Risultati per: Nuovi farmaci per il danno renale acuto (Acute kidney injury – AKI)

Circulation, Volume 150, Issue Suppl_1, Page A4146297-A4146297, November 12, 2024. Background:The Kidney Failure Risk Equation (KFRE) is an established calculator to predict the risk of kidney failure among patients with chronic kidney disease (CKD). Patients with CKD are more likely to die from cardiovascular (CV) causes than from renal causes, and more likely to experience a non-fatal CV event than to progress to kidney failure. The CV predictive ability of the KFRE among patients with CKD is unclear.Methods:We investigated the association of the 8-variable (age, sex, urine albumin-creatinine ratio [UACR], estimated glomerular filtration rate [eGFR], serum albumin, serum phosphate, serum bicarbonate, serum calcium) 5-year KFRE with CV disease (CVD) and death among 3,034 patients with CKD (eGFR 15-60 mL/min/1.73m2) in the Chronic Renal Insufficiency Cohort (CRIC). KFRE was modeled continuously and by quartiles. CVD was defined as the composite of heart failure hospitalization, myocardial infarction, or stroke. All-cause mortality was a key secondary endpoint.Results:Mean eGFR was 39 ±11 mL/min/1.73m2; median UACR was 89 mg/g [25-75th percentile 13, 619]. Median KFRE 5-year score was 0.7% [25-75th percentile 0.2, 2.9]. Five-year event rates for the primary endpoint for the lowest to highest quartiles of KFRE were 11.6%, 17.7%, 25%, and 31% (P

Circulation, Volume 150, Issue Suppl_1, Page A4142841-A4142841, November 12, 2024. Background:Emerging data reveal the importance of metabolomics in identifying specific amino acids and their metabolites as markers of hypercoagulability and stroke. Hypercoagulability, measured by a global hemostasis assay, is associated with thrombotic risk in patients with acute ischemic stroke (AIS).Hypothesis:AIS Patients undergoing coronary intervention compared to healthy controls (HC) exhibit dysregulated amino acid metabolomics that is associated with coagulation.Methods:Serum samples were collected from HC and AIS patients during the intervention. Untargeted metabolomics was performed using a Thermo-Scientific Q Exactive Plus Orbitrap mass spectrometer with Vanquish Horizon Binary UPLC. Metabolomics results were normalized relative to control subjects and compared to patients with AIS. Whole blood samples were used for the TEG assay, and the results were compared between patients with AIS and HC. Hypercoagulability was defined as platelet-fibrin clot strength (P-FCS) >66.5 mm.Results:AIS patients undergoing interventional procedures (n=12) and HC (n=17) were included. Among AIS patients, 50% were black, 67% were male, and 67% were obese. AIS patients vs. controls had elevated levels of P-FCS (67±3mm vs. 62±2mm) and a higher prevalence of hypercoagulability (83% vs. 0%) (p

Circulation, Volume 150, Issue Suppl_1, Page A4146486-A4146486, November 12, 2024. Introduction:Recent studies using cross-sectional survey data have suggested high prevalence of cardiovascular-metabolic-kidney syndrome in the United States. However, these studies are limited by their cross-sectional design and cannot estimate progression or incidence reliably. In this study, we use the longitudinal nature of the AllofUs cohort to estimate the incidence and observe the progression and impact of CKM syndrome stages within a diverse cohort.Research Aims:To understand the distribution and impact of various stages of CKM syndrome within a diverse population cohort over an extended period and identify risk factors for CKM progression.Methods/Approach:Utilizing data from the AllofUs Research platform, we conducted a longitudinal analysis of patients within the cohort. Prevalence was calculated annually, while incidence was estimated by identifying new diagnoses of CKM syndrome. The incidence rate was calculated as the number of new diagnoses over the number of people at risk of developing that stage, using a one-year look-back window. We defined CKM stages according to recent AHA criteria, and additionally created three additional stages, which we termed Stage 5 (CVD and CKD stage 3-5), Stage 6 ( >=2 CVD and CKD stage 3-5), and Stage 7 CKM ( >=2 CVD, CKD stage 3-5, and >= one metabolic risk factor).Results:Our analysis revealed that the prevalence of CKM syndrome increased over the study period. For instance, the prevalence of Stage 1 CKM syndrome increased from 64.7% in 2018 to 80.18% in 2021, while Stage 2 CKM syndrome rose from 84.5% in 2018 to 92.91% in 2021. The incidence of various CKM stages in 2021 are shown in Table 1. The prevalence of all CKM stages are shown in Figure 1. At the conference, we will present models of risk factors for progression of CKM over time.Conclusions:More than 9 in 10 participants in a large nationwide cohort had Stage 2 CKM and the annual incidence of CKM ranged from 12% for Stage 1 CKM to ~3% for stage 4 CKM.

Circulation, Volume 150, Issue Suppl_1, Page A4135869-A4135869, November 12, 2024. Background:Pulsed field ablation (PFA) has emerged as an innovative technology for treating cardiac arrhythmias. PFA increases cell permeability, which can lead to apoptosis. Greater PFA energy may be necessary to ablate ventricular myocardium for ventricular tachycardia circuits, but this carries risks of side effects such as gaseous formation (microbubbles) and hemolysis. Ethanol (EtOH) infusion has been used to ablate pathologic myocardial tissues in hypertrophic cardiomyopathy and for refractory arrhythmias.Hypothesis:We hypothesize that PFA in the ventricle can increase EtOH uptake through PFA-generated pores, thereby enhancing ablation efficacy, even at low powers, by utilizing the cell permeability effects of PFA.Aim:The aim of this study is to investigate the effect of local EtOH infusion after PFA on lesion size in porcine ventricles.Methods:The ventricles of five porcine subjects were ablatedin vivowith a PFA low power setting (750 V, at 20 μs for 50 pulses separated by 200 ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). After PFA was performed, 2 ml of 90 % EtOH vs. saline (control) was infused through the catheter tip to the site of ablation. We compared the electrograms voltage amplitude reduction before and after PFA, and the ablation lesion characteristics.Results:A total of 10 lesions in the control group and 9 lesions in the EtOH group were analyzed. For the controls, the voltage after PFA was not reduced. In contrast, for the EtOH group, the voltage after PFA was significantly reduced (Figure 1A). On gross pathology, there were significant differences in ablation lesion depths and volumes between the 2 lesion sets (Figure 1A-B).Conclusion:Local EtOH infusion after ventricular PFA enhanced acute efficacy of electroporation. Concurrent PFA with local EtOH infusion has the potential to improve efficacy without requiring higher energy parameters, thereby reducing PFA risks. Future studies on chronic efficacy are warranted.

Circulation, Volume 150, Issue Suppl_1, Page A4145225-A4145225, November 12, 2024. Background:Sodium-glucose co-transporter two inhibitors (SGLT2i) have recently been included in heart failure (HF) guidelines due to their benefits in reducing mortality and hospitalization rates. However, the benefits of SGLT2i in patients with post-acute myocardial infarction (MI) remain controversial. Therefore, we aim to perform an updated systematic review and meta-analysis comparing SGLT2i with placebo in patients after an acute MI.Methods:We performed a systematic review and meta-analysis to determine the impact of SLGT2i in patients with post-acute MI with or without diabetes type II (DM II). We systematically searched Pubmed, Cochrane, and Embase for randomized controlled trials (RCTs) comparing SGLT2i and placebo in patients following an acute MI. The primary outcome assessed was (1) HF hospitalization. In this analysis, we also included the following secondary outcomes:(2) cardiovascular (CV) mortality and (3) MI recurrence. Risk Ratios(RRs) with 95% confidence interval (CI) were pooled across studies using a random effect model.Results:Our meta-analysis included ten RCTs comprising 25908 patients, of whom 14098 (54.4%) received SGLT2i therapy and 15078 (58.2%) had type II diabetes. The mean age was 62 years, and the mean follow-up was 21.2 months. In the pooled analysis, HF hospitalization was significantly lower in the SGLT2is group (RR 0.76; 95%CI 0.68,0.84; p

Circulation, Volume 150, Issue Suppl_1, Page A4141513-A4141513, November 12, 2024. Background:The beneficial effect of SGLT-2 inhibitors in managing type 2 diabetes mellitus and heart failure with reduced ejection fraction has already been established. However, the outcomes of dapagliflozin on cardiovascular events in patients with acute myocardial infarction are not well studied.Hypothesis:Our study aims to investigate the effect of dapagliflozin in reducing cardiovascular events among patients with acute myocardial infarction.Methods:A systematic search was conducted using multiple electronic databases from inception until March 2024 using the appropriate Mesh terms, “ dapagliflozin,” “SGLT 2 inhibitors,” “acute myocardial infarction,” “heart failure,” “major cardiovascular events,” “all-cause mortality.” We used the random effect model to calculate the pooled relative risk and their corresponding confidence interval. A p-value of

Circulation, Volume 150, Issue Suppl_1, Page A4113561-A4113561, November 12, 2024. Background:Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated mortality benefits in patients with heart failure (HF). Since acute coronary syndrome (ACS) is an increasingly prevalent cardiovascular condition that often leads to HF, SGLT2i might play a role in reducing mortality in these patients. Previous randomized controlled trials (RCTs) have demonstrated inconsistent efficacy of Empagliflozin, an SGLT2i, in patients with ACS.Methods:A comprehensive systematic literature search was conducted spanning the major bibliographic databases to retrieve RCTs comparing Empagliflozin to placebo in patients with ACS. Odds ratios (OR) and mean differences (MD) with 95% confidence intervals were pooled using the DerSimonian and Laird random-effects model with statistical significance set at p

Circulation, Volume 150, Issue Suppl_1, Page A4140939-A4140939, November 12, 2024. Background:In-hospital mortality from acute ischemic stroke (AIS) remains a major concern in developing countries where access to thrombectomy or fibrinolytics is limited. Platelet-to-lymphocyte ratio (PLR) has been suggested as an inflammatory marker associated with poor outcomes in AIS. Therefore, we aim to evaluate the value of PLR as a predictor of in-hospital mortality in first-ever AIS.Methods:We evaluated the records of 293 patients with a first-ever AIS from a third-level hospital in Ecuador from 2016-2022. Immunocompromised patients, those who had active infections, autoimmune diseases, or malignancies were excluded. The PLR was calculated by dividing platelet by lymphocyte count. Participants were classified into low or high PLR groups based on the median. Univariate and multivariate logistic analyses were used to determine predictors of in-hospital mortality. A ROC curve analysis was performed to identify the optimal cutoff value of PLR for predicting the outcome.Results:140 patients were eligible for the study. Most patients were male (67.1%) and the median age was 63 years. The median length of hospitalization was 11 days (6-19), and 35% of patients required ICU admission. In-hospital mortality was 20%. Deceased patients were significantly older and had higher rates of ICU admission and NIHSS than survivors. A high PLR was associated with an increased risk of in-hospital mortality (OR =8.30; p= 0.001) in the univariate model. After adjusting for potential confounders, only high PLR (OR =6.02; p= 0.022), ICU admission, and NIHSS remained statistically significant. The ROC curve showed that the optimal cutoff value of PLR for predicting in-hospital mortality was 159.44, with an AUC of 0.799 (Sensitivity: 85.7%, Specificity:77.7%).Conclusion:Our results suggest that PLR is an independent predictor for in-hospital mortality in patients with a first-ever AIS. This biomarker could be useful in developing countries where stroke mortality is still high.

Circulation, Volume 150, Issue Suppl_1, Page A4139467-A4139467, November 12, 2024. Introduction:Acute coronary syndrome (ACS) has been generally considered a relative contraindication to coronary atherectomy.Aims:The objective of this study was to investigate the temporal trends and hospital variability in the use of coronary atherectomy and its outcomes among patients undergoing percutaneous coronary intervention (PCI) for ACS from a nationwide PCI registry in Japan.Methods:First, we analyzed the temporal trend in the use of rotational atherectomy (RA) and orbital atherectomy (OA) during PCI for ACS patients between 2014 and 2022 (822,237 PCIs from 1,269 hospitals). Next, we assessed the outcomes of the patients who underwent RA for ACS between 2019 and 2022 (7,421 patients across 662 hospitals). The primary outcome was in-hospital mortality after PCI. Patient outcomes associated with hospital PCI volumes and the device policy change on coronary atherectomy in Japan in 2020, which allowed operators to perform coronary atherectomy without on-site surgical backup, were also evaluated.Results:The rate of RA for ACS was low at 2.0% in the overall cohort (16,264/822,237 PCIs); the rate slightly increased from 1.9% in 2014-2019 to 2.1% in 2020-2022 (after the device policy change). The rate of PCI with OA for ACS was also low at 0.8% in 2021-2022 (1,404/185,141 PCIs). Increasing the complexity of baseline characteristics, including advanced age, diabetes, chronic kidney disease, dialysis, peripheral arterial disease, prior coronary artery bypass grafting, ST-segment elevation myocardial infarction, cardiac arrest within 24 h, cardiogenic shock within 24 h, three-vessel disease, and mechanical circulatory support during PCI was significantly associated with increased in-hospital mortality after PCI with RA in ACS patients (P

Circulation, Volume 150, Issue Suppl_1, Page A4145406-A4145406, November 12, 2024. Background:Atrial fibrillation (AF) is the most common arrhythmia. Patients with AF are at high risk of pulmonary embolism (PE). Similarly, patients with PE are at high risk of AF. There is scarcity of data regarding the outcomes of acute pulmonary embolism in the patients with preexisting AF.Methods:This is an analysis of the National Inpatient Sample of the years 2016 to 2020. We identified patients who were admitted with PE using ICD-10-CM codes. We divided the population into two groups by secondary diagnosis of AF. The risk of mortality and in-hospital complications in the PE/AF group was compared to the PE/non-AF group using multivariate logistic regression analysis.Results:During 2016-2020, there were a total of 934225 patients who were admitted with PE, of which 102705(11%) patients had AF. After adjusting for demographics, hospitalized PE patients with AF had higher odds of mortality (aOR (adjusted odds ratio) 1.40; 95% CI 1.30–1.52 p < 0.001), GI bleed (aOR 1.30; 95% CI 1.18–1.43p < 0.001), cardiogenic shock (aOR 1.83; 95% CI 1.64 – 2.04 p< 0.001), cardiac tamponade (aOR 2.93; 95% CI 1.88–4.57 p

Circulation, Volume 150, Issue Suppl_1, Page A4146439-A4146439, November 12, 2024. Background:Progression along Cardiovascular-Kidney-Metabolic (CKM) stages confers greater cardiovascular disease (CVD) risk. However, the factors associated with CKM stage progression over time are not yet defined.Methods:We evaluated ARIC Visit 4 (1996-98) participants without CVD at Visit 1 (1987-89) and with available data to define CKM stages at both Visits 1 and 4. CKM stages were defined as: stage 0, no CKM risk factors; stage 1, excess/dysfunctional adiposity; stage 2, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, or diabetes) and/or moderate- to high-risk chronic kidney disease (CKD); stage 3, ≥20% predicted CVD risk per the PREVENT calculator or very high-risk CKD; and stage 4, clinical CVD. Among those in CKM stages 0-3 at Visit 1, we used logistic regression to concurrently assess the association of age, sex, race, area deprivation index (ADI, a measure of neighborhood deprivation), education, household income, physical activity (categorized as consistently ideal, intermediate, or consistently poor per AHA recommendations), and diet (per Life’s Essential 8 healthy diet score) with progression to a higher CKM stage from Visit 1 to Visit 4.Results:Among 8,376 participants, the mean age at Visit 1 was 55 years, with 52% female and 21% Black adults. Older individuals had higher odds of CKM progression (OR: 1.49 [95% CI 1.42-1.56] per 5-years of age), whereas females had lower odds (OR: 0.72 [0.64-0.80]) and Black race did not have an independent association (Figure). More adverse social determinants of health were associated with higher odds of CKM progression, including higher ADI (deciles 7-10 vs deciles 1-3 OR: 1.39 [1.23-1.57]), lower income (

Circulation, Volume 150, Issue Suppl_1, Page A4143634-A4143634, November 12, 2024. Background:Cardiac microvascular dysfunction is a contributing factor to cardiac ischemia/reperfusion (I/R) injury. The impact of mammalian Ste20-like kinase 4 (MST4) on cardiac microvascular I/R injury remains unknown.Aims:To decipher the role of MST4 in cardiac microvascular I/R injury and the underlying mechanisms.Methods:Single-cell RNA sequencing was performed to explore the expression changes of MST4 in different cardiac cell types. Myeloid-specific MST4 knockout mice (MST4 CKO) and bone marrow transplantation were used to testify to the role of myeloid-derived MST4 in cardiac microvascular I/R injury. Bone-marrow-derived macrophage (BMDM) and cardiac microvascular endothelial cells (CMEC) were used to dissect molecular mechanisms. Adeno-associated virus and adenovirus were constructed to overexpress ATP Citrate Lyase (ACLY) with mutation of serine 455 (S455A) in vivo and in vitro, respectively.Results:MST4 was dominantly upregulated in CCR2+ monocyte-derived macrophages. Myeloid-specific deficiency of MST4 or wild type mice that were transplanted with BMDM from MST4 CKO mice improves cardiac performance in the I/R mouse model. Metabolomics showed that the primary bile acid biosynthesis pathway was upregulated in BMDM overexpressing MST4. The level of 7α-hydroxyl3-oxo-4-cholestenoic acid (7-HOCA), an intermediate of bile acid, was dramatically increased in I/R mice or BMDM overexpressing MST4, which can be reversed by knocking down MST4. Phosphoproteomics and LC-MS/MS analysis discovered that ACLY was one of the most important substrates of MST4 in the process of I/R injury. ACLY was directly phosphorylated by MST4 at serine 455, which increased ACLY enzyme activity. Mechanistically, ACLY promoted cholesterol catabolism through the bile acid synthesis pathway, leading to the accumulation of 7-HOCA in the macrophage-endothelial cell microenvironment. A high level of 7-HOCA was able to promote endothelial cell mtDNA release, leading to endothelial cell pyroptosis through the inflammasome pathway. However, mutation of serine 455 of ACLY blocked the role of MST4.Conclusions:Our data defined a previously unrecognized role of the MST4/ACLY pathway in cardiac microvascular I/R injury. MST4 led to the accumulation of 7-HOCA by phosphorylating ACLY, furthermore, 7-HOCA promoted endothelial cell injury. Targeting the MST4/ACLY pathway ameliorated cardiac microvascular I/R injury, which may provide a novel therapeutic strategy for I/R injury.

Circulation, Volume 150, Issue Suppl_1, Page A4146430-A4146430, November 12, 2024. Background:Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). Excess sympathetic nerve activity (SNA) is thought to be a major mechanism for elevated cardiovascular risk in these patients. However, the mechanisms that drive excess SNA in patients with CKD are not well understood. A growing body of evidence suggests that CKD is associated with inflammation and immune dysfunction. However, the role of neuroinflammation in CKD has not been studied.Hypothesis:We hypothesize that microglial activation and neuroinflammation underlies excess sympathetic activity in chronic kidney disease (CKD).Aim:Understand the extent to which microglia mediate neuroinflammation and contribute to excess SNA in CKD.Methods:C57/BL6 mice (18-22 gm, 8 weeks old) were randomized to 0.2% adenine in casein (CKD) or continued on casein-only diet (Control) for 2, 4 or 6 weeks. SNA was assessed by heart rate variability, as determined by spectral analysis of the electrocardiogram (Low Frequency / High-Frequency HF/LF ratio) and catecholamine levels (ELISA). Neuroinflammation will be evaluated by profiling the cytokines/chemokines in serum and CSF using Luminex cytokine array. Microglia phenotyping was performed by flow cytometry. Renal function was quantified by serum creatinine and cystatin C levels.Results:The adenine model resulted in significant CKD by 2 weeks. SNA was increased by week 4 as evidenced by an increased LF/HF ratio [0.46 ± 0.1 in CKD vs. 0.21 ± 0.05 Controls] P = 0.02. There were no differences in SNA at 2 weeks. However, changes in microglia were evident as early as 2 weeks, with CKD mice showing significantly increased numbers of activated microglia (CD11b+ CD45low/int P2RY12+ CD86+) (P = 0.007). The areas of the brain that control sympathetic output showed excess microglia.Conclusion(s):Our data suggests that CKD is associated with neuroinflammation in sympathetic areas of the brain. Microglia activation precedes increases in SNA. Experiments to examine the effect of microglia depletion on SNA are ongoing. Together, these experiments will provide comprehensive insight into how microglial function and neuroinflammation synergize to increase SNA in CKD.

Circulation, Volume 150, Issue Suppl_1, Page A4141052-A4141052, November 12, 2024. Introduction:Cardio-cerebral infarction, a rare clinical presentation involving simultaneous acute ischemic stroke and acute myocardial infarction, poses significant therapeutic challenges. The incidence of this dual infarction is currently unknown due to its rarity. Delaying intervention for one condition to address the other can lead to permanent morbidity, disability, or even death. Coronary artery fistulas are uncommon with estimated incidence of 0.3%. Among these, a fistula between the left anterior descending artery and the pulmonary artery is the rarest variant, comprising about 17% of all coronary artery fistula cases.Case:A 54-year-old male, with a known history of atrial fibrillation and hypertension, presented to our emergency department with non-rotatory dizziness. Physical examination was unremarkable, but neurological examination revealed medial rectus palsy and left facial asymmetry. A cranial MRI indicated a hyperacute infarction in the left cerebellum. Laboratory tests showed markedly elevated troponin I levels ( >50 ng/ml) and atrial fibrillation, along with inferior wall ST elevation on the electrocardiogram. Due to the high risk of hemorrhagic conversion, the loading of antiplatelets was deferred. Instead, the patient was treated with Aspirin 80 mg once daily, Clopidogrel 75 mg once daily, and Enoxaparin 0.4 ml subcutaneously once daily. A 2D echocardiogram revealed an ejection fraction of 43%, hypokinesia of the anterior and intraventricular septum from base to apex, and severe mitral stenosis. Cardiac catheterization identified a coronary artery fistula from the left anterior descending coronary artery to the main pulmonary artery. Treatment for acute coronary syndrome and acute cerebellar infarct continued. An open-heart surgery was considered. However, during his hospital stay, the patient experienced hemorrhagic conversion and altered sensorium. His condition further deteriorated, necessitating a tracheostomy and long-term care.Conclusion:Cardio-cerebral infarction is an extremely rare and poorly studied syndrome that presents significant treatment challenges and carries a grave prognosis if not addressed immediately. The medical conundrum of deciding which condition to treat first underscores the need for further research. Both interventional cardiologists and interventional neuroradiologists play crucial roles in the effective management of this emergency condition.

Circulation, Volume 150, Issue Suppl_1, Page A4124277-A4124277, November 12, 2024. Background:Ischemic heart disease remains the leading cause of death worldwide. Early coronary revascularization is the most important treatment. Recent findings have revealed that reactive oxygen species (ROS) can lead to tissue damage following coronary artery revascularization, known as ischemia-reperfusion injury. In this study, we focused on a novel free radical scavenger, resorcimoline (RML). Last year, we reported the scavenging activity of RMLin vitroagainst multiple ROS, confirmed by the electron spin resonance spectrometry.Hypothesis:Resorcimoline might reduce ROS damage in cardiomyocytes, thereby exerting cardioprotective effects following coronary ischemia-reperfusion injury.Methods:Nine-to-eleven-week-old male Wistar rats were subjected to acute myocardial ischemia induced by ligation of the left anterior descending coronary artery for 30 minutes. Rats received intravenous injections of RML at 6 mg/kg before the ligation release or saline as a control. The heart sections were double-stained at 24-hour reperfusion with Evans blue and triphenyltetrazolium chloride to assess the infarct area. Cardiac function was evaluated at 2-day and 7-day reperfusion with echocardiography. Myocardial fibrosis was assessed at 7-day reperfusion by Masson’s trichrome staining. Primary cultured rat cardiomyocytes were treated with 10 μM angiotensin II for 3.5 hours and then exposed to RML for 30 minutes. Cellular ROS assay kits were used to assess the levels of ROS in the cardiomyocytes.Results:Infarct size in RML-treated animals was significantly smaller than in control animals (41.8±19.4% vs. 60.8±12.9%, p=0.03, Fig. 1A). Apoptotic cells in the border zone were significantly reduced in RML-treated animals (32.0±11.7% vs. 55.1±16.9%, p=0.01, Fig. 1B). Troponin I level in RML-treated animals was significantly lower than in control animals (p=0.04, Fig. 1C). Ejection fraction in RML-treated animals was significantly preserved at 2-day reperfusion and 7-day reperfusion when compared to control animals (p=0.001, p=0.003, Fig. 2A). Myocardial fibrosis area in RML-treated animals was significantly smaller than in control animals (23.9±11.7% vs. 40.6±15.6%, p=0.01, Fig. 2B). RML significantly reduced angiotensin II-induced ROS in cardiomyocytes in a concentration-dependent manner (Fig. 3A,B,C).Conclusion:Resorcimoline exhibits cardioprotective effects following coronary ischemia-reperfusion injury by reducing the infarct size and ROS damage in cardiomyocytes.

Circulation, Volume 150, Issue Suppl_1, Page A4144742-A4144742, November 12, 2024. Introduction:Although Frozen Elephant Trunk has emerged as a valuable technique in aortic arch pathology it is still burdened by a high mortality and morbidity rate due to the technical complexity and clinical and anatomical substrates.Research Questions:Evaluation of early hard outcomes in a surgical approach encompassing the following : 1) central cannulation of the right subclavian artery or the right axillary artery; 2) debranch-first approach (selective cannulation of left common carotid artery with single 8-mm dacron graft and the left subclavian artery for cerebral perfusion with single 10-mm dacron graft); 3) central venous cannulation of right atrium; 4) use of a home-made 4-branched perfusion circuit for extracorporeal circulation; 5) brachiocephalic artery clamping at 26–28°C and beginning of selective antegrade perfusion. The aortic arch is opened and the distal stent graft of the hybrid prosthesis is released into the descending thoracic aorta. The strengthened collar of the prosthesis is sutured to the aorta, and, after cannulation of the fourth lateral branch, systemic perfusion is resumed. The anastomosis between the hybrid prosthesis and sino-tubular junction is then completed and the cross-clamp is released. The prosthesis-elongated supra-aortic vessels are then termino-terminally re-anastomosed to the corresponding branches of the hybrid prosthesis.Methods:Retrospective analysis of a prospectively collected database including 167 patients referred for FET (55 %acute aortic dissections, 14.5% chronic aortic dissections, and 30.5% extended aneurysms, 67% males, 9.2% diabetes mellitus, 72% arterial hypertension, 8.2% chronic renal failure, 12% peripheral vasculopathy, 3% bicuspid aortic valve, 11.9% redo)Results:The average cardio-pulmonary bypass time, crossclamp time, cerebral and visceral perfusion time is 192, 102, 29 and 12 minutes, respectively. In-hospital mortality occurred in 16% (44% due to respiratory failure), spinal cord injury in 2.8% and stroke in 3.5% of patients.Conclusion:Debranch-first technique and cerebral protection through the trivascular perfusion strategy appear safe and effective in the treatment of complex arch pathology.