bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18219: J-Shaped Association Between LDL-Cholesterol Level and Cardiovascular Events: A Longitudinal Follow-Up Study Over 2.4 Million Nationwide Primary Prevention Cohort
Authors: YANG HAN-MO , Park Chan Soon , Han Kyung-Do
Published: December 2023

Introduction:
Low-density lipoprotein (LDL)-cholesterol lowering treatment showed benefits in patients with high atherosclerotic cardiovascular disease (ASCVD) risk.

Hypothesis:
Although high LDL-cholesterol level is known to increase ASCVD risks, prognostic implications of low LDL-cholesterol level remain elusive.

Methods:
Using the data from a Korean Nationwide Cohort, we included 2,432,471 subjects without previous ASCVD. From 2009, subjects were followed for myocardial infarction (MI) and ischemic stroke until 2018. Subjects were stratified according to 10-year ASCVD risks (<5%, 5 to <7.5%, 7.5 to <20%, and ≥20%) and LDL-cholesterol level (<70, 70-99, 100-129, 130-159, 160-189, and ≥190 mg/dL).

Results:
In the overall population (median follow-up: 9.3 years), the relationship between LDL-C level and cardiovascular events showed J-shaped curve. Subjects with LDL-cholesterol <70mg/dL showed increased risk of myocardial infarction compared to those with LDL-cholesterol 70 to <100mg/dL after adjusting covariates in low ASCVD risk group. Similarly, subjects with LDL-cholesterol 70-99 mg/dL and 100-129 mg/dL had lower stroke risks than those with LDL-cholesterol <70mg/dL in low ASCVD risk group. In contrast, LDL-cholesterol level and risks of MI and stroke showed linear association in high ASCVD risk group.

Conclusions:
High LDL-cholesterol level is associated with increased risk of MI or stroke, while low LDL-cholesterol level does not warrant safety from ASCVD in the primary prevention setting.
Abstract 18220: Does Mineralocorticoid Receptor Blockade Affect the Occurrence of Perioperative Atrial Fibrillation in Cardiac Surgery Patients? - A Systematic Review and Meta-Analysis
Authors: Rajak Kripa , Halder Anupam , Ghimire Manoj , Sharma Gautam Seema , Khanal Resha , Jaiswal Vikash , Atrash Anas , Goswami Rohan
Published: December 2023

Background:
Mineralocorticoid receptor antagonists (MRAs) have emerged as potential therapy to prevent atrial fibrillation (AF). However, inconsistent results of MRAs effect on perioperative AF have been reported in the literature in patients undergoing cardiac surgery. To our knowledge, this is the first metanalysis to assess the effect of MRAs on occurrence of perioperative AF in patients undergoing cardiac surgery.

Method:
We searched different electronic databases from inception to April 30th, 2023, for randomized controlled trials (RCTs) and observational studies that evaluated the use of MRAs in patients with heart failure and left ventricular ejection fraction (LVEF) 30-50% who were referred for Coronary Artery Bypass Grafting (CABG) and/or valve surgery without any AF history. Primary outcome was occurrence of perioperative AF. Three independent reviewers selected and appraised the data. A random-effects meta-analysis was performed to estimate pooled odds ratios (OR) and 95% confidence intervals (CI).

Result:
We included 4 studies, 1 RCT and 3 observational cohorts, with a cumulative number of 1,128 patients with mean age 65.15 years. 412(36.5%) received an MRA (spironolactone or eplerenone). The follow up duration was 5 days to 1 month. During follow-up, 118 (28.64%) patients treated with MRAs, developed AF, compared to 224 (31.28%) patients, without MRA treatment. However, metanalysis showed that there is no significant reduction in occurrence of perioperative AF in MRA treated patients (OR: 0.88 CI: 0.58-1.33 p=0.55), I2 53%; Figure]

Conclusion:
Experimental data have shown that MRA blockade prevents perioperative AF in animal models but our metanalysis demonstrated that MRAs were not protective for perioperative AF in patients undergoing cardiac surgery. Larger trials in humans are warranted to evaluate its efficacy, particularly in patients undergoing cardiac surgery.
Abstract 18225: Left Atrial Volume Index and Outcomes in Paroxysmal Atrial Fibrillation (pAF) in the Real-AF Registry
Authors: Minga Iva , Lee Kevin , Lazarus Catherine O , Varley Allyson , Thorne Christopher , Osorio Jose , Singleton Matthew , Zei Paul , DSouza Benjamin , Silverstein Joshua , Metzl Mark
Published: December 2023

Introduction:
Catheter ablation via pulmonary vein isolation Is one of the most commonly performed procedures for treating paroxysmal atrial fibrillation (pAF). Left atrium size affects ablation strategies and outcomes in patients with pAF. We analyzed the left atrium index (LAi) to determine associations with recurrent arrhythmias at 12 months post-ablation and the ablation strategies used.

Methods:
The Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal (pAF) and Persistent (PsAF) Atrial Fibrillation registry (Real-AF) is a multicenter prospective registry that is enrolling patients undergoing AF ablation at high-volume centers. Left atrial volume was reconstructed using CARTO 3D. LAi was separated into normal range: < 34 ml/m2, mildly enlarged 35 - 41 ml/m2, moderately enlarged 42 - 48 ml/m2, and severely enlarged > 49 ml/m2 based on the American Society of Echocardiogram guidelines. Ablation strategies were divided into pulmonary vein isolation (PVI) alone or PVI+ ablation, including PVI and additional atrial arrhythmogenic substrates. Recurrence of arrhythmias at 12 months post-ablation and ablation strategies were compared.

Results:
A total of 1824 were included. In patients with pAF 12.2% developed recurrent arrhythmia at 12 months. When compared to normal LAi, patients with pAF with moderately and severely enlarged LAi were more likely to have a recurrence of arrhythmias at 12 months (Table 1). Women with pAF and moderately and severely enlarged LAi were more likely to have recurrence of arrhythmias (Table 1). A total of 1433 underwent PVI only ablations, and 391 underwent PVI+ ablations. Abnormal LAi was also associated with patients undergoing PVI+ ablations compared to PVI only ablations (Table 1).

Conclusions:
In patients with pAF and abnormal LA size was associated with more recurrent arrhythmias at 12 months post-ablation. Patients with enlarged LAi were more likely to have PVI+ ablations.
Abstract 18229: The Effectiveness of a Student-Delivered Weight Loss Program in a High-Risk Urban Practice
Authors: Cheng Cynthia
Published: December 2023

Introduction:
Obesity is a global epidemic contributing to CVD, the leading cause of death worldwide. Diet, exercise, and lifestyle are crucial to CVD prevention and treatment. The Healthy Eating Index (HEI) is a 13-component dietary analysis tool based on the Dietary Guidelines for Americans, with higher scores associated with lower CVD risk. Calculating the HEI involves a 24-hour food recall and complex scoring. The Diet Risk Score (DRS), a 9-question, efficient alternative screening tool, has been validated against the HEI. JeffWLP, a unique low-cost, long-term student-delivered nutrition education program, evaluates improvement in DRS.

Hypothesis:
JeffWLP participants in JeffWLP would demonstrate significant weight loss, increased physical activity, and improved DRS in urban at-risk patients.

Methods:
In this randomized controlled trial, 30 obese adults from an underserved urban population were randomized to intervention (n=18) or control/usual care (n=12) groups. Mean age was 46 +/- 13 years. 80% were African American, and 90% were female; mean baseline BMI was 38 +/- 5. Mean socioeconomic status, self-assessed using the MacArthur Scale, was 6 (maximum 10). JeffWLP includes 12 core weekly group and individual nutrition education counseling sessions, meal replacements, and an exercise component, followed by unlimited bimonthly maintenance counseling. Vitals were obtained pre, mid, and post-core intervention.

Results:
JeffWLP participants achieved mean weight loss of 6.1 +/- 7.8 lbs (p=0.01), or 2.7 +/- 3.3% body weight (p < 0.01) in 12 weeks. Mean DRS improved by 7 +/- 6 points (p <0.001). Number of weekend steps walked increased by 3500 +/- 3150 (p = 0.016). Pilot JeffWLP patients (n=7), sustained weight loss of 4.8 +/- 8.1 lbs, 285 days after enrollment (p = 0.17).

Conclusions:
Our study demonstrates the cost-effectiveness of JeffWLP for improving weight loss, exercise, and dietary risk in 12 weeks. We anticipate additional sustained improvements in this ongoing study with double the sample size; this additional data will be available at the AHA meeting. JeffWLP empowers medical students to improve health outcomes in disadvantaged, at-risk underserved populations affordably, addressing critical health disparities.
Abstract 18241: Computational Fluid Dynamics (CFD) Exploration of Heart Rate Influence on Wall Shear Stress (WSS) in Coarctation of the Aorta(CoA): Implications for Beta-Blocker Therapy
Authors: Wang Jie
Published: December 2023

Introduction:
CoA's complex hemodynamics may lead to post-repair complications such as pseudoaneurysms. Understanding the effects of beta-blockers, successful in adult heart failure and potentially beneficial for children, is critical. We used a high-resolution image-based CFD model to study these effects on aortic WSS and turbulence in CoA patients.

Hypothesis:
Beta-blocker therapy may favorably influence hemodynamic turbulence stresses.

Methods:
Patient-specific CT scans informed 3D CoA aorta models. Large eddy simulations were conducted at neonatal heart rates of 100, 120, and 160 bpm. Aortic segments were divided into front and back regions based on jet flow impact.

Results:
Despite heart rate-induced turbulence, WSS distributions remained consistent across rates. Lower rates notably decreased maximal systolic WSS distal to the coarctation site but reduced localized WSS and its variability
(6.49 +/- 3.29Pa)
. Both front and back segments showed unique WSS patterns and peak systolic WSS increases with heart rate
(0.1Pa per 10BPM & 0.07Pa/ per 10BPM, P>0.05)
. Significantly higher stress was experienced by the front region
(max: 95.2%, min: 70.4%)
.

Conclusions:
Heart rate changes impact WSS values, indicating heart rate-lowering drugs like beta-blockers may alleviate hemodynamic stress. Despite overall lower WSS, the front region is more susceptible to shear stress at lower rates. This could guide beta-blocker therapy decisions and identify potential beneficiaries.
Abstract 18258: Leucine Supplementation Improves Myocardial Function in a HFpEF Rat Model
Authors: Schauer Antje , Nascimento Alves Paula Ketilly , Augstein Antje , Prieto Jarabo Maria Elisa , Moriscot Anselmo S , Linke Axel , Adams Volker
Published: December 2023

Introduction:
We previously documented that leucine supplementation protects from skeletal muscle atrophy by increasing skeletal muscle mass and force during hind limb immobilization. One of the proposed underlying mechanisms was the suppression of HDAC4 protein expression and increased nuclei accretion.

Hypothesis:
The present study aimed to examine whether the protective effects of leucine supplementation are also observed in the myocardium in an animal model of heart failure with preserved ejection fraction (HFpEF) and to assess the role of HDAC4 modulation.

Methods:
Female ZSF1 lean (control, con) and obese (HFpEF) rats were randomized at an age of 20 weeks to one of three groups: lean rats receiving standard chow (con), obese rats receiving standard chow (HFpEF), and obese rats receiving leucine-supplemented chow (3% w/w) for 12 weeks (HFpEF/leu). All animals underwent echocardiography at baseline and after 6 and 12 weeks. Prior to organ harvest left ventricular (LV) hemodynamics were measured invasively, blood samples were taken, cardiac mitochondrial function was assessed and LV tissue was collected for molecular and histological analyses.

Results:
Assessment of diastolic function revealed a 20% reduction of E/é in the HFpEF/leu group compared to untreated HFpEF. While no alterations of left ventricular hemodynamics were observed between the groups, stiffness factor β was significantly reduced in leucine-treated rats. Left ventricular mRNA levels of Collagen type I a1 and matrix metalloproteinase 2 were reduced by 25% and 22%, respectively. Assessment of mitochondrial oxidative phosphorylation revealed a significant improvement of complex-I- and complex-II mediated respiration in leucine-treated rats compared to HFpEF. Finally, HDAC4 protein expression levels were reduced by 40% in the HFpEF/leu group compared to HFpEF.

Conclusions:
This study presents beneficial effects of leucine supplementation on cardiac function, remodeling, and metabolic parameters in an HFpEF rat model. These benefits may be attributed to suppressed HDAC4 expression.
Abstract 18267: Successful C-Section Delivery at 36 Weeks in a Patient With a Heartmate 3 LVAD
Authors: Soares Cullen , Plazak Michael , Seif Karl , Brophy Ryan , Dees Lynn , Nevin Amanda , Murphy Kristin , BHARADWAJ SHOBANA , Scharf Katelyn T , Sachs Aaron , Forbess Lisa , Liu Stanley , Dahi Siamak , Naselsky Warren , Grazioli Alison , Sankova Susan , Lankford Allison , Ananthram Manjula
Published: December 2023

Introduction:
Pregnancy in patients with advanced heart failure requiring left ventricular assist device (LVAD) support is risky and discouraged, though there are cases of successful deliveries.

Hypothesis:
A 29-year-old G3P2002 female with history of embolic cerebrovascular accident, postpartum hemorrhage, peripartum cardiomyopathy status-post HeartMate 3 (HM3) LVAD, became pregnant after intrauterine device dislodgement. She elected to continue the pregnancy against the advice of maternal-fetal medicine (MFM). A multidisciplinary team convened to plan for delivery.

Methods:
Warfarin and sacubitril-valsartan were stopped due to teratogenicity. Therapeutic anticoagulation with enoxaparin injections was started. Aspirin was continued. Low-dose digoxin was added for right ventricular support. A multidisciplinary team involving anesthesiology, MFM, and advanced heart failure (AHF) was convened. Through patient-centered shared decision-making, cesarean delivery was planned for 36 weeks. She was seen by MFM and AHF every two weeks with LVAD speed optimization under transthoracic echocardiogram (TTE) guidance and anti-Xa monitoring.

Results:
The patient was electively admitted at 35 weeks for pre-delivery optimization. Enoxaparin was switched to an unfractionated heparin infusion. Betamethasone was administered to facilitate fetal lung maturation. Twice-daily fetal non-stimulation tests were performed. LVAD speed was optimized with TTE guidance. Continuous hemodynamic monitoring was performed perioperatively with a Swan-Ganz catheter and arterial line. Femoral veno-arterial sheaths were placed in case extracorporeal membrane oxygenation was needed. Anesthesia was administered via spinal-epidural approach. LVAD speed was modulated as needed. A healthy neonate was delivered by cesarean section without complication at 36 weeks and 3 days.

Conclusions:
Pregnancy during LVAD support remains an extremely high-risk clinical situation, though this case demonstrates that it is possible to carry such a pregnancy to near-term.
Abstract 18306: Race, Natriuretic Peptides, and Physiological Perturbations
Authors: Shetty Naman S , Patel Nirav , Gaonkar Mokshad , Vekariya Nehal , Chu Yuxin , Xie Min , Evitt Niklaus , Musunuru Kiran , Arora Garima , Arora Pankaj
Published: December 2023

Introduction:
Racial differences in natriuretic peptide (NP) levels among young adults are uncharacterized. Race-based differences in NP response to physiological and pharmacological perturbations are unknown.

Methods and Results:
A population-level study in healthy young individuals (18-40 years) with NT-proBNP measurements from the 1999-2004 National Health and Nutrition Examination Survey cycles was conducted. In this study of 3055 individuals, Blacks [34.3% (29.3-38.9%)] had lower NT-proBNP levels compared with Whites. Healthy participants were recruited in 2018-23 in a mechanistic trial to assess the racial differences in NP response to standardized exercise and 6 weeks of metoprolol (started at 50 mg/day and doubled every 2 weeks). MR-proANP was measured pre- and post-exercise, before starting metoprolol and then every 2 weeks till study completion. Among 72 young adults [39 (54.2%) White, 37 (51.4%) females], the increase in MR-proANP levels was higher in Whites [49.0% (38.2-60.6%) compared with Blacks [35.9% (25.2-47.6%)] after exercise (p
int
: 0.004). With metoprolol, MR-proANP levels increased by 36.3% (23.3-50.8%) in Whites and 28.3% (15.0-43.0%) in Blacks (p
int
:0.42). To assess the mechanism of ANP increase, iPSC-CM (3 controls and 3 experiments) were treated with metoprolol to assess the change in NPPA expression. miR-425 (negative regulator of ANP) levels were measured at the abovementioned time points. The expression of NPPA in iPSC-CM did not change on treatment with metoprolol. With metoprolol, the relative expression of miR-425 reduced by ~10% at the end of 6 weeks.

Conclusion:
Using multiple lines of evidence, this study established that healthy young Blacks have lower NP levels and have a blunted NP response to exercise compared with Whites. ANP protein levels differed but no changes in ANP expression were noted with metoprolol. Further work is needed to elucidate pathways underlying miR-425 expression responsiveness with metoprolol.
Abstract 18311: Low and Borderline Ankle Brachial Index Are Associated With Intracranial Aneurysms - A Retrospective Cohort Study
Authors: Laukka Dan , Kangas Essi , Hirvonen Jussi , Rissanen Tiia , Rahi Melissa , Kivelev Juri , Rinne Jaakko , Hakovirta Harri
Published: December 2023

Background:
A low ankle-brachial index (ABI) is associated with a higher risk of cardiovascular diseases, stroke, and systemic inflammation. Intracranial aneurysms (IAs) share similar risk factors with other cardiovascular diseases. However, there is a lack of studies that investigate the association between low ABI and IAs.

Aims:
To study whether low, borderline, or high ABI is associated with an increased risk of IAs compared to a normal ABI.

Methods:
We conducted a retrospective review of all patients (n=2751) who had ABI measurements at our tertiary hospital between 2011 and 2013. Patients with available cerebrovascular imaging or a diagnosis of a ruptured IA were included in the study (n=776) to examine the association between ABI and saccular IAs. The patients were classified into four groups as follows: low ABI (≤0.9, n=464), borderline ABI (0.91-0.99, n=47), high ABI (>1.4, n=56), and normal ABI (1.00-1.40, n=209).

Results:
The prevalence of IAs was 20.3% (18.1% unruptured IAs) in the low ABI group, 14.9% (12.8% unruptured IAs) in the borderline ABI group, 7.0% (5.3% unruptured IAs) in the high ABI group, and 2.4% (1.9% unruptured IAs) in the normal ABI group (p <0.001). In the multinomial regression, which included clinically relevant variables, low ABI (odds ratio [OR], 11.3; 95% confidence interval [CI], 4.1-31.5; p < 0.001) and borderline ABI (OR, 7.1; 95% CI, 1.9-26.6; p <0.001) were the only variables significantly associated with unruptured IAs.

Conclusions:
Patients with low ABI and borderline ABI had a higher prevalence of IAs compared to patients with a normal ABI. The prevalence of IAs was almost 9-fold higher in the low ABI group and nearly 7-fold higher in the borderline ABI group when compared to the normal ABI group.
Abstract 18321: Identifying Predictors of Non-Home Discharge Dispositions Using Machine Learning Among Critically Ill Patients Undergoing Coronary Artery Bypass Grafting
Authors: Bhattacharyya Neel , Zhang Yanjia , Zhang Zhenwei , Ahmed Md Ashfaq , Roy Mukesh , Ramamoorthy Venkataraghavan , Rubens Muni , Saxena Anshul
Published: December 2023

Introduction:
Managing patients undergoing coronary artery bypass graft (CABG) procedures can be challenging. Research shows hospital discharges to locations other than home following CABG are associated with an increased risk of late mortality. We aimed to develop machine learning (ML) models to predict the risk of postoperative discharge dispositions other than home among these patients and assess their long-term postoperative prognosis.

Methods:
The Medical Information Mart for Intensive Care IV database was utilized to identify patients who underwent CABG procedures. The cases were divided into training (75%) and test (25%) sets. The AUROC, accuracy, and F1 scores were used to compare the performance of models. Several methods, such as penalized logistic regression, random forest, SVM, XGBoost, gradient boosting classifier, and lightGBM, were utilized, accounting for variables from demographics, labs, charting events, and comorbidity domains.

Results:
The study included 2228 eligible patients who underwent CABG procedures. The sample consisted of 23% females, 72% whites, and 43% were insured by Medicare. The median age of the sample was 69 years. Among these, 781 (35.05%) patients were discharged to locations other than home. Results show that the gradient boosting method had the highest accuracy (76.8%) with an AUROC of 80.8%. Age, BUN, male sex, PO2, hemoglobin, heart rate, mean arterial BP, chloride, platelet count, and creatinine levels were the top predictors for predicting non-home discharges. Results from the other models represented similar attributes as the top significant predictors.

Conclusion:
Predictors of discharge to locations other than home were identified with high accuracy, and this may aid in selective intervention to reduce the risk of death in this vulnerable patient population. ML can be used to investigate these patterns and possibly highlight particular patient subsets to enhance risk stratification and management.
Abstract 18325: Comparative and Incremental Diagnostic and Prognostic Yield of Exercise ECG, CMR and SPECT in Patients With Suspected Ischaemic Heart Disease: A CE-MARC Sub-Study
Authors: Bisaccia Giandomenico , Swoboda Peter P , Bucciarelli-Ducci Chiara , Plein Sven , GREENWOOD John
Published: December 2023

Background:
Guidelines recommend exercise ECG and stress imaging as first line diagnostic tests for the management of patients with suspected ischemic heart disease (IHD). We compared 1) the accuracy in detection of angiographically defined IHD and 2) the prognostic significance of exercise ECG, single photon emission computed tomography (SPECT) and cardiovascular magnetic resonance (CMR), as well as the sequential use of exercise ECG and an imaging test, in the CE-MARC study.

Methods and Results:
Of 752 patients in CE-MARC, 580 had exercise ECG and angiography, and 503 also had SPECT and CMR. The sensitivity, specificity, positive and negative predictive values (95%CI) of exercise ECG were 68.3 (61.9,74.0), 72.5 (67.6,76.9), 61.0 (54.8,66.8), 78.4 (73.7,82.5). Exercise ECG was significantly less sensitive than CMR and less specific than CMR and SPECT. Furthermore a positive exercise ECG result was not predictive of MACE at follow-up (HR 1.14 [95% CI 0.75 to 1.72], p = 0.53). Sequential SPECT following an inconclusive exercise ECG compared to SPECT alone resulted in improved sensitivity (86.3% vs. 65.5%) and negative predictive value (79.0% vs. 87.9%) but at a cost of reduced specificity and positive predictive values (83.7% vs. 64.1%; 72.1% vs. 60.7%), and was not prognostically significant (HR 2.31 [95% CI, 0.88 to 6.08], p = 0.091). CMR alone had greater diagnostic and prognostic yield than exercise ECG, SPECT or a combination of the two. Sequential CMR in patients with inconclusive exercise ECG did not outperform CMR alone, but allowed effective prognostication (p = 0.011), contrary to SPECT (p = 0.081).

Conclusions:
In patients recruited to CE-MARC, exercise ECG was less sensitive than CMR and less specific than both CMR and SPECT. Positive exercise ECG results had no clear prognostic value. CMR alone was more sensitive and offered greater prognostic yield than exercise ECG, SPECT, or a combination of both. Diagnostic and prognostic yield of CMR was not improved by combination with exercise ECG. Importantly, sequential use of CMR, but not SPECT, improved prognostication following an inconclusive exercise ECG.
Abstract 18336: Accuracy of Antiarrhythmic Drug Dosing Using a Computer-Guided Decision Tree Model
Authors: Navara Rachita , Ravuri Riya , Devgun Jasneet , KUMAR RAJ , Ozkan Ecem , Paudel Bishow M , Lucy Daniel , Ananth Esha , Sujay Sheth , Dopierala Maria , Chen Devon , Pallod Aditi , Kheiri Babikir , Malcolm Katherine , Venkateswaran Ramkumar , Martinez Alejandro Alvarez , DeLeon Rania , Higgins John , Patel Kunj G
Published: December 2023

Background:
Atrial fibrillation (AF) is the most common heart rhythm disorder and often requires inpatient monitoring for antiarrhythmic drug (AAD) initiation, specifically for dofetilide and sotalol. No system currently offers safe at-home AAD initiation, which is needed to expand AAD access for low-risk or underserved patients and reduce mortality.

Objective:
Assess accuracy of AAD dosing using a computer-guided decision tree algorithm compared to physician dosing decisions.

Methods:
Patients in an all-comer population were instructed to take a mobile ECG (mECG; KardiaMobile 6L, AliveCor). A proprietary ML algorithm (SafeBeat Rx) interpreted QTc for each mECG and recommended a starting dose for each AAD (dofetilide and sotalol), per drug labeling. For sotalol, an initial dose of 80 mg was recommended if QTc ≤ 450 ms and HR > 60 bpm; if baseline ECG criteria were unmet, 0 mg was recommended. For dofetilide, initial 500 mcg dose was recommended if QTc ≤ 440 ms. For software simulation, creatinine clearance was assumed to be normal (>60 mL/min) for all patients. Recommendations were adjusted based on a higher QTc threshold >550 ms if the patient’s baseline ECG showed wide QRS (e.g. artificially paced, bundle branch block). The software recommendations were compared to the gold standard: dosing selected by 2 physicians manually measuring baseline mECG QTc and selecting a theoretical starting dose accordingly, independent from software-generated results.

Results:
95 patients were enrolled (40% healthy, 30% outpatients, 30% inpatients). The algorithm was highly accurate in predicting starting dose; agreement with physicians was 94.68% for sotalol and 95.74% for dofetilide. Median heart rate was 84.8 bpm (SD = 17.5) and median QTc interval was 475.5 ms (SD = 106.4). Physicians chose the manufacturer-recommended full starting dose for 85% of patients for sotalol and 86% for dofetilide, compared with 86% for sotalol and 86% for dofetilide recommended by the software.

Conclusion:
The decision tree model had 95% agreement with physician dose recommendations, demonstrating that the algorithm can accurately guide patient-specific AAD dosing, which helps guide remote physician-directed initiation of AAD, ultimately expanding drug access for AF patients.
Abstract 18358: Preclinical Evaluation of the Safety and Activity of JK07, A Novel Bifunctional Neuregulin Antibody Fusion Which Selectively Activates ErbB4, for the Treatment of Heart Failure
Authors: Murphy Samuel L , Tang Wai Hong W , Zhuang Xiaolei , Li John
Published: December 2023

Background:
Neuregulin (NRG) is a cardioregenerative growth factor that stimulates ErbB3 and ErbB4 signaling. NRG exhibited promising activity clinically in NYHA II/III heart failure (HF) patients, but concerns over cancer risk and GI tolerability limited development. Selective ErbB4 agonism might improve the tolerability and safety of NRG, but this hypothesis has not been evaluated previously due to lack of a selective ErbB4 agonist. JK07 is an ErbB3 antagonist antibody fused with the active domain of NRG-1, designed to selectively stimulate ErbB4.

Methods:
ErbB3 and ErbB4 activation by JK07 was evaluated in vitro in comparison to NRG-1. A left anterior descending (LAD) ligation model of HF in rats evaluated the ability of JK07 to improve left ventricular ejection fraction (LVEF) and alleviate symptoms of HF in comparison to control antibody-fused NRG-1. A rhesus macaque model of spontaneous heart failure was used to evaluate JK07’s ability to improve LVEF in animals with reduced LVEF (HFrEF) and to improve diastolic dysfunction in animals with preserved LVEF (HFpEF), in comparison to vehicle control and sacubitril/valsartan.

Results:
JK07 showed ErbB4 activation equivalent to NRG-1 in vitro, but significant attenuation of ErbB3 activation. In the LAD ligation model, JK07 induced dose-dependent increased LVEF, reverse remodeling, reduced collagen I deposition, reduced peripheral edema, increased exercise capacity and decreased infarct size. JK07 improvements were comparable to control NRG. In the rhesus model of HFrEF, both sacubitril/valsartan and JK07 treatment increased EF by at least 5% absolute in 7/10 animals, compared to 0/6 animals with placebo. In the rhesus model of HFpEF, diastolic dysfunction was improved by at least one grade in 6/10 animals receiving JK07, 1/10 animals receiving sacubitril/valsartan, and 0/6 animals receiving placebo.

Conclusions:
JK07 selectively activates ErbB4 in vitro. In a rodent LAD model of HF, selective ErbB4 activation was as effective as NRG-1 in improving LVEF and symptoms. In a spontaneous heart failure model in rhesus macaques, JK07 treatment was comparable to sacubitril/valsartan in the treatment of HFrEF and superior to sacubitril/valsartan in the treatment of HFpEF.
Abstract 18381: Long-Term Coronary Artery Disease Risk in Female Adults With
Surgically-Induced Menopause
: A Systematic Review
Authors: Kearn Natalie , Mensour Emma A , Liblik Kiera , Sirwani Barkha , Gulati Martha , Ahimsadasan Nilah , Johri Amer
Published: December 2023

Introduction:
Coronary artery disease (CAD) is a leading cause of morbidity and mortality in female adults. Prior studies have suggested an association between surgically-induced menopause (SIM) and long-term CAD risk. Yet, the pathophysiology and clinical significance of this relationship remains unclear. As SIM causes a premature cessation of potentially cardioprotective hormones, this review aimed to further investigate if SIM is a risk factor for CAD.

Methods:
SCOPUS, Web of Science, Cochrane Library, OVID/Embase, SciELO, and LILACS were searched from inception to April 2023 for observational studies reporting the effects of hysterectomy, oophorectomy, and/or salpingectomy prior to age fifty on long-term CAD risk.

Results:
Among 3056 identified records, nineteen studies were included with a combination of benign and malignant surgical indications. The studies reported on coronary heart disease (n=6), CAD (n=4), ischemic heart disease (n=3), and myocardial infarction (n=7). Sixteen articles with an average of 106,433 participants per study demonstrated a significantly increased risk of CAD following SIM (Table 1). In particular, hysterectomy with or without bilateral oophorectomy, and bilateral oophorectomy alone were found to have the most profound influence. Unilateral oophorectomy or hysterectomy with salpingo-oophorectomy did not appear to increase CAD risk. Average follow-up duration after SIM ranged from six to twenty-four years. Five studies adjusted for post-menopausal hormone replacement therapy use.

Conclusions:
SIM may elevate long-term CAD risk following hysterectomy and/or bilateral oophorectomy. Given that the majority of SIM are performed pre- or peri-menopausal for benign indications, understanding the associated cardiovascular risks is vital for informed decision-making, early detection, and prevention.
Abstract 18388: Hypertension Identification and Management in the USA: Adherence of the 2017 ACC/AHA High Blood Pressure Guidelines
Authors: Heaton Joseph , Alshami Abbas , Udongwo Ndausung , Dandu Sowmya , Mararenko Anton , Imburgio Steven , Akhlaq Hira , Johal Anmol , Almendral Jesus , Sealove Brett
Published: December 2023

Background:
The 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults changed the criteria for a diagnosis of hypertension and provided new recommendations goals and management. We aimed to investigate the prevalence of hypertension identification, treatment, and adherence in the US population.

Methods:
We analyzed the 2017-2020 pre-pandemic National Health and Nutrition Examination Survey for participants between 18 and 79 years of age. Participant data was used to assess for a hypertension diagnosis and eligibility for AHA/ACC’s primary or secondary prevention hypertension strategies. Current hypertension medication usage was stratified if prescribed for hypertension management or a non-hypertension indication. Participants with a current hypertension-indicated medication were identified as “Undergoing Treatment”; all other participants were stratified into “No Indication”, “Primary Prevention”, or “Secondary Prevention”, based on the AHA/ACC guideline. Complex survey methodology with weighting was utilized for national estimates.

Results:
Our study included 236,621,712 participants, of which 22.4% (n=53,064,773) were undergoing treatment for hypertension, 67.0% (n=158,613,605) had no indication for management, 8.9% (n=21,158,544) qualified for primary prevention, and 1.6% (n=3,784,790) qualified for secondary prevention. A known hypertension diagnosis was reported in 26.0% of the primary prevention group, 45.0% of secondary prevention, and 94.8% of those undergoing treatment. In patients undergoing treatment, 57.9% of participants had mean blood pressure readings above goal.

Conclusion:
One in ten adults under 80 qualify for hypertension management but may not be undergoing treatment. Of patients qualifying without current treatment, most did not know they would qualify for a hypertension diagnosis. More than half of treated patients did not meet blood pressure goals.
Abstract 18426: Secreted Frizzled-Related Protein 1 Mediates Adipogenic Differentiation of Vascular Cell Adhesion Protein 1 Fibroadipogenic Progenitors in the Ischemic Limb
Authors: Dai Qunsheng , Wan Changxin , Fei Kaileen , Xu Yueyuan , Peters Derek , Garrett Brianna , Otto James , Kontos Christopher D , Ji Zhicheng , Diao Yarui , Southerland Kevin W
Published: December 2023

Introduction:
Chronic limb threatening ischemia (CLTI) patients display a skeletal muscle myopathy that is hallmarked by fatty infiltration. The replacement of functional muscle fibers with adipocytes impairs ambulatory function and is associated with poor clinical outcomes. The cell type responsible for fatty infiltration is a mesenchymal stromal cellular population, term fibroadipogenic progenitors (FAPs). We previously demonstrated that Vcam1+ FAPs represent a sub-population with increased adipogenic potential. However, the molecular mechanisms which govern Vcam1+ FAP mediated adipogenesis remain unknown. Herein, we sought to identify the intracellular mechanisms that drive Vcam1+ FAPs into an adipogenic cellular fate.

Methods:
We used single cell and bulk RNA-sequencing to identify Sfrp1 as an enriched gene in Vcam1+ FAPs. Next, to determine the sufficiency and necessity of Sfrp1, we overexpress Sfrp1 with a recombinant protein and inhibit Sfrp1 with a siRNA and assess adipogenesis. To assess the clinical significance of this FAP subpopulation, we apply single-cell RNA sequencing to CLTI patients.

Results:
We show in a CLTI murine model that Vcam1+ FAPs are enriched in Sfrp1. Next, we demonstrate that Sfrp1 is both sufficient and necessary for the differentiation of Vcam1+ FAPs into adipocytes. Finally, we demonstrate that human CLTI patients also have a pathologic FAP population that is enriched in Vcam1 and Sfrp1Conclusions: Our results reveal a novel mechanism for fatty infiltration, a histologic hallmark of CLTI patients, in the ischemic limb. We also validate the clinical significance of Vcam1+ Sfrp1+ FAPs by demonstrating the presence of this population in human CLTI patients. This work lays the foundation for future studies aimed at inhibiting fatty infiltration and promoting skeletal muscle regeneration in CLTI patients.
Abstract 18443: Early Inflammation in βII-Spectrin Deficient Hearts Promote Cardiac Remodeling and Heart Failure
Authors: Scott Shane S , Matzko Anna , Greenlee Ashley , Schwendeman Ethan , Smith Sakima A
Published: December 2023

Background:
Dysregulation of cardiac cytoskeletal proteins such as βII-spectrin has been recognized to promote accelerated heart failure (HF) and arrhythmias in human and mouse models. However, the mechanism by which βII-spectrin dysregulation underlies HF is poorly understood.

Hypothesis:
We hypothesized that cardiomyocyte loss of βII-spectrin leads to recruitment of inflammatory macrophages that augment cardiac remodeling by promoting arrhythmogenesis and increased susceptibility to HF.

Methods:
Cardiomyocyte-specific βII-spectrin knockout (βII-cKO) and control mice (βII-flox) were generated and harvested for RNA-sequencing (RNA-seq), qRT-PCR (to validate candidate inflammatory genes), immunohistochemistry, immunoblotting, and flow cytometry. siRNA was also used to knockdown βII-spectrin in cultured cells to validate that direct loss of βII-spectrin contributes to immune cell recruitment. Transaortic constriction (TAC) was used to induce pressure overload.

Results:
RNA-seq demonstrated an early significant increase of inflammatory macrophages and T cell markers following βII-spectrin loss. Consistent with RNA-seq and qRT-PCR results, immunohistochemistry demonstrated an increase in CD45 positive cells in juvenile βII-cKO mouse hearts compared to control. siRNA targeted depletion of βII-spectrin in cultured cardiomyocyte led to increased expression and secretion of TGFβ-1 protein, which can promote infiltrating of immune cells. Notably, accelerated HF at two weeks was observed in βII-cKO mice compared to controls after TAC.

Conclusions:
These data suggest that βII-spectrin loss may mediate inflammation via the TGFβ-1 pathway, which in part contributes to βII-spectrin-mediated accelerated HF. Furthermore, these are the first data implicating βII-spectrin in the TGFβ1-immune signaling pathway in cardiomyocytes.
Abstract 18470: The Impact of Cardiovascular Health Intervention on Plasma Metabolomic Profiles: Results From the Morehouse-Emory Cardiovascular Center for Health Equity
Authors: Beydoun Nour , Vasta Nishant , Liu Chang , Rooney Kimberly , Sun Yan , Pemu Priscilla , Taylor Herman A , Jones Dean , Quyyumi Arshed A , Searles Charles D
Published: December 2023

Introduction:
Previously, we used plasma metabolomics profiling to identify metabolites underlying cardiovascular health (CVH) in participants of the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity study, a cohort of Black adults living in the greater Atlanta metropolitan area. To determine whether a health intervention could alter expression of metabolites associated with CVH, metabolomics profiles were assessed pre- and post-intervention in participants with poor CVH.
Hypothesis:
Metabolites previously shown to be associated with CVH in MECA participants would be altered after the health intervention.

Methods:
Seventy-one Black adults without known cardiovascular disease and with poor CVH (AHA Life’s Simple 7 [LS7] score <8), used a technology-enabled behavioral intervention platform for 6 months with or without a health coach. Metabolomics profiles were assessed pre- and post-intervention by high-resolution metabolomics profiling. A metabolome wide association study (MWAS) identified differentially expressed metabolites and enriched metabolic pathways. Metabolites were annotated by matching to an in-house library of confirmed metabolites. Changes in clinical metrics after intervention were also explored.

Results:
Mean age was 55 (standard deviation [SD] 9.0) years, 69% female. Total LS7 scores improved from 6.2 (SD 1.49) to 6.5 (SD 1.74) after the intervention. While total and subcomponent LS7 scores and clinical metrics (BMI, blood pressure, glucose and cholesterol levels) trended toward improvement, the changes were not statistically significant. MWAS identified 18 confirmed metabolites that were significantly changed after intervention, including glutamine and glutamate. Pathway analysis identified 29 enriched metabolic pathways, including those for glutamate, aspartate, asparagine, arginine and proline metabolism.

Conclusions:
A six-month lifestyle intervention significantly altered activity of select plasm metabolites while only modestly altering clinical metrics. These metabolites appear to be sensitive indicators of a healthier lifestyle, potentially supporting their use as markers of CVH and therapeutic targets.
Abstract 18473: Role of Linguistic Acculturation and Physical Activity With Risk of 1 Year Hospital Readmission After Suspected Acute Coronary Syndrome
Authors: Romero Emily K , Xu Chang , Sanchez Gabriel J , Murdock Margaret E , Cruz Gaspar J , Jurado Ammie , Duran Andrea T , Boudreaux Benjamin D , Edmondson Donald E , Diaz Keith M
Published: December 2023

Background:
Disparities in acute coronary syndrome (ACS) outcomes after hospital care exist beyond racial and ethnic factors. In particular, low linguistic acculturation (LA) may impact care and lead to poorer prognosis. Few studies have examined LA’s impact on outcome disparities post-hospitalization and identified modifiable behaviors, such as physical activity (PA) engagement, that can mitigate risk.

Aim:
To evaluate the association of LA with 1-year hospital readmission risk among patients evaluated for ACS and examine PA as an effect modifier.

Methods:
Patients evaluated for ACS in the emergency unit (n=609, 47.8% female, 58.0% Hispanic, 63±12yrs) were studied. LA was classified into three levels (low, intermediate, high) based on patient’s self-reported native and preferred languages and English fluency. Continuous total PA was objectively assessed 30 days post-discharge via a GENEActiv accelerometer worn on the non-dominant wrist. One-year all-cause hospital readmissions were ascertained via hospital medical record searches. Cox regression models used high LA as referent group.

Results:
Over 1-year follow-up, 264 (44.0%) patients had a subsequent hospital admission. Low LA was associated with increased 1-year readmission risk after adjusting for demographic factors, comorbidities, disease severity, and PA indicators (intermediate HR=1.44; 95% CI: 0.91-2.28; low HR=1.63; 95% CI: 1.05-2.55; p-trend=0.035). PA moderated this association (p-interaction=0.003). Low LA was only associated with greater risk of 1-year readmission among those with low PA levels (below median of 158 min/day; HR=1.88; 95% CI: 1.00, 2.79). Among those with high PA, the association between low LA and risk of readmission was attenuated and not statistically significant (HR=1.46; 95% CI: 0.75, 2.83).

Conclusion:
Among a diverse cohort of patients with suspected ACS, LA was associated with reduced risk of 1-year hospital readmission. PA significantly moderated this relationship, with higher volumes of PA attenuating the positive association between low LA and increased risk of 1-year hospital readmission. These findings implicate low LA as a potential risk factor for readmission post-ACS and suggest increased engagement in PA can help mitigate this risk.
Abstract 18481: Paroxysmal Atrial Fibrillation and Sleep Apnea: Diurnal Patterning of Autonomic Function and Influence of CPAP Therapy
Authors: Khazaie Sepideh , Wang Lu , farhad kaffashi , Sandhu Ahana , Chung Mina K , Heinzinger Catherine M , Van Wagoner David R , Loparo Kenneth , Mehra Reena
Published: December 2023

Introduction:
Autonomic nervous system (ANS) dysfunction is implicated in sleep-disordered breathing (SDB) and atrial fibrillation (AF).

Hypothesis:
We hypothesize that ANS measures of heart rate variability (HRV) exhibit diurnal differences in paroxysmal AF(PAF) relative to SDB severity and is impacted by continuous positive airway pressure (CPAP).

Methods:
Data from the Sleep Apnea and Atrial Fibrillation Biomarkers and Electrophysiologic Atrial Triggers (SAFEBEAT) study including PAF (7-24 day ECG monitoring), concomitant actigraphy and SDB from polysomnography at baseline and 3-months post-CPAP were analyzed. Linear mixed-effects models were used to assess SDB (apnea hypopnea index (AHI), hypoxia (%sleep time with SaO2<90% and nadir SaO2) and diurnal average HRV (frequency domain (sympathovagal)): low-frequency range (LF), high-frequency range (HF), LF/HF; time domain: mean of normal RR interval (MNN), standard deviation of NN intervals (SDNN), SD1(Poincare plot standard deviation) and effect of 3-month CPAP.

Results:
In 44869 five-minute epochs from 109 participants with SDB and PAF, during wakefulness, associations of AHI and LFP, nadir SaO2 with sympathovagal measures (LFP, LHR) and time domain measures (SDNN, SD2) were observed. A sleep-wake significant interaction was observed with all HRV measures and stronger associations in wake than sleep. Baseline to follow-up CPAP time domain measures were increased during wakefulness (MNN, SDNN, RMSSD, CV, SD1, and SD2) and increased during sleep (MNN, SD2, LHR).

Conclusions:
Diurnal variation of autonomic measures in moderate to severe SDB was observed and association with SDB severity was more pronounced during wakefulness; CPAP influenced autonomic function. These findings in earlier onset AF may contribute to electrophysiological remodeling with implications for ANS-specific chronobiology in SDB.
Abstract 18489: Double Edged Sword: SGLT-2 Inhibitors in the Immunosuppressed Heart Failure Patient
Authors: Brown Christina , Addis Jessica , Mohamed Fazad
Published: December 2023

Introduction:
SGLT-2 inhibitors are often prescribed for patients with heart failure, as a part of Goal Directed Medical Therapy. There is a known risk of genitourinary tract infections with utilizing this medication class. We present a case of a patient on chronic immunosuppression therapy on Dapagliflozin who developed a prostate abscess.

Case Description:
70-year-old male with history of cardiac sarcoidosis on prednisone and mycophenolate mofetil, non-ischemic cardiomyopathy, and atrial fibrillation who initially presented with suprapubic pain and urinary urgency for two weeks. Urinalysis was positive for glucose greater than 1,000 and urine culture positive for Klebsiella pneumoniae. CT imaging revealed a prostate abscess measuring 4.5 x 4.4 x 5.7cm. Patient underwent CT guided drainage of the prostate abscess with thick, purulent drainage that cultured positive for Klebsiella pneumonia. He was initially started on an 8-day course of Ceftriaxone but transitioned to Trimethoprim-Sulfamethoxazole for 6-weeks at discharge. He was previously prescribed Empagliflozin for heart failure, however, this was discontinued due to expense and was switched to Dapagliflozin four months prior to presentation.

Discussion:
SGLT-2 inhibitors are commonly prescribed in heart failure patients. We encourage special consideration in patients at increased risk of infection, prior to starting SGLT-2 inhibitors as they may have more complicated manifestations of side effects. In this case, the patient underwent procedural interventions and required long term antibiotic therapy as a consequence of SGLT-2 inhibitor use.

Conclusion:
Patients who are chronically immunosuppressed are at increased risk for infections, including genitourinary, compared to the general population. While trying to optimize patient's cardiomyopathy, it is imperative to consider their risk for developing complications when initiating SGLT-2 inhibitors in immunocompromised patients.