Download Comparison of Fractional Flow Reserve Assessment With Demand

Coronary Artery Disease
Comparison of Fractional Flow Reserve Assessment With
Demand Stress Myocardial Contrast Echocardiography in
Angiographically Intermediate Coronary Stenoses
Juefei Wu, MD; David Barton, MD; Feng Xie, MD; Edward O’Leary, MD; John Steuter, MD;
Gregory Pavlides, MD; Thomas R. Porter, MD
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Background—Real-time myocardial contrast echocardiography (RTMCE) directly measures capillary flow (CBF), which
in turn is a major regulator of coronary flow and resistance during demand or hyperemic stress. Although fractional
flow reserve (FFR) was developed to assess the physiological relevance of an epicardial stenosis, it assumes maximal
microvascular vasodilation and minimal resistance during vasodilator stress. Therefore, we sought to determine the
relationship between CBF assessed with RTMCE during stress echocardiography and FFR in intermediate coronary
lesions.
Methods and Results—Sixty-seven vessels with 50% to 80% diameter stenoses by quantitative coronary angiography in
58 consecutive patients were examined with FFR and RTMCE (mean age, 60±13 years). RTMCE was performed using
an incremental dobutamine (n=32) or exercise (n=26) stress protocol, and myocardial perfusion was assessed using a
continuous infusion of ultrasound contrast. The presence or absence of inducible perfusion defects and wall motion
abnormalities were correlated with FFR. Mean percent diameter stenosis was 60±9%. Eighteen stenoses (27%) had an
FFR ≤ 0.8. Although 17 of the 18 stenoses that were FFR+ had abnormal CBF during RTMCE, 28 of the 49 stenoses
(57%) that were FFR had abnormal CBF, and 24 (49%) had abnormal wall motion in the corresponding coronary artery
territory during stress echocardiography.
Conclusions—In a significant percentage of intermediate stenoses with normal FFR values, CBF during demand
stress is reduced, resulting in myocardial ischemia. (Circ Cardiovasc Imaging. 2016;9:e004129. DOI: 10.1161/
CIRCIMAGING.116.004129.)
Key Words: coronary artery disease ◼ coronary angiography ◼ dobutamine ◼ myocardial ischemia
◼ perfusion imaging
M
aximal hyperemic coronary flow begins to decrease
as stenosis severity exceeds 50% in diameter.1 At
this point, a coronary stenosis is considered functionally
significant. Although one might assume that the regulation
of hyperemic coronary flow in this setting is primarily controlled by stenosis, it is also regulated by microvascular and
capillary resistance.2–4 Detection of functionally significant
coronary artery disease (CAD) has become increasingly
important, as large clinical trials have demonstrated outcome
(death, nonfatal myocardial infarction, and need for urgent
revascularization) is related to functional significance of a
stenosis and not anatomic appearance.5,6 However, detecting
functional significance requires a technique that can accurately examine and quantify the mediators of coronary flow
during stress. Real-time myocardial contrast echocardiography (RTMCE) is a technique that utilizes ultrasound contrast
for the simultaneous analysis of myocardial perfusion and
wall motion (WM) during stress echocardiography.7,8 This
perfusion technique measures capillary blood flow (CBF)
and volume, and thus can indirectly assess capillary microvascular resistance.2,3 Previous studies have shown that the
detection of CBF abnormalities identified with RTMCE during stress echocardiography improve the ability of echocardiography to predict patient outcome during both demand
and vasodilator stress.9,10
See Editorial by Kern and Seto
See Clinical Perspective
Intracoronary pressure–derived fractional flow reserve
(FFR) provides physiologically relevant information in determining the functional significance of a coronary stenosis,
but provides no data regarding CBF.6,11,12 An FFR-guided
approach for revascularization is associated with improved
clinical outcomes in multivessel CAD,6 and abnormal values with this technique clearly identify a higher risk subgroup of patients. Although they do not seem to benefit from
Received January 26, 2016; accepted June 23, 2016.
From the Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (J.W.); Department of Cardiology,
Internal Medicine, University of Nebraska Medical Center, Omaha (D.B., F.X., E.O’L., G.P., T.R.P.); and Nebraska Heart, Lincoln (J.S.).
The Data Supplement is available at http://circimaging.ahajournals.org/lookup/suppl/doi:10.1161/CIRCIMAGING.116.004129/-/DC1.
Correspondence to Thomas R. Porter, MD, Division of Cardiology, 982265 Nebraska Medical Center, Omaha, NE 68198. E-mail [email protected]
© 2016 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org
1
DOI: 10.1161/CIRCIMAGING.116.004129
2 Wu et al Comparing Stress Perfusion Imaging With FFR
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percutaneous coronary interventions, patients with normal
values for FFR (>0.8) in these studies still had relatively high
event rates,6 with death and nonfatal myocardial infarction
rates of ≈2% at <1-year follow up and 4% requiring revascularization. These event rates are worse than those observed
after negative RTMCE stress studies.9,10 With noncritical coronary stenoses during hyperemic stress, capillary resistance has
been shown to play a greater role than stenosis resistance in
regulating coronary blood flow.2 Because RTMCE can visualize abnormalities in capillary resistance as perfusion defects
during hyperemic stress,3 we hypothesized that these perfusion abnormalities may be observed in patients during stress
imaging despite having FFR values that would still be considered normal. The purpose of this project was to determine the
frequency with which FFR and demand stress measurements
of myocardial blood flow and function are discrepant in a
selected group of patients with intermediate coronary stenoses
at quantitative coronary angiography (QCA).
Methods
Study Population
The University of Nebraska Medical Center Institutional Review
Board approved this retrospective study (IRB493-15-FB) and informed consent was waived. Fifty-eight consecutive patients who
underwent both stress RTMCE and coronary angiography with FFR
measurement within 1 month at the University of Nebraska Medical
Center from Jan 2007 to June 2015 were analyzed. All patients were
referred first for an exercise or dobutamine stress RTMCE for suspicion of significant CAD based on the patient’s symptoms. The decision to proceed to angiography was based on both symptoms and the
results of the RTMCE study. Subsequent angiograms all had to have
one 50% to 80% stenosis in a major epicardial artery as determined
by QCA. Exclusion criteria included those with known hypersensitivity to contrast agents, pregnancy or breast feeding, or inadequate
apical windows to analyze myocardial perfusion in 2 contiguous segments of the selected coronary artery territory. We reviewed all clinically available records to ensure that patients with prior myocardial
infarction based on cardiac biomarker criteria were excluded and excluded any coronary artery territory that had a resting WM abnormality detected during the resting contrast infusion.
Quantitative Coronary Angiography and FFR
Coronary angiography was performed as per standard practice via
either femoral or radial approach. The pressure wire (Pressure Wire
5; Radi Medical Systems, Uppsala, Sweden) was calibrated and electronically equalized with the aortic pressure before being placed in the
distal third of the coronary artery being interrogated. Intracoronary nitroglycerin (100 μg) was injected before adenosine infusion to prevent
vasospasm. Intravenous adenosine was administered (140 μg/kg per
minute) through an intravenous line in the antecubital fossa. At steadystate hyperemia, FFR was recorded on the RadiAnalyzer Xpress (Radi
Medical Systems), calculated by dividing the mean coronary pressure
measured with the pressure sensor placed distal to the stenosis by the
mean aortic pressure measured through the guide catheter. This procedure was repeated for all major epicardial arteries with ≥50% stenoses. An FFR value of ≤0.8 was chosen as the cut off for abnormal
based on previous multicenter studies.5 Caffeine and all food products
were held in patients for 12 hours before FFR measurements.
Quantitative Coronary Angiography
Quantitative coronary analysis was performed by an experienced interventional cardiologist (E.O. or D.B.) unaware of the results of the
stress echocardiogram. Any visually evident stenosis was measured
using a handheld electronic caliper (Tesa SA, Renes, Switzerland)
operated with custom-developed software. Measurements were expressed as the percentage diameter narrowing using the diameter of
the nearest normal-appearing region as the reference. An intermediate
coronary stenosis for this study was defined as ≥50% to 80% luminal
diameter stenosis in one major coronary artery or one of its major
epicardial branches, which were the majority of stenoses studied by
FAME II investigators.6
Imaging Techniques With Ultrasound Contrast
The contrast agent used for the study was the commercially available lipid-encapsulated microbubble, Definity (Lantheus Medical
Imaging, North Billerica, MA). This agent was administered as a
3% intravenous continuous infusion at 4 to 6 mL/min under resting
conditions and during stress, with the infusion beginning 1 minute
before acquisition of stress images. RTMCE was performed using
ultrasound scanners equipped with low mechanical index real-time
pulse sequence schemes.8–13 This utilized a mechanical index of <0.2,
frame rates of 20 to 25 H, time gain compensation higher in the near
field, focus at the mitral valve plane or below, and overall gain settings adjusted so that brief high mechanical index impulses uniformly
clear the myocardial segments of any signals.
The decision to perform dobutamine or exercise treadmill stress
echocardiography was made by the referring physician based on patient’s ability to exercise. In either case, patients were instructed to
discontinue β-blocker drugs 24 hours before the stress test. Patients
undergoing treadmill stress underwent maximal symptom-limited
exercise according to the Bruce protocol. Patients undergoing dobutamine stress echocardiography received intravenous dobutamine at a
starting dose of 5 μ/kg per minute, followed by increasing doses of
10, 20, 30, 40, up to a maximal dose of 50 μ/kg per minute, in 3- to
5-minute stages. Atropine (up to 2.0 mg) was injected in patients not
achieving 85% of the predicted maximal heart rate. Only coronary
artery territories with inducible defects but normal resting WM and
CBF were used for comparisons with FFR measurements.
CBF Analysis With RTMCE
All RTMCE studies were analyzed by independent experienced
reviewers (T.R.P. or F.X.) who were blinded to angiographic and
FFR data. These experienced reviewers have interpreted over 1000
RTMCE studies. Perfusion and WM were both assessed using a
17-segment model with coronary artery territory assignments based
on this same consensus model.13 Both CBF and WM were analyzed
simultaneously during the replenishment phase of contrast after brief
high mechanical index impulses, as previously described,9,10 at baseline and at peak stress (defined as >85% of predicted maximum heart
rate). A CBF abnormality during stress imaging was defined as a delay in subendocardial or transmural myocardial contrast replenishment of >2 seconds after a high mechanical index impulse that was
in 2 contiguous segments, and which exhibited normal replenishment
under resting conditions.
Statistical Analysis
All values for FFR and stenosis severity are presented as mean±SD.
No adjustments were made for multiple vessels within individuals in
the per-vessel analysis. Sensitivity and specificity of CBF analysis
with RTMCE were analyzed for detecting stenoses with FFR values
of ≤0.8. Differences in stenosis severity between vessels with abnormal versus normal FFR values were compared with unpaired t testing.
Contingency tables were constructed to determine if the proportion
of times an abnormal FFR study was associated with an abnormal
RTMCE study was significantly different than the proportion of times
a normal FFR study was associated with a normal RTMCE study. A
Fisher exact test was used for this comparison. In all comparisons, a
P<0.05 was considered significant.
Results
A total of 67 vessels in 58 patients with 1 stenosis defined
by quantitative angiography to be 50% to 80% diameter were
3 Wu et al Comparing Stress Perfusion Imaging With FFR
Table 1. Baseline Characteristics*
Parameter
Total Patients (n=58)
Age, y
60±13
Women
22 (38%)
Family Hx of CAD
32 (55%)
Smoker
20 (34%)
Hyperlipidemia
44 (76%)
Diabetes mellitus
22 (38%)
HTN
45 (78%)
Previous PTCA
22 (38%)
Ejection fraction
57±11%
Medications
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β blockers
40 (69%)
ACE inhibitors or ARB
31 (53%)
Aspirin
47 (81%)
Statin
40 (69%)
Nitrates
10 (17%)
Stress echo data
Peak heart rate, bpm
142±16
Peak systolic blood pressure, mm Hg
156±36
Peak rate pressure product
22 219±6116
Angiographic data
No. of patients Single-vessel stenoses
50
No. of patients two-vessel stenoses
7
No. of patients three-vessel stenoses
1
*Values presented are mean and percentages for continuous variables, and n
(%) for categorical variables.
ACE indicates angiotensin-converting-enzyme inhibitor; ARB, angiotensin II
receptor blockers; CAD, coronary artery disease; HTN, hypertension; and PTCA,
percutaneous transluminal coronary angioplasty.
evaluated (mean age, 60±13 years; 22 women). Patient characteristics are summarized in Table 1.
Real-Time Myocardial Contrast Echocardiography
Of the 67 vessels with 50% to 80% diameter stenoses, 45 (67%)
exhibited abnormal CBF in the subtended coronary artery territory with RTMCE. CBF abnormalities in multiple coronary
artery territories were evident in 2 patients (Table 2). Thirty-six of
the 45 coronary artery territories with inducible perfusion defects
(80%) also had inducible WM abnormalities (ischemia). Thirtyone territories involved the left descending artery, 9 involved left
circumflex artery territories, and 5 involved the right coronary
artery. Mean QCA-derived stenosis severity in the territories that
were abnormal with RTMCE was 60±9%, whereas it was 59±9%
in the territories that were negative with RTMCE (P=0.82).
Fractional Flow Reserve and Quantitative
Angiography
FFR readings ranged from 0.55 to 1.00 (mean, 0.86±0.11). A
total of 18 vessels (27%) had FFR values ≤0.8, 15 in the left
anterior descending coronary artery, and 3 in the right coronary
artery territories. Figure 1 demonstrates how percent diameter
stenosis severity by quantitative angiography correlated with
FFR results. Mean QCA stenosis severity in the territories that
were positive with FFR was 63±10% and 58±8% in the territories that were negative with FFR, respectively (P=0.029).
RTMCE Versus FFR
Seventeen of the 18 vessels (93%) with abnormal FFR values had abnormal CBF (Table 3). However, in 28 vessels
(57%), FFR was considered normal despite the presence of an
induced perfusion defect in the territory (examples are shown
in Figures 2 and 3 for the right coronary and left anterior
descending territories, respectively). Inducible WM abnormalities (ischemia) were observed in 24 of these 28 territories.
The FFR values in the vessels with abnormal perfusion but
normal WM (0.85±0.10) were not different from those with
both abnormal perfusion and WM (0.84±0.12; P=0.71). In the
FFR vessels that had values >0.80, there were no differences
in FFR values for those with normal RTMCE studies versus
abnormal RTMCE studies (Figure 4). There was a significant
difference in the proportion of times an abnormal FFR study
was associated with an abnormal RTMCE study and the proportion of times a normal FFR study was associated with a
normal RTMCE study (P=0.003, Fisher exact test).
Follow-up was possible in 26 of the 27 patients (total of 28
vessels) who had abnormal CBF with RTMCE but had negative
FFR values at the time of the corresponding angiogram. Median
duration of follow-up was 2 months (range, 1–16 months). One
patient could not be reached by phone and medical records
were unavailable. Sixteen patients (59%) still had Canadian
Cardiovascular Functional Class II–III symptoms or had revascularization of the coronary artery because of compelling symptoms. Ten patients remained asymptomatic on medical therapy.
Discussion
This is the first study to examine the relationship between CBF
assessments during demand stress in myocardial territories
supplied by coronary arteries with exclusively intermediate
Table 2. RTMCE and FFR Test Results
RTMCE Test Results
Total patients (territories)
58 (67)
Abnormal territory result
45
Normal territory result
22
Location of l Abnormal Territories
45
LAD
31
RCA
5
LCX
9
FFR results
Total patients (vessels)
58 (67)
FFR > 0.8 (vessels)
41 (49)
FFR ≤0.8 (vessels)
1718
FFR indicates fractional flow reserve; LAD, left anterior descending coronary
artery; LCX, left circumflex coronary artery; RCA, right coronary artery; and
RTMCE, real-time myocardial contrast echocardiography.
4 Wu et al Comparing Stress Perfusion Imaging With FFR
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Figure 1. The relationship between fractional flow reserve (FFR)
values and coronary stenosis severity by quantitative angiography. ○ represent FFR values that were considered abnormal,
whereas ● represent FFR values that were considered normal.
stenoses (50%–80% by quantitative angiography) and a range
of both normal and abnormal FFR values. It confirms that
abnormal CBF during demand stress RTMCE not only has
high sensitivity for detecting a significant pressure gradient
across a coronary stenosis but also demonstrates that abnormal CBF and WM occur in a sizable percentage of cases
where FFR of the supplying vessel is considered normal.
Previous studies have demonstrated the incremental
diagnostic value of myocardial perfusion imaging over WM
analysis during stress in both the detection of angiographic
disease by angiography and in predicting patient outcome.9,10
These clinical studies have validated animal studies which
demonstrated that CBF changes become visually evident
with myocardial contrast echocardiography earlier in the
stress test than WM.14 During stress imaging, CBF, as measured by RTMCE, is a major regulator of coronary flow
in the upstream circuit, which includes epicardial vessels,
prearterioles and arterioles. Although intuitively one would
think that epicardial stenosis is the primary location of coronary blood flow regulation during stress, it has actually been
shown to be more related to the microvascular resistance at
the capillary level when an intermediate stenosis is present.2–4
Sen et al15 demonstrated that in ranges of intermediate FFR
values (0.6–0.9), microvascular resistance was more variable when compared with Instantaneous Wave-Free Ratio
suggesting a variable response to adenosine by the arterioles
or an inability to achieve true hyperemia in this setting. This
variability has also been observed in studies comparing FFR
to coronary flow reserve, where reductions in flow reserve
occurred in instances where FFR values were normal.4,16 In
these studies, low coronary flow with increased microvascular resistance was observed in vessels that had discordantly
high or normal FFR values. Abnormalities in coronary blood
flow reserve measured with transthoracic Doppler have been
observed in patients with intermediate stenoses (5±65%)
who had FFR values >0.8.17 On the contrary, quantitative
measurements of coronary blood flow reserve in patients
have correlated closely with CBF changes, both in the
presence or absence of intermediate epicardial stenoses.18
Therefore, we hypothesize that in some instances where
microvascular resistance is not minimized, or potentially
increased, that FFR measurements may be falsely negative
in patients with clinically relevant demand ischemia. This
suggests that the distal pressure measured with FFR is influenced not only by the gradient across the epicardial stenosis
but also by the resistance of the downstream vessels. Only
with more severe forms of epicardial stenoses does FFR
become less variable likely because of a more uniform resistance within the microvasculature.2,16 In our study, we did
note that stenosis severity was worse in those with abnormal
FFR values (Figure 1).
This may explain why an abnormal FFR value has been
shown to identify patients at highest risk for events,6,11,12 as
it clearly identifies the most severe spectrum of obstructive
lesions from a functional standpoint. However, a normal FFR
value, when defined as >0.8, may underestimate the physiological and clinical relevance of anatomically less severe
stenoses. As our study showed, there was even inducible ischemia (ie, WM abnormality) in the coronary artery territories
subtended by vessels that had FFR values >0.8 and a 50%
to 80% diameter stenosis by quantitative angiography. This
failure of FFR to identify certain physiologically relevant
intermediate coronary stenoses may explain the differences
in clinical outcome observed in trials utilizing FFR to guide
CAD management versus those utilizing RTMCE. The large
multicenter studies examining FFR as a guide to management
in patients with stable angina still had annual event rates of
3% in their normal registries,6 which are significantly higher
than the 1% annual event rates in similar patients after normal
stress RTMCE studies.9,10
Correlation With Other Comparative Studies
When examining noninvasive correlations with FFR, magnetic resonance imaging (MRI) utilizing first-pass bolus
injections of gadolinium contrast have demonstrated excellent sensitivities and specificities for detecting vessels with
FFR values < 0.75.19 However, these studies included >
over 40% of patients without angiographic CAD, as well
as patients having coronary vessels in which there was a
subtotal or total occlusion. Other adenosine magnetic resonance studies examining correlations of myocardial perfusion reserve with FFR exclusively in vessels that were >50%
stenosed have demonstrated similar findings to the current
study (93% sensitivity, 57% specificity in the study by Costa
et al20). Chiribiri et al21 did improve specificity for detection
Table 3. Concordance Between RTMCE and FFR in Vessels
With Coronary Stenoses Between 50% to 80% Diameter by
Quantitative Angiography
FFR+
FFR–
RTMCE+
17
28
RTMCE–
1
21
FFR indicates fractional flow reserve and RTMCE, real-time myocardial
contrast echocardiography.
5 Wu et al Comparing Stress Perfusion Imaging With FFR
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Figure 2. An example of an inducible inferior perfusion defect (arrows) during dobutamine stress real time myocardial contrast echocardiography. Subsequent quantitative coronary angiography (right panel) demonstrated a 56% diameter stenosis (black arrows), and an
fractional flow reserve value across this stenosis of 0.94. (Movie I in the Data Supplement).
of abnormal FFR during adenosine MRI by examining for a
visually evident transmural perfusion gradient, but this also
included vessels with high grade stenoses or total occlusions.
Despite adding these severely stenosed vessels, the positive
predictive value of a visually evident subendocardial perfusion defect was still <80%. It is also important to emphasize
that perfusion defects observed with RTMCE during demand
stress reflect myocardial blood flow changes, whereas those
seen with vasodilator stress MRI or Technesium-based radionuclide imaging reflect myocardial blood volume changes.
Myocardial blood flow reductions are observed before myocardial blood volume changes in significant CAD,3 and this
difference in sensitivity may explain why FFR correlates
slightly better with vasodilator stress MRI or Technesium–
based vasodilator stress.perfusion techniques.
Study Limitations
Our results represent a single-center retrospective study
involving 58 patients having RTMCE before the catheterization procedure. If we treat the summary statistics in Figure 3 as
population parameters for designing a new prospective study
which starts with the basic conclusions from the current study,
then a power calculation for the sample size of the current
study using a 1-sided exact Fisher exact test would be over
0.90. However, with retrospective studies, selection bias may
affect results, and therefore prospective studies are needed
to test both the correlation of CBF with FFR in intermediate
stenoses, and what impact an abnormal CBF finding during
demand stress with normal FFR has on patient outcome.
The time period over which these studies were performed
was long because of the slow increase in the use of FFR to
examine intermediate stenosis at our institution. During this
time period the use of FFR was primarily in those with no
prior stress echocardiography data before their diagnostic
angiogram. However, the purpose of the study was to determine the frequency with which an abnormal demand CBF
study correlates with FFR measurements of physiological relevance in vessels with a 50% to 80% diameter stenosis, not to
publish data on overall sensitivity and specificity of RTMCE
in this setting. In this context, it is important to note that
FFR was only measured in vessels which had an intermediate range of stenosis severity. Other studies comparing FFR
Figure 3. An example of an inducible apical perfusion defect and wall motion abnormality during dobutamine stress with real-time myocardial contrast echocardiography. Subsequent coronary angiography demonstrated a >50% diameter proximal left anterior descending
lesion (right; black arrows), but fractional flow reserve was measured to be only 0.84. (Movie II in the Data Supplement).
6 Wu et al Comparing Stress Perfusion Imaging With FFR
number of atherosclerotic lesions in the 50% to 80% diameter
range have not been intervened on.6 Our study demonstrates
that relying on FFR alone in evaluating these intermediate
level stenoses may require further consideration if the territories they subtend exhibit inducible ischemia or CBF abnormalities during demand stress.
Acknowledgments
We thank Carol Gould for her administrative assistance with the preparation of the manuscript, and Robin High, PhD, for his statistical
comments regarding the power calculation.
Sources of Funding
This project was supported in part by the Theodore F. Hubbard
Foundation, Omaha, NE.
Disclosures
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Figure 4. Box Wistar plots comparing the normal fractional flow
reserve values in the coronary artery territories that had normal
real-time myocardial contrast echocardiography studies compared with those with abnormal real-time myocardial contrast
echocardiography studies. The box contains the 25% to 75%
percentiles; the bars contain the range of values. There were no
significant differences between these groups (P=0.23).
with perfusion imaging techniques have included vessels with
minimal or no disease in the vascular territory,17 as well as
vessels with more severe stenoses including coronary occlusions. This would naturally improve the agreement between
techniques, but would not help us understand whether important clinically relevant disagreement exists in the evaluation of
an intermediate stenosis.
Our study was performed to simulate real-world practice,
where FFR is currently being utilized to evaluate and guide
management in intermediate level stenoses. However, we
did have a higher prevalence of diabetics and smokers when
compared with other clinical trials, and these risk factors may
increase the likelihood of stress-induced microvascular abnormalities. It is in this setting where equipoise is needed to consider the potential role of capillary contributions to coronary
blood flow abnormalities when FFR is found to be >0.8.
Finally, although patients were held without food or water
for 12 hours before the procedure, no specific policies were in
place to restrict caffeine use for 24 hours before FFR measurements. It is possible that this led to higher FFR values.22
Conclusions
Our findings confirm that abnormal CBF with RTMCE has
high sensitivity for detecting an abnormal FFR of an intermediate stenosed vessel subtending the abnormal myocardial territory. A normal FFR value, however, has a low sensitivity in
predicting normal CBF by RTMCE. This might reflect microvascular abnormalities which are a significant pathophysiologic mechanism by which myocardial ischemia is produced
in patients with moderate epicardial stenoses.
An FFR-based strategy has been shown to be preferable
to an invasive anatomic approach in deciding when lesions
should be revascularized. By revascularizing only those atherosclerotic coronary arteries with FFR<0.8, a significant
Dr Porter has received research support from Lantheus Medical
Imaging and Astellas Pharma, Inc. He has received instrumentation and research support from Philips Research North America and
General Electric Global Research. The other authors have no conflicts
of interest to disclose.
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CLINICAL PERSPECTIVE
This study demonstrated that, although fractional flow reserve measurements of coronary stenosis that are 50% to 80% in
diameter have been useful for identifying high risk lesions, a normal value may be present in a large number of patients who
exhibit inducible ischemia with demand stress testing (dobutamine or exercise stress). Abnormal perfusion defects and wall
motion abnormalities during dobutamine or exercise stress detected with real time myocardial contrast echocardiography
were seen in >50% of lesions that had 50% to 80% diameter stenoses in the subtended vessel despite having normal fractional flow reserve. Further study is needed to determine the clinical outcome of these patients.
Comparison of Fractional Flow Reserve Assessment With Demand Stress Myocardial
Contrast Echocardiography in Angiographically Intermediate Coronary Stenoses
Juefei Wu, David Barton, Feng Xie, Edward O'Leary, John Steuter, Gregory Pavlides and
Thomas R. Porter
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Circ Cardiovasc Imaging. 2016;9:
doi: 10.1161/CIRCIMAGING.116.004129
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Movie Legends
Movie Legend 1. Example of an inducible inferior perfusion defect and wall thickening
ab normality in a patient with a right coronary stenosis that had an FFR value of 0.94.
Movie Legend 2. Example of an inducible apical perfusion defect in a patient with a left
anterior descending stenosis that had an FFR value of 0.84.