Calcified versus non-calcified plaque volume fraction in patients with coronary artery disease and their association with outcome

Background The amount of coronary artery calcification is a general marker of coronary atherosclerosis and has been associated with increased risk of adverse cardiac events. On the other hand, calcification of coronary artery plaques has also been considered as a marker of plaque stabilization. Purpose We hypothesized that the fraction of the non-calcified volume of the total plaque volume in patients with coronary artery disease (CAD) is associated with abnormal myocardial perfusion and increased risk of future cardiac events. Methods Consecutive patients with suspected CAD undergoing sequential coronary computed tomography angiography (CCTA) with selective positron emission tomography (PET) perfusion imaging between 2007 and 2011 were selected. The total, calcified and non-calcified plaque volume (PV) were defined at patient-level. The non-calcified plaque volume fraction was calculated by dividing the non-calcified PV by the total PV, and expressed as percentage. Patients were divided into three groups: patients with 1) non-obstructive CAD (<50% diameter stenosis), 2) suspected coronary stenosis but normal PET perfusion and 3) suspected stenosis and abnormal regional PET perfusion. Difference between high vs. low PV was based on the median value. Clinical outcomes including all-cause mortality and myocardial infarction were recorded for 6.1 [SD 5.3–7.5] years. Results In total, 494 patients (age 63±9 years, 55% male) with documented atherosclerosis on CCTA were included. Total PV, calcified PV and non-calcified PV were all significantly larger in patients with abnormal myocardial perfusion compared to patients with non-obstructive CAD (370 [197–739] mm3 vs. 108 [59–177] mm3, 84 [23–220] mm3 vs. 9 [1–34] mm3 and 274 [157–500] mm3 vs. 94 [53–140] mm3, respectively, p<0.001 for all). However, the non-calcified fraction was smaller in patients with reduced myocardial perfusion (75 [63–86]% vs. 89 [76–98]%, p<0.001, Figure 1). During follow-up 35 events occurred. Patients with higher total PV, calcified PV and non-calcified PV showed worse outcome compared to patients with lower PV (log-rank p<0.001, Figure 2). In contrast, patients with a lower non-calcified plaque volume fraction showed poorer outcome (log-rank χ2=5.54; p=0.019) even after adjusting for statin therapy or revascularization. Conclusion We observed that higher volumes of any plaque component in general are associated with abnormal perfusion and increased risk of future cardiac events. In contrast, patients with a lower non-calcified plaque volume fraction showed poorer outcome. FUNDunding Acknowledgement Type of funding sources: None. Non-calcified plaque volume fraction Kaplan-Meier survival analysis

Usefulness of MCP-1 Chemokine in the Monitoring of Patients with Coronary Artery Disease Subjected to Intensive Dietary Intervention: A Pilot Study

Monocyte chemotactic protein-1 (MCP-1) plays an important role in the entire atherosclerotic process, from atherogenesis to destabilisation of the atherosclerotic plaque. The purpose of this study is to evaluate the effect of the dietary approaches to stop hypertension (DASH) diet in patients with coronary artery disease on the MCP-1 plasma concentration and to evaluate the potential usefulness of this chemokine as a marker of change in the volume and composition of coronary plaque. Material and method. As part of the dietary intervention to stop coronary atherosclerosis in computed tomography (DISCO-CT) study, patients were randomised to an intervention group (n = 40) in which the DASH diet was introduced, and to a control group (n = 39) with no dietary intervention. In the DASH group, dietary counselling was provided at all follow-up visits within 12 months of the follow-up period. MCP-1 plasma concentration was determined using enzyme-linked immunosorbent assay (ELISA). Coronary plaque analysis was performed using a semi-automated plaque analysis software system (QAngioCT, Medis, the Netherlands). Results. In the DASH group, MCP-1 plasma concentration significantly decreased by 34.1 pg/mL (p = 0.01), while in the control group, the change in MPC-1 was not significant. Significant inverse correlations were revealed for the change in MCP-1 plasma concentration and change in the consumption of vitamin C and dietary fibre both in the DASH (r = −0.519, p = 0.0005; r = −0.353, p = 0.025, respectively) and in the control group (r = −0.488 p = 0.001; r = −0.502, p = 0.001, respectively). In patients with the highest decrease in percent atheroma volume (PAV), a significant positive correlation was observed between the change in MCP-1 plasma concentration and changes in PAV (r = 0.428, p = 0.033) and calcified plaque component (r = 0.468, p = 0.018), while the change in noncalcified plaque component correlated inversely with change in MCP1 (r = −0.459, p = 0.021). Conclusion. Dietary intervention based on the DASH diet model reduces the MCP-1plasma concentration, mostly due to an increased intake of plant-derived, fibre-rich foods and antioxidants. The change in MCP-1 plasma concentration seems to reflect changes in the atheroma volume and proportions between the calcified and non-calcified plaque elements.

Blood iron level and vulnerable coronary atherosclerotic plaques

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Science Centre, Poland BACKGROUND Vulnerable plaque rupture is one of the causes of acute coronary syndromes. Preliminary research indicate that iron might accelerate the oxidation of low density lipoproteins (LDL) which can then be taken up by the LDL receptor on macrophages leading to their development into foam cells. Foam cell infiltration and necrotic core expansion are key events in atherogenesis and vulnerable plaque formation. However, the potential pathophysiological roles of iron in plaque development remain uncertain. PURPOSE The aim of the study was to investigate the relationship between iron and the type and composition of atherosclerotic plaques in the coronary arteries. METHODS In 200 patients with ≥1 stenosis ≥50% in computed tomography coronary angiography (CTCA) made for clinical indications we assessed: free iron level, the presence of high-risk plaque features: low-attenuation plaque (LAP), napkin-ring sign (NRS), positive remodeling (PR) and spotty calcium (SC) (CT Coronary, Syngo, Siemens), type of plaque (calcified, mixed, non-calcified) and their composition (calcified, fibrous, fibro-fatty, necrotic core) (QAngioCT, Medis). Fibro-fatty and necrotic core were analyzed together as vulnerable plaque component. The study was financed by the National Science Centre (2016/21/N/NZ5/01450). RESULTS Of 200 patients (125 men, 66 ± 10 years), the mean iron level (µg/dl) was 91 ±30 for women and 103 ±33 for men (p = 0.5). 3 patients had iron deficiency and 2 patients had iron overload. In CTCA analysis there were 815 calcified, 344 non-calcified and 438 mixed plaques. There was a trend in correlation between iron level and non-calcified plaque presence (p = 0.06). LAP was detected in 56 patients, NRS in 83, PR in 132, and SC in 125. Patients with LAP had higher iron levels (113 vs 93 µg/dl; p < 0.001). There was no association between iron and NRS, PR or SC (p > 0.05). In univariate regression analysis, the predictors of LAP were iron (p < 0.001) and male gender (p = 0.01). In multivariate regression analysis, iron was an independent predictor of LAP (p < 0.001; OR 1.02; 95%CI 1.01-1.03). Higher iron levels correlated with more fibro-fatty (p = 0.009) and necrotic core (p = 0.02); less calcified (p = 0.04); and with no relation to fibrous (p = 0.9), thus higher iron levels were associated with greater vulnerable plaque component (p = 0.003). CONCLUSIONS Higher iron levels are more likely to be associated with low-attenuation plaque and a greater vulnerable component of atherosclerotic plaques.

Collagenous Alzheimer amyloid plaque component impacts on the compaction of amyloid-β plaques

Massive deposition of amyloid β peptides (Aβ) as senile plaques (SP) characterizes the brain pathology of Alzheimer’s disease (AD). SPs exhibit a variety of morphologies, although little is known about the SP components that determine their morphology. Collagenous Alzheimer amyloid plaque component (CLAC) is one of the major non-Aβ proteinaceous components of SP amyloid in AD brains. Here we show that overexpression of CLAC precursor (CLAC-P) in the brains of APP transgenic mice results in a significant remodeling of amyloid pathology, i.e., reduction in diffuse-type amyloid plaques and an increase in compact plaques laden with thioflavin S-positive amyloid cores. In vivo microdialysis revealed a significant decrease in Aβ in the brain interstitial fluid of CLAC-P/APP double transgenic mice compared with APP transgenic mice. These findings implicate CLAC in the compaction of Aβ in amyloid plaques and the brain dynamics of Aβ.

Characterization of plaque features exhibiting physiological mismatch between fractional flow reserve and resting index: near-infrared spectroscopy imaging analysis

Background In addition to fractional flow reserve (FFR), resting indexes (RI) have been shown as another physiological measure to evaluate myocardial ischemia. Despite the clinical usefulness of RI without the use of intravenous vasodilatory agent, discrepancy between FFR and RI infrequently occurs. Whether this physiological mismatch is derived by specific plaque feature remains unknown. Purpose To characterize coronary plaques associated with coronary physiological mismatch. Methods We analyzed 59 coronary arteries (LAD/RCA/LCX=49/4/6) with FFR≤0.80 in 57 stable CAD subjects receiving PCI. Following measurement of FFR and RI, culprit lesion was evaluated by near-infrared spectroscopy and intravascular ultrasound (NIRS/IVUS). The analyzed vessels were stratified according to FFR and RI values: FFR≤0.75+RI>0.89 (n=6: physiological mismatch), FFR>0.75+RI>0.89 (n=6), FFR≤0.75+RI≤0.89 (n=33) and FFR>0.75+RI≤0.89 (n=14). Results The median values of percent diameter stenosis, FFR and RI were 51%, 0.75 and 0.87, respectively. Physiological mismatch was observed in 10.1% (=6/59) of analyzed vessels. On IVUS imaging, maximum percent plaque area was greater than 70% in all groups (p=0.29). Furthermore, there were no significant differences in angiographic and IVUS-derived minimum lumen area across 4 groups (Table). However, culprit lesions exhibiting physiological mismatch contained a substantially larger amount of lipid plaque, reflected by a higher maximum 4-mm lipid-core burned index (maxLCBI4mm: p=0.04) on NIRS imaging (Table). Multivariate analysis demonstrated maxLCBI4mm as the only plaque feature associated with physiological mismatch (odds ratio=1.010, 95% CI: 1.001–1.019, p=0.02). Conclusion Plaque feature associated with coronary physiological mismatch was the extent of lipidic materials but not the quantity of coronary atheroma. Since the accumulation of lipidic plaque component is caused by endothelial dysfunction, this vascular substrate could impair baseline vasomotion, thereby causing a lower FFR despite preserved RI value. Evaluation of lipidic burden may be a potential option to avoid unnecessary deferral of revascularization in subjects with normal RI value. maxLCBI4mm in each group Funding Acknowledgement Type of funding source: None

High-risk plaque regression after intensive dietary intervention in patients with non-obstructive coronary artery disease: a randomised computed tomography angiography study (DISCO-CT)

Background Lifestyle and diet modification are the forefront in the management of coronary artery disease (CAD), however, there is no data whether they may stop progression of atheroslcerosis. Some coronary plaque characteristics are known to increase the risk of future cardiovascular events independently of coronary stenosis severity. These plaques are characterized by the presence of lipids and necrotic elements, and can be identified with coronary computed tomography angiography (CTA). Purpose To study the effect of intensive dietary intervention on changes in atherosclerotic plaque volume and composition. Methods We enrolled 89 patients (41% women, mean age 60±7.7 years) with nonobstructive coronary lesions (<70% stenosis) identified by CTA (2x192-multislice scanner, temporal resolution 66 ms), qualified to medical treatment. All participants were subjected to optimal medical therapy (OMT). Patients were randomised (1:1) to either A) OMT with regular follow-up (after 1, 3, 6, 9 and 12 months) by a dietitian to stick to Dietary Approaches to Stop Hypertension (DASH) model, or B) routine management, ie. OMT alone. CTA was repeated in all patients after the mean time of 66.9±13.7 weeks. An experienced observer blinded to the allocated treatment group and other clinical data evaluated all of the scans. The outcome was change in total plaque volume, percent plaque volume and plaque composition, assessed with a dedicated software system. Based on tissue attenuation ranges in Hounsfield units (HU), the following components of atheroma were distinguished: dense calcium (>351 HU), fibrous plaque (151 to 350 HU), and fibrofatty plaque plus necrotic core (−100 to 150 HU), regarded as the vulnerable plaque component. Results Total plaque volume did not change significantly in any group (p=0.41; Figure 1A). Percent atheroma volume increased in the control arm vs. no significant change in the experimental arm, with no significant intergroup difference (p=0.79; Figure 1B). Vulnerable plaque component decreased in both subgroups, by 52.9±82.2 mm3 in the experimental vs. 20.8±58.5 mm3 in the control arm, and there was a significant difference in the reductions between the groups (p=0.04; Figure 1C). Fibrous plaque volume and dense calcium volume did not change significantly in any group (+9.5±117.8 mm3 in the experimental vs. +7.6±92.1 mm3 in the control arm, p=0.93, and +33±68.9 mm3 vs. +30.2±52.5 mm3, p=0.78, respectively). Conclusions Intensive diet intervention atop OMT can stop the progression of atherosclerosis and lead to a significant reduction in vulnerable plaque component compared to OMT alone. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Institute of Cardiology in Warsaw, Poland

A Machine Learning-Based Method for Intracoronary OCT Segmentation and Vulnerable Coronary Plaque Cap Thickness Quantification

Accurate cap thickness quantification is of fundamental importance for vulnerable plaque detection in cardiovascular research. A segmentation method for intracoronary optical coherence tomography (OCT) image based on least squares support vector machine (LS-SVM) was performed to characterize plaque component borders and quantify fibrous cap thickness. Manual segmentation of OCT images were performed by experts based on combination of virtual-histology intravascular ultrasound (VH-IVUS) and OCT images and used as gold standard. The segmentation methods based on LS-SVM provided accurate plaque cap thickness (an 8.6% error by LS-SVM vs. 71% error by IVUS50) serving as solid basis for plaque modeling and assessment.

Automatic Thin Cap Fibroatheroma Detection Using Fusion of Intravascular Ultrasound and Virtual Histology Images

Virtual Histology- Intravascular Ultrasound (VH-IVUS) image is an available method for visualizing plaque component to detect thin cap fibroatheroma. Nevertheless, this imaging modality has considerable limitations to extract the plaque component features and identifying the TCFA plaque. The aim of this paper is to improve the identification of TCFA using fusion of IVUS and VH-IVUS images. In order to generate the automatic technique for reducing the human interaction, a new method namely Active Contour based Plaque Border Detection (ACPB) is proposed. In order to perform the pixel wise classification, hybrid of K-means algorithm with Particle Swarm Optimization and Plaque based Minimum Euclidean Distance (KMPSO-PMED) method is presented to classify the plaque region as well. Moreover, to obtain more significant information of imaging modalities, fusion of two different images consisting of VH-IVUS and IVUS is performed. Therefore, geometric features are extracted from the plaque region and combine with IVUS features. Furthermore, different group of plaque features are divided by means of the histopathological studies. SVM classifiers is applied to detect the TCFA and non-TCFA plaques. The proposed method is applied on 566 in-vivo IVUS and their matching VH-IVUS images obtained from 9 patients. The best result of SVM illustrates the accuracy rates of 99.41% for classification of TCFA plaque. The results prove that the highest accuracy is achieved by integrated features of IVUS and VH-IVUS images.