Abstract 2426: Relationship Between Invasive Hemodynamics And Peripheral Blood Mononuclear Cell Gene Expression After Heart Transplantation In The Absence Of Moderate Or Severe Acute Cellular Rejection
Background: An 11 gene peripheral blood Mononuclear Cell (PBMC) Gene Expression Profiling test (GEP) was recently introduced into clinical practice to identify heart transplant (HTx) patients under low risk of moderate-severe acute cellular cardiac allograft rejection.
Hypothesis: A molecular test to monitor the allograft related immune response provides information about allograft performance as measured by invasive hemodynamics.
Methods: Independent data from patients undergoing GEP monitoring at the time of routine endomyocardial biopsy (EMB) and hemodynamic evaluation were retrospectively analyzed. GEP test scores (range 0 – 40) and normalized RT-PCR cycle thresholds (CT) of each individual gene were correlated with hemodynamic variables. Statistical comparisons were done with univariate and multivariate analysis. A p-value <0.05 was considered significant.
Results: independent samples from 62 patients aged 42.5 years ± 19.9 (chosen as the closest to year one post HTx) were selected for this analysis if they had GEP score, EMB and right heart catheterization at the time of the clinical encounter. All EMB were ISHLT grade 0R (64.5%) and 1R (35.5%). Average GEP score was 29.9±5.3. GEP score was significantly related to mixed venous oxygen saturation % (MVO2Sat%) (r=0.25, p=0.02). Out of the 11 genes included in the GEP score MIR (r=0.32, p=0.01), WDR40A (r=0.39, p=0.001), RHOU (r=0.34, p=0.006) correlated with MVO2Sat% and MIR (−0.28, p=0.028), WDR40A (−0.35, p=0.005) and ITGA4 (r=0.40, p=0.0015) with right atrial pressure (RAP). Multivariate modeling, controlled for possible confounders including age, time post HTx, serum creatinine and prednisone dose showed WDRA40 (B=2.12, p=0.02) and RHOU (B=3.96, p=0.01) independently related to MVO2Sat% and ITGA4 (B=4.9, p=0.01) and WDR40A (B=−1.52, p=0.02) as independent predictors of RAP.
Conclusions: Gene expression profiling of PBMC may provide information about the underlying graft physiology either in the absence of moderate of severe cellular rejection. Among the 11 GEP genes WDRA40, RHOU and ITGA4 are independently related to hemodynamic variables and need to be further evaluated as surrogates of allograft function.