Specific Plaque Characteristics Research Articles

Coronary plaque phenotype associated with positive remodeling

BackgroundPositive remodeling is an integral part of the vascular adaptation process during the development of atherosclerosis, which can be detected by coronary computed tomography angiography (CTA). MethodsA total of 426 patients who underwent both coronary CTA and optical coherence tomography (OCT) were included. Four machine learning (ML) models, gradient boosting machine (GBM), random forest (RF), deep learning (DL), and support vector machine (SVM), were employed to detect specific plaque features. A total of 15 plaque features assessed by OCT were analyzed. The variable importance ranking was used to identify the features most closely associated with positive remodeling. ResultsIn the variable importance ranking, lipid index and maximal calcification arc were consistently ranked high across all four ML models. Lipid index and maximal calcification arc were correlated with positive remodeling, showing pronounced influence at the lower range and diminishing influence at the higher range. Patients with more plaques with positive remodeling throughout their entire coronary trees had higher low-density lipoprotein cholesterol levels and were associated with a higher incidence of cardiovascular events during 5-year follow-up (Hazard ratio 2.10 [1.26–3.48], P ​= ​0.004). ConclusionGreater lipid accumulation and less calcium burden were important features associated with positive remodeling in the coronary arteries. The number of coronary plaques with positive remodeling was associated with a higher incidence of cardiovascular events.

Carotid Plaque Composition and the Importance of Non-Invasive in Imaging Stroke Prevention

Luminal stenosis has been the standard feature for the current management strategies in patients with atherosclerotic carotid disease. Histological and imaging studies show considerable differences between plaques with identical degrees of stenosis. They indicate that specific plaque characteristics like Intraplaque hemorrhage, Lipid Rich Necrotic Core, Plaque Inflammation, Thickness and Ulceration are responsible for the increased risk of ischemic events. Intraplaque hemorrhage is defined by the accumulation of blood components within the plaque, Lipid Rich Necrotic Core is composed of macrophages loaded with lipid, Plaque Inflammation is defined as the process of atherosclerosis itself and Plaque thickness and Ulceration are defined as morphological features. Advances in imaging methods like Magnetic Resonance Imaging, Ultrasound, Computed Tomography and Positron Emission Tomography have enabled a more detailed characterization of the plaque, and its vulnerability is linked to these characteristics, changing the management of these patients based only on the degree of plaque stenosis. Studies like Rotterdam, ARIC, PARISK, CAPIAS and BIOVASC were essential to evaluate and prove the relevance of these characteristics with cerebrovascular symptoms. A better approach for the prevention of stroke is needed. This review summarizes the more frequent carotid plaque features and the available validation from recent studies with the latest evidence.

Identification of Symptomatic Carotid Artery Plaque: A Three-Item Scale Combined Angiography With Optical Coherence Tomography.

Introduction: Symptomatic carotid disease conveys a high risk of recurrent stroke. Plaque morphology and specific plaque characteristics are associated with the risk of stroke. This study aimed to evaluate the detailed plaque features by optical coherence tomography (OCT) and develop a simple scale combining clinical indicators, digital subtraction angiography (DSA), and OCT imaging markers to identify symptomatic carotid plaque.Methods: Carotid plaques from consecutive patients who underwent carotid OCT imaging between June 2017 and June 2021 were evaluated. Clinical characteristics, DSA, and OCT data were compared between the symptomatic and asymptomatic groups. Logistic regression was performed to identify the factors associated with symptomatic carotid plaque and to develop a scale. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the scale.Results: A total of 90 carotid plaques from 90 patients were included (symptomatic 35.6%, asymptomatic 64.4%). Three main factors were found to be associated with symptomatic carotid plaque: high-density lipoprotein cholesterol (HDL-C) <0.925 mmol/L (OR, 4.708; 95% CI, 1.640 to 13.517; P = 0.004), irregular plaque (OR, 4.017; 95% CI, 1.250 to 12.910; P = 0.020), and white thrombus (OR, 4.594; 95% CI, 1.141 to 18.487; P = 0.032). The corresponding score of three items produced a scale with good discrimination (AUC, 0.768; 95% CI, 0.665 to 0.871). The optimal cutoff value of the scale was 1.5 points with 59.4% sensitivity and 84.5% specificity.Conclusion: The three-item scale comprising HDL-C <0.925 mmol/L, angiographical irregular plaque, and white thrombus detected by OCT may provide information to identify symptomatic carotid plaque. Further large-scale studies are required to validate whether the symptomatic carotid plaque scale is clinically valuable in recognizing carotid atherosclerosis in the early stages.

Extracranial Vascular Disease: Carotid Stenosis and Plaque Imaging.

Carotid atherosclerosis is an important contributor to ischemic stroke. When imaging carotid atherosclerosis, it is essential to describe both the degree of luminal stenosis and specific plaque characteristics because both are risk factors for cerebrovascular ischemia. Carotid atherosclerosis can be accurately assessed using multiple imaging techniques, including ultrasonography, computed tomography angiography, and magnetic resonance angiography. By understanding the underlying histopathology, the specific plaque characteristics on each of these imaging modalities can be appreciated. This article briefly describes some of the most commonly encountered plaque features, including plaque calcification, intraplaque hemorrhage, lipid-rich necrotic core, and plaque ulceration.

Optimal Carotid Plaque Features on Computed Tomography Angiography Associated With Ischemic Stroke.

BackgroundStenosis has historically been the major factor used to determine carotid stroke sources. Recent evidence suggests that specific plaque features detected on imaging may be more highly associated with ischemic stroke than stenosis. We sought to determine computed tomography angiography (CTA) imaging features of carotid plaque that optimally discriminate ipsilateral stroke sources.Methods and ResultsIn this institutional review board–approved retrospective cross‐sectional study, 494 ipsilateral carotid CTA‐brain magnetic resonance imaging pairs were available for analysis after excluding patients with alternative stroke sources. Carotid CTA and clinical markers were recorded, a multivariable Poisson regression model was fitted, and backward elimination was performed with a 2‐sided threshold of P<0.10. Discriminatory value was determined using receiver operating characteristic analysis, area under the curve, and bootstrap validation. The final CTA carotid‐source stroke prediction model included intraluminal thrombus (prevalence ratio, 2.8 [P<0.001]; 95% CI, 1.6–4.9), maximum soft plaque thickness (prevalence ratio, 1.2 [P<0.001]; 95% CI, 1.1–1.4), and the rim sign (prevalence ratio, 2.0 [P=0.007]; 95% CI, 1.2–3.3). The final discriminatory value (area under the curve=78.3%) was higher than intraluminal thrombus (56.4%, P<0.001), maximum soft plaque thickness (76.4%, P=0.007), or rim sign alone (69.9%, P=0.001). Furthermore, NASCET (North American Symptomatic Carotid Endarterectomy Trial) stenosis categories (cutoffs of 50% and 70%) had lower stroke discrimination (area under the curve=67.4%, P<0.001).ConclusionsOptimal discrimination of ipsilateral carotid sources of stroke requires information on intraluminal thrombus, maximum soft plaque thickness, and the rim sign. These results argue against the sole use of carotid stenosis to determine stroke sources on CTA, and instead suggest these alternative markers may better diagnose vulnerable carotid plaque and guide treatment decisions.

Carotid artery plaque characteristics: current reporting practices on CT angiography.

Extracranial ICA imaging has largely focused on the degree of luminal stenosis, but recent advances suggest specific plaque features are crucial in stroke risk assessment. We evaluated the current state of reporting carotid plaque features on neck CTAs at an academic institution. In this retrospective observational study, we included neck CTAs performed on patients over age 50 with any reported carotid plaque. We evaluated reports for mention of the following: degree of luminal stenosis, soft plaque, calcified plaque, plaque thickness, quantification of soft and calcified plaque, plaque ulceration, and increased risk associated with specific features. We used Fisher's exact test to compare how often each feature was mentioned. We included a total of 651 reports from unique patients (mean age, 68.1 ± 13.3years). A total of 639 reports (98.1%) explicitly mentioned degree of stenosis per NASCET criteria. Specific plaque features were less frequently characterized: soft plaque in 116 (17.8%); calcified plaque in 166 (25.5%); quantification of the amount of soft plaque and calcified plaque in 24 (3.7%) and 16 (2.5%) reports, respectively; plaque thickness in 12 (1.8%); plaque ulceration in 476 (73.1%); and increased risk associated with plaque in 2 (0.3%). Degree of stenosis was statistically more likely to be mentioned than any other plaque feature (p < 0.001). Currently, nearly all reports mention the degree of luminal stenosis on neck CTAs while a significant minority mention specific plaque features. Despite mounting evidence of the importance of carotid plaque features in stroke risk assessment, radiology reports do not routinely report these findings.

Near infrared spectroscopy and optical coherence tomography derived plaque characteristics associated with increased plaque progression over 12-month follow up

Abstract Background Serial intravascular ultrasound (IVUS) studies demonstrated patterns of either plaque progression, regression or stabilization during pharmacotherapy including statin. At present little is known on specific plaque characteristics that are associated with excessive plaque growth. Purpose To evaluate the utility of near infrared spectroscopy (NIRS) and optical coherence tomography (OCT) to identify characteristics of non-culprit plaques associated with an increase in wall thickness (WT). Methods In this prospective, single-center study, patients with acute coronary syndrome (ACS) underwent, after successful treatment of the culprit lesions, both NIRS-IVUS and OCT assessment of a non-culprit artery at baseline and 12-month follow-up. For each vessel, 1.5-mm segments were identified, matched and divided into 45° sectors. A sector was considered as NIRS positive or labeled as OCT-detected fibrous cap atheroma (FCA), lipid rich or fibrous plaque when &amp;gt;75% of the sector area exhibited NIRS signal or specific OCT-detected feature. The relationship between change in IVUS-based WT, and the presence of NIRS positive signal or OCT-detected plaque components (FCA, lipid rich, fibrous) was evaluated using mixed ANCOVA, with NIRS status and OCT plaque components as fixed factors, and patient as random factor, adjusting for clustering effect of the data. All analyses of plaque WT change were adjusted for baseline WT. To examine the value of NIRS and OCT-detected plaque components in predicting plaque progression, a logistic mixed model was built with plaque progression defined as WT increase &amp;gt;0.2mm over the 12-month follow-up. Results A total of 38 patients (92% male, 21% diabetic) with 9167 matched sectors were analyzed at baseline and 12 months. Mean change in WT between baseline and 12 months was 0.014mm (95% confidence interval [CI] 0.011–0.018, p&amp;lt;0.001). Positive NIRS sectors showed more pronounced plaque progression than NIRS negative sectors (0.057mm, 95% CI 0.032–0.084 vs 0.014mm 95% CI 0.010–0.017, p=0.001) (Figure 1). FCA showed significant progression of WT over the 12-month follow-up (0.104mm, 95% CI 0.007–0.201), whereas a decrease in WT was observed in sectors with fibrous tissue (−0.031mm, 95% CI 0.048–0.014) (p=0.022). Baseline NIRS positive (OR 1.88, 95% CI 1.34–2.64) and OCT-detected lipid rich plaque (OR 1.47, 95% CI 1.20–1.81) were associated with 12-month plaque progression (&amp;gt;0.2mm) by logistic regression. Conclusions Positive NIRS signal and OCT-detected lipid plaque components imaged at baseline in non-culprit coronary arteries of patients presenting with ACS could identify vessel wall regions prone to plaque progression over a 12-month period. Figure 1. Plaque progression and NIRS Funding Acknowledgement Type of funding source: Other. Main funding source(s): M. Tomaniak acknowledges funding received as a Laureate of the European Society of Cardiology Research and Training Programme in the form of the ESC 2018 Grant.

PET/MRI of atherosclerosis

Myocardial infarction and stroke are the most prevalent global causes of death. Each year 15 million people worldwide die due to myocardial infarction or stroke. Rupture of a vulnerable atherosclerotic plaque is the main underlying cause of stroke and myocardial infarction. Key features of a vulnerable plaque are inflammation, a large lipid-rich necrotic core (LRNC) with a thin or ruptured overlying fibrous cap, and intraplaque hemorrhage (IPH). Noninvasive imaging of these features could have a role in risk stratification of myocardial infarction and stroke and can potentially be utilized for treatment guidance and monitoring. The recent development of hybrid PET/MRI combining the superior soft tissue contrast of MRI with the opportunity to visualize specific plaque features using various radioactive tracers, paves the way for comprehensive plaque imaging. In this review, the use of hybrid PET/MRI for atherosclerotic plaque imaging in carotid and coronary arteries is discussed. The pros and cons of different hybrid PET/MRI systems are reviewed. The challenges in the development of PET/MRI and potential solutions are described. An overview of PET and MRI acquisition techniques for imaging of atherosclerosis including motion correction is provided, followed by a summary of vessel wall imaging PET/MRI studies in patients with carotid and coronary artery disease. Finally, the future of imaging of atherosclerosis with PET/MRI is discussed.

Associations Between Features of Nonstenosing Carotid Plaque on Computed Tomographic Angiography and Ischemic Stroke Subtypes.

BackgroundThromboembolism from nonstenosing carotid plaques may be an underrecognized cause of embolic strokes of undetermined source (ESUS). We evaluated the association between features of nonstenosing atherosclerotic plaque on computed tomographic angiography and ESUS.Methods and ResultsWe identified consecutive acute ischemic stroke patients from 2011 to 2015 who had unilateral anterior territory infarction on brain magnetic resonance imaging and a neck computed tomographic angiography. We included ESUS cases and as controls, cardioembolic strokes. Patients with ≥50% internal carotid artery atherosclerotic stenosis ipsilateral to the stroke were excluded from this analysis. Reviewers blinded to infarct location and stroke cause retrospectively evaluated computed tomographic angiography studies for specific plaque features including thickness of the total, soft, and calcified plaque; presence of ulceration; and perivascular fat attenuation. Paired t tests and McNemar's test for paired data were used to compare plaque features ipsilateral versus contralateral to the side of infarction. Ninety‐one patients with ESUS or cardioembolic stroke were included in this study. Total plaque thickness was greater on the infarcted side (2.1±2.0 mm) than the contralateral side (1.2±1.5 mm) (P=0.006) among ESUS cases, but not among cardioembolic cases (1.9±1.6 mm versus 1.8±1.6 mm) (P=0.32).ConclusionsAmong ESUS cases, total plaque thickness was greater ipsilateral to the side of infarction than on the contralateral, stroke‐free side. No such side‐to‐side differences were apparent in cardioembolic strokes. Our findings suggest that nonstenosing large‐artery atherosclerotic plaques represent one underlying mechanism of ESUS.

P870A genetic risk score is associated with increased coronary plaque burden but not specific plaque features: a coronary computed tomography study

Abstract Background Genetic risk scores (GRSs) based on risk variants identified from genome-wide association studies (GWASs) predict coronary artery disease (CAD) risk. However, it is unknown whether the GRS is associated with coronary plaque burden or specific high-risk plaque features responsible for the clinical disease onset. Purpose To investigate if a GRS is associated with coronary plaque burden and specific plaque characteristics, in patients with suspected stable CAD referred for coronary computed tomography angiography (CTA). Methods We consecutively included and genotyped 1645 patients undergoing coronary CTA. Using LDPred, a previously validated GRS was calculated as the weighted sum of the number of CAD risk variants identified from the CARDIoGRAMplusC4D GWAS meta-analysis. Plaques were evaluated using an 18-segment model and characterized by stenosis severity (0%, 1–49%, 50–69%, 70–100%) and composition (calcified (&gt;80% calcified), mixed-calcified (50–80% calcified), mixed-soft (20–50% calcified), or soft (&lt;20% calcified)). The segment stenosis score and the coronary artery calcium score (CACS) were used as measures of plaque burden. Multivariate regression models were used to assess the effect per standard deviation (SD) of the GRS with adjustment for age, sex, hypertension, hypercholesterolemia, BMI, chest pain symptoms, and active smoking. Results For each SD increase in the GRS, the segment stenosis score increased with 49% (p=8.6e-27) and CACS increased with 110% (p=2.3e-24). The GRS was associated with a higher risk of plaque stenosis &gt;50% (OR: 1.74, p=3.2e-15), calcified (OR: 1.65, p=3.0e-16), mixed-calcified (OR: 1.64, p=1.5e-8), mixed-soft (OR: 1.44, p=1.6e-6), and soft plaques (OR: 1.40, p=3.0e-6), and all coronary vessels were more often affected with plaques (all p-values &lt;1.0e-4). When analyzing the plaque characteristics (3007 plaques in 849 patients), the GRS was associated with stenosis severity (OR per severity category: 1.15 (p=0.005), but not with extent of calcification, proximal location, or presence in any of the major coronary vessels (all p-values &gt;0.05). GRS and Plaque burden Conclusion The GRS was strongly associated with the extent and severity of CAD at coronary CTA, but not any specific plaque characteristics per se. The results may suggest that polygenic risk based on large CAD-GWAS increases CAD risk through increased coronary plaque burden rather than specific plaque features.

P6184Association of coronary plaque characteristics and the translesional gradient by FFRct in asymptomatic patients with newly diagnosed type-2 diabetes mellitus

Abstract Background Coronary CT angiography (CCTA) derived fractional flow reserve (FFRct) is increasingly for decision-making in patients with stable chest pain. The relation between vessel specific plaque characteristics and the translesional gradient by FFRct in patients with type-2 diabetes mellitus (T2DM) is not fully explored. Purpose To examine the association between vessel specific plaque characteristics as determined by CCTA and the translesional gradient as assessed by FFRct in asymptomatic patients with newly diagnosed T2DM. Methods Total plaque volume and the volumes of calcified plaque (CP), low-density noncalcified plaque (LD-NCP) and non-LD-NCP were assessed on a per-vessel basis by quantitative plaque analysis using Autoplaque. Irregularities of the vessel wall giving a vessel-specific total plaque volume &lt;50 mm3 were excluded from the analyses. Positive remodeling was defined by a remodeling index &gt;1.1. Spotty calcification was defined as calcifications comprising &lt;90° of the vessel circumference and &lt;3 mm length. FFRct-analysis was performed from standard acquired CCTA data sets by HeartFlow. Any FFRct-value in the major coronary arteries &gt;1.8 mm in diameter was registered. The translesional gradient, defined as the difference of FFRct-values immediately proximal and distal to lesion, was calculated in most severe lesion per-vessel. Lesions were categorized according to a ΔFFRct threshold of 0.06. Plaque analysis and comparison to ΔFFRct were performed by staff blinded to patient data. Results A total of 76 patients; age, mean (SD): 56 (11) years; males, n (%): 49 (65), with newly diagnosed (&lt;1 year) T2DM were studied. Haemoglobin A1c, median (IQR) was 45 mmol/L (42–50). Risk factors, mean (SD) were as follows: total-cholesterol, 4.4 mmol/L (1.0); LDL-cholesterol, 2.5 mmol/L (0.8); systolic blood pressure, 131 mmHg (12). In the analysis 57 vessels in 30 patients were included, while 24 vessels were classified as having irregularities. ΔFFRct ≥0.06 was registered in 22 (39%) plaques. Vessel specific plaque volumes (mm3), ΔFFRct ≥0.06 vs. ΔFFRct &lt;0.06, were, median (IQR): LD-NCP, 28.1 (9.5–62.3) vs. 18.3 (10.2–27.5); non-LD-NCP, 129.5 (74.1–186.8) vs. 98.1 (65.7–142.1); total plaque volume, 209.4 (137.1–359.3) vs. 139.6 (108.3–220.0), all p&gt;0.05. The vessel-specific CP volume, median (IQR), was higher in vessels with ΔFFRct ≥0.06 vs. ΔFFRct &lt;0.06: 51.9 (20.5–85.4) vs. 13.5 (4.1–68.5), p=0.015. Adverse plaque characteristics ΔFFRct ≥0.06 vs. ΔFFRct &lt;0.06, were, n (%): positive remodeling, 21 (95%) vs. 34 (97%) and spotty calcification, 9 (41%) vs. 14 (40%). The relative distribution of vessel specific plaque components according to ΔFFRct is illustrated in the Figure. Conclusion In asymptomatic patients with newly diagnosed and well-controlled T2DM, the occurrence of high-risk coronary plaque features was frequently observed. The applied translesional gradient by FFRct was not predictive of adverse coronary plaque characteristics. Acknowledgement/Funding The Danish Diabetes Academy supported by the Novo Nordisk Foundation; University of Southern DenmarkCenter Southwest, Denmark

Detection of Vulnerable Plaque in Patients with Cryptogenic Stroke.

In up to 40% of ischemic stroke cases the etiology remains unknown. A substantial proportion of these patients has non- or only mildly stenosing carotid artery plaques not fulfilling common criteria for large artery stroke, but beeing suspicious for arterio-arteriell embolism. Several imaging techniques allow the non-invasive analysis of plaque features. Nevertheless, carotid MRI might be best suited to assess the key features of vulnerable plaques. This review article discusses potential causes of cryptogenic stroke, the role of plaque imaging in non-stenosing plaques and the association of vulnerable plaques and specific plaque features with stroke risk and stroke recurrence.

Deficiency of the stroke relevant HDAC9 gene attenuates atherosclerosis in accord with allele-specific effects at 7p21.1.

Recent genome-wide association studies identified the histone deacetylase 9 (HDAC9) gene region as a major risk locus for large-vessel stroke and coronary artery disease. However, the mechanisms linking variants at this locus to vascular risk are poorly understood. In this study, we investigated the candidacy and directionality of HDAC9 in atherosclerosis and analyzed associations between risk alleles at 7p21.1 and plaque characteristics. Allele-dependent expression of HDAC9 was analyzed in human peripheral blood mononuclear cells of healthy donors. Effects of HDAC9 deficiency on atherosclerotic plaques were investigated in 18- and 28-week-old ApoE(-/-) mice by histology and immunohistochemistry. We further performed detailed plaque phenotyping and genotyping of rs2107595, the lead single-nucleotide polymorphism for large-vessel stroke, in carotid endarterectomy samples of 1858 subjects from the Athero-Express study. Gene expression studies in peripheral blood mononuclear cells revealed increased mRNA levels of HDAC9 but not of neighboring genes (TWIST1/FERD3L) in risk allele carriers of rs2107595. Compared with HDAC9(+/+)ApoE(-/-) mice, HDAC9(-/-)ApoE(-/-) mice exhibited markedly reduced lesion sizes throughout atherosclerotic aortas and significantly less advanced lesions. The proportion of Mac3-positive macrophages was higher in plaques from HDAC9(-/-)ApoE(-/-) mice, but this was largely because of a lower proportion of advanced lesions. Analysis of human atherosclerotic plaques revealed no association between rs2107595 and specific plaque characteristics. Our results suggest that HDAC9 represents the disease-relevant gene at the stroke and coronary artery disease risk locus on 7p21.1, and that risk alleles in this region mediate their effects through increased HDAC9 expression. Targeted inhibition of HDAC9 might be a viable strategy to prevent atherosclerosis.

A Systematic Literature Review of Ultrasonography for Morphology and Characterization of Vulnerable Carotid Artery Plaques

Background and Purpose Although ultrasound (US) evaluation of the carotid artery for stenosis is the accepted method for identifying risk factors for cerebrovascular (CV) events, patients with specific plaque morphology may be at increased risk. Plaque characterization via US is a potentially useful adjunct to stenotic grading for identifying vulnerable carotid disease. The aim of this study was to systematically review published clinical trials via the use of US to identify vulnerable plaques among both symptomatic and asymptomatic plaques. Methods We used a systematic search using Medline, Embase, and the Cochrane library databases to find relevant studies published between 2001 and 2011. We reviewed randomized, controlled human clinical trials that validated the applicability, diagnostic accuracy, and diagnostic impact of US carotid plaque characterization. For studies reporting qualitative findings, we abstracted information about the study design and technique and the quality of the methodology and analyzed the data using a modified Jadad scale. Results In this review, we identified 12 studies related to the evaluation of carotid plaque using US. The studies used a wide range of methodologies to quantify and image the plaque morphology. Published literature on this subject is lacking; however, this deficit may be because current studies are ongoing. Specific plaque characteristics identified as vulnerable included particular echo texture, the presence of echolucency and/or ulceration, surface alterations, and volume assessment using 3-dimensional US (3D US). In a minority of studies investigators used histopathology as the reference standard, and in most they used subsequent clinical observations. All studies demonstrated that US has good accuracy and specificity in identifying possible imaging characteristics related to vulnerable plaques. Conclusion The collected evidence shows that US is effectively able to detect specific carotid plaque characteristics related to high-risk plaques vulnerable for CV events. We anticipate that additional well-designed prospective studies will provide more definitive evidence and distinguish specific distinctive findings that may serve as indicators of vulnerable plaques. Our findings must be extended to demonstrate the accuracy and validity in everyday clinical imaging findings.

Novel Functional Risk Factors for the Prediction of Cardiovascular Events in Vulnerable Patients Following Acute Coronary Syndrome

Over the years there has been considerable improvement in the clinical outcomes of patients treated for acute coronary syndrome (ACS). Despite a significant reduction in acute mortality, a large percentage of patients post ACS continue to experience adverse cardiovascular (CV) events, with high long-term mortality rates and overall suboptimal medical management. Long-term risk prediction tools rely on traditional CV risk factors and are developed and validated in specific populations. Established CV risk factors, however, only explain half or fewer of CV events. These risk models may thus not be optimal in determining individual risk for long-term adverse outcomes or in helping to identify individual patients who do not respond to therapy. Identifying the specific plaque characteristics associated with increased likelihood for thrombotic complications and rapid progression has led to the concept of the vulnerable plaque. Recently, "vulnerable myocardium" (ie, myocardium that is prone to myocardial ischemia and fatal arrhythmia) has been shown to play an important role in outcome. Both vulnerable plaque and vulnerable myocardium are associated with functional vascular abnormalities, such as endothelial dysfunction, which are considered a key event in the initiation, progression and complications of coronary artery disease. Endothelial dysfunction may serve as an underlying unifying mechanism that would independently predict long-term outcome in patients with ACS undergoing revascularization.

Invasive imaging technologies

Since the introduction of intravascular, catheter-based invasive imaging and diagnostic tools in the catheterization laboratories two decades ago, the functional assessment of angiographically moderate or ambiguous lesions by fractional flow reserve measurements represents the established standard of care today. Likewise, intravascular ultrasound (IVUS) is widely accepted to guide treatment strategy in complex lesions, such as long or left main stem lesions. Developments are driven by the clinical interest to optimize treatment, prevent periprocedural complications, understand treatment failure and understand progression of atherosclerosis. As a result, a variety of devices are now clinically available that enable detection and monitoring of specific plaque features over time, such as the presence of necrotic core by IVUS-VH, a lipid-core plaque by near infrared (NIR) spectroscopy or a thin fibrous cap atheroma by optical coherence tomography (OCT). As the physical boundaries for both light and sound are different, these imaging technologies offer different advantages and limitations. Light-based technologies offer unparalleled high image resolution (OCT) or unparalleled high sensitivity and specificity for distinct plaque components (NIR spectroscopy), whereas conventional IVUS offers a much better tissue penetration. From a clinical perspective, both types of information are valuable. Ideally, this information should easily and in real time be available in the catheterization laboratory, consisting of co-registered datasets gained during a single catheter pullback. On this background, a combined NIR spectroscopy and IVUS catheter has recently been introduced for clinical use. The article discusses the potential and limitations of these different technologies. They may allow advanced coronary plaque diagnosis in a fast, accurate, reliable, user- and patient-friendly manner and, as such, can help to improve clinical practice today and therapeutic options in the future.

Carotid MRI: a tool for monitoring individual response to cardiovascular therapy?

Stroke remains a leading cause of morbidity and mortality. While stroke-related mortality has declined over the past four decades, data indicate that the mortality rate has begun to plateau. This change in trend may be attributable to variation in individual response to therapies that were derived from population-based studies. Further reductions in stroke mortality may require individualized care governed by directly monitoring the effects of cardiovascular therapy. In this article, carotid MRI is considered as a tool for monitoring in vivo carotid atherosclerotic disease, a principal etiology of stroke. Carotid MRI has been previously utilized to identify specific plaque features beyond luminal stenosis that are predictive of transient ischemic attack and stroke. To gain perspective on the possibility of monitoring plaque change within the individual, clinical trials and natural history studies that have used serial carotid MRI are considered. Data from these studies indicate that patients with a lipid-rich necrotic core with or without intraplaque hemorrhage may represent the desired phenotype for monitoring treatment effects in the individual. Advances in tissue-specific sequences, acquisition resolution, scan time, and techniques for monitoring inflammation and mechanical forces are expected to enable earlier detection of response to therapy. In so doing, cost-effective multicenter studies can be conducted to confirm the anticipated positive effects on outcomes of using carotid MRI for individualized care in patients with carotid atherosclerosis. In accordance, carotid MRI is poised to emerge as a powerful clinical tool for individualized management of carotid atherosclerotic disease to prevent stroke.

MR Carotid Plaque Imaging and Contrast-Enhanced MR Angiography Identifies Lesions Associated with Recent Ipsilateral Thromboembolic Symptoms: An In Vivo Study at 3T

Recent research has suggested the importance of plaque composition to identify patients at risk for stroke. This study aims to identify specific plaque features on 3T carotid MR imaging and CE-MRA associated with recent carotid thromboembolic symptoms in patients with mild/moderate versus severe stenosis. Ninety-seven consecutive patients (symptomatic, 13; asymptomatic, 84) with 50%-99% stenosis by sonography or CT angiography underwent carotid plaque imaging combined with MRA at 3T. The symptomatic carotid artery or the most stenotic asymptomatic carotid artery was chosen as the index vessel to be analyzed. Plaque features were compared by symptomatic status in patients with mild/moderate (30%-70%) versus severe (70%-99%) stenosis on MRA. Ninety (92.8%) patients had sufficient image quality for interpretation. In 50 patients with mild/moderate stenosis, there were significant associations between the presence of the following plaque characteristics and symptoms: thin/ruptured fibrous cap (100% versus 36%, P = .006) and lipid-rich necrotic core (100% versus 39%, P = .022), with marginal association with hemorrhage (86% versus 33%, P = .055). In 40 patients with severe stenosis, only the angiographic presence of ulceration (86% versus 36%, P = .039) was associated with symptoms. Several plaque components identified on 3T MR imaging are correlated with recent ipsilateral carotid thromboembolic symptoms. These preliminary results also suggest that associations between plaque characteristics and symptom history may vary by degree of stenosis. If confirmed in larger studies, carotid MR imaging may distinguish stable from unstable lesions, particularly in individuals with mild/moderate stenosis in whom the role of surgical intervention is currently unclear.

Histopathology of Carotid Atherosclerotic Disease

Stroke is the third leading cause of death in the United States, constituting approximately 700,000 cases each year, of which about 500,000 are first attacks and 200,000 are recurrent attacks. Ischemic stroke accounts for the majority of all strokes (88%), followed by intracerebral hemorrhage (9%) and subarachnoid hemorrhage (3%). Patients with substantial carotid narrowing are at increased risk for major stroke; however, recent studies suggest that factors other than the degree of carotid stenosis are involved in ischemic stroke pathogenesis. Atherosclerotic plaque of the stenotic carotid artery is the underlying cause of the majority of ischemic strokes and specific plaque characteristics have been associated with ischemic brain injury. Several studies have demonstrated that the mechanisms of plaque instability in the carotid circulation are similar to those in the coronary circulation. The purpose of this review is to characterize atherosclerotic carotid disease in light of our knowledge of coronary atherosclerosis and relate carotid plaque morphology to cerebral ischemic syndromes. Histological examination of the carotid plaque specimen should provide insights into the underlying plaque morphology that is responsible for the disease and should help determine the potential treatments that are likely to be beneficial in the prevention of a subsequent event.

Carotid plaque morphology and clinical events.

Studies have suggested that B-mode ultrasonography can be used to determine carotid plaque composition and that specific plaque characteristics are associated with a worse clinical outcome. However, histological studies examining the relationship between carotid plaque morphology and clinical outcome have reported conflicting findings. Furthermore, few investigators have described plaque morphology in quantifiable terms. This study examines the association between the volume of carotid plaque constituents and preoperative ischemic neurological symptoms. Constituents examined were chosen based on their potential for identification by current diagnostic imaging modalities such as ultrasound or MRI. Atherosclerotic plaques from 43 patients undergoing carotid endarterectomy were examined histologically, with sections obtained every 0.5 to 1 mm. The lesions were examined for the presence and quantity of fibrous intimal tissue, intraplaque hemorrhage, lipid core, necrotic plaque core, and calcification. The quantity of each constituent was compared in plaques removed from symptomatic patients with those excised from asymptomatic individuals. Differences were analyzed with a Kolmogorov-Smirnov statistic. There was no difference between plaques removed from asymptomatic and symptomatic patients with regard to the presence and volume of fibrous intimal tissue, intraplaque hemorrhage, the lipid core, the necrotic core, or calcification. In patients with highly stenotic carotid lesions who are undergoing carotid endarterectomy, gross plaque composition is similar regardless of preoperative symptom status. Given this similarity, it is unlikely that differences in the volume of intraplaque hemorrhage, lipid core, necrotic core, or calcification in atherosclerotic carotid plaques explain their embolic history.