Angiopoietin-2 in acute myocardial infarction complicated by cardiogenic shock--a biomarker substudy of the IABP-SHOCK II-Trial.
OBJECTIVE
Angiopoietin-2 (Ang-2) is a mediator of capillary leakage, and increased Ang-2 levels were associated with poor in-hospital outcome in a pilot study in cardiogenic shock (CS). In this larger study, we followed this hypothesis and aimed at assessing the predictive role of Ang-2 on short- and long-term mortality, investigating the effect of intra-aortic balloon pump (IABP) treatment on Ang-2 levels, and identifying clinical and procedural predictors of increased Ang-2.


RESULTS
In the IABP-SHOCK II-trial, 600 patients with CS complicating acute myocardial infarction were assigned to therapy with or without IABP. This substudy included 189 randomized patients with serial blood sampling performed at days 1, 2, and 3. No significant differences in Ang-2 levels were found between patients with or without IABP. The Ang-2 levels above the median at day 1 were associated with 30-day [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.26-3.10, P = 0.002) and 1-year mortality (HR 2.21, 95% CI 1.49-3.27, P < 0.001). Stratification of patients according to Ang-2 levels at day 3 increased these associations (30 days HR 5.15, 95% CI 2.80-9.45, P < 0.001; 1 year HR 5.24, 95% CI 3.19-8.58, P < 0.001). The Ang-2 concentrations were independent predictors for mortality in multivariate analysis (30 days HR 4.82, 95% CI 1.52-15.23, P = 0.007; 1 year HR 2.01, 95%CI 1.24-3.24, P = 0.005). Predictors of increased Ang-2 levels at day 3 were baseline Ang-2, development of acute kidney injury, bleeding events or transfusion, and impaired reperfusion.


CONCLUSIONS
In CS, high levels of Ang-2 are independently associated with poor short- and long-term outcome and associated with the reperfusion success as well as complications.


BACKGROUND
URL: www.clinicaltrials.gov; unique identifier: NCT00491036.
Medical Clinic II/Cardiology/Angiology/Intensive Care Medicine, University Heart Centre Lübeck, University Hospital Schleswig-Holstein (UKSH), Ratzeburger Allee 160, 23538, Lübeck, Germany.
Janine
J
Pöss
Medical Clinic II/Cardiology/Angiology/Intensive Care Medicine, University Heart Centre Lübeck, University Hospital Schleswig-Holstein (UKSH), Ratzeburger Allee 160, 23538, Lübeck, Germany.|Clinic for Internal Medicine/Cardiology, University of Leipzig - Heart Centre, Leipzig, Germany.
Georg
G
Fuernau
Clinic for Internal Medicine/Cardiology, University of Leipzig - Heart Centre, Leipzig, Germany.
Daniel
D
Denks
Medical Clinic II/Cardiology/Angiology/Intensive Care Medicine, University Heart Centre Lübeck, University Hospital Schleswig-Holstein (UKSH), Ratzeburger Allee 160, 23538, Lübeck, Germany.|Clinic for Internal Medicine/Cardiology, University of Leipzig - Heart Centre, Leipzig, Germany.
Steffen
S
Desch
Medical Clinic II/Cardiology/Angiology/Intensive Care Medicine, University Heart Centre Lübeck, University Hospital Schleswig-Holstein (UKSH), Ratzeburger Allee 160, 23538, Lübeck, Germany.|Clinic for Internal Medicine/Cardiology, University of Leipzig - Heart Centre, Leipzig, Germany.
Ingo
I
Eitel
Clinic for Internal Medicine/Cardiology, University of Leipzig - Heart Centre, Leipzig, Germany.|Herzzentrum, Segeberger Kliniken GmbH, Bad Segeberg, Germany.
Suzanne
S
de Waha
Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
Andreas
A
Link
Clinic for Internal Medicine/Cardiology, University of Leipzig - Heart Centre, Leipzig, Germany.
Gerhard
G
Schuler
Clinic for Internal Medicine/Cardiology, University of Leipzig - Heart Centre, Leipzig, Germany.
Volker
V
Adams
Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
Michael
M
Böhm
Medical Clinic II/Cardiology/Angiology/Intensive Care Medicine, University Heart Centre Lübeck, University Hospital Schleswig-Holstein (UKSH), Ratzeburger Allee 160, 23538, Lübeck, Germany.|Clinic for Internal Medicine/Cardiology, University of Leipzig - Heart Centre, Leipzig, Germany.
Holger
H
Thiele
D000368:Aged; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007423:Intra-Aortic Balloon Pumping / Q000009:adverse effects / Q000379:methods; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000401:mortality; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D012770:Shock, Cardiogenic / Q000097:blood / Q000209:etiology; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome
D042702:Angiopoietin-2; D015415:Biomarkers
Acute myocardial infarction; Angiopoietin-2; Assist device; Cardiogenic shock; Outcome