bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13538: Associations Between Circulating Liver Enzymes and Platelet Reactivity
Authors: Nkambule Bongani , Chan Melissa V , Lachapelle Amber , Grech Joseph , Thibord Florian , Cuhna Jason , Pashek Robin , Chen Ming-Huei , Johnson Andrew D
Published: June 2023

Introduction:
The liver plays an essential role in thrombopoiesis and coagulation, and circulating liver enzymes are associated with altered platelet counts. However, the role of liver enzymes in the modulation of platelet reactivity remains unclear.

Methods:
A total of 3,429 Framingham Heart Study participants were included in this study. Platelet reactivity to 8 agonists, including adenosine diphosphate (ADP), thromboxane A
2
mimetic (U46619) and arachidonic acid (AA), was measured using light transmission aggregometry (LTA), Multiplate impedance aggregometry and Optimul aggregometry. Platelet counts and platelet-red blood cell aggregates were enumerated using flow cytometry. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also measured. Associations of platelet reactivity phenotypes with liver circulating liver enzyme levels analyzed using linear mixed-effects models and adjusted for sex, age, relatedness, smoking, aspirin-, and statin-use. To correct for multiple testing, a Bonferroni-correction threshold of P<0.0011 was used to account for multiple comparisons.

Results:
Higher ALT levels were associated with platelet disaggregation in LTA to ADP (β=0.056, SE=0.02, P=3.54E-04), and with decreased platelet reactivity in response to U46619 in Optimul (EC
50
: β=0.064, SE=0.019, P=7.65E-04). Interestingly, higher AST levels were associated with decreased platelet counts (β=-0.082, SE=0.019, P=1.04E-05), platelet reactivity to U46619 (β=-0.069, SE=0.018, P=1.04E-04) and AA (β=-0.047, SE=0.013, P=3.12E-04), and circulating platelet-red blood cell aggregates (β=-0.062, SE=0.018, P=9.54E-04).

Conclusion:
Our findings suggest that ALT levels could alter primary platelet aggregation. AST may indirectly modulate platelet counts. In addition, lower AST levels may contribute to platelet hyperresponsiveness. Lastly, ALT and AST levels may have antagonistic effects on the formation of platelet and red blood cell aggregates, which may indirectly influence platelet margination within vessels. Additional studies are underway to examine whether liver fat, a marker of fibrosis associated with cardiovascular disease, is also associated with altered platelet function.
Abstract 13540: Characteristics of Home-Based Walking Exercise Interventions Associated With Greater Improvement in Walking Performance in Peripheral Artery Disease: A Post-Hoc Analysis of the HONOR Randomized Clinical Trial Results
Authors: Cetlin Madeline , Zhang Dongxue , Tian Lu , Zhao Lihui , McDermott Mary M
Published: June 2023

Introduction:
Benefits of home-based exercise (HBE) interventions in lower extremity peripheral artery disease (PAD) are variable. This post-hoc analysis of the HONOR randomized trial studied characteristics of a home-based exercise intervention associated with greater 6-minute walk improvement in PAD.

Methods:
HONOR was a multi-centered randomized trial. PAD participants were randomized to either a HBE intervention or usual care for 9 months. The intervention consisted of four weekly in-person visits with an exercise coach followed by 16 telephone coaching calls over the next eight months. Participants were asked to walk for exercise five days/week, wear a Fitbit to monitor activity, upload their Fitbit on the study website, and visit the website at least weekly to view their exercise goals and monitor their progress toward exercise goals. The primary outcome was change in 6-minute walk distance at 9-month follow-up.

Results:
Of 200 people randomized (age 70 yrs. ±10.4, 52.5% female, 50% Black), 182 (91%) completed nine-month follow-up. Overall, the exercise intervention did not improve 6-minute walk compared to usual care [+5.5 vs. +14.4 m respectively (Mean diff: –8.9 m, 95% CI, –26.0, +8.2 m, P = .31)]. Among the 99 people randomized to HBE, change in 6-minute walk ranged from -239.2-233.7. See table for characteristics associated with greater six-minute walk improvement.

Conclusion:
In a home-based exercise intervention for PAD, more frequent use of the intervention website and greater exercise sessions/week, but not more time wearing a Fitbit, were associated with greater 6-minute walk improvement. Future home-based exercise interventions for PAD should help patients self-monitor exercise behavior and increase exercise sessions per week.
Abstract 13544: A Naturally-Derived Spirulina Peptide Reduces the Deleterious Vascular Effects of Hyperglycemia Regulating the DPP-IV Activity and LPCAT1
Authors: Carrizzo Albino , Sommella Eduardo , Di Pietro Paola , Damato Antonio , Sala Marina , Venturini Eleonora , Campiglia Pietro , vecchione carmine
Published: June 2023

Introduction:
Recently, we showed that administration of SP6 was able to exert an antihypertensive effect by enhancing endothelial vasodilation by promoting increased serum nitrite levels. New computational data revealed that SP6 is able to interact with the dipeptidylpepdase IV (DPP-IV) enzyme prompting us to hypothesize its possible involvement in the control of diabetes mellitus.

Hypothesis:
This work aimed to investigate the anti-diabetic role of the peptide SP6 isolated from gastro-intestinal-simulated in vitro digestion of spirulina platensis matrix.

Methods:
We used an experimental mouse model of type 2 diabetes. A 4-week treatment by gavage administration of SP6 was performed. By molecular biology studies and the use of mass spectrometry imaging (MALDI-MSI), the expression of GLUTs levels, DPP-IV activity and GLP-1 levels, and oxidative stress were evaluated.

Results:
We were able to show that daily oral administration with SP6 peptide was able to protect against hyperglycemia-induced endothelial dysfunction. Moreover, SP6 in vivo treatment was able to regulate the expression levels of GLUT1, GUT2, GLUT4 and SGLT2. In parallel, SP6 treatment was able to inhibit DPP-IV activity by promoting an increase in circulating levels of glucagon-like-peptide 1 (GLP1). Measurement of glycated hemoglobin levels after a 5-week treatment period showed that peptide treatment was able to normalize HbA1c levels, bringing its levels back below 6% and to modulate lysophosphatidylcholine and Phosphatidylcholine levels.

Conclusions:
In conclusion, our data support the beneficial role of SP6 on the pathophysiology of diabetes and lay the foundation to develop a novel anti-diabetic strategy.
Abstract 13550: Electrocardiographic-Based Artificial Intelligence Model in Prediction of 1-year Mortality in Heart Failure With Reduced Ejection Fraction
Authors: Lee Hak Seung , Kang Sora , Jang Jong-Hwan , Jo Yong-Yeon , Son Jeong Min , Lee Min Sung , Kwon Joon-Myoung
Published: June 2023

Objectives:
To assess whether electrocardiography (ECG)-based artificial intelligence (AI) algorithm developed to detect 1-year mortality in patients with HF with reduced ejection fraction (HFrEF).

Methods and results:
Data from two hospital visits (2016 Oct to 2021 Apr) was used. Participants with good quality baseline ECGs and HFrEF were included. We tested the hypothesis that the application of AI to the ECG could identify 1-yr mortality in HFrEF patients. A total of 16,228 (64% male, mean age of 58.5) were eligible. When tested on an independent set of 16,228 patients, the network model yielded values for the area under the curve, sensitivity, specificity, and accuracy of 0.83, 83.3%, and 64.2%, respectively (
Figure a
). Those with a positive AI screen were at 2.6 times the risk (p<0.0001) of developing future mortality compared with those with a negative screen (
Figure b
). We used a sensitivity map to visualize the ECG region used in the AI model to detect high 1-yr mortality in HFrEF (
Figure c
). The map shows that the AI model focused on the QRS complex, particularly the R-wave, in most patients.

Conclusions:
The application of AI to the ECG permits the ECG to serve as a powerful screening tool for detecting 1-yr mortality in HFrEF.

Figure a.
The area under the curve of the convolutional neural network used to identify 1-year mortality of heart failure with reduced ejection fraction.

Figure b.
Long-term incidence of mortality in patients with initially 1-year mortality stratified by artificial intelligence classification.

Figure c.
Sensitivity map of a deep learning model for detecting 1-year mortality in heart failure with reduced ejection fraction.
Abstract 13567: Impact of Mavacamten on Artificial Intelligence Electrocardiographic Diagnosis of Hypertrophic Cardiomyopathy in the EXPLORER-HCM Trial
Authors: Siontis Konstantinos C , Barrios Joshua P , Attia Zachi I , Abreau Sean A , Abraham Theodore P , Olivotto Iacopo , Oreziak Artur , Barriales-Villa Roberto , Masri Ahmad , Lakdawala Neal K , Agarwal Priyanka , Balasubramanyam Aarthi , Sehnert Amy J , Friedman Paul A , Olgin Jeff E , Noseworthy Peter A , Tison Geoffrey H
Published: June 2023

Introduction:
Deep-learning artificial intelligence (AI) algorithms can identify hypertrophic cardiomyopathy (HCM) from the electrocardiogram (ECG). Preliminary data indicate that AI-ECG may also track treatment response in HCM patients (pts) receiving mavacamten (Mava). In this placebo-controlled analysis, we investigated the performance of AI-ECG in HCM detection and its changes during Mava treatment compared to placebo in the phase 3, EXPLORER-HCM trial.

Methods:
Pts with non-paced ECGs enrolled in EXPLORER-HCM, evaluating Mava over 30 weeks of treatment, were included. All pts had a 12-lead ECG pre-treatment, at each study visit, and 8 weeks after treatment end. Two independently developed AI-ECG convolutional neural network algorithms from the Mayo Clinic and the University of California, San Francisco (UCSF) were applied to all ECGs suitable for analysis. Serial AI-ECG-predicted scores, which correlate with HCM likelihood (range 0-1), were examined between Mava and placebo groups.

Results:
A total of 101 Mava and 110 placebo pts were included (mean age 58.6, female 40%). At baseline, the mean Mayo and UCSF AI-ECG scores for HCM were 0.82 and 0.65, with 94% and 88% of pts exceeding the respective diagnostic thresholds of 0.11 (Mayo) and 0.4 (UCSF). During 30 weeks of follow-up in the Mava group, the algorithms showed a mean AI-ECG score reduction of 0.32 (Mayo) and 0.17 (UCSF) in all pts between start and end of treatment. In comparison, AI-ECG scores decreased by 0.05 (Mayo) and increased by 0.02 (UCSF) in the placebo group (Mava vs placebo, t-test p-values <0.001 for both algorithms;
Figure
)

Conclusion:
In the EXPLORER-HCM trial population, two independent deep-learning AI-ECG algorithms correctly identified most HCM pts and demonstrated significant reductions in predicted HCM scores after treatment with Mava when compared to placebo. This relative normalization of the ECG suggests disease-modifying properties of Mava, deserving further investigation.
Abstract 13575: Utilizing Electronic Health Record Alerts to Increase Prescription of Lipid Lowering Therapies in Patients Admitted With Acute Coronary Syndromes
Authors: Brummel Kent , Zimmerman Christopher , Madigan Michael , Stein Adam , Brandt Eric , Sukul Devraj , Adie Sarah
Published: June 2023

Introduction:Patients who present to the hospital with acute coronary syndromes (ACS) often have poor control of cardiac risk factors. Multiple studies have demonstrated that lipid lowering therapy is not appropriately initiated or intensified in these patients.Hypothesis:We hypothesized that an interruptive alert delivered via the electronic medical record would increase the initiation and intensification of lipid lowering therapies.MethodsUsing Epic EHR (Epic Systems, Verona, WI), an interruptive alert was designed to trigger upon opening the patient’s chart when the patients were admitted with an ICD code that indicated an ACS (i.e., STEMI, NSTEMI, or Unstable Angina). The alert included an order set to obtain a cholesterol panel or if a cholesterol panel had already been collected it would be displayed and suggest modifications to the patient’s current medication regimen. These alterations included statin intensification or the addition of ezetimibe.ResultsBetween September 1, 2021 and May 30, 2022 172 unique patients were identified. The mean age was 64.8 ±13.8 years, 64.5% were male, 74% were white, and 12% were black. The identified patients had multiple comorbidities including cerebrovascular disease (23%), heart failure (47%), peripheral vascular disease (30%), and being a current or former smoker (53%). The triggered order set had a direct effect on 42 (24%) patients, with 10 initiating ezetimibe and 32 having their statins intensified. The most common indicated reason for overriding the alert (n=99) was not meeting criteria. Of these 99 patients, 4 were ultimately started on ezetimibe, 57 had their statin intensified, and 23 were appropriately excluded (including patients with type II myocardial infarctions who were not the target of this intervention). Of note, 15 patients should have received intensified therapy but had their alert over ridden.ConclusionsThis targeted alert led to direct intensification of lipid lowering therapy in 24% of ACS patients with an additional 35% of patients identified by the alert also having therapeutic intensification. This alert will remain in place to allow for further assessment of its effects and can be easily translated to other clinical systems.
Abstract 13582: Biomarkers of Adverse Cardiovascular Events in Chronic Coronary Disease: Data From the ISCHEMIA Trial
Authors: Newman Jonathan D , Ruggles Kelly V , Cornwell Macintosh , Anthopolos Rebecca , Held Claes , Kullo Iftikhar J , Newby L Kristin K , McManus Bruce M , Bangalore Sripal , Reynolds Harmony R , Hochman Judith S , Maron David J , Berger Jeffrey S
Published: June 2023

Introduction:
Circulating biomarkers may improve prediction of cardiovascular (CV) events in chronic coronary disease (CCD). The incremental value of biomarkers in CCD after adjustment for clinical factors, inducible ischemia and coronary artery disease (CAD) severity is uncertain.

Methods:
756 ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) participants with site-determined moderate-severe ischemia and 9 assayed biomarkers (Figure) were included. Among participants with interpretable stress tests for ischemia and CAD by computed coronary tomography angiography (CCTA) (N=507), associations of biomarkers with the primary (CV death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) or secondary endpoints (CV death or MI) were evaluated using sequentially adjusted multivariable Cox proportional hazards models (Model 1=unadjusted, Model 2=clinical features, Model 3=Model 2 + multivessel CAD by CCTA, and Model 4=Model 3 + severe ischemia).

Results:
Median (IQR) participant age was 64 (57-70) years, 19% were female, 81% white, and 5% Hispanic. Hypertension (85%), diabetes (46%) and obesity (45%) were common, 28% had an estimated glomerular filtration rate <60 ml/min/1.73m
2
. Severe ischemia was present in 44%, and 39% had multivessel CAD (≥70% stenosis) by CCTA. Over 3.5 (2.4-4.7) years of follow-up there were 146 (19%) primary and 128 (17%) secondary endpoints. Soluble CD40L, GDF-15, NT-proBNP, hsTnT were associated with the primary and secondary endpoints in univariable and multivariable (adjusting for clinical features, multivessel CAD and severe ischemia) models.

Conclusion:
Biomarkers of inflammation (GDF-15), thrombosis (sCD40L), myocardial stretch (NT-proBNP) and injury (hs-troponin) were associated with CV endpoints in the ISCHEMIA trial independent of clinical features, multivessel CAD and severe ischemia.
Abstract 13587: A Prior History of Myocarditis Increases Risk of COVID-19-Related Myocarditis
Authors: VAELI ZADEH ALI , Wong Alan , Zachariah Ashvin , Collado Elias , Larned Joshua
Published: June 2023

Background:
Viral myocarditis (MC) is an uncommon inflammatory condition of the myocardium. Its pathogenesis is postulated to involve a combination of direct virus-induced cardiomyocyte injury and immune-mediated cell death that results in fibrosis, dilated cardiomyopathy, arrhythmias, and heart failure. Studies indicate an increased incidence of MC in association with COVID-19 infection. However, the risk factors for COVID-19-related MC remain unknown or debated. This study sought to examine the association between a prior history of MC and COVID-19- related MC.

Methods:
Using ICD-10 codes, a cohort of patients admitted between March-August 2020 with the primary diagnosis of COVID-19 was identified from the PearlDiver database (PearlDiver Technologies, Fort Wayne, IN). The cohort was divided into two groups based on prior history of all-cause MC. To determine the incidence of MC, both groups’ records were searched in the 60-day period after admission. We used Pearson's chi-squared test to compare the MC frequencies between groups. Results were reported as Risk Ratios (RR) with 95% CI. A p-value <0.05 was deemed significant.

Results:
We identified 439,172 admissions with COVID-19. Of this cohort, 914 (0.208%) had at least one episode of MC before admission. Patients with a history of MC were younger (mean age 56, SD 19 vs. 60, SD 16), mostly male (54%), with more comorbidities (Elixhauser Comorbidity Index = 9 vs. 6) . Two months after hospitalization, 756 (0.17%) of COVID-19 patients developed MC. The risk of MC was 8.31% among patients with a history of MC and 0.16% among those without. The risk of COVID-19-related MC was significantly higher in patients with a prior history of all-cause MC (RR = 53.59, 95% CI = 42.66-67.31, p<0.0001)

Discussion:
According to our findings, patients with a history of MC are significantly more likely to develop COVID-19-related MC. A proposed mechanism could be that previously injured cardiomyocyte may be expressing higher levels of ACE2, which allows SARS-CoV-2 to enter. Our results help in risk stratification based on a history of MC.
Abstract 13607: Myocardial Tissue Characterization by Contrast-Enhanced Cardiac Magnetic Resonance Imaging in Patients With Combined Diabetes Mellitus and Obstructive Sleep Apnea
Authors: Silva Thiago Q , Bakker Jessie , Baltzis Dimitrios , Chan Raymond H , Manning Warren J , Wallace Meredith , Gongora Carlos , Gilman Hannah , Sama Supraja , Nikolaidou Sofia , Sposito Andrei , Coelho-filho Otavio R , Hudson Margo , Jerosch-Herold Michael , Veves Aristidis , Malhotra Atul , Patel Sanjay , Neilan Tomas G
Published: June 2023

Introduction:
Overlap of type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) increases the risk of heart failure possibly mediated by myocardial fibrosis.

Hypothesis:
T2DM+OSA overlap increases myocardial fibrosis.

Methods:
This was a prospective study where 141 participants (Control: 28; T2DM only: 27; OSA only: 29; T2DM+OSA: 57) underwent a sleep study and cardiac magnetic resonance. The measures of interest were LV and RV extracellular volume (ECV), native T1 and cardiomyocyte size (tau). Differences were tested with Kruskal-Wallis. The groups 'T2DM only' and 'OSA only' were combined (Control; T2DM or OSA; T2DM+OSA) for trend analysis with Jonckheere-Terpstra test.

Results:
Groups had similar sex [Control (males): 54%; T2DM: 44%; OSA only: 52%; T2DM+OSA: 65%; p=0.31)]; OSA and OSA+T2DM participants were older (46± 15; 51±7.8; 53±10; 56±9.1*
#
years; respectively p=0.001; *p<0.05 vs. control,
#
p<0.05 vs. T2DM only) and had higher BMI (29.8±6.3; 31±4.8; 34±6.3*; 35.2±6.6*
#
kg/m
2
, respectively p=0.001). LV ECV increased progressively with highest values among subjects with T2DM and OSA (0.25±0.02%; 0.27±0.03%; 0.28±0.04%; 0.31±0.05%; respectively, p=0.001; p for trend<0.001). LV native T1 was similar across groups (995±91 ms; 986±112 ms; OSA: 977±132 ms; 1041±128 ms; respectively, p=0.39; p for trend=0.14), and the T2DM+OSA group had a marginally higher LV tau (0.15±0.04 s; 0.13±0.05 s; 0.12±0.04 s; 0.17±0.06 s; respectively, p= 0.05; p for trend=0.59). RV ECV (0.40±0.06%; 0.41±0.05%; 0.40±0.04%; 0.42±0.05%; respectively, p=0.70; p for trend=0.27) and RV native T1 (1105±164 ms; 1083±124 ms; 1063±189 ms; 1092±148 ms; p=0.85; p for trend=0.85) were similar. RV tau was similar but with a positive trend towards T2DM+OSA (0.087±0.029 s; 0.094±0.023 s; 0.990±0.033 s; 0.115±0.045 s; p= 0.17, p= 0.03).

Conclusions:
The overlap of T2DM and OSA has an incremental adverse effect on the LV ECV and may explain the increased risk of adverse cardiac events.
Abstract 13622: Effect of Dapagliflozin and Saxagliptin Combination on CD34+ve Endothelial Progenitor Cells (EPCs) in Type 2 Diabetes Subjects
Authors: Nandula Seshagiri R , Elzarki Adrian , Sen Sabyasachi
Published: June 2023

Introduction:
We examined the effect of Dapagliflozin (Dapa) and Dapagliflozin-Saxagliptin combination (Combo) on EPCs in Type-2-Diabetes (T2DM) subjects as a cellular cardiovascular biomarker. Both Dapa (a SGLT2 receptor inhibitor) and Saxagliptin (a DPP4 enzyme inhibitor) are T2DM medications, but the combination has not been evaluated for cardiovascular outcomes, using stem cells.

Hypothesis:
We hypothesized that Dapa will improve EPC number and function compared to placebo and Combo may have additional positive effects.

Methods:
In this pilot study, 15 subjects were enrolled in 16 weeks, double-blind, randomized placebo matched trial, with 3 arms: 10mg
Dapa
+ Saxa placebo (n=4), 10 mg Dapa + 5 mg Saxa (n=5)
Combo,
And Dapa placebo + Saxa placebo (n=6),
Placebo
groups. T2DM (30-70 years) and HbA1c of 7-10%, were included. HbA1C between 7 to 8 was maintained. Peripheral blood derived CD34+ EPC number, migratory function, mRNA gene expression along with arterial stiffness, biochemistry, resting energy expenditure, and body composition were measured. Data were collected at weeks 0, 8, and 16. A mixed model regression analysis was done with a p-value <0.05 considered significant.

Results:
A significant decreased glucose (p=0.0317) and HbA1c (p=0.0357) levels were noted in Combo group compared to Dapa and more so compared to Placebo. hsCRP levels (P=0.0317)) are significantly reduced in both Dapa and Combo (to a similar extent) vs Placebo. The LDL/HDL ratio is significantly reduced (p=0.05) in combination group as compared to either Dapa alone or Placebo group. Leptin levels decreased significantly in both Dapa alone (p=0.035) and Combo group(p=0.015) , to a similar extent vs Placebo. EPC migration improved significantly in both Dapa alone (p=0.05) and Combo group (p=0.05) , to a similar extent, vs Placebo. Both Serum IL-6 levels and IL6-mRNA expression on EPCs showed significant reduction in both Dapa and Combo (to a similar extent) vs Placebo.

Conclusions:
Our study indicates that several parameters showed significant differences of Dapa and Combo when compared to placebo. However, other than glycemic control the Combo did not offer any further benefit over Dapa alone as far as inflammatory markers or stem cell number or migration properties were concerned.
Abstract 13625: Autophagy Plays a Key Role in the Loss of Nitric Oxide Signaling and Endothelial Dysfunction in Pulmonary Vascular Diseases
Authors: Liang Ying , Ornatowski Wojciech , Lu Qing , Sun Xutong , Garcia Alejandro E , Zemskov Evgeny A , Maltepe Emin , Fineman Jeffrey R , Tieu Kim , Wang Ting , Black Stephen M
Published: June 2023

Introduction:
Congenital heart defects (CHDs) are the most common type of birth defect. Children or infants with CHD often develop pulmonary vascular diseases (PVD) due to increased pulmonary blood flow and pressure. Unfortunately, there is no effective therapy to limit the shared pathophysiologic features of pulmonary endothelial dysfunction and vascular remodeling. Autophagy, a lysosome-dependent proteolytic pathway, enables cells to sequester portions of cytosolic proteins or damaged organelles into autophagosomes and degrade them in autolysosomes. Studies have found that autophagy participates in pulmonary hypertension, acute lung injury, lung cancer, and other pulmonary diseases.

Hypothesis:
Autophagy plays a key role in the development of pulmonary endothelial dysfunction in PVD associated with CHD.

Methods and Results:
We utilized lung endothelial cells isolated from an ovine CHD model, created by the fetal placement of an aortopulmonary graft (Shunt). First, we confirmed that autophagy was activated in Shunt pulmonary artery endothelial cells (PAEC), with increased LC3-II/LC3-I ratio (1.45 fold increase, n=3, p<0.05) and reduced p62 levels (64% reduction, n=3, p<0.05). Shunt PAECs were found hyperproliferative (BrdU Assay A
450
: control
vs.
Shunt: 2.36 ± 0.05
vs
. 2.58 ± 0.05, n=9, p<0.01), which can be attenuated by pharmacologic autophagy inhibitor bafilomycin A1 (2.30 ± 0.05, n=9, p<0.01 compared with Shunt) or 3-MA (2.20 ± 0.03, n=9, p<0.001 compared with Shunt). Shunt PAECs exhibited significant endothelial Nitic Oxide Synthase (eNOS) uncoupling by BH4 reduction (31% reduction, n=3, p<0.01). Bafilomycin A1 reversed eNOS uncoupling in Shunt PAECs by BH4 restoration (2.1 fold increase, n=3, p<0.01), resulting in elevated cellular NOx level (1.8 increase fold, n=3, p<0.01). Mechanistically, this was dependent on increased levels of GTP cyclohydrolase I (GCH1) protein in Shunt PAEC.

Conclusions:
Enhanced autophagy plays a key role in the loss of NO signaling and endothelial dysfunction associated with CHD. We speculate that autophagy might be an effective therapeutic target for pulmonary vascular diseases.
Abstract 13630: Association Between Arrhythmia Burden During Clinical Exercise Testing and All-Cause Mortality
Authors: Taylor Jenna L , Medina-Inojosa Jose R , Chacin Suarez Audry , Medina-Inojosa Betsy J , Somers Virend K , Bonikowske Amanda R
Published: June 2023

Introduction:
Arrhythmias commonly occur during clinical exercise stress testing (EST), however there are limited data on prognostic significance, particularly differences between individuals with minor versus significant arrhythmia burden.

Hypothesis:
We hypothesized that significant but not minor arrhythmia burden during EST would be predictive of future all-cause mortality.

Methods:
Adults who underwent clinically indicated EST at Mayo Clinic Rochester between September 1993 and April 2017 were included and followed-up until March 2021 using the National Death Index to ascertain survival status. Expert clinician coding pertaining to arrhythmia burden during EST were used to group individuals (see
Table 1
). Cox proportional hazard models adjusted for known predictors of exercise-induced arrhythmias, were used to test the association of arrhythmia burden with all-cause mortality.

Results:
A total of 30796 individuals were included (age: 55±14yrs; female: 36%;
Table 1
). Mean follow-up was 8.8±3.6yrs, with a total of 2516 deaths. Arrhythmia during EST was associated with all-cause mortality compared with no arrhythmia (HR: 1.72; 95% CI: 1.58-1.88; p<0.001), however significant arrhythmia showed greater association compared with minor arrhythmia (HR: 2.07; 95% CI: 1.81-2.38; p<0.001). Both minor and significant arrhythmia during EST were significant predictors of all-cause mortality compared with no arrhythmia (
Figure, Table 2
), however, after model adjustments, only significant arrhythmia was associated with all-cause mortality (HR: 1.40; 95% CI: 1.21-1.63; p<0.001) (
Table 2
).

Conclusions:
After multivariate adjustment, significant arrhythmia burden during EST showed a 40% increased future risk of all-cause mortality, Conversely, adjusting for age and sex attenuated the effect of minor arrhythmia burden during EST on incidence of death. These results highlight the clinical significance of arrhythmia burden during exercise testing.
Abstract 13636: Persistent Acute Kidney Injury is Associated With Poor Outcomes and Increased Hospital Cost in Vascular Surgery
Authors: Hensley Sara , Filiberto Amanda , Adiyeke Esra , Ozrazgat-Baslanti Tezcan , Upchurch Gilbert R , Bihorac Azra , Cooper Michol
Published: June 2023

Introduction:
Postoperative acute kidney injury (AKI) is common after vascular surgery and is associated with increased morbidity and mortality.

Hypothesis:
It is hypothesized that patients with persistent postoperative AKI have increased complications, mortality and hospital cost.

Methods:
A single center retrospective cohort of patients undergoing non-emergent major vascular surgery (lower extremity bypass, endovascular and open aortic surgery), between 2014-2019 was analyzed. Development of postoperative AKI (defined as > 50% or 0.3 mg/dl increase in serum creatinine relative to reference after surgery and before discharge) was evaluated. Patients were divided into 3 groups: no AKI, non-persistent AKI (< 48 hours) and persistent AKI (
>
48 hours). Multivariable regression analyses were then used to evaluate the association between AKI status and postoperative complications, 90-day mortality, and hospital cost.

Results:
A total of 1,881 patients undergoing 1,980 vascular procedures were included. Thirty five percent of patients developed postoperative AKI. Patients with persistent AKI were more likely to have longer ICU and hospital stays, as well as more mechanical ventilation days. In risk-adjusted logistic regression analysis, persistent AKI was a major predictor of 90-day mortality (OR 4.4, 95% CI 2.5-7.6). Risk-adjusted average cost was higher for patients with any type of AKI. The incremental cost of having any AKI ranged from $5,500-$12,400, even after adjustment for comorbidities and other postoperative complications. The risk-adjusted average cost for patients stratified by type of AKI was higher among patients with persistent AKI compared to those with no or non-persistent AKI (Fig.1).

Conclusions:
Persistent AKI after vascular surgery is associated with increased complications, mortality and cost. Strategies to prevent and aggressively treat AKI in the perioperative setting are imperative to optimize care for this population.
Abstract 13652: A Randomised Double-Blind Placebo-Controlled Study of Fenofibrate as a Metabolic Modulator to Augment Cardiac Physiology in Moderate-Severe Aortic Stenosis
Authors: Monga Shveta , Valkovic Ladislav , Myerson Saul G , Neubauer Stefan , Mahmod Masliza , Rider Oliver J
Published: June 2023

Background:
Pressure overload in aortic stenosis (AS) is associated with reduced cardiac fatty acid oxidation (FAO) and evidence of myocardial steatosis and impaired myocardial energetics. Here, we investigated whether modulating myocardial metabolism to increase FAO with a PPARα agonist, Fenofibrate in moderate-severe AS had effects on cardiac metabolism and physiology.

Methods:
67 participants with asymptomatic moderate-severe AS were prospectively randomised (double-blinded) to receive either Fenofibrate 200mg once daily (N= 54) or placebo (N=13) for 6 months (180 ± 7 days duration). Follow-up data is available in 42 patients. Primary endpoint was reduction in myocardial triglyceride content (MTG) measured using proton magnetic resonance spectroscopy (MRS). Secondary endpoints included cardiac PCr/ATP measured by 31P-MRS and LV strain assessed using MR tagging.

Results:
There was significant reduction in MTG content (-0.40%, CI -0.74 to -0.06, p= 0.022), with a no significant reduction seen in placebo. (-0.46%, CI -1.1 to 0.17, p= 0.13). A significant increase in venous butyrate levels was seen in the fibrate group (+0.09 mmol/l, CI 0.006 to 0.17, p= 0.036) in line with increased fatty acid oxidation. No change in cardiac energetics was seen in either group. No change in cardiac function was seen in either group, global longitudinal strain (-0.07%, p 0.89 Fibrate vs -0.31%, p 0.67 Placebo), circumferential strain ( -0.15 %, p 0.80 Fibrate vs 1.71%, p 0.07 Placebo).

Conclusions:
Fenofibrate can potentially upregulate fatty acid oxidation in hypertrophied AS hearts reducing myocardial lipid content, but this did not have any measurable beneficial physiological effect in moderate-severe AS.
Abstract 13658: Impact of Risk Factors for Atrial Fibrillation on the Incidence of Stroke in African American Females
Authors: Yi Jin , Gharbin John , Elawad Ayman , Brgdar Ahmed , Yazdanpanah Fariba , TAHA Mohamed , Williams Deborah
Published: June 2023

Background:
It is well-known that African American (AA) patients with Atrial Fibrillation (AF) have a higher incidence of stroke in comparison to the general population. To our knowledge, limited data exist on gender disparities in risk factors contributing to a higher incidence of stroke among AA patients. The objective of this study is to identify gender disparities in risk factors for AF by comparing AA females and males with AF.

Methods:
AA patients aged 18 years old or above with a diagnosis of AF were included in this study. Patients were selected from the 2019 national inpatient sample. The primary outcome of interest was incidence of stroke. T-test was used to compare differences in continuous variables. For categorical variables, pearson chi-square was used to compare differences. Multivariate logistic regression was used to adjust for potential confounders. A 2-sided P<0.05 was considered significant throughout the analyses.

Results:
This study included 45,102 AA female patients with AF, and 46,768 AA male patients with AF. In our study, female patients had higher prevalence of Hypertension (HTN) (22.3% vs 19.0, P<0.001), Diabetes Mellitus (DM) (48.1 vs 46.0, P<0.001), Obesity (27.8 vs 20.8), Hyperlipidemia (HLD) (50.9% vs 49.1%, P<0.001), Hyperthyroidism (2.2% vs 1.2%, P<0.001), and Chronic Obstructive Pulmonary Disease (COPD) (24.8% vs 23.2%, P<0.001). AA female patients with AF experienced higher incidence of stroke compared to AA male patients with AF, (4.9% vs 4.1%, p-value <0.001) and the odds of stroke also showed higher in female patients (aOR=1.10, 95% CI: 1.03-1.18,
p
<0.005) after controlling for comorbidities. Only HTN and HLD showed statistically significant association with stroke in univariate analysis, (OR=2.02, 95% CI: 1.89-2.16 and OR=1.24, 95% CI:1.16-1.31, respectively)

Conclusion:
In our study, we identified that AA female patients with AF had a higher incidence of stroke compared to AA male patients with AF. Only HTN and HLD were significant risk factors contributing to the increased stroke incidence in the female group. The findings of our study are hypothesis-generating, and well-powered randomized controlled trials are needed to validate these findings.
Abstract 13661: An Adaptive Strategy of Predictive Enrichment to Increase Efficiency of Randomized Clinical Trials Using Machine Learning:
A Simulation of the IRIS Trial
Authors: Oikonomou Evangelos K , Suchard Marc A , Kernan Walter N , Young Lawrence H , Inzucchi Silvio E , Khera Rohan
Published: June 2023

Introduction:
Randomized controlled trials (RCT) represent the cornerstone of evidence-based medicine but often carry high financial costs and lengthy time frames.

Hypothesis:
We hypothesized that a machine learning (ML) strategy of predictive enrichment can reduce the size of RCTs through adaptive enrollment based on projected response profiles.

Methods:
We conducted a
post-hoc
analysis of individual patient data from the Insulin Resistance Intervention after Stroke (IRIS) trial using dynamic computational trial phenomapping. After a study period of 36 months, we performed serial annual interim analyses (
A
). For this, we designed an algorithm that used a phenotypic trial representation using 59 baseline variables to predict personalized effects of pioglitazone on fatal/nonfatal stroke or myocardial infarction (study outcome). Compared with a complete trial enrollment (100%), in an adaptive fashion, we
a priori
restricted enrollment to two thirds (66.7%) of eligible participants between each interim analysis based on the projected treatment benefit. Since this was defined by their baseline phenotypic profile, treatment randomization was preserved. We employed these patient subsets as comparators and assessed the effect of pioglitazone on the study outcome through Cox regression models.

Results:
Compared to the unrestricted enrollment of participants (

blue line

), an ML-guided adaptive strategy of predictive enrichment (

green line

) was associated with defining the same treatment effect size with a lower trial size - 3876 vs 2946 participants (
B-C
). Both approaches appeared to meet statistical significance at 6 years after the trial onset (
D-E
). In contrast, a strategy of random patient selection (

orange line

) did not show significant benefit at the same population size.

Conclusions:
We developed an adaptive strategy for predictive enrichment to increase efficiency of RCTs using machine learning.
Abstract 13662: The Role of Pcsk9 in Abdominal Aortic Aneurysm
Authors: Rhee Yae Hyun , Spin Joshua , Deng Alicia , Headley Colwyn , Tsao Philip S
Published: June 2023

Introduction:
Abdominal aortic aneurysm (AAA) is a local weakening and dilatation of the abdominal aorta ≥50%, is associated with high mortality in the event of rupture and has no current pharmacologic treatment. Proprotein convertase subtilisin/kexin type 9 (Pcsk9), an enzyme mainly known for its production in liver, can cause familial hypercholesterolemia due to gain-of-function mutations. When triggered by pro-inflammatory stimuli, Pcsk9 expression by vascular smooth muscle cells (VSMC) has been found to induce cellular polyploidy, senescence, and apoptosis, hallmarks of AAA. Further, our collaborative consortium identified a relationship between Pcsk9 variants and AAA disease in humans utilizing a genome-wide association stud
y
(GWAS) in the Million Veteran Program. Lastly, our transcriptional profiling experiments in the porcine pancreatic elastase (PPE) model of murine AAA found significant early (Day 3) upregulation of the Pcsk9 gene in aorta.Monoclonal Pcsk9 antibody therapies are effective for hypercholesterolemic patients who are resistant to conventional statin therapy. However, the role of Pcsk9 in AAA has not been explored in depth. If Pcsk9 were found to be pivotal in disease, Pcsk9-inhibitors could be high priority candidates for investigation in limiting AAA.

Methods:
Using the PPE model, AAA was induced in wildtype C57Bl/6 mice and Pcsk9 knock-out (KO) mice. Aneurysm growth was monitored via sonography at various time points, and local vascular Pcsk9 and inflammatory marker gene expression were measured by qPCR. In vitro, VSMC were treated with exogenous Pcsk9 and assayed for pro-inflammatory marker expression.

Results:
Sonographic imaging data showed smaller AAA diameters in Pcsk9 KO mice compared with wildtype C57Bl/6 mice. Inflammatory gene expression was significantly downregulated with Pcsk9 KO. In-vitro VSMCs showed upregulated inflammation after exogenous Pcsk9 treatment.

Conclusions:
Our data suggest that Pcsk9 plays a crucial role in the development of AAA and could be a viable treatment target to inhibit AAA progression.
Abstract 13665: Determination of Lipid-Rich Plaque by Artificial Intelligence-Enabled Quantitative Computed Tomography Using Near-Infrared Spectroscopy
Authors: Omori Hiroyuki , Matsuo Hitoshi , Earls James , Sobue Yoshihiro , Fujimoto Shinichiro , Nozaki Yui , Nakazawa Gaku , Takahashi Kuniaki , Osawa Kazuhiro , Okubo Ryo , Kaneko Umihiko , Sato Hideyuki , Kajiya Takashi , Miyoshi Toru , Ichikawa Keishi , Abe Mitsunori , Kitagawa Toshiro , Ikenaga Hiroki , Saji Mike , Iguchi Nobuo , Ijichi Takeshi , Mikamo Hiroshi , Kurata Akira , Moroi Masao , iijima raisuke , Crabtree Tami , Min James K , Nakanishi Rine
Published: June 2023

Introduction:
By near-infrared spectroscopy (NIRS), plaques with 4-mm maximum lipid-core burden index (maxLCBI4
mm
) ≥400 are lipid-rich plaques. By CCTA, high-risk plaques are defined by presence of low-density non-calcified plaque (LD-NCP) and positive remodeling (PR) >1.1.

Hypothesis:
Artificial intelligence-enabled quantitative CT (AI-QCT) will enable identification of lipid-rich plaques when compared to NIRS reference standard.

Methods:
128 atherosclerotic plaques from 47 patients were prospectively enrolled. MaxLCBI
4mm
(cutoff was defined as 400) and LD-NCP derived from AI-QCT (Cleerly LABS, Denver CO) were compared. We also analyzed vessel area, plaque burden, minimal lumen area and plaque length between intravascular ultrasound (IVUS) and AI-QCT.

Results:
Amongst 128 plaques evaluated, maxLCBI
4mm
≥400 was 26 plaques (20.3%). Use of current LD-NCP (<30 Hounsfield threshold (HU) and LD-NCP volume >0 mm
3
) and PR ≥1.1, yielded a sensitivity, specificity, positive and negative predictive value and accuracy of 100%, 28%, 26%, 99%, and 43%. LD-NCP volume

threshold was identified from AUC as 1.8 mm
3
. With LD-NCP volume

≥1.8 mm
3
, the performance of AI-QCT was improved to 92%, 87%, 65%, 98% and 88%, respectively (Figure 1). We noted very good to excellent correlation between AI-QCT and IVUS for vessel area (R2 =0.776), plaque burden (0.699), minimal lumen area (0.815) and plaque length (0.844).

Conclusions:
The current CCTA definition of NIRS-verified lipid-rich plaques has limited specificity and accuracy; use of a LD-NCP volume threshold, enabled only by AI-QCT, substantially improves performance for detection and characterization.
Abstract 13667: Coronary Artery Calcium for the Prediction of All-Cause and Cause-Specific Mortality Among Individuals With Obesity: The Coronary Artery Calcium Consortium
Authors: Boakye Ellen , Dardari Zeina A , Erhabor John , Osei Albert , Obisesan Olufunmilayo , Jha Kunal , Kumar Sant J , Rosanski Alan , Berman Daniel S , Budoff Matthew , Miedema Michael D , Nasir Khurram , Rumberger John A , Shaw Leslee J , Blaha Michael J
Published: June 2023

Introduction:
New therapies for obesity point to the need for greater risk stratification in this population. While the role of coronary artery calcium (CAC) for ASCVD risk prediction among key subgroups, e.g., those with intermediate ASCVD risk, is well established, the effectiveness of CAC for risk stratification in obesity, in which imaging is limited due to reduced signal-to-noise ratio, has not been well studied.

Methods:
We used data from 9,334 men and women (mean age 53.3 ± 9.7 years; 32.1% women) with BMI ≥30 kg/m2 from the CAC Consortium, a retrospectively assembled cohort of individuals with no prior CVD history referred for CAC scan. We categorized CAC as absent/present and 0, 1-99, 100-299, ≥300 AU. We then evaluated the predictive value of CAC for all-cause and cause-specific mortality (cardiovascular and CHD) using multivariable-adjusted Cox proportional hazard and competing risks regression, respectively.

Results:
Of the 9,334 participants, 5,461 (58.5%) had CAC. Compared to persons without CAC, those with CAC >0 had higher incidence of all-cause (5.65 vs 1.97 per 1,000 person-years), cardiovascular (1.89 vs 0.43 per 1,000 person-years), and CHD mortality (1.04 vs 0.19 per 1,000 person-years), after a mean follow-up of 10.8 ± 3.0 years. After adjusting for age, sex, and cardiovascular risk factors, individuals with CAC > 0 had significantly higher risk of all-cause (HR 1.39; 95%CI 1.07 - 1.80), cardiovascular (SHR 2.06; 95%CI 1.20 - 3.54), and CHD mortality (SHR 2.72; 95%CI 1.21 - 6.14), compared to those without CAC. Of note, CAC ≥300 was associated with a markedly higher risk of all-cause, cardiovascular, and CHD mortality, even when restricting to persons with ≥ Class II obesity (≥35 kg/m2) (Table)

Conclusions:
Among individuals with obesity, CAC strongly predicts all-cause, cardiovascular, and CHD mortality and may therefore serve as an effective risk stratification tool to prioritize the allocation of therapies for weight management in this population.
Abstract 13669: Ascending Aortic Augmentation Pressure Does Not Decrease During Exercise in HFpEF: Implications for SV Reserve Impairment
Authors: Wakeham Denis J , Bagga Joetsaroop S , Hughes Seamus B , Balmain Bryce N , Tomlinson Andrew R , Babb Tony G , Macnamara James P , Hearon Christopher M , Levine Benjamin D , Sarma Satyam
Published: June 2023

Aortic augmentation pressure (aAP; difference between first [aP1] and second [aP2] peaks of the aortic pressure waveform) decreases during exercise in young healthy individuals, lowering mid-late systolic afterload, an important determinant of cardiac work and stroke volume (SV). In patients with heart failure and preserved ejection fraction (HFpEF), SV responses to exercise (i.e. SV reserve) are often abnormal (≤ 50%). A lack of fall in aAP during exercise in HFpEF could contribute to impairments in SV reserve. Therefore, we studied 15 HFpEF patients (age, 71 ± 6 years; 10 women; BMI 39.2 ± 6.2 kg/m
2
) in the seated upright position. During rest and six-minutes of cycling at 20 Watts, we recorded beat-by-beat radial arterial blood pressure and estimated ascending aortic blood pressure waveforms in real-time via a generalized inverse transfer function (SphygmoCor). SV was calculated from cardiac output (Qc, acetylene rebreathe) and heart rate (ECG), with total peripheral resistance (TPR) calculated as the quotient of radial MAP and Qc. HR (Rest: 75 ± 14 vs 20W: 93 ± 12 bpm,
P
< 0.0001), SV (Rest: 61 ± 17 vs 20W: 84 ± 19 ml,
P
= 0.0003) and Qc (Rest: 4.5 ± 1.0 vs 20W: 7.7 ± 1.6 L/min,
P
< 0.0001) increased from rest to 20 Watts, whilst TPR decreased (Rest: 21.3 ± 4.4 vs 20W: 14.0 ± 3.8 mmHg/L/min,
P
< 0.0001); SV reserve was 43 ± 33 %. Aortic diastolic pressure did not change (Rest: 70 ± 12 vs 20W: 76 ± 15 mmHg,
P
= 0.0976), whereas aP1 (Rest: 112 ± 18 vs 20W: 130 ± 20 ml,
P
= 0.0002) and aP2 (Rest: 123 ± 26 vs 20W: 142 ± 25 ml,
P
= 0.0021) increased during exercise (Figure). Notably, aAP was not different between rest and exercise (Rest: 11 ± 11 vs 20W12 ± 11 mmHg,
P
= 0.4969). Therefore, the contribution of aAP to mid-late systolic afterload is unchanged during exercise in HFpEF, unlike in young healthy adults. Unchanged aAP may be a mechanism of high mid-late systolic afterload during exercise in HFpEF, which could contribute to impairments in SV reserve related to reduced ventricular contractile reserve.
Abstract 13672: Quality of Life Impact of Transcatheter Edge to Edge Repair of Mitral Valve With the Mitraclip System in Patients With Mitral Regurgitation and Cardiogenic Shock
Authors: Kerolos Mina M , Chiang Caleb , Eid Joseph , Ritz Ethan , Derbas Laith A , suboc tisha M , Collado Fareed M , Kavinsky Clifford J , Suradi Hussam
Published: June 2023

Introduction:
Transcatheter Edge to Edge Repair (TEER) of the mitral valve is a viable option for patients with moderate to severe mitral regurgitation (MR) who are at high surgical risk. TEER has been shown to improve quality of life (QOL) in patients with MR. Data is limited regarding QOL in patients with MR and cardiogenic shock (CS) who undergo TEER.

Methods:
A single-center, retrospective cohort study including adult patients with moderate to severe MR and CS who underwent TEER between January 2012 and December 2021. CS was defined as a sustained systolic blood pressure <90mmHg for at least 1 hour, use of inotropes, vasopressors, or mechanical circulatory support, and clinical and lab findings of end-organ damage. The primary outcome was change in disease-specific health status (Kansas City Cardiomyopathy Questionnaire-Overall Summary score [KCCQ-OS] at 30 days. Statistical analysis was done using Wilcoxon signed-rank test and t-test.

Results:
Thirty-three patients with mod-severe MR and CS had undergone TEER (See table 1 for baseline characteristics) . KCCQ data were available on 30% survivors at 30 days. KCCQ increased from 17.19 (11.88) before TEER to 53.85 (30.89) in 30 days (mean change 36.67; 95% CI 14.24-59.09; P<0.05, see table2). There was an improvement in 2 out of 4 KCCQ domains; symptoms frequency (mean change 49.17; 95% CI 18.17-80.16; P<0.05) and social limitation (mean change 49.54; 95% CI 22.25-76.83); P<0.05).

Conclusion:
TEER of the mitral valve improves QOL at 30 days in patients with moderate to severe MR and CS.