Please use this identifier to cite or link to this item: https://doi.org/10.1002/ehf2.12615
Title: Circulating neuregulin1-? in heart failure with preserved and reduced left ventricular ejection fraction
Authors: Hage, C.
Wärdell, E.
Linde, C.
Donal, E.
Lam, C.S.P. 
Daubert, C.
Lund, L.H.
Månsson-Broberg, A.
Keywords: Coronary artery disease
HFpEF
HFrEF
Neuregulin1-?
Prognosis
Issue Date: 2020
Publisher: Wiley-Blackwell
Citation: Hage, C., Wärdell, E., Linde, C., Donal, E., Lam, C.S.P., Daubert, C., Lund, L.H., Månsson-Broberg, A. (2020). Circulating neuregulin1-? in heart failure with preserved and reduced left ventricular ejection fraction. ESC Heart Failure 7 (2) : 445-455. ScholarBank@NUS Repository. https://doi.org/10.1002/ehf2.12615
Rights: Attribution-NonCommercial 4.0 International
Abstract: Aims: Neuregulin1-? (NRG1-?) is released from microvascular endothelial cells in response to inflammation with compensatory cardioprotective effects. Circulating NRG1-? is elevated in heart failure (HF) with reduced ejection fraction (HFrEF) but not studied in HF with preserved EF (HFpEF). Methods and results: Circulating NRG1-? was quantified in 86 stable patients with HFpEF (EF ?45% and N-terminal pro-brain natriuretic peptide >300 ng/L), in 86 patients with HFrEF prior to and after left ventricular assist device (LVAD) and/or heart transplantation (HTx) and in 21 healthy controls. Association between NRG1-? and the composite outcome of all-cause mortality/HF hospitalization in HFpEF and all-cause mortality/HTx/LVAD implantation in HFrEF with and without ischaemia assessed as macrovascular coronary artery disease was assessed. In HFpEF, median (25th–75th percentile) NRG1-? was 6.5 (2.1–11.3) ng/mL; in HFrEF, 3.6 (2.1–7.6) ng/mL (P = 0.035); after LVAD, 1.7 (0.9–3.6) ng/mL; after HTx 2.1 (1.4–3.6) ng/mL (overall P < 0.001); and in controls, 29.0 (23.1–34.3) ng/mL (P = 0.001). In HFrEF, higher NRG1-? was associated with worse outcomes (hazard ratio per log increase 1.45, 95% confidence interval 1.04–2.03, P = 0.029), regardless of ischaemia. In HFpEF, the association of NRG1-? with outcomes was modified by ischaemia (log-rank P = 0.020; Pinteraction = 0.553) such that only in ischaemic patients, higher NRG1-? was related to worse outcomes. In contrast, in patients without ischaemia, higher NRG1-? trended towards better outcomes (hazard ratio 0.71, 95% confidence interval 0.48–1.05, P = 0.085). Conclusions: Neuregulin1-? was reduced in HFpEF and further reduced in HFrEF. The opposing relationships of NRG1-? with outcomes in non-ischaemic HFpEF compared with HFrEF and ischaemic HFpEF may indicate compensatory increases of cardioprotective NRG1-? from microvascular endothelial dysfunction in the former (non-ischaemic HFpEF), but this compensatory mechanism is overwhelmed by the presence of ischaemia in the latter (HFrEF and ischaemic HFpEF). © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
Source Title: ESC Heart Failure
URI: https://scholarbank.nus.edu.sg/handle/10635/196181
ISSN: 2055-5822
DOI: 10.1002/ehf2.12615
Rights: Attribution-NonCommercial 4.0 International
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