Quantifying inflammation using interleukin‐6 for improved phenotyping and risk stratification in acute heart failure

Abstract

AbstractAimsSystemic inflammation may be central in the pathophysiology of acute heart failure (AHF). We aimed to assess the possible role of systemic inflammation in the pathophysiology, phenotyping, and risk stratification of patients with AHF.Methods and resultsUsing a novel Interleukin‐6 immunoassay with unprecedented sensitivity (limit of detection 0.01 ng/L), we quantified systemic inflammation in unselected patients presenting with acute dyspnoea to the emergency department in a multicentre study. One‐year mortality was the primary prognostic endpoint. Among 2042 patients, 1026 (50.2%) had an adjudicated diagnosis of AHF, 83.7% of whom had elevated interleukin‐6 concentrations (>4.45 ng/L). Interleukin‐6 was significantly higher in AHF patients compared to patients with other causes of dyspnoea (11.2 [6.1–26.5] ng/L vs. 9.0 [3.2–32.3] ng/L, p < 0.0005). Elevated interleukin‐6 concentrations were independently predicted by increasing N‐terminal pro‐B‐type natriuretic peptide and high‐sensitivity cardiac troponin T, as well as the clinical diagnosis of infection. Among the different AHF phenotypes, interleukin‐6 concentrations were highest in patients with cardiogenic shock (25.7 [14.0–164.2] ng/L) and lowest in patients with hypertensive AHF (9.3 [4.8–21.6] ng/L, p = 0.001). Inflammation as quantified by interleukin‐6 was a strong and independent predictor of 1‐year mortality both in all AHF patients, as well as those without clinically overt infection at presentation (adjusted hazard ratio [95% confidence interval] 1.45 [1.15–1.83] vs. 1.48 [1.09–2.00]). The addition of interleukin‐6 significantly improved the discrimination of the BIOSTAT‐CHF risk score.ConclusionAn unexpectedly high percentage of patients with AHF have subclinical systemic inflammation as quantified by interleukin‐6, which seems to contribute to AHF phenotype and to the risk of death.