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 The authors sought to identify unique proteomic signatures for patients with HF with reduced ejection fraction (HFrEF), HF with a midrange LVEF (HFmrEF), and HF with preserved ejection fraction (HFpEF), as well as to identify molecular differences between patients with ischemic and nonischemic HF. METHODS We used high-content aptamer-based proteomics technology (SOMAscan) to interrogate the blood proteome of age- and sex-matched patients with HF within different LVEF groups. RESULTS Within the Washington University Heart Failure Registry, we identified age/sex-matched patients within 3 LVEF categories: HFrEF (LVEF <40%), HFmrEF (LVEF 40% to 50%), and HFpEF (LVEF >50%). We found that patients with HFrEF, HFmrEF, and HFpEF had unique variations in circulating proteins that reflected distinct biological pathophysiologies. Bioinformatics analysis revealed that there were biological themes that were unique to patients with HFrEF, HFpEF, or HFmrEF. Comparative analyses of patients with HFmrEF with improved LVEF and patients with HFmrEF with unchanged LVEF revealed marked differences between these 2 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 differences in the proteomic signatures of patients with ischemic and nonischemic 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 patients with HF. Published by Elsevier on behalf of the American College of Cardiology Foundation.