A quantitative coronary angiography-matched comparison between a prospective randomised multicentre cutting balloon angioplasty and bare metal stent trial (REDUCE III) and the Rapamycin-Eluting Stent Evaluation At Rotterdam Cardiology Hospital (RESEARCH) study

Aims: There remains significant concern about the long-term safety of drug-eluting stents (DES). However, bare metal stents (BMS) have been used safely for over two decades. There is therefore a pressing need to explore alternative strategies for reducing restenosis with BMS. This study was designed to examine whether IVUS-guided cutting balloon angioplasty (CBA) with BMS could convey similar restenosis rates to DES. Methods and results: In the randomised REstenosis reDUction by Cutting balloon angioplasty Evaluation (REDUCE III) study, 521 patients were divided into four groups based on device and IVUS use before BMS (IVUS-CBA-BMS: 137 patients; Angio-CBA-BMS: 123; IVUS-BA-BMS: 142; and Angio-BA-BMS: 119). At follow-up, the IVUS-CBA-BMS group had a significantly lower restenosis rate (6.6%) than the other groups (p=0.016). We performed a quantitative coronary angiography (QCA) based matched comparison between an IVUS-guided CBA-BMS strategy (REDUCE III) and a DES strategy (Rapamycin-Eluting-Stent Evaluation At Rotterdam Cardiology. Hospital, the RESEARCH study). We matched the presence of diabetes, vessel size, and lesion severity by QCA. Restenosis (>50% diameter stenosis at follow-up) and target vessel revascularisation (TVR) were examined. QCA-matched comparison resulted in 120-paired lesions. While acute gain was significantly greater in IVUS-CBA-BMS than DES (1.65 +/- 0.41 mm vs. 1.28 +/- 0.57 mm, p=0.001), late loss was significantly less with DES than with IVUS-CBA-BMS (0.03 +/- 0.42 mm vs. 0.80 +/- 0.47 mm, p=0.001). However, no difference was found in restenosis rates (IVUS-CBA-BMS: 6.6% vs. DES: 5.0%, p=0.582) and TVR (6.6% and 6.6%, respectively). Conclusions: An IVUS-guided CBA-BMS strategy yielded restenosis rates similar to those achieved by DES and provided an effective alternative to the use of DES.

Relation between visceral fat and coronary artery disease evaluated by multidetector computed tomography

Visceral abdominal fat has been associated to cardiovascular risk factors and coronary artery disease (CAD). Computed tomography (CT) coronary angiography is an emerging technology allowing detection of both obstructive and nonobstructive CAD adding information to clinical risk strati. cation. The aim of this study was to evaluate the association between CAD and adiposity measurements assessed clinically and by CT. We prospectively evaluated 125 consecutive subjects (57% men, age 56.0 +/- 12 years) referred to perform CT angiography. Clinical and laboratory variables were determined and CT angiography and abdominal CT were performed in a 64-slice scanner. CAD was defined as any plaque calcified or not detected by CT angiography. Visceral and subcutaneous adiposity areas were determined at different intervertebral levels. CT angiography detected CAD in 70 (56%) subjects, and no association was found with usual anthropometric adiposity measurements (waist and hip circumferences and body mass index). Otherwise, CT visceral fat areas (VFA) were significantly related to CAD. VFA T12-L1 values >= 145 cm(2) had an odds ratio of 2.85 (95% CI 1.30-6.26) and VFA L4-L5 >= 150 cm(2) had a 2.87-fold (95% CI 1.31-6.30) CAD risk. The multivariate analysis determined age and VFA T12-L1 as the only independent variables associated to CAD. Visceral fat assessed by CT is an independent marker of CAD determined by CT angiography. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Polymorphisms of the renin-angiotensin system in patients with multifocal renal arterial fibromuscular dysplasia

Fibromuscular dysplasia (FMD) is an important cause of renal artery stenosis, particularly in young females. Polymorphisms of the renin-angiotensin (RA) system have been implicated in the pathogenesis of hypertension and atherosclerotic vascular disease, and may play a role in the development of FMD. Examination of polymorphisms by PCR for angiotensin-converting enzyme (ACE) I/D, angiotensin II type 1 receptor (AT(1)R) A1166C and angiotensinogen (AGT) M235T and T174M was undertaken in 43 patients with typical multifocal renal arterial FMD (MF-FMD) and in 89 controls. The age of NIF-FMD patients at the time of diagnosis of hypertension did not differ (38.6 + 11.1 years vs 35.5 +/- 10.3 years, P = 0.12) from controls and the proportion (95% vs 86%, P = 0.14) of females was similar. Allele frequencies did not differ significantly between groups, except that MF-FMD patients had a significantly higher frequency of the ACE I allele than control subjects (0.62 vs 0.47, P = 0.026). Since the ACE I allele is associated with lower circulating ACE levels and possibly lower tissue levels of angiotensin II (Ang II), and since Ang II modulates vascular smooth muscle cell growth and synthetic activity, the I allele might predispose to defective remodelling of the arterial media, and thus to the development of MF-FMD. This contrasts with atherosclerotic renal artery stenosis, coronary stent restenosis and carotid intimal thickening, which are diseases affecting the arterial intima, and which are associated with increased frequency of the D allele.

The influence of geometric factors on the wall shear stress distribution in realistic human coronary arteries

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para a obtenção do grau de Mestre em Engenharia Biomédica. A presente dissertação foi desenvolvida no Erasmus Medical Center em Roterdão, Holanda

Comparison between MDCT and Grayscale IVUS in a Quantitative Analysis of Coronary Lumen in Segments with or without Atherosclerotic Plaques

Background: The diagnostic accuracy of 64-slice MDCT in comparison with IVUS has been poorly described and is mainly restricted to reports analyzing segments with documented atherosclerotic plaques. Objectives: We compared 64-slice multidetector computed tomography (MDCT) with gray scale intravascular ultrasound (IVUS) for the evaluation of coronary lumen dimensions in the context of a comprehensive analysis, including segments with absent or mild disease. Methods: The 64-slice MDCT was performed within 72 h before the IVUS imaging, which was obtained for at least one coronary, regardless of the presence of luminal stenosis at angiography. A total of 21 patients were included, with 70 imaged vessels (total length 114.6 ± 38.3 mm per patient). A coronary plaque was diagnosed in segments with plaque burden > 40%. Results: At patient, vessel, and segment levels, average lumen area, minimal lumen area, and minimal lumen diameter were highly correlated between IVUS and 64-slice MDCT (p < 0.01). However, 64-slice MDCT tended to underestimate the lumen size with a relatively wide dispersion of the differences. The comparison between 64-slice MDCT and IVUS lumen measurements was not substantially affected by the presence or absence of an underlying plaque. In addition, 64-slice MDCT showed good global accuracy for the detection of IVUS parameters associated with flow-limiting lesions. Conclusions: In a comprehensive, multi-territory, and whole-artery analysis, the assessment of coronary lumen by 64-slice MDCT compared with coronary IVUS showed a good overall diagnostic ability, regardless of the presence or absence of underlying atherosclerotic plaques.

Association between LDL-C, Non HDL-C, and Apolipoprotein B Levels with Coronary Plaque Regression

Background:Previous reports have inferred a linear relationship between LDL-C and changes in coronary plaque volume (CPV) measured by intravascular ultrasound. However, these publications included a small number of studies and did not explore other lipid markers.Objective:To assess the association between changes in lipid markers and regression of CPV using published data.Methods:We collected data from the control, placebo and intervention arms in studies that compared the effect of lipidlowering treatments on CPV, and from the placebo and control arms in studies that tested drugs that did not affect lipids. Baseline and final measurements of plaque volume, expressed in mm3, were extracted and the percentage changes after the interventions were calculated. Performing three linear regression analyses, we assessed the relationship between percentage and absolute changes in lipid markers and percentage variations in CPV.Results:Twenty-seven studies were selected. Correlations between percentage changes in LDL-C, non-HDL-C, and apolipoprotein B (ApoB) and percentage changes in CPV were moderate (r = 0.48, r = 0.47, and r = 0.44, respectively). Correlations between absolute differences in LDL-C, non‑HDL-C, and ApoB with percentage differences in CPV were stronger (r = 0.57, r = 0.52, and r = 0.79). The linear regression model showed a statistically significant association between a reduction in lipid markers and regression of plaque volume.Conclusion:A significant association between changes in different atherogenic particles and regression of CPV was observed. The absolute reduction in ApoB showed the strongest correlation with coronary plaque regression.

A Novel Algorithm to Quantify Coronary Remodeling Using Inferred Normal Dimensions

Background:Vascular remodeling, the dynamic dimensional change in face of stress, can assume different directions as well as magnitudes in atherosclerotic disease. Classical measurements rely on reference to segments at a distance, risking inappropriate comparison between dislike vessel portions.Objective:to explore a new method for quantifying vessel remodeling, based on the comparison between a given target segment and its inferred normal dimensions.Methods:Geometric parameters and plaque composition were determined in 67 patients using three-vessel intravascular ultrasound with virtual histology (IVUS-VH). Coronary vessel remodeling at cross-section (n = 27.639) and lesion (n = 618) levels was assessed using classical metrics and a novel analytic algorithm based on the fractional vessel remodeling index (FVRI), which quantifies the total change in arterial wall dimensions related to the estimated normal dimension of the vessel. A prediction model was built to estimate the normal dimension of the vessel for calculation of FVRI.Results:According to the new algorithm, “Ectatic” remodeling pattern was least common, “Complete compensatory” remodeling was present in approximately half of the instances, and “Negative” and “Incomplete compensatory” remodeling types were detected in the remaining. Compared to a traditional diagnostic scheme, FVRI-based classification seemed to better discriminate plaque composition by IVUS-VH.Conclusion:Quantitative assessment of coronary remodeling using target segment dimensions offers a promising approach to evaluate the vessel response to plaque growth/regression.

Endovascular thoracic aortic aneurysm repair without angiography.

OBJECTIVE: : Intravascular ultrasound (IVUS) generates high definition circumferential cross-sectional images and provides real-time readout of vascular dimensions, including visualization of vessel branches. We have used it as an alternative to angiography in the endovascular thoracic aneurysm repair work-up. METHODS: : Out of consecutive 203 patients with descending thoracic aortic aneurysm, 89 (43.8%) received endovascular treatment [mean age, 68 ± 8 years; range, 29-82; male, 79 (88.7%); female, 10 (11.3%)] without using angiography during the endovascular procedure. IVUS (6 F, 12.5 MHz probe or 10 F 9 MHz) coupled with fluoroscopy for the placement of radiopaque markers was used for target site identification, landing zone measurement, device positioning, and assessment of endovascular repair. RESULTS: : Hospital mortality was 4/89 (4.5%). Number of devices implanted in each patient was 1.2 (range, 1-3). X-ray exposure time was 12 ± 8 minutes. Median procedure time was 63 ± 20 minutes. Conversion to open surgery was necessary in one patient (1.1%) because of aortic dissection. In nine patients (10.1%) left subclavian artery was covered because of a short neck. Two patients (2.2%) had vascular access lesions and required surgical repair. One patient developed paraplegia (1.1%). Early endoleak was observed in eight patients (8.9%) and 4 (4.5%) required additional procedures (proximal or distal extensions). Late conversion was necessary in one patient (1.1%). CONCLUSIONS: : IVUS provides all information necessary for device selection, target site identification as well as safe and correct deployment of thoracic endoprostheses and makes periprocedural angiography unnecessary, thus avoiding the risk of renal failure because of contrast medium.

Assessment of coronary stenosis, plaque burden and remodeling by multidetector computed tomography in patients referred for suspected coronary artery disease.

Aims To compare multidetector computed tomography (MDCT) with intravascular ultrasound (IVUS) and invasive quantitative coronary angiography (QCA) for assessment of coronary lesions in patients referred for suspected coronary artery disease (CAD). Methods and results We studied 57 patients (48 men; mean age: 63 +/- 10 years) who underwent 64-slice MDCT because of atypical chest pain, stable angina, or ECG abnormalities and were diagnosed with CAD. All patients subsequently underwent QCA and IVUS. We analyzed 102 coronary lesions using the three techniques. Measurements of luminal area stenosis and cross-sectional area by MDCT (72.9 +/- 7.0% and 4.5 +/- 1.8 mm(2), respectively) were in good agreement with those by IVUS [72.7 +/- 6.7% and 4.5 +/- 1.6 mm(2), respectively; Lin's concordance correlation coefficient r = 0.847; 95% confidence interval (CI) = 0.792-0.902 and r = 0.931; 95% CI = 0.906-0.956, respectively] but not QCA (r = 0.115; 95% CI = 0.040-0.189 and r = 0.433; 95% CI = 0.291-0.576, respectively). Plaque cross-sectional area and plaque volume measured by MDCT (12.4 +/- 3.8 mm(2) and 104.7 +/- 52.8 mu l, respectively) were in good agreement with those by IVUS (12.2 +/- 3.7 mm(2) and 102.8 +/- 54.1 mu l; r = 0.913; 95% CI = 0.880-0.945 and r = 0.979; 95% CI = 0.969-0.990, respectively). Remodeling index measurements by MDCT (1.22 +/- 0.22) were in good agreement with those by IVUS (r = 0.876; 95% CI = 0.831-0.922). Positive remodeling occurred in 63% of stenoses. Conclusion MDCT allows accurate noninvasive assessment of coronary stenosis, plaque burden and remodeling in patients referred for suspected CAD. Positive remodeling is a frequent finding in stable lesions. J Cardiovasc Med 12:122-130 (C) 2011 Italian Federation of Cardiology.

Total aortic arch stenting--hemodynamical impact of carotid artery perfusion.

The aim of this experimental study is to evaluate the feasibility and the outcome of total endovascular stent implantation in the aortic arch. Indications for this operation-technique would be acute or chronic dissection of the aortic arch (non-A-non-B dissection) or type B dissection with retrograde extension. Four pigs were canulated via the distal abdominal aorta and a retrograde placement of a Djumbodis arch stent (4-9 cm) was controlled by using intravascular ultrasound and intracardiac ultrasound by the inferior cava vein and under radioscopic control. Cerebral perfusion, by using a flow meter placed on one prepared carotid artery, were controlled before, immediate post-procedural (<1 min), and in the early follow-up after aortic arch stent implantation. During the implantation process, especially during balloon inflation and deflation, mean carotid perfusion decreases slightly. A reactive increase of carotid perfusion after stent placements indicates transitory cerebral hypo-perfusion. Non-covered aortic arch stent implantation is technically feasible and could be a potential treatment option in otherwise inoperable arch dissections. The time required for balloon inflation and deflation causes an important risk of cerebral ischemia. The latter can be reduced by transaxillary perfusion.

Edge vascular response after polymer-free vs. polymer-based paclitaxel-eluting stent implantation.

BACKGROUND It is unknown if lack of polymer can provoke a different edge response in drug-eluting stents. The aim of this study was to compare edge vascular response between polymer-free paclitaxel-eluting stent (PF-PES) and polymer-based paclitaxel-eluting stents (PB-PES). METHODS AND RESULTS: A total of 165 eligible patients undergoing percutaneous coronary intervention were prospectively randomized 1:1 to receive either PF-PES or PB-PES. Those patients with paired intravascular ultrasound (IVUS) after procedure and at 9-month follow-up were included in this analysis.Seventy-six patients with 84 lesions, divided into PB-PES (38 patients, 41 lesions) and PF-PES groups (38 patients, 43 lesions) had paired post-procedure and 9-month follow-up IVUS and were therefore included in this substudy. There was a significant lumen decrease at the proximal edge of PF-PES (from 9.02±3.06 mm(2)to 8.47±3.05 mm(2); P=0.040), and a significant plaque increase at the distal edges of PF-PES (from 4.39±2.73 mm(2)to 4.78±2.63 mm(2); P=0.004). At the distal edge there was a significant plaque increase in the PF-PES compared to PB-PES (+8.0% vs. -0.6%, respectively; P=0.015) with subsequent lumen reduction (-5.2% vs. +6.0%, respectively; P=0.024). CONCLUSIONS PF-PES had significant plaque increase and lumen reduction at the distal edge as compared to PB-PES, probably due to difference in polymer-based drug-release kinetics between the 2 platforms.

Noninvasive coronary vessel wall and plaque imaging with magnetic resonance imaging.

BACKGROUND: Conventional x-ray angiography frequently underestimates the true burden of atherosclerosis. Although intravascular ultrasound allows for imaging of coronary plaque, this invasive technique is inappropriate for screening or serial examinations. We therefore sought to develop a noninvasive free-breathing MR technique for coronary vessel wall imaging. We hypothesized that such an approach would allow for in vivo imaging of coronary atherosclerosis. METHODS AND RESULTS: Ten subjects, including 5 healthy adult volunteers (aged 35+/-17 years, range 19 to 56 years) and 5 patients (aged 60+/-4 years, range 56 to 66 years) with x-ray-confirmed coronary artery disease (CAD), were studied with a T2-weighted, dual-inversion, fast spin-echo MR sequence. Multiple adjacent 5-mm cross-sectional images of the proximal right coronary artery were obtained with an in-plane resolution of 0.5x1.0 mm. A right hemidiaphragmatic navigator was used to facilitate free-breathing MR acquisition. Coronary vessel wall images were readily acquired in all subjects. Both coronary vessel wall thickness (1.5+/-0.2 versus 1.0+/-0.2 mm) and wall area (21.2+/-3.1 versus 13.7+/-4.2 mm(2)) were greater in patients with CAD (both P:<0.02 versus healthy adults). CONCLUSIONS: In vivo free-breathing coronary vessel wall and plaque imaging with MR has been successfully implemented in humans. Coronary wall thickness and wall area were significantly greater in patients with angiographic CAD. The presented technique may have potential applications in patients with known or suspected atherosclerotic CAD or for serial evaluation after pharmacological intervention.

Imaging of the unstable plaque: how far have we got?

Rupture of unstable plaques may lead to myocardial infarction or stroke and is the leading cause of morbidity and mortality in western countries. Thus, there is a clear need for identifying these vulnerable plaques before the rupture occurs. Atherosclerotic plaques are a challenging imaging target as they are small and move rapidly, especially in the coronary tree. Many of the currently available imaging tools for clinical use still provide minimal information about the biological characteristics of plaques, because they are limited with respect to spatial and temporal resolution. Moreover, many of these imaging tools are invasive. The new generation of imaging modalities such as magnetic resonance imaging, nuclear imaging such as positron emission tomography and single photon emission computed tomography, computed tomography, fluorescence imaging, intravascular ultrasound, and optical coherence tomography offer opportunities to overcome some of these limitations. This review discusses the potential of these techniques for imaging the unstable plaque.

Plaque characteristics and arterial remodeling in coronary and peripheral arterial systems.

BACKGROUND: Few studies have examined plaque characteristics among multiple arterial beds in vivo. The purpose of this study was to compare the plaque morphology and arterial remodeling between coronary and peripheral arteries using gray-scale and radiofrequency intravascular ultrasound (IVUS) at clinical presentation. METHODS AND RESULTS: IVUS imaging was performed in 68 patients with coronary and 93 with peripheral artery lesions (29 carotid, 50 renal, and 14 iliac arteries). Plaques were classified as fibroatheroma (VH-FA) (further subclassified as thin-capped [VH-TCFA] and thick-capped [VH-ThCFA]), fibrocalcific plaque (VH-FC) and pathological intimal thickening (VH-PIT). Plaque rupture (13% of coronary, 7% of carotid, 6% of renal, and 7% of iliac arteries; P = NS) and VH-TCFA (37% of coronary, 24% of carotid, 16% of renal, and 7% of iliac arteries; P = 0.02) were observed in all arteries. Compared with coronary arteries, VH-FA was less frequently observed in renal (P < 0.001) and iliac arteries (P < 0.006). Lesions with positive remodeling demonstrated more characteristics of VH-FA in coronary (84% vs. 25%, P < 0.001), carotid (72% vs. 20%, P = 0.001), and renal arteries (42% vs. 4%, P = 0.001) compared with those with intermediate/negative remodeling. There was positive relationship between remodeling index and percent necrotic area in all four arteries. CONCLUSIONS: Atherosclerotic plaque phenotypes were heterogeneous among four different arteries; renal and iliac arteries had more stable phenotypes compared with coronary artery. In contrast, the associations of remodeling pattern with plaque phenotype and composition were similar among the various arterial beds.