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152. Basophils balance healing after myocardial infarction via IL-4/IL-13

Author

Sicklinger, Florian, Meyer, Ingmar Soren, Li, Xue, Radtke, Daniel, Dicks, Severin, Kornadt, Moritz P., Mertens, Christina, Meier, Julia K., Lavine, Kory J., Zhang, Yunhang, Kuhn, Tim Christian, Terzer, Tobias, Patel, Jyoti, Boerries, Melanie, Schramm, Gabriele, Frey, Norbert, Katus, Hugo A., Voehringer, David, and Leuschner, Florian

Subjects
Heart attack -- Development and progression, Inflammation -- Development and progression, Regeneration (Biology) -- Health aspects -- Physiological aspects, Interleukin-13 -- Health aspects -- Physiological aspects, Basophils -- Health aspects -- Physiological aspects, Interleukin-4 -- Health aspects -- Physiological aspects, Health care industry
Abstract

The inflammatory response after myocardial infarction (MI) is a precisely regulated process that greatly affects subsequent remodeling. Here, we show that basophil granulocytes infiltrated infarcted murine hearts, with a peak occurring between days 3 and 7 Antibody-mediated and genetic depletion of basophils deteriorated cardiac function and resulted in enhanced scar thinning after MI. Mechanistically, we found that basophil depletion was associated with a shift from reparative [Ly6C.sup.lo] macrophages toward increased numbers of inflammatory [Ly6C.sup.hi] monocytes in the infarcted myocardium. Restoration of basophils in basophil-deficient mice by adoptive transfer reversed this proinflammatory phenotype. Cellular alterations in the absence of basophils were accompanied by lower cardiac levels of IL-4 and IL-13, two major cytokines secreted by basophils. Mice with basophil-specific IL-4/IL-13 deficiency exhibited a similarly altered myeloid response with an increased fraction of [Ly6C.sup.hi] monocytes and aggravated cardiac function after MI. In contrast, IL-4 induction in basophils via administration of the glycoprotein IPSE/[alpha]-1 led to improved post-MI healing. These results in mice were corroborated by the finding that initially low counts of blood basophils in patients with acute MI were associated with a worse cardiac outcome after 1 year, characterized by a larger scar size. In conclusion, we show that basophils promoted tissue repair after MI by increasing cardiac IL-4 and IL-13 levels., Introduction Inflammation is an essential mechanism for restoring tissue integrity after myocardial infarction (MI). After restriction of blood supply, the inflammatory response is characterized by a multistep cascade at both [...]

Published
2021
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158. Guía ESC 2020 para el tratamiento de las cardiopatías congénitas del adulto

Author

Baumgartner, Helmut, De Backer, Julie, Babu-Narayan, Sonya V., Budts, Werner, Chessa, Massimo, Diller, Gerhard-Paul, Iung, Bernard, Kluin, Jolanda, Lang, Irene M., Meijboom, Folkert, Moons, Philip, Mulder, Barbara J.M., Oechslin, Erwin, Roos-Hesselink, Jolien W., Schwerzmann, Markus, Sondergaard, Lars, Zeppenfeld, Katja, Ernst, Sabine, Ladouceur, Magalie, Aboyans, Victor, Alexander, David, Christodorescu, Ruxandra, Corrado, Domenico, D’Alto, Michele, de Groot, Natasja, Delgado, Victoria, Di Salvo, Giovanni, Dos Subira, Laura, Eicken, Andreas, Fitzsimons, Donna, Frogoudaki, Alexandra A., Gatzoulis, Michael, Heymans, Stephane, Hörer, Jürgen, Houyel, Lucile, Jondeau, Guillaume, Katus, Hugo A., Landmesser, Ulf, Lewis, Basil S., Lyon, Alexander, Mueller, Christian E., Mylotte, Darren, Petersen, Steffen E., Petronio, Anna Sonia, Roffi, Marco, Rosenhek, Raphael, Shlyakhto, Evgeny, Simpson, Iain A., Sousa-Uva, Miguel, Torp-Pedersen, Christian Tobias, Touyz, Rhian M., and Van De Bruaene, Alexander

Published
2021
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161. Genomic structural variations lead to dysregulation of important coding and non‐coding RNA species in dilated cardiomyopathy

Author

Haas, Jan, Mester, Stefan, Lai, Alan, Frese, Karen S, Sedaghat‐Hamedani, Farbod, Kayvanpour, Elham, Rausch, Tobias, Nietsch, Rouven, Boeckel, Jes‐Niels, Carstensen, Avisha, Völkers, Mirko, Dietrich, Carsten, Pils, Dietmar, Amr, Ali, Holzer, Daniel B, Martins Bordalo, Diana, Oehler, Daniel, Weis, Tanja, Mereles, Derliz, Buss, Sebastian, Riechert, Eva, Wirsz, Emil, Wuerstle, Maximilian, Korbel, Jan O, Keller, Andreas, Katus, Hugo A, Posch, Andreas E, and Meder, Benjamin

Published
2018
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166. Abstract 686: Glp-2 Predicts Cardiovascular Outcomes In Patients With Myocardial Infarction And Increases Atherosclerosis In Mice

Author

Sausen, Maximillian, primary, Mertens, Robert, additional, Quintana, Luis, additional, Rueckbeil, Marcia, additional, Idel, Paul, additional, Tabaza, Nadim, additional, Ganesh, Naresh, additional, Just, Susanne, additional, Arrivas, Maria, additional, Moellmann, Julia, additional, Spießhoefer, Jens, additional, Biener, Moritz B, additional, Giannitsis, Evangelos, additional, Katus, Hugo, additional, Drucker, Daniel J, additional, Marx, Nikolaus, additional, Lehrke, Michael, additional, and Kahles, Florian, additional

Published
2023
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167. Mid-regional pro-adrenomedullin and lactate levels for risk stratification in patients with out-of-hospital cardiac arrest

Author

Zelniker, Thomas A, primary, Schwall, Dominik, additional, Hamidi, Fardin, additional, Steinbach, Simone, additional, Scheller, Pascal, additional, Spaich, Sebastian, additional, Michels, Guido, additional, Giannitsis, Evangelos, additional, Katus, Hugo A, additional, Frey, Norbert, additional, and Preusch, Michael R, additional

Published
2023
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168. Cardiac-targeted rAAV5-S100A1 gene therapy protects against adverse remodeling and contractile dysfunction in post-ischemic hearts

Author

Kehr, Dorothea, primary, Salatzki, Janek, additional, Krautz, Birgit, additional, Varadi, Karl, additional, Birkenstock, Jennifer, additional, Schlegel, Philipp, additional, Gao, Erhe, additional, Koch, Walter J., additional, Riffel, Johannes, additional, André, Florian, additional, Peppel, Karsten, additional, Katus, Hugo, additional, Frey, Norbert, additional, Busch, Martin, additional, Pfannkuche, Helga, additional, Ritterhoff, Julia, additional, Jungmann, Andreas, additional, and Most, Patrick, additional

Published
2023
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169. S100A1ct: a synthetic peptide derived from human S100A1 protein improves cardiac contractile performance and survival in pre-clinical heart failure models

Author

Kehr, Dorothea, primary, Ritterhoff, Julia, additional, Glaser, Manuel, additional, Jarosch, Lukas, additional, Salazar, Rafael E., additional, Spaich, Kristin, additional, Varadi, Karl, additional, Birkenstock, Jennifer, additional, Egger, Michael, additional, Gao, Erhe, additional, Koch, Walter J., additional, Katus, Hugo A., additional, Frey, Norbert, additional, Jungmann, Andreas, additional, Busch, Cornelius, additional, Mather, Paul J., additional, Ruhparwar, Arjang, additional, Völkers, Mirko, additional, Wade, Rebecca C., additional, and Most, Patrick, additional

Published
2023
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170. Biomarker Concentrations and Their Temporal Changes in Patients With Myocardial Infarction and Nonobstructive Compared With Obstructive Coronary Arteries : Results From the PLATO Trial

Author

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

Abstract

Background: The pathobiology of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is often uncertain. Investigating biomarker concentrations and their changes may offer novel pathophysiological insights. Methods and Results: In this post hoc study of the PLATO (Platelet Inhibition and Patient Outcomes) trial, concentrations of hs‐cTnT (high‐sensitivity cardiac troponin T), NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), hs‐CRP (high‐sensitivity C‐reactive protein), and GDF‐15 (growth differentiation factor 15) were measured in patients with MINOCA at baseline (n=554) and at 1‐month follow‐up (n=107). For comparisons, biomarkers were also measured in patients with MI with obstructive (stenosis ≥50%) coronary artery disease (baseline: n=11 106; follow‐up: n=2755]). Adjusted linear regression models were used to compare concentrations and their short‐ and long‐term changes. The adjusted geometric mean ratios (GMRs) in patients with MINOCA (median age, 61 years; 50.4% women) indicated lower hs‐cTnT (GMR, 0.77 [95% CI, 0.68–0.88]) but higher hs‐CRP (GMR, 1.21 [95% CI, 1.08–1.37]) and GDF‐15 concentrations (GMR, 1.06 [95% CI, 1.02–1.11]) at baseline compared with patients with MI with obstructive coronary artery disease, whereas NT‐proBNP concentrations were similar. Temporal decreases in hs‐cTnT, NT‐proBNP, and hs‐CRP concentrations until 1‐month follow‐up were more pronounced in patients with MINOCA. At follow‐up, patients with MINOCA had lower concentrations of hs‐cTnT (GMR, 0.71 [95% CI, 0.60–0.84]), NT‐proBNP (GMR, 0.45 [95% CI, 0.36–0.56]), and hs‐CRP (GMR, 0.68 [95% CI, 0.53–0.86]). One‐month GDF‐15 concentrations were similar between both groups with MI. Conclusions: Biomarker concentrations suggest greater initial inflammatory activity, similar degree of myocardial dysfunction, and less pronounced myocardial injury during the acute phase of MINOCA compared with MI with obstructive coronary artery disease but also faster myocardial r, Title in dissertation list of papers: Biomarker concentrations and their temporal changes in myocardial infarction patients with non-obstructive compared to obstructive coronary arteries: results from the PLATelet inhibition and patient Outcomes (PLATO) trial

Published
2023
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171. Modification of the GRACE Risk Score for Risk Prediction in Patients With Acute Coronary Syndromes

Author

Georgiopoulos, Georgios, Kraler, Simon, Mueller-Hennessen, Matthias, Delialis, Dimitrios, Mavraganis, Georgios, Sopova, Kateryna, Wenzl, Florian A, Räber, Lorenz, Biener, Moritz, Stähli, Barbara E, Maneta, Eleni, Spray, Luke, Iglesias, Juan F, Coelho-Lima, Jose, Tual-Chalot, Simon, Muller, Olivier, Mach, François, Frey, Norbert, Duerschmied, Daniel, Langer, Harald F, Katus, Hugo, Roffi, Marco, Camici, Giovanni G, Mueller, Christian, Giannitsis, Evangelos, Spyridopoulos, Ioakim, Lüscher, Thomas F, Stellos, Konstantinos, Stamatelopoulos, Kimon, Georgiopoulos, Georgios, Kraler, Simon, Mueller-Hennessen, Matthias, Delialis, Dimitrios, Mavraganis, Georgios, Sopova, Kateryna, Wenzl, Florian A, Räber, Lorenz, Biener, Moritz, Stähli, Barbara E, Maneta, Eleni, Spray, Luke, Iglesias, Juan F, Coelho-Lima, Jose, Tual-Chalot, Simon, Muller, Olivier, Mach, François, Frey, Norbert, Duerschmied, Daniel, Langer, Harald F, Katus, Hugo, Roffi, Marco, Camici, Giovanni G, Mueller, Christian, Giannitsis, Evangelos, Spyridopoulos, Ioakim, Lüscher, Thomas F, Stellos, Konstantinos, and Stamatelopoulos, Kimon

Abstract

IMPORTANCE The Global Registry of Acute Coronary Events (GRACE) risk score, a guideline-recommended risk stratification tool for patients presenting with acute coronary syndromes (ACS), does not consider the extent of myocardial injury. OBJECTIVE To assess the incremental predictive value of a modified GRACE score incorporating high-sensitivity cardiac troponin (hs-cTn) T at presentation, a surrogate of the extent of myocardial injury. DESIGN, SETTING, AND PARTICIPANTS This retrospectively designed longitudinal cohort study examined 3 independent cohorts of 9803 patients with ACS enrolled from September 2009 to December 2017; 2 ACS derivation cohorts (Heidelberg ACS cohort and Newcastle STEMI cohort) and an ACS validation cohort (SPUM-ACS study). The Heidelberg ACS cohort included 2535 and the SPUM-ACS study 4288 consecutive patients presenting with a working diagnosis of ACS. The Newcastle STEMI cohort included 2980 consecutive patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Data were analyzed from March to June 2023. EXPOSURES In-hospital, 30-day, and 1-year mortality risk estimates derived from an updated risk score that incorporates continuous hs-cTn T at presentation (modified GRACE). MAIN OUTCOMES AND MEASURES The predictive value of continuous hs-cTn T and modified GRACE risk score compared with the original GRACE risk score. Study end points were all-cause mortality during hospitalization and at 30 days and 1 year after the index event. RESULTS Of 9450 included patients, 7313 (77.4%) were male, and the mean (SD) age at presentation was 64.2 (12.6) years. Using continuous rather than binary hs-cTn T conferred improved discrimination and reclassification compared with the original GRACE score (in-hospital mortality: area under the receiver operating characteristic curve [AUC], 0.835 vs 0.741; continuous net reclassification improvement [NRI], 0.208; 30-day mortality: AUC, 0.828 vs 0.740; NRI, 0.312; 1-y

Published
2023

174. Diagnostic and prognostic implications using age- and gender-specific cut-offs for high-sensitivity cardiac troponin T — Sub-analysis from the TRAPID-AMI study

Author

Mueller-Hennessen, Matthias, Lindahl, Bertil, Giannitsis, Evangelos, Biener, Moritz, Vafaie, Mehrshad, deFilippi, Christopher R., Christ, Michael, Santalo-Bel, Miguel, Panteghini, Mauro, Plebani, Mario, Verschuren, Franck, Jernberg, Tomas, French, John K., Christenson, Robert H., Body, Richard, McCord, James, Dilba, Peter, Katus, Hugo A., and Mueller, Christian

Published
2016
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176. Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia

Author

Schäfer, Michaela, Oeing, Christian U., Rohm, Maria, Baysal-Temel, Ezgi, Lehmann, Lorenz H., Bauer, Ralf, Volz, H. Christian, Boutros, Michael, Sohn, Daniela, Sticht, Carsten, Gretz, Norbert, Eichelbaum, Katrin, Werner, Tessa, Hirt, Marc N., Eschenhagen, Thomas, Müller-Decker, Karin, Strobel, Oliver, Hackert, Thilo, Krijgsveld, Jeroen, Katus, Hugo A., Berriel Diaz, Mauricio, Backs, Johannes, and Herzig, Stephan

Published
2016
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178. Critical role of RAGE and HMGB1 in inflammatory heart disease

Author

Bangert, Anna, Andrassy, Martin, Müller, Anna-Maria, Bockstahler, Mariella, Fischer, Andrea, Volz, Christian H., Leib, Christoph, Göser, Stefan, Korkmaz-Icöz, Sevil, Zittrich, Stefan, Jungmann, Andreas, Lasitschka, Felix, Pfitzer, Gabriele, Müller, Oliver J., Katus, Hugo A., and Kaya, Ziya

Published
2016

179. Robust Image-Based Estimation of Cardiac Tissue Parameters and Their Uncertainty from Noisy Data

Author

Neumann, Dominik, Mansi, Tommaso, Georgescu, Bogdan, Kamen, Ali, Kayvanpour, Elham, Amr, Ali, Sedaghat-Hamedani, Farbod, Haas, Jan, Katus, Hugo, Meder, Benjamin, Hornegger, Joachim, Comaniciu, Dorin, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Kobsa, Alfred, Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Golland, Polina, editor, Hata, Nobuhiko, editor, Barillot, Christian, editor, Hornegger, Joachim, editor, and Howe, Robert, editor

Published
2014
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180. Genetic Ablation of TASK-1 (Tandem of P Domains in a Weak Inward Rectifying K+ Channel–Related Acid-Sensitive K+ Channel-1) (K2P3.1) K+ Channels Suppresses Atrial Fibrillation and Prevents Electrical Remodeling

Author

Schmidt, Constanze, Wiedmann, Felix, Beyersdorf, Christoph, Zhao, Zhihan, El-Battrawy, Ibrahim, Lan, Huan, Szabo, Gabor, Li, Xin, Lang, Siegfried, Korkmaz-Icöz, Sevil, Rapti, Kleopatra, Jungmann, Andreas, Ratte, Antonius, Müller, Oliver J., Karck, Matthias, Seemann, Gunnar, Akin, Ibrahim, Borggrefe, Martin, Zhou, Xiao-Bo, Katus, Hugo A., and Thomas, Dierk

Published
2019
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182. Monitoring Cell-Type–Specific Gene Expression Using Ribosome Profiling In Vivo During Cardiac Hemodynamic Stress

Author

Doroudgar, Shirin, Hofmann, Christoph, Boileau, Etienne, Malone, Brandon, Riechert, Eva, Gorska, Agnieszka A., Jakobi, Tobias, Sandmann, Clara, Jürgensen, Lonny, Kmietczyk, Vivien, Malovrh, Ellen, Burghaus, Jana, Rettel, Mandy, Stein, Frank, Younesi, Fereshteh, Friedrich, Ulrike A., Mauz, Victoria, Backs, Johannes, Kramer, Günter, Katus, Hugo A., Dieterich, Christoph, and Völkers, Mirko

Published
2019
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186. Outcomes Associated With Cardiogenic Shock in Takotsubo Syndrome: Results From the International Takotsubo Registry

Author

Di Vece, Davide, Citro, Rodolfo, Cammann, Victoria L., Kato, Ken, Gili, Sebastiano, Szawan, Konrad A., Micek, Jozef, Jurisic, Stjepan, Ding, Katharina J., Bacchi, Beatrice, Schwyzer, Moritz, Candreva, Alessandro, Bossone, Eduardo, D’Ascenzo, Fabrizio, Sarcon, Annahita, Franke, Jennifer, Napp, L. Christian, Jaguszewski, Milosz, Noutsias, Michel, Münzel, Thomas, Knorr, Maike, Heiner, Susanne, Katus, Hugo A., Burgdorf, Christof, Schunkert, Heribert, Thiele, Holger, Bauersachs, Johann, Tschöpe, Carsten, Pieske, Burkert M., Rajan, Lawrence, Michels, Guido, Pfister, Roman, Cuneo, Alessandro, Jacobshagen, Claudius, Hasenfuβ, Gerd, Karakas, Mahir, Koenig, Wolfgang, Rottbauer, Wolfgang, Said, Samir M., Braun-Dullaeus, Ruediger C., Banning, Adrian, Cuculi, Florim, Kobza, Richard, Fischer, Thomas A., Vasankari, Tuija, Airaksinen, K.E. Juhani, Opolski, Grzegorz, Dworakowski, Rafal, MacCarthy, Philip, Kaiser, Christoph, Osswald, Stefan, Galiuto, Leonarda, Crea, Filippo, Dichtl, Wolfgang, Empen, Klaus, Felix, Stephan B., Delmas, Clément, Lairez, Olivier, El-Battrawy, Ibrahim, Akin, Ibrahim, Borggrefe, Martin, Gilyarova, Ekaterina, Shilova, Alexandra, Gilyarov, Mikhail, Horowitz, John, Kozel, Martin, Tousek, Petr, Widimský, Petr, Winchester, David E., Ukena, Christian, Di Mario, Carlo, Prasad, Abhiram, Böhm, Michael, Bax, Jeroen J., Lüscher, Thomas F., Ruschitzka, Frank, Ghadri, Jelena R., and Templin, Christian

Published
2019
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191. TIP30 counteracts cardiac hypertrophy and failure by inhibiting translational elongation

Author

Grund, Andrea, Szaroszyk, Malgorzata, Korf‐Klingebiel, Mortimer, Malek Mohammadi, Mona, Trogisch, Felix A, Schrameck, Ulrike, Gigina, Anna, Tiedje, Christopher, Gaestel, Matthias, Kraft, Theresia, Hegermann, Jan, Batkai, Sandor, Thum, Thomas, Perrot, Andreas, Remedios, Cris dos, Riechert, Eva, Völkers, Mirko, Doroudgar, Shirin, Jungmann, Andreas, Bauer, Ralf, Yin, Xiaoke, Mayr, Manuel, Wollert, Kai C, Pich, Andreas, Xiao, Hua, Katus, Hugo A, Bauersachs, Johann, Müller, Oliver J, and Heineke, Joerg

Published
2019
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194. ST-segment elevation myocardial infarction

Author

Vogel, Birgit, Claessen, Bimmer E., Arnold, Suzanne V., Chan, Danny, Cohen, David J., Giannitsis, Evangelos, Gibson, C. Michael, Goto, Shinya, Katus, Hugo A., Kerneis, Mathieu, Kimura, Takeshi, Kunadian, Vijay, Pinto, Duane S., Shiomi, Hiroki, Spertus, John A., Steg, P. Gabriel, and Mehran, Roxana

Published
2019
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197. Safety of Stress Cardiac Magnetic Resonance in Patients With Moderate to Severe Aortic Valve Stenosis

Author

Salatzki, Janek, primary, Ochs, Andreas, additional, Kirchgäßner, Nadja, additional, Heins, Jannick, additional, Seitz, Sebastian, additional, Hund, Hauke, additional, Mereles, Derliz, additional, Friedrich, Matthias G., additional, Katus, Hugo A., additional, Frey, Norbert, additional, André, Florian, additional, and Ochs, Marco M., additional

Published
2023
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199. Patients at Intermediate Surgical Risk Undergoing Isolated Interventional or Surgical Aortic Valve Implantation for Severe Symptomatic Aortic Valve Stenosis: One-Year Results From the German Aortic Valve Registry

Author

Werner, Nicolas, Zahn, Ralf, Beckmann, Andreas, Bauer, Timm, Bleiziffer, Sabine, Hamm, Christian W., Berkeredjian, Raffi, Berkowitsch, Alexander, Mohr, Friedrich W., Landwehr, Sandra, Katus, Hugo A., Harringer, Wolfgang, Ensminger, Stephan, Frerker, Christian, Möllmann, Helge, Walther, Thomas, Schneider, Steffen, and Lange, Rüdiger

Published
2018
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