Statistical performance of 16 posttransplant risk scores in a contemporary cohort of heart transplant recipients
Accurate risk stratification of early heart transplant failure is required to avoid futile transplants and rationalize donor selection. We aimed to evaluate the statistical performance of existing risk scores on a contemporary cohort of heart transplant recipients.
After an exhaustive search, we identified 16 relevant risk scores. From the UNOS database, we selected all first noncombined adult heart transplants performed between 2014 and 2017 for validation. The primary endpoint was death or retransplant during the first year posttransplant.
For all scores, we analyzed their association with outcomes, sensitivity, specificity, likelihood ratios, and discrimination (concordance index and overlap of individual scores). The cohort included 9396 patients. All scores were significantly associated with the primary outcome (P < .001 for all scores). Their likelihood ratios, both negative and positive, were poor. The discriminative performance of all scores was limited, with concordance index ranging from 0.544 to 0.646 (median 0.594) and an important overlap of individual scores between patients with or without the primary endpoint. Subgroup analyses revealed important variation in discrimination according to donor age, recipient age, and the type of assist device used at transplant.
Our findings raise concerns about the use of currently available scores in the clinical field.
Identification and characterization of trajectories of cardiac allograft vasculopathy after heart transplantation
One of the most common reasons for long-term graft failure and patient death is an accelerated form of coronary artery disease called cardiac allograft vasculopathy. It is a frequent complication that affects up to half of patients within 10 years following heart transplantation. Yet, until now, little has been known about the different evolutive profiles of cardiac allograft vasculopathy and their risk factors.
Sunday September 24, 2017
1/ MOLECULAR CORRELATES OF ENDOTHELIAL MTOR ACTIVATION IN HEART TRANSPLANT RECIPIENTS
Session: “ Basic and translational immunology” (17:45 to 18:45)
Location: Room 118 + 119 – 18:29
M Racapé, A Loupy, J Reeve, J Venner , R Guillemain, L Hidalgo, C Lefaucher, X Jouven, P Bruneval, J Duaong Van Huyen, P Halloran
The detection of phosphorylated effectors of the mTOR pathway such as phosphorylated-S6RP in endothelial cells by immunohistochemistry (IHC) has been associated with Antibody-Mediated allograft Rejection (AMR). The aim of this study was to evaluate the molecular phenotype related to the endothelial detection of pS6RP in heart transplant recipients.
This case-control study included 41 heart transplant patients from four French referral centers with biopsy proven antibody-mediated rejection (pAMR+) and a matched control group of 30 patients without rejection (pAMR0) based on the updated ISHLT classification. From these patients, 94 endomyocardial biopsies (EMB) had adequate material for microarray analysis and endothelial expression analysis of pS6RP by IHC. We also determined the allograft gene expression profile using the ABMR molecular score in addition to pathogenesis-based transcripts reflecting endothelial activation (DSAST and ENDAT), macrophage burden (QCMAT), gamma-interferon response (GRIT) and NK-cell burden (NKB) (http://atagc.med.ualberta.ca).
Among the 94 EMBs included in the main analyses, 50 were pAMR+ (53.2%) and 44 (46.8%) were pAMR0 normal EMBs. Endothelial expression of pS6RP was observed in 27/50 (54%) of pAMR+ biopsies and 12 out of 44 normal biopsies (27.3%, Fischer's exact: p=0.012). As compared with biopsies without pS6RP labeling, biopsies with pS6RP staining showed increased expression of DSAST (Mann-Whitney: p<0.0001), ENDAT (p=0.0009), QCMAT (p=0.0046), NKB (p=0.0001), GRIT (p=0.0008) and increased ABMR molecular score reflecting AMR injury (p=0.0001).
Endothelial activation of mTOR pathway is associated with AMR and increased expression in transcripts reflecting endothelial activation, macrophage burden, microcirculation and NK burden. Our results suggest the importance of the mTOR pathway activation in AMR injury and the potential interest of using mTOR inhibitors in this setting.
Paris Transplant Group
Our global aim is to accelerate the translation of immunological and gene expression discoveries into the clinical field by filling the gap between basic science and applied biomedical researches.