Coronary Slow Flow Phenomenon

Coronary slow flow phenomenon is delayed distal vessel opacification on angiography in one or more epicardial arteries that have no obstructive disease (stenosis under 40%). It is a disorder of the coronary microcirculation, and presents as recurrent angina, often with troponin rise and arrhythmia.

It is found in about 1 to 7% of patients undergoing angiography for chest pain. It is more common in younger men, smokers, and people with metabolic syndrome, obesity, and inflammatory states. It often recurs, with repeated admissions.

Diagnosis is by a corrected TIMI frame count of more than 27 frames in at least one vessel at 30 frames each second, or TIMI flow grade 2. Normal corrected counts are about 21 for the left anterior descending artery, 22 for the circumflex and 20 for the right coronary artery (the left anterior descending count is divided by 1.7 to correct for its length).

Pathophysiology.

Microvascular dysfunction with raised small vessel resistance, endothelial dysfunction with reduced nitric oxide, small vessel disease with wall thickening, inflammation, oxidative stress, and abnormal autonomic tone are proposed mechanisms.

Associations include smoking, metabolic syndrome, insulin resistance, obstructive sleep apnoea, vitamin D deficiency and raised inflammatory markers.

Reduced flow reserve causes ischaemia at rest and with exertion. Prognosis is usually good for survival, but quality of life is impaired and recurrent admission is common. Severe arrhythmia and sudden death are rare.

Rest or exertional chest pain, sometimes prolonged, with ST changes and troponin elevation in a minority, palpitations and syncope. Pain often occurs at rest and can resemble acute coronary syndrome. Examination is usually normal.

• Angiography: normal or nearly normal vessels with slow antegrade filling. Frame count method: first frame is when contrast fills 70% or more of the lumen and touches both borders, and the last frame is the arrival of contrast at the distal landmark (distal bifurcation of the left anterior descending artery, distal bifurcation of the branch with the longest total distance in the circumflex, and the first branch of the posterolateral artery in the right coronary artery).
• Exclude: epicardial spasm (provocation testing if indicated), coronary ectasia, myocarditis, Takotsubo syndrome, and microvascular angina from other causes.
• Physiological testing: Doppler wire or thermodilution: coronary flow reserve under 2.0 and index of microcirculatory resistance over 25 support microvascular disease.
• Troponin, ECG, echocardiography, ambulatory ECG, lipids, HbA1c, thyroid function, inflammatory markers, vitamin D, sleep study when symptoms suggest it, and cardiac MRI for myocarditis when troponin is raised.

Differential diagnosis.

• Microvascular angina with normal flow and coronary vasospastic angina.
• Myocardial infarction with non-obstructive coronary arteries.
• No reflow after intervention and coronary ectasia.
• Syndrome X and non-cardiac chest pain.

Evidence is limited, so treatment is symptom directed.

Risk factors. Stop smoking, lose weight, exercise, treat sleep apnoea, correct vitamin D deficiency, and control glucose and blood pressure.

Drugs.

• Aspirin 75 to 100 mg orally once daily, long term.
• Atorvastatin 20 to 40 mg orally once daily (maximum 80 mg), long term; lipids at 4 to 12 weeks and ALT at baseline. It improves endothelial function and frame counts.
• Calcium channel blocker: diltiazem sustained release 120 to 360 mg once daily (maximum 360 mg; monitor heart rate and PR interval; avoid with heart failure), or amlodipine 5 to 10 mg once daily (maximum 10 mg), or verapamil sustained release 240 to 480 mg once daily.
• Nicorandil 10 to 20 mg orally twice daily (maximum 30 mg twice daily); mouth ulcers; avoid with phosphodiesterase-5 inhibitors and hypotension.
• Dipyridamole 75 mg orally three times daily, as an add on for refractory symptoms; headache and hypotension.
• Trimetazidine 35 mg orally twice daily (modified release), where licensed; reduce to 35 mg once daily when creatinine clearance is 30 to 60 mL/min and avoid under 30 mL/min; avoid in parkinsonism and movement disorders.
• Ranolazine 375 mg orally twice daily, increased after 2 to 4 weeks to 500 to 750 mg twice daily (maximum 750 mg twice daily); avoid in cirrhosis and creatinine clearance under 30 mL/min; monitor QTc and renal function; interacts with strong CYP3A4 inhibitors and simvastatin (limit to 20 mg).
• Beta blockers are used for arrhythmia or palpitations (bisoprolol 2.5 to 10 mg daily), with caution when spasm is also suspected.
• Nitrates give variable relief and may reduce flow in some patients.

Acute episodes. Treat as an acute coronary syndrome until troponin and imaging exclude infarction. Glyceryl trinitrate 400 to 800 microgram sublingually for pain; intracoronary nitroglycerin 100 to 200 microgram or adenosine during angiography can speed flow, but are not a lasting treatment.

Monitoring. Symptoms, heart rate and blood pressure at 2 to 4 weeks, ambulatory ECG at 3 months for arrhythmia, lipids at 4 to 12 weeks, repeat angiography only for a change in pattern.

Referral and escalation. Refer for specialist assessment when symptoms are recurrent, troponin rises or arrhythmia occurs. Urgent referral for syncope, ventricular arrhythmia or ST elevation.

Special groups.

• Pregnancy: statins, nicorandil, ranolazine and trimetazidine are avoided; use calcium channel blockers (nifedipine, amlodipine) and beta blockers.
• Older adults: lower starting doses of calcium channel blockers.
• Kidney or liver impairment: give trimetazidine 35 mg once daily at creatinine clearance 30 to 60 mL/min and avoid it under 30; avoid ranolazine in cirrhosis and at creatinine clearance under 30 mL/min; reduce diltiazem and verapamil doses in hepatic impairment.