Fractional Flow Reserve
A Useful Index to Evaluate the Influence of an Epicardial Coronary Stenosis on Myocardial Blood Flow
Background Fractional flow reserve (FFR), defined as the ratio of maximum flow in the presence of a stenosis to normal maximum flow, is a lesion-specific index of stenosis severity that can be calculated by simultaneous measurement of mean arterial, distal coronary, and central venous pressure (Pa, Pd, and Pv, respectively), during pharmacological vasodilation. The aims of this study were to define ranges of FFR values, whether associated with inducible ischemia or not, and to investigate FFR in normal coronary arteries.
Methods and Results In 60 patients accepted for percutaneous transluminal coronary angioplasty (PTCA) of single-vessel disease, with a positive exercise test (ET) <24 hours before PTCA, FFR was determined during adenosine-induced hyperemia just before and 15 minutes after angioplasty. Pa was measured by the guiding catheter, Pd by an 0.018-in fiber-optic pressure-monitoring wire, and Pv by a multipurpose catheter. The ET was repeated after 5 to 7 days, and only if this second ET had reverted to normal was the pre-PTCA value of FFR definitely considered to be associated with inducible ischemia and the post-PTCA value not.
Myocardial FFR (FFRmyo) increased from 0.53±0.15 before PTCA to 0.88±0.07 after PTCA. Coronary FFR increased from 0.38±0.19 to 0.83±0.12. In all patients, values of FFRmyo definitely associated with ischemia were ≤0.74, whereas all except two values not associated with inducible ischemia exceeded 0.74. Moreover, FFRmyo in 18 coronary arteries in 5 normal patients equaled 0.98±0.03.
Conclusions A value of FFRmyo of 0.74 reliably discriminates coronary stenosis, whether associated with inducible ischemia or not. Therefore, FFRmyo is a useful index to determine the functional significance of an epicardial coronary stenosis and may facilitate clinical decision making in patients with an equivocal coronary stenosis.
The fundamental limitations of coronary angiography and its poor correlation with functional stenosis severity in terms of blood flow obstruction are well recognized.1 2 Therefore, many methods have been proposed to directly measure flow, flow reserve, or other flow indexes.3 However, a common problem in the interpretation of classic flow indexes has been the variation of normal values and thus the overlap between normal and pathological values.4 5 6 7 8 This variation is due in part to the dependency of those indexes on hemodynamic loading conditions and negligence of collateral blood flow.9 10 11
Recently, we introduced the concept of FFR, defined as maximum achievable blood flow in the presence of a stenosis divided by maximum flow if there was no obstructive epicardial coronary disease at all.12 13 FFR, therefore, is a lesion-specific index reflecting the effect of the epicardial coronary stenosis on myocardial perfusion.
Features of FFR are its independence of pressure changes, its simple derivation from pressure recordings, and at least to some extent, its inclusion of the contribution of collateral flow to total myocardial perfusion. Moreover, because normal FFR is well defined and theoretically equal to 1 for every patient, every coronary artery, and every myocardial distribution, a diminished value of FFR can be interpreted without the necessity of a normal reference distribution. Calculation of FFR by pressure measurements has a sound scientific basis and has been validated in animals and humans.12 13 However, before FFR can be used for clinical decision making, such as whether to perform revascularization in patients with equivocal coronary stenosis, it is mandatory to investigate whether clear, well-defined ranges of “pathological” and “nonpathological” values of FFR exist. The first aim of this study was to investigate whether such well-demarcated ranges of FFR values do exist and, if so, to define them. The second aim was to test the assumption that in normal human coronary arteries, FFR equals 1.0 and that no significant resistance to flow is provided by normal large epicardial coronary arteries.
PTCA patients. The first group of our study population (group A) consisted of 60 consecutive patients (41 men, 19 women; age, 57±8 years; range, 39 to 74 years) accepted for elective PTCA with stable angina pectoris, single-vessel coronary disease (left anterior descending coronary artery, 39; left circumflex artery, 8; and right coronary artery, 13), normal left ventricular function, and a clearly positive ET <24 hours before PTCA. Exercise testing in these patients was performed on an bicycle ergometer starting with a workload of 20 W that was increased by 20 W every minute. The test was considered positive when ST-segment depression of ≥1 mm occurred 80 ms after the J-point in at least two adjacent leads.
At the PTCA, FFR was determined before and after balloon dilatation according to the protocol described below. After successful PTCA, all medication was stopped except nifidepine 20 mg BID, which was stopped 48 hours later, and aspirin 80 mg/d, which was continued. The ET was then repeated 5 to 7 days after the PTCA. Only if this second ET was completely normal was it claimed that the pre-PTCA value of FFR was compatible with inducible ischemia and the post-PTCA value was not. If the second ET was still positive, coronary arteriography, including determination of FFR, was repeated within 10 days to confirm or exclude early restenosis.
Patients with normal coronary arteries. Group B consisted of 5 patients (4 men and 1 woman; 55, 58, 60, 56, and 50 years old) without cardiovascular risk factors who had visited the outpatient clinic within the previous year because of atypical chest pain and who had a normal coronary angiogram. After informed consent had been obtained, these individuals underwent exercise testing, 201Tl scintigraphy, and dobutamine stress echocardiography. After it had been concluded that all these tests were normal, coronary angiography was repeated and FFR was determined in all large coronary arteries and side branches as described below. Informed consent was obtained for all procedures, and the study protocol was approved by the Institutional Review Board of the Catharina Hospital.
Catheterization Protocol and Pressure Measurements
Group A: PTCA patients. A 7F sheath was introduced into the femoral vein, and a 6F multipurpose catheter was placed into the right atrium for recording of Pv. A 6F to 8F guiding catheter was introduced into one femoral artery, and after administration of 10 000 U heparin IV, this catheter was advanced into the ostium of the coronary artery. Pa was monitored by this guiding catheter. Nitroglycerin 0.5 mg SL was administered and repeated every 30 minutes. Angiograms of the target vessel were then obtained as usual.
To measure Pd, an 0.018-in fiber-optic high-fidelity pressure-monitoring wire was used (Pressure-guide, Radi Medical). This fiber-optic pressure wire has been described previously14 15 and is shown in Fig 1⇓. After calibration, this fiber-optic wire was introduced into the guiding catheter and advanced to its tip. At that point, equality of pressures registered by the guiding catheter and the fiber-optic wire was verified (Fig 2A⇓).
The wire was then advanced into the coronary artery and positioned across the stenosis (Fig 2B⇑). Pa, Pd, and Pv were monitored continuously during the procedure. After the pressures had stabilized, maximum coronary hyperemia was obtained by intravenous adenosine (140 μg·kg−1·min−1) infused through the side arm of the venous sheath.16 Fig 2C⇑ shows the further decrease of distal coronary pressure associated with maximum hyperemia. From the simultaneous recording of Pa, Pd, and Pv at steady-state maximum hyperemia, FFRmyo before PTCA was calculated as described below.
After adenosine infusion was stopped, an adequate balloon catheter with an 0.018-in central lumen was advanced over the fiber-optic wire, and then angioplasty was performed. During the balloon inflations of 2 minutes each, Pa, Pd (then called Pw), and Pv were also continuously recorded (Fig 2D⇑). Fifteen minutes after a satisfactory angiographic result had been obtained, adenosine infusion was started again for post-PTCA recording of Pa, Pd, and Pv at maximum hyperemia. This allowed calculation of the post-PTCA value of FFR (Fig 2F⇑). Finally, the fiber-optic wire was withdrawn into the guiding catheter, and equality of both pressures was rechecked for drift (Fig 2G⇑). Patients were discharged 2 days later as usual.
Group B: Patients with normal coronary arteries. Preparation of the catheters and the pressure wire was similar to group A. The fiber-optic wire was then carefully advanced into all easily accessible large coronary arteries up to the most distal third. If the coronary arteries were tortuous, positioning of the fiber-optic wire was performed with the help of a 3F multifunctional probing catheter (Schneider AG). Steady-state hyperemia was then induced as previously described, and Pa, Pd, and Pv were recorded simultaneously. Myocardial FFR for the dependent bed of the artery was then calculated. An example of such a recording is shown in Fig 3⇓.
Calculation of FFR
FFRcor is defined as the maximum coronary flow in the presence of a stenosis divided by the normal maximum flow of the artery (ie, the maximum flow in that artery if no stenosis were present). Similarly, FFRmyo is defined as maximum myocardial blood flow distal to an epicardial stenosis divided by its value if no epicardial stenosis were present. Stated another way, FFR represents that fraction of normal maximum flow that remains despite the presence of an epicardial lesion. As published earlier, the FFR of a coronary artery and its dependent myocardium can be calculated by
where Pa, Pd, and Pv are taken at maximum vasodilation. Pw is taken at coronary occlusion.12 13 Because of the necessity to know Pw, FFRcor can be calculated only during PTCA. FFRmyo, however, can also be calculated during diagnostic procedures. The difference between FFRmyo and FFRcor represents the contribution of collateral flow to total myocardial perfusion and is called fractional collateral flow.12 13 17 Because FFRmyo reflects both antegrade and collateral contribution to maximum myocardial perfusion, it is the most important flow index from a clinical point of view. It describes to what extent maximum myocardial perfusion is affected by the epicardial coronary stenosis, as will be discussed later.
Quantitative Coronary Angiography and Data Analysis
In the patients with normal angiograms, the diameters of all coronary artery branches were determined at their respective origins and the at site of distal intracoronary pressure measurement by use of the CAAS system.18 The values presented are the averages of two orthogonal projections and are expressed as mean±SD.
Procedural and Clinical Results
No complications occurred due to the specific study protocol in any of the patients from both groups.
In 41 of the 60 PTCA patients, the stenosis could be easily reached and successfully crossed by the fiber-optic wire without additional equipment. In the remaining 19 PTCA patients, the stenosis first had to be crossed by a regular 0.014-in high-torque floppy guide wire (Advanced Cardiovascular Systems Inc), which was subsequently exchanged for the fiber-optic wire.
In all patients, excellent pressure signals were obtained before and after PTCA. In 7 patients, no reliable Pw could be recorded during balloon inflation. In one PTCA patient, a large dissection with occlusion of the proximal left anterior descending artery occurred after the second balloon inflation, and emergency bypass surgery was necessary. In another patient, no satisfactory angiographic result could be obtained despite many inflations. Because of recurrent angina at rest 2 days later, bypass surgery was performed, and no post-PTCA ET was available. Therefore, in our group of 60 PTCA patients who fulfilled the primary inclusion criteria, an angiographically successful result was obtained in 58 patients, and 56 had a normal ET 5 to 7 days after the PTCA. Therefore, on the basis of bayesian considerations, it can be stated that inducible ischemia had been present in these 56 patients before PTCA and absent thereafter.19 20 This means that the FFRmyo values in those patients before and after PTCA represent the “abnormal” and “normal” range of FFRmyo, ie, values whether associated with inducible ischemia or not (Fig 4⇓). In the remaining 2 patients, the ET after 5 to 7 days was still positive, and coronary arteriography was subsequently repeated. In both, the angiographic result was still satisfactory, and FFRmyo, which had been 0.94 and 0.76 at the end of the initial PTCA procedure, was 0.84 and 0.82 at the repeat angiography. In both patients, thallium scintigraphy and stress echocardiography were performed soon thereafter and were normal. Therefore, it is likely that the positive regular ET in these 2 patients was false-positive. For that reason, the pre-PTCA values of FFRmyo in these 2 patients cannot be claimed to be associated with inducible ischemia, which is indicated in Fig 4⇓ by hatching of these 2 points.
In the 5 patients with normal coronary angiograms, FFRmyo was determined in a total of 18 coronary arteries. In all of these vessels, the distal third of the artery could be reached without problems.
The hemodynamic data during catheterization and PTCA are summarized in Table 1⇓. In all patients, steady-state hyperemia was achieved within 2 minutes after the adenosine infusion was begun. In a few patients, some prolongation of the PR interval occurred, but no second-degree AV block was observed. In the majority of the PTCA patients and in all patients with normal angiograms, the adenosine infusion was accompanied by some chest pain or a burning sensation in the neck. During infusion, some decrease of Pa and increase of heart rate were observed compared with baseline, as shown in Table 1⇓.
The maximum hyperemic transstenotic gradients before and after PTCA are presented in Fig 5⇓. The highest hyperemic gradient after successful PTCA was 24 mm Hg. The lowest hyperemic gradient before PTCA and associated with inducible ischemia was 19 mm Hg. This indicates that the gradient itself, when measured at maximum hyperemia with an adequately thin wire, is also a useful parameter, especially if blood pressure is normal.
The values of FFRmyo corresponding to the 18 coronary arteries of the normal subjects are presented in Table 2⇓. All values were close to 1.0, demonstrating that no significant decline of pressure occurred along a normal large epicardial coronary artery.
In all PTCA patients, FFRmyo before PTCA was ≤0.74. After successful PTCA (as assessed by the reversal of a positive ET result), FFRmyo was always >0.74 (Fig 4⇑). Therefore, it can be stated that well-defined ranges of FFRmyo, associated with inducible ischemia or not, can be distinguished with minimal overlap. As a result, the accuracy of FFRmyo to indicate or exclude inducible ischemia (ie, to indicate or exclude a functionally significant coronary stenosis) was close to 100% in this study population. As expected, the spread of FFRmyo before PTCA was significantly larger than after PTCA (P<.01, Wilcoxon’s test for paired observations).
FFRcor and Fractional Collateral Flow
To assess the relative contribution of arterial and collateral flows to myocardial blood flow, Pw must be known.12 Therefore, the separate contributions of collateral and coronary flow to myocardial flow were obtained in those 53 patients in whom Pw was measured. The results for the patient shown in Fig 2⇑ are presented in Table 3⇓, and Table 4⇓ summarizes the results for all 53 patients.
The pressure-derived fractional collateral blood flow was 15±8% (range, 2% to 35%) before and 4±3% (range, 0% to 12%) after PTCA. From the differences in FFRmyo and FFRcor in these tables, it can be understood that if the contribution of collateral flow to myocardial flow is not known, coronary flow indexes overestimate the physiological impact of the stenosis.
Rationale of FFR
At present, there is little doubt that evaluation of the significance of a coronary stenosis only by quantifying its luminal narrowing on the angiogram is a fundamentally flawed approach.5 Therefore, the importance of endeavors to obtain information about flow is indisputable. Early investigators tried to measure absolute flow, expressed in milliliters per minute.21 22 Absolute flow, however, varies widely between different persons and between different coronary arteries. Therefore, expressing flow as an absolute volume is meaningless when the extent of the myocardial distribution supplied by the artery is unknown. For this reason, other ways to express flow have been searched for, resulting in the concept of (absolute) CFR by Gould et al in 1974,23 defined as the ratio of hyperemic to resting flow in a coronary artery. This concept has stimulated interest in and understanding of coronary blood flow regulation in an unparalleled way. In clinical practice, however, the dependency of absolute CFR on hemodynamic loading conditions, heart rate, and some other confounding factors has hampered its use, and normal values show a considerable interstudy variability.6 7 8 24 25 26
Relative CFR, defined as hyperemic flow in the stenotic artery divided by hyperemic flow in a normal reference artery,7 is independent of pressure changes but is applicable only if a normal reference artery is available. Both absolute and relative CFRs do not take into account collateral blood flow, which may contribute considerably to myocardial perfusion and modify the functional significance of the coronary stenosis with respect to myocardial (hypo)perfusion.10 11
Therefore, we introduced the concept of FFR as the maximum achievable blood flow in the presence of a stenosis divided by maximum flow in that same distribution as it would be if the supplying artery were normal.12 13 As shown earlier and confirmed in the present study, FFR can be calculated by pressure measurements in the coronary circulation under maximum vasodilated circumstances. In fact, it represents that very fraction of maximum coronary or myocardial blood flow that is preserved despite the presence of the epicardial stenosis.
Because the functional capacity of patients with angina pectoris is directly related to the maximum achievable blood flow to the myocardium, FFRmyo indicates the functional significance of an epicardial coronary lesion for the patient. Because FFRmyo is independent of driving pressure and reflects both antegrade and collateral flow, it is theoretically expected to have advantages compared with absolute flow, flow velocity, classic CFR, or transstenotic pressure gradient alone. An important limitation, however, is present in the case of small-vessel disease, as will be discussed later.
Although the mathematical derivation of the pressure-flow equations may be somewhat complex,12 the rationale of FFRmyo can be clarified by Fig 6⇓. The independence of FFR from pressure changes is illustrated in Fig 7⇓. Figs 6⇓ and 7⇓ are simplified and are intended only to explain intuitively the concept of FFRmyo. Understanding the equation for FFRcor is more difficult. Its mathematical derivation and experimental validation have been described earlier.12
Normal and Pathological Values of FFRmyo
Theoretically, normal FFR equals 1.0 for any vessel and patient under study. This was confirmed in the five patients with normal coronary arteries (Table 2⇑). No significant decline of pressure was found in these normal branches during maximum vasodilation. This confirms earlier experimental observations in different species that under physiological circumstances, the large epicardial coronary arteries provide little resistance to flow.27 28
Because in healthy subjects no myocardial ischemia is inducible, not even at exhaustive exercise, the value of FFRmyo below which ischemia may be inducible is expected to be <1.0. To find that cutoff value and thus define ranges of values of FFRmyo that are associated or not associated with inducible ischemia, it was necessary to have at our disposal a test that unequivocally discriminates between the presence and absence of inducible ischemia.
To achieve that goal, we selected a particular group of patients with stable angina, single-vessel disease, normal left ventricular function, and a positive ET before PTCA that reversed to negative after angiographically successful PTCA. In such a population, false-negative and false-positive tests are excluded and both the positive predictive value of a positive ET before PTCA and the negative predictive value of a negative ET after PTCA are nearly 100%.19 20 Therefore, in that group of patients, ET could be used as a gold standard to indicate or exclude inducible ischemia and to assess ranges of FFRmyo indicating or excluding significant coronary artery disease. As shown in Fig 4⇑, there was only minimal overlap between “normal” and “pathological” values, and the cutoff point was 0.74.
It should be noted in this context that in most patients, FFRmyo after successful PTCA, although obviously sufficient to prevent inducible ischemia, did not completely return to values encountered in normal coronary arteries (Table 4⇑).
Another interesting point is that in a number of previous studies to determine absolute CFR by videodensitometry or by Doppler velocimetry, the cutoff point between significant and nonsignificant lesions was found at values of ≈70% of the normal reference values for those techniques.29 30 31 32
Finally, in Equation 2, no major mistakes are made by omitting Pv, as long as this parameter is not elevated. Therefore, if no conditions are present that are associated with elevated Pv, calculation of FFRmyo is even simpler and approximately equal to hyperemic Pd/Pa.13
Induction of Maximum Arteriolar Vasodilation by Intravenous Adenosine
Because we measured Pa by the guiding catheter, it was undesirable to perform intracoronary injections of a vasodilator because then the Pa signal would have to be interrupted. Therefore, we used intravenous infusion of adenosine at an infusion rate of 140 μg·kg−1·min−1, which is safe, induces steady-state maximum hyperemia within 2 minutes,16 30 and enabled excellent simultaneous recording of Pa, Pd, and Pv in all patients in this study. A disadvantage of systemic administration of adenosine is the possible induction of myocardial steal for cases of severe stenosis and a collateral-dependent myocardium. However, because the systemic effects of intravenous adenosine were limited, as shown in Table 1⇑, we believe that myocardial steal has not been an important confounder in this study.
No adverse reactions were observed during adenosine infusion except some chest discomfort due to its physiological action.
A last qualification in this context is that the reaction of a diseased coronary artery after pharmacological vasodilation can be different from exercise-induced stress. In the latter case, arteriolar vasodilation can be accompanied by paradoxical constriction at the site of the stenosis, provoked by sympathetic nerve stimulation.36 Whatever the role of such a mechanism may be, in most patients exercise-induced ST depression before PTCA was associated with FFRmyo ≤0.74 and absence of ST depression after PTCA with FFRmyo >0.74 in this selected study population. In less uniformly defined patients, applicability of the FFR measurements for indicating physiological stenosis severity may be more limited if exercise-induced paradoxical vasospasm is present.
Transstenotic Pressure Recording by Wires and Comparison With Other Techniques
During past years, several ultrathin guide wires have been developed to reliably measure distal coronary pressure.12 14 15 37 As shown by De Bruyne et al,37 even in the presence of a 90% area stenosis in a 3.0-mm-diameter vessel, the overestimation of translesional pressure gradient by these wires is negligible. In former studies, an open 0.015-in pressure-monitoring guide wire was used to monitor distal coronary pressure.12 13 Frequent flushing of that wire was mandatory, and only a mean pressure signal could be obtained.
Recently, an 0.018-in fiber-optic wire has become available that allows excellent high-fidelity phasic pressure recordings throughout the procedure.14 15 17 38 The distal 30 cm of this wire is comparable to a regular guide wire, and the fiber-optic sensor is located 3 cm from the flexible radiopaque tip (Fig 1⇑). The wire is connected to a small interface and, before use, is zeroed and calibrated outside the patient’s body, which takes 2 minutes. Drift during the procedure is minimal. The steering and torque control of this wire, however, are not as good as in regular guide wires. For that reason, use of a regular guide wire to reach and cross the stenosis was necessary in 19 patients in this study, after which the regular wire was exchanged through the balloon catheter for the fiber-optic wire. If this fiber-optic wire is used in diagnostic studies, especially if the vessels are tortuous or if FFRmyo should be measured in multiple branches, it can be used in connection with a 3F multifunctional probing catheter (Schneider AG), which should be pulled back before translesional pressure is measured. In this way, measurements can be performed safely and rapidly. By use of the fiber-optic wire for continuous intracoronary pressure recording throughout the procedure, not only can FFR be calculated, but also the phasic intracoronary pressure curve can be continuously studied. This allows early recognition of methodological mistakes and provides instantaneous feedback during intracoronary manipulations, contrast injections, etc.
During the past few years, some other intracoronary techniques for assessment of flow reserve have been introduced, of which Doppler velocimetry by a 0.014-in wire (Flowire, Cardiometrics) is the most important. This is an easy and safe technique, and valuable results have been obtained.38 39 40 However, velocity-based CFR is dependent on loading conditions, and normal values of flow velocity and velocity-based CFR show considerable variations.26 31 32 Moreover, obtaining good signals is sometimes difficult in ostial lesions and close to bifurcations because of inhomogeneous velocity patterns at those sites.41 On the other hand, if there is small-vessel disease or diffuse disease distal to the tip of the pressure wire, this will be missed by intracoronary pressure recordings and can be better detected by study of flow velocity.42 43 If the epicardial artery and the distal microvasculature are considered to be two serial components of the coronary circulation, diminished hyperemic flow velocity indicates that somewhere in that system, an obstruction to flow is present: epicardial, microvascular, or both. Subsequently, the decline of hyperemic epicardial coronary pressure, expressed by FFRmyo, is an indication of the extent to which that obstruction is caused by the epicardial lesion. Therefore, in diagnostic studies, pressure-derived FFRmyo and Doppler velocimetry are complementary by providing information on the extent to which the epicardial stenosis and the microvascular disease, if present, each contribute to inducible myocardial ischemia.42 43
Safety of Intracoronary Physiological Measurements by Wire Technology
To obtain FFRmyo, no occlusive intracoronary pressure is needed. The manipulations required are the introduction of a sensor-tipped floppy wire across the stenosis and the administration of a maximum vasodilatory stimulus. In our opinion, it is accepted that introduction of such a wire and comparable devices can be safely performed by experienced operators14 15 16 17 26 32 37 38 39 40 43 44 and that the very small risk is counterbalanced by the valuable information obtained in case of ambiguity about the functional significance of stenosis. In our experience of almost 300 cases, we have never observed complications due to the introduction of this pressure wire into the coronary artery. Obviously, critical long-term follow-up of patients who undergo these measurements remains important.
A special issue in this particular study was the introduction of the wire into normal coronary arteries in the patients of group B to test the hypothesis that normal FFR equals 1.0. This hypothesis has been speculated on and disputed many times. It is germane because one of the special features claimed by the FFR concept is its unequivocal normal value, irrespective of the person or artery under study. Considering the safety of this type of wire in patients with coronary artery disease and taking into account that in previous studies it has also been considered acceptable to perform physiological measurements in a limited number of normal coronary arteries by wire or 2F to 3F catheter technology,26 32 33 36 45 we believe that the importance of our objective was in proportion to the inconvenience and minimal risk for the participants (in accordance with the Helsinki declaration).
The clinical implications of this study may be important. In diagnostic catheterization, the significance of an epicardial coronary lesion in terms of inducibility of ischemia can be better assessed. Especially in patients with an intermediate stenosis in one of the large epicardial coronary arteries, this technique can be helpful in deciding on revascularization if ambiguity exists with respect to the functional significance of that stenosis.
Because this study was restricted to patients with single-vessel disease, further studies are warranted before the results can be applied in multivessel disease and a number of other conditions discussed below.
In interventional cardiology, great concern exists about the large number of patients undergoing PTCA without prior objective evidence of ischemia at ET, thallium scintigraphy, or other tests.46 Since the prevalence of coronary artery stenosis in an arbitrary population of asymptomatic 60-year-old men is 20%,47 it is not unlikely that in a number of patients with negative noninvasive tests but accepted for PTCA on anatomic grounds, the coronary lesion found at angiography is coincidental and the PTCA is performed unnecessarily. If FFRmyo is measured before PTCA, some of these cases can be better identified and unnecessary PTCAs may be avoided.
At present, this approach of calculating FFR by pressure measurements has some important limitations. The most fundamental limitation is small-vessel disease distal to the location at which Pd is measured. The theoretical and experimental model on which the equations for FFRmyo and FFRcor are based assumes a normal microcirculation.12 In case of small-vessel disease, FFR represents maximum flow in the presence of an epicardial stenosis, expressed as a fraction of maximum flow in the absence of the epicardial stenosis but still not normal because of the presence of the distal small-vessel disease. This can be the case in, eg, diabetes but also may play a role after myocardial infarction or successful thrombolysis. Likewise, in diffuse coronary atherosclerosis, FFRmyo fails to measure the effects of the diffuse disease beyond the tip of the pressure-measuring device.
Also, in cases of left ventricular hypertrophy, poor response to coronary vasodilators, and other conditions in which the cause of decreased maximum flow is located distal to the epicardial coronary artery, the value of FFRmyo to detect that disease is limited. In those cases, this approach allows only detection of the extent to which the epicardial stenosis contributes to the myocardial flow impairment. Although in those cases FFRmyo may help to decide whether a PTCA of the epicardial stenosis will help to reduce ischemia, the severity of myocardial flow impairment is underestimated because distal or microvascular disease is not accounted for. To assess both epicardial and small-vessel disease, simultaneous measurement of hyperemic intracoronary pressure and blood flow velocity is mandatory, as discussed before.42 43 Furthermore, the cutoff point of FFRmyo of 0.74 was arrived at in a very specific population of patients with single-vessel disease and normal left ventricular function, and therefore it cannot be applied in other groups of patients without further validation studies. As has been clarified, the confinement to such a specific population was necessary to dispose of a gold standard of ischemia.
Finally, some technical characteristics of the fiber-optic wire in terms of steerability and pushability should be improved, and for the time being, we recommend that its use for diagnostic studies be restricted to interventional laboratories.
FFRmyo is a lesion-specific index that reflects the effect of the epicardial stenosis on maximum myocardial perfusion. In this study, it was confirmed that normal FFRmyo equals 1.0 and that no decline of pressure occurs along normal epicardial coronary arteries. Moreover, in patients with single-vessel disease and normal left ventricular function, a value of FFRmyo of 0.74 discriminated between lesions associated with inducible ischemia and those not. Therefore, FFRmyo is a useful index to assess the functional significance of an epicardial coronary artery stenosis with potential application in both diagnostic and interventional procedures.
Selected Abbreviations and Acronyms
|CFR||=||coronary flow reserve|
|FFR||=||fractional flow reserve|
|Pa||=||mean arterial pressure|
|Pd||=||mean distal coronary (transstenotic) pressure|
|PTCA||=||percutaneous transluminal coronary angioplasty|
|Pv||=||mean central venous pressure|
|Pw||=||mean coronary wedge pressure|
The authors gratefully acknowledge the assistance of the staff of the cardiac catheterization laboratory; of Guy van Dael, medical photographer; and of Bert Jan Arends, PhD, for the statistical analysis. The unequaled help of Anne Hol in preparing the manuscript is particularly appreciated.
Presented in part at the 67th Scientific Sessions of the American Heart Association, Dallas, Tex, November 14-17, 1994.
- Received November 29, 1994.
- Revision received June 27, 1995.
- Accepted July 7, 1995.
- Copyright © 1995 by American Heart Association
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