The novel cystatin C, lactate, interleukin-6, and N-terminal pro-B-type natriuretic peptide (CLIP)-based mortality risk score in cardiogenic shock after acute myocardial infarction

Author:

Ceglarek Uta1,Schellong Paul1ORCID,Rosolowski Maciej1ORCID,Scholz Markus2ORCID,Willenberg Anja1,Kratzsch Jürgen1,Zeymer Uwe3,Fuernau Georg4ORCID,de Waha-Thiele Suzanne45,Büttner Petra6,Jobs Alexander56,Freund Anne6,Desch Steffen56,Feistritzer Hans-Josef6,Isermann Berend1ORCID,Thiery Joachim1ORCID,Pöss Janine6,Thiele Holger6ORCID

Affiliation:

1. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital, P.-List-Str. 13, 04103 Leipzig, Germany

2. Institute of Medical Informatics, Statistics and Epidemiology, University Leipzig, Germany

3. Klinikum Ludwigshafen und Institut für Herzinfarktforschung, Ludwigshafen, Germany

4. University Heart Center Lübeck, Lübeck, Germany

5. German Center for Cardiovascular Research (DZHK), Lübeck, Germany

6. Heart Center Leipzig at University of Leipzig, Department of Internal Medicine/Cardiology, Strümpellstr.. 39, 04289 Leipzig, and Leipzig Heart Institute, Leipzig, Germany

Abstract

Abstract Background  Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) still reaches excessively high mortality rates. This analysis is aimed to develop a new easily applicable biomarker-based risk score. Methods and results  A biomarker-based risk score for 30-day mortality was developed from 458 patients with CS complicating AMI included in the randomized CULPRIT-SHOCK trial. The selection of relevant predictors and the coefficient estimation for the prognostic model were performed by a penalized multivariate logistic regression analysis. Validation was performed internally, internally externally as well as externally in 163 patients with CS included in the randomized IABP-SHOCK II trial. Blood samples were obtained at randomization. The two trials are registered with ClinicalTrials.gov (NCT01927549 and NCT00491036), are closed to new participants, and follow-up is completed. Out of 58 candidate variables, the four strongest predictors for 30-day mortality were included in the CLIP score (cystatin C, lactate, interleukin-6, and N-terminal pro-B-type natriuretic peptide). The score was well calibrated and yielded high c-statistics of 0.82 [95% confidence interval (CI) 0.78–0.86] in internal validation, 0.82 (95% CI 0.75–0.89) in internal-external (temporal) validation, and 0.73 (95% CI 0.65–0.81) in external validation. Notably, it outperformed the Simplified Acute Physiology Score II and IABP-SHOCK II risk score in prognostication (0.83 vs 0.62; P < 0.001 and 0.83 vs. 0.76; P = 0.03, respectively). Conclusions  A biomarker-only score for 30-day mortality risk stratification in infarct-related CS was developed, extensively validated and calibrated in a prospective cohort of contemporary patients with CS after AMI. The CLIP score outperformed other clinical scores and may be useful as an early decision tool in CS.

Funder

European Union, 7th Framework Programme

German Heart Research Foundation, German Cardiac Society

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine

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