Abstract 17527: Plasma Proteomic Representations of Central Hemodynamics Over Time in Heart Failure

Abstract

Introduction: Perturbation of central hemodynamic parameters are defining features in heart failure (HF) and strong prognostic factors, including increased filling pressures, reduced cardiac output (CI), extended blood circulation times and increased peripheral oxygen extraction (ΔAVO2). Invasive catheterization is used for precise assessment of central hemodynamics. Hypothesis: We postulated that plasma proteins may serve as non-invasive representations of central hemodynamics in HF patients. Methods: Affinity-based plasma proteomic profiling of 1305 proteins was applied to a cohort of patients with advanced HF undergoing invasive cardiac catheterization before and 6 months after heart transplantation. A total of 30 central hemodynamic parameters were measured and calculated. Protein profiles associated with central hemodynamics over time were identified from repeated-measures models. Results: We identified 1304 associations for 201 unique proteins meeting our Bonferroni-adjusted significance threshold (p<1x10-6) for at least one hemodynamic parameter. Most of the 201 proteins were associated with more than one parameter. Most proteins (70%) associated with parameters in more than one of five domains (filling pressures, left ventricular (LV) function, right ventricular (RV) function, systemic arterial function, pulmonary arterial function). No proteins were associated with 6 of the 30 hemodynamic parameters, which changed little after transplantation and related to arterial function or RV function. The largest number of protein associations were observed for RAP, cardiac power index, left ventricular stroke work index, and ΔAVO2 followed by systolic blood pressure, CI, and PAWP (>80). These include expected associations of natriuretic peptides, ST2 with LV function, filling pressures and of angiotensinogen with vascular function parameters. We further describe the discriminatory ability of identified proteins for clinically relevant differences in key hemodynamic parameters. Conclusions: We have identified circulating biomarkers to non-invasively monitor central hemodynamics in HF over time. Our findings may also inform understanding of pathways involved in HF pathophysiology and circulatory regulation.