P976Elevated biomarkers are associated with increased risk of death and heart failure hospitalization in patients with atrial fibrillation: insights from the ARISTOTLE trial

Abstract

Background: Heart failure (HF) is common in patients with atrial fibrillation (AF). The prognostic value of biomarkers in patients with AF to identify those at risk of complications of HF has not been studied in detail, nor the specific prognostic ability of cardiovascular biomarkers in patients with concomitant AF and HF. Purpose: We investigated the associations of biomarkers representing cardiac dysfunction (N‐terminal B‐type natriuretic peptide (NT‐proBNP) and troponin‐Ths), stress and inflammation (growth‐differentiation factor‐15 (GDF‐15), and interleukin 6 (IL‐6)) with HF hospitalization and death in anticoagulated patients with AF in different heart function subgroups. Methods: In the ARISTOTLE trial 18,201 patients with AF and at least one additional risk f,actor for stroke were randomized to apixaban or warfarin. This substudy included all patients with information on history of HF and left ventricular ejection fraction (LVEF) at entry and had biomarkers measured from plasma collected at randomization (n=11,817). NT‐proBNP, troponin‐T‐hs, and GDF‐15 were measured by immunoassays and IL‐6 by ELISA assays. Patients were divided into three subgroups: (I) HF with reduced ejection fraction (HFrEF) (LVEF≤40% with or without HF symptoms, n=2,047), (II) HF with preserved ejection fraction (HFpEF) (symptomatic HF with LVEF>40%, n=2,520), and (III) No HF (n=7,250). Median follow‐up time was 1.9 years. Associations between biomarkers and HF hospitalization or death were analysed by a multi‐state model, accounting for competing risks, in which the transition rates were adjusted for clinical risk factors. Results: The median concentration of each biomarker was highest in patients with HFrEF followed by HFpEF and lowest in those without HF. During follow‐ up, a total of 545 were hospitalized for HF and 819 died. Increasing levels of all biomarkers showed a non‐linear association with both outcomes (all p<0.0001) in all subgroups (HFrEF, HFpEF, and No HF, respectively) (Figure). The biomarkers remained significantly associated with both outcomes in multivariable models adjusting for clinical characteristics and renal function. Independent of biomarker levels, the HF hospitalization and mortality rate were higher in the HFrEF group followed by HFpEF and lastly the No HF group (Figure). This pattern was more pronounced for HF hospitalizations. Conclusions: In anticoagulated patients with AF, irrespective of initial heart function status, higher concentrations of NT‐proBNP, troponin‐T‐hs, GDF‐15, and IL‐6 were associated with higher risk of HF hospitalization and death in patients with and without HF, regardless of reduced or preserved LVEF.