103 results on '"A. Katus Hugo"'
Search Results
2. Epigenetic regulation of cardiac electrophysiology in atrial fibrillation: HDAC2 determines action potential duration and suppresses NRSF in cardiomyocytes
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Lugenbiel, Patrick, Govorov, Katharina, Syren, Pascal, Rahm, Ann-Kathrin, Wieder, Teresa, Wunsch, Maximilian, Weiberg, Nadine, Manolova, Emili, Gramlich, Dominik, Rivinius, Rasmus, Finke, Daniel, Lehmann, Lorenz H., Schweizer, Patrick A., Frank, Derk, El Tahry, Fadwa A., Bruehl, Claus, Heimberger, Tanja, Sandke, Steffi, Weis, Tanja, Most, Patrick, Schmack, Bastian, Ruhparwar, Arjang, Karck, Matthias, Frey, Norbert, Katus, Hugo A., and Thomas, Dierk
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- 2021
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3. Pulmonary vein isolation treats symptomatic AF in a patient with Lamin A/C mutation: case report and review of the literature
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Rahm, Ann-Kathrin, Lugenbiel, Patrick, Ochs, Marco, Meder, Benjamin, Thomas, Dierk, Katus, Hugo A., and Scholz, Eberhard
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- 2020
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4. Atrial Fibrillation
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Rahm, Ann-Kathrin, Katus, Hugo A., Thomas, Dierk, Hecker, Markus, Editor-in-Chief, Backs, Johannes, Series Editor, Freichel, Marc, Series Editor, Korff, Thomas, Series Editor, Thomas, Dierk, Series Editor, and Remme, Carol Ann, editor
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- 2018
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5. NOAC monotherapy in patients with concomitant indications for oral anticoagulation undergoing transcatheter aortic valve implantation
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Geis, Nicolas A., Kiriakou, Christina, Chorianopoulos, Emmanuel, Uhlmann, Lorenz, Katus, Hugo A., and Bekeredjian, Raffi
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- 2018
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6. Atrial fibrillation and heart failure-associated remodeling of two-pore-domain potassium (K2P) channels in murine disease models: focus on TASK-1
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Wiedmann, Felix, Schulte, Jan S., Gomes, Bruna, Zafeiriou, Maria-Patapia, Ratte, Antonius, Rathjens, Franziska, Fehrmann, Edda, Scholz, Beatrix, Voigt, Niels, Müller, Frank Ulrich, Thomas, Dierk, Katus, Hugo A., and Schmidt, Constanze
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- 2018
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7. TREK-1 (K2P2.1) K+ channels are suppressed in patients with atrial fibrillation and heart failure and provide therapeutic targets for rhythm control
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Lugenbiel, Patrick, Wenz, Fabian, Syren, Pascal, Geschwill, Pascal, Govorov, Katharina, Seyler, Claudia, Frank, Derk, Schweizer, Patrick A., Franke, Jennifer, Weis, Tanja, Bruehl, Claus, Schmack, Bastian, Ruhparwar, Arjang, Karck, Matthias, Frey, Norbert, Katus, Hugo A., and Thomas, Dierk
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- 2016
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8. Coding and non-coding variants in the SHOX2 gene in patients with early-onset atrial fibrillation
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Hoffmann, Sandra, Clauss, Sebastian, Berger, Ina M., Weiß, Birgit, Montalbano, Antonino, Röth, Ralph, Bucher, Madeline, Klier, Ina, Wakili, Reza, Seitz, Hervé, Schulze-Bahr, Eric, Katus, Hugo A., Flachsbart, Friederike, Nebel, Almut, Guenther, Sabina PW., Bagaev, Erik, Rottbauer, Wolfgang, Kääb, Stefan, Just, Steffen, and Rappold, Gudrun A.
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- 2016
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9. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS):The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC
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Hindricks, Gerhard, Potpara, Tatjana, Dagres, Nikolaos, Arbelo, Elena, Bax , Jeroen J., Blomstro¨m-Lundqvist, Carina, Boriani, Giuseppe, Castella, Manuel, Dan, Gheorghe-Andrei, Dilaveris, Polychronis E., Fauchier, Laurent, Filippatos, Gerasimos, Kalman, Jonathan M., Meir, Mark La, Lane, Deirdre A, Lebeau, Jean-Pierre, Lettino, Maddalena, Lip, Gregory Y H, Pinto, Fausto J, Thomas, G Neil, Valgimigli, Marco, Gelder, Isabelle C Van, Putte, Bart P Van, Watkins, Caroline L, Kirchhof, Paulus, Kühne, Michael, Aboyans, Victor, Ahlsson, Anders, Balsam, Pawel, Bauersachs, Johann, Benussi, Stefano, Brandes, Axel, Braunschweig, Frieder, Camm, A John, Capodanno, Davide, Casadei, Barbara, Conen, David, Crijns, Harry J G M, Delgado, Victoria, Dobrev, Dobromir, Drexel, Heinz, Eckardt, Lars, Fitzsimons, Donna, Folliguet, Thierry, Gale, Chris P., Gorenek, Bulent, Haeusler, Karl Georg, Heidbuchel, Hein, Iung, Bernard, Katus, Hugo A, Kotecha, Dipak, Landmesser, Ulf, Leclercq, Christophe, Lewis, Basil S, Mascherbauer, Julia, Merino, Jose Luis, Merkely, Béla, Mont, Lluis, Mueller, Christian, Nagy, Klaudia V., Oldgren, Jonas, Pavlovic, Nikola, Pedretti, Roberto F.E., Petersen, Steffen Ellebæk, Piccini, Jonathan P, Popescu, Bogdan A, Pürerfellner, Helmut, Richter, Dimitrios J., Roffi, Marco, Rubboli, Andrea, Scherr, Daniel, Schnabel, Renate B, Simpson, Iain, Shlyakhto, Evgeny, Sinner, Moritz F, Steffel, Jan, Sousa-Uva, Miguel, Suwalski, Piotr, Svetlosak, Martin, and Touyz, Rhian M.
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rhythm control ,left atrial ablation ,left atrial appendage occlusion ,AF surgery ,non-vitamin K antagonist oral anticoagulants ,screening ,Cardiology ,Anticoagulants ,Thoracic Surgery ,Guidelines ,upstream therapy ,stroke ,Europe ,vitamin K antagonists ,cardioversion ,antiarrhythmic drugs ,recommendations ,catheter ablation ,Atrial Fibrillation/diagnosis ,Humans ,atrial fibrillation ,ABC pathway ,anticoagulation ,pulmonary vein isolation ,rate control - Published
- 2021
10. Novel electrophysiological properties of dronedarone: inhibition of human cardiac two-pore-domain potassium (K2P) channels
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Schmidt, Constanze, Wiedmann, Felix, Schweizer, Patrick A., Becker, Rüdiger, Katus, Hugo A., and Thomas, Dierk
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- 2012
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11. Genetic suppression of Gαs protein provides rate control in atrial fibrillation
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Lugenbiel, Patrick, Thomas, Dierk, Kelemen, Kamilla, Trappe, Kerstin, Bikou, Olympia, Schweizer, Patrick A., Voss, Frederik, Becker, Rüdiger, Katus, Hugo A., and Bauer, Alexander
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- 2012
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12. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS) : the Task Force for the diagnosis and management of atrialfibrillation of the European Society of Cardiology (ESC) : developed with the special contribution of the European HeartRhythm Association (EHRA) of the ESC
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Hindricks, Gerhard, Potpara, Tatjana, Dagres, Nikolaos, Arbelo, Elena, Bax, Jeroen J., Blomström-Lundqvist, Carina, Boriani, Giuseppe, Castella, Manuel, Dan, Gheorghe-Andrei, Dilaveris, Polychronis E., Fauchier, Laurent, Petersen, Steffen E., Piccini, Jonathan P., Popescu, Bogdan A., Pürerfellner, Helmut, Richter, Dimitrios J., Roffi, Marco, Rubboli, Andrea, Scherr, Daniel, Schnabel, Renate B., Simpson, Iain A., Raatikainen, Pekka, Shlyakhto, Evgeny, Sinner, Moritz F., Steffel, Jan, Suwalski, Piotr, Svetlosak, Martin, Touyz, Rhian M., Windecker, Stephan, Baigent, Colin, Collet, Jean-Philippe, Dean, Veronica, Boveda, Serge, Fitzsimons, Donna, Gale, Chris P., Grobbee, Diederick E., Halvorsen, Sigrun, Lung, Bernard, Jüni, Peter, Petronio, Anna Sonia, Sousa Uva, Miguel, Delassi, Tahar, Sisakian, Hamayak S., Papiashvili, Giorgi, Chasnoits, Alexandr, De Pauw, Michel, Smajić, Elnur, Shalganov, Tchavdar, Avraamides, Panayiotis, Kautzner, Josef, Gerdes, Christian, Alaziz, Ahmad Abd, Kampus, Priit, Vassilikos, Vassilios P., Csanádi, Zoltán, Arnar, David O., Galvin, Joseph, Barsheshet, Alon, Caldarola, Pasquale, Rakisheva, Amina, Filippatos, Gerasimos, Bytyçi, Ibadete, Kerimkulova, Alina, Kalejs, Oskars, Njeim, Mario, Puodziukynas, Aras, Groben, Laurent, Sammut, Mark A., Grosu, Aurel, Boskovic, Aneta, Moustaghfir, Abdelhamid, Kalman, Jonathan M., de Groot, Natasja, Poposka, Lidija, Anfinsen, Ole-Gunnar, Mitkowski, Przemyslaw P., Cavaco, Diogo, Siliste, Calin, Mikhaylov, Evgeny N., Bertelli, Luca, Kojic, Dejan, Hatala, Robert, La Meir, Mark, Fras, Zlatko, Arribas, Fernando, Juhlin, Tord, Sticherling, Christian, Abid, Leila, Atar, Ilyas, Sychov, Oleg, Bates, Matthew G. D., Zakirov, Nodir U., Lane, Deirdre A., Lebeau, Jean-Pierre, Lettino, Maddalena, Lip, Gregory Y. H., Pinto, Fausto J., Thomas, G. Neil, Valgimigli, Marco, Van Gelder, Isabelle C., Van Putte, Bart P., Watkins, Caroline L., Kirchhof, Paulus, Kühne, Michael, Aboyans, Victor, Ahlsson, Anders, Balsam, Pawel, Bauersachs, Johann, Benussi, Stefano, Brandes, Axel, Braunschweig, Frieder, Camm, A. John, Capodanno, Davide, Casadei, Barbara, Conen, David, Crijns, Harry J. G. M., Delgado, Victoria, Dobrev, Dobromir, Drexel, Heinz, Eckardt, Lars, Folliguet, Thierry, Gorenek, Bulent, Haeusler, Karl Georg, Heidbuchel, Hein, Iung, Bernard, Katus, Hugo A., Kotecha, Dipak, Landmesser, Ulf, Leclercq, Christophe, Lewis, Basil S., Mascherbauer, Julia, Merino, Jose Luis, Merkely, Béla, Mont, Lluís, Mueller, Christian, Nagy, Klaudia V., Oldgren, Jonas, Pavlović, Nikola, Pedretti, Roberto F. E., and Repositório da Universidade de Lisboa
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Rate control ,AF surgery ,Guidelines ,Upstream therapy ,Recommendations ,Left atrial appendage occlusion ,Atrial fibrillation ,Pulmonary vein isolation ,Left atrial ablation ,Antiarrhythmic drugs ,Cardioversion ,Stroke ,Anticoagulation ,Vitamin K antagonists ,Screening ,Non-vitamin K antagonist oral anticoagulants ,Rhythm control ,Catheter ablation ,ABC pathway - Abstract
© 2020 European Society of Cardiology. All rights reserved., Atrial fibrillation (AF) poses significant burden to patients, physicians, and healthcare systems globally. Substantial research efforts and resources are being directed towards gaining detailed information about the mechanisms underlying AF, its natural course and effective treatments (see also the ESC Textbook of Cardiovascular Medicine: CardioMed) and new evidence is continuously generated and published. The complexity of AF requires a multifaceted, holistic, and multidisciplinary approach to the management of AF patients, with their active involvement in partnership with clinicians. Streamlining the care of patients with AF in daily clinical practice is a challenging but essential requirement for effective management of AF. In recent years, substantial progress has been made in the detection of AF and its management, and new evidence is timely integrated in this third edition of the ESC guidelines on AF. The 2016 ESC AF Guidelines introduced the concept of the five domains to facilitate an integrated structured approach to AF care and promote consistent, guideline-adherent management for all patients. The Atrial Fibrillation Better Care (ABC) approach in the 2020 ESC AF Guidelines is a continuum of this approach, with the goal to further improve the structured management of AF patients, promote patient values, and finally improve patient outcomes.
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- 2020
13. COPD in patients after heart transplantation is associated with a prolonged hospital stay, early posttransplant atrial fibrillation, and impaired posttransplant survival
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Rivinius,Rasmus, Helmschrott,Matthias, Ruhparwar,Arjang, Schmack,Bastian, Darche,Fabrice F., Thomas,Dierk, Bruckner,Tom, Katus,Hugo A., Ehlermann,Philipp, and Doesch,Andreas
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spirometry ,COPD ,Clinical Epidemiology ,atrial fibrillation ,Tiffeneau index ,heart transplantation ,mortality ,Original Research - Abstract
Rasmus Rivinius,1 Matthias Helmschrott,1 Arjang Ruhparwar,2 Bastian Schmack,2 Fabrice F Darche,1 Dierk Thomas,1 Tom Bruckner,3 Hugo A Katus,1 Philipp Ehlermann,1,* Andreas O Doesch1,4,* 1Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany; 2Department of Cardiac Surgery, Heidelberg University Hospital, Heidelberg, Germany; 3Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany; 4Department of Pneumology and Oncology, Asklepios Hospital, Bad Salzungen, Germany *These authors contributed equally to this work Objectives: COPD is associated with reduced physical activity, an increased risk for pulmonary infections, and impaired survival in nontransplant patients. The aim of this study was to investigate the influence of COPD in patients after heart transplantation (HTX). Methods: We performed an observational retrospective single-center study of 259 patients receiving HTX at Heidelberg University Hospital between 2003 and 2012. Patients were stratified by the Tiffeneau index (forced expiratory volume in 1 second/forced vital capacity [FEV1/FVC])
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- 2018
14. Antiarrhythmic Properties of Ranolazine: Inhibition of Atrial Fibrillation Associated TASK-1 Potassium Channels
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Ratte, Antonius, Wiedmann, Felix, Kraft, Manuel, Katus, Hugo A., and Schmidt, Constanze
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Pharmacology ,antiarrhythmic drugs ,atrial fibrillation ,Pharmacology (medical) ,ranolazine ,TASK-1 ,KCNK3 ,K2P3.1 ,Original Research - Abstract
Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and one of the major causes of cardiovascular morbidity and mortality. Despite good progress within the past years, safe and effective treatment of AF remains an unmet clinical need. The anti-anginal agent ranolazine has been shown to exhibit antiarrhythmic properties via mainly late INa and IKr blockade. This results in prolongation of the atrial action potential duration (APD) and effective refractory period (ERP) with lower effect on ventricular electrophysiology. Furthermore, ranolazine has been shown to be effective in the treatment of AF. TASK-1 is a two-pore domain potassium (K2P) channel that shows nearly atrial specific expression within the human heart and has been found to be upregulated in AF, resulting in shortening the atrial APD in patients suffering from AF. We hypothesized that inhibition TASK-1 contributes to the observed electrophysiological and clinical effects of ranolazine. Methods: We used Xenopus laevis oocytes and CHO-cells as heterologous expression systems for the study of TASK-1 inhibition by ranolazine and molecular drug docking simulations to investigate the ranolazine binding site and binding characteristics. Results: Ranolazine acts as an inhibitor of TASK-1 potassium channels that inhibits TASK-1 currents with an IC50 of 30.6 ± 3.7 µM in mammalian cells and 198.4 ± 1.1 µM in X. laevis oocytes. TASK-1 inhibition by ranolazine is not frequency dependent but shows voltage dependency with a higher inhibitory potency at more depolarized membrane potentials. Ranolazine binds within the central cavity of the TASK-1 inner pore, at the bottom of the selectivity filter. Conclusions: In this study, we show that ranolazine inhibits TASK-1 channels. We suggest that inhibition of TASK-1 may contribute to the observed antiarrhythmic effects of Ranolazine. This puts forward ranolazine as a prototype drug for the treatment of atrial arrhythmia because of its combined efficacy on atrial electrophysiology and lower risk for ventricular side effects.
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- 2019
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15. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS)
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Hindricks, Gerhard, Potpara, Tatjana, Dagres, Nikolaos, Arbelo, Elena, Bax, Jeroen J, Blomström-Lundqvist, Carina, Boriani, Giuseppe, Castella, Manuel, Dan, Gheorghe-Andrei, Dilaveris, Polychronis E, Fauchier, Laurent, Filippatos, Gerasimos, Kalman, Jonathan M, La Meir, Mark, Lane, Deirdre A, Lebeau, Jean-Pierre, Lettino, Maddalena, Lip, Gregory Y H, Pinto, Fausto J, Thomas, G Neil, Valgimigli, Marco, Van Gelder, Isabelle C, Van Putte, Bart P, Watkins, Caroline L, Kirchhof, Paulus, Kühne, Michael, Aboyans, Victor, Ahlsson, Anders, Balsam, Pawel, Bauersachs, Johann, Benussi, Stefano, Brandes, Axel, Braunschweig, Frieder, Camm, A John, Capodanno, Davide, Casadei, Barbara, Conen, David, Crijns, Harry J G M, Delgado, Victoria, Dobrev, Dobromir, Drexel, Heinz, Eckardt, Lars, Fitzsimons, Donna, Folliguet, Thierry, Gale, Chris P, Gorenek, Bulent, Haeusler, Karl Georg, Heidbuchel, Hein, Iung, Bernard, Katus, Hugo A, Kotecha, Dipak, Landmesser, Ulf, Leclercq, Christophe, Lewis, Basil S, Mascherbauer, Julia, Merino, Jose Luis, Merkely, Béla, Mont, Lluís, Mueller, Christian, Nagy, Klaudia V, Oldgren, Jonas, Pavlović, Nikola, Pedretti, Roberto F E, Petersen, Steffen E, Piccini, Jonathan P, Popescu, Bogdan A, Pürerfellner, Helmut, Richter, Dimitrios J, Roffi, Marco, Rubboli, Andrea, Scherr, Daniel, Schnabel, Renate B, Simpson, Iain A, Shlyakhto, Evgeny, Sinner, Moritz F, Steffel, Jan, Sousa-Uva, Miguel, Suwalski, Piotr, Svetlosak, Martin, Touyz, Rhian M, Neil Thomas, G, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Cardiovascular Centre (CVC), Surgical clinical sciences, and Cardiac Surgery
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left atrial ablation ,left atrial appendage occlusion ,AF surgery ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Management of atrial fibrillation ,030204 cardiovascular system & hematology ,Cardioversion ,VITAMIN-K ANTAGONIST ,surgery ,chemistry.chemical_compound ,0302 clinical medicine ,cardioversion ,Edoxaban ,QUALITY-OF-LIFE ,antiarrhythmic drugs ,OBSTRUCTIVE SLEEP-APNEA ,catheter ablation ,RADIOFREQUENCY CATHETER ABLATION ,Medicine ,atrial fibrillation ,030212 general & internal medicine ,anticoagulation ,reproductive and urinary physiology ,ComputingMilieux_MISCELLANEOUS ,pulmonary vein isolation ,0303 health sciences ,rhythm control ,EACTS ,HEART RHYTHM SOCIETY ,recommendations ,Atrial fibrillation ,General Medicine ,non-Vitamin K antagonist oral anticoagulants ,Vitamin K antagonist ,PULMONARY-VEIN ISOLATION ,stroke ,3. Good health ,2020 ESC Guidelines ,Dronedarone ,vitamin K antagonists ,Cardiothoracic surgery ,Cardio-Thoracic Surgery ,embryonic structures ,DIRECT ORAL ANTICOAGULANTS ,cardiovascular system ,Cardiology ,Dose reduction ,biological phenomena, cell phenomena, and immunity ,Cardiology and Cardiovascular Medicine ,medicine.drug ,Quinidine ,medicine.medical_specialty ,medicine.drug_class ,non-vitamin K antagonist oral anticoagulants ,PERCUTANEOUS CORONARY INTERVENTION ,Renal function ,macromolecular substances ,ABC pathway ,Guidelines ,rate control ,screening ,upstream therapy ,Vitamin K antagonists ,B700 ,03 medical and health sciences ,Internal medicine ,Diseases of the circulatory (Cardiovascular) system ,cardiovascular diseases ,030304 developmental biology ,urogenital system ,business.industry ,medicine.disease ,TRANSIENT ISCHEMIC ATTACK ,ANTIARRHYTHMIC-DRUG-THERAPY ,chemistry ,030228 respiratory system ,Concomitant ,RC666-701 ,business - Abstract
Supplementary Table 9, column 'Edoxaban', row 'eGFR category', '95 mL/min' (page 15). The cell should be coloured green instead of yellow. It should also read "60 mg"instead of "60 mg (use with caution in 'supranormal' renal function)."In the above-indicated cell, a footnote has also been added to state: "Edoxaban should be used in patients with high creatinine clearance only after a careful evaluation of the individual thromboembolic and bleeding risk."Supplementary Table 9, column 'Edoxaban', row 'Dose reduction in selected patients' (page 16). The cell should read "Edoxaban 60 mg reduced to 30 mg once daily if any of the following: creatinine clearance 15-50 mL/min, body weight
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- 2021
16. The impact of Wilson disease on myocardial tissue and function: a cardiovascular magnetic resonance study.
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Salatzki, Janek, Mohr, Isabelle, Heins, Jannick, Cerci, Mert H., Ochs, Andreas, Paul, Oliver, Riffel, Johannes, André, Florian, Hirschberg, Kristóf, Müller-Hennessen, Matthias, Giannitsis, Evangelos, Friedrich, Matthias G., Merle, Uta, Weiss, Karl Heinz, Katus, Hugo A., and Ochs, Marco
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MYOCARDIUM ,CARDIOMYOPATHIES ,LEFT ventricular dysfunction ,MAGNETIC resonance imaging ,ATRIAL fibrillation ,DESCRIPTIVE statistics ,HEPATOLENTICULAR degeneration ,HEART failure ,DISEASE risk factors - Abstract
Background: Systemic effects of altered serum copper processing in Wilson Disease (WD) might induce myocardial copper deposition and consequently myocardial dysfunction and structural remodeling. This study sought to investigate the prevalence, manifestation and predictors of myocardial tissue abnormalities in WD patients. Methods: We prospectively enrolled WD patients and an age-matched group of healthy individuals. We applied cardiovascular magnetic resonance (CMR) to analyze myocardial function, strain, and tissue characteristics. A subgroup analysis of WD patients with predominant neurological (WD-neuro
+ ) or hepatic manifestation only (WD-neuro− ) was performed. Results: Seventy-six patients (37 years (27–49), 47% women) with known WD and 76 age-matched healthy control subjects were studied. The prevalence of atrial fibrillation in WD patients was 5% and the prevalence of symptomatic heart failure was 2.6%. Compared to healthy controls, patients with WD had a reduced left ventricular global circumferential strain (LV-GCS), and also showed abnormalities consistent with global and regional myocardial fibrosis. WD-neuro+ patients presented with more severe structural remodeling and functional impairment when compared to WD-neuro− patients. Conclusions: In a large cohort, WD was not linked to a distinct cardiac phenotype except CMR indexes of myocardial fibrosis. More research is warranted to assess the prognostic implications of these findings. Trial registration: This trial is registered at the local institutional ethics committee (S-188/2018). [ABSTRACT FROM AUTHOR]- Published
- 2021
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17. Differential regulation of KCa2.1 (KCNN1) K+ channel expression by histone deacetylases in atrial fibrillation with concomitant heart failure.
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Rahm, Ann‐Kathrin, Wieder, Teresa, Gramlich, Dominik, Müller, Mara Elena, Wunsch, Maximilian N., El Tahry, Fadwa A., Heimberger, Tanja, Sandke, Steffi, Weis, Tanja, Most, Patrick, Katus, Hugo A., Thomas, Dierk, and Lugenbiel, Patrick
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HEART failure ,ATRIAL fibrillation ,VENTRICULAR remodeling ,DEACETYLASES ,HISTONE deacetylase ,CARDIAC patients - Abstract
Atrial fibrillation (AF) with concomitant heart failure (HF) poses a significant therapeutic challenge. Mechanism‐based approaches may optimize AF therapy. Small‐conductance, calcium‐activated K+ (KCa, KCNN) channels contribute to cardiac action potential repolarization. KCNN1 exhibits predominant atrial expression and is downregulated in chronic AF patients with preserved cardiac function. Epigenetic regulation is suggested by AF suppression following histone deacetylase (HDAC) inhibition. We hypothesized that HDAC‐dependent KCNN1 remodeling contributes to arrhythmogenesis in AF complicated by HF. The aim of this study was to assess KCNN1 and HDAC1–7 and 9 transcript levels in AF/HF patients and in a pig model of atrial tachypacing‐induced AF with reduced left ventricular function. In HL‐1 atrial myocytes, tachypacing and anti‐Hdac siRNAs were employed to investigate effects on Kcnn1 mRNA levels. KCNN1 expression displayed side‐specific remodeling in AF/HF patients with upregulation in left and suppression in right atrium. In pigs, KCNN1 remodeling showed intermediate phenotypes. HDAC levels were differentially altered in humans and pigs, reflecting highly variable epigenetic regulation. Tachypacing recapitulated downregulation of Hdacs1, 3, 4, 6, and 7 with a tendency towards reduced Kcnn1 levels in vitro, indicating that atrial high rates induce remodeling. Finally, Kcnn1 expression was decreased by knockdown of Hdacs2, 3, 6, and 7 and enhanced by genetic Hdac9 inactivation, while anti‐Hdac1, 4, and 5 siRNAs did not affect Kcnn1 transcript levels. In conclusion, KCNN1 and HDAC expression is differentially remodeled in AF complicated by HF. Direct regulation of KCNN1 by HDACs in atrial myocytes provides a basis for mechanism‐based antiarrhythmic therapy. [ABSTRACT FROM AUTHOR]
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- 2021
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18. Trigger-Specific Remodeling of KCa2 Potassium Channels in Models of Atrial Fibrillation.
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Rahm, Ann-Kathrin, Gramlich, Dominik, Wieder, Teresa, Müller, Mara Elena, Schoeffel, Axel, Tahry, Fadwa A El, Most, Patrick, Heimberger, Tanja, Sandke, Steffi, Weis, Tanja, Ullrich, Nina D, Korff, Thomas, Lugenbiel, Patrick, Katus, Hugo A, and Thomas, Dierk
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POTASSIUM channels ,HEART failure ,ATRIAL fibrillation ,CARDIAC pacing ,TACHYCARDIA ,HYPOXEMIA ,CALCIUM ,MUSCLE cells - Abstract
Aim: Effective antiarrhythmic treatment of atrial fibrillation (AF) constitutes a major challenge, in particular, when concomitant heart failure (HF) is present. HF-associated atrial arrhythmogenesis is distinctly characterized by prolonged atrial refractoriness. Small-conductance, calcium-activated K
+ (KCa , SK, KCNN) channels contribute to cardiac action potential repolarization and are implicated in AF susceptibility and therapy. The mechanistic impact of AF/HF-related triggers on atrial KCa channels is not known. We hypothesized that tachycardia, stretch, β-adrenergic stimulation, and hypoxia differentially determine KCa 2.1– 2.3 channel remodeling in atrial cells. Methods: KCNN1-3 transcript levels were assessed in AF/HF patients and in a pig model of atrial tachypacing-induced AF with reduced left ventricular function. HL-1 atrial myocytes were subjected to proarrhythmic triggers to investigate the effects on Kcnn mRNA and KCa channel protein. Results: Atrial KCNN1-3 expression was reduced in AF/HF patients. KCNN2 and KCNN3 suppression was recapitulated in the corresponding pig model. In contrast to human AF, KCNN1 remained unchanged in pigs. Channel- and stressor-specific remodeling was revealed in vitro. Lower expression levels of KCNN1/KCa 2.1 were linked to stretch and β-adrenergic stimulation. Furthermore, KCNN3/KCa 2.3 expression was suppressed upon tachypacing and hypoxia. Finally, KCNN2/KCa 2.2 abundance was specifically enhanced by hypoxia. Conclusion: Reduction of KCa 2.1– 2.3 channel expression might contribute to the action potential prolongation in AF complicated by HF. Subtype-specific KCa 2 channel remodeling induced by tachypacing, stretch, β-adrenergic stimulation, or hypoxia is expected to differentially determine atrial remodeling, depending on patient-specific activation of each triggering factor. Stressor-dependent KCa 2 regulation in atrial myocytes provides a starting point for mechanism-based antiarrhythmic therapy. [ABSTRACT FROM AUTHOR]- Published
- 2021
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19. Prevalence and relevance of impaired left ventricular function in chronic moderate regurgitation of native aortic valves.
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Gomes, Bruna, Hees, Katharina, Hund, Hauke, Mereles, Derliz, Meder, Benjamin, Katus, Hugo A., and Bekeredjian, Raffi
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AORTIC valve insufficiency ,CARDIOMYOPATHIES ,DISEASE progression ,LEFT heart ventricle diseases ,KIDNEY failure ,ATRIAL fibrillation - Abstract
Background: Reduced ejection fraction (EF) in chronic moderate aortic regurgitation (AR) could be either due to a late remodelling response after longstanding moderate AR, or could represent a specific phenotype of cardiomyopathy (CMP) with concomitant AR. The aim of this study was to analyse progression of left ventricular (LV) impairment in moderate AR. Methods: All patients in our echocardiography database between 2005 and 2016 were screened to identify pure chronic moderate AR, excluding significant coronary artery disease (CAD) or concomitant valve disease. Remaining 152 patients were divided into three groups: (a) preserved systolic LV function; (b) reduced LV EF and prediagnosed concomitant cardiomyopathy (CMP); (c) reduced LV EF without prediagnosed CMP. Results: The majority patients (group A = 66%) had preserved systolic LV function, remaining oligosymptomatic with stable LVEDD at follow-up. Non-CMP patients with reduced EF at baseline (group C = 18%) were significantly older (group C: 74 vs. group A: 61 years, p <.001) whereas left ventricular end-diastolic diameter (LVEDD) significantly increased over time (p =.046). Development of renal insufficiency, atrial fibrillation and NYHA > II were significant risk factors linked to the worsening of LV function in patients with moderate AR. Conclusion: Preserved LV EF and LVEDD remain stable over a long lasting period in the majority of patients. However, these data suggest that some patients develop reduced LV EF, even without progression of AR to severe, especially if renal insufficiency or atrial fibrillation are present. [ABSTRACT FROM AUTHOR]
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- 2020
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20. Comparison of posttransplant outcomes in patients with no, acute, or chronic amiodarone use before heart transplantation
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Rivinius, Rasmus, Helmschrott, Matthias, Ruhparwar, Arjang, Darche, Fabrice F, Thomas, Dierk, Bruckner, Tom, Katus, Hugo A, and Doesch, Andreas O
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Adult ,Male ,Pacemaker, Artificial ,Drug Design, Development and Therapy ,Amiodarone ,Stroke Volume ,Middle Aged ,heart transplantation ,bradycardia ,survival ,pacemaker ,Treatment Outcome ,Heart Rate ,Atrial Fibrillation ,Humans ,Female ,Postoperative Period ,Anti-Arrhythmia Agents ,Original Research ,Aged ,Follow-Up Studies ,Retrospective Studies - Abstract
Rasmus Rivinius,1 Matthias Helmschrott,1 Arjang Ruhparwar,2 Fabrice F Darche,1 Dierk Thomas,1 Tom Bruckner,3 Hugo A Katus,1 Andreas O Doesch1 1Department of Cardiology, Angiology and Pneumology, 2Department of Cardiac Surgery, Heidelberg University Hospital, 3Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany Background: Major concerns about the safety of pretransplant amiodarone use have been raised. As a result of its long half-life, the cardiac allograft is exposed to amiodarone posing potential risks such as bradycardia, requirement for pacemaker implantation, or increased mortality after heart transplantation (HTX).Objective: The aim of this study is to investigate the posttransplant outcomes of patients with no, acute, or chronic amiodarone use before HTX.Methods: This retrospective single-center study included 530 adult patients who received HTX between 06/1989 and 12/2012. Patients were stratified by their amiodarone therapy before HTX: no continuous amiodarone use (≤90 days before HTX), acute amiodarone use (≤90 days before HTX), and chronic amiodarone use (>90 days before HTX). Differences between the 3 groups in demographics, posttransplant medication, echocardiographic features, heart rates including occurrences of bradycardia, permanent pacemaker implantation, atrial fibrillation (AF), and survival were analyzed.Results: A total of 412 patients (77.7%) were in the “no amiodarone” group, 23 patients (4.4%) in the “acute amiodarone” group, and 95 patients (17.9%) in the “chronic amiodarone” group. Left ventricular ejection fraction (P=0.5819), heart rates including occurrence of bradycardia during posttransplant week 1 (P=0.0979 and P=0.2695), week 2 (P=0.1214 and P=0.8644), week 3 (P=0.1033 and P=0.8894), and week 4 (P=0.2892 and P=0.8644), permanent pacemaker implantation within 30-day (P=0.8644), or overall follow-up after HTX (P=0.8664) were not significant between groups. Patients with chronic pretransplant amiodarone therapy had the lowest rate of early posttransplant AF (P=0.0065). There was no statistically significant difference between groups in 30-day (P=0.8656), 1-year (P=1.0000), 2-year (P=0.8763), 5-year (P=0.5174), or overall posttransplant follow-up mortality (P=0.1936).Conclusion: Administration of acute or chronic pretransplant amiodarone was not related to an increased occurrence of bradycardia, requirement for permanent pacemaker implantation, or mortality after HTX. Importantly, chronic amiodarone use effectively reduced early AF after HTX, whereas acute amiodarone use showed no such effect. Keywords: amiodarone, atrial fibrillation, bradycardia, heart transplantation, pacemaker, survival
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- 2017
21. Electrophysiological effects of non-vitamin K antagonist oral anticoagulants on atrial repolarizing potassium channels.
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Wiedmann, Felix, Schlund, Daniel, Kraft, Manuel, Nietfeld, Jendrik, Katus, Hugo A, Schmidt, Constanze, and Thomas, Dierk
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ATRIAL fibrillation diagnosis ,PYRIDINE ,RESEARCH ,STROKE ,ORAL drug administration ,RESEARCH methodology ,ATRIAL fibrillation ,POTASSIUM ,ANTICOAGULANTS ,MEDICAL cooperation ,EVALUATION research ,COMPARATIVE studies - Abstract
Aims: Non-vitamin K antagonist oral anticoagulants (NOACs) are widely used in the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF). The efficacy of NOACs has been attributed in part to pleiotropic effects that are mediated through effects on thrombin, factor Xa, and their respective receptors. Direct pharmacological effects of NOACs and cardiac ion channels have not been addressed to date. We hypothesized that the favourable clinical outcome of NOAC use may be associated with previously unrecognized effects on atrial repolarizing potassium channels.Methods and Results: This study was designed to elucidate acute pharmacological effects of NOACs on cloned ion channels Kv11.1, Kv1.5, Kv4.3, Kir2.1, Kir2.2, and K2P2.1 contributing to IKr, IKur, Ito, IK1, and IK2P K+ currents. Human genes, KCNH2, KCNA5, KCND3, KCNJ2, KCNJ12, and KCNK2, were heterologously expressed in Xenopus laevis oocytes, and currents were recorded using voltage-clamp electrophysiology. Apixaban, dabigatran, edoxaban, and rivaroxaban applied at 1 µM did not significantly affect peak current amplitudes of Kv11.1, Kv1.5, Kv4.3, Kir2.1, Kir2.2, or K2P2.1 K+ channels. Furthermore, biophysical characterization did not reveal significant effects of NOACs on current-voltage relationships of study channels.Conclusion: Apixaban, dabigatran, edoxaban, and rivaroxaban did not exhibit direct functional interactions with human atrial K+ channels underlying IKr, IKur, Ito, IK1, and IK2P currents that could account for beneficial clinical outcome associated with the drugs. Indirect or chronic effects and potential underlying signalling mechanisms remain to be investigated. [ABSTRACT FROM AUTHOR]- Published
- 2020
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22. Elevated pre‐transplant pulmonary vascular resistance is associated with early post‐transplant atrial fibrillation and mortality.
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Rivinius, Rasmus, Helmschrott, Matthias, Ruhparwar, Arjang, Schmack, Bastian, Darche, Fabrice F., Thomas, Dierk, Bruckner, Tom, Doesch, Andreas O., Katus, Hugo A., and Ehlermann, Philipp
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ATRIAL fibrillation ,HEART transplantation ,MORTALITY ,LENGTH of stay in hospitals ,HEART transplantation complications - Abstract
Aims: Severely elevated pre‐transplant pulmonary vascular resistance (PVR) has been linked to adverse effects after heart transplantation (HTX). The impact of a moderately increased PVR before HTX on post‐transplant outcomes remains uncertain. The aim of this study was to investigate the effects of an elevated pre‐transplant PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units) on outcomes after HTX. Methods and results: This observational retrospective single‐centre study included 561 patients receiving HTX at Heidelberg Heart Center between 1989 and 2015. Patients were stratified by degree of pre‐transplant PVR. Analyses covered demographics, post‐transplant medication, mortality and causes of death after HTX, early post‐transplant atrial fibrillation (AF), and length of the initial hospital stay after HTX. Ninety‐four patients (16.8%) had a PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units). These patients had a higher rate of early post‐transplant AF [20.2 vs. 10.7%, difference: 9.5%, 95% confidence interval (CI): 0.9–18.1%, P = 0.01] and an increased 30 day post‐transplant mortality (25.5 vs. 6.4%, hazard ratio: 4.4, 95% CI: 2.6–7.6, P < 0.01), along with a higher percentage of death due to transplant failure (21.2 vs. 4.1%, difference: 17.1%, 95% CI: 8.7–25.5%, P < 0.01). Multivariate analysis revealed a PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units) as a significant risk factor for increased 30 day mortality after HTX (hazard ratio: 4.4, 95% CI: 2.5–7.6, P < 0.01). Kaplan–Meier estimator showed a lower 2 year survival after HTX (P < 0.01) in patients with a PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units). Conclusions: Elevated pre‐transplant PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units) is associated with early post‐transplant AF and increased mortality after HTX. [ABSTRACT FROM AUTHOR]
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- 2020
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23. The Management of Atrial Fibrillation with Oral Anticoagulant Drugs.
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Zeymer, Uwe, Schneider, Steffen, Hochadel, Matthias, Kleemann, Thomas, Borggrefe, Martin, Akin, Ibrahim, Katus, Hugo, Thomas, Dierk, Werdan, Karl, and Senges, Jochen
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ATRIAL fibrillation ,PATIENT compliance ,ATRIAL fibrillation treatment ,ORAL medication ,ANTICOAGULANTS ,METROPOLITAN areas - Abstract
The article discusses research which analyzed guideline adherence with respect to overtreatment or undertreatment of atrial fibrillation (AF) with oral anticoagulant (OAC) drugs in the metropolitan region Rhine-Neckar, Germany. Topics include brief information on the ARENA project, overview of the study subjects, details of the research findings and indication of good guideline adherence regarding OAC treatment in AF.
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- 2023
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24. The SAMe-TT2R2 score and quality of anticoagulation in atrial fibrillation:a simple aid to decision-making on who is suitable (or not) for vitamin K antagonists
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Ding, Wern Yew, Potpara, Tatjana, Blomström‐lundqvist, Carina, Boriani, Giuseppe, Marin, Francisco, Fauchier, Laurent, Lip, Gregory, Lip, G.Y.H., Tavazzi, L., Maggioni, A., Dan, G‐a., Nabauer, M., Kalarus, Z., Goda, A., Mairesse, G., Shalganov, T., Antoniades, L., Taborsky, M., Riahi, S., Muda, P., García Bolao, I., Piot, O., Etsadashvili, K., Simantirakis, E., Haim, M., Azhari, A., Najafian, J., Santini, M., Mirrakhimov, E., Kulzida, K.A, Erglis, A., Poposka, L., Burg, M., Crijns, H., Erküner, Ö., Atar, D., Lenarczyk, R., Martins Oliveira, M., Shah, D., Serdechnaya, E., Diker, E., Lane, D., Zëra, E., Ekmekçiu, U., Paparisto, V., Tase, M., Gjergo, H., Dragoti, J., Ciutea, M., Ahadi, N., Husseini, Z. El, Raepers, M., Leroy, J., Haushan, P., Jourdan, A., Lepiece, C., Desteghe, L., Vijgen, J., Koopman, P., Genechten, G., Heidbuchel, H., Boussy, T., Coninck, M., Eeckhoutte, H., Bouckaert, N., Friart, A., Boreux, J., Arend, C., Evrard, P., Stefan, L., Hoffer, E., Herzet, J., Massoz, M., Celentano, C., Sprynger, M., Pierard, L., Melon, P., Hauwaert, B., Kuppens, C., Faes, D., Lier, D., Dorpe, A., Gerardy, A., Deceuninck, O., Xhaet, O., Dormal, F., Ballant, E., Blommaert, D., Yakova, D., Hristov, M., Yncheva, T., Stancheva, N., Tisheva, S., Tokmakova, M., Nikolov, F., Gencheva, D., Kunev, B., Stoyanov, M., Marchov, D., Gelev, V., Traykov, V., Kisheva, A., Tsvyatkov, H., Shtereva, R., Bakalska‐georgieva, S., Slavcheva, S., Yotov, Y., Kubíčková, M., Marni Joensen, A., Gammelmark, A., Hvilsted Rasmussen, L., Dinesen, P., Krogh Venø, S., Sorensen, B., Korsgaard, A., Andersen, K., Fragtrup Hellum, C., Svenningsen, A., Nyvad, O., Wiggers, P., May, O., Aarup, A., Graversen, B., Jensen, L., Andersen, M., Svejgaard, M., Vester, S., Hansen, S., Lynggaard, V., Ciudad, M., Vettus, R., Maestre, A., Castaño, S., Cheggour, S., Poulard, J., Mouquet, V., Leparrée, S., Bouet, J., Taieb, J., Doucy, A., Duquenne, H., Furber, A., Dupuis, J., Rautureau, J., Font, M., Damiano, P., Lacrimini, M., Abalea, J., Boismal, S., Menez, T., Mansourati, J., Range, G., Gorka, H., Laure, C., Vassalière, C., Elbaz, N., Lellouche, N., Djouadi, K., Roubille, F., Dietz, D., Davy, J., Granier, M., Winum, P., Leperchois‐jacquey, C., Kassim, H., Marijon, E., Le Heuzey, J., Fedida, J., Maupain, C., Himbert, C., Gandjbakhch, E., Hidden‐lucet, F., Duthoit, G., Badenco, N., Chastre, T., Waintraub, X., Oudihat, M., Lacoste, J., Stephan, C., Bader, H., Delarche, N., Giry, L., Arnaud, D., Lopez, C., Boury, F., Brunello, I., Lefèvre, M., Mingam, R., Haissaguerre, M., Le Bidan, M., Pavin, D., Le Moal, V., Leclercq, C., Beitar, T., Martel, I., Schmid, A., Sadki, N., Romeyer‐bouchard, C., da Costa, A., Arnault, I., Boyer, M., Piat, C., Lozance, N., Nastevska, S., Doneva, A., Fortomaroska Milevska, B., Sheshoski, B., Petroska, K., Taneska, N., Bakrecheski, N., Lazarovska, K., Jovevska, S., Ristovski, V., Antovski, A., Lazarova, E., Kotlar, I., Taleski, J., Kedev, S., Zlatanovik, N., Jordanova, S., Bajraktarova Proseva, T., Doncovska, S., Maisuradze, D., Esakia, A., Sagirashvili, E., Lartsuliani, K., Natelashvili, N., Gumberidze, N., Gvenetadze, R., Gotonelia, N., Kuridze, N., Papiashvili, G., Menabde, I., Glöggler, S., Napp, A., Lebherz, C., Romero, H., Schmitz, K., Berger, M., Zink, M., Köster, S., Sachse, J., Vonderhagen, E., Soiron, G., Mischke, K., Reith, R., Schneider, M., Rieker, W., Boscher, D., Taschareck, A., Beer, A., Oster, D., Ritter, O., Adamczewski, J., Walter, S., Frommhold, A., Luckner, E., Richter, J., Schellner, M., Landgraf, S., Bartholome, S., Naumann, R., Schoeler, J., Westermeier, D., William, F., Wilhelm, K., Maerkl, M., Oekinghaus, R., Denart, M., Kriete, M., Tebbe, U., Scheibner, T., Gruber, M., Gerlach, A., Beckendorf, C., Anneken, L., Arnold, M., Lengerer, S., Bal, Z., Uecker, C., Förtsch, H., Fechner, S., Mages, V., Martens, E., Methe, H., Schmidt, T., Schaeffer, B., Hoffmann, B., Moser, J., Heitmann, K., Willems, S., Klaus, C., Lange, I., Durak, M., Esen, E., Mibach, F., Mibach, H., Utech, A., Gabelmann, M., Stumm, R., Ländle, V., Gartner, C., Goerg, C., Kaul, N., Messer, S., Burkhardt, D., Sander, C., Orthen, R., Kaes, S., Baumer, A., Dodos, F., Barth, A., Schaeffer, G., Gaertner, J., Winkler, J., Fahrig, A., Aring, J., Wenzel, I., Steiner, S., Kliesch, A., Kratz, E., Winter, K., Schneider, P., Haag, A., Mutscher, I., Bosch, R., Taggeselle, J., Meixner, S., Schnabel, A., Shamalla, A., Hötz, H., Korinth, A., Rheinert, C., Mehltretter, G., Schön, B., Schön, N., Starflinger, A., Englmann, E., Baytok, G., Laschinger, T., Ritscher, G., Gerth, A., Dechering, D., Eckardt, L., Kuhlmann, M., Proskynitopoulos, N., Brunn, J., Foth, K., Axthelm, C., Hohensee, H., Eberhard, K., Turbanisch, S., Hassler, N., Koestler, A., Stenzel, G., Kschiwan, D., Schwefer, M., Neiner, S., Hettwer, S., Haeussler‐schuchardt, M., Degenhardt, R., Sennhenn, S., Brendel, M., Stoehr, A., Widjaja, W., Loehndorf, S., Logemann, A., Hoskamp, J., Grundt, J., Block, M., Ulrych, R., Reithmeier, A., Panagopoulos, V., Martignani, C., Bernucci, D., Fantecchi, E., Diemberger, I., Ziacchi, M., Biffi, M., Cimaglia, P., Frisoni, J., Giannini, I., Boni, S., Fumagalli, S., Pupo, S., Di Chiara, A., Mirone, P., Pesce, F., Zoccali, C., Malavasi, V.L., Mussagaliyeva, A., Ahyt, B., Salihova, Z., Koshum‐bayeva, K., Kerimkulova, A., Bairamukova, A., Lurina, B., Zuzans, R., Jegere, S., Mintale, I., Kupics, K., Jubele, K., Kalejs, O., Vanhear, K., Cachia, M., Abela, E., Warwicker, S., Tabone, T., Xuereb, R., Asanovic, D., Drakalovic, D., Vukmirovic, M., Pavlovic, N., Music, L., Bulatovic, N., Boskovic, A., Uiterwaal, H., Bijsterveld, N., Groot, J., Neefs, J., den Berg, N., Piersma, F., Wilde, A., Hagens, V., Es, J., Opstal, J., Rennes, B., Verheij, H., Breukers, W., Tjeerdsma, G., Nijmeijer, R., Wegink, D., Binnema, R., Said, S., Philippens, S., Doorn, W., Szili‐torok, T., Bhagwandien, R., Janse, P., Muskens, A., Eck, M., Gevers, R., Der Ven, N., Duygun, A., Rahel, B., Meeder, J., Vold, A., Holst Hansen, C., Engset, I., Dyduch‐fejklowicz, B., Koba, E., Cichocka, M., Sokal, A., Kubicius, A., Pruchniewicz, E., Kowalik‐sztylc, A., Czapla, W., Mróz, I., Kozlowski, M., Pawlowski, T., Tendera, M., Winiarska‐filipek, A., Fidyk, A., Slowikowski, A., Haberka, M., Lachor‐broda, M., Biedron, M., Gasior, Z., Kołodziej, M., Janion, M., Gorczyca‐michta, I., Wozakowska‐kaplon, B., Stasiak, M., Jakubowski, P., Ciurus, T., Drozdz, J., Simiera, M., Zajac, P., Wcislo, T., Zycinski, P., Kasprzak, J., Olejnik, A., Harc‐dyl, E., Miarka, J., Pasieka, M., Ziemińska‐łuć, M., Bujak, W., Śliwiński, A., Grech, A., Morka, J., Petrykowska, K., Prasał, M., Hordyński, G., Feusette, P., Lipski, P., Wester, A., Streb, W., Romanek, J., Woźniak, P., Chlebuś, M., Szafarz, P., Stanik, W., Zakrzewski, M., Kaźmierczak, J., Przybylska, A., Skorek, E., Błaszczyk, H., Stępień, M., Szabowski, S., Krysiak, W., Szymańska, M., Karasiński, J., Blicharz, J., Skura, M., Hałas, K., Michalczyk, L., Orski, Z., Krzyżanowski, K., Skrobowski, A., Zieliński, L., Tomaszewska‐kiecana, M., Dłużniewski, M., Kiliszek, M., Peller, M., Budnik, M., Balsam, P., Opolski, G., Tymińska, A., Ozierański, K., Wancerz, A., Borowiec, A., Majos, E., Dabrowski, R., Szwed, H., Musialik‐lydka, A., Leopold‐jadczyk, A., Jedrzejczyk‐patej, E., Koziel, M., Mazurek, M., Krzemien‐wolska, K., Starosta, P., Nowalany‐kozielska, E., Orzechowska, A., Szpot, M., Staszel, M., Almeida, S., Pereira, H., Brandão Alves, L., Miranda, R., Ribeiro, L., Costa, F., Morgado, F., Carmo, P., Galvao Santos, P., Bernardo, R., Adragão, P., Ferreira da Silva, G., Peres, M., Alves, M., Leal, M., Cordeiro, A., Magalhães, P., Fontes, P., Leão, S., Delgado, A., Costa, A., Marmelo, B., Rodrigues, B., Moreira, D., Santos, J., Santos, L., Terchet, A., Darabantiu, D., Mercea, S., Turcin Halka, V., Pop Moldovan, A., Gabor, A., Doka, B., Catanescu, G., Rus, H., Oboroceanu, L., Bobescu, E., Popescu, R., Dan, A., Buzea, A., Daha, I., Neuhoff, I., Baluta, M., Ploesteanu, R., Dumitrache, N., Vintila, M., Daraban, A., Japie, C., Badila, E., Tewelde, H., Hostiuc, M., Frunza, S., Tintea, E., Bartos, D., Ciobanu, A., Popescu, I., Toma, N., Gherghinescu, C., Cretu, D., Patrascu, N., Stoicescu, C., Udroiu, C., Bicescu, G., Vintila, V., Vinereanu, D., Cinteza, M., Rimbas, R., Grecu, M., Cozma, A., Boros, F., Ille, M., Tica, O., Tor, R., Corina, A., Jeewooth, A., Maria, B., Georgiana, C., Natalia, C., Alin, D., Dinu‐andrei, D., Livia, M., Daniela, R., Larisa, R., Umaar, S., Tamara, T., Ioachim Popescu, M., Nistor, D., Sus, I., Coborosanu, O., Alina‐ramona, N., Dan, R., Petrescu, L., Ionescu, G., Vacarescu, C., Goanta, E., Mangea, M., Ionac, A., Mornos, C., Cozma, D., Pescariu, S., Solodovnicova, E., Soldatova, I., Shutova, J., Tjuleneva, L., Zubova, T., Uskov, V., Obukhov, D., Rusanova, G., Isakova, N., Odinsova, S., Arhipova, T., Kazakevich, E., Zavyalova, O., Novikova, T., Riabaia, I., Zhigalov, S., Drozdova, E., Luchkina, I., Monogarova, Y., Hegya, D., Rodionova, L., Nevzorova, V., Lusanova, O., Arandjelovic, A., Toncev, D., Vukmirovic, L., Radisavljevic, M., Milanov, M., Sekularac, N., Zdravkovic, M., Hinic, S., Dimkovic, S., Acimovic, T., Saric, J., Radovanovic, S., Kocijancic, A., Obrenovic‐kircanski, B., Kalimanovska Ostric, D., Simic, D., Jovanovic, I., Petrovic, I., Polovina, M., Vukicevic, M., Tomasevic, M., Mujovic, N., Radivojevic, N., Petrovic, O., Aleksandric, S., Kovacevic, V., Mijatovic, Z., Ivanovic, B., Tesic, M., Ristic, A., Vujisic‐tesic, B., Nedeljkovic, M., Karadzic, A., Uscumlic, A., Prodanovic, M., Zlatar, M., Asanin, M., Bisenic, B., Vasic, V., Popovic, Z., Djikic, D., Sipic, M., Peric, V., Dejanovic, B., Milosevic, N., Backovic, S., Stevanovic, A., Andric, A., Pencic, B., Pavlovic‐kleut, M., Celic, V., Pavlovic, M., Petrovic, M., Vuleta, M., Petrovic, N., Simovic, S., Savovic, Z., Milanov, S., Davidovic, G., Iric‐cupic, V., Djordjevic, D., Damjanovic, M., Zdravkovic, S., Topic, V., Stanojevic, D., Randjelovic, M., Jankovic‐tomasevic, R., Atanaskovic, V., Antic, S., Simonovic, D., Stojanovic, M., Stojanovic, S., Mitic, V., Ilic, V., Petrovic, D., Deljanin Ilic, M., Ilic, S., Stoickov, V., Markovic, S., Mijatovic, A., Tanasic, D., Radakovic, G., Peranovic, J., Panic‐jelic, N., Vujadinovic, O., Pajic, P., Bekic, S., Kovacevic, S., García Fernandez, A., Perez Cabeza, A., Anguita, M., Tercedor Sanchez, L., Mau, E., Loayssa, J., Ayarra, M., Carpintero, M., Roldán Rabadan, I., Gil Ortega, M., Tello Montoliu, A., Orenes Piñero, E., Manzano Fernández, S., Romero Aniorte, A., Veliz Martínez, A., Quintana Giner, M., Ballesteros, G., Palacio, M., Alcalde, O., García‐bolao, I., Bertomeu Gonzalez, V., Otero‐raviña, F., García Seara, J., Gonzalez Juanatey, J., Dayal, N., Maziarski, P., Gentil‐baron, P., Koç, M., Onrat, E., Dural, I., Yilmaz, K., Özin, B., Tan Kurklu, S., Atmaca, Y., Canpolat, U., Tokgozoglu, L., Dolu, A., Demirtas, B., Sahin, D., Ozcan Celebi, O., Gagirci, G., Turk, U.O., Ari, H., Polat, N., Toprak, N., Sucu, M., Akin Serdar, O., Taha Alper, A., Kepez, A., Yuksel, Y., Uzunselvi, A., Yuksel, S., Sahin, M., Kayapinar, O., Ozcan, T., Kaya, H., Yilmaz, M., Kutlu, M., Demir, M., Gibbs, C., Kaminskiene, S., Bryce, M., Skinner, A., Belcher, G., Hunt, J., Stancombe, L., Holbrook, B., Peters, C., Tettersell, S., Shantsila, A., Senoo, K., Proietti, M., Russell, K., Domingos, P., Hussain, S., Partridge, J., Haynes, R., Bahadur, S., Brown, R., Mcmahon, S., Mcdonald, J., Balachandran, K., Singh, R., Garg, S., Desai, H., Davies, K., Goddard, W., Galasko, G., Rahman, I., Chua, Y., Payne, O., Preston, S., Brennan, O., Pedley, L., Whiteside, C., Dickinson, C., Brown, J., Jones, K., Benham, L., Brady, R., Buchanan, L., Ashton, A., Crowther, H., Fairlamb, H., Thornthwaite, S., Relph, C., Mcskeane, A., Poultney, U., Kelsall, N., Rice, P., Wilson, T., Wrigley, M., Kaba, R., Patel, T., Young, E., Law, J., Runnett, C., Thomas, H., Mckie, H., Fuller, J., Pick, S., Sharp, A., Hunt, A., Thorpe, K., Hardman, C., Cusack, E., Adams, L., Hough, M., Keenan, S., Bowring, A., Watts, J., Zaman, J., Goffin, K., Nutt, H., Beerachee, Y., Featherstone, J., Mills, C., Pearson, J., Stephenson, L., Grant, S., Wilson, A., Hawksworth, C., Alam, I., Robinson, M., Ryan, S., Egdell, R., Gibson, E., Holland, M., Leonard, D., Mishra, B., Ahmad, S., Randall, H., Hill, J., Reid, L., George, M., Mckinley, S., Brockway, L., Milligan, W., Sobolewska, J., Muir, J., Tuckis, L., Winstanley, L., Jacob, P., Kaye, S., Morby, L., Jan, A., Sewell, T., Boos, C., Wadams, B., Cope, C., Jefferey, P., Andrews, N., Getty, A., Suttling, A., Turner, C., Hudson, K., Austin, R., Howe, S., Iqbal, R., Gandhi, N., Brophy, K., Mirza, P., Willard, E., Collins, S., Ndlovu, N., Subkovas, E., Karthikeyan, V., Waggett, L., Wood, A., Bolger, A., Stockport, J., Evans, L., Harman, E., Starling, J., Williams, L., Saul, V., Sinha, M., Bell, L., Tudgay, S., Kemp, S., Frost, L., Ingram, T., Loughlin, A., Adams, C., Adams, M., Hurford, F., Owen, C., Miller, C., Donaldson, D., Tivenan, H., Button, H., Nasser, A., Jhagra, O., Stidolph, B., Brown, C., Livingstone, C., Duffy, M., Madgwick, P., Roberts, P., Greenwood, E., Fletcher, L., Beveridge, M., Earles, S., Mckenzie, D., Beacock, D., Dayer, M., Seddon, M., Greenwell, D., Luxton, F., Venn, F., Mills, H., Rewbury, J., James, K., Roberts, K., Tonks, L., Felmeden, D., Taggu, W., Summerhayes, A., Hughes, D., Sutton, J., Felmeden, L., Khan, M., Walker, E., Norris, L., O’donohoe, L., Mozid, A., Dymond, H., Lloyd‐jones, H., Saunders, G., Simmons, D., Coles, D., Cotterill, D., Beech, S., Kidd, S., Wrigley, B., Petkar, S., Smallwood, A., Jones, R., Radford, E., Milgate, S., Metherell, S., Cottam, V., Buckley, C., Broadley, A., Wood, D., Allison, J., Rennie, K., Balian, L., Howard, L., Pippard, L., Board, S., Pitt‐kerby, T., Garnier, Sophie, Hengstenberg, Christian, Lamblin, Nicolas, Dubourg, Olivier, de Groote, Pascal, Trochu, Jean-Noël, Arbustini, Eloisa, Esslinger, Ulrike, Barton, Paul, Meder, Benjamin, Katus, Hugo, Frese, Karen, Komajda, Michel, Cook, Stuart, Isnard, Richard, Tiret, Laurence, Villard, Eric, Charron, Philippe, Angoulvant, D., University of Belgrade [Belgrade], Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Océan du Large et Variabilité Climatique (OLVAC), Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Éducation Éthique Santé EA 7505 (EES), Université de Tours (UT), University of Liverpool, Aalborg University [Denmark] (AAU), Maria Cecilia Hospital [Cotignola], Valorex SAS, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Department of Internal Medicine II, Division of Respirology, University of Regensburg, Regensburg, Germany, Universität Regensburg (UR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré [AP-HP], Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), IRCCS - Pavia, Heidelberg University Hospital [Heidelberg], Université Pierre et Marie Curie - Paris 6 (UPMC), Robert Steiner MRI Unit, Imperial College London, Université de Montréal (UdeM), CHU Tenon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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Male ,medicine.medical_specialty ,Vitamin K ,MEDLINE ,Vitamin k ,Poor quality ,Decision Support Techniques ,[SHS]Humanities and Social Sciences ,Thromboembolism ,Physiology (medical) ,Internal medicine ,Atrial Fibrillation ,Humans ,Medicine ,In patient ,Blood Coagulation ,Stroke ,ComputingMilieux_MISCELLANEOUS ,Framingham Risk Score ,business.industry ,Anticoagulants ,Atrial fibrillation ,medicine.disease ,Surgery ,Cohort ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
This editorial refers to ‘Evaluation of SAMe-TT2R2 risk score for predicting the quality of anticoagulation control in a real-world cohort of patients with non-valvular atrial fibrillation on vitamin-K antagonists’ by M. R.R.-Y. Abumuaileq et al. , doi:10.1093/europace/euu353. Maintaining the therapeutic range in patients treated with vitamin K antagonists (VKAs) had always been challenging whilst the potential consequences of deviating from the optimal average time in therapeutic range(TTR) are deleterious in patients with atrial fibrillation (AF), given the risk for thromboembolic and bleeding events.1,2 Various clinical decision-making tools have been developed to help decision-making in the management of AF patients. In 2013, a new score—with the acronym SAMe-TT2R2—was proposed to help identify those patients who were likely to have a propensity to poor INR control (as reflected by average time in the therapeutic range [TTR] 2).3 This score was derived from a trial cohort and thus independent validation in ‘real-world’ AF cohorts would be needed. In the current issue of EP-Europace , Abumaileq et al. 4 performed a retrospective analysis of a cohort of outpatients with non-valvular AF and found that SAMe-TT2R2 could indeed represented a useful clinical tool to identify a poor quality of anticoagulation control with VKAs. The predictive ability of SAMe-TT2R2 was acceptable for identifying low TTR and improved when integrated with other clinical characteristics. A strong relationship …
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- 2015
25. N‐terminal pro brain natriuretic peptide eliminates the prognostic effect of atrial fibrillation in patients with chronic heart failure.
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Schnorbach, Johannes, Fröhlich, Hanna, Täger, Tobias, Corletto, Anna, Katus, Hugo A., and Frankenstein, Lutz
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BRAIN natriuretic factor ,ATRIAL fibrillation ,HEART failure - Abstract
Aims: Co‐morbid atrial fibrillation (AF) increases both mortality and N‐terminal pro brain natriuretic peptide (NT‐proBNP) concentrations in patients with chronic heart failure (CHF). It is unclear whether AF worsens prognosis independently from NT‐proBNP concentrations. If AF was an independent risk factor, NT‐proBNP levels for outcome prediction would need to be adjusted in patients with AF. We aimed to analyse the influence of AF on the prognostic value of NT‐proBNP in patients with CHF. Methods and results: A total of 2541 consecutive CHF patients with sinus rhythm (SR) or AF were identified in the outpatients' CHF registry of the University of Heidelberg, Germany. Of these, 250 patients with SR were individually matched to 250 patients with AF with respect to NT‐proBNP, New York Heart Association functional class, sex, age, and aetiology of CHF. In the general sample, both AF and NT‐proBNP were associated with all‐cause mortality [hazard ratio (HR) = 1.96, 95% confidence interval (CI) 1.61–2.39, P < 0.001; and HR = 1.03 per 1000 ng/L increase, 95% CI 1.02 to 1.04, P < 0.001, respectively]. After matching, NT‐proBNP retained its prognostic power (HR = 1.13 per 1000 ng/L increase, 95% CI 1.10 to 1.16, P < 0.001), but AF did not (HR = 0.91, 95% CI 0.66 to 1.25, P = 0.56). Despite similar prognosis, matched patients with SR were in more advanced CHF than were AF patients as indicated by a lower left ventricular ejection fraction (30 ± 13% vs. 34 ± 14%, P < 0.001). Conclusions: The prognostic value of NT‐proBNP in CHF is not influenced by concomitant AF. AF, in return, might be a surrogate of a worse cardiac condition rather than an independent risk factor. [ABSTRACT FROM AUTHOR]
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- 2019
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26. Identification of the A293 (AVE1231) Binding Site in the Cardiac Two-Pore-Domain Potassium Channel TASK-1: a Common Low Affinity Antiarrhythmic Drug Binding Site.
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Wiedmann, Felix, Kiper, Aytug K., Bedoya, Mauricio, Ratte, Antonius, Rinné, Susanne, Kraft, Manuel, Waibel, Maximilian, Anad, Priya, Wenzel, Wolfgang, González, Wendy, Katus, Hugo A., Decher, Niels, and Schmidt, Constanze
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POTASSIUM channels ,GENE expression ,MICRORNA ,ATRIAL fibrillation ,CANCER cells - Abstract
Background/Aims: The two-pore-domain potassium channel TASK-1 regulates atrial action potential duration. Due to the atrium-specific expression of TASK-1 in the human heart and the functional upregulation of TASK-1 currents in atrial fibrillation (AF), TASK-1 represents a promising target for the treatment of AF. Therefore, detailed knowledge of the molecular determinants of TASK-1 inhibition may help to identify new drugs for the future therapy of AF. In the current study, the molecular determinants of TASK-1 inhibition by the potent and antiarrhythmic compound A293 (AVE1231) were studied in detail. Methods: Alanine-scanning mutagenesis together with two-electrode voltage-clamp recordings were combined with in silico docking experiments. Results: Here, we have identified Q126 located in the M2 segment together with L239 and N240 of the M4 segment as amino acids essential for the A293-mediated inhibition of TASK‑1. These data indicate a binding site which is different to that of A1899 for which also residues of the pore signature sequence and the late M4 segments are essential. Using in silico docking experiments, we propose a binding site at the lower end of the cytosolic pore, located at the entry to lateral side fenestrations of TASK-1. Strikingly, TASK-1 inhibition by the low affinity antiarrhythmic TASK‑1 blockers propafenone, amiodarone and carvedilol was also strongly diminished by mutations at this novel binding site. Conclusion: We have identified the A293 binding site in the central cavity of TASK-1 and propose that this site might represent a conserved site of action for many low affinity antiarrhythmic TASK-1 blockers. [ABSTRACT FROM AUTHOR]
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- 2019
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27. High-sensitivity cardiac troponin T as an independent predictor of stroke in patients admitted to an emergency department with atrial fibrillation.
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Vafaie, Mehrshad, Giannitsis, Evangelos, Mueller-Hennessen, Matthias, Biener, Moritz, Makarenko, Elena, Yueksel, Buelent, Katus, Hugo A., and Stoyanov, Kiril M.
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TROPONIN ,STROKE patients ,EMERGENCY medical services ,ATRIAL fibrillation ,PROTEINS ,CARDIOLOGY - Abstract
Aims: Elevated levels of high-sensitivity cardiac troponin T (hsTnT) are associated with adverse outcomes in numerous patient populations. Their value in prediction of stroke risk in patients with atrial fibrillation (AF) is in debate. Methods: The study population included 2898 consecutive patients presenting with AF to the emergency department of the Department of Cardiology, Heidelberg University Hospital. Associations between hsTnT and stroke risk were assessed using multivariable Cox regression. Results: Elevated hsTnT levels (>14 ng/L) were associated with increased risk of stroke. Even after adjustment for various risk factors, elevated hsTnT remained independently associated with stroke risk in patients with AF, adjusted hazard ratio 2.35 [95% confidence interval (CI): 1.26–4.36] (P = 0.007). These results were consistent across important subgroups (age, renal function, ejection fraction, CHA
2 DS2 -VASc score and main admission diagnosis). For hsTnT, area under the receiver-operating-characteristic curve (AUC) was 0.659 [95% CI: 0.575–0.742], compared to 0.610 [95% CI: 0.526–0.694] for the CHA2 DS2 -VASc score. Inclusion of hsTnT in the multivariable model for stroke risk prediction consisting of all variables of the CHA2 DS2 -VASc score was associated with a significant improvement of its discriminatory power. Conclusion: Elevated hsTnT levels are significantly associated with higher risk of stroke and provide prognostic information independent of CHA2 DS2 -VASc score variables. Measurement of hsTnT may improve prediction of stroke risk in patients presenting to an emergency department with AF as compared to risk stratification based only on clinical variables. [ABSTRACT FROM AUTHOR]- Published
- 2019
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28. Cochrane corner: NOACs in atrial fibrillation patients post-percutaneous coronary intervention.
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Al Said, Samer, Katus, Hugo A., and Alabed, Samer
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ATRIAL fibrillation ,PLATELET aggregation inhibitors ,ANTICOAGULANTS ,ACUTE coronary syndrome ,DUAL diagnosis ,RANDOMIZED controlled trials - Published
- 2020
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29. Inhibition of Histone Deacetylases Induces K+ Channel Remodeling and Action Potential Prolongation in HL-1 Atrial Cardiomyocytes.
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Lugenbiel, Patrick, Govorov, Katharina, Rahm, Ann-Kathrin, Wieder, Teresa, Gramlich, Dominik, Syren, Pascal, Weiberg, Nadine, Seyler, Claudia, Katus, Hugo A., and Thomas, Dierk
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ELECTROPHYSIOLOGY ,HISTONE deacetylase ,GENE expression ,ATRIAL fibrillation ,ION channels - Abstract
Background/Aims: Cardiac arrhythmias are triggered by environmental stimuli that may modulate expression of cardiac ion channels. Underlying epigenetic regulation of cardiac electrophysiology remains incompletely understood. Histone deacetylases (HDACs) control gene expression and cardiac integrity. We hypothesized that class I/II HDACs transcriptionally regulate ion channel expression and determine action potential duration (APD) in cardiac myocytes.Methods: Global class I/II HDAC inhibition was achieved by administration of trichostatin A (TSA). HDAC-mediated effects on K+ channel expression and electrophysiological function were evaluated in murine atrial cardiomyocytes (HL-1 cells) using real-time PCR, Western blot, and patch clamp analyses. Electrical tachypacing was employed to recapitulate arrhythmia-related effects on ion channel remodeling in the absence and presence of HDAC inhibition.Results: Global HDAC inhibition increased histone acetylation and prolonged APD90 in atrial cardiomyocytes compared to untreated control cells. Transcript levels of voltage-gated or inwardly rectifying K+ channels Kcnq1, Kcnj3 and Kcnj5 were significantly reduced, whereas Kcnk2, Kcnj2 and Kcnd3 mRNAs were upregulated. Ion channel remodeling was similarly observed at protein level. Short-term tachypacing did not induce significant transcriptional K+ channel remodeling.Conclusion: The present findings link class I/II HDAC activity to regulation of ion channel expression and action potential duration in atrial cardiomyocytes. Clinical implications for HDAC-based antiarrhythmic therapy and cardiac safety of HDAC inhibitors require further investigation. [ABSTRACT FROM AUTHOR]- Published
- 2018
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30. Prognostic value of elevated high-sensitivity cardiac troponin T in patients admitted to an emergency department with atrial fibrillation.
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Stoyanov, Kiril M., Giannitsis, Evangelos, Biener, Moritz, Mueller-Hennessen, Matthias, Arens, Katharina, Katus, Hugo A., and Vafaie, Mehrshad
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Aims: Elevated levels of high-sensitivity cardiac troponin T (hsTnT) indicate underlying heart disease and are known to predict adverse outcomes in various patient populations. Their role in atrial fibrillation (AF) is still under debate.Methods and results: This retrospective study included 2898 consecutive patients presenting with AF to the emergency department of the Department of Cardiology, Heidelberg University Hospital. Multivariable Cox regression was used to assess associations between hsTnT and mortality. Elevated hsTnT levels were associated with increased risk of all-cause mortality in all patients with AF, as well as in each subtype of AF. After adjustment for multiple risk factors, both detectable hsTnT below the 99th percentile (5-14 ng/L, adjusted hazard ratio (HR): 4.86 [95% CI: 1.77-13.34], P = 0.002) and elevated hsTnT (>14 ng/L, adjusted HR: 13.42 [95% CI: 4.95-36.40], P < 0.001) were associated with a higher risk of mortality in patients with AF, compared to undetectable hsTnT (<5 ng/L). Elevated hsTnT was also associated with higher mortality after exclusion of patients with myocardial infarction, as well as in the subgroup of patients with AF as main admission diagnosis. The inclusion of hsTnT significantly improved the performance of the multivariable model for mortality prediction.Conclusion: Elevated hsTnT levels are associated with higher mortality in patients with AF, and provide added prognostic information independent of major cardiovascular risk factors and clinical characteristics. Measurement of hsTnT should be considered for risk assessment in patients presenting to an emergency department with AF.Clinical trial registration: http://www.clinicaltrials.gov; Unique identifier: NCT02542189. [ABSTRACT FROM AUTHOR]- Published
- 2018
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31. Influence of irregular heart rhythm on radiation exposure, image quality and diagnostic impact of cardiac computed tomography angiography in 4,339 patients. Data from the German Cardiac Computed Tomography Registry.
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Korosoglou, Grigorios, Marwan, Mohamed, Giusca, Sorin, Schmermund, Axel, Schneider, Steffen, Bruder, Oliver, Hausleiter, Jörg, Schroeder, Stephen, Leber, Alexander, Limbourg, Tobias, Gitsioudis, Gitsios, Rixe, Johannes, Zahn, Ralf, Katus, Hugo A., Achenbach, Stephan, and Senges, Jochen
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Background Coronary computed tomography angiography (coronary CTA) provides non-invasive evaluation of the coronary arteries with high precision for the detection of significant coronary artery disease (CAD). Aim To investigate whether irregular heart rhythm including atrial fibrillation and premature beats during data acquisition influences (i) radiation and contrast media exposure, (ii) number of non-evaluable coronary segments and (iii) diagnostic impact of coronary CTA. Methods Twelve tertiary care centers with ≥64 slice CT scanners and ≥5 years of experience with cardiovascular imaging participated in this registry. Between 2009 and 2014, 4339 examinations were analysed in patients who underwent clinically indicated coronary CTA for suspected CAD. Clinical and epidemiologic data were gathered from all patients. In addition, clinical presentation, heart rate and rhythm during the scan, Agatston score, radiation and contrast media exposure and the diagnostic impact of coronary CTA were systematically analysed. Results Of 4339 patients in total, 260 (6.0%) had irregular heart rhythm, whereas the remaining 4079 (94.0%) had stable sinus rhythm. Patients with irregular heart rhythm were older (63.2 ± 12.5yrs versus 58.6 ± 11.4yrs. p < 0.001), exhibited a higher rate of pathologic stress tests before CTA (37.1% versus 26.1%, p < 0.01) and higher heart rates during CTA compared to those with sinus rhythm (62.5 ± 11.6bpm versus 58.9 ± 8.5bpm, p < 0.001). Both contrast media exposure and radiation exposure were significantly higher in patients with irregular heart rhythm (90 mL (95%CI = 80–110 mL) versus 80 mL (95%CI = 70–90 mL) and 6.2 mSv (95%CI = 2.5–11.7) versus 3.3 mSv (95%CI = 1.7–6.9), p < 0.001 for both). Coronary CTA excluded significant CAD less frequently in patients with irregular heart rhythm (32.9% versus 44.8%, p < 0.001). This was attributed to the higher rate of examinations with at least one non-diagnostic coronary segment in patients with irregular heart rhythm (10.8% versus 4.6%, p < 0.001). Subsequent invasive angiography could be avoided in 47.2% of patients with irregular heart rhythm compared to 52.9% of patients with sinus rhythm (p = NS), whereas downstream stress testing was recommended in 3.2% of patients with irregular heart rhythm versus 4.0% of patients with sinus rhythm (p = NS). Conclusion A significant number of patients scheduled for coronary CTA have irregular heart rhythm in a real-world clinical setting. In such patients, heart rate during coronary CTA is higher, possibly resulting in (i) higher radiation and contrast agent exposure and (ii) more frequent coronary CTA examinations with at least one non-diagnostic coronary artery segment. However, this does not seem to lead to increased downstream stress testing or subsequent invasive procedures. [ABSTRACT FROM AUTHOR]
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- 2018
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32. Chronic digitalis therapy in patients before heart transplantation is an independent risk factor for increased posttransplant mortality.
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Rivinius, Rasmus, Helmschrott, Matthias, Ruhparwar, Arjang, Rahm, Ann-Kathrin, Darche, Fabrice F., Thomas, Dierk, Bruckner, Tom, Ehlermann, Philipp, Katus, Hugo A., and Doesch, Andreas O.
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HEART failure treatment ,CHRONIC diseases ,DIGITALIS (Drug) ,HEART transplantation ,MORTALITY risk factors - Abstract
Objectives: Digitalis therapy (digoxin or digitoxin) in patients with heart failure is subject to an ongoing debate. Recent data suggest an increased mortality in patients receiving digitalis. This study investigated the effects of chronic digitalis therapy prior to heart transplantation (HTX) on posttransplant outcomes.Patients and Methods: This was a retrospective, observational, single-center study. It comprised 530 adult patients who were heart-transplanted at Heidelberg University Hospital between 1989 and 2012. Patients with digitalis prior to HTX (≥3 months) were compared to those without (no or <3 months of digitalis). Patients with digitalis were further subdivided into patients receiving digoxin or digitoxin. Primary outcomes were early posttransplant atrial fibrillation and mortality.Results: A total of 347 patients (65.5%) had digitalis before HTX. Of these, 180 received digoxin (51.9%) and 167 received digitoxin (48.1%). Patients with digitalis before HTX had a significantly lower 30-day (P=0.0148) and 2-year (P=0.0473) survival. There was no significant difference between digoxin and digitoxin in 30-day (P=0.9466) or 2-year (P=0.0723) survival. Multivariate analysis for posttransplant 30-day mortality showed pretransplant digitalis therapy as an independent risk factor (hazard ratio =2.097, CI: 1.036-4.248, P=0.0397). Regarding atrial fibrillation in the early posttransplant period, there was neither a statistically significant difference between patients with and without digitalis (P=0.1327) nor between patients with digoxin or digitoxin (P=0.5867).Conclusion: Digitalis in patients before HTX is an independent risk factor for increased posttransplant mortality. [ABSTRACT FROM AUTHOR]- Published
- 2017
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33. The influence of surgical technique on early posttransplant atrial fibrillation - comparison of biatrial, bicaval, and total orthotopic heart transplantation.
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Rivinius, Rasmus, Helmschrott, Matthias, Ruhparwar, Arjang, Erbel, Christian, Gleissner, Christian A., Darche, Fabrice F., Thomas, Dierk, Bruckner, Tom, Katus, Hugo A., and Doesch, Andreas O.
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CARDIAC patients ,ATRIAL fibrillation ,HEART transplantation ,OPERATIVE surgery ,MORTALITY - Abstract
Purpose: Early posttransplant atrial fibrillation (AF) has been associated with worse clinical outcomes after heart transplantation (HTX). The type of surgical technique may constitute a relevant risk factor for AF.Patients and Methods: This retrospective single-center study included 530 adult patients. Patients were stratified by surgical technique (biatrial, bicaval, or total orthotopic HTX) and early posttransplant heart rhythm (AF or sinus rhythm). Univariate and multivariate analyses were performed to evaluate risk factors for AF.Results: A total of 161 patients received biatrial HTX (30.4%), 115 bicaval HTX (21.7%), and 254 total orthotopic HTX (47.9%). Sixty-one of 530 patients developed early posttransplant AF (11.5%). Patients with AF showed a statistically inferior 5-year survival compared to those with sinus rhythm (P<0.0001). Total orthotopic HTX had the lowest rate of AF (total orthotopic HTX [6.3%], bicaval HTX [14.8%], biatrial HTX [17.4%], P=0.0012). Multivariate analysis showed pretransplant valvular heart disease (P=0.0372), posttransplant enlarged left atrium (P=0.0066), posttransplant mitral regurgitation (P=0.0370), and non-total orthotopic HTX (P=0.0112) as risk factors for AF.Conclusion: Early posttransplant AF was associated with increased mortality (P<0.0001). Total orthotopic HTX showed the lowest rate of AF compared to biatrial or bicaval HTX (P=0.0012). [ABSTRACT FROM AUTHOR]- Published
- 2017
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34. TREK-1 (K2P2.1) K+ channels are suppressed in patients with atrial fibrillation and heart failure and provide therapeutic targets for rhythm control.
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Lugenbiel, Patrick, Wenz, Fabian, Syren, Pascal, Geschwill, Pascal, Govorov, Katharina, Seyler, Claudia, Frank, Derk, Schweizer, Patrick A., Franke, Jennifer, Weis, Tanja, Bruehl, Claus, Schmack, Bastian, Ruhparwar, Arjang, Karck, Matthias, Frey, Norbert, Katus, Hugo A., and Thomas, Dierk
- Abstract
Atrial fibrillation (AF) is the most common cardiac arrhythmia. Concomitant heart failure (HF) poses a particular therapeutic challenge and is associated with prolonged atrial electrical refractoriness compared with non-failing hearts. We hypothesized that downregulation of atrial repolarizing TREK-1 (K
2P 2.1) K+ channels contributes to electrical remodeling during AF with HF, and that TREK-1 gene transfer would provide rhythm control via normalization of atrial effective refractory periods in this AF subset. In patients with chronic AF and HF, atrial TREK-1 mRNA levels were reduced by 82% (left atrium) and 81% (right atrium) compared with sinus rhythm (SR) subjects. Human findings were recapitulated in a porcine model of atrial tachypacing-induced AF and reduced left ventricular function. TREK-1 mRNA (−66%) and protein (−61%) was suppressed in AF animals at 14-day follow-up compared with SR controls. Downregulation of repolarizing TREK-1 channels was associated with prolongation of atrial effective refractory periods versus baseline conditions, consistent with prior observations in humans with HF. In a preclinical therapeutic approach, pigs were randomized to either atrial Ad-TREK-1 gene therapy or sham treatment. Gene transfer effectively increased TREK-1 protein levels and attenuated atrial effective refractory period prolongation in the porcine AF model. Ad-TREK-1 increased the SR prevalence to 62% during follow-up in AF animals, compared to 35% in the untreated AF group. In conclusion, TREK-1 downregulation and rhythm control by Ad-TREK-1 transfer suggest mechanistic and potential therapeutic significance of TREK-1 channels in a subgroup of AF patients with HF and prolonged atrial effective refractory periods. Functional correction of ionic remodeling through TREK-1 gene therapy represents a novel paradigm to optimize and specify AF management. [ABSTRACT FROM AUTHOR]- Published
- 2017
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35. A Simple, Non-Invasive Score to Predict Paroxysmal Atrial Fibrillation.
- Author
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Kallenberger, Stefan M., Schmid, Christian, Wiedmann, Felix, Mereles, Derliz, Katus, Hugo A., Thomas, Dierk, and Schmidt, Constanze
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ATRIAL fibrillation diagnosis ,ATRIAL fibrillation ,STROKE risk factors ,ECHOCARDIOGRAPHY ,MEDICAL needs assessment ,MEDICAL practice ,PROGNOSIS - Abstract
Paroxysmal atrial fibrillation (pAF) is a major risk factor for stroke but remains often unobserved. To predict the presence of pAF, we developed model scores based on echocardiographic and other clinical parameters from routine cardiac assessment. The scores can be easily implemented to clinical practice and might improve the early detection of pAF. In total, 47 echocardiographic and other clinical parameters were collected from 1000 patients with sinus rhythm (SR; n = 728), pAF (n = 161) and cAF (n = 111). We developed logistic models for classifying between pAF and SR that were reduced to the most predictive parameters. To facilitate clinical implementation, linear scores were derived. To study the pathophysiological progression to cAF, we analogously developed models for cAF prediction. For classification between pAF and SR, amongst 12 selected model parameters, the most predictive variables were tissue Doppler imaging velocity during atrial contraction (TDI, A’), left atrial diameter, age and aortic root diameter. Models for classifying between pAF and SR or between cAF and SR showed areas under the ROC curves of 0.80 or 0.93, which resembles classifiers with high discriminative power. The novel risk scores were suitable to predict the presence of pAF based on variables readily available from routine cardiac assessment. Modelling helped to quantitatively characterize the pathophysiologic transition from SR via pAF to cAF. Applying the scores may improve the early detection of pAF and might be used as decision aid for initiating preventive interventions to reduce AF-associated complications. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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36. Sex-related outcome of atrial fibrillation ablation: Insights from the German Ablation Registry.
- Author
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Zylla, Maura M., Brachmann, Johannes, Lewalter, Thorsten, Hoffmann, Ellen, Kuck, Karl-Heinz, Andresen, Dietrich, Willems, Stephan, Eckardt, Lars, Tebbenjohanns, Jürgen, Spitzer, Stefan G., Schumacher, Burghard, Hochadel, Matthias, Senges, Jochen, Katus, Hugo A., and Thomas, Dierk
- Abstract
Background: Stratification of patients with atrial fibrillation (AF) according to mechanistic and prognostic criteria may optimize the effectiveness and safety of catheter ablation. In women, AF is associated with more severe symptoms and worse prognosis.Objective: We sought to assess sex-related differences in catheter ablation procedures and outcome in a large cohort of patients with AF.Methods: A total of 3652 patients (1198 women [33%]; 2454 men [67%]) included in the German Ablation Registry were analyzed. Periprocedural parameters and outcome at 12-month follow-up were compared between male and female patients.Results: Women were older at the time of ablation (women: 63.6 years; men: 59.1 years; P < .0001) and exhibited a higher prevalence of paroxysmal AF (women: 72%; men: 61%; P < .0001). They were less often affected by cardiovascular disease and reduced left ventricular function. Energy application duration and overall procedure duration were shorter in women. Conversely, the rate of major inhospital complications was increased in female patients (1.9% vs 0.8%; P = .023) and mainly driven by major bleeding events. At follow-up, women experienced higher AF recurrence rates (women: 50%; men: 45%; P = .017) and more often received oral medication for rhythm and rate control. In addition, the rate of pacemaker implantation was higher in the female cohort. Women more frequently reported femoral access site complications (women: 6%; men: 3%; P < .001). Overall, male patients were more often free from AF-related symptoms and satisfied with the treatment.Conclusion: Catheter ablation of AF was associated with a distinct sex-related outcome and complication profile that requires consideration in clinical practice. [ABSTRACT FROM AUTHOR]- Published
- 2016
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37. Therapeutic targeting of two-pore-domain potassium (K2P) channels in the cardiovascular system.
- Author
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Wiedmann, Felix, Schmidt, Constanze, Lugenbiel, Patrick, Staudacher, Ingo, Rahm, Ann-Kathrin, Seyler, Claudia, Schweizer, Patrick A., Katus, Hugo A., and Thomas, Dierk
- Subjects
MYOCARDIAL depressants ,ARRHYTHMIA treatment ,ATRIAL fibrillation ,ION channels ,HEALTH outcome assessment - Abstract
The improvement of treatment strategies in cardiovascular medicine is an ongoing process that requires constant optimization. The ability of a therapeutic intervention to prevent cardiovascular pathology largely depends on its capacity to suppress the underlying mechanisms. Attenuation or reversal of disease-specific pathways has emerged as a promising paradigm, providing a mechanistic rationale for patient-tailored therapy. Two-pore-domain K
+ (K2P ) channels conduct outward K+ currents that stabilize the resting membrane potential and facilitate action potential repolarization. K2P expression in the cardiovascular system and polymodal K2P current regulation suggest functional significance and potential therapeutic roles of the channels. Recent work has focused primarily on K2P 1.1 [tandem of pore domains in a weak inwardly rectifying K+ channel (TWIK)-1], K2P 2.1 [TWIK-related K+ channel (TREK)-1], and K2P 3.1 [TWIK-related acid-sensitive K+ channel (TASK)-1] channels and their role in heart and vessels. K2P currents have been implicated in atrial and ventricular arrhythmogenesis and in setting the vascular tone. Furthermore, the association of genetic alterations in K2P 3.1 channels with atrial fibrillation, cardiac conduction disorders and pulmonary arterial hypertension demonstrates the relevance of the channels in cardiovascular disease. The function, regulation and clinical significance of cardiovascular K2P channels are summarized in the present review, and therapeutic options are emphasized. [ABSTRACT FROM AUTHOR]- Published
- 2016
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38. Catheter ablation of atrial fibrillation in patients with concomitant sinus bradycardia-Insights from the German Ablation Registry.
- Author
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Zylla, Maura M., Brachmann, Johannes, Lewalter, Thorsten, Hoffmann, Ellen, Kuck, Karl-Heinz, Andresen, Dietrich, Willems, Stephan, Hochadel, Matthias, Senges, Jochen, Katus, Hugo A., and Thomas, Dierk
- Abstract
Aims: This investigation addresses procedural characteristics of catheter ablation in patients with atrial fibrillation (AF) and sinus bradycardia.Methods: From the prospective, multi-center German Ablation Registry 1073 patients with sinus rhythm at the time of AF ablation were divided into two groups according to heart rate at start of procedure (A, <60 beats per minute (bpm), n=197; B, 60-99bpm, n=876).Results: Acute procedural success was high (≥98%) and similar between groups. Procedure duration and energy application time were increased in group A (180min vs. 155min and 2561s vs. 1879s, respectively). Major complications were more frequent in group A (2.2% vs. 0.5%), and a greater proportion of these patients was discharged under antiarrhythmic medication (64% vs. 52%).Conclusion: Catheter ablation of AF with concomitant sinus bradycardia is associated with high procedural efficacy, longer procedure- and energy application durations, and a slightly elevated complication rate. [ABSTRACT FROM AUTHOR]- Published
- 2016
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39. Catheter Ablation of Atrial Fibrillation in Patients With Heart Failure and Preserved Ejection Fraction.
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Zylla, Maura M., Leiner, Johannes, Rahm, Ann-Kathrin, Hoffmann, Tobias, Lugenbiel, Patrick, Schweizer, Patrick, Scholz, Eberhard, Mereles, Derliz, Kronsteiner, Dorothea, Kieser, Meinhard, Katus, Hugo A., Frey, Norbert, and Thomas, Dierk
- Abstract
Background: Coexistence of atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) is common, affecting morbidity and prognosis. This study evaluates outcome after cryoballoon ablation for AF in HFpEF compared with patients without heart failure. Methods: A total of 102 AF patients with left ventricular ejection fraction ≥50% undergoing cryoballoon ablation were prospectively enrolled. Baseline evaluation included echocardiography, stress echocardiography, 6-minute walk test, biomarkers, and quality of life assessment (Short-Form-36). Procedural parameters and clinical, functional and echocardiographic end points at follow-up ≥12 months after AF ablation were compared between patients with and without HFpEF. Results: Patients with HFpEF (n=24) were older (median, 74 years versus 65 years; P =0.001) more often female (83% versus 28%; P <0.001) and characterized by more pronounced AF-related symptoms (median European Heart Rhythm Association score 3 versus 2; P <0.001), higher left atrial pressures (median, 14 mm Hg versus 10 mm Hg; P =0.008), reduced left atrial-appendage velocity (median, 36 cm/s versus 59 cm/s; P <0.001), and reduced distance in the 6-minute walk test (median, 488 m versus 539 m; P <0.001). Patients with HFpEF more often experienced AF recurrence (57% versus 23%; P =0.003), repeat AF ablation (39% versus 14%; P =0.01) and AF-related rehospitalization (26% versus 7%; P =0.016). Heart failure symptoms and elevated cardiac biomarkers persisted, even in patients with HFpEF with successful rhythm control at follow-up. Echocardiographic follow-up showed progression of adverse left atrial remodeling and no relevant improvement in diastolic function in HFpEF. Quality of life improved in patients without HFpEF, whereas patients with HFpEF still exhibited a lower physical component summary score (median, 41.5 versus 53.4; P <0.004). Conclusions: Patients with HFpEF constitute a distinct subgroup with elevated risk for AF recurrence after cryoballon ablation. Functional hallmarks of HFpEF persist, irrespective of rhythm status at follow-up. Future research is needed to optimize treatment strategies in patients with HFpEF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04317911. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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40. Atrial Fibrillation Complicated by Heart Failure Induces Distinct Remodeling of Calcium Cycling Proteins.
- Author
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Lugenbiel, Patrick, Wenz, Fabian, Govorov, Katharina, Schweizer, Patrick A., Katus, Hugo A., and Thomas, Dierk
- Subjects
ATRIAL fibrillation ,HEART failure ,DISEASE complications ,CALCIUM in the body ,MORTALITY ,HOMEOSTASIS ,ECHOCARDIOGRAPHY - Abstract
Atrial fibrillation (AF) and heart failure (HF) are two of the most common cardiovascular diseases. They often coexist and account for significant morbidity and mortality. Alterations in cellular Ca
2+ homeostasis play a critical role in AF initiation and maintenance. This study was designed to specifically elucidate AF-associated remodeling of atrial Ca2+ cycling in the presence of mild HF. AF was induced in domestic pigs by atrial burst pacing. The animals underwent electrophysiologic and echocardiographic examinations. Ca2+ handling proteins were analyzed in right atrial tissue obtained from pigs with AF (day 7; n = 5) and compared to sinus rhythm (SR) controls (n = 5). During AF, animals exhibited reduction of left ventricular ejection fraction (from 73% to 58%) and prolonged atrial refractory periods. AF and HF were associated with suppression of protein kinase A (PKA)RII (-62%) and Ca2+ -calmodulin-dependent kinase II (CaMKII) δ by 37%, without changes in CaMKIIδ autophosphorylation. We further detected downregulation of L-type calcium channel (LTCC) subunit α2 (-75%), sarcoplasmic reticulum Ca2+ -ATPase (Serca) 2a (-29%), phosphorylated phospholamban (Ser16, -92%; Thr17, -70%), and phospho-ryanodine receptor 2 (RyR2) (Ser2808, -62%). Na+ -Ca2+ exchanger (NCX) levels were upregulated (+473%), whereas expression of Ser2814-phosphorylated RyR2 and LTCCα1c subunits was not significantly altered. In conclusion, AF produced distinct arrhythmogenic remodeling of Ca2+ handling in the presence of tachycardia-induced mild HF that is different from AF without structural alterations. The changes may provide a starting point for personalized approaches to AF treatment. [ABSTRACT FROM AUTHOR]- Published
- 2015
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41. Cloning, functional characterization, and remodeling of K2P3.1 (TASK-1) potassium channels in a porcine model of atrial fibrillation and heart failure.
- Author
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Schmidt, Constanze, Wiedmann, Felix, Langer, Clara, Tristram, Frank, Anand, Priya, Wenzel, Wolfgang, Lugenbiel, Patrick, Schweizer, Patrick A., Katus, Hugo A., and Thomas, Dierk
- Abstract
Background Effective treatment of atrial fibrillation (AF) remains an unmet need. Human K 2P 3.1 (TASK-1) K + channels display atrial-specific expression and may serve as novel antiarrhythmic targets. In rodents, inhibition of K 2P 3.1 causes prolongation of action potentials and QT intervals. We used a porcine model to further elucidate the significance of K 2P 3.1 in large mammals. Objective The purpose of this study was to study porcine (p)K 2P 3.1 channel function and cardiac expression and to analyze pK 2P 3.1 remodeling in AF and heart failure (HF). Methods The porcine K 2P 3.1 ortholog was amplified and characterized using voltage-clamp electrophysiology. K 2P 3.1 mRNA expression and remodeling were studied in domestic pigs during AF and HF induced by atrial burst pacing. Results Porcine K 2P 3.1 cDNA encodes a channel protein with 97% identity to human K 2P 3.1. K + currents recorded from Xenopus oocytes expressing pK 2P 3.1 were functionally and pharmacologically similar to their human counterparts. In the pig, K 2P 3.1 mRNA was predominantly expressed in atrial tissue. AF and HF were associated with reduction of K 2P 3.1 mRNA levels by 85.1% (right atrium) and 77.0% (left atrium) at 21-day follow-up. In contrast, ventricular K 2P 3.1 expression was low and not significantly affected by AF/HF. Conclusion Porcine K 2P 3.1 channels exhibit atrial expression and functional properties similar to their human orthologs, supporting a general role as antiarrhythmic drug targets. K 2P 3.1 down-regulation in AF with HF may indicate functional relevance of the channel that remains to be validated in prospective interventional studies. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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42. Discriminating atrial flutter from atrial fibrillation using a multilevel model of atrioventricular conduction.
- Author
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Scholz, Eberhard P., Kehrle, Florian, Vossel, Stephan, Hess, Alexander, Zitron, Edgar, Katus, Hugo A., and Sager, Sebastian
- Abstract
Background: The discrimination between atrial flutter (AFlu) and atrial fibrillation (AFib) can be made difficult by an irregular ventricular response owing to complex conduction phenomena within the atrioventricular (AV) node, known as multilevel AV block. We tested the hypothesis that a mathematical algorithm might be suitable to discriminate both arrhythmias. Objectives: To discriminate AFlu with irregular ventricular response from AFib based on the sequence of R-R intervals. Methods: Intracardiac recordings of 100 patients (50 patients with AFib and 50 patients with AFlu) were analyzed. On the basis of a numerical simulation of variable flutter frequencies followed by 2 levels of AV block in series, a given sequence of R-R intervals was analyzed. Results: Although the ventricular response displays absolute irregularity in AFib, the sequences of R-R intervals follow certain rules in AFlu. We find that using a mathematical simulation of multilevel AV block, based on the R-R sequence of 16 ventricular beats, a stability of atrial activation could be predicted with a sensitivity of 84% and a specificity of 74%. When limiting the ventricular rate to 125 beats/min, discrimination could be performed with a sensitivity of even 89% and a specificity of 80%. In cases of AFlu, the atrial cycle length could be predicted with high accuracy. Conclusion: On the basis of the electrophysiological mechanism of multilevel AV block, we developed a computer algorithm to discriminate between AFlu and Afib. This algorithm is able to predict the stability and cycle length of atrial activation for short R-R sequences with high accuracy. [Copyright &y& Elsevier]
- Published
- 2014
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43. Rotor Termination Is Critically Dependent on Kinetic Properties of IKur Inhibitors in an In Silico Model of Chronic Atrial Fibrillation.
- Author
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Scholz, Eberhard P., Carrillo-Bustamante, Paola, Fischer, Fathima, Wilhelms, Mathias, Zitron, Edgar, Dössel, Olaf, Katus, Hugo A., and Seemann, Gunnar
- Subjects
ATRIAL fibrillation ,INHIBITION of potassium channels ,PHARMACOKINETICS ,MYOCARDIAL depressants ,ELECTROPHYSIOLOGY ,BIOLOGICAL extinction ,TISSUE analysis - Abstract
Inhibition of the atrial ultra-rapid delayed rectifier potassium current (I
Kur ) represents a promising therapeutic strategy in the therapy of atrial fibrillation. However, experimental and clinical data on the antiarrhythmic efficacy remain controversial. We tested the hypothesis that antiarrhythmic effects of IKur inhibitors are dependent on kinetic properties of channel blockade. A mathematical description of IKur blockade was introduced into Courtemanche-Ramirez-Nattel models of normal and remodeled atrial electrophysiology. Effects of five model compounds with different kinetic properties were analyzed. Although a reduction of dominant frequencies could be observed in two dimensional tissue simulations for all compounds, a reduction of spiral wave activity could be only be detected in two cases. We found that an increase of the percent area of refractory tissue due to a prolongation of the wavelength seems to be particularly important. By automatic tracking of spiral tip movement we find that increased refractoriness resulted in rotor extinction caused by an increased spiral-tip meandering. We show that antiarrhythmic effects of IKur inhibitors are dependent on kinetic properties of blockade. We find that an increase of the percent area of refractory tissue is the underlying mechanism for an increased spiral-tip meandering, resulting in the extinction of re-entrant circuits. [ABSTRACT FROM AUTHOR]- Published
- 2013
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44. Altered HCN4 channel C-linker interaction is associated with familial tachycardia–bradycardia syndrome and atrial fibrillation.
- Author
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Duhme, Nana, Schweizer, Patrick A., Thomas, Dierk, Becker, Rüdiger, Schröter, Julian, Barends, Thomas R. M., Schlichting, Ilme, Draguhn, Andreas, Bruehl, Claus, Katus, Hugo A., and Koenen, Michael
- Abstract
Aims HCN4 channels are involved in generation, regulation, and stabilization of heart rhythm and channel dysfunction is associated with inherited sinus bradycardia. We asked whether dysfunctional HCN4 channels also contribute to the generation of cardiac tachyarrhythmias. Methods and results In a candidate gene approach, we screened 422 patients with atrial and/or ventricular tachyarrhythmias and detected a novel HCN4 gene mutation that replaced the positively charged lysine 530 with an asparagine (HCN4-K530N) in a highly conserved region of the C-linker. The index patient developed tachycardia–bradycardia syndrome and persistent atrial fibrillation (AF) in an age-dependent fashion. Pedigree analysis identified eight affected family members with a similar course of disease. Whole-cell patch clamp electrophysiology of HEK293 cells showed that homomeric mutant channels almost are indistinguishable from wild-type channels. In contrast, heteromeric channels composed of mutant and wild-type subunits displayed a significant hyperpolarizing shift in the half-maximal activation voltage. This may be caused by a shift in the equilibrium between the tonically inhibited nucleotide-free state of the C-terminal domain of HCN4 believed to consist of a ‘dimer of dimers’ and the activated ligand-bound tetrameric form, leading to an increased inhibition of activity in heteromeric channels. Conclusion Altered C-linker oligomerization in heteromeric channels is considered to promote familial tachycardia–bradycardia syndrome and persistent AF, indicating that f-channel dysfunction contributes to the development of atrial tachyarrhythmias. [ABSTRACT FROM PUBLISHER]
- Published
- 2013
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45. Suppression of persistent atrial fibrillation by genetic knockdown of caspase 3: a pre-clinical pilot study.
- Author
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Trappe, Kerstin, Thomas, Dierk, Bikou, Olympia, Kelemen, Kamilla, Lugenbiel, Patrick, Voss, Frederik, Becker, Rüdiger, Katus, Hugo A., and Bauer, Alexander
- Abstract
Aims Atrial fibrillation (AF) is linked to cardiomyocyte apoptosis, leading to atrial remodelling and reduction in electrical conduction velocity. We hypothesized that genetic suppression of an apoptotic key enzyme, caspase 3, would prevent the development of persistent AF by reducing apoptosis which may serve as an arrhythmogenic substrate. Methods and results Atrial fibrillation was induced in domestic pigs by atrial burst pacing via an implanted cardiac pacemaker. Study animals were then assigned to receive either Ad-siRNA-Cas3 gene therapy to inactivate caspase 3 or green fluorescent protein (Ad-GFP) as a control. Adenoviruses were applied using a hybrid technique employing right and left atrial virus injection followed by epicardial electroporation to increase expression of plasmid DNA. In pigs treated with Ad-siRNA-Cas3, the onset of AF was suppressed or significantly delayed compared with controls (10.3 ± 1.2 days vs. 6.0 ± 1.6 days; P= 0.04). Electrical mapping revealed prolonged atrial conduction in the control group that was prevented by Ad-siRNA-Cas3 gene therapy. On the molecular level, Ad-siRNA-Cas3 application resulted in down-regulation of caspase 3 expression and suppression of apoptotic activity. Conclusion Knockdown of caspase 3 by atrial Ad-siRNA-Cas3 gene transfer suppresses or delays the onset of persistent AF by reduction in apoptosis and prevention of intra-atrial conduction delay in a porcine model. These results highlight the significance of apoptosis in the pathophysiology of AF and demonstrate short-term efficacy of gene therapy for suppression of AF. [ABSTRACT FROM PUBLISHER]
- Published
- 2013
- Full Text
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46. Initial experience with robotic navigation for catheter ablation of paroxysmal and persistent atrial fibrillation.
- Author
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Thomas, Dierk, Scholz, Eberhard P., Schweizer, Patrick A., Katus, Hugo A., and Becker, Rüdiger
- Abstract
Abstract: Background and Purpose: Remote robotic navigation (RRN) technology has been developed to facilitate catheter ablation of symptomatic atrial fibrillation (AF). Here, we assess procedural parameters of AF ablation obtained during initial use of RRN compared with a control group treated with a manual ablation approach. Methods: Consecutive patients with symptomatic paroxysmal or persistent AF were subjected to radiofrequency catheter ablation with RRN (Sensei X [Hansen Medical, Mountain View, CA]; n = 25; mean age, 60 ± 2.3 years) or using the standard manual technique (n = 61; mean age, 62 ± 1.4 years). A circumferential pulmonary vein isolation approach guided by 3-dimensional electroanatomical mapping was followed. Results: Remote robotic navigation was associated with reduction of overall fluoroscopy time by 26%. In a case-control subgroup analysis comparing 25 patients with similar clinical characteristics from each group, mean fluoroscopy time was reduced by 22%. Acute isolation of pulmonary veins was achieved in 97% (RRN) and 96% (conventional ablation), respectively. Ablation times and frequency of adverse events were not significantly different among study groups. Conclusions: The early use of RRN resulted in a significant reduction of overall fluoroscopy time and was equally effective and safe compared with manual catheter ablation. [Copyright &y& Elsevier]
- Published
- 2012
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47. Genetic suppression of atrial fibrillation using a dominant-negative ether-a-go-go–related gene mutant.
- Author
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Soucek, Radim, Thomas, Dierk, Kelemen, Kamilla, Bikou, Olympia, Seyler, Claudia, Voss, Frederik, Becker, Rüdiger, Koenen, Michael, Katus, Hugo A., and Bauer, Alexander
- Abstract
Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Gene therapy–dependent modulation of atrial electrophysiology may provide a more specific alternative to pharmacological and ablative treatment strategies. Objective: We hypothesized that genetic inactivation of atrial repolarizing ether-a-go-go–related gene (ERG) K
+ currents using a dominant-negative mutant would provide rhythm control in AF. Methods: Ten domestic swine underwent pacemaker implantation and were subjected to atrial burst pacing to induce persistent AF. Animals were then randomized to receive either AdCERG-G627S to suppress ERG/IKr currents or green fluorescent protein (AdGFP) as control. Adenoviruses were applied using a novel hybrid technique combining atrial virus injection and epicardial electroporation to increase transgene expression. Results: In pigs treated with AdCERG-G627S, the onset of persistent AF was prevented (n = 2) or significantly delayed compared with AdGFP controls (12 ± 2.1 vs. 6.2 ± 1.3 days; P < .001) during 14-day follow-up. Effective refractory periods were prolonged in the AdCERG-G627S group compared with AdGFP animals (221.5 ± 4.7 ms vs. 197.0 ± 4.7 ms; P < .006). Impairment of left ventricular ejection fraction (LVEF) during AF was prevented by AdCERG-G627S application (LVEFCERG-G627S = 62.1% ± 4.0% vs. LVEFGFP = 30.3% ± 9.1%; P < .001). Conclusion: Inhibition of ERG function using atrial AdCERG-G627S gene transfer suppresses or delays the onset of persistent AF by prolongation of atrial refractoriness in a porcine model. Targeted gene therapy represents an alternative to pharmacological or ablative treatment of AF. [ABSTRACT FROM AUTHOR]- Published
- 2012
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48. Connexin 43 gene therapy prevents persistent atrial fibrillation in a porcine model.
- Author
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Bikou, Olympia, Thomas, Dierk, Trappe, Kerstin, Lugenbiel, Patrick, Kelemen, Kamilla, Koch, Martin, Soucek, Radim, Voss, Frederik, Becker, Rüdiger, Katus, Hugo A., and Bauer, Alexander
- Subjects
CONNEXINS ,GENE therapy ,ATRIAL fibrillation prevention ,PATHOLOGICAL physiology ,ARRHYTHMIA ,GENE expression ,HEART beat - Abstract
Aims Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and effective treatment of AF still remains an unmet medical need. AF is associated with atrial conduction disturbances caused by electrical and/or structural remodelling. We hypothesized that AF suppresses expression of the gap junction protein connexin (Cx) 43 and that Cx43 gene transfer to both atria would prevent persistent AF. The first aim of this study was to assess whether AF is associated with connexin remodelling in a porcine model. A strategy to suppress persistent AF by gene therapy was then developed and evaluated in vivo. Methods and results AF was induced in domestic pigs via atrial burst pacing, causing a 62.4% reduction in atrial Cx43 protein. Adenoviruses encoding for Cx43 (AdCx43) or green fluorescent protein (AdGFP) were injected into both atria, followed by epicardial electroporation to enhance transgene expression. Combining direct injection of adenoviruses with electroporation achieved GFP reporter gene expression in ∼50% of atrial cells in vivo. AdCx43-treated animals exhibited a 2.5-fold increase in atrial Cx43 protein content and did not develop persistent AF during the observation period of 14 days. In contrast, control animals developed persistent AF within 7.4 ± 0.5 days. Rapid ventricular heart rates during AF led to deterioration of cardiac function in control pigs but not in pigs treated with AdCx43. Conclusion Our results highlight the contribution of Cx43 to the pathophysiology of AF and demonstrate the viability of gene therapy for prevention of atrial arrhythmias. [ABSTRACT FROM PUBLISHER]
- Published
- 2011
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49. Asymptomatic pulmonary vein stenosis after cryoballoon catheter ablation of paroxysmal atrial fibrillation.
- Author
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Thomas, Dierk, Katus, Hugo A., and Voss, Frederik
- Abstract
Abstract: Pulmonary vein (PV) isolation is an effective treatment option for symptomatic atrial fibrillation. PV stenosis is a well-recognized complication of radiofrequency energy application but has not been observed following cryoballoon ablation. Here, we report a case of asymptomatic PV stenosis associated with cryoballoon PV isolation, illustrating a risk that should be considered when applying this technique. [Copyright &y& Elsevier]
- Published
- 2011
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50. The new selective IKs-blocking agent HMR 1556 restores sinus rhythm and prevents heart failure in pigs with persistent atrial fibrillation.
- Author
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Bauer, Alexander, Koch, Martin, Kraft, Patricia, Becker, Ruediger, Kelemen, Kamilla, Voss, Frederik, Senges, Julia C., Gerlach, Uwe, Katus, Hugo A., and Schoels, Wolfgang
- Subjects
MYOCARDIAL depressants ,ATRIAL fibrillation ,HEART failure ,LABORATORY swine ,PLACEBOS ,CARDIAC pacemakers - Abstract
Background Antiarrhythmic drugs for treatment of atrial fibrillation in patients with heart failure are limited by proarrhythmia and low efficacy. Experimental studies indicate that the pure I
Ks blocking agents chromanol 293b and HMR 1556 prolong repolarization more markedly at fast than at slow heart rates and during β-adrenergic stimulation. These properties may overcome some of the above quoted limitations. Methods and results Ten domestic swine underwent pacemaker implantation (PM) and atrial burst pacing to induce persistent AF. Four days after onset of persistent AP, pigs were randomized to HMR 1556 (30 mg/kg, p.o., 10 days) or placebo. AU animals receiving HMR 1556 converted to SR (5.2 ± 1.9 days), whereas placebo pigs remained in AF. Pigs treated with placebo developed high ventricular rates (297 ± 5 bpm) and severe heart failure, whereas pigs treated with HMR 1556 remained hemodynamicaily stable. Left ventricular ejection fraction on the day of euthanization was significantly lower in the placebo compared to the HMR 1556 group (30± 4% vs. 69± 5%,p <0.005). Similar results were seen with epinephrine levels (placebo 1563 ± 193 pmol/l vs. HMR 613 ± 196 pmol/l, p < 0.05). Right atrial monophasic action potentials were significantly longer in the HMR 1556 compared to the placebo group (230 ± 7 ms vs. 174 ± 13 ms, p < 0.05). Conclusions The new IKs blocker HMR 1556 efficiently and safely restores SR and prevents CHF in a model of persistent AF. Restoration of SR is most likely linked to a marked prolongation of atrial repolarization even at high heart rates. [ABSTRACT FROM AUTHOR]- Published
- 2005
- Full Text
- View/download PDF
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