Risultati per: Nelle donne lo stress danneggia la salute dell’intestino

Circulation, Volume 150, Issue Suppl_1, Page A4138348-A4138348, November 12, 2024. Methods and Results:We describe a comprehensive characterization of the AVICs nucleus landscape as determined by transmission electron microscopy (TEM) of samples obtained from CAVD patients. Turbulence led to nuclear envelope integrity lose in AVICs cultured in shear stress experiments, with three different fluid conditions [static (ST), laminar stress (LS), and oscillatory stress (OS)], indicated by Western blot and immunofluorescence (IF). Silencing lamin A/C (LMNA) through small interfering RNA (siRNA), accelerated nuclear envelope damage , as indicated by Western blot, qPCR, and immunofluorescence (IF). The formation of Z-DNA and its co-localization with Z-DNA binding protein (ZBP1) was observed due to the nuclear envelope damage by IF. Western blot, qPCR, IHC and IF confirmed Z-DNA-induced inflammation in AVICs through the ZBP1-RIPK3-NF-κB signaling pathway. ZBP1 and RIPK3 knockdown with siRNA markedly reduced the protein level of osteogenic markers alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and bone morphogenetic protein 2 (BMP2) in VICs. In vivo, aortic valve disease was constructed by direct wire injury (DWI), and we showed that overexpression of LMNA by adeno-associated virus significantly decelerated the progression of aortic valve lesion induced by DWI in mice.Conclusion:Excessive mechanical stress can induce damage to the nuclear envelope of AVICs by causing cytoskeletal remodeling, initiating the formation of Z-DNA, and hastening the calcification process in AVICs and CAVD.

Circulation, Volume 150, Issue Suppl_1, Page A4143847-A4143847, November 12, 2024. Introduction:Our previous studies have shown that sustained activation of the DNA damage response (DDR) in cardiomyocytes leads to p53/p21 activation and cardiac dysfunction. Although the DDR generally involves molecules in DNA replication and repair pathways, the non-proliferative nature of cardiomyocytes suggests a cardio-specific DDR mechanism. However, our understanding of DDR in cardiomyocytes remains limited. Here, we aim to use CRISPR interference (CRISPRi) knockdown screens to identify genes critically involved in DDR regulation in human cardiomyocytes. We hypothesize that identifying these gene clusters may allow us to develop methods to prevent cardiac dysfunction by suppressing DDR in cardiomyocytes.Methods and Results:We established a human iPS cell line stably expressing dCas9-KRAB, which allows CRISPRi-mediated gene knockdown, and differentiated the cells into cardiomyocytes. The resulting human iPS cell-derived cardiomyocytes (hiPSCMs) showed the achievement of approximately 80% knockdown efficiency after gRNA transfection. We stimulated the hiPSCMs with H2O2and quantitatively evaluated the expression levels of the DDR markers γH2AX and p21 by immunostaining using the Operetta®high content imaging system. The DDR markers showed a significant concentration-dependent increase in response to H2O2administration. For arrayed CRISPRi screening, we constructed a gRNA library targeting 437 DDR-related genes. Using this library, we knocked down each DDR-related gene in hiPSCMs followed by H2O2stimulation. We quantified the expression levels of DDR markers by calculating the fluorescence intensity ratios relative to control after gene knockdown, and standardized them to calculate Z scores for all 437 genes. The screening successfully revealed the differential impact of each gene knockdown on γH2AX and p21 expression. We identified 71 genes that significantly affected their expression (Z-score < -1 or > 1). Mapping these genes to DDR pathways highlighted the differential impact of gene knockdown within the same pathway, and stratified their importance in cardiomyocytes.Conclusions:Arrayed CRISPR screening using hiPSCMs revealed differential functional significance of DDR-related genes in cardiomyocytes, identifying 71 genes of particularly significant importance. These findings provide a critical understanding of the cardio-specific DDR pathway and important clues for establishing an appropriate method to suppress DDR in the failing heart.

Circulation, Volume 150, Issue Suppl_1, Page A4142510-A4142510, November 12, 2024. Background:An acute hyperglycemic status is reportedly associated with poor prognosis in patients with acute cardiovascular diseases. Although the stress hyperglycemia ratio (SHR) is a novel index to accurately represent the hyperglycemic condition on admission, relations between SHR and clinical outcomes are not fully evaluated in a setting of acute myocardial infarction (MI).Methods:This retrospective, multicenter registry study included 2,386 patients with acute MI undergoing percutaneous coronary intervention. SHR was calculated as a blood glucose level on admission divided by the estimated average glucose derived from a glycated hemoglobin level. The co-primary endpoints of this study included heart failure (HF)-related events (a composite of all-cause death and worsening and hospitalized HF) and major atherosclerotic cardiovascular events (MACE) (a composite of all-cause death, recurrent MI, and ischemic stroke), during the index hospitalization and after discharge.Results:Of the 2,386 patients, 890 (37.3%) had diabetes, and the median SHR was 1.17 [0.99, 1.45]. HF events and MACE occurred in 680 (28.5%) and 233 (9.8%) during hospitalization. SHR was identified as a factor significantly associated with both in-hospital HF events (adjusted odds ratio 1.65, 95% confidence interval 1.18-2.29, p=0.003) and MACE (adjusted odds ratio 1.50, 95% confidence interval 1.10-2.03, p=0.009). Among 2,017 patients who survived to discharge and had follow-up information, 195 (9.7%) and 214 (10.6%) experienced HF events and MACE during the median of 536 days after discharge. Patients with the high SHR ( >1.45, 4th quartile) had an increased risk of HF events than those with SHR ≤1.45, while the incidence of MACE after discharge did not differ significantly between the two groups (Figure). The multivariable analysis confirmed the association of SHR with long-term HF events.Conclusions:In patients with acute MI, SHR was predictive of in-hospital outcomes including HF events and MACE, while after discharge, the higher SHR was associated with a higher HF risk but not with MACE. Further studies are needed to elucidate the underlying mechanisms and potential incremental benefit of SHR in stratifying patient risks after MI.

Circulation, Volume 150, Issue Suppl_1, Page A4138517-A4138517, November 12, 2024. Background:Exercise stress echocardiography is routinely used for risk stratification and diagnosis of myocardial ischemia in low-to-intermediate risk patients with suspected coronary artery disease (CAD). Discrepancies between exercise electrocardiography (EKG) and echocardiography (ECHO) are common in clinical practice. Prior literature suggests that patients with discordant stress test results generally have worse outcomes, though the extent of epicardial atherosclerotic disease remains unclear. Coronary computed tomographic angiography (CTA) has gained a class I recommendation for the assessment of atherosclerotic burden per ACC/AHA chest pain guidelines. Using non-invasive fractional flow reserve (CT-FFR), the functional significance of lesions can also be assessed. This study investigates the incidence and burden of CAD in patients with discordant exercise echocardiography findings.Methods:Patients aged 18 or older who had exercise echocardiography followed by CTA from January 1, 2013, to January 31, 2023, were retrospectively enrolled in this study and categorized into two discordant result groups: EKG+/ECHO- or EKG-/ECHO+. Those who failed to achieve the target heart rate or had a paced rhythm/left bundle branch block on baseline EKG were excluded. CTA findings were classified as no CAD, non-obstructive CAD (

Circulation, Volume 150, Issue Suppl_1, Page A4125939-A4125939, November 12, 2024. Background:Prophylactic steroids are often used to reduce the systemic inflammatory response to cardiopulmonary bypass in infants undergoing heart surgery. The STRESS trial found that the likelihood of a worse outcome did not differ between infants randomized to methylprednisolone vs placebo in a risk-adjusted primary analysis (adjusted odds ratio [OR], 0.86; 95% CI, 0.71 to 1.05; P=0.14). However, secondary unadjusted analyses showed possible benefits with methylprednisolone. We re-analyzed the STRESS trial using Bayesian analytics to assess probability of benefit with methylprednisolone.Methods:We used a covariate-adjusted proportional odds model using the original STRESS trial model covariates and primary outcome (a ranked composite of death, transplant, major complications and post-op length of stay). We assessed effect thresholds from OR 0.6 to 1.25 (OR 1 conveys harm). We assumed a neutral probability of benefit vs harm with weak prior belief (SD of the normal prior distribution = 0.425). In sensitivity analyses, we evaluated pessimistic (5%-30% prior likelihood of benefit), neutral and optimistic (70%-95% prior likelihood of benefit) prior beliefs, and controlled strength of prior belief as weak (SD = 0.425), moderate (SD = 0.215) and strong (SD = 0.135). We compared posterior distribution of the OR under these priors with the reference results under the vague prior distribution. Analyses consisted of 10 Markov Chain Monte Carlo simulations each consisting of 2000 iterations with a 1000 iteration burn-in to ensure proper posterior convergence.Results:In primary analysis, the posterior probability of benefit from methylprednisolone was 92% and the probability of harm was 8%. The mean absolute benefit was 12%. In sensitivity analyses, the probability of benefit was ≥ 79% for all informative priors except the most pessimistic (Table/Figure).Conclusion:In Bayesian re-analysis of the STRESS trial, probability of benefit with prophylactic methylprednisolone is high and harm is unlikely. Assessing probability of benefit or harm may be more informative than frequentist analytics relying on a p-value threshold. Another advantage is the ability to consider a range of prior evidence.

Circulation, Volume 150, Issue Suppl_1, Page A4146135-A4146135, November 12, 2024. Background:Epicardial adipose tissue (EAT) is increasingly recognized as a key factor in the development of atrial fibrillation (AF). In addition to direct myocardial infiltration by adipocytes affecting conduction properties, EAT may also promote an arrhythmogenic substrate through paracrine and endocrine effects. EAT was shown to preferentially generate oxidase-dependent reactive oxygen species (ROS) when compared to subcutaneous fat. While a role for myocardial ROS in the development of AF is well established, a separate role for EAT oxidative stress remains unexplored.Hypothesis:Oxidative stress in the EAT contributes to atrial electrical remodeling and development of AF.Aims:Determine the effect of EAT-restricted gene therapy with NOX2 shRNA on atrial electrical remodeling in the short-term canine atrial tachypacing (ATP) model of AF.Methods:A single-chamber pacemaker was inserted for the ATP model. Animals developed persistent AF after 4-6 weeks, after which the atria were harvested. Unpaced animals were used as controls. Expression of NOX2 in the EAT was assessed by qPCR. EAT oxidative stress was determined by IHC for 8-OHdG, a marker of DNA oxidative damage. A subset of animals underwent an open-chest gene injection procedure restricted to the EAT (with a plasmid expressing NOX2 shRNA or a scrambled sequence) prior to initiation of ATP for 9 days. A terminal EP study determined regional atrial ERP and AF inducibility.Results:NOX2 expression was significantly increased in the EAT of animals with ATP-induced AF when compared to unpaced controls (Panel A, p

Circulation, Volume 150, Issue Suppl_1, Page A4141934-A4141934, November 12, 2024. Introduction:Heightened psychosocial stress is a CVD risk factor. While stressors are common and often co-occur, identifying sources and patterns of psychosocial stress exposure may provide insight into individual susceptibility to CVD. Therefore, we sought to identify and examine the longitudinal associations of baseline psychosocial stress subgroups with CVD events in MESA.Methods:Data from 6,349 adults (aged: 62.2±10.2 years; 52.9% women) from the MESA cohort with no prior CVD event at baseline (years 2000-2002) were used in this analysis. Latent class analysis (LCA) was used to specify distinct stress subgroups based on 6 variables: chronic burden, neighborhood safety, adequate food shopping, neighborhood noise, lifetime- and past-year discrimination. Five classes were determined after examining traditional fit indices. Adjudicated fatal and nonfatal CVD events were ascertained in annual follow-up visits through the year 2019. Cox proportional hazards models with sequential adjustment of baseline variables were used to examine the associations between subgroup membership and CVD events.Results:Five distinct stress subgroups were identified via LCA and were labeled “moderate neighborhood noise” (12.1%), “excessive noise/crime” (6.4%), “elevated on all” (6.3%), “high discrimination/safe neighborhood” (21.4%), “optimal” (53.8%) (see figure). By the year 2019, 1,121 participants had experienced a CVD event. Membership in the “elevated on all” and “high discrimination/safe neighborhood” subgroups (see table) were associated with higher risk of a CVD event when adjusted for sociodemographic characteristics and cardiovascular health metrics. However, when adjusted for measures of anxiety and depression, possible mediators, only membership in the “high discrimination/safe neighborhood” subgroup was associated with increased risk of a CVD event.Conclusions:Among 5 distinct stress subgroups those experiencing high discrimination had higher risk for CVD events.

Circulation, Volume 150, Issue Suppl_1, Page A4146032-A4146032, November 12, 2024. Background:Stress testing is a well-established non-invasive method commonly used in clinical practice for patients with angina. However, its benefit in diabetic patients after coronary intervention remains unclear. This systematic review aims to address this knowledge gap by evaluating the impact of routine stress testing in this specific patient population.Research Question:Does routine stress testing improve outcomes in diabetic patients with prior revascularization?Goals:We aimed to perform a systematic review and meta-analysis of studies that evaluated death, MACE and repeated revascularization episodes in diabetic patients who have prior coronary intervention.Methods:We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCT) and cohort studies evaluating diabetic patients who underwent cardiac revascularization and reporting the following outcomes: (1) Myocardial Infarction (MI) and Cardiovascular Death; (2) Ischemia; and (3) Repeat Revascularization. Statistical analysis was performed using Open Meta and heterogeneity was assessed with I2statistical.Results:We included 16924 patients from 16 studies, of which 15 were observational cohort studies and 1 was a RCT. All patients were diabetics and had a history of revascularization. Follow-up ranged from 1 to 5.2 years. The mean patient age was 60.8±9.5 years and 75% were male. MI and cardiovascular death was found in 9.8% (95% CI; range 6.8-12.8%; p

Circulation, Volume 150, Issue Suppl_1, Page A4147100-A4147100, November 12, 2024. Introduction:Perceived stress is known as the feeling of uncontrollability in one’s life and the inability to cope with the amount of stress one is experiencing due to one’s circumstances. There is evidence indicating that perceived stress may be a risk factor for cardiovascular disease (CVD). However, it is unclear whether perceived stress is associated with higher left ventricular mass index (LVMI), a measure of target organ damage and strong predictor of CVD.Aim:We examined the association between perceived stress and LVMI.Methods:The Masked Hypertension Study is a multi-site study that assessed the prevalence and predictors of masked hypertension in working adults from the New York Metropolitan area. A total of 1011 participants were recruited for the study; 826 participants completed the Perceived Stress Scale questionnaire and an echocardiogram. The perceived stress scale is a 14-item likert scale that assesses different situations that affects our perceived stress or our feelings in certain situations. It has a scale of 1 to 5 with 1 being never to 5 being very often. LVMI was determined according to the 2D method based on the American Society of Echocardiography (ASE) recommendations.Linear regression models were specified predicting LVMI from perceived stress. Covariates were sex, race/ethnicity, age, BMI, systolic bp, diastolic bp, and caregiving status.Results:Of the 826 participants, 40.7% were male, 6.9% were Black, 11.9% were Hispanic/Latinx , and 48.79% were caregivers. Mean (SD) age was 45.3 (10.3) years, mean body mass index was 27.6 (5.3) kg/m2, and mean SBP and DBP were 114.7 (12.0) and 74.8 (8.5). Mean perceived stress score was 21.8 (7.6) and mean LVMI was 63.3 (15.7) gm/m2.Contrary to our hypothesis, perceived stress was not significantly associated with LVMI, B = -0.00, 95% CI: -0.13, 0.13, p= 0.98.Conclusion:There was not an association between perceived stress and LVMI. Future research should examine whether other types of stresses/stressors are related to LVMI and the implications of this for patients and their health.

Circulation, Volume 150, Issue Suppl_1, Page A4142430-A4142430, November 12, 2024. Background:Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (OHT). Noninvasive methods to detect CAV and risk stratify OHT patients are needed. The value of fully quantitative stress cardiac magnetic resonance imaging has been recently validated and may be a promising technique for OHT surveillance. We aimed to evaluate the feasibility of quantitative stress CMR after OHT.Methods:We enrolled asymptomatic OHT recipients without coronary artery disease to undergo regadenoson stress CMR (1.5T GE HealthCare) with cine imaging, tissue mapping, and late gadolinium enhancement (LGE) imaging for routine CAV surveillance. Using the dual sequence technique, quantitative perfusion values were determined using Fermi deconvolution. Myocardial perfusion reserve (MPR) was calculated as the ratio of stress to rest myocardial blood flow (MBF).Results:Fifty-three subjects (mean age 47.06 ± 17.14 years) were included. OHT recipients (n=11, mean 6.77 ± 4.34 years post-transplant) were compared with healthy controls (n=43). No life-threatening adverse events, brief or prolonged atrioventricular block or other arrhythmias occurred with regadenoson. Coronary angiography was performed in 9 OHT patients before CMR, with an average of 1.99 ± 2.05 years between studies. No visual inducible ischemia was reported. Post OHT, rest MBF was significantly higher (1.69 ± 0.52 mL/g/min vs 1.01 ± 0.24 mL/g/min, p=0.004) and stress MBF was lower (2.33 ± 0.69 mL/g/min vs 2.95 ± 0.88 mL/g/min, p=0.02) compared to controls. MPR was significantly lower in OHT recipients compared to controls (1.46 ± 0.51 vs 3.11 ± 1.12, p

Circulation, Volume 150, Issue Suppl_1, Page A4142424-A4142424, November 12, 2024. Background:Risk assessment for chronic thromboembolic pulmonary hypertension (CTEPH) remain challenging. Stress hyperglycemia represents the regulation of glucose metabolism in response to stress. Meanwhile, stress hyperglycemia ratio (SHR) is recently found to reflect true acute hyperglycemic status. However, the relationship between SHR and adverse prognosis is uncertain. This study aimed to investigate the prognostic value of SHR in CTEPH patients.Methods:A total of 451 CTEPH patients with available baseline SHR measurement were enrolled between February 2014 to July 2023 at Fuwai hospital. The predictive values of SHR for adverse events were assessed.Results:During a median follow-up of 21 months, 89 (19.7%) CTEPH patients experienced adverse clinical outcomes. Kaplan-Meier curve analysis revealed that the cumulative adverse event rates were significant higher in the SHR≥0.747 with CTEPH patients, compared with patients in the SHR

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 A4137735-A4137735, November 12, 2024. Background:Aortic aneurysms account for ~10,000 deaths annually in the USA. Oxidative stress is implicated in both abdominal (AAA) and thoracic (TAA) aneurysm formation, but the mechanisms are incompletely understood. We used a chemogenetic approach to modulate oxidative stress in the vascular wall by creating a transgenic mouse (DAAO-TGTie2) that expresses yeast D-amino acid oxidase (DAAO) driven by the endothelial Tie2 promoter. DAAO generates the reactive oxygen species hydrogen peroxide from D-amino acids. Vascular tissues contain L-amino acids, so yeast DAAO is quiescent until DAAO-TGTie2mice are provided with D-amino acids. Here we characterize the cellular and molecular consequences of vascular oxidative stress in DAAO-TGTie2mice.Hypothesis:Chronic oxidative stress in the vascular wall causes arterial dysfunction.Aim:To characterize the phenotype of DAAO-TGTie2mice after oxidative stress induction in vascular endothelium.To identify the mechanisms whereby vascular oxidative stress causes arterial dysfunction and hypertension.Methods:Systolic blood pressure and aortic sonography were measured weekly in D-alanine-fed DAAO-TGTie2. Proteomic analyses were used to identify mechanistic targets, which were validated using biochemical and immunohistochemical methods.Results:D-alanine-fed DAAO-TGTie2mice develop systolic hypertension and abdominal but not thoracic aortic aneurysms; treated mice die in >3 months with burst abdominal aortic aneurysms. Transgene expression is similar in abdominal and thoracic endothelium. Levels of oxidative stress markers (oxidized proteins, lipid, and DNA) were similar in thoracic and abdominal aorta. Proteomic analyses established phenotypic switching in abdominal but not thoracic aorta, and also revealed activation of the oxidant-activated kinase ASK1 and of the MAP kinase cascade in abdominal but not thoracic aorta. Immunoblot analyses showed a marked decrease in JNK1 phosphorylation by phosphatase DUSP3 and an increase in vascular KLF4, leading to phenotypic switching of contractile to synthetic VSMCs.Conclusion:Chronic chemogenetic oxidative stress induces hypertension and abdominal aortic aneurysm formation caused by KLF4-dependent VSMC phenotypic switching.

Circulation, Volume 150, Issue Suppl_1, Page A4139600-A4139600, November 12, 2024. Background:Cardiac injury after subarachnoid hemorrhage (SAH) is a well-recognized phenomenon with electrocardiogram (ECG) changes, arrhythmias and myocardial dysfunction. Neurocardiac injury has been commonly reported with increased severity of SAH, however much of the evidence has focused on high grade SAH requiring hemodynamic support or mechanical ventilation. In this study we focused on neurocardiac injury with high grade World Federation of Neurological Surgeons (WFNS) grade 3-5 SAH requiring intensive care management.Methods:Patients admitted to our intensive care unit from 2009-2019 with an WFNS 3-5 aneurysmal SAH with an echocardiogram within 7 days of admission were included in our study. Electrocardiogram, cardiac biomarkers and data regarding mortality and neurological complications were collected retrospectively.Results:A total of 242 patients were included in our study analysis with 11 (5%), 89 (37%), and 142 (59%) had WFNS grade 3, 4 or 5 SAH, respectively. Of the 95 patients that underwent echocardiography in the first week, 38 (40%) had a reduced ejection fraction, which was mild (LVEF 40-52%) in 13 (14%), moderate (LVEF 30-39%) in 14 (15%), and severe (LVEF < 30%) in 11 (12%). Independent predictors of reduced ejection fraction included a lower presenting GCS score (OR 1.2 per one point reduction in (Glasgow Coma Score) GCS, 95% CI 1.0-1.5, p = 0.03), elevated troponin T concentration (OR 6.1, 95% CI 1.2-31.3, p = 0.03) and T wave inversion on ECG (OR 9.1, 95% CI 1.6-52.3, p = 0.01). In patients with reduced ejection fraction, classical apical wall motion abnormality was more prevalent in older populations (median age 64 years (apical) vs 50 years (basal wall motion abnormality) and 52 years (other) p = 0.03). In all wall motion abnormality groups, there was a female predominance. Classic Takotsubo wall motion was associated with an anterior SAH aneurysm location (p = 0.03) and highest proportion of moderate to severe LV dysfunction (p = 0.04). ICU mortality did not differ based on the pattern of wall motion abnormalities.Conclusion:Predictors of neurocardiac injury in high grade SAH include troponin elevation, T wave abnormalities and lower presenting GCS. Aneurysm location was associated with wall motion abnormalities and degree of LV dysfunction. Patients with WFNS 3-5 SAH are at increased risk of neurocardiac injury. ECG changes, cardiac biomarker elevation and aneurysm location can help identify patients who warrant echocardiography.

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 A4137913-A4137913, November 12, 2024. Background:Cardiac sarcoidosis (CS) was characterized by formation of granulomas in the heart. Enhancement in myocardial inflammatory activity and oxidative stress is a crucial cause of major cardiovascular adverse events (MACE). Although immunosuppressive therapy is recommended for active CS, there is no established markers for treatment and prognosis.Hypothesis:We hypothesized that the inflammation and oxidative stress in heart were associated with MACE after steroid therapy.Aims:We identified prognostic markers for MACE in patients with CS after steroid therapy.Methods:This study was a prospective observational cohort study. Patients with CS diagnosed according to Japanese criteria were enrolled in this study. Patients with abnormal accumulation of18F-FDG in heart were treated with steroids with standard guideline-recommended protocol.18F-FDG PET were performed after more than 6 months of induction. Urinary 8-hydroxy-2′-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage, and indices of cardiac and renal function were measured. The major outcome was a composite of the first sustained ventricular tachycardia (sVT) /sudden cardiac death (SCD), hospitalization for heart failure, and radiological relapse with exacerbation of clinical manifestation.Results:Fifty consecutive patients with CS underwent steroid therapy and followed up (median follow-up period of 58 months). 39 of 50 patients underwent 18F-FDG PET/CT more than 6 months after steroid therapy. During the follow-up period, 17 of 39 patients showed MACE, consisting of sVT/SCD (N= 11), hospitalization (N= 2) and radiological relapse (N= 4). A Cox proportional-hazard model showed that the U-8-OHdG and SUV max value of FDG-PET were independent predictors of MACE. ROC analysis revealed that the cut-off values of U-8-OHdG and SUV max for predicting the MACE were 11.6 ng/mg Cr (AUC 0.913, sensitivity 86.7%, specificity 90.0%) and 4.64 (AUC 0.878, sensitivity 76.5%, specificity 91.0%), respectively (Fig.1). Patients with a U-8-OHdG ≧11.6 ng/mg Cr or SUV max ≧4.64 had a significantly higher MACE risk (P values for U-8-OHdG and SUV max were both 0.001 by Log Rank analysis) (Fig.2). It is noted that U-8-OHdG