Clinical Relevance of Functionally Insignificant Moderate Coronary Artery Stenosis Assessed by 3-Vessel Fractional Flow Reserve Measurement

Jonghanne Park, Joo Myung Lee, Bon-Kwon Koo, Eun-Seok Shin, Chang-Wook Nam, Joon-Hyung Doh, Doyeon Hwang, Jinlong Zhang, Xinyang Hu, JianAn Wang, Fei Ye, Shaoliang Chen, Junqing Yang, Jiyan Chen, Nobuhiro Tanaka, Hiroyoshi Yokoi, Hitoshi Matsuo, Hiroaki Takashima, Yasutsugu Shiono, Takashi Akasaka, Jonghanne Park, Joo Myung Lee, Bon-Kwon Koo, Eun-Seok Shin, Chang-Wook Nam, Joon-Hyung Doh, Doyeon Hwang, Jinlong Zhang, Xinyang Hu, JianAn Wang, Fei Ye, Shaoliang Chen, Junqing Yang, Jiyan Chen, Nobuhiro Tanaka, Hiroyoshi Yokoi, Hitoshi Matsuo, Hiroaki Takashima, Yasutsugu Shiono, Takashi Akasaka

Abstract

Background: Understanding of the risk conferred by functionally insignificant lesions in multiple coronary vessels is limited. We investigated the prognostic implications of coronary artery disease (CAD) based on 3-vessel fractional flow reserve (FFR).

Methods and results: A total of 1,136 patients underwent FFR measurement in the 3 major epicardial arteries. We defined vessels with "Moderate CAD" as vessels with FFR, 0.81 to 0.87. Patients were classified into Group 1: No apparent CAD (FFR>0.87 in all 3-vessels); Group 2: Single-vessel moderate CAD; Group 3: Multivessel moderate CAD; and Group 4: Functionally significant CAD (FFR≤0.80) in any vessel. The primary end point was 2-year major adverse cardiac events, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. Forty-three percent of patients had moderate CAD (Group 2: 403/1136, 35.5%; Group 3: 84/1136, 7.4%). The 2-year risk of major adverse cardiac events was not significantly different between patients with single-vessel moderate CAD and no apparent CAD (2.6 versus 2.6%; HR, 1.1; 95% confidence interval, 0.4%-2.8%; P=0.89). However, patients with multivessel moderate CAD were at significantly higher risk than Group 1 (7.4 versus 2.6%; hazard ratio, 3.3; 95% confidence interval, 1.1%-9.8%; P=0.03). The risk of major adverse cardiac events in patients with multivessel moderate CAD was comparable to that of patients with functionally significant CAD (hazard ratio, 1.2; 95% confidence interval, 0.5%-3.0%; P=0.67). In a multivariable regression model, multivessel moderate CAD was an independent predictor of greater risk of 2-year major adverse cardiac events.

Conclusions: Global physiologic assessment with FFR measurement of 3 vessels can identify multivessel moderate CAD. The prognostic implication of multivessel moderate CAD appears comparable to that of functionally significant CAD.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01621438.

Keywords: coronary artery disease; fractional flow reserve; multivessel coronary artery disease; physiology/function; prognosis.

© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1
Figure 1
Distribution of per‐vessel fractional flow reserve. The histogram depicts the frequency of vessels by FFR values. Among the total 3298 vessels, 12.3% were functionally significant (FFR ≤0.80, yellow bars). The functionally insignificant vessels (87.7%, 2891/3298) are further categorized into quartiles and depicted as bars filled with graded saturation (blue). The darkest blue bars represent vessels in the lowest quartile (FFR 0.81–0.87) defined as moderate CAD in this study. CAD indicates coronary artery disease; FFR, fractional flow reserve.
Figure 2
Figure 2
Distribution of SYNTAX score among the 4 patient groups. The box plots with whiskers depict distribution of SYNTAX score among the 4 patient groups including interquartile range, median, and minimum to maximum values, within 1.5 times the interquartile range. *P<0.05 for between‐group comparisons; n.s. indicates not significant; SYNTAX, synergy between percutaneous coronary intervention with taxus and cardiac surgery.
Figure 3
Figure 3
Comparison of 2‐year MACE among the 4 groups. Cumulative incidence of (MACE) in each group is shown. CAD indicates coronary artery disease; FFR, fractional flow reserve; MACE, major adverse cardiac events.
Figure 4
Figure 4
Comparison of 2‐year MACE among the 4 groups, restricted to subgroups. The clinical outcomes of 4 patient groups are compared in patient subgroups with (A) clinically high‐risk (diabetes mellitus or acute coronary syndrome) and (B) anatomically nonobstructive CAD with all coronary vessels % DS <50%. Cumulative incidences of major adverse cardiac events (MACE) patients are presented. CAD indicates coronary artery disease; DS, diameter stenosis; FFR, fractional flow reserve.

References

    1. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH, Jacobs AK, Albert N, Creager MA, Ettinger SM, Halperin JL, Hochman JS, Kushner FG, Magnus Ohman E, Stevenson W, Yancy CW. 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. Circulation. 2011;2011:124.
    1. Kolh P, Windecker S, Alfonso F, Collet J‐P, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Jüni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann F‐J, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A; European Society of Cardiology Committee for Practice Guidelines , Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol Ç, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S; EACTS Clinical Guidelines Committee , Sousa Uva M, Achenbach S, Pepper J, Anyanwu A, Badimon L, Bauersachs J, Baumbach A, Beygui F, Bonaros N, De Carlo M, Deaton C, Dobrev D, Dunning J, Eeckhout E, Gielen S, Hasdai D, Kirchhof P, Luckraz H, Mahrholdt H, Montalescot G, Paparella D, Rastan AJ, Sanmartin M, Sergeant P, Silber S, Tamargo J, ten Berg J, Thiele H, van Geuns R‐J, Wagner H‐O, Wassmann S, Wendler O, Zamorano JL; Task Force on Myocardial Revascularization of the European Society of Cardiology and the European Association for Cardio‐Thoracic Surgery, European Association of Percutaneous Cardiovascular Interventions . 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 J Cardiothorac Surg. 2014;46:517–592.
    1. De Bruyne B, Fearon WF, Pijls NHJ, Barbato E, Tonino P, Piroth Z, Jagic N, Mobius‐Winckler S, Rioufol G, Witt N, Kala P, MacCarthy P, Engström T, Oldroyd K, Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Limacher A, Nüesch E, Jüni P; FAME 2 Trial Investigators . Fractional flow reserve‐guided PCI for stable coronary artery disease. N Engl J Med. 2014;371:1208–1217.
    1. Pijls NHJ, Fearon WF, Tonino PAL, Siebert U, Ikeno F, Bornschein B, van't Veer M, Klauss V, Manoharan G, Engstrøm T, Oldroyd KG, Ver Lee PN, MacCarthy PA, De Bruyne B. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease. J Am Coll Cardiol. 2010;56:177–184.
    1. Shaw LJ, Berman DS, Maron DJ, Mancini GBJ, Hayes SW, Hartigan PM, Weintraub WS, O'Rourke RA, Dada M, Spertus JA, Chaitman BR, Friedman J, Slomka P, Heller GV, Germano G, Gosselin G, Berger P, Kostuk WJ, Schwartz RG, Knudtson M, Veledar E, Bates ER, McCallister B, Teo KK, Boden WE; COURAGE Investigators . Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation. 2008;117:1283–1291.
    1. Jiménez‐Navarro M, Alonso‐Briales JH, Hernández García MJ, Rodríguez Bailón I, Gómez‐Doblas JJ, de Teresa Galván E. Measurement of fractional flow reserve to assess moderately severe coronary lesions: correlation with dobutamine stress echocardiography. J Interv Cardiol. 2001;14:499–504.
    1. Lee JM, Jung J‐H, Hwang D, Park J, Fan Y, Na S‐H, Doh J‐H, Nam C‐W, Shin E‐S, Koo B‐K. Coronary flow reserve and microcirculatory resistance in patients with intermediate coronary stenosis. J Am Coll Cardiol. 2016;67:1158–1169.
    1. Adjedj J, De Bruyne B, Floré V, Di Gioia G, Ferrara A, Pellicano M, Toth GG, Bartunek J, Vanderheyden M, Heyndrickx GR, Wijns W, Barbato E. Significance of intermediate values of fractional flow reserve in patients with coronary artery disease. Circulation. 2016;133:502–508.
    1. Maddox TM, Stanislawski MA, Grunwald GK, Bradley SM, Ho PM, Tsai TT, Patel MR, Sandhu A, Valle J, Magid DJ, Leon B, Bhatt DL, Fihn SD, Rumsfeld JS. Nonobstructive coronary artery disease and risk of myocardial infarction. JAMA. 2014;312:1754–1763.
    1. LaMonte MJ, FitzGerald SJ, Church TS, Barlow CE, Radford NB, Levine BD, Pippin JJ, Gibbons LW, Blair SN, Nichaman MZ. Coronary artery calcium score and coronary heart disease events in a large cohort of asymptomatic men and women. Am J Epidemiol. 2005;162:421–429.
    1. Lee JM, Koo B‐K, Shin E‐S, Nam C‐W, Doh J‐H, Hwang D, Park J, Kim K‐J, Zhang J, Hu X, Wang J, Ahn C, Ye F, Chen S, Yang J, Chen J, Tanaka N, Yokoi H, Matsuo H, Takashima H, Shiono Y, Akasaka T. Clinical implications of three‐vessel fractional flow reserve measurement in patients with coronary artery disease. Eur Heart J. Available at: . Accessed February 10, 2018.
    1. Sianos G, Morel M‐A, Kappetein AP, Morice M‐C, Colombo A, Dawkins K, van den Brand M, Van Dyck N, Russell ME, Mohr FW, Serruys PW. The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention. 2005;1:219–227.
    1. Yadav M, Palmerini T, Caixeta A, Madhavan MV, Sanidas E, Kirtane AJ, Stone GW, Généreux P. Prediction of coronary risk by SYNTAX and derived scores: synergy between percutaneous coronary intervention with taxus and cardiac surgery. J Am Coll Cardiol. 2013;62:1219–1230.
    1. Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es G‐A, Steg PG, Morel M, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW; Academic Research Consortium . Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007;115:2344–2351.
    1. Barbato E, Toth GG, Johnson NP, Pijls NHJ, Fearon WF, Tonino PAL, Curzen N, Piroth Z, Rioufol G, Jüni P, De Bruyne B. A prospective natural history study of coronary atherosclerosis using fractional flow reserve. J Am Coll Cardiol. 2016;68:2247–2255.
    1. Cutlip DE, Chhabra AG, Baim DS, Chauhan MS, Marulkar S, Massaro J, Bakhai A, Cohen DJ, Kuntz RE, Ho KKL. Beyond restenosis: five‐year clinical outcomes from second‐generation coronary stent trials. Circulation. 2004;110:1226–1230.
    1. Glaser R, Selzer F, Faxon DP, Laskey WK, Cohen HA, Slater J, Detre KM, Wilensky RL. Clinical progression of incidental, asymptomatic lesions discovered during culprit vessel coronary intervention. Circulation. 2005;111:143–149.
    1. Zellweger MJ, Kaiser C, Jeger R, Brunner‐La Rocca H‐P, Buser P, Bader F, Mueller‐Brand J, Pfisterer M. Coronary artery disease progression late after successful stent implantation. J Am Coll Cardiol. 2012;59:793–799.
    1. Arbab‐Zadeh A, Fuster V. The risk continuum of atherosclerosis and its implications for defining CHD by coronary angiography. J Am Coll Cardiol. 2016;68:2467–2478.
    1. Jespersen L, Hvelplund A, Abildstrøm SZ, Pedersen F, Galatius S, Madsen JK, Jørgensen E, Kelbæk H, Prescott E. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012;33:734–744.
    1. Mushtaq S, De Araujo Gonçalves P, Garcia‐Garcia HM, Pontone G, Bartorelli AL, Bertella E, Campos CM, Pepi M, Serruys PW, Andreini D. Long‐term prognostic effect of coronary atherosclerotic burden: validation of the computed tomography‐Leaman score. Circ Cardiovasc Imaging. 2015;8:e002332.
    1. Chow BJW, Small G, Yam Y, Chen L, McPherson R, Achenbach S, Al‐Mallah M, Berman DS, Budoff MJ, Cademartiri F, Callister TQ, Chang H‐J, Cheng VY, Chinnaiyan K, Cury R, Delago A, Dunning A, Feuchtner G, Hadamitzky M, Hausleiter J, Karlsberg RP, Kaufmann PA, Kim Y‐J, Leipsic J, LaBounty T, Lin F, Maffei E, Raff GL, Shaw LJ, Villines TC, Min JK; CONFIRM Investigators . Prognostic and therapeutic implications of statin and aspirin therapy in individuals with nonobstructive coronary artery disease: results from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry). Arterioscler Thromb Vasc Biol. 2015;35:981–989.

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