higher among animals in the Br group compared with the other 3 groups (Br: 1.1 × 106 RLU/g, PA: 8.3 × 104 RLU/g, Circuit: 3.8 × 103 RLU/g, Control: 2.5 × 103 RLU/g, P = .0003). No off-target transgene expression was observed. CONCLUSIONS: In this work, we demonstrate that a clinically relevant adeno-associated vector 9 vector mediates gene transduction during ex vivo lung perfusion in rat lung grafts when administered via the airway and potentially the pulmonary artery. Our preliminary results suggest a higher transduction efficiency when adeno-associated vector 9 was delivered via the airway, and delivery during ex vivo lung perfusion reduces off-target effects after graft implant.

Impact of simultaneous heart procurement on outcomes of donation after circulatory death lung transplantation.

Donation after circulatory death (DCD) heart procurement is done using either direct procurement (DP) or thoracoabdominal normothermic machine perfusion (TA-NRP). Both approaches could impact lung transplant outcomes with combined heart and lung procurements from the same donor. The impact of such practice on DCD lung transplant remains unstudied. We performed a retrospective analysis using the United Network for Organ Sharing (UNOS) dataset, identifying DCD lung transplants where the donor also donated the heart (cardia lung donor [CD]). A cohort of noncardiac DCD lung donors (noncardiac lung donor [NCD]) from the same era, matched for donor and recipient characteristics, was used as a comparison group. Both immediate and long-term outcomes were examined. A subanalysis was performed comparing the distinct impact of DP or TA-NRP on DCD lung transplant outcomes. Overall graft survival did not significantly differ between CD and NCD. However, recipients in the CD group trended toward a lower P/F ratio at 72 hours (CD vs NCD: 284 vs 3190; P = .054). In the subanalysis, we identified 40 DP donors and 22 TA-NRP donors. We found the both cohorts had lower P/F ratio at 72 hours than the NCD control (P = .04). Overall, 1-year graft survival was equivalent among the TA-NRP, DP, and NCD cohorts.