Abstract 13902: Using a Proteomics-Based Cardiovascular Risk Test to Identify Systemic Changes in a Clinical Trial of Nonalcoholic Fatty Liver Disease

Circulation, Volume 148, Issue Suppl_1, Page A13902-A13902, November 6, 2023. Background:Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular outcomes. Assessment of the impact of NASH therapy on cardiovascular risk is an important element of NASH drug development but is challenging particularly in early phase trials. Aptamer-based proteomic profiles (Somalogic®) in serum have been used to develop and validate a risk score as a surrogate for cardiovascular (CV) risk.Hypothesis:Improvement in NASH histology will result in improved proteomic cardiovascular risk scores.Methods:A post-hoc analysis of proteomic profiles of serum samples, using the Somalogic® platform, from the Pioglitazone vs. Vitamin E vs. Placebo for Treatment of Nonalcoholic Fatty Liver Disease (PIVENS) trial was conducted. PIVENS was a 96-week trial of nondiabetic participants with (NASH). We applied the proteomic CV risk scores to samples from baseline, on therapy and end of treatment visits (n=7) visits and received liver histology results at baseline and 96 weeks on N = 209 (84.6%) study participants. Generalized linear and mixed models were used to assess the association between CV risk score, treatment arm and change in liver biopsy results.Results:Baseline scores were similar across groups (mean 0.19, SD 0.14). There was no association between treatment arms and changes in scores during therapy and end of treatment. However, improvement in histological markers of activity (lobular inflammation and NAFLD activity score) and fibrosis were associated with improved cv risk scores (Figure) (p< 0.05 for all).Conclusions:Improvement in hepatic inflammation, NAFLD activity score and fibrosis were associated with improved proteomic CV risk scores regardless of treatment provided. Additional prospective validation of these findings is warranted. Proteomic profiling can potentially be used to track changes in cardiovascular risk profile changes in response to therapy in the short term NASH treatment trials.

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Novembre 2023

Abstract 16196: E/e' Predicts Exercise Capacity in Participants Undergoing Exercise Stress Test

Circulation, Volume 148, Issue Suppl_1, Page A16196-A16196, November 6, 2023. Introduction:The ratio of early transmitral flow velocity (E) to early diastolic mitral annular velocity (e’) is a surrogate for left ventricular (LV) filling pressure. Post-stress E/e’ has been shown to predict exercise capacity, but few studies have investigated this correlation with baseline E/e’. Our aim was to evaluate the relationship between baseline E/e’ and exercise capacity during stress test.Methods:All patients undergoing exercise stress testing at University of Virginia from 1/2015 through 9/2015 with the required echo data were included in this study. E/e’ was categorized into quartiles. ANOVA was used to evaluate the relationship between quartiles of E/e’ and exercise duration or METS. Multivariate linear regression was used to adjust for the variables: age, sex, ejection fraction, systolic blood pressure, heart rate, and regional wall motion abnormalities.Results:Baseline characteristics of the 312 participants based on E/e’ quartiles are shown in Table 1; those with higher E/e’, on average, had higher baseline SBP, were older, and had a higher percentage of females. There was a significant difference in exercise duration and METS between E/e’ quartiles (Table 2A) [p < 0.001]. There was an inverse correlation between E/e’ and exercise capacity; the significance was more pronounced with increasing E/e’ (Table 2A) and was present even after adjusting for multiple covariates (Table 2B).Conclusions:Baseline E/e’ correlates with exercise capacity (both duration of exercise and total METS achieved). This suggests that elevated LV filling pressures at rest can predict exercise capacity and may be targeted in future studies to improve exercise tolerance.

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Novembre 2023

Abstract 15645: Budget Impact Analysis of PrecisionCHD, an Artificial Intelligence Guided, Integrated Genetic-Epigenetic Test for Assessing CHD, Demonstrates Extensive Cost Savings Compared to Conventional Methods

Circulation, Volume 148, Issue Suppl_1, Page A15645-A15645, November 6, 2023. Coronary heart disease (CHD) costs the United States healthcare system at least $216 Billion in treatment cost and $147 billion in lost productivity annually. Therefore, there is an urgent need for cost-effective solutions to reduce both the human and economic burden of CHD. Because the initial CHD diagnostic approach has a large impact on subsequent costs and healthcare outcomes, risk bearing entities are keen to determine the optimal algorithmic approach for guiding the use of CHD diagnostic tools. In order to better understand the economic and clinical impact of a newly developed Precision Epigenetic test for assessing CHD status, PrecisionCHD, we conducted a budget impact analysis comparing the use of PrecisionCHD to the use of conventional exercise ECG and coronary computed tomographic angiography (CCTA) (in a 75:25 ratio) as the initial diagnostic assessment of CHD using nationally published cost estimates, generally accepted side effects, sensitivity and specificity metrics for each test, with all positive tests resulting in the initiation of moderate to high dose statin therapy as per treatment guidelines. Our analysis showed that for an insurance plan with 1 million covered individuals, a $20 co-pay for office visits and 10% co-insurance, the use of PrecisionCHD over exercise ECG and CCTA would result in $92 million in annual cost savings with a significant portion of those savings being secondary to the inferior performance of exercise ECG. Increasing the number of CCTA test performed increases the number of CHD cases detected, but also results in greater costs including costs secondary to contrast dye induced kidney damage. We conclude that the use of PrecisionCHD for CHD detection can improve healthcare outcomes and decrease CHD related costs. Given current trends in the developments in epigenetics-based approaches, it is likely that this advantage will increase further.

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Novembre 2023

Abstract 16973: Using an in-vitro and ex-vivo Test Platform for Evaluation of a Pen-Sized Ultrasound Vascular Access Device (Vu-Path)

Circulation, Volume 148, Issue Suppl_1, Page A16973-A16973, November 6, 2023. Introduction:Despite several off-the-shelf ultrasound systems being used for large vessel access, reliable and safe vascular access remains a problem. This is especially true during combat casualty care where skilled operators may not be available. We tested a novel small-footprint platform for efficacy and timeliness of large vessel access at normovolemic and hypovolemic statesHypothesis:A custom-designed device with optimized ergonomics and workflow will yield high success rates and low training needs for large vessel accessMethods:Vu-Path has a pen-size 10 mm ultrasound transducer with a proprietary needle guide and a lightweight engine deployed with a tablet or laptop. The display has an overlay showing the needle insertion path. Once the vessel is visible within the overlay, insertion of the needle using the needle guide directs insertion to the vessel. We used 3 models to simulate femoral vessel access: 1) a commercially available phantom (CAE Blue Phantom); 2) a custom in-vitro tissue phantom mimicking swine normovolemic and hypovolemic femoral vascular states; 3) an ex-vivo model of a euthanized swine lower-body section with canulated femoral vessels looped with a peristaltic pump to simulate normovolemic and hypovolemic states.Results:Vu-Path tested in these 3 models resulted in 87% successful insertions across all models and conditions; 100% success on the commercial model versus 83% in the custom tissue phantoms. In every model, 2 metrics were evaluated as summarized in Figure: total time to align vessel in the needle track window, and total time after aligning to confirmed insertion. Mean attempts needed to gain system expertise was 6.Conclusions:Vu-Path had high success rates for vessel visualization and needle access guidance in 3 models simulating normovolemic and hypovolemic conditions. Training requirements were minimal. These data suggest Vu-Path is capable of potentially improving safety and reliability of large vessel access.

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Novembre 2023

Abstract 12748: Continuous Measurement of Percutaneous Oxygen Saturation During 6-Minute Walk Test is Useful for Predicting the Prognostic Risk in Patients With Heart Failure

Circulation, Volume 148, Issue Suppl_1, Page A12748-A12748, November 6, 2023. Background:The 6-minute walk test (6MWT) is an established test to assess functional exercise performance and the 6-minute walk distance (6MWD) is strongly correlated with the functional capacity and the prognosis in patients with heart failure (HF). However, the clinical implication of sequential changes in percutaneous oxygen saturation (SpO2) during 6MWT has not been investigated in HF patients.Purpose:To prospectively clarify the association between sequential changes in SpO2 during 6MWT and prognosis in patients with HF.Methods:Fifty patients admitted with acute heart failure were enrolled. The 6MWT was performed at the time before discharge, after hemodynamic stability was confirmed. The average of SpO2 was calculated from data obtained at rest and during 6MWT by employing the wearable pulse-oximeter which is designed to record the SpO2 value every second. Alternations in SpO2 (ΔSpO2) were obtained by subtracting the average during 6MWT from that at rest. Patients were followed up to 9 months for the composite outcome of heart failure-hospitalization and death.Results:The mean age of participants was 78.8 years, and 23 (46%) were female. The mean EF was 46.1% and the number of patients with EF ≦40 was 22. The 6MWD was 250 ± 112m and the ΔSpO2 was 2.88 ± 4.3%. All cases were classified by walk distance and ΔSpO2; long- ( >220m) vs. short-distance group (≦220m) and low- (

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Novembre 2023

Abstract 11520: Safety and Efficacy of Botulinum Toxin Type A for Prevention of Postoperative Atrial Fibrillation in Cardiac Surgery Patients: Pulmonary Function Test Results From the Phase 2 NOVA Study

Circulation, Volume 148, Issue Suppl_1, Page A11520-A11520, November 6, 2023. Background:Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Autonomic neuromodulation, including injection of botulinum toxin into epicardial fat pads, may suppress and/or attenuate atrial fibrillation. The respiratory safety of a potential preventative treatment for AF is critical.Aim:To assess efficacy and pulmonary safety of botulinum toxin type A (BoNT/A; AGN-151607) 125U and 250U vs placebo for prevention of POAF after coronary artery bypass graft and/or valve surgery.Methods:NeurOtoxin for the PreVention of post-operative Atrial fibrillation (NOVA; NCT03779841) was a phase 2, international, multicenter, randomized, placebo-controlled trial. The primary endpoint was proportion of patients with continuous AF ≥30 seconds within the first 30 days. Respiratory function was assessed via pulmonary function tests (PFTs) performed at baseline and day 30 after treatment. Adverse events (AEs), serious adverse events (SAEs), and time to extubation were recorded.Results:A total of 323 patients were randomized: BoNT/A 125U (n=106), 250U (n=109), placebo (n=108). The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125U group (relative risk [RR] vs placebo, 0.80 [95% CI: 0.58, 1.10];P=0.16), and 47.2% of the 250U group (RR vs placebo, 1.04 [95% CI: 0.79, 1.37];P=0.78). Baseline, day 30, and change from baseline PFT results were similar for active treatment vs placebo (Table). Median time to extubation was 9.7, 9.6, and 9.6 h in the placebo, 125U, and 250U groups, respectively. Respiratory AEs were reported in 42.9%, 38.1%, and 50.5% of patients, and respiratory SAEs in 11.4%, 6.7%, and 5.5% of patients in the placebo, 125U, and 250U groups, respectively.Conclusion:In this analysis of respiratory function, there appeared to be no detrimental effect of AGN-151607 compared with placebo, as evidenced by similar outcomes in PFT parameters and respiratory AE/SAE incidences among treatment arms.

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Novembre 2023

Abstract 13988: Post Stress Test High-Sensitivity Cardiac Troponin I in the Evaluation of Patients With Acute Chest Pain for Enhanced Ischemic Risk Assessment: A Pilot Study

Circulation, Volume 148, Issue Suppl_1, Page A13988-A13988, November 6, 2023. Introduction:High-sensitivity cardiac troponin I (hs-cTnI) assays provide comparable diagnostic information that allow for better detection of myocardial injury. However, hs-cTnI release after cardiac stress testing and its potential utility for identifying inducible myocardial ischemia and risk-stratification are unclear.Aim:This pilot study examined integrating hs-cTnI biomarker testing into cardiac imaging stress testing to improve detection of inducible ischemia and aid in risk-stratification in patients with chest pain being evaluated for acute coronary syndrome (ACS).Methods:We prospectively enrolled 200 consecutive adult patients referred by the Emergency Room for cardiac stress testing for evaluation of possible ACS. A venous blood sample was collected between 0.5 and 2 hours post stress testing; cTnI concentrations were measured in-house by high sensitivity methods. Changes from pre-stress test hs-cTnI concentrations were calculated and association with outcome was explored using a logistic regression model.Results:Patient median age was 62 years, IQR 54-70; 49% were women. ACS known risk factors included hypertension 81.5%, cigarette smoking 49.5% and diabetes 33.5%. Median BMI was 31.63 kg/m2, IQR 27.24-35.84. Pre-stress test hs-cTnI median levels were 6 ng/L, IQR 5-9, for women (URL

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Novembre 2023

Abstract 11812: Cardiopulmonary Exercise Test and Atrial Fibrillation in Obstructive Hypertrophic Cardiomyopathy: A Study From Septal Myectomy Patients

Circulation, Volume 148, Issue Suppl_1, Page A11812-A11812, November 6, 2023. Background:Cardiopulmonary exercise test (CPET )is currently used to quantify functional limitation and to evaluate the indications for surgery among patients with hypertrophic cardiomyopathy (HCM). Patients with HCM often have atrial fibrillation (AF) and their relationship is not clear.Objective:To investigate the function limitation among HCM patients who meet indications for septal myectomy and the association between it and AF. Method: We reviewed 565 consecutive patients who underwent myectomy from February 2019 to October 2021, of which 212 did CPET and 24h Holter before surgery.Results:In this cohort (median age: 50.55(37.6-58) years; male: 126(59.4%); left ventricular outflow tract gradient (LVOTG)≥ 50 mmHg: 190(89.6%)), there was a severely impaired function (Peak Oxygen consumption (Peak VO2): 16.44 ± 4.02 ml/min/kg, adjusted Peak VO2%: 58.27%). Comparing different groups divided by Peak VO2, the lowest group was characterized by older age (58 vs 50 vs 43.9 years, p < 0.001), more female patients (57.7% vs 38% vs 25.7%, p < 0.001), higher NT-proBNP level (1299 pg/ml vs 1049 pg/ml vs 742.5 pg/ml, p = 0.004), and larger left atrial diameter (46.8mm vs 43.77 mm vs 42.71 mm, p < 0.001). The incidence of AF also significantly increased (30.98% vs 14.08% vs 7.14%, p < 0.001). Among various indicators of CPET, Peak VO2 showed the strongest correlation with AF (point-biserial correlation coefficient: -0.347, p < 0.001; 0.2279, p = 0.011; -0.2502, p < 0.001; for Peak VO2, ventilatory efficiency, and anaerobic threshold, respectively). Additionally, the incidence of AF decreased with increasing severity of obstruction (60% vs 33.3% vs 16.2% vs 7.1% among non-obstructive, 30≥maximum LVOTG < 50 mmHg, 50≥LVOTG < 100 mmHg, >100 mmHg patients, respectively, p = 0.001). In multivariate regression analysis adjusting for age, sex, BMI, and left atrial diameter, Peak VO2 and LVOTG remained independently associated with the development of AF (OR 0.854, 95% CI 0.743-0.973, p = 0.021 and OR 0.969, 95% CI 0.949-0.987, p = 0.002, respectively).Conclusions:CPET indicator, particularly PeakVO2, was independently associated with the occurrence of AF in eligible surgical patients with HCM. We also found that the higher extent of obstruction, the lower the incidence of AF.

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Novembre 2023

Abstract 12194: Clinical Application of Virtual Antiarrhythmic Drug Test Using Digital Twins in Patients Who Recurred Atrial Fibrillation After Catheter Ablation

Circulation, Volume 148, Issue Suppl_1, Page A12194-A12194, November 6, 2023. Introduction:We previously reported that a computational modeling-guided antiarrhythmic drug (AAD) test was feasible for assessing diverse AADs in patients with atrial fibrillation (AF). In this study, we took the virtual AAD test (V-AAD) in patients who took AADs after AF catheter ablation (AFCA).Hypothesis:Patients using an effective drug in the VAAD test will have fewer AF recurrences than patients using an ineffective drug.Methods:This single-center retrospective study included 246 patients (72.8% male, 60.7±10.2 years of age, 38.6% paroxysmal AF) prescribed AADs within 3 months after AFCA. Using realistic computational modeling, we evaluated the effects of five AADs (amiodarone, sotalol, dronedarone, flecainide, and propafenone; 2 doses for each drug). Clinical AADs (C-AAD) were chosen at the discretion of the physicians blinded to the V-AAD test. We defined the effective V-AAD as the V-AAD that terminated AF or converted AF to atrial tachycardia (AT) and the best V-AAD as the V-AAD that ended virtual AF the fastest. We compared AF recurrence rates after the AAD prescription depending on the results of the V-AAD test.Results:The ineffective and best V-AAD were administered in 64 (26.0 %) and 70 patients (28.5%). The recurrence rate within a year after using the ineffective, effective, and best V-AAD were 46.9%, 35.7%, and 25.7%, respectively (log-rank p=0.013). The recurrence rate within a year in patients with at least one V-AAD terminating AF and those without was 33.9% and 50.0%, respectively (log-rank p=0.034). The use of best V-AAD (OR 0.43, 95% CI [0.18-0.96]; p=0.042, vs. ineffective V-AAD) is an independent predictor of AF recurrence within a year of using AAD after AFCA.Conclusions:The digital twins-guided V-AAD test was feasible for evaluating the efficacy of multiple AADs in patients with AF who had a high chance of recurrence after AFCA. We need a prospective randomization study to assess the prediction power of the V-AAD test.

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Novembre 2023

Abstract 15449: Cardiopulmonary Best Abstract Award: Pausing Reveals Exercise-Induced Uncoupling: Exploring the Dynamics of RV-PA Coupling in the Six-Minute Walking Test

Circulation, Volume 148, Issue Suppl_1, Page A15449-A15449, November 6, 2023. Background:The six-minute walking test (6MWT) is a commonly used test for assessing the functional capacity of patients with pulmonary hypertension (PH), providing functional and prognostic information. Functional capacity depends on RV-PA coupling, the matching of right ventricular contractility to afterload. However, the dynamics of RV-PA coupling during the 6MWT have never been studied.Methods:We used a wireless hemodynamic monitoring system (CorLog, emka-medical, Germany) to continuously measure right ventricular pressure in 10 patients with PH (8 = group I, 1 = III, 1 = IV) during a 6MWT. We calculated right ventricular ejection fraction (RVEF) and Ees/Ea based on the pressure signal as shown in the figure (panel a). Dyspnea was evaluated using the Borg scale.Results:By analyzing the hemodynamic response during the 6MWT, we identified two patterns: 1) Improved/preserved coupling: Five patients exhibited an initial improvement in Ees/Ea and maintained coupling at least at the baseline level throughout the test, without requiring pauses. 2) Uncoupling associated with pauses: Five patients experienced a slight increase in Ees/Ea at the beginning, followed by a progressive loss of coupling and ejection fraction, necessitating pauses. During pauses, Ees/Ea values restored, enabling patients to resume walking. Patients of the second phenotype reported higher levels of dyspnea. The highest reported Borg score was 8 ± 0.9 vs. 4.6 ± 1.2 in the first group. Also, the covered distance was shorter in the second group (159 ± 64m vs. 288 ± 88m, p=0.03). Both groups showed differences in Ees/Ea (0.47 [0.46 – 0.57] vs. 0.34 [0.30 – 0.43], P=0.05) and RVEF (34 ± 4.1% vs. 28.5 ± 2.6%, P=0.03) at baseline, with Group One exhibiting superior values.Conclusion:This is the first investigation into the significance of RV-PA coupling in real-life exercise limitation and dyspnea during the 6MWT. Pauses observed during the 6MWT can serve as indicators of exercise-induced uncoupling.

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Novembre 2023

Abstract 16611: The Feasibility of Artificial Intelligence in Interpretation of the Treadmill Test

Circulation, Volume 148, Issue Suppl_1, Page A16611-A16611, November 6, 2023. Introduction:The treadmill test (TMT) is commonly used as a screening test to identify myocardial ischemia. The sensitivity of the TMT in diagnosing obstructive CAD was approximately 50%, with a specificity of approximately 90%. However, the challenge with TMT is the variability in interpretation.Hypothesis:We aimed to develop an Artificial intelligence (AI) to interpret TMT. The primary endpoint was the accuracy comparison between the initial assessment (of AI or cardiologist) for obstructive CAD.Methods:Out of a total of 800 TMTs performed on adults for any clinical indications in 2018-2020, Of these, we used 500 as training data, 200 as validation data, and 100 as test data. A one-dimensional convolutional block was applied to each of the 12 leads of the TMT, and then all the leads were concatenated to apply a dense layer, which was then trained to predict the presence of obstructive coronary artery disease. This deep learning model was developed based on convolutional neural networks (CNNs) using TensorFlow (Google, Mountain View, CA, USA) and Keras packages based on the Python language. TMT were simultaneously interpreted by an AI algorithm or by the cardiologist. This assessment was subsequently reviewed by blinded interventional cardiologist who provided a final report of obstructive coronary artery disease (CAD) with coronary compute tomography.Results:The mean age was 58.1 (20-78) years, 68% were male, and 33% had obstructive coronary artery disease (≥70% stenosis in at least one vessel). The performance of AI was compared with that of conventional TMT. Accuracy of AI model was comparable to cardiologist (0.720 vs. 0.680,p=0.845) F1 score was also similar between AI and cardiologist (0.440 vs. 0.384.p=0.845)Conclusions:Artificial intelligence is comparable to a cardiologist in the initial interpretation of the treadmill test. These approaches might be applicable to data obtained from wearable electrocardiography technologies during exercise.

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Novembre 2023

Abstract 16552: Coronary Vasomotor Response to Intracoronary Ergonovine Provocation Test According to the Severity of an Insignificant Coronary Artery Fixed Stenosis

Circulation, Volume 148, Issue Suppl_1, Page A16552-A16552, November 6, 2023. BACKGROUND:Coronary artery spasm (CAS) is a major cause of variant angina in patients with chest pain without significant coronary stenosis. However, whether there are differences in the incidence of CAS according to the severity of underlying coronary artery fixed stenosis is limited.Methods:A total of 608 patients without significant coronary artery disease (CAD) who underwent the ergonovine (ERG) provocation test between January 2018 and December 2021 were enrolled. Significant CAS was defined as having≥70% of temporary narrowing by ERG test. Patients were divided into three groups, based on the presence of coronary artery stenosis: None group (n=456), mild group (30-49%,n=114) and moderate group (50-69%,n=38).Results:In patients with chest pain without significant coronary artery stenosis, mild stenosis was 18.8%, and moderate stenosis was 6.3% in the population. The baseline characteristics of the patients were worse in the mild and moderate group than in the None group, including age, hypertension, diabetes, and smoking habit. In the ERG test, CAS occurred in 44.4% (270/608) of the overall population. The incidence of CAS of the mild (55.3%) and moderate (52.6%) groups were higher than the None group (41.0%). Also, in the case of CAS occurrence, focal CAS (Length

Leggi
Novembre 2023

Association between plant-based or animal-based dietary pattern and plasma glucose during oral glucose tolerance test among Chinese women with gestational diabetes mellitus: a prospective cohort study

Objective
This study explored whether plant-based and animal-based dietary patterns are associated with plasma glucose levels during oral glucose tolerance test in women with gestational diabetes mellitus (GDM).

Design
A prospective cohort study was conducted using a Food Frequency Questionnaire to collect dietary data. Dietary patterns were derived using principal component analysis. Multivariate logistic regression analysis was performed to explore the association between dietary patterns and plasma glucose levels. Stratified analyses were conducted according to maternal age, prepregnancy body mass index (BMI) and other confounders.

Setting and participants
The study, conducted in January 2022 in two hospitals in Fujian, China, involved 424 women diagnosed with GDM using a 75 g 2-hour oral glucose tolerance test at 24–28 gestational weeks.

Results
Six maternal dietary patterns (plant based and animal based) were identified. Participants with plant-based pattern had lower 2-hour plasma glucose levels than those with animal-based pattern (β=–0.314; 95% CI (–0.596 to –0.032)). After adjusting the regression model covariates, this significant association remained (β=–0.288; 95% CI (–0.568 to –0.008)) and appeared more pronounced in women aged 30 years or above and those with prepregnancy BMI

Leggi
Ottobre 2023