New Applications in Echocardiography for Ultrasound Contrast Agents in the 21st Century.

Contrast echocardiography microbubbles are ultrasound-enhancing agents that were originally designed to help improve endocardial border definition, known as left ventricle opacification, and to enhance Doppler signals. Over time, contrast microbubbles are used to assess myocardial perfusion because they travel through the capillaries of the cardiac circulation. Current research provides good evidence that myocardial perfusion echocardiography improves comprehensive echocardiographic evaluations of ischemic heart disease. The approval of regulatory authorities and the availability of quantitative operator-independent analysis software will hopefully prompt physicians and sonographers to implement myocardial perfusion echocardiography into the daily workflow of echo laboratories. New diagnostic and therapeutic applications will result in improved patient care, especially in the area of sonothrombolysis, where preliminary data have already shown utilization in ST elevation myocardial infarction, improving left ventricular systolic function and reducing the need for implantable defibrillators at 6-mo follow-up. This review gives an overview of the applications of myocardial perfusion imaging with ultrasound. Each cited study had institutional review board/institutional animal care and use approval.

Reciprocal Multifaceted Interaction Between HDL (High-Density Lipoprotein) and Myocardial Infarction.

Despite decades of therapeutic advances, myocardial infarction remains a leading cause of death worldwide. Recent studies have identified HDLs (high-density lipoproteins) as a potential candidate for mitigating coronary ischemia/reperfusion injury via a broad spectrum of signaling pathways. HDL ligands, such as S1P (sphingosine-1-phosphate), Apo (apolipoprotein) A-I, clusterin, and miRNA, may influence the opening of the mitochondrial channel, insulin sensitivity, and production of vascular autacoids, such as NO, prostacyclin, and endothelin-1. In parallel, antioxidant activity and sequestration of oxidized molecules provided by HDL can attenuate the oxidative stress that triggers ischemia/reperfusion. Nevertheless, during myocardial infarction, oxidation and the capture of oxidized and proinflammatory molecules generate large phenotypic and functional changes in HDL, potentially limiting its beneficial properties. In this review, new findings from cellular and animal models, as well as from clinical studies, will be discussed to describe the cardioprotective benefits of HDL on myocardial infarction. Furthermore, mechanisms by which HDL modulates cardiac function and potential strategies to mitigate postmyocardial infarction risk damage by HDL will be detailed throughout the review.

HDL-Targeted Therapies During Myocardial Infarction.

It is now apparent that a variety of deleterious mechanisms intrinsic to myocardial infarction (MI) exists and underlies its high residual lethality. Indeed, despite effective coronary patency therapies, ischemia and reperfusion (I/R) injury accounts for about 50% of the infarcted mass. In this context, recent studies in animal models have demonstrated that coronary reperfusion with high-density lipoproteins (HDL) may reduce MI size in up to 30%. A spectrum of mechanisms mediated by either HDL-related apolipoproteins or phospholipids attenuates myocardial cell death. Hence, promising therapeutic approaches such as infusion of reconstituted HDL particles, new HDL by genomic therapy, or the infusion of apoA-I mimetic peptides have been sought as a way of ensuring protection against I/R injury. In this review, we will explore the limitations and potential therapeutic effects of HDL therapies during the acute phase of MI.

Carotid adventitial vasa vasorum and intima-media thickness in a primary prevention population.

BACKGROUND: Vasa vasorum (VV) vessels are critical in the genesis of atherosclerosis. Therefore, we assessed measures of carotid VV, intima-media thickness (CIMT), and patient risk factors in a primary prevention population. METHODS: We used multivariable linear models to evaluate the relationship between baseline covariates and a measure of carotid VV (VV ratio) and CIMT among 324 diabetics and 141 nondiabetics. RESULTS: Median CIMT (in mm) and VV ratio among nondiabetics were 0.82 ± 0.22 and 0.80 ± 0.19, respectively, and 1.06 ± 0.19 and 1.21 ± 0.26 among diabetics (P < 0.0001). Diabetes was associated with 36% (95% CI: 24.3-48.0, P < 0.001) higher VV ratio whereas a unit change in BMI was associated with ≈1% (95% CI: 0.5-1.4, P < 0.001) change in VV ratio. A 10-year increase in age was associated with 4% (95% CI: 1-7, P = 0.005) higher CIMT. Each 10 mmHg increase in mean systolic blood pressure was associated with 2% (95% CI: 1-4, P = 0.003) higher CIMT whereas diabetes conferred 31% (95% CI: 19.1-42.1, P < 0.001) higher CIMT. Female sex was associated with a 9% (95% CI: -12.9 to -4.1, P < 0.001) lower CIMT. Low density lipoprotein (LDL) cholesterol, blood pressure, and CIMT were not significantly associated with VV ratio. CONCLUSION: In this cohort of patients with low CIMT, VV ratio, and CIMT were distinctly unrelated, but each independently associated with diabetes. VV ratio and CIMT relationships warrant further investigation in large-scale studies and across a spectrum of atherosclerostic states.

The role of carotid ultrasound in assessing carotid atherosclerosis in individuals at low-to-intermediate cardiovascular risk.

INTRODUCTION AND OBJECTIVES: Detection of carotid atherosclerosis might help to better identify individuals susceptible to cardiovascular events. We aimed to quantify the number of participants with carotid atherosclerosis and low-to-intermediate cardiovascular risk according to the traditional risk factor scoring, and therefore with an elevated risk of cardiovascular events. METHODS: Cross-sectional, observational study performed during a cardiovascular screening program. From a total of 3778 volunteers, low-to-intermediate cardiovascular risk individuals (N=2354) were identified and studied. Physical examination, blood test, and carotid ultrasound followed standard procedures. Common, bulb, and internal carotid arteries were examined and common carotid intima-media thickness was measured. SCORE risk value was calculated for all participants. Univariate and multivariate statistical analysis was performed. RESULTS: Mean age of participants was 58.9 (15) years, 43.8% were men, 23.7% had hypertension, and 20.5% had hypercholesterolemia. The mean SCORE value was 1.47 (1.4). Both carotid intima-media thickness and the prevalence of carotid plaques increased steadily and significantly (P<.005) as advanced decades of life were analyzed. Variables significantly related with the presence of carotid atherosclerosis were age, male sex, and systolic blood pressure. Interestingly, 592 (25.1%) individuals were reclassified to a higher risk due to the presence of carotid atherosclerosis. CONCLUSIONS: There was a clear dissociation between cardiovascular risk scoring and the presence of atherosclerosis, because 1 of 4 study participants at low-to-intermediate cardiovascular risk had carotid atherosclerosis.

Contrast-enhanced ultrasound imaging of periadventitial vasa vasorum in human carotid arteries.

AIMS: Arterial vasa vasorum (VV) are known to be involved in the atherosclerotic process. The aim of the present study was to explore whether ultrasound imaging with contrast agent is able to visualize adventitial VV in human carotid atherosclerosis. METHODS AND RESULTS: We studied with standard ultrasound 25 patients with carotid stenosis >50% (ATS group) and 15 patients without carotid artery plaques and an intima-media thickness (IMT) <1.0 mm (CTRL group). All patients underwent contrast ultrasound to evaluate periadventitial VV and B-flow imaging (BFI) modality was used to improve and measure periadventitial flow signal. On contrast-enhanced images, a fast microbubble flow and a homogeneous and linear periadventitial contrast signal using BFI were detectable in the adventitial area in all patients of both groups. Periadventitial signal thickness by BFI was higher in patients with atherosclerosis than in the control group (mean +/- SD: CTRL 0.80+/-0.06 mm; ATS 1.10+/-0.11 mm; P<0.001). Moreover, considering the whole study population, the adventitial signal thickness significantly correlated with IMT values (r=0.88, r(2)=0.77; P<0.0001). CONCLUSION: Periadventitial contrast signal was detected in all patients and BFI thickness was higher in patient with carotid atherosclerosis and correlated with IMT.

Individual assessment of arteriosclerosis by empiric clinical profiling.

BACKGROUND: Arteriosclerosis is a common cause of chronic morbidity and mortality. Myocardial infarction, stroke or other cardiovascular events identify vulnerable patients who suffer from symptomatic arteriosclerosis. Biomarkers to identify vulnerable patients before cardiovascular events occur are warranted to improve care for affected individuals. We tested how accurately basic clinical data can describe and assess the activity of arteriosclerosis in the individual patient. METHODOLOGY/PRINCIPAL FINDINGS: 269 in-patients who were treated for various conditions at the department of general medicine of an academic tertiary care center were included in a cross-sectional study. Personal history and clinical examination were obtained. When paraclinical tests were performed, the results were added to the dataset. The numerical variables in the clinical examination were statistically compared between patients with proven symptomatic arteriosclerosis (n = 100) and patients who had never experienced cardiovascular events in the past (n = 110). 25 variables were different between these two patient groups and contributed to the disease activity score. The percentile distribution of these variables defined the empiric clinical profile. Anthropometric data, signs of arterial, cardiac and renal disease, systemic inflammation and health economics formed the major categories of the empiric clinical profile that described an individual patient's disease activity. The area under the curve of the receiver operating curve for symptomatic arteriosclerosis was 0.891 (95% CI 0.799-0.983) for the novel disease activity score compared to 0.684 (95% CI 0.600-0.769) for the 10-year risk calculated according to the Framingham score. In patients suffering from symptomatic arteriosclerosis, the disease activity score deteriorated more rapidly after two years of follow-up (from 1.25 to 1.48, P = 0.005) compared to age- and sex-matched individuals free of cardiovascular events (from 1.09 to 1.19, P = 0.125). CONCLUSIONS/SIGNIFICANCE: Empiric clinical profiling and the disease activity score that are based on accessible, available and affordable clinical data are valid markers for symptomatic arteriosclerosis.