Cardiogenic shock complicates takotsubo syndrome (TTS) in approximately 10

Journal Article Cardiac biomarkers for diagnosing Takotsubo syndrome Get access Victor Schweiger, Victor Schweiger Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Davide Di Vece, Davide Di Vece First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, ItalyInternal Medicine B, University Medicine Greifswald, Greifswald, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Victoria L Cammann, Victoria L Cammann Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Iva Koleva, Iva Koleva Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Würdinger, Michael Würdinger Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas Gilhofer, Thomas Gilhofer Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Katja Rajman, Katja Rajman Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Konrad A Szawan, Konrad A Szawan Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar David Niederseer, David Niederseer Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland https://orcid.org/0000-0003-3089-1222 Search for other works by this author on: Oxford Academic PubMed Google Scholar Rodolfo Citro, Rodolfo Citro Heart Department, University Hospital 'San Giovanni di Dio e Ruggi d'Aragona', Salerno, ItalyDepartment of Vascular Physiopathology, IRCCS Neuromed, Pozzilli, Italy https://orcid.org/0000-0002-7796-6298 Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more Carmine Vecchione, Carmine Vecchione Department of Vascular Physiopathology, IRCCS Neuromed, Pozzilli, ItalyDepartment of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Salerno, Italy https://orcid.org/0000-0002-2473-4565 Search for other works by this author on: Oxford Academic PubMed Google Scholar Eduardo Bossone, Eduardo Bossone Division of Cardiology, 'Antonio Cardarelli' Hospital, Naples, Italy https://orcid.org/0000-0003-2769-9950 Search for other works by this author on: Oxford Academic PubMed Google Scholar Sebastiano Gili, Sebastiano Gili Centro Cardiologico Monzino, IRCCS, Milan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Neuhaus, Michael Neuhaus Department of Cardiology, Kantonsspital Frauenfeld, Frauenfeld, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Jennifer Franke, Jennifer Franke Department of Cardiology, Heidelberg University Hospital, Heidelberg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Benjamin Meder, Benjamin Meder Department of Cardiology, Heidelberg University Hospital, Heidelberg, Germany https://orcid.org/0000-0003-0741-2633 Search for other works by this author on: Oxford Academic PubMed Google Scholar Miłosz Jaguszewski, Miłosz Jaguszewski First Department of Cardiology, Medical University of Gdansk, Gdansk, Poland Search for other works by this author on: Oxford Academic PubMed Google Scholar Michel Noutsias, Michel Noutsias Mid-German Heart Center, Department of Internal Medicine III, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Maike Knorr, Maike Knorr Center for Cardiology, Cardiology 1, University Medical Center Mainz, Mainz, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas Jansen, Thomas Jansen Center for Cardiology, Cardiology 1, University Medical Center Mainz, Mainz, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Fabrizio D'Ascenzo, Fabrizio D'Ascenzo Division of Cardiology, Department of Medical Sciences, AOU Città della Salute e della Scienza, University of Turin, Turin, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Francesco Bruno, Francesco Bruno Division of Cardiology, Department of Medical Sciences, AOU Città della Salute e della Scienza, University of Turin, Turin, ItalyRoyal Brompton and Harefield Hospitals Trust and Imperial College, London, UK https://orcid.org/0000-0003-0019-0273 Search for other works by this author on: Oxford Academic PubMed Google Scholar Ovidio De Filippo, Ovidio De Filippo Royal Brompton and Harefield Hospitals Trust and Imperial College, London, UK https://orcid.org/0000-0002-4915-9501 Search for other works by this author on: Oxford Academic PubMed Google Scholar Giulio Stefanini, Giulio Stefanini Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, ItalyHumanitas Research Hospital IRCCS, Rozzano, Milan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Gianluca Campo, Gianluca Campo Azienda Ospedaliero-Universitaria di Ferrara, University of Ferrara, Italy https://orcid.org/0000-0002-5150-188X Search for other works by this author on: Oxford Academic PubMed Google Scholar Wojciech Wanha, Wojciech Wanha Medical University of Silesia, Katowice, Poland Search for other works by this author on: Oxford Academic PubMed Google Scholar Sergio Raposeiras Roubin, Sergio Raposeiras Roubin Hospital Álvaro Cunqueiro, Vigo, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar Wolfgang Dichtl, Wolfgang Dichtl University Hospital for Internal Medicine III (Cardiology and Angiology), Medical University Innsbruck, Innsbruck, Austria Search for other works by this author on: Oxford Academic PubMed Google Scholar Dirk von Lewinski, Dirk von Lewinski Division of Cardiology, Medical University of Graz, Graz, Austria https://orcid.org/0000-0001-9996-6128 Search for other works by this author on: Oxford Academic PubMed Google Scholar Christof Burgdorf, Christof Burgdorf Heart and Vascular Centre Bad Bevensen, Bad Bevensen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Behrouz Kherad, Behrouz Kherad Department of Cardiology, Charité, Campus Rudolf Virchow, Berlin, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Carsten Tschöpe, Carsten Tschöpe Department of Cardiology, Charité, Campus Rudolf Virchow, Berlin, Germany https://orcid.org/0000-0001-5243-8985 Search for other works by this author on: Oxford Academic PubMed Google Scholar Annahita Sarcon, Annahita Sarcon Section of Cardiac Electrophysiology, Department of Medicine, University of California-San Francisco, San Francisco, CA, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Jerold Shinbane, Jerold Shinbane University of Southern California, Keck School of Medicine, Los Angeles, CA, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Lawrence Rajan, Lawrence Rajan TJ Health Partners Heart and Vascular, Glasgow, KY, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Guido Michels, Guido Michels Klinik für Akut- und Notfallmedizin, St.-Antonius-Hospital gGmbH, Akademisches Lehrkrankenhaus der RWTH Aachen, Eschweiler, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Roman Pfister, Roman Pfister Department of Internal Medicine III, Heart Center University of Cologne, Cologne, Germany https://orcid.org/0000-0002-4358-5008 Search for other works by this author on: Oxford 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Google Scholar P Christian Schulze, P Christian Schulze Department of Internal Medicine I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Matteo Bianco, Matteo Bianco Division of Cardiology, A.O.U San Luigi Gonzaga, Orbassano, Turin, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Lucas Jörg, Lucas Jörg Department of Cardiology, Kantonsspital St. Gallen, St. Gallen, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Hans Rickli, Hans Rickli Department of Cardiology, Kantonsspital St. Gallen, St. Gallen, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Gonçalo Pestana, Gonçalo Pestana Department of Cardiology, Centro Hospitalar Universitário de São João, E.P.E., Porto, Portugal Search for other works by this author on: Oxford Academic PubMed Google Scholar Thanh H Nguyen, Thanh H Nguyen Department of Cardiology, Basil Hetzel Institute, Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Böhm, Michael Böhm Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany https://orcid.org/0000-0002-2976-2514 Search for other works by this author on: Oxford Academic PubMed Google Scholar Lars S Maier, Lars S Maier Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Fausto J Pinto, Fausto J Pinto Santa Maria University Hospital, CHULN, Center of Cardiology of the University of Lisbon, Lisbon School of Medicine, Lisbon Academic Medical Center, Lisboa, Portugal Search for other works by this author on: Oxford Academic PubMed Google Scholar Petr Widimský, Petr Widimský Cardiocenter, Third 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https://orcid.org/0000-0001-7368-0500 Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas F Lüscher, Thomas F Lüscher Royal Brompton and Harefield Hospitals Trust and Imperial College, London, UKCenter for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Filippo Crea, Filippo Crea Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Frank Ruschitzka, Frank Ruschitzka Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Jelena R Ghadri, Jelena R Ghadri Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Christian Templin Christian Templin Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zurich, SwitzerlandSwiss CardioVascularClinic, Private Hospital Bethanien, Zurich, Switzerland Corresponding author. Tel: +044 255 11 11, Email: christian.templin@usz.ch https://orcid.org/0000-0003-0287-4193 Search for other works by this author on: Oxford Academic PubMed Google Scholar European Heart Journal, ehae231, https://doi.org/10.1093/eurheartj/ehae231 Published: 08 May 2024 Article history Received: 22 August 2023 Revision received: 08 March 2024 Accepted: 25 March 2024 Published: 08 May 2024

The perception of takotsubo syndrome (TTS) has evolved significantly over the years, primarily driven by increased recognition of acute complications and mortality. This study aimed to explore temporal trends in demographic patterns, risk factors, clinical presentations, and outcomes in patients with TTS. Patients diagnosed with TTS between 2004 and 2021 were enrolled from the InterTAK (International Takotsubo) registry. To assess temporal trends, patients were divided into 6 groups, each corresponding to a 3-year interval within the study period. Overall, 3,957 patients were included in the study. There was a significant demographic transition, with the proportion of male patients rising from 10% to 15% (P = 0.003). Although apical TTS remained the most common form, the diagnosis of midventricular TTS increased from 18% to 28% (P = 0.018). The prevalence of physical triggers increased from 39% to 58% over the years (P < 0.001). There was a significant increase in 60-day mortality over the years (P < 0.001). However, a landmark analysis excluding patients who died within the first 60 days showed no differences in 1-year mortality (P = 0.150). This study of temporal trends in TTS highlights a transition in patients demographic with a growing prevalence among men, increasing recognition of midventricular TTS type, and increased short-term mortality and rates of cardiogenic shock in recent years. This transition aligns with the rising prevalence of physical triggers, as expression of increased recognition of TTS in association with acute comorbidities.

BACKGROUND:The perception of takotsubo syndrome (TTS) has evolved significantly over the years, primarily driven by increased recognition of acute complications and mortality. OBJECTIVES:This study aimed to explore temporal trends in demographic patterns, risk factors, clinical presentations, and outcomes in patients with TTS. METHODS:Patients diagnosed with TTS between 2004 and 2021 were enrolled from the InterTAK (International Takotsubo) registry. To assess temporal trends, patients were divided into 6 groups, each corresponding to a 3-year interval within the study period. RESULTS:Overall, 3,957 patients were included in the study. There was a significant demographic transition, with the proportion of male patients rising from 10% to 15% (P = 0.003). Although apical TTS remained the most common form, the diagnosis of midventricular TTS increased from 18% to 28% (P = 0.018). The prevalence of physical triggers increased from 39% to 58% over the years (P < 0.001). There was a significant increase in 60-day mortality over the years (P < 0.001). However, a landmark analysis excluding patients who died within the first 60 days showed no differences in 1-year mortality (P = 0.150). CONCLUSIONS:This study of temporal trends in TTS highlights a transition in patients demographic with a growing prevalence among men, increasing recognition of midventricular TTS type, and increased short-term mortality and rates of cardiogenic shock in recent years. This transition aligns with the rising prevalence of physical triggers, as expression of increased recognition of TTS in association with acute comorbidities.

AIMS:Takotsubo syndrome (TTS) is associated with a substantial rate of adverse events. We sought to design a machine learning (ML)-based model to predict the risk of in-hospital death and to perform a clustering of TTS patients to identify different risk profiles. METHODS AND RESULTS:A ridge logistic regression-based ML model for predicting in-hospital death was developed on 3482 TTS patients from the International Takotsubo (InterTAK) Registry, randomly split in a train and an internal validation cohort (75% and 25% of the sample size, respectively) and evaluated in an external validation cohort (1037 patients). Thirty-one clinically relevant variables were included in the prediction model. Model performance represented the primary endpoint and was assessed according to area under the curve (AUC), sensitivity and specificity. As secondary endpoint, a K-medoids clustering algorithm was designed to stratify patients into phenotypic groups based on the 10 most relevant features emerging from the main model. The overall incidence of in-hospital death was 5.2%. The InterTAK-ML model showed an AUC of 0.89 (0.85-0.92), a sensitivity of 0.85 (0.78-0.95) and a specificity of 0.76 (0.74-0.79) in the internal validation cohort and an AUC of 0.82 (0.73-0.91), a sensitivity of 0.74 (0.61-0.87) and a specificity of 0.79 (0.77-0.81) in the external cohort for in-hospital death prediction. By exploiting the 10 variables showing the highest feature importance, TTS patients were clustered into six groups associated with different risks of in-hospital death (28.8% vs. 15.5% vs. 5.4% vs. 1.0.8% vs. 0.5%) which were consistent also in the external cohort. CONCLUSION:A ML-based approach for the identification of TTS patients at risk of adverse short-term prognosis is feasible and effective. The InterTAK-ML model showed unprecedented discriminative capability for the prediction of in-hospital death.

Dilated cardiomyopathy (DCM) is characterized by ventricular chamber enlargement and impaired myocardial function. Endomyocardial biopsies (EMB) enable immunohistochemical and molecular characterization of this disease. However, knowledge about specific molecular patterns and their relation to cardiac function in both ventricles is rare. Therefore, we performed a mass spectrometric analysis of 28 paired EMBs of left (LV) and right ventricles (RV) of patients with DCM or suspected myocarditis allowing quantitative profiling of 743 proteins. We analysed associations between protein abundance of LV and RV as well as the echocardiographic parameters LVEF, TAPSE, LVEDDI, and RVEDDI by linear regression models. Overall, more LV than RV proteins were associated with LV parameters or with RVEDDI. Most LV and RV proteins increasing in level with impairing of LVEF were annotated to structural components of cardiac tissue. Additionally, a high proportion of LV proteins with metabolic functions decreased in level with decreasing LVEF. Results were validated with LV heart sections of a genetic murine heart failure model. The study shows, that remodelling and systolic dysfunction in DCM is mirrored by distinct alterations in protein composition of both ventricles. Loss of LV systolic function is reflected predominantly by alterations in proteins assigned to metabolic functions in the LV whereas structural remodelling was more obvious in the RV. Alterations related to intermediate filaments were seen in both ventricles and highlight such proteins as early indicators of LV loss of function. SIGNIFICANCE: The present study report protein sets in the RV and the LV being associated with ventricular function and remodelling in DCM. Protein abundances in the LV and the RV emphasize and expand current knowledge on pathophysiological changes in heart failure and DCM. While RV and LV EMBs do not differ concerning diagnostic assessment of inflammatory status and virus persistence, additional information reflecting disease severity associated protein alterations can be gained by EMB protein profiling. RV and LV protein data provided complementary information. The protein pattern of the LV reflects metabolic changes and an impaired energy production, which is associated with the degree of LV systolic dysfunction and remodelling and may yield important information about the disease status in DCM. On the other hand, at this disease stage of DCM with still preserved RV function, RV alterations in structural proteins may reflect myocardial compensatory protective mechanisms for maintenance of structure and cellular function. The study highlight particular proteins being of interest as heart failure biomarkers in both ventricles which seem to reflect the severity of the disease. Further comparative studies between different HF aetiologies have to evaluate those proteins as markers specific for DCM.

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.

Was ist neu? Diagnostisches Vorgehen Im Rahmen einer standardisierten Vorgehensweise kann die nichtinvasive kardiale Diagnostik erste Hinweise für das Vorliegen einer Myokarditis liefern, bevor mittels Myokardbiopsie anhand histologischer und immunhistochemischer Kriterien die Sicherung der Diagnose erfolgt. Bei Verdacht auf eine Myokarditis sollte zudem eine Magnetresonanztomografie (MRT) durchgeführt werden, die mit hoher diagnostischer Güte den Nachweis einer Entzündung und eines Ödems als spezifische Myokarditis-Befunde ermöglicht und Aufschluss über die regionale Verteilung und Ausprägung der pathologischen Veränderungen gibt. Geschlechtsspezifische Unterschiede bei der Myokarditis Bei Frauen sollte auch bei nur geringem Hinweis auf eine Myokarditis eine diagnostische Standardroutine erfolgen. Krankheitssymptome sowie die Erhöhung der Kreatinkinase und des Myoglobins sind bei ihnen weniger stark ausgeprägt als bei Männern. Therapie Die Grundlage der Myokarditis-Therapie bildet die leitliniengerechte Behandlung der Symptome, einer eventuell bestehenden Herzinsuffizienz sowie, bei hämodynamischer Instabilität, eine intensivmedizinische Behandlung. Für den Nutzen spezifischer immunmodulatorischer oder immunsuppressiver Therapieansätze gibt es, mit Ausnahme der seltenen Riesenzellmyokarditis, derzeit noch keine gesicherten klinischen Daten.

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 = 0.002) and had an increased prevalence of acute neurological (16.3% vs. 8.4% vs. 8.8%; p = 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 = 0.004) and had a numerically higher in-hospital mortality (6.6% vs. 3.6% vs. 5.1%; p = 0.07). At multivariable analysis, younger (odds ratio: 1.60; 95% confidence interval: 0.86 to 3.01; p = 0.14) and older age (odds ratio: 1.09; 95% confidence interval: 0.66 to 1.80; p = 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.

AIMS:Takotsubo syndrome (TTS) is an acute heart failure syndrome, which shares many features with acute coronary syndrome (ACS). Although TTS was initially described with angiographically normal coronary arteries, smaller studies recently indicated a potential coexistence of coronary artery disease (CAD) in TTS patients. This study aimed to determine the coexistence, features, and prognostic role of CAD in a large cohort of patients with TTS.METHODS AND RESULTS:Coronary anatomy and CAD were studied in patients diagnosed with TTS. Inclusion criteria were compliance with the International Takotsubo Diagnostic Criteria for TTS, and availability of original coronary angiographies with ventriculography performed during the acute phase. Exclusion criteria were missing views, poor quality of angiography loops, and angiography without ventriculography. A total of 1016 TTS patients were studied. Of those, 23.0% had obstructive CAD, 41.2% had non-obstructive CAD, and 35.7% had angiographically normal coronary arteries. A total of 47 patients (4.6%) underwent percutaneous coronary intervention, and 3 patients had acute and 8 had chronic coronary artery occlusion concomitant with TTS, respectively. The presence of CAD was associated with increased incidence of shock, ventilation, and death from any cause. After adjusting for confounders, the presence of obstructive CAD was associated with mortality at 30 days. Takotsubo syndrome patients with obstructive CAD were at comparable risk for shock and death and nearly at twice the risk for ventilation compared to an age- and sex-matched ACS cohort.CONCLUSIONS:Coronary artery disease frequently coexists in TTS patients, presents with the whole spectrum of coronary pathology including acute coronary occlusion, and is associated with adverse outcome.TRIAL REGISTRATION:ClinicalTrials.gov number: NCT01947621.

Myocarditis is a heterogenous disease regarding aetiology, clinical presentation and course. A defined diagnostic procedure is needed to reliably detect myocarditis. While findings from medical laboratory parameters, electrocardiography and echocardiography are rather unspecific, endomyocardial biopsies supply dependable data regarding inflammatory and viral status. Analysis of cardiac MR is constantly being improved in order to increase sensitivity regarding myocarditis detection. Incidence, clinical presentation as well as disease progression and prognosis show considerable gender differences. Adamant implementation of defined diagnostic procedures is needed in order not to overlook myocarditis in women while the understanding of the pathomechanisms behind the gender differences might lead the way to new therapeutic options. Currently, treatment of myocarditis symptoms and heart failure is in the focus of clinical care. In addition, cardiac involvement in systemic inflammatory diseases should be stringently treated via immunosuppression. Avoidance of physical exercise has to be observed in order to reduce cardiac strain and consequently the number of adverse events.

Background Left ventricular (LV) recovery in takotsubo syndrome (TTS) occurs over a wide‐ranging interval, varying from hours to weeks. We sought to investigate the clinical predictors and prognostic impact of recovery time for TTS patients. Methods and Results TTS patients from the International Takotsubo Registry were included in this study. Cut‐off for early LV recovery was determined to be 10 days after the acute event. Multivariable logistic regression was used to assess factors associated with the absence of early recovery. In‐hospital outcomes and 1‐year mortality were compared for patients with versus without early recovery. We analyzed 406 patients with comprehensive and serial imaging data regarding time to recovery. Of these, 191 (47.0%) had early LV recovery and 215 (53.0%) demonstrated late LV improvement. Patients without early recovery were more often male (12.6% versus 5.2%; P=0.011) and presented more frequently with typical TTS (76.3% versus 67.0%, P=0.040). Cardiac and inflammatory markers were higher in patients without early recovery than in those with early recovery. Patients without early recovery showed unfavorable 1‐year outcome compared with patients with early recovery (P=0.003). On multiple logistic regression, male sex, LV ejection fraction <45%, and acute neurologic disorders were associated with the absence of early recovery. Conclusions TTS patients without early LV recovery have different clinical characteristics and less favorable 1‐year outcome compared with patients with early recovery. The factors associated with the absence of early recovery included male sex, reduced LV ejection fraction, and acute neurologic events. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

To identify potential biomarkers supporting better phenotyping and to improve understanding of the pathophysiology of dilated cardiomyopathy (DCM), this study comparatively analyzed plasma protein profiles of DCM patients and individuals with low normal and normal left ventricular ejection fraction (LVEF) by mass spectrometry. After plasma depletion using a MARS Hu-6 column, global proteome profiling was performed using a LTQ-Orbitrap Velos mass spectrometer. To compare and confirm results, two different discovery sets of samples were investigated. Differentially abundant proteins are involved in lipid metabolism, coagulation, and acute phase response. Serum paraoxonase 1 (PON1), cystatin C, lysozyme C, apolipoprotein A-II, and apolipoprotein M were validated by targeted protein analysis in a third independent patient cohort. Additionally, PON1 levels were also determined by an ELISA. These data highlight PON1 as a potential marker for differentiating DCM patients not only from patients with normal LVEF, but also from heart failure patients with preserved ejection fraction. The results highlight lipid metabolism and inflammation as the major pathways being altered in DCM patients in comparison to patients presenting with suspicious myocarditis to the hospital. SIGNIFICANCE: Several studies focused on the identification of heart failure (HF) associated protein signatures in blood plasma, but only few that are largely based on only small sample series considered specific HF pathologies. Therefore, we performed a comparative global blood plasma protein profiling of a larger sample of individuals with reduced left ventricular ejection fraction (LVEF) classified as dilated cardiomyopathy patients and individuals with normal LVEF but presenting with suspicious myocarditis. DCM patients displayed altered levels of proteins involved in lipid metabolism, coagulation, and acute phase response. The most reliable candidates, such as serum paraoxonase 1 (PON1), cystatin C, lysozyme C, apolipoprotein A-II, and apolipoprotein M were validated by targeted protein analysis in an independent patient cohort. PON1 levels were also determined by an ELISA. These data highlight PON1 as a potential marker for differentiating DCM patients not only from patients with normal LVEF, but also from heart failure patients with preserved ejection fraction.

Recent evidence suggests comparable in-hospital and long-term outcomes between takotsubo syndrome (TTS) and acute coronary syndrome.1, 2 Medical scoring systems are practical tools for decision making and prognostic assessment. However, TTS-specific scoring systems for risk stratification have not yet been established. Recently, classification based on triggering conditions proved useful in predicting adverse outcomes in TTS (InterTAK Classification).1 Since clinical parameters other than triggering conditions can be associated with adverse outcomes in TTS, such as systolic blood pressure and heart rate,3 the present study aimed to establish a scoring system combining triggering factors with other important but easily- obtainable clinical parameters of daily clinical practice. Takotsubo syndrome patients were enrolled from the International Takotsubo (InterTAK) Registry, which is an all-comers TTS registry in collaboration with 26 centres worldwide.2 Univariate Cox regression analyses for all-cause mortality were performed with variables of interest based on updated knowledge and recent literature1-6: age (cut-off = 70 years), triggering factors (InterTAK Classification), sex, hypertension, diabetes mellitus, typical or atypical TTS type, heart rate on admission (cut-off = 94 bpm), systolic blood pressure on admission (cut-off = 119 mmHg), left ventricular ejection fraction (cut-off = 45%) and white blood cell count on admission. Patients with missing values for these parameters were excluded. All variables with significance on univariate analysis were entered into a Cox regression model for all-cause mortality with respect to factor interactions. The Cox regression model was internally validated using 1000 bootstrap samples. The bootstrap was used to develop a regression coefficient-based scoring system in the presence of competing risks. The regression (beta) coefficients of the significant risk factors were multiplied by 10 and rounded to the nearest integer to derive item points. These points were then incorporated into the InterTAK Prognostic Score, calculated by the summation of points associated with each risk factor: InterTAK Prognostic Score = γ1 × risk factor A1 + γ2 × risk factor A2 + … + γn × risk factor An, where γ1, γ2,…, γn denote the item points of the risk factor Ai. Optimal cut-off values were determined through decision tree analysis with exhaustive CHAID algorithm. Based on these cut-off values, patients were categorized into four groups: low, intermediate, high, and very high risk. Survival distributions and median survival times of each group were estimated using the Kaplan–Meier (KM) product–limit method and were compared using the log-rank test. Time-dependent receiver operating characteristic curves from censored survival data using KM or nearest neighbor estimation (NNE) method were used to assess score predictive performance in terms of area under the curve (AUC) for various time points. All tests were two-tailed and statistical significance was defined as P < 0.05. Statistical analyses were performed using R (version 3.5; R Foundation for Statistical Computing, Vienna, Austria) and SPSS (version 25; IBM Corp., Armonk, NY, USA). A total of 1160 patients (90.8% females; mean age 66.5 ± 13.0 years) were included in the present study. Overall, 80.6% of patients showed typical TTS type and mean left ventricular ejection fraction was 41.1% ± 11.6%. Mean systolic blood pressure and heart rate on admission were 130.2 ± 27.6 mmHg and 87.9 ± 21.9 bpm. The prevalence of diabetes mellitus was 13.4%. An emotional trigger (InterTAK Classification, Class I) was identified in 32.6% of TTS patients while 32.1% had preceding physical activities, medical conditions, or procedures (Class IIa) and 5.7% had preceding neurologic disorders (Class IIb). The remaining patients (29.7%) had no identifiable triggering factors (Class III). According to bootstrap results, points were assigned to each risk factor that was independently associated with all-cause mortality (Figure 1A). Based on the total points, patients were categorized into four risk groups: low risk ≤ 15 points (37.8%), intermediate risk 16–22 points (23.4%), high risk 23–28 points (28.4%), and very high risk ≥ 29 points (10.4%). The four risk groups showed significant differences in all-cause mortality when using the low-risk group as reference [intermediate risk: hazard ratio (HR) 3.15, 95% confidence interval (CI) 1.74–5.72, P < 0.001; high risk: HR 6.16, 95% CI 3.46–10.98, P < 0.001, and very high risk: HR 11.82, 95% CI 6.56–21.28, P < 0.001] (Figure 1B). The AUCs for KM or NNE showed that the score predictive performance is almost stable from 30 days post-admission (KM/NNE-AUC 0.74/0.74) up to 5 years (KM/NNE-AUC 0.78/0.77). Although well-known scores for other cardiac disorders, such as the CHA2DS2-VASc risk score,7 have been applied as proxy scores for risk evaluation in TTS, there has been no TTS-specific risk score thus far. The present study establishes a novel risk stratification score for TTS (InterTAK Prognostic Score) that only requires variables that are easily obtainable in the acute phase and could identify low to very high risk of all-cause mortality both at short- and long-term. Thus, the InterTAK Prognostic Score could serve as a useful clinical tool to stratify patients according to their risk. C.T. has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme and the Swiss Heart Foundation. L.S.M. was supported by EU HORIZON 2020 (SILICOFCM ID777204). The InterTAK Registry is supported by the Biss Davies Charitable Trust. Conflict of interest: none declared.

To gain new insights into the complex pathophysiology of dilated cardiomyopathy (DCM) we performed a quantitative approach to identify genes with expression patterns that linearly correlate with parameters of cardiac morphology (left ventricular end-diastolic diameter indexed by body surface are (LVEDDI), systolic function [LV ejection fraction (LVEF)], and serum levels of cardiac peptide hormone NH2-terminal probrain natriuretic peptide (NT-proBNP) in human endomyocardial biopsies of 47 DCM patients and eight individuals with normal LVEF. A set of genes was identified as common heart failure markers characterized by correlation of their expression with cardiac morphology, systolic function, and NT-proBNP. Among them are already known genes encoding e.g., the natriuretic peptide hormones NPPA and NPPB and its converting enzyme corin, but also potential new heart failure markers like EP300 antisense RNA1 and dimethylarginine dimethylaminohydrolase 1 (DDAH1) along with other genes with so far unknown relation to heart function. In contrast, the expression of other genes including the Ca2+ flux regulating genes phospholamban (PLN), sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA), and extracellular matrix proteins showed significant correlation with LVEF and LVEDDI only. Those genes seem to reflect more specifically pathological alterations of systolic function and morphology in DCM hearts.

BackgroundMyeloid differentiation factor-2 (MD-2) has been shown to be an important modulator of the innate immune system, but its role in cardiac diseases is unknown. We investigated whether MD-2 plays a role as risk predictor and contributor in dilated cardiomyopathy (DCM).Methods and resultsWe included 174 patients with reduced left ventricular (LV) ejection fraction (LVEF <45%) due to DCM. Coronary artery disease and severe valvular diseases were excluded in all patients by angiography or echocardiography. Cardiac inflammation, viral infection and MD-2 expression were analyzed from right ventricular endomyocardial biopsies. MD-2 was quantified by ELISA in serum upon first hospital admission. Myocyte contractility and inflammatory response after stimulation with recombinant MD-2 protein were analyzed in isolated rat cardiomyocytes.Median follow-up of the patients was 3.51 years (2.73; 4.48) with 34 deaths. Absolute mortality risk increases in patients displaying a MD-2 serum concentration greater than the median (302 ng/ml) was 23% (P < 0.0001). Age- and sex-adjusted Cox regression analyses demonstrated that mortality risk was highly related to MD-2 concentrations (P < 0.001), but not to age or sex. An increase of 100 ng/ml in the MD-2 level was associated with an absolute mortality risk increase of 50.4%. Receiver operating characteristic (ROC) analyses showed no difference between MD-2 and nterminal-pro brain natriuretic peptide (NT-pro-BNP), while the combination of both MD-2 and NT-pro-BNP resulted in a significantly increased capability of risk prediction when compared to NT-pro-BNP alone (P = 0.014). In-vitro, recombinant MD-2 decreases cell shortening and modulates cytokine activation in isolated cardiomyocytes.ConclusionMD-2 predicts long-term outcome in DCM patients and improves mortality risk prediction capability compared to NT-pro-BNP alone. In addition, MD-2 exerts direct negative inotropic effects on isolated cardiomyocytes in-vitro. Further randomized trials should confirm MD-2 as a diagnostic and therapeutic target.

Vasculitides are commonly unrecognized causes of coronary stenosis and myocardial ischemia. We report on a 24-year old patient with Takayasu’s arteritis who underwent urgent percutaneous coronary intervention, suffered from symptomatic restenosis of the left main coronary artery during standard immunosuppressive therapy.

Immunoadsorption with subsequent immunoglobulin substitution (IA/IgG) represents a therapeutic approach for patients with dilated cardiomyopathy (DCM). Here, we studied which molecular cardiac alterations are initiated after this treatment. Transcription profiling of endomyocardial biopsies with Affymetrix whole genome arrays was performed on 33 paired samples of DCM patients collected before and 6 months after IA/IgG. Therapy-related effects on myocardial protein levels were analysed by label-free proteome profiling for a subset of 23 DCM patients. Data were analysed regarding therapy-associated differences in gene expression and protein levels by comparing responders (defined by improvement of left ventricular ejection fraction ≥20 % relative and ≥5 % absolute) and non-responders. Responders to IA/IgG showed a decrease in serum N-terminal proBNP levels in comparison with baseline which was accompanied by a decreased expression of heart failure markers, such as angiotensin converting enzyme 2 or periostin. However, despite clinical improvement even in responders, IA/IgG did not trigger general inversion of DCM-associated molecular alterations in myocardial tissue. Transcriptome profiling revealed reduced gene expression for connective tissue growth factor, fibronectin, and collagen type I in responders. In contrast, in non-responders after IA/IgG, fibrosis-associated genes and proteins showed elevated levels, whereas values were reduced or maintained in responders. Thus, improvement of LV function after IA/IgG seems to be related to a reduced gene expression of heart failure markers and pro-fibrotic molecules as well as reduced fibrosis progression.

Dilated cardiomyopathy (DCM) is a disease of the myocardium with reduced left ventricular ejection fraction (LVEF). Cardiac autoantibodies (AAbs) play a causal role in the development and progression of DCM. Removal of AAbs using immunoadsorption (IA/IgG) has been shown as a therapeutic option to improve cardiac function. However, the response to therapy differs significantly among patients. The reasons for this variability are not completely understood. Hitherto, no potential biomarker is available to predict improvement of cardiac function after therapy accurately. This shotgun proteome study aims to disclose the differences in the endomyocardial proteome between patients with improved LVEF after IA/IgG (responders) and those without improvement (non-responders) before therapy start.Comparative analysis revealed 54 differentially abundant proteins that were mostly confined to carbohydrate and lipid metabolism, energy and immune regulation, and cardioprotection. Selected proteins representing various functional categories were further confirmed by multiple reaction monitoring (MRM). Among those, protein S100-A8, perilipin-4, and kininogen-1 were found the most robust candidates differentiating responders and non-responders. Receiver operating characteristic curve (ROC) analysis of these proteins revealed highest potential for protein S100-A8 (AUC 0.92) with high sensitivity and specificity to be developed as a classifier for the prediction of cardiac improvement after IA/IgG therapy.Significance: We evaluated the differences in the myocardial proteome of responder and non-responder DCM patients before immunoadsorption therapy and identified a number of differentially abundant proteins involved in energy and lipid metabolism, immune system, and cardioprotection. MRM was used for verification of results. Proteins S100-A8, perilipin-4, and kininogen-1 were found to display the largest differences. The results provide a lead for further studies to screen for protein biomarker candidates in plasma that might be helpful to stratify patients for immunoadsorption therapy treatment. (C) 2016 Published by Elsevier B.V.