Highlights
- •Information about sympathetic activation (SA) in HFpEF and HFmrEF and its clinical implications is scarce.
- •HFpEF and HFmrEF are associated with lower SA compared to HFrEF in adjusted analyses.
- •SA estimated with NE levels is associated with all-cause and CV mortality across the entire LVEF spectrum.
- •The strongest association between NE and CV mortality is HFmrEF patients, and the weakest in HFpEF.
- •This fact could help to explain why the response to the neurohormonal treatment of patients with HFmrEF is similar to HFrEF, instead of to HFpEF.
Abstract
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.
Keywords
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Article info
Publication history
Published online: July 25, 2020
Accepted:
July 7,
2020
Received in revised form:
June 28,
2020
Received:
May 6,
2020
Identification
Copyright
© 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
