Risultati per: Incontinenza urinaria da stress o mista

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 A12676-A12676, November 8, 2022. Backgrounds:Psychological stress increases leukocyte accumulation within atherosclerotic lesions and exacerbates plaque vulnerability. However, the stress-induced real-time behavior of immune cells in the atheroma has been poorly definedin vivo. Here, we aim to investigate whether stress stimulates the inflammatory leukocyte dynamics in the atherosclerotic plaques and destabilizes the lesions using customizedin vivocell tracking strategies.Methods and Results:We developed a system and motion reconstruction algorithm that can probe and compensate for respiratory and pulsatile movements. Individual leukocytes near the atherosclerotic plaques were imaged in real-time by adapting a custom-built high-speed intravital microscopy system with multiple fluorescence channels. Stress was achieved by immobilization procedures and/or stereotaxic application of stress stimulus onto the brain amygdala. The high spatial and temporal resolution of our real-time cell tracking system allowed clear identification of rhodamine 6G-positive leukocytesin vivo. In the common femoral artery bifurcation of apolipoprotein E knockout mice, white blood cells firmly adhered to the inner layer of the vessel walls while some slowly flowed along the endothelium (Figure). We further demonstrate that the stress increased the rolling and adhesion of inflammatory leukocyte subsets near the atherosclerotic lesions, and enhanced the plaque macrophage activity as assessed byin vivoimaging. Confocal laser scanning microscopy and immunostaining analyses corroborated thein vivofindings that the stress induced the destabilization of the atherosclerotic plaques.Conclusion:Our data show that stress stimulated the dynamics of inflammatory leukocyte subsets in atherosclerotic environments and increased the plaque vulnerability as assessed by the customized high-resolution motion-compensatedin vivoimaging strategy.

Circulation, Volume 146, Issue Suppl_1, Page A13149-A13149, November 8, 2022. Introduction:Hemodynamic responses to mental stress (MS) have been associated with adverse CV outcomes. We investigated if hemodynamic responses during laboratory MS testing are predictive of outcomes.Hypothesis:Lower rate pressure product (RPP) changes during MS testing are predictive of adverse CV events.Methods:Patients recruited into the Mental Stress Ischemia Prognosis Study and Myocardial Infarction and Mental Stress Study 2 studies underwent MS testing with a standardized public speaking stressor and followed for incident CV death, MI rates (primary endpoint) and heart failure hospitalizations (secondary endpoint). Maximum changes in the RPP during MS were calculated. A generalized linear mixed model determined predictors of RPP change, and Prentice, Williams, Peterson model gap time approach was used for analysis of recurrent events after adjustment for demographic and clinical variables.Results:In 919 patients (mean 59.6 years; 65.6% men), the median change in RPP was 5,112 mmHg x beats/minute (IQR, 3,666 – 7,120). Patients with lower RPP changes (

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 A13293-A13293, November 8, 2022. IntroductionTakotsubo cardiomyopathy (TCM) is a recognized reversible process associated with emotional or physical stressors characterized by left ventricular apical ballooning in the absence of obstructive coronary artery disease. We present a unique case of TCM after albuterol use in the setting of hyperthyroidism.ResultsA 74-year-old woman with history of hyperthyroidism and asthma presented with acute substernal chest pain and progressive dyspnea. She was diagnosed with an asthma exacerbation, started oral prednisone 3 days before presentation, and reported using 16 puffs of her albuterol inhaler the day before. Examination revealed blood pressure 157/100 mmHg, heart rate 135 beats per minute, respiratory rate of 35 breaths per minute, and SpO2 94% on a 5-liter nasal cannula. Lung exam revealed bilateral end-expiratory wheezes, and she appeared in respiratory distress. The remainder of the exam was unremarkable, including cardiac exam. ECG revealed atrial tachycardia with ST elevations in the anterolateral leads concerning for injury. High sensitivity troponin was 1484 ng/L (ref

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 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 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 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 A13208-A13208, November 8, 2022. Introduction:Posttraumatic stress disorder (PTSD) is associated with increased risk of ischemic heart disease (IHD). It is unclear if this excess risk is entirely mediated through traditional IHD risk factors (hyperlipidemia, hypertension, diabetes, and smoking). We examined 13 potential mediators of the PTSD-IHD association in a large cohort of women veterans: traditional risk factors, other conditions (obesity, chronic kidney disease, neuroendocrine disorders), women-specific risk factors (e.g., gestational diabetes and hypertension, pre-eclampsia), and psychiatric disorders (depression, anxiety, psychotic disorders, alcohol dependence, and drug dependence).Methods:The study cohort included women veterans ≥18 years of age who were enrolled in Veterans Health Administration care between 1/1/2000 to12/31/2017. Diagnosis of each risk factor and disorder was based on administrative billing codes (International Classification of Disease versions 9 and 10). The final study cohorts included 1:2 propensity-score matched group of patients with and without PTSD respectively. The cohorts were matched for age, number of prior visits, and presence of the above risk factors. Cox regression examined associations of PTSD with time to development of the above 13 risk factors. Cox regression with time-varying covariates was used to model time to development of IHD as a function of PTSD and each of above 13 risk factors as time-varying predictors in separate models.Results:The cohorts included 132,293 patients with, and 265,846 patients without PTSD. PTSD was positively associated with each of the 13 risk factors. Results are tabulated in the table below.Conclusion: Traditional risk factors cumulatively accounted for just one third of the risk of IHD posed by PTSD, and all examined risk factors accounted for less than half of the increased risk associated with PTSD. More research is needed to identify pathways by which PTSD accelerates cardiovascular risk.

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 A15081-A15081, November 8, 2022. Introduction:In the Fontan (FN) circulation pulmonary blood flow (Qp) is passive, resulting in severely decreased shear rate and velocity in pulmonary arteries to the point of stasis. Yield stress (YS) is the shear stress required for blood to transition from stasis to a moving fluid. Therefore, YS may be a determinant of Qp in FN. We evaluated YS in patients with FN and Glenn (GLN) circulations and whether increased YS is associated with decreased Qp.Methods:We enrolled 20 patients with biventricular (2V) congenital heart disease (CHD) and 41 patients with single ventricle CHD (19 FN and 22 GLN) who were undergoing a clinically indicated cardiac catheterization. Two patients were excluded due to pulmonary vascular disease. We obtained blood samples at the time of catheterization and measured blood viscosity across shear rates 1 s-1to 1000 s-1using a Rheolog viscometer We calculated YS by curve-fitting of the viscosity measurements to a Casson fluid model.Hypothesis:We hypothesize that higher yield stress will be associated with lower pulmonary blood flow in Fontan circulation.Results:The FN group was the oldest and had the largest BSA (FN >2V >GLN; pFN >2V; p

Circulation, Volume 146, Issue Suppl_1, Page A10199-A10199, November 8, 2022. Introduction:For Marfan syndrome patients (MFS) with thoracic aortic aneurysms (TAA), prosthetic graft surgery provides lifesaving benefits, but adverse event risk persists in the native aorta for which mechanism is unclear. Sustained impact of proximal grafts on biomechanics within and distal to grafts is unknown.Methods:MFS patients with chronic ( > 6 month) proximal grafts were compared to non-surgical MFS (nsMFS) and age/sex matched controls: Wall shear stress (WSS) on 4D flow cardiac MRI and size (diameter) were quantified at aortic landmarks (ascending, arch, descending, thoracoabdominal).Results:34 subjects were studied including MFS late (7.3±6.7 years) after graft implantation (n=12). Post-surgical MFS were of similar age (p=0.93) and sex (p=0.64) to controls but older than non-surgical MFS (45±10 vs 33±11 yo, p=0.01): In the ascending aorta (grafted territory), post-surgical MFS had higher WSS (1.17±0.55 Pa) than nsMFS (0.74±0.17 Pa) and controls (0.60±0.17 Pa; p=0.002 for trend). Similarly, in the (native) descending aorta, WSS was higher in post-surgical (1.06±0.24 Pa) than nsMFS (0.97±0.11) and controls (0.83±0.16; p=0.02) (Figure) paralleling results in the arch (p=0.06) and a similar trend in the thoracoabdominal aorta (p=0.12). Among the overall MFS cohort (n=23), proximal graft implantation associated with increased WSS in the ascending and descending aorta (both p

Circulation, Volume 146, Issue Suppl_1, Page A12929-A12929, November 8, 2022. Introduction:Posttraumatic stress disorder (PTSD) has been associated with ischemic heart disease in women veterans. To date, the evidence for the potential association of PTSD with other cardiovascular disorders remains limited. Furthermore, the overwhelming majority of the research in this area has been conducted predominately in men. The goal of this investigation was to evaluate the association of PTSD with incident stroke in a large cohort of women veterans.Methods:Veterans Affairs (VA) electronic health records were used to identify women veterans aged ≥18 years who visited any VAs nationwide from 1/1/2000-12/31/2017. Diagnosis of each risk factor and disorder was based on administrative billing codes (International Classification of Disease versions 9 and 10). The final study cohorts included 1:2 matched group of patients with and without PTSD respectively. The cohorts were matched for age, traditional risk factors such as diabetes, hypertension, hyperlipidemia and smoking, as well as obesity, chronic kidney disease, psychiatric disorders (depression, anxiety), female specific risk factors (e.g., pre-eclampsia), drug and alcohol dependence, neuroendocrine disorders (e.g., hypo or hyperthyroidism), and number of visits. Cox regression was used to model incident stroke as a function of PTSD.Results:The study population included 398,769 patients, including 132,293 with PTSD and 265,846 matched patients without PTSD. The cox regression analysis revealed that PTSD was significantly associated with greater rates of incident stroke (hazard ratio [HR]=1.64, 95% confidence interval: 1.43-1.86, p

Circulation, Volume 146, Issue Suppl_1, Page A15165-A15165, November 8, 2022. Introduction:Guidelines recommend the use of Dobutamine stress echocardiography (DSE) in case of low flow low gradient aortic stenosis (LFLG AS) when left ventricular ejection fraction (LVEF)

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.