The invasive functional assessment of the epicardial coronary circulation and microcirculation is extremely important for understanding the functional and hemodynamic impact of stenoses in the coronary arteries and the blood flow within them. Performing these specific tests significantly contributes to the accurate, timely, and precise diagnosis and treatment of coronary artery disease.
In particular, studies such as fractional flow reserve under conditions of maximum hyperemia (Fractional Flow Reserve – FFR), resting indices (Resting Full Cycle Ratio – RFR and Instantaneous wave-Free Ratio – iFR), coronary flow reserve (Coronary Flow Reserve – CFR), and the index of microcirculatory resistance (Index of Microcirculatory Resistance – IMR) are the most frequently used functional techniques for assessing the coronary arteries and the coronary microvascular network.
What is fractional flow reserve (Fractional Flow Reserve – FFR)?
Fractional flow reserve (FFR) is an invasive functional method that evaluates the impact of underlying stenoses in the coronary arteries on total blood flow within them. FFR indicates how much the blood flow in a specific coronary artery is reduced due to a stenosis, compared to the normal flow if the stenosis were not present. Specifically, an FFR value of 0.75 means that the stenosis reduces blood flow by 25% compared to the normal flow if the stenosis were absent.
The test is based on the insertion of a specialized guide wire with a pressure and temperature sensor into the coronary artery, followed by intravenous administration of a specific drug, adenosine, which induces conditions of hyperemia and stress on the heart.
The infusion of the drug lasts approximately 2 minutes, and during this time, patients may experience a sensation of warmth and burning in the chest, shortness of breath, and headache. These symptoms subside immediately after discontinuation of the drug within a few seconds. A pathological FFR value is defined as ≤ 0.80.
In recent years, this test can also be performed without adenosine administration, making the procedure faster and more tolerable for the patient. These are the resting tests such as iFR (Instantaneous Free Wave Ratio) and RFR (Resting Full Cycle Ratio), with a pathological value defined as ≤ 0.89.
What are the Resting Full Cycle Ratio – RFR and Instantaneous Free Wave Ratio – iFR tests?
These tests are alternative methods for the functional evaluation of blood flow in the coronary arteries, which do not require adenosine administration. Both RFR and iFR are measured during resting conditions, without the need to induce hyperemia through systemic administration of adenosine.
As a result, patients avoid the systemic effects of adenosine and thus the associated unpleasant symptoms such as flushing, headache, burning sensation, shortness of breath, and chest discomfort. A pathological RFR or iFR value is ≤ 0.89.
The procedure is usually faster and generally much better tolerated by patients, as it does not cause the side effects associated with adenosine. However, it should be noted that in 20% of cases, there is a discrepancy between the results of FFR and RFR/iFR studies, i.e., a negative result for ischemia with iFR/RFR and a positive result with FFR or vice versa.
What is coronary flow reserve (Coronary Flow Reserve – CFR)?
Coronary flow reserve (CFR) assesses the functional ability of the entire coronary network to increase blood flow (perfusion) to the heart during increased cardiac workload under stress conditions. The procedure involves intracoronary administration of room-temperature saline at rest and during systemic intravenous administration of adenosine to induce maximum hyperemia.
CFR is calculated by comparing total blood flow before and during systemic adenosine administration. Normally, the coronary network can increase blood flow by more than 2.5 times. CFR values ≤ 2.5 are considered pathological and suggest possible coronary microvascular dysfunction.
What is the Index of Microcirculatory Resistance – IMR?
The measurement of microvascular resistance (Index of Microcirculatory Resistance – IMR) is a test often combined with CFR to functionally assess coronary microcirculation.
While CFR reflects the function of both the epicardial and microvascular coronary networks, IMR specifically quantifies resistance in the microvascular network of the heart and is a more specific indicator of microvascular function.
The procedure involves intracoronary administration of room-temperature saline during systemic intravenous administration of adenosine and the induction of maximum hyperemia. With the Coroventis system, both CFR and IMR can be measured simultaneously.
What is coronary endothelial function testing – provocation test following intracoronary acetylcholine administration?
This is the test of choice for diagnosing vasospastic angina – that is, severe paradoxical spasm of the coronary arteries. During the test, acetylcholine is administered into the coronary arteries, a substance that normally causes vasodilation of the heart’s vessels.
However, in patients with vasospastic angina, acetylcholine causes severe arterial spasm accompanied by chest pain and pathological ischemic changes on the electrocardiogram. Timely diagnosis of vasospastic angina leads to targeted anti-anginal therapy with immediate improvement in symptoms and quality of life in these patients.
The total duration of all tests, including diagnostic coronary angiography, does not exceed 1 hour. After the completion of the tests, the patient can mobilize immediately.
It is recommended to discontinue anti-anginal medications 24–48 hours before the tests and to avoid consuming caffeine-containing drinks for 24 hours.
Where are the functional assessment tests of the epicardial and microvascular coronary circulation performed?
The FFR, RFR/iFR, CFR, IMR tests and the provocation test with intracoronary acetylcholine administration are performed in the catheterization laboratory, usually after diagnostic coronary angiography, in specialized cardiology centers and hospitals equipped with the necessary technology and expertise for these invasive diagnostic procedures. These centers are staffed with trained personnel and possess the required experience and knowledge for the execution and interpretation of these tests.
Are there any complications associated with these tests?
The FFR, RFR/iFR, CFR, IMR tests and the acetylcholine provocation test are generally considered safe, although some side effects may occur. During adenosine administration, patients may experience chest burning, flushing, shortness of breath, or headache, while intracoronary acetylcholine administration may cause transient heart rhythm disturbances, conduction abnormalities such as bradycardia, and coronary artery spasm with chest pain.
Most side effects are self-limiting and usually resolve immediately after discontinuation of the medication (adenosine or acetylcholine). In cases of acetylcholine-induced spasm, intracoronary nitrates are administered to relieve the spasm and alleviate the associated chest pain.
What is the cost of these tests?
The final cost of these tests may vary and can be influenced by the equipment used, the services provided, and other factors.
In summary, FFR, RFR/iFR, CFR, IMR, and the acetylcholine provocation test are valuable tools for the accurate evaluation of epicardial and microvascular coronary circulation and endothelial function, providing critical information necessary for proper diagnosis and treatment of coronary artery disease and angina-related symptoms.
