Search Results for: Nelle donne lo stress danneggia la salute dell’intestino

Circulation, Volume 150, Issue Suppl_1, Page A4143788-A4143788, November 12, 2024. Background:Physical activity (PA) reduces cardiovascular (CV) disease risk, and this has recently been shown to be due, in part, to reduction of stress-related neural activity (SNA). Further, the CV benefits of PA are higher in individuals likely to have higher baseline SNA (i.e., those with depression/anxiety). Moreover, anxiety and depression associate with increased risk of deep venous thrombosis (DVT) partly through increased SNA, yet it remains unknown how PA impacts this relationship.Hypotheses:1) PA associates with lower risk of DVT, 2) this PA benefit is more pronounced in individuals with anxiety and depression.Aims:To evaluate the association between PA and DVT risk and the differential benefits among subjects with anxiety or depression.Methods:Subjects enrolled in the Mass General Brigham Biobank were studied; total PA was derived from a health survey that assessed different activities during the previous year. Highervslower PA was defined according to quintiles of PA in our population (low PA: 1° and 2° quintile; high PA: 4° and 5° quintile; subjects in the 3° quintile were excluded to avoid possible overlaps). Depression, anxiety, and DVT were defined using ICD codes. Subjects

Circulation, Volume 150, Issue Suppl_1, Page A4144270-A4144270, November 12, 2024. Background:Air pollution is a leading cause of cardiovascular diseases including ischemic heart disease and stroke contributing to millions of deaths, with elevated blood pressure, endothelial dysfunction, and systemic inflammation being some of the most important underlying mechanisms. Various studies showed a promising beneficial effect of indoor air purification on various health outcomes, including blood pressure. We aimed to assess the effect of indoor air purification on systolic blood pressure (SBP) and Diastolic blood pressure (DBP) and provide a rationale for home use of these filters.Methods:We searched PubMed, Web of Science, Cochrane and Scopus for published literature up to May 2024. We included studies that assessed air purification, including HEPA filters or electrostatic air filters, as an intervention compared to no intervention. The primary outcome of interest was mean changes in blood pressure both systolic and diastolic. Secondary outcomes were biomarkers of inflammation and oxidative stress. Mean difference (MD) and 95% CI was used in a fixed-effect model to analyze the data.Results:A total of 21 studies were included in our meta-analysis with a total of 1955 participants. Air purification was associated with a significant reduction in systolic blood pressure (SBP) (MD: -2.42, 95% CI: -3.42, -1.41), and diastolic blood pressure (DBP) (MD: -1.11, 95% CI: -1.76, -0.46). However, there was no significant changes in levels of inflammatory biomarkers or oxidative stress.Conclusion: Indoor air purification was associated with significant reductions in systolic and diastolic blood pressure levels, but questions arise whether these reductions are clinically relevant or not. Further studies should assess these findings.Conclusion:Indoor air purification was associated with significant reductions in systolic and diastolic blood pressure levels, but questions arise whether these reductions are clinically relevant or not. Further studies should assess these findings.

Circulation, Volume 150, Issue Suppl_1, Page A4146892-A4146892, November 12, 2024. Background:Takotsubo cardiomyopathy (TCM) is a unique and reversible heart condition typically triggered by intense emotional or physical stress. Meanwhile, Cirrhosis, a chronic liver disease, is associated with increasing inflammation and oxidative stress, which can potentially worsen cardiovascular problems. In this study, we aimed to study the impact of cirrhosis on outcomes in TCM.Methods:A retrospective analysis was performed using the NIS database 2016 -2020 and the International Classification of Diseases, Tenth Revision codes to identify patients > 18 years old with the principal diagnosis of Takotsubo cardiomyopathy. The effect of cirrhosis was studied on in-hospital mortality and secondary outcomes such as cardiogenic shock, ventricular arrhythmia (VA), acute respiratory and acute kidney injury (AKI), as well as resource utilisation. Categorical variables were compared using the chi-square test, and continuous variables were compared using the t-test—multivariable regression analyses adjusted for demographics, hospital-level characteristics, and relevant comorbidities.Results:We identified a total of 190,025 patients with TCM. Of these, 3,335 (1.76%) patients had liver cirrhosis, with notably higher prevalence of diabetes (33.6%), CKD (20.7%), anemia (10.2%), and major depressive disorder (25.6%) in the cirrhosis group. A higher incidence of in-hospital mortality (12.9% vs. 6.3%, p

Circulation, Volume 150, Issue Suppl_1, Page A4143515-A4143515, November 12, 2024. Background:There is growing interest in understanding microbubble (MB) behavior under ultrasound (US) in complexin vivoenvironments, to optimize safety and efficacy for various clinical applications,e.g., large molecule drug delivery, temporary blood-brain-barrier opening, and thrombus disintegration. However, there have been few mechanisticin vivostudies due to the challenges of visualizing vibrating MBs in the circulation at high temporal resolutions. Our study elucidates MB interactions with surrounding microvessels using ultra-fast intravital imaging of the rat cremaster muscle.Hypothesis:MB vibration-induced stress deforms surrounding microvesselsin vivo.Deformations are influenced by not only the US parameters, but also the biomechanical properties of the vessel wall.Methods:Definity® was injected via the femoral artery of anesthetized rats and imaged in externalized cremaster muscle using an ultrafast microscope (up to 12 Mfps). Concurrently, a single US pulse of 6-10 cycles [1 MHz, peak negative pressures (PNP) 0.5-2.0 MPa] was delivered. Images were analyzed to calculate MB and vessel dimensions and to perform Fourier analyses. Stress-strain curves were generated using normal stress exerted by the MB (derived from the linearized Euler’s equation) and measured circumferential vessel strain (Diameter/initial Diameter-1).Results:MBs expanded in both circular and elliptical shapes (Fig 1A), and vibrated nonlinearly under US. Vessels vibrated in-phase with the MBs at higher PNP (Fig 1B). Fourier analyses revealed nonlinear vessel vibration (Fig 1C) at fundamental and harmonic US frequencies. Calculated normal stress exerted by the MB of three MB-vessel pairs displayed linear relationships with measured circumferential vessel strain (Fig 1D), with slopes (representing Young’s modulus, or stiffness) between 0.6-1.7 MPa.Conclusions:We demonstrate, for the first time, microvascular harmonic behavior in response to MB vibration under US; the associated bioeffects warrant further investigation. Finally, we introduce a novel method for measuringin vivomicrovessel stiffness using MBs as mechanical probes, where vessel stiffness is represented by the slope of the presented stress-strain curve.

Circulation, Volume 150, Issue Suppl_1, Page A4143092-A4143092, November 12, 2024. Background:Very high level, lifelong aerobic exercise results in lower ventricular stiffness and left ventricular wall stress (LVWS) LVWS is an important predictor of future heart failure risk. To what degree LVWS changes with various doses of lifelong aerobic exercise is unknown.Objective:The purpose of this study was to determine the impact of lifelong exercise on LVWS.Methods:Seniors (n = 58) who consistently participated in lifelong patterns of exercise training were recruited and categorized into 3 groups: “sedentary” (

Circulation, Volume 150, Issue Suppl_1, Page A4144377-A4144377, November 12, 2024. Mammalian cells have several adaptive mechanisms to counteract the adverse effects of metabolic and redox stress induced by ischemia. Hypoxia, a hallmark of ischemia, results in the selective reduction of the tricarboxylic acid cycle metabolite, α-ketoglutarate, to theL-(S)-enantiomer of 2-hydroxyglutarate (L2HG) in several cell types. L2HG protects hypoxic cells by buffering increases in the NADH/NAD+redox couple and inhibiting mitochondrial electron transport. In addition, the accumulation of L2HG induced by genetic knockout of L2HG dehydrogenase (L2HGDH), the only known enzyme capable of oxidizing L2HG back to α-ketoglutarate, protects mice against myocardial injury during ischemia. This protection by L2HG manifests as decreased myocardial infarct size and improved cardiac function, owing partly to a metabolic shift in carbon flux from glycolysis towards the pentose phosphate pathway. However, myocardial ischemia also leads to perturbations in fatty acid metabolism as manifest by accumulation of acylcarnitines and acyl-CoA’s. It remains unclear as to whether or not L2HG accumulation affects fatty acid metabolic homeostasis during myocardial ischemia. Here, we induced L2HG accumulation by homozygous deletion of thel2hgdhgene in male mice (l2hgdh-/-; n=12). Hearts isolated from these mice and their wild-type littermates (l2hgdh+/+; n=13) were subjected toex vivoLangendorff perfusion at coronary perfusion pressure of 80 mmHg for 30 min with (ischemic group) or without (control group) subsequent perfusion at ~10% pressure for 90 min. Using liquid chromatography tandem mass spectrometry (LC-MS/MS)-based nontargeted lipidomics, we identified several species of long chain acylcarnitines that accumulated by ischemia in hearts obtained fromL2HGDH+/+mice [linoleoyl carnitine, palmitoyl carnitine, and hydroxy-linoleoyl carnitine increased by 13.2-fold (p=4.2 x 10-6), 10.7-fold (p=1.7 x 10-6), and 10.0-fold (p=5.8 x 10-6), respectively]. Interestingly, however, this accumulation was attenuated substantially in ischemic hearts obtained fromL2HGDH-/-mice [hydroxy-linoleoyl carnitine, palmitoyl carnitine, and linoleoyl carnitine were downregulated by 62.6% (p=0.034), 54.2% (p=0.018), and 35.4% (p=0.054) in ischemic hearts fromL2HGDH-/-mice when compared toL2HGD+/+littermates]. Overall, these findings highlight a novel and potentially important role for L2HG in restoring the perturbations in fatty acid metabolism induced by myocardial ischemia.

Circulation, Volume 150, Issue Suppl_1, Page A4119210-A4119210, November 12, 2024. Introduction:Insulin growth factor (IGF) binding protein-1 and 2 (IGFBP-1 and 2) are implicated in acute myocardial infarction (AMI) and have been suggested as predictors of mortality and development of heart failure. The IGF axis has been shown to play roles in cell proliferation and apoptosis. We analysed the serum IGFBP-1 and 2 levels in AMI before and after percutaneous coronary intervention (PCI) and correlated this with cardiac magnetic resonance (CMR) imaging to better establish their significance as biomarkers in AMI.Methods:Patients with AMI who presented to Royal Free Hospital, London, were recruited for proteomic analysis (O link Proximity Extension Immunoassay) at presentation, 24h and 72h following primary PCI. All underwent both admission and follow-up CMR at 6 months to assess for myocardial oedema, left ventricular volumes and function, and assessment of scar.Results:Proteomic evaluation in 20 AMI patients (male 95%; median age 59) revealed significant reduction in the average IGFBP-1 values at discharge compared with presentation, from 5.93 to 4.52 (24% reduction, p=0.003). Conversely, the average IGFBP-2 values at discharge significantly increased from 7.66 to 8.29 (8% increase, p=0.001). Higher discharge IGFBP-2 value was also correlated with increased indexed left ventricle end diastolic volume (LVEDV) at 6-month follow-up (R=0.54, p=0.032).Discussion:IGFBP-1 and 2 showed significant change following intervention for AMI. IGFBP-1 is a stress hormone, which is directly and indirectly activated by cytokines, dysglycaemia and vasopressin activation. Its subsequent reduction following PCI in AMI indicates relative resolution of inflammation, but this was not correlated with changes in infarct size or LV function at follow-up. IGFBP-2 showed significant upregulation, and higher values at discharge were significantly correlated with increased LDEDV at follow-up, suggesting adverse clinical outcomes within this setting. This data suggests differential roles of IGFBP-1 and 2 in the pathogenesis of AMI.

Circulation, Volume 150, Issue Suppl_1, Page A4140462-A4140462, November 12, 2024. Background:Right ventricular pacing (RVP) can have adverse cardiac effects and cause pacing induced cardiomyopathy (PiCM). His bundle pacing (HBP)&Left Bundle Branch area pacing (LBBAP) mimic physiologic conduction (PhysioP) and maintain biventricular synchrony.Hypothesis and Aims:Reduced left ventricular (LV) systolic function reserve in the presence of normal baseline LV ejection fraction (EF) could precede development of RV PiCM. Our aim was to compare the effects of RVP vs. PhysioP on bicycle exercise cardiopulmonary performance in patients with normal LVEF who required pacing for bradyarrhythmias.Methods:Patients with sinus rhythm and RVP or PhysioP&ventricular pacing burden of >70% who completed cardiopulmonary exercise test and simultaneous stress echocardiography (SE) were included. Pulmonary gas exchange was calculated using Ventilation/CO2 production at rest and during exercise. Changes in LV size, EF, longitudinal strain and diastolic function and gas exchange parameters were compared post and pre exercise in the 2 groups.Results:25 of 29 patients completed the study [68 ± 23 yrs, 48% M; LVEF 56±5%, 11 RVP, 14 PhysioP]. There was no difference in baseline demographic&clinical variables, exercise duration, rest and peak heart rate and blood pressure between 2 groups. Pacing duration was 2.61±1.48 yrs in RVP vs. 0.84±0.67 yrs (p=0.003) in the Physio group. Resting echocardiographic parameters (Table 1A)were comparable. Compared to RVP, reduction in LV end-diastolic volume (EDV) 3.4±14.1 ml vs. -23.1±18.1ml, p=0.006)&LV end-systolic volume (ESV -5.7±11.6 ml vs. -18.0±9.5ml, p=0.01) was more pronounced in the PhysioP group. Changes in LVEF, LV strain&diastolic function were not different between the 2 groups (Table 1B). There were no significant differences in changes in pulmonary gas exchange parameters in the 2 groups.Conclusions:In patients with normal LVEF and pacemaker dependent, RVP is associated with impaired but PhysioP with preserved LV systolic function reserve, which can be detected by exercise SE. SE may help identify patients at risk for RV PiCM. Benefit of PhysioP needs to be determined by larger studies with longer follow-up.

Circulation, Volume 150, Issue Suppl_1, Page A4117657-A4117657, November 12, 2024. Background:Primary pulmonary arterial hypertension (PAH) is a disease affecting young subjects. It has very poor prognosis and optimal treatment is not available. 15-hydroxyeicosatetraenoic acid (15-HETE), a potent vasoconstrictor, has been implicated in the pathogenesis of PAH. Elevated levels of 15-HETE have been shown to be associated with worse prognosis in patients with PAH. Oral ingestion of 15-HETE leads to development of PAH in rodents. We recently showed that 15-HETE is the endogenous agonist for the G-protein coupled receptor 39 (GPR39) present in vascular smooth muscle cells.Hypothesis:We, therefore, hypothesized that global deletion of GPR39 (knock-out [KO] mice) would protect from PAH by removing the receptor through which 15-HETE causes vasoconstriction.Methods:Accordingly, 13 wild-type (WT) and 16 KO mice were placed in a hypoxia chamber (10% O2). Litter-mate controls (7 WT and 13 KO) were subjected to normoxia (room air, 21% O2). At the end of 4 weeks heart rate as well as aortic and right ventricular (RV) pressures were measured (latter using micromanometer-tipped catheter), and the animals were then euthanized for measurement of RV wall thickness and RV size from which RV wall stress was calculated.Results:Heart rate and systolic blood pressure were not different between the 4 groups.WT hypoxic animals developed PAH with peak RV systolic pressures (RVSP) being significantly higher than normoxic WT and hypoxic WT and hypoxic KO mice. (Figure 1) Similar results were noted for RV end-diastolic pressure (Figure 2) and RV wall stress (Figure 3).Conclusions:By deleting GPR39, the target for 15-HETE, we were able to prevent hypoxia induced PAH and RV dysfunction. Pharmacological inhibition of GPR39 may open new frontiers in the treatment of PAH.

Circulation, Volume 150, Issue Suppl_1, Page A4134837-A4134837, November 12, 2024. Background:Mitochondrial dysfunction is linked to myocardial ischemia-reperfusion (I/R) injury. Checkpoint kinase 1 (CHK1) could facilitate cardiomyocyte proliferation and cardiac repair post myocardial infarction, however, its role on mitochondrial function in I/R injury remains unknown.Research Questions:The purpose of this study is to explore the potential effects and mechanisms of CHK1 on mitochondrial homeostasis during myocardial I/R injury.Methods:To investigate the role of CHK1 on mitochondrial function following I/R injury, cardiomyocyte-specific knockout/knock-in mouse models were generated. Mass spectrometry-proteomics analysis and protein co-immunoprecipitation assays were conducted to dissect the molecular mechanism of CHK1. The interaction between CHK1 and SIRT1 was explored using truncated plasmids.Results:CHK1 was downregulated in myocardium post I/R and neonatal mouse cardiomyocytes (NMCMs) post oxygen-glucose deprivation/re-oxygenation (OGD/R).In vivo, CHK1 overexpression protected against myocardial I/R injury, while heterogenous CHK1 knockout exacerbated cardiomyopathy.In vitro, CHK1 inhibited OGD/R-induced cardiomyocyte apoptosis and bolstered cardiomyocyte survival. Mechanistically, CHK1 attenuated oxidative stress and preserved mitochondrial metabolism in cardiomyocytes under I/R. Moreover, disrupted mitochondrial homeostasis in I/R myocardium was restored by CHK1 through the promotion of mitochondrial biogenesis and mitophagy. Through mass spectrometry analysis following co-immunoprecipitation, SIRT1 was identified as a direct target of CHK1. The 266-390 domain of CHK1 interacted with the 160-583 domain of SIRT1. Importantly, CHK1 phosphorylated SIRT1 at Thr530 residue, thereby inhibiting SMURF2-mediated degradation of SIRT1. CHK1 Δ390 amino acids (aa) mutant functioned similarly to full-length CHK1 in scavenging ROS and maintaining mitochondrial dynamics. Consistently, cardiac-specific SIRT1 knockdown partially attenuated the protective role of CHK1 in I/R injury.Conclusions:Our findings revealed that CHK1 mitigates I/R injury and restores mitochondrial dynamics in cardiomyocytes through a SIRT1-dependent mechanism.

Circulation, Volume 150, Issue Suppl_1, Page A4129523-A4129523, November 12, 2024. Introduction:Patients with diabetes are at higher risk of chronic limb-threatening ischemia (CLTI), a severe form of peripheral artery disease (PAD) causing restricted blood flow to the lower limbs due, in part, to impaired angiogenesis. However, the role of microRNAs (miRNAs) in diabetic CLTI remains poorly understood. By integrating plasma miRNA sequencing data from PAD patients with diabetes with a diabetic CLTI mouse model, we have recently identified the conserved miRNA miR-1282 that is in cis-antisense orientation to SERF2, a gene associated with amyloid aggregation. Therefore, we hypothesize that miR-1282 orchestrates endothelial angiogenesis and proteostasis during diabetic CLTI.Methods:Using miR-1282 overexpression or SERF2 knockdown studies, we characterized mouse orthologs of human miR-1282 and SERF2 for angiogenesis, apoptosis, protein aggregation, and oxidative stress in diabetic mouse skeletal muscle endothelial cells (ECs). In vivo, miR-1282 mimics were delivered intramuscularly to assess their impact on blood flow recovery, angiogenesis, and protein aggregation. Mechanistic insights in ECs were gained via RNA-seq, predictive algorithms, and proteomic analyses.Results:miR-1282 inhibited the expression of its cis-antisense target SERF2 by 98%. miR-1282 is a hypoxia-induced endothelial-enriched miRNA, and its expression was inversely correlated with SERF2 expression. miR-1282 levels were markedly reduced after femoral artery ligation (FAL) in diabetic db/db mice. Overexpression of miR-1282 or SERF2 knockdown enhanced angiogenesis and reduced protein aggregation, apoptosis, and oxidative stress in both normal and hypoxic conditions in vitro. Delivery of miR-1282 mimics in db/db mice improved blood flow recovery by 108% and angiogenesis by 98%, and reduced protein aggregation by 48% and tissue necrosis. Coupling RNA-seq profiling and prediction algorithms of ECs upon miR-1282 overexpression or SERF2 knockdown revealed EREG, BAG5, CASP3, ARG1, and HSP90AA1 as potential downstream regulators. Pathway enrichment analysis implicated inhibition of endothelial apoptosis, ER stress, and protein stability among the most dysregulated processes.Conclusion:A novel mouse ortholog of human miR-1282 augments endothelial functions and diminishes protein aggregation in diabetic CLTI via suppression of its cis-antisense target SERF2. These findings uncover new potential therapeutic targets in treating diabetic CLTI.

Circulation, Volume 150, Issue Suppl_1, Page A4135229-A4135229, November 12, 2024. Background:Endothelial glycocalyx (eGC) is a layer of glycosaminoglycans adhered to proteoglycans that cover the inner surface of the vessels. The integrity of this structure sustains some vascular properties such as shear stress-induced nitric oxide release and the prevention of platelets and neutrophils adhesion on the vessel surface. eGC shedding could contribute to atherosclerotic plaque vulnerability and acute myocardial infarction (AMI) installation. This research investigated whether acute eGC damage and microvascular dysfunction occurred during AMI.Methods:Sublingual microcirculation was assessed through Capiscope HCVS Handheld Video Capillaroscopy System (KK Technology, Honiton, UK) during the first 72h of hospital admission because of ST-elevation AMI (before) and repeated around six months later (after). All images were automatically analyzed using the GlycoCheck (Alpine, UT, USA), which estimated the perfused vascular density (PVD), the red blood cell (RBC) filling of the vessels, the perfused boundary region (PBR) in µm, an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). This score ranges from 0-10; the lower its numerical value, the greater the microvascular impairment.Results:Twenty patients were included (61±10 years old, 85% males, 55% anterior AMI, 70% hypertension, 25% diabetes, 45% current smoker, all underwent primary PCI). The time between the two sublingual assessments was 188±31 days. The PBR [1.96±0.22µm vs. 1.84±0.19µm]; p=0.047 and flow-adjusted PBR [1.40±0.25µm vs. 1.24±0.16µm]; p=0.045 decreased statistically significant over time. The RBC filling [71.56±4.33% vs. 74.02±3.88%]; p=0.016 and the MVHS [4.28 (interquartile range (IRQ) 3.38-4.90) vs. 5.04 (IQR 4.37-6.00)]; p=0.044 increased statistically significant over time. The PVD [500±86 x10-2µm/mm vs. 522±84×10-2µm/mm]; p=0.255 did not modify over time.Conclusion:This finding was compatible with eGC shedding and microvascular dysfunction during AMI and later reconstitution of this structure after six months.

Circulation, Volume 150, Issue Suppl_1, Page A4146699-A4146699, November 12, 2024. Background:Growing evidence suggests that blunted blood pressure and heart rate responses to acute psychological stress independently associate with an increased risk of adverse outcomes in individuals with CHD, but assessment of mental stress reactivity in clinical settings is resource intensive. An alternative approach is to passively measure stress physiology at home with wearables, which is easier to translate into clinical practice. We tested the hypothesis that blunted mental-stress hemodynamic reactivity in the lab is associated with digital biomarkers of autonomic inflexibility at home.Methods:We conducted a mental stress test in 239 participants (age < 60 years) with an MI within 8 months. Participants underwent a speech stressor task in front of an audience to induce mental stress, during which blood pressure and heart rate were measured repeatedly during a baseline 15-minute rest period and 5-minute stress challenge. Participants went home with a 7-day Holter monitor to measure autonomic function. We examined vagal autonomic inflexibility with deceleration capacity (DC), a digital biomarker calculated via phase rectified signal averaging of heart rate intervals. We also examined low frequency (LF) heart rate variability (HRV), an indirect measure of baroreceptor sensitivity. We measured mean values from 5-minute windows during sedentary periods only to avoid confounding due to physical activity. We used multivariable linear regression models to adjust for potential confounding due to age, beta-blockers, and sex.Results:The mean age was 52 years, 51% were black, and 36% were women. Lower DC most strongly associated with a blunted change in heart rate during acute mental stress challenge (adjusted p

Circulation, Volume 150, Issue Suppl_1, Page A4147293-A4147293, November 12, 2024. Introduction:GLP1 receptor agonists (GLP1RA) improves outcomes by reducing event rates of myocardial infarction (MI). Whether GLP1RA also reduce MI size by ameliorating myocardial ischemia-reperfusion (I/R) injury remains incompletely understood. The main cardioprotective pathways to induce myocardial salvage are RISK (activation of Akt) and SAFE (activation of STAT3). We hypothesized that semaglutide increases myocardial salvage, reduces myocardial infarction (MI) size, improves left ventricular (LV) systolic function, and decreases apoptosis and oxidative stress in a porcine model of I/R mediated via activation of both RISK and SAFE pathwaysMethods:Myocardial I/R injury was induced in Yorkshire pigs by balloon occlusion of the proximal LAD for 60 min, followed by reperfusion. Animals randomly received semaglutide 0.5mg the day before I/R (to mimick patients on chronic GLP1RA), or saline for controls (n=6/group). Animals were evaluated at 1-day post-MI with cardiac MRI, 3D-echo, histology (apoptosis and oxidative stress) and molecular biology (activation of RISK and SAFE). To mechanistically study the effect of each molecular pathway, two additional groups were treated with GLP1RA+wortmannin (inhibitor of RISK) and GLP1RA+AG490 (inhibitor of SAFE)Results:Despite similar of myocardium at risk in both groups (42.8±2.2% vs 42.2±2.7%, p=NS), semaglutide significantly reduced LGE-determined MI size (33.1±2.3% vs 41.1±2.8% of LV, p

Circulation, Volume 150, Issue Suppl_1, Page A4147290-A4147290, November 12, 2024. Introduction:Alcohol consumption is associated with an increase in pro-inflammatory cytokines. Acute non-infectious pericarditis may be a consequence of the alcohol-related inflammatory process. This study investigates the association between excessive alcohol consumption and the risk of acute pericarditis and myocarditis.Hypothesis:Alcohol use may be associated with myocarditis and pericarditis through oxidative stress, immunological dysfunction, and direct toxicity to the heart muscle.Methods:This is a cross-sectional study of participants in the All of Us study at the time of enrollment. Alcohol use, our primary exposure was measured using the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) score. Participants were stratified based on their AUDIT scores into Low risk-(males with Audit less than 4, females with Audit less than 3),moderate risk (AUDIT 4-5 in males, 3-5 in females), high risk (AUDIT 6-7 in both males and females) severe risk (AUDIT 8-12 in both males and females). The diagnosis of pericarditis and myocarditis was identified using electronic health records at the time of enrollment. The study adjusted baseline age, sex, race, educational status, income, health insurance, and smoking status. Logistic regression models were used to evaluate the association between alcohol intake and myocarditis/pericarditis. Models were adjusted for age, sex, race, educational status, income, health insurance, and smoking status.Results:Out of 135,010 eligible participants at baseline, 220 cases of myocarditis and pericarditis were detected. People with severe alcohol intake were (n=4825) more likely to be male (n, 3125, 64.8%%), less likely to be insured (n, %=4320, 89.5%) and less likely current cigarette smokers (n, %= 1007, 9.3%). The odds of developing myocarditis or pericarditis were not statistically significantly different with increasing AUDIT-C categories as compared to never- after adjusting for confounders. (table 1)Conclusion:There was no significant association found between higher AUDIT scores and an elevated risk of myocarditis and pericarditis.

Circulation, Volume 150, Issue Suppl_1, Page A4145480-A4145480, November 12, 2024. Introduction:Acute respiratory distress in the peripartum period can occur from a variety of reasons including pulmonary or cardiac causes. Careful integration of the history, physical examination and imaging studies is crucial to make a definitive diagnosis.Case presentation:The patient is a 22-yr-old G1P0 African American woman with no significant medical history who had two unsuccessful external cephalic versions and required Cesarean section. Intraoperatively, she became dyspneic and hypoxic. She had labored breathing, tachycardia, scattered wheezes and hypotension. She had acute pulmonary edema, requiring endotracheal intubation. PA catheter placement revealed cardiac output of 3.7 L/min, Pulmonary artey pressure was 37/27 mmHg and SPO2 of 80% on 100% FiO2. Transthoracic echocardiogram (TTE) revealed moderately reduced left ventricular ejection fraction, (LVEF) 30-35% and moderate mitral regurgitation. She had preserved apical LV function with reduced contractility in the basal segments suggestive of reverse Takotsubo syndrome. RV size and function were normal, making significant pulmonary embolism less likely. CXR revealed interstitial edema. EKG had sinus tachycardia. Peak troponin I was 3.3ng/mL and Lactic acid 4.2 mmol/L. Patient received IV diuretic and inotropic support with Norepinephrine, Epinephrine and Milrinone. She was extubated after 2 days. TTE four days later revealed recovery of LVEF to 53%. Three weeks later, she was asymptomatic. Cardiac MRI showed normal LVEF 58% and no wall motion abnormalities.Discussion:The patient had acute pulmonary edema and systolic dysfunction.In the absence of chest pain or ST elevation on EKG, spontaneous coronary dissection was unlikely. Takotsubo cardiomyopathy (TMC) is an acute but transient cardiac dysfunction following significant physical or emotional stress. Attempted external cephalic version may have triggered TMC. It is important to distinguish between TCM and Peripartum cardiomyopathy (PPCM) in these patients as it may prevent the continuation of long term medical therapy for heart failure. PPCM has a more gradual onset. Quick normalization of her LV function strongly favors that she experienced Takotsubo, not Peripartum cardiomyopathy.Conclusion:Making an accurate diagnosis of Takotsubo cardiomyopathy by serial echocardiography to demonstrate quick improvement in LV function has long-term implications regarding future pregnancies and prognosis.