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Early diagnosis of acute myocardial infarction in patients with mild elevations of cardiac troponin

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Abstract

Background

The early diagnosis of acute myocardial infarction (AMI) in patients with mild elevations of high-sensitivity cardiac troponin (hs-cTn) is a challenge. It is unclear whether copeptin, a marker of endogenous stress, or 1h-hs-cTn changes are better suited to address this important unmet clinical need.

Methods

We prospectively enrolled patients presenting with symptoms suggestive of AMI to the emergency department (ED). Two independent cardiologists adjudicated the final diagnosis. Mild hs-cTn elevations were defined as 26.2 ng/L (99th percentile) to 75 ng/L for hs-cTnI, and 14 ng/L (99th percentile) to 50 ng/L (biological-equivalent to 75 ng/L for hs-cTnI) for hs-cTnT.

Results

Among 1356 patients, 80 (6%) had mild hs-cTnI elevations at presentation. Within this group, AMI was the final diagnosis in 39 patients (49%). The diagnostic accuracy for the diagnosis of AMI as quantified by the area under the receiver operating characteristic curve (AUC) was 0.51 (95% CI 0.39–0.64) for hs-cTnI at presentation, 0.58 (95% CI 0.45–0.71) for copeptin at presentation, and 0.78 (95% CI 0.68–0.88) for 1h-hs-cTnI changes, which was significantly higher as compared to copeptin (p = 0.02) or hs-cTnI alone (p < 0.001). The additional use of 1h-hs-cTnI changes, but not of copeptin, improved diagnostic accuracy of hs-cTnI at presentation (AUC 0.80, 95% CI 0.70–0.90; p = 0.002 for comparison). Similar findings regarding copeptin and 1h-hs-cTnT/I changes were obtained for mild hs-cTnT elevations.

Conclusions

About 6–22% of patients presenting with suggestive AMI to the ED have mild hs-cTnT/I elevations at presentation. In contrast to copeptin, the addition of 1h-hs-cTn changes substantially improves the early diagnosis of AMI.

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Acknowledgements

We are indebted to the patients who participated in the study and to the emergency department staff as well as the laboratory technicians of all participating sites for their most valuable efforts. In addition, we wish to thank Claudia Stelzig, MS, Kathrin Meissner, RN, Michael Freese, RN, Melanie Wieland, RN, Irina Klimmeck, RN, Fausta Chiaverio, RN (all University Hospital Basel, Switzerland), Esther Garrido, MD, Isabel Campodarve, MD, Joachim Gea, MD (Hospital del Mar, IMIM, Barcelona, Spain), Helena Mañé Cruz, NR Carolina Isabel Fuenzalida Inostroza, NR (Hospital Clinic, Barcelona, Spain), and Miguel Angel García Briñón, NR (Hospital Clínico San Carlos, Madrid, Spain). The study was supported by research grants from the Swiss National Science Foundation, the European Union, the Swiss Heart Foundation, Abbott, Beckman Coulter, BRAHMS, Roche, Siemens, 8sense, Nanosphere, Alere and the Department of Internal Medicine, University Hospital Basel.

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    Authors and Affiliations

    1. Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Petersgraben 4, 4031, Basel, Switzerland

      Jasper Boeddinghaus, Tobias Reichlin, Thomas Nestelberger, Raphael Twerenbold, Yvette Meili, Karin Wildi, Petra Hillinger, Maria Rubini Giménez, Janosch Cupa, Lukas Schumacher, Marie Schubera, Patrick Badertscher, Sydney Corbière, Karin Grimm, Christian Puelacher, Zaid Sabti, Dayana Flores Widmer, Nicolas Schaerli, Nikola Kozhuharov, Samyut Shrestha, Tobias Bürge, Patrick Mächler, Michael Büchi, Jens Lohrmann, Stefan Osswald & Christian Mueller

    2. Department of Internal Medicine, University Hospital Basel, University of Basel, Basel, Switzerland

      Jasper Boeddinghaus, Thomas Nestelberger, Petra Hillinger, Maria Rubini Giménez, Karin Grimm & Nicolas Schaerli

    3. GREAT Network, Basel, Switzerland

      Jasper Boeddinghaus, Tobias Reichlin, Thomas Nestelberger, Raphael Twerenbold, Yvette Meili, Karin Wildi, Petra Hillinger, Maria Rubini Giménez, Janosch Cupa, Lukas Schumacher, Marie Schubera, Patrick Badertscher, Sydney Corbière, Karin Grimm, Christian Puelacher, Zaid Sabti, Dayana Flores Widmer, Nicolas Schaerli, Nikola Kozhuharov, Samyut Shrestha, Òscar Miró, Beatriz López, Eva Ganovská, Jiri Parenica & Christian Mueller

    4. Laboratory Medicine, University Hospital Basel, Basel, Switzerland

      Katharina Rentsch

    5. Emergency Department, Hospital Clinic, Barcelona, Catalonia, Spain

      Òscar Miró & Beatriz López

    6. Servicio de Urgencias, Hospital Clínico San Carlos, Madrid, Spain

      F. Javier Martin-Sanchez & Esther Rodriguez-Adrada

    7. 2nd Department of Cardiology, Medical University of Silesia, Zabrze, Poland

      Beata Morawiec & Damian Kawecki

    8. Department of Cardiology, University Hospital Brno, Brno, Czech Republic

      Eva Ganovská & Jiri Parenica

    9. Medical Faculty, Masaryk University, Brno, Czech Republic

      Eva Ganovská & Jiri Parenica

    10. Blood Transfusion Centre, Swiss Red Cross, Basel, Switzerland

      Andreas Buser

    11. Department of Hematology, University Hospital Basel, Basel, Switzerland

      Andreas Buser

    12. Emergency Department, University Hospital Zurich, Zurich, Switzerland

      Dagmar I. Keller

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    1. Jasper Boeddinghaus
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    Conflict of interest

    The authors designed the study, gathered, and analyzed the data, vouched for the data and analysis, wrote the paper, and decided to publish. Drs. Boeddinghaus, Reichlin, and Mueller had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors have read and approved the manuscript. The sponsors had no role in designing or conducting the study and no role in gathering or analyzing the data or writing the manuscript. The manuscript and its contents have not been published previously and are not being considered for publications elsewhere in whole or in part in any language, including publicly accessible web sites or e-print servers. We disclose that Dr. Mueller has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, Abbott, Alere, Brahms, Nanosphere, Roche, Siemens, 8sense, Nanosphere, and the Department of Internal Medicine, University Hospital Basel, as well as speaker honoraria from Abbott, Alere, Brahms, Novartis, Roche, and Siemens. Dr. Reichlin has received research grants from the Goldschmidt-Jacobson-Foundation, the Swiss National Science Foundation (PASMP3-136995), the Swiss Heart Foundation, the Professor Max Cloëtta Foundation, the Uniscientia Foundation Vaduz, the University of Basel and the Department of Internal Medicine, University Hospital Basel as well as speaker honoraria from Brahms and Roche. Dr. Rubini received speakers honoraria from Abbott. All other authors declare that they have no conflict of interest with this study.

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    J. Boeddinghaus and T. Reichlin contributed equally to this manuscript and should be considered first author.

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    Boeddinghaus, J., Reichlin, T., Nestelberger, T. et al. Early diagnosis of acute myocardial infarction in patients with mild elevations of cardiac troponin. Clin Res Cardiol 106, 457–467 (2017). https://doi.org/10.1007/s00392-016-1075-9

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