bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12687: Race, Resilience, and Health Literacy Are Important to Medication Adherence in Those With Heart Failure
Authors: Meraz Rebecca , McGee Jocelyn , Perry Elizabeth , Ke Weiming , Osteen Kathryn A
Published: June 2023

Background:
Personal and psychological factors, such as depression, have a considerable influence on nonadherence to medications and self-care in those with heart failure. More evidence, however, is needed about positive personal factors that motivate adherence to medications and self-care in those with heart failure. Objective: The purpose of this study was to investigate whether there was a consistent and predictable relationship between the personal resources of resilience, hope, health literacy, social support, and self-care activation and adherence to medications and HF self-care and whether race impacts adherence.

Methods:
This study used a prospective, cross-sectional design. Correlation and multiple regression analyses were used to estimate associations between study variables. A nationwide, diverse sample was recruited for this study.

Results:
Of the 174 participants, 51% were female, 48% were persons of color (POC) and the mean age was 62 years. Medication adherence and health literacy were significantly lower among POC compared to Whites. POC were more likely to be under 65 years, single, and have a lower income. Following adjustment for differences in age and depressive symptoms, a predictive relationship remained between resilience (B = -0.049, p < 0.001), health literacy (B = -0.258, p = 0.003) and medication adherence. A high level of perceived social support (B = 5.359, p < 0.001) was a predictor of better HF self-care.

Conclusion:
Persons with heart failure may have better medication adherence and overall self-care if sufficiently resilient, health literate, and supported regardless of their degree of hope or activation. Race and age may be important factors to consider. More research is needed to understand the relationship between resilience and medication adherence.
Abstract 12689: Electron Transport Chain Inhibition to Decrease Reperfusion Injury in Transplanted Donation After Circulatory Death Rat Hearts
Authors: Quader Mohammed , Chen Qun , Akande Oluwatoyin E , Cholyway Renee , Mezzaroma Eleonora , Lesnefsky Edward J , Toldo Stefano
Published: June 2023

Introduction:
Intrinsic to the donation after circulatory death (DCD) donation is ischemia and reperfusion injury, primarily mediated through release of reactive oxygen species (ROS) from the damaged mitochondria. Amobarbital (AMO) is a transient, reversible inhibitor of complex I known to decrease ROS generation. We studied whether AMO treatment during reperfusion can improve function in transplanted DCD hearts.

Methods:
Sprague Dawley rats, were assigned to four heart donor groups- DCD or DCD+AMO and control beating-heart donor (CBD) or CBD+AMO (n=6-8 each). Donor rats were anesthetized using ketamine/xylazine, intubated and connected to a ventilator. The carotid access was used to deliver heparin (1000 U/kg) and vecuronium bromide (4 mg/kg) to paralyze diaphragmatic muscles. The DCD process was initiated by disconnecting the ventilator. Donor hearts were procured following 25 minutes of
in-vivo
ischemia in the DCD groups, while CBD hearts were procured without terminating the ventilation. At procurement, after clamping the aortic arch, all donor hearts received 10 ml of University of Wisconsin cardioplegia solution delivered through the carotid cannula. The CBD+AMO and DCD+AMO groups received AMO (2 mM), dissolved in the cardioplegia. Heterotopic heart transplantation was performed in recipient rat’s abdomen. After 14 days the transplanted heart function was measured with a balloon tip catheter.

Results:
Compared to CBD hearts, DCD hearts had significantly lower developed pressure, the rate pressure product (developed pressure times heart rate), and negative dP/dt indicating decreased contractile and impaired diastolic function (Figure). AMO treatment of the DCD hearts resulted in significantly improved cardiac function compared to the untreated DCD hearts.

Conclusions:
A single treatment with AMO during the heart procurement improves the transplanted DCD heart function which was comparable to the control CBD hearts.
Abstract 12700: Post-GWAS Functional SNP Analysis to Define Genetic and Acquired Pathogenesis of Pulmonary Arterial Hypertension
Authors: Sun Wei , Jiang Danli , Li Gang , Chan Stephen Y
Published: June 2023

Introduction:
Pulmonary arterial hypertension (PAH) is an enigmatic and morbid disease where insights are emerging regarding genetic susceptibility. Genome-wide Association Studies (GWAS) have identified genomic SNPs associated with increased PAH risk. It has been challenging to define the mechanisms underlying the contribution of non-coding PAH-associated functional SNPs (fSNPs) to the pathogenesis of this disease.

Methods:
We developed a post-GWAS functional genomics strategy to define the causative fSNPs and the associated biological mechanisms. It includes Reel-seq (Regulatory element-sequencing), an EMSA-based technique to identify fSNPs in a synthetic SNP library; SDCP-MS (SNP-specific DNA competition pulldown-mass spectrometry) to identify proteins that specifically bind to fSNPs; and AIDP-Wb (allele-imbalanced DNA pulldown-Western blot) to show allele-imbalanced binding of these proteins to fSNPs. The regulation of risk gene expression by fSNP-binding proteins and their pathogenicity were determined in human pulmonary arterial endothelial cells (PAECs) and confirmed in PAH animal models and patients.

Results:
An intergenic SNP rs4738801 was identified as a fSNP by Reel-seq. This non-coding fSNP resides in a remote upstream enhancer region of SOX17, an endothelial effector increasingly associated with PAH pathogenesis. Using SDCP-MS and AIDP-Wb, we found that transcription factor FUBP1 binds to rs4738801 risk allele C with lower affinity than non-risk allele G, resulting in a decrease in SOX17 expression. FUBP1 and target gene SOX17 controlled PAH-associated pathophenotypes in PAECs, including proliferation, apoptosis, and angiogenesis. Downregulated by major acquired PAH trigger hypoxia, FUBP1 and SOX17 were decreased in lungs and pulmonary ECs isolated from PAH patients and mouse models. A 3.8-fold enrichment of risk allele C was found in patients with PAH induced by hypoxia, but not in PAH associated with connective tissue disease or other etiology.

CONCLUSION:
Our functional genomics findings identify a novel role of FUBP1 in the functional regulation of SOX17 locus and elucidate a pathogenic mechanism that combines the acquired PAH-triggering factors and altered genetic susceptibility.
Abstract 12709: Characterization of Growth Hormone Releasing Hormone Receptor During Cardiomyogenesis
Authors: Wanschel Amarylis , Chatzistergos Konstantinos , Salerno Alessandro , Valasaki Krystalenia , Kurtenbach Stefan , Balkan Wayne , Dykxhoorn Derek , Schally Andrew , Hare Joshua M
Published: June 2023

Introduction:
Differentiation and expansion of cardiomyocytes from human-induced pluripotent stem cells is a poorly understood process, and the signals promoting differentiation of cardiomyocytes toward specific cell fates are not well defined. Here we show that the growth hormone-releasing hormone receptor (GHRH-R) signaling pathway controls this differentiation process and cell fate.

Hypothesis:
Stimulation of hPSCs with GHRH promotes β-catenin stabilization through the GH/IGF1 axis. The presence of cell-surface GHRH-R differentiates between atrio-ventricular cardiomyocytes and non-cardiomyogenic cardiac cells, including coronary vascular, neuronal and pacemaker cells, such that selecting for GHRH-R allows for the elimination of pacemaker cells and derivation of a pure population of atrio-ventricular cardiomyocytes.

Methods:
Using RNA-seq to comprehensively characterize the GHRH-R signaling pathway, we identified that NKX2-5, a transcription factor involved in progenitor specification and differentiation into atrio-ventricular cardiomyocytes, is upregulated in response to GHRH.

Results:
GHRH-R signaling also upregulated HIF-1α via the PI3k/Akt/mTOR pathway to enhance NKX2-5 transcription and stimulate a Warburg-like effect in developing cardiomyocytes.

Conclusions:
Together these findings provide crucial insights into human stem cell differentiation and offer a translationally useful tool to optimize the development of pure cardiomyocyte preparations derived from induced pluripotent stem cells.
Abstract 12717: Understanding and Addressing the Unique Challenges of Heart Failure Management in Older Adults
Authors: D'Anna Susan , Emmons Margaret , Cantlin Deborah , Mujtaba Mohammadtokir , Gilstrap Lauren
Published: June 2023

Introduction:
The heart failure (HF) population is aging. As patients age, certain aspects of HF care become more and less challenging. The aim of this qualitative study is to understand which aspects of HF care are the most challenging for older adults and identify potential solutions and coping strategies.

Methods:
We conducted semi-structured interviews with 41 patients ≥75 years old with HF. The oldest was 93 years old and the youngest was 75 with an average age of 82. Interviews were conducted in both the inpatient (n=23) and outpatient/clinic (n=18) settings. Patients were asked a series of 3 questions focused on care challenges, effective strategies and coping mechanisms. Interviews were recorded and transcribed. Recordings were listened to while reviewing the transcripts, then analyzed and coded for thematic analysis.

Results:
Older patients with HF identified: “salt/fluid restrictions,” “exercise limitations,” “medication compliance” and “transportation for visits” as key challenges of HF management. Effective strategies identified included: “family support,” “pill boxes and logbooks to help me remember” and “the socialization of cardiac rehab.” Successful coping strategies included: “family,” “religion” and “motivation to maintain independence.”

Discussion:
Older patients with HF face many of the same challenges as younger patients but also face additional hardships with transportation, cognitive limitations and social isolation (
Figure 1
). These challenges are worse for older adults without family support. A desire to remain independent is a significant motivating factor for older adults with HF. Understanding these challenges and motivations can inform care plans better tailored to the care of older adults with HF.
Abstract 12720: Hypertension in the Dominican Population Living in the United States Enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Compared to Dominicans Living in the Dominican Republic: Understanding the Impact of Risk Factors
Authors: Alvarez Luisa , April-Sanders Ayana K , Lee Un Jung , herrera cesar , Collado Donaldo , Kaplan Robert , Gonzalez Franklyn , Daviglus Martha L , Garcia Olga , Elfassy Tali , Schneiderman Neil , Perreira Krista , Aviles-Santa Larissa , Talavera Gregory A , Corsino Leonor , Rodriguez Carlos
Published: June 2023

Background:
Hispanics/Latinos of Dominican heritage living in the United States (US) have the highest prevalence of hypertension (HTN) compared with other Hispanic/Latino groups. To better understand cardiovascular health among Dominicans, a primarily immigrant population, it is crucial to examine the unique social contexts that influence their health outcomes. Our objective was to evaluate HTN prevalence and risk factors among individuals of Dominican descent from two social contexts - the US and the Dominican Republic (DR).

Methods:
HTN among DR Dominicans (DRD) was assessed using data from ENPREFAR-HAS 17, a representative sample of DRD (N=2,016; mean age 40±0.37 years, 60% females, unweighted); while HTN among US Dominicans (USD) was assessed from the HCHS/SOL, a population-based cohort study of Hispanics/Latinos in the US (Dominican subset, N=1,473; mean age 41±.25 years, 50% females, weighted). HTN was defined as blood pressure recording ≥140/90 mm Hg, self-reported HTN, or HTN treatment. Exposures included sociodemographic, lifestyle, and clinical characteristics. Poisson regression analyses were used to estimate associations between study characteristics and the prevalence of HTN (PR = prevalence ratio), adjusting for age and gender.

Results:
HTN was more prevalent among DRD (31%) than USD (27%). Younger adults (18-39) and females were more likely to have HTN in the DR, while older adults (40-60+) and males had a higher prevalence of HTN in the US. In those with HTN, awareness was common (74% USD, 68% DRD); most were receiving treatment (62% USD, 61% DRD), but overall, HTN control was low (35% USD, 36% DRD). Alcohol use was inversely associated with HTN prevalence for DRD (PR=0.8) with no association among USD. In both settings, diabetes (PR
DRD
= 1.4; PR
USD
= 1.4) and increased BMI (PR
DRD
= 1.8; PR
USD
= 2.0) were associated with a greater prevalence of HTN. Conversely, physical activity was protective against prevalent HTN among USD (PR=0.80) but associated with increased prevalence of HTN among DRD (PR=1.16); all p<0.05.

Conclusions:
Variations in social, lifestyle, and clinical characteristics associated with HTN among Dominicans in the US and DR were identified, suggesting that context and cultural issues matters among immigrant populations.
Abstract 12727: Ultrafiltration for Decompensated Heart Failure Using Aquadex® Without Heparin
Authors: Leonard Kristina , Gupta Ritika , Patalinghug Paul , Berthiaume Kyrah , Mitchel Hayley , Matushinec Sarah , Gopalan Radha
Published: June 2023

Introduction:
Anticoagulation therapy is necessary during ultrafiltration (UF) to prevent thrombus formation during the filtering process. Heparin is the anticoagulating agent recommended by Aquadex®. However, many patients are already within a therapeutic INR range due to warfarin anticoagulation. Here we present a unique case of Aquadex® UF without the use of heparin anticoagulation.

Case Presentation:
An 87-year-old male with a history of LVAD implant experienced 2 weeks of weight gain and dyspnea on exertion and at rest due to fluid retention despite GDMT and escalation of oral diuretics. On admission, physical exam revealed elevated JVP, ascites, and 3+ bilateral lower extremity pitting edema and 32 pounds weight gain. He was on a home dose of warfarin per LVAD protocol. Investigations revealed INR 2.9, HCT 29.6, BUN 58, and Cr 2.05. Aquadex® UF was initiated with a therapeutic INR range of 2-3. The patient tolerated UF well without complication and was transitioned back to oral diuretics after 4 days of UF, 24 pounds of weight loss, and 7 liters of fluid removal. He was stable at discharge, but was readmitted two weeks later with identical symptoms and INR 1.9, HCT 26, BUN 32, and Cr 1.69. Aquadex® UF was again initiated with a therapeutic INR range 1.5-2. He again tolerated UF well without complication for 4 days, lost 28 pounds, and had 8.9 liters of fluid removed on this second admission. Aquadex® fluid removal during both hospitalizations is depicted in Figure 1.

Conclusions:
Our case supports the utilization of UF without the use of heparinization on patients who are already anticoagulated with warfarin. Further, successful UF without clotting complications is possible in INR ranges between 1.5-2 and 2-3 as evidenced during the two hospitalizations.

Figure 1.
INR levels were maintained within therapeutic ranges using warfarin anticoagulation during Aquadex® UF.
Abstract 12730: Comparisons of Health Outcomes Between Baby Boomers and Silent Generation Among Older Adults With Heart Failure
Authors: Wu Jiarong , Latimer Abigail , Lin Chin-Yen , Moser Debra K
Published: June 2023

Background:
Heart failure (HF) is a clinical syndrome of aging. Many studies compare older (≥65 years) and younger (< 65 years) participants’ HF experiences as younger patients’ HF etiology and psychobehavioral factors are distinct from older patients. Yet, best practice geriatric HF management necessitates understanding of the differences present among older generations.

Objective:
To compare health outcomes (cardiac event-free survival and quality of life [QoL]) in older adults with HF by generational cohort including baby boomers and silent generation.
Method:
This 2-year longitudinal study of 497 patients with HF (male 61%, age 65±9 years, NYHA III/IV: 34%) included cardiac event data (i.e., HF readmission and cardiac death) collected from patient interview, hospital database and death certificate. QoL was measured using the Minnesota Living with Heart Failure. We collected demographic (e.g., gender, race), clinical (e.g., comorbidities), and psychobehavioral (e.g., depressive symptoms, anxiety, HF knowledge, self-care) factors as covariates. We conducted Chi-squares, t-tests, linear and Cox regression for data analysis.

Results:
Two fifths of the participants (39.63%) were baby boomers. Baby boomers had more depressive symptoms, higher levels of anxiety, lower levels of B-type natriuretic peptide, and higher number living in the same house than those in the silent generation (all
P
<.05). Lower percentages of baby boomers were Whites and unemployed compared to the silent generation cohort (
P
<.05). There were no differences in other covariates between the two cohorts. Baby boomers had significantly worse QoL than patients in the silent generation (
P
<.001). Before and after adjusting for covariates, generation cohort was a significant predictor of cardiac event-free survival (HR=1.46-1.47, both
P
<.05).

Conclusion:
Baby boomers with HF had better cardiac event-free survival, but more depressive symptoms, higher levels of anxiety, and worse QoL compared to older adults in the silent generation. In the US, baby boomers are the largest generational cohort in 2022 and are approaching their late 50s and mid-70s. As this group continues to age with increasing rates of HF, practice and research will benefit from continued focus on their needs.
Abstract 12731: Implementation Barriers of Class 1a Heart Failure Guideline Recommendations in Developing Countries
Authors: Guilliod Christian R , Blumer Vanessa
Published: June 2023

Introduction:
In April 2022, the American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Failure Society of America (HFSA) released an updated guideline for the management of heart failure (HF). The degree to which these guideline recommendations can be broadly implemented in resource-limited settings, including some developing countries, has not been described.

Methods:
The 2022 AHA/ACC/HFSA HF guidelines were reviewed and Class 1A recommendations were analyzed for potential implementation barriers in developing countries. For this analysis, Venezuela was used as a case example. Implementation barriers were analyzed on a Likert-type scale from “not a barrier” to “extreme barrier”. Among recommendations with moderate to extreme implementation barriers, potential limiting factors were specified.

Results:
A total of twenty-two Class 1A HF recommendations were analyzed for potential implementation barriers. Among them, 8 (36%) were classified as “not a barrier”, 3 (14%) as “somewhat of a barrier”, 5 (23%) as “moderate barrier”, and 6 (27%) as “extreme barrier”. Regarding limiting factors, 10 (50%) were related to non-availably of therapeutic drugs/interventions, 4 (20%) involved high incurring costs, and 6 (30%) were related to lack of formal training in HF and/or multidisciplinary specialized care (Figure).

Conclusions:
There are potential implementation barriers to Class 1A recommendations made in the 2022 AHA/ACC/HFSA HF guidelines in resource limited settings, particularly in certain developing countries where availability and costs of interventions, and lack of formal HF training, represent important limiting factors. Further endeavors should encourage guideline-based recommendations to address resource-limited settings and efforts should be made to maximize implementation around the world.
Abstract 12732: Cardiac Sarcoidosis With Elevated Cardiac Troponin Mimicking Acute Myocardial Ischemia
Authors: Casipit Bruce , Al Sudani Hussein , Amanullah Aman M
Published: June 2023

Background
Cardiac Sarcoidosis (CS) is a disease with variable presentation causing significant morbidity and mortality. Concurrent signs of myocardial injury as evidenced by troponin elevation add to the complexity of an already challenging diagnosis.

Case
A 48-year-old female with no significant past medical history presented with episodes of presyncope for 2 months. ECG showed a bifascicular block. Troponin I was elevated to 7.29 ng/mL. 2D echo showed Left Ventricular (LV) systolic dysfunction with an LVEF of 40%. Heparin drip was initiated for a possible NSTEMI. Coronary angiography showed no evidence of epicardial coronary artery disease but showed an anomalous right coronary artery which on CT angiogram later showed no hemodynamically significant stenosis. Telemetry monitoring captured intermittent complete atrioventricular blocks. A biventricular implantable cardioverter-defibrillator was inserted. Due to concerns for infiltrative cardiac disease, a cardiac magnetic resonance (CMR) was done showing findings consistent with cardiac sarcoidosis (CS). CT scan of the chest showed radiographic evidence of pulmonary sarcoidosis, however, she declined further invasive workup. She was then started on systemic corticosteroids. 2D echo 6 months later revealed improvement in the LVEF to 55%.

Discussion
Our case encompasses the variable presentation of CS including cardiac conduction abnormalities and LV systolic dysfunction. Concomitant troponin elevation in CS can mimic myocardial ischemia making the diagnosis more challenging. This highlights the importance of appropriate diagnostic acumen in approaching a case like this. Current guidelines now include non-invasive means for diagnosis including the use of CMR/PET CT, especially since endomyocardial biopsy has a low sensitivity. Treatment strategies aim to mitigate the long-term effects of CS on the heart, however, there is a paucity of data for appropriate pharmacological regimen.
Abstract 12737: Baseline Carotid Sinus Massage in the Supine Position Predicts Outcome of Head Up Tilt Table Testing: Potential for Abbreviating the Tilt Table Test Protocol
Authors: Prakash Atul , Truong Julie , Nathans Milana
Published: June 2023

Introduction:
Carotid sinus massage (CSM) has been used to evaluate carotid sinus hypersensitivity. Its role in evaluating a vasodepressor response has not been well studied. CSM can also result in a vasodepressor response in the absence of significant bradycardia. Its role in predicting the subsequent outcome of head-up tilt testing (HUT) is not well defined.

Hypothesis:
A vasodepressor response elicited with baseline carotid sinus massage (CSM) may predict the subsequent outcome of HUT.

Methods:
In this prospective study Consecutive patients with a history suggestive of a reflex neurocardiogenic etiology underwent HUT. Patients underwent HUT testing using a standard protocol, including baseline CSM in the supine posture followed by HUT testing at 60 degrees for 30 minutes. If negative, a repeat of CSM was performed in the upright posture. Then, isoproterenol was infused in incremental dose 1 to 3 mcg/minute.

Results:
25 patients (20 females and 5 males) with a mean age of 52.87±6.77 years underwent HUT. 5 out of 25 (20%) patients had a positive tilt result for a vasodepressor response. 4 of these 5 patients had a significant vasodepressor response (symptomatic hypotension BP drop less than 30 mmHg) without significant bradycardia (HR less than 50 BPM) during CSM in the supine posture. Of these patients, 3 patients became positive during HUT and 1 patient became positive during isoproterenol infusion. The positive predictive value was 0.8. Sensitivity was 67%. 20 out of 25 (80%) patients had a negative tilt result for a vasodepressor response despite protocol completion. 18 of these 20 patients had no drop in BP during CSM and no significant bradycardia. The negative predictive value was 0.9. The specificity was 94.74%. 2 of these patients had a negative response on CSM but a borderline response at HUT with borderline symptoms with the isoproterenol. These 2 had a transient drop in BP when CSM was repeated at the end of 30 minutes during the head-up position.

Conclusions:
In this population of patients, a negative CSM in the supine posture predicted a subsequent negative Tilt test. Baseline CSM can be performed at the bedside and may obviate the need for full tilt table testing even for patients with a clinical diagnosis of reflex syncope (vasodepressor).
Abstract 12755: Role of Micriobiome-Derived Short-Chain Fatty Acid Butyrate in Pulmonary Hypertension
Authors: Pulgarin Andres , Methe Barbara , Morris Alison , Al Ghouleh Imad
Published: June 2023

Introduction:
Pulmonary hypertension (PH) is a progressive, severe disease characterized by high blood pressure in the pulmonary circulation, inflammatory cells infiltration and excessive pulmonary vascular remodeling. Endothelial cell (EC) dysfunction is increasingly recognized as a precipitating event for this remodeling. Butyrate, a microbiome-derived molecule with histone deacetylation activity and present in circulating blood, has been associated with benefit in atherosclerosis and associated cardiovascular diseases. Due to a dearth of knowledge on the role of microbiome-derived molecules in PH-EC, we aimed to test whether butyrate plays a protective role in EC under PH.

Results:
Mice supplementation with butyrate (sodium butyrate, NaB) attenuated hypoxia-induced right ventricular (RV) pressure (43±2 to 35±3 mmHg, p<0.05) and RV hypertrophy (RV/LV+Septum= 0.43±0.008 to 0.38±0.01, p<0.05) in vivo. NaB also lowered hypoxia-induced circulating monocyte numbers and reduced gene expression of inflammatory adhesion molecule VCAM-1 in hypoxic lung-derived CD31+ ECs, as well as increased expression of ERM binding Phosphoprotein 50 (EBP50), a protein we have shown to modulate endothelial reprogramming in PH. In vitro, NaB attenuated PH-related inflammatory cytokine IL1β-induced human pulmonary arterial EC (HPAEC) migration at 48 h. Consistently, NaB also reversed IL1β-induced increase in VCAM-1 expression at the mRNA and protein level in HPAEC. Moreover, NaB rescued the expression of IL1β-induced reduction in cell surface protein integrin α3, EBP50, and Vangl2 (Van Gogh-like) protein, a member of planar cell polarity core whose downregulation has been linked to PH.

Conclusions:
Collectively our results demonstrate that butyrate attenuates PH potentially via protecting against myeloid cell induction and pathophysiological proinflammatory, promigratory pulmonary vascular EC activation. Butyrate may also reduce EC reprogramming through its effects on EBP50, and may promote pulmonary vascular homeostasis through Vangl2 induction. These findings support the potential for therapeutic benefits of butyrate in PH and the need for further investigation of the role of microbiome-derived metabolites in this devastating disease.
Abstract 12766: Tropsensor: A Rapid Non-Invasive Transdermal Solution For Troponin Measurement
Authors: Titus Jitto , Wu Alan H , Biswal Siddharth , Burman Atandra , Jaffe Allan S
Published: June 2023

Introduction:
Early identification of Acute Myocardial Injury can prompt rapid triage and appropriate interventions to improve clinical outcomes. Over 10 million patients present at the ED with chest-pain, with the majority due to non-cardiac causes, resulting in unnecessary burdens for Emergency Departments (ED). An instant non-invasive method to measure cardiac troponin (cTn) would therefore be of great benefit.

Identified need:
All Guidelines recommend the use of high sensitivity (HS) cTn for the diagnosis of acute coronary syndromes (ACS). Current biochemical biomarker testing relies on labeling the cTn with turnaround times often an hour or more. Point-of-care solutions reduce the test time, but still depend on the proper handling of samples and blood processing techniques that could lead to difficulties. Tropsensor provides a non-invasive alternative to standard of care (SOC) hs-cTn measurements without the need for a blood draw. The molecular infrared spectroscopy-based transdermal device provides a cTn readout within 5 minutes and allows for serial measurements without any of the delays or complications of blood draws.

Methods:
A 26-patient (consented and IRB approved) study was conducted at Zuckerberg San Francisco General Hospital with recruitment based on ACS-related presenting symptoms at the ED. Wrist-worn Tropsensor was used on the patients while the corresponding troponin was determined using a high sensitivity (SOC) assay (Siemens ADVIA Centaur) via a blood draw.

Results and conclusions:
A Pearson’s correlation of 82% with the hs-cTnI was observed. AMI diagnosis sensitivity was 100%, Specificity=50%, PPV=81.8%, NPV=100% and accuracy=84.6%. The Tropsensor modality seems to provide data similar to that of a hs-cTn assay. If so, it would accelerate the assessment of patients presenting with chest pain. By not requiring a blood draw, the Tropsensor could provide a rapid, safe, standardized and reliable source for cTn while allowing bedside serial trending. It thus has the potential to streamline cardiac care workflow by ruling-out many non-cardiac patients and identifying those with high values who are at risk. Such an approach has the potential to facilitate appropriate patient triage towards early discharge of emergent treatment.
Abstract 12768: Evaluation of a Cardiovascular Research Initiative on the Research Career Development of Medical Students
Authors: Gandhi Anusha , Lawrence Jannel A , Meykler Marcella , Rosenzveig Akiva , Hameed Fariha R , Schroeder Lucia , Ulusan Sebahat , Abdul-Rahman Toufik , Andrew Awuah Wireko , Sheth Samip , Phillips-Wilson Tasha , Henry Mariana L , Gates Emily , Mares Adriana C
Published: June 2023

Background
The Cardiovascular Research Initiative (CVRI) was founded in 2021 by leaders and members of the American College of Cardiology (ACC) Medical Student Member Community (MSMC) to bring together students passionate about conducting cardiovascular research. The group comprises 62 students who worked on 7 review articles since December 2021 under the guidance of physician mentors. The CVRI also aims to develop members’ research knowledge and skills and thus held a webinar on ‘Key Steps in Conducting Systematic Reviews’ in February 2022.

Methods
Two surveys were created and distributed to members of the ACC MSMC. The surveys were used to assess the overall impact of the Research Initiative and Systematic Review Webinar on the career development of medical students and evaluate the diversity of participants and inclusiveness of the projects.

Results
From the Research Initiative author survey (n = 12), 92% of respondents identified as being from underrepresented backgrounds, had prior research experience and believe that research is a valuable part of their professional development. All respondents agreed that after participating in these research projects, they are likely to pursue research later in their careers, and 92% strongly believe that participating in the Research Initiative is a valuable experience for their research career development.

The Systematic Review Webinar feedback survey (n = 12) was completed by 30% of attendees, most of whom were in their last 2 years of medical school from 8 different countries. A total of 84% of respondents felt that the webinar improved their knowledge of performing a systematic review and 50% felt prepared to conduct a systematic review after attending. Additionally, 84% felt that the virtual nature of the webinar enhanced their research knowledge and would attend and recommend future webinars on research methods and related topics.

Conclusions
The CVRI provides students from various countries and underrepresented backgrounds with opportunities and knowledge to succeed in research through manuscript writing experience and educational webinars. With its growing number of participants, the ACC MSMC continues to cultivate cardiovascular research career development among medical students.
Abstract 12781: Trends in Remote Monitoring for Patients With Hf and Identification of Opportunities to Expand Rural Access
Authors: Gilstrap Lauren , Leggett Christopher , O'Malley James , Carlos Heather , Wong Sandra , kraft sally , Mackwood Matthew , Skinner Jonathan
Published: June 2023

Introduction:
Limited access, due to geographic and/or transportation barriers, is one of the most significant challenges to chronic disease management in rural areas. Remote monitoring is a potential solution that allows a patients’ implanted devices to be interrogated for arrhythmia and non-invasive hemodynamics without the patient travelling to clinic. The aim of this study is to describe recent trends in remote monitoring among patients with HFrEF and to identify barriers and expand access in rural areas.

Methods:
We created annual, cross-sectional cohorts of patients with HF in each year from 2013 to 2018 with approximately 5 million patients/year by requiring ≥1 inpatient or ≥2 outpatient ICD9/10 codes for HF in the 2 years prior. Remote interrogation was determined using ICD-9/10 and CPT codes. Rurality was determined using the beneficiaries’ ZIP code of residence and the Rural/Urban Commuting Areas (RUCA) classification. The outcome of interest was the number of HFrEF patients with ≥1 remote monitoring visit in each year between 2013 and 2018.

Results:
The use of remote monitoring increased 21% between 2013 and 2018 in patients with HFrEF. By 2018, 9.3% of patients had ≥1 remote monitoring event (Figure 1). After multivariable adjustment for patient factors, living in a rural area was associated with a 14% greater odds (95% CI 1.13, 1.14, p<0.001) of remote monitoring. However when hospital referral region (HRR), a geographic delineation of health care markets, was added to the model, living in an urban area became associated with a 7.8% greater odds of remote monitoring (95% CI 1.07, 1.08, p<0.001).

Conclusion:
Remote monitoring is used by approximately 10% of patients with HFrEF. The most significant driver of remote monitoring is the HRR, or health care market, that the beneficiary resides in. To increase remote monitoring for rural patients, hospitals in predominately rural HRR’s should be incentivized to expand remote monitoring services.
Abstract 12798: Plasma Ferritin, Incident Heart Failure Phenotypes, And Cardiac Dysfunction in Late Life: The Atherosclerosis Risk in Communities Study
Authors: Aboelsaad Iman A , Claggett Brian , Arthur Victoria , Dorbala Pranav , Matsushita Kuni , Lennep Brandon , Yu Bing , Lutsey Pamela L , Ndumele Chiadi E , Farag Youssef M , Shah Amil M , Buckley Leo
Published: June 2023

Introduction:
Iron deficiency affects 10% of adults aged 70 years or older and is associated with worse symptom burden and a higher risk of hospitalization in adults with heart failure (HF) with reduced ejection fraction (HFrEF) in mid-life. However, the relationships between iron deficiency and incident HF, HFrEF and HF with preserved EF (HFpEF) in late life remain incompletely understood.

Hypothesis:
Iron deficiency, as measured by lower plasma ferritin levels, is associated with an increased risk of incident HF, HFrEF, and HFpEF in older adults.

Methods:
We included 3,567 participants (mean age 75 years, 56% women and 14% Black) from the ongoing, ARIC study who had plasma ferritin measured by an aptamer assay (SomaLogic) and were free from prevalent HF and anemia (Hb <13 for men and <12 for women). The associations of log
2
-transformed plasma ferritin with adjudicated incident overall HF, HFrEF (LVEF < 50%) and HFpEF were estimated using Cox proportional hazards models. The associations of plasma ferritin with echocardiographic measures of cardiac size and function at Visit 5 were estimated with linear regression models. All models were adjusted for age, sex, race, smoking, body mass index, coronary heart disease, diabetes, hypertension, atrial fibrillation and eGFR.

Results:
Over a median 7 years of follow-up, 312 incident HF events occurred (140 HFrEF, 137 HFpEF, 51 unknown EF). Lower ferritin level was associated with a higher risk of overall HF and HFpEF, but not HFrEF (
Figure
). Lower ferritin levels associated with a higher E/e' ratio (standardized beta [95% CI]: 0.06 [0.03-0.08]; P<0.01). Plasma ferritin levels did not associate with LV mass index or measures of LV systolic function (ejection fraction, global longitudinal strain; all P > 0.05).

Conclusion:
Lower plasma ferritin levels associate with higher LV filling pressure and greater risk of incident HF, and in particular HFpEF, in late life. Iron deficiency may contribute to the pathophysiology of HF in late life.
Abstract 12809: Cirrhotic Cardiomyopathy Before Orthotropic Liver Transplantation is Associated With Major Adverse Cardiac Events at 13-Months Post Orthotropic Liver Transplantation
Authors: Ali Saad A , Arman Huseyin E , Shamseddeen Hani , Elsner Nathaniel , Johnson Sean C , Elsemesmani Hussein I , Patidar Kavish , Orman Eric , Zenisek Joseph , Frick Kyle A
Published: June 2023

Background:
Major adverse cardiac events (MACE) are a leading cause of morbidity and mortality after orthotopic liver transplantation (OLT). Cirrhotic cardiomyopathy (CCM) is relatively common and a source of MACE in patients after OLT. Initial diagnostic criteria based on transthoracic echocardiogram (TTE) were described in 2005 and revised in 2019 with echocardiographic advancements (Table 1). We sought to identify CCM related predictors of MACE at 13 months post-OLT.

Methods:
This is a retrospective study of adult patients who underwent OLT between 2009-2019. All patients had TTE’s within one year pre-OLT and one month to 13 months post-OLT. We excluded TTE’s within one-month post-OLT to reduce contributions from stress cardiomyopathy. Patients with a left ventricular ejection fraction less than 50% pre-OLT were excluded. MACE was defined as death, MI, CHF hospitalization, or cardiac arrest. Multivariable Cox regression was used to identify independent predictors of MACE.

Results:
Of 568 OLT patients screened, 131 met inclusion criteria for this study. There were 103 and 23 patients who met 2005 and 2019 criteria, respectively. During the 13 month follow up period, 42 patients had MACE. Compared to those without MACE, patients with MACE had more ascites (93 vs 70%, p 0.003), hepatorenal syndrome (HRS) (17 vs 4%, p 0.019), delayed OLT >10 days after admission (19 vs 7%, p 0.033), pre-OLT CCM per 2005 criteria (90% vs 73%, p 0.023), and lower diastolic blood pressure (60.81 vs 66.88, p 0.014). There was no difference in pre-OLT CCM per 2019 criteria (19 vs 17%, p 0.758) or MELD-Na score (21.24 vs 19.40, p 0.166). In multi-variable cox regression analysis adjusted for diastolic blood pressure, HRS, ascites, and OLT timing during admission, CCM per 2005 criteria remained significant as seen in Figure 1 (Hazard Ratio = 3, p 0.038).

Conclusion:
CCM per 2005 criteria is an independent predictor of MACE at 13 months post-OLT while CCM per 2019 criteria is not.
Abstract 12827: The Prognostic Value of Peak Mitral Annulus Systolic Velocity in Relation to Incident Heart Failure in the General Population - The Copenhagen City Heart Study
Authors: Davidovski Filip S , Lassen Mats H , Skaarup Kristoffer G , Johansen Niklas D , Jensen Gorm Boje , Schnohr Peter , Mogelvang Rasmus , Biering-Srensen Tor
Published: June 2023

Introduction:
Peak mitral annulus systolic velocity (s’) measured by color tissue Doppler echocardiography can be used to evaluate longitudinal systolic function of the left ventricle (LV). The prognostic value of s’ has previously been documented in patients with ischemic heart disease and heart failure (HF). We sought to investigate the prognostic value of s’ in association with incident HF in the general population with low cardiovascular risk.

Methods:
This prospective cohort consists of participants from the 5th Copenhagen City Heart Study. All participants had echocardiography performed. Exclusion criteria were prevalent HF, prevalent atrial fibrillation and inadequate image quality for s’ assessment. Multivariable Cox regression models adjusted for; sex, age, smoking-status, diabetes, ischemic heart disease, hypertension, heart rate, left atrial volume index and E/e’, were used to assess the association between s’ and HF.

Results:
Of 4,110 participants included (mean age 56 years ± 17.4 year, 56.8% female), 90 (2.2%) developed HF during a median follow-up of 5.4 years, [IQR: 4.4-6.3]. The mean s’ was 6.05 cm/s ± 1.2. Following multivariable adjustment, decreasing s’ remained significantly associated with HF (HR 1.60 (95% CI: 1.24; 2.07 p<0.001) per 1 cm/s decrease) (Figure). An optimal cut-off value for s’ was calculated to be 5.9 cm/s. Participants with s’ below this cut-off had a 3-fold increased risk of HF (HR 3.15 (95% CI: 1.97; 5.03 p<0.001). In participants with s’ ≥ 5.9 cm/s, the incidence rate of HF was 2.1 per 1000 person-years (95% CI: 1.39; 3.09) and 6.5 per 1000 person-years (95% CI: 5.13; 8.31) when s’ < 5.9 cm/s. The cut-off value had a sensitivity of 73.3% (95% CI: 63; 82.1), a specificity of 54.0 (95% CI: 52.4; 55.6), and a negative predictive value of 98.9% (95% CI: 98.4; 99.3).

Conclusion:
In the general population, s’ is an independent prognosticator for the development of HF.

Figure.
The assocation between s’ and HF.
Abstract 12837: A Novel Index to Predict Post-Operative Left Atrioventricular Valve Morbidity in Atrioventricular Septal Defects
Authors: Tsen Yu-Shan D , Burkett Dale , Pan Zhaoxing , Schafer Michal , Jone Pei-Ni
Published: June 2023

Introduction:
Morbidity of the left atrioventricular valve (LAVV) remains the leading indication for reoperation on atrioventricular septal defects (AVSDs). While qualitative 2D and quantitative 3D risk factors have been identified, no quantitative 2D measurement yet exists to predict poor postoperative outcomes. The aim of this study was to evaluate objective measurements of the LAVV and subvalvar apparatus in relation to postoperative outcomes.

Methods:
A retrospective review was performed on 2D echocardiograms of patients undergoing surgical repair of an AVSD from January 1, 2014 to December 31, 2021. Demographic and perioperative data were collected from the electronic medical record. The hingepoint-to-hingepoint length of the superior, mural and inferior bridging leaflets in early diastole, as well as LAVV chordal length at end-diastole were measured and indexed to body surface area. A poor outcome was defined by significant LAVV regurgitation (moderate or greater), LAVV stenosis (5mmHg or greater), need for second cardiopulmonary bypass run, postoperative ECMO, reoperation, or death. LAVV measurements were compared to composite outcome by Wilcoxon rank sum test.

Results:
Of 120 patients with adequate perioperative imaging, 47 (39.2%) had a poor outcome. Indexed LAVV chordal length was significantly different between those who experienced a poor outcome and those who did not, with shorter chordal length predictive of a poor outcome. Interestingly, mural leaflet size was not associated with a poor outcome.

Conclusions:
Indexed LAVV chordal length is a novel measurement shown to predict a poor postoperative outcome in AVSD. Additional analysis is necessary to assess whether short chords are more predictive of LAVV regurgitation or stenosis, and to determine a numeric cut-off of indexed chordal length for predicting poor outcome.
Abstract 12874: A Novel Mechanism in the Pathogenesis of Heart Failure With Preserved Ejection Fraction Through Hexokinase Mitochondrial Dislocation and Substrate Shuttling Into the O-Glcnacylation Machinery
Authors: Tatekoshi Yuki , Shapiro Jason S , Liu Mingyang , Bianco George M , Sharifzad Farzaneh , De Jesus Adam , Koleini Navid , Wasserstrom Andrew , Ardehali Hossein
Published: June 2023

Introduction:
Endothelial cell (EC) dysfunction underlies the pathogenesis of heart failure with preserved ejection fraction (HFpEF), however, the mechanism is unclear. ECs are highly dependent on glycolysis; however, it is not known how their metabolic profile is altered in the setting of HFpEF. Hexokinase 1 (HK1) carries the first step in glycolysis and is mostly bound to the mitochondria in ECs.

Objective:
We sought to elucidate the role of EC glucose metabolism, and specifically HK1, in the development of HFpEF.

Results:
We first showed that among glycolytic enzymes, HK1 is highly specific to ECs, suggesting the significance of HK1 in EC physiology. Although HK1 mRNA and protein levels are not changed, we noted increased dislocation of HK1 from the mitochondria in ECs from HFpEF mice. To study the role of HK1 dislocation in the development of HFpEF, we generated mice with mitochondrial-binding domain of the endogenous HK1 replaced with Flag tag (ΔE1HK1). ΔE1HK1mice develop impaired cardiac relaxation at 20 weeks of age and HFpEF by 40 weeks, and ECs from these mice displayed impaired angiogenic potential. Since HK1 is involved in glucose metabolism, we then performed metabolomic studies and demonstrated that intermediates in hexosamine biosynthetic pathway (HBP) are significantly decreased in ECs from ΔE1HK1 mice. To assess the mechanism for the decrease in HBP, we assessed protein modification, and noted reduced protein N-glycosylation and increased O-GlcNAcylation in ECs from ΔE1HK1. We also demonstrated that inhibition of the key enzyme in O-GlcNAcylation (OGT) reverses the EC dysfunction noted in ΔE1HK1 mice, indicating that O-GlcNAcylation is responsible for the angiogenic defect in ECs from ΔE1HK1. Finally, to provide a mechanism for altered protein glycosylation with HK1 mitochondrial dislocation, we showed that HK1 associates with N-glycosylation machinery when it is attached to mitochondria, while it binds to OGT when it is dislocated from mitochondria.

Conclusion:
Our studies demonstrate a role for HK1 mitochondrial binding and protein O-GlcNAcylation in the pathogenesis of HFpEF, and that HK1 cellular localization plays a major role in the fate of HBP intermediates into either N-glycosylation or O-GlcNAcylation machinery in ECs.
Abstract 12884: Reduction of Alpha-1,4-Galactosyltransferase (A4GALT) by Antisense Oligonucleotide Mitigates Globotriaosylsphingosine (lyso-gb3) Accumulation in Fabry Mice
Authors: Yeap Xin Yi , Wahlander Asa , Yeh Ting-yuan T , Mullick Adam E
Published: June 2023

Fabry disease is one of the most common lysosomal storage disorders that results from a deficiency of the enzyme alpha galactosidase A (GLA). The deficiency leads to systemic accumulation of globotriaosylceramide (Gb3) and its deacylated derivative, Lyso-Gb3, in multiple organs, which can progress into end stage renal disease, heart failure or stroke in Fabry patients. Despite current FDA-approved enzyme replacement and chaperone therapies, unmet medical needs remain. A4GALT is the key enzyme that catalyzes the incorporation of galactose to lactosylceramide to form Gb3. We tested the hypothesis whether a substrate reduction approach utilizing an antisense oligonucleotide (ASO) targeting A4GALT can ameliorate Lyso-Gb3 accumulation in a mouse model of Fabry disease, the α-Gal A knockout (GLA KO). Potent and well tolerated mouse A4GALT ASO leads were identified in wildtype (WT) mice and evaluated in a dose response (5, 20, 40, 80 mg/kg/week) in GLA KO mice. A4GALT reductions of up to 90% were observed in the kidney. Lyso-Gb3 level was determined by LC-MS and was found to be reduced in a dose-dependent manner by up to 75% and 65% in plasma and kidney, respectively. In conclusion, A4GALT ASO treatment in GLA KO mice results in dose-dependent reductions of plasma and kidney lyso-Gb3, a key endpoints of disease efficacy that are monitored in the clinic. Hence, a substrate reduction therapy by inhibiting A4GALT with ASO could be a promising approach for treatment of Fabry disease.