Carol Mitchell

Endothelial Function in Human Immunodeficiency Virus-Infected Antiretroviral-Naive Subjects Before and After Starting Potent Antiretroviral Therapy: The ACTG (AIDS Clinical Trials Group) Study 5152s

OBJECTIVES This study evaluated the effects of 3 class-sparing antiretroviral therapy (ART) regimens on endothelial function in human immunodeficiency virus (HIV)-infected subjects participating in a randomized trial. BACKGROUND Endothelial dysfunction has been observed in patients receiving ART for HIV infection. METHODS This was a prospective, multicenter study of treatment-naive subjects who were randomly assigned to receive a protease inhibitor-sparing regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + efavirenz, a non-nucleoside reverse transcriptase inhibitor-sparing regimen of NRTIs + lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. The NRTIs were lamivudine + stavudine, zidovudine, or tenofovir. Brachial artery flow-mediated dilation (FMD) was determined by B-mode ultrasound before starting on ART, then after 4 and 24 weeks. RESULTS There were 82 subjects (median age 35 years, 91% men, 54% white). Baseline CD4 cell counts and plasma HIV ribonucleic acid (RNA) values were 245 cells/mm(3) and 4.8 log(10) copies/ml, respectively. At baseline, FMD was 3.68% (interquartile range [IQR] 1.98% to 5.51%). After 4 and 24 weeks of ART, plasma HIV RNA decreased by 2.1 and 3.0 log(10) copies/ml, respectively. FMD increased by 0.74% (IQR -0.62% to +2.74%, p = 0.003) and 1.48% (IQR -0.20% to +4.30%, p < 0.001), respectively, with similar changes in each arm (Kruskal-Wallis p value >0.600). The decrease in plasma HIV RNA at 24 weeks was associated with greater FMD (r(s) = -0.30, p = 0.017). CONCLUSIONS Among treatment-naive individuals with HIV, 3 different ART regimens rapidly improved endothelial function. Benefits were similar for all ART regimens, appeared quickly, and persisted at 24 weeks.

Endothelial Function in Human Immunodeficiency Virus-Infected Antiretroviral-Naive Subjects Before and After Starting Potent Antiretroviral Therapy

OBJECTIVES This study evaluated the effects of 3 class-sparing antiretroviral therapy (ART) regimens on endothelial function in human immunodeficiency virus (HIV)-infected subjects participating in a randomized trial. BACKGROUND Endothelial dysfunction has been observed in patients receiving ART for HIV infection. METHODS This was a prospective, multicenter study of treatment-naive subjects who were randomly assigned to receive a protease inhibitor-sparing regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + efavirenz, a non-nucleoside reverse transcriptase inhibitor-sparing regimen of NRTIs + lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. The NRTIs were lamivudine + stavudine, zidovudine, or tenofovir. Brachial artery flow-mediated dilation (FMD) was determined by B-mode ultrasound before starting on ART, then after 4 and 24 weeks. RESULTS There were 82 subjects (median age 35 years, 91% men, 54% white). Baseline CD4 cell counts and plasma HIV ribonucleic acid (RNA) values were 245 cells/mm(3) and 4.8 log(10) copies/ml, respectively. At baseline, FMD was 3.68% (interquartile range [IQR] 1.98% to 5.51%). After 4 and 24 weeks of ART, plasma HIV RNA decreased by 2.1 and 3.0 log(10) copies/ml, respectively. FMD increased by 0.74% (IQR -0.62% to +2.74%, p = 0.003) and 1.48% (IQR -0.20% to +4.30%, p < 0.001), respectively, with similar changes in each arm (Kruskal-Wallis p value >0.600). The decrease in plasma HIV RNA at 24 weeks was associated with greater FMD (r(s) = -0.30, p = 0.017). CONCLUSIONS Among treatment-naive individuals with HIV, 3 different ART regimens rapidly improved endothelial function. Benefits were similar for all ART regimens, appeared quickly, and persisted at 24 weeks.

Preliminary in vivo atherosclerotic carotid plaque characterization using the accumulated axial strain and relative lateral shift strain indices

In this paper, we explore two parameters or strain indices related to plaque deformation during the cardiac cycle, namely, the maximum accumulated axial strain in plaque and the relative lateral shifts between plaque and vessel wall under in vivo clinical ultrasound imaging conditions for possible identification of vulnerable plaque. These strain indices enable differentiation between calcified and lipidic plaque tissue utilizing a new perspective based on the stiffness and mobility of the plaque. In addition, they also provide the ability to distinguish between softer plaques that undergo large deformations during the cardiac cycle when compared to stiffer plaque tissue. Soft plaques that undergo large deformations over the cardiac cycle are more prone to rupture and to release micro-emboli into the cerebral bloodstream. The ability to identify vulnerable plaque, prone to rupture, would significantly enhance the clinical utility of this method for screening patients. We present preliminary in vivo results obtained from ultrasound radio frequency data collected over 16 atherosclerotic plaque patients before these patients undergo a carotid endarterectomy procedure. Our preliminary in vivo results indicate that the maximum accumulated axial strain over a cardiac cycle and the maximum relative lateral shift or displacement of the plaque are useful strain indices that provide differentiation between soft and calcified plaques.

Methods for robust in vivo strain estimation in the carotid artery.

A hierarchical block-matching motion tracking algorithm for strain imaging is presented. Displacements are estimated with improved robustness and precision by utilizing a Bayesian regularization algorithm and an unbiased subsample interpolation technique. A modified least-squares strain estimator is proposed to estimate strain images from a noisy displacement input while addressing the motion discontinuity at the wall-lumen boundary. Methods to track deformation over the cardiac cycle incorporate a dynamic frame skip criterion to process data frames with sufficient deformation to produce high signal-to-noise displacement and strain images. Algorithms to accumulate displacement and/or strain on particles in a region of interest over the cardiac cycle are described. New methods to visualize and characterize the deformation measured with the full 2D strain tensor are presented. Initial results from patients imaged prior to carotid endarterectomy suggest that strain imaging detects conditions that are traditionally considered high risk including soft plaque composition, unstable morphology, abnormal hemodynamics and shear of plaque against tethering tissue can be exacerbated by neoangiogenesis. For example, a maximum absolute principal strain exceeding 0.2 is observed near calcified regions adjacent to turbulent flow, protrusion of the plaque into the arterial lumen and regions of low echogenicity associated with soft plaques. Non-invasive carotid strain imaging is therefore a potentially useful tool for detecting unstable carotid plaque.

Change to atazanavir/ritonavir treatment improves lipids but not endothelial function in patients on stable antiretroviral therapy.

Objective:Protease inhibitors and other antiretroviral drugs have been associated with dyslipidemia, endothelial dysfunction, and increased cardiovascular disease risk. The protease inhibitor atazanavir has an advantageous lipid profile; we studied its effects on arterial function and other metabolic and inflammatory cardiovascular disease risk factors. Design:Prospective, randomized, multinational trial in HIV-infected patients receiving stable protease inhibitor-based therapy with plasma HIV RNA less than 500 copies/ml and fasting low-density lipoprotein cholesterol more than 130 mg/dl, or triglycerides more than 200 mg/dl. Methods:Patients were randomized to continue their current protease inhibitor or switch the protease inhibitor to atazanavir and continue ritonavir if given as a protease inhibitor booster for 24 weeks. Brachial artery flow-mediated dilation, lipoproteins, and inflammatory and metabolic markers were measured at baseline, week 12, and week 24. Median changes within (signed rank test) and between (Wilcoxon test) arms were calculated. Results:Twenty-six patients switched to atazanavir (all continued on ritonavir); 24 remained on their protease inhibitor regimen. Median CD4 cell count was 499 cells/μl, total cholesterol 204 mg/dl, low-density lipoprotein cholesterol 122 mg/dl, and triglycerides 244 mg/dl. There were no significant changes in flow-mediated dilation after 12 and 24 weeks. At 24 weeks, significant changes in the atazanavir vs. continued protease inhibitor group were observed for total cholesterol (−25 vs. +1.5 mg/dl, P = 0.009), triglycerides (−58 vs. +3.5 mg/dl, P = 0.013), and nonhigh-density lipoprotein cholesterol (−27 vs. −0.5 mg/dl, P = 0.014). Conclusion:In dyslipidemic individuals with suppressed HIV RNA on stable therapy, changing the protease inhibitor to atazanavir/ritonavir for 24 weeks improved lipids; however, endothelial function, inflammatory, and metabolic markers did not change.

Radial artery pseudoaneurysm: A maneuver to decrease the risk of thrombin therapy

A pseudoaneurysm is an infrequent complication of arterial intervention. It is most frequently seen in the groin after coronary catheterization but can be seen in any vessel as a sequela of trauma. Pseudoaneurysms can also occur peripherally as the sequela of arteriovenous shunting for dialysis or placement of indwelling catheters or after traumatic drawing of arterial blood gas. Treatment of pseudoaneurysms has evolved through the years. Initially it was the domain of surgical intervention. Subsequently, most cases have been treated with ultrasound-guided compression. Recently thrombin (Jones Pharmacy Inc, St Louis, MO) injection has become the preferred treatment method. However, direct injection of thrombin into a pseudoaneurysm is not without risk. If thrombin should escape the pseudoaneurysm, a clot can propagate into the affected artery and result in embolization or thrombosis of peripheral branch vessels. The severity of the iatrogenic insult is amplified when the blood supply is to more critical areas, such as the head or hand. In this report, a new technique to help minimize the chance of unwanted propagation of the thrombus into the peripheral vasculature during thrombin treatment of a radial artery pseudoaneurysm is described.

Short-term effects of extended-release niacin on endothelial function in HIV-infected patients on stable antiretroviral therapy.

Objective:To assess the short-term effects of extended-release niacin (ERN) on endothelial function in HIV-infected patients with low high-density lipoprotein-cholesterol (HDL-c) levels. Methods:Randomized controlled study to determine the short-term effects of ERN on endothelial function, measured by flow-mediated vasodilation (FMD) of the brachial artery, in HIV-infected adults with low HDL-c. Participants on stable HAART with fasting HDL-c less than 40 mg/dl and low-density lipoprotein-cholesterol less than 130 mg/dl were randomized to ERN or control arms. ERN treatment started at 500 mg/night and titrated to 1500 mg/night for 12 weeks. Controls received the same follow-up but were not given ERN (no placebo). Participants were excluded if they had a history of cardiac disease, uncontrolled hypertension, diabetes mellitus, or were on lipid-lowering medications such as statins and fibrates. Change in FMD was compared between arms with respect to baseline HDL-c. Results:Nineteen participants were enrolled: 89% men, median age 50 years, 53% white/non-Hispanic, median CD4 cell count 493 cells/μl, and 95% of them had HIV RNA below 50 copies/ml. Participants receiving ERN had a median HDL-c (interquartile range) increase of 3.0 mg/dl (0.75 to 5.0) compared with −1.0 mg/dl in controls (−6.0 to 2.5), a P value is equal to 0.04. The median change in FMD was 0.91% (−2.95 to 2.21) for ERN and −0.48% (−2.65 to 0.98) for controls (P = 0.67). However, end of study FMD for ERN was significantly different from controls after adjusting for baseline differences in FMD and HDL-c, 6.36% (95% confidence interval 4.85–7.87) and 2.73% (95% confidence interval 0.95–4.51) respectively, a P value is equal to 0.048. Conclusion:This pilot study demonstrated that short-term niacin therapy could improve endothelial function in HIV-infected patients with low HDL-c.

Radiation Safety for the Cardiac Sonographer: Recommendations of the Radiation Safety Writing Group for the Council on Cardiovascular Sonography of the American Society of Echocardiography

Elizabeth F. McIlwain, MHS, RCS, FASE (Chair), Patrick D. Coon, RCCS, RDCS, FASE, Andrew J. Einstein, MD, PhD, Carol K. C. Mitchell, PhD, RDMS, RDCS, RVT, RT(R), FASE, Gregory W. Natello, DO, FASE, Richard A. Palma, BS, RDCS, RCS, FASE, MargaretM. Park, BS, RDCS, RVT, FASE, Frank Ranallo, PhD, andMarsha L. Roberts, RCS, FASE,NewOrleans, Louisiana; Philadelphia, Pennsylvania; New York, New York; Milwaukee and Madison, Wisconsin; Morristown, New Jersey; Hartford, Connecticut; Cleveland, Ohio; Grand Prairie, Texas

Intraoperative Sonography of Intracranial Arteriovenous Malformations How We Do It

Objective. We have advanced the application of intraoperative neurosonography by combining gray scale sonographic imaging with pulsed wave Doppler and color flow Doppler imaging to guide and confirm resection of arteriovenous malformations of the brain. We want to share our technique with the imaging community. Methods. We present a review of our scan technique as it has evolved over the 3 years during which we have been assisting our neurosurgical team. Results and Conclusions. Our experience has indicated that a combination of sonographic imaging and color and spectral Doppler imaging improves surgical resection of such lesions.

The relationship between carotid artery plaque stability and white matter ischemic injury

Higher local carotid artery strain has previously been shown to be a characteristic of unstable carotid plaques. These plaques may be characterized by microvascular changes that predispose to intraplaque hemorrhage, increasing the likelihood of embolization. Little is known however, about how these strain indices correspond with imaging markers of brain health and metrics of brain structure. White matter hyperintensities (WMHs), which are bright regions seen on T2-weighted brain MRI imaging, are postulated to result from cumulative ischemic vascular injury. Consequently, we hypothesized that plaques that are more prone to microvascular changes and embolization, represented by higher strain indices on ultrasound, would be associated with an increased amount of WMH lesion volume. This relationship would suggest not only emboli as a cause for the brain degenerative changes, but more importantly, a common microvascular etiology for large and small vessel contributions to this process. Subjects scheduled to undergo a carotid endarterectomy were recruited from a neurosurgery clinic. Prior to surgery, participating subjects underwent both ultrasound strain imaging and brain MRI scans as part of a larger clinical study on vascular health and cognition. A linear regression found that maximum absolute strain and peak to peak strain in the surgical side carotid artery were predictive of WMH burden. Furthermore, the occurrence of microembolic signals monitored using transcranial Doppler (TCD) ultrasound examinations also correlated with increasing lesion burden. It is becoming increasingly recognized that cognitive decline is often multifactorial in nature. One contributing extra-brain factor may be changes in the microvasculature that produce unstable carotid artery plaques. In this study, we have shown that higher strain indices in carotid artery plaques are significantly associated with an increased WMH burden, a marker of vascular mediated brain damage.