Combination Biomarkers for Risk Stratification in Patients With Chronic Heart Failure Biomarkers Prognostication in HF

Background: 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 patients with stable HFrEF.

Methods and results: An observational cohort study recruited 202 patients with stable HFrEF 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 events (ie, death, cardiac transplant, left ventricular assist device placement), and major adverse cardiac events plus HF hospitalizations. The single best biomarker for predicting major adverse cardiac events is peripheral mid-regional pro-adrenomedullin (C statistic = 0.771 ± 0.045) compared to current guideline recommended N-terminal pro b-type natriuretic peptide (C=0.668 ± 0.046). The best combined biomarkers for predicting major adverse cardiac events are blood urea nitrogen, coronary sinus C-reactive protein, peripheral mid-regional pro-atrial natriuretic peptide and peripheral soluble IL-1 receptor-like 1 (C = 0.767 ± 0.036).

Conclusions: In this observational cohort, the combined biomarkers (blood urea nitrogen, C-reactive protein, mid-regional pro-atrial natriuretic peptide and soluble IL-1 receptor-like 1) or the single biomarker (mid-regional pro-adrenomedullin) was superior to N-terminal pro B-type natriuretic peptide, the current guideline recommended biomarker in predicting cardiovascular outcomes in patients with HFrEF. Larger studies are needed to validate these findings and examine whether single or combined biomarkers improve HFrEF prognostication.