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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. 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
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3. Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID) : A prospective, parallel group, randomised, controlled, open-label trial

Author

Axel Bauer, Michael Schreinlechner, Nikolay Sappler, Theresa Dolejsi, Herbert Tilg, Benedikt A Aulinger, Günter Weiss, Rosa Bellmann-Weiler, Christian Adolf, Dominik Wolf, Markus Pirklbauer, Ivo Graziadei, Hannes Gänzer, Christian von Bary, Andreas E May, Ewald Wöll, Wolfgang von Scheidt, Tienush Rassaf, Daniel Duerschmied, Christoph Brenner, Stefan Kääb, Bernhard Metzler, Michael Joannidis, Hans-Ulrich Kain, Norbert Kaiser, Robert Schwinger, Bernhard Witzenbichler, Hannes Alber, Florian Straube, Niels Hartmann, Stephan Achenbach, Michael von Bergwelt-Baildon, Lukas von Stülpnagel, Sebastian Schoenherr, Lukas Forer, Sabine Embacher-Aichhorn, Ulrich Mansmann, Konstantinos D Rizas, Steffen Massberg, Marcin Bantkowiak, Gabriele Baur, Monika Baylacher, Marcel Beaucamp, Manuel Berger, Lisa Besch, Stefan Brunner, Stephan Budweiser, Heiko Bugger, Raffaele Coletti, Uwe Dorwarth, Jozsef Egresits, Elodie Eiffener, Christian Faul, Armin Finkenstedt, Konstantinos Gatos, Nadine Gauchel, Frank Gindele, Wilhelm Grander, Markus Gunschl, Frank Hartig, Moritz Hecht, Tobias Heer, Lukas Heger, Marcus Hentrich, Lena Horvath, Dritan Keta, Stefan Kiechl, Rudolf Kirchmaier, Andreas Klein, Mathias Klemm, Ewald Kolesnik, Andreas König, Hans Christian Kossmann, Jana Kropacek, Lukas Lanser, Achim Lother, Anja Löw, Amir-Abbas Mahabadi, Stefan Malleier, Gert Mayer, Christoph Müller, Dirk Müller-Wieland, Bernhard Nagel, Hannes Neuwirt, Christoph Olivier, Thomas Raunegger, Martin Reindl, Sebastian Reinstadler, Lisa Riesinger, Michael Schäffner, Johannes Schier, Julia Schock, Peter Schönherr, Martina Schulz, Thomas Schütz, Johannes Schwarz, Johannes Siebermair, Marcus Siry, Anna Spaur, Wolfgang Sturm, Kristin Tessadri, Fabian Theurl, Markus Theurl, Liz Thommes, Christina Tiller, Michael Toifl, Matthias Totzeck, Hedda von zur Mühlen, Nadine Vonderlin, Reza Wakili, Clemens Wendtner, Felix Wenner, Daniela Wimmert-Roidl, and August Zabernigg

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Organ Dysfunction Scores, medicine.medical_treatment, Medizin, Angiotensin-Converting Enzyme Inhibitors, Severity of Illness Index, Corrections, law.invention, Renin-Angiotensin System, 03 medical and health sciences, Angiotensin Receptor Antagonists, 0302 clinical medicine, law, Internal medicine, Severity of illness, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Mechanical ventilation, business.industry, SARS-CoV-2, Organ dysfunction, COVID-19, Articles, Middle Aged, Intensive care unit, Discontinuation, Outcome and Process Assessment, Health Care, 030228 respiratory system, Withholding Treatment, Area Under Curve, Hypertension, SOFA score, Female, Risk Adjustment, Angiotensin-Converting Enzyme 2, medicine.symptom, business
Abstract

Summary Background SARS-CoV-2 entry in human cells depends on angiotensin-converting enzyme 2, which can be upregulated by inhibitors of the renin–angiotensin system (RAS). We aimed to test our hypothesis that discontinuation of chronic treatment with ACE-inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) mitigates the course o\f recent-onset COVID-19. Methods ACEI-COVID was a parallel group, randomised, controlled, open-label trial done at 35 centres in Austria and Germany. Patients aged 18 years and older were enrolled if they presented with recent symptomatic SARS-CoV-2 infection and were chronically treated with ACEIs or ARBs. Patients were randomly assigned 1:1 to discontinuation or continuation of RAS inhibition for 30 days. Primary outcome was the maximum sequential organ failure assessment (SOFA) score within 30 days, where death was scored with the maximum achievable SOFA score. Secondary endpoints were area under the death-adjusted SOFA score (AUCSOFA), mean SOFA score, admission to the intensive care unit, mechanical ventilation, and death. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT04353596. Findings Between April 20, 2020, and Jan 20, 2021, 204 patients (median age 75 years [IQR 66–80], 37% females) were randomly assigned to discontinue (n=104) or continue (n=100) RAS inhibition. Within 30 days, eight (8%) of 104 died in the discontinuation group and 12 (12%) of 100 patients died in the continuation group (p=0·42). There was no significant difference in the primary endpoint between the discontinuation and continuation group (median [IQR] maximum SOFA score 0·00 (0·00–2·00) vs 1·00 (0·00–3·00); p=0·12). Discontinuation was associated with a significantly lower AUCSOFA (0·00 [0·00–9·25] vs 3·50 [0·00–23·50]; p=0·040), mean SOFA score (0·00 [0·00–0·31] vs 0·12 [0·00–0·78]; p=0·040), and 30-day SOFA score (0·00 [10–90th percentile, 0·00–1·20] vs 0·00 [0·00–24·00]; p=0·023). At 30 days, 11 (11%) in the discontinuation group and 23 (23%) in the continuation group had signs of organ dysfunction (SOFA score ≥1) or were dead (p=0·017). There were no significant differences for mechanical ventilation (10 (10%) vs 8 (8%), p=0·87) and admission to intensive care unit (20 [19%] vs 18 [18%], p=0·96) between the discontinuation and continuation group. Interpretation Discontinuation of RAS-inhibition in COVID-19 had no significant effect on the maximum severity of COVID-19 but may lead to a faster and better recovery. The decision to continue or discontinue should be made on an individual basis, considering the risk profile, the indication for RAS inhibition, and the availability of alternative therapies and outpatient monitoring options. Funding Austrian Science Fund and German Center for Cardiovascular Research.

Published
2021

4. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial

Author

Dirk Sibbing, Dániel Aradi, Claudius Jacobshagen, Lisa Gross, Dietmar Trenk, Tobias Geisler, Martin Orban, Martin Hadamitzky, Béla Merkely, Róbert Gábor Kiss, András Komócsi, Csaba A Dézsi, Lesca Holdt, Stephan B Felix, Radoslaw Parma, Mariusz Klopotowski, Robert H G Schwinger, Johannes Rieber, Kurt Huber, Franz-Josef Neumann, Lukasz Koltowski, Julinda Mehilli, Zenon Huczek, Steffen Massberg, Zofia Parma, Maciej Lesiak, Anna Komosa, Michal Kowara, Bartosz Rymuza, Lukasz Malek, Daniel Aradi, Gábor Veress, András Döme Dézsi, Árpád Lux, Judit Papp, Andrea Kovács, Csaba András Dézsi, Sayour Amer, Zoltán Ruzsa, Szilárd Róna, Renáta Ili, Imre Ungi, Ferenc Nagy, Robert Zweiker, Gábor Tóth-Gayor, Paul Haller, Wolfgang von Scheidt, Andreas Blüthgen, Stefan Leggewie, Hans Ulrich Kreider-Stempfle, Thomas Remp, Kaffer Kara, Andreas Mügge, Alexander Wutzler, Stephan Fichtlscherer, Andreas M. Zeiher, Florian Seeger, Martin Hinterseer, Andreas König, Susanne Lederle, Frauke Czepluch, Lars Maier, Wolfgang Schillinger, Samuel Sossalla, Astrid Hummel, Stephan Felix, Mahir Karakas, Karsten Sydow, Tanja Rudolph, Marcel Halbach, Tommaso Gori, Thomas Münzel, Andreas May, Carsten-Manuel Gerstenberg, David Pilecky, Markus Deichstetter, Stefan Kääb, Anja Löw, Matthias Orban, Stefan Sattler, Sabine Deuschl, Daniel Teupser, Harald Mudra, Thomas Räder, Torsten Schütz, Felix Vahldiek, Dimitar Divchev, Hüseyin Ince, Christoph A Nienaber, Henning Radunski, Peter Boekstegers, Jan Horstkotte, Ralf Mueller, Karin Müller, Robert Schwinger, and Oliver Rasp

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, Ticlopidine, Prasugrel, Platelet Function Tests, medicine.medical_treatment, Myocardial Infarction, Hemorrhage, 030204 cardiovascular system & hematology, Drug Administration Schedule, law.invention, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Acute Coronary Syndrome, business.industry, Standard treatment, Percutaneous coronary intervention, General Medicine, Middle Aged, Clopidogrel, medicine.disease, 3. Good health, Surgery, Europe, Stroke, Female, Drug Monitoring, business, Prasugrel Hydrochloride, Ticagrelor, Platelet Aggregation Inhibitors, medicine.drug
Abstract

Summary Background Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT). Methods In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22. Findings Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7%) in the guided de-escalation group and in 118 patients (9%) in the control group (p non-inferiority =0·0004; hazard ratio [HR] 0·81 [95% CI 0·62–1·06], p superiority =0·12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3%]) versus in the control group (42 patients [3%]; p non-inferiority =0·0115). There were 64 BARC 2 or higher bleeding events (5%) in the de-escalation group versus 79 events (6%) in the control group (HR 0·82 [95% CI 0·59–1·13]; p=0·23). Interpretation Guided de-escalation of antiplatelet treatment was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. Our trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI. Funding Klinikum der Universitat Munchen, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.

Published
2017
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6. Editorial

Author

Robert Schwinger and Matthias Pauschinger

Subjects
General Medicine
Published
2017
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7. [Third generation beta-blockers: current state of research on vasodilating beta-blockers]

Author

Dennis, Ladage, Christian, Reidenbach, Albert, Lichtenthal, Robert, Schwinger, and Klara, Brixius

Subjects
Aged, 80 and over, Endothelium-Dependent Relaxing Factors, Metabolic Syndrome, Platelet Aggregation, Research, Vasodilator Agents, Apoptosis, Blood Pressure, Adrenergic beta-Agonists, Nitric Oxide, Lipids, Nebivolol, Mice, Ethanolamines, Hypertension, Animals, Humans, Benzopyrans, Vascular Resistance, Cell Division, Aged, Randomized Controlled Trials as Topic
Abstract

Nebivolol (Nomexor) is a third generation, vasodilating beta-blocker with a high beta(1)-adrenoceptor selectivity. Nebivolol acts as an agonist at the beta(3) adrenoceptor as well as the estrogen receptor thereby releasing nitric oxide in blood vessels via eNOS. Pleiotropic effects of nebivolol furthermore include a positive influence on cholesterol and triglycerides and a decrease in thrombocyte activity. Nebivolol is recommended in the guidelines of the European cardiac society (ESC) for patients with metabolic syndrome. Nebivolol's main properties in combination with its broad range of beneficial pleiotropic effects allow it to be clearly distinguished from other second and third generation beta-blockers.

Published
2008

9. Sarcoplasmic Ca2 release is prolonged in nonfailing myocardium of diabetic patients.

Author

Sabine Grönke, Christian Adam, Maida Ribati, Jan Brabender, Carsten Zobel, Konrad Frank, Jens Wippermann, Robert Schwinger, Klara Brixius, and Jochen Müller-Ehmsen

Abstract

Abstract   Background Asymptomatic diabetic patients have a high incidence of clinically unrecognized left ventricular dysfunction with an abnormal cardiac response to exercise. We, therefore, examined subclinical defects in the contraction–relaxation cycle and intracellular Ca2 regulation in myocardium of asymptomatic type 2 diabetic patients. Methods Alterations in the dynamics of the intracellular Ca2 transient and contractility were recorded in right atrial myocardium of type 2 diabetic patients and non-diabetic control tissue loaded with fura-2. In order to gain an insight into mechanisms underlying the altered Ca2 handling in diabetic myocardium levels of mRNA, protein expression and phosphorylation of key proteins in sarcoplasmic Ca2 handling were determined. Results In isolated atrial trabeculae of diabetic myocardium the rise of systolic Ca2 was significantly prolonged, but relaxation of the Ca2 transient was unaltered compared to control tissue. Accordingly, the levels of expression of mRNA and protein of the Ca2 release channel (RyR2) of the sarcoplasmic reticulum were reduced by 68 and 22%, respectively. Endogenous phosphorylation of RyR2 by protein kinases C, however, was increased by 31% in diabetic myocardium, as assessed by the back-phosphorylation technique. Levels of expression of SERCA2 and phospholamban were unaltered between both groups. Conclusions Intracellular Ca2 release is prolonged in non-failing myocardium of type 2 diabetic patients and this may be primarily due to a decreased expression of RyR2. This defective Ca2 release may represent an early stage of ventricular dysfunction in type 2 diabetes and would favor the abnormal response to exercise frequently observed in asymptomatic diabetic patients. [ABSTRACT FROM AUTHOR]

Published
2008

11. Reduced sarcoplasmic reticulum Ca2+-ATPase activity and dephosphorylated phospholamban contribute to contractile dysfunction in human hibernating myocardium.

Author

Holger Nef, Helge Möllmann, Woitek Skwara, Birgit Bölck, Robert Schwinger, Ch. Hamm, Sawa Kostin, Jutta Schaper, and Albrecht Elsässer

Abstract

Human hibernating myocardium (HHM) is characterized by reversible contractile dysfunction during chronic ischemia. A disturbed calcium-homeostasis is a decisive factor for reduced functional capacity in heart diseases. We therefore investigated calcium-handling proteins in HHM. In 12 patients suffering from multi-vessel coronary artery disease and contractile dysfunction with indication for bypass surgery, HHM was detected preoperatively by thallium scintigraphy, radionuclide ventriculography and dobutamine echocardiography. Transmural biopsies of these regions were taken and analyzed by immunohistochemistry and electron microscopy. Furthermore, SR-calcium ATPase (SERCA2a), phospholamban (PLN), the phosphorylated forms of PLN (PLN-Ser16, PLN-Thr17) as well as sodium-calcium exchanger (NCX) and ryanodine receptor (RyR2) were investigated by RT-PCR and Western-blotting. Additionally, SERCA2a activity was measured by an enzyme-coupled assay. In all patients complete functional recovery could be documented 3 months after revascularization by repeating all preoperative investigations. In HHM maximal SERCA2a activity was significantly reduced (HHM: 424.5± 33.9, control: 609.0± 48.5 nmol ATP mg protein−1 min−1, p≰ 0.05), whereas SERCA2a protein levels were unchanged. mRNA levels (HHM: 1.36± 0.08 vs. control: 0.78± 0.04, p≰ 0.05) and protein amount (HHM:1.67± 0.14 vs. control: 1.00± 0.04, p≰ 0.05) of PLN (A1) were increased resulting in an increased PLN:SERCA2a-ratio. PLN-Ser16 (HHM: 0.60± 0.08 vs. control: 1.00± 0.11, p≰ 0.05) and PLN-Thr17 (HHM: 0.63± 0.11 vs. control: 1.00± 0.06, p≰ 0.05) phosphorylation was significantly decreased. RyR2 and NCX showed no significant alteration. In HHM a decreased activity of SERCA2a due to an impaired phosphorylation of PLN contributes to contractile dysfunction. The increase in the relative ratio of PLN/SERCA2a leads to a decreased calcium affinity of SERCA2a. [ABSTRACT FROM AUTHOR]

Published
2006

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