Takotsubo Cardiomyopathy

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 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 (most common)
• Dyspnea
• Syncope
• Palpitations
• Fatigue
• Dizziness
• Nausea 

Physical exam

• May be nonspecific
• Hypotension → cardiogenic shock
• Hypoxia → pulmonary edema
• Tachyarrhythmias or bradyarrhythmias
• Diaphoresis
• Crackles → pulmonary edema
• Late-peaking systolic murmur → mitral regurgitation and left ventricular outflow tract obstruction

Diagnosis

Diagnostic algorithm

Because patients present similar to ACS, the diagnostic process will be similar.

Diagnostic evaluation

Initial testing:

• Electrocardiogram (ECG)
  • ST-segment elevations, usually in the precordial leads
  • ST-segment depressions
  • QT prolongation
  • T-wave inversions
• Troponin
  • ↑ in most cases
• Brain natriuretic peptide (BNP)
  • ↑ in most cases, but not required for diagnosis

Next steps:

• Cardiac catheterization
  • Often done emergently to rule out ACS
  • No critical coronary artery disease will usually be found.
  • Left ventriculogram will show apical ballooning.
    • Contrast dye is injected into the left ventricle to visualize systolic function.
• Echocardiography
  • Should be done in all patients with suspected takotsubo cardiomyopathy
  • Demonstrates regional wall-motion abnormalities and systolic dysfunction: 
    • Mid and apical hypokinesis of the left ventricle
    • Left ventricular apical ballooning
    • ↓ left ventricular ejection fraction (LVEF)
    • Abnormalities will not follow a vascular distribution.
  • May reveal LVOT obstruction 
  • Evaluates for a thrombus in the ventricle
• Cardiovascular magnetic resonance imaging (cMRI) 
  • Used if echocardiography is suboptimal
  • Myocardial edema is usually seen.
  • May pick up a thrombus in the ventricle
  • Can differentiate takotsubo cardiomyopathy from myocarditis
  • Other findings will be similar to those seen with echocardiography.

Diagnostic criteria

The following 4 criteria are required for diagnosis:

• Transient left ventricular systolic dysfunction (hypokinesis, akinesis, or dyskinesis) observed on echocardiogram
• Absence of obstructive coronary disease or acute plaque rupture observed on coronary angiography
• New electrocardiogram abnormalities observed on ECG or modest elevation in cardiac troponin
• Absence of pheochromocytoma or myocarditis

Management

Management

• 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
  • 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.
  • 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. Symptoms include substernal chest pain, dyspnea, and diaphoresis. The diagnosis is made from 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, 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 of the heart muscle with an infectious or non-infectious etiology. Presentation varies but can include heart failure and cardiogenic shock. Echocardiogram may show global systolic dysfunction, cMRI will show 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 activity and vasospasm. Symptoms include chest pain and dyspnea. An 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: an excess of thyroid hormones, which may result in heart failure over time. Symptoms include tachycardia, palpitations, dyspnea, angina, and 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.