Trigger factors in takotsubo syndrome – A systematic review of case reports

Published:March 02, 2019DOI:


      • Trigger factors are common in young females and in males with takotsubo syndrome.
      • Physical is more common than emotional trigger factors in takotsubo syndrome.
      • Physical trigger factors are common in young females with takotsubo syndrome.
      • Physical trigger factors are common in males with takotsubo syndrome.



      Takotsubo syndrome is an acute heart failure syndrome often preceded by a trigger factor of physical or emotional origin, although the proportion is unclear. The aim of the present study was to determine how common different trigger factors are in takotsubo syndrome divided by sex and age in women.

      Material and methods

      The study consisted of a systematic review of all available case reports in PubMed and Web of Science up to March 2018. Trigger factors were categorized into physical and emotional trigger factors.


      Males had to a higher degree experienced a trigger factor (92.6%) compared to females (81.9%, p < .001). Physical trigger factors were most common (67.3%). Males had to a higher degree experienced a physical trigger factor (85.7%) compared to females (63.5%, p < .001). Females ≤50 years of age had to a higher degree experienced a trigger factor (90.8%) compared to females >50 years of age (79.2%, p < .001). Additionally, females ≤50 years of age had to a higher degree experienced a physical trigger factor (75.6%) compared to females >50 years of age (59.3%, p < .01).


      A physical trigger factor is more common than an emotional trigger factor in takotsubo syndrome. Physical triggers includes drugs, surgery and central nervous system conditions. Furthermore, females ≤50 years of age and males more often have an evident trigger factor and it is more often physical, compared to the most common patient, a female >50 years of age.



      βAR (Beta adrenergic receptor), CAD (coronary artery disease), COPD (chronic obstructive pulmonary disease), SNS (sympathetic nervous system)
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        • Sato H.T.H.U.T.
        • Dote K.
        • Ishihara M.
        Tako-tsubo-like left ventricular dysfunction due to multivessel coronary spasm.
        in: Kodama K. Haze K. Hori M. Clinical Aspect of Myocardial Injury: From Ischemia to Heart Failure. Kagakuhyoronsha Publishing, Tokyo1990: 56-64 (In Japanese)
        • Templin C.
        • Ghadri J.R.
        • Diekmann J.
        • Napp L.C.
        • Bataiosu D.R.
        • Jaguszewski M.
        • et al.
        Clinical features and outcomes of Takotsubo (stress) cardiomyopathy.
        N Engl J Med. 2015; 373: 929-938
        • Sharkey S.W.
        • Windenburg D.C.
        • Lesser J.R.
        • Maron M.S.
        • Hauser R.G.
        • Lesser J.N.
        • et al.
        Natural history and expansive clinical profile of stress (Tako-Tsubo) cardiomyopathy.
        J Am Coll Cardiol. 2010; 55: 333-341
        • Prasad A.
        • Lerman A.
        • Rihal C.S.
        Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction.
        Am Heart J. 2008; 155: 408-417
        • Pelliccia F.
        • Greco C.
        • Vitale C.
        • Rosano G.
        • Gaudio C.
        • Kaski J.C.
        Takotsubo syndrome (stress cardiomyopathy): an intriguing clinical condition in search of its identity.
        Am J Med. 2014; 127: 699-704
        • Gianni M.
        • Dentali F.
        • Grandi A.M.
        • Sumner G.
        • Hiralal R.
        • Lonn E.
        Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review.
        Eur Heart J. 2006; 27: 1523-1529
        • Deshmukh A.
        • Kumar G.
        • Pant S.
        • Rihal C.
        • Murugiah K.
        • Mehta J.L.
        Prevalence of Takotsubo cardiomyopathy in the United States.
        Am Heart J. 2012; 164: 66-+
        • Ueyama T.
        Emotional stress-induced Tako-tsubo cardiomyopathy: animal model and molecular mechanism.
        Ann N Y Acad Sci. 2004; 1018: 437-444
        • Said S.M.
        • Saygili E.
        • Rana O.R.
        • Genz C.
        • Hahn J.
        • Bali R.
        • et al.
        Takotsubo cardiomyopathy: what we have learned in the last 25 years? (A comparative literature review).
        Curr Cardiol Rev. 2016; 12: 297-303
        • Lyon A.R.
        • Bossone E.
        • Schneider B.
        • Sechtem U.
        • Citro R.
        • Underwood S.R.
        • et al.
        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. 2016; 18: 8-27
        • Wittstein I.S.
        • Thiemann D.R.
        • Lima J.A.C.
        • Baughman K.L.
        • Schulman S.P.
        • Gerstenblith G.
        • et al.
        Neurohumoral features of myocardial stunning due to sudden emotional stress.
        N Engl J Med. 2005; 352: 539-548
        • Akashi Y.J.
        • Nef H.M.
        • Lyon A.R.
        Epidemiology and pathophysiology of Takotsubo syndrome.
        Nat Rev Cardiol. 2015; 12: 387-397
        • Galiuto L.
        • De Caterina A.R.
        • Porfidia A.
        • Paraggio L.
        • Barchetta S.
        • Locorotondo G.
        • et al.
        Reversible coronary microvascular dysfunction: a common pathogenetic mechanism in apical ballooning or Tako-Tsubo syndrome.
        Eur Heart J. 2010; 31: 1319-1327
        • Tsuchihashi K.
        • Ueshima K.
        • Uchida T.
        • Oh-mura N.
        • Kimura K.
        • Owa M.
        • et al.
        Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina pectoris-myocardial infarction investigations in Japan.
        J Am Coll Cardiol. 2001; 38: 11-18
        • Finsterer J.
        • Stollberger C.
        Neurological and non-neurological triggers of Takotsubo syndrome in the pediatric population.
        Int J Cardiol. 2015; 179: 345-347
        • El-Sayed A.M.
        • Brinjikji W.
        • Salka S.
        Demographic and co-morbid predictors of stress (takotsubo) cardiomyopathy.
        Am J Cardiol. 2012; 110: 1368-1372
        • Agarwal S.
        • Bean M.G.
        • Hata J.S.
        • Castresana M.R.
        Perioperative Takotsubo cardiomyopathy: a systematic review of published cases.
        Semin Cardiothorac Vasc Anesth. 2017; 21: 277-290
        • Pelliccia F.
        • Kaski J.C.
        • Crea F.
        • Camici P.G.
        Pathophysiology of Takotsubo syndrome.
        Circulation. 2017; 135: 2426-2441
        • Patel S.M.
        • Chokka R.G.
        • Prasad K.
        • Prasad A.
        Distinctive clinical characteristics according to age and gender in apical ballooning syndrome (Takotsubo/stress cardiomyopathy): an analysis focusing on men and young women.
        J Card Fail. 2013; 19: 306-310
        • Universitetsbiblioteket
        Svensk MeSH [Internet].
        Karolinska institutet, Stockholm1998 (Available from)
        • Brandspiegel H.Z.
        • Marinchak R.A.
        • Rials S.J.
        • Kowey P.R.
        A broken heart.
        Circulation. 1998; 98: 1349
        • Coen M.
        • Rigamonti F.
        • Roth A.
        • Koessler T.
        Chemotherapy-induced Takotsubo cardiomyopathy, a case report and review of the literature.
        BMC Cancer. 2017; 17: 394
        • Abraham J.
        • Mudd J.O.
        • Kapur N.
        • Klein K.
        • Champion H.C.
        • Wittstein I.S.
        Stress cardiomyopathy after intravenous administration of catecholamines and beta-receptor agonists.
        J Am Coll Cardiol. 2009; 53: 1320-1325
        • Burgdorf C.
        • Kurowski V.
        • Bonnemeier H.
        • Schunkert H.
        • Radke P.W.
        Long-term prognosis of the transient left ventricular dysfunction syndrome (Tako-Tsubo cardiomyopathy): focus on malignancies.
        Eur J Heart Fail. 2008; 10: 1015-1019
        • Schneider B.
        • Athanasiadis A.
        • Stollberger C.
        • Pistner W.
        • Schwab J.
        • Gottwald U.
        • et al.
        Gender differences in the manifestation of tako-tsubo cardiomyopathy.
        Int J Cardiol. 2013; 166: 584-588
        • Bybee K.A.
        • Prasad A.
        Stress-related cardiomyopathy syndromes.
        Circulation. 2008; 118: 397-409
        • Hinojosa-Laborde C.
        • Chapa I.
        • Lange D.
        • Haywood J.R.
        Gender differences in sympathetic nervous system regulation.
        Clin Exp Pharmacol Physiol. 1999; 26: 122-126
        • Sader M.A.
        • Celermajer D.S.
        Endothelial function, vascular reactivity and gender differences in the cardiovascular system.
        Cardiovasc Res. 2002; 53: 597-604
        • Ghadri J.R.
        • Cammann V.L.
        • Jurisic S.
        • Seifert B.
        • Napp L.C.
        • Diekmann J.
        • et al.
        A novel clinical score (InterTAK Diagnostic. Score) to differentiate takotsubo syndrome from acute coronary syndrome: results from the International Takotsubo Registry.
        Eur J Heart Fail. 2017 Aug; 19: 1036-1042