Search Results for: Incontinenza urinaria da stress o mista

Circulation, Volume 150, Issue Suppl_1, Page A4147087-A4147087, November 12, 2024. Introduction:Fractional flow reserve (FFR) is an invasive, lesion-specific surrogate for myocardial ischemia. The use of FFR to guide lesion selection for revascularization has been shown to improve outcomes compared to an angiographic approach because it allows revascularization of lesions based on hemodynamic significance.Purpose:To compare the outcomes of patients randomized to the invasive (INV) arm of the ISCHEMIA trial who underwent FFR during initial angiography with those whose treatment was guided by angiography alone.Methods:The ISCHEMIA data set was obtained from the NHLBI. Subjects randomized to the INV arm who underwent FFR were compared to those who underwent angiography alone. Unadjusted cumulative event probabilities were estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards analysis was used to estimate the independent impact of FFR on outcomes. Primary endpoint of interest was cardiovascular death (CV) death or MI.Results:Of the 5,179 patients with chronic coronary syndromes and at least moderate ischemia on stress testing, 2,588 were randomized to the INV strategy, 2,475 underwent angiography and 2,210 had baseline data available for analysis. Of these, 410 (19%) had FFR performed during diagnostic angiograms. Females comprised 24% of FFR patients and 24% of non-FFR patients (P=0.85). FFR patients were older than non-FFR patients (65.7 [8.7] years vs. 64.3 [9.6] years, P=0.006). The incidence of hypertension, diabetes, smoking, or prior MI at baseline did not differ between groups. Fewer FFR patients had severe ischemia at baseline (45% vs. 52%) and more had mild or moderate ischemia (54% vs. 48%) (P=0.009). FFR patients had less extensive disease as manifested by fewer native vessels with >70% stenosis than non-FFR patients (1.0 [0.9] vs. 1.5 [1.0], P

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

Circulation, Volume 150, Issue Suppl_1, Page A4146347-A4146347, November 12, 2024. Background:Acute ischemic stroke (AIS) is a leading cause of mortality and disability globally, disproportionately affecting Black and Latinx populations who experience increased morbidity and mortality compared to their white counterparts. At one month, roughly 50% of AIS survivors experience mood disturbances (e.g., anger, irritability, and aggression) and exhibit a lower health-related quality of life (HRQOL) compared to pre-AIS levels. Downstream biomarkers of mitochondrial dysfunction such as oxidative stress may be important pathophysiological mechanisms underlying mood disturbance symptoms, stroke severity, and long-term functional recovery.Purpose:To examine associations among early and late peripheral plasma lipid levels, mood disturbance symptoms (e.g., anger, irritability), and HRQOL outcome over 3 months (baseline/study day 5, and months 1, 3) in persons following AIS.Methods:The pilot study is a non-probability, convenience sample of adult subjects ( > 18 years of age) with a diagnosis of AIS. Lipidomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS) of untargeted lipids. The Agilent 6545 LC/Q-TOF platform was used to determine the absolute concentration of lipid species from peripheral plasma samples collected days 1, 3, 5 and months 1 and 3 post-AIS. General linear mixed models were used to test the predictive association of lipidomic biomarker mean value of peripheral plasma lipid levels and symptoms and outcomes over time (baseline and months 1 and 3).Results:We analyzed 82 subjects (age = 64 ± 12.1, 52% male, 78% Black, and 94% with hypertension). Elevated oxidative stress biomarkers (e.g., lipoxygenases, arachidonic acid, glycosylphosphatidylinositol) were associated with higher severity of anger and irritability symptoms, and a poorer HRQOL from baseline to 1- and 3-months post-AIS (p=0.04).Conclusion:An untargeted LC-MS lipidomics approach was used to identify lipids following AIS. Because oxidative stress plays a key regulatory role in complex downstream cellular function, these findings may be of great significance in understanding AIS pathophysiology that has the potential to inform personalized preventive strategies.

Circulation, Volume 150, Issue Suppl_1, Page A4141686-A4141686, November 12, 2024. Chronic inflammation and tissue fibrosis are common stress responses that worsen organ function, yet the molecular mechanisms governing their crosstalk are poorly understood. In diseased organs, stress-induced changes in gene expression fuel maladaptive cell state transitions and pathological interaction between diverse cellular compartments. Although chronic fibroblast activation worsens dysfunction in the lung, liver, kidney, and heart, and exacerbates many cancers, the stress-sensing mechanisms initiating the transcriptional activation of fibroblasts are not well understood. Here, we show that conditional deletion of the transcription co-activatorBrd4in infiltratingCx3cr1-positive myeloid cells ameliorates heart failure and is associated with a dramatic reduction in fibroblast activation. Analysis of single-cell chromatin accessibility and BRD4 occupancyin vivoinCx3cr1-positive cells identified a large enhancer proximal toInterleukin-1 beta(Il1b), and a series of CRISPR deletions revealed the precise stress-dependent regulatory element that controls expression ofIl1bin disease. Secreted IL1B functioned non-cell autonomously to activate a p65/RELA-dependent enhancer near the transcription factorMEOX1, resulting in a profibrotic response in human cardiac fibroblasts.In vivo, antibody-mediated IL1B neutralization improved cardiac function and tissue fibrosis in heart failure. Mechanistically, systemic IL1B inhibition or targetedIl1bdeletion inCx3cr1-positive cells prevented stress-induced expression ofMEOX1and inhibited fibroblast activation. The elucidation of BRD4-dependent crosstalk between a specific immune cell subset and fibroblasts through IL1B provides mechanistic insights into how inflammation drives profibrotic cell states and presents new therapeutic strategies for heart disease and other chronic inflammatory disorders featuring maladaptive tissue remodeling.

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

Circulation, Volume 150, Issue Suppl_1, Page 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 A4143303-A4143303, November 12, 2024. Introduction:Preeclampsia is a hypertensive disorder of pregnancy associated with cardiovascular disease. Systemic peripartum microvascular alternations have been implicated in pregnancies complicated by preeclampsia. Whether coronary microvascular dysfunction is a potential mediator of preeclampsia-associated cardiovascular risk is unknown. We aimed to determine whether individuals with a history of preeclampsia have coronary microvascular dysfunction measured by cardiac magnetic resonance imaging (CMR) at least 5 years postpartum.Methods:Women with singleton pregnancies complicated by preeclampsia and a comparator group with uncomplicated, normotensive deliveries were identified and prospectively enrolled to undergo regadenoson stress perfusion CMR (1.5T Signa Artist GE HealthCare) at least 5 years postpartum. Using the dual sequence technique, fully 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:Twenty-three subjects (41.0 ± 6 years, 12.7 ± 5 years post-partum) were included. Women with a history of preeclampsia (n=11) were compared to a control group of women with prior normotensive pregnancy (n=12) (Figure 1A). Obesity and diabetes were more common with preeclampsia, but there was no significant difference in the presence of hypertension between the groups (Table 1A). There was no difference in stress MBF. However, preeclampsia was associated with higher rest MBF (1.47 ± 0.54 mL/g/min vs. 1.19 ± 0.29 mL/g/min; p=0.07) and MPR (1.96 ± 0.46 vs 2.66 ± 1.0; p=0.02) compared to normotensive pregnancy (Figure 1). Similarly, corrected MPR remained significantly lower with prior preeclampsia versus uncomplicated pregnancy (2.36 ± 1.0 vs 3.36 ± 1.46; p=0.03).Conclusions:In this study, we observed significantly reduced coronary microvascular function following a pregnancy complicated by preeclampsia at least 5 years postpartum. Heightened cardiovascular risk factors may attenuate this association; however, these observations indicate that systemic microvascular dysfunction in preeclampsia also involves the coronary microcirculation. Further research is needed to better understand the timing and association of these microvascular changes concerning preeclampsia and later heart disease.

Circulation, Volume 150, Issue Suppl_1, Page A4133257-A4133257, November 12, 2024. Background:Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). Recent epidemiological studies have revealed an association between ketone bodies (KB) and adverse cardiovascular outcomes, offering a unique insight into metabolic health and its impact on mortality risk. Elevated levels of both Lp(a) and KB may synergistically amplify pathological processes, including endothelial dysfunction, inflammation, and oxidative stress, through their involvement in shared pathophysiological pathways, thereby exacerbating disease progression beyond the impact of each biomarker individually.Methods:Utilizing data from the UK Biobank, KB were measured by nuclear magnetic resonance spectroscopy and serum Lp(a) concentrations were measured using an immunoturbidimetric assay. Four groups were created as follows: Group 1: Lp(a)

Circulation, Volume 150, Issue Suppl_1, Page A4132820-A4132820, November 12, 2024. Connexin-43 (Cx43) plays a critical role in the propagation of action potentials among cardiomyocytes and proper cardiac contractility. In healthy cardiomyocytes, Cx43 is located at the intercalated disk; however, Cx43 remodeling is observed in cardiac pathologies and is linked with arrhythmogenesis and sudden cardiac death. Utilizing a mouse model of Duchenne muscular dystrophy (DMDmdx), we have previously demonstrated that cardiac Cx43 is laterally localized, forming undocked hemichannels that activate via S-nitrosylation in response to isoproterenol-evoked cardiac stress. This activation leads to the disruption of cardiac membrane permeability, triggered activity, and deadly arrhythmogenic behaviors. To establish the direct role of S-nitrosylated Cx43 in DMD cardiomyopathy, we developed a specific knock-in mouse line in which the single Cx43 site for S-nitrosylation, cysteine 271 (Cys271), was substituted with a serine (C271S+/-). Here, we developed a DMDmdx:C271S+/-line (4–6 months old), exhibiting reduced levels of S-nitrosylated Cx43 after crossing DMDmdx mice and C271S+/-mouse lines to assess the effect of β-adrenergic stimulation-induced cardiac stress and heart dysfunction. We show that cardiac Cx43 remodeling was not prevented in DMDmdx:C271S+/-, similar to what was shown in DMDmdxmice via immunofluorescence analysis. In addition, DMDmdxmice displayed an increased number of deadly arrhythmogenic events, increased Ca2+signaling, and prolonged action potentials in Langendorff-perfused whole hearts via optical mapping, compared to wild-type and DMDmdx:C271S+/-mice. Similarly, isoproterenol treatment evoked severe myocardial injury, increased levels of plasmatic cardiac troponin I (cTnI), and 40% mortality in DMDmdxmice. Notably, DMDmdx:C271S+/-mice, similar to DMDmdxmice treated with the Cx43 hemichannel blocker Gap19, exhibited cardioprotection compared to the cardiac dysfunction observed in DMDmdxmice. Therefore, these findings strongly suggest that S-nitrosylation of Cx43 proteins at site Cys271 represents a fundamental NO-mediated mechanism involved in the induction of arrhythmias and myocardial injury in DMDmdxafter β-adrenergic stress.

Circulation, Volume 150, Issue Suppl_1, Page A4146210-A4146210, November 12, 2024. Introduction:Abdominal aortic aneurysm (AAA) is a major cardiovascular disease characterized by the dysregulation of vascular smooth muscle cell (VSMC) homeostasis. TCF7L2, a transcription factor involved in Wnt signaling, plays a key role in cell proliferation and differentiation. Genome-wide association studies (GWAS) have identified the gene as being positively associated with aortic aneurysms, but its specific impact and the underlying mechanisms on AAA remain unclear.Methods and Results:Two models were employed to induce AAA in VSMC-specificTcf7l2knockout (floxedTcf7l2/Myh11-CreERT2) mice: elastase- and AngII/BAPN-induced AAA models. TCF7L2 deficiency in VSMCs significantly alleviated AAA formation, aorta dilation, elastin degradation, and VSMC apoptosis in both models. In primary human aortic smooth muscle cells, small interfering RNA-mediated Tcf7l2 knockdown attenuated glycolysis and lactate production, as revealed by RNA sequencing, targeted metabolomics, lactate assay, and Seahorse Glycolysis Stress Test. TCF7L2 deficiency in VSMCs also inhibited cell migration, TNFα/CHX- and FasL-induced apoptosis. Conversely, adenovirus-mediated overexpression of TCF7L2 promoted these processes. We further performed Cut&Run sequencing and ChIP sequencing analysis, the data revealed that TCF7L2 binds to the promoter regions of Ldha/b and Tp53 genes, indicating that TCF7L2 promotes VSMC glycolysis and apoptosis through direct interaction with these key genes. Additionally, TCF7L2 upregulated the mRNA and protein expression of MMP14 in VSMCs, suggesting a mechanism by which TCF7L2 regulates extracellular matrix organization.Conclusions:Our data indicate that TCF7L2 plays a key role in AAA development by modulating VSMC glycolysis, apoptosis, migration, and extracellular matrix organization, highlighting TCF7L2 as a potential target for treating VSMC-related diseases.

Circulation, Volume 150, Issue Suppl_1, Page A4146447-A4146447, November 12, 2024. Introduction:Our previous study showed that endothelial cells (ECs), differentiated from human induced pluripotent stem cells (hiPSCs) derived from patients with type 2 diabetes (dia-hiPSCs), displayed impaired phenotypes and function, including lower intracellular glycine content, increased senescence and inflammation, and impaired mitochondrial function. Furthermore, of the four molecules that regulate glycine homeostasis (glycine transporter 1 and 2 and the cytoplasmic and mitochondrial serine hydroxymethyltransferases [cSHMT and mSHMT, respectively]), only mSHMT was downregulated in dia-hiPSCs derived ECs (dia-hiPSC-ECs). Thus, we aim to determine whether deficiency of mSHMT protein expression will impair EC phenotype and function due to increased oxidative stress.Methods:hiPSCs reprogrammed from the cells of healthy human subjects (nor-hiPSCs) were differentiated into ECs (nor-hiPSC-ECs), and transduced with adenoviral vectors carrying shRNA targeting mSHMT (Ad-shRNA/mSHMT) or Scramble (Ad-Scramble) for 48 hours, and cultured in endothelial growth medium for 14 days. Intracellular glycine content and ROS were measured by liquid chromatography and MitoSOX, respectively, cell senescence was assessed by β-galactosidase staining, mitochondrial membrane potential was visualized using JC-1 dye, and expression of intercellular adhesion molecule-1(ICAM-1, an indicator of inflammation) protein was evaluated via Western blot.Results:Ad-shRNA/mSHMT starting 25 infectious unit/EC dramatically inhibited mSHMT protein expression, which was accompanied with significantly reduced glycine content in nor-hiPSC-ECs. Compared to Ad-scramble transduced nor-hiPSC-ECs, down-regulation of mSHMT, caused by Ad-shRNA-mSHMT, resulted in significant increase of senescence (increased abundance of β-gal and P53 expression) and inflammation (increased ICAM-1 protein expression), and significant decline in mitochondrial membrane potential (reduced red fluorescence intensity) in nor-hiPSC-ECs. Although low intracellular cellular glycine level can lead to oxidative stress as it is required for glutathione synthesis, increased oxidative stress, by MitoSOX labeling, was not found in nor-hiPSC-ECs with mSHMT knockdown.Conclusion:Deficiency of mSHMT impairs nor-hiPSC-EC phenotype and function, which is independent of oxidative stress.

Circulation, Volume 150, Issue Suppl_1, Page A4148019-A4148019, November 12, 2024. Background:Heparan sulfate (HS) proteoglycans act as mechanosensors on endothelial cells (ECs), regulating EC morphology and function. HS expression is affected by culture under static or dynamic conditions. HS response to inflammatory stimulus under both conditions is not well characterized. This study investigated HS expression on human aortic ECs (HAECs) under static and arterial flow conditions.Hypothesis:Inflammation modeled by TNFa significantly decreases HS epitope on HAECs under both static and arterial flow conditions.Aims:To establish the effect of TNFa on HS expression in HAECs.Methods:Passages 4 through 8 HAECs (ATCC) were cultured to confluence in endothelial growth medium (Vasculife) in Ibitreat µ-Slide 8 well high chambered coverslip slides or Ibitreat µ-Slide VI 0.4 flow channel slides. Cells were treated with TNFa at 100 ng/mL for 3 hours under static conditions or conditioned with 10 dyn/ cm2 of shear stress for 24 hours and then treated with TNFa at the same concentration added to the circulating media for 3 hours. HAECs were fixed in 2% paraformaldehyde/ 0.1% glutaraldehyde for 30 minutes followed by blocking with 2% goat serum for 30 minutes, both at room temperature. Primary antibody to the 10E4 HS epitope was incubated at 4°C overnight (1:100; 10E4 epitope, AMS Biotechnology, USA) followed by incubation in Alexa Fluor 488 goat anti-mouse secondary antibody (1:300, Molecular Probes, USA) for 1 hour at room temperature. HAECs nuclei were stained using 4′,6-diamidino-2-phenylindole and immersed in phosphate buffered saline for confocal imaging using a laser scanning microscope (Zeiss, LSM 880, 20X).Results:TNFa significantly (p < 0.05) increased HS expression in HAEC monolayers treated under static conditions compared to untreated control and heparinase III treated HAECs (Figure 1A). HAEC monolayers conditioned under arterial shear stress expressed significantly (p < 0.05, ANOVA with Tukey’s post-hoc) higher HS levels compared to baseline static controls; however, flow conditioned HAECs did not show any difference in HS expression under untreated compared to TNFa conditions (Figure 1B).Conclusion:These data indicate that fluid shear stress may program endothelial cells to significantly alter their HS expression and response to inflammatory stimuli.

Circulation, Volume 150, Issue Suppl_1, Page A4140997-A4140997, November 12, 2024. Aim:Right ventricle to pulmonary circulation (RV-Pc) uncoupling represents a mainstay in staging progression of heart failure (HF), being an independent predictor of mortality. In addition, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a well-established diagnostic and prognostic serum biomarker. In lack of clear clinical evidences on the relationship between exercise levels of NT-proBNP and RV-Pc uncoupling, this represents the aim of our investigation.Methods and Results:A cohort of 13 HF stable patients (mean age 71.6 ± 8.1; 48% female, mean left ventricular ejection fraction 57±13%) underwent maximal exercise stress echocardiographic and cardiopulmonary exercise testing (iCPET) with RV 3D-imaging analysis and were compared with a control population. Natriuretic peptides levels were obtained at rest and peak exercise. RV-Pc coupling was addressed by using the length-force relationship TAPSE/PASP ratio (tricuspid annular plane systolic/excursion pulmonary arterial systolic pressure). As expected, HF patients exhibited a higher level of NT-pro-BNP compared to controls (mean 831 ng/ml vs 131 ng/ml, at rest; mean 793.3 vs 138 ng/ml at peak). In HF, TAPSE/PAPS at peak exercise decreased compared to rest (0.73 ± 0.19 vs 0.47 ± 0.15 respectively) with an inverse correlation between NT-pro-BNP and TAPSE/PAPS exercise (r=0.60, p

Circulation, Volume 150, Issue Suppl_1, Page A4139373-A4139373, November 12, 2024. Introduction:Takotsubo cardiomyopathy (TCM) is a transient condition characterized by left ventricular dysfunction, often triggered by stress, although its exact pathogenesis remains unclear. We are presenting a case of TCM triggered by an acute manic episode, shedding light on the interplay between psychological states and cardiac function. Additionally, this case underscores the heightened risk of QT prolongation and ventricular fibrillation associated with antipsychotic medications.Case Description:A 32-year-old female with a history of bipolar I disorder was admitted to the psychiatric unit for an acute manic episode and was immediately started on Olanzapine. On the second day of admission, the patient collapsed and was found to be in ventricular fibrillation. After three cycles of cardiopulmonary resuscitation and two direct current shocks, the patient achieved a return of spontaneous circulation and sinus rhythm. She was intubated and transferred to the ICU, where an EKG revealed a QTc of 497 ms (Figure.2). A follow-up EKG after 12 hours showed dynamic T-wave inversions and a prolonged QTc of 615 ms (Figure.1). Echocardiography indicated apical akinesis with severely decreased systolic function, with an ejection fraction of 30%. CT coronary angiography was normal. The patient was diagnosed with Takotsubo cardiomyopathy and started on metoprolol. On the fourth day of admission, an automatic implantable cardioverter-defibrillator was implanted. At six-month follow-up, the patient’s EKG showed a normal QTc of 420 ms (Figure. 2), and echocardiography demonstrated an improved ejection fraction of 55%.Conclusion:This case supports the hypothesis of catecholamine-induced myocardial stunning as a primary mechanism of TCM, illustrated here in the context of acute mania. Physicians should consider TCM as a potential complication of acute mania. Screening EKGs in patients experiencing manic episodes could be beneficial. If abnormalities are detected, serial EKGs, echocardiography, and medication adjustments may help prevent this potentially fatal consequence of acute mania. Although Olanzapine is not strongly linked to QTc prolongation compared to some other atypical antipsychotics, diligent electrocardiographic monitoring and close observation for any QTc prolongation are crucial. These measures play a pivotal role in preventing potentially fatal consequences associated with cardiac arrhythmias.

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

Circulation, Volume 150, Issue Suppl_1, Page A4143615-A4143615, November 12, 2024. Background:A coronary artery calcium score of zero (CAC=0) is generally accepted as a marker of a very low 5y risk for coronary events. However, whether the prognostic value of CAC=0 varies by sex is unclear. For example, non-atherosclerotic causes of coronary ischemia present more often in women, including spontaneous coronary artery dissection and microvascular angina, which may be undetected by CAC. Further, CAC is performed at a later age in women. Whether these factors impact the utility of CAC=0 in women vs men is uncertain.Methods:We tested whether the prognostic value of CAC=0 differs by sex. We searched the Intermountain Health electronic medical record (eMR) database for patients (pts) at primary coronary risk who underwent positron emission tomography/computed tomography (PET/CT) stress testing and had a zero CAC score. We assessed coronary prognosis (i.e., coronary death [CD] or non-fatal myocardial infarction [MI]) during follow-up. Primary events were adjudicated by chart review. We compared outcomes in women vs. men. Given the small number of events, chi-square rather than time-to-event analyses were performed. We also compared all-cause death or MI rates in those with CAC=0 vs. CAC >0 by sex.Results:The eMR search identified19,495 women and 20,523 men undergoing PET/CT who were at primary coronary risk. Of these, 7967 (19.9%) had CAC=0 on CT. Of CAC=0 patients, 5400 (67.8%) were women and 2567 (32.2%) were men. Overall age averaged 60.5y (SD 12.0) in women and 53.8y (SD 12.6) in men. In total, 13 events occurred (MI=12, CD=1) over a follow-up of 2.1y (SD 1.6). By sex, 7 events (0.13%) occurred in CAC=0 women and 6 (0.24%) in men (p=0.28). Rates of all-cause death or non-fatal MI comparing CAC=0 to CAC >0 were 3.3% vs 9.5% in women and 3.3% vs 10.2% in men (both p