Coronary Atheroma Research Articles

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 > 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 > 100 AU, 9% had a stenosis > 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<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

Angioprotein-like 3 and atheroma progression in statin-treated type 2 diabetic patients with coronary artery disease: the pre-specified analysis from the OPTIMAL randomized controlled trial

Abstract Introduction Despite guideline-recommended control of LDL-C with a statin, type 2 diabetic patients more likely cause cardiovascular events. This indicates the need to identify additional therapeutic targets in those patients. Angioprotein-like 3 (ANGPTL3) is an inhibitor of lipoprotein and endothelial lipase, which increases the levels of LDL-C and other atherogenic lipoproteins. These properties suggest ANGPTL3 as a potential driver associated with diabetic atherosclerosis. The OPTIMAL randomized controlled trial (jRCT1052180152) compared the efficacy of continuous glucose monitoring-guided versus HbA1c-guided glycemic control on coronary atherosclerosis in statin-treated type 2 diabetic patients by using serial intravascular ultrasound (IVUS) imaging. This pre-specified analysis of the OPTIMAL study was designed to evaluate whether ANGPTL3 affects progression of coronary atheroma in statin-treated type 2 diabetic patients. Purpose To elucidate the association of serial change in ANGPTL3 with the degree of atheroma progression in statin-treated type 2 diabetic patients. Methods 59 patients (59 lesions) with serial ANGPTL3 levels at baseline and week 48 were included into the current analysis. Clinical demographics and IVUS-derived measure were compared in patients with and without any increase in ANGPTL3. Results All of study subjects received a statin, and over 60% of them were treated with high-intensity statin. Under these lipid-lowering therapies, any increase in ANGPTL3 levels at week 48 was observed in 52.5% of study participants. Patients with any increase in ANGPTL3 were more likely to have a history of hypertension (90.0% vs. 64.3%, p=0.02), whereas there was no significant difference in on-treatment LDL-C levels between the two groups (1.8 ± 0.4 vs. 1.6 ± 0.6 mmol/L, p=0.25) (Table). On IVUS imaging analysis, baseline percent atheroma volume (PAV) did not differ in those with and without any increase in ANGPTL3. However, patients with any increase in ANGPTL3 presented a greater progression of PAV (0.08 ± 0.28 vs. -0.74 ± 0.29, p=0.04). There was a trend toward a lower frequency of PAV regression in those exhibiting any increase in ANGPTL3 (48.4% vs. 57.1%), but this comparison did not meet statistical significance (p=0.50) (Figure). Multivariate analysis adjusting clinical characteristics demonstrated that any increase in ANGPTL3 level was not independently associated with PAV progression (β=0.16, 95%CI=-0.01 – 0.18, p=0.27). Conclusion Over 50% of statin-treated type 2 diabetic patients with coronary atherosclerosis showed any increase in ANGPTL3 levels at week 48. Serial IVUS imaging revealed that patients with any increase in ANGPTL3 more likely presented a greater atheroma progression. However, this relationship did not exist after adjusting clinical characteristics. Our findings suggest that ANGPTL3 may not be a pivotal driver associated with atheroma progression in statin-treated type 2 diabetic patients.

Apolipoprotein B and the regression of lipidic plaque in statin-treated type 2 DM patients with coronary artery disease: the pre-specified sub-analysis from the OPTIMAL randomized controlled trial

Abstract Introduction Type 2 diabetic mellitus (T2DM) patients more likely present vulnerable form of diseases. Despite lowering LDL-C level with a statin, their on-going cardiovascular risks still exist, which indicates the need to identify additional therapeutic targets in T2DM patients. Apolipoprotein B (ApoB) is a proatherogenic lipoprotein. Atherosclerosis is promoted via the influx of ApoB into vessel wall. The current ESC guideline recommends ApoB levels as a secondary therapeutic target under control of LDL-C levels with a statin. However, it remains to be fully determined about the association of ApoB levels with plaque vulnerability in statin-treated T2DM patients. Purpose To elucidate whether serial change in ApoB levels affects the degree of atheroma progression and lipidic plaque materials on NIRS/IVUS imaging. Methods The OPTIMAL randomized controlled trial compared the efficacy of continuous glucose monitoring guided versus HbA1c-guided glycemic control on coronary atherosclerosis in 94 statin-treated T2DM patients with CAD. Serial NIRS/IVUS imaging was conducted at baseline and week 48 to monitor non-culprit lesions. The current study included 71 patients with serial ApoB levels at both baseline and week 48. Clinical demographics and NIRS/IVUS-derived measures were compared in those with and without any reduction of ApoB levels. Results All of study subjects received a statin, and over 60% of them were treated with high-intensity statin. Under these lipid-lowering therapies, 60.6% of study subjects exhibited any reduction of ApoB levels, accompanied by a greater reduction of LDL-C levels. Patients with any reduction of ApoB levels were more likely to be older (67.4±10.0 vs. 71.7±7.3 years, p=0.03), whereas there were no significant differences in the proportion of established risk factors between the two groups. Baseline NIRS/IVUS-derived PAV (47.1±12.9 vs. 44.8±15.4%, p=0.54) and maxLCBI4mm [290.5 (205.5, 338.7) vs. 270.0 (97.0, 416.0), p=0.76] were comparable in patients with and without any reduction of ApoB. On serial NIRS/IVUS imaging analysis, the progression rate of atheroma volume did not differ between the two groups (-0.4±0.2 vs. -0.3±0.2mm3, p=0.77). However, patients with any reduction of ApoB more frequently presented a regression of maxLCBI4mm (27.6±0.1 vs. 61.5±0.1%, p=0.01). Multivariate analysis adjusting age, female and high-intensity statin use demonstrated change in ApoB as an independent factor associated with regression of maxLCBI4mm (OR=0.94, 95%CI=0.91-0.98, p=0.002). Conclusion In statin-treated T2DM patients with CAD, any reduction of ApoB levels was associated with a greater regression of NIRS-derived maxLCBI4mm. The current findings indicate a potential anti-atherosclerotic effect of lowering ApoB levels, which induces delipidation of diabetic coronary atheroma. ApoB may be an important therapeutic target to modulate lipidic plaque materials in T2DM patients receiving a statin.

Intravascular ICG-enhanced NIRF-IVUS imaging to assess progressive atherosclerotic lesions in excised human coronary arteries

Indocyanine green (ICG)-enhanced intravascular near-infrared fluorescence (NIRF) imaging enhances the information obtained with intravascular ultrasound (IVUS) by visualizing pathobiological characteristics of atherosclerotic plaques. To advance our understanding of this hybrid method, we aimed to assess the potential of NIRF-IVUS to identify different stages of atheroma progression by characterizing ICG uptake in human pathological specimens. After excision, 15 human coronary specimens from 13 adult patients were ICG-perfused and imaged with NIRF-IVUS. All specimens were then histopathologically and immunohistochemically assessed. NIRF-IVUS imaging revealed colocalization of ICG-deposition to plaque areas of lipid accumulation, endothelial disruption, neovascularization and inflammation. Moreover, ICG concentrations were significantly higher in advanced coronary artery disease stages (p < 0.05) and correlated significantly to plaque macrophage burden (r = 0.67). Current intravascular methods fail to detect plaque biology. Thus, we demonstrate how human coronary atheroma stage can be assessed based on pathobiological characteristics uniquely captured by ICG-enhanced intravascular NIRF.

Effect of Statins on Serial Coronary Atheroma Burdens: Pooled Analysis from Six Randomised Clinical Trials

Effect of Statins on Serial Coronary Atheroma Burdens: Pooled Analysis from Six Randomised Clinical Trials

Endogenous androgens, coronary atheroma and remodeling in women with suspected ischemic heart disease: A report from the Women's Ischemia Syndrome Evaluation (WISE) study

BackgroundWomen have smaller coronary size than men independent of body surface area. Female to male heart transplantation demonstrates coronary lumen enlargement. PurposeTo investigate relationships between endogenous androgens and coronary luminal size in women with suspected ischemic heart disease (IHD). MethodsWe analyzed 69 women with available androgen levels. ResultsGroup mean age was 54 ± 10 years with 64 % post-menopausal. Lumen cross-sectional area (CSA) and external elastic membrane (EEM) CSA positively correlated with free testosterone (FT) (r = 0.29, p = 0.049; r = 0.29, p = 0.01), respectively, and negatively correlated with SHBG (r = −0.26, p = 0.03; r = −0.29, p = 0.02), respectively. Atheroma CSA positively correlated with FT (r = 0.24. p = 0.05). These correlations became non-significant after adjusting for waist circumference. ConclusionsIn women with suspected ischemic heart disease, endogenous androgens, coronary atheroma and luminal size are related, and may be moderated by waist circumference.

Anthrometric dimensions and their impact on cardiovascular risk factors.

Central obesity is an important risk factor for cardiovascular disease. The abdominal subcutaneous adipose tissue thickness (ASATT) can be used to evaluate central obesity. The objective of this study was to compare ASATT with cardiovascular risk factors and other anthropometric parameters to show that ASATT can be a useful tool for the early assessment of heart disease risk. In this observational cross-sectional study, anthropometric measurements of 100 autopsied decedents, including waist circumference, hip circumference, waist/height and waist/hip ratio, aortic outlet and coronary artery atheroma plaque densities, heart weight, ventricular wall thickness, and ASATT, were assessed. The research data were evaluated using the Statistical Package for the Social Sciences for Windows 25.0. The average ASATT of the male group was 40.36 mm (SD: 11.00), and the average of female cases was 46.34 mm (SD: 18.12). There was no statistically significant difference between the sexes and both age groups in terms of the ASATT score (P > .05). There was a positive correlation between ASATT and waist circumference, hip circumference, and waist/height ratio in both sexes (P < .05). While ASATT was not related to atheroma density in the coronary arteries of men (P > .05), it was correlated with atheroma density in all 3 coronary arteries of women (P < .05). In the male group, the aortic inner surface atheroma density was positively correlated with ASATT (P < .05). In both sexes, there was a positive correlation (P < .05) between ASATT and heart weight; however, no such correlation was observed with right and left ventricular wall thickness (P > .05). ASATT is related to other anthropometric measurements, atherosclerosis of critical vessels, and heart weight, and can be used to scan the patient population for heart disease risk assessment with noninvasive methods.

Glucagon-like Peptide-1 analogues and delipidation of coronary atheroma in statin-treated type 2 diabetic patients with coronary artery disease: The prespecified sub-analysis of the OPTIMAL randomized clinical trial

Background and aimsRandomized clinical trials have demonstrated the ability of glucagon-like peptide-1 analogues (GLP-1RAs) to reduce atherosclerotic cardiovascular disease events in patients with type 2 diabetes (T2D). How GLP-1RAs modulate diabetic atherosclerosis remains to be determined yet. MethodsThe OPTIMAL study was a prospective randomized controlled study to compare the efficacy of 48-week continuous glucose monitoring- and HbA1c-guided glycemic control on near infrared spectroscopty (NIRS)/intravascular ultrasound (IVUS)-derived plaque measures in 94 statin-treated patients with T2D (jRCT1052180152, UMIN000036721). Of these, 78 patients with evaluable serial NIRS/IVUS images were analyzed to compare plaque measures between those treated with (n = 16) and without GLP-1RAs (n = 72). ResultsAll patients received a statin, and on-treatment LDL-C levels were similar between the groups (66.9 ± 11.6 vs. 68.1 ± 23.2 mg/dL, p = 0.84). Patients receiving GLP-1RAs demonstrated a greater reduction of HbA1c [-1.0 (-1.4 to −0.5) vs. −0.4 (-0.6 to −0.2)%, p = 0.02] and were less likely to demonstrate a glucose level >180 mg/dL [-7.5 (-14.9 to −0.1) vs. 1.1 (-2.0 - 4.2)%, p = 0.04], accompanied by a significant decrease in remnant cholesterol levels [-3.8 (-6.3 to −1.3) vs. −0.1 (-0.8 - 1.1)mg/dL, p = 0.008]. On NIRS/IVUS imaging analysis, the change in percent atheroma volume did not differ between the groups (−0.9 ± 0.25 vs. −0.2 ± 0.2%, p = 0.23). However, GLP-1RA treated patients demonstrated a greater frequency of maxLCBI4mm regression (85.6 ± 0.1 vs. 42.0 ± 0.6%, p = 0.01). Multivariate analysis demonstrated that the GLP-1RA use was independently associated with maxLCBI4mm regression (odds ratio = 4.41, 95%CI = 1.19–16.30, p = 0.02). ConclusionsIn statin-treated patients with T2D and CAD, GLP-1RAs produced favourable changes in lipidic plaque materials, consistent with its stabilization.

(015) Comparison of Penile Arterial Doppler-Ultrasound and Coronary Computed Tomography Angiography (CCTA) to Improve Cardiovascular Risk Assessment in Patients with Erectile Dysfunction

Abstract Introduction Erectile dysfunction (ED) has been shown to be an independent and early marker of future cardiovascular events, providing an important window of opportunity for cardiovascular preventive measures. However, there are several etiologies for ED (arterial, venous, hormonal, neurological, psychological), and earlier studies have not taken etiology into account when assessing cardiovascular risk. Arterial ED etiology share risk factors and pathophysiologic mechanisms with coronary and neurovascular diseases. Therefore, it can be assumed that patients with ED with arterial (atherosclerotic) etiology have a higher risk of future cardiovascular events than the general ED population. Objective To evaluate the predictive value of penile artery Doppler ultrasound (DUS) in cardiovascular risk assessment by comparing it with coronary atheroma screening by Coronary computed tomography angiography (CCTA) in patients with erectile dysfunction. Methods Men under 70 years of age, with ED and at least 1 cardiovascular risk factor (hypertension, dyslipidemia, diabetes, smoking, metabolic syndrome, obesity) were included. Patients with a primary cardiovascular event were excluded. Every patient had a penile DUS to assess penile arterial disease based on the maximum systolic velocity of the carvernous arteries after stimulation by intracavernous injection (A-Score), and a CCTA to assess coronary atheromatous arterial disease (CAD-RADS score). Results From October 2022 to June 2023, 72 consecutive patients were included. Mean age was 55 +/- 8.6 years. Mean IIEF5 score was 11 +/-5.3. N=34 (30%) were smokers, n=24 (33%) had hypertension, n=27 (37.5%) had diabetes, n=9 (11.1%) had obesity, n=10 (13.9%) had dyslipidemia. On penile artery DUS assessment n=62 (86%) patients had a positive A-Score. On CCTA, CAD-RADS scores were 0 in n=13 (18%) patients, 1 in n=18 (25%), 2 in n=19 (26%), 3 in n=17 (24%), and 4 in n=5 (7%) patients. We then analyzed the predictive value of A-Score as follows: 1. patients with coronary atheromatous plaques on CCTA (CAD-RADS ≥1, n=59), were significantly more likely to have a positive A-Score (n=56, 94.9%) than negative A-Score (n=13, 18%, p&amp;lt;.001, Chi2-test). The positive predictive value of the A-Score indicating penile arterial disease for the presence of coronary plaque, was 90.3%. 2. Patients with significant coronary stenosis (CAD-RADS ≥3, n=22) all patients n=22 (100%), had a positive A-Score and none a negative test (p=.026). The positive predictive value of the A-Score for the presence of significant coronary stenosis on CCTA was 100%. Conclusions The penile artery Doppler ultrasound A-Score has a good predictive value for coronary atheromatous artery disease in patients with erectile dysfunction, and allowed us to identify a sub-population at higher cardiovascular risk. When the A-Score is positive, the presence of coronary plaque is highly probable; when it is negative, the presence of significant coronary stenosis is highly unlikely. Disclosure No.

Cardiovascular Diseases and Adipokines: The Role of Visfatin in Coronary Atherosclerosis

Coronary artery disease (CAD) is a leading cause of cardiovascular disease-related mortality globally. Traditional risk indicators for CAD, such as age, gender, hypertension, and cholesterol levels, may not reliably predict the existence and severity of the disease in all individuals. Furthermore, these risk variables may not provide information regarding the long-term prognosis and survival of the patients with stable CAD. The limitations of present screening approaches suggest the need to develop novel prognostic biomarkers for the detection of coronary atherosclerosis (CA). This review focuses on the significance of adipokines in the pathophysiology of CA. The article discusses the role of various cytokines, focusing on visfatin in developing and progressing coronary atheroma and its potential to improve risk stratification, increase diagnostic accuracy, and guide therapy decisions. Clinical evidence supporting visfatin’s role as a diagnostic marker for CAD is already available, with elevated levels observed in patients with significant CA. However, the paper acknowledges certain limitations, such as the need for more extensive longitudinal studies to validate its potential use in clinical practice to improve early diagnosis and prognosis, ultimately enhancing strategies for preventing cardiovascular disease.

Single-cell profiling of CD11c+ B cells in atherosclerosis.

Circulating CD11c+ B cells, a novel subset of activated B cells, have been linked to autoimmunity and shown to expand with age. Atherosclerosis is an age-associated disease that involves innate and adaptive immune responses to modified self-antigens. Yet, the expression of CD11c on specific B-cell subtypes and its link to atherosclerosis are poorly understood. In this study, we characterized the frequency of CD11c+ B cells in tissues in mice with aging. We observed an age-associated increase in CD11c+ B cells in the spleen and bone marrow of ApoE-/- mice, and this was associated with an increase in aortic plaque. In addition, we also utilized single-cell multi-omics profiling of 60 human subjects undergoing advanced imaging for coronary artery disease (CAD) to subtype CD11c+ B cells and determine their frequency in subjects with high and low severity of CAD. Using unsupervised clustering, we identified four distinct clusters of CD11c+ B cells, which include CD27 and IgD double negative 2 (DN2), age-associated (ABC), CD11c+ unswitched memory (USWM), and activated Naïve (aNav) B cells. We observed an increase in the frequency of both ABC B cells and DN2 B cells in patients with high CAD severity. Pathway analysis further demonstrated augmentation of autophagy, IFNg signaling, and TLR signaling in DN2 cells in high-severity CAD patients. On the other hand, an increase in the negative regulator of BCR signaling through CD72 was found in ABC cells in low-severity CAD patients. Through investigating scRNAseq of atheroma, these DN2 cells were also found to infiltrate human coronary atheroma.

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

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

Characterization of lipidic coronary atheroma under control of low-density lipoprotein &amp;lt;1.8 mmol/l and lipoprotein (a) &amp;lt;50 mg/dl in patients with coronary artery disease

Abstract Background Lp(a) has been considered as a potential therapeutic target associated with atherosclerosis. In particular, Lp(a) ≧50 mg/dL has been shown to predict an elevated cardiovascular risk even under lowering LDL-C level, indicating that lowering of both LDL-C and Lp(a) may be more beneficial to halt atherogenesis. However, atherosclerotic features with favorable control of these lipid targets have not been fully characterized yet. The REASSURE-NIRS registry (NCT04864171) is an on-going multi-center registry which enrolls CAD patients receiving near-infrared spectroscopy (NIRS)/IVUS-guided PCI in Japan. Given that NIRS enables to quantitatively evaluate lipidic plaque materials, this registry provides an opportunity to investigate lipidic plaque features in association with LDL-C and Lp(a) levels. Objectives The aim of this study was to elucidate NIRS-derived characteristics of coronary atheroma in patients with CAD who exhibited both LDL-C&amp;lt;1.8 mmol/L and Lp(a) &amp;lt;50 mg/dL. Methods From the REASSURE-NIRS registry (n=1013), we investigated 549 culprit lesions in 498 patients with measurement of both LDL-C and Lp(a) levels at the index of PCI. Maximum 4-mm lipid core burden index (max LCBI4mm) at culprit lesions were measured with NIRS imaging prior to PCI. Study subjects were stratified into 4 groups according to LDL-C and Lp(a) levels: LDL-C&amp;lt;1.8mmol/L and Lp(a)&amp;lt;50mg/dL, LDL-C≧1.8mmol/ and Lp(a)&amp;lt;50mg/dL, LDL-C&amp;lt;1.8mmol/L and Lp(a)≧50mg/dL, LDL-C≧1.8mmol/L and Lp(a)≧50mg/dL. Clinical characteristics and max LCBI4mm were compared in 4 groups. Results In the current study, 30.6% of patients was ACS. Under the use of lipid-lowering therapies (statin: 68.4% and high-intensity statin: 26.0%), 33.1% of study population exhibited both LDL-C&amp;lt;1.8mmol/L and Lp(a)&amp;lt;50mg/dL. Patients with LDL-C&amp;lt;1.8mmol/L and Lp(a)&amp;lt;50mg/dL were more likely to be male (p=0.002) and smoker (p=0.002) and have a history of previous MI (p&amp;lt;0.001). As expected, statin was more frequently used in those with both LDL-C&amp;lt;1.8mmol/L and Lp(a)&amp;lt;50mg/dL (p&amp;lt;0.001). On NIRS imaging analysis, patients with low LDL-C&amp;lt;1.8mmol/L and Lp(a)&amp;lt;50mg/dL were associated with significantly lower max LCBI4mm (Figure). Of note, even in patients with LDL-C&amp;lt;1.8mmol/L, max LCBI4mm was lower in those achieving Lp(a) &amp;lt;50 mg/dL compared to those with Lp(a) ≧50 mg/dL (p=0.001). Multivariate analysis adjusting for ACS, LDL-C levels and statin use, Lp(a) levels revealed emerged as independent predictor of maxLCBI4mm (β=1.0, 95%CI: 0.06 to 2.04, p=0.04). Conclusion Patients with LDL-C&amp;lt;1.8mmol/L and Lp(a)&amp;lt;50mg/dL more likely exhibited a smaller amount of lipidic plaque materials on NIRS imaging. Our findings support that lowering both LDL-C and Lp(a) may be more beneficial to modulate lipidic plaque component, which ultimately results in the further reduction of ASCVD risks.Comparison of clinical characteristics

Changes in cardiac electrical biomarker with hyperaemic stress: an experimental perspective

Abstract Background "Cardiac electrical biomarker" (CEB) is a numerical index measured by the Vectraplex ECG (vECG) System with Vectraplex AMI software that measures changes in the cardiac electrical field vectors from dipolar to multipolar during myocardial ischemia. CEB performs well in detecting NSTEMI and STEMI against physician adjudicated diagnosis. Purpose To assess changes in CEB during adenosine stress induced ischaemia. Method Thirty-three patients, in the VECTRA-PCI trial, with normal surface ECG (sECG) had CEB measured before (CEB0), at maximal hyperaemia (CEBh)) and 1-(CEB1), 2-(CEB2) and 3-(CEB3) hours after standard fractional flow reserve (FFR) assessment using intravenous adenosine. vECGs were adjudicated for quality by 2 blinded observers. vECGs with artefacts and arrhythmias were discarded and CEBs from best traces were analysed. Forty-nine individuals with non-cardiac chest pain, without past medical history or risk factors for CAD, on no medications, normal ECGs, normal blood profile acted as controls. CEBs (median, IQR) were compared using appropriate tests. Results FFR was normal (&amp;gt;/=0.80) (nFFR) in 25 and ischaemic (&amp;lt;0.80) (iFFR) in 8 patients. CEB0 in nFFR and iFFR groups were similar to each other (p=0.785) (Fig 1) and to controls (30.0; IQR 17.0-44.0, vs nFFR: p=0.057, vs iFFR: p=0.241). Compared to CEB0, CEBh was higher in nFFR (p=0.014) (Fig 1A) and iFFR (p=0.016) groups (Fig 1B). CEBh in iFFR (126.0; 109.5-216.0) higher than nFFR (44.0; 27.8-104.8), (p=0.039). In nFFR group, CEB1, 2 and 3, though numerically lower, were statistically similar to CEBh and CEB0 (Fig 1A) suggesting quick recovery. In iFFR group CEB1 was similar to and CEB2 and 3 were lower than CEBh (Fig 1B) suggesting a slower recovery of CEB. Both CEBh and change from CEB0 to CEBh (δCEB0-h), but not CEB0, predicted ischaemic FFR with similar accuracy (p=0.570) (Fig 2). CEBh &amp;gt;96 and δCEB0-h &amp;gt;28 had similar sensitivity of 87.5% with specificity of 68% and 80% respectively. Conclusion Obstructive coronary atheroma is associated with higher CEB than non-obstructive atheroma under hyperaemic stress. Both CEBh and δCEB0-h accurately predict ischaemic FFR with higher specificity of δCEB0-h. This is the first study to measure CEB changes with hyperaemic stress in patients with coronary artery disease and could have potential for wider clinical application. Figure 1. Changes in the CEB during and after hyperaemic stress in patients with normal (A) and ischaemic (B) FFR. Figure 2. Area under the ROC curve to determine the diagnostic accuracy of pre-procedural CEB, hyperaemic CEB and change in CEB from baseline to hyperaemia in determining ischaemic FFR.Fig 1. Changes in CEB with stress.Fig 2. CEB for ischaemic FFR

Abstract 15154: Therapeutic Effect of Optimal Medication on Biochemical Plaque Composition in Patients With Coronary Artery Disease as Serially Assessed by Intravascular Multi-Targeted Fluorescence Lifetime Imaging Fully Integrated With OCT

Introduction: Fluorescence lifetime imaging (FLIm) is an emerging technique that can visualize detailed molecular properties of atherosclerosis. We conducted an in vivo serial molecular characterization of human coronary plaques using a fully-integrated, dual-modal, intravascular optical coherence tomography-FLIm (OCT-FLIm) system to explore the natural history of biochemical plaque composition. Methods: We prospectively enrolled patients with significant coronary artery disease those who underwent 6-month serial OCT-FLIm assessment for non-culprit/non-target lesions. A non-culprit/non-target lesion was defined as medically-treated angiographic mild-to-moderate stenosis diagnosed at index procedure. Biochemical plaque compositions were categorized by FLIm-derived parameters using a dedicated machine learning classifier. Each lesion was quantitatively assessed for the pre-specified plaque compositions and compared with the serial images. Results: Total 53 non-culprit/non-target lesions from 30 patients were enrolled. Angiography- and OCT-defined lesion severity showed no significant difference over the follow-up (p&gt;0.05). Intriguingly, while the macrophage signal intensity decreased after 6 months (p=0.034), FLIm-based quantitative assessment revealed a worsened plaque compositional response by increased loose fibrous tissue (p=0.004) and decreased normal/fibrous tissue burden (p&lt;0.001). These temporal changes in individual plaque components correlated well with the achieved LDL-cholesterol level at 6-month (p&lt;0.05), whereas no correlation was found with hs-CRP (p&gt;0.05). Conclusion: From this comprehensive serial assessment of human coronary atheroma by intravascular OCT-FLIm, optimal medical therapy alone was insufficient to effectively stabilize plaque composition, and additional therapeutic strategy should be explored to alter the natural course of atherosclerosis from a molecular perspective.

France LILI (LIthopLastie Intracoronaire)

BackgroundIntravascular lithotripsy (IVL) is a novel and appealing device for the preparation of coronary calcified lesions before stenting. This technology has received CE mark and FDA approval, according to the data of the CAD studies. However, these clinical trials show numerous limits as the exclusion of a subset of lesions (Left main, CTO, in stent restenosis …) and patients’ over-selection. In this view, applications of IVL results in daily practice are debatable according to the lack of evidence in unselected patients. MethodsFRANCE-LILI is a prospective national academic registry evaluating the safety and effectiveness of adjunctive intravascular lithotripsy in coronary angioplasty in an all-comers patient population in France. The registry is registered with the ClinicalTrials.gov database (NCT05113407) and managed by the French Coronary Atheroma and Interventional Cardiology Group (GACI) of the French Society of Cardiology (FSC).France LILI will prospectively enroll 500 subjects. The primary endpoint is target vessel failure (TVF) at one year, defined as a composite of cardiac death, myocardial infarction (MI) according to the Academic Research Consortium-2 (ARC-2) definition (except for an MI clearly attributed to a non-target vessel) and revascularization of the target vessel. All endpoints are evaluated and confirmed by an independent adjudication committee. ConclusionThis national prospective academic registry will provide fruitful data on IVL in an unselected population of complex coronary lesions.

Associations of High-Density Lipoprotein Functionality with Coronary Plaque Characteristics in Diabetic Patients with Coronary Artery Disease: Integrated Backscatter Intravascular Ultrasound Analysis.

High-density lipoprotein (HDL) functionality has been reported to be associated with coronary artery disease (CAD). However, little is known about the impact of HDL functionality on coronary atherosclerosis. Thirty-eight type 2 diabetic patients with CAD who underwent percutaneous coronary intervention were examined. Coronary atheroma burden and plaque composition of the culprit lesions were assessed using conventional gray-scale and integrated backscatter intravascular ultrasound. HDL-mediated cholesterol efflux capacity (HDL-CEC) and HDL antioxidant capacity, estimated as HDL inflammatory index (HII), were examined. The associations between HDL functionality and coronary plaques were analyzed using multivariate data analysis, including principal components analysis and orthogonal partial least squares (OPLS) models. Percent atheroma volume was correlated with HDL-CEC (r = 0.34, p = 0.04) but not with HII (p = 0.65). The OPLS model demonstrated that the percentage lipid volume was significantly associated with HDL functionality [coefficient (95% confidence interval); HDL-CEC: -0.26 (-0.49, -0.04); HII: 0.34 (0.08, 2.60), respectively]. HII exhibited the highest variable importance in projection score, indicating the greatest contribution. HDL functionality was associated with coronary plaque composition, a key component of plaque vulnerability. Our findings highlight the potential importance of HDL functionality for coronary plaque stabilization.

Coronary artery disease grading by cardiac CT for predicting outcome in patients with stable angina

BackgroundThe coronary atheroma burden drives major adverse cardiovascular events (MACE) in patients with suspected coronary heart disease (CHD). However, a consensus on how to grade disease burden for effective risk stratification is lacking. The purpose of this study was to compare the effectiveness of common CHD grading tools to risk stratify symptomatic patients. MethodsWe analyzed the 5-year outcome of 381 prospectively enrolled patients in the CORE320 international, multicenter study using baseline clinical and cardiac computer-tomography (CT) imaging characteristics, including coronary artery calcium score (CACS), percent atheroma volume, “high-risk” plaque, disease severity grading using the CAD-RADS, and two simplified CAD staging systems. We applied Cox proportional hazard models and area under the curve (AUC) analysis to predict MACE or hard MACE, defined as death, myocardial infarction, or stroke. Analyses were stratified by a history of CHD. Additional forward selection analysis was performed to evaluate incremental value of metrics. ResultsClinical characteristics were the strongest predictors of MACE in the overall cohort. In patients without history of CHD, CACS remained the only independent predictor of MACE yielding an AUC of 73 (CI 67–79) vs. 64 (CI 57–70) for clinical characteristics. Noncalcified plaque volume did not add prognostic value. Simple CHD grading schemes yielded similar risk stratification as the CAD-RADS classification. Forward selection analysis confirmed prominent role of CACS and revealed usefulness of functional testing in subgroup with known CHD. ConclusionIn patients referred for invasive angiography, a history of CHD was the strongest predictor of MACE. In patients without history of CHD, a coronary calcium score yielded at least equal risk stratification vs. more complex CHD grading.

Prevalence of Coronary Atheroma and 2-year Outcomes in Patients Presenting with Chest Pain at Intermediate Risk for Coronary Artery Disease

Prevalence of Coronary Atheroma and 2-year Outcomes in Patients Presenting with Chest Pain at Intermediate Risk for Coronary Artery Disease

Characterization of plaque phenotypes exhibiting an elevated pericoronary adipose tissue attenuation: insights from the REASSURE-NIRS registry.

Inflammation has been considered to promote atheroma instability. Coronary computed tomography angiography (CCTA) visualizes pericoronary adipose tissue (PCAT) attenuation, which reflects coronary artery inflammation. While PCAT attenuation has been reported to predict future coronary events, plaque phenotypes exhibiting high PCAT attenuation remains to be fully elucidated. The current study aims to characterize coronary atheroma with a greater vascular inflammation. We retrospectively analyzed culprit lesions in 69 CAD patients receiving PCI from the REASSURE-NIRS registry (NCT04864171). Culprit lesions were evaluated by both CCTA and near-infrared spectroscopy/intravascular ultrasound (NIRS/IVUS) imaging prior to PCI. PCAT attenuation at proximal RCA (PCATRCA) and NIRS/IVUS-derived plaque measures were compared in patients with PCATRCA attenuation ≥ and < -78.3 HU (median). Lesions with PCATRCA attenuation ≥ -78.3 HU exhibited a greater frequency of maxLCBI4mm ≥ 400 (66% vs. 26%, p < 0.01), plaque burden ≥ 70% (94% vs. 74%, p = 0.02) and spotty calcification (49% vs. 6%, p < 0.01). Whereas positive remodeling (63% vs. 41%, p = 0.07) did not differ between two groups. On multivariable analysis, maxLCBI4mm ≥ 400 (OR = 4.07; 95%CI 1.12-14.74, p = 0.03), plaque burden ≥ 70% (OR = 7.87; 95%CI 1.01-61.26, p = 0.04), and spotty calcification (OR = 14.33; 95%CI 2.37-86.73, p < 0.01) independently predicted high PCATRCA attenuation. Of note, while the presence of only one plaque feature did not necessarily elevate PCATRCA attenuation (p = 0.22), lesions harboring two or more features were significantly associated with higher PCATRCA attenuation. More vulnerable plaque phenotypes were observed in patients with high PCATRCA attenuation. Our findings suggest PCATRCA attenuation as the presence of profound disease substrate, which potentially benefits from anti-inflammatory agents.