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

Abstract

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.

Plasma Donor-derived Cell-free DNA Levels Are Increased During Acute Cellular Rejection After Lung Transplant: Pilot Data

“…We speculate that assessment of dd-cfDNA in the context of obstructive and restrictive phenotypes of CLAD 10 may provide additional insights into pathophysiology and treatment algorithms. Finally, the era LARGO preceded the elucidation of AMR in LT, 11 therefore, further assessment of dd-cfDNA in this spectrum of rejection, would be warranted as increased dd-cfDNA has been previously reported with AMR after kidney, 12 heart, 13 , 14 and LT. 2 …”

Pediatric heart transplantation: how to manage problems affecting long-term outcomes?

“…The reported test performance characteristics will guide the next stage of clinical utility studies of the ddcf DNA assay. 31,32)…”

Circulating cell-free DNA levels are associated with adverse outcomes in heart failure: testing liquid biopsy in heart failure

“…[1][2][3] More recently, investigations in the cardiovascular field [4][5][6] have shown associations of cfDNA with cardiovascular risk factors, 7 cardiovascular disease status (acute myocardial infarction and atrial fibrillation), 6 and for the early diagnosis of heart transplant rejection. [8][9][10] However, despite knowing that cell death is one of the features of heart failure (HF) pathobiology, cfDNA has never been investigated in chronic HF. The aim of the present study was to assess, for the first time, the role of the liquid biopsy in HF, investigating cfDNA levels in HF patients and their associations with clinical status, morbidity and mortality.…”