Stefano Coli

Contrast-Enhanced Ultrasound Imaging of Intraplaque Neovascularization in Carotid Arteries: Correlation With Histology and Plaque Echogenicity

OBJECTIVES This study was designed to evaluate contrast-enhanced ultrasound imaging of carotid atherosclerosis as a clinical tool to study intraplaque neovascularization. BACKGROUND Plaque neovascularization is associated with plaque vulnerability and symptomatic disease; therefore, imaging of neovascularization in carotid atherosclerosis may represent a useful tool for clinical risk stratification and monitoring the efficacy of antiatherosclerotic therapies. METHODS Thirty-two patients with 52 carotid plaques were studied by standard and contrast-enhanced ultrasound imaging. In 17 of these patients who underwent endarterectomy, the surgical specimen was available for histological determination of microvessel density by CD31/CD34 double staining. Plaque echogenicity and degree of stenosis at standard ultrasound imaging were evaluated for each lesion. Contrast-agent enhancement within the plaque was categorized as absent/peripheral (grade 1) and extensive/internal (grade 2). RESULTS In the surgical subgroup, plaques with higher contrast-agent enhancement showed a greater neovascularization at histology (grade 2 vs. grade 1 contrast-agent enhancement: median vasa vasorum density: 3.24/mm(2) vs. 1.82/mm(2), respectively, p = 0.005). In the whole series of 52 lesions, echolucent plaques showed a higher degree of contrast-agent enhancement (p < 0.001). Stenosis degree was not associated with neovascularization at histology or with the grade of contrast-agent enhancement. CONCLUSIONS Carotid plaque contrast-agent enhancement with sonographic agents correlates with histological density of neovessels and is associated with plaque echolucency, a well-accepted marker of high risk lesions, but it is unrelated to the degree of stenosis. Contrast-enhanced carotid ultrasound imaging may provide valuable information for plaque risk stratification and for assessing the response to antiatherosclerotic therapies, beyond that provided by standard ultrasound imaging.

Two Different Mechanisms of Myocardial Ischemia Involving 2 Separate Myocardial Segments in a Patient With Normal Coronary Angiography

A 53-year-old woman with no risk factors was admitted to our hospital in December 2006 because of worsening angina and positive exercise stress test. Two months earlier, she had been admitted to another hospital because of prolonged epigastrial pain without radiation, which had subsided just before she reached the hospital, that was associated with diagnostic elevation of troponin; she reported 3 episodes of the same pain lasting ≈5 minutes in the early morning hours over the preceding 3 weeks. A few hours after admission, she had a recurrence of pain with ST elevation on the inferior electrocardiogram (ECG) leads that responded to intravenous nitrates. Subsequent angiography failed to show lumen stenosis, irregularities, and thrombus deposition, but ventriculography showed akinesia of the basal inferior wall. The discharge diagnosis was inferior ST-elevation myocardial infarction (creatine kinase-MB peak, 112 U/L; troponin I peak, 9.74 ng/mL) with normal coronary arteries, and she was prescribed aspirin, calcium, antagonists, and β-blockers. She remained symptom free for about a month. Then, during a very stressful period of her life, she began to present with anginal pain during effort, sometimes on emotion. She insisted …

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.

Assessment of Takayasu Arteritis Activity by Carotid Contrast-Enhanced Ultrasound

A 35-year-old woman was admitted to our institute with a 5-year history of fatigue and low-grade fever. Six months before admission, she had pain in the neck and in the infrascapular region. On admission, the patients heart rate was 80 bpm, her temperature was 37.3°C, and her blood pressure was 130/70 mm Hg in the right arm and 110/70 mm Hg in the left arm. Examination of the neck revealed no jugular venous distention but disclosed bilateral carotid murmurs. Cardiac examination revealed a regular rate and rhythm with a 3/6 holosystolic murmur audibled at the left sternal border. Lung fields were normal. Abdominal examination findings were normal, except for the presence of a palpable spleen and an abdominal bruit at the umbilical left lumbar region. Laboratory examination revealed hemoglobin, 8.5 g/dL (reference ranges, 12.0 to 15.5 g/dL); leukocytes, 21.7×109/L (3.5 to 10.5×109/L); platelets, 460×109/L (150 to 450×109/L); mean corpuscular volume, 76.0 fL (81.6 to 98.3 fL); erythrocyte sedimentation rate, 120 mm/h (0 to 20 mm/h); and …

Mild inflammatory activation of mammary arteries in patients with acute coronary syndromes

Acute coronary syndromes (ACS) are characterized by multiple unstable coronary plaques and elevated circulating levels of inflammatory biomarkers. The endothelium of internal mammary arteries (IMA), which are atherosclerosis resistant, is exposed to proinflammatory stimuli as vessels that develop atherosclerosis. Our study investigated the IMA endothelial expression of inflammatory molecules in patients with ACS or chronic stable angina (CSA). IMA demonstrated normal morphology, intact endothelial lining, and strong immunoreactivity for glucose transporter 1. E-selectin expression was observed more frequently in IMA of ACS patiention than CSA patients (ACS 61% vs. CSA 14%, P = 0.01). High fluorescence for major histocompatibility complex (MHC) was significantly more frequent on the luminal endothelium (ACS 66.7% vs. CSA 17.6%, P = 0.001 for class I; and ACS 66.7% vs. CSA 6.2%, P = 0.0003 for class II-DR) and on the vasa vasorum (ACS 92.9% vs. CSA 33.3% and 7.7%, P = 0.0007 and P < 0.0001 for class I and class II-DR, respectively) of ACS patients than CSA patients. ICAM-1, VCAM-1, Toll-like receptor 4, tissue factor, IL-6, inducible nitric oxide synthase, and TNF-alpha expression were not significantly different in ACS and CSA. Circulating C-reactive protein [ACS 4.8 (2.6-7.3) mg/l vs. CSA 1.8 (0.6-3.5) mg/l, P = 0.01] and IL-6 [ACS 4.0 (2.6-5.5) pg/ml vs. CSA 1.7 (1.4-4.0) pg/ml, P = 0.02] were higher in ACS than CSA, without a correlation with IMA inflammation. The higher E-selectin, MHC class I and MHC class II-DR on the endothelium and vasa vasorum of IMA from ACS patients suggests a mild, endothelial inflammatory activation in ACS, which can be unrelated to the presence of atherosclerotic coronary lesions. These findings indicated IMA as active vessels in coronary syndromes.

Molecular study of human herpesvirus 6 and 8 involvement in coronary atherosclerosis and coronary instability

Several lines of evidence suggest the involvement of infectious agents in the pathogenesis of atherosclerosis. Furthermore, a correlation between infection‐driven inflammatory burden and acute manifestation of coronary artery disease has been hypothesized. The aim of this work was to assess whether human herpesvirus (HHV)‐6 and HHV‐8, two DNA viruses with a distinct tropism for endothelium and lymphocytes, may be associated with coronary instability. An age‐ and gender‐matched cross‐sectional study was undertaken in 70 patients with testing of plasma HHV‐6 and HHV‐8 DNA load in different cardiovascular clinical settings: 29 patients with acute myocardial infarction, 21 patients with stable coronary artery disease, and 20 patients without coronary and carotid artery atherosclerosis subjected to cardiac valve replacement. In all patients, HHV‐6 and HHV‐8 plasma DNA was tested by using highly sensitive, calibrated quantitative real‐time PCR assays which employ a synthetic DNA calibrator to adjust for DNA extraction and amplification efficiency. HHV‐8 viremia was undetectable in all three groups. HHV‐6 viremia was detected in a substantial fraction of the samples examined (18.6%) without significant differences among the three groups (ST segment elevation myocardial infarction: 17.2%; stable coronary artery disease: 14.3%; patients without coronary and carotid artery atherosclerosis: 25%). Furthermore, no significant differences in plasma HHV‐6 load were observed amongst the three groups of patients. These findings indicate that coronary instability is not associated specifically with active HHV‐6 or HHV‐8 infection. However, an unusually high rate of active HHV‐6 infection was documented among patients without atherosclerosis admitted to hospital with cardiac disease. J. Med. Virol. 84:1961–1966, 2012.

Reduction of mitral valve regurgitation caused by acute papillary muscle ischemia

Background A 67-year-old man was admitted to a coronary care unit for non-ST-segment elevation myocardial infarction with complicating acute heart failure. Severe mitral regurgitation was detected by echocardiography at presentation. Repeat echocardiography carried out during another ischemic episode revealed a marked reduction in the patients mitral regurgitation that was related to decreased apical traction of the valve leaflets.Investigations Physical examination, electrocardiography, laboratory tests, coronary angiography, chest radiography, echocardiography.Diagnosis Mitral regurgitation associated with acute coronary syndrome.Management Early revascularization by percutaneous coronary intervention, supported by pharmacological therapy to decrease left ventricular filling pressure.

A surprise behind the dark

Standard ultrasound has a poor accuracy in the detection of carotid plaque surface irregularities and ulcers, which are features of vulnerable lesions. Sonographic contrast agents can improve vessel wall lumen definition, thus potentially overcoming this limitation. Recent studies also suggest that contrast ultrasound can be used to study intraplaque neovascularizaion, a potential marker of high-risk lesions. This case represents a striking example of the added value of contrast ultrasound to improve diagnostic accuracy of vascular studies, particularly in the detection of plaque surface irregularities and plaque neovascularization.

Not So Mural Thrombus

A 64-year-old man with type 2 diabetes mellitus was admitted to our emergency department for a 12-hour history of waxing and waning chest pain. During the first hour of observation, he complained about a new episode of chest pain accompanied by ST elevation in leads V2 and V3. The patient underwent emergency coronary angiography that showed 80% stenosis of the proximal left anterior descending artery with subocclusive thrombotic lesion …