Pub Date : 2025-12-04DOI: 10.1016/j.healun.2025.11.025
Alexander R. Berg BS, Aravind Krishnan MD, Elbert E. Heng MD, Ashley Y. Choi MD, MHS, Alyssa C. Garrison MS, Daniel I. Alnasir BS, Y. Chawannuch Ruaengsri MD, Yasuhiro Shudo MD, PHD, Y. Joseph Woo MD, John W. MacArthur MD
{"title":"Invited response letter","authors":"Alexander R. Berg BS, Aravind Krishnan MD, Elbert E. Heng MD, Ashley Y. Choi MD, MHS, Alyssa C. Garrison MS, Daniel I. Alnasir BS, Y. Chawannuch Ruaengsri MD, Yasuhiro Shudo MD, PHD, Y. Joseph Woo MD, John W. MacArthur MD","doi":"10.1016/j.healun.2025.11.025","DOIUrl":"10.1016/j.healun.2025.11.025","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"45 3","pages":"Pages 528-529"},"PeriodicalIF":6.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.1016/j.healun.2025.11.027
Cristiano Amarelli MD
{"title":"Beyond the edge","authors":"Cristiano Amarelli MD","doi":"10.1016/j.healun.2025.11.027","DOIUrl":"10.1016/j.healun.2025.11.027","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"45 3","pages":"Pages 334-336"},"PeriodicalIF":6.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145689532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-03DOI: 10.1016/j.healun.2025.11.021
Gregory I Snell, Bronwyn J Levvey
{"title":"The devil is in the details of Donation after Circulatory Death lung transplantation.","authors":"Gregory I Snell, Bronwyn J Levvey","doi":"10.1016/j.healun.2025.11.021","DOIUrl":"https://doi.org/10.1016/j.healun.2025.11.021","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-29DOI: 10.1016/j.healun.2025.11.032
Eileen M. Hsich MD , Marc K. Halushka MD, PhD
{"title":"Multimodal molecular testing for heart transplant recipients—is it actionable yet?","authors":"Eileen M. Hsich MD , Marc K. Halushka MD, PhD","doi":"10.1016/j.healun.2025.11.032","DOIUrl":"10.1016/j.healun.2025.11.032","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"45 3","pages":"Pages 401-402"},"PeriodicalIF":6.0,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1016/j.healun.2025.11.031
Hakim Ghani , Joanna Pepke-Zaba
{"title":"Old clots, new questions — the anticoagulation saga continues in chronic thromboembolic pulmonary hypertension","authors":"Hakim Ghani , Joanna Pepke-Zaba","doi":"10.1016/j.healun.2025.11.031","DOIUrl":"10.1016/j.healun.2025.11.031","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"45 3","pages":"Pages 457-459"},"PeriodicalIF":6.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1016/j.healun.2025.10.022
Seth A. Hollander MD , Stephanie Hsiao , Anubodh S. Varshney , Helen Luikart , Alireza Raissadati , Daniel Bernstein , Michael Ma , Kari Wujcik , Lynsey Barkoff , John Dykes , Donna Lee , David N. Rosenthal
Purpose
Long-term outcomes after pediatric heart transplant (pHT) are rarely reported owing to young programs and loss of follow-up after transition to adult care. We leveraged our program age, center volume, and linked electronic medical record to analyze 50-year outcomes after pHT, including events after adult care transfer.
Methods
Retrospective review of all pHT over 50 years at Stanford (August 19, 1974 to August 19, 2024). Patient characteristics and posttransplant outcomes, including death, retransplant, and subsequent kidney transplantation, were ascertained from the pediatric and adult electronic medical records, public records, and personal communication with other centers.
Results
There were 567 pHTs in 540 patients. Status as of August 19, 2024 was confirmed for 526 (97%),11 (2%) had partial follow-up, and 3 were missing. Over 1,888,341 follow-up days, 50 (9%) received a second heart transplant (27 pediatric, 23 adult) after a median of 9 (5, 14) years; 3 (1%) received a third heart transplant; 6 (1%) received a subsequent kidney transplant, and 212 (39%) died (172 pediatric, 40 adult). Median survival was 16.7 years; survival improved in successive eras (p<0.001).
Conclusion
This linked analysis of pediatric and adult programs shows excellent long-term pHT outcomes with median survival exceeding 15 years and improving. Nearly half of retransplants occur after transfer; subsequent kidney transplant occurs infrequently.
{"title":"Fifty-year pediatric heart transplant outcomes: A pediatric-adult center linked analysis","authors":"Seth A. Hollander MD , Stephanie Hsiao , Anubodh S. Varshney , Helen Luikart , Alireza Raissadati , Daniel Bernstein , Michael Ma , Kari Wujcik , Lynsey Barkoff , John Dykes , Donna Lee , David N. Rosenthal","doi":"10.1016/j.healun.2025.10.022","DOIUrl":"10.1016/j.healun.2025.10.022","url":null,"abstract":"<div><h3>Purpose</h3><div>Long-term outcomes after pediatric heart transplant (pHT) are rarely reported owing to young programs and loss of follow-up after transition to adult care. We leveraged our program age, center volume, and linked electronic medical record to analyze 50-year outcomes after pHT, including events after adult care transfer.</div></div><div><h3>Methods</h3><div>Retrospective review of all pHT over 50 years at Stanford (August 19, 1974 to August 19, 2024). Patient characteristics and posttransplant outcomes, including death, retransplant, and subsequent kidney transplantation, were ascertained from the pediatric and adult electronic medical records, public records, and personal communication with other centers.</div></div><div><h3>Results</h3><div>There were 567 pHTs in 540 patients. Status as of August 19, 2024 was confirmed for 526 (97%),11 (2%) had partial follow-up, and 3 were missing. Over 1,888,341 follow-up days, 50 (9%) received a second heart transplant (27 pediatric, 23 adult) after a median of 9 (5, 14) years; 3 (1%) received a third heart transplant; 6 (1%) received a subsequent kidney transplant, and 212 (39%) died (172 pediatric, 40 adult). Median survival was 16.7 years; survival improved in successive eras (<em>p</em><0.001).</div></div><div><h3>Conclusion</h3><div>This linked analysis of pediatric and adult programs shows excellent long-term pHT outcomes with median survival exceeding 15 years and improving. Nearly half of retransplants occur after transfer; subsequent kidney transplant occurs infrequently.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"45 3","pages":"Pages 485-491"},"PeriodicalIF":6.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1016/j.healun.2025.11.022
Kyle Saysana MD , Nelson Chow BS , Shi Huang PhD , Benjamin French MD , Raymond Dieter MD , Ayeshia Ali BS , Eric Farber-Eger BS , Quinn S. Wells MD, PharmD , Hasan K. Siddiqi MD , David W. Bearl MD , Kelly H. Schlendorf MD, MHS , Kaushik Amancherla MD, MSCI
Background
Uncovering sex-based differences in immunologic outcomes following heart transplantation (HT) can inform risk stratification and precision immunosuppressive strategies. However, granular clinical-translational understanding of sex-specific molecular risk in the modern era is lacking. Here, we investigate the relationship between sex, acute rejection, and cardiac allograft vasculopathy (CAV) in adults and children following HT. We then decode cell-specific gene expression patterns in healthy individuals and HT recipients to identify discordant pathways that inform immunologic risk.
Methods
We studied 833 adult and pediatric HT recipients to delineate the risk of donor-specific antibody (DSA) formation, acute rejection, and angiographic CAV between males and females. Next, using publicly available single-cell RNA-sequencing (scRNA-seq) data in circulating immune cells of healthy individuals (N = 981) and an HT-specific scRNA-seq dataset (N = 40), we conducted sex-stratified differential gene expression and functional enrichment analyses.
Results
Among 833 HT recipients (694 adults, 139 children; overall 32.8% female), no significant differences in acute rejection were identified between males and females. Adult females were less likely to develop angiographic CAV (HR 0.58, 95% CI 0.42-0.79). In healthy individuals, scRNA-seq recapitulated enrichment for broad autoimmune/inflammatory pathways in females. However, this was inverted following HT, with male recipients exhibiting upregulation translational/ribosomal machinery and cytokine sensing/signaling in a cell-specific fashion, along with enrichment for autoimmune disease pathways. CAV-associated gene sets were preferentially male-skewed in memory T cells.
Discussion
Despite similar rates of acute rejection, adult females were less likely to develop angiographic CAV. Differences between healthy and post-HT individuals identified molecular biases that may drive chronic low-grade inflammation, favoring CAV development in males. Additional studies are needed to validate these findings.
了解心脏移植（HT）后免疫结果的性别差异可以为风险分层和精确的免疫抑制策略提供信息。然而，在现代，缺乏对性别特异性分子风险的细粒度临床转化理解。在这里，我们研究性别、急性排斥反应和成人和儿童同种异体心脏移植后血管病变（CAV）之间的关系。然后，我们解码健康个体和HT受体的细胞特异性基因表达模式，以识别告知免疫风险的不一致途径。方法我们研究了833名成人和儿童HT受体，以描述男性和女性之间供体特异性抗体（DSA）形成、急性排斥反应和血管造影CAV的风险。接下来，利用健康个体循环免疫细胞（N = 981）中公开的单细胞rna测序（scRNA-seq）数据和ht特异性scRNA-seq数据集（N = 40），我们进行了性别分层的差异基因表达和功能富集分析。结果在833例接受HT治疗的患者中（成人694例，儿童139例，女性32.8%），男性和女性的急性排斥反应无显著差异。成年女性发生血管造影CAV的可能性较低（HR 0.58, 95% CI 0.42-0.79）。在健康个体中，scRNA-seq重现了女性广泛的自身免疫/炎症途径的富集。然而，这种情况在HT后发生逆转，男性受体表现出翻译/核糖体机制和细胞因子感知/信号传导以细胞特异性方式上调，同时自身免疫性疾病途径富集。cav相关基因组在记忆T细胞中优先偏向男性。尽管急性排斥反应的发生率相似，但成年女性发生血管造影CAV的可能性较小。健康个体和ht后个体之间的差异确定了可能驱动慢性低度炎症的分子偏差，有利于男性CAV的发展。需要进一步的研究来证实这些发现。
{"title":"Sex-biased immune rewiring may underlie reduced risk for cardiac allograft vasculopathy in females following heart transplantation","authors":"Kyle Saysana MD , Nelson Chow BS , Shi Huang PhD , Benjamin French MD , Raymond Dieter MD , Ayeshia Ali BS , Eric Farber-Eger BS , Quinn S. Wells MD, PharmD , Hasan K. Siddiqi MD , David W. Bearl MD , Kelly H. Schlendorf MD, MHS , Kaushik Amancherla MD, MSCI","doi":"10.1016/j.healun.2025.11.022","DOIUrl":"10.1016/j.healun.2025.11.022","url":null,"abstract":"<div><h3>Background</h3><div>Uncovering sex-based differences in immunologic outcomes following heart transplantation (HT) can inform risk stratification and precision immunosuppressive strategies. However, granular clinical-translational understanding of sex-specific molecular risk in the modern era is lacking. Here, we investigate the relationship between sex, acute rejection, and cardiac allograft vasculopathy (CAV) in adults and children following HT. We then decode cell-specific gene expression patterns in healthy individuals and HT recipients to identify discordant pathways that inform immunologic risk.</div></div><div><h3>Methods</h3><div>We studied 833 adult and pediatric HT recipients to delineate the risk of donor-specific antibody (DSA) formation, acute rejection, and angiographic CAV between males and females. Next, using publicly available single-cell RNA-sequencing (scRNA-seq) data in circulating immune cells of healthy individuals (<em>N</em> = 981) and an HT-specific scRNA-seq dataset (<em>N</em> = 40), we conducted sex-stratified differential gene expression and functional enrichment analyses.</div></div><div><h3>Results</h3><div>Among 833 HT recipients (694 adults, 139 children; overall 32.8% female), no significant differences in acute rejection were identified between males and females. Adult females were less likely to develop angiographic CAV (HR 0.58, 95% CI 0.42-0.79). In healthy individuals, scRNA-seq recapitulated enrichment for broad autoimmune/inflammatory pathways in females. However, this was inverted following HT, with male recipients exhibiting upregulation translational/ribosomal machinery and cytokine sensing/signaling in a cell-specific fashion, along with enrichment for autoimmune disease pathways. CAV-associated gene sets were preferentially male-skewed in memory T cells.</div></div><div><h3>Discussion</h3><div>Despite similar rates of acute rejection, adult females were less likely to develop angiographic CAV. Differences between healthy and post-HT individuals identified molecular biases that may drive chronic low-grade inflammation, favoring CAV development in males. Additional studies are needed to validate these findings.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"45 3","pages":"Pages 365-374"},"PeriodicalIF":6.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1016/j.healun.2025.11.014
David P. Jenkins MB BS. , Sofija Cerovic M.D., MSc , Dénes Csonka PharmD, PhD , Hossein-Ardeschir Ghofrani M.D. , Stefan Guth M.D. , Gustavo A. Heresi M.D. , Marc Humbert M.D, PhD. , Noormaa Jaumdally MSc , Zhi-Cheng Jing M.D. , Gabriela Lack PhD, MSc Pharm , Michael M. Madani M.D., FACS , Hiromi Matsubara M.D. , Eckhard Mayer M.D. , Erin McGuire PharmD, MBA , Nick H. Kim M.D.
Background
In a phase 2 study of inoperable chronic thromboembolic pulmonary hypertension (CTEPH), macitentan 10 mg improved hemodynamics and exercise capacity.
Methods
MACiTEPH (NCT04271475) was a prospective, double-blind, placebo-controlled, phase 3 study. Adult patients with inoperable CTEPH (with/without balloon pulmonary angioplasty [BPA]) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA) (with/without BPA) were randomized 1:1 to macitentan 75 mg or placebo once daily. Primary endpoint was change from baseline to Week 28 in 6-minute walk distance (6MWD).
Results
Following a pre-planned interim analysis, the study was stopped for futility. 127 patients were randomized, predominantly with inoperable CTEPH with BPA (36.2%) or persistent/recurrent CTEPH after PEA without BPA (30.7%). The majority (81.9%) were receiving pulmonary hypertension (PH)-specific therapy at baseline. 47 patients in the macitentan 75 mg and 48 in the placebo group had Week 28 assessments. Primary endpoint was not met; mean change in 6MWD from baseline to Week 28 versus placebo was −16.1 m (95% confidence limit: −32.3, 0.16). Clinical worsening events occurred in 6.3% and 14.3% of patients in the macitentan 75 mg and placebo groups, respectively. A slightly higher proportion of the macitentan 75 mg group had ≥1 adverse event (AE) or serious AE versus placebo; no pattern was identified. More patients in macitentan 75 mg versus placebo group discontinued treatment due to an AE (21.9% versus 7.9%, respectively).
Conclusions
MACiTEPH was discontinued for futility, as no treatment effect on 6MWD (primary endpoint) was observed. Despite the higher discontinuation rate in the macitentan 75 mg group, no unexpected safety signals were observed in CTEPH patients.
{"title":"Results of the MACiTEPH study of macitentan for the treatment of inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension","authors":"David P. Jenkins MB BS. , Sofija Cerovic M.D., MSc , Dénes Csonka PharmD, PhD , Hossein-Ardeschir Ghofrani M.D. , Stefan Guth M.D. , Gustavo A. Heresi M.D. , Marc Humbert M.D, PhD. , Noormaa Jaumdally MSc , Zhi-Cheng Jing M.D. , Gabriela Lack PhD, MSc Pharm , Michael M. Madani M.D., FACS , Hiromi Matsubara M.D. , Eckhard Mayer M.D. , Erin McGuire PharmD, MBA , Nick H. Kim M.D.","doi":"10.1016/j.healun.2025.11.014","DOIUrl":"10.1016/j.healun.2025.11.014","url":null,"abstract":"<div><h3>Background</h3><div>In a phase 2 study of inoperable chronic thromboembolic pulmonary hypertension (CTEPH), macitentan 10 mg improved hemodynamics and exercise capacity.</div></div><div><h3>Methods</h3><div>MACiTEPH (NCT04271475) was a prospective, double-blind, placebo-controlled, phase 3 study. Adult patients with inoperable CTEPH (with/without balloon pulmonary angioplasty [BPA]) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA) (with/without BPA) were randomized 1:1 to macitentan 75 mg or placebo once daily. Primary endpoint was change from baseline to Week 28 in 6-minute walk distance (6MWD).</div></div><div><h3>Results</h3><div>Following a pre-planned interim analysis, the study was stopped for futility. 127 patients were randomized, predominantly with inoperable CTEPH with BPA (36.2%) or persistent/recurrent CTEPH after PEA without BPA (30.7%). The majority (81.9%) were receiving pulmonary hypertension (PH)-specific therapy at baseline. 47 patients in the macitentan 75 mg and 48 in the placebo group had Week 28 assessments. Primary endpoint was not met; mean change in 6MWD from baseline to Week 28 versus placebo was −16.1 m (95% confidence limit: −32.3, 0.16). Clinical worsening events occurred in 6.3% and 14.3% of patients in the macitentan 75 mg and placebo groups, respectively. A slightly higher proportion of the macitentan 75 mg group had ≥1 adverse event (AE) or serious AE versus placebo; no pattern was identified. More patients in macitentan 75 mg versus placebo group discontinued treatment due to an AE (21.9% versus 7.9%, respectively).</div></div><div><h3>Conclusions</h3><div>MACiTEPH was discontinued for futility, as no treatment effect on 6MWD (primary endpoint) was observed. Despite the higher discontinuation rate in the macitentan 75 mg group, no unexpected safety signals were observed in CTEPH patients.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"45 3","pages":"Pages 442-451"},"PeriodicalIF":6.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145583802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1016/j.healun.2025.11.013
Jeff Teuteberg MD , Snehal Patel MD , David A. Baran MD , Palak Shah MD,MS , Gabriel Sayer MD , Ann B. Nguyen MD , Ashwin Ravichandran MD, MPH , Shelley Hall MD , Sean Pinney MD , Eugene DePasquale MD , Nirav Raval MD , Jeremy Kobulnik MD,MHSc , Chun-Po Steve Fan PhD, PStat , Kris Oreschak PhD , Sijia Wang MS , Kiran K. Khush MD, MAS , Nir Uriel MD
Background
Multimodal molecular testing with gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) is increasingly used for rejection surveillance, but less is known about their joint ability to predict future clinical events.
Methods
We evaluated 1934 heart transplant recipients from the Surveillance HeartCare Outcomes Registry. Risk was assessed two ways. First, based on the most abnormal GEP/dd-cfDNA result during months 2–6 post-transplant, the incidence of graft dysfunction (GD) and cardiovascular (CV) death was assessed in the subsequent 12 months. Second, we analyzed the 30-day incidence of GD and CV death following individual GEP/dd-cfDNA results between 2-months and 5-years post-transplant.
Results
GD and CV death occurred in 166 and 19 patients during the 12-month follow-up period, respectively. In months 2 to 6 post-transplant, those with GEP+/dd-cfDNA+ had the highest incidence of GD or CV death (15.5%) in the following year, with a HR of 1.59 (1.08–2.32; p=0.017) versus those without GEP+/dd-cfDNA+. When limited to those without evidence of rejection in months 2 to 6, the GEP+/dd-cfDNA+ group had the highest incidence of GD or CV death (14.6% vs 5.1–8.7%; p=0.039). A single GEP+/dd-cfDNA+, versus a GEP-/dd-cfDNA- result, conferred a 3-fold increase in the 30-day incidence rate of GD or CV death (adjusted IRR 3.12; 95% CI 1.37–7.10; p=0.007).
Conclusions
Patients with dual positive GEP and dd-cfDNA are at increased risk for subsequent GD and CV death, even in the absence of histological evidence of rejection, indicating circulating multimodal molecular evidence of rejection provides prognostic information not detected by histology.
基因表达谱（GEP）和供体来源无细胞DNA （dd-cfDNA）的多模态分子检测越来越多地用于排斥反应监测，但对它们预测未来临床事件的联合能力知之甚少。方法：我们评估了来自心脏保健结局监测登记处的1934例心脏移植受者。风险评估有两种方式。首先，根据移植后2-6个月内最异常的GEP/dd-cfDNA结果，评估随后12个月内移植物功能障碍（GD）和心血管（CV）死亡的发生率。其次，我们分析了移植后2个月至5年个体GEP/dd-cfDNA结果后30天GD和CV死亡发生率。结果随访12个月，gd死亡166例，CV死亡19例。移植后2 ~ 6个月，GEP+/dd-cfDNA+组次年GD或CV死亡发生率最高（15.5%），与未GEP+/dd-cfDNA+组相比，HR为1.59 （1.08 ~ 2.32;p=0.017）。当局限于2 - 6个月无排斥反应证据的患者时，GEP+/dd-cfDNA+组的GD或CV死亡发生率最高（14.6% vs 5.1-8.7%; p=0.039）。单一的GEP+/dd-cfDNA+结果与GEP-/dd-cfDNA-结果相比，30天GD或CV死亡发生率增加3倍（校正IRR 3.12; 95% CI 1.37-7.10; p=0.007）。结论GEP和dd-cfDNA双重阳性的患者，即使在没有排斥反应的组织学证据的情况下，后续GD和CV死亡的风险也会增加，表明循环的多模态排斥反应分子证据提供了组织学未检测到的预后信息。
{"title":"Multimodal molecular testing provides prognostic value for heart transplant recipients","authors":"Jeff Teuteberg MD , Snehal Patel MD , David A. Baran MD , Palak Shah MD,MS , Gabriel Sayer MD , Ann B. Nguyen MD , Ashwin Ravichandran MD, MPH , Shelley Hall MD , Sean Pinney MD , Eugene DePasquale MD , Nirav Raval MD , Jeremy Kobulnik MD,MHSc , Chun-Po Steve Fan PhD, PStat , Kris Oreschak PhD , Sijia Wang MS , Kiran K. Khush MD, MAS , Nir Uriel MD","doi":"10.1016/j.healun.2025.11.013","DOIUrl":"10.1016/j.healun.2025.11.013","url":null,"abstract":"<div><h3>Background</h3><div>Multimodal molecular testing with gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) is increasingly used for rejection surveillance, but less is known about their joint ability to predict future clinical events.</div></div><div><h3>Methods</h3><div>We evaluated 1934 heart transplant recipients from the Surveillance HeartCare Outcomes Registry. Risk was assessed two ways. First, based on the most abnormal GEP/dd-cfDNA result during months 2–6 post-transplant, the incidence of graft dysfunction (GD) and cardiovascular (CV) death was assessed in the subsequent 12 months. Second, we analyzed the 30-day incidence of GD and CV death following individual GEP/dd-cfDNA results between 2-months and 5-years post-transplant.</div></div><div><h3>Results</h3><div>GD and CV death occurred in 166 and 19 patients during the 12-month follow-up period, respectively. In months 2 to 6 post-transplant, those with GEP+/dd-cfDNA+ had the highest incidence of GD or CV death (15.5%) in the following year, with a HR of 1.59 (1.08–2.32; p=0.017) versus those without GEP+/dd-cfDNA+. When limited to those without evidence of rejection in months 2 to 6, the GEP+/dd-cfDNA+ group had the highest incidence of GD or CV death (14.6% vs 5.1–8.7%; p=0.039). A single GEP+/dd-cfDNA+, versus a GEP-/dd-cfDNA- result, conferred a 3-fold increase in the 30-day incidence rate of GD or CV death (adjusted IRR 3.12; 95% CI 1.37–7.10; p=0.007).</div></div><div><h3>Conclusions</h3><div>Patients with dual positive GEP and dd-cfDNA are at increased risk for subsequent GD and CV death, even in the absence of histological evidence of rejection, indicating circulating multimodal molecular evidence of rejection provides prognostic information not detected by histology.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"45 3","pages":"Pages 388-400"},"PeriodicalIF":6.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1016/j.healun.2025.11.023
Megan Neely PhD , Emmanuel Mongodin PhD , Bryan A. Whitson MD, PhD , Ramsey R. Hachem MD , Michaela R. Anderson MD, MS , Courtney Frankel MS , Michelle L. Oyster MS , Ciara M. Shaver MD, PhD , Eric D. Morrell MD, MA , Meghan Aversa MD , Allyn M. Damman MA , Jason Christie MD, MSCE , Scott M. Palmer MD, MHS , on behalf of the Lung Transplant Consortium Investigators and Steering Committee
The Lung Transplant Consortium (LTC), sponsored by the National Heart, Lung, and Blood Institute (NHLBI) is a 20-center collaboration among lung transplant programs in North America conducting both smaller multicenter projects and one consortium-wide prospective observational cohort study called the Prospective Multicenter Research on Donor and Recipient Management Strategies to Improve Lung Transplant Outcomes (PROMISE) Lung Study—for more information about the LTC, visit their website: https://lungtransplantconsortium.org/. The LTC conducted a meeting in April 2025 to strategize how to maximize the benefits of the PROMISE study to advance the field of lung transplant. This paper summarizes the key themes that emerged from the meeting: leveraging PROMISE data elements, including biomarkers, imaging, and PROs; clinical syndrome and consensus definitions; variation in management and management strategies; and future interventional trials leveraging the PROMISE consortium. The PROMISE study will serve as the platform for establishing best practices in lung transplant, inform the validity of newly identified syndromes, and support analysis of patient-reported outcomes, image data, and biosamples. The PROMISE study and LTC create a critically needed research platform and multicenter collaborative structure that may be adapted to conduct future multicenter clinical trials that will advance lung transplant medicine.
{"title":"The NHLBI lung transplant consortium 2025 steering committee report: Strategies to maximize the use of the consortium for advancing lung transplantation","authors":"Megan Neely PhD , Emmanuel Mongodin PhD , Bryan A. Whitson MD, PhD , Ramsey R. Hachem MD , Michaela R. Anderson MD, MS , Courtney Frankel MS , Michelle L. Oyster MS , Ciara M. Shaver MD, PhD , Eric D. Morrell MD, MA , Meghan Aversa MD , Allyn M. Damman MA , Jason Christie MD, MSCE , Scott M. Palmer MD, MHS , on behalf of the Lung Transplant Consortium Investigators and Steering Committee","doi":"10.1016/j.healun.2025.11.023","DOIUrl":"10.1016/j.healun.2025.11.023","url":null,"abstract":"<div><div>The Lung Transplant Consortium (LTC), sponsored by the National Heart, Lung, and Blood Institute (NHLBI) is a 20-center collaboration among lung transplant programs in North America conducting both smaller multicenter projects and one consortium-wide prospective observational cohort study called the Prospective Multicenter Research on Donor and Recipient Management Strategies to Improve Lung Transplant Outcomes (PROMISE) Lung Study—for more information about the LTC, visit their website: <span><span>https://lungtransplantconsortium.org/</span><svg><path></path></svg></span>. The LTC conducted a meeting in April 2025 to strategize how to maximize the benefits of the PROMISE study to advance the field of lung transplant. This paper summarizes the key themes that emerged from the meeting: leveraging PROMISE data elements, including biomarkers, imaging, and PROs; clinical syndrome and consensus definitions; variation in management and management strategies; and future interventional trials leveraging the PROMISE consortium. The PROMISE study will serve as the platform for establishing best practices in lung transplant, inform the validity of newly identified syndromes, and support analysis of patient-reported outcomes, image data, and biosamples. The PROMISE study and LTC create a critically needed research platform and multicenter collaborative structure that may be adapted to conduct future multicenter clinical trials that will advance lung transplant medicine.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"45 3","pages":"Pages 317-323"},"PeriodicalIF":6.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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