Risultati per: Come stress e attacchi di cuore sono collegati

Circulation, Volume 146, Issue Suppl_1, Page A14447-A14447, November 8, 2022. Introduction:Quantitative myocardial blood flow (MBF) analysis using stress cardiac magnetic resonance (CMR) has been shown to detect obstructive coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) in several mostly small, single-center studies. The AQUA-MBF (Assessment ofQUAntitativeMBF) study is a multicenter initiative involving 16 centers.Hypothesis:The goal of this sub-study is to determine if MBF can differentiate CAD, CMD, and normal volunteers in this multicenter setting.Methods:We present data from 53 subjects (15 with CAD, 20 at risk for CMD and 18 controls) who underwent vasodilator stress CMR (Figure) using 1.5T and 3.0T MR scanners (General Electric). At risk for CMD was defined as having diabetes and 2 other risk factors in absence of ≥50% stenosis based on coronary CT. CAD was defined as the presence of stenosis ≥70% based on invasive coronary angiography. Stress perfusion images were acquired using the dual sequence technique. Stress MBF was measured in each of the 16 AHA segments using Fermi deconvolution (Circle Cvi42). In the CAD group, each segment was further classified as having late gadolinium enhancement (LGE), supplied by CAD, or a normal remote territory. The means of the 5 groups were compared using one-way analysis of variance.Results:The segmental stress MBF (ml/g/min) for the 5 groups are shown in figure. Compared to the normal group, segmental stress MBF in 4 disease groups were significantly lower (p

Circulation, Volume 146, Issue Suppl_1, Page A15067-A15067, November 8, 2022. Introduction:Ischemia with non-obstructive coronary arteries (INOCA) is a relatively new condition, often observed in patients with angina. However, the exact pathophysiology of INOCA is not fully understood, and its management remains very debated.Hypothesis:We hypothesized that admission hyperglycemia in INOCA patients could be associated with the risk of being re-hospitalized for chest pain.Methods:We evaluated INOCA patients referred to our Institution between 2016 and 2021 for percutaneous coronary intervention (PCI). We divided our population in quintiles according to the values of the stress hyperglycemia ratio (SHR), calculated as the ratio of admission blood glucose (expressed as mmol/L) and HB1Ac (%). We calculated Kaplan-Meier product limits for cumulative ratio of reaching the endpoint and we applied the log-rank test. To further confirm our results, we performed a multivariable analysis in order to adjust for potential confounders.Results:2874 INOCA patients were enrolled in our study. At 1-year follow-up, the risk of hospitalization for chest pain was progressively higher in patients with higher SHR values (p

Circulation, Volume 146, Issue Suppl_1, Page A13105-A13105, November 8, 2022. Introduction:Pulmonary arterial hypertension (PAH) is a rare fatal disease with vascular remodeling leading to increased right ventricular pressure followed by fibrosis. To study PAH-induced cardiac fibrosis we develop anin vitromodel of the failing right ventricle, for which cardiac fibroblasts (cFBs) were generated from healthy subjects’ and PAH patients’ induced pluripotent stem cells (iPSC).Methods:Confluent iPSC were induced to differentiate by adding 12 μM CHIR99021 for 24h to RPMI supplemented with B27 without insulin. Next, cells recovered for 24 h in RPMI supplemented with B27 without insulin, followed by stimulation with 75 ng/ml FGF2 up to day 20. Finally, the differentiated cells were reseeded and submitted to 10% cyclic stretch at 1 Hz for 4 days using the Flexcell FX-6000 system. Control and PAH cFBs were characterized at gene and protein levels.Results:The differentiated cells had a spindle morphology typical of FBs. Furthermore, the presence of cardiac (GATA4, TCF21) and fibroblast (VIM, PDGFRα, COL1A1) markers at gene and protein levels confirmed the cFB identity. Comparable expression of fibroblast related genes was observed in PAH cFBs as well as controls. Over 4 weeks of culture, iPSC-cFBs increasingly expressed markers of activated FBs (ACTA2andPOSTN)over time, similar to in vitro adult cFBs. When exposed to mechanical stretch, cell aligned to the stretch direction. Surprisingly, no increase in gene expression of extracellular matrix (COL1A1, COL3A1) or activated fibroblasts (ACTA2, POSTN) markers was observed.Interestingly, under static and stretch conditions expression of these genes was increased in PAH cFBs compared to healthy cells.Conclusion:The cellular morphology after differentiation as well as the gene and protein analyses indicate that cFBs were successfully generated. Furthermore, cyclic stretch induced alignment of the cells but was not sufficient to stimulate fibroblast activation in either PAH or healthy cFBs.

Circulation, Volume 146, Issue Suppl_1, Page A14807-A14807, November 8, 2022. Introduction:Stress-induced cardiomyopathy (SIC) is a form of transient non-ischemic cardiomyopathy that is precipitated in the setting of acute emotional or physical stress. Postulated hypothesis implicated catecholaminergic excess and a role of the brain-heart axis behind its pathogenesis. The impact of different psychiatric illnesses on the outcomes of SIC is not clear.Method:We conducted a retrospective study using National Readmission Database (NRD) from 2011 to 2019 using ICD-10-CM (International Classification of Diseases, 10th Edition, Clinical Modification) and ICD-9-CM codes to identify the admissions with the discharge diagnosis of SIC and stratified them based on the presence of psychiatric illnesses. The primary outcome was six-month readmission and predictors of readmission.Result:We included a total of 98,721 admissions with a diagnosis of SIC. Among them, 12.9% had major depression, 1.8% had bipolar disorder, 17.6% had an anxiety disorder, and 0.6% had schizophrenia. Overall, patients with psychiatric illnesses were younger. Patients with psychiatric illnesses had a higher burden of comorbidities. Patients with schizophrenia had higher in-hospital mortality. Patients with psychiatric illnesses had a higher likelihood of getting readmitted within six months (p

Circulation, Volume 146, Issue Suppl_1, Page A9504-A9504, November 8, 2022. Introduction:The pathobiological mechanisms of coronary plaque erosion are unclear. Low endothelial shear stress (ESS) is a proinflammatory/proatherogenic stimulus associated with coronary plaque progression/destabilization. Intravascular imaging studies suggest that high ESS gradient (low ESS areas adjacent to high ESS areas), and steepness of plaque upslope/downslope correlate with plaque erosion. We investigated the relationship of local fluid hemodynamics to the inflammatory microenvironment at the culprit site of erosion in patients with an acute coronary syndrome.Hypothesis:ESS metrics associate with proinflammatory/proatherogenic cells and cytokines, and contribute to plaque erosion.Methods:We studied 30 patients with erosion from the OPTIcal-COherence Tomography in Acute Coronary Syndrome study (OPTICO-ACS). OCT images were segmented, co-registered with the angiogram to create a 3D-reconstruction of the coronary artery. ESS metrics were calculated by Computational Fluid Dynamics. Systemic and local blood samples and thrombectomy specimens were collected at the culprit lesion and analyzed by flow cytometry-based immunophenotyping and plasma cytokine and chemokine profiling, and statistically tested for correlations of continuous variables using Spearman rank correlation (r).Results:Proinflammatory cytokines (IL6, MIP-1, IL1β, IL2) and local concentration of T-cells, including subsets of T-cells (CD4+, CD8+, and NKT-cells), were significantly higher at the culprit site of erosion and correlate with local adverse ESS metrics (Min ESS, Max ESS, Plaque Topographical Slope) (Table).Conclusion:Biomechanical features likely trigger activation of the adaptive immune system, including T-lymphocytes and their cytotoxic effector molecules. These results provide novel insights into the links between fluid hemodynamics, inflammatory activation, and mechanisms involved in the pathogenesis of coronary plaque erosion.

Circulation, Volume 146, Issue Suppl_1, Page A14748-A14748, November 8, 2022. Introduction:Chronic stress conditions associate with a greater incidence of hypertension (HTN).Hypothesis:We tested whether genetic risk for or neurobiological features of vulnerability to chronic stress associate with the risk for and timing of HTN.Methods:Data were obtained from Mass General Brigham Biobank participants. HTN was defined as >2 International Classification of Disease codes at least one week apart. Those with secondary HTN and those diagnosed at age

Circulation, Volume 146, Issue Suppl_1, Page A9608-A9608, November 8, 2022. Background:Recent evidence highlights oxidative stress as an important mechanism to cardiac dysfunction in type 2 diabetes (T2D) and altered β3-adrenergic receptor (AR)-activated nitric oxide synthase (NOS) pathway contributing to this process. However, the NOS isoforms involved are controversial. The mechanism of how β3-AR stimulation impacts ROS, SERCA2a, and cardiac function in T2D is unclear. We tested the hypothesis that oxidant stress from upregulation of LV β3-AR-activated iNOS uncoupling promotes T2D cardiomyopathy.Methods:We compared myocyte β1- and β3-AR, NOS, peroxynitrite (NT), NADPH and SERCA2a expressions and myocyte functional responses to β- and β3-AR stimulation with isoproterenol (ISO,10-8M) and BRL-37344 (BRL,10-8M), respectively, in the absence and presence of iNOS inhibitor, 1400W (10-5M) of female mice over 14 weeks (W): 7 normal and 7 with T2D induced by 14 W high-fat diet (HFD) intake, but after HFD for 4 W receiving streptozotocin (STZ, 40 mg/kg/day, i.p. 5 days).Results:Versus normal myocytes, T2D myocytes had significantly increased protein levels of β3-AR (0.25 vs 0.14) and iNOS (0.25 vs 0.15) accompanied with increased oxidative stress indicated by significantly-elevated NT formation, NADPH (P67-phox, 33% and p22-phox, 29%) and decreased GTPCH expression (0.43 vs 0.85) and activity. T2D myocytes had significantly decreased β1-AR (0.35 vs 0.49) and SERCA2a (0.19 vs 0.29). These changes were associated with reduced cell contraction (dL/dtmax, 75.4 vs 133.7 μm/s), relaxation (dR/dtmax, 59.6 vs 113.8 μ m/s), and [Ca2+]iT(0.16 vs 0.21) accompanied by diminished β-AR-stimulated positive inotropic response, but enhanced β3-AR-induced negative inotropic response. Only in T2D myocytes, pretreatment with 1400W improved basal cell function and augmented ISO-increased dL/dtmax(64.5%) and [Ca2+]iT(29.2%), but significantly limited BRL-induced decrease in dL/dtmax(12.7%) and [Ca2+]iT(9.8%).Conclusions:T2D is associated with contrasting changes on myocyte β1- and β3-AR expression with decreased SERCA2a and increased iNOS. Upregulation of β3-AR triggers iNOS uncoupling, leading to oxidative stress, thus promoting intrinsic myocyte dysfunction with impaired [Ca2+]iregulation and reduced β-AR reserve.

Circulation, Volume 146, Issue Suppl_1, Page A13332-A13332, November 8, 2022. Introduction:Stress Cardiomyopathy (SCM), is an acute reversible myocardial injury associated with transient left ventricular dysfunction. Risk factors include female sex, post-menopause, anxiety, depression, schizophrenia, asthma and chronic obstructive pulmonary disease, diabetes, and substance use. Obesity has an increased sympathetic tone and state of chronic metabolic stress, both of which are similar in etiology to SCM. We postulate that obesity may have high prevalence in patients with SCM.Methods:We queried the Nationwide Inpatient Sample database (2016-2019) to identify adult patients with SCM with and without obesity, along with other common co-morbidities using ICD-10 codes. We compared the categorical and continuous variables by Pearson χ2 and Student t test.Results:There were 31,725 patients with SCM. The mean age was 67.15+14 years and the population was predominately female, n=26409 (83.2%). Racial distribution consisted of White (n=24713 77.9%), Black (n=24713, 8%), and Hispanic (n=1918, 6%). There were 3816 (12%) who were diagnosed with obesity. When comparing both groups, obese patients were found to be younger than non-obese, 63.3+14 years vs. 67.68+13 years, p

Circulation, Volume 146, Issue Suppl_1, Page A11734-A11734, November 8, 2022. Introduction:Chest pain is common in patients with Post-acute Sequelae of SARS-CoV-2 (PASC), also known as long COVID, but the mechanism is unknown.Hypothesis:We hypothesized that PASC patients with chest pain have impaired myocardial perfusion reserve (MPR) measured by stress perfusion cardiovascular magnetic resonance (CMR) imaging.Methods:We retrospectively identified the first 30 consecutive patients who underwent clinically ordered adenosine stress perfusion CMR for chest pain persisting >4 weeks after SARS-CoV-2 infection (PASC). Patients with a history of coronary artery disease (CAD) or left ventricular ejection fraction (LVEF) 2 SD below mean MPR for controls.Results:In 30 PASC (67% female, age 43±13) and 13 controls (54% female, age 50±12), with LVEF (61±6% vs 59±8%), native T1 (1001±49 vs 992±57 ms), T2 (49.5±3.7 vs 48.0±3.3 ms), and ECV (24.6±2.9 vs 24.6±2.6%) were similar (p >0.2 for all). Prior pericarditis (n=2) or prior myocarditis (n=3) were infrequent, with no acute disease by CMR. PASC patients had significantly lower global MPR than controls (1.54±0.25 vs. 2.20±0.36, p

Circulation, Volume 146, Issue Suppl_1, Page A13379-A13379, November 8, 2022. Background:Cardiovascular disease (CVD) is highly prevalent among older persons with HIV (OPWH) occurring on average a decade earlier than non-infected individuals largely due to chronic inflammation, vascular pathology, and psychosocial stressors. Effective cardiovascular risk reduction strategies such as exercise have been shown to lower both physiological and psychosocial stressors but have not been widely reported in the HIV population.Objective:To evaluate the effect of a one-year, moderate intensity aerobic exercise intervention on perceived stress among OPWH with ≥ 2 CVD risk factors.Methods:A secondary analysis was performed utilizing data from Project FiTBRAiN, a 2-arm RCT that included Let’s Move (moderate intensity aerobic exercise intervention) or Let’s Flex (flexibility/stretching attention control) groups. The 14-item Perceived Stress Scale (PSS) was utilized to measure participants’ perceived stress. Data analysis included an analysis of variance with pairwise and between-group differences reported.Results:Participants (n=115) reported a mean age of 55±5.2, and the majority were African American (n=100, 87.0%) and male (n=66, 57.4%). The most common cardiovascular comorbidities were elevated: total cholesterol (n=114, 99.1%), systolic blood pressure (n=108, 93.9%), diastolic blood pressure (n=98, 85.2%), and participants had a mean BMI of 28.29. Baseline 14-item PSS scores for the Let’s Move Program and Let’s Flex Program were 19.49 (SD=7.94) and 21.13 (SD=8.64), respectively, indicating moderate stress levels. Over all time points, the control group (Let’s Flex) had higher perceived stress than the intervention group (Let’s Move), but were not significant.Conclusions:Our findings suggest that moderate levels of psychological stress were present in this population and may be a risk factor for CVD among OPWH. The consistent finding that perceived stress remained lower over time indicates that aerobic exercise may be beneficial for stress reduction. Additional research is needed to determine the optimal dose and mode of exercise that is most beneficial for stress reduction in this population.

Circulation, Volume 146, Issue Suppl_1, Page A11394-A11394, November 8, 2022. Introduction:Chest pain is a common presentation in the emergency department and physician office visits. Identifying coronary artery disease (CAD) as the cause of chest pain is essential for improving prognosis. The 2021 AHA/ACC guidelines do not advocate for testing in patients with low pretest probability (PTP

Circulation, Volume 146, Issue Suppl_1, Page A11736-A11736, November 8, 2022. Background:Parents of infants born with congenital heart disease (CHD) are at increased risk for mental health problems, including anxiety, depression, and post-traumatic stress (PTS). Few studies have examined to what extent the hospital experience influences these mental health symptoms over time. The purpose of this pilot study was to determine hospital factors predicting parent anxiety, depression, and PTS at 3 months post-discharge.Methods:A convenience sample of 28 biological mother-father dyads was enrolled consecutively from August 2018 to October 2019 from one children’s hospital in the Northeast, US. Parents were instructed to complete questionnaires, including valid and reliable instruments for mental health symptoms, within one week of their infant’s surgery and 3 months post discharge. Associations between hospital factors and each mental health symptom at 3 months post discharge were assessed using linear mixed effects models, accounting for the anticipated correlation between parents of the same infant using an unstructured covariance matrix. Separate linear mixed effects models were constructed for each mental health symptom using backward selection method.Results:For each one unit increase in parental role alteration, anxiety symptoms were estimated to be increased by 5.98 (SE+1.60; p=0.002). Parents with at least a college education were estimated to have greater anxiety symptoms compared to parents with high school/technical school or less (10.89+3.75; p=0.009). For each one unit increase in role alteration, depressive symptoms were estimated to be increased (4.41+1.72; p=0.02). PTS was also significantly predicted by role alteration (5.06+1.91; p=0.02) along with timing of CHD diagnosis, with postnatal diagnosis estimated to increase PTS symptoms by 21.80 (SE+10.07; p=0.04) units compared to prenatal diagnosis.Conclusion:Role alteration experienced by parents during their infant’s hospitalization significantly predicts anxiety, depression, and PTS symptoms 3-months after discharge. Additional factors were identified that can inform mental health screening in this population. Future interventions to enhance the role of parents during infant hospitalization may support parent mental health post discharge.

Circulation, Volume 146, Issue Suppl_1, Page A14699-A14699, November 8, 2022. Introduction and Hypothesis:Endothelial shear stress (ESS) is the tangential force produced by luminal blood flow on arterial endothelium. Both high ESS and low ESS are known to have atherogenic effects, however, it remains poorly understood how these different forces influence coronary atherosclerosis. We evaluated the impact of ESS changes on biochemical and phenotypic difference of coronary atheroma, as assessed by a novel dual-modal optical coherence tomography-fluorescence lifetime imaging (OCT-FLIm)in vivoin beating human coronary arteries.Methods and Results:We constructed a fully-integrated OCT and multispectral FLIm system based on a low-profile dual-modal imaging catheter. High-speed OCT-FLIm could be performed safely in patients undergoing coronary revascularization (Pullback speed: 10-20mm/sec). 3D artery model for computational fluid dynamics was reconstructed by fusion of OCT and angiography. We analyzed spatial associations between ESS and multispectral FLIm information: ch.3(542nm) = fibroatheroma with inflammation; ch.1 (390nm) = loose fibrous tissue (healed plaque). OCT-FLIm visualized coronary microstructure clearly and offered correctly-coregistered biochemical readouts of coronary atherosclerotic plaquein vivoin a label-free manner. Fibroatheromas with increased inflammation activity, as assessed by ch.3 FLIm, were found in low ESS area. On the other hands, high ESS area colocalized with regions with increased ch.1 lifetime, a FLIm signature of loose fibrous tissue (healed plaque). Based on a coregistered ESS-FLIm data, we found a statistically significant negative correlation between ESS and ch.3 lifetime (p >0.001) and a positive correlation between ESS and ch.1 lifetime (p >0.001).Conclusions:Low ESS was associated with lipid and macrophage infiltration whereas high ESS was associated with presence of loose fibrous tissue, a histologic marker of recent plaque disruption leading to rapid plaque progression. Our novel imaging strategy enabling comprehensive evaluation of complex interaction between ESS and biochemical phenotype of plaques is expected to enhance understanding of coronary atherosclerosis biology.

Circulation, Volume 146, Issue Suppl_1, Page A11502-A11502, November 8, 2022. Background -Mitral valve prolapse (MVP) is a common valvular abnormality found in approximately 2.4% of the population. Whereas the majority of cases are benign, an increasingly recognized sequela of MVP is sudden cardiac death (SCD), but triggers and risk factors for SCD are not well-defined. It is theorized that increased stretch on the papillary muscles due to MVP leads to papillary muscle fibrosis and cellular changes of local conduction properties, increasing the risk of ventricular arrhythmias and SCD.Hypothesis- We hypothesized that patients with MVP and SCD would have increased ventricular arrhythmias and ECG changes compared to MVP controls during exercise stress testing.Methods -The study population was generated from the Duke Epic. Patients were included if they had guideline-based diagnosis of MVP on echocardiogram or cardiac magnetic resonance imaging. Increase in ventricular arrhythmias during exercise was defined as >/= 10 PVCs per minute, multifocal PVCs, or >/= 2 PVCs in a row.Results-A total 2,513 patients with MVP were screened. 18 patients with SCD. Patients with SCD were younger [(47.22 +/- 12.2 ) vs. (58.0 +/- 18.7), p=0.02], more likely to be female (89.9% vs 64%, p=0.04) and had increased rate of bileaflet prolapse (72% vs. 40%, p=0.01) compared to controls. Patients with sudden cardiac death had either dynamic T wave changes or increased ventricular arrhythmias with stress testing versus controls [12/18 (66.7%) vs 17/75 (22.6%), p

Circulation, Volume 146, Issue Suppl_1, Page A14532-A14532, November 8, 2022. Introduction:Severe COVID-19 infection is known to alter myocardial perfusion through its effects on the endothelium and microvasculature. However, a significant proportion of the world population suffered from only mild COVID-19 symptoms, and it is unknown if their myocardial perfusion is altered following their recovery.Hypothesis:In this study, we aimed to determine if there are detectable abnormalities to myocardial perfusion using cardiac magnetic resonance (CMR) in individuals who have recovered from mild COVID-19 infection.Methods:We conducted a prospective, comparative study of individuals who have recovered from COVID-19 infection (n=33) and risk-factor matched controls (n=27) using regadenoson stress CMR by a 1.5T MR scanner (GE Signa Artist) (figure). Quantitative stress perfusion images were acquired using the dual sequence technique. MBF was measured during rest (rMBF) and stress (sMBF) using Cvi42 software(figure). Myocardial perfusion reserve (MPR) was calculated as sMBF/rMBF. Unpairedttest or the Mann-Whitney U test was used to test differences between the two groups.Results:The median time interval between COVID-19 infection and CMR was 6 (4, 9) months. 31/33 (94%) patients in COVID-19 infection were not hospitalized. Symptoms including chest pain, shortness of breath, syncope, and palpitations were greater in COVID-19 group than in the matched controls (19/33 (58%) vs 2/27 (7%), p

Circulation, Volume 146, Issue Suppl_1, Page A10270-A10270, November 8, 2022. Introduction:Computational modeling studies indicated that pathological high shear stress (HSS) of 100 dynes/cm2is generated in pulmonary arteries (PA) (100-500μM) in patients with a ventricular septal defect or idiopathic pulmonary arterial hypertension (PAH) and occlusive vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is a feature of PAH.Hypothesis:Pathological HSS induces EndMT, which contributes to the initiation and progression of PAH.Methods:We applythe Ibidi perfusion system to human PA endothelial cells (EC), to determine whether HSS (100 dynes/cm2) induces EndMT, when compared to normal laminar shear stress (LSS) (15 dynes/cm2). We assessed the mechanism and targeted it to prevent PAH in a mouse with HSS resulting from an aortocaval (AV) shunt.Results:HSS induced EndMT, as assessed by an increase in transcription factors, SNAI1 and SNAI2, reduced BMPR2 (previously shown to inhibit EndMT), decreased EC markers PECAM1 and CDH5, and increased mesenchymal markers, ACTA2 and FSP-1. While the flow-induced transcription factors, KLF2 and KLF4 were similar in LSS and HSS, the co-transcription factor ERG was reduced with HSS. IndeedERGsiRNA under LSS caused EndMT whereas under HSS, transfection ofERGprevented EndMT. To address the significance of our observations in an animal model we created an AV shunt in mice and compared PAH in those sham operated vs transfected with an adeno-associated viral (AAV2- ESGHGYF) vector selectively targeting PAEC with aluciferase(control) or anERGexpressing construct (N=10 per group). Eight weeks after AV shunt, right ventricular systolic pressures was 21.9 ±0.6 mmHg in sham, 37.2±1.0 mmHg in AV shunt with luciferase vector (p