CLINICAL STUDY
Fractional flow reserve, absolute and relative coronary blood flow velocity reserve in relation to the results of technetium-99m sestambi single-photon emission computed tomography in patients with two-vessel coronary artery disease
Steven A. J. Chamuleau, MD*,
Martijn Meuwissen, MD*,
Berthe L. F. van Eck-Smit, MD ,
Karel T. Koch, MD*,
Angelina de Jong, MSc*,
Robbert J. de Winter, MD*,
Carl E. Schotborgh, MD*,
Matthijs Bax, MD*,
Hein J. Verberne, MD,
Jan G. P. Tijssen, PhD* and
Jan J. Piek, MD*,1
* Department of Cardiology, Academic Medical Center of Amsterdam, Amsterdam, The Netherlands
Department of Nuclear Medicine, Academic Medical Center of Amsterdam, Amsterdam, The Netherlands
Manuscript received March 9, 2000;
revised manuscript received December 7, 2000,
accepted December 27, 2000.
Reprint requests and correspondence: Dr. J. J. Piek, Department of Cardiology, Room B2-108, Academic Medical Center Amsterdam, Meibergdreef 9, P.O. Box 22660, 1100 DD, Amsterdam, The Netherlands
s.a.chamuleau{at}amc.uva.nl
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Abstract
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OBJECTIVES
We sought to perform a direct comparison between perfusion scintigraphic results and intracoronary-derived hemodynamic variables (fractional flow reserve [FFR]; absolute and relative coronary flow velocity reserve [CFVR and rCFVR, respectively]) in patients with two-vessel disease.
BACKGROUND
There is limited information on the diagnostic accuracy of intracoronary-derived variables (CFVR, FFR and rCFVR) in patients with multivessel disease.
METHODS
Dipyridamole technetium-99m sestambi (MIBI) single-photon emission computed tomography (SPECT) was performed in 127 patients. The presence of reversible perfusion defects in the region of interest was determined. Within one week, angiography was performed; CFVR, rCFVR and FFR were determined in 161 coronary lesions after intracoronary administration of adenosine. The predictive value for the presence of reversible perfusion defects on MIBI SPECT of CFVR, rCFVR and FFR was evaluated by the area under the curve (AUC) of the receiver operating characteristics curves.
RESULTS
The mean percentage diameter stenosis was 57% (range 35% to 85%), as measured by quantitative coronary angiography. Using per-patient analysis, the AUCs for CFVR (0.70 ± 0.052), rCFVR (0.72 ± 0.051) and FFR (0.76 ± 0.050) were not significantly different (p = NS). The percentages of agreement with the results of MIBI SPECT were 76%, 78% and 77% for CFVR, rCFVR and FFR, respectively. Per-lesion analysis, using all 161 measured lesions, yielded similar results.
CONCLUSIONS
The diagnostic accuracy of three intracoronary-derived hemodynamic variables, as compared with the results of perfusion scintigraphy, is similar in patients with two-vessel coronary artery disease. Cut-off values of 2.0 for CFVR, 0.65 for rCFVR and 0.75 for FFR can be used for clinical decision-making in this patient cohort. Discordant results were obtained in 23% of the cases that require prospective evaluation for appropriate patient management.
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Abbreviations and Acronyms
| | AUC | = area under the curve | | CFVR and rCFVR | = coronary flow velocity reserve and relative coronary flow velocity reserve, respectively | | FFR | = fractional flow reserve | | LAD | = left anterior descending coronary artery | | LCx | = left circumflex coronary artery | | MIBI | = technetium-99m labeled sestambi | | RCA | = right coronary artery | | ROC | = receiver operating characteristics | | SPECT | = single-photon emission computed tomography |
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Decisions regarding intracoronary interventions should be based on objective evidence of functional significance of coronary artery narrowings. Therefore, documentation of myocardial ischemia related to the culprit lesion is important for clinical decision-making. Noninvasive diagnostic tests, such as perfusion scintigraphy, are widely applied for evaluation of coronary artery disease. However, perfusion scintigraphy has a limited capability, particularly in multivessel disease, to assign the perfusion defect to a specific epicardial coronary narrowing, especially in the so-called "watershed regions." The introduction of guide wires, equipped with pressure or Doppler sensors, allows selective hemodynamic evaluation of coronary narrowings (1,2). Validation studies of fractional flow reserve (FFR), based on intracoronary pressure measurements, and coronary flow velocity reserve (CFVR), based on intracoronary Doppler flow measurements, demonstrated good agreement with the results of perfusion scintigraphy, both in severely and intermediately narrowed coronary arteries (3–8). These studies were performed predominantly in patients with single-vessel disease. It has been postulated that FFR is a more lesion-specific variable, whereas CFVR is determined by the resistance of both the epicardial coronary narrowing and the distal microvascular bed (9,10). Consequently, it can be anticipated that these intracoronary variables may yield conflicting results. However, a direct comparison of pressure and flow-derived indexes has only been performed in a small cohort of patients with single-vessel disease (11).
The purpose of this study was to compare the predictive value of CFVR, relative coronary flow velocity reserve (rCFVR) and FFR for the detection of reversible defects, as assessed by perfusion scintigraphy, in a large cohort of patients with two-vessel disease.
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Methods
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Study group.
Patients with two-vessel coronary artery disease and stable angina (Canadian Cardiovascular Society [CCS] classes I–III) or unstable angina (Braunwald’s class I or II) were eligible for inclusion in this study. Furthermore, an angiographically normal reference vessel had to be available. A total of 127 patients were prospectively studied. Exclusion criteria included factors precluding dipyridamole infusion and/or assessment of intracoronary measurements (e.g., occlusions, coronary anatomy) and factors influencing coronary hemodynamic variables (e.g., left ventricular hypertrophy, severe valvular heart disease, cardiomyopathy, insulin-dependent diabetes, Q-wave myocardial infarction in the region of interest, previous coronary artery bypass graft surgery of the segment of interest).
Study protocol.
All patients underwent dipyridamole myocardial perfusion scintigraphy within one week before angiography, during which time intracoronary measurements were performed. Patients had two coronary artery narrowings, resulting in a total of 254 lesions. In 59 lesions (23%), intracoronary measurements were not performed per the operator’s interpretation (e.g., technically impossible, total coronary occlusions, lesion location). In 34 severe lesions (13%), it was not possible to measure both flow velocity and pressure. Thus, both flow velocity- and pressure-derived hemodynamic variables were measured in 161 lesions. Angioplasty of the lesions was performed if a reversible defect was present in the area of interest on sestambi single-photon emission computed tomography (SPECT) and if the CFVR, if available, was <2.0.
This study protocol was approved by the Medical Ethics Committee of our institution; all patients gave written, informed consent.
Myocardial perfusion scintigraphy.
Single-photon emission computed tomography was performed using technetium-99m labeled sestambi (MIBI), according to a two-day stress/rest protocol. Dipyridamole (0.56 mg/kg body weight intravenously for 4 min) was used as a hyperemic agent. Antianginal medication was discontinued 48 h before the stress MIBI SPECT study. All patients fasted the day of the MIBI SPECT study. Technetium-99m labeled sestambi (±400 MBq) was injected 4 min after the start of the administration of dipyridamole, as well as the next day for the rest images. Single-photon emission computed tomography was performed using a three-headed gamma camera equipped with low energy, high resolution collimators (Siemens, Hoffman Estate, Illinois), starting 1 h after the administration of MIBI. Acquisition was performed using a 360° noncircular orbit, a 64 x 64 matrix size and an acquisition time of 60 frames of 45 s. Standard filtered back projection was performed without applying attenuation correction. Stress and rest tomographic images were displayed side by side in the short-axis, horizontal long-axis and vertical long-axis reconstruction panel.
A panel of experienced nuclear medicine physicians, who had no knowledge of the angiographic data, evaluated the scintigraphic images. Stress and rest images were semiquantitatively scored as normal or abnormal. Perfusion defects were classified as dubious, mild, moderate or severe. Improvement at rest of more than one grade was considered to be a "reversible" perfusion defect. Improvement of just one grade or no improvement was considered to be a "persistent" perfusion defect. The result was considered "positive" when a reversible defect was allocated to the perfusion territory of the coronary artery of interest. Defects located in the anterior wall and septal region were allocated to the left anterior descending coronary artery (LAD); defects in the lateral wall to the left circumflex coronary artery (LCx); and inferior defects to the right coronary artery (RCA). Apical defects were considered to be located in the LAD region, unless the defect extended to the lateral (LCx) or inferior (RCA) wall. In the watershed regions, the extension of a defect to either the anterior wall (LAD), lateral wall (LCx) or inferior wall (RCA) was decisive for the allocation of a coronary artery to the vascular bed.
Angiography.
All patients were treated with aspirin (100 mg) before the procedure; heparin (5,000 IU) was given as an intravenous bolus at the beginning of the procedure. Coronary angiography, including the intracoronary hemodynamic measurements, was performed according to standard procedure by the percutaneous femoral approach, using a 6F guiding catheter without side holes. Coronary angiography was performed after the administration of an intracoronary bolus of nitroglycerin (0.1 mg) in at least two different, preferably orthogonal, views displaying each index lesion, with minimal foreshortening and no vessel overlap. Coronary lesion severity was measured by quantitative coronary angiography, using the CMS-QCA software, version 3.32 (MEDIS, Leiden, Netherlands), as previously described (12). Percent diameter stenosis was assessed in two views; the most severe one was used in the analysis.
Intracoronary measurements.
At the time of performing the intracoronary measurements, the observer was not aware of the results of the MIBI SPECT study. If possible, intracoronary flow velocity was measured distal to both lesions and also in an angiographically normal coronary artery. Exchanging wires was at the operator’s discretion, to obtain subsequent intracoronary pressure measurements distal to the lesion(s). An intracoronary bolus of 0.1 mg nitroglycerin was administered every 30 min. All measurements were performed at baseline and during hyperemia. Hyperemia was induced by administering an intracoronary bolus of adenosine (15 µg in the RCA and 20 µg in the left coronary artery).
Translesional blood flow velocity was measured with a 0.035-cm (0.014-in.) Doppler guide wire (FloWire, Endosonics, Rancho Cordova, California). The FloWire was advanced distal to the stenosis, avoiding placement adjacent to the side branches. A distance from the stenosis greater than five times the vessel diameter was maintained to avoid post-stenotic turbulent flow and to allow full development of a parabolic flow profile. Distal flow baseline and hyperemic velocity data were obtained, and the Doppler signals were processed by a real-time spectral analyzer, using the Flowmap (Endosonics) (1). The CFVR was computed as the ratio of hyperemic to basal average peak blood flow velocity (13). The CFVR was also obtained in an angiographically normal reference coronary artery. Relative CFVR was defined as the ratio of CFVR of the narrowed vessel to CFVR of the reference coronary artery.
Intracoronary pressure was measured with a 0.035-cm (0.014-in.) pressure guide wire connected to the pressure console (RADI Medical Systems, Uppsala, Sweden). After calibration with the pressure console, the accuracy of the system was verified using the aortic pressure, as measured through the guiding catheter. The wire was advanced with the pressure sensor at least 3 cm distal to the lesion. During maximal hyperemia, FFR was calculated as the ratio of the mean distal to mean aortic pressure.
Data analysis.
Data analysis was performed using the SPSS 10.0.5 software package for Windows (SPSS Inc., 1999, Arlington, Virginia). As 34 of the 127 patients contributed two lesions that were measured with the hemodynamic variables, the intrapatient effects could not be excluded beforehand. Therefore, we performed a per-patient analysis instead of a per-lesion analysis. Of the 34 patients with two lesions, one randomly chosen lesion was used for analysis. Of note, this procedure was repeated eight times to verify consistency. Furthermore, for completeness, the results of the per-lesion analysis were also calculated.
The predictive value for the presence of reversible perfusion defects on MIBI SPECT of CFVR, rCFVR and FFR was evaluated by the area under the curve (AUC) of the receiver operating characteristic curves. A direct comparison between of the AUCs of the three variables was performed by using the software package called ROC Curve Analyzer (written by R. M. Centor and J. Keightley). Accuracy was calculated for predefined and widely used cut-off values, as determined in earlier studies of single-vessel disease (CFVR 2.0, FFR 0.75 and rCFVR 0.65), and for the best cut-off value of the current data set, defined as the highest sum of sensitivity and specificity. Furthermore, the kappa statistic was used to evaluate the cut-off values of the hemodynamic variables as compared with the results of MIBI SPECT. Data are presented as the mean value ± SD, unless indicated otherwise. Linear regression analysis was used to compare CFVR, rCFVR and FFR. Continuous data were compared using the Student t test; binomial data were compared using the chi-square test. A p value <0.05 was considered statistically significant.
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Results
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The baseline characteristics of the 127 study patients were 73% male and mean age 61 years (range 37 to 80). The patients had the following risk factors: 70% with a smoking habit, 33% with hypertension, 58% with hypercholesterolemia, 9% with noninsulin-dependent diabetes and 54% with a positive family history of cardiac disease. Most patients had moderate to severe anginal complaints (2% in CCS I; 18% in CCS II; 59% in CCS III; 21% in Braunwald’s class I or II). The patients used cardiac medications as follows: 79% on beta-blockers, 58% on calcium antagonists, 65% on nitrates, 56% on statins and 19% on angiotensin-converting enzyme inhibitors. The initial hemodynamic data on the total 161 lesions measured and the 127 lesions studied for the per-patient analysis are presented in Table 1. All patients underwent myocardial perfusion scintigraphy within one week before cardiac catheterization. In total, a reversible perfusion defect on MIBI SPECT was found in 52 (32%) of the 161 areas of interest.
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Table 1 Angiographic and Hemodynamic Data on the Total 161 Coronary Lesions (n = 127) and for the Randomly Chosen 127 Lesions for the Per-Patient Analysis
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Using per-patient analysis, the AUC (as measured by ROC analysis) was 0.70 for CFVR, 0.72 for rCFVR and 0.76 for FFR. Direct comparison of the ROC analysis by the AUCs of the hemodynamic variables did not differ significantly (CFVR vs. FFR, p = 0.15; CFVR vs. rCFVR, p = 0.27; FFR vs. rCFVR, p = 0.32). In Table 2, the accuracy is presented for the best cut-off values and the predefined cut-off values for the current data set. There were no significant differences in accuracy, as shown by the 95% confidence intervals. Kappa values indicated moderate agreement at determined the best cut-off value (Table 2). Also, the per-lesion analysis, including all 161 lesions, yielded similar best cut-off values (1.7 for CFVR, 0.60 for rCFVR and 0.74 for FFR) and did not reveal significant differences between the AUCs (0.72 for CFVR, 0.73 for rCFVR and 0.77 for FFR). The accuracy data were similar to those of the per-patient analysis, ranging from 68% to 77%. Plots for the sensitivity and specificity of CFVR, rCFVR and FFR, as calculated with ROC analysis (with the patient as the unit of analysis), are presented in Figure 1, A–C. Linear regression analysis of CFVR versus FFR (y = 0.13x + 0.48; r = 0.53; p < 0.001), CFVR versus rCFVR (y = 0.24x + 0.29; r = 0.62; p < 0.001) and rCFVR versus FFR (y = 0.87x + 0.16; r = 0.55; p < 0.001) yielded similar results.
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Table 2 Per-Patient Analysis (n = 127): Accuracy for CFVR, rCFVR and FFR Versus the Results of Sestambi Single-Photon Emission Computed Tomography, Calculated for Best and Predefined Cut-Off Values
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Figure 1 Plots for the sensitivity and specificity of CFVR (A), relative CFVR (B) and FFR (C), as calculated with receiver operating characteristics analysis on a per-patient basis (n = 127). The best cut-off value (BCV), defined as the highest sum of sensitivity and specificity, is indicated. CFVR = coronary flow velocity reserve; FFR = fractional flow reserve.
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Discussion
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This is the first report of a direct comparison between the results of MIBI SPECT and intracoronary hemodynamic variables in a large cohort of patients (n = 127) with two-vessel coronary artery disease. There were no significant differences in the predictive value of CFVR, rCFVR and FFR using ROC curves for reversible perfusion defects.
Direct comparisons of CFVR, rCFVR and FFR.
The CFVR is determined by the integrity of both the epicardial conduit artery and the distal microvascular bed. Relative CFVR is defined as the ratio of CFVR of the target vessel to CFVR of the angiographically normal reference coronary artery, thus theoretically focusing on the contribution of epicardial narrowing by correcting for microcirculatory disturbances. This concept of rCFVR was introduced by Gould et al. (13) and validated in experimental and clinical studies. The concept of FFR was introduced by Pijls and De Bruyne and colleagues (2,6,9) and was considered to be independent of hemodynamic and microcirculatory confounding factors.
It has been suggested that FFR and rCFVR are more lesion-specific variables than CFVR (8,14,15). However, in the present study (n = 127), we could not demonstrate a better correlation between rCFVR and FFR (r = 0.55) than that between CFVR and FFR (r = 0.53), suggesting that the aforementioned confounding factors influencing CFVR are less pronounced than previously presumed in patients with coronary artery disease. This interpretation also explains why rCFVR did not improve the diagnostic accuracy of CFVR, which is in contrast to the findings of Baumgart et al. (11) in a small cohort of patients with single-vessel disease. A uniform CFVR distribution is described in patients without coronary artery disease (16). However, an apparently angiographically normal reference artery does not exclude the presence of atherosclerotic disease. This was shown in numerous studies using intravascular ultrasound imaging, where multivessel disease (among other variables) was an independent predictor of diffuse vessel wall abnormalities in angiographically normal reference segments (17). Heterogeneity of CFVR in the target and reference vessels in patients with multivessel coronary artery disease could also explain the failure of rCFVR to improve the relation of Doppler flow data with FFR in our patient cohort.
Perfusion scintigraphic results versus CFVR, rCFVR and FFR.
Previous validation studies using Doppler or pressure guide wires were predominantly performed in patients with single-vessel disease (Table 3), showing cut-off values of 1.7 to 2.0 for CFVR (3,4,7,8,18,19), 0.65 for rCFVR (8) and 0.68 to 0.75 for FFR (2,5,6,20). The results of this study show that the cut-off values validated for single-vessel disease are in accordance with the values obtained in two-vessel disease. The practical usefulness of the intracoronary-derived indexes is reflected in their applicability in a general set of patients. Therefore, currently used cut-off values in clinical practice (CFVR 2.0; FFR 0.75; rCFVR 0.65) (9) were compared with those found in the present study. This study supports the use of a cut-off value of 0.75 for FFR for clinical decision-making in both single- and two-vessel disease. Accordingly, a cut-off value of 0.65 can be used for rCFVR in clinical practice. For CFVR, a cut-off value of 2.0 is widely used for single-vessel disease. However, the present study reports a best cut-off value of 1.7 for two-vessel disease. As shown in Figure 1A, the sensitivity is equal for the range of 1.7 to 2.0 in the so-called "gray zone" ( 50% to 55%). Furthermore, several studies have demonstrated a safe postponement of percutaneous transluminal coronary angioplasty at CFVR values  2.0 (21–23). These arguments are in favor of using a CFVR cut-off value of 2.0 for clinical decision-making. Therefore, we suggest a cut-off value of 2.0 for CFVR in patients with single- or two-vessel coronary artery disease. As shown in Table 2, no significant differences were observed in the accuracy between CFVR, FFR and rCFVR using these predefined cut-off values.
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Table 3 Results of Previous Validation Studies for Intracoronary-Derived CFVR, FFR and rCFVR Versus the Results of Noninvasive Stress Testing
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The aforementioned studies showed 80% to 90% agreement with the results of several noninvasive tests. Our results of patients with two-vessel disease showed a lower agreement (77%) (Table 2) using the best cut-off values. This may be related to the patient group (i.e., multivessel vs. single-vessel coronary artery disease). It is known that perfusion scintigraphy has a limited capability, particularly in multivessel disease, to assign the perfusion defect to a specific epicardial coronary narrowing (24). It is possible that the assignment of the reversible perfusion defect, as detected by MIBI SPECT, to the perfusion territory of one of the three main coronary arteries (RCA, LAD and LCx) was inappropriate, especially in the so-called "watershed regions." Knowledge of the anatomic distribution pattern of the coronary arteries is a prerequisite for appropriate allocation of the culprit coronary artery. However, in this study, the panel of nuclear medicine physicians and the interventional cardiologist had no knowledge of the angiographic data and the results of MIBI SPECT, respectively, to ensure an objective comparison. Finally, hyperemia was differently induced during scintigraphy (intravenous dipyridamole) and cardiac catheterization (intracoronary adenosine). Recently, similar diagnostic accuracy was reported for both exercise stress testing and administration of adenosine or dipyridamole in inducing maximal hyperemia for myocardial perfusion scintigraphy (25). Furthermore, a recent study showed no difference in the hyperemic response, as measured by intracoronary Doppler flow velocity, between adenosine and adenosine triphosphate (both intravenously and intracoronarily administered) in comparison with papavarine (26). These findings indicate that different agents for vasodilation and routes of administration were not a major drawback of the current study.
Study limitations.
In this study, 161 of the 254 lesions were evaluated with CFVR, FFR and rCFVR; thus, 93 lesions were not measured with both intracoronary flow velocity and pressure. This was related to factors precluding assessment of intracoronary measurements (e.g., occlusions, coronary anatomy, lesion location). Because, at present, intracoronary flow velocity and pressure have to be measured with two different guide wires, it was at the operator’s discretion to use both wires in a particular lesion. In general, the more severe lesions were not suitable for evaluation with both flow velocity and pressure measurements. Most lesions studied were of intermediate severity (mean 57% by quantitative coronary angiography [range 35% to 85%]). However, clinical decision-making remains challenging in this cohort of patients with intermediate lesions, and quantitative coronary angiography is a poor predictor of the occurrence of events (27).
The detection of a reversible perfusion defect by perfusion scintigraphy, as well as the allocation of this defect to a coronary artery, was performed by an experienced panel of nuclear medicine physicians. In this study, 100 (79%) of the 127 patients (total of 254 lesions) showed one or more reversible defects on the scintigraphic images. As mentioned earlier, flow velocity and pressure measurements were performed in 161 of the total 254 lesions. Quantitative coronary angiography of these 161 lesions demonstrated 35% to 85% diameter stenosis. Only 52 (32%) of the 161 areas of interest were identified by the panel, by allocation of the perfusion defect to the territory of the culprit coronary vessel. This could explain the lower agreement found in the current study between the results of perfusion scintigraphy and hemodynamic variables.
Clinical implications.
The value of intracoronary hemodynamic measurements is important for clinical decision-making both during elective angiography in patients with coronary artery disease and in the setting of ad hoc percutaneous transluminal coronary angioplasty. This study shows that CFVR, rCFVR and FFR are three useful hemodynamic variables for clinical decision-making during cardiac catheterization in patients with two-vessel coronary artery disease. The currently used cut-off values for clinical decision-making in single-vessel disease (CFVR 2.0; FFR 0.75; and rCFVR 0.65) can be applied in patients with two-vessel disease. In our opinion, FFR is preferable, from a practical point of view, for clinical decision-making in patients with coronary artery disease as: 1) the cut-off value of 0.74 found in the present study is close to the value of 0.75 widely used in single-vessel disease; and 2) FFR is easy to measure, particularly for inexperienced operators. However, the present study shows that ROC analysis did not reveal significant differences between FFR, CFVR and rCFVR. Long-term follow-up is mandatory in these patients with discordant results between the invasive indexes and the results of perfusion scintigraphy to establish which of these diagnostic methods has the highest clinical relevance from a prognostic point of view.
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Acknowledgments
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The enthusiastic and skillful help of the paramedical personnel of the Cardiac Catheterization Laboratory (Head: Martin Meesterman, RN) and cardiology ward (Head: Sjouk Boomstra, RN), as well as the technicians of the department of Nuclear Medicine (Head Technician: Ankie Lagerwaard), are gratefully acknowledged. Marcel G. W. Dijkgraaf, PhD, is acknowledged for his useful statistical comments.
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Footnotes
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1 Dr. Piek is a clinical investigator for the Netherlands Heart Foundation (grant D96.020). This study was supported by the Dutch Health Insurance Board (grant 96-036); RADI Medical Systems, Uppsala, Sweden; and Endosonics, Rancho Cordova, California. 
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Detection of Lipid Core Coronary Plaques in Autopsy Specimens With a Novel Catheter-Based Near-Infrared Spectroscopy System
J. Am. Coll. Cardiol. Img.,
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A. A. Barmeyer, A. Stork, K. Muellerleile, C. Tiburtius, A. K. Schofer, T. A. Heitzer, T. Hofmann, G. Adam, T. Meinertz, and G. K. Lund
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Radiology,
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H. J. Verberne, M. Meuwissen, S. A. J. Chamuleau, B.-J. Verhoeff, B. L. F. van Eck-Smit, J. A. E. Spaan, J. J. Piek, and M. Siebes
Effect of simultaneous intracoronary guidewires on the predictive accuracy of functional parameters of coronary lesion severity
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[Abstract]
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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
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Comparison of Spiral Multidetector CT Angiography and Myocardial Perfusion Imaging in the Noninvasive Detection of Functionally Relevant Coronary Artery Lesions: First Clinical Experiences
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L. P. Salm, J. J. Bax, H. W. Vliegen, S. E. Langerak, P. Dibbets, J. W. Jukema, H. J. Lamb, E. K.J. Pauwels, A. de Roos, and E. E. van der Wall
Functional significance of stenoses in coronary artery bypass grafts: Evaluation by single-photon emission computed tomography perfusion imaging, cardiovascular magnetic resonance, and angiography
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[Abstract]
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J. L. Orford, A. Lerman, and D. R. Holmes
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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
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[Abstract]
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V. Voudris, D. Avramides, M. Koutelou, J. Malakos, A. Manginas, M. Papadakis, and D. V. Cokkinos
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[Abstract]
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M. G. Stoel, F. Zijlstra, and C. A. Visser
Frame Count Reserve
Circulation,
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[Abstract]
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N. H. J. Pijls
Is it time to measure fractional flow reserve in all patients?
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D V Cokkinos, A Manginas, and V Voudris
Coronary flow: clinical considerations
Heart,
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S. Hiraishi, H. Hirota, Y. Horiguchi, N. Takeda, N. Fujino, N. Ogawa, and Y. Nakahata
Transthoracic Doppler assessment of coronary flow velocity reserve in children with Kawasaki disease: Comparison with coronary angiography and thallium-201 imaging
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November 20, 2002;
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[Abstract]
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M. Siebes, S. A. J. Chamuleau, M. Meuwissen, J. J. Piek, and J. A. E. Spaan
Influence of hemodynamic conditions on fractional flow reserve: parametric analysis of underlying model
Am J Physiol Heart Circ Physiol,
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[Abstract]
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Abstract
Methods