Abstract 18472: Plasma Proteome Changes in Heart Failure and Non-Heart Failure Patients Undergoing Cardiac Surgery

Abstract

Introduction: Patients with and without heart failure display different clinical courses after cardiac surgery. Hypothesis: Unbiased analyses of the plasma proteome from extreme phenotypes in myocardial function may identify differences in candidate proteins differentially modified by cardiac surgery using cardiopulmonary bypass (CPB). Methods: We combined two prospectively-collected datasets: Left ventricular assist device (LVAD) recipients from the INSPIRE-FLO trial (N=94, NCT03081052) and coronary artery bypass graft (CABG) surgery patients with normal biventricular function (N=50). For each population, we obtained EDTA-plasma from arterial blood sampling in the operating room and on postoperative day 1. Including quality control pools, 304 total samples were digested in a 96-well format with trypsin. Peptides were analyzed by microflow liquid chromatography coupled to tandem mass spectrometry using data-independent acquisition. Proteins were identified and quantified at a 1% false discovery rate (FDR) in Spectronaut. Statistical analyses utilized a t-test with FDR correction (significance defined by log2FC>1 and q<0.05). Results: There were 943 protein groups quantified in at least one plasma sample. Patients undergoing LVAD surgery had significantly higher levels of 135 proteins including acute phase reactants (CRP, SAA1, SAA2), putative neutrophil-derived proteins (S100A8/9) and markers of renal insufficiency (B2M and REG3A) (Figure 1). Cardiac surgery using cardiopulmonary bypass increased acute phase and inflammatory markers, and cardiac proteins (ENOB, MYG and KCRM), with NGAL, TIMP1 and PAI1 among proteins with higher absolute increase after LVAD implantation versus CABG surgery ( Fig.1 ). Conclusions: Unbiased analyses of the plasma proteome identifies baseline and postoperative differences associated with extreme phenotypes of myocardial function undergoing cardiac surgery using CPB.