Coronary Artery Aneurysm

A coronary artery aneurysm is a localised dilatation of a coronary segment to at least 1.5 times the diameter of the adjacent normal segment. Diffuse dilatation of this degree is called ectasia. A giant aneurysm exceeds 8 mm, or 4 times the reference diameter.

It is found in about 0.3 to 5% of coronary angiograms. The right coronary artery is involved most often, then the left anterior descending and circumflex arteries. The left main artery is rarely affected.

Atherosclerosis causes about half of adult cases. Kawasaki disease is the leading cause in children and an important cause in young adults. Without treatment 15 to 25% of children with Kawasaki disease develop coronary abnormalities, and about 5% after intravenous immunoglobulin.

Other causes are stent related injury (stent edge or malapposition aneurysm), vasculitis (Takayasu arteritis, polyarteritis nodosa, systemic lupus erythematosus, Behçet disease, IgG4-related disease), connective tissue disease (Marfan and Ehlers-Danlos syndromes), infection (mycotic, syphilitic, tuberculous), trauma, dissection and congenital forms.

Pathophysiology. Loss of elastic lamina and medial integrity, from inflammation, proteolysis or mechanical injury, lets the vessel dilate. Flow slows and becomes turbulent in the sac, so thrombus forms and can embolise to the distal bed.

Ischaemia can also arise from spasm or from stenosis at the neck of the aneurysm. In Kawasaki disease, healing often leaves stenosis at the inlet or outlet. Rupture is rare.

• Most patients are asymptomatic and the aneurysm is found on CT or angiography done for another reason.
• Angina, acute coronary syndrome from thrombosis, embolisation or spasm, ventricular arrhythmia, heart failure and sudden death.
• Rarely: rupture with haemopericardium and tamponade, compression of adjacent structures, fistula and a continuous murmur.
• Features of the cause: childhood fever lasting 5 days or more with conjunctivitis, rash and lymphadenopathy (Kawasaki disease); absent pulses, bruits and systemic symptoms (vasculitis); marfanoid habitus, joint hypermobility or fragile skin (connective tissue disease); fever and a new murmur (infection); previous PCI.

Red flags.

• Acute coronary syndrome or ischaemic ECG change
• Thrombus within the aneurysm or distal embolisation
• Giant aneurysm or rapid enlargement
• Fever with raised inflammatory markers (infected or inflammatory aneurysm)
• Pericardial effusion with falling blood pressure (rupture)
• Ventricular arrhythmia or syncope

• CT coronary angiography. The best test for size, extent, thrombus, wall calcification, relations to adjacent structures and the whole coronary tree. Measure the maximal diameter against the adjacent normal segment.
• Invasive angiography. Shows slow or swirling flow and delayed washout. It underestimates size when the sac contains thrombus. Intravascular ultrasound or optical coherence tomography defines the wall, thrombus and stent malapposition, with caution in giant aneurysms.
• Echocardiography. Images the proximal arteries in children and thin adults. In children use body-surface-adjusted Z scores: under 2 no involvement; 2 to under 2.5 dilatation only; 2.5 to under 5 small aneurysm; 5 to under 10 with an absolute diameter under 8 mm medium; 10 or more, or 8 mm or more, large or giant.
• Cardiac MRI and stress imaging for thrombus, perfusion and scar.
• Adult morphology. Type 1 diffuse ectasia of two or three vessels; type 2 diffuse ectasia of one vessel with localised ectasia of another; type 3 diffuse ectasia of one vessel; type 4 localised or segmental ectasia.
• Cause workup. ESR, CRP, full blood count, antinuclear antibody, ANCA, complement, IgG4, syphilis serology, blood cultures, lipids and glucose. Aortic imaging and genetic testing when vasculitis or connective tissue disease is suspected.

Differential diagnosis.

• Coronary pseudoaneurysm after dissection, PCI or surgery
• Coronary ectasia without focal aneurysm
• Coronary artery fistula and arteriovenous malformation
• Sinus of Valsalva aneurysm
• Left ventricular aneurysm or pseudoaneurysm
• Pericardial cyst, cardiac tumour or mediastinal mass
• Spontaneous coronary artery dissection with a false lumen

No randomised data exist. Treatment follows size, thrombus, ischaemia and cause.

• Risk factor control. Blood pressure under 130/80 mm Hg, no smoking, glucose and weight control, exercise. Atorvastatin 40 to 80 mg orally once daily, with liver enzymes at baseline and 3 months, a lower dose with interacting drugs (clarithromycin, ciclosporin) and avoided in pregnancy, aiming for LDL cholesterol under 1.4 mmol/L (55 mg/dL) and a fall of at least 50%. Add ezetimibe 10 mg once daily when not at target.
• Small or medium aneurysm without thrombus or ischaemia. Aspirin 75 to 100 mg orally once daily long term (usual maximum 325 mg daily).
• Giant aneurysm, thrombus in the sac, thrombotic infarction or very slow flow. Add oral anticoagulation to aspirin. Warfarin 5 mg orally once daily at the start (2 to 3 mg in older adults, liver impairment or interacting drugs), adjusted to an INR of 2.0 to 3.0, no fixed maximum. INR every 2 to 3 days at the start, weekly until stable, then every 4 to 12 weeks. Where warfarin is unsuitable, apixaban 5 mg orally twice daily, reduced to 2.5 mg twice daily when at least two of age 80 years or over, weight 60 kg or under and serum creatinine 133 micromol/L or over are present, also 2.5 mg twice daily at creatinine clearance 15 to 29 mL/min and avoided under 15 mL/min, maximum 10 mg daily, though data are limited. Review the combination at 6 to 12 months because bleeding risk is raised.
• Kawasaki disease, acute illness.
  • Immunoglobulin 2 g/kg intravenously as a single infusion over 10 to 12 hours, ideally within 7 to 10 days of fever onset. Monitor for haemolysis, aseptic meningitis and fluid overload. Delay live vaccines for 11 months.
  • Aspirin 30 to 50 mg/kg/day orally in 4 divided doses (some centres use 80 to 100 mg/kg/day) until afebrile for 48 to 72 hours, then 3 to 5 mg/kg once daily until the coronary arteries are normal at 4 to 6 weeks, and long term when an aneurysm persists. Avoid ibuprofen, which blunts the antiplatelet effect.
  • Fever persisting or recurring 36 hours or more after the infusion ends: second immunoglobulin 2 g/kg, or methylprednisolone 10 to 30 mg/kg intravenously once daily (maximum 1 g) for up to 3 days, or infliximab 5 mg/kg intravenously once, under specialist care.
  • Residual aneurysm by Z score: small, aspirin 3 to 5 mg/kg once daily until regression; medium, long term aspirin with a second antiplatelet considered; large or giant, aspirin plus warfarin to an INR of 2.0 to 3.0, or enoxaparin 1 mg/kg subcutaneously every 12 hours (1.5 mg/kg under 2 months of age) to an anti-Xa level of 0.5 to 1.0 IU/mL taken 4 to 6 hours after the dose.
• Vasculitis. Prednisolone 1 mg/kg orally once daily (maximum 60 mg) with a slow taper and a steroid sparing agent chosen by rheumatology. Add calcium, vitamin D and gastric protection, and screen for tuberculosis and hepatitis B first.
• Infected aneurysm. Intravenous antibiotics chosen by culture for 4 to 6 weeks, with surgical resection and grafting.
• Intervention. Surgery (ligation or resection with bypass grafting) or PCI with a covered stent for symptomatic, enlarging or giant aneurysms with ischaemia or recurrent thrombosis, and for rupture or compression. Bare or drug eluting stents across an aneurysm risk malapposition and thrombosis. Covered stents need prolonged dual antiplatelet therapy.
• Avoid cocaine and other stimulants, and heavy isometric exertion with a giant aneurysm.

Special groups.

• Children with Kawasaki disease: lifelong follow up with planned transition to adult care. Annual inactivated influenza vaccination while on aspirin.
• Pregnancy with a persistent giant aneurysm is high risk. Warfarin is teratogenic in weeks 6 to 12. Use enoxaparin 1 mg/kg subcutaneously every 12 hours with a peak anti-Xa of 0.8 to 1.2 IU/mL 4 to 6 hours after the dose (1 mg/kg once daily at creatinine clearance under 30 mL/min), and stop the statin.

Monitoring. Kawasaki disease: echocardiography at diagnosis, at 1 to 2 weeks and at 4 to 6 weeks, then at 3, 6 and 12 months and yearly, and twice weekly while a giant aneurysm is expanding. Adults: CT angiography at 6 to 12 months, then every 1 to 2 years or when symptoms change, with stress imaging for new symptoms. INR every 4 to 12 weeks once stable (target 2.0 to 3.0), with bleeding review at each visit.

Referral and escalation. Refer to cardiology and a heart team, to paediatric cardiology for children, and to rheumatology for vasculitis. Urgent for acute coronary syndrome, suspected rupture, rapid enlargement or fever with an infected aneurysm.