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Coronary Hemodynamics
Diagnostic Accuracy of Combined Intracoronary Pressure
and Flow Velocity Information During Baseline Conditions
Adenosine-Free Assessment of Functional Coronary Lesion Severity
Tim P. van de Hoef, MD; Froukje Nolte, MSc; Peter Damman, MD; Ronak Delewi, MD;
Matthijs Bax, MD; Steven A.J. Chamuleau, MD, PhD; Michiel Voskuil, MD, PhD;
Maria Siebes, PhD; Jan G.P. Tijssen, PhD; Jos A.E. Spaan, PhD;
Jan J. Piek, MD, PhD; Martijn Meuwissen, MD, PhD
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Background—The assessment of functional coronary lesion severity using intracoronary physiological parameters such
as coronary flow velocity reserve and the more widely used fractional flow reserve relies critically on the establishment
of maximal hyperemia. We evaluated the diagnostic accuracy of the stenosis resistance index during nonhyperemic
conditions, baseline stenosis resistance index, compared with established hyperemic intracoronary hemodynamic
parameters, because achievement of hyperemia can be cumbersome in daily clinical practice.
Methods and Results—A total of 228 patients, including 299 lesions (mean stenosis diameter 55%±11%), underwent
myocardial perfusion scintigraphy for documentation of reversible perfusion defects. Distal coronary pressure and
flow velocity were assessed with sensor-equipped guidewires during baseline and maximal hyperemia, induced by an
intracoronary bolus of adenosine (20–40 μg). We determined stenosis resistance (SR) during baseline and hyperemic
conditions as well as fractional flow reserve and coronary flow velocity reserve. The discriminative value for myocardial
ischemia on myocardial perfusion scintigraphy of all parameters was compared using receiver-operating-characteristic
curves. Baseline SR showed good agreement with myocardial perfusion scintigraphy. The diagnostic performance of
baseline SR (area under the curve, 0.77; 95% CI, 0.71–0.83) was as accurate as fractional flow reserve and coronary
flow velocity reserve (area under the curve, 0.77; 95% CI, 0.71–0.83 and area under the curve, 0.75; 95% CI, 0.68–0.81
respectively; P>0.05 compared with baseline SR for both). However, hyperemic SR, combining both pressure and
flow velocity information during hyperemia, was superior to all other parameters (area under the curve, 0.81; 95% CI,
0.76–0.87; P<0.05 compared with all other parameters).
Conclusions—Combined pressure and flow velocity measurements during baseline conditions may provide a useful tool for
functional lesion severity assessment without the need for potent vasodilators. (Circ Cardiovasc Interv. 2012;5:508-514.)
Key Words: coronary artery disease ◼ coronary flow reserve ◼ fractional flow reserve ◼ hemodynamics
◼ physiology
A
dequate patient selection for percutaneous coronary
intervention is of utmost importance to avoid unnecessary complications. Consequently, objective evidence for
myocardial ischemia is mandatory for optimal management of patients with coronary artery disease, in particular in
patients with coronary lesions of intermediate severity (40%–
70% diameter stenosis on coronary angiography).1,2 The use
of sensor-equipped guidewires for the assessment of functional coronary lesion severity has emerged as a standard diagnostic modality to provide objective evidence of myocardial
ischemia during cardiac catheterization.3,4 The indices derived
from pressure or flow velocity measurements, fractional flow
reserve (FFR) and coronary flow velocity reserve (CFVR),
respectively, show a high agreement with noninvasive stress
testing.5,6 Interpretation in individual cases may, however, be
cumbersome. Because these indices are based on either intracoronary pressure or flow velocity, they do not differentiate
between hemodynamic properties of the epicardial stenosis and the distal microvasculature,7,8 potentially leading to
unfounded treatment when a single parameter is determined
or to ambiguous observations when both are assessed.9,10
Combining pressure and flow velocity information, summarized by the hyperemic stenosis resistance index (HSR), was previously shown to improve diagnostic accuracy of intracoronary
Received September 20, 2011; accepted June 6, 2012.
From the Departments of Cardiology (T.P.v.d.H., P.D., R.D., J.G.P.T., J.J.P., M.M.) and Biomedical Engineering & Physics (T.P.v.d.H., F.N., M.S.,
J.A.E.S.), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Cardiology, Haga Teaching Hospital,
The Hague, the Netherlands (M.B.); Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands (S.A.J.C., M.V.); and the
Department of Cardiology, Amphia Hospital, Breda, the Netherlands (M.M.).
Correspondence to Jan J. Piek, MD, PhD, Academic Medical Center, University of Amsterdam, Department of Cardiology, Room B2-250,
Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. E-mail [email protected].
© 2012 American Heart Association, Inc.
Circ Cardiovasc Interv is available at http://circinterventions.ahajournals.org
508
DOI: 10.1161/CIRCINTERVENTIONS.111.965707
van de Hoef et al Adenosine-Free Functional Lesion Severity 509
hemodynamic parameters, especially in these discordant lesions.11
Importantly, where FFR and CFVR rely critically on the establishment of a maximal hyperemic state, accurate assessment of HSR
is less dependent on maximal hyperemia.11
Editorial see p 456
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The use of intracoronary hyperemic agents in the cardiac
catheterization laboratory, per definition required for assessment of FFR, CFVR, or HSR, can however be cumbersome in
daily clinical practice due to their unavailability, time-consumingness, contraindications, or side effects.12,13 Furthermore,
there is an ongoing debate with respect to the dose of agent
needed to achieve maximal hyperemia and the site of administration to be used.14–21 Parameters requiring only baseline conditions could therefore be considered preferable to facilitate
universal use of functional lesion severity assessment before
coronary intervention.
Considering the previously documented high diagnostic
accuracy of HSR for myocardial ischemia as well as the relative independence of HSR on maximal hyperemia, we hypothesized that the stenosis resistance index determined during
baseline conditions has adequate diagnostic accuracy for
functional coronary lesion severity assessment. Therefore, we
compared the diagnostic accuracy of stenosis resistance index
during baseline (BSR) and hyperemic conditions (HSR), as
well as FFR and CFVR for myocardial ischemia assessed by
myocardial perfusion scintigraphy (MPS).
What Is Known
•• The use of intracoronary physiology is important for
guidance of percutaneous coronary intervention.
•• FFR, CFVR, or HSR may be used for this purpose,
but they rely critically on a maximal hyperemic state.
•• The use of potent vasodilators to achieve a maximal
hyperemic state can be cumbersome in daily clinical
practice.
What the Study Adds
•• The BSR, a vasodilator-free parameter, results in
similar diagnostic accuracy for myocardial ischemia
as compared with FFR and CFVR.
•• When the use of potent vasodilators is cumbersome
in daily clinical practice, BSR may provide a useful
tool for stenosis severity assessment.
Methods
Between April 1997 and September 2006, a total of 228 consecutive
patients undergoing elective percutaneous coronary intervention for
stable anginal complaints were included in the study. Patients were
referred for single- or double-vessel coronary artery disease with
at least one intermediate coronary lesion (40%–70% diameter stenosis on visual assessment). Exclusion criteria consisted of: ostial
lesions, ≥2 stenoses in the same coronary artery, severe renal function impairment (sMDRD calculated glomerular filtration rate <30
mL/min/1.73m2), significant left main coronary artery stenosis, atrial
fibrillation, recent myocardial infarction (<6 weeks before screening),
Table 1. Definitions of the Parameters Used
CFVR=hAPV/bAPV
FFR=mean Pdistal/mean Paorta (during hyperemia)
BSR=(Paorta−Pdistal)/bAPV
HSR=(Paorta−Pdistal)/hAPV
CFVR indicates coronary flow velocity reserve; APV, average peak flow
velocity; FFR, fractional flow reserve; Pdistal, distal coronary pressure; Paorta,
aortic pressure; BSR, baseline stenosis resistance index; HSR, hyperemic
stenosis resistance index; b, baseline; h, hyperemia.
prior coronary artery bypass graft surgery, or visible collateral development. The institutional ethics committee approved the study protocol and all patients gave written informed consent.
Myocardial Perfusion Scintigraphy
MPS was performed in all patients with the use of either 99mTechnetium-labeled methoxyisobutylisonitrile or tetrofosmin (Myoview)
according to a standard 2-day stress–rest protocol. Defect reversibility and localization were semiquantitatively determined by a panel of
experienced nuclear medicine physicians, who were blinded to the
angiographic data. Improvement at rest of more than one grade was
considered to be a reversible perfusion defect. The result was considered positive when a reversible defect was allocated to the perfusion
territory of the coronary artery of interest.22
Cardiac Catheterization and
Hemodynamic Measurements
All patients underwent cardiac catheterization within 1 week after
MPS. Quantitative coronary angiography was performed offline to
determine stenosis severity. Percent diameter stenosis was obtained
with the use of a validated automated contour detection algorithm
(QCA-CMS Version 3.32; MEDIS, Leiden, The Netherlands). Distal
coronary pressure and blood flow velocity were assessed with sensorequipped guidewires during baseline conditions and maximal hyperemia, which was induced by an intracoronary bolus of adenosine (20
μg for the right coronary artery and 40 μg for the left coronary artery).
Intracoronary pressure was measured distal to the target lesion with a
0.014-inch pressure-monitoring guidewire (Volcano Corp, San Diego,
CA). Coronary blood flow velocity measurements were performed
directly after pressure measurements using a Doppler-tipped guidewire
(Volcano Corp). Pressure- and flow velocity-derived parameters of
functional coronary lesion severity were: BSR, HSR, FFR, and CFVR.
The definitions of the evaluated parameters are shown in Table 1.
Statistical Analysis
Receiver operating characteristic curves were used to compare the
discriminative value of FFR, CFVR, HSR, and BSR for the presence of reversible perfusion defects by the area under the curve.
Agreement with MPS outcomes was determined for HSR, FFR, and
CFVR based on their respective cutoff values: 0.75 for FFR, 2.0 for
CFVR, and 0.80 mm Hg · cm−1 · sec for HSR. In absence of a clinically
adopted cutoff value, the best cutoff value for BSR was defined as the
highest sum of sensitivity and specificity. This value was subsequently
used to determine agreement with MPS. False-positive and false-negative outcomes, positive and negative predictive value, and sensitivity
and specificity for all parameters were defined according to the MPS
outcomes using the previously mentioned cutoff values. Additionally,
these were evaluated for the more recently adopted cutoff value for
FFR of 0.80. Accuracy for agreement with MPS of all parameters was
compared using the McNemar test. All analyses were performed at
the lesion level. We additionally performed a patient-level analysis by
randomly selecting one lesion per patient. Continuous variables were
expressed as mean (±SD) or median (interquartile range) and comparison was performed using the Student t test or Mann-Whitney U test
where appropriate. Categorical variables were presented as frequencies
510 Circ Cardiovasc Interv August 2012
Table 2. Baseline Patient Characteristics
Table 3. Angiographic and Hemodynamic Lesion Characteristics
N=228
Age, y
Reversible Defect
(n=89)
No Reversible
Defect (n=210)
61±11
52±9
0.0001
Minimal lumen
diameter, mm
1.10±0.42
1.39±0.40
0.0001
Reference vessel
diameter, mm
2.90±0.64
2.92±0.67
0.96
CFVR
0.0001
60±11
Male sex
157 (69)
Coronary risk factors
Cigarette smoking
68 (30)
Hypertension
85 (37)
Positive family history
101 (44)
Hyperlipidemia
135 (59)
Diabetes mellitus
33 (14)
Prior myocardial infarction
83 (36)
Prior coronary intervention
45 (20)
Medication
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Beta-blockers
166 (73)
Nitrates
137 (60)
Calcium antagonists
141 (62)
ACE inhibitors
46 (20)
Lipid-lowering drugs
133 (58)
Aspirin
204 (89)
Data is presented as mean±SD or frequency (%).
ACE indicates angiotensin-converting enzyme.
(percentage) and compared with the χ2 test. A 2-sided α level of 0.05
was considered statistically significant.
Diameter stenosis, %
P Value
1.85±0.73
2.47±0.74
bAPV, cm/sec
15.5±8.9
18.1±7.6
0.0001
hAPV, cm/sec
28.1±17.1
42.4±16.0
0.0001
FFR
0.65±0.19
0.81±0.12
0.0001
hPa, mm Hg
96.6±12.6
95.0±12.3
0.24
hPd, mm Hg
63.0±20.5
77.3±15.5
0.0001
HSR, mm Hg/cm/sec
2.07±2.44
0.60±1.26
0.0001
hdelP, mm Hg
30.0 (18.5–46.5)
15.0 (10.0–23.0)
0.0001
BSR, mm Hg/cm/sec
1.84±2.43
0.54±1.10
0.0001
bPa, mm Hg
99.2±12.8
98.8±12.0
0.75
bPd, mm Hg
79.2±21.4
91.3±13.8
0.0001
13.0 (6.0–31.0)
5.0 (2.0–9.0)
0.0001
bdelP, mm Hg
Data are presented as mean±SD or median (interquartile range).
CFVR indicates coronary flow velocity reserve; APV, average peak flow
velocity; h, hyperemia; b, baseline; FFR, fractional flow reserve; Pa, mean aortic
pressure; Pd, mean distal pressure; HSR, hyperemic stenosis resistance index;
delP, pressure gradient across the stenosis; BSR, baseline stenosis resistance;
DS, diameter stenosis.
Results
Patients
A total of 228 patients (mean age, 60±11 years), including
299 coronary lesions, underwent MPS to determine the presence of reversible perfusion defects. Results for HSR have
been reported previously for 151 patients, including 181
lesions.11 Baseline characteristics of all patients are shown in
Table 2. Quantitative coronary angiography of the 299 lesions
involved yielded a mean diameter stenosis of 55%±11%. MPS
was considered positive in 30% of lesions. Angiographic and
hemodynamic characteristics for lesions with and without
reversible perfusion defects are listed in Table 3.
Discriminative Value
The receiver operating characteristic curves for FFR, CFVR,
HSR, and BSR are visualized in the Figure. Receiver operating characteristic curve analysis yielded the highest diagnostic
accuracy for myocardial ischemia for HSR as shown by the
area under the curve (Table 4), which proved to be significantly higher compared with all other parameters (Table 5).
Notably, the receiver operating characteristic curve of BSR
yielded a similar area under the curve as FFR and CFVR.
Diagnostic Performance
The best cutoff value for BSR was defined as 0.66 mm Hg ·
cm−1 · sec (sensitivity 64%, specificity 80%). Diagnostic accuracy was highest with the use of HSR (P<0.005 compared
with all other parameters). Importantly, diagnostic accuracy
of BSR was similar to both FFR with a cutoff value of 0.75
(P=0.58) and CFVR (P=0.28) and was significantly higher
compared with FFR with a cutoff value of 0.80 (P=0.001;
Table 6). Patient-level analyses yielded similar estimates and
conclusions (data not shown).
Discussion
The use of a parameter based on both intracoronary pressure and blood flow velocity measurements during baseline conditions, BSR, has a similar diagnostic accuracy for
reversible perfusion defects on MPS as compared with the
most frequently used method for coronary stenosis severity
evaluation, FFR. Notably, accuracy of BSR was significantly
higher compared with FFR with the use of 0.80 as a cutoff
value. This novel approach to intracoronary pressure and
flow velocity measurements may provide a useful tool for
vasodilator-free stenosis severity evaluation when the use
of potent vasodilators is cumbersome or contraindicated in
daily clinical practice.
Evaluation of Functional Lesion Severity
Without Hyperemia
Several intracoronary hemodynamic parameters for functional lesion severity assessment during baseline conditions
have been investigated previously. Coronary flow-derived
parameters include the diastolic to systolic velocity ratio and
proximal to distal velocity ratio.23 Both parameters were,
however, shown to have limited diagnostic accuracy for myocardial ischemia when compared with CFVR.24 Pressurederived parameters that have been investigated previously
include the transstenotic pressure gradient during baseline
conditions,25 resting distal pressure to aortic pressure ratio,26
van de Hoef et al Adenosine-Free Functional Lesion Severity 511
Figure. Receiver operator characteristic
curves of fractional flow reserve, coronary
flow velocity reserve, hyperemic stenosis
resistance index (HSR), and baseline stenosis resistance index (BSR). The area under
the curve for HSR was significantly larger
than for all other parameters. The area
under the curve of BSR was similar to that
of FFR or CFVR. FFR indicates fractional
flow reserve; CFVR, coronary flow velocity
reserve.
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and the pulse transmission coefficient.27,28 None of the previously investigated nonhyperemic parameters have been
implemented in clinical practice so far because of limited
diagnostic accuracy or a lack of supportive data.
Most recently, Sen et al29 introduced the instantaneous
wave-free ratio as a vasodilator-free pressure-derived parameter for evaluation of functional lesion severity. This novel
parameter is defined as the distal pressure to aortic pressure
ratio in middiastole during baseline conditions. The authors
postulate that coronary resistance is stable and minimal during a specific time window during middiastole, comparable to
hyperemic microvascular resistance, and therefore the distal
pressure to aortic pressure ratio during this time window is
expected to be similar to FFR. However, the concept of FFR
is based on an assumed linear relationship between pressure
and flow when microvascular resistance is expected to be
minimal, during maximal vasodilation. During baseline conditions, coronary flow is autoregulated, that is, vascular tone is
present, and coronary flow is relatively pressure-independent
within the physiological range of pressures.7 Additionally, it
has been shown at several occasions that diastolic resistance
is not stable.30,31 Hence, the finding that beat-averaged hyperemic resistance equals diastolic resistance in the presence of
Table 4. Diagnostic Accuracy by Area Under the Receiver
Operating Characteristic curves (AUCs)
Ambiguities in FFR and CFVR
As mentioned previously, assessment of both FFR and CFVR
depends critically on the achievement of maximal hyperemia,8,32 which is, at times, not taken into account in daily clinical practice. Furthermore, FFR is per definition determined
when microvascular resistance is lowest and constant, during
maximal vasodilatation. However, when microvascular disease is present or maximal hyperemia is not achieved, microvascular resistance is increased and consequently coronary
Table 5. Differences in Area Under the Receiver Operating
Characteristic Curves (AUCs)
Difference in AUC
P Value
AUC
95% CI
BSR versus FFR
0.00
0.88
0.77
0.71–0.83
BSR versus CFVR
HSR versus FFR
0.02
0.04
0.52
0.005
Parameter
BSR
tone lacks a theoretical basis, and one may wonder whether
instantaneous wave-free ratio has a solid physiological fundament. The authors report that, overall, instantaneous
wave-free ratio correlated well with FFR, but the reported
correlation is predominated by patients with a highly normal
FFR, and correlation within the diagnostically relevant range
of FFR is notably less accurate. Although an interesting novel
parameter, that may well facilitate universal use of coronary
physiology in daily clinical practice, instantaneous wave-free
ratio is still under investigation, and further prospective studies are needed to define its accuracy for detection of myocardial ischemia.
Contrast
HSR
0.81
0.76–0.87
HSR versus CFVR
0.07
0.02
CFVR
0.75
0.68–0.81
HSR versus BSR
0.05
0.007
FFR
0.77
0.71–0.83
FFR versus CFVR
0.02
0.44
BSR indicates baseline stenosis resistance index; HSR, hyperemic stenosis
resistance index; CFVR, coronary flow velocity reserve; FFR, fractional flow
reserve.
HSR indicates hyperemic stenosis resistance index; FFR, fractional flow
reserve; CFVR, coronary flow velocity reserve; BSR, baseline stenosis resistance
index.
512 Circ Cardiovasc Interv August 2012
Table 6. Outcomes Compared With Myocardial
Perfusion Scintigraphy
FFR
Cutoff 0.75
FFR
Cutoff 0.80
CFVR
BSR
HSR
Positive
58 (19)
66 (22)
54 (18)
55 (18)
60 (20)
False-positive
48 (16)
81 (27)
52 (17)
42 (14)
26 (9)
False-negative
31 (10)
23 (8)
35 (12)
32 (11)
29 (10)
Total inaccurate
79 (26)*
87 (29)*
74 (25)*
55 (18)
104 (35)* †
PPV
0.55
0.45
0.51
0.57
0.70
NPV
0.84
0.85
0.82
0.86
0.86
Sensitivity
0.65
0.74
0.61
0.64
0.67
Specificity
0.77
0.61
0.75
0.80
0.88
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Data are presented as frequency (%).
FFR indicates fractional flow reserve; CFVR, coronary flow velocity reserve;
BSR, baseline stenosis resistance index; HSR, hyperemic stenosis resistance
index; PPV, positive predictive value; NPV, negative predictive value.
*P<0.005 compared with HSR.
†P=0.001 compared with BSR.
flow may be reduced. This results in a decrease in maximal
flow across the stenosis and an increase in distal pressure,
which may result in a negative FFR even in the presence of
a functionally significant stenosis.8,9,32,33 Conversely, a low
microvascular resistance causing a high flow rate through an
epicardial vessel may in the presence of a stenosis give rise
to a positive FFR by increasing the stenosis pressure gradient
although flow through the stenosis is normal.9,33,34 In assessment of CFVR, in addition to its sensitivity to alterations in
microvascular resistance, the absolute value obtained is influenced to a large extent by variations in baseline and maximal flow velocity, which can be caused by factors not related
to stenosis severity.8 Furthermore, assessment of an optimal
flow velocity signal, necessary for an objective CFVR value,
is more difficult than pressure measurements. Both FFR and
CFVR therefore have their ambiguities when representing
the only physiological parameter assessed. Although previously assumed that the combination of FFR and CFVR would
improve diagnostic and prognostic value,32 it has already been
shown that discordance between FFR and CFVR is present in
27% of cases,9 hampering clinical decision-making.
Indices of Stenosis Resistance
The advantage of either index of stenosis resistance is inherited by the simultaneous use of both pressure and flow velocity
information, which results in the ability to assess the relative
influence of microvascular and stenosis resistances (SRs).
Although the previously introduced HSR11 also depends on
the presence of maximal hyperemia, the pressure drop across
the stenosis and flow velocity are affected similarly when the
hyperemic state is suboptimal. Therefore, the effect of submaximal hyperemic flow on HSR is rather limited. Obviously,
the major advantage of BSR is that it does not require a hyperemic state at all.
Overall, the assessment of indices of SR inherits the same
technical difficulties accompanying Doppler flow velocity measurements in the assessment of CFVR. Importantly,
because of the low pressure gradient and flow velocity during
baseline conditions, small errors in pressure and flow velocity
measurements may result in relatively large errors in stenosis
resistance values, and therefore the use of a hyperemic agent
is expected to result in an improvement of diagnostic accuracy, as is supported by the findings in the present study.
False-Positive and False-Negative Results
False-positive or false-negative results for FFR have been
reported to occur in 7%35 to 25% of cases,11,32 and in 8% to
25% of cases11,32 for CFVR. In our study, false-positive or
-negative outcomes for FFR or CFVR were present in 26%
and 29% of cases, respectively (Table 6). Importantly, the
shift in the cutoff value for FFR from 0.75 to 0.80, which is
implemented in recent revascularization guidelines,3 would
have resulted in a significant increase in nonischemic lesions
that receive percutaneous coronary intervention from 16% to
27%, whereas the decrease in ischemic lesions left untreated
is only minor from 10% to 8%. However, the cutoff value
of 0.80 is based on studies assessing the prognostic value
of FFR, which explains the lower diagnostic accuracy.36
Notwithstanding the superior diagnostic accuracy of HSR,
the use of BSR notably results in a similar amount of falsepositive and false-negative outcomes when compared with
both FFR and CFVR and in a significant decrease in the
number of inaccurately treated lesions when compared with
FFR with a cutoff value of 0.80 (P=0.001).
Study Limitations
Whereas developments in wire technology have resulted in
the availability of a double sensor-equipped guidewire,37 pressure and flow velocity measurements were performed subsequently with separate sensor-equipped guidewires in the
present study, which could inherit a bias due to a possible
location shift between simultaneous measurement. Although
the technique for simultaneous measurement of coronary
pressure and flow velocity is readily available, the technique
is currently only minimally adopted in daily clinical practice
due to the perception of clinical cardiologists and industrial
partners that coronary pressure alone is sufficient for diagnostic purposes in daily coronary interventional practice. Because
there is an important underdevelopment in comparison with
systems measuring only intracoronary pressure, assessment
of optimal intracoronary hemodynamic signals is dependent
on operator experience with this specific armamentarium, and
universal adoption will depend on currently ongoing technical
improvements that are expected to improve the feasibility of
simultaneous measurements of coronary pressure and flow in
the near future.
Furthermore, as mentioned previously, there still exists
debate regarding the magnitude of the adenosine dose to
be used to induce maximal hyperemia. The dosage used in
this study (20 μg for the right coronary artery and 40 μg for
the left coronary artery) is, however, considered adequate
to induce maximal hyperemia.14,15,20 Importantly, an insufficient amount of adenosine induces limited maximal flow, but
stenosis pressure drop and flow velocity are affected in the
same direction, limiting the effect of insufficient hyperemia
on HSR.
van de Hoef et al Adenosine-Free Functional Lesion Severity 513
Additionally, it is important to note that the cutoff value for
BSR was derived from the current data set, which provides
some advantage over the other parameters for which we used
prespecified cutoff values. However, the best cutoff values
derived from this data set would have been 0.76 for FFR, 1.80
for CFVR, and 0.81 mm Hg · cm−1 · sec for HSR. The use
of data-derived cutoff values would therefore not have influenced the conclusions of the present article.
Finally, the use of MPS as a gold standard for detection
of myocardial ischemia has its limitations, because MPS is
known to be limited in detecting true ischemia, especially
in patients with multivessel disease or previous myocardial
infarction, as were included in this study.
Conclusion
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The use of a parameter based on both intracoronary pressure
and blood flow velocity measurements during baseline conditions, BSR, has an equal diagnostic accuracy for reversible
perfusion defects on MPS as compared with the most frequently used method for coronary stenosis severity evaluation, FFR. When the use of hyperemic agents is cumbersome,
BSR may therefore provide a novel tool for vasodilator-free
functional stenosis severity assessment. Further prospective
studies are however needed to confirm these findings in the
setting of contemporary physiologically guided percutaneous
coronary intervention.
Acknowledgments
We acknowledge the nursing staff of the cardiac catheterization laboratory (Head: MGH Meesterman) for their skilled assistance.
Sources of Funding
This study was funded in part by the European Community’s Seventh
Framework Programme (FP7/2007-2013) under grant agreement
no. 224495 (euHeart project) and by grants from the Dutch Heart
Foundation (2006B186, 2000.090, and D96.020)).
Disclosures
None.
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Diagnostic Accuracy of Combined Intracoronary Pressure and Flow Velocity Information
During Baseline Conditions: Adenosine-Free Assessment of Functional Coronary Lesion
Severity
Tim P. van de Hoef, Froukje Nolte, Peter Damman, Ronak Delewi, Matthijs Bax, Steven A.J.
Chamuleau, Michiel Voskuil, Maria Siebes, Jan G.P. Tijssen, Jos A.E. Spaan, Jan J. Piek and
Martijn Meuwissen
Circ Cardiovasc Interv. 2012;5:508-514; originally published online July 10, 2012;
doi: 10.1161/CIRCINTERVENTIONS.111.965707
Circulation: Cardiovascular Interventions is published by the American Heart Association, 7272 Greenville
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Correction
In the article by van de Hoef et al, “Diagnostic Accuracy of Combined Intracoronary Pressure and
Flow Velocity Information During Baseline Conditions: Adenosine-Free Assessment of Functional
Coronary Lesion Severity,” which published online July 10, 2012, and appeared in the August 2012
issue of the journal (Circ Cardiovasc Interv. 2012;5:508–514), a correction was needed.
The authors discovered an inadvertent error in the baseline patient characteristics described in
Table 2 and the corresponding text.
The final version of Table 2 and the corresponding text have been corrected in the online version
of the article.
The authors regret this error.
(Circ Cardiovasc Interv. 2014;7:274.)
© 2014 American Heart Association, Inc.
Circ Cardiovasc Interv is available at http://circinterventions.ahajournals.org
274
DOI: 10.1161/HCV.0000000000000007
Page 147
Résumés d’articles
147
Comparaison entre intervention coronaire percutanée et traitement
médical optimal dans la maladie coronaire stable
Revue systématique et méta-analyse des essais cliniques randomisés
Seema Pursnani, MD, MPH ; Frederick Korley, MD ; Ravindra Gopaul, MBA, MPH ;
Pushkar Kanade, MBBS, MPH ; Newry Chandra, MBBS, MPH ;
Richard E. Shaw, PhD, MA ; Sripal Bangalore, MD, MHA
Contexte—L’intérêt d’une intervention coronaire percutanée (ICP) dans la prise en charge des coronaropathies stables demeure
controversé. Compte tenu des progrès accomplis dans les traitements médicaux et l’arrivée des stents au cours des dix dernières
années, nous avons voulu savoir si le fait de pratiquer une ICP en complément du traitement médical contribuait ou non
à améliorer le pronostic comparativement au traitement médical institué isolément.
Méthodes et résultats—En interrogeant les bases de données PubMed, EMBASE et CENTRAL, nous avons effectué une revue
systématique et une méta-analyse des essais cliniques randomisés publiés jusqu’en janvier 2012 et qui avaient comparé la
revascularisation par ICP au traitement médical optimal (TMO) chez des patients coronariens stables. Le critère de jugement
principal a été la mortalité liée à une quelconque cause tandis que les critères de jugement secondaires comprenaient le décès de
cause cardiovasculaire, l’infarctus du myocarde non fatal, la réalisation d’une nouvelle revascularisation et l’absence d’angor.
Les analyses principales ont porté sur la plus longue durée de suivi disponible et les analyses secondaires ont été stratifiées en
fonction de la durée des essais en distinguant suivis à court terme (n’ayant pas excédé 1 an), de durée intermédiaire (1 à 5 ans) et
de longue durée (5 ans ou plus). Nous avons identifié 12 essais cliniques randomisés ayant porté sur un total de 7 182 patients
qui satisfaisaient à nos critères de sélection. Les analyses principales ont montré que, comparativement au TMO, la réalisation
d’une ICP n’avait pas significativement amélioré la mortalité globale (risque relatif [RR] : 0,85 ; intervalle de confiance [IC] à
95 % : 0,71–1,01) ni les taux de décès de cause cardiaque (RR : 0,71 ; IC à 95 % : 0,47–1,06), d’infarctus du myocarde non fatals
(RR : 0,93 ; IC à 95 % : 0,70–1,24) et de nouvelles revascularisations (RR : 0,93 ; IC à 95 % : 0,76–1,14), les résultats ayant été
similaires quelle qu’ait été la durée de suivi. L’analyse de sensibilité réalisée en retenant uniquement les essais dans lesquels
l’utilisation de stents avait dépassé 50 % a objectivé un amoindrissement de la taille de l’effet exercé par l’ICP sur la mortalité
liée à toute cause (RR : 0,93 ; IC à 95 % : 0,78–1,11). En revanche, s’agissant de l’absence d’angor, la réalisation d’une ICP a
significativement amélioré le pronostic comparativement au TMO (RR : 1,20 ; IC à 95 % : 1,06–1,37) et ce, à tous les temps
d’évaluation.
Conclusions—Cette analyse exhaustive et extrêmement rigoureuse des essais menés chez des patients atteints de maladie coronaire
stable a montré que, comparativement au TMO, la réalisation d’une ICP n’avait pas diminué les risques de mortalité, de décès
de cause cardiovasculaire, d’infarctus du myocarde non fatal ou de nouvelle revascularisation. L’ICP ayant toutefois plus
fortement amélioré les symptômes angineux que le TMO instauré seul, des études plus vastes et offrant davantage de puissance
sont nécessaires pour confirmer cette observation. (Traduit de l’anglais : Percutaneous Coronary Intervention Versus
Optimal Medical Therapy in Stable Coronary Artery Disease; A Systematic Review and Meta-Analysis of Randomized Clinical
Trials. Circ Cardiovasc Interv. 2012;5:476–490.)
Mots clés : angor 䊏 maladie coronaire 䊏 traitement médical optimal 䊏 intervention coronaire percutanée
Valeur diagnostique des mesures combinées de la pression
intracoronaire et de la vitesse du flux sanguin en conditions basales
Evaluation de la sévérité des lésions fonctionnelles coronaires
sans recours à l’adénosine
Tim P. van de Hoef, MD ; Froukje Nolte, MSc ; Peter Damman, MD ; Ronak Delewi, MD ;
Matthijs Box, MD ; Steven A.J. Chamuleau, MD, PhD ; Michiel Voskuil, MD, PhD ; Maria Siebes, PhD ;
Jan G.P. Tijssen, PhD ; Jos A.E. Spaan, PhD ; Jan J. Piek, MD, PhD ; Martijn Meuwissen, MD, PhD
Contexte—L’appréciation de la sévérité des lésions fonctionnelles coronaires à partir des paramètres physiologiques intracoronaires tels que la réserve de vitesse du flux coronaire et la fraction de flux de réserve, d’utilisation plus courante, est
hautement conditionnée par l’induction d’une hypérémie maximale. Nous avons évalué la valeur diagnostique de l’indice
de résistance sténotique en l’absence d’hypérémie, c’est-à-dire dans les conditions basales, comparativement aux paramètres
hémodynamiques intracoronaires ordinairement mesurés en phase hypérémique, car l’obtention d’une telle hypérémie peut être
malaisée en pratique clinique courante.
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148
Circulation
Mars 2013
Méthodes et résultats—Des scintigraphies de perfusion myocardique ont été pratiquées chez 232 patients qui totalisaient 299
lésions (diamètre moyen des sténoses : 55 ± 11 %), afin de documenter les défauts de perfusion réversibles. La pression
intracoronaire et la vitesse du flux sanguin en aval des sténoses ont été mesurées à l’aide de sondes munies d’un capteur à l’état
basal et en situation d’hyperémie maximale, induite par l’administration intracoronaire d’un bolus d’adénosine (20–40 µg).
Nous avons estimé les résistances sténotiques (RS) en conditions basales et en phase d’hypérémie ainsi que la fraction de réserve
du flux et la réserve de vitesse du flux coronaire. En nous appuyant sur les courbes de caractéristiques opérationnelles de
réception, nous avons comparé les valeurs de chacun des paramètres qui étaient indicatives d’une ischémie myocardique sur
la scintigraphie de perfusion myocardique. La RS basale a fait preuve d’un bon niveau de concordance avec les données de la
scintigraphie de perfusion myocardique. Le degré de performance diagnostique de la RS mesurée à l’état basal (aire sous
la courbe : 0,77 ; IC à 95 % : 0,71–0,83) a été comparable à ceux de la fraction de flux de réserve et de la réserve de vitesse du flux
coronaire (aires sous la courbe respectives : 0,77 [IC à 95 % : 0,71–0,83] et 0,75 [IC à 95 % : 0,68–0,81] ; p >0,05 comparativement à la RS basale pour les deux paramètres). En revanche, la RS en situation hypérémique, établie en combinant les mesures
de la pression intracoronaire et de la vitesse du flux lors d’une hypérémie, s’est révélée supérieure à tous les autres paramètres
(aire sous la courbe : 0,81 ; IC à 95 % : 0,76–0,87 ; p <0,05 comparativement aux autres paramètres).
Conclusions—La mesure combinée de la pression intracoronaire et de la vitesse du flux en conditions basales peut permettre
l’évaluation de la sévérité des lésions fonctionnelles sans qu’il soit besoin de recourir à un puissant vasodilatateur. (Traduit de
l’anglais : Diagnostic Accuracy of Combined Intracoronary Pressure and Flow Velocity Information During Baseline Conditions:
Adenosine-Free Assessment of Functional Coronary Lesion Severity. Circ Cardiovasc Interv. 2012;5:508–514.)
Mots clés : maladie coronaire 䊏 réserve coronaire 䊏 fraction de flux de réserve 䊏 hémodynamique 䊏 physiologie
L’index de résistance microcirculatoire est prédictif du risque
d’infarctus du myocarde secondaire à une intervention
coronaire percutanée
Martin K.C. Ng, MBBS, PhD ; Andy S.C. Yong, MBBS, PhD ; Michael Ho, MD ; Maulik G. Shah, MD ;
Chirapan Chawantanpipat, MBBS ; Rachel O’Connell, MMedStat ; Anthony Keech, MBBS, MClinEpi ;
Leonard Kritharides, MBBS, PhD ; William F. Fearon, MD
Contexte—Un pourcentage non négligeable de patients ayant fait l’objet d’une intervention coronaire percutanée (ICP)
développent un infarctus du myocarde (IDM) périopératoire ayant un impact péjoratif sur le pronostic. A l’heure actuelle,
aucun moyen clinique ne permet de prédire l’éventuelle survenue d’un tel événement en salle de cathétérisme cardiaque. Nous
avons formé l’hypothèse que l’existence initiale d’une altération de la réserve microcirculatoire coronaire, ayant pour effet de
diminuer la tolérance du patient à l’égard des agressions ischémiques, était susceptible de favoriser la survenue d’un IDM
périopératoire et que celle-ci pouvait être anticipée en mesurant l’index de résistance microcirculatoire (IRm) pendant la
réalisation de l’ICP.
Méthodes et résultats—L’étude a porté sur des patients consécutifs chez lesquels une lésion unique siégeant sur l’artère
interventriculaire antérieure avait été traitée par ICP réglée. Une sonde munie d’un capteur de pression et de température a été
employée pour mesurer l’IRm préalablement à l’intervention. Sur les 50 patients étudiés, 10 ont présenté un IDM périopératoire. Les analyses par régression logistique binaire effectuées sur l’ensemble des paramètres cliniques, opératoires
et physiologiques ont révélé que les facteurs univariés prédictifs de la survenue d’un IDM périopératoire étaient l’IRm préopératoire (p = 0,003) et le nombre de stents utilisés (p = 0,039). L’IRm préopératoire a été le seul facteur prédictif indépendant
mis en évidence par les analyses par régression bivariée pratiquées en ajustant les données en fonction de chaque covariable
disponible une par une (p ≤0,02 pour toutes les analyses). L’existence d’un IRm préopératoire égal ou supérieur à 27 U a été
prédictif de la survenue d’un IDM périopératoire avec une sensibilité de 80,0 % et une spécificité de 85,0 % (statistique C : 0,80 ;
p = 0,003). Elle est, de fait, apparue comme un facteur indépendant à l’origine d’un risque 23 fois supérieur de survenue d’un
IDM périopératoire (odds ratio : 22,7 ; IC à 95 % : 3,8–133,9).
Conclusions—Ces données portent à penser que l’état de la microcirculation coronaire joue un rôle déterminant dans la propension
à développer un IDM périopératoire à l’occasion d’une ICP programmée. La mesure de l’IRm peut être mise à profit pour
anticiper le risque de nécrose myocardique et pour décider des stratégies préventives adjuvantes. (Traduit de l’anglais : The Index
of Microcirculatory Resistance Predicts Myocardial Infarction Related to Percutaneous Coronary Intervention. Circ Cardiovasc
Interv. 2012;5:515–522.)
Mots clés : angioplastie 䊏 microvaisseaux 䊏 microcirculation 䊏 infarctus du myocarde
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