Risultati per: Incontinenza urinaria da stress o mista

Objectives
This goal of this research is to present a comprehensive method for evaluating stress and the factors that contribute to it in mothers of premature babies.

Design
Analytical cross-sectional study.

Setting
Data were collected from inpatient service for preterm infants including neonatal intensive care unit, and neonatal step-down units of the Aga Khan University Hospital—a private tertiary care hospital in Karachi, Pakistan.

Participants
Mothers aged 18 years and above who delivered preterm infants (gestational age of preterm below 37 weeks) in a private tertiary care hospital in Karachi, Pakistan.

Primary outcome
Stress in mothers of preterm infants.

Results
200 participants with a mean age of 30.12 years (SD ±5.21) were assessed. The level of stress identified using the perceived stress scale (PSS) among mothers who had delivered preterm infants was significantly higher as compared with other countries around the world. Based on the criteria of PSS scoring, the majority of the participants (92%, n=184) were categorised as having high perceived stress and 8% (n=16) of the mothers fell into the category of moderate stress.

Conclusions
The study findings suggest high levels of perceived stress among mothers of preterm infants. The factors associated with the stress among mothers of preterm infants included immunisation of newborn, education and occupation status of mothers, substance abuse by mother, gender preference from family, planning for further children, consumption of balance diet, education status of husband, mode of socialisation, years of marriage and hours of sleep.

Objectives
We conducted an implementation science mental health treatment study in western Kenya, testing strategies for scale up of evidence-based mental health services for common adult disorders using a non-specialist workforce, integrated with existing primary care (Sequential Multiple, Assignment Randomized Trial of non-specialist-delivered psychotherapy (Interpersonal Psychotherapy) and/or medication (fluoxetine) for major depression and post-traumatic stress disorder (PTSD) (SMART DAPPER)). Because study launch coincided with the COVID-19 pandemic, participants were allowed to attend treatment visits via mHealth (audio-only mobile phone) or in-person. We conducted a secondary data analysis of the parent study to evaluate preference for mHealth or in-person treatment among our study participants, including rationale for choosing in-person or mHealth treatment modality, and comparison of baseline demographic and clinical characteristics.

Design, setting, participants and interventions
Participants were public sector primary care patients at Kisumu County Hospital in western Kenya with major depression and/or PTSD and were individually randomised to non-specialist delivery of evidence-based psychotherapy or medication (n=2162).

Outcomes
Treatment modality preference and rationale were ascertained before randomised assignment to treatment arm (psychotherapy or medication). The parent SMART DAPPER study baseline assessment included core demographic (age, gender, relationship status, income, clinic transport time and cost) and clinical data (eg, depression and PTSD symptoms, trauma exposures, medical comorbidities and history of mental healthcare). Given that this evaluation of mHealth treatment preference sought to identify the demographic and clinical characteristics of participants who chose in-person or mHealth treatment modality, we included most SMART DAPPER core measurement domains (not all subcategories).

Results
649 (30.3%) SMART DAPPER participants preferred treatment via mHealth, rather than in person. The most cited rationales for choosing mHealth were affordability (18.5%) (eg, no transportation cost) and convenience (12.9%). On multivariate analysis, compared with those who preferred in-person treatment, participants who chose mHealth were younger and had higher constraints on receiving in-person treatment, including transport time 1.004 (1.00, 1.007) and finances 0.757 (0.612, 0.936). Higher PTSD symptoms 0.527 (0.395, 0.702) and higher disability 0.741 (0.559, 0.982) were associated with preference for in-person treatment.

Conclusions
To our knowledge, this is the first study of public sector mental healthcare delivered by non-specialists via mHealth for major depression and/or PTSD in Sub-Saharan Africa. Our finding that mHealth treatment is preferred by approximately one-third of participants, particularly younger individuals with barriers to in-person care, may inform future mHealth research to (1) address knowledge gaps in mental health service implementation and (2) improve mental healthcare access to evidence-based treatment.

Trial registration number
NCT03466346.

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

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

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

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

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

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

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

Circulation, Volume 150, Issue Suppl_1, Page A4141350-A4141350, November 12, 2024. Background:Atrial fibrosis is crucial in developing atrial fibrillation (AF). Elevated atrial pressure may significantly mediate atrial fibrosis, yet its underlying mechanisms remain unclear.Methods:Patients with AF who underwent radiofrequency ablation were recruited. Clinical data, including high-density mapping and imaging information, was analyzed. Multivariate regression analysis was performed to identify risk factors for low-voltage areas in the atrium. The CS-CREM mouse model, an autonomic AF model, was previously developed by our research group. Millar pressure catheters were used to measure left ventricular, right ventricular, and right atrial pressures in CS-CREM mice. Single-nucleus sequencing was employed to map the single-cell transcriptomes of atrial samples in CS-CREM and wild-type mice at different disease stages. Human primary atrial endocardial endothelial cells (ACCE) and HUVEC cell lines were subjected to mechanical stretch using the Flexcell tension system, followed by in vitro validation experiments. Mg101, a calpain inhibitor, was administered to CS-CREM mice for in vivo validation experiments.Results:Elevated atrial pressure in AF patients was identified as a significant risk factor for atrial fibrosis. Atrial pressure-related indices were linearly correlated with atrial fibrosis. Compared to wild-type mice, CS-CREM heterozygous mice exhibited significantly higher atrial pressure and aggravated atrial fibrosis. Single-nucleus sequencing revealed that atrial endocardial endothelial cells in CS-CREM mice underwent endothelial-mesenchymal transition (EnMT) into fibroblasts, with mechanical stress protein Flna being a critical regulatory protein. In vitro experiments demonstrated mechanical stretch-induced EnMT in ACCE and HUVEC cell lines. Mechanical stretch-activated mechanosensitive receptors on ACCE cell membranes led to increased intracellular calcium levels and calpain activation, which cleaved Flna into Flna 90. Flna 90 facilitated the nuclear translocation of transcription factor Smad3/7 and TGF-β, promoting the expressions of EnMT genes. This EnMT process was reversible with Mg101. In vivo experiments showed that Mg101 reduced the incidence of AF and mitigated atrial fibrosis in CS-CREM mice.Conclusion:Mechanical stress induces cleaved Flna 90 from Flna in atrial endocardial endothelial cells, thus assisting transcription factors Smad3/7 and TGF-β in nuclear translocation, regulating EnMT and mediating atrial fibrosis.

Circulation, Volume 150, Issue Suppl_1, Page A4142869-A4142869, November 12, 2024. Introduction:Adverse childhood experiences, also known as early life stress (ELS), are associated with increased risk of cardiovascular disease in later life, yet the underlying mechanisms remain elusive. Recent evidence indicates that parental life experiences can be transmitted to the offspring.Aim:To investigate the effects of ELS on cardiac structure and function in exposed parents and in their offspring, across 3 generations.Methods:We used ELS mouse model based on unpredictable separation of mouse pups (F1) from their mother (F0) each day for 3 hours from postnatal day 1 (PND1) to PND14 combined with dams exposure to an additional unpredictable stressor (forced swim in 18°C water for 5 minutes or 20-minute physical restraint in a tube) during separation. Control litters were raised normally. Echocardiography was performed at 6, 12 and 18 months in exposed animals (F0), their unexposed offspring (F1) and grand-offspring (F2). Both male and female mice were studied. Heart weight/tibia length was used to assess cardiac mass while Masson’s Trichrome was employed to detect fibrosis. Lung congestion was assessed as lung wet/dry weight ratio. Single-cell RNA sequencing (scRNAseq) was performed in MSUS and control hearts. A 6-week environmental enrichment (EE) program (cages containing running wheels, maze) was employed to test the possible rescue of ELS effects in adult males and their offspring.Results:F1 MSUS mice displayed increased LV mass, impaired diastolic function (assessed by conventional and tissue Doppler analysis) myocardial fibrosis and lung congestion. Time-dependent worsening of cardiac performance was observed from 6 to 18 months, both in males and females. ScRNAseq unveiled dysregulation of transcriptional programs underlying inflammation and lipotoxicity in the cardiomyocyte and endothelial cell clusters. MSUS offsprings did not show changes of cardiac function at 6 months, however diastolic dysfunction and lung congestion were observed at 12 and 18 months. A similar impairment of cardiac function was observed in the MSUS grandoffspring (F3). Of interest, 6-week exposure to an environmental enrichment protocol was able to improve LV mass, diastolic function and lung congestion in 12 months-old MSUS mice.Conclusions:ELS induces a transgenerational transmission of cardiac phenotypic alterations which can be rescued by EE. Our results shed light on the potential role of ELS on heart failure development and potential mitigation strategies.

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

Circulation, Volume 150, Issue Suppl_1, Page A4145408-A4145408, November 12, 2024. Background:Stress cardiomyopathy (SCM) is rarely triggered by ketamine and seldom leads to cardiogenic shock. Ketamine-induced catecholaminergic surge can lead to myocardial stunning with transient ischemia and subsequent reversible heart failure. Mechanical circulatory support can be successfully leveraged in SCM-associated cardiogenic shock while awaiting myocardial recovery.Case Presentation:A 28-year-old female with chronic pain was admitted for failure to thrive secondary to opioid-induced gastroparesis. The patient was weaned off opiates while on ketamine over 4 days. After halting ketamine, the patient had a cardiac arrest with eventual return of spontaneous circulation. After being extubated, she developed chest pain, hypotension, and ventricular tachycardia with anterolateral ST elevations, troponin leak, and lactic acidosis. TTE revealed an EF

Circulation, Volume 150, Issue Suppl_1, Page A4141357-A4141357, November 12, 2024. Background:Cardiac allograft vasculopathy (CAV) is a rapidly progressive form of coronary atherosclerosis limiting long-term survival after heart transplantation.Objectives:We evaluated the diagnostic and prognostic yield of quantitative stress cardiovascular magnetic resonance (CMR) perfusion for CAV detection in heart transplant recipients.Methods:Patients who received orthotopic heart transplants and underwent stress CMR for CAV assessment were included in the study and followed up for almost 2 years (median 1.8; IQR 0.9,2.7). The diagnostic accuracy of qualitative and quantitative stress CMR was assessed by calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), using invasive or CT coronary angiography as the reference for CAV detection. The area under the curve (AUC) was compared for qualitative and quantitative stress CMR. Adjusted hazard ratios for major adverse cardiac events (MACE), including death and unplanned cardiac hospitalizations were derived in all patients. The global myocardial perfusion reserve index (MPRi) was obtained by normalization to the rate-pressure product.Results:In a cohort of 60 patients, n=18 (30%) had significant CAV (grade 2 or 3), and n=11 (18.3%) experienced MACE. At the Youden index threshold of 2.1, the myocardial perfusion reserve index (MPRi) demonstrated a sensitivity of 85.7%, a specificity of 70.3%, a PPV of 52.2%, and an NPV of 92.9%. The MPRi was significantly more accurate than visual assessment (p < 0.001) in identifying underlying CAV (Figure 1) and it was an independent predictor of MACE (HR:0.26;95%CI:0.07,0.93; log-rank p=0.022; Figure 2), while the visual presence of inducible myocardial perfusion defect did not (HR:2.23;95%CI:0.57,8.66; p=0.2).Conclusions:In patients with previous heart transplantation, quantitative stress CMR perfusion has incremental diagnostic and prognostic value over qualitative stress CMR for the non-invasive detection of CAV.

Circulation, Volume 150, Issue Suppl_1, Page A4138946-A4138946, November 12, 2024. Background:Psychological stress affects cardiovascular (CV) health via multiple physiological and behavioral pathways. Few studies have assessed whether psychological stress impacts heart failure (HF) incidence. A prior large cohort study identified unique associations between perceived stress and HF subtype, but these associations were confounded by other health risk factors (e.g., prevalent baseline CV disease). No prospective study has evaluated these associations in women free of baseline CV disease.Goal:To evaluate the prospective association of psychological stress with incident HF and HF subtype risk in post-menopausal women.Hypothesis:Psychological stress is prospectively associated with an increased HF hospitalization risk, which may vary by HF type (HFpEF vs. HFrEF).Method:Of 29,703 post-menopausal women enrolled in the Women’s Health Initiative (WHI) free of baseline CV disease and pre-existing HF at first adjudication, psychological stress was assessed via an 11-item scale of stressful life events (SLE) over the past year (WHI screening, 1993-1998) and the 4-item Perceived Stress Scale (PSS; WHI Extension 2, 2010-2015). Incident HF was confirmed via adjudication of self-reported first hospitalization. Cox proportional hazards models adjusting for demographic, medical, and lifestyle factors were used to calculate hazard ratios associating stress quartiles with incident HF, HFpEF, and HFrEF hospitalization.Results:At screening, women were 62±7 years, 49% from underrepresented racial and ethnic populations, and 59% were at least high school graduates. At baseline women reported a mean of 2±.01 SLEs over the past year. Mean PSS scores were 4.16±3.09. Over a median of 15 years, there were 1,624 incident HF events (HFpEF, n=998; HFrEF, n=626). In fully adjusted models neither the number of SLEs or PSS scores were associated with HF risk(Table 1).Conclusions:In this WHI cohort, the number of SLEs and perceived stress were not prospectively associated with risk of HF, HFpEF, or HFrEF hospitalization. Future research is needed to understand whether specific types of stressors, stress measured more proximally to HF onset, or lab-based stress assessments may capture an association of stress with HF risk.

Circulation, Volume 150, Issue Suppl_1, Page A4145174-A4145174, November 12, 2024. Background:Protein half-life and turnover are crucial for cellular function, especially under basal and stress conditions, often contributing to proteinopathies. While the impact of oxidative stress (OxS) on proteostasis is well-documented, the role of reductive stress, an overabundance of antioxidant status, in proteotoxic cardiac disease remains elusive.Hypothesis:Tested whether chronic reductive stress (cRS) impairs protein turnover and induce proteotoxic cardiac disease.Methods:In transgenic mice expressing constitutively active Nrf2 (caNrf2-TG) and non-transgenic controls (n=6/gp.), we examined the half-life and turnover rates of the myocardial proteome using D2O labeling and mass spectrometry.Results:We observed significant changes in the half-life of over 1,700 proteins, with approximately 1,200 proteins exhibiting increased half-life at 3 months, despite no noticeable defects in cardiac structure and function. Under OxS induced by isoproterenol (ISO), about 700 proteins showed reduced half-life, underscoring distinct regulatory mechanisms in protein turnover between cRS and OxS. Proteins with altered half-lives were involved in key cellular functions, including metabolism, signal transduction, immune response, transport, and cell cycle regulation under cRS, revealing novel targets undetected in an OxS context. Notably, distinct positive adaptive compensatory (59; p