Proteomic Signatures of Heart Failure in Relation to Left Ventricular Ejection Fraction

Background: There is a growing recognition of the inherent limitations of the use of the left ventricular ejection fraction (LVEF) to accurately phenotype patients with heart failure (HF). Objectives: To identify unique proteomic signatures for patients with HFrEF, HFmrEF and HFpEF, as well as to identify molecular differences between ischemic and non-ischemic HF patients. Methods: We used high content aptamer-based proteomics technology (SOMAscan) to interrogate the blood proteome of age and gender matched HF patients within different LVEF groups. Results: Within the Washington University Heart Failure registry, we identified age/sex matched patients within three LVEF categories: HFrEF (LVEF < 40%), HF with a mid-range LVEF (HFmrEF [LVEF 40–50%]) and HF with a preserved LVEF (HFpEF [LVEF > 50%]). We found that patients with HFrEF, HFmrEF, and HFpEF had unique variations in circulating proteins which reflected distinct biological pathophysiologies. Bioinformatics analysis revealed that there were biological themes that were unique to HFrEF, HFpEF and HFmrEF patients. Comparative analyses of patients with HFmrEF with improved LVEF and patients with HFmrEF with unchanged LVEF revealed marked differences between these two patient populations and indicated that patients with recovered LVEF are more similar to patients with HFpEF than to patients with HFrEF. Moreover, there were marked difference in the proteomic signatures of patients with ischemic and non-ischemic HF. Conclusions: Viewed together these findings suggest that it may be possible to use high-content multiplexed proteomics assays in combination with the clinical assessment of LVEF to more accurately identify clinical phenotypes of HF patients.