Research Article|Articles in Press

Long-term prognostic implications of hemodynamic and plaque assessment using coronary CT angiography


      • FFRCT and PAV were independent predictors of 10-year target vessel failure.
      • WSS, ΔFFRCT, and LAPV were independent predictors of 10-year target lesion failure.
      • Plaque and hemodynamic predictors have additive predictability for 10-year outcome.


      Background and aims

      Hemodynamic and plaque characteristics can be analyzed using coronary CT angiography (CTA). We aimed to explore long-term prognostic implications of hemodynamic and plaque characteristics using coronary CT angiography (CTA).


      Invasive fractional flow reserve (FFR) and CTA-derived FFR (FFRCT) were undertaken for 136 lesions in 78 vessels and followed-up to 10 years until December 2020. FFRCT, wall shear stress (WSS), change in FFRCT across the lesion (ΔFFRCT), total plaque volume (TPV), percent atheroma volume (PAV), and low-attenuation plaque volume (LAPV) for target lesions [L] and vessels [V] were obtained by independent core laboratories. Their collective influence was evaluated for the clinical endpoints of target vessel failure (TVF) and target lesion failure (TLF).


      During a median follow-up of 10.1 years, PAV[V] (per 10% increase, HR 2.32 [95% CI 1.11–4.86], p = 0.025), and FFRCT[V] (per 0.1 increase, HR 0.56 [95% CI 0.37–0.84], p = 0.006) were independent predictors of TVF for the per-vessel analysis, and WSS[L] (per 100 dyne/cm2 increase, HR 1.43 [1.09–1.88], p = 0.010), LAPV[L] (per 10 mm3 increase, HR 3.81 [1.16–12.5], p = 0.028), and ΔFFRCT[L] (per 0.1 increase, HR 1.39 [1.02–1.90], p = 0.040) were independent predictors of TLF for the per-lesion analysis after adjustment for clinical and lesion characteristics. The addition of both plaque and hemodynamic predictors improved the predictability for 10-year TVF and TLF of clinical and lesion characteristics (all p < 0.05).


      Vessel- and lesion-level hemodynamic characteristics, and vessel-level plaque quantity, and lesion-level plaque compositional characteristics assessed by CTA offer independent and additive long-term prognostic value.

      Graphical abstract


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        • Investigators S.-H.
        • Newby D.E.
        • Adamson P.D.
        • et al.
        Coronary ct angiography and 5-year risk of myocardial infarction.
        N. Engl. J. Med. 2018; 379: 924-933
        • Group D.T.
        • Maurovich-Horvat P.
        • Bosserdt M.
        • et al.
        CT or Invasive coronary angiography in stable chest pain.
        N. Engl. J. Med. 2022; 386: 1591-1602
        • Nielsen L.H.
        • Botker H.E.
        • Sorensen H.T.
        • et al.
        Prognostic assessment of stable coronary artery disease as determined by coronary computed tomography angiography: a Danish multicentre cohort study.
        Eur. Heart J. 2017; 38: 413-421
        • 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
        • 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
        • Kumar A.
        • Thompson E.W.
        • Lefieux A.
        • et al.
        High coronary shear stress in patients with coronary artery disease predicts myocardial infarction.
        J. Am. Coll. Cardiol. 2018; 72: 1926-1935
        • Yang S.
        • Choi G.
        • Zhang J.
        • et al.
        Association among local hemodynamic parameters derived from CT angiography and their comparable implications in development of acute coronary syndrome.
        Front. Cardiovasc. Med. 2021; 8713835
        • Chang H.J.
        • Lin F.Y.
        • Lee S.E.
        • et al.
        Coronary atherosclerotic precursors of acute coronary syndromes.
        J. Am. Coll. Cardiol. 2018; 71: 2511-2522
        • Williams M.C.
        • Kwiecinski J.
        • Doris M.
        • et al.
        Low-attenuation noncalcified plaque on coronary computed tomography angiography predicts myocardial infarction: results from the multicenter SCOT-HEART Trial (Scottish Computed Tomography of the HEART).
        Circulation. 2020; 141: 1452-1462
        • Andreini D.
        • Magnoni M.
        • Conte E.
        • et al.
        Coronary plaque features on CTA can identify patients at increased risk of cardiovascular events.
        JACC Cardiovasc. Imag. 2020; 13: 1704-1717
        • Yang S.
        • Lee J.M.
        • Hoshino M.
        • et al.
        Prognostic implications of comprehensive whole vessel plaque quantification using coronary computed tomography angiography.
        JACC (J. Am. Coll. Cardiol.): Asia. 2021; 1: 37-48
        • Taylor A.J.
        • Cerqueira M.
        • Hodgson J.M.
        • et al.
        ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography. A report of the American college of cardiology foundation appropriate use criteria task force, the society of cardiovascular computed tomography, the American college of radiology, the American heart association, the American society of echocardiography, the American society of nuclear cardiology, the North American society for cardiovascular imaging, the society for cardiovascular angiography and interventions, and the society for cardiovascular magnetic resonance.
        J. Cardiovasc. Comput. Tomogr. 2010; 4 (407 e1-33)
        • Vignon-Clementel I.E.
        • Figueroa C.A.
        • Jansen K.E.
        • Taylor C.A.
        Outflow boundary conditions for 3D simulations of non-periodic blood flow and pressure fields in deformable arteries.
        Comput. Methods Biomech. Biomed. Eng. 2010; 13: 625-640
        • 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
        • Lee J.M.
        • Choi G.
        • Koo B.K.
        • et al.
        Identification of high-risk plaques destined to cause acute coronary syndrome using coronary computed tomographic angiography and computational fluid dynamics.
        JACC Cardiovasc. Imag. 2019; 12: 1032-1043
        • Park J.B.
        • Choi G.
        • Chun E.J.
        • et al.
        Computational fluid dynamic measures of wall shear stress are related to coronary lesion characteristics.
        Heart. 2016; 102: 1655-1661
        • Yang S.
        • Koo B.K.
        • Hoshino M.
        • et al.
        CT angiographic and plaque predictors of functionally significant coronary disease and outcome using machine learning.
        JACC Cardiovasc. Imag. 2021; 14: 629-641
        • Garcia-Garcia H.M.
        • McFadden E.P.
        • Farb A.
        • et al.
        Standardized end point definitions for coronary intervention trials: the Academic Research Consortium-2 consensus document.
        Circulation. 2018; 137: 2635-2650
        • Budoff M.J.
        • Young R.
        • Burke G.
        • et al.
        Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).
        Eur. Heart J. 2018; 39: 2401-2408
        • Zimmermann F.M.
        • Ferrara A.
        • Johnson N.P.
        • et al.
        Deferral vs. performance of percutaneous coronary intervention of functionally non-significant coronary stenosis: 15-year follow-up of the DEFER trial.
        Eur. Heart J. 2015; 36: 3182-3188
        • Ihdayhid A.R.
        • Norgaard B.L.
        • Gaur S.
        • et al.
        Prognostic value and risk continuum of noninvasive fractional flow reserve derived from coronary CT angiography.
        Radiology. 2019; 292: 343-351
        • Norgaard B.L.
        • Gaur S.
        • Fairbairn T.A.
        • et al.
        Prognostic value of coronary computed tomography angiographic derived fractional flow reserve: a systematic review and meta-analysis.
        Heart. 2022; 108: 194-202
        • Hell M.M.
        • Motwani M.
        • Otaki Y.
        • et al.
        Quantitative global plaque characteristics from coronary computed tomography angiography for the prediction of future cardiac mortality during long-term follow-up.
        Eur. Heart J. Cardiovasc. Imaging. 2017; 18: 1331-1339
        • Han D.
        • Kolli K.K.
        • Al'Aref S.J.
        • et al.
        Machine learning framework to identify individuals at risk of rapid progression of coronary atherosclerosis: from the PARADIGM Registry.
        J. Am. Heart Assoc. 2020; 9e013958
        • Yang S.
        • Koo B.K.
        • Hwang D.
        • et al.
        High-risk morphological and physiological coronary disease attributes as outcome markers after medical treatment and revascularization.
        JACC Cardiovasc. Imag. 2021; 14: 1977-1989
        • Schlett C.L.
        • Maurovich-Horvat P.
        • Ferencik M.
        • et al.
        Histogram analysis of lipid-core plaques in coronary computed tomographic angiography: ex vivo validation against histology.
        Invest. Radiol. 2013; 48: 646-653
        • Marwan M.
        • Taher M.A.
        • Meniawy K.E.
        • 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: 110-115
        • Kashiwagi M.
        • Tanaka A.
        • Kitabata H.
        • et al.
        Feasibility of noninvasive assessment of thin-cap fibroatheroma by multidetector computed tomography.
        JACC Cardiovasc. Imag. 2009; 2: 1412-1419
        • Tufaro V.
        • Safi H.
        • Torii R.
        • et al.
        Wall shear stress estimated by 3D-QCA can predict cardiovascular events in lesions with borderline negative fractional flow reserve.
        Atherosclerosis. 2021; 322: 24-30
        • Gijsen F.
        • Katagiri Y.
        • Barlis P.
        • et al.
        Expert recommendations on the assessment of wall shear stress in human coronary arteries: existing methodologies, technical considerations, and clinical applications.
        Eur. Heart J. 2019; 40: 3421-3433
        • Malek A.M.
        • Alper S.L.
        • Izumo S.
        Hemodynamic shear stress and its role in atherosclerosis.
        JAMA. 1999; 282: 2035-2042
        • Samady H.
        • Eshtehardi P.
        • McDaniel M.C.
        • et al.
        Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease.
        Circulation. 2011; 124: 779-788
        • Bourantas C.V.
        • Zanchin T.
        • Torii R.
        • et al.
        Shear stress estimated by quantitative coronary angiography predicts plaques prone to progress and cause events.
        JACC Cardiovasc. Imag. 2020; 13: 2206-2219
        • Yang S.
        • Koo B.K.
        • Narula J.
        Interactions between morphological plaque characteristics and coronary physiology: from pathophysiological basis to clinical implications.
        JACC Cardiovasc. Imag. 2022; 15: 1139-1151
        • Williams M.C.
        • Moss A.J.
        • Dweck M.
        • et al.
        Coronary artery plaque characteristics associated with adverse outcomes in the SCOT-HEART study.
        J. Am. Coll. Cardiol. 2019; 73: 291-301