Risultati per: Lo stress può essere causa di infarto ed ictus

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Circulation, Volume 150, Issue Suppl_1, Page A4139170-A4139170, November 12, 2024. Background:Hypertrophic cardiomyopathy (HCM) is a global heart disease with great variability in disease severity, which can lead to significant impairment of exercise capacity. In healthy populations, oxygen consumption is related to cardiac output and arteriovenous oxygen difference. We sought to determine the relationship between hemodynamics (cardiac output and stroke volume) and oxygen consumption in HCM compared to healthy controls during maximal stress testing.Aims:To evaluate associations between the trajectories of hemodynamic function and oxygen consumption in HCM compared to healthy controls.Methods:Twenty individuals with HCM (51±15 years old, body mass index (BMI): 28±3 kg/m2, females, n=4) and 16 healthy controls (66±7 years old, 27±6 kg/m2, females, n=6) were included in the present study. Participants completed a maximal-graded stress test coupled with non-invasive hemodynamic bioreactance (cardiac output, stroke volume) and gas exchange (oxygen consumption, VO2) measurements. Data were analyzed in quartiles (exercise only) and phases (rest, pre-pedalling, exercise and recovery) of the maximal-graded stress test.Results:In HCM, cardiac output declined in the fourth quartile of the exercise phase of the stress test (-0.39 L/min,p

Circulation, Volume 150, Issue Suppl_1, Page A4114705-A4114705, November 12, 2024. Introduction:Stress Induced Cardiomyopathy is increasingly becoming more prevalent with increasing awareness about disease condition with annual incidence of 30 cases/100000 per year and an incidence of 1-2% in the patients presenting with acute coronary syndrome.[1] Physical and emotional triggers have been linked with occurrence of Stress induced Cardiomyopathy.Methods:We have obtained the National Readmission database for the year of 2020. We have used the ICD 10 code I51.81 for stress induced cardiomyopathy and found 10450 patients in the data base. Total 494 patients had cardiac arrest and 191 patients out of this 494 had died. We have used Binary logistic regression methods to find the odd ratio for physical and emotional risk factors for stress induced cardiomyopathy.Results:Grief disorder with an odd ratio of 7.2, followed by female gender with an odd ratio of 4.1, septic shock with an odd ratio of 3.3, Hemorrhagic stroke with an odd ratio of 1.73, ischemic stroke with an odd ratio of 1.72, depression with an odd ratio of 1.5, followed by asthma exacerbation with an odd ratio of 1.35 and seizure disorder with an odd ratio of 1.34 were among the few predictors for stress induced cardiomyopathy. Incidence of Cardiac Arrest was 4.7% and mortality rate of 1.8% was observed in the patients with stress induced Cardiomyopathy.Discussion:Extreme emotional and physical triggers like stroke, septic shock are among few significant risk factors for the stress induced cardiomyopathy.

Circulation, Volume 150, Issue Suppl_1, Page A4141446-A4141446, November 12, 2024. Emerging evidence suggests that vascular stress from cardiovascular-related co-morbidities promotes microvascular dysfunction, a key component in the development of heart failure with preserved ejection fraction. The sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin has been shown to reduce both morbidity and mortality associated with heart failure with preserved ejection fraction, however the full scope of influence of this therapy on human microvascular function remains unknown. We hypothesized that pre-treatment of isolated human microvessels with empagliflozin will prevent stress-induced endothelial dysfunction as evidenced by preserving both the magnitude of flow-induced dilation (FID) as well as the ability to dilate to nitric oxide. Human resistance arterioles (80-250µm) from healthy adults (defined as patients with ≤1 risk factor for cardiovascular disease) were dissected from discarded surgical adipose tissue and treated with empagliflozin (1µM), or vehicle control (ethanol) for 16-20 hours prior to the flow experiment. Vessels were cannulated for videomicroscopy and subjected to high intraluminal pressure (150mmHg, 30 min), an acute stress known to induce endothelial dysfunction. Vessels were pre-constricted with endothelin-1 prior to initiation of flow. A nonlinear logistic regression was used to determine differences between curves. Compared to vehicle control, vessels pre-treated with empagliflozin (1µM ) exhibited nitric oxide-dependent FID as dilation was impaired in the presence of the nitric oxide synthase inhibitor L-NAME (EC50 Control: 10.7 vs L-NAME 83.45, p=0.0107). This data suggests that empagliflozin, an SGLT2 inhibitor, promotes microvascular resilience to stress via preservation of nitric oxide-mediated FID. The ability to elicit stress resilience may explain in part some of the cardiovascular benefits associated with SGLT2 inhibitors and may offer unique opportunities for early intervention or prevention of microvascular dysfunction associated with comorbidities that contribute to heart failure with preserved ejection fraction.

Circulation, Volume 150, Issue Suppl_1, Page A4146301-A4146301, November 12, 2024. Background:Exercise stress testing uses metabolic equivalents of tasks (METs) to measure the energy cost of activities, aiding in the assessment of exercise capacity and cardiovascular health. Despite its significance, the correlation between calf muscle pump function (CPF) and exercise stress testing remains unexplored. We aimed to evaluate the relationship between CPF and peak METs as determined by cardiopulmonary treadmill exercise stress testing.Methods:The study included adults who underwent exercise cardiopulmonary stress testing and venous plethysmography at Mayo Clinic between April 2017 and March 2020. The protocols other than Bruce, Mayo, Modified Naughton, and Naughton protocols were excluded. The CPF ejection fraction (EF) was calculated per leg based on refill volumes post-exercise as a percentage of passive drain refill. The classification of CEAP (Clinical-Etiology-Anatomy-Pathophysiology) was utilized to better understand chronic venous insufficiency (CVI).Results:A total of 155 patients who underwent both exercise stress testing and venous plethysmography were included, with a mean age of 61.31 ± 14.03 years, and 84 (54.2%) were male. The peak measured METs for normal, unilaterally reduced, and bilaterally reduced CPF were 8.5 (2.5), 7.3 (2.1), and 7.1 (2.4), respectively (p=0.004, Figure 1). Multiple linear regression models were developed with METs as the outcome to determine if CPF was an independent predictor of METs on cardiopulmonary exercise stress testing. IIn model 1, the following independent variables were included: resting heart rate, peak heart rate, peak systolic blood pressure, recovery heart rate at minute 1, and worst EF (Table 1). In model 1, with only exercise parameters, lower EF was associated with lower METs (p=0.03). In a second analysis, variables identified as statistically significant with METs in the initial model were included, along with CEAP class (model 2) and CCI (model 3) (Table 2). In model 2, CEAP class 3 or higher was associated with decreased METs on the exercise stress test. This correlation implies that individuals with moderate to severe CVI may influence exercise capacity, demonstrating the interconnectedness of the cardiovascular system. Moreover, in model 3, the CCI, a predictor for mortality, was not significantly associated with METs.Conclusion:Our findings revealed that more severe CVI (CEAP class and reduced CPF) was associated with reduced exercise capacity after accounting for other factors.

Circulation, Volume 150, Issue Suppl_1, Page A4147602-A4147602, November 12, 2024. Coronary microvascular dysfunction (CMD), which is associated with diabetic cardiomyopathy, Takotsubo cardiomyopathy, andheart failure with preserved ejection fraction (HFpEF), is understudied. CMD is characterized by impaired endothelial-dependent vasodilation, but detailed mechanisms have yet to be elucidated.Nuclear Sirtuin 6 (SIRT6) plays essential roles in gene transcriptional, stress tolerance, DNA repair, inflammation, and aging. SIRT6 is strongly associated with cardiovascular pathologies, but how SIRT6 regulates endothelial metabolisms and homeostasis under metabolic stress and the underlying mechanism remains poorly understood. It might be because global Sirt6 knockout mice are perinatally lethal caused by hypoglycemia, suggesting the essential role of SIRT6 in glucose metabolism.In our preliminary studies, we generated inducible global Sirt6 knockout mice by crossing with Sirt6 f/f mice with CAG-cre (Sirt6f/f, CAG), and mice were viable with normal glucose levels. However, they showed impaired endothelial-dependent dilation (EDD) and impaired coronary flow reserve (CFR), an index clinically used to diagnose CMD. It suggests that deletion of Sirt6 might cause EC dysfunction because Sirt6 is reported to protect EC from premature senescence and oxidative stress by sustaining high eNOS levels. Surprisingly, when we studied non-inducible Sirt6 endothelial-specific knockout (Sirt6f/f, tie-2 cre) and inducible Sirt6 endothelial-specific knockout (Sirt6 f/f,Cdh5-cre/ERT2) and wild-type (WT) mice, Sirt6f/f, Tie-2and Sirt6f/f, Cadh5mice do not phenocopy the inducible global SIRT6 knockout mice, they had normal EDD and CFR. When the mice were fed a high fat and high sugar (HFHS) diet, the Sirt6f/f, Tie-2and Sirt6f/f, Cadh5had impaired EDD, suggesting Sirt 6 functioned differently in the mice fed with chow diet or HFHS diet.We hypothesize Sirt 6 deficiency causes coronary endothelial dysfunction and contributes to CMD; activating Sirt6 will ameliorate CMD. EDD was assessed using myography (DMT). Myocardial blood flow (MBF) was measured by Doppler. Our preliminary data show that the mediator of coronary vasodilation switched from NO to H2O2in the Sirt6 knockout mice with impaired EDD. Interestingly, when the mice fed on HFHS were treated with Sirt 6 activator MDL-800, the coronary microvascular function was improved, and the blood glucose level was decreased. The underlying mechanism and the pathways involved will be elucidated.

Circulation, Volume 150, Issue Suppl_1, Page A4140181-A4140181, November 12, 2024. Systemic hyperglycemia causes tissue damage and triggers cardiovascular disease (CVD). Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are a novel class of glucose-lowering agents that have shown unexpected benefits in clinical trials for the treatment of CVDs. We aim to investigate the underlying mechanisms of how SGLT-2 inhibitors alleviate CVDs associated with elevated glucose stress. iPSC-derived cardiomyocytes (iPSC-CM) were incubated with high glucose concentrations for 72 hours. Mitochondrial function in these cardiomyocytes was assessed by flow cytometry with JC-1 staining and ATP luminescence assay. Intracellular reactive oxygen species (ROS) and intramitochondrial calcium stress were measured using CellROX, MitoSOX, and Rhod-2 AM staining. Patch clamp was employed to determine ion current changes in the cardiomyocytes. Mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were determined using the Seahorse XFe96 analyzer. In addition, qPCR, Western blot, and DM mouse heart histological analysis were performed to assess the regulation of associated molecules. The results indicated that exposure to a high glucose environment caused cardiomyocyte injury and impaired mitochondrial biosynthesis. Empagliflozin exhibited a beneficial effect on mitochondrial function by reducing ROS production and calcium deposition. It also mitigated the reduction in respiratory OCR of cardiomyocytes induced by high glucose incubation. Furthermore, molecular analysis revealed that Empagliflozin attenuated the dysregulation of mitochondrial calcium channels and biosynthesis by reducing associated gene expression, includingBcl2,Mfn1,Mx2,Oas1,Ant3,Mcu,Micu1,Vdac1,Ryr2, andCypd-ppid. Histological analysis of DM mouse hearts demonstrated that reduced MFN2 and ZBP1 were target molecules for hyperglycemia-induced reduction of calcium channel currents in cardiomyocytes and could be restored by Empagliflozin treatment. This study concludes that high glucose stress diminishes mitochondrial calcium channel regulators MFN2 and ZBP1 in cardiomyocyte, which reduces calcium channel currents and leads to sensitization of cardiomyocyte to arrhythmogenesis, resulting in VT/VF. It provides experimental evidence for the clinical efficacy of Empagliflozin in ameliorating CVDs and managing diabetes-related CVDs.

Circulation, Volume 150, Issue Suppl_1, Page A4140185-A4140185, November 12, 2024. Introduction:Several studies have linked mental health disorders and substance abuse as risk factors for stress cardiomyopathy (SC). However, the true burden of these disorders amongst patients with stress cardiomyopathy remains unknown.Methods:We used the 2016-2020 National Inpatient Sample database to identify hospitalizations for SC who underwent diagnostic catheterization. We assessed the proportion of patients diagnosed with a substance abuse or mental health disorder. Subsequently, the association of these disorders in SC compared to patients admitted for myocardial infarction (MI) was assessed using the chi-square test.Results:From 2016 to 2020, there were 33,075 hospitalizations for stress cardiomyopathy who were diagnosed by cardiac catheterization. Of these patients, 5,920 (17.9 %) had depression, 8,500 (25.7 %) had anxiety, 1058 (3.2 %) had severe stress reactions, and 16,372 (49.5 %) were diagnosed with a mental health disorder. 9,955 (30.1 %) were smokers, 5,358 (16.2%) abused hallucinogens, 5,457 (16.5 %) abused cocaine, 5,457 (16.5%) abused sedatives, 6,019 (18.2 %) abused cannabis, 5,920 (17.9%) abused opioids, 6,416 (19.4 %) abused alcohol. Subsequently, the association of stress cardiomyopathy with mental and substance abuse disorder was compared with patients admitted with myocardial infarction See Table 1.Conclusion:Mental health and substance abuse disorders are common in patients diagnosed with SC. These disorders are more commonly present in SC compared to MI. Further research is needed to assess the significance of these findings.

Circulation, Volume 150, Issue Suppl_1, Page A4146754-A4146754, November 12, 2024. Background:Dobutamine stress echocardiography (DSE) is a frequently used tool in cardiovascular (CV) risk assessment of liver transplantation (LT) candidates. Its prognostic value compared to traditional cardiac risk stratification remains unclear.Research Question:How does the prognostic value of pre-transplant DSE in LT candidates compare to the revised cardiac risk index (RCRI)?Aim:Compare DSE’s prognostic value to RCRI in LT patients and analyze post-transplant CV outcomes.Methods:This single-center study included adult patients undergoing pre-transplant DSE as part of LT evaluation from 2008-2021. DSE were categorized as positive, negative, or inadequate. Primary outcomes were post-operative ischemic cardiac events and mortality, with secondary outcome of transplant delays from inadequate DSE. Mann-Whitney U and Fischer’s exact tests compared variables; logistic regression assessed RCRI and DSE for 30-day mortality and cardiac events.Results:Of 981 LT candidates, 644 (66%) had pre-transplant DSE with minimum 2-year follow-up. Average age was 57 ± 7 years, with 33% women. Four and eleven patients experienced cardiac events and mortality 1 (p-value 0.50), 0.51 for DSE (p-value 0.82), and 0.52 for RCRI >1 and DSE combined (p-value 0.80) in predicting 30-day mortality and cardiac events.Conclusion:Our study demonstrates limited prognostic value of DSE above RCRI score alone for predicting post-transplant mortality. Inadequate DSE was frequent and extended LT wait times. Further research is necessary to define clinically relevant subgroups and refine CV risk assessment in LT candidates.

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 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 A4142869-A4142869, November 12, 2024. Introduction:Adverse childhood experiences, also known as early life stress (ELS), are associated with increased risk of cardiovascular disease in later life, yet the underlying mechanisms remain elusive. Recent evidence indicates that parental life experiences can be transmitted to the offspring.Aim:To investigate the effects of ELS on cardiac structure and function in exposed parents and in their offspring, across 3 generations.Methods:We used ELS mouse model based on unpredictable separation of mouse pups (F1) from their mother (F0) each day for 3 hours from postnatal day 1 (PND1) to PND14 combined with dams exposure to an additional unpredictable stressor (forced swim in 18°C water for 5 minutes or 20-minute physical restraint in a tube) during separation. Control litters were raised normally. Echocardiography was performed at 6, 12 and 18 months in exposed animals (F0), their unexposed offspring (F1) and grand-offspring (F2). Both male and female mice were studied. Heart weight/tibia length was used to assess cardiac mass while Masson’s Trichrome was employed to detect fibrosis. Lung congestion was assessed as lung wet/dry weight ratio. Single-cell RNA sequencing (scRNAseq) was performed in MSUS and control hearts. A 6-week environmental enrichment (EE) program (cages containing running wheels, maze) was employed to test the possible rescue of ELS effects in adult males and their offspring.Results:F1 MSUS mice displayed increased LV mass, impaired diastolic function (assessed by conventional and tissue Doppler analysis) myocardial fibrosis and lung congestion. Time-dependent worsening of cardiac performance was observed from 6 to 18 months, both in males and females. ScRNAseq unveiled dysregulation of transcriptional programs underlying inflammation and lipotoxicity in the cardiomyocyte and endothelial cell clusters. MSUS offsprings did not show changes of cardiac function at 6 months, however diastolic dysfunction and lung congestion were observed at 12 and 18 months. A similar impairment of cardiac function was observed in the MSUS grandoffspring (F3). Of interest, 6-week exposure to an environmental enrichment protocol was able to improve LV mass, diastolic function and lung congestion in 12 months-old MSUS mice.Conclusions:ELS induces a transgenerational transmission of cardiac phenotypic alterations which can be rescued by EE. Our results shed light on the potential role of ELS on heart failure development and potential mitigation strategies.

Circulation, Volume 150, Issue Suppl_1, Page A4143635-A4143635, November 12, 2024. Background/Introduction:Delayed bedtime following stress disorder is prevalent in waves of pandemics and modern life. Considered to be a specific and important contributor to cardiovascular health, stress-related sleep disturbance has an unmet need in steady preclinical models. We previously found exciting corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVH) area of mice could induce 3-hour-long wakefulness.Methods:The chemogenetic method of designer receptors exclusively activated by designer drugs (DREADD) system was adopted to mimic stress-related sleep disturbance. We transfected PVH CRH neurons with rAAV-hSyn-DIO-hM3Dq-mCherry and rAAV-Crh-CRE. Prolonged CRH neuron activation was induced by daily intraperitoneal injection of clozapine N-oxide (CNO, 3mg/kg) at 9 am. Bulk RNA-sequencing and bioinformatics analysis were conducted for mechanistic exploration.Results:2-week repeated chemogenetic activation of PVH CRH neurons induced a 5-fold corticosterone release, consistent with increased daily 3-hour wakefulness and corresponding decreases in both rapid eye movement (REM) as well as non-REM sleep. Over 30% of chronic CRH activation mice displayed difficulties in maintaining balance and experienced premature mortality. Mice subjected to prolonged CRH activation showed impaired left ventricular ejection fraction (67.9% versus 48.2%, p=0.0011), and immune cell infiltration demonstrated by histological staining. Intriguingly, the number of circulating monocytes increased. Then, we performed bulk RNA-sequencing of heart and bone marrow from CRH-activated and control mice. Differential gene expression and gene set enrichment analysis (GSEA) indicated marked activation of interferon-beta-related pathways in both tissues. Cytosolic DNA-sensing pathway and related key effector genes (cGAS, Cxcl10, Ccl5) were found up-regulated in the heart, while the mitochondrial oxidative phosphorylation pathway was suppressed. We further adopted the CIBERSORT tool to estimate immune infiltration in heart tissues and characterized M1 macrophage as the main pro-inflammatory cell. In our stress-related sleep disturbance mouse model, macrophages in the heart and bone marrow shared similar properties inducing interferon-stimulated genes.Conclusion(s):Taken together, we report a failing heart in a mouse model of stress-related sleep disturbance. The neuro-immune axis involvement and molecular mechanisms merit in-depth explorations.

Circulation, Volume 150, Issue Suppl_1, Page A4145229-A4145229, November 12, 2024. Background:Stress-induced cardiomyopathy (CM) is a form of acute transient left ventricular dysfunction triggered by underlying physiological stress which often leads to increased morbidity and mortality. Coronavirus disease 2019 (COVID-19) is thought to cause stress-induced CM due to overwhelming systemic inflammation. There is paucity of data regarding the impact of COVID-19 on in-hospital outcomes of patients with stress-induced CM. The purpose of this study is to investigate in-hospital outcomes, including mortality and cardiogenic shock, of patients with concomitant COVID-19 and stress-induced CM.Methods:We queried the 2020 USA National Inpatient Sample (NIS) Database in conducting this retrospective cohort study. We identified hospitalized adult patients ≥ 18 years old with stress-induced CM and concomitant COVID-19 using ICD-10 CM codes. We used a survey multivariable logistic and linear regression analysis to calculate adjusted odds ratios (aORs) for outcomes of interest. A p value of