Takotsubo Syndrome

Acute, usually reversible left ventricular systolic dysfunction with regional wall motion abnormality extending beyond one coronary territory (classically apical ballooning with basal hyperkinesis), triggered by emotional or physical stress, without a culprit obstructive coronary lesion.

• It accounts for about 1 to 3% of suspected acute coronary syndromes (5 to 6% in women with suspected infarction). About 90% of patients are women, mostly postmenopausal, with a mean age of about 66 to 70 years.
• Mechanism: catecholamine surge, coronary microvascular dysfunction and direct myocyte toxicity, with a brain heart axis.
• Triggers: emotional (bereavement, conflict) and physical (surgery, sepsis, stroke, subarachnoid haemorrhage, seizure, acute respiratory failure, phaeochromocytoma, exacerbation of asthma), drugs (adrenaline, dobutamine, venlafaxine, excess thyroxine), and none identified in about 30%.
• Patterns: apical (about 80%), midventricular (about 15%), basal or inverted (2 to 5%), focal; right ventricular involvement in about 25%.
• Outcome is less benign than once thought: in hospital mortality is about 4 to 5% (higher in men and with physical triggers), and complications occur in about 20%. Recurrence is about 1 to 4% per year.

• Chest pain (about 75%), dyspnoea (about 50%), syncope, palpitations, and cardiogenic shock (about 10%).
• Signs: tachycardia, hypotension in severe cases, crackles, systolic murmur from left ventricular outflow tract obstruction (about 10 to 25%) or mitral regurgitation.
• Differential diagnosis: ST elevation and non-ST elevation myocardial infarction, myocarditis, coronary vasospasm, spontaneous coronary artery dissection, aortic dissection, pulmonary embolism, phaeochromocytoma crisis, sepsis cardiomyopathy, and stroke related cardiac dysfunction.
• Complications: cardiogenic shock, acute heart failure and pulmonary oedema, ventricular tachycardia and fibrillation (about 4 to 5%), atrial fibrillation (5 to 15%), bradycardia and QT prolongation with torsades, left ventricular outflow tract obstruction, mitral regurgitation, left ventricular thrombus (2 to 5%), and rarely free wall rupture (less than 1%).

• ECG: ST elevation in about 40 to 45% (usually anterior and without reciprocal depression), ST depression, then deep T wave inversion with QT prolongation over days 1 to 3.
• Troponin is usually modestly raised and disproportionately low for the degree of dysfunction; natriuretic peptide is markedly raised.
• Echocardiography: apical ballooning with basal hyperkinesis (or midventricular, basal or focal variants), ejection fraction usually 20 to 49%, left ventricular outflow obstruction with gradient greater than 30 mmHg, mitral regurgitation, thrombus.
• Coronary angiography with left ventriculography: no culprit lesion (obstructive coronary disease coexists in about 15% and does not exclude the diagnosis).
• Cardiac MRI: myocardial oedema without or with minimal late gadolinium enhancement, and exclusion of myocarditis.
• Recovery of ventricular function on repeat echocardiography within 1 to 8 weeks supports the diagnosis; if function does not recover, reconsider myocarditis, infarction, or cardiomyopathy.
• Look for a trigger: thyroid function, glucose, infection screen, head imaging if neurological, plasma or urine metanephrines if hypertensive crisis and paroxysms, and drug review.

• Initial care: until angiography excludes obstructive disease, give aspirin 300 mg once and enoxaparin 1 mg/kg SC (or unfractionated heparin); stop both unless coronary disease is present. Telemetry for at least 48 to 72 hours.
• Uncomplicated disease:
  • Ramipril 2.5 mg daily titrated to 10 mg (or an ARB such as valsartan 40 to 160 mg twice daily if cough), continued until function recovers; it may reduce recurrence (evidence is limited).
  • Bisoprolol 2.5 to 5 mg daily after stabilisation if there is no shock, bradycardia, conduction disease or left ventricular outflow obstruction (benefit for recurrence is not proven).
  • Furosemide 20 to 40 mg IV for pulmonary congestion, used with caution if outflow obstruction is present.
• Left ventricular outflow tract obstruction:
  • Stop catecholamines, nitrates, diuretics and inotropes.
  • Give 250 to 500 mL of 0.9% saline if hypovolaemic.
  • Give esmolol 0.5 mg/kg IV then 50 to 300 micrograms/kg/min (or metoprolol 2.5 to 5 mg IV), and phenylephrine 20 to 100 micrograms/min to raise afterload.
  • Avoid intra aortic balloon pump.
• Cardiogenic shock without outflow obstruction:
  • Avoid adrenaline, dobutamine and dopamine, which can worsen the syndrome.
  • Use levosimendan 0.05 to 0.2 micrograms/kg/min (evidence is limited) and mechanical support (venoarterial ECMO, percutaneous ventricular assist device, intra aortic balloon pump).
• Left ventricular thrombus prevention and treatment: enoxaparin 1 mg/kg SC twice daily then warfarin to INR 2.0 to 3.0 for 3 months (or until recovery of apical wall motion) in patients with apical akinesis and ejection fraction less than 30% or documented thrombus; evidence is limited.
• Arrhythmia:
  • Torsades or marked QT prolongation: magnesium sulfate 2 g IV over 10 minutes, potassium to 4.5 mmol/L or more, stop QT-prolonging drugs, and temporary pacing for bradycardia dependent torsades.
  • Ventricular tachycardia or fibrillation in the acute phase: cardioversion or defibrillation, and a wearable defibrillator rather than an implanted device because the dysfunction is usually reversible.
  • Atrial fibrillation: rate control with low dose bisoprolol; anticoagulate if it persists.
• Treat the trigger: alpha blockade for phaeochromocytoma, treatment of sepsis, respiratory support, review of drugs (stop venlafaxine or excess thyroxine).
• Psychological support: counselling and treatment of anxiety and depression.
• Special groups:
  • Men: higher mortality and more physical triggers; look for a physical cause.
  • Pregnancy: rare, usually peripartum; stop ACE inhibitors and ARBs; use metoprolol with caution; involve obstetric and cardiology teams.
  • Children: rare; treat the trigger and give supportive care.
  • Elderly: manage fluids and arrhythmia carefully; higher complication rates.
• Red flags: hypotension, pulmonary oedema, sustained ventricular arrhythmia, new murmur (outflow obstruction, mitral regurgitation), thrombus, failure of recovery.
• Follow up: repeat echocardiography at 4 to 8 weeks to confirm recovery; review at 3 and 12 months; continue ramipril until recovery; counsel about stress and about recurrence.