bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16083: How Will the Use of New Heart Failure Treatments Impact US Health System Reimbursement Under Alternative Payment Models: Measuring the Impact of Sotagliflozin Use Among Patients Hospitalized for Heart Failure
Authors: Wang Shanshan , Shafrin Jason , Kim Jaehong , Sikirica Slaven , Sandhu Alexander T
Published: November 2023

Background:
In the SOLOIST-WHF clinical trial, sotagliflozin lowered rates of readmission and emergency department (ED) visits among patients hospitalized for worsening heart failure (HF), but its impact on health systems’ finances is unclear.

Research Question:
What is the economic impact of the adoption of sotagliflozin on health systems after incorporating reimbursement bonuses within alternative payment models (APM)?
Goal:
To quantify the financial impact on health systems of adopting sotagliflozin relative to standard of care (SoC) for treating patients with HF as in SOLOIST-WHF.

Methods:
This study created a decision tree model and estimated the clinical impact of sotagliflozin use relative to SoC from the SOLOIST-WHF trial. The model first assessed the impact of sotagliflozin on re-hospitalization, ED visit rates and mortality. Next, these clinical outcomes were translated into impacts on a health system’s finances relative to SoC within a one-year time frame under traditional fee-for-services (FFS) and three APMs: hospital readmissions reduction program (HRRP), Bundled Payments for Care Improvement (BPCI), and Accountable Care Organization (ACO).

Results:
An average community hospital (6,109 admissions annually) would have 83 patients per year with an index HF hospitalization. Sotagliflozin reduced the probability of re-hospitalization, ED visits, and deaths by 29.3%, 38.5%, and 17.8%, respectively vs. SoC. For hospitals not experiencing capacity constraint, sotagliflozin adoption increased financial returns by $9,365 per person (pp) ($781,340 per health system) under HRRP, $1,200 pp. ($100,106 per health system) for BPCI, and $1,078 pp. ($89,910 per health system) for ACO. (Figure 1)

Conclusion:
Sotagliflozin adoption decreased hospitalizations, ED visits, and deaths, which—under various APMs—led to a net positive financial impact on health systems after accounting for APM bonus payments.

Sponsorship: Lexicon Pharmaceuticals, Inc.
Abstract 16086: Impact of Amyloidosis on the Outcomes of Percutaneous Coronary Intervention Recipients: A Nationwide Analysis
Authors: Raval Maharshi , Singh Sukhnoor , Alencar Arthur , Pethani Yashvi , kommuru Sravani , Sulthana Beegam , Chaudhary Abhishek , Prakash Babu Janani , Elttayef Iman Jasim Elttayef , Siddiq Sajid
Published: November 2023

Background:
Interest in amyloidosis is increasing, primarily due to its high prevalence and recent advances in diagnostic and treatment modalities. The role of amyloidosis in aortic stenosis is established, and in coronary artery disease (CAD) outcomes are being reported. We aim to study the impact of amyloidosis on the outcomes of inpatient percutaneous coronary intervention (PCI) recipients.

Methods:
We conducted a cross-sectional cohort study using the nationwide inpatient sample (NIS) 2018-19. We included 457,730 adult inpatients with CAD managed with PCI and further divided by the presence of a co-diagnosis of amyloidosis. A logistic regression model was used to evaluate the odds ratio (OR) of the association between amyloidosis and various outcomes in PCI recipients.Results: Out of the total of 457,730 patients included, 30,905 (6.75%) had amyloidosis. Mean age (66.3 vs. 65.9), female sex (35.6% vs. 32.1%), and African American race (11.6% vs. 9.4%) were higher in the amyloidosis cohort (all P<0.001). The amyloidosis cohort also had a higher incidence of acute kidney injury (AKI) (29.9% vs. 15.5%), complications of surgical care (1.7% vs. 0.7%), complications of cardiovascular implant (9.5% vs. 8.5%), major loss of function (54.7% vs. 27.8%), length of stay (LOS) in days (6.3 vs. 3.8), total charges in $ (166,001 vs. 121,718), and in-hospital mortality (4.7% vs. 2.6%) compared to non-amyloidosis cohort (all P<0.001). Amyloidosis was associated with higher odds of in-hospital mortality (OR 1.3, 95CI 1.23-1.39, p<0.001), AKI (OR 1.89, 95CI 1.83-1.94, p<0.001), and complications of surgical care (OR 2.05, 95CI 1.87-2.26, p<0.001) but not with complications of cardiovascular implant (OR 1.01, 95CI 0.97-1.05, p=0.703).

Conclusions:
Amyloidosis is associated with worse outcomes in inpatient recipients of PCI. Further studies are needed to assess the implications, safety, and outcomes of elective PCI in patients with amyloidosis.
Abstract 16094: Depressive Disorder and Quality of Life in Patients With Heart Failure
Authors: Cañavera Massiel K , Hernandez Camilo A , Carvajal Juan F , Ochoa Miguel E , Luna-Gonzalez Maria L , Diaz Mayra A
Published: November 2023

Background
According to the WHO 17.9 million people die every year owing to cardiovascular disease. Due to the increase in prevalence, heart failure (HF) is an important public health problem with more than 23 million people; its prevalence is expected to increase 46% by 2030. The presence of depression can affect up to 21.5% patients with HF, deteriorating quality of life with an increase in hospitalization and mortality rates.

Aims
Evaluate the factors associated with depressive symptoms and quality of life in patients with HF.

Methods:
Observational, analytical, transversal study with secondary analysis of 153 patients with HF treated in an outpatient clinic, considering baseline characteristics, echocardiogram parameters and depressive/quality of life PHQ-9 and Minnesota scales for univariate and bivariate analysis.

Results:
There was an association between the compromise of NYHA III-IV vs NYHA I-II functional class with: moderate to severe degree of depression (44,44% vs 24,9%) and impaired quality of life (61.11% vs 26.54%) p≤ 0.001, respectively. Likewise, statin use was associated with less depression (30.23% vs 11.82% p=0.006) and quality of life improvement (32,56% vs 14,55% p=0.012) respectively, this was independent of psychosocial support. Atrial fibrillation had a significant association with depression (p=0.030) and history of cerebrovascular disease (p=0.009).

Conclusion:
Depression is an important and common comorbidity that often coexist in patients with HF and are associated with poor quality of life. It is important to screen for depressive symptoms in these patients with the goal to provide appropriate treatment and avoid negative outcomes.
Abstract 16097: Association of Neighborhood Income and Outcomes in Atrial Fibrillation: A Nationwide Retrospective Cohort Analysis
Authors: Kotta Prasanti Alekhya , NAMBI VIJAY , Misra Arunima , Chelu Mihail G , Nasir Khurram , Abramov Dmitry , Minhas Abdul Mannan Khan
Published: November 2023

Introduction:
The impact of socioeconomic status on atrial fibrillation (AF) outcomes is not well understood. We studied the association between household income and clinical outcomes in AF hospitalizations.

Methods:
We conducted a retrospective analysis of adult primary AF hospitalizations from the United States National Inpatient Sample (NIS) between 2016 and 2020. Quartile classification of the median household income of the zip code of the patient’s residence provided by NIS was used. Among the four income quartiles, lowest quartile was used as reference category. Weighted multivariable logistic and linear regression, adjusting for multiple patient and hospital-level characteristics (Table 1), were performed. We aimed to study patient characteristics and clinical outcomes in AF based on household income.

Results:
From lowest to highest income quartile, mean age and proportion of White race increased; proportion of females, Black, and Hispanic race decreased (Table 1). Compared with lowest income residents, highest income residents had lower in-hospital mortality (Odds ratio [OR] 0.78, 95% confidence interval [CI] 0.7, 0.87, P < 0.001), lower disposition to care facility (OR 0.86, 95% CI 0.83-0.9, p < 0.001), lower length of stay (adjusted mean difference -0.26, 95% CI -0.30, -0.22, P < 0.001), higher procedure utilization including catheter and surgical ablation, atrial appendage closure, electrical cardioversion, and higher healthcare costs ($12,124 vs 10,018)(Table 1).

Conclusions:
We identified significantly higher adverse events and lower procedural/resource utilization in the lower-income residents compared to higher-income residents. Further research is needed to better understand these disparities, their impact on clinical outcomes, and strategies to improve healthcare disparities between SE groups.
Abstract 16098: Cardiovascular Outcomes in Patients Hospitalized With Chronic Kidney Disease and COVID-19: A Nationwide Propensity-Matched Analysis
Authors: Challa Abhiram , Wanjala Stephen , Vasudeva Rhythm , Polana Tejasri , MUNGUTI CYRUS , Vindhyal Mohinder Reddy
Published: November 2023

Introduction:
There is limited data describing the cardiovascular outcomes in patients with coronavirus 2019 (COVID-19) and chronic kidney disease (CKD). This study aims to investigate the impact of CKD on cardiovascular outcomes in patients hospitalized with COVID-19.

Goals:
To assess mortality, readmission, and other in-hospital cardiovascular outcomes in COVID-19 patients with and without CKD.

Methods:
Patients >18 years hospitalized with a diagnosis of COVID-19 were identified in the 2020 National Readmissions Database. Patients with CKD 3, 4 and 5 were subsequently identified using relevant ICD-10 codes. Nearest propensity score matching was conducted using a 1:1 ratio for several demographic, social, and clinical variables. Outcomes with <10 cases were excluded per HCUP rules.

Results:
Amongst 5,831 COVID-19 patients identified, 599 had either CKD stage 3, 4 or 5. Baseline characteristics are shown in Table 1. After matching, CKD was associated with higher rates of acute heart failure (HF) and acute kidney injury (AKI). Our analysis did not find any significant differences in mortality or readmission rates.

Conclusions:
Our analysis found a higher rate of Acute HF and AKI among COVID-19 patients with CKD 3-5 compared to those without CKD. Additional studies are needed to further characterize this observation.
Abstract 16909: Eicosapentaenoic Acid and Docosahexaenoic Acid Have Competing Effects on Membrane Lipid Dynamics Due to Differences in Structure
Authors: Sherratt Samuel C , Shrivastava Sandeep , Libby Peter , Bhatt Deepak L , Chattopadhyay Amitabha , Mason Preston
Published: November 2023

Background:
Omega-3 fatty acids (n3-FAs) incorporate into vascular cell membranes where they modulate protein function and signal transduction. The n3-FA eicosapentaenoic acid (EPA) delivered in ethyl ester form (icosapent ethyl) reduced a broad range of cardiovascular events in high-risk patients (REDUCE-IT). This was not observed with mixed n3-FA formulations containing docosahexaenoic acid (DHA) in STRENGTH and other trials. These discordant outcomes indicate DHA may counter certain EPA effects due to its additional carbons and double bond. We compared these n3-FA effects on membrane lipid dynamics and width, key determinants of protein function.

Methods:
Membrane lipid fluidity was measured by fluorescence anisotropy approaches in large unilamellar vesicles (LUVs) of 100 nm diameter containing 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC) and 50 mol% cholesterol with EPA and/or DHA (0-10 mol%). LUVs were treated with the fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene (DPH), at 1 mol% and evaluated using a spectrofluorometer with a polarization accessory. Membrane width (
i.e
., unit cell periodicity) of the samples was determined by small angle x-ray scattering (SAXS).

Results:
DHA alone increased bulk lipid fluidity as indicated by a dose-dependent reduction in apparent rotational correlation time (ARCT); at 10 mol%, there was a ~20% (p<0.05) reduction from ~19 to ~16 nsec compared to control (untreated membranes). By contrast, EPA had no significant disordering effect except when combined at equimolar levels; the EPA/DHA combination showed a reduction in ARCT to ~18 nsec at 10 mol% that was different from EPA alone (p<0.05). Consistent with these findings, SAXS analysis showed DHA containing membranes had a reduced width compared to EPA by 5% or 3 Å (p<0.05) due to increased
trans-gauche
isomerizations in the phospholipid acyl chains.

Conclusion:
EPA maintained membrane fluidity while DHA increased fluidity and thereby reduced membrane width due to its additional carbons and double bond. The EPA/DHA combination increased membrane fluidity compared to control and EPA alone. The disordering effects of DHA may counter EPA stabilizing effects and explain discordant clinical outcomes with different n3-FA formulations.
Abstract 16924: Lateral T Wave Inversion in Adolescent Individuals: The Beat-It Cardiac Screening Program
Authors: Abela Mark , Tiziana Felice , Sammut Mark , Scerri Christian , Grech Victor
Published: November 2023

Introduction:
Cardiac screening is mandated by most sporting organisations. A resting 12-lead ECG may identify individuals who harbour cardiac disorders who may be at risk of sudden cardiac death (SCD). Lateral wave inversion (TWI) may identify subjects with cardiac phenotypes that are linked to SCD.

Aim:
The aim of this study was to ascertain the prevalence of lateral TWI in adolescent individuals as part of a systematic nationwide cardiac screening. The yield of family screening in these probands was also evaluated.

Methodology:
A national cardiac screening program (BEAT-IT) was set up in the 2017/2018 scholastic year for students attending year 11 classes. 2672 students (14-17 years) and their legal guardians gave consent. Screening protocol consisted of a questionnaire/ECG at school. ECGs were reported as per the ‘International Recommendations for ECG interpretation’ (2017). Those with contiguous TWI in ≥2 lateral leads were evaluated. An athlete was defined as an individual who participated in organized sport and/or engaged in >4 hours of physical activity weekly.

Results:
2672 adolescents gave consent (mean age 15 years, 50.4% female, 95.8% Caucasian, 39.0% athletes). 6 (0.22%) had lateral TWI, extending into the inferior (n=4, 0.15%) or anterior (n=2 (0.07%) leads. The prevalence was the same in both genders (p=0.477) and athletic status (p=0.580). 2 (0.07%) had symptoms, 4 (0.15%) were female, all were Caucasian, 3 (0.11%) were athletes. 4 (0.15%) had borderline or other pathological ECG changes (n=2 LAE, n=1 RAE, n=1 ST depression). 4 (0.15%) had deep TWI (≥2mm). One patient was diagnosed with HCM (0.04%). All subjects are under surveillance. Family screening in relatives (n=27) identified two (7.4%) with cardiomyopathy (n=1 HCM, n=1 DCM). Another 5 (18.5%) had an abnormal ECG requiring surveillance. These findings suggest that some of the participants identified at screening may harbour pre-clinical phenotypes.

Conclusion:
Lateral TWI is an infrequent finding in young individuals and requires surveillance as it may be a manifestation of heart disease. Family screening may help increase the degree of suspicion of pre-clinical disease in peripubertal individuals.
Abstract 16929: Defining Thresholds for Meaningful 30-day Health Status Changes Following Transfemoral Carotid Artery Stenting
Authors: Kluger Jonathan , Romain Gaelle , Cleman Jacob , Scierka Lindsey , Grubman Scott , Pajarillo Carmen S , Schenck Christopher , Mena-Hurtado Carlos , Smolderen Kim G
Published: November 2023

Introduction:
Carotid artery stenosis treatment trials have focused on clinical endpoints such as stroke, death, and MI, but evidence of carotid revascularization’s impact on health status is limited. This study aims to establish minimal clinically important differences (MCIDs) to assess clinical improvement or worsening from the perspectives of patients with carotid artery stenosis undergoing transfemoral carotid artery stenting (TF-CAS).

Methods:
We studied patients in the multicenter Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) registry who underwent TF-CAS between 2010 and 2014 and who completed either the EQ-5D-3L or SF-36, two generic health-related quality-of-life surveys. Distribution-based MCIDs were calculated as 0.5 standard deviations for 30-day changes in health status scores post-TF-CAS for the EQ-5D-3L index value and visual analog scale (VAS) subscales and the SF-36 mental and physical component summary (MCS and PCS) subscales. We then stratified this analysis by symptom status (presence or abscence of prior stroke or TIA).

Results:
The study included 3,930 patients (27.7% symptomatic) who completed the EQ-5D-3L and 3,018 (30.5% symptomatic) who completed the SF-36. The MCIDs for the overall cohorts were 0.09, 11.02, 4.73, and 5.39 for the EQ-5D-3L index value, EQ-5D-3L VAS, SF-36 MCS, and SF-36 PCS, respectively. All MCIDs are summarized in Table 1. The MCIDs for each subscale were similar between asymptomatic and symptomatic subpopulations.

Conclusions:
Distribution-based thresholds for improvement and worsening of health status in patients undergoing TF-CAS were established for commonly-used generic health status instruments. These reference values can be used in both symptomatic and asymptomatic disease and will be important for interpreting future trial results focusing on the benefit of TF-CAS from patients’ perspectives.
Abstract 16930: Patient Perceptions of Multilevel Nudges About Cardiovascular Medication Refills: A Qualitative Analysis
Authors: Gupta Prerna , McLeod Kaitlyn , Caputo Sandy Lisa , Waughtal Joy , Khazanie Prateeti , Allen Larry A , Peterson Pamela , Bull Sheana , Ho Michael
Published: November 2023

Introduction:
Nudges are simple messages designed to elicit behavior change. In a multi-center pragmatic clinical trial, we embedded nudge messages into short message service texts (SMS) to encourage patients to refill medications to improve medication adherence. In this study, we assessed patient perceptions of the nudge messages.

Methods:
We conducted in-depth, open-ended interviews with a sample of English and Spanish speaking patients with cardiovascular disease and documented medication refill gaps enrolled in the clinical trial from a tertiary care academic center, UCHealth, and an urban safety-net hospital, Denver Health. We transcribed interviews and performed content analysis to identify themes. Patients were interviewed about their experiences over the phone using interview guides and perceptions of the nudge messages. Content analysis was done by a trained reviewer to identify themes.

Results:
Among 12 interviews (4 in Spanish), all appreciated the nudge messages, even though some had successful systems to remind them of medications already. All patients interviewed had no concerns about the messages because they were discreet and respected patient privacy. Some patients felt the health system was caring for them by sending messages. Suggestions for improvement included: 1) medications instructions, such as whether to take them with food; 2) dietary education; and 3) reminders for taking medication in the middle of the day, the doses that were more likely to be missed. Despite liking the messages, most self-reported no change in their medication taking behavior due to reminders they had set up themselves. They did, however, appreciate the nudge messages, and a few patients stated that the messages helped them ‘stay on track’ with refills.

Conclusions:
Patients appreciated the nudge messages that encouraged them to pick up medication, and generally felt supported by the healthcare system in receiving them. Most patients had no suggestions for improving the nudges. Self-reported behavior change in taking medications was low, though patients’ statements suggested the messages were still helpful with refills. True behavior change will be revealed in the final quantitative analysis of the trial.
Abstract 16938: Epicardial Adipose Tissue on the Risk of Lethal Ventricular Arrhythmias in Patients With Nonischemic Cardiomyopathy Receiving Implantable Cardioverter-Defibrillator
Authors: Nakamori Shiro , Yazdanian Forough , Rodriguez Jennifer , Yue Jennifer , Street Jordan , Kramer Daniel B , Ngo Long H , Manning Warren J , Nezafat Reza
Published: November 2023

Background:
The arrhythmic risk stratification in patients with nonischemic cardiomyopathy (NICM) remains challenging. The implication of epicardial adipose tissue (EAT) on incident sudden cardiac death (SCD) is unclear.
Objectives:
To assess the relationship between EAT and SCD in NICM patients receiving implantable cardioverter-defibrillators (ICD) and compare this risk to patients with ischemic cardiomyopathy (ICM).

Methods:
A total of 421 patients scheduled for primary or secondary prevention ICD implantation underwent CMR at 1.5 or 3T, including cine and late gadolinium enhancement (LGE) imaging. EAT volume surrounding both ventricles was quantified with manual delineation on cine short-axis images and calculated by summation of EAT volume of each slice using the modified Simpson rule. LGE was semiautomatically quantified by adjusting a grayscale threshold. The primary endpoint was a composite of ICD therapy, including anti-tachycardia pacing and SCD.

Results:
We identified 265 NICM patients (mean age 54 years, 73% men), with LGE present in 152 patients (57%), including 85 patients (32%) with secondary prevention ICD. During the median follow-up of 2.9 years, 42 patients (16%) experienced the endpoint. Low EAT was associated with an increased risk of SCD in NICM patients (HR
ad
per 10ml decrease, 1.54; 95%CI, 1.19-1.96, p<0.001), even after adjustment for other relevant disease variables. A continuous relationship was evident between EAT and subsequent ICD therapies (p=0.001). Even when considering 85 patients with secondary prevention ICD as theoretically having an SCD event, the risk of EAT in predicting SCD remained essentially unchanged. In contrast, EAT was not associated with increased SCD risk in ICM patients.

Conclusions:
Low EAT was associated with increased SCD risk in NICM patients receiving ICD implantation, especially primary prevention ICD. These data suggest a potential role of EAT in identifying NICM patients at risk of SCD.
Abstract 16940: Nutrient Intake of Patients With Heart Failure: Different Profiles Reveal Different Intervention Targets
Authors: Thompson Jessica H , Biddle Martha J , Lee Christopher S , Lennie Terry A , Kang JungHee , Moser Debra K
Published: November 2023

Introduction:
Diet quality is an important, but often underappreciated part of heart failure (HF) care. Tailoring of dietary interventions must take into consideration how patients with HF eat.

Purpose:
To identify distinct dietary profiles representing eating patterns in patients with HF.

Methods:
This was a secondary analysis of data from a randomized controlled double-blind clinical trial of a nutrition intervention with patients with HF. Baseline dietary data were collected using 24-hour dietary recall that included a weekend and two weekdays. Nutritional data were generated from the Nutrition Data Systems for Research. Nine unique diet components were quantified (along with a total Healthy Eating Index) and included in modeling based on theoretical and empirical knowledge: sodium, added sugars, trans-fat, vitamin C, vitamin D, vitamin E, folate, beta-cryptoxanthin, and lutein + zeaxanthin. Latent class mixture modeling was used to identify distinct dietary profiles among these 9 components representing different eating patterns that could serve as the bases of future interventions.

Results:
There were 112 participants with an average age 63 ± 12, 59.8% male, and 62.5% with class III or IV HF. Two dietary profiles were identified and were labeled by the prominent dimensional characteristic. The “higher intake” profile (n=79 (69.9% of the sample)) had significantly higher intake levels of sodium, vitamin D, vitamin E, vitamin C, beta-cryptoxanthin, lutein + zeaxanthin, and folate, and a “lower intake” profile (n=34 (30.1% of the sample) had significantly lower intake of these same nutrients. Patients with HF in the lower intake profile also had significant higher quality diets (Healthy Eating Index = 63.7± 13.2) compared with those in the higher intake profile (Healthy Eating Index = 53.9 ± 14.2, p<0.001).

Conclusion:
Two different nutrient patterns were identified that would be amenable to different interventions; one focused on total calorie reduction and the other focused on optimizing nutrient intake.
Abstract 16946: The Optimal Surgical Procedure of Mitral Valve Repair According to Risk Analysis of Postoperative Functional Mitral Stenosis
Authors: Matsuda Masaru , Domae Keitaro , Yokota Junki , Kodani Noriko , Sakamoto Tomohiko , Kuratani Toru , Hata Masatoshi , Masai Takafumi , Sawa Yoshiki
Published: November 2023

Background:
Functional mitral stenosis (FMS) after mitral valve repair (MVr) is associated with pulmonary hypertension in the late period, increasing the risk of re-operation and deterioration of long-term outcomes. However, the risk factors for FMS after MVr, especially the impact of surgical procedures, have not been thoroughly investigated.

Hypothesis:
We hypothesize that procedures of valve repair, including prosthetic ring orifice area (ROA), may be associated with FMS in the late period.

Methods:
We retrospectively evaluated 205 patients who underwent MVr using full annuloplasty rings between 2011 and 2021 at our institution. FMS was defined as mean trans-mitral pressure gradient (TMPG) ≥8 mmHg measured by annual echocardiography. ROA was determined by calculating the internal area of each valve type and size. Perioperative factors such as repair techniques, ROA, and ROA divided by BSA (ROAi) were used to analyze risk factors for FMS. The mean follow-up period was 4.8±0.4 years.

Results:
MVr was performed using artificial chordae in 110 cases and intervention in valve leaflet in 83 cases (resection suture: 43, cleft closure: 26, plication: 12, and edge-to-edge repair: 8). We also utilized semi-rigid full ring in all cases (26 or less: 15, 28: 53, 30: 73, 32: 49, 34 or more: 15). We identified postoperative FMS in 23 cases (11.2%, 2.5±0.9 years after MVr) with TMPG of 9.0 ± 0.7 mmHg. In the FMS group, decreasing TR-PG in the late period was not achieved after MVr. TR-PG in the late period was also significantly higher in the FMS group (28.3 ± 5.8 vs. 20.3 ± 2.1 mmHg, p=0.01). The freedom from re-operation for MV and re-hospitalization for heart failure rate was not significantly different in the two groups (93.6% vs. 95.5%, p=0.32, 87.7% vs. 90.6%, p=0.36, respectively). However, the freedom from MACE rate was lower in the FMS group (81.4% vs. 86.3%, p=0.11). Univariate analysis demonstrated that intervention in valve leaflet (OR 2.53, p=0.04) and ROAi (OR 0.98, p=0.005) were significant risk factors for FMS.

Conclusion:
Although further follow-up is mandatory, these results suggested that the use of sufficiently large prosthetic ring and avoidance of intervention in valve leaflet are efficient for preventing FMS and improving clinical outcomes after MVr.
Abstract 19126: Discovery of TMEM65 as a Positive Regulator of Mitochondrial Calcium Efflux
Authors: Garbincius Joanne F , Salik Oniel , Mangold Adam S , Makhoul Angelina D , Schmidt Anna E , Khalil Dima Y , Doolittle Josh J , Murray Emma K , Lazaropoulos Michael P , Tomar Dhanendra , Elrod John W
Published: November 2023

Introduction:
The balance between mitochondrial calcium (
m
Ca
2+
) uptake and efflux regulates ATP production, but if perturbed causes
m
Ca
2+
depletion and energy starvation or
m
Ca
2+
overload and cell death. Disrupted
m
Ca
2+
homeostasis is implicated in ischemia-reperfusion injury, heart failure, and neurodegeneration. The mitochondrial sodium-calcium exchanger, NCLX, is a critical route of
m
Ca
2+
efflux in excitable tissues, supporting NCLX as a promising therapeutic target to limit pathogenic
m
Ca
2+
overload in organs like the heart and brain. However, a critical barrier to translation is that little is known about the mechanisms controlling NCLX activity.

Goals:
We used proximity biotinylation screening to identify the NCLX interactome and proteins that may regulate NCLX function. We identified TMEM65, a mitochondrial inner membrane protein of unknown function, as an NCLX-proximal protein.

Hypothesis:
Null mutation of
TMEM65
causes mitochondrial encephalomyopathy and phenocopies genetic NCLX disruption. Therefore, we hypothesized that TMEM65 modulates
m
Ca
2+
efflux through NCLX.
Approach:
Here, we used measurements of
m
Ca
2+
exchange in AC16 cardiomyocytes with TMEM65 overexpression (OE) or CRISPR/Cas9 genetic disruption of
TMEM65
to test TMEM65’s effect on
m
Ca
2+
flux and its functional dependence on NCLX. We used AAV-mediated
Tmem65
knockdown (KD) and TMEM65 OE in mice to assess the effects of gain- or loss of TMEM65 expression on cardiac function.

Results:
TMEM65 OE potently enhanced
m
Ca
2+
efflux
in vitro
, and NCLX inhibition with CGP-37157 mitigated this effect. Knockout of
TMEM65
attenuated
m
Ca
2+
efflux.
In vivo
Tmem65
KD reduced left ventricular fractional shortening and reduced S293 phosphorylation of pyruvate dehydrogenase in the heart, indicative of increased
m
Ca
2+
loading.
In vivo
TMEM65 OE did not alter cardiac function.

Conclusions:
We conclude that TMEM65 has an essential function to promote
m
Ca
2+
efflux, likely via positive regulation of NCLX, and is critical to limiting deleterious
m
Ca
2+
overload in the intact heart. Ongoing work is defining the functional interactions between TMEM65 and NCLX, and establishing the utility of targeting TMEM65 to restore
m
Ca
2+
homeostasis in heart failure and other excitable tissue diseases.
Abstract 19132: Covid-19 Incidence, Mortality, and Disparities for Cancer, Cardio-Oncology, and The General Population: Machine Learning National Analysis of 27 Million Hospitalizations in 2020
Authors: Ynalvez Leslie , Monlezum Dominique , Ali Abdelrahman , Shadid Husam , Seal Zachary , Pushparaji Bala , Koutroumpakis Efstratios , Park Jong Kun K , Cilingiroglu Mehmet , Marmagkiolis Konstantinos , Iliescu Cezar
Published: November 2023

Introduction:
The paucity of large, longitudinal COVID data for higher risk cancer and cardio-oncology patients limits sufficient preparedness for the next pandemic. Therefore, questions regarding the incidence, outcomes, and disparities for the above patients need to be studied.

Methods:
BAyesian Machine learning-augmented Propensity Score translational (BAM-PS) statistics with multivariable regression was performed on the largest all payor US inpatient dataset, the National Inpatient Sample.

Results:
Of the 27,667,386 adult hospitalizations in 2020, 47,820 (0.17%) had COVID, of whom 2,430 (5.08%) had active cancer and 765 (1.60%) had cardio-oncology disease. In 2020, COVID was significantly less likely in patients with versus without active cancer (0.12% versus 0.18%, p<0.001), with the most common malignancies in COVID including leukemia (22.22%), multiple myeloma (14.20%), lung (13.79%), and non-Hodgkin lymphoma (11.93%). The odds of being treated inpatient for COVID was significantly reduced by active cancer (OR 0.66, 95%CI 0.60-0.73, p<0.001). In active cancer, COVID significantly increased mortality (OR 2.02, 95%CI 1.52-2.68, p<0.001), though within COVID, neither active cancer nor cardio-oncology disease significantly increased mortality. In active cancer with COVID, mortality was significantly increased for the East South Central region (OR 0.08, 95%CI 0.01-0.95, p=0.045) compared to the New England region, though there were no other disparities by race, insurance, income, or urban density (with no disparities in cardio-oncology).

Conclusions:
This large nationally representative machine learning analysis suggests that cancer patients with COVID were less likely to be treated inpatient despite increased mortality. Cardiovascular disease does not significantly contribute to the mortality of these already extremely frail and complex patients.
Abstract 19134: Association Between CHA
2
DS
2
-VASc and LA Volume Index: Insights From DECAAF II
Authors: Assaf Ala' Y , Noujaim Charbel , Mekhael Mario , Chouman Nour , Shamaileh Ghaith , Kreidieh Omar , donnellan eoin , Pandey Amitabh C , Feng Han , McGarvey Cecile , Lim Chanho , Marrouche Nassir
Published: November 2023

Introduction:
LA Volume is strongly associated with atrial fibrillation (AF) and underlying atrial myopathy. The CHA
2
DS
2
-VASc score predicts stroke risk in patients with AF. The aim of this study is to investigate the relationship between the two.

Methods:
In this subanalysis of the DECAAF II trial, patients with persistent AF undergoing first-time catheter ablation underwent a baseline late gadolinium enhancement magnetic resonance imaging (LGE-MRI) within one month prior to ablation. LA Volume Index (LAVI) was defined as LA Volume on the MRI prior to ablation divided by body surface area (
mL/m2
). The CHA2
DS2
-VASc score was also calculated at baseline prior to ablation. Analysis of Variance (ANOVA) test and linear regression were used to study the association between the two.

Results:
815 patients were included, (78.9% males, mean age 62.7 ± 9.1 years) (table). The mean LAVI was 62.2 ± 18.9 mL/m2, and mean CHA2
DS2
-VASc score was 1.7 ± 1.27. The ANOVA test showed significant differences between group (F = 7.71, p <0.001). For every point increase in CHA2
DS2
-VASc score, LAVI increases by 3 (LAVI = 2.99 * CHA2
DS2
-VASc + 57; p <0.001) (figure).

Conclusions:
Our data suggests that structural remodeling in patients with AF is likely driven by multiple factors. There was a clear association between CHA2
DS2
-VASc score and higher LAVI. Serial analysis of LA Volume at different time points is needed to further understand the impact of individual comorbidities on LA volume dilation.
Abstract 19136: Barriers to Equitable Access to Acute Stroke Care in Hawaii: Logistical and Socioeconomic Effects on Stroke Care in an Island Chain
Authors: Torigoe Trevor H , Morioka Taysia , Kahili-Heede Melissa , Hui Ferdinand , Koenig Matthew , Nakagawa Kazuma
Published: November 2023

Introduction:
Stroke is the leading cause of chronic disability and third-leading cause of mortality in Hawaii. State incidence of stroke is lower (2.9% to 3.4%) but mortality is higher (70.3:100,000) compared to the rest of the country (58.1:100,000). Access to comprehensive acute stroke care is complicated by geographical restrictions including topography and isolation between islands and also socioeconomic factors such as cost of living. The Queen’s Medical Center (QMC, Honolulu, Oahu, HI) is the sole comprehensive stroke center in the state.

Hypothesis:
Access to comprehensive stroke care and thrombectomies will be negatively correlated with both travel time and increased geographical barriers.

Methods:
Retrospective review of records from QMC between January 2021 to June 2023 identified 405 patients with an acute stroke and underwent thrombectomy. Patient zip codes were used to create a heat map identifying locations of patients receiving thrombectomy. Another heat map was made for all acute stroke cases using public health data. An index was created to determine travel time from zip code to QMC. Thrombectomy and acute stroke versus travel time was performed using generalized linear models.

Results:
GIS-generated heat maps demonstrate a difference in care opportunities between zip codes, identifying areas with highest incidence of acute stroke associate with lower rates of thrombectomy procedures. Island barriers create the highest differences in acute stroke cases versus thrombectomy procedure. Regression analysis demonstrated marked negative correlation in comparison between thrombectomies versus acute stroke cases with respect to travel time.

Conclusions:
Healthcare providers in Hawaii face an increased challenge with respect to providing care due to natural geography that extending the time to comprehensive stroke treatment. Hawaii is acutely aware of the unique challenges and the results of this study are an initial phase in providing a framework for modified statewide acute stroke protocols that can further be utilized by other communities with similar barriers to access to care.
Abstract 19137: Chronic Kidney Disease is an Important Predictor of 2-Year Mortality After Chronic Limb Ischemia Repair Using Either Endovascular or Bypass Graft Intervention
Authors: Wang Angela , Solano Antonio , Miller Richard Tyler , Timaran Carlos H , Modrall J. Gregory , Tsai Shirling , Kirkwood Melissa L , Ramanan Bala
Published: November 2023

Introduction:
Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are associated with worse outcomes after both endovascular (PVI) and bypass graft intervention (OI) of critical limb ischemia (CLI). Research Question: Do surgical outcomes of CLI repair differ by approach and CKD severity?

Methods:
Patients undergoing elective CLI intervention with preoperative renal function data captured by the Vascular Quality Initiative between Jan 2003 and Dec 2018 were analyzed. Patients were stratified by CKD class: normal/mild (CKD stage 1-2), moderate (CKD stage 3a), moderate-severe (CKD stage 3b), severe (CKD stage 4-5), and dialysis. Primary outcomes were 30-day, 1-year, and 2-year mortality, and incidence of major amputation. Predictors of survival were identified by Cox multivariate regression.

Results:
Out of 18,399 patients who underwent elective CLI treatment, 13,366 had PVI and 5033 had OI. Table 1 demonstrates the distribution of patients and primary outcomes. On Kaplan Meier analysis, 2-year survival favored the normal/moderate CKD cohort after both PVI and OI. On Cox regression analysis, when compared to normal/ mild CKD, CKD Class 3b (HR 1.405, p<0.001) and Class 4 (HR 1.712, p<0.001), and Class 5 (HR, 1.649, p = 0.070) were associated with worse 2-year mortality after OI. When compared to normal/mild CKD, CKD Class 3b (HR, 1.427 [1.2-1.7], p<0.001), Class 4 (HR, 2.256 [1.77-2.87], p<0.001), and Class 5 (HR, 1.210 [.59-2.5], p = 0.603) were associated with worse 2-year mortality. 2-year amputation rates did not demonstrate statistically significant differences among CKD classes.

Conclusion:
CKD severity is an important predictor of 2-year mortality after CLI repair regardless of approach but does not predict 2-year major amputation rates. Overall, PVI is associated with lower mortality and major amputation.
Abstract 19150: DUSP1 is Associated With Map-Kinase Signaling in Antigen Presenting Cells Contributing to Salt-Sensitivity of Blood Pressure
Authors: Arshad Suha , Pitzer Mutchler Ashley , Saleem Mohammad , Ertuglu Lale A , Sheng Quanhu , Kirabo Annet
Published: November 2023

Salt sensitivity of blood pressure, a pathological response characterized by a marked increase in blood pressure following salt intake, acts independently of hypertension as a risk factor for cardiovascular morbidities. Our recent research has elucidated a mechanism of sodium entry into antigen presenting cells through epithelial sodium channels (ENaC), which leads to the formation of neoantigen presenting isolevuglandin protein adducts via oxidative stress. Reactive oxygen species present in the cell may impact inflammation response as well as other intracellular pathways, chiefly the MAPK pathway. Previous studies have established an inhibitory connection between the protein-coding phosphatase DUSP1 and MAPKs. We hypothesize that DUSP1 acts as a negative regulator of MAPK signaling pathways involved in the immune response to salt-sensitive hypertension. To test our hypothesis, we isolated human monocytes from healthy participants (N=11) and treated them with either normal (150 mMol/L) or high (190 mMol/L) Na+ for 72 hours in vitro. Analysis of bulk RNA sequence data points to a significant upregulation of DUSP1 in the high salt environments compared to normal salt levels (4339 ± 770.1 vs 2721 ± 546.4 , p=0.0192). We also found that the high salt treatment led to increased expression of ERK1 (HS:2066 ± 184.0 NS:1560 ± 136.7 p= 0.0652), ERK2 (HS:8364 ± 669.8 NS:6256 ± 578.3 p= 0.0281), JNK (HS:1069 + 102.2 NS:792.3 ± 74.85 p= 0.0336), and p38 (HS: 4062 ± 329.0 NS:3010 ± 292.5, p= 0.0336). To study further, we enrolled 9 hypertensive participants who discontinued anti-hypertensive therapy for 2 weeks in an inpatient protocol to phenotype them through rapid salt loading and depletion. Blood pressure was recorded and blood collected at baseline, after salt loading, and after salt depletion and CITE-Seq analysis was performed on isolated PBMCs. After salt loading, we found a negative correlation between both p38 expression and pulse pressure (r= -0.7564 p= 0.0299) and p38 expression and systolic blood pressure (r= -0.8371, p=0.0095). We found a positive correlation between DUSP1 expression and systolic blood pressure after salt depletion (r= 0.7089, p=0.0490). These results suggest that DUSP1 plays an important role in salt sensitivity of blood pressure.
Abstract 19163: A Rare Case of Pericarditis as an Initial Manifestation of Rheumatoid Arthritis
Authors: Majid Muhammad , Arockiam Aro Daniela , Yaker Zachary , Atar Mustafa , Agrawal Ankit , Kumar Ashwin , Klein Allan L
Published: November 2023

Case Presentation:
A 69-year-old male with a history of chronic recurrent pericarditis presented with a 3-week episode of chest pain. Despite treatment with ibuprofen, colchicine, prednisone, and anakinra, he experienced multiple flares upon attempting to wean off anakinra. His current workup revealed an elevated C-reactive protein and an echocardiogram showing a small pericardial effusion. Cardiac magnetic resonance imaging showed mild pericardial late gadolinium enhancement and increased pericardial signal on T2 STIR imaging, confirming a flare of recurrent pericarditis. The patient was started on rilonacept while being weaned off anakinra. During a follow-up after 3 months, the patient reported new onset polyarthralgia, prompting a referral to rheumatology. Rheumatoid factor was negative, but anti-citrullinated protein antibodies were positive, leading to a diagnosis of rheumatoid arthritis (RA). Azathioprine was added to the treatment regimen alongside rilonacept.

Discussion:
The patient's recurrent pericarditis was initially considered idiopathic but, with the subsequent RA diagnosis, it was suspected that RA may have been the underlying cause. While pericarditis is a known cardiac complication of RA, it is uncommon for pericarditis to be the initial manifestation of RA. Anakinra and rilonacept are both interleukin-1 (IL-1) inhibitors, with anakinra being FDA-approved for RA treatment. However, rilonacept has not been extensively studied in patients with RA. The case suggests that the use of certain medications may have masked RA symptoms, and as those medications were tapered, the RA symptoms became more evident. This case highlights the possibility of idiopathic pericarditis evolving into an autoimmune etiology, such as RA, over time. The combination of rilonacept and azathioprine for treating RA has limited evidence, emphasizing the need for further research in this area.
Abstract 19164: The Role of Klf6 in Hypertensive Inflammation
Authors: Haynes Alexandria P , Ertuglu Lale A , Pitzer Mutchler Ashley , Sheng Quanhu , Saleem Mohammad , Kirabo Annet
Published: November 2023

Salt-sensitivity of blood pressure (SSBP) is a major risk factor for cardiovascular morbidity and mortality in people with or without hypertension. We previously found that oxidative lipid protein modification via NADPH oxidase in antigen presenting cells (APCs) contributes to SSBP but the underlying mechanisms are not known. HIF1α, which codes glycolytic enzymes in APCs enhances expression of Kruppel like factor 6 (KLF6), promoting expression of PDGFB which binds to the PDGFB receptor to activate NADPH oxidase, leading to increased oxidative stress and activation of mTOR. We hypothesize that HIF2α contributes to SSBP through activating NADPH oxidase by enhancing KLF6. To test this hypothesis, we isolated monocytes from human participants (N =11) and treated them with either high (190 mMol/L) or normal (150 mMol/L) Na+ in vitro for 72 hours and subsequently performed bulk RNA sequencing. We found that elevated sodium increases expression of HIFα (16437 ± 1810 vs. 42233 ± 6282, p = 2.28E-05) and KLF6 (9058 ± 584.3 vs. 12817 ± 1108, p = 0.6768). Interestingly, while the PDGFB receptor was upregulated by elevated sodium ( 21.18 ± 4.600 vs. 566.3 ± 205.3, p = 3.91E-13), the ligand PDGFB was downregulated (1249 ± 215.9 vs. 610.5 ± 118.2, p = 6.11E-04). In additional experiments, we performed single cell transcriptomic analysis in on immune cells of people phenotyped for SSBP. We found that in monocytes, as salt goes up with blood pressure so does the expression of KLF6 (r = 0.3773, p = 0.3561), PDGFB (r = 0.5604, p = 0.1485), and PDGFB receptor (r = 0.4436, p = 0.2709). Our data demonstrate the HIF1α-KLF6 pathway contributes to inflammation and SSBP.
Abstract 19166: Activity Level and Causes of Sudden Death: From the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death (POST SCD) Study
Authors: Kinkead Brielle , Eik David , Yee Matthew , Refaat Marwan M , Devinsky Orrin , Nakasuka Kosuke , Connolly Andrew , Moffatt Ellen , Tseng Zian H
Published: November 2023

Introduction:
Level of activity has a reported association with sudden death, but cardiac causes are presumed by convention. We investigated association between activity level and causes of presumed SCD (pSCD) in the San Francisco POstmortem Systematic InvesTigation of Sudden Cardiac Death (POST SCD) Study.

Methods:
POST SCD is a prospective cohort study using autopsy, clinical records, and toxicology to adjudicate arrhythmic (potentially rescuable with implantable defibrillator) or non-arrhythmic (e.g., tamponade, overdose) causes among pSCDs (WHO defined) 18-90 years in San Francisco. We included all incident cases from 2/1/11-3/1/14 (n=525) and incident cases approximately every 3rd day from 3/1/14-12/31/21 (n=358). Activity level at time of pSCD was determined by forensic investigator reports. For unwitnessed deaths, activity level was inferred based on time of arrest and location found. Activity level was classified as: sleep, recently awoke (<10 min before death), awake with no activity (e.g., sitting), mild/moderate (e.g., bathing, feeding, walking), and rigorous (e.g., strenuous activity, sexual activity).

Results:
Of the total 883 pSCDs (mean 60 years, 73% male), 247 (28%) were sleeping, and 516 (58%) were awake at time of event. Cases with unclear circumstances (n=120, 14%) were excluded from analysis. Sleep was associated with non-cardiac cause of death (p=.01), specifically SUDEP (p=.02) and occult overdose (p<.001). Wakefulness was associated with SAD (p=0.005), pulmonary embolism (p=.007), and vascular damage (p=.004) (Table). Nearly all cases engaging in rigorous activity at time of death (n=32) were SADs (31/32, 97%) and male (29/32, 91%).

Conclusions:
Most sudden deaths in this 11-year countywide postmortem study occurred during wakefulness. Sleep was associated with non-arrhythmic cause (specifically SUDEP and occult overdose), while wakefulness and rigorous activity were associated with arrhythmic cause of sudden death.