Sympathetic and renin-angiotensin-aldosterone system activation in heart failure with preserved, mid-range and reduced ejection fraction

Abstract Background Evidence of sympathetic and renin-angiotensin- aldosteronesystem activation provided a rationale for neurohormonalantagonism in heart failure with reduced ejection fraction (HFrEF), while no data are available in patients with milder degree of systolic dysfunction. We aimed to investigate neurohormonalfunction in HF with preserved and mid-rangeEF (HFpEF/HFmrEF). Methods Three cohorts (n = 189/each) of stable HFpEF, HFmrEF and HFrEF patients were selected (median age 70, 67 and 67 years; male 56%, 73% and 74%, respectively). Patients received a baseline clinical assessment including plasma renin activity(PRA), aldosterone, catecholamines, and N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP) assays, and were followed-up for all-cause death. Results Neuroendocrine profile was similar between HFpEF and HFmrEF, while all neurohormonesexcept epinephrine were higher in HFrEF than in HFmrEF (NT-proBNP 2332 ng/L, IQR 995–5666 vs 575 ng/L, 205–1714; PRA 1.7 ng/mL/h, 0.4–5.6 vs 0.6 ng/mL/h, 0.2–2.6; aldosterone153 ng/L, 85–246 vs 113 ng/L, 72–177; norepinephrine 517 ng/L, 343–844 vs 430 ng/L, 259–624; all p  Conclusions Neurohormonalactivation is present only in a subset of patients with HFpEF and HFmrEF, and may hold clinical significance. Neurohormonalantagonism may be useful in selected HFpEF/HFmrEF population.