CS as a Novel Biomarker for Diagnosis of Cardiac Allograft Rejection

Abstract

Purpose Cardiac bridging integrator 1 (cBIN1) is a cardiomyocyte protein which regulates excitation-contraction coupling and is downregulated with adverse myocardial remodeling. The natural log of the inverse of cBIN1 plasma concentration known as CS, has been shown to be a diagnostic and prognostic marker for ambulatory heart failure patients. In this pilot study, we examined the performance of CS as a diagnostic marker of cardiac allograft rejection. Methods Out of 708 heart transplant (HT) recipients consented for the study from 2014 to 2018, 12 patients experienced advanced rejection (AMR/ACR grade ≥2) with CS level drawn at the time. Convalescent sera were drawn at least 6 months post therapy. A control group of 11 patients was matched by age, sex and time since HT. CS was measured in plasma samples by Sarcotein, Inc. Pair-wise comparison of CS among the 2 groups was performed using the Wilcoxon signed rank test. Major adverse outcomes (MACE), defined as ventricular tachycardia, cardiac allograft vasculopathy, recurrent rejection, cardiac hospitalization, and death were determined by chart review at most recent clinic visit. Results Rejection occurred at 211 (IQR 127-303) days post-HT. Patients with rejection had significantly lower CS levels compared to controls (1.92[IQR 1.57-2.33] vs 2.36[IQR 1.86-3.71] p=0.03). Following anti-rejection therapy, CS values were determined at 189 (IQR 126.8-303) days after the episode and did not differ significantly from the time of rejection. Notably, post rejection patients experienced a high rate of MACE (7/12) at 4 years of follow-up. Those who experienced MACE had a numerically higher median increase in CS values on follow-up compared to those who did not (1.04 vs 0.50). Conclusion In this pilot study, CS shows promise as a marker of cardiac allograft rejection. CS was significantly decreased by 20% in the setting of rejection compared to matched control samples. Larger studies are needed to validate our findings and determine the prognostic value of CS level changes post-therapy.