Circulation, Volume 146, Issue Suppl_1, Page A10098-A10098, November 8, 2022. Introduction:Dobutamine and exercise stress echo are routinely performed on patients with advanced cirrhosis though have low sensitivity in this patient population, even when target heart rate is achieved. This is in part due to their unique cardiovascular physiology which is frequently marked by reduced peripheral vascular resistance with low blood pressure, impaired chronotropic response to stress, hyperdynamic left ventricular systolic function and elevated cardiac output. In the general population, achieving a rate pressure product (RPP), defined as peak systolic blood pressure multiplied by peak heart rate, > 25,000 is typically considered a high level of stress and is an adequate workload to detect ischemia, however this has not been validated in patients with advanced cirrhosis. We aimed to assess the impact of achieving a RPP > 25,000 on the ability of stress echo to detect obstructive coronary artery disease (CAD) in patients with advanced cirrhosis.Methods:We performed a case-control study on patients with advanced cirrhosis where 88 had and 97 did not have CAD based on invasive coronary angiography. A total of 159 patients (85.9%, 77 with CAD and 82 without) had dobutamine and 26 (14.1%, 11 with CAD and 15 without) had exercise as their stress modality. Continuous variables were compared by means of Wilcoxon Rank Sum test. Categorical variables were expressed as numbers and percentages and compared by means of chi-square and Fisher exact tests.Results:The average maximum RPP was 19,999 ± 4,969.4 with 32 patients (17.3%) achieving a RPP > 25,000 (14 with and 18 without CAD, P = 0.63). The average percent of maximum predicted HR (MPHR) achieved was 86.7 ± 9.2% with 136 patients (73.5%) achieving > 85% of MPHR. Achieving a maximum RPP > 25,000 (OR 0.83, 95% CI 0.39 – 1.79, P = 0.63) or a MPHR > 85% (OR 1.04, 95% CI 0.54 – 1.99, P = 0.92) did not improve the ability of stress echo to detect obstructive CAD.Conclusions:Achieving a maximum RPP > 25,000 did not improve the ability of stress echo to detect obstructive CAD in patients with advanced cirrhosis.
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Abstract 13379: Perceived Stress and Cardiovascular Risk Among Older Persons With HIV
Circulation, Volume 146, Issue Suppl_1, Page A13379-A13379, November 8, 2022. Background:Cardiovascular disease (CVD) is highly prevalent among older persons with HIV (OPWH) occurring on average a decade earlier than non-infected individuals largely due to chronic inflammation, vascular pathology, and psychosocial stressors. Effective cardiovascular risk reduction strategies such as exercise have been shown to lower both physiological and psychosocial stressors but have not been widely reported in the HIV population.Objective:To evaluate the effect of a one-year, moderate intensity aerobic exercise intervention on perceived stress among OPWH with ≥ 2 CVD risk factors.Methods:A secondary analysis was performed utilizing data from Project FiTBRAiN, a 2-arm RCT that included Let’s Move (moderate intensity aerobic exercise intervention) or Let’s Flex (flexibility/stretching attention control) groups. The 14-item Perceived Stress Scale (PSS) was utilized to measure participants’ perceived stress. Data analysis included an analysis of variance with pairwise and between-group differences reported.Results:Participants (n=115) reported a mean age of 55±5.2, and the majority were African American (n=100, 87.0%) and male (n=66, 57.4%). The most common cardiovascular comorbidities were elevated: total cholesterol (n=114, 99.1%), systolic blood pressure (n=108, 93.9%), diastolic blood pressure (n=98, 85.2%), and participants had a mean BMI of 28.29. Baseline 14-item PSS scores for the Let’s Move Program and Let’s Flex Program were 19.49 (SD=7.94) and 21.13 (SD=8.64), respectively, indicating moderate stress levels. Over all time points, the control group (Let’s Flex) had higher perceived stress than the intervention group (Let’s Move), but were not significant.Conclusions:Our findings suggest that moderate levels of psychological stress were present in this population and may be a risk factor for CVD among OPWH. The consistent finding that perceived stress remained lower over time indicates that aerobic exercise may be beneficial for stress reduction. Additional research is needed to determine the optimal dose and mode of exercise that is most beneficial for stress reduction in this population.
Abstract 10270: High Shear Stress Decreases ERG Causing Endothelial to Mesenchymal Transition and Pulmonary Arterial Hypertension
Circulation, Volume 146, Issue Suppl_1, Page A10270-A10270, November 8, 2022. Introduction:Computational modeling studies indicated that pathological high shear stress (HSS) of 100 dynes/cm2is generated in pulmonary arteries (PA) (100-500μM) in patients with a ventricular septal defect or idiopathic pulmonary arterial hypertension (PAH) and occlusive vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is a feature of PAH.Hypothesis:Pathological HSS induces EndMT, which contributes to the initiation and progression of PAH.Methods:We applythe Ibidi perfusion system to human PA endothelial cells (EC), to determine whether HSS (100 dynes/cm2) induces EndMT, when compared to normal laminar shear stress (LSS) (15 dynes/cm2). We assessed the mechanism and targeted it to prevent PAH in a mouse with HSS resulting from an aortocaval (AV) shunt.Results:HSS induced EndMT, as assessed by an increase in transcription factors, SNAI1 and SNAI2, reduced BMPR2 (previously shown to inhibit EndMT), decreased EC markers PECAM1 and CDH5, and increased mesenchymal markers, ACTA2 and FSP-1. While the flow-induced transcription factors, KLF2 and KLF4 were similar in LSS and HSS, the co-transcription factor ERG was reduced with HSS. IndeedERGsiRNA under LSS caused EndMT whereas under HSS, transfection ofERGprevented EndMT. To address the significance of our observations in an animal model we created an AV shunt in mice and compared PAH in those sham operated vs transfected with an adeno-associated viral (AAV2- ESGHGYF) vector selectively targeting PAEC with aluciferase(control) or anERGexpressing construct (N=10 per group). Eight weeks after AV shunt, right ventricular systolic pressures was 21.9 ±0.6 mmHg in sham, 37.2±1.0 mmHg in AV shunt with luciferase vector (p
Abstract 14807: Effect of Psychiatric Illnesses on the Stress Induced Cardiomyopathy Readmission
Circulation, Volume 146, Issue Suppl_1, Page A14807-A14807, November 8, 2022. Introduction:Stress-induced cardiomyopathy (SIC) is a form of transient non-ischemic cardiomyopathy that is precipitated in the setting of acute emotional or physical stress. Postulated hypothesis implicated catecholaminergic excess and a role of the brain-heart axis behind its pathogenesis. The impact of different psychiatric illnesses on the outcomes of SIC is not clear.Method:We conducted a retrospective study using National Readmission Database (NRD) from 2011 to 2019 using ICD-10-CM (International Classification of Diseases, 10th Edition, Clinical Modification) and ICD-9-CM codes to identify the admissions with the discharge diagnosis of SIC and stratified them based on the presence of psychiatric illnesses. The primary outcome was six-month readmission and predictors of readmission.Result:We included a total of 98,721 admissions with a diagnosis of SIC. Among them, 12.9% had major depression, 1.8% had bipolar disorder, 17.6% had an anxiety disorder, and 0.6% had schizophrenia. Overall, patients with psychiatric illnesses were younger. Patients with psychiatric illnesses had a higher burden of comorbidities. Patients with schizophrenia had higher in-hospital mortality. Patients with psychiatric illnesses had a higher likelihood of getting readmitted within six months (p
Abstract 11736: Role Alteration Predicts Post-Traumatic Stress, Anxiety and Depressive Symptoms in Parents of Infants With Congenital Heart Disease
Circulation, Volume 146, Issue Suppl_1, Page A11736-A11736, November 8, 2022. Background:Parents of infants born with congenital heart disease (CHD) are at increased risk for mental health problems, including anxiety, depression, and post-traumatic stress (PTS). Few studies have examined to what extent the hospital experience influences these mental health symptoms over time. The purpose of this pilot study was to determine hospital factors predicting parent anxiety, depression, and PTS at 3 months post-discharge.Methods:A convenience sample of 28 biological mother-father dyads was enrolled consecutively from August 2018 to October 2019 from one children’s hospital in the Northeast, US. Parents were instructed to complete questionnaires, including valid and reliable instruments for mental health symptoms, within one week of their infant’s surgery and 3 months post discharge. Associations between hospital factors and each mental health symptom at 3 months post discharge were assessed using linear mixed effects models, accounting for the anticipated correlation between parents of the same infant using an unstructured covariance matrix. Separate linear mixed effects models were constructed for each mental health symptom using backward selection method.Results:For each one unit increase in parental role alteration, anxiety symptoms were estimated to be increased by 5.98 (SE+1.60; p=0.002). Parents with at least a college education were estimated to have greater anxiety symptoms compared to parents with high school/technical school or less (10.89+3.75; p=0.009). For each one unit increase in role alteration, depressive symptoms were estimated to be increased (4.41+1.72; p=0.02). PTS was also significantly predicted by role alteration (5.06+1.91; p=0.02) along with timing of CHD diagnosis, with postnatal diagnosis estimated to increase PTS symptoms by 21.80 (SE+10.07; p=0.04) units compared to prenatal diagnosis.Conclusion:Role alteration experienced by parents during their infant’s hospitalization significantly predicts anxiety, depression, and PTS symptoms 3-months after discharge. Additional factors were identified that can inform mental health screening in this population. Future interventions to enhance the role of parents during infant hospitalization may support parent mental health post discharge.
Abstract 13208: Pathways Linking Posttraumatic Stress Disorder to Ischemic Heart Disease in Women Veterans
Circulation, Volume 146, Issue Suppl_1, Page A13208-A13208, November 8, 2022. Introduction:Posttraumatic stress disorder (PTSD) is associated with increased risk of ischemic heart disease (IHD). It is unclear if this excess risk is entirely mediated through traditional IHD risk factors (hyperlipidemia, hypertension, diabetes, and smoking). We examined 13 potential mediators of the PTSD-IHD association in a large cohort of women veterans: traditional risk factors, other conditions (obesity, chronic kidney disease, neuroendocrine disorders), women-specific risk factors (e.g., gestational diabetes and hypertension, pre-eclampsia), and psychiatric disorders (depression, anxiety, psychotic disorders, alcohol dependence, and drug dependence).Methods:The study cohort included women veterans ≥18 years of age who were enrolled in Veterans Health Administration care between 1/1/2000 to12/31/2017. Diagnosis of each risk factor and disorder was based on administrative billing codes (International Classification of Disease versions 9 and 10). The final study cohorts included 1:2 propensity-score matched group of patients with and without PTSD respectively. The cohorts were matched for age, number of prior visits, and presence of the above risk factors. Cox regression examined associations of PTSD with time to development of the above 13 risk factors. Cox regression with time-varying covariates was used to model time to development of IHD as a function of PTSD and each of above 13 risk factors as time-varying predictors in separate models.Results:The cohorts included 132,293 patients with, and 265,846 patients without PTSD. PTSD was positively associated with each of the 13 risk factors. Results are tabulated in the table below.Conclusion: Traditional risk factors cumulatively accounted for just one third of the risk of IHD posed by PTSD, and all examined risk factors accounted for less than half of the increased risk associated with PTSD. More research is needed to identify pathways by which PTSD accelerates cardiovascular risk.
Abstract 10946: Myocardial Inflammatory Activity and Oxidative Stress Immunosuppressive Therapy Are Associated With Prognosis in Patients With Cardiac Sarcoidosis
Circulation, Volume 146, Issue Suppl_1, Page A10946-A10946, November 8, 2022. Background: Patients with cardiac sarcoidosis (CS) have been shown to be at an increased risk of major adverse cardiovascular events (MACE). Enhancement in myocardial inflammatory activity and oxidative stress is a crucial cause of MACE. Immunosuppressive therapy is recommended for the treatment of active CS. After immunosuppressive therapy, however, there is no predictable markers for prognosis. We hypothesized that the inflammation and oxidative stress in heart were associated with MACE.Aim:We identified prognostic markers for MACE in patients with CS after steroid therapy.Methods:This prospective cohort study enrolled 103 consecutive patients with CS diagnosed according to the Japanese guideline; Of 103 CS patients, 39 patients underwent 18F-FDG PET/CT 6 months after steroid therapy, and levels of urinary 8-hydroxy-2′-deoxyguanosine (U-8-OHdG) as a marker of oxidative DNA damage, other biomarkers, indices of cardiac function, and renal function were measured. Then they were followed up for a median of 42 months. The primary endpoint was a composite of the first sustained ventricular tachycardia (sVT) /sudden cardiac death (SCD), hospitalization for heart failure, and worsening CS with increased accumulation of FDG in heart and exacerbation of clinical manifestation.Results:During the follow-up period, 7 of 30 patients showed sVT/SCD (N= 9), hospitalization (N= 2) and worsening CS (N= 4). A Cox proportional-hazard model showed that U-8-OHdG concentration and SUV max value of FDG-PET were independent predictors of MACE. ROC analysis showed that the cut-off values of U-8-OHdG and SUV max for predicting the MACE were 14.2 ng/mg·Cr and 4.6 respectively. Patients with a U-8-OHdG ≥ 14.2 ng/mg·Cr or SUV max ≥4.6 had a significantly higher MACE risk (Figure A and B).Conclusions:U-8-OHdG and SUV max after steroid therapy were powerful predictors of MACE in CS, suggesting that CS patients with high U-8OHdG and/or high SUV max might be resistant to steroid therapy.
Abstract 10218: Differences in Treadmill Exercise Stress Testing Parameters Among Electronic Cigarette Vapers, Combustible Cigarette Smokers, and Controls: The Clues Study
Circulation, Volume 146, Issue Suppl_1, Page A10218-A10218, November 8, 2022. Background:Use of electronic nicotine delivery devices is increasing but their effects on exercise function are not well-characterized. We hypothesized that treadmill stress test outcomes would differ between chronic electronic cigarette users (“vapers”), combustible cigarette users (“smokers”), and non-smoking/non-vaping controls.Methods:CLUES (HL1393301) was a cross-sectional study of 395 individuals: 164 exclusive vapers (exhaled carbon monoxide [CO] 5 ppm, positive urine NicCheck I), and 114 non-vaping/non-smoking controls (CO
Abstract 13293: Albuterol and Hyperthyroidism as Potential Causes of Stress Cardiomyopathy
Circulation, Volume 146, Issue Suppl_1, Page A13293-A13293, November 8, 2022. IntroductionTakotsubo cardiomyopathy (TCM) is a recognized reversible process associated with emotional or physical stressors characterized by left ventricular apical ballooning in the absence of obstructive coronary artery disease. We present a unique case of TCM after albuterol use in the setting of hyperthyroidism.ResultsA 74-year-old woman with history of hyperthyroidism and asthma presented with acute substernal chest pain and progressive dyspnea. She was diagnosed with an asthma exacerbation, started oral prednisone 3 days before presentation, and reported using 16 puffs of her albuterol inhaler the day before. Examination revealed blood pressure 157/100 mmHg, heart rate 135 beats per minute, respiratory rate of 35 breaths per minute, and SpO2 94% on a 5-liter nasal cannula. Lung exam revealed bilateral end-expiratory wheezes, and she appeared in respiratory distress. The remainder of the exam was unremarkable, including cardiac exam. ECG revealed atrial tachycardia with ST elevations in the anterolateral leads concerning for injury. High sensitivity troponin was 1484 ng/L (ref
Abstract 12932: Should We Screen For Radiotherapy-Induced Heart Disease With Exercise Stress Echocardiography? Emphasis on Major Adverse Cardiac Events
Circulation, Volume 146, Issue Suppl_1, Page A12932-A12932, November 8, 2022. Introduction:Exercise Stress Echocardiography (ESE) is recommended as a screening tool for the evaluation of Coronary Artery Disease (CAD) in patients with suspected Radiation-Induced Heart Disease (RIHD). Up to now, studies have only evaluated its association with the extent of CAD.HypothesisCancer survivors treated with chest Radiotherapy (RT) that undergo an ESE and have a +ESE develop more MACE than those who have -ESE.Methods:A retrospective, descriptive, cohort study was conducted. Patients who had chest RT and underwent ESE with Treadmill Bruce Stress Protocol, from 2000 to 2012, at Mayo Clinic Rochester and Mayo Clinic Health System were included. A univariate analysis was performed to characterize the population. An analysis including Kruskal Wallis and Pearson Chi-Squared tests was completed to identify variables associated with + SE (Table 1). Multivariable Cox Model for MACE was conducted and is shown in Table 2. A time-to-event curve using Kaplan-Meier estimates is shown in Figure 1.Results:We identified 113 patients, with a mean age of 67 years and a median follow-up of 15.1 years. Of those, 99% were female, 98% were breast cancer survivors, 59% had HTN, 14% DM, 11% AFib, 2% COPD, and 12% had a history of MI. All the patients received >3000cGy of Photon RT, and 57% were treated with systemic cancer therapies. A +ESE was seen in 20.3% of the patients with no significant difference in METS achieved compared with patients who had a -ESE. COPD, RT dose, and systemic therapies, specifically doxorubicin, were associated with a +ESE. The cumulative incidence of MACE was higher in the group of +ESE (p=0.029). After adjustment for HTN, DM, smoking history, hyperlipidemia, and prior MI, the HR for MACE associated with a +ESE was 1.97 (1.09-3.59).Conclusion:MACE was more frequent in patients with a +ESE who received chest RT and doxorubicin versus -ESE. These results support the usefulness of ESE in cancer survivors after RT as a cardiovascular screening tool.
Abstract 13156: The Location of Combined High-Risk Low Endothelial Shear Stress and High Plaque Structural Stress is Distant From the Minimal Lumen Area in the Majority of Coronary Plaques Responsible for Major Adverse Cardiac Events
Circulation, Volume 146, Issue Suppl_1, Page A13156-A13156, November 8, 2022. Introduction:The presence of multiple high-risk prognostic features enhances risk-stratification of plaques prone to destabilization and major adverse cardiac events (MACE). Spatial superimposition of high-risk features (concordance) likely amplifies local risk. Local endothelial shear stress (ESS) and plaque structural stress (PSS) metrics predict MACE, but their spatial concordance and their location relative to the minimal lumen area (MLA) is unknown. If the highest-risk plaque area is distant from the MLA, then PCI of the MLA alone will leave high-risk plaque areas untreated.Purpose:To identify the site of high-risk features of low ESS and high PSS heterogeneity (HI) along the course of a plaque in patients who develop MACE, and the site of their spatial concordance relative to the MLA.Methods:We examined ESS, PSS, and PSS HI in 22 non-culprit lesions (NCL) leading to MACE, and 64 randomly selected control NCLs without MACE from the PROSPECT study. ESS was calculated by computational fluid dynamics and PSS by finite element analysis on co-registered lesions. We examined high-risk plaques with empirically-derived (ROC curve) ESS < 1.3 Pa and PSS HI > 0.29 in 16 lesions leading to future MACE, and 11 control lesions without MACE.Results:MACE outcomes were significantly more frequent in plaques with combined low ESS+high PSS HI vs plaques with low ESS alone (72.7% vs 27.3%, p
Abstract 15056: Cardiac P62/sqstm1 Deficiency Exacerbates Hypoxic Stress via Impaired Hypoxia Inducible Factor 1α Signaling
Circulation, Volume 146, Issue Suppl_1, Page A15056-A15056, November 8, 2022. Ischemic heart disease (IHD), a major cause of heart failure, is characterized by metabolic dysfunction and myocardial cell death. Cellular hypoxia activates hypoxia inducible factor 1α (HIF1α) to initiate metabolic, angiogenic, and growth-factor related responses. Under normoxia, HIF1α is degraded by prolyl hydroxylase (PHD) domain-containing proteins via the proteasome. Due to the short half-life of HIF1α (
Abstract 15067: Stress Hyperglycemia on Hospital Admission Drives the Risk of Re-Hospitalization for Chest Pain in INOCA Patients
Circulation, Volume 146, Issue Suppl_1, Page A15067-A15067, November 8, 2022. Introduction:Ischemia with non-obstructive coronary arteries (INOCA) is a relatively new condition, often observed in patients with angina. However, the exact pathophysiology of INOCA is not fully understood, and its management remains very debated.Hypothesis:We hypothesized that admission hyperglycemia in INOCA patients could be associated with the risk of being re-hospitalized for chest pain.Methods:We evaluated INOCA patients referred to our Institution between 2016 and 2021 for percutaneous coronary intervention (PCI). We divided our population in quintiles according to the values of the stress hyperglycemia ratio (SHR), calculated as the ratio of admission blood glucose (expressed as mmol/L) and HB1Ac (%). We calculated Kaplan-Meier product limits for cumulative ratio of reaching the endpoint and we applied the log-rank test. To further confirm our results, we performed a multivariable analysis in order to adjust for potential confounders.Results:2874 INOCA patients were enrolled in our study. At 1-year follow-up, the risk of hospitalization for chest pain was progressively higher in patients with higher SHR values (p
Abstract 15165: Dobutamine Stress Echocardiography in Patients With Low Flow, Low Gradient Aortic Stenosis and Preserved Lvef
Circulation, Volume 146, Issue Suppl_1, Page A15165-A15165, November 8, 2022. Introduction:Guidelines recommend the use of Dobutamine stress echocardiography (DSE) in case of low flow low gradient aortic stenosis (LFLG AS) when left ventricular ejection fraction (LVEF)
Abstract 12919: Stress Induced Cardiomyopathy After the Covid-19 Vaccine
Circulation, Volume 146, Issue Suppl_1, Page A12919-A12919, November 8, 2022. Introduction:The SARS-CoV-2 virus has potential to cause acute and long-term cardiac effects. The vaccines were developed to prevent severe illness, but there are concerns about vaccine related side effects. Specific to the heart there have been case reports of mRNA vaccine related cardiomyopathies, particularly myocarditis. We present a case of a patient with presumptive stress induced cardiomyopathy in the setting of recent Covid-19 mRNA vaccination.Case Presentation:A 93-year-old female with a past medical history of hypertension presented with worsening shortness of breath and bilateral lower extremity edema. She received her second dose of the Covid-19 mRNA vaccine five days prior to presentation. She had no history of heart disease, was a nonsmoker, and denied alcohol or drug use. In the ED she was noted to be fluid-overloaded, and her CT chest showed minimal coronary calcification and bilateral pleural effusions. She was admitted for heart failure exacerbation and started on IV furosemide. Her transthoracic echocardiogram showed an ejection fraction of 40-45%. The pattern of left ventricular dysfunction was consistent with stress induced cardiomyopathy with apical akinesis and basal sparing of the left ventricular wall segments. Cardiology was consulted and recommended management with diuretics and beta blocker. She had a diuresis of 5 liters during her hospitalization. At clinic follow-up, dyspnea had improved, and her peripheral edema had resolved. Repeat echocardiogram showed recovery of left ventricular ejection fraction to 61% by Simpsons biplane technique with no regional wall motion abnormalities. Further cardiac assessment to evaluate for obstructive coronary artery disease and myocarditis was discussed and offered to the patient but was declined due to her positive response to conservative management.Discussion:The precise etiology of stress induced cardiomyopathy is unknown, but it is thought to be secondary to the sudden release of stress hormones. There are isolated reports of stress induced cardiomyopathy associated with Covid-19 vaccination, but the potential mechanism is unclear. An improved understanding of the potential effects of mRNA vaccines may help guide decisions regarding future booster vaccinations.
Abstract 11394: The Yield of Stress Myocardial Perfusion Imaging in Patients With Chest Pain and Low Pretest Probability of Coronary Artery Disease
Circulation, Volume 146, Issue Suppl_1, Page A11394-A11394, November 8, 2022. Introduction:Chest pain is a common presentation in the emergency department and physician office visits. Identifying coronary artery disease (CAD) as the cause of chest pain is essential for improving prognosis. The 2021 AHA/ACC guidelines do not advocate for testing in patients with low pretest probability (PTP