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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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34. 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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36. 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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37. 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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38. Insulin resistance in Takotsubo syndrome.

Author

Bruns, Bastian, Joos, Maximilian, Elsous, Nesrin, Katus, Hugo A., Schultz, Jobst‐Hendrik, Frey, Norbert, Backs, Johannes, and Meder, Benjamin

Subjects
MYOCARDIAL infarction, BLOOD sugar, MANN Whitney U Test, INSULIN therapy, VENTRICULAR ejection fraction, INSULIN resistance
Abstract

Aims: Takotsubo syndrome (TTS) is an acute heart failure (AHF) syndrome mimicking the symptoms of acute myocardial infarction. Impaired outcome has been shown, making risk stratification and novel therapeutic concepts a necessity. We hypothesized insulin resistance with elevated plasma glucose and potentially myocardial glucose deprivation to contribute to the pathogenesis of TTS and investigated the therapeutic benefit of insulin in vivo. Methods and results: First, we retrospectively analysed patient data of n = 265 TTS cases (85.7% female, mean age 71.1 ± 14.1 years) with documented initial plasma glucose from the Department of Cardiology of the University Hospital Heidelberg in Germany (May 2011 to May 2021). Median split of the study population according to glucose levels (≤123 mg/dL vs. >123 mg/dL) yielded significantly elevated mean heart rate (80.75 ± 18.96 vs. 90.01 ± 22.19 b.p.m., P < 0.001), left ventricular end‐diastolic pressure (LVEDP, 18.51 ± 8.35 vs. 23.09 ± 7.97 mmHg, P < 0.001), C‐reactive protein (26.14 ± 43.30 vs. 46.4 ± 68.6 mg/L, P = 0.006), leukocyte count (10.12 ± 4.29 vs. 15.05 ± 9.83/nL, P < 0.001), peak high‐sensitive Troponin T (hs‐TnT, 515.44 ± 672.15 vs. 711.40 ± 736.37 pg/mL, P = 0.005), reduced left ventricular ejection fraction (EF, 34.92 ± 8.94 vs. 31.35 ± 8.06%, P < 0.001), and elevated intrahospital mortality (2.3% vs. 12.1%, P = 0.002) in the high‐glucose group (Student's t‐test, Mann–Whitney U test, or chi‐squared test). Linear regression indicated a significant association of glucose with HR (P < 0.001), LVEDP (P = 0.014), hs‐TnT kinetics from admission to the next day (P < 0.001), hs‐TnT the day after admission (P < 0.001), as well as peak hsTnT (P < 0.001). Logistic regression revealed significant association of glucose with a composite intrahospital outcome including catecholamine use, respiratory support, and resuscitation [OR 1.010 (1.004–1.015), P = 0.001]. To further investigate the potential role of glucose in TTS pathophysiology experimentally, we utilized an in vivo murine model of epinephrine (EPI)‐driven reversible AHF. For this, male mice underwent therapeutic injection of insulin (INS, 1 IU/kg) or/and glucose (GLU, 0.5 g/kg) after EPI (2.5 mg/kg), both of which markedly improved mean EF (EPI 34.3% vs. EPI + INS + GLU 43.7%, P = 0.025) and significantly blunted mean hs‐TnT (EPI 14 393 pg/mL vs. EPI + INS 6864 pg/mL at 24 h, P = 0.039). Particularly, insulin additionally ameliorated myocardial pro‐inflammatory gene expression, suggesting an anti‐inflammatory effect of acute insulin therapy. Conclusions: Elevated initial plasma glucose was associated with adverse outcome‐relevant parameters in TTS and may present a surrogate parameter of heightened catecholaminergic drive. In mice, insulin‐ and glucose injection both improved EPI‐induced AHF and myocardial damage, indicating insulin resistance rather than detrimental effects of hyperglycaemia itself as the underlying cause. Future studies will investigate the role of HbA1c as a risk stratifier and of insulin‐based therapy in TTS. [ABSTRACT FROM AUTHOR]

Published
2024
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39. A complex intervention to promote prevention of delirium in older adults by targeting caregiver’s participation during and after hospital discharge – study protocol of the TRAnsport and DElirium in older people (TRADE) project

Author

Leinert, Christoph, Brefka, Simone, Braisch, Ulrike, Denninger, Natascha, Mueller, Martin, Benzinger, Petra, Bauer, Juergen, Bahrmann, Anke, Frey, Norbert, Katus, Hugo A., Geisler, Tobias, Eschweiler, Gerhard, Klaus, Jochen, Seufferlein, Thomas, Schuetze, Konrad, Gebhard, Florian, Dreyhaupt, Jens, Muche, Rainer, Pahmeier, Kathrin, Biermann-Stallwitz, Janine, Wasem, Juergen, Flagmeier, Lena, Dallmeier, Dhayana, and Denkinger, Michael

Published
2021
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42. Epigenetic regulation of cardiac electrophysiology in atrial fibrillation: HDAC2 determines action potential duration and suppresses NRSF in cardiomyocytes

Author

Lugenbiel, Patrick, Govorov, Katharina, Syren, Pascal, Rahm, Ann-Kathrin, Wieder, Teresa, Wunsch, Maximilian, Weiberg, Nadine, Manolova, Emili, Gramlich, Dominik, Rivinius, Rasmus, Finke, Daniel, Lehmann, Lorenz H., Schweizer, Patrick A., Frank, Derk, El Tahry, Fadwa A., Bruehl, Claus, Heimberger, Tanja, Sandke, Steffi, Weis, Tanja, Most, Patrick, Schmack, Bastian, Ruhparwar, Arjang, Karck, Matthias, Frey, Norbert, Katus, Hugo A., and Thomas, Dierk

Published
2021
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48. Improving sudden cardiac death risk stratification in hypertrophic cardiomyopathy using established clinical variables and genetic information

Author

Amr, Ali, primary, Koelemen, Jan, additional, Reich, Christoph, additional, Sedaghat-Hamedani, Farbod, additional, Kayvanpour, Elham, additional, Haas, Jan, additional, Frese, Karen, additional, Lehmann, David, additional, Katus, Hugo A., additional, Frey, Norbert, additional, and Meder, Benjamin, additional

Published
2023
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