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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. 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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9. 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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10. 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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15. 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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16. 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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20. 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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24. 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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26. 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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28. S100A1's single cysteine is an indispensable redox switch for the protection against diastolic calcium waves in cardiomyocytes.

Author

Seitz, Andreas, Busch, Martin, Kroemer, Jasmin, Schneider, Andrea, Simon, Stephanie, Jungmann, Andreas, Katus, Hugo A., Most, Patrick, and Ritterhoff, Julia

Subjects
RYANODINE receptors, REACTIVE nitrogen species, CALCIUM, POST-translational modification, SARCOPLASMIC reticulum
Abstract

The EF-hand calcium (Ca2+) sensor protein S100A1 combines inotropic with antiarrhythmic potency in cardiomyocytes (CMs). Oxidative posttranslational modification (ox-PTM) of S100A1's conserved, single-cysteine residue (C85) via reactive nitrogen species (i.e., S-nitrosylation or S-glutathionylation) has been proposed to modulate conformational flexibility of intrinsically disordered sequence fragments and to increase the molecule's affinity toward Ca2+. Considering the unknown biological functional consequence, we aimed to determine the impact of the C85 moiety of S100A1 as a potential redox switch. We first uncovered that S100A1 is endogenously glutathionylated in the adult heart in vivo. To prevent glutathionylation of S100A1, we generated S100A1 variants that were unresponsive to ox-PTMs. Overexpression of wild-type (WT) and C85-deficient S100A1 protein variants in isolated CM demonstrated equal inotropic potency, as shown by equally augmented Ca2+ transient amplitudes under basal conditions and β-adrenergic receptor (βAR) stimulation. However, in contrast, ox-PTM defective S100A1 variants failed to protect against arrhythmogenic diastolic sarcoplasmic reticulum (SR) Ca2+ waves and ryanodine receptor 2 (RyR2) hypernitrosylation during βAR stimulation. Despite diastolic performance failure, C85-deficient S100A1 protein variants exerted similar Ca2+-dependent interaction with the RyR2 than WT-S100A1. Dissecting S100A1's molecular structure-function relationship, our data indicate for the first time that the conserved C85 residue potentially acts as a redox switch that is indispensable for S100A1's antiarrhythmic but not its inotropic potency in CMs. We, therefore, propose a model where C85's ox-PTM determines S100A1's ability to beneficially control diastolic but not systolic RyR2 activity. NEW & NOTEWORTHY: S100A1 is an emerging candidate for future gene-therapy treatment of human chronic heart failure. We aimed to study the significance of the conserved single-cysteine 85 (C85) residue in cardiomyocytes. We show that S100A1 is endogenously glutathionylated in the heart and demonstrate that this is dispensable to increase systolic Ca2+ transients, but indispensable for mediating S100A1's protection against sarcoplasmic reticulum (SR) Ca2+ waves, which was dependent on the ryanodine receptor 2 (RyR2) nitrosylation status. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Type 1 Myocardial Infarction in Patients With Acute Ischemic Stroke.

Author

Nolte, Christian H., von Rennenberg, Regina, Litmeier, Simon, Leistner, David M., Szabo, Kristina, Baumann, Stefan, Mengel, Annerose, Michalski, Dominik, Siepmann, Timo, Blankenberg, Stephan, Petzold, Gabor C., Dichgans, Martin, Katus, Hugo, Pieske, Burkert, Regitz-Zagrosek, Vera, Braemswig, Tim Bastian, Rangus, Ida, Pepic, Amra, Vettorazzi, Eik, and Zeiher, Andreas M.

Published
2024
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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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38. 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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39. 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

42. 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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43. 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

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