Acetylcholine Re-Challenge After Intracoronary Nitroglycerine Administration

The invasive coronary function test is crucial for the diagnosis and treatment of coronary vasomotor disorders. It helps in assessing endothelial coronary dysfunction, epicardial vasospasm, and microvascular angina. The latter comprises of a vasoconstriction of abnormal dilatation of the microcirculation.

This technique enables safe assessment of intracoronary administration of acetylcholine that may distinguish different endotypes of coronary vasospasm. And finally, with the use of the re-challenge method, we can identify patients with both microvascular angina and epicardial vasospasm. Begin by mixing 20 milligrams of acetylcholine with two milliliters of the solvent provided with the package.

Add one milliliter of the acetylcholine solution to 499 milliliters of 0.9%sodium chloride to create the stock solution corresponding to a dosage of 20 micrograms per milliliter. Fill a sterile dish with 50 milliliters of the stock solution. Under sterile conditions, prepare five 10 milliliter syringes using the stock solution for the intracoronary injection as described in the text manuscript.

For the left coronary artery, position the tip of the diagnostic catheter in the left main coronary artery. Confirm the position of the catheter by injecting two milliliters of the contrast agent. Inject five to ten milliliters of the contrast agent to visualize the coronary arteries in different projection views.

Connect the Doppler guide wire to the system, and zero the pressure on the console and the aortic pressure on the hemodynamic system. Advance the Doppler guide wire through the guiding catheter into the ostium of the coronary artery with the Doppler guide wire's pressure sensor placed just distally to the tip of the guiding catheter. After normalization, reintroduce the wire via the microcatheter into the proximal or mid LAD, and acquire a stable flow signal.

Document the position of the wire using fluoroscopy, and exclude any relevant epicardial stenosis. Administer the first syringe containing two micrograms of acetylcholine into the left coronary artery through the guiding wire. Inject this in 60 seconds while continuously monitoring the ECG, APV, and the patient's symptoms.

After flushing the remaining acetylcholine in the guiding wire, inject 10 milliliters of contrast reagent into the catheter. Bookmark and print a 12-lead ECG after every dose of acetylcholine, or when the patient's symptoms or ECG changes occur. If diagnostic criteria are not met, administer the second syringe containing 20 micrograms of acetylcholine as demonstrated.

Pause for three minutes between every dose. Inject 10 milliliters of contrasting reagent as demonstrated. If diagnostic criteria are not met after the second dose, administer the third syringe containing 100 micrograms of acetylcholine.

Monitor the patient's symptoms along with ECG and APV. Then inject 10 milliliters of contrasting reagent. Inject 200 micrograms of intracoronary NTG into LAD after the test, or when severe symptoms, ischemic ECG changes, or epicardial spasms occur.

Inject 10 milliliters of the syringe containing the acetylcholine dose that previously induced vasospasm into the guiding in 60 seconds while continuously monitoring the ECG, APV, and the patient's symptoms. Image the target vessel in the same projection as done in the baseline angiography after the 10 milliliters acetylcholine dose. Inject 200 micrograms of intracoronary NTG into each target vessel after the test or when severe symptoms, ischemic ECG shifts, or epicardial spasm occurs.

Perform coronary angiography of the target vessel after one minute, or when the APV has returned to baseline and no symptoms are present to document reversion of spasm. The distinction between epicardial and microvascular spasms was made by comparing coronary diameter reduction in reaction to the spasm provocating dose and NTG. The coronary angiography performed during rest showed no significant lumen reduction in the LAD.

At the fourth dose of acetylcholine, epicardial lumen reduction occurred together with ECG changes and recognizable symptoms, and therefore met the diagnostic criteria for epicardial vasospasm. When the coronary artery was re-challenged after intracoronary administration of NTG, some vasoconstriction occurred, although no more than 90%lumen reduction was observed, and the severity of anginal complaints was reduced. At the fourth dose, epicardial vasoconstriction causes very high APV values, whereas the preventive effect of NTG causes lower APV values because the epicardial coronary artery does not constrict.

Obtaining a visual analog scale score while performing an acetylcholine re-challenge can prove helpful in quantifying the improvement in symptoms. Improvement in APV and provoked ischemic ECG changes, and the severity of vasoconstriction on angiography can help as an objective measure on the preventive effect of NTG. Continuous assessment of Doppler flow provided valuable information during spasm provocation.

It provided a safety feature as flow alterations often occurred before ECG changes. With the use of this technique, we can identify patients with angina pectoris due to vasomotor disorders, and reveal the underlying mechanisms such as coronary endothelial dysfunction, coronary artery spasm, and microvascular angina.