Clinical use of coronary artery pressure flow measurements

INTRODUCTION — Myocardial revascularization with either percutaneous coronary intervention or coronary artery bypass graft surgery is indicated when there is documentation of significant obstruction to coronary blood flow associated with myocardial ischemia in patients for whom medical therapy is expected to lead to suboptimal outcomes. In most cases, coronary artery stenoses with greater than 80 percent diameter reduction as seen on coronary angiography are associated with myocardial ischemia, the extent of which may or may not have been assessed with prior noninvasive testing.

In some patients, the coronary angiogram demonstrates one or more lesions that are not severely stenosed or appear hemodynamically "benign." For lesions associated with narrowing in the range of 40 to 80 percent diameter reduction [1,2], also called intermediate severity stenoses, obtaining coronary artery physiologic data, usually coronary artery pressure and flow, can facilitate clinical decision making regarding need for revascularization, particularly in individuals without noninvasive stress test documentation of myocardial ischemia (figure 1).

TECHNICAL ASPECTS — Sensor tipped angioplasty guidewires have been developed and are used to measure pressure and flow across a coronary stenosis in the catheterization lab [3-8]. The use of coronary pressure guidewires is generally safe and typically adds a few minutes to the total procedure time for the assessment of each lesion.

Fractional flow reserve (FFR) measures the pressures proximal to (aortic pressure) and distal to (guidewire pressure) stenotic lesions at maximal flow and creates a pressure ratio, representing the proportion of flow across that stenosis (waveform 1). For accurate FFR measurements, pressures obtained during hyperemia are required. Maximal blood flow (hyperemia) is most commonly induced by intravenous (140 mcg/kg/min) or intracoronary adenosine (right coronary artery 50 to 100 mcg, left coronary artery 100 to 200 mcg bolus). The ratio of distal coronary pressure to aortic pressure (as recorded from the guide catheter) during maximal hyperemia is called the FFR. A normal value is 1, while values <0.80 are associated with provocable ischemia with an accuracy >90 percent [9]. The occurrence of false negative and false positive FFR values is rare.

FFR measurements in intermediate severity lesions have some inherent limitations. Both false positive and negative FFR values are uncommon but exist. The most common reasons to have a false negative FFR (ie, a high FFR) is guide catheter pressure damping (preventing flow into the vessel), failure to induce hyperemia (wrong concentration, poor intravenous infusion), or acute coronary syndrome with an impaired myocardial bed acutely that then improves over time. The initially high FFR, while not truly false, may be lower after the bed and the myocardial flow improve.

False positive FFR values are the result of technical failures due to inaccurate calibrations, guidewire signal drift downward, or aortic pressure drift upward.

In addition to obstructive focal lesions, flow to the myocardium can be impaired by the presence of diffuse atherosclerotic disease or microcirculatory dysfunction. Other measurements of coronary flow, such as the coronary flow reserve and the index of microcirculatory resistance, have been evaluated as tools for assessing the microcirculation [10]. The role of these measures in clinical practice has not been established.

An adenosine-independent, resting pressure-derived index of coronary stenosis severity has been developed and tested as a substitute for FFR. Using wave intensity analysis [11], it was determined that the period of diastole in which equilibration or balance between pressure waves from the aorta and distal microcirculatory reflection was a "wave-free period" met the requirements of FFR to have minimal and constant coronary resistance (figure 2A-B). Pd/Pa during the wave-free period (75 percent into diastole ending 5 msec before the R wave) is called the instantaneous wave-free pressure ratio (iFR). It was demonstrated that at iFR cut-points of >0.93 or <0.86, there was a strong correlation with normal and abnormal FFR values (using 0.80 as an FFR cut point). In the ADVISE II study [12], iFR was compared to FFR in 690 intermediate stenoses. Compared to FFR (<0.80), iFR cut-off of 0.89 correctly classified 83 percent of stenoses. iFR correctly classified those stenoses outside the 0.85 to 0.94 iFR gray zone with 92 percent agreement. Thus, the hybrid iFR-FFR approach to intermediate stenosis could be assessed without the need for hyperemic stimulus in 65 percent of patients. iFR is compared to FFR below.

IFR COMPARED WITH FFR — Until additional studies confirm the benefit from instantaneous wave-free pressure ratio (iFR), a newer technique, we use either iFR or fractional flow reserve (FFR) for evaluation of intermediate coronary artery lesions. (See 'Technical aspects' above.)

Two randomized, noninferiority trials in low-risk patients have evaluated clinical outcomes in patients with stable or unstable disease who had one or more coronary artery lesions for which physiologic assessment prior to revascularization was indicated [13,14]. In these two studies, single cut points for iFR and FFR were chosen at 0.89 and 0.80, respectively (figure 3):

●In the iFR SWEDEHEART study, 2037 patients were randomly assigned to iFR or FFR [13]. The primary end point, a composite of death from any cause, nonfatal myocardial infarction (MI), or unplanned revascularization within 12 months occurred with equal frequency (6.7 versus 6.1 percent; difference in event rates, 0.7 percentage points, 95% CI -1.5 to 2.8; hazard ratio 1.12, 95% CI 0.79-1.58).

●In the DEFINE-FLAIR trial, 2492 patients were randomly assigned to iFR or FFR [14]. At one year, the primary end point, a composite of death from any cause, nonfatal MI, or unplanned revascularization, occurred with equal frequency (6.8 versus 7.0 percent; difference in risk, 0.2 percentage points, 95% CI -2.3 to 1.8; hazard ratio 0.95, 95% CI 0.68-1.33).

In these two studies, fewer patients in the iFR group had adverse procedural symptoms/clinical signs (related to adenosine administration) and the median procedural time was shorter.

COMPARISON WITH OTHER DIAGNOSTIC TECHNIQUES — Fractional flow reserve (FFR), described above, is the clinical standard for the invasive physiologic assessment of the severity in intermediate stenoses. For clinical decision-making regarding cases in which the hemodynamic impact of a lesion(s) is in question, FFR is superior to intravascular ultrasound (IVUS). FFR may be superior to noninvasive stress radionuclide myocardial perfusion imaging (rMPI) in patients with multivessel coronary artery disease. (See 'Intermediate severity stenosis' below.)

Magnetic resonance myocardial perfusion imaging (MRMPI), with intravenous adenosine and a first-pass gadolinium bolus, has been shown to correlate well with FFR in detecting reversible ischemia. When tested against an FFR <0.75 in 103 patients with angina (300 coronary artery segments), MRMPI had a high sensitivity (91 percent), specificity (94 percent), positive predictive value (91 percent), and negative predictive value (94 percent) for detecting functionally significant coronary heart disease [15].

Unlike MRMPI, single-photon emission computed tomography (PET-CT) myocardial perfusion imaging showed poor concordance with FFR in identifying ischemic territories. In a study of 67 patients (201 vascular territories) with angiographic 2v or 3v coronary disease, PET-CT and FFR detected identical ischemic territories in only 42 percent of patients. In the remaining patients, PET-CT tended to significantly underestimate or overestimate the number of ischemic regions compared to FFR [16].

Conflicting data when noninvasive stress imaging such as nuclear perfusion imaging and FFR produce different results produces uncertainty in the mind of the clinician. In such cases, the clinician must re-evaluate his or her level of confidence in the accuracy of both test modalities. For nuclear perfusion imaging, there are a number of common conditions producing false positive and false negative results. For FFR, there are rare situations producing false positive and almost none producing false negative results. The use of FFR is not indicated when the clinical picture, angiogram, and stress test are concordant. Otherwise, the FFR may alleviate uncertainty when the clinical and testing data are at odds with one another. The use of FFR is based on its ability to precisely define the ischemic potential of a stenosis in question.

IVUS, a standard for intravascular anatomic information has attempted to establish a physiologic correlation to anatomic dimensions. In a prospective registry of 350 patients with 367 intermediate coronary lesions (40 to 80 percent by angiography), anatomic measurements by IVUS showed only a moderate correlation with FFR values [17]. IVUS is best used in assessing lesions appropriate to defer when minimal lumen area exceeds the area under the curve threshold but cannot be relied upon to accurately identify which lesions should be treated. Further study is needed prior to our recommending IVUS for this purpose. (See "Intravascular ultrasound, optical coherence tomography, and angioscopy of coronary circulation", section on 'Intravascular ultrasound'.)

IVUS and optical coherence tomography (OCT) provide a high degree of anatomic detail useful in making clinical decisions. Although the cross-sectional lumen area (ie, minimal luminal area or MLA) measured by these techniques has been proposed as a surrogate measurement of the functional significance of a given stenosis, the correspondence with FFR has been only moderate. FFR is a physiologic assessment, whereas IVUS/OCT are highly accurate for vessel sizing and confirming stent expansion and strut apposition. The poor correlation between MLA and FFR can be understood from review of the factors that produce pressure loss across a stenosis.

In a report of 25 IVUS or OCT imaging studies correlated to FFR, the best cut-off value (BCV) for MLA ranged from 1.8 to 4.0 mm² (excluding the left main BCVs of 4.8 to 5.9 mm²) with areas under the curve ranging from 0.63 to 0.90 [18]. However, while it is true that MLA >4 mm² had FFR> 0.8 in 91 percent of cases with a strong negative correlation, an MLA <4 mm² had poor correlation to FFR, with most studies reporting a roughly 50 percent chance of having an FFR <0.8 [19].  

rMPI and FFR have been compared in patients with stable angina [7,8,20], non-ST elevation acute coronary syndrome [21], and chest pain of uncertain origin [9]:

●Stable angina – Early studies showed a high correlation between abnormal coronary vasodilator reserve and either ischemia [8] or future cardiac events [20]. However, subsequent studies have shown that, compared to FFR, rMPI has a poor correlation because of the confounding influence of multivessel disease and variable intensity of ischemia needed to produce an important perfusion defect [22].

●During and shortly after an acute myocardial infarction (MI), transient microvascular dysfunction impairs maximal coronary hyperemia and limits the accuracy of FFR for both culprit and non-culprit lesion assessment. In acute coronary syndrome (ACS), diffuse microvascular impairment may falsely elevate the FFR. Therefore, in this setting, a low FFR indicates true hemodynamic significance but a normal FFR may not be definitive. FFR of 112 non-culprit lesions was measured during an acute MI (75 patients with ST elevation MI, 26 patients with non-ST elevation MI) and again 35 ± 24 days later [23,24]. Only two lesions had a clinically meaningful change where FFR was >0.80 during the acute episode and <0.75 at follow-up. Trials that have evaluated the use of FFR in ACS are summarized in a table. These studies show that when used appropriately, FFR can be a useful tool in assessing patients after an acute MI.

●Non-ST elevation ACS – In an analysis of 70 patients presenting with a non-ST elevation ACS, myocardial FFR was as effective as rMPI for detecting significant lesions [21]. These patients, who had a single coronary lesion of moderate severity at catheterization within 48 hours of presentation, were randomly assigned to undergo FFR measurement or rMPI; those in the FFR group were discharged if the FFR was ≥0.75, while those in the perfusion imaging group were discharged if the study revealed no evidence of ischemia. At one year, the following findings were noted:

•No deaths had occurred in either group

•The rates of angina, myocardial infarction, and coronary artery bypass graft surgery were the same in both groups.

•The duration of hospitalization was significantly shorter for the FFR group (11 versus 49 hours)

INTERMEDIATE SEVERITY STENOSIS — A stenosis of intermediate severity, defined as a >40 to <80 percent diameter narrowing as assessed by visual inspection of the radiocontrast luminogram during coronary angiography, is encountered in almost 50 percent of patients undergoing coronary arteriography. However, there are significant limitations to visual inspection that impact the ability of the observer to predict the hemodynamic impact of these lesions. Measurement of fractional flow reserve (FFR) is useful to evaluate the clinical significance of lesions in this range, particularly when there is no prior noninvasive documentation of myocardial ischemia. From time to time, even more angiographically severe lesions may benefit from FFR.

FFR measurements (figure 4 and waveform 2A-C) can identify which of these lesions are hemodynamically significant, thereby assisting in immediate decision making. Multiple studies have shown that percutaneous coronary intervention (PCI) of intermediate lesions can be safely deferred if the FFR is above the non-ischemic value (ie, >0.75) [4,25-29]. This approach has been applied in patients with single or multivessel disease [25,30,31].

The impact of the routine use of FFR in patients with at least one angiographically ambiguous lesion (35 to 65 percent by visual estimate) was evaluated in a registry study of 1075 (80 percent stable) patients undergoing diagnostic coronary angiography [32]. The study design mandated that investigators prospectively define their revascularization strategy based on angiography (before FFR). The following findings were noted:

●The strategy after angiography (but before FFR) was medical therapy in 55 percent, PCI in 38 percent, and coronary artery bypass graft surgery (CABG) in 7 percent.

●After FFR, which drove decision making in 96 percent of cases, the strategy was medical therapy in 58 percent, PCI in 32 percent, and CABG in 10 percent. However, the final strategy reclassified 43 percent of cases, with some moving from medical therapy to revascularization and others in the opposite direction.

●The occurrence of a major cardiac event (death, MI, or unplanned coronary revascularization) at one year was similar in the 464 reclassified patients to those who were not reclassified (11.2 versus 11.9 percent).

Additional support for the routine use of FFR comes from a retrospective study of 7358 patients scheduled to undergo PCI [33]. Among these, 6268 did not undergo FFR measurement and 1090 did. During a median follow-up of about 51 months, there were significantly more major adverse cardiac events (a composite of death, myocardial infarction, and any revascularization) in the no-FFR group (57 versus 50 percent; p = 0.016).

Patients needing CABG — The issue of whether the use of FFR to evaluate intermediate lesions can improve outcomes in patients who will be referred for CABG has been evaluated in one observational study [34]. Among 627 patients having at least one angiographically intermediate stenosis, 429 had bypass grafts placed based on angiographic findings only, and 198 based on FFR (bypass of a lesion was deferred if the FFR was >0.80). At three years, major adverse cardiovascular events (a composite of overall death, myocardial infarction, and target vessel revascularization) were similar between the two groups (12 versus 11 percent; hazard ratio 1.03, 95% CI 0.67-1.69). The rate of angina was significantly lower in the FFR-guided group (31 versus 47 percent), despite fewer venous grafts being placed.

While the surgical practice of grafting all vessels with angiographic stenosis of >50 percent has been a long-standing standard, CABG of vessels with hemodynamically non-significant stenosis has a higher rate of graft closure compared with those vessels with severe stenosis [35], who prospectively studied 525 lesions in 153 patients referred for bypass surgery. FFR was performed on all lesions to be grafted, with the surgeon blinded to the results. Repeat angiogram performed one year after CABG showed that 21.4 percent of grafts on functionally non-significant lesions (FFR >0.75) were occluded, compared with 8.9 percent of grafts on vessels with FFR <0.75. Although the highest percentage of occluded grafts was found in the group placed on vessels with <50 percent stenosis, there was still a high percentage of graft failure in the group with 50 to 70 percent stenosis with a variable relationship to FFR. In this study, FFR-guided bypass has superiority over the strategy of grafting all vessels with lesions with 50 percent or more stenosis.

FFR-guided bypass was compared with angiographically-guided bypass surgery in a retrospective review of 627 patients with stable coronary artery disease referred for CABG with at least one angiographically intermediate stenosis. In 31 percent of patients, FFR had been performed to determine whether an intermediate stenosis should be grafted or not [34]. In this group, the incidence of three-vessel disease was downgraded after FFR from 94 to 86 percent, and use of FFR was associated with a smaller number of anastomoses and rate of on-pump surgery. At three years, there was no difference in adverse events compared with those patients who underwent angiography-guided CABG, and the rate of angina was lower in the FFR group (31 versus 47 percent, p<0.001), possibly owing to a higher ratio of arterial to venous anastomosis.

DIFFUSE DISEASE AND LONG LESIONS — Patients, particularly those with diabetes, may have diffuse disease and/or one or more coronary arteries with long lesions. The clinical impact of these lesions may be uncertain as they may be associated with no tight stenoses. Fractional flow reserve (FFR) measurements can be useful in decision-making regarding the location for optimal percutaneous coronary intervention (PCI) within a given artery, or even the need for coronary artery bypass graft surgery as an alternative to PCI.

To study the significance of abnormalities along a diseased coronary artery, the pressure wire can be pulled back slowly during hyperemia, precisely indicating at which particular locations hemodynamically significant abnormalities are present. To obtain a pullback recording, the sensor is placed in the distal segment of the coronary artery and sustained maximum hyperemia is induced either by intravenous adenosine (140 mcg/kg/min) or rarely intracoronary Papaverine (10 to 12 mg). The sensor is then pulled back slowly by hand under fluoroscopic guidance, recording the pressure curves at the same time. Pressure gradients and FFR at various segments over the length of the artery are calculated. Pressure loss due to diffuse atherosclerosis is gradual, whereas a focal stenosis can be differentiated by an abrupt increase in pressure proximal to the lesion. By moving the sensor back and forth, the exact location of a pressure drop representing a focal obstruction to flow can be determined [36,37].

STENTED SIDE BRANCHES — The clinical importance of jailed side branches after stenting of a parent vessel is a concern. (See "Percutaneous coronary intervention of specific coronary lesions", section on 'Bifurcation lesions'.)

This issue has been evaluated with physiologic assessment of jailed side branches using fractional flow reserve (FFR) and comparing it to stenosis severity using quantitative coronary angiography [38]. Ninety-seven jailed side branch lesions in vessels >2.0 mm with a percent stenosis >50 percent by visual estimation after stent implantation underwent FFR in the main vessel and side branches. In 94 lesions, the mean FFRs were 0.94+/-0.04 and 0.85+/-0.11 at the main branches and jailed side branches, respectively. There was a significant negative correlation between the percent stenosis and FFR (r = -0.41). However, no lesion with <75 percent stenosis had FFR <0.75. Among 73 lesions with >75 percent stenosis, only 20 lesions were functionally significant. FFR across jailed side branch lesions suggests that most of these lesions do not have functional significance.

MULTIVESSEL DISEASE — The practice of attempting complete or near complete revascularization in the catheterization laboratory for patients with symptomatic coronary artery disease has become more frequent. However, this approach has not been shown to be associated with better outcomes in some studies. (See "Percutaneous coronary intervention of specific coronary lesions", section on 'Multivessel revascularization'.)

Attempts to identify which arteries need to be revascularized by demonstrating myocardial ischemia have been made using both noninvasive and invasive techniques. However, noninvasive assessment of myocardial ischemia with radionuclide myocardial perfusion imaging may not accurately identify the severity of any given lesion in this setting.

The potential role for the measurement of fractional flow reserve (FFR) of all angiographically significant lesions before planned PCI was evaluated in the FAME trial [31]. After diagnostic angiography, 1005 patients with multivessel coronary artery disease were assigned to strategies of either stenting of all indicated lesions (≥50 percent diameter stenosis) with drug-eluting stents or to FFR-guided percutaneous coronary intervention (PCI) only of those lesions with an FFR ≤0.80. At one year, the following findings were noted:

●The primary end point of the rate of all-cause death, nonfatal MI, and repeat revascularization occurred significantly less often in the group who underwent FFR-guided PCI (13.2 versus 18.3 percent). This was driven by lower rates of myocardial infarction (5.7 versus 8.7 percent) and revascularization (6.5 versus 9.5 percent).

●The mean number of stents was significantly lower in the FFR group (1.9 versus 2.7 percent).

●Approximately 80 percent of patients in both groups were free of angina at one year. While we do not advocate FFR of all potentially hemodynamically important lesions, this study adds further evidence to support its use for lesions of moderate severity.

At two years, the rate of death or MI was lower in the FFR group (8.4 versus 12.9 percent; p = 0.02) [39]. At five years, the primary end point of major adverse cardiac events was similar in the two groups (28 versus 31 percent; relative risk 0.91, 95% CI 0.75-1.10) [40]. In addition, the number of stents placed per patient was significantly lower in the FFR group (1.9 versus 2.7; p <0.0001). We believe these results from long-term follow-up of FAME patients support the use of FFR in appropriately selected patients.

The FAME II trial compared PCI with optimal medical therapy (OMT) to OMT in patients with at least one lesion with an FFR of <0.80. This trial is discussed elsewhere. (See "Chronic coronary syndrome: Indications for revascularization".)

LEFT MAIN AND OSTIAL LESIONS — Angiographic evaluation of the ostium of the major epicardial coronary arteries and their major side branches is often suboptimal due to overlap from the parent vessel or difficult orientation of the vessel in relation to achievable camera positions. The clinical significance of an ostial stenosis may be better evaluated with fractional flow reserve, which may be particularly beneficial in patients with left main disease [41,42].

The left main coronary artery (LMCA) stenosis is among the most difficult lesions to interpret angiographically and among the most critical of clinical presentations. LMCA stenosis may involve the aortic-ostial junction, mid-body, or distal LM, which may involve the left anterior descending (LAD)/circumflex ostia. When assessing ostial LM narrowing by fractional flow reserve (FFR), care is needed to avoid guide catheter damping by disengaging the guide from the ostium and using intravenous rather than intracoronary adenosine to achieve consistent hyperemia. In case of a distal narrowing of the LMCA, this procedure may be performed twice, once with the pressure wire in the LAD artery and then again in the circumflex artery.

Numerous studies support FFR for assessment of left main coronary stenoses. In the largest of such studies [43], five-year outcomes were examined in 213 patients with an angiographically equivocal left main coronary artery stenosis in whom revascularization decisions were guided by FFR. When FFR was ≥0.80, patients were treated medically or another stenosis was treated by coronary angioplasty (nonsurgical group; n = 138). When FFR was <0.80, CABG surgery was performed (surgical group; n = 75). The five-year survival and event-free survival rates were similar with 90 and 74 percent in the nonsurgical (FFR ≥0.80) group and 85 and 82 percent in the surgical (FFR <0.80) group (p = 0.48).

Noteworthy was that only 23 percent of patients with LM >50 percent diameter stenosis had a hemodynamically significant FFR.

FFR in LMCA lesions with downstream disease (eg, LAD lesions) requires an understanding of serial lesions and how they affect one another. The myocardial bed flow for the LM is the sum of both the LAD and circumflex territories and this flow determines the LM FFR. In the presence of a significant LAD stenosis, flow in the LAD territory may be reduced, reducing total LM flow and hence falsely increasing the apparent LM FFR value. The higher “apparent” LM FFR is only a concern if either the LAD or circumflex are severely hemodynamically impaired (FFR of LM and LAD <0.6) [44]. For serial LM with downstream LAD disease, when FFR beyond LAD is <0.60, the apparent LM FFR may be questioned. In this case, IVUS assessment with a threshold of <6.0 mm² is recommended.

UNDER DEVELOPMENT — Methods to estimate the fractional flow reserve (FFR) from angiographic reconstructions have emerged for computed tomographic angiography. Based on computation fluid dynamic principles, the three-dimensional reconstructed angiographic images coupled with input assumptions of myocardial flow and bed resistance yield fairly strong correlations (approximately 80 percent agreement) between angiographically-derived and pressure-wire-measured FFR. In a meta-analysis of 13 studies assessing the diagnostic performance of angiography-derived FFR using different several computational models, a pooled sensitivity of 89 percent and specificity of 90 percent with a positive likelihood ratio of 9.3 (95% credible interval 7.3-11.7) and negative likelihood ratio of 0.13 (95% credible interval 0.07-0.2) were found [45]. The analysis did not find differences between the methods for pressure-drop calculation. The accuracy of angiography-derived FFR was good enough to reliably detect hemodynamically significant lesions determined with pressure wire. Given the early results of angiographically-derived FFR coupled with the ability to employ future novel indices (eg, Wall shear stress), the future of coronary artery disease assessment will likely be "wireless."  

POST-PROCEDURE FFR AND PROGNOSIS — Coronary pressure measurements after stenting predict adverse cardiac events at follow-up. Post-procedural fractional flow reserve (FFR) was used in a study of 750 patients and used these findings to predict major adverse cardiac events at six months [46]. In 76 patients (10.2 percent), at least one adverse event occurred. Five patients died, 19 experienced myocardial infarction, and 52 underwent at least one repeat target vessel revascularization. FFR immediately after stenting was an independent variable related to all types of events. In 36 percent of patients, FFR normalized (>0.95), with an event rate of 5 percent. In 32 percent of patients with post-FFR between 0.90 and 0.95, event rate was 6 percent. In the remaining 32 percent with FFR less than 0.90, event rates were 20 percent. In 6 percent of patients with FFR less than 0.80, the event rate was 30 percent.    

RECOMMENDATIONS OF OTHERS — The 2012 American College of Cardiology Foundation/American Heart Association/American College of Physicians/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society for Cardiac Angiography and Intervention/Society of Thoracic Surgeons guideline for the diagnosis and management of patients with stable ischemic heart disease supported the use of the measurement of fractional flow reserve to determine whether percutaneous coronary intervention (PCI) of a specific coronary lesion is warranted [47]. The 2014 European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines on myocardial revascularization made a stronger recommendation for fractional flow reserve-guided PCI in patients without prior noninvasive documentation of evidence of vessel-related ischemia [48]. They also make a weak recommendation for fractional flow reserve-guided PCI in patients with multivessel disease.

SUMMARY AND RECOMMENDATIONS

●Coronary artery lesions, as seen on coronary angiography, that are neither critically stenosed nor minimally narrowed (ie, nonsignificant) are referred to as “intermediate stenoses” and are typically reported to have narrowing (diameter reduction) in the range of 40 to 80 percent. (See 'Introduction' above.)

●Fractional flow reserve (FFR) is the clinical standard for the invasive physiologic assessment of the hemodynamic significance (ie, ischemic potential) of intermediate stenoses. For clinical decision making regarding cases in which the hemodynamic impact of a lesion(s) is in question, FFR is superior to intravascular ultrasound and in many cases to noninvasive stress radionuclide myocardial perfusion imaging. (See 'Comparison with other diagnostic techniques' above.)

●For intermediate stenoses where there is a question of whether revascularization should be carried out, and there are no prior useful noninvasive physiologic data to guide decision making, FFR should be measured before the decision to implant a stent. (See 'Intermediate severity stenosis' above.)