Author + information
- Received March 28, 2018
- Revision received June 5, 2018
- Accepted June 5, 2018
- Published online August 13, 2018.
- Jelena R. Ghadri, MDa,∗,
- Ken Kato, MD, PhDa,∗,
- Victoria L. Cammanna,
- Sebastiano Gili, MDa,b,
- Stjepan Jurisic, MDa,
- Davide Di Vece, MDa,
- Alessandro Candreva, MDa,
- Katharina J. Dinga,
- Jozef Miceka,
- Konrad A. Szawana,
- Beatrice Bacchia,
- Rahel Bianchia,
- Rena A. Levinsona,c,
- Manfred Wischnewsky, PhDd,
- Burkhardt Seifert, PhDe,
- Susanne A. Schlossbauer, MDa,
- Rodolfo Citro, MD, PhDf,
- Eduardo Bossone, MD, PhDf,
- Thomas Münzel, MDg,
- Maike Knorr, MDg,
- Susanne Heiner, MDg,
- Fabrizio D’Ascenzo, MD, PhDb,
- Jennifer Franke, MDh,
- Annahita Sarcon, MDi,
- L. Christian Napp, MDj,
- Milosz Jaguszewski, MD, PhDk,
- Michel Noutsias, MDl,
- Hugo A. Katus, MDh,
- Christof Burgdorf, MDm,
- Heribert Schunkert, MDn,o,
- Holger Thiele, MDp,
- Johann Bauersachs, MDj,
- Carsten Tschöpe, MDq,
- Burkert M. Pieske, MD, PhDq,
- Lawrence Rajan, MDr,
- Guido Michels, MDs,
- Roman Pfister, MDs,
- Alessandro Cuneo, MDt,
- Claudius Jacobshagen, MDu,
- Gerd Hasenfuß, MDu,
- Mahir Karakas, MDv,w,
- Wolfgang Koenig, MDn,o,
- Wolfgang Rottbauer, MDx,
- Samir M. Said, MDy,
- Ruediger C. Braun-Dullaeus, MDy,
- Adrian Banning, MDz,
- Florim Cuculi, MDaa,
- Richard Kobza, MDaa,
- Thomas A. Fischer, MDbb,
- Tuija Vasankari, MDcc,
- K.E. Juhani Airaksinen, MDcc,
- Grzegorz Opolski, MDdd,
- Rafal Dworakowski, MDee,
- Philip MacCarthy, MD, PhDee,
- Christoph Kaiser, MDff,
- Stefan Osswald, MDff,
- Leonarda Galiuto, MD, PhDgg,
- Filippo Crea, MDgg,
- Wolfgang Dichtl, MD, PhDhh,
- Klaus Empen, MDii,jj,
- Stephan B. Felix, MDii,jj,
- Clément Delmas, MDkk,
- Olivier Lairez, MD, PhDkk,
- Ibrahim El-Battrawy, MDll,mm,
- Ibrahim Akin, MDll,mm,
- Martin Borggrefe, MDll,mm,
- John Horowitz, MBBS, PhDnn,
- Martin Kozel, MDoo,
- Petr Tousek, MD, PhDoo,
- Petr Widimský, MD, PhDoo,
- Ekaterina Gilyarova, MDpp,
- Alexandra Shilova, MD, PhDpp,
- Mikhail Gilyarov, MD, PhDpp,
- David E. Winchester, MDqq,
- Christian Ukena, MDrr,
- Jeroen J. Bax, MD, PhDss,
- Abhiram Prasad, MDtt,
- Michael Böhm, MDrr,
- Thomas F. Lüscher, MDuu,vv,
- Frank Ruschitzka, MDa and
- Christian Templin, MD, PhDa,∗ ()
- aUniversity Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
- bDivision of Cardiology, Department of Medical Sciences, AOU Citta della Salute e della Scienza, University of Turin, Turin, Italy
- cDivision of Biological Sciences, University of California, San Diego, La Jolla, California
- dDepartment of Mathematics and Computer Science, University of Bremen, Bremen, Germany
- eDepartment of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
- fHeart Department, University Hospital “San Giovanni di Dio e Ruggi d'Aragona”, Salerno, Italy
- gCardiology 1, Center for Cardiology, University Medical Center Mainz, Mainz, Germany
- hDepartment of Cardiology, Heidelberg University Hospital, Heidelberg, Germany
- iUniversity of Southern California, Keck School of Medicine, Los Angeles, California
- jDepartment of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
- kFirst Department of Cardiology, Medical University of Gdansk, Gdansk, Poland
- lDepartment of Internal Medicine III, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle, Martin-Luther-University Halle, Halle (Saale), Germany
- mHeart and Vascular Centre Bad Bevensen, Bad Bevensen, Germany
- nDeutsches Herzzentrum München, Technische Universität München, Munich, Germany
- oDZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
- pHeart Center Leipzig, University Hospital, Department of Internal Medicine/Cardiology, Leipzig, Germany
- qDepartment of Cardiology, Charité, Campus Rudolf Virchow, Berlin, Germany
- rTJ Health Partners Heart and Vascular, Glasgow, Kentucky
- sDepartment of Internal Medicine III, Heart Center University of Cologne, Cologne, Germany
- tKrankenhaus “Maria Hilf” Medizinische Klinik, Stadtlohne, Germany
- uClinic for Cardiology and Pneumology, Georg August University Goettingen, Goettingen, Germany
- vDepartment of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany
- wDZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, Hamburg, Germany
- xDepartment of Internal Medicine II–Cardiology, University of Ulm, Medical Center, Ulm, Germany
- yInternal Medicine/Cardiology, Angiology, and Pneumology, Magdeburg University, Magdeburg, Germany
- zDepartment of Cardiology, John Radcliffe Hospital, Oxford University Hospitals, Oxford, United Kingdom
- aaDepartment of Cardiology, Kantonsspital Lucerne, Lucerne, Switzerland
- bbDepartment of Cardiology, Kantonsspital Winterthur, Winterthur, Switzerland
- ccHeart Center, Turku University Hospital and University of Turku, Turku, Finland
- ddDepartment of Cardiology, Medical University of Warsaw, Warsaw, Poland
- eeDepartment of Cardiology, Kings College Hospital, Kings Health Partners, London, United Kingdom
- ffDepartment of Cardiology, University Hospital Basel, Basel, Switzerland
- ggDepartment of Cardiovascular Sciences, Catholic University of the Sacred Heart Rome, Rome, Italy
- hhUniversity Hospital for Internal Medicine III (Cardiology and Angiology), Medical University Innsbruck, Innsbruck, Austria
- iiUniversity Medicine Greifswald, Department of Internal Medicine B, Greifswald, Germany
- jjDZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
- kkDepartment of Cardiology and Cardiac Imaging Center, University Hospital of Rangueil, Toulouse, France
- llFirst Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM) University of Heidelberg, Mannheim, Germany
- mmDZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg-Mannheim, Mannheim, Germany
- nnDepartment of Cardiology, Basil Hetzel Institute, Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia
- ooCharles University in Prague and University Hospital Kralovske Vinohrady, Prague, Czech Republic
- ppIntensive Coronary Care Unit, Moscow City Hospital #1 named after N. Pirogov, Moscow, Russia
- qqDepartment of Medicine, College of Medicine, University of Florida, Gainesville, Florida
- rrKlinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
- ssDepartment of Cardiology, Leiden University Medical Centre, Leiden, the Netherlands
- ttDivision of Cardiovascular Diseases Mayo Clinic, Rochester, Minnesota
- uuCenter for Molecular Cardiology, Schlieren Campus, University of Zurich, Switzerland
- vvRoyal Brompton and Harefield Hospitals Trust and Imperial College, London, United Kingdom
- ↵∗Address for correspondence:
Dr. Christian Templin, Andreas Grüntzig Heart Catheterization Laboratories, University Hospital Zurich, University Heart Center – Department of Cardiology, Raemistrasse 100, 8091 Zurich, Switzerland.
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)
Takotsubo syndrome (TTS) has been considered a relatively benign condition since its initial description in 1990 (1). Recently, we have revealed TTS as a life-threatening condition with comparable in-hospital adverse outcomes to acute coronary syndrome (ACS) (2). However, scarce data exist on long-term outcomes in patients with TTS compared with patients with ACS.
TTS can be associated with a preceding emotional or physical stressor, and approximately two-thirds of patients have identifiable triggering events (2,3). Recent data have indicated that in-hospital outcomes in TTS patients with a preceding medical illness are worse than that of patients with an emotional stressor or without an identified stressor (4–6). However, the effect of triggering events on short- and long-term outcome has not been fully investigated. This is of particular interest, as triggering factors may significantly affect the prognosis of TTS. Physical stressors include a wide spectrum of conditions, such as neurologic conditions, pheochromocytoma, and other physical activities, medical conditions, or procedures (7,8), validating the hypothesis that patients with different physical triggers have different outcomes.
The aim of the present study was to compare the prognosis between TTS and ACS patients and to investigate short- and long-term outcomes in TTS according to different triggers using the database from InterTAK (International Takotsubo) Registry cohort (2,9).
Patients and inclusion criteria
TTS patients were included from the InterTAK Registry as previously described (2,10). Data were queried from the University Hospital Zurich and 25 collaborating hospitals in 9 countries (Austria, Finland, France, Germany, Italy, Poland, Switzerland, United Kingdom, and the United States) from January 1, 2011, to December 31, 2014. TTS was defined based on modified Mayo Clinic Diagnostic Criteria (2,11): 1) a transient wall motion abnormality in the left ventricle beyond a single epicardial coronary artery distribution; 2) the absence of obstructive coronary artery disease or angiographic evidence of acute plaque rupture, which can explain the wall motion abnormality; 3) new electrocardiographic abnormalities or elevation in cardiac troponin values; and 4) the absence of myocarditis. Patients with focal TTS matching all other criteria, in whom the wall-motion abnormality was identical to a single coronary artery territory coincidentally, were included. TTS patients who died during the acute phase before complete recovery of wall motion were not excluded. When eligibility for inclusion was unclear, cases were reviewed by core members at the University Hospital Zurich to reach an agreement. As a control group, an age- and sex-matched cohort of patients with ACS, including patients with ST-segment elevation myocardial infarction, non–ST-segment elevation myocardial infarction, or unstable angina, was selected from the Zurich Acute Coronary Syndrome Registry. The detailed methods of ACS patient selection have already been described in our previous paper (2). Data on clinical profile and outcome were collected. This included demographics, vital signs, cardiovascular risk factors, comorbidities, laboratory values, results on electrocardiography and coronary angiography, use of medications, and use of critical care. Follow-up information of both TTS and ACS patients was obtained through telephone interviews, clinical visits, or medical records.
Patients were categorized into respective groups according to the types of preceding stressors—emotional stress, physical stress, and no identifiable trigger. In addition, physical stressors were categorized into 2 groups: 1) physical activities, medical conditions, or procedures; and 2) neurologic disorders. Patients with the combination of emotional and physical stress were excluded from the present analysis.
Long-term mortality of patients with TTS was compared with an age- and sex-matched cohort of patients with ACS. Additionally, short- and long-term outcomes including death from any cause were compared between the TTS groups based on triggers and with ACS patients.
Continuous data are shown as mean ± SD, skewed variables are presented as median (interquartile range), and categorical variables are given as numbers and percentages. Comparisons of patients’ characteristics between different groups were performed with 1-way analysis of variance or the Kruskal-Wallis test for continuous data and the Pearson chi-square test for categorical variables.
Outcome analysis was performed using Kaplan-Meier estimates and log-rank tests, as well as a landmark analysis with a landmark set at 30 days. Cox regression analysis was conducted to determine the hazard ratio (HR) and 95% confidence intervals (CIs) for long-term outcome of respective trigger factors using patients with an emotional stressor as a reference. To account for possible differences in clinical characteristics and comorbidities between different TTS groups, a multivariable adjustment analysis, including covariates that had a significant difference in the baseline comparison or were likely to have a relationship to long-term mortality, was performed in a Cox regression model. Missing data on covariates were completed with multiple imputations prior to multivariable Cox regression. An additional Cox regression analysis to obtain predictors of 30-day mortality was also performed. All tests were 2-sided, and statistical significance was defined as p < 0.05. Statistical analyses were performed using IBM SPSS Statistics, version 25.0 (IBM, Armonk, New York). Graphs were compiled with Prism 7 (GraphPad, La Jolla, California).
Comparison of TTS patients to age- and sex-matched ACS patients
Of all TTS patients in the InterTAK Registry, 455 patients were included in an analysis for the comparison to an age- and sex-matched cohort of 455 ACS patients, including 233 with ST-segment elevation ACS and 222 with non–ST-segment elevation ACS (2). Patients’ characteristics and in-hospital outcomes of the TTS and age- and sex-matched cohort of ACS have already been published elsewhere (2). Long-term mortality analysis revealed similar outcomes between TTS and ACS patients (p = 0.49) (Figure 1).
Comparison between different trigger groups
To investigate the effects of preceding stress factors, 1,613 patients were included after the exclusion of patients whose triggering conditions could not be clearly differentiated (overlapping of emotional and physical triggers, n = 137), and categorized into respective groups based on triggers. A definite emotional stressor was detected in 485 patients (30%). Of 630 patients (39%) with a physical trigger, 98 patients (6%) were identified as having an acute neurologic disorder. The remaining patients with a physical trigger (n = 532, 33%) experienced TTS secondary to physical activities, medical conditions, or procedures. A total of 31% of TTS patients had no identifiable triggering factor (n = 498).
Main patient characteristics of all different groups are summarized in Table 1. The prevalence of women was significantly higher in TTS related to emotional stress (95%) versus physical activities, medical conditions, or procedures (85%), TTS secondary to neurologic disorders (87%), and TTS without an identifiable triggering factor (91%) (p < 0.001). Patients with TTS secondary to neurologic diseases were significantly younger (age 61.8 ± 14.9 years) compared with the other groups (p < 0.001). Laboratory analysis on admission demonstrated that troponin, creatine kinase, and brain natriuretic peptide were comparable amongst all groups. Inflammatory markers, including C-reactive protein and white blood cell count, were significantly higher in TTS secondary to physical activities, medical conditions, or procedures and TTS secondary to neurologic diseases. There was no difference in electrocardiographic findings on admission. Patients with TTS secondary to physical activities, medical conditions, or procedures and TTS secondary to neurologic diseases had higher heart rates and lower left ventricular ejection fraction on admission (p < 0.001 in both comparisons). Diabetes mellitus was more common in TTS secondary to physical activities, medical conditions, or procedures, while less common in TTS secondary to neurologic diseases. Cancer was more common in TTS secondary to physical activities, medical conditions, or procedures and TTS secondary to neurologic diseases. There were no significant differences in medications on admission, including angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, statins, and aspirin. Acute cardiac care treatment was much more common in TTS secondary to physical activities, medical conditions, or procedures (38%) and TTS secondary to neurologic diseases (50%) compared with the other groups (p < 0.001) (Table 1).
Short- and long-term mortality
Comparison of 30-day mortality between the different groups based on the triggering conditions demonstrated a substantial difference (p < 0.001) (Figure 2). Patients with TTS secondary to neurologic diseases had the worst prognosis, while patients with TTS related to emotional stress showed the most favorable outcome. In addition, a landmark analysis (time point set at 30 days) demonstrated a substantial difference in long-term mortality between the different groups (p < 0.001) (Figure 2). Whereas patients with TTS secondary to neurologic diseases and TTS secondary to physical activities, medical conditions, or procedures had a less favorable long-term outcome than ACS, patients with TTS related to emotional stress had more favorable prognosis compared with ACS. Preceding physical activities, medical conditions, or procedures (HR: 3.78; 95% CI: 2.21 to 6.44; p < 0.001), neurologic disorders (HR: 5.76; 95% CI: 2.96 to 11.2; p < 0.001), and no identifiable trigger (HR: 2.14; 95% CI: 1.20 to 3.82; p = 0.010) emerged as strong independent risk factors for 5-year mortality when using preceding emotional stressors as the reference group (Figure 3). In an additional Cox regression analysis, preceding physical activities, medical conditions, or procedures; neurologic disorders; and no identifiable trigger were also identified as independent predictors of 30-day mortality (Online Figure 1).
The principal findings of the present study were as follows: 1) overall, TTS patients had a similar long-term outcome compared with age- and sex-matched ACS patients; 2) TTS patients with events related to emotional stress had a favorable short- and long-term prognosis; 3) TTS secondary to neurologic diseases had the worst short-term prognosis; and 4) TTS secondary to neurologic diseases and TTS secondary to physical activities, medical conditions, or procedures had significantly higher mortality rates compared with ACS during long-term follow-up.
Recently, we have reported that in-hospital mortality of TTS is similar to that of ACS (2). However, scarce data exist on long-term outcomes in patients with TTS compared with patients with myocardial infarction (12–14). Additionally, these studies (13,15) are limited by the fact that they only include patients with ST-segment elevation myocardial infarction or non–ST-segment elevation myocardial infarction as a comparison group without considering patients with unstable angina, which is important as TTS patients can also present with signs and symptoms of unstable angina and without any notable electrocardiographic abnormalities. Second, these studies have had inconsistent results regarding patient outcomes, with some showing equal mortality rate to ACS, and some showing increased mortality in patients with TTS (12,13,15).
TTS is typically triggered by a preceding emotional or physical stressor, and approximately two-thirds of patients have identifiable triggering events (2,3,16,17). We have recently shown that physical triggers are an independent predictor of a worse in-hospital outcome (2). However, triggering conditions, especially physical triggers of TTS, vary substantially, ranging from critical conditions such as a septic shock treated in the intensive care unit to harmless conditions including vigorous housework (7,18). Therefore, we hypothesized that patients with different physical triggers have different short- and long-term outcomes.
Of note, TTS patients with an emotional stressor more often had typical features of TTS, such as female sex and chest pain, compared with patients in other groups. Interestingly, patients with TTS secondary to a neurologic disorder were significantly younger than TTS patients of other groups. These epidemiological differences might reflect the biological background. Patients with TTS secondary to physical activities, medical conditions, or procedures and those with TTS secondary to neurologic disorders showed higher heart rates compared with those with emotional triggers. This observation might suggest that the degree of catecholamine surge was more severe in patients with physical or neurologic triggers than in those with emotional triggers. Furthermore, it is likely that higher catecholamine levels can increase the risk of developing cardiogenic shock via pump failure due to large ballooning area and/or left ventricular outflow tract obstruction due to hypercontractility of the basal segment (19). In addition, inflammatory markers such as C-reactive protein and white blood cell count were also higher in patients with physical or neurologic disorders. Thus, it is conceivable that a synergistic effect of a severe cardiac dysfunction and enhanced inflammatory response leads to a poor hemodynamic status, which in turn causes an unfavorable short-term outcome.
According to the triggering conditions, TTS patients with events secondary to neurologic disorders had the highest mortality; this is also in line with a recently published work showing that neurologic diseases are associated with an unfavorable outcome (10). This is not surprising, as the prognosis of these patients is likely to be affected by the underlying disease. In other words, the increased mortality in patients with neurologic triggers may be engendered by the combined risk of TTS plus the intrinsic risk of any precipitating comorbidity, such as cerebrovascular hemorrhage. Patients with TTS secondary to physical activities, medical conditions, or procedures had the second worst prognosis at 30-day follow-up. However, TTS secondary to neurologic disorders and TTS secondary to physical activities, medical conditions, or procedures showed almost similar unfavorable outcomes at 5 years after the TTS index event; indeed, neurologic diseases mostly drive patient outcome during the acute phase. As the mortality rate of TTS secondary to physical activities, medical conditions, or procedures increases to that of TTS secondary to neurologic disease at 5-year follow-up, this may be explained by a higher prevalence of chronic coexisting morbidities such as diabetes mellitus in patients with TTS secondary to physical activities, medical conditions, or procedures compared with those with TTS secondary to neurologic diseases. Singh et al. (20) conducted a meta-analysis, which reported that TTS patients with underlying noncardiac conditions showed higher in-hospital mortality rate compared with those without. Of note, our study demonstrates different short- and long-term outcomes of TTS patients with diverse physical triggers. Additionally, TTS patients with an emotional stressor showed a favorable short- and long-term outcome compared with those with a physical stressor or ACS patients. Therefore, TTS is a much more complex syndrome than previously thought, and should be classified according to the underlying trigger event to accurately risk stratify and predict short- and long-term outcomes for individual patients. Thus, we propose a new classification according to results of the present study (Central Illustration). This new classification (InterTAK Classification) could be useful to predict short- and long-term outcomes of TTS patients.
This is a registry of an observational nature. Therefore, invisible confounders cannot be excluded. Patients with physical activity were classified as Class IIa and not as a single category due to the small sample size.
It was assumed for quite a long time that TTS is a benign condition; however, it has recently been shown that TTS is a life-threatening illness with substantial morbidity and mortality in the acute phase and outcomes similar to that of ACS. Given the heterogenous character of triggers, TTS encompasses a wide spectrum ranging from a benign to fatal condition. As such, TTS is much more multifaceted than suggested. The old woman with an emotional triggering event and apical ballooning, “the classic TTS patient,” indeed has a good short- and long-term prognosis, whereas patients with TTS secondary to neurologic disorders and TTS secondary to physical activities, medical conditions, or procedures reveal an unfavorable outcome. As medicine approaches delivery of personalized medicine and our knowledge about TTS grows, it is crucial to consider the “individual patient” to perhaps improve prognosis. Thus, the new InterTAK Classification based on the type of triggering event might be a useful clinical tool for risk stratification.
COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: The long-term outcome of patients with TTS is highly variable. The prognosis is more favorable when the syndrome is triggered by emotional events than when it develops in response to physical or neurologic conditions.
TRANSLATIONAL OUTLOOK: Further investigation of the relationships between the triggering provocative circumstances could help elucidate the pathophysiological mechanisms responsible for this acute cardiac condition.
↵∗ Drs. Ghadri and Kato contributed equally to this work.
Dr. Ghadri has received a research grant “Filling the gap” from the University of Zurich. Dr. Napp has received lecture honoraria from Abiomed, Cytosorbents, KelCon, Maquet, and Zoll; has received consultant fees from Abiomed, Bayer, and Cytosorbents; and has received traveling or congress support from Abbott, Abiomed, Bayer, Biotronik, Boston Scientific, Lilly, Medtronic, Merit Medical, Pfizer, Servier, and Volcano. Dr. Noutsias has received honoraria for presentations and/or participated in advisory boards from Abiomed, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Fresenius, Miltenyi Biotech, Novartis, Pfizer, and Zoll. Dr. Hasenfuß has served as a consultant for Corvia, Servier, Impulse Dynamics, Novartis, and Vifor Pharma; has received lecture fees from Corvia, Servier, Novartis, AstraZeneca, and Vifor Pharma; has served as co-PI for Impulse Dynamics; and has served on the Editorial Board of Springer. Dr. Koenig has received modest consultation fees for advisory board meetings from Novartis, Pfizer, DalCor, Sanofi, Kowa, and Amgen; and has received modest personal fees for lectures from Novartis, Pfizer, Sanofi, AstraZeneca, and Amgen. Dr. Bax’s institution, The Department of Cardiology at Leiden University Medical Center, has received unrestricted research grants from Biotronik, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr. Ruschitzka has attended Advisory Board meetings for AstraZeneca, Sanofi, Amgen, Bristol-Myers Squibb, Pfizer, and Roche; has attended Steering Committee meetings for Fresenius and Vifor; has received lecture fees from St. Jude Medical, Servier, Zoll, Novartis, Bayer, and Abbott; and has received research grants from St. Jude Medical and Novartis. Dr. Templin has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Tani Research Programme. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- acute coronary syndrome
- confidence interval
- hazard ratio
- Takotsubo syndrome
- Received March 28, 2018.
- Revision received June 5, 2018.
- Accepted June 5, 2018.
- 2018 American College of Cardiology Foundation
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