Risultati per: Probiotici: in vivo vs in vitro

Circulation, Volume 146, Issue Suppl_1, Page A11305-A11305, November 8, 2022. Background:Cholesterol efflux capacity (CEC) is inversely related to incident cardiovascular events. CSL112 (apoA-I (human)) infusion rapidly and robustly increases CEC in AMI patients, but it is unknown whether this translates to increased hepatocyte cholesterol uptake, the subsequent step in reverse cholesterol transport.Purpose:To determine whether CSL112 increases cholesterol uptake by hepatocytes when administered post AMI.Methods:Patients from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) study received either placebo, 2g or 6g CSL112 post AMI. Serum samples from a subset of subjects (n=15 per group) were studiedex vivo. Firstly, CEC was assessed using J774 macrophages loaded with labelled [3H]cholesterol tracer. Cholesterol uptake media (200μL) was then collected and applied to Fu5AH hepatocytes for assessment of labelled cholesterol uptake.Results:CSL112 infusion dose-dependently increased hepatocyte cholesterol uptake, with the 6g dose inducing a < 2-fold increase at the end of infusion (2 h), and sustained elevation above baseline at 24 - 48 h (Fig 1A). Hepatocyte cholesterol uptake across all dose groups and timepoints was strongly correlated with total CEC (r=0.949; p

Circulation, Volume 146, Issue Suppl_1, Page A15363-A15363, November 8, 2022. Introduction:Leadless pacemakers (LP) are a less invasive option compared to conventional transvenous pacemakers (TVP). They were introduced with the hope of eliminating complications associated with TVP and leads, which are more common among the elderly population. However, evidence supporting their use is uncertain. This study aims to compare the safety of the LP compared to TVP in patients 65 and older.Methods:We retrospectively analyzed consecutive patients, aged 65 and older, who were implanted a LP or TVP between August 2017 and November 2021, in 2 experienced Cardiovascular centers. The primary endpoint was a composite of any procedure-related complication (hematoma, venous thrombosis, infections, hemothorax, device dislodgement, pneumothorax). The secondary endpoint was the need for reinterventions.Results:A total of 313 patients were included; 219 received a TVP and 94 patients received a LP. Of the TVPs implanted, 68% used cephalic access, 21% axillary and 11% subclavian. The mean age was 78.9 + 7.76 for the TVP group and 82.6 +8.83 for the LP group. A total of 23 patients in the TVP group reached the primary end point vs 4 patients in the LP group, with a relative risk reduction of 60% of procedure related complications in LP compared to TVP (risk ratio [RR]:0.4; 95% CI (0.144-1.139); P= 0.043). In addition, 8 patients in the TVP group reached the secondary outcome vs none in the LP group (3.65% vs. 0%; p=

Circulation, Volume 146, Issue Suppl_1, Page A9859-A9859, November 8, 2022. Background:The use of colchicine has been associated with reduction of adverse cardiac events in patients with coronary artery disease (CAD). The role of this drug after percutaneous coronary intervention (PCI) with bare metal stents (BMS) has not been evaluated against isolated PCI with drug eluting stents (DES).Aim:The study was designed to test an improved cost-effectiveness with BMS plus colchicine (group BMS+C) compared to DES alone (group DES), provided its noninferiority in terms of major adverse cardiac events (MACE) at 1 year.Methods:This is a prospective, multicenter, randomized controlled trial performed in 4 centers. The trial has been registered at clinicaltrials.gov (NCT04382443). Study protocol and informed consent have been approved by an Independent Ethical and Review Board Committee and were presented to Argentina National regulatory authorities for Health, Technology and Medications. Patients in the BMS+C group received 0.5mg oral doses twice a day of colchicine for 3 months. Outpatient visits were scheduled at 1, 3, 6 and 12 months as well as at 3 and 5 years. Primary endpoints were to compare cost-effectiveness and MACE defined as composite of death, myocardial infarction (MI), cerebrovascular accident and ischemia-driven target vessel revascularization.Results:During February 2020 to April 2022, 412 patients with clinically indicated PCI were randomized in the study. Because 2 patients with COVID 19 at the time of randomization were excluded, the final study population was composed of 410 patients (205 patients in each group). Baseline demographic and angiographic characteristics were well balanced diabetes 19.5% vs 21.4%, Acute Coronary Syndromes 78% vs 75%, ST elevation MI 23% vs 21% multiple vessel CAD 44% vs 46%, culprit left anterior descending artery 58% vs 57.8%, peripheral vascular disease 3.4% in BMS+C and DES groups respectively.2.9% of patients in BMS+C didn’t complete the treatment for side effects (diarrhea). Presently, patients were follow at mean of 381 days ( range 45 to 839),1 -year follow-up was completed in 61%.Conclusion:A 3-month treatment with colchicine after PCI with BMS was feasible and safe. Final 1-year clinical outcomes and cost-effectiveness results will be available at the time of presentation.

Circulation, Volume 146, Issue Suppl_1, Page A12471-A12471, November 8, 2022. Introduction:Ventricular tachycardia (VT) poses a significant risk in patients with ischemic cardiomyopathy. Antiarrhythmic drugs (AAD) and catheter ablation are the 2 strategies employed to reduce the risk of future VT episodes. It is not established if one strategy is superior to the other.Hypothesis:Recently, randomized trials have been published comparing the efficacy and safety of both strategies for VT management. Unfortunately, most of these trials included a relatively small number of patients and had different outcomes or composite of outcomes limiting their utility.Methods:We performed a meta-analysis of randomized clinical trials comparing these treatment modalities for VT management. Criteria for appropriate studies were the inclusion of outcome data for both ablation and AAD arms, history of documented VT or ICD therapy before enrollments, and use of ICD to reliably monitor the incidence. Due to recent advances in substrate-based VT ablation and changes in ICD algorithms we limited our search for studies published in last 10 years. We identified four studies that met our inclusion and exclusion criteria.Results:Our included studies randomized 609 patients, 303 in ablation, and 310 in AAD groups. All-cause mortality data were available for all included studies. The cumulative odds ratio (OR) for all-cause mortality for VT ablation compared to AADs was 0.88, 95% confidence interval [0.56-1.39], p-value 0.58. Cumulative OR for cardiac death was 0.81 [95% CI 0.47-1.38], p-value 0.44, OR for ICD shocks was 0.82[0.57-1.18], p-value 0.29 and the OR for heart failure or cardiac rehospitalization was 0.82 [95% CI 0.53-1.25] p-value 0.35. Treatment-related complications were reported in only two studies with cumulative OR 0.31 [95% CI 0.19-0.51] p

Circulation, Volume 146, Issue Suppl_1, Page A12210-A12210, November 8, 2022. Introduction:Approximately 33% of patients undergoing transcatheter aortic valve replacement (TAVR) have an indication for long-term anticoagulation. In clinical routine, anticoagulation is often discontinued 2 to 4 days before TAVR. The purpose of this meta-analysis was to compare the safety and efficacy of TAVR in patients with per-procedural continuation vs interruption of anticoagulation.Methods:An electronic search was performed using PubMed and Ovid Medline from inception to May 2022. The primary outcome of interest was life-threatening or major bleeding. The secondary outcomes were all-cause mortality, stroke, vascular complications, need for blood transfusion, and closure device failure.Results:Three observational studies were included in our final analysis which consisted of 2,286 patients, with anticoagulation being continued in 1,069 patients and interrupted in 1,217 patients. Although, there was no significant difference in our primary outcome of life-threatening or major bleeding between both groups, there was a trend toward decreased risk of bleeding in patients who were continued on anticoagulation (RR: 0.81; CI: 0.65 to 1.0; I2: 0%, p=0.05). There was a significantly lower risk of stroke (RR: 0.55; CI: 0.35 to 0.88; I2: 0%, p=0.01) and need for blood transfusion (RR: 0.72; CI: 0.59 to 0.87; I2: 0%, p

Circulation, Volume 146, Issue Suppl_1, Page A13695-A13695, November 8, 2022. Introduction:Risk of congenital heart disease (CHD) for in vitro fertilization (IVF) pregnancies is higher than the general population, though other factors may be involved. IVF is an indication for fetal echocardiogram (FE), however there is center variation to perform FE without a secondary indication if the anatomy ultrasound (AU) is normal. We aim to assess the number of new CHD diagnoses following normal AU in IVF-only pregnancies.Hypothesis:We hypothesize that there is minimal benefit to a FE in IVF-only pregnancies with a normal AU and may result in overutilization of resources.Methods:Retrospective chart review from 2016-2021 of all IVF pregnancies with and without a secondary indication for FE at our center. Those without FE during the COVID-19 pandemic were included to assess postnatal CHD detection. Patients were classified as IVF-only if they had a normal AU and no secondary indication for FE; all others classified as IVF+other. Maternal and fetal demographics, AU, FE, and postnatal echo (post-echo) data was obtained.Results:A total of 556 maternal and 628 fetal patients from IVF pregnancies were included; 401 fetuses were IVF-only with a FE, 116 were IVF-only with no FE, the remaining were IVF+other. There was no complex CHD (CCHD) in either IVF-only groups, the FE group detected several minor findings, and the no FE group detected three small septal defects on post-echo (Table 1). The probability of a normal postnatal evaluation in IVF-only with a normal FE was 94% and with no FE was 96%. Minor variations found on FE triggered additional testing (71 total FE in 43 fetuses) and detected a few minor CHD, none requiring intervention.Conclusions:Given low-risk for CCHD in IVF-only pregnancies, there is minimal benefit to a FE in the setting of a normal comprehensive AU and raises questions of cost vs. benefit of FE. This may impact future recommendations for indications for FE in the setting of IVF-only without added risk factors for CHD.

Circulation, Volume 146, Issue Suppl_1, Page A10890-A10890, November 8, 2022. Introduction:The proximal isovelocity surface area (PISA) method has been validated for quantifying severity of mitral regurgitation (MR) in orifices with circular geometry. However, functional MR often has an elliptical orifice, which alters the proximal isovelocity contour from a hemisphere to a hemi-ellipsoid. Studies have previously shown that PISA underestimates regurgitant flow (RF) and effective regurgitant orifice (ERO) in functional MR.Hypothesis:The application of a simplified hemi-ellipsoid formula based on biplane color Doppler improves accuracy in calculating RF and ERO across elliptical orifices.Methods:An in vitro model for flow quantification was used for all experiments. Multiple size orifices with minor to major ratios ranging from 1:1 to 1:9 were constructed by 3D printing. Flow was adjusted at multiple intervals to generate peak flow velocities ranging from 4.1 to 5.5 m/s and aliasing velocities from 12 to 18 cm/s. Isovelocity contours were evaluated by biplane color Doppler (Figure 1A). RF and ERO were estimated using the traditional hemispheric PISA (HS-PISA) formula and a simplified hemiellipsoid formula (HE-PISA) based on two orthogonal diameter measurements (Figure 1A and 1B). The estimated RF and ERO values were compared and validated against those derived from a magnetic flowmeter (FM).Results:Isovelocity contours changed from hemisphere to hemi-ellipsoid orifices with increasing ellipticity ratios. HS-PISA significantly underestimated RF (116 ± 27 vs FM 155 ± 20 ml/s) and ERO (26 ± 4 vs FM 34 ± 1 mm2). Underestimation was significantly reduced by HE-PISA (135 ± 17 ml/s and 30 ± 2.5 mm2, both p

Circulation, Volume 146, Issue Suppl_1, Page A13914-A13914, November 8, 2022. Introduction:Obesity, chronic inflammation, and elevated levels of atherogenic lipids have been associated with increased risk of ASCVD events. Current AHA/ACC guidelines identify existing risk enhancers for ASCVD including persistently elevated LDL-C or triglycerides, chronic kidney disease, chronic inflammatory conditions, and elevated inflammatory markers.Hypothesis:We hypothesized that in a population-level study of adults with diabetes mellitus (DM) without a history of prior ASCVD events, the average body mass index (BMI), hepatic fibrosis score (FIB-4), and neutrophil to lymphocyte ratio (NLR) are higher in the cohort of patients with other, AHA-identified ASCVD risk enhancers.Methods:We performed a hypothesis-driven secondary analysis using a cross-sectional dataset of EHR data from 7 health systems participating in PaTH, a Partner Network in PCORnet. Adults over 40 with DM and without ASCVD were included if they had LDL-c assessed in the most recent year of available data and had >6 months of pre-index data available. We describe cohort-level averages and standard deviations of the most recent lab values and clinical measurements for cohorts with and without AHA/ACC defined ASCVD risk enhancers.Results:We identified 50,749 patients in our baseline risk cohort and 67,593 patients in our enhanced risk cohort across the 7 sites. The enhanced risk cohort had a higher mean (SE) BMI 34.1 (0.28) vs 33.7 (0.29) kg/m2, FIB-4 score 1.5 (0.01) vs 1.4 (0.01) and NLR 62.5 (0.24) vs 61.2 (0.23) compared to the baseline risk cohort. NLR and FIB-4 demonstrated consistently higher averages in the enhanced-risk cohorts across sites.Conclusions:FIB-4 score and NLR both have higher population averages in cohorts with other markers of enhanced ASCVD risk in an adult diabetic patient population. The role of these markers in independently predicting ASCVD risk should be further explored with adjusted analyses in longitudinal datasets.

Circulation, Volume 146, Issue Suppl_1, Page A13724-A13724, November 8, 2022. Introduction.HFpEF is a heterogeneous syndrome, with several underlying etiologic and pathophysiologic factors. As “one size fits all” therapies are not equally efficacious across various HFpEF comorbidities, a precision medicine approach can offer a disease modifying treatment for HFpEF subpopulation stratified for specific molecular targets. Expression of MMP2, 9, and 13 in heart is elevated in HFpEF patients with hypertension, diabetes or coronary disease, and their levels in plasma correlate with survival, suggesting utility as predictive biomarkers. Genetic ablation of MMP2, 9, and 13 leads to a robust antifibrotic effect in the myocardium. Inhibition of MMP2, 9, and 13 directly regulates of Ca2+transients and protects sarcomere function.Hypothesis.We present preclinical profile of VS-041, a novel and narrow-spectrum MMP inhibitor, as a drug candidate for HFpEF patients with elevated levels of MMP2, 9, and 13.Methods and Results.VS-041, optimized with computer-aided drug design methods, shows single-digit IC50against MMP2 (1nM), MMP9 (2nM) and MMP13 (1nM), and maintains >300-fold selectivity against MMP1 and TACE. In isolated cardiomyocytes VS-041 reduces contractility deficit due to fast pacing. With high predicted metabolic bioavailability (MF%=90), >80% target occupancy by VS-041 is estimated after 50 mg/kg PO dose in rats. VS-041 demonstrated robust efficacy in Dahl Salt Sensitive rat model of hypertension and HFpEF after dosing at 25 or 50 mg/kg PO for 5 wks in a therapeutic mode (after 1-wk of high salt lead-in). VS-041 had no effect on blood pressure or ejection fraction confirming a direct effect on diastolic function. In Doppler mitral inflow, analysis of the isovolumic relaxation time and the E/A ratio of peak velocity of filling waves revealed 40% improvement in diastolic function. LV fibrosis was dose-proportionally decreased based on PSR morphometry. No adverse effects were observed after 5 weeks of dosing.Conclusions.Preclinical pharmacology and safety profile of VS-041 support its nomination as clinical candidate and initiation of IND-enabling studies. VS-041 has potential to be first-in-class precision medicine treatment for HFPEF patients with elevated levels of cardiac-relevant MMP2, 9 and 13.

Circulation, Volume 146, Issue Suppl_1, Page A11256-A11256, November 8, 2022. Atherosclerosis begins with endothelial cell (EC) dysfunction. However, the relationship between single-cell (sc) EC profilesin vitroand in human atherosclerotic plaques is unexplored. Herein, we exploited sc EC transcriptomes from human plaques and related them toin vitromodels of inflammation and angiogenesis, which we expected to be relevant. To curate a gene expression profile of ECs found in human atherosclerotic plaques, we performed a meta-analysis of three publicly available human scRNA-seq datasets comprised of 17 coronary and carotid specimens. In parallel, we generated a Multiomein vitrodataset composed of 6 primary human aortic ECs (HAECs), under three experimental conditions: (1) untreated control, and (2) IL-1B-treated (10ng/mL for 1 hour) HAECs on typical gelatin-coated plastic dishes; and (3) untreated HAECs grown on Matrigel to mimic angiogenesis. Five clusters represented the HAECs from all threein vitroconditions. Pathway enrichment analysis revealed that Matrigel-grown ECs (cluster 1) were largely distinguished by Signaling by Rho GTPases, Miro GTPases and RHOBTB3 (R-HSA-9716542; Log10(P) -45.96), while untreated and IL-1B-treated ECs (clusters 0 and 2) were distinguished by regulation of cell adhesion (GO:0030155; Log10(P) -39.92) and Cell Cycle (R-HSA-1640170; Log10(P) -32.2). Of note, clusters 3 and 4 were comprised of HAECs from all 3 conditions and appeared to represent partial and complete endMT, respectively. Cluster 3 and 4 were characterized by greater expression of mesenchymal markers (COL1A1, COL1A2, COL3A1, TAGLN, VIM, and CDH2), while cluster 4 was additionally characterized by a reduction in EC markers (ERG, CDH5, PECAM1). Whenin vitroHAEC andex vivoplaque data were integrated, cells fromin vitrocluster 4 clustered with vascular smooth muscle cells from human atherosclerotic plaques. Taken together, these results reveal that HAECs are heterogeneous bothin vitroandex vivoatherosclerotic conditions. Since endMT occurs spontaneously at some minor frequencyin vitro(~5%) with expression signatures observed in vivo, these data establish a clinically relevantin vitromodel to understand the molecular processes driving endMT.

Circulation, Volume 146, Issue Suppl_1, Page A13618-A13618, November 8, 2022. Background:Daytime extubation post cardiac surgery has been associated with improved hospital outcome in adults. However, data in pediatrics are lacking. We hypothesized that daytime extubations are associated with shorter critical care time (CCT) and investigated the NIH/NHLBI Pediatric Heart Network Collaborative Learning Study (PHN CLS) open database with this goal.Methods:The PHN CLS was designed as a quality improvement project to implement early extubation guidelines in patients (pts) with Tetralogy of Fallot (ToF) and coarctation of the aorta across 10 centers. We included all ToF pts who had complete repair and excluded pts with coarctation, significant comorbidities and who were a part of the clinical practice guideline. Time to extubation (TTE) was assessed by duration and as day (8 am – 5 pm) vs. night (5 pm – 8 am). CCT was defined as the number of hours from ICU handoff to time the pt was medically ready to leave the ICU. Two sample t-tests were used to compare CCTs between day and night extubations. The relationship of TTE in hours and CCT was assessed using linear regression analysis. A sensitivity analysis was performed after exclusion of pts > median CCT of 50 hours.Results:A total of 144 pts (mean age 155 days, range 28-365 days; 59% males) were included. There was no difference in mean CCT for day (n=70) vs. night (n=74) extubations (104.3+18.8 vs. 76.0+9.2 hrs, p= 0.17). Overall, there was a strong correlation between TTE and CCT (r20.88, p

Circulation, Volume 146, Issue Suppl_1, Page A11111-A11111, November 8, 2022. INTRODUCTION:Studies have analyzed contemporary data on outcomes at teaching vs non-teaching hospitals with the results found to be dissimilar in certain procedures in the United States. Coronary Atherectomy (CA) is a minimally invasive procedure that involves the opening of obstruction from heavily calcified blocked coronaries to improve blood flow to the heart. This study is set out to examine the differences in health care outcomes between teaching and non-teaching hospitals in patients who underwent CA using a nationally representative sample.METHODS:We reviewed data from the National Inpatient Sample (NIS) of patients admitted between 2016-2019. Using ICD-10 procedural codes, we identified patients who underwent CA (Rotational or Orbital) within the study period. We further categorized our study population into 2 groups based on teaching vs non-teaching status. Multivariate analysis was done to investigate the in-hospital outcomes between both groups and adjust for confounders.RESULTS:A total of 171,740 CA procedures were performed within the study period. 75% (129,585) vs 25% (42,155) of these procedures were performed in teaching vs non-teaching hospitals respectively. The mean age of patients who underwent the procedure was 65 years, with a higher preponderance in males (71.4%). There was no significant difference in in-hospital mortality in both groups (AOR 1.06, 95% CI 0.93 -1.21, p=0.372). There was also no observed difference in the odds of coronary perforation or cardiac tamponade (AOR 1.26, 95% CI 0.89-1.28 p=0.19) and (AOR 1.23, 95% CI 0.82-1.87, p=0.31) respectively. However, the teaching hospital groups had an increased odds of Coronary dissection (AOR 1.34, 95% CI 1.05 – 1.71, p=0.017) and heart Block (AOR 1.22, 95% CI 1.11-1.34, p< 0.001). We also noticed an increased odds of septic shock (AOR 1.24, 95% CI 1.05-1.80, p= 0.018), AKI (AOR 1.12, 95% CI 1.07-1.22, p=0.005) and a higher hospitalization duration (Adjusted coefficient 0.43, 95% CI 0.30-0.56, p< 0.001) in the teaching hospital group.CONCLUSION:CA performed at teaching hospitals is found to be associated with an increased risk of cardiac (coronary dissection and heart block) and non-cardiac (septic shock and AKI) outcomes.

Circulation, Volume 146, Issue Suppl_1, Page A15631-A15631, November 8, 2022. Background:Functional mitral regurgitation (FMR) is associated with poor prognosis, however the determinants of FMR progression are not well understood. We aimed to determine clinical and cardiac magnetic resonance imaging (CMR) factors associated with FMR progression in patients with non-ischemic cardiomyopathy (NICM) who underwent baseline and follow-up echocardiography.Methods:NICM patients undergoing CMR between 12/2002-12/2017 with baseline (within 90 days of CMR) and follow-up echocardiography were evaluated. Progressive FMR was assessed by echocardiography based on reported FMR severity (none, mild, moderate, moderate-severe, severe). Associations between clinical and CMR parameters (left ventricular and left atrial (LA) size and function, late gadolinium enhancement, and mitral valve (MV) geometry quantification) and progressive FMR were assessed by univariable and stepwise multivariable linear regression.Results:Amongst 311 NICM patients (age 53±15.7 years, female 121 (38.9%)). A total of 17 patients (5.5%) had at least 1-grade of deterioration in FMR, while 66 patients (21.2%) had at least 1-grade of improvement. Univariable and multivariable analyses results are listed in the table. Mean baseline mitral regurgitant fraction by CMR was 14% ± 13%, while the mean of mitral regurgitation severity by echo was in the mild range (1.28 ±1). Baseline FMR grade by TTE (P

Circulation, Volume 146, Issue Suppl_1, Page A12361-A12361, November 8, 2022. Introduction:The efficacy and safety of non-vitamin K oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) at the extremes of body mass index (BMI) and body weight (BW) remains uncertain, leading to concerns regarding use in these populations across clinical practice guidelines.Methods:This analysis of the COMBINE-AF database pools individual patient-level data from the 4 pivotal RCTs of NOAC vs. warfarin in AF: RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48. Pts randomized to low-dose NOACs not globally approved for clinical use were excluded. The primary efficacy and safety outcome was stroke/systemic embolic event (S/SEE) and major bleeding, respectively, with intracranial hemorrhage (ICH) being a secondary outcome. Outcomes were assessed across BMI and BW using a Cox model stratified by trial, with interaction testing for NOAC vs. warfarin. Restricted cubic splines were used to display the hazard ratio of NOAC vs. warfarin for each outcome across BMI.Results:For 58,464 pts, the median BMI was 28 (25th-75th%ile: 25-32) kg/m2,with the top 5% (n=2,924) having a BMI ≥ 40 kg/m2. For patients randomized to warfarin, the risk of each outcome was lower with increasing BMI (HR per 5 kg/m2increase: S/SEE 0.79 [95% CI 0.75-0.84]; major bleeding 0.91 [95% CI 0.87-0.95]; ICH 0.72 [95% CI 0.66-0.80]; p

Circulation, Volume 146, Issue Suppl_1, Page A13685-A13685, November 8, 2022. Introduction:Oxidized LDL triggers inflammation during the initiation and progression of atherosclerotic plaque. The omega-3 fatty acid (n3-FA) EPA administered as icosapent ethyl (IPE), reduced cardiovascular (CV) events in REDUCE-IT due, in part, to potential antioxidant and anti-thrombotic activity. By contrast, mixed n3-FA containing docosahexaenoic acid (DHA) have failed to reduce CV events in similar high-risk patients (STRENGTH). Some have raised concerns over the relationship between these discordant outcomes and placebo choice (mineral oil) as well as DHA content. We compared the effects of these compounds on oxidation of LDL where such ingested fatty acids are concentrated and transported.Methods:LDL was isolated from human plasma by isopycnic centrifugation, separated into test samples of 100 μg/mL, and incubated at 37°C for 30 min with pharmaceutical grade mineral oil, EPA, DHA or vehicle at equimolar levels (10 μM). All samples were then subjected to copper sulfate-induced oxidation (20 μM) monitored by formation of malondialdehyde (MDA). Ascorbic acid at equimolar levels served as a control.Results:LDL oxidation increased 30-fold (0.28±0.03 vs 8.72±0.54 μM;p

Circulation, Volume 146, Issue Suppl_1, Page A14145-A14145, November 8, 2022. Introduction:Atheromatous neovessels with high permeability have been implicated in the evolution of intraplaque haemorrhage (IPH).In vivoquantification of vasa vasorum permeability is possible using dynamic-contrast enhanced-magnetic resonance (DCE-MR) imaging.Hypothesis:In vivorelationship of extent of leakiness of neovessels with critical biomechanical forces i.e. stress and strain in atheroma and with IPH remains unreported.Methods:Patients with mild to severe carotid artery stenosis underwent DCE-MR imaging of their bilateral carotid arteries on a 3 Tesla MR system, using TRICKS method. A two-compartment Patlak model was used to generate a parametric map showing partial plasma volume (vp) and K trans. FEA simulations were performed for stress and strain analyses. For histological analysis, carotid plaques were processed and stained.Results:Sixteen patients underwent carotid MR imaging. The two groups were comparable for their demographics and co-morbidities. Peak structural stress (PSS) and peak strain (P1) were significantly higher in symptomatic versus asymptomatic patients (p=0.002 and 0.009 respectively). Carotid atheroma with IPH had higher PSS and PIcompared to those without IPH [p=0.036 and 0.009]. Variations in stress during one cardiac cycle was significantly greater among plaques with IPH (p=0.01); variation in strain was greater in atheroma with IPH [p=0.04]. AdventitialKtranswas higher in carotid atheroma of symptomatic patients than asymptomatic cohort (p= 0.016). PlaqueKtrans, adventitial and plaquevpwere however comparable for both patient cohorts (p= 0.81, 0.96, 0.36 respectively). AdventitialKtransand plaquevpwere higher in atheroma with IPH (p= 0.04, 0.01) but comparable for plaqueKtransand adventitialvp(p=0.46, 0.88 respectively). A strong correlation was observed between variations in strain during the cardiac cycle with adventitialKtransfor plaques with IPH [Pearsonr: 0.84, p=0.03].Conclusions:A strong correlation exists between adventitial neovessel permeability and variations in strain in atheroma with IPH. Carotid atheroma with IPH have higher biomechanical stresses and strain and variations in these critical biomechanical conditions compared to non-IPH atheroma.