Journal of Heart and Lung Transplantation最新文献

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.

Aim: 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.

Rationale: Lower airway enrichment with oral commensals has been previously associated with grade 3 severe primary graft dysfunction (PGD) after lung transplantation (LT). We aimed to determine whether this dysbiotic signature is present across all PGD severity grades, including milder forms, and whether it is associated with a distinct host inflammatory endotype.

Methods: Lower airway samples from 96 LT recipients with varying degrees of PGD 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 both moderate and severe PGD. Dirichlet Multinomial Mixtures (DMM) modeling identified two distinct microbial clusters. A greater percentage of subjects with moderate-severe PGD were identified within the dysbiotic cluster (C-SPT) than within the no PGD group (48 and 29%, respectively) though this difference 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, microbial 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 (PAI-1), MPO, and MMP1 genes and upregulation of MAPK pathways, suggesting that dysbiosis regulates host signaling to promote 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 pathogenesis. This data highlights a putative role for 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) six 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 [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 (versus highest) tercile %DAOH-AF had a lower median %DOH-BF (88% [73%-97%] versus 92% [81%-98%]) and longer post-HT inpatient stay (54 [36-81] versus 13 [10-15] days). After HT, the lowest versus highest tercile had greater AEs burden in the early [allograft failure (16.1% versus 1.6%), stroke (12.1% versus 2.3%)], and late [stroke (5.1% versus 1.9%), sternal wound infection (5.0% versus 0.8%)] phases post-HT. 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 a 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 (IQR:11-16, pediatric) and 11 (IQR:6-13, adult) days postoperatively. No major coagulopathic events occurred during an overall follow-up of 3191 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 3191 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.