Advanced computed tomographic anatomical and ...

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ARTICLE IN PRESS European Journal of Radiology xxx (2013) xxx–xxx

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European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad

Advanced computed tomographic anatomical and morphometric plaque analysis for prediction of fractional flow reserve in intermediate coronary lesions Maksymilian P. Opolski a,∗ , Cezary Kepka b , Stephan Achenbach c , Jerzy Pregowski a , Mariusz Kruk b , Adam D. Staruch d , Jacek Kadziela a , Witold Ruzyllo b , Adam Witkowski a a

Department of Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland Department of Coronary and Structural Heart Diseases, Institute of Cardiology, Warsaw, Poland c Department of Internal Medicine 2 (Cardiology), University of Erlangen, Erlangen, Germany d Medical University of Warsaw, Warsaw, Poland b

a r t i c l e

i n f o

Article history: Received 16 May 2013 Received in revised form 5 August 2013 Accepted 6 October 2013 Keywords: Coronary computed tomography angiography Fractional flow reserve Intermediate coronary stenosis

a b s t r a c t Objective: To determine the application of advanced coronary computed tomography angiography (CCTA) plaque analysis for predicting invasive fractional flow reserve (FFR) in intermediate coronary lesions. Methods: Sixty-one patients with 71 single intermediate coronary lesions (≥50–80% stenosis) on CCTA prospectively underwent coronary angiography and FFR. Advanced anatomical and morphometric plaque analysis was performed based on CCTA data set to determine optimal criteria for significant flow impairment. A significant stenosis was defined as FFR ≤ 0.80. Results: FFR averaged 0.85 ± 0.09, and 19 lesions (27%) were functionally significant. FFR correlated with minimum lumen area (MLA) (r = 0.456, p < 0.001), minimum lumen diameter (MLD) (r = 0.326, p = 0.006), reference lumen diameter (RLD) (r = 0.245, p = 0.039), plaque burden (r = −0.313, p = 0.008), lumen area stenosis (r = −0.305, p = 0.01), lesion length (r = −0.692, p < 0.001), and plaque volume (r = −0.668, p < 0.001). There was no relationship between FFR and CCTA morphometric plaque parameters. By multivariate analysis the independent predictors of FFR were lesion length (beta = −0.581, p < 0.001), MLA (beta = 0.360, p = 0.041), and RLD (beta = −0.255, p = 0.036). The optimal cutoffs for lesion length, MLA, MLD, RLD, and lumen area stenosis were >18.5 mm, ≤3.0 mm2 , ≤2.1 mm, ≤3.2 mm, and >69%, respectively (max. sensitivity: 100% for MLA, max. specificity: 79% for lumen area stenosis). Conclusions: CCTA predictors for FFR support the mathematical relationship between stenosis pressure drop and coronary flow. CCTA could prove to be a useful rule-out test for significant hemodynamic effects of intermediate coronary stenoses. Crown Copyright © 2013 Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction Fractional flow reserve (FFR) is an established method for invasive evaluation of the functional significance of coronary stenosis allowing for improved clinical decision-making as compared to two-dimensional invasive coronary angiography (ICA) [1]. However, FFR measurement involves endovascular instrumentation,

∗ Corresponding author at: Department of Interventional Cardiology and Angiology, Institute of Cardiology, Alpejska 42, 04-628 Warsaw, Poland. Tel.: +48 501 444 303; fax: +48 22 343 4506. E-mail addresses: [email protected] (M.P. Opolski), [email protected] (C. Kepka), [email protected] (S. Achenbach), [email protected] (J. Pregowski), [email protected] (M. Kruk), [email protected] (A.D. Staruch), [email protected] (J. Kadziela), [email protected] (W. Ruzyllo), [email protected] (A. Witkowski).

adds expense to the diagnostic procedure and is not performed routinely in many centers. Whereas coronary computed tomography angiography (CCTA) has emerged as a widespread noninvasive test to rule out or identify significant luminal coronary obstruction [2], it still has an unfavorable diagnostic performance for identification of lesionspecific ischemia in comparison to functional tests [3,4]. Until now, there is very limited data on the potential use of advanced plaque quantification to depict the functional significance of intermediate coronary stenoses as assessed by prospective CCTA inclusion criteria. The aims of our study were, therefore, to (1) investigate the relationship between CCTA-derived anatomical and morphometric plaque characteristics and FFR, and to (2) assess whether CCTA measurements can predict the functional significance of intermediate coronary lesions.

0720-048X/$ – see front matter. Crown Copyright © 2013 Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejrad.2013.10.005

Please cite this article in press as: Opolski MP, et al. Advanced computed tomographic anatomical and morphometric plaque analysis for prediction of fractional flow reserve in intermediate coronary lesions. Eur J Radiol (2013), http://dx.doi.org/10.1016/j.ejrad.2013.10.005


ARTICLE IN PRESS M.P. Opolski et al. / European Journal of Radiology xxx (2013) xxx–xxx

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2. Materials and methods 2.1. Study design and population Between January 2010 and October 2012, 61 stable patients with 71 single coronary artery lesions of intermediate severity (≥50–80% stenosis) in major coronary arteries as judged by visual assessment in CCTA were prospectively included in the study and scheduled for ICA with FFR in the Institute of Cardiology in Warsaw. CCTA was performed within 4 weeks preceding the ICA. Exclusion criteria were multiple stenoses within a target vessel, target vessel of 1 cross-sectional image and/or calcium content ≥70% of total plaque volume in CCTA) precluding reliable plaque evaluation [5,6], left main coronary disease (defined as ≥50% luminal narrowing by visual assessment on CCTA), prior percutaneous coronary intervention at the target vessel, prior Q-wave myocardial infarction in the coronary territory, previous coronary bypass grafting, hemodynamic instability, and renal insufficiency. The study was approved by local ethics committee and conducted in accordance with the Declaration of Helsinki. All patients provided written informed consent. 2.2. CCTA imaging and data analysis Image acquisition was performed using a dual-source CT scanner (Somatom Definition, Siemens Healthcare, Forchheim, Germany), with a beam collimation of 64 × 0.6 mm, a gantry rotation time of 330 ms, a tube voltage of 100–120 kV, a tube current of 330–438 mAs/rotation, and a pitch of 0.2–0.3. Unless contraindicated, intravenous metoprolol (sequential doses of 2.5 mg) was administered to target a heart rate 18.5 mm (89% sensitivity, 71% specificity, AUC = 0.858, 95% CI: 0.755–0.930, p < 0.001), MLD ≤ 2.1 mm (84% sensitivity, 52% specificity, AUC = 0.688, 95% CI: 0.567–0.793, p = 0.006), RLD ≤ 3.2 mm (74% sensitivity, 67% specificity, AUC = 0.654, 95% CI: 0.532–0.763, p = 0.042), lumen area stenosis >69% (58% sensitivity, 79% specificity, AUC = 0.674, 95% CI: 0.552–0.780, p = 0.032), and plaque volume >150 mm3 (89% sensitivity, 79% specificity, AUC = 0.856, 95% CI: 0.753–0.928, p < 0.001) also predicted FFR ≤ 0.80 (Fig. 3). Using the ≥50% cut-off value for angiographic diameter stenosis the sensitivity, specificity, positive and negative predictive values were 53, 88, 63 and 84%, respectively.

4. Discussion The present study demonstrates that although the CCTA-derived triad of lesion length, MLA, and RLD independently predicts invasively determined FFR, the moderate diagnostic specificity and positive predictive value of these anatomical plaque parameters preclude their use as a substitute for FFR in intermediate coronary lesions. In contrast, using our CCTA cut-off criteria to predict FFR, our study is the first prospective analysis to demonstrate the excellent negative predictive value of CCTA to exclude significant ischemia in the subset of lesions with ≥50% luminal narrowing. Of note, we have shown no relationship between morphometric plaque characteristics and lesion-specific FFR. The concept of correlating anatomical measurements with functional coronary stenosis has been derived from studies comparing intravascular ultrasound and optical coherence tomography with FFR [11–15]. Although the CCTA spatial and temporal resolutions are much lower than for intravascular ultrasound, there has been good correlation between vessel dimensions measured by these 2 imaging modalities [16,17]. Similar to our results, the majority of prior studies have shown significant but only moderate correlations between quantitative plaque dimensions and functional severity of coronary stenoses [11–15]. We believe that this most likely reflects the complexity and large variation of simulation of coronary flow data based on sole anatomical information that may be further biased by limited spatial resolution of CCTA. Indeed, the functional significance of a coronary stenosis is determined by numerous additional variables including myocardial mass, rheologic properties of blood, or microcirculation resistance [18]. To the best of our knowledge only 3 previous reports have compared cross-sectional anatomical information derived from 3dimensional CCTA with invasively measured FFR [19–21]. In the study of Kristensen et al., the functional severity of coronary stenosis was best predicted by lumen area stenosis and lesion length [19]. In contrast, in our study the independent predictors of FFR included lesion length, MLA, and RLD. We believe, this discrepancy should result from selection of various primary covariates in the multiple regression model analysis (in our case multicollinearity precluded inclusion of both MLA and its relative indices of lumen area stenosis) and different coronary obstruction inclusion criteria (retrospective and angiographic vs. prospective and CCTA-based in our study). Of note, only our results support the mathematical effect of reference vessel size, lesion geometry and lesion length on the pressure drop-coronary flow velocity relationship reflected by the laws of Poiseuille and Bernoulli as described by the following equation: P = f1 × Q + f2 × Q2 (where f1 and f2 are a function of stenosis geometry and rheologic properties of blood, whereas P and Q


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Fig. 1. Illustration of a functionally significant lesion with FFR ≤ 0.80. Coronary angiography visualization of the intermediate lesion in the proximal LAD (asterisk) with a significant FFR of 0.77 at maximal hyperemia (A). CCTA three-dimensional volume-rendered reconstruction with automatic tracking of LAD using SURE Plaque tool (B). Cross-sectional images of MLA and reference sites of the analyzed lesion with automatic depiction of lumen and vessel boundaries. Note that the calculated MLA was 2.4 mm2 (C). CCTA curved multiplanar reconstruction revealing long lesion in proximal LAD with plaque volume of 318 mm3 (D). CCTA: coronary computed tomography angiography; FFR: fractional flow reserve; LAD: left anterior descending coronary artery; MLA: minimum lumen area.

Fig. 2. Illustration of a functionally non-significant lesion with FFR > 0.80. Coronary angiography visualization of the intermediate lesion in the proximal LAD (asterisk) with a non-significant FFR of 0.85 at maximal hyperemia (A). CCTA three-dimensional volume-rendered reconstruction with automatic tracking of LAD (B). Cross-sectional images of MLA and reference sites of the analyzed lesion with automatic depiction of lumen and vessel boundaries. Note that the calculated MLA was 3.2 mm2 (C). CCTA curved multiplanar reconstruction revealing short lesion in proximal LAD with plaque volume of 42 mm3 (D). CCTA: coronary computed tomography angiography; FFR: fractional flow reserve; LAD: left anterior descending coronary artery; MLA: minimum lumen area.




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Table 2 Angiographic and CCTA characteristics in 71 intermediate lesions. Total (n = 71) Angiographic parameters RLD (mm) MLD (mm) Diameter stenosis (%) CCTA parameters Proximal and distal reference sites RLD (mm) Mean lumen area (mm2 ) Mean vessel area (mm2 ) Mean plaque burden (%) Proximal edge of the lesion Mean lumen diameter (mm) Lumen area (mm2 ) Vessel area (mm2 ) Plaque burden (%) MLA site MLA (mm2 ) Vessel area (mm2 ) Plaque burden (%) Lumen eccentricity index Atheroma eccentricity index MLD site MLD (mm) Lumen area (mm2 ) Vessel area (mm2 ) Plaque burden (%) Distal edge of the lesion Mean lumen diameter (mm) Lumen area (mm2 ) Vessel area (mm2 ) Plaque burden (%) Lesion measurements Lesion length (mm) Lesion tortuosity Lumen area stenosis (%) Plaque burden (%) Remodelling index (%) Fatty plaque volume (%) Fibrous plaque volume (%) Calcified plaque volume (%) Total plaque volume (mm3 ) Mean plaque attenuation (HU)

2.6 ± 0.6 1.5 ± 0.4 41 ± 11

FFR ≤ 0.80 (n = 19)

FFR > 0.80 (n = 52)

2.5 ± 0.4 1.2 ± 0.2 50 ± 9

P-value

2.6 ± 0.6 1.6 ± 0.4 38 ± 10

0.230