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1. Telemedical cardiac risk assessment by implantable cardiac monitors in patients after myocardial infarction with autonomic dysfunction (SMART-MI-DZHK9): a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial

Author

Axel Bauer, ProfMD, Nikolay Sappler, MD, Lukas von Stülpnagel, PhD, Mathias Klemm, MD, Michael Schreinlechner, MD, Felix Wenner, MD, Johannes Schier, MD, Amani Al Tawil, MSc, Theresa Dolejsi, MD, Aresa Krasniqi, MD, Elodie Eiffener, MSc, Christa Bongarth, MD, Markus Stühlinger, MD, Martin Huemer, MD, Tommaso Gori, ProfMD, Reza Wakili, ProfMD, Riza Sahin, MD, Robert Schwinger, MD, Matthias Lutz, MD, Armin Luik, MD, Nele Gessler, MD, Peter Clemmensen, ProfMD, Axel Linke, ProfMD, Lars S Maier, ProfMD, Martin Hinterseer, MD, Mathias C Busch, MD, Florian Blaschke, MD, Stefan Sack, ProfMD, Carsten Lennerz, MSc, Manuela Licka, MD, Roland R Tilz, ProfMD, Christian Ukena, MD, Joachim R Ehrlich, ProfMD, Markus Zabel, ProfMD, Georg Schmidt, ProfMD, Ulrich Mansmann, Prof, Stefan Kääb, ProfMD, Konstantinos D Rizas, MD, Steffen Massberg, ProfMD, Andreas May, Peter Seitzer, Roland Schmidt, Dritan Keta, Viktoria Janke, Christian Schläger, Elisabeth André, Niels Brandt, Alexandra Schön, Alfred Zollner, Luisa Freyer, Wolfgang Hamm, Johannes Beil, Anna Katharina Strüven, Anja Loew, Stephanie Fichtner, Philipp Lange, Aresa Krasniqi, Ulrich Grabmeier, Heidi Estner, Philipp Bengel, Lars Lüthje, Aleksandra Kirova, Thomas Fischer, Leonard Bergau, Jonas Herting, Simon Schlögl, Helge Haarmann, Klaudia Schlögl (Illes), Ekrem Uecer, Sabine Sag, Maria Tafelmeier, Carsten Jungbauer, Sabine Fredersdorf-Hahn, Christina Strack, Benedikt Seither, Joachim Seegers, Dominic Millenaar, Jan Wintrich, Patrick Fischer, Axel Buob, Amjad Razouk, Thomas Demming, Johanne Frank, Constantin Kühl, Ulrike Ellendt, Sarah Sandrock, Julia Gänsbacher, Janosch Cupa, Daniel Sinnecker, Karl-Ludwig Laugwitz, Alexander Steger, Anna Berkefeld, Karin Schinke, Petra Barthel, Michael Dommasch, Maiwand Amadei, Gerhard Hindricks, Danilo Obradovic, Michael Döring, Kerstin Bode, Sebastian Hilbert, Susanne Löbe, Helge Knopp, Sebastian König, Silke John, Katharina Schöne, Philipp Hartung, Christian Binner, Christine Meyer-Zürn, Martin Duckheim, Christian Eick, Fabian Simpfle, Jürgen Schreieck, Lars Mizera, Verena Tscholl, Lisa Steinbeck, Nadija Güc, Anne-Sophie Schatz, Philipp Attanasio, Andrea Heuberger, Mattias Roser, Barbara Bellmann, Patrick Nagel, Sebastian Biewener, Saba Suhail, Benjamin Juri, Christian Meyer, Stephan Wiilems, Christiane Jungen, Susanne Schmitt, Paula Münkerer, Julia Vogler, Lukas Kaiser, Benjamin Schäffer, Moritz Nies, Tobias Tönnis, Nina Fluschnik, Hanno Grahn, Christoph Waldeyer, Shinwan Kany, Nils Arne Sörensen, Simon Winkelmann, Özge Akbulak, Nils Arne Gosau, Tilman Würger, Natalie Arnold, Nele Geßler, Alexander Jobs, Paula Münkler, Stefan Rausch, Jelena Köster, Ben Brüggemann, Amr Abdin, Christian Wacker, Philipp Grotherr, Bastian Fries, Maximilian Faust, Stefanie Steuer, Patrick Swojanowsky, Stephan Willems, Nathaniel Portz, Amar Ujeyl, Matthias Krüger, Robert Gramlich, Till Köhler, Armin Sause, Ina Nover, Athanasios-Panagiotis Ziakos, Veaceslav Ciobanu, Norman Spelsberg, Johannes Siebermair, Amir-Abbas Mahabadi, Miriam Köhler, Nadine Vonderlin, Lisa Riesinger, Edison Abdiu, Anja Bachmann, Marie Frenzel, Astrid Hummel, Kristin Lehnert, Anne Krüger, Franke Busse, Andreas Napp, Dirk Müller-Wieland, Simone Battermann, Philipp Lacour, Tobias Trippel, Nick Lasse Beetz, Leonhard Schleußner, Veronika Zach, Christina Rozados, Harald Mudra, Stephan Staubach, Alexander Illmann, Michael Joner, Matthias Bock, Christof Kolb, Tobias Koch, Rebecca Fröhlich, Carsten Lennerz, Tobias Lenz, Patrick Fuchs, Markus Freißmuth, Christian Grebmer, Jürgen Kuschyk, Malte Kranert, Fabian Fastenrath, Gökhan Yücel, Boris Rudic, Sarah Würfel, Albrecht Römer, Andreas Böhmer, Jörg Honold, Stamatis Georgopoulos, Lukas Gleirscher, Susanne Lederle, Artem Chaplygin, Matthias Pauschinger, Andrea Brinker-Paschke, Jana Kropacek, Lars Eckardt, Christian Ellermann, Niklas Bode, Florian Reinke, Hauke Engelke, Robert Höllriegel, Felix Woitek, Ephraim Winzer, Karim Ibrahim, Christian Pflücke, Georg Ende, Uwe Speiser, Stephan Haußig, Rolf Wachter, Tobias Uhe, Torsten Konrad, Edgar Zitron, Jeton Destani, Fangyi Fu, Samer Al Said, Ziya Kaya, Wilfried Schgör, and Thomas Senoner

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Summary: Background: Cardiac autonomic dysfunction after myocardial infarction identifies patients at high risk despite only moderately reduced left ventricular ejection fraction. We aimed to show that telemedical monitoring with implantable cardiac monitors in these patients can improve early detection of subclinical but prognostically relevant arrhythmic events. Methods: We did a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial at 33 centres in Germany and Austria. Survivors of acute myocardial infarction with left ventricular ejection fraction of 36–50% had biosignal analysis for assessment of cardiac autonomic function. Patients with abnormal periodic repolarisation dynamics (≥5·75 deg2) or abnormal deceleration capacity (≤2·5 ms) were randomly assigned (1:1) to telemedical monitoring with implantable cardiac monitors or conventional follow-up. Primary endpoint was time to detection of serious arrhythmic events defined by atrial fibrillation 6 min or longer, atrioventricular block class IIb or higher and fast non-sustained (>187 beats per min; ≥40 beats) or sustained ventricular tachycardia or fibrillation. This study is registered with ClinicalTrials.gov, NCT02594488. Findings: Between May 12, 2016, and July 20, 2020, 1305 individuals were screened and 400 patients at high risk were randomly assigned (median age 64 years [IQR 57–73]); left ventricular ejection fraction 45% [40–48]) to telemedical monitoring with implantable cardiac monitors (implantable cardiac monitor group; n=201) or conventional follow-up (control group; n=199). During median follow-up of 21 months, serious arrhythmic events were detected in 60 (30%) patients of the implantable cardiac monitor group and 12 (6%) patients of the control group (hazard ratio 6·33 [IQR 3·40–11·78]; p

Published
2022
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2. Cardiac Fibrosis Is a Risk Factor for Severe COVID-19

Author

Julian Mustroph, Julian Hupf, Maria J. Baier, Katja Evert, Christoph Brochhausen, Katharina Broeker, Christine Meindl, Benedikt Seither, Carsten Jungbauer, Matthias Evert, Lars S. Maier, and Stefan Wagner

Subjects
SARS-CoV-2, COVID-19, fibrosis, heart, TGF-β1, NRP-1, Immunologic diseases. Allergy, RC581-607
Abstract

Increased left ventricular fibrosis has been reported in patients hospitalized with coronavirus disease 2019 (COVID-19). It is unclear whether this fibrosis is a consequence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection or a risk factor for severe disease progression. We observed increased fibrosis in the left ventricular myocardium of deceased COVID-19 patients, compared with matched controls. We also detected increased mRNA levels of soluble interleukin-1 receptor-like 1 (sIL1-RL1) and transforming growth factor β1 (TGF-β1) in the left ventricular myocardium of deceased COVID-19 patients. Biochemical analysis of blood sampled from patients admitted to the emergency department (ED) with COVID-19 revealed highly elevated levels of TGF-β1 mRNA in these patients compared to controls. Left ventricular strain measured by echocardiography as a marker of pre-existing cardiac fibrosis correlated strongly with blood TGF-β1 mRNA levels and predicted disease severity in COVID-19 patients. In the left ventricular myocardium and lungs of COVID-19 patients, we found increased neuropilin-1 (NRP-1) RNA levels, which correlated strongly with the prevalence of pulmonary SARS-CoV-2 nucleocapsid. Cardiac and pulmonary fibrosis may therefore predispose these patients to increased cellular viral entry in the lung, which may explain the worse clinical outcome observed in our cohort. Our study demonstrates that patients at risk of clinical deterioration can be identified early by echocardiographic strain analysis and quantification of blood TGF-β1 mRNA performed at the time of first medical contact.

Published
2021
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3. Contemporary Management of Severe Symptomatic Aortic Stenosis

Author

Marc Eugène, Piotr Duchnowski, Bernard Prendergast, Olaf Wendler, Cécile Laroche, Jean-Luc Monin, Yannick Jobic, Bogdan A. Popescu, Jeroen J. Bax, Alec Vahanian, Bernard Iung, Jeroen Bax, Michele De Bonis, Victoria Delgado, Michael Haude, Gerhard Hindricks, Aldo P. Maggioni, Luc Pierard, Susanna Price, Raphael Rosenhek, Frank Ruschitzka, Stephan Windecker, Souad Mekhaldi, Katell Lemaitre, Sébastien Authier, Magdy Abdelhamid, Astrid Apor, Gani Bajraktari, Branko Beleslin, Alexander Bogachev-Prokophiev, Daniela Cassar Demarco, Agnes Pasquet, Sait Mesut Dogan, Andrejs Erglis, Arturo Evangelista, Artan Goda, Nikolaj Ihlemann, Huseyin Ince, Andreas Katsaros, Katerina Linhartova, Julia Mascherbauer, Erkin Mirrakhimov, Vaida Mizariene, Shelley Rahman-Haley, Regina Ribeiras, Fuad Samadov, Antti Saraste, Iveta Simkova, Elizabeta Srbinovska Kostovska, Lidia Tomkiewicz-Pajak, Christophe Tribouilloy, Eliverta Zera, Mimoza Metalla, Ervina Shirka, Elona Dado, Loreta Bica, Jorida Aleksi, Gerti Knuti, Lidra Gjyli, Rudina Pjeci, Eritinka Shuperka, Erviola Lleshi, Joana Rustemaj, Marsjon Qordja, Mirald Gina, Senada Husi, Daniel Basic, Regina Steringer-Mascherbauer, Charlotte Huber, Christian Ebner, Elisabeth Sigmund, Andrea Ploechl, Thomas Sturmberger, Veronica Eder, Tanja Koppler, Maria Heger, Andreas Kammerlander, Franz Duca, Christina Binder, Matthias Koschutnik, Leonard Perschy, Lisa Puskas, Chen-Yu Ho, Farid Aliyev, Vugar Guluzada, Galib Imanov, Firdovsi Ibrahimov, Abbasali Abbasaliyev, Tahir Ahmedov, Fargana Muslumova, Jamil Babayev, Yasmin Rustamova, Tofig Jahangirov, Rauf Samadov, Muxtar Museyibov, Elnur Isayev, Oktay Musayev, Shahin Xalilov, Saleh Huseynov, Madina Yuzbashova, Vuqar Zamanov, Vusal Mammadov, Gery Van Camp, Martin Penicka, Hedwig Batjoens, Philippe Debonnaire, Daniel Dendooven, Sebastien Knecht, Mattias Duytschaever, Yves Vandekerckhove, Luc Missault, Luc Muyldermans, René Tavernier, Tineke De Grande, Patrick Coussement, Joyce DeTroyer, Katrien Derycker, Kelly De Jaegher, Antoine Bondue, Christophe Beauloye, Céline Goffinet, Daniela Corina Mirica, Frédéric Vanden Eynden, Philippe Van de Borne, Béatrice Van Frachen, David Vancraeynest, Jean Louis Vanoverschelde, Sophie Pierard, Mihaela Malanca, Florence Sinnaeve, Séverine Tahon, Marie De Clippel, Frederic Gayet, Jacques Loiseau, Nico Van de Veire, Veronique Moerman, Anne-Marie Willems, Bernard Cosyns, Steven Droogmans, Andreea Motoc, Dirk Kerkhove, Daniele Plein, Bram Roosens, Caroline Weytjens, Patrizio Lancellotti, Elena Raluca Dulgheru, Ilona Parenicova, Helena Bedanova, Frantisek Tousek, Stepanka Sindelarova, Julia Canadyova, Milos Taborsky, Jiri Ostransky, null Ivona simkova, Marek Vicha, Libor Jelinek, Irena Opavska, Miroslav Homza, Miriam Kvrayola, Radim Brat, Dan Mrozek, Eva Lichnerova, Iveta Docekalova, Marta Zarybnicka, Marketa Peskova, Patrik Roucka, Vlasta Stastna, Dagmar Jungwirtova Vondrackova, Alfred Hornig, Matus Niznansky, Marian Branny, Alexandra Vodzinska, Miloslav Dorda, Libor Snkouril, Krystyna Kluz, Jana Kypusova, Radka Nezvalova, Niels Thue Olsen, Hosam Hasan Ali, Salma Taha, Mohamed Hassan, Ahmed Afifi, Hamza Kabil, Amr Mady, Hany Ebaid, Yasser Ahmed, Mohammad Nour, Islam Talaat, CairoMaiy El Sayed, Ahmad Elsayed Mostafa, CairoYasser Sadek, CairoSherif Eltobgi, Sameh Bakhoum, Ramy Doss, Mahmoud Sheashea, Abd Allah Elasry, Ahmed Fouad, Mahmoud Baraka, Sameh Samir, Alaa Roshdy, Yasmin AbdelRazek, Mostafa M. Abd Rabou, Ahmed Abobakr, Moemen Moaaz, Mohamed Mokhtar, Mohamed Ashry, Khaled Elkhashab, Haytham Soliman Ghareeb, Mostafa Kamal, Gomaa AbdelRazek, GizaNabil Farag, Giza:Ahmed Elbarbary, Evette Wahib, Ghada Kazamel, Diaa Kamal, Mahmoud Tantawy, Adel Alansary, Mohammed Yahia, Raouf Mahmoud, Tamer El Banna, Mohamed Atef, Gamela Nasr, Salah Ahmed, Ehab E. El Hefny, Islam Saifelyazal, Mostafa Abd El Ghany, Abd El Rahman El Hadary, Ahmed Khairy, Jyri Lommi, Mika Laine, Minna Kylmala, Katja Kankanen, Anu Turpeinen, Juha Hartikainen, Lari Kujanen, Juhani Airaksinen, Tuija Vasankari, Catherine Szymanski, Yohann Bohbot, Mesut Gun, Justine Rousseaux, Loic Biere, Victor Mateus, Martin Audonnet, Jérémy Rautureau, Charles Cornet, Emmanuel Sorbets, BourgesKarine Mear, Adi Issa, Florent Le Ven, Marie-Claire Pouliquen, Martine Gilard, Alice Ohanessian, Ali Farhat, Alina Vlase, Fkhar Said, Caroline Lasgi, Carlos Sanchez, Romain Breil, Marc Peignon, Jean-Philippe Elkaim, Virginie Jan-Blin, Sylvain Ropars BertrandM'Ban, Hélène Bardet, Samuel Sawadogo, Aurélie Muschoot, Dieudonné Tchatchoua, Simon Elhadad, Aline Maubert, Tahar Lazizi, Kais Ourghi, Philippe Bonnet, Clarisse Menager-Gangloff, Sofiene Gafsi, Djidjiga Mansouri, Victor Aboyans, Julien Magne, Elie Martins, Sarah Karm, Dania Mohty, Guillaume Briday, Amandine David, Sylvestre Marechaux, Caroline Le Goffic, Camille Binda, Aymeric Menet, Francois Delelis, Anne Ringlé, Anne-Laure Castel, Ludovic Appert, Domitille Tristram, Camille Trouillet, Yasmine Nacer, Lucas Ngoy, MarseilleGilbert Habib, Franck Thuny, Julie Haentjens, Jennifer Cautela, Cécile Lavoute, Floriane Robin, Pauline Armangau, Ugo Vergeylen, Khalil Sanhadji, Nessim Hamed Abdallah, Hassan Kerzazi, Mariana Perianu, François Plurien, Chaker Oueslati, Mathieu Debauchez, Zannis Konstantinos, Alain Berrebi, Alain Dibie, Emmanuel Lansac, Aurélie Veugeois, Christelle Diakov, Christophe Caussin, Daniel Czitrom, Suzanna Salvi, Nicolas Amabile, Patrice Dervanian, Stéphanie Lejeune, Imane Bagdadi, Yemmi Mokrane, Gilles Rouault, Jerome Abalea, Marion Leledy, Patrice Horen, Erwan Donal, Christian Bosseau, Elise Paven, Elena Galli, Edouard Collette, Jean-Marie Urien, Valentin Bridonneau, Renaud Gervais, Fabrice Bauer, Houzefa Chopra, Arthur Charbonnier, David Attias, Nesrine Dahouathi, Moukda Khounlaboud, Magalie Daudin, Christophe Thebault, Cécile Hamon, Philippe Couffon, Catherine Bellot, Maelle Vomscheid, Anne Bernard, Fanny Dion, Djedjiga Naudin, Mohammed Mouzouri, Mathilde Rudelin, Alain Berenfeld, Thibault Vanzwaelmen, Tarik Alloui, Marija Gjerakaroska Radovikj, Slavica Jordanova, Werner Scholtz, Eva Liberda-Knoke, Melanie Wiemer, Andreas Mugge, Georg Nickenig, Jan-Malte Sinning, Alexander Sedaghat, Matthias Heintzen, Jan Ballof, Daniel Frenk, Rainer Hambrecht, Harm Wienbergen, Annemarie Seidel, Rico Osteresch, Kirsten Kramer, Janna Ziemann, Ramona Schulze, Wolfgang Fehske, Clarissa Eifler, Bahram Wafaisade, Andreas Kuhn, Sören Fischer, Lutz Lichtenberg, Mareike Brunold, Judith Simons, Doris Balling, Thomas Buck, Bjoern Plicht, Wolfgang Schols, Henning Ebelt, Marwan Chamieh, Jelena Anacker, Tienush Rassaf, Alexander Janosi, Alexander Lind, Julia Lortz, Peter Lüdike, Philipp Kahlert, Harald Rittger, Gabriele Eichinger, Britta Kuhls, Stephan B. Felix, Kristin Lehnert, Ann-Louise Pedersen, Marcus Dorr, Klaus Empen, Sabine Kaczmarek, Mathias Busch, Mohammed Baly, Fikret Er, Erkan Duman, Linda Gabriel, Christof Weinbrenner, Johann Bauersachs, Julian Wider, Tibor Kempf, Michael Bohm, Paul-Christian Schulze, C. Tudor Poerner, Sven Möbius-Winkler, Karsten Lenk, Kerstin Heitkamp, Marcus Franz, Sabine Krauspe, Burghard Schumacher, Volker Windmuller, Sarah Kurwitz, Holger Thiele, Thomas Kurz, Roza Meyer-Saraei, Ibrahim Akin, Christian Fastner, Dirk Lossnitzer, Ursula Hoffmann, Martin Borggrefe, Stefan Baumann, Brigitte Kircher, Claudia Foellinger, Heike Dietz, Bernhard Schieffer, Feraydoon Niroomand, Harald Mudra, Lars Maier, Daniele Camboni, Christoph Birner, Kurt Debl, Michael Paulus, Benedikt Seither, Nour Eddine El Mokhtari, Alper Oner, Evren Caglayan, Mohammed Sherif, Seyrani Yucel, Florian Custodis, Robert Schwinger, Marc Vorpahl, Melchior Seyfarth, Ina Nover, Till Koehler, Sarah Christiani, David Calvo Sanchez, Barbel Schanze, Holger Sigusch, Athir Salman, Jane Hancock, John Chambers, Camelia Demetrescue, Claire Prendergast, Miles Dalby, Robert Smith, Paula Rogers, Cheryl Riley, Dimitris Tousoulis, Ioannis Kanakakis, Konstantinos Spargias, Konstantinos Lampropoulos, Tolis Panagiotis, Athanasios Koutsoukis, Lampros Michalis, Ioannis Goudevenos, Vasileios Bellos, Michail Papafaklis, Lampros Lakkas, George Hahalis, Athanasios Makris, Haralampos Karvounis, Vasileios Kamperidis, Vlasis Ninios, Vasileios Sachpekidis, Pavlos Rouskas, Leonidas Poulimenos, Georgios Charalampidis, Eftihia Hamodraka, Athanasios Manolis, Robert Gabor Kiss, Tunde Borsanyi, Zoltan Jarai, Andras Zsary, Elektra Bartha, Annamaria Kosztin, Alexandra Doronina, Attila Kovacs, Barabas Janos Imre, Chun Chao, Kalman Benke, Istvan Karoczkai, Kati Keltai, Zsolt Förchécz, Zoltán Pozsonyi, Zsigmond Jenei, Adam Patthy, Laszlo Sallai, Zsuzsanna Majoros, Tamás Pál, Jusztina Bencze, Ildiko Sagi, Andrea Molnar, Anita Kurczina, Gabor Kolodzey, Istvan Edes, Valeria Szatmari, Zsuzsanna Zajacz, Attila Cziraki, Adam Nemeth, Reka Faludi, Laszlone Vegh, Eva Jebelovszki, Geza Karoly Lupkovics, Zsofia Kovacs, Andras Horvath, Gezim Berisha, Pranvera Ibrahimi, Luan Percuku, Rano Arapova, Elmira Laahunova, Kseniia Neronova, Zarema Zhakypova, Gulira Naizabekova, Gulnazik Muratova, Iveta Sime, Nikolajs Sorokins, Ginta Kamzola, Irina Cgojeva-Sproge, Gita Rancane, Ramune Valentinaviciene, Laima Rudiene, Rasa Raugaliene, Aiste Bardzilauske, Regina Jonkaitiene, Jurate Petrauskaite, Monika Bieseviciene, Raimonda Verseckaite, Ruta Zvirblyte, Danute Kalibatiene, Greta Radauskaite, Gabija Janaviciute-Matuzeviciene, Dovile Jancauskaite, Deimile Balkute, Juste Maneikyte, Ingrida Mileryte, Monika Vaisvilaite, Lina Gedvilaite, Mykolas Biliukas, Vaiva Karpaviciene, Robert George Xuereb, Elton Pllaha, Roxana Djaberi, Klaudiusz Komor, Agnieszka Gorgon-Komor, Beata Loranc, Jaroslaw Myszor, Katarzyna Mizia-Stec, Adrianna Berger-Kucza, Magdalena Mizia, Mateusz Polak, Piotr Bogacki, Piotr Podolec, Monika Komar, Ewa Sedziwy, Dorota Sliwiak, Bartosz Sobien, Beata Rog, Marta Hlawaty, Urszula Gancarczyk, Natasza Libiszewska, Danuta Sorysz, Andrzej Gackowski, Malgorzata Cieply, Agnieszka Misiuda, Franciszek Racibor, Anna Nytko, Kazimierz Widenka, Maciej Kolowca, Janusz Bak, Andrzej Curzytek, Mateusz Regulski, Malgorzata Kamela, Mateusz Wisniowski, Tomasz Hryniewiecki, Piotr Szymanski, Monika Rozewicz, Maciej Grabowski, Andrzej Budaj, Beata Zaborska, Ewa Pilichowska-Paskiet, Malgorzata Sikora-Frac, Tomasz Slomski, Isabel Joao, Ines Cruz, Hélder Pereira, Rita Cale, Ana Marques, Ana Rita Pereira, Carlos Morais, Antonio Freitas, David Roque, Nuno Antunes, Antonio Costeira Pereira, Catarina Vieira, Nuno Salome, Juliana Martins, Isabel Campos, Goncalo Cardoso, Claudia Silva, Afonso Oliveira, Mariana Goncalves, Rui Martins, Nuno Quintal, Bruno Mendes, Joseline Silva, Joao Ferreira, James Milner, Patricia Alves, Vera Marinho, Paula Gago, Jose Amado, Joao Bispo, Dina Bento, Inocencia Machado, Margarida Oliveira, Lucy Calvo, Pedro von Hate, Bebiana Faria, Ana Galrinho, Luisa Branco, Antonio Goncalves, Tiago Mendonca, Mafalda Selas, Filipe Macedo, Carla Sousa, Sofia Cabral, Filomena Oliveira, Maria Trepa, Marta Fontes-Oliveira, Alzira Nunes, Paulo Araújo, Vasco Gama Ribeiro, Joao Almeida, Alberto Rodrigues, Pedro Braga, Sonia Dias, Sofia Carvalho, Catarina Ferreira, Alberto Ferreira, Pedro Mateus, Miguel Moz, Silvia Leao, Renato Margato, Ilidio Moreira, Jose Guimanaes, Joana Ribeiro, Fernando Goncalves, Jose Cabral, Ines Almeida, Luisa Goncalves, Mariana Tarusi, Calin Pop, Claudia Matei, Diana Tint, Sanziana Barbulescu, Sorin Micu, Ioana Pop, Costica Baba, Doina Dimulescu, Maria Dorobantu, Carmen Ginghina, Roxana Onut, Andreea Popescu, Brandusa Zamfirescu, Raluca Aflorii, Mihaela Popescu, Liviu Ghilencea, Andreeea Rachieru, Monica Stoian, Nicoleta Oprescu, Silvia Iancovici, Iona Petre, Anca Doina Mateescu, Andreea Calin, Simona Botezatu, Roxana Enache, Monica Rosca, Daniela Ciuperca, Evelyn Babalac, Ruxandra Beyer, Laura Cadis, Raluca Rancea, Raluca Tomoaia, Adela Rosianu, Emese Kovacs, Constantin Militaru, Alina Craciun, Oana Mirea, Mihaela Florescu, Lucica Grigorica, Daniela Dragusin, Luiza Nechita, Mihai Marinescu, Teodor Chiscaneanu, Lucia Botezatu, Costela Corciova, Antoniu Octavian Petris, Catalina Arsenescu-Georgescu, Delia Salaru, Dan Mihai Alexandrescu, Carmjen Plesoianu, Ana Tanasa, Ovidiu Mitu, Irina Iuliana Costache, Ionut Tudorancea, Catalin Usurelu, Gabriela Eminovici, Ioan Manitiu, Oana Stoia, Adriana Mitre, Dan-Octavian Nistor, Anca Maier, Silvia Lupu, Mihaela Opris, Adina Ionac, Irina Popescu, Simina Crisan, Cristian Mornos, Flavia Goanta, Liana Gruescu, Oana Voinescu, Madalina Petcu, Ramona Cozlac, Elena Damrina, Liliya Khilova, Irina Ryazantseva, Dmitry Kozmin, Maria Kiseleva, Marina Goncharova, Kamila Kitalaeva, Victoria Demetskay, Artem Verevetinov, Mikhail Fomenko, Elena Skripkina, Viktor Tsoi, Georgii Antipov, Yuri Schneider, Denis Yazikov, Marina Makarova, Aleksei Cherkes, Natalya Ermakova, Aleksandr Medvedev, Anastasia Sarosek, Mikhail Isayan, Tatyana Voronova, Oleg Kulumbegov, Alina Tuchina, Sergei Stefanov, Margarita Klimova, Konstantin Smolyaninov, Zhargalma Dandarova, Victoriya Magamet, Natalia Spiropulos, Sergey Boldyrev, Kirill Barbukhatty, Dmitrii Buyankov, Vladimir Yurin, Yuriy Gross, Maksim Boronin, Mariya Mikhaleva, Mariya Shablovskaya, Alex Zotov, Daniil Borisov, Vasily Tereshchenko, Ekaterina Zubova, A. Kuzmin, Ivan Tarasenko, Alishir Gamzaev, Natalya Borovkova, Tatyana Koroleva, Svetlana Botova, Ilya Pochinka, Vera Dunaeva, Victoria Teplitskaya, Elena I. Semenova, Olga V. Korabel'Nikova, Denis S. Simonov, Elena Denisenko, Natalia Harina, Natalia Yarohno, Svetlana Alekseeva, Julia Abydenkova, Lyubov Shabalkina, Olga Mayorova, Valeriy Tsechanovich, Igor Medvedev, Michail Lepilin, PenzaEvgenii Nemchenko, Vadim Karnahin, Vasilya Safina, Yaroslav Slastin, Venera Gilfanova, Roman Gorbunov, Ramis Jakubov, Aigul Fazylova, Mansur Poteev, Laysan Vazetdinova, Indira Tarasova, Rishat Irgaliyev, Olga Moiseeva, Mikhail Gordeev, Olga Irtyuga, Raisa Moiseeva, Nina Ostanina, Dmitry Zverev, Patimat Murtazalieva, Dmitry Kuznetsov, Mariya Skurativa, Larisa Polyaeva, Kirill Mihaiilov, Biljana Obrenovic-Kircanski, Svetozar Putnik, Dragan Simic, Milan Petrovic, Natasa Markovic Nikolic, Ljiljana Jovovic, Dimitra Kalimanovska Ostric, Milan Brajovic, Milica Dekleva Manojlovic, Vladimir Novakovic, Danijela Zamaklar-Trifunovic, Bojana Orbovic, Olga Petrovic, Marija Boricic-Kostic, Kristina Andjelkovic, Marko Milanov, Maja Despotovic-Nikolic, Sreten Budisavljevic, Sanja Veljkovic, Nataša Cvetinovic, Daniijela Lepojevic, Aleksandra Todorovic, Aleksandra Nikolic, Branislava Borzanovic, Ljiljana Trkulja, Slobodan Tomic, Milan Vukovic, Jelica Milosavljevic, Mirjana Milanovic, Vladan Stakic, Aleksandra Cvetkovic, Suzana Milutinovic, Olivera Bozic, Miodrag Miladinovic, Zoran Nikolic, Dinka Despotovic, Dimitrije Jovanovic, Anastazija Stojsic-Milosavljevic, Aleksandra Ilic, Mirjana Sladojevic, Stamenko Susak, Srdjan Maletin, Salvo Pavlovic, Vladimir Kuzmanovic, Nikola Ivanovic, Jovana Dejanovic, Dusan Ruzicic, Dragana Drajic, Danijel Cvetanovic, Marija Mirkovic, Jon Omoran, Roman Margoczy, Katarina Sedminova, Adriana Reptova, Eva Baranova, Tatiana Valkovicova, Gabriel Valocik, Marian Kurecko, Marianna Vachalcova, Alzbeta Kollarova, Martin Studencan, Daniel Alusik, Marek Kozlej, Jana Macakova, Sergio Moral, Merce Cladellas, Daniele Luiso, Alicia Calvo, Jordi Palet, Juli Carballo, Gisela Teixido Tura, Giuliana Maldonado, Laura Gutierrez, Teresa Gonzalez-Alujas, Rodriguez Palomares Jose Fernando, Nicolas Villalva, Ma Jose Molina-Mora, Ramon Rubio Paton, Juan Jose Martinez Diaz, Pablo Ramos Ruiz, Alfonso Valle, Ana Rodriguez, Edgardo Alania, Emilio Galcera, Julia Seller, Gonzalo de la Morena Valenzuela, Daniel Saura Espin, Dolores Espinosa Garcia, Maria Jose Oliva Sandoval, Josefa Gonzalez, Miguel Garcia Navarro, Maria Teresa Perez-Martinez, Jose Ramon Ortega Trujillo, Irene Menduina Gallego, Daniel San Roman, Eliu David Perez Nogales, Olga Medina, Rodolfo Antonio Montiel Quintero, Pablo Felipe Bujanda Morun, Marta Lopez Perez, Jimmy Plasencia Huaripata, Juan Jose Morales Gonzalez, Veronica Quevedo Nelson, Jose Luis Zamorano, Ariana Gonzalez Gomez, Alfonso Fraile, Maria Teresa Alberca, Joaquin Alonso Martin, Covadonga Fernandez-Golfin, Javier Ramos, Sergio Hernandez Jimenez, Cristina Mitroi, Pedro L. Sanchez Fernandez, Elena Diaz-Pelaez, Beatriz Garde, Luis Caballero, Fermin Martinez Garcia, Francisco Cambronero, Noelia Castro, Antonio Castro, Alejandro De La Rosa, Pastora Gallego, Irene Mendez, David Villagomez Villegas, Manuel Gonzalez Correa, Roman Calvo, Francisco Florian, Rafael Paya, Esther Esteban, Francisco Buendia, Andrés Cubillos, Carmen Fernandez, Juan Pablo Cárdenas, José Leandro Pérez-Boscá, Joan Vano, Joaquina Belchi, Cristina Iglesia-Carreno, Francisco Calvo Iglesias, Aida Escudero-Gonzalez, Sergio Zapateria-Lucea, Juan Sterling Duarte, Lara Perez-Davila, Rafael Cobas-Paz, Rosario Besada-Montenegro, Maribel Fontao-Romeo, Elena Lopez-Rodriguez, Emilio Paredes-Galan, Berenice Caneiro-Queija, Alba Guitian Gonzalez, Abdi Bozkurt, Serafettin Demir, Durmus Unlu, Caglar Emre Cagliyan, Muslum Firat Ikikardes, Mustafa Tangalay, Osman Kuloglu, Necla Ozer, Ugur Canpolat, Melek Didem Kemaloglu, Abdullah Orhan Demirtas, Didar Elif Akgün, Eyup Avci, Gokay Taylan, Mustafa Adem Yilmaztepe, Fatih Mehmet Ucar, Servet Altay, Muhammet Gurdogan, Naile Eris Gudul, Mujdat Aktas, Mutlu Buyuklu, Husnu Degirmenci, Mehmet Salih Turan, Kadir Ugur Mert, Gurbet Ozge Mert, Muhammet Dural, Sukru Arslan, Nurten Sayar, Batur Kanar, Beste Ozben Sadic, Ahmet Anil Sahin, Ahmet Buyuk, Onur Kilicarslan, Cem Bostan, Tarik Yildirim, Seda Elcim Yildirim, Kahraman Cosansu, Perihan Varim, Ersin Ilguz, Recep Demirbag, Asuman Yesilay, Abdullah Cirit, Eyyup Tusun, Emre Erkus, Muhammet Rasit Sayin, Zeynep Kazaz, Selim Kul, Turgut Karabag, Belma Kalayci, Clinical sciences, Cardio-vascular diseases, and Cardiology

Subjects
Male, medicine.medical_specialty, Multivariate analysis, Clinical Decision-Making, Risk Assessment, Severity of Illness Index, decision making, surgery, Risk Factors, Internal medicine, Intervention (counseling), medicine, Clinical endpoint, Humans, 03.02. Klinikai orvostan, guidelines, Symptomatic aortic stenosis, Aged, Retrospective Studies, Aged, 80 and over, business.industry, valvular heart disease, Disease Management, aortic stenosis, Aortic Valve Stenosis, Odds ratio, medicine.disease, Europe, Stenosis, Treatment Outcome, Echocardiography, Aortic Valve, Charlson comorbidity index, transcatheter aortic valve replacement, Female, Morbidity, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies, surgical aortic valve replacement
Abstract

BACKGROUND There were gaps between guidelines and practice when surgery was the only treatment for aortic stenosis (AS). OBJECTIVES This study analyzed the decision to intervene in patients with severe AS in the EORP VHD (EURObservational Research Programme Valvular Heart Disease) II survey. METHODS Among 2,152 patients with severe AS, 1,271 patients with high-gradient AS who were symptomatic fulfilled a Class I recommendation for intervention according to the 2012 European Society of Cardiology guidelines; the primary end point was the decision for intervention. RESULTS A decision not to intervene was taken in 262 patients (20.6%). In multivariate analysis, the decision not to intervene was associated with older age (odds ratio [OR]: 1.34 per 10-year increase; 95% CI: 1.11 to 1.61; P = 0.002), New York Heart Association functional classes I and II versus III (OR: 1.63; 95% CI: 1.16 to 2.30; P = 0.005), higher age adjusted Charlson comorbidity index (OR: 1.09 per 1-point increase; 95% CI: 1.01 to 1.17; P = 0.03), and a lower transaortic mean gradient (OR: 0.81 per 10-mm Hg decrease; 95% CI: 0.71 to 0.92; P < 0.001). During the study period, 346 patients (40.2%, median age 84 years, median EuroSCORE II [European System for Cardiac Operative Risk Evaluation II] 3.1%) underwent transcatheter intervention and 515 (59.8%, median age 69 years, median EuroSCORE II 1.5%) underwent surgery. A decision not to intervene versus intervention was associated with lower 6-month survival (87.4%; 95% CI: 82.0 to 91.3 vs 94.6%; 95% CI: 92.8 to 95.9; P < 0.001). CONCLUSIONS A decision not to intervene was taken in 1 in 5 patients with severe symptomatic AS despite a Class I recommendation for intervention and the decision was particularly associated with older age and combined comorbidities. Transcatheter intervention was extensively used in octogenarians. (J Am Coll Cardiol 2021;78:2131-2143) (c) 2021 by the American College of Cardiology Foundation.

Published
2021

4. Cardiac Fibrosis Is a Risk Factor for Severe COVID-19

Author

Katharina A.E. Broeker, Lars S. Maier, Julian Mustroph, Benedikt Seither, Christine Meindl, Stefan Wagner, Julian Hupf, Matthias Evert, Maria J. Baier, Carsten Jungbauer, Katja Evert, and Christoph Brochhausen

Subjects
Adult, Male, Risk, medicine.medical_specialty, Cardiac fibrosis, Heart Ventricles, Pulmonary Fibrosis, Immunology, 610 Medizin, heart, Severity of Illness Index, Transforming Growth Factor beta1, Fibrosis, Internal medicine, TGF-β1, Pulmonary fibrosis, medicine, Immunology and Allergy, NRP-1, Humans, 570 Biowissenschaften, Biologie, Risk factor, Original Research, Aged, ddc:610, Lung, business.industry, SARS-CoV-2, Myocardium, fibrosis, COVID-19, Emergency department, RC581-607, Middle Aged, Viral Load, medicine.disease, Interleukin-1 Receptor-Like 1 Protein, Neuropilin-1, medicine.anatomical_structure, Cohort, Cardiology, Female, ddc:570, Immunologic diseases. Allergy, business, SARS-CoV-2, COVID-19, fibrosis, heart, TGF-b1, NRP-1, Transforming growth factor
Abstract

Increased left ventricular fibrosis has been reported in patients hospitalized with coronavirus disease 2019 (COVID-19). It is unclear whether this fibrosis is a consequence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection or a risk factor for severe disease progression. We observed increased fibrosis in the left ventricular myocardium of deceased COVID-19 patients, compared with matched controls. We also detected increased mRNA levels of soluble interleukin-1 receptor-like 1 (sIL1-RL1) and transforming growth factor β1 (TGF-β1) in the left ventricular myocardium of deceased COVID-19 patients. Biochemical analysis of blood sampled from patients admitted to the emergency department (ED) with COVID-19 revealed highly elevated levels of TGF-β1 mRNA in these patients compared to controls. Left ventricular strain measured by echocardiography as a marker of pre-existing cardiac fibrosis correlated strongly with blood TGF-β1 mRNA levels and predicted disease severity in COVID-19 patients. In the left ventricular myocardium and lungs of COVID-19 patients, we found increased neuropilin-1 (NRP-1) RNA levels, which correlated strongly with the prevalence of pulmonary SARS-CoV-2 nucleocapsid. Cardiac and pulmonary fibrosis may therefore predispose these patients to increased cellular viral entry in the lung, which may explain the worse clinical outcome observed in our cohort. Our study demonstrates that patients at risk of clinical deterioration can be identified early by echocardiographic strain analysis and quantification of blood TGF-β1 mRNA performed at the time of first medical contact.

Published
2021
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