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Association of Coronary Stenosis and Plaque Morphology with Fractional Flow Reserve and Outcomes

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Association of Coronary Stenosis and Plaque Morphology with Fractional Flow Reserve and Outcomes Clinical Review & Education Review Association of Coronary Stenosis and Plaque Morphology With Fractional Flow Reserve and Outcomes Amir Ahmadi, MD; Gregg W. Stone, MD; Jonathon Leipsic, MD; Patrick W. Serruys, MD, PhD; Leslee Shaw, PhD; Harvey Hecht, MD; Graham Wong, MD; Bjarne Linde Nørgaard, MD, PhD; Patrick T. O’Gara, MD; Y. Chandrashekhar, MD; Jagat Narula, MD, PhD, MACC CME Quiz at jamanetworkcme.com and IMPORTANCE Obstructive coronary lesions with reduced luminal dimensions may result in CME Questions page 372 abnormal regional myocardial blood flow as assessed by stress-induced myocardial perfusion imaging or a significant fall in distal perfusion pressure with hyperemia-induced vasodilatation (fractional flow reserve [FFR] Յ0.80). An abnormal FFR has been demonstrated to identify high-risk lesions benefitting from percutaneous coronary Author Affiliations: Division of intervention while safely allowing revascularization to be deferred in low-risk lesions, Cardiology, Icahn School of Medicine resulting in a decrease in the number of revascularization procedures as well as substantially at Mount Sinai, New York, New York reduced death and myocardial infarction. While FFR identifies hemodynamically significant (Ahmadi, Hecht, Narula); Division of Cardiology and Radiology, University lesions likely to produce ischemia-related symptoms, it remains less clear as to why it might of British Columbia, Vancouver, predict the risk of acute coronary syndromes, which are usually due to plaque rupture and Canada (Ahmadi, Leipsic, Wong); coronary thrombosis. Division of Cardiology, Columbia University Medical Center, Cardiovascular Research Foundation, OBSERVATIONS Although the atherosclerotic plaques with large necrotic cores (independent New York, New York (Stone); Division of the degree of luminal stenosis) are known to be associated with vulnerability to rupture of Cardiology, Imperial College, and acute coronary syndromes, emerging evidence also suggests that they may induce London, England (Serruys); Division of Cardiology, Emory University greater rates of ischemia and reduced FFR compared with non–lipid-rich plaques also School of Medicine, Atlanta, Georgia independent of the degree of luminal narrowing. It is proposed that the presence of large (Shaw); Division of Cardiology, necrotic cores within the neointima may be associated with the inability of the vessel to dilate Aarhus University Hospital, Skejby, Denmark (Nørgaard); Division of and may predispose to ischemia and abnormal FFR. Cardiology, Brigham and Women’s Hospital, Harvard Medical School, CONCLUSIONS AND RELEVANCE Having a normal FFR requires unimpaired vasoregulatory Boston, Massachusetts (O’Gara); ability and significant luminal stenosis. Therefore, FFR should identify lesions that are unlikely Division of Cardiology, University of Minnesota School of Medicine, to possess large necrotic core, rendering them safe for treatment with medical therapy alone. Minneapolis (Chandrashekhar); Further studies are warranted to determine whether revascularization decisions in patients Division of Cardiology, Veterans with stable coronary artery disease could be improved by assessment of both plaque Affairs Medical Center, Minneapolis composition and ischemia. (Chandrashekhar). Corresponding Author: Jagat Narula, MD, PhD, Icahn School of JAMA Cardiol. 2016;1(3):350-357. doi:10.1001/jamacardio.2016.0263 Medicine at Mount Sinai, One Published online April 20, 2016. Gustave L. Levy Place, New York, NY 10029 ([email protected]). he Fractional Flow Reserve Versus Angiography for Multi- nary thrombosis, which is usually caused by lipid-rich plaques with vessel Evaluation (FAME) trial1,2 demonstrated that in pa- distinct histological features.5-13 These observations prompted us T tients with stable ischemic heart disease, an FFR-guided to explore whether plaque features of vulnerability and their strategy to identify hemodynamically significant lesions requiring physiologic properties are associated, causing a relevant pressure percutaneous coronary intervention (PCI) can safely defer revascu- gradient across the lesion detectable by FFR. larization in lower-risk lesions and reduce the number of proce- dures and rates of future urgent revascularization due to unstable angina or myocardial infarction (MI) compared with lesion selec- Severity of Luminal Stenosis and FFR tion by angiography alone. The FAME 2 trial3,4 extended these find- ings and demonstrated that deferring PCI in lesions with an abnor- Ischemia is best defined as an inadequate supply of oxygen relative mal FFR results in high rates of progressive ischemic symptoms, to myocardial demand. The most widely used tests to assess ische- unstable angina, and MI, which require revascularization within 1 to miaaremyocardialperfusionimaging(MPI)(noninvasive)andFFR(in- 2 years. These outcomes could be prevented by PCI.1-4 Although FFR vasive).MyocardialperfusionimagingandFFRusetheabnormalblood identifies hemodynamically significant lesions likely to produce flowintheaffectedvesselsasasurrogatemarkerforischemia.Inturn, ischemia-related symptoms, less clear is why FFR might predict the this abnormal blood flow is related to relative or complete inability of subsequent risk for ACS resulting from plaque rupture and coro- the vessel to dilate on stress. Although the detection of ischemia is 350 JAMA Cardiology June 2016 Volume 1, Number 3 (Reprinted) jamacardiology.com Copyright 2016 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 Coronary Stenosis, Fractional Flow Reserve, and Outcomes Review Clinical Review & Education Figure 1. Correlation Between the Degree of Luminal Stenosis by Coronary Angiography and Ischemia Detected by Fractional Flow Reserve (FFR) A FAMEAME tritrialal B IRISIRIS FFR trialtrial 1.00 1.1 SWOI 1.01.0 0.88 e 0.90.9 rv ese 0.80.8 0.66 w R o 0.70.7 l Fl a 0.44 n o 0.6 cti a r Fractional Flow Reserve Flow Fractional Reserve Flow Fractional F 0.50.5 0.2 0.40.4 IWOS 0 0.30.3 50-70 71-90 91-99 0 20 40 60 80 100100 LuminalLuminal Stenosis, % LuminalLuminal Stenosis, % A, In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation stenosis had an FFR of greater than 0.80 (FFR-verified SWOI) (entire light blue (FAME) trial, among the 623 lesions with 50% to 70% stenosis, 218 (35.0%) area), whereas 75 of 461 lesions (16.3%) with less than 50% luminal stenosis had an FFR of 0.80 or less (FFR-verified ischemia without significant stenosis had an FFR of 0.80 or less (FFR-verified IWOS) (light brown area). Using a cut [IWOS]). Among 520 lesions with 71% to 90% stenosis, 104 (20.0%) point for a severe stenosis diameter of 70%, a large proportion of lesions with demonstrated an FFR of greater than 0.80 (FFR-verified stenosis without less than 70% angiographic diameter stenosis had an FFR of 0.80 or less ischemia [SWOI]). Boxes indicate first and third quartiles; horizontal lines in (IWOS; entire red area). Among lesions with 50% to 70% angiographic boxes, median; whiskers, minimum and maximum data distribution (modified diameter stenosis, approximately half were positive for FFR and half were from Tonino et al18). B, In a prospective study of 1000 patients (Study of the negative for FFR (ie, no predictive value). Data points indicate degree of Natural History of FFR Guided Percutaneous Coronary Intervention16 [IRIS stenosis and corresponding FFR (modified from Park et al15). FFR]), 343 of 605 coronary lesions (56.7%) with less than 50% angiographic likely to be indicative of a severe epicardial coronary artery stenosis,14 cases of MPI-verified SWOI may be explained by short lesion length, thisassociationisnotperfect.2,15,16 Someseverelystenoticlesionsmay redundancy of the arterial supply through collateral vessel forma- not result in detectable ischemia (stenosis without ischemia [SWOI]), tion, and a limited myocardial territory supplied by the diseased ar- whereas other lesions with only a mild to moderate degree of angio- tery.As regards FFR, features such as lesion length, entrance angle, graphic stenosis may induce ischemia (ischemia without significant exit angle, size of the reference vessel, and absolute flow relative stenosis [IWOS]).17 In the FAME study,1,18 more than one-third of to the territory supplied are important in determining focal hemo- lesions with an angiographic 50% to 70% angiographic diameter dynamic responses to hyperemia and might explain the discrep- stenosis demonstrated an FFR of 0.80 or less whereas one-fifth of le- ancy between the epicardial luminal narrowing and FFR-based physi- sions with a 71% to 90% angiographic diameter stenosis demon- ologic significance of the lesion in many cases.21,22 Regardless of the stratedanFFRgreaterthan0.80(SWOI)(Figure1A).Inaseparatepro- causes, angiography is recognized as a suboptimal method to spective study of 1000 patients with 1129 coronary lesions,15 more assess the ischemic potential of an epicardial coronary stenosis. than one-half of lesions with greater than 50% angiographic diam- eter stenosis had an FFR greater than 0.80, whereas 1 in 7 lesions with less than 50% angiographic diameter stenosis had an FFR of 0.80 or Plaque Morphology and FFR less (IWOS) (Figure 1B). Among lesions with 50% to 70% luminal ste- nosis,approximatelyhalfhadanFFRof0.80orless,whereastheother Although the factors discussed above explain IWOS and SWOI in half had a normal FFR and no lesion-specific ischemia. These obser- some cases, they do not explain the discrepancy in many others. Re-
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