Risultati per: Prevenzione e trattamento della sindrome post-trombotica

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.

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 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 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 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 A4141509-A4141509, November 12, 2024. Background:Dietary stearic acid (18:0), a saturated fatty acid (SFA) commonly present in Western diets, has an LDL-C lowering effect compared to shorter chain SFAs such as palmitic acid (16:0), and a similar effect compared to oleic acid (18:1). However, the underlying mechanisms remain unclear.Hypothesis:We tested the hypothesis that the hypocholesterolemic effect of dietary 18:0 and 18:1 relative to 16:0 is modulated by alterations in cholesterol and bile acid (BA) metabolism.Methods:This secondary analysis used archived plasma and fecal samples from a randomized crossover feeding study (N=20 mildly hypercholesteremic postmenopausal women, 64±7 years, BMI 26.4±3.4kg/m2). Participants consumed each of 3 isocaloric diets enriched in either 18:0, 16:0 or 18:1 for five weeks with a 2-week washout. Primary (P) and secondary (S) BAs, and their conjugates were measured in fecal, fasting and non-fasting (NF) plasma samples using the Biocrates MxP Quant 500 kit and Quadrupole Time-of-Flight mass spectrometry. Fasting and NF plasma cholesterol synthesis (lathosterol) and absorption (-sitosterol) markerswere quantified using gas chromatography. Mixed-effect and generalized linear mixed models were used to test the difference in outcome measures among diets, with Tukey-Kramer post hoc comparison. Spearman correlation coefficients with FDR adjustment was calculated between BA, cholesterol synthesis/absorption markers, and CVD risk factors.Results:Compared to the 16:0 diet, consumption of the 18:0 diet resulted in significantly lower fasting and NF plasma lathosterol (-22%); higher -sitosterol (19%); higher fecal PBAs (31%) and lower fecal SBAs (-17%) concentrations. Plasma PBAs were significantly lower in the fasted state (-34%), but higher in the NF state (21%; 18:0 vs. 16:0). Interestingly, conjugated PBA and SBA concentrations in the NF state were significantly higher after participants consumed the 18:0 compared to the 18:1 diet (all p

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 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

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.

Circulation, Volume 150, Issue Suppl_1, Page A4145775-A4145775, November 12, 2024. Background:Cyclophosphamide is an alkylating agent of the nitrogen mustard class that has become standard of care for graft-versus-host disease prophylaxis after hematopoietic stem cell transplantation. Although its cardiac toxicity in conditioning regimens is well-documented, data on cardiac events after administration of post-transplant cyclophosphamide (PT-Cy) administration remains limited.Research Question:Is PT-Cy associated with a higher incidence of cardiac adverse events compared with no PT-Cy?Aims:We aimed to perform a systematic review and meta-analysis of cardiac events from studies comparing PT-Cy versus no PT-Cy in patients with hematological disorders who received hematopoietic stem cell transplantation.Methods:We searched PubMed, Embase, and Cochrane Library for studies comparing PT-Cy versus no PT-Cy in patients with hematological conditions who received hematopoietic stem cell transplantation. We pooled risk ratios (RR) with 95% confidence intervals (CI). Statistical analyses were performed using Review Manager 5.4.1, under a random-effects model. Heterogeneity was assessed using I2 statistics.Results:We included four studies, all of which were retrospective, with 1,546 patients, of whom 826 (53%) received PT-Cy. Age ranged from 18 to 77 years, and 840 (54%) were male. A total of 1549 allogeneic transplants were performed, primarily for malignant hematological conditions. The conditioning regimens used were myeloablative (52%), reduced intensity (33%), non-myeloablative (8%), and sequential (7%). The most common cardiac events in patients receiving PT-Cy were heart failure (28%) and cardiomyopathy (27%), followed by arrhythmias (25%), pericarditis/pericardial effusion (14%) and acute coronary syndrome (5%). The incidence of adverse cardiac events was significantly higher in patients who received PT-Cy compared with those who did not receive PT-Cy (RR 2.05; 95% CI 1.36, 3.10; p

Circulation, Volume 150, Issue Suppl_1, Page ASu907-ASu907, November 12, 2024. Background:Abnormal potassium levels are common findings in the intensive care unit (ICU) population. We aimed to determine the incidence of dyskalemias at ICU admission and their association with functional outcome in comatose patients resuscitated from cardiac arrest.Hypothesis:We hypothesized that both hypokalemia and hyperkalemia are associated with unfavorable functional outcome.Methods:Pooled data from four randomized clinical trials in comatose post-cardiac arrest patients admitted to ICU after return of spontaneous circulation (ROSC). Reference potassium levels were defined as between 3 and 4.9 mmol/L, as proposed in the Simplified Acute Physiology Score II. Favorable functional outcome was defined as a Cerebral Performance Category of 1 or 2 at 180 days.Results:We included 1133 patients (557 from HYPERION, 346 from TTH48, 120 from COMACARE and 110 from Xe-HYPOTHECA) with a median age of 64 (IQR: 55-72) years and a predominance of males (72%). Overall, 421 (36%) patients had favorable functional outcome. On admission, 221 (19.5%) patients experienced hyperkalemia and 35 (3.1%) patients experienced hypokalemia. More patients in the normokalemia group (364/877, 41.5%) had a favorable functional outcome, as compared to the hypokalemia (11/35, 31.4%) and hyperkalemia (41/221, 18.6%) groups p

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.

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 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 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.