Abstract
Introduction: Heart failure with preserved ejection fraction (HFpEF) is a poorly understood entity with phenotypic differences to heart failure with reduced ejection fraction (HFrEF). To shed light on the potential pathophysiological difference between HFrEF and HFpEF, multiplex screening of plasma proteins was performed. Methods: From the ARISTOTLE trial with atrial fibrillation (AF) patients, 562 patients with HFrEF and 562 with HFpEF at randomisation were included. Heart failure status at baseline was defined according to systolic left ventricular function; for HFrEF ≤40% and for HFpEF >40%. Plasma samples were analysed with conventional immunoassays and OLINK proximity extension assay panels; CVDII, CVDIII and the inflammation panel. Associations between biomarkers and HF subtype was evaluated with Wilcoxon–Mann–Whitney test with Bonferroni-Holm adjustment for multiplicity. Results: Out of 269 biomarkers, 53 biomarkers differed between the HF subtypes. After adjustment for multiplicity, nine biomarkers had the strongest associations with difference between HFrEF and HFpEF (Figure). In HFrEF, the proteins levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP), cardiac troponin-T (cTnT-hs), renin, growth differentiation factor-15 (GDF-15), angiotensin-converting enzyme 2 (ACE-2) and interleukin-6 (IL-6) were higher than in HFpEF, whereas levels of stem cell factor (SCF) and leptin were higher (Figure) in HFpEF. Conclusions: HFrEF was more strongly associated with elevated markers of cardiorenal dysfunction, the renin-angiotensin-aldosterone system and oxidative stress/inflammation while HFpEF was more strongly associated with higher levels of adipose tissue metabolism and vasculogenesis and tissue repair proteins. These findings add valuable knowledge to the understanding of the underlying differing biological mechanisms in the HF subtypes HFrEF and HFpEF in an AF population.
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