Baseline C-reactive protein, cystatin C, growth-differentiation factor-15, interleukin-6 (IL-6), N-terminal B-type natriuretic peptide (NT-proBNP), and troponin T levels are useful biomarkers for heart failure (HF) hospitalization and mortality among patients with atrial fibrillation (AF). These findings were published in the American Heart Journal.

The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE; Identifier: NCT00412984) trial was a double blind, double-dummy, multicenter trial. This substudy of ARISTOTLE data evaluated biomarkers for HF hospitalization and all-cause mortality among patients with AF and HF with reduced ejection fraction (HFrEF; n=2048), HF with preserved ejection fraction (HFpEF; n=2520), and no HF (n=7250).

The HFrEF, HFpEF, and no HF cohorts comprised 20.6%, 42.7%, and 35.7% women; were aged median 67.0, 69.0, and 70.0 years; 50.4%, 49.4%, and 50.1% were randomly assigned to receive warfarin; and 89.6%, 85.0%, and 81.5% had permanent or persistent AF, respectively.

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The distribution of the biomarkers was similar for all markers except C-reactive protein, in which for the other markers HFrEF associated with the highest values and no HF the lowest. The distributions for all markers differed significantly between groups (all P <.001).

During a median follow-up of 1.9 years, 546 patients were hospitalized for HF and 819 died. Event rates were higher among the HFrEF cohort and lowest for the no HF cohort. Consistent associations were observed across biomarkers, in which higher levels associated with increased likelihood of HF hospitalization and all-cause mortality.

After fully adjusting for covariates, NT-proBNP (c2, 101.6; P <.0001), troponin T (c2, 36.1; P <.0001), IL-6 (c2, 23.2; P =.0001), and growth-differentiation factor-15 (c2, 20.2; P =.0005) levels were significantly associated with first hospitalization for HF.

There was evidence of an interaction between HF status and troponin T on first hospitalization for HF after adjusting for all covariates (c2, 6.19; P =.0454) and nonlinear relationships were observed between HF status and NT-proBNP (c2, 4.69; P =.0303) and IL-6 (c2, 4.71; P =.0301) after adjustment.

The results of this study may not be generalizable as this patient population was recruited for a clinical trial and all patients had at least 1 risk factor for stroke.

“In anticoagulated patients with AF, biomarkers indicating cardiorenal dysfunction and inflammation improve the identification of patients with AF at risk of developing HF or worsening of already existing HF,” the study authors wrote. “These biomarkers might be useful for targeting additional HF therapies in patients with AF.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Aulin J, Hijazi Z, Lindbäck J, et al, on behalf of the ARISTOTLE Investigators. Biomarkers and heart failure events in patients with atrial fibrillation in the ARISTOTLE trial evaluated by a multi-state model. Am Heart J. Published online May 13, 2022. doi:10.1016/j.ahj.2022.03.009