Thin-cap Fibroatheroma Lesions Research Articles

Medically Treated Nonischemic Thin-Cap Fibroatheroma Lesions Versus Fractional Flow Reserve-Guided Complete Revascularization in Diabetic Patients

BackgroundFractional flow reserve (FFR) is an established method to guide decisions on revascularization; however, in patients with diabetes mellitus (DM), FFR-negative lesions carrying an optical coherence tomography-detected thin-cap fibroatheroma (TCFA) remain at high risk for adverse cardiac events. MethodsIn this prespecified subanalysis of the COMBINE OCT-FFR trial, DM patients with ≥1 FFR-negative, TCFA-positive medically treated target lesions referred to as vulnerable plaque (VP group), were compared to patients with exclusively FFR-positive target lesions who underwent complete revascularization (CR group). The primary endpoint was first and recurrent event analysis for target lesion failure and the secondary endpoint was a composite of cardiac death, target vessel myocardial infarction, target lesion revascularization, or hospitalization due to unstable angina. ResultsAmong 550 patients enrolled, 98 belonged to the VP group while 93 to the CR group and were followed up to 5 years. The VP group had a higher occurrence of the primary endpoint (20.4% vs 8.6%; HR, 2.22; 95% CI, 0.98-5.04; P = .06). Recurrent event analysis showed that the VP group had significantly higher rates of the primary and secondary endpoints (9.17 vs 3.76 events per 100 PY; RR, 2.44; 95% CI, 1.16-5.60; P = .01 and 13.45 vs 5.63 events per 100 PY; RR, 2.39; 95% CI, 1.30-4.62; P < .01). ConclusionsIn a population with DM, medically treated nonischemic, TCFA-carrying target lesions were associated with higher risk of reoccurring adverse cardiac events compared to target lesions that underwent complete revascularization, opening the discussion about whether a focal preventive revascularization strategy could be contemplated for highly vulnerable lesions.

Pericoronary Adipose Tissue Radiomics from Coronary Computed Tomography Angiography Identifies Vulnerable Plaques

Pericoronary adipose tissue (PCAT) features on Computed Tomography (CT) have been shown to reflect local inflammation and increased cardiovascular risk. Our goal was to determine whether PCAT radiomics extracted from coronary CT angiography (CCTA) images are associated with intravascular optical coherence tomography (IVOCT)-identified vulnerable-plaque characteristics (e.g., microchannels (MC) and thin-cap fibroatheroma (TCFA)). The CCTA and IVOCT images of 30 lesions from 25 patients were registered. The vessels with vulnerable plaques were identified from the registered IVOCT images. The PCAT-radiomics features were extracted from the CCTA images for the lesion region of interest (PCAT-LOI) and the entire vessel (PCAT-Vessel). We extracted 1356 radiomic features, including intensity (first-order), shape, and texture features. The features were reduced using standard approaches (e.g., high feature correlation). Using stratified three-fold cross-validation with 1000 repeats, we determined the ability of PCAT-radiomics features from CCTA to predict IVOCT vulnerable-plaque characteristics. In the identification of TCFA lesions, the PCAT-LOI and PCAT-Vessel radiomics models performed comparably (Area Under the Curve (AUC) ± standard deviation 0.78 ± 0.13, 0.77 ± 0.14). For the identification of MC lesions, the PCAT-Vessel radiomics model (0.89 ± 0.09) was moderately better associated than the PCAT-LOI model (0.83 ± 0.12). In addition, both the PCAT-LOI and the PCAT-Vessel radiomics model identified coronary vessels thought to be highly vulnerable to a similar standard (i.e., both TCFA and MC; 0.88 ± 0.10, 0.91 ± 0.09). The most favorable radiomic features tended to be those describing the texture and size of the PCAT. The application of PCAT radiomics can identify coronary vessels with TCFA or MC, consistent with IVOCT. Furthermore, the use of CCTA radiomics may improve risk stratification by noninvasively detecting vulnerable-plaque characteristics that are only visible with IVOCT.

TCT-89 Morphological Characteristics of Thin-Cap Fibroatheroma Lesions in Patients With and Without Future Adverse Events: Insights From the COMBINE (OCT-FFR) Study

TCT-89 Morphological Characteristics of Thin-Cap Fibroatheroma Lesions in Patients With and Without Future Adverse Events: Insights From the COMBINE (OCT-FFR) Study

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.

CT texture analysis of vulnerable plaques on optical coherence tomography

PurposeTo explore whether CT texture analysis can identify thin-cap fibroatheroma (TCFA) determined by optical coherence tomography (OCT). MethodsThirty-three patients with 43 lesions who underwent both CCTA and OCT within 3 months were retrospectively included. 12 conventional CT-derived plaque features, fat attenuation index (FAI) and 1691 plaque radiomics features were extracted to discriminate TCFA lesions and non-TCFA lesions determined by OCT. Minimum redundancy and maximum relevance (mRMR) method was employed to select radiomics features. The top ranked features were used to construct a forward stepwise logistic radiomics model. The performance of radiomics model was compared with the conventional high-risk plaque (HRP) features model and FAI model for the detection of TCFA. ResultsOut of 1691 features, 35 features were significantly different between TCFA and non-TCFA lesions (all p＜0.05) while only low attenuation plaque (LAP) was more frequent in TCFA group (p = 0.004). There was no significant difference in FAI between TCFA and non-TCFA lesions. Five features were ultimately integrated into the radiomics model after mRMR analysis, which demonstrated significantly higher AUC for the detection of TCFA (0.952; 95 % CI: 0.897–1.000) compared with the conventional HRP features model (0.621; 95 % CI: 0.469−0.773, p < 0.001) and FAI model (0.52; 95 % CI: 0.33−0.70, p < 0.001). ConclusionCT texture analysis performs better at identifying TCFA determined by OCT compared with conventional CT-derived plaque parameters and FAI. Texture analysis may serve as a potential non-invasive method of evaluating vulnerable plaque.

Nonculprit Lesion Plaque Morphology in Patients With ST-Segment-Elevation Myocardial Infarction: Results From the COMPLETE Trial Optical Coherence Tomography Substudys.

Complete revascularization with routine percutaneous coronary intervention of nonculprit lesions after primary percutaneous coronary intervention improves outcomes in ST-segment-elevation myocardial infarction. Whether this benefit is associated with nonculprit lesion vulnerability is unknown. In a prospective substudy of the COMPLETEs trial (Complete vs Culprit-Only Revascularization to Treat Multi-Vessel Disease After Early PCI for STEMI), we performed optical coherence tomography of at least 2 coronary arteries before nonculprit lesion percutaneous coronary intervention in 93 patients with ST-segment-elevation myocardial infarction and multivessel disease; and the ST-segment-elevation myocardial infarction culprit vessel if there was unstented segment amenable to imaging. Nonculprit lesions were categorized as obstructive (≥70% stenosis by visual angiographic assessment) or nonobstructive, and as thin-cap fibroatheroma (TCFA) or non-TCFA by optical coherence tomography criteria. TCFA was defined as a lesion with mean fibrous cap thickness <65 μm overlying a lipid arc >90°. On a patient level, at least one obstructive TCFA was observed in 44/93 (47%) of patients. On a lesion level, there were 58 TCFAs among 150 obstructive nonculprit lesions compared with 74 TCFAs among 275 nonculprit lesions (adjusted TCFA prevalence: 35.4% versus 23.2%, P=0.022). Compared with obstructive non-TCFAs, obstructive TCFAs had similar lesion length (23.1 versus 20.8 mm, P=0.16) but higher lipid quadrants (55.2 versus 19.2, P<0.001), greater mean lipid arc (203.8° versus 84.5°, P<0.001), and more macrophages (97.1% versus 54.4%, P<0.001) and cholesterol crystals (85.8% versus 44.3%, P<0.001). For nonobstructive lesions, TCFA lesions had similar lesion length (16.7 versus 14.6 mm, P=0.11), but more lipid quadrants (36.4 versus 13.5, P<0.001), and greater mean lipid arc (191.8° versus 84.2°, P<0.001) compared with non-TCFA. Among patients who underwent optical coherence tomography imaging in the COMPLETE trial, nearly 50% had at least one obstructive nonculprit lesion containing complex vulnerable plaque. Obstructive lesions more commonly harbored vulnerable plaque morphology than nonobstructive lesions. This may help explain the benefit of routine percutaneous coronary intervention of obstructive nonculprit lesions in patients with ST-segment-elevation myocardial infarction and multivessel disease. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01740479s.

The value of quantified plaque analysis by dual-source coronary CT angiography to detect vulnerable plaques: a comparison study with intravascular ultrasound.

To investigate the diagnostic performance of quantified plaque analysis and high-risk plaque characterization by coronary computed tomography angiography (CCTA) for identifying thin-cap fibroatheroma (TCFA). Patients who underwent both CCTA and intravascular ultrasound (IVUS) within 4 weeks were retrospectively included. CT-derived quantitative and qualitative parameters, including diameter stenosis, minimal lumen area (MLA), low attenuation plaque (LAP) volume napkin-ring sign (NRS), positive remodeling (PR) and spotty calcification, were recorded. TCFA lesions and non-TCFA lesions were determined by IVUS. Multivariate regression analysis was used to determine the independent predictors of TCFA lesions. Sixty-five patients (mean age: 69.8±9.2 years, 29 females) with 89 lesions were finally included. LAP and NRS were more frequently presented in the group of TCFA lesions. The mean LAP volume of TCFA lesions was significantly larger than that of non-TCFA lesions [16.5 (11.0-23.0) vs. 0 (0-1.5) mm3, P<0.001]. According to multivariate logistic regression analysis, LAP volume was the only significant predictor for IVUS-confirmed vulnerable plaques (odds ratio =3.294, 95% confidence interval: 1.177-9.223, P=0.023). LAP volume showed largest area under curve (AUC) for diagnosing TCFA lesions (AUC =0.901, 95% confidence interval: 0.819-0.954, P<0.0001). When using >8 mm3 as the best cutoff value, the diagnostic accuracy, sensitivity and specificity of LAP volume for predicting TCFA lesions were 91.0% (81/89), 84.6% (22/26) and 96.8% (61/63) respectively. CT-derived LAP volume of TCFA lesions was significantly higher than those of non-TCFA lesions. LAP volume was the strongest predictor for TCFA lesions as validated by IVUS.

Adiponectin in Relation to Coronary Plaque Characteristics on Radiofrequency Intravascular Ultrasound and Cardiovascular Outcome

BackgroundProspective data on the associations of adiponectin with in-vivo measurements of degree, phenotype and vulnerability of coronary atherosclerosis are currently lacking.ObjectiveTo investigate the association of plasma adiponectin with virtual histology intravascular ultrasound (VH-IVUS)-derived measures of atherosclerosis and with major adverse cardiac events (MACE) in patients with established coronary artery disease.Methods In 2008-2011, VH-IVUS of a non-culprit non-stenotic coronary segment was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS, n = 318) or stable angina pectoris (SAP, n = 263) from the atherosclerosis-intravascular ultrasound (ATHEROREMO-IVUS) study. Blood was sampled prior to coronary angiography. Coronary plaque burden, tissue composition, high-risk lesions, including VH-IVUS-derived thin-cap fibroatheroma (TCFA), were assessed. All-cause mortality, ACS, unplanned coronary revascularization were registered during a 1-year-follow-up. All statistical tests were two-tailed and p-values < 0.05 were considered statistically significant.Results In the full cohort, adiponectin levels were not associated with plaque burden, nor with the various VH-tissue types. In SAP patients, adiponectin levels (median[IQR]: 2.9(1.9-3.9) µg/mL) were positively associated with VH-IVUS derived TCFA lesions, (OR[95%CI]: 1.78[1.06-3.00], p = 0.030), and inversely associated with lesions with minimal luminal area (MLA) ≤ 4.0 mm2 (OR[95%CI]: 0.55[0.32-0.92], p = 0.025). In ACS patients, adiponectin levels (median[IQR]: 2.9 [1.8-4.1] µg/mL)were not associated with plaque burden, nor with tissue components. Positive association of adiponectin with death was present in the full cohort (HR[95%CI]: 2.52[1.02-6.23], p = 0.045) and (borderline) in SAP patients (HR[95%CI]: 8.48[0.92-78.0], p = 0.058). In ACS patients, this association lost statistical significance after multivariable adjustment (HR[95%CI]: 1.87[0.67-5.19], p = 0.23).Conclusion In the full cohort, adiponectin levels were associated with death but not with VH-IVUS atherosclerosis measures. In SAP patients, adiponectin levels were associated with VH-IVUS-derived TCFA lesions. Altogether, substantial role for adiponectin in plaque vulnerability remains unconfirmed.

Fibrinogen in relation to degree and composition of coronary plaque on intravascular ultrasound in patients undergoing coronary angiography.

The aim of this study was to provide additional insight into the role of fibrinogen in coronary artery disease by investigating the associations between plasma fibrinogen with both degree and composition of coronary atherosclerosis as determined by virtual histology-intravascular ultrasound. In 581 patients undergoing coronary angiography for acute coronary syndrome (ACS) or stable angina pectoris, preprocedural blood samples were drawn for fibrinogen, C-reactive protein (CRP), interleukin-6, and plasminogen activator inhibitor-1 measurements, and virtual histology-intravascular ultrasound of a nonculprit coronary artery was performed. The degree [plaque volume, plaque burden (PB), and lesions with PB≥70%] and the composition of coronary atherosclerotic plaque (fibrous, fibrofatty, dense calcium, necrotic core tissue, and thin-cap fibroatheroma lesions) were assessed. Fibrinogen showed a tendency toward a positive association with PB [β (95% CI): 2.55 (-0.52-5.61) increase in PB per ln(g/l) fibrinogen, P=0.09], which was driven significantly by an association in the ACS subgroup [β (95% CI): 4.11 (0.01-8.21) increase in PB per ln(g/l) fibrinogen, P=0.049]. Fibrinogen was also related to the presence of lesions with PB 70% or more in both the full cohort [OR (95% CI): 2.27 (1.17-4.43), P=0.016] and ACS patients [OR (95% CI): 2.92 (1.17-7.29), P=0.022]. All associations were independent of established cardiovascular risk factors, but not CRP. Interleukin-6 and plasminogen activator inhibitor-1 did not provide incremental value to fibrinogen when examining the associations with degree of atherosclerosis. Substantial associations with plaque composition were absent. Fibrinogen is associated with degree of coronary atherosclerosis, especially in ACS patients. However, whether this association is independent of CRP might be questioned and needs further investigation.

Haptoglobin polymorphism in relation to coronary plaque characteristics on radiofrequency intravascular ultrasound and near-infrared spectroscopy in patients with coronary artery disease

BackgroundConflicting results exist regarding the association between a common Haptoglobin (Hp) polymorphism and risk of coronary artery disease. We investigated the association of three functionally different anti-oxidant and anti-inflammatory Hp phenotypes (Hp1-1, Hp2-1, Hp2-2) with invasively measured degree and composition of coronary atherosclerosis as determined by intravascular ultrasound (-virtual histology) (IVUS(-VH)) as well as near-infrared spectroscopy (NIRS). MethodsNon-culprit coronary artery segments of 581 patients with acute coronary syndrome (ACS) or stable angina pectoris were imaged with IVUS(-VH). In 203 patients, the segments were also imaged with NIRS. Pre-procedural blood samples were drawn for Hp phenotyping. Degree (segment plaque volume, segment plaque burden (PB); presence of lesions with PB≥70%) and composition (segment fractions of fibrous, fibro-fatty, dense calcium, and necrotic core tissue; presence of IVUS-VH derived thin-cap fibroatheroma lesions) of coronary atherosclerosis were measured. ResultsNo differences were present between the three Hp phenotypes with regard to degree and composition of coronary atherosclerosis in the full cohort. However, ACS patients with a Hp2-1 or Hp2-2 phenotype had a higher segment PB percentage (β[95% CI]: 3.88[0.31–7.44], p=0.033), increased prevalence of lesions with PB≥70% (OR[95% CI]: 3.61[1.06–12.30], p=0.040), and a tendency towards a higher segment plaque volume (β[95% CI]: 1.29[−0.04–2.62], p=0.056) in multivariable analyses. ConclusionsAlthough in the full cohort no associations could be demonstrated between Hp phenotypes and plaque characteristics, a significant association was present between phenotypes resulting from a genotype containing a Hp2 allele (Hp2-1 or Hp2-2) and a higher degree of atherosclerosis in patients with ACS.

PCSK9 in relation to coronary plaque inflammation: Results of the ATHEROREMO-IVUS study

Background and aimsExperimental studies have suggested that proprotein convertase substilisin/kexin type 9 (PCSK9) might directly promote inflammatory processes contributing to atherosclerosis by mechanisms independent of low-density lipoprotein (LDL) cholesterol levels. This study aims to investigate the association between serum PCSK9 levels and the fraction and amount of necrotic core tissue in coronary atherosclerotic plaque, as assessed by intravascular ultrasound virtual histology (IVUS-VH) imaging. MethodsBetween 2008 and 2011, IVUS-VH imaging of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for acute coronary syndrome (ACS) or stable angina. PCSK9 concentrations were measured in serum samples that were drawn prior to coronary angiography. None of the patients received PCSK9 inhibitors. ResultsAfter adjustment for established cardiac risk factors, statin use and serum LDL cholesterol, serum PCSK9 levels were linearly associated with the fraction of plaque consisting of necrotic core tissue (β = 1.24% increase per 100 μg/L increase in PCKS9, 95%CI 0.55–1.94, p = 0.001) and with the absolute volume of necrotic core tissue (β = 0.09, 95%CI 0.01–0.18, p = 0.033), but were not significantly associated with plaque burden (p = 0.11), plaque volume (p = 0.22) or the presence of IVUS-VH-derived thin-cap fibroatheroma lesions (p = 1.0). ConclusionSerum PCSK9 levels were linearly associated with the fraction and amount of necrotic core tissue in coronary atherosclerosis, independently of serum LDL cholesterol levels and statin use. Therefore, PCSK9 may be an interesting therapeutic target for the treatment of atherosclerotic disease beyond LDL cholesterol regulation.

Smoking in Relation to Coronary Atherosclerotic Plaque Burden, Volume and Composition on Intravascular Ultrasound.

BackgroundThis study aimed to evaluate the relationship between cigarette smoking and coronary atherosclerotic burden, volume and composition as determined in-vivo by grayscale and virtual histology (VH) intravascular ultrasound (IVUS).Methods and ResultsBetween 2008 and 2011, (VH-)IVUS of a non-culprit coronary artery was performed in 581 patients undergoing coronary angiography. To account for differences in baseline characteristics, current smokers were matched to never smokers by age, gender and indication for catheterization, resulting in 280 patients available for further analysis. Coronary atherosclerotic plaque volume, burden, composition (fibrous, fibro-fatty, dense calcium and necrotic core) and high-risk lesions (VH-IVUS derived thin-cap fibroatheroma (TCFA), plaque burden ≥70%, minimal luminal area ≤4.0 mm2) were assessed. Cigarette smoking showed a tendency towards higher coronary plaque burden (mean±SD, 38.6±12.5% in current versus 36.4±11.0% in never smokers, p = 0.080; and odds ratio (OR) of current smoking for plaque burden above versus below the median 1.69 (1.04–2.75), p = 0.033). This effect was driven by an association in patients presenting with an acute coronary syndrome (ACS) (current smokers, plaque burden 38.3±12.8% versus never smokers, plaque burden 35.0±11.2%, p = 0.049; OR 1.88 (1.02–3.44), p = 0.042). Fibrous tissue tended to be lower in current smokers (mean±SD, 57.7±10.5% versus 60.4±12.6%, p = 0.050) and fibro-fatty tissue was higher in current smokers (median[IQR], 9.6[6.0–13.7]% versus 8.6[5.8–12.2]%, p = 0.039). However, differences in percentage necrotic core and dense calcium could not be demonstrated. Also, no differences were found with regard to high-risk lesions.ConclusionsAn association between smoking and degree of coronary atherosclerosis was present in patients undergoing coronary angiography who presented with ACS. Although smoking was associated with higher fibro-fatty percentage, no associations could be demonstrated with percentage necrotic core, nor with VH-IVUS derived TCFA lesions. Since the magnitude of the differences in both degree and composition of atherosclerosis was modest, clinical relevance of the findings may be questioned.

Circulating chemokines in relation to coronary plaque characteristics on radiofrequency intravascular ultrasound and cardiovascular outcome

Objective: To investigate relations of several circulating chemokines with extent and phenotype of coronary atherosclerosis and with 1-year clinical outcome.Methods: Intravascular ultrasound virtual histology (IVUS-VH) imaging of a coronary artery was performed in 581 patients. Monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), MIP-1β and regulated upon activation normal T cell expressed and secreted (RANTES) were measured in plasma.Results: Higher MCP-1, MIP-1α and lower RANTES were associated with coronary plaque burden. Higher MCP-1, MIP-1α and lower RANTES were associated with the presence of IVUS-VH-derived thin-cap fibroatheroma lesions. RANTES was associated with major adverse cardiac events.Conclusions: RANTES is a promising biomarker that is inversely associated with coronary plaque burden and vulnerability, as well as with death and acute coronary syndrome.Trial registration: ClinicalTrials.gov identifier: NCT01789411.

Relation of C-Reactive Protein to Coronary Plaque Characteristics on Grayscale, Radiofrequency Intravascular Ultrasound, and Cardiovascular Outcome in Patients With Acute Coronary Syndrome or Stable Angina Pectoris (from the ATHEROREMO-IVUS Study)

The relation between C-reactive protein (CRP) and coronary atherosclerosis is not fully understood. This study aims to investigate the associations among high-sensitivity CRP, coronary plaque burden, and the presence of high-risk coronary lesions as measured by intravascular ultrasound (IVUS) and 1-year cardiovascular outcome. Between 2008 and 2011, grayscale and virtual histology IVUS imaging of a nonculprit coronary artery was performed in 581 patients who underwent coronary angiography for acute coronary syndrome (ACS) or stable angina pectoris. Primary end point consisted of 1-year major adverse cardiac events (MACEs), defined as all-cause mortality, ACS, or unplanned coronary revascularization. After adjustment for established cardiac risk factors, baseline CRP levels were independently associated with higher coronary plaque burden (p = 0.002) and plaque volume (p = 0.002) in the imaged coronary segment. CRP was also independently associated with the presence of large lesions (plaque burden ≥70%; p = 0.030) but not with the presence of stenotic lesions (minimal luminal area ≤4.0 mm(2); p = 0.62) or IVUS virtual histology-derived thin-cap fibroatheroma lesions (p = 0.36). Cumulative incidence of 1-year MACE was 9.7%. CRP levels >3 mg/L were independently associated with a higher incidence of MACE (hazard ratio 2.17, 95% confidence interval [CI] 1.01 to 4.67, p = 0.046) and of all-cause mortality and ACS only (hazard ratio 3.58, 95% CI 1.04 to 13.0, p = 0.043), compared with CRP levels <1 mg/L. In conclusion, in patients who underwent coronary angiography, high-sensitivity CRP is a marker of coronary plaque burden but is not related to the presence of virtual histology-derived thin-cap fibroatheroma lesions and stenotic lesions. CRP levels >3 mg/L are predictive for adverse cardiovascular outcome at 1 year.

In vivo detection of high-risk coronary plaques by radiofrequency intravascular ultrasound and cardiovascular outcome: results of the ATHEROREMO-IVUS study

Acute coronary syndromes (ACS) are mostly caused by plaque rupture. This study aims to investigate the prognostic value of in vivo detection of high-risk coronary plaques by intravascular ultrasound (IVUS) in patients undergoing coronary angiography. Between November 2008 and January 2011, IVUS of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for ACS (n = 318) or stable angina (n = 263). Primary endpoint was major adverse cardiac events (MACEs) defined as mortality, ACS, or unplanned coronary revascularization. Culprit lesion-related events were not counted. Cumulative Kaplan-Meier incidence of 1-year MACE was 7.8%. The presence of IVUS virtual histology-derived thin-cap fibroatheroma (TCFA) lesions (present 10.8% vs. absent 5.6%; adjusted HR: 1.98, 95% CI: 1.09-3.60; P = 0.026) and lesions with a plaque burden of ≥70% (present 16.2% vs. absent 5.5%; adjusted HR: 2.90, 95% CI: 1.60-5.25; P < 0.001) were independently associated with a higher MACE rate. Thin-cap fibroatheroma lesions were also independently associated with the composite of death or ACS only (present 7.5% vs. absent 3.0%; adjusted HR: 2.51, 95% CI: 1.15-5.49; P = 0.021). Thin-cap fibroatheroma lesions with a plaque burden of ≥70% were associated with a higher MACE rate within (P = 0.011) and after (P < 0.001) 6 months of follow-up, while smaller TCFA lesions were only associated with a higher MACE rate after 6 months (P = 0.033). In patients undergoing coronary angiography, the presence of IVUS virtual histology-derived TCFA lesions in a non-culprit coronary artery is strongly and independently predictive for the occurrence of MACE within 1 year, particularly of death and ACS. Thin-cap fibroatheroma lesions with a large plaque burden carry higher risk than small TCFA lesions, especially on the short term.

Incidence, Predictors, and Clinical Impact of Tissue Prolapse after Coronary Intervention: An Intravascular Optical Coherence Tomography Study

Objectives: To evaluate the predictors of tissue prolapse after stenting and whether this phenomenon can affect the clinical outcome. Methods: All consecutive patients who underwent optical coherence tomography (OCT) examination after stent implantation were included. Qualitative and quantitative assessment of tissue prolapse after stent implantation was performed. The lesions were classified into 4 groups according to the severity of tissue prolapse. We analyzed the clinical, procedural, and image-based predictors of severe tissue prolapse and evaluated the clinical impact of tissue prolapse. Results: Tissue prolapse within the stented segment was visible in 102/104 (98.08%) cases. The frequency and severity of tissue prolapse was similar in acute coronary syndrome (ACS) and non-ACS lesions. The OCT-defined thin cap fibroatheroma (TCFA) was related with severe tissue prolapse (≧grade III) (r = 17.722, p < 0.001). No difference in events was observed among different tissue prolapse groups during the hospitalization period and 1-year follow-up. Conclusions: The incidence of tissue prolapse after stent implantation was relatively high, irrespective of the clinical presentation. OCT-defined TCFA lesions were more likely with severe tissue prolapse (≧grade III). Tissue prolapse was not associated with clinical events during the hospitalization period and 1-year clinical follow-up.

In-vivo detection of the frequency and distribution of thin-cap fibroatheroma and ruptured plaques in patients with coronary artery disease

The purpose of this study was to assess the prevalence and to quantify the thin-cap fibroatheroma (TCFA) and ruptured plaques in patients with coronary artery disease using optical coherence tomography (OCT). TCFA lesions are the most prevalent precursors of plaque rupture, and are responsible for acute coronary syndromes (ACS). There are limited data regarding the frequency and distribution of TCFA in diseased coronary arteries. Coronary artery OCT was performed in 78 vessels in 47 patients, with stable angina (SA) or ACS. OCT plaque characteristics were derived using criteria that had been validated earlier. TCFA was defined as rich in lipid (two or more quadrants) with thin fibrous cap (<65 μm). Comparison was made between SA and unstable angina, and culprit and nonculprit vessels. There was a higher incidence of TCFA and plaque rupture (65 vs. 24%, P=0.003, and 40 vs. 15%, P=0.04) in ACS patients. This was reflected in a higher lipid pool (2.66 vs. 2.26 quadrants, P=0.04) and minimum fibrous cap thickness (52 vs. 74 μm, P=0.001) in ACS patients. The mean numbers of TCFA (2.5) were similar in patients with SA and ACS. However, the maximal length of TCFA (2.63 vs. 5.54 mm, P=0.026) and plaque rupture sites (P=0.046) were higher in ACS vessels. No relationship was found between baseline characteristics and TCFA incidence and plaque rupture. We identified ACS (P=0.002), higher mean lipid pool (P=0.002), longer TCFA length (P=0.007) and higher number of TCFA (P=0.02) as predictors of plaque rupture sites. In this in-vivo study, we identified a higher incidence of longer TCFAs and plaque rupture sites associated with ACS.

Regulation of heparanase expression in coronary artery disease in diabetic, hyperlipidemic swine

Objective Enzymatic degradation of the extracellular matrix is known to be powerful regulator of atherosclerosis. However, little is known about the enzymatic regulation of heparan sulfate proteoglycans (HSPGs) during the formation and progression of atherosclerotic plaques. Methods and results Swine were rendered diabetic through streptozotocin injection and hyperlipidemic through a high fat diet. Arterial remodeling and local endothelial shear stress (ESS) were assessed using intravascular ultrasound, coronary angiography and computational fluid dynamics at weeks 23 and 30. Coronary arteries were harvested and 142 arterial subsegments were analyzed using histomorphologic staining, immunostaining and real time PCR. Heparanase staining and activity was increased in arterial segments with low ESS, in lesions with thin cap fibroatheroma (TCFA) morphology and in lesions with severely degraded internal elastic laminae. In addition, heparanase staining co-localized with staining for CD45 and MMP-2 within atherosclerotic plaques. Dual staining with gelatinase zymography and heparanase immunohistochemical staining demonstrated co-localization of matrix metalloprotease activity with heparanase staining. A heparanase enzymatic activity assay demonstrated increased activity in TCFA lesions, subsegments with low ESS and in macrophages treated with oxidized LDL or angiotensin II. Conclusions Taken together, our results support a critical role for heparanase in the development of vulnerable plaques and suggest a novel therapeutic target for the treatment of atherosclerosis.

037 In vivo detection of frequency and distribution of thin cap fibroatheroma ANA ruptured plaques in patients with coronary artery disease: a optical coherence tomography study

Objectives The purpose of this study was to assess the prevalence and quantify the Thin- cap fibroatheroma (TCFA) and ruptured plaques in patients with coronary artery disease using optical coherence tomography (OCT). Background TCFA lesions are the most prevalent precursor of plaque rupture, and responsible for acute coronary syndromes. There is limited data regarding the frequency and distribution of TCFA in diseased coronary arteries. Methods Coronary artery OCT was performed in 78 vessels in (47 patients), with stable angina (SA) or acute coronary syndrome (ACS). OCT plaque characteristics were derived using previously validated criteria. TCFA was defined as lipid rich (two or more quadrants) with thin fibrous cap ( Results There was a higher incidence of TCFA and plaque rupture (65% vs 24%, p=0.003, and 40% vs 15%, p=0.04) in ACS patients. This was reflected in higher lipid pool (2.66 vs 2.26 quadrants, p=0.04) and minimum fibrous cap thickness (52 μm vs 74 μm, p=0.001) in ACS patients. The mean numbers of TCFA (2.5) were similar in patients with SA and ACS. However, the maximal length of TCFA (2.63 mm vs 5.54 mm, p=0.026), and plaque rupture sites (p=0.046) were higher in ACS vessels. No relation ship was found between baseline characteristics and TCFA incidences and plaque rupture. We identified ACS (p=0.002), higher mean lipid pool (p=0.002), longer TCFA length (p=0.007), and higher number TCFA (p=0.02) as predictors of plaque rupture sites. Conclusions In this in vivo study, we identified higher incidences of longer length TCFAs and plaque rupture sites associated with ACS.

Intravascular ultrasound radiofrequency analysis of the lesion segment profile in ACS patients

Intravascular ultrasound radiofrequency analysis (IVUS-RF) characterizes plaque components as necrotic core (NC) and dense calcium (DC). The aim of this study was to perform an IVUS-RF derived analysis of the lesion segment profile in acute coronary syndrome (ACS) patients. Therefore, we compared the site of the minimum lumen area--cross sectional area (mla-CSA) with the worst lesion site--CSA (ws-CSA) defined by the maximum NC site. We performed IVUS-RF derived plaque composition and plaque-type classification analysis in 48 ACS patients with 48 culprit (CL) and 69 non-culprit lesions (NCL). The plaque dimension of the mla- and ws-CSA was significantly different regarding the lumen area (5.18 +/- 2.09 mm2 vs. 6.72 +/- 2.73 mm2, p = 0.0013) and the vessel area (14.80 +/- 5.86 mm2 vs. 17.15 +/- 4.94 mm2, p = 0.0142). The absolute plaque composition was also significantly different regarding the DC tissue (0.71 +/- 0.57 mm2 vs. 0.98 +/- 0.54 mm2, p = 0.0102) and the NC tissue (1.41 +/- 1.28 mm2 vs. 1.85 +/- 1.37 mm2, p = 0.0469). The plaque-type classification revealed significantly more thin cap fibroatheroma (TCFA) lesions at the ws-CSA compared to the mla-CSA (n = 53/89.8% vs. n = 26/44.1%, p < 0.0001). In the majority of the CL and NCL lesion segments the ws-CSA was located proximal to the mla-CSA compared to the distal location (n = 65/55.6% vs. n = 23/19.7%). In the majority of the lesion segments in ACS patients the ws-CSA is not identical with the mla-CSA. The ws-CSA compared to mla-CSA presented with significantly more NC and DC tissue resulting in a higher amount of TCFA lesions.