Heterogeneity of Plaque Structural Stress Is Increased in Plaques Leading to MACE: Insights From the PROSPECT Study.

OBJECTIVES: This study sought to determine if plaque structural stress (PSS) and other plaque stress parameters are increased in plaques that cause future major adverse cardiovascular event(s) (MACE) and if incorporating these parameters improves predictive capability of intravascular ultrasonography (IVUS). BACKGROUND: Less than 10% of coronary plaques identified as high-risk by intravascular imaging result in subsequent MACE. Thus, more specific measurements of plaque vulnerability are required for effective risk stratification. METHODS: Propensity score matching in the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study plaque cohort resulted in 35 nonculprit lesions (NCL) associated with future MACE and 66 matched NCL that remained clinically silent. PSS was calculated by finite element analysis as the mechanical loading within the plaque structure in the periluminal region. RESULTS: PSS was increased in the minimal luminal area (MLA) regions of NCL MACE versus no MACE plaques for all plaques (PSS: 112.1 ± 5.5 kPa vs. 90.4 ± 3.3 kPa, respectively; p = 0.001) and virtual histology thin-cap fibroatheromas (VH-TCFAs) (PSS: 119.2 ± 6.6 kPa vs. 95.8 ± 5.0 kPa, respectively; p = 0.005). However, PSS was heterogeneous over short segments, and PSS heterogeneity index (HI) was markedly greater in NCL MACE than in no-MACE VH-TCFAs (HI: 0.43 ± 0.05 vs. 0.29 ± 0.03, respectively; p = 0.01). Inclusion of PSS in plaque assessment improved the identification of NCLs that led to MACE, including in VH-TCFAs (p = 0.03) and plaques with MLA ≤4 mm2 (p = 0.03). Incorporation of an HI further improved the ability of PSS to identify MACE NCLs in a variety of plaque subtypes including VH-TCFA (p = 0.001) and plaques with MLA ≤4 mm2 (p = 0.002). CONCLUSIONS: PSS and variations in PSS are increased in the peri-MLA regions of plaques that lead to MACE. Moreover, longitudinal heterogeneity in PSS is markedly increased in MACE plaques, especially VH-TCFAs, potentially predisposing to plaque rupture. Incorporation of PSS and heterogeneity in PSS may improve the ability of IVUS to predict MACE.BH

Plaque Rupture in Coronary Atherosclerosis Is Associated With Increased Plaque Structural Stress.

OBJECTIVES: The aim of this study was to identify the determinants of plaque structural stress (PSS) and the relationship between PSS and plaques with rupture. BACKGROUND: Plaque rupture is the most common cause of myocardial infarction, occurring particularly in higher risk lesions such as fibroatheromas. However, prospective intravascular ultrasound-virtual histology studies indicate that 135 kPa was a good predictor of rupture in higher risk regions. CONCLUSIONS: PSS is determined by plaque composition, plaque architecture, and lumen geometry. PSS and PSS variability are increased in plaques with rupture, particularly at proximal segments. Incorporating PSS into plaque assessment may improve identification of rupture-prone plaques.This work was supported by British Heart Foundation grants CH/20000003/12800, FS/13/33/30168, and FS/15/26/31441; Heart Research UK grant RG2638/14/16 and MRC Confidence in Concepts award; and the NIHR Cambridge Biomedical Research Centre

Plaque rupture in coronary atherosclerosis is associated with increased plaque structural stress

OBJECTIVES: The aim of this study was to identify the determinants of plaque structural stress (PSS) and the relationship between PSS and plaques with rupture. BACKGROUND: Plaque rupture is the most common cause of myocardial infarction, occurring particularly in higher risk lesions such as fibroatheromas. However, prospective intravascular ultrasound–virtual histology studies indicate that 135 kPa was a good predictor of rupture in higher risk regions. CONCLUSIONS: PSS is determined by plaque composition, plaque architecture, and lumen geometry. PSS and PSS variability are increased in plaques with rupture, particularly at proximal segments. Incorporating PSS into plaque assessment may improve identification of rupture-prone plaques

VH-IVUS and OCT identification of TCFA

BACKGROUND: Although rupture of thin-cap fibroatheroma (TCFA) underlies most myocardial infarctions, reliable TCFA identification remains challenging. Virtual-histology intravascular ultrasound (VH-IVUS) and optical coherence tomography (OCT) can assess tissue composition and classify plaques. However, direct comparisons between VH-IVUS and OCT are lacking and it remains unknown whether combining these modalities improves TCFA identification. METHODS AND RESULTS: Two hundred fifty-eight regions-of-interest were obtained from autopsied human hearts, with plaque composition and classification assessed by histology and compared with coregistered ex vivo VH-IVUS and OCT. Sixty-seven regions-of-interest were classified as fibroatheroma on histology, with 22 meeting criteria for TCFA. On VH-IVUS, plaque (10.91±4.82 versus 8.42±4.57 mm(2); P=0.01) and necrotic core areas (1.59±0.99 versus 1.03±0.85 mm(2); P=0.02) were increased in TCFA versus other fibroatheroma. On OCT, although minimal fibrous cap thickness was similar (71.8±44.1 μm versus 72.6±32.4; P=0.30), the number of continuous frames with fibrous cap thickness ≤85 μm was higher in TCFA (6.5 [1.75-11.0] versus 2.0 [0.0-7.0]; P=0.03). Maximum lipid arc on OCT was an excellent discriminator of fibroatheroma (area under the curve, 0.92; 95% confidence interval, 0.87-0.97) and TCFA (area under the curve, 0.86; 95% confidence interval, 0.81-0.92), with lipid arc ≥80° the optimal cut-off value. Using existing criteria, the sensitivity, specificity, and diagnostic accuracy for TCFA identification was 63.6%, 78.1%, and 76.5% for VH-IVUS and 72.7%, 79.8%, and 79.0% for OCT. Combining VH-defined fibroatheroma and fibrous cap thickness ≤85 μm over 3 continuous frames improved TCFA identification, with diagnostic accuracy of 89.0%. CONCLUSIONS: Both VH-IVUS and OCT can reliably identify TCFA, although OCT accuracy may be improved using lipid arc ≥80° and fibrous cap thickness ≤85 μm over 3 continuous frames. Combined VH-IVUS/OCT imaging markedly improved TCFA identification.This study was funded by grants from the British Heart Foundation (FS/13/33/30168), Heart Research UK (RG2638/14/16), the Cambridge NIHR Biomedical Research Centre, and the BHF Cambridge Centre for Research Excellence.This is the final version of the article. It first appeared from American Heart Association via http://dx.doi.org/10.1161/CIRCIMAGING.115.00348

Leo Strauss and International Relations: The politics of modernity's abyss

This article argues that an engagement with the political philosophy of Leo Strauss is of considerable value in International Relations (IR), in relation to the study of both recent US foreign policy and contemporary IR theory. The question of Straussian activities within and close to the foreign policy-making establishment in the United States during the period leading up to the 2003 invasion of Iraq has been the focus of significant scholarly and popular attention in recent years. This article makes the case that several individuals influenced by Strauss exercised considerable influence in the fields of intelligence production, the media and think tanks, and traces the ways in which elements of Strauss’ thought are discernible in their interventions in these spheres. It further argues that Strauss’ political philosophy is of broader significance for IR insofar as it can be read as a securitising response to the dangers he associated with the foundationlessness of the modern condition. The article demonstrates that the politics of this response are of crucial importance for contemporary debates between traditional and critical IR theorists

Molecular imaging of angiogenesis with SPECT

Single-photon emission computed tomography (SPECT) and position emission tomography (PET) are the two main imaging modalities in nuclear medicine. SPECT imaging is more widely available than PET imaging and the radionuclides used for SPECT are easier to prepare and usually have a longer half-life than those used for PET. In addition, SPECT is a less expensive technique than PET. Commonly used gamma emitters are: 99mTc (Emax 141 keV, T1/2 6.02 h), 123I (Emax 529 keV, T1/2 13.0 h) and 111In (Emax 245 keV, T1/2 67.2 h). Compared to clinical SPECT, PET has a higher spatial resolution and the possibility to more accurately estimate the in vivo concentration of a tracer. In preclinical imaging, the situation is quite different. The resolution of microSPECT cameras (<0.5 mm) is higher than that of microPET cameras (>1.5 mm). In this report, studies on new radiolabelled tracers for SPECT imaging of angiogenesis in tumours are reviewed