Journal of Heart and Lung Transplantation最新文献

Background: This analysis examined the effects of the activin signaling inhibitor, sotatercept, in pulmonary arterial hypertension (PAH) subgroups stratified by baseline cardiac index (CI).

Methods: Pooled data from PULSAR (N = 106; NCT03496207) and STELLAR (N = 323; NCT04576988) were analyzed using 2 different CI thresholds, <2.0 and ≥2.0 liter/min/m² as well as <2.5 and ≥2.5 liter/min/m². Median changes from baseline at week 24 were evaluated using Hodges-Lehmann estimator and least squares (LS) means, with 95% confidence intervals and p-values (significance: p = 0.05). Categorial endpoints and time-to-clinical worsening were analyzed by Cochran-Mantel-Haenszel and Cox model respectively.

Results: Of 429 participants, 51 had CI <2.0 and 378 ≥2.0 liter/min/m², while 179 had CI <2.5 and 250 ≥2.5 liter/min/m². Sotatercept significantly improved median 6-minute walk distance (range: 33.9 to 63.7 m: p < 0.001), pulmonary vascular resistance (range: -202.8 to -395.4 dyn•s•cm^-5; p ≤ 0.002), and N-terminal pro-B-type natriuretic peptide (range: -317.3 to -1,041.2 pg/ml; p < 0.001) across subgroups. LS means showed reductions in pulmonary and right atrial pressures, decreased right ventricular size, and improved tricuspid annular plane systolic excursion/systolic pulmonary artery pressure. Sotatercept delayed time to first occurrence of death or a worsening event for CI ≥2.5 (hazard ratio [HR] 0.12; p < 0.001), ≥2.0 (HR 0.13; p < 0.001), and <2.5 (HR 0.21; p < 0.001) liter/min/m². Improvements were observed in WHO functional class (all p < 0.050) and ESC/ERS risk scores (all p < 0.001).

Conclusions: Sotatercept demonstrated consistent efficacy and safety across CI subgroups, supporting its use in PAH patients irrespective of baseline cardiac hemodynamics.

Patients 65 years of age or older represent the fastest-growing demographic group added to the U.S. heart transplant (HT) list. While post-HT outcomes appear acceptable, immortal time bias is introduced if adverse outcomes that occur while waiting for HT are not considered. Recent durable left ventricular assist device (dLVAD) technological innovations have engendered the question of whether this patient subgroup would achieve equivalent survival from a strategy of primary dLVAD implant as opposed to HT listing. We identified adults ≥65 years of age listed for HT between 2018 and 2021, excluding persons with dLVAD support and/or multiorgan listing. Among 1,176 patients, 2-year survival from HT listing was 78.4% ± 1.2%, similar to the 71% to 75% reported in The Society of Thoracic Surgeons (STS) Intermacs National Database for older adults. Linkage of the Scientific Registry of Transplant Recipients with STS Intermacs would enable comparative effectiveness analyses of surgical heart failure therapeutic strategies in high-risk patient cohorts.

Background: Device-related infection (DRI) remains a cause of morbidity and mortality following durable left ventricular assist device (dLVAD) implantation. We evaluated outcomes following pump exchange (PE) for DRI following dLVAD implantation.

Methods: Forty-nine patients underwent PE between 1/2007 and 12/2022 for major DRI. Outcomes included survival, incidence of subsequent DRI, and proportion of patients achieving success (freedom from DRI at 1-year following PE).

Results: Median age was 49 years. Median time from primary implant to DRI diagnosis and from diagnosis to PE was 26 and 4.1 months, respectively. Median time to DRI recurrence was 5.8 months with 76% of patients achieving success. Success was obtained in 23/24 (96%) of patients whose time to PE from DRI diagnosis was ≤4 months and 14/25 (56%) if time >4 months.

Conclusion: Most patients achieve success following PE for DRI. The risk of subsequent DRI and mortality remains high. Early (≤4 months) PE following DRI diagnosis increases the likelihood of success, while reducing the rate of subsequent DRI.

Background: Basiliximab induction immunosuppression is increasingly employed in lung transplant recipients despite limited prospective evidence to support its use in this population. We sought to determine the relationship between basiliximab induction and development of acute rejection, chronic lung allograft dysfunction, and other clinically relevant outcomes in a multicenter lung transplant cohort with variable induction practice patterns.

Methods: We applied propensity-based statistical methods to rigorous, prospectively collected longitudinal data from 768 newly transplanted adult lung recipients at 5 North American centers (368 who received basiliximab induction immunosuppression and 400 who received no induction immunosuppression). Treatment effects were estimated using outcome-specific propensity score regression models, weighted by the outcome-specific overlap weights, and stratified by center strata.

Results: Basiliximab induction immunosuppression was associated with a significant reduction in any grade acute rejection (HR 0.65, 95% CI 0.46-0.92; p=0.015), organizing pneumonia histology (HR 0.38, 95% CI 0.16-0.90; p=0.028), acute lung injury histology (HR 0.28, 95% CI 0.13-0.61; p=0.001), and development of class II donor specific antibodies (HR 0.51, 95% CI 0.27-0.95; p=0.034) within the first posttransplant year. However, there was no significant association between basiliximab and development of chronic lung allograft dysfunction, mortality, or graft loss. For select infections during the first posttransplant year, there was no evidence of a difference in risk between patients who did versus did not receive basiliximab.

Conclusions: Basiliximab induction immunosuppression is associated with a significant reduction in early posttransplant cellular and humoral immune events and lung injury histologies but not chronic lung allograft dysfunction or mortality.

There is a paucity of data reporting the positive and negative predictive values (PPV, NPV) of acute declines in lung function on chronic lung allograft dysfunction (CLAD). We sought to define the predictive ability of single or repeated forced expiratory volume in the first second (FEV₁) declines for at least 3 weeks on the development of CLAD or death by 1-year. We analyzed 340 subjects with at least 3 years of follow-up data from two lung transplant centers. A single ≥10% FEV₁ decline had a PPV of 35% and NPV of 63%, and a repeated ≥10% FEV₁ decline for at least 3 weeks had a PPV of 44% and NPV of 65%. Notably, the proportion of individuals with incipient CLAD at the time of a single or repeated ≥20% FEV1 decline was 50% and 71%, respectively. These estimates could inform the development of acute lung allograft dysfunction FEV₁ thresholds as enrollment criteria or surrogate outcome measures.

Background: The criteria for evaluating donations after circulatory death (DCD) heart allografts, particularly donor cardiopulmonary resuscitation (CPR) status, remains underexplored. This study evaluates the impact of donor CPR on post-transplant outcomes in DCD heart transplants.

Methods: The UNOS registry was queried to analyze adult recipients who underwent DCD heart transplantation between 1/1/2019 and 3/31/2023, with a 1-year follow-up period extending to 3/31/2024. Primary outcomes were 90-day and 1-year post-transplant survival. 1:1 propensity score-matching was performed. Restricted cubic spline was used to model duration of CPR and likelihood of 1-year post-transplant mortality. Sub-analysis was performed to evaluate the effects of CPR duration on donor heart utilization.

Results: A total of 683 DCD recipients were included, and 378 recipients (55.3%) received hearts from donors that underwent CPR. Recipients with donors who received CPR had similar 1-year (92.1% vs 90.7%) post-transplant survival compared to recipients with donors who did not receive CPR. The comparable post-transplant survival persisted in a propensity score-matched comparison. The spline model demonstrated that longer duration of CPR was not associated with lower odds of 1-year post-transplant survival compared to the reference of 15 minutes. In the sub-analysis, longer CPR duration was not significantly associated with reduced donor heart utilization.

Conclusions: Donors that received CPR requires consideration for DCD transplants since damage during cardiac arrest prior to withdrawal of life support may amplify warm ischemic injury during procurement. This study suggests that the use of DCD hearts that underwent CPR can expand the donor pool without compromising early post-transplant survival.

Objective: This study compares the incidence of severe Primary Graft Dysfunction (PGD) in a contemporaneous cohort of donors after circulatory death (DCD) and brain death (DBD) heart transplant recipients.

Method: The United Network for Organ Sharing database was queried for isolated adult heart transplant recipients from 9/2023 to 6/2024. Heart recipients were stratified based on the organ donation type (DCD vs DBD). DCD heart recipients were further categorized based on the procurement method: time between circulatory death to cross-clamp: ≤ 30 minutes (Direct Procurement and Preservation, DPP), >30 minutes (Normothermic Regional Perfusion, NRP). Outcomes of interest included: severe PGD (Left/Bi-Ventricular; LV/BiV) at 24 hours and Severe Graft Dysfunction at 72 hours (patients with severe PGD at 24 hours that remain on mechanical support at 72 hours).

Results: A total of 2590 adult heart transplant recipients were identified, of which 17.1% underwent DCD heart transplantation. DCD heart recipients were less likely to be on inotrope (36.7% vs 41.6%, p=0.046) and ECMO (4.1% vs 9.9%, p<0.001) prior to transplant than DBD heart recipients. DCD heart recipients were more likely than DBD heart recipients to develop severe PGD (LV/BiV) at 24 hours (9.5% vs 5.1%, p<0.001). The Severe Graft Dysfunction at 72 hours (2.3% vs 2.9%, p=0.67) and 30-day mortality were similar between the 2 groups. Recipients of DCD heart procured with DPP or NRP had similar severe PGD (LV/BiV) at 24 hours (9.4% vs 9.7%, p=0.93).

Conclusion: Severe PGD at 24 hours is higher among the DCD than DBD heart recipients, but Graft Dysfunction improves by 72 hours.