Effect of Omega-3 Fatty Acids on Coronary Plaque Morphology　- A Serial Computed Tomography Angiography Study.

BACKGROUND: Omega-3 fatty acids have been proposed to be useful in the prevention of cardiac events. High-risk plaque (HRP) and plaque progression on serial coronary computed tomography angiography (CTA) have been suggested to be the predecessor of acute coronary syndrome (ACS). The purpose of this study was to investigate whether addition of omega-3 fatty acids to statin therapy for secondary prevention would lead to change in plaque characteristics detected by using serial CTA.Methods and Results: This study enrolled 210 patients with ACS: no eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA; EPA/DHA), low-dose EPA+DHA, high-dose EPA+DHA, and high-dose EPA alone. HRP was significantly more frequent in patients with plaque progression (P=0.0001). There was a significant interaction between plaque progression and EPA dose regardless of the DHA dose; 20.3% in EPA-none (no EPA/DHA), 15.7% in EPA-low (low-dose EPA+DHA), and 5.6% in EPA-high (high-dose EPA+DHA and high-dose EPA alone). On multivariate logistic regression analysis, HRP (OR 6.44, P<0.0001), EPA-high (OR 0.13, P=0.0004), and Rosvastatin (OR 0.24, P=0.0079) were the independent predictors for plaque progression. In quantitative analyses (n=563 plaques), the interval change of low attenuation plaque (LAP) volume was significantly different based on EPA dose; LAP was significantly increased in the EPA-none group and significantly decreased in the EPA-high group. CONCLUSIONS: In patients with ACS, addition of high-dose EPA (EPA-high) to statin therapy, compared to statin therapy without EPA, was associated with a lower rate of plaque progression.

Association of computed tomography-derived myocardial mass with fractional flow reserve-verified ischemia or subsequent therapeutic strategy.

The aim of the present study was to examine the association of myocardial mass verified by computed tomography (CT) and invasive fractional flow reserve (FFR)-verified myocardial ischemia, or subsequent therapeutic strategy for the targeted vessels after FFR examination. We examined 333 vessels with intermediate stenoses in 297 patients (mean age 69.0 ± 9.5, 228 men) undergoing both coronary CT angiography and invasive FFR, and reviewed the therapeutic strategy after FFR. Of 333 vessels, FFR ≤ 0.80 was documented in 130 (39.0%). Myocardial volume supplied by the target vessel (MVT) was larger in those with FFR-verified ischemia than those without (53.4 ± 19.5 vs. 42.9 ± 22.2 cm3, P < 0.001). Addition of MVT to a model including patient characteristics (age, gender), visual assessment (≥ 70% stenosis, high-risk appearance), and quantitative CT vessel parameters [minimal lumen area (MLA), plaque burden at MLA, percent aggregate plaque volume] improved C-index (from 0.745 to 0.778, P = 0.020). Furthermore, of 130 vessels with FFR ≤ 0.80, myocardial volume exposed to ischemia (MVI) was larger in the vessels with early revascularization after FFR examination than those without (37.2 ± 20.0 vs. 26.8 ± 15.0 cm3, P = 0.003), and was independently associated with early revascularization [OR = 1.03, 95% confidence interval (1.02-1.11), P < 0.001]. Using an on-site CT workstation, MVT identified coronary arteries with FFR-verified ischemia easily and non-invasively, and MVI was associated with subsequent therapeutic strategy after FFR examinations.

On-site assessment of computed tomography-derived fractional flow reserve in comparison with myocardial perfusion imaging and invasive fractional flow reserve.

Myocardial perfusion imaging (MPI) using Single Photon Emission Computed Tomography has been established as a standard noninvasive tool for risk stratification of coronary artery disease (CAD). We evaluated the diagnostic performance of on-site workstation-based computed tomography-derived fractional flow reserve (CT-FFR) in comparison with MPI using invasive fractional flow reserve (invasive FFR) as a gold standard. We enrolled 97 patients with suspected CAD. Diagnostic performance of CT angiography (CTA), and CT-FFR was compared in 105 lesions of 97 patients. Invasive FFR ≤ 0.8 was detected in 38 (36%) lesions. Diagnostic performance of CT-FFR was improved compared with CTA (AUC 0.83 vs. 0.60, p < 0.0001). The lesions with both CTA and MPI findings (n = 47), invasive FFR ≤ 0.8 was detected in 19 (40.4) lesions. CT-FFR (AUC 0.81, 95% CI 0.72-0.94) significantly improved diagnostic performance compared with CTA-50% (AUC 0.59, p = 0.00019) and MPI (AUC 0.64, p = 0.0082). In lesions with ≥ 50% on CTA (n = 42), diagnostic accuracy of CT-FFR (AUC 0.81) was significantly superior to MPI (AUC 0.64, p = 0.0239). In conclusions, CT-FFR improved diagnostic accuracy to detect invasive FFR ≤ 0.8 compared with luminal stenosis on CTA and ischemia on MPI. Patients with ≥ 50% stenosis on CTA would be the candidates for CT-FFR.

Ultra-High-Resolution Computed Tomography Angiography for Assessment of Coronary Artery Stenosis.

BACKGROUND: Limitations of coronary computed tomography (CTA) include false-positive stenosis at calcified lesions and assessment of in-stent patency. A prototype of ultra-high resolution computed tomography (U-HRCT: 1,792 channels and 0.25-mm slice thickness×128 rows) with improved spatial resolution was developed. We assessed the diagnostic accuracy of coronary artery stenosis using U-HRCT.Methods and Results:Seventy-nine consecutive patients who underwent CTA using U-HRCT were prospectively included. Coronary artery stenosis was graded from 0 (no plaque) to 5 (occlusion). Stenosis grading at 102 calcified lesions was compared between U-HRCT and conventional-resolution CT (CRCT: 896 channels and 0.5-mm slice thickness×320 rows). Median stenosis grading at calcified plaque was significantly improved on U-HRCT compared with CRCT (1; IQR, 1-2 vs. 2; IQR, 1-3, P<0.0001). Assessability of in-stent lumen was evaluated on U-HRCT in 79 stents. Stent strut thickness and luminal diameter were quantitatively compared between U-HRCT and CRCT. Of 79 stents, 83.5% were assessable on U-HRCT; 80% of stents with diameter 2.5 mm were regarded as assessable. On U-HRCT, stent struts were significantly thinner (median, 0.78 mm; IQR, 0.7-0.83 mm vs. 0.83 mm; IQR, 0.75-0.92 mm, P=0.0036), and in-stent lumens were significantly larger (median, 2.08 mm; IQR, 1.55-2.51 mm vs. 1.74 mm; IQR, 1.31-2.06 mm, P<0.0001) than on CRCT. CONCLUSIONS: U-HRCT with improved spatial resolution visualized calcified lesions with fewer artifacts. The in-stent lumen of stents with diameter ≥2.5 mm was assessable on U-HRCT.

Noninvasive Assessment of Stenotic Severity and Plaque Characteristics by Coronary CT Angiography in Patients Scheduled for Carotid Artery Revascularization.

AIMS: Coronary artery atherosclerosis in patients needing carotid revascularization has not been fully clarified. The aim of this study was to evaluate the stenotic severity and plaque characteristics of coronary arteries by coronary computed tomography angiography (CTA) in patients scheduled for carotid-artery stenting (CAS) or carotid endarterectomy (CEA). METHODS: We performed coronary CTA after carotid ultrasound (US) in 164 patients (81.7% male, aged 68.1± 12.2 years) from 2014 to 2016. Of all, 70 were scheduled for CAS or CEA (CAS/CEA group) and 94 were not (non-CAS/CEA group). Carotid US and coronary CTA were compared for the evaluation of stenotic severity and plaque characteristics of each vessel between CAS/CEA and non-CAS/CEA groups. RESULTS: Between the two groups, there were significant differences in the presence of significant stenosis (SS: ≥70% stenosis of coronary artery) (55.7% vs. 39.4%, P=0.038), triple-vessel disease (TVD)/left main trunk (LMT) (SS in each of three epicardial vessels and/or LMT) (24.3% vs. 7.5%, P= 0.0025), and high-risk plaque (HRP: positive remodeling and/or low attenuation) (55.7% vs. 24.5%, P＜0.0001). CAS/CEA was independently associated with TVD/LMT (OR=2.30, 95%CI: 1.14-8.59, P=0.026) and HRP (OR=3.17, 95%CI: 1.57-6.54, P=0.0012) in multivariable logistic regression analysis. Similarly, vulnerable plaque (78.6% vs. 2.1%, P＜0.0001) as well as severe stenosis of carotid artery (98.6% vs. 0%, P＜0.0001) was seen more often in CAS/CEA than in non-CAS/CEA group. CONCLUSIONS: The prevalence of TVD/LMT and HRP determined by coronary CTA is higher in patients needing CAS/CEA than in those without. Management of systemic atherosclerosis is required in the perioperative period of CAS/CEA.

Extracorporeal Shock Wave Therapy for Coronary Artery Disease: Relationship of Symptom Amelioration and Ischemia Improvement.

OBJECTIVES: The current management of coronary artery disease (CAD) relies on three major therapeutic options, namely medication, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). However, severe CAD that is not indicated for PCI or CABG still bears a poor prognosis due to the lack of effective treatments. In 2006, extracorporeal cardiac shock wave (SW) therapy reported on human for the first time. This treatment resulted in better myocardial perfusion as evaluated by dipyridamole stress thallium scintigraphy, angina symptoms, and exercise tolerance. The aim of the present study was to investigate: myocardial perfusion images and evaluate the relationship between the ischemia improvement and symptom amelioration by SW therapy. METHODS: We treated ten patients (i.e., nine males and one female) with cardiac SW therapy who had CAD but not indicated for PCI or CABG and aged 63-89 years old. After the SW therapy, all patients were followed up for three months to evaluate any amelioration of the myocardial ischemia based on symptoms, adenosine stress thallium scintigraphy, transthoracic echocardiography, and blood biochemical examinations. RESULTS: The changes in various parameters were evaluated before and after cardiac SW therapy. The cardiac SW therapy resulted in a significant improvement in the symptoms as evaluated by the Canadian Cardiovascular Society [CCS] class score (P=0.016) and a tendency to improve in summed stress score (SSS) (P=0.068). However, no significant improvement was observed in the summed rest score (SRS), summed difference score (SDS), left ventricular wall motion score index (LVWMSI), N-terminal pro-brain natriuretic, and troponin I. The difference of CCS class score (ΔCCS) was significantly correlated with those of SSS (ΔSSS) and SDS (ΔSDS) (r=0.69, P=0.028 and r=0.70, P=0.025, respectively). There was no significant correlation between ΔCCS and other parameters. Furthermore, no significant difference was observed between the CCS improved and non-improved groups in terms of the baseline characteristics. CONCLUSION: The current study demonstrated the potential efficacy and safety of Cardiac SW therapy in CAD patients. As the findings indicated, symptom amelioration was associated with ischemia improvement by extracorporeal shock wave therapy for the CAD patients.

Assessment of endothelial shear stress in patients with mild or intermediate coronary stenoses using coronary computed tomography angiography: comparison with invasive coronary angiography.

Characterization of endothelial shear stress (ESS) may allow for prediction of the progression of atherosclerosis. The aim of this investigation was to develop a non-invasive approach for in vivo assessment of ESS by coronary computed tomography angiography (CTA) and to compare it with ESS derived from invasive coronary angiography (ICA). A total of 41 patients with mild or intermediate coronary stenoses who underwent both CTA and ICA were included in the analysis. Two geometrical models of the interrogated vessels were reconstructed separately from CTA and ICA images. Subsequently, computational fluid dynamics were applied to calculate the ESS, from which ESSCTA and ESSICA were derived, respectively. Comparisons between ESSCTA and ESSICA were performed on 163 segments of 57 vessels in the CTA and ICA models. ESSCTA and ESSICA were similar: mean ESS: 4.97 (4.37-5.57) Pascal versus 4.86 (4.27-5.44) Pascal, p = 0.58; minimal ESS: 0.86 (0.67-1.05) Pascal versus 0.79 (0.63-0.95) Pascal, p = 0.37; and maximal ESS: 14.50 (12.62-16.38) Pascal versus 13.76 (11.44-16.08) Pascal, p = 0.44. Good correlations between the ESSCTA and the ESSICA were observed for the mean (r = 0.75, p < 0.001), minimal (r = 0.61, p < 0.001), and maximal (r = 0.62, p < 0.001) ESS values. In conclusion, geometrical reconstruction by CTA yields similar results to ICA in terms of segment-based ESS calculation in patients with low and intermediate stenoses. Thus, it has the potential of allowing combined local hemodynamic and plaque morphologic information for risk stratification in patients with coronary artery disease.

Eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio as an associated factor of high risk plaque on coronary computed tomography in patients without coronary artery disease.

BACKGROUND AND AIMS: Coronary computed tomography angiography (CCTA)-verified high risk plaque (HRP) characteristics including positive remodeling and low attenuation plaque have been associated with acute coronary syndromes. Several studies reported that the n-3 polyunsaturated fatty acids have been associated with cardiovascular events. However, the relationship between serum eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio and CCTA-verified HRP in patients without known coronary artery disease (CAD) is unclear. We aimed at investigating the relation between EPA/AA and CCTA-verified HRP in patients without known CAD. METHODS: We included 193 patients undergoing CCTA without known CAD (65.5 ± 12.0 years, 55.0% male). No patient has been treated with EPA. The relation of coronary risk factors, lipid profile, high-sensitivity C-reactive protein, coronary artery calcification score (CACS), number of vessel disease, plaque burden, and EPA/AA with the presence of HRP was evaluated by logistic regression analysis. Incremental value of EPA/AA to predict HRP was also analyzed by C-index, NRI, and IDI. A Cox proportional hazards model was used to estimate the time to cardiovascular event. RESULTS: HRP was observed in 37 (19%) patients. Multivariable logistic regression analysis revealed that current smoking (OR 2.58; p=0.046), number of vessel disease (OR 1.87; p=0.031), and EPA/AA ratio (OR 0.65; p=0.0006) were independent associated factors of HRP on CCTA. Although the addition of EPA/AA to the baseline model did not significantly improve C-index, both NRI (0.60, p=0.0049) and IDI (0.054, p=0.0072) were significantly improved. Patients with HRP had significantly higher rate of events compared with patients without HRP (14% vs. 3%, Logrank p=0.0004). On multivariable Cox hazard analysis, baseline EPA/AA ratio was an independent predictor (HR 0.57, p=0.047). CONCLUSIONS: Low EPA/AA was an associated factor of HRP on CCTA in patients without CAD. In addition to conventional coronary risk factors and CACS, EPA/AA and CCTA might be useful for risk stratification of CAD.

The impact of image resolution on computation of fractional flow reserve: coronary computed tomography angiography versus 3-dimensional quantitative coronary angiography.

Calculation of fractional flow reserve (FFR) based on computational fluid dynamics (CFD) requires reconstruction of patient-specific coronary geometry and estimation of hyperemic flow rate. Coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) are two dominating imaging modalities used for the geometrical reconstruction. Our aim was to investigate the impact of image resolution as inherently associated with these two imaging modalities on geometrical reconstruction and subsequent FFR calculation. Patients with mild or intermediate coronary stenoses who underwent both CCTA and ICA were included. CCTA images were acquired either by 320-row area detector CT or by 128-slice dual-source CT. Two geometrical models were reconstructed separately from CCTA and ICA, from which FFRCTA and FFRQCA were subsequently calculated using CFD simulations, applying the same hyperemic flow rate derived from the ICA images at the inlet boundaries. A total of 57 vessels in 41 patients were analyzed. Average diameter stenosis was 43.4 ± 10.8 % by 3D QCA. Reasonably good correlation between FFRCTA and FFRQCA was observed (r = 0.71, p < 0.001). The difference between FFRCTA and FFRQCA was correlated with the deviation between minimal lumen areas by CCTA and by ICA (ρ = 0.34, p = 0.01), but not with plaque volume (ρ = -0.09, p = 0.51) or calcified plaque volume (ρ = 0.01, p = 0.95). Applying the cutoff value of ≤0.8 to both FFRCTA and FFRQCA, the agreement between FFRCTA and FFRQCA in discriminating functional significant stenoses was moderate (kappa 0.47, p < 0.001). Disagreement was found in 10 (17.5 %) vessels. Acceptable correlation between FFRCTA and FFRQCA was observed, while their agreement in distinguishing functional significant stenosis was moderate. Our results suggest that image resolution has a significant impact on FFR computation.

Plaque Characterization by Coronary Computed Tomography Angiography and the Likelihood of Acute Coronary Events in Mid-Term Follow-Up.

BACKGROUND: Coronary computed tomography angiography (CTA)-verified positive remodeling and low attenuation plaques are considered morphological characteristics of high-risk plaque (HRP) and predict short-term risk of acute coronary syndrome (ACS). OBJECTIVES: This study evaluated whether plaque characteristics by CTA predict mid-term likelihood of ACS. METHODS: The presence of HRP and significant stenosis (SS) of ≥70% were evaluated in 3,158 patients undergoing CTA. Serial CTA was performed in 449 patients, and plaque progression (PP) was evaluated. Outcomes (fatal and nonfatal ACS) were recorded during follow-up (mean 3.9 ± 2.4 years). RESULTS: ACS occurred in 88 (2.8%) patients: 48 (16.3%) of 294 HRP(+) and 40 (1.4%) of 2,864 HRP(-) patients. ACS was also significantly more frequent in SS(+) (36 of 659; 5.5%) than SS(-) patients (52 of 2,499; 2.1%). HRP(+)/SS(+) (19%) and HRP(+)/SS(-) (15%) had higher rates of ACS compared with no-plaque patients (0.6%). Although ACS incidence was relatively low in HRP(-) patients, the cumulative number of patients with ACS developing from HRP(-) lesions (n = 43) was similar to ACS patients with HRP(+) lesions (n = 45). In patients with serial CTA, PP also was an independent predictor of ACS, with HRP (27%; p < 0.0001) and without HRP (10%) compared with HRP(-)/PP(-) patients (0.3%). CONCLUSIONS: CTA-verified HRP was an independent predictor of ACS. However, the cumulative number of ACS patients with HRP(-) was similar to patients with HRP(+). Additionally, plaque progression detected by serial CTA was an independent predictor of ACS.