Clinical use of coronary artery pressure flow measurements

INTRODUCTION — 

Coronary artery pressure flow measurements are catheter-based intracoronary tests that can help determine the hemodynamic significance of coronary artery stenoses. In some patients, the coronary angiogram identifies lesions that are not clearly flow-limiting (eg, in the range of 30 to 70 percent luminal diameter reduction) (figure 1). In such cases, coronary artery pressure or flow measurements can facilitate clinical decision making regarding the need for revascularization, particularly in individuals without noninvasive stress test documentation of myocardial ischemia.

The other purpose of coronary artery pressure flow measurements is to diagnose coronary microvascular dysfunction often associated with chest pain syndromes (ischemia) in the absence of coronary artery obstructions (ischemia with no obstructive coronary arteries [INOCA]). The approach to diagnosis of INOCA is discussed separately. (See "Myocardial infarction or ischemia with no obstructive coronary atherosclerosis".)

LIMITATIONS OF CONTRAST ANGIOGRAPHY — 

The coronary angiogram may not accurately identify whether a specific lesion causes myocardial ischemia. This is particularly true among lesions with intermediate angiographic stenosis (30 to 70 percent diameter narrowing). Angiography produces a two-dimensional silhouette image of the three-dimensional lumen ("lumenogram") (figure 1), and its interpretation is subject to imaging artifacts that include contrast streaming, branch overlap, vessel foreshortening, calcification, and ostial origins. These factors lead to a weak association between angiographic stenosis and ischemia identified from stress testing [1].

PHYSIOLOGY OF STENOTIC FLOW — 

The hemodynamic significance of a stenosis depends both on the specific lesion configuration and the amount of flow to the subtended myocardium:

●Morphologic factors – Pressure proximal to a flow-limiting lesion (most often represented by aortic pressure) is higher than it is distal to a flow-limiting lesion. Epicardial artery resistance to flow (most often due to significant atherosclerotic obstruction) causes energy loss, which translates into loss of pressure downstream from the stenosis. The amount of pressure loss depends on multiple factors that include the specific morphology of the stenosis (different entrance or exit angles, lesion lengths, lumen shape, irregularity), extent of atherosclerotic disease, stenosis location within the vessel (ie, proximal or distal), size of the normal reference segment near the stenosis, and rate of coronary blood flow. The differential pressure ("delta-P") is a function of forces of viscosity and flow separation. Broadly, these factors affect resistance and flow ("Q").

●Mass of myocardium – Coronary blood flow is also a function of the myocardial mass supplied by the vessel [2].

FRACTIONAL FLOW RESERVE

Hyperemic pressure ratio, FFR — Fractional flow reserve (FFR) is a measure of the ischemic potential of a suspicious coronary artery lesion obtained by comparing pressure beyond a suspicious coronary stenosis to pressure proximal to that coronary stenosis during hyperemia (ie, adenosine injection or infusion).

●General procedure for measurement – To measure FFR, a pressure-sensing wire is advanced over the lesion in question, hyperemia is established with infusion of a vasoactive agent, pressure is continuously measured distal and proximal to the lesion, and the ratio of the distal and proximal pressures are calculated. In scenarios where diffuse disease is suspected, measurement is performed during a pullback of the wire across the diseased segment. Specific details are discussed elsewhere in this topic. (See 'Translesional pressure measurement' below.)

●Interpretation of values – The normal value for FFR is 1 for each patient, coronary artery, myocardial distribution, and microcirculatory status. An FFR value of ≤0.75 in patients with stable angina is strongly related to provocable myocardial ischemia using multiple stress testing methods. Because of variance among FFR measures and lack of agreement between stress test results, FFR values between 0.76 and 0.8 are considered a "gray zone."

During pullback, diffuse flow-limiting disease is defined as an abnormal FFR value measured over the diseased segment (ie, ≤0.75) in which there is no discrete pressure change along the length of the suspected lesion. The degree to which flow-limiting disease is diffuse versus focal can be quantified.  

●Clinical correlation – Clinically, FFR is a measure of the ischemic potential of a coronary artery stenosis. FFR was initially validated against a three-stress-test standard of inducible ischemia, which provided a threshold value of 0.75 to define ischemia-associated lesions [3]. The sensitivity of FFR is 88 percent, and the specificity is 100 percent.

FFR values reflect a continuum of risk such that lesions with more severely abnormal FFR (ie, <0.6) have a higher risk of clinical events and thus are more likely to benefit from revascularization [4].

●Rationale – The ratio of pressure measured distal to the lesion and pressure measured in the aorta (Pd/Pa) during hyperemia is called FFR. FFR represents the fraction of normal flow through a diseased artery relative to estimated flow through the same theoretically normal artery.

FFR is derived from the ratio of stenotic flow (Qs) to theoretically normal artery flow (Qn) during hyperemia, as follows:

Where Pd is coronary pressure distal to the stenosis, Pa is aortic pressure, R is myocardial bed resistance, and Pv is venous or right atrial pressure. Since R is constant and Pv is negligible relative to Pa, the formula simplifies to:

Because FFR measures are obtained during hyperemia, autoregulation is abolished and microvascular resistance fixed and minimal. In stable patients, FFR is largely independent of basal flow, driving pressure, heart rate, systemic blood pressure, or status of the microcirculation. Under these conditions, coronary blood flow is directly related to coronary pressure. FFR reflects both antegrade and collateral perfusion. In acute myocardial infarction (MI), FFR is a less reliable measure of coronary stenosis. (See 'Acute coronary syndrome' below.)

Nonhyperemic pressure ratios (eg, iFR) — The instantaneous wave-free ratio (iFR) and other nonhyperemic pressure ratios (NHPR) such as the diastolic pressure ratio (dPR) and diastolic hyperemia-free ratio (DFR) are other measures of the ischemic potential of suspicious coronary artery lesions. In contrast with FFR, these measures do not require hyperemia. NHPRs can be divided into diastolic subcycle (eg, iFR, dPR, DFR) or whole-cycle indices (eg, Pd/Pa, resting full-cycle ratio [RFR]).

●General procedure for measurement – iFR and other NHPRs are measured by positioning a pressure wire across a suspected stenosis. Pressures distal to the lesion and proximal to the lesion (ie, in the aorta) are measured during diastole (ie, the wave-free interval) using specialized software.

●Interpretation – The best cutoff iFR value is ≤0.89 for strong agreement with FFR of ≤0.8 [5,6]. All NHPR thresholds are numerically and clinically equivalent to iFR with a threshold of 0.89 (except Pd/Pa at 0.91) and can be substituted for iFR in clinical practice.

●Clinical correlation – Clinical validation studies compared iFR with FFR and found an 80 to 85 percent concordance. Despite different ways by which various NHPR values can be calculated, evidence suggests that diastolic NHPRs are numerically identical with each other and with respect to their agreement with FFR [7].

In comparative studies, FFR, iFR, and whole-cycle Pd/Pa have approximately 80 percent agreement with noninvasive measures of ischemia such as positron emission tomography coronary flow reserve [7-13].

●Rationale – During the wave-free period, microvascular resistance is low and constant, and, therefore, the translesional pressure ratio can be used in a manner similar to FFR without the need for adenosine [8]. The main advantage of the NHPRs relative to FFR is that there is no need to establish hyperemia, which is associated with additional cost, time, and side effects.

Less common measures — Less commonly used FFR-like measures include:

●Contrast media FFR – Contrast media FFR (cFFR) is defined as the lowest mean Pd/Pa value after intracoronary administration of radiographic contrast medium (8 to 10 mL). Contrast media induces 50 to 60 percent of adenosine maximal hyperemia. The CONTRAST study reported a best cutoff value of 0.83 for cFFR for prediction of FFR [14]. Additionally, cFFR was more accurate than resting Pd/Pa (using a cutoff of 0.92) and iFR (cutoff of 0.90) in predicting FFR [14]. A hybrid approach has been proposed, deferring revascularization when cFFR is >0.88 and proceeding to stenting when ≤0.83. cFFR is applicable to any pressure sensor wire and monitoring system, using existing FFR software. cFFR is free of side effects other than those related to contrast media.

Since the contrast-induced hyperemia is relatively short-acting and not steady, cFFR is not suitable for pressure pullback analysis. Often, a stepwise approach for lesion assessment begins with an NHPR measure. If the NHPR measure is unclear, it is reasonable to obtain cFFR and, if necessary, FFR.

●Angiographically derived FFR – There are several methods to obtain FFR from angiography, one of which uses three-dimensional reconstruction of the target artery from angiographic images to infer FFR values with computational fluid dynamics or fast flow modeling [15]. The result is a so-called angiographically derived FFR, a measure that is interpreted using the same thresholds as invasive guidewire-based FFR [16-18]. Angiographic FFR has sensitivity, specificity, and diagnostic accuracy similar to wire-based FFR (88, 95, and 93 percent, respectively) [18].

Another method, the quantitative flow reserve (QFR), was validated in the FAVOR II study and had a vessel-level diagnostic accuracy of 98 percent and patient-level diagnostic accuracy of 92 percent [17]. In addition, the FAVOR II trial demonstrated that QFR had higher sensitivity and specificity in comparison with two-dimensional quantitative coronary angiography using FFR as the standard (88 versus 46 percent and 88 versus 77 percent, p<0.001 for both) [17]. The overall diagnostic accuracy of QFR was 88 percent. However, clinical outcomes appear to be worse with QFR. In the FAVOR III Europe trial, in which 2000 patients were randomly assigned to either a QFR-guided or wire-based FFR-guided revascularization strategy, the composite endpoint of death, myocardial infarction, and unplanned revascularization at 12 months occurred more frequently in the QFR-guided group (6.7 versus 4.2 percent) [19].

Advantages of in-laboratory angiographically derived FFR include reduced time and cost for obtaining an FFR measure; angiographically derived FFR obviates the need for pressure guidewire use and pharmacologic hyperemia. Limitations include needing to improve the routine image acquisition to provide consistent visualization of the entire coronary tree, optimal vessel opacification, and no panning.

●IVUS- and OCT-derived FFR – Images of the coronary artery lumen obtained with intravascular ultrasound (IVUS) or optimal coherence tomography (OCT) can be used to create three-dimensional artery/lumen reconstructions and derive FFR values such as the ultrasonic flow ratio (UFR) and OCT-derived FFR (OFR).

When UFR was compared with wire-based FFR, there was high agreement between UFR and good correlation with FFR with acceptable computational time and reproducibility [20]. Similarly, the diagnostic accuracy of OFR is favorable compared with wire-based FFR [21].

●Computed tomography-based FFR – Outside the catheterization lab, the estimation of FFR from coronary computed tomographic angiography (CTA-FFR) may be used as a screening tool for anatomic disease. CTA-FFR has strong correlation (approximately 80 percent agreement) with pressure wire-measured FFR. In a meta-analysis of 13 studies assessing the diagnostic performance of angiographically derived FFR using different computational models, CTA-FFR had a pooled sensitivity of 89 percent and specificity of 90 percent with a positive likelihood ratio of 9.3 (95% CI 7.3-11.7) and negative likelihood ratio of 0.13 (95% CI 0.07-0.2) [22,23].

CORONARY FLOW RESERVE (CFR)

CFR — Coronary flow reserve (CFR) is the ratio of maximal hyperemic to resting coronary flow or flow velocity and describes the ability of the coronary vascular bed to increase flow in response to increased myocardial oxygen demand from pharmacologic (eg, adenosine) stimuli.

●General procedure for measurement – To measure CFR, a wire that measures flow via thermodilution or via Doppler velocity is placed in the target artery. Then, the ratio of maximal hyperemia to basal flow is calculated by comparing flow distal with a lesion with hyperemia or exercise with flow distal to a lesion at rest.

●Interpretation of results and clinical correlation – In young adults, normal CFR values range from 3.5 to 5. In adult patients undergoing cardiac catheterization for suspected coronary artery disease (CAD), the average value is 2.7. A CFR <2 is a commonly associated with abnormal ischemic testing. However, since CFR measures the summed response of both the epicardial and microvascular circulations, it is not specific for epicardial stenoses and is of limited value for clinical decision making in patients with stenotic vessels.

The main role of CFR is in the evaluation of microvascular disease, which is discussed separately. (See "Microvascular angina: Angina pectoris with normal coronary arteries", section on 'Coronary flow reserve on angiography'.)

●Rationale – Normal epicardial vessels have negligible resistance to flow. In abnormal vessels and if normal autoregulation is intact (eg, microvascular vasodilation), resting coronary blood flow can remain constant up to a vessel diameter stenosis that exceeds 85 to 90 percent.

Under hyperemic conditions, autoregulation is exhausted, and maximal coronary blood flow begins to decline from maximal when vessel diameter stenosis exceeds 60 percent [24]. When a stenosis becomes "critical" (eg, a stenosis >90 percent diameter), the flow reserve is exhausted (ie, autoregulation cannot regulate blood flow and maintain resting myocardial flow, which may decrease).

CFR measures the summed response of flow moving through the epicardial or "conductance" vessels (called R1 resistance, large superficial arteries, >400 microns diameter) and into the "resistive" (arteriolar and capillary resistance vessels, <400 microns) smaller arteries.

Because CFR is the ratio of hyperemic/basal flow, its value can change by any factor that affects basal or hyperemic flow, both of which are influenced by hemodynamics, loading conditions, and contractility.

Index of microvascular reserve (IMR) — The index of microvascular resistance (IMR) normalizes CFR for pressure loss beyond a stenosis and better reflects the status of the microvasculature in patients with obstructive CAD [25]. IMR is calculated by the ratio of Pd/coronary flow at hyperemia using thermodilution flow arrival time (Tmn) and translesional pressure gradient (delta-P), as follows:

Delta-P is the Pd-Pa; during maximal hyperemia, Pv is negligible, resulting in IMR = Pd x Tmn.

The normal value of IMR is <25. Unlike CFR, IMR corrects for translesional hemodynamics, making it more reproducible. IMR is also more specific for the microvasculature, whereas CFR is affected by epicardial stenosis. IMR <40 immediately after primary percutaneous coronary intervention for ST-elevation MI (STEMI) predicts the amount of myocardial damage and outcomes [26].

TECHNICAL CONSIDERATIONS

Hyperemia — Adenosine, a potent short-acting hyperemic stimulus, is the agent most widely used to establish hyperemia. Adenosine has a low risk of serious complications. The usual doses of adenosine used to establish hyperemia for fractional flow reserve (FFR) or coronary flow reserve (CFR) measurement are:

●Intracoronary (IC) bolus injection: 50 to 100 mcg in the right coronary artery or 100 to 200 mcg in the left coronary artery (eg, left anterior descending or circumflex artery).

●Intravenous (IV) infusion: 140 mcg/kg/min.

IV and IC adenosine produce equivalent hyperemia [6]. Compared with IC, IV administration has a higher incidence of side effects such as flushing, chest tightness, bronchospasm, nausea, and transient atrioventricular block or bradycardia (<2 percent of patients). IV infusion is generally preferred over bolus injection for ostial lesion assessment or for use during pressure pullback measurement.

Translesional pressure measurement — The steps to measure translesional pressures are as follows:

●The pressure wire and guide catheter pressure transducers are set to zero (ie, open to atmosphere) on the table.

●After anticoagulation (IV heparin, usually 70 units/kg) and IC nitroglycerin (100 to 200 mcg bolus) are administered, the guidewire is advanced to the coronary ostium. The pressure wire signal and the guide pressure are electronically matched (ie, equalized, also called normalized) before crossing the stenosis.

●The guidewire is then advanced across the stenosis approximately 10 artery diameters (approximately 20 mm) distal to the coronary lesion in question.

●After flushing the guide catheter, wait one to two minutes to ensure basal flow is stable (contrast media or saline injections produce submaximal hyperemia). Once basal flow is stable, nonhyperemic pressure ratio (NHPR) is measured in duplicate.

●Submaximal hyperemic Pd/Pa measured during contrast media hyperemia (cFFR) can follow NHPR, and, if borderline, FFR with adenosine (IC or IV) may be performed.

●cFFR or FFR is measured at the lowest Pd/Pa ratio after the onset of hyperemia, usually within two minutes for IV adenosine and at 15 to 20 seconds after IC adenosine or contrast media.

●After percutaneous coronary intervention, NHPR/FFR pressure pullback can assess any residual disease or hidden lesions in the target vessel or other territories.

●At the end of the FFR/NHPR measurements, the pressure wire should be pulled back to the coronary ostium to check for pressure signal changes. If the signal drift (unequal pressures) is large (>3 mmHg), the last measurements will need to be repeated after re-equalization of guide and wire pressures in the aorta.

FFR and NHPR can be used to characterize complex lesions with pullback pressure recording or imaging methods [27].

CFR measurement — CFR can be measured with intracoronary wires that measure either velocity or flow (ie, thermodilution). Using a Doppler flow wire with an ultrasound transducer at the tip, CFR is obtained after recording the basal and peak hyperemic average peak velocity after adenosine (either bolus or IV infusion).

For the thermodilution CFR technique, a specialized pressure guidewire is used, which has a proximal and distal thermistor (shaft and tip of guidewire) that measures temperature arrival times after injection of a 3 mL bolus of saline. To calculate CFR, temperature curves are recorded at rest during bolus injections of 3 mL of saline and again during hyperemia induced by adenosine [28].

The index of microcirculatory resistance (IMR) is the ratio of distal pressure, (Pd)/mean transit time (Tmn) measured simultaneously during hyperemia:

If using IV adenosine, operators should be aware of pressure fluctuations during the infusion period. FFR signal displays automatically provide the FFR at the lowest Pd/Pa, deemed to be most the accurate value.

Pitfalls — Accurate measurement of intracoronary flow requires identifying and resolving common pitfalls. Issues that can significantly impact pressure measurements include:

●Changes in basal flow – Basal coronary flow significantly impacts NHPR reproducibility. The coronary circulation is adapted to maintain stable resting flow to maintain homeostasis principally through autoregulation. Transient hemodynamic changes can alter basal flow and subsequent NHPR readings. Increased adrenergic responses, anemia, or hyperthyroidism, for example, can change hemodynamic status (ie, heart rate, blood pressure, contractility) with a reset of basal flow.

In addition, guide catheters with side holes should not be used during intracoronary flow and pressure measurement because they create an artificial stenosis through the holes. Removing the guide catheter from the coronary ostium after giving the hyperemic agent will avoid this pitfall.

The most common pitfalls of FFR or NHPR are guide pressure damping, failure to capture the minimum Pd/Pa, and signal drift [29]. For all lesion assessments, operators should minimize vasomotion with IC nitroglycerin (100 to 200 mcg) several minutes before measurements.

●Unexpected hyperemia – Transient hyperemia may occur after intracoronary saline or radiographic contrast media injection. Thus, resting measurements should be acquired after at least 30 seconds after injection of contrast, nitroglycerine, or saline.

●Heart rate – Increasing the heart rate likely affects all intracoronary flow indices (usually by lowering the readings) which may result in the misclassifications of lesions. Since diastolic subcycle NHPRs are derived from a segment of the diastolic period, tachycardia (which shortens diastole) may be more problematic for whole cycle NHPR indices (Pd/Pa, resting full-cycle ratio [RFR]). Heart rates >130 beats per minute are likely to lead to inaccurate recordings, and some algorithms will not perform a reliable computation in this setting.

●False negative results – False negative FFR (ie, a high FFR) values may occur with guide catheter pressure damping (preventing flow into the vessel), failure to induce hyperemia (wrong concentration, poor intravenous infusion), or acute coronary syndromes with an impaired myocardial bed.

●False positive results – False positive FFR values are very uncommon and most often the result of technical failures due to inaccurate calibration, tubing leaks, guidewire signal drift downward, or aortic pressure drift upward. Signal drift is identified by the failure to rematch aortic and wire pressures after measurements are made. Drift affects NHPRs more than FFR values. A false positive FFR may occur in the very distal portions of the vessel where the cumulative effect of diffuse disease is most prominent.

COMPLICATIONS — 

Complications of sensor-tipped guide wires in the coronary arteries are rare and no greater than those associated with diagnostic angiography and coronary angioplasty wire-related events. In a large study of the intracoronary guidewire for coronary flow reserve, the complication rate was 3 percent (27 complications among 906 patients). Adverse cardiac events included severe transient bradycardia (1.7 percent), vasospasm in 1 percent, ventricular fibrillation in 0.1 percent, and hypotension with bradycardia and ventricular extrasystole in 0.1 percent. The incidence of a complication was significantly higher in transplant recipients than in patients who underwent either diagnostic or interventional procedures (12.99 versus 2.43 versus 0.94 percent, p<0.001). All complications were medically treated successfully. Intracoronary pressure/flow wires are safe with low rates of complications most often related to adenosine administration [30].

CONTRAINDICATIONS — 

Contraindications to invasive translesional pressure or flow measurement include sensitivity to adenosine (including baseline long QT syndromes) or inability to use heparin anticoagulation. Relative contraindications include target lesion assessment in a patient with active acute coronary syndromes (injured myocardium prevents maximal hyperemia) or critical left main stenosis.

CLINICAL SCENARIOS

Stable ischemic heart disease — In patients with angina despite maximal medical therapy who have not undergone a test for inducible ischemia but who proceed to invasive coronary angiography and are found to have coronary artery stenoses of intermediate severity (eg, 30 to 70 percent), it is reasonable to measure fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) at the time of coronary angiography to identify the ischemic potential of such lesions. This approach reduces the need for a noninvasive stress test following the initial coronary angiogram and, possibly, a repeat procedure for stenting. After FFR or iFR assessment, immediate stenting, continued medical therapy, or referral to coronary artery bypass grafting (CABG) can be pursued based on the patient's characteristics and the coronary anatomy.

The main role of FFR or iFR at the time of catheterization is to prevent the need for subsequent stress testing and a separate procedure for stenting. In trials that evaluated the routine use of FFR in stable CAD, FFR had similar rates of death or MI but lower rates of repeat revascularization than angiography-guided revascularization. iFR-managed patients had similar rates of adverse events compared with FFR-managed patients:

●The FAME I trial was a prospective randomized trial that tested the hypothesis that FFR-guided percutaneous coronary intervention (PCI) would be superior to standard angiographic-guided PCI [22,31]. 1005 patients with multivessel CAD (at least two vessels with a ≥50 percent angiographic stenosis) were randomized to a strategy of FFR- or angiographic-guided PCI. The angiographic-guided group had a drug-eluting stent (DES) placed in all prospectively identified lesions, and the FFR-guided group had a DES placed only in lesions with an FFR of ≤0.80. The one-year rates of death (1.8 versus 3 percent in the angiographic group; relative risk [RR] 0.58, 95% CI 0.26-1.32) and MI (5.7 versus 8.7 percent; RR 0.66, 95% CI 0.42-1.04) were not clearly different between the two groups. The results after five years were similar.

●The FAME 2 trial compared the effectiveness of treating ischemic lesions (FFR ≤0.8) with optimal medical therapy (OMT) alone or with revascularization with PCI plus OMT [32]. 1220 patients with one-, two-, or three-vessel CAD suitable for PCI underwent FFR. All patients with lesions having FFR ≤0.8 were randomized to either PCI or OMT. There were no clear differences between those assigned to PCI or OMT on the outcomes of death or MI. The rate of urgent revascularization was lower in the PCI group (4.3 versus 17.2 percent). Patients with lesions with FFR >0.8 were entered into a registry; these patients had a low rate of death (0 percent), MI (1.8 percent), or urgent revascularization (2.4 percent) after 12 months of follow-up.

●The FAME 3 trial found that patients assigned to FFR-guided PCI had event rates similar to or possibly worse than patients assigned to CABG for treatment of three-vessel CAD in terms of death (1.6 versus 0.9 percent; hazard ratio [HR] 1.7, 95% CI 0.7-4.3) and MI (5.2 versus 3.2 percent; HR 1.5, 95% CI 0.9-2.5) [33]. After three years of follow-up, the rate of MI was higher among patients who underwent FFR-guided PCI (7.0 versus 4.2 percent; HR 1.7, 95% CI 1.1-2.7) [34].

●In two large trials (DEFINE-FLAIR and IFR-SWEDEHEART), the rates of composite outcomes were similar between iFR- and FFR-managed patients [10,11].

Acute coronary syndrome — In patients with STEMI or non-ST-elevation MI (NSTEMI), the hemodynamic significance of culprit lesions should be determined angiographically and not by measurement of FFR.

If there are nonculprit lesions of intermediate significance, FFR can be used to determine their ischemic potential. In the acute setting, nonculprit lesions with an abnormal FFR value are likely to be flow-limiting lesions, but normal readings may be false negatives. If FFR is performed more than four days after the index infarction, it is less likely to produce false negative results [35]. The general approach to nonculprit lesion revascularization is discussed elsewhere. (See "Acute coronary syndromes: Approach to nonculprit lesions".)

During the acute phase of infarction, there are dynamic changes in both the acute epicardial lesion and the distal microcirculation. In this state, resting flow, hyperemic flow, and microvascular function may be altered in the nonculprit artery, particularly when the nonculprit vessel is in proximity to the infarct zone. Changes in coronary flow related to acute myocardial injury affect both nonhyperemic pressure ratio (NHPR) and FFR measures.

Post-PCI assessment — FFR or an NHPR can be measured after PCI to obtain prognostic data, assess for residual stenosis, or assess diffuse disease, though this practice is not common [36-38]. There is some evidence to suggest that when stent placement is confirmed with intracoronary ultrasound, post-stenting FFR has no clear prognostic value [39].

Microvascular angina — The most appropriate flow measure for assessment of microvascular dysfunction is coronary flow reserve (CFR). The approach to diagnosis of microvascular angina is discussed in detail elsewhere. (See "Microvascular angina: Angina pectoris with normal coronary arteries", section on 'Diagnostic evaluation'.)

Surveillance in heart transplant recipients — In patients with heart transplantation, invasive and noninvasive CFR can be used to identify microvascular disease caused by coronary artery vasculopathy (CAV). The approaches to surveillance for and diagnosis of CAV in this setting are described separately. (See "Heart transplantation in adults: Cardiac allograft vasculopathy risk factors, surveillance, and diagnosis", section on 'Diagnosis'.)

SOCIETY AND GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic coronary syndrome".)

SUMMARY AND RECOMMENDATIONS

●Limitations of contrast angiography – The coronary angiogram may not accurately identify whether a specific lesion causes myocardial ischemia. This is particularly true among lesions with intermediate angiographic stenosis (30 to 70 percent diameter narrowing) (figure 1). (See 'Limitations of contrast angiography' above.)

●Intracoronary flow measurements – Measurement of a drop in pressure or drop in flow across a suspected coronary artery stenosis can be used to evaluate the ischemic potential of an intermediate coronary stenosis.

•Fractional flow reserve – Fractional flow reserve (FFR) is measured by comparing pressure beyond a suspicious coronary stenosis with pressure proximal to a coronary stenosis during hyperemia (ie, adenosine injection or infusion). An FFR measure ≤0.75 identifies a flow-limiting coronary stenosis likely to correlate with inducible ischemia on stress testing. (See 'Hyperemic pressure ratio, FFR' above.)

•Nonhyperemic pressure ratios – Nonhyperemic pressure ratios (NHPRs) are measured by comparing pressure beyond a suspicious lesion with pressure proximal to the lesion during diastole. The instantaneous wave-free ratio (iFR) is the most common NHPR measure, and iFR values ≤0.89 suggest the presence of a flow-limiting stenosis. (See 'Nonhyperemic pressure ratios (eg, iFR)' above.)

•Coronary flow reserve – Coronary flow reserve (CFR) is measured using an intracoronary wire that records flow either directly via thermodilution or indirectly via velocity (eg, Doppler) and compares hyperemic with basal flow. CFR should not be used to measure the severity of an epicardial coronary artery stenosis, since a concomitant abnormality of the microvascular circulation will produce an abnormal CFR. In patients without epicardial coronary artery disease (CAD) and suspected microvascular disease, CFR values <2.0 to 2.5 identify the presence of microvascular disease. (See 'CFR' above and "Microvascular angina: Angina pectoris with normal coronary arteries", section on 'Coronary flow reserve on angiography'.)

●Clinical scenarios

•Stable ischemic heart disease – In patients with angina despite maximal medical therapy who have not undergone a test for inducible ischemia but who proceed to invasive coronary angiography and are found to have coronary artery stenoses of intermediate severity (eg, 30 to 70 percent), it is reasonable to measure FFR or iFR at the time of coronary angiography to identify the ischemic potential of such lesions. This approach reduces the need for a noninvasive stress test following the initial coronary angiogram and, possibly, a repeat procedure for stenting. After FFR or iFR assessment, immediate stenting, continued medical therapy, or referral to coronary artery bypass grafting (CABG) can be pursued based on the patient's characteristics and the coronary anatomy. (See 'Stable ischemic heart disease' above.)

•Acute coronary syndrome – In patients with ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI), the hemodynamic significance of culprit lesions should be determined by angiography and not by measurement of FFR. If there are nonculprit lesions of intermediate significance, FFR can be used to determine their ischemic potential. In the acute setting, nonculprit lesions with an abnormal FFR value are likely to be flow-limiting lesions, but normal readings may be false negatives. (See 'Acute coronary syndrome' above and "Acute coronary syndromes: Approach to nonculprit lesions", section on 'Assessment of nonculprit lesion anatomy'.)

•Diagnosis of microvascular angina – The most appropriate flow measure for assessment of microvascular dysfunction is CFR. The approach to diagnosis of microvascular angina is discussed in detail elsewhere. (See "Microvascular angina: Angina pectoris with normal coronary arteries", section on 'Diagnostic evaluation'.)

•Surveillance after heart transplantation – In patients with heart transplantation, invasive and noninvasive CFR can be used to identify microvascular disease caused by coronary artery vasculopathy (CAV). The approaches to surveillance for and diagnosis of CAV in this setting are described separately. (See "Heart transplantation in adults: Cardiac allograft vasculopathy risk factors, surveillance, and diagnosis", section on 'Diagnosis'.)