• Jozine M Ter Maaten, Daan Kremer, Biniyam G Demissei, Joachim Struck, Andreas Bergmann, Stefan D Anker, Leong L Ng, Kenneth Dickstein, Marco Metra, Nilesh J Samani, Simon P R Romaine, John Cleland, Nicolas Girerd, Chim C Lang, Dirk J van Veldhuisen, and Adriaan A Voors.
• Department of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
• Eur. J. Heart Fail. 2019 Jun 1; 21 (6): 732-743.

BackgroundSecretion of adrenomedullin (ADM) is stimulated by volume overload to maintain endothelial barrier function, and higher levels of biologically active (bio-) ADM in heart failure (HF) are a counteracting response to vascular leakage and tissue oedema. This study aimed to establish the value of plasma bio-ADM as a marker of congestion in patients with worsening HF.Methods And ResultsThe association of plasma bio-ADM with clinical markers of congestion, as well as its prognostic value was studied in 2179 patients with new-onset or worsening HF enrolled in BIOSTAT-CHF. Data were validated in a separate cohort of 1703 patients. Patients with higher plasma bio-ADM levels were older, had more severe HF and more signs and symptoms of congestion (all P < 0.001). Amongst 20 biomarkers, bio-ADM was the strongest predictor of a clinical congestion score (r2  = 0.198). In multivariable regression analysis, higher bio-ADM was associated with higher body mass index, more oedema, and higher fibroblast growth factor 23. In hierarchical cluster analysis, bio-ADM clustered with oedema, orthopnoea, rales, hepatomegaly and jugular venous pressure. Higher bio-ADM was independently associated with impaired up-titration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers after 3 months, but not of beta-blockers. Higher bio-ADM levels were independently associated with an increased risk of all-cause mortality and HF hospitalization (hazard ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.002, per log increase). Analyses in the validation cohort yielded comparable findings.ConclusionsPlasma bio-ADM in patients with new-onset and worsening HF is associated with more severe HF and more oedema, orthopnoea, hepatomegaly and jugular venous pressure. We therefore postulate bio-ADM as a congestion marker, which might become useful to guide decongestive therapy.© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.

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