Circulation, Volume 146, Issue Suppl_1, Page A14263-A14263, November 8, 2022. Introduction:The presence of pulmonary vascular disease (PVD) may be under-recognized during standard hemodynamic evaluation in patients with Fontan physiology. Assessment of pulmonary vascular reserve (VR) (Δ pulmonary artery pressure/Δ cardiac index) utilizing pharmacologic stress testing could be a better way of identifying PVD in pediatric patients. The objective of this study is to diagnose Fontan patients with PVD utilizing pharmacologic stress testing.Hypothesis:Pharmacologic stress testing will unmask Fontan patients as having PVD.Methods:Single center record review of cardiac catheterizations with dobutamine administration in Fontan patients from January 2021 to June 2022. Following acquisition of baseline data on room air, a dobutamine infusion was started at 5 mcg/kg/min with dose escalation as needed until an appropriate heart rate response was achieved. Hemodynamics were reassessed at each dose interval, but data are reported at the highest cardiac index (CI). Abnormal VR was defined as > 3 mmHg/l.Results:Eighteen Fontan patients (87% male) were included. Median age at the time of catheterization was 14 (IQR 11, 16) years with mean duration of Fontan circulation of 9.9 ± 3.9 years. The primary indication for catheterization was exercise intolerance (65%). Dobutamine administration did not result in a significant change in indexed pulmonary vascular resistance (PVRi) (2.1 ± 0.8 v 2.4 ± 1.31 iWU, p = 0.21) or Fontan pressure (12 [IQR 11, 14] v 14 (IQR 12, 15), p=1.0]. Eight patients had a PVRi ≥ 2.0 iWu at baseline; while 4 (22% of the cohort) had a PVRi < 2.0 iWU at baseline but had an abnormal VR.Conclusions:PVD is common in Fontan patients but may be missed in some patients without pharmacologic stress testing. Accurate diagnosis of PVD will allow for optimization of Fontan circulation with pulmonary vasodilators.
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Abstract 11237: Dose Response and Long QT Genotype During Exercise Stress Testing in Children
Circulation, Volume 146, Issue Suppl_1, Page A11237-A11237, November 8, 2022. Introduction:Beta-blockers (BB) are first-line therapy for long QT syndrome (LQTS). Many physicians rely on repeated exercise stress tests (ESTs) to establish the optimal dose in each patient.Hypothesis:Increased BB dose is associated with a decrease in maximum heart rate, influenced by precision-medicine factors including genotype.Methods:Retrospective chart review of treadmill ESTs with the outcome variable “% predicted heart rate (HR)” = (maximum HR achieved/(220-age))*100. Genotype positive patients had pathogenic or likely pathogenic variants, re-adjudicated in 2022. Doses of BB other than nadolol were converted to nadolol equivalents using an established methodology.Results:We evaluated 345 ESTs in 132 LQTS patients (58% genotype positive) from 2003-21. The mean age at first EST was 12.5 years (standard deviation 4.0 years). Most patients were prescribed nadolol (59%) or atenolol (28%). When controlled for person-level fixed effects, we observed an inverse relationship between BB dose and % predicted HR. The dose-response slope was steeper in genotype positive patients than genotype negative patients (-4.8 vs. -3.3,Figure, p
Abstract 14174: Abnormal Exercise Electrocardiography With Normal Stress Echocardiography is Associated With Increased Subclinical Coronary Atherosclerosis: Insights From the Project Baseline Health Study
Circulation, Volume 146, Issue Suppl_1, Page A14174-A14174, November 8, 2022. IntroductionPatients with an abnormal (positive) exercise electrocardiography (ECG), but normal stress echocardiography (+ECG/-Echo) have more adverse cardiac events than patients with a negative ECG and normal stress Echo (-ECG/-Echo). However, it is unclear if ECG/Echo discordance is associated with a greater burden of concurrent subclinical coronary atherosclerosis.MethodsIn the Project Baseline Health Study (PBHS), participants underwent stress Echo and a coronary artery calcium (CAC) scan. For this PBHS substudy, participants with no known coronary artery disease (CAD) were analyzed by stress result: -ECG/-Echo, +ECG/-Echo, or +Echo (with or without +ECG). Patients with a submaximal stress test, uninterpretable ECG, resting wall motion abnormality, and/or baseline ejection fraction
Abstract 13610: Imbalance Between GCN5L1 Mediated CypD Acetylation and Sirt3 Deacetylase Promotes Mitochondrial Oxidative Stress, Endothelial Dysfunction and Hypertension
Circulation, Volume 146, Issue Suppl_1, Page A13610-A13610, November 8, 2022. Nearly half of adult population has hypertension which is a main risk factor for cardiovascular disease. Mitochondrial dysfunction contributes to hypertension and targeting mitochondria can potentially improve treatment of hypertension. We found hyperacetylation of mitochondrial Cyclophilin D (CypD) in essential hypertension and proposed that CypD acetylation can promote endothelial dysfunction and hypertension. CypD acetylation is mediated by general control of amino acid synthesis 5 like 1 (GCN5L1) protein which is counteracted by deacetylase Sirt3. We tested potential role GCN5L1 and Sirt3 in endothelial dysfunction and hypertension. Western blot of aortic mitochondria showed an increased GCN5L1 level in hypertensive mice coupled with the reduction of Sirt3 deacetylase resulting in 250% increase in GCN5L1/Sirt3 ratio promoting CypD acetylation. We reported pathogenic role of lipid oxidation products isolevuglandins (isoLGs) and scavenging isoLGs by mitochondria-targeted mito2HOBA reduces mitochondrial acetylation. We tested if mitochondrial isoLGs contributes to acetylase/deacetylase imbalance driving CypD acetylation. Treatment with mito2HOBA improves Sirt3 expression and reduces GCN5L1 level resulting in normalization of GCN5L1/Sirt3 ratio and reduced CypD acetylation. To define the pathophysiological role of GCN5L1 in endothelial cells we tested if GCN5L1 depletion prevents cytokine-induced of mitochondrial oxidative stress. Indeed, treatment of human aortic endothelial cells with AngII+TNFα induces mitochondrial O2.-, however, GCN5L1 depletion using siRNA completely abrogated the cytokine-induced mitochondrial oxidative stress. To define the role GNC5L1 in pathogenesis of endothelial dysfunction we developed new tamoxifen-inducible endothelial specific GNC5L1 knockout mice (EcGNC5L1KO). Depletion of endothelial GCN5L1 reduces vascular mitochondrial O2.-, prevents inactivation of endothelial nitric oxide and preserves endothelial dependent relaxation in angiotensin II-infused EcGNC5L1KOmice compared with wild-type littermates. These data support the pathogenic role of GNC5L1 in CypD acetylation and endothelial dysfunction and targeting GNC5L1 can be beneficial in cardiovascular disease.
Abstract 15536: Surface Lin28a Expression Consistent With Cellular Stress Parallels Indicators Of Senescence
Circulation, Volume 146, Issue Suppl_1, Page A15536-A15536, November 8, 2022. Aims:Declining cellular functional capacity resulting from stress or aging is a primary contributor to impairment of myocardial performance. Molecular pathway regulation of biological processes in cardiac interstitial cells (CICs) is pivotal in stress and aging responses. Altered localization of the RNA binding protein Lin28A has been reported in response to environmental stress, but the role of Lin28A in response to stress in CICs has not been explored. Surface Lin28A redistribution is indicative of oxidative stress response in CIC associated with aging and senescence.Methods and Results:Localization of Lin28A was assessed by multiple experimental analyses and treatment conditions and correlated to oxidative stress, senescence, and ploidy in adult murine CICs. Surface Lin28A expression is present on 5% of fresh CICs and maintained through passage 2, increasing to 21% in hyperoxic conditions but lowered to 14% in physiologic normoxia. Surface Lin28A is coincident with elevated senescence marker p16 and beta-galactosidase (β-gal) expression in CICs expanded in hyperoxia, and also increases with polyploidization and binucleation of CICs regardless of oxygen culture. Transcriptional profiling of CICs using single cell RNASeq reveals upregulation of pathways associated with oxidative stress in CICs exhibiting surface Lin28A. Induction of surface Lin28A by oxidative stress is blunted by treatment of cells with the antioxidant Trolox in a dose-dependent manner, with 300uM Trolox exposure maintaining characteristics of freshly isolated CICs possessing low expression of surface Lin28A and β-gal with predominantly diploid content.Conclusion and Clinical Perspective:Surface Lin28A is identified as novel surface marker of oxidative stress conditions that cause DNA damage and cellular senescence. Accumulation of surface Lin28A was inhibited by antioxidant treatment with lowered indices of cellular stress and senescence, revealing the potential of surface Lin28A as a diagnostic stress marker. Therapeutic strategies targeted toward surface Lin28 expression set the stage for next generation senolytics to remove stressed or senescent cells and promote recovery from tissue injury or aging.
Abstract 15616: Single Cell Transcriptomic Profiling Identifies Ferroptosis and Oxidative Stress as Potential Drivers of Muscle Dysfunction in Pad
Circulation, Volume 146, Issue Suppl_1, Page A15616-A15616, November 8, 2022. Introduction:Peripheral artery disease (PAD) affects >8 million people nationwide and is disabling. PAD-associated myopathy causes weakness yet is understudied. Unbiased transcriptomic profiling of muscle satellite cells (MuSC) which drive recovery may elucidate the etiology of ischemic myopathic change.Hypothesis:MuSC in PAD differentially express injury associated pathways that may be novel targets for intervention to reduce ischemic myopathy.Methods:Muscle tissue biopsies were obtained during lower extremity amputation or bypass in PAD/ischemic (N=4; ABI
Abstract 14230: Comparing Stress Echocardiography Parameters of Transgender Women With Their Cisgender Counterparts: The Mayo Clinic Women’s Heart Clinic
Circulation, Volume 146, Issue Suppl_1, Page A14230-A14230, November 8, 2022. Introduction:Stress echocardiography (SE) is a common functional imaging modality used for the detection of symptomatic coronary artery disease (CAD). Currently, the interpretation of SE relies on sex-based comparators for reporting parameters, including exercise time and functional aerobic capacity. These parameters are based on the cisgender male and female populations but have not been studied among transgender (TG) patients. Thus, we sought to characterize the SE parameters among a group of TG women.Methods:We designed a case-control study of TG women who underwent a SE at the Mayo Clinic. Each TG patient was age-matched with 2 cis-males and 2 cis-females. Demographics, medical history, and SE data were extracted. Conditional logistic regression analysis was performed to compare the TG cohort with each cisgender cohort separately.Results:Among the 43 TG females (age 57.7±9 years, 94.9% white), the prevalence of CAD was less than in cis-males (p=0.013) but similar to cis-females. For SE parameters, TG females had higher resting heart rates than cis-males (median [Q1, Q3]: 80 [71,93] vs 70 [64, 77]; p=0.002). Double product (24816 [21156, 27864] vs 26864 [22444, 30660]; p=0.016), exercise time (7.3 minutes [6,9] vs 8.5 [7.2, 9.5]; p=0.041), and metabolic equivalents (8.2 [7, 10] vs 9.5 [8.2, 10.5]; p=0.018), were all lower in TG females than cis-males. Exercise ejection fraction was higher in the transgender cohort than in cis-females (70 [70, 75] vs 70 [65, 70]; p=0.007). There was no difference in functional aerobic capacity or in the rest or stress wall motion score indices among the groups. Finally, there was no difference in the prevalence of positive electrocardiogram or SE studies.Conclusion:In conclusion, we report for the first time SE profiles for TG females which display an overall distinct phenotype compared to cis-males and cis-females. Larger prospective studies are warranted to further define these parameters for the TG population.
Abstract 14359: Impact of Marital Stress on 12-month Health Outcomes Among Young Adults With Acute Myocardial Infarction
Circulation, Volume 146, Issue Suppl_1, Page A14359-A14359, November 8, 2022. Background:Psychosocial stress is associated with worse cardiac outcomes, but little is known about the prognostic impact of marital stress in young adults (≤55 years) with acute myocardial infarction (AMI). We investigated the association between marital stress and 1-year health outcomes in young AMI survivors.Methods:We used data from the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), which enrolled people aged 18-55 years with AMI (2008-2012). Marital stress was assessed among married/partnered participants at 1 month post-AMI using the Stockholm Marital Stress Scale, categorized as absent/mild, moderate, and severe. Main outcomes were physical/mental health status, generic/disease-specific quality of life, angina, depressive symptoms, and all-cause readmission at 1 year post-AMI. Linear and logistic regression models were sequentially adjusted for baseline health status, demographics, and socioeconomic factors (including education level, income level, employment status, and insurance status).Results:Among the 1593 married/partnered participants in our study, more women reported severe marital stress than men (39.4% vs 30.4%, p=0.001). Having severe marital stress was associated with worse physical and mental health, lower generic and cardiovascular-specific quality of life, more angina and depressive symptoms, and 1.48 times higher all-cause readmission at 1 year post-AMI. These associations remained significant after adjusting for baseline health score and patient demographics (Table Model 1), but they attenuated and became non-significant when further adjusting for socioeconomic factors (Model 2).Conclusion:Marital stress was associated with worse health outcomes in young AMI patients, which can be partially mediated by socioeconomic factors. Further research is needed to understand this complex relationship and potential causal pathway associated with these findings.
Abstract 10720: Early Growth Trajectory is Associated With Post-Traumatic Stress in Parents of Infants With Congenital Heart Disease
Circulation, Volume 146, Issue Suppl_1, Page A10720-A10720, November 8, 2022. Background:Parents of infants with congenital heart disease (CHD) have described substantial stress over infant growth. Poor growth trajectory (GT) during early infancy may be a source of traumatic stress. The purpose of this study was to determine if differences exist in parent posttraumatic stress (PTS) between parents of infants with healthy versus poor GTs from hospital discharge to 4 months post discharge.Methods:This secondary analysis of a previously reported RCT (REACH telehealth trial NCT01941667) included parents of infants with CHD with stress measures at discharge and study end (n=136). Posttraumatic Diagnostic Scale was used to measure PTS. Weights were converted to weight for age Z scores (WAZ) using World Health Organization standards. WAZ-GT classes were identified using latent class growth modeling. We used multivariate logistic regression modeling to examine associations between WAZ-GT and parental PTS over the study period, adjusting for covariates.RESULTSOne-quarter of parents (n=37, 28%) demonstrated at least moderate PTS symptom severity at discharge and one-third at study end (n=40, 31%). We identified four distinct classes of infant WAZ-GT (Figure). Among the identified GTs, two were considered healthy growth patterns: “stable around WAZ=0” (n=51, 37.5%) and “maintaining WAZ > 0” (n=12, 8.8%). Therefore, these two patterns were collapsed to serve as one reference group for the analysis. Two additional WAZ-GT classes were identified that reflected poor growth: “partially-recovered” (n=44, 32.4%) and “never-recovered” (n=29, 21.3%). Parents of infants in the “never recovered” GT were at greater risk (OR=4.58; CI=1.54-13.64) for experiencing at least moderate PTS symptom severity at end of study as well as over time from discharge to end of study (OR=3.91; CI=1.60-9.86).CONCLUSIONResults offer new insights that parents of infants with poor GT are at increased risk for persistent PTS and may need additional screening and intervention.
Abstract 11065: Stress T1 Mapping Demonstrates Coronary Microcirculatory Dysfunction in Both Nonhypertrophied and Hypertrophied Myocardium of Hypertrophic Cardiomyopathy
Circulation, Volume 146, Issue Suppl_1, Page A11065-A11065, November 8, 2022. Introduction:Coronary microcirculatory dysfunction (CMD) in hypertrophic cardiomyopathy (HCM) is associated with clinical deterioration. We have shown that stress T1 mapping could detect CMD of hypertrophied interventricular septum (IVS). However, CMD in nonhypertrophied left ventricular free wall (LVFW) has not been fully elucidated.Hypothesis:We assessed the hypothesis that regional CMD in LVFW of HCM can be detected using stress T1 mapping.Methods:We evaluated 36 consecutive subjects (26 HCM patients and 10 control subjects, mean age: 61±3 years) who underwent CMR at 3T. Cine imaging, rest and adenosine stress T1 mapping, late gadolinium enhancement (LGE) and phase-contrast imaging of coronary sinus flow were performed. The T1 values at rest and after adenosine stress were measured as an averaged T values of 3 short-axis slices of LV myocardium and T1 reactivity (ΔT1) was calculated as follows: ΔT1 (%) = (T1stress – T1rest)/T1rest х 100. Coronary flow reserve (CFR) was measured coronary sinus blood flow during adenosine stress divided by that at rest.Results:The T1 values at rest were significantly higher in HCM than control (1245±9ms vs. 1196±11ms, p=0.0027), and the T1 values after adenosine stress significantly increased in both groups (HCM: 1285±10ms, p=0.0018 vs. rest, control: 1244±9ms, p=0.0128 vs. rest, Figure 1). Both IVS and LVFW demonstrated significantly lower ΔT1 in HCM than control (IVS: 3.95±0.35% vs. 5.68±0.41%, p=0.0163, LVFW: 4.80±0.39% vs. 6.75±0.65%, p=0.0163, Figure 2). CFR in HCM significantly decreased than that in control (2.48±0.40 % vs. 5.97±1.31 %, p=0.0051). Multiple regression analysis revealed that ΔT1 of both IVS and LVFW was correlated with CFR (β=0.527, p=0.0026, β=0.445, p=0.0325).Conclusions:T1 reactivity significantly decreased in both nonhypertrophied and hypertrophied myocardium of HCM compared to control. Stress T1 mapping have the advantage of being able to estimate regional CMD in addition to global CMD.
Pathways between neighbourhood factors, stress and glycaemic control in individuals with type 2 diabetes in Southeastern United States: a cross-sectional pathway analysis
Objectives
Understanding the pathway by which neighbourhood factors influence glycaemic control may be crucial to addressing health disparities in diabetes. This study aimed to examine if the pathway between neighbourhood factors and glycaemic control is mediated by stress.
Design
Structured equation modelling (SEM) was used to investigate direct and indirect effects in the relationship between neighbourhood factors, stress and glycaemic control, with standardised estimates to allow comparison of paths.
Participants
Data was obtained from 615 adults with type 2 diabetes in the Southeastern United States.
Primary and secondary outcome measures
The primary outcome variable was glycaemic control determined by glycated haemoglobin (HbA1c) within the prior 6 months. Neighbourhood factors included neighbourhood violence, aesthetic quality of the neighbourhood, access to healthy food, and social cohesion. Stress was measured using the perceived stress scale.
Results
In the final model (2(158)=406.97, p
Revisione sul trattamento dell’incontinenza urinaria nelle donne
Correction: Post-traumatic stress disorder psychological interventions in sub-Saharan Africa: protocol for a systematic review of the literature
Ntlantsana V, Molebatsi K, Mashaphu S, et al. Post-traumatic stress disorder psychological interventions in sub-Saharan Africa: protocol for a systematic review of the literature. BMJ Open 2022;12:e052903. doi: 10.1136/bmjopen-2021-052903.
The authors want to alert the readers on the updated Funding statement.
Funding: The publication was financially supported by the Schizophrenia Research Society (SIRS), and by the University of KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP).
Perceived stress and associated factors among pregnant women during COVID-19 pandemic period in Northwest Ethiopia, 2020: a cross-sectional study
Objective
This study aimed to determine the prevalence and associated factors of perceived stress among pregnant women during the COVID-19 pandemic period in Northwest Ethiopia.
Method
A cross-sectional study.
Setting
University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia.
Participants
A total of 415 pregnant women were recruited by using a systematic random sampling technique from 28 April 2020 to 12 June 2020.
Measurement
The required data were collected through face-to-face interviews. The Perceived Stress Scale was used to assess perceived stress. The Edinburgh Postnatal Depression Scale and Oslo Social Support Scale 3 were used for associated factors. The data were analysed by using SPSS V.20. We also included sociodemographic, obstetrical and gynaecology, substance use and intimate partner-related factors. Logistic regression analysis was used to identify associated factors with perceived stress. Bivariate and multivariable logistic regression analyses were used to identify the effect of each independent variable with the outcome variable. A p value of less than 0.05 was considered to be statistically significant.
Results
A total of 415 pregnant women participated in the study with response rate of 98.57%. The prevalence of perceived stress is found to be 13.7% (95% CI=10.4% to 17.1%). According to the multivariable logistic regression result, being a student (adjusted OR (AOR)=9.67, 95% CI=2.739 to 34.183), being at the first and third trimesters of gestational age (AOR=3.56, 95% CI=1.065 to 11.885; AOR=4.80, 95% CI=1.851 to 14.479, respectively), and having antenatal depression (AOR=3.51, 95% CI=1.628 to 7.563) were factors positively associated with perceived stress.
Conclusion
The prevalence of perceived stress among pregnant people was relatively high. This study recommends that all pregnant people should be screened and treated for perceived stress particularly during the first and third trimesters. Emphasis should be given to early detection and treatment of antenatal depression. Pregnant students must be strongly evaluated and intervened for perceived stress.
Mitochondrial Stress Induces an HRI-eIF2α Pathway Protective for Cardiomyopathy
Circulation, Volume 146, Issue 13, Page 1028-1031, September 27, 2022.
Early interventions for post-traumatic stress following musculoskeletal trauma: protocol for a systematic review and meta-analysis
Introduction
Post-traumatic stress symptoms (PTSS) can be triggered following exposure to a traumatic event, such as violence, disasters, serious accidents and injury. Little is known about which interventions provide the greatest benefit for PTSS. This systematic review aims to estimate the effects of early interventions on PTSS following musculoskeletal trauma.
Methods/analysis
Development of this review protocol was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols checklist. This review will include randomised controlled trials and non-randomised controlled studies evaluating the effect of early (within 3 months of a traumatic event) non-pharmacological and non-surgical interventions on PTSS in adults (aged ≥18 years). MEDLINE, PsycINFO, Embase, CINAHL, Zetoc, PROSPERO, Web of Science, PubMed and Google Scholar, as well as key journals/grey literature, will be searched from inception to 31 July 2022. Only articles published in English will be considered. Two independent reviewers will search, screen studies, extract data and assess risk of bias using the Cochrane Risk of Bias tool V.2 (RoB 2) and the Risk Of Bias in Non-randomised Studies of Interventions (ROBINS-I), respectively. Mean difference or standardised mean difference (SMD) will be extracted with accompanying 95% CIs and p values where these are reported. Group effect size will be extracted and reported. Symptoms of PTSS will be ascertained using SMDs (continuous) and diagnosis of PTSS using risk ratio (dichotomous). If possible, study results will be pooled into a meta-analysis. A narrative synthesis of the results will be presented if heterogeneity is high. The overall quality of evidence and risk of bias will be assessed using the Grading of Recommendations Assessment, Development and Evaluation, RoB 2 and ROBINS-I guidelines, respectively.
Ethics and dissemination
Ethical approval is not required for this systematic review since data from published studies will be used. This review is expected to provide a better understanding of the effect of early intervention for PTSS following musculoskeletal trauma. Findings of this review will be disseminated in peer-reviewed publications and through national and international conferences.
PROSPERO registration number
CRD42022333905