Risultati per: Prevenzione, diagnosi e gestione delle infezioni cutanee post-operatorie

Circulation, Volume 150, Issue Suppl_1, Page A4146512-A4146512, November 12, 2024. Background:Recent heart failure studies show that post-exercise VO2recovery (VO2Rec) patterns track closely with exercise cardiac output and outcomes, but not with peripheral oxygen (O2) extraction. In patients with obstructive hypertrophic cardiomyopathy (oHCM), studies of VO2Rec changes with effective cardio-specific interventions are lacking. We hypothesized that treatment with aficamten, a next-in-class cardiac myosin inhibitor, would shorten VO2Rec in patients with oHCM.Methods:SEQUOIA-HCM is the pivotal phase 3 trial of aficamten in symptomatic patients with oHCM (New York Heart Association functional class [NYHA FC] II-III, peak VO2[pVO2] ≤90% predicted, respiratory exchange ratio ≥1.05). Patients were randomized 1:1 to aficamten or placebo for 24 weeks with the primary endpoint of change from baseline (BL) in pVO2. For this analysis, VO2Rec was measured as the time taken after exercise cessation for VO2to decline by 12.5% (t12.5%), 25%, or 50% of pVO2. Response rates for achieving clinically meaningful threshold reductions ( >15 seconds) in t12.5%, and correlations with changes in cardiac function (echocardiographic parameters/cardiac biomarkers) were assessed.Results:Among 282 randomized patients (mean age 59.1±12.9 years, 115 female [41%]), 263 (93%) had CPETs at BL and W24 with VO2Rec values as shown (Table). At W24, t12.5%improved by 8sec (95% CI, -12, -5sec, p

Circulation, Volume 150, Issue Suppl_1, Page A4144651-A4144651, November 12, 2024. Introduction:Post-transcatheter aortic valve replacement (TAVR) pacemaker (PPM) implantation is a known complication. Chronic total occlusion (CTO) of coronary arteries is common in TAVR patients and is a marker of advanced coronary calcification. Its influence on the requirement for PPM post-TAVR remains unclear. We investigated the association between pre-existing CTO and the incidence of PPM post-TAVR.Methods:A retrospective cohort study was conducted using the National Inpatient Sample database from 2018-2020 with 205,565 patients who underwent TAVR. Propensity score matching was utilized to create a matched cohort of patients with and without CTO, balancing key variables such as age, sex, elective procedure status, and comorbid conditions (heart failure, arrhythmias, pulmonary circulation disorders, peripheral vascular disorders, and complicated diabetes). Outcomes measured included the requirement for PPM implantation post-TAVR, in-hospital mortality, and major adverse cardiac events (MACE). Weighted samples were utilized and p-value

Circulation, Volume 150, Issue Suppl_1, Page A4141719-A4141719, November 12, 2024. Background:Dual antiplatelet therapy (DAPT) is widely used following percutaneous coronary intervention (PCI), but it can be associated with bleeding events and adverse outcomes during therapy. This study aims to perform a gender-based analysis of the bleeding risk and mortality associated with DAPT following PCI.Methods:On May 15, 2024, we searched the following databases: PubMed, Embase and Cochrane. Our inclusion criteria included any trial or cohort that performed a gender-based analysis of bleeding and mortality outcomes in patients taking DAPT post-PCI. Our outcomes were all-cause mortality, cardiac mortality, and bleeding risk. Bleeding risk was assessed using the Bleeding Academic Research Consortium (BARC) classification, and Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria. We used RevMan with a random-effects model to calculate the effect size, using odds ratios (OR) with a 95% confidence interval.Results:Out of the 1,865 articles searched, only 26 papers were eligible for inclusion and analysis. Nine were randomized controlled trials, and 17 were observational cohorts. The total number of patients was 267,986, of which 203,524 were male and 64,436 were female. There was no significant difference in cardiac mortality between males and females; the OR was 0.88 (95% CI: 0.71-1.08, P=0.22). All-cause mortality was reduced in males compared to females, with an OR of 0.81 (95% CI 0.71-0.92, p=0.002). The BRAC 2-5 classification was less likely in males compared to females, with an OR of 0.81 (95% CI: 0.70-0.94, p=0.005). Similarly, in the BRAC 3-5 classification, there was a significant lower probability of bleeding in male compared to female (OR 0.65, 95% CI: 0.52-0.82, p=0.0002). TIMI major bleeding classification was lower in males compared to females, with an OR of 0.61 (95% CI: 0.42-0.88, p = 0.009). This indicates higher rates of major bleeding in females compared to males; and Similar findings were also observed with TIMI minor (OR 0.65, 95% CI: 0.46-0.92, p=0.01).Conclusions:These findings highlight the disparities in clinical outcomes of dual antiplatelet therapy following PCI. Females had higher rates of significant bleeding events and all-cause mortality compared to males. This underscores the necessity of investigating the underlying mechanisms driving this gap, emphasizing the need for further research in order to understand and address these differences.

Circulation, Volume 150, Issue Suppl_1, Page A4119189-A4119189, November 12, 2024. Background:Direct current cardioversion (DCCV) carries a risk for stroke in AF patients, for that reason there are guidelines for mitigating this risk in AF patients on oral anticoagulation (OAC). Meanwhile, no consensus on the best approach for cardioverting patients with an appendage occlusion device in situ. This led to a very wide variation in pre and post DCCV practices in these patients.Aims:We aim to explore different factors that might be associated with the variation seen in pre-DCCV imaging practices in patients presenting post- percutaneous LAAO.Methods:This was a multi-center retrospective cohort study of patients who received DCCV for AF or AFL during follow up after LAAO procedure within a single healthcare system from 2016-2024.Results:A total of 119 patients were included, there were more females 70 (59%), with more than half (64 (54%)) receiving a first-generation WATCHMAN™ 2.5, while the rest had WATCHMAN FLX™. Median age at presentation was 77 years (72,82), BMI of 31 kg/m2(26,37), average CHADSVASC score of 4.5 and HASBLED score of 3. A median duration of 10 months (3,21) between LAAO to presentation for DCCV . Forty-four (37%) patients had pre-DCCV imaging (imaging cohort). Number of males was significantly higher in the imaging cohort (24 (54.5%) vs 25 (33.3%), p=0.038), compared to those without imaging. There was a significant difference (p

Circulation, Volume 150, Issue Suppl_1, Page ASa1208-ASa1208, November 12, 2024. Throughout the world, neurologically intact survival to discharge remains low. The Joint Commission (TJC) released post resuscitation requirements in January of 2022. Sanford Bemidji reviewed options that would meet the TJC requirements: Transfer the patient or develop a novel way to meet those needs in the current setting. With the latter, the positive impact on patients is significant in that they receive a high care level of care close to home without delay in care.Sanford Bemidji Medical Center is a rural regional 118-bed hospital in Minnesota with a 14-bed Intensive Care unit. We are unique in that despite our size we serve a large regional footprint of over 100,000 people including three Native American reservations. Our objective was to utilize evidence based guidelines to implement a post cardiac arrest care (PCAC) workflow for adult cardiac arrest patients who obtain return of spontaneous circulation (ROSC) by end of first quarter 2023. The project incorporated low cost equipment and staff training. We used the Plan, Do, Study, Act cycle for our methodology. The outcome metric was neurologically intact survival to hospital discharge. Process metrics included placement and use of the ROSC order set, fever avoidance, rapid EEG completed, MAP over 65, and oxygen saturations of 92-98%. Sixty-one adult patients (both in hospital and out of hospital) suffered cardiac arrest at Sanford Bemidji in the 9 months following project implementation in 2023. Demographics included 3 native americans and 2 caucasians, ages 57-73, 3 males and 2 females. Our overall survival rate remained above the national average. For the few patients who met criteria for ROSC interventions, 4 of 5 (80%) received the ROSC interventions, 2 of 4 (50%) survived hospital to discharge neurologically intact. Results showed an increase in maintaining optimal MAP from 81% in 2022 to 100% in 2023 and achieving oxygen saturation parameters 80% of the time in 2023 compared to 66% in 2022. Real time monitoring and coaching of the order set is needed to increase utilization of the order set in full (fever avoidance was at 20% and rapid EEG completed in 40% of cases with a goal of 100% for both).More data is needed to ascertain the outcomes of a ROSC workflow in like sized hospitals with similar resources. The novelty of this innovative project is in the implementation of an evidence based PCAC workflow in a 118-bed rural hospital giving all cardiac arrest patients a chance for a full recovery.

Circulation, Volume 150, Issue Suppl_1, Page A4145096-A4145096, November 12, 2024. Introduction:Postural orthostatic tachycardia syndrome (POTS) and Inappropriate sinus tachycardia (IST) are common manifestations of cardiovascular dysautonomia (CVAD) in patients with post-COVID-19 syndrome. Studies regarding differences between post-COVID-19 POTS and post-COVID-19 IST have been sparse and based on small patient series.Aims:To examine clinical differences between POTS and IST in patients with post-COVID-19 syndrome.Methods:A cross-sectional observational study based on a dataset of patients diagnosed with post-COVID-19 syndrome and POTS/IST, at Karolinska University Hospital, Stockholm in 2020-2023, was performed. Data was retrieved using patients’ medical records. ANOVA, chi-square tests and Fisher’s exact tests were used for analysis.Results:A total of 200 patients diagnosed with post-COVID POTS/IST (ICD-10 codes, I.498 + U.099) were included (female, 85%) and divided into a POTS-group (n=110) and IST-group (n=90). Sixty-one patients (31%) met the diagnostic criteria of both and were included in the IST-group. The mean ages were 38 years for the POTS-group and 42 years for the IST-group (p=0.027). Hypertension was more common within the IST-group (p

Circulation, Volume 150, Issue Suppl_1, Page A4140074-A4140074, November 12, 2024. Background:Long QT syndrome (LQTS) is a potentially lethal cardiac channelopathy. Among women with LQT2, the post-partum period has been considered high risk for cardiac events. However, whether this risk persists after establishing their diagnosis and implementing their LQT2-directed treatment program remains to be determined.Objective:To describe the management and outcomes of LQT2 women during the 9 months post-partum period.Methods:A retrospective analysis of 1869 patients with LQTS treated and evaluated at a tertiary center specializing in Genetic Heart Disease from January 2000 to November 2023 was performed to identify women with diagnosed and treated LQT2 who had a pregnancy during follow-up. Data were abstracted for patient demographics, clinical characteristics, symptomatic status, and treatment plans before and after pregnancy.Results:Overall, 30 pregnancies occurred in 22 women with LQT2. Their average QTc was 489 ± 34 ms with 7 patients (32%) having a resting QTc > 500 ms. Prior to their first post-partum period, 5/22 (23%) were symptomatic with 2 (9%) experiencing a LQT2-triggered sudden cardiac arrest (SCA). Before their post-partum period, their LQT2-directed therapy comprised preventative measures only in 7 (23%), drug therapy in 16 (53%), combination therapy in 7 (23%), and 10 women (43%) had an implantable cardioverter defibrillator (ICD). Pre-emptive treatment intensification was done for 24/30 post-partum periods. Only a single VF-terminating ICD therapy occurred in 1 (3%) of the 30 post-partum periods involving a 21-year-old with p.Lys610Asn-KCNH2 variant, QTc = 490 ms, and a pre-diagnosis presentation of seizures.Conclusion:Although the post-partum period is regarded as a ‘high risk’ window of time for women with LQT2, the risk of a LQT2-triggered cardiac event after diagnosis and implementation of contemporary therapies is very low. This designation of “high risk” among correctly diagnosed and treated women is misleading and generates inappropriate and unnecessary anxiety.

Circulation, Volume 150, Issue Suppl_1, Page A4144690-A4144690, November 12, 2024. Background:High-density lipoproteins (HDLs) have various potentially beneficial circulatory effects. Apolipoprotein A-1, one of the HDL mimetics, has been shown in several studies to slow the progression of atherosclerosis after an acute coronary syndrome (ACS) event.Aim:To evaluate the comparative efficacy of Apo A1 on Total Atheroma Volume (TAV), Percent Atheroma Volume (PAV), and changes in these parameters.Methods:We systematically searched articles in PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase published up to June 2024. Eligible randomized controlled trials (RCTs) enrolled adults who received Apo A1 infusion, compared to placebo, within 2 weeks of an ACS event (defined as unstable angina, non-ST or ST-segment elevation myocardial infarction) or with at least one narrowing of ≥20% on coronary angiography at baseline. Apo A1 infusion preparations evaluated include ETC-216, CER-001, CSL-111, and MDCO-216. Network meta-analysis was performed.Results:A total of 5 RCTs were included in our analysis. Outcomes evaluated include PAV, TAV (measured by intravascular ultrasonography catheter), and changes in these values from baseline to follow-up. For changes in PAV, only ETC-216 45 mg was statistically significant (MD: -12.74, [-20.70; -4.78]). All other regimens were statistically insignificant: ETC-216 15 mg, ETC-216 15 and 45 mg combined, CER-001 3 mg, CER-001 6 mg, CER-001 12 mg, MDCO-216 20 mg, and CSL-111 40 or 80 mg. In addition, changes in TAV showed no significant treatment effects. PAV was lowest at follow-up in the CER-001 3 mg (MD: -1.68, [-4.73; 1.38]) and MDCO-216 20 mg (MD: 1.00, [-3.64; 5.64]) groups; all other ETC-216 and CER-001 regimens were insignificant. For TAV, only MDCO-216 20 mg (MD: -10.00, [-39.58; 19.58]) and CER-001 3 mg (MD: -2.47, [-19.84; 14.90]) showed insignificant treatment effects, while all ETC-216 regimens had no beneficial effect.Conclusion:Our analysis concludes that ETC-216, 45 mg showed a significant reduction in PAV. Other regimens were insignificant in their effect on atheroma reduction. This analysis highlights the need for further clinical trials to explore this regimen for enhancing responses in ACS patients.

Circulation, Volume 150, Issue Suppl_1, Page A4139469-A4139469, November 12, 2024. Introduction:Pulmonary Vein Isolation (PVI) has become the cornerstone during ablation of Atrial Fibrillation. The primary goal of the procedure is to prevent potential arrhythmogenic triggers from accessing the main left atrial substrate. However, incomplete fibrosis leading to PV reconnection has been identified as the primary reason for AF recurrence. It is unclear whether immediate voltage mapping and additional lesions delivered to areas of residual or recovered voltages will improve the outcome. This study evaluates the 1-year success and long-term recurrence-free survival in patients who underwent post-procedure voltage mapping (PPVM) to identify residual Low-Voltage Areas (LVAs) to guide the delivery of additional ablation lesions.Methods:We analyzed 588 patients who underwent PVI from 2015 to 2023. Of these, 243 had PPVM done to determine LVAs and guide additional ablation lesions. The control arm comprised 345 patients who underwent PVI by the same operators without PPVM. The primary endpoints were 1-year success and longer-term recurrence-free survival. Secondary endpoints were the incidence of complications and the prevalence of LVAs in patients who underwent PPVM.Results:Patients who underwent remapping were older than the control arm (68.3 vs 65.6 years, p = 0.005). There were no other significant differences in baseline characteristics between the two groups. At 1-year follow-up, the success rates were 79% in the treatment arm compared to 72% in the control arm (p = 0.038). Patients in the intervention arm had a recurrence-free survival rate of 65% and 54% at 2 and 4 years, respectively, compared to 62% and 43% in the control arm (p = 0.044). The prevalence of LVAs in the treatment arm was 56.8%. Additionally, complication rates were not increased in the remapping arm (3% vs 8%, p = 0.012).Conclusion:PPVM-guided incremental ablation lesions improve the 1-year success rate and recurrence-free survival at 2 and 4 years compared to traditional PVI without increasing complications due to additional lesion delivery.

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.

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

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.

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.

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

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

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.