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Clinical Research in Cardiology

, Volume 107, Issue 7, pp 597–606 | Cite as

Prognostic value of N-Terminal Pro-B-Type Natriuretic Peptide in Takotsubo syndrome

  • Thomas Stiermaier
  • Francesco Santoro
  • Tobias Graf
  • Francesca Guastafierro
  • Nicola Tarantino
  • Luisa De Gennaro
  • Pasquale Caldarola
  • Matteo Di Biase
  • Holger Thiele
  • Natale D. Brunetti
  • Christian Möller
  • Ingo Eitel
Original Paper

Abstract

Background

Takotsubo syndrome (TTS), a form of acute transient heart failure, has been associated with severe complications and considerable mortality rates. N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) might serve as a marker to identify high-risk patients but has not yet been investigated regarding prognostic implications in TTS. Aim of this study was to determine the short- and long-term prognostic utility of NT-proBNP in patients with TTS.

Methods

The predictive value of admission NT-proBNP was assessed in an international, multicenter study including 177 consecutive TTS patients. Predefined endpoints were 30-day major adverse cardiac events (MACE) consisting of all-cause death, cardiogenic shock, and pulmonary edema as well as long-term mortality in median 2.3 years after the acute event.

Results

Stratification according to median admission NT-proBNP (4511 pg/ml) resulted in significantly higher 30-day MACE [22.5 versus 9.1%; odds ratio (OR) 2.90, 95% confidence interval (CI) 1.20–6.99 p = 0.015] and long-term mortality rates [16.3 versus 9.4%; hazard ratio (HR) 2.72, 95% CI 1.13–6.56 p = 0.021] in patients > median. The best admission NT-proBNP cutoffs to predict 30-day MACE and long-term mortality were determined at 5560 and 8178 pg/ml respectively, with subsequent improved risk stratification for short-term MACE (OR 3.61, 95% CI 1.49–8.72; p = 0.003) and long-term mortality (HR 4.40; 95% CI 1.85–10.44, p < 0.001). Multivariate regression analysis identified admission NT-proBNP as an independent predictor of 30-day MACE (p < 0.001) and long-term mortality (p = 0.012).

Conclusions

Admission NT-proBNP is an independent predictor for short- and long-term adverse events in TTS patients and, therefore, a useful marker for risk stratification immediately at presentation.

Keywords

Takotsubo syndrome Natriuretic peptides NT-proBNP Prognosis 

Notes

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interest.

Supplementary material

392_2018_1227_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 18 KB)

References

  1. 1.
    Eitel I, von Knobelsdorff-Brenkenhoff F, Bernhardt P, Carbone I, Muellerleile K, Aldrovandi A, Francone M, Desch S, Gutberlet M, Strohm O, Schuler G, Schulz-Menger J, Thiele H, Friedrich MG (2011) Clinical characteristics and cardiovascular magnetic resonance findings in stress (takotsubo) cardiomyopathy. JAMA 306(3):277–286.  https://doi.org/10.1001/jama.2011.992 CrossRefPubMedGoogle Scholar
  2. 2.
    Lyon AR, Bossone E, Schneider B, Sechtem U, Citro R, Underwood SR, Sheppard MN, Figtree GA, Parodi G, Akashi YJ, Ruschitzka F, Filippatos G, Mebazaa A, Omerovic E (2016) Current state of knowledge on Takotsubo syndrome: a position statement from the taskforce on Takotsubo syndrome of the heart failure association of the european society of cardiology. Eur J Heart Fail 18(1):8–27.  https://doi.org/10.1002/ejhf.424 CrossRefPubMedGoogle Scholar
  3. 3.
    Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, Cammann VL, Sarcon A, Geyer V, Neumann CA, Seifert B, Hellermann J, Schwyzer M, Eisenhardt K, Jenewein J, Franke J, Katus HA, Burgdorf C, Schunkert H, Moeller C, Thiele H, Bauersachs J, Tschope C, Schultheiss HP, Laney CA, Rajan L, Michels G, Pfister R, Ukena C, Bohm M, Erbel R, Cuneo A, Kuck KH, Jacobshagen C, Hasenfuss G, Karakas M, Koenig W, Rottbauer W, Said SM, Braun-Dullaeus RC, Cuculi F, Banning A, Fischer TA, Vasankari T, Airaksinen KE, Fijalkowski M, Rynkiewicz A, Pawlak M, Opolski G, Dworakowski R, MacCarthy P, Kaiser C, Osswald S, Galiuto L, Crea F, Dichtl W, Franz WM, Empen K, Felix SB, Delmas C, Lairez O, Erne P, Bax JJ, Ford I, Ruschitzka F, Prasad A, Luscher TF (2015) Clinical features and outcomes of Takotsubo (Stress) cardiomyopathy. N Engl J Med 373(10):929–938.  https://doi.org/10.1056/NEJMoa1406761 CrossRefPubMedGoogle Scholar
  4. 4.
    Stiermaier T, Moeller C, Oehler K, Desch S, Graf T, Eitel C, Vonthein R, Schuler G, Thiele H, Eitel I (2016) Long-term excess mortality in takotsubo cardiomyopathy: predictors, causes and clinical consequences. Eur J Heart Fail 18(6):650–656.  https://doi.org/10.1002/ejhf.494 CrossRefPubMedGoogle Scholar
  5. 5.
    Redfors B, Vedad R, Angeras O, Ramunddal T, Petursson P, Haraldsson I, Ali A, Dworeck C, Odenstedt J, Ioaness D, Libungan B, Shao Y, Albertsson P, Stone GW, Omerovic E (2015) Mortality in Takotsubo syndrome is similar to mortality in myocardial infarction—a report from the SWEDEHEART registry. Int J Cardiol 185:282–289.  https://doi.org/10.1016/j.ijcard.2015.03.162 CrossRefPubMedGoogle Scholar
  6. 6.
    Stiermaier T, Eitel C, Denef S, Desch S, Schuler G, Thiele H, Eitel I (2015) Prevalence and clinical significance of life-threatening arrhythmias in Takotsubo cardiomyopathy. J Am Coll Cardiol 65(19):2148–2150.  https://doi.org/10.1016/j.jacc.2015.02.062 CrossRefPubMedGoogle Scholar
  7. 7.
    Stiermaier T, Eitel C, Desch S, Fuernau G, Schuler G, Thiele H, Eitel I (2016) Incidence, determinants and prognostic relevance of cardiogenic shock in patients with Takotsubo cardiomyopathy. Eur Heart J Acute Cardiovasc Care 5(6):489–496.  https://doi.org/10.1177/2048872615612456 CrossRefPubMedGoogle Scholar
  8. 8.
    Schneider B, Athanasiadis A, Schwab J, Pistner W, Gottwald U, Schoeller R, Toepel W, Winter KD, Stellbrink C, Muller-Honold T, Wegner C, Sechtem U (2014) Complications in the clinical course of tako-tsubo cardiomyopathy. Int J Cardiol 176(1):199–205.  https://doi.org/10.1016/j.ijcard.2014.07.002 CrossRefPubMedGoogle Scholar
  9. 9.
    Singh K, Carson K, Shah R, Sawhney G, Singh B, Parsaik A, Gilutz H, Usmani Z, Horowitz J (2014) Meta-analysis of clinical correlates of acute mortality in Takotsubo cardiomyopathy. Am J Cardiol 113(8):1420–1428.  https://doi.org/10.1016/j.amjcard.2014.01.419 CrossRefPubMedGoogle Scholar
  10. 10.
    Madhavan M, Rihal CS, Lerman A, Prasad A (2011) Acute heart failure in apical ballooning syndrome (TakoTsubo/stress cardiomyopathy): clinical correlates and Mayo Clinic risk score. J Am Coll Cardiol 57(12):1400–1401.  https://doi.org/10.1016/j.jacc.2010.10.038 CrossRefPubMedGoogle Scholar
  11. 11.
    Nunez-Gil IJ, Almendro-Delia M, Andres M, Sionis A, Martin A, Bastante T, Cordoba-Soriano JG, Linares JA, Gonzalez Sucarrats S, Sanchez-Grande-Flecha A, Fabregat-Andres O, Perez B, Escudier-Villa JM, Martin-Reyes R, Perez-Castellanos A, Rueda Sobella F, Cambeiro C, Piqueras-Flores J, Vidal-Perez R, Bodi V, Garcia de la Villa B, Corbi-Pascua M, Biagioni C, Mejia-Renteria HD, Feltes G, Barrabes J, Investigators R (2016) Secondary forms of Takotsubo cardiomyopathy: a whole different prognosis. Eur Heart J Acute Cardiovasc Care 5(4):308–316.  https://doi.org/10.1177/2048872615589512 CrossRefPubMedGoogle Scholar
  12. 12.
    Kagiyama N, Okura H, Tamada T, Imai K, Yamada R, Kume T, Hayashida A, Neishi Y, Kawamoto T, Yoshida K (2016) Impact of right ventricular involvement on the prognosis of Takotsubo cardiomyopathy. Eur Heart J Cardiovasc Imaging 17(2):210–216.  https://doi.org/10.1093/ehjci/jev145 CrossRefPubMedGoogle Scholar
  13. 13.
    Stiermaier T, Adams V, Just M, Blazek S, Desch S, Schuler G, Thiele H, Eitel I (2014) Growth differentiation factor-15 in Takotsubo cardiomyopathy: diagnostic and prognostic value. Int J Cardiol 173(3):424–429.  https://doi.org/10.1016/j.ijcard.2014.03.014 CrossRefPubMedGoogle Scholar
  14. 14.
    Santoro F, Tarantino N, Ferraretti A, Ieva R, Musaico F, Guastafierro F, Di Martino L, Di Biase M, Brunetti ND (2016) Serum interleukin 6 and 10 levels in Takotsubo cardiomyopathy: Increased admission levels may predict adverse events at follow-up. Atherosclerosis 254:28–34.  https://doi.org/10.1016/j.atherosclerosis.2016.09.012 CrossRefPubMedGoogle Scholar
  15. 15.
    Santoro F, Ferraretti A, Musaico F, Di Martino L, Tarantino N, Ieva R, Di Biase M, Brunetti ND (2016) Carbohydrate-antigen-125 levels predict hospital stay duration and adverse events at long-term follow-up in Takotsubo cardiomyopathy. Intern Emerg Med 11(5):687–694.  https://doi.org/10.1007/s11739-016-1393-y CrossRefPubMedGoogle Scholar
  16. 16.
    Frohlich GM, Schoch B, Schmid F, Keller P, Sudano I, Luscher TF, Noll G, Ruschitzka F, Enseleit F (2012) Takotsubo cardiomyopathy has a unique cardiac biomarker profile: NT-proBNP/myoglobin and NT-proBNP/troponin T ratios for the differential diagnosis of acute coronary syndromes and stress induced cardiomyopathy. Int J Cardiol 154(3):328–332.  https://doi.org/10.1016/j.ijcard.2011.09.077 CrossRefPubMedGoogle Scholar
  17. 17.
    Jaguszewski M, Osipova J, Ghadri JR, Napp LC, Widera C, Franke J, Fijalkowski M, Nowak R, Fijalkowska M, Volkmann I, Katus HA, Wollert KC, Bauersachs J, Erne P, Luscher TF, Thum T, Templin C (2014) A signature of circulating microRNAs differentiates Takotsubo cardiomyopathy from acute myocardial infarction. Eur Heart J 35(15):999–1006.  https://doi.org/10.1093/eurheartj/eht392 CrossRefPubMedGoogle Scholar
  18. 18.
    Madhavan M, Borlaug BA, Lerman A, Rihal CS, Prasad A (2009) Stress hormone and circulating biomarker profile of apical ballooning syndrome (Takotsubo cardiomyopathy): insights into the clinical significance of B-type natriuretic peptide and troponin levels. Heart 95(17):1436–1441.  https://doi.org/10.1136/hrt.2009.170399 CrossRefPubMedGoogle Scholar
  19. 19.
    Nguyen TH, Neil CJ, Sverdlov AL, Mahadavan G, Chirkov YY, Kucia AM, Stansborough J, Beltrame JF, Selvanayagam JB, Zeitz CJ, Struthers AD, Frenneaux MP, Horowitz JD (2011) N-terminal pro-brain natriuretic protein levels in takotsubo cardiomyopathy. Am J Cardiol 108(9):1316–1321.  https://doi.org/10.1016/j.amjcard.2011.06.047 CrossRefPubMedGoogle Scholar
  20. 20.
    Ahmed KA, Madhavan M, Prasad A (2012) Brain natriuretic peptide in apical ballooning syndrome (Takotsubo/stress cardiomyopathy): comparison with acute myocardial infarction. Coron Artery Dis 23(4):259–264.  https://doi.org/10.1097/MCA.0b013e3283526a57 CrossRefPubMedGoogle Scholar
  21. 21.
    Santaguida PL, Don-Wauchope AC, Oremus M, McKelvie R, Ali U, Hill SA, Balion C, Booth RA, Brown JA, Bustamam A, Sohel N, Raina P (2014) BNP and NT-proBNP as prognostic markers in persons with acute decompensated heart failure: a systematic review. Heart Fail Rev 19(4):453–470.  https://doi.org/10.1007/s10741-014-9442-y CrossRefPubMedGoogle Scholar
  22. 22.
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Authors/Task Force M (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37(27):2129–2200.  https://doi.org/10.1093/eurheartj/ehw128 CrossRefPubMedGoogle Scholar
  23. 23.
    Prasad A, Lerman A, Rihal CS (2008) Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J 155(3):408–417.  https://doi.org/10.1016/j.ahj.2007.11.008 CrossRefPubMedGoogle Scholar
  24. 24.
    Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG, Hausleiter J, Richardt G, Hennersdorf M, Empen K, Fuernau G, Desch S, Eitel I, Hambrecht R, Fuhrmann J, Bohm M, Ebelt H, Schneider S, Schuler G, Werdan K, Investigators I-SIT. (2012) Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med 367(14):1287–1296.  https://doi.org/10.1056/NEJMoa1208410 CrossRefPubMedGoogle Scholar
  25. 25.
    Charoenpanichkit C, Little WC, Mandapaka S, Dall’Armellina E, Morgan TM, Hamilton CA, Hundley WG (2011) Impaired left ventricular stroke volume reserve during clinical dobutamine stress predicts future episodes of pulmonary edema. J Am Coll Cardiol 57(7):839–848.  https://doi.org/10.1016/j.jacc.2010.10.019 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Santoro F, Ieva R, Musaico F, Ferraretti A, Triggiani G, Tarantino N, Di Biase M, Brunetti ND (2014) Lack of efficacy of drug therapy in preventing takotsubo cardiomyopathy recurrence: a meta-analysis. Clin Cardiol 37(7):434–439.  https://doi.org/10.1002/clc.22280 CrossRefPubMedGoogle Scholar
  27. 27.
    Brunetti ND, Santoro F, De Gennaro L, Correale M, Gaglione A, Di Biase M (2016) Drug treatment rates with beta-blockers and ACE-inhibitors/angiotensin receptor blockers and recurrences in takotsubo cardiomyopathy: a meta-regression analysis. Int J Cardiol 214:340–342.  https://doi.org/10.1016/j.ijcard.2016.03.196 CrossRefPubMedGoogle Scholar
  28. 28.
    Santoro F, Ieva R, Ferraretti A, Ienco V, Carpagnano G, Lodispoto M, Di Biase L, Di Biase M, Brunetti ND (2013) Safety and feasibility of levosimendan administration in takotsubo cardiomyopathy: a case series. Cardiovasc Ther 31(6):e133–e137.  https://doi.org/10.1111/1755-5922.12047 CrossRefGoogle Scholar
  29. 29.
    Möller C, Stiermaier T, Graf T, Eitel C, Thiele H, Burgdorf C, Eitel I (2017) Prevalence and long-term prognostic impact of malignancies in patients with takotsubo syndrome. Eur J Heart Fail.  https://doi.org/10.1002/ejhf.868 (Epub ahead of print) CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Thomas Stiermaier
    • 1
    • 2
  • Francesco Santoro
    • 3
  • Tobias Graf
    • 1
    • 2
  • Francesca Guastafierro
    • 3
  • Nicola Tarantino
    • 3
  • Luisa De Gennaro
    • 4
  • Pasquale Caldarola
    • 4
  • Matteo Di Biase
    • 3
  • Holger Thiele
    • 5
  • Natale D. Brunetti
    • 3
  • Christian Möller
    • 1
    • 2
  • Ingo Eitel
    • 1
    • 2
  1. 1.University Heart Center Lübeck, Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine), University Hospital Schleswig-HolsteinLübeckGermany
  2. 2.German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/LübeckLübeckGermany
  3. 3.Department of Medical and Surgical ScienceUniversity of FoggiaFoggiaItaly
  4. 4.Department of CardiologySan Paolo HospitalBariItaly
  5. 5.Department of Internal Medicine/CardiologyHeart Center Leipzig, University HospitalLeipzigGermany

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