Abstract 14699: Effect of Shear Stress on Arterial Inflammation and Development of Healed Plaque: A Comprehensive Shear Stress-Molecular Imaging Study Based on a Novel Multispectral Fluorescence Lifetime Imaging Catheter

Circulation, Volume 146, Issue Suppl_1, Page A14699-A14699, November 8, 2022. Introduction and Hypothesis:Endothelial shear stress (ESS) is the tangential force produced by luminal blood flow on arterial endothelium. Both high ESS and low ESS are known to have atherogenic effects, however, it remains poorly understood how these different forces influence coronary atherosclerosis. We evaluated the impact of ESS changes on biochemical and phenotypic difference of coronary atheroma, as assessed by a novel dual-modal optical coherence tomography-fluorescence lifetime imaging (OCT-FLIm)in vivoin beating human coronary arteries.Methods and Results:We constructed a fully-integrated OCT and multispectral FLIm system based on a low-profile dual-modal imaging catheter. High-speed OCT-FLIm could be performed safely in patients undergoing coronary revascularization (Pullback speed: 10-20mm/sec). 3D artery model for computational fluid dynamics was reconstructed by fusion of OCT and angiography. We analyzed spatial associations between ESS and multispectral FLIm information: ch.3(542nm) = fibroatheroma with inflammation; ch.1 (390nm) = loose fibrous tissue (healed plaque). OCT-FLIm visualized coronary microstructure clearly and offered correctly-coregistered biochemical readouts of coronary atherosclerotic plaquein vivoin a label-free manner. Fibroatheromas with increased inflammation activity, as assessed by ch.3 FLIm, were found in low ESS area. On the other hands, high ESS area colocalized with regions with increased ch.1 lifetime, a FLIm signature of loose fibrous tissue (healed plaque). Based on a coregistered ESS-FLIm data, we found a statistically significant negative correlation between ESS and ch.3 lifetime (p >0.001) and a positive correlation between ESS and ch.1 lifetime (p >0.001).Conclusions:Low ESS was associated with lipid and macrophage infiltration whereas high ESS was associated with presence of loose fibrous tissue, a histologic marker of recent plaque disruption leading to rapid plaque progression. Our novel imaging strategy enabling comprehensive evaluation of complex interaction between ESS and biochemical phenotype of plaques is expected to enhance understanding of coronary atherosclerosis biology.

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Ottobre 2022

Abstract 13332: Obesity Paradox in Stress Cardiomyopathy When Comparing Outcomes

Circulation, Volume 146, Issue Suppl_1, Page A13332-A13332, November 8, 2022. Introduction:Stress Cardiomyopathy (SCM), is an acute reversible myocardial injury associated with transient left ventricular dysfunction. Risk factors include female sex, post-menopause, anxiety, depression, schizophrenia, asthma and chronic obstructive pulmonary disease, diabetes, and substance use. Obesity has an increased sympathetic tone and state of chronic metabolic stress, both of which are similar in etiology to SCM. We postulate that obesity may have high prevalence in patients with SCM.Methods:We queried the Nationwide Inpatient Sample database (2016-2019) to identify adult patients with SCM with and without obesity, along with other common co-morbidities using ICD-10 codes. We compared the categorical and continuous variables by Pearson χ2 and Student t test.Results:There were 31,725 patients with SCM. The mean age was 67.15+14 years and the population was predominately female, n=26409 (83.2%). Racial distribution consisted of White (n=24713 77.9%), Black (n=24713, 8%), and Hispanic (n=1918, 6%). There were 3816 (12%) who were diagnosed with obesity. When comparing both groups, obese patients were found to be younger than non-obese, 63.3+14 years vs. 67.68+13 years, p

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Ottobre 2022

Abstract 9608: Upregulation of Cardiac Beta3-Adrenergic Receptor-Activated iNOS Uncoupling Promotes Diabetic Cardiomyopathy in Type II Diabetic Mice: Role of Oxidant Stress

Circulation, Volume 146, Issue Suppl_1, Page A9608-A9608, November 8, 2022. Background:Recent evidence highlights oxidative stress as an important mechanism to cardiac dysfunction in type 2 diabetes (T2D) and altered β3-adrenergic receptor (AR)-activated nitric oxide synthase (NOS) pathway contributing to this process. However, the NOS isoforms involved are controversial. The mechanism of how β3-AR stimulation impacts ROS, SERCA2a, and cardiac function in T2D is unclear. We tested the hypothesis that oxidant stress from upregulation of LV β3-AR-activated iNOS uncoupling promotes T2D cardiomyopathy.Methods:We compared myocyte β1- and β3-AR, NOS, peroxynitrite (NT), NADPH and SERCA2a expressions and myocyte functional responses to β- and β3-AR stimulation with isoproterenol (ISO,10-8M) and BRL-37344 (BRL,10-8M), respectively, in the absence and presence of iNOS inhibitor, 1400W (10-5M) of female mice over 14 weeks (W): 7 normal and 7 with T2D induced by 14 W high-fat diet (HFD) intake, but after HFD for 4 W receiving streptozotocin (STZ, 40 mg/kg/day, i.p. 5 days).Results:Versus normal myocytes, T2D myocytes had significantly increased protein levels of β3-AR (0.25 vs 0.14) and iNOS (0.25 vs 0.15) accompanied with increased oxidative stress indicated by significantly-elevated NT formation, NADPH (P67-phox, 33% and p22-phox, 29%) and decreased GTPCH expression (0.43 vs 0.85) and activity. T2D myocytes had significantly decreased β1-AR (0.35 vs 0.49) and SERCA2a (0.19 vs 0.29). These changes were associated with reduced cell contraction (dL/dtmax, 75.4 vs 133.7 μm/s), relaxation (dR/dtmax, 59.6 vs 113.8 μ m/s), and [Ca2+]iT(0.16 vs 0.21) accompanied by diminished β-AR-stimulated positive inotropic response, but enhanced β3-AR-induced negative inotropic response. Only in T2D myocytes, pretreatment with 1400W improved basal cell function and augmented ISO-increased dL/dtmax(64.5%) and [Ca2+]iT(29.2%), but significantly limited BRL-induced decrease in dL/dtmax(12.7%) and [Ca2+]iT(9.8%).Conclusions:T2D is associated with contrasting changes on myocyte β1- and β3-AR expression with decreased SERCA2a and increased iNOS. Upregulation of β3-AR triggers iNOS uncoupling, leading to oxidative stress, thus promoting intrinsic myocyte dysfunction with impaired [Ca2+]iregulation and reduced β-AR reserve.

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Ottobre 2022

Abstract 15081: The Viscoelastic Yield Stress of Blood is Negatively Associated With Pulmonary Blood Flow in the Fontan Circulation

Circulation, Volume 146, Issue Suppl_1, Page A15081-A15081, November 8, 2022. Introduction:In the Fontan (FN) circulation pulmonary blood flow (Qp) is passive, resulting in severely decreased shear rate and velocity in pulmonary arteries to the point of stasis. Yield stress (YS) is the shear stress required for blood to transition from stasis to a moving fluid. Therefore, YS may be a determinant of Qp in FN. We evaluated YS in patients with FN and Glenn (GLN) circulations and whether increased YS is associated with decreased Qp.Methods:We enrolled 20 patients with biventricular (2V) congenital heart disease (CHD) and 41 patients with single ventricle CHD (19 FN and 22 GLN) who were undergoing a clinically indicated cardiac catheterization. Two patients were excluded due to pulmonary vascular disease. We obtained blood samples at the time of catheterization and measured blood viscosity across shear rates 1 s-1to 1000 s-1using a Rheolog viscometer We calculated YS by curve-fitting of the viscosity measurements to a Casson fluid model.Hypothesis:We hypothesize that higher yield stress will be associated with lower pulmonary blood flow in Fontan circulation.Results:The FN group was the oldest and had the largest BSA (FN >2V >GLN; pFN >2V; p

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Ottobre 2022

Abstract 9504: Endothelial Shear Stress Metrics Correlate With Inflammatory Markers at the Culprit Site of Erosion in Patients With an Acute Coronary Syndrome: An OPTICO-ACS Substudy

Circulation, Volume 146, Issue Suppl_1, Page A9504-A9504, November 8, 2022. Introduction:The pathobiological mechanisms of coronary plaque erosion are unclear. Low endothelial shear stress (ESS) is a proinflammatory/proatherogenic stimulus associated with coronary plaque progression/destabilization. Intravascular imaging studies suggest that high ESS gradient (low ESS areas adjacent to high ESS areas), and steepness of plaque upslope/downslope correlate with plaque erosion. We investigated the relationship of local fluid hemodynamics to the inflammatory microenvironment at the culprit site of erosion in patients with an acute coronary syndrome.Hypothesis:ESS metrics associate with proinflammatory/proatherogenic cells and cytokines, and contribute to plaque erosion.Methods:We studied 30 patients with erosion from the OPTIcal-COherence Tomography in Acute Coronary Syndrome study (OPTICO-ACS). OCT images were segmented, co-registered with the angiogram to create a 3D-reconstruction of the coronary artery. ESS metrics were calculated by Computational Fluid Dynamics. Systemic and local blood samples and thrombectomy specimens were collected at the culprit lesion and analyzed by flow cytometry-based immunophenotyping and plasma cytokine and chemokine profiling, and statistically tested for correlations of continuous variables using Spearman rank correlation (r).Results:Proinflammatory cytokines (IL6, MIP-1, IL1β, IL2) and local concentration of T-cells, including subsets of T-cells (CD4+, CD8+, and NKT-cells), were significantly higher at the culprit site of erosion and correlate with local adverse ESS metrics (Min ESS, Max ESS, Plaque Topographical Slope) (Table).Conclusion:Biomechanical features likely trigger activation of the adaptive immune system, including T-lymphocytes and their cytotoxic effector molecules. These results provide novel insights into the links between fluid hemodynamics, inflammatory activation, and mechanisms involved in the pathogenesis of coronary plaque erosion.

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Ottobre 2022

Abstract 14606: Accurate Detection of Acute Psychological Stress Events Using Single Lead ECG Data

Circulation, Volume 146, Issue Suppl_1, Page A14606-A14606, November 8, 2022. Introduction:Stress has been linked to numerous health conditions, including heart disease, diabetes, and mental health issues. By monitoring changes in physiological signals, such as heart rate (HR) and heart rate variability (HRV), wearable biosensing technology allows acute stress to be non-invasively tracked over long periods, providing valuable insights for preventative healthcare.Methods:This two-phase study comprised several protocols designed to induce varying levels of psychological stress in participants (N=39). HR and HRV metrics, derived from electrocardiogram (ECG) data collected throughout the protocol on the single lead HeartKey®Chest Module, were used by the HeartKey Stress algorithm to generate a relative stress score (0-100), which was validated against two clinically recognized methodologies for assessing patient stress: i) state-trait anxiety index (STAI), a questionnaire that subjectively measured the individual’s perceptual stress after each stage of the protocol, and ii) electrodermal activity (EDA), which continuously monitored conductive changes at the skin’s surface with an Empatica®E4 wrist wearable.Results:Over both phases, participant STAI scores increased significantly during stress protocols (49.9 ± 23.3) relative to the baseline (30.0 ± 10.0). Mean HR showed a similar significant increase (p< 0.001), and HRV gradually decreased throughout the testing protocol. HeartKey Stress scores derived from HR and HRV data showed a strong correlation to STAI scores. Furthermore, the HeartKey Stress trend closely replicated that of the EDA data.Conclusions:HeartKey Stress algorithm consistently generated accurate and reliable stress scores in response to events of induced, acute psychological stress. The results suggest that the algorithm has potential utility for continuous clinical monitoring of patients with stress-related illnesses.

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Ottobre 2022

Abstract 10038: Combined Low Endothelial Shear Stress and High Plaque Structural Stress Heterogeneity Predicts Non-Culprit Major Adverse Cardiovascular Events; Insights From the PROSPECT Study

Circulation, Volume 146, Issue Suppl_1, Page A10038-A10038, November 8, 2022. Introduction:Low endothelial shear stress (ESS) is a pro-atherogenic stimulus associated with coronary plaque development, while high plaque structural stress (PSS) and its heterogeneity is associated with plaque destabilization. Previous studies showed that combining ESS and PSS additively predicts plaque progression, but no studies have determined their ability to predict major adverse cardiovascular events (MACE). We examined whether combining ESS and PSS improves MACE prediction in patients with acute coronary syndrome.Methods:We examined baseline ESS, ESS gradient, PSS, and PSS heterogeneity index (HI) in 22 non-culprit lesions (NCL) leading to future MACE, and 64 randomly selected control NCLs without MACE from the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. ESS was calculated by computational fluid dynamics and PSS by finite element analysis on co-registered lesions.Results:86 lesions (55 thin-cap and 31 thick-cap fibroatheromas) were analyzed from 67 patients. Lesions that caused future MACE showed baseline higher PSS HI (0.32 vs. 0.24, p

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Ottobre 2022

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.

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Ottobre 2022

Abstract 14748: Genetic and Neurobiological Factors Link Chronic Stress to Earlier Onset Hypertension

Circulation, Volume 146, Issue Suppl_1, Page A14748-A14748, November 8, 2022. Introduction:Chronic stress conditions associate with a greater incidence of hypertension (HTN).Hypothesis:We tested whether genetic risk for or neurobiological features of vulnerability to chronic stress associate with the risk for and timing of HTN.Methods:Data were obtained from Mass General Brigham Biobank participants. HTN was defined as >2 International Classification of Disease codes at least one week apart. Those with secondary HTN and those diagnosed at age

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Ottobre 2022

Abstract 11502: Exercise Stress Testing for Arrhythmic Mitral Valve Prolapse

Circulation, Volume 146, Issue Suppl_1, Page A11502-A11502, November 8, 2022. Background -Mitral valve prolapse (MVP) is a common valvular abnormality found in approximately 2.4% of the population. Whereas the majority of cases are benign, an increasingly recognized sequela of MVP is sudden cardiac death (SCD), but triggers and risk factors for SCD are not well-defined. It is theorized that increased stretch on the papillary muscles due to MVP leads to papillary muscle fibrosis and cellular changes of local conduction properties, increasing the risk of ventricular arrhythmias and SCD.Hypothesis- We hypothesized that patients with MVP and SCD would have increased ventricular arrhythmias and ECG changes compared to MVP controls during exercise stress testing.Methods -The study population was generated from the Duke Epic. Patients were included if they had guideline-based diagnosis of MVP on echocardiogram or cardiac magnetic resonance imaging. Increase in ventricular arrhythmias during exercise was defined as >/= 10 PVCs per minute, multifocal PVCs, or >/= 2 PVCs in a row.Results-A total 2,513 patients with MVP were screened. 18 patients with SCD. Patients with SCD were younger [(47.22 +/- 12.2 ) vs. (58.0 +/- 18.7), p=0.02], more likely to be female (89.9% vs 64%, p=0.04) and had increased rate of bileaflet prolapse (72% vs. 40%, p=0.01) compared to controls. Patients with sudden cardiac death had either dynamic T wave changes or increased ventricular arrhythmias with stress testing versus controls [12/18 (66.7%) vs 17/75 (22.6%), p

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Ottobre 2022

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.

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Ottobre 2022

Abstract 13149: Mental Stress-Induced Hemodynamic Changes and Cardiovascular Outcomes

Circulation, Volume 146, Issue Suppl_1, Page A13149-A13149, November 8, 2022. Introduction:Hemodynamic responses to mental stress (MS) have been associated with adverse CV outcomes. We investigated if hemodynamic responses during laboratory MS testing are predictive of outcomes.Hypothesis:Lower rate pressure product (RPP) changes during MS testing are predictive of adverse CV events.Methods:Patients recruited into the Mental Stress Ischemia Prognosis Study and Myocardial Infarction and Mental Stress Study 2 studies underwent MS testing with a standardized public speaking stressor and followed for incident CV death, MI rates (primary endpoint) and heart failure hospitalizations (secondary endpoint). Maximum changes in the RPP during MS were calculated. A generalized linear mixed model determined predictors of RPP change, and Prentice, Williams, Peterson model gap time approach was used for analysis of recurrent events after adjustment for demographic and clinical variables.Results:In 919 patients (mean 59.6 years; 65.6% men), the median change in RPP was 5,112 mmHg x beats/minute (IQR, 3,666 – 7,120). Patients with lower RPP changes (

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Ottobre 2022

Abstract 10098: Assessment of a Rate Pressure Product Target During Stress Echocardiograms in Patients With Advanced Cirrhosis

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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Ottobre 2022

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

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Ottobre 2022

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

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Ottobre 2022

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.

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Ottobre 2022