Bio-adrenomedullin as a marker of congestion in patients with new-onset and worsening heart failure

Eur J Heart Fail. 2019 Jun;21(6):732-743. doi: 10.1002/ejhf.1437. Epub 2019 Mar 6.


Background: Secretion 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 results: The 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.

Conclusions: Plasma 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.

Keywords: Adrenomedullin; Bio-adrenomedullin; Congestion; Heart failure; Pro-adrenomedullin.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin / blood*
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Cohort Studies
  • Disease Progression
  • Female
  • Heart Failure / blood*
  • Heart Failure / complications*
  • Heart Failure / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Stroke Volume / physiology


  • Biomarkers
  • Adrenomedullin