Temporal Shift in Set of Biomarkers May Correlate With Clinical Outcomes in HFrEF

HFpEF HFrEF Hospital Trends
HFpEF HFrEF Hospital Trends
Clinical outcomes of patients with heart failure were found to correlate with alterations in the levels of a set of biomarkers.

Clinical outcomes of patients with heart failure (HF) were found to correlate with alterations in the levels of a set of biomarkers, according to a prospective cohort study published in the Canadian Journal of Cardiology.

A total of 250 patients (mean age, 68 years; interquartile range [IQR], 58-76 years; 74% men) with HF with reduced ejection fraction (HFrEF; mean duration, 4.7 years; IQR, 1.7-9.8 years) were enrolled at 2 medical centers between 2011 and 2013. Clinical evaluation of HFrEF progression and measurements of 17 cytokines and cytokine receptors from blood samples were conducted at baseline and every 3 months until 2015.

After a median follow-up time of 2.2 years (IQR, 1.4-2.5 years), 53 patients were hospitalized for HF, 3 underwent a heart transplant, 2 had a left ventricular assist device implantation, and 8 died due to cardiovascular complications.

At baseline, the patients with vs without worsening HFrEF symptoms or death differed significantly in age (P =.042), systolic blood pressure (P =.021), HF duration (P <.001), N-terminal pro B-type natriuretic peptide level (P <.001), high sensitivity troponin T level (P <.001), rate of diabetes mellitus (P =.007), rate of atrial fibrillation (P =.030), and use of diuretics (P =.043).

At 24 months prior to worsening symptoms or death, patients with complications had elevated levels of C-C motif chemokine (CCL)-15, tumor necrosis factor (TNF)-R1, and TNF receptor superfamily (TNFRSF)12. As the occurrence of complication approached, divergences in the levels of CCL-16, C-X-C motif chemokine ligand (CXCL)-16, interleukin (IL)-1RT1, IL-1RT2, IL-17RA, IL18BP, IL2-RA, lymphotoxin-b receptor (LTBR), TNF-R2, and TNFSF13B were observed.

All significant correlations with cardiovascular complications were in the positive direction except for TNFRSF6 and IL-6RA.

After adjusting for other cofactors, the strongest correlation between a cardiovascular complication and deviations in biomarker levels were observed for IL-1RT1 (hazard ratio [HR], 3.04; 95% CI, 1.95-5.39), TNFSF13B (HR, 3.01; 95% CI, 1.12-4.48), and TNF-R1 (HR, 2.12; 95% CI, 1.55-2.92).

Study limitations include the fact that biomarkers were measured in a subset of vs all plasma samples, which were deemed by investigators to be the most informative.

“We demonstrate that temporal patterns of several cytokines and cytokine receptors are independently associated with clinical adverse events in patients with stable HF,” concluded the study authors. “These results suggest that repeated measurements of these biomarkers, in addition to traditional cardiac biomarkers, may contribute to personalized risk assessment and herewith better identify high-risk patients.”


Bouwens E, Schuurman A-S, Akkerhuis M, et al. Serially measured cytokines and cytokine receptors in relation to clinical outcome in patients with stable heart failure Serially measured cytokines in heart failure. Can J Cardiol. 2020;S0828-282X(20)30918-1. doi:10.1016/j.cjca.2020.08.010