Gene Expression Profiling Test (GEP) Scores and Outcomes of Heart Transplant with Prior Mechanical Circulatory Support: Results from IMAGE and CARGO II

A GEP test has been established as a non-invasive surveillance method to rule out acute cellular rejection. The GEP score is computed from the expression levels of 11 informative genes which are associated with immune activation. We hypothesize that prior mechanical circulatory support (MCS) of heart transplant recipient is associated with carry-over effects on the recipient’s immune system that may be detected by changes in GEP. GEP scores (AlloMap) and associated clinical information about prior MCS from heart transplant recipients from the IMAGE and CARGO II studies were analyzed. For each patient in the MCS or no prior MCS groups, the patient’s average AlloMap score and 11 gene subcomponents were computed, overall and within time periods: 2 - 6 m, 7 - 12 m, 13 - 24 m, 25 - 36 m, and ≥ 37 m post transplant. The mean GEP score and gene subcomponent levels for MCS and no prior MCS groups were compared by t test. The clinical outcomes (hemodynamic compromise or death) in patients with and without prior MCS were not different in these studies. Although no overall effect of prior MCS was observed on the total AlloMap score in the IMAGE or CARGO II studies; three genes (WDR40A, G6b, PF4) were significantly decreased in MCS vs no prior MCS patients in both CARGO II and IMAGE (only in the 2 -6 or 7-12 m time frames, respectively (Table 1) with a mean reduction of up to 40% in the absolute value. Compared to controls, prior MCS may be associated with early decreased expression of 3 gene subcomponents associated with hematopoesis or platelet activation in the AlloMap GEP signature (in the first 12 months). The clinical relevance of these differences requires further investigation and may add to our understanding of the effects of MCS on the hematological system.Tabled 1