(Circulation. 2000;101:1344.)
© 2000 American Heart Association, Inc.
From Bench to Bedside |
Coronary Physiology Revisited
Practical Insights From the Cardiac Catheterization Laboratory
From the Department of Internal Medicine, Division of Cardiology, Saint Louis University Health Sciences Center, St. Louis, Mo.
Correspondence to Morton J. Kern, MD, Director, J.G. Mudd Cardiac Catheterization Laboratory, Saint Louis University Health Sciences Center, 3635 Vista Avenue at Grand Blvd, St. Louis, MO 63110. E-mail kernm{at}slu.edu
Abstract
Abstract—Various coronary physiological measurements can be made in the cardiac catheterization laboratory using sensor-tipped guidewires; they include the measurement of poststenotic absolute coronary flow reserve, the relative coronary flow reserve, and the pressure-derived fractional flow reserve of the myocardium. Ambiguity regarding abnormal microcirculation has been reduced or eliminated with measurements of relative coronary flow reserve and fractional flow reserve. The role of microvascular flow impairment can be separately determined with coronary flow velocity reserve measurements. In addition to lesion assessment before and after intervention, emerging applications of coronary physiology include the determination of physiological responses to new pharmacological agents, such as glycoprotein IIb/IIIa blockers, in patients with acute myocardial infarction. Measurements of coronary physiology in the catheterization laboratory provide objective data that complement angiography for clinical decision-making.
Key Words: physiology • catheterization • heart • coronary blood flow
An appreciation of coronary physiology is an integral part of clinical decision-making for cardiologists treating patients with coronary artery disease. The pioneering research efforts of Dr Lance Gould, who explored the relationship between the anatomic severity of a stenosis and its flow resistance,1 2 have been transferred to clinical practice.3 4 Within the last few years, technology has advanced such that, in patients undergoing coronary angiography, the influence of a coronary stenosis on the distal arterial pressure-flow relationship can now be easily and safely determined with sensor-tipped angioplasty guidewires that measure the poststenotic absolute coronary flow velocity reserve (CVR), the relative CVR (rCVR), and the pressure-derived fractional flow reserve of the myocardium (FFR). However, theoretical concerns regarding the translation of basic physiology from experimental animal models has given some clinicians pause in applying the available techniques for patient care.5 6 This review will discuss the current concepts, methods, and clinical outcomes of these techniques and provide practical insights for patient management.
Before applying these physiological measurements, a brief review of several fundamental principles is in order. Recall that when an epicardial stenosis produces an increased resistance to flow, the distant microvascular resistance vessels dilate to maintain regional basal flow at a level appropriate for concurrent myocardial oxygen demand. The increased dilation reduces the potential maximal flow reserve available. Because the distal microcirculation has compensated for the potential reduction in regional flow, the resting poststenotic epicardial conduit blood flow, depending on the severity of the stenosis, may be somewhat diminished; however, this epicardial flow usually satisfactorily maintains myocardial function and metabolism. Under these conditions, any increase in myocardial oxygen demand or other hyperemic stimuli now results in a smaller increment in poststenotic flow relative to the coronary flow increase that would be elicited in the same (or another) myocardial region without a stenosis (ie, diminished CVR and rCVR).
A significant stenosis also produces distal artery pressure
loss (ie, a translesional pressure gradient) because of a loss of
kinetic (flow) energy to viscous friction, turbulence, and flow
separation. The reduction of the distal distending arterial
pressure results in a pressure differential or gradient between the
driving aortic pressure and the poststenotic coronary
pressure. The degree of pressure loss is directly related to the flow
rate as described by the curvilinear pressure-flow relationship of the
particular lesion resistance (Figure 1
).1 2
|
P) vs coronary flow. Bottom, Absolute distal
coronary pressure (Pd) versus flow. Increasing flow
produces marked loss of Pd and an increase in Beyond Coronary Pressure Gradients
For clinical coronary artery lesion assessment, resting pressure gradients measured during the early experience with coronary angioplasty were unsatisfactory because of (1) in-adequate devices (ie, balloon catheters), (2) data being used in an incompletely understood manner (ie, only at rest and not during maximal blood flow),7 8 and (3) a weak correlation to ischemic testing and clinical outcomes.7 9 10 Pijls et al11 12 13 demonstrated that the hyperemic absolute distal coronary pressure, but not the resting pressure gradient, is related to the ischemic potential of a stenosis. Moreover, they derived a new concept of a pressure-derived estimate of coronary blood flow, the FFR. The FFR is the fraction of maximal coronary blood flow that goes through the stenotic vessel, expressed as a percentage of blood flow through the same artery in the theoretical absence of the stenosis. The FFR, calculated as the ratio of the absolute distal coronary and aortic pressures measured during maximal hyperemia (ie, when minimal resistance is present across both the epicardial and microvascular beds), reflects myocardial perfusion (both antegrade and collateral) rather than merely trans-stenotic pressure loss. Unlike CVR, FFR is independent of driving pressure, heart rate, systemic blood pressure, and the status of the microcirculation,14 and it reflects both antegrade and collateral blood flow. The normal value for FFR is 1 for each patient, coronary artery, myocardial distribution, and microcirculatory status.
Lesion-Specific Physiological Measurements
A normal absolute CVR, the ratio of hyperemic to basal mean flow (velocity), indicates a normal 2-component system, with a patent epicardial conduit supplying a normal myocardial bed. In the absence of epicardial conduit obstruction, the CVR may be abnormal when the microvascular circulation is compromised by left ventricular hypertrophy, chronic or acute ischemia, diabetes mellitus, or other diseased rheological conditions.15 16 An abnormal CVR cannot differentiate which of the 2 components is responsible for flow impairment. In this setting, an additional measurement of CVR in an adjacent, normal vessel as a reference value (CVRreference) can confirm the significance of the coronary lesion and compute the rCVR (rCVR=CVRtarget/CVRreference).17 Assuming that systemic hemodynamic and microcirculatory abnormalities affect the different regions of the myocardium to the same degree, the rCVR should nullify the influence of the variables and provide an enhanced discrimination of flow impairment due to a stenosis.17 The CVR in angiographically normal vessels from adult patients with coronary artery disease risk factors is 2.7±0.618 and, in most studies, it seems to have little regional variation (<15%) in both cardiac transplant patients and patients with chest pain syndromes. The normal value of the rCVR is >0.8.18 19
Unlike absolute CVR, both rCVR and the FFR are considered more lesion-specific physiological measurements. Baumgart et al19 compared FFR to both absolute CVR and rCVR in 24 vessels that had stenoses ranging from 40% to 95% (average, 74±15%). Target and reference vessel CVR were 2.1±0.5 and 2.6±0.7, respectively; the rCVR was 0.82±0.13 (range, 0.53 to 1.0), and the FFR was 0.81±0.15 (range, 0.49 to 0.99). FFR and rCVR, but not CVR, showed a strong curvilinear relationship to percent area stenosis (r=0.89 and r=0.79; P<0.0001), with a close linear relationship between FFR and rCVR (r=0.95; P<0.0001) that supported the lesion-specific nature of these 2 measurements.
Limitations of Coronary Flow Reserve
Microcirculatory impairment is the major limitation in assessing a stenosis using absolute CVR; this issue is addressed by rCVR or FFR. In patients in whom the target vessel supplies an area of myocardial infarction, neither CVR nor rCVR can confidently identify flow impairment due solely to a stenosis because the assumption that the microvascular circulation is uniform no longer applies. In patients with 3-vessel coronary disease, no suitable reference vessel may exist, which compromises the use of rCVR. A lesion in these situations may be best assessed by FFR.
Advantages and Limitations of FFR
Although FFR seems to be independent of microvascular responses or changing hemodynamics,14 which is a significant advantage over CVR, the magnitude of the flow increase during maximal vasodilatation still influences FFR.11 12 A limited increase in flow across a stenosis could minimize the true FFR value. However, because the FFR reflects the extent to which the epicardial resistance reduces myocardial perfusion, it can be argued that in the setting of microvascular disease, a normal FFR indicates that the conduit resistance (ie, the stenosis in question) is not a major contributing factor to perfusion impairment and that the enlargement of such a conduit obstruction would not restore normal perfusion. In such diagnostic dilemmas, FFR and Doppler velocimetry are complementary; they describe the physiology of both the epicardial stenosis and the microvascular disease (if present) as potential contributors to inducible myocardial ischemia.
It should be recognized that the normal threshold of FFR (<0.75) for
ischemia was derived from a selected, stable patient population
with single-vessel coronary disease and normal left
ventricular function. The data are limited for patients
with microvascular disease, acute or remote myocardial infarction, and
unstable angina. Caution should be applied in extending the current
physiological criteria to such patients. The
advantages and limitations of the 3 physiological
measurements for patients with coronary artery disease are
summarized in Table 1.
|
Concerns Regarding the Practical Application of Physiological Measurements in Patients
Although the discussed techniques are particularly well suited for both diagnostic and interventional therapy, several investigators have expressed concerns over the potential technical and biological limitations of in-laboratory physiological measurements.5 6 20 Technical or operator-related artifacts, such as variability in Doppler velocity envelopes, pressure signal drift, or malalignment, should be avoided as previously described.11 18 Similarly, the cross-sectional area of a sensor guidewire (0.16 mm2) is negligible relative to all but the most critical stenoses.21
Although a potentially false-negative physiological evaluation could occur in the setting of transient vasoconstriction of a stenotic lesion or the microcirculation, episodic or dynamic ischemia that is not detectable by measurements at the time of investigation can be attenuated or eliminated by concomitant antianginal therapies. Dynamic stenotic resistance with inducible variations may occur both at rest and during maximal hyperemia22 in response to a variety of intrinsic and extrinsic stimuli.22 23 24 A false-negative CVR could also be obtained if the ischemic myocardium was confined to only a small region, such as the subendocardium or papillary muscle. Like any diagnostic modality, the results must be considered in the dynamic course of the clinical presentation.
The pharmacological hyperemic agents used to identify impaired
flow are thought to be equivalent to exercise stress hyperemia.
These agents may be unsatisfactory in rare individuals with increased
susceptibility to myocardial ischemia that is not reflected
solely in the flow-limiting nature of the stenosis. Figure 2 illustrates the
physiological assessment of difficult intermediate
coronary stenoses.
|
Clinical Validation
Although some of the theoretical concerns regarding the limitations of direct physiological measurements cannot be completely satisfied, the clinical validation and outcomes strongly support the practical value of in-laboratory measurements. Many of the above-noted concerns and potential complexities of using coronary physiological measurements for clinical decisions arise from the failure of suitable experimental animal and clinical studies to define unambiguous criteria of myocardial ischemia. In patients, the validation of coronary physiological criteria has been established by population correlations with clinically accepted norms of several types of ischemic stress provocation.13 25 26 27 28 29 30 31 32 33
For poststenotic coronary flow velocity reserve,
several single-center studies26 27 28 and one multicenter
trial29 have reported strong correlations with myocardial
stress perfusion; one study using 2D echocardiographic
stress imaging32 reported correlations with an abnormal
distal CVR<2.0, which corresponded to reversible myocardial perfusion
imaging defects (and stress-induced wall motion). These studies had
high sensitivity (86% to 92%), specificity (89% to 100%),
predictive accuracy (89% to 96%), and positive and negative
predictive values (94% to 100% and 77% to 95%, respectively; Table 2).
|
Similarly, for FFR, Pijls et al13 and De Bruyne et al25 also report high correlations for identifying reversible ischemia with an FFR<0.75. In the study by Pijls et al,13 sensitivity was 88%, specificity was 100%, and positive and negative predictive values were 100% and 88%, respectively; the study had a predictive accuracy of 93%.
The clinical outcomes of deferring coronary intervention for
intermediate stenoses with normal physiology that are now
reported in 
5 studies13 34 35 36 37 38 are remarkably
consistent, with clinical event rates of <10% over a 2-year
follow-up period. In these studies, because of clinical requirements,
it was not feasible to defer treatment in symptomatic
patients with abnormal translesional physiology. It is highly likely
that these individuals would, at the least, continue to be
symptomatic or have higher event rates. It should also be
noted that although the safety of deferring angioplasty on the basis of
a normal CVR can be demonstrated, some patients with deferred
procedures had a lower rate of angina-free follow-up compared with
patients who underwent angioplasty.35 Nonetheless, when
physiologically normal, the functional and
clinical impact of medically-treated, angiographically
intermediately-severe stenoses is associated with an excellent
clinical outcome. Physiological criteria support
decisions to defer intervention in such situations while
continuing medical therapy for endothelial
dysfunction, hypertension, hyperlipidemia, and episodic
coronary vasoconstriction.
Comparison With Intravascular Ultrasound Imaging
Despite sophisticated quantitative modeling, neither intravascular ultrasound imaging (IVUS) nor coronary angiography can predict the resistance to flow through intermediately-narrowed epicardial coronary conduits. This is due to factors such as stenosis length, entrance and exit angles, coefficients of viscous friction and separation, and the status of the distal microvascular bed.
Moses et al39 studied 42 patients with coronary
stenoses ranging from 18% to 95%; they reported that in those
patients with a CVR<1.8, the IVUS reference segment area, IVUS lumen
area, and angiographic percent diameter stenosis were higher
(17.7±0.3 versus 12.9±4.4 mm2,
P<0.05; 6.2±3.76 versus 4.34±2.0
mm2, P<0.05; and 60±14 versus
46±17%, P<0.01, respectively) compared with patients with
a CVR1.8. However, the IVUS minimal luminal diameter and
angiographic percent stenosis were only weakly correlated with
poststenotic CVR (r=0.312, P=0.047; and
r=0.305, P=0.052, respectively). In contrast,
Abizaid et al40 found that before intervention, the
CVR and IVUS minimal luminal cross-sectional areas were correlated
(r=0.83, P<0.0001); after the procedure,
this relationship was attenuated (r=0.514,
P=0.006; and, after stent placement, r=0.62,
P=0.031). An IVUS minimal lumen cross-sectional area
4 mm2 had a diagnostic
accuracy of 89% for a CVR 2.0. Recently, Takagi et
al41 demonstrated that an IVUS minimal lumen area
<3.0 mm2 and an area stenosis
<60% had 100% predictive accuracy for a FFR<0.75. Despite a precise
dimensional measurement, a single tomographic IVUS image (except in the
extremes) correlated weakly with measured coronary
physiological responses.
Conversely, FFR may be equivalent to IVUS in the assessment of optimal stent deployment. Hanekamp et al42 found IVUS and FFR>0.94 had 91% concordance in the identification of optimal stent apposition and deployment.
Physiological End Points for Coronary Interventions
It is now known that the failure of coronary blood flow
reserve to improve after balloon angioplasty in 50% of
patients43 44 is principally due to 2 mechanisms:
impairment of microcirculatory responses (either preexisting or induced
after vessel trauma) and/or inadequate epicardial lumen expansion not
readily appreciated by angiography. Microvascular circulatory
impairment, which was initially thought to be the predominant
mechanism, is likely the less common condition because stenting,
compared with angioplasty alone, achieves a larger and more uniformly
cylindrical lumen by IVUS and normalizes CVR in most (
80%)
patients.45 In the 20% of patients with a poststent
CVR<2.0, rCVR or FFR may be useful in identifying persistent conduit
abnormalities. A typical example of pressure and flow measurements
after coronary angioplasty and stenting is illustrated in
Figure 3.
|
A physiological end point associated with improved
late outcomes after coronary angioplasty was identified in the
Doppler End point Balloon Angioplasty Trial, Europe (DEBATE I),
trial.46 A CVR>2.5 coupled with an acceptable
quantitative coronary angiographic result (<35% diameter
stenosis) identified a subset of patients after single-vessel
balloon angioplasty in whom there was a 16% angiographic
restenosis rate and a 16% target lesion
revascularization rate at the 6-month follow-up.
Using FFR after angioplasty without stenting, Bech et al47
found that when a FFR>0.9 was achieved, repeat interventions at 6, 12,
and 24 months were 12%, 12%, and 15%, respectively, compared with
patients who had a FFR
0.9 after angioplasty, with
restenosis rates of 24%, 28%, and 30% at 2 years.
A physiologically-guided angioplasty approach is being prospectively evaluated in 3 multicenter trials: DESTINI-CFR (Doppler Endpoint Stent International Investigation of Coronary Flow Reserve), DEBATE II, and FROST (French Optimal Stent Trial. These studies will confirm whether a provisional, physiologically-guided approach will produce clinical outcomes equivalent to a mandatory or primary stent approach without the adverse effects of stenting.
Preliminary data from studies in >1000 patients indicate that although
crossover to stenting was required in 40% to 50% of patients, the
major adverse in-hospital and 6-month clinical cardiac event rates were
similar in both provisional and primary stent strategies. The
physiologically-guided approach to balloon
angioplasty, although clinically supported and economically attractive,
seems limited by operator preferences and advances in stent technology
that have reduced stent-related complications and
restenosis.
Emerging Developments in Catheterization Laboratory-Based Coronary Physiology
The coronary physiology after acute myocardial infarction and reperfusion strongly influences clinical outcomes.48 In patients with acute infarction, the microcirculatory responses to pharmacological and mechanical interventions that release or remove thrombus or particulate matter can be quantitated in physiological terms and, using FFR, discriminated from epicardial flow impairment.
For example, Claeys et al49 reported that for similar angiographic stenoses, the CVR measured 13±7 days after acute myocardial infarction in 36 patients was lower both before and after angioplasty compared with the 38 patients without myocardial infarctions (1.22±0.26 versus 1.50±0.45 and 1.72±0.43 versus 2.21±0.74, respectively). Although CVR increased after angioplasty in both patient groups, a persistently impaired CVR was present in 80% of patients with acute myocardial infarctions and in only 44% of patients without myocardial infarctions, which suggests that CVR was related more to conduit narrowing than myocardial viability and that increasing the residual lumen by stenting may improve myocardial recovery.
Similarly, Neumann et al50 examined acute and 14-day coronary flow and left ventricular wall motion in 102 patients with acute myocardial infarction who received abciximab and in 98 patients who received standard care with heparin. With similar degrees of residual stenosis, the change in peak (but not resting) flow velocity was greater (P<0.024) and wall motion index improved more (P<0.007) in the patients receiving abciximab. Coronary physiological responses correlated with left ventricular functional recovery, which suggests that mechanisms involving microvascular perfusion may identify new therapeutic avenues in these patients.
Summary
Recent advances in our understanding of human coronary
circulation and clinically-validated physiological
relationships to ischemic stress testing in patients have
enhanced the conceptual applications of and overcome most technical
limitations surrounding the usefulness of in-laboratory
coronary physiological measurements to
facilitate clinical decisions to treat or defer intervention. Although
current clinical practice favors primary stenting, when considering
strategies for optimal balloon angioplasty compared with obligatory
stenting, multicenter preliminary reports indicate that a
physiologically-guided approach can
identify 50% of patients who will have equivalent clinical outcomes
without the additional cost of stents and the potential for in-stent
restenosis.
The practical application of physiological concepts in patients strongly complements coronary lumenology51 and has important clinical and economic implications for the care of patients with coronary artery disease.
Acknowledgments
The author thanks the J.G. Mudd Cardiac Catheterization Laboratory team and Donna Sander for help with manuscript preparation.
References
1. 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]
2. Gould KL, Lipscomb K, Hamilton GW. Physiology 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]
3. White CW, Wright CB, Doty DB, Hiratza LF, Eastham CL, Harrison DG, Marcus ML. Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis? N Engl J Med.. 1984;310:819–824.[Abstract]
4. Kern MJ, De Bruyne B, Pijls NHJ. From research to clinical practice: current role of physiologically based decision making in the catheterization laboratory. J Am Coll Cardiol. 1997;30:613–620.[Abstract]
5.
Klocke FJ. Measurement of coronary flow
reserve: defining pathophysiology versus making decisions about patient
care. Circulation. 1987;76:1183–1189.
6.
Bache RJ. Vasodilator reserve: a functional assessment
of coronary health. Circulation. 1998;98:1257–1260.
7. MacIsaac HC, Knudtson ML, Robinson VJ, Manyari DE. Is the residual translesional pressure gradient useful to predict regional myocardial perfusion after percutaneous transluminal coronary angioplasty? Am Heart J.. 1989;117:783–790.[Medline] [Order article via Infotrieve]
8.
Hodgson JM, Reinert S, Most AS, Williams DO.
Prediction of long-term clinical outcome with final translesional
pressure gradient during coronary angioplasty.
Circulation. 1986;74:563–566.
9. Peterson RJ, King SB III, Fajman WA, Douglas JS Jr, Gruntzig AR, Orias DW, Jones RH. Relation of coronary artery stenosis and pressure gradient to exercise-induced ischemia before and after coronary angioplasty. J Am Coll Cardiol. 1987;10:253–260.[Abstract]
10.
Wijns W, Serruys PW, Reiber JH, van den Brand M,
Simoons ML, Kooijman CJ, Balakumaran K, Hugenholtz PG. Quantitative
angiography of the left anterior descending coronary artery:
correlations with pressure gradient and results of exercise thallium
scintigraphy. Circulation. 1985;71:273–279.
11. Pijls NH, van Son JA, 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;86:1354–1367.
12.
Pijls NH, Van Gelder B, Van der Voort P, Peels K.
Bracke FA, Bonnier HJ, El Gamal MI. Fractional flow reserve: a useful
index to evaluate the influence of an epicardial coronary
stenosis on myocardial blood flow. Circulation. 1995;92:3183–3193.
13.
Pijls NHJ, De Bruyne B, Peels K, Van der Voort P,
Bonnier HJRM, Bartunek J, Koolen JJ. Measurement of myocardial
fractional flow reserve to assess the functional severity of
coronary artery stenosis. N Engl J
Med. 1996;334:1703–1708.
14.
De Bruyne B, Bartunek J, Sys SU, Pijls NHJ, Heyndrickx
GR, Wijns W. Simultaneous coronary pressure and
flow velocity measurements in humans: feasibility, reproducibility, and
hemodynamic dependence of coronary flow
velocity reserve, hyperemic flow versus pressure slope index,
and fractional flow reserve. Circulation. 1996;94:1842–1849.
15. Strauer BE. The significance of coronary reserve in clinical heart disease. J Am Coll Cardiol. 1990;15:775–783.[Abstract]
16. Brush JE Jr, Canon RO III, Schenke WH, Bonow RO, Leon MB, Maron BJ, Epstein SE. Angina due to coronary microvascular disease in hypertensive patients without left ventricular hypertrophy. N Engl J Med. 1988;319:1302–1307.[Abstract]
17. Gould KL, Kirkeeide R, Buchi M. Coronary flow reserve as a physiologic measure of stenosis severity, part I: relative and absolute coronary flow reserve during changing aortic pressure; part II: determination from arteriographic stenosis dimensions under standardized conditions. J Am Coll Cardiol. 1990;15:459–474.
18. Kern MJ, Bach RG, Mechem CJ, Caracciolo EA, Aguirre FV, Miller LW, Donohue TJ. Variations in normal coronary vasodilatory reserve stratified by artery, gender, heart transplantation, and coronary artery disease. J Am Coll Cardiol. 1996;28:1154–1160.[Abstract]
19.
Baumgart D, Haude M, Goerge G, Ge J, Vetter S, Dagres
N, Heusch G, Erbel R. Improved assessment of coronary
stenosis severity suing the relative flow velocity reserve.
Circulation. 1998;98:40–46.
20. Wilson RF, Laxson DD. Caveat emptor: a clinician’s guide to assessing the physiologic significance of arterial stenoses. Cathet Cardiovasc Diagn. 1993;29:93–98.[Medline] [Order article via Infotrieve]
21. De Bruyne B, Pijls NH, 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 angioplasty guide wire. J Am Coll Cardiol. 1993;22:119–126.[Abstract]
22. Gould KL. Dynamic coronary stenosis. Am J Cardiol. 1980;45:286–292.[Medline] [Order article via Infotrieve]
23. Nabel EG, Selwyn AP, Ganz P. Large arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis. J Am Coll Cardiol. 1990;16:349–356.[Abstract]
24. Santamore WP, Walinsky P. Altered coronary flow responses to vasoactive drugs in the presence of coronary arterial stenosis in the dog. Am J Cardiol. 1980;45:276–285.[Medline] [Order article via Infotrieve]
25.
De Bruyne B, Bartunek J, Sys SU, Heyndrickx GR.
Relation between myocardial fractional flow reserve calculated from
coronary pressure measurements and exercise-induced myocardial
ischemia. Circulation. 1995;92:39–46.
26.
Miller DD, Donohue TJ, Younis LT, Bach RG, Aguirre FV,
Wittry MD, Goodgold HM, Chaitman BR, Kern MJ. Correlation of
pharmacologic 99 mtc-sestamibi myocardial perfusion imaging with
poststenotic coronary flow reserve in patients with
angiographically intermediate coronary artery stenoses.
Circulation. 1994;89:2150–2160.
27. Joye JD, Schulman DS, Lasorda D, Farah T, Donohue BC, Reichek N. Intracoronary Doppler guide wire versus stress single-photon emission computed tomographic thallium-201 imaging in assessment of intermediate coronary stenoses. J Am Coll Cardiol. 1994;24:940–947.[Abstract]
28. Deychak YA, Segal J, Reiner JS, Rohrbeck SC, Thompson MA, Lundergan CF, Ross AM, Wasserman AG. Doppler guide wire flow-velocity indexes measured distal to coronary stenoses associated with reversible thallium perfusion defects. Am Heart J. 1995;129:219–227.[Medline] [Order article via Infotrieve]
29.
Heller LI, Cates C, Popma J, Deckelbaum LI, Joye JD,
Dahlberg ST, Villegas BJ, Arnold A, Kipperman R, Grinstead WC, Balcom
S, Ma Y, Cleman M, Steingart RM, Leppo JA, for the FACTS study group.
Intracoronary Doppler assessment of moderate
coronary artery disease: comparison with
201Tl imaging and coronary angiography.
Circulation. 1997;96:484–490.
30. Donohue TJ, Miller DD, Bach RG, Tron C, Wolford T, Caracciolo EA, Aguirre FV, Younis LT, Chaitman BR, Kern MJ. Correlation of poststenotic hyperemic coronary flow velocity and pressure with abnormal stress myocardial perfusion imaging in coronary artery disease. Am J Cardiol. 1997;77:948–954.
31. Schulman DS, Lasorda D, Farah T, Soukas P, Reichek N, Joye JD. Correlations between coronary flow reserve measured with a Doppler guide wire and treadmill exercise testing. Am Heart J. 1997;134:99–104.[Medline] [Order article via Infotrieve]
32.
Danzi GB, Pirelli S, Mauri L, Testa R, Ciliberto GR,
Massa D, Lotto AA, Campolo L, Parodi O. Which variable of
stenosis severity best describes the significance of an
isolated left anterior descending coronary artery lesion?
Correlation between quantitative coronary angiography,
intracoronary Doppler measurements and high dose
dipyridamole echo-cardiography. J Am Coll
Cardiol. 1998;31:526–533.
33. Bartunek J, Van Schuerbeeck E, De Bruyne B. Comparison of exercise electrocardiography and dobutamine echocardiography with invasively assessed myocardial fractional flow reserve in evaluation of severity of coronary arterial narrowing. Am J Cardiol. 1997;79:478–481.[Medline] [Order article via Infotrieve]
34. Kern MJ, Donohue TJ, Aguirre FV, Bach RG, Caracciolo EA, Wolford T, Mechem CJ, Flynn MS, Chaitman BR. Clinical outcome of deferring angioplasty in patients with normal translesional pressure-flow velocity measurements. J Am Coll Cardiol. 1995;25:178–187.[Abstract]
35. Ferrari M, Schnell B, Werner GS, Figulla HR. Safety of deferring angioplasty in patients with normal coronary flow velocity reserve. J Am Coll Cardiol. 1999;33:83–87.
36.
Bech GJ, De Bruyne B, Bonnier HJRM, Bartunek J, Wijns
W, Peels K, Heyndrickx GR, Koolen JJ, Pijls NHJ. Long-term follow-up
after deferral of percutaneous transluminal
coronary angioplasty of intermediate stenosis on the
basis of coronary pressure measurement. J Am Coll
Cardiol. 1998;31:841–847.
37. Lesser JL, Wilson RF, White CW. Physiologic assessment of coronary stenoses of intermediate severity can facilitate patient selection for coronary angioplasty? Coron Artery Dis. 1990;1:697–705.
38. Gruberg L, Kapeliovich M, Roguin A, Grenadier E, Markiewicz W, Beyar R. Deferring angioplasty in intermediate coronary lesions based on coronary flow criteria is safe: comparison of a deferred group to an intervention group. Int J Cardiovasc Interv. 1999;2:35–40.
39. Moses JW, Undermir C, Strain JE, Kreps EM, Higgins JE, Gleim GW, Kern MJ. Relation between single tomographic intravascular ultrasound image parameters and intracoronary Doppler flow velocity in patients with intermediately severe coronary stenoses. Am Heart J. 1998;135:988–994.[Medline] [Order article via Infotrieve]
40. Abizaid A, Mintz GS, Pichard AD, Kent KM, Satler LF, Walsh CL, Popma JJ, Leon MB. Clinical, intravascular ultrasound, and quantitative angiographic determinants of the coronary flow reserve before and after percutaneous transluminal coronary angioplasty. Am J Cardiol. 1998;82:423–428.[Medline] [Order article via Infotrieve]
41.
Takagi A, Tsurumi Y, Ishii Y, Suzuki K, Kawana M,
Kasanuki H. Clinical potential of intravascular ultrasound for
physiological assessment of coronary
stenosis: relationship between quantitative ultrasound
tomography and pressure-derived fractional flow reserve.
Circulation. 1999;100:250–255.
42.
Hanekamp CEE, Koolen JJ, Pijls NHJ, Michel HR, Bonnier
HJRM. Comparison of quantitative coronary angiography,
intravascular ultrasound, and coronary pressure measurement to
assess optimum stent deployment. Circulation. 1999;99:1015–1021.
43. Kern MJ, Deligonul U, Vandormael M, Labovitz A, Gudipati R, Gabliani G, Bodet J, Shah Y, Kennedy HL. Impaired coronary vasodilatory reserve in the immediate post-coronary angioplasty period: analysis of coronary arterial velocity flow indices and regional cardiac venous efflux. J Am Coll Cardiol. 1989;13:860–872.[Abstract]
44.
Wilson RF, Johnson MR, Marcus ML, Aylward PE, Skorton
DJ, Collins S, White CW. The effect of coronary angioplasty on
coronary flow reserve. Circulation. 1988;77:873–885.
45. Kern MJ, Dupouy P, Drury JH, Aguirre FV, Aptecar E, Bach RG, Caracciolo EA, Donohue TJ, Dubois-Rande J, Geschwind HJ, Mechem CJ, Kane G, Teiger E, Wolford TL. Role of coronary artery lumen enlargement in improving coronary blood flow after balloon angioplasty and stenting: a combined intravascular ultrasound Doppler flow and imaging study. J Am Coll Cardiol. 1997;29:1520–1527.[Abstract]
46.
Serruys PW, di Mario C, Piek J, Schroeder E, Vrints C,
Probst P, De Bruyne B, Hanet C, Fleck E, Haude M, Verna E, Voudris V,
Geschwind H, Emanuelsson H, Muhlberger V, Danzi G, Peels HO, Ford AJ
Jr, Boersma E, for the DEBATE study group. Prognostic value of
intracoronary flow velocity and diameter stenosis in
assessing the short- and long-term outcomes of coronary balloon
angioplasty: the DEBATE study (Doppler Endpoint Balloon Angioplasty
Trial, Europe). Circulation. 1997;96:3369–3377.
47.
Bech GJW, Pijls NHJ, De Bruyne B, Peels K, Michels HR,
Bonnier HJRM, Koolen JJ. Usefulness of fractional flow reserve to
predict clinical outcome after balloon angioplasty.
Circulation. 1999;99:883–888.
48.
Gibson CM, Murphy SA, Rizzo MJ, Ryan KA, Marble SJ,
McCabe CH, Cannon CP, Van de Werf F, Braunwald E, for the
Thrombolysis in Myocardial Infarction (TIMI) study group.
Relationship between TIMI frame count and clinical outcomes after
thrombolytic administration. Circulation. 1999;99:1945–1950.
49. Claeys MJ, Vrints CJ, Bosmans J, Krug B, Blockx PP, Snoeck JP. Coronary flow reserve during coronary angioplasty in patients with recent myocardial infarction: relation to stenosis and myocardial viability. J Am Coll Cardiol. 1996;28:1712–1719.[Abstract]
50.
Neumann F, Blasini R, Schmitt C, Alt E, Dirschinger J,
Gawaz M, Kastrati A, Schomig A. Effect of glycoprotein
IIb/IIIa receptor blockade on recovery of coronary flow and
left ventricular function after the placement of
coronary-artery stents in acute myocardial infarction.
Circulation. 1998;98:2695–2701.
51.
Topol TJ, Nissen SE. Our preoccupation with
coronary luminology: the dissociation between clinical and
angiographic findings in ischemic heart disease.
Circulation. 1995;92:2333–2342.
This article has been cited by other articles:
 |
|
 |
|
  S. M. Bierig, P. Mikolajczak, S. C. Herrmann, N. Elmore, M. Kern, and A. J. Labovitz Comparison of myocardial contrast echocardiography derived myocardial perfusion reserve with invasive determination of coronary flow reserve Eur J Echocardiogr, March 1, 2009; 10(2): 250 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Meimoun, D. Malaquin, T. Benali, J. Boulanger, H. Zemir, and C. Tribouilloy Transient impairment of coronary flow reserve in tako-tsubo cardiomyopathy is related to left ventricular systolic parameters Eur J Echocardiogr, March 1, 2009; 10(2): 265 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Pries, H. Habazettl, G. Ambrosio, P. R. Hansen, J. C. Kaski, V. Schachinger, H. Tillmanns, G. Vassalli, I. Tritto, M. Weis, et al. A review of methods for assessment of coronary microvascular disease in both clinical and experimental settings Cardiovasc Res, November 1, 2008; 80(2): 165 - 174. [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]
|
|
|
|
 |
|
 V. Stangl, V. Witzel, G. Baumann, and K. Stangl Current diagnostic concepts to detect coronary artery disease in women Eur. Heart J., March 2, 2008; 29(6): 707 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. F. Fearon, M. Shah, M. Ng, T. Brinton, A. Wilson, J. A. Tremmel, I. Schnittger, D. P. Lee, R. H. Vagelos, P. J. Fitzgerald, et al. Predictive value of the index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction. J. Am. Coll. Cardiol., February 5, 2008; 51(5): 560 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Melikian, M. T. Kearney, M. R. Thomas, B. De Bruyne, A. M. Shah, and P. A. MacCarthy A simple thermodilution technique to assess coronary endothelium-dependent microvascular function in humans: validation and comparison with coronary flow reserve Eur. Heart J., September 2, 2007; 28(18): 2188 - 2194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Iskandrian Detecting Coronary Artery Disease in Left Bundle Branch Block J. Am. Coll. Cardiol., November 21, 2006; 48(10): 1935 - 1937. [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]
|
|
|
|
|
|
M. K.C. Ng, A. C. Yeung, and W. F. Fearon Invasive Assessment of the Coronary Microcirculation: Superior Reproducibility and Less Hemodynamic Dependence of Index of Microcirculatory Resistance Compared With Coronary Flow Reserve Circulation, May 2, 2006; 113(17): 2054 - 2061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A.E. Spaan, J. J. Piek, J. I.E. Hoffman, and M. Siebes Physiological Basis of Clinically Used Coronary Hemodynamic Indices Circulation, January 24, 2006; 113(3): 446 - 455. [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]
|
|
|
|
 |
|
 N. H J Pijls Optimum guidance of complex PCI by coronary pressure measurement Heart, September 1, 2004; 90(9): 1085 - 1093. [Full Text] [PDF]
|
|
|
|
|
|
S. K. Chugh, J. Koppel, M. Scott, L. Shewchuk, D. Goodhart, R. Bonan, J.-C. Tardif, S. G. Worthley, C. DiMario, M. J. Curtis, et al. Coronary flow velocity reserve does not correlate with TIMI frame count in patients undergoing non-emergency percutaneous coronary intervention J. Am. Coll. Cardiol., August 18, 2004; 44(4): 778 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Parham, A. Bouhasin, J. P. Ciaramita, S. Khoukaz, S. C. Herrmann, and M. J. Kern Coronary Hyperemic Dose Responses of Intracoronary Sodium Nitroprusside Circulation, March 16, 2004; 109(10): 1236 - 1243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Lethen and H. Lambertz Doppler echocardiographic assessment of coronary artery disease: a challenge becomes reality Eur J Echocardiogr, January 1, 2004; 5(1): 5 - 7. [Full Text] [PDF]
|
|
|
|
|
|
W. F. Fearon, H.M. O. Farouque, L. B. Balsam, D. T. Cooke, R. C. Robbins, P. J. Fitzgerald, A. C. Yeung, and P. G. Yock Comparison of Coronary Thermodilution and Doppler Velocity for Assessing Coronary Flow Reserve Circulation, November 4, 2003; 108(18): 2198 - 2200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Lethen, H. P. Tries, S. Kersting, and H. Lambertz Validation of noninvasive assessment of coronary flow velocity reserve in the right coronary artery: A comparison of transthoracic echocardiographic results with intracoronary Doppler flow wire measurements Eur. Heart J., September 1, 2003; 24(17): 1567 - 1575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Werner, P. Bahrmann, O. Mutschke, U. Emig, S. Betge, M. Ferrari, and H. R. Figulla Determinants of target vessel failure in chronic total coronary occlusions after stent implantation: The influence of collateral function and coronary hemodynamics J. Am. Coll. Cardiol., July 16, 2003; 42(2): 219 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Escaned, J. Cortes, A. Flores, J. Goicolea, F. Alfonso, R. Hernandez, A. Fernandez-Ortiz, M. Sabate, C. Banuelos, and C. Macaya Importance of diastolic fractional flow reserve and dobutamine challenge in physiologic assessment of myocardial bridging J. Am. Coll. Cardiol., July 16, 2003; 42(2): 226 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. F. Fearon, L. B. Balsam, H. M. O. Farouque, R. C. Robbins, P. J. Fitzgerald, P. G. Yock, and A. C. Yeung Novel Index for Invasively Assessing the Coronary Microcirculation Circulation, July 1, 2003; 107(25): 3129 - 3132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Stoel, F. Zijlstra, and C. A. Visser Frame Count Reserve Circulation, June 24, 2003; 107(24): 3034 - 3039. [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]
|
|
|
|
|
|
P Garot, O Pascal, M Simon, J L Monin, E Teiger, J Garot, P Gueret, and J L Dubois-Rande Impact of microvascular integrity and local viability on left ventricular remodelling after reperfused acute myocardial infarction Heart, April 1, 2003; 89(4): 393 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Assmus, V. Schachinger, C. Teupe, M. Britten, R. Lehmann, N. Dobert, F. Grunwald, A. Aicher, C. Urbich, H. Martin, et al. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI) Circulation, December 10, 2002; 106(24): 3009 - 3017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Sposito and M. J. Chapman Statin Therapy in Acute Coronary Syndromes: Mechanistic Insight Into Clinical Benefit Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1524 - 1534. [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]
|
|
|
|
|
|
G. S. Werner, M. Ferrari, B. M. Richartz, O. Gastmann, and H. R. Figulla Microvascular Dysfunction in Chronic Total Coronary Occlusions Circulation, September 4, 2001; 104(10): 1129 - 1134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Seabra-Gomes Is there a future for coronary physiological evaluation in clinical decision making? Eur. Heart J., September 2, 2001; 22(18): 1633 - 1635. [PDF]
|
|
|
|
|
|
M. Takeuchi, C. Miyazaki, H. Yoshitani, S. Otani, K. Sakamoto, and J. Yoshikawa Assessment of coronary flow velocity with transthoracic Doppler echocardiography during dobutamine stress echocardiography J. Am. Coll. Cardiol., July 1, 2001; 38(1): 117 - 123. [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]
|
|
|
|
 |
|
 S. E. Langerak, P. Kunz, H. W. Vliegen, J. W. Jukema, A. H. Zwinderman, P. Steendijk, H. J. Lamb, E. E. van der Wall, and A. de Roos MR Flow Mapping in Coronary Artery Bypass Grafts: A Validation Study with Doppler Flow Measurements Radiology, January 1, 2002; 222(1): 127 - 135. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||