In-Vivo Assessment of Coronary Atherosclerosis

Intravascular ultrasound (IVUS) has emerged as a highly accurate tool for the serial assessment of the natural history of coronary atherosclerosis and to evaluate the effect of different conventional and emerging drug therapies on the progression of atherosclerosis. The contemporary and future application of IVUS is linked to the study of different applications of the analysis of radiofrequency data, both for the improvement of plaque characterization and for the assessment of mechanical properties of plaques. Overall, such insightful analysis of the radiofrequency data might potentially aid the detection of plaques with allegedly high-risk characteristics and monitor their natural history in prospective natural history studies. This thesis provides important data regarding the internal and external validation of spectral analysis of radiofrequency data for the assessment of plaque composition in vivo

In-vivo, cardiac-cycle related intimal displacement of coronary plaques assessed by 3-D ECG-gated intravascular ultrasound: Exploring its correlate with tissue deformability identified by palpography

Background: ECG-gated image acquisition of intravascular ultrasound (IVUS) has been shown to provide more accurate measurements at different phases of the cardiac cycle. Objective: We sought to explore the ability dynamic assessment of ECG-gated 3-D IVUS to identify deformable regions of coronary plaques, by testing the hypothesis that at a given pressure and region, a faster displacement of the intima would correspond to high strain (soft tissue) regions assessed by palpography. Methods: ECG-gated 3-D IVUS and palpograms were acquired using 30 and 20 MHz IVUS imaging catheters respectively. Frames with high and/or low strain spots identified by palpography were randomly selected and the spots were assigned to a respective quadrant within the cross section. A color-blinded side-by-side view was performed to enable the co-localization of the same region. Subsequently, the pressure driven displacement of the intima was established for each quadrant and a binary score (significant displacement or no displacement) was decided. Results: One hundred and twenty-four quadrants were studied and the prevalence of highly deformable quadrants was low (n=7, 5.6% of the total). The sensitivity, specificity, positive predictive value and negative predictive value of 3-D ECG-gated IVUS to detect deformable quadrants as assessed by palpography were 42.9, 87.2, 16.7, and 96.2% respectively. Conclusion: In this pilot in vivo study, the intimal displacement velocity in the radial direction assessed by gray-scale 3-D ECG-gated IVUS failed to correlate with highly deformable regions. However, these preliminary findings suggest that the absence of significant displacement of the intima might be accurate to predict the absence of deformable tissue

In vivo variability in quantitative coronary ultrasound and tissue characterization measurements with mechanical and phased-array catheters

Background: Both mechanical and phased-array catheters are used in clinical trials to assess quantitative parameters. Only limited evaluation of the in vivo agreement of volumetrical measurements between such systems has been performed, despite the fact that such information is essential for the conduction of atherosclerosis regression trials. Methods and results: We prospectively evaluated the agreement in morphometric measurements and intravascular ultrasound (IVUS)-based plaque characterization between a 40 MHz rotating transducer (3.2 F Atlantis, Boston Scientific Corp.) and a 20 MHz phased-array catheter (2.9 F Eagle Eye, Volcano Therapeutics, Rancho Cordova, California) in 16 patients. Lumen (7.3 ± 2.0 mm2 vs. 6.7 ± 1.8 mm2, p = 0.001) and vessel (11.8 ± 3.3 mm2 vs. 11.0 ± 2.9 mm2, p = 0.02) cross-sectional areas (CSA) were significantly greater with the 20 MHz system. Plaque CSA measurements showed no significant difference between systems (4.4 ± 2.3 mm2 vs. 4.4 ± 2.1). The relative differences were less than 10% for the three variables. On IVUS-based tissue characterization (13 patients), calculated percentage hypoechogenic volume was significantly higher for the 20 MHz system (96.7 ± 2.38 vs. 88.4 ± 5.53, p < 0.0001). Conclusions: Quantitative IVUS analyses display significant catheter type-dependent variability. It is unclear whether the variability reflects overestimation of measurements with the phased-array or underestimation with the mechanical system. Although plaque burden measurements did not differ significantly between systems, it appears prudent to recommend the use of a single system for progression/ regression studies

Positive remodeling at 3 year follow up is associated with plaque free coronary wall segment at baseline: A serial IVUS study

At present it is unknown what limits the arterial remodeling process during atherosclerotic plaque formation. In healthy arteries remodeling is regulated by the shear stress induced response by the endothelium. As endothelium at the plaque site is assumed to be dysfunctional, we tested the hypothesis that plaque free wall (PFW) determines vascular remodeling during atherosclerotic plaque build-up. Methods & results: 66 human coronary ROIs (38 patients) were studied at baseline and at 3 years follow up applying intravascular ultrasound (IVUS). From the IVUS images the lumen and external elastic membrane contours were delineated to assess wall thickness (WT), vessel area (VA), Plaque Area (PA) and plaque burden (PA/VA*100%). WT5%. At baseline, IVUS-PFW was inversely related to plaque burden (p180° (i.e. larger than half of the circumference) compared to PFW180° at baseline had the largest change in VA (1.1±2.1 vs.-0.4±0.6mm2, p180 at baseline had the highest probability to undergo positive remodeling

Reproducibility of intravascular ultrasound radiofrequency data analysis: Implications for the design of longitudinal studies

Objectives: The purpose of this study was to assess in vivo the reproducibility of tissue characterization using spectral analysis of intravascular ultrasound (IVUS) radiofrequency data (IVUS-VH). Background: Despite the need for reproducibility data to design longitudinal studies, such information remains unexplored. Methods and results: IVUS-VH (Volcano Corp., Rancho Cordova, USA) was performed in patients referred for elective percutaneous intervention and in whom a non-intervened vessel was judged suitable for a safe IVUS interrogation. The IVUS catheters used were commercially available catheters (20 MHz, Volcano Corp., Rancho Cordova, USA). Following IVUS-VH acquisition, and after the disengagement and re-engagement of the guiding catheter, an additional acquisition was performed using a new IVUS catheter. Fifteen patients with 16 non-significant lesions were assessed by 2 independent observers. The relative inter-catheter differences regarding geometrical measurements were negligible for both observers. The inter-catheter relative difference in plaque cross-sectional area (CSA) was 3.2% for observer 1 and 0.5% for observer 2. The limits of agreement for (observer 1 measurements) lumen, vessel, plaque and plaque burden measurements were 0.82, -1.10 mm 2;0.80, -0.66 mm2;1.08, -0.66 mm2; and 5.83, -3.89%; respectively. Limits of agreement for calcium, fibrous, fibrolipidic and necrotic core CSA measurements were 0.22, -0.25 mm2;1.02, -0.71 mm2;0.61, -0.65 mm2; and 0.43, -0.38 mm2 respectively. Regarding the inter-observer agreement, the limits of agreement for lumen, vessel, plaque and plaque burden measurements were 2.61, -2.09 mm2;2.20-3.03 mm2;1.70, -3.04 mm2; and 9.16, -16.41%; respectively, and for calcium, fibrous, fibrolipidic and necrotic core measurements of 0.08, -0.09 mm2;0.89, -1.28 mm2;0.74, -1.06 mm2; and 0.16, -0.20 mm2; respectively. Conclusions: The present study demonstrates that the geometrical and compositional output of IVUS-VH is acceptably reproducible

[Emergent strategies in interventional cardiology]

Despite the advances in the treatment of patients with coronary artery disease, sudden cardiac death is still unacceptably prevalent. Patients with ischemic heart disease usually require a combination of therapies (drugs and coronary intervention) and may continue to experience symptoms. Recently, numerous percutaneous interventional treatments and diagnostic tools have been developed to diagnose the vulnerable plaque and to treat the large number of patients with myocardial ischemia. Ongoing research on the use of drug eluting stents, catheter based bypass graft (percutane

[New insights towards catheter-based identification of vulnerable plaque]

Sudden cardiac death or unheralded acute coronary syndromes are common initial manifestations of coronary atherosclerosis and most such events occur at sites of non-flow limiting coronary atherosclerosis. Autopsy data suggests that plaque composition is a key determinant of the propensity of atherosclerotic lesions to provoke clinical events. Most of these events are related to plaque rupture and subsequent thrombotic occlusion at the site of non-flow limiting atherosclerotic lesions in epicardial coronary arteries. Detection of these non-obstructive, lipid rich, high-risk plaques may have an important impact on the prevention of acute myocardial infarction and sudden death. Currently, there are several intravascular tools capable of locally evaluating determinants of plaque vulnerability such as the size of the lipid core, thickness of the fibrous cap, inflammation within the cap and positive remodeling. These new modalities have the potential to provide insights into the pathophysiology of the natural history of coronary plaque by means of prospective studies

Prevalence and characteristics of major and minor coronary artery anomalies in an adult population assessed by computed tomography coronary angiography

Aims: There is conflicting data regarding the prevalence and characteristics of coronary artery anomalies (CAAs). We sought to explore the prevalence and characteristics of major and minor CAAs using computed tomography coronary angiography (CCTA). Methods and results: We prospectively studied 577 patients in sinus rhythm referred for control of stents or for screening due to the presence of multiple risk factors (53%), or due to chest pain, equivalent symptoms or inconclusive stress tests (47%). 40 and 64 slice CT scanners were used. The mean age was 61±11 years and 81% were male. We identified CAAs in 121 (21.0%) patients. Anomalous origination of a coronary artery from the opposite sinus (ACAOS) were identified in 6/577 (1%) patients. Coronary ectasia or aneurysm was present in 10/577 (1.7%) patients. One-hundred and nine intramuscular segments (MB) were found in 100/577 (17.3%) patients. Coronary hypoplasia was identified in 3/577 (0.5%) patients, all involving the RCA, and 3/577 (0.5%) patients had an absent left main coronary artery. None of the segments with ACAOS (proximal segment) or MB had atherosclerotic plaque. Conclusions: CAAs were highly prevalent along the coronary tree and anatomical characteristics that might help stratify the risk and guide therapy of CAAs could be easily identified with CCTA

EFFECT OF PERINDOPRIL ON CORONARY REMODELLING: INSIGHTS FROM A MULTICENTRE, RANDOMIZED STUDY.

Aims This study sought to evaluate the effect of perindopril in coronary remodelling. Methods and results In this sub-study of a double-blind, multicentre trial, patients without clinical evidence of heart failure were randomized to perindopril 8 mg/day or placebo for at least 3 years and IVUS investigation was performed at both time-points. Positive and negative remodelling were defined as a relative increase (positive remodelling) or decrease (negative remodelling) of the mean vessel crosssectional area (CSA) .2 SD of the mean intra-observer difference. A total of 118 matched evaluable IVUS (711 matched 5 mm segments) were available at follow-up. After a median follow-up of 3.0 (inter-quartile range 1.9, 4.1) years, there was no significant difference in the change of plaque CSA between perindopril (360 segments) and placebo (351 segments) groups, P ¼ 0.27. Conversely, the change in vessel CSA was significantly different between groups (perindopril 20.18+2.4 mm2 vs. placebo 0.19+2.4, P ¼ 0.04). Negative remodelling occurred more frequently in the perindopril than in the placebo group (34 vs. 25%, P ¼ 0.01). In addition, the placebo group showed a larger, although not significant, mean remodelling index (RI) than the perindopril group (1.03+0.2 vs. 1.00+0.2, P ¼ 0.06). The temporal change in vessel dimensions assessed by the RI was significantly correlated with the change in plaque dimensions (r ¼ 0.48, P , 0.0001). Conclusion In this sub-analysis of a multicentre, controlled study, long-term administration of perindopril was associated with a constrictive remodelling pattern without affecting the lumen

Long-term safety and efficacy of percutaneous coronary intervention with stenting and coronary artery bypass surgery for multivessel coronary artery disease: A meta-analysis with 5-year patient-level data from the ARTS, ERACI-II, MASS-II, and SoS trials

Background - Randomized trials that studied clinical outcomes after percutaneous coronary intervention (PCI) with bare metal stenting versus coronary artery bypass grafting (CABG) are underpowered to properly assess safety end points like death, stroke, and myocardi