Prognostic Value of Coronary CT Angiography-Derived Fractional Flow Reserve in Non-obstructive Coronary Artery Disease: A Prospective Multicenter Observational Study

Fan Zhou, Qian Chen, Xiao Luo, Wei Cao, Ziwen Li, Bo Zhang, U Joseph Schoepf, Callum E Gill, Lili Guo, Hong Gao, Qingyao Li, Yibing Shi, Tingting Tang, Xiaochen Liu, Honglin Wu, Dongqing Wang, Feng Xu, Dongsheng Jin, Sheng Huang, Haige Li, Changjie Pan, Hongmei Gu, Lixiang Xie, Ximing Wang, Jing Ye, Jianwei Jiang, Hanqing Zhao, Xiangming Fang, Yi Xu, Wei Xing, Xiaohu Li, Xindao Yin, Guang Ming Lu, Long Jiang Zhang, Fan Zhou, Qian Chen, Xiao Luo, Wei Cao, Ziwen Li, Bo Zhang, U Joseph Schoepf, Callum E Gill, Lili Guo, Hong Gao, Qingyao Li, Yibing Shi, Tingting Tang, Xiaochen Liu, Honglin Wu, Dongqing Wang, Feng Xu, Dongsheng Jin, Sheng Huang, Haige Li, Changjie Pan, Hongmei Gu, Lixiang Xie, Ximing Wang, Jing Ye, Jianwei Jiang, Hanqing Zhao, Xiangming Fang, Yi Xu, Wei Xing, Xiaohu Li, Xindao Yin, Guang Ming Lu, Long Jiang Zhang

Abstract

Coronary artery disease (CAD) is a major contributor to morbidity and mortality worldwide. Myocardial ischemia may occur in patients with normal or non-obstructive CAD on invasive coronary angiography (ICA). The comprehensive evaluation of coronary CT angiography (CCTA) integrated with fractional flow reserve derived from CCTA (CT-FFR) to CAD may be essential to improve the outcomes of patients with non-obstructive CAD. China CT-FFR Study-2 (ChiCTR2000031410) is a large-scale prospective, observational study in 29 medical centers in China. The primary purpose is to uncover the relationship between the CCTA findings (including CT-FFR) and the outcome of patients with non-obstructive CAD. At least 10,000 patients with non-obstructive CAD but without previous revascularization will be enrolled. A 5-year follow-up will be performed. The primary endpoint is the occurrence of major adverse cardiovascular events (MACE), including all-cause mortality, non-fatal myocardial infarct, unplanned revascularization, and hospitalization for unstable angina. Clinical characteristics, laboratory and imaging examination results will be collected to analyze their prognostic value.

Keywords: coronary computed tomography angiography; coronary plaque assessment; fractional flow reserve; major adverse cardiovascular events; non-obstructive coronary artery disease.

Conflict of interest statement

UJS is a consultant for and/or receives research support from Bayer, Bracco, Elucid Bio, Guerbet, HeartFlow, Keya Medical, and Siemens Healthineers. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Zhou, Chen, Luo, Cao, Li, Zhang, Schoepf, Gill, Guo, Gao, Li, Shi, Tang, Liu, Wu, Wang, Xu, Jin, Huang, Li, Pan, Gu, Xie, Wang, Ye, Jiang, Zhao, Fang, Xu, Xing, Li, Yin, Lu and Zhang.

Figures

Figure 1
Figure 1
Patient enrollment flow chart. CCTA, coronary computed tomography angiography; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting.

References

    1. Zhao D, Liu J, Wang M, Zhang X, Zhou M. Epidemiology of cardiovascular disease in China: current features and implications. Nat Rev Cardiol. (2019) 16:203–12. 10.1038/s41569-018-0119-4
    1. Yang G, Wang Y, Zeng Y, Gao GF, Liang X, Zhou M, et al. . Rapid health transition in China, 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet. (2013) 381:1987–2015. 10.1016/S0140-6736(13)61097-1
    1. Zhou M, Wang H, Zhu J, Chen W, Wang L, Liu S, et al. . Cause-specific mortality for 240 causes in China during 1990-2013: a systematic subnational analysis for the Global Burden of Disease Study 2013. Lancet. (2016) 387:251–72. 10.1016/S0140-6736(15)00551-6
    1. Arbab-Zadeh A, Fuster V. From detecting the vulnerable plaque to managing the vulnerable patient: JACC State-of-the-Art Review. J Am Coll Cardiol. (2019) 74:1582–93. 10.1016/j.jacc.2019.07.062
    1. Muhlestein JB, Lappé DL, Lima JA, Rosen BD, May HT, Knight S, et al. . Effect of screening for coronary artery disease using CT angiography on mortality and cardiac events in high-risk patients with diabetes: the FACTOR-64 randomized clinical trial. JAMA. (2014) 312:2234–43. 10.1001/jama.2014.15825
    1. Fishbein MC, Siegel RJ. How big are coronary atherosclerotic plaques that rupture? Circulation. (1996) 94:2662–6. 10.1161/01.CIR.94.10.2662
    1. Planer D, Mehran R, Ohman EM, White HD, Newman JD, Xu K, et al. . Prognosis of patients with non-ST-segment-elevation myocardial infarction and nonobstructive coronary artery disease: propensity-matched analysis from the Acute Catheterization and Urgent Intervention Triage Strategy trial. Circ Cardiovasc Interv. (2014) 7:285–93. 10.1161/CIRCINTERVENTIONS.113.000606
    1. Emami H, Takx RAP, Mayrhofer T, Janjua S, Park J, Pursnani A, et al. . Nonobstructive coronary artery disease by coronary CT angiography improves risk stratification and allocation of statin therapy. JACC Cardiovasc Imaging. (2017) 10:1031–8. 10.1016/j.jcmg.2016.10.022
    1. Maddox TM, Stanislawski MA, Grunwald GK, Bradley SM, Ho PM, Tsai TT, et al. . Nonobstructive coronary artery disease and risk of myocardial infarction. JAMA. (2014) 312:1754–63. 10.1001/jama.2014.14681
    1. Ferencik M, Mayrhofer T, Bittner DO, Emami H, Puchner SB, Lu MT, et al. . Use of high-risk coronary atherosclerotic plaque detection for risk stratification of patients with stable chest pain: a secondary analysis of the PROMISE randomized clinical trial. JAMA Cardiol. (2018) 3:144–52. 10.1001/jamacardio.2017.4973
    1. Miller JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, et al. . Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med. (2008) 359:2324–36. 10.1056/NEJMoa0806576
    1. Marwan M, Taher MA, El Meniawy K, Awadallah H, Pflederer T, Schuhbäck A, et al. . In vivo CT detection of lipid-rich coronary artery atherosclerotic plaques using quantitative histogram analysis: a head to head comparison with IVUS. Atherosclerosis. (2011) 215:110–5. 10.1016/j.atherosclerosis.2010.12.006
    1. Bittner DO, Mayrhofer T, Budoff M, Szilveszter B, Foldyna B, Hallett TR, et al. . Prognostic value of coronary CTA in stable chest pain: CAD-RADS, CAC, and cardiovascular events in PROMISE. JACC Cardiovasc Imaging. (2020) 13:1534–45. 10.1016/j.jcmg.2019.09.012
    1. Ciccarelli G, Barbato E, Toth GG, Gahl B, Xaplanteris P, Fournier S, et al. . Angiography versus hemodynamics to predict the natural history of coronary stenoses: fractional flow reserve versus angiography in multivessel evaluation 2 substudy. Circulation. (2018) 137:1475–85. 10.1161/CIRCULATIONAHA.117.028782
    1. Imai S, Kondo T, Stone GW, Kawase Y, Ahmadi AA, Narula J, et al. . Abnormal fractional flow reserve in nonobstructive coronary artery disease. Circ Cardiovasc Interv. (2019) 12:e006961. 10.1161/CIRCINTERVENTIONS.118.006961
    1. Driessen RS, Danad I, Stuijfzand WJ, Raijmakers PG, Schumacher SP, van Diemen PA, et al. . Comparison of coronary computed tomography angiography, fractional flow reserve, and perfusion imaging for ischemia diagnosis. J Am Coll Cardiol. (2019) 73:161–73. 10.1016/j.jacc.2018.10.056
    1. Douglas PS, De Bruyne B, Pontone G, Patel MR, Norgaard BL, Byrne RA, et al. . 1-year outcomes of FFRCT-guided care in patients with suspected coronary disease: the PLATFORM study. J Am Coll Cardiol. (2016) 68:435–45. 10.1016/j.jacc.2016.05.057
    1. Patel MR, Nørgaard BL, Fairbairn TA, Nieman K, Akasaka T, Berman DS, et al. . 1-Year impact on medical practice and clinical outcomes of FFRCT: the ADVANCE registry. JACC Cardiovasc Imaging. (2020) 13:97–105. 10.1016/j.jcmg.2019.03.003
    1. Sharaf B, Wood T, Shaw L, Johnson BD, Kelsey S, Anderson RD, et al. . Adverse outcomes among women presenting with signs and symptoms of ischemia and no obstructive coronary artery disease: findings from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) angiographic core laboratory. Am Heart J. (2013) 166:134–41. 10.1016/j.ahj.2013.04.002
    1. Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al. . 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. (2020) 41:407–77. 10.1093/eurheartj/ehz425
    1. D'Agostino RB Sr, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. . General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. (2008) 117:743–53. 10.1161/CIRCULATIONAHA.107.699579
    1. McClelland RL, Jorgensen NW, Budoff M, Blaha MJ, Post WS, Kronmal RA, et al. . 10-Year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors: derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) study and the DHS (Dallas Heart Study). J Am Coll Cardiol. (2015) 66:1643–53. 10.1016/j.jacc.2015.08.035
    1. Zhang LJ, Wang Y, Schoepf UJ, Meinel FG, Bayer RR, 2nd, Qi L, et al. . Image quality, radiation dose, and diagnostic accuracy of prospectively ECG-triggered high-pitch coronary CT angiography at 70 kVp in a clinical setting: comparison with invasive coronary angiography. Eur Radiol. (2016) 26:797–806. 10.1007/s00330-015-3868-z
    1. Sand NPR, Veien KT, Nielsen SS, Nørgaard BL, Larsen P, Johansen A, et al. . Prospective comparison of FFR derived from coronary CT angiography with SPECT perfusion imaging in stable coronary artery disease: the ReASSESS study. JACC Cardiovasc Imaging. (2018) 11:1640–50. 10.1016/j.jcmg.2018.05.004
    1. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. (1990) 15:827–32. 10.1016/0735-1097(90)90282-T
    1. Hecht HS, Blaha MJ, Kazerooni EA, Cury RC, Budoff M, Leipsic J, et al. . CAC-DRS: coronary Artery Calcium Data and Reporting System. An expert consensus document of the Society of Cardiovascular Computed Tomography (SCCT). J Cardiovasc Comput Tomogr. (2018) 12:185–91. 10.1016/j.jcct.2018.03.008
    1. Sekimoto T, Akutsu Y, Hamazaki Y, Sakai K, Kosaki R, Yokota H, et al. . Regional calcified plaque score evaluated by multidetector computed tomography for predicting the addition of rotational atherectomy during percutaneous coronary intervention. J Cardiovasc Comput Tomogr. (2016) 10:221–8. 10.1016/j.jcct.2016.01.004
    1. van Rosendael AR, Narula J, Lin FY, van den Hoogen IJ, Gianni U, Al Hussein Alawamlh O, et al. . Association of high-density calcified 1K plaque with risk of acute coronary syndrome. JAMA Cardiol. (2020) 5:282–90. 10.1001/jamacardio.2019.5315
    1. van Rosendael AR, Shaw LJ, Xie JX, Dimitriu-Leen AC, Smit JM, Scholte AJ, et al. . Superior risk stratification with coronary computed tomography angiography using a comprehensive atherosclerotic risk score. JACC Cardiovasc Imaging. (2019) 12:1987–97. 10.1016/j.jcmg.2018.10.024
    1. Milletari F, Navab N, Ahmadi S.. V-Net: Fully Convolutional Neural Networks for Volumetric Medical Image Segmentation. In: 2016 Fourth International Conference on 3D Vision (3DV). Stanford, CA: (2016). p. 565–71.
    1. Hicks KA, Tcheng JE, Bozkurt B, Chaitman BR, Cutlip DE, Farb A, et al. . 2014 ACC/AHA Key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American College of Cardiology/American Heart Association task force on clinical data standards (writing committee to develop cardiovascular endpoints data Standards). J Am Coll Cardiol. (2015) 66:403–69. 10.1016/j.jacc.2014.12.018
    1. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. . Fourth universal definition of myocardial infarction (2018). Circulation. (2018) 138:e618–51. 10.1161/CIR.0000000000000617
    1. Dreyer RP, Tavella R, Curtis JP, Wang Y, Pauspathy S, Messenger J, et al. . Myocardial infarction with non-obstructive coronary arteries as compared with myocardial infarction and obstructive coronary disease: outcomes in a Medicare population. Eur Heart J. (2020) 41:870–8. 10.1093/eurheartj/ehz403
    1. Curzen N, Nicholas Z, Stuart B, Wilding S, Hill K, Shambrook J, et al. . Fractional flow reserve derived from computed tomography coronary angiography in the assessment and management of stable chest pain: the FORECAST randomized trial. Eur Heart J. (2021) 42:3844–52. 10.1093/eurheartj/ehab444
    1. Kimura T, Shiomi H, Kuribayashi S, Takaaki I, Susumu K, Hiroshi I, et al. . Cost analysis of non-invasive fractional flow reserve derived from coronary computed tomographic angiography in Japan. Cardiovasc Interv Ther. (2015) 30:38–44. 10.1007/s12928-014-0285-1
    1. Chinnaiyan KM, Safian RD, Gallagher ML, George J, Dixon SR, Bilolikar AN, et al. . Clinical use of CT-derived fractional flow reserve in the emergency department. JACC Cardiovasc Imaging. (2020) 13:452–61. 10.1016/j.jcmg.2019.05.025
    1. Antoniades C, West HW. Coronary CT angiography as an “one-stop shop” to detect the high-risk plaque and the vulnerable patient. Eur Heart J. (2021) 42:3853–5. 10.1093/eurheartj/ehab538
    1. Nørgaard BL, Leipsic J, Gaur S, Seneviratne S, Ko BS, Ito H, 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) 63:1145–55. 10.1016/j.jacc.2013.11.043
    1. Finck T, Hardenberg J, Will A, Hendrich E, Haller B, Martinoff S, et al. . 10-year follow-up after coronary computed tomography angiography in patients with suspected coronary artery disease. JACC Cardiovasc Imaging. (2019) 12:1330–8. 10.1016/j.jcmg.2018.07.020

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