bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14874: Electrical Isolation of the Posterior Left Atrium is Associated With a Lower Incidence of Atrial Tachycardia in Patients With Persistent Atrial Fibrillation
Authors: Chou Andrew , Jongnarangsin Krit , Yokokawa Miki , Ghannam Michael , Liang Jackson , Oral Hakan , Morady Fred , Chugh Aman
Published: June 2023

Introduction:
Patients may develop atrial tachycardia (AT) after left atrial (LA) ablation of persistent atrial fibrillation (AF).

Hypothesis:
We hypothesized that patients with persistent AF undergoing electrical isolation of the posterior wall of the LA would be less likely to experience AT, and specifically, roof-dependent tachycardia as compared to historical controls who only received linear ablation at the LA roof.

Methods:
The population consisted of 101 consecutive patients (age= 64.3±8.7 years, 70 males (69%), LA=4.6±0.8 cm, ejection fraction=48.5±16%) undergoing their initial procedure for persistent AF. After pulmonary vein isolation, patients either underwent posterior LA isolation (n=50; study group) or linear ablation at the LA roof with verification of conduction block by established pacing maneuvers (n=51; control group)

Results:
During the initial procedure for AF, electrical isolation of the posterior LA or linear block at the LA roof were achieved in all patients in the study or control groups, respectively. During follow-up, patients in the study group were less likely to develop AT (9/50 [18%] vs. 18/51 [35%]; p=0.02), roof-dependent (1/50 [2%] vs. 8/51 [16%]; p=0.008), and multi-loop AT (6/50 [12%] vs. 14/51 [27%]; p=0.03) as compared to controls. A repeat procedure was performed in 18 (34%) and 28 (55%) patients in the study and control groups, respectively (p=0.03). After a mean follow-up of 25.3 ± 13, and 50.3 ± 27.3 months, 45 of the 50 study (90%), and 44 of the 51 control patients (86%) remained in sinus rhythm (p=0.72), with 12 and 13 patients taking antiarrhythmic medications, respectively (p=0.43)

Conclusions:
In patients with persistent AF, posterior LA isolation is associated with a lower risk of a redo procedure, roof-dependent macro-reentry, and post-ablation AT in general as compared to controls who only received linear ablation of the left atrial roof. Posterior LA isolation also obviates pacing maneuvers, the results of which might be equivocal, and may be a more definitive endpoint of linear ablation at the LA roof
Abstract 14891: Sudden Cardiac Arrest Manifesting With Pulseless Electrical Activity: Is There A “Sweet Spot” for Survival?
Authors: Holmstrom Lauri , Chugh Harpriya , Salmasi Shiva , Uy-Evanado Audrey , Sorenson Chad , Bhanji Ziana , Seifer Madison , Sargsyan Arayik S , Young Christopher , Hurst Sean , Salvucci Angelo , Jui Jonathan , Reinier Kyndaron , Chugh Sumeet S
Published: June 2023

Introduction:
The proportion of sudden cardiac arrests (SCA) manifesting with pulseless electrical activity (PEA) has increased significantly, and survival rate remains poor. However, a small PEA-SCA subgroup does survive and may yield key predictors of improved outcomes when compared to non-survivors.

Aim:
To identify clinical and resuscitation factors that predict survival from PEA-SCA.

Methods:
Our study sample is drawn from two ongoing community-based, prospective studies of out-of-hospital SCA. The Portland, OR metro area (Pop. approx. 1 million; 2002-2017) was used as a discovery population and Ventura County CA (Pop. approx. 850,000, 2015-2021) was the validation population. For the present sub-study, we included SCA cases with PEA as the presenting rhythm, who were resuscitated by EMS personnel.

Results:
In Oregon SUDS, we identified 1,057 PEA-SCA cases of which 105 (10%) survived to hospital discharge (STHD). The mean age of PEA cases was 68.4±15.8 years and 62% were male. In a multivariable model including resuscitation variables (age, sex, witnessed SCA, EMS response time, bystander CPR, public location), age (OR 0.98, 95% CI 0.97-0.99; p=0.001), male sex (OR 0.58, 95% CI 0.38-0.88; p=0.01), witnessed SCA (OR 3.0, 95% CI 1.7-5.3; p<0001), and public location (OR 1.9, 95% CI 1.1-3.1; p=0.01) associated with STHD. In a multivariable model including clinical variables (age, sex, BMI, CAD, HF, CKD, DM, COPD, asthma), only age (OR 0.97, 95% CI 0.95-0.99; p=0.003) had an association with STHD. In Ventura PRESTO, we identified 695 PEA-SCA cases of which 82 (12%) were STHD. The mean age of PEA cases was 73.1±15.6 years and 63% were male. In a multivariable model including the same resuscitation variables, age (OR 0.97, 95% CI 0.95-0.98; p<0.001) and public location (OR 3.6, 95% CI 1.7-7.6; p=0.001) associated with STHD. In a multivariable model including the same clinical characteristics, we found no significant predictors of STHD.

Conclusions:
Young age and cardiac arrest in a public location were the only independent predictors of survival from PEA-SCA in both discovery and validation populations. These findings suggest that enhancement of the community response to cardiac arrest may have the potential to improve survival outcomes in PEA-SCA.
Abstract 14894: Mst1 Mediates Doxorubicin-Induced Cardiomyopathy by Sirt3 Downregulation
Authors: Schirone Leonardo , Vecchio Daniele , Forte Maurizio , Schiavon Sonia , D'Ambrosio Luca , Sciarretta Sebastiano
Published: June 2023

INTRODUCTION:

Heart failure is a major side effect of doxorubicin (DOX) treatment in patients with cancer. However, the mechanisms underlying the development of DOX-induced cardiomyopathy (DCM) need to be addressed. Here, we demonstrate that the serine/threonine kinase MST1, a major component of the Hippo pathway, contributes to the development of DOX-induced myocardial injury.

HYPOTHESIS:

The inhibition of MST1 protects from DCM by preserving SIRT3 expression

METHODS:

C57BL/6J WT mice and mice with cardiomyocyte-specific dominant-negative MST1 (kinase-dead, DN-MST1) overexpression received 3 weekly injections of DOX, reaching a final cumulative dose of 18 mg/kg. Echocardiographic, histological and biochemical analyses were performed 6 weeks after the first administration of DOX.

RESULTS:

MST1 signaling was significantly activated in cardiomyocytes in response to DOX treatment in vitro and in vivo. Wild-type (WT) mice treated with DOX had reduced fractional shortening (46,1±1,8 vs. 31,1±1,1, n=7-11, p<0.0001) and TEM mitochondrial abnormalities (3,7±0,9 vs. 10,2±1,5, n=12, p<0.0001). However, systolic dysfunction was abolished in mice with CM-specific overexpression of DN-MST1 (31,1±1,1 vs. 46,3±1,1, n=11, p>0.0001) or treated with the MST1 inhibitor ‘XMU-MP-1’ (37,5±1,8 vs. 46,6±1,9, n=8, p<0.01), indicating that MST1 inhibition attenuates DOX-induced cardiac dysfunction. DOX treatment also led to a significant downregulation of cardiac levels of SIRT3 (1±0,1 vs. 0,6±0,1, p<0.05), a deacetylase involved in mitochondrial protection, in WT mice, which was rescued by MST1 inhibition (0,6±0,1 vs. 1,3±0,04, p<0.001). Pharmacological inhibition of SIRT3 blunted the protective effects of MST1 inhibition (44,5±1,6 vs. 32,5±2,3, n=4, p<0.01), indicating that SIRT3 downregulation mediates the cytotoxic effects of MST1 activation in response to DOX treatment. Finally, we found a significant upregulation of MST1 levels in human myocardial tissue of cancer patients treated with DOX (1,5±0,23 vs. 2,4±0,12, N=81-123 cells from 3 different patients, p<0.001).

CONCLUSION:

MST1 contributes to DOX-induced cardiomyopathy by promoting mitochondrial damage through SIRT3 downregulation in cardiomyocytes.
Abstract 14904: Post-Tavr 30-Day and 90-Day Readmission for Acute Coronary Syndrome - Insight From the National Readmission Database
Authors: Ebner Bertrand , Martillo Miguel , Inestroza Karla , Kaur Sukhpreet , Ergui Ian , Albosta michael , Vergara-Sanchez Carlos , Hernandez Rafael J , Dangl Michael , Grant Jelani , VINCENT LOUIS , Maning Jennifer , Olarte Neal , Colombo Rosario
Published: June 2023

Background:
Post-transcatheter aortic valve replacement readmissions are increasingly the major focus of quality improvement efforts. Limited data exist about patient post-TAVR readmitted for acute coronary syndrome (ACS).

Methods:
The National Readmission Sample was queried from 2011-2017 for relevant ICD-9 and ICD-10 codes to identify patients who underwent TAVR who presented with ACS as primary diagnosis after indexed admission for TAVR. We identified 30-day and 90-day readmission rate, characteristics, mortality and in-hospital outcomes.

Results:
A total of 104,920 patients underwent TAVR. We identified 623 (0.6%) patients with primary diagnosis of ACS post-TAVR. From the patients who presented with ACS, 31% (n=193) and 41% (n=256) occurred within 30 days and 90 days of TAVR, respectively. Within 30-day and 90-day readmission for ACS post-TAVR, average age was 80.2 years and 80.3 years with 66.7% and 61.1% being male, respectively. Baseline characteristics are highlighted on Table 1. Mortality in patients post-TAVR who were readmitted in 30 days and 90 days for ACS was 14.8% and 9.3%, respectively.

Conclusions:
Although readmissions after TAVR in patients with ACS is relatively low (0.6%), they are associated with higher in-hospital mortality rate than the general population who present with ACS (~7 to 8%) and pose a higher health care burden.
Abstract 14906: Impact of Time Between Stacked Lesions During Radiofrequency Atrial Ablation With Active Esophageal Cooling
Authors: Mercado Montoya Marcela , Gomez-Bustamante Tatiana , Berjano Enrique , Kulstad Erik B , Mickelsen Steven R , Hernandez-Arango Pablo , Schieber Jay , Daniels James D
Published: June 2023

Background:
Active esophageal cooling during radiofrequency (RF) ablation of the left atrium (LA) has been shown to reduce esophageal injury. Although no atrioesophageal fistula has been reported in over 12 thousand uses to date, the first pericardio-esophageal fistula to occur despite cooling reinforces the fact that a threshold may exist at which heat extraction capacity may be surpassed. We aimed to examine this threshold by measuring the transmurality of esophageal injury after sequential lesion placement.

Hypothesis:
Reduced rest time between stacked lesions increases tissue lesion depth by enhancing thermal latency effects.

Methods:
Using a computational model of the left atrium, we determined esophageal lesion depth between sequentially placed RF lesions using high-power, short duration power settings (50 W for 10 s). Lesion depth was determined via Arrhenius equation, and anatomical dimensions were:1.5 mm for atrial myocardium, 0.75 mm for pericardial tissue, and 2 mm for the esophagus. Three lesions were placed on the myocardium with either 5 s or 10 s pauses in between. Final lesion transmurality was measured 45 s after the last placement to fully account for latent heating.

Results:
Active esophageal cooling reduced esophageal lesion transmurality by 80% after the first lesion. Sequential lesions increased esophageal lesion transmurality, with thermal latency contributing to increased lesion depth even after cessation of RF energy. Shorter timing between lesions allowed further growth in transmurality: 4% for 90 W, and 8.5% for 50 W power settings (Figure 1), showing that the efficacy of cooling against thermal latency effects decreased with the placement of each subsequent lesion.

Conclusions:
Active esophageal cooling reduces esophageal lesion transmurality by 80% when single lesions are placed. Stacking additional lesions at the same point reduces this safety benefit, with shorter intervals between lesions resulting in less protective effect.
Abstract 14915: Efficacy of Canagliflozin on Heart Failure Hospitalization Across Diabetes-Specific Risk Scores
Authors: Segar Matthew W , Khan Mohammad S , Patel Kershaw , Vaduganathan Muthiah , Verma Subodh , Butler Javed , Tang Wai Hong W , Pandey Ambarish
Published: June 2023

Introduction:
Canagliflozin (CAN) vs. placebo (PBO) reduced the risk of hospitalization for heart failure (HHF) in type 2 diabetes. Whether this benefit is uniform across diabetes-specific HF risk scores (WATCH-DM and TRS-HF
DM
) is not known.

Methods:
Using data from the pooled CANVAS and CANVAS-R trials, we stratified participants without prevalent HF by the integer WATCH-DM score derived quintiles (low [≤14] = quintiles 1-2, intermediate [15-19] = quintiles 3-4, high [≥20] = quintile 5) and by the TRS-HF
DM
score (low [0-1], intermediate [2], high [3-6]). Discrimination and calibration were assessed by Harrell’s C-index and Hosmer-Lemeshow test, respectively. Cox regression models evaluated the effect of CAN on risk of HHF across risk score categories.

Results:
Among participants without prevalent HF (n = 8,691), CAN vs. PBO reduced the risk of HHF (HR 0.80, 95% CI 0.62-1.03). The WATCH-DM score demonstrated a C-index of 0.70 (95% CI, 0.66-0.73) and no evidence of miscalibration (χ
2
< 20). CAN consistently reduced risk of HHF across WATCH-DM strata (P-intxn = 0.55) with the greatest absolute risk reduction and lowest NNT observed in the highest vs. lowest risk cohort (ARR 4.6% vs. 0.3% and NNT 22 vs. 333) (
Fig. A
). Comparatively, the TRS-HF
DM
demonstrated a C-index of 0.67 (95% CI, 0.63-0.71) and no evidence of miscalibration (χ
2
< 20). Similar to WATCH-DM, patients in the highest TRS-HF
DM
risk group derived the greatest absolute risk reduction and lowest NNT (ARR 3.1% vs. -0.3%% and NNT 32 vs. -333) with no differences across strata (P-intxn = 0.17) (
Fig. B
).

Conclusions:
Both the WATCH-DM and TRS-HF
DM
can accurately stratify HHF risk in patients with type 2 diabetes and free of HF. Greater absolute risk reductions with CAN vs PBO were observed with higher risk scores.
Abstract 14936: Profiling of Microrna Expression in Extracellular Vesicles Released From Ischemic Skeletal Muscles in Hypercholesterolemic Conditions
Authors: Dussault Sylvie , Raguema Nozha , Luo Yi Hui , Desjarlais Michel , Rivard Alain
Published: June 2023

Introduction:
Hypercholesterolemia (HC) is an important cardiovascular risk factor associated with impaired neovascularization in response to ischemia. We found that specific microRNAs (miRs) whose levels are reduced in ischemic skeletal muscles of mice exposed to HC can rescue endothelial cell function and neovascularization. miRs can be transferred between cells via extracellular vesicles (EVs). EVs are involved in several biological functions including the response to ischemia and angiogenesis.

Hypothesis:
Here we tested the hypothesis that HC causes alterations in the miR content of EVs related to ischemia/neovascularization.

Methods:
We used a mouse model of peripheral artery disease to induce severe ischemia in the hindlimbs of hypercholesterolemic ApoE
-/-
and control C57Bl/6J mice. Microvesicles (MVs) and exosomes (exo) were isolated from ischemic skeletal muscles by differential centrifugation. Total RNA was extracted from these 2 types of EVs, and the miR content was analyzed using next generation sequencing.

Results:
Bioinformatic analysis of the 100 most expressed miRs in EVs showed an enrichment of 38 miRs in MVs compared to ischemic skeletal muscles, and an enrichment of 44 miRs in exo compared to ischemic skeletal muscles. Among enriched miRs, 27 are common to both MVs and exo. We identified specific miRs enriched in EVs that are known to modulate angiogenesis, including several miRs that were altered by HC. For example, among enriched miRs downregulated by HC in EVs, the let-7 family and miR-29a are known to be pro-angiogenic via inhibition of members of the TIMP family. On the other hand, among enriched miRs upregulated by HC in EVs, miR-199a and miR-16-5p are known to be anti-angiogenic via inhibition of VEGF.

Conclusions:
This study describes for the first time the effect of HC on the modulation of miR profile in EVs following skeletal muscle ischemia. We found that several angiogenesis-modulating miRs are enriched in EVs and altered by HC. Our findings constitute a solid framework for the identification of miRs that could be targeted to modify EV content in atherosclerotic conditions. Eventually these engineered EVs could serve as vectors to promote neovascularization and reduce ischemic damages in severe vascular diseases.
Abstract 14942: Neurovascular Injury in a Mini-Swine Model of Recanalized Acute Ischemic Stroke
Authors: Bobi Joaquim , Taha Aladdin , Volovici Victor , Raben Jadey D , van Noort Romy , Stam Mathijs , Duncker Dirk J , Dammers Ruben , Dippel Diederik W , Van Beusekom Heleen M
Published: June 2023

Background, hypothesis:
Gyrencephalic large-animal models of acute ischemic stroke (AIS) such as swine gain attention in translating preclinical to clinical stroke research, with brain anatomy similar to humans. Most swine models employ young animals with AIS by permanent occlusion (P-AIS). This does not reflect the, often elderly, stroke patient. Therefore, recanalized AIS (R-AIS) in adult mini-pigs could improve preclinical to clinical translation.

Methods:
Anesthetized adult (2 yrs) Aachen mini-pigs (n=6) underwent craniotomy to occlude right-side middle cerebral arteries (MCA) with aneurysm clips. Clips were released at 4 hrs to allow recanalization for 2-4 hrs (R-AIS, n=4) or left in place until sacrifice (P-AIS, n=1). 3D angiography confirmed occlusion and recanalization. Infarct size was determined by TTC staining and expressed as % infarct per hemisphere (median, min-max). Qualitative neurovascular histology was performed in HE-stained sections of ischemic and remote (contralateral) tissue.

Results:
All animals survived until end-of-procedure. In 4 of 5 animals R-AIS successfully induced cortical infarcts (infarct size, 16.2% [9.1%-25.2%]). R-AIS was unsuccessful in 1 animal, with a small
striatum
infarct (2.7%) without cortical involvement and unclear angiographic occlusion. P-AIS (n=1) resulted in 12.7% infarct. Assessment of ischemic (TTC-neg) tissue revealed characteristic histology of ischemia/reperfusion-derived neurovascular damage, including erythrocyte extravasation, vasostasis, increased perivascular space and intravascular platelet/fibrin aggregates (
Figure 1
) in all animals. Remote tissue did not show any of these features.

Conclusions:
Adult Aachen mini-pigs can be used for acute ischemic stroke modelling and display characteristic neurovascular features associated with ischemia and reperfusion. They may serve as a model for translational therapeutic neuro(vascular)-protective research.
Abstract 14955: The Biological Bases of Psychosocial Stress-Associated Cardiovascular Disease: Investigating the Cardioprotective Properties of Central Arginine-Vasopressin
Authors: Gil Mario , Dominguez Fernando , Alaniz Esperanza I , Chalons Alexandra , VandeBerg John L
Published: June 2023

Psychosocial stressors (e.g., anxiety, personality traits, social isolation) are risk factors for cardiovascular events and heart disease. However, there is a lack of knowledge regarding the biological mechanisms that underlie this risk-outcome relationship. To address this knowledge gap, our team uses two non-traditional animal models, the Syrian hamster (
Mesocricetus auratus
) and gray short-tailed opossum (
Monodelphis domestica
). We previously reported that social isolation-induced aggression, a type of psychosocial stress experience, leads to increased neural activation in the ventral tegmental area (VTA) of the midbrain. The VTA contains tyrosine hydroxylase (TH)-producing (putative dopamine, DA) neurons and is innervated by vasopressin (AVP) fibers. DA and AVP play a role in social behavior, and we investigated whether these two systems interact when an individual experiences psychosocial stress-induced aggression. Here we report that social interactions increased Fos, the protein product of the immediate early gene
c-fos
that serves as a marker of neuronal activation, in non-TH cells in an area of the VTA called the interfascicular nucleus (IF) of male subjects. Previous social experience increased the number of TH-positive cells in the IF but had no effect on the number of AVP-ir fibers. Conversely, levels of aggressive and social dominance behaviors were positively correlated with the number of AVP-ir fibers in the IF, whereas there was no relationship between these behaviors and the number of TH-positive cells. In socially naïve males, AVP microinjected into the VTA inhibited the duration of aggressive behavior. We are currently investigating the impact of our psychosocial stress paradigms on myocardial injury in both males and females. Our results suggest a complex interaction between AVP and DA systems in the brain in psychosocial stress responses. Our long-term goal is to build on these preliminary findings to determine whether AVP in the VTA may reduce psychosocial stress-induced myocardial injury, a first step in exploring heart-brain interactions that may link psychosocial stress with negative cardiovascular disease outcomes.
Abstract 14965: 24-Hour Activity and Physical and Mental Health Related Quality of Life Among Women With Myocardial Infarction
Authors: Park Chorong , Larsen Britta A , Reynolds Harmony , Spruill Tanya M
Published: June 2023

Introduction:
After myocardial infarction (MI), many women experience depressive symptoms and reduced quality of life (QoL), both of which may be influenced by sedentary behavior (SB), physical activity (PA), and sleep. We examined associations of objectively-measured 24-hour activity with depressive symptoms and QoL, and simulated effects of reallocating 30 mins of SB with other activities on the outcomes.

Methods:
We used baseline data (≥ 2 months post-MI) of a multicenter trial of stress management in women with MI. Depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]), global QoL (PROMIS-mental/physical health), and disease-specific QoL (Seattle Angina Questionnaire-7 [SAQ-7]) were assessed. Participants wore wrist-actigraphs for 7 days. We used a GGIR R-package to classify 24-hour activity into SB, light PA, moderate-to-vigorous PA (MVPA), and sleep. Isotemporal substitution models were used to simulate time reallocation effects of SB on the outcomes adjusting for age, race/ethnicity, and income.

Results:
Figure 1 shows the 24-hour activity pattern in the sample (n = 87, age = 59.8 ± 12.8y, 67% non-Hispanic white). Greater total SB time (r = -0.34, p < .01) and prolonged (≥ 30mins/bout) SB bouts (r = -0.33, p < .01) were associated with worse SAQ-7 physical limitation but were not associated with other outcomes. The reallocation effects of SB to MVPA or sleep were associated with improved QoL and depressive symptoms (Figure 2).

Conclusion:
Women with MI had long total SB time with prolonged patterns, both of which are known to increase mortality risk. Breaking up SB bouts, and replacing SB with MVPA or sleep may improve QoL and depressive symptoms in women with MI.
Abstract 14967: Rate of Growth of the Right Ventricular Outflow Tract in Repaired Tetralogy of Fallot: A Cardiovascular Magnetic Resonance Imaging Study
Authors: Jurow Kelsey J , Gauvreau Kimberlee , Maschietto Nicola , Prakash Ashwin
Published: June 2023

Introduction:
Patients with repaired tetralogy of Fallot (rTOF) often require pulmonary valve replacement (PVR). Transcatheter PVR is a less invasive alternative to surgery but many right ventricular outflow tracts (RVOTs) are too large. Understanding the rate of RVOT growth may help optimize timing of referral. This study examined the growth of the RVOT over time in rTOF.

Methods:
We retrospectively analyzed serial cardiac MRI (CMR) data from 121 patients with TOF (median 3 MRIs per patient; range 2 to 10) to calculate the rate of increase in perimeter-derived diameters of the proximal infundibulum, middle RVOT, and distal RVOT at the point of PA bifurcation (Figure 1). The median age at first CMR was 14.7 years (range 3.3, 43.6 years) with a mean interval between first and last CMR of 8 years ± 3 years.

Results:
All parameters increased over time. The proximal RVOT increased at a rate of 4.1 mm per 10 years (p < 0.001); the mid and distal RVOT both increased at a rate of 3.1 mm per 10 years (p < 0.001) (Figure 2). The RVOT was larger on average in patients with a higher RV end diastolic volume (RVEDV) at first MRI and in patients with a higher pulmonary regurgitation (PR) fraction at first MRI. Patients with greater increases in RV EDV (Spearman correlation 0.48, p < 0.001) or PR fraction (Spearman correlation 0.27, p = 0.003) over time had greater RVOT growth.

Conclusions:
This largest-to-date serial CMR study of patients with rTOF detailed the rate of growth of the RVOT over time. More rapid growth was associated with higher PR fraction and larger RVEDV. This data may be useful in the design and clinical use of transcatheter pulmonary valves.
Abstract 14970: Early Observations of Population Characteristics for an Electrocardiogram-Enabled Smartwatch in the United States
Authors: Truong Hannah , Nayar Nandini , Zinzuwadia Aniket , Osman Noor , Goldberg Jana , Hanson Mark , Wessler Jeff
Published: June 2023

Introduction:
Over one-in-five Americans now use a smartwatch or fitness tracker and many wearables now offer electrocardiogram (ECG) capabilities. Expert interpretation of single-lead ECGs has demonstrated high diagnostic accuracy in atrial fibrillation (AF) detection, suggesting potential as a screening tool. Generalizability concerns remain given limited available data on age and geographic distributions of consumer smartwatch users.

Methods:
After obtaining FDA clearance, consumer smartwatch was launched in the United States in November 2021 and enabled users to transmit single-lead ECG recordings. Between November 2021 and May 2022, Heartbeat Health, a team with trained virtual cardiology providers, received and interpreted ECG recordings from 13,915 smartwatch users. Each reading was classified into five categories: 1) atrial fibrillation 2) normal sinus rhythm 3) high heart rate 4) low heart rate 5) possible other arrhythmia and 6) artifact. ECG findings were categorized by age and state Bloomberg Innovation Index (BII) for population analysis.

Results:
Of the 13,915 patients (average age 48.8 years) included in the analysis, 84.4% were under age 65 with an AF prevalence of 0.3%, and 15.1% of patients were over age 65 with an AF prevalence of 3.6%. States with higher innovation quintiles were associated with a higher share of users and users younger in age. Around 35.9% of our user population belonged to states in the first BII quintile but states in the first quintile only account for 25.6% of the total US population.

Conclusions:
Characterization of smartwatch ECG users revealed a higher share of users and younger users in states with higher BII, measured by density of technology companies, research & development, and postsecondary education. A large-scale trained provider review of smartwatch-enabled ECGs revealed rates of AF that were lower than the widely understood prevalence of AF in the US, suggestive of a potential demographic gap between consumers with access versus those that are more likely to surface undiagnosed AF via smartwatch ECG screening. With the growing penetration of consumer smartwatches, equitable distribution of innovation is increasingly important.
Abstract 14971: Loss of ZBTB46 Decreases BCL2A Expression and Increases Endothelial Cell Apoptosis
Authors: Williams Holly C , Wang Yu , Rezvan Amir
Published: June 2023

Introduction:
Endothelial cell (EC) activation, injury, and apoptosis in areas of the vasculature experiencing low and oscillatory shear stress (or disturbed flow) play a key role in the development and pathogenesis of atherosclerosis. In in vivo and in vitro studies, we have demonstrated that ZBTB46, a member of the BTB-ZF protein family of transcription factors, is down-regulated in ECs exposed to disturbed flow when compared to cells experiencing unidirectional laminar shear stress. Additionally, we have observed that germline deletion of ZBTB46 leads to decreased BCL2A expression in mouse carotid arteries. Given that ZBTB46 down-regulation occurs in areas of the vasculature prone to increased EC apoptosis and loss of ZBTB46 in vivo is associated with down regulation of anti-apoptotic protein BCL2A, we explored the role of ZBTB46 in EC apoptosis.

Hypothesis:
Loss of ZBTB46 negatively regulates transcription of the anti-apoptotic mediator BCL2A and sensitizes EC to apoptosis.

Methods:
Human aortic endothelial cells (HAEC) were transfected with either ZBTB46-siRNA or control siRNA, grown to 2 days post-confluence to induce ZBTB46 expression and then harvested for RNA. Gene expression was assessed by quantitative real-time PCR. In assays to measure apoptosis, siZBTB46 transfected cells, and corresponding controls were treated with various concentrations (0-400 micro molar) of hydrogen peroxide (H
2
O
2
) for 18 hours, stained for Annexin V and imaged by confocal microscopy

Results:
Down regulation of ZBTB46 using siRNA (siZBTB46) in HAEC led to a 78% ± 9% (SEM) reduction in BCL2A1 mRNA expression (n=4, p=0.004) when compared to controls (siCtrl). BCL2A1 downregulation also coincided with increased apoptosis in ZBTB46 deficient HAEC (siZBTB46 39% ± 2.9% v siCtrl 27% ± 3.5% n=6, p=0.026) as measured by Annexin V staining. Additionally, H
2
O
2
-induced apoptosis was exacerbated by loss of ZBTB46 in HAEC at 100 μM (siZBTB46 68% ± 2.1% v siCtrl 30% ± 3.1% n=5-6, p=0.001), 200 μM (siZBTB46 82% ± 1.2% v siCtrl 44% ± 3.2% n=4-5, p=0.001), and 400 μM H
2
O
2
(siZBTB46 88% ± 1.1% v siCtrl 58% ± 5.6% n=5-6, p=0.001).

Conclusions:
Loss of ZBTB46 in endothelial cells reduces BCL2A expression and increases the susceptibility of endothelial cells to apoptosis.
Abstract 14974: Diabetic Cardiomyopathy is Associated With Worsening of Quality of Life Long Before the Development of Overt Heart Failure: Lessons From the Baseline Analysis of the Arise-Hf Study
Authors: Urbinati Alessia , Perfetti Riccardo , Wang Stella , Persaud Sariah , Shendelman Shoshana , Januzzi James L
Published: June 2023

Introduction:
Diabetic Cardiomyopathy (DbCM) is a form of HF occurring in the absence of other causes of cardiac dysfunction such as hypertension, CAD, or valvular diseases in individuals with diabetes. The ARISE-HF study is designed to investigate the efficacy of AT-001, a novel aldose reductase inhibitor, in preventing the worsening of functional capacity in patients with DbCM.

Hypothesis:
The impact of DbCM on quality of life is greater than previously recognized, as patients with DbCM often adopt lifestyle changes to mitigate the impact of early symptoms. The hypothesis of the present study is that avoidance of physical activities in patients with DbCM may mask the clinical presentation of structural and functional myocardial changes that have occurred.

Methods:
The objective of the study was to investigate the physical activity levels in individuals with DbCM. We included patients with T2DM, age ≥60 years (or age ≥40 to <60 years with duration of diabetes ≥10 years or eGFR <60 mL/min/1.73 m
2
), LVEF ≥45% in the presence of either elevated NTproBNP levels or elevated hs-cTn or echocardiographic abnormalities. Patients enrolled in the study had an impaired functional capacity measured as peak VO
2
<
75% of predicted normal. Patients completed the Physical Activity Scale (PASE) questionnaire, a validated test designed to measure the amount of physical activity carried out during the prior week. Exclusion criteria included prior diagnosis of overt HF, history of CVD leading to cardiac dysfunction, elevated BP levels, and uncontrolled 2TDM (HbA1c>8.5%).

Results:
We evaluated 363 patients (mean age 67.5
+
7.1 years, 47% female, BMI 30.3
+
4.6, NTproBNP 113.4
+
252.7 pg/mL, and HbA1c 7.0
+
0.8%) with diagnosis of DbCM. PASE score (mean 157.9
+
94) was indicative of reduced physical activity and was associated (p<0.001) with peak VO
2
uptake (r= 0.31), underscoring the relationship between functional capacity and physical activity level.

Conclusions:
DbCM is a form of HF leading to decreased cardiac functional capacity. Many patients with DbCM have reduced their daily physical activities to mitigate the presentation of symptoms of fatigue; however, their quality of life is significantly affected by the disease even before the progression to overt HF.
Abstract 14981: Stk25 Regulates Cell Survival in Both Human and Mouse Models of Myocardial Injury
Authors: Zhang Xiaokan , Wang Bryan , Nash Trevor , Rao Jenny , Luo Lori , Fine Barry , Vunjak-Novakovic Gordana
Published: June 2023

Introduction:
Dysregulation of cardiac kinases occurs in cardiovascular diseases including hypertrophy, remodeling and ischemia injury. Serine/threonine protein kinase 25 (STK25) is a stress response kinase and putative tumor suppressor that regulates cell survival and metabolism through several signaling pathways, including LATS/3HIPPO and mTOR pathways.

Hypothesis:
STK25 regulates cell survival, metabolism and cardiac function in human cardiomyocytes and animal injury models.

Methods:
CRISPR-Cas9 was used to generate a homozygous knockout (KO) of STK25 in induced pluripotent stem cell (iPSC) which were then differentiated into cardiomyocytes (iPSC-CMs). STK25 was quantified in human left ventricular tissue from heart failure (HF) patients. Stk25 KO mice were generated by CRISPR/Cas9 mediated genome engineering in C57BL/6J background. Role of STK25 in gene expression, cell proliferation/apoptosis, metabolism and cardiac function were characterized.

Results:
Gene set enrichment analysis (GSEA) of differential gene expression obtained by RNA-seq was used to identify upregulation of several growth and metabolism pathways in STK25KO iPSC-CMs including oxidative phosphorylation, mTORC1 signaling and myogenesis. In functional assays, STK25 modulated cell cycle progression, proliferation, hypoxia induced apoptosis, and mitochondrial respiration in iPSC-CMs. n a myocardial infarction model of cardiac injury, loss of Stk25 in vivo led to improvements in cardiac function, reduced cardiomyocyte death and diminished fibrosis. STK25 expression is increased in HF patients. Furthermore, loss of function mutations in STK25 were discovered in atrial myxomas, demonstrating STK25 altered regulation in human heart diseases.

Conclusions:
STK25 regulates cardiomyocyte survival
in vitro
and
in vivo
and is aberrantly regulated in both hearth failure and atrial myxomas.
Abstract 14986: Reduced Arrhythmia Recurrence at One-Year When Using Active Esophageal Cooling
Authors: Joseph Christopher , Athill Charles , Ruppert Annie , Willms Danya , Francisco Gregory
Published: June 2023

Introduction:
The use of active esophageal cooling instead of traditional luminal esophageal temperature (LET) monitoring during left atrial ablation for the treatment of atrial fibrillation (AF) allows contiguous lesion placement with fewer partially-formed lesions and less catheter repositioning than required with LET monitoring. As a consequence, fewer electrical reconnections, and a lower rate of atrial arrhythmia recurrence, may result. We aimed to determine the association between esophageal protective strategy and recurrence of arrhythmia at one-year.

Methods:
We performed an IRB-approved review of an existing hospital registry to measure the association between recurrence of arrhythmia at one year follow-up and the use of active esophageal cooling as opposed to LET monitoring. Data were collected from ablations performed between 2017 and 2020. For each patient we recorded the type of esophageal temperature management, rhythm status at one-year follow-up, ejection fraction, and CHA
2
DS
2
-VASc score.

Results:
Data from a total of 247 ablations were collected. There were 95 ablations that occurred in the actively cooled group and 152 in the LET monitored group. Among those in the actively cooled group, the average CHA
2
DS
2
-VASc score was 1.8, and the average ejection fraction was 61%. In the LET monitored group, the average CHA
2
DS
2
-VASc score was 1.2 and the average ejection fraction was 61%. In the LET monitored group, there were 36 patients who had atrial arrhythmias at one-year follow-up, representing a 24% recurrence rate. In the actively cooled group, 11 patients had recurrence of arrhythmia at one-year, representing a 12% recurrence rate (P=0.02).

Conclusions:
Patients treated with active esophageal cooling during left atrial ablation had a significantly lower atrial arrhythmia recurrence rate at one-year follow-up when compared to patients provided with traditional LET monitoring during left atrial ablation procedures.
Abstract 14994: One-Year Mortality and Reoperation Among Patients With Infective Endocarditis After Transcatheter or Surgical Aortic Valve Replacement
Authors: Jacobs Mark , Abboud Alan , Muncan Brandon , Papamanoli Aikaterini , Parikh Puja B , Skopicki Hal , Kalogeropoulos Andreas P
Published: June 2023

Background:
With improving technology and experience, indications for transcatheter aortic valve implantation (TAVI) have expanded to include younger patients and those at moderate surgical risk, leading to increasing use of TAVI as an alternative to surgical aortic valve replacement (SAVR). As a result, post-TAVI infective endocarditis (IE) is increasingly common. Data on post-TAVI IE in comparison to post-SAVR IE outcomes are limited.

Methods:
Using data from the TriNetX Research Network, we identified (1) a cohort of patients who underwent TAVI between 1/1/2016 and 12/31/2020 (CPT procedure code 1021150) and developed IE (captured with ICD-10 codes I33, I38, or I39) after the procedure; and (2) a propensity score-matched cohort of patients who underwent SAVR (CPT procedure codes 1006141, excluding any associated transcatheter procedures) and developed IE. Both cohorts were required to have at least 1 week follow-up, i.e., deaths within 7 days of IE were excluded. We matched the cohorts for demographics and clinically relevant background characteristics.

Results:
We identified 713 patients with post-TAVI IE and 713 matched patients with post-SAVR IE. The baseline characteristics were well balanced, as indicated by standardized mean differences <0.1,
Table 1.
The Kaplan-Meier 1-year mortality between 7 days and 1 year (as deaths before 7 days were excluded) was 18.4% in the TAVI cohort (131 events) vs. 11.4% in the SAVR cohort (81 events), HR 1.62 (95%CI 1.23-2.14; P=0.001). Aortic valve reoperation was uncommon in both groups, with 13 and 10 events in the TAVI and SAVR groups, respectively (1.8% vs. 1.4%; HR 1.43, 95%CI 0.61-3.34; P=0.41).

Conclusions:
In this comparative, propensity-matched cohort study, 1-year mortality after an episode of IE was higher among TAVI recipients vs. their SAVR counterparts. Repeat aortic valve procedures were uncommon in both groups. Prospective studies are needed to elucidate the causes of excess mortality among TAVI recipients.
Abstract 14996: Single Cell Rnaseq Analysis Reveals a Two-Step Mechanism for the Reprogramming of Ventricular Myocytes to Pacemaker Cells by Tbx18
Authors: Fan Jinqi , Cho Hee Cheol
Published: June 2023

Background:
We have demonstrated that an embryonic transcription factor, TBX18, suffices to reprogram ventricular myocytes (VMs) to induced pacemaker cells (iPMs). Here, we sought to gain a mechanistic understanding of the reprogramming process using single cell (sc) RNAseq analysis.

Methods:
Cells from the ventricles of the neonatal rat heart were plated as monolayers, which consisted of both cardiomyocytes (CMs) and nonmyocytes, and were transduced with Adeno-GFP and Adeno-TBX18 in vitro. scRNAseq was performed at days (d) 3, 6, and 14.

Result:
TBX18-
CMs exhibited repression of chamber CM genes at d3, including those involved in cardiac muscle contraction and action potential. Markers of CM dedifferentiation (
Acta2 and Dab2
) were upregulated, while markers of chamber CM differentiation (
Mef2a
and
Rbm20
) were downregulated. Nodal pacemaker cell gene expression followed the CM dedifferentiation in TBX18-CMs, with the proportion of

Hcn4
+

CMs increasing gradually from 20.9% (d3) to 34.0% (d14), accompanied by increased expression of
Tbx3
and
Tbx18
. The proportion of iPMs (

Hcn4
+

,

Gja1
low

,

Nkx2-5
low
, Tnni3
high
, and Actn2
high

) in TBX18-CMs also increased from 3.6% at d3 to 6.4% at d14. Both TBX18-CMs and GFP-CMs exhibited a subpopulation of

Acta2
high

dedifferentiated CMs (deCMs), which were represented higher in TBX18-CMs compared to control. Among TBX18-CM subpopulations, the proportion of iPMs was the highest in deCMs (6.4% at d3 and 7.3% at d14). TBX18-deCMs were distinct from other TBX18-CM subpopulations in that extracellular matrix organization and Tgfβ signaling were enriched as well as higher expression of SP1 transcription factor which directly activates Hcn4 channel expression.

Conclusion:
Dedifferentiation and loss of CM function precedes nodal pacemaker cell gain of function during TBX18-induced somatic reprogramming of VMs to iPMs. Tgfβ signaling appears to figure prominently during this process.
Abstract 15003: A Circulating Genetic Signature in Psoriasis Associates With Future Cardiovascular Events
Authors: Garshick Michael S , Cornwell Macintosh , Drenkova Kamelia , Barrett Tessa A , Schlamp Maria Florencia , Ruggles Kelly , Rockman Caron , Reynolds Harmony , Berger Jeffrey
Published: June 2023

Introduction:
Psoriasis (PsO) is an inflammatory skin disease associated with cardiovascular (CV) disease (CVD). Multiple biomarkers are proposed to enhance risk assessment in PsO, yet the overlap between biomarkers of PsO and CV risk are incompletely understood. We therefore investigated the whole blood transcriptome in PsO, and prevalence and future risk of a CV event.

Methods:
PsO patients (n=37), without CV disease and 11 age-, sex-matched controls underwent whole blood RNA sequencing. The upregulated genetic signature in PsO vs controls was then evaluated in CVD cohorts: Group 1) women referred for cardiac catheterization for (n=26, median age 61 [IQR; 54 - 70] years) vs without (n=41, median age 62 [IQR; 58 - 69] years) an active myocardial infarction (MI), group 2) patients with peripheral artery disease followed longitudinally for major adverse CV or limb events (MACLE; n=106, median age 66 [IQR; 60 - 72] years, 74% male, median follow-up 2.5 years).

Results:
In the PsO cohort, median age was 44 (IQR; 34 - 51) years, 49% male, and ACC/AHA ASCVD Risk Score of 1.0% (0.6 - 3.4) with no significant difference vs controls. The median psoriasis area and severity index score (PASI) was 4.0 (IQR 2.9 - 8.2), PsO duration 15 (IQR; 9 - 25) years, with 36% on biologic therapy. Overall, 247 genes were upregulated and 228 downregulated in PsO vs controls (Figure 1A, p<0.05), and 1,302 genes positively and 1,244 genes negatively associated with PASI (Figure 1B, p<0.05). Seventy-three genes overlapped between these two comparisons (Figure 1C); key cytokine regulators were IL-6, IL-1β, and IFN gamma (Figure 1D). In the CVD cohorts, 50 out of 73 genes (68%, group 1) significantly associated with prevalent MI, and 29 (40%, group 2) with incident MACLE (Figure 1E).

Conclusions:
A whole blood transcriptomic signature of PsO diagnosis and severity was associated with prevalent MI and incident MACLE. These data have implications for understanding the link between PsO, systemic inflammation, and CVD.
Abstract 15014: Aberrant, Elevated Papillary Muscle and Left Ventricular Wall Forces Associated With Mitral Valve Prolapse Are Normalized by Surgical Neochordal Repair but Not by Transcatheter Edge-to-Edge Repair
Authors: Park Matthew H , Van Kampen Antonia , Nagata Yasufumi , Zhu Yuanjia , Pandya Pearly , Borger Michael A , Woo Y. Joseph J
Published: June 2023

Introduction:
Recent studies have linked mitral valve prolapse (MVP) to localized myocardial fibrosis and ventricular arrhythmia, and early imaging work has shown altered ventricular motion with papillary muscle (PM) traction in MVP and MitraClip patients. We aimed to biomechanically compare MitraClip and neochordal repair for MVP on PM forces
ex vivo
.

Methods:
We developed a force transduction system to measure the forces exerted on the PMs throughout the cardiac cycle in a left heart simulator (
Fig A
) with consistent pressures. Using a randomized, paired procedure with porcine MVs (n=4), we measured the hemodynamics and forces for control, diseased (P2 prolapse via chordal rupture), MitraClip repair (
Fig B, C, D
) (single P2 clip), and neochordal repair (P2 primary neochord on each PM) conditions.

Results:
We found that MitraClip PM forces (7.19 ± 0.31 N) are higher by 9.34% compared with those of controls (6.58 ± 0.21 N,
p<0.001
). This result is similar to MVP valves modeled by superior PM displacement, which showed 9.23% higher forces than those of controls (n=10,
p<0.001
). Moreover, MitraClip repaired valves showed PM force increases of 6.4% compared with forces of neochordal repair (6.76 ± 0.22 N,
p<0.001
), despite having similarly reduced regurgitation fractions (5.05% ± 1.98% vs. 4.25% ± 1.51%, respectively,
p>0.05
) compared with those of the diseased state (16.96% ± 3.04%,
p<0.001
) and controls (2.66% ± 0.87%). Additionally, neochordal repair valves had 2.79% higher forces compared to those of control valves (
p<0.001
).

Conclusions:
We discovered that MitraClip, while reducing regurgitation, does not restore aberrant forces on the PM induced in MVP to baseline or reduced levels, while neochordal repair does. Our work suggests that these elevated forces, associated with MVP and MitraClip, predisposes the MV to continued traction, which may present a long-term harm to patients by catalyzing localized fibrosis and ventricular arrhythmia.
Abstract 15032: Association of Race, Socioeconomic Status, and Incident Heart Failure: An Analysis of the National Health and Nutrition Examination Survey (nhanes)
Authors: Aladi Stanley , Youmans Quentin , Harap Rebecca , Wu Tingqing , Lewis Alana A , Brown Logan , Lewsy Sabra , Jackson Kamari , Maning Jennifer , Mensah Cheryl N , Ojeifo Oluseyi , Yancy Clyde W , Okwuosa Ike
Published: June 2023

Background:
Black Americans are disproportionately affected by heart failure (HF), including higher age adjusted mortality rates. Socioeconomic factors have been implicated as a driver of risk. This study seeks to further define the association of socioeconomic factors and risk of HF in a large heterogeneous cohort.

Methods:
This was an analysis of 58,555 participants of the National Health and Nutrition Examination Survey (NHANES) from 1999-2020. Participants were categorized by race and socioeconomic factors including education level and income. Education level was subdivided into high school education or less, and some college and greater. Using the income to poverty ratio (I/P), we defined three tiers of household income. High tier (I/P >2), Middle Tier (I/P 1.0-1.9), and low tier (I/P <1). Outcome variables were defined based on both examination data and survey questionnaire responses. Logistic regression was performed to ascertain odds ratios (OR) with 95% confidence intervals (CI).

Results:
In multivariable analysis, factors such as age (OR 1.06, CI 1.06-1.07; p=<.0001), and self-reported Black race (OR 1.2, CI 1.02-1.4; p=<.0001), were associated with incident HF. Medium tier (OR 1.5, CI 1.35-1.87; p= <.0001) and low tier household income (OR 1.7, CI 1.42-2.09; p= <.0001) had a higher odds of HF compared to high tier household income. Intra-racial multivariable analysis showed that among Black participants, low tier household income (OR 1.8, CI 1.2-2.6; p=0.001) was associated with incident HF. No difference among gender or education attainment was observed. Interracial multivariable analysis based on household income showed that Black participants in the low tier of household income (OR 1.36, CI 1.01-1.85; p=0.04) had an increased odds of HF compared to Non-Black at similar household income. Black and Non-Black participants had similar odds of HF at medium and high tier household incomes.

Conclusion:
In this analysis, Black participants had higher odds of incident HF compared to other participants. Factoring in household income, Black participants in the lowest income tier were the most vulnerable. Targeting income inequality may help address racialized HF disparities.