Chronic Total Coronary Occlusion

Chronic total coronary occlusion (CTO) is complete obstruction of a coronary artery, with antegrade flow grade 0, estimated to have lasted at least 3 months. The duration is judged from a history of infarction, a sudden change in angina, or prior angiography.

It is found in about 20% (range 15 to 30%) of patients with significant coronary disease who undergo angiography. The right coronary artery is the commonest site. Many patients are asymptomatic because collaterals supply the territory.

A CTO is associated with worse outcomes, particularly with multivessel disease, left anterior descending involvement and reduced ejection fraction.

Pathophysiology. Atherosclerotic occlusion matures into a fibrocalcific cap at each end with a plug between. Collaterals develop from the contralateral artery, septal branches or epicardial channels.

Ischaemia appears when demand exceeds collateral supply. Viable myocardium may be hibernating, and an occlusion of the donor artery causes infarction in two territories.

• Stable angina, often mild or atypical, exertional dyspnoea, reduced exercise capacity, or no symptoms.
• Heart failure from ischaemic cardiomyopathy.
• Ventricular tachycardia or defibrillator shocks from scar.
• Infarction in two territories when the donor artery occludes.
• Examination usually normal, or shows heart failure.

• Coronary angiography with bilateral (dual) injection to show retrograde collateral filling. Define the proximal cap, occlusion length, tortuosity and distal vessel.
• CT coronary angiography. Length, calcium, entry point and course of the occlusion, which helps plan the approach.
• J-CTO score (1 point each: blunt stump, calcification, bend over 45 degrees, occlusion length 20 mm or more, previous failed attempt). 0 easy, 1 intermediate, 2 difficult, 3 or more very difficult.
• Ischaemia and viability. Stress echocardiography, SPECT, PET or MRI. Late gadolinium enhancement involving under 50% of wall thickness suggests recovery of function after revascularisation. Echocardiography for ejection fraction.
• Renal function (contrast risk) and haemoglobin.

Differential diagnosis.

• Subtotal occlusion with functional occlusion (very slow flow, string sign)
• Acute or subacute occlusion
• Recanalised occlusion
• Severe stenosis with slow flow
• Spontaneous coronary artery dissection
• Coronary embolism or in situ thrombosis
• Anomalous coronary origin

Optimal medical therapy first, for all patients.

• Aspirin 75 to 100 mg orally once daily (usual maximum 325 mg daily). Atorvastatin 40 to 80 mg once daily (liver enzymes at baseline and 3 months, reduced dose with interacting drugs, avoided in pregnancy), aiming for LDL cholesterol under 1.4 mmol/L (55 mg/dL) with ezetimibe 10 mg once daily if needed.
• Bisoprolol 2.5 mg orally once daily, increased to 5 to 10 mg once daily, maximum 20 mg daily (do not exceed 10 mg daily at creatinine clearance under 20 mL/min or in severe liver impairment), aiming for a resting heart rate of 55 to 60/min. Or amlodipine 5 mg once daily, increased to 10 mg (maximum 10 mg daily; start 2.5 mg in older adults and liver impairment).
• Glyceryl trinitrate 400 microgram sublingually for attacks. Isosorbide mononitrate modified release 30 mg orally once daily in the morning, increased to 60 mg (maximum 120 mg daily), with a nitrate free interval. Contraindicated with phosphodiesterase type 5 inhibitors.
• Ranolazine 375 mg orally twice daily, increased after 2 to 4 weeks to 500 mg twice daily, maximum 750 mg twice daily (1,000 mg twice daily in some labels). Contraindicated in cirrhosis, at creatinine clearance under 30 mL/min, with QT prolongation, and with strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir). Limit simvastatin to 20 mg daily. Monitor QTc and renal function.
• Ramipril 2.5 mg orally once daily, increased every 2 to 4 weeks to 10 mg once daily (maximum 10 mg daily, 5 mg daily at creatinine clearance under 30 mL/min) for ejection fraction 40% or less, diabetes, hypertension or kidney disease, with potassium and creatinine 1 to 2 weeks after each change. Dapagliflozin 10 mg once daily for heart failure or diabetes (start at eGFR 25 mL/min/1.73 m2 or more, contraindicated in type 1 diabetes).

CTO PCI. Indicated for persistent disabling angina despite optimal medical therapy, with suitable anatomy, ischaemia or viable myocardium, and an experienced operator. It improves angina and quality of life. Survival benefit is unproven, and it is not done for asymptomatic patients.

• Techniques: antegrade wire escalation, antegrade dissection and re-entry, and retrograde crossing through collaterals. Success is 85 to 95% in experienced centres and lower in general practice.
• Risks: coronary perforation (about 3 to 5%) with tamponade in about 0.5 to 1%, contrast nephropathy, radiation skin injury, periprocedural infarction (about 2 to 3%), and death (about 0.2 to 0.5%).
• Antithrombotic therapy: aspirin 75 to 100 mg daily and clopidogrel 600 mg once then 75 mg daily (avoid omeprazole and esomeprazole, use pantoprazole 40 mg daily). Unfractionated heparin 70 to 100 units/kg intravenously, activated clotting time over 300 seconds (over 350 seconds with a retrograde approach), checked every 20 to 30 minutes. After a drug eluting stent give dual antiplatelet therapy for 6 months (12 months after complex PCI, shorter with high bleeding risk), then a single antiplatelet drug.
• Perforation: balloon inflation to seal the vessel, protamine sulphate 1 mg for each 100 units of heparin given in the previous 2 hours (slowly, not over 50 mg in 10 minutes), pericardiocentesis for tamponade, and a covered stent or coil embolisation for distal perforation.
• Kidney protection: keep contrast volume (mL) under 3.7 times the creatinine clearance (mL/min). Give 0.9% saline 1 mL/kg/h for 6 to 12 hours before and 12 hours after (0.5 mL/kg/h with ejection fraction 35% or less), withhold nephrotoxic drugs, and check creatinine at 48 to 72 hours.
• Radiation: record air kerma dose, and review the skin at 2 to 4 weeks after a cumulative dose over 5 Gy.

Bypass surgery is preferred with multivessel disease, diabetes, left main disease or reduced ejection fraction when anatomy is unsuitable for PCI.

Special groups. Diabetes and chronic kidney disease: take extra care with contrast and prefer surgery for multivessel disease. Older adults: choose by symptoms and frailty.

Monitoring. Symptoms and ECG at 1 month, then every 3 to 6 months. Echocardiography at 6 to 12 months after PCI. Stress imaging or CT when symptoms recur, since reocclusion occurs in a minority. Creatinine at 48 to 72 hours.

Referral and escalation. Refer to a centre with CTO expertise and a heart team for refractory angina. Urgent for acute coronary syndrome in the donor artery, heart failure or ventricular arrhythmia.