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Broken heart, tako-tsubo or stress cardiomyopathy? Metaphors, meanings and their medical impact

Published:December 22, 2016DOI:https://doi.org/10.1016/j.ijcard.2016.12.129

      Highlights

      • The broken heart syndrome represents a relatively new nosological entity.
      • The broken heart syndrome might trigger cardiac damage and cardiovascular death.
      • The takotsubo syndrome would be a relatively new way of looking at stress-related cardiomyopathy.

      Abstract

      The cardiac impact of psychological stress historically and socially understood as boundary experiences of human life has long since become an icon. From the aching heart to the sudden death provoked by awe, horror, grief, anger, and humiliation on one side and extreme enchantment, enthusiasm, and excitement on the other, the broken heart has become a globally recognized and powerful metaphor present from folklore to popular culture to high literature and back to everyday communication. In medicine, the “broken heart syndrome” is described as a relatively new nosological entity that has been used synonymously with the term tako-tsubo or stress cardiomyopathy. Among those three terms, however, the broken heart most vividly draws the connection between conditions under which lived experience triggers cardiac damage and conversely, cardiovascular death occurs. According to Hassan and Yamasaki (2013) [
      • Y-Hassan S.
      • Yamasaki K.
      History of takotsubo syndrome: is the syndrome really described as a disease entity first in 1990? Some inaccuracies.
      ] and quite apart from the general perception medical notions of the broken heart indeed go back to at least 1967, when Rees and Lutkins studied the death rate among 903 relatives of patients who died in Wales. They found that 4.8% of bereaved close relatives died within a year of bereavement compared with 0.68% of a non-bereaved control group. Among widows and widowers, the mortality rate was even 10 times greater than that of the matched controls. After the first year of bereavement, however, mortality rates of relatives of a deceased person did not differ significantly from the control group Rees and Lutkins (1967) [
      • Rees W.D.
      • Lutkins S.G.
      Mortality of bereavement.
      ]. Similar findings were published by Parkes et al. (1969) [
      • Parkes C.M.
      • Benjamin B.
      • Fitzgerald R.G.
      Broken heart: a statistical study of increased mortality among widowers.
      ] following up on 4486 widowers at the age of 55 for 9 years following the death of their wives in 1957. During the first six months after the spouse had died, the mortality rate of the widowers was 40% above the rate of married men of the same age.
      While it seems plausible to accept the etiological role and pathogenic impact of personal loss, the pathogenic processes causing death remained relatively blurred. We will explain, why inaccurately stressing the fact that the broken heart and/or tako-tsubo syndrome would be a relatively new way of looking at stress-related cardiomyopathy as outlined by Yoshikawa (2015) [
      • Yoshikawa T.
      Takotsubo cardiomyopathy, a new concept of cardiomyopathy: clinical features and pathophysiology.
      ] and why attaching stress-related cardiomyopathy to culturally powerful yet value-laden metaphors, might obstruct pathways to a better understanding, prevention and clinical management of the disease. By looking at narrative understandings and clinical representations of the broken heart, we aim to highlight the need for a more contextualised view of the broken heart syndrome in order to facilitate multi- and transdisciplinary approaches aiming at its prediction, prevention, and treatment.

      Keywords

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      References

        • Y-Hassan S.
        • Yamasaki K.
        History of takotsubo syndrome: is the syndrome really described as a disease entity first in 1990? Some inaccuracies.
        Int. J. Cardiol. 2013; 166: 736-737
        • Rees W.D.
        • Lutkins S.G.
        Mortality of bereavement.
        Br. Med. J. 1967; 4: 13-16
        • Parkes C.M.
        • Benjamin B.
        • Fitzgerald R.G.
        Broken heart: a statistical study of increased mortality among widowers.
        Br. Med. J. 1969; 1: 740-743
        • Yoshikawa T.
        Takotsubo cardiomyopathy, a new concept of cardiomyopathy: clinical features and pathophysiology.
        Int. J. Cardiol. 2015; 182: 297-303
        • Eakin P.J.
        Living Autobiographically: How We Create Identity in Narrative.
        Cornell University Press, Ithaca, N.Y.2008
        • Damasio A.R.
        Descartes' Error : Emotion, Reason, and the Human Brain.
        Penguin, London2005
        • Foer J.S.
        Extremely Loud and Incredibly Close.
        Penguin, New York2006
        • Goldman J.
        Can you die of a broken heart?.
        (BBC online, 2014)
        • T H.
        • Sato H.
        • Dote K.
        • Uchida T.
        • Ishihara M.
        Tako-tsubo-like left ventricular dysfunction due to multivessel coronary spasm.
        in: H. K. Kodama K. Hori M. Clinical Aspect of Myodardial Injury: From Ischemia to Heart Failure. Kagakuhyoronsha Publishing Co., Tokyo1990: 56-64
        • Dote K.
        • Sato H.
        • Tateishi H.
        • Uchida T.
        • Ishihara M.
        Myocardial stunning due to simultaneous multivessel coronary spasms: a review of 5 cases.
        J. Cardiol. 1991; 21: 203-214
        • Kurisu S.
        • Sato H.
        • Kawagoe T.
        • Ishihara M.
        • Shimatani Y.
        • Nishioka K.
        • Kono Y.
        • Umemura T.
        • Nakamura S.
        Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction.
        Am. Heart J. 2002; 143: 448-455
        • Milinis K.
        • Fisher M.
        Takotsubo cardiomyopathy: pathophysiology and treatment.
        Postgrad. Med. J. 2012; 88: 530-538
        • Tsuchihashi K.
        • Ueshima K.
        • Uchida T.
        • Oh-mura N.
        • Kimura K.
        • Owa M.
        • Yoshiyama M.
        • Miyazaki S.
        • Haze K.
        • Ogawa H.
        • Honda T.
        • Hase M.
        • Kai R.
        • Morii I.
        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
        • Desmet W.J.
        • Adriaenssens B.F.
        • Dens J.A.
        Apical ballooning of the left ventricle: first series in white patients.
        Heart. 2003; 89: 1027-1031
        • Previtali M.
        • Repetto A.
        • Panigada S.
        • Camporotondo R.
        • Tavazzi L.
        Left ventricular apical ballooning syndrome: prevalence, clinical characteristics and pathogenetic mechanisms in a European population.
        Int. J. Cardiol. 2009; 134: 91-96
        • Chen C.K.
        • Chang R.Y.
        • Chen C.Y.
        • Chen Y.P.
        • Chu I.T.
        • Liang H.L.
        • Hsu C.T.
        Takotsubo cardiomyopathy as an underlying mediator of myocardial infarction with normal coronary arteries.
        Cardiology. 2010; 115: 186-190
        • Sharkey S.W.
        • Windenburg D.C.
        • Lesser J.R.
        • Maron M.S.
        • Hauser R.G.
        • Lesser J.N.
        • Haas T.S.
        • Hodges J.S.
        • Maron B.J.
        Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy.
        J. Am. Coll. Cardiol. 2010; 55: 333-341
        • Sharkey S.W.
        • Lesser J.R.
        • Maron M.S.
        • Maron B.J.
        Why not just call it tako-tsubo cardiomyopathy: a discussion of nomenclature.
        J. Am. Coll. Cardiol. 2011; 57: 1496-1497
        • Pilgrim T.M.
        • Wyss T.R.
        Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: a systematic review.
        Int. J. Cardiol. 2008; 124: 283-292
        • Kueh S.A.
        • Gabriel R.S.
        • Lund M.
        • Sutton T.
        • Bradley J.
        • Kerr A.J.
        • Looi J.L.
        Clinical characteristics and outcomes of patients with amphetamine-associated cardiomyopathy in South Auckland, New Zealand.
        Heart Lung Circ. 2016; 25: 1087-1093
        • Kurisu S.
        • Inoue I.
        • Kawagoe T.
        • Ishihara M.
        • Shimatani Y.
        • Nakama Y.
        • Kagawa E.
        • Dai K.
        • Ikenaga H.
        Presentation of Tako-tsubo cardiomyopathy in men and women.
        Clin. Cardiol. 2010; 33: 42-45
        • 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
        • 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
        • Singh K.
        • Carson K.
        • Shah R.
        • Sawhney G.
        • Singh B.
        • Parsaik A.
        • Gilutz H.
        • Usmani Z.
        • Horowitz J.
        Meta-analysis of clinical correlates of acute mortality in takotsubo cardiomyopathy.
        Am. J. Cardiol. 2014; 113: 1420-1428
        • Ako J.
        • Sudhir K.
        • Farouque H.M.
        • Honda Y.
        • Fitzgerald P.J.
        Transient left ventricular dysfunction under severe stress: brain-heart relationship revisited.
        Am. J. Med. 2006; 119: 10-17
        • Maron B.J.
        • Towbin J.A.
        • Thiene G.
        • Antzelevitch C.
        • Corrado D.
        • Arnett D.
        • Moss A.J.
        • Seidman C.E.
        • Young J.B.
        Contemporary definitions and classification of the cardiomyopathies: an American Heart Association scientific statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention.
        Circulation. 2006; 113: 1807-1816
        • Azzarelli S.
        • Galassi A.R.
        • Amico F.
        • Giacoppo M.
        • Argentino V.
        • Tomasello S.D.
        • Tamburino C.
        • Fiscella A.
        Clinical features of transient left ventricular apical ballooning.
        Am. J. Cardiol. 2006; 98: 1273-1276
        • Parodi G.
        • Del Pace S.
        • Carrabba N.
        • Salvadori C.
        • Memisha G.
        • Simonetti I.
        • Antoniucci D.
        • Gensini G.F.
        Incidence, clinical findings, and outcome of women with left ventricular apical ballooning syndrome.
        Am. J. Cardiol. 2007; 99: 182-185
        • Manfredini R.
        • Salmi R.
        • Fabbian F.
        • Manfredini F.
        • Gallerani M.
        • Bossone E.
        Breaking heart: chronobiologic insights into takotsubo cardiomyopathy.
        Heart Fail. Clin. 2013; 9 (vii-viii): 147-156
        • Muller J.E.
        • Stone P.H.
        • Turi Z.G.
        • Rutherford J.D.
        • Czeisler C.A.
        • Parker C.
        • Poole W.K.
        • Passamani E.
        • Roberts R.
        • Robertson T.
        • et al.
        Circadian variation in the frequency of onset of acute myocardial infarction.
        N. Engl. J. Med. 1985; 313: 1315-1322
        • Cohen M.C.
        • Rohtla K.M.
        • Lavery C.E.
        • Muller J.E.
        • Mittleman M.A.
        Meta-analysis of the morning excess of acute myocardial infarction and sudden cardiac death.
        Am. J. Cardiol. 1997; 79: 1512-1516
        • Manfredini R.
        • Boari B.
        • Bressan S.
        • Gallerani M.
        • Salmi R.
        • Portaluppi F.
        • Mehta R.H.
        Influence of circadian rhythm on mortality after myocardial infarction: data from a prospective cohort of emergency calls.
        Am. J. Emerg. Med. 2004; 22: 555-559
        • Manfredini F.B.B.S.
        • R
        • et al.
        Circadian variation of cardiovascular events and morning blood pressure surge.
        Vasc. Dis. Prev. 2008; 5: 246-251
        • Nef H.M.
        • Mollmann H.
        • Akashi Y.J.
        • Hamm C.W.
        Mechanisms of stress (Takotsubo) cardiomyopathy.
        Nat. Rev. Cardiol. 2010; 7: 187-193
        • Willich S.N.
        • Lowel H.
        • Lewis M.
        • Hormann A.
        • Arntz H.R.
        • Keil U.
        Weekly variation of acute myocardial infarction. Increased Monday risk in the working population.
        Circulation. 1994; 90: 87-93
        • Gnecchi-Ruscone T.
        • Piccaluga E.
        • Guzzetti S.
        • Contini M.
        • Montano N.
        • Nicolis E.
        Morning and Monday: critical periods for the onset of acute myocardial infarction. The GISSI 2 study experience.
        Eur. Heart J. 1994; 15: 882-887
        • Spielberg C.
        • Falkenhahn D.
        • Willich S.N.
        • Wegscheider K.
        • Voller H.
        Circadian, day-of-week, and seasonal variability in myocardial infarction: comparison between working and retired patients.
        Am. Heart J. 1996; 132: 579-585
        • Witte D.R.
        • Grobbee D.E.
        • Bots M.L.
        • Hoes A.W.
        A meta-analysis of excess cardiac mortality on Monday.
        Eur. J. Epidemiol. 2005; 20: 401-406
        • Barnett A.G.
        • Dobson A.J.
        Excess in cardiovascular events on Mondays: a meta-analysis and prospective study.
        J. Epidemiol. Community Health. 2005; 59: 109-114
        • Murakami S.
        • Otsuka K.
        • Kubo Y.
        • Shinagawa M.
        • Yamanaka T.
        • Ohkawa S.
        • Kitaura Y.
        Repeated ambulatory monitoring reveals a Monday morning surge in blood pressure in a community-dwelling population.
        Am. J. Hypertens. 2004; 17: 1179-1183
        • Ornato J.P.
        • Peberdy M.A.
        • Chandra N.C.
        • Bush D.E.
        Seasonal pattern of acute myocardial infarction in the National Registry of Myocardial Infarction.
        J. Am. Coll. Cardiol. 1996; 28: 1684-1688
        • Manfredini R.
        • Boari B.
        • Smolensky M.H.
        • Salmi R.
        • Gallerani M.
        • Guerzoni F.
        • Guerra V.
        • Maria Malagoni A.
        • Manfredini F.
        Seasonal variation in onset of myocardial infarction--a 7-year single-center study in Italy.
        Chronobiol. Int. 2005; 22: 1121-1135
        • Manfredini R.
        • Manfredini F.
        • Boari B.
        • Bergami E.
        • Mari E.
        • Gamberini S.
        • Salmi R.
        • Gallerani M.
        Seasonal and weekly patterns of hospital admissions for nonfatal and fatal myocardial infarction.
        Am. J. Emerg. Med. 2009; 27: 1097-1103
        • Kurisu S.
        • Inoue I.
        • Kawagoe T.
        • Ishihara M.
        • Shimatani Y.
        • Hata T.
        • Nakama Y.
        • Kijima Y.
        • Kagawa E.
        Circadian variation in the occurrence of tako-tsubo cardiomyopathy: comparison with acute myocardial infarction.
        Int. J. Cardiol. 2007; 115: 270-271
        • Citro R.
        • Previtali M.
        • Bovelli D.
        • Vriz O.
        • Astarita C.
        • Patella M.M.
        • Provenza G.
        • Armentano C.
        • Ciampi Q.
        • Gregorio G.
        • Piepoli M.
        • Bossone E.
        • Manfredini R.
        Chronobiological patterns of onset of Tako-Tsubo cardiomyopathy: a multicenter Italian study.
        J. Am. Coll. Cardiol. 2009; 54: 180-181
        • Abdulla I.
        • Kay S.
        • Mussap C.
        • Nelson G.I.
        • Rasmussen H.H.
        • Hansen P.S.
        • Ward M.R.
        Apical sparing in tako-tsubo cardiomyopathy.
        Intern. Med. J. 2006; 36: 414-418
        • Sharkey S.W.
        • Lesser J.R.
        • Garberich R.F.
        • Pink V.R.
        • Maron M.S.
        • Maron B.J.
        Comparison of circadian rhythm patterns in Tako-tsubo cardiomyopathy versus ST-segment elevation myocardial infarction.
        Am. J. Cardiol. 2012; 110: 795-799
        • Parodi G.
        • Bellandi B.
        • Del Pace S.
        • Barchielli A.
        • Zampini L.
        • Velluzzi S.
        • Carrabba N.
        • Gensini G.F.
        • Antoniucci D.
        Natural history of tako-tsubo cardiomyopathy.
        Chest. 2011; 139: 887-892
        • Manfredini R.
        • Bossone E.
        Tako-tsubo cardiomyopathy: is a temporal pattern of onset confirmed?.
        Chest. 2011; 140 (author reply 1101-1102): 1101
        • Manfredini R.
        • Citro R.
        • Previtali M.
        • Vriz O.
        • Ciampi Q.
        • Pascotto M.
        • Tagliamonte E.
        • Provenza G.
        • Manfredini F.
        • Bossone E.
        Monday preference in onset of takotsubo cardiomyopathy.
        Am. J. Emerg. Med. 2010; 28: 715-719
        • 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
        • Parodi G.
        • Del Pace S.
        • Salvadori C.
        • Carrabba N.
        • Olivotto I.
        • Gensini G.F.
        Left ventricular apical ballooning syndrome as a novel cause of acute mitral regurgitation.
        J. Am. Coll. Cardiol. 2007; 50: 647-649
        • Brunetti N.D.
        • Ieva R.
        • Rossi G.
        • Barone N.
        • De Gennaro L.
        • Pellegrino P.L.
        • Mavilio G.
        • Cuculo A.
        • Di Biase M.
        Ventricular outflow tract obstruction, systolic anterior motion and acute mitral regurgitation in Tako-Tsubo syndrome.
        Int. J. Cardiol. 2008; 127: e152-e157
        • Nef H.M.
        • Mollmann H.
        • Hilpert P.
        • Masseli F.
        • Troidl C.
        • Rolf A.
        • Dill T.
        • Skwara W.
        • Weber M.
        • Hamm C.
        • Elsasser A.
        Severe mitral regurgitation in Tako-Tsubo cardiomyopathy.
        Int. J. Cardiol. 2009; 132: e77-e79
        • Yaghoubi A.R.
        • Ansarin K.
        • Hashemzadeh S.
        • Azhough R.
        • Faraji S.
        • Bozorgi F.
        Tako-tsubo cardiomyopathy induced by emotional stress leading to severe mitral regurgitation, cardiogenic shock and cardiopulmonary arrest.
        Int. J. Cardiol. 2009; 135: e85-e86
        • Syed F.F.
        • Asirvatham S.J.
        • Francis J.
        Arrhythmia occurrence with takotsubo cardiomyopathy: a literature review.
        Europace. 2011; 13: 780-788
        • Dib C.
        • Prasad A.
        • Friedman P.A.
        • Ahmad E.
        • Rihal C.S.
        • Hammill S.C.
        • Asirvatham S.J.
        Malignant arrhythmia in apical ballooning syndrome: risk factors and outcomes.
        Indian Pacing Electrophysiol. J. 2008; 8: 182-192
        • Kida K.
        • Akashi Y.J.
        • Fazio G.
        • Novo S.
        Takotsubo cardiomyopathy.
        Curr. Pharm. Des. 2010; 16: 2910-2917
        • Leurent G.
        • Larralde A.
        • Boulmier D.
        • Fougerou C.
        • Langella B.
        • Ollivier R.
        • Bedossa M.
        • Le Breton H.
        Cardiac MRI studies of transient left ventricular apical ballooning syndrome (takotsubo cardiomyopathy): a systematic review.
        Int. J. Cardiol. 2009; 135: 146-149
        • Otalvaro L.
        • Zambrano J.P.
        • Fishman J.E.
        Takotsubo cardiomyopathy: utility of cardiac computed tomography angiography for acute diagnosis.
        J. Thorac. Imaging. 2011; 26: W83-W85
        • Kurisu S.
        • Inoue I.
        • Kawagoe T.
        • Ishihara M.
        • Shimatani Y.
        • Nishioka K.
        • Umemura T.
        • Nakamura S.
        • Yoshida M.
        • Sato H.
        Myocardial perfusion and fatty acid metabolism in patients with tako-tsubo-like left ventricular dysfunction.
        J. Am. Coll. Cardiol. 2003; 41: 743-748
        • Ito K.
        • Sugihara H.
        • Kinoshita N.
        • Azuma A.
        • Matsubara H.
        Assessment of Takotsubo cardiomyopathy (transient left ventricular apical ballooning) using 99mTc-tetrofosmin, 123I-BMIPP, 123I-MIBG and 99mTc-PYP myocardial SPECT.
        Ann. Nucl. Med. 2005; 19: 435-445
        • Kurisu S.
        • Inoue I.
        • Kawagoe T.
        • Ishihara M.
        • Shimatani Y.
        • Nakama Y.
        • Maruhashi T.
        • Kagawa E.
        • Dai K.
        • Matsushita J.
        • Ikenaga H.
        Prevalence of incidental coronary artery disease in tako-tsubo cardiomyopathy.
        Coron. Artery Dis. 2009; 20: 214-218
      1. H.M. Nef, H. Mollmann, A. Elsasser, Tako-tsubo cardiomyopathy (apical ballooning), Heart 93 (2007) 1309-1315.

        • Grabowski M.
        • Filipiak K.J.
        • Malek L.A.
        • Piatkowski R.
        • Scislo P.
        • Karpinski G.
        • Opolski G.
        Increased B-type natriuretic peptide levels in patients with apical ballooning syndrome - consecutive cases report.
        Int. J. Cardiol. 2008; 124: 404-406
        • Bybee K.A.
        • Prasad A.
        Stress-related cardiomyopathy syndromes.
        Circulation. 2008; 118: 397-409
        • Madhavan M.
        • Borlaug B.A.
        • Lerman A.
        • Rihal C.S.
        • Prasad A.
        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. 2009; 95: 1436-1441
        • 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 M.G.
        Clinical characteristics and cardiovascular magnetic resonance findings in stress (takotsubo) cardiomyopathy.
        JAMA. 2011; 306: 277-286
        • Madhavan M.
        • Rihal C.S.
        • Lerman A.
        • Prasad A.
        Acute heart failure in apical ballooning syndrome (TakoTsubo/stress cardiomyopathy): clinical correlates and Mayo Clinic risk score.
        J. Am. Coll. Cardiol. 2011; 57: 1400-1401
        • Mahadavan G.
        • Nguyen T.H.
        • Horowitz J.D.
        Brain natriuretic peptide: a biomarker for all cardiac disease?.
        Curr. Opin. Cardiol. 2014; 29: 160-166
        • Ennezat P.V.
        • Pesenti-Rossi D.
        • Aubert J.M.
        • Rachenne V.
        • Bauchart J.J.
        • Auffray J.L.
        • Logeart D.
        • Cohen-Solal A.
        • Asseman P.
        Transient left ventricular basal dysfunction without coronary stenosis in acute cerebral disorders: a novel heart syndrome (inverted Takotsubo).
        Echocardiography. 2005; 22: 599-602
        • Van de Walle S.O.
        • Gevaert S.A.
        • Gheeraert P.J.
        • De Pauw M.
        • Gillebert T.C.
        Transient stress-induced cardiomyopathy with an “inverted takotsubo” contractile pattern.
        Mayo Clin. Proc. 2006; 81: 1499-1502
        • Cacciotti L.
        • Camastra G.S.
        • Beni S.
        • Giannantoni P.
        • Musaro S.
        • Proietti I.
        • De Angelis L.
        • Semeraro R.
        • Ansalone G.
        A new variant of Tako-tsubo cardiomyopathy: transient mid-ventricular ballooning.
        J. Cardiovasc. Med. (Hagerstown). 2007; 8: 1052-1054
        • Lyon A.R.
        • Bossone E.
        • Schneider B.
        • Sechtem U.
        • Citro R.
        • Underwood S.R.
        • Sheppard M.N.
        • Figtree G.A.
        • Parodi G.
        • Akashi Y.J.
        • Ruschitzka F.
        • Filippatos G.
        • Mebazaa A.
        • Omerovic E.
        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
        • Stiermaier T.
        • Moeller C.
        • Oehler K.
        • Desch S.
        • Graf T.
        • Eitel C.
        • Vonthein R.
        • Schuler G.
        • Thiele H.
        • Eitel I.
        Long-term excess mortality in takotsubo cardiomyopathy: predictors, causes and clinical consequences.
        Eur. J. Heart Fail. 2016; 18: 650-656
        • Singh K.
        • A. Y.
        • Horowitz J.D.
        Takotsubo syndrome therapy: current status and future directions.
        Int. Cardiovasc. J. 2016; : 23-29
        • Wittstein I.S.
        • Thiemann D.R.
        • Lima J.A.
        • Baughman K.L.
        • Schulman S.P.
        • Gerstenblith G.
        • Wu K.C.
        • Rade J.J.
        • Bivalacqua T.J.
        • Champion H.C.
        Neurohumoral features of myocardial stunning due to sudden emotional stress.
        New Engl. J. Med. 2005; 352: 539-548
        • Yoshioka T.
        • Hashimoto A.
        • Tsuchihashi K.
        • Nagao K.
        • Kyuma M.
        • Ooiwa H.
        • Nozawa A.
        • Shimoshige S.
        • Eguchi M.
        • Wakabayashi T.
        • Yuda S.
        • Hase M.
        • Nakata T.
        • Shimamoto K.
        Clinical implications of midventricular obstruction and intravenous propranolol use in transient left ventricular apical ballooning (Tako-tsubo cardiomyopathy).
        Am. Heart J. 2008; 155: e521-e527
        • Brewington S.D.
        • Abbas A.A.
        • Dixon S.R.
        • Grines C.L.
        • O'Neill W.W.
        Reproducible microvascular dysfunction with dobutamine infusion in Takotsubo cardiomyopathy presenting with ST segment elevation.
        Catheter. Cardiovasc. Interv. 2006; 68: 769-774
        • Abraham J.
        • Mudd J.O.
        • Kapur N.K.
        • 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
        • Naredi S.
        • Lambert G.
        • Eden E.
        • Zall S.
        • Runnerstam M.
        • Rydenhag B.
        • Friberg P.
        Increased sympathetic nervous activity in patients with nontraumatic subarachnoid hemorrhage.
        Stroke. 2000; 31: 901-906
        • Takizawa M.
        • Kobayakawa N.
        • Uozumi H.
        • Yonemura S.
        • Kodama T.
        • Fukusima K.
        • Takeuchi H.
        • Kaneko Y.
        • Kaneko T.
        • Fujita K.
        • Honma Y.
        • Aoyagi T.
        A case of transient left ventricular ballooning with pheochromocytoma, supporting pathogenetic role of catecholamines in stress-induced cardiomyopathy or takotsubo cardiomyopathy.
        Int. J. Cardiol. 2007; 114: e15-e17
        • Ellison G.M.
        • Torella D.
        • Karakikes I.
        • Purushothaman S.
        • Curcio A.
        • Gasparri C.
        • Indolfi C.
        • Cable N.T.
        • Goldspink D.F.
        • Nadal-Ginard B.
        Acute beta-adrenergic overload produces myocyte damage through calcium leakage from the ryanodine receptor 2 but spares cardiac stem cells.
        J. Biol. Chem. 2007; 282: 11397-11409
        • Lyon A.R.
        • Rees P.S.
        • Prasad S.
        • Poole-Wilson P.A.
        • Harding S.E.
        Stress (Takotsubo) cardiomyopathy--a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning.
        Nat. Clin. Pract. Cardiovasc. Med. 2008; 5: 22-29
        • Uchida Y.
        • Egami H.
        • Sakurai T.
        • Kanai M.
        • Shirai S.
        • Nakagawa O.
        • Oshima T.
        Possible participation of endothelial cell apoptosis of coronary microvessels in the genesis of Takotsubo cardiomyopathy.
        Clin. Cardiol. 2010; 33: 371-377
        • Nef H.M.
        • Mollmann H.
        • Kostin S.
        • Troidl C.
        • Voss S.
        • Weber M.
        • Dill T.
        • Rolf A.
        • Brandt R.
        • Hamm C.W.
        • Elsasser A.
        Tako-Tsubo cardiomyopathy: intraindividual structural analysis in the acute phase and after functional recovery.
        Eur. Heart J. 2007; 28: 2456-2464
        • Ueyama T.
        • Kawabe T.
        • Hano T.
        • Tsuruo Y.
        • Ueda K.
        • Ichinose M.
        • Kimura H.
        • Yoshida K.
        Upregulation of heme oxygenase-1 in an animal model of Takotsubo cardiomyopathy.
        Circ. J. 2009; 73: 1141-1146
        • Bybee K.A.
        • Murphy J.
        • Prasad A.
        • Wright R.S.
        • Lerman A.
        • Rihal C.S.
        • Chareonthaitawee P.
        Acute impairment of regional myocardial glucose uptake in the apical ballooning (takotsubo) syndrome.
        J. Nucl. Cardiol. 2006; 13: 244-250
        • Ueyama T.
        • Hano T.
        • Kasamatsu K.
        • Yamamoto K.
        • Tsuruo Y.
        • Nishio I.
        Estrogen attenuates the emotional stress-induced cardiac responses in the animal model of Tako-tsubo (Ampulla) cardiomyopathy.
        J. Cardiovasc. Pharmacol. 2003; 42: S117-S119
        • Ibanez B.
        • Navarro F.
        • Cordoba M.
        • Farre M.A.P.J.
        Tako-tsubo transient left ventricular apical ballooning: is intravascular ultrasound the key to resolve the enigma?.
        Heart. 2005; 91: 102-104
        • Lindsay J.
        • Paixao A.
        • Chao T.
        • Pichard A.D.
        Pathogenesis of the Takotsubo syndrome: a unifying hypothesis.
        Am. J. Cardiol. 2010; 106: 1360-1363
        • Cherian J.
        • Angelis D.
        • Filiberti A.
        • Saperia G.
        Can takotsubo cardiomyopathy be familial?.
        Int. J. Cardiol. 2007; 121: 74-75
        • Kleinfeldt T.
        • Severin R.
        • Lischke S.
        • Ince H.
        • Nienaber C.A.
        Recurrent left ventricular apical ballooning induced by recurrent stress.
        Int. J. Cardiol. 2009; 134: e47-e48
        • Pison L.
        • De Vusser P.
        • Mullens W.
        Apical ballooning in relatives.
        Heart. 2004; 90e67
        • Kumar G.
        • Holmes Jr., D.R.
        • Prasad A.
        “Familial” apical ballooning syndrome (Takotsubo cardiomyopathy).
        Int. J. Cardiol. 2010; 144: 444-445
        • Limongelli G.
        • D'Alessandro R.
        • Masarone D.
        • Maddaloni V.
        • Vriz O.
        • Minisini R.
        • Citro R.
        • Calabro P.
        • Russo M.G.
        • Calabro R.
        • Pacileo G.
        • Bossone E.
        • Elliott P.M.
        Takotsubo cardiomyopathy: do the genetics matter?.
        Heart Fail. Clin. 2013; 9 (ix): 207-216
        • Sharkey S.W.
        • Maron B.J.
        • Nelson P.
        • Parpart M.
        • Maron M.S.
        • Bristow M.R.
        Adrenergic receptor polymorphisms in patients with stress (tako-tsubo) cardiomyopathy.
        J. Cardiol. 2009; 53: 53-57
        • Vriz O.
        • Minisini R.
        • Citro R.
        • Guerra V.
        • Zito C.
        • De Luca G.
        • Pavan D.
        • Pirisi M.
        • Limongelli G.
        • Bossone E.
        Analysis of beta1 and beta2-adrenergic receptors polymorphism in patients with apical ballooning cardiomyopathy.
        Acta Cardiol. 2011; 66: 787-790
        • Spinelli L.
        • Trimarco V.
        • Di Marino S.
        • Marino M.
        • Iaccarino G.
        • Trimarco B.
        L41Q polymorphism of the G protein coupled receptor kinase 5 is associated with left ventricular apical ballooning syndrome.
        Eur. J. Heart Fail. 2010; 12: 13-16
        • Zaroff J.G.
        • Pawlikowska L.
        • Miss J.C.
        • Yarlagadda S.
        • Ha C.
        • Achrol A.
        • Kwok P.Y.
        • McCulloch C.E.
        • Lawton M.T.
        • Ko N.
        • Smith W.
        • Young W.L.
        Adrenoceptor polymorphisms and the risk of cardiac injury and dysfunction after subarachnoid hemorrhage.
        Stroke. 2006; 37: 1680-1685
        • Handy A.D.
        • Prasad A.
        • Olson T.M.
        Investigating genetic variation of adrenergic receptors in familial stress cardiomyopathy (apical ballooning syndrome).
        J. Cardiol. 2009; 54: 516-517
        • Kleinfeldt T.
        • Schneider H.
        • Akin I.
        • Kische S.
        • Gokmen Turan R.
        • Nienaber C.A.
        • Ince H.
        Detection of FMR1-gene in Takotsubo cardiomyopathy: a new piece in the puzzle.
        Int. J. Cardiol. 2009; 137: e81-e83
        • Kushiro T.
        • Saito F.
        • Kusama J.
        • Takahashi H.
        • Imazeki T.
        • Tani S.
        • Kikuchi S.
        • Imai S.
        • Matsudaira K.
        • Watanabe I.
        • Hino T.
        • Sato Y.
        • Nakayama T.
        • Nagao K.
        • Kanmatsuse K.
        Takotsubo-shaped cardiomyopathy with type I CD36 deficiency.
        Heart Vessel. 2005; 20: 123-125
        • Nef H.M.
        • Mollmann H.
        • Troidl C.
        • Kostin S.
        • Bottger T.
        • Voss S.
        • Hilpert P.
        • Krause N.
        • Weber M.
        • Rolf A.
        • Dill T.
        • Schaper J.
        • Hamm C.W.
        • Elsasser A.
        Expression profiling of cardiac genes in Tako-Tsubo cardiomyopathy: insight into a new cardiac entity.
        J. Mol. Cell. Cardiol. 2008; 44: 395-404
        • Bang D.W.
        • Chung J.W.
        • Hyon M.S.
        • Kim S.K.
        • Kwon Y.J.
        Proteomic analysis of serum in patients with apical ballooning syndrome.
        Int. J. Cardiol. 2011; 146: 118-119
        • Migliore F.
        • Bilato C.
        • Isabella G.
        • Iliceto S.
        • Tarantini G.
        Haemodynamic effects of acute intravenous metoprolol in apical ballooning syndrome with dynamic left ventricular outflow tract obstruction.
        Eur. J. Heart Fail. 2010; 12: 305-308
        • Palecek T.
        • Kuchynka P.
        • Linhart A.
        Treatment of Takotsubo cardiomyopathy.
        Curr. Pharm. Des. 2010; 16: 2905-2909
        • Prasad A.
        Apical ballooning syndrome: an important differential diagnosis of acute myocardial infarction.
        Circulation. 2007; 115: e56-e59
        • Konety S.H.
        • Horwitz P.
        • Lindower P.
        • Olshansky B.
        Arrhythmias in tako-tsubo syndrome--benign or malignant?.
        Int. J. Cardiol. 2007; 114: 141-144
        • Akashi Y.J.
        • Goldstein D.S.
        • Barbaro G.
        • Ueyama T.
        Takotsubo cardiomyopathy: a new form of acute, reversible heart failure.
        Circulation. 2008; 118: 2754-2762
        • Fazio G.
        • Pizzuto C.
        • Barbaro G.
        • Sutera L.
        • Incalcaterra E.
        • Evola G.
        • Azzarelli S.
        • Palecek T.
        • Di Gesaro G.
        • Cascio C.
        • Novo G.
        • Akashi Y.J.
        • Novo S.
        Chronic pharmacological treatment in takotsubo cardiomyopathy.
        Int. J. Cardiol. 2008; 127: 121-123
        • Palecek T.
        • Linhart A.
        • Jansa P.
        • Lubanda J.C.
        • Belohlavek J.
        • Humhal J.
        • Susa Z.
        • Aschermann M.
        Takotsubo cardiomyopathy: case report and literature review.
        Cas. Lek. Cesk. 2005; 144 (discussion 408-409): 405-408
        • Wang X.R.
        • Xiao J.
        • Sun D.J.
        Myocardial protective effects of electroacupuncture and hypothermia on porcine heart after ischemia/reperfusion.
        Acupunct. Electrother. Res. 2003; 28: 193-200
        • Wang X.R.
        • Lin H.
        • Wang Z.H.
        Protective effects of electroacupuncture and Salviae miltiorrhizae on myocardial ischemia/reperfusion in rabbits.
        Acupunct. Electrother. Res. 2003; 28: 175-182
        • Tsou M.T.
        • Huang C.H.
        • Chiu J.H.
        Electroacupuncture on PC6 (Neiguan) attenuates ischemia/reperfusion injury in rat hearts.
        Am. J. Chin. Med. 2004; 32: 951-965
        • Gao J.
        • Fu W.
        • Jin Z.
        • Yu X.
        A preliminary study on the cardioprotection of acupuncture pretreatment in rats with ischemia and reperfusion: involvement of cardiac beta-adrenoceptors.
        J. Physiol. Sci. 2006; 56: 275-279
        • Longhurst J.C.
        Electroacupuncture treatment of arrhythmias in myocardial ischemia.
        Am. J. Physiol. Heart Circ. Physiol. 2007; 292: H2032-H2034
        • Zhang H.
        • Liu L.
        • Huang G.
        • Zhou L.
        • Wu W.
        • Zhang T.
        • Huang H.
        Protective effect of electroacupuncture at the Neiguan point in a rabbit model of myocardial ischemia-reperfusion injury.
        Can. J. Cardiol. 2009; 25: 359-363
        • Cao J.
        • Zhou M.Q.
        • Wu S.B.
        • Wang K.M.
        • Zhou Y.P.
        • Wang Y.L.
        • Chen Y.N.
        Effects of acupuncture on expression of norepinephrine transporter mRNA in the cervical sympathetic ganglion and beta1-AR mRNA in the heart in cerebral-cardiac syndrome rats.
        Zhen Ci Yan Jiu. 2011; 36: 252-257
        • Yuan S.M.
        • Jing H.
        Insights into the monomers and single drugs of Chinese herbal medicine on myocardial preservation.
        Afr. J. Tradit. Complement. Altern. Med. 2011; 8: 104-127
        • Jiang Z.
        • Chai J.
        • Chuang H.H.
        • Li S.
        • Wang T.
        • Cheng Y.
        • Chen W.
        • Zhou D.
        Artesunate induces G0/G1 cell cycle arrest and iron-mediated mitochondrial apoptosis in A431 human epidermoid carcinoma cells.
        Anti-Cancer Drugs. 2012; 23: 606-613
        • Mao Z.G.
        • Zhou J.
        • Wang H.
        • He D.S.
        • Xiao W.W.
        • Liao G.Z.
        • Qiu L.B.
        • Zhu Y.H.
        • Wang H.J.
        Artesunate inhibits cell proliferation and decreases growth hormone synthesis and secretion in GH3 cells.
        Mol. Biol. Rep. 2012; 39: 6227-6234
        • Redington K.L.
        • Disenhouse T.
        • Li J.
        • Wei C.
        • Dai X.
        • Gladstone R.
        • Manlhiot C.
        • Redington A.N.
        Electroacupuncture reduces myocardial infarct size and improves post-ischemic recovery by invoking release of humoral, dialyzable, cardioprotective factors.
        J. Physiol. Sci. 2013; 63: 219-223
        • Dow J.
        • Painovich J.
        • Hale S.L.
        • Tjen A.L.S.
        • Longhurst J.C.
        • Kloner R.A.
        Absence of actions of commonly used Chinese herbal medicines and electroacupuncture on myocardial infarct size.
        J. Cardiovasc. Pharmacol. Ther. 2012; 17: 403-411
        • Mao H.
        • Gu H.
        • Qu X.
        • Sun J.
        • Song B.
        • Gao W.
        • Liu J.
        • Shao Q.
        Involvement of the mitochondrial pathway and Bim/Bcl-2 balance in dihydroartemisinin-induced apoptosis in human breast cancer in vitro.
        Int. J. Mol. Med. 2013; 31: 213-218