Abstract 4141358: Body weight reduction-associated and -unassociated changes in lipid profile in people with obesity, with or without T2D, treated with tirzepatide: post-hoc analysis of SURMOUNT-1 and SURMOUNT-2

Circulation, Volume 150, Issue Suppl_1, Page A4141358-A4141358, November 12, 2024. Background:Tirzepatide is a once weekly GIP and GLP-1 receptor agonist approved for the treatment of type 2 diabetes (T2D) and obesity. This post hoc analysis evaluated the contribution of body weight reduction-associated and -unassociated effects on the lipid profile of tirzepatide-treated participants living with obesity, without and with T2D, from the SURMOUNT-1 and SURMOUNT-2 clinical trials, respectively.Methods:Participants treated with tirzepatide (pooled doses of 5, 10, 15 mg in SURMOUNT-1 [N=1765] and 10 and 15 mg in SURMOUNT-2 [N=587]) were included in this analysis. The estimated treatment effects and the body weight reduction-associated and -unassociated attribution on changes from baseline in lipid profile (total cholesterol, HDL-C, LDL-C, non-HDL-C, VLDL-C, and triglycerides) at 24 and 72 weeks were assessed via the SAS CAUSALMED procedure.Results:In SURMOUNT-1, after 24 weeks of tirzepatide treatment in participants without T2D, 69-85% of the changes in total cholesterol, HDL-C, LDL-C, and non-HDL-C, and 41-43% of the changes in VLDL-C and triglycerides occurred unassociated with body weight reduction (Table). At 72 weeks, most of the effect on the lipid profile was associated with body weight reduction. In SURMOUNT-2, after 24 weeks of tirzepatide treatment in participants with T2D, most of the changes in the lipid profile occurred unassociated with body weight reduction. At 72 weeks, changes observed in the lipid profile were predominantly associated with body weight reduction, although 43-50% of those changes also occurred unassociated with body weight reduction, except for LDL-C which was almost completely (92%) associated with body weight reduction.Conclusions:In this post hoc analysis from SURMOUNT-1 and SURMOUNT-2, changes in lipid profile were mostly unassociated with body weight reduction after 24 weeks of tirzepatide treatment and associated with of body weight reduction at 72 weeks. Body weight reduction-unassociated mechanisms responsible for the initial changes in lipid profile in participants with obesity treated with tirzepatide warrants further research studies.

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Novembre 2024

Abstract 4138268: The Use of Mavacamten for Management of Post TAVR Obstruction: A Novel Approach to Treatment

Circulation, Volume 150, Issue Suppl_1, Page A4138268-A4138268, November 12, 2024. Background:Treatment of left ventricular outflow tract (LVOT) obstruction involves a combination of negative inotropic agents. However, these therapies have limitations which may result in insufficient control of symptoms, leading to more invasive options such as surgical septal myectomy or septal alcohol ablation. Mavacamten, a cardiac myosin inhibitor, is currently approved for the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). We present a case of a patient treated with mavacamten in addition to β-blockers (BB) for management of post-TAVR LVOT obstruction.Case:A 76 year old female with a past medical history of hypertension, severe aortic stenosis, and coronary artery disease underwent a Medtronic Evolut TAVR in March 2022. Her TTE post TAVR showed LVOT peak gradient greater than 100 mm Hg, LVEF 75% and severe eccentric mitral regurgitation secondary to systolic anterior motion (SAM) of the mitral valve (MV). After multidisciplinary discussion, the patient was discharged on maximally tolerated BB therapy. Follow up TTE showed persistent obstruction and gradients, so diltiazem was added to her regimen. Her subsequent TTE showed a peak LVOT > 100 mmHg at rest, and severe MR. Given persistent findings, she was started on mavacamten, continued on metoprolol, and tapered off of diltiazem. Her TTE two months after initiation of mavacamten revealed resolution of LVOT gradients, reduction of MR to mild and normal LV and TAVR function. She tolerated the therapy well and endorsed ongoing symptomatic improvement on subsequent follow up.Discussion:With the increasing use of TAVR therapy, there has been a corresponding rise in cases of post-TAVR obstruction that must be managed. As demonstrated by this case, management with BB therapy alone may be suboptimal. Although mavacamten is currently approved in patients with HCM, the obstruction in post-TAVR patients is functionally similar. Thus, this medication was trialed as a supplemental treatment in this patient and yielded positive results. This case highlights the potential benefit of extending use of mavacamten alongside β-blocker therapy for this patient population and suggests the need for future studies.

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Novembre 2024

Abstract 4137665: Getting to the Heart of StrokeTM: A Novel American Heart Association Initiative Which Increases Identification of Stroke Etiology and Evidence-Based Post-Stroke Evaluation by Strengthening Cardiology and Neurology Collaboration

Circulation, Volume 150, Issue Suppl_1, Page A4137665-A4137665, November 12, 2024. Background:Nearly one million individuals in the U.S. experience ischemic stroke annually and one-year recurrent stroke risk may exceed 10%. American Heart Association (AHA) Get-With-The-Guidelines-Stroke® Registry (GWTG-S) data suggests that up to 40% of stroke patients are discharged with an undocumented or cryptogenic etiology which may lead to suboptimal secondary prevention. Consequently, improved cardiology and neurology collaboration and evidence-based post-stroke evaluation may help identify stroke etiology, reduce recurrent stroke risk and improve outcomes.Methods:In 2022, the AHA, in collaboration with HCA Healthcare and HCA Healthcare Foundation, designed and launched Getting to the Heart Of StrokeTM(GTTHOS) in 10 HCA Healthcare comprehensive stroke centers to improve: 1) cardiology and neurology stroke care collaboration, 2) evidence-based post-stroke diagnostic evaluation and 3) assessment of social determinants of health and barriers to care. Components included a learning collaborative model, virtual performance improvement consultations, Plan-Do-Study-Acts, multidisciplinary teams, custom and existing GWTG-S metrics and performance improvement feedback.Results:Using existing and custom GWTG-S data, GTTHOS centers increased rates of documented stroke etiology (58.06% vs. 48.63%), while decreasing cryptogenic stroke rates (31.01% vs. 34.89%) and lack of a documented stroke etiology (10.93% vs. 16.48%) (all comparisons on discharge, follow-up vs. baseline, p

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Novembre 2024

Abstract 4135852: Safety and Post-operative Complications of Endovascular Versus Surgical Versus Follow-up and Medical Treatment for Patients with Vertebrobasilar Artery Stenosis: Propensity Score Weighting and a Machine Learning Driven Analysis

Circulation, Volume 150, Issue Suppl_1, Page A4135852-A4135852, November 12, 2024. Background:Vertebrobasilar artery stenosis (VBAS) can cause posterior circulation strokes (PCS). Optimal management is controversial, with options including medical therapy (MT), endovascular stenting (ES), and surgical revascularization (SR). This study compares outcomes of these treatments and evaluates the correlation between clinical features and medical history with 30-day outcome.Methods:Patients with VBAS were identified from the 2017-2018 National Inpatient Sample (NIS). Propensity scores adjusted for baseline differences. Outcomes included mortality, neurological complications (NC), discharge destination (DD), length of stay (LOS), total charges (TC), and procedural complications (PC). Predictive ability of clinical variables was assessed using logistic regression (LR) and machine learning techniques (MLT).Results:Of 1,343 patients, 1,061 (79.0%) received NI, 234 (17.4%) underwent ES, and 24 (1.8%) had SR. Mean age was 69.45 years, with 64.1% male. Demographics: 69.8% White, 14.9% Black, 10.0% Hispanic, and 5.3% other races. Hypertension (HTN, 85.4%) and diabetes (DM, 18.9%) were prevalent. After propensity weighting, ES was associated with higher odds of mortality, surgical/medical complications (SMC), and device/graft complications (DGC) compared to NI. SR showed a non-significant trend toward higher non-home discharges (NHD). ES and SR groups had higher resource utilization with longer LOS and greater TC. Clinical variables alone were weak predictors, with AUC values ranging from 0.454 to 0.71 across different outcomes and models.Conclusion:ES of VBAS was associated with higher mortality and complication rates compared to MT alone, with inconsistent benefits for NC. SR also carried elevated risks without clear advantages over MT. These results support that current clinical independent variables from the NIS are weak predictors. This highlights the limitation of the database in relying solely on clinical and medical history, and suggests that future use of radiological and anatomical features can improve predictions of outcomes and determination of subgroups that can benefit from certain treatment. More studies should be conducted, including post hoc analyses based on radiological and anatomical features, to better inform treatment decisions and determine subgroups that can benefit from intervention or surgery. These findings suggest a need for judicious patient selection and reinforce the role of optimal MT.

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Novembre 2024

Abstract 4144944: Critical Insights for a High-Risk Population: Low Life’s Essential 8 Scores among Post-Operative Coronary Artery Bypass and Percutaneous Coronary Intervention Patients; All of Us Research Program

Circulation, Volume 150, Issue Suppl_1, Page A4144944-A4144944, November 12, 2024. Background:The American Heart Association’s (AHA) Life’s Essential 8 (LE8) concept serves as a quantitative framework for assessing cardiovascular health (CVH). Post-operative coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) patients are at high-risk for subsequent cardiovascular events (CVE). However, LE8 scores for post-procedural CABG or PCI patients remain unknown.Methods:Isolated post-operative CABG (n=208) or PCI (n=739) non-institutionalized patients from the National Institutes of Health’s (NIH) All of Us (AoU) Research Program (2017-2022) were included. LE8 scores (range 0-100, higher = better CVH; excluding diet metric) were calculated using methods recommended by the AHA. Physical activity and sleep metrics were derived from patients’ Fitbit data, while all other metrics were sourced from electronic health records (EHR).Results:Overall LE8 scores for post-operative CABG (57.9 [95% CI: 56.6-59.2]) and PCI patients (55.3 [54.4-56.1]) were significantly lower than that of the general population (65.9 [65.1-66.7] (p

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Novembre 2024

Abstract 4146727: Intensive lifestyle intervention, cardiac biomarkers and atherosclerotic cardiovascular disease in type 2 diabetes and overweight or obesity – a post-hoc analysis of the Look Action for Health in Diabetes (AHEAD) trial

Circulation, Volume 150, Issue Suppl_1, Page A4146727-A4146727, November 12, 2024. Introduction:High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with atherosclerotic cardiovascular disease (ASCVD) risk in type 2 diabetes (T2D). However, the association of longitudinal changes in these cardiac biomarkers with ASCVD risk in T2D is not well-established. Furthermore, the effects of an intensive lifestyle intervention (ILI) targeting weight loss on cardiac biomarkers is not well-characterized.Methods:Participants of the Look AHEAD (Action for Health in Diabetes) trial with T2D and overweight or obesity were included. Hs-cTnT and NT-proBNP were measured at baseline, 1- and 4-year follow-up (Roche Diagnostics). Adjusted Cox models were created to evaluate the associations of baseline, 1-, and 4-year change in cardiac biomarkers with ASCVD risk (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina). The effects of the ILI targeting weight loss versus diabetes support and education (DSE) on cardiac biomarker changes were summarized as the geometric mean ratio (GMR) and 95% confidence interval (CI).Results:Among 3,984 participants with available cardiac biomarker data, there were 771 ASCVD events (median follow-up: 12 years). Higher hs-cTnT and NT-proBNP at baseline were each significantly associated with higher ASCVD risk (Figure 1A). Changes in hs-cTnT and NT-proBNP over 1-year follow-up were not significantly associated with ASCVD risk. However, sustained increases in hs-cTnT and NT-proBNP over 4-year follow-up were each significantly associated with higher ASCVD risk. The ILI versus DSE was significantly associated with lower hs-cTnT at 1- and 4-year follow-up (GMR [95% CI]: 0.96 [0.93-0.99] and 0.94 [0.92-0.97]), respectively) (Figure 1B). In contrast, NT-proBNP increased with the ILI (vs. DSE) at 1-year (GMR [95% CI]: 1.11 [1.05-1.17]), but this difference was attenuated and no longer significant at 4-years.Conclusions:Among adults with T2D, sustained increases in hs-cTnT and NT-proBNP over 4-year follow-up were associated with higher ASCVD risk. An ILI targeting weight loss led to a significant reduction in hs-cTnT and transient rise in NT-proBNP that attenuated over time.

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Novembre 2024

Abstract 4139404: Post-Translational Regulation of Larp6 by IGF-1 Modulates Collagen Synthesis in Smooth Muscle Cells

Circulation, Volume 150, Issue Suppl_1, Page A4139404-A4139404, November 12, 2024. Introduction:Vascular smooth muscle cells (SMCs) play a crucial role in atherosclerosis, contributing to plaque stability by forming the main cellular component of the fibrous cap and synthesizing extracellular matrix. We previously showed that insulin-like growth factor-1 (IGF-1) increases expression of the collagen mRNA binding protein La ribonucleoprotein domain family member 6 (Larp6) and of collagen in atherosclerotic plaques. However, molecular mechanisms remain unclear.Hypothesis:We hypothesized that IGF-1 increases collagen synthesis via a post-translational regulation mechanism of Larp6.Methods:An SMC-specific Larp6 overexpression mouse model (SMC-Larp6) was generated using the Myh11 promoter. Entire aortas and aortic roots were isolated for plaque analysis. IGF-1 was injected in WT mice at a dosage of 1.5 mg/kg. For in vitro assays, human aortic SMCs were transduced with an adenoviral vector to overexpress Larp6 and treated with 50 ng/mL IGF-1 for 18 h.Results:SMC-Larp6 mice had no significant change in plaque collagen content. Additionally, IGF-1 increased Larp6 protein but not mRNA levels suggesting that IGF-1 likely regulated Larp6 via a post-transcriptional mechanism. Western blotting identified two major Larp6 bands at 67 kDa and 70 kDa. We observed a clear band shift from the lower to the upper band after IGF-1 treatment, with a concomitant increase in Procollagen I, suggesting that IGF-1 enhances Larp6’s role in promoting collagen through post-translational modification. Mass spectrometry analysis revealed multiple phosphorylation sites on the LaM and LSA domains of Larp6, including S451, which is phosphorylated by the IGF-1/PI3K/AKT axis. We also observed this protein modification pattern in mouse aortic tissue lysates following IGF-1 injection.Conclusions:IGF-1 regulates Larp6 phosphorylation in SMC, thereby likely playing an important role in IGF-1 induced collagen synthesis. This study provides insight into molecular mechanisms underlying collagen production in SMCs and could inform therapeutic strategies for plaque stabilization.

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Novembre 2024

Abstract 4146283: Infrequent Cognitive Assessments in CABG Trials (from 2005-2023) Highlight Need for Improved Strategies for Cognitive Screening post-coronary bypass grafting (CABG) surgery

Circulation, Volume 150, Issue Suppl_1, Page A4146283-A4146283, November 12, 2024. Objective:The incidence of cognitive decline following coronary artery bypass grafting (CABG) is well-documented, significantly impacting patient morbidity, mortality, and quality of life. We conducted a systematic review that examines cognitive outcomes in CABG randomized controlled trials (RCTs) to identify which cognitive assessments were used, their administration frequency, attrition rates, and their effectiveness in detecting perioperative cognitive changes in control groups.Methods:We conducted a search of MEDLINE, EMBASE, Cochrane Library, and PsycINFO for CABG RCTs that included cognitive assessments, from January 2005 to December 2023. Descriptive statistics were used to summarize the frequency, domains, and attrition rates of each cognitive task. For tasks assessed both pre- and post-operatively in at least three RCTs, control group scores and standard deviations were reported.Results:Out of 3337 screened studies, 2163 were CABG RCTs, and only 69 (3.2%) included cognitive evaluations (Figure 1). These trials involved 15,839 subjects (79% male, mean age 64.4, median follow-up time 90 days) and used 145 unique cognitive tasks. The Trailmaking Test Part B (40/69; 58.0%) and Part A (38/69; 55.0%) were the most frequently used. Only 7 tasks had means and standard deviations reported before and after surgery in more than three RCTs, and none detected significant pre- to post-operative changes. Attrition rates averaged 19.3%, with a wide range from 0% to 62%. Figure 2 demonstrates the decline in cognitive assessments in CABG trials over the years, with a sharp decline after 2014. Trials that assessed cogntion after 2014 tended to favor screening tasks (MMSE/MoCA) alone.Conclusion:Cognitive assessments are infrequent in CABG trials, and existing tests fail to consistently detect cognitive changes. To effectively evaluate and address cognitive impact after CABG, new assessment strategies that are resilient to attrition and practical for use in diverse trial settings are needed.

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Novembre 2024

Abstract 4139977: Aggressive LDL cholesterol lowering post ACS with triple combination therapy: Insights from the multicentric LAI-REACT study

Circulation, Volume 150, Issue Suppl_1, Page A4139977-A4139977, November 12, 2024. Background:Patients with acute coronary syndrome (ACS) face a high risk of recurrent events in the early post ACS period. Rapid reduction of low-density lipoprotein cholesterol (LDL-C) is crucial, but high-intensity statins (HIS) alone often fall short of goals.Research Hypothesis:Early use of triple combination therapy of HIS with non-statin drugs: ezetimibe and bempedoic acid (BA) is likely to help achieving the target goals rapidly.Aim:The LAI-REACT (Lipid Association of India Recommended Early and aggressive lipid lowering in ACS with triple Combination Therapy) study evaluated the LDL-C lowering efficacy of a novel triple combination REB (40 mg rosuvastatin, 10 mg ezetimibe, and 180 mg bempedoic acid daily), in patients with ACS.Methods:The multicentric LAI-REACT study enrolled 369 statin-naïve ACS patients across five Indian centers. All received the triple REB combination upon admission. Lipid profiles were assessed at baseline and weeks 1, 2, 4, and 6.Results:The mean age of the study population was 56.3 ± 11.3 years. The mean LDL-C at admission was 119.2 ± 37.1 mg/dL, which significantly decreased to 49.4 ± 19.3 mg/dL at week 1, 44.7 ± 17.4 mg/dL at week 2, 44.6 ± 16.6 mg/dL at week 4, and 46.7 ± 18.3 mg/dL at week 6. The percentage reductions in LDL-C at weeks 1, 2, 4, and 6 were 58.6%, 62.5%, 62.6%, and 60.8% respectively (repeated measures ANOVA, p

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Novembre 2024

Abstract 4141782: Maladaptive alterations in the biomechanics of the post-myocardial scar as a consequence of CD8+ T-cell transfer

Circulation, Volume 150, Issue Suppl_1, Page A4141782-A4141782, November 12, 2024. CD8+T-cells are adverse regulators post myocardial infarction (MI), leading to increased mortality and impaired cardiac function. We hypothesize that CD8+T-cells impair cardiac function by altering scar composition.MI was induced by ligating the left anterior descending coronary artery in C57BL6/J (WT; 3-7 months of age, n≥2/sex) and CD8atm1makmice (CD8-/-; 3-7 months of age, n≥2/sex/treatment). CD8-/-mice were injected with either vehicle or naïve splenic CD8+T-cells (2x106cells/injection) via tail vein, 4 hours post-MI. Infarct tissue was collected post-MI Day 7 and underwent biomechanical, histological, and biochemical analyses. Effects of granzyme (Gzm) A, B, and K on collagen cleavage were tested using a fluorogenic collagen cleavage assay to examine possible mechanisms of scar alteration.Mice lacking CD8+T-cells had improved ejection fraction and decreased dilation (p

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Novembre 2024

Abstract 4141547: Dietary Branched Chain Amino Acids Modify Post-Infarct Cardiac Remodeling and Function in the Murine Heart

Circulation, Volume 150, Issue Suppl_1, Page A4141547-A4141547, November 12, 2024. Introduction:Branched chain amino acids (BCAAs) are essential amino acids that are elevated in the failing heart and that have been linked with cardiovascular disease risk. Yet, it remains unclear how BCAAs influence the heart after injury. In this study, we examined in mice whether dietary alterations of BCAA levels influences cardiac structure and function after myocardial infarction (MI).Methods and Results:To assess whether altering dietary BCAA levels would impact circulating BCAA concentrations, mice were fed a low (1/3×), normal (1×), or high (2×) BCAA diet over a 7-day period. The low and high BCAA diets were matched for macronutrient content, nitrogen content, and caloric density. We found that mice fed the low BCAA diet had >2-fold lower circulating BCAA concentrations when compared with normal and high BCAA diet feeding strategies (n=8/group; p

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Novembre 2024

Abstract 4119613: Evaluation of Gender, Racial and Ethnic Differences in Time to PCI in the Pre and Post Covid-19 Era

Circulation, Volume 150, Issue Suppl_1, Page A4119613-A4119613, November 12, 2024. Introduction:Percutaneous Coronary Intervention (PCI) is recommended for reperfusion of patients presenting with ST-segment myocardial infarction (STEMI) within 90 minutes. In this study, we sought to identify differences in PCI timing based on gender, race and ethnicity in the pre- and post-COVID era.Methods:We collected retrospective data on 760 patients admitted with STEMI at our quaternary academic medical center from 2018-2022. We defined our binary outcome as time to PCI less than 90 minutes, and adjusted for transfers from outside hospitals. We utilized univariate logistic regression analysis to analyze the association of demographic, clinical, and cardiac catheterization details on our outcome. We then utilized multivariate logistic regression analysis to determine the association of our covariates of interests with time to PCI. The logistic regression model was adjusted for collinearity which were deemed not significant.Results:Among our study population, COVID did not significantly impact whether or not a patient had a diagnostic cardiac catheterization on univariate analysis (OR 2.68, 95% CI 0.61-18.40, p=0.23). However, the post-COVID era was significantly associated with a delayed time to PCI on multivariate analysis [OR 1.62, 95% CI 1.04-2.55, p=0.035) [Figure 1]. In addition, females were 1.8x more likely to have a delayed PCI than males on multivariate regression [OR 1.80, 95% CI 1.10-2.95, p= 0.019) [Figure 1]. Interestingly, on multivariate analysis, females were more likely to have delayed reperfusion in the pre-COVID era (OR 2.92, 1.29-6.77,p= 0.01) but not the post-COVID era (OR 1.54, 0.78-3.06,p=0.2134). Patients in the post-COVID era had increased risk of having their culprit coronary not revascularized on multivariate analysis (OR 2.85, 1.2-8.03, p= 0.03).Conclusions:At our center, COVID did not significantly impact cardiac catheterization rates. However, COVID was significantly associated with delayed reperfusion timing and not revascularizing culprit vessels. Females were much more likely to have a delayed PCI than males in the pre-COVID era which was not seen following COVID-19.

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Novembre 2024

Abstract 4145932: Real World Data From A Nationwide Survey: Current Approaches Post Acute Coronary Syndromes By Cardiologists

Circulation, Volume 150, Issue Suppl_1, Page A4145932-A4145932, November 12, 2024. Background:A new ESC guidelines in 2023, the International Lipid Expert Panel (ILEP) 2021 recommendations, and a subsequent statement by EAS have been published based on recent advances in lipid lowering treatments. However, real world data are lacking regarding the implementation among the community of French cardiologists.Objective:To determine the current approach and therapeutic strategies concerning lipid lowering treatments post-acute coronary syndromes in France.Methods:This national survey was performed during October and November 2023 in France with an online questionnaire on the websites of 2 national French Societies of Cardiologists.Four mailings were sent to cardiologists to invite them to answer to the questionnaire. A total of 400 answers of cardiologists were collected during this 2-month period.Results:For ASCVD patients, cardiologists agreed with an LDL-C goal below 55 mg/dL (1.4 mmol/L) in 69%, below 70 mg/dL (1.8 mmol/L) in 16.5%, and 14.5% between 70 mg/dL and 100 mg/dL (1.8-2.5 mmol/L). An upfront lipid lowering combination strategy using fixed dose combination (FDC) of statins and ezetimibe was prescribed in less than 5% of patients, whereas high-intensity statins were prescribed in more than 90% of patients. No significant differences were observed in terms of sex of patients, geographical area, or strategies followed by male and female cardiologists (p > 0.05). A combination of statins and ezetimibe was prescribed only for a minority of patients, especially as an early upfront strategy. The use of PCSK9i remains marginal and the interval between the ACS and initiation of these medicines remains high.Conclusion:In this contemporary national survey, we report an excellent agreement of lipid goals in secondary prevention by cardiologists. Despite the declared consensus recommending a low LDL-C target in ACS patients, lipid lowering strategies are suboptimal, mainly consisting of high intensity statins. The lack of recommended use of ezetimibe and PCSK9i to lower LDL-C levels highlights the importance of better implementation of intensive and early upfront strategies to reduce recurrent ischemic events.

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Novembre 2024

Abstract 4139933: Hypercholesterolemia and proprotein convertase subtilisin/kexin type 9 potentiate inflammatory response against aortic valve bioprosthetic tissue post-implantation.

Circulation, Volume 150, Issue Suppl_1, Page A4139933-A4139933, November 12, 2024. Introduction:Calcific aortic valve stenosis is the more frequent valvular disease, affecting more than 10% of patients >75 years old. Surgical or transcatheter aortic valve replacement is the only treatment available. There is an increase use of bioprosthetic valves, even if they present a limited durability with the progressive development of structural bioprosthetic deterioration (SVD). Recent clinical studies highlighted an association between circulating lipid factors, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), Lipoprotein (a) and LDL-cholesterol, and SVD. However, the underlying mechanisms remain unknown.Objective:We aim at deciphering the role of hypercholesterolemia and/or PCSK9 on the early processes leading to SVD.Methods:Subcutaneous implantation of bioprosthetic tissue was performed on 10-week old wild type (WT), PCSK9 knock-out (KO) and PCSK9 overexpressing C57BL/6J mice for 28 days. A qualitative anatomopathological score evaluating cell density, infiltration, and tissue degradation was developed. Infiltrated immune cells were characterized by IHC, with a focus on anti- (CD163+) and pro-inflammatory (F4/80+) macrophages, lymphocytes (CD3+) and polynuclear eosinophils (CCR3+).Results:An important infiltration of mononuclear cells into the explanted punches was observed among the 3 groups (n=10 mice/group). Cell recruitment was more pronounced in mice overexpressing PCSK9 compared to WT and KO. The anatomopathological score of PCSK9 overexpressing mice was significantly higher as compared to WT and KO (7.0 [4.1-8.4] vs 4.0 [3.0-4.5] and 2.8 [2.0-3.9], respectively; p=0.008). The infiltrate was mainly composed of macrophages (CD163+ F4/80+) and polynuclear eosinophils, even if few lymphocytes were observed. Polynuclear eosinophils were more abundant in mice overexpressing PCSK9 compared to WT and KO (p=0.01 and p=0.002).Conclusion:Hypercholesterolemia and/or high PCSK9 level promote the cellular response against the bioprosthetic tissue. It potentiates the infiltration of polynuclear eosinophils and macrophages, pointing out for an exacerbated inflammatory response, post implantation. Deeper cellular/molecular analyses are ongoing to provide mechanistic clues to better understand the link between hypercholesterolemia/PCSK9 and the early inflammatory processes leading to SVD.

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Novembre 2024

Abstract 4136346: A Comparative Analysis of Esophageal Cooling for Preventing Esophageal Injury Post Atrial Fibrillation Catheter Ablation: A Systematic Review and Meta-analysis

Circulation, Volume 150, Issue Suppl_1, Page A4136346-A4136346, November 12, 2024. Introduction:Thermal injury following atrial fibrillation catheter ablation is a rare but fatal complication. We aim to assess the safety profile of different forms of esophageal cooling methods versus standards of care.Methods:We searched PubMed, Cochrane Library, Scopus, and Web of Science databases for randomized controlled trials and cohort studies comparing esophageal cooling to Luminal esophageal temperature (LET) monitoring regarding esophageal thermal lesions (ETL) post atrial fibrillation ablation. Case reports, case series, reviews, conference abstracts and animal studies were excluded. Review manager software (version 5.4) was used to perform the meta-analysis.Results:We included 10 studies with 25662 patients in total: 14515 patients in the esophageal cooling group and 11147 patients in the LET group. Overall esophageal lesion analysis demonstrated no statistically significant difference between the esophageal cooling group and LET (RR = 0.72, 95% CI = 0.35 to 1.49, p-value = 0.38). Subgroup analysis showed no statistically significant difference for mild/moderate lesions (RR = 1.52, 95% CI = 0.80 to 2.90, p-value = 0.20). However, the subgroup analysis showed a statistically significant association between esophageal cooling and decreased severity of esophageal lesions compared with LET (RR = 0.29, 95% CI = 0.12 to 0.71, p-value = 0.007). Regarding AF recurrence, the pooled analysis showed no statistically significant difference between esophageal cooling group and LET (RR = 1.24, 95% CI = 0.95 to 1.61, p-value = 0.11).Conclusion:In patients undergoing AF catheter ablation, the implementation of esophageal cooling showed statistical significance in decreasing the severity of esophageal lesions compared to the LET group. Also, esophageal cooling demonstrated non-inferiority in AF recurrence compared to LET. Future research should focus on assessing the long-term effects of esophageal cooling during AF catheter ablation.

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Novembre 2024

Abstract 4148133: Association between small pre-implant left ventricular end diastolic diameter and post left ventricular assist device implantation all-cause mortality: A systematic review and meta-analysis

Circulation, Volume 150, Issue Suppl_1, Page A4148133-A4148133, November 12, 2024. Background:Left ventricular assist devices (LVADs) are crucial for the management of advanced heart failure patients acting, both as a bridge to heart transplant or destination therapy. Existing studies revealed mixed results on the impact of pre-implant left ventricular end-diastolic diameter (LVEDD) on post-LVAD mortality. Some studies found smaller LVEDD increases mortality, while others revealed no significant impact. Due to the limited evidence, this meta-analysis aims to determine the association between pre-LVEDD and post-LVAD implantation mortality through a systematic review and meta-analysis.Method:We systematically reviewed articles until May 2024 examining the association between pre-implant LVEDD and post-LVAD implantation mortality using PubMed, Google Scholar, Embase, and Scopus. A random effects model was used to calculate the pooled adjusted odds ratio (aOR). We used I2statistics to determine the heterogeneity of studies. Leave-one-out sensitivity analysis was done to evaluate each study’s effect on the overall estimate, with statistical significance set at p

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Novembre 2024