Percent Atheroma Volume Research Articles

Wall shear stress-related plaque growth of lipid-rich plaques in human coronary arteries: an near-infrared spectroscopy and optical coherence tomography study.

Low wall shear stress (WSS) is acknowledged to play a role in plaque development through its influence on local endothelial function. Also, lipid-rich plaques (LRPs) are associated with endothelial dysfunction. However, little is known about the interplay between WSS and the presence of lipids with respect to plaque progression. Therefore, we aimed to study the differences in WSS-related plaque progression between LRPs, non-LRPs, or plaque-free regions in human coronary arteries. In the present single-centre, prospective study, 40 patients who presented with an acute coronary syndrome successfully underwent near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) and optical coherence tomography (OCT) of at least one non-culprit vessel at baseline and completed a 1-year follow-up. WSS was computed applying computational fluid dynamics to a three-dimensional reconstruction of the coronary artery based on the fusion of the IVUS-segmented lumen with a CT-derived centreline, using invasive flow measurements as boundary conditions. For data analysis, each artery was divided into 1.5 mm/45° sectors. Plaque growth based on IVUS-derived percentage atheroma volume change was compared between LRPs, non-LRPs, and plaque-free wall segments, as assessed by both OCT and NIRS. Both NIRS- and OCT-detected lipid-rich sectors showed a significantly higher plaque progression than non-LRPs or plaque-free regions. Exposure to low WSS was associated with a higher plaque progression than exposure to mid or high WSS, even in the regions classified as a plaque-free wall. Furthermore, low WSS and the presence of lipids had a synergistic effect on plaque growth, resulting in the highest plaque progression in lipid-rich regions exposed to low shear stress. This study demonstrates that NIRS- and OCT-detected lipid-rich regions exposed to low WSS are subject to enhanced plaque growth over a 1-year follow-up. The presence of lipids and low WSS proves to have a synergistic effect on plaque growth.

Clinical and Coronary Plaque Predictors of Atherosclerotic Nonresponse to Statin Therapy

BackgroundStatins reduce the incidence of major cardiovascular events, but residual risk remains. The study examined the determinants of atherosclerotic statin nonresponse. ObjectivesThis study aimed to investigate factors associated with statin nonresponse-defined atherosclerosis progression in patients treated with statins. MethodsThe multicenter PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) registry included patients who underwent serial coronary computed tomography angiography ≥2 years apart, with whole-heart coronary tree quantification of vessel, lumen, and plaque, and matching of baseline and follow-up coronary segments and lesions. Patients with statin use at baseline and follow-up coronary computed tomography angiography were included. Atherosclerotic statin nonresponse was defined as an absolute increase in percent atheroma volume (PAV) of 1.0% or more per year. Furthermore, a secondary endpoint was defined by the additional requirement of progression of low-attenuation plaque or fibro-fatty plaque. ResultsThe authors included 649 patients (age 62.0 ± 9.0 years, 63.5% male) on statin therapy and 205 (31.5%) experienced atherosclerotic statin nonresponse. Age, diabetes, hypertension, and all atherosclerotic plaque features measured at baseline scan (high-risk plaque [HRP] features, calcified and noncalcified PAV, and lumen volume) were significantly different between patients with and without atherosclerotic statin nonresponse, whereas only diabetes, number of HRP features, and noncalcified and calcified PAV were independently associated with atherosclerotic statin nonresponse (odds ratio [OR]: 1.41 [95% CI: 0.95-2.11], OR: 1.15 [95% CI: 1.09-1.21], OR: 1.06 [95% CI: 1.02-1.10], OR: 1.07 [95% CI: 1.03-1.12], respectively). For the secondary endpoint (N = 125, 19.2%), only noncalcified PAV and number of HRP features were the independent determinants (OR: 1.08 [95% CI: 1.03-1.13] and OR: 1.21 [95% CI: 1.06-1.21], respectively). ConclusionsIn patients treated with statins, baseline plaque characterization by plaque burden and HRP is associated with atherosclerotic statin nonresponse. Patients with the highest plaque burden including HRP were at highest risk for plaque progression, despite statin therapy. These patients may need additional therapies for further risk reduction.

Glycemic control is independently associated with rapid progression of coronary atherosclerosis in the absence of a baseline coronary plaque burden: a retrospective case–control study from the PARADIGM registry

BackgroundThe baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the absence of a baseline coronary plaque burden are limited. Thus, this study aimed to investigate the predictors for RPP in patients without coronary plaques on baseline coronary computed tomography angiography (CCTA) images.MethodsA total of 402 patients (mean age: 57.6 ± 10.0 years, 49.3% men) without coronary plaques at baseline who underwent serial coronary CCTA were identified from the Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry and included in this retrospective study. RPP was defined as an annual change of ≥ 1.0%/year in the percentage atheroma volume (PAV).ResultsDuring a median inter-scan period of 3.6 years (interquartile range: 2.7–5.0 years), newly developed coronary plaques and RPP were observed in 35.6% and 4.2% of the patients, respectively. The baseline traditional risk factors, i.e., advanced age (≥ 60 years), male sex, hypertension, diabetes mellitus, hyperlipidemia, obesity, and current smoking status, were not significantly associated with the risk of RPP. Multivariate linear regression analysis showed that the serum hemoglobin A1c level (per 1% increase) measured at follow-up CCTA was independently associated with the annual change in the PAV (β: 0.098, 95% confidence interval [CI]: 0.048–0.149; P < 0.001). The multiple logistic regression models showed that the serum hemoglobin A1c level had an independent and positive association with the risk of RPP. The optimal predictive cut-off value of the hemoglobin A1c level for RPP was 7.05% (sensitivity: 80.0%, specificity: 86.7%; area under curve: 0.816 [95% CI: 0.574–0.999]; P = 0.017).ConclusionIn this retrospective case–control study, the glycemic control status was strongly associated with the risk of RPP in patients without a baseline coronary plaque burden. This suggests that regular monitoring of the glycemic control status might be helpful for preventing the rapid progression of coronary atherosclerosis irrespective of the baseline risk factors. Further randomized investigations are necessary to confirm the results of our study.Trial registrationClinicalTrials.gov NCT02803411.

Abstract 10602: The Relationship Between Layered Plaque and Plaque Volume in Patients With Acute Coronary Syndromes

Introduction: Layered plaque is a signature of previous subclinical plaque destabilization and healing, which can be identified by optical coherence tomography (OCT). Silent plaque rupture or erosion with formation of a layer might contribute to rapid step-wise progression of plaque. We examined the relationship between layered plaques detected by OCT and plaque burden detected by intravascular ultrasound (IVUS) in patients with acute coronary syndromes (ACS). Methods: Patients presented with ACS who underwent preintervention OCT and IVUS were included in the analysis. Layered plaque was identified by OCT, and plaque burden was measured by IVUS around the culprit lesion. IVUS findings were compared between patients with layered plaque versus those without layered plaque. Results: Among 150 patients, total atheroma volume (TAV) (183.27 mm 3 [114.2 mm 3 to 275.0 mm 3 ] vs. 119.27 mm 3 [68.9 mm 3 to 185.5 mm 3 ], p=0.004), percent atheroma volume (PAV) (60.06 % [54.7 % to 60.1 %] vs. 53.69 % [46.8 % to 60.6 %], p=0.001), and plaque burden (PB) (86.51 % [81.7 % to 85.7 %] vs. 82.58 % [77.9 % to 85.4 %], p=0.001) were significantly higher in patients with layered plaques than non-layered plaques (Figure). When multi, single, and non-layered plaques were compared, TAV (188.69 mm 3 [122.1 mm 3 to 293.6 mm 3 ] vs. 137.85 mm 3 [100.1 mm 3 to 208.4 mm 3 ] vs. 119.27 mm 3 [68.9 mm 3 to 185.5 mm 3 ], p=0.021), PAV (62.12 % [56.8 % to 67.8 %] vs. 57.52 % [48.9 % to 60.1 %] vs. 53.69 % [46.8 % to 60.6 %] p&lt;0.001), and PB (87.44 % [81.8 % to 89.3 %] vs. 84.7 % [77.9 % to 88.0 %] vs. 82.58 % [77.9 % to 85.4 %], p=0.018) were significantly greater in multi-layered plaques than others. Conclusions: This study demonstrates that layered plaques, compared to non-layered plaques, have significantly greater plaque burden in patients with ACS, indicating plaque disruption and healing process, rather than gradual smooth muscle proliferation, significantly contributes to plaque progression at the culprit lesion in patients with ACS.

Abstract 12657: Clinical, Laboratory, and Coronary Plaque Predictors of Atherosclerotic Non-Response to Statin Therapy

Introduction: Statins reduce major cardiovascular events, but residual risk remains. The study examined determinants of atherosclerotic statin non-response in patients using statins. Hypothesis: We hypothesized that a comprehensive evaluation of atherosclerosis identifies patients that progress atherosclerosis despite the use of statin therapy. Methods: The multi-center PARADIGM registry included patients who underwent serial CCTA ≥2 years apart, with whole-heart coronary tree quantification of vessel, lumen and plaque, and matching of baseline and follow-up coronary segments and lesions. Patients with statin use at baseline and follow-up CCTA were included. Atherosclerotic statin non-response was defined as an absolute increase in percent atheroma volume (PAV) of 1.0% or more per year. A secondary endpoint was defined by the additional requirement of progression of low-attenuation plaque or fibro-fatty plaque. Results: We included 649 patients (62.0±9.0 years, 63.5% male) on statin therapy and 205 (31.5%) experienced atherosclerotic statin non-response. Age, diabetes, hypertension, and all atherosclerotic plaque features (high risk plaque [HRP] features, calcified and noncalcified PAV, and lumen volume) were significantly different between patients with and without atherosclerotic statin non response, while only diabetes, the number of high risk plaque features, noncalcified and calcified PAV were independently associated with atherosclerotic statin non-response (OR:1.41 (0.95-2.11), OR:1.15 (1.09-1.21), OR:1.06 (1.02-1.10), OR:1.07 (1.03-1.12), respectively). For the secondary endpoint (N=125, 19.2%), only non-calcified PAV and number of HRP features were the independent determinants (OR:1.08 (1.03-1.13) and OR:1.21 (1.06-1.21), respectively). Conclusions: In patients treated with statins, baseline plaque characterization by plaque burden and high risk plaque is associated with atherosclerotic statin non-response defined as important progression of coronary atherosclerosis. Patients with the highest plaque burden including HRP were at highest risk for plaque progression, despite statin therapy. These patients may need additional therapies for further risk reduction.

Abstract 15480: Liraglutide Inhibits Atherosclerotic Plaque Progression in Rabbits Through the Downregulation of Multiple Inflammatory and Metabolic Pathways

Background: Liraglutide, a GLP-1- receptor agonists approved for the treatment of type 2 diabetes and obesity confers a lower CVD mortality. However, mechanisms underlying this finding remain unknown, particularly in normoglycemic subjects. We investigated the effects of liraglutide on the progression and pathobiology of atherosclerosis using multimodal intravascular imaging in rabbits. Methods: Rabbits atherosclerosis (N=16) were induced by balloon injury of the abdominal aorta and cholesterol feeding for 6 weeks. Then, rabbits were imaged with intravascular ultrasound (IVUS) and near-infrared fluorescence optical coherence tomography (NIRF-OCT) for the analysis of plaque burden and plaque inflammation (ProSense VM110 NIRF agent, 4 mg/kg/iv) respectively. Next, rabbits were randomized into: Control (n=8) or liraglutide (n=8, 0.1 mg/kg/day) groups. Imaging was repeated after 4 weeks, followed by histopathology and RNA analysis. On per-slice basis (every 0.4 mm) of IVUS imaging, the percent atheroma volume (PAV) was measured across the 40 mm balloon injured area. Atheroma progression was quantified as the ΔPAV between 6 and 10 weeks. Results: IVUS analyses (3200 slices/16 rabbits) revealed that liraglutide significantly reduced plaque progression (ΔPAV, 1.5% [0.2-2.8] vs. 9.3% [6.7-13.0] control, p=0.05). In vivo distance-corrected VM110 cathepsin inflammatory plaque activity was similar (ΔNIRF average plaque 25.2 [-9.8- 62] vs. 22.6 [3.9- 52.5] nM control, p=0.72). Plaques from liraglutide-treated animals however exhibited fewer RAM11+ macrophages (21.3±11.4 vs. control 30.9±16.7 macrophages/section, p=0.01) stry. Both plaques showed similar αSMA (45.2±6.7% vs 52.4±1.2% αSMA+ area/section, p=0.327). Liraglutide decreased inflammatory RNA transcripts (IL-6 and TNF-α), and RNA-seq transcriptomic analysis revealed that liraglutide altered inflammatory and metabolic pathways (as CRP, CYP3A6, Apo-A4 and FMO3). Blood glucose was normal and similar between groups (p&gt;0.05). Conclusion: Liraglutide suppresses in vivo atherosclerotic plaque progression and plaque macrophage expression in normoglycemic rabbits. Further investigation of its plaque stabilizing effects in subjects with and without diabetes is warranted.

Abstract 9401: Impact of Visceral Abdominal Tissue on Coronary Artery Disease as Defined by Quantitative Computed Tomographic Angiography

Introduction: Obesity has long been associated with all-cause mortality and cardiovascular disease (CVD). Visceral abdominal tissue (VAT) has been proposed as an important CVD risk stratification metric and has been shown to correlate with the extent and severity of coronary artery plaque. This study aims to clarify the relationship between the presence and severity of VAT with the presence and severity of coronary artery plaque as defined by total plaque volume (TPV), calcified plaque (CP) volume, non-calcified plaque (NCP) volume, and high risk low-density non-calcified plaque (LD-NCP) using quantitative coronary computed tomography atherosclerosis imaging (AI-QCT). Methods: We reviewed 145 consecutive patients who had undergone CCTA and CT visceral fat analysis for health screening purposes. Atherosclerosis imaging - quantitative computed tomography (AI-QCT) was performed for TPV, percent atheroma volume (PAV), and the presence of stenosis. We segmented atherosclerosis by composition for CP, NCP and LD-NCP. Results: The mean age of the patients was 56.1 ± 8.5 years, 84.0% male. Overall, 3.5% had a history of diabetes, 19% hypertension, 38% dyslipidemia, 8% current smokers, and 34% had a family history of CAD. There was a stepwise progression of the median coronary plaque volume for each quartile of visceral fat including total plaque volume (Q1: 19.8, Q2: 48.1, Q3: 86.4, and Q4: 136.6 mm 3 (P=0.0098)), NCP (Q1: 15.7, Q2: 35.4, Q3: 86.4, and Q4: 136.6 mm 3 (P=0.0032)) and LD-NCP (Q1: 0.6, Q2: 0.81, Q3: 2.0, and Q4: 5.0 mm 3 (P&lt;0.0001)). Conclusion: Our findings represent the first demonstration of a stepwise progression with regards to visceral abdominal tissue and total plaque volume, non-calcified plaque volume, and, particularly of note, low density non-calcified plaque volume. A stepwise progression as demonstrated here may indicate the future usefulness of VAT in CVD risk stratification and its role in longitudinal preventive care.

Abstract 12773: Computed Tomography Angiography Evaluation of Coronary Plaque Burden in South Asians and Non-Hispanic Whites Over 65 Years of Age

Introduction: South Asians (SA) have greater atherosclerotic cardiovascular disease (ASCVD) rates than non-Hispanic whites (NHW). SA ethnicity is a risk factor for cardiovascular disease, according to ACC/AHA guidelines. However, data on pattern of atherosclerosis in SA is limited. This study examines plaque burden in SA using quantitative plaque analysis from coronary CT angiography (CCTA). Methods: This is a cross-sectional study comparing the prevalence of atherosclerosis in SA to that of NHW. We identified 104 South Asians who underwent CCTA and quantitative plaque analysis. We then matched 1:1 with 104 non-Hispanic whites. Age, gender, diabetes, hypertension and smoking were utilized to perform a 1: 1 covariate match. Quantification of coronary plaque was conducted using automated plaque analysis software (Cleerly, NY, NY). Percentage atheroma volume (PAV), which is a measure of total plaque divided by total vessel volume, was calculated for each plaque subtypes. Results: A total of 208 subjects formed the study population. The mean age was 71.2±4.9, 66% being male, 38% had DM, 72% reported hypertension, and 10% were past smokers in each group. The SA cohort had significantly higher calcified plaque PAV compared to NHW cohort, median (IQR), 7.6(1.9, 15.5) versus 3.9(1.3, 9.6), (p=0.027). Noncalcified plaque PAV was higher in SA 5.2 (3.0, 7.9) versus 4.5 (2.6,7.2), but not statistically significant (p=0.35). The number of subjects with obstructive disease (&amp;gt50% stenosis) trended higher in the SA cohort (71% of SA versus 60% of NHW) (p=0.08). Conclusions: South Asians had significantly higher calcified plaque PAV and a higher prevalence of obstructive disease compared to the NHW cohort. These results are suggestive of a unique plaque burden and distinctive characteristics in the SA population, which may explain the greater incidence of cardiovascular events and supports the current guidelines.

Abstract 10740: Effects of Renin-Angiotensin-Aldosterone-System Inhibitors on Coronary Atherosclerotic Plaques: Results From the Paradigm Registry

Introduction: Coronary CT Angiogram (CCTA) has become a powerful tool in the diagnosis and risk stratification of coronary artery disease (CAD), but can also provide unique insight into the effects of pharmacotherapy on the progression of atherosclerosis. Although Renin-Angiotensin-Aldosterone-System (RAAS) inhibitors are indicated in patients with stable CAD, their impact on the progression of coronary atherosclerosis is unclear. Methods: We performed a prospective, multinational study consisting of a registry of patients without history of CAD who underwent serial CCTAs at an interscan interval of &gt;2 years. Patients taking RAAS inhibitors were propensity matched to RAAS inhibitor naïve patients based on clinical and CCTA characteristics at the baseline. Atherosclerotic plaques in CCTAs were quantitatively analyzed for percent atheroma volume (PAV) according to plaque composition (necrotic core, fibro-fatty plaque, fibrous plaque, and calcium) using predefined Hounsfield unit thresholds. Results: Of 1,248 patients from the registry, 299 RAAS inhibitor taking patients were matched to 299 RAAS inhibitor naïve patients. Over a median interval of 3.9 years, there was no significant difference in annual progression of total PAV between RAAS inhibitor naive vs taking patients (0.75 vs 0.79 %/year, p = 0.66), nor was there any difference in the progression of necrotic core (-0.02 vs 0.002 %/year, p = 0.09), fibrofatty plaque (-0.03 vs.0.05 %/year, p = 0.67), fibrous plaque (0.29 vs 0.25 %/year, p =0.91), or calcified plaque (0.51 vs. 0.51 %/year, p = 0.37). Conclusions: Within this cohort of patients, the use of RAAS inhibitors over a period of nearly 4 years did not have a measurable impact on progression of total atherosclerotic plaque or any plaque subtypes assessed by CCTA. These results suggest that the benefit of RAAS inhibition is independent of an effect on coronary plaque progression.

Effect of Atorvastatin on Serial Changesin Coronary Physiology andPlaque Parameters.

The effects of statin on coronary physiology have not been well evaluated. The authors performed this prospective study to investigate changes in coronary flow indexes and plaque parameters, and their associations with atorvastatin therapy in patients with coronary artery disease (CAD). Ninety-five patients with intermediate CAD who received atorvastatin therapy underwent comprehensive physiological assessments with fractional flow reserve (FFR), coronary flow reserve, index of microcirculatory resistance, and intravascular ultrasound at the index procedure, and underwent the same evaluations at 12-month follow-up. Optimal low-density lipoprotein cholesterol (LDL-C) was defined as LDL-C<70mg/dL or≥50% reduction from the baseline. The primary endpoint was a change in the FFR. Baseline FFR, minimal lumen area, and percent atheroma volume (PAV) were 0.88 ± 0.05, 3.87 ± 1.28, 55.92 ± 7.30, respectively. During 12months, the percent change in LDL-C was -33.2%, whereas FFR was unchanged (0.87 ± 0.06 at 12months; P=0.694). Vessel area, lumen area, and PAV were significantly decreased (all P values<0.05). The achieved LDL-C level and the change of PAV showed significant inverse correlations with the change in FFR. In patients with optimally modified LDL-C, the FFR had increased (0.87 ± 0.06 vs 0.89 ± 0.07; P=0.014) and the PAV decreased (56.81 ± 6.44% vs 55.18 ± 8.19%; P=0.031), whereas in all other patients, the FFR had decreased (0.88 ± 0.05 vs 0.86 ± 0.06; P=0.025) and the PAV remained unchanged. In patients with CAD, atorvastatin did not change FFR despite a decrease in the PAV. However, in patients who achieved the optimal LDL-C target level with atorvastatin, the FFR had significantly increased with decrease of the PAV. (Effect of Atorvastatin on Fractional Flow Reserve in Coronary Artery Disease [FORTE]; NCT01946815).

Interrelation between baseline plaque characteristics and changes in coronary atherosclerosis with the PCSK9-inhibitor alirocumab: insights from the PACMAN-AMI randomized trial

Abstract Background Patients with acute myocardial infarction (AMI) frequently experience recurrent atherothrombotic events, largely attributable to non-culprit lesions with high-risk characteristics. Statins can halt the progression of coronary atherosclerosis, and addition of protein convertase subtilisin/kexin type 9-inhibitors (PCSK9i) results in incremental low-density lipoprotein cholesterol (LDL-C) lowering and atheroma regression. Purpose We sought to examine the interrelation between baseline imaging characteristics, on-treatment LDL-C levels, and changes in coronary atherosclerosis as assessed by serial, multi-modality intracoronary imaging in patients with AMI. Methods This is a post hoc analysis from the PACMAN-AMI randomized trial. Patients were randomly allocated to biweekly alirocumab 150 mg vs. placebo on top of high-intensity statin initiated within 24h of presentation with AMI, and underwent serial imaging of the two non-infarct-related arteries at baseline and after 52 weeks. The primary endpoint was percent atheroma volume (PAV) by intravascular ultrasound (IVUS). Powered secondary endpoints were maximal lipid core burden index (maxLCBI4mm) by near-infrared spectroscopy (NIRS) and minimum fibrous cap thickness (FCTmin) by optical coherence tomography (OCT). Results Of 300 randomized patients (mean age 58.5±9.8 years, 18.7% women, baseline LDL-C 3.94±0.87 mmol/L), IVUS was serially performed in 265 patients (537 arteries). LDL-C levels decreased to 1.92±0.79 mmol/L with placebo and 0.61±0.61 mmol/L with alirocumab (p&amp;lt;0.001). Compared with placebo (statin alone), alirocumab added to statin resulted in greater PAV reduction (−2.13% vs. −0.92%; p&amp;lt;0.001), greater maxLCBI4mm reduction (−79.42 vs. −37.60; p=0.006), and greater increase in FCTmin (62.67 vs. 33.19 μm; p=0.001). Changes in PAV and maxLCBI4mm were inversely related to on-treatment LDL-C levels, and change in FCTmin was positively related to on-treatment LDL-C levels (Figure 1). Across all patients, we found significant, inverse relationships between change in PAV and baseline PAV [slope: −0.072 (95% CI −0.101 to −0.042); p&amp;lt;0.001], between change in maxLCBI4mm and baseline maxLCBI4mm [slope: −0.437 (95% CI −0.505 to −0.369); p&amp;lt;0.001], and between change in FCTmin and baseline FCTmin [slope: −0.436 (95% CI −0.541 to −0.332); p&amp;lt;0.001]; these findings indicate greater PAV and maxLCBI4mm regression in lesions with greater PAV and LCBI4mm at baseline, and greater fibrous cap thickening in lesions with thinner fibrous caps at baseline. Conclusion In this study of intensive LDL-C lowering treatment initiated in the acute AMI setting, more favorable plaque changes were observed in patients with lower on-treatment LDL-C levels and in lesions with more adverse baseline plaque characteristics. Whether AMI patients with high-risk plaque features might derive greater clinical benefit from early initiation of intensive LDL-C-lowering therapies requires further investigation. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sanofi, Regeneron

Artificial intelligence-enabled comprehensive coronary phenotyping in patients with suspected CAD

Abstract Introduction The capabilities of artificial intelligence (AI) are rapidly progressing and the research community is getting increasingly interested in its possibilities. AI algorithms are able to work continuously and at high speed, reducing human workload and saving time that physicians can spend on more complex data or rarer cases. However, many clinical AI applications are currently only used in a research setting and lack proper testing and validation. Objectives This study aimed to determine the accuracy and performance of a novel AI-based software tool for CCTA analysis compared to conventional expert evaluation. Methods We evaluated 100 CCTA exams from a cohort of symptomatic patients with mild-to-moderately abnormal non-invasive ischemia test. Stenosis severity assessed by AI-based analysis (automatic evaluation, AEv) was compared with a level III expert CCTA interpretation (manual evaluation, MEv). AI-based analysis reported exact % stenosis and obstructive CAD was considered if maximal stenosis was ≥50%. Plaque phenotype was also estimated using AI algorithms. Results The study cohort was as follows: 52% male, mean age 68±10 years. The prevalence of hypertension, dyslipidemia and diabetes was 77%, 81% and 23%, respectively, and 10-year cardiovascular risk was 19±10% as predicted by Framingham risk score. Typical angina was present in 33%, of which 67% had a Canadian Cardiovascular Society angina grade ≥2. Overall prevalence of obstructive CAD determined by MEv and AEv was 25% and 21%, respectively, with a significant association between both assessments (p&amp;lt;0.001). When compared to MEv as reference, AEv method performed with a sensitivity, specificity, positive and negative predictive values of 0.56, 0.91, 0.58 and 0.86, respectively. Area under the curve was 0.871 (p&amp;lt;0.001) demonstrating high accuracy. AEv atherosclerosis quantification revealed significant differences between patients with and without obstructive CAD according to MEv: median total plaque volume (569 vs 115 mm3, p&amp;lt;0.001), calcified plaque volume (297 vs 19 mm3, p&amp;lt;0.001), non-calcified plaque volume (235 vs 71 mm, p&amp;lt;0.001), low-density non-calcified plaque volume (2.8 vs 1.0 mm3, p=0.023) and percent atheroma volume (16.1 vs 3.8 mm3, p&amp;lt;0.001). Conclusion In patients with suspected CAD and mild-to-moderately abnormal ischemia tests, a diagnostic strategy using AEv as a gatekeeper is effective, providing a quantitative stenosis evaluation with similar diagnostic performance for obstructive CAD when compared to MEv. AI-enabled approach additionally allows a fully automated quantification of coronary plaque volumes and composition, which would further enhance risk stratification. Funding Acknowledgement Type of funding sources: None.

Implications of computed tomography reconstruction algorithms on coronary atheroma quantification: Comparison with intravascular ultrasound

BackgroundAdvances in coronary computed tomography angiography (CCTA) reconstruction algorithms are expected to enhance the accuracy of CCTA plaque quantification. We aim to evaluate different CCTA reconstruction approaches in assessing vessel characteristics in coronary atheroma using intravascular ultrasound (IVUS) as the reference standard. MethodsMatched cross-sections (n ​= ​7241) from 50 vessels in 15 participants with chronic coronary syndrome who prospectively underwent CCTA and 3-vessel near-infrared spectroscopy-IVUS were included. Twelve CCTA datasets per patient were reconstructed using two different kernels, two slice thicknesses (0.75 ​mm and 0.50 ​mm) and three different strengths of advanced model-based iterative reconstruction (IR) algorithms. Lumen and vessel wall borders were manually annotated in every IVUS and CCTA cross-section which were co-registered using dedicated software. Image quality was sub-optimal in the reconstructions with a sharper kernel, so these were excluded. Intraclass correlation coefficient (ICC) and repeatability coefficient (RC) were used to compare the estimations of the 6 CT reconstruction approaches with those derived by IVUS. ResultsSegment-level analysis showed good agreement between CCTA and IVUS for assessing atheroma volume with approach 0.50/5 (slice thickness 0.50 ​mm and highest strength 5 ADMIRE IR) being the best (total atheroma volume ICC: 0.91, RC: 0.67, p ​< ​0.001 and percentage atheroma volume ICC: 0.64, RC: 14.06, p ​< ​0.001). At lesion-level, there was no difference between the CCTA reconstructions for detecting plaques (accuracy range: 0.64–0.67; p ​= ​0.23); however, approach 0.50/5 was superior in assessing IVUS-derived lesion characteristics associated with plaque vulnerability (minimum lumen area ICC: 0.64, RC: 1.31, p ​< ​0.001 and plaque burden ICC: 0.45, RC: 32.0, p ​< ​0.001). ConclusionCCTA reconstruction with thinner slice thickness, smooth kernel and highest strength advanced IR enabled more accurate quantification of the lumen and plaque at a segment-, and lesion-level analysis in coronary atheroma when validated against intravascular ultrasound. Clinicaltrials.gov (NCT03556644)

Dynamic natural morphologies and component changes in nonculprit subclinical atherosclerosis in patients with acute coronary syndrome at 1-year follow-up and clinical significance at 3-year follow-up

Background and aimsWe aimed to explore the dynamic natural morphologies and main components of nonculprit subclinical atherosclerotic changes underlying lesion regression (LR) or lesion progression (LP) in patients with acute coronary syndrome. MethodsThe primary endpoints were changes in percent atheroma volume (ΔPAV), normalized total atheroma volume (ΔTAVn) and each component in nonculprit subclinical atherosclerosis from baseline to 1 year measured by optical flow ratio (OFR) software. LR or LP was defined by an increase or decrease in PAV. Secondary endpoints included the correlation between changes in the lipid profile and ΔPAV/ΔTAVn and major adverse cardiac events (MACEs) related to nonculprit subclinical atherosclerosis at 3 years. ResultsThis was a subgroup analysis of our previous randomized trial with a total of 161 nonculprit lesions analysed. In the LR (approximately 55.3% of the lesions) group, ΔTAVn was positively correlated only with lipid ΔTAVn (r = 0.482, p < 0.001) but not fibrous and calcium ΔTAVn, and ΔPAV was positively correlated with lipid ΔPAV (r = 0.315, p = 0.003) but not fibrous and calcium ΔPAV. The percent reduction in low-density lipoprotein cholesterol (LDL-C) was an independent predictor of LR in multivariate logistic regression analysis (OR = 3.574, 95% CI: 1.125–11.347, p = 0.031). The incidence of MACEs related to nonculprit lesions at 3 years was higher in the LP group than the LR group (9.9% vs. 2.2%, p = 0.040). ConclusionsLR of nonculprit subclinical atherosclerosis at 1-year follow-up was mainly caused by regression of the lipid component, which was correlated with the degree of LDL-C reduction and fewer MACEs at 3-year follow-up.

Quantitative plaque analysis with A.I.-augmented CCTA in end-stage renal disease and complex CAD

BackgroundAdverse cardiovascular events are a significant cause of mortality in end-stage renal disease (ESRD) patients. High-risk plaque anatomy may be a significant contributor. However, their atherosclerotic phenotypes have not been described. We sought to define atherosclerotic plaque characteristics (APC) in dialysis patients using artificial-intelligence augmented CCTA. MethodsWe retrospectively analyzed ESRD patients referred for CCTA using an FDA approved artificial-intelligence augmented-CCTA program (Cleerly). Coronary lesions were evaluated for APCs by CCTA. APCs included percent atheroma volume(PAV), low-density non-calcified-plaque (LD-NCP), non-calcified-plaque (NCP), calcified-plaque (CP), length, and high-risk-plaque (HRP), defined by LD-NCP and positive arterial remodeling >1.10 (PR). Results79 ESRD patients were enrolled, mean age 65.3 years, 32.9% female. Disease distribution was non-obstructive (65.8%), 1-vessel disease (21.5%), 2-vessel disease (7.6%), and 3-vessel disease (5.1%). Mean total plaque volume (TPV) was 810.0 mm3, LD-NCP 16.8 mm3, NCP 403.1 mm3, and CP 390.1 mm3. HRP was present in 81.0% patients. Patients with at least one >50% stenosis, or obstructive lesions, had significantly higher TPV, LD-NCP, NCP, and CP. Patients >65 years had more CP and higher PAV. ConclusionOur study provides novel insight into ESRD plaque phenotypes and demonstrates that artificial-intelligence augmented CCTA analysis is feasible for CAD characterization despite severe calcification. We demonstrate elevated plaque burden and stenosis caused by predominantly non-calcified-plaque. Furthermore, the quantity of calcified-plaques increased with age, with men exhibiting increased number of 2-feature plaques and higher plaque volumes. Artificial-intelligence augmented CCTA analysis of APCs may be a promising metric for cardiac risk stratification and warrants further prospective investigation.

Detailed behaviour of endothelial wall shear stress across coronary lesions from non-invasive imaging with coronary computed tomography angiography.

Evolving evidence suggests that endothelial wall shear stress (ESS) plays a crucial role in the rupture and progression of coronary plaques by triggering biological signalling pathways. We aimed to investigate the patterns of ESS across coronary lesions from non-invasive imaging with coronary computed tomography angiography (CCTA), and to define plaque-associated ESS values in patients with coronary artery disease (CAD). Symptomatic patients with CAD who underwent a clinically indicated CCTA scan were identified. Separate core laboratories performed blinded analysis of CCTA for anatomical and ESS features of coronary atherosclerosis. ESS was assessed using dedicated software, providing minimal and maximal ESS values for each 3 mm segment. Each coronary lesion was divided into upstream, start, minimal luminal area (MLA), end and downstream segments. Also, ESS ratios were calculated using the upstream segment as a reference. From 122 patients (mean age 64 ± 7 years, 57% men), a total of 237 lesions were analyzed. Minimal and maximal ESS values varied across the lesions with the highest values at the MLA segment [minimal ESS 3.97 Pa (IQR 1.93-8.92 Pa) and maximal ESS 5.64 Pa (IQR 3.13-11.21 Pa), respectively]. Furthermore, minimal and maximal ESS values were positively associated with stenosis severity (P < 0.001), percent atheroma volume (P < 0.001), and lesion length (P ≤ 0.023) at the MLA segment. Using ESS ratios, similar associations were observed for stenosis severity and lesion length. Detailed behaviour of ESS across coronary lesions can be derived from routine non-invasive CCTA imaging. This may further improve risk stratification.

Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction

Coronary plaques that are prone to rupture and cause adverse cardiac events are characterized by large plaque burden, large lipid content, and thin fibrous caps. Statins can halt the progression of coronary atherosclerosis; however, the effect of the proprotein convertase subtilisin kexin type 9 inhibitor alirocumab added to statin therapy on plaque burden and composition remains largely unknown. To determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction. The PACMAN-AMI double-blind, placebo-controlled, randomized clinical trial (enrollment: May 9, 2017, through October 7, 2020; final follow-up: October 13, 2021) enrolled 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction at 9 academic European hospitals. Patients were randomized to receive biweekly subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152), initiated less than 24 hours after urgent percutaneous coronary intervention of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy (rosuvastatin, 20 mg). Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and optical coherence tomography were serially performed in the 2 non-infarct-related coronary arteries at baseline and after 52 weeks. The primary efficacy end point was the change in IVUS-derived percent atheroma volume from baseline to week 52. Two powered secondary end points were changes in near-infrared spectroscopy-derived maximum lipid core burden index within 4 mm (higher values indicating greater lipid content) and optical coherence tomography-derived minimal fibrous cap thickness (smaller values indicating thin-capped, vulnerable plaques) from baseline to week 52. Among 300 randomized patients (mean [SD] age, 58.5 [9.7] years; 56 [18.7%] women; mean [SD] low-density lipoprotein cholesterol level, 152.4 [33.8] mg/dL), 265 (88.3%) underwent serial IVUS imaging in 537 arteries. At 52 weeks, mean change in percent atheroma volume was -2.13% with alirocumab vs -0.92% with placebo (difference, -1.21% [95% CI, -1.78% to -0.65%], P < .001). Mean change in maximum lipid core burden index within 4 mm was -79.42 with alirocumab vs -37.60 with placebo (difference, -41.24 [95% CI, -70.71 to -11.77]; P = .006). Mean change in minimal fibrous cap thickness was 62.67 μm with alirocumab vs 33.19 μm with placebo (difference, 29.65 μm [95% CI, 11.75-47.55]; P = .001). Adverse events occurred in 70.7% of patients treated with alirocumab vs 72.8% of patients receiving placebo. Among patients with acute myocardial infarction, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy resulted in significantly greater coronary plaque regression in non-infarct-related arteries after 52 weeks. Further research is needed to understand whether alirocumab improves clinical outcomes in this population. ClinicalTrials.gov Identifier: NCT03067844.

Multicenter Evaluation of Volumetric Intravascular Ultrasound Early After Heart Transplantation and Long-Term Prognosis

<h3>Purpose</h3> Previous studies found an increase in maximal intimal thickness (MIT) ≥0.5 mm during the first year after heart transplantation (HTx), based on 3-7 select cross-sectional intravascular ultasound (IVUS) images, predicts outcome. Consensus recommendations advise against select image analysis and long vessel (40-50 mm) volumetric evaluation is preferred. However, the prognostic utility of such assessment in HTx is unclear. This study determined the relationship between long vessel volumetric IVUS evaluation early after HTx and long-term outcome. <h3>Methods</h3> HTx recipients from four institutions underwent IVUS at 12 weeks and one year post-HTx and long vessel volumetric IVUS evaluation was performed. All-cause mortality was the primary and major adverse cardiac events (MACE i.e. composite of cardiac death, re-HTx, myocardial infarction, heart failure or coronary revascularization) was the secondary endpoint. <h3>Results</h3> Of 243 HTx recipients (mean follow-up 8.1±3.1 years) those with Percent Atheroma Volume (PAV) increase ≥7.0% (absolute percentage units) had a significantly increased risk of all-cause mortality (34% vs 14%, p=0.01; adjusted hazard ratio (HR) 2.60 (95% CI 1.37-4.93, p<0.01)) and MACE (40% vs 21%, p=0.04; adjusted HR 1.99 (95% 1.15-3.45, p=0.01)). MIT increase ≥0.5 mm was not associated with increased risk of all-cause mortality or MACE. <h3>Conclusion</h3> With long-vessel IVUS analysis, PAV increase≥7.0% (absolute percentage units) during the first year post-HTx predicts subsequent all-cause mortality and MACE, whereas the previously established threshold of MIT increase ≥0.5 mm does not.

Coronary CTA plaque volume severity stages according to invasive coronary angiography and FFR

BackgroundAtherosclerotic plaque characterization by coronary computed tomography angiography (CCTA) enables quantification of coronary artery disease (CAD) burden and type, which has been demonstrated as the strongest discriminant of future risk of major adverse cardiac events (MACE). To date, there are no clinically useful thresholds to assist with understanding a patient's disease burden and guide diagnosis and management, as there exists with coronary artery calcium (CAC) scoring. The purpose of this manuscript is to establish clinically relevant plaque stages and thresholds based on evidence from invasive angiographic stenosis (ICA) and fractional flow reserve (FFR) data. Methods303 patients underwent CCTA prior to ICA and FFR for an AHA/ACC clinical indication. Quantitative computed tomography (QCT) was performed for total plaque volume (TPV, mm3) and percent atheroma volume (PAV, %). We segmented atherosclerosis by composition for low-density non-calcified plaque (LD-NCP), non-calcified plaque (NCP), and calcified plaque (CP). ICAs were evaluated by quantitative coronary angiography (QCA) for all coronary segments for % diameter stenosis. The relationship of atherosclerotic plaque burden and composition by QCT to ICA stenosis extent and severity by QCA and presence of ischemia by FFR was assessed to develop 4 distinct disease stages. ResultsThe mean age of the patients was 64.4 ​± ​10.2 years; 71% male. At the 50% QCA stenosis threshold, QCT revealed a mean PAV of 9.7 (±8.2)% and TPV of 436 (±444.9)mm3 for those with non-obstructive CAD; PAV of 11.7 (±8.0)% and TPV of 549.3 (±408.3) mm3 for 1 vessel disease (1VD), PAV of 17.8 (±9.8)% and TPV of 838.9 (±550.7) mm3 for 2VD, and PAV of 19.2 (±8.2)% and TPV of 799.9 (±357.4) mm3 for 3VD/left main disease (LMD). Non-ischemic patients (FFR >0.8) had a mean PAV of 9.2 (±7.3) % and TPV of 422.9 (±387.9 ​mm3) while patients with at least one vessel ischemia (FFR ≤0.8) had a PAV of 15.2 (±9.5)% and TPV of 694.6 (±485.1). Definition of plaque stage thresholds of 0, 250, 750 ​mm3 and 0, 5, and 15% PAV resulted in 4 clinically distinct stages in which patients with no, nonobstructive, single VD and multi-vessel disease were optimally distributed. ConclusionAtherosclerotic plaque burden by QCT is related to stenosis severity and extent as well as ischemia. We propose staging of CAD atherosclerotic plaque burden using the following definitions: Stage 0 (Normal, 0% PAV, 0 ​mm3 TPV), Stage 1 (Mild, >0–5% PAV or >0–250 ​mm3 TPV), Stage 2 (Moderate, >5–15% PAV or >250–750 ​mm3 TPV) and Stage 3 (Severe, >15% PAV or >750 mm3 TPV).

Effect of Evolocumab on Coronary Plaque Phenotype and Burden in Statin-Treated Patients Following Myocardial Infarction

BackgroundThe proprotein convertase subtilisin kexin type-9 inhibitor evolocumab produced coronary atheroma regression in statin-treated patients. ObjectivesThe purpose of this study was to determine the effect of evolocumab on optical coherence tomography (OCT) measures of plaque composition. MethodsPatients with a non–ST-segment elevation myocardial infarction were treated with monthly evolocumab 420 mg (n = 80) or placebo (n = 81) for 52 weeks. Patients underwent serial OCT and intravascular ultrasound imaging within a matched arterial segment of a nonculprit vessel. The primary analysis determined the change in the minimum fibrous cap thickness and maximum lipid arc throughout the imaged arterial segment. Additional analyses determined changes in OCT features in lipid-rich plaque regions and plaque burden. Safety and tolerability were evaluated. ResultsAmong treated patients (age 60.5 ± 9.6 years; 28.6% women; low-density lipoprotein cholesterol [LDL-C], 141.3 ± 33.1 mg/dL), 135 had evaluable imaging at follow-up. The evolocumab group achieved lower LDL-C levels (28.1 vs 87.2 mg/dL; P < 0.001). The evolocumab group demonstrated a greater increase in minimum fibrous cap thickness (+42.7 vs +21.5 μm; P = 0.015) and decrease in maximum lipid arc (−57.5o vs. −31.4o; P = 0.04) and macrophage index (−3.17 vs −1.45 mm; P = 0.04) throughout the arterial segment. Similar benefits of evolocumab were observed in lipid-rich plaque regions. Greater regression of percent atheroma volume was observed with evolocumab compared with placebo (−2.29% ± 0.47% vs −0.61% ± 0.46%; P = 0.009). The groups did not differ regarding changes in microchannels or calcium. ConclusionsThe combination of statin and evolocumab after a non–ST-segment elevation myocardial infarction produces favorable changes in coronary atherosclerosis consistent with stabilization and regression. This demonstrates a potential mechanism for the improved clinical outcomes observed achieving very low LDL-C levels following an acute coronary syndrome. (Imaging of Coronary Plaques in Participants Treated With Evolocumab; NCT03570697)