Atherosclerotic pattern of coronary myocardial bridging assessed with CT coronary angiography

The aim of our study was to evaluate the atherosclerotic pattern of patients with coronary myocardial bridging (MB) by means of CT Coronary Angiography (CT-CA). 254 consecutive patients (166 male, mean age 58.6 ± 10.3) who underwent 64-slice CT-CA according to current clinical indications were reviewed for the presence of MB and concomitant segmental atherosclerotic pattern. Coronary plaques were assessed in all patients enrolled. 73 patients (29%) presented single (90%) or multiple (10%) MB, frequently (93%) localized in the mid-distal left anterior descending artery. The MB segment was always free of atherosclerosis. Segments proximal to the MB presented: no atherosclerotic disease (n = 37), positive remodeling (n = 23), 50% stenoses (n = 7). Distal segments presented a different atherosclerosis pattern (P < 0.0001): absence of disease (n = 73), no significant lesions (n = 8). No significant differences were found between segments proximal to MB and proximal coronary segments apart from left main trunk. Pattern of atherosclerotic lesions located in segments 6 and 7 significantly differs between patients with MB and patients without MB (P < 0.05). CT-CA is a reliable method to non-invasively demonstrate MB and related atherosclerotic pattern. CT-CA provides new insight regarding atherosclerosis distribution in segments close to MB

Accuracy of dual-source CT coronary angiography: first experience in a high pre-test probability population without heart rate control

The aim of this study was to assess the diagnostic accuracy of dual-source computed tomography (DSCT) for evaluation of coronary artery disease (CAD) in a population with extensive coronary calcifications without heart rate control. Thirty patients (24 male, 6 female, mean age 63.1±11.3 years) with a high pre-test probability of CAD underwent DSCT coronary angiography and invasive coronary angiography (ICA) within 14±9 days. No beta-blockers were administered prior to the scan. Two readers independently assessed image quality of all coronary segments with a diameter ≥1.5 mm using a four-point score (1: excellent to 4: not assessable) and qualitatively assessed significant stenoses as narrowing of the luminal diameter >50%. Causes of false-positive (FP) and false-negative (FN) ratings were assigned to calcifications or motion artifacts. ICA was considered the standard of reference. Mean body mass index was 28.3±3.9 kg/m(2) (range 22.4–36.3 kg/m(2)), mean heart rate during CT was 70.3±14.2 bpm (range 47–102 bpm), and mean Agatston score was 821±904 (range 0–3,110). Image quality was diagnostic (scores 1–3) in 98.6% (414/420) of segments (mean image quality score 1.68±0.75); six segments in three patients were considered not assessable (1.4%). DSCT correctly identified 54 of 56 significant coronary stenoses. Severe calcifications accounted for false ratings in nine segments (eight FP/one FN) and motion artifacts in two segments (one FP/one FN). Overall sensitivity, specificity, positive and negative predictive value for evaluating CAD were 96.4, 97.5, 85.7, and 99.4%, respectively. First experience indicates that DSCT coronary angiography provides high diagnostic accuracy for assessment of CAD in a high pre-test probability population with extensive coronary calcifications and without heart rate control

Is there a gender difference in noninvasive coronary imaging? Multislice computed tomography for noninvasive detection of coronary stenoses

<p>Abstract</p> <p>Background</p> <p>Multislice computed tomography (MSCT) coronary angiography is the foremost alternative to invasive coronary angiography.</p> <p>Methods</p> <p>We sought to compare the diagnostic accuracy of MSCT in female and male patients with suspected coronary disease. Altogether 50 women and 95 men underwent MSCT with 0.5 mm detector collimation. Coronary artery stenoses of at least 50% on conventional coronary angiography were considered significant.</p> <p>Results</p> <p>The coronary vessel diameters of all four main coronary artery branches were significantly larger in men than in women. The diagnostic accuracy of MSCT in identifying patients with coronary artery disease was significantly lower for women (72%) compared with men (89%, <it>p </it>< 0.05). Also sensitivity (70% vs. 95%), positive predictive value (64% vs. 93%), and the rate of nondiagnostic examinations (14% vs. 4%, all: <it>p </it>< 0.05) were significantly worse for women. The effective radiation dose of MSCT coronary angiography was significantly higher in the examination of women (13.7 ± 1.2 mSv) than of men (11.7 ± 0.9 mSv, <it>p </it>< 0.001), mainly as a result of the fact that the radiosensitive female breast (contributing 24.5% of the dose in women) is in the x-ray path.</p> <p>Conclusion</p> <p>Noninvasive coronary angiography with MSCT might be less accurate and sensitive for women than men. Also, women are exposed to a significantly higher effective radiation dose than men.</p

Multi-Organ Expression Profiling Uncovers a Gene Module in Coronary Artery Disease Involving Transendothelial Migration of Leukocytes and LIM Domain Binding 2: The Stockholm Atherosclerosis Gene Expression (STAGE) Study

Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P<10−27and−30). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2–deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research

Prognostic value of CT coronary angiography in diabetic and non-diabetic subjects with suspected CAD: importance of presenting symptoms

AIM: To assess the prognostic relevance of 64-slice computed tomography coronary angiography (CT-CA) and symptoms in diabetics and non-diabetics referred for cardiac evaluation. METHODS: We followed 210 patients with diabetes type 2 (DM) and 203 non-diabetic patients referred for CT-CA for ruling out coronary artery disease (CAD). Patients were without known history of CAD and were divided into four categories on the basis of symptoms at presentation (none, atypical angina, typical angina and dyspnoea). Clinical end points were major cardiac events (MACE): cardiac-related death, non-fatal myocardial infarction, unstable angina and cardiac revascularizations. Cox proportional hazard models, with and without adjustment for risk factors and multiplicative interaction term (obstructive CAD 7 DM), were developed to predict outcome. RESULTS: DM patients with dyspnoea or who were asymptomatic showed a higher prevalence of obstructive CAD than non-diabetics (p\u2009 64\u20090.01). At mean follow-up of 20.4 months, DM patients had worse cardiac event-free survival in comparison with non-DM patients (90% vs. 81%, p\u2009=\u20090.02). In multivariate analysis, CT-CA evidence of obstructive CAD (in DM patients: HR: 6.4; 95% CI: 2.3-17.5; p\u2009100 in non-DM patients (HR: 5.6; 95% CI: 1.4-21.5; p\u2009=\u20090.01). In Cox regression analysis of the overall population, interaction term obstructive CAD 7 DM resulted in non-significance. CONCLUSIONS: Among DM patients, dyspnoea carried a high event risk with a MACE rate four times higher. CT-CA findings were strongly predictive of outcome and proved valuable for further risk stratification

Nanolayered siRNA delivery platforms for local silencing of CTGF reduce cutaneous scar contraction in third-degree burns

Wound healing is an incredibly complex biological process that often results in thickened collagen-enriched healed tissue called scar. Cutaneous scars lack many functional structures of the skin such as hair follicles, sweat glands, and papillae. The absence of these structures contributes to a number of the long-term morbidities of wound healing, including loss of function for tissues, increased risk of re-injury, and aesthetic complications. Scar formation is a pervasive factor in our daily lives; however, in the case of serious traumatic injury, scars can create long-lasting complications due to contraction and poor tissue remodeling. Within this report we target the expression of connective tissue growth factor (CTGF), a key mediator of TGFβ pro-fibrotic response in cutaneous wound healing, with controlled local delivery of RNA interference. Through this work we describe both a thorough in vitro analysis of nanolayer coated sutures for the controlled delivery of siRNA and its application to improve scar outcomes in a third-degree burn induced scar model in rats. We demonstrate that the knockdown of CTGF significantly altered the local expression of αSMA, TIMP1, and Col1a1, which are known to play roles in scar formation. The knockdown of CTGF within the healing burn wounds resulted in improved tissue remodeling, reduced scar contraction, and the regeneration of papillary structures within the healing tissue. This work adds support to a number of previous reports that indicate CTGF as a potential therapeutic target for fibrosis. Additionally, we believe that the controlled local delivery of siRNA from ultrathin polymer coatings described within this work is a promising approach in RNA interference that could be applied in developing improved cancer therapies, regenerative medicine, and fundamental scientific research