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Is Instantaneous Wave-Free Ratio a New Standard of Care for Physiologic Assessment of Coronary Lesions?

2017; Lippincott Williams & Wilkins; Volume: 136; Issue: 24 Linguagem: Inglês

10.1161/circulationaha.117.029567

1524-4539

Morton J. Kern, Arnold H. Seto,

Cardiovascular Health and Disease Prevention

HomeCirculationVol. 136, No. 24Is Instantaneous Wave-Free Ratio a New Standard of Care for Physiologic Assessment of Coronary Lesions? Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBIs Instantaneous Wave-Free Ratio a New Standard of Care for Physiologic Assessment of Coronary Lesions?More Questions Than Answers Morton J. Kern, MD and Arnold H. Seto, MD Morton J. KernMorton J. Kern Departments of Medicine (M.J.K.) and Cardiology (A.H.S.), Veterans Administration Long Beach Health Care System, University of California, Irvine. and Arnold H. SetoArnold H. Seto Departments of Medicine (M.J.K.) and Cardiology (A.H.S.), Veterans Administration Long Beach Health Care System, University of California, Irvine. Originally published12 Dec 2017https://doi.org/10.1161/CIRCULATIONAHA.117.029567Circulation. 2017;136:2295–2297After >20 years since the proof of concept, fractional flow reserve (FFR) has become an invasive standard for lesion assessment in the cath laboratory. The fundamental premise that allowed for the transition from traditional coronary flow reserve to a pressure-only flow reserve (ie, fraction of normal flow or FFR) required maximal hyperemia to create a linear relationship between pressure and flow.1 Compared with resting pressure ratios, hyperemia produces better separation of the families of pressure/flow curves characterizing obstructive from nonobstructive stenotic lesions. Validation of FFR against multiple stress test modalities demonstrated that regionally specific myocardial ischemia could be identified. The proof of clinical value came from favorable randomized trial results with reduced adverse event rates and costs for FFR-directed PCI (FAME I [Fractional Flow Reserve versus Angiography for Guiding PCI in Patients with Multivessel Coronary Artery Disease trial I]) and the superiority of FFR-guided revascularization over medical therapy for FFR obstructive lesions (FAME II [Fractional Flow Reserve versus Angiography for Guiding PCI in Patients with Multivessel Coronary Artery Disease trial II]).Despite its strengths for lesion assessment over angiography alone, the interventional community was slow to adopt FFR for reasons, either perceived or real, that included additional time, cost, loss of procedural reimbursement, and use of adenosine. Nonetheless, FFR use has continued to grow as clinical studies covered new areas such as non–ST-segment elevation myocardial infarction and ST-segment elevation myocardial infarction, coronary artery bypass grafting results, and complex left main disease.In 2012, Dr Justin Davies from Imperial College in London introduced a new concept, the instantaneous wave-free ratio (iFR), a resting translesional pressure ratio taken during a specific diastolic interval in which the natural microvascular resistance is constant (but not minimal), and therefore, in part, meeting the criteria of FFR without inducing hyperemia (ie, with adenosine).2 Comparative studies showed that iFR had an 80% correspondence with FFR. Subsequently, a similar analysis (RESOLVE [multicenter core laboratory comparison of the instantaneous wave-free ratio and resting Pd/Pa with fractional flow reserve]) suggested that iFR could be used initially in a hybrid fashion with 100% correspondence for iFR <0.84 with FFR 0.94 with FFR >0.80. This year, the results of the first 2 large, randomized trials of iFR were presented at the American College of Cardiology annual scientific sessions prompting many to ask, "Is iFR a new standard in the cath laboratory?"To briefly recap, the DEFINE-FLAIR trial (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation)3 (n=2492) and the iFR-SWEDEHEART trial (Evaluation of iFR vs FFR in Stable Angina or Acute Coronary Syndrome)4 (n=2109) tested whether iFR-guided percutaneous coronary intervention (PCI) was noninferior to FFR-guided coronary revascularization. The 2 trials had nearly identical trial designs and used the same primary composite end point of all-cause mortality, nonfatal myocardial infarction, and unplanned revascularization. At 12 months, both studies demonstrated noninferiority to FFR (DEFINE-FLAIR 6.8% versus 7.0% for iFR versus FFR, noninferiority P<0.001; iFR SWEDEHEART 6.7% versus 6.1%, noninferiority P=0.007). Because adenosine was avoided, iFR patients had shorter procedure times (by 4.5 minutes) and fewer adenosine-related effects. There were also fewer positive lesions with iFR, translating to fewer referrals for PCI and coronary artery bypass grafting (Table). Although limitations of studying low-risk populations and the large noninferiority margins used can be discussed, the clinical comparison with FFR will lead many to adopt iFR for use in practice.Table. FFR Versus iFR ComparisonVariableFFRIFRQuantity outcome data and length of experience*†Resistance to technical errors (damping, drift, equalization, changing basal flow)†‡• Small equalization errors are more significant• Administration of nitrates, contrast, saline, or after PCI alters resting stateProcedure time(IC adenosine)(IV adenosine)†‡**Avoidance of transient adenosine side effects‡(Less with IC adenosine)*Cost savings†Fewer stents compared with angiographic guidance*No adenosine, fewer revascularization procedures compared with FFRPullback measurements† Variability of hyperemic state*Availability*Can be performed with any of the 5 currently available systems and types of sensors/platforms‡Requires use of Volcano/Philips technologyFFR indicates fractional flow reserve; IC, intracoronary; IV, intravenous; and iFR, instantaneous wave-free ratio.*Favorable result.†Average.‡Less favorable.iFR QuestionsThe use of iFR introduced the concept that hyperemia is not required to demonstrate the ischemic potential of a stenosis and challenged the fundamentals underlying both vasodilator nuclear stress testing as well as FFR. The precepts of vasodilator radionuclide stress testing require hyperemia to induce regional differences in perfusion. It is also a concept that undermines the fundamental assumption behind FFR—that pressure is related to flow only when resistance is constant and minimal.Many questions are still debated in scientific meetings and in the literature. Is resting microvascular resistance during the wave-free interval low enough for pressure to approximate flow? Is it more important that resistance be minimal or constant? Does the full-cycle pressure ratio (ie, pressure ratio averaged over both systole and diastole) during hyperemia provide a better marker of obstructive disease than the diastolic only pressure ratio (ie, iFR)? Does the variable hyperemic response to adenosine limit the accuracy of FFR? For both severe and minimal stenoses, resting and hyperemic indices are nearly always concordant, but which method is the superior indicator remains unclear for the 20% with discordant results. The absence of a true gold standard for ischemia blurs the discriminative ability of the hyperemic compared with resting indices. iFR, distal/aortic pressure ratio, basal stenosis resistance, and FFR all have an 80% correspondence to a standard of hyperemic stenosis resistance or coronary flow reserve. We question whether hyperemic stenosis resistance and coronary flow reserve are truly ischemic standards. Recently, using positron emission tomography perfusion results as a standard, no difference was observed between iFR and FFR to predict ischemia.5 Although the derivation of the FFR concept remains elegant and straightforward, is the iFR/resting indices approach too reductionist?The gold standard for any scientific medical test is its real-life usefulness (ie, clinical outcomes). iFR appears to be noninferior to FFR on this basis. However, perhaps the significant adverse clinical events after PCI are too infrequent to discern with sufficient precision whether iFR or FFR is superior. Random events unrelated to the ischemia-testing procedure (including adequacy of stent expansion, adherence to antiplatelet therapy, performance of PCI, and nontarget vessel infarctions) could potentially obscure true results and bias comparisons toward the null. Similarly, if iFR is concordant with FFR in 80% of cases, then the outcomes of the remaining 20% that are discordant may represent a better comparison between the 2 techniques than was tested in DEFINE-FLAIR and iFR-SWEDEHEART. Unfortunately, iFR/FFR discordance occurs more frequently in the grey zone, where the benefits of PCI are also often equivocal. Last, because the 2 randomized iFR studies had average FFR values (0.83) that were higher than FAME (0.71), do we have enough data in higher risk angiographic subsets to accept iFR as an FFR equivalent? Such questions remain to be answered by ongoing and future studies.Going ForwardiFR streamlines lesion assessment and is now part of the coronary hemodynamic tool box in many cath labs (recall that not every laboratory has the iFR proprietary software). For the lower risk patients as tested in the iFR outcome studies,3,4 the use of iFR reduced referrals for revascularization without increased adverse events. For complex anatomy, including serial or diffuse disease assessment, the iFR technique appears to be particularly helpful for pullback measurements as well as rapid multivessel testing. At this time, to replace FFR, iFR will need more long-term outcome studies, more independent validations versus ischemia testing, and greater experience in more diverse patient risk groups. From our perspective, iFR has disrupted conventional wisdom. While awaiting answers, it will be more widely adopted and, along with other novel physiological approaches (eg, FFR-CT), will enhance best practices for our patients with coronary artery disease.DisclosuresDr Kern is a consultant and speaker for Abbott/St Jude, Philips/Volcano, Acist Medical Inc, Opsens Inc, and Heartflow Inc. Dr Seto reports no conflicts of interest.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Circulation is available at http://circ.ahajournals.org.Correspondence to: Morton J. Kern, MD, Chief of Medicine, Veterans Administration Long Beach Health Care System, 5901 East 7th Street, Long Beach, CA 90822. E-mail [email protected]References1. 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; 87:1354–1367.LinkGoogle Scholar2. Sen S, Escaned J, Malik IS, Mikhail GW, Foale RA, Mila R, Tarkin J, Petraco R, Broyd C, Jabbour R, Sethi A, Baker CS, Bellamy M, Al-Bustami M, Hackett D, Khan M, Lefroy D, Parker KH, Hughes AD, Francis DP, Di Mario C, Mayet J, Davies JE. Development and validation of a new adenosine-independent index of stenosis severity from coronary wave-intensity analysis: results of the ADVISE (ADenosine Vasodilator Independent Stenosis Evaluation) study.J Am Coll Cardiol. 2012; 59:1392–1402. doi: 10.1016/j.jacc.2011.11.003.CrossrefMedlineGoogle Scholar3. Davies JE, Sen S, Dehbi HM, Al-Lamee R, Petraco R, Nijjer SS, Bhindi R, Lehman SJ, Walters D, Sapontis J, Janssens L, Vrints CJ, Khashaba A, Laine M, Van Belle E, Krackhardt F, Bojara W, Going O, Härle T, Indolfi C, Niccoli G, Ribichini F, Tanaka N, Yokoi H, Takashima H, Kikuta Y, Erglis A, Vinhas H, Canas Silva P, Baptista SB, Alghamdi A, Hellig F, Koo BK, Nam CW, Shin ES, Doh JH, Brugaletta S, Alegria-Barrero E, Meuwissen M, Piek JJ, van Royen N, Sezer M, Di Mario C, Gerber RT, Malik IS, Sharp ASP, Talwar S, Tang K, Samady H, Altman J, Seto AH, Singh J, Jeremias A, Matsuo H, Kharbanda RK, Patel MR, Serruys P, Escaned J. Use of the instantaneous wave-free ratio or fractional flow reserve in PCI.N Engl J Med. 2017; 376:1824–1834. doi: 10.1056/NEJMoa1700445.CrossrefMedlineGoogle Scholar4. Götberg M, Christiansen EH, Gudmundsdottir IJ, Sandhall L, Danielewicz M, Jakobsen L, Olsson SE, Öhagen P, Olsson H, Omerovic E, Calais F, Lindroos P, Maeng M, Tödt T, Venetsanos D, James SK, Kåregren A, Nilsson M, Carlsson J, Hauer D, Jensen J, Karlsson AC, Panayi G, Erlinge D, Fröbert O; iFR-SWEDEHEART Investigators. Instantaneous wave-free ratio versus fractional flow reserve to guide PCI.N Engl J Med. 2017; 376:1813–1823. doi: 10.1056/NEJMoa1616540.CrossrefMedlineGoogle Scholar5. Hwang D, Jeon KH, Lee JM, Park J, Kim CH, Tong Y, Zhang J, Bang JI, Suh M, Paeng JC, Na SH, Cheon GJ, Cook CM, Davies JE, Koo BK. Diagnostic performance of resting and hyperemic invasive physiological indices to define myocardial ischemia: validation with (13)N-ammonia positron emission tomography.JACC Cardiovasc Interv. 2017; 10:751–760. doi: 10.1016/j.jcin.2016.12.015.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By VERSACI F, CONTE M, VAN'T VEER M, LALANCETTE S, OLDROYD K, CALCAGNO S and BIONDI ZOCCAI G A novel algorithm for the computation of the diastolic pressure ratio in the invasive assessment of the functional significance of coronary artery disease, Panminerva Medica, 10.23736/S0031-0808.20.04202-0, 63:2 Fontes-Carvalho R, Oliveira G, Gonçalves L and Rochitte C (2019) The year in cardiology 2018: ABC Cardiol and RPC at a glance, Revista Portuguesa de Cardiologia (English Edition), 10.1016/j.repce.2019.02.010, 38:2, (73-81), Online publication date: 1-Feb-2019. Kerkhof P, Peace R and Handly N (2019) Ratiology and a Complementary Class of Metrics for Cardiovascular Investigations, Physiology, 10.1152/physiol.00056.2018, 34:4, (250-263), Online publication date: 1-Jul-2019. Fontes‐Carvalho R, Moraes de Oliveira G, Gonçalves L and Rochitte C (2019) O ano de 2018 em Cardiologia: uma visão geral da ABC Cardiol e RPC, Revista Portuguesa de Cardiologia, 10.1016/j.repc.2019.01.004, 38:2, (73-81), Online publication date: 1-Feb-2019. Bravo Baptista S and Raposo L (2018) Coronary pressure (sometimes) lies…, Revista Portuguesa de Cardiologia, 10.1016/j.repc.2018.05.001, 37:6, (521-523), Online publication date: 1-Jun-2018. Bravo Baptista S and Raposo L (2018) Coronary pressure (sometimes) lies…, Revista Portuguesa de Cardiologia (English Edition), 10.1016/j.repce.2018.06.004, 37:6, (521-523), Online publication date: 1-Jun-2018. Faes T, Meer R, Heyndrickx G and Kerkhof P (2020) Fractional Flow Reserve Evaluated as Metric of Coronary Stenosis — A Mathematical Model Study, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2019.00189, 6 December 12, 2017Vol 136, Issue 24 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.117.029567PMID: 29229617 Originally publishedDecember 12, 2017 Keywordscoronary hemodynamicsiFRFFRPDF download Advertisement SubjectsHemodynamics