Plaque Characteristics Research Articles

Plaque characterization and individualized risk assessment

Risk assessment and accurate plaque characterization are key to individual prognosis in coronary artery disease (CAD). The standard of care is cardiac computed tomography (CT), including calcium scoring and coronary CT angiography (CCTA). Diagnosis is based on the CAD-RADS (Coronary Artery Disease-Reporting and Data System) classification. New developments include CT-based fractional flow reserve (CT-FFR) and plaque quantification ("virtual histology"). Acalcium score of0 indicates an event risk of less than 1% over 10years [7, 17]. CAD-RADS classes1 to5 allow risk assessment compared to patients without coronary plaques [2]. CT-FFR has high accuracy (area under the curve [AUC] 0.90; 95% confidence interval 0.87-0.94) in assessing the hemodynamic significance of stenoses compared with invasive coronary angiography [25]. Plaque quantification has shown that anecrotic core greater than 4% is associated with an almost fivefold increase in 5‑year event risk [29]. The presence of obstructive CAD (stenosis > 50%) is astrong prognostic factor. The evaluation of the hemodynamic relevance of 40-90% stenoses by CT-FFR or other functional tests is already guideline-compliant in the USA, but not yet in Germany. Quantitative approaches to measure plaque volume and composition are gaining importance in research and are expected to become relevant in clinical practice. The CAD-RADS 2.0 classification, which also provides therapy recommendations, should be used to assess the extent of CAD.

Abstract 4137243: Dynamic changes of pericoronary fat attenuation index predicting changes of coronary plaque burden

Background: Percent atheroma volume (PAV) is a validated index of coronary plaque burden, linking to adverse cardiac events. Meanwhile, pericoronary fat attenuation index (FAI) on coronary computed tomography angiography (CCTA) image is a novel prognostic marker of coronary inflammation. Research Questions: It is unknown the impact of coronary inflammation (i.e., FAI) on the progression of coronary PAV in patients at an increased risk of adverse cardiac events. Methods: Patients with type 2 diabetes mellitus (T2DM) who underwent at least two clinically indicated CCTA examinations (time interval > 1 year) at our center were potentially eligible for enrollment. Eligible patients presented with more than one study plaque, defined as non-obstructive stenosis at baseline and not being intervened during serial CCTA. Longitudinal CCTA images were assessed for FAI and compositional plaque characteristics (e.g., PAV) using dedicated post-processing softwares. The relationships between changes in FAI and progression of compositional PAV were examined using the logistic and linear regression analysis. Results: A total of 204 T2DM patients (mean age, 61.2 ± 9.3 years; male, 68.1%) with 366 study plaques were enrolled. All patients were treated with statins, and their time interval between longitudinal CCTAs was 14.1 (12.9, 17.6) months. Compared with patients with improved coronary inflammation (ΔFAI ≤ 0), those with deteriorated coronary inflammation (ΔFAI > 0) had lower high density lipoprotein cholesterol and baseline FAI, whereas higher blood pressure (all p < 0.05). Meanwhile, compared to patients with ΔFAI ≤ 0, those with ΔFAI > 0 had more Δoverall and Δnon-calcified PAV (all p < 0.05). Importantly, these findings were consistent in a dedicated propensity score matching analysis. In logistic regression analysis, ΔFAI > 0 was associated with annual progression of overall PAV and non-calcified PAV, whereas ΔFAI ≤ 0 associated with annual regression of overall PAV and non-calcified PAV after adjusting for cardiac risk factors, baseline PAV and medications (all p < 0.05). Similarly, in linear regression analysis, changes of FAI were independently positively associated with annual changes of overall PAV (β=0.545, p< 0.001) and non-calcified PAV (β=0.461, p< 0.001) (Figure 1). Conclusion: In this longitudinal CCTA study, changes of coronary inflammation are closely correlated with changes of overall and non-calcified PAV among T2DM patients treated with statins.

Abstract 4137782: Fibrinogen-to-Albumin Ratio Does Not Correlate with Comprehensively Assessed Coronary Artery Disease Severity or High-Risk Plaque Features on Coronary Computed Tomographic Angiography

Background: Fibrinogen-to-albumin ratio (FAR) has been proposed as a readily available inflammatory biomarker associated with coronary artery disease (CAD). However, its association with CAD severity and prognosis has predominantly been assessed in patients with acute coronary syndromes (ACS). The Leiden score is a validated comprehensive measure of CAD incorporating stenosis proximity, severity, and plaque type that independently predicts cardiovascular events. Whether FAR is associated with Leiden score or high-risk plaque features on coronary computed tomographic angiography (CCTA) in stable outpatients is unknown. Methods: Adult outpatients undergoing clinically indicated CCTA were enrolled (5/2021-9/2023) in a prospective study assessing the relationship of plaque to immune markers and provided same-day pre-scan peripheral venous blood samples. CCTAs were post-processed and analyzed by the consensus of two expert readers blinded to clinical data using a 17-segment model to determine coronary artery calcium (CAC), Leiden score, and high-risk plaque features. Patients were grouped by FAR (quartiles), Leiden score (<5, 5-20, >20), and CAC score (0, >0-100, >100-300, >300-1000, >1000). Numerical variables were compared via Wilcoxon and Kruskal-Willis tests. Spearman correlation was calculated between FAR and Leiden score. Results: Of 284 patients, 53.8% were male, 86.7% were white, and 58.8% were on a statin (Table 1). Median FAR was 70.3 mg/g, 64.0% had a non-zero CAC score, and 25.0% had at least one segment with one high-risk plaque feature. Across quartiles of FAR, there was no difference in Leiden score (5.8 (IQR: 0.0-18.5), 12.4 (3.1-20.7), 8.0 (0.0-19.9), 6.8 (0.0-21.1), p=0.50) or probability of having at least one segment with at least one (29.6%, 23.9%, 23.9%, 22.5%, p=0.69) or two (18.3%, 14.1%, 12.7%, 15.5%, p=0.66) high-risk plaque features. There was no correlation between FAR and Leiden score (R=0.03, p=0.66). There was no difference in FAR when stratified by Leiden score (Table 1, p=0.53), CAC score (Table 2, p=0.50), or number of segments with at least one high-risk plaque feature (Table 3, p=0.18). Conclusion: In a prospective cohort of adult outpatients across a wide spectrum of CAD burden with high rates of baseline statin use, FAR was not associated with CAD or presence of high-risk plaque features on CCTA. Further evaluation of its role as an inflammatory biomarker in larger populations, particularly patients without ACS, is required.

High-risk features in non-culprit lesions and clinical outcome after NSTEMI versus STEMI.

Complete non-culprit (NC) revascularization may help reduce recurrent events after NSTEMI, especially if NC lesions would harbor high-risk plaque features similar to STEMI. The study aimed to assess differences in fractional flow reserve (FFR)-negative NC plaque morphology in patients presenting with NSTEMI versus STEMI and assess the association of high-risk plaque morphology and clinical outcome. In the prospective PECTUS-obs study, 438 patients presenting with myocardial infarction (MI) underwent optical coherence tomography (OCT) of all FFR-negative intermediate NC lesions. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE, all-cause mortality, non-fatal MI or unplanned revascularization) at two-year follow-up. Four hundred and twenty patients had at least one analyzable OCT, including 203 (48.3%) with NSTEMI and 217 (51.7%) with STEMI. The prevalence of high-risk plaques (HRP), including thin-cap fibroatheromas (TCFA), plaque rupture and thrombus, was comparable between groups. MACE occurred in 29 (14.3%) NSTEMI patients and 16 (7.4%) STEMI patients (Punivariable=0.025 and Pmultivariable=0.270). Incidence of MACE was numerically higher among patients with HRP, irrespective of the clinical presentation at index (Pinteraction=0.684). Among high-risk plaque criteria, plaque rupture was associated with MACE in both NSTEMI (p<0.001) and STEMI (p=0.020). Presence of NC HRP is comparable between NSTEMI and STEMI and leads to numerically higher event rates in both. These results call for additional research on complete revascularization in NSTEMI and treatment of HRP.

Artificial intelligence applied to coronary artery calcium scans (AI-CAC) significantly improves cardiovascular events prediction

Coronary artery calcium (CAC) scans contain valuable information beyond the Agatston Score which is currently reported for predicting coronary heart disease (CHD) only. We examined whether new artificial intelligence (AI) applied to CAC scans can predict non-CHD events, including heart failure, atrial fibrillation, and stroke. We applied AI-enabled automated cardiac chambers volumetry and calcified plaque characterization to CAC scans (AI-CAC) of 5830 asymptomatic individuals (52.2% women, age 61.7 ± 10.2 years) in the multi-ethnic study of atherosclerosis during 15 years of follow-up, 1773 CVD events accrued. The AUC at 1-, 5-, 10-, and 15-year follow-up for AI-CAC vs. Agatston score was (0.784 vs. 0.701), (0.771 vs. 0.709), (0.789 vs. 0.712) and (0.816 vs. 0.729) (p < 0.0001 for all), respectively. AI-CAC plaque characteristics, including number, location, density, plus number of vessels, significantly improved CHD prediction in the CAC 1–100 cohort vs. Agatston Score. AI-CAC significantly improved the Agatston score for predicting all CVD events.

Natural history of a newly developed calcified nodule: incidence, predictors, and clinical outcomes.

Calcified nodules (CNs) are an increasingly important, high-risk lesion subset. We sought to identify the emergence of new CNs and the relation between underlying plaque characteristics and new CN development. Patients who had undergone two optical coherence tomography (OCT) studies that imaged the same untreated calcified lesion at baseline and follow-up were included. New CNs were an accumulation of small calcium fragments at follow-up that were not present at baseline. Cardiac death, myocardial infarction (MI), or clinically driven revascularisation related to OCT-imaged, but untreated, calcified lesions were then evaluated. Among 372 untreated calcified lesions, with a median of 1.5 (first and third quartiles: 0.7-2.9) years between baseline and follow-up OCTs, new CNs were observed in 7.0% (26/372) of lesions at follow-up. Attenuated calcium representing residual lipid (odds ratio [OR] 3.38, 95% confidence interval [CI]: 1.15-9.98; p=0.03); log10 calcium volume index (length×maximum arc×maximum thickness; OR 2.76, 95% CI: 1.10-6.95; p=0.03); angiographic Δangle between systole and diastole, per 10° (OR 2.30, 95% CI: 1.25-4.22; p=0.01); and time since baseline OCT, per year (OR 1.36, 95% CI: 1.05-1.75; p=0.02) were all associated with new CN development. Clinical events were revascularisation and/or MI and were more frequent in lesions with versus without a new CN (29.3% vs 15.3%; p=0.04). New CNs developed in untreated, lipid-containing, severely calcified lesions with a larger angiographic hinge motion (between systole and diastole), compared with lesions without CNs, and were associated with worse clinical outcomes.

Association of coronary inflammation with plaque vulnerability and fractional flow reserve in coronary artery disease

BackgroundThe fat attenuation index (FAI) measured using coronary computed tomography angiography (CCTA) enables the direct evaluation of pericoronary adipose tissue composition and vascular inflammation. We aimed to investigate the association of fractional flow reserve (FFR) and plaque vulnerability with coronary inflammation. MethodsPatients with suspected coronary artery disease (CAD) who underwent CCTA and invasive FFR measurements within 90-day were included. A cloud-based medical device, CaRi-Heart, serves as a surrogate tool for evaluating coronary inflammation based on FAI by analyzing CCTA images. The correlations between CCTA-defined plaque characteristics, invasive coronary angiographic and physiologic assessments, and CaRi-Heart risk were analyzed. The primary endpoint was the patient-oriented composite outcome (POCO) consisting of all-cause death, any myocardial infarction, and any revascularization. ResultsA total of 564 patients (median age 67.0 years; 75.4 ​% men) were included. There were no significant differences in quantitative and qualitative plaque characteristics or FFR between the high- and low-CaRi-Heart risk groups (i.e., ≥5 ​% and <5 ​%). During the median follow-up of 3.2 years [1.13–4.73 years], CaRi-Heart risk ≥5 ​% was associated with a significantly higher rate of POCO compared to CaRi-Heart risk <5 ​% (0.9 ​% vs. 10.1 ​%, P ​= ​0.037). The CaRi-Heart risk was an independent predictor of POCO as a continuous (adjusted HR 1.016, 95 ​% CI 1.005–0.027, P ​= ​0.004) and categorical variable (CaRi-Heart risk ≥5 ​%, adjusted HR 2.949, 95 ​% CI 1.182–7.360, P ​= ​0.021), regardless of high-risk plaque characteristics and FFR. ConclusionCoronary inflammation risk assessed using CaRi-Heart risk provides independent prognostic information regardless of plaque vulnerability and physiologic stenosis in patients with CAD.

Morphological characterization of coronary plaques in young indian patients with acute coronary syndrome: A multicentric study

ObjectivesThe prevalence of atherosclerosis and acute coronary syndrome (ACS) is increasing in young Indians (18–50 years of age). However, the characteristics of atherosclerotic plaques in such individuals are poorly understood, presenting distinct challenges for the management of ACS. This study aims to analyze plaque characteristics in young Indian patients with ACS who underwent percutaneous coronary intervention (PCI) using optical coherence tomography (OCT) imaging. MethodsThis was a prospective, multicentric, non-interventional study on patients aged 18–50 years presenting with ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction, or unstable angina, and were scheduled to undergo OCT-guided PCI. Major adverse cardiac events (MACE) were assessed post-procedure and at the 6-month and 12-month follow-ups. ResultsThe study included 100 ACS patients (mean age = 43.6 ± 5.2 years), with 51% presenting with STEMI. Pre-PCI OCT assessment showed that fibrous plaques (75%) were most common followed by plaques containing macrophages (27%), microchannels (20%), and calcified nodules (14%). In addition, plaque rupture, plaque erosion, and lipid-rich plaques, along with red, white, and mixed thrombi, were observed in 31%, 25%, 24%, 21%, 14%, and 17% (total thrombus occurrence = 52%) of the patients, respectively. At 12 months, the MACE (coronary artery bypass graft) rate was 1%. ConclusionsYoung Indian patients with ACS displayed a range of plaque morphologies identified through pre-PCI OCT. Among these, fibrous plaques were the most prominent type, followed by plaques containing macrophages. Additionally, plaque rupture, plaque erosion, and lipid-rich plaques were also observed in this population.

Whys and Wherefores of Coronary Arterial Positive Remodeling.

Positive remodeling (PR) is an atherosclerotic plaque feature defined as an increase in arterial caliber at the level of an atheroma, in response to increasing plaque burden. The mechanisms that lead to its formation are incompletely understood, but its role in coronary atherosclerosis has major clinical implications. Indeed, plaques with PR have elevated risk of provoking acute cardiac events. Hence, PR figures among the high-risk plaque features that cardiac imaging studies should report. This review aims to provide an overview of the current literature on coronary PR. It outlines the pathophysiology of PR, the different techniques used to assess its presence, and the imaging findings associated to PR, on both noninvasive and invasive studies. This review also summarizes clinical observations, trials, and studies, focused on the impact of PR on clinical outcome.

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.

Clustering of artificial intelligence derived plaque features for risk stratification for future atrial fibrillation development

Abstract Introduction We previously demonstrated that artificial intelligence (AI)-derived coronary artery plaque features are associated with future development of atrial fibrillation (AF) among patients undergoing CCTA(1). Our results suggest that phenotyping a large dataset of plaque features using data science techniques may reveal associations not visible from univariate analysis. Purpose Use data science analysis of AI-CT plaque characteristics to identify subpopulations at higher risk of AF. Methods We applied dimensionality reduction and visual cluster identification to phenotype our population of patients based on their AI-CT plaque features. We used a single center CCTA registry of patients with prior clinically-indicated CCTA (N=2700) from 2017-2020. Cases of new AF were defined by onset of AF on ECG or telemetry after CCTA via EMR search. Patients with AF prior to CCTA, history of mitral valve surgery, or postoperative AF were excluded. Controls were selected 1:1 by nearest neighbor propensity matching (R. v. 4.0.3.) based on age, sex, tobacco use, HTN, HLD, and diabetes. Atherosclerotic plaques were quantitatively analyzed using a commercially available FDA-approved AI coronary analysis software yielding stenosis area and diameter, remodeling index, volume of calcified/non-calcified/low-density plaques, and number of 2 or more high risk plaques. Uniform Manifold Approximation and Projection (UMAP) dimensionality reduction with cosine distance metric was used to reduce the plaque feature space from 80 dimensions (8 AI measurements per each of 10 anatomical vessel segments in all patients) to 2 dimensions on a scatter plot. Two non-contiguous clusters (i.e. plaque phenotypes) were identified based on visual analysis of UMAP feature reduction (Figure 1). Results 94 cases comprised the study cohort (47 cases and 47 controls). Mean age was 67±11 years. 38% were female. Mean CADRADS score was 1.8±1.52 and mean CAC was 325±622. Mean time from CT to AF was 281±300 days. The majority of AF patients (67%) fell into Cluster 1 (N=36), while Cluster 2 (N=58) contained most of the control subjects (75%). Treating Cluster 1 as a predictor of AF, the PPV and specificity of the UMAP reduction was 67% and 75% respectively, with NPV of 60% and sensitivity of 51% (Table 1). Left atrial volume index (LAVI) was significantly different between the 2 clusters, with mean 56.15±12.42 ml/m2 in Cluster 1 and 46.96±16.03 in Cluster 2 (p=0.0046). LAVI was also significantly different between control subjects in Cluster 1 vs 2, mean 54.84±11.6 vs 41.62±7.92 (p&amp;lt;0.001). Conclusions We demonstrated that UMAP-derived clustering of AI-CT plaque characteristics identifies novel phenotypes for future risk of AF among patients undergoing CCTA. Further, control patients in Cluster 1 were found to have a significantly higher LAVI compared to control subjects in Cluster 2, which supports that membership in Cluster 1 may increase risk of future development of AF.

The impact of transcatheter aortic valve replacement on changes of coronary computed tomography-derived fractional flow reserve

Background The effect of transcatheter aortic valve replacement (TAVR) on changes of computed tomography-derived fractional flow reserve (CT-FFR) values was controversial. Thus, we aimed to identify the impact of TAVR on changes of CT-FFR values, plaque characteristics, and the associated clinical impact. Methods This single-center observational study included 39 consecutive patients with severe aortic valve disease undergone TAVR between August 2019 and April 2023, whom were performed with preoperative and postoperative coronary CT angiography (CCTA). The computation of CT-FFR and plaque characteristics was performed by an independent central core laboratory. Results Each patient underwent CCTA and CT-FFR assessment without encountering any complications. Notably, both at discharge and six months post-TAVR, there was a significant improvement observed in the New York Heart Association (NYHA) functional classification, left ventricular fractional shortening, and ejection fraction compared to pre-operative levels. The CT-FFR for left anterior descending artery (LAD), left anterior descending artery (LCX), and right coronary artery (RCA) had no obvious change at discharge compared to pre-operation (0.92 ± 0.05 vs. 0.93 ± 0.05, p = 0.109; 0.96 ± 0.03 vs. 0.95 ± 0.03, p = 0.523; 0.97 ± 0.04 vs. 0.97 ± 0.03, p = 0.533; respectively). Furthermore, TAVR did not exert a significant impact on plaque burden during the perioperative period. Conclusions Our report suggested that TAVR did not significantly affect coronary CT-FFR measurements and plaque characteristics in the perioperative period, and furthermore, the patients’ cardiac function showed gradual improvement in the short-term following discharge.

Trend in culprit plaque phenotype in ACS patients over the past 10 years

Abstract Background Although the incidence of acute myocardial infarction has been declining over the past decade, the etiology of this trend is unknown. One possible explanation could be changes in coronary plaque phenotype. Purpose The aim of this study was to investigate the changes in plaque characteristics over the last 10 years. Methods Patients who presented with acute coronary syndrome and underwent preintervention optical coherence tomography (OCT) imaging from 2008 to 2018 were included. Patients were divided into 4 periods: (P1) 2008-2010, (P2) 2011-2013, (P3) 2014-2015, and (P4) 2016-2018. Plaque characteristics at culprit lesion in each period were compared. Results Among 1144 patients, 594 (51.9%) presented with ST-segment–elevation myocardial infarction (STEMI). The prevalence of thin-cap fibroatheroma decreased from P1 to P4 in both STEMI group (57.4% to 24.6%, P&amp;lt;0.001) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) group (40.4% to 17.0%, P&amp;lt;0.001) (Figure). Conclusions The prevalence of OCT features of plaque vulnerability has decreased over the past 10 years. A decrease in plaque vulnerability may explain the favorable trend in cardiovascular events.Prevalence of thin-cap fibroatheroma

Plaque characteristics and long-term outcome of non-culprit plaque rupture in AMI patients

Abstract Background Non-culprit plaque rupture (PR) had widespread nature in patients with acute coronary syndrome, indicating generalized acute destabilization. However, morphological features and long-term outcomes of non-culprit PR in acute myocardial infarction (AMI) patients have not been systemically investigated. Objectives We aimed to investigate the pancoronary picture (plaque characteristics and location) and long-term outcomes of non-culprit PR in AMI patients. Methods From January 2017 to May 2019, 3757 non-culprit plaques were analyzed in 883 AMI patients treated by 3-vessel optical coherence tomography. Patients and lesions were divided into two groups based on the presence or absence of non-culprit PR. All patients enrolled were followed for up to four years. Results Non-culprit PR was found in 178 patients (20.2%) and 200 lesions (5.3%). Patients with non-culprit PR had a more non-culprit lesions (NCLs) (p &amp;lt; 0.001), diseased arteries (p &amp;lt; 0.001) and multi-vessel disease (p &amp;lt; 0.001) compared with patients without non-culprit PR, both in angiography and OCT analyses. In vulnerable plaque feature, non-culprit PR group had higher incidence of thin-cap fibroatheroma (TCFA) (p &amp;lt; 0.001; p &amp;lt; 0.001), minimal lumen area (MLA) &amp;lt; 3.5mm² (p = 0.004; p = 0.012), CLIMA-defined high-risk plaque (p &amp;lt; 0.001; p &amp;lt; 0.001), thrombus (p &amp;lt; 0.001; p &amp;lt; 0.001), lipid rich plaque (p &amp;lt; 0.001; p &amp;lt; 0.001), calcification (p &amp;lt; 0.001; p &amp;lt; 0.001), macrophage (p &amp;lt; 0.001; p &amp;lt; 0.001), microchannel (p &amp;lt; 0.001; p &amp;lt; 0.001), cholesterol crystals (p &amp;lt; 0.001; p &amp;lt; 0.001), and layered tissue (p &amp;lt; 0.001; p &amp;lt; 0.001) compared with the other group, in patient and lesion level. In addition, non-culprit PR was highly populated at "hot spots" in the right coronary artery (56.5% vs. 40.2%; p &amp;lt; 0.001), and the originally treated culprit artery (33.5% vs. 25.2%; p = 0.008), and tended to cluster proximal to the coronary ostium [26.1 (15.5-38.0) vs. 29.4 (15.8-44.5); p = 0.009]. Multivariate analysis identified the NCL in the initially treated culprit artery (odds ratio [OR]: 1.874, 95% confidence interval [CI]: 1.230–2.857, p = 0.003), distance from coronary ostium to MLA site (OR: 0.987, 95% CI: 0.978–0.997, p = 0.008), mean lipid arc (OR: 1.006, 95% CI: 1.003–1.010, p = 0.001), TCFA (OR: 15.870, 95% CI: 10.259–24.551, p &amp;lt; 0.001), thrombus (OR: 4.333, 95% CI: 2.346–8.003, p &amp;lt; 0.001), and microchannel (OR: 1.679, 95% CI: 1.136–2.482, p = 0.009) were independent predictors of non-culprit PR. Non-culprit PR showed higher 4-year rates of NCL-related major adverse cardiac events in the patient (14.0% vs. 5.1%; p = 0.001) and lesion (6.5% vs. 0.9%; p &amp;lt; 0.001) levels. Conclusions NCLs with non-culprit PR had a unique pancoronary picture (pancoronary vulnerability and "hot spots") and worse long-term outcomes in AMI patients.

Predictive value of plaque characteristics assessed by coronary computed tomography angiography and optical coherence tomography for identification of lesions causing ischemia

Abstract Background In patients with intermediate coronary stenosis, the functional assessment with fractional flow reserve (FFR) and the anatomical assessment with optical coherence tomography (OCT) have been widely used in clinical practice. Additionally, coronary computed tomography angiography (CTA) is commonly used non-invasive imaging technique for evaluating suspected coronary artery disease before being referred for angiography. Objectives This study sought to investigate the association between FFR and plaque characteristics assessed by coronary CTA and OCT in intermediate coronary stenosis. Methods Based on the prospective multicentre registry, a total of 159 patients including 339 coronary lesions with intermediate stenosis were included. All patients underwent coronary CTA before being referred for coronary angiography and both FFR measurement and OCT examination were performed during angiography. The stenotic lesion with FFR ≤0.80 was considered diagnostic of lesion causing ischemia. The predictive value of plaque characteristics assessed by coronary CTA and OCT for identifying lesions causing ischemia was analyzed. Results Stenosis severity and plaque characteristics on coronary CTA and OCT were different between the lesions causing ischemia versus not causing ischemia. On multivariate analysis, low attenuation plaque on coronary CTA (odds ratio [OR]= 2.78; P=0.038) and thrombus (OR=5.13; 0.042), plaque rupture (OR=3.25; P=0.017), and intimal vasculature on OCT (OR=2.57; P=0.012) were independent predictors for the lesions causing ischemia. Increasing number of these plaque characteristics offered incremental improvement in predicting the lesions causing ischemia. Conclusions Comprehensive anatomical evaluation of coronary stenosis may be able to provide additional supportive information for predicting the lesions causing ischemia.

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.

Prediction of the burden and characteristics of coronary plaques by cardiorespiratory fitness

Abstract Background Cardiorespiratory fitness (CRF) and coronary plaque burden are both important predictors of mortality. Although mortality of coronary heart disease (CHD) is reduced, prevalence remains high and there is a need to improve early detection and preventive measures. How CRF relates to coronary plaque burden and composition in the general population is largely unknown. Purpose The aim was to study the relationship between CRF and the total coronary plaque burden, including subgroups of coronary plaques, in subjects without known CHD. Methods A random sample of participants from a large population-based echocardiographic reference range study aged 55-70 at baseline was included. Coronary plaque burden was assessed, on average, 4.0 years after the baseline evaluation using coronary computed tomography angiography (CCTA). The burden and characteristics of the coronary plaques were evaluated using a validated, commercially available, semi-automatic software that assessed all coronary territories including the left main, left anterior descending, circumflex, and right arteries. Coronary plaques were classified as dense calcified plaques, plaques with necrotic core, fibrous, and fibrous-fatty plaques. Baseline measures included cardiovascular risk factor assessment and measurement of peak oxygen consumption (VO2peak) assessed by treadmill cardiopulmonary exercise testing. Linear regression models were used to assess the impact of VO2peak on coronary plaque burden. In Model 1, we adjusted for sex and age, while Model 2 also included adjustments for non-HDL cholesterol, HbA1c, systolic blood pressure, smoking status, and body mass index. Results Of 845 invited to undergo CCTA, 707 (51% females) underwent CT scanning. Of these, 699 scans had acceptable quality for further analyses. Table 1 shows baseline characteristics and Table 2 shows the associations of VO2peak with coronary plaque burden. In the fully adjusted Model 2, there was a significant negative association of VO2peak with total plaque burden (β -0.18, R2 15%, p&amp;lt;0.001), while the association was not significant in Model 1 (p=0.54). Similarly, higher VO2peak significantly predicted a lower burden of dense calcified plaques, plaques with necrotic core, and fibrofatty plaques in both models (R2 3-17%, p≤0.01). The results were consistent whether the coronary plaques were evaluated across the entire coronary arteries (down to a diameter of 1.5 mm) or solely in the proximal segments. However, the predictive power of the models was relatively low with R2 of maximum 17%. Conclusion In a population without known CHD, CRF explained a modest part of the variation in coronary plaque burden. Considering CRF in risk prediction may enhance coronary artery disease prevention beyond traditional risk factors.

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.

Mortality risk in patients with carotid artery disease undergoing carotid endarterectomy compared to the general population

Abstract Background Patients with carotid artery disease undergoing carotid endarterectomy (CEA) appear to be at high risk of all-cause mortality during their follow-up. However, the possible predictors of this adverse outcome are not elucidated yet. Purpose We aimed to test cardiovascular (CV) risk factors as possible predictors of all-cause mortality in patients undergoing CEA and to determine whether there is a difference between the mortality rate of our study cohort and the general population. We hypothesize that CEA-treated patients have a higher mortality rate during follow-up after surgery than the general population, which is not related to the presence of CV risk factors. Methods We prospectively enrolled and followed up patients undergoing CEA. Univariate and multivariable Cox regression were performed to test whether common CV risk factors (demographics, laboratory values, comorbidities, and events before CEA) were predictive of all-cause mortality. We then compared the standardized mortality ratio (SMR) of our population and the age-sex-matched Minnesota (MN) general population at 5,10, and 21 years of follow-up after CEA. Results A total of 710 patients were followed for a median of 7.1 [2.9-11.9] years after CEA. Mortality occurred in 198 (27.0%) patients during the follow-up. The median time to event was 11.0 [10.0-12.0] years. Age was the only predictor of all-cause mortality in CEA-treated patients in multivariable models adjusted for known CV risk factors (Model 1: HR 1.03 [95%CI 1.01-1.06]; p=0.004; Model 2: HR 1.02 [95%CI 1.00-1.04]; p=0.023) (Table 1). However, the CEA-treated group had a higher mortality rate than would have been expected in the MN population (log-rank p&amp;lt;0.001) (Fig.1A). Compared to the MN population, at 5 years of follow-up only patients &amp;lt;60 years old had a higher SMR (4.53 [1.95-8.92]; p=0.001), whereas, at 10 years and 21 years of follow-up, our study population had a higher mortality rate at any age (Fig.1B). Conclusions The elevated mortality risk post-CEA in our cohort cannot be solely attributed to chronological aging. The underlying process of atherosclerosis likely contributes to all-cause mortality, and plaque characteristics may offer additional insight into the risk stratification of this patient group.All cause mortality predictors after CEAStudy population vs. MN population SMR

Coronary artery plaque characteristics in smokers assessed by intracoronary multi-modality imaging: a NIRS-IVUS guided PROSPECT II substudy

Abstract Background Smoking is a risk factor for coronary artery disease and myocardial infarction. Purpose Among patients with myocardial infarction, we hypothesized smokers would have increased prevalence of nonculprit high-risk plaque characteristics as assessed by intracoronary multimodality imaged when compared to nonsmokers. Method This is a prespecified post-hoc analysis of the PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree). Altogether 898 patients with acute myocardial infarction with or without ST-segment elevation who after successful percutaneous coronary intervention had near-infrared spectroscopy and intravascular ultrasound imaging performed. Data on lesion location, plaque burden, and lipid content were collected. Current, former, and nonsmokers were examined regarding the presence of high-risk plaques in both culprit and nonculprit lesions as well as plaque location. High-risk plaque characteristics were defined as a maximum plaque burden (maxPB) of ≥70% and a maximum 4 mm lipid core burden index (maxLCBI4mm) of ≥324.7. Results Out of 886 patients with known smoking history, 32% were smokers, 32% former, and 37% nonsmokers. Smokers were younger (median age: smokers 59.0; former 65.5; nonsmokers 64.0 years, p&amp;lt;0.001) with fewer co-morbidities and presented more often with STEMI (% presenting with STEMI: smokers 22.2%; former 18.9%; nonsmokers 19.4%, p=0.006). LDL was similar but CRP was higher in smokers (median µg/mL: smokers 4.0; former 3.1; nonsmokers 2.9, p=0.004). In multivariate models of nonculprit lesion morphology smoking history was not associated with maxPB or maxLCBI4mm but was associated with presence of calcified nodules (OR: 2.88 (95% CI 1.46–5.69) p=0.002 [smokers vs nonsmokers]). Calcified nodules were also associated with number of years smoked (OR: 1.02 (95% CI 1.01–1.03) p=0.004). Smoking was not associated with presence of ≥1 lesions with MaxLCBI4mm, ≥ 324.7, maxPB &amp;gt;=70% or the combination of both. Smoking was not associated with presence of plaque rupture or thrombus. Right coronary artery culprit lesions were more common in smokers and former smokers (smokers 29.9%; former 30.9%; nonsmokers 21.6%; OR: 1.12 (95% CI 1.04–1.21) p&amp;lt;0.001 [smokers vs nonsmokers]). Conclusion In this prospective intracoronary multimodality imaging study of patients with recent acute myocardial infarction, smoking was not associated with a higher rate of high-risk nonculprit plaques based on lipid content by NIRS or PB by IVUS when compared to former or nonsmokers. However, smoking was associated with higher presence of IVUS-detected calcified nodules, higher CRP-levels, and the right coronary artery as it angiographically was a more common site for culprit lesions. These results indicate that the elevated risk in smokers is unrelated to vulnerable plaque morphology defined by high PB and lipid content, and instead possibly related to inflammation, calcification, or hemodynamic changes.Table 1