bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14374: The Atrium Conduction Mappings Using Omnipolar Technology for Detecting Epicardial Connection in Patients With Atrial Fibrillation
Authors: Kogame Takehiro , Mine Takanao , Fukuhara Eiji , Sugitani Miho , Ishihara Masaharu
Published: December 2023

Background:
Epicardial connection (Epi-connection) between the right atrium (RA) and right pulmonary vein (RPV) has been known to complicate pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Meanwhile, the omnipolar voltage detected using EnSite™ Omnipolar Technology (OT) has been reported to facilitate the recognition of wavefront direction and see every signal in 360 degrees.

Purpose:
We investigated whether epicardial RA-RPV connection can be evaluated with OT mapping before PVI.

Methods:
We prospectively studied 113 consecutive patients (74 males, age 71±10 years, 68 paroxysmal AF) who underwent initial pulmonary vein isolation (PVI) for AF. The RA-RPV connections before PVI were assessed using OT mappings during right atrial pacing. True Epi-connections were defined as cases that required additional ablation medial to the PV more than 1 cm from the ablation line after the right PVI.

Results:
RA-RPV connections before PVI were detected in 7 out of 113 patients (6.2%). True Epi-connections were confirmed in 7 out of 113 patients (6.2%, 6 patients with carina and 1 with right superior PV) and were not related to any other clinical data, blood samples, or echocardiographic findings. Only 5 out of 7 patients with RA-RPV connections before PVI showed True Epi-connections (Figure).

Conclusion:
The prevalence of Epi-connections is not high, however, the conduction mapping using OT could be useful for detecting Epi-connection (especially non-carina Epi-connection) before PVI.
Abstract 14390: Interatrial Block in the Presence of Lipomatous Hypertrophy of the Interatrial Septum
Authors: Malik Abdulaziz , John Kevin , Wahoud Mohamad , Humos Basel , Rozen Guy , Chee Jennifer , Homoud Munther , Madias Christopher
Published: December 2023

Introduction:
Interatrial block (IAB) from disruption of conduction through Bachmann’s bundle results in atrial electromechanical dysfunction. Delay in conduction and alteration in the pattern of atrial activation causes P-wave lengthening (≥120 ms) and characteristic biphasic P-waves in the inferior ECG leads. IAB has been associated with atrial arrhythmia and risk of stroke. Generally, the anatomic substrate for IAB is a fibrotic atrial myopathy; however, intertrial masses have also been associated with IAB. Lipomatous hypertrophy of the interatrial septum (LHIS) constitutes an anatomical barrier that could similarly lead to IAB.

Hypothesis:
The presence of LHIS is associated with an increased prevalence of IAB.

Methods:
A query of the echocardiography database at our institution from 2017 to present revealed 312 subjects with LHIS. Data collection included demographic characteristics, ECG and echocardiographic parameters. Prevalence of IAB and associated clinical variables were assessed.

Results:
The mean age was 72 years (56% male). In the total group IAB was present in 131 patients (42%). Comparison between the group with IAB versus without IAB was notable for a higher prevalence of stroke in those with IAB (24 subjects versus 16; p value = 0.013). The prevalence of atrial fibrillation was not statistically different between the two groups, but atrial flutter was noted to be more prevalent in those with IAB (16 subjects vs 9; p value = 0.018). Hypertension and male sex were also associated with IAB.

Conclusions:
Subjects with LHIS have a high prevalence of IAB, likely consequent to localized disruption in conduction through Bachmann’s bundle. We demonstrate a higher prevalence of atrial flutter and stroke in those with LHIS and IAB. These results highlight the importance of LHIS as a potential cause of IAB that can contribute to atrial structural remodeling and electromechanical dysfunction associated with atrial arrhythmia and stroke.
Abstract 14407: Right Ventricular Myocardial Stiffening is Associated With Pulmonary Arterial Stiffening in Pulmonary Hypertension
Authors: Neelakantan Sunder , MANNING EDWARD P , Zhang Peng , Choudhary Gaurav , Avazmohammadi Reza
Published: December 2023

Introduction:
Pulmonary hypertension (PH) increases vascular resistance in the lung leading to remodeling of the proximal pulmonary artery (PA). PH also leads to the right ventricular (RV) remodeling following increased RV afterload. Studies of tissue remodeling in PH have focused on either the RV or PA, leaving the understanding of the RV-PA remodeling relationship elusive. We hypothesize that PA proximal tissue stiffening is associated with RV free wall (RVFW) stiffening.

Methods:
The mild model of PH was developed by placing SD rats (n=6) in a hypoxia chamber (10% O2) for 3 weeks, followed by one week of normoxia. The severe model of PH was developed by injecting one dose of SU5416 (20 mg/kg sc) into CDF rats (n=6) followed by the hypoxia protocol. Control rats (n=6 each for SD and CDF) were kept in normoxia at all times. Each group was half male and half female. RVFW and main PA tissues were harvested and characterized through mechanical tests. Tissue stiffness was calculated as the slope of the ensemble stress-strain curve (sum of circumferential and longitudinal stress) at a large strain (>30%) for the RVFW and PA specimens.

Results:
RVSP increased, and PAT decreased in both models. These changes were significant only in the severe model (Figs. 1A, B). Similarly, RVFW and PA stiffnesses increased significantly only in the severe model (Figs. 1C, D). A significant positive correlation between RVFW and PA stiffness was observed (R2 = 0.59, p=0.0001, Fig. 1E).

Conclusions.
Our results demonstrate, for the first time, a significant correlation between RVFW and PA stiffening in PH. Proximal PA stiffening changes the pulsatile component of the RV afterload, contributing to the RVFW stiffening, which is known to be a key precursor of RV failure. Our results suggest that the proximal PA stiffening may worsen RV stiffening independent of increases in PA distal resistance. Further studies are needed to determine the role of resistive vs. pulsatile RV afterload in the outcome of RV remodeling.
Abstract 14411: Block in the Fasciculoventricular Pathway in a Complex Arrhythmia Presentation
Authors: Suppah Mustafa , Iyengar Shruti K , Srivathsan Komandoor S
Published: December 2023

Background:
Fasciculoventricular pathway (FVP) is a rare form of preexcitation without known clinical tachycardia. As it is connected to the His bundle, they conduct whenever it is engaged. Conduction through the His Bundle but block at FVP has not been reported.

Case presentation:
We present a case of a 42-year-old male with a history of Wolff-Parkinson-White syndrome (WPWS), supraventricular tachycardia (SVT), syncope, embolic stroke, paroxysmal atrial fibrillation, hypertension, hypothyroidism, Sjogren's syndrome and prior unsuccessful attempts at elimination of the preexcitation. He underwent electrophysiology (EP) study for presumed SVT ablation. The EP study identified an FVP as the cause of preexcitation, and the planned accessory pathway ablation was deemed unnecessary. Atrial tachycardia originating from the right superior pulmonary vein (PV) was induced, eventually degenerating into atrial fibrillation, and the patient successfully underwent pulmonary vein isolation with the resolution of symptoms.

Discussion:
FVP is usually an incidental finding when patients with symptomatic preexcitation are studied. If tachycardia is induced, it is unrelated to the preexcitation. The FVP is connected to the His bundle and invariably conducts if the impulse engages the His Bundle. We are unaware of a case when the His bundle conducts, but the impulse loses preexcitation due to a block in the FVP. This unusual finding was noted in our case. To further confirm the location of the accessory pathway, IV adenosine was given with a complete heart block suggesting the preexcitation is beyond the level of the AV node and within the conduction system. It is not at the annulus with independent atrial and ventricular insertion, typical of an accessory pathway.

Conclusions:
This case demonstrates an FV pathway's unusual conduction block and physiological characteristics.
Abstract 14413: Contemporary Prevalence, Comorbidity Burden, and Treatment of Overweight and Obesity: Insights From the Multicenter Mass General Brigham Healthcare System
Authors: Ostrominski John W , Smith Austen M , Unlu Ozan , Zelle David J , Baer Heather , Tucci Michela , Fabricatore Anthony , O Hartaigh Briain , Toliver Joshua , Michalak Wojciech , Olsson Kelly , Cannon Christopher P , Apovian Caroline , Scirica Benjamin , Blood Alexander J
Published: December 2023

Background:
Real-world evidence is critical to identify treatment gaps and inform healthcare service design, but contemporary anti-obesity medication (AOM) use patterns are sparsely reported.

Aims:
To describe the prevalence of obesity/overweight, evidence-based obesity-related conditions (ORCs), and AOM use among eligible patients, with a focus on cardiovascular disease (CVD).

Methods:
In this cross-sectional analysis of the multicenter Mass General Brigham healthcare system spanning 2018-2022, we identified all adult patients eligible for AOM (BMI 27-29.9 kg/m
2
with ≥1 ORC or BMI ≥30 kg/m
2
). The prevalence of ORCs was ascertained using administrative codes and available EHR data. Prescription of FDA-approved AOM by BMI category, number of ORCs, number of key CVD risk factors, and the presence of prior MACE were also evaluated.

Results:
Of 2,469,473 individuals who met inclusion criteria, 1,111,396 (44%) were eligible for AOM (mean age, 54 years; 57% female). Of these, 31%, 41%, 17%, and 11% had a BMI (kg/m
2
) of 27-29.9, 30-34.9, 35-39.9, and ≥40, respectively. Prior metabolic/bariatric surgery was seen in 1%. Musculoskeletal disorders (54%), dyslipidemia/hyperlipidemia (36%), and hypertension (35%) were the most common ORCs, with ≥2 ORCs observed in 62%. Prescription of any FDA-approved AOM was observed in only 1.4% of all eligible patients. Liraglutide 3.0 mg (46% of all AOM) was the most prescribed AOM. AOM prescriptions increased modestly with higher BMI, ORC burden, and number of CVD risk factors (
Figure
). Among those with prior MACE (9%), 1.2% (1.0% if without T2DM) were prescribed FDA-approved AOM.

Conclusions:
Although more than 1 in 3 contemporary patients in a large healthcare system are eligible by guidelines and FDA labeling, AOM prescription remains exceedingly low, even among high-risk persons with severe obesity and established CVD. Novel care delivery pathways are needed to accelerate closure of these considerable implementation gaps.
Abstract 14420: Role of Thromboprophylaxis in Outpatients With COVID-19: A Meta-Analysis of Randomized Controlled Trials
Authors: Singh Sahib , Tantry Udaya , Bliden Kevin , Garg Aakash , Gurbel Paul
Published: December 2023

Introduction:
COVID-19 has been known to cause a hypercoagulable state, leading to venous and arterial thromboembolism. While thromboprophylaxis with anticoagulation (AC) agents is beneficial in hospitalized patients, their role is unclear in outpatients with COVID-19. We conducted a meta-analysis to assess the potential role of AC in outpatients with COVID-19.

Methods:
Multiple online databases were searched for randomized clinical trials (RCTs) comparing prophylactic AC to placebo in patients presenting in the outpatient setting with COVID-19. The primary outcomes of interest were hospitalization, death, venous thromboembolism (VTE) and bleeding at the longest available follow up. A random-effects model was used to estimate pooled risk ratios (RR) and 95% confidence intervals (CI).

Results:
Four RCTs with a total of 1,464 patients (AC group n=726, placebo group n=738) were included. The mean age was 55 years, 48% of patients were men and the mean duration of follow up was 65 days. Both groups had similar risk of hospitalization (RR 0.93, 95% CI 0.56-1.53, p = 0.76) (Figure 1), death (RR 1.09, 95% CI 0.07-17.14, p = 0.95), VTE (RR 0.35, 95% CI 0.08-1.49, p = 0.16) (Figure 2), and bleeding (RR 1.99, 95% CI 0.73-5.40, p = 0.18).

Conclusions:
Thromboprophylaxis with AC in outpatients with COVID-19 is not associated with reduction in the risk of hospitalization, death or VTE when compared with placebo.
Abstract 14449: Long-Term Colchicine for Cardiovascular and Limb Risk Reduction in Peripheral Artery Disease
Authors: Heindel Patrick , Fitzgibbon James J , Secemsky Eric A , Bhatt Deepak , Alomran Mohammed , Verma Subodh , Almaghlouth Ibrahim A , Madenci Arin , Hussain Mohamad A
Published: December 2023

Introduction:
Evidence from randomized trials suggests colchicine may reduce major adverse cardiovascular events (MACE) in patients with coronary artery disease. Colchicine's effect in lower extremity peripheral artery disease (PAD) is not known.

Methods:
To make inferences about the real-world effectiveness of colchicine in PAD, we emulated a pragmatic target trial, leveraging variable prescription durations when adding colchicine to urate lowering therapy in patients with gout and PAD. Eligible patients received care at a multicenter academic health system between July 2007 and December 2019. Electronic health records were linked to Medicare claims data. Patients received either colchicine indefinitely (long-term) or for 3 months (short-term) and the observational analog of the per-protocol effect was estimated. Inverse probability weighted marginal structural models were used to adjust for potential confounding, immortal-time, and collider-stratification biases. The primary outcome was a 2-year composite of major adverse limb events (MALE), MACE, and all-cause mortality.

Results:
A total of 1,025 patients were enrolled; mean age was 77 years (SD 7), 32% were female, and 9% were non-white race. The risk of the primary composite outcome at 2 years was 31.2% (95% CI 26.9, 35.2) in the long-term colchicine group and 32.7% (29.6, 36.4) in the short-term group (Figure), with a risk difference of -1.6% (-6.3, 3.4) and risk ratio of 0.95 (0.82, 1.11). Beyond 2 years, risk estimates of secondary outcomes in each group diverged, but confidence intervals also widened (Figure).

Conclusions:
In a real-world sample of high-risk patients with PAD and gout, estimates of the effect of colchicine provided no conclusive evidence that colchicine decreased the risk of adverse cardiovascular or limb events and death. The cardiovascular and limb benefits of colchicine in older comorbid populations with PAD and advanced systematic atherosclerosis remain uncertain.
Abstract 14450: Effects of SGLT2 Inhibitors in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials
Authors: Pessoa Fernando R , A de Moraes Francisco Cezar , Cavalcanti Souza Maria Eduarda , Rodrigues Anna , Pasqualotto Eric , Fernandes Isabela , Araujo Monteiro Antonio Maria Zacarias , Moraes de Souza Dilma do Socorro
Published: December 2023

Background:
Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are a class of drugs initially developed for the treatment of type 2 diabetes mellitus which demonstrated benefits in reducing cardiovascular complications. However, the benefits of using SGLT2i after acute myocardial infarction (AMI) still have limited evidence.

Research Questions:
Does the use of SGLT2i after percutaneous coronary intervention (PCI) due to AMI contribute to reducing mortality and hospitalization due heart failure (HF)?

Aims:
To assess the benefit of SGLT2i after AMI in patients undergoing PCI in reducing overall mortality, cardiovascular mortality and occurrence of HF.

Methods:
PubMed, Scopus, Cochrane Library and Web of science databases were searched for randomized controlled trials (RCTs) comparing SGLT2i with placebo after AMI in patients undergoing PCI. We computed risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). The heterogeneity was evaluated with I
2
statistics. R Software, version 4.2.1, was used for statistical analysis. The protocol was registered in PROSPERO (CRD42023424657).

Results:
A total of 4 RCTs with 1,311 patients, of whom 439 (33.48%) underwent SGLT2i therapy. The mean age was 60.2 (10.9) years in the SGLT2i group and 66.5 (13.8) years in the placebo group. Mean follow-up ranged from 23 to 96 weeks. In the pooled analysis, SGLT2i significantly reduced hospitalization due to HF (RR 0.39; 95% CI 0.20-0.75; p<0.01; I
2
=0%). There were no significant differences between SGLT2i and placebo regarding cardiovascular death (RR 0.52; 95% CI 0.23-1.18; p=0.12; I
2
=20%), non-cardiovascular death (RR 0.79; 95% CI 0.26-2.38; p=0.68; I
2
=0%) and all- cause death (RR 0.59; 95% CI 0.30-1.13; p=0.11; I
2
=12%).

Conclusion(s):
SGLT2i were associated with a reduction in hospitalization due to HF. However, no differences were found for cardiovascular, non-cardiovascular or all-cause deaths.
Abstract 14451: Switching From Warfarin to Direct Oral Anticoagulants (DOACs) in Medicine Clinic at a Safety Net Hospital in New York City: A Quality Improvement Project
Authors: Abdelmottaleb Wael , Ozbay Mustafa , Ghosh Kuldeep , Pathakamudi Poojitha , Delgado Lazo Victor , Al-Juboori Mohammed T , Mushiyev Savi
Published: December 2023

Introduction:
Many patients are still using warfarin for thromboembolic prevention, even though Direct-Acting Oral Anticoagulants (DOACs) have replaced it in most indications to decrease the need for frequent dose adjustments and minimize drug interactions.

Methods:
This study is a clinic patient-based observational quality improvement project to review warfarin use in adult patients following at the anticoagulation clinic at Metropolitan Hospital. Electronic medical records were screened, and TTR was calculated over 3 months. STATA was used for statistical analysis, including Histograms, Skewness-Kurtosis tests for normality, student-T tests for continuous variables, and χ2 tests for categorical variables. The P-value of less than 0.05 was considered statically significant.

Results:
A total of 45 patients were included; the mean age was 61, of whom 23 (51.1%) were males. The comorbidities observed were hypertension (HTN), diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), and obesity. The time in therapeutic range (TTR) was less than 65% in 22 patients (48.9%). Warfarin was indicated in 28 patients (62.2%) and not indicated in 17 patients (37.8%), out of which 6 patients (36.3%) agreed to switch to direct oral anticoagulants (DOACs) (Figure 1).

Conclusions:
Our project revealed a significant number of patients are still using warfarin despite being suitable for DOACs. 60% prefer warfarin due to perceived safety with frequent clinic visits. Socioeconomic status affects the transition. The PINNACLE Study identified practice and provider variations, Practices with high-volume clinics, more electrophysiologists, and those located in the western region are more likely to switch to DOACs. Based on our findings, we recommend the following: - Physicians should engage in shared decision-making with patients on warfarin use. - Physicians may need to discuss the available DOACs options with insurance companies due to coverage limitations.
Abstract 14453: Patent Foramen Ovale Closure in Patients With and Without Nickel Hypersensitivity Using Two Different Devices
Authors: Apostolos Anastasios , Gregoriou Stamatios , DRAKOPOULOU MARIA , Trantalis George , Chatzidimitriou Eleni , Tsalamandris Sotiris , Karmpalioti Maria , Synetos Andreas , Aggeli Constantina , Stratigos Alexander , Tsioufis Konstantinos , Toutouzas Konstantinos
Published: December 2023

Background:
Transcatheter PFO closure has been established as a safe and effective approach for secondary prevention in patients with ESUS. The Amplatzer® PFO occluder and Gore Helex® septal occluder are two FDA-approved devices, which consist of a nickel-titanium alloy frame. While nickel is the first cause of hypersensitivity reaction worldwide, the potential occurrence of nickel hypersensitivity following PFO closure is still under investigation.

Aim:
Our aim is to investigate whether patients with nickel allergy are more susceptible to experiencing adverse events after device implantation and to explore the potential role of device selection.

Methods:
We prospectively enrolled patients undergoing PFO closure. Before the procedure, nickel skin patch tests were performed in all the patients. The patients were randomized to receive either Amplatzer® or Gore® device. During a three-month follow-up period, we evaluated the primary endpoint, which was a composite outcome including patient-reported chest pain, palpitations, headaches, and rash. We used the chi-squared test to evaluate the primary endpoint and performed multivariate binary logistic regression analysis to assess the effect of device selection on the primary endpoint.

Results:
A total of 50 patients (50% female, 45.4±10.3 years old) completed the follow-up and were included in the present analysis. Among them, 29 patients received the Gore device, while the remaining 21 patients received the Amplatzer device. Fourteen patients were diagnosed with nickel hypersensitivity. The primary endpoint was reached in 40% of the analyzed patients. The occurrence of the primary endpoint was significantly higher in patients with nickel hypersensitivity compared to those without (50% vs. 13.3%, p=0.005). Additionally, multivariate binary logistic regression analysis demonstrated no association between device selection and the composite outcome (p=0.892).

Conclusions:
Our preliminary results indicate that patients with nickel hypersensitivity are more likely to develop symptoms such as chest pain, palpitations, headaches, and rash following the procedure. However, the completion of our study is necessary to obtain more reliable and conclusive results.
Abstract 14461: Impact of Intermittent vs Persistent Left Ventricle Outflow Tract Obstruction on Left Atrial Strain and Diastolic Function in a Young Hypertrophic Cardiomyopathy Cohort
Authors: Gearhart Addison , Epstein Sonia F , Gauvreau Kimberlee , Ferraro Alessandra M , Roth Ingrid , Mangano Christina M , Harrild David M , Colan Steven D , Chen Ming-Hui
Published: December 2023

Background:
Adolescents and young adults with hypertrophic cardiomyopathy (HCM) and persistent left ventricular outflow tract obstruction (LVOTO) have larger left atrial volume (LAV) and abnormal diastolic function and left atrial (LA) strain compared to those without resting LVOTO. It is unknown whether intermittent LVOTO with exercise results in smaller LAV and improved diastolic function and LA strain indices compared to persistent LVOTO.

Methods:
All HCM patients with echo and exercise stress echocardiography (ESE) from 2014-2022 at a single center were enrolled. The cohort was divided into 3 ESE hemodynamics groups: 1) No LVOTO (all gradients < 30 mmHg, n=48); 2) Intermittent LVOTO (no rest gradient, exercise ≥30 mmHg, n=41); 3) Persistent LVOTO (rest/exercise ≥30mm Hg, n=29). LAV (biplane method), LAV Z scores, LV lateral e’, lateral e’ Z scores, LA reservoir (LASr), conduit (LAScd), and contractile (LASct) strain (TOMTEC Arena AutoSTRAIN) were analyzed. For each parameter, mean values were compared across groups using one-way analysis of variance. The Bonferroni method was used to compare Group 2 to 1 and 3.

Results:
118 patients (31% F, median age 17 yrs, range 7-39) formed the cohort. Mean LAV was 64.9, 65.1, and 79.5 ml in Groups 1, 2, and 3 respectively. Differences in group means were found for LAV Z score, lateral e’, lateral e’ Z score, LASr, and LAScd (all p≤0.01). In Group 2 vs 3, LAV Z score was significantly lower (0.46 v 1.89) and LV lateral e’, lateral e’ Z score, and LAScd were significantly higher (lateral e’: 13.1 v 9.0 cm/s; lateral e’ Z score: -2.0 v -3.4; LAScd: 26.0 v 21.1%) (Fig 1). LASr did not differ significantly in Group 2 vs 3. No significant differences were found in Group 2 vs 1.

Conclusion:
In one of the largest young HCM cohorts, intermittent obstruction was associated with smaller LAV, better diastolic indices, and higher LA conduit strain versus persistent obstruction. Longer follow-up is needed to assess change as those with intermittent LVOTO age.
Abstract 14462: Baseline Characteristics of Tirzepatide-Treated Participants Who Shifted to a Normal Body Mass Index (<25 kg/m
2
): A Post Hoc Analysis From SURMOUNT-1
Authors: Srinath Reshmi , Sattar Naveed , He Xuanyao , Plat Arian , Falcon Beverly L , Stefanski Adam , Lee Clare J
Published: December 2023

Introduction:
Tirzepatide is a once weekly GIP and GLP-1 receptor agonist approved for the treatment of type 2 diabetes and under investigation for chronic weight management. In SURMOUNT-1, tirzepatide treatment resulted in substantial body weight reductions in people with obesity (body mass index (BMI) ≥30 kg/m
2
) or overweight (BMI ≥27 kg/m
2
).

Hypothesis:
This post hoc analysis assessed the baseline characteristics of tirzepatide-treated participants who reached normal BMI, defined by <25 kg/m
2
.

Methods:
Participants (N=1834) from SURMOUNT-1 with at least one post-baseline BMI measurements and adherent to tirzepatide (≥75% of doses received) were included in this analysis. The proportion of participants who shifted to a normal BMI was assessed during the study period. Baseline demographics and clinical characteristics were compared between participants who shifted to a normal BMI vs those who did not reach a normal BMI by week 72.

Results:
A total of 380 participants shifted to a normal BMI during the study period. Participants who shifted to a normal BMI were slightly older, more likely to be female, with shorter duration of obesity and lower baseline BMI (in particular a BMI ≥27 to <30 kg/m
2
or ≥30 to <35 kg/m
2
), HbA1c, fasting glucose, fasting insulin, systolic blood pressure, ALT and eGFR vs those who did not reach a normal BMI (Table). Additionally, fewer had prediabetes and hypertension, and a greater proportion of participants had dyslipidemia in those who reached the normal BMI vs those who did not.

Conclusions:
In this post hoc analysis from SURMOUNT-1, approximately one in five participants with overweight or obesity receiving tirzepatide treatment reached the normal BMI (<25 kg/m
2
) by week 72. Participants who reached the normal BMI were older, more likely to be female and had several favorable characteristics at baseline including lower baseline BMI, HbA1c, blood pressure, ALT and eGFR compared to those who did not reach the normal BMI.
Abstract 14464: Meta-Analysis Comparing Early vs Delayed Anticoagulation After Stroke in Patients With Atrial Fibrillation
Authors: Singh Sahib , Tantry Udaya , Ashley William W , Goel Swecha , Bliden Kevin , Gurbel Paul
Published: December 2023

Introduction:
Secondary prevention with anticoagulants is recommended for patients with acute ischemic stroke and atrial fibrillation (AF), but the timing of initiation of anticoagulation is debated. We performed a meta-analysis of the available studies.

Methods:
Studies comparing early (≤ 7 days) vs delayed (> 7 days) start of anticoagulation after acute stroke in patients with AF were searched from online databases. The primary endpoints of interest were recurrent ischemic stroke, intracranial haemorrhage (ICH), and mortality at the longest available follow up. Random-effects model was used to estimate risk ratios (RR) with 95% confidence intervals (CI).

Results:
Four studies (2 randomized trials and 2 observational studies), with a total of 5,606 patients - 2,918 in the early group and 2,688 in the delayed group were included. The mean age was 79 years and 55% of patients were men. The follow up duration varied from 30 days to 6 months. No significant differences were found between the early and delayed anticoagulation groups with regards to risk of recurrent ischemic stroke (RR 0.80, 95% CI 0.51-1.27, p = 0.35) (Figure 1), ICH (RR 0.62, 95% CI 0.17-2.24, p = 0.47) or mortality (RR 0.88, 95% CI 0.64-1.22, p = 0.45) (Figure 2).

Conclusions:
In patients with acute ischemic stroke and AF, early initiation of anticoagulation has similar risk of recurrent stroke, ICH, and mortality, when compared with delayed initiation.
Abstract 14482: Low Utilization of Guideline-Recommended Genetic and Pharmacogenetic Testing Among Patients With Cardiovascular Conditions in the United States (US)
Authors: DeHart Brady , Morin Pamela , Tucker Jamie , Spencer Scott , Bapat Bela , Trachana Kalliopi , Hostin Damon , Schroeder Brock , Belmont, MD,PhD John
Published: December 2023

Introduction:
Cardiovascular disease (CVD) continues to be the leading cause of death in the US and globally. Clinical practice guidelines recommend genetic testing for the diagnosis of select CVDs to improve disease management, reduce incidence of cardiac events, and positively impact major cardiac adverse events. Professional guidelines also recommend pharmacogenomic (PGx) testing for patients being prescribed certain medications.

Research Question:
What is the utilization of genetic diagnosis and PGx testing in patients with CVD in the US?

Methods:
This study used data from the Optum Labs Data Warehouse, composed of de-identified administrative claims data for both commercially insured and Medicare Advantage enrollees to assess rates of genetic testing among adult patients diagnosed with 4 major types of CVD conditions (arrhythmias (N=518,316), familial hypercholesterolemia (FH) (N=38,068), cardiomyopathies (CM) (N=74,597), and aortopathies (N=58,316)) and PGx testing rates in patients prescribed CVD medications with PGx test recommendations (per CPIC guidelines) between January 1, 2017 to December 31, 2021. Patients were required to have ≥12 months of continuous enrollment prior (baseline) to diagnosis (index date) and ≥12 months post-index period unless they died (follow-up). Genetic and PGx testing was captured using Current Procedural Terminology (CPT®) codes in both baseline and follow-up periods.

Results:
Low genetic testing utilization was found across the 4 major types of CVD conditions. Genetic testing rates were 1.3% in the arrythmia cohort, 1.9% in the CM cohort, 2.0% in the aortopathy cohort and 1.9% in the FH cohort. PGx testing rates in patients prescribed with CVD relevant medications were 0.6% (N=2,094/377,111) in the arrhythmia cohort, 0.8% (N=501/60,632) in the CM cohort, 0.7% (N=247/37,344) in the aortopathy cohort, and 1.3% (N=329/25,835) in FH cohort.

Conclusions:
Despite clinical practice guidelines, genetic and PGx testing in patients with CVD conditions remains underutilized. Future work will help us understand the barriers to guideline adherence both for genetic diagnosis and PGx testing that could impact clinical management and patient outcomes.
Abstract 14496: HIF2a Activation Reduces Pulmonary Angiogenesis and Promotes Vascular Remodeling in Pulmonary Arterial Hypertension by Suppressing Wnt7a Production in Pulmonary Endothelial Cells
Authors: Mitra Ankita , Yi Dan , Agarwal Stuti , Tian Amy , Jiang Xinguo , Nicolls Mark , Dai Zhiyu , Dejesus Vinicio A
Published: December 2023

Introduction:
Dysfunctional angiogenesis and obliterative vasculopathy are hallmarks of pulmonary arterial hypertension (PAH). Inappropriate HIF1a/2a activation and insufficient Wnt7a production are associated with pulmonary artery endothelial cell (PAEC) dysfunction, suggesting that HIF1a/2a and Wnt7a may interact as part of a signaling axis to promote PAEC homeostasis.

Hypothesis:
HIF1a/2a overactivation suppresses Wnt7a expression in PAH PAECs.

Methods:
Healthy and PAH PMVECs were obtained from explanted lungs. Cobalt Chloride (CoCl2) was used to activate HIF. PMVECs were transfected with lentiviruses carrying HIF1a/2a constructs, followed by functional and molecular studies. Lungs from mice with endothelial-specific HIF1a/2a activation (Egln1
Tie2Cre
) and HIF2a deletion (EH2) were analyzed via single cell (sc) RNA-seq and confocal imaging.

Results:
Compared to controls, PAH lung tissue and PAECs demonstrated an inverse correlation between increased HIF1a/2a, and reduced Wnt7a expression. Treatment with CoCl2 for 24 hours resulted in a ~4-fold increase in Wnt7a transcription that was absent in PAH PMVECs. Lentivirus transfection of healthy PAEC demonstrated that HIF1a increased Wnt7a transcription while HIF2a significantly reduced Wnt7a transcription. In silico analysis of the Wnt7a gene locus demonstrated HIF binding sites at promoter-enhancer sequences suggesting that Wnt7a is a gene target of HIF signaling. In addition, ATAC-seq and ChIP-seq analysis of the Wnt7a gene locus in PAH PMVECs indicated a closed chromatin configuration, suggesting epigenetic repression. Lung scRNA-seq and RNAScope analysis of Egln1
Tie2Cre
mice demonstrated a reduction of capillary EC, which was absent in EH2 mice, suggesting a HIF2a-dependent mechanism. Confocal and WB of lung tissues demonstrate that Wnt7a expression was significantly reduced in Egln1
Tie2Cre
mice but preserved in EH2 mice.

Conclusions:
HIF2a and epigenetic repression contribute to PAEC dysfunction by suppressing Wnt7a-dependent angiogenesis in PAH. We speculate that Wnt7a may also be required to maintain the capillary EC phenotype in the lung and that restoring Wnt7a production could compensate for HIF-driven endothelial dysfunction in PAH.
Abstract 14505: BSCL2/Seipin Deletion Rescues ATGL-Deficiency-Induced Lethal Lipotoxic Cardiomyopathy
Authors: Zhou Hongyi , Su Huabo , Li Ji , Chen Weiqin
Published: December 2023

Imbalances in triglyceride (TG) catabolism are associated with cardiac lipid deposition and contractile dysfunction, as manifested in patients with primary triglyceride deposit cardiomyovasculopathy (TGCV) caused by adipose triglyceride lipase (ATGL) deficiency. BSCL2/Seipin is a highly conserved endoplasmic reticulum protein widely implicated in lipid droplet biogenesis and TG metabolism. We previously reported that global

Bscl2
–/–

mice and mice with cardiac-specific deletion of
Bscl2
manifest higher myocardial ATGL expression and develop mild cardiomyopathy with reduced cardiac steatosis. However, the interplay between BSCL2 and ATGL in hearts remains to be further interrogated. In this study, we surprisingly discovered that global BSCL2 deletion completely rescued the lethal lipotoxic cardiomyopathy in the genetic ATGL-deficient TGCV model (

Atgl
–/–

mice) by drastically reducing cardiac TG deposits, abolishing cardiac hypertrophy, and restoring cardiac contractility. Transcriptomic analyses identified the elevated inflammatory, oxidative stress, and extracellular matrix pathways in

Atgl
–/–

hearts, which were dramatically ameliorated by BSCL2 deletion. Conversely, the severely suppressed cardiac metabolic functions, muscle contraction, and ion transport pathways in

Atgl
–/–

hearts were also normalized by BSCL2 deletion. Heatmap data further revealed that the mRNA levels of
Pgc1/Ppara
and fatty acid oxidation (FAO) genes were not altered in

Bscl2
–/–

hearts but were severely repressed in

Atgl
–/–

hearts due to defective TG lipolysis. However, their expressions in

Atgl
–/–
Bscl2
–/–

hearts were restored to similar levels as wild-type

and Bscl2
–/–

hearts. RT-PCR analyses further confirmed such changes. Notably, cardiac-specific deletion of BSCL2 rescues lethal cardiomyopathy in mice with cardiac-specific deletion of ATGL. These data suggest that cardiac BSCL2 cell-autonomously regulates ATGL-independent TG hydrolysis and FAO pathways essential for cardiac function. Our study highlights the presence of BSCL2-mediated ATGL-independent pathways that regulate cardiac TG metabolism and provide novel therapeutic approaches to treat ATGL-deficiency-associated lethal cardiomyopathy.
Abstract 14510: Precision Phenotyping of Social Determinants of Health and Risk of Coronary Disease, Heart Failure, and Stroke: The Jackson Heart Study
Authors: Zierath Rani , Lamberson Victoria , Yang Yimin , Claggett Brian , Hall Michael E , Spruill Tanya M , Floyd James S , Odden Michelle C , Sims Mario , Shah Amil M
Published: December 2023

Introduction:
While social determinants of health (SDOH) are associated with cardiovascular disease (CVD) risk, limited data exist regarding their interrelated impact on distinct CVD events.

Methods:
Among 4,164 Black adults in the Jackson Heart Study (JHS) free of prevalent coronary disease (CHD), heart failure (HF), and stroke at baseline (2000-2004), we used consensus clustering - an unsupervised class discovery and validation approach - to identify subgroups of participants based on 9 SDOH measures reflecting the Healthy People 2030 framework: income, education, discrimination, food insecurity, healthy food stores within 1 mile, healthcare access, neighborhood violence, neighborhood disadvantage, and air pollution (PM2.5). We used multivariable Cox proportional hazards models to relate cluster membership to risk of incident CHD, HF, and stroke adjusting for age, sex, hypertension, diabetes, obesity, and chronic kidney disease.

Results:
Mean age was 55 ± 13 years and 63% were women. We identified 4 participant clusters with differential exposure to SDOH: Cluster 1 (n=1359) had the most favorable SDOH profile with highest income and lowest neighborhood disadvantage and violence; Cluster 2 (n=915) had highest PM 2.5 and lowest frequency of food stores; Cluster 3 (n=998) had lowest education level and highest neighborhood disadvantage and violence; and Cluster 4 (n=820) had lowest income and healthcare access and highest prevalence of food insecurity. Over a median of 11 [IQR 10 - 11] years, 255 participants developed HF, 159 CHD, and 167 stroke. Compared to Cluster 1, Clusters 3 and 4 were associated with higher risk of incident HF while Clusters 2 and 3 were associated with higher risk of stroke (
Figure
). Cluster membership was not associated with risk of CHD.

Conclusions:
Multiparametric SDOH assessment identifies unique clusters of individuals differentially burdened by individual-level social determinants and at heightened risk for distinct CVD events.
Abstract 14561: Utility of TAPSE/RVSP Ratio in Predicting Severity of Pulmonary Hypertension and Survival in the PVDOMICS Cohort
Authors: Ali Ambreen F , Goff Zackary D , Yu Shilin , Jacob Miriam , Kwon Deborah H , Frantz Robert , Jellis Christine L ,   the PVDOMICS Study Group
Published: December 2023

Introduction:
The right ventricle [RV] adapts to pulmonary hypertension [PH] by increasing contractility to maintain RV-PA coupling. With increased afterload, RV contractility cannot compensate, resulting in RV failure. TAPSE/RVSP ratio is a non-invasive measure of RV-PA coupling. We aim to assess TAPSE/RVSP ratio for predicting PH severity and survival across a spectrum of PH in the PVDOMICS cohort.

Methods:
PVDOMICS subjects from the 5 World Symposium PH groups and comparators were evaluated. TAPSE/RVSP ratio, in mm/mmHg, was derived for each group. PH subjects were stratified by TAPSE/RVSP ratio into low < 0.19, intermediate ≥ 0.19 to < 0.32, and high ratio
>
0.32. The relationship between the ratio and RHC parameters (mean PA pressure [mPAP] and pulmonary vascular resistance [PVR]), and between-group differences were evaluated by one-way ANOVA. Kaplan-Meier curves and log-rank tests were used to characterize and compare survival between groups.

Results:
Data were available for 514 PH subjects (58 ± 15 yrs, 64% female) and 179 comparators (61 ± 13 yrs, 59% female). Mean TAPSE/RVSP ratio was 0.35 ± 0.18 in PH vs 0.63 ± 0.26 in comparators (p < 0.001). Mean TAPSE/RVSP across the PH groups 1-5 were similar, 0.33 ± 0.19, 0.33 ± 0.16, 0.37 ± 0.15, 0.41 ± 0.21 and 0.43 ± 0.29 (p=NS). Within PH subjects, 99 (19.2%) had low, 173 (33.7%) had intermediate and 242 (47.1%) had high ratio. Those with low ratio had higher mPAP (53.6 ± 11.8 mmHg), compared to intermediate (44.6 ± 11.7 mmHg) and high ratio (34.1 ± 10.2 mmHg) [p < 0.001]. Those with low ratio had higher PVR (10.1 ± 5.1 WU), compared to intermediate (6.8 ± 4.1 WU) and high ratio (4.1 ± 2.1 WU) [p < 0.001]. Survival was significantly higher for those with high TAPSE/RVSP ratio compared to those with low ratio (p < 0.001) [Figure].

Discussion:
TAPSE/RVSP ratio correlates well with invasive markers to predict PH severity. This useful measure of RV-PA coupling also enables stratification for outcome, with ratio
>
0.32 having the best survival rates.
Abstract 14566: Long-Term Efficacy of Evolocumab in Patients With and Without Multivessel Coronary Artery Disease
Authors: McClintick Daniel J , O'Donoghue Michelle L , De Ferrari Gaetano Maria , Ferreira Jorge M , Ran Xinhui , Im KyungAh , Lopez J. A , Elliott-Davey Mary , Wang Bei , Monsalvo Maria Laura , Atar Dan , Keech Anthony , Giugliano Robert P , Sabatine Marc S
Published: December 2023

Background:
In FOURIER, the magnitude of reduction in risk of major adverse cardiovascular events (MACE) was larger in patients with multivessel disease (MVD) than in those without. However, the median follow-up was only 2.2 yrs. The open-label extension (FOURIER-OLE) allows for a better assessment of the long-term benefit of intensive lipid-lowering in these two subgroups.

Methods:
Patients with CAD at time of enrollment in the parent FOURIER trial were categorized based on the presence or absence of MVD (≥40% stenosis in ≥2 large vessels). Primary endpoint (PEP; CV death, MI, stroke, hospitalization for UA, or coronary revascularization) and key secondary endpoint (SEP; CV death, MI, or stroke) were assessed through FOURIER and FOURIER-OLE, during which all patients received evolocumab.

Results:
At enrollment in FOURIER, 23,674 patients had CAD, of whom 25% had MVD (N=6007). In the placebo arm, those with MVD had a higher risk of the PEP (HR 1.45 [95%CI 1.32-1.60], P<0.0001) & SEP (HR 1.37 [1.22-1.56], P<0.0001) than those without MVD. The magnitude of the overall relative risk reduction in those initially randomized to evolocumab tended to be greater in patients with MVD than in those without (RRR 23% vs. 12% for PEP; 30% vs. 15% for SEP; P
int
0.07 & 0.04, respectively). The magnitude of benefit tended to grow over the first several years (Fig). This was especially true for CV death, in which for patients with MVD, initial randomization to evolocumab reduced the risk of CV death in the later years (HR 0.70 [0.51-0.97]; Fig bottom).

Conclusion:
Evolocumab reduced the rate of MACE in patients with and without MVD, with earlier and larger benefit seen in patients with MVD. The magnitude of benefit grew over time, supporting early initiation of intensive LDL-C lowering both in patients with and without MVD.
Abstract 14574: Trends in the Utilization of Sacubitril/Valsartan by Cardiologists: A Safety-Net Hospital Experience
Authors: Sawalha Khalid , Smith Andrew , Norgard Nicholas , Lopez-Candales Angel
Published: December 2023

Background:
Sacubitril/Valsartan has gained significant momentum regarding management of heart failure. In the latest 2022 HF guideline, Sacubitril/Valsartan is recommended as a first-line treatment and to replace well-tolerated ACEi/ARB’s. We decided to evaluate current utilization trends with regards to prescription of Sacubitril/Valsartan at our safety-net hospital.

Methods:
For this retrospective study,a chart review identified Sacubitril/Valsartan use in a total of 769 patients,which was catalogued by drug dose, division use, and prescriber specialty at University Health Truman Medical Center in Kansas City, Missouri from October 1, 2021 thru October 31, 2022.

Results:
Of the 769 patients prescribed Sacubitril/Valsartan, 497 patients were prescribed the 24 mg/26 mg dose, 193 patients were on 49 mg/51 mg dose, and 79 patients were provided a 97 mg/103 mg dose (Figure 1). Cardiologists were only involved in 23% of all Sacubitril/Valsartan prescriptions while ancillary staff providers including nurse practitioners, physician assistants and pharmacists representing the predominant number of healthcare professionals (50%) prescribing Sacubitril/Valsartan (Figure 2).

Conclusion:
Despite the robust evidence supporting the benefit of using Sacubitril/Valsartan in HF and the unique opportunity that Cardiologists have in taking ownership in optimizing HF management; our data seems to suggest that prescription rates of Sacubitril/Valsartan by Cardiologists at our institution remains low when compared to other specialties. This may contribute to an undertreatment of high-risk HF patients.
Abstract 14595: Leveraging Deep Learning to Elucidate Subclinical Aortic Stenosis Risk
Authors: Kany Shinwan , Rämö Joel , Hou Cody , Jurgens Sean J , Nauffal Victor , Cunningham Jonathan , Lau Emily , Butte Atul , Ho Jennifer E , Olgin Jeffrey , Elmariah Sammy , Lindsay Mark E , Ellinor Patrick T , Pirruccello James
Published: December 2023

Background and Aims:
Aortic stenosis (AS) is associated with a high global burden of morbidity. Current guidelines do not fully define normal aortic valve (AV) function or mild AS. We aimed to study normal variation in AV function and address current gaps in knowledge.

Methods:
We developed a deep learning model to study velocity-encoded magnetic resonance imaging (MRI) in 47,223 UK Biobank participants. We calculated aortic valve area (AVA), peak velocity (PV), and mean gradient (MG).

Results:
In healthy individuals, we found an annual decrement of 0.03 cm2 in AVA. Normal variation in AV function was predictive of future AV surgery (HR 2.4 per SD increase in PV, P2.6E-110), heart failure (HR 1.23 per SD, P=2.4E-07), and coronary disease (HR 1.23 per SD, P=2.0E-14). Risk was still elevated when excluding participants with moderate-to-severe AS. We determined thresholds for abnormal AV function as being >95% for all age groups in 31,909 healthy people. This established the boundary between normal variation and mild AS as any of: PV >1.65m/s, MG >4.9mmHg, and AVA <2.1cm2 (men) or <1.7cms2 (women). A total of 3,288 participants (7.0%) met the definition of mild AS which was associated with high risk for AV surgery (HR 57.2, P=4.4E-29). Over a mean 3.1±2.0 years of follow-up, the incidence of AV surgery was 0.02% in those with normal AV function and nearly 20% among participants with MG ≥10mmHg. Greater levels of ApoB, triglycerides, Lp(a), and inflammatory markers were associated with higher AV gradients.

Conclusion:
In this study, we report the largest analysis of AV function and cardiovascular disease in the general population with MRI using deep learning. We propose thresholds to define the lower bounds of mild AS and demonstrate a step change in cardiovascular risk between normal AV function and mild AS. Atherogenic and inflammatory biomarkers were associated with increased AV gradients. These findings may inform earlier surveillance and efforts to prevent complications of AS.