Subclinical Atherosclerosis Imaging in People Living with HIV

Abstract

In many, but not all studies, people living with HIV (PLWH) have an increased risk of coronary artery disease (CAD) events compared to the general population. This has generated considerable interest in the early, non-invasive detection of asymptomatic (subclinical) atherosclerosis in PLWH. Ultrasound studies assessing carotid artery intima-media thickness (CIMT) have tended to show a somewhat greater thickness in HIV+ compared to HIV-, likely due to an increased prevalence of cardiovascular (CV) risk factors in PLWH. Coronary artery calcification (CAC) determination by non-contrast computed tomography (CT) seems promising to predict CV events but is limited to the detection of calcified plaque. Coronary CT angiography (CCTA) detects calcified and non-calcified plaque and predicts CAD better than either CAC or CIMT. A normal CCTA predicts survival free of CV events over a very long time-span. Research imaging techniques, including black-blood magnetic resonance imaging of the vessel wall and 18F-fluorodeoxyglucose positron emission tomography for the assessment of arterial inflammation have provided insights into the prevalence of HIV-vasculopathy and associated risk factors, but their clinical applicability remains limited. Therefore, CCTA currently appears as the most promising cardiac imaging modality in PLWH for the evaluation of suspected CAD, particularly in patients <50 years, in whom most atherosclerotic coronary lesions are non-calcified.

Keywords: HIV infection; accelerated atherosclerosis; carotid intima-media thickness; coronary CT angiography; coronary calcium scoring; fluorodeoxyglucose positron emission tomography; magnetic resonance angiography; subclinical coronary artery disease.

Figure 1

Coronary artery calcium scoring in an asymptomatic 43-year old HIV-positive male patient. Maximum intensity projection depicts extensive calcifications in the left anterior descending artery (purple), in the left circumflex artery (blue), and in the right coronary artery (yellow). The total Agatston score was 1031, classifying this patient as at high risk for future CV events and prompting lifestyle interventions and the initiation of a statin.

Figure 2

Coronary computed tomography angiography of a 48-year old HIV+ female patient with typical angina. The patient had a positive family history for cardiovascular events and was an active smoker, putting her at intermediate risk for having coronary artery disease. Volume rendering (A) of the image datasets depicts normal coronary anatomy, while the curved multiplanar reformats of the left anterior descending (B), the left circumflex (C), and the right coronary (D) arteries reveal only minimal and non-obstructive coronary atherosclerosis in the proximal left anterior descending (white arrow). Coronary artery disease was, therefore, excluded as a cause for her symptoms. BMI 24.2 kg/m². Radiation dose exposure 0.57 mSv. Contrast volume 40 mL.

Figure 3

Non-invasive evaluation of an asymptomatic 65-year old HIV+ male patient. The patient had a history of treated arterial hypertension, was an active smoker and suffered from peripheral artery disease with the latter prompting further cardiovascular work-up despite a normal stress-electrocardiogram. Multiplanar curved reconstruction of the coronary computed tomography angiography dataset (A) reveals multiple calcified but non-obstructive lesions and 70–90% stenosis (white filled arrow) in the mid-right coronary artery. This obstructive lesion (B, cross sectional view) exhibits several morphological high-risk features typical for an event-prone lesion, such as positive remodeling and a low-attenuation core (*) with calcifications only at the edge of the lesion (white empty arrow), constituting the so-called napkin-ring sign.

Figure 4

Evaluation of a 49-year old HIV+ male patient with typical angina. The patient had no cardiovascular risk factors and he was referred for exclusion of coronary artery disease with a calculated pre-test probability of 69%. Total cholesterol was 3.6 mmol/L (<5.0), HDL-cholesterol 1.45 mmol/L (>1.0), and LDL-cholesterol 1.8 mmol/L (<3.0). Maximum intensity projection and multiplanar curved reconstruction of the coronary computed tomography angiography (CCTA) datasets (A) depict a 70–90% stenosis (white filled arrow) in the proximal left anterior descending artery as shown in the cross-section (inlet). As per clinical routine and in accordance with current guidelines, lesions are primarily graded visually with regard to maximal percent diameter stenosis in our institution. In this particular patient, the qualitative evaluation was complemented by quantitative measurements (using version 2 of CardIQ Xpress/GE Healthcare), because the lesion in the LAD was non-calcified, allowing for more accurate lumen delineation due to the lack of blooming artifacts. The quantitative analysis resulted in a diameter stenosis of 75%. Myocardial perfusion single-photon-computed-emission-tomography (SPECT, (B)) confirmed hemodynamical relevance of the lesion, revealing a large perfusion defect during stress (top rows) with reversibility during rest (bottom rows), constituting ischemia in the anteroseptal wall of the left ventricular myocardium. Hybrid CCTA/SPECT imaging (C) clearly demonstrates a large area of ischemia in the myocardium subtended by the left anterior descending artery. Finally, obstructive coronary artery disease (white empty arrow) was confirmed during invasive coronary angiography (D), and the lesion was treated with a drug-eluting stent.

Figure 5

Black-blood MR imaging of the carotid arteries. Fat saturated T2-weighted black-blood MR images at the level of the common carotid arteries in a 56-year-old HIV+ man (A) and a 47-year-old HIV− man (B). Similar imaging technique at the level of the internal carotid arteries (ICAs) in a 56-year-old HIV+ woman (C) shows narrowing of the vascular lumen bilaterally by a plaque (small arrows), more significant on the right side. (D) shows similar imaging at the level of ICAs in a 47-year-old HIV negative man with no evidence of atherosclerosis.

Figure 6

FDG-PET imaging of the major vessels. (A) Coronal FDG PET images, (B) coronal CT scan images and (C) fused PET CT scans show subtle FDG uptake in the vascular wall of the ascending aorta (arrows).