TY - JOUR
T1 - Sympathetic activation and outcomes in chronic heart failure
T2 - Does the neurohormonal hypothesis apply to mid-range and preserved ejection fraction patients?
AU - Jimenez-Marrero, Santiago
AU - Moliner, Pedro
AU - Rodríguez-Costoya, Iris
AU - Enjuanes, Cristina
AU - Alcoberro, Lidia
AU - Yun, Sergi
AU - Gonzalez-Costello, Jose
AU - Garay, Alberto
AU - Tajes, Marta
AU - Calero, Esther
AU - Hidalgo, Encarnación
AU - Guerrero, Carmen
AU - García-Romero, Elena
AU - Díez-López, Carles
AU - Cainzos-Achirica, Miguel
AU - Comin-Colet, Josep
N1 - Publisher Copyright:
© 2020 European Federation of Internal Medicine
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - Background: Sympathetic 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 Results: SA 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]). Conclusions: Adjusted 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.
AB - Background: Sympathetic 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 Results: SA 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]). Conclusions: Adjusted 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.
KW - Chronic heart failure
KW - Mid-range ejection fraction
KW - Norepinephrine
KW - Outcomes
KW - Preserved ejection fraction
KW - Sympathetic activity
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U2 - 10.1016/j.ejim.2020.07.008
DO - 10.1016/j.ejim.2020.07.008
M3 - Article
C2 - 32718877
AN - SCOPUS:85088813116
SN - 0953-6205
VL - 81
SP - 60
EP - 66
JO - European Journal of Internal Medicine
JF - European Journal of Internal Medicine
ER -