(Circulation. 1995;92:3183-3193.)
© 1995 American Heart Association, Inc.
Articles |
Fractional Flow Reserve
A Useful Index to Evaluate the Influence of an Epicardial Coronary Stenosis on Myocardial Blood Flow
Presented in part at the 67th Scientific Sessions of the American Heart Association, Dallas, Tex, November 14-17, 1994.
From the Department of Cardiology, Catharina Hospital, Eindhoven, Netherlands.
Correspondence to Nico H.J. Pijls, MD, PhD, Department of Cardiology, Catharina Hospital, PO Box 1350, 5602 ZA Eindhoven, Netherlands.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion References |
|---|
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.
Key Words: fractional flow reserve • collateral circulation • blood flow
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
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.
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Study Design
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
 | (1) |
and
 | (2) |
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.
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
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.
Hemodynamic Data
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.
|
Pmax) before and after PTCA. For further
explanation see Fig 4
FFRmyo
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.
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
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
The vasoactive drugs used to achieve maximum
coronary
vasodilation have been thoroughly studied by various
investigators.16 30 33 34 35
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).
Clinical Implications
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.
Limitations
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.
Conclusions
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 |
|---|
|
|
Acknowledgments |
|---|
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.
Received November 29, 1994; revision received June 27, 1995; accepted July 7, 1995.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. White CW, Wright CB, Doty DB, Hiratza LF, Eastham CL, Harrison DG, Marcus ML. Does visual interpretation of the coronary arteriogram predict the physiological importance of a coronary stenosis? N Engl J Med. 1984;310:819-824. [Abstract]
2. Klocke FJ. Cognition in the era of technology: `seeing the shades of gray.' J Am Coll Cardiol. 1990;16:763-769. [Medline] [Order article via Infotrieve]
3.
Marcus ML, White CW, Wilson RF. Methods of
measurement of myocardial blood flow in patients: a critical
review. Circulation. 1987;76:245-252.
4.
Hoffmann JIE. Maximal coronary flow and
the concept of coronary vascular reserve.
Circulation. 1984;70:153-159.
5.
Nissen SE, Gurley JC. Assessment of the
functional significance of coronary stenosis: is
digital angiography the answer?
Circulation. 1990;81:1431-1435.
6. Kirkeeide RL, Gould KL, Parsel L. Assessment of coronary stenoses by myocardial perfusion during pharmacologic coronary vasodilation, VIII: validation of coronary flow reserve as a single integrated functional measure of stenosis severity reflecting all its geometric dimensions. J Am Coll Cardiol. 1986;7:103-113. [Abstract]
7. Gould KL, Kirkeeide RL, Buchi M. Coronary flow reserve as a physiologic measure of stenosis severity. J Am Coll Cardiol. 1990;15:459-474. [Abstract]
8. Hongo M, Nakatsuka T, Watanabe N, Takenaka H, Tanaka M, Kinoshita O, Okubo S, Sekiguchi M. Effects of heart rate on phasic coronary blood flow pattern and flow reserve in patients with normal coronary arteries: a study with an intravascular Doppler catheter and spectral analysis. Am Heart J. 1994;127:545-551. [Medline] [Order article via Infotrieve]
9.
Uren NG, Melin JA, De Bruyne B, Wijns W, Baudhuin T,
Camici PG. Relation between myocardial blood flow and the
severity of coronary artery stenosis.
N Engl J Med. 1994;330:1782-1788.
10. Pijls NHJ, Bech GJW, El Gamal MIH, Bonnier JJRM, De Bruyne B, Van Gelder B, Michels HR, Koolen JJ. Quantification of recruitable coronary collateral blood flow in conscious man and its potential to predict future ischemic events. J Am Coll Cardiol. 1995;25:1522-1528. [Abstract]
11.
Vanoverschelde JLJ, Wijns W, Depré C, Essamri B,
Heyndrickx GR, Borgers M, Bol A, Melin JA. Mechanisms of chronic
regional postischemic dysfunction in humans: new insights
from the study of noninfarcted collateral-dependent
myocardium. Circulation. 1993;87:1513-1523.
12.
Pijls NHJ, Van Son JAM, Kirkeeide RL, De Bruyne B,
Gould KL. Experimental basis of determining maximum
coronary, myocardial, and collateral blood flow by pressure
measurements for assessing functional stenosis severity before
and after percutaneous transluminal coronary
angioplasty. Circulation. 1993;87:1354-1367.
13.
De Bruyne B, Baudhuin T, Melin JA, Pijls NHJ, Sys SU,
Bol A, Paulus WJ, Heyndrickx GR, Wijns W. Coronary flow
reserve calculated from pressure measurements in humans: validation
with positron emission tomography.
Circulation. 1994;89:1013-1022.
14. Emanuelsson H, Dohnal M, Lamm C, Tenerz L. Initial experiences with a miniaturized pressure transducer during coronary angioplasty. Cathet Cardiovasc Diagn. 1991;24:137-143. [Medline] [Order article via Infotrieve]
15. Lamm C, Dohnal M, Serruys PW, Emanuelsson H. High fidelity translesional pressure gradients during percutaneous transluminal coronary angioplasty: correlation with quantitative coronary angiography. Am Heart J. 1993;126:66-75. [Medline] [Order article via Infotrieve]
16.
Wilson RF, Wyche K, Christensen BV, Zimmer S, Laxson
DD. Effects of adenosine on human coronary
arterial circulation.
Circulation. 1990;82:1595-1606.
17. Pijls NHJ, De Bruyne B. Practice and interpretation of intracoronary pressure recordings and calculation of flow reserve. In: Bertrand M, Serruys PW, Sigwart U, eds. Handbook of Interventional Cardiology. London, UK: Churchill Livingstone; 1995. In press.
18.
Reiber JHC, Serruys PW, Kooyman CJ, Wijns W, Slager CJ,
Gerbrands JJ, Schuurbiers JCH, Den Boer A, Hugenholtz PG.
Assessment of short-, medium-, and long-term variations in
arterial dimensions from computer-assisted
quantification of coronary cineangiograms.
Circulation. 1985;71:280-288.
19. Hamilton GW, Trobaugh GB, Ritchie JL, Gould KL, DeRouen A, Williams DL. Myocardial imaging with 201thallium: an analysis of clinical usefulness based on Bayes' theorem. Semin Nucl Med. 1978;8:358-364.[Medline] [Order article via Infotrieve]
20.
Melin JA, Piret LJ, Vanbutsele RJM, Rousseau MF, Cosyns
J, Brasseur LA, Beckers C, Detry JMR. Diagnostic
value of exercise electrocardiography and
thallium myocardial scintigraphy in patients without
previous myocardial infarction: a bayesian approach.
Circulation. 1981;63:1019-1024.
21. Rutishauser W, Noseda G, Bussman WD, Preter B. Blood flow measurement through single coronary arteries by roentgen densitometry, II: right coronary artery flow in conscious man. Am J Roentgenol. 1970;109:21-24. [Abstract]
22.
Ganz W, Donoso R, Tamura K, Marcus HS, Yoshiola S, Swan
HJC. Measurement of coronary sinus blood flow by
continuous thermodilation in man.
Circulation. 1971;44:181-195.
23. Gould KL, Lipscomb K, Hamilton GW. Physiologic basis for assessing critical coronary stenosis: instantaneous flow response and regional distribution during coronary hyperemia as measures of coronary flow reserve. Am J Cardiol. 1974;33:87-94. [Medline] [Order article via Infotrieve]
24.
Hess OM, McGillem MJ, De Boe SF, Pinto IMF, Gallagher
KP, Mancini GBJ. Determination of coronary flow reserve
by parametric imaging.
Circulation. 1990;82:1438-1448.
25. Gould KL. Functional measures of coronary stenosis severity at cardiac catheterization. J Am Coll Cardiol. 1990;16:198-199. [Medline] [Order article via Infotrieve]
26. Ofili EO, Labovitz J, Kern MJ. Coronary flow velocity dynamics in normal and diseased arteries. Am J Cardiol. 1993;71:3D-9D. [Medline] [Order article via Infotrieve]
27. Folts JD, Gallagher K, Rowe GG. Hemodynamic effects of controlled degrees of coronary artery stenosis in short-term and long-term studies in dogs. J Thorac Cardiovasc Surg.. 1977;73:722-727. [Abstract]
28.
Young DF, Cholvin NR, Roth AC. Flow in the major
branches of the left coronary artery during experimental
coronary insufficiency in the unanesthetized
dog. Circ Res. 1975;36:735-743.
29. Zijlstra F, Reiber JHC, Juillière Y, Serruys PW. Normalization of coronary flow reserve by percutaneous transluminal coronary angioplasty. Am J Cardiol. 1988;61:55-63. [Medline] [Order article via Infotrieve]
30. Kern MJ, Deligonul U, Tatineni S, Serota H, Aguirre FV, Hilton TC. Intravenous adenosine continuous infusion and low dose bolus administration for determination of coronary vasodilatory reserve in patients with and without coronary artery disease. J Am Coll Cardiol. 1991;18:718-729. [Abstract]
31. Wilson RF. Assessment of the human coronary circulation using a Doppler catheter. Am J Cardiol. 1991;67:44D-56D. [Medline] [Order article via Infotrieve]
32.
McGinn AL, White CW, Wilson RF. Interstudy
variability of coronary flow reserve: influence of heart rate,
arterial pressure, and ventricular
preload. Circulation. 1990;81:1319-1330.
33.
Wilson RF, White CW. Intracoronary
papaverine: an ideal coronary vasodilator for studies of the
coronary circulation in conscious humans.
Circulation. 1986;73:444-451.
34. Zijlstra F, Juillière Y, Serruys PW, Roelandt JRTC. Value and limitations of intracoronary adenosine for the assessment of coronary flow reserve. Cathet Cardiovasc Diagn. 1988;15:76-80. [Medline] [Order article via Infotrieve]
35. Wilson RF, White CW. Serious ventricular dysrhythmias after intracoronary papaverine. Am J Cardiol. 1988;62:1301-1302. [Medline] [Order article via Infotrieve]
36.
Nabel EG, Ganz JB, Alexander RW, Selwyn AP.
Dilation of normal and constriction of atherosclerotic coronary
arteries caused by the cold pressor test.
Circulation. 1988;77:43-52.
37. De Bruyne B, Pijls NHJ, Paulus WJ, VanTrimpont PJ, Sys SU, Heyndrickx GR. Transstenotic coronary pressure gradient measurement in humans: in vitro and in vivo evaluation of a new pressure monitoring guide wire. J Am Coll Cardiol. 1993;22:119-126. [Abstract]
38. Serruys PW, Di Mario C, Meneveau N, De Jaegere P, Strikwerda S, De Feyter PJ, Emanuelsson H. Intracoronary pressure and flow velocity with sensor-tip guide wires: a new methodologic approach for assessment of coronary hemodynamics before and after coronary interventions. Am J Cardiol. 1993;71:41D-53D. [Medline] [Order article via Infotrieve]
39. Kern MJ, Donohue TJ, Aguirre FV, Bach RG, Caraccido EA, Ofili E, Labovitz AJ. Assessment of angiographically intermediate coronary artery stenosis using the Doppler Flowire. Am J Cardiol. 1993;71:26D-33D. [Medline] [Order article via Infotrieve]
40. Anderson HV, Kirkeeide RL, Stuart Y, Smaling RW, Heibig J, Willerson JT. Coronary artery flow monitoring following coronary interventions. Am J Cardiol. 1993;71:62D-69D. [Medline] [Order article via Infotrieve]
41. Kern MJ, Donohue TJ, Flynn MS, Aguirre FV, Bach RG, Caracciolo EA. Limitations of translesional pressure and flow velocity for long ostial left anterior descending stenoses. Cathet Cardiovasc Diagn. 1994;33:50-54. [Medline] [Order article via Infotrieve]
42.
Mancini GBJ, McGillem MJ, De Boe SF, Gallagher
KP. The diastolic hyperemic flow versus
pressure slope index: microsphere validation of an alternative
to measures of coronary reserve.
Circulation. 1991;84:862-870.
43. Di Mario C, Krams R, Gil R, Meneveau N, Serruys PW. The instantaneous hyperemic pressure-flow relationship in conscious humans. In: Reiber JHC, Serruys PW, eds. Progress in Quantitative Coronary Arteriography. Dordrecht, Netherlands: Kluwer Academic Publishers; 1994:247-268.
44. Di Mario C, Meneveau N, Gil R, De Jaegere P, De Feyter PJ, Slager CJ, Roelandt JRTC, Serruys PW. Maximal blood flow velocity in severe coronary stenoses measured with a Doppler guidewire. Am J Cardiol. 1993;71:54D-61D. [Medline] [Order article via Infotrieve]
45.
Nissen SE, Gurley JC, Grines CL, Booth DC, McClure R,
Berk M, Fischer C, De Maria AN. Intravascular ultrasound
assessment of lumen size and wall morphology in normal subjects and
patients with coronary artery disease.
Circulation. 1991;84:1087-1099.
46.
Topol EJ, Ellis SG, Cosgrove DM, Bates ER, Muller DWM,
Schork NJ, Schork MA, Loop FD. Analysis of
coronary angioplasty practice in the United States with an
insurance-claims data base.
Circulation. 1993;87:1489-1497.
47.
Chaitman BR, Bourassa MG, Davis K, Rogers WJ, Tyras DH,
Berger R, Kennedy JW, Fisher L, Judkins MP, Mock MB, Killip T.
Angiographic prevalence of high-risk coronary artery
disease in patient subsets. Circulation. 1981;64:360-367.
This article has been cited by other articles:
 |
|
 |
|
  F. H. Messerli and G. S. Panjrath The J-curve between blood pressure and coronary artery disease or essential hypertension: exactly how essential? J. Am. Coll. Cardiol., November 10, 2009; 54(20): 1827 - 1834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Hajjiri, M. B. Leavitt, H. Zheng, A. E. Spooner, A. J. Fischman, and H. Gewirtz Comparison of Positron Emission Tomography Measurement of Adenosine-Stimulated Absolute Myocardial Blood Flow Versus Relative Myocardial Tracer Content for Physiological Assessment of Coronary Artery Stenosis Severity and Location J. Am. Coll. Cardiol. Img., June 1, 2009; 2(6): 751 - 758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Sarno, I. Decraemer, P. K. Vanhoenacker, B. De Bruyne, M. Hamilos, T. Cuisset, E. Wyffels, J. Bartunek, G. R. Heyndrickx, and W. Wijns On the Inappropriateness of Noninvasive Multidetector Computed Tomography Coronary Angiography to Trigger Coronary Revascularization: A Comparison With Invasive Angiography J. Am. Coll. Cardiol. Intv., June 1, 2009; 2(6): 550 - 557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Samady, M. McDaniel, E. Veledar, B. De Bruyne, N. H. Pijls, W. F. Fearon, and V. Vaccarino Baseline Fractional Flow Reserve and Stent Diameter Predict Optimal Post-Stent Fractional Flow Reserve and Major Adverse Cardiac Events After Bare-Metal Stent Deployment J. Am. Coll. Cardiol. Intv., April 1, 2009; 2(4): 357 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kawamura, H. Nakajima, and J. Kobayashi Reply to Maros Eur. J. Cardiothorac. Surg., March 1, 2009; 35(3): 556 - 557. [Full Text] [PDF]
|
|
|
|
 |
|
 P. A.L. Tonino, B. De Bruyne, N. H.J. Pijls, U. Siebert, F. Ikeno, M. van `t Veer, V. Klauss, G. Manoharan, T. Engstrom, K. G. Oldroyd, et al. Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention N. Engl. J. Med., January 15, 2009; 360(3): 213 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Di Mario, G. R. Heyndrickx, F. Prati, and N. H.J. Pijls CHAPTER 8 Invasive Imaging and Haemodynamics ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. H. Jung, J. Rieber, S. Stork, C. Hoyer, I. Erhardt, A. Nowotny, W. Voelker, F. Weidemann, G. Ertl, V. Klauss, et al. Effect of contrast application on interpretability and diagnostic value of dobutamine stress echocardiography in patients with intermediate coronary lesions: comparison with myocardial fractional flow reserve Eur. Heart J., October 2, 2008; 29(20): 2536 - 2543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. B. Meijboom, C. A.G. Van Mieghem, N. van Pelt, A. Weustink, F. Pugliese, N. R. Mollet, E. Boersma, E. Regar, R. J. van Geuns, P. J. de Jaegere, et al. Comprehensive Assessment of Coronary Artery Stenoses: Computed Tomography Coronary Angiography Versus Conventional Coronary Angiography and Correlation With Fractional Flow Reserve in Patients With Stable Angina J. Am. Coll. Cardiol., August 19, 2008; 52(8): 636 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B De Bruyne and J Sarma Fractional flow reserve: a review Heart, July 1, 2008; 94(7): 949 - 959. [Full Text] [PDF]
|
|
|
|
|
|
W. Aarnoudse, M. van't Veer, N. H.J. Pijls, J. ter Woorst, S. Vercauteren, P. Tonino, M. Geven, M. Rutten, E. van Hagen, B. de Bruyne, et al. Direct Volumetric Blood Flow Measurement in Coronary Arteries by Thermodilution J. Am. Coll. Cardiol., December 11, 2007; 50(24): 2294 - 2304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. O. Jensen, P. Thayssen, L. Thuesen, H. S. Hansen, J. F. Lassen, H. Kelbaek, A. Junker, K. N. Hansen, H. E. Boetker, L. R. Krusell, et al. Influence of a Pressure Gradient Distal to Implanted Bare-Metal Stent on In-Stent Restenosis After Percutaneous Coronary Intervention Circulation, December 11, 2007; 116(24): 2802 - 2808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Marques, P. Knaapen, R. Boellaard, A. A. Lammertsma, N. Westerhof, and F. C. Visser Microvascular Function in Viable Myocardium After Chronic Infarction Does Not Influence Fractional Flow Reserve Measurements J. Nucl. Med., December 1, 2007; 48(12): 1987 - 1992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. di Mario and K. Dimopoulos The Effect of Drug-Eluting Stents on Collateral Coronary Flow J. Am. Coll. Cardiol., August 7, 2007; 50(6): 560 - 560. [Full Text] [PDF]
|
|
|
|
|
|
M. A. Costa, S. Shoemaker, H. Futamatsu, C. Klassen, D. J. Angiolillo, M. Nguyen, A. Siuciak, P. Gilmore, M. M. Zenni, L. Guzman, et al. Quantitative Magnetic Resonance Perfusion Imaging Detects Anatomic and Physiologic Coronary Artery Disease as Measured by Coronary Angiography and Fractional Flow Reserve J. Am. Coll. Cardiol., August 7, 2007; 50(6): 514 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Weidemann, P. Jung, C. Hoyer, J. Broscheit, W. Voelker, G. Ertl, S. Stork, C. E. Angermann, and J. M. Strotmann Assessment of the contractile reserve in patients with intermediate coronary lesions: a strain rate imaging study validated by invasive myocardial fractional flow reserve Eur. Heart J., June 2, 2007; 28(12): 1425 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Botman, J. Schonberger, S. Koolen, O. Penn, H. Botman, N. Dib, E. Eeckhout, and N. Pijls Does Stenosis Severity of Native Vessels Influence Bypass Graft Patency? A Prospective Fractional Flow Reserve-Guided Study Ann. Thorac. Surg., June 1, 2007; 83(6): 2093 - 2097. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Verberne, M. Meuwissen, S. A. J. Chamuleau, B.-J. Verhoeff, B. L. F. van Eck-Smit, J. A. E. Spaan, J. J. Piek, and M. Siebes Effect of simultaneous intracoronary guidewires on the predictive accuracy of functional parameters of coronary lesion severity Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2349 - H2355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Botman, H. Post, O. Penn, and N. Pijls Value of Magnetic Resonance Imaging, Angiography, and Fractional Flow Reserve to Evaluate the Left Main Coronary Artery After Direct Surgical Angioplasty Ann. Thorac. Surg., February 1, 2007; 83(2): 490 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. J. Marques, M. J. van Eenige, H. J. Spruijt, N. Westerhof, J. Twisk, C. A. Visser, and F. C. Visser The diastolic flow velocity-pressure gradient relation and dpv50 to assess the hemodynamic significance of coronary stenoses Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2630 - H2635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Werner, R. Surber, M. Ferrari, M. Fritzenwanger, and H. R. Figulla The functional reserve of collaterals supplying long-term chronic total coronary occlusions in patients without prior myocardial infarction Eur. Heart J., October 2, 2006; 27(20): 2406 - 2412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Kern, A. Lerman, J.-W. Bech, B. De Bruyne, E. Eeckhout, W. F. Fearon, S. T. Higano, M. J. Lim, M. Meuwissen, J. J. Piek, et al. Physiological Assessment of Coronary Artery Disease in the Cardiac Catheterization Laboratory: A Scientific Statement From the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology Circulation, September 19, 2006; 114(12): 1321 - 1341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Werner, M. Fritzenwanger, D. Prochnau, G. Schwarz, M. Ferrari, W. Aarnoudse, N. H.J. Pijls, and H. R. Figulla Determinants of Coronary Steal in Chronic Total Coronary Occlusions: Donor Artery, Collateral, and Microvascular Resistance J. Am. Coll. Cardiol., July 4, 2006; 48(1): 51 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zimarino, A. Ausiello, G. Contegiacomo, I. Riccardi, G. Renda, C. Di Iorio, and R. De Caterina Rapid Decline of Collateral Circulation Increases Susceptibility to Myocardial Ischemia: The Trade-Off of Successful Percutaneous Recanalization of Chronic Total Occlusions J. Am. Coll. Cardiol., July 4, 2006; 48(1): 59 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rieber, A. Huber, I. Erhard, S. Mueller, M. Schweyer, A. Koenig, T. M. Schiele, K. Theisen, U. Siebert, S. O. Schoenberg, et al. Cardiac magnetic resonance perfusion imaging for the functional assessment of coronary artery disease: a comparison with coronary angiography and fractional flow reserve Eur. Heart J., June 2, 2006; 27(12): 1465 - 1471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Botman, W. Arnoudse, O. Penn, and N. Pijls Long-Term Outcome After Surgical Left Main Coronary Angioplasty Ann. Thorac. Surg., March 1, 2006; 81(3): 828 - 834. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Legalery, F. Schiele, M.-F. Seronde, N. Meneveau, H. Wei, K. Didier, M.-C. Blonde, F. Caulfield, and J.-P. Bassand One-year outcome of patients submitted to routine fractional flow reserve assessment to determine the need for angioplasty Eur. Heart J., December 2, 2005; 26(24): 2623 - 2629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. G. E. VanTeeffelen, S. Dekker, D. S. Fokkema, M. Siebes, H. Vink, and J. A. E. Spaan Hyaluronidase treatment of coronary glycocalyx increases reactive hyperemia but not adenosine hyperemia in dog hearts Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2508 - H2513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kruger, K.-C. Koch, I. Kaumanns, M. W. Merx, P. Hanrath, and R. Hoffmann Clinical Significance of Fractional Flow Reserve for Evaluation of Functional Lesion Severity in Stent Restenosis and Native Coronary Arteries Chest, September 1, 2005; 128(3): 1645 - 1649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. E. Vicario, L. Cirillo, G. Storto, T. Pellegrino, N. Ragone, L. Fontanella, M. Petretta, D. Bonaduce, and A. Cuocolo Influence of Risk Factors on Coronary Flow Reserve in Patients with 1-Vessel Coronary Artery Disease J. Nucl. Med., September 1, 2005; 46(9): 1438 - 1443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Berger, K.-J. Botman, P. A. MacCarthy, W. Wijns, J. Bartunek, G. R. Heyndrickx, N. H.J. Pijls, and B. De Bruyne Long-Term Clinical Outcome After Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease J. Am. Coll. Cardiol., August 2, 2005; 46(3): 438 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-P. Liu, Y.-H. Ling, and H.-L. Kao Use of a Pressure-Sensing Wire to Detect Sequential Pressure Gradients for Ipsilateral Vertebral and Subclavian Artery Stenoses AJNR Am. J. Neuroradiol., August 1, 2005; 26(7): 1810 - 1812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Roy, R. K. Banerjee, L. H. Back, M. R. Back, S. Khoury, and R. W. Millard Delineating the guide-wire flow obstruction effect in assessment of fractional flow reserve and coronary flow reserve measurements Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H392 - H397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lindstaedt, M. K. Fritz, A. Yazar, C. Perrey, A. Germing, P. H. Grewe, A. M. Laczkovics, A. Mugge, and W. Bojara Optimizing revascularization strategies in patients with multivessel coronary disease: Impact of intracoronary pressure measurements J. Thorac. Cardiovasc. Surg., April 1, 2005; 129(4): 897 - 903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V Klauss, P Erdin, J Rieber, M Leibig, H-U Stempfle, A Konig, M Baylacher, K Theisen, M C Haufe, G Sroczynski, et al. Fractional flow reserve for the prediction of cardiac events after coronary stent implantation: results of a multivariate analysis Heart, February 1, 2005; 91(2): 203 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. H J Pijls Optimum guidance of complex PCI by coronary pressure measurement Heart, September 1, 2004; 90(9): 1085 - 1093. [Full Text] [PDF]
|
|
|
|
|
|
W. F. Fearon, W. Aarnoudse, N. H.J. Pijls, B. De Bruyne, L. B. Balsam, D. T. Cooke, R. C. Robbins, P. J. Fitzgerald, A. C. Yeung, and P. G. Yock Microvascular Resistance Is Not Influenced by Epicardial Coronary Artery Stenosis Severity: Experimental Validation Circulation, May 18, 2004; 109(19): 2269 - 2272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. K. Hau Fractional flow reserve and complex coronary pathologic conditions Eur. Heart J., May 1, 2004; 25(9): 723 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Orford, A. Lerman, and D. R. Holmes Routine intravascular ultrasound guidance of percutaneous coronary intervention: A critical reappraisal J. Am. Coll. Cardiol., April 21, 2004; 43(8): 1335 - 1342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R Lopez-Palop, D Saura, E Pinar, I Lozano, F Perez-Lorente, F Pico, and M Valdez Adequate intracoronary adenosine doses to achieve maximum hyperaemia in coronary functional studies by pressure derived fractional flow reserve: a dose response study Heart, January 1, 2004; 90(1): 95 - 96. [Full Text] [PDF]
|
|
|
|
|
|
Y. Takagi, K. Ohmori, K. Yukiiri, I. Kondo, Y. Yu, A. Oshita, H. Takeuchi, K. Mizushige, and M. Kohno Quantitative assessment of coronary stenosis by harmonic power Doppler with a simple pulsing sequence and vasodilator stress in patients J. Am. Coll. Cardiol., June 4, 2003; 41(11): 2060 - 2067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Leesar, T. Abdul-Baki, N. I. Akkus, A. Sharma, T. Kannan, and R. Bolli Use of fractional flow reserve versus stress perfusion scintigraphy after unstable angina: Effect on duration of hospitalization, cost, procedural characteristics, and clinical outcome J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1115 - 1121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. H. J. Pijls Is it time to measure fractional flow reserve in all patients? J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1122 - 1124. [Full Text] [PDF]
|
|
|
|
|
|
D V Cokkinos, A Manginas, and V Voudris Coronary flow: clinical considerations Heart, April 1, 2003; 89(4): 361 - 363. [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. LaDisa Jr., D. A. Hettrick, L. E. Olson, I. Guler, E. R. Gross, T. T. Kress, J. R. Kersten, D. C. Warltier, and P. S. Pagel Stent implantation alters coronary artery hemodynamics and wall shear stress during maximal vasodilation J Appl Physiol, December 1, 2002; 93(6): 1939 - 1946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Siebes, S. A. J. Chamuleau, M. Meuwissen, J. J. Piek, and J. A. E. Spaan Influence of hemodynamic conditions on fractional flow reserve: parametric analysis of underlying model Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1462 - H1470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Werner and H. R. Figulla Direct Assessment of Coronary Steal and Associated Changes of Collateral Hemodynamics in Chronic Total Coronary Occlusions Circulation, July 23, 2002; 106(4): 435 - 440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Meuwissen, M. Siebes, S. A.J. Chamuleau, B. L.F. van Eck-Smit, K. T. Koch, R. J. de Winter, J. G.P. Tijssen, J. A.E. Spaan, and J. J. Piek Hyperemic Stenosis Resistance Index for Evaluation of Functional Coronary Lesion Severity Circulation, July 23, 2002; 106(4): 441 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. J. Marques, H. J. Spruijt, C. Boer, N. Westerhof, C. A. Visser, and F. C. Visser The diastolic flow-pressure gradient relation in coronary stenoses in humans J. Am. Coll. Cardiol., May 15, 2002; 39(10): 1630 - 1636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Brosh, S. T. Higano, M. J. Slepian, H. I. Miller, M. J. Kern, R. J. Lennon, D. R. Holmes Jr, and A. Lerman Pulse transmission coefficient: a novel nonhyperemic parameter for assessing the physiological significance of coronary artery stenoses J. Am. Coll. Cardiol., March 20, 2002; 39(6): 1012 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nishida, C. Di Mario, M.J. Kern, T.J. Anderson, I. Moussa, R. Bonan, T. Muramatsu, A.C. Jain, J. Suarez de Lezo, S.Y. Cho, et al. Impact of final coronary flow velocity reserve on late outcome following stent implantation Eur. Heart J., February 2, 2002; 23(4): 331 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rodes-Cabau, J. Candell-Riera, E. Domingo, J. Castell-Conesa, I. Anivarro, J. Angel, S. Aguade-Bruix, F. Padilla, A. Soto, and J. Soler-Soler Frequency and Clinical Significance of Myocardial Ischemia Detected Early After Coronary Stent Implantation J. Nucl. Med., December 1, 2001; 42(12): 1768 - 1772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. De Bruyne, F. Hersbach, N. H.J. Pijls, J. Bartunek, J.-W. Bech, G. R. Heyndrickx, K. L. Gould, and W. Wijns Abnormal Epicardial Coronary Resistance in Patients With Diffuse Atherosclerosis but "Normal" Coronary Angiography Circulation, November 13, 2001; 104(20): 2401 - 2406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G J W Bech, H Droste, N H J Pijls, B De Bruyne, J J R M Bonnier, H R Michels, K H Peels, and J J Koolen Value of fractional flow reserve in making decisions about bypass surgery for equivocal left main coronary artery disease Heart, November 1, 2001; 86(5): 547 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. F. Fearon, J. Luna, H. Samady, E. R. Powers, T. Feldman, N. Dib, E. M. Tuzcu, M. W. Cleman, T. M. Chou, D. J. Cohen, et al. Fractional Flow Reserve Compared With Intravascular Ultrasound Guidance for Optimizing Stent Deployment Circulation, October 16, 2001; 104(16): 1917 - 1922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. De Bruyne, N. H.J. Pijls, J. Bartunek, K. Kulecki, J.-W. Bech, H. De Winter, P. Van Crombrugge, G. R. Heyndrickx, and W. Wijns Fractional Flow Reserve in Patients With Prior Myocardial Infarction Circulation, July 10, 2001; 104(2): 157 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Kern and B. Meier Evaluation of the Culprit Plaque and the Physiological Significance of Coronary Atherosclerotic Narrowings Circulation, June 26, 2001; 103(25): 3142 - 3149. [Full Text] [PDF]
|
|
|
|
|
|
G. J. W. Bech, B. De Bruyne, N. H.J. Pijls, E. D. de Muinck, J. C.A. Hoorntje, J. Escaned, P. R. Stella, E. Boersma, J. Bartunek, J. J. Koolen, et al. Fractional Flow Reserve to Determine the Appropriateness of Angioplasty in Moderate Coronary Stenosis : A Randomized Trial Circulation, June 19, 2001; 103(24): 2928 - 2934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Smith Jr, J. T. Dove, A. K. Jacobs, J. Ward Kennedy, D. Kereiakes, M. J. Kern, R. E. Kuntz, J. J. Popma, H. V. Schaff, D. O. Williams, et al. ACC/AHA guidelines for percutaneous coronary intervention (revision of the 1993 PTCA guidelines): A report of the American College of Cardiology/ American Heart Association Task Force on practice guidelines (Committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty) endorsed by the Society for Cardiac Angiography and Interventions J. Am. Coll. Cardiol., June 15, 2001; 37(8): 2239 - 2239. [Full Text] [PDF]
|
|
|
|
|
|
S. A. J. Chamuleau, M. Meuwissen, B. L. F. van Eck-Smit, K. T. Koch, A. de Jong, R. J. de Winter, C. E. Schotborgh, M. Bax, H. J. Verberne, J. G. P. Tijssen, et al. Fractional flow reserve, absolute and relative coronary blood flow velocity reserve in relation to the results of technetium-99m sestambi single-photon emission computed tomography in patients with two-vessel coronary artery disease J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1316 - 1322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Langerak, P. Kunz, H. W. Vliegen, H. J. Lamb, J. W. Jukema, E. E. van der Wall, and A. de Roos Improved MR Flow Mapping in Coronary Artery Bypass Grafts during Adenosine-induced Stress Radiology, February 1, 2001; 218(2): 540 - 547. [Abstract] [Full Text]
|
|
|
|
|
|
K. L. Gould, Y. Nakagawa, K. Nakagawa, S. Sdringola, M. J. Hess, M. Haynie, N. Parker, N. Mullani, and R. Kirkeeide Frequency and Clinical Implications of Fluid Dynamically Significant Diffuse Coronary Artery Disease Manifest as Graded, Longitudinal, Base-to-Apex Myocardial Perfusion Abnormalities by Noninvasive Positron Emission Tomography Circulation, April 25, 2000; 101(16): 1931 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. De Bruyne, N. H. J. Pijls, G. R. Heyndrickx, D. Hodeige, R. Kirkeeide, and K. L. Gould Pressure-Derived Fractional Flow Reserve to Assess Serial Epicardial Stenoses : Theoretical Basis and Animal Validation Circulation, April 18, 2000; 101(15): 1840 - 1847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Kern Coronary Physiology Revisited : Practical Insights From the Cardiac Catheterization Laboratory Circulation, March 21, 2000; 101(11): 1344 - 1351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jeremias, S. D. Filardo, R. J. Whitbourn, R. S. Kernoff, A. C. Yeung, P. J. Fitzgerald, and P. G. Yock Effects of Intravenous and Intracoronary Adenosine 5'-Triphosphate as Compared With Adenosine on Coronary Flow and Pressure Dynamics Circulation, January 25, 2000; 101(3): 318 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M POULLIS Coronary pressure measurements: catheter induced errors Heart, November 1, 1999; 82(5): 644a - 645. [Full Text]
|
|
|
|
|
|
C J Vrints, M J Claeys, J Bosmans, V Conraads, and J P Snoeck Effect of stenting on coronary flow velocity reserve: comparison of coil and tubular stents Heart, October 1, 1999; 82(4): 465 - 470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Takagi, Y. Tsurumi, Y. Ishii, K. Suzuki, M. Kawana, and H. Kasanuki Clinical Potential of Intravascular Ultrasound for Physiological Assessment of Coronary Stenosis : Relationship Between Quantitative Ultrasound Tomography and Pressure-Derived Fractional Flow Reserve Circulation, July 20, 1999; 100(3): 250 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Abizaid, G. S. Mintz, R. Mehran, A. Abizaid, A. J. Lansky, A. D. Pichard, L. F. Satler, H. Wu, C. Pappas, K. M. Kent, et al. Long-Term Follow-Up After Percutaneous Transluminal Coronary Angioplasty Was Not Performed Based on Intravascular Ultrasound Findings : Importance of Lumen Dimensions Circulation, July 20, 1999; 100(3): 256 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nishioka, A. M. Amanullah, H. Luo, H. Berglund, C.-J. Kim, T. Nagai, N. Hakamata, S. Katsushika, A. Uehata, B. Takase, et al. Clinical validation of intravascular ultrasound imaging for assessment of coronary stenosis severity: Comparison with stress myocardial perfusion imaging J. Am. Coll. Cardiol., June 1, 1999; 33(7): 1870 - 1878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Scanlon, D. P. Faxon, A.-M. Audet, B. Carabello, G. J. Dehmer, K. A. Eagle, R. D. Legako, D. F. Leon, J. A. Murray, S. E. Nissen, et al. ACC/AHA guidelines for coronary angiography: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Coronary Angiography) developed in collaboration with the Society for Cardiac Angiography and Interventions J. Am. Coll. Cardiol., May 1, 1999; 33(6): 1756 - 1824. [Full Text] [PDF]
|
|
|
|
|
|
C. E. E. Hanekamp, J. J. Koolen, N. H. J. Pijls, H. R. Michels, and H. J. R. M. Bonnier Comparison of Quantitative Coronary Angiography, Intravascular Ultrasound, and Coronary Pressure Measurement to Assess Optimum Stent Deployment Circulation, March 2, 1999; 99(8): 1015 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. W. Bech, N. H. J. Pijls, B. De Bruyne, K. H. Peels, H. R. Michels, H. J. R. M. Bonnier, and J. J. Koolen Usefulness of Fractional Flow Reserve to Predict Clinical Outcome After Balloon Angioplasty Circulation, February 23, 1999; 99(7): 883 - 888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N H J Pijls and B De Bruyne Coronary pressure measurement and fractional flow reserve Heart, December 1, 1998; 80(6): 539 - 542. [Full Text]
|
|
|
|
|
|
D. Baumgart, M. Haude, G. Goerge, J. Ge, S. Vetter, N. Dagres, G. Heusch, and R. Erbel Improved Assessment of Coronary Stenosis Severity Using the Relative Flow Velocity Reserve Circulation, July 7, 1998; 98(1): 40 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. H.J. Pijls, B. de Bruyne, K. Peels, P. H. van der Voort, H. J.R.M. Bonnier, J. Bartunek, and J. J. Koolen Measurement of Fractional Flow Reserve to Assess the Functional Severity of Coronary-Artery Stenoses N. Engl. J. Med., June 27, 1996; 334(26): 1703 - 1708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsuo, S. Watanabe, T. Kadosaki, T. Yamaki, S. Tanaka, S. Miyata, T. Segawa, Y. Matsuno, M. Tomita, and H. Fujiwara Validation of Collateral Fractional Flow Reserve by Myocardial Perfusion Imaging Circulation, March 5, 2002; 105(9): 1060 - 1065. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||