Current guidelines recommend measuring natriuretic peptide biomarkers to establish prognosis in patients with chronic heart failure with reduced ejection fraction (HFrEF). We assessed whether a combination biomarkers approach improve prognostication in stable HFrEF patients.

An observational cohort study recruited 202 stable HFrEF patients at a single center, tertiary care hospital undergoing elective cardiac resynchronization therapy device placement from 2013 to 2015. Twenty-four biomarkers were analyzed individually and in combination using Cox proportion hazard regression model for major adverse cardiac event (MACE) (death, cardiac transplant, LVAD placement) and MACE plus HF hospitalizations.

The single best biomarker for predicting MACE is peripheral mid‐regional pro‐adrenomedullin (MR-proADM) (C statistic=0.771±0.045) compared to current guideline recommended N-terminal pro b-type natriuretic peptide (NT-proBNP) (C=0.668±0.046). The best combined biomarkers for predicting MACE are blood urea nitrogen (BUN), coronary sinus C-reactive protein (CRP), peripheral MR-proANP and peripheral sST2 (C=0.767 ± 0.036).

In this observational cohort, the combined biomarkers (BUN, CRP, MR-proANP and sST2) or the single biomarker (MR-proADM) was superior to NT-proBNP, the current guideline recommended biomarker in predicting cardiovascular outcomes in HFrEF patients. Larger studies are needed to validate these findings and examine whether single or combined biomarkers improve HFrEF prognostication.