Spotty Calcification Research Articles

Coronary plaque vulnerability in statin-treated patients with elevated LDL-C and hs-CRP: optical coherence tomography study.

There have been no previous attempts to assess coronary plaque morphology in statin-treated patients with combined residual cholesterol and inflammatory risk. The aim of this study was to characterize the morphology using optical coherence tomography (OCT) and to investigate the underlying molecular mechanisms. Two hundred seventy statin-treated patients with stable coronary artery disease who underwent OCT imaging prior to elective percutaneous coronary intervention were included in this single-center retrospective analysis. Subjects were stratified into four groups based on low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP) levels using 70mg/dl and 2mg/L as cut-offs, respectively. OCT images of the target lesions were assessed. For a subset of patients, peripheral blood mononuclear cells (PBMC) were isolated, and gene expression was characterized using microarray analysis. Patients with high LDL-C and high hs-CRP demonstrated a higher frequency of lipid-rich plaques (LRP) (91%, P = 0.03) by OCT. LRPs in these patients had a greater maximal lipid arc (186.6 ± 92.5°, P = 0.047). In addition, plaques from patients who did not achieve dual-target were less frequently calcified (P = 0.003). If calcification was present, it was characterized by a lower maximal arc (P = 0.016) and shorter length (P = 0.025). PBMC gene expression analysis demonstrated functional enrichment of toll-like receptors (TLRs) 1-9 to be associated with high LDL-C and hs-CRP. Obstructive coronary lesions in patients on statin therapy with combined residual cholesterol and inflammatory risk demonstrated a higher prevalence of LRP with greater maximal lipid arcs and more frequent spotty calcifications. PBMC from these patients revealed functional enrichment of TLR 1-9.

High pericoronary adipose tissue attenuation on computed tomography angiography predicts cardiovascular events in patients with type 2 diabetes mellitus: post-hoc analysis from a prospective cohort study

BackgroundPericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) is a non-invasive biomarker for pericoronary inflammation. We aimed to investigate the prognostic value of PCAT attenuation in patients with type 2 diabetes mellitus (T2DM).MethodsWe included 333 T2DM patients (mean age, 66 years; male patients, 211; mean body mass index, 25 kg/m2) who underwent clinically indicated coronary CTA and examined their CT findings, coronary artery calcium score, pericardial fat volume, stenosis (> 50% luminal narrowing), high-risk plaque features of low-attenuation plaque and/or positive remodelling and/or spotty calcification, and PCAT attenuation. We assessed PCAT attenuation in Hounsfield units (HU) of proximal 40-mm segments of the left anterior descending artery (LAD) and right coronary artery (RCA). Cardiovascular events were defined as cardiac death, hospitalisation for acute coronary syndrome, late coronary revascularisation, and hospitalisation for heart failure.ResultsDuring a median follow-up of 4.0 years, we observed 31 cardiovascular events. LAD-PCAT attenuation was significantly higher in patients with cardiovascular events than in those without (− 68.5 ± 6.5 HU vs − 70.8 ± 6.1 HU, p = 0.045), whereas RCA-PCAT attenuation was not (p = 0.089). High LAD-PCAT attenuation (> − 70.7 HU; median value) was significantly associated with cardiovascular events in a model that included adverse CTA findings, such as significant stenosis and/or high-risk plaque (hazard ratio; 2.69, 95% confidence interval; 1.17–0.20, p = 0.020). After adding LAD-PCAT attenuation to the adverse CTA findings, the C-statistic and global chi-square values increased significantly from 0.65 to 0.70 (p = 0.037) and 10.9–15.0 (p = 0.043), respectively.ConclusionsIn T2DM patients undergoing clinically indicated coronary CTA, high LAD-PCAT attenuation could significantly predict cardiovascular events. This suggests that assessing LAD-PCAT attenuation can help physicians identify high-risk T2DM patients.

Detection of Vulnerable Coronary Plaques Using Invasive and Non-Invasive Imaging Modalities.

Acute coronary syndrome (ACS) mostly arises from so-called vulnerable coronary plaques, particularly prone for rupture. Vulnerable plaques comprise a specific type of plaque, called the thin-cap fibroatheroma (TFCA). A TCFA is characterized by a large lipid-rich necrotic core, a thin fibrous cap, inflammation, neovascularization, intraplaque hemorrhage, microcalcifications or spotty calcifications, and positive remodeling. Vulnerable plaques are often not visible during coronary angiography. However, different plaque features can be visualized with the use of intracoronary imaging techniques, such as intravascular ultrasound (IVUS), potentially with the addition of near-infrared spectroscopy (NIRS), or optical coherence tomography (OCT). Non-invasive imaging techniques, such as computed tomography coronary angiography (CTCA), cardiovascular magnetic resonance (CMR) imaging, and nuclear imaging, can be used as an alternative for these invasive imaging techniques. These invasive and non-invasive imaging modalities can be implemented for screening to guide primary or secondary prevention therapies, leading to a more patient-tailored diagnostic and treatment strategy. Systemic pharmaceutical treatment with lipid-lowering or anti-inflammatory medication leads to plaque stabilization and reduction of cardiovascular events. Additionally, ongoing studies are investigating whether modification of vulnerable plaque features with local invasive treatment options leads to plaque stabilization and subsequent cardiovascular risk reduction.

Effect of long-term intensive cholesterol control on the plaque progression in elderly based on CTA cohort study.

To investigate the long-term effects of intensive LDL cholesterol-lowering treatments on lumen stenosis severity, plaque calcification, spotty calcifications, percent calcified plaque volume (PCPV), and Agatston coronary artery calcium score (CACS) based on coronary computed tomography angiography (CCTA) in elderly patients. A total of 240 patients over 60 years old (comprising 754 lesions) who underwent serial CCTA were retrospectively enrolled in this 5-year cohort study. Patients were divided into three groups: an intensive lipid-lowering group, a lipid-lowering group, and a control group. The stenosis severity, plaque volume (PV), plaque composition, PCPV, and high-risk plaque (HRP) presence were quantitatively analyzed. The CACS was calculated at baseline and follow-up. All patients were male with an average age of 66.8 ± 5.8 years old. Over time, increases in the percentages of obstructive coronary lesions (p < 0.001) were observed. Compared with those at baseline, the percentage of obstructive lesions remained unchanged (p = 0.077), and the percentage of spotty calcifications significantly decreased (p < 0.05) at the follow-up CCTA scan in the intensive lipid-lowering group. Patients in the intensive lipid-lowering group demonstrated a higher progression in calcified PV, CACS, and PCPV (all p < 0.05), and a significantly greater attenuation in fibrous-fatty and lipid-rich PV (all p < 0.05) than patients in other groups. The PV and contents increased gradually with time in all groups. Intensive LDL-C lowering was associated with slower progression of stenosis severity and reduction of high-risk plaque features, with increased plaque calcification and higher progression in PCPV. Comprehensive serial plaque evaluations by CCTAs may contribute to further refinement of risk stratification and reasonable lipid-lowering treatment in elderly patients. • Intensive LDL-C lowering increased coronary calcification and percent calcified plaque volume progression. • Comprehensive serial plaque evaluations by serial CCTAs may help to refine risk stratification.

Plaque microstructures during metformin therapy in type 2 diabetic subjects with coronary artery disease: optical coherence tomography analysis.

While metformin is recommended as a first-line cardioprotective therapy for type 2 diabetic patients, whether it exerts direct effects on atherosclerotic plaque remains uncertain. The current study characterized coronary plaque microstructures in type 2 diabetic patients who received metformin. We retrospectively analyzed 409 non-culprit lipid plaques in 313 type 2 diabetic patients with coronary artery disease (CAD) by using frequency-domain optical coherence tomography (FD-OCT) imaging. FD-OCT derived plaque microstructures were compared in patients stratified according to metformin use. A proportion of 38.6% of study subjects received metformin. Patients receiving metformin more likely exhibited a history of hypertension (79.3% vs. 67.1%, P=0.03) and metabolic syndrome (52.8% vs. 36.4%, P=0.01). On FD-OCT imaging, the prevalence of lipid plaque was lower in the metformin group (66.2% vs. 77.9%, P=0.03). Furthermore, the metformin group demonstrated plaques with a smaller lipid arc (median: 168.7° vs. 208.5°, P=0.008), shorter longitudinal length (media: 5.1 vs. 9.1 mm, P=0.04), and a lower frequency of cholesterol crystal (3.9% vs. 18.2%, P=0.01) and spotty calcification (3.9% vs. 34.8%, P=0.008). These differences remained significant after adjusting for clinical characteristics and glycemic control. However, in patients who received insulin, the favourable effect of metformin on lipid arc was not observed (insulin user: P=0.87; insulin non-user: P=0.009; P value for interaction between two groups, P=0.02). Metformin use was associated with a lower prevalence of vulnerable plaque features in type 2 diabetic patients with CAD, especially insulin non-user. These findings suggest the potential of metformin to exert direct plaque stabilization effects in type 2 diabetic subjects.

Coronary Computed Tomography Angiographic Predictors of Non-culprit Territory Unrecognized Myocardial Infarction Assessed by Cardiac Magnetic Resonance in Non-ST-elevation Acute Coronary Syndrome.

ObjectivesThis study sought to assess the predictors of coronary computed tomography angiographic findings for non-infarct-related (non-IR) territory unrecognized myocardial infarction (UMI) in patients with a first episode of non-ST-elevation acute coronary syndrome (NSTE-ACS).BackgroundUMI detected by cardiac magnetic resonance imaging (CMR) is associated with adverse outcomes in patients with both acute coronary syndrome and chronic coronary syndrome. However, the association between the presence of UMI and coronary computed tomography angiographic (CCTA) findings remains unknown.MethodsWe investigated 158 patients with a first clinical episode of NSTE-ACS, who underwent pre-PCI 320-slice CCTA and uncomplicated urgent percutaneous coronary intervention (PCI) within 48 h of admission. In these patients, post-PCI CMR was performed within 30 days from urgent PCI and before non-IR lesion staged PCI. UMI was assessed using late gadolinium enhancement (LGE)-CMR by identifying regions of hyperenhancement with an ischemic distribution pattern in non-IR territories (non-IR UMI). CCTA analysis included qualitative and quantitative assessments of the culprit segment, Agatston score, mean peri-coronary fat attenuation index (FAI), epicardial fat volume (EFV) and epicardial fat attenuation (EFA).ResultsNon-IR UMI was detected in 30 vessel territories (9.7%, 30/308 vessels) of 28 patients (17.7%, 28/158 patients). The presence of low-attenuation plaque, spotty calcification, napkin ring sign, and positive remodeling was not significantly different between vessels with and without subtended non-IR UMI. Agatston score >30.0 (OR: 8.39, 95% confidence interval (CI): 2.17 to 32.45, p = 0.002), mean FAI >-64.3 (OR: 3.23, 95% CI: 1.34 to 7.81, p = 0.009), and stenosis severity (OR: 1.04, 95% CI: 1.02 to 1.06, p < 0.001) were independently associated with non-IR UMI. Neither EFV (p = 0.340) nor EFA (p = 0.700) was associated with non-IR UMI.ConclusionThe prevalence of non-IR UMI was 17.7 % in patients with first NSTE-ACS presentation. Agatston score, mean FAI, and coronary stenosis severity were independent CCTA predictors of the presence of non-IR UMI. The integrated CCTA assessment may help identify the presence of non-IR UMI before urgent PCI.

Clinical Course of Optical Coherence Tomography-Detected Lipid-Rich Coronary Plaque After Optimal Medical Therapy

Background: The aim of this study was to evaluate optical coherence tomography (OCT)-detected lipid-rich coronary plaques (LRCPs) with coronary computed tomography angiography (CCTA) 10 months after optimal medical therapy (OMT). Methods and Results: Baseline OCT detected 28 LRCPs in non-culprit lesions. High-risk plaque features (HRPFs), such as positive remodeling, very low attenuation plaques, napkin-ring sign, and spotty calcification, were observed in 67.9%, 67.9%, 21.4%, and 64.3% of LRCPs, respectively, at the 10-month follow-up CCTA. Lesions with ≥3 HRPFs were defined as high-risk LRCPs (n=12); the remaining were defined as low-risk LRCPs (n=16). The maximum lipid arc on baseline OCT was larger in high- than low-risk LRCPs (221±62° vs. 179±44°, respectively; P=0.04). Receiver operating characteristic curve analysis indicated that a maximum lipid arc >154° on baseline OCT was the optimal cut-off value to predict high-risk LRCPs 10 months after OMT. Patients with high-risk LRCPs had worse clinical outcomes, defined as a composite of cardiac death, target lesion-related myocardial infarction, and target lesion-related revascularization, during follow-up than those with low-risk LRCPs (33.3% vs. 0%; P=0.01). Conclusions: A high-risk LRCP at follow-up CCTA was correlated with a larger maximum lipid arc on baseline OCT. Further aggressive treatment for patients with large LRCPs may reduce vulnerable plaque features and prevent future cardiac events.

Comparison of symptomatic vertebrobasilar plaques between patients with and without Diabetes Mellitus using computed tomographic angiography and vessel wall magnetic resonance imaging.

ObjectivesDiabetes mellitus is significantly associated with posterior circulation ischemic stroke. We aimed to compare the characteristics of vertebrobasilar plaques in symptomatic patients with and without diabetes using high-resolution vessel wall magnetic resonance imaging and computed tomographic angiography.MethodsFrom April 2017 to May 2021, cases from patients with transient ischemic attack or stroke in the posterior circulation territory who underwent high-resolution vessel wall magnetic resonance imaging and computed tomographic angiography were reviewed. Characteristics of culprit vertebrobasilar plaques were compared between patients with and without diabetes. Multivariate regression analysis was performed to assess the correlation between culprit plaque characteristics and diabetes.ResultsA total of 148 patients were included and 75 patients were diagnosed with diabetes mellitus. Patients with diabetes had more intraplaque hemorrhage, calcification, spotty calcification presence, and higher calcification volume (all p < 0.05) compared with those without diabetes. Multivariate analysis demonstrated differences in the presence of intraplaque hemorrhage (p = 0.045) and number of spotty calcifications (p = 0.047) were statistically significant after adjusting for baseline characteristics.ConclusionsSymptomatic patients with diabetes have a higher incidence of intraplaque hemorrhage and larger calcification burden than those without diabetes, indicating the association of diabetes with more advanced plaque features in the posterior circulation.

The Potential Role of Cardiac CT in Patients with Acute Coronary Syndrome

급성 관상동맥 증후군은 관상동맥 경화반의 갑작스러운 파열과 관련된 3가지 유형의 관상동맥 질환을 의미하며 임상적으로는 ST 분절 상승 심근경색에서 비 ST 분절 상승 심근경색 또는 불안정성 협심증 등으로 표현된다. 심장 CT의 기술 발전을 통해 심장 CT는 관상동맥 내 죽상동맥경화반의 정량화 및 특성을 평가할 수 있게 되었으며, 현재까지 낮은 감쇠의 경화반, 냅킨 반지 표시, 양성 리모델링, 점상 석회화 및 증가된 혈관 주변 지방 감쇠가 심장 CT에서 경화반 파열을 의미하는 것으로 알려져 있다. 따라서 심장 CT는 관상동맥의 혈관협착정도를 진단하는 것을 넘어 급성 관상동맥 증후군을 진단하는데도 많은 기여를 하고 있다.

103 Coronary plaque healing and diabetes: insights from optical coherence tomography imaging

Abstract Aims Atherosclerotic plaque healing is a dynamic process developing after plaque rupture or erosion, which aims to prevent lasting occlusive thrombus formation and to promote plaque repair. We hypothesized that diabetes mellitus, one of the major conventional cardiovascular risk factors, may influence the healing capacity after plaque destabilization. Methods and results In this single-centre observational cohort study, patients with acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) who underwent optical coherence tomography (OCT) imaging at Fondazione Policlinico A. Gemelli–IRCCS, Rome, were included. Patients were divided into two groups (i.e. diabetes vs. no diabetes), and stratified based on diabetes medications (i.e. insulin, vs. oral antidiabetic drugs). OCT analysis of non-culprit coronary segments was performed. 105 patients were included (44 diabetes, 61 no diabetes). Prevalence of HCPs was not significantly different between patients with and without diabetes (3.6% vs. 3.8%, P = 0.854). However, patients with diabetes on insulin showed a lower prevalence of HCPs both at patient-based (7.1% vs. 26.4%, P = 0.116) and at segment-based analysis (1.2% vs. 4.2%, P = 0.020). When comparing HbA1c levels based on the presence or absence of healed plaque at the non-culprit lesions, patients with healed plaque showed significantly lower levels of HbA1c compared to patients without healed plaques (43.5 ± 12.1% vs. 61.2 ± 10.4%, P &amp;lt; 0.001). At segment-based analysis, normal vessel structure, pathological intimal thickening (PIT), and spotty calcifications were significantly less prevalent in diabetic patients (2.1% vs. 5.1%, P = 0.001; 7.2% vs. 9.5%, P = 0.05; 9.9% vs. 13.6%, P = 0.02, respectively), whereas neovascularization was significantly higher (19.2% vs. 15.6%, P = 0.035). Conclusions Patients with diabetes have a distinct coronary non-culprit plaque phenotype. Healing capacity may be impaired in patients with advanced diabetes on insulin therapy and in those with a suboptimal control of the disease. Further prospective, larger scale studies are warranted to confirm these findings.

The association between intravascular ultrasound-derived echo-attenuation and quantitative flow ratio in intermediate coronary lesions.

The clinical relevance of moderate coronary stenosis is determined by its morphological characteristics and physiological significance. We investigated the relationship between high-risk plaque characteristics detected by intravascular ultrasound and functional significance assessed with quantitative flow ratio (QFR) in intermediate coronary lesions. QFR was retrospectively analyzed in 352 intermediate lesions from 330 patients undergoing intravascular ultrasound examination. The functional significance was defined as QFR ≤0.8. High-risk plaque morphologies including plaque rupture, echo-lucent, echo-attenuation, and spotty calcification were identified, and attenuation indices including maximum angle, attenuation length, and superficial attenuation were determined. Clinically relevant echo-attenuation was defined as an attenuation with a minimum lumen area ≤4.0 mm2 and plaque burden ≥70%. The prevalence of echo-attenuation was higher (63.0% vs. 37.6%, P=0.001) and attenuation length was longer (12.8±10.3 vs. 8.0±5.8 mm, P=0.015) in lesions with QFR ≤0.8 compared to those with QFR >0.8, associated with a higher rate of clinically relevant echo-attenuation (35.2% vs. 10.4%, P<0.001). On multivariable analysis, the presence of echo-attenuation was an independent predictor of QFR ≤0.8 [odds ratio (OR) 3.162, 95% confidence interval (CI): 1.263-7.917, P=0.014], whereas attenuation length was weakly correlated with QFR value (β=-0.185, B=-0.002, 95% CI: -0.004 to -0.001, P=0.001). Receiver-operating characteristic curve analysis revealed that the best cutoff of QFR in predicting clinically relevant echo-attenuation was 0.82 [area under the curve (AUC) =0.696, 95% CI: 0.616-0.775, P<0.001]. The presence of intravascular ultrasound-derived echo-attenuation confers an increased risk of QFR-defined functional significance in intermediate coronary lesions. Coronary artery disease; intermediate coronary lesion; quantitative flow ratio (QFR); intravascular ultrasound (IVUS); echo-attenuation.

Abstract 12629: Intravascular Dual Targeted NIRF Molecular Imaging Integrated With OCT for Calcifying Inflammatory Activity in the Plaque

Background/Objectives: Spotty calcification linked with macrophage activity is a major target for high-risk plaque but the biological interconncetion remains questionable. To address this issue, we newly developed intravascular multimodal imaging strategy by fully integration of OCT with dual-targeted near-infrared fluorescence (NIRF) molecular imaging using customized osteogenic activity and macrophage targetable probes. Methods/Results: We newly integrated intravascular OCT structural imaging with dual-targeted NIRF imaging. Scale-up novel NIRF emitting probe targeting osteogenic activity was fabricated by chemically coupling alendronate ligand and Cy5.5 to the ends of azide-PEG-NHS ester (Al-Cy5.5). Based on biodistribution, OCT/dual-NIRF in vivo imaging of rabbit aortoiliac atheroma was acquired 72 hrs after intravenous injection of Al-Cy5.5 (5.0 mg/kg) and macrophage mannose receptor targeted Cy7-emitting probe (7.5 mg/kg). NIRF signals of Cy5.5 and Cy7 were highly enhanced in spotty calcification and inflammatory sites of the plaque, respectively (Figure) (p&lt;0.01). Fluorescence microscopy and immunostainings from the corresponding sections well corroborated the in vivo findings. Intriguingly, an interconnection of osteogenic activity (TRAP stain) with macrophages was more prominent in superficial spotty calcification rather than outer dense calcification (Figure) (p&lt;0.01). Conclusions: Our intravascular OCT/dual-NIRF imaging was feasible to simultaneously image osteogenic activity and macrophages in the coronary-sized atheroma. This novel imaging strategy is expected to expand the understanding for the biological behavior of calcifying inflamed activity in the high-risk plaques existing on cap microcalcification.

The associations between coronary artery disease, and non-alcoholic fatty liver disease by computed tomography

BackgroundNon-alcoholic fatty liver disease (NAFLD) is increasing in recognition as a hepatic condition that is unrelated to significant alcoholic consumption, but has rather, been suggested to constitute cardiovascular risk (irrespective of traditional risk factors and high-risk plaque features). Both coronary artery disease and NAFLD share the same pathophysiology and metabolic profile. NAFLD can theoretically be a source/initiator for coronary artery disease (CAD). We aimed to study the association between NAFLD, CAD, the presence of high-risk plaque features, and the severity of stenosis.ResultsWe recruited 800 patients with suspected obstructive CAD and planned for coronary computed tomography angiography (CCTA), Exclusion criteria: heavy alcohol consumption; contraindications to contrast media; unevaluated coronary-artery segments; other known liver disease; and use of oral corticosteroids and/or amiodarone. Non-enhanced Computed Tomography abdomen was performed before the CCTA to detect NAFLD. To study the association between NAFLD and the presence of CAD, patients were classified as to either have, or not have CAD. The CAD group were then further studied for the presence of high-risk plaque features: napkin ring sign, Positive remodelling, Low Hounsfield unit (HU), and Spotty calcium; and their association with NAFLD. Thirty-two per cent of patients had NAFLD and 45% had CAD. A significant association between NAFLD and CAD was found (OR 4.21, 95% CI (confidence interval) (2.83–6.25), p = 0.000). In CAD patients, significant associations were present between NAFLD and high-risk plaque features: Napkin ring sign, Positive remodelling, Low HU, and Spotty calcium (OR 7.88, 95% CI (4.39–14.12), p < 0.001, OR 5.84, 95% (3.85–8.85), p < 0.001, OR 7.25, 95% CI (3.31–15.90), p < 0.001 and OR 6.66, 95% CI (3.75–11.82), p < 0.001), respectively. NAFLD was present in 39.30%, 50.00%, 20.00%, 54.50% and 100.00% of patients with CAD; and 1–24%; 25–49%; 50–69%; 7 = 0–99%, LMD (Left Main Disease) > 50% stenosis or 3V disease, and Total occlusion, respectively, p < 0.001.ConclusionsNAFLD is strongly associated with CAD, high-risk plaque features and higher grade of stenosis.

Carotid Plaque Composition Assessed by CT Predicts Subsequent Cardiovascular Events among Subjects with Carotid Stenosis.

Currently, the characteristics of carotid plaques are considered important factors for identifying subjects at high risk of stroke. This study aimed to test the hypothesis that carotid plaque composition assessed by CTA is associated with an increased risk of future major adverse cardiovascular events among asymptomatic subjects with moderate-to-severe carotid artery stenosis. This single-center, retrospective cohort study included 194 carotid plaques from 176 asymptomatic subjects with moderate-to-severe carotid artery stenosis. The association of CTA-determined plaque composition with the risk of subsequent adverse cardiovascular events was analyzed. During a median follow-up of 41 months, the adverse cardiovascular event incidence among 194 carotid plaques was 19.6%. There were significant differences in plaque Hounsfield units (P < .001) and spotty calcium presence (P < .001) between carotid plaques from subjects with and without subsequent adverse cardiovascular events. Multivariable analysis revealed carotid plaque Hounsfield unit density (P < .001) and spotty calcium (P < .001) as independent predictors of subsequent adverse cardiovascular events. In association with moderate carotid artery stenosis, the plaque Hounsfield unit values were significantly lower among carotid plaques from subjects who experienced subsequent adverse cardiovascular events (P = .002), strokes (P = .01), and cardiovascular deaths (P = .04); the presence of spotty calcium was significantly associated with the occurrence of adverse cardiovascular events (P = .001), acute coronary syndrome (P = .01), and cardiovascular death (P = .04). Carotid plaque Hounsfield unit density and spotty calcium were independent predictors of a greater risk of adverse cardiovascular event occurrence.

Association of coronary artery calcium score groups with qualitative and quantitatively assessed adverse plaque

Abstract Introduction Coronary artery calcification is a marker of cardiovascular risk, but its association with qualitatively and quantitatively assessed plaque subtypes on coronary computed tomography (CT) angiography (CCTA) is unknown. Methods In this post-hoc analysis, CT images and clinical outcomes were assessed in SCOT-HEART trial participants. Agatston coronary artery calcium score (CACS) was measured on non-contrast CT and was stratified as zero (0 Agatston units, AU), minimal (1 to 9AU), low (10 to 99AU), moderate (100 to 399AU), high (400 to 999AU) and very high (≥1000AU). Adverse plaques were investigated with qualitative (visual categorisation of positive remodelling, low-attenuation plaque, spotty calcification, napkin ring sign) and quantitative (calcified, non-calcified, low-attenuation and total plaque burden) methods. Results Images of 1769 patients were assessed (mean age 58±9 years, 56% male, median Agatston score 21 [interquartile range 0 to 230] AU). Of these 36% had a zero, 9% minimal, 20% low, 17% moderate, 10% high and 8% very high CACS. Amongst patients with a zero CACS, 14% had nonobstructive disease, 2% had obstructive disease, 2% had visually assessed adverse plaques and 13% had quantitative low-attenuation plaque (LAP) burden &amp;gt;4% (Figure 1). Non-calcified and low-attenuation plaque burden increased between patients with zero, minimal and low CACS (p&amp;lt;0.001), but there was no difference between those with medium, high and very high CACS. Over a median follow-up of 4.8 [4.1 to 5.7] years, fatal or non-fatal myocardial infarction occurred in 41 patients, 10% of whom had zero CACS. CACS ≥1000AU (Hazard ratio (HR) 4.55 [1.20 to 17.3], p=0.026) and low-attenuation plaque burden (HR 1.74 [1.19 to 2.54], p=0.004) were the only predictors of myocardial infarction, independent of obstructive disease and cardiovascular risk score. Figure 2 shows example CCTA images in a patient with zero CACS, non-calcified plaque (red), low attenuation plaque (orange) burden &amp;gt;4% and obstructive disease in the left anterior descending coronary artery. Conclusions In patients with stable chest pain, a zero CACS is associated with a good prognosis, but 1 in 6 have coronary artery disease, including the presence of adverse plaques. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation, National Institute of Health/National Heart, Lung, and Blood Institute

High peri-coronary inflammation assessed by coronary CT angiography predicts cardiovascular events in type 2 diabetes mellitus patients

Abstract Background Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular (CV) events, therefore there is a need to identify T2DM patients at higher risk. A novel imaging biomarker, the peri-coronary adipose tissue (PCAT) attenuation on coronary CT angiography (CTA), reflects peri-coronary inflammation. We hypothesized that the assessment of PCAT attenuation is useful for risk stratification in T2DM patients. Purpose We aimed to investigate whether high PCAT attenuation is related to increased risk of CV events in T2DM patients. Methods This study is a post-hoc analysis of the prospective cohort study consist of T2DM patients who underwent clinically indicated coronary CTA at a Japanese University Hospital. As CT findings, coronary artery calcium score, epicardial adipose tissue volume, high-risk plaque features (positive remodeling, low density plaque, spotty calcification), significant stenosis (&amp;gt;50% luminal narrowing), and PCAT attenuation were examined. PCAT attenuation was assessed in Hounsfield units (HU) of proximal 40-mm segments of the left anterior descending artery. CV events was defined as CV death, acute coronary syndrome, and hospitalization for heart failure. Results In a total of 333 T2DM patients (63% male, age 66±11 years), the mean PCAT attenuation was −70.6±6.1 HU. During the follow-up period of 4.2 years, 20 CV events (2 cases of CV death, 14 of acute coronary syndrome, 4 of heart failure) were confirmed. Patients with CV events had higher PCAT attenuation than those without CV events (−67.4 vs −70.8 HU, p=0.013). Multivariate linear regression analysis revealed that the independent determinants of PCAT attenuation were male (p&amp;lt;0.001) and statin use (p=0.024). In univariate Cox regression analyses, high-risk plaque features (HR 4.837, 95% CI 1.120–20.895, p=0.035), significant stenosis (HR 2.852, 95% CI 1.159–7.015, p=0.022), and PCAT attenuation (HR 1.119, 95% CI 1.34–1.212, p=0.005) were significantly associated with CV events. On the other hand, coronary artery calcium score (p=0.055) and epicardial adipose tissue volume (p=0.449) were not significantly associated with CV events. In multivariate Cox regression analysis, PCAT attenuation was independently associated with CV events after adjustment for coronary CTA findings and traditional CV risk factors (HR 1.105, 95% CI 1.017–1.200, p=0.018). Receiver operating characteristic curve analysis showed the optimal cut-off value of PCAT attenuation to predict CV events was −69.3 HU (sensitivity 58.5%, specificity 65.0%). Kaplan-Meier analysis showed that patients with high PCAT attenuation (≥−69.3 HU) had more CV events than those with low PCAT attenuation (p=0.013, log-rank test). Conclusion High PCAT attenuation was a strong predictor of CV events in T2DM patients independent of coronary CTA findings and traditional risk factors. Our study suggested that assessment of PCAT attenuation could be a valuable tool for risk stratification in T2DM patients. Funding Acknowledgement Type of funding sources: None. Figure 1. Representative casesFigure 2. Kaplan-Meier curves

Adverse coronary plaque characteristics are more common in patients with diabetes

Abstract Introduction Diabetes mellitus (DM) is associated with increased cardiovascular morbidity and mortality. However, there is a lack of data about the prevalence of adverse coronary artery plaques characteristics in patients with DM. Purpose In our study we aimed to compare the prevalence of adverse atherosclerotic coronary artery plaque characteristics between patients with and without DM. Methods We have analyzed the data of patients who underwent coronary computed tomography angiography (CCTA) between October 2012 and December 2020. Our exclusion criteria were coronary anomaly, congenital or other structural heart disease, previous revascularization or heart transplantation, non-diagnostic image quality and no available data on the presence of DM. Patients were divided into two groups based on the presence of DM. Results In total, 11,357 patients were included in our study. Prevalence of DM was 14.5%. There were significant differences in age (63.2±9.5 vs 58.1±12.2 years, p&amp;lt;0.001) and major cardiovascular risk factors such as hypertension, dyslipidemia and smoking between the two groups (all p&amp;lt;0.05). We have measured higher coronary artery calcium score in patients with DM vs. without DM (424.3±744.0 vs 174.2±794.6, p&amp;lt;0.001). Obstructive coronary artery disease (stenosis &amp;gt;70%) was more frequent in the DM group (24.6% vs 10.5%, p&amp;lt;0.001). While 29.6% of patients without DM had at least one plaque with adverse characteristics, this rate was 38.9% in those with DM (positive remodeling: 19.6% vs 26.1%, low attenuation: 7.6% vs 10.2%, spotty calcium: 16.9% vs 21.6%, napkin-ring sign: 1.7% vs 2.6%, all p&amp;lt;0.05). Conclusions The prevalence of severe coronary artery stenosis and coronary plaques with adverse characteristics was higher in patients with DM. Multivariate analysis is needed to further explore this association. Funding Acknowledgement Type of funding sources: None.

Dual-energy CT plaque characteristics of post mortem thin-cap fibroatheroma in comparison to infarct-related culprit lesions.

Improvement of non-invasive identification of high-risk plaque may increase the preventive options of acute coronary syndrome. To describe the characteristics of thin-cap fibroatheroma (TCFA) in a post mortem model in comparison to characteristics of culprit lesions in patients with non-ST-elevation-myocardial-infarction (NSTEMI) using the dual energy computed tomography (DECT). Three post mortem hearts were prepared with iodine-contrast, inserted in a Kyoto phantom and scanned by DECT. Six TCFA were identified using histopathological analysis (cap thickness < 65μm and necrotic core > 10% of the plaque area). In the NSTEMI group, 29 patients were scheduled to DECT prior to coronary angiography and invasive treatment. Culprit lesions were identified blinded for the patient history by two independent invasive cardiologists using the coronary angiography. The DECT analysis of TCFA and culprit lesions was performed retrospectively with determination of effective atomic number (Effective-Z), Hounsfield Unit (HU), plaque type (non-calcified, predominantly non-calcified, predominantly calcified or calcified), spotty calcification,, plaque length, plaque volume and plaque burden and the remodeling index. The Effective-Z, HU and plaqueburden were significantly different between TCFA and culprit lesions (P < 0.05).The TCFA plaques were more calcified in comparison to culprit lesions (P < 0.05). No significant difference in the other plaque characteristics was observed. The use of DECT demonstrated different Effective-Z values and different characteristics of post mortem TCFA in comparison to in vivo culprit lesions. This finding may highlight, that not all TCFA should be considered as vulnerable.

Association Among Local Hemodynamic Parameters Derived From CT Angiography and Their Comparable Implications in Development of Acute Coronary Syndrome.

Background: Association among local hemodynamic parameters and their implications in development of acute coronary syndrome (ACS) have not been fully investigated.Methods: A total of 216 lesions in ACS patients undergoing coronary CT angiography (CCTA) before 1–24 months from ACS event were analyzed. High-risk plaque on CCTA was defined as a plaque with ≥2 of low-attenuation plaque, positive remodeling, spotty calcification, and napkin-ring sign. With the use of computational fluid dynamics analysis, fractional flow reserve (FFR) derived from CCTA (FFRCT) and local hemodynamic parameters including wall shear stress (WSS), axial plaque stress (APS), pressure gradient (PG) across the lesion, and delta FFRCT across the lesion (ΔFFRCT) were obtained. The association among local hemodynamics and their discrimination ability for culprit lesions from non-culprit lesions were compared.Results: A total of 66 culprit lesions for later ACS and 150 non-culprit lesions were identified. WSS, APS, PG, and ΔFFRCT were strongly correlated with each other (all p < 0.001). This association was persistent in all lesion subtypes according to a vessel, lesion location, anatomical severity, high-risk plaque, or FFRCT ≤ 0.80. In discrimination of culprit lesions causing ACS from non-culprit lesions, WSS, PG, APS, and ΔFFRCT were independent predictors after adjustment for lesion characteristics, high-risk plaque, and FFRCT ≤ 0.80; and all local hemodynamic parameters significantly improved the predictive value for culprit lesions of high-risk plaque and FFRCT ≤ 0.80 (all p < 0.05). The risk prediction model for culprit lesions with FFRCT ≤ 0.80, high-risk plaque, and ΔFFRCT had a similar or superior discrimination ability to that with FFRCT ≤ 0.80, high-risk plaque, and WSS, APS, or PG; and the addition of WSS, APS, or PG into ΔFFRCT did not improve the model performance.Conclusions: Local hemodynamic indices were significantly intercorrelated, and all indices similarly provided additive and independent predictive values for ACS risk over high-risk plaque and impaired FFRCT.

Focal Geometry and Characteristics of Erosion-Prone Coronary Plaques in vivo Angiography and Optical Coherence Tomography Study.

Objective: This study compared focal geometry and characteristics of culprit plaque erosion (PE) vs. non-culprit plaques in ST-segment elevated myocardial infarction (STEMI) patients in whom optical coherence tomography (OCT) identified PE as the cause of the acute event.Background: Culprit PE is a distinct clinical entity with specific coronary risk factors and its own tailored management strategy. However, not all plaques develop erosion resulting in occlusive thrombus formation.Methods: Between January 2017 and July 2019, there were 484 STEMI patients in whom OCT at the time of primary percutaneous intervention identified culprit lesion PE to be the cause of the event; 484 culprit PE were compared to 1,132 non-culprit plaques within 1,196 imaged vessels.Results: Culprit PE were highly populated at “hot spots” within the proximal 40 mm in the left anterior descending artery (LAD) and tended to cluster proximal to a nearby bifurcation mainly in the LAD. Minimal lumen area (MLA) <2.51 mm2 and AS (area stenosis) >64.02% discriminated culprit PE from non-culprit plaques. In the multivariable analysis, focal geometry (LAD location, distance from coronary ostium <40 mm, and location proximal to a nearby bifurcation), luminal narrowing (MLA <2.51 mm2, AS > 64.02%), and TCFA phenotype were independent predictors of culprit PE overall. Cholesterol crystals were predictive of culprit PE with underlying LRP morphology while the absence of calcification and microchannels were risk factors for culprit PE with an underlying non-LRP. Similarities and differences in predictors of culprit PE were found between males and females; distance from coronary ostium <40 mm, MLA <2.51 mm2, TCFA, and less spotty calcium were risk factors of culprit PE in males, but not in females while smaller RVD was associated with culprit PE only in females.Conclusions: Irrespective of underlying lesion substrates and patient risk factors, there are lesion-specific and OCT-identifiable predictors of developing culprit PE in erosion-prone vulnerable patients.