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Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) may have a direct effect on the development of atherosclerosis. However, the association of serum PCSK9 levels with calcification of the cardiovascular system, including the coronary vessels and cardiac valves, has not been fully elucidated. Methods: Serum levels of PCSK9 were measured in 470 patients (265 males; mean age, 68.4 ± 10.1 years) without previous aortic valve surgery who underwent coronary computed tomography angiography (CCTA). We evaluated the presence or absence of coronary artery calcification and aortic valve calcification. Results: Coronary artery calcification and aortic valve calcification were identified in 371 (78.9%) patients and 222 (47.2%) patients by CCTA, respectively. Patients with coronary artery calcification had a higher prevalence of aortic valve calcification than those without (54.7% vs. 19.2%, P<0.001). Serum levels of PCSK9 were significantly higher in women (276 ng/mL, interquartile range [IR] 214-330) than in men (236 ng/mL, IR 189-304, P<0.001). In age- and gender-adjusted logistic regression analysis, the highest quartile of PCSK9 (≥322 ng/mL) was significantly associated with coronary artery calcification (odds ratio [OR] 2.47, 95% confidence interval [CI] 1.31-4.67, P=0.005), but not with aortic valve calcification (OR 1.09, 95% CI 0.69-1.75, P=0.705). When age, gender, body mass index, smoking, estimated glomerular filtration rate (eGFR), hypertension, dyslipidemia, diabetes, and aortic valve calcification were used as covariates, the highest PCSK9 quartile remained independently associated with coronary artery calcification (OR 2.14, 95% CI 1.09-4.20, P=0.027). Conclusions: Serum PCSK9 level had an association with coronary artery calcification, but not with aortic valve calcification, independent of atherosclerotic risk factors and valvular calcification. PCSK9 may contribute to the development of coronary calcification. [ABSTRACT FROM AUTHOR]

Introduction: Guidelines recommend using pretest probability risk assessment to direct the diagnostic approach for coronary artery disease (CAD), but the best model for routine clinical use is unclear and national organizations provide different recommendations on which model to use. We sought to externally validate prediction models for obstructive CAD in a contemporary, real world population. Methods: Between June 2014 and June 2016, 727 symptomatic subjects (age 40-90 years without known CAD) referred for CAD evaluation underwent calcium scoring and coronary computed tomography angiography (CCTA). Obstructive CAD was defined as ≥50% stenosis on CCTA. Pretest probabilities for obstructive CAD were calculated using published coefficients for modified Diamond-Forrester (DF; age, sex, angina characteristic), CAD Consortium Basic (age, sex, angina characteristic), Clinical (Basic + diabetes, hypertension, dyslipidemia, smoking), and Extended (Clinical + coronary artery calcium score) models. Models were evaluated using C-statistics, calibration plots, and reclassification. Results: Median (5-95th percentile) age was 59.0 (44.9-76.0) years with 54% males. C-statistics were modified DF 0.677 (95% confidence interval: 0.617-0.734), CAD Basic 0.692 (0.632-0.747), Clinical 0.723 (0.669-0.774), and Extended 0.851 (0.813-0.886). Calibration was similar for the Clinical and Extended models. The Extended model classified the most subjects as low risk (390 with 9 having obstructive CAD) followed by Clinical (305 with 15 having obstructive CAD) and Basic (287 with 17 having obstructive CAD). The Extended model had comparable sensitivity and higher specificity (91% and 60%, respectively) to the Clinical (85% and 46%), Basic (82% and 43%), and modified DF (98% and 5%) models. Conclusions: The CAD Consortium Extended model incorporating coronary artery calcium score demonstrated improved discrimination and specificity for obstructive CAD, with comparable calibration and sensitivity. As compared to the Basic and Clinical models, the Extended model also classified the largest percentage of individuals as low risk, potentially sparing similar patients from further noninvasive and invasive testing. [ABSTRACT FROM AUTHOR]

Introduction: Atherosclerosis is a chronic inflammatory disease in the arterial wall. The ratio of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) to total fatty acids (FA), termed omega-3 FA index, predicts cardiovascular outcomes. EPA and DHA are precursors of specialized pro-resolving lipid mediators (SPMs) - resolvins (Rv) and maresins (MaR) - which resolve chronic inflammation. Objective: To examine the relationship between levels of EPA, DHA, SPMs and proinflammatory lipid mediators (LM) and coronary plaque progression. Methods: A total of 240 subjects with CAD on statins were randomized to 3.36 g of EPA and DHA daily or control for 30 months. Coronary plaque volume was measured by coronary computed tomographic angiography. Levels of SPMs and LMs - leukotriene B4(LTB4) and prostaglandin E2and D2- were measured with liquid chromatography-tandem mass spectrometry in the top and bottom 6% of subjects stratified by omega-3 FA index. Results: Levels of two SPMs, RvE1 and MaR1, were significantly higher in those with a high omega-3 FA index (median 8.4%) compared to a low index (median 2.4%). Those with a low omega-3 FA index had a low ratio of MaR1/LTB4and significant progression of all plaque subtypes (Table). Those with a high omega-3 FA index fell into two groups based on regression or progression of coronary plaque. Those with a high omega-3 FA index and low MaR1/LTB4ratio (median, 0.2 [IQR, 0.1 - 0.4]) had significant progression of fatty, fibrous, noncalcified and total plaque whereas those with a high omega-3 index and high MaR1/LTB4ratio (median, 2.3 [IQR, 0.5 - 2.7]) had significant regression of fatty, fibrous and noncalcified plaque. The MaR1/LTB4ratio was the strongest predictor of plaque change (r= -0.606, p = 0.001). Conclusions: A deficiency of SPMs and low ratio of MaR1/LTB4predict coronary plaque progression and suggest that an imbalance of proinflammatory to pro-resolving lipid mediators contributes to progression of coronary plaque. [ABSTRACT FROM AUTHOR]

Introduction: Aerobic exercise capacity measured in metabolic equivalents of task (METs) and amount of exercise are inversely related with cardiovascular (CV) morbidity and mortality and all-cause mortality in men and women. However, recent reports suggest that higher exercise volume may accelerate coronary plaque formation. In a study in athletes using self-reported exercise data converted to METs, athletes in the > 2000 Met-min/week group had a significantly higher prevalence of noncalcified plaque and coronary artery calcium (CAC), a measure of subclinical CV disease. In the CARDIA study, CAC was 1.86-fold higher in white males achieving ≥450 min of exercise/week (3x the recommended guideline of 150 min/week) over 25 years. Higher CAC scores predict higher CV events and mortality. Hypothesis: Higher exercise capacity (METs) is inversely associated with coronary plaque volume at moderate exercise volume. Methods: A total of 270 subjects with stable CAD underwent maximal exercise treadmill testing with calculation of METs. Noncalcified coronary plaque volume and CAC were measured with CT scanning. METs were divided into three groups and the association with plaque volume examined after multivariate adjustment. Results: Higher METs (≥ 10.6) with an average of 150 min/week of exercise were associated with a significantly larger volume of fibrous and total plaque but a lower CAC score after multivariate adjustment. After adjustment, no difference was observed in volume of fatty plaque, the plaque type more likely to rupture and cause an acute coronary syndrome. Conclusion: Higher exercise capacity in CAD subjects was associated with significantly more fibrous and total plaque but a lower CAC score after adjustment in subjects averaging 150 min exercise/week, the current guideline. Since higher CAC predicts CV events, our findings support a benefit of the current physical activity guideline of 150 min/week as opposed to higher amounts of exercise. [ABSTRACT FROM AUTHOR]

Background: Coronary Artery disease is the leading cause of death. Its workup is performed annually in > 20 million patients worldwide. Several patients are misdiagnosed with non-cardiac chest pains and eventually die from a cardiovascular event in the subsequent follow-up within five years. We performed this meta-analysis to compare the efficacy of Coronary Computed Tomography Angiography (CCTA) to non-invasive testing (NIT) with and without imaging in the workup of acute and stable chest pain. Methods and Results: We searched PubMed and Medline from from January 01, 2007 until January 01, 2018, for Randomized Control Trials (RCTs) comparing CCTA to NIT in patients who presented with acute or stable chest pain. We included sixteen RCTs enrolling 21,199 patients. We used RevMan Version 5.3 Copenhagen for review and analysis. CCTA was associated with significant reduction in Myocardial Infarctions (MI), 115vs.156, Risk Ratio (RR)=0.71, 95% Confidence Interval (CI)=0.56-0.91, p<0.006, I2=0%, with no difference in mortality, RR=.93, CI=0.71-1.21, p=58, I2=0%. This difference was driven by the decreased incidence of MIs in the stable chest pain subgroup, 80vs.120, RR=0.66, CI=0.50-0.88, p=0.004, I2=0%, as compared to acute chest pain subgroup, where there was no statistical difference in the incidence of MI in either arm, 35vs.36, RR=0.88, CI=0.54-1.44, p=0.54, I2=0%. There were significantly more true positive invasive coronary angiograms (ICA) and revascularization with significantly reduced follow-up testing and recurrent hospital visits after CCTA. There was significantly higher exposure to radiation with an increasing trend of unstable anginas after CCTA. Conclusions: This analysis demonstrates a significantly reduced MIs, recurrent hospital visits and downstream follow-up testing after CCTA with no difference in mortality. [ABSTRACT FROM AUTHOR]

Introduction: Racial differences in the prevalence of coronary artery calcification (CAC) are well documented. African Americans (AA) tend to have a lower prevalence of CAC despite greater coronary risk factors and according to some reports higher cardiovascular disease (CVD) morbidity and mortality Hypothesis: We hypothesize despite a lower prevalence of CAC; AA would have similar or higher burden of non-calcified plaque (NCP). Methods: We retrospectively evaluated data from 4280 (3886 whites and 482 AA) consecutive patients, who underwent non-contrast and contrast cardiac computed tomography at our center. We used the 17-segment American Heart Association classification for assessment of coronary arteries. We quantified the amount of plaque in each segment as mild (score of 1), moderate (score of 2), or severe (score of 3) using a previously described method. We calculated total plaque score (TPS) by summation of the amount of plaque of each coronary segment. The non-calcified plaque score (NCPS) and mixed plaque score (MPS) were similarly calculated by summing the plaque scores in each segment separately. The segment involvement score (SIS), ranging from 0 to 17, was calculated as the total number of segments with any plaque; the segment stenosis score (SSS), was obtained by grading the stenosis severity of each segment with plaque, as was previously described in literature. Results: Prevalence of CAC>0 was 77% in whites versus 61% in AA (median Interquartile range]:190[13-780] versus 38[0-275];P<0.001). After adjustment for age, diabetes, BMI, family history of CAD, chest pain, hyperlipidemia, HTN and smoking, there was no significant difference in NCPS (β(Se) = 0.1 (0.4), P=0.731) and MPS (β(Se) = -0.4 (0.8), p=0.590) in AA compared with whites. TPS (β(Se) = -1.6 (0.4), P<0.001), SSS (B(Se)=-1.5(0.5), p<0.001 and Segment involvement score (B(Se)= 0.9 (0.2), P<0.001) were significantly lower in AA compared with whites. Conclusion: Despite the significantly lower prevalence of CAC in AA, the burden of NCP and mixed plaque were similar in AA compared with whites. Further studies would be needed to elucidate whether the higher burden of NCP burden despite a lower prevalence of CAC is responsible for higher CVD mortality in AA. [ABSTRACT FROM AUTHOR]

Introduction: Flow-mediated vasodilatation rate (FMD) is an ultrasound measurement often used to assess vascular endothelial function. Endothelial dysfunction causes coronary atherosclerosis by decreasing nitric oxide levels, which alters vasodilation and causes destabilization of established plaque. Hence, FMD has been proposed to be a surrogate marker of atherosclerosis severity and predictive of cardiovascular outcomes. Hypothesis: We intend to evaluate the relationship between the severity of Coronary Artery Disease (CAD) and FMD. We hypothesize that patients with lower FMD would have more severe CAD when compared to individuals with higher FMD. Methods: We identified 291 patients (169 [58%] male, mean age 59.6 ± 11.3 years), clinically referred for Coronary Artery Calcium(CAC) Scoring and Coronary Computed Tomography Angiography (CCTA) at our center. After informed consent, we measured brachial artery FMD using ultrasound (UNEXEF, Unex, Japan). CAC was measured using Agatston method. Segment Involvement Score (SIS; the total number of segments with any plaque), Segment Stenosis Score (SSS; the sum of maximal stenosis score per segment), Total Plaque Score (TPS; the sum of all segments plaque burden) were assessed using the 17-segment model with CCTA. We calculated the median FMD. We used multivariate regression analysis to analyze the association between FMD and the markers of CAD (i.e., CAC, TPS, SSS, SIS), after adjusting for confounding variables. Results: Median FMD in the group was 4.1% (25%-75%: 2.2-6.0). After multivariable analysis, individuals with FMD lower than 4.1% were noted to have significantly higher CAC (p=0.024), TPS (0.024), SSS (p=0.015) and SIS (p=0.010). (Table 1) Conclusions: We conclude that impaired FMD rate is an indicator of more severe coronary artery disease. Further studies to evaluate non-invasive ultrasound FMD measurement as a tool for predicting subclinical atherosclerosis and mechanisms are warranted. This could also serve to provide additive information for risk stratification of patients and cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

A 38-year-old athletic man with a history of exercise-induced anaphylaxis and syncope presented to clinic with three sporadic episodes of exertional chest discomfort and an abnormal electrocardiogram. After evaluation, the dominant suspicion was for a syndrome with coronary involvement—chief among these being a congenital anomalous coronary artery. A coronary CT angiogram revealed no atherosclerosis and was without coronary anomaly. Instead, a 5.0 cm x 4.7 x 4.8 arterially enhancing intrapericardal mass with innumerable collaterals parasitizing the right and left coronary supply was visualized (See Image). A differential diagnosis for the mass included sarcoma, lymphoma, pericardial Castleman's Disease, angiosarcoma, hemangioma, and paraganglioma. Due to several radiographic and clinical features, a cardiac paraganglioma was favored. Coronary angiography revealed a preaortic bicoronary tumor blush with innumerable collaterals arising from the right coronary artery and a dominant arterial collateral arising from the first diagonal artery. Urine and serum metanephrine testing was negative. Given our high index of suspicion, selective testing for plasma and urinary dopamine revealed significantly elevated levels (42 fold the upper limit of normal) and biochemically confirmed an exclusively dopamine-secreting cardiac paraganglioma. In contrast to intradrenal pheochromocytoma, paraganglioma are extraadrenal neuroendocrine tumors arising from autonomic paraganglia and may secrete catecholamine. Cardiac paraganglioma are extremely rare tumors. Complete surgical resection offers curative potential however given their location, hypervascularity, and locally invasive nature, complex surgical methods are often required (including autotransplantation) to achieve clear margins. This case features a rare cause of chest pain and highlights the role of multidisciplinary involvement as well as multimodality investigation. [ABSTRACT FROM AUTHOR]

Introduction: Studies have shown that South Asians (SA) (individuals from India, Pakistan, Bangladesh, Nepal, and Sri Lanka) living in the United States (U.S.) have a high rate of Cardiovascular Disease (CVD). Traditional risk factors have not adequately explained this. We aimed to investigate if differences in coronary plaque prevalence and composition could explain the higher rates of CVD seen in SA. Methods: We identified 4,135 Caucasian or SA patients clinically referred to undergo Coronary Artery Calcium (CAC) scoring and Coronary Computed Tomography Angiography (CCTA) at our center. 249 self-identified themselves as SA, and 3,886 as Caucasians. 188 of the SA and 2,755 of the Caucasians were male. The average age among SA was 60.4 + 12.5 years, and Caucasians was 63 + 11.6 years (p<0.0001). The average Body Mass Index (BMI) was 26.5 + 3.9 among South Asians & 27.8 + 5.5 among Caucasians (p<0.0001). CAC was scored using Agatston method. Plaque Severity Score (PSS) (minimal-1; mild-2; moderate-3; severe-4) for non-calcified and mixed plaques were calculated separately for the 17-segment American Heart Association model. Total Plaque Severity Scores (TPS) were obtained by adding the corresponding PSS for these two types of plaque. Multivariate regression analysis was used to analyze differences in calcified, non-calcified & mixed plaque burden between the groups. Results: After multivariable analysis, when compared to Caucasians, South Asians had significantly higher mixed plaque (ß 4.9, SE 1.0, CI 2.9- 6.9, p <0.001). No statistically significant difference was noted in non-calcified plaque and CAC burden (Table 1). There was no difference in prevalence of disease between the races either. Conclusions: Our results add to the concept of ethnic differences in plaque composition, which accounts for higher subclinical atherosclerosis in South Asians and hence, higher rates of CVD. Further studies to investigate plaque progression, vulnerability characteristics and their effect on prognosis among ethnic groups are warranted. [ABSTRACT FROM AUTHOR]

Introduction: By indirectly measuring adipocyte lipid content, pericoronary adipose tissue (PCAT) CT attenuation measured from CTA may be a new promising metric to identify coronary inflammation. Hypothesis: We hypothesized PCAT CT attenuation may be related to changes in coronary plaque composition and progression. Methods: We analyzed CTA data sets of stable patients with CAD (N=111, age 59.2±9.8 years, male 76%) who underwent sequential CTA with the same acquisition protocol (3.4±1.6 years apart). The volumes and burden (plaque volumex100%/vessel volume) of total (TP), calcified (CP), non-calcified (NCP) and low-density non-calcified (LD-NCP, NCP < 30 Hounsfield Units (HU)) plaque were quantified using semi-automated software. PCAT CT attenuation (HU) was measured in 3D layers around the proximal segment of the right coronary artery (RCA) (Figure 1 a-f). Results: Age, gender and risk factors were similar between patients with an increase of NCP burden compared to patients with a decrease of NCP burden (each p>0.05). Patients with an increase of NCP burden showed an increase of PCAT CT attenuation, whereas patients with a decrease of NCP burden showed a decrease of PCAT CT attenuation (4.4 HU vs. -2.78 HU, p<0.0001). Patients with an increase of NCP burden showed a higher baseline PCAT CT attenuation compared to patients with a decrease in NCP burden (-73.1 HU vs. -76.1 HU, p=0.03). In multivariable analysis, only baseline PCAT CT attenuation (Odds Ratio (OR) 1.32, 95%CI: 1.03-1.68; p=0.029) and its change (OR 2.39, 95%CI: 1.6-3.5; p<0.001) were independently related to an increase in NCP burden, as well as in TP burden. Changes in PCAT CT attenuation showed correlation with changes in the burden of NCP (r=0.513, p<0.001) and LD-NCP (r=0.247, p=0.009); but not CP burden (p>0.05). Patients with statin therapy started after baseline CTA showed a trend towards reduction of PCAT CT attenuation compared to patients without statins (-1.61 HU vs. 1.39 HU, p=0.065). Conclusions: PCAT CT attenuation may potentially help to identify coronary arteries at increased risk of plaque progression derived from routine CTA. [ABSTRACT FROM AUTHOR]

Background: HIV-infected (HIV+) individuals are at increased risk of cardiovascular disease (CVD). CVD risk scores are commonly used to identify patients at high risk for optimal long-term prevention strategies. We evaluated the association of ACC/AHA pooled cohort equation (PCE) risk categories and coronary artery plaque volume progression by HIV serostatus in the Multicenter AIDS Cohort Study (MACS). We also evaluated whether Data collection on adverse events of anti-HIV drugs (D:A:D) risk categories more precisely identified plaque progression in HIV+ men. Methods: We studied men with and without HIV infection enrolled in the MACS CVD study. Cardiac computed tomography angiography was performed to assess coronary artery plaque volume at baseline and follow-up (median 4.6 yrs). Plaque progression was stratified into tertiles. We examined the association between baseline CVD risk score categories among men with a plaque at baseline with coronary artery plaque volume progression by multinomial logistic regression, stratified by HIV serostatus and adjusted for HCV, scanning site, and statin use. Results: We studied 363 men (154 HIV-, 209 HIV+) with median age 53 yrs for HIV- and 49 yrs for HIV+ men. ACC/AHA categorized 97 (63%) HIV- men and 106 (51%) HIV+ men in the high-risk PCE category. The odds of total plaque volume (TPV) and non-calcified plaque volume (NCPV) progression in the highest relative to lowest tertile was 4.8 (95% CI 1.9- 11.8, p<0.001) and 5.2 (2.0-13.4, p<0.001) times greater, respectively, among HIV- men in the PCE high-risk vs. moderate/low-risk category. Among HIV+ men, no association was found for TPV and NCPV progression by PCE categories in high risk vs. moderate/low risk, OR 1.0 (0.5, 2.1) and OR 1.5 (0.7, 3.1) respectively (p-values for interaction by HIV=0.02 and 0.08). Similarly, the D:A:D high-risk category was not associated with the highest tertile of plaque progression among HIV+ men (OR 1.1 (0.5,2.4). Conclusions: PCE categories predict plaque progression better among HIV- men compared to HIV+ men. Improved CVD risk scores are needed to identify high-risk HIV+ men for more aggressive CVD risk prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Conventional risk stratification for suspected coronary artery disease (CAD) results in a low proportion of positive findings in patients referred to non-invasive tests. The novel stethoscopic device (CADscor©), uses advanced analysis of sounds from the coronary circulation and myocardium in combination with age, gender and blood pressure to detect CAD. In the current database study, recordings of heart sounds were processed using the CAD-score algorithm to validate the rule-out potential of a re-classification scheme combining the CAD-score and the Diamond-Forrester score. Methods: The database included audio recordings from 2373 patients (female: 53%, mean age 58.3±8.4 years) from three studies: the Dan-NICAD study in symptomatic patients referred for coronary CTA (n= 1525), a cohort of asymptomatic subjects undergoing calcium scoring in the Dan-Risk study (n= 622) and a study including symptomatic patients referred for either coronary CTA or coronary angiography (CAG) (n= 226). Patients whose CTA or calcium score indicated CAD were referred to CAG. CAD was defined as ≥50% diameter stenosis confirmed by CAG. Pre-test risk was calculated using the updated Diamond-Forrester and patients were classified according to the current ESC guideline for stable angina: low risk <15%, intermediate risk 15-85% and high risk >85%. Patients in the intermediate risk group were re-classified to low risk if the CAD-score was below or equal to 20 out of 100. Results: The CAD-score could be calculated in 2237 (94.3%) of the audio recordings, of these 212 (9.5%) patients tested positive for obstructive CAD. The CAD-score was significantly higher in confirmed CAD patients 38.4 (SD: 13.9) versus 25.1 (SD: 13.8) in remaining patients (p<0.001). A total of 863 (38.6%) patients had a CAD-score at or below 20. Using the proposed reclassification scheme the number of patients in the low risk group increased from 369 (16.5%) to 977 (43.7%) thus reducing the number of patients classified as intermediate risk from 1817 (81.2%) to 1209 (54.5%). Before reclassification 7 (1.9%) patients classified as low-risk patients tested positive for CAD, whereas post-reclassification this number was increased to 28 (2.9%) (p=0.32). Net reclassification index was 0.19. Conclusion: In the current database study the re-classification scheme, based on a new acoustic score, reduces the number of patients in the intermediate risk group, which are candidates for non-invasive testing, without significantly increasing the disease prevalence in the low risk group. [ABSTRACT FROM AUTHOR]

Introduction: Aortic Root and valve replacement using freestyle porcine stentless bioprosthesis provides superior geometry and hemodynamics, which could translate into low thrombogeneicity, obviating the need for anticoagulation. To date there has been no systematic studies of leaflet thrombosis. Methods: 173 patients underwent aortic root replacement with a Freestyle root in a single center from 2009 to 2017. 70 patients were screened for leaflet thrombosis using MSCT. Leaflet thrombosis was defined as reduced leaflet motion by 50% on time-resolved 4D MSCT associated with hypoattenuating leaflet thickening. Data on anticoagulation and clinical outcomes were collected. Results: 70 patients were examined with mean age of 35±5 years. 12 patients (17%) were on anticoagulation either for AF or for other valve replacement. Leaflet thrombosis was found in 15 patients (21%). The cumulative probability of leaflet thrombosis was 4±2% at 2 years, 14±4% at 3 years and increased to 35±8% at 5 years. There was a trend towards an association between an implanted Freestyle size>25 mm and the hazard of leaflet thrombosis (P=0.059). Thrombus occurred usually on NCC (73%), and less frequently on LCC (27%), 2 patients had thrombus on both NCC and LCC. (Figure 1) No thrombus occurred on RCC. No patient had stroke or thromboembolic events, and the mean gradient across the valve was 10±3 mmHg with no significant incompetence. Conclusion: This study has documented the occurrence of subclinical leaflet thrombosis in patients with Freestyle aortic root replacement. This can develop both early and late after replacement. The influence of these findings on long term valve function, stroke and response to the anticoagulation needs urgent investigations. Figure 1: showed hypoattenuating opacities on 2D MSCT (maximum intensity projection of gray-scale image) and volume-rendered MSCT (color images) of freestyle valves during diastole and systole. The hypoattenuating lesions always involve the leaflet base and extend to the center of the frame. Leaflets with reduced motion are visible as wedge-shaped or semilunar opacities in both systole and diastole. (A) thrombus was in NCC. (B) thrombus was in LCC. [ABSTRACT FROM AUTHOR]

Introduction: Plasma sphingolipids, particularly ceramides, have emerged as one of several non-cholesterol lipids that predict cardiovascular outcomes. In the early phase of acute myocardial infarction (MI), plasma LDL-C concentrations fluctuate and hence may not be reliable prognostic biomarkers. Hypothesis: We hypothesized that specific sphingolipid species correlate with plasma LDL-C and that such associations may identify sphingolipid species with prognostic potential. Methods: Using targeted mass spectrometry, we profiled 75 plasma sphingolipid species in 652 patients within 48 hours of MI to determine their association with plasma LDL-C concentrations and 12-month major adverse cardiovascular and cerebrovascular events (MACCE). Results: The median age was 60 years and 18.6% were women. 15 sphingolipid species, including ceramides, were positively correlated with LDL-C, HDL-C and TG but only the lactosylceramide (LacCer) and glucosylceramide (GluCer) species, were uniquely correlated with LDL-C (correlation coefficient 0.23 for LDL-C, 0.02 for TG and 0.05 for HDL-C). During the follow-up period of 371 days, 51 cardiovascular events occurred. After multivariable adjustment with the GRACE score, LDL-C concentration was not associated with MACCE, HR 0.94 (0.67 - 1.31) for each SD increase. The ratios of Cer (d18:1/16:0)/Cer (d18:1/24:0), Cer (d18:1/18:0)/Cer (d18:1/24:0) and Cer (d18:1/24:1)/Cer (d18:1/24:0) were all associated with MACCE, as were LacCer (d18:1/18:0)/Cer(d18:1/24:0), LacCer (d18:1/20:0)/Cer(d18:1/24:0), LacCer(d18:1/22:0)/Cer(d18:1/24:0) and LacCer (d18:1/24:0)/Cer(d18:1/24:0), but not GluCer/Cer ratios. Among STEMI patients, only 2 of the non-glycosylated ceramide ratios were associated with MACCE, while five LacCer species were associated with MACCE (LacCer(d18:1/16:0)/Cer(d18:1/24:0), LacCer(d18:1/18:0)/Cer(d18:1/24:0), LacCer (d18:1/20:0)/Cer(d18:1/24:0), LacCer (d18:1/22:0)/Cer(d18:1/24:0) and LacCer(d18:1/24:0)/Cer(d18:1/24:0). Conclusion: In early phase of acute MI, LDL-C does not predict future cardiovascular outcomes. LacCer is uniquely correlated with LDL-C and LacCer/Cer ratios appear to be powerful prognostic biomarkers, especially in the STEMI population. [ABSTRACT FROM AUTHOR]

Introduction: Assessment of regional cardiac function is important in the diagnosis and treatment of cardiac diseases such as myocardial ischemia, heart failure, and dyssynchrony. We present a method to leverage the high fidelity of x-ray CT to quantify regional LV function using temporal changes in the topography of the trabecular tissue across the cardiac cycle. Methods: Cine CT images of 14 subjects were acquired with standard clinical protocols. Based on a radiologist's clinical impression, ejection fraction, visual assessment of wall motion, and radial strain, 8 subjects were categorized as normal and 6 as abnormal. All abnormal subjects exhibited dysfunction in the mid-anterior and the mid-inferolateral segments. Regional topography characterization was measured by calculating the fractal dimension (FD) of the endocardium, from the segmented blood pool. The average FD within each of the 16 AHA segments was calculated for 20 time frames of the cardiac cycle. Normal from abnormal function was differentiated through principal component analysis of changes of FD over time (ΔFD). Results: Normal and abnormal subjects showed significantly different ΔFD values in the mid-anterior (0.14 ± 0.04 vs 0.04 ± 0.01, p < 0.0001) and the mid-inferolateral (0.15 ± 0.04 vs 0.05 ± 0.01, p < 0.0001) segments, reflecting differences in the changes in topography of the trabecular tissue during systole between the two cohorts. The principal component analysis of the time-varying FD revealed a distinction between normal and abnormal function. Conclusion: We developed a method to evaluate regional LV function from clinical cine CT images using the change in fractal dimension of the endocardial surface. The results from the study agreed with wall motion abnormalities seen on the cine CT images and with radial strain measurements. [ABSTRACT FROM AUTHOR]

Introduction: Patients with family history of premature coronary artery disease (CAD) are at risk of CAD events at younger age. Risk factor based approaches and clinical evaluation are the commonly used methods of assessment. Recently it was shown up to 50% of individual presenting with their first myocardial infarction (MI) were considered "low risk" prior to that event. MI is often a result of plaque rupture preceded by progression of subclinical atherosclerosis. Therefore, detection of subclinical atherosclerosis may help target prevention of plaque progression. In this study, we assessed the predictive value of clinical risk factor, biomarkers and Framingham Risk Score (FRS) in predicting subclinical atherosclerosis in this population. Methods: From 230 referrals,182 individuals with a family history of premature CAD, Patients between the ages of 35 to 55 were enrolled in the Early Atherosclerosis Clinic at St. Paul's Hospital, Vancouver, Canada for evaluation of risk of CAD. Premature CAD was defined as CAD events in first-degree family members (male< 55, female< 65). Patients underwent clinical and risk factor evaluations as well as Cardiac CT or Calcium Score (CS) to assess presence of subclinical/clinical atherosclerosis if indicated by the treating physician. Results: In this pilot, 67 individuals (55% male, mean age 45.8 ± 6.0 years) completed evaluation, 31(46%) had evidence of subclinical atherosclerosis on CT coronary angiography or CT calcium score with a mean segment involvement score (SIS) of 3.1 and mean CS of 128. Aside from male sex and age, other risk factors and biomarkers including diabetes mellitus, hypertension, smoking history, total cholesterol, LDL-C, HDL-C, Cholesterol/HDL-C ratio and FRS were not significantly different between those with or without subclinical atherosclerosis (Table 1). Conclusions: In young individuals with a family history of premature CAD, risk factors, biomarkers, and FRS failed to identify patients with premature, subclinical atherosclerosis in this pilot study. Detection of subclinical atherosclerosis and early implementation of treatment with the aim of stabilizing plaques and stopping progression might prove vital in reducing events in these individuals. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Atrial fibrillation is associated with increased risk of thrombus formation, especially in the left atrial appendage (LAA). This is thought to occur at least in part be due to abnormal left atrial (LA) hemodynamics associated with the loss of sinus rhythm. However, there is a lack of personalized quantitative tools to guide decisions regarding anticoagulation treatment. The goal of this work is to quantify blood stasis in the LA to determine how LAA morphology, contractility, and hemodynamics influence thrombosis risk. Methods: We developed a 3-D computational fluid dynamics (CFD) model of LA hemodynamics, with moving boundaries obtained from time-resolved CT scans. Blood stasis was evaluated from the computed blood velocity by calculating blood residence time (RT). We present data from simulations of N=5 patient-specific anatomies, including one case with atrial fibrillation and one case with a LAA thrombus (digitally removed). For each subject, we performed simulations with moving LA walls and simulations with fixed walls. Results: In all subjects, blood residence time was highest inside the LAA (Figure 1), consistent with evidence that thrombus formation preferentially occurs in the appendage. The averaged residence times inside the LAA showed a moderate correlation with the inverse of LAA ejection fractions across different subjects (R = - 0.8, p = 0.2). However, the residence time for each patient varied little between the moving-wall and the fixed-wall simulations (Mann-Whitney p = 0.9). On the other hand, LAA RT showed a strong inverse correlation with the ratio VTI/LLAA, where VTI is the velocity time integral of blood velocity at the LAA orifice and LLAAis the left atrial appendage length (R=0.95, p=<0.01). This ratio reflects the fraction of the blood pool along the LAA length that is completely washed out each cardiac cycle. Conclusions: We developed a 3-D patient-specific computational fluid dynamics framework to map blood flow in the left atrium. Our results show that left atrial appendage anatomy and flow are important factors that affect blood stasis more than wall motion. This high-fidelity framework allows us to derive and validate simplified indices of blood stasis that can be measured by standard cardiac imaging modalities. [ABSTRACT FROM AUTHOR]

Introduction: The basis of discordance between invasive coronary angiographic (ICA) anatomical stenosis and physiological fractional flow reserve (FFR) remains poorly understood. Hypothesis: We assumed the plaque characteristics have more powerful influence on FFR rather than lesion territory myocardial mass in nonobstructive left anterior descending artery (LAD) lesions. Methods: Coronary CT angiography (cCTA), ICA and FFR underwent within 4 weeks in 104 patients. cCTA-verified plaque characteristics (Area remodeling index (ARI), low attenuation plaque (LAP≤30HU), %Plaque Area (%PA), Vessel Area (VA) at minimum lumen area (MLA)) and lesion territory myocardial absolute mass (Mass) and %mass of LV mass (%Mass) between 51 consecutive ICA-FFR mismatches (ICA-quantitative coronary angiography (QCA) <50%, FFR ≤0.8) and 53 ICA-FFR matches (ICA-QCA <50%, FFR >0.8) were compared. Results and Conclusions: cCTA-verified VA (20.5±0.06 vs. 16.7±0.05 mm2, P=0.0008), ARI (1.38±0.24 vs. 1.05±0.11, P<0.0001), %PA (64.5±12.9 vs. 57.0±8.4 %, P=0.0006), the prevalence of LAP (81.3 vs. 18.1 %, P<0.0001) at MLA, Mass (46.2±18.5 vs. 37.1±14.3 cm3, P=0.0056) and %Mass (35.2±10.4 vs. 30.2±9.4 %, P=0.012) were significantly higher in the ICA-FFR mismatch than the match group. ARI (Odds Ratio 56.6, 95%CI: 9.56-335.75, P<0.0001), %plaque area (OR 56.6, 95%CI: 9.56-335.75, P<0.0001) and presence of LAP (OR 5.84, 95%CI: 1.39-24.60, P=0.016) were independent significant predictors of ICA-FFR mismatch in multivariable logistic regression analysis. Mass (OR 8.91, 95%CI: 0.876-90.66, P=0.065) and %Mass (OR 4.25, 95%CI: 0.981-18.390, P=0.0531) are not significant independent predictors. By receiver operation curve analysis, the areas under the curve for ARI and %PA were 0.921 and 0.682 respectively for the diagnosis of mismatch (best cut off values 1.13 and 65.6% respectively. The sensitivity and specificity ARI >1.13 for predicting ICA-FFR mismatch were 90.2% and 79.2%, respectively. In conclusion, CTA-derived ARI, %PA and LAP have more powerful influence on FFR rather than Mass or %Mass in the absence of anatomically significant stenosis in LAD. [ABSTRACT FROM AUTHOR]

Introduction: Single photon emission computed tomography myocardial perfusion (SPECT-MPI) is increasingly being acquired with non-contrast CT for attenuation correction, which allows coronary artery calcium (CAC) scoring. We investigated the value of CAC scanning for identifying patients with obstructive coronary artery disease (CAD) in the absence of myocardial perfusion abnormalities. Methods: From the CORE320 multicenter study, we studied 188 patients with suspected CAD who were referred for invasive coronary angiography (ICA) and had normal SPECT-MPI. Cardiac CT and SPECT-MPI were obtained separately. Patients were stratified based on pretest probability and history of CAD into two groups: low/intermediate risk (N=96) and high risk/history of CAD (N=92). The area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic accuracy of CAC scoring for identifying patients with obstructive CAD defined as at least one ≥50% stenosis by quantitative ICA. Other endpoints were: multi-vessel CAD (≥2 vessels with ≥50% stenosis) and high-risk anatomy (left main stenosis of ≥50%, 3-vessel CAD, or 2-vessel CAD with involvement of the proximal LAD artery). Results: The median age was 63 years and 59% were male. Despite the absence of perfusion abnormalities by SPECT-MPI, 28% in the low/intermediate risk group and 64% in high risk group had obstructive CAD. AUC (95% CI) of CAC scoring for detecting obstructive CAD was 81 (71-88) in the low/intermediate risk group and 72 (61-81) in the high risk group (Table). Six percent (2 of 34) in the low/intermediate risk group and 43% (3 of 7) in the high risk group had obstructive CAD despite absence of CAC. Conclusion: CAC scanning yields good accuracy for detecting obstructive CAD in symptomatic patients who have normal SPECT-MPI results. A CAC score >400 was strongly suggestive of high-risk coronary anatomy in our cohort. Routine integration of the CAC score with SPECT-MPI interpretation may be valuable. [ABSTRACT FROM AUTHOR]

Introduction: Patients with type 2 diabetes have a higher prevalence and extent of coronary atherosclerosis and higher rates of silent atherosclerotic lesion without ischemic symptoms. Therefore, the risk prediction and early screening for coronary artery disease (CAD) is important in this population. However, there is a controversy in performing routine screening for CAD due to low sensitivity and specificity. Purpose: The aim of study was to develop a clinical risk scoring system for risk stratification to predict the likelihood of obstructive CAD among asymptomatic type 2 diabetic patients. Methods: From January 2006 to December 2010, we prospectively enrolled 933 asymptomatic patients with type 2 diabetes and no prior CAD who underwent CCTA. Obstructive CAD was defined as ≥50% stenosis in any coronary artery segment on CCTA. We developed the clinical scoring system using traditional risk factors representing the presence of obstructive CAD by multivariate logistic analysis. Results: Obstructive CAD was detected in 374/933 (40.1%) patients. Among all baseline demographic, clinical, and laboratory variables, we found 7 factors (age ≥65 years, male gender, prior stroke, hypertension, diabetes duration ≥10 years, and HbA1c >7.0, abnormal ECG) that were independently associated with an elevated risk of obstructive CAD. According to the regression coefficients of each variable, the clinical scoring system was created, with scores ranging from 0 to 9 points. The C-statistic of the scoring system was 0.677. The prevalence of obstructive CAD according to the scoring system was 0: 7.7%, 1: 24.0%, 2: 24.3%, 3: 32.8%, 4: 42.8%, 5: 54.6%, 6: 58.3%, 7: 70.8%, 8: 78.6%, 9: 100%. (Figure 1.) Conclusion: The clinical scoring system accurately predicted the presence of obstructive CAD in asymptomatic diabetic patients. It may help to identify and counsel high-risk patients requiring CAD screening, also support physicians to make appropriate therapeutic decision. [ABSTRACT FROM AUTHOR]

Background: Cardiac magnetic resonance imaging has been shown to be beneficial for identification of the ventricular tachycardia (VT) substrate prior to catheter ablation. Contrast-enhanced multidetector CT (CE-MDCT) is more generalizable to clinical practice; and wall thickness on CE-MDCT can identify potential substrate sites albeit with decreased specificity. Objective: We sought to evaluate the association between endocardial hypoattenuated areas in CE-MDCT with local conduction velocity and electrogram abnormalities in patients with post-infarct VT. Methods: 14 patients (mean age 64.2 ± 13.3, 79% male) with post-infarct VT underwent pre-procedural CE-MDCT followed by endocardial electroanatomical mapping (EAM) and ablation. Endocardial attenuation and wall thickness were calculated from 3D MDCT images using ADAS-VT software (Galgo Medical, Spain). EAM was registered with 3D MDCT images using the CartoMERGE module of CARTO3 software (Biosense Webster Inc. Diamond, CA). Local conduction velocity was calculated by averaging the velocity between each point and 5 adjacent points with concordant wave-front direction. Results: Mean endocardial attenuation and local conduction velocity were 73.2 ± 42.7 HU and 0.54 ± 0.40 m/s, respectively. In multivariable regression analysis clustered by patient, local conduction velocity was positively associated with endocardial attenuation, bipolar voltage, unipolar voltage and wall thickness. Each 10 HU drop in endocardial attenuation correlated to 1.2% decrease in conduction velocity (p<0.001) and 2.8% decrease in bipolar voltage amplitude (p<0.001), after adjusting for wall thickness and epicardial attenuation. Conclusion: The endocardial attenuation distribution on CE-MDCT is associated with regional conduction velocity and electrogram amplitude. Regions with low conduction velocity identified with low attenuation on CE-MDCT may serve as important VT substrates in post-infarct patients. [ABSTRACT FROM AUTHOR]

Introduction: Atrial fibrillation is the most common clinical arrhythmia. Catheter ablation has become an increasingly safe and effective therapy in recent years. Cardiac Computerized Tomography (CT) is performed for pulmonary vein mapping, to exclude left atrial appendage thrombus and to identify left atrial anatomic variants. We aimed to identify the impact of pre-procedural cardiac computerized tomography (CT) on procedural efficacy, complications and clinical outcome in patients undergoing catheter ablation for atrial fibrillation (AF). Methods: In this retrospective review, 271 consecutive patients (Mean age 61 yrs, paroxysmal (73%) and persistent (23%) AF were analyzed. 58% underwent RF ablation, 24% Cryoablation and 18% both, respectively. Procedural and clinical outcomes were compared among patients who underwent catheter ablation with and without pre-procedural cardiac CT. Results: 153 patients had a pre-procedural cardiac CT and 118 patients did not undergo a pre-procedural CT scan. The mean duration of the procedure (280.4±80.7 vs 258.8±87.7, p=0.036) was higher in the CT group but fluoroscopy time (35.3±16.9 vs 46.6±26.7, p<0.0001) and procedural radiation exposure (968.5±854.7 vs 1233.9±980.0, p=0.006) was lower in CT group. The need for additional substrate ablation beyond PVI was similar in both CT and no CT group (59% vs 63% p=0.49). The occurrence of complications such as bleeding, pericardial tamponade, pneumothorax, infection and embolic events were similar in both groups. Amongst patients with available follow up, we noted a non-significant risk of AF recurrence at 3 (21.6% vs 20% p=0.7) and 12 months (33.3% vs 35% (p= 0.8) between the two groups (CT cohort vs No CT cohort). On logistic regression analysis, adjusting for higher baseline proportion of patients with persistent atrial fibrillation in the CT cohort (33% vs 19% p=0.012) as covariate, atrial fibrillation recurrence remained similar at 3 months (Odds ratio 1.2, 95% CI 0.6-2.5) and 12 months (Odds ratio 0.9, 95% CI 0.5-1.7 p=0.75) Conclusions: In AF patients , performing CT prior to catheter ablation does not appear to provide additional benefit in terms of need for additional substrate ablation beyond pulmonary vein isolation, AF recurrence at 3 months or 1 year. The procedural fluoroscopy time and radiation exposure, was significantly less in the group that had pre-procedure cardiac CT. [ABSTRACT FROM AUTHOR]

Introduction: Computed tomography-derived fractional flow reserve (FFR-CT) has recently been introduced in clinical settings as one of the novel coronary imaging technologies. However, the ideal position for FFR-CT measurements is unknown. Hypothesis: The ideal position for FFR-CT measurement should be at the mid-distal site, where the distal sensor of the invasive fractional flow reserve (FFR) wire is expected to be placed, as far-distal FFR-CT measurements may overestimate the presence of ischemia. Methods: The FFR-CT and invasive FFR values were assessed prospectively in 390 vessels (luminal stenosis in coronary CT ≥ 50%) in 267 patients at our institution. FFR-CT was measured at far-distal and mid-distal (Figure), where the distal sensor of the invasive FFR wire is expected to be placed. The predictive accuracies of mid- and far-distal FFR-CT were compared using the DeLong method of area under the curve (AUC) of the receiver-operating characteristics by setting invasive FFR of ≤ 0.80 as objective variable. The positive and negative predictive values of FFR-CT of 0.80 were also evaluated. Results: The median age of the patients was 71 years, and 65.5% of the patients were men. The AUC of the mid-distal FFR-CT was greater than that of the far-distal FFR-CT (0.87 [95% CI, 0.83-0.90] vs 0.81 [95% CI, 0.76-0.85], p < 0.001). The positive predictive value (PPV) of the mid-distal FFR-CT was also better than that of the far-distal FFR-CT (77.7% vs 57.9%), whereas the negative predictive values (NPV) were comparable between the mid- and far-distal FFR-CT (84.5% vs 85.0%). These tendencies were common when coronary arteries were evaluated in each. Conclusions: The far-distal FFR-CT overestimated the presence of ischemia as compared with the invasive FFR. Mid-distal FFR-CT is more accurate than far-distal FFR-CT, and FFR-CT should be measured at the mid-distal site, where the distal sensor of the invasive FFR pressure wire is expected to be placed. [ABSTRACT FROM AUTHOR]

Introduction: The interplay of self-rated health (SRH), Coronary Artery Calcium (CAC) and ASCVD risk is poorly described. We assessed the correlation between SRH and CAC, and whether the combination of SRH and CAC offers similar risk discrimination to established risk scores. Methods: We included 6,764 participants of the Multi-Ethnic Study of Atherosclerosis. SRH was classified as Poor/Fair, Good, Very Good or Excellent. CAC scores were handled in categorical and log-transformed continuous forms. ASCVD risk scores were derived using the Pooled Cohort Equations. Participants were followed over a median of 13.2 years for hard coronary heart disease (CHD) and cardiovascular disease (CVD) events, and all-cause death. We assessed the association of SRH with risk factors and CAC. We then assessed the predictive value of SRH, using Cox regression models sequentially adjusted for age, gender, race/ethnicity; CAC; and risk factors. Similarly, we assessed the predictive value of CAC in the excellent SRH group. Finally, we assessed improvements in risk discrimination on adding SRH to CAC, and compared the discriminatory value of the combination of SRH and CAC to that of the ASCVD risk score. Results: Mean [SD] age was 62.1 [10.2] years, with 47% men. SRH was strongly associated with age, sex, race/ethnicity, healthy diet, physical activity, and cardiovascular risk factors. There was no correlation (r= -0.007, p= 0.57) or association between SRH and the presence or severity of CAC. In models adjusted for age, gender, race/ethnicity, and CAC, those who reported excellent health had 45% lower risk of CVD (HR 0.55, 95% CI 0.39 - 0.77) and 42% lower risk of CHD (HR 0.58, 95% CI 0.37 - 0.90) compared to those who reported Poor/Fair health. CAC was however predictive of risk in all SRH groups, including the excellent SRH group. The addition of SRH to CAC improved ROC c-statistics for all tested outcomes. A comparison of SRH plus CAC vs ASCVD risk score showed similar CHD (0.734 vs 0.712, p=0.09) and CVD (0.706 vs 0.717, p=0.31) risk discrimination. Conclusion: While SRH and CAC similarly integrate risk variables, they are poorly correlated and have predictive utility independent of each other. A simple combination of these measures can be complementary for risk prediction, with similar risk discrimination to the ASCVD risk score. [ABSTRACT FROM AUTHOR]

Introduction: The relation between the frame geometry and transprosthesis gradient of SAPIEN 3 THV after transcatheter aortic valve implantation (TAVI) are still unknown. Hypothesis: In patients with SAPIEN 3 THV, the frame geometry at mid-level might have more influence on transprosthesis gradient than at other levels. Methods: We included consecutive patients from the RESOLVE registry (NCT02318342) that had a contrast computed tomography (CT) and Transthoracic echocardiogram (TTE) at 30 days after TAVI from December 2013 to January 2017. The stent frame of each THV was assessed at 5 cross-sectional levels (inflow-, annulus-, mid-, sinus- and outflow-level). Geometry of the stent frame was assessed for eccentricity (1 - minimum diameter/maximum diameter) and expansion rate (CT derived external valve area/nominal external valve area). We defined high transprosthesis gradient as mean trans-prosthesis gradient ≧20mmHg. Results: A total of 172 patients was enrolled in this study. Measurements of the geometry of SAPIEN3 THV on CT are shown in Table. Multiple regression analysis revealed there were associations between mean transprosthesis gradient, and THV mid expansion (r=-0.26, p=0.0002) and THV outflow expansion (r=-0.095, p=0.013). On the other hand, THV eccentricity at each level did not show association with mean transprosthesis gradient. Among our study populations, 9 patients had high transprosthesis gradient at 30-day follow-up TTE. Based on receiver-operating characteristic curve analysis, expansion rate ≤88.4% at mid-level on post-TAVI CT images was the corresponding cut-off point for high transprosthesis gradient (sensitivity: 55.6%, specificity: 89.3%, area under the curve=0.730, 95% confidence interval: 0.66 to 0.80). Conclusions: Valve expansion at mid-level gave more influence on mean transprosthesis gradient than any other geometries in patients who underwent TAVI with SAPIEN 3 THV. Expansion rate ≦88.4% at mid-level could lead to structural transcatheter valve deterioration after SAPIEN 3 THV implantation. [ABSTRACT FROM AUTHOR]

Background: GlycA is a novel composite biomarker of systemic inflammation that reflects posttranslational glycosylation of acute phase reactants. GlycA has been associated with coronary artery calcium, cardiovascular disease (CVD) events and all-cause mortality. Vascular calcifications outside of the coronary arteries have also been found to be risk markers of CVD and mortality. Whether GlycA is linked to Extra-Coronary Calcifications (ECC) is not well established. Methods: We studied 6,531 MESA participants free of clinical CVD who had plasma GlycA measured at baseline by NMR LipoProfile ® analysis. ECC [calcification in the aortic valve (AVC), mitral annulus (MAC), ascending and descending thoracic aorta (ATAC, DTAC)] was ascertained by cardiac CT scans at baseline and repeated up to ~5-yrs later. We used multivariable adjusted Poisson regression with robust variance estimation to assess associations of GlycA with prevalent and incident ECC. Linear mixed models assessed the cross-sectional and 5-yr change in ECC (log transformed + 1). Models adjusted for demographic and lifestyle factors (see table footnote). Results: The mean (SD) age was 62 (10) yrs; for GlycA 381 (61) μmol/L. 53% were women, 27% Black, 22% Hispanic and 12% Chinese American. In cross-sectional analysis, GlycA was positively associated with prevalent AVC, ATAC and DTAC with adjusted prevalence ratios (95% CI) of 1.08 (1.01-1.14), 1.22 (1.08-1.39) and 1.11 (1.08-1.15), respectively (Table). There was also a significant association between GlycA and baseline extent of both ATAC and DTAC. Longitudinally, GlycA was positively associated with incident MAC and DTAC with incidence ratios of 1.19 (1.04-1.37) and 1.19 (1.09-1.30), respectively. GlycA was also associated with 5-yr change in MAC and DTAC extent. Conclusion: In this diverse cohort free from clinical CVD, we found GlycA was positively associated with prevalent and incident measures of ECC, in particular for progression of MAC and DTAC. [ABSTRACT FROM AUTHOR]

Introduction: Complete ductal tissue resection is crucial to avoid postoperative re-coarctation in patients with coarctation of the aorta (CoA). The synchrotron radiation-based X-ray phase-contrast tomography (XPCT) at SPring-8 (Hyogo, Japan) enables clear visualization of the extension of the ductal tissue. We assessed the histological accuracy of XPCT and 3D extent of the ductal tissue in CoA species. Methods: Nine CoA samples, including the aortic isthmus, ductus arteriosus (DA), and descending aorta, were used. XPCT imaging system was used to obtain 3D images. After scanning, the samples were histologically evaluated via Elastica van Gieson (EVG) staining and immunostaining for Transcription factor AP-2 beta (TFAP2B)—expressed specifically in smooth muscle DA cells. Results: The XPCT sectional images clearly demonstrated the ductal tissue distribution as a low-density area. In comparison with EVG staining, the mass density of the aortic wall positively correlated with elastic fiber formation (R:0.69). Moreover, the expression of TFAP2B was consistent with the area of low-density intimal thickness in XPCT images. Based on 3D assessment, the distance from DA insertion to the distal terminal of the ductal media and intima on the ductal side were 1.73±0.34 mm and 2.82±0.67 mm, respectively. Residual ductal tissue at the distal margin was seen in 2 species. In the short-axis view, 79±18% of the total aortic circumference contained ductal tissue. In 3 species, the entire aortic wall was occupied by ductal tissue (Figure). The ductal intima spread more distally and laterally than the ductal media. Conclusions: The contrast resolution of XPCT images was comparable to that obtained from histological assessments, including DA-specific immunostaining. Using 3D images, complete intimal thickness resection, including the side opposite to DA insertion, is feasible to eliminate remnant ductal tissue and prevent postoperative re-coarctation. [ABSTRACT FROM AUTHOR]

Introduction: Coronary heart disease (CHD) has been considered a strong contributor to Alzheimer's disease (AD). However, cardiovascular imaging biomarkers that can sensitively represent both the progression of subclinical CHD and the development of AD are lacking. Hypothesis: Subclinical CHD burden represents the risk of mild cognitive impairment (MCI), a common precursor of AD. Methods: From 2014 to 2018, 2199 participants (1139 males, age 56 ± 5.8 years, range 45 - 64 years) who had been scheduled for coronary computed tomography angiography (CCTA) were enrolled in the present study. Coronary stenosis scores (CSSs) were calculated for each participant. Each case of mild stenosis (< 50%) was scored 1 point; medium stenosis (≥50% and <75%) was scored 2 points; and severe stenosis (≥75%) was scored 3 points. Coronary artery calcification (CAC) was also graded. An Agatston score of 0 was defined as CAC 0; scores of 1 - 99 were defined as CAC 1; scores of 100 - 400 were defined as CAC 2; and scores > 400 were defined as CAC 3. CAC and CSS, as well as the prevalence of CHD risk conditions, including diabetes mellitus (DM), hypertension (HTN), dyslipidemia, obesity and smoking, were compared between participants with and without MCI. Results: Compared with the participants without MCI, the MCI patients had, on average, higher CAC grades (1.58 ± 0.97 vs. 1.16 ± 0.76, p < 0.001) and CSSs (2.04 ± 1.95 vs. 1.45 ± 1.27, p < 0.001). Severe coronary calcification (CAC 3) was more prevalent among the MCI patients than the controls (20% vs. 4%, p < 0.001). When treating MCI as a neuropathological outcome, CAC, CSS and other CHD risk conditions demonstrated predictive values for MCI. Compared with males, females had a higher risk (odds ratio; OR) of MCI (OR = 1.438, 95% confidence interval [CI] 1.035 - 1.999). When the CAC degree increased from 0 to 3, the OR for MCI was 4.37 (95% CI 2.18 - 8.76). A 1-unit increase in CSS resulted in an increased MCI risk (OR = 1.18, 95% CI 1.03 - 1.34). In addition, the presence of dyslipidemia resulted in an OR of 2.41 (95% CI 1.57- 3.70) for MCI (Figure 1 A-B). Conclusions: CAC and CSS were correlated with MCI risk in a middle-aged population. The CCTA-derived CHD burden has the potential to serve as an early quantitative cardiovascular imaging biomarker for predicting AD. [ABSTRACT FROM AUTHOR]

Background: Coronary artery disease (CAD) is the major cause of mortality and morbidity in pts with diabetes mellitus (DM). It is proposed that 64-slice coronary CT angiography (CCTA) may provide early CAD information on both myocardial ischemia and plaque burden, which could guide preventative therapy and reduce future cardiovascular events in high-risk otherwise asymptomatic DM patients. Methods: A total of 900 participants with high risk DM (males ≥50 yrs / females ≥55 yrs with DM ≥3 years on DM medication ≥1 yr, or males ≥40 yrs / females ≥45 yrs with DM ≥5 yrs on medication ≥1 yr) and no symptoms of CAD were randomly assigned to be assessed by CCTA or not. Pts randomized to CCTA (n=452) were managed by their physicians according to pre-specified trial recommendations based on the results of CCTA screening. Those randomized to the control arm (n=448) received standard medical therapy. Participants were monitored for procedures performed and changes in medical therapy accomplished at one year, and prospectively followed up for 4.0±1.7 years for the combined primary clinical endpoint of death, Ml and unstable angina. Results: Major baseline characteristics included age = 61±8 years, males = 52%, DM duration = 13±10 years, Type I DM = 12%, Insulin requiring = 43%, systolic BP = 130±12 mm Hg, HgA1C = 7.5±1.4% and LDL cholesterol = 87±32 mg/dL. Of those randomized to the screening arm 285(63%) had at least some degree of atherosclerosis and 21 (4.7%) had severe (>70% stenosis) proximal vessel CAD. This resulted in 26 (5.8%) protocol coronary revascularization procedures, more use of statin therapy (83.1% versus 75.7%; p=0.008) and a significant reduction in blood pressure and LDL levels at one year compared to those randomized to control. The primary event rate was 7.6% and 6.2% for non-screened and screened groups respectively (Hazard ratio (HR) = 0.80, p=0.38). Conclusions: In this contemporary study population of patients with high risk, but well medically managed, asymptomatic diabetes, randomization to screening with CCTA resulted in a modest number of protocol recommended coronary revascularization procedures and a significant increase in the use of statin therapy. However, it did not result in a significant reduction in the primary clinical endpoint by 4.0 years. [ABSTRACT FROM AUTHOR]