Risultati per: Demenze: trattamento farmacologico e non farmacologico e gestione dello stress del caregiver

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 A4125025-A4125025, November 12, 2024. Background:Chronic stress is associated with cardiovascular disease (CVD) in part through neural mechanisms that potentiate inflammation. Disrupted social connections are associated with higher chronic stress. As such, we hypothesized that: 1) previously married (divorced, separated) individuals have higher major adverse cardiovascular event (MACE) risk compared to married individuals and 2) that greater activation of stress-related neural-immune mechanisms contributes to this relationship.Methods:Participants (N=75,638) enrolled in the Mass General Brigham Biobank were studied. Marital status and MACE were identified using survey data and ICD-10 codes, respectively. A subset (N=1,121) underwent clinical18F-FDG-PET imaging, enabling assessment of stress-related neural activity as the ratio of the amygdala to prefrontal cortex activity (AmygAc). Clinical high-sensitivity C-reactive protein (hs-CRP) levels were assessed in another subset of the cohort (N=10,358). Linear and Cox regression and mediation analyses were used.Results:Among participants (median age 62 years; 53% female), 2,978 subjects developed MACE after Biobank enrollment. Previously married (vs. currently married) individuals had greater MACE risk (HR 1.33 [95% CI: 1.20,1.57], p=

Circulation, Volume 150, Issue Suppl_1, Page A4141274-A4141274, November 12, 2024. Background:Atherosclerosis is the most common cause of cardiovascular death. Oxidative stress is related to the initiation and progression of atherosclerosis. However, how oxidative stress affects the progression of atherosclerosis in vivo has not yet been fully investigated. Non-obstructive general angioscopy (NOGA) can meticulously visualize directly aortic atherosclerosis in vivo. The purpose of this study was to evaluate the relationships between oxidative stress and NOGA-derived aortic plaques.Methods:We investigated 120 consecutive cases with coronary artery disease evaluated for the aorta by NOGA between July 2021 and February 2024. Atherosclerotic lesions of the aorta were screened using NOGA immediately after coronary arteriography. NOGA examination evaluated the counts of ruptured plaques, chandelier signs, intense yellow plaques, and red thrombi in the aorta. Regarding the number of each plaque, we assessed the proportion of aortic findings detected by NOGA at each vertebral level. Derivatives of reactive oxygen metabolites (d-ROMs) levels as indices of reactive oxygen species production were evaluated.Results:The mean age was 66 years, and the median d-ROM value was 289 U.CARR [interquartile range: 251-339]. The d-ROM value was significantly correlated with the proportion of ruptured plaques (r=0.28, p=0.015), but not correlated with the other plaque characteristics. In a multiple linear regression analysis for the proportion of ruptured plaques in the aorta, d-ROMs were one of the independent factors adjusted for age, sex, hypertension, dyslipidemia, and diabetes mellitus (β=0.14, p=0.004).Conclusion:The value of d-ROMs was related to the proportion of ruptured plaques in the aorta, but not to the proportion of the other plaque characteristics. Oxidative stress may help to elucidate the mechanism for the progression of aortic atherosclerosis.

Circulation, Volume 150, Issue Suppl_1, Page A4145622-A4145622, November 12, 2024. Introduction:Endothelial cells (ECs) can improve blood perfusion in diseased blood vessels associated with peripheral artery disease, but direct injection of therapeutic cells significantly decreases their survival and functionality for angiogenesis. To address these limitations, we employed a class of mechanically tunable protein hydrogels to enhance the survival and angiogenic behavior of human induced pluripotent stem cell-derived ECs (iPSC-ECs).Hypothesis:We hypothesize that the optimal stress relaxing mechanical property of hydrogels will modulate iPSC-EC survival and function in a mouse model of hindlimb ischemia.Materials&Methods:Engineered hydrogels, termed elastin-like protein (ELP)-polyethylene glycol (PEG), consists of two components of a hydrazine-modified elastin-like protein (ELP-HYD) and an aldehyde- or benzaldehyde-modified, polyethylene glycol (PEG-ALD or PEG-BZA), which interact with each other through hydrazone dynamic covalent chemistry bonds to form ELP-PEG hydrogels. By varying the use of PEG-ALD or PEG-BZA, we created hydrogels with the same stiffness but at either fast or slow stress relaxation rates. The hydrogels were assessed by dynamic oscillatory rheology. Afterwards, 106human iPSC-ECs were encapsulated within gels and injected into a mouse limb ischemia model to assess transplant cell viability and the ability to restore vascular perfusion to the ischemic limb.Results and Discussion:Although both hydrogels had a Young’s Modulus of 500 Pa, the stress relaxation rate of the PEG-BZA was 2.5h (slow), whereas that of PEG-ALD was within minutes (fast). When the iPSC-ECs were injected into the ischemic limb within either fast or slow-relaxing hydrogels or in saline, bioluminescence imaging of the luciferase-tagged iPSC-ECs showed higher cell survival within the fast-relaxing hydrogel over the course of the first 7 days. Blood perfusion recovery by laser Doppler similarly showed higher mean perfusion ratio when cells were delivered in the fast-relaxing hydrogel.Conclusions:ELP/PEG-ALD promotes iPSC-EC cell survival and perfusion recovery in the ischemic limb.

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 A4143744-A4143744, November 12, 2024. Introduction/Background:Hypertension and hypercholesterolemia are important risk factors of endothelial dysfunction and atherosclerosis. Previous studies suggested a crosstalk between an activated renin-angiotensin-aldosterone system (RAAS), reactive oxygen species (ROS) and oxidized low-density lipoproteins (oxLDL) in atherosclerosis, but the underlying molecular mechanisms are not well understood.Research Question/Hypothesis:Can we identify novel signaling pathways controlling the molecular crosstalk of the RAAS with ROS and oxLDL in endothelial dysfunction and atherosclerosis?Methods/Approach:The impact of AT1R blockade on oxLDL-induced superoxide anion formation and endothelial dysfunction was studied in human umbilical artery endothelial cells and aortic rings of wild-type mice by chemiluminescence and Mulvany myograph. We cloned 5’-terminal deletions of the AT1R promoter and assessed the luciferase activity in human endothelial cells. Oct-1 binding to the human AT1R promoter region was studied by EMSA. Further assays included real-time PCR, confocal microscopy, Western blotting, G protein reporter assays, phospho-ERK1/2 antibodies and specific siRNAs. The data were validated in heart of obese C57BL/6 mice and cardiac and aortic tissue of AT1a/AT1bdouble knockout micein vivo.Results/Data:AT1R promoter activation studies upon Ang II- and oxLDL-stimulation in endothelial cells revealed that Ang II and oxLDL activate AT1R signaling through G protein Gα12/13, followed by activation of ERK1/2 MAP kinases, and transcription and translation of Oct-1, resulting in up-regulation of AT1R, LOX-1 and NOX2 expression, which could be antagonized by specific inhibitors at each step of the identified signaling cascade. AT1R blockade improved oxLDL-induced endothelial dysfunction in aortic rings of wild-type mice. Male C57BL/6 mice fed a high-fat diet exhibited upregulation of Oct-1 levels in cardiac tissues, compared to normal controls, while AT1a/AT1bdouble knockout mice demonstrated downregulation of Oct-1, AT1R, LOX-1, and NOX2 on mRNA and protein level in cardiac and aorta tissue, thus confirming the identified signaling cascadein vivo.Conclusions:Oct-1 is an essential transcription factor for Ang II- and oxLDL-induced upregulation of AT1R and LOX-1 expression in endothelium, thus identifying a novel molecular cross-talk of oxLDL with ROS signaling and the RAAS contributing to development of endothelial dysfunction and atherosclerosis.

Circulation, Volume 150, Issue Suppl_1, Page A4144014-A4144014, November 12, 2024. Introduction:Lower socioeconomic status (SES) associates with greater MACE risk in part via stress-related mechanisms. Further, a higher polygenic risk score for neuroticism (nPRS), a marker linked to stress sensitivity and chronic stress conditions, is associated with greater MACE risk. Moreover, individuals with higher nPRS are more susceptible to the cardiovascular impacts of lower SES. Yet, it remains unknown whether individuals with higher nPRS experience greater adverse changes in autonomic and inflammatory intermediaries of stress in the setting of lower SES and whether these changes contribute to MACE risk. Accordingly, we tested the hypotheses that: 1) lower SES links to MACE risk via lower heart rate variability (HRV) and higher C-reactive protein (CRP), and 2) lower SES has a greater impact on HRV and CRP among those with higher nPRS.Methods:Individuals (N=18093; median age 64 years; 54% female) with nPRS and SES data were identified in the Mass General Brigham Biobank. SES was assessed as the median income of an individual’s residential zip code with lower income defined as the lowest tertile. Higher nPRS was defined as values ≥ population median. MACE data was collected for 10 years following enrollment using ICD-10 codes. CRP (N=4117) and HRV (N=4412) data were collected from available clinical lab values and electrocardiograms, respectively, with HRV assessed as the standard deviation of all normal RR intervals.Results:In the full cohort, both HRV and CRP mediated the relationship between lower SES and MACE risk (p

Circulation, Volume 150, Issue Suppl_1, Page A4137935-A4137935, November 12, 2024. Background:We have recently reported that repetitive cardiac decompensation with multimorbidity often experienced by patients with heart failure (HF) is attributed to epigenetic modifications of hematopoietic stem cells (HSCs) in the bone marrow (BM). HF reprogrammed HSCs differentiation and altered tissue macrophage homeostasis. These findings demonstrate that the BM can carry an innate immune memory of cardiac stress that may exacerbate HF and predispose other organs to pathology.Aims:Because the stemness of HSCs is mainly regulated by mesenchymal stromal cells (MSCs) in the BM niche, we investigated phenotypic alterations of MSCs under cardiac stress.Methods&Results:Transcriptome analysis of MSCs showed preferential differentiation toward adipocytes in murine pressure overload models.In vitroassays and histological BM sections also support this finding. Furthermore, single-cell RNA sequencing of MSCs demonstrated that the percentage of adipocyte-primed MSCs increased in proportion to the severity of cardiac dysfunction, and also correlated with the frequency of myeloid-lineage progenitor cells. To investigate the influence of adipo-lineage MSCs on HSCs, we conducted BM transplantation supplemented with MSCs from control or HF mice. Recipient mice transplanted with HF-MSCs showed significant increases in myeloid-biased multipotent progenitors in BM and myeloid cells in peripheral blood. Additionally, the number of proinflammatory cardiac macrophages was significantly increased in the HF-MSCs group, promoting cardiac fibrosis and dysfunction.Conclusions:Our results demonstrated that the BM niche could perceive cardiac stress in the form of adipocytic skewing of MSCs in the setting of HF, which changed the differentiation behavior in HSCs and ultimately led to further deterioration of cardiac function through the impaired differentiation of circulating monocytes into cardiac macrophages. Therefore, suppressing the adipocytic differentiation of MSCs could have a novel therapeutic potential to avoid repeated HF events.

Circulation, Volume 150, Issue Suppl_1, Page A4144217-A4144217, November 12, 2024. Background:The ISCHEMIA trial questioned revascularization in chronic coronary syndrome (CCS) patients, but excluding subjects with left main (LM) coronary artery disease (CAD). A widely available diagnostic method excluding LMCAD would expand the implementation of an initial noninvasive strategy.Objective:Assessing the ability of excluding LMCAD through clinical and ECG stress testing (EST) variables in patients undergoing coronary angiography (CAG) for CCS.Methods:In a multicenter retrospective case-control study we evaluated CCS subjects undergoing CAG after a maximal EST.Caseswere patients with angiographic ≥50% LM stenosis or ≥70% stenoses of both proximal left anterior descending and proximal circumflex arteries; we matched them with similar patients without LMCAD (Controls)in a 1:3 ratio. Models were internally validated through logistic regressions.Results:219Caseswere matched with 554Controls. The c-statistic was 0.80 (optimism-adjusted: 0.73). Assuming LMCAD prevalence of 5% and a misclassification cost ratio of 1:100 (ratio of the cost of performing CAG in a subject without LMCAD to the cost of not performing CAG in a patient with LMCAD), the negative predictive value was 98.6%, correctly classifying 84.5% ofCases. CAG could be spared in 57.0% of subjects, missing one LMCAD diagnosis every 70 CAGs spared in patients without LMCAD (Figure).Conclusions:Among patients with CCS, LMCAD can be predicted withacceptablediagnostic accuracy anda very highnegative predictive value through a model based on clinical and EST parameters, allowing an initial noninvasive management of most patients able to perform an EST, reducing the costs of routine coronary imaging. Such results should enlarge the applicability of the ISCHEMIA results when coronary computed tomography angiography, used in ISCHEMIA, is not available, limiting the referral to invasive CAG.

Circulation, Volume 150, Issue Suppl_1, Page A4142206-A4142206, November 12, 2024. Background:To apply human pluripotent stem cell-derived endothelial cells (hPSC-ECs) in regenerative medicine, exploring methods for highly purified ECs is desirable. Cell sorting is a versatile technique for isolating and purifying specific cell types, yet mechanical cell loss persists. Previously, we established a differentiation method for human induced pluripotent stem cell-derived ECs (hiPSC-ECs) based on lineage control using vascular endothelial growth factor (VEGF) and 8-Bromo cyclic adenosine monophosphate (cAMP). However, achieving high hiPSC-ECs purity without cell sorting has not yet been possible.Hypothesis:We speculated that applying digital rocker-generated shear stress during a specific period of hiPSC-EC induction would yield highly purified hiPSC-ECs without cell sorting.Methods:We applied cyclic share stress to the cultured cells using a digital rocker. To optimize the frequency and duration of digital rocker application, ECs purity on day 13 of differentiation (d13) was analyzed by flow cytometry for vascular endothelial cadherin (VE-Cadherin). Shear stress was measured using a simulation model. The functionality of ECs was evaluated through reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) for endothelial nitric oxide synthase (eNOS) and angiogenesis assay.Results:The optimized protocol consisted of a rocking period from day 5 (representing the EC progenitor stage) to d13, at 30 cycles/min with 13° tilt (equivalent to 1.09 dyn/cm2), which significantly increased the purity of ECs (Control vs Rocking: VE-Cadherin; 69.25±17.43 vs 86.68±6.023 %, P = 0.0090). Examining the number of cells on d13 revealed rocking stimulation reduced both ECs and non-ECs. Non-ECs were nearly absent, suggesting EC purification occurs by removing non-ECs, indicating ECs are more resistant to being eliminated by the rocking stimulation. The rocking culture also led to increased eNOS mRNA expression on d13 (Control vs Rocking: 0.5574±0.4985 vs 1.056±0.1652, P = 0.0393). The angiogenesis assay showed a longer vascular structure length trend in the rocking group, indicating enhanced angiogenic capacity. (Control vs Rocking: 15407±2929 vs 18335±3568 Pixel, P= 0.4309).Conclusion:In this study, we developed a method where digital rocker-generated shear stress during a specific period of hiPSC-EC induction not only selectively purifies ECs without cell sorting, but also enhances endothelial function, demonstrating their therapeutic potential.

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 A4140852-A4140852, November 12, 2024. Introduction:Posttraumatic stress disorder (PTSD) is an independent cardiovascular disease (CVD) risk factor with high prevalence in women, particularly women veterans (WV). While the impact of PTSD on ischemic heart disease (IHD) and stroke has been well established, its impact on a comprehensive set of CVD outcomes has not been studied in WV, a growing population at high risk for CVD in the U.S. The goal of this project was to investigate the impact of PTSD on a comprehensive set of CVD conditions in WV.Methods:National Veterans Health Affairs (VHA) electronic health records were used to identify all women who visited any VAs from 1/1/2000 to 12/31/2019. PTSD and CVD were identified based on International Classification of Disease versions 9 and 10 diagnoses ( 1 inpatient or 2 outpatient encounter documentations). Incident CVD outcomes included first onset of IHD, stroke, cardiomyopathy/heart failure (HF), pulmonary arterial hypertension/pulmonary hypertension (PH), atrial flutter/fibrillation (AF), peripheral arterial disease (PAD), venous thromboembolism (VTE), and aortic stenosis (AS). Propensity score matching and Cox survival analyses were performed to assess associations of PTSD with incident CVD outcomes.Results:We identified 622,312 WV, with 140,210 (22.53%) with PTSD. After 1:1 matching, 202,896 patients were included in the final analysis. WV had a mean age of 39.1 years, and the mean [MOU1] follow-up was 5.72 years. Table 1 reveals the association of PTSD with an incident CVD composite and the different component outcomes individually.Conclusion:In a large sample of WV, we demonstrate significant and clinically relevant associations of PTSD with a comprehensive set of incident CVD outcomes. The potential association with some of the specific outcomes warrant further investigation. Maybe more of a call to action for PTSD screening and treatment to potentially offset CVD risk instead?

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 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 A4138303-A4138303, November 12, 2024. Background:A higher stress hyperglycemic ratio (SHR) has been reported to be associated with adverse cardiac outcomes. However, the role of SHR in predicting clinical outcomes by comparing patients with and without diabetes mellitus is yet to be explored.Objective:To evaluate the prognostic value of the SHR for predicting major adverse cardiovascular (MACE) and all-cause mortality in ACS patients with and without diabetes mellitus.Methods:Per PRISMA guidelines, we comprehensively reviewed PubMed, Google Scholar, and SCOPUS for eligible studies reporting on SHR and its association with MACE (8 studies) and all-cause mortality (7 studies) in ACS patients. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a binary random-effects model, with results displayed as forest plots. Heterogeneity was assessed using I2 statistics, and a leave-one-out sensitivity analysis was performed. P

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