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Beta-blockers are associated with better long-term survival in patients with Takotsubo syndrome
  1. Angelo Silverio1,
  2. Guido Parodi2,
  3. Fernando Scudiero3,
  4. Eduardo Bossone4,
  5. Marco Di Maio1,
  6. Olga Vriz5,
  7. Michele Bellino1,
  8. Concetta Zito6,
  9. Gennaro Provenza7,
  10. Ilaria Radano7,
  11. Cesare Baldi7,
  12. Antonello D'Andrea8,
  13. Giuseppina Novo9,
  14. Ciro Mauro4,
  15. Fausto Rigo10,
  16. Pasquale Innelli11,
  17. Jorge Salerno-Uriarte12,
  18. Matteo Cameli13,
  19. Carmine Vecchione1,14,
  20. Francesco Antonini Canterin15,
  21. Gennaro Galasso1,
  22. Rodolfo Citro7,14
  1. 1 Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi (Salerno), Italy
  2. 2 Department of Cardiology, ASL4 Liguria, Lavagna, Italy
  3. 3 Cardiology Department, Azienda Ospedaliera Bolognini Seriate, Seriate, Italy
  4. 4 Department of Cardiology, Antonio Cardarelli Hospital, Naples, Italy
  5. 5 Cardiology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  6. 6 Department of Clinical and Experimental Medicine - Cardiology, University of Messina, Messina, Italy
  7. 7 Cardiovascular Department, Azienda Ospedaliera Universitaria 'San Giovanni di Dio e Ruggi d'Aragona', Salerno, Italy
  8. 8 Department of Cardiology, Umberto I Hospital, Nocera Inferiore, Italy
  9. 9 Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza (PROMISE), Università degli Studi di Palermo, Palermo, Italy
  10. 10 Department of Cardiology, Ospedale dell'Angelo Mestre-Venice, Mestre, Italy
  11. 11 Department of Cardiovascular Imaging, San Carlo Hospital, Potenza, Italy
  12. 12 Department of Cardiology, University of Insubria, Varese, Italy
  13. 13 Department of Medical Biotechnologies, University of Siena, Siena, Italy
  14. 14 Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy
  15. 15 Department of Cardiology, High Specialization Rehabilitation Hospital Motta di Livenza, Motta di Livenza, Italy
  1. Correspondence to Dr Rodolfo Citro, Cardiovascular, Azienda Ospedaliera Universitaria 'San Giovanni di Dio e Ruggi d'Aragona', Salerno, 84125, Italy; rodolfocitro{at}


Objective The advantage of beta-blockers has been postulated in patients with Takotsubo syndrome (TTS) given the pathophysiological role of catecholamines. We hypothesised that beta-blocker treatment after discharge may improve the long-term clinical outcome in this patient population.

Methods This was an observational, multicentre study including consecutive patients with TTS diagnosis prospectively enrolled in the Takotsubo Italian Network (TIN) register from January 2007 to December 2018. TTS was diagnosed according to the TIN, Heart Failure Association and InterTAK Diagnostic Criteria. The primary study outcome was the occurrence of all-cause death at the longest available follow-up; secondary outcomes were TTS recurrence, cardiac and non-cardiac death.

Results The study population included 825 patients (median age: 72.0 (63.0–78.0) years; 91.9 % female): 488 (59.2%) were discharged on beta-blockers and 337 (40.8%) without beta-blockers. The median follow-up was 24.0 months. The adjusted Cox regression analysis showed a significantly lower risk for all-cause death (adjusted HR: 0.563; 95% CI: 0.356 to 0.889) and non-cardiac death (adjusted HR: 0.525; 95% CI: 0.309 to 0.893) in patients receiving versus those not receiving beta-blockers, but no significant differences in terms of TTS recurrence (adjusted HR: 0.607; 95% CI: 0.311 to 1.187) and cardiac death (adjusted HR: 0.699; 95% CI: 0.284 to 1.722). The positive survival effect of beta-blockers was higher in patients with hypertension than in those without (pinteraction=0.014), and in patients who developed cardiogenic shock during the acute phase than in those who did not (pinteraction=0.047).

Conclusions In this real-world register population, beta-blockers were associated with a significantly higher long-term survival, particularly in patients with hypertension and in those who developed cardiogenic shock during the acute phase.

  • Hypertension
  • Outcome Assessment, Health Care
  • Cardiomyopathies

Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information.

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  • Contributors AS, RC, CB, FR, PI and FAC have contributed to the planning of the work. AS, GP, EB, AD’A, GN, CM, MDM, OV, CZ, GP, IR, JS-U, MC, CV and RC have contributed to the conduct of the work. AS, RC, FS, MB and GG have contributed to reporting the work. AS and MDM performed the statistical analysis. RC and GP have critically revised the manuscript. RC and AS accepts full responsibility for the work and/or the conduct of the study.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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