Advertisement
Canadian Journal of Cardiology

Beyond Stenosis With Fractional Flow Reserve Via Computed Tomography and Advanced Plaque Analyses for the Diagnosis of Lesion-Specific Ischemia

Published:January 28, 2016DOI:https://doi.org/10.1016/j.cjca.2016.01.023

      Abstract

      In the treatment of stable coronary artery disease (CAD), the determination of stenosis severity by invasive coronary angiography (ICA) is a critical procedure, and for borderline lesions, the detection of ischemia through invasive fractional flow reserve (FFR) is the gold standard. With advances in computational fluid dynamics, FFR can now be calculated noninvasively using anatomic data from coronary computed tomographic angiography (CCTA). This technique is known as FFRCT. The purpose of this review is to summarize the science of FFRCT, describe its diagnostic accuracy, discuss its clinical and economic impact, and elucidate factors beyond stenosis severity that may mechanistically relate to lesion-specific ischemia. These factors include adverse atherosclerotic plaque characteristics such as positive remodelling, low-attenuation plaque, and spotty calcification, as well as aggregate plaque volume. These factors can be appreciated noninvasively by CCTA but not by ICA. The diagnostic accuracy of FFRCT, compared with the gold standard of FFR, has been validated in 3 prospective multicentre blinded core laboratory–controlled trials, and as a result FFRCT has been approved by the US Food and Drug Administration for clinical use. FFRCT has also been shown in a clinical utility trial to better identify patients without obstructive CAD when compared with standard noninvasive assessment of stable CAD, thereby avoiding unnecessary angiograms. In addition, the use of FFRCT has been shown to allow for a significant cost savings compared with traditional care. It is therefore important for cardiologists to appreciate the value of this important new methodology.

      Résumé

      Dans le cadre du traitement de la coronaropathie stable, la coronarographie invasive (CI) est une intervention essentielle qui permet de déterminer l’importance de la sténose. Dans le cas des lésions de grade limite, le dépistage de l’ischémie selon la mesure invasive de la réserve de débit fractionnaire est la norme de l’investigation à ce jour. Grâce à l’évolution des analyses numériques de la dynamique des fluides, il est désormais possible de calculer la réserve de débit fractionnaire de manière non invasive en utilisant les données anatomiques recueillies à l’aide d’une coronarographie par tomodensitométrie. Cet article résume cette méthode d’évaluation, traite de sa précision diagnostique et de son impact clinique et économique, en plus de fournir des éclaircissements relatifs aux caractéristiques qui vont au-delà de l’importance de la sténose coronaire et peuvent aider à comprendre le mécanisme de l’ischémie reliée à la lésion, notamment le remodelage positif de la plaque, la faible atténuation du signal au niveau de la plaque, les calcifications localisées et le volume global de la plaque. Il est désormais possible d’évaluer toutes ces caractéristiques de manière non invasive grâce à la coronarographie par tomodensitométrie, ce qui n’est pas possible avec la CE. La précision diagnostique de cette méthode non invasive comparée à celle de la méthode invasive a été validée par 3 études prospectives multicentriques contrôlées par un laboratoire central et son utilisation en clinique est désormais approuvée par la Food and Drug Administration des États-Unis. Dans le cadre d’une étude vérifiant l’utilité clinique, la coronarographie par tomodensitométrie s’est montrée plus efficace que la méthode non invasive traditionnelle d’évaluation de la coronaropathie stable pour déterminer quels patients étaient exempts de la forme obstructive de la maladie et a ainsi permis d’éviter des angiogrammes non nécessaires. Enfin, il a été démontré que la coronarographie par tomodensitométrie permettait des économies de coûts substantielles comparativement aux méthodes traditionnelles. Il importe donc que les cardiologues comprennent la valeur de cette nouvelle méthode d’évaluation de la coronaropathie stable.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Canadian Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Fihn S.D.
        • Gardin J.M.
        • Abrams J.
        • et al.
        2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
        J Am Coll Cardiol. 2012; 60: e44-e164
        • Gould K.L.
        • Lipscomb K.
        • Hamilton G.W.
        Physiologic 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
        • Lipscomb K.
        • Gould K.L.
        Mechanism of the effect of coronary artery stenosis on coronary flow in the dog.
        Am Heart J. 1975; 89: 60-67
        • Meijboom W.B.
        • Van Mieghem C.A.
        • van Pelt N.
        • 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. 2008; 52: 636-643
        • Tonino P.A.
        • Fearon W.F.
        • De Bruyne B.
        • et al.
        Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation.
        J Am Coll Cardiol. 2010; 55: 2816-2821
        • Tonino P.A.
        • De Bruyne B.
        • Pijls N.H.
        • et al.
        Fractional flow reserve versus angiography for guiding percutaneous coronary intervention.
        N Engl J Med. 2009; 360: 213-224
        • Shaw L.J.
        • Heller G.V.
        • Casperson P.
        • et al.
        Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424.
        J Nucl Cardiol. 2006; 13: 685-698
        • Pijls N.H.
        • Fearon W.F.
        • Tonino P.A.
        • et al.
        Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study.
        J Am Coll Cardiol. 2010; 56: 177-184
        • Pijls N.H.
        • van Schaardenburgh P.
        • Manoharan G.
        • et al.
        Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER Study.
        J Am Coll Cardiol. 2007; 49: 2105-2111
        • Patel M.R.
        Detecting obstructive coronary disease with CT angiography and noninvasive fractional flow reserve.
        JAMA. 2012; 308: 1269-1270
        • Abdulla J.
        • Pedersen K.S.
        • Budoff M.
        • Kofoed K.F.
        Influence of coronary calcification on the diagnostic accuracy of 64-slice computed tomography coronary angiography: a systematic review and meta-analysis.
        Int J Cardiovasc Imaging. 2012; 28: 943-953
        • Budoff M.J.
        • Dowe D.
        • Jollis J.G.
        • et al.
        Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial.
        J Am Coll Cardiol. 2008; 52: 1724-1732
        • Meijboom W.B.
        • Meijs M.F.
        • Schuijf J.D.
        • et al.
        Diagnostic accuracy of 64-slice computed tomography coronary angiography: a prospective, multicenter, multivendor study.
        J Am Coll Cardiol. 2008; 52: 2135-2144
        • Taylor C.A.
        • Fonte T.A.
        • Min J.K.
        Computational fluid dynamics applied to cardiac computed tomography for noninvasive quantification of fractional flow reserve: scientific basis.
        J Am Coll Cardiol. 2013; 61: 2233-2241
        • Park H.B.
        • Heo R.
        • óHartaigh B.
        • et al.
        Atherosclerotic plaque characteristics by CT angiography identify coronary lesions that cause ischemia: a direct comparison to fractional flow reserve.
        JACC Cardiovasc Imaging. 2015; 8: 1-10
        • Koo B.K.
        • Erglis A.
        • Doh J.H.
        • et al.
        Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study.
        J Am Coll Cardiol. 2011; 58: 1989-1997
        • Zarins C.K.
        • Taylor C.A.
        • Min J.K.
        Computed fractional flow reserve (FFTCT) derived from coronary CT angiography.
        J Cardiovasc Transl Res. 2013; 6: 708-714
        • Pijls N.H.
        • Van Gelder B.
        • Van der Voort P.
        • et al.
        Fractional flow reserve. A useful index to evaluate the influence of an epicardial coronary stenosis on myocardial blood flow.
        Circulation. 1995; 92: 3183-3193
        • Johnson N.P.
        • Toth G.G.
        • Lai D.
        • et al.
        Prognostic value of fractional flow reserve: linking physiologic severity to clinical outcomes.
        J Am Coll Cardiol. 2014; 64: 1641-1654
        • Pijls N.H.
        • Sels J.W.
        Functional measurement of coronary stenosis.
        J Am Coll Cardiol. 2012; 59: 1045-1057
        • Windecker S.
        • Kolh P.
        • Alfonso F.
        • et al.
        2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI).
        Eur Heart J. 2014; 35: 2541-2619
        • Levine G.N.
        • Bates E.R.
        • Blankenship J.C.
        • et al.
        2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions.
        J Am Coll Cardiol. 2011; 58: e44-e122
        • Kleiman N.S.
        Bringing it all together: integration of physiology with anatomy during cardiac catheterization.
        J Am Coll Cardiol. 2011; 58: 1219-1221
        • Morris P.D.
        • van de Vosse F.N.
        • Lawford P.V.
        • Hose D.R.
        • Gunn J.P.
        “Virtual” (computed) fractional flow reserve: current challenges and limitations.
        JACC Cardiovasc Interv. 2015; 8: 1009-1017
        • Precious B.
        • Blanke P.
        • Norgaard B.L.
        • Min J.K.
        • Leipsic J.
        Fractional flow reserve modeled from resting coronary CT angiography: state of the science.
        AJR Am J Roentgenol. 2015; 204: W243-W248
        • Min J.K.
        • Leipsic J.
        • Pencina M.J.
        • et al.
        Diagnostic accuracy of fractional flow reserve from anatomic CT angiography.
        JAMA. 2012; 308: 1237-1245
        • Norgaard B.L.
        • Leipsic J.
        • Gaur S.
        • et al.
        Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps).
        J Am Coll Cardiol. 2014; 63: 1145-1155
        • Leipsic J.
        • Yang T.H.
        • Thompson A.
        • et al.
        CT angiography (CTA) and diagnostic performance of noninvasive fractional flow reserve: results from the Determination of Fractional Flow Reserve by Anatomic CTA (DeFACTO) study.
        AJR Am J Roentgenol. 2014; 202: 989-994
        • Gaur S.
        • Bezerra H.G.
        • Lassen J.F.
        • et al.
        Fractional flow reserve derived from coronary CT angiography: variation of repeated analyses.
        J Cardiovasc Comput Tomogr. 2014; 8: 307-314
        • Douglas P.S.
        • Pontone G.
        • Hlatky M.A.
        • et al.
        Clinical outcomes of fractional flow reserve by computed tomographic angiography-guided diagnostic strategies vs. usual care in patients with suspected coronary artery disease: the prospective longitudinal trial of FFRCT: outcome and resource impacts study.
        Eur Heart J. 2015; 36: 3359-3367
        • Hlatky M.A.
        • De Bruyne B.
        • Pontone G.
        • et al.
        Quality of life and economic outcomes of assessing fractional flow reserve with computed tomography angiography: PLATFORM.
        J Am Coll Cardiol. 2015; 66: 2315-2323
        • Chinnaiyan K.M.
        • Raff G.L.
        • Ananthasubramaniam K.
        Coronary CT angiography after stress testing: an efficient use of resources? Implications of the Advanced Cardiovascular Imaging Consortium (ACIC) results.
        J Nucl Cardiol. 2012; 19: 649-657
        • Douglas P.S.
        • Hoffmann U.
        • Patel M.R.
        • et al.
        Outcomes of anatomical versus functional testing for coronary artery disease.
        N Engl J Med. 2015; 372: 1291-1300
        • Jensen J.M.
        • Voss M.
        • Hansen V.B.
        • et al.
        Risk stratification of patients suspected of coronary artery disease: comparison of five different models.
        Atherosclerosis. 2012; 220: 557-562
        • De Bruyne B.
        • Fearon W.F.
        • Pijls N.H.
        • et al.
        Fractional flow reserve-guided PCI for stable coronary artery disease.
        N Engl J Med. 2014; 371: 1208-1217
        • Baumann S.
        • Wang R.
        • Schoepf U.J.
        • et al.
        Coronary CT angiography-derived fractional flow reserve correlated with invasive fractional flow reserve measurements—initial experience with a novel physician-driven algorithm.
        Eur Radiol. 2015; 25: 1201-1207
        • Coenen A.
        • Lubbers M.M.
        • Kurata A.
        • et al.
        Fractional flow reserve computed from noninvasive CT angiography data: diagnostic performance of an on-site clinician-operated computational fluid dynamics algorithm.
        Radiology. 2015; 274: 674-683
        • Renker M.
        • Schoepf U.J.
        • Wang R.
        • et al.
        Comparison of diagnostic value of a novel noninvasive coronary computed tomography angiography method versus standard coronary angiography for assessing fractional flow reserve.
        Am J Cardiol. 2014; 114: 1303-1308
        • Nakazato R.
        • Shalev A.
        • Doh J.H.
        • Koo
        • et al.
        Aggregate plaque volume by coronary computed tomography angiography is superior and incremental to luminal narrowing for diagnosis of ischemic lesions of intermediate stenosis severity.
        J Am Coll Cardiol. 2013; 62: 460-467
        • Motoyama S.
        • Sarai M.
        • Harigaya H.
        • et al.
        Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome.
        J Am Coll Cardiol. 2009; 54: 49-57
        • Ahmadi A.
        • Kini A.
        • Narula J.
        Discordance between ischemia and stenosis, or PINSS and NIPSS: are we ready for new vocabulary?.
        JACC Cardiovasc Imaging. 2015; 8: 111-114
        • Choi G.
        • Lee J.M.
        • Kim H.J.
        • et al.
        Coronary artery axial plaque stress and its relationship with lesion geometry: application of computational fluid dynamics to coronary CT angiography.
        JACC Cardiovasc Imaging. 2015; 8: 1156-1166
        • De Bruyne B.
        • Hersbach F.
        • Pijls N.H.
        • et al.
        Abnormal epicardial coronary resistance in patients with diffuse atherosclerosis but “normal” coronary angiography.
        Circulation. 2001; 104: 2401-2406
        • Abbara S.
        • Arbab-Zadeh A.
        • Callister T.Q.
        • et al.
        SCCT guidelines for performance of coronary computed tomographic angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee.
        J Cardiovasc Comput Tomogr. 2009; 3: 190-204
        • Min J.K.
        • Koo B.K.
        • Erglis A.
        • et al.
        Effect of image quality on diagnostic accuracy of noninvasive fractional flow reserve: results from the prospective multicenter international DISCOVER-FLOW study.
        J Cardiovasc Comput Tomogr. 2012; 6: 191-199
        • Nørgaard B.L.
        • Gaur S.
        • Leipsic J.
        • et al.
        Influence of coronary calcification on the diagnostic performance of CT angiography derived FFR in coronary artery disease.
        JACC Cardiovasc Imaging. 2015; 8: 1045-1055
      1. ClinicalTrials.gov. Assessing diagnostic value of non-invasive FFRCT in coronary care (ADVANCE). Available at: https://clinicaltrials.gov/ct2/show/NCT02499679. Accessed August 14, 2015.

        • Min J.K.
        • Taylor C.A.
        • Achenbach S.
        • et al.
        Noninvasive fractional flow reserve derived from coronary CT angiography: clinical data and scientific principles.
        JACC Cardiovasc Imaging. 2015; 8: 1209-1222