Non-calcified Plaque Research Articles

Abstract 4144554: Revascularization of Patients with Low-Density Non-Calcified Plaque was Associated with Lower Occurrence of Acute Coronary Syndrome

INTRODUCTION: Coronary CT angiography (CCTA) is a powerful noninvasive tool for identifying high-risk plaque, such as low-density non-calcified plaque (LD-NCP). Though, the optimal treatment of patients with LD-NCP remains unclear. This study explored the association of revascularization in the setting of LD-NCP with the occurrence of acute coronary syndrome (ACS). Methods: This was a post-hoc analysis of the ICONIC study. A subset of 234 patients that underwent CCTA with subsequent ACS were matched to 234 control patients who also underwent CCTA but did not have ACS during follow-up. Patients were also followed for occurrence of revascularization, either coronary artery bypass graft or percutaneous coronary intervention. Atherosclerosis imaging-enabled quantitative CT (AI-QCT) was used to measure diameter stenosis, and LD-NCP, non-calcified plaque, and calcified plaque volumes from each CCTA. LD-NCP was defined as plaque with -190 to 30 Hounsfield Units. Patients were stratified based on the presence of LD-NCP. Subgroup analysis was conducted to compare the occurrence of ACS with the rate of revascularization. Kaplan-Meier survival curves and extended Cox regression analysis were used to evaluate the effect size of revascularization and LD-NCP on occurrence of ACS. Results: AI-QCT was completed in 448/468 subjects (follow-up time [MEAN±SD] 2.44±2.48 years). The median of LD-NCP was 1.2 mm 3 for patients with >0 mm 3 LD-NCP. There were 85 patients with LD-NCP >1.2 mm 3 and 363 patients with LD-NCP ≤1.2 mm 3 . In patients with LD-NCP >1.2 mm 3 , the rate of revascularization in patients with and without ACS was 3/52 (5.8%) versus 14/33 (42.4%) (p<0.001). In patients with LD-NCP ≤1.2 mm 3 , the rate of revascularization in patients with and without ACS was 36/170 (21.2%) versus 39/193 (20.2%) (p=0.897). In comparison to patients without revascularization and LD-NCP ≤1.2 mm 3 , patients with LD-NCP >1.2 mm 3 and revascularization were less likely to have ACS during follow-up (adjusted HR: 0.20 [0.07, 0.61]; p=0.005). Additionally, patients with LD-NCP >1.2 mm 3 who did not undergo revascularization were more likely to have ACS (adjusted HR: 1.47 [1.03, 2.12]; p=0.036). Hazard ratios were adjusted for diameter stenosis, and non-calcified and calcified plaque volume. Time-dependent coefficients were included for diameter stenosis. Conclusion: Revascularization of patients with LD-NCP >1.2 mm 3 identified on CCTA with AI-QCT was associated with less risk for ACS.

Abstract 4135636: Age- and Sex-Related Coronary Atherosclerosis by Artificial Intelligence Quantitative Coronary CT Angiography from the INVICTUS Registry

Background: Coronary plaque analysis using artificial intelligence quantitative coronary CT (AI-QCT) is a promising tool to identify coronary atherosclerosis. However, there is insufficient data on coronary atherosclerosis volume and morphology using AI-QCT in patients who are at high risk of atherosclerosis. The purpose of this study is to clarify the differences in the volume and phenotypes of coronary atherosclerosis by age and gender using AI-QCT. Methods: The INVICTUS Registry is a multi-center registry enrolling patients who clinically underwent coronary CT angiography and invasive coronary angiography with invasive imaging modalities in Japan. Patients with a history of percutaneous coronary intervention or coronary artery bypass graft were excluded in this study. Using AI-QCT, the volume, and phenotypes (calcified, non-calcified, low-density non-calcified plaque [LD-NCP]) of coronary atherosclerosis were analyzed and assessed by age (<55, 55-64, 65-74, and 75 and older) and gender. Results: A total of 982 patients were enrolled in the study. The mean age was 70.3 ± 10.8 years, 71.9% were male. Approximately two-thirds of patients had hypertension (73.3%) and dyslipidemia (71.5%), and 36.7% had diabetes. Mean total plaque volume (PV), calcified PV, non-calcified PV, and low-density PV were 745.5±529.8 mm 3 , 248.3±302.0 mm 3 , 482.2±340.6 mm 3 , and 15.0±29.4 mm 3 , respectively. The results of plaque volume and phenotypes by age are shown in the figure. Compared to those under 55 years of age, total PV increased gradually and significantly by about 10% for every 10 years of age (p=0.022). Though no significant difference was observed in non-calcified PV between the age groups (p=0.379), calcified PV progressively and significantly increases approximately 70% for every 10 years of age (p<0.001). In contrast, the low-density plaque volume showed a trend toward a significant decrease with increasing age (p=0.073). These trends did not differ by gender. Conclusion: In a large cohort of patients at high risk for atherosclerosis analyzed by AI-QCT, total coronary PV increased with age, primarily calcified PV. While no change in non-calcified PV between the age groups, LD-NCPV was likely to decrease with increasing age. These findings may contribute to the guidance for the prevention of coronary artery diseases based on coronary atherosclerosis phenotype by age and gender.

Abstract 4120670: Pericoronary Adipose Tissue Inflammation as a Marker of Increased Coronary Plaque Burden in Patients With Chronic Coronary Artery Disease With Zero Calcium Score

Background: Dysfunctional or excess adiposity plays pivotal role in the development of coronary atherosclerosis. It remains unclear whether pericoroanry adipose tissue (PCAT) inflammation is associated with increased coronary plaque burden in its early stage of atherosclerosis, independent of traditional coronary risks or cardiovascular-kidney metabolic health. Purpose: To investigate the association of PCAT inflammation with coronary plaque burden in patients with newly suspected with chronic coronary artery disease (CAD) and zero calcium score who underwent coronary computed tomography angiography (CCTA). Methods: This retrospective CCTA study consists of 294 chronic CAD patients with zero calcium score (59 years, male 51 %). Chronic CAD was defined as stable condition with presence of increased non-calcified plaque burden on CCTA (Figure 1A-D). PCAT attenuation (PCATA) was assessed by fat attenuation index in the major three coronary arteries (right coronary artery, RCA; left anterior descending artery; LAD, and left circumflex coronary artery, LCX)(Figure 1C and D). Multivariable analysis using linear regression model was performed to determine independent predictors of increased %PV by adjusting for traditional coronary risks, metabolic risks, and chronic kidney disease (CKD). Hisayama Risk Score (HRS) was calculated to estimate 10-year cardiovascular risks. Results: Mean %plaque volume (PV) and PCATA-RCA was 44±4.0％ and -77±8.8 HU. %PV was correlated with age (p<0.05), systolic blood pressure (p<0.05), non-HDL cholesterol (p<0.05), Hisayama risk score (p<0.05, Figure 2), PCATA-RCA (p<0.001, Figure 3), PCATA-LAD (p<0.001), and LCX-PCATA (p<0.001). In a multivariable linear regression model adjusting for age, sex, hypertension, diabetes, dyslipidemia, and current smoking (model 1), PCATA-RCA was independently associated with %PV [beta, 0.17; 95% confidential interval (CI) 0.115-0.217, p < 0.001]. In a model adjusting for age, sex, metabolic syndrome, body mass index ≥23kg/mm 2 , and CKD (model 2), PCATA-RCA (beta, 0.18; 95% CI 0.128-0.232, p<0.001) and high-risk HRS (beta, 3.1; 95% CI 1.35−4.87, p<0.001) were independently associated with %PV. Similarly, independent associations of PCATA in LAD and LCX with %PV was observed. Conclusion: This study demonstrates that PCATA is a robust marker related to increased burden of coronary atherosclerosis even in the early stage of atherosclerosis as defined by zero coronary artery calcium score.

Abstract 4131815: The Prevalence of Normal Coronary Arteries as Determined by a Coronary Artery Calcium Score of Zero Amongst Subjects with Diabetes Mellitus

Background: The CDC reports that in 2021, 11.6% of the American population had diabetes mellitus (DM). Past literature has shown diabetes to be a significant risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). Research Question/Goal: Using data obtained through Computed Tomography Angiography (CTA), we aim to distinguish the risk factors associated with a coronary artery calcium (CAC) score of zero in subjects with DM and to identify the prevalence of non-calcified plaque in individuals with this score. Methods: We performed a retrospective study of patients with DM, who underwent CAC and CTA screenings from October 2004 to January 2024 at our center in Torrance, California to examine CTA outcomes in those with CAC Score of zero and greater than zero. Results: Among the cohort of 2,763 subjects with DM, the average age was 63.8±12.2 years, 62% male. Within this cohort, 465 (17%) subjects had a CAC Score of zero compared to 2,298 subjects with a CAC Score greater than zero with a median score of 428 (Interquartile range (IQR) 91-1267). DM subjects with CAC Score of zero were significantly younger (53.0±13.9 versus 66.0±10.6: p<0.001), were more likely to be female and had significantly lower rates of hypertension (57% versus 76%: p<0.001), and hyperlipidemia (63% versus 76%: p<0.001). In DM subjects with CAC Score of zero, 133 (29%) had a total plaque severity score of 1 or greater (median 1, IQR 1-2) while 332 (71%) had normal coronaries on CTA. Conclusions: A significant percentage of subjects with DM were determined to have a CAC score of zero. Subjects with normal coronary arteries were more likely to be younger, female, and/or absent of other chronic diseases such as hypertension and hyperlipidemia. Although age and sex are nonmodifiable risk factors of ASCVD, limiting the comorbid conditions associated with DM may be beneficial in preventing ASCVD in individuals with diabetes.

Characterizing Nonculprit Lesions and Perivascular Adipose Tissue of Patients Following Acute Myocardial Infarction Using Coronary Computed Tomography Angiography: A Comparative Study.

The comparison of coronary computed tomography angiography plaques and perivascular adipose tissue (PVAT) between patients with acute myocardial infarction (AMI) posttreatment and patients with stable coronary artery disease is poorly understood. Our objective was to evaluate the differences in coronary computed tomography angiography-quantified plaque and PVAT characteristics in patients post-AMI and identify signs of residual inflammation. We analyzed 205 patients (age, 59.77±9.24 years; 92.20% men) with AMI ≤1 month and matched them with 205 patients with stable coronary artery disease (age, 60.52±10.04 years; 90.24% men) based on age, sex, and cardiovascular risk factors. Coronary computed tomography angiography scans were assessed for nonculprit plaque and vessel characteristics, plaque volumes by composition, high-risk plaques, and PVAT mean attenuation. Both patient groups exhibited similar noncalcified plaque volumes (383.35±313.23 versus 378.63±426.25 mm3, P=0.899). However, multivariable analysis revealed that patients post-AMI had a greater patient-wise noncalcified plaque volume ratio (estimate, 0.089 [95% CI, 0.053-0.125], P<0.001), largely attributed to a higher fibrofatty and necrotic core volume ratio, along with higher peri-lesion PVAT mean attenuation (estimate, 3.968 [95% CI, 2.556-5.379], P<0.001). When adjusted for vessel length, patients post-AMI had more high-risk plaques (estimate, 0.417 [95% CI, 0.298-0.536], P<0.001) per patient. Patients post-AMI displayed heightened noncalcified plaque components, largely due to fibrofatty and necrotic core content, more high-risk plaques, and increased PVAT mean attenuation on a per-patient level, highlighting the necessity for refined risk assessment in patients with AMI after treatment.

Reduced inflammation assessed by pericoronary adipose tissue is associated with coronary plaque calcification

Abstract Introduction Pericoronary adipose tissue attenuation (PCAT) quantified from coronary computed tomography angiography (CCTA) is increasingly recognized as an inflammation marker in coronary artery disease (CAD). Inflamed PCAT has been linked to non-calcified plaque (NCP) and cardiovascular morbidity and mortality. Nevertheless, gaps remain in understanding how PCAT behaves during plaque stabilization. Purpose We investigated associations between coronary artery inflammation assessed by PCAT and the presence and type of coronary plaques, plaque burden, and coronary calcification. Methods An observational study involving 506 patients with suspected chronic coronary syndrome who underwent CCTA. PCAT was averaged across the proximal 40 mm segments of all three coronary vessels to represent the patient level. Plaque presence and types (calcified, mixed, and soft) were assessed. Total, NCP, and calcified plaque (CP) burdens were measured as normalized atheroma volumes. Coronary calcification was quantified using Agatson coronary artery calcification (CAC) score and categorized based on cut-offs of 0, 100, 400. Results The mean PCAT was -81.1 ±6.3 Hounsfield Unit (HU) without plaque and -79.7 ±6.0 HU with plaque (p= 0.01). PCAT differed between calcified (-81.8 HU), mixed (-79.8 HU), and soft (-77.0 HU) plaques (p&amp;lt;0.0001). Multivariate linear analysis (adjusted for clinical risk factors, cardiovascular medication, and tube voltage) showed PCAT positively associated with total plaque burden (estimate= 1.1 [95% CI: 0.3-1.8], p=0.004) and NCP burden (estimate= 2.4 [95% CI: 1.4-3.4]; p&amp;lt;0.0001), while the association with CP burden was negative, but not statistically significant (estimate= -1.7 [95%CI : -4.1-0.7], p=0.2). Multivariate linear analysis, which accounted for both calcified and non-calcified plaque, reaffirmed the positive association to NCP burden (estimate= 2.7 [95% CI: 1.7-3.7]; p&amp;lt;0.0001) and a significant negative association between CP burden (estimate= - 3.3 [95% CI: -5.8- -1.0]; p=0.007) and PCAT. No significant differences in PCAT levels were found among patients with a CAC score of 0 and those with CAC scores exceeding 400, or across different stages of CAC score categories (p&amp;gt;0.8). Conclusion PCAT increased with plaque presence, rising from calcified to mixed to soft plaques. Increased NCP burden associated with higher PCAT, while higher CP burden seemed to reduce PCAT, though not statistical significant. Interestingly, when NCP was absent, higher levels of CP burden were associated with reduced inflammation. This supports the hypothesis of plaque stabilization, proposing that calcification might stabilize the vessel and indirectly contribute to reducing inflammation.Figure 1 PCAT by plaque typesTable 1 PCAT &amp; plaque burden

Association of sodium-glucose cotransporter-2 inhibitor with regression of coronary plaque burden

Abstract Background Sodium-glucose cotransporter-2 inhibitor (SGLT2i), as a novel oral hypoglycemic therapy of type 2 diabetes mellitus (T2DM), has been proved to benefit cardiac function. However, it remains unknown whether SGLT2i has an impact on coronary plaque characteristics. Purpose The aim of this study was to investigate whether SGLT2i was able to improve coronary plaque composition, burden and inflammation [i.e., fat attenuation index (FAI)] using series coronary computed tomography angiography (CCTA) images among T2DM patients with angina pectoris. Methods T2DM patients presenting with angina pectoris admitted at our center were screened. Eligible patients were those underwent first CCTA within 3 months prior to initiating SGLT2i therapy, and repeated CCTA beyond 6 months after the first CCTA. Those patients not treated with SGLT2i underwent likewise longitudinal CCTA tests were propensity score matching in a 1:1 ratio using age, sex and CCTA time interval. Routine CCTA images were assessed for coronary plaque characteristics using dedicated softwares. Paired or unpaired Student’s t test or Mann–Whitney U test were used for comparing coronary plaque characteristics between series CCTA and patients with or without SGLT2i. The relationships between SGLT2i and changes of plaque characteristics was examined using logistic regression analysis. Results After propensity score matching, a total of 196 T2DM patients with angina pectoris were included (mean age, 60.4±9.2 years; male, 69.9%; SGLT2i treatment, 50%). Time interval between baseline and the last CCTA examinations was 400 (343,496) days. In the SGLT2i group, the non-calcified plaque burden [(39.86±14.30)% vs. (36.84±13.86)%, p=0.002)] and low attenuation non-calcified plaque burden (6.62 [4.11,10.13]% vs. 5.78 [3.40,9.28]%, p=0.042) were significantly decreased between two CCTA images. Whereas, in the non-SGLT2i group, there was no difference with regard to non-calcified and low attenuation non-calcified plaque burden between two CCTA images (all p&amp;gt;0.05). Moreover, changes of total plaque burden and non-calcified plaque burden were higher in the SGLT2i group than the non-SGLT2i group (all p&amp;lt;0.05). Importantly, SGLT2i was associated with total plaque volume (odd ratio=0.594, p=0.024) and non-calcified plaque volume regression (odd ratio=0.619, p=0.042) after adjusting for confounding factors. Conclusion SGLT2i significantly regresses coronary plaque burden, in particularly non-calcified plaque. These findings might explain the observed cardio-protective effect of SGLT2i in large trials.

Low density lipoprotein cholesterol and cardiovascular disease risk in patients with absence of coronary artery calcification: a multicenter cohort study

Abstract Background Low-density lipoprotein cholesterol (LDL-C) plays a central role in the development of coronary heart disease (CHD). Absence of coronary artery calcification (CAC 0), as assessed by coronary computed tomography angiography (CCTA), is associated with a favorable outcome as it indicates a low burden of atherosclerosis. However, questions remain regarding the risk of non-calcified plaque and CHD in younger patients with CAC zero, as atherosclerosis tends to be non-calcified in earlier stages. Purpose To assess if LDL-C is associated with presence of non-calcified plaque and future cardiovascular events in patients with CAC zero across the age spectrum. Methods This observational multicenter cohort study included patients aged 18 years or more who underwent CCTA between January 2008 and May 2021 with CAC zero. LDL-C was measured prior to CCTA. Patients were followed from date of CCTA to occurrence of cardiovascular event, death, or 1st of October 2022. No patients were lost to follow-up. We assessed the association between LDL-C and presence of non-calcified plaque on CCTA as adjusted odds ratios, and risk for myocardial infarction and CHD (myocardial infarction or coronary revascularization) as adjusted hazard ratios using Cox regression analyses, across different age groups. Results A total of 23,776 patients with CAC zero were included in the study. Median age was 54 years (IQR 47-61) and 14,605 (61%) were women. During median follow-up of 5.5 years, 165 (0.7%) and 427 (1.8%) experienced myocardial infarction and CHD, respectively. Overall, the prevalence of non-calcified plaque was 11.1% (n=2,650). Higher LDL-C was associated with presence of non-calcified plaque with an odds ratio of 1.21 (95% CI 1.16-1.27) per 1 mmol/L higher LDL-C. Individuals aged ≤45 years had a higher odds ratio for non-calcified plaque per 1 mmol/L higher LDL-C compared to individuals aged 46-60 and &amp;gt;60 years; 1.36 (95% CI 1.22-1.52), 1.22 (95% CI 1.15-1.30) and 1.13 (95% CI 1.04-1.22), respectively, p value for interaction between the youngest and oldest age group was &amp;lt;0.05. Overall, LDL-C was associated with higher risk for myocardial infarction and CHD with hazard ratios of 1.29 (95% CI 1.10-1.52) and 1.26 (95% CI 1.14-1.39) per 1 mmol/L higher LDL-C, despite CAC zero. Conclusions Particularly in younger patients with absence of CAC, elevated LDL-C is associated with presence of non-calcified plaque and increased risk for future cardiovascular events. These data are important for clinical practice, as they demonstrate the importance of managing LDL-C in younger individuals over the long-time horizon despite CAC zero.

Coronary CT angiography using photon counting CT for the detection of coronary artery stenoses and coronary atherosclerotic plaque: comparison of reconstructions with 0.2 mm and 0.4 mm slice thickness

Abstract Photon Counting CT allows the acquisition of high-resolution data sets with 0.2 mm reconstructed slice thickness. It is unknown whether the detection of coronary artery stenoses, of coronary plaque or of vulnerable plaque characteristics is improved in data sets that employ maximum resolution. We therefore compared the identification of above characteristics in data sets reconstructed with 0.2 mm and 0.4 mm slice thickness In 30 patients with suspected coronary artery disease, sinus rhythm, a heart rate ≤65 beats/min, and body weight ≤ 100 kg, high-resolution data sets were acquired by photon counting CT (60 ml contrast i.v. at 6 ml/s) after s.c. application of nitrates in inspiratory breathhold. Data were reconstructed with 0.2 mm slice thickness at 0.1 mm increment and 0.4 mm slice thickness at 0.2 mm increment. Next to quantitative analysis of image quality parameters, all data sets were evaluated by two independent expert reviewers concerning subjective image quality as well as the ability to determine the presence of coronary artery stenoses, calcified and non- calcified plaque, as well as parameters of plaque vulnerability (positive remodeling, necrotic core, density &amp;lt; 30 HU and napkin-ring sign) using a 5-point Likert scale (-2 to +2) and a dedicated 11-segment coronary model. Of the 30 patients, 47% were male (mean age 58±12 years, mean heart rate 53±6 bpm, mean body weight 80±15 kg). The median dose length product was 508 mGy*cm. Mean image noise was 42±7 HU vs. 34±7 HU for 0.2 mm vs. 0.4 mm reconstructions (p &amp;lt; 0.001). The median image quality score was significantly higher for 0.2 mm reconstructions (3.8±0.8 vs 3.6±0.7). Of 335 coronary segments, none were classified as "unevaluable" while 87% vs. 76% were classified as "perfect" in 0.2 mm vs. 0.4 mm reconstructions (p &amp;lt; 0.001). Full confidence to rule-in or rule out significant coronary stenoses was achieved in 93% of segments in both reconstructions. The number of non-calcified plaques identified in 0.2 mm reconstructions was numerically higher than in 0.4 mm reconstructions (77 vs. 71, p = n.s.). On the Likert scale, the confidence to identify parameters of plaque vulnerability was significantly higher for 0.2 mm reconstructions (1.93 vs. 1.85, p &amp;lt; 0.001). In a selected patient group, photon counting CT coronary angiography demonstrated excellent image quality and an extremely low rate of unevaluable coronary segments. High-resolution reconstructions improve subjective image quality as was as the assessment of vulnerable plaque characteristics.

Predictors of percutaneous coronary intervention derived from CCTA in patients with chronic coronary syndrome

Abstract Background To identify anatomical and morphological plaque features predictors of percutaneous coronary intervention (PCI) and create a multiparametric score to increase the predictive yield. Moreover, we assessed the incremental predictive value of FFRCT (Fractional Flow Reserve derived from CCTA) trans-lesion gradient (ΔFFRCT) when integrated into the score. Methods Observational cohort study including patients undergoing CCTA for suspected coronary artery disease, with FFRCT available, referred to invasive coronary angiogram and assessment of fractional flow reserve. Plaque analysis was performed using validated semi-automated software. Logistic regression was performed to identify anatomical and morphological plaque features predictive of PCI. Optimal thresholds were defined by area under the receiver-operating characteristics curve (AUC) analysis. A scoring system was developed in a derivation cohort (70% of the study population) and tested in a validation cohort (30% of patients). Results The overall study population included 340 patients (455 vessels), among which 238 patients (320 vessels) were included in the derivation cohort. At multivariate logistic regression analysis, absence of left main disease, diameter stenosis (DS), non-calcified plaque (NCP) volume, and percent atheroma volume (PAV) were independent predictors of PCI. Optimal thresholds were: DS³50%, volume of NCP&amp;gt;113 mm3 and PAV&amp;gt;17%. A weighted score (CT-PCI Score) ranging from 0 to 11 was obtained. The AUC of the score was 0.80 (95%CI 0.74-0.86). The integration of ΔFFRCT in the CT-PCI score led to a mild albeit not significant increase in the AUC (0.82, 95%CI 0.77-0.87, p=0.328). Conclusions Plaque anatomy and morphology derived from CCTA could aid in identifying patients amenable to PCI.Central IllustrationPredictive accuracy of the CT-PCI score

Interscan reproducibility of computed tomography derived coronary plaque volume measurements using a semi-automated analysis software

Abstract Background Coronary computed tomography angiography (CCTA) enables detailed quantification and characterization of coronary atherosclerotic plaque, offering diagnostic and prognostic value. Despite the growing demand for accurate plaque analysis, studies on interscan reproducibility of automated plaque quantification are limited in number and size. Moreover, impact of clinical and technical factors on the reproducibility of plaque assessment tools are scarce. Purpose The objective of this study was to assess the interscan reproducibility of CCTA-derived plaque volume measurements and the implications of clinical and technical characteristics on interscan reproducibility. Methods A total of 101 patients with known coronary artery disease underwent two CCTA scans within hour interval using identical CT acquisition protocol. Coronary plaque volume measurements were quantified on a per-patient level using a contemporary semi-automated plaque analysis software. Results There was no statistically significant difference in median plaque volumes between the first and second scan. The direct correlation was excellent for volumes of non-calcified plaque (NCP), calcified plaque (CP), and total plaque (TP) across all analyses (Pearson’s coefficient 0.96 to 0.99), while moderate for low-density non-calcified plaque (LD-NCP) volumes (Pearson’s coefficient 0.77). Bland Altman analyses demonstrated high interscan agreement with narrow absolute and relative limits of agreement (LoA) across plaque subtypes, except for LD-NCP volumes (Table 1). Interscan reproducibility on CP volumes was affected by CT image quality with narrower LoA in scans with the highest image quality score (p = 0.003), or lowest image reconstructive iteration level (p &amp;lt;0.001). Limits of agreement were significantly narrower for NCP, CP, and TP volumes in lesions located in LAD compared to non-LAD lesions (p &amp;lt;0.001). However, no significant difference in LoA was present when comparing patients according to BMI (&amp;lt;27 and ≥27 kg/m2), heart rate (&amp;lt;65 and ≥65 beats per minute), or Agatston score (&amp;lt;193 and ≥193). Conclusions This comprehensive interscan reproducibility study revealed good agreement in the measurement of plaque subtypes. Adding new insight to existing literature, we have demonstrated that factors such as image quality, image reconstructive algorithms, and lesion location affect the reproducibility of plaque volume measurements. CT-derived plaque quantification using a semi-automated plaque analysis software holds potential for monitoring disease progression or regression in patients with CAD, provided high CCTA image quality.

Correlation of coronary and carotid atheroma volume in patients with severe and familial hypercholesterolemia (VOCCA-3D HF)

Abstract Background Stratifying the risk of CV event of familial hypercholesterolemia (FH) patients is not always simple, as they usually are excluded from CV disease risk estimation scores. It has become increasingly clear over the last several years that the heterogeneity in risk among patients with FH is far greater than previously appreciated. To that end, not all patients with FH will require the use of PCSK9 inhibitors. Aim We described the type of coronary artery disease (CAD) in patients with severe and familial hypercholesterolemia and without known atherosclerotic cardiovascular disease and searched for the best determinants of CAD. We searched for correlation between epicardial adipose tissue and CAD. Methods We evaluated the atherosclerosis burden with a combination of calcium score (CAC), computed tomography angiography, and the quantification of coronary atheroma volume and the analysis of the composition of the plaques, alongside with the use of ultrasonography of supra-aortic trunks with 3D quantification of atheroma volume. We also evaluated epicardial adipose tissue volume with CT. Results We analyzed 89 individuals with LDL-c &amp;gt; 190 mg/dL, with a mean age of 56,7 years. LDL-c burden was high (maximal LDL-c level across life of 2.77 g/L in mean, duration of hypercholesterolemia of 21.5 years in mean). Forty percent of the individuals had a CAC score of zero, and only one patient had non-calcified atheroma despite a CAC score of zero. Among patients with CAD, 50% had a CAC &amp;gt; 100 AU, 9% had a stenosis &amp;gt; 50%. Coronary atheroma volume amounted to a median of 50.9 mm3 in patients with CAD, representing 4% of the analyzed coronary lumen volume, and was mainly made of calcified and non-calcified fibrous plaques. At-risk plaques were not frequent (9% of low-attenuation plaques, 15.2% of positive remodeling and 2% of napkin-ring sign) in patients with CAD. Fifty percent of the individuals had no carotid plaque. Among various clinical and biological risk factors (LDL-year-score, age, blood pressure, smoking, familial history, diabetes), the carotid atheroma volume was the only variable to be independently correlated with both CAC (t=3.1, p=0.006) and coronary atheroma volume (t=4.9, p&amp;lt;0.001). Epicardial adipose tissue was not associated with CAD. Conclusion A significant part of the patients with severe and familial hypercholesterolemia has no CAD, however half of the patients with CAD have an important atherosclerosis burden, which can be well predicted by the carotid atheroma volume. Such a screening could help identify the individuals who would benefit the most from intensive cholesterol-lowering drugs.CAC categoriesType of coronary plaques

Thrombus aspiration in people living with HIV- a night mare for interventionist

Abstract Background Cardiovascular disease, particularly atherosclerosis, and its complications are a growing cause of morbidity and mortality among individuals living with human immunodeficiency virus (HIV) in the post-antiretroviral therapy era. The role of thrombus aspiration combined with primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) within this population remains contentious. While PCI is the preferred strategy for immediate revascularization in acute STEMI, challenges persist, with about 30% of patients experiencing persistent chest pain and ST-segment elevation despite achieving TIMI III flow in the culprit vessel. Methods We conducted a prospective observational study spanning from January 2015 to September 2023, involving ten consecutive HIV-infected patients presenting with STEMI to our acute coronary care unit. The study encompassed an analysis of baseline clinical characteristics, response to fibrinolytic therapy, angiographic findings, thrombus aspiration using the Export Aspiration Catheter, and the outcomes of percutaneous coronary intervention (PCI). Patients were closely monitored for in-hospital outcomes and followed up for five years, during which they received adjuvant highly active antiretroviral therapy (HAART). Results The mean age of the patients was 46 years, lower than their uninfected counterparts. Most patients presented with a lower Killip class, indicating favorable outcomes. CD4 count distribution showed variability, with ten patients undergoing rescue angioplasty with thrombus aspiration using the Export Catheter. The cohort was followed for five years, receiving consistent HAART therapy. Conclusion HIV-associated atherosclerosis presents a considerable health burden, characterized by distinctive non-calcified and inflammatory plaques vulnerable to rupture. Thrombus aspiration during PCI emerged as a valuable strategy, reducing thrombotic burden and contributing to improved clinical outcomes in people living with HIV.

Computed tomography for prediction of stent underexpansion after percutaneous recanalization of calcified coronary chronic total occlusions

Abstract Background Coronary calcifications are the leading cause of stent underexpansion after percutaneous coronary intervention (PCI) and are commonly encountered in chronic total occlusions (CTO). Coronary computed tomography angiography (CCTA) is uniquely suited for pre-procedural assessment of coronary calcifications. Recently quantitative CCTA, providing exact volumes of each plaque component, has shown additional value in future risk assessment compared with conventional qualitative CCTA. Purpose The aim of this study was to evaluate whether CCTA predicts intravascular ultrasound (IVUS)-defined suboptimal stent expansion following percutaneous recanalization of calcified CTO lesions. Methods We retrospectively identified consecutive patients with a CCTA performed within 6-months prior to successful PCI of a calcified CTO (defined as calcification within the target lesion on CCTA). All patients had final IVUS of implanted stents (Figure 1). Patients requiring atherectomy were excluded. The primary outcome was IVUS-derived stent expansion index (SEI), defined as stent area divided by vessel area (both measured at the site of maximum calcium). SEI&amp;lt;0.4 indicated suboptimal stent expansion. The site of maximum calcium was a cross-section with greatest calcium arc on pre-stent IVUS within the target lesion. CCTA calcium analysis was performed by a researcher blinded to the IVUS and angiography results. Measurements included total-, vessel-, and lesion-specific calcium score (CAC), total calcium length, maximum calcium thickness and maximum CT calcium attenuation at the target lesion defined as occlusion site and adjacent severely diseased segments. Calcium quantification was performed using a semi-automated software to obtain volumes and burdens of calcified and non-calcified plaque components within the target lesion. Results The cohort included 43 patients (age 64.9±10.0 years, 88% males) with 43 CTO lesions. Mean final stent area at maximum calcium by IVUS was 8.2±2.1mm². Mean SEI was 0.47±0.1, and suboptimal SEI of &amp;lt;0.4 was found in 10 (23.3%) lesions. Lesions with suboptimal stent expansion (SEI&amp;lt;0.4) were characterized by numerically higher total-, vessel- and lesion-specific CAC, higher maximum calcium attenuation, greater calcium length and remodeling index compared with patients with optimal stent expansion (Table 1). However, only calcified plaque volume (105 [IQR 27-271] vs. 29 [4-96]mm³, P=0.02) and calcified plaque burden (16 [7-24] vs. 6 [1-10]%, P=0.03) were significantly greater in lesions with suboptimal stent expansion compared with lesions with optimal stent expansion, respectively. Calcified plaque volume ≥51 mm³ within the target lesion predicted suboptimal stent expansion with 70% sensitivity and 62.5% specificity (AUC 0.74). Conclusion CCTA-derived calcium volume identifies CTO lesions at greater risk of stent underexpansion. Such lesions require more aggressive plaque modification prior to stent implantation.

Efficacy of pitavastatin in patients with HIV: a systematic review and meta-analysis of randomized controlled trials

Abstract Background People with HIV (PWH) experience elevated cardiovascular disease (CVD) risk, exacerbated by antiretroviral therapy-induced dyslipidemia. Managing CVD risks in PWH presents significant challenges, notably due to the potential drug interactions. Pitavastatin is a statin with minimal interactions with antiretrovirals. Methods A systematic literature search of PubMed, Cochrane Library, and Embase databases was conducted up to March 1st, 2024, for studies comparing pitavastatin in PWH. Statistical software RStudio version 4.1.2 was used. Results Three studies with a total of 8045 participants were included in this analysis. Of these 4026 (50.04%) received pitavastatin. The mean age was 49.98 years and 69.38% were male. In the pooled analysis of studies, pitavastatin significantly reduced LDL cholesterol (MD -25.47; 95% CI -35.26 to -15.69; p&amp;lt;0.01; I² = 91%; Figure 1A) and non-HDL cholesterol (MD -27.53; 95% CI -41.19 to -13.87; p&amp;lt;0.01; I² = 91%; Figure 1B). Recently, the randomized trial to prevent vascular events in HIV study showed a reduction in adverse cardiovascular events and noncalcified plaque volume, as well as a reduction in inflammatory markers including oxidized LDL. Conclusions Pitavastatin offers a promising strategy for managing dyslipidemia and reducing CVD risk in PWH by reducing cholesterol, improving coronary plaque characteristics and inflammatory markers.

Artificial intelligence-based automated plaque quantification from CCTA to predict acute coronary syndrome on top of obstructive or ischemic coronary artery disease

Abstract Background Artificial intelligence (AI)-based quantitative computed tomography (AI-QCT) is a novel tool for automated plaque characterization and quantification from coronary computed tomography angiography (CCTA). The prognostic value of various AI-QCT plaque types on top of the presence of obstructive or ischemic coronary artery disease (CAD) is unknown. Purpose To investigate the added prognostic value for acute coronary syndrome (ACS) of AI-QCT total plaque burden (percent atheroma volume (PAV) %), and its subcomponents non-calcified plaque burden (NCPB), low-attenuation plaque burden (LAP), and calcified plaque burden (CPB) (%) on top of obstructive or ischemic CAD. Methods A cohort of 2007 symptomatic patients having undergone CCTA and selective downstream PET perfusion for suspected CAD was analyzed. Patients with prior or early elective revascularization within 6 months from CCTA were excluded. Obstructive CAD was defined as ≥1 vessel with &amp;gt;50% visual stenosis, and ischemic CAD as absolute hyperemic myocardial blood flow ≤2.3 ml/g/min in ≥2 adjacent segments on 15O-H2O PET. Multivariable Cox regressions adjusted for clinical confounders (age, sex hypertension, typical angina) including each plaque type separately (per 1.0%) on top of obstructive or ischemic CAD, respectively, were performed. The amount of LAP was &amp;lt;1% and therefore pooled together with NCPB. Results Throughout a median follow-up of 7 years, 72/2007 patients experienced ACS (50 myocardial infarction, 22 unstable angina). On top of obstructive CAD, all plaque types were independent predictors of ACS (Figure 1A), however according to the C-indexes (p-value vs. obstructive CAD), only PAV (C-index=0.814, p=0.010) and NCPB+LAP (C-index=0.818, p=0.014), but not CPB (C-index=0.800, p=0.066) significantly improved the prediction of ACS on top of obstructive CAD (C-index=0.790) (Figure 2A). On top of ischemic CAD (1967 patients, 66 events), all plaque types were also independent predictors of ACS (Figure 1B). But, similarly, according to the C-indexes (p-value vs. ischemic CAD), only PAV (C-index=0.818, p=0.003), and NCPB+LAP (C-index=0.818, p=0.005), but not CPB (C-index=0.798, p=0.054) significantly improved the prediction of ACS on top of ischemic CAD (C-index=0.776) (Figure 2B). NCPB+LAP alone performed similarly as PAV on top of obstructive (p=0.554) and ischemic CAD (p=0.991) (Figure 2). Conclusions Among patients with native coronary arteries treated medically, AI-based plaque quantification significantly improved the prediction of ACS on top of obstructive or ischemic CAD. The risk of ACS was largely related to NCPB+LAP, whereas CPB did not significantly improve risk stratification.Adjusted HR for ACS per plaque typeC-indexes for ACS

Influence of coronary plaque characteristics on lesion-specific ischemia assessed by coronary computed tomography angiography and fractional flow reserve - a systematic review and meta-analysis

Abstract Background Characterization of atherosclerotic plaque features by coronary computed tomography angiography (CCTA) carries profound prognostic value. Previous studies indicate that coronary plaque burden and certain plaque features are associated to lesion-specific ischemia by invasive fractional flow reserve (FFR). However, the existing literature is limited by small sample sizes, and provide inconsistent results. Purpose We performed a meta-analysis in order to delineate further the potential association between coronary plaque phenotype by CCTA and FFR. Methods A comprehensive systematic literature review and meta-analysis was conducted. PubMed and Embase databases were searched for studies that investigated the association between coronary plaque characteristics and FFR between January 2010 and August 2023. Study search, evaluation, and data extraction were performed independently by two researchers. Weighted mean difference (WMD) method for WMD was used for comparison of pooled per-lesion plaque parameters and presence of specific plaque features against presence of lesion-specific ischemia (FFR ≤0.80). Lesions with stenosis severity of 25-90% were included. Extracted data from eligible studies were analysed using random effects model for WMD and to estimate odds ratios (OR) with 95% confidence intervals (CI). Results A total of 12 studies were deemed eligible with 1,318 patients and available data on 1,915 coronary lesions. Of these, 626 lesions caused ischemia. Significantly greater total plaque volume (TPV) and non-calcified plaque volume (NCPV) occurred in lesions with abnormal FFR compared to normal FFR (WMD 83.0 mm3, 95% CI: 44.27; 121.81, p&amp;lt;0.001; WMD 83.63 mm3, 95% CI: 55.0; 112.24, p &amp;lt;0.001, respectively). Similar findings were observed for aggregate plaque volume (%APV) and plaque burden (%PB) with WMD 9.18, 95% CI: 6.08; 12.28, p&amp;lt;0.001; WMD 8.83, 95% CI: 4.32; 14.24, p=0.001, respectively. Napkin ring-sign and spotty calcification appeared more frequent in ischemia-causing lesions compared to those with FFR &amp;gt;0.80 (OR 4.25, 95% CI: 1.39; 13.00, p=0.011; OR 1.92, 95% CI: 1.33; 2.75, p=0.001, respectively). A summary of the meta-analysis findings regarding the association between plaque burden and plaque characteristics and FFR is provided in Figure 1 and 2. Conclusion CCTA-derived TPV and NCPV as well as %APV, %PB and the presence of napkin-ring sign and spotty calcification are associated with presence of lesion-specific ischemia. Coronary plaque assessment from CCTA images provide improved discrimination of lesion-specific ischaemia.

Impact of hypertension on coronary artery plaques and FFR-CT in type 2 diabetes mellitus patients: evaluation utilizing artificial intelligence processed coronary computed tomography angiography.

This study utilized artificial intelligence (AI) to quantify coronary computed tomography angiography (CCTA) images, aiming to compare plaque characteristics and CT-derived fractional flow reserve (FFR-CT) in type 2 diabetes mellitus (T2DM) patients with or without hypertension (HTN). A retrospective analysis was conducted on 1,151 patients with suspected coronary artery disease who underwent CCTA at a single center. Patients were grouped into T2DM (n = 133), HTN (n = 442), T2DM (HTN+) (n = 256), and control (n = 320). AI assessed various CCTA parameters, including plaque components, high-risk plaques (HRPs), FFR-CT, severity of coronary stenosis using Coronary Artery Disease Reporting and Data System 2.0 (CAD-RADS 2.0), segment involvement score (SIS), and segment stenosis score (SSS). Statistical analysis compared these parameters among groups. The T2DM (HTN+) group had the highest plaque volume and length, SIS, SSS, and CAD-RADS 2.0 classification. In the T2DM group, 54.0% of the plaque volume was noncalcified and 46.0% was calcified, while in the HTN group, these values were 24.0 and 76.0%, respectively. The T2DM (HTN+) group had more calcified plaques (35.7% noncalcified, 64.3% calcified) than the T2DM group. The average necrotic core volume was 4.25 mm3 in the T2DM group and 5.23 mm3 in the T2DM (HTN+) group, with no significant difference (p > 0.05). HRPs were more prevalent in both T2DM and T2DM (HTN+) compared to HTN and control groups (p < 0.05). The T2DM (HTN+) group had a higher likelihood (26.1%) of FFR-CT ≤0.75 compared to the T2DM group (13.8%). FFR-CT ≤0.75 correlated with CAD-RADS 2.0 (OR = 7.986, 95% CI = 5.466-11.667, cutoff = 3, p < 0.001) and noncalcified plaque volume (OR = 1.006, 95% CI = 1.003-1.009, cutoff = 29.65 mm3, p < 0.001). HRPs were associated with HbA1c levels (OR = 1.631, 95% CI = 1.387-1.918). AI analysis of CCTA identifies patterns in quantitative plaque characteristics and FFR-CT values. Comorbid HTN exacerbates partially calcified plaques, leading to more severe coronary artery stenosis in patients with T2DM. T2DM is associated with partially noncalcified plaques, whereas HTN is linked to partially calcified plaques.

Improved diagnostic accuracy of vessel-specific myocardial ischemia by coronary computed tomography angiography (CCTA)

BackgroundDiscrepancies between stenosis severity assessed at coronary computed tomography angiography (CCTA) and ischemia might depend on vessel type. Coronary plaque features are associated with ischemia. Thus, we evaluated the vessel-specific correlation of CCTA-derived diameter stenosis (DS) and invasive fractional flow reserve (FFR) and explored whether integrating morphological plaque features stratified by vessel might increase the predictive yield in identifying vessel-specific ischemia. MethodsObservational cohort study including patients undergoing CCTA for suspected coronary artery disease, with at least one vessel with DS ​≥ ​50 ​% at CCTA, undergoing invasive coronary angiography and FFR. Plaque analysis was performed using validated semi-automated software. Coronary vessels were stratified in left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA). Per vessel independent predictors of ischemia among CCTA-derived anatomical and morphologic plaque features were tested at univariable and multivariable logistic regression analysis. The best cut-off to predict ischemia was determined by Youden's index. Ischemia was defined by FFR≤0.80. ResultsThe study population consisted of 192 patients, of whom 224 vessels (61 ​% LAD, 19 ​% LCX, 20 ​% RCA) had lesions with DS ​≥ ​50 ​% interrogated by FFR. Despite similar DS, the rate of FFR≤0.80 was higher in the LAD compared to LCX and RCA (67.2 ​% vs 43.2 ​% and 44.2 ​%, respectively, p ​= ​0.018). A significant correlation between DS and FFR was observed only in LAD (p ​= ​0.003). At multivariable analysis stratified by vessel, the vessel-specific independent predictors of positive FFR were percent atheroma volume (threshold>17 ​%) for LAD, non-calcified plaque volume (threshold >130 ​mm3) for LCX, and lumen volume (threshold <844 ​mm3) for RCA. Integrating DS and vessel-specific morphological plaque features significantly increased the predictive yield for ischemia compared to DS alone (AUC ranging from 0.51 to 0.63 to 0.76–0.80). ConclusionsIntegrating DS and vessel-specific morphological plaque features significantly increased the predictive yield for vessel-specific ischemia compared to DS alone, potentially improving patients’ referral to the catheterization laboratory.

Interscan reproducibility of computed tomography derived coronary plaque volume measurements

BackgroundCoronary computed tomography angiography (CCTA) enables detailed quantification and characterization of coronary atherosclerotic plaques, offering diagnostic and prognostic value. Interscan reproducibility studies on plaque volume measurements are limited. This study aims to assess the interscan reproducibility of coronary plaque quantification and the implications of clinical and technical characteristics on interscan reproducibility. MethodsCCTA was performed twice in 101 patients with known coronary artery disease at a 1-h interval. The scans were conducted using identical CCTA acquisition protocols. Coronary plaque volumes were quantified using a semi-automated software and performed on a per-lesion, per-vessel, and per-patient level. ResultsMedian plaque volumes were comparable between the first and second CCTA scan. Interscan correlation was high for total plaque (TP), non-calcified plaque (NCP), and calcified plaque (CP) across all analyses (Pearson's coefficient 0.93–0.99), but lower for low-density non-calcified plaque (LD-NCP) volume measurements (Pearson's coefficient 0.74–0.77). Bland-Altman analyses demonstrated higher interscan agreement on a per-patient level compared to on per-vessel and per-lesion level. Interscan reproducibility on CP volumes was affected by CT image quality with narrower LoA in scans with the highest image quality score (p ​= ​0.003), or lowest image reconstructive iteration level (p ​< ​0.001). Limits of agreement were significantly narrower for TP, NCP, and CP volumes in LAD-lesions and vessels compared to non-LAD lesions and vessels (p ​≤ ​0.001). ConclusionOverall reproducibility of repeated CCTA derived plaque measurements by a semi-automated software was modest, and was influenced by image quality, image reconstruction settings, and lesion location.