Journal of Heart and Lung Transplantation最新文献

Background: There are no specific criteria for listing and prioritizing lung transplantation (LTx) candidates based on the severity of right ventricular (RV) dysfunction. We evaluated the prognostic value of cardiac CT-derived RV ejection fraction (RVEF) in LTx candidates.

Methods: This retrospective study included patients who were listed for LTx and underwent cardiac computed tomography (CT) between September 2019 and December 2023. Patients were categorized into three groups based on CT-derived RVEF and survival analyses were performed among these groups: normal RVEF (≥ 45%), mild-to-moderate RV dysfunction (25%-45%), and severe RV dysfunction (< 25%).

Results: In the 203 patients (median age, 61 years [interquartile range [IQR], 54-64]), the most common indication for LTx was interstitial lung disease (79.3%). Patients were followed for a median duration of 297 days (IQR, 140-632), and the one-year survival rates were 85.2% for those with normal RV, 69.3% for those with mild-to-moderate RV dysfunction, and 55.6% for those with severe RV dysfunction (p < 0.001). Severe RV dysfunction (hazard ratio [HR] 6.72, p = 0.020), age (HR 1.1, p = 0.010), and 6-minute walking distance (HR 0.62, p = 0.010) were associated with an increased risk of one-year mortality.

Conclusions: Severe RV dysfunction identified on cardiac CT was a significant prognostic factor for one-year mortality in LTx candidates. Patients with severe RV dysfunction should be prioritized for LTx and classified as urgent due to their elevated short-term mortality risk. Cardiac CT may provide valuable prognostic information during the pre-transplant evaluation process.

Background: Autoantibodies and de novo donor HLA-specific antibodies (dnDSA) may contribute to chronic lung allograft dysfunction (CLAD). However, the breadth of reactivities against self-antigens and their association with CLAD has been underexamined. In a single-centre study, we screened lung transplant (LTx) recipients for novel autoantibodies at transplant and 6 months post-LTx, assessed dnDSA exposure, and tested their relationship with CLAD-free survival.

Methods: Serum samples were collected from 89 crossmatch-negative bilateral lung transplant recipients at the time of LTx and 6 months post-LTx, prior to a CLAD diagnosis, for autoantibody screening using a custom antigen microarray optimized for IgM and IgG detection.

Results: Patients who developed CLAD by 5 years post-LTx demonstrated a decrease in average IgG reactivity, but no decrease in IgM reactivity when measured at 6 months post-LTx. IgG anti-tropoelastin, SP-D, and thyroglobulin autoantibodies were significantly elevated 6 months post-LTx in patients who developed CLAD by 5 years, compared to those who remained CLAD-free at 5 years. In contrast, patients who remained CLAD-free at 5 years had elevated levels of IgG anti-CENP-B at both timepoints and PM/SCL100 at 6 months post-LTx, suggesting these may confer protection. Exposure to autoantibodies against lung-enriched targets, as opposed to ubiquitous antigens, and dnDSA conferred increased CLAD risk.

Conclusions: We have identified novel autoantibodies associated with CLAD-free survival. Our results bolster the independent relationship between autoantibodies and CLAD. We also identified autoantibody signatures that are associated with a marked increase in CLAD risk. Exposure to lung-enriched targets and dnDSA may have a reciprocal amplifying effect that lies on a tissue-specific mechanistic pathway leading to CLAD.

Background: The lack of effective drugs for treating ischemia-reperfusion injury (IRI) in lung transplants (LTx) remains an issue. Traditional Chinese medicine (TCM) ingredients are promising but poorly studied in LTx. This study aimed to identify potential ingredients and elucidate their mechanisms.

Methods: Ten TCM ingredients, including (-)-epigallocatechin-3-gallate, quercetin, wogonin, triptolide, berberine, fisetin, coumestrol, luteolin, nobiletin, and baicalein, were identified as promising candidates using a network pharmacology approach. All the candidates were tested for their ability to improve clamp-induced IRI. Multiple-dose validation was conducted in LTx models, with a focus on baicalein. The pharmacological efficacy of baicalin was verified in an ex-vivo rat lung perfusion model.

Results: All ten TCM ingredients improved clamp-induced IRI. Multiple-dose validation confirmed that baicalein mitigated IRI-induced graft damage and dysfunction. Baicalein reduced the elevated levels of advanced glycation endproducts (AGEs) and their downstream pathogenic effects induced by IRI. Exogenous AGEs counteracted the therapeutic effect of baicalein.

Conclusions: Baicalein inhibited AGE formation by modulating glucose oxidation rather than polyol metabolism. This study provides a laboratory foundation for the use of TCM ingredients in the treatment of IRI in LTx.

Background: This study evaluates outcomes following donation after circulatory death (DCD) heart transplantation in recipients with a durable left ventricular assist device (LVAD).

Methods: The UNOS registry was queried to analyze adult recipients of isolated DCD heart transplantation between 1/1/2019-3/31/2023. The recipients were stratified by durable LVAD use as a bridge to transplantation. The primary outcome was 1-year post-transplant survival. Sub-group analyses were conducted to evaluate the effects of transplant status, device type, and donor type on 1-year survival.

Results: A total of 703 recipients were included, of which 219 (31.2%) recipients were bridged with a durable LVAD. The recipients of DCD hearts with durable LVADs had significantly lower 1-year post-transplant survival compared to those without durable LVADs (88.4% vs. 93.6%, p=0.017). Among the recipients bridged with durable LVADs, status 4 recipients had significantly improved 1-year survival compared to statuses 2 and 3 recipients, similar to those without durable LVADs. Furthermore, the recipients with HeartMate II and HeartMate 3 had improved survival compared to those with the HeartWare HVAD, similar to those without durable LVADs. Lastly, the DCD and DBD recipients with durable LVADs had comparable 1-year survival (88.4% vs. 89.0%, p=0.763).

Conclusions: Recipients of DCD hearts bridged to transplantation with a durable LVAD exhibit reduced early post-transplant survival compared to those without a durable LVAD. However, clinical acuity and device type significantly influence post-transplant outcomes in this vulnerable population. Despite this, candidates with a durable LVAD can safely undergo DCD heart transplantation, achieving early post-transplant survival comparable to those of DBD heart transplantation.

Background: Schistosomiasis associated pulmonary arterial hypertension (Sch-PAH) is a highly relevant form of pulmonary hypertension, particularly in developing countries. Compared with idiopathic pulmonary arterial hypertension (IPAH), Sch-PAH has a better prognosis, though without identified mechanisms that justify this clinical course. Right ventricular-arterial pulmonary (RV-PA) coupling, expressed by the relationship between right ventricular contractility and afterload, has been studied as a potential marker of cardiac response to pulmonary vascular disease. However, there are no studies evaluating RV-PA coupling in Sch-PAH.

Methods: Retrospective cohort including patients diagnosed with Sch-PAH or IPAH who underwent right heart catheterization (RHC) at our institution from 2013 to 2018. Clinical and hemodynamic characteristics were reviewed and, by means of the recorded and digitized RHC pressure curves, right ventricular maximum isovolumic pressure (Pmaxiso) was estimated through the single-beat method to calculate right ventricular elastance at the end systole (Ees). The RV-PA was expressed by the Ees and the pulmonary artery elastance (Ea) ratio.

Results: A total of 101 patients were included (33 with Sch-PAH and 68 with IPAH). Sch-PAH patients were older (55.5 ± 15.1 vs 42.7 ± 15.2; p <0.001) with no significant difference in terms of traditional hemodynamics; nevertheless, Sch-PAH patients had better survival (p=0.031). Patients with Sch-PAH showed higher RV-PA coupling (0.95±0,58 vs 0.67±0.41; p = 0.004), higher Ees (2.07±1.65 vs 1.33±0.91; p = 0.005) without any difference in Pmaxiso and Ea compared with IPAH. At univariate analysis, RV-PA coupling was associated with survival. The RV-PA coupling remained an independent prognostic marker in the multivariable analysis adjusted for the type of pulmonary arterial hypertension (p = 0.030; HR = 0.287; 95% CI, 0.093-0.883).

Conclusions: RV-PA coupling is better preserved in Sch-PAH patients and is significantly associated with survival, suggesting that the right ventricular response to the increased afterload in Sch-PAH might represent an important pathophysiological mechanism that could explain the better clinical course observed in this relevant form of PAH.

The maximal donor age for lung transplantation (LTx) remains controversial, despite favorable outcomes with donors ≥70 years. We report our experience with LTx from donors ≥80 years. Donor/recipient characteristics and short-term postoperative outcome were retrospectively analyzed across two centers between 2016 and 2023. Seventeen patients underwent single (n=2) or double (n=15) LTx from octo- or nonagenarian donors with a median age of 83 years (range 80-94). Most donors were non-smoking females with intracerebral bleeding. Last donor PaO₂/FiO₂ ratio was 440 mmHg. Three recipients developed PGD3 at 72h. Median ICU and hospital stay were 11 and 29 days, respectively. Five patients showed minimal (A1) ACR at one month post-LTx. Two patients developed CLAD. One- and three-year survival rates were 84% and 70%. Our case series indicates that LTx from well-selected octo- and nonagenarian donors is a valuable option to expand the donor pool.