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

Circulation, Volume 150, Issue Suppl_1, Page A4139209-A4139209, November 12, 2024. Background:There has been growing awareness and recognition of discrepant health outcomes based on ethnic and racial background in patients undergoing cardiovascular procedures. Transcatheter aortic valve procedures has become the primary treatment for aortic stenosis and is currently the standard of care. Despite widespread adoption of TAVR, African Americans (AA) have continued to remain underrepresented and typically suffer poorer outcomes. Thus, we conducted a systematic review and meta-analysis to compare TAVR outcomes between AA and non-AA populations.Methodology:We systematically searched all electronic databases (PubMed, EMBASE, Scopus, Web of science) from inception until May 25th, 2024. A pooled analysis of data from observational studies and randomized controlled trials reporting post-TAVR outcomes based on racial background were included. The key endpoints evaluated were in-hospital mortality, post-procedure myocardial infarction (MI), pacemaker placement, in-hospital stroke, vascular complications, major bleeding, acute kidney injury (AKI). We used the I2 statistic to assess heterogeneity among studies using the Random-Effects model, with significance set at I2 > 50%. All analysis was carried out using R version 4.3.2.Results:The meta-analysis of eleven observational studies, involving 953,892 TAVR patients [912,301 (95.64%) Caucasians and 41,591 (4.36%) AAs], showed a statistically significant higher risk of post-procedure pacemaker placement (OR 1.08, 95% CI: 0.77-1.51, p=

Circulation, Volume 150, Issue Suppl_1, Page A4140204-A4140204, November 12, 2024. Background:Oxidized phospholipids (OxPL) are preferentially carried by and contribute to the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPL can be quantitated on all apolipoprotein B-100 containing lipoproteins (OxPL-apoB), a dominant proportion of which are present on Lp(a) particles.Objectives:To assess the effect of PCSK9 inhibition by alirocumab on plasma levels of OxPL-apoB, and the relationship to Lp(a) and major adverse cardiovascular events (MACE) in patients with a recent acute coronary syndrome (ACS) on optimized statin treatment.Methods:OxPL-apoB (Diazyme, Inc) and Lp(a) (TinaQuant, Roche Diagnostics) were measured at baseline (1-12 months after ACS) in a subset of participants in the ODYSSEY OUTCOMES trial with samples available at baseline (prior to randomization to alirocumab or placebo, n=11,630) and log2-transformed. Proportional hazards models adjusted for 12 baseline covariates evaluated the association of predictor variables (OxPL-apoB and Lp(a)) with MACE (coronary heart disease death, non-fatal MI, ischemic stroke, and hospitalized unstable angina) and all-cause death, with HRs for doubling of the predictor variable.Results:Baseline OxPL-apoB correlated with Lp(a) (r=0.68, p

Circulation, Volume 150, Issue Suppl_1, Page A4143328-A4143328, November 12, 2024. Background:Direct current cardioversion (DCCV) carries a risk of stroke in atrial fibrillation (AF) patients. Hence, published guidelines for mitigating this risk with oral anticoagulation (OAC). There is no consensus agreement on the safest approach when cardioverting patients with left atrial appendage occlusion device in situ.Aims:We aimed to compare association of pre-DCCV imaging with safety and outcomes in patients with WATCHMAN™ undergoing elective DCCV for atrial arrhythmias (AA)Methods:This was a retrospective cohort study of patients who received DCCV for AA during follow up after LAAO procedure from 2016-2024 within a large health care system. Safety endpoint was freedom from stroke, all-cause mortality, device embolism, and systemic embolism within 30-days post DCCV. Significant peri-device leak (PDL) was defined as > 5mm on cardiac imaging.Results:A total of 119 patients were included, 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. There was a median duration of 10 months (3,21) between LAAO to presentation for DCCV .Forty-four (37%) patients had pre-DCCV imaging, while 75 patients did not receive pre-procedural imaging. Between the two groups, there was no significant difference in OAC (VKA-antagonist/DOAC) usage prior to presentation (8 (18.6%) vs 12 (16.4%), P=0.9), with single antiplatelet therapy was the prevalent anti-thrombotic regimen. There was no significant difference in CHADSVASC, HASBLED, age, LVEF, or timing of presentation relative to the LAAO procedure. Higher percentage of patients were discharged on OAC post DCCV in the imaging cohort (13 (30.2%) vs 14 (19.4%), p=0.27), the difference was not significant. No Device related thrombus (DRT) nor significant PDL was detected on imaging. But non-significant PDL ranging from 2mm-4.7mm was found in 8 (18.1%) out of 44 patients who had imaging prior to DDCV. Safety endpoint was achieved in both cohorts with zero adverse events occurring during the 30 day follow up period post-DCCV.Conclusion:Elective cardioversion for atrial arrhythmias is safe in patients with WATCHMAN™. There were no post-DCCV stroke events in the overall cohort and no DRT identified in the pre-DCCV imaging subgroup. Further studies are needed to determine when pre-DCCV imaging is warranted in this population.

Circulation, Volume 150, Issue Suppl_1, Page A4125636-A4125636, November 12, 2024. Background:Postural orthostatic tachycardia syndrome (POTS) is a prevalent cardiovascular disorder after COVID-19 infection. Although POTS is characterized by the presence of sinus tachycardia, other hemodynamic disturbances including blood pressure (BP) regulation, remain largely unexplored.Aims:We investigated BP changes using 24-hour ambulatory-BP-monitoring in patients with new-onset POTS after COVID-19 compared with pre-pandemic healthy controls.Methods:We performed a case-control study in 100 verified COVID-19 patients with new-onset POTS (mean age 40.0±12.9 years, 85% women) diagnosed by positive head-up tilt-testing versus 100 healthy controls (mean age 45.0±14.6 years, 70% women) from a population-based cohort with negative active standing test, no history of syncope, orthostatic intolerance, or endocrine disease. We analyzed 24-hour Systolic BP (SBP) and hypotensive SBP episodes (

Circulation, Volume 150, Issue Suppl_1, Page A4142740-A4142740, November 12, 2024. Background:Hyperactivation of the left stellate ganglion (LSG) is a key link in the occurrence of ventricular arrhythmias after myocardial infarction (MI). It is reported that neuroimmune interaction based on the depleting of macrophages modulated the overactive neural activity. However, exogenous macrophage scavengers, which is the common depletion strategy in animal models, are hardly capable of depleting the target cells selectively in certain tissues and transient control performance. Consequently, a degradable nanocomposite (PPSM@CS/DSS) were fabricatedto deplete M1 macrophages selectively in LSG and further inhibit the overactive LSG neural activity after myocardial infarction.Hypothesis:In this study, we constructed a degradable nanocomposite with dual functions of targeting M1 macrophages and oxygen-independent PDT-mediated neuroimmune modulation, which isanticipated to deplete M1 macrophages selectively in LSG and further inhibit the overactive LSG neural activity after myocardial infarctionfor prevention and treatment of ventricular arrhythmias post MI.Methods:The prepared nanocomposite material, which is capable of targeting M1 macrophages and oxygen-independent PDT-mediated neuroimmune modulation, was slowly microinjected into LSG of Beagle dogs. The effectiveness and safety of this method based on apoptosisof M1 macrophagesby oxidizing active species was explored and the mechanism of prevention as well as treatment of malignant arrhythmias were discussed. M1 macrophages were selectively apoptotic in the LSG after myocardial infarction under the irradiation of near infrared light.Results:PPSM@CS/DSS is a core-shell structure with a particle size of about 50nm. The PPSM@CS/DSS nanocomposites exhibits band adsorption between 200-900 nm with a pronounced peaks at 650 nm.Cell experiments showed that PPSM@CS/DS was targeted and mainly induced apoptosis of M1 macrophages under 650nm near-red light, but did not significantly increase apoptosis of neuronal cells. PPSM@CS/DSS significantly reduced LSG activity and the incidence of malignant arrhythmias after MI in Beagle dogs under the action of 650nm light.Conclusion:An innovative nanomaterial for regulating LSG through depletion M1 macrophages selectively in LSG is developed to prevent and treat malignant arrhythmias after myocardial infarction.The implementation of this work will provide a novel neural modulation strategy for preventing ventricular arrhythmias.

Circulation, Volume 150, Issue Suppl_1, Page A4125667-A4125667, November 12, 2024. Background:Renal denervation (RDN) has been shown in randomized trials to improve blood pressure compared with a sham procedure. Currently, there are two FDA-approved RDN devices in the United States (US). While nearly half of the US population has hypertension (HTN), the number of patients who may benefit from RDN therapy remains uncertain. In this study, we used a nationally representative dataset to approximate the proportion of patients with HTN who may be eligible for consideration of RDN based on selective criteria.Methods:All adult patients with HTN who participated in the National Health and Nutrition Examination Survey (NHANES) between the years 2009-2020 were identified. We characterized the proportion of these participants that met eligibility criteria based on 1) the FDA indication, 2) the SCAI 2023 RDN position statement, and 3) enrollment criteria from the RDN on-medication randomized trials. National estimates were obtained utilizing survey weighting from the NHANES multistage probability survey design.Results:In total, we identified 16,677 patients with HTN in the US, representing a weighted total of 113,786,149 patients (Table). Using the FDA indication, 31.6% (95% CI, 30.7%-32.6%) of patients meet eligibility criteria for RDN, corresponding to 35,988,870 US adults. By the SCAI 2023 position statement selection criteria, 21.5% (95% CI, 20.7%-22.3%) of patients are eligible for consideration of RDN. Based on enrollment criteria from the RDN on-medication randomized trials, 2.05% (95% CI, 1.81%-2.33%) of US adults meet eligibility for consideration of RDN (Figure).Conclusions:Our findings indicate that nearly one third of US adults with HTN are eligible for consideration of RDN based on the FDA indication; however, a smaller proportion of patients would be eligible based upon society recommendations and randomized trial inclusion criteria. Future studies are needed to further inform which patients will best benefit from this intervention.

Circulation, Volume 150, Issue Suppl_1, Page A4138964-A4138964, November 12, 2024. Background:Post-ablation atrial fibrillation (AF) inducibility has been associated with AF recurrence and is often used as an endpoint for Pulmonary Vein Isolation (PVI). Little is known regarding factors affecting inducibility after PVI, as AF inducibility is common even after PV isolation. Prolonged episodes of untreated AF can result in remodeling of the atrium and the formation of new arrhythmogenic substrate, which may make treatment of AF more challenging. We hypothesized that longer diagnosis-to-ablation time (DAT) is associated with higher rates of post-PVI AF inducibility.Objective:To evaluate DATs in cases of inducible vs. non-inducible AF post ablation.Methods:A single-center, retrospective analysis of 168 consecutive patients who underwent 1sttime PVI between 1/1/2022 and 12/01/2023 was performed. Following PVI, inducibility of AF was tested by programmed stimulation using decremental pacing in 50ms windows for 10 seconds each (from 400 ms down to 200 ms or until loss of 1:1 atrial capture). Results were categorized by type of rhythm induced (non-inducible, AF) and duration (sustained, non-sustained). DAT was obtained from review of the medical records. Descriptive statistics were used to compare demographics and AF type, and parametric and non-parametric tests were used for analysis of the diagnosis-to-ablation window and its relationship to inducibility.Results:There was no difference in demographic data or AF type between the two groups. 85 patients (50.6%), had no inducible AF. 83 out of 168 cases (49.4%) had inducible sustained AF. Overall DATs ranged from 0 to 40 years. DAT was significantly higher in the inducible vs. non-inducible groups (3.810 vs. 2.906 years, p=0.023).Conclusion:Longer DAT is associated with AF inducibility post-PVI despite successful ablation. This association may reflect the increased persistence of AF as it progresses over time. Future studies are needed to evaluate the clinical implications of DAT times.

Circulation, Volume 150, Issue Suppl_1, Page A4140452-A4140452, November 12, 2024. Background:The recent REDUCE-AMI trial showed no benefit to beta-blockers (BB) for patients post-myocardial infarction (MI) with preserved ejection fraction (EF≥50%). Target doses were metoprolol 100 mg and bisoprolol 5 mg daily (50% of the target doses used in the initial randomized clinical trials [RCTs] of BB post-MI).Research question:Do lower BB doses improve survival in post-MI patients with EF≥50%?Aims:To compare the effect of BB dose on all-cause mortality post-MI in patients with EF≥50%.Methods:This is a sub-study from the OBTAIN prospective multi-center registry. Of 7057 patients enrolled with acute MI, 3402 with EF≥50% were discharged alive (age:62.5±13.4 years, 67% male, 28% diabetics, length of stay 6.1±6.0 days). Discharge BB dose was indexed to the target daily BB dose used in RCTs, reported as %. Dosage groups were >0-12.5%, >12.5-25%, >25-50%, and >50% of the target dose. Follow-up vital status was obtained by chart review, Social Security Death Index, or direct contact up to 3 years post-MI. Kaplan-Meier (KM) method was used to calculate three-year survival. Cox proportional hazard regression model was used to identify significant predictors and conduct univariate and multivariate analysis.Results:The KM 3 year survival estimates were 89.0% and 84.3% for patients on and off BB, respectively (unadjusted hazard ratio (HR)=0.66, p=0.012; adjusted HR=0.52, p=0.18). The KM 3 year survival estimates(figure) were 89.8%, 91.0%, 87.9%, and 83.1% for patients on >0-12.5%, >12.5-25%, >25- 50%, and >50% of the BB target dose (unadjusted HR of 0.58, p=0.007; 0.58, p=0.003; 0.70; p=0.066; and 0.98, p=0.93), respectively, compared to no BB. After multivariate analysis, BB target dose showed similar trend, but not statistically significant (adjusted HR=0.65, p=0.46; 0.42, p=0.13; 0.53, p=0.31; 1.01, p=0.92).Conclusion:In OBTAIN, patients treated with low dose BB (≤25% of the target dose) had improved survival post-MI. As this dose was not studied in REDUCE-AMI, these findings are complementary and confirm only that high dose BB therapy provides no benefit post-MI in patients with preserved EF. RCTs to assess the benefit of low dose BB therapy post-MI with preserved EF are needed.

Circulation, Volume 150, Issue Suppl_1, Page A4140906-A4140906, November 12, 2024. Background and Aims:Functional complete revascularization (FCR) subsequent to percutaneous coronary intervention (PCI), as assessed by the residual functional SYNTAX score (rFSS), has been correlated with enhanced prognostic outcomes. This study sought to comprehensively apprehend the adverse cardiovascular prognosis within diabetic cohorts, determining what extent the association of diabetes with clinical outcomes is explained by functional revascularization.Methods:A total of 1,555 patients with available post-PCI quantitative flow ratio (QFR) were included, whose data were collected from PANDA III trial (Figure 1). FCR was defined as rFSS = 0, while anatomic complete revascularization (ACR) was defined as residual SYNTAX score (rSS) = 0. Firstly, we determined the ACR and FCR among DM and non-DM cohorts. Second, multiple cox regression was used to screen for potential mediating variables. Finally, we used structural equation modeling to analysis whether FCR explained the relationship between DM and the risk of 2-year rates of major adverse cardiac events (MACE).Results:Patients with DM had a significant lower percentage of FCR (71.9% vs 80.2%, P

Circulation, Volume 150, Issue Suppl_1, Page A4126893-A4126893, November 12, 2024. Background:Suboptimal medication management is common in patients with heart failure (HF), particularly during transitions-of-care. To date, there are few studies assessing the feasibility of a nurse-pharmacist post-discharge telehealth service for medication optimisation in patients with HF. We performed a feasibility study to determine service uptake and acceptability, and ability to identify medication-related issues for HF patients as they transition from hospital to home.Methods:HF patients were referred to an existing post-discharge telehealth service and offered medication reconciliation and education in addition to their usual care; a service we termed ‘MedRec’ (MR). Primary outcomes were feasibility, measured through recruitment and successful MR completion, and acceptability, measured by an investigator-developed survey. Secondary outcomes were medication-related issues detected during MR.Results:A total of 100 HF patients were offered a post-discharge MR. Mean age of patients was 68.5 ±14.2 years, and mostly male sex (62%). Pharmacist MRs were requested by 80% of patients. In total 62 MRs (77.5%) were performed; 9 patients declined MR during follow-up and an additional 9 patients were uncontactable. Mean time to MR following nurse referral was 10.98 ±9.74 days. Drug-related toxicity or adverse effect presentation was identified in 25 (40.3%) MR recipients at the time of consultation and subsequently required general practitioner follow-up. Medication compliance issues were detected by the pharmacist in 13 (20.9%) patients; forgotten doses being the most common concern. Undertreated medical conditions, such as symptomatic HF and chronic pain, were identified in 12 (19.3%) MR recipients. Medications prescribed without any apparent indication were found in 8 (12.9%) patients. Drug or disease management information was requested by 35 (56.4%) MR recipients. A total of 35 (56.5%) post-MR surveys were successfully completed. All participants who completed a post-MR survey agreed that a post-discharge telehealth MR was an acceptable form of education provision. Engagement with a pharmacist MR was perceived to ease anxiety associated with understanding medication-related changes and empowered greater medication self-management.Conclusions:A post-discharge nurse-pharmacist telehealth service is a feasible and acceptable model of care. Inclusion of a routine MR post-discharge may be an effective means of maintaining continuity of care for HF patients.

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.

Circulation, Volume 150, Issue Suppl_1, Page A4146276-A4146276, November 12, 2024. Background:The first-ever genetically modified porcine-to-human cardiac xenotransplantation was performed in January 2022 at the University of Maryland, with the recipient surviving 60 days.Aim:Characterize trends in conduction delay observed over the 60-day post-operative course of the first-ever porcine-to-human cardiac xenotransplant recipient.Methods:Daily 12-lead ECGs were evaluated for presence and type of conduction delay. Over the post-operative period, 93 ECGs were obtained. ECGs that could not be assessed for conduction delay due to presence of significant artifact (2 ECGs) or paced rhythm (12 ECGs) were excluded from evaluation.Results:During the 60-day postoperative period, the xenotransplant exhibited alternating conduction block including nonspecific intraventricular conduction delay (NSIVCD), right bundle branch block (RBBB), incomplete RBBB, and left anterior fascicular block (LAFB). Nonspecific intraventricular conduction delay (NSIVCD) was observed on 6 days in total, occurring primarily within the first 9 post-operative days. After day 9, the conduction block alternated between bifascicular block with RBBB+LAFB, incomplete RBBB+LAFB, RBBB, and incomplete RBBB. The predominant pattern of conduction delay was bifascicular block with RBBB+LAFB, occurring over 32 days in this period. Presence of incomplete RBBB+LAFB was noted on 17 days in total. Isolated RBBB occurred on 2 days, and incomplete RBBB on 4 days. There was no evidence of high-grade atrioventricular block observed in this period.Conclusion:Ventricular conduction in the post-operative period of the first porcine-to-human xenotransplant was characterized by an alternating conduction block with NSIVCD in the early postoperative period (through day 9), followed by predominantly bifascicular block with RBBB and LAFB or incomplete RBBB and LAFB. Atrioventricular conduction remained largely intact without evidence of high-grade AV block nor dependence on back-up pacing during the majority of our patient’s post-operative course.

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

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

Circulation, Volume 150, Issue Suppl_1, Page A4139241-A4139241, November 12, 2024. Background:Percutaneous coronary intervention has significantly improved the prognosis of STEMI, though there is still the risk of fetal mechanical complications, particularly cardiac rupture(CR), which remains an international clinical problem unresolved.Hypothesis:We hypothesized that the combined triple medical therapy(ANT) withAtorvastatin,Nicorandil and Chinese patent medicineTongxinluo(TXL) could be effective in post-infarction CR precautions via significantly inhibiting macrophage activation and secondary ferroptosis of cardiac fibroblasts(CFs) through TRAF6/NF-κB/C/EBPβ pathway.Methods:The 14-day survival and CR rates of AMI mice treated with Atorvastatin, Nicorandil and Tongxinluo, singly or in dual and triple combination, were all compared via the Kaplan-Meier curves. Then the inflammation level and infarct region were measured via ELISA, immunoblot and histopathology. Sequentially immunoprecipitation, luciferase report gene and transcriptome sequencing were introduced to understand the role of the TRAF6/NF-κB/C/EBPβ pathway and its upstream micro-RNAs in CR prevention. Further,in-vitroexperiments were performed to demonstrate the crosstalk between macrophages activation and CFs ferroptosis in CR prevention.Results:Among all therapies involved, the triple combined ANT therapy supremely reduced the incidence of post-infarction CR (from 26.7% to 10.0%) and the mortality of AMI (from 30.0% to 13.3%), during which macrophages reduced most nuclear NF-κB p65 and C/EPBβ by nearly 70% simultaneously through miR215-5p-, miR122-5p-, miR-299b-3p-mediated TRAF6 inhibition, with 50%+ MMP9 cut and more extracellular matrix remaining, especially collagens, Syndecan-1, Laminin and Agrin. And, with the ANT administration, only 20% macrophages remained in peri-infarct areas, accompanied by the lowest serum inflammatory level. Furthermore, CF ferroptosis alleviated most, evidenced by the 4-fold GPX4 and 3-fold FSP-1 up-regulation. Two independent anti-ferroptotic system, GPX4 and FSP-1, worked equally in the nicorandil effect on CF survival, however, with GPX4 or FSP-1 overwhelmingly underlying atorvastatin or Tongxinluo protection against CF ferroptosis respectively.Conclusions:Our results indicated the ANT combination upmost alleviated the excessive excitation of M1 macrophages and its induced CF ferroptosis via prohibiting TRAF6-mediated NF-κB and C/EBPβ translocation, and facilitated myocardial repair to prevent post-infarction cardiac rupture onset.

Circulation, Volume 150, Issue Suppl_1, Page A4138062-A4138062, November 12, 2024. Introduction:Histone deacetylase (HDAC) 6 functions to remove acetyl groups from lysine residues on histone and non-histone proteins. We showed that the augmented activity of HDAC6 in diabetic mice undergoing myocardial ischemia/reperfusion injury (MIRI) was associated with mitochondrial damage. However, it remains unclear how the inhibition of HDAC6 activity affects post-MIRI cardiac remodeling and function in type 2 diabetes.Hypothesis:HDAC6 inhibition suppresses adverse cardiac remodeling and improves mitochondrial dynamics and cardiac function after MIRI in type 2 diabetic mice.Methods:Type 2 diabetic db/db, db/+, and C57BL/6 mice underwent coronary artery occlusion for 20 min followed by reperfusion. Tubastatin A, a selective inhibitor of HDAC6, was injected intraperitoneally 60 min before coronary artery occlusion and once daily after surgery. Mouse hearts were evaluated with echocardiography 28 days after surgery. Myocardium was imaged using electron microscopy, and the expression of mitochondrial dynamin-related protein 1 (DRP1) and fission 1 was measured by Western blotting analysis. H9c2 cardiomyocytes were subjected to hypoxia for 3 hours followed by normoxia for 24 hours in the presence of 5.5- or 25.0-mM D-dextrose and tubastatin A or vehicle.Results:There were no significant differences in the activity of HDAC6, left ventricular diameters and fractional shortening, mitochondrial density volume and surface area, and the ratios of DRP1/GAPDH and fission 1/GAPDH between the db/+ and C57BL/6 groups. Compared to both db/+ and C57BL/6 groups, HDAC6 activity was lower, left ventricular diameters at both end diastole and end systole were longer, fractional shortening and mitochondrial surface area were smaller, and the expression of DRP1 and fission 1 was increased in the db/db group 28 days after MIRI. Interestingly, 10 mg/kg Tubastatin A significantly mitigated these effects of MIRI in db/db mice. Hypoxia/reoxygenation in the presence of 25.0-mM D-dextrose augmented HDAC6 activity and increased the expression of DRP1 and FIS1, which were blocked by Tubastatin A.Conclusions:Tubastatin A prevents post-MIRI cardiac remodeling and improves cardiac function by limiting mitochondrial fission in type 2 diabetic mice.