Takotsubo Cardiomyopathy


Article Author:
Sarah Ahmad
Daniel Brito
Nauman Khalid


Article Editor:
Michael Ibrahim


Editors In Chief:
Michael Firstenberg
Lawrence Greiten


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
6/22/2019 8:14:06 AM

Introduction

Takotsubo cardiomyopathy also known as transient apical ballooning syndrome, apical ballooning cardiomyopathy, stress-induced cardiomyopathy, stress cardiomyopathy, Gebrochenes-Herz syndrome, and the broken-heart syndrome is a form of non-ischemic cardiomyopathy [1][2][3][4][5][6] and predominantly affects post-menopausal women [7][8]. It is characterized by transient regional systolic dysfunction of the left ventricle in the absence of angiographically significant coronary artery disease or acute plaque rupture. In most cases of Takotsubo cardiomyopathy, the regional wall motion abnormality extends beyond the territory perfused by a single epicardial coronary artery. The term Takotsubo is a Japanese name for an octopus trap. It has a shape that is similar to the systolic apical ballooning appearance of the left ventricle.

Etiology

The exact etiology of Takotsubo cardiomyopathy is not fully understood. There are several mechanisms hypothesized as possible etiologies of Takotsubo cardiomyopathy and include sympathetic overdrive with increased catecholamines, coronary spasm, microvascular dysfunction, low estrogen levels, inflammation, or impaired myocardial fatty acid metabolism. Risk factors for the development of Takotsubo cardiomyopathy include domestic abuse, death of relatives, natural calamities, accident or major trauma, arguments, financial or gambling loss, diagnosis of an acute medical illness, stimulant drugs such as cocaine, amphetamines or even positive life events the so-called ’happy heart syndrome’.

Epidemiology

The real incidence of Takotsubo cardiomyopathy is uncertain. It makes up for 1 to 2% of patients suspected of having acute coronary syndrome [9][10][11]. One registry of 3265 patients with troponin positive acute coronary syndrome, reported the prevalence of 1.2% [9] of Takotsubo cardiomyopathy whereas a systematic review of patients presenting with suspected acute myocardial infarction the prevalence was reported to be 1.7 to 2.2% [10]. There is a strong predilection of TC to afflict post-menopausal women however males may have a worse prognosis if affected. In the International Takotsubo Registry study (a consortium of multiple centers across Europe and America of 1750 patients) approximately 88.9% of the affected patients were females and the mean age was 66.4 years [12].

Pathophysiology

The precise pathophysiologic mechanism underlying Takotsubo cardiomyopathy remains elusive. Various hypotheses have been postulated and include elevated levels of circulating plasma catecholamines and its circulating metabolites due to underlying stress, microvascular dysfunction or microcirculatory disorder, inflammation, estrogen deficiency, spasm of the epicardial coronary vessels, and aborted myocardial infarction [13][14]. Catecholamine hypothesis is the most widely accepted pathophysiologic mechanism of TC and elevated levels (two to threefold elevation) of plasma catecholamines and neuropeptides (norepinephrine, epinephrine, and dopamine) have been observed in patients with TC. Catecholamines can cause microvascular spasm, dysfunction, myocardial stunning or direct myocardial injury. Estrogen exerts protective effects on cardiovascular system including vasodilation, protection against atherosclerosis and endothelial dysfunction. Therefore post-menopausal women exhibit exaggerated vasoconstriction, altered endothelium-dependent vasodilatation, and sympathetic activation in response to psychosocial stress [15]. The role of inflammation in Takotsubo cardiomyopathy is depicted by cardiac magnetic resonance imaging which shows myocardial edema, necrosis, fibrosis, and late gadolinium enhancement [16]. Coexisting cases of myocarditis, pericarditis, or autoimmune conditions such as systemic lupus erythematosus or Sjogren’s syndrome have been described in the literature suggesting that chronic inflammatory conditions with acute flares may provide a substrate for the emergence of Takotsubo cardiomyopathy[17][18][19]. Microvascular dysfunction is demonstrated by abnormal coronary flow reserve, thrombolysis in myocardial infarction (TIMI) frame count, TIMI perfusion grade and quantitative flow ratio [20][21][22][23][24]. An impaired microvascular function has also been demonstrated with measuring the index of microvascular resistance by introducing a pressure wire in the coronary arteries [25]. There is some evidence that the prevalence of diabetes mellitus is low in Takotsubo cardiomyopathy patients suggesting that blunting of autonomic response in diabetes may have a protective effect against the development of Takotsubo cardiomyopathy the so-called "Diabetes Paradox" [26][27][28].

Histopathology

Endomyocardial biopsy of patients with Takotsubo cardiomyopathy demonstrates reversible focal lysis of myocytes, mononuclear infiltrates, and contraction band necrosis.

History and Physical

Takotsubo cardiomyopathy presentation is similar to the acute coronary syndrome. This disorder is frequently triggered by intense emotional or physical stress, for example, the unexpected death of a family member, domestic abuse, significant confrontation, medical diagnosis, natural disaster, and/or financial loss. In the International Takotsubo Registry study, most common symptoms are chest pain, dyspnea, and syncope. Some patients may present with symptoms and signs of heart failure, tachyarrhythmias, bradyarrhythmias, sudden cardiac arrest, or severe mitral regurgitation. On auscultation, there may be a late-peaking systolic murmur due to left ventricular outflow tract obstruction. There also may be symptoms and signs of transient ischemic attack or stroke-like presentation due to embolization from apical thrombus. Approximately, 10% of patients with stress cardiomyopathy develop cardiogenic shock.

Evaluation

The diagnosis of stress cardiomyopathy should be suspected in adults (particularly postmenopausal women) who present with a suspected acute coronary particularly when the clinical manifestations and electrocardiographic abnormalities are out of proportion to the degree of elevation in cardiac biomarkers. It is important to emphasize that because of the indistinguishable features with the acute coronary disease, Takotsubo cardiomyopathy is a diagnosis of exclusion which can only be made after coronary angiography [29][30][31]. There are several diagnostic criteria proposed for the diagnosis of Takotsubo cardiomyopathy including the Mayo Clinic criteria, the International Takotsubo Diagnostic Criteria (InterTAK Diagnostic Criteria) [32]and others. 

The most widely accepted criteria are the Mayo Clinic diagnostic criteria for identification of stress cardiomyopathy. Outlined below are the key features; all are required to meet the diagnosis [33][34]:

  1. Transient hypokinesis, akinesis, or dyskinesis in the left ventricular mid segments with or without apical involvement; regional wall motion abnormalities that extend beyond.
  2. A single epicardial vascular distribution; and frequently, but not always, a stressful trigger.
  3. The absence of obstructive coronary disease or angiographic evidence of acute plaque rupture.
  4. New ECG abnormalities (ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin.
  5. The absence of pheochromocytoma and myocarditis.

Electrocardiographic findings Patients with TC often exhibit a dynamic pattern of electrocardiographic (ECG) changes akin to the ECG staging in pericarditis [35]. ST-segment elevation develops in stage 1 followed by normalization of the ST segment in stage 2. T wave inversions develop in stage 3 whereas complete normalization of T waves or very rarely persistence of T wave inversions occur in stage 4. There may be some overlap in stages 2 and 3 and all patients may not exhibit all stages.

Laboratory findings Cardiac biomarkers including troponins and CK-MB show mild elevation. According to the International, Takotsubo Registry study, the median initial troponin was 7.7 times the upper limit of normal. Levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP are elevated in most patients with stress cardiomyopathy and exceeded those seen in a matched cohort of patients with the acute coronary syndrome (median 5.89 versus 2.91 times the upper limit of normal) [12].

Transthoracic echocardiography demonstrates the wall motion abnormalities classified as:

  • Apical type (typical): there is a systolic apical ballooning of the left ventricle, with depressed mid and apical segments, and also hyperkinesis of the basal walls. This variant was found in approximately 80% of patient in the International Takotsubo Registry study [12].
  • Atypical variants: Mid-ventricular type hypokinesis (14.6%), basal type hypokinesis (2.2%), focal type hypokinesis (most commonly the anterolateral segment) (1.5%) and global hypokinesis [12].

Most patients with stress cardiomyopathy have reduced overall left ventricular systolic function, and right ventricular dysfunction has been reported too.

Cardiovascular magnetic resonance imaging may be helpful in the diagnosis and evaluation of stress cardiomyopathy, particularly when the echocardiogram is suboptimal, or there is coexistent coronary artery disease. Cardiovascular magnetic resonance may assist in the differential diagnosis, delineate the full extent of ventricular abnormalities, and identify associated complications. It may also demonstrate myocardial edema, necrosis, fibrosis, and occasionally late gadolinium enhancement.

Radionuclide myocardial perfusion imaging is not indicated in most patients presenting with Takotsubo cardiomyopathy since most of the common presentation is acute coronary syndrome requiring cardiac catheterization. In a low to intermediate risk non-ST elevation acute coronary syndrome, radionuclide myocardial perfusion imaging may be helpful.

Cardiac catheterization is an invasive procedure of choice when Takotsubo cardiomyopathy present as ST-elevation acute coronary syndrome or troponin positive acute coronary syndrome. Coronary angiography will show normal coronary anatomy or mild to moderate coronary atherosclerosis.

Treatment / Management

Although Takotsubo cardiomyopathy is thought to be a benign condition the recent observation data suggest that the rates of cardiogenic shock and death are comparable to patients with the acute coronary syndrome. Thus initial management should focus on identifying and close monitoring of patients at risk for serious complications. Predictors of adverse in-hospital outcomes include: physical trigger, acute neurologic or psychiatric diseases, initial troponin greater than 10× upper reference limit, and admission left ventricular ejection fraction less than 45% [12]. Male patients have up to three-fold increased rate of death and major adverse cardiac and cerebrovascular events primarily due to an increased burden of comorbidities [36]. Guidelines on the management of Takotusbo cardiomyopathy are lacking as there are no prospective randomized data in this regard, thus management is based on clinical experience and expert consensus (evidence level C). Since the initial presentation of Takotsubo cardiomyopathy is similar to an acute coronary syndrome, the initial treatment involves aspirin, beta blocker, ACE inhibitor, a lipid-lowering agent, and coronary angiography to rule out obstructive coronary artery disease [37]. The therapy is guided by the patient’s clinical presentation and hemodynamic status. In stable patients, treatment modalities include cardioselective beta-blockers and ACE inhibitor for a short period around 3-6 months, with serial imaging studies to determine wall motion abnormalities and ventricular ejection fraction to determine progression or improvement. Anticoagulation is usually reserved for those with documented ventricular thrombus or evidence of embolic events; that occurs in 5% of patient with Takotsubo cardiomyopathy. In a patient with more unstable hemodynamics, or those who present in cardiogenic shock, and in the absence of left ventricular outflow obstruction, should be treated with inotropes. Alternatively, patients may derive further benefit from mechanical hemodynamic support with an intra-aortic balloon pump or rarely, left ventricular assist devices. If left ventricular outflow obstruction is present with cardiogenic shock, inotropes should be avoided, and phenylephrine is the pressor agent of choice often combined with beta-blocker agents.

Differential Diagnosis

The main differentials to consider include acute coronary syndrome, cocaine-related coronary syndrome, coronary artery spasm, esophageal spasm, myocarditis, pericarditis, and pheochromocytoma.

Prognosis

Although most patients with Takotsubo cardiomyopathy recover the risk of complications among hospitalized patients is similar to that of acute myocardial infarction. The reported mortality among patients with Takotsubo cardiomyopathy ranges from 0 to 8% [34][38][39][40][12] with a mortality of 4.1% in the International Takotsubo Registry study [12]. Prognosis of Takotsubo cardiomyopathy depends upon its underlying trigger and TC should be subclassified into primary and secondary forms. Primary TC occurs due to emotional/psychological stimuli and secondary forms occur due to physical factors in hospitalized setting such as sepsis, trauma, surgery or other critical illnesses. Secondary TC is associated with worse in-hospital and long-term outcomes [41][42][43]. Despite the low prevalence of Takotsubo cardiomyopathy in males they often have a worse prognosis. This can possibly be explained by the fact that males possess a higher prevalence of acute critical illnesses with elevated circulating catecholamines which may result in higher in-hospital mortality [8]

Complications

The main complications include left ventricular outflow tract obstruction, life-threatening ventricular arrhythmias, paroxysmal or persistent atrial fibrillation, hypotension, low output syndrome, cardiogenic shock, heart failure, and thromboembolism. The incidence of the second event in patients who survive the initial event is about 5% and mostly occurring 3 weeks to 3.8 years after the first event [44].

Enhancing Healthcare Team Outcomes

The diagnosis and management of anginal pain are with a multidisciplinary team that consists of the primary care provider, nurse practitioner, cardiologist, radiologist, and pharmacist. When patients with chest pain are encountered, healthcare workers should consider Takotsubo cardiomyopathy in the differential diagnosis. Since the initial presentation of Takotsubo cardiomyopathy mimics acute coronary syndrome, initial treatment involves aspirin, beta blocker, ACE inhibitor, a lipid-lowering agent, and coronary angiography to rule out obstructive coronary artery disease. Takotsubo cardiomyopathy is a temporary condition, and hence the goals of treatment are usually conservative and supportive care. The therapy is guided by the patient’s clinical presentation and hemodynamic status. In stable patients, treatment modalities include cardioselective beta-blockers and ACE inhibitor for a short period around 3-6 months, with serial imaging studies to determine wall motion abnormalities and ventricular ejection fraction to determine progression or improvement. Anticoagulation is usually reserved for those with documented ventricular thrombus or evidence of embolic events; that occurs in 5% of patient with Takotsubo cardiomyopathy. The outlook in most patients with treatment is excellent with the chest pain resolving in a matter of weeks. 


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Takotsubo Cardiomyopathy - Questions

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A 69-year-old female presents to the emergency department with symptoms of chest pain and dyspnea. At nine o'clock in the morning, she received a phone call regarding her son suffering a head injury during the line of duty. One hour later, she developed substernal chest pain with radiation to her jaw. She takes no medications. On physical examination, temp is 98.1 F, blood pressure is 140/90 mmHg, pulse is 90 beats/min, and respiratory rate is 18. Her body mass index is 24. Carotid upstroke is normal with no bruit. Jugular venous pulsation is normal. S1 and S2 are normal without murmur, gallops, or rubs. Electrocardiogram shows normal sinus rhythm at 100 beats/min and 1 mm ST segment elevation in leads V1-V4. There are no Q waves. Serum troponin is 2 ng/ml. An echocardiogram shows reduced wall motion of the anterior and apical portion of the heart, hyperdynamic wall motion of the basal segment, no pericardial effusion, and no significant valvular heart disease. Emergent coronary angiography shows normal coronary anatomy. Left ventriculography shows an akinetic apex and a hyperdynamic basal segment of the heart. What is the most likely diagnosis?



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What also is known as Gebroachenes-Herz syndrome?



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A 75-year-old male with a past medical history of diabetes mellitus type 2, hypertension, peripheral vascular disease, hypothyroidism, and rheumatoid arthritis presents with significant substernal chest pain and diaphoresis after acute emotional stress. His electrocardiogram reveals anterior ST-segment elevations. His cardiac troponin levels are slightly elevated. A coronary angiogram reveals 40% stenosis of the proximal right coronary artery. The left anterior descending artery is wrapped around the apex of the heart. Left ventriculography reveals apical ballooning in the mid, distal, and apical segments, and a hypercontractile basal segment. What is the treatment for this disorder?



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What is the most common ECG finding in broken heart syndrome or Takotsubo cardiomyopathy?



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In which group is Takotsubo cardiomyopathy most common?



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Which is true of Takotsubo cardiomyopathy?



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A 65-year-old female with a past medical history of hypertension presents with significant substernal chest pain after series of emotional stress. Her first electrocardiogram reveals nonspecific changes. Her cardiac troponin levels were slightly elevated. A coronary angiogram reveals 40% stenosis of the mid left anterior descending artery. Left ventriculography done in right anterior oblique (RAO) projection revealed mid ballooning in the left ventricular (LV) anterior and inferior walls and a hypercontractile basal segment. Left ventricular end-diastolic pressure (LVEDP) was 15 mmHg. What is the treatment for this disorder?



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Which ECG finding is uncommon in patients with Takotsubo cardiomyopathy (TTC)?



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A 70-year-old man undergoes surgical resection for prostate cancer. During the early postoperative course, he develops hypotension and congestive heart failure requiring intubation. His echocardiogram demonstrates akinesis of the basal segment and hyperkinesis of the apical segment. Which of the following forms of cardiomyopathy does he most likely have?



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A 65-year-old woman with no previous history of cardiac disease presents with severe chest pain and dyspnea over the past 24 hours. Initial 12-lead electrocardiogram demonstrates ST-segment elevation in the precordial leads, and she is taken emergently to the cardiac catheterization laboratory. Coronary angiography demonstrates only mild epicardial coronary artery disease. Echocardiography is performed and demonstrates significant apical and midventricular akinesis. Which of the following complications has the highest risk of occurring in this patient?



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A 60-year-old woman with no previous history of cardiac disease presents with severe chest pain and dyspnea, which developed after a heated argument with her husband. Initial 12-lead electrocardiogram demonstrates ST-segment elevation in the precordial leads. She is taken emergently to the cardiac catheterization laboratory. Coronary angiography demonstrates mild epicardial coronary artery disease. Echocardiography shows significant apical akinesis with a mural left ventricular (LV) apical thrombus. Which of the following is the most appropriate initial treatment for this patient?



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A 50-year-old woman survives a near-drowning episode. She is brought to the emergency department. Initial 12-lead electrocardiogram demonstrates T-wave inversions in the precordial leads. Her blood pressure is 70/40 mmHg, and the heart rate is 112/minute. Emergency coronary angiography demonstrates no evidence of epicardial coronary artery disease. Left ventriculography shows basal hyperkinesis with apical akinesis. She is admitted to the coronary care unit, given her significant hypotension and tachycardia. Which of the following vasopressors is most appropriate for this patient?



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Takotsubo Cardiomyopathy - References

References

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Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Surgery-Cardiac. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Surgery-Cardiac, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Surgery-Cardiac, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Surgery-Cardiac. When it is time for the Surgery-Cardiac board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Surgery-Cardiac.