Takotsubo cardiomyopathy

Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy, refers to acute, stress-induced, reversible dysfunction of the left ventricle. It is an uncommon but clinically significant cause of chest pain that can mimic acute coronary syndrome (ACS). Typically triggered by an extreme emotional stressor or severe illness, it is typically characterized by ballooning of the left ventricular wall, which can lead to chest pain and heart failure. While most cases fully resolve within a couple of weeks, patients can become critically ill, particularly if the disease causes left ventricular outflow tract obstruction (LVOT obstruction). As symptoms overlap with those seen in acute coronary syndrome, this condition should be excluded. See also cardiomyopathy for information on other cardiomyopathies.

• Definition: : acute, stress-induced; , reversible dysfunction of the left ventricle that can mimic acute coronary syndrome
• Classification ^[1]
  • Primary form: Symptoms have led the patient to seek medical attention.
  • Secondary form : The patient is already seriously ill with another condition, meaning that the presentation may be more insidious.

• 90% of affected individuals are postmenopausal women. ^[2]
• More common in patients with preexisting mental illness ^[3]

Epidemiological data refers to the US, unless otherwise specified.

• Triggers ^[2][3]
  • Intense emotional stress
    • The stress is usually negative (i.e., “broken heart syndrome”)
    • Less common: strong, positive emotions (i.e., “happy heart syndrome”)
  • Severe illness
  • Drugs
• Pathophysiology: Emotional/physical stress → activation of the sympathetic nervous system; → massive catecholamine discharge; → cardiotoxicity, multivessel spasms, and dysfunction → myocardial stunning

Symptoms overlap with those seen in acute coronary syndrome (see “Clinical features” in acute coronary syndrome) and are characteristically preceded by a stressful event. ^[1][2]

• Most common symptoms
  • Retrosternal chest pain with typical features of angina
  • Dyspnea
• Additional symptoms
  • Syncope
  • Arrhythmias
  • Signs of heart failure and/or cardiogenic shock (e.g., hypotension, pulmonary edema)

The diagnosis of takotsubo cardiomyopathy requires left ventricle regional wall motion abnormalities (typically reversible) that extend beyond a single coronary artery distribution in the absence of obstructive coronary artery disease. It is extremely difficult to distinguish between takotsubo cardiomyopathy and acute coronary syndrome (ACS) on the basis of ECG and laboratory test findings alone; emergency coronary angiography is usually required to rule out ACS. ^[1][2]

Approach

• Check ECG, cardiac biomarkers, and bedside TTE (if available).
• Determine the pretest probability of takotsubo cardiomyopathy and ACS (using patient risk factors and diagnostic criteria).
  • If pretest probability for ACS is high, perform emergent coronary angiography.
  • If pretest probability for ACS is low, consider noninvasive imaging methods (e.g., TTE).
• Check cardiac MRI to better characterize myocardial edema.

Diagnostic criteria

Several diagnostic criteria are used to establish a diagnosis of stress-induced cardiomyopathy, including the revised Mayo Clinic criteria and the InterTAK diagnostic score.

• Revised Mayo Clinic criteria: all of the following must be present ^[1][4]
  • Presence of cardiac ischemia
    • New ECG abnormalities: ST-segment elevation and/or T-wave inversions
    • Elevation in serum troponin
  • Presence of LV dysfunction (with or without apical involvement)
    • Transient hypokinesis, dyskinesis, or akinesis of the left ventricular midsegments
    • Wall motion abnormalities extend past a single coronary artery vascular distribution.
    • A stressful trigger is often present.
  • Absence of obstructive coronary disease or acute plaque rupture (typically requires angiography)
  • Absence of myocarditis or pheochromocytoma

Laboratory studies ^[1][2]

• ↑ Troponin T/I
• ↑ Creatine kinase-MB
• ↑ BNP

ECG ^[2]

ECG is abnormal in > 95% of patients with takotsubo cardiomyopathy and usually shows ischemic changes. ^[1]

• ST elevations (most common finding), typically in the precordial leads
  • ST elevation in aVR, in combination with ST elevations in V1–V3, is 100% specific for stress cardiomyopathy versus ACS. ^[1]
• ST depressions are uncommon (< 10% of cases).
• Diffuse T-wave inversions
• Prolonged QT interval

Imaging

• Echocardiography (TTE) ^[6]
  • Indications: all patients suspected of having takotsubo cardiomyopathy
  • Supportive findings
    • ↓ LVEF
    • Global LV dyskinesis involving the apex (most common)
    • Regional wall motion abnormalities
      • Apical left ventricular ballooning (not always present)
      • More rarely, midventricular ballooning (10–20% of cases) or basal ballooning (< 5% of cases) may be present ^[1]
    • LVOT obstruction may be present (up to 25% of cases) ^[1]
• Coronary angiography (with ventriculography) ^[2]
  • Indications: to exclude ACS
  • Findings
    • Most cases: normal coronary arteries or nonobstructive coronary artery disease
    • ∼ 15% of cases: obstructive coronary artery disease may also be present
• Cardiac MRI ^[1][7][8]
  • Indications
    • To exclude differential diagnoses (e.g., myocarditis) and confirm the diagnosis of takotsubo cardiomyopathy in stable patients
    • Allows for better imaging of the right ventricle
  • Suggestive findings
    • Similar to findings in TTE
    • Transmural edema along the areas of wall motion abnormalities
    • Myocardial scarring
  • Possible additional findings
    • LVOT obstruction
    • Valve disease
    • Pericardial effusion
    • LV thrombus
• Coronary CT angiography: consider as an alternative for stable patients with contraindications to cMRI to exclude high-grade coronary stenosis ^[1]

• Acute coronary syndrome
• Acute myocarditis
• See differential diagnosis of chest pain.
• See cardiomyopathy.

The differential diagnoses listed here are not exhaustive.

Treatment is mostly symptomatic and consists of supportive care and treatment of complications and comorbidities (e.g., acute heart failure, arrhythmias). It is critical to determine if LVOT obstruction (which is typically accompanied by mitral regurgitation) is present because inotropic support in these patients can precipitate worsening cardiac function and lead to cardiogenic shock. Consider empiric treatment for acute coronary syndrome until it can be ruled out. All patients should be admitted to the hospital for at least 48 hours of continuous telemetry.

Hemodynamically stable patients ^[1][9]

• Heart failure management ^[1]
  • Treat as systolic heart failure (see “Treatment” in heart failure).
  • ACE inhibitors (e.g., lisinopril )
  • Low-dose beta blockers (e.g., metoprolol tartrate )

Hemodynamically unstable patients ^[1][9]

No LVOT obstruction ^[1]

• Inotropic support: Dobutamine and dopamine can be used; however, both can cause tachycardia and worsening of takotsubo cardiomyopathy, and so other agents, e.g., levosimendan, may be preferable. Patients receiving inotropic support should be monitored closely for the development of LVOT. ^[1]
  • Levosimendan ^[10][11]
  • OR milrinone
• Vasopressor support: if inotropes are insufficient ^[1]
  • Phenylephrine
  • OR vasopressin
• Advanced therapies: consider in refractory cases
  • Intra-aortic balloon pump (IABP)
  • Left ventricular assist device
  • ECMO

LVOT obstruction (occurs in up to 25% of cases) ^[1]

LVOT obstruction further impairs LV systolic function and can be very difficult to treat. Inotropic support should be avoided, as this can precipitate cardiogenic shock in patients with LVOT obstruction.

• IV fluids: may improve LV systolic function
• Beta blocker: Use of a short-acting, low-dose beta blocker (if tolerated) may be helpful to relieve LVOT obstruction but should be used with caution in patients with hypotension. ^[12]
  • Esmolol ^[13]
  • Propranolol ^[14]
  • Metoprolol tartrate ^[15]
• Vasopressor support: in cases of shock
  • Phenylephrine
  • OR vasopressin
• Advanced therapies: consider in refractory cases
  • Left ventricular assist device
  • ECMO
• The following therapies should be avoided:
  • Inotropes
  • Vasodilators
  • Nitroglycerin
  • Diuretics
  • IABP

Avoid inotropes, as they can worsen LVOT obstruction and precipitate cardiogenic shock.

Additional considerations for all patients ^[1][9]

• Empiric treatment of ACS: Consider until ACS is ruled out (see “Treatment” in acute coronary syndrome and “Diagnostic criteria” above).
• VTE prophylaxis: consider especially in patients with reduced apical motion and all unstable patients ^[1]
  • Unfractionated heparin
  • OR low molecular weight heparin (e.g., enoxaparin )
• Prevention of arrhythmia
  • Monitor for at least 48 hours with continuous telemetry.
  • Consider beta-blocker therapy (e.g., metoprolol tartrate ).
• Chronic therapy
  • Most standard heart failure therapies have no known significant benefits for patients with takotsubo cardiomyopathy. ^[1]
  • Consider chronic beta blocker therapy (e.g., metoprolol tartrate ).
  • Consider a chronic ACE inhibitor or ARB (e.g., lisinopril , losartan ). ^[1]
• Identify and treat the underlying cause: e.g., SSRI therapy for depression

Although most patients recover within days to weeks, relapses are not uncommon and in-hospital deaths occur especially in patients with complications leading to cardiogenic shock.

• Recovery: within 1–2 weeks in most cases ^[1]
• Recurrence rate: 2–4% per year ^[1]
• In-hospital mortality: up to 5% ^[1]

All patients

• Evaluate the need for urgent coronary angiography.
  • High pretest probability for ACS: urgent coronary angiography (see the acute management checklist for STEMI)
  • Low pretest probability for ACS: further risk stratification (e.g., using the InterTAK score)
• Check troponin, BNP.
• Cardiology consult
• Echocardiogram and/or cMRI
• VTE prophylaxis
• Continuous telemetry for 48 hours
• Monitor QTc. ^[16]
• Identify and treat the underlying cause.

Hemodynamically stable patients

• Supportive care
• Treat systolic heart failure (e.g., diuresis, low-dose beta blocker, ACE inhibitor/ARB).

Hemodynamically unstable patients

• Transfer to ICU.
• Determine whether there is LVOT obstruction.
  • No LVOT obstruction: Administer inotropes, vasopressor.
  • LVOT obstruction: IV fluids, vasopressor support; consider low-dose beta blocker
• Deteriorating patients: Consider mechanical circulatory support.

• Avoid triggers of physical and/or emotional stress.
• Consider chronic beta blocker and/or ACE inhibitor/ARB therapy. ^[1][9]
• Consider assessment (and referral to treatment) for mental health comorbidities. ^[1]