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      Relationship between FFR, CFR and coronary microvascular resistance – Practical implications for FFR-guided percutaneous coronary intervention

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          Abstract

          Objective

          The aim was threefold: 1) expound the independent physiological parameters that drive FFR, 2) elucidate contradictory conclusions between fractional flow reserve (FFR) and coronary flow reserve (CFR), and 3) highlight the need of both FFR and CFR in clinical decision making. Simple explicit theoretical models were supported by coronary data analyzed retrospectively.

          Methodology

          FFR was expressed as a function of pressure loss coefficient, aortic pressure and hyperemic coronary microvascular resistance. The FFR-CFR relationship was also demonstrated mathematically and was shown to be exclusively dependent upon the coronary microvascular resistances. The equations were validated in a first series of 199 lesions whose pressures and distal velocities were monitored. A second dataset of 75 lesions with pre- and post-PCI measures of FFR and CFR was also analyzed to investigate the clinical impact of our hemodynamic reasoning.

          Results

          Hyperemic coronary microvascular resistance and pressure loss coefficient had comparable impacts (45% and 49%) on FFR. There was a good concordance ( y = 0.96 x − 0.02, r 2 = 0.97) between measured CFR and CFR predicted by FFR and coronary resistances. In patients with CFR < 2 and CFR/FFR ≥ 2, post-PCI CFR was significantly >2 (p < 0.001), whereas it was not (p = 0.94) in patients with CFR < 2 and CFR/FFR < 2.

          Conclusion

          The FFR behavior and FFR-CFR relationship are predictable from basic hemodynamics. Conflicting conclusions between FFR and CFR are explained from coronary vascular resistances. As confirmed by our results, FFR and CFR are complementary; they could jointly contribute to better PCI guidance through the CFR-to-FFR ratio in patients with coronary artery disease.

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          Most cited references24

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          Coronary Flow Reserve and Microcirculatory Resistance in Patients With Intermediate Coronary Stenosis.

          The prognostic impact of microvascular status in patients with high fractional flow reserve (FFR) is not clear.
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            Is discordance of coronary flow reserve and fractional flow reserve due to methodology or clinically relevant coronary pathophysiology?

            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. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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              Role of variability in microvascular resistance on fractional flow reserve and coronary blood flow velocity reserve in intermediate coronary lesions.

              Fractional flow reserve (FFR) and coronary blood flow velocity reserve (CFR) represent physiological quantities used to evaluate coronary lesion severity and to make clinical decisions. A comparison between the outcomes of both diagnostic techniques has not been performed in a large cohort of patients with intermediate coronary lesions. FFR and CFR were assessed in 126 consecutive patients with 150 intermediate coronary lesions (between 40% and 70% diameter stenosis by visual assessment). Agreement between outcomes of FFR and CFR, categorized at cut-off values of 0.75 and 2.0, respectively, was observed in 109 coronary lesions (73%), whereas discordant outcomes were present in 41 lesions (27%). In 26 of these 41 lesions, FFR was or=2.0 (group A); in the remaining 15 lesions, FFR was >or=0.75 and CFR<2.0 (group B). Minimum microvascular resistance, defined as the ratio of mean distal pressure to average peak blood flow velocity during maximum hyperemia, showed a large variability (overall range, 0.65 to 4.64 mm Hg x cm(-1) x s(-1)) and was significantly higher in group B than in group A (2.42+/-0.77 versus 1.91+/-0.70 mm Hg x cm(-1) x s(-1); P:=0.034). Our findings demonstrate the prominent role of microvascular resistance in modulating the relationship between FFR and CFR and emphasize the importance of combined pressure and flow velocity measurements to evaluate coronary lesion severity and microvascular involvement.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: ResourcesRole: Writing – review & editing
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 January 2019
                2019
                : 14
                : 1
                : e0208612
                Affiliations
                [1 ] CREATIS, INSERM U1206, Université Lyon 1, INSA Lyon, Villeurbanne, France
                [2 ] Department of Cardiology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, France
                [3 ] AMC Heart Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
                [4 ] Department of Cardiology, Tergooi Hospital, Blaricum, The Netherlands
                [5 ] Department of Cardiology, Amphia Hospital, Breda, The Netherlands
                [6 ] Imperial College London, London, United Kingdom
                Universita degli Studi Magna Graecia di Catanzaro, ITALY
                Author notes

                Competing Interests: Justin Davies is consultant for Medtronic and Philips-Volcano and has received research funding from these companies. All other authors have no relevant disclosures. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-8552-1475
                Article
                PONE-D-18-11143
                10.1371/journal.pone.0208612
                6322913
                30616240
                11d03b7e-7db4-4e22-aaec-5d4f2f7949b2
                © 2019 Garcia et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 13 April 2018
                : 20 November 2018
                Page count
                Figures: 10, Tables: 0, Pages: 16
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Stenosis
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Stenosis
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Cardiovascular Procedures
                Angioplasty
                Coronary Angioplasty
                Medicine and Health Sciences
                Hematology
                Hemodynamics
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                Vascular Medicine
                Ischemia
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                Diagnostic Medicine
                Signs and Symptoms
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                Medicine and Health Sciences
                Pathology and Laboratory Medicine
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                Lesions
                Biology and Life Sciences
                Physiology
                Physiological Parameters
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                Blood Flow
                Biology and Life Sciences
                Physiology
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                Medicine and Health Sciences
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