Search Results for: Come stress e attacchi di cuore sono collegati

Circulation, Volume 150, Issue Suppl_1, Page A4117345-A4117345, November 12, 2024. Introduction:Acute type A aortic dissection (ATAAD) is typically treated by replacement of the ascending aorta (+/- root) and proximal arch. However, 70-85% of patients have residual distal dissection post-repair, and 20-40% require late reoperation for aneurysmal degeneration of the distal aorta (ADDA). Since an individual patient’s risk of ADDA cannot be accurately predicted, current guidelines recommend lifelong aortic surveillance imaging for all patients.Hypothesis:Computational fluid dynamics (CFD) simulations of aortic hemodynamics post-repair can accurately identify patients at late risk of ADDA.Methods:We performed CFD simulations of 50 patients following hemi-arch replacement for ATAAD. Patient-specific 3D models were generated from the aortic root to iliac bifurcation (including arch branches) from postoperative 0.6mm contrast-enhanced CT angiograms taken

Circulation, Volume 150, Issue Suppl_1, Page A4141710-A4141710, November 12, 2024. Background:Stress perfusion CMR has excellent diagnostic and prognostic values in assessing chest pain syndromes. AI-guided methods may overcome complex scanning and increase clinical adaptation of stress CMR.Aim:To assess the benefits of AI-guided stress perfusion CMR.Methods:Consecutive patients with stable chest pain underwent stress CMR using either a standard scanning method (SOC) or an AI-assist (AIA) machine learning protocol to automate scan planning, plane prescription, sequence tuning, and image reconstruction. Scan duration, the ratio of scan preparation time over the entire scan duration, and scan quality using a 5-point scale were compared between AIA and SOC. Cox regression models were constructed to associate evidence of ischemia on stress CMR, by either scanning method, with composite endpoints including cardiovascular death, non-fatal MI, unstable angina hospitalization, and late CABG. A second composite endpoint included the performance of additional cardiac imaging tests (stress imaging and CCTA) and invasive coronary procedures after CMR.Results:Among 594 patients (62.8 ± 14 years), 29% underwent stress CMR with AIA. 26% had stress-perfusion ischemia, and 39% had LGE present. AIA stress CMR had lower scan duration (median 44.0 [IQR 40-47] vs. 52.5 min [IQR 46-60]; p

Circulation, Volume 150, Issue Suppl_1, Page A4147568-A4147568, November 12, 2024. Introduction:Cardiovascular disease (CVD) and cancer are among the leading causes of morbidity and mortality worldwide. Increasing evidence suggests that sociodemographic factors such as race, ethnicity, income, education, and stress levels significantly influence the prevalence and outcomes of these diseases. TheAll of UsResearch Program provides a unique opportunity to explore these disparities across a diverse U.S. population. This study aims to examine how sociodemographic disparities are associated with stress, CVD, and cancer outcomes. We hypothesize that higher perceived stress levels, lower income, lower education levels, and minority race/ethnicity groups are associated with higher incidences of CVD and cancer.Methods:Data from 55,505All of UsResearch program participants were analyzed. Key variables included age, race, ethnicity, education, household income, perceived stress level, and history of CVD and cancer. Descriptive statistics were used to summarize participant demographics. Multivariate logistic regression models were employed to examine the associations between sociodemographic factors and the outcomes of interest (CVD and cancer).Results:Older participants had a higher prevalence of both CVD (mean age: 60.8 vs. 50.5, p < 0.001) and cancer (mean age: 63.6 vs. 51.7, p < 0.001). Black/African Americans had a higher incidence of CVD (21.3% vs. 78.7%, p < 0.001), while Whites had a higher prevalence of cancer (5.3% vs. 94.7%, p < 0.001). Lower income and higher stress levels were also associated with higher CVD incidence (

Circulation, Volume 150, Issue Suppl_1, Page A4145174-A4145174, November 12, 2024. Background:Protein half-life and turnover are crucial for cellular function, especially under basal and stress conditions, often contributing to proteinopathies. While the impact of oxidative stress (OxS) on proteostasis is well-documented, the role of reductive stress, an overabundance of antioxidant status, in proteotoxic cardiac disease remains elusive.Hypothesis:Tested whether chronic reductive stress (cRS) impairs protein turnover and induce proteotoxic cardiac disease.Methods:In transgenic mice expressing constitutively active Nrf2 (caNrf2-TG) and non-transgenic controls (n=6/gp.), we examined the half-life and turnover rates of the myocardial proteome using D2O labeling and mass spectrometry.Results:We observed significant changes in the half-life of over 1,700 proteins, with approximately 1,200 proteins exhibiting increased half-life at 3 months, despite no noticeable defects in cardiac structure and function. Under OxS induced by isoproterenol (ISO), about 700 proteins showed reduced half-life, underscoring distinct regulatory mechanisms in protein turnover between cRS and OxS. Proteins with altered half-lives were involved in key cellular functions, including metabolism, signal transduction, immune response, transport, and cell cycle regulation under cRS, revealing novel targets undetected in an OxS context. Notably, distinct positive adaptive compensatory (59; p

Circulation, Volume 150, Issue Suppl_1, Page A4142098-A4142098, November 12, 2024. The anti-angiogenic impact of neutrophil elastase clouded the understanding of the role of neutrophils in promoting neovascularization (NV) and fibrinolysis in patients with chronic limb-threatening ischemia (CLTI). The impact of significant neutrophilia was not studied during clinical trials using Granulocyte Colony Stimulating Factor (G-CSF) to boost the deficient circulating endothelial progenitor cell count. Only recently have activated human neutrophils been documented to release pro-angiogenic factors such as VEGFA, Hepatocyte Growth Factor (HGF), MMP-9, angiopoietin (Ang1). They also stimulate and modulate fibrinolysis through release of proteases, and by promoting endothelial cell release of plasmin.The purpose of this abstract is to link clinical evidence* to these observations. Proteomic and cytometry data were obtained in 14 CLTI patients treated with Filgrastim 7-10 mcg/kg SQ every 72 h for up to a month. The absolute neutrophil count (ANC) increased a mean of 6-fold a day after each injection, returning to baseline within 72 hours. Significant (p < 0.05) increases in the concentration of VEGFA, HGF, MMP-9, Ang1 was measured by ELISA a day after both the 5th and the 10th Filgrastim doses as compared to baseline. The ANC peak was measured at the same time, as well as was the significant (p < 0.01) increases in the plasma concentration of plasmin ( >10-fold) and Fibrin Degradation Products (FDP) ( >5-fold). Since these patients also wore an infra-geniculate programmed compression pump (PCP) for 3 hours daily, these data were compared to 19 CLTI patients treated with PCP alone. PCP was used to improve the ischemic micro-environment and to provide endothelial shear stress as a strategy to induce arteriogenesis. PCP use did not influence the concentration of any of these proteins and did not induce neutrophilia. Resolution of ischemic rest pain and healing of ischemic ulcers contributed to limb salvage. Arterial hemodynamic improvement was supported by angiographic evidence of NV (enlarged corkscrew collaterals, improved contrast transit through the ischemic tissue). Segmental arterial recanalization indicated fibrinolysis. No hemorrhage occurred over the 30 day course. A prospective investigation of the uncovered link between neutrophilia, NV, and fibrinolysis is justified. * J Tissue Eng Regen Med. 2022 May;16(5):496-510. doi: 10.1002/term.3284

Circulation, Volume 150, Issue Suppl_1, Page A4139203-A4139203, November 12, 2024. Introduction:Spontaneous coronary artery dissection (SCAD) is a poorly understood cause of acute coronary syndrome (ACS), predominantly affecting young women and frequently related to acute stressors. It has been suggested that stress induced cardiomyopathy can cause dissection via mechanical distortion of the vessel at wall-motion hinge points. Whether specific coronary anatomic configurations also predispose to distortion and hence SCAD remains unknown.Hypothesis:Patients with left anterior descending (LAD) SCAD have a higher frequency of a “wrap around” (type IV – perfuses >25% of the inferior wall) LAD.Methods:Coronary angiograms of patients in the Mayo Clinic SCAD Registry were reviewed. Patients from functional angiogram registry with similar characteristics were used as controls. Patients with an LAD SCAD were compared to patients who never had an LAD SCAD. For identifying predictors of LAD SCAD, patients who never had an LAD SCAD were compared to patients that had an LAD SCAD as a recurrent event, but not as the initial presentation.Results:A total of 456 patients with SCAD (46±6 years; 96% women) were included. The control group consisted of 178 patients (44±7 years, 97% women). Type IV LAD was more common in the SCAD cohort (Figure 1), and patients in the LAD SCAD group had a higher proportion of type IV LAD when compared to non-LAD SCAD (47.6% vs 23.0% p < 0.001). Bifurcation involvement was also more frequent (48.6 vs 25.8%, p

Circulation, Volume 150, Issue Suppl_1, Page A4129182-A4129182, November 12, 2024. Introduction:Despite recent advances in therapy, chronic ischemic heart failure remains a significant cause of morbidity and mortality worldwide. Stem cell (SC) therapy has recently emerged as a potential therapeutic approach, yet its efficacy remains debatable. We aimed to systematically review and meta-analyze the current evidence to evaluate its effectiveness.Methods:A comprehensive literature search was conducted across the following databases: PubMed, Embase, and Cochrane, from inspection to April 2024. We identified RCTs with a blinded study design, done on patients diagnosed with chronic ischemic HFrEF, and utilized mesenchymal stem cells as an intervention in comparison to placebo/sham intervention using percutaneous endomyocardial catheter systems. Meta-analysis was conducted using RevMan v5.4 to calculate the odds ratio (OR) at 95% confidence intervals (CI) and a p-value of 0.05. I2was indicated for the assessment of heterogeneity. Sensitivity analysis was done in case of heterogeneity between studies.Results:A total of twenty studies were included in our meta-analysis. The overall change in left ventricular end-systolic volume (LVESV) and stress SPECT significantly favored the stem cell group (pooled effect size -7.59, 95% CI [-12.28 to -2.89], P=0.002), and (pooled effect size -5.33, 95% CI [-6.73 to -3.93], P=0.00001), respectively. Initially, the change in left ventricular end-diastolic volume (LVEDV) did not favor either group. However, sensitivity analysis which excluded one study at a time, reduced heterogeneity (P=0.01, I2=54%) and showed a significant effect favoring the stem cell group (pooled effect size -3.87, 95% CI [-6.77 to -0.97], P=0.009). However, the overall changes in left ventricular ejection fraction (LVEF) did not favor either of the two groups (pooled effect size 0.08, 95% CI [-0.1 to 0.26], P=0.39). Similarly, the overall change in myocardial oxygen consumption (MVO2) did not favor either group (pooled effect size 0.66, 95% CI [-0.1 to 1.32], P=0.05).Conclusion:Transendocardial SC therapy demonstrates promising results by significantly improving specific cardiac parameters. While the therapy shows potential, particularly after sensitivity adjustments, its impact on other critical measures like LVEF and MVO2 remains inconclusive. These findings highlight the need for further investigation to fully understand and enhance the therapeutic potential of stem cell interventions in heart failure management.

Circulation, Volume 150, Issue Suppl_1, Page A4142683-A4142683, November 12, 2024. Background:Pressure overload of the atria has been postulated to play a significant role in the development of atrial fibrillation. Piezo is a mechanosensitive channel protein and studies have revealed that piezo overexpressed in cardiomyocytes and fibroblasts can promote atrial fibrillation. However, whether pizeo is involved in cardiac ganglionated plexus and its role in atrial fibrillation remains unclear.Hypothesis:The aim of this study is to investigate whether piezo is expressed in the cardiac ganglionated plexus and plays an important role in atrial fibrillation.Methods:Cardiac ganglionated plexus were collected from 6 specimen with high left atrial pressure (high-LAP) or normal left atrial pressure (normal-LAP). Beagles were randomly allocated into sham group, AF group and piezo2-/- group. Atrial electrophysiological parameters, wov, left atrial pressure, neural function, neural activity and tissue of ganglionated plexus were detected.Results:Compared to the normal-LAP specimen, high-LAP resulted in an elevation of piezo2 in ganglionated plexus. RAP-induced increase in left atrial pressure promotes atrial fibrillation by overexpression of piezo2 increasing the function, activity, inflammation and oxidative stress levels of ganglionated plexus. Piezo2 -/- ameliorated atrial fibrillation susceptibility and showed a mild neuranagenesis. Moreover, notch signaling pathway maybe a significant mechanism.Conclusions:Piezo2-mediated mechanical transduction promotes atrial fibrillation by increasing ganglionated plexus activity and facilitating nerve regeneration, possibly through notch signaling.

Circulation, Volume 150, Issue Suppl_1, Page A4145256-A4145256, November 12, 2024. Introduction:Healthy urban environments are essential for improving cardiovascular health. Although exposure to wild green surroundings has been shown to have positive effects on mental and physical health, the effect of urban greenspaces on cardiovascular function and stress remain unclear.Research Question:Does being in an urban park decrease stress and autonomic tone as reflected by heart rate variability (HRV).Methods:We invited healthy adults (n=41; age 25-70 years) to participate in a cross-over panel study. They were randomly assigned to start in either a typical urban park or an adjacent urban space, spending 20min sitting and 20min walking. Self-reported distress and State-Trait Anxiety Index (STAI) scales were assessed before and after exposure. Pairedt-test was used to compare stress levels by site, and the effect size was calculated using regression analysis after adjusting for the level of starting distress. ECG recordings were acquired for the duration of the visit. HRV epochs of 5 min at the end of sitting or walking period and 40 min for the entire study were analyzed and compared using pairedt-test.Results:Pre-exposure distress and STAI summed scores were similar for the park and built spaces, but the level of distress was lower after visiting the park compared with built space (19.6±15.0 vs. 24.1±12.1; p=0.05). STAI scores were decreased after visiting the park, but not the built space (-5.4±8.2 vs. 0.8±6.8; p=0.003). When adjusted for the starting levels of distress, the summed STAI score after visiting the park was reduced by 6 (-10.34, -2.11), but no change for the built site. The standard deviation of NN intervals (SDNN) was higher in the park than the urban site (41.7 vs. 37.3; p=0.03) and the HR was lower (78 vs. 81; p=0.01) across the entire study epoch (40min). There was no significant change during the seated portion of visits, but across the walking portion, the values of SDNN were higher in greenspace (32.2 vs. 27.0; p= 0.01) and HR was lower (87 vs 84; p=0.02). Other HRV indices were not significantly affected.Conclusion:Visiting an urban park, but not a built environment, led to a decrease in self-reported distress, and a relative shift in the autonomic nervous system towards parasympathetic dominance. Although the relationship between changes in stress and HRV remain unclear, access to greenspaces may be an important factor in maintaining and enhancing cardiovascular health in urban environments.

Circulation, Volume 150, Issue Suppl_1, Page A4131424-A4131424, November 12, 2024. Introduction:Anomalous aortic origin of a coronary artery (AAOCA) can result in sudden cardiac death in the young and risk stratification is challenging. Though dobutamine stress cardiac MRI (DS-CMR) is feasible in pediatric patients, exercise stress CMR (ES-CMR) has lower rates of adverse events, higher diagnostic accuracy, and the ability to better reflect the physiologic changes occurring with exercise. No studies have evaluated ES-CMR in the pediatric population. We aim to describe our institution’s experience with ES-CMR using supine bicycle ergometry in patients with AAOCA.Methods:We retrospectively reviewed the medical records of AAOCA patients who underwent ES-CMR at our institution between 2011 and 2024 for demographic, clinical presentation, cardiopulmonary exercise test (CPET) and ES-CMR data. The exercise-based portion of the CMR consisted of supine cycle ergometry utilizing a ramp protocol, immediately after which perfusion imaging was performed. We used descriptive statistics for data analysis.Results:Of 38 patients who underwent ES-CMR, the median age was 16 years (range 13-24) and 68% were male. Diagnoses included anomalous right coronary artery (N=28), anomalous left coronary artery (N=8), and single coronary artery (N=1 single right, N=1 single left). Median maximal heart rate (HR) during ES-CMR was 160 bpm (range 130-190, median 80% predicted) with a median maximal HR during patients’ most recent CPET of 187 bpm (range 160-203, median 97% predicted). No patients had perfusion defects at rest or with exercise stress, or evidence of myocardial scarring. There were no adverse events.Discussion:We demonstrate for the first time the use of ES-CMR in a cohort of pediatric and young adult patients with AAOCA. ES-CMR can provide a unique modality to assess for ischemia at rest and stress as a means of risk stratification and simulate physiologic changes occurring with exercise stress in a single study. Although maximum heart rates during supine cycle ergometry are lower than those reached during CPET, they are similar to those reached during DS-CMR. ES-CMR can be a helpful and safe diagnostic tool in patients with AAOCA.

Circulation, Volume 150, Issue Suppl_1, Page A4116603-A4116603, November 12, 2024. Objective:Alarmins resulting from cell death or oxidative stress have been shown to be involved in the development of Kawasaki disease (KD) vasculitis. In our previous study, we demonstrated the potential role of (IL)-33 as an alarmin in the development of KD vasculitis. Although edematous dissociation (necrotic change) of the tunica media is thought to be a major source of IL-33 in KD vasculitis, it has not yet been elucidated.Methods:We investigated the impact of IL-33 released from necrotic human coronary artery smooth muscle cells (HCASMCs) on human coronary artery endothelial cells (HCAECs) by a co-culture assay using the Transwell®cell culture insert system. Subsequently, we evaluated the anti-inflammatory effects of anti-IL-33 and anti-ST2 antibodies compared to the conventional therapies of KD, such as high-dose IgG or anti-tumor necrosis factor (TNF)-α antibody.Results:Primary necrosis of HCASMCs induced significant release of IL-33. In co-cultures of necrotic HCASMCs with HCAECs, necrotic HCASMCs significantly induced the production of various proinflammatory cytokines in HCAECs. Anti-IL-33 and anti-ST2 antibodies exhibited unique inhibitory effects on the production of platelet-derived growth factor-BB or IL-12(p70) in HCAECs.Conclusion:The results of the present study suggest the potential involvement of edematous dissociation of the tunica media in the development of KD vasculitis. Furthermore, the distinctive anti-inflammatory effects of the anti-IL-33/ST2 axis drugs suggest novel therapeutic options for patients with refractory KD.

Circulation, Volume 150, Issue Suppl_1, Page A4147667-A4147667, November 12, 2024. The co-chaperone BAG3 is critical for protein quality control at the cardiac sarcomere. BAG3 binds to Hsp70 and coordinates the assembly of the CASA (chaperone-assisted selective autophagy) complex, thus supporting proteostasis and cardiomyocyte contractility. BAG3 mutations and/or decreased BAG3 levels are associated with cardiomyopathies, whereas BAG3 overexpression rescues ventricular function after myocardial infarction in mice. Despite BAG3’s promise as a therapeutic target, the mechanisms underlying BAG3 regulation are largely unresolved. Here, we investigate the mechanisms of BAG3 downregulation after stress. We found that BAG3 protein is reduced in human dilated cardiomyopathy hearts compared to non-failing hearts, yet there is an increase inbag3mRNA transcript, suggesting BAG3’s downregulation in heart disease may be controlled post-transcriptionally. To identify these post-transcriptional pathways, we subjected neonatal rat ventricular myocytes (NRVMs) to prolonged hypoxia-reoxygenation (H/R) stress, which recapitulated the decrease in BAG3 levels observed in human heart disease. Notably, disrupting Hsp70 binding to BAG3 in NRVMs via the drug JG-98 decreases BAG3’s half-life by ~90%, suggesting that Hsp70 protects BAG3 from degradation. Loss of Hsp70-mediated protection could contribute to declining BAG3 levels, so we quantified Hsp70 abundance after H/R stress in NRVMs, finding no significant change. We also found that overexpressing inducible Hsp70 did not rescue BAG3 levels. To examine BAG3 regulationin vivo,we subjected wildtype mice to ischemia-reperfusion injury. After 24 hours, male mice had no change in Hsp70 abundance in the left ventricle, whereas Hsp70 was significantly upregulated in female mice. Despite this difference in Hsp70, BAG3 levels were decreased by ~20% in both sexes. Thus, ourin vivoandin vitrodata both suggest that BAG3 downregulation is not caused by loss of Hsp70 binding/protection. Interestingly, the decline in full-length BAG3 (85 kDa) was accompanied by an increase in a BAG3 cleavage product at 74 kDa. We analyzed this product via mass spectrometry, discovering that it lacks a third of the WW domain, which is involved in autophagy. In future experiments, BAG3 cleavage will be explored as a potential mechanism of BAG3 loss. Such mechanisms will provide insight into how to maintain BAG3 levels, and thus cardiac function, during stress.

Circulation, Volume 150, Issue Suppl_1, Page A4139227-A4139227, November 12, 2024. Background:The treatment of secondary ischemic mitral regurgitation is challenging and predictors of functional and clinical outcome are pivotal in order to define the best therapeutic strategy. In these patients there is growing evidence that assessing the right ventricular (RV)-pulmonary arterial (PA) coupling during exercise has additive diagnostic and prognostic value.To date, no data are available as regard the exercise assessment of the RV- PA coupling in patients undergoing surgery for ischemic mitral regurgitationResearch Question:in patients with ischemic mitral regurgitation the evaluation of the exercise RV-PA coupling could play a crucial role for patients selection and prognosisAim:to test resting and exercise echocardiographic predictors of functional capacity and clinical outcome in patients referred to surgeryMethods:A 6-minute walking test and exercise stress echo performed at preoperative baseline, at 1 year and at median FU of 6 years (IQR: 3.70; range: 4.5– 8) on 50 patients (age: 67 ± 8 year; EF: 35 ± 5%), undergoing surgery by valve replacement or repair. Generalized linear mixed models were used to evaluate the predictive value of preoperative echocardiographic parameters on the longitudinal distribution of the 6-MWT.Results:Preoperative exercise tricuspid annular plane systolic excursion (TAPSE)/ pulmonary artery systolic pressure (PASP) ratio showed the strongest correlation with long-term six-minute walking test (r=0.81, p< 0.01) (Figure 1).The receiver operating characteristic analysis found that a preoperative exercise TAPSE/PASP < 0.34 predicted the lowest quartile of six-minute walking test at long-term (sensitivity: 79%; specificity: 100%) (Figure 2) and a composite clinical outcome of heart failure and death for any cause (PPV 91.3%, NPV 100%).On multivariable analysis TAPSE (Estimates:4.05; SE:0.90; p < 0.01) and TAPSE/PASP ratio (Estimates:106.9; SE: 31.54, p

Circulation, Volume 150, Issue Suppl_1, Page A4145417-A4145417, November 12, 2024. Introduction:Poor sleep is associated with adverse mental and cardiometabolic health outcomes. However, there are limited data on the interplay between insomnia and psychological distress domains and their influence on adiposity indicators among women.Aims:To evaluate associations of psychological distress domains with adiposity indicators and elucidate differences by insomnia status in a racially and ethnically diverse cohort of women.Hypothesis:We hypothesized that psychological distress would be associated with worse anthropometric indicators of adiposity and that insomnia would exacerbate these relations.Methods:This is a cross-sectional study of a community-based cohort of 237 women (69% racial/ethnic minority, 34.1±13.5y). Validated questionnaires assessed perceived stress (4-item Perceived Stress Scale), chronic stress (4-item Global Perceived Stress Scale), stressful life events exposure within the past year (8-item Life Events Checklist), and depression (2-item Patient Health Questionnaire). Insomnia was assessed using the validated Insomnia Severity Index, and BMI and waist circumference (WC) were measured by trained study personnel. Linear regression models adjusted for age and socioeconomic status examined associations of psychological distress with BMI and WC in the overall sample and by insomnia status.Results:There were no significant associations between psychological distress and anthropometric markers of adiposity in the overall sample. Although a statistically significant interaction between insomnia and stressful life events was observed (p-interaction0.05). Notably, associations of chronic stress with BMI varied by insomnia status (p-interaction=0.052). Specifically, higher chronic stress was associated with lower BMI (β=-1.55±0.72, p=0.044) among individuals with insomnia, but null results were observed among those without insomnia (β=0.07±0.16, p=0.66).Conclusions:Insomnia may moderate the association of stress with adiposity indicators. These findings highlight the complexity of the relations between sleep disorders, stress, and obesity risk and warrant replication in a larger sample and among males.

Circulation, Volume 150, Issue Suppl_1, Page A4145465-A4145465, November 12, 2024. Background:Myocardial bridging (MB) is a common congenital anomaly wherein a coronary artery segment takes an intramyocardial course. While often benign, MB may be associated with myocardial ischemia/stunning (MS), acute coronary syndromes (ACS), or even sudden cardiac death during periods of increased cardiac demand.Case presentation:A 47-year-old male with a history of type 1 diabetes mellitus was admitted to the Intensive Care Unit for diabetic ketoacidosis (DKA). He complained of epigastric pain with an electrocardiogram showing transient ST-elevation in the anterior and inferior leads. Cardiac troponin showed an upward trend with a peak of 0.202 ug/L and an elevated NT-proBNP of 5,014 pg/mL. A transthoracic echocardiogram (TTE) revealed left ventricular systolic dysfunction (LVEF 40%) with akinesis of the mid to apical anterior and septal walls, consistent with the left anterior descending (LAD) artery territory. Emergent left heart catheterization (LHC) revealed patent coronary arteries with severe mid-LAD MB with TIMI 3 flow. He was managed conservatively with guideline-directed medical therapy for heart failure, and subsequent TTE nine months later showed normalization of LV wall motion (LVEF 65%). Five months later, the patient was readmitted for DKA with elevated troponin. A repeat TTE demonstrated LV systolic dysfunction (LVEF 35%) with wall motion abnormalities (WMA) mirroring the initial presentation.Discussion:Our patient presented with recurrent episodes of ACS/MS complicated by LV systolic dysfunction along the LAD territory during periods of DKA, a known stressor for myocardial ischemia. The absence of obstructive coronary atherosclerosis on LHC, coupled with severe mid-LAD MB, suggests that the MB was the likely culprit for recurrent ACS/MS. Although stress cardiomyopathy was considered a differential diagnosis, this was less likely given the uncharacteristic pattern of WMA sparing the apical lateral and inferior walls as opposed to apical ballooning and the presence of an alternative diagnosis.Conclusion:This unique case underscores the importance of recognizing MB as a rare but potential cause of ACS/MS and LV dysfunction in patients with precipitating stressors such as DKA.

Circulation, Volume 150, Issue Suppl_1, Page A4142848-A4142848, November 12, 2024. Background:Post-translational histone modifications wield significant influence over cardiac hypertrophy and dysfunction. Apabetalone (APA), a selective inhibitor of BET proteins, effectively disrupts the interactions between bromodomain-containing protein 4 (BRD4) and chromatin, exerting modulation over transcriptional programs across various organs.Aim:We aim to investigate if APA could be beneficial in cardiometabolic heart failure with preserved ejection fraction (cHFpEF).Methods:Comprehensive assessments including histology, mouse echocardiography, and treadmill exhaustion tests were performed on mice subjected to high-fat diet and L-NAME for 15 weeks to induce cHFpEF. Unbiased gene expression profiling via PCR array and proteomics were conducted on left ventricular (LV) myocardial of HFpEF mice and control ones. Cultured cardiomyocytes (CMs) treated with palmitic acid (PA) served as an in vitro model of metabolic stress. cHFpEF mice received chronic treatment with APA (150mg/kg/day) or vehicle (DMSO). To bridge these findings to human relevance, passive stiffness of skinned CMs from cHFpEF patients was evaluated before and after APA treatment.Results:HFpEF mice exhibited notable characteristics including LV hypertrophy, diastolic dysfunction, myocardial fibrosis, lung congestion, and compromised exercise tolerance. APA treatment significantly ameliorated diastolic dysfunction, as evidenced by improvements in the E/A ratio and isovolumic relaxation time (IVRT), alongside a reduction in lung congestion, and enhancement in exercise tolerance. Transcriptomic analysis of PA-treated CMs and LV specimens of cHFpEF mice revealed a profound dysregulation of genes involved in inflammation, particularly IL-6, TNF-alpha, and IL-1beta. Chromatin immunoprecipitation assays demonstrated BRD4 occupancy on the promoters of various inflammatory genes, including IL6, with APA treatment resulting in the suppression of most inflammatory genes, notably impacting IL6 expression. APA led to a decrease in circulating levels of several inflammatory chemokines. The beneficial effects of APA were elucidated through the modulation of the IL-6/CaMKII/STAT3 pathway in both cHFpEF hearts and PA-treated CMs. Notably, in skinned CMs obtained from cHFpEF patients, both APA treatment and IL6 blockade exhibited a capacity to attenuate passive stiffness.Conclusions:Our findings set the stage for preclinical studies and exploratory clinical trials testing APA in patients with cHFpEF.