bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12883: Trends in Clinical Characteristics and Mortality in STEMI Patients Over Two Decades: Insights From the Midwest STEMI Consortium
Authors: Yildiz Mehmet , Kompella Divya , Okeson Brynn , Patel Kirtan , Pico Madison , Chambers Jenny , Aguirre Frank , Aziz Dalia , Garberich Ross , Jollis James , Garcia Santiago A , Sharkey Scott W , Henry Timothy D , QUESADA ODAYME
Published: June 2023

Introduction:
The past two decades have witnessed the evolution of percutaneous intervention technologies, advancements in post-STEMI cardiac care, and initiatives to improve STEMI systems of care. We aimed to explore the impact on STEMI management and prognosis in well-established regional STEMI systems.

Methods:
We examined the trends in clinical characteristics, management, and mortality in 12,879 consecutive STEMI patients between the periods of 2003-2009 (n=4,159) and 2010-2020 (n=8,720) using the Midwest STEMI Consortium; which consists of regional and tertiary STEMI centers with standardized STEMI protocols.

Results:
In 2010-2020, patients were older, more frequently female, and with a higher prevalence of previous MI, hypertension, dyslipidemia, and diabetes compared with the 2003-2009 period. In 2010-2020, patients were more likely to be treated with PCI, had shorter reperfusion times, and were more likely to receive guideline-directed medical therapy (GDMT) at discharge. Out-of-hospital cardiac arrest (OHCA) was more frequent in the 2010-2020 period (8.7% vs 10%, p=0.025), while the rate of cardiogenic shock was similar. In-hospital mortality was higher in the 2010-2020 period (4.7% vs 5.6%, p=0.037); while the post-discharge to 1-year mortality was lower (5.8% vs 4.4%, p=0.053)
(Table).

Conclusions:
In a well-established consortium of regional STEMI systems, the patient population has become at higher risk but STEMI management has improved with higher PCI rates, lower reperfusion time, and higher rates of GDMT, leading to lower post-discharge to 1-year mortality risk. In-hospital mortality risk was higher in the 2010-2020 period likely related to a higher cardiovascular risk profile, in particular, the increased number of OHCA in the last decade.
Abstract 12892: Cumulative Weight, Adipokines, and Hypertension
Authors: Broni Eric K , Michos Erin D , Zhang Sui , Echouffo Tcheugui Justin B , Florido Roberta , NAMBI VIJAY , Abushamat Layla , Post Wendy S , Gerstenblith Gary , Blumenthal Roger , Hoogeveen Ron C , Ballantyne Christie M , Coresh Josef , Selvin Elizabeth , Ndumele Chiadi E
Published: June 2023

Background
:
Chronic obesity is a major risk factor for hypertension, and obesity-associated hypertension is often difficult to control. Adipokines have vascular effects, but the degree to which they mediate the association between chronic obesity and hypertension is unknown.

Methods:
We conducted a cross-sectional analysis of 10,842 ARIC participants who attended Visit 3 (1993-95) with self-reported BMI at age 25 and measured BMI at visits 1 to 3 (each 3 years apart). We calculated cumulative excess BMI years by centering BMI at 25 kg/m
2
at each time point and multiplying the mean BMI by the duration in years from age 25 to Visit 3. We categorized cumulative excess BMI years by quartiles. Plasma adipokines (leptin, adiponectin) were measured at Visit 3. Prevalent hypertension at Visit 3 was defined as blood pressure ≥130/80mmHg or hypertension medication use. We used linear regression to assess associations between cumulative BMI quartiles and adipokines (log transformed). We used logistic regression to assess the association of cumulative BMI with prevalent hypertension and the extent to which adipokines mediate this relationship.

Results:
Higher quartiles of cumulative excess BMI years were associated with lower adiponectin and higher leptin levels (both p<0.001). Higher cumulative excess BMI years was strongly associated with hypertension (OR 2.52 [95% CI 2.21, 2.87], for top vs bottom quartile). Adiponectin partially mediated the association of cumulative excess BMI years with hypertension by 7% (OR for top quartile decreased from 2.52 to 2.41), leptin mediated the association by 18% (OR decreased from 2.52 to 2.24), and the combination of adiponectin and leptin mediated the association by 22% (OR decreased from 2.52 to 2.18) (
Table
).

Conclusion:
Adipokines may partially mediate the association of long-term excess adiposity with hypertension. Targeting adipokines may have therapeutic value in managing hypertension in those with chronic obesity.
Abstract 12998: Incidence, Complications, and Outcomes of High Degree Atrioventricular Block in Patients With Sarcoidosis
Authors: Niroula urza , Mir Tanveer , Hussain Tanveer , Qureshi Waqas , Shanah Layla , Khan Muhammad S , Uddin Mohammed , Tahir Hamza , Maturi Bhanu , Parajuli Tilachan
Published: June 2023

Introduction:
High degree atrioventricular block (AV block) is known to occur in patients with sarcoidosis. The incidence, complications and outcomes of high degree AVB in sarcoidosis patient is unknown. We aimed to analyze a national database to evaluate the epidemiological characteristics of AVB in sarcoidosis patients.
Method:
We included 110,264 sarcoidosis adult patients (age ≥18 years) hospitalized in 2019 from the Nationwide Readmission Database (NRD). Baseline demographics, comorbidities, and outcomes were identified using International Classification of Diseases (ICD) codes. High degree AVB was defined as Mobitz type II and complete heart block.

Results:
Of the total, 2336 (2.1%) sarcoidosis patients (mean age 61.0 ± 14.0 years and 52.8% females) were admitted with AVB. Of these, 71 (3.02%) patients died in the AVB group and 2691(2.49%) in the non AVB group (p >0.05). Complications were noted to be higher in AVB group vs. non AVB group (34.9% vs. 28.5%) but was not significantly associated with AVB (OR 1.03, CI (0.87- 1.23), p=0.7). The commonest complications were acute kidney injury (26.1% vs. 21.4%), cardiac arrest (2.64% vs 0.84%) and device related infection (1.89% vs 0.33%) that were significantly more than non AVB group with p<0.05. The cost of index hospitalization was higher for patients with AVB, but the length of stay was similar. The readmission rates or mortality is not associated with diagnosis of AVB on presentation.

Conclusion:
In hospitalized sarcoidosis patients, high degree AVB was not associated with increased risk of mortality or readmissions but with higher cost of hospitalization. In these patients, cardiac risk factors were associated with complications.
Abstract 13056: Evaluation of Stable Angina by Coronary Computed Tomographic Angiography versus Standard of Care: A Systematic Review and Meta-Analysis
Authors: Palicherla Anirudh , Ismayl Mahmoud , Thandra Abhishek , Shaikh Kashif
Published: June 2023

Introduction:
There has been growing evidence comparing Coronary Computed Tomography Angiography (CCTA) versus the standard of care(SOC) in patients with suspected stable coronary artery disease (CAD). We aimed to perform a systematic review and meta-analysis to compare CCTA versus SOC in patients with stable CAD.

Methods:
We searched multiple databases for randomized controlled trials (RCTs) comparing CCTA with SOC with various functional testing approaches for the evaluation of stable CAD. We used a random-effects model to calculate risk ratios (RRs) with 95% confidence intervals (CIs). Outcomes included all-cause mortality, myocardial infarction (MI), hospitalization for unstable angina (UA), invasive angiography, revascularization, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG).

Results:
We identified 6 RCTs with a total of 19,881 patients with stable CAD, of which 9,995 underwent CCTA and 9,886 underwent UC. There were no significant differences between CCTA and SOC in terms of all-cause mortality (RR: 0.91; 95% CI: 0.70-1.19; p=0.64), MI (RR: 0.78; 95% CI: 0.58-1.05; p=0.70), hospitalizations for UA (RR: 1.20; 95% CI: 0.95-1.51;p=0.64), invasive angiography (RR: 0.11; 95% CI: 0.32-1.61; p<0.00001), revascularization (RR:1.25; 95% CI: 0.83-1.89; p<0.00001), PCI (RR: 1.20; 95% CI: 0.78-1.85; p<0.00001), and CABG rates (RR: 0.89; 95% CI: 0.530-1.49; p=0.0003).

Conclusions:
In patients with stable CAD, CCTA is associated with similar outcomes compared to the usual standard of care. Given its non-invasive nature and capability to evaluate atherosclerotic plaque burden, CCTA may be preferred as an initial strategy for the evaluation of patients with stable CAD.
Abstract 13062: In vivo Knockdown of Proapoptotic Mir-320 Restores Cardiac Function and Angiogenesis in a Mouse Model of Type 2 Diabetes
Authors: Ghosh Nilanjan , Fenton Sonya , Chatterjee Aniruddha , Schwenke Daryl , Katare Rajesh
Published: June 2023

Background:
Non-ischemic diabetic heart disease (NiDHD) is characterised by diastolic dysfunction and decreased or preserved systolic function, eventually resulting in heart failure. The fundamental mechanisms leading to NiDHD are still not known. microRNAs (miRNAs) plays a significant role in the development of NiDHD.

Objective:
To investigate the pathological role of cardiomyocyte enriched pro-apoptotic miR-320 in the development of NiDHD and to determine if therapeutic knockdown of miR-320 can restore impaired cardiac function and angiogenesis in the diabetic heart.

Methods and Results:
Cardiac tissue were collected from type-2 diabetic individuals undergoing cardiac surgery showed marked upregulation of miR-320, which was associated with downregulation of its direct target pro-survival insulin growth factor-1 (IGF-1) and anti-apoptotic protein Bcl-2. Analysis of cardiac tissue samples collected from type 2 diabetic mice (BKS.Cg-m+/+Leprdb/J) every 4wks, from 8 to 32wks of age showed activation of miR-320 and downregulation of IGF-1 at the later stages of diabetes. To determine if therapeutic knockdown of miR-320 is beneficial, high glucose cultured adult cardiomyocytes were treated with either locked nucleic acid (LNA) anti-precursor (pre)-miR-320 or scrambled (Scr) sequence. Results showed that LNA-anti-pre-320 significantly restored IGF-1 expression and reduced apoptotic cells death (3.1±05 in Scr vs 1.3±0.6 in LNA-anti-pre-320, P<0.01). Finally, to confirm if the effect can be translated
in vivo
, 24 weeks old type 2 diabetic mice with established systolic dysfunction were injected with LNA-anti-pre-320 once a week for 4wks. Echocardiography confirmed significant restoration of diastolic function and partial restoration of systolic function. Molecular analysis showed marked reduction in miR-320 expression, which was associated with recovery of IGF-1 and Bcl-2. Further, histological analysis confirmed improved angiogenesis and reduced fibrosis in the LNA-anti-pre-320 treated group.

Conclusion:
miR-320 is a late responding miRNA that aggravates apoptosis and cardiac dysfunction in diabetic heart, and that therapeutic knockdown of miR-320 is beneficial in partially restoring the deteriorated cardiac function.
Abstract 131: Perceived Exertion And Physical Demand Of Performing 10-minutes Of Compression-only CPR
Authors: Flickinger Kate , DeMaio Ryann , Prescott Peter , Weissman Alexandra , Salcido David D , Coppler Patrick J , Ratay Cecelia R , Nagle Elizabeth , Rittenberger Jon , Goss Fredric , Callaway Clifton W , Menegazzi James J
Published: June 2023

Cardiopulmonary resuscitation (CPR) is physically demanding and must also be performed under emotional distress. Most cardiac arrests (CA) occur at home, making it likely that only one rescuer is available to perform CPR until emergency medical services (EMS) or other lay rescuers arrive.

We performed a study to quantify the physical exertion required of lay-providers performing compression-only CPR for 10 minutes both with (WFB) and without (WOFB) real-time CPR quality feedback.

We recruited healthy, CPR certified lay individuals to perform 10-minute rounds of CPR on two occasions: once WFB and once WOFB. We collected heart rate (HR), oxygen consumption (VO
2
), and rating of perceived exertion (RPE) at baseline and throughout each round of CPR and collected capillary lactate and blood pressures pre- and post-CPR. We used Kruskal Wallis, Wilcoxon signed rank and rank sum tests to compare changes in measures during CPR.

Participants were 15 females and 11 males, age 25 (IQR 22-37). All measures except for diastolic blood pressure, significantly changed over time. Systolic blood pressure increased both WFB (mean difference (MD) 8mmHg; 95% CI 12-5) and WOFB (MD 8mmHg; 95% CI 12-3). VO
2
and HR increased over time, but peak VO
2
and HR did not differ by group. RPE significantly increased WFB and WOFB (WFB MD 8; 95% CI 10-7; WOFB MD 8; 95% CI 9-7) WFB and WOFB, with females reporting a higher RPE immediately post-CPR WFB than males (MD 2; 95% CI 5-1). Lactate increased from baseline immediately post (WFB MD 2.3mmol/L; 95% CI 0.9-3.7; WOFB MD 1.8mmol/L; 95%CI 2.6-1) and 5-minutes post CPR (WFB MD 0.8mmol/L; 95% CI 2.3-0.7; WOFB MD2.1 mmol/L; 95% CI 0.9-3.3).

CPR produces subjective and objective signs of strenuous exertion in both men and women. The presence of feedback does not alter physiologic response to prolonged CPR. However, females reported higher RPEs when performing CPR WFB, despite no significant difference in physiologic response.
Abstract 13267: Angina Burden and Coronary Vascular Function in Women With Ischemia and No Obstructive Coronary Arteries—Role of Oxygenation-Sensitive Cardiovascular Magnetic Resonance Imaging
Authors: Visch Julia , Luu Judy M , Hillier Elizabeth , Elharram Malik , White James , Anderson Todd , Friedrich Matthias , Pilote Louise
Published: June 2023

Introduction:
Patients with ischemia and no obstructive coronary arteries (INOCA) often have coronary microvascular dysfunction (CMD). An association between higher angina burden (lower Seattle Angina Questionnaire [SAQ] scores) and increased severity of CMD has previously been reported. Oxygenation-Sensitive Cardiovascular Magnetic Resonance (OS-CMR) is a novel approach that can potentially evaluate CMD. To date, the relationship between angina burden and OS-CMR biomarkers has not been elucidated.

Methods:
We investigated the association between angina burden, quantified by the mean and 5 individual components of the SAQ, with measures of myocardial oxygenation, using OS-CMR. More severe CMD is reflected by a decreased % signal intensity (SI) change after hyperventilation (Breathing-enhanced Myocardial REserve, B-MORE), calculated by [(Hyperventilation - Breath Hold)/Breath Hold] x 100%. Univariable linear regression analysis was used to investigate the associations.

Results:
In 44 women with INOCA (mean age 55.1±0.9 years), B-MORE was 5.0±1.4% (Table). Several components of the SAQ were associated with OS-CMR measures of CMD [physical limitation (R
2
=0.281, Beta=0.530, p=0.042), angina frequency (R
2
=0.216, Beta=0.465, p=0.039), disease perception (R
2
=0.254, Beta=0.504, p=0.024), and the mean overall SAQ (R
2
=0.285, Beta=0.534, p=0.015)] (Panel Figure).

Conclusion:
In women with INOCA, angina burden is associated with coronary vascular function, as assessed by OS-CMR. Therefore, this novel approach may provide objective information to detect the presence of CMD.
Abstract 13316: Multi-Ancestry Genome-Wide Association Analysis in 1.9 Million Individuals Identifies 49 New Genetic Loci for Heart Failure and Related Subtypes
Authors: Henry Albert , Lumbers Tom ,   HERMES Consortium
Published: June 2023

Introduction:
Characterization of the genetic etiology of heart failure (HF) provides an opportunitiy to advance understanding of causal human biology and to develop genomic tools for prediction and patient stratification. We conducted a multi-ancestry genome-wide association meta-analysis of HF and related subtypes in 1.9 million individuals.

Methods:
We investigated 10,199,961 common genetic variants for association with all-cause HF (145,795 cases); non-ischemic HF, defined as the absence of antecedent myocardial infarction and abnormal loading conditions (44,030 cases); and non-ischemic HF stratified by left ventricular ejection fraction (LVEF) (5,407 cases of LVEF <50% and 3,846 cases of LVEF 50%). By synthesizing evidence from functionally-informed fine-mapping, in silico gene prioritization, and multi-tissue transcriptome-wide association analysis, we prioritized likely causal variants, effector genes, and tissues for HF. We tested for enrichment of genes linked to Mendelian disorders within genomic loci for HF and assessed the genetic correlation of HF-related traits and their causal inter-relationships using Mendelian randomization.

Results:
We identified 56 independent genomic loci, including 39 novel, associated with all-cause HF; and additional 10 novel independent genomic loci among non-ischemic HF subtypes at P < 5 x 10-8. Genomic loci for HF were enriched for genes associated with Mendelian disorders of cardiomyopathy (Padjusted = 0.01) and arrhythmia (Padjusted = 0.0006). In 30 / 56 loci for all-cause HF, functionally-informed fine-mapping identified 5 or fewer likely causal variants. Genetically predicted expression levels of 266 genes across 49 human tissues were associated with HF at a false discovery rate <1%, 95 (36%) of which were also identified in heart tissue-specific analysis. Genetic correlation and causal associations were detected between upstream risk factors and traits of cardiac structure and function, yielding new insights into HF endophenotype relationships.

Conclusion:
These findings extend our understanding of the etiology of the HF syndrome and provide new opportunities to inform the development of new therapeutic strategies.
Abstract 13321: Navigating a Device Post-Approval Study During Covid-19
Authors: Nair Devi , Garner John , Ciuffo Allen , MacGregor John , Rhodes Troy , Shah Anand , Hamdan Firas , Pickett Robert , Ostrom Matthew , Hopper Donald , Wold Nicholas , Kantor Gena , Tabereaux Paul
Published: June 2023

Background:
The conduct of clinical trials during COVID-19 created challenges to ensuring access to clinical trials, healthy clinical teams, and patients. Innovative methods such as remote patient follow-up and monitoring visits can lead to successful completion of device trials.

Objective:
The INGEVITY+ Active Fixation Pace/Sense Lead Study examined the safety/ efficacy of the INGEVITY+ Lead in a prospective, non-randomized, multicenter, post-approval study.

Methods:
Subjects met indications for a pacing device with INGEVITY+ leads implanted in the RA and RV. The primary safety endpoint was the 3-month lead-related complication-free (LRC-free) rate. The primary efficacy endpoint evaluated the 3-month pacing capture threshold with the secondary efficacy endpoint evaluating the other lead-related electrical parameters. Implanter experience was assessed. Telephone visits with LATITUDE remote transmission of lead measurement data and remote monitoring visits were allowed.

Results:
A total of 201 leads were evaluated in 101 subjects, 46.8% female with a mean age of 73.2 years, at 13 centers in the United States. The study took 6.8 months, with a median follow-up of 3.4 months. The 3-month follow-up was completed by 98% of subjects, of which 36% were remote. A total of 98% of monitoring visits were done remotely. The study met all primary and secondary endpoints. The LRC-free rate through 3-months was 98.5% (lower CL 95.4%). Three leads were repositioned and reimplanted; two were RA dislodgements, and one was a RA perforation and hemothorax requiring thoracentesis. The pacing capture threshold was ≤ 2V in 98.9% of subjects with a mean of 0.77 V at 0.4-ms pulse width, mean pacing impedance of 712 ohms, and a median P-wave amplitude of 4.3 mV, and median R-wave amplitude of 15.9 mV at 3-months. No helix performance issues were reported. The mean turn count for helix extension was 6.7 and retraction was 7.6. More than 85% of physicians rated the lead as ‘very good’ or higher on all aspects of lead handling.

Conclusions:
The INGEVITY+ Lead was found to be safe and effective with a very favorable implant experience. This study was entirely conducted successfully during COVID-19 with remote follow-up and monitoring visits, and nearly half of the subjects were females.
Abstract 13351: Firefighter Coronary Atherosclerotic Burden Compared to Non-Firefighters
Authors: Alalawi Luay , Manubolu Venkat S , Verghese Dhiran , Aldana-Bitar Jairo , Kinninger April , Ghanem Ahmed K , Ahmad Khadije , Shafter Ahmed , Al-Chokhachi Zahra , Golub Ilana , Johanis Amit , Roy Sion , Budoff Matthew
Published: June 2023

Introduction:
Cardiovascular (CV) disease is the leading cause of death for on-duty firefighters. According to the National Fire Protection Association (NFPA), 44% of all fatalities were due to sudden cardiac deaths, and 90% of which were due to coronary artery disease. Furthermore, firefighters are prone to occupational behaviors, conditions, and environmental exposures that may increase their adverse outcomes. In this study, we will attempt to explore the atherosclerotic differences between firefighters and non-firefighter individuals.

Methods:
302 firefighters from the Los Angeles fire department who underwent coronary computed tomography angiogram from 2008 to 2021 were matched 1:1 for age, gender, race, diabetes mellitus (DM), hyperlipidemia (HLD), hypertension (HTN), and past smoking to a control cohort for comparison of semi-quantitative coronary plaque burden. Each coronary segment was assessed by a semi-quantify plaque severity (0 for no plaque, 1 for minimal or mild, 2 for moderate, 3 for severe) and luminal stenosis (0: none, 1: <30%, 2: 30-49%, 3: 50-69%, 4: 70-99% and 5:100%). The total plaque severity score (TPS) was calculated by the sum of the individual segment plaque severity score. The total segment stenosis score (TSS) was calculated by adding all the individual segment stenosis score (SSS). Segment involvement score (SIS) was calculated by summing the total number of coronary segments with plaque.

Results:
Mean (SD) age was 51.3 (6.6); 2% were diabetic; 34% had hyperlipidemia; 19% were hypertensive; 10% were prior smokers in each cohort. The Fire Fighter cohort had significantly higher coronary calcium scores (mean 42.5 vs 12); p<0.0001, TPS at 3 (IQR (1,6) vs 2 (IQR (0,5)); p<0.0001, TSS 3 (IQR (1,5) vs 2 (IQR (0,5)); p<0.0001 , and SIS 2 (IQR (1,4) vs 2 (IQR (0,4)); p<0.0001.

Conclusions:
After matching for age, gender, race, DM, HTN, HLD, and past smoking. Firefighters had more plaque burden, more stenosis, and more diffuse disease when compared to nonfirefighters, illustrating the occupational effects on the atherosclerotic process
Abstract 13399: A Case of Propofol-Induced Takotsubo Cardiomyopathy
Authors: Aina Deborah A , Nicholson Chad , Small Delano
Published: June 2023

Introduction:
Takotsubo syndrome (TS) is a transient cardiomyopathy characterized by an apical ballooning appearance, mimicking a myocardial infarction. Stress-induced catecholamine excess is the best studied hypothesis. There have been few reported cases of TS following induction of anesthesia. This is the first case that describes propofol as an inciting factor in the development of TS.

Case report:
A 75-year old male with history of COPD, recurrent pneumothorax, pharyngeal cancer, and no prior cardiac history, presented with dyspnea. Chest x-ray revealed a right-sided pneumothorax. Plan was to proceed with thoracoscopy and talc pleurodesis. He underwent induction of general anesthesia with propofol. Following induction, he went into asystole, requiring a round of CPR prior to ROSC and transfer to the ICU. Troponin was elevated at 1.12. EKG revealed diffuse ST-segment elevation. ECHO showed EF 15-20%, with severe global hypokinesis, a hyperdynamic left ventricle at the base, concerning for TS (Figure 1). Repeat ECHO eight days later, revealed a recovered EF of 70-75%. The most likely diagnosis was TS.

Discussion:
This case identifies propofol as an inciting factor in the development of TS during the induction of general anesthesia. Propofol is a sedative-hypnotic, used in the induction and maintenance of general anesthesia. It works by decreasing the dissociation from GABA receptors, leading to an inhibitory effect on wakefulness. However, it also adversely acts at the cellular level as a calcium antagonist, reducing vascular tone, leading to hypotension and depression of myocardial contractility. We postulate that the inhibitory effects of propofol on the cardiovascular system, likely contributed to the development of TS in our patient.

Conclusion:
In conclusion, use of propofol during the induction process may be an important risk factor in the development of TS. This is an important consideration when choosing induction agents, in high risk patients.
Abstract 13422: Sotagliflozin, a Dual SGLT-1/2 Inhibitor, Modulated Expression of Endothelial Proteins That Inhibit Reactive Oxygen Species During Inflammation Compared With Empagliflozin
Authors: Sherratt Samuel , Libby Peter , Bhatt Deepak L , Mason Preston
Published: June 2023

Background:
Reactive oxygen species (ROS) generated during endothelial cell (EC) dysfunction contributes to progression of atherosclerosis. The SGLT1/2 inhibitor sotagliflozin (sota) reduced atherothrombotic events and hospitalization for worsening heart failure in patients with diabetes (SCORED, SOLOIST). Unlike selective SGLT2 inhibitors, sotagliflozin significantly reduced ischemic events, including myocardial infarction and stroke. We compared the effects of sota and empagliflozin (empa) on expression of ROS signaling proteins in human vein ECs (HUVECs) challenged with interleukin-6 (IL-6) or lipopolysaccharide (LPS).

Methods:
HUVECs were treated with sota or empa (100 nM) for 30 minutes and the challenged with IL-6 (12 ng/mL) or LPS (100 ng/mL) for 24 hours. Global proteomic analysis was performed using LC/MS to measure relative expression levels of >1,000 proteins. Only significant (p<0.05) changes in expression between treatment groups >1-fold were included in gene set enrichment analysis (GSEA) of biological pathways.

Results:
Sota significantly changed expression of 166 and 274 proteins in ECs challenged with IL-6 and LPS, respectively. Empa significantly modulated fewer proteins - 122 and 93 proteins - following challenge with IL-6 and LPS, respectively. GSEA revealed that sota, not empa, modulated proteins related to ROS detoxification within the “cellular response to oxidative stress” pathway (GO:0034599) compared to both IL-6 and LPS (pathway adjusted p-values = 0.0016 and 0.036, respectively). Within this pathway, sota increased expression of peroxiredoxin (PRDX) 5 and PRDX6 (1.2 and 1.1-fold) and glutathione peroxidase-1 (GPX1, 1.1-fold) relative to IL-6 alone. Relative to LPS, sota decreased expression GPX1 (1.2-fold), PRDX1 (1.1-fold), and increased thioredoxin (1.1-fold). None of these proteins were modulated significantly by empa.

Conclusions:
Sota significantly modulated expression of proteins linked to ROS detoxification and signaling in human ECs during inflammation compared to a selective SGLT2 inhibitor. These favorable effects of dual SGLT1/2 inhibition may have implications for inflammation and reduced atherothrombotic risk as demonstrated in outcome trials.
Abstract 13462: Valve-in-Valve Transcatheter Mitral Valve Replacement versus Redo Surgical Mitral Valve Replacement for Degenerated Bioprosthetic Valves: A Systematic Review and Meta-Analysis
Authors: Ismayl Mahmoud , Abbasi Muhannad , Zaalouk Mostafa , Aboeata Ahmed S , Anavekar Nandan S , Goldsweig Andrew M
Published: June 2023

Introduction:
Valve-in-valve transcatheter mitral valve replacement (ViV-TMVR) and redo surgical mitral valve replacement (redo-SMVR) are two treatment strategies for patients with bioprosthetic mitral valve dysfunction. We conducted a systematic review and meta-analysis to compare the outcomes of ViV-TMVR versus redo-SMVR.

Methods:
We searched PubMed, EMBASE, Cochrane, and Google Scholar for studies comparing outcomes of ViV-TMVR versus redo-SMVR in degenerated bioprosthetic mitral valves. We used a random effects model to calculate risk ratios (RRs) with 95% confidence intervals (CIs). Outcomes included in-hospital, 30-day, 1-year, and 2-year mortality, stroke, bleeding and vascular complications, acute kidney injury (AKI), arrhythmias, and hospital length of stay (LOS).

Results:
Six observational studies with a total of 1,339 subjects were included. Median follow-up was 2 years. Compared to redo-SMVR, ViV-TMVR was associated with significantly lower in-hospital (RR 0.42; 95% CI 0.25-0.70; p=0.001) and 30-day mortality (RR 0.49; 95% CI 0.24-0.98; p=0.04) but similar 1-year (RR 0.97; 95% CI 0.64-1.47; p=0.89) and 2-year mortality (RR 1.14; 95% CI 0.71-1.81; p=0.59). Stroke, bleeding, AKI, and arrhythmias were less frequent and hospital LOS was shorter with ViV-TMVR, however vascular complications were similar between both strategies.

Conclusion:
In patients with degenerated bioprosthetic mitral valves, ViV-TMVR is associated with better outcomes compared to redo-SMVR including lower in-hospital and 30-day mortality, lower complication rates, and shorter hospital LOS. Given these findings and the ongoing advances in transcatheter therapeutics, ViV-TMVR may be preferred over redo-SMVR, particularly in individuals at intermediate-to-high surgical risk.
Abstract 13518: Augmenting SOD2 Levels in
Apoe
-/-
Mice With Peptide-mRNA Nanoparticles Preserves Atherosclerotic Plaque Stability in Advanced Atherosclerosis
Authors: Vendrov Aleksandr E , Lozhkin Andrey , Pan Hua , Wickline Samuel A , Runge Marschall , Madamanchi Nageswara R
Published: June 2023

Erosion or rupture of the advanced atherosclerotic plaque is the leading cause of atherosclerosis complications such as acute coronary syndrome and stroke. Atherosclerotic plaques in aging hypercholesterolemic mice have decreased SOD2 levels and increased mitochondrial oxidative stress, which leads to cell apoptosis, necrotic core expansion, and fibrous cap thinning and rupture. We hypothesized that increasing SOD2 expression in advanced atherosclerotic plaque cells in mice using mRNA polyplex would protect mitochondria from oxidative damage and preserve plaque stability. Macrophages isolated from
Sod2
+/-
mice treated with amphipathic cationic peptide p5RHH:
Sod2
mRNA polyplexes had markedly increased levels of
Sod2
mRNA and mitochondrial SOD2 (p<0.01), higher SOD activity, which resulted in lower levels of mitochondrial and cellular reactive oxygen species (ROS) and improved mitochondrial function. RNA-Seq analysis showed that macrophages treated with
Sod2
nanoplexes had broadly decreased inflammatory cytokines and immune activation pathways. In
Apoe
-/-
mice, atherosclerotic lesions with vulnerable plaque features were induced in the carotid artery by placing a perivascular collar over the carotid artery and 4-months Western diet. Mice were treated for 4 weeks with saline or with 0.5 mg/kg p5RHH:
Sod2
mRNA polyplexes which selectively accumulated in atherosclerotic lesion macrophages. The carotid plaques of the mice treated with
Sod2
mRNA differed significantly from the plaques of the control
Apoe
-/-
mice by higher SOD2 expression, lower mitochondrial ROS and oxidative DNA damage, and reduced expression of CCL2, IL1, IL6, MMP 2 and 9 (p<0.01).
Sod2
polyplexes-treated mouse plaques exhibited 25% fewer inflammatory macrophages (p<0.01) and 98% more smooth muscle cells (p<0.001) with a reduced lipid core, preserved fibromuscular cap, and decreased plaque vulnerability index (p<0.05). The results suggest that selective overexpression of
Sod2
in plaque macrophages using nanoplexes reduces mitochondrial stress and preserves plaque stability without adverse effects. Using nanoparticle-based mRNA therapeutics to modulate plaque morphology has great potential in the prevention and treatment of atherosclerosis complications.
Abstract 13551: Non-Invasive Assessment of Systemic Microvascular Function in Patients With Severe Aortic Stenosis Pre- and Post- Transcatheter Aortic Valve Intervention
Authors: Mailey Jonathan A , Brennan Paul , Moore Julie , Jing Min , McLaughlin James , Nesbit Andrew , Moore Tara , Spence Mark S
Published: June 2023

Background:
Aortic stenosis (AS) is associated with pathophysiological changes in both left ventricular and coronary microvascular structure and function. The treatment of AS with transcatheter aortic valve replacement (TAVR) has been associated with improvements in invasive indices of coronary microvascular function. This study sought to address whether systemic microvascular dysfunction was present in patients with AS and if microvascular function was altered by treatment of aortic stenosis with TAVR. The conjunctival microcirculation was used as the site for the non-invasive assessment of systemic microvascular function.

Methods:
Patients undergoing TAVR for the treatment of severe AS were compared to a cohort of age- and sex-matched controls without valvular heart disease. Conjunctival vascular imaging was performed in all subjects using a previously validated combination of a smartphone and slit-lamp biomicroscope. This technique allowed measurement of vessel diameter and other indices of microvascular function by tracking erythrocyte motion. Conjunctival hemodynamics were compared pre- and post-TAVR, in addition to between the severe AS and control cohorts.

Results:
A total of 165 patients were included (90 severe AS and 75 controls). Baseline characteristics were well matched between groups. In comparison to the control cohort, arteriole axial (Va) and cross-sectional velocity (Vcs) were significantly lower in females with AS (Va severe AS 0.53 ± 0.11mm/s vs control 0.59 ± 0.12mm/s, p=0.047; Vcs severe AS 0.38 ± 0.07mm/s vs control 0.41 ± 0.08mm/s, p=0.043), but not in males (Va severe AS 0.61 ± 0.11mm/s vs control 0.58 ± 0.10mm/s, p=0.19; Vcs severe AS 0.43 ± 0.08mm/s vs control 0.41 ± 0.07mm/s, p=0.20). Arteriole Va and Vcs significantly increased following TAVR in females (Va Pre-TAVR 0.52 ± 0.16mm/s vs post-TAVR 0.59 ± 0.15mm/s, p<0.001; Vcs Pre-TAVR 0.37 ± 0.11mm/s vs post-TAVR 0.42 ± 0.11mm/s, p<0.001).

Conclusion:
This study highlights sex-specific differences in conjunctival microvascular function in patients with severe AS. In this study TAVR resulted in significant improvements in conjunctival arteriolar V
a
and V
cs
. These findings are consistent with severe AS being a reversible cause of systemic microvascular dysfunction.
Abstract 13554: Effect of Positive Airway Pressure Therapy for Obstructive Sleep Apnea in Heart Failure Patients With Reduced Ejection Fraction - Implications for Healthcare Resource Utilization
Authors: Malhotra Atul , Cole Kate , Malik Anita , Pépin Jean-Louis , Sert Kuniyoshi Fatima H , Cistulli Peter , Benjafield Adam , Somers Virend K ,   on behalf of the medXcloud group
Published: June 2023

Introduction:
Obstructive sleep apnea (OSA) is common in heart failure, although the impact of OSA treatment remains unclear. We assessed the association between adherence to positive airway pressure (PAP) therapy and healthcare resource utilization in patients with OSA and heart failure with reduced ejection fraction (HFrEF).

Methods:
Administrative insurance claims data linked with objective PAP therapy usage data from patients with OSA and HFrEF were used to measure the association of PAP adherence and a composite clinical outcome of hospitalization and emergency room (ER) visits. US Medicare defines PAP compliance as usage of the device for at least 4 hours/night for 70% of nights in a consecutive 30-day period over 90 days. PAP adherent patients met these criteria for all 4 90-day periods, while PAP non-adherent patients did not meet these criteria for any 90-day period over one year. Propensity score methods were used to create well matched groups with differing PAP adherence levels.

Results:
The study cohort consisted of 3,182 eligible patients (69.9% male, mean age 59.7 years) of whom 39% were considered adherent to PAP therapy (29% intermediate-adherent, 31% non-adherent). In the year after PAP prescription, after propensity score matching, PAP adherent patients had fewer hospital visits than non-adherent patients, driven by a 24% reduction in ER visits for adherent patients (Table 1a). These results remained consistent with inverse probability weighting and furthermore showed there were no statistically significant differences between intermediate-adherent and non-adherent patients for any outcome (Table 1b).

Conclusions:
Treating OSA with PAP therapy in patients with HFrEF is associated with a reduction in the composite outcome of hospitalization and ER visits, driven primarily by a reduction in ER visits. Consistent adherence to PAP therapy is required to realize these benefits.
Abstract 13723: Uric Acid and Treatment With Empagliflozin in Heart Failure With Preserved Ejection Fraction: The EMPEROR-Preserved Trial
Authors: Doehner Wolfram ,   on behalf of the EMPEROR-Committees and Investigators
Published: June 2023

Background:
The sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin reduces CV death and hospitalization for HF (HHF) in patients with HF with preserved ejection fraction (HFpEF). Empagliflozin reduces serum uric acid (SUA), but the relevance of this effect in HFpEF is unclear.

Methods:
This post-hoc analysis of the EMPEROR-Preserved trial assessed the association between SUA and the composite primary outcome of CV death or hospitalization for worsening HF, its components and all-cause mortality (ACM) in 5,924 patients with HFpEF (98.9% of study cohort). We investigated effects of empagliflozin on SUA levels and hyperuricemic events (acute gout, gouty arthritis or initiation of anti-gout therapy), and on outcomes in relation to baseline SUA and the change in SUA levels

Results:
Hyperuricemia was prevalent in 49% of patients (male: 42%, female: 57%). Elevated SUA (highest tertile, mean SUA 8.8±1.4mg/dL) was associated with severity of HF and higher risk of HHF (first HHF: HR 1.42 [95%CI 1.08-1.86], recurrent HHF: HR 1.69 [95%CI 1.23-2.32], in comparison with the lowest tertile within the placebo group, both p<0.01). Elevated SUA was not associated with increased CV death and ACM. Empagliflozin reduced SUA at 4 weeks (vs. placebo: -1.0±0.03mg/dL, p<0.0001) and SUA remained lower throughout follow up. Empagliflozin reduced events of clinically relevant hyperuricemia by 38% (HR 0.62 [95%CI 0.51-0.76], p<0.0001). The benefit of empagliflozin on the primary endpoint was independent of baseline SUA (HR 0.79 [95%CI 0.69-0.90], p=0.0007) and absolute change in SUA at 4 weeks (HR 0.87 [95%CI 0.75-1.01, p=0.07] landmark analysis). The benefit of empagliflozin versus placebo on the rate of decline of eGFR and time to first renal composite outcome was consistent across SUA tertiles (p for interaction 0.92 and 0.89, respectively)

Conclusion:
Hyperuricemia is common in HFpEF and is an independent predictor of disease severity and increased risk of hospitalization. Empagliflozin induced a rapid, sustained reduction of SUA levels and clinical events related to hyperuricemia. The benefit of empagliflozin on the primary outcome in HFpEF was observed independently of SUA.
Abstract 13731: 30-Days Readmission Rate, Mortality and Health Care Burden Among Patients Who Underwent Transcatheter Mitral Valve Repair With Co-Existing Atrial Fibrillation
Authors: Fatuyi Michael , Udongwo Ndausung , egbujiobi tochukwu , Horoub Ali , El Hajj Nadine , Amoah Joseph , BANKEJESU NESTA , Williams-Idahagbon Fumilayo , Ajam Firas , Akinti Oluwasegun O , Kiss Daniel
Published: June 2023

Introduction:
Transcatheter mitral valve repair (TMVR) is a minimally invasive technique for the treatment of selected patients with symptomatic chronic moderate to severe mitral regurgitation (MR). Depending on the severity & chronicity of MR, there is left atrium remodeling in response to the volume overload, which contributes to the generation of atrial fibrillation (AF). Our study aimed to examine the 30-day readmission rates (30-DRr) among patients who underwent TMVR with co-existing AF in the United States.

Methods:
Using the 2017 National Readmission Database, we conducted a retrospective analysis of patient discharges with TMVR as a principal diagnosis and co-existing AF as a secondary diagnosis according to ICD-10 codes. Readmission was defined as the first admission to any hospital for any non-trauma diagnosis within 30 days of the index discharge. The primary outcome was 30-DRr, while secondary outcomes were readmission mortality rate, most common diagnoses for readmission, length of stay, hospitalization costs & patient charge.

Results:
A total of 3,242 Index admission with TMVR and AF; mean age 79.2years, & 53.3% male. In-hospital mortality rate was 2.46%, while all-cause readmission rate was 12%. Among this group of readmitted patients, the in-hospital mortality rate increased to 5.66% (aOR 2.38, adjusted p-value=0.009). The total hospital days associated with readmission were 2,244 days, with a total healthcare in-hospital economic burden of $6.24 million and total patient charge of 27 million. The most common diagnoses for readmission were hypertensive heart and chronic kidney disease with heart failure, hypertensive heart heart failure, Sepsis, AKI, Non-rheumatic MR &, AF, respectively.

Conclusions:
We observed among patient who underwent TMVR with co-existing AF, 1 in 8 was readmitted within 30-days with subsequent readmission associated with an increase in mortality and prolonged LOS, thus contributing to a significant economic burden.
Abstract 13940: Intra-Operative Findings With Massive Device-Related Thrombus After Percutaneous LAA Closure: Mechanistic Insights
Authors: Malik Kashif , Bai Rong , Vukomanovic Damir , Taase Alicia , Kitchell Eleanor , Skaria Rinku , Tung Roderick , Fang Kenith , Zawaneh Michael
Published: June 2023

Background:
Device related thrombus (DRT) has an observed incidence of ~4% after left atrial appendage closure (LAAC), of which the mechanism remains incompletely understood.

Objective:
To present and examine the intraoperative findings of 2 cases of massive DRT occurring late post LAAC device implantation and propose potential mechanisms for these rare complications.

Methods:
N/A

Results:
Patient 1 was a 75-year-old female with paroxysmal AF and CHA2DS2-VASc Score of 5 with Watchman implanted two years prior to presentation. She had completed 45 days of warfarin and ASA after implantation. She underwent elective open heart surgery for severe mitral valve regurgitation and moderate to severe aortic valve regurgitation. Large DRT (2x2cm) was diagnosed intraoperatively, which was treated with left atrial appendage and device resection. Patient 2 was a 75-year-old female with permanent AF and CHA2DS2-VASc Score of 5, who was referred for routine postimplant surveillance TEE. She had also completed 45 days of warfarin and ASA after implantation. A large DRT measuring 2 x 2 cm was noted. The patient was treated with warfarin and subsequently dabigatran with improvement in the size of thrombus on TEE. However, a gastrointestinal bleed led to the cessation of anticoagulation. Subsequent TEE demonstrated enlargement of massive DRT (3x2 cm). She was referred to cardiac surgery for thrombectomy and resection of the Watchman device and LAA.

Discussion/Conclusion:
In both cases, the intraoperative findings demonstrate well-seated LAAC without gross findings of malapposition or peri-device leaks. The central screw was visible without evidence of endothelialization in both cases (Figure 1). An exposed central screw could be a possible nidus for thrombus formation.
Abstract 13951: Sex Difference in Patients With Heart Failure: A Multicenter, Retrospective 8-year Observational Study
Authors: Chen Chun-Chao , Liu Ju-Chi , Hsu Min-Huei , Chiu Chun-Chih , Lin Jiunn-Lee
Published: June 2023

Introduction:
In real world, the difference of clinical characteristics and long-term outcomes between male and female patients (pts) with heart failure (HF) remained unclear.

Methods:
A total of 12,428 pts (6,518 men and 5,910 women) with first time HF hospitalization in Taipei Heart Institute HF cohort from 2011 to 2020 were analyzed. Baseline characteristics, echocardiogram, all-cause death, cardiovascular (CV) death and HF rehospitalization were assessed.

Results:
Female pts with HF hospitalization diagnosis were older than male (76.04 ± 13.43 vs. 71.20 ± 13.43 year-old respectively, p<0.0001), with higher prevalence of hypertension, diabetes and thyroid disease (70.74% vs. 65.02%, p<0.0001; 42.86% vs. 38.55%, p<0.0001; 9.81% vs. 5.25%, p<0.0001, respectively) but lower prevalence of ischemic heart disease, cerebrovascular disease and chronic obstructive lung disease compared with men (12.47% vs. 16.78%, p<0.0001; 3.91% vs. 6.31%, p<0.0001; 10.80% vs. 20.28%, p<0.0001, respectively). Also, higher proportion of significant chronic kidney disease (eGFR < 60 ml/min/1.73m
2
) was noted among female pts (p<0.0001). In echocardiography, more female pts had preserved left ventricular ejection fraction (LVEF) (LVEF >50%, female: 63.84% and male: 51.60%, p<0.0001), with greater LV mass index (female, 90.38 ± 35.03 vs. male, 84.67 ± 31.73 g/m
2
, p<0.0001), smaller LV end diastolic diameter and left atrial size were noted (female vs. male, 46.47 ± 7.77 vs. 50.70 ± 8.57mm, p<0.0001; 41.39 ± 8.00 vs. 42.34 ± 7.99mm, p<0.0001). In addition, more usage of guideline-directed HF medications were noted in female pts (p<0.0001). After multivariate adjustment, significantly lower risk of longterm all cause death and CV death were noted in female pts compared to male (adjust hazard ratio [aHR]: 0.89, 95% confidence interval [CI]: 0.85-0.94; aHR: 0.90, 95% CI: 0.74-0.88, respectively) over 8-year followup by Kaplan-Meir curve analysis. However, risk of HF rehospitalization was similar between female and male pts (aHR: 1.02, 95% CI: 0.95-1.09).

Conclusions:
Significant differences in clinical characteristics, echocardiographic findings, long-term CV mortality and all-cause mortality were observed between female and male pts with HF in the present cohort.