Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study

Abstract

Identification of biomarkers that assess post-transplant risk is needed to improve long-term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)-05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first post-transplant year. The primary endpoint was a composite of death, graft loss/re-transplantation, biopsy proven acute rejection (BPAR) and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti-HLA- and auto-antibodies, angiogenic proteins, peripheral blood allo-reactivity and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p<0.03) and with recipient anti-HLA antibody (p<0.04). Recipient CMV-negativity (regardless of donor status) was associated with BPAR p<0.001), and increases in plasma vascular endothelial growth factor-C (OR 20; 95%CI:1.9–218) combined with decreases in endothelin-1: (OR 0.14; 95%CI:0.02–0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation.

Genetic and Functional Profiling of CD16-Dependent Natural Killer Activation Identifies Patients at Higher Risk of Cardiac Allograft Vasculopathy

“…The current challenge is to identify non-invasive biomarkers that enable the early stratification of patients at risk 2,[5][6][7][8] to tailor individualized therapeutic approaches that prevent HT failure 6,9 .…”

“…In addition to complemento identify non-invasive biomarkers that y enable the early stratification of patients a at t t ri ri r sk sk sk 2, 2, 2 5 5 5-8 -8 -8 t t to o o ailor individualized therapeutic approaches that prevent HT failure 6,9 .…”

Cholesterol efflux capacity of high-density lipoprotein correlates with survival and allograft vasculopathy in cardiac transplant recipients

“…We performed a second, independent study using samples from the Clinical Trials in Organ Transplantation 05 (CTOT05) study 15 to test the hypothesis that decreased pre-transplant CEC is associated with CAV progression (see Figure 1 for flowchart detailing study designs).…”

Comparative analysis of diagnostic significance of biomarkers’ panels in cardiac recipients in the long term period after transplantation

“…том XIX № В последние годы большое число исследований посвящено разработке и анализу диагностической эффективности различных биомаркеров, участвую-щих в патогенезе повреждения трансплантата [3][4][5][6]. Однако сложность их применения на практике обус-лавливается неспецифичностью тестов и наличием большого числа факторов, влияющих на уровень этих показателей [7][8][9][10][11][12].…”