Atherosclerotic plaque characteristics by CT angiography identify coronary lesions that cause ischemia: a direct comparison to fractional flow reserve.
Park Hyung-Bok,Heo Ran,Ó Hartaigh Bríain,Cho Iksung,Gransar Heidi,Nakazato Ryo,Leipsic Jonathon,Mancini G B John,Koo Bon-Kwon,Otake Hiromasa,Budoff Matthew J,Berman Daniel S,Erglis Andrejs,Chang Hyuk-Jae,Min James K
JACC. Cardiovascular imaging
OBJECTIVES:This study evaluated the association between atherosclerotic plaque characteristics (APCs) by coronary computed tomographic angiography (CTA), and lesion ischemia by fractional flow reserve (FFR). BACKGROUND:FFR is the gold standard for determining lesion ischemia. Although APCs by CTA-including aggregate plaque volume % (%APV), positive remodeling (PR), low attenuation plaque (LAP), and spotty calcification (SC)-are associated with future coronary syndromes, their relationship to lesion ischemia is unclear. METHODS:252 patients (17 centers, 5 countries; mean age 63 years; 71% males) underwent coronary CTA, with FFR performed for 407 coronary lesions. Coronary CTA was interpreted for <50% and ≥50% stenosis, with the latter considered obstructive. APCs by coronary CTA were defined as: 1) PR, lesion diameter/reference diameter >1.10; 2) LAP, any voxel <30 Hounsfield units; and 3) SC, nodular calcified plaque <3 mm. Odds ratios (OR) and net reclassification improvement of APCs for lesion ischemia, defined by FFR ≤0.8, were analyzed. RESULTS:By FFR, ischemia was present in 151 lesions (37%). %APV was associated with a 50% increased risk of ischemia per 5% additional APV. PR, LAP, and SC were associated with ischemia, with a 3 to 5 times higher prevalence than in nonischemic lesions. In multivariable analyses, a stepwise increased risk of ischemia was observed for 1 (OR: 4.0, p < 0.001) and ≥2 (OR: 12.1, p < 0.001) APCs. These findings were APC dependent, with PR (OR: 5.3, p < 0.001) and LAP (OR: 2.1, p = 0.038) associated with ischemia, but not SC. When examined by stenosis severity, PR remained a predictor of ischemia for all lesions, whereas %APV and LAP were associated with ischemia for only ≥50%, but not for <50%, stenosis. CONCLUSIONS:%APV and APCs by coronary CTA improve identification of coronary lesions that cause ischemia. PR is associated with all ischemia-causing lesions, whereas %APV and LAP are only associated with ischemia-causing lesions ≥50%. (Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography; NCT01233518).
Integrated prediction of lesion-specific ischaemia from quantitative coronary CT angiography using machine learning: a multicentre study.
Dey Damini,Gaur Sara,Ovrehus Kristian A,Slomka Piotr J,Betancur Julian,Goeller Markus,Hell Michaela M,Gransar Heidi,Berman Daniel S,Achenbach Stephan,Botker Hans Erik,Jensen Jesper Moller,Lassen Jens Flensted,Norgaard Bjarne Linde
OBJECTIVES:We aimed to investigate if lesion-specific ischaemia by invasive fractional flow reserve (FFR) can be predicted by an integrated machine learning (ML) ischaemia risk score from quantitative plaque measures from coronary computed tomography angiography (CTA). METHODS:In a multicentre trial of 254 patients, CTA and invasive coronary angiography were performed, with FFR in 484 vessels. CTA data sets were analysed by semi-automated software to quantify stenosis and non-calcified (NCP), low-density NCP (LD-NCP, < 30 HU), calcified and total plaque volumes, contrast density difference (CDD, maximum difference in luminal attenuation per unit area) and plaque length. ML integration included automated feature selection and model building from quantitative CTA with a boosted ensemble algorithm, and tenfold stratified cross-validation. RESULTS:Eighty patients had ischaemia by FFR (FFR ≤ 0.80) in 100 vessels. Information gain for predicting ischaemia was highest for CDD (0.172), followed by LD-NCP (0.125), NCP (0.097), and total plaque volumes (0.092). ML exhibited higher area-under-the-curve (0.84) than individual CTA measures, including stenosis (0.76), LD-NCP volume (0.77), total plaque volume (0.74) and pre-test likelihood of coronary artery disease (CAD) (0.63); p < 0.006. CONCLUSIONS:Integrated ML ischaemia risk score improved the prediction of lesion-specific ischaemia by invasive FFR, over stenosis, plaque measures and pre-test likelihood of CAD. KEY POINTS:• Integrated ischaemia risk score improved prediction of ischaemia over quantitative plaque measures • Integrated ischaemia risk score showed higher prediction of ischaemia than standard approach • Contrast density difference had the highest information gain to identify lesion-specific ischaemia.
Prognostic Implications of Plaque Characteristics and Stenosis Severity in Patients With Coronary Artery Disease.
Lee Joo Myung,Choi Ki Hong,Koo Bon-Kwon,Park Jonghanne,Kim Jihoon,Hwang Doyeon,Rhee Tae-Min,Kim Hyung Yoon,Jung Hae Won,Kim Kyung-Jin,Yoshiaki Kawase,Shin Eun-Seok,Doh Joon-Hyung,Chang Hyuk-Jae,Cho Yun-Kyeong,Yoon Hyuck-Jun,Nam Chang-Wook,Hur Seung-Ho,Wang Jianan,Chen Shaoliang,Kuramitsu Shoichi,Tanaka Nobuhiro,Matsuo Hitoshi,Akasaka Takashi
Journal of the American College of Cardiology
BACKGROUND:Although the presence of ischemia is a key prognostic factor in patients with coronary artery disease, the presence of high-risk plaque characteristics (HRPC) is also associated with increased risk of cardiovascular events. Limited data exist regarding the prognostic implications of combined information on physiological stenosis severity assessed by fractional flow reserve (FFR) and plaque vulnerability by coronary computed tomography angiography (CTA)-defined HRPC. OBJECTIVES:The current study aimed to evaluate the: 1) association between physiological stenosis severity and coronary CTA-defined HRPC; and 2) prognostic implications of coronary CTA-defined HRPC according to physiological stenosis severity in patients with coronary artery disease. METHODS:A total of 772 vessels (299 patients) evaluated by both coronary CTA and FFR were analyzed. The presence and number of HRPC (minimum lumen area <4 mm, plaque burden ≥70%, low attenuating plaque, positive remodeling, napkin-ring sign, or spotty calcification) were assessed using coronary CTA images. The risk of vessel-oriented composite outcome (VOCO) (a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death) at 5 years was compared according to the number of HRPC and FFR categories. RESULTS:The proportion of lesions with ≥3 HRPC was significantly decreased according to the increase in FFR values (58.6%, 46.5%, 36.8%, 15.7%, and 3.5% for FFR ≤0.60, 0.61 to ≤0.70, 0.71 to ≤0.80, 0.81 to ≤0.90, and >0.90, respectively; overall p value <0.001). Both FFR and number of HRPC showed significant association with the estimated risk of VOCO (p = 0.008 and p = 0.023, respectively). In the FFR >0.80 group, lesions with ≥3 HRPC showed significantly higher risk of VOCO than those with <3 HRPC (15.0% vs. 4.3%; hazard ratio: 3.964; 95% confidence interval: 1.451 to 10.828; p = 0.007). However, there was no significant difference in the risk of VOCO according to HRPC in the FFR ≤0.80 group. By multivariable analysis, the presence of ≥3 HRPC was independently associated with the risk of VOCO in the FFR >0.80 group. CONCLUSIONS:Physiological stenosis severity and the number of HRPC were closely related, and both components had significant association with the risk of clinical events. However, the prognostic implication of HRPC was different according to FFR. Integration of both physiological stenosis severity and plaque vulnerability would provide better prognostic stratification of patients than either individual component alone, especially in patients with FFR >0.80. (Clinical Implication of 3-vessel Fractional Flow Reserve [3V FFR-FRIENDS study]; NCT01621438).
The predictive factors affecting false positive in on-site operated CT-fractional flow reserve based on fluid and structural interaction.
Kawaguchi Yuko O,Fujimoto Shinichiro,Kumamaru Kanako K,Kato Etsuro,Dohi Tomotaka,Takamura Kazuhisa,Aoshima Chihiro,Kamo Yuki,Kato Yoshiteru,Hiki Makoto,Okai Iwao,Okazaki Shinya,Aoki Shigeki,Daida Hiroyuki
International journal of cardiology. Heart & vasculature
Background:A novel algorithm has been developed for the on-site analysis of CT-fractional flow reserve (CT-FFR) using fluid structural interactions. There have been no reports on the factors affecting the diagnostic performance of CT-FFR using this algorithm. We evaluated the factors predictive of false-positive CT-FFR findings compared to invasive FFR as a reference standard. Methods:The subjects were 66 consecutive cases (81 vessels) who underwent invasive FFR assessment within 90 days of the detection of 30-90% stenosis of one vessel of the major coronary artery, from among patients with suspected coronary arterial disease who underwent one-rotation scanning by 320-row coronary CT angiography (CCTA). The prospective CCTA mode was used for all patients, with the X-ray exposure set in a range of 70-99% of the RR interval. The FFR was calculated on-site from multiple cardiac phases. Factors associated with a false-positive finding of functional stenosis on CT-FFR, defined as an invasive FFR of ≤0.80, were evaluated using logistic regression analysis. Results:Thirty-nine vessels (48.1%) had an invasive FFR of ≤0.80. CT-FFR and invasive FFR values disagreed in 13 vessels in 13 patients. The values were false positive in 12 of the vessels. In an analysis of patient characteristics, the body mass index (odds ratio, 1.33; 95%CI, 1.06-1.67; p = 0.01) and Image noise (odds ratio, 1.18; 95%CI, 1.01-1.40; p = 0.04) were predictive of false-positive findings. The presence of calcified plaque (odds ratio, 5.16; 95%CI, 1.06-20.85; p = 0.01) was the only significant predictive factor in a vessel-based analysis of lesion characteristics. Conclusions:The presence of calcified plaque exerted a significant effect on the diagnostic performance of CT-FFR, and did so independently of the degree of calcification indicated by the Agatston score.
Influence of Coronary Calcium on Diagnostic Performance of Machine Learning CT-FFR: Results From MACHINE Registry.
Tesche Christian,Otani Katharina,De Cecco Carlo N,Coenen Adriaan,De Geer Jakob,Kruk Mariusz,Kim Young-Hak,Albrecht Moritz H,Baumann Stefan,Renker Matthias,Bayer Richard R,Duguay Taylor M,Litwin Sheldon E,Varga-Szemes Akos,Steinberg Daniel H,Yang Dong Hyun,Kepka Cezary,Persson Anders,Nieman Koen,Schoepf U Joseph
JACC. Cardiovascular imaging
OBJECTIVES:This study was conducted to investigate the influence of coronary artery calcium (CAC) score on the diagnostic performance of machine-learning-based coronary computed tomography (CT) angiography (cCTA)-derived fractional flow reserve (CT-FFR). BACKGROUND:CT-FFR is used reliably to detect lesion-specific ischemia. Novel CT-FFR algorithms using machine-learning artificial intelligence techniques perform fast and require less complex computational fluid dynamics. Yet, influence of CAC score on diagnostic performance of the machine-learning approach has not been investigated. METHODS:A total of 482 vessels from 314 patients (age 62.3 ± 9.3 years, 77% male) who underwent cCTA followed by invasive FFR were investigated from the MACHINE (Machine Learning based CT Angiography derived FFR: a Multi-center Registry) registry data. CAC scores were quantified using the Agatston convention. The diagnostic performance of CT-FFR to detect lesion-specific ischemia was assessed across all Agatston score categories (CAC 0, >0 to <100, 100 to <400, and ≥400) on a per-vessel level with invasive FFR as the reference standard. RESULTS:The diagnostic accuracy of CT-FFR versus invasive FFR was superior to cCTA alone on a per-vessel level (78% vs. 60%) and per patient level (83% vs. 73%) across all Agatston score categories. No statistically significant differences in the diagnostic accuracy, sensitivity, or specificity of CT-FFR were observed across the categories. CT-FFR showed good discriminatory power in vessels with high Agatston scores (CAC ≥400) and high performance in low-to-intermediate Agatston scores (CAC >0 to <400) with a statistically significant difference in the area under the receiver-operating characteristic curve (AUC) (AUC: 0.71 [95% confidence interval (CI): 0.57 to 0.85] vs. 0.85 [95% CI: 0.82 to 0.89], p = 0.04). CT-FFR showed superior diagnostic value over cCTA in vessels with high Agatston scores (CAC ≥ 400: AUC 0.71 vs. 0.55, p = 0.04) and low-to-intermediate Agatston scores (CAC >0 to <400: AUC 0.86 vs. 0.63, p < 0.001). CONCLUSIONS:Machine-learning-based CT-FFR showed superior diagnostic performance over cCTA alone in CAC with a significant difference in the performance of CT-FFR as calcium burden/Agatston calcium score increased. (Machine Learning Based CT Angiography Derived FFR: a Multicenter, Registry [MACHINE] NCT02805621).
Relationship of epicardial fat volume with coronary plaque characteristics, coronary artery calcification score, coronary stenosis, and CT-FFR for lesion-specific ischemia in patients with known or suspected coronary artery disease.
Xie Zhen,Zhu Jing,Li Wenjia,Liu Luzhou,Zhuo Kaimin,Yang Ru,Hu Fubi
International journal of cardiology
BACKGROUND:We explored the association of epicardial fat volume (EFV) with coronary plaque characteristics, coronary artery calcification (CAC) score, coronary stenosis, lesion-specific ischemia in patients with known or suspected coronary artery disease (CAD). METHODS:88 controls and 221 patients were analyzed in the study. High-risk plaque was defined as existing≥2 features, including positive remodeling, low attenuation, napkin-ring sign and spotty calcification. EFV, CAC score was measured. The severity of coronary stenosis was quantified using Gensini score. CT-FFR was performed in three major coronary arteries, with a threshold of ≤0.8 considered the presence of ischemia. Univariate and multivariate regression was used to evaluate the association of EFV with CAD, palque characteristics, CAC score, Gensini score, and lesion-specific ischemia derived from CT-FFR. RESULTS:Median EFV was 104.97 cm (85.47-136.09) in controls and 129.28cm (101.19-159.44) in patients (P < 0.001). Logistic regression analysis revealed a significant association of EFV with CAD even after adjusting for confounding factors (P < 0.05). At linear regression analysis, EFV was significantly correlated with high-risk plaque and lesion-specific ischemia, but not with non-calcified plaque, mixed plaque, calcified plaque, CAC score and Gensini score (P ≥ 0.05). CONCLUSION:We found that EFV was associated with CAD, suggesting that it may be a promising marker of CAD. EFV was also correlated with high-risk plaque and lesion-specific ischemia, indicatingindicat that EAT was likely to be involved in myocardial ischemia and had the potential to definite patients' risk profile.
CT FFR for Ischemia-Specific CAD With a New Computational Fluid Dynamics Algorithm: A Chinese Multicenter Study.
Tang Chun Xiang,Liu Chun Yu,Lu Meng Jie,Schoepf U Joseph,Tesche Christian,Bayer Richard R,Hudson H Todd,Zhang Xiao Lei,Li Jian Hua,Wang Yi Ning,Zhou Chang Sheng,Zhang Jia Yin,Yu Meng Meng,Hou Yang,Zheng Min Wen,Zhang Bo,Zhang Dai Min,Yi Yan,Ren Yuan,Li Chen Wei,Zhao Xi,Lu Guang Ming,Hu Xiu Hua,Xu Lei,Zhang Long Jiang
JACC. Cardiovascular imaging
OBJECTIVES:The aim of this study was to validate the feasibility of a novel structural and computational fluid dynamics-based fractional flow reserve (FFR) algorithm for coronary computed tomography angiography (CTA), using alternative boundary conditions to detect lesion-specific ischemia. BACKGROUND:A new model of computed tomographic (CT) FFR relying on boundary conditions derived from structural deformation of the coronary lumen and aorta with transluminal attenuation gradient and assumptions regarding microvascular resistance has been developed, but its accuracy has not yet been validated. METHODS:A total of 338 consecutive patients with 422 vessels from 9 Chinese medical centers undergoing CTA and invasive FFR were retrospectively analyzed. CT FFR values were obtained on a novel on-site computational fluid dynamics-based CT FFR (uCT-FFR [version 1.5, United-Imaging Healthcare, Shanghai, China]). Performance characteristics of uCT-FFR and CTA in detecting lesion-specific ischemia in all lesions, intermediate lesions (luminal stenosis 30% to 70%), and "gray zone" lesions (FFR 0.75 to 0.80) were calculated with invasive FFR as the reference standard. The effect of coronary calcification on uCT-FFR measurements was also assessed. RESULTS:Per vessel sensitivities, specificities, and accuracies of 0.89, 0.91, and 0.91 with uCT-FFR, 0.92, 0.34, and 0.55 with CTA, and 0.94, 0.37, and 0.58 with invasive coronary angiography, respectively, were found. There was higher specificity, accuracy, and AUC for uCT-FFR compared with CTA and qualitative invasive coronary angiography in all lesions, including intermediate lesions (p < 0.001 for all). No significant difference in diagnostic accuracy was observed in the "gray zone" range versus the other 2 lesion groups (FFR ≤0.75 and >0.80; p = 0.397) and in patients with "gray zone" versus FFR ≤0.75 (p = 0.633) and versus FFR >0.80 (p = 0.364), respectively. No significant difference in the diagnostic performance of uCT-FFR was found between patients with calcium scores ≥400 and <400 (p = 0.393). CONCLUSIONS:This novel computational fluid dynamics-based CT FFR approach demonstrates good performance in detecting lesion-specific ischemia. Additionally, it outperforms CTA and qualitative invasive coronary angiography, most notably in intermediate lesions, and may potentially have diagnostic power in gray zone and highly calcified lesions.
The effect of coronary calcification on diagnostic performance of machine learning-based CT-FFR: a Chinese multicenter study.
Di Jiang Meng,Zhang Xiao Lei,Liu Hui,Tang Chun Xiang,Li Jian Hua,Wang Yi Ning,Xu Peng Peng,Zhou Chang Sheng,Zhou Fan,Lu Meng Jie,Zhang Jia Yin,Yu Meng Meng,Hou Yang,Zheng Min Wen,Zhang Bo,Zhang Dai Min,Yi Yan,Xu Lei,Hu Xiu Hua,Yang Jian,Lu Guang Ming,Ni Qian Qian,Zhang Long Jiang
OBJECTIVE:To investigate the effect of coronary calcification morphology and severity on the diagnostic performance of machine learning (ML)-based coronary CT angiography (CCTA)-derived fractional flow reserve (CT-FFR) with FFR as a reference standard. METHODS:A total of 442 patients (61.2 ± 9.1 years, 70% men) with 544 vessels who underwent CCTA, ML-based CT-FFR, and invasive FFR from China multicenter CT-FFR study were enrolled. The effect of calcification arc, calcification remodeling index (CRI), and Agatston score (AS) on the diagnostic performance of CT-FFR was investigated. CT-FFR ≤ 0.80 and lumen reduction ≥ 50% determined by CCTA were identified as vessel-specific ischemia with invasive FFR as a reference standard. RESULTS:Compared with invasive FFR, ML-based CT-FFR yielded an overall sensitivity of 0.84, specificity of 0.94, and accuracy of 0.90 in a total of 344 calcification lesions. There was no statistical difference in diagnostic accuracy, sensitivity, or specificity of CT-FFR across different calcification arc, CRI, or AS levels. CT-FFR exhibited improved discrimination of ischemia compared with CCTA alone in lesions with mild-to-moderate calcification (AUC, 0.89 vs. 0.69, p < 0.001) and lesions with CRI ≥ 1 (AUC, 0.89 vs. 0.71, p < 0.001). The diagnostic accuracy and specificity of CT-FFR were higher than CCTA alone in patients and vessels with mid (100 to 299) or high (≥ 300) AS. CONCLUSION:Coronary calcification morphology and severity did not influence diagnostic performance of CT-FFR in ischemia detection, and CT-FFR showed marked improved discrimination of ischemia compared with CCTA alone in the setting of calcification. KEY POINTS:• CT-FFR provides superior diagnostic performance than CCTA alone regardless of coronary calcification. • No significant differences in the diagnostic performance of CT-FFR were observed in coronary arteries with different coronary calcification arcs and calcified remodeling indexes. • No significant differences in the diagnostic accuracy of CT-FFR were observed in coronary arteries with different coronary calcification score levels.
Influence of heart rate and coronary artery calcification on image quality and diagnostic performance of coronary CT angiography: comparison between 96-row detector dual source CT and 256-row multidetector CT.
Qian Wen,Liu Wangyan,Zhu Yinsu,Wang Jun,Chen Yang,Meng Haoyu,Chen Leilei,Xu Yi,Zhu Xiaomei
Journal of X-ray science and technology
BACKGROUND:CT-derived fractional flow reserve (FFRCT) and diagnostic accuracy rely on good image quality during coronary CT angiography (CCTA). OBJECTIVE:To investigate whether heart rate (HR) and coronary artery calcium (CAC) score decrease image quality and diagnostic performance of two advanced CT scanners including 96-row detector dual source CT (DSCT) and 256-row multidetector CT (MDCT). METHODS:First, 79 patients who underwent CCTA (42 with DSCT and 37 with MDCT) and invasive coronary angiography (ICA) are enrolled. Next, coronary segments with excellent image quality are evaluated and the percentage is calculated. Then, diagnostic accuracy in detecting significant diameter stenosis is presented with ICA as the reference standard. RESULTS:Compared with the DSCT, the percentage of coronary segments with excellent image quality is lower (P = 0.010) while diagnostic accuracy on per-segment level is improved (P = 0.037) using MDCT. CAC score≥400 is the only independent factor influencing the percentage of coronary segments with excellent image quality [odds ratio (OR): DSCT, 3.096 and MDCT, 1.982] and segmental diagnostic accuracy (OR: DSCT, 2.630 and MDCT, 2.336) for both scanners. HR≥70 bpm (OR: 5.506) is the independent factor influencing the percentage of coronary segments with excellent image quality with MDCT. CONCLULSION:During CCTA, CAC score≥400 still decreases the proportion of coronary segments with excellent image quality and diagnostic accuracy with advanced CT scanners. HR≥70 bpm is another factor causing image quality decreasing with MDCT.
Relevance of anatomical, plaque, and hemodynamic characteristics of non-obstructive coronary lesions in the prediction of risk for acute coronary syndrome.
Park Jiesuck,Lee Joo Myung,Koo Bon-Kwon,Choi Gilwoo,Hwang Doyeon,Rhee Tae-Min,Yang Seokhun,Park Jonghanne,Zhang Jinlong,Kim Kyung-Jin,Tong Yaliang,Doh Joon-Hyung,Nam Chang-Wook,Shin Eun-Seok,Cho Young-Seok,Chun Eun Ju,Choi Jin-Ho,Norgaard Bjarne L,Christiansen Evald H,Niemen Koen,Otake Hiromasa,Penicka Martin,de Bruyne Bernard,Kubo Takashi,Akasaka Takashi,Narula Jagat,Douglas Pamela S,Taylor Charles A
OBJECTIVES:We explored the anatomical, plaque, and hemodynamic characteristics of high-risk non-obstructive coronary lesions that caused acute coronary syndrome (ACS). METHODS:From the EMERALD study which included ACS patients with available coronary CT angiography (CCTA) before the ACS, non-obstructive lesions (percent diameter stenosis < 50%) were selected. CCTA images were analyzed for lesion characteristics by independent CCTA and computational fluid dynamics core laboratories. The relative importance of each characteristic was assessed by information gain. RESULTS:Of the 132 lesions, 24 were the culprit for ACS. The culprit lesions showed a larger change in FFR across the lesion (ΔFFR) than non-culprit lesions (0.08 ± 0.07 vs 0.05 ± 0.05, p = 0.012). ΔFFR showed the highest information gain (0.051, 95% confidence interval [CI] 0.050-0.052), followed by low-attenuation plaque (0.028, 95% CI 0.027-0.029) and plaque volume (0.023, 95% CI 0.022-0.024). Lesions with higher ΔFFR or low-attenuation plaque showed an increased risk of ACS (hazard ratio [HR] 3.25, 95% CI 1.31-8.04, p = 0.010 for ΔFFR; HR 2.60, 95% CI 1.36-4.95, p = 0.004 for low-attenuation plaque). The prediction model including ΔFFR, low-attenuation plaque and plaque volume showed the highest ability in ACS prediction (AUC 0.725, 95% CI 0.724-0.727). CONCLUSION:Non-obstructive lesions with higher ΔFFR or low-attenuation plaque showed a higher risk of ACS. The integration of anatomical, plaque, and hemodynamic characteristics can improve the noninvasive prediction of ACS risk in non-obstructive lesions. KEY POINTS:• Change in FFR across the lesion (ΔFFR ) was the most important predictor of ACS risk in non-obstructive lesions. • Non-obstructive lesions with higher ΔFFR or low-attenuation plaque were associated with a higher risk of ACS. • The integration of anatomical, plaque, and hemodynamic characteristics can improve the noninvasive prediction of ACS risk.
Coronary calcium scoring and computed tomography angiography: current indications, future applications.
Alani Anas,Budoff Matthew J
Coronary artery disease
Cardiac computed tomography (CT) has evolved at a rapid pace over the last few years. The improved spatial and temporal resolution allows collection of valuable information about the coronary arteries and atherosclerosis not obtainable by other noninvasive modalities. Coronary artery calcium acquisition is more straightforward, and large datasets are available to help validate its use in risk stratification and prediction of future events. The data from CT angiography has excellent negative predictive value to rule out stenosis, with potential use in plaque characterization to predict plaque vulnerability and perfusion. In addition, a recent novel technique with fractional flow reserve CT (FFRCT) has been shown to predict ischemia-causing lesions noninvasively. The ability of FFRCT to reduce the need for invasive angiography has recently been studied for the third time in a multicenter study, which showed high concordance with the results of invasive fractional flow reserve.
Additive diagnostic value of atherosclerotic plaque characteristics to non-invasive FFR for identification of lesions causing ischaemia: results from a prospective international multicentre trial.
Nakazato Ryo,Park Hyung-Bok,Gransar Heidi,Leipsic Jonathon A,Budoff Matthew J,Mancini G B John,Erglis Andrejs,Berman Daniel S,Min James K
EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
AIMS:We evaluated the association between atherosclerotic plaque characteristics (APCs) by CT -including positive remodelling (PR), low attenuation plaque (LAP) and spotty calcification (SC)- and lesion ischaemia by fractional flow reserve (FFR). METHODS AND RESULTS:Two hundred and fifty-two patients (17 centres, five countries) underwent CT, FFR derived from CT (FFRCT) with invasive FFR performed for 407 coronary lesions. FFR ≤0.8 was indicative of lesion-specific ischaemia. CT diameter ≥50% stenosis was considered obstructive. APCs by CT were defined as: (1) PR, lesion diameter/reference diameter >1.10; (2) LAP, any voxel <30 HU; and (3) SC, nodular calcified plaque <3 mm. Odds ratios (OR) and area under the ROC curve (AUC) of APCs for lesion-specific ischaemia were analysed. PR, LAP and SC were associated with ischaemia, with a three to fivefold higher prevalence than in non-ischaemic lesions. Among individual APC, PR (OR 4.7, p<0.001), but not SC or LAP, was strongly associated with lesion-specific ischaemia and provided incremental prediction for lesion-specific ischaemia over CT stenosis plus FFRCT (AUC 0.87 vs. 0.83, p=0.002). CONCLUSIONS:APCs' features -especially PR- by CT improve identification and reclassification of coronary lesions which cause ischaemia over CT stenosis and FFRCT.
Identification of High-Risk Plaques Destined to Cause Acute Coronary Syndrome Using Coronary Computed Tomographic Angiography and Computational Fluid Dynamics.
Lee Joo Myung,Choi Gilwoo,Koo Bon-Kwon,Hwang Doyeon,Park Jonghanne,Zhang Jinlong,Kim Kyung-Jin,Tong Yaliang,Kim Hyun Jin,Grady Leo,Doh Joon-Hyung,Nam Chang-Wook,Shin Eun-Seok,Cho Young-Seok,Choi Su-Yeon,Chun Eun Ju,Choi Jin-Ho,Nørgaard Bjarne L,Christiansen Evald H,Niemen Koen,Otake Hiromasa,Penicka Martin,de Bruyne Bernard,Kubo Takashi,Akasaka Takashi,Narula Jagat,Douglas Pamela S,Taylor Charles A,Kim Hyo-Soo
JACC. Cardiovascular imaging
OBJECTIVES:The authors investigated the utility of noninvasive hemodynamic assessment in the identification of high-risk plaques that caused subsequent acute coronary syndrome (ACS). BACKGROUND:ACS is a critical event that impacts the prognosis of patients with coronary artery disease. However, the role of hemodynamic factors in the development of ACS is not well-known. METHODS:Seventy-two patients with clearly documented ACS and available coronary computed tomographic angiography (CTA) acquired between 1 month and 2 years before the development of ACS were included. In 66 culprit and 150 nonculprit lesions as a case-control design, the presence of adverse plaque characteristics (APC) was assessed and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFR], change in FFR across the lesion [△FFR], wall shear stress [WSS], and axial plaque stress) were analyzed using computational fluid dynamics. The best cut-off values for FFR, △FFR, WSS, and axial plaque stress were used to define the presence of adverse hemodynamic characteristics (AHC). The incremental discriminant and reclassification abilities for ACS prediction were compared among 3 models (model 1: percent diameter stenosis [%DS] and lesion length, model 2: model 1 + APC, and model 3: model 2 + AHC). RESULTS:The culprit lesions showed higher %DS (55.5 ± 15.4% vs. 43.1 ± 15.0%; p < 0.001) and higher prevalence of APC (80.3% vs. 42.0%; p < 0.001) than nonculprit lesions. Regarding hemodynamic parameters, culprit lesions showed lower FFR and higher △FFR, WSS, and axial plaque stress than nonculprit lesions (all p values <0.01). Among the 3 models, model 3, which included hemodynamic parameters, showed the highest c-index, and better discrimination (concordance statistic [c-index] 0.789 vs. 0.747; p = 0.014) and reclassification abilities (category-free net reclassification index 0.287; p = 0.047; relative integrated discrimination improvement 0.368; p < 0.001) than model 2. Lesions with both APC and AHC showed significantly higher risk of the culprit for subsequent ACS than those with no APC/AHC (hazard ratio: 11.75; 95% confidence interval: 2.85 to 48.51; p = 0.001) and with either APC or AHC (hazard ratio: 3.22; 95% confidence interval: 1.86 to 5.55; p < 0.001). CONCLUSIONS:Noninvasive hemodynamic assessment enhanced the identification of high-risk plaques that subsequently caused ACS. The integration of noninvasive hemodynamic assessments may improve the identification of culprit lesions for future ACS. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary CT Angiography and Computational Fluid Dynamic [EMERALD]; NCT02374775).
Diagnostic performance of perivascular fat attenuation index to predict hemodynamic significance of coronary stenosis: a preliminary coronary computed tomography angiography study.
Yu Mengmeng,Dai Xu,Deng Jianhong,Lu Zhigang,Shen Chengxing,Zhang Jiayin
OBJECTIVE:This study aimed to investigate the association between perivascular fat attenuation index (FAI) and hemodynamic significance of coronary lesions. METHODS:Patients with stable angina who underwent coronary computed tomography (CT) angiography and invasive fractional flow reserve (FFR) measurement within 2 weeks were retrospectively included. Lesion-based perivascular FAI, high-risk plaque features, total plaque volume (TPV), machine learning-based FFR, and other parameters were recorded. Lesions with invasive FFR ≤ 0.8 were considered functionally significant. RESULTS:This study included 167 patients with 219 lesions. Diameter stenosis (DS), lesion length, TPV, and perivascular FAI were significantly larger or longer in the group of hemodynamically significant lesions (FFR ≤ 0.8). In addition, smaller FFR value was associated with functionally significant lesions (0.720 ± 0.11 vs 0.846 ± 0.10, p < 0.001). No significant difference was found between the hemodynamically significant and insignificant subgroups with respect to CT-derived high-risk plaque features. According to multivariate analysis, DS, TPV, and perivascular FAI were significant predictors of lesion-specific ischemia. When integrating DS, TPV, and perivascular FAI, the area under the curve (AUC) of this combined method was 0.821, which was similar to that of FFR (AUC, 0.821 vs 0.850; p = 0.426). The diagnostic accuracy of FFR was higher than that of the combined approach, but the difference was statistically insignificant (79.0% vs 74.0%, p = 0.093). CONCLUSIONS:Perivascular FAI was significantly higher for flow-limiting lesions than for non-flow-limiting lesions. The combined use of FAI, TPV, and DS could predict ischemic coronary stenosis with high diagnostic accuracy. KEY POINTS:• Perivascular FAI was significantly higher for flow-limiting lesions than for non-flow-limiting lesions. • Combined use of FAI, plaque volume, and DS provided diagnostic performance comparable to that of machine learning-based FFR for predicting ischemic coronary stenosis. • No significant difference was found between the hemodynamically significant and insignificant subgroups with respect to CT-derived high-risk plaque features.
Functional and Anatomical Testing in Intermediate Risk Chest Pain Patients with a High Coronary Calcium Score: Rationale and Design of the FACC Study.
Øvrehus Kristian A,Veien Karsten T,Lambrechtsen Jess,Rohold Allan,Steffensen Flemming H,Gerke Oke,Jensen Lisette O,Mickley Hans
Current guidelines do not recommend coronary computed tomography angiography (CCTA) in patients with high levels of coronary calcium, as severe calcification leads to difficulties in estimating stenosis severity due to blooming artifacts obscuring the vessel lumen. Whether the CCTA-derived fractional flow reserve (FFRCT) improves the diagnostic performance of CCTA in patients with high levels of coronary calcification has not been sufficiently evaluated. We hypothesize that a noninvasive diagnostic strategy using FFRCT will perform comparably to an invasive diagnostic strategy in the detection of hemodynamically significant coronary artery disease (CAD) in clinical stable chest pain patients with high levels of coronary calcium. In this prospective, blinded, multicenter study, patients with suspected stable CAD referred for CCTA and demonstrating an Agatston score >399 will be included. Patients accepting inclusion will, in addition to CCTA, undergo invasive coronary angiography (ICA) and invasive FFR measurement. FFRCT analyses are performed by an external core laboratory blinded to any patient data, and the FFRCT results are blinded to all participating study sites. The primary objective is to evaluate whether FFRCT can identify patients with and without hemodynamically significant CAD, when ICA with FFR is the reference standard. A negative study result would question the clinical usefulness of FFRCT in patients with high levels of coronary calcium. A positive study result, however, would imply a reduction in the number of patients referred for coronary catheterization and, at the same time, increase the proportion of patients with hemodynamically significant CAD at the subsequent invasive examination.
Non obstructive high-risk plaque but not calcified by coronary CTA, and the G-score predict ischemia.
Feuchtner Gudrun M,Barbieri Fabian,Langer Christian,Beyer Christoph,Widmann Gerlig,Friedrich Guy J,Cartes-Zumelzu Fabiola,Plank Fabian
Journal of cardiovascular computed tomography
BACKGROUND:The association of plaque morphology with ischemia in non-obstructive lesions has not been fully eludicated: Calcium density and high-risk plaque features have not been explored. OBJECTIVES:to assess whether high-risk plaque or calcified, and global mixed including non-calcified plaque burden (G-score) by coronary CTA predict ischemia in non-obstructive lesions using non-invasive fractional flow reserve (FFR). METHODS:In 106 patients with low-to-intermediate pre-test probability referred to coronary 128-slice dual source CTA, lesion-based and distal FFR were computated. The 4 high-risk-plaque criteria: Low-attenuation-plaque, Napkin Ring Sign, positive remodelling and spotty calcification were recorded. Plaque density (HU) and stenosis (MLA,MLD,%area,%diameter stenosis) were quantified. Plaque composition was classified as type 1-4:1 = calcified, 2 = mixed (calcified > non-calcified), 3 = mixed (non-calcified > calcified), 4 = non-calcified, and expressed by the G-score: Z = Sum of type 1-4 per segment. The total plaque segment involvement score (SIS) and the Coronary Calcium Score (Agatston) were calculated. RESULTS:89 non-obstructive lesions were included. Both lesion-based and distal FFR were lower in high-risk-plaque as compared to calcified (0.85 vs 0.93, p < 0.001 and 0.79 vs 0.86, p = 0.002). The prevalence of lesion-based ischemia (FFR<0.8) was higher in high-risk-plaque as compared to calcified (25% vs. 2.5%, p = 0.007). Similarly, the rate of distal ischemia (40% vs 17.5%) was higher, respectively. Lower plaque density (HU) indicating higher lipid plaque component (p = 0.024) predicted lesion based FFR in low attenuation plaque. For all lesions (n = 89) including calcified (p = 0.003), the correlation enhanced. Positive remodelling and an increasing non-calcified plaque burden (G-score) in relation to calcified were associated with lower FFR distal (p = 0.042), but not the SIS and calcium score. CONCLUSION:High-risk-plaque but not calcified, an increasing lipid-necrotic-core component and non-calcified mixed plaque burden (G-score) predict ischemia in non-obstructive lesions (INOCA), while an increasing calcium compactness acts contrary.
Changes in coronary atherosclerosis, composition, and fractional flow reserve evaluated by coronary computed tomography angiography in patients with type 2 diabetes.
Nozue Tsuyoshi,Takamura Takeshi,Fukui Kazuki,Sozu Takashi,Tanaka Yuji,Hibi Kiyoshi,Kishi Satoru,Michishita Ichiro
International journal of cardiology. Heart & vasculature
Background:The use of coronary computed tomography angiography (CCTA) for noninvasive anatomic detection of coronary artery disease is increasing. Recently, fractional flow reserve (FFR) assessment using routinely acquired CCTA datasets (FFR) has been developed. However, there are no reports about changes in coronary atherosclerosis, composition, and FFR in patients with type 2 diabetes. Methods:This prospective, multicenter, observational trial evaluated changes in coronary atherosclerosis after alogliptin therapy in patients with type 2 diabetes. Fifty-one patients with type 2 diabetes who underwent CCTA examination and having intermediate coronary artery stenosis were treated with 25 mg of alogliptin. After 48 weeks, CCTA examination was repeated. The primary endpoint was changes in FFR, and the secondary endpoint was changes in total atheroma volume (TAV) from the baseline to the 48-week follow-up. Results:The FFR decreased from the baseline to follow-up, but not significantly. A significant increase in TAV (from 658.5 mm to 668.9 mm, = 0.048) was observed. Vessel volume tended to increase, whereas percentage atheroma volume and lumen volume did not change. A significant negative correlation was observed between percentage change in TAV and change in FFR ( = -0.185, = 0.048). A significant increase in calcified plaques ( = 0.01) and a decrease in intermediate-attenuation plaques ( = 0.006) was observed. Conclusions:In Japanese patients with diabetes and intermediate coronary artery stenosis, alogliptin could not improve FFR or reduce atheroma volume, whereas the plaque composition changed. A progression of atheroma volume was associated with a reduction in FFR.
Coronary plaque quantification and fractional flow reserve by coronary computed tomography angiography identify ischaemia-causing lesions.
Gaur Sara,Øvrehus Kristian Altern,Dey Damini,Leipsic Jonathon,Bøtker Hans Erik,Jensen Jesper Møller,Narula Jagat,Ahmadi Amir,Achenbach Stephan,Ko Brian S,Christiansen Evald Høj,Kaltoft Anne Kjer,Berman Daniel S,Bezerra Hiram,Lassen Jens Flensted,Nørgaard Bjarne Linde
European heart journal
AIMS:Coronary plaque characteristics are associated with ischaemia. Differences in plaque volumes and composition may explain the discordance between coronary stenosis severity and ischaemia. We evaluated the association between coronary stenosis severity, plaque characteristics, coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFRCT), and lesion-specific ischaemia identified by FFR in a substudy of the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). METHODS AND RESULTS:Coronary CTA stenosis, plaque volumes, FFRCT, and FFR were assessed in 484 vessels from 254 patients. Stenosis >50% was considered obstructive. Plaque volumes (non-calcified plaque [NCP], low-density NCP [LD-NCP], and calcified plaque [CP]) were quantified using semi-automated software. Optimal thresholds of quantitative plaque variables were defined by area under the receiver-operating characteristics curve (AUC) analysis. Ischaemia was defined by FFR or FFRCT ≤0.80. Plaque volumes were inversely related to FFR irrespective of stenosis severity. Relative risk (95% confidence interval) for prediction of ischaemia for stenosis >50%, NCP ≥185 mm(3), LD-NCP ≥30 mm(3), CP ≥9 mm(3), and FFRCT ≤0.80 were 5.0 (3.0-8.3), 3.7 (2.4-5.6), 4.6 (2.9-7.4), 1.4 (1.0-2.0), and 13.6 (8.4-21.9), respectively. Low-density NCP predicted ischaemia independent of other plaque characteristics. Low-density NCP and FFRCT yielded diagnostic improvement over stenosis assessment with AUCs increasing from 0.71 by stenosis >50% to 0.79 and 0.90 when adding LD-NCP ≥30 mm(3) and LD-NCP ≥30 mm(3) + FFRCT ≤0.80, respectively. CONCLUSION:Stenosis severity, plaque characteristics, and FFRCT predict lesion-specific ischaemia. Plaque assessment and FFRCT provide improved discrimination of ischaemia compared with stenosis assessment alone.
Assessment of factors associated with measurability of fractional flow reserve derived from coronary computed tomography angiography in type 2 diabetic patients with intermediate coronary artery stenosis.
Nozue Tsuyoshi,Takamura Takeshi,Fukui Kazuki,Hibi Kiyoshi,Kishi Satoru,Michishita Ichiro
The international journal of cardiovascular imaging
Recently, fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) (FFR) has been developed. However, FFR cannot be calculated for all patients from CCTA datasets. The purpose of the present study, therefore, was to evaluate the predictors that results in cases being inappropriate for FFR processing. This study was a sub-analysis of the TRACT trial, from which 50 patients were divided into 2 groups according to FFR measurability (measurable [group M] or not measurable [group N]) using CCTA examination at baseline. Thirty-nine (78%) patients comprised group M and 11 (22%) comprised group N. Heart rate at CCTA examination (72 beats/min vs. 63 beats/min; p = 0.007) and Agatston score (665 vs. 33; p = 0.002) in group N were significantly higher than those in group M. Multivariate logistic regression analyses revealed that heart rate at CCTA examination (OR 1.348 [95% CI 1.167-1.556]; p < 0.001) and Agatston score (OR 1.002 [95% CI 1.000-1.003]; p = 0.004) were significant, independent factors associated with non-measurability of FFR. The frequency of poor image quality was highest in patients with heart rate > 65 beats/min and Agatston score > 400 (p < 0.0001). In conclusions, high heart rate at the time of CCTA examination and higher Agatston score were associated with poor image quality that resulted in cases being inappropriate for FFR processing. Heart rate control at CCTA examination is necessary to acquire good-quality images required for computing FFR.
Influence of Coronary Calcification on the Diagnostic Performance of CT Angiography Derived FFR in Coronary Artery Disease: A Substudy of the NXT Trial.
Nørgaard Bjarne L,Gaur Sara,Leipsic Jonathon,Ito Hiroshi,Miyoshi Toru,Park Seung-Jung,Zvaigzne Ligita,Tzemos Nikolaos,Jensen Jesper M,Hansson Nicolaj,Ko Brian,Bezerra Hiram,Christiansen Evald H,Kaltoft Anne,Lassen Jens F,Bøtker Hans Erik,Achenbach Stephan
JACC. Cardiovascular imaging
OBJECTIVES:The goal of this study was to examine the diagnostic performance of noninvasive fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFRCT) in relation to coronary calcification severity. BACKGROUND:FFRCT has shown promising results in identifying lesion-specific ischemia. The extent to which the severity of coronary calcification affects the diagnostic performance of FFRCT is not known. METHODS:Coronary calcification was assessed by using the Agatston score (AS) in 214 patients suspected of having coronary artery disease who underwent coronary CTA, FFRCT, and FFR (FFR examination was performed in 333 vessels). The diagnostic performance of FFRCT (≤0.80) in identifying vessel-specific ischemia (FFR ≤0.80) was investigated across AS quartiles (Q1 to Q4) and for discrimination of ischemia in patients and vessels with a low-mid AS (Q1 to Q3) versus a high AS (Q4). Coronary CTA stenosis was defined as lumen reduction >50%. RESULTS:Mean ± SD per-patient and per-vessel AS were 302 ± 468 (range 0 to 3,599) and 95 ± 172 (range 0 to 1,703), respectively. There was no statistical difference in diagnostic accuracy, sensitivity, or specificity of FFRCT across AS quartiles. Discrimination of ischemia by FFRCT was high in patients with a high AS (416 to 3,599) and a low-mid AS (0 to 415), with no difference in area under the receiver-operating characteristic curve (AUC) (0.86 [95% confidence interval (CI): 0.76 to 0.96] vs. 0.92 [95% CI: 0.88 to 0.96]) (p = 0.45). Similarly, discrimination of ischemia by FFRCT was high in vessels with a high AS (121 to 1,703) and a low-mid AS (0 to 120) (AUC: 0.91 [95% CI: 0.85 to 0.97] vs. 0.95 [95% CI: 0.91 to 0.98]; p = 0.65). Diagnostic accuracy and specificity of FFRCT were significantly higher than for stenosis assessment in each AS quartile at the per-patient (p < 0.001) and per-vessel (p < 0.05) level with similar sensitivity. In vessels with a high AS, FFRCT exhibited improved discrimination of ischemia compared with coronary CTA alone (AUC: 0.91 vs. 0.71; p = 0.004), whereas on a per-patient level, the difference did not reach statistical significance (AUC: 0.86 vs. 0.72; p = 0.09). CONCLUSIONS:FFRCT provided high and superior diagnostic performance compared with coronary CTA interpretation alone in patients and vessels with a high AS.
Diagnostic value of comprehensive on-site and off-site coronary CT angiography for identifying hemodynamically obstructive coronary artery disease.
Bom Michiel J,Driessen Roel S,Kurata Akira,van Diemen Pepijn A,Everaars Henk,Schumacher Stefan P,de Winter Ruben W,van de Ven Peter M,van Rossum Albert C,Taylor Charles A,Min James K,Leipsic Jonathon A,Danad Ibrahim,Knaapen Paul
Journal of cardiovascular computed tomography
BACKGROUND:This study aimed to investigate the diagnostic value of comprehensive on-site coronary computed tomography angiography (CCTA) using stenosis and plaque measures and subtended myocardial mass (V) for fractional flow reserve (FFR) defined hemodynamically obstructive coronary artery disease (CAD). Additionally, the incremental diagnostic value of off-site CT-derived FFR (FFR) was assessed. METHODS:Prospectively enrolled patients underwent CCTA followed by invasive FFR interrogation of all major coronary arteries. Vessels with ≥30% stenosis were included for analysis. On-site CCTA assessment included qualitative and quantitative stenosis (visual grading and minimal lumen area, MLA) and plaque measures (characteristics and volumes), and V. Diagnostic value of comprehensive on-site CCTA assessment was tested by comparing area under the curves (AUC). In vessels with available FFR, the incremental value of off-site FFR was tested. RESULTS:In 236 vessels (132 patients), MLA, positive remodeling, non-calcified plaque volume, and V were independent on-site CCTA predictors for hemodynamically obstructive CAD (p < 0.05 for all). V/MLA outperformed all these on-site CCTA parameters (AUC = 0.85) and V was incremental to all other CCTA predictors (p = 0.02). In subgroup analysis (n = 194 vessels), diagnostic performance of FFR and V/MLA was similar (AUC 0.89 and 0.85 respectively, p = 0.25). Furthermore, diagnostic performance significantly albeit minimally increased when FFR was added to on-site CCTA assessment (ΔAUC = 0.03, p = 0.02). CONCLUSIONS:In comprehensive on-site CCTA assessment, V/MLA2 demonstrated greatest diagnostic value for hemodynamically obstructive CAD and V was incremental to all evaluated CCTA indices. Additionally, adding FFR only minimally increased diagnostic performance, demonstrating that on-site CCTA assessment is a reasonable alternative to FFR.
Serial coronary CT angiography-derived fractional flow reserve and plaque progression can predict long-term outcomes of coronary artery disease.
Yang Liu,Xu Peng Peng,Schoepf U Joseph,Tesche Christian,Pillai Balakrishnan,Savage Rock H,Tang Chun Xiang,Zhou Fan,Wei Hao Dong,Luo Zhong Qiang,Wang Qing Gen,Zhou Chang Sheng,Lu Meng Jie,Lu Guang Ming,Zhang Long Jiang
OBJECTIVE:To investigate the utility of coronary CT angiography-derived fractional flow reserve (FFR) and plaque progression in patients undergoing serial coronary CT angiography for predicting major adverse cardiovascular events (MACE). METHODS:This retrospective study evaluated patients suspected or known coronary artery disease who underwent serial coronary CT angiography examinations between January 2006 and December 2017 and followed up until June 2019. The primary endpoint was MACE, defined as acute coronary syndrome, rehospitalization due to progressive angina, percutaneous coronary intervention, or cardiac death. FFR and plaque parameters were analyzed on a per-vessel and per-patient basis. Univariable and multivariable COX regression analysis determined predictors of MACE. The prognostic value of FFR and plaque progression were assessed in nested models. RESULTS:Two hundred eighty-four patients (median age, 61 years (interquartile range, 54-70); 202 males) were evaluated. MACE was observed in 45 patients (15.8%, 45/284). By Cox multivariable regression modeling, vessel-specific FFR ≤ 0.80 was associated with a 2.4-fold increased risk of MACE (HR (95% CI): 2.4 (1.3-4.4); p = 0.005) and plaque progression was associated with a 9-fold increased risk of MACE (HR (95% CI): 9 (3.5-23); p < 0.001) after adjusting for clinical and imaging risk factors. FFR and plaque progression improved the prediction of events over coronary artery calcium (CAC) score and high-risk plaques (HRP) in the receiver operating characteristics analysis (area under the curve: 0.70 to 0.86; p = 0.002). CONCLUSIONS:Fractional flow reserve and plaque progression assessed by serial coronary CT angiography predicted the risk of future MACE. KEY POINTS:• Vessel-specific CT angiography-derived fractional flow reserve (FFR) ≤ 0.80 and plaque progression improved the prediction of events over current risk factors. • Major adverse cardiovascular events (MACE) significantly increased with the presence of plaque progression at follow-up stratified by the FFR change group.
Feasibility and diagnostic performance of fractional flow reserve measurement derived from coronary computed tomography angiography in real clinical practice.
Kawaji Tetsuma,Shiomi Hiroki,Morishita Hiroshi,Morimoto Takeshi,Taylor Charles A,Kanao Shotaro,Koizumi Koji,Kozawa Satoshi,Morihiro Kazuhisa,Watanabe Hirotoshi,Tazaki Junichi,Imai Masao,Saito Naritatsu,Shizuta Satoshi,Ono Koh,Togashi Kaori,Kimura Takeshi
The international journal of cardiovascular imaging
Non-invasive fractional flow reserve measured by coronary computed tomography angiography (FFR) has demonstrated a high diagnostic accuracy for detecting coronary artery disease (CAD) in selected patients in prior clinical trials. However, feasibility of FFR in unselected population have not been fully evaluated. Among 60 consecutive patients who had suspected significant CAD by coronary computed tomography angiography (CCTA) and were planned to undergo invasive coronary angiography, 48 patients were enrolled in this study comparing FFR with invasive fractional flow reserve (FFR) without any exclusion criteria for the quality of CCTA image. FFR was measured in a blinded fashion by an independent core laboratory. FFR value was evaluable in 43 out of 48 (89.6 %) patients with high prevalence of severe calcification in CCTA images [calcium score (CS) >400: 40 %, and CS > 1000: 19 %). Per-vessel FFR value showed good correlation with invasive FFR value (Spearman's rank correlation = 0.69, P < 0.001). The area under the receiver operator characteristics curve (AUC) of FFR was 0.87. Per-vessel accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 68.6, 92.9, 52.4, 56.5, and 91.7 %, respectively. Even in eight patients (13 vessels) with extremely severely calcified lesions (CS > 1000), per-vessel FFR value showed a diagnostic performance similar to that in patients with CS ≤ 1000 (Spearman's rank correlation = 0.81, P < 0.001). FFR could be measured in the majority of consecutive patients who had suspected significant CAD by CCTA in real clinical practice and demonstrated good diagnostic performance for detecting hemodynamically significant CAD even in patients with extremely severe calcified vessels.
Non-invasive fractional flow reserve in vessels without severe obstructive stenosis is associated with coronary plaque burden.
Doris Mhairi K,Otaki Yuka,Arnson Yoav,Tamarappoo Balaji,Goeller Markus,Gransar Heidi,Wang Frances,Hayes Sean,Friedman John,Thomson Louise,Slomka Piotr,Dey Damini,Berman Daniel
Journal of cardiovascular computed tomography
AIMS:Non-invasive fractional flow reserve derived from coronary CT angiography (FFR) has been shown to be predictive of lesion-specific ischemia as assessed by invasive fractional flow reserve (FFR). However, in practice, clinicians are often faced with an abnormal distal FFR in the absence of a discrete obstructive lesion. Using quantitative plaque analysis, we sought to determine the relationship between an abnormal whole vessel FFR (V-FFR) and quantitative measures of whole vessel atherosclerosis in coronary arteries without obstructive stenosis. METHODS:FFR was calculated in 155 consecutive patients undergoing coronary CTA with ≥25% but less than 70% stenosis in at least one major epicardial vessel. Semi-automated software was used to quantify plaque volumes (total plaque [TP], calcified plaque [CP], non-calcified plaque [NCP], low-density non-calcified plaque [LD-NCP]), remodeling index [RI], maximal contrast density difference [CDD] and percent diameter stenosis [%DS]. Abnormal V-FFR was defined as a minimum value of ≤0.75 across the vessel (at the most distal region where FFR was computed). RESULTS:Vessels with abnormal V-FFR had higher per-vessel TP (554 vs 331 mm), CP (59 vs 25 mm), NCP (429 vs 295 mm), LD-NCP (65 vs 35 mm) volume and maximum CDD (21 vs 14%) than those with normal V-FFR (median, p < 0.05 for all). Using a multivariate analysis to adjust for CDD and %DS, all measures of plaque volume were predictive of abnormal V-FFR (OR 2.09, 1.36, 1.95, 1.95 for TP, CP, NCP and LD-NCP volume, respectively; p < 0.05 for all). CONCLUSION:Abnormal V-FFR in vessels without obstructive stenosis is associated with multiple markers of diffuse non-obstructive atherosclerosis, independent of stenosis severity. Whole vessel FFR may represent a novel measure of diffuse coronary plaque burden.
Plaque Volume and Morphology are Associated with Fractional Flow Reserve Derived from Coronary Computed Tomography Angiography.
Nozue Tsuyoshi,Takamura Takeshi,Fukui Kazuki,Hibi Kiyoshi,Kishi Satoru,Michishita Ichiro
Journal of atherosclerosis and thrombosis
AIM:Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFR) accurately diagnoses ischemic lesions of intermediate stenosis severity. However, significant determinants of FFR have not been fully evaluated. METHODS:This was a sub-analysis of the Treatment of Alogliptin on Coronary Atherosclerosis Evaluated by Computed Tomography-Based Fractional Flow Reserve trial. Thirty-nine diabetic patients (117 vessels) with intermediate coronary artery stenosis [percent diameter stenosis (%DS) ＜70%] in whom FFR was measured were included in this study. CCTA-defined, vessel-based volumetric and morphological characteristics of plaques were examined to determine their ability to predict FFR. RESULTS:Patient-based, multivariate linear regression analysis showed that hemoglobinA1c, triglycerides, and the estimated glomerular filtration rate were significant independent factors associated with FFR. Vessel-based, univariate linear regression analysis showed that the total atheroma volume (r=－0.233, p=0.01) and the percentage atheroma volume (PAV) (r=－0.284, p=0.002) as well as %DS (r=－0.316, p=0.006) were significant determinants of FFR. Among the plaque components, significant negative correlations were observed between FFR and low- (r=－0.248, p=0.007) or intermediate-attenuation plaque volume (r=－0.186, p=0.045), whereas calcified plaque volume was not associated with FFR. In the left anterior descending coronary artery (LAD), the plaque volume of each component was associated with FFR. CONCLUSIONS:Plaque volume, PAV, and %DS were significant determinants of FFR. Plaque morphology, particularly in LAD, was associated with FFR in diabetic patients with intermediate coronary artery stenosis.
Clinical outcomes following real-world computed tomography angiography-derived fractional flow reserve testing in chronic coronary syndrome patients with calcification.
Nørgaard Bjarne L,Mortensen Martin B,Parner Erik,Leipsic Jonathon,Steffensen Flemming H,Grove Erik Lerkevang,Mathiassen Ole N,Sand Niels Peter,Pedersen Kamilla,Riedl Katharina A,Engholm Morten,Bøtker Hans Erik,Jensen Jesper M
European heart journal cardiovascular Imaging
AIMS :This study sought to investigate outcomes following a normal CT-derived fractional flow reserve (FFRCT) result in patients with moderate stenosis and coronary artery calcification, and to describe the relationship between the extent of calcification, stenosis, and FFRCT. METHODS AND RESULTS:Data from 975 consecutive patients suspected of chronic coronary syndrome with stenosis (30-70%) determined by computed CT angiography and FFRCT to guide downstream management decisions were reviewed. Median (range) follow-up time was 2.2 (0.5-4.2) years. Coronary artery calcium (CAC) scores were ≥400 in 25%, stenosis ≥50% in 83%, and FFRCT >0.80 in 51% of the patients. There was a lower incidence of the composite endpoint (death, myocardial infarction, hospitalization for unstable angina, and unplanned coronary revascularization) at 4.2 years in patients with any CAC and FFRCT > 0.80 vs. FFRCT ≤ 0.80 (3.9% and 8.7%, P = 0.04), however, in patients with CAC scores ≥400 the risk difference between groups did not reach statistical significance, 4.2% vs. 9.7% (P = 0.24). A negative relationship between CAC scores and FFRCT irrespective of stenosis severity was demonstrated. CONCLUSION:FFRCT shows promise in identifying patients with stenosis and calcification who can be managed without further downstream testing. Moreover, an inverse relationship between CAC levels and FFRCT was demonstrated. Studies are needed to further assess the clinical utility of FFRCT in patients with extensive coronary calcification.