Journal of Heart and Lung Transplantation最新文献

Background: A pediatric national heart review board (NHRB) and exception guidance document to standardize decision-making were implemented in 2021 to reduce variability and ensure equity in status exceptions for pediatric candidates. We evaluated the hypothesis that these changes decreased center variability and racial disparities within the granted exceptions.

Methods: Guidance document and pediatric NHRB were operational by February and June 2021, respectively. Candidates were stratified by listing date into: Era 1, pre-policy changes (July 2018 - June 2020) and Era 2, post-policy changes (July 2021 - June 2023). Mixed effects logistic regression models evaluated individual and center-level predictors of receiving status 1A and 1B exceptions (E) pre- and post-policy implementation.

Results: Of 1,275 Era 1 listees, 15% received a 1A(E), with significant center variation. Black listees had lower likelihood of receiving 1A(E) (OR 0.57 [95% CI 0.34 - 0.94]), controlling for age, diagnosis, and center effects. Among 1,369 Era 2 listees, 14% received status 1A(E). Race was not associated with 1A(E), when controlling for the same variables, and center effect was not significant. While children listed 1B(E) increased from 12% to 16% from Era 1 to Era 2, in both eras, Black children were less likely to receive 1B(E) (OR 0.56 [95% CI 0.33 - 0.94) in Era 1, and 0.56 [0.34 - 0.91]) in Era 2). Center effect was significant in both eras.

Conclusions: Since implementing exception guidance and a pediatric review board, variation by center and patient race/ethnicity in 1A exceptions has been reduced. Center variation and racial disparities persist among 1B exceptions.

Background: Liquid biopsy offers a potential alternative to decrease or eliminate endomyocardial biopsy for diagnosing allograft rejection. p-element-induced wimpy testis-interacting RNAs (piRNAs) are novel and promising disease biomarkers for their intrinsic characteristics such as stability in body fluids; however, their role in allograft rejection remains unexplored.

Methods: A training set based on small RNA sequencing technology was performed to identify piRNAs in endomyocardial tissue (n = 8) and serum samples (n = 40) from patients following heart transplantation. A validation set of the potential piRNAs identified in the training study was conducted in an independent larger cohort for the detection of acute cellular rejection (ACR, n = 105) and antibody-mediated rejection (AMR, n = 61).

Results: We identified 20,292 piRNAs in endomyocardial tissue and 24,602 piRNAs in serum samples from patients following heart transplantation. We identified 7 piRNAs with a coincident expression profile in both types of samples and potential capacity for the noninvasive detection of cardiac rejection. Validation in a large independent cohort demonstrated that a panel of these piRNAs showed excellent performance for detecting grade ≥2R ACR (area under the receiver operating characteristic curve [AUC] = 0.819; p < 0.0001) and grade 1R ACR (AUC = 0.721; p = 0.001). Furthermore, our piRNA panel showed a potential discrimination ability of pAMR2 (AUC = 0.967; p < 0.0001).

Conclusions: To the best of knowledge, this study is the first to report the presence of piRNAs in both endomyocardial tissue and serum samples of patients after heart transplant, including their association with allograft rejection events. We propose a novel piRNA panel for the detection of cardiac allograft rejection.

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.