Acute cellular rejection after heart transplantation: validation of HEARTBiT, a transcriptomic biomarker.

IF 45.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

European Heart Journal Pub Date : 2026-09-29 DOI:10.1093/eurheartj/ehag751

Casey P Shannon, Sara Assadian, Ashwini Rajasekaran, Chengliang Yang, Estefanía Espín, Le Lam, Robert Balshaw, Michael A Seidman, Chi K Lai, Heather J Ross, Marshall P Hyden, Sharon S Y Chih, Mustafa Toma, Bruce M McManus, Raymond T Ng, Scott J Tebbutt

{"title":"Acute cellular rejection after heart transplantation: validation of HEARTBiT, a transcriptomic biomarker.","authors":"Casey P Shannon, Sara Assadian, Ashwini Rajasekaran, Chengliang Yang, Estefanía Espín, Le Lam, Robert Balshaw, Michael A Seidman, Chi K Lai, Heather J Ross, Marshall P Hyden, Sharon S Y Chih, Mustafa Toma, Bruce M McManus, Raymond T Ng, Scott J Tebbutt","doi":"10.1093/eurheartj/ehag751","DOIUrl":null,"url":null,"abstract":"Background and aims: Acute cellular rejection (ACR) risk is highest within 60 days of heart transplantation (HTx), yet existing minimally invasive surveillance tools lack validation for this high-risk period. This study prospectively validated the diagnostic accuracy of HEARTBiT, a transcriptomic biomarker for detecting moderate-to-severe ACR, including during the early post-operative period.Methods: This prospective diagnostic accuracy study (NCT03575910) enrolled consecutive adult HTx recipients at four tertiary clinical centres. The diagnostic performance of HEARTBiT was evaluated in 336 visits from 117 participants against centralized expert consensus panel endomyocardial biopsy grades. An exploratory analysis of 246 serial visits from 31 participants evaluated the prognostic potential of tracking individual transcriptomic trajectories over time.Results: HEARTBiT accurately detected moderate-to-severe ACR (ISHLT ≥2R) with an overall area under the curve (AUC) of 0.78 [95% confidence interval (CI) 0.70-0.86]. Performance was stable early post-HTx (≤60 days: AUC = 0.78, 95% CI 0.65-0.90) and beyond 60 days (AUC = 0.80, 95% CI 0.72-0.87). Prioritizing high sensitivity (89% early, 100% late; corresponding to ≤1 missed ACR overall) yielded a specificity of 56% in the early period (≤60 days) and 49% beyond 60 days using the pre-specified cutoff (>0.54). Alternatively, adopting an exploratory time-varying threshold (>0.68) beyond 60 days yielded 83% sensitivity and 76% specificity. Importantly, HEARTBiT scores increased weeks before histological detection of ACR by tissue biopsy (slope-based AUC = 0.78, 95% CI 0.60-0.96).Conclusions: HEARTBiT provides a reliable, minimally invasive rule-out signal for moderate-to-severe ACR across the first year post-HTx, particularly during the high-risk early post-operative period. Serial tracking of HEARTBiT score trajectories has potential for prognosis of progression to ACR. These findings support the clinical utility of this biomarker in safely sparing more than 50% of protocol surveillance endomyocardial biopsies.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":""},"PeriodicalIF":45.3000,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Heart Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/eurheartj/ehag751","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

Abstract

Background and aims: Acute cellular rejection (ACR) risk is highest within 60 days of heart transplantation (HTx), yet existing minimally invasive surveillance tools lack validation for this high-risk period. This study prospectively validated the diagnostic accuracy of HEARTBiT, a transcriptomic biomarker for detecting moderate-to-severe ACR, including during the early post-operative period.

Methods: This prospective diagnostic accuracy study (NCT03575910) enrolled consecutive adult HTx recipients at four tertiary clinical centres. The diagnostic performance of HEARTBiT was evaluated in 336 visits from 117 participants against centralized expert consensus panel endomyocardial biopsy grades. An exploratory analysis of 246 serial visits from 31 participants evaluated the prognostic potential of tracking individual transcriptomic trajectories over time.

Results: HEARTBiT accurately detected moderate-to-severe ACR (ISHLT ≥2R) with an overall area under the curve (AUC) of 0.78 [95% confidence interval (CI) 0.70-0.86]. Performance was stable early post-HTx (≤60 days: AUC = 0.78, 95% CI 0.65-0.90) and beyond 60 days (AUC = 0.80, 95% CI 0.72-0.87). Prioritizing high sensitivity (89% early, 100% late; corresponding to ≤1 missed ACR overall) yielded a specificity of 56% in the early period (≤60 days) and 49% beyond 60 days using the pre-specified cutoff (>0.54). Alternatively, adopting an exploratory time-varying threshold (>0.68) beyond 60 days yielded 83% sensitivity and 76% specificity. Importantly, HEARTBiT scores increased weeks before histological detection of ACR by tissue biopsy (slope-based AUC = 0.78, 95% CI 0.60-0.96).

Conclusions: HEARTBiT provides a reliable, minimally invasive rule-out signal for moderate-to-severe ACR across the first year post-HTx, particularly during the high-risk early post-operative period. Serial tracking of HEARTBiT score trajectories has potential for prognosis of progression to ACR. These findings support the clinical utility of this biomarker in safely sparing more than 50% of protocol surveillance endomyocardial biopsies.

查看原文本刊更多论文

心脏移植后的急性细胞排斥反应：验证HEARTBiT，一个转录组生物标志物。

背景和目的：急性细胞排斥反应（ACR）风险在心脏移植（HTx） 60天内最高，但现有的微创监测工具缺乏对这一高风险时期的验证。这项研究前瞻性地验证了HEARTBiT的诊断准确性，HEARTBiT是一种检测中度至重度ACR的转录组生物标志物，包括术后早期。方法：这项前瞻性诊断准确性研究（NCT03575910）纳入了四个三级临床中心的连续成人HTx接受者。在117名参与者的336次就诊中，对HEARTBiT的诊断性能进行了评估，对照集中的专家共识小组心内膜肌活检评分。一项对来自31名参与者的246次连续访问的探索性分析评估了随时间跟踪个体转录组轨迹的预后潜力。结果：HEARTBiT准确检测中重度ACR (ISHLT≥2R)，总体曲线下面积（AUC）为0.78[95%置信区间（CI） 0.70-0.86]。htx术后早期（≤60天：AUC = 0.78, 95% CI 0.65-0.90）和60天后（AUC = 0.80, 95% CI 0.72-0.87）表现稳定。优先考虑高灵敏度（89%早期，100%晚期，对应于≤1遗漏ACR总体），使用预先指定的截止（>0.54），早期（≤60天）的特异性为56%，超过60天的特异性为49%。另外，如果采用60天以上的探索性时变阈值（>0.68），则灵敏度为83%，特异性为76%。重要的是，在组织活检检测ACR的组织学前几周，HEARTBiT评分增加（斜率AUC = 0.78, 95% CI 0.60-0.96）。结论：HEARTBiT为htx术后第一年的中重度ACR提供了可靠的、微创的排除信号，特别是在高危的术后早期。连续跟踪HEARTBiT评分轨迹有可能预测进展为ACR的预后。这些发现支持该生物标志物的临床应用，可以安全地节省超过50%的方案监测心内膜活组织检查。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

European Heart Journal 医学-心血管系统

CiteScore

39.30

自引率

6.90%

发文量

3942

审稿时长

1 months

期刊介绍： The European Heart Journal is a renowned international journal that focuses on cardiovascular medicine. It is published weekly and is the official journal of the European Society of Cardiology. This peer-reviewed journal is committed to publishing high-quality clinical and scientific material pertaining to all aspects of cardiovascular medicine. It covers a diverse range of topics including research findings, technical evaluations, and reviews. Moreover, the journal serves as a platform for the exchange of information and discussions on various aspects of cardiovascular medicine, including educational matters. In addition to original papers on cardiovascular medicine and surgery, the European Heart Journal also presents reviews, clinical perspectives, ESC Guidelines, and editorial articles that highlight recent advancements in cardiology. Additionally, the journal actively encourages readers to share their thoughts and opinions through correspondence.