Intraventricular Thrombus Formation and Embolism in Takotsubo Syndrome

Author:

Ding Katharina J.1,Cammann Victoria L.1,Szawan Konrad A.1,Stähli Barbara E.1,Wischnewsky Manfred2,Di Vece Davide1,Citro Rodolfo3,Jaguszewski Milosz4,Seifert Burkhardt5,Sarcon Annahita6,Knorr Maike7,Heiner Susanne7,Gili Sebastiano8,D’Ascenzo Fabrizio9,Neuhaus Michael10,Napp L. Christian11,Franke Jennifer12,Noutsias Michel13,Burgdorf Christof14,Koenig Wolfgang1516,Kherad Behrouz1718,Rajan Lawrence19,Michels Guido20,Pfister Roman20,Cuneo Alessandro21,Jacobshagen Claudius22,Karakas Mahir2324,Pott Alexander25,Meyer Philippe26,Arroja Jose D.26,Banning Adrian27,Cuculi Florim28,Kobza Richard28,Fischer Thomas A.29,Vasankari Tuija30,Airaksinen K.E. Juhani30,Paolini Carla31,Bilato Claudio31,Carrilho-Ferreira Pedro32,Opolski Grzegorz33,Dworakowski Rafal34,MacCarthy Philip34,Kaiser Christoph35,Osswald Stefan35,Galiuto Leonarda36,Dichtl Wolfgang37,Chan Christina38,Bridgman Paul38,Delmas Clément39,Lairez Olivier39,El-Battrawy Ibrahim4041,Akin Ibrahim4041,Gilyarova Ekaterina42,Shilova Alexandra42,Gilyarov Mikhail42,Kozel Martin43,Tousek Petr43,Widimský Petr43,Winchester David E.44,Galuszka Jan45,Ukena Christian46,Horowitz John D.47,Di Mario Carlo48,Prasad Abhiram49,Rihal Charanjit S.49,Pinto Fausto J.32,Crea Filippo36,Borggrefe Martin4041,Braun-Dullaeus Ruediger C.50,Rottbauer Wolfgang25,Bauersachs Johann11,Katus Hugo A.12,Hasenfuß Gerd22,Tschöpe Carsten1718,Pieske Burkert M.17185152,Thiele Holger53,Schunkert Heribert1516,Böhm Michael46,Felix Stephan B.5455,Münzel Thomas7,Bax Jeroen J.56,Lüscher Thomas F.5758,Ruschitzka Frank1,Ghadri Jelena R.1,Bossone Eduardo59,Templin Christian1

Affiliation:

1. From the Department of Cardiology, University Heart Center, University Hospital Zurich, Switzerland (K.J.D., V.L.C., K.A.S., B.E.S., D.D.V., F.R., J.R.G., C. Templin)

2. Department of Mathematics and Computer Science, University of Bremen, Germany (M.W.)

3. Heart Department, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy (R.C.)

4. First Department of Cardiology, Medical University of Gdansk, Poland (M.J.)

5. Division of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Switzerland (B.S.)

6. Section of Cardiac Electrophysiology, Department of Medicine, University of California-San Francisco (A. Sarcon)

7. Center for Cardiology, Cardiology 1, University Medical Center Mainz, Germany (M. Knorr, S.H., T.M.)

8. Centro Cardiologico Monzino, IRCCS, Milan, Italy (S.G.)

9. Division of Cardiology, Department of Medical Sciences, AOU Città della Salute e della Scienza, University of Turin, Italy (F.D.)

10. Department of Cardiology, Kantonsspital Frauenfeld, Switzerland (M. Neuhaus)

11. Department of Cardiology and Angiology, Hannover Medical School, Germany (L.C.N., J.B.)

12. Department of Cardiology, Heidelberg University Hospital, Germany (J.F., H.A.K.)

13. Department of Internal Medicine III, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle, Martin-Luther-University Halle, Germany (M. Noutsias)

14. Heart and Vascular center Bad Bevensen, Germany (C. Burgdorf)

15. Deutsches Herzzentrum München, Technische Universität München, Munich, Germany (W.K., H.S.)

16. German center for Cardiovascular Research, Partner Site Munich Heart Alliance (W.K., H.S.)

17. Department of Internal Medicine and Cardiology, Charité University Medicine Berlin, Campus Virchow Klinikum, Germany (B.K., C. Tschöpe, B.M.P.)

18. Department of Internal Medicine and Cardiology, German Heart Center Berlin, Germany (B.K., C. Tschöpe, B.M.P.)

19. T.J. Health Partners Heart and Vascular, Glasgow, KY (L.R.)

20. Department of Internal Medicine III, Heart Center University of Cologne, Germany (G.M., R.P.)

21. Krankenhaus “Maria Hilf” Medizinische Klinik, Stadtlohn, Germany (A.C.)

22. Clinic for Cardiology and Pneumology, Georg August University Goettingen, Germany (C.J., G.H.)

23. Department of General and Interventional Cardiology, University Heart Center Hamburg, Germany (M. Karakas)

24. German Centre for Cardiovascular Research, Partner Site Hamburg/Kiel/Luebeck (M. Karakas)

25. Department of Internal Medicine II–Cardiology, University of Ulm, Medical Center, Germany (A. Pott, W.R.)

26. Service de cardiologie, Hôpitaux Universitaires de Genève, Switzerland (P. Meyer, J.D.A.)

27. Department of Cardiology, John Radcliffe Hospital, Oxford University Hospitals, United Kingdom (A.B.)

28. Department of Cardiology, Kantonsspital Lucerne, Switzerland (F. Cuculi, R.K.)

29. Department of Cardiology, Kantonsspital Winterthur, Switzerland (T.A.F.)

30. Heart Center, Turku University Hospital and University of Turku, Finland (T.V., K.E.J.A.)

31. Local Health Unit No. 8, Cardiology Unit, Arzignano, Vicenza, Italy (C.P., C. Bilato)

32. Cardiology Department, Santa Maria University Hospital, Lisbon Academic Medical Centre and Cardiovascular Centre of the University of Lisbon, Lisbon School of Medicine, Universidade de Lisboa, Portugal (P.C.-F., F.J.P.)

33. Department of Cardiology, Medical University of Warsaw, Poland (G.O.)

34. Department of Cardiology, King’s College Hospital, London, United Kingdom (R.D., P. MacCarthy)

35. Department of Cardiology, University Hospital Basel, Switzerland (C.K., S.O.)

36. Department of Cardiovascular Sciences, Catholic University of the Sacred Heart Rome, Italy (L.G., F. Crea)

37. University Hospital for Internal Medicine III (Cardiology and Angiology), Medical University Innsbruck, Austria (W.D.)

38. Department of Cardiology, Christchurch Hospital, New Zealand (C.C., P.B.)

39. Department of Cardiology and Cardiac Imaging Center, University Hospital of Rangueil, Toulouse, France (C.D., O.L.)

40. First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim, University of Heidelberg, Germany (I.E.-B., I.A., M. Borggrefe)

41. German Center for Cardiovascular Research, Partner Site, Heidelberg-Mannheim (I.E.-B., I.A., M. Borggrefe)

42. Intensive Coronary Care Unit, Moscow City Hospital No. 1 named after N. Pirogov, Moscow, Russia (E.G., A. Shilova, M.G.)

43. Cardiocenter, Third Faculty of Medicine, Charles University in Prague and University Hospital Kralovske Vinohrady, Czech Republic (M. Kozel, P.T., P.W.)

44. Division of Cardiovascular Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville (D.E.W.)

45. Department of Internal Medicine I–Cardiology, University Hospital Olomouc, Czech Republic (J.G.)

46. Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany (C.U., M. Böhm)

47. Department of Cardiology, Basil Hetzel Institute, Queen Elizabeth Hospital, University of Adelaide, Australia (J.D.H.)

48. Structural Interventional Cardiology, Careggi University Hospital, Florence, Italy (C.D.M.)

49. Department of Cardiovascular Diseases, Mayo Clinic, Rochester MN (A. Prasad, C.S.R.)

50. Internal Medicine/Cardiology, Angiology, and Pneumology, Magdeburg University, Germany (R.C.B.-D.)

51. German Center for Cardiovascular Research, Partner Site Berlin (B.M.P.)

52. Berlin Institute of Health, Germany (B.M.P.)

53. Department of Internal Medicine/Cardiology, Heart Center Leipzig–University Hospital, Germany (H.T.)

54. Department of Internal Medicine B, University Medicine Greifswald, Germany (S.B.F.)

55. German Centre for Cardiovascular Research, Partner Site Greifswald (S.B.F.)

56. Department of Cardiology, Leiden University Medical Centre, the Netherlands (J.J.B.)

57. Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Switzerland (T.F.L.)

58. Royal Brompton and Harefield Hospitals Trust and Imperial College, London, United Kingdom (T.F.L.)

59. A. Cardarelli Hospital, Naples, Italy (E.B.).

Abstract

Objective: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0–38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×10 3 cells/μL emerged as independent predictors for thrombus formation or embolism. Conclusions: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01947621.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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