Coronary Artery Ectasia with Thrombosis

Coronary artery ectasia is dilatation of a coronary artery segment to at least 1.5 times the diameter of the adjacent normal segment. Diffuse ectasia involves more than a third of the vessel length, and a focal dilatation of the same degree is an aneurysm. A giant aneurysm exceeds 20 mm, or 4 times the reference diameter. Thrombosis within an ectatic or aneurysmal segment causes acute coronary syndromes, usually through slow flow, stasis and distal embolisation.

Ectasia is found in about 1 to 5% of angiograms, more often in men and in the right coronary artery, then the left anterior descending and left circumflex. About half of cases are atherosclerotic, 20 to 30% are congenital, and the rest are inflammatory or connective tissue related.

Causes are atherosclerosis, Kawasaki disease (a leading cause in young patients), Takayasu arteritis, polyarteritis nodosa, systemic lupus erythematosus, Marfan and Ehlers-Danlos syndromes, syphilis, mycotic aneurysm, cocaine use, and iatrogenic injury (after drug eluting stents, atherectomy and balloon angioplasty).

Kawasaki disease classification by z-score: small 2.5 to under 5, medium 5 to under 10 with absolute diameter under 8 mm, and large or giant 10 or more or an absolute diameter of 8 mm or more.

Pathophysiology.

Degeneration of the media (loss of smooth muscle and elastin, matrix metalloproteinase activity) and vessel wall inflammation cause dilatation. Flow becomes slow and turbulent, with stasis and thrombus formation, vasospasm, and reduced coronary flow reserve.

Thrombus may occlude the vessel, embolise distally, or cause no reflow. Giant aneurysms also rupture, rarely.

Coexistent atherosclerotic stenosis adds to ischaemia. Ectasia is an independent marker of worse outcome after infarction.

Stable or unstable angina, myocardial infarction (ST elevation or non-ST elevation), arrhythmia, heart failure and, rarely, sudden death or rupture with tamponade. Some patients are asymptomatic with an incidental finding. A continuous murmur may be heard with a coronary fistula or large aneurysm. In young patients ask about Kawasaki disease, connective tissue disorders and cocaine.

• Coronary angiography: dilated segment with slow, swirling flow and delayed contrast washout, thrombus filling defect, and often coexisting stenosis. Intravascular ultrasound or optical coherence tomography clarify wall structure and thrombus, and measure diameter.
• CT coronary angiography or MRI for aneurysm size, wall thickness, thrombus, relation to branches and follow up without contrast arterial puncture.
• Echocardiography for left ventricular function and regional wall motion. ECG and troponin in acute events.
• Cause workup: ESR and C-reactive protein, antinuclear antibody, ANCA, syphilis serology, lipid profile, genetic testing and aortic imaging for connective tissue disorders, history of Kawasaki disease, and toxicology.

Differential diagnosis.

• Coronary artery fistula and spontaneous coronary artery dissection.
• Pseudoaneurysm after percutaneous intervention.
• Atherosclerotic remodelling with positive remodelling and plaque rupture.
• Coronary vasospasm and coronary embolism.

Acute myocardial infarction due to thrombosis in an ectatic artery.

• Primary percutaneous coronary intervention, accepting greater technical difficulty (large vessel, heavy thrombus burden, no reflow): aspiration thrombectomy selectively, large diameter balloon, intracoronary glycoprotein IIb/IIIa inhibitor (tirofiban 25 microgram/kg bolus over 3 minutes then 0.15 microgram/kg/min, halved at creatinine clearance under 30 mL/min), and distal protection in selected cases. Stents are not placed in the ectatic segment without secure landing zones, because of malapposition and stent thrombosis. Covered stents or bypass grafting are used for large aneurysms or perforation.
• Unfractionated heparin 70 to 100 units/kg bolus (60 units/kg with a glycoprotein IIb/IIIa inhibitor), with ACT 250 to 300 seconds, or bivalirudin 0.75 mg/kg bolus then 1.75 mg/kg/h during the procedure (reduce infusion to 1.0 mg/kg/h when creatinine clearance is under 30 mL/min).
• Aspirin 150 to 300 mg orally loading dose then 75 to 100 mg daily, with ticagrelor 180 mg loading dose and 90 mg twice daily (or clopidogrel 600 mg then 75 mg daily).

Long term antithrombotic therapy.

• Antiplatelet therapy for all patients with symptomatic ectasia: aspirin 75 to 100 mg daily.
• Oral anticoagulation is added for recurrent thrombosis, persistent thrombus, or a giant aneurysm: warfarin to INR 2.0 to 3.0, or apixaban 5 mg twice daily (2.5 mg twice daily if two of age 80 or over, weight 60 kg or under, creatinine 133 micromol/L or over). Evidence is limited, so decisions are by heart team judgement. Combined therapy raises bleeding risk: use omeprazole 20 mg daily and keep triple therapy short (up to 1 week, then a single antiplatelet drug with the anticoagulant).
• Kawasaki disease with giant aneurysm: aspirin 3 to 5 mg/kg daily (75 to 100 mg in adults) with warfarin to INR 2.0 to 3.0, or low molecular weight heparin, indefinitely while the aneurysm persists.

Risk factors and symptomatic therapy.

• Atorvastatin 40 to 80 mg once daily (LDL cholesterol under 1.4 mmol/L in established disease), blood pressure control, smoking cessation, glycaemic control.
• Beta blocker (metoprolol succinate 25 to 200 mg daily) for angina, tachycardia and after infarction when there is no contraindication.
• Nitrates may reduce flow in ectatic segments and are used with caution. Calcium channel blockers (amlodipine 5 to 10 mg daily) are used for spasm or angina.
• Treat the cause: corticosteroids and immunosuppression for active vasculitis, and treatment of syphilis.

Surgery. Aneurysm ligation or resection with bypass grafting for giant aneurysms (over 20 mm or 4 times the reference diameter), progressive enlargement, recurrent thrombotic events, compression of adjacent structures, rupture, infection, or associated severe stenosis needing grafting.

Monitoring. Clinical review and ECG at 1 and 3 months, echocardiography yearly, CT or MRI angiography at 6 to 12 months for aneurysms and with any change, INR monthly when stable, full blood count, creatinine and liver tests yearly, and review of bleeding risk at each visit.

Referral and escalation. Refer all patients with ectasia and an acute coronary syndrome for urgent catheterisation in a high volume centre. Refer giant aneurysms, recurrent thrombosis, rupture or tamponade to a heart team with surgical input.

Special groups.

• Pregnancy: avoid warfarin from 6 to 12 weeks (use low molecular weight heparin, enoxaparin 1 mg/kg subcutaneously every 12 hours with anti-Xa monitoring); avoid statins; direct oral anticoagulants are contraindicated.
• Children and adolescents (Kawasaki disease): follow up by paediatric cardiology; aspirin 3 to 5 mg/kg daily and weight based anticoagulation.
• Kidney impairment: adjust direct oral anticoagulants, enoxaparin and bivalirudin, and limit contrast.
• Region specific: infectious aneurysm (syphilis, mycotic) should be considered, and rheumatic disease or vasculitis may coexist.