Michael T. Lu

Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial.

BACKGROUND HIV-infected patients have a high risk of myocardial infarction. We aimed to assess the ability of statin treatment to reduce arterial inflammation and achieve regression of coronary atherosclerosis in this population. METHODS In a randomised, double-blind, placebo-controlled trial, 40 HIV-infected participants with subclinical coronary atherosclerosis, evidence of arterial inflammation in the aorta by fluorodeoxyglucose (FDG)-PET, and LDL-cholesterol concentration of less than 3.37 mmol/L (130 mg/dL) were randomly assigned (1:1) to 1 year of treatment with atorvastatin or placebo. Randomisation was by the Massachusetts General Hospital (MGH) Clinical Research Pharmacy with a permuted-block algorithm, stratified by sex with a fixed block size of four. Study codes were available only to the MGH Research Pharmacy and not to study investigators or participants. The prespecified primary endpoint was arterial inflammation as assessed by FDG-PET of the aorta. Additional prespecified endpoints were non-calcified and calcified plaque measures and high risk plaque features assessed with coronary CT angiography and biochemical measures. Analysis was done by intention to treat with all available data and without imputation for missing data. The trial is registered with ClinicalTrials.gov, number NCT00965185. FINDINGS The study was done from Nov 13, 2009, to Jan 13, 2014. 19 patients were assigned to atorvastatin and 21 to placebo. 37 (93%) of 40 participants completed the study, with equivalent discontinuation rates in both groups. Baseline characteristics were similar between groups. After 12 months, change in FDG-PET uptake of the most diseased segment of the aorta was not different between atorvastatin and placebo, but technically adequate results comparing longitudinal changes in identical regions could be assessed in only 21 patients (atorvastatin Δ -0.03, 95% CI -0.17 to 0.12, vs placebo Δ -0.06, -0.25 to 0.13; p=0.77). Change in plaque could be assessed in all 37 people completing the study. Atorvastatin reduced non-calcified coronary plaque volume relative to placebo: median change -19.4% (IQR -39.2 to 9.3) versus 20.4% (-7.1 to 94.4; p=0.009, n=37). The number of high-risk plaques was significantly reduced in the atorvastatin group compared with the placebo group: change in number of low attenuation plaques -0.2 (95% CI -0.6 to 0.2) versus 0.4 (0.0, 0.7; p=0.03; n=37); and change in number of positively remodelled plaques -0.2 (-0.4 to 0.1) versus 0.4 (-0.1 to 0.8; p=0.04; n=37). Direct LDL-cholesterol (-1.00 mmol/L, 95% CI -1.38 to 0.61 vs 0.30 mmol/L, 0.04 to 0.55, p<0.0001) and lipoprotein-associated phospholipase A2 (-52.2 ng/mL, 95% CI -70.4 to -34.0, vs -13.3 ng/mL, -32.8 to 6.2; p=0.005; n=37) decreased significantly with atorvastatin relative to placebo. Statin therapy was well tolerated, with a low incidence of clinical adverse events. INTERPRETATION No significant effects of statin therapy on arterial inflammation of the aorta were seen as measured by FDG-PET. However, statin therapy reduced non-calcified plaque volume and high-risk coronary plaque features in HIV-infected patients. Further studies should assess whether reduction in high-risk coronary artery disease translates into effective prevention of cardiovascular events in this at-risk population. FUNDING National Institutes of Health, Harvard Clinical and Translational Science Center, National Center for Research Resources.

Axial and Reformatted Four-Chamber Right Ventricle–to–Left Ventricle Diameter Ratios on Pulmonary CT Angiography as Predictors of Death After Acute Pulmonary Embolism

OBJECTIVE The purpose of this article is to retrospectively compare right ventricular-to-left ventricular (RV/LV) diameter ratios measured on the standard axial view versus the reformatted four-chamber view as predictors of mortality after acute pulmonary embolism (PE). MATERIALS AND METHODS Six hundred seventy-four consecutive patients (mean age, 58 years; 372 women) with a diagnosis of acute PE on pulmonary CT angiography were considered. The axial and reformatted four-chamber RV/LV diameter ratios were compared as predictors of 30-day all-cause and PE-related mortality. RESULTS Ninety-seven patients (14%) died within 30 days; 39 deaths were PE related. There was no significant difference in the univariate hazard ratios (HRs) of axial and four-chamber RV/LV diameter ratios greater than 0.9 for both all-cause (HR, 2.13 [95% CI, 1.29-3.51] vs HR, 1.95 [95% CI, 1.22-3.14]; p = 0.74) and PE-related (HR, 19.6 [95% CI, 2.70-143] vs HR, 21.8 [95% CI, 2.99-158]; p = 1.0) mortality. Axial and four-chamber multivariate HRs accounting for potential confounders such as age and cancer were also similar for all-cause (HR, 1.79 [95% CI, 1.07-2.99] vs HR, 1.54 [95% CI, 0.95-2.49]; p = 0.62) and PE-related (HR, 16.3 [95% CI, 2.22-119] vs HR, 17.7 [95% CI, 2.43-130]; p = 1.0) mortality. There was no significant difference in sensitivity, specificity, negative predictive value, or positive predictive value. Axial and four-chamber measurements were well correlated (correlation coefficient, 0.857), and there was no significant difference in overall accuracy for predicting all-cause (area under the curve [AUC], 0.582 vs 0.577; p = 0.72) and PE-related (AUC, 0.743 vs 0.744; p = 1.0) mortality. CONCLUSION The axial RV/LV diameter ratio is no less accurate than the reformatted four-chamber RV/LV diameter ratio for predicting 30-day mortality after PE.

Imaging in Acute Pulmonary Embolism With Special Clinical Scenarios

Major advances in computed tomography (CT) technology, specifically multidetector CT (MDCT) with vastly improved spatial and temporal resolution,1 have led to a surge in the diagnosis of acute pulmonary embolism (PE) using computed tomography pulmonary angiography (CTPA).2,–,5 For persons between 35 and 74 years old, hospital diagnosis rates in 1981 for PE were 127.7 per 100 000 for blacks and 98.2 per 100 000 in whites.6 The reported incidence ranges from 43.7 to 145.0 per 100 000.7 These data are based on epidemiological studies based on physical examination and history, which underestimate the actual frequency of disease.8 However, data from autopsies confirms that only a small number of cases of PE are recognized clinically.8 If untreated, the hospital mortality rate for major PE is 30%, whereas the mortality drops markedly in anticoagulated patients,9 emphasizing the need for rapid, accurate imaging for diagnosis and prognosis. Although CTPA has largely solved the diagnostic question, “Does the patient have PE?” new questions have arisen. These include: Do patients warrant concurrent CTPA plus imaging of the pelvis and lower extremities? What is the risk for subsequent PE after negative CTPA? Is there an ideal management algorithm in patients with isolated subsegmental PE? What is the optimal imaging tool for evaluation of women who are either pregnant or of child bearing age? How can the patient radiation doses be reduced without compromising diagnostic capabilities? This review is to address these questions and looks toward the future of PE imaging. Before the mid 1990s, ventilation perfusion scanning (V/Q) was the imaging modality of choice for the evaluation of patients with clinically suspected acute PE. In 1979, V/Q lung scanning was used for 80% of patients.10 By 2001, CT use surpassed V/Q imaging.4 In …

2013 American College of Cardiology/American Heart Association and 2004 Adult Treatment Panel III cholesterol guidelines applied to HIV-infected patients with/without subclinical high-risk coronary plaque

Background:The 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines are being applied to HIV-infected patients but have not been validated in this at-risk population, which is known to have a high prevalence of subclinical high-risk morphology (HRM) coronary atherosclerotic plaque. Objective:To compare recommendations for statins among HIV-infected subjects with/without HRM coronary plaque according to 2013 ACC/AHA versus 2004 Adult Treatment Panel III guidelines. Methods/design:Data from 108 HIV-infected subjects without known cardiovascular disease (CVD) or lipid-lowering treatment who underwent contrast-enhanced computed tomography angiography were analyzed. Recommendations for statin therapy according to 2013 versus 2004 guidelines were assessed among those with/without HRM coronary plaque. Results:Among all subjects, 10-year atherosclerotic cardiovascular disease (ASCVD) risk score was 3.3% (1.6, 6.6), yet 36% of subjects had HRM coronary plaque. Among those with HRM coronary plaque, statins would be recommended for 26% by 2013 guidelines versus 10% by 2004 guidelines (P = 0.04). Conversely, among those without HRM coronary plaque, statins would be recommended for 19% by 2013 guidelines versus 7% by 2004 guidelines (P = 0.005). In multivariate modeling, while 10-year ASCVD risk score related to HRM coronary plaque burden (P = 0.02), so too did other factors not incorporated into 2013 guidelines. Conclusion:The 2013 ACC/AHA cholesterol guidelines recommend statin therapy for a higher percentage of subjects with and without HRM coronary plaque relative to 2004 guidelines. However, even by 2013 guidelines, statin therapy would not be recommended for the majority (74%) of HIV-infected subjects with subclinical HRM coronary plaque. Outcome studies are needed to determine the utility of new statin recommendations and the contribution of HRM coronary plaque to CVD events among HIV-infected subjects.

High-Risk Coronary Plaque at Coronary CT Angiography Is Associated with Nonalcoholic Fatty Liver Disease, Independent of Coronary Plaque and Stenosis Burden: Results from the ROMICAT II Trial

PURPOSE To determine the association between nonalcoholic fatty liver disease (NAFLD) and the presence of high-risk coronary atherosclerotic plaque as assessed with coronary computed tomographic (CT) angiography. MATERIALS AND METHODS This study was approved by the local ethics committees; informed consent was obtained. Patients randomized to the coronary CT angiography arm of the Rule Out Myocardial Infarction using Computer Assisted Tomography, or ROMICAT, II trial who underwent both nonenhanced CT to assess calcium score and contrast material-enhanced coronary CT angiography were included. Readers assessed coronary CT angiography images for the presence of coronary plaque, significant stenosis (≥50%), and high-risk plaque features (positive remodeling, CT attenuation < 30 HU, napkin-ring sign, spotty calcium). NAFLD was defined as hepatic steatosis at nonenhanced CT (liver minus spleen CT attenuation < 1 HU) without evidence of clinical liver disease, liver cirrhosis, or alcohol abuse. To determine the association between high-risk plaque and NAFLD, univariable and multivariable logistic regression analyses were performed, with high-risk plaque as a dependent variable and NAFLD, traditional risk factors, and extent of coronary atherosclerosis as independent variables. RESULTS Overall, 182 (40.9%) of 445 patients had CT evidence of NAFLD. High-risk plaque was more frequent in patients with NAFLD than in patients without NAFLD (59.3% vs 19.0%, respectively; P < .001). The association between NAFLD and high-risk plaque (odds ratio, 2.13; 95% confidence interval: 1.18, 3.85) persisted after adjusting for the extent and severity of coronary atherosclerosis and traditional risk factors. CONCLUSION NAFLD is associated with advanced high-risk coronary plaque, independent of traditional cardiovascular risk factors and the extent and severity of coronary artery disease.

Computed tomography-based high-risk coronary plaque score to predict acute coronary syndrome among patients with acute chest pain--Results from the ROMICAT II trial.

BACKGROUND Coronary computed tomography angiography (CTA) can be used to detect and quantitatively assess high-risk plaque features. OBJECTIVE To validate the ROMICAT score, which was derived using semi-automated quantitative measurements of high-risk plaque features, for the prediction of ACS. MATERIAL AND METHODS We performed quantitative plaque analysis in 260 patients who presented to the emergency department with suspected ACS in the ROMICAT II trial. The readers used a semi-automated software (QAngio, Medis medical imaging systems BV) to measure high-risk plaque features (volume of <60HU plaque, remodeling index, spotty calcium, plaque length) and diameter stenosis in all plaques. We calculated a ROMICAT score, which was derived from the ROMICAT I study and applied to the ROMICAT II trial. The primary outcome of the study was diagnosis of an ACS during the index hospitalization. RESULTS Patient characteristics (age 57 ± 8 vs. 56 ± 8 years, cardiovascular risk factors) were not different between those with and without ACS (prevalence of ACS 7.8%). There were more men in the ACS group (84% vs. 59%, p = 0.005). When applying the ROMICAT score derived from the ROMICAT I trial to the patient population of the ROMICAT II trial, the ROMICAT score (OR 2.9, 95% CI 1.4-6.0, p = 0.003) was a predictor of ACS after adjusting for gender and ≥ 50% stenosis. The AUC of the model containing ROMICAT score, gender, and ≥ 50% stenosis was 0.91 (95% CI 0.86-0.96) and was better than with a model that included only gender and ≥ 50% stenosis (AUC 0.85, 95%CI 0.77-0.92; p = 0.002). CONCLUSIONS The ROMICAT score derived from semi-automated quantitative measurements of high-risk plaque features was an independent predictor of ACS during the index hospitalization and was incremental to gender and presence of ≥ 50% stenosis.

Reducing the Rate of Repeat Imaging: Import of Outside Images to PACS

OBJECTIVE Repeat imaging at the transfer of care between institutions is a potential source of overutilization. The purpose of this study was to assess whether importing images obtained at one institution to the PACS at another institution reduces the number of repeat imaging examinations performed, sparing patients unnecessary cost and radiation. MATERIALS AND METHODS Informed consent was waived for this retrospective study, which included 267 patients who had undergone CT or MRI of the abdomen at our or another institution within 4 months before transarterial chemoembolization. Patients were divided into the following four groups based on the availability of their images from institutions other than ours (outside images): outside imaging performed but images not available; outside images available on CD or film but not imported; outside images imported to PACS; and no outside imaging, that is, all imaging performed at our institution. The rates of repeat imaging in the four groups were compared. RESULTS When outside images were not available, 72% (13/18) of patients underwent repeat imaging; when outside images were available but not imported, 52% (14/27); when outside images were imported to PACS, 11% (9/79); and when imaging was performed only at our institution, 13% (18/143). Patients whose outside images were imported were significantly less likely to undergo repeat imaging than were both groups whose outside images were not imported (p < 0.001), and their rate of repeat imaging was similar to that of patients who did not undergo outside imaging (p = 0.79). After adjustment for potential confounders, including age, sex, referring institution, and size and number of lesions, the odds that a patient whose images were imported would undergo repeat imaging were significantly lower than those of a patient whose outside images were not imported (odds ratios, 31 for images not available and 9.0 for images available but not imported; both p < 0.001) and were similar to those of a patient who underwent all imaging at our institution (odds ratio, 0.71; p = 0.51). CONCLUSION Importing outside images to PACS reduces the rate of repeat imaging.

The variability in prognostic values of right ventricular-to-left ventricular diameter ratios derived from different measurement methods on computed tomography pulmonary angiography: a patient outcome study.

Purpose: To evaluate variability in right ventricular-to-left ventricular (RV/LV) diameter ratios introduced by differences in measurement methods and the subsequent influence on the accuracy of predicting outcomes for patients with acute pulmonary embolism (PE). Materials and Methods: For 200 consecutive computed tomography pulmonary angiograms positive for acute PE, RV/LV diameter ratios were retrospectively measured using 3 different 4-chamber reformations and from axial images alone. The first 4-chamber reformation method (4ch-1) was a single oblique technique using LV morphology landmarks; the other 2 methods (4ch-2 and 4ch-3) were double oblique techniques that created an intermediate short-axis image to identify the maximum RV diameter but with different approaches to reach short-axis images. Interobserver variability was measured using 30 cases. Receiver-operating characteristic analysis compared the accuracy of predicting outcomes among the 4 measurements for PE-related death, and for death or the need for intensive therapies (composite outcome). Results: The difference in median RV/LV diameter ratios was insignificant among 4ch-2 (1.01), 4ch-3 (1.02), and axial (1.03) datasets, whereas that from 4ch-1 (0.93) was significantly lower (P<0.001). Correlation between observers was excellent for all 4 datasets (r=0.881 to 0.925). Compared with 4ch-1, the other 3 datasets equally achieved higher accuracy in predicting PE-related 30-day mortality (area under curve: 0.55 vs. 0.69 to 0.73, P=0.007 to 0.019) and a composite outcome (area under curve: 0.65 vs. 0.77 to 0.78, P=0.003 to 0.010). Conclusions: Double oblique 4-chamber reformation methods that use intermediate short-axis images to optimize RV size predict outcomes better in patients with acute PE than do single oblique methods using only LV landmarks; however, their accuracy is not superior to that from measurements based on axial images.

Cardiovascular Toxicity of Illicit Anabolic-Androgenic Steroid Use

Background: Millions of individuals have used illicit anabolic-androgenic steroids (AAS), but the long-term cardiovascular associations of these drugs remain incompletely understood. Methods: Using a cross-sectional cohort design, we recruited 140 experienced male weightlifters 34 to 54 years of age, comprising 86 men reporting ≥2 years of cumulative lifetime AAS use and 54 nonusing men. Using transthoracic echocardiography and coronary computed tomography angiography, we assessed 3 primary outcome measures: left ventricular (LV) systolic function (left ventricular ejection fraction), LV diastolic function (early relaxation velocity), and coronary atherosclerosis (coronary artery plaque volume). Results: Compared with nonusers, AAS users demonstrated relatively reduced LV systolic function (mean±SD left ventricular ejection fraction = 52±11% versus 63±8%; P<0.001) and diastolic function (early relaxation velocity = 9.3±2.4 cm/second versus 11.1±2.0 cm/second; P<0.001). Users currently taking AAS at the time of evaluation (N=58) showed significantly reduced LV systolic (left ventricular ejection fraction = 49±10% versus 58±10%; P<0.001) and diastolic function (early relaxation velocity = 8.9±2.4 cm/second versus 10.1±2.4 cm/second; P=0.035) compared with users currently off-drug (N=28). In addition, AAS users demonstrated higher coronary artery plaque volume than nonusers (median [interquartile range] 3 [0, 174] mL3 versus 0 [0, 69] mL3; P=0.012). Lifetime AAS dose was strongly associated with coronary atherosclerotic burden (increase [95% confidence interval] in rank of plaque volume for each 10-year increase in cumulative duration of AAS use: 0.60 SD units [0.16–1.03 SD units]; P=0.008). Conclusions: Long-term AAS use appears to be associated with myocardial dysfunction and accelerated coronary atherosclerosis. These forms of AAS-associated adverse cardiovascular phenotypes may represent a previously underrecognized public-health problem.

Effects of Antiretroviral Therapy on Immune Function and Arterial Inflammation in Treatment-Naive Patients With Human Immunodeficiency Virus Infection

IMPORTANCE Individuals with human immunodeficiency virus (HIV) infection receiving combined antiretroviral therapy (ART) have an increased risk of myocardial infarction. Effects of ART on arterial inflammation among treatment-naive individuals with HIV are unknown. OBJECTIVE To determine the effects of newly initiated ART on arterial inflammation and other immune/inflammatory indices in ART-naive patients with HIV infection. DESIGN, SETTING, PARTICIPANTS Twelve treatment-naive HIV-infected individuals underwent fludeoxyglucose F 18 ([18F]-FDG) positron emission tomographic scanning for assessment of arterial inflammation, coronary computed tomographic angiography for assessment of subclinical atherosclerosis, and systemic immune and metabolic phenotyping before and 6 months after the initiation of therapy with elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (combined ART). Systemic immune and metabolic factors were also assessed in 12 prospectively recruited individuals without HIV serving as controls. The study began July 24, 2012, and was completed May 7, 2015. INTERVENTIONS Combined ART in the HIV-infected cohort. MAIN OUTCOMES AND MEASURES The primary outcome was change in aortic target-background ratio (TBR) on [18F]-FDG-PET with combined ART in the HIV-infected group. RESULTS For the 12 participants with HIV infection (mean (SD) age, 35 [11] years), combined ART suppressed viral load (mean [SD] log viral load, from 4.3 [0.6] to 1.3 [0] copies/mL; P < .001), increased the CD4+ T-cell count (median [IQR], from 461 [332-663] to 687 [533-882] cells/mm3; P < .001), and markedly reduced percentages of circulating activated CD4+ T cells (human leukocyte antigen-D related [HLA-DR]+CD38+CD4+) (from 3.7 [1.8-5.0] to 1.3 [0.3-2.0]; P = .008) and CD8+ T cells (HLA-DR+CD38+CD8+) (from 18.3 [8.1-27.0] to 4.0 [1.5-7.8]; P = .008), increased the percentage of circulating classical CD14+CD16- monocytes (from 85.8 [83.7-90.8] to 91.8 [87.5-93.2]; P = .04), and reduced levels of CXCL10 (mean [SD] log CXCL10, from 2.4 [0.4] to 2.2 [0.4] pg/mL; P = .03). With combined ART, uptake of [18F]-FDG in the axillary lymph nodes, as measured by TBR, decreased from a median (IQR) of 3.7 (1.3-7.0) at baseline to 1.4 (0.9-1.9; P = .01) at study end. In contrast, no significant decrease was seen in aortic TBR in response to combined ART (mean [SD], 1.9 [0.2]; median [IQR], 2.0 [1.8-2.1] at baseline to 2.2 [0.4]; 2.1 [1.9-2.6], respectively, at study end; P = .04 by 2-way test, P = .98 for test of decrease by 1-way test). Changes in aortic TBR during combined ART were significantly associated with changes in lipoprotein-associated phospholipase A2 (n = 10; r = 0.67; P = .03). Coronary plaque increased among 3 participants with HIV infection with baseline plaque and developed de novo in 1 participant during combined ART. CONCLUSIONS AND RELEVANCE Newly initiated combined ART in treatment-naive individuals with HIV infection had discordant effects to restore immune function without reducing arterial inflammation. Complementary strategies to reduce arterial inflammation among ART-treated HIV-infected individuals may be needed.