bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12847: The Heart Bus: A Mobile Patient-Centered Approach to Improve Early Diagnosis of Heart Failure in the Community
Authors: Svedlund Sara , Lagerstrom Fermer Maria , Valastro Barbara , Ramne Anna , Michaëlsson Erik , Rudvik Anna , Westberg Karin , Hedner Henrik , Nori Radna , Gan Li-ming
Published: December 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is associated with poor quality of life and considerable morbidity and mortality risk. Early diagnosis is expected to improve clinical outcomes, but requires imaging and laboratory analyses with frequent hospital visits. We developed a mobile care unit, the Heart Bus, to improve early diagnosis of HF.

Methods:
The Heart Bus was a 70 m
2
trailer with examination rooms, cardiac ultrasound, exercise testing equipment, a clinical laboratory, and 4 staff. During 2020-2022, the Heart Bus team reached out to the population in local newspapers, via HF patient digital platforms, and visited locations in the West Coast of Sweden. Eligible participants had suspected signs or symptoms of HF. Participants underwent echocardiography and tests for cardiopulmonary exercise, vascular function, adenosine-stress coronary flow reserve, and routine biochemistry and haematology. Molecular and physiological deep phenotyping were also performed in the Heart Bus to facilitate future patient stratification and precision medicine (data to be presented Nov 2023).

Results:
Of 218 participants screened over 18 months (12/month), 200 were included. Most participants actively reached out to take part. Twenty three participants (11.5%) had HFrEF, 54 (27.0%) had HFmrEF, and 62 (31.0%) had HFpEF; 70 (35.0%) had a previous HF diagnosis. Of the remaining patients, 60 (30.0%) had intermediate risk of HFpEF. The phenotypes of the EF-stratified HF subgroups were similar. However, participants in the HFpEF cohort had more women (
p
< 0.001), lower lung volume (
p
< 0.01), higher pulse wave velocity (
p
< 0.01) and poorer kidney function (
p
< 0.05) than those with HFrEF.

Conclusions:
The Heart Bus mobile clinic identified large numbers of patients with HF and may represent a cost-effective way to early HF diagnosis also for underserved communities, those located remotely, or have other thresholds for admittance to HF clinics.
Abstract 12857: Electrocardiographic Findings in Women With Ischemic Sudden Cardiac Death and Anatomic Left Ventricular Hypertrophy
Authors: Hookana Ida , Eskuri Anette , Holmstrom Lauri , Vahatalo Juha , Kentta Tuomas , Tikkanen Jani , Pakanen Lasse , Perkiomaki Juha , Huikuri Heikki , Junttila Juhani
Published: December 2023

Background:
Sudden cardiac death (SCD) is a major mode of death worldwide. Previous SCD studies have shown that left ventricular hypertrophy (LVH) is a risk factor for SCD, especially in the presence of myocardial scarring or ischemia. Due to the lower incidence, women are often underrepresented in SCD studies and therefore, most recognized SCD risk factors are biased towards men.
Aim:
The aim of this study was to investigate sex-specific ECG findings in subjects with ischemic SCD and LVH.

Methods:
The study population was derived from the FinGesture study, which has collected all SCD cases from Northern Finland 1998-2017. All SCD cases underwent medicolegal autopsy to determine the cause of death. In the present study, we selected SCD cases with coronary artery disease (CAD) and anatomic LVH at autopsy, of whom antemortem electrocardiogram (ECG) was available for 483 subjects (24.4 % women; 75.6 % men). Antemortem recorded ECGs were obtained from medical records and independently analyzed by two investigators.

Results:
The prevalence of pathological Q-waves (11.9 % vs. 22.1 %, p = 0.016) and fragmented QRS (fQRS) (43.9 % vs. 56.4 %, p = 0.033) was lower in women compared to men. In addition, women were less likely to have prolonged QTc duration (17.8 % in women vs. 32.3 % in men, p = 0.003). The only ECG finding that appeared as more prevalent in women with anatomic LVH was ECG-LVH by Cornell’s criteria (26.4 % vs. 12.4 %, p = 0.002). The prevalence of having abnormal ECG was slightly lower in women (82.2 %) compared to men (89.2 %), p = 0.054. There were no significant differences between sexes when comparing the prevalence of anatomic LVH in subjects with ECG-LVH and ischemic SCD (90.6 % in women vs. 84.9 % in men, p = 0.524).

Conclusions:
Except for ECG-LVH by Cornell’s criteria, women with ischemic SCD and anatomic LVH were less likely than men to have ECG findings that are often associated with an increased risk of SCD.
Abstract 12860: A Novel Cardiac Presentation of a Genetic Syndrome
Authors: Shah Parth A , Bhandari Bishal , Alsaid Amro
Published: December 2023

Introduction:
Cute Syndrome is caused by a missense mutation in SCN8-A which encodes voltage gated sodium channel alpha subunit 8 (Nav1.6). Gain of function mutations trigger epileptic encephalopathy, while loss of function mutations are associated with cerebellar ataxia and cognitive problems
1
. While these channels are essential for progression of action potentials across the cardiac circuit, SCN8-A mutations are not associated with arrhythmias. Meanwhile, SCN5-A mutations have been implicated in heart block, LQTS, Brugada syndrome, and ventricular fibrillation. Here we describe a case of heart block and sinus node dysfunction in a patient with SCN8-A mutation.

Presentation:
A 19 year old male with past medical history of SCN8A mutation admitted for characterization of seizures. He has had focal seizures since the age of 13 with multiple admissions for seizures. He had new staring spells with shaking of his hands and inability to walk multiple times a week. He was admitted for Long Term EEG and was noted to have two episodes of loss of consciousness with progressive bradycardia followed by sinus pauses. He urgently had a temporary pacemaker placed followed by placement of a PPM. He has remained seizure free since his PPM implantation.

Discussion:
Voltage gated Sodium channels are an integral part of the cardiac action potential. SCN8-A encodes Nav1.6. A mutation in this gene, primarily expressed in neurons but has also been seen in cardiac tissue, could cause arrhythmias. Human mutations have been associated with intellectual disabilities and seizure disorders
1,2,3
. Mouse models have shown that null mice have prolonged cardiac action potentials, suggesting role in cardiac arrythmias
4
. There have been no documented human cases of SCN8-A mutations with arrhythmias. Our patient's seizures were thought to be due to the neurological manifestations of his mutation. Evaluation of cardiac and EEG monitoring determined that sinus pauses preceded seizures, and he has been seizure free since his PPM. This case demonstrates the need for further research to characterize cardiac manifestations of SCN8-A mutations and patients with the mutation may benefit from further cardiac evaluation.
Abstract 12864: Trim69 Alleviates Heart Aging and Mitochondrial Dysfunction by Restoring Mitophagy Through P53-Related Pathway
Authors: Yang Jian
Published: December 2023

Introduction:
Cardiac aging is defined as the heart structural and functional abnormality, manifesting as the aging-associated functional decline and the aging phenotypes. Trim69 is an E3 ubiquitin-protein ligase representing the potential to alleviate cardiac aging through poorly defined mechanisms.

Hypothesis:
Whether Trim69 signaling improves cardiac aging, and if so to further explore the underlying mechanism.

Methods:
The SD rats were subjected to subcutaneous injection of low-dose D-gal in the nape for 8 weeks to induce senility. The recombinant lentivirus was transmitted by myocardial multipoint injection to overexpress Trim69
in
vivo.
The assessment of cardiac function and aging-associated phenotypes were enforced through an ECG, β-gal staining, Masson staining, WGA staining, and western blot. Cardiac mitochondrial structure and mitophagy were observed through electron microscopy
in
vivo
, which were detected by a mitophagy detection kit and JC-1 staining
in
vitro
. H9C2 cardiomyocyte line derived from rats' embryonic stem cells was used to explore the protective effects and mechanism of Trim69 against D-gal-induced cardiac aging and mitochondrial dysfunction.

Results:
After 8 weeks of D-gal induction, the heart function of rats significantly declined, with marked manifestations of senility including positive for β-gal staining, increased oxidative stress, noticeable myocardial hypertrophy, and progression of myocardial fibrosis. Trim69 overexpression alleviated D-gal-induced cardiac dysfunction and mitochondrial damage, accompanied by mitophagy recovery. Mechanistically, Trim69 directly binds with P53 and promotes its ubiquitination and degradation, reversing the D-gal-induced mitophagy suppression via Parkin/Pink1 axis.

Conclusions:
Overexpression of Trim69 could promote ubiquitin degradation of P53, which further inhibits the accumulation of P53, therefore alleviate the cardiac aging and mitochondrial dysfunction.
Abstract 12880: Riluzole Significantly Lowers Heart Failure Incidence
Authors: Radwanski Przemyslaw , KIM KIBUM , Kim Sodam , Katana Margaret , Munger Mark A
Published: December 2023

Objective:
Reduction of intracellular sodium accumulation through inhibition of late Na
+
current has been recognized as a target for cardiac calcium handling which underlies myocardial contractility and relaxation in heart failure (HF). This approach may augment neurohormonal balance to evade HF progression. Riluzole , a brain-type Na
+
channel blocker with enhancement of Ca
2+
-activated K
+
channel function, used for management of amyotrophic lateral sclerosis (ALS). The study aim was to investigate whether riluzole lowers HF incidence.

Methods:
Rates of incident HF were compared using a commercial insurance and Medicare supplement claims databases. Patients who filled a prescription for riluzole (treatment) between 06/2009 and 12/2019 were compared to those with no-riluzole (control). We excluded HF patients during the 180-day baseline period. Study endpoint was the first diagnosis of HF from the index riluzole prescription or ALS diagnosis. HF onset was compared using Kaplan-Meier cumulative incidence estimates and multivariable Cox proportional hazard regression model.

Results:
The study cohort consisted of 4,324 riluzole and 6,415 ALS control patients. The 24-month cumulative incidence of HF onset for riluzole vs. control patients was 4.71% vs. 8.73%, calculating hazard ratio (HR) [95% CI,
p
-value] of 0.399 [0.297 - 0.537, p<0.001]. Adjusting for patient demographics and comorbid conditions, the 24-month HR: 0.495 [0.367 - 0.668, p<0.01]. The lower rate of HF onset was independent of age (<65 and ≥65 age groups, HR: 0.378 [0.234 - 0.611, p<0.01] and 0.611 [0.413 - 0.881, p<0.01]) respectively.

Conclusions:
Riluzole is associated with a lower rate of HF onset, suggesting a potential prevention strategy for early management.
Abstract 12902: Supraventricular Tachycardia During Pregnancy is Independently Associated With Adverse Obstetrical Outcomes
Authors: Bekiaridou Alexandra , Coleman Kristie M , Sharma Nikhil , George Deepika , Liu Yan , Gianos Eugenia , Rosen Stacey E , Mieres Jennifer H , Mountantonakis Stavros
Published: December 2023

Introduction:
Supraventricular tachycardias (SVT) are the most frequently encountered arrhythmias in pregnancy, however, their clinical significance is unclear.

Hypothesis:
We report the prevalence, describe the management and explore the association between SVT and adverse obstetric outcomes in women with structurally normal hearts.

Methods:
This is a case-control study of primiparous and multiparous women without history of cesarean section (CS), and no known cardiac diagnosis admitted in labor to one of 8 Northwell Health hospitals between January 2015 and August 2022. The study group consisted of women with at least one SVT episode during pregnancy and the control group was randomly selected in a 4:1 ratio. Multivariate analysis was used to examine the association between occurrence of SVT during pregnancy and incidence of cesarean section (CS), preterm labor (PTL), and length of stay (LOS).

Results:
Of 141,769 women meeting the inclusion criteria, SVT diagnosis was confirmed in 122. Of those, 76 (age 33.2±4.8 years) had at least 1 symptomatic episode during pregnancy. For the women with known SVT diagnosis prior to pregnancy, medical therapy with any antiarrhythmic agent was not associated with reduction of SVT recurrence during pregnancy (OR 1.07, 95% CI 0.41-2.80 p=0.89). On the contrary, catheter ablation prior to pregnancy was associated with significant reduction of SVT recurrence (OR 0.09, 95% CI 0.04-0.23, p<0.0001). Women with SVT during pregnancy had a higher incidence of CS (39.5% vs 27.0%. p=0.03), and PLT (30.3% vs 8.6%, p<0.001) compared to the control group. After adjusting for age and parity, SVT during pregnancy was independent predictor of CS, particularly elective CS (OR 2.89 95% CI 1.06-7.89) and PTL (OR 4.37 95%CI 2.30-8.31).

Conclusions:
SVT occurs in about 1 in every 1,000 women during pregnancy and is associated with higher rates of CS, particularly scheduled, and PLT. Any history of SVT should be sought and addressed during preconception counselling and SVT episodes during pregnancy should be approached in a multidisciplinary way to mitigate the risk of CS and associated complications.
Abstract 12911: Life’s Essential 8 and Heart Failure: The Million Veteran Program
Authors: Li Yanping , Nguyen Xuan-Mai T , Treu Timothy M , Wang Dong D , Ho Yuk-lam , Houghton Serena , Posner Daniel , RAGHAVAN SRIDHARAN , Pyatt Mary , Gagnon David , Whitbourne Stacey B , Gaziano John , Djousse Luc , Joseph Jacob , Wilson Peter , Kim Kelly
Published: December 2023

Background:
Heart failure (HF) incidence has increased over past decades and is associated with poor quality of life, increased comorbidities, and high treatment costs. Prevention for HF warrant a major public health priority.

Aim:
To quantify the association of Life’s Essential 8 (LE8) score with HF.

Methods:
LE8 score (0-800) was developed based on the AHA guidelines among 348,311 Veterans who enrolled in the VA Million Veteran Program (MVP) (2011-2021) and free of HF at baseline. Cox proportional hazard models were used to calculate the hazard ratios (HR) with their 95% confidence intervals (CI) for first incident HF event, and HF subtypes (HF with reduced ejection fracture (HFrEF) and HF with preserved EF (HFpEF)) across categories of LE8 score. The population attributable fraction (PAF) was calculated to estimate the proportional reduction in HF events that would occur if LE8 was changed to the ideal level.

Results:
A total of 31,397 HF events were recorded over 1.8 million person-years of follow-up. LE8 score was negatively associated with incidence of HF, HFrEF and HRpEF, even after extensive adjustment for potential confounders (
Figure 1A
). The multivariate-adjusted HR for HF was 0.76 (95% CI: 0.73-0.78), 0.63 (0.61-0.65), 0.52 (0.50-0.54), 0.41 (0.39-0.43), 0.34 (0.32-0.36), 0.28 (0.27-0.30), and 0.23 (0.21-0.25), respectively, among Veterans whose LE8 score was 350-, 400-, 450-, 500-, 550-, 600- and ≥650, respectively, as compared to those with LE8 score <350. The PAF for HF was 7.1%, 10.3%, 15.1%, 15.8%, 17.1%, 17.5% 18.4%, and 49.1% for not ideal sleep, diet, lipid, activity, BMI, smoking, glucose/HbA1c, and blood pressure, respectively, with an estimated joint PAF of 83.2% for total HF, 79.5% for HFrEF and 90.1% for HFpEF for not ideal of any LE8 (
Figure 1B
).

Conclusion:
Greater adherence to a healthy LE8 lifestyle could be a key component in prevention of HF among Veterans. Assuming everyone follows a lifestyle meet ideal LE8, majority of HF cases will be prevented.
Abstract 12912: Effect of Real-Time Ambulatory Electrocardiography on Time-to-Intervention
Authors: Feuerborn Melissa , Torre Michael , Lyons Ann , Bunch T J , Steinberg Benjamin A
Published: December 2023

Background:
Mobile cardiac telemetry (MCT) and event monitors are ambulatory electrocardiography (AECG) monitors to aid in the detection/diagnosis of arrhythmias. They are unique in their real-time alerts to clinicians. This contrasts with Holter monitoring, which is continuous but where results are not available until after completion of the exam, uploading, and clinician over-read. There is limited data on relative benefit for time to electrophysiology procedure and interventions.

Hypothesis:
Does real-time monitoring of AECG reduce the time to cardiac implantable electronic device procedure, ablation procedure, or healthcare encounter when compared to AECG without real-time monitoring?

Methods:
This is a retrospective observational analysis of University of Utah Health patients who underwent AECG studies from 2010-2022. The study cohort was stratified by patients with an ambulatory ECG that provides real-time event notification (CEM and MCT; hereafter Non-holter) versus those that do not (Holter). The outcomes of interest were cardiac device implantation, ablation procedure, and ER/hospitalization within 12 months, analyzed based on time-to-event using log-rank tests.

Results:
We identified 50 patients in the Holter group and 137 for the Non-holter group. The groups had similar baseline characteristics in terms of age, gender, and co-morbidities. The mean number of days to device implant was 68.1 and 66.36, to ablation procedure was 77.68 and 67.77, and to ER/hospital visit was 61.12 and 55.38 in the Holter and Non-holter groups respectively (Figure).

Conclusion:
There was not a statistically significant difference between AECG monitoring in real-time (Non-holter) and those without (Holter), however, there was a trend toward decreased time to intervention in the Non-holter group for each of the three outcomes. Future, larger cohorts may provide adequate power to determine if real-time monitoring does reduce time to the studied interventions.
Abstract 12914: Echocardiographic Assessment of Ventricular Stiffness in Single Right Ventricle Physiology: A Validation Study
Authors: Chowdhury Shahryar M , Menick Donald R , Bandisode Varsha , Rhodes John , Graham Eric M , Atz Andrew M
Published: December 2023

Background:
Ventricular stiffness is associated with outcomes in patients with single right ventricle (SRV) physiology. However, echocardiographic (echo) assessments of ventricular stiffness are limited in this population. The objective of this study was to assess if echo measures of diastolic function are associated with invasive reference standard measures of ventricular stiffness derived from pressure-volume loop (PVL) analysis.

Methods:
Patients with SRV physiology undergoing pre-Fontan heart catheterization were prospectively enrolled. PVLs were obtained via microconductance catheters. The reference standard measure of ventricular stiffness, β, was obtained after balloon occlusion of the vena cavae. Echo measures were derived from spectral and tissue Doppler and 3D echo. Conceptually, patients with abnormal active ventricular relaxation and small end-diastolic ventricular volumes (EDV) are at risk for having increased passive ventricular stiffness. Therefore, the echo measurement of interest was lateral E:e’ divided by EDV indexed to body surface area (E:e’/EDVi).

Results:
19 patients included in the study. Mean age was 4.1 ± 0.7 years. Median β was 0.022 mL
-1
(IQR 0.012, 0.062). Median lateral E:e’/EDVi was 0.10 mL
-1
/m
2
(IQR 0.07, 0.15). The correlation between lateral E:e’/EDVi and β was r = 0.65, p < 0.01 (Figure). No other correlations existed between echo measures of diastolic function and invasively derived ventricular stiffness.

Conclusion:
Lateral E:e’/EDVi correlates reasonably well with the reference standard measure of ventricular stiffness in SRV patients prior to the Fontan operation. The clinical utility of assessing lateral E:e’/EDV in SRV patients should be further explored regarding its potential to identify novel insights into the pathophysiology of SRV heart disease, detect changes in stiffness after medical/surgical intervention, and to investigate new echo predictors of outcome.
Abstract 12925: MICU Overflow Patients in the Cardiac Intensive Care Unit: Insights From the Critical Care Cardiology Trials Network Registry
Authors: Isath Ameesh , Bali Atul , Mahmood Uzair , Namrata FNU , Berg David , Bohula Erin A , Morrow David , Cooper Howard A ,   on behalf of the CCCTN Investigators.
Published: December 2023

Background:
The cardiac intensive care unit (CICU) is designed to manage critically ill patients (pts) with acute cardiovascular (CV) conditions, but may be the site of care for pts with non-CV critical illness when medical ICU (MICU) beds are unavailable.

Methods:
The Critical Care Cardiology Trials Network (CCCTN) is a multicenter registry of consecutive admissions to CICUs in North America coordinated by the TIMI Study Group. Pts with no acute or major cardiac issues were designated as MICU overflow and were compared to those admitted with acute CV illness. A generalized mixed-effect regression model was used to adjust for age, sex, Sequential Organ Failure Assessment (SOFA) score and cardiac arrest while accounting for variability among centers.

Results:
Among 18,006 CICU admissions, 778 (4.3%) were MICU overflow, with a range of 0% to 26% among centers. MICU overflow rates trended lower over time
(Fig-A)
. In comparison to admissions with acute CV illness, MICU overflow patients were younger (60.0 vs 67.0 y, p<0.001) and more likely to be female (45.6 vs 36.7%, p<0.001). Comorbidities differed markedly between the 2 groups
(Fig-B)
. Presentation with cardiac arrest was more common among admissions with acute CV illness (12.9% vs 4.5%, p<0.001). MICU overflow admissions had higher SOFA scores than those with acute CV illness (5.0 vs 3.0, p<0.001). Resource utilization is shown in
Fig-C
. ICU LOS was similar (2.0 vs 2.2d, p=0.4). MICU overflow status was associated with a trend in CICU mortality (adj-OR 1.19, 95% CI 0.93-1.53, p=0.16) and significantly higher hospital mortality (adj-OR 1.69, 95% CI 1.36-1.73, p<0.001)
(Fig-D)
.

Conclusions:
MICU overflow pts constitute a meaningful number of admissions to CICUs. These pts have more multi-system disease, greater baseline organ dysfunction, and higher hospital mortality than pts with acute CV illness. These findings reinforce the need for multidisciplinary CICU teams with expertise in all facets of critical care.
Abstract 12936: Quality of Life Assessments as Inclusion Criteria in Heart Failure Clinical Trials
Authors: Dimond Matthew , Khan Mohammad S , Fiuzat Mona , Cleland John G , Bhatt Ankeet , Psotka Mitchell , Anker Stefan D , Butler Javed , Felker Michael , Mark Daniel B , Carson Peter E , Abraham William T , Ahmad Tariq , Lindenfeld Joann , Vaduganathan Muthiah , Whellan David J , Vardeny Orly , Solomon Scott , Lewis Eldrin F , Filippatos Gerasimos , OConnor Christopher M
Published: December 2023

Background:
Patient-reported quality of life (QoL) assessments, such as the Kansas City Cardiomyopathy Questionnaire (KCCQ) or Minnesota Living with Heart Failure Questionnaire (MLHFQ), reflect an individual’s health status and symptom severity at a given timepoint, and may have utility as inclusion criteria in heart failure (HF) clinical trials.

Method:
The Heart Failure Collaboratory-Academic Research Consortium, a group of stakeholders including patients, investigators, and representatives from government and industry, convened to review data from multiple HF clinical trials discuss the use of patient reported QoL-based inclusion criteria in clinical trials of HF.

Result:
Patient-reported QoL assessments, such as the KCCQ, have high test-retest reliability and, in contrast with the physician-assigned New York Heart Association (NYHA) class, are not subject to clinician bias or influenced by knowledge of prognostic variables such as Left Ventricular Ejection Fraction (LVEF) or N-terminal pro B-type Natriuretic Peptide (NT-proBNP). The U.S. FDA has qualified KCCQ as an effective clinical outcomes assessment for HF, and recent clinical trials that demonstrated substantial reductions in morbidity and mortality also showed improvements in KCCQ scores, provided patients had a decrement at baseline. However, KCCQ use is limited by both complicated clinical interpretability, with total symptom score consisting of aggregate scores from different physical and symptomatic domains and uncertainty around the threshold of clinically important difference, and by its length, with average completion time of 5 to 8 minutes.

Conclusion:
Patient-reported functional assessments have potential as inclusion criteria in clinical trials of HF by ensuring the enrollment of patients with a diminished QoL who have the potential to improve in response to therapeutic intervention, especially in clinical trials with QoL-based endpoints.
Abstract 12940: The Power of Engagement: How Stakeholder Engagement Influenced the Design and Conduct of a Clinical Trial With Home Health Aides and Their Heart Failure Patients
Authors: Espinosa Cisco G , Vergez Sasha , McDonald Margaret , Safford Monika M , Wiggins Faith , Lee Ann , Tobin Jonathan N , Feldman Penny , Banerjee Samprit , Dell Nicola , Sterling Madeline R
Published: December 2023

Background:
Although home health aides and attendants (HHAs) frequently provide care to community-dwelling adults with heart failure (HF), they have rarely been the focus of interventions aimed at improving patient outcomes. Engaging HHAs and other key home health care stakeholders in the research process is essential to designing user-friendly interventions and feasible clinical trials that can leverage their role in delivering care, as well as identifying effective implementation strategies that improve service delivery and patient outcomes.

Aim:
Herein, we aimed to demonstrate how stakeholder engagement influenced all aspects of HF clinical trial design with this marginalized workforce.

Methods:
This study involved an academic community partnership between Weill Cornell Medicine and two non-profit organizations, VNS Health, a large, non-profit organization that provides home care, population and care management, community health services, and hospice care in New York, NY; and the 1199SEIU Training and Employment Fund, the largest union of healthcare workers in the US that provides training to HHAs. A stakeholder-engaged research approach was used to a) develop a novel intervention that trains HHAs on HF and integrates them into the care team through an mHealth application, and b) design a pilot randomized clinical trial (RCT) testing this intervention among HHAs caring for adults with HF who receive home care from VNS Health.

Results:
Over the course of four years, stakeholders in home health were engaged in every aspect of the research process, from the motivation and rationale for the study, to intervention development and refinement, selection of outcomes, and planning and conduct of an ongoing pilot study for a future pragmatic RCT [Table 1].

Conclusion:
This study offers an example and methods for how stakeholders can be engaged in the design, conduct and dissemination of a trial aimed at improving HF care.
Abstract 12945: Six-Month Adherence Among Early Inclisiran Initiators vs. Anti-PCSK9 mAbs Users: A Retrospective Analysis of US Claims Databases
Authors: Niu Charlene , Parlapalli Akhil , Neenan Joseph , Ma Xinshuo , Osei-Wusu Abena , Park Jina , McElligott Sean
Published: December 2023

Introduction:
Poor adherence with statins is an obstacle in achieving LDL-C targets for patients with atherosclerotic cardiovascular disease (ASCVD). Inclisiran is a first-in-class, long-acting, small-interfering RNA approved as an adjunct to diet and maximally tolerated statin for adults with ASCVD or heterozygous familial hypercholesterolemia who require additional LDL-C lowering. It is initially administered subcutaneously by an HCP, again at 3 months and then twice yearly. Real-world studies assessing adherence of inclisiran are limited.

Hypothesis:
This study evaluated treatment adherence at 6 months for patients who newly initiated inclisiran, alirocumab (every 2 weeks or 1/month) or evolocumab (every 2 weeks or 1/month) since 2022.

Methods:
This retrospective, observational study utilized the US Komodo Health database from 1/1/21 - 2/8/23. Komodo Health is a nationally representative longitudinal database that captures 330 million patients in the US from open and closed administrative databases. Patients were aged ≥18 years, had 12 months of continuous enrollment (CE) before the index date, 6 months CE after the index date and a first claim for inclisiran, alirocumab, or evolocumab in the identification period (1/1/22 - 10/31/22). Adherence was defined as the proportion of days covered (PDC): the number of days covered by the drug divided by the observational period (6 months after index date). Poor adherence was defined as PDC <80%.

Results:
A total of 981 patients had ≥6 months of CE after the index date and were in the inclisiran cohort;11,330 patients were in the alirocumab cohort and 30,515 in the evolocumab cohort. Mean (SD) 6-month adherence was highest for inclisiran at 0.85 (0.22) followed by 0.72 (0.30) for alirocumab and 0.70 (0.30) for evolocumab. The proportion of patients with high adherence (PDC ≥0.8) was 69.9% for inclisiran, followed by 51.0% for alirocumab and 48.6% for evolocumab. Of patients in the inclisiran cohort (n=981), 70.9% received a second dose with a mean time of 90.9 (32.0) days between doses.

Conclusions:
Early evidence post launch shows patients initiating inclisiran had higher adherence vs anti-PCSK9 mAbs. Inclisiran is a new option for patients with ASCVD who may have difficulty reaching their LDL-C target.
Abstract 12950: A Nationwide Remote Patient Intervention Hypertension Program: Can Remote Patient Monitoring and a Multi-Disciplinary Team of Clinicians Improve Blood Pressure Control?
Authors: Feldman David I , Campbell Marcus L , Babikian Sarine , Curnow Randall , Feldman Theodore , Fudim Marat
Published: December 2023

Introduction:
Traditional methods for diagnosing and treating HTN, which is the most common modifiable risk factor accounting for ASCVD in the US, have been ineffective. Innovative solutions, like remote patient monitoring (RPM), can transform how we provide longitudinal care for patients with HTN.

Hypothesis:
An advanced practice provider led HTN program, which leverages RPM and technology-enabled treatment protocols, can provide a scalable solution for optimizing HTN management nationwide.

Methods:
Cadence is a healthcare technology organization that enrolled patients into a virtual HTN program in PCP clinics in 11 states across the US from February 2022 to April 2023. Eligible patients were Medicare enrollees who had a diagnosis of HTN based on ICD-10 codes, mean blood pressure (BP) >140/90 (using last 3 EMR-based vitals) and were enrolled for at least 30 days. Using daily vitals from a cellular enabled BP cuff and scheduled visits, a team of multidisciplinary clinicians leveraged technology-enabled clinical protocols to facilitate optimization of HTN control. A two-sample t-test was used to detect a difference in mean BP.

Results:
A total of 4006 patients were enrolled (mean age 73 +/- 9, 70% White) with a baseline BP of 144/83 mmHg. The total reduction in systolic BP (SBP)/diastolic BP (DBP) was 9/6 (p<0.001) in the last week compared to the first week (mean follow-up of 136 +/- 92 days). The total number of vitals recorded, clinical visits and phone calls completed, and high acuity clinical alerts resolved is depicted in Figure 1A. The SBP/DBP reductions by different BP strata are depicted in Figure 1B. There was a ~2x increase in the number patients at goal (BP<130/80) in the last week compared to the first week (31% vs. 15%; p<0.001).

Conclusions:
A remote patient monitoring HTN program not only can improve the diagnosis of hypertension, but also can significantly reduce blood pressure, and in doing so help more patients achieve guideline recommended BP goals.
Abstract 12953: Targeting NEDD9 and SMAD3 in the Pathogenesis of Chronic Thromboembolic Pulmonary Hypertension
Authors: Sangam Shreya , Qi Wei , Samokhin Andriy O , Maron Bradley A
Published: December 2023

Background:
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by unresolved pulmonary thrombi due, in part, to impaired fibrinolysis. We showed previously that oxidation of the Cas protein NEDD9 at cysteine-18 (Cys
18
) inhibits complex formation between NEDD9 and the anti-fibrinolytic transcription factor SMAD3 in human pulmonary artery endothelial cells (HPAECs). However, the effect of NEDD9-Cys
18
oxidation on SMAD3 bioactivity in HPAECs is not known.

Hypothesis:
NEDD9-Cys
18
oxidation increases bioavailable SMAD3, which upregulates
SERPINE1
that encodes plasminogen activator inhibitor (PAI)-1 to inhibit fibrinolysis pathways in HPAECs.

Methods/Results:
To assess the effect of SMAD3 on
SERPINE1
transcription, HPAECs were transfected with cDNA-SMAD3 (1 μg/μl) for 72 hr to induce SMAD3 overexpression. Compared to vehicle (V) control, cDNA-SMAD3 increased PAI-1 and
SERPINE1
expression by 35% (P=0.004) by immunoblot and 70% (P=0.003) by real-time PCR, respectively (N=3). To determine the effect of NEDD9 inhibition on SMAD3 activation, we analyzed the ratio of P-SMAD-Ser423/425:SMAD3 by immunoblot. Compared to scrambled RNA (scRNA), transfection with siRNA against NEDD9 (siNEDD9) for 48 hr increased the relative quantity of activated SMAD3 by 1.4-fold (P=0.006) and upregulated PAI-1 (P=0.004) expression by 1.7-fold in HPAECs (N=4). Next, we monitored the effect of oxidant stress on SMAD3 bioactivity. Compared to V-control, the expression of NEDD9, total SMAD3, and P-SMAD3 was increased by 66% (P=0.04), 81% (P=0.03), and 29% (P=0.04), respectively, in HPAECs treated with hydrogen peroxide (H
2
O
2
) (500 μM) for 20 min. Next, the effect of NEDD9 silencing on H
2
O
2
accumulation in HPAECs was measured by Amplex Red assay. HPAECs were transfected with scRNA or siNEDD9 for 48 hr followed by measurement of H
2
O
2
production. Compared to scRNA, NEDD9 silencing significantly decreased H
2
O
2
concentration by 56% (N=4, P=0.02).

Conclusion:
These data demonstrate that oxidant stress increases SMAD3 activity and SMAD3-dependent upregulation of PAI-1 through a mechanism involving redox regulation of NEDD9. Identifying prothrombotic control of SMAD3 by NEDD9 may have important therapeutic implications for CTEPH.
Abstract 12959: Association of Gender-Affirming Hormone Treatment With Metabolic Syndrome in Transgender Patients Compared With Cis-Gender Patients
Authors: Marijic Buljubasic Andriana , Goodman Michael , Budoff Matthew J , Gornbein Jeffrey , Hashemi Leila
Published: December 2023

Background:
The long-term effects of gender-affirming hormone therapy (GAHT) is an area of priority in transgender (TG) health research. Also, there is a great gap in our understanding of sex hormone and sex chromosomes and their role in Metabolic Syndrome (MetS) and therefore atherosclerosis risk.

Hypothesis:
sex hormones, (estradiol and Testosterone) affect the development of MetS and therefore heart disease.

Methods:
Using International Classification of Diseases ninth and tenth codes for gender dysphoria from the Veteran Health Affairs national data, we identified 284 transfeminine (TF) and 79 transmasculine (TM) patients with documented
received GAHT initiation date
(index date=ID) and MetS components data. GAHT consists of estradiol in TF and testosterone in TM individuals.TG individuals were matched to 252 cis-male (CM) and 111 cis-female (CF) referents. MetS z-scores were calculated as: where . In the longitudinal analyses, time (years) was computed from the ID (“Time 0”) with negative and positive values indicating pre- and post ID period, respectively. The mean MetS z-scores were compared among TG and cis-gender groups over time using a repeated measures analysis of variance model.

Results:
The mean age of cohort was 41, 84% non-Hispanic White and 9% non-Hispanic Black.Table 1 shows MetS z-score significantly changed overtime (p<0.001) and differed across groups (p<0.05). Fig 1 shows the changes in adjusted (year and group) MetS z-scores with locally estimated scatterplot smoothing curves. The data indicate that estrogen and testosterone may have different effects on metabolic status. hormones

Conclusion:
Sex hormones play an important role in the MetS development sex difference.
Abstract 12968: Atorvastatin for the Treatment of Endocardial Fibroelastosis Formation in a Preclinical Animal Model
Authors: Gierlinger Gregor , Rech Lavinia , Koutsogiannaki Sophia , Emani Sitaram M , Del Nido Pedro J , Friehs Ingeborg
Published: December 2023

Background:
Endocardial fibroelastosis (EFE) frequently associated with development of HLHS or critical AS, restricting growth of the left ventricle (LV). The mechanism of EFE formation is the transition from endocardial endothelial cells to mesenchymal cells (EndMT). Regulation of EndMT in cardiac fibrosis is mainly through the TGF-β pathway, and upregulated Krüppel-like factor 2 (KLF2) inhibits the TGF-ß pathway by blocking SMAD2/3. Besides their plasma lipid-lowering effect, statins (e.g. Atorvastatin) directly upregulate KLF2 and are thereby atheroprotective (i.e., inhibit EndMT). The aim was to evaluate whether the upregulation of KLF2 with Atorvastatin inhibits EFE formation.

Methods:
Heterotopic rat heart transplantation was performed using 2-4 day-old donor hearts into adolescent recipients, which induces LV EFE growth. Atorvastatin (n=7) was administered daily at 3 mg/kg intraperitoneally for two weeks and compared to untreated/vehicle (n=5) controls. At postoperative day 14, LV EFE thickness was determined on Masson’s trichrome-stained slides. Gene expression of KLF2 was analyzed by qRT-PCR and protein expression by Westernblot and quantified via densitometry for SMAD2/3 and collagen.

Results:
Mean LV EFE thickness was significantly decreased in the Atorvastatin group (22.3±2.5μm) compared to 176.8±22.6μm in the untreated/vehicle-treated group (p<0.0001,
A
). KLF2 was significantly upregulated in Atorvastatin treated hearts (p=0.0173,
B
). SMAD2/3 and collagen were significantly elevated in the control group, p=0.0014 and p=0.048, respectively (
C, D
).

Conclusion:
LV growth restriction through EFE formation precludes patients from biventricular repair. Until now, surgical resection has been the only available therapeutic option. With this study, we show that Atorvastatin impedes EFE formation within the LV cavity in neonatal rat hearts through the upregulation of KLF2. Atorvastatin is, therefore a promising therapeutic agent.
Abstract 12972: Trained Innate Immunity Through Toll-Like Receptor 4/Interferon Signaling Establishes Cardioprotection in a Stress-Induced Cardiomyopathy Model
Authors: Lim Kenji Rowel Q , Hayashi Tomohiro , Tiwary Sajal K , Kovacs Attila , Diwan Abhinav , Mann Douglas L
Published: December 2023

Introduction:
Although extensively studied, the mechanisms responsible for the development of cardioprotection following preconditioning stimuli are not known. Our group showed that isoproterenol (ISO) mediated cardiac injury induces potent cardioprotection against a second ISO challenge for up to 5 weeks. The lack of an immune response after the second ISO dose and the durability of protection suggested that trained innate immunity might represent a novel mechanism for cardioprotection.

Hypothesis:
We hypothesized that ISO confers cardioprotection through trained immunity via Toll-like receptor 4 (TLR4) signaling that is activated by damage-associated molecular patterns released by ISO-induced cell necrosis.

Methods:
Wild-type C57BL/6J mice were intraperitoneally injected with TLR agonists or diluent (saline), and then 300 mg/kg ISO a week later. Mice were assessed before and after receiving ISO via serum cardiac troponin analysis, flow cytometry, and 2-D echocardiography.

Results:
The TLR4 agonist lipopolysaccharide (LPS), but not TLR1/2 or TLR3 agonists, induced cardioprotection as shown by decreased troponin I release (p<0.01), reduced cardiac neutrophil influx (p<0.05), and decreased left ventricle wall motion abnormalities (p<0.05) following ISO injury compared to saline treated controls . RNA sequencing identified interferon signaling as commonly upregulated (p<0.05) in mouse hearts a week after LPS or ISO pre-treatment. Blocking type I/II interferon receptors partially abolished LPS-induced cardioprotection, while pre-treatment with recombinant interferon β+γ conferred cardioprotection as shown by decreased troponin I release post-ISO (p<0.01). Given that β-glucan reverses the epigenetic tolerizing effects of LPS in immune cells, we treated mice with β-glucan following LPS pre-treatment and observed that the cardioprotection to ISO was abolished.

Conclusions:
Viewed together this study shows for the first time that TLR4/interferon signaling confers cardioprotection against ISO-induced injury. Our findings further suggest that this cardioprotective response may be secondary to TLR4 mediated epigenetic changes that dampen immune responses following tissue injury, consistent with trained innate immunity.
Abstract 12975: Metabolic Reprogramming in Adult Cardiomyocytes Promotes Heart Regeneration
Authors: Hsieh Patrick C
Published: December 2023

Cardiac regeneration after injury is limited by the low proliferative capacity of adult mammalian cardiomyocytes. However, certain animals readily regenerate lost myocardium through a process involving dedifferentiation, which unlocks their proliferative capacities. We tested if dedifferentiating or reprogramming adult cardiomyocytes may recover their proliferative capability and thus promote heart regeneration after injury in mice.We bred mice with inducible, cardiac specific expression of the Yamanaka OSKM factors, enabling adult cardiomyocyte reprogramming and dedifferentiation in vivo. Two days after OSKM induction, adult cardiomyocytes presented a dedifferentiated phenotype and increased proliferation in vivo. Microarray analysis revealed that upregulation of ketogenesis was central to this process. Adeno-associated virus-driven HMGCS2 overexpression induced ketogenesis in adult cardiomyocytes and recapitulated cardiomyocyte dedifferentiation and proliferation observed during partial reprogramming. This same phenomenon was found to occur after myocardial infarction, specifically in the border zone tissue, and HMGCS2 knockout mice showed impaired cardiac function and response to injury. Finally, we showed that exogenous HMGCS2 rescues cardiac function after ischemic injury. Our data demonstrate the importance of HMGCS2-induced ketogenesis as a means to regulate metabolic response to cardiomyocyte injury, thus allowing cell dedifferentiation and proliferation as a regenerative response. (Cheng
et al
.
Circulation
2022).
Abstract 12993: Higher Risk of Heart Failure in Patients With Sickle Cell Disease
Authors: Henry Terrence , Eun Yong , Ayinla Raji
Published: December 2023

Background:
Sickle cell disease (SCD) is a known risk factor for the development of cardiovascular disease. Congestive heart failure (CHF) is a major cardiovascular complication in patients with SCD. A high-output cardiac state and increased systemic vascular resistance in SCD patients lead to ventricular hypertrophy and diastolic dysfunction. The subject of this study is to examine the risk of developing CHF in SCD when compared to patients without SCD using the All of Us Database.

Methods:
We conducted a propensity score matching (PSM) analysis to evaluate the effect of sickle cell disease (SCD) on the risk of developing congestive heart failure (CHF) in a cohort of 287,012 American individuals enrolled in the All of Us database. Covariates for matching included age, gender, race, ethnicity, income level, education level, marital status, cigarette exposure, alcohol exposure, drug exposure, and comorbidities. The resulting control group (n=761) was matched to the SCD patient group (n=761) based on propensity scores. A logistic regression analysis was then conducted to determine the association between SCD and CHF, adjusting for significant factors.

Results:
The logistic regression analysis revealed a significant association between SCD and CHF. In the unadjusted model, SCD patients had an odds ratio (OR) of 1.42 (95% CI: 1.09-1.84, p=0.009) for developing CHF compared to the control group. After adjusting for age group, income, marital status, drug exposure, and modified Charlson comorbidity index, the adjusted OR was 1.60 (95% CI: 1.20-2.15, p=0.002).

Conclusion:
Patients with SCD had an increased risk of developing CHF, compared to propensity score-matched controls.
Abstract 13007: Ketone Bodies for Right Ventricular Failure: A Unique Therapeutic Opportunity
Authors: Blake Madelyn , Puchalska Patricia , Kazmirczak Felipe , Thenappan Thenappan , Crawford Peter , Prins Kurt W
Published: December 2023

Introduction:
Right ventricular failure (RVF) is the leading cause of death in pulmonary arterial hypertension (PAH), but effective therapies for RVF are lacking. Ketones exert therapeutic effects through suppression of the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome and exhibit favorable metabolic properties in LVF. However, the relationships among serum ketone bodies, RV inflammasome activation, and RV function in preclinical and human RVF are unexplored.

Hypothesis:
Serum ketones correlate with RV function and induction of therapeutic ketosis ameliorates RV dysfunction.

Methods:
51 PAH patients were dichotomized into preserved or impaired RV function based on a cardiac index of 2.2 L/min/m
2
. Serum ketone bodies acetoacetate (AcAc) and β-hydroxybutyrate (BOHB) were quantified using ultra performance liquid chromatography and mass spectrometry. The relationships between AcAc and BOHB and clinical measures of RV function were evaluated. In rodent studies, male Sprague Dawley rats were assigned to three groups: control (saline injection), monocrotaline (MCT) standard chow diet (MCT-SD), and MCT ketogenic diet (MCT-KD). Immunoblots and confocal microscopy probed macrophage NLRP3 activation in RV extracts and sections. RV fibrosis was determined by Picrosirus Red. Echocardiography evaluated RV function.

Results:
Human RVF patients lacked a compensatory ketosis as serum AcAc and BOHB levels were not associated with hemodynamic or echocardiographic measures of RV function. In rodent studies, AcAc and BOHB levels were also not elevated in MCT-mediated RVF, but the ketogenic diet significantly increased AcAc and BOHB levels. MCT-KD exhibited suppressed NLRP3 activation with a reduction in NLRP3, ASC (apoptosis-associated speck-like protein), pro-caspase-1, and interleukin-1 beta on immunoblots. Moreover, the number of ASC-positive macrophage in RV sections was reduced, RV fibrosis was blunted, and RV function was augmented in MCT-KD rats.

Conclusions:
Our preclinical and clinical data suggests therapeutic ketosis could combat RVF, and patients with RVF are uniquely primed for ketogenic interventions due to a lack of effective ketosis.