Risk evaluation using gene expression screening to monitor for acute cellular rejection in heart transplant recipients

Moayedi, Yasbanoo; Foroutan, Farid; Miller, Robert J.H.; Fan, Chun‐Po Steve; Posada, Juan Duero; Alhussein, Mosaad; Tremblay-Gravel, Maxime; Oro, Gabriela; Luikart, Helen; Yee, James; Shullo, M.; Khush, Kiran K.; Ross, Heather J.; Teuteberg, Jeffrey J.

doi:10.1016/j.healun.2018.09.004

Cited by 37 publications

(39 citation statements)

References 14 publications

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“…The natural progression of ACR grade 1R is not well defined, but we observed that the majority of patients did not progress to clinically overt rejection. In another recent study, 16 In the reference population of stable HT recipients free of rejection, dd-cfDNA is present at very low levels (median 0.07%). This is in contrast to stable kidney transplant recipients, in whom dd-cfDNA is detected at a median of 0.21% by using the AlloSure ® assay.…”

Section: Discussionmentioning

confidence: 87%

“…The size and design of the study estimated that the number of AR events was sufficient to demonstrate statistically significant performance characteristics of the assay. In another recent study,16 the composite outcome of death, retransplant, rejection with hemodynamic compromise (defined as LVEF ≤ 40% or a drop ≥ 25% compared with baseline or use of inotropic drugs or mechanical support), and nonspecific graft dysfunction (hemodynamic compromise without evidence of rejection) occurred in 103 patients during followup, and the occurrence of this composite endpoint at 1, 5, and 10 years was 4%, 15%, and 23%, respectively, whereas grade 1R ACR was found in 40.7% (456/1118) of biopsies performed between 2 and 6 months posttransplant. In the study population of patients who had received an HT at least 55 days before enrollment, dd-cfDNA testing detected AR with an AUC of 0.64 and provided an estimated NPV of 97.1% and PPV of 8.9%.…”

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confidence: 87%

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Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: A prospective multicenter study

Khush

Patel

Pinney

et al. 2019

American Journal of Transplantation

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166

175

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Standardized donor‐derived cell‐free DNA (dd‐cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this dd‐cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers and in a single‐center cohort of 33 patients at high risk for antibody‐mediated rejection (AMR). Plasma dd‐cfDNA was quantified by using targeted amplification and sequencing of a single nucleotide polymorphism panel. The dd‐cfDNA levels were correlated to paired events of biopsy‐based diagnosis of rejection. The median dd‐cfDNA was 0.07% in reference HT recipients (2164 samples) and 0.17% in samples classified as acute rejection (35 samples; P = .005). At a 0.2% threshold, dd‐cfDNA had a 44% sensitivity to detect rejection and a 97% negative predictive value. In the cohort at risk for AMR (11 samples), dd‐cfDNA levels were elevated 3‐fold in AMR compared with patients without AMR (99 samples, P = .004). The standardized dd‐cfDNA test identified acute rejection in samples from a broad population of HT recipients. The reported test performance characteristics will guide the next stage of clinical utility studies of the dd‐cfDNA assay.

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Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 87%

Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: A prospective multicenter study

Khush

Patel

Pinney

et al. 2019

American Journal of Transplantation

Self Cite

166

175

View full text Add to dashboard Cite

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“…Our low incidence of rejection, however, is consistent with real world data from the Outcomes Allomap Registry. 8 Next, we classified patients as following a TB surveillance versus a SS surveillance strategy based on review of clinical documentation. While treating cardiologist practice duration was a strong predictor of surveillance strategy, we cannot exclude the possibility that unmeasured covariates influenced provider practice pattern.…”

Section: Discussionmentioning

confidence: 99%

“…5 In the modern transplant era, the incidence of acute rejection is low beyond the first post-transplant year. 4,[6][7][8] However, guidelines continue to support routine EMBs for 5 years post-HT in higher risk patients and beyond 5 years per clinical judgement; GEPs are recommended in low risk patients 6 months to 5 years post-HT ( Table 1). 3 These recommendations have led to diverse surveillance practices given providers' concern about the potential consequences of rejection and their individual risk aversion.…”

Section: Introductionmentioning

confidence: 99%

“…In the modern transplant era, the incidence of acute rejection is low beyond the first post‐transplant year 4,6–8 . However, guidelines continue to support routine EMBs for 5 years post‐HT in higher risk patients and beyond 5 years per clinical judgement; GEPs are recommended in low risk patients 6 months to 5 years post‐HT ( Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

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Utility of routine evaluations for rejection in patients greater than 2 years after heart transplantation

2020

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Aims Guidelines support routine surveillance testing for rejection for at least 5 years after heart transplant (HT). In patients greater than 2 years post-HT, we examined which clinical characteristics predict continuation of routine surveillance studies, outcomes following discontinuation of routine surveillance, and the cost-effectiveness of different surveillance strategies. Methods and results We retrospectively identified subjects older than 18 who underwent a first HT at our centre from 2007 to 2016 and who survived ≥760 days (n = 217) post-HT. The clinical context surrounding all endomyocardial biopsies (EMBs) and gene expression profiles (GEPs) was reviewed to determine if studies were performed routinely or were triggered by a change in clinical status. Subjects were categorized as following a test-based surveillance (n = 159) or a signs/symptoms surveillance (n = 53) strategy based on treating cardiologist intent to continue routine studies after the second post-transplant year. A Markov model was constructed to compare two test-based surveillance strategies to a baseline strategy of discontinuing routine studies. One thousand twenty studies were performed; 835 were routine. Significant rejection was absent in 99.0% of routine EMBs and 99.8% of routine GEPs. The treating cardiologist's practice duration, patient age, and immunosuppressive regimen predicted surveillance strategy. There were no differences in outcomes between groups. Routine surveillance EMBs cost more and were marginally less effective than a strategy of discontinuing routine studies after 2 years; surveillance GEPs had an incremental cost-effectiveness ratio of $1.67 million/quality-adjusted life-year. Conclusions Acute asymptomatic rejection is rare after the second post-transplant year. Obtaining surveillance studies beyond the second post-transplant year is not cost-effective.

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Farr,

Mancini

2023

Textbook of Transplantation and Mechanical Support for End‐Stage Heart and Lung Disease

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Risk evaluation using gene expression screening to monitor for acute cellular rejection in heart transplant recipients

Cited by 37 publications

References 14 publications

Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: A prospective multicenter study

Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: A prospective multicenter study

Utility of routine evaluations for rejection in patients greater than 2 years after heart transplantation

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