Anna Zavodni

The Value of Carotid Artery Plaque and Intima-Media Thickness for Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis

Background Carotid artery plaques are associated with coronary artery atherosclerotic lesions. We evaluated various ultrasound definitions of carotid artery plaque as predictors of future cardiovascular disease (CVD) and coronary heart disease (CHD) events. Methods and Results We studied the risk factors and ultrasound measurements of the carotid arteries at baseline of 6562 members (mean age 61.1 years; 52.6% women) of the Multi‐Ethnic Study of Atherosclerosis (MESA). ICA lesions were defined subjectively as >0% or ≥25% diameter narrowing, as continuous intima‐media thickness (IMT) measurements (maximum IMT or the mean of the maximum IMT of 6 images) and using a 1.5‐mm IMT cut point. Multivariable Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CHD, and stroke. Harrells C‐statistics, Net Reclassification Improvement, and Integrated Discrimination Improvement were used to evaluate the incremental predictive value of plaque metrics. At 7.8‐year mean follow‐up, all plaque metrics significantly predicted CVD events (n=515) when added to Framingham risk factors. All except 1 metric improved the prediction of CHD (by C‐statistic, Net Reclassification Improvement, and Integrated Discrimination Improvement. Mean of the maximum IMT had the highest NRI (7.0%; P=0.0003) with risk ratio of 1.43/mm; 95% CI 1.26–1.63) followed by maximum IMT with an NRI of 6.8% and risk ratio of 1.27 (95% CI 1.18–1.38). Conclusion Ultrasound‐derived plaque metrics independently predict cardiovascular events in our cohort and improve risk prediction for CHD events when added to Framingham risk factors.

T1 mapping of the myocardium: Intra-individual assessment of the effect of field strength, cardiac cycle and variation by myocardial region

BackgroundMyocardial T1 relaxation time (T1 time) and extracellular volume fraction (ECV) are altered in the presence of myocardial fibrosis. The purpose of this study was to evaluate acquisition factors that may result in variation of measured T1 time and ECV including magnetic field strength, cardiac phase and myocardial region.Methods31 study subjects were enrolled and underwent one cardiovascular MR exam at 1.5 T and two exams at 3 T, each on separate days. A Modified Look-Locker Inversion Recovery (MOLLI) sequence was acquired before and 5, 10, 12, 20, 25 and 30 min after administration of 0.15 mmol/kg gadopentetate dimeglumine (Gd-DTPA; Magnevist) at 1.5 T (exam 1). For exam 2, MOLLI sequences were acquired at 3 T both during diastole and systole, before and after administration of Gd-DTPA (0.15 mmol/kg Magnevist).Exam 3 was identical to exam 2 except gadobenate dimeglumine was administered (Gd-BOPTA; 0.1 mmol/kg Multihance). T1 times were measured in myocardium and blood. ECV was calculated by (ΔR1myocardium/ΔR1blood)*(1-hematocrit).ResultsBefore gadolinium, T1 times of myocardium and blood were significantly greater at 3 T versus 1.5 T (28% and 31% greater, respectively, p < 0.001); after gadolinium, 3 T values remained greater than those at 1.5 T (14% and 12% greater for myocardium and blood at 3 T with Gd-DTPA, respectively, p < 0.0001 and 18% and 15% greater at 3 T with Gd-BOPTA, respectively, p < 0.0001). However, ECV did not vary significantly with field strength when using the same contrast agent at equimolar dose (p = 0.2). Myocardial T1 time was 1% shorter at systole compared to diastole pre-contrast and 2% shorter at diastole compared to systole post-contrast (p < 0.01). ECV values were greater during diastole compared to systole on average by 0.01 (p < 0.01 to p < 0.0001). ECV was significantly higher for the septum compared to the non-septal myocardium for all three exams (p < 0.0001-0.01) with mean absolute differences of 0.01, 0.004, and 0.07, respectively, for exams 1, 2 and 3.ConclusionECV is similar at field strengths of 1.5 T and 3 T. Due to minor variations in T1 time and ECV during the cardiac cycle and in different myocardial regions, T1 measurements should be obtained at the same cardiac phase and myocardial region in order to obtain consistent results.

T1 mapping of the myocardium: intra-individual assessment of post-contrast T1 time evolution and extracellular volume fraction at 3T for Gd-DTPA and Gd-BOPTA.

PurposeMyocardial T1 relaxation time (T1 time) and extracellular volume fraction (ECV) are altered in patients with diffuse myocardial fibrosis. The purpose of this study was to perform an intra-individual assessment of normal T1 time and ECV for two different contrast agents.MethodsA modified Look-Locker Inversion Recovery (MOLLI) sequence was acquired at 3 T in 24 healthy subjects (8 men; 28 ± 6 years) at mid-ventricular short axis pre-contrast and every 5 min between 5-45 min after injection of a bolus of 0.15 mmol/kg gadopentetate dimeglumine (Gd-DTPA; Magnevist®) (exam 1) and 0.1 mmol/kg gadobenate dimeglumine (Gd-BOPTA; Multihance®) (exam 2) during two separate scanning sessions. T1 times were measured in myocardium and blood on generated T1 maps. ECVs were calculated as ΔR1myocardium/ΔR1blood*1−hematocrit.ResultsMean pre-contrast T1 relaxation times for myocardium and blood were similar for both the first and second CMR exam (p > 0.5). Overall mean post-contrast myocardial T1 time was 15 ± 2 ms (2.5 ± 0.7%) shorter for Gd-DTPA at 0.15 mmol/kg compared to Gd-BOPTA at 0.1 mmol/kg (p < 0.01) while there was no significant difference for T1 time of blood pool (p > 0.05). Between 5 and 45 minutes after contrast injection, mean ECV values increased linearly with time for both contrast agents from 0.27 ± 0.03 to 0.30 ± 0.03 (p < 0.0001). Mean ECV values were slightly higher (by 0.01, p < 0.05) for Gd-DTPA compared to Gd-BOPTA. Inter-individual variation of ECV was higher (CV 8.7% [exam 1, Gd-DTPA] and 9.4% [exam 2, Gd-BOPTA], respectively) compared to variation of pre-contrast myocardial T1 relaxation time (CV 4.5% [exam 1] and 3.0% [exam 2], respectively). ECV with Gd-DTPA was highly correlated to ECV by Gd-BOPTA (r = 0.803; p < 0.0001).ConclusionIn comparison to pre-contrast myocardial T1 relaxation time, variation in ECV values of normal subjects is larger. However, absolute differences in ECV between Gd-DTPA and Gd-BOPTA were small and rank correlation was high. There is a small and linear increase in ECV over time, therefore ideally images should be acquired at the same delay after contrast injection.

Interstitial Myocardial Fibrosis Assessed as Extracellular Volume Fraction with Low-Radiation-Dose Cardiac CT

PURPOSE To develop a cardiac computed tomographic (CT) method with which to determine extracellular volume (ECV) fraction, with cardiac magnetic resonance (MR) imaging as the reference standard. MATERIALS AND METHODS Study participants provided written informed consent to participate in this institutional review board-approved study. ECV was measured in healthy subjects and patients with heart failure by using cardiac CT and cardiac MR imaging. Paired Student t test, linear regression analysis, and Pearson correlation analysis were used to determine the relationship between cardiac CT and MR imaging ECV values and clinical parameters. RESULTS Twenty-four subjects were studied. There was good correlation between myocardial ECV measured at cardiac MR imaging and that measured at cardiac CT (r = 0.82, P < .001). As expected, ECV was higher in patients with heart failure than in healthy control subjects for both cardiac CT and cardiac MR imaging (P = .03, respectively). For both cardiac MR imaging and cardiac CT, ECV was positively associated with end diastolic and end systolic volume and inversely related to ejection fraction (P < .05 for all). Mean radiation dose was 1.98 mSv ± 0.16 (standard deviation) for each cardiac CT acquisition. CONCLUSION ECV at cardiac CT and that at cardiac MR imaging showed good correlation, suggesting the potential for myocardial tissue characterization with cardiac CT.

Carotid Artery Plaque Morphology and Composition in Relation to Incident Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis (MESA)

PURPOSE To determine if carotid plaque morphology and composition with magnetic resonance (MR) imaging can be used to identify asymptomatic subjects at risk for cardiovascular events. MATERIALS AND METHODS Institutional review boards at each site approved the study, and all sites were Health Insurance Portability and Accountability Act (HIPAA) compliant. A total of 946 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated with MR imaging and ultrasonography (US). MR imaging was used to define carotid plaque composition and remodeling index (wall area divided by the sum of wall area and lumen area), while US was used to assess carotid wall thickness. Incident cardiovascular events, including myocardial infarction, resuscitated cardiac arrest, angina, stroke, and death, were ascertained for an average of 5.5 years. Multivariable Cox proportional hazards models, C statistics, and net reclassification improvement (NRI) for event prediction were determined. RESULTS Cardiovascular events occurred in 59 (6%) of participants. Carotid IMT as well as MR imaging remodeling index, lipid core, and calcium in the internal carotid artery were significant predictors of events in univariate analysis (P < .001 for all). For traditional risk factors, the C statistic for event prediction was 0.696. For MR imaging remodeling index and lipid core, the C statistic was 0.734 and the NRI was 7.4% and 15.8% for participants with and those without cardiovascular events, respectively (P = .02). The NRI for US IMT in addition to traditional risk factors was not significant. CONCLUSION The identification of vulnerable plaque characteristics with MR imaging aids in cardiovascular disease prediction and improves the reclassification of baseline cardiovascular risk.

Assessment of Atherosclerosis in Chronic Granulomatous Disease

Background— Patients with chronic granulomatous disease (CGD) experience immunodeficiency because of defects in the phagocyte NADPH oxidase and the concomitant reduction in reactive oxygen intermediates. This may result in a reduction in atherosclerotic injury. Methods and Results— We prospectively assessed the prevalence of cardiovascular risk factors, biomarkers of inflammation and neutrophil activation, and the presence of magnetic resonance imaging and computed tomography quantified subclinical atherosclerosis in the carotid and coronary arteries of 41 patients with CGD and 25 healthy controls in the same age range. Univariable and multivariable associations among risk factors, inflammatory markers, and atherosclerosis burden were assessed. Patients with CGD had significant elevations in traditional risk factors and inflammatory markers compared with control subjects, including hypertension, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, and low high-density lipoprotein. Despite this, patients with CGD had a 22% lower internal carotid artery wall volume compared with control subjects (361.3±76.4 mm3 versus 463.5±104.7 mm3; P<0.001). This difference was comparable in p47phox- and gp91phox-deficient subtypes of CGD and independent of risk factors in multivariate regression analysis. In contrast, the prevalence of coronary arterial calcification was similar between patients with CGD and control subjects (14.6%, CGD; 6.3%, controls; P=0.39). Conclusions— The observation by magnetic resonance imaging and computerized tomography of reduced carotid but not coronary artery atherosclerosis in patients with CGD despite the high prevalence of traditional risk factors raises questions about the role of NADPH oxidase in the pathogenesis of clinically significant atherosclerosis. Additional high-resolution studies in multiple vascular beds are required to address the therapeutic potential of NADPH oxidase inhibition in cardiovascular diseases. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01063309.

Coronary artery calcium is associated with degree of stenosis and surface irregularity of carotid artery

OBJECTIVES Carotid stenosis and plaque stability are critical determinants of risk for ischemic stroke. The aim of this study is to elucidate the association of CAC with carotid stenosis and plaque characteristics. METHODS We examined data from the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of subclinical cardiovascular disease in multiethnic participants (N = 6814). The association between CAC measured by computed tomography and carotid ultrasonography of carotid plaque was examined using multiple logistic linear models adjusting for traditional vascular risk factors including ethnicity. We also developed ethnic specific models to compare the relationship between CAC and carotid disease across the four ethnicities. RESULTS Significant carotid stenosis was associated with the presence of CAC (OR 1.73; 95% CI, 1.20-2.49) and log-transformed Agatston score (OR per 1 point increase, 1.18; 95% CI 1.04-1.35). Overt carotid stenosis was also associated with the presence of CAC (OR, 2.34; 95% CI, 1.93-2.83) and log-transformed Agatston score (OR per 1 point increase, 1.53; 95% CI 1.38-1.69). Irregular plaque surface was associated with the presence of CAC (OR, 1.87; 95% CI 1.50-2.32) and the log-transformed Agatston score (OR per 1 point 1 increase, 1.31; 95% CI 1.16-1.48). Associations between CAC and stenosis/stability were not different across ethnicities. CONCLUSIONS Both the presence of CAC and log-transferred Agatston score are independently associated with significant/overt carotid stenosis and carotid plaque surface irregularity regardless of ethnicity. The subjects with a positive or increased CAC score are more likely to have carotid disease potentially increasing their risk for future ischemic stroke.

Advanced MRI for carotid plaque imaging

Abstract Atherosclerosis is the ubiquitous underling pathological process that manifests in heart attack and stroke, cumulating in the death of one in three North American adults. High-resolution magnetic resonance imaging (MRI) is able to delineate atherosclerotic plaque components and total plaque burden within the carotid arteries. Using dedicated hardware, high resolution images can be obtained. Combining pre- and post-contrast T1, T2, proton-density, and magnetization-prepared rapid acquisition gradient echo weighted fat-saturation imaging, plaque components can be defined. Post-processing software allows for semi- and fully automated quantitative analysis. Imaging correlation with surgical specimens suggests that this technique accurately differentiates plaque features. Total plaque burden and specific plaque components such as a thin fibrous cap, large fatty or necrotic core and intraplaque hemorrhage are accepted markers of neuroischemic events. Given the systemic nature of atherosclerosis, emerging science suggests that the presence of carotid plaque is also an indicator of coronary artery plaque burden, although the preliminary data primarily involves patients with stable coronary disease. While the availability and cost-effectiveness of MRI will ultimately be important determinants of whether carotid MRI is adopted clinically in cardiovascular risk assessment, the high accuracy and reliability of this technique suggests that it has potential as an imaging biomarker of future risk.

Cardiac magnetic resonance imaging and its electrocardiographs (ECG): tips and tricks

All cardiac magnetic resonance (CMR) techniques aim to create still depictions of a dynamic and ever-adapting organ. Most CMR methods rely on cardiac gating to capture information during fleeting periods of relative cardiac quiescence, at end diastole or end systole, or to acquire partial images throughout the cardiac cycle and average these signals over several heart beats. Since the inception of clinical CMR in the early 1980s, priority has been given to improving methods for image gating. The aim of this work is to provide a basic understanding of the ECG acquisition, demonstrate common ECG-related artifacts and to provide practical methods for overcoming these issues. Meticulous ECG preparation is essential for optimal CMR acquisition and these techniques must be adaptable to the individual patient.

Magnetic Resonance Imaging of Carotid Atherosclerosis and the Risk of Stroke

Stroke attributable to carotid atherosclerosis is a leading cause of mortality and morbidity. The clinical management of carotid atherosclerosis presently relies on the degree of stenosis determined by angiography. Degree of stenosis is limited in stratifying patients’ risk of stroke. Advances in magnetic resonance imaging have resulted in the ability to directly assess atherosclerotic plaque components, morphology, and biomechanical stress levels. Components of atherosclerosis, including lipid-rich necrotic core, fibrous cap thickness/disruption, and intraplaque hemorrhage, are promising emerging indicators of stroke. Information beyond luminal stenosis from magnetic resonance imaging may allow for improved detection of patients at risk of stroke from carotid atherosclerosis. We review the recent literature on the relationship of magnetic resonance imaging detected plaque components and cerebrovascular events. Clinical applications of magnetic resonance imaging of carotid plaque components are discussed.