Comparison of pressure-derived fractional flow reserve with poststenotic coronary flow velocity reserve for prediction of stress myocardial perfusion imaging results

doi:10.1016/0002-8703(95)90070-5

American Heart Journal

Volume 130, Issue 4, October 1995, Pages 723-733

https://doi.org/10.1016/0002-8703(95)90070-5 Get rights and content

Abstract

The physiologic importance of coronary stenoses can be assessed indirectly by stress myocardial perfusion imaging or directly by translesional pressure and flow measurements. The aims of this study were to compare myocardial fractional flow reserve (FFR_myo), a recently proposed index of lesion significance derived from hyperemic translesional pressure gradients, with directly measured poststenotic flow velocity reserve for the prediction of myocardial perfusion stress imaging results in corresponding vascular beds. Poststenotic coronary flow velocity (0.018-inch guide wire) and translesional pressure gradients (2.7F fluid-filled catheter) were measured at baseline and after intracoronary adenosine (12 to 18 μg) in 70 arteries (diameter stenosis: mean 56% ± 15%, range 14% to 94% by quantitative angiography). Coronary flow reserve was calculated as the ratio of hyperemic to basal mean flow velocity. FFR_myo was calculated during maximal hyperemia as equal to 1 — (hyperemic gradient [mean aortic pressure — 5]), where 5 is the assumed central venous pressure. Positive and negative predictive values and predictive accuracy for reversible stress myocardial perfusion abnormalities were computed. There was a significant correlation between pressure-derived FFR_myo and distal coronary flow reserve (r = 0.46; p < 0.0001). The strongest predictor of stress myocardial perfusion imaging results was the poststenotic coronary flow reserve (chi square = 33.2; p < 0.0001). The correlation between stress myocardial perfusion imaging and FFR_myo was also significant (chi square = 8.3; p < 0.005). There was no correlation between stress myocardial perfusion imaging and percentage diameter stenosis (chi square = 2.9; p = 0.10) or minimal lumen diameter (chi square = 0.47; p = 0.73). A poststenotic coronary flow reserve of ≤2 had a positive predictive value of 89% for regionally abnormal myocardial perfusion imaging abnormalities, whereas the positive predictive values of FFR_myo and angiographic percentage diameter stenosis were only 71% and 67% respectively. In conclusion, the predictive value of poststenotic coronary flow velocity reserve for stress-induced myocardial perfusion abnormalities exceeds that of the translesional FFR_myo. These findings should be considered when applying these techniques for clinical decision making in the assessment of coronary stenosis severity.

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In this review, the authors reflect upon the role of coronary physiology in the modern management of coronary artery disease. They critically appraise the scientific background of the instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR), from early experimental studies to validation studies against indexes of ischemia, to clinical trials assessing outcome. At this important juncture for the field, the authors make predictions for the future of physiological stenosis assessment, outlining developments for both iFR and FFR in new clinical domains beyond the confines of stable angina. With a focus on the evolving future of iFR and FFR, the authors describe how physiological assessment with iFR may advance its application from simply justifying to guiding revascularization.
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The present meta-analysis illustrates the accuracy of myocardial perfusion SPECT (MPS) to diagnose functional stenotic coronary artery disease (CAD) with fractional flow reserve (FFR) as standard reference.
All investigators screened and selected studies that compared MPS with FFR in symptomatic patients with suspected CAD. Patients and study characteristics were independently extracted by two investigators; differences were resolved by consensus.
13 articles, including 1,017 patients, 699 vessels were included in the study. No significant publication bias was detected (P = 0.65). At the patient level, the summary sensitivity and specificity were 77% (95% confidence interval [CI], 70–83%) and 77% (95%CI, 67–84%) for MPS. Vessel-level pooled sensitivity was 66% (95%CI, 57–74%) and specificity was 81% (95%CI, 70–89%). The overall diagnostic performance of MPS was moderate. [The area under the summary receiver operating characteristic (sROC) curve was 0.83]. No study influenced the pooled results larger than 0.03.
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Is discordance of coronary flow reserve and fractional flow reserve due to methodology or clinically relevant coronary pathophysiology?
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Citation Excerpt :
Similarly, a significant but modest correlation exists between CFR by PET and stress relative uptake as a whole (r = 0.36 [95% CI: 0.32 to 0.40], p < 0.001; ρ = 0.30, p < 0.001). Table 1 summarizes all the invasive literature for combined CFR and FFR measurements, both in the vessel of clinical interest and in reference or nonischemic vessels (11,12,17–36). As the normal range for noninvasive CFR is >4 in young, asymptomatic volunteers (6), the lower portion of Table 1 demonstrates that all studies examined subjects who had either small-vessel disease or at least mild diffuse disease, even in normal reference vessels.
The purpose of this study was to determine whether observed discordance between coronary flow reserve (CFR) and fractional flow reserve (FFR) is due to methodology or reflects basic coronary pathophysiology.
Despite the clinical importance of coronary physiological assessment, relationships between its 2 most common tools, CFR and FFR, remain poorly defined.
The worst CFR and stress relative uptake were recorded from 1,500 sequential cardiac positron emission tomography cases from our center. From the literature, we assembled all combined, invasive CFR-FFR measurements, including a subset before and after angioplasty. Both datasets were compared with a fluid dynamic model of the coronary circulation predicting relationships between CFR and FFR for variable diffuse and focal narrowing.
A modest but significant linear relationship exists between CFR and FFR both invasively (r = 0.34, p < 0.001) and using positron emission tomography (r = 0.36, p < 0.001). Most clinical patients undergoing CFR or FFR measurements have diffusely reduced CFR consistent with diffuse atherosclerosis or small-vessel disease. The theoretical model predicts linear relationships between CFR and FFR for progressive stenosis with slopes dependent on diffuse narrowing, matching observed data. Reported changes in CFR and FFR with angioplasty agree with model predictions of removing focal stenosis but leaving diffuse disease. Although CFR-FFR concordance is common, discordance is due to dominant or absent diffuse versus focal disease, reflecting basic pathophysiology.
CFR is linearly related to FFR for progressive stenosis superimposed on diffuse narrowing. The relative contributions of focal and diffuse disease define the slope and values along the linear CFR and FFR relationship. Discordant CFR and FFR values reflect divergent extremes of focal and diffuse disease, not failure of either tool. With such discordance observed by invasive and noninvasive techniques and also fitting fluid dynamic predictions, it reflects clinically relevant basic coronary pathophysiology, not methodology.
Wall shear over high degree stenoses pertinent to atherothrombosis
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Full vasodilation is implemented during the clinical measurement of fractional flow reserve (FFR) to estimate stenosis severity, defined as the ratio of maximal myocardial flow in the presence of the stenosis relative to the absence of the stenosis. FFR is commonly estimated by the ratio of pressure distal to a stenosis relative to the pressure proximal (aortic pressure), which monotonically decreases for severe stenoses that are greater than 50% (Tron et al., 1995; Baumgart et al., 1998; Shalman et al., 2001). Maximum shear rates in moderate stenoses scale with the square root of the Reynolds number (Siegel et al., 1994).
Atherothrombosis can induce acute myocardial infarction and stroke by progressive stenosis of a blood vessel lumen to full occlusion. Since thrombus formation and embolization may be shear-dependent, we quantify the magnitude of shear rates in idealized severely stenotic coronary arteries (≥75% by diameter) using computational fluid dynamics to characterize the shear environment that may exist during atherothrombosis. Maximum shear rates in severe short stenoses were found to exceed 250,000 s⁻¹ (9500 dynes/cm²) and can reach a peak value of 425,000 s⁻¹ for a 98% stenosis. These high shear rates exceed typical shear used for in vitro blood flow experiments by an order of magnitude, indicating the need to examine thrombosis at very high shear rates. Pulsatility and stenosis eccentricity were found to have minor effects on the maximum wall shear rates in severe stenoses. In contrast, increases in the stenosis length reduced the maximum shear to 107,000 s⁻¹ (98% stenosis), while surface roughness could increase focal wall shear rates to a value reaching 610,000 s⁻¹ (90% stenosis). The “shear histories” of circulating platelets in these stenoses are far below reported activation thresholds. Platelets may be required to form bonds in 5 μs and resist shear forces reaching 8000 pN per platelet. Arterial thrombosis occurs in the face of pathological high shear stress, creating rapid and strong bonds without prior activation of circulating platelets.
Physiologic Lesion Assessment During Percutaneous Coronary Intervention
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The ischemic cut-off threshold for CFR is from less than 2.0 to 2.5.2,3,9 This threshold is based on a series of studies comparing CFR values in vessels with differing levels of angiographic stenosis with evidence of reversible myocardial ischemia in the corresponding myocardial territory, as detected by standard noninvasive functional tests (Table 1).11–26 Pooled results from multiple studies confirm that a CFR of less than 2.0 has a sensitivity of 86% to 92%, specificity of 89% to 100%, positive predictive value of 84% to 100%, negative predictive value of 77% to 95%, and predictive accuracy of 89% to 96% for detection of reversible myocardial ischemia.
Meta-Analysis of Fractional Flow Reserve Versus Quantitative Coronary Angiography and Noninvasive Imaging for Evaluation of Myocardial Ischemia
2007, American Journal of Cardiology
Citation Excerpt :
Of those, we excluded 45 (ineligible diagnostic test comparison n = 11, <5 patients n = 1, review n = 2, nonhuman studies n = 1, all patients/no patients with positive results n = 10, duplicate data from same team n = 7, missing information for 2 × 2 table n = 13 [all addressing QCA; 1 also addressed noninvasive imaging against FFR]). Overall, 31 eligible studies were retained for the meta-analysis.2,3,5,7,9–35 Studies performed by the same team were scrutinized and in all cases they provided complementary, nonoverlapping information.
We performed a meta-analysis of 31 studies comparing the results of fractional flow reserve (FFR) against quantitative coronary angiography (QCA) and/or noninvasive imaging of the same lesions. Studies were retrieved from PubMed (last search February 2006). Across 18 studies (1,522 lesions), QCA had a random effects sensitivity of 78% (95% confidence interval [CI] 67 to 86) and specificity of 51% (95% CI 40 to 61) against FFR (0.75 cutoff). Overall concordances were 61% for lesions with diameter stenosis 30% to 70%, 67% for stenoses >70%, and 95% for stenoses <30%. Compared with noninvasive imaging (21 studies, 1,249 lesions), FFR had a sensitivity of 76% (95% CI 69 to 82) and specificity of 76% (95% CI 71 to 81) by random effects. Summary receiver-operator characteristic estimates were similar. Most data addressed comparisons with perfusion scintigraphy (976 lesions, sensitivity 75%, specificity 77%), and some data were also available for dobutamine stress echocardiography (273 lesions, sensitivity 82%, specificity 74%). In conclusion, QCA does not predict the functional significance of coronary lesions. FFR shows modest concordance with noninvasive imaging tests. The prognostic implications of discordant FFR and imaging results need further study.

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^☆: Supported in part by a Lavoisier Grant from the French Ministère des Affaires Etrangères (to C. T.).

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Comparison of pressure-derived fractional flow reserve with poststenotic coronary flow velocity reserve for prediction of stress myocardial perfusion imaging results☆

Abstract

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Relation between myocardial blood flow and the severity of coronary artery stenosis

N Engl J Med

Validation of a Doppler guidewire for intravascular measurement of coronary artery flow velocity

Circulation