title: Adrenomedullin: a marker of impaired hemodynamics, organ dysfunction, and poor prognosis in cardiogenic shock.
abstract: BACKGROUND
  The clinical CardShock risk score, including baseline lactate levels, was recently shown to facilitate risk stratification in patients with cardiogenic shock (CS). As based on baseline parameters, however, it may not reflect the change in mortality risk in response to initial therapies. Adrenomedullin is a prognostic biomarker in several cardiovascular diseases and was recently shown to associate with hemodynamic instability in patients with septic shock. The aim of our study was to evaluate the prognostic value and association with hemodynamic parameters of bioactive adrenomedullin (bio-ADM) in patients with CS.
  
  
  METHODS
  CardShock was a prospective, observational, European multinational cohort study of CS. In this sub-analysis, serial plasma bio-ADM and arterial blood lactate measurements were collected from 178 patients during the first 10 days after detection of CS.
  
  
  RESULTS
  Both bio-ADM and lactate were higher in 90-day non-survivors compared to survivors at all time points (P < 0.05 for all). Lactate showed good prognostic value during the initial 24 h (AUC 0.78 at admission and 0.76 at 24 h). Subsequently, lactate returned normal (≤2 mmol/L) in most patients regardless of later outcome with lower prognostic value. By contrast, bio-ADM showed increasing prognostic value from 48 h and beyond (AUC 0.71 at 48 h and 0.80 at 5-10 days). Serial measurements of either bio-ADM or lactate were independent of and provided added value to CardShock risk score (P < 0.001 for both). Ninety-day mortality was more than double higher in patients with high levels of bio-ADM (>55.7 pg/mL) at 48 h compared to those with low bio-ADM levels (49.1 vs. 22.6%, P = 0.001). High levels of bio-ADM were associated with impaired cardiac index, mean arterial pressure, central venous pressure, and systolic pulmonary artery pressure during the study period. Furthermore, high levels of bio-ADM at 48 to 96 h were related to persistently impaired cardiac and end-organ function.
  
  
  CONCLUSIONS
  Bio-ADM is a valuable prognosticator and marker of impaired hemodynamics in CS patients. High levels of bio-ADM may show shock refractoriness and developing end-organ dysfunction and thus help to guide therapeutic approach in patients with CS. Study identifier of CardShock study NCT01374867 at clinicaltrials.gov.
authors.affiliation: INSERM UMR-S942, Paris, France. heli.tolppanen@helsinki.fi.|Heart Center, Päijät-Häme Central Hospital, Lahti, Finland. heli.tolppanen@helsinki.fi.|Heart and Lung Center, Helsinki University and Helsinki University Hospital, Helsinki, Finland. heli.tolppanen@helsinki.fi.
authors.forename: Heli
authors.identifier: http://orcid.org/0000-0002-3364-8554
authors.initials: H
authors.lastname: Tolppanen
authors.affiliation: INSERM UMR-S942, Paris, France.|Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute IIB-SantPau, Universidad Autónoma de Barcelona, Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rivas-Lasarte
authors.affiliation: Heart and Lung Center, Helsinki University and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Johan
authors.initials: J
authors.lastname: Lassus
authors.affiliation: Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute IIB-SantPau, Universidad Autónoma de Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Sans-Roselló
authors.affiliation: Sphingotec GmbH, Hennigsdorf, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hartmann
authors.affiliation: Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Matias
authors.initials: M
authors.lastname: Lindholm
authors.affiliation: INSERM UMR-S942, Paris, France.|Department of Cardiology, University Heart Center, 8091, Zürich, Switzerland.|Department of Cardiology, University Hospital Zürich, 8091, Zürich, Switzerland.
authors.forename: Mattia
authors.initials: M
authors.lastname: Arrigo
authors.affiliation: Department of Emergency Care, Helsinki University and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Tuukka
authors.initials: T
authors.lastname: Tarvasmäki
authors.affiliation: Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Köber
authors.affiliation: Medical Clinic II, University Hospital Schleswig-Holstein, University Heart Center Lübeck, Lübeck, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Thiele
authors.affiliation: Department of Clinical Chemistry, University of Eastern Finland, Kuopio, Finland.|Eastern Finland Laboratory Centre, Kuopio, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Pulkki
authors.affiliation: Department of Internal Medicine and Cardiology, University Hospital Brno, Brno, Czech Republic.|International Clinical Research Centre (ICRC), Brno, Czech Republic.
authors.forename: Jindrich
authors.initials: J
authors.lastname: Spinar
authors.affiliation: Heart Failure Clinic and Secondary Cardiology Department, Attikon University Hospital, Athens, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Parissis
authors.affiliation: Intensive Cardiac Therapy Clinic, Institute of Cardiology, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Banaszewski
authors.affiliation: Department of Cardiology, CINTESIS, Porto Medical School, São João Hospital Center, University of Porto, Porto, Portugal.
authors.forename: Jose
authors.initials: J
authors.lastname: Silva-Cardoso
authors.affiliation: Division of Cardiology, Department of Medical and Surgical Specialties Radiological Sciences and Public Health, University and Civil Hospital of Brescia, Brescia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Carubelli
authors.affiliation: Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute IIB-SantPau, Universidad Autónoma de Barcelona, Barcelona, Spain.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sionis
authors.affiliation: Department of Emergency Care, Helsinki University and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Veli-Pekka
authors.initials: VP
authors.lastname: Harjola
authors.affiliation: INSERM UMR-S942, Paris, France.|Department of Anesthesia and Critical Care, University Hospital Saint Louis Lariboisière, APHP, Paris, France.|University Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mebazaa
keywords: Adrenomedullin; Biomarkers; Cardiogenic shock; Hemodynamics; Lactate; Mortality