Journal of Heart and Lung Transplantation最新文献

Background: Potential lung transplantation (LTx) recipients are assigned a donor sequence number (DSN) based on their position on the match list. Since a higher DSN offer has already been declined for other recipients, some providers may assume that a high DSN connotates poorer allograft quality. This study evaluated the association between DSN and outcomes, the correlation between transplant program case volume and the utilization of higher DSN lungs, and whether LTx outcomes differ between lower- and higher-volume programs.

Methods: Using the Scientific Registry of Transplant Recipients database, LTx cases from 2015-2021 were retrospectively reviewed. Recipients were categorized into low (<20), medium (21-50), high (51-100), and very high (>100) DSN groups. The primary outcome was LTx survival. For cases involving high or very high DSN donors, a subgroup analysis compared survival among programs with annual transplant volumes in the bottom, middle 2, and top quartiles.

Results: Median survival was similar among the low (6.9 years), medium (6.1), high (5.9), and very high DSN (6.5) groups (log-rank p = 0.09). Higher DSN donors were more commonly accepted by higher-volume LTx centers. However, the annual case volume of the transplanting institution did not impact survival when high (log-rank p = 0.16) or very high DSN (log-rank p = 0.36) donors were used.

Conclusions: Higher DSN should not be considered an independent marker of low allograft quality. Additionally, lower-volume centers achieved similar post-transplant outcomes as higher-volume centers for recipients receiving higher DSN lungs. These findings underscore that surgeons must judge each donor offer independent of other programs' assessments.

Background: Understanding donor factors associated with successful lung transplantation (LTx) following donation after circulatory death (DCD) is important in optimizing donor management. In this study, we examined critical care and ventilatory factors associated with DCD LTx and allograft survival using a unique detailed donor management database.

Methods: The Donor Management Goals national registry was queried for DCD donors between January 2016 and July 2023. The primary outcomes were DCD lung utilization and allograft survival. Multivariable modeling was used to assess factors associated with DCD LTx and allograft survival.

Results: A total of 3,394 donors met inclusion criteria and were included. Transplantation occurred in 202 (6.0%) cases with 85.6% 1-year survival. DCD LTx was more likely to occur following cerebrovascular accidents compared to anoxia and from donors who achieved a targeted PaO₂/FiO₂ (P/F) ratio at the time of organ allocation. Donor factors associated with decreased likelihood of LTx included increasing age, increasing INR, height greater than 168 cm, increasing hematocrit, and higher positive end-expiratory pressure (PEEP) at the time of organ allocation. Donor treatment with steroids and controlled mandatory ventilation, were associated with increased likelihood of graft failure at one year.

Conclusions: Successful DCD LTx associates with potentially modifiable donor parameters, including targeted P/F ratio, PEEP, INR, and hematocrit. Additionally, careful consideration of steroid use and ventilator settings may be important for improving long-term graft function. These modifiable factors may inform strategies to increase DCD LTx and improve survival.

Background: Surveillance bronchoscopies with bronchoalveolar lavage (BAL) and transbronchial biopsies (TBB) are primarily used to detect acute cellular rejection (ACR) or infection in lung transplant (LTx) recipients. We previously identified a BAL protein signature associated with chronic lung allograft dysfunction (CLAD) or death/retransplant in patients with stable minimal (grade A1) ACR. This present study aimed to determine whether similar BAL biomarkers predict outcomes in stable patients when ACR grade is undetermined.

Methods: The cohort included all adult, first bilateral LTx performed 2010-2017. Clinical status was categorized as unstable or stable based on the presence or absence of a ≥ 10% drop in FEV1. Clinically-stable patients with grade AX TBB (inadequate biopsies) during the first year post-transplant, not preceded by ACR (grade A≥1 or B≥1), were included. IL6, S100A8, IL10, TNF-receptor-1, IL1α, pentraxin3, and CXCL10 were measured in the BAL using a multiplex bead assay. Associations with subsequent CLAD or death/retransplant were assessed using multivariable Cox proportional hazards models, adjusted for relevant clinical covariates.

Results: Among 107 patients with stable AX biopsies at a median of 188 days post-transplant, the median times from biopsy to CLAD and death/retransplant were 972 and 1410 days, respectively. CXCL10 was significantly associated with CLAD, while IL6, S100A8, pentraxin3, TNF-receptor-1, and IL10 were associated with death/retransplant (p < 0.05 for all).

Conclusion: A focused BAL protein signature in stable patients with ungradable TBB early post-transplant may predict worse outcomes. Such select BAL biomarkers may identify patients who require more aggressive management strategies or closer monitoring.

Background: Primary graft dysfunction (PGD) remains the leading cause of 30-day mortality post-heart transplantation (HTx). HTx recipients experiencing severe PGD have been found to have high levels of circulating proteins associated with PGD occurrence and post-HTx survival. Whether treating these patients with therapeutic plasma exchange (TPE) can attenuate ongoing immunological and inflammatory processes and improve post-transplant outcomes has not been well-investigated. Therefore, we aim to examine the impact of treatment with TPE on 30-day and 1-year clinical outcomes of patients experiencing severe PGD post-HTx.

Methods: Between 2010 and 2022, we included 42 HTx patients who developed severe PGD. All included patients were placed on veno-arterial extracorporeal membrane oxygenation. We divided these patients into those who received TPE and those who did not (by physician choice). Endpoints included 30-day and 1-year survival, as well as 1-year-freedom from Any-treated rejection (ATR), acute cellular rejection (ACR), antibody-mediated rejection (AMR), biopsy negative rejection (BNR), cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), and freedom from left ventricular dysfunction (LVD) at 1-year post-HTx.

Results: Compared to patients who did not receive TPE, those managed with TPE had increased survival rates at 30 days (78.1% vs. 40%, p = 0.007) and at 1-year post-HTx (56.25% vs. 30% p = 0.035). However, no statistically significant differences were recorded in other outcomes of interest, including 1-year freedom from CAV, ATR, ACR, AMR, BNR, NF-MACE, or LVD.

Conclusion: TPE may serve as a promising therapeutic approach in HTx recipients experiencing severe PGD.

Background: Lower airway enrichment with oral commensals has been previously associated with severe primary graft dysfunction (PGD) after lung transplantation (LT). We aimed to determine whether this dysbiotic signature is present across all PGD severity grades and whether it is associated with a distinct host inflammatory endotype.

Methods: Lower airway samples from 96 LT recipients were used to evaluate the lung allograft microbiota via 16S rRNA gene sequencing. Bronchoalveolar lavage (BAL) cytokine concentrations and cell differential percentages were compared across PGD grades. In a subset of samples, we evaluated the lower airway host transcriptome using RNA sequencing methods.

Results: Differential analyses demonstrated lower airway enrichment with supraglottic-predominant taxa (SPT) in moderate and severe PGD. Dirichlet multinomial mixtures modeling identified 2 distinct microbial clusters. A greater percentage of subjects with moderate-severe PGD than no PGD were identified within the dysbiotic cluster (C-SPT, 48% and 29%, respectively) though this did not reach statistical significance (p = 0.06). PGD severity associated with increased BAL neutrophil concentration (p = 0.03) and correlated with BAL concentrations of MCP-1/CCL2, IP-10/CXCL10, IL-10, and TNF-α (p < 0.05). Furthermore, signatures of dysbiosis correlated with neutrophils, MCP-1/CCL-2, IL-10, and TNF-α (p < 0.05). C-SPT exhibited differential expression of TNF, SERPINE1, MPO, and MMP1 genes and upregulation of MAPK pathways, host signling associated with neutrophilic inflammation.

Conclusions: Lower airway dysbiosis within the lung allograft is associated with a neutrophilic inflammatory endotype, an immune profile commonly recognized as the hallmark for PGD. These data highlight a putative role of lower airway microbial dysbiosis in the pathogenesis of this syndrome.

Background: Heart transplantation (HT) survival and waitlist times are established outcome metrics. Patient-centered HT outcomes are insufficiently characterized. This study evaluates the role of days alive and outside the hospital (DAOH) as a candidate patient-centered HT performance measure.

Methods: The study cohort included Medicare beneficiaries undergoing HT (July 2008-December 2017). The percent of days outside of hospital (%DOH) 6 months before (%DOH-BF) and percent of days alive outside of hospital 12 months after HT (%DAOH-AF) were evaluated along with adverse events (AEs, early: ≤3 months; late: 4-12 months). Patients were stratified by patient %DAOH-AF terciles. Risk-adjusted %DAOH was evaluated across hospitals.

Results: A total of 5,104 beneficiaries underwent HT across 108 hospitals. Median [interquartile range (IQR)] age was 62 [53-67] years, 23.9% were female, and 21.4% were African-American. The overall median %DOAH-AF was 92.9% [83.8%, 95.9%], varying by tercile: low 71.8% [4.9%, 83.6%], intermediate 92.9% [91%, 94%]; high 96.4% [95.9%, 97.3%]. The lowest (vs highest) tercile %DAOH-AF had a lower median %DOH-BF (88% [73%-97%] vs 92% [81%-98%]) and longer post-HT inpatient stay (54 [36-81] vs 13 [10-15] days). After HT, the lowest versus highest tercile had greater AEs burden in the early (allograft failure [16.1% vs 1.6%], stroke [12.1% vs 2.3%]) and late (stroke [5.1% vs 1.9%], sternal wound infection [5.0% vs 0.8%]) phases post-HT. The mean hospital %DAOH_adj was 80.5% (min:max 57.7%-96.7%).

Conclusions: Post-HT %DAOH varies across beneficiaries and hospitals and is associated with AEs. Further research is warranted to assess the role and validity of %DAOH as an HT quality metric.

Background: Apixaban is increasingly used instead of vitamin K antagonists (VKAs) for long-term anticoagulation during HeartMate 3 (HM3) support. However, data on its pharmacokinetics in this context is lacking. We present real-world data on apixaban levels and outcomes in adult and pediatric HM3 patients, and evaluate our dosing strategy based on plasma sampling.

Methods: Since June-2023, all new HM3 recipients were initiated on apixaban. Additionally, hospitalized adult HM3 patients were transitioned from VKA to apixaban. Trough apixaban levels were measured in all patients, and dose adjustment was considered to exceed 50ng/ml.

Results: This retrospective study includes 34 HM3 patients, 4 pediatric (all primary use) and 30 adult patients (16 primary use). In primary use, apixaban was started at median of 14 (interquartile range [IQR]: 11-16, pediatric) and 11 (IQR: 6-13, adult) days postoperatively. No major coagulopathic events occurred during an overall follow-up of 3,191 patient-days. Six minor bleeding events occurred (0.69 events per patient-year), mostly (67%) during dual therapy with aspirin. Fourteen patients had dose adjustment; median trough and peak levels on final dosage were 73 (IQR: 50-92) and 179 (IQR: 133-242) ng/ml in the pediatric group and 109 (IQR: 83-144) and 176 (IQR: 134-228) ng/ml in the adult cohort, respectively. Inter- and intraindividual variation in apixaban peak levels was considerable, while trough levels showed less variability.

Conclusions: With a dosing strategy to target trough apixaban levels of >50ng/ml, there were no thrombotic events during a follow-up of 3,191 patient-days (of which 820 patient-days in children). We observed no major, and only few non-major bleeds, mainly in patients concomitantly taking aspirin.