• Santiago Jimenez-Marrero, Pedro Moliner, Iris Rodríguez-Costoya, Cristina Enjuanes, Lidia Alcoberro, Sergi Yun, Jose Gonzalez-Costello, Alberto Garay, Marta Tajes, Esther Calero, Encarnación Hidalgo, Carmen Guerrero, Elena García-Romero, Carles Díez-López, Miguel Cainzos-Achirica, and Josep Comin-Colet.
• Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Cardio-Oncology Unit, Cardiology Department, Bellvitge University Hospital-Catalan Institute of Oncology (ICO), L'Hospital de Llobregat, Barcelona, Spain.
• Eur. J. Intern. Med. 2020 Nov 1; 81: 60-66.

BackgroundSympathetic activity (SA) is increased in patients with heart failure and reduced ejection fraction (HFrEF) and is associated with poor outcomes. However, its clinical implications are less understood in HF with mid-range (HFmrEF) and preserved ejection fraction (HFpEF). We aimed to study SA across left ventricle ejection fraction (LVEF) groups and its association with clinical outcomes.Methods And ResultsSA estimated by norepinephrine (NE) levels was determined in 742 consecutive outpatients with chronic HF: 348 (47%) with HFrEF, 116 (16%) HFmrEF, and 278 (37%) HFpEF. After a mean follow-up of 15 months, 17% died. Adjusted analyses showed that patients with HFpEF and HFmrEF had lower estimated marginal means of NE levels compared to HFrEF (278 and 116 pg/mL, respectively, vs. 348 pg/mL; p-value=0.005). Adjusted Cox regression analyses showed that high norepinephrine levels independently predicted all-cause mortality (ACM) in all 3 groups. The strongest associations between high NE levels and cardiovascular mortality (CVM) were observed in HFmrEF (HR: 4.7 [1.33-16.68]), while the weakest association was in HFpEF (HR: 2.62 [1.08-6.35]).ConclusionsAdjusted analyses showed that HFpEF and HFmrEF were associated with lower SA compared to HFrEF. Nevertheless, increasing NE levels were independently associated with ACM and CVM in all three LVEF groups. The strongest association between high NE levels and CVM was present in HFmrEF patients, while the weakest was seen in HFpEF. These findings could explain why the response to neurohormonal therapies in patients with HFmrEF is similar to that of patients with HFrEF rather than with HFpEF.Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

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