Overview

Epidemiology

• Postmenopausal women > 60 years of age (up to 90% of cases)
• Caucasian or Asian descent
• 1%–2% of patients presenting with suspected acute coronary syndrome (ACS) are found to have takotsubo cardiomyopathy.
• Incidence among individuals exposed to an emotional or physical stress is not known.

Etiology

The exact cause for this condition is unknown, but it is associated with the following:

• Emotional stressors
  • Loss of a loved one
  • Financial distress
• Physical stressors
  • Domestic abuse and physical assault 
  • Severe medical illness
  • Surgery
  • Drug or alcohol abuse
• Underlying psychiatric or neurologic disorders appear to increase a patient’s risk.

Pathophysiology

• Mechanism is not well understood.
• Postulated pathogenesis: 
  • Stress-induced catecholamine release → direct myocardial toxicity and vascular dysfunction → transient ↓ In left ventricular function (“stunning”) → ↓ contractility → systolic dysfunction and ↓ cardiac output
  • It is not clear why the mid-cavity and apex of the left ventricle are affected.
• Left ventricular outflow tract (LVOT) obstruction can develop due to a compensated hyperkinesis of the left ventricular basal segments.
• Patients may also develop mitral regurgitation Mitral regurgitation Mitral regurgitation (MR) is the backflow of blood from the left ventricle (LV) to the left atrium (LA) during systole. Mitral regurgitation may be acute (myocardial infarction) or chronic (myxomatous degeneration). Acute and decompensated chronic MR can lead to pulmonary venous congestion, resulting in symptoms of dyspnea, orthopnea, and fatigue. Mitral Regurgitation due to involvement of the anterior mitral valve leaflet.

Clinical Presentation

Patients will present similar to those with ACS or heart failure:

Symptoms

• Acute substernal chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain (most common)
• Dyspnea
• Syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope
• Palpitations
• Fatigue
• Dizziness
• Nausea 

Physical exam

• May be nonspecific
• Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension → cardiogenic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock
• Hypoxia → pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema
• Tachyarrhythmias or bradyarrhythmias Bradyarrhythmias Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias
• Diaphoresis
• Crackles → pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema
• Late-peaking systolic murmur → mitral regurgitation Mitral regurgitation Mitral regurgitation (MR) is the backflow of blood from the left ventricle (LV) to the left atrium (LA) during systole. Mitral regurgitation may be acute (myocardial infarction) or chronic (myxomatous degeneration). Acute and decompensated chronic MR can lead to pulmonary venous congestion, resulting in symptoms of dyspnea, orthopnea, and fatigue. Mitral Regurgitation and left ventricular outflow tract obstruction

Management

Treatment

• The acute management prior to diagnosis follows the typical protocol for ACS.
• Management after diagnosis is confirmed:
  • Resolve and prevent stressors.
  • Treat heart failure. 
    • Beta blockers (metoprolol)
    • Angiotensin-converting enzyme (ACE) inhibitors (lisinopril)
    • Diuretics, if evidence of volume overload
  • Consider anticoagulation in patients with an LVEF < 30% to prevent thromboembolism.
  • Follow-up echocardiogram to confirm resolution
    • May discontinue ACE inhibitors once systolic function improves
    • Consider continuing long-term beta-blocker therapy.

Complications

• Cardiogenic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock
  • With LVOT obstruction:
    • Beta blockers
    • Cautious intravenous fluid resuscitation to increase preload
    • Vasopressors (phenylephrine, vasopressin)
    • Avoid inotropic support, as it can worsen LVOT obstruction and shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock.
  • Without LVOT obstruction:
    • Inotropic support (milrinone, dobutamine, dopamine)
    • Vasopressors as a 2nd-line therapy
• Arrhythmias: monitor on telemetry
• Intraventricular thrombus: anticoagulation until LVEF normalizes and thrombus is no longer seen on echocardiogram

Prognosis

• Most patients will have a complete resolution within a couple of weeks.
• In-hospital mortality ranges from 0%‒8%.

Differential Diagnosis

• Myocardial infarction: myocardial damage due to obstructed blood flow in the coronary arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries. Symptoms include substernal chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain, dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, and diaphoresis. The diagnosis is made from ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Normal Electrocardiogram (ECG) changes, elevated troponins, and the demonstration of arterial disease during cardiac catheterization. Treatment includes medical management and revascularization. Cardiac catheterization differentiates this condition from takotsubo cardiomyopathy.
• Pheochromocytoma: a catecholamine-secreting tumor that causes episodic hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, diaphoresis, tachycardia, and headache. Catecholamine excess can induce cardiomyopathy similar to takotsubo cardiomyopathy. Diagnosis is made through measurement of metanephrine and imaging of the tumor, which differentiates the condition from takotsubo cardiomyopathy. Definitive treatment requires surgical removal of the tumor.
• Myocarditis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the heart muscle with an infectious or non-infectious etiology. Presentation varies but can include heart failure and cardiogenic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock. Echocardiogram may show global systolic dysfunction, cMRI will show edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, and endomyocardial biopsy can give a definitive diagnosis. Treatment focuses on management of heart failure and the underlying cause. Echo and cMRI will distinguish this condition from takotsubo cardiomyopathy.
• Cocaine: can induce myocardial ischemia, or infarction, through increased sympathomimetic Sympathomimetic Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (α, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs activity and vasospasm. Symptoms include chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain and dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea. An ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Normal Electrocardiogram (ECG) may show ST-segment changes, and a drug screen will be positive. Treatment is similar to ACS, though beta blockers are not recommended. Cardiac catheterization may be required, which will not show the classic findings of takotsubo cardiomyopathy on the left ventriculogram.
• Hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism: an excess of thyroid hormones Thyroid hormones The 2 primary thyroid hormones are triiodothyronine (T3) and thyroxine (T4). These hormones are synthesized and secreted by the thyroid, and they are responsible for stimulating metabolism in most cells of the body. Their secretion is regulated primarily by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Thyroid Hormones, which may result in heart failure over time. Symptoms include tachycardia, palpitations, dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, angina, and hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension. Diagnosis is made through thyroid function testing and echocardiography, which will differentiate this condition from takotsubo cardiomyopathy. Management includes beta blockers and treatment for hyperthyroidism.