REVIEW ARTICLES

e-ISSN 1643-3750
© Med Sci Monit, 2023; 29: e939020
DOI: 10.12659/MSM.939020

Received:
Accepted:
2022.11.21
2022.12.06 Epidemiology, Pathophysiology, Diagnosis,
Available online:
Published:
2023.02.10
2023.03.06 and Principles of Management of Takotsubo
Cardiomyopathy: A Review

Authors’ Contribution: ADEF 1,2 Anthony Georges Matta 1 Department of Cardiology, Toulouse University Hospital, Toulouse, France
Study Design A ADEFG 1 Didier Carrié 2 Department of Cardiology, Hôpitaux Civils de Colmar, Colmar, France
Data Collection B
Statistical Analysis C
Data Interpretation D
Manuscript Preparation E
Literature Search F
Funds Collection G

Corresponding Author: Didier Carrié, e-mail: [email protected]

Financial support: None declared
Conflict of interest: None declared

Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy, is a reversible syndrome common-

ly found among patients presenting for acute coronary syndromes, especially women. With the COVID-19 pan-
demic, the incidence of takotsubo cardiomyopathy was dramatically increased. However, this clinical cardiac
entity remains underdiagnosed, largely due to the interplay with acute coronary syndrome. The pathophysiol-
ogy of takotsubo cardiomyopathy is miscellaneous, including coronary vasospasm, microcirculatory dysfunc-
tion, catecholamine surge, and sympathetic overdrive. Diagnosing takotsubo cardiomyopathy requires a high
index of clinical suspicion and multimodality tests. To date, there are no guidelines for the management of ta-
kotsubo cardiomyopathy. Thus, available data are derived from case series, retrospective analyses, and experts’
opinions. Heart failure medicines were investigated in takotsubo cardiomyopathy patients. Evidence supports
the benefits of angiotensin-converting enzyme inhibitors and angiotensin receptors blockers use on mortal-
ity and recurrence rates, while results from use of beta-blockers are controversial. In complicated cases, ino-
tropes are preferred over vasopressors, except in the presence of left ventricular outflow tract obstruction, in
which medical therapy is limited to fluids administration and beta-blockers. Use of oral vitamin K antagonist
can benefit patients at high thrombo-embolic risk for up to 3 months. Mechanical supports are reserved for
refractory hemodynamically unstable cases. This review aims to provide an update on the epidemiology, diag-
nosis, and outcomes of takotsubo cardiomyopathy, and an extended discussion on the management of com-
plicated and non-complicated cases.

Keywords: Clinical Trial • Case Management • Takotsubo Cardiomyopathy

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2217   —   1   72

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REVIEW ARTICLES Takotsubo cardiomyopathy
© Med Sci Monit, 2023; 29: e939020

Background Epidemiology

Numerous terms like “broken heart syndrome”, “stress-induced Takotsubo cardiomyopathy accounts 1% to 3% of acute coro-
cardiomyopathy”, and “apical ballooning syndrome” have been nary syndrome [1] and 0.5% to 0.9% of ST-segment elevation
used to describe takotsubo cardiomyopathy [1]. Takotsubo car- myocardial infarction [12]. It occurs predominantly in women,
diomyopathy is a reversible acute cardiac condition related to particularly in the post-menopausal period [13]. Women over
transient regional left ventricular wall motion abnormalities 50 years old account for 80% to 90% of patients who develop
extending beyond a single epicardial coronary artery territo- takotsubo cardiomyopathy [2,14,15]. Takotsubo cardiomyopa-
ry [2]. It usually mimics acute coronary syndrome, and early thy is usually underdiagnosed, especially in patients who have
coronary angiography is generally performed [3]. Due to this co-existing coronary artery disease, largely due to the interplay
overlap between the initial clinical presentation of takotsubo between acute coronary syndrome and takotsubo cardiomyop-
cardiomyopathy and acute coronary syndrome, the Inter Tak athy [16]. Precipitating physical or emotional or mixed stressful
Diagnostic Score has been recently developed to discriminate events have been identified in two-thirds of takotsubo cardio-
these 2 different entities in the acute stage [4]. Then, accord- myopathy cases [17]. The incidence of takotsubo cardiomyopa-
ing to this score and, unlike the modified Mayo Clinic diag- thy has dramatically increased during the COVID-19 pandemic in
nostic criteria, the presence of significant coronary artery dis- association with psychological stressors such as social isolation,
ease does not exclude takotsubo cardiomyopathy diagnosis. financial issues, and anxiety [18,19]. Moreover, takotsubo cardio-
Four major patterns or variants of takotsubo cardiomyopa- myopathy has also been reported as a rare complication after ad-
thy are described in the literature: the apical ballooning form ministration of novel messenger-RNA COVID-19 vaccines [20,21].
(typical form), accounting for 80% of takotsubo cardiomyopa-
thy cases with the classical Japanese octopus trap feature [5];
mid-ventricular form with Hawk’s beak appearance [6,7]; and Pathophysiology
basal and focal forms [1,8]. Formerly considered a benign self-
limiting state, takotsubo cardiomyopathy is now known to be Although described 30 years ago, the exact pathophysiological
related to short- and long-term adverse cardiovascular out- mechanism of takotsubo cardiomyopathy remains unclear. Its
comes [9-11]. Male sex, advanced age, reduced left ventricular pathophysiology varies, including coronary vasospasm, micro-
ejection fraction below 35% at initial presentation, prolonged circulatory dysfunction, catecholamine surge, and sympathetic
QT interval on electrocardiogram, identification of a physical overdrive [22-24]. During the acute phase, the massive direct
trigger, atrial fibrillation, and development of acute complica- release of catecholamine by the sympathetic nerve endings into
tions are predictors of poor prognosis [2]. Management of ta- myocardium results in ventricular dysfunction and myocardial
kotsubo cardiomyopathy is based on anecdotal evidence from contraction band necrosis, a hallmark histological finding of ta-
experts’ opinions and case series, largely due to the absence kotsubo cardiomyopathy [25-27]. Some authors have suggest-
of randomized clinical trials [12,13]. With the era of COVID-19 ed that this local catecholamine excess dysregulates myocardi-
and the increased number of takotsubo cardiomyopathy cas- al calcium-handling and has more cardiotoxic effects than the
es, this review provides an update and short discussion about circulating one [28,29]. This local catecholamine overexpres-
the epidemiology, pathophysiology, and diagnostic tests, and sion may also explain why the catecholamine bloodstream lev-
an extended discussion about the management of complicat- el is not always elevated. The difference in the distribution of
ed and non-complicated cases based on the previously pub- b1 and b2 adrenoreceptors densities between the apical and
lished expert consensus [12], recent reviews [13], and available basal cardiac segments could explain the observed left ven-
studies. We also suggest a stepwise approach to the manage- tricular contraction abnormalities in the apical ballooning vari-
ment of takotsubo cardiomyopathy. Physicians must deal with ant of takotsubo cardiomyopathy [28,30]. Apart from the most
the underlying trigger when present, clinical cardiac manifes- established adrenergic hypothesis, it is still debated whether
tations, acute complications, and long-term recurrence risk. In coronary microvascular dysfunction is a consequence of or the
general, heart failure medications are conventionally used in primary cause of acute episodes of takotsubo cardiomyopathy.
the setting of stress-induced cardiomyopathy. Herein, we re- Repeated provocation tests showed reproducible coronary va-
view the management of and therapeutic approaches for ta- sospasm in 20% of takotsubo cardiomyopathy patients [31].
kotsubo cardiomyopathy during the acute phase to call atten-
tion to the potential associated complications and to promote
physician awareness, recognition, and care of this rare pro- Diagnostic Investigations in Takotsubo
cess. Therefore, this review aims to provide an update on the Cardiomyopathy
epidemiology, pathophysiology, diagnosis, management, and
outcomes of takotsubo cardiomyopathy, also known as stress- Electrocardiogram is the primary diagnostic test performed af-
induced cardiomyopathy. ter the first medical contact with takotsubo cardiomyopathy

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Takotsubo cardiomyopathy
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REVIEW ARTICLES

Acute chest pain

Laboratory tests (Troponine,

TTE BNP, D-Dimer, TSH, Creatinine) TTE
Diagnostic work-up

Coronary angiography

WMA corresponds WMA exceeding No CAD

to CAD CAD territory MINOCA

±LV
PCI + Probable ±LV
PCI/CABG TTC CMRI

Complicated cases
TTC

Cardiogenic choc Target therapies for

arrythmias or heart
Management of TTC

failure thrombotic Non complicated cases:

events • ACEi/ARB ± β blockers
• Statin + Aspirin if evidence of
alterosclerosis
LVOTO (20-25%) No LVOTO • VKA for 3 months if hight
• IV fkuids + • Dobutamine thromboembolic risk
Esmolol + oral • Levosimenden
β blockers

Mechanical support for refractory cases

Prognosis

Outcomes
• >90% complete recovery
• 1.8% to 10% relapse rate

Figure 1. Stepwise approach of the management of takotsubo cardiomyopathy. ECG – electrocardiogram; TTE – transthoracic
echocardiography; WMA – wall motion abnormalities; CAD – coronary artery disease; MINOCA – myocardial infarction
with non-obstructive coronary arteries; PCI – percutaneous coronary intervention;CABG – coronary artery bypass graft;
CMRI – cardiac magnetic resonance imaging; ACEi – angiotensin-converting enzyme inhibitors; ARB – angiotensin receptor
blockers; VKA – vitamin K antagonist.

patients, who commonly present with acute-onset chest ventricular ejection fraction, and assesses acute complications
pain and/or dyspnea mimicking acute coronary syndrome. (thrombus formation, mitral regurgitation, ventricular rupture,
Electrocardiogram reveals persistent or dynamic ischemic chang- and left ventricular outflow tract obstruction) [37-39]. Almost
es like ST-segment elevation, ST depression, prolonged QT in- all takotsubo cardiomyopathy patients undergo coronary an-
terval, and T wave inversion [32,33]. ECG changes are usual- giography, that reveals normal or nearly normal coronary ar-
ly not localized to a particular territory and progress over 3 teries or obstructive coronary artery disease incongruent with
stages [34-36]. The stage 1 is marked by ST-segment devia- myocardial kinetic abnormalities [13]. Co-existing coronary ar-
tion in the early hours of symptoms onset, stage 2 involves T tery disease is reported in 15% of takotsubo cardiomyopathy
wave inversion and QT interval prolongation occurring within cases [40,41]. The diagnostic investigation tests routinely end
the first 72 hours, and stage 3 is characterized by gradual re- with cardiac magnetic resonance imaging with gadolinium con-
gression of abnormalities over weeks or months. Systematic trast administration, which helps to exclude other differential
transthoracic echocardiography has several advantages: it de- diagnoses or pathologic states (eg, acute myocardial infarction
lineates ventricular wall motion abnormalities, evaluates left and myocarditis), and identifies the potential complications (eg,

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© Med Sci Monit, 2023; 29: e939020

thrombi formation, right ventricle involvement, and pericardi- the benefits of early intravenous administration of n-acetyl-
al and pleural effusion) [2,13]. Myocardial edema is the prin- cysteine followed by oral ramipril for 3 months on myocardial
cipal cardiac magnetic resonance feature of takotsubo cardio- edema reduction and cardiac function improvement [60]. The
myopathy. Levels of cardiac biomarkers (BNP/NT-pro BNP and second, an interventional trial, is evaluating outcomes of ear-
troponin T) are generally increased in a disproportion way. A ly TTC patient rehabilitation [61]. The advantages of hormone
large increase in BNP/NT-pro BNP level is associated with a therapy (estrogens) in the long-term management of TTC are
slight rise in troponin T concentration, and this discrepancy can still being studied. Angiotensin-neprilysin receptor inhibitors,
help differentiate takotsubo cardiomyopathy from acute myo- SGLT2 inhibitors, and mineralocorticoid receptor antagonists,
cardial infarction in the acute presentation. Indeed, high NT- which are recommended in the context of heart failure, have
pro BNP/troponin T ratio is suggestive of takotsubo cardiomy- not tested in TTC patients to date. Physicians must also deal
opathy, with a sensitivity of 91% and specificity of 95% [42]. with precipitating triggers when present, such as psychiatrist
referral and antidepressant prescription. To summarize, the
available evidence supports the use of ACEi or ARB in hemo-
General Management of Non-Complicated dynamically stable uncomplicated cases of TTC. The outcomes
TTC (Figure 1) from the use of all other pharmacological agents remain unclear.

Till now, there are no guidelines for the management of TTC,

and heart failure medications have been investigated in dif- Management of Complicated TTC
ferent retrospective analyses. The cardiovascular outcome of
antithrombotic therapy remains debatable, especially in the TTC may lead to serious life-threatening complications like
absence of obstructive CAD. First, the use of ACEi (angioten- acute heart failure (HF), cardiac rupture, cardiogenic shock,
sin-converting enzyme inhibitors) or ARB (angiotensin receptor thromboembolic events, and arrhythmias.
blockers) has proved positive effects on 1-year survival in TTC
patients [43] and reducing TTC recurrence risk [44,45]. Second, Acute Heart Failure
no beneficial effects for beta-blockers against mortality and
recurrence rate have been observed [41-46]. However, recent The management of acute HF after TTC is driven by the stan-
studies described long-term (up to 3-years) improvement in dard international guidelines for HF, comprising oxygen and
left ventricular systolic function [47] and reduction of cardio- respiratory support, ACEi, ARB, ARNI, beta-blockers, mineralo-
vascular mortality [48] in conjunction with beta-blockers use. corticoid receptors antagonist, and diuretics. Thus, the only dif-
Lastly, standard heart failure treatment combining beta-block- ference is to avoid pharmacological therapies for preload and
ers and ACEi or ARBs with or without aspirin and statin has afterload reduction in the setting of left ventricular outflow
revealed controversial results. While numerous studies have tract obstruction (LVOTO). While beta-blockers did not show
reported favorable result with this combination [49-51], no re- an effect on survival in HF-TTC patients [46], they showed a
duction in TTC recurrence at 3-year follow-up and an absence reduction of cardiac rupture incidence [62]. The average du-
of significant improvement in left ventricular function and du- ration of medical treatment is up to 4 weeks.
ration of hospital stay have been revealed by others [52-54].
Interestingly, the reported rate of recurrence of TTC is low [48]. Cardiogenic Shock
Focusing on antithrombotic therapy, the early use of low-mo-
lecular-weight heparin in the acute phase followed at hospi- Within the first 72 hours of hospital admission for TTC, cardio-
tal discharge by up to 3 months of oral anticoagulant treat- genic shock occurs in 11% of hospitalized patients, and 20%
ment has benefits in stroke prevention, especially in patients to 25% present with left ventricular outflow tract obstruction
at high thromboembolic risk [55,56]. Although aspirin or dual (LVOTO) [63]. Positive inotropic agents (eg, dopamine/dobuta-
antiplatelet (aspirin + clopidogrel) intake may reduce the ma- mine) are preferred over sympathomimetic cholinergic vaso-
jor cardiovascular events including stroke [48], a recent study pressors (eg, ephedrine/norepinephrine) to restore cardiac func-
conducted on 1553 TTC patients found no effects of aspirin tion and blood pressure. Exacerbated in-hospital and long-term
use on prognosis and complications development [57]. Thus, mortality rates have been observed with catecholamine admin-
statins and aspirin are conventionally recommended in the istration for circulatory support in hemodynamically unstable
setting of co-existing CAD [2]. A fast reduction in inflammato- TTC patients [64]. Mechanical support is considered for refrac-
ry biomarkers was associated with 600 mg daily use of alpha- tory and/or severe cases with and without LVOTO. However, it
lipoic acid [58]. In general, the optimal duration of TTC treat- is mandatory to check for LVOTO before initiating therapy, as
ment ranges from 3 months to 1 year, depending on cardiac this condition contraindicates inotropic drugs and intra-aortic
function recovery [59]. There are 2 ongoing prospective ran- balloon pump. In case of LVOTO, the first medical treatment
domized clinical trials. The first, NACRAM trial, is investigating is limited to fluid resuscitation and beta-blockers. Santoro et

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Takotsubo cardiomyopathy
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REVIEW ARTICLES

al revealed the efficacy of early intravenous administration of the reported prevalence of relapse ranges from 1.8% to 10%
esmolol followed by daily bisoprolol in decreasing LVOTO gra- [43,45,69,70]. Women with advanced age (›50 years), severely
dient and alleviating obstruction [65]. Intravenous injection of altered left cardiac function, vulnerability to emotional stress,
levosimendan, a calcium-sensitizing agent and ATP-potassium and fluctuations in cardiac baroreceptors were identified as
channel-opening mediator, significantly improves left ventricu- independent predictors of recurrence [71]. In addition, male
lar function in the setting of TTC-cardiogenic shock [66]. sex, high-grade Killip on hospital admission, and diabetes
mellitus were recognized as independent predictors of mor-
Thromboembolic Events tality [72]. A recently published study showed lower mortali-
ty and recurrence rates at 5.2-year follow-up in TTC patients
Left ventricular thrombus formation and subsequent systemic treated with beta-blockers only compared to those receiving
embolization occur in 1$ to 2% of TTC cases, especially in those ACEi or ARB alone [70]. Finally, modifying lifestyle by reduc-
with severely altered left ventricular systolic function. When left ing caffeine consumption and smoking cessation help to pre-
ventricular thrombus is detected either by transthoracic echo- vent TTC recurrence [73].
cardiography or cardiac MRI, oral anticoagulation therapy based
on vitamin K antagonist is recommended for at least 3 months
to prevent thrombus migration [55]. The efficacy of novel non- Conclusions
vitamin K oral anticoagulant has not been studied in TTC.
To summarize, diagnosing TTC requires a high index of clin-
Arrhythmias ical suspicion and multimodality tests. The management of
TTC is personalized care analyzed on a case-by-case basis.
Ventricular tachycardia or ventricular fibrillation represents A primary diagnostic work-up is essential to screen for the
two-thirds of TTC-associated arrhythmia [67,68]. Closed QT in- presence of potential complications, especially for LVOTO,
terval and telemetry monitoring during the acute phase were which may drive the therapeutic approach. ACEi/ARB and
suggested. Intravenous magnesium is the first therapeutic ap- beta-blockers are commonly used in non-complicated pa-
proach for torsade de pointes, followed by isoproterenol for tients, while mechanical supports, vasopressors, and ino-
non-responders. Amiodarone is the preferred anti-arrhythmic tropes are reserved for severe cases. Statins and aspirin are
drug compared to other drugs that may also prolonged QT in- advised if atherosclerotic signs co-exist. Long-term manage-
terval. Finally, the question concerning permanent pacemak- ment includes screening for triggers or precipitant factors,
er or defibrillator implantation versus temporary device use in monitoring for recurrence, and cardiac rehabilitation. Further
case of severe arrhythmias (high-grade atrio-ventricular block, prospective randomized clinical trials are warranted to es-
ventricular arrhythmias) is still debatable [59]. tablish standard guidelines.

Declaration of Figures’ Authenticity

Takotsubo Cardiomyopathy Patient Outcomes
All figures submitted have been created by the authors, who
The overall prognosis of TTC is favorable with complete recov- confirm that the images are original with no duplication and
ery in more than 90% of patients within 1-2 months. However, have not been previously published in whole or in part.

References:
1. Matta A, Delmas C, Campelo-parada F, et al. Takotsubo cardiomyopathy. 7. Matta A, Roncalli J, Elbaz M, et al. Mid-ventricular takotsubo cardiomy-
Rev Cardiovasc Med. 2022;23:38 opathy with hawk’s beak appearance: A case report. Am J Case Rep.
2. Ghadri J, Wittstein IS, Prasad A, et al. International expert consensus doc- 2020;21:e919563
ument on takotsubo syndrome (Part I): Clinical characteristics, diagnostic 8. Ennezat PV, Pesenti-Rossi D, Aubert JM, et al. Transient left ventricular basal
criteria, and pathophysiology. Eur Heart J. 2018;39:2032-46 dysfunction without coronary stenosis in acute cerebral disorders: A novel
3. Luscher TF, Templin C. Is takotsubo syndrome a microvascular acute coro- heart syndrome (inverted takotsubo). Echocardiography. 2005;22:599-602
nary syndrome? Towards of a new definition. Eur Heart J. 2016;37:2816-20 9. Redfors B, Jha S, Thorleifsson S, et al. Short- and long-term clinical out-
4. Ghadri JR, Cammann VL, Jurisic S, et al. A novel clinical score (Inter TAK comes for patients with takotsubo syndrome and patients with myocardi-
Diagnostic Score) to differentiate takotsubo syndrome from acute coronary al infarction: A report from the swedish coronary angiography and angio-
syndrome: Results from the International Takotsubo Registry. Eur J Heart plasty registry. J Am Heart Assoc. 2021;10:e017290
Fail. 2017;19:1036-42 10. Uribarri A, Nunez-Gil IJ, Conty DA, et al. Short- and long-term prognosis of
5. Eitel I, von Knobelsdorff-Brenkenhoff F, Bernhardt P, et al. Clinical charac- patients with takotsubo syndrome based on different triggers: Importance
teristics and cardiovascular magnetic resonance findings in stress (takot- of the physical nature. J Am Heart Assoc. 2019;8:e013701
subo) cardiomyopathy. JAMA. 2011;306:277-86 11. Ghadri JR, Kato K, Cammann VL, et al. Long-term prognosis of patients with
6. Roncalli J, Carrie D, Fauvel JM, Losordo D. A hawk’s beak to identify the new takotsubo syndrome. J Am Coll Cardiol. 2018;72:874-82
transient midventricular Tako-Tsubo syndrome. Int J Cardiol. 2008;127:179-80 12. Sattar Y, Woei Siew KS, Connerney M, et al. Management of takotsubo syn-
drome: A comprehensive review. Cureus. 2020;12:e6556

Indexed in: [Current Contents/Clinical Medicine] [SCI Expanded] [ISI Alerting System]
This work is licensed under Creative Common Attribution-
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[Chemical Abstracts/CAS]
 Matta A.G. and Carrié D.:
REVIEW ARTICLES Takotsubo cardiomyopathy
© Med Sci Monit, 2023; 29: e939020

13. Assad J, Femia G, Pender P, et al. Takotsubo syndrome: A review of 40. Uribarri A, Nunez-Gil IJ, Conty DA, et al. Short- and long-term prognosis of
presentation, diagnosis and management. Clin Med Insights Cardiol. patients with takotsubo syndrome based on different triggers: Importance
2022;16:11795468211065782 of the physical nature. J Am Heart Assoc. 2019;8:e013701
14. Cammann VL, Szawan KA, Stahli BE, et al. Age-related variations in takot- 41. Redfors B, Jha S, Thorleifsson S, et al. Short- and long-term clinical out-
subo syndrome. J Am Coll Cardiol. 2020;75:1869-77 comes for patients with takotsubo syndrome and patients with myocardi-
15. Pelliccia F, Kaski JC, Crea F, Camici PG. Pathophysiology of takotsubo syn- al infarction: A report from the swedish coronary angiography and angio-
drome. Circulation. 2017;135:2426-41 plasty registry. J Am Heart Assoc. 2021;10:e017290
16. Napp LC, Cammann VL, Jaguszewski M, et al. Coexistence and outcome of 42. Fröhlich GM, Schoch B, Schmid F. Takotsubo cardiomyopathy has a unique
coronary artery disease in takotsubo syndrome. Eur Heart J. 2020;41:3255-68 cardiac biomarker profile: NT-proBNP/myoglobin and NT-proBNP/tropo-
nin T ratios for the differential diagnosis of acute coronary syndromes and
17. Gianni M, Dentali F, Grandi AM, et al. Apical ballooning syndrome or takot- stress induced cardiomyopathy. Int J Cardiol. 2012;154:328-32
subo cardiomyopathy: A systematic review. Eur Heart J. 2007;27:1523-29
43. Templin C, Ghadri JR, Diekmann J, et al. Clinical features and outcomes of
18. Jabri A, Kalra A, Kumar A, et al. Incidence of stress cardiomyopathy during takotsubo (stress) cardiomyopathy. N Engl J Med. 2015;373:929-38
the coronavirus disease 2019 pandemic. JAMA Netw open. 2020;3:e2014780
44. Regnante RA, Zuzek RW, Weinsier SB, et al. Clinical characteristics and four-
19. Eftekharzadeh P, Patel A, Sokolova E, et al. Takotsubo cardiomyopathy: A year outcomes of patients in the Rhode Island takotsubo cardiomyopathy
COVID-19 complication. Cureus. 2022;14:e22803 registry. Am J Cardiol. 2009;103:1015-19
20. Ahmed SK, Mohamed MG, Essa RA, et al. Global reports of takotsubo (stress) 45. Singh K, Carson K, Usmani Z, et al. Systematic review and metanalysis of
cardiomyopathy following COVID-19 vaccination: A systematic review and incidence and correlates of recurrence of takotsubo cardiomyopathy. Int J
meta-analysis. Int J Cardiol Heart Vasc. 2022;43:101108 Cardiol. 2014;174:696-701
21. Fazlollahi A, Zahmatyar M, Noori M, et al. Cardiac complications following 46. Isogai T, Matsui H, Tanaka H, et al. Early b-blocker use and in-hospital mor-
mRNA COVID-19 vaccines: A systematic review of case reports and case tality in patients with Takotsubo cardiomyopathy. Heart. 2016;34:161-66
series. Rev Med Virol. 2022:33:e2318
47. Ghalyoun BA, Guragai R, Garris R, et al. Abstract11626: Faster recovery in
22. Hasan SM, Patel JD, Faluk M, et al. Takotsubo cardiomyopathy and its vari- takotsubo with prior beta-blocker use. Circulation. 2019;140
ants: A case series and literature review. J Community Hosp Intern Med
PersPerspect. 2020;10:210-15 48. Medias JE. Cardioselective ultra-short-acting b-blockers for patients
with takotsubo syndrome?: Letters to the editor. Geriatr Gerontol Int.
23. Boyd B, Solh T. Takotsubo cardiomyopathy. JAAPA. 2020;33:24-29 2018;18:816-17
24. Amin HZ, Amin LZ, Pradipta A. Takotsubo cardiomyopathy: A brief review. 49. Yayehd K, N’daNW, Belle L, et al. Management of Takotsubo cardiomyop-
J Med Life. 2020;13:3-7 athy in non-academic hospitals in France: The observational French syn-
25. Kume T, Kawamoto T, Okura H, et al. Local release of catecholamines from dromes of takotsubo (OFSETT) study. Arch Cardiovasc Dis. 2016;109:4-12
the hearts of patients with tako-tsubo-like left ventricular dysfunction. Circ 50. Abanador-Kamper N, Kamper L, Wolfertz J, et al. Evaluation of therapy man-
J. 2008;72:106-8 agement and outcome in takotsubo syndrome. BMC Cardiovasc Disord.
26. Akashi YJ, Nakazawa K, Sakakibara M, et al. 123i-mibg myocardial scin- 2017;17:225
tigraphy in patients with “takotsubo” cardiomyopathy. J Nucl Med. 51. Dias A, Franco E, Koshkelashvili N, et al. Antiplatelet therapy in takotsubo
2004;45:1121-27 cardiomyopathy: Does it improve cardiovascular outcomes during index
27. Mizutani K, Shioya A, Hirose Y, et al. Serious takotsubo cardiomyopathy: event?. Heart Vessels. 2016;31:1285-90
An autopsy case presenting severe irreversible myocardial damage after 52. Santoro F, Ieva R, Musaico F, et al. Lack of efficacy of drug therapy in pre-
frequent episodes of recurrence. Diagn Pathol. 2020;15:90 venting takotsubo cardiomyopathy recurrence: A meta-analysis. Clin Cardiol.
28. Mori H, Ishikawa S, Kojima S, et al. Increased responsiveness of left ventricu- 2011;34:672-76
lar apical myocardium to adrenergic stimuli. Cardiovasc Res. 1993;27:192-98 53. Fazio G, Pizzuto C, Barbaro G, et al. Chronic pharmacological treatment in
29. Nef HM, Mollmann H, Troidl C, et al. Abnormalities in intracellular Ca2+ takotsubo cardiomyopathy. Int J Cardiol. 2008;127:121-23
regulation contribute to the pathomechanism of tako-tsubo cardiomyop- 54. Kummer M, ElBattrawy I, Ansari U, et al. The use of beta blockers in takot-
athy. Eur Heart J. 2009;30:2155-64 subo syndrome as compared to acute coronary syndrome. Front Pharmacol.
30. Vriz O, Minisini R, Citro R, et al. Analysis of beta1 and beta2-adrenergic re- 2020;11:681
ceptors polymorphism in patients with apical ballooning cardiomyopathy. 55. Santoro F, Stiermaier T, Tarantino N, et al. Left ventricular thrombi in takot-
Acta Cardiol. 2011;66:787-90 subo syndrome: Incidence, predictors, and management: Results from the
31. Rivero F, Cuesta J, Garcia-Guimaraes M, et al. Time-related microcirculato- GEIST (German Italian Stress Cardiomyopathy) registry. J Am Heart Assoc.
ry dysfunction in patients with takotsubo cardiomyopathy. JAMA Cardiol. 2017;6:006990
2017;2:699-700 56. De Gregorio C. Cardioembolic outcomes in stress-related cardiomyopathy
32. Ghadri JR, Wittstein IS, Prasad A, et al. International expert consensus doc- complicated by ventricular thrombus: A systematic review of 26 clinical
ument on takotsubo syndrome (Part II): Diagnostic workup, outcome, and studies. Int J Cardiol. 2010;141:11-17
management. Eur Heart J. 2018;39:2047-62 57. D’Ascenzo F, Gili S, Bertaina M, et al. Impact of aspirin on takotsubo syn-
33. Yoshikawa T. Takotsubo cardiomyopathy, a new concept of cardiomyopa- drome: A propensity score-based analysis of the InterTAK Registry. Eur J
thy: Clinical features and pathophysiology. Int J Cardiol. 2015;182:297-303 Heart Fail. 2020;22:330-37
34. Namgung J. Electrocardiographic findings in takotsubo cardiomyopathy: 58. Marfella R, Barbieri M, Sardu C, et al. Effects of a-lipoic acid therapy on
ECG evolution and its difference from the ECG of acute coronary syndrome. sympathetic heart innervation in patients with previous experience of tran-
Clin Med Insights Cardiol 2014;8:29-34 sient takotsubo cardiomyopathy. J Cardiol. 2016;67:153-61
35. Frangieh AH, Obeid S, Ghadri JR, et al. Ecg criteria to differentiate between 59. Bairashevskaia AV, Belogubova SY, Kondratiuk MR, et al. Update of takot-
takotsubo (stress) cardiomyopathy and myocardial infarction. J Am Heart subo cardiomyopathy: Present experience and outlook for the future. Int J
Assoc. 2016;5:e003418 Cardiol Heart Vasc. 2022;39:100990
36. Scally C, Choo W, Rudd A, et al. The early dynamic of ecg in takotsubo syn- 60. Ong GJ, Nuguyen TH, Stansborough J, et al. The N-AcetylCysteine and
drome presenting with st-elevation: A comparison with age and gender- RAMipril in Takotsubo Syndrome Trial (NACRAM): Rationale and design of
matched ST-elevation myocardial infarction. Int J Cardiol. 2020;320:7-11 a randomised controlled trial of sequential NAcetylcysteine and ramipril
37. Citro R, Lyon AR, Meimoun P, et al. Standard and advanced echocardiog- for the management of takotsubo Syndrome. Contemporary Clinical Trials.
raphy in takotsubo (stress) cardiomyopathy: Clinical and prognostic impli- 2020;90:105894
cations. J Am Soc Echocardiogr. 2015;28:57-74 61. Dawson D. Physical exercise and mental wellbeing rehabilitation for acute
38. De Gregorio C, Grimaldi P, Lentini C. Left ventricular thrombus formation stress-induced takotsubo cardiomyopathy: The PLEASE Study (PLEASE).
and cardioembolic complications in patients with takotsubo-like syndrome: 2021
A systematic review. Int J Cardiol. 2008;131:18-24 62. Kumar S, Kaushik S, Nautiyal A, et al. Cardiac rupture in takotsubo cardio-
39. Akashi YJ, Tejima T, Sakurada H, et al. Left ventricular rupture associated myopathy: A systematic review. Clin Cardiol. 2011;34:672-76
with takotsubo cardiomyopathy. Mayo Clin Proc. 2004;79:821-24

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Matta A.G. and Carrié D.:
Takotsubo cardiomyopathy
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REVIEW ARTICLES

63. P’keefe EL, Torres-Acosta N, O’keefe JH, et al. Takotsubo syndrome: 68. Brown KH, Trohman RG, Madias C. Arrhythmias in takotsubo cardiomyop-
Cardiotoxic stress in the COVID era, Mayo Clinic proceedings: innovations. athy. Card Electrophysiol Clin. 2015;7:331-40
Qual Outcomes. 2020;4:775-85 69. Kato K, Kitahara H, Kobayashi Y. Recurrence of takotsubo cardiomyopathy.
64. Ansari U, Elbattrawy I, Fastner C, et al. Clinical outcomes associated with International Cardiovascular Forum Journal. 2016;5:50-52
catecholamine use in patients diagnosed with takotsubo cardiomyopathy. 70. Lau C, Chiu S, Nayak R, et al. Survival and risk of recurrence of takotsubo
BMC Cardiovasc Disord. 2018;18:54 syndrome. Heart. 2021;107:1160-66
65. Santoro F, Ieva R, Ferraretti A, et al. Hemodynamic effects, safety, and fea- 71. Sager HB, Schunkert H, Kurowski V. Recurrent mid-ventricular Tako-Tsubo
sibility of intravenous esmolol infusion during Takotsubo cardiomyopathy cardiomyopathy: Three episodes of a uniform cardiac response to varying
with left ventricular outflow tract obstruction: Results from a multicenter stressors. Int J Cardiol. 2011;152:22-24
registry. Cardiovasc Ther. 2016;34:161-66
72. Stiermaier T, Moeller C, Oehler K, et al. Long-term excess mortality in takot-
66. Santoro F, Ieva R, Ferraretti A, et al. Safety and feasibility of levosiemndan subo cardiomyopathy: Predictors, causes and clinical consequences. Eur J
administration in Takotsubo cardiomyopathy: A case series. Cardiovasc Heart Fail. 2016;18:650-56
Ther. 2013;31:133-37
73. Harris KM, Rosman L, Burg MM, Salmoirago-Blotcher. Modifiable lifestyle
67. Moller C, Eitel C, Thiele H, Eitel I, Stiermaier T. Ventricular arrhythmias in factors in women with Takotsubo syndrome: A case-control study. Heart.
patients with Takotsubo syndrome. J Arrhythmia. 2018;34:369-75 2020;49:524-29

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