{{Short description|Sudden temporary weakening of the heart muscle}} {{Use dmy dates|date=September 2019}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox medical condition | name = Takotsubo cardiomyopathy | image = TakoTsubo scheme.png | caption = Schematic representation of cardiomyopathy (A) compared to a normal heart (B) | field = Cardiology | synonyms = Transient apical ballooning syndrome,<ref name="pmid18599137">{{cite journal | vauthors = Eshtehardi P, Koestner SC, Adorjan P, Windecker S, Meier B, Hess OM, Wahl A, Cook S | title = Transient apical ballooning syndrome--clinical characteristics, ballooning pattern, and long-term follow-up in a Swiss population | journal = International Journal of Cardiology | volume = 135 | issue = 3 | pages = 370–375 | date = July 2009 | pmid = 18599137 | doi = 10.1016/j.ijcard.2008.03.088 }}</ref> apical ballooning cardiomyopathy,<ref name="pmid18678857">{{cite journal | vauthors = Bergman BR, Reynolds HR, Skolnick AH, Castillo D | title = A case of apical ballooning cardiomyopathy associated with duloxetine | journal = Annals of Internal Medicine | volume = 149 | issue = 3 | pages = 218–219 | date = August 2008 | pmid = 18678857 | doi = 10.7326/0003-4819-149-3-200808050-00021 | doi-access = }}</ref> stress-induced cardiomyopathy, broken-heart syndrome, Gebrochenes-Herz syndrome<ref name="Openstax Anatomy & Physiology attribution">{{cite book| vauthors = Betts JG, Desaix P, Johnson E, Johnson JE, Korol O, Kruse D, Poe B, Wise J, Womble MD, Young KA |title=Anatomy & Physiology|url= https://openstax.org/books/anatomy-and-physiology/pages/19-4-cardiac-physiology|location=Houston|publisher=OpenStax CNX|isbn=978-1-947172-04-3|date=July 29, 2023|at=19.4 Cardiac Physiology}}</ref> | symptoms = | complications = | onset = | duration = Typically a few days, up to a few months | types = | causes = | risks = Physical stress (e.g., sepsis, chemotherapy), psychological stress (e.g., loss of employment, sudden loss of relationship, grief, anxiety), genetic predisposition | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = Good | frequency = | deaths = }} <!-- Definition and symptoms -->
'''Takotsubo cardiomyopathy''' or '''takotsubo syndrome''' ('''TTS'''), also known as '''stress cardiomyopathy''', is a type of non-ischemic cardiomyopathy in which there is a sudden temporary weakening of the muscular portion of the heart.<ref>{{cite book| vauthors = Zamir M |title=The Physics of Coronary Blood Flow|date=2005|publisher=Springer Science and Business Media|isbn=978-0387-25297-1|page=387|url=https://books.google.com/books?id=BuokLwrks2MC&q=broken+heart+syndrome+journal&pg=PA387}}</ref> It usually appears after a significant stressor, either physical or emotional; when caused by the latter, the condition is sometimes called '''broken heart syndrome'''.<ref>{{cite news|title=Mayo Clinic Research Reveals 'Broken Heart Syndrome' Recurs in 1 of 10 Patients|url=http://www.medicalnewstoday.com/releases/56666.php|newspaper=Medical News Today|publisher=MediLexicon International Ltd}}</ref>
<!--Mechanism & Diagnosis --> Examples of physical stressors that can cause TTS are sepsis, shock, subarachnoid hemorrhage, and pheochromocytoma. Emotional stressors include bereavement, divorce, or the loss of a job.<ref name="Ghadri_2018" /> Reviews suggest that of patients diagnosed with the condition, about 70–80% recently experienced a major stressor, including 41–50% with a physical stressor and 26–30% with an emotional stressor.<ref>{{cite journal | vauthors = Sanchez-Jimenez EF | title = Initial clinical presentation of Takotsubo cardiomyopathy with-a focus on electrocardiographic changes: A literature review of cases | journal = World Journal of Cardiology | volume = 5 | issue = 7 | pages = 228–241 | date = July 2013 | pmid = 23888192 | pmc = 3722420 | doi = 10.4330/wjc.v5.i7.228 | doi-access = free }}</ref><ref name="Eitel_2011">{{cite journal | vauthors = 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 | title = Clinical characteristics and cardiovascular magnetic resonance findings in stress (takotsubo) cardiomyopathy | journal = JAMA | volume = 306 | issue = 3 | pages = 277–286 | date = July 2011 | pmid = 21771988 | doi = 10.1001/jama.2011.992 | doi-access = }}</ref> TTS can also appear in patients who have not experienced major stressors.<ref name="Eitel_2011" /><ref name="Templin_2015">{{cite journal | vauthors = 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 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, Lüscher TF | title = Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy | journal = The New England Journal of Medicine | volume = 373 | issue = 10 | pages = 929–938 | date = September 2015 | pmid = 26332547 | doi = 10.1056/NEJMoa1406761 }}</ref>
The pathophysiology is not well understood, but a sudden massive surge of catecholamines such as adrenaline and noradrenaline from extreme stress or a tumor secreting these chemicals is thought to play a central role.<ref name="Tavazzi2017">{{cite journal | vauthors = Tavazzi G, Zanierato M, Via G, Iotti GA, Procaccio F | title = Are Neurogenic Stress Cardiomyopathy and Takotsubo Different Syndromes With Common Pathways?: Etiopathological Insights on Dysfunctional Hearts | journal = JACC. Heart Failure | volume = 5 | issue = 12 | pages = 940–942 | date = December 2017 | pmid = 29191302 | doi = 10.1016/j.jchf.2017.09.006 | doi-access = free }}</ref> Excess catecholamines, when released directly by nerves that stimulate cardiac muscle cells, have a toxic effect and can lead to decreased cardiac muscular function or "stunning".<ref name="Akashi2015" /><ref name="Pelliccia2017">{{cite journal | vauthors = Pelliccia F, Kaski JC, Crea F, Camici PG | title = Pathophysiology of Takotsubo Syndrome | journal = Circulation | volume = 135 | issue = 24 | pages = 2426–2441 | date = June 2017 | pmid = 28606950 | doi = 10.1161/CIRCULATIONAHA.116.027121 | s2cid = 207581288 | doi-access = free }}</ref> Further, this adrenaline surge triggers the arteries to tighten, thereby raising blood pressure and placing more stress on the heart, and may lead to spasm of the coronary arteries that supply blood to the heart muscle.<ref name="Tavazzi2017"/> This impairs the arteries from delivering adequate blood flow and oxygen to the heart muscle.<ref name="Tavazzi2017"/> Together, these events can lead to congestive heart failure and decrease the heart's output of blood with each squeeze.<ref name="Tavazzi2017"/>
<!-- Epidemiology and culture--> Takotsubo cardiomyopathy occurs worldwide.<ref name="Akashi2015">{{cite journal | vauthors = Akashi YJ, Nef HM, Lyon AR | title = Epidemiology and pathophysiology of Takotsubo syndrome | journal = Nature Reviews. Cardiology | volume = 12 | issue = 7 | pages = 387–397 | date = July 2015 | pmid = 25855605 | doi = 10.1038/nrcardio.2015.39 | hdl-access = free | s2cid = 24742760 | hdl = 10044/1/25730 }}</ref> The condition is thought to be responsible for 2% of all acute coronary syndrome cases presenting to hospitals.<ref name="Akashi2015"/> Although TTS has generally been considered a self-limiting disease, spontaneously resolving over the course of days to weeks, contemporary observations show that "a subset of TTS patients may present with symptoms arising from its complications, e.g. heart failure, pulmonary edema, stroke, cardiogenic shock, or cardiac arrest". This does not imply that rates of shock/death of TTS are comparable to those of acute coronary syndrome, but that patients with acute complications may co-occur with TTS.<ref name="Ghadri_2018">{{cite journal | vauthors = 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 | title = International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology | journal = European Heart Journal | volume = 39 | issue = 22 | pages = 2032–2046 | date = June 2018 | pmid = 29850871 | pmc = 5991216 | doi = 10.1093/eurheartj/ehy076 }}</ref> These cases of shock and death have been associated with the occurrence of TTS secondary to an inciting physical stressor such as hemorrhage, brain injury sepsis, pulmonary embolism or severe chronic obstructive pulmonary disease (COPD).<ref name="Akashi2015" />
It occurs more commonly in postmenopausal women.<ref name="Akashi2015" />
==Signs and symptoms== The typical presentation of takotsubo cardiomyopathy is chest pain with or without shortness of breath and associated electrocardiogram (ECG) changes mimicking an anterior wall myocardial infarction. During the course of evaluation of the patient, a bulging out of the left ventricular apex with a hypercontractile base of the left ventricle is often noted. It is the hallmark bulging-out of the apex of the heart with preserved function of the base that earned the syndrome the name ''takotsubo'' ("octopus trap") in Japan, where it was first described.<ref name="Gianni">{{cite journal | vauthors = Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E | title = Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review | journal = European Heart Journal | volume = 27 | issue = 13 | pages = 1523–1529 | date = July 2006 | pmid = 16720686 | doi = 10.1093/eurheartj/ehl032 | doi-access = free }}</ref>
Stress is the main factor in takotsubo cardiomyopathy, with more than 85% of cases set in motion by either a physically or emotionally stressful event that prefaces the start of symptoms.<ref name="circ.ahajournals.org">{{cite journal | vauthors = Sharkey SW, Lesser JR, Maron BJ | title = Cardiology Patient Page. Takotsubo (stress) cardiomyopathy | journal = Circulation | volume = 124 | issue = 18 | pages = e460–e462 | date = November 2011 | pmid = 22042929 | doi = 10.1161/CIRCULATIONAHA.111.052662 | publisher = American Heart Association | doi-access = free }}</ref> Acute asthma, surgery, subarachnoid hemorrhage, chemotherapy, and stroke are examples of physical stressors.<ref name="circ.ahajournals.org"/> In a few cases, the stress may be a happy event.<ref>{{cite magazine| vauthors = Coghlan A |title=Shock of good news can hurt your heart as much as grief|journal=New Scientist|date=12 March 2016|url=https://www.newscientist.com/article/2079842}}</ref><ref>{{cite journal | vauthors = Ghadri JR, Sarcon A, Diekmann J, Bataiosu DR, Cammann VL, Jurisic S, Napp LC, Jaguszewski M, Scherff F, Brugger P, Jäncke L, Seifert B, Bax JJ, Ruschitzka F, Lüscher TF, Templin C | title = Happy heart syndrome: role of positive emotional stress in takotsubo syndrome | journal = European Heart Journal | volume = 37 | issue = 37 | pages = 2823–2829 | date = October 2016 | pmid = 26935270 | pmc = 5841222 | doi = 10.1093/eurheartj/ehv757 }}</ref>
== Risk factors == === Stress trigger === Although there have been documented cases of TTS without a triggering stressor, it is widely recognized that TTS is preceded by a stressful or emotional event.<ref name="Pelliccia2017" /> Case series looking at large groups of patients report that some patients develop takotsubo cardiomyopathy after experiencing emotional stress. Some patients have a preceding clinical stressor (such as a brain injury, asthma attack or exacerbation of a chronic illness) and research has indicated that this type of stress may even occur more often than emotionally stressful triggers.<ref name="Templin_2015" /> Roughly one-third of patients have no preceding stressful event.<ref name="Elesber 2007 448–52">{{cite journal | vauthors = Elesber AA, Prasad A, Lennon RJ, Wright RS, Lerman A, Rihal CS | title = Four-year recurrence rate and prognosis of the apical ballooning syndrome | journal = Journal of the American College of Cardiology | volume = 50 | issue = 5 | pages = 448–452 | date = July 2007 | pmid = 17662398 | doi = 10.1016/j.jacc.2007.03.050 | doi-access = }}</ref> A 2009 large case series from Europe found that takotsubo cardiomyopathy was slightly more frequent during the winter season. This may be related to two possible/suspected pathophysiological causes: coronary spasms of microvessels, which are more prevalent in cold weather, and viral infections – such as Parvovirus B19 – which occur more frequently during the winter.<ref name="pmid18599137" />
=== Gender === Postmenopausal women are at greatest risk of developing TTS.<ref name="Pelliccia2017" /> This has led some researchers to theorize about the possible protective effects of estrogen in preventing TTS.<ref name="Komamura_2014">{{cite journal | vauthors = Komamura K, Fukui M, Iwasaku T, Hirotani S, Masuyama T | title = Takotsubo cardiomyopathy: Pathophysiology, diagnosis and treatment | journal = World Journal of Cardiology | volume = 6 | issue = 7 | pages = 602–609 | date = July 2014 | pmid = 25068020 | pmc = 4110608 | doi = 10.4330/wjc.v6.i7.602 | doi-access = free }}</ref><ref name="Ghadri_2018" />
=== Genetic risk factors === {{as of|2014}} it is being investigated whether certain genetic traits associated with catecholamine receptors found on cardiac muscle cells play a role in the development of TTS.<ref name="Komamura_2014" /> There is limited evidence tying TTS directly to a specific genetic expression or mutation, however there is a widely held hypothesis supporting the idea of the interaction between environmental factors and the interplay of genetic predisposition leading to the susceptibility to microvascular alterations that contribute to the TTS disease process.<ref name="Ghadri_2018" />
=== Hormonal dysregulation === Certain endocrine diseases including pheochromocytoma and thyrotoxicosis have been identified as potential risk factors for TTS.<ref>{{cite journal | vauthors = Y-Hassan S, Falhammar H | title = Cardiovascular Manifestations and Complications of Pheochromocytomas and Paragangliomas | journal = Journal of Clinical Medicine | volume = 9 | issue = 8 | page = 2435 | date = July 2020 | pmid = 32751501 | pmc = 7465968 | doi = 10.3390/jcm9082435 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kalra S, Lakhani OJ, Chaudhary S | title = Takotsubo Endocrinopathy | journal = European Endocrinology | volume = 16 | issue = 2 | pages = 97–99 | date = October 2020 | pmid = 33117439 | pmc = 7572168 | doi = 10.17925/EE.2020.16.2.97 }}</ref> The relationship between thyroid function and stress cardiomyopathy is marked by a dual phenotype, where both impending primary hyperthyroidism and a high set point of thyroid homeostasis (encoding type 2 allostatic load) are common phenomena.<ref name="Aweimer_2020">{{cite journal | vauthors = Aweimer A, El-Battrawy I, Akin I, Borggrefe M, Mügge A, Patsalis PC, Urban A, Kummer M, Vasileva S, Stachon A, Hering S, Dietrich JW | title = Abnormal thyroid function is common in takotsubo syndrome and depends on two distinct mechanisms: results of a multicentre observational study | journal = Journal of Internal Medicine | volume = 289 | issue = 5 | pages = 675–687 | date = May 2021 | pmid = 33179374 | doi = 10.1111/joim.13189 | doi-access = free }}</ref> A multi-centre observation study found normal thyroid function to be the exception rather than the rule in TTS.<ref name="Aweimer_2020"/> Especially hyperthyroidism is highly prevalent in takotsubo cardiomyopathy, and it seems to predict a poor prognosis in terms of complications and mortality.<ref>{{cite journal | vauthors = Scudiero F, Arcari L, Silverio A, Citro R, Bossone E, Autore C, Muraca I, Chinati P, Sanna G, Piti A, Parodi G |title=Hyperthyroidism in Takotsubo syndrome: prevalence, clinical features and long-term outcomes |journal=European Heart Journal |date=25 November 2020 |volume=41 |issue=Supplement_2 |article-number=ehaa946.1812 |doi=10.1093/ehjci/ehaa946.1812|doi-access=free }}</ref> This observation was confirmed by results of the international GEIST registry, which demonstrated that thyrotoxicosis is associated with significantly increased fatality, whereas hypothyroidism indicates a better survival.<ref name="Aweimer_2024">{{cite journal | vauthors = Aweimer A, Dietrich JW, Santoro F, Fàbregas MC, Mügge A, Núñez-Gil IJ, Vazirani R, Vedia O, Pätz T, Ragnatela I, Arcari L, Volpe M, Corbì-Pascual M, Martinez-Selles M, Almendro-Delia M, Sionis A, Uribarri A, Thiele H, Brunetti ND, Eitel I, Stiermaier T, Hamdani N, Abumayyaleh M, Akin I, El-Battrawy I | title = Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registry | journal = eBioMedicine | volume = 102 | article-number = 105063 | date = April 2024 | pmid = 38502972 | pmc = 10963195 | doi = 10.1016/j.ebiom.2024.105063 }}</ref>
==Pathophysiology== The cause of takotsubo cardiomyopathy is not fully understood, but several mechanisms have been proposed.<ref>{{cite journal | vauthors = Veillet-Chowdhury M, Hassan SF, Stergiopoulos K | title = Takotsubo cardiomyopathy: a review | journal = Acute Cardiac Care | volume = 16 | issue = 1 | pages = 15–22 | date = March 2014 | pmid = 24552225 | doi = 10.3109/17482941.2013.869346 | s2cid = 8577417 }}</ref> It is well documented that elevated catecholamine levels have been implicated in the vast majority of TTS cases. Theories suggest a link between brain activation of stress-related biochemicals (including neuropeptides) and the effects these chemicals have on areas of the heart, especially neuropeptide Y.<ref>{{cite journal | vauthors = Medina de Chazal H, Del Buono MG, Keyser-Marcus L, Ma L, Moeller FG, Berrocal D, Abbate A | title = Stress Cardiomyopathy Diagnosis and Treatment: JACC State-of-the-Art Review | journal = Journal of the American College of Cardiology | volume = 72 | issue = 16 | pages = 1955–1971 | date = October 2018 | pmid = 30309474 | pmc = 7058348 | doi = 10.1016/j.jacc.2018.07.072 }}</ref> Specifically, adrenal stimulation by the sympathetic nervous system has been seen in cases ranging from physical events such as ischemic stroke, to emotional events such as depression or loss of a loved-one.<ref>{{cite journal | vauthors = Redfors B, Shao Y, Omerovic E | title = Stress-induced cardiomyopathy (Takotsubo)--broken heart and mind? | journal = Vascular Health and Risk Management | volume = 9 | pages = 149–154 | date = 2013 | pmid = 23626469 | pmc = 3632585 | doi = 10.2147/VHRM.S40163 | doi-access = free }}</ref> How these increased levels of catecholamines act in the body to produce the changes seen with TTS is not clearly understood.<ref name="Ghadri_2018" /><ref name="Akashi2015" /><ref name="Pelliccia2017" /><ref name="Komamura_2014" /> Research supports the widely-held theory that microvascular dysfunction and coronary vasospasm caused by a rapid influx of catecholamines to cardiac myocytes, results in apical stunning and transient cardiomyopathy.<ref name="Ghadri_2018" /><ref name="Akashi2015" /><ref name="Pelliccia2017" />
# '''Microvascular dysfunction/Transient vasospasm:''' Some of the original researchers of takotsubo suggested that multiple simultaneous spasms of coronary arteries could cause enough loss of blood flow to cause transient stunning of the myocardium.<ref>{{cite journal | vauthors = Kurisu S, Sato H, Kawagoe T, Ishihara M, Shimatani Y, Nishioka K, Kono Y, Umemura T, Nakamura S | title = Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction | journal = American Heart Journal | volume = 143 | issue = 3 | pages = 448–455 | date = March 2002 | pmid = 11868050 | doi = 10.1067/mhj.2002.120403 }}</ref> Other researchers have shown that vasospasm is much less common than earlier thought.<ref name="Tsuchuhashi K et al. JACC 2001">{{cite journal | vauthors = 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 | title = Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris-Myocardial Infarction Investigations in Japan | journal = Journal of the American College of Cardiology | volume = 38 | issue = 1 | pages = 11–18 | date = July 2001 | pmid = 11451258 | doi = 10.1016/S0735-1097(01)01316-X | doi-access = }}</ref><ref name="Kawai et al. JPJ 2000">Kawai et al. JPJ 2000.</ref><ref name="Desmet et al. Heart 2003">{{cite journal | vauthors = Desmet WJ, Adriaenssens BF, Dens JA | title = Apical ballooning of the left ventricle: first series in white patients | journal = Heart | volume = 89 | issue = 9 | pages = 1027–1031 | date = September 2003 | pmid = 12923018 | pmc = 1767823 | doi = 10.1136/heart.89.9.1027 }}</ref> It has been observed that vasospasms, even in multiple arteries, do not correlate with the areas of myocardium that are not contracting.<ref>{{cite journal | vauthors = Abe Y, Kondo M, Matsuoka R, Araki M, Dohyama K, Tanio H | title = Assessment of clinical features in transient left ventricular apical ballooning | journal = Journal of the American College of Cardiology | volume = 41 | issue = 5 | pages = 737–742 | date = March 2003 | pmid = 12628715 | doi = 10.1016/S0735-1097(02)02925-X | doi-access = free }}</ref> However, coronary artery vasospasm is still believed to contribute to the TTS disease process. The theory of vasospasm is not easily distinguished from microvascular dysfunction, and microvascular dysfunction could explain vasospasticity.<ref name="Pelliccia2017" /> Impaired microvascular function is seen in a vast majority, if not all, of patients with TTS and is one of the most widely held theories.<ref name="Ghadri_2018" /><ref name="Komamura_2014" /> Most of the dysfunction occurs from abnormalities within the endothelial linings of blood vessels supplying the heart.<ref name="Komamura_2014" /> In TTS, these highly sensitive interior linings of the vessels have reduced functionality which create dysregulation of vascular tone and predispose the individual to vasoconstriction. When the increased vasoconstriction from catecholamines occurs, the result is acute cardiac ischemia.<ref name="Ghadri_2018" /><ref name="Pelliccia2017" /><ref name="Komamura_2014" /> # '''Catecholamine-induced myocyte injury:''' It has been suggested that the response to catecholamines (such as epinephrine and norepinephrine, released in response to stress) leads to heart muscle dysfunction that contributes to takotsubo cardiomyopathy.<ref name="Pelliccia2017" /> The effects of this toxicity can be greater in those with a predisposition to anxiety or panic disorders.<ref name="Akashi2015" /> Delivery of catecholamines (epinephrine, norepinephrine) via circulating blood and through direct delivery from cardiac nerves is increased by the stimulation of stress control centers of the brain.<ref name="Akashi2015" /> During an emotionally or physically stressful event, brain centers initiate the sympathetic nervous pathways and increase myocardial activity. Excessive catecholamine stimulation has a toxic effect on cardiac muscle cells which creates necrosis of the contractile units of cells similarly seen during acute myocardial infarction.<ref name="Ghadri_2018" /><ref name="Pelliccia2017" /> The increased workload of cardiac muscle created by the stimulation of catecholamines, increases the need for more blood and oxygen to these muscles to sustain function. When these demands are unable to be met, the heart is starved of blood and oxygen and begins to die.<ref name="Akashi2015" /> Included in the cytotoxic sequela of catecholamine toxicity is the molecular transformation of the cardiac myocyte to produce apical stunning. # '''Mid-ventricular and left ventricular outflow obstruction:''' It has been suggested that a mid-ventricular wall thickening with outflow obstruction is important in the pathophysiology.<ref>{{cite journal | vauthors = Merli E, Sutcliffe S, Gori M, Sutherland GG | title = Tako-Tsubo cardiomyopathy: new insights into the possible underlying pathophysiology | journal = European Journal of Echocardiography | volume = 7 | issue = 1 | pages = 53–61 | date = January 2006 | pmid = 16182610 | doi = 10.1016/j.euje.2005.08.003 | doi-access = free }}</ref> A quarter of unselected patients with TTS who presented to an emergency department were found to have obstructive hypertrophic cardiomyopathy (HCM) on blinded echocardiographic analysis.<ref>{{cite journal | vauthors = Sherrid MV, Riedy K, Rosenzweig B, Massera D, Saric M, Swistel DG, Ahluwalia M, Arabadjian M, DeFonte M, Stepanovic A, Serrato S, Xia Y, Zhong H, Maron MS, Maron BJ, Reynolds HR | title = Distinctive Hypertrophic Cardiomyopathy Anatomy and Obstructive Physiology in Patients Admitted With Takotsubo Syndrome | language = English | journal = The American Journal of Cardiology | volume = 125 | issue = 11 | pages = 1700–1709 | date = June 2020 | pmid = 32278461 | doi = 10.1016/j.amjcard.2020.02.013 }}</ref> These patients had septal thickening, systolic anterior motion (SAM) of the mitral valve, left ventricular outflow tract (LVOT) obstruction with mean peak outflow gradients of 71 ±40mmHg. Compared with normal controls, the patients with SAM had longer anterior mitral leaflets, thicker septum (16 ±4 mm), and anterior displacement of the mitral valve in LV cavity. Moreover, in the patients with SAM, distinctive characteristics of HCM, including the mitral valve abnormalities persisted after normalization of LV function. It had previously been hypothesized that LVOT obstruction was due to a geometric shape-change of the LV caused by ballooning. In contrast, this data and others indicate that SAM and the outflow obstruction, rather are the cause of the LV ballooning in these patients. Patients with obstructive HCM may develop acute LV ballooning that resembles TTS when latent obstruction becomes severe and unrelenting.<ref name="Sherrid_2011">{{cite journal | vauthors = Sherrid MV, Balaran SK, Korzeniecki E, Chaudhry FA, Swistel DG | title = Reversal of acute systolic dysfunction and cardiogenic shock in hypertrophic cardiomyopathy by surgical relief of obstruction | journal = Echocardiography | volume = 28 | issue = 9 | pages = E174–E179 | date = October 2011 | pmid = 21801200 | doi = 10.1111/j.1540-8175.2011.01459.x }}</ref><ref name="Sherrid_2021">{{cite journal | vauthors = Sherrid MV, Swistel DG, Olivotto I, Pieroni M, Wever-Pinzon O, Riedy K, Bach RG, Husaini M, Cresci S, Reyentovich A, Massera D, Maron MS, Maron BJ, Kim B | title = Syndrome of Reversible Cardiogenic Shock and Left Ventricular Ballooning in Obstructive Hypertrophic Cardiomyopathy | journal = Journal of the American Heart Association | volume = 10 | issue = 20 | article-number = e021141 | date = October 2021 | pmid = 34634917 | pmc = 8751867 | doi = 10.1161/JAHA.121.021141 }}</ref><ref>{{cite journal | vauthors = Singh A, Razzouk L, Massera D, Sherrid MV | title = Acute Left Ventricular Ballooning: Tools to Differentiate Hypertrophic Cardiomyopathy with Outflow Obstruction from Neurohumoral Takotsubo Syndrome | journal = Reviews in Cardiovascular Medicine | volume = 24 | issue = 5 | article-number = 154 | date = May 2023 | pmid = 39076741 | pmc = 11273027 | doi = 10.31083/j.rcm2405154 }}</ref><ref>{{cite journal | vauthors = Citro R, Bellino M, Merli E, Di Vece D, Sherrid MV | title = Obstructive Hypertrophic Cardiomyopathy and Takotsubo Syndrome: How to Deal With Left Ventricular Ballooning? | journal = Journal of the American Heart Association | volume = 12 | issue = 21 | article-number = e032028 | date = November 2023 | pmid = 37889174 | pmc = 10727392 | doi = 10.1161/JAHA.123.032028 }}</ref> This observation has supplemented previous reports that acute LV ballooning punctuated the course of 1% of obstructive HCM patients, occurring even in recent clinical trials of pharmacologic agents.<ref>{{cite journal | vauthors = Sherrid MV, Riedy K, Rosenzweig B, Ahluwalia M, Arabadjian M, Saric M, Balaram S, Swistel DG, Reynolds HR, Kim B | title = Hypertrophic cardiomyopathy with dynamic obstruction and high left ventricular outflow gradients associated with paradoxical apical ballooning | journal = Echocardiography | volume = 36 | issue = 1 | pages = 47–60 | date = January 2019 | pmid = 30548699 | doi = 10.1111/echo.14212 }}</ref><ref>{{cite journal | vauthors = Olivotto I, Oreziak A, Barriales-Villa R, Abraham TP, Masri A, Garcia-Pavia P, Saberi S, Lakdawala NK, Wheeler MT, Owens A, Kubanek M, Wojakowski W, Jensen MK, Gimeno-Blanes J, Afshar K, Myers J, Hegde SM, Solomon SD, Sehnert AJ, Zhang D, Li W, Bhattacharya M, Edelberg JM, Waldman CB, Lester SJ, Wang A, Ho CY, Jacoby D | title = Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial | language = English | journal = Lancet | volume = 396 | issue = 10253 | pages = 759–769 | date = September 2020 | pmid = 32871100 | doi = 10.1016/S0140-6736(20)31792-X | hdl = 2158/1209303 | hdl-access = free }}</ref> The cause is afterload mismatch and supply-demand ischemia that frequently cause striking cardiographic abnormalities when LVOT gradients are more than 60 mmHg.<ref>{{cite journal | vauthors = Ormerod JO, Frenneaux MP, Sherrid MV | title = Myocardial energy depletion and dynamic systolic dysfunction in hypertrophic cardiomyopathy | journal = Nature Reviews. Cardiology | volume = 13 | issue = 11 | pages = 677–687 | date = November 2016 | pmid = 27411403 | doi = 10.1038/nrcardio.2016.98 }}</ref><ref>{{cite journal | vauthors = Barac I, Upadya S, Pilchik R, Winson G, Passick M, Chaudhry FA, Sherrid MV | title = Effect of obstruction on longitudinal left ventricular shortening in hypertrophic cardiomyopathy | journal = Journal of the American College of Cardiology | volume = 49 | issue = 11 | pages = 1203–1211 | date = March 2007 | pmid = 17367665 | doi = 10.1016/j.jacc.2006.10.070 }}</ref> Contributing to ischemia are intramural coronary narrowings in HCM due to intimal and medial hyperplasia of the arterioles.<ref>{{cite journal | vauthors = Maron BJ, Wolfson JK, Epstein SE, Roberts WC | title = Intramural ("small vessel") coronary artery disease in hypertrophic cardiomyopathy | journal = Journal of the American College of Cardiology | volume = 8 | issue = 3 | pages = 545–557 | date = September 1986 | pmid = 3745699 | doi = 10.1016/S0735-1097(86)80181-4 }}</ref><ref>{{cite journal | vauthors = Hughes RK, Augusto JB, Knott K, Davies R, Shiwani H, Seraphim A, Malcolmson JW, Khoury S, Joy G, Mohiddin S, Lopes LR, McKenna WJ, Kellman P, Xue H, Tome M, Sharma S, Captur G, Moon JC | title = Apical Ischemia Is a Universal Feature of Apical Hypertrophic Cardiomyopathy | journal = Circulation: Cardiovascular Imaging | volume = 16 | issue = 3 | article-number = e014907 | date = March 2023 | pmid = 36943913 | pmc = 10026964 | doi = 10.1161/CIRCIMAGING.122.014907 }}</ref> Acute LV ballooning due to SAM and LVOT obstruction can cause cardiogenic shock.<ref name="Sherrid_2011" /><ref name="Sherrid_2021" /> This complication may be severe enough to require mechanical LV support.<ref name="Sherrid_2021" /> If cardiogenic shock is refractory, with acidosis and oliguria, it may require surgical relief of LVOT obstruction. Strikingly, after outflow obstruction is relieved, LV function and hemodynamics return to normal within hours.<ref name="Sherrid_2011" /><ref name="Sherrid_2021" /> This is compelling evidence that the HCM and LVOT obstruction was the cause of the acute LV ballooning. There may be different phenocopies of TTS. Individual cases, though appearing similar, may have different pathophysiology.<ref>{{cite journal | vauthors = Pelliccia F, Kaski JC, Camici PG | title = Takotsubo syndrome's pathophysiology: still a mystery? | journal = European Heart Journal | volume = 40 | issue = 24 | page = 1989 | date = June 2019 | pmid = 30903135 | doi = 10.1093/eurheartj/ehz083 }}</ref><ref>{{cite journal | vauthors = Pelliccia F, Kaski JC, Crea F, Camici PG | title = Pathophysiology of Takotsubo Syndrome | journal = Circulation | volume = 135 | issue = 24 | pages = 2426–2441 | date = June 2017 | pmid = 28606950 | doi = 10.1161/CIRCULATIONAHA.116.027121 | url = http://openaccess.sgul.ac.uk/108780/3/FIGURES_%20the%20pathophysiology%20of%20Takotsubo%20Syndrome.pdf }}</ref> The most common cause is thought to be a direct adverse effect on the cardiomyocytes and microvasculature that may be conceptualized as neurohumoral TTS. Another, occurring in a minority of TTS patients, is caused by acute LVOT obstruction with distinctive features of HCM. Both may be precipitated by acute emotional stress. # '''Apical stunning:''' This stunning is largely seen as a protective effect produced by the flood of excess catecholamines into the cardiac muscle cell.<ref name="Pelliccia2017" /> Overstimulation of catecholamine receptors create physiological changes in the receptor which has an inverse effect on cardiac cellular function. Termed 'cellular-trafficking', this property of the cardiac muscle cell is actually a molecular transformation of the cell to produce a down-regulation of catecolaminergic sensitivity.<ref name="Akashi2015" /> This means that in the presence of excess epinephrine, a normal cardiac contraction is inhibited in an effort to reduce energy demands, prevent hyperactivity and spare the integrity of the cell.<ref name="Akashi2015" /><ref name="Pelliccia2017" /> Further bolstering this idea is the concentration of these kinds of receptors in the heart. Higher concentrations of the receptor effected to produce cardiac stunning are found closer to the apex of the ventricle. This is what creates the classic ballooning effect of the ventricle.<ref name="Akashi2015" /><ref name="Pelliccia2017" />
It is likely that there are multiple factors at play that could include some amount of vasospasm and failure of the microvasculature. These factors can overlap and create the complex sequela leading to ischemia and left ventricle contraction abnormality.<ref name="Pelliccia2017"/> For instance, estrogen, which confers protection to women by improving blood flow to heart muscle, is one biochemical pathway implicated in the TTS disease process. Once this protective mechanism is reduced through the decreased production of estrogen after menopause, there is thought to be an increase in endothelial dysfunction predisposing an individual to vasoconstriction and cardiac ischemia.<ref name="Akashi2015" /> An inciting stressful event elicits the release of catecholamines into the blood stream to create increased heart muscle activity and metabolism. This leads to further cardiac microvascular endothelial dysfunction through oxidative stress, alteration of ion-mediated channels, and electrolyte disturbances which ultimately alter myocardial cell membrane permeability and dysfunction.<ref name="Ghadri_2018" /><ref name="Pelliccia2017" /> Coupled with direct heart muscle toxicity, this crescendo of factors are implicated in the ballooning and heart failure characteristically seen in TTS.<ref name="Ghadri_2018" /><ref name="Akashi2015" /><ref name="Pelliccia2017" /><ref name="Komamura_2014" />
A 2019 case involved a 60-year-old woman presenting with TTS due to over-consumption of wasabi, mistaking it for avocado.<ref name="was">{{cite journal | vauthors = Finkel-Oron A, Olchowski J, Jotkowitz A, Barski L | title = Takotsubo cardiomyopathy triggered by wasabi consumption: can sushi break your heart? | journal = BMJ Case Reports | volume = 12 | issue = 9 | article-number = e230065 | date = September 2019 | pmid = 31540920 | pmc = 6768342 | doi = 10.1136/bcr-2019-230065 }}</ref>
==Diagnosis== Several well regarded institutions of medical research have produced clinical criteria useful in diagnosing TTS. One of the first sets of guidelines was initially published in 2004 and again in 2008 by the Mayo Clinic. Other research institutions proposing diagnostic criteria include the Japanese Takotsubo Cardiomyopathy Study Group, University of Gothenburg, Johns Hopkins University, the Takotsubo Italian Network and the Heart Failure Associates TTS Taskforce of the European Society of Cardiology.<ref name="Redfors_2014">{{cite journal | vauthors = Redfors B, Shao Y, Lyon AR, Omerovic E | title = Diagnostic criteria for takotsubo syndrome: a call for consensus | journal = International Journal of Cardiology | volume = 176 | issue = 1 | pages = 274–276 | date = September 2014 | pmid = 25043217 | doi = 10.1016/j.ijcard.2014.06.094 }}</ref> All of the research institutions agree on at least two main criteria needed to accurately diagnose TTS: 1) transient left ventricular wall motion abnormality and 2) the absence of a condition obviously explaining this wall motion abnormality (coronary artery lesion, hypoperfusion, myocarditis, toxicity, etc.). Other commonly acknowledged criteria necessary for diagnosis include characteristic EKG changes and mild to modest elevation in cardiac troponin.<ref name="Redfors_2014" />
Transient apical ballooning syndrome or takotsubo cardiomyopathy is found in 1.7–2.2% of patients presenting with acute coronary syndrome.<ref name="pmid18599137" /> While the original case studies reported on individuals in Japan, takotsubo cardiomyopathy has been noted more recently in the United States and Western Europe. It is likely that the syndrome previously went undiagnosed before it was described in detail in the Japanese literature. Evaluation of individuals with takotsubo cardiomyopathy typically includes a coronary angiogram to rule out occlusion of the left anterior descending artery, which will not reveal any significant blockages that would cause the left ventricular dysfunction. Provided that the individual survives their initial presentation, the left ventricular function improves within two months.{{citation needed|date=February 2021}}
The diagnosis of takotsubo cardiomyopathy may be difficult upon presentation. The ECG findings often are confused with those found during an acute anterior wall myocardial infarction.<ref name="Azzarelli-2006">{{cite journal | vauthors = Azzarelli S, Galassi AR, Amico F, Giacoppo M, Argentino V, Tomasello SD, Tamburino C, Fiscella A | title = Clinical features of transient left ventricular apical ballooning | journal = The American Journal of Cardiology | volume = 98 | issue = 9 | pages = 1273–1276 | date = November 2006 | pmid = 17056345 | doi = 10.1016/j.amjcard.2006.05.065 }}</ref><ref name=Bybee-2006>{{cite journal | vauthors = Bybee KA, Motiei A, Syed IS, Kara T, Prasad A, Lennon RJ, Murphy JG, Hammill SC, Rihal CS, Wright RS | title = Electrocardiography cannot reliably differentiate transient left ventricular apical ballooning syndrome from anterior ST-segment elevation myocardial infarction | journal = Journal of Electrocardiology | volume = 40 | issue = 1 | pages = 38.e1–38.e6 | date = January 2007 | pmid = 17067626 | doi = 10.1016/j.jelectrocard.2006.04.007 }}</ref> It classically mimics ST-segment elevation myocardial infarction, and is characterised by acute onset of transient ventricular apical wall motion abnormalities (ballooning) accompanied by chest pain, shortness of breath, ST-segment elevation, T-wave inversion or QT-interval prolongation on ECG. Cardiac enzymes are usually negative and are moderate at worst, and cardiac catheterization usually shows absence of significant coronary artery disease.<ref name="pmid18599137"/>
The diagnosis is made by the pathognomonic wall motion abnormalities, in which the base of the left ventricle is contracting normally or is hyperkinetic while the remainder of the left ventricle is akinetic or dyskinetic. This is accompanied by the lack of significant coronary artery disease that would explain the wall motion abnormalities. Although apical ballooning has been described classically as the angiographic manifestation of takotsubo, it has been shown that left ventricular dysfunction in this syndrome includes not only the classic apical ballooning, but also different angiographic morphologies such as mid-ventricular ballooning and, rarely, local ballooning of other segments.<ref name="pmid18599137"/><ref name="pmid17651841">{{cite journal | vauthors = Pilgrim TM, Wyss TR | title = Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: A systematic review | journal = International Journal of Cardiology | volume = 124 | issue = 3 | pages = 283–292 | date = March 2008 | pmid = 17651841 | doi = 10.1016/j.ijcard.2007.07.002 }}</ref><ref name="pmid16948453">{{cite journal | vauthors = Shimizu M, Kato Y, Masai H, Shima T, Miwa Y | title = [Recurrent episodes of takotsubo-like transient left ventricular ballooning occurring in different regions: a case report] | journal = Journal of Cardiology | volume = 48 | issue = 2 | pages = 101–107 | date = August 2006 | pmid = 16948453 }}</ref><ref name="pmid16875987">{{cite journal | vauthors = Hurst RT, Askew JW, Reuss CS, Lee RW, Sweeney JP, Fortuin FD, Oh JK, Tajik AJ | title = Transient midventricular ballooning syndrome: a new variant | journal = Journal of the American College of Cardiology | volume = 48 | issue = 3 | pages = 579–583 | date = August 2006 | pmid = 16875987 | doi = 10.1016/j.jacc.2006.06.015 | doi-access = }}</ref><ref name="pmid15996774">{{cite journal | vauthors = Yasu T, Tone K, Kubo N, Saito M | title = Transient mid-ventricular ballooning cardiomyopathy: a new entity of Takotsubo cardiomyopathy | journal = International Journal of Cardiology | volume = 110 | issue = 1 | pages = 100–101 | date = June 2006 | pmid = 15996774 | doi = 10.1016/j.ijcard.2005.05.060 }}</ref>
The ballooning patterns were classified by Shimizu et al. as ''takotsubo type'' for apical akinesia and basal hyperkinesia, ''reverse takotsubo'' for basal akinesia and apical hyperkinesia, ''mid-ventricular type'' for mid-ventricular ballooning accompanied by basal and apical hyperkinesia, and ''localised type'' for any other segmental left ventricular ballooning with clinical characteristics of takotsubo-like left ventricular dysfunction.<ref name="pmid16948453"/>
In short, the main criteria for the diagnosis of takotsubo cardiomyopathy are: the patient must have experienced a stressor before the symptoms began to arise; the patient's ECG reading must show abnormalities from a normal heart; the patient must not show signs of coronary blockage or other common causes of heart troubles; the levels of cardiac enzymes in the heart must be elevated or irregular; and the patient must recover complete contraction and be functioning normally in a short amount of time.<ref>{{cite journal | vauthors = Golabchi A, Sarrafzadegan N | title = Takotsubo cardiomyopathy or broken heart syndrome: A review article | journal = Journal of Research in Medical Sciences | volume = 16 | issue = 3 | pages = 340–345 | date = March 2011 | pmid = 22091255 | pmc = 3214344 }}</ref>
<gallery> File:Takotsubo ventriculography.gif|Left ventriculography during systole showing apical ballooning akinesis with basal hyperkinesis in a characteristic takotsubo ventricle File:Takotsubo left ventriculogram.jpg|Left ventriculogram during systole displaying the characteristic apical ballooning with apical motionlessness in a patient with takotsubo cardiomyopathy File:Takotsubo ultrasound.gif|(A) Echocardiogram showing dilatation of the left ventricle in the acute phase (B) Resolution of left ventricular function on repeat echocardiogram six days later File:Takotsubo ECG.JPEG|ECG showing sinus tachycardia and non-specific ST and T wave changes from a person with confirmed takotsubo cardiomyopathy File:UOTW 74 - Ultrasound of the Week 2.webm|Echocardiogram showing the effects of the disease<ref>{{cite web|title=UOTW No. 74 - Ultrasound of the Week|url=https://www.ultrasoundoftheweek.com/uotw-74/|website=Ultrasound of the Week|access-date=27 May 2017|date=20 September 2016}}</ref> </gallery>
==Treatment== The treatment of takotsubo cardiomyopathy is generally supportive in nature, for it is considered a transient disorder.<ref name="McPhee_2016">{{Cite book|title=Current medical diagnosis & treatment 2017 |isbn=978-1-259-58511-1|edition=Fifty-sixth|location=New York | publisher = McGraw Hill Education |oclc=957316517| vauthors = McPhee SJ, Rabow MW, Papadakis MA |date=1 September 2016}}</ref> Treatment is dependent on whether patients experience heart failure or acute hypotension and shock. In many individuals, left ventricular function normalizes within two months.<ref name="Akashi-2003">{{cite journal | vauthors = Akashi YJ, Nakazawa K, Sakakibara M, Miyake F, Koike H, Sasaka K | title = The clinical features of takotsubo cardiomyopathy | journal = QJM | volume = 96 | issue = 8 | pages = 563–573 | date = August 2003 | pmid = 12897341 | doi = 10.1093/qjmed/hcg096 | doi-access = }}</ref><ref name="Nyui-2000">{{cite journal | vauthors = Nyui N, Yamanaka O, Nakayama R, Sawano M, Kawai S | title = 'Tako-Tsubo' transient ventricular dysfunction: a case report | journal = Japanese Circulation Journal | volume = 64 | issue = 9 | pages = 715–719 | date = September 2000 | pmid = 10981859 | doi = 10.1253/jcj.64.715 | doi-access = free }}</ref> Aspirin and other heart drugs also appear to help in the treatment of this disease, even in extreme cases.<ref>{{Cite news|url=https://news.bbc.co.uk/1/hi/health/7967660.stm|work=BBC News |title=Medics 'can mend a broken heart'|language=en-GB|access-date=29 June 2017|date=27 March 2009}}</ref><ref name="Shah_2017">{{Cite book|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK430798/|title=StatPearls| vauthors = Shah S, Bhimji S |date=2017|publisher=StatPearls Publishing|location=Treasure Island (FL)|pmid=28613549|chapter=Cardiomyopathy, Takotsubo Syndrome (Transient Apical Ballooning, Stress-Induced Cardiomyopathy, Gebrochenes-Herz Syndrome)|url=https://www.ncbi.nlm.nih.gov/books/NBK430798/}}</ref> After the patient has been diagnosed, and myocardial infarction (heart attack) ruled out, the aspirin regimen may be discontinued, and treatment becomes that of support for the patient.<ref>{{cite journal | vauthors = Derrick D | title = The"broken heart syndrome": understanding Takotsubo cardiomyopathy | journal = Critical Care Nurse | volume = 29 | issue = 1 | pages = 49–57; quiz 58 | date = February 2009 | pmid = 19182280 | doi = 10.4037/ccn2009451 }}</ref>
While medical treatments are important to address the acute symptoms of takotsubo cardiomyopathy, further treatment includes lifestyle changes.<ref>{{cite web|url=http://www.nhlbi.nih.gov/health/health-topics/topics/broken-heart-syndrome/treatment|archive-url=https://web.archive.org/web/20141216064419/http://www.nhlbi.nih.gov/health/health-topics/topics/broken-heart-syndrome/treatment|archive-date=16 December 2014|title=Broken Heart Syndrome |publisher=National Heart, Lung, and Blood Institute|access-date=2 January 2018}}</ref> It is important that the individual stay physically healthy while learning and maintaining methods to manage stress, and to cope with future difficult situations.{{citation needed|date=February 2021}}
Although the symptoms of takotsubo cardiomyopathy usually go away on their own and the condition completely resolves itself within a few weeks, some serious short and long-term complications can happen that must be treated.<ref name=Kurisu2014>{{cite journal | vauthors = Kurisu S, Kihara Y | title = Clinical management of takotsubo cardiomyopathy | journal = Circulation Journal | volume = 78 | issue = 7 | pages = 1559–1566 | date = 2014 | pmid = 24964980 | doi = 10.1253/circj.cj-14-0382 | doi-access = free }}</ref> These most commonly include congestive heart failure and very low blood pressure, and less commonly include blood clotting in the apex of the left ventricle, irregular heart beat, and tearing of the heart wall.<ref name=Kurisu2014/>
===Heart failure=== For patients in acute heart failure, ACE inhibitors, angiotensin receptor blockers, and beta blockers, are considered mainstays of heart failure treatment. But use of beta blockers specifically for takotsubo cardiomyopathy is controversial, because they may confer no benefit.<ref name="McPhee_2016" />
===Low blood pressure=== For people with cardiogenic shock, medical treatment is based on whether a left ventricular outflow tract (LVOT) obstruction is present.<ref name="www.uptodate.com">{{Cite web|url=https://www.uptodate.com/contents/management-and-prognosis-of-stress-takotsubo-cardiomyopathy|title=Management and prognosis of stress (takotsubo) cardiomyopathy|website=www.uptodate.com|access-date=21 October 2017}}</ref> Therefore, early echocardiography is necessary to determine proper management. For those with obstructed LVOTs inotropic agents should not be used, but instead should be managed like patients with hypertrophic cardiomyopathy, (e.g. phenylephrine and fluid resuscitation).<ref name="McPhee_2016" /> For cases in which the LVOT is not obstructed, inotropic therapy (e.g. dobutamine and dopamine) may be used, but with the consideration that takotsubo is caused by excess catecholamines.<ref name="www.uptodate.com" />
Furthermore, mechanical circulatory support<ref>{{cite journal | vauthors = Mariani S, Richter J, Pappalardo F, Bělohlávek J, Lorusso R, Schmitto JD, Bauersachs J, Napp LC | title = Mechanical circulatory support for Takotsubo syndrome: a systematic review and meta-analysis | journal = International Journal of Cardiology | volume = 316 | pages = 31–39 | date = October 2020 | pmid = 32473281 | doi = 10.1016/j.ijcard.2020.05.033 | s2cid = 219156278 }}</ref> (MCS) with an intra-aortic balloon pump (IABP) is well-established as supportive treatment.<ref name="www.uptodate.com" /><ref>{{cite journal | vauthors = Akashi YJ, Goldstein DS, Barbaro G, Ueyama T | title = Takotsubo cardiomyopathy: a new form of acute, reversible heart failure | journal = Circulation | volume = 118 | issue = 25 | pages = 2754–2762 | date = December 2008 | pmid = 19106400 | pmc = 4893309 | doi = 10.1161/CIRCULATIONAHA.108.767012 }}</ref>
==Prognosis== Despite the grave initial presentation in some of the patients, most of the patients survive the initial acute event, with a very low rate of in-hospital mortality or complications. Once a patient has recovered from the acute stage of the syndrome, they can expect a favorable outcome and the long-term prognosis is excellent for most.<ref name="pmid18599137"/><ref name="Gianni" /><ref name="pmid17651841" /> Even when ventricular systolic function is heavily compromised at presentation, it typically improves within the first few days and normalises within the first few months.<ref name="pmid18599137"/><ref name="Tsuchuhashi K et al. JACC 2001"/><ref name="Kawai et al. JPJ 2000"/><ref name="Desmet et al. Heart 2003"/> Although infrequent, recurrence of the syndrome has been reported and seems to be associated with the nature of the trigger.<ref name="pmid18599137"/><ref name="Elesber 2007 448–52"/> While men experience TTS at much lower rates than women, they also experience much higher rates of complication, reoccurrence, and mortality; the cause of this sex difference is still unknown, but it is hypothesized that the social aspect of the doctor-patient interaction affects the way that physicians recognize and generate individual treatment plans for men compared to women.<ref>Weidner, K. J., El-Battrawy, I., Behnes, M., Schramm, K., Fastner, C., Kuschyk, J., Hoffmann, U., & Borggrefe, M. (2017). Therapeutics and Clinical Risk Management Dovepress sex differences of in-hospital outcome and long-term mortality in patients with Takotsubo cardiomyopathy. Therapeutics and Clinical Risk Management, 13–863. https://doi.org/10.2147/TCRM.S131760</ref> Stress cardiomyopathy is now a well-recognized cause of acute congestive heart failure, lethal abnormal heart rhythms, and rupture of the heart wall.<ref name="PMID19686084" />
==Epidemiology== Takotsubo syndrome represents about 2% of all patients (and 5–6% of all female patients) who are initially diagnosed with acute coronary syndrome (ACS).<ref name="Ghadri_2018" /><ref name="Awad 2018" /> It accounts for 0.02% of all hospitalizations in the US.<ref name="Ghadri_2018" /> About 90% of TTS patients are women,<ref name="Ghadri_2018" /><ref name="Awad 2018" /> whose mean age is about 68 years, and 80% of whom are older than 50 years.<ref name="Ghadri_2018" /> About 2.2% of TTS cases had the reversed (basal) variant.<ref name="Awad 2018">{{cite journal | vauthors = Awad HH, McNeal AR, Goyal H | title = Reverse Takotsubo cardiomyopathy: a comprehensive review | journal = Annals of Translational Medicine | volume = 6 | issue = 23 | page = 460 | date = December 2018 | pmid = 30603648 | pmc = 6312810 | doi = 10.21037/atm.2018.11.08 | publisher = AME Publishing Company | doi-access = free }}</ref> Recurrence rate of TTS is about 1.8% per-patient year.<ref name="Ghadri_2018" />
There is a steady annual increase in takotsubo cardiomyopathy among both women and men from 2006 to 2017, with the sharpest increases among women 50 and older.<ref>{{cite web |title='Broken heart syndrome' on the rise, increasingly among women |date=13 Oct 2021 |access-date=9 Feb 2022 |website=American Heart Association News | vauthors = Christensen T |url=https://www.heart.org/en/news/2021/10/13/broken-heart-syndrome-is-on-the-rise-especially-among-older-women}}</ref>
==History== thumb|The Japanese octopus traps after which this disease is named<ref name="PMID19686084"/> Rees, et al. wrote in 1967 that the death of a close relative increases the risk of dying within one year by a factor of seven.<ref>{{cite journal | vauthors = Rees WD, Lutkins SG | title = Mortality of bereavement | journal = British Medical Journal | volume = 4 | issue = 5570 | pages = 13–16 | date = October 1967 | pmid = 6047819 | pmc = 1748842 | doi = 10.1136/bmj.4.5570.13 }}</ref>
Engel wrote about sudden and rapid death during psychological stress in 1971 and itemized 8 causation categories: (1) on the impact of the collapse or death of a close person; (2) during acute grief; (3) on threat of loss of a close person; (4) during mourning or on an anniversary; (5) on loss of status or self-esteem; (6) personal danger or threat of injury; (7) after the danger is over; (8) reunion, triumph, or happy ending. He proposed these events provoke neurovegetative responses, involving both the flight-fight and conservation-withdrawal systems, conducive to lethal cardiac events, particularly in individuals with preexisting cardiovascular disease.<ref>{{cite journal | vauthors = Engel GL | title = Sudden and rapid death during psychological stress. Folklore or folk wisdom? | journal = Annals of Internal Medicine | volume = 74 | issue = 5 | pages = 771–782 | date = May 1971 | pmid = 5559442 | doi = 10.7326/0003-4819-74-5-771 }}</ref>
Although the first scientific description of takotsubo cardiomyopathy was not until the 1990s, Cebelin and Hirsch wrote about human stress cardiomyopathy in 1980. The two looked at homicidal assaults that had happened in Cuyahoga County, Ohio, the past 30 years, specifically those with autopsies who had no internal injury, but had died of physical assault. They found that 11 of 15 had myofibrillar degeneration similar to animal stress studies. In the end, they concluded their data supported "the theory of catecholamine mediation of these myocardial changes in man and of the lethal potential of stress through its effect on the heart".<ref>{{cite journal | vauthors = Cebelin MS, Hirsch CS | title = Human stress cardiomyopathy. Myocardial lesions in victims of homicidal assaults without internal injuries | journal = Human Pathology | volume = 11 | issue = 2 | pages = 123–132 | date = March 1980 | pmid = 7399504 | doi = 10.1016/s0046-8177(80)80129-8 }}</ref>
The syndrome was first named "takotsubo" by Japanese physician Hikaru Sato, who described "tako-tsubo-like left ventricular dysfunction" in a 1990 case study.<ref>{{Cite journal |last=Nagai |first=Michiaki |last2=Dote |first2=Keigo |last3=Ishihara |first3=Masaharu |last4=Kurisu |first4=Satoshi |date=2022-05-07 |title=In memoriam—Dr. Hikaru Sato: the discoverer of Takotsubo syndrome |url=https://academic.oup.com/eurheartj/article/43/18/1693/6551715 |journal=European Heart Journal |language=en |volume=43 |issue=18 |pages=1693–1696 |doi=10.1093/eurheartj/ehac146 |issn=0195-668X}}</ref> The name comes from the Japanese word ''takotsubo'' (蛸壷, "octopus trap"), because when affected by this condition, the left ventricle of the heart takes on a shape resembling the round jar used for catching lobsters and octopuses.<ref name="PMID19686084">{{cite journal | vauthors = Akashi YJ, Nef HM, Möllmann H, Ueyama T | title = Stress cardiomyopathy | journal = Annual Review of Medicine | volume = 61 | pages = 271–286 | year = 2010 | pmid = 19686084 | doi = 10.1146/annurev.med.041908.191750 }}</ref>
The syndrome reached international audiences through the media in 2005 when the ''New England Journal of Medicine'' wrote about the syndrome.<ref>{{cite journal | vauthors = Wittstein IS | title = The broken heart syndrome | journal = Cleveland Clinic Journal of Medicine | volume = 74 Suppl 1 | issue = 1 | pages = S17–S22 | date = February 2007 | pmid = 17455537 | doi = 10.3949/ccjm.74.Suppl_1.S17 | doi-broken-date = 12 July 2025 }}</ref> {{Clear}}
==In popular culture== * In episode 11, Season 3 ("Words and Deeds", 2007) of the TV series ''House'', firefighter Derek suffers from this syndrome.<ref>{{Cite news |author=Wired Staff |title='House' Reality Check: Broken Heart Syndrome? |url=https://www.wired.com/2007/01/house-reality-c/ |magazine=Wired |date=January 10, 2007|access-date=December 9, 2022}}</ref> * Appeared in episode 1 of season 1 of Astrid et Raphaëlle. * The name and title track of the 2021 album ''Tako Tsubo'' by French band L'Impératrice refers to the intense emotional stress that may provoke this syndrome.
== See also == * Widowhood effect
== References == {{Reflist|30em}}
== Further reading == {{refbegin}} * {{Cite journal | vauthors = Krishnan L, Marchalik D |title=Understanding Heartbreak: From Takotsubo to Wuthering Heights |url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32061-0/fulltext |journal=The Lancet |volume=392 |issue=10150 |page=812 |date=8 September 2018 |doi=10.1016/S0140-6736(18)32061-0 |s2cid=54271789 |access-date=25 September 2019|url-access=subscription }} * {{Cite journal | vauthors = Wagner JN |date=Fall 2014 |title=Death by voodoo: truth or tale? |url=https://hekint.org/2017/01/27/death-by-voodoo-truth-or-tale/ |journal=Hektoen International Journal |volume=6 |issue=4 |issn=2155-3017}} {{refend}}
== External links == * [https://takotsubo.net/ Takotsubo Network] - website for professionals and people who have experienced Takotsubo
{{Medical resources | DiseasesDB = 33976 | ICD10 = {{ICD10|I42.8}} | ICD9 = {{ICD9|429.83}} | ICDO = | OMIM = | MedlinePlus = | eMedicineSubj = article | eMedicineTopic = 1513631 | MeshID = D054549 }} {{Heart diseases}} {{Authority control}}
Category:Cardiomyopathy Category:Heart diseases Category:Articles containing video clips