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1. Prognostic impact of acute pulmonary triggers in patients with takotsubo syndrome: new insights from the International Takotsubo Registry

Author

Ken Kato, Victoria L. Cammann, L. Christian Napp, Konrad A. Szawan, Jozef Micek, Sara Dreiding, Rena A. Levinson, Vanya Petkova, Michael Würdinger, Alexandru Patrascu, Rafael Sumalinog, Sebastiano Gili, Christian F. Clarenbach, Malcolm Kohler, Manfred Wischnewsky, Rodolfo Citro, Carmine Vecchione, Eduardo Bossone, Michael Neuhaus, Jennifer Franke, Benjamin Meder, Milosz Jaguszewski, Michel Noutsias, Maike Knorr, Susanne Heiner, Fabrizio D'Ascenzo, Wolfgang Dichtl, Christof Burgdorf, Behrouz Kherad, Carsten Tschöpe, Annahita Sarcon, Jerold Shinbane, Lawrence Rajan, Guido Michels, Roman Pfister, Alessandro Cuneo, Claudius Jacobshagen, Mahir Karakas, Wolfgang Koenig, Alexander Pott, Philippe Meyer, Marco Roffi, Adrian Banning, Mathias Wolfrum, Florim Cuculi, Richard Kobza, Thomas A. Fischer, Tuija Vasankari, K.E. Juhani Airaksinen, Monika Budnik, Rafal Dworakowski, Philip MacCarthy, Christoph Kaiser, Stefan Osswald, Leonarda Galiuto, Christina Chan, Paul Bridgman, Daniel Beug, Clément Delmas, Olivier Lairez, Ekaterina Gilyarova, Alexandra Shilova, Mikhail Gilyarov, Ibrahim El‐Battrawy, Ibrahim Akin, Martin Kozel, Petr Tousek, David E. Winchester, Jan Galuszka, Christian Ukena, Gregor Poglajen, Pedro Carrilho‐Ferreira, Christian Hauck, Carla Paolini, Claudio Bilato, Masanori Sano, Iwao Ishibashi, Masayuki Takahara, Toshiharu Himi, Yoshio Kobayashi, Abhiram Prasad, Charanjit S. Rihal, Kan Liu, P. Christian Schulze, Matteo Bianco, Lucas Jörg, Hans Rickli, Gonçalo Pestana, Thanh H. Nguyen, Michael Böhm, Lars S. Maier, Fausto J. Pinto, Petr Widimský, Stephan B. Felix, Grzegorz Opolski, Ruediger C. Braun‐Dullaeus, Wolfgang Rottbauer, Gerd Hasenfuß, Burkert M. Pieske, Heribert Schunkert, Martin Borggrefe, Holger Thiele, Johann Bauersachs, Hugo A. Katus, John D. Horowitz, Carlo Di Mario, Thomas Münzel, Filippo Crea, Jeroen J. Bax, Thomas F. Lüscher, Frank Ruschitzka, Jelena R. Ghadri, and Christian Templin

Subjects
Takotsubo syndrome, Broken heart syndrome, Outcome, Acute respiratory insufficiency, Chronic obstructive pulmonary disease, InterTAK Registry, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Aims Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes. Methods and results Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In‐hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long‐term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long‐term mortality (hazard ratio 2.12, 95% confidence interval 1.33–3.38; P = 0.002). Conclusions The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in‐hospital course and a worse long‐term outcome.

Published
2021
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2. Altered limbic and autonomic processing supports brain-heart axis in Takotsubo syndrome

Author

Thomas F. Lüscher, Stjepan Jurisic, Carina Klein, Thierry Hiestand, Jürgen Hänggi, Christian Templin, Lutz Jäncke, Rena A. Levinson, Jelena-Rima Ghadri, and Marlene Sofie Topka

Subjects
Adult, Male, Hippocampus, 030204 cardiovascular system & hematology, Autonomic Nervous System, Amygdala, Ventricular Dysfunction, Left, 03 medical and health sciences, Catecholamines, 0302 clinical medicine, Limbic system, Takotsubo Cardiomyopathy, Limbic System, medicine, Humans, Default mode network, medicine.diagnostic_test, Resting state fMRI, business.industry, Brain, 030229 sport sciences, Magnetic Resonance Imaging, Autonomic nervous system, medicine.anatomical_structure, nervous system, Case-Control Studies, Female, Neural Networks, Computer, Cardiology and Cardiovascular Medicine, business, Functional magnetic resonance imaging, Insula, Neuroscience
Abstract

AIMS: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction often triggered by emotional or physical stress. Severe activation of the sympathetic nervous system with catecholamine release caused by a dysfunctional limbic system has been proposed as a potential mechanism. We hypothesize that brain regions responsible for autonomic integration and/or limbic processing might be involved in the development of TTS. Here, we investigated alterations in resting state functional connectivity in TTS patients compared with healthy controls. METHODS AND RESULTS: Using brain functional magnetic resonance imaging (fMRI), resting state functional connectivity has been assessed in 15 subjects with TTS and 39 healthy controls. Network-based statistical analyses were conducted to identify subnetworks with altered resting state functional connectivity. Sympathetic and parasympathetic networks have been constructed in addition to the default mode network and whole-brain network. We found parasympathetic- and sympathetic-associated subnetworks both showing reduced resting state functional connectivity in TTS patients compared with controls. Important brain regions constituting parasympathetic- and sympathetic-associated subnetworks included the amygdala, hippocampus, and insula as well as cingulate, parietal, temporal, and cerebellar regions. Additionally, the default mode network as well as limbic regions in the whole-brain analysis demonstrated reduced resting state functional connectivity in TTS, including the hippocampus, parahippocampal, and medial prefrontal regions. CONCLUSION: For the first time, we demonstrate hypoconnectivity of central brain regions associated with autonomic functions and regulation of the limbic system in patients with TTS. These findings suggest that autonomic-limbic integration might play an important role in the pathophysiology and contribute to the understanding of TTS.

Published
2019
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3. Ethnic comparison in takotsubo syndrome

Author

Stefan Osswald, Yasuhiro Tomita, Yoichi Imori, Christian Templin, Jerold S. Shinbane, Petr Widimský, Wolfgang Dichtl, Maike Knorr, Petr Tousek, Olivier Lairez, Iwao Ishibashi, Tetsuo Yamaguchi, Frank Ruschitzka, Johann Bauersachs, Sebastiano Gili, Toshiaki Isogai, Jelena R. Ghadri, Roman Pfister, Florim Cuculi, Thomas Münzel, Victoria L. Cammann, Hugo A. Katus, Pedro Carrilho-Ferreira, Hitoshi Takano, Paul Bridgman, Wolfgang Koenig, Annahita Sarcon, Tsutomu Murakami, Christof Burgdorf, Wolfgang Rottbauer, Ibrahim Akin, Rodolfo Citro, John D. Horowitz, Philip MacCarthy, Reiko Shiomura, Michel Noutsias, Stephan B. Felix, Fausto J. Pinto, Adrian P. Banning, Yoshio Kobayashi, Thomas F. Lüscher, Martin Borggrefe, Ioana Sorici-Barb, Monika Budnik, Lucas Jörg, Thomas Jansen, Abhiram Prasad, Carlo Di Mario, Alexander Pott, Rafal Dworakowski, Kan Liu, Akihisa Kimura, Lawrence Rajan, Konrad A. Szawan, Christian Hauck, Vanya Petkova, Shingo Mizuno, Christina Chan, Rena A. Levinson, Claudius Jacobshagen, Lars S. Maier, Richard Kobza, Masaki Wakita, Jan Galuszka, Fabrizio D'Ascenzo, Gerd Hasenfuß, Shunichi Nakamura, Philippe Meyer, Mikhail Gilyarov, Ruediger C. Braun-Dullaeus, Michael Böhm, Alexandra Shilova, Jeroen J. Bax, Davide Di Vece, K.E. Juhani Airaksinen, David Niederseer, Alessandro Cuneo, Jennifer Franke, Michael Neuhaus, Heribert Schunkert, Samir M. Said, Jose David Arroja, Hiroki Mochizuki, Mahir Karakas, Maximilian Schönberger, David E. Winchester, Daniel Beug, Thomas Fischer, Matteo Bianco, Carsten Tschöpe, Filippo Crea, Michael Würdinger, Guido Michels, Burkhardt Seifert, Ekaterina Gilyarova, Leonarda Galiuto, Wataru Shimizu, Burkert Pieske, Grzegorz Opolski, L. Christian Napp, Holger Thiele, Charanjit S. Rihal, Christian Ukena, Susanne Heiner, Christoph Kaiser, Noriko Suzuki, Clément Delmas, Shigeru Saito, Manfred Wischnewsky, Klaus Empen, Sara Dreiding, Hans Rickli, Claudio Bilato, Tuija Vasankari, Toshiharu Himi, Ibrahim El-Battrawy, Behrouz Kherad, Yuji Ikari, Ken Kato, Martin Kozel, Eduardo Bossone, Gregor Poglajen, Miłosz Jaguszewski, Carla Paolini, and Repositório da Universidade de Lisboa

Subjects
Male, medicine.medical_specialty, Prognostic factor, Race, Ethnic group, Shock, Cardiogenic, Disease, 030204 cardiovascular system & hematology, Broken heart syndrome, White People, 03 medical and health sciences, 0302 clinical medicine, Asian People, Japan, Takotsubo Cardiomyopathy, Internal medicine, medicine, Prevalence, Ethnicity, Humans, 030212 general & internal medicine, Hospital Mortality, Registries, Aged, Takotsubo syndrome, business.industry, Cardiogenic shock, General Medicine, Health Status Disparities, Middle Aged, medicine.disease, ddc, Europe, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/., Background: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes. Methods: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients. Results: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients. Conclusion: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers., Open Access funding provided by Universität Zürich. CT has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme and the Swiss Heart Foundation. L.S.M. has been supported by EU HORIZON 2020 (SILICOFCM ID777204). J.R.G has received a grant “Filling the gap” from the University of Zurich. The InterTAK Registry is supported by The Biss Davies Charitable Trust.

Published
2021

4. Prognostic impact of acute pulmonary triggers in patients with Takotsubo syndrome : new insights from the International Takotsubo Registry

Author

Wolfgang Koenig, John D. Horowitz, Hugo A. Katus, Paul Bridgman, Abhiram Prasad, Carlo Di Mario, Alessandro Cuneo, Johann Bauersachs, Jeroen J. Bax, Mathias Wolfrum, Carsten Tschöpe, Masanori Sano, Vanya Petkova, Lucas Jörg, Fausto J. Pinto, Petr Widimský, Masayuki Takahara, Rodolfo Citro, Iwao Ishibashi, Frank Ruschitzka, Thomas Münzel, Carmine Vecchione, Wolfgang Dichtl, Jan Galuszka, Kan Liu, Leonarda Galiuto, Grzegorz Opolski, Jozef Micek, Susanne Heiner, Florim Cuculi, Gerd Hasenfuß, Jerold S. Shinbane, Maike Knorr, Sebastiano Gili, Filippo Crea, Michael Würdinger, Alexandra Shilova, Malcolm Kohler, Lawrence Rajan, Christian F Clarenbach, Rena A. Levinson, Mikhail Gilyarov, Alexander Pott, Roman Pfister, Ekaterina Gilyarova, Claudius Jacobshagen, Adrian P. Banning, Michael Neuhaus, Jennifer Franke, Christian Templin, Christof Burgdorf, Daniel Beug, K.E. Juhani Airaksinen, Victoria L. Cammann, Thanh H Nguyen, Rafael Sumalinog, Monika Budnik, Wolfgang Rottbauer, Yoshio Kobayashi, Petr Tousek, Stephan B. Felix, Marco Roffi, Michael Böhm, Konrad A. Szawan, Toshiharu Himi, Ibrahim Akin, Christina Chan, Thomas F. Lüscher, Rafal Dworakowski, Annahita Sarcon, Ibrahim El-Battrawy, Miłosz Jaguszewski, Alexandru Patrascu, Eduardo Bossone, David E. Winchester, Michel Noutsias, Guido Michels, Gregor Poglajen, Christian Hauck, Fabrizio D'Ascenzo, Burkert Pieske, Christian Ukena, Thomas Fischer, Matteo Bianco, Lars S. Maier, Christoph Kaiser, Philippe Meyer, P. Christian Schulze, Behrouz Kherad, Gonçalo Pestana, Claudio Bilato, Ken Kato, Martin Kozel, Charanjit S. Rihal, Clément Delmas, Stefan Osswald, Olivier Lairez, Jelena R. Ghadri, Martin Borggrefe, Philip MacCarthy, Heribert Schunkert, Manfred Wischnewsky, Sara Dreiding, Hans Rickli, Tuija Vasankari, L. Christian Napp, Holger Thiele, Richard Kobza, Carla Paolini, Benjamin Meder, Mahir Karakas, Pedro Carrilho-Ferreira, Ruediger C. Braun-Dullaeus, Kato, K., Cammann, V. L., Napp, L. C., Szawan, K. A., Micek, J., Dreiding, S., Levinson, R. A., Petkova, V., Wurdinger, M., Patrascu, A., Sumalinog, R., Gili, S., Clarenbach, C. F., Kohler, M., Wischnewsky, M., Citro, R., Vecchione, C., Bossone, E., Neuhaus, M., Franke, J., Meder, B., Jaguszewski, M., Noutsias, M., Knorr, M., Heiner, S., D'Ascenzo, F., Dichtl, W., Burgdorf, C., Kherad, B., Tschope, C., Sarcon, A., Shinbane, J., Rajan, L., Michels, G., Pfister, R., Cuneo, A., Jacobshagen, C., Karakas, M., Koenig, W., Pott, A., Meyer, P., Roffi, M., Banning, A., Wolfrum, M., Cuculi, F., Kobza, R., Fischer, T. A., Vasankari, T., Airaksinen, K. E. J., Budnik, M., Dworakowski, R., Maccarthy, P., Kaiser, C., Osswald, S., Galiuto, L., Chan, C., Bridgman, P., Beug, D., Delmas, C., Lairez, O., Gilyarova, E., Shilova, A., Gilyarov, M., El-Battrawy, I., Akin, I., Kozel, M., Tousek, P., Winchester, D. E., Galuszka, J., Ukena, C., Poglajen, G., Carrilho-Ferreira, P., Hauck, C., Paolini, C., Bilato, C., Sano, M., Ishibashi, I., Takahara, M., Himi, T., Kobayashi, Y., Prasad, A., Rihal, C. S., Liu, K., Schulze, P. C., Bianco, M., Jorg, L., Rickli, H., Pestana, G., Nguyen, T. H., Bohm, M., Maier, L. S., Pinto, F. J., Widimsky, P., Felix, S. B., Opolski, G., Braun-Dullaeus, R. C., Rottbauer, W., Hasenfuss, G., Pieske, B. M., Schunkert, H., Borggrefe, M., Thiele, H., Bauersachs, J., Katus, H. A., Horowitz, J. D., Di Mario, C., Munzel, T., Crea, F., Bax, J. J., Luscher, T. F., Ruschitzka, F., Ghadri, J. R., Templin, C., and Repositório da Universidade de Lisboa

Subjects
medicine.medical_specialty, Acute respiratory insufficiency, acute respiratory insufficiency, Shock, Cardiogenic, 030204 cardiovascular system & hematology, Broken heart syndrome, chronic obstructive pulmonary disease, 03 medical and health sciences, 0302 clinical medicine, Takotsubo Cardiomyopathy, Original Research Articles, Internal medicine, medicine, Humans, Diseases of the circulatory (Cardiovascular) system, takotsubo syndrome, Registries, Original Research Article, 030212 general & internal medicine, Survival analysis, Outcome, Takotsubo syndrome, intertak registry, business.industry, InterTAK Registry, Incidence (epidemiology), Cardiogenic shock, Chronic obstructive pulmonary disease, Hazard ratio, broken heart syndrome, Shock, Cardiogenic, Prognosis, medicine.disease, Survival Analysis, outcome, Confidence interval, 3. Good health, RC666-701, Heart failure, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Cardiology and Cardiovascular Medicine, business
Abstract

© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License., Aims: Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes. Methods and results: Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In-hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long-term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long-term mortality (hazard ratio 2.12, 95% confidence interval 1.33-3.38; P = 0.002). Conclusions: The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in-hospital course and a worse long-term outcome., C. T. has been supported by the H.H. Sheikh Khalifa binHamad Al-Thani Research Programme and the Swiss HeartFoundation. The InterTAK Registry is supported by the BissDavies Charitable Trust. L. S. M. has been supported by EUHORIZON 2020(SILICOFCM ID777204)

Published
2021

5. Long-Term Prognosis of Patients With Takotsubo Syndrome

Author

John D. Horowitz, Thomas Münzel, David E. Winchester, Guido Michels, Katharina J. Ding, Wolfgang Koenig, Jeroen J. Bax, Burkert Pieske, Mahir Karakas, Christian Ukena, K.E. Juhani Airaksinen, Christoph Kaiser, Sebastiano Gili, Stephan B. Felix, Rafal Dworakowski, Christian Templin, Claudius Jacobshagen, Abhiram Prasad, Fabrizio D'Ascenzo, Lawrence Rajan, Martin Borggrefe, Rena A. Levinson, Christof Burgdorf, Florim Cuculi, Petr Tousek, Thomas F. Lüscher, Alexandra Shilova, Mikhail Gilyarov, Victoria L. Cammann, Roman Pfister, Frank Ruschitzka, Alessandro Candreva, Filippo Crea, Davide Di Vece, Wolfgang Rottbauer, Ruediger C. Braun-Dullaeus, Heribert Schunkert, Carsten Tschöpe, Stefan Osswald, Rodolfo Citro, Burkhardt Seifert, Annahita Sarcon, Ibrahim Akin, Gerd Hasenfuß, Leonarda Galiuto, L. Christian Napp, Holger Thiele, Ekaterina Gilyarova, Grzegorz Opolski, Susanne Heiner, Michel Noutsias, Johann Bauersachs, Miłosz Jaguszewski, Alessandro Cuneo, Hugo A. Katus, Olivier Lairez, Ibrahim El-Battrawy, Wolfgang Dichtl, Jozef Micek, Philip MacCarthy, Rahel Bianchi, Maike Knorr, Ken Kato, Adrian P. Banning, Jelena-R. Ghadri, Martin Kozel, Michael Böhm, Konrad A. Szawan, Jennifer Franke, Manfred Wischnewsky, Klaus Empen, Tuija Vasankari, Eduardo Bossone, Richard Kobza, Beatrice Bacchi, Susanne A. Schlossbauer, Petr Widimský, Stjepan Jurisic, Samir M. Said, Thomas Fischer, Clément Delmas, Ghadri, Jr, Kato, K, Cammann, Vl, Gili, S, Jurisic, S, Di Vece, D, Candreva, A, Ding, Kj, Micek, J, Szawan, Ka, Bacchi, B, Bianchi, R, Levinson, Ra, Wischnewsky, M, Seifert, B, Schlossbauer, Sa, Citro, R, Bossone, E, Munzel, T, Knorr, M, Heiner, S, D'Ascenzo, F, Franke, J, Sarcon, A, Napp, Lc, Jaguszewski, M, Noutsias, M, Katus, Ha, Burgdorf, C, Schunkert, H, Thiele, H, Bauersachs, J, Tschope, C, Pieske, Bm, Rajan, L, Michels, G, Pfister, R, Cuneo, A, Jacobshagen, C, Hasenfuss, G, Karakas, M, Koenig, W, Rottbauer, W, Said, Sm, Braun-Dullaeus, Rc, Banning, A, Cuculi, F, Kobza, R, Fischer, Ta, Vasankari, T, Airaksinen, Kej, Opolski, G, Dworakowski, R, Maccarthy, P, Kaiser, C, Osswald, S, Galiuto, L, Crea, F, Dichtl, W, Empen, K, Felix, Sb, Delmas, C, Lairez, O, El-Battrawy, I, Akin, I, Borggrefe, M, Horowitz, J, Kozel, M, Tousek, P, Widimsky, P, Gilyarova, E, Shilova, A, Gilyarov, M, Winchester, De, Ukena, C, Bax, Jj, Prasad, A, Bohm, M, Luscher, Tf, Ruschitzka, F, and Templin, C

Subjects
Male, Acute coronary syndrome, medicine.medical_specialty, Time Factors, 030204 cardiovascular system & hematology, tako tsubo syndrome, acute coronary syndrome, broken heart syndrome, classification, outcome, stress factor, Broken heart syndrome, 03 medical and health sciences, 0302 clinical medicine, Takotsubo Cardiomyopathy, Internal medicine, medicine, Humans, Registries, 030212 general & internal medicine, Mortality, Aged, Aged, 80 and over, Takotsubo syndrome, business.industry, Mortality rate, Electroencephalography, Emotional stress, Middle Aged, ta3121, Prognosis, Stress factor, medicine.disease, 3. Good health, Physical stress, Cardiology and Cardiovascular Medicine, Cohort, Female, Nervous System Diseases, business, Stress, Psychological, Follow-Up Studies
Abstract

Background Prognosis of Takotsubo syndrome (TTS) remains controversial due to scarcity of available data. Additionally, the effect of the triggering factors remains elusive. Objectives This study compared prognosis between TTS and acute coronary syndrome (ACS) patients and investigated short- and long-term outcomes in TTS based on different triggers. Methods Patients with TTS were enrolled from the International Takotsubo Registry. Long-term mortality of patients with TTS was compared to an age- and sex-matched cohort of patients with ACS. In addition, short- and long-term outcomes were compared between different groups according to triggering conditions. Results Overall, TTS patients had a comparable long-term mortality risk with ACS patients. Of 1,613 TTS patients, an emotional trigger was detected in 485 patients (30%). Of 630 patients (39%) related to physical triggers, 98 patients (6%) had acute neurologic disorders, while in the other 532 patients (33%), physical activities, medical conditions, or procedures were the triggering conditions. The remaining 498 patients (31%) had no identifiable trigger. TTS patients related to physical stress showed higher mortality rates than ACS patients during long-term follow-up, whereas patients related to emotional stress had better outcomes compared with ACS patients. Conclusions Overall, TTS patients had long-term outcomes comparable to age- and sex-matched ACS patients. Also, we demonstrated that TTS can either be benign or a life-threating condition depending on the inciting stress factor. We propose a new classification based on triggers, which can serve as a clinical tool to predict short- and long-term outcomes of TTS. (International Takotsubo Registry [InterTAK Registry]; NCT01947621)

Published
2018

6. Impact of aspirin on takotsubo syndrome: a propensity score-based analysis of the InterTAK Registry

Author

Christian Templin, Antonio H. Frangieh, John D. Horowitz, Rodolfo Citro, Johann Bauersachs, Petr Widimský, Philip MacCarthy, David E. Winchester, Andrea Saglietto, Alessandro Cuneo, Guido Michels, Ekaterina Gilyarova, Burkert Pieske, Christian Ukena, Frank Ruschitzka, Christoph Kaiser, Mauro Gasparini, Mario Iannaccone, Wolfgang Koenig, Eduardo Bossone, Gaetano M. De Ferrari, Miłosz Jaguszewski, Florim Cuculi, Jeroen J. Bax, Wolfgang-Michael Franz, Leonarda Galiuto, L. Christian Napp, Grzegorz Opolski, Holger Thiele, Susanne Heiner, Abhiram Prasad, Carlo Di Mario, Stephan B. Felix, Thomas Münzel, Margherita Annaratone, Roman Pfister, Thomas F. Lüscher, Adrian P. Banning, Ruediger C. Braun-Dullaeus, Konrad A. Szawan, K.E. Juhani Airaksinen, Mahir Karakas, Michael Böhm, Victoria L. Cammann, Gerd Hasenfuß, Wolfgang Rottbauer, Rena A. Levinson, Samir M. Said, Ibrahim Akin, Fabrizio D'Ascenzo, Lawrence Rajan, Maike Knorr, Thomas Fischer, Rafal Dworakowski, Mikhail Gilyarov, Maurizio Bertaina, Annahita Sarcon, Mauro Rinaldi, Ken Kato, Martin Kozel, Wolfgang Dichtl, Carsten Tschöpe, Hugo A. Katus, Filippo Crea, Clément Delmas, Jennifer Franke, Giuseppe Biondi-Zoccai, Claudius Jacobshagen, Ibrahim El-Battrawy, Alexandra Shilova, Sebastiano Gili, Davide Di Vece, Beatrice Boffini, Michael Neuhaus, Christof Burgdorf, Petr Tousek, Jelena R. Ghadri, Martin Borggrefe, Stefan Osswald, Olivier Lairez, Richard Kobza, Heribert Schunkert, Klaus Empen, Tuija Vasankari, Michel Noutsias, D'Ascenzo, F., Gili, S., Bertaina, M., Iannaccone, M., Cammann, V. L., Di Vece, D., Kato, K., Saglietto, A., Szawan, K. A., Frangieh, A. H., Boffini, B., Annaratone, M., Sarcon, A., Levinson, R. A., Franke, J., Napp, L. C., Jaguszewski, M., Noutsias, M., Munzel, T., Knorr, M., Heiner, S., Katus, H. A., Burgdorf, C., Schunkert, H., Thiele, H., Bauersachs, J., Tschope, C., Pieske, B. M., Rajan, L., Michels, G., Pfister, R., Cuneo, A., Jacobshagen, C., Hasenfuss, G., Karakas, M., Koenig, W., Rottbauer, W., Said, S. M., Braun-Dullaeus, R. C., Banning, A., Cuculi, F., Kobza, R., Fischer, T. A., Vasankari, T., Airaksinen, K. E. J., Opolski, G., Dworakowski, R., Maccarthy, P., Kaiser, C., Osswald, S., Galiuto, L., Crea, F., Dichtl, W., Franz, W. M., Empen, K., Felix, S. B., Delmas, C., Lairez, O., El-Battrawy, I., Akin, I., Borggrefe, M., Horowitz, J. D., Kozel, M., Tousek, P., Widimsky, P., Gilyarova, E., Shilova, A., Gilyarov, M., Biondi-Zoccai, G., Winchester, D. E., Ukena, C., Neuhaus, M., Bax, J. J., Prasad, A., Di Mario, C., Bohm, M., Gasparini, M., Ruschitzka, F., Bossone, E., Citro, R., Rinaldi, M., De Ferrari, G. M., Luscher, T., Ghadri, J. R., and Templin, C.

Subjects
medicine.medical_specialty, Medical therapy, Acute heart failure, Aspirin, Outcome, Takotsubo syndrome, Myocardial Infarction, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Recurrence, Takotsubo Cardiomyopathy, law, Internal medicine, medicine, Humans, Registries, Myocardial infarction, Propensity Score, Stroke, Heart Failure, business.industry, Hazard ratio, medicine.disease, Confidence interval, 3. Good health, Treatment Outcome, Ischemic Attack, Transient, Heart failure, Propensity score matching, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Cardiology, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

Aims The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS). Methods and results Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50-3.04, P = 0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78-1.58, P = 0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting. Conclusion In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621.

Published
2020

7. Cardiac arrest in takotsubo syndrome: results from the InterTAK Registry

Author

David E. Winchester, Philip MacCarthy, Leonarda Galiuto, Guido Michels, Hugo A. Katus, Grzegorz Opolski, Susanne Heiner, Burkert Pieske, Christian Ukena, Wolfgang Koenig, Richard Kobza, Sebastiano Gili, Christoph Kaiser, Eduardo Bossone, Beatrice Bacchi, Johann Bauersachs, Filippo Crea, K.E. Juhani Airaksinen, Konrad A. Szawan, Heribert Schunkert, Abhiram Prasad, Carlo Di Mario, John D. Horowitz, L. Christian Napp, Holger Thiele, Gerd Hasenfuß, Rafal Dworakowski, Ekaterina Gilyarova, Roman Pfister, Christof Burgdorf, Christian Templin, Flurina Famos, Stjepan Jurisic, Victoria L. Cammann, Stefan Osswald, Miłosz Jaguszewski, Maike Knorr, Wolfgang Rottbauer, Alexandra Shilova, Ibrahim Akin, Petr Tousek, Jeroen J. Bax, Adrian P. Banning, Lawrence Rajan, Alessandro Cuneo, Davide Di Vece, Claudius Jacobshagen, Katharina J. Ding, Susanne A. Schlossbauer, Jennifer Franke, Ruediger C. Braun-Dullaeus, Manfred Wischnewsky, Klaus Empen, Michael Böhm, Carsten Tschöpe, Petr Widimský, Stephan B. Felix, Olivier Lairez, Burkhardt Seifert, Thomas Münzel, Michel Noutsias, Tuija Vasankari, Thomas F. Lüscher, Ibrahim El-Battrawy, Slayman Obeid, Fabrizio D'Ascenzo, Florim Cuculi, Mikhail Gilyarov, Rodolfo Citro, Mahir Karakas, Ken Kato, Jozef Micek, Fiorenzo Gaita, Martin Kozel, Wolfgang Dichtl, Clément Delmas, Rena A. Levinson, Samir M. Said, Olivia Lenoir, Annahita Sarcon, Thomas Fischer, Jelena R. Ghadri, Martin Borggrefe, Frank Ruschitzka, Gili, S, Cammann, Vl, Schlossbauer, Sa, Kato, K, D'Ascenzo, F, Di Vece, D, Jurisic, S, Micek, J, Obeid, S, Bacchi, B, Szawan, Ka, Famos, F, Sarcon, A, Levinson, R, Ding, Kj, Seifert, B, Lenoir, O, Bossone, E, Citro, R, Franke, J, Napp, Lc, Jaguszewski, M, Noutsias, M, Munzel, T, Knorr, M, Heiner, S, Katus, Ha, Burgdorf, C, Schunkert, H, Thiele, H, Bauersachs, J, Tschope, C, Pieske, Bm, Rajan, L, Michels, G, Pfister, R, Cuneo, A, Jacobshagen, C, Hasenfuss, G, Karakas, M, Koenig, W, Rottbauer, W, Said, Sm, Braun-Dullaeus, Rc, Banning, A, Cuculi, F, Kobza, R, Fischer, Ta, Vasankari, T, Airaksinen, Kej, Opolski, G, Dworakowski, R, Maccarthy, P, Kaiser, C, Osswald, S, Galiuto, L, Crea, F, Dichtl, W, Empen, K, Felix, Sb, Delmas, C, Lairez, O, El-Battrawy, I, Akin, I, Borggrefe, M, Gilyarova, E, Shilova, A, Gilyarov, M, Horowitz, Jd, Kozel, M, Tousek, P, Widimsky, P, Winchester, De, Ukena, C, Gaita, F, Di Mario, C, Wischnewsky, Mb, Bax, Jj, Prasad, A, Bohm, M, Ruschitzka, F, Luscher, Tf, Ghadri, Jr, and Templin, C

Subjects
Male, Tachycardia, Acute heart failure, Broken heart syndrome, Cardiac arrest, Outcome, Takotsubo syndrome, medicine.medical_specialty, Cardiomyopathy, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Takotsubo Cardiomyopathy, Internal medicine, Humans, Medicine, Registries, 030212 general & internal medicine, Asystole, Retrospective Studies, Ejection fraction, business.industry, Atrial fibrillation, Middle Aged, Prognosis, medicine.disease, Survival Analysis, ddc, Heart Arrest, 3. Good health, Editor's Choice, Editorial, Pulseless electrical activity, Ventricular fibrillation, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract

Aims We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS). Methods and results We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P Conclusions Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.

Published
2019

9. Age -Related Variations in Takotsubo Syndrome

Author

Behrouz Kherad, Roman Pfister, Ken Kato, Stefan Osswald, Thanh H Nguyen, Benjamin Meder, Alessandro Cuneo, Toshiharu Himi, Stephan B. Felix, Marco Roffi, Lawrence Rajan, Thomas F. Lüscher, David E. Winchester, Sebastiano Gili, Gerd Hasenfuß, Guido Michels, Ibrahim El-Battrawy, Petr Widimský, Olivier Lairez, Victoria L. Cammann, Rafal Dworakowski, Eduardo Bossone, Mahir Karakas, Charanjit S. Rihal, Burkert Pieske, Barbara E. Stähli, Gregor Poglajen, Wolfgang Rottbauer, Leonarda Galiuto, Grzegorz Opolski, Christian Ukena, Susanne Heiner, Christoph Kaiser, Christian Hauck, Filippo Crea, Wolfgang Koenig, Ibrahim Akin, Christof Burgdorf, Carsten Tschöpe, Clément Delmas, Yoshio Kobayashi, K.E. Juhani Airaksinen, Florim Cuculi, Mikhail Gilyarov, Pedro Carrilho-Ferreira, Masayuki Takahara, Ali Al-Shammari, Christina Chan, Jerold S. Shinbane, Miłosz Jaguszewski, Hugo A. Katus, Fabrizio D'Ascenzo, Wolfgang Dichtl, Jehangir Din, Paul Bridgman, John D. Horowitz, Toshihiro Shoji, Jan Galuszka, Monika Budnik, Claudio Bilato, Jelena R. Ghadri, Alexander Pott, Christian Templin, Konrad A. Szawan, Claudius Jacobshagen, Ruediger C. Braun-Dullaeus, Gonçalo Pestana, Abhiram Prasad, Carlo Di Mario, Fausto J. Pinto, Maike Knorr, Iwao Ishibashi, Thomas Münzel, Lars S. Maier, Jennifer Franke, Mathias Wolfrum, Adrian P. Banning, Philippe Meyer, Kan Liu, Alexandra Shilova, Davide Di Vece, Daniel Beug, Michael Neuhaus, Martin Borggrefe, Michael Böhm, Annahita Sarcon, Heribert Schunkert, Petr Tousek, Rena A. Levinson, Ekaterina Gilyarova, Frank Ruschitzka, Carla Paolini, Michel Noutsias, Richard Kobza, Thomas Fischer, Matteo Bianco, P. Christian Schulze, Lucas Jörg, Manfred Wischnewsky, Sara Dreiding, Hans Rickli, Tuija Vasankari, Rodolfo Citro, Jeroen J. Bax, Philip MacCarthy, L. Christian Napp, Holger Thiele, Karolina Polednikova, Johann Bauersachs, Repositório da Universidade de Lisboa, Cammann, V. L., Szawan, K. A., Stahli, B. E., Kato, K., Budnik, M., Wischnewsky, M., Dreiding, S., Levinson, R. A., Di Vece, D., Gili, S., Citro, R., Bossone, E., Neuhaus, M., Franke, J., Meder, B., Jaguszewski, M., Noutsias, M., Knorr, M., Heiner, S., D'Ascenzo, F., Dichtl, W., Burgdorf, C., Kherad, B., Tschope, C., Sarcon, A., Shinbane, J., Rajan, L., Michels, G., Pfister, R., Cuneo, A., Jacobshagen, C., Karakas, M., Koenig, W., Pott, A., Meyer, P., Roffi, M., Banning, A., Wolfrum, M., Cuculi, F., Kobza, R., Fischer, T. A., Vasankari, T., Airaksinen, K. E. J., Napp, L. C., Dworakowski, R., Maccarthy, P., Kaiser, C., Osswald, S., Galiuto, L., Chan, C., Bridgman, P., Beug, D., Delmas, C., Lairez, O., Gilyarova, E., Shilova, A., Gilyarov, M., El-Battrawy, I., Akin, I., Polednikova, K., Tousek, P., Winchester, D. E., Galuszka, J., Ukena, C., Poglajen, G., Carrilho-Ferreira, P., Hauck, C., Paolini, C., Bilato, C., Kobayashi, Y., Shoji, T., Ishibashi, I., Takahara, M., Himi, T., Din, J., Al-Shammari, A., Prasad, A., Rihal, C. S., Liu, K., Schulze, P. C., Bianco, M., Jorg, L., Rickli, H., Pestana, G., Nguyen, T. H., Bohm, M., Maier, L. S., Pinto, F. J., Widimsky, P., Felix, S. B., Braun-Dullaeus, R. C., Rottbauer, W., Hasenfuss, G., Pieske, B. M., Schunkert, H., Borggrefe, M., Thiele, H., Bauersachs, J., Katus, H. A., Horowitz, J. D., Di Mario, C., Munzel, T., Crea, F., Bax, J. J., Luscher, T. F., Ruschitzka, F., Ghadri, J. R., Opolski, G., and Templin, C.

Subjects
Male, Pediatrics, medicine.medical_specialty, Shock, Cardiogenic, Hospital mortality, 030204 cardiovascular system & hematology, age, broken heart syndrome, outcome, takotsubo syndrome, Global Health, Risk Assessment, Broken heart syndrome, 03 medical and health sciences, 0302 clinical medicine, Age, Takotsubo Cardiomyopathy, Intensive care, Age related, Prevalence, Medicine, Humans, 030212 general & internal medicine, Registries, Hospital Mortality, Mortality, Age of Onset, Aged, Outcome, Takotsubo syndrome, business.industry, Mental Disorders, Age Factors, Shock, Middle Aged, medicine.disease, Prognosis, Cardiogenic, 3. Good health, Causality, Baseline characteristics, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Female, Age of onset, Nervous System Diseases, Cardiology and Cardiovascular Medicine, business
Abstract

© 2020 by the American College of Cardiology Foundation., BACKGROUND: Takotsubo syndrome (TTS) occurs predominantly in post-menopausal women but is also found in younger patients. OBJECTIVES: This study aimed to investigate age-related differences in TTS. METHODS: Patients diagnosed with TTS and enrolled in the International Takotsubo Registry between January 2011 and February 2017 were included in this analysis and were stratified by age (younger: #50 years, middle-age: 51 to 74 years, elderly: $75 years). Baseline characteristics, hospital course, as well as short- and long-term mortality were compared among groups. RESULTS Of 2,098 TTS patients, 242 (11.5%) patients were #50 years of age, 1,194 (56.9%) were 51 to 74 years of age, and 662 (31.6%) were $75 years of age. Younger patients were more often men (12.4% vs. 10.9% vs. 6.3%; p ¼ 0.002) and had an increased prevalence of acute neurological (16.3% vs. 8.4% vs. 8.8%; p ¼ 0.001) or psychiatric disorders (14.1% vs. 10.3% vs. 5.6%; p < 0.001) compared with middle-aged and elderly TTS patients. Furthermore, younger patients had more often cardiogenic shock (15.3% vs. 9.1% vs. 8.1%; p ¼ 0.004) and had a numerically higher in-hospital mortality (6.6% vs. 3.6% vs. 5.1%; p ¼ 0.07). At multivariable analysis, younger (odds ratio: 1.60; 95% confidence interval: 0.86 to 3.01; p ¼ 0.14) and older age (odds ratio: 1.09; 95% confidence interval: 0.66 to 1.80; p ¼ 0.75) were not independently associated with in-hospital mortality using the middle-aged group as a reference. There were no differences in 60-day mortality rates among groups. CONCLUSIONS: A substantial proportion of TTS patients are younger than 50 years of age. TTS is associated with severe complications requiring intensive care, particularly in younger patients.

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