Testing Acetylcholine Followed by Adenosine for Invasive Diagnosis of Coronary Vasomotor Disorders

The invasive diagnostic procedure, the so-called IDP, allows to identify functional coronary diseases, which are frequent mechanisms of angina in patients with unobstructed coronary arteries. The IDP provides a comprehensive evaluation of the dilatory and constrictive component of coronary vasomotion using intracoronary flow and pressure measurements. This is done at rest and during hyperemia, and also coronary spasm testing is performed.

There are different subtypes of functional coronary diseases, which are associated with different prognosis and treatment recommendations. The IDP helps to make the diagnosis and to find the optimal treatment. Begin by placing a guiding catheter suitable for the left coronary artery into the left main artery, and deliver another 5, 000 international units of heparin.

Advance the Doppler flow pressure wire through the guiding catheter into the left main artery, and after flushing to avoid any contrast in the catheter, calibrate the distal pressure sensor of the Doppler flow pressure wire. Place the tip of the wire in the proximal mid portion of the vessel, usually the left anterior descending artery, and perform thoracoscopy to record the wire position. Press record to record the signals on the system and assess and optimize the Doppler in ECG signal quality as necessary.

Once the recording has been started, inject six milliliters of the lowest acetylcholine concentration into the left coronary artery over a period of 20 seconds. Afterwards, flush the catheter with three to four milliliters of saline while performing continuous monitoring of the patient's symptoms, the 12-lead ECG, and the coronary blood flow velocity. Next, perform coronary angiography by injecting 10 milliliters of contrast agent through the catheter.

After one minute, inject six milliliters of the medium acetylcholine concentration before flushing with three to four milliliters of saline and recording the average peak velocity, the 12-lead ECG, and the patient's symptoms as demonstrated. Perform coronary and geography of the left coronary artery as previously demonstrated, and if no spasm occurs, continue with injecting 5.5 milliliters of the highest acetylcholine concentration, followed by three to four milliliters of saline. If no epicardial spasm occurs at the 100 microgram dose, continue with the 200 microgram dose while continuously monitoring the ECG and the patient symptoms.

When symptoms, ischemic ECG shifts, or epicardial spasm occurs, inject 200 micrograms of nitroglycerin and perform coronary angiography after one minute to document the reversion of the spasm. After the average peak velocity has returned to baseline and the patient's symptoms have returned to normal, press Base to capture the baseline values of the average peak velocity. Quickly inject a bolus of 3.5 milliliters of adenosine solution followed by a brief 10 milliliter saline flush.

Press the Peak Search button three heartbeats after the injection to initiate a peak search. The system will calculate and display the values for fractional flow reserve, coronary flow reserve, and hyperemic microvascular resistance. Repeat for at least two consistent measurements, then retract the wire and obtain a final angiogram to exclude any vessel injury.

According to the diagnostic criteria epicardial spasm can be diagnosed if transient ECG changes indicating ischemia, reproduction of the patient's usual anginal symptoms, and at least 90%vasoconstriction of an epicardial vessel as confirmed during coronary angiography can be observed. Spasm of the coronary microvasculature can be diagnosed if the patient's symptoms and ischemic ECG alterations occurred during provocation testing in the absence of epicardial vasospasm. Impaired microvascular vasodilation can be diagnosed by interpreting the CFR and HMR measurements following adenosine injections.

Depending on the cutoff values applied, a reduced CFR is defined as less than 2.0 or 2.5 or less. For HMR, data on the optimal cutoff values is scarce, but an increased microvascular resistance is currently defined as an HMR greater than 1.9 or greater than 2.4. In order to obtain an informative IDP, it is very important to ensure the quality of the Dopplar signal is appropriate and also to ensure that the 12-lead ECG during acetylcholine testing is interpretable.

This is required for an optimal IDP. The IDP can be expanded by additional tests such as the acetylcholine re-challenge after anti-vasospastic drug administration in order to evaluate its efficacy in the individual patient.