Advertisement

Takotsubo syndrome: an overview of pathophysiology, diagnosis and treatment with emphasis on cancer patients

  • Isabela Bispo Santos da Silva Costa
  • Clara Salles Figueiredo
  • Silvia Moulin Ribeiro Fonseca
  • Cristina Salvadori Bittar
  • Carolina Maria Domingues de Carvalho Silva
  • Stéphanie Itala Rizk
  • Roberto Kalil Filho
  • Ludhmila Abrahão HajjarEmail author
Article

Abstract

Takotsubo syndrome is a disease of great clinical importance that remains underdiagnosed. It is a form of acute heart failure characterized by a transient wall motion abnormality of the left ventricular apex typically triggered by emotional or physical stress. Takotsubo syndrome is commonly associated with cancer and results in poor outcomes. Therefore, early recognition and prompt therapy are essential to improve prognosis. The aim of this manuscript is to review the consequences of the association between cancer and Takotsubo to summarize the available evidence to guide physicians to improve the management of these patients.

Keywords

Takotsubo syndrome Cancer Heart failure 

Notes

References

  1. 1.
    Backhaus T, Fach A, Schmucker J, Fiehn E, Garstka D, Stehmeier J, Hambrecht R, Wienbergen H (2018) Management and predictors of outcome in unselected patients with cardiogenic shock complicating acute ST-segment elevation myocardial infarction: results from the Bremen STEMI registry. Clin Res Cardiol 107(5):371–379Google Scholar
  2. 2.
    Pelliccia F, Kaski JC, Crea F, Camici PG (2017) Pathophysiology of Takotsubo syndrome. Circulation. 135(24):2426–2441Google Scholar
  3. 3.
    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):8–27Google Scholar
  4. 4.
    Medina de Chazal H, Del Buono MG, Keyser-Marcus L, Ma L, Moeller FG, Berrocal D et al (2018) Stress cardiomyopathy diagnosis and treatment. JACC State-of-the-Art Review J Am Coll Cardiol 72(16):1955–1971Google Scholar
  5. 5.
    Ranieri M, Finsterer J, Bedini G, Parati EA, Bersano A (2018) Takotsubo syndrome: clinical features, pathogenesis, treatment, and relationship with cerebrovascular diseases. Curr Neurol Neurosci Rep 18(5):20Google Scholar
  6. 6.
    Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ, Cammann VL, Crea F, Galiuto L, Desmet W, Yoshida T, Manfredini R, Eitel I, Kosuge M, Nef HM, Deshmukh A, Lerman A, Bossone E, Citro R, Ueyama T, Corrado D, Kurisu S, Ruschitzka F, Winchester D, Lyon AR, Omerovic E, Bax JJ, Meimoun P, Tarantini G, Rihal C, Y.-Hassan S, Migliore F, Horowitz JD, Shimokawa H, Lüscher TF, Templin C (2018) International expert consensus document on Takotsubo syndrome (part I): clinical characteristics, diagnostic criteria, and pathophysiology. Eur Heart J 39(22):2032–2046Google Scholar
  7. 7.
    Desai R, Abbas SA, Goyal H, Durairaj A, Fong HK, Hung O, Sachdeva R, Barac A, Yusuf SW, Kumar G (2019) Frequency of Takotsubo cardiomyopathy in adult patients receiving chemotherapy (from a 5-year nationwide inpatient study). Am J Cardiol 123(4):667–673Google Scholar
  8. 8.
    Brunetti ND, Tarantino N, Guastafierro F, De Gennaro L, Correale M, Stiermaier T et al (2019) Malignancies and outcome in Takotsubo syndrome: a meta-analysis study on cancer and stress cardiomyopathy. Heart Fail Rev.  https://doi.org/10.1007/s10741-019-09773-6
  9. 9.
    El-Sayed AM, Brinjikji W, Salka S (2012) Demographic and co-morbid predictors of stress (takotsubo) cardiomyopathy. Am J Cardiol 110(9):1368–1372Google Scholar
  10. 10.
    Burgdorf C, Kurowski V, Bonnemeier H, Schunkert H, Radke PW (2008) Long-term prognosis of the transient left ventricular dysfunction syndrome (Tako-Tsubo cardiomyopathy): focus on malignancies. Eur J Heart Fail 10(10):1015–1019Google Scholar
  11. 11.
    Sattler K, El-Battrawy I, Lang S, Zhou X, Schramm K, Tulumen E et al (2017) Prevalence of cancer in Takotsubo cardiomyopathy: short and long-term outcome. Int J Cardiol 238:159–165Google Scholar
  12. 12.
    Giza DE, Lopez-Mattei J, Vejpongsa P, Munoz E, Iliescu G, Kitkungvan D, Hassan SA, Kim P, Ewer MS, Iliescu C (2017) Stress-induced cardiomyopathy in cancer patients. Am J Cardiol 120(12):2284–2288Google Scholar
  13. 13.
    Girardey M, Jesel L, Campia U, Messas N, Hess S, Imperiale A, Blondet C, Trinh A, Ohlmann P, Morel O (2016) Impact of malignancies in the early and late time course of Takotsubo cardiomyopathy. Circ J 80(10):2192–2198Google Scholar
  14. 14.
    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, Tschöpe C, Schultheiss HP, Laney CA, Rajan L, Michels G, Pfister R, Ukena C, Böhm 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 KEJ, 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, Lüscher TF (2015) Clinical features and outcomes of Takotsubo (stress) cardiomyopathy. N Engl J Med 373(10):929–938Google Scholar
  15. 15.
    Kurisu S, Sato H, Kawagoe T, Ishihara M, Shimatani Y, Nishioka K, Kono Y, Umemura T, Nakamura S (2002) Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J 143(3):448–455Google Scholar
  16. 16.
    Joy PS, Guddati AK, Shapira I (2018) Outcomes of Takotsubo cardiomyopathy in hospitalized cancer patients. J Cancer Res Clin Oncol 144:1539–1545Google Scholar
  17. 17.
    Kawano H, Okada R, Yano K (2003) Histological study on the distribution of autonomic nerves in the human heart. Heart Vessel 18(1):32–39Google Scholar
  18. 18.
    Gagnon N, Mansour S, Bitton Y, Bourdeau I (2017) Takotsubo-like cardiomyopathy in a large cohort of patients with pheochromocytoma and paraganglioma. Endocr Pract 23(10):1178–1192Google Scholar
  19. 19.
    Y-Hassan S (2016) Clinical features and outcome of Pheochromocytoma-induced Takotsubo syndrome: analysis of 80 published cases. Am J Cardiol 117(11):1836–1844Google Scholar
  20. 20.
    Batisse-Lignier M, Pereira B, Motreff P, Pierrard R, Burnot C, Vorilhon C, Maqdasy S, Roche B, Desbiez F, Clerfond G, Citron B, Lusson JR, Tauveron I, Eschalier R (2015) Acute and chronic pheochromocytoma-induced cardiomyopathies: different prognoses?: a systematic analytical review. Medicine (Baltimore) 94(50):e2198Google Scholar
  21. 21.
    Agarwal V, Kant G, Hans N, Messerli FH (2011) Takotsubo-like cardiomyopathy in pheochromocytoma. Int J Cardiol 153(3):241–248Google Scholar
  22. 22.
    Zaghlol R, Kashyap K, Al-Shbool G, Basyal B, Desale S, Campia U et al (2019) Usefulness of malignancy as a predictor of worse in-hospital outcomes in patients with Takotsubo cardiomyopathy. Am J Cardiol 123(6):995–1001Google Scholar
  23. 23.
    Coen M, Rigamonti F, Roth A, Koessler T (2017) Chemotherapy-induced Takotsubo cardiomyopathy, a case report and review of the literature. BMC Cancer 17(1):394Google Scholar
  24. 24.
    Sattler K, El-Battrawy I, Gietzen T, Lang S, Zhou X, Borggrefe M et al (2018) Long term outcome of patients suffering from cancer and Takotsubo syndrome or myocardial infarction. QJM 111(7):473–481Google Scholar
  25. 25.
    Moller C, Stiermaier T, Graf T, Eitel C, Thiele H, Burgdorf C et al (2018) Prevalence and long-term prognostic impact of malignancy in patients with Takotsubo syndrome. Eur J Heart Fail 20(4):816–818Google Scholar
  26. 26.
    Akashi YJ, Nef HM, Lyon AR (2015) Epidemiology and pathophysiology of Takotsubo syndrome. Nat Rev Cardiol 12(7):387–397Google Scholar
  27. 27.
    Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G et al (2005) Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 352(6):539–548Google Scholar
  28. 28.
    Schultz T, Shao Y, Redfors B, Sverrisdottir YB, Ramunddal T, Albertsson P et al (2012) Stress-induced cardiomyopathy in Sweden: evidence for different ethnic predisposition and altered cardio-circulatory status. Cardiology 122(3):180–186Google Scholar
  29. 29.
    Van de Walle SO, Gevaert SA, Gheeraert PJ, De Pauw M, Gillebert TC (2006) Transient stress-induced cardiomyopathy with an “inverted takotsubo” contractile pattern. Mayo Clin Proc 81(11):1499–1502Google Scholar
  30. 30.
    Ovadia D, Esquenazi Y, Bucay M, Bachier CR (2015) Association between takotsubo cardiomyopathy and axitinib: case report and review of the literature. J Clin Oncol 33(1):e1–e3Google Scholar
  31. 31.
    Smith SA, Auseon AJ (2013) Chemotherapy-induced takotsubo cardiomyopathy. Heart Fail Clin 9(2):233–242, x Google Scholar
  32. 32.
    Budnik M, Kucharz J, Wiechno P, Demkow T, Kochanowski J, Gorska E et al (2018) Chemotherapy-induced Takotsubo syndrome. Adv Exp Med Biol.  https://doi.org/10.1007/5584_2018_222
  33. 33.
    Yang S, Asnani A (2018) Cardiotoxicities associated with immune checkpoint inhibitors. Curr Probl Cancer 42(4):422–432Google Scholar
  34. 34.
    Grunwald MR, Howie L, Diaz LA Jr (2012) Takotsubo cardiomyopathy and fluorouracil: case report and review of the literature. J Clin Oncol 30(2):e11–e14Google Scholar
  35. 35.
    Ederhy S, Cautela J, Ancedy Y, Escudier M, Thuny F, Cohen A (2018) Takotsubo-like syndrome in cancer patients treated with immune checkpoint inhibitors. JACC Cardiovasc Imaging 11(8):1187–1190Google Scholar
  36. 36.
    Kinoshita F, Toyokawa G, Tagawa T, Matsubara T, Kozuma Y, Haratake N et al (2018) Takotsubo cardiomyopathy developed after two-stage surgery for double primary lung cancer. Anticancer Res 38(5):2957–2960Google Scholar
  37. 37.
    Modi S, Baig W (2009) Radiotherapy-induced Tako-tsubo cardiomyopathy. Clin Oncol (R Coll Radiol) 21(4):361–362Google Scholar
  38. 38.
    Singh SB, Harle IA (2014) Takotsubo cardiomyopathy secondary in part to cancer-related pain crisis: a case report. J Pain Symptom Manag 48(1):137–142Google Scholar
  39. 39.
    De Gennaro L, Brunetti ND, Ruggiero M, Rutigliano D, Campanella C, Santoro F et al (2015) Vagotonia, cancer, and fluid depletion in Takotsubo cardiomyopathy: the “not” good, the bad and the ugly. Int J Cardiol 179:193–194Google Scholar
  40. 40.
    Kurisu S, Inoue I, Kawagoe T, Ishihara M, Shimatani Y, Nakamura S, Yoshida M, Mitsuba N, Hata T, Sato H (2004) Time course of electrocardiographic changes in patients with tako-tsubo syndrome: comparison with acute myocardial infarction with minimal enzymatic release. Circ J 68(1):77–81Google Scholar
  41. 41.
    Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ, Cammann VL, Crea F, Galiuto L, Desmet W, Yoshida T, Manfredini R, Eitel I, Kosuge M, Nef HM, Deshmukh A, Lerman A, Bossone E, Citro R, Ueyama T, Corrado D, Kurisu S, Ruschitzka F, Winchester D, Lyon AR, Omerovic E, Bax JJ, Meimoun P, Tarantini G, Rihal C, Y.-Hassan S, Migliore F, Horowitz JD, Shimokawa H, Lüscher TF, Templin C (2018) International expert consensus document on Takotsubo syndrome (part II): diagnostic workup, outcome, and management. Eur Heart J 39(22):2047–2062Google Scholar
  42. 42.
    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):1316–1321Google Scholar
  43. 43.
    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):999–1006Google Scholar
  44. 44.
    Kurowski V, Kaiser A, von Hof K, Killermann DP, Mayer B, Hartmann F, Schunkert H, Radke PW (2007) Apical and midventricular transient left ventricular dysfunction syndrome (tako-tsubo cardiomyopathy): frequency, mechanisms, and prognosis. Chest 132(3):809–816Google Scholar
  45. 45.
    El Mahmoud R, Mansencal N, Pilliere R, Leyer F, Abbou N, Michaud P et al (2008) Prevalence and characteristics of left ventricular outflow tract obstruction in Tako-Tsubo syndrome. Am Heart J 156(3):543–548Google Scholar
  46. 46.
    Parodi G, Del Pace S, Salvadori C, Carrabba N, Olivotto I, Gensini GF et al (2007) Left ventricular apical ballooning syndrome as a novel cause of acute mitral regurgitation. J Am Coll Cardiol 50(7):647–649Google Scholar
  47. 47.
    Haghi D, Papavassiliu T, Fluchter S, Kaden JJ, Porner T, Borggrefe M et al (2006) Variant form of the acute apical ballooning syndrome (takotsubo cardiomyopathy): observations on a novel entity. Heart 92(3):392–394Google Scholar
  48. 48.
    Heggemann F, Weiss C, Hamm K, Kaden J, Suselbeck T, Papavassiliu T, Borggrefe M, Haghi D (2009) Global and regional myocardial function quantification by two-dimensional strain in Takotsubo cardiomyopathy. Eur J Echocardiogr 10(6):760–764Google Scholar
  49. 49.
    Heggemann F, Hamm K, Kaelsch T, Sueselbeck T, Papavassiliu T, Borggrefe M, Haghi D (2011) Global and regional myocardial function quantification in Takotsubo cardiomyopathy in comparison to acute anterior myocardial infarction using two-dimensional (2D) strain echocardiography. Echocardiography 28(7):715–719Google Scholar
  50. 50.
    Jordan JH, Todd RM, Vasu S, Hundley WG (2018) Cardiovascular magnetic resonance in the oncology patient. JACC Cardiovasc Imaging 11(8):1150–1172Google Scholar
  51. 51.
    Aikawa Y, Noguchi T, Morita Y, Tateishi E, Kono A, Miura H, Komori Y, Asaumi Y, Fukuda T, Yasuda S (2019) Clinical impact of native T1 mapping for detecting myocardial impairment in takotsubo cardiomyopathy. Eur Heart J Cardiovasc Imaging.  https://doi.org/10.1093/ehjci/jez034
  52. 52.
    Scally C, Abbas H, Ahearn T, Srinivasan J, Mezincescu A, Rudd A, Spath N, Yucel-Finn A, Yuecel R, Oldroyd K, Dospinescu C, Horgan G, Broadhurst P, Henning A, Newby DE, Semple S, Wilson HM, Dawson DK (2019) Myocardial and systemic inflammation in acute stress-induced (Takotsubo) cardiomyopathy. Circulation. 139(13):1581–1592Google Scholar
  53. 53.
    S YH, Tornvall P (2018) Epidemiology, pathogenesis, and management of takotsubo syndrome. Clin Auton Res 28(1):53–65Google Scholar
  54. 54.
    Otalvaro L, Zambrano JP, Fishman JE (2011) Takotsubo cardiomyopathy: utility of cardiac computed tomography angiography for acute diagnosis. J Thorac Imaging 26(3):W83–W85Google Scholar
  55. 55.
    Brunetti ND, Santoro F, De Gennaro L, Correale M, Gaglione A, Di Biase M et al (2017) Combined therapy with beta-blockers and ACE-inhibitors/angiotensin receptor blockers and recurrence of Takotsubo (stress) cardiomyopathy: a meta-regression study. Int J Cardiol 230:281–283Google Scholar
  56. 56.
    Sharkey SW, Pink VR, Lesser JR, Garberich RF, Maron MS, Maron BJ (2015) Clinical profile of patients with high-risk Tako-Tsubo cardiomyopathy. Am J Cardiol 116(5):765–772Google Scholar
  57. 57.
    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–e137Google Scholar
  58. 58.
    Veillet-Chowdhury M, Hassan SF, Stergiopoulos K (2014) Takotsubo cardiomyopathy: a review. Acute Card Care 16(1):15–22Google Scholar
  59. 59.
    Zhang R, Gupta D, Albert SG (2017) Pheochromocytoma as a reversible cause of cardiomyopathy: analysis and review of the literature. Int J Cardiol 249:319–323Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Isabela Bispo Santos da Silva Costa
    • 1
  • Clara Salles Figueiredo
    • 1
  • Silvia Moulin Ribeiro Fonseca
    • 1
  • Cristina Salvadori Bittar
    • 1
  • Carolina Maria Domingues de Carvalho Silva
    • 1
  • Stéphanie Itala Rizk
    • 1
  • Roberto Kalil Filho
    • 1
    • 2
  • Ludhmila Abrahão Hajjar
    • 1
    • 2
    Email author
  1. 1.Department of Cardio-Oncology, Instituto do Câncer do Estado de São Paulo and Instituto do CoracaoFaculdade de Medicina da Universidade de São PauloSão PauloBrazil
  2. 2.Department of CardiologyHospital SirioLibanesSão PauloBrazil

Personalised recommendations