bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14063: Eight Pharmacokinetic-Related Genetic Variants Were Not Associated With Bleeding From Direct Oral Anticoagulants in Non-Valvular Atrial Fibrillation Patients
Authors: Campos-Staffico Alessandra M , Dorsch Michael P , Barnes Geoffrey , Zhu Haojie , Limdi Nita , Luzum Jasmine A
Published: June 2023

Background.
Atrial fibrillation (AF) is the leading cause of ischemic stroke and treatment has focused on reducing stroke risk through anticoagulation. Direct Oral Anticoagulants (DOACs) are the first-line guideline-recommended therapy in non-valvular AF since they are as effective and safer than warfarin. Although patients bleed less overall from DOACs, bleeding still is the main safety concern with this therapy. Previous studies have shown that genetic variants modify the function of metabolic enzymes or transporters involved in the pharmacokinetics (PK) of DOACs, which then affect DOAC plasma concentrations. However, whether those functional PK genetic variants are significantly associated with the risk of bleeding on DOACs is unknown.
Aim.
Assess the association of PK-related single nucleotide variants (SNVs) with the risk of bleeding from DOACs in non-valvular AF patients.
Methods.
A retrospective cohort study was carried out with 2,364 Caucasians with non-valvular AF and treated with rivaroxaban or apixaban. Patients were genotyped as part of the genomic biobank at the University of Michigan Health System. The primary endpoint was a composite of major and clinically relevant non-major (CRNM) bleeding. Cox proportional hazards regression with time-varying analysis assessed the association of 8 SNVs in 5 PK genes (
ABCB1
,
ABCG2
,
CYP3A4
,
CYP3A5
,
CYP2J2
) with the risk of bleeding from DOACs in unadjusted and covariate-adjusted models. Six tests were performed as 3 of the SNVs are in the same haplotype. P-values below the Bonferroni-corrected level of 8.33e-3 were considered statistically significant.
Results.
A total of 412 (17.4%) major and CRNM bleeding events occurred over 2.27 ± 2.03 years of follow-up. None of the PK SNVs were significantly associated with bleeding risk on DOACs (Table 1).
Conclusion.
SNVs that affect the function of PK genes were not significantly associated with major and CRNM bleeding from rivaroxaban or apixaban in 2,364 AF patients.
Abstract 14070: Role of Early Aortic Valve Replacement versus Conventional Management in Asymptomatic Patients With Severe Aortic Stenosis: A Meta-Analysis
Authors: Kaur Arpanjeet , dhaliwal arshdeep , Sohal Sumit , Balboul Yoni , Tamis-Holland Jacqueline
Published: June 2023

Introduction:
Aortic-valve replacement (AVR) is an effective therapy for patients with severe symptomatic aortic stenosis (AS) but the appropriate timing of intervention for asymptomatic patients with severe AS remains controversial. Increased mortality associated with the onset of symptoms challenges the conventional “watchful waiting” strategy followed for this subset of patients. An early intervention may be warranted, however the data supporting this hypothesis is small. Our aim was to perform meta-analysis looking at outcomes of early surgical AVR (SAVR) in asymptomatic severe AS patients with preserved LVEF.

Methods:
Electronic databases were searched for studies comparing early SAVR and conventional treatment in patients with asymptomatic severe AS and normal LV function. The primary outcome of interest was all cause mortality. Secondary outcome was heart failure hospitalization. Random-effects model was used to estimate the pooled risk ratio (RR), and 95% confidence interval (CI) using Revman 5.4.1. Subgroup analysis stratified by study design was performed. Heterogeneity was assessed by Higgins I
2
statistic.

Results:
We found total of 8 studies (2 RCTs; 6 observational) from which 2669 patients with asymptomatic severe AS were identified. 1354 underwent SAVR and 1315 were managed conservatively. The mean age was 68 years with mean follow up duration of 4.8±2 years. There was statistically significant reduction in all-cause mortality (RR: 0.37; CI: 0.27-0.50; p<0.05; I2 = 68%) and heart failure hospitalization (RR: 0.24; CI: 0.16-0.36; p<0.05; I2 = 0%) among patients who underwent AVR compared with conservative treatment with subgroup analysis by study design showing similar trends.

Conclusion:
Our meta-analysis shows that compared with conventional treatment strategy, early SAVR in asymptomatic patients with severe AS is associated with improved long-term outcomes notably reduced all cause mortality and heart failure hospitalizations.
Abstract 14078: Exercise Pulmonary Impedance and Coupling Stress Test, and MRI-Based Regional Strain Analysis: Identifying Afterload-Sensitive Phenotypes in PH-HFpEF
Authors: Raza Farhan , Lechuga Christopher , Seiter Daniel , Korcarz Claudia E , Eldridge Marlowe , Nagpal Prashant , Bluemke David , Wieben Oliver , Chesler Naomi
Published: June 2023

Objectives:
In pulmonary hypertension associated with HFpEF (PH-HFpEF), identifying mechanisms of right ventricular: pulmonary arterial (RV:PA) uncoupling can be leveraged for sub-phenotyping and targeted therapies. In this study, we aim to distinguish mechanisms of RV:PA uncoupling in PH-HFpEF due to high RV afterload (afterload-sensitive; AS) and impaired left ventricular-interventricular septal contributions to RV function (ventricular interdependence; VI).

Methods:
Subjects (n=13) with early-stage PH (per echo) and NYHA II-III dyspnea were prospectively enrolled. Exclusion criteria: advanced disease with NYHA IV, LVEF <50%. All subjects underwent rest-to-exercise (every 25 watts) invasive cardiopulmonary exercise test and echo (for impedance: characteristic for pulsatile load Z
C
, input for steady load Z
0
), followed by RV real-time pressure volume (PV)-loops. Subsequently, a cardiac MRI was performed with temporal resolution of 25-30 msec. Five study subjects had isolated post-capillary (Ipc-PH), 5 had pulmonary arterial hypertension, 2 had combined pre/post-capillary PH, and 1 had no PH.

Results:
With exercise, impedance (Z
C
and Z
0
) increased or remained unchanged in all PH subjects but decreased in the subject with no PH. Z
C
(time domain method) was correlated with PV-loop based uncoupling (end-systolic to elastance ratio Ees:Ea) among Ipc-PH subjects (r
2
=0.40, p<0.01), but had poor correlation in other phenotypes (r2=0.01, p=0.11). As next step, within each IpcPH subject, correlation of Z
C
with Ees:Ea (with repeated measures across exercise stages) was determined to identify afterload sensitivity (Figure). Cardiac MRI-based regional strain was used to identify ventricular interdependence; defined as reduced strain of interventricular septum (Figure).

Conclusions:
Multimodality methods to assess RV:PA uncoupling in PH-HFpEF can identify afterload-sensitive phenotypes, which may benefit from focused interventions.
Abstract 14087: Mitral Annular Calcification and Non-Cardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis
Authors: Oni Ebenezer , Boakye Ellen , Pressman Gregg S , Dardari Zeina , Jha Kunal , Szklo Moyses , Budoff Matthew J , Nasir Khurram , Blaha Michael J
Published: June 2023

Introduction:
Mitral annular calcification (MAC) may be a maker for biological aging. A few studies have showed an association with non-cardiovascular events. We evaluated the association of MAC presence and severity with incident renal failure (RF) and incident dementia in a multiethnic population.

Methods:
We used data from 6,814 participants in the Multi-Ethnic Study of Atherosclerosis without cardiovascular disease at baseline [53% females, mean age 62 ±10 years; 12% Chinese, 38% White, 22% Hispanic, 28% African American]. MAC [absent/present; 0, 1-99, and ≥100; and <100/≥100 Agatston Units (AU)] was assessed with non-contrast cardiac CT at study baseline. Using multivariable-adjusted Cox proportional hazard regression, we evaluated the association of MAC with RF and incident dementia defined by dementia hospitalizations/death.

Results:
MAC prevalence was 9.5%; 10.7% in women; 8.0% in men. After a mean follow-up of 13 ± 4 years, individuals with MAC had a higher incidence rate of RF when compared to those without (17.9 vs. 8.1 per 1000 person-years). The incidence rate of RF increased with increasing MAC severity - MAC = 1-99 and MAC ≥ 100 (14.7 and 22.2 per 1000 person-years, respectively). Compared to individuals without MAC, those with MAC ≥100 had a higher multivariable-adjusted risk of RF [Hazard Ratio (HR): 1.41; 95%CI: 1.07 - 1.84;
Table 1A
). Also, persons with MAC had a higher incidence of dementia when compared to those without MAC (16.4 vs. 4.1 per 1000 person-years). Persons with MAC = 1-99 AU (HR: 1.38; 95%CI: 1.01 - 1.89) and MAC ≥100 AU (HR: 1.71; 95%CI: 1.25 - 2.33) had significantly higher hazards of incident dementia than those without MAC (
Table 1B
).

Conclusion:
MAC is independently associated with incident renal failure and dementia in this multiethnic cohort. These findings underscore the utilization of MAC as an important marker of aging and risk of non-cardiovascular outcomes.
Abstract 14105: Stent Ahoy: Ventricular Tachycardia Due to Stent Migration Into the Right Ventricle
Authors: Hasnie Ali , Fischer William , Khitha Jayant
Published: June 2023

Case:
A 46-year-old female with PMHx of ESRD on dialysis and prothrombin gene mutation presented with acute onset of left breast swelling, redness and pain for nearly 24 hours. She was found to have SVC occlusion and underwent successful SVC recanalization and stent placement with an uncovered 14x40 mm nitinol stent. She presented 4 days later with complaints of chest pain and shortness of breath. Initial vitals were notable for tachypnea with oxygen saturations of nearly 70%, and a blood pressure of 114/71 mmHg. Physical exam demonstrated an obese female in distress. Shortly after arrival in the emergency department, she developed a non-sustained episode of ventricular tachycardia (NSVT). Amiodarone and lidocaine were started, however, she continued to have runs of NSVT. Initial CXR found no acute process but failed to demonstrate the previously placed SVC stent. ECG demonstrated normal sinus rhythm with frequent PVCs and runs of NSVT. A limited echo demonstrated a free edge of an endovascular stent within the right ventricle. TEE demonstrated the stent appeared to be tethered to the septal leaflet of the tricuspid valve with the leading edge free within the right ventricle. Endovascular retrieval was proposed but given the degree of entanglement within the tricuspid leaflets, large stent size, and recurrent NSVT, was deemed an unsuitable therapeutic strategy. Urgent open-heart surgery was performed for removal. The patient tolerated the procedure well and had no further recurrence of NSVT.

Discussion:
Stent migration is a rare but feared complication of venous stent deployment, with only 32 reported cases over the past 30 years. While NSVT is often attributed to the RVOT, the etiology being the result of migrated stents has been rarely reported. This is the first case to our knowledge of SVC stent migration leading to runs of NSVT.

Conclusion:
Clinicians must remain cognizant of the risk for venous stent migration and unusual clinical presentations resulting from migration.
Abstract 14108: Cisplatin-Induced Cardiac Macrophage Inflammatory Programs Unveiled With Single Cell Sequencing
Authors: Pan Hua , Song XueYing , Rajewski Alex , Wickline Samuel A
Published: June 2023

Introduction:

Cisplatin is used broadly in first-line chemotherapy regimens prescribed to ~20% of cancer patients. It is known that cisplatin treatment induces inflammatory cardiotoxicity, but the specific molecular sequellae in resident or trafficking cardiac macrophages remain to be elucidated. We hypothesized that single cell analysis of cardiac macrophage populations after cisplatin treatment would shed new light on the molecular mechanisms of inflammation in the heart induced by the cisplatin treatment and suggest new approaches to mitigate cisplatin induced cardiotoxicity.

Methods:

A mouse model was generated by i.p. injection of 25 mg/kg cisplatin to C57BL/6 mice. Saline injection served as control. Hearts were collected 48 hours post injection and single cell suspensions were produced before libraries were created using 10X genomics Chromium Next GEM Single Cell 3’ Reagent Kits (v3.1) before sequencing. CellRanger was used for processing single cell RNASeq outputs, followed by secondary Seurat analysis and DEG, KEGG pathway and TRANSFAC analysis on macrophages.

Results:

DEG analysis demonstrated that cisplatin treatment significantly inhibited expression of MHC class II-associated genes (H2-AB1, H2-EB1, H2-AA, H2-DMA, H2-DMB1) (Fig A and B). KEGG pathway analysis suggested that cisplatin treatment upregulated genes involved in IL-17 signaling pathway (LCN2, S100a9, S100a8) (Fig C and D). TRANSFAC analysis identified NF-κB as the only significantly upregulated transcription factor caused by cisplatin treatment with predicted binding sites of KCCAGANWN (NF-1B), GGGANTTTCCNN (RelA-p65), and KGGRNTTTCCC (RelA-p65).

Conclusions:

Reduced MHC-II gene expressions by cisplatin might upregulate self-repair pathways to promote macrophage efferocytosis and wound healing. The pro-inflammatory NF-κB and IL-17 signaling pathways represent potential therapeutic targets for mitigating cisplatin induced cardiac inflammation.
Abstract 14129: The Association of Sarcopenic Obesity and Increased Arterial Stiffness
Authors: Matsumoto Chisa , Tomiyama Hirofumi , Matsuura Mari , TAKAMIYA SHIORI , Nakano Hiroki , Shiina Kazuki , Yamashina Akira
Published: June 2023

Introduction:
Both sarcopenia and obesity have been regarded as risk factors of cardiovascular disease (CVD). However, inconsistent results of the association between sarcopenic obesity (SO) and risk of CVD have been reported. Also, no studies evaluated the association of SO and arterial stiffness, a marker of CVD. The objective of this study is to evaluate the association of SO and arterial stiffness.

Hypothesis:
We hypothesized SO is associated with increased arterial stiffness.

Methods:
Japanese Subjects above 50 years old who underwent annual health-checkup were enrolled in this cross-sectional study. Subjects with history of CVD and dementia were excluded. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). Obesity was defined as visceral fat over 100 cm2 evaluated by abdominal computed tomography. We evaluated sarcopenia by screening locomotive syndrome assessed by the questionnaires (GLFS-25) and physical performance tests consisted of those for a two-step test and a stand-up test according to the guidance of the Japanese Orthopedic Association. We defined SO as a combination of obesity and sarcopenia. The associations of SO, obesity, sarcopenia and baPWV were assessed by multivariable linear regression analysis adjusted for conventional CVD risk factors.

Results:
We categorized total 137 subjects (mean age: 59±6 years) into four groups; subjects with SO (N=28), only sarcopenia (N=37), only obesity (N=2), and none of them (N=43). BaPWV in subjects with SO was highest compared to other three groups (Figure, p=0.048). Multivariable linear regression analysis revealed that SO, sarcopenia, obesity, were gradually associated with increased arterial stiffness independent of CVD risk factors including lipid and glucose metabolism. (β=48±20, p=0.01).

Conclusion:
SO was associated with increased arterial stiffness independent of conventional CVD risk factors. Further research on SO and CVD is warranted.
Abstract 14137: SARS-CoV-2 Spike Protein-Induced Inflammation Underlies Proarrhythmia in COVID-19
Authors: Mezache Louisa , Nuovo Gerard , Suster David , Tili Esmerina , Awad Hamdy M , Radwanski Przemyslaw , Veeraraghavan Rengasayee
Published: June 2023

Cardiac manifestations are common in severe Coronavirus disease 2019 (COVID-19) with rates reported from 2% in non-ICU patients to 59% in non-survivors. Recent CDC data show that COVID-19 patients are at 1.7 higher risk of arrhythmia. AF, which is the most common arrhythmia, is a frequent complication of acute and long COVID-19. It has been reported that the SARS-CoV2 receptor, ACE2, is highly expressed in the heart, leading to the prevalent assumption that infectious virus likely underlies cardiac complications. However, the pathophysiology of cardiac disease in severe COVID-19 has yet to be clarified. We therefore compared the histologic and molecular findings in human cardiac tissue from fatal COVID-19 cases and age-matched controls. Hematoxylin and eosin (H&E) stains revealed histologic changes in the COVID-19 samples, most notably multifocal endothelial cell swelling and degeneration plus microvascular thrombi. Distribution of SARS-CoV2 RNA and nucleocapsid protein expression was investigated by qRT-PCR and
in situ
hybridization (ISH). Trace amounts of viral RNA and no nucleocapsid protein were detected in the COVID-19 hearts. However, 7/11 COVID-19 hearts were positive for viral spike protein. Further validation by immunohistochemistry (IHC) showed that viral spike protein was detected in all 11 COVID-19 hearts. Co-expression analysis revealed that viral spike protein localized mostly to the ACE2+ interstitial macrophages/pericytes that were activated as evidenced by increased IL6 and TNFα expression. Previously, we identified a novel arrhythmia mechanism wherein inflammation-induced vascular endothelial dysfunction triggers cardiomyocyte structural remodeling, particularly of intercalated disc (ID) components including connexin-43 (Cx43) gap junctions and Na
V
1.5 sodium channels, and thereby promotes arrhythmias. We therefore investigated ID structure in our human samples. Both Cx43 and Na
V
1.5 showed marked lateral migration in myocytes of COVID-19 hearts, consistent with previous experiments with inflammatory insults in murine hearts. These findings suggest that the viral spike protein, and not direct infection by SARS-CoV2, results in the pathophysiology of cardiac dysfunction in fatal COVID-19.
Abstract 14139: Differential Benefit of Non-Invasive Cardiac Stress Testing by HEART Score Risk Stratification
Authors: Kawatkar Aniket A , Sharp Adam , Baecker Aileen , Redberg Rita F , Lee Mingsum , Ferencik Maros , Goodacre Steve , Thokala Praveen , Wu Yi-Lin , Shen Ernest , zheng chengyi , Musigdilok Visanee , Sun Benjamin
Published: June 2023

Introduction:
AHA guidelines recommend non-invasive cardiac testing (NIT) within 72 hours after an emergency department (ED) evaluation for suspected acute coronary syndrome (ACS), after acute myocardial infarction (AMI) has been excluded. However, the effectiveness of this strategy to reduce the risk of future AMI or death, in low-risk patients is contested.

Hypothesis:
We hypothesized that in patients with low risk based on history, electrocardiogram, age, risk factors and troponin (HEART) based scoring, early NIT may not be beneficial compared to higher risk.

Methods:
We compared the effectiveness of early NIT vs. no early testing, in a retrospective cohort of adult (age ≥18) members of the Kaiser Permanente Southern California health system from 05/2016-12/2020. We included all adults presenting at EDs with suspected ACS and who had data to compute HEART score. We stratified the cohort into low risk (score 0-3); intermediate risk (score 4-6) and high-risk (score ≥7) based on HEART score. Within each group, confounder adjusted instrumental variables models were used to evaluate the marginal effect of early NIT, and the number needed to treat (NNT) was calculated as the inverse of the absolute composite risk reduction in death/AMI within 30 days of ED discharge.

Results:
The cohort included 174,936 patients [61% Low risk (mean age 53; female 58%; early NIT 5%), 36% intermediate risk (mean age 71; female 72%; early NIT 18%), and 3% high risk (mean age 74, female 45%; early NIT 23%)]. The risk reduction in 30-day death/AMI due to early NIT increased progressively through the intermediate-risk (NNT = 59) and high-risk groups (NNT = 24) (Table 1). Risk reduction in the low-risk group was not statistically significant.

Conclusions:
HEART score based high risk patients may benefit the most from early NIT. However, the majority of the suspected ACS cohort was classified as low risk and the benefit of early NIT on 30-day death/AMI was uncertain in this low-risk group.
Abstract 14140: Efficacy of Coronary Intravascular Lithotripsy Therapy on Severely Calcified Coronary Stenoses
Authors: Jadhav Kartik P , maddury srinivasa r , Kavalipati Narasaraju , Challawar Kapil , Gollamandala Kondalrao , Ali Syed Akram
Published: June 2023

Introduction:
Intravascular lithotripsy (IVL) is rapidly proving its effectiveness in modifying calcific coronaries. IVL causes cracks in calcium with acoustic waves Fig1 (A-D).

Hypothesis:
IVL is effective in calcific coronary artery modification.

Methods:
Study aims to assess the effectiveness in calcific coronary artery modification. This study is a prospective, single arm single center study designed to assess the effectiveness of the IVL. The primary endpoint is to determine the extent of procedural success. The calcium modification is assessed by optical coherence tomography (OCT). Based on OCT imaging the percentage of stent expansion after IVL was categorized into ‘Optimal’ and ‘Suboptimal’ and ‘Subpar’ outcomes.

Results:
Patients (n:26; M:17; F:9) were enrolled in last 6 months. IVL was used in 22 LAD (84.6%) and 4 RCA (15.4%). Mean calcified segment length was 33.8 mm, mean angle of calcium arc was 202.3 degrees and superficial calcific lesions were 5 out of 26 (19.2%). OCT demonstrated multiplane and longitudinal calcium fractures after IVL in all (100%) lesions. There were no subpar outcomes among our cohort. 19 patients (73%) had optimal outcomes and 7 (27%) had suboptimal but acceptable outcomes. Final in-stent gain in diameter at maximum stenotic area was 1.83±0.67mm. Out of 7 patients with sub-optimal (80-95%) stent expansion, 5 patients were found to have superficial calcific lesion. Similarly, out of 20 deep calcific lesions only 2 patients had sub-optimal stent expansion.

Conclusions:
IVL typically causes circumferential calcium fractures in several planes like circumferential, transmural planes, and thus seldom results in uniplanar "troughs" arising with atherectomy technologies due to guidewire bias. Procedural success achieved in 100% in our cohort. Superficial calcific lesions had strong association with sub-optimal stent expansion outcome (p: 0.000383). IVL is proving to be a valuable tool in dealing with coronary calcification.
Abstract 14153: The Effect of Gender on Atrial Fibrillation Ablation Outcomes Using a Propensity Score Matched Analysis
Authors: Gier Chad , Aslam Faisal , Al-Sadawi Mohammed , Ijaz Hina , Alsaiqali Mahmoud , Almasry Ibrahim , SINGH ABHIJEET , Rashba Eric J , Fan Roger
Published: June 2023

Introduction:
Previous studies have shown that woman with atrial fibrillation (AF) have increased non-pulmonary vein (PV) triggers which requires additional substrate modification during AF ablation. However, there remains an incomplete understanding of the impact of gender on AF ablation strategies and outcomes.

Methods:
At a single tertiary care center between January 2013 and July 2021, we analyzed 1576 AF ablations in 1412 patients, of whom 33% were female. Patients were followed for at least 6 months (mean 34 months) to detect AF recurrence, complications, and emergency room visits/hospitalizations. The effects of gender on AF clinical characteristics, AF recurrence, procedural approach and complications were assessed by multivariate logistic regression analysis using propensity score matching.

Results:
Of 1412 patients, mean age was 64 and mean BMI was 31 kg/m2. 77% underwent de novo ablations, and 27% patients had persistent AF at the time of ablation. The overall rate of AF recurrence was 37%. There was no difference in AF recurrence when stratified by gender (HR 1.15; CI: 0.92-1.43, p >0.05) and age (Fig. 1A & 1B). After propensity score matching gender 1:1 (criteria: age, type of AF, HTN, DM, and BMI, n = 888 patients), there was no difference in AF recurrence (Fig. 1C) or procedure related complications. Additional substrate modification was associated with persistent AF (OR 2.99; CI: 1.9-4.69, p <0.05) or age greater than 70 years (OR 1.03; CI: 1.02-1.05, p <0.05) with no difference based on gender. During ablation, first pass PV isolation was more likely achieved in males (OR 0.7; CI: 0.53-0.93, p <0.05) and patients with BMI < 30 kg/m2. There was no significant difference in the rate of PV reconnection during redo ablations between genders (OR 1.05; CI: 0.71-1.55, p >0.05).

Conclusions:
Despite a lower rate of first-pass PV isolation in female patients, there is no difference in overall safety or efficacy outcomes between genders following AF ablation.
Abstract 14156: Termination of Atrial Fibrillation During Ablation Predicts Long-Term Success
Authors: Vasilottos Nektarios , Kumar Awaneesh , McCoy Cody , Tanawuttiwat Tanyanan , Miller John M , Das Mithilesh
Published: June 2023

Background:
The predictive value of termination of atrial fibrillation (AF) during catheter ablation (CA) during a long-term follow-up is not known.

Methods:
We studied the predictive value of AF termination (spontaneous or induced) during ablation in patients who underwent CA of persistent and paroxysmal AF and followed them for recurrence of AF/atrial flutter (FL).

Results:
Of 187 patients (male: 75%, mean age: 60.3 ± 10.7 years) who underwent CA of AF, 65 (34.8%) patients had termination during the initial CA. A mean number of 1.4 ± 0.6 ablations were performed during follow-up in both groups. There were no significant differences in baseline characteristics including age, gender, race, body mass index, left ventricular ejection fraction, and presence of hypertension, diabetes, and valvular disease.

During a median (±1SE) follow-up of 5.23 ± 0.17 years, a significantly higher percentage of patients who had termination during CA were in sinus rhythm as compared to patients who did not have termination during CA (87.6 vs 63.1%, p < 0.001). Cox regression analysis confirmed termination of AF during ablation as a predictor of whether the patient was in sinus rhythm at time of last follow-up (OR: 0.24, 95% CI 0.09 to 0.62, p = 0.003). Kaplan-Meier survival analysis shows significantly decreased time to recurrence in patients who did not have AF termination than patients who had AF termination during CA.

Conclusion:
The present study identifies termination of AF during CA as a predictor of successful ablation during 5-year follow-up.
Abstract 14162: An Observational Study of Guideline-Directed Medical Therapy Optimization for Patients With Heart Failure With Reduced Ejection Fraction in Telehealth versus In-Person Visits
Authors: Shah Parth A , Almonte Matthew , Carter Spencer , Hulet Leiandie , Xac May , Hendren Nicholas , Amin Alpesh , Das Sandeep R
Published: June 2023

Introduction:
Rates of initiation and dose optimization of guideline-directed medical therapy (GDMT) for heart failure patients with reduced ejection fraction are suboptimal nationally. Recently, virtual medicine has been studied as a potential solution to help overcome barriers limiting GDMT optimization. We evaluated GDMT optimization during telehealth visits compared with in-person visits at Parkland Health, a large urban safety-net health system.

Methods:
Parkland has a registry of all patients with an ejection fraction
≤
40% on transthoracic echocardiography within the last three years. Using this registry data of patients seen in the Parkland cardiology clinic between September 2021 and February 2022, we compared GDMT prescriptions for patients before and after each clinic visit. We defined an optimization event as the initiation of a new class of GDMT, a switch to an angiotensin receptor/neprilysin inhibitor, or an increase in dosage of any class of GDMT. The rise of Omicron variant COVID-19 cases in Dallas led to a nearly universal shift of in-person to virtual visits in December 2021, allowing us to compare GDMT optimization rates between each visit type.

Results:
From 9/12/21 to 12/24/21, there were 147 visits of which 134 (91%) were in-person. Of these in-person visits, 58.2% led to an optimization event. From 12/25/21 to 2/12/22, there were 97 visits of which 84 (89%) were telehealth visits, all conducted by telephone. Of these telehealth visits, 16.1% led to an optimization event (p<0.001). Baseline characteristics of patients from each period were not significantly different (Table 1).

Conclusion:
Our study demonstrated GDMT optimization was significantly lower in telephone visits compared with in-person visits despite each group having similar demographics and medical co-morbidities. This observation should raise concern over increased reliance on telephone-only encounters, especially in urban resource limited populations.
Abstract 14174: Abnormal Exercise Electrocardiography With Normal Stress Echocardiography is Associated With Increased Subclinical Coronary Atherosclerosis: Insights From the Project Baseline Health Study
Authors: Duran Jessica M , Nguyen Maggie , Haddad Francois , Cauwenberghs Nicholas , Kuznetsova Tatiana , Bloomfield Gerald S , Mahaffey Kenneth , Hernandez Adrian F , Mega Jessica L , Short Sarah , Douglas Pamela S , Shah Svati H , Daubert Melissa A
Published: June 2023

Introduction
Patients with an abnormal (positive) exercise electrocardiography (ECG), but normal stress echocardiography (+ECG/-Echo) have more adverse cardiac events than patients with a negative ECG and normal stress Echo (-ECG/-Echo). However, it is unclear if ECG/Echo discordance is associated with a greater burden of concurrent subclinical coronary atherosclerosis.

Methods
In the Project Baseline Health Study (PBHS), participants underwent stress Echo and a coronary artery calcium (CAC) scan. For this PBHS substudy, participants with no known coronary artery disease (CAD) were analyzed by stress result: -ECG/-Echo, +ECG/-Echo, or +Echo (with or without +ECG). Patients with a submaximal stress test, uninterpretable ECG, resting wall motion abnormality, and/or baseline ejection fraction <50% were excluded. Clinical characteristics, exercise performance, and CAC results were compared between the -ECG/-Echo and +ECG/-Echo groups using the chi-squared test and Student’s t-test for categorical and continuous variables, respectively. ANOVA or Kruskal-Wallis test was used, as appropriate, to compare all 3 groups.

Results
Among 1466 participants, 1357 (92.6%) had a -ECG/-Echo; 85 (5.8%) had a +ECG/-Echo; and 24 (1.6%) had a +Echo. Compared to the -ECG/-Echo group, participants in the +ECG/-Echo group were older with shorter exercise duration, but younger with fewer risk factors than participants with a +Echo. The median 10-year ASCVD risk score was 2% for -ECG/-Echo, 3% for +ECG/-Echo, and 10% for +Echo (p<0.001). Greater abnormalities by exercise stress Echo were associated with an increased burden of concurrent coronary atherosclerosis as assessed by CAC score and CAC volume (Table).

Conclusions
Individuals with positive exercise ECG, even with normal stress Echo, have a higher burden of subclinical coronary atherosclerosis than those with -ECG/-Echo, which may explain the increased risk for adverse cardiac events in the +ECG/-Echo population.
Abstract 14177: Utilization of Optimal Guideline-Directed Medical Therapies Among Patients Newly-Diagnosed With Heart Failure and Reduced Ejection Fraction: An Analysis From the Optum Database (2016-2020)
Authors: Sumarsono Andrew , Xie Luyu , Zhang Chenguang , Greene Stephen J , Fonarow Gregg C , Thibodeau Jennifer T , Farr MaryJane , Khan Mohammad S , Butler Javed , Morris Alanna A , Vaduganathan Muthiah , Messiah Sarah , Pandey Ambarish
Published: June 2023

Introduction:
Optimal guideline-directed medical therapies (GDMT) improves clinical outcomes among patients with new-onset HFrEF. Limited data exist on achievement of optimal GDMT in the first 12 months among newly diagnosed patients with HFrEF.

Methods:
2016-2020 OPTUM Claims Database, which includes privately insured and Medicare patients covered through the United Healthcare insurance, was used. Patients with new-onset HF were identified using validated ICD-10 codes and a 12-month look back to exclude prevalent HF. HFrEF patients were identified based on claims with ICD-10 codes of I50.2 and I50.4 within 6 months of HF diagnosis. Rates of optimal GDMT (≥50% target dose of ACEI or ARB or any dose of ARNI, ≥50% dose of beta-blocker, and any MRA) within 12 months of the incident HF diagnosis were compared overall and across race- and sex- groups. Adjusted Cox-proportional hazards models were used to evaluate the association of different patient-level factors with time to optimal GDMT during 12-month follow-up.

Results:
The study included 118963 patients with new-onset HFrEF (Age: 72 years, 15.8% Black, 57.4% Men). Only 8.3% achieved optimal GDMT during the 12 months after incident HF diagnosis. The optimal GDMT use within 12-months of HF diagnosis was low across the race-ethnic and gender groups (
Figure 1A/1B
). In adjusted Cox models, younger age, Black race, male sex, prevalent HF risk factors including hypertension, private (vs. Medicare insurance), and interval hospitalizations during the follow-up period were each associated with increased probability of achieving optimal GDMT (
Figure 1C
). In contrast, prevalent COPD, stroke/TIA, and polypharmacy were associated with a lower probability of achieving optimal GDMT.

Conclusions:
Utilization of optimal GDMT among patients with HFrEF is very low in the first 12 months after diagnosis. These findings highlight the need for aggressive implementation strategies to optimize GDMT utilization after new HF diagnosis.
Abstract 14179: Unsupervised Machine Learning on Myocardial Deformation Curves Identifies Specific Clusters of People at Risk of Heart Failure - The Copenhagen City Heart Study
Authors: Simonsen Jakob Oeystein , Modin Daniel , Skaarup Kristoffer G , Djernæs Kasper , Lassen Mats , Johansen Niklas D , Sanchez Sergio , Claggett Brian , Marott Jacob , Thorsten Magnus , Jensen Gorm , Schnohr Peter , Mogelvang Rasmus , Biering-Srensen Tor
Published: June 2023

Background
Peak global longitudinal strain is recognized as a powerful predictor of heart failure (HF). However, whether the entire strain curve add important prognostic information regarding risk of HF remains unknown. We aimed to investigate whether patterns of myocardial deformation identified through unsupervised machine learning (uML) entailed additional information regarding risk of HF.

Methods
Longitudinal strain curves from 3,710 subjects from the general population without prevalent HF were clustered by similarity using uML based on strain curves alone. The grouped clusters were then compared by incidence rate of HF and in multivariable COX models.

Results
Mean age was 56 years and 43% were male. During a median follow-up of 5.3 years, 92 subjects (2.5%) developed HF. The uML algorithm generated a hierarchical clustering tree (Figure 1) and 10 different clusters. Generally, with increasing incidence of HF, strain curves displayed a smaller reduction of strain from peak-GLS to the maximal curvature during the early filling relative to the size of their peak-GLS (Figure 1 and 2): We called this value early diastolic strain to peak-GLS (EDS to peak-GLS). One exception was cluster 9. In multivariable Cox regression, cluster 9 was significantly associated with increased incidence of HF when compared to cluster 3,4 and 5 [For cluster 3: HR 6.6, 95%CI: 1.5;29.0, p = 0.013] even though the subjects of cluster 9 were younger (40 years), displayed healthier clinical baseline characteristics, and only had slightly reduced Peak-GLS. The mean strain curve of the lateral basal segment of cluster 9 displayed an early systolic lengthening followed by a late and reduced contraction specifically related to the basal lateral segment (Figure 3).

Conclusion
uML could identify clusters with high incidence of HF based on strain curves alone. The algorithm identified unknown strain patterns beyond peak-GLS presumably related to increased risk of HF.
Abstract 14184: Outcomes of Transcatheter Aortic Valve Implantation in Patients With Severe Morbid Obesity
Authors: Ullah Waqas , Halboni Adnan , Alhusain Rashid , Zghouzi Mohamed , Roomi Sohaib S , sattar yasar , Alraies M C
Published: June 2023

Introduction:
The long-term effects of severe obesity [body mass index (BMI) ≥50 kg/m
2
) on the outcomes of Transcatheter Aortic Valve implantation (TAVI) remains unknown.

Methods:
The National Readmission Database (NRD) was used from 2015-2019 to identify all patients undergoing TAVI. Patients with severe obesity were compared with those having BMI <50 kg/m
2
. The adjusted odds ratios (aOR) and 95% confidence interval (CI) were calculated using a propensity-score matched analysis (PSM).(Fig 1)

Results:
A total of 184,199 patients were included in the crude analysis. A selected sample of 4669 [2369 (50.7%) severely obese, and non-obese 2300 (49.3%)] were included in PSM analysis. At index admission, the adjusted odds of net adverse clinical events (NACE) (aOR 1.57, 95% CI 1.12 -2.20, p=0.01), all-cause in-hospital mortality (aOR 8.08, 95% CI 3.19-20.48, p=<0.0001), and acute kidney injury were (aOR 1.48, 95% CI 1.25-1.74, p=<0.0001) were significantly higher in severely obese patients compared with those having with BMI<50 kg/m
2
. There was no difference in stroke (aOR 0.60, 95% CI 0.32-1.11, p=0.14), or major bleeding (aOR 1.63, 1.01-2.64, p=0.06) between the two groups. At 30- and 180-day, there was no significant difference in the incidence of stroke, or major bleeding between the two groups.(Fig 2) There was a steep increase in the utilization of TAVI in severely obese patients from 17.6% to 31.8% per total procedures during 2016 to 2019.

Conclusions:
Severely obese (BMI ≥50 kg/m
2)
recipients of TAVI have a higher risk of NACE and mortality, however, there appearsto be no significant difference in the long-term risk of complications between severely obese and non-obese patients.
Abstract 14210: Heart Failure Hospitalizations and Mortality Outcomes in PV142I Transthyretin Cardiomyopathy Patients Treated With Tafamidis
Authors: Patel Rahul , Steinberg Rebecca , Rim Austin , Brown Matthew T , Yalamanchili Sreeram , Rangaswamy Nandakumar Dhanish Revanth , Bhatt Kunal
Published: June 2023

Introduction:
TTR amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure in the geriatric population. The pV142I (V122I) transthyretin gene mutation is carried in 3.4% of African Americans. It is the most common cause of hereditary ATTR-CM (hATTR-CM) in the United States with a median survival of 2.5 years from diagnosis. Tafamidis is a selective transthyretin stabilizer approved in 2019 that has been shown to improve survival in wild type and hereditary ATTR-CM with New York Heart Association class I to III symptoms. The impact of tafamidis treatment on heart failure hospitalization (HFH) and mortality outcomes in pV142I hATTR-CM requires further investigation.

Hypothesis:
Tafamidis decreases HFH and mortality in pV142I ATTR-CM.

Methods:
We conducted a retrospective chart review of patients diagnosed with ATTR-CM with pV142I mutations enrolled in Emory University's Cardiac Amyloidosis Clinic between January 2014 and February 2022. Kaplan-Meier (KM) curves stratified by tafamidis use were generated for mortality and first HFH within 2 years of initial diagnosis. Log-rank test was used to compare KM curves. A p-value < 0.05 was considered significant.

Results:
111 patients in our study have pV142I hATTR-CM, including 47 (42%) prescribed tafamidis and 64 (58%) who were not prescribed. The median survival was 616 [interquartile range 277-731] days for patients treated with tafamidis and 595 [216, 731] days for untreated patients. The median time to HFH with tafamidis was 464 [167, 685] days and 233 [41, 613] days for untreated patients. Patients with tafamidis use had both lower rate of mortality (p = 0.005) and HFH (p = 0.035) than those who did not.

Conclusion:
In patients with pV142I hATTR-CM within our cohort, tafamidis use was associated with lower rates of mortality and heart failure hospitalization. These findings are consistent with previously described benefits in a generalized ATTR-CM population.
Abstract 14225: Atrial Tachycardias After Surgical Left Atrial Appendage Exclusion
Authors: Rich Lucas , Deshmukh Amrish , Cunnane Ryan , Latchamsetty Rakesh , Crawford Thomas , Chugh Aman , Morady Fred , Romano Matthew A , Oral Hakan
Published: June 2023

Introduction:
Surgical left atrial appendage exclusion (LAA-Ex) is often performed to eliminate the need for long-term anticoagulation either as a stand-alone or concomitant procedure during cardiac surgery. A modified MAZE procedure is also usually performed during surgical LAA-Ex. Residual arrhythmogenic foci within the LAAA and/or zones of slow conduction along the stump of the LAA may contribute to recurrent atrial tachycardias (AT) after LAA-Ex. The purpose of this study was to determine the role of the LAA in recurrent atrial tachycardias (ATs) after surgical LAA-Ex.

Methods:
Catheter ablation (CA) was performed to eliminate ATs in 21 patients with history of AF (persistent in 18/21, 86%) 25±26 months after surgical LAA-Ex. There were 3 women; mean age was 66±9 years; and the left atrial diameter was 54±8 mms. A concomitant MAZE procedure and CA was performed previously, in 16 and 9 patients, respectively. Two patients had neither maze nor catheter ablation. There was residual blood flow into the LAA in 1/21 patient.

Results:
A reentrant AT involving the stump of the LAA was identified in 5/21 (24%) patients. Focal ablation on a critical isthmus within a zone of slow conduction along the LAA stump terminated AT in 3/5 patients. In the remaining 2 patients a linear lesion set from the stump to an existing line of block (left atrial roof line and anterior mitral annulus) terminated the macroreentrant AT revolving around the LAA stump. During 16±13 months of follow-up 10/21 patients (48%) remained free from recurrent ATs without antiarrhythmic drug therapy. A repeat ablation was performed in 3 patients, the mechanism of the AT was epicardial, perimitral, and multifocal but did not involve the LAA.

Conclusions:
After surgical LAA-Ex recurrent ATs are not uncommon and can involve the LAA stump, Although these ATs can be successfully identified and ablated, other ATs may recur and prompt additional antiarrhythmic or ablative therapy.
Abstract 14235: Hepatocyte Tissue Plasminogen Activator Limits Very-Low-Density Lipoprotein Production via Inhibiting ApoB-Microsomal Transfer Protein Interaction and ApoB Lipidation
Authors: Dai Wen , zhang heng , Lund Hayley , Kuriakose George , Zhang Ziyu , Rodriguez Maya , Zhu Jieqing , Sorci Thomas Mary , Silverstein Roy , Ginsberg Henry , Sahoo Daisy , Tabas Ira , Zheng Ze
Published: June 2023

Lower plasma tissue plasminogen activator (tPA), a key fibrinolytic enzyme, is associated with higher atherogenic cholesterol levels in humans, but the mechanism is unknown. Hepatocyte (HC) is the factory producing atherogenic apoB lipoproteins, also a major source of basal plasma tPA. Our hypothesis is that tPA limits apoB-VLDL production in HCs.Silencing tPA in HCs using AAV8-H1-sh-tPA in

Ldlr
-/-

mice leads to increased plasma cholesterol, triglyceride, apoB, and exacerbated atherosclerosis compared with scramble-silenced controls. Fractionation of plasma lipoproteins by FPLC or ultracentrifugation shows increased cholesterol and apoB in VLDL and LDL fractions. Inhibiting VLDL hydrolysis by P407 leads to a faster plasma triglyceride-rising rate in HC-tPA-silenced wild type mice, suggesting higher hepatic VLDL production. In a pulse-chase assay, tPA-silenced human primary HC has higher apoB-associated radioactivity in cell medium and lysate, suggesting increased apoB production.Adequate apoB lipidation is required for its secretion. By electronic microscopy, the distribution of VLDL shifts to a larger diameter in plasma VLDL isolated from HC-tPA-silenced

Ldlr
-/-

mice, suggesting higher lipid contents in VLDL. The endoplasmic reticulum (ER)-associated apoB is higher in tPA-silenced vs. control HCs, more prominent in the less denser density fractions. As density and lipidation are inversely related, these findings are consistent with the hypothesis that tPA limits apoB lipidation in ER. MTP is an ER chaperone incorporating neutral lipids onto apoB in HC. The tPA-silenced human primary HC has higher neutral lipid transfer activity than controls, despite similar MTP protein levels. Moreover, higher apoB is in the anti-MTP-precipitations from tPA-silenced vs. control HCs, suggesting that silencing tPA increases apoB-MTP interaction. Proximity ligation and immunoprecipitation assays show tPA interacts with apoB in HC. Solid-phase binding assay and native gel reveal purified human tPA binds to LDL, but not to MTP. tPA competes with MTP in binding to LDL. Moreover, tPA inhibits MTP-mediated neutral lipid transfer. These findings suggested tPA binds to apoB and inhibits MTP-dependent apoB lipidation and VLDL secretion.
Abstract 14239: Development and Validation of a Daily Measure of Cardiorespiratory Fitness - Estimated Vo
2
Max - Using Multiparametric Data From a Wearable Sensor
Authors: Richards Dylan M , Gendy Maged , Larimer Karen A , Steinhubl Steven R , Pipke Matthew
Published: June 2023

Introduction:
The objective determination of a person’s cardiorespiratory fitness over time, especially in those with heart failure, can play a critical role in optimizing individual therapies, identifying early signs of decompensation, and accelerate the development of novel therapeutic interventions. However, existing methods, such as formal cardiopulmonary exercise testing (CPET), or surrogates like a 6-minute walk test (6MWT) are difficult for both patients and health systems and provide only sparse samples.

Hypothesis:
Using a wearable ECG-patch sensor and machine learning methods, cardiorespiratory fitness can be estimated daily using routine vital sign dynamics during free-living activities.

Methods:
CPETs and multiple days of ECG-patch sensor data were collected within 2 weeks of each other for 228 participants (146 normal, and 82 with Heart Failure). A model for VO
2
max estimation was developed using a two-stage procedure. (Figure) In the first stage, the model was pretrained on an unsupervised regression task on over 2000 unique patients’ data, representing over 200 patient-years of activity of daily living. The second stage fine-tuned the pretrained model to predict VO
2
max, using a K-Fold cross validation procedure with 50% train, 25% validation, and 25% testing for four folds.

Results:
CPET-determined VO
2
max values ranged from 7.1 to 69.1 ml/kg/min (median=28.9, IQR=24.5). The Pearson Correlation Coefficient (PCC) and Mean Absolute Error (MAE) of the estimated VO
2
max was 0.85 and 6.2 ml/kg/min, respectively. For the heart failure subgroup, the PCC and MAE are 0.73 and 3.7 ml/kg/min, respectively. (Figure)

Conclusion:
Our results show that estimated VO
2
max can be accurately and conveniently determined at high frequency in individuals with a wide range of cardiorespiratory fitness using data from a patch sensor during routine daily activities. Ongoing work in a large HF trial will evaluate its performance over time relative to 6MWT and surveys.