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.

Department of Cardiology CINTESIS Porto Medical School São João Hospital Center University of Porto Porto Portugal

Department of Cardiology Rigshospitalet University of Copenhagen Copenhagen Denmark

Department of Clinical Chemistry University of Eastern Finland Kuopio Finland Eastern Finland Laboratory Centre Kuopio Finland

Department of Emergency Care Helsinki University and Helsinki University Hospital Helsinki Finland

Department of Internal Medicine and Cardiology University Hospital Brno Brno Czech Republic International Clinical Research Centre Brno Czech Republic

Division of Cardiology Department of Medical and Surgical Specialties Radiological Sciences and Public Health University and Civil Hospital of Brescia Brescia Italy

Heart and Lung Center Helsinki University and Helsinki University Hospital Helsinki Finland

Heart Failure Clinic and Secondary Cardiology Department Attikon University Hospital Athens Greece

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

INSERM UMR S942 Paris France Department of Cardiology University Heart Center 8091 Zürich Switzerland Department of Cardiology University Hospital Zürich 8091 Zürich Switzerland

INSERM UMR S942 Paris France Heart Center Päijät Häme Central Hospital Lahti Finland Heart and Lung Center Helsinki University and Helsinki University Hospital Helsinki Finland

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

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

Intensive Cardiac Therapy Clinic Institute of Cardiology Warsaw Poland

Medical Clinic 2 University Hospital Schleswig Holstein University Heart Center Lübeck Lübeck Germany

Sphingotec GmbH Hennigsdorf Germany

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