Risultati per: Incontinenza urinaria da stress o mista

Circulation, Volume 146, Issue Suppl_1, Page A11938-A11938, November 8, 2022. Background:BP risk class assessment has been relying on resting BP (rBP) measurements by healthcare providers. Often, this measurement does not correlate with 24-hour ambulatory BP monitoring nor with at-home measurements.Purpose:To assess whether abnormal rise in BP post-mild exercise protocol (PMEP), which resembles most of the activities subjects are under all day, will be more physiologic and informative for risk stratification, beyond the rBP measurements.Methods:We screened 2,924 subjects, ages 20-79, for CVD risk using the Early Cardiovascular Disease Risk Scoring System, also known as the Rasmussen Risk Score, which consists of 10 tests: 7 vascular and 3 cardiac (published previously). The vascular tests include rBP, BP PMEP (2.4 mi/hr and 7% elevation for 3 minutes), small (C2) artery stiffness, and CIMT. Out of the total subjects, 1094 (37%) were asymptomatic and on no medications. These were divided into four BP classes according to the current ACC/AHA guidelines.Results:In the table, normotension with an abnormal rise in BP PMEP has significant cardiovascular structural and functional abnormalities (CVSFA) than those without. Also noted, the higher the BP class, the higher the CVSFA with and without an abnormal rise in BP PMEP.Conclusions:Abnormal rise in BP PMEP in normotensive subjects is associated with significant CVSFA. This may represent a “masked hypertension” cohort. These findings mandate early diagnosis, follow-up, and optimal treatment. Additionally, an abnormal rise in BP PMEP in other classes is more pronounced with stepwise increases in BP class. Hence, we advocate for PMEP for BP classification and treatment. Early detect to protect.

Circulation, Volume 146, Issue Suppl_1, Page A11298-A11298, November 8, 2022. Mitochondria are double-membraned organelles indispensable in metabolically active organs such as the heart. Much of the mitochondrial proteome is encoded by the nuclear genome and requires import into mitochondria via channels present on the outer and inner mitochondrial membranes. If protein import goes awry at any step, it can cause unimported mitochondrial proteins to accumulate in the cytosol, leading to mitochondrial Precursor Overaccumulation Stress (mPOS). Defects in mitochondrial protein import have been linked to many forms of heart disease such as Senger’s syndrome, cardiac arrhythmia, and chronic atrial fibrillation. The A123D mutation in adenine nucleotide translocase 1 (Ant1), an ATP/ADP antiporter present on the mitochondrial inner membrane, has been shown to cause hypertrophic cardiomyopathy, while other mutations inAnt1(A114P, A90D, V289M, L98P) have been shown to cause Autosomal Dominant Progressive External Ophthalmoplegia. Our studies suggested that the mutant ANT1 can cause mitochondrial protein import clogging. To characterize the pathophysiology induced by mitochondrial protein import clogging, we developed a mouse model (the “clogger mouse”) expressing two clinically relevant mutations inAnt1, namelyA114PandA123D. While prior work on this model revealed a low-penetrant neurodegenerative and mild myopathic phenotype, the impact of this mutation on the heart has not been studied. In the current study, we show that expression of Ant1A114P, A123Dhas little effect on mitochondrial respiration and heart function. This is consistent with the rapid degradation of Ant1A114P, A123Din the heart. Interestingly, transcriptomic analysis revealed an altered expression of circadian regulator and output genes such asClock,Ciart, Per1-3, CebpbandHlfin the clogger mouse relative to wild type. These data suggest that mitochondrial protein import clogging can induce a stress response independent of bioenergetics. It also led us to hypothesize that the circadian pathway plays a role in adapting to mitochondria-induced proteostatic stress in the heart. Our current experiments focused on testing this hypothesis are anticipated to help us understand how the heart can uniquely adapt to mitochondrial protein import clogging.

Circulation, Volume 146, Issue Suppl_1, Page A13684-A13684, November 8, 2022. Background:Obesity and sex have a complex relationship with myocardial ischemia. We explored the association of sex and severe obesity with adverse cardiovascular outcomes in patients with ischemic exercise stress echocardiography (EXE).Methods:We retrospectively studied 142 patients with ischemic ExE [Age: 65±11 years, 70(49%) women, EF: 57±8%, body mass index (BMI): 28±6 kg/m2]. Severe obesity (BMI >35 kg/m2) occured in 48 (34%) patients. Patients were stratified based on obesity and sex (4 groups, women, and men with and without severe obesity), followed for median of 1.5 years, and compared for clinical, exercise variables and occurrence of composite outcomes (death, acute coronary syndrome, cardiac hospitalization and repeat ischemia testing).Results:In our study, 28(20%) women and 20(14%) men had severe obesity, and 42(29%) women and 52(37%) men had no severe obesity. Groups were not different for age, risk factors, exercise characteristics, and resting LV function. Outcomes occurred in 85(60%) patients and were more prevalent in women with severe obesity compared to women without or men with or without severe obesity [21(75%), 17(40%), 11(55%), and 35(67%), p=0.014]. Sex and severe obesity did not predict outcomes in isolation [HR: 1.13 (95%CI:0.74 to 1.73), 1.48 (95%CI:0.95 to 2.3), respectively, figure 1A, B]. Survival analysis showed that women without severe obesity were at lowest risk, men were at similarly elevated risk irrespective of severe obesity, and women with severe obesity were at highest risk for composite outcomes [p=0.037, figure 1C, HR: 2.5 (95% CI: 1.3 to 4.8)]. After adjusting for clinical, exercise, and echocardiographic variables, women with severe obesity remained at high-risk [HR: 2.2, (95% CI: 1.06 to 4.36)].Conclusion:In patients with ischemic ExE, women with severe obesity are at higher risk for adverse cardiac outcomes. Future studies are needed to understand the pathophysiologic mechanisms underlying this association.

Circulation, Volume 146, Issue Suppl_1, Page A14955-A14955, November 8, 2022. Psychosocial stressors (e.g., anxiety, personality traits, social isolation) are risk factors for cardiovascular events and heart disease. However, there is a lack of knowledge regarding the biological mechanisms that underlie this risk-outcome relationship. To address this knowledge gap, our team uses two non-traditional animal models, the Syrian hamster (Mesocricetus auratus) and gray short-tailed opossum (Monodelphis domestica). We previously reported that social isolation-induced aggression, a type of psychosocial stress experience, leads to increased neural activation in the ventral tegmental area (VTA) of the midbrain. The VTA contains tyrosine hydroxylase (TH)-producing (putative dopamine, DA) neurons and is innervated by vasopressin (AVP) fibers. DA and AVP play a role in social behavior, and we investigated whether these two systems interact when an individual experiences psychosocial stress-induced aggression. Here we report that social interactions increased Fos, the protein product of the immediate early genec-fosthat serves as a marker of neuronal activation, in non-TH cells in an area of the VTA called the interfascicular nucleus (IF) of male subjects. Previous social experience increased the number of TH-positive cells in the IF but had no effect on the number of AVP-ir fibers. Conversely, levels of aggressive and social dominance behaviors were positively correlated with the number of AVP-ir fibers in the IF, whereas there was no relationship between these behaviors and the number of TH-positive cells. In socially naïve males, AVP microinjected into the VTA inhibited the duration of aggressive behavior. We are currently investigating the impact of our psychosocial stress paradigms on myocardial injury in both males and females. Our results suggest a complex interaction between AVP and DA systems in the brain in psychosocial stress responses. Our long-term goal is to build on these preliminary findings to determine whether AVP in the VTA may reduce psychosocial stress-induced myocardial injury, a first step in exploring heart-brain interactions that may link psychosocial stress with negative cardiovascular disease outcomes.

Circulation, Volume 146, Issue Suppl_1, Page A13635-A13635, November 8, 2022. Introduction:Among females in the United States, Black females suffer from the highest rates of hypertension, coronary artery disease, and total cardiovascular disease (CVD) mortality. Vascular endothelial dysfunction precedes overt CVD and predicts CVD risk and has been reported in this population, but this is not always a consistent finding. Although psychosocial stress from numerous sources likely contributes to this disparity, the precise pathways and mechanisms remain incompletely understood. A growing literature suggests that internalization and coping may be more important than exposure to stressors alone. Therefore, we examined the relationship between endothelial function (brachial artery flow-mediated dilation, FMD) and psychosocial stress exposure (adverse childhood experiences, ACEs; past week discrimination, PWD) versus internalization/coping (John Henryism Active Coping Scale, JHAC12; Giscombe Superwoman Schema Questionnaire, G-SWS-Q). We hypothesized that 1) FMD would be blunted in Black relative to White females and 2) among Black females, internalization and maladaptive coping would exhibit a stronger negative relationship with FMD than exposure to stressful experiences alone.Methods:Twelve Black (21 ± 3 yr) and 8 White (25 ± 6 yr) healthy females underwent standard FMD testing. Black participants completed the ACEs, PWD, JHAC12, and G-SWS-Q inventories. Higher scores indicated greater stressor exposure or endorsement of the internalization/coping constructs.Results:Brachial artery FMD was lower in Black relative to White females (4.93 ± 3.10 vs 8.58 ± 1.62%;p< .01). Neither ACEs (r= -.10,p= .75) nor PWD (r= -.24,p= .45) were associated with FMD. JHAC12 scores were (r= -.61,p= .02) and SWS scores tended to be (r= -.39,p= .11) negatively associated with FMD. Among the SWS subscales, SWS-Resistance to Being Vulnerable (r= -.51,p= .04) and SWS-Intense Motivation to Succeed (r= -.54,p= .04) were negatively associated with FMD.Conclusion:These preliminary data indicate that 1) brachial artery endothelial function is blunted in young Black females and 2) reduced vascular function in Black females may be due more to internalization and maladaptive coping than exposure to stressful experiences alone.

Circulation, Volume 146, Issue Suppl_1, Page A11029-A11029, November 8, 2022. Mitochondrial diseases are some of the most common genetically inherited disorders, yet the prognosis for affected patients has not drastically improved in recent years. Most therapies are supportive as the underlying biochemical derangements in these diseases are incompletely understood. Mitochondrial functions rely on the import of nuclear-encoded proteins, and it has recently been appreciated that defective import of mitochondrial proteins can result in the cytosolic accumulation of these preproteins. The accumulation of these preproteins results in cellular toxicity independently of any changes to the mitochondrial bioenergetic function, raising the possibility that mitochondrial protein import stress may be a yet uncharacterized pathway that links mitochondrial dysfunction with pathology. Here, we model this cytosolic mitochondrial precursor overaccumulation stress (mPOS) in mice through overexpression of the inner mitochondrial membrane protein Adenine Nucleotide Translocase 1 (ANT1). The goal of this study is to determine whether ANT1 can induce mPOS and tissue remodeling prior to the onset of cardiac bioenergetic defects. Using isolated cardiac mitochondria from these mice, we detected a moderate decrease in the levels of Complex I, II ,and IV. By measuring oxygen consumption in these mitochondria from 2-month-old animals, we found only a mild reduction in complex II based state 3 and 4 respirations. No change in complex I-based state 3 and 4 respirations was observed. Using RNAseq and western blot analysis, we find the robust activation of the integrated stress response (ISR). Transcriptomic data further demonstrates a strong upregulation of transcripts involved with 1-carbon metabolism, the amino acid starvation response, and proteolysis. Using echocardiographic evaluation of heart function on anesthetized mice at 6 months old, we find no significant alteration in systolic function. Together these data support the idea that mPOS may be a potent trigger of the ISR in a bioenergetics-independent manner. Whether activation of the ISR can alter cardiac function later in life is being evaluated.

Circulation, Volume 146, Issue Suppl_1, Page A9764-A9764, November 8, 2022. Introduction:Hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI) is able to yield important information regarding molecular and functional imaging in a one-stop examination. The aim of this study was to investigate the relationship between coronary flow reserve (CFR) and left ventricular longitudinal strain (LVLS) using simultaneous acquisitions on hybrid13N-ammonia PET/MRI.Methods:Thirty-eight patients with suspected coronary artery disease (CAD) who underwent13N-ammonia PET/MRI were enrolled. Vasodilator stress was induced by intravenous injection of adenosine. CFR was calculated from dynamic acquisition of13N-ammonia PET. LVLS was evaluated by feature-tracked MRI. Myocardial flow reserve (MFR) and LVLS values were based on a 17-segment model and three coronary territories, left anterior descending artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA).Results:We analyzed 577 myocardial segments in the left ventricle. LVLS under vasodilator stress was significantly increased compared with LVLS at rest in myocardial segments with MFR ≥2.0 (P

Circulation, Volume 146, Issue Suppl_1, Page A11202-A11202, November 8, 2022. Introduction:Caregivers of patients with heart failure (HF) are at high risk of low quality of life due to stress-related to caregiving. Self-reported measures are commonly used to assess relatively long-term stress related to caregiving. Still, biological markers of stress, a short-term stress measure, are rarely used. There is limited knowledge on whether both can predict the quality of life in caregivers of patients with HF.Hypothesis:The stress biomarker (serum cortisol) and subjective distress related to caregiving (Caregiver Burden Inventory) predict the quality of life in caregivers of patients with HF.Methods:In this cross-sectional study, Taiwanese caregivers of patients with HF completed surveys including stress-related caregiving and quality of life measured by the Caregiving Burden Inventory and the Short Form-36, respectively. A blood sample for serum cortisol was collected between 9 and 12 AM. Independent t-test and multivariable linear regression analysis were conducted adjusting for age, gender, education, marital status, relationship with care-recipient and depressive symptoms (Patient Health Questionnaire).Results:Of the 113 caregivers (mean age 54.5 years, 70.8% female, 78% married/cohabitated), 59% cared for patients with NYHA class III/V. Single caregivers had higher serum cortisol levels than married caregivers (11.4 vs. 8.5, p =.002). Males had a significantly higher serum cortisol level than females (10.7 vs. 8.5, p =.010), but males reported a lower caregiver burden than females (1.3 vs. 1.6, p =.049). Both serum cortisol (β =-.36, P=.012) and caregiver burden (β = -.29, P= .018) were significant predictors of physical well-being. Serum cortisol (β= -.28, p=.026) and caregiver burden (β =-.25, p =.027) also significantly predicted mental well-being.Conclusions:Although stress levels are different by caregivers’ characteristics, both cortisol level and self-report caregiver burden have similar predictability of quality of life in caregivers of patients with HF. Reducing stress and caregiver burden is necessary to improve the quality of life in this population.

Circulation, Volume 146, Issue Suppl_1, Page A10706-A10706, November 8, 2022. Soluble guanylyl cyclase (GC1) is an α/β heterodimer producing cGMP when stimulated by nitric oxide (NO). The NO-GC1-cGMP pathway is essential for cardiovascular homeostasis. Oxidative stress is known to disrupt the NO-GC1-cGMP pathway via oxidation of GC1 cysteines, which makes it unresponsive to NO stimulation. Under these conditions, GC1-α subunit “moonlights” by increasing cellular S-nitrosation via specific transfer of its nitrosothiols to cysteines of other proteins (transnitrosation). One of the SNO-targets identified by Mass Spectrometry (MS) was the oxidized form of Thioredoxin1 (oTrx1), which is unidirectionally transnitrosated by GC1 with αC610 as a SNO-donor and C73 of Trx1 as the SNO-recipient. Because oTrx1 itself drives transnitrosation, we sought and MS-identified SNO-proteins targeted by both GC1 and Trx1, suggesting a SNO-GC1→oTrx1→targets cascade. We investigated the (patho)physiological relevance of GC1-dependent transnitrosation activity by creating a knock-in (KI) mice with replacement of αC610 to a serine (αC610S). Biotin switch assays confirm that, under oxidative stress (Angiotensin II (AngII) treatment), global and Trx1 levels of S-nitrosation (SNO) were drastically reduced in lungs and hearts of KI mice compared to WT but the NO-stimulated GC1 activity was similar between WT and KI. Importantly, telemetry recordings indicated that 2 weeks of AngII treatment led to a more severe increase in BP and a more prolonged QTc in KI mice. The AngII-induced rise in MBP was 27.6 ± 2.5 mmHg in KI vs 21.6 ± 1.2mmHg in WT, while AngII-increase in QTc, reflecting delayed repolarization, was 12.53 ± 2.30ms in KI vs. 8.713 ± 2.72ms for the WT. The elevated BP with AngII treatment correlated with higher increase in cardiac hypertrophy, oxidation (measured by DHE staining) and fibrosis (picric acid staining) in KI mice. The AngII-induced increase in a) hypertrophy in KI was 0.63 ± 0.07 vs. 0.24 ± 0.08 mg/g in WT, b) cardiac oxidation was 0.19 ± 0.07 in KI and negligible in WT, and c) fibrosis was 1.75 (A.U) in KI vs. 1.31 in WT. These more severe cardiovascular dysfunctions in KI mice in response to AngII suggest that transnitrosation by GC1, potentially using oTrx1 as a nitrosothiol relay, is a mechanism of protection against oxidative stress.

Circulation, Volume 146, Issue Suppl_1, Page A14940-A14940, November 8, 2022. Introduction:Failure of multidrug therapy and the multifactorial nature of kidney injury has paved the path way regenerative medicine with over 45 clinical trials using stem cells-based therapy underway. Neonatal cardiac mesenchymal stem cells (nMSC) are one of the most potent stem cells due to their secretome. HYPOTHESIS: SOD2 and anti-inflammatory miRNAs (miR-214 & 95p) in paracrine secretions (secretome) of nMSC provides renoprotection in a rodent model of glycerol-induced AKI.Methods:nMSC were generated from neonatal myocardium using enzymatic digestion and antibodies-based selection. Secretome was collected by conditioning nMSCs for 72 hours in serum free basal medium. Human kidney cells (HKC) were used forin vitroanti-oxidation assays using cisplatin. THP-1 cells were used for anti-inflammatory assessment. CD1 mice were used for glycerol-induced AKI model. Mice were subjected to AKI via IM glycerol (9mg/kg). nMSC-derived secretome was intravenously administered immediately after, or 4 hours post-glycerol. Blood urea nitrogen (BUN) and creatinine were analyzed in serum. Cell survival/KIM1 was assessed by immunohistology/FACS. Other experiments utilized cisplatin toxicity in HKC.Results:Administration of nMSC secretome (5 or 10mg/kg) at the same time or 4-hours post-glycerol administration significantly reduced serum creatinine and BUN in a glycerol induced AKI animal model. Caspase-9 and KIM1 expression was significantly decreased in tubular cells as compared to placebo at a dose of 10mg/kg. KIM-1 was significantly downregulated as compared to placebo following nMSC-secretome administration. Western blot analysis of HKC treated with cisplatin in presence of nMSC-secretome showed significant reduction in NFkb and pERK expression (p

Circulation, Volume 146, Issue Suppl_1, Page A110-A110, November 8, 2022. Background:Vagus nerve stimulation (VNS) has been shown to improve survival and neurological outcomes after cardiac arrest (CA) and resuscitation by improving mitochondrial function, increasing cerebral blood flow, and reducing inflammation. However, the therapeutic cellular and subcellular mechanisms of VNS are not clearly understood in CA injury. Endoplasmic reticulum (ER) stress after cardiac arrest also contributes to cell death and is an underexplored area.Objective:The aim of this study was to investigate the protective effects of customized threshold-adjusted VNS (tVNS) in a rat model of CA and resuscitation in reducing ER stress and cell apoptosis.Methods and Results:Sprague-Dawley rats underwent 12 min asphyxial-CA followed by resuscitation. Rats were assigned to either post-resuscitation tVNS for 2 h or no-tVNS (control). tVNS was applied by electrode placement in the left cervical vagus nerve immediately after resuscitation. The tVNS was determined by a 15-20% reduction from the immediate baseline heart rate as the effective and physiological threshold for each animal. This enabled customized parameters for individual animals. At 2 h post-ROSC, rats were perfused with normal saline, and the whole brain was removed. The whole brain was then processed for protein expression by western blotting. We also prepared sham rats that did not receive CA or tVNS. For measuring ER stress we evaluated the expression of p-IRE1α protein and for apoptosis, we measured p-BAD protein. We observed a significantly higher protein expression of p-IRE1α in whole brain tissue after CA in control groups in comparison to the sham (p

Circulation, Volume 146, Issue Suppl_1, Page A10484-A10484, November 8, 2022. Introduction:Carotid plaque is recommended for cardiac risk stratification for intermediate risk patients but has not been integrated into cardiology community clinics to help refine testing and reduce risk for major adverse cardiovascular events (MACE). The purpose was to determine the clinical usefulness of carotid plaque score (PS) to guide management of low-intermediate risk patients.Methods:Patients 40-75 years who received a carotid ultrasound were followed up to 10 years for MACE (cardiovascular death, myocardial infarction, stroke). Low-intermediate risk participants (n = 9,114) with no known cardiovascular disease were included. Administrative data holdings housed at IC/ES were used for event follow-up. Kaplan-Meier curves and Cox proportional hazard ratios determined relative risk. Combining plaque score (Rotterdam method, plaque presence within carotid segments, PS 0 to 6) with stress echo (SE) was assessed in a subset of participants (n = 624).Results:The optimum threshold for PS = 2 for 1-year MACE (AUC = 0.738). The population rate of MACE over 10 years was 4%. In participants referred for SE, PS of

Circulation, Volume 146, Issue Suppl_1, Page A14139-A14139, November 8, 2022. Introduction:AHA guidelines recommend non-invasive cardiac testing (NIT) within 72 hours after an emergency department (ED) evaluation for suspected acute coronary syndrome (ACS), after acute myocardial infarction (AMI) has been excluded. However, the effectiveness of this strategy to reduce the risk of future AMI or death, in low-risk patients is contested.Hypothesis:We hypothesized that in patients with low risk based on history, electrocardiogram, age, risk factors and troponin (HEART) based scoring, early NIT may not be beneficial compared to higher risk.Methods:We compared the effectiveness of early NIT vs. no early testing, in a retrospective cohort of adult (age ≥18) members of the Kaiser Permanente Southern California health system from 05/2016-12/2020. We included all adults presenting at EDs with suspected ACS and who had data to compute HEART score. We stratified the cohort into low risk (score 0-3); intermediate risk (score 4-6) and high-risk (score ≥7) based on HEART score. Within each group, confounder adjusted instrumental variables models were used to evaluate the marginal effect of early NIT, and the number needed to treat (NNT) was calculated as the inverse of the absolute composite risk reduction in death/AMI within 30 days of ED discharge.Results:The cohort included 174,936 patients [61% Low risk (mean age 53; female 58%; early NIT 5%), 36% intermediate risk (mean age 71; female 72%; early NIT 18%), and 3% high risk (mean age 74, female 45%; early NIT 23%)]. The risk reduction in 30-day death/AMI due to early NIT increased progressively through the intermediate-risk (NNT = 59) and high-risk groups (NNT = 24) (Table 1). Risk reduction in the low-risk group was not statistically significant.Conclusions:HEART score based high risk patients may benefit the most from early NIT. However, the majority of the suspected ACS cohort was classified as low risk and the benefit of early NIT on 30-day death/AMI was uncertain in this low-risk group.

Circulation, Volume 146, Issue Suppl_1, Page A13918-A13918, November 8, 2022. Introduction:Stress cardiomyopathy (SC) and anterior ST elevation myocardial infarction (AMI) share similar clinical and echocardiographic features on initial presentation, complicating their differentiation. Previously, subtle differences in 12-lead ECG between the two have been reported.Hypothesis:We propose that higher precordial R-wave amplitude on ECG and lower biomarkers values can serve as reliable predictors of SC during initial triage.Methods:Among patients admitted to a single center from 2015-2019 undergoing left heart catheterization (LHC) for suspected AMI, 76 patients with either LHC-proven SC or AMI (38 each) were included. All patients had transthoracic echocardiography (TTE) performed within 24 hours of LHC. Patients were excluded when TTE quality was poor. Left ventricular ejection fraction (LVEF) and speckle-tracking global longitudinal strain (GLS) were calculated from transthoracic apical views. Non-parametric variables were analyzed using Wilcoxon rank sum test. Sensitivity and specificity analyses were performed using ROC curves.Results:LVEF (33+9% vs 33+8%) and GLS (-7.5+2.8% vs -7.9+3.3%) were similar in both groups. R-wave amplitude in ECG leads V1-V2 was higher in SC compared to AMI (V1: 0.96 vs 0.54 mV, p = 0.035; V2: 1.46 vs 0.75 mV, p = 0.037). At index admission, peak pro-BNP was higher (22198 vs 3098, p = 0.002) and peak Troponin-T (1.43 vs 236, p

Circulation, Volume 146, Issue Suppl_1, Page A14078-A14078, November 8, 2022. Objectives:In pulmonary hypertension associated with HFpEF (PH-HFpEF), identifying mechanisms of right ventricular: pulmonary arterial (RV:PA) uncoupling can be leveraged for sub-phenotyping and targeted therapies. In this study, we aim to distinguish mechanisms of RV:PA uncoupling in PH-HFpEF due to high RV afterload (afterload-sensitive; AS) and impaired left ventricular-interventricular septal contributions to RV function (ventricular interdependence; VI).Methods:Subjects (n=13) with early-stage PH (per echo) and NYHA II-III dyspnea were prospectively enrolled. Exclusion criteria: advanced disease with NYHA IV, LVEF

Circulation, Volume 146, Issue Suppl_1, Page A14065-A14065, November 8, 2022. Introduction:While a link between chronic stress and cardiovascular disease (CVD) is well established, the neurocircuit alterations underlying this association remain unclear. We leveraged advanced multimodal imaging to gain insights into neurocircuit alterations that associate with atherosclerosis.Methods:Individuals with posttraumatic stress disorder (PTSD), trauma-exposed controls without PTSD (TC), and healthy controls (HC) were prospectively enrolled. Participants underwent whole-body18F-fluorodeoxyglucose positron emission tomography/magnetic resonance (FDG-PET/MR) imaging. Stress-related neural network activity (SNNA) was assessed on PET as amygdala metabolic activity relative to regulatory (ventromedial prefrontal cortex [vmPFC]) activity. The structural integrity of the uncinate fasciculus, the major white matter tract connecting the amygdala to vmPFC, was assessed using diffusion tensor imaging (DTI). Atherosclerotic burden was assessed on MR as vessel normalized wall index and standard deviation (SD) of vessel wall thickness.Results:Of 91 participants (24 PTSD, 42 TC, 24 HC), 57% were female, and the median age was 37 years. Compared to controls, individuals with PTSD had higher SNNA (Fig 1A) and lower uncinate fasciculus integrity (Fig 1B). SNNA and uncinate fasciculus integrity were negatively correlated (r = – 0.30, p=0.008). Those with PTSD had higher ascending aorta normalized wall indices (p=0.018, adjusted for Framingham risk score). Notably, the SD of carotid wall thickness correlated positively with SNNA and negatively with uncinate fasciculus integrity (Fig 1C & D).Conclusion:These findings suggest that increases in the amygdala relative to vmPFC metabolic activity or disruptions of their structural interconnections may potentiate atherosclerosis. Interventions targeting this stress-related neural network may reduce adverse brain-heart interactions and related cardiovascular disease burden.