CONTENTS
- Epidemiology
- Symptoms
- Diagnostic studies
- Diagnostic approach
- Treatment
- Prognosis
- Pathophysiology
- Podcast
- Questions & discussion
- Pitfalls
primary Takotsubo syndrome (initial presenting problem)
- Underlying etiology in ~2% of patients who present with chest pain and troponin elevation, and ~5% of women with this presentation. (34362020, 35344411)
- ~90% of patients are women.
- ~90% of patients are >50 years old. (35344411)
- Identifiable stressors are present in 70% of cases (physical or emotional). However, this leaves about 30% of patients with no identifiable stressor. Pleasant emotional stressors have also been reported to cause Takotsubo. (35002350)
- Prior history of Takotsubo cardiomyopathy increases risk of future episodes.
secondary Takotsubo syndrome
This is extremely common in ICU, affecting perhaps ~20% of patients in one series. (16002949) Takotsubo syndrome may result from a wide variety of physiological stressors:
- Post-cardiac arrest.
- Neurologic disorders (e.g., subarachnoid hemorrhage, status epilepticus, stroke).
- Brain death (may limit candidacy for cardiac donation).
- Sepsis.
- Respiratory failure (especially asthma or COPD, with excess beta-2 agonists).
- Autonomic instability, catecholamine excess.
- Autonomic nervous system manipulation (e.g., carotid artery surgery, radical neck dissection).
- Poisoning (e.g., sympathomimetic overdose), withdrawal.
- Surgery.
- Trauma.
- Endocrine emergencies (e.g., pheochromocytoma, thyrotoxicosis, adrenal crisis).
- Overall, symptoms are usually more prominent with primary Takotsubo syndrome. In secondary Takotsubo syndrome, these symptoms may often be camouflaged by features of the primary illness (e.g., intubation, sedation).
- Anginal chest pain (e.g., diaphoresis, chest pressure).
- Arrhythmia (including polymorphic ventricular tachycardia, VF, AF, bradycardia, asystole).
- Syncope or palpitations.
- Cardiac arrest.
- Heart failure
- Dyspnea, pulmonary edema.
- Cardiogenic shock (in intubated ICU patients, this may be the initial presentation.)
rhythm
- Atrial fibrillation can occur.
- Malignant arrhythmia can occur (either Torsade de Pointes or monomorphic ventricular tachycardia).
intervals
- QT prolongation is often pronounced (QTc > 500ms) and this predisposes to TdP or VF. QT prolongation usually normalizes within 48 hours. (35002350)
- LBBB may be seen.
typical evolution of ECG changes
- Stage #1: Diffuse STE:
- This may last hours or days.
- In neurologic catastrophes (e.g., subarachnoid hemorrhage), this phase can be brief or perhaps nonexistent.
- Stage #2: Progressive TWI and QTc prolongation
- Occurs within ~1-3 days and peaks at ~2-6 days. (35344411)
- QTc prolongation correlates with an increased risk of ventricular arrhythmias.
- Stage #3: Gradual resolution over weeks-months. (35344411)
Takotsubo cardiomyopathy in STE phase (Stage #1)
key features of Takotsubo in STE phase
- 🔑 STE is often maximal in V3-V5 but can be diffuse (including II).
- 🔑 Lack of STE in V1 (~80% sensitive & specific for differentiation from anterior MI). (36074030)
- 🔑 aVR usually has STD.
- 🔑 No reciprocal STD or Q-waves.
- 🔑 QT may be dramatically prolonged.
- Related differential diagnoses:
description of findings
- STE:
- Usually most notable in V3-V6, but STE in II is also characteristic (this suggests Takotsubo, but can also result from wraparound LAD occlusion).
- STE has a lower magnitude than is typically seen with anterior OMI.
- T-waves:
- Prominent T-waves may be typically seen throughout the ECG.
- TWI can also be seen (usually, TWI develops later, but the various phases of stress cardiomyopathy may overlap somewhat).
- J-waves:
- J-waves occur in ~35% of patients with Stage 1 Takotsubo cardiomyopathy. They indicate an elevated risk of polymorphic VT (discussed further below: ⚡️).
- J-waves may occur in both Takotsubo cardiomyopathy and MI, so this doesn't differentiate the two pathologies. (further discussion of J-waves here: 📖)
ddx of Takotsubo vs. OMI
- ⚠️ Caution: ECG usually isn't adequate to confidently differentiate MI from Takotsubo cardiomyopathy, so cardiac catheterization is often required.
- [1/5] If there is global STE:
- Takotsubo CM: Suggested by widespread STE (in inferior, anterior, and lateral territories)
- MI: Suggested by more focal STE.
- [2/5] The usual distribution of ST changes:
- Takotsubo:
- STE is often maximal in V3-V5.
- Only 20% have STE in V1.
- aVR often has STD.
- MI:
- STE is more often maximal in V2-V4.
- 80% of patients will have STE in V1.
- aVR often has STE.
- Takotsubo:
- [3/5] Reciprocal STD?
- The absence of reciprocal STD suggests Takotsubo. Takotsubo tends to cause STE in the frontal leads (especially I, II, and aVF) without any reciprocal STD in aVL.
- Reciprocal STD would suggest MI.
- [4/5] If present, severely prolonged QT favors Takotsubo:
- In one series, the mean QTc for Takotsubo was 567 (+/- 80) vs. 489 (+/- 60) for MI. (20510222) So there's a lot of overlap – but a massive QT suggests Takotsubo.
- [5/5] Q-waves would favor an MI (these usually aren't seen in Takotsubo).

Takotsubo cardiomyopathy in TWI phase (Stage #2)
ECG findings of TWI-predominant takotsubo:
- [1] Diffuse TWI, often involving a large number of leads (e.g., V2-V6, I, II, aVL).
- (⚠️ More restricted distribution may suggest ischemia.)
- [2] QT prolongation often occurs; it may be dramatic.
- [3] TWI may be massive (>5-10 mm).
- The differential of giant TWI is here: 📖
- [4] Roller-coaster T-waves: T-waves are often asymmetric, with a gradual downslope followed by a rapid up-slope.
- Other features that may be seen:
- [i] Some ST depression may occur.
- [ii] Low voltage may occur in Lead I and aVL. (Further discussion of Lead I sign: 📖)
the main differential diagnosis is ischemic TWI
- Ischemia can closely mimic this pattern (in some cases, it may be impossible to differentiate takotsubo vs. ischemia).
- If TWI is more restricted (rather than diffuse), then this would favor a diagnosis of ischemia.


ECG in reverse Takotsubo
Reverse Takotsubo cardiomyopathy refers to a situation where the base is hypokinetic and the apex is hyperkinetic. In some cases, this may occur following a more typical presentation (due to exhaustion of the base of the heart). This may evolve over time a bit, but it doesn't seem to develop large TWI (the way the apical form of Takotsubo cardiomyopathy does).
ECG findings
- Widespread STD:
- STD in the inferior leads, ~V3-V6.
- STE may occur in aVR and aVL.
- (2) Low voltage may occur in the high lateral leads (I, aVL).
- (3) QTc prolongation may give this a more “spread-out” appearance than ischemia. (27755515)
Takotsubo cardiomyopathy presenting with prominent T-waves
- Takotsubo is usually associated with prominent T-wave inversion, or diffuse STE.
- Rarely, Takotsubo can present with a predominant finding of diffuse, large, upright T-waves.
- Useful clues:
- QTc may be prolonged.
- A prominent U-wave may be present, or the T-wave may appear bifid and complex.
Different echocardiographic patterns might represent different stages in the evolution of Takotsubo syndrome. Initially the apex is predominantly involved. At a later time point, the apex may recover – but meanwhile a secondary stress cardiomyopathy has developed in the basal myocardium.
[#1/4] apical ballooning type (~80%)
- The classic pattern is akinesia of the apex, with hypercontractility of the base.
- This “apical ballooning pattern” may mimic LAD-distribution ischemia.
- If circumferential wall motion abnormalities are present and extend beyond any single coronary artery territory, this argues against MI. However, echocardiographic differentiation with 100% accuracy may not be possible.
- LV outflow tract obstruction (LVOTO) with systolic anterior motion of the mitral valve may occur due to basal hyperkinesis.
- This is important to recognize, as it has hemodynamic implications for management (more on this below).
[#2/4] mid ventricular wall pattern (~15%)
- Hypokinesis only involving the mid-ventricular region with normal apical function.
[#3/4] basal (“reversed”) pattern (~2%)
- Basal hypokinesis, with normal function of the apex.
[#4/4] focal variants (1.5%)
- Most often this involves isolated anterolateral segment dysfunction.
- Echocardiographically, this is the closest mimic of an occlusive MI.
RV involvement
- ~15% of cases may involve the RV. (34362020)
- This is a poor prognostic sign.
CMRI findings in Takotsubo cardiomyopathy
- (1) Late gadolinium enhancement:
- Typically has no late gadolinium enhancement.
- Rarely causes a thin, transmural band of birossi at the hinge point between the hyperkinetic base and apex. (35344411)
- (2) Intense, transmural myocardial edema is seen widely throughout the myocardium (e.g., on T2 sequences).
- Edema resolves over weeks-months, but often more gradually than improvement in LV ejection fraction.
differentiation from MI or myocarditis:
- MI: typically shows late gadolinium enhancement (LGE) in a focal distribution:
- LGE is either subendocardial or transmural.
- LGE should be located in a coronary artery distribution.
- Myocarditis: typically shows late gadolinium enhancement (LGE) in a patchy distribution (although the exact distribution will vary depending on the type of myocarditis). Further discussion of CMRI in myocarditis here: 📖
information for prognosis & management:
- Evaluation for mural thrombus.
- Evaluation of LV function.
- Detection of LV outflow tract obstruction.
troponin
- Elevated in 90% of cases of Takotsubo cardiomyopathy.
- Disproportionately low compared to the magnitude of wall motion abnormalities.
BNP
- Elevated in ~80% of patients.
- The diagnostic value of BNP is highly dubious, since it is extremely nonspecific (especially among critically ill patients, most of whom will have an elevated BNP).
differential diagnosis
- Myocardial infarction:
- OMI (occlusive myocardial infarction).
- NOMI (non-occlusive myocardial infarction).
- Demand (type II) myocardial infarction in the context of chronic systolic failure.
- MINOCA (myocardial ischemia with non-occlusive coronary arteries), including:
- Atherosclerotic disease.
- Coronary thromboembolism.
- Spontaneous coronary artery dissection.
- Coronary artery vasospasm.
- Any other cause of acute systolic heart failure, such as:
- Myocarditis.
- Postpartum cardiomyopathy.
diagnostic approach
- [1] If emergent PCI is needed (e.g., presenting ECG mimics an OMI):
- Patients with STE that is concerning for MI require acute PCI.
- Note that it is often impossible to differentiate between an MI and Takotsubo based on a few ECGs.
- If PCI is performed, then Takotsubo may often be diagnosed on a combination of echocardiographic, ECG, and cardiac catheterization data.
- [2] If emergent PCI isn't needed (e.g., presenting ECG doesn't have worrisome STE):
- MRI may be a powerful diagnostic modality to differentiate Takotsubo from alternative diagnoses (e.g., myocarditis, MI).
- A relatively moderate troponin elevation in the context of dramatic wall motion abnormalities would support Takotsubo cardiomyopathy (as opposed to myocardial infarction).
- Characteristic ECG evolution over time may help support a diagnosis of Takotsubo cardiomyopathy.
- ⚠️ Please note that not all patients with new wall motion abnormalities and a negative cardiac catheterization have Takotsubo cardiomyopathy. There are numerous other possibilities (e.g., myocarditis and MINOCA).
[1] evaluate and treat any underlying problems
- Many patients may have secondary Takotsubo cardiomyopathy, which can result from a variety of emergent problems (as listed above: 📖)
- Evaluate for an underlying cause and treat if possible.
[2] consider anticoagulation for classic apical ballooning form
- The classical apical ballooning form of stress cardiomyopathy carries a ~5% risk of mural thrombus formation within the apex. This risk varies depending on disease severity and the degree of blood stasis within the cardiac apex.
- Short-term anticoagulation should be considered for patients with a large apical akinetic zone and severe LV dysfunction.
- Thrombus formation is greatest within 2-5 days of symptom onset, but has been described up to 14 days after onset. The best way to assess risk may be serial echocardiography to determine when ventricular function improves.
- There is no high-quality evidence on this. Treatment decisions should be individualized based on clinical judgement, the extent of echocardiographic findings, and bleeding risks.
[3] arrhythmia prevention and/or management
incidence of various arrhythmias:
- Atrial fibrillation is the most common (~20%).
- Ventricular arrhythmia (2-10%) – may include polymorphic VT, ventricular fibrillation.
- (Complete heart block can occur, but is rare.)
risk factors for malignant arrhythmias:
- QTc >500 ms.
- J-wave (hazard ratio of 3.5; risk approaching 50%). 📖 (Choi et al 2020)
- QRS duration > 105 ms. (29627435)
arrhythmia prevention
- Monitor with telemetry.
- Optimize potassium and magnesium levels (K >3.5 mM, Mg >>2 mg/dL).
- Review the medication list and discontinue any QT-prolonging medications.
management of polymorphic VT in Takotsubo cardiomyopathy
- ⚠️ Optimal treatment is unclear and expert opinion from electrophysiology should be considered. Electrophysiologically, this seems to be most closely related to polymorphic VT that occurs in the context of acute myocardial infarction (e.g., both may be associated with J-waves and QT prolongation). This doesn't seem to simply reflect torsade de pointes due purely to QT prolongation.
- Magnesium administration seems safe and reasonable, although it's efficacy is unknown.
- Beta-blockers are suggested by some authors, and this seems reasonable as well (if hemodynamically tolerated). (30167007) Beta-blockers could worsen torsade de pointes – but polymorphic VT in Takotsubo cardiomyopathy seems to have a distinct mechanism.
- If an IV antiarrhythmic infusion was needed, lidocaine might be a rational selection (with the advantage that it won't aggravate QT prolongation). However, amiodarone could be reasonable as well.
[4a] hemodynamically stable patient
beta-blocker
- Beta-blockade is probably advisable if LVEF is reduced and the patient is hemodynamically stable enough to tolerate this.
- (1) This may reduce stress on myocardium and also reduce incidence of arrhythmias.
- (2) Given the centrality of excess adrenergic tone in the pathophysiology of this disease, a beta-blocker makes sense.
- Beta-blockade may be especially useful in patients with LV outflow tract obstruction (wherein a reduced heart rate may improve diastolic ventricular filling).
- However – If the LVEF is severely reduced, beta-blockers may carry a risk of precipitating cardiogenic shock. Thus, as in patients with advanced heart failure, these should be used cautiously and up-titrated gradually.
afterload reduction
- This may be useful, particularly in patients with hypertension.
- An ACE inhibitor is an attractive option. However, if there are concerns regarding renal function, then a combination of hydrazine plus isosorbide dinitrate may be safer (at least in the short term, until the patient has stabilized).
- Afterload reduction is contraindicated if there is dynamic LV outflow tract obstruction on echocardiogram (LVOTO; more on this below). Likewise, overly aggressive afterload reduction could theoretically cause the development of LVOTO, even if it isn't initially present (LVOTO is a reversible physiologic phenomenon).
[4b] hemodynamically unstable with LVOTO (LV outflow tract obstruction)
basic concepts
- LVOTO occurs when the base of the heart contracts vigorously, causing the turbulent flow of blood in the aortic outflow tract to pull the anterior leaflet of the mitral valve anteriorly (causing mitral regurgitation). This may occur in the classic (apical) variant of Takotsubo cardiomyopathy.
- LVOTO occurs in ~10% of patients with takotsubo cardiomyopathy. (34362020)
- LVOTO is important to recognize, because these patients respond differently to treatments compared to most patients with heart failure:
- Afterload reduction (e.g., nitroglycerine) and diuretics will make LVOTO worse.
- Beta-blockade and fluid loading may improve LVOTO.
- Hypotension in the context of LVOTO may respond to a pure vasoconstrictor (e.g., phenylephrine). In contrast, inotropic agents may exacerbate LVOTO.
management
- Fluid resuscitation if there is evidence of hypovolemia.
- Support the mean arterial pressure with pure vasoconstrictors as needed (e.g., phenylephrine).
- Cautious beta-blockade, especially if there is substantial tachycardia (e.g., esmolol infusion). (26946520) If this is tolerated, it may be transitioned to longer-acting beta-blockers.
- Avoid IABP (intra-aortic balloon pump).
- (More on the management of LVOTO here.📖)
[4c] hemodynamically unstable without LVOTO (LV outflow tract obstruction)
- Overall, this is similar to the management of other patients with severe systolic heart failure.📖
- Inotropes are a double-edged sword here:(29554866)
- Inotropes may improve cardiac output and organ perfusion. However, increased inotropy can potentially cause LVOTO physiology, exacerbating matters. (32042529)
- The pathophysiological cause of Takotsubo cardiomyopathy is excess sympathetic tone, so inotropes could potentially exacerbate this.
- Inotrope use could theoretically increase the risk of ventricular arrhythmia.
- Overall – the lowest possible dose of inotrope should be used which maintains systemic perfusion. When possible, volume resuscitation and phenylephrine may be used to support perfusion, without increasing stress on the myocardium.
- European Society of Cardiology guidelines suggest a preference for milrinone over catecholamines. (32469155)
- In severe shock, mechanical support (e.g., ECMO) may be used as a bridge to recovery.
- In-hospital mortality is 2-5%, so this isn't a benign entity (this mortality is similar to acute coronary syndrome). Adverse outcomes may be driven by heart failure, malignant arrhythmias, and cardioembolic complications.
- LVEF generally recovers by 12 weeks, sometimes much faster. However, mild cardiac dysfunction can persist. (29128863)
- Probably results from severe catecholamine surges affecting the myocardium.
- Epinephrine may have the greatest effect in apical regions of the heart where beta-adrenoreceptor density is highest. (31994355)
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- Failure to recognize LV outflow tract obstruction in patients with apical hypokinesis. (LV outflow tract obstruction has major implications for hemodynamic management.)
- Diagnostic confusion between Takotsubo cardiomyopathy versus occlusive MI. These entities can look nearly identical on ECG and echocardiography, so when in doubt consult with cardiology and consider catheterization.
- Premature prognostication of cardiac function in patients with Takotsubo cardiomyopathy (the ejection fraction may look awful, but patients can still have a dramatic recovery).
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References
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- 20510222 Kosuge M, Ebina T, Hibi K, et al. Simple and accurate electrocardiographic criteria to differentiate takotsubo cardiomyopathy from anterior acute myocardial infarction. J Am Coll Cardiol. 2010;55(22):2514-2516. doi:10.1016/j.jacc.2009.12.059 [PubMed]
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- 29627435 Jesel L, Berthon C, Messas N, Lim HS, Girardey M, Marzak H, Marchandot B, Trinh A, Ohlmann P, Morel O. Ventricular arrhythmias and sudden cardiac arrest in Takotsubo cardiomyopathy: Incidence, predictive factors, and clinical implications. Heart Rhythm. 2018 Aug;15(8):1171-1178. doi: 10.1016/j.hrthm.2018.04.002 [PubMed]
- 31994355 Keramida K, Backs J, Bossone E, Citro R, Dawson D, Omerovic E, Parodi G, Schneider B, Ghadri JR, Van Laake LW, Lyon AR. Takotsubo syndrome in Heart Failure and World Congress on Acute Heart Failure 2019: highlights from the experts. ESC Heart Fail. 2020 Apr;7(2):400-406. doi: 10.1002/ehf2.12603 [PubMed]
- 32042529 Sattar Y, Siew KSW, Connerney M, Ullah W, Alraies MC. Management of Takotsubo Syndrome: A Comprehensive Review. Cureus. 2020 Jan 3;12(1):e6556. doi: 10.7759/cureus.6556 [PubMed]
- 32469155 Chioncel O, Parissis J, Mebazaa A, Thiele H, Desch S, Bauersachs J, Harjola VP, Antohi EL, Arrigo M, Gal TB, Celutkiene J, Collins SP, DeBacker D, Iliescu VA, Jankowska E, Jaarsma T, Keramida K, Lainscak M, Lund LH, Lyon AR, Masip J, Metra M, Miro O, Mortara A, Mueller C, Mullens W, Nikolaou M, Piepoli M, Price S, Rosano G, Vieillard-Baron A, Weinstein JM, Anker SD, Filippatos G, Ruschitzka F, Coats AJS, Seferovic P. Epidemiology, pathophysiology and contemporary management of cardiogenic shock – a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2020 Aug;22(8):1315-1341. doi: 10.1002/ejhf.1922 [PubMed]
- 32568589 Crinion D, Abdollah H, Baranchuk A. An Ominous ECG Sign in Critical Care. Circulation. 2020 Jun 23;141(25):2106-2109. doi: 10.1161/CIRCULATIONAHA.120.047427 [PubMed]
- 34362020 Di Vece D, Silverio A, Bellino M, Galasso G, Vecchione C, La Canna G, Citro R. Dynamic Left Intraventricular Obstruction Phenotype in Takotsubo Syndrome. J Clin Med. 2021 Jul 22;10(15):3235. doi: 10.3390/jcm10153235 [PubMed]
- 35002350 Assad J, Femia G, Pender P, Badie T, Rajaratnam R. Takotsubo Syndrome: A Review of Presentation, Diagnosis and Management. Clin Med Insights Cardiol. 2022 Jan 4;16:11795468211065782. doi: 10.1177/11795468211065782 [PubMed]
- 35344411 Singh T, Khan H, Gamble DT, Scally C, Newby DE, Dawson D. Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications. Circulation. 2022 Mar 29;145(13):1002-1019. doi: 10.1161/CIRCULATIONAHA.121.055854 [PubMed]