Machine learning‐based prediction of in‐hospital death for patients with takotsubo syndrome: The InterTAK‐ML model

Author:

De Filippo Ovidio1,Cammann Victoria L.2,Pancotti Corrado3,Di Vece Davide2,Silverio Angelo4,Schweiger Victor2,Niederseer David2,Szawan Konrad A.2,Würdinger Michael2,Koleva Iva2,Dusi Veronica1,Bellino Michele4,Vecchione Carmine45,Parodi Guido6,Bossone Eduardo7,Gili Sebastiano8,Neuhaus Michael9,Franke Jennifer10,Meder Benjamin10,Jaguszewski Miłosz11,Noutsias Michel12,Knorr Maike13,Jansen Thomas13,Dichtl Wolfgang14,von Lewinski Dirk15,Burgdorf Christof16,Kherad Behrouz17,Tschöpe Carsten17,Sarcon Annahita18,Shinbane Jerold19,Rajan Lawrence20,Michels Guido21,Pfister Roman22,Cuneo Alessandro23,Jacobshagen Claudius2425,Karakas Mahir2627,Koenig Wolfgang2829,Pott Alexander30,Meyer Philippe31,Roffi Marco31,Banning Adrian32,Wolfrum Mathias33,Cuculi Florim33,Kobza Richard33,Fischer Thomas A.34,Vasankari Tuija35,Airaksinen K.E. Juhani35,Napp L. Christian36,Dworakowski Rafal37,MacCarthy Philip37,Kaiser Christoph38,Osswald Stefan38,Galiuto Leonarda39,Chan Christina40,Bridgman Paul40,Beug Daniel4142,Delmas Clément43,Lairez Olivier43,Gilyarova Ekaterina44,Shilova Alexandra44,Gilyarov Mikhail44,El‐Battrawy Ibrahim4546,Akin Ibrahim4546,Poledniková Karolina47,Toušek Petr47,Winchester David E.48,Massoomi Michael48,Galuszka Jan49,Ukena Christian50,Poglajen Gregor51,Carrilho‐Ferreira Pedro52,Hauck Christian53,Paolini Carla54,Bilato Claudio54,Kobayashi Yoshio55,Kato Ken55,Ishibashi Iwao56,Himi Toshiharu57,Din Jehangir58,Al‐Shammari Ali58,Prasad Abhiram59,Rihal Charanjit S.59,Liu Kan60,Schulze P. Christian61,Bianco Matteo62,Jörg Lucas63,Rickli Hans63,Pestana Gonçalo64,Nguyen Thanh H.65,Böhm Michael50,Maier Lars S.53,Pinto Fausto J.52,Widimský Petr47,Felix Stephan B.4142,Braun‐Dullaeus Ruediger C.66,Rottbauer Wolfgang30,Hasenfuß Gerd24,Pieske Burkert M.1767,Schunkert Heribert2829,Budnik Monika68,Opolski Grzegorz68,Thiele Holger69,Bauersachs Johann36,Horowitz John D.65,Di Mario Carlo70,Bruno Francesco1,Kong William71,Dalakoti Mayank71,Imori Yoichi72,Münzel Thomas13,Crea Filippo39,Lüscher Thomas F.7374,Bax Jeroen J.75,Ruschitzka Frank2,De Ferrari Gaetano Maria1,Fariselli Piero3,Ghadri Jelena R.2,Citro Rodolfo576,D'Ascenzo Fabrizio1,Templin Christian2

Affiliation:

1. Division of Cardiology, Department of Medical Sciences AOU Città della Salute e della Scienza, University of Turin Turin Italy

2. Department of Cardiology, University Heart Center University Hospital Zurich, and University of Zurich Zurich Switzerland

3. Department of Medical Sciences University of Turin Turin Italy

4. Department of Medicine, Surgery and Dentistry University of Salerno Baronissi Italy

5. Department of Vascular Physiopathology IRCCS Neuromed Pozzilli Italy

6. Department of Medicine, Surgery and Pharmacy University of Sassari Sassari Italy

7. Division of Cardiology ‘Antonio Cardarelli’ Hospital Naples Italy

8. Centro Cardiologico Monzino IRCCS Milan Italy

9. Department of Cardiology Kantonsspital Frauenfeld Frauenfeld Switzerland

10. Department of Cardiology Heidelberg University Hospital Heidelberg Germany

11. First Department of Cardiology Medical University of Gdansk Gdansk Poland

12. Division of Cardiology, Angiology and Intensive Medical Care, Department of Internal Medicine III, Mid‐German Heart Center University Hospital Halle, Martin‐Luther‐University Halle‐Wittenberg Halle (Saale) Germany

13. Center for Cardiology Cardiology 1, University Medical Center Mainz Mainz Germany

14. University Hospital for Internal Medicine III (Cardiology and Angiology) Medical University Innsbruck Innsbruck Austria

15. Division of Cardiology Medical University of Graz Graz Austria

16. Heart and Vascular Centre Bad Bevensen Bad Bevensen Germany

17. Department of Cardiology Charité, Campus Rudolf Virchow Berlin Germany

18. Section of Cardiac Electrophysiology, Department of Medicine University of California, San Francisco San Francisco CA USA

19. Keck School of Medicine University of Southern California Los Angeles CA USA

20. TJ Health Partners Heart and Vascular Glasgow KY USA

21. Klinik für Akut‐ und Notfallmedizin St.‐Antonius‐Hospital gGmbH, Akademisches Lehrkrankenhaus der RWTH Aachen Eschweiler Germany

22. Department of Internal Medicine III Heart Center University of Cologne Cologne Germany

23. Krankenhaus ‘Maria Hilf’ Medizinische Klinik Stadtlohn Germany

24. Clinic for Cardiology and Pneumology Georg August University Goettingen Goettingen Germany

25. Vincentius‐Diakonissen Hospital Karlsruhe Germany

26. Department of Intensive Care Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany

27. DZHK (German Centre for Cardiovascular Research) Partner Site Hamburg/Kiel/Luebeck Hamburg Germany

28. Deutsches Herzzentrum München Technische Universität München Munich Germany

29. DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance Munich Germany

30. Department of Internal Medicine II‐Cardiology Medical Center, University of Ulm Ulm Germany

31. Service de Cardiologie Hôpitaux Universitaires de Genève Geneva Switzerland

32. Department of Cardiology John Radcliffe Hospital, Oxford University Hospitals Oxford UK

33. Department of Cardiology Kantonsspital Lucerne Lucerne Switzerland

34. Department of Cardiology Kantonsspital Winterthur Winterthur Switzerland

35. Heart Center Turku University Hospital, University of Turku Turku Finland

36. Department of Cardiology and Angiology Hannover Medical School Hannover Germany

37. Department of Cardiology King's College Hospital London UK

38. Department of Cardiology University Hospital Basel Basel Switzerland

39. Fondazione Policlinico Universitario A. Gemelli IRCCS Catholic University of the Sacred Heart Rome Italy

40. Department of Cardiology Christchurch Hospital Christchurch New Zealand

41. Department of Cardiology and Internal Medicine B University Medicine Greifswald Greifswald Germany

42. DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald Greifswald Germany

43. Department of Cardiology and Cardiac Imaging Center University Hospital of Rangueil Toulouse France

44. Intensive Coronary Care Unit Moscow City Hospital No 1 named after N. Pirogov Moscow Russia

45. First Department of Medicine, Faculty of Medicine University Medical Centre Mannheim (UMM), University of Heidelberg Mannheim Germany

46. DZHK (German Center for Cardiovascular Research) Partner Site, Heidelberg‐Mannheim Mannheim Germany

47. Cardiocenter, Third Faculty of Medicine Charles University in Prague and University Hospital Královské Vinohrady Prague Czech Republic

48. Division of Cardiovascular Medicine, Department of Medicine College of Medicine, University of Florida Gainesville FL USA

49. Department of Internal Medicine I‐Cardiology University Hospital Olomouc Olomouc Czech Republic

50. Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes Homburg/Saar Germany

51. Advanced Heart Failure and Transplantation Center University Medical Center Ljubljana Ljubljana Slovenia

52. CHULN, Center of Cardiology of the University of Lisbon, Lisbon School of Medicine, Lisbon Academic Medical Center Santa Maria University Hospital Lisbon Portugal

53. Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg Regensburg Germany

54. Local Health Unit n. 8, Cardiology Unit Vicenza Italy

55. Department of Cardiovascular Medicine Chiba University Graduate School of Medicine Chiba Japan

56. Department of Cardiology Chiba Emergency Medical Center Chiba Japan

57. Division of Cardiology Kimitsu Central Hospital Kisarazu Japan

58. Dorset Heart Centre Royal Bournemouth Hospital Bournemouth UK

59. Department of Cardiovascular Diseases Mayo Clinic Rochester MN USA

60. Division of Cardiology Heart and Vascular Center, University of Iowa Iowa City IA USA

61. Department of Internal Medicine I University Hospital Jena, Friedrich‐Schiller‐University Jena Jena Germany

62. Division of Cardiology A.O.U. San Luigi Gonzaga Turin Italy

63. Department of Cardiology Kantonsspital St. Gallen St. Gallen Switzerland

64. Department of Cardiology Centro Hospitalar Universitário de São João Porto Portugal

65. Department of Cardiology Basil Hetzel Institute, Queen Elizabeth Hospital, University of Adelaide Adelaide SA Australia

66. Department of Internal Medicine, Cardiology and Angiology Magdeburg University Magdeburg Germany

67. Berlin Institute of Health (BIH) Berlin Germany

68. Department of Cardiology Medical University of Warsaw Warsaw Poland

69. Department of Internal Medicine/Cardiology Heart Center Leipzig, University Hospital Leipzig Germany

70. Structural Interventional Cardiology Careggi University Hospital Florence Italy

71. Department of Cardiology National University Heart Centre Singapore Singapore

72. Department of Cardiovascular Medicine Nippon Medical School Tokyo Japan

73. Center for Molecular Cardiology Schlieren Campus, University of Zurich Zurich Switzerland

74. Royal Brompton and Harefield Hospitals Trust and Imperial College and Kings College London UK

75. Department of Cardiology Leiden University Medical Centre Leiden The Netherlands

76. Department of Cardio‐Thoracic‐Vascular University Hospital San Giovanni di Dio e Ruggi d'Aragona Salerno Italy

Abstract

ABSTRACTAimsTakotsubo 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 resultsA 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.ConclusionA 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.

Publisher

Wiley

Subject

Cardiology and Cardiovascular Medicine

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