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2. Cardiomuscular Biomarkers in the Diagnosis and Prognostication of Immune Checkpoint Inhibitor Myocarditis.

Author

Lehmann, Lorenz, Heckmann, Markus, Bailly, Guillaume, Finke, Daniel, Procureur, Adrien, Power, John, Stein, Frederic, Bretagne, Marie, Ederhy, Stephane, Fenioux, Charlotte, Hamwy, Omar, Funck-Brentano, Elisa, Romano, Emanuela, Pieroni, Laurence, Münster, Jan, Allenbach, Yves, Anquetil, Céline, Leonard-Louis, Sarah, Palaskas, Nicolas, Hayek, Salim, Katus, Hugo, Giannitsis, Evangelos, Frey, Norbert, Kaya, Ziya, Moslehi, Javid, Prifti, Edi, and Salem, Joe-Elie

Subjects
biomarkers, drug-related side effects and adverse reactions, immune checkpoint inhibitors, myocarditis, pharmacology, troponins, Humans, Myocarditis, Immune Checkpoint Inhibitors, Biomarkers, Creatine Kinase, Prognosis, Troponin T
Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) are approved for multiple cancers but can result in ICI-associated myocarditis, an infrequent but life-threatening condition. Elevations in cardiac biomarkers, specifically troponin-I (cTnI), troponin-T (cTnT), and creatine kinase (CK), are used for diagnosis. However, the association between temporal elevations of these biomarkers with disease trajectory and outcomes has not been established. METHODS: We analyzed the diagnostic accuracy and prognostic performances of cTnI, cTnT, and CK in patients with ICI myocarditis (n=60) through 1-year follow-up in 2 cardio-oncology units (APHP Sorbonne, Paris, France and Heidelberg, Germany). A total of 1751 (1 cTnT assay type), 920 (4 cTnI assay types), and 1191 CK sampling time points were available. Major adverse cardiomyotoxic events (MACE) were defined as heart failure, ventricular arrhythmia, atrioventricular or sinus block requiring pacemaker, respiratory muscle failure requiring mechanical ventilation, and sudden cardiac death. Diagnostic performance of cTnI and cTnT was also assessed in an international ICI myocarditis registry. RESULTS: Within 72 hours of admission, cTnT, cTnI, and CK were increased compared with upper reference limits (URLs) in 56 of 57 (98%), 37 of 42 ([88%] P=0.03 versus cTnT), and 43 of 57 ([75%] P

Published
2023

4. Transient Inhibition of Translation Improves Cardiac Function After Ischemia/Reperfusion by Attenuating the Inflammatory Response

Author

Hofmann, Christoph, Serafin, Adrian, Schwerdt, Ole M., Fischer, Johannes, Sicklinger, Florian, Younesi, Fereshteh S., Byrne, Nikole J., Meyer, Ingmar S., Malovrh, Ellen, Sandmann, Clara, Jürgensen, Lonny, Kamuf-Schenk, Verena, Stroh, Claudia, Löwenthal, Zoe, Finke, Daniel, Boileau, Etienne, Beisaw, Arica, Bugger, Heiko, Rettel, Mandy, Stein, Frank, Katus, Hugo A., Jakobi, Tobias, Frey, Norbert, Leuschner, Florian, and Völkers, Mirko

Published
2024
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7. The DZHK research platform: maximisation of scientific value by enabling access to health data and biological samples collected in cardiovascular clinical studies

Author

Hoffmann, Julia, Hanß, Sabine, Kraus, Monika, Schaller, Jens, Schäfer, Christian, Stahl, Dana, Anker, Stefan D., Anton, Gabriele, Bahls, Thomas, Blankenberg, Stefan, Blumentritt, Arne, Boldt, Leif-Hendrik, Cordes, Steffen, Desch, Steffen, Doehner, Wolfram, Dörr, Marcus, Edelmann, Frank, Eitel, Ingo, Endres, Matthias, Engelhardt, Stefan, Erdmann, Jeanette, Eulenburg, Katharina, Falk, Volkmar, Felix, Stephan B., Frank, Derk, Franke, Thomas, Frey, Norbert, Friede, Tim, Geidel, Lars, Germans, Lisa, Grabmaier, Ulrich, Halle, Martin, Hausleiter, Jörg, Jakobi, Vera, Jebran, Ahmad-Fawad, Jobs, Alexander, Kääb, Stefan, Karakas, Mahir, Katus, Hugo A., Klatt, Alexandra, Knosalla, Christoph, Krebser, Joachim, Landmesser, Ulf, Lee, Mahsa, Lehnert, Kristin, Lesser, Stephanie, Leyh, Katrin, Lorbeer, Roberto, Mach-Kolb, Stephanie, Meder, Benjamin, Nagel, Eike, Nolte, Christian H., Parwani, Abdul S., Petersmann, Astrid, Puls, Miriam, Rau, Henriette, Reiser, Maximilian, Rienhoff, Otto, Scharfe, Tabea, Schattschneider, Mario, Scheel, Heiko, Schnabel, Renate B., Schuster, Andreas, Schmitt, Boris, Seidler, Tim, Seiffert, Moritz, Stähli, Barbara-Elisabeth, Stas, Adriane, J. Stocker, Thomas, von Stülpnagel, Lukas, Thiele, Holger, Wachter, Rolf, Wakili, Reza, Weis, Tanja, Weitmann, Kerstin, Wichmann, Heinz-Erich, Wild, Philipp, Zeller, Tanja, Hoffmann, Wolfgang, Zeisberg, Elisabeth Maria, Zimmermann, Wolfram-Hubertus, Krefting, Dagmar, Kühne, Titus, Peters, Annette, Hasenfuß, Gerd, Massberg, Steffen, Sommer, Thomas, Dimmeler, Stefanie, Eschenhagen, Thomas, and Nauck, Matthias

Published
2023
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10. eCardiology: a structured approach to foster the digital transformation of cardiovascular medicine: Position statement of the German Society of Cardiology

Author

Meder, Benjamin, Duncker, David, Helms, Thomas M., Leistner, David M., Goss, Franz, Perings, Christian, Johnson, Victoria, Freund, Anne, Reich, Christoph, Ledwoch, Jakob, Rahm, Ann-Kathrin, Milles, Barbara Ruth, Perings, Stefan, Pöss, Janine, Dieterich, Christoph, Fleck, Eckart, Breitbart, Philipp, Dutzmann, Jochen, Diller, Gerhard, Thiele, Holger, Frey, Norbert, Katus, Hugo A., and Radke, Peter

Published
2023
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11. eCardiology: ein strukturierter Ansatz zur Förderung der digitalen Transformation in der Kardiologie: Positionspapier der Deutschen Gesellschaft für Kardiologie

Author

Meder, Benjamin, Duncker, David, Helms, Thomas M., Leistner, David M., Goss, Franz, Perings, Christian, Johnson, Victoria, Freund, Anne, Reich, Christoph, Ledwoch, Jakob, Rahm, Ann-Kathrin, Milles, Barbara Ruth, Perings, Stefan, Pöss, Janine, Dieterich, Christoph, Fleck, Eckart, Breitbart, Philipp, Dutzmann, Jochen, Diller, Gerhard, Thiele, Holger, Frey, Norbert, Katus, Hugo A., and Radke, Peter

Published
2023
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16. Prediction of diagnosis and diastolic filling pressure by AI-enhanced cardiac MRI: a modelling study of hospital data

Author

Lehmann, David Hermann, primary, Gomes, Bruna, additional, Vetter, Niklas, additional, Braun, Olivia, additional, Amr, Ali, additional, Hilbel, Thomas, additional, Müller, Jens, additional, Köthe, Ulrich, additional, Reich, Christoph, additional, Kayvanpour, Elham, additional, Sedaghat-Hamedani, Farbod, additional, Meder, Manuela, additional, Haas, Jan, additional, Ashley, Euan, additional, Rottbauer, Wolfgang, additional, Felbel, Dominik, additional, Bekeredjian, Raffi, additional, Mahrholdt, Heiko, additional, Keller, Andreas, additional, Ong, Peter, additional, Seitz, Andreas, additional, Hund, Hauke, additional, Geis, Nicolas, additional, André, Florian, additional, Engelhardt, Sandy, additional, Katus, Hugo A, additional, Frey, Norbert, additional, Heuveline, Vincent, additional, and Meder, Benjamin, additional

Published
2024
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17. Controlling my genome with my smartphone: first clinical experiences of the PROMISE system

Author

Amr, Ali, Hinderer, Marc, Griebel, Lena, Deuber, Dominic, Egger, Christoph, Sedaghat-Hamedani, Farbod, Kayvanpour, Elham, Huhn, Daniel, Haas, Jan, Frese, Karen, Schweig, Marc, Marnau, Ninja, Krämer, Annika, Durand, Claudia, Battke, Florian, Prokosch, Hans-Ulrich, Backes, Michael, Keller, Andreas, Schröder, Dominique, Katus, Hugo A., Frey, Norbert, and Meder, Benjamin

Published
2022
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18. Cathepsin S Levels and Survival Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes

Author

Stamatelopoulos, Kimon, Mueller-Hennessen, Matthias, Georgiopoulos, Georgios, Lopez-Ayala, Pedro, Sachse, Marco, Vlachogiannis, Nikolaos I., Sopova, Kateryna, Delialis, Dimitrios, Bonini, Francesca, Patras, Raphael, Ciliberti, Giorgia, Vafaie, Mehrshad, Biener, Moritz, Boeddinghaus, Jasper, Nestelberger, Thomas, Koechlin, Luca, Tual-Chalot, Simon, Kanakakis, Ioannis, Gatsiou, Aikaterini, Katus, Hugo, Spyridopoulos, Ioakim, Mueller, Christian, Giannitsis, Evangelos, and Stellos, Konstantinos

Published
2022
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23. NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart

Author

Müller, Marion, Eghbalian, Rose, Boeckel, Jes-Niels, Frese, Karen S., Haas, Jan, Kayvanpour, Elham, Sedaghat-Hamedani, Farbod, Lackner, Maximilian K., Tugrul, Oguz F., Ruppert, Thomas, Tappu, Rewati, Martins Bordalo, Diana, Kneuer, Jasmin M., Piekarek, Annika, Herch, Sabine, Schudy, Sarah, Keller, Andreas, Grammes, Nadja, Bischof, Cornelius, Klinke, Anna, Cardoso-Moreira, Margarida, Kaessmann, Henrik, Katus, Hugo A., Frey, Norbert, Steinmetz, Lars M., and Meder, Benjamin

Published
2022
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25. Skeletal muscle derived Musclin protects the heart during pathological overload

Author

Szaroszyk, Malgorzata, Kattih, Badder, Martin-Garrido, Abel, Trogisch, Felix A., Dittrich, Gesine M., Grund, Andrea, Abouissa, Aya, Derlin, Katja, Meier, Martin, Holler, Tim, Korf-Klingebiel, Mortimer, Völker, Katharina, Garfias Macedo, Tania, Pablo Tortola, Cristina, Boschmann, Michael, Huang, Nora, Froese, Natali, Zwadlo, Carolin, Malek Mohammadi, Mona, Luo, Xiaojing, Wagner, Michael, Cordero, Julio, Geffers, Robert, Batkai, Sandor, Thum, Thomas, Bork, Nadja, Nikolaev, Viacheslav O., Müller, Oliver J., Katus, Hugo A., El-Armouche, Ali, Kraft, Theresia, Springer, Jochen, Dobreva, Gergana, Wollert, Kai C., Fielitz, Jens, von Haehling, Stephan, Kuhn, Michaela, Bauersachs, Johann, and Heineke, Joerg

Published
2022
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26. Effect of impaired kidney function on outcomes and treatment effects of oral anticoagulant regimes in patients with atrial fibrillation in a real-world registry.

Author

Salbach, Christian, Milles, Barbara Ruth, Hund, Hauke, Biener, Moritz, Mueller-Hennessen, Matthias, Frey, Norbert, Katus, Hugo, Giannitsis, Evangelos, and Yildirim, Mustafa

Subjects
ORAL medication, KIDNEY physiology, MYOCARDIAL infarction, MORTALITY, STROKE, ATRIAL fibrillation
Abstract

Background: The impact of impaired kidney function on outcomes and treatment benefits of vitamin-K antagonists (VKA) versus direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) has insufficiently been investigated in randomized controlled studies (RCTs). Most studies and registries are either biased due to incomplete enrolment of consecutive patients in large pharma industry sponsored registries, or due to short recruitment periods or incomplete assessment of important variables in national registries. Methods: This study uses data from the Heidelberg Registry of Atrial Fibrillation (HERA-FIB), a retrospective single-center registry of 10,222 consecutive patients with AF presenting to the emergency department of University Hospital of Heidelberg from June 2009 until March 2020. Rates of all-cause mortality, stroke, major bleeding and myocardial infarction (MI) were related to the presence and severity of impaired presenting kidney function, as well as to assigned treatment with VKA vs. DOAC. Results: The risks for all-cause mortality (HR: 3.26, p<0.001), stroke (HR: 1.58, p<0.001), major bleeding (HR: 2.28, p<0.001) and MI (HR: 2.48, p<0.001) were significantly higher in patients with an eGFR<60 ml/min at admission and increased with decreasing eGFR. After adjustment for variables of CHA2DS2VASc-score, presence of eGFR <60 ml/min remained as an independent predictor for all-cause mortality, major bleeding and MI. The hazard ratio (HR) for all-cause mortality, major bleedings and MI was significantly lower in patients receiving DOAC compared to VKA. Conclusion: Findings from our large real-life registry confirm the data from RCTs and extend our knowledge on the effectiveness and safety of DOACs to subjects that were underrepresented in RCTs. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Ethnic comparison in takotsubo syndrome: novel insights from the International Takotsubo Registry

Author

Imori, Yoichi, Kato, Ken, Cammann, Victoria L., Szawan, Konrad A., Wischnewsky, Manfred, Dreiding, Sara, Würdinger, Michael, Schönberger, Maximilian, Petkova, Vanya, Niederseer, David, Levinson, Rena A., Di Vece, Davide, Gili, Sebastiano, Seifert, Burkhardt, Wakita, Masaki, Suzuki, Noriko, Citro, Rodolfo, Bossone, Eduardo, Heiner, Susanne, Knorr, Maike, Jansen, Thomas, Münzel, Thomas, D’Ascenzo, Fabrizio, Franke, Jennifer, Sorici-Barb, Ioana, Katus, Hugo A., Sarcon, Annahita, Shinbane, Jerold, Napp, L. Christian, Bauersachs, Johann, Jaguszewski, Milosz, Shiomura, Reiko, Nakamura, Shunichi, Takano, Hitoshi, Noutsias, Michel, Burgdorf, Christof, Ishibashi, Iwao, Himi, Toshiharu, Koenig, Wolfgang, Schunkert, Heribert, Thiele, Holger, Kherad, Behrouz, Tschöpe, Carsten, Pieske, Burkert M., Rajan, Lawrence, Michels, Guido, Pfister, Roman, Mizuno, Shingo, Cuneo, Alessandro, Jacobshagen, Claudius, Hasenfuß, Gerd, Karakas, Mahir, Mochizuki, Hiroki, Pott, Alexander, Rottbauer, Wolfgang, Said, Samir M., Braun-Dullaeus, Ruediger C., Banning, Adrian, Isogai, Toshiaki, Kimura, Akihisa, Cuculi, Florim, Kobza, Richard, Fischer, Thomas A., Vasankari, Tuija, Airaksinen, K. E. Juhani, Tomita, Yasuhiro, Budnik, Monika, Opolski, Grzegorz, Dworakowski, Rafal, MacCarthy, Philip, Kaiser, Christoph, Osswald, Stefan, Galiuto, Leonarda, Crea, Filippo, Dichtl, Wolfgang, Murakami, Tsutomu, Ikari, Yuji, Empen, Klaus, Beug, Daniel, Felix, Stephan B., Delmas, Clément, Lairez, Olivier, Yamaguchi, Tetsuo, El-Battrawy, Ibrahim, Akin, Ibrahim, Borggrefe, Martin, Horowitz, John D., Kozel, Martin, Tousek, Petr, Widimský, Petr, Gilyarova, Ekaterina, Shilova, Alexandra, Gilyarov, Mikhail, Neuhaus, Michael, Meyer, Philippe, Arroja, Jose David, Chan, Christina, Bridgman, Paul, Galuszka, Jan, Poglajen, Gregor, Carrilho-Ferreira, Pedro, Pinto, Fausto J., Hauck, Christian, Maier, Lars S., Liu, Kan, Di Mario, Carlo, Paolini, Carla, Bilato, Claudio, Bianco, Matteo, Jörg, Lucas, Rickli, Hans, Winchester, David E., Ukena, Christian, Böhm, Michael, Bax, Jeroen J., Prasad, Abhiram, Rihal, Charanjit S., Saito, Shigeru, Kobayashi, Yoshio, Lüscher, Thomas F., Ruschitzka, Frank, Shimizu, Wataru, Ghadri, Jelena R., and Templin, Christian

Published
2022
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30. Manual der Arbeitsgruppe Interventionelle Kardiologie (AGIK) der Deutschen Gesellschaft für Kardiologie – Herz- und Kreislaufforschung e.V. (DGK): Teil 2: „Durchführung der perkutanen Koronarintervention“

Author

Nef, Holger M., Achenbach, Stephan, Birkemeyer, Ralf, Bufe, Alexander, Dörr, Oliver, Elsässer, Albrecht, Gaede, Luise, Gori, Tommaso, Hoffmeister, Hans M., Hofmann, Felix J., Katus, Hugo A., Liebetrau, Christoph, Massberg, Steffen, Pauschinger, Matthias, Schmitz, Thomas, Süselbeck, Tim, Voelker, Wolfram, Wiebe, Jens, Zahn, Ralf, Hamm, Christian, Zeiher, Andreas M., and Möllmann, Helge

Published
2021
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37. A Self-Taught Artificial Agent for Multi-Physics Computational Model Personalization

Author

Neumann, Dominik, Mansi, Tommaso, Itu, Lucian, Georgescu, Bogdan, Kayvanpour, Elham, Sedaghat-Hamedani, Farbod, Amr, Ali, Haas, Jan, Katus, Hugo, Meder, Benjamin, Steidl, Stefan, Hornegger, Joachim, and Comaniciu, Dorin

Subjects
Computer Science - Computational Engineering, Finance, and Science, Computer Science - Artificial Intelligence
Abstract

Personalization is the process of fitting a model to patient data, a critical step towards application of multi-physics computational models in clinical practice. Designing robust personalization algorithms is often a tedious, time-consuming, model- and data-specific process. We propose to use artificial intelligence concepts to learn this task, inspired by how human experts manually perform it. The problem is reformulated in terms of reinforcement learning. In an off-line phase, Vito, our self-taught artificial agent, learns a representative decision process model through exploration of the computational model: it learns how the model behaves under change of parameters. The agent then automatically learns an optimal strategy for on-line personalization. The algorithm is model-independent; applying it to a new model requires only adjusting few hyper-parameters of the agent and defining the observations to match. The full knowledge of the model itself is not required. Vito was tested in a synthetic scenario, showing that it could learn how to optimize cost functions generically. Then Vito was applied to the inverse problem of cardiac electrophysiology and the personalization of a whole-body circulation model. The obtained results suggested that Vito could achieve equivalent, if not better goodness of fit than standard methods, while being more robust (up to 11% higher success rates) and with faster (up to seven times) convergence rate. Our artificial intelligence approach could thus make personalization algorithms generalizable and self-adaptable to any patient and any model., Comment: Submitted to Medical Image Analysis, Elsevier

Published
2016

40. Combined non-invasive assessment of endothelial shear stress and molecular imaging of inflammation for the prediction of inflamed plaque in hyperlipidaemic rabbit aortas

Author

Gitsioudis, Gitsios, Chatzizisis, Yiannis S, Wolf, Peter, Missiou, Anna, Antoniadis, Antonios P, Mitsouras, Dimitrios, Bartling, Sönke, Arica, Zeynep, Stuber, Matthias, Rybicki, Frank J, Nunninger, Max, Erbel, Christian, Libby, Peter, Giannoglou, George D, Katus, Hugo A, and Korosoglou, Grigorios

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Biomedical Imaging, Atherosclerosis, Bioengineering, Animals, Aorta, Biopsy, Needle, Computed Tomography Angiography, Confidence Intervals, Disease Models, Animal, Disease Progression, Endothelium, Vascular, Hyperlipidemias, Immunohistochemistry, Inflammation, Linear Models, Magnetic Resonance Imaging, Male, Molecular Imaging, Observer Variation, Plaque, Atherosclerotic, Predictive Value of Tests, ROC Curve, Rabbits, Random Allocation, Reproducibility of Results, Sensitivity and Specificity, Shear Strength, Ultrasonography, Interventional, atherosclerosis, hyperlipidaemic rabbits, endothelial shear stress, molecular imaging, magnetic resonance imaging, computed tomography angiography, Cardiovascular medicine and haematology
Abstract

AimsTo evaluate the incremental value of low endothelial shear stress (ESS) combined with high-resolution magnetic resonance imaging (MRI)- and computed tomography angiography (CTA)-based imaging for the prediction of inflamed plaque.Methods and resultsTwelve hereditary hyperlipidaemic rabbits underwent quantitative analysis of plaque in the thoracic aorta with 256-slice CTA and USPIO-enhanced (ultra-small superparamagnetic nanoparticles, P904) 1.5-T MRI at baseline and at 6-month follow-up. Computational fluid dynamics using CTA-based 3D reconstruction of thoracic aortas identified the ESS patterns in the convex and concave curvature subsegments of interest. Subsegments with low baseline ESS exhibited significant increase in wall thickness and plaque inflammation by MRI, in non-calcified plaque burden by CTA, and developed increased plaque size, lipid and inflammatory cell accumulation (high-risk plaque features) at follow-up by histopathology. Multiple regression analysis identified baseline ESS and inflammation by MRI to be independent predictors of plaque progression, while receiver operating curve analysis revealed baseline ESS alone or in combination with inflammation by MRI as the strongest predictor for augmented plaque burden and inflammation (low ESS at baseline: AUC = 0.84, P < 0.001; low ESS and inflammation by molecular MRI at baseline: AUC = 0.89, P < 0.001).ConclusionLow ESS predicts progression of plaque burden and inflammation as assessed by non-invasive USPIO-enhanced MRI. Combined non-invasive assessment of ESS and imaging of inflammation may serve to predict plaque with high-risk features.

Published
2017

41. Manual der Arbeitsgruppe Interventionelle Kardiologie (AGIK) der Deutschen Gesellschaft für Kardiologie – Herz- und Kreislaufforschung e. V. (DGK): Teil 1: „Durchführung der diagnostischen Herzkatheteruntersuchung“

Author

Nef, Holger M., Achenbach, Stephan, Birkemeyer, Ralf, Bufe, Alexander, Dörr, Oliver, Elsässer, Albrecht, Gaede, Luise, Gori, Tommaso, Hoffmeister, Hans M., Hofmann, Felix J., Katus, Hugo A., Liebetrau, Christoph, Massberg, Steffen, Pauschinger, Matthias, Schmitz, Thomas, Süselbeck, Tim, Voelker, Wolfram, Wiebe, Jens, Zahn, Ralf, Hamm, Christian, Zeiher, Andreas M., and Möllmann, Helge

Published
2021
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44. microRNA neural networks improve diagnosis of acute coronary syndrome (ACS)

Author

Kayvanpour, Elham, Gi, Weng-Tein, Sedaghat-Hamedani, Farbod, Lehmann, David H., Frese, Karen S., Haas, Jan, Tappu, Rewati, Samani, Omid Shirvani, Nietsch, Rouven, Kahraman, Mustafa, Fehlmann, Tobias, Müller-Hennessen, Matthias, Weis, Tanja, Giannitsis, Evangelos, Niederdränk, Torsten, Keller, Andreas, Katus, Hugo A., and Meder, Benjamin

Published
2021
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45. Temporal biomarker concentration patterns during the early course of acute coronary syndrome

Author

Eggers, Kai M., Batra, Gorav, Lindahl, Bertil, Lakic, Tatevik, Lindbäck, Johan, Budaj, Andrzej, Cornel, Jan H., Giannitsis, Evangelos, Katus, Hugo A., Storey, Robert F., Becker, Richard C., Siegbahn, Agneta, Wallentin, Lars, Eggers, Kai M., Batra, Gorav, Lindahl, Bertil, Lakic, Tatevik, Lindbäck, Johan, Budaj, Andrzej, Cornel, Jan H., Giannitsis, Evangelos, Katus, Hugo A., Storey, Robert F., Becker, Richard C., Siegbahn, Agneta, and Wallentin, Lars

Abstract

Objectives: Biomarker concentrations and their changes during acute coronary syndrome (ACS) provide clinically useful information on pathophysiological processes, e.g. myocardial necrosis, hemodynamic stress and inflammation. However, current evidence on temporal biomarker patterns early during ACS is limited, and studies investigating multiple biomarkers are lacking. Methods: We measured concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI), NT-terminal pro-B-type natriuretic peptide, C-reactive protein, and growth-differentiation factor-15 (GDF-15) in plasma samples obtained at randomization in ACS patients from the PLATelet inhibition and patient Outcomes (PLATO) trial. Linear regressions with interaction analyses were used to investigate the associations of biomarker concentrations with the time from symptom onset and to model temporal biomarker concentration patterns. Results: The study population consisted of 16,944 patients (median age 62 years; 71.3 % males) with 6,853 (40.3 %) having ST-elevation myocardial infarction (STEMI) and 10,141 (59.7 %) having non-ST-elevation ACS (NSTE-ACS). Concentrations of all biomarkers were associated with time from symptom onset (pinteraction<0.001), apart for GDF-15 (pinteraction=0.092). Concentration increases were more pronounced in STEMI compared to NSTE-ACS. Temporal biomarker patterns for hs-cTnT and hs-cTnI were different depending on sex whereas biomarker patterns for the other biomarkers were similar in cohorts defined by age and sex. Conclusions: Temporal concentration patterns differ for various biomarkers early during ACS, reflecting the variability in the activation and duration of different pathophysiological processes, and the amount of injured myocardium. Our data emphasize that the time elapsed from symptom onset should be considered for the interpretation of biomarker results in ACS.

Published
2024
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