bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9397: Sonothrombolysis Improves Cardiac Segmental Contractility, Myocardial Perfusion and Baroreflex Gain in Patients With ST-segment Elevation Myocardial Infarction (stemi) in Long-Term Follow-Up
Authors: Azevedo Luciene F , Borges Bruno Carter C , Toschi-Dias Edgar , Ferreira-santos Larissa , Groehs Raphaela V , Tsutsui Jeane M , Guimaraes Amisa , oliveira marco C , smanio Paola E , Porter Thomas R , Mathias Wilson
Published: April 2024

Sonothrombolysis (Sono) has improved microvascular obstruction, global contractility and infarct area after STEMI.

Objective:
To evaluate the long-term effect of Sono and its physiologic mechanisms in a subgroup of 51 STEMI patients (percutaneous coronary intervention-PCI (N=24) and PCI+Sono (N=27)) from previous randomized study. All patient were treated with PCI and those also treated with Sono received frequent image-guided diagnostic high mechanic index impulses applied to the myocardial contrast-enhanced areas (microbubbles) in the apical views (1.8 MHz; 1.1 to 1.3 MI; <5-μ pulse duration). Evaluations were at pre-treatment, 1 month (ultrasound-US with contrast agent) and at averaged 34±17 months after STEMI (US with contrast agent; cardiac and peripheral sympathetic activity by means of
123
I-MIBG cardiac scintigraphy and microneurography; baroreflex gain of heart rate (HR) control by means of transfer function analysis). (For significance: P level ≤ 0.05). US values are on table. Adding, PCI+Sono showed lower left ventricular end-diastolic volume (LVEDV) remodelling (22±36 vs. 44±42%, P<0.05). Cardiac scintigraphy showed similar late Heart/Mediastinum ratio and similar washout rate between groups. Muscle sympathetic nervous activity was also similar in both groups. PCI+Sono showed higher baroreflex gain of HR control (8±3 vs. 6±2 ms/mmHg, P=0.05), indicating an improved baroreflex sensitivity. In addition, perfusion score index correlated positively with wall motion score index (r=0.97, P<0.001) and washout rate (r=0.30, P=0.04). LV ejection fraction correlated negatively with wall motion score index (r=-0.53), perfusion score index (r=-0.48) and LVEDV (r=-0.29) (P<0.05). In conclusion, Sono added to PCI improved contractility and myocardial perfusion in STEMI. Despite high level of sympathetic activity, baroreflex gain of HR was ameliorated in PCI+Sono patients, probably due to better myocardial perfusion and lower LV remodelling.
Abstract 9398: Dantrolene Prevents Doxorubicin-Induced Cardiac Ryanodine Receptor Dyssynchrony
Authors: Aggarwal Arjun K , Azam Mohammed Ali , Chakraborty Praloy , Massé Stéphane , Niri Ahmed , Lai Patrick F , Riazi Sheila , Billia Filio , Dadson Keith , Nanthakumar Kumaraswamy
Published: April 2024

Background:
Ryanodine receptor 2 (RyR2) is important for cardiac calcium release from the sarcoplasmic reticulum. RyR2 activation triggers a spatio-temporally regulated calcium spark. Synchronous activation of RyR2 clusters creates a steeper slope and shorter systolic rise time in calcium transients. Doxorubicin (Dox) is a commonly used chemotherapy drug that can lead to dyssynchronous RyR2 activation and cardiomyopathy. We therefore sought to investigate the effects of RyR2 stabilizer dantrolene (Dan) on restoring normal RyR2 synchrony of calcium release in a murine model of doxorubicin-induced cardiomyopathy.

Hypothesis:
We hypothesize that treatment with dantrolene will mitigate RyR2 dyssynchrony induced by doxorubicin.

Methods:
22 adult male C57BL/6 mice were randomly divided into four groups: (i) Control, (ii) Dox only (single intraperitoneal injection, 10 mg/kg on day 7), (iii) Dan only (10 mg/kg daily starting on day 0 through day 21), and (iv) Dan + Dox. Two weeks after Dox treatment, the hearts were harvested and perfused in a Langendorff setup. Calcium-sensitive dye Rhod-2AM and mechanical uncoupler Blebbistatin were infused. Each heart was electrically stimulated following a pace-and-pause protocol during optical mapping of the anterior ventricular wall. Dye fluorescence was recorded and analyzed using custom MATLAB codes. Time to rise (TTR), the time duration for Rhod-2AM fluorescence to rise from minimum (10%) to maximum (90%) in each heartbeat, was used as a means of assessing RyR2 synchrony.

Results:
TTR was prolonged in the Dox group compared to control (11.6±1.3 ms in Dox group vs. 10.1±0.6 ms in control; at 14 Hz). Treatment with Dan prevented this prolongation (11.6±1.3 ms in Dox group vs. 9.8±0.6 ms in Dan+Dox group; at 14 Hz).

Conclusions:
Our findings suggest that dantrolene is effective in mitigating RyR2 dyssynchrony induced by doxorubicin.
Abstract 9803: Most SCN5A Missense Loss-of-Function Variants Also Have a Dominant Negative Effect
Authors: Oneill Matthew J , Muhammad Ayesha , Hall Lynn , Solus Joseph F , Short Laura , Roden Dan M , Glazer Andrew
Published: April 2024

Introduction:
Up to 30% of patients with Brugada Syndrome (BrS) carry loss of function (LoF) variants in the cardiac sodium channel gene
SCN5A
. Recent studies have suggested that the protein product Na
V
1.5 can form dimers, suggesting the possibility that LoF variants may have dominant negative effects.

Methods:
We identified 36
SCN5A
missense variants previously found to have peak current <10% compared to wild-type (WT). HEK293T cells were engineered to stably express one or two copies of
SCN5A
using AttB-AttP landing pad and Sleeping Beauty transposon systems. Cell lines were created expressing the missense LoF
SCN5A
variants alone or in heterozygous co-expression with WT
SCN5A
. Channel expression was validated by flow cytometry and peak sodium currents were measured using automated patch clamp (>20 replicate cells/variant). To assess clinical risk, we compared case versus control ratios among different variant mechanisms using a published BrS case consortium and the gnomAD population database.

Results:
32/36 LoF variants studied alone had peak current <10% as expected. In heterozygous experiments, WT alone was normalized to 100% and WT+WT showed ~200% peak current. In heterozygous expression with WT, 29/32 LoF variants showed a reduction to less than 75% normalized peak current, demonstrating a dominant negative effect. We next tested the hypothesis that dominant negative variants carry a higher disease risk than other variant classes. We observed a 5.0-fold enrichment for BrS cases among carriers of dominant negative missense variants compared to putative haploinsufficient variants (frameshift/splice site) (p=0.003).

Conclusions:
Most
SCN5A
missense LoF variants also have a dominant negative effect. Case-control comparisons reveal that this variant class carries an outsized BrS risk compared to other classes of pathogenic variants.
Figure
.
A)
SCN5A
homozygous expression.
B)
SCN5A
heterozygous expression.
C)
Case-control analysis.
Abstract 9809: Mortality, Hospitalization, and Cardiac Interventions in Atrial Fibrillation Patients Younger Than 65 Years
Authors: Bhonsale Aditya , Zhu Jianhui , Thoma Floyd W , Kancharla Krishna , Voigt Andrew , Magnani Jared W , Estes N A , Saba Samir , Mulukutla Suresh R , Jain Sandeep
Published: April 2024

Introduction:
The risk factor burden, and long-term outcome among atrial fibrillation (AF) patients under 65 years of age is unclear.

Methods:
The study population included 67,221 (mean age 72.4 ± 12.3, 45% female) adult patients with AF evaluated at the University of Pittsburgh Medical Center between 1/2010 and 12/2019. Hospital system wide electronic health records and administrative data using
International Classification of Disease 9 and 10 revisions
was utilized to ascertain risk factors, comorbidities, and subsequent mortality and hospitalization stratified according to age at initial evaluation. Association of AF with all-cause mortality among those < 65 years was analyzed using an internal contemporary cohort of patients without AF (n=918,073).

Results:
17,335 patients (26%) were less than 65 years of age (32% female, 92% white) with considerable cardiovascular risk factors (current smoker 16%, BMI 33.0 ± 8.3, hypertension 55%, Diabetes Mellitus 21%, congestive heart failure 20%, Coronary artery disease 19%, prior ischemic stroke 6%) and comorbidity burden (COPD 11%, Obstructive sleep apnea 18%, CKD 1.3 %). Over mean follow up of > 5 years, 2084 (6.7% <50 years; 13% 50-65 years) patients died. Proportion of patients with >1 hospitalization for MI, HF and Ischemic stroke was 1.25%, 4.8%, and 1.05% for those <50 years and 2.2%,7.4%, and 1.1% for the 50-65 years subgroup respectively. Multiple cardiac and non-cardiac risk factors were associated with increased mortality in younger AF patients with HF and hypertension demonstrating significant age-related interaction (p=0.007 and p=0.013 respectively). AF patients experienced significantly worse survival when compared to comorbidity adjusted patients without AF (Males <50y HR 1.49 (1.24-1.79), 50-65y HR 1.34 (1.26-1.43); Females <50y HR 2.4 (1.82-3.16), 50-65y HR 1.75 (1.6-1.92)).

Conclusions:
AF patient <65 years of age have significant comorbidity burden and considerable long-term mortality. They are also at a significant increased risk of hospitalization for HF, stroke, and myocardial infarction. Cardiac and non-cardiac comorbidities are independently associated with worse outcome in these patients and warrant aggressive risk factor and comorbidity evaluation and management.
Abstract 9811: Bone Marrow-Derived Mir-181a/b Controls Hematopoiesis, Monocytosis, and Angiogenic Responses in Diabetic Critical Limb Ischemia
Authors: Cheng Henry S , Zhuang Rulin , Perez-Cremades Daniel , Chen Jingshu , Jamaiyar Anurag , Henao-Mejia Jorge , Goodney Philip P , Sabatine Marc S , Creager Mark A , Bonaca Marc P , Feinberg Mark W
Published: April 2024

Introduction:
Humans with peripheral artery disease (PAD) that develop critical limb ischemia (CLI) have a high risk of amputation and cardiovascular complications. Diabetes mellitus (DM) is a prominent risk factor in development of CLI, yet the molecular mechanisms remain incompletely understood.

Objective:
To investigate microRNA biomarkers and their involvement in the pathogenesis of CLI in human subjects and mice with and without diabetes.

Methods:
miRNA-seq of diabetic patients with or without CLI was compared to diabetic mice with acute or subacute limb ischemia to identify conserved miRNAs. miRNA knockout (KO) mice on chow or high fat diet were generated to explore impact on CLI.

Results:
miR-181
family members were among the top conserved miRNAs from mice to human subjects. Compared to wild type (WT) controls, systemic
Mir181a2b2
KO mice on chow-fed diet had increased blood flow recovery following FAL and higher M1-macrophage polarization in ischemic skeletal muscles. KO macrophages increased CCL4 and VEGFA to promote angiogenesis. Conversely, diabetic KO mice had impaired revascularization in limbs compared to WT, due to abrogation of circulating Ly6C
hi
monocytes with reduced accumulation of macrophages in ischemic skeletal muscles. Furthermore, M2-like macrophages deficient of
miR-181a/b
under diabetic conditions failed to produce pro-angiogenic cytokines. Reduced monocytosis in KO mice was a result of impaired hematopoiesis with increased CXCR4 signaling in Lin
-
Sca1
+
Kit
+
(LSK) cells in the bone marrow. Importantly, supplying diabetic KO mice with exogenous delivery of Ly6C
hi
monocytes from non-diabetic KO mice rescued the impaired revascularization after limb ischemia.

Conclusions:
MiR-181a/b
is a putative biomarker of diabetic CLI and contributes to alterations in hematopoiesis, monocytosis, and macrophage polarization. Pathways regulated by
miR-181a/b
may provide therapeutic targets for PAD patients at risk of developing CLI.
Abstract 9833: Incidence and Predictors of Acute Limb Ischemia in Patients with Acute Myocardial Infarction Complicated by Cardiogenic Shock - Insight from National Readmission Database
Authors: Romero Carlos Manuel , Shafi Irfan , Patil Aadhar , Singh Maninder , Lakhter Vladimir , Bashir Riyaz
Published: April 2024

Introduction:
Cardiogenic shock (CS) is an ominous complication of acute myocardial infarction (AMI) that has a mortality as high as 50%. Use of percutaneous mechanical circulatory support devices (MCSD) has increased in attempts to improve outcomes, however its use can be complicated by acute limb ischemia (ALI). In contemporary clinical practice the incidence and predictors of this complication not known.

Methods:
Patients with index hospitalizations for AMI complicated by CS in the U.S. Nationwide Readmissions Database were identified from January 2016 to December 2018 using International Classification of Diseases (ICD) 10 codes (“I21-”, “I214”, “R57-”). We evaluated the incidence of ALI and its impact on mortality, length of stay, and cost of hospitalization. We used logistic regression analysis to determine independent predictors of ALI in this population.

Results:
Amongst a total of 61,950 patients had AMI complicated by CS and 922 (1.49%) developed ALI. The rates of ALI increased from 1.29% in 2016 to 1.66% in 2018. Utilization of microaxial MCSD increase from 2.245% in 2016 to 14.03% in 2018. The major predictors of ALI included peripheral arterial disease (PAD) (OR, 7.86, 95% CI 6.34 to 9.76), veno-arterial extracorporeal membrane oxygenation (ECMO-VA) cannulation (OR, 2.96, 95% CI of 1.53 to 5.73), and microaxial MCSD implantation (OR, 2.91, 95% CI of 2.48 to 3.41). (Figure 1). ALI patients had higher mortality (41.37% vs 34.07%, p=<0.001), longer length of stay (17.33 ± 17.92 vs 9.73 ± 11.43) and higher charges (507,955 ± 610,337 vs 249,904 ± 305,385).

Conclusions:
This nationwide observational study shows that ALI is not an infrequent complication in patients with AMI complicated by CS. This complication is associated with higher mortality, and longer length of stay. Presence of PAD and use of MCSD is associated with significantly higher risk of ALI.
Abstract 9843: Sex-Related Differences in Premature Cardiovascular Disease in Individuals with Familial Hypercholesterolemia
Authors: Agarwala Anandita P , Deych Elena , Jones Laney , Sturm Amy C , Aspry Karen E , Ahmad Zahid , Ballantyne Christie M , Goldberg Anne C
Published: April 2024

Background:
Familial hypercholesterolemia (FH) is associated with elevated risk for premature atherosclerotic cardiovascular disease (ASCVD) (<55 years in men and <65 years in women). Little is known about sex-specific differences in risk factors and treatment outcomes in individuals with FH and premature ASCVD.

Objective:
To characterize sex-specific risk factor burdens and treatment outcomes in individuals with FH and premature ASCVD.

Methods:
The prevalence of premature ASCVD in 782 adults with FH (diagnosed by clinical scores and/or genetic testing) from 7 US-based lipid clinic practices was assessed retrospectively. A multivariate logistic mixed effects model with random study site effect and sex-specific analysis was used to determine the strongest predictors of premature ASCVD, and lipid treatment outcomes. Covariates included age, sex, diabetes mellitus (DM), hypertension (HTN), and current smoking.

Results:
98/280 men and 89/502 women had premature ASCVD. Women with premature ASCVD were older by an average of 3 years (mean age 58 vs. 55 years, p= 0.04) and had higher on treatment total cholesterol (216 vs. 178 mg/dl, p<0.001) and LDL-C (135 vs. 109 mg/dl, p= 0.005) (Table 1). In men, the strongest predictors of premature ASCVD were HTN (OR 5.39, 95% CI 2.85, 10.93, p<0.001) and DM (OR 2.25 95% CI 1.17, 4.37, p=0.016). In women, the strongest predictors of premature ASCVD were HTN (OR 5.48, 95% CI 3.22, 9.71, p<0.001) and smoking (OR 2.85, 95% CI 1.35, 5.94, p=0.005). Treated LDL-C was not a significant predictor of ASCVD in either men or women.

Conclusion:
The normal delay in age of onset of ASCVD in women vs. men may be shortened in individuals with FH. Both women and men with FH have an increased risk of premature ASCVD in the setting of HTN, but risks from smoking and DM differ by sex. Women with FH and premature ASCVD had higher on-treatment LDL-C. Aggressive treatment strategies are needed to reduce risk factor burdens and residual hyperlipidemia in these patients.
Abstract 9845: Novel Oral Anticoagulants versus Vitamin K Antagonists in Patients with Atrial Fibrillation After Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis
Authors: Memon Muhammad , Siddiqui Asad Ali , Amin Emaan , Shaikh Fahd Niaz , Khan Mohammad , Doukky Rami , Krasuski Richard
Published: April 2024

Background:
The efficacy and safety of novel oral anticoagulants (NOACs) compared to the current guideline-recommended vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients undergoing transcatheter aortic valve replacement (TAVR) has not been well established. We pooled evidence from all available studies to assess the risks and benefits of this drug class.

Methods:
We queried electronic databases (MEDLINE, Scopus, and Cochrane central) up until 15
th
May 2021 for studies comparing NOACs to VKAs in AF patients undergoing TAVR. Results from studies were presented as risk ratios (RR) with 95% confidence intervals (CI) and pooled using a random-effects model. Subgroup analysis by study design and meta-regression analysis were performed to explore heterogeneity.

Results:
A total of 12 studies (4 RCTs and 8 retrospective observational) containing 13,815 patients (mean age 81.1 years; 50.1% men) were identified and included in the analysis. Pooled analysis revealed no significant difference between NOACs and VKAs in terms of stroke or systemic embolism (RR 0.83; p=0.34), major bleeding (RR 0.84; p=0.30), intracranial hemorrhage (RR 0.72; p=0.60), all-cause mortality (RR 0.71; p=0.15), and myocardial infarction (RR 1.34; p=0.32) at a mean length of follow-up of 15.1 months. RCTs and observational studies did not significantly differ across outcomes on subgroup analysis. Meta-regression analysis found heterogeneity in all-cause mortality to be significantly explained by percentage of males (coefficient: 0.049, p=0.007), mean age (coefficient: 0.221, p<0.001), and CHA2DS2-VASc score (coefficient: -1.657, p<0.001).

Conclusions:
This meta-analysis suggests that outcomes with NOACs do not significantly differ compared to VKAs following TAVR in patients with AF. Future RCTs may help provide a clearer answer.
Abstract 9870: Covid-19 is Associated with Increased In-Hospital Mortality in Patients Hospitalized for Acute Myocardial Infarction: A Meta-Analysis of Observational Studies
Authors: Baral Nischit , Poudel Sangeeta , Itani Asmita , Adhikari Yadav Saroj A , Gautam Swotantra , Gismalla Mohamed , Abdelazeem Basel , Isa Sakiru , Christy Joshua , Rafae Abdul , Ranabhat Bandana , Savarapu Pramod , Kunadi Arvind , Gupta Tripti , Pokharel Yashashwi
Published: April 2024

Introduction:
Corona Virus Disease 2019 (COVID-19) Infection is associated with acute cardiac injury. We examined the risk of in-hospital mortality in patients with concomitant COVID-19 infection and acute myocardial infarction (AMI) as compared to patients with AMI without COVID-19 infection.

Hypothesis:
COVID-19 is associated with increased in-hospital mortality in patients hospitalized for AMI.

Methods:
We conducted a systematic review and meta-analysis of published articles from January 2019 to May 2021. Literature search was performed on PubMed, Cochrane database, Embase, and Web of Science. We included studies done in patients with index hospitalization for AMI. Patients with positive COVID-19 Polymerase Chain Reaction were considered to have COVID-19 infection. We used random-effects model using the risk ratio (RR) and 95% confidence interval (CI). We used I squared test to assess for heterogeneity.

Results:
After assessing 20 articles for full text screen for eligibility, four cohort studies met our inclusion criteria. There were a total of 1918 participants in both COVID and non-COVID groups, who were hospitalized for AMI between February 1, 2020 to June 30, 2020. 168 participants (8.76%) had concomitant COVID-19. Confounders were adjusted in only one article. Most of the confounders like age, sex, race and BMI were similar in both groups but co-morbidities were higher in COVID group in all four studies. 42 patients (61%) with COVID-19 and 69 patients (0.96%) with no COVID-19 died in hospital. Pooled data from the four studies showed patients with AMI and COVID-19 infection had more than six times increased risk of in-hospital mortality compared with patients who had AMI but no COVID-19 infection (RR 6.17, 95% CI: 4.11-9.26; I
2
=9%, P<0.00001).

Conclusions:
Our study shows that COVID-19 infection is associated with increased in-hospital mortality in patients hospitalized for AMI. Our limitations include higher comorbidities in COVID group, unable to capture all COVID patients, and high risk of bias with cohort studies. Whether patients with concomitant COVID-19 infection and AMI will benefit from unique management approaches should be further examined.
Abstract 9874: Cardiovascular Safety of Sleeve Gastrectomy vs. Roux-en-y Gastric Bypass Among Older Patients with Type 2 Diabetes
Authors: Suissa Karine , Schneeweiss Sebastian , Hutter Matthew , Kim Seoyoung C , Patorno Elisabetta
Published: April 2024

Introduction:
Surgical treatment for obesity, a major risk factor for diabetes and cardiovascular disease, may lead to important improvements in cardiovascular health. Sleeve gastrectomy (SG) procedures have gained popularity over Roux-en-Y gastric bypass (RYGB), though it is unclear which procedure results in improved cardiovascular outcomes. Our objective was to evaluate the comparative cardiovascular safety of SG vs. RYGB in older patients with type 2 diabetes (T2D).

Methods:
Using Medicare claims data, we identified a cohort of T2D patients ≥65 years that underwent a SG or RYGB procedure between 2010 and 2018. Patients undergoing a SG were propensity-score (PS) matched 1:1 to RYGB patients on the propensity score of receiving the procedure. The two co-primary outcomes were a major adverse cardiovascular event (MACE, a composite of stroke, myocardial infarction (MI) or all-cause mortality) and hospitalization for heart failure (HHF). Secondary outcomes were the individual components of MACE. Subjects were followed until the occurrence of an outcome, end of patient data or enrollment or death, whichever came first. We estimated the hazard ratios (HR) for each outcome, adjusting for demographics, comorbidities, medication use and healthcare utilization using PS matching.

Results:
A total of 5,514 patients undergoing SG were PS-matched to 5,514 undergoing RYGB and followed for a median of 2.3 years (IQR: 1.2, 3.9) after the procedures. Compared to RYGB, patients undergoing SG had a similar risk of MACE (rate 2.5 vs. 3.0 per 100 person-years (py); HR: 0.94; 95% CI: 0.82, 1.09) and of HHF (rate 12.2 vs. 10.9 per 100 py; HR: 1.01; 95%CI: 0.94, 1.09). For secondary outcomes, the risk of MI was higher for SG (rate 0.8 vs. 0.7 per 100 py; HR: 1.33, 95%CI: 1.02, 1.75), whereas SG was associated with a lower risk of all-cause mortality (rate 1.5 vs. 2.2 per 100 py; HR: 0.68; 95%CI: 0.57, 0.81).

Conclusions:
In older patients with T2D, SG was associated with a similar risk of MACE and HHF compared to RYBG. However, when we assessed the individual components of MACE separately, SG was associated with a higher risk of MI and a lower risk of death, compared with RYBG.
Abstract 9875: Pain is More Severe in Women Than Men with Heart Failure Transported by Emergency Medical Services
Authors: Smith Asa B , Jung Miyeon , Pressler Susan J
Published: April 2024

Introduction:
Presence and severity of pain may differ between women and men with heart failure (HF) transported by emergency medical services (EMS), but few studies have examined these differences. The aims were to compare (1) presence of pain, (2) pain severity, and (3) demographic and clinical factors associated with pain presence and severity between women and men with HF.

Methods:
Data were analyzed from electronic medical records of 6,582 patients with HF transported by EMS. Presence of pain was operationalized by having a primary complaint of pain during transport. Pain severity was recorded among patients with a primary complaint of pain (n=400) on a 0-10 scale, with 10 indicating worst pain. Demographic (gender, age, race) and clinical variables (vital signs, conditions, medications, devices) were retrieved from the medical record. Descriptive statistics and multiple linear and logistic regression were used to address the aims.

Results:
The sample was 57.6% women and 42.4% men. The mean age was 64.2 (SD 14.5). Self-reported race was 58.2% Black and 41.8% White. Pain was frequent, with 23% of women and 23% of men presenting with a primary complaint of pain. Pain severity was ‘moderately high’ to ‘high’, with a mean of 7.2 (SD 2.9) among women and 6.4 (SD 3.2) among men (p=0.005). In logistic regression models, significant explanatory factors for pain presence in women were younger age (OR=0.97; p<0.001), MI history (OR=1.85; p<0.001), and absence of shortness of breath (OR=0.72; p<0.001). In men they were younger age (OR=0.97; p<0.001), MI history (OR=2.05; p<0.001), and presence of an implantable cardioverter-defibrillator (OR=1.64; p=0.022). In multiple regression models, higher pain severity in women was explained by younger age (β=-0.04; p=0.012) and higher systolic BP (β=0.02; p=0.001) The adjusted R
2
was 0.09. In men, higher pain severity was explained by younger age (β=-0.08; p=0.003) and Black race (β=-1.65; p=0.007). The adjusted R
2
was 0.05.

Conclusions:
Presence of pain was similar between women and men with HF, but women had more severe pain. Pain severity was explained by different factors in women and men. Prospective studies of pain with gender-focused analyses and additional explanatory factors to account for more variance are needed.
Abstract 9884: Supranormal Left Ventricular Ejection Fraction and Risk of Major Adverse Cardiovascular Events: Findings from the Multi-Ethnic Study of Atherosclerosis and Dallas Heart Study
Authors: Shah Sonia , Kondamudi Nitin , Segar Matthew W , Ayers Colby , Matulevicius Susan A , Chandra Alvin , Abbara, MD Suhny , Michos Erin , Lima Joao , Peshok Ron , Drazner Mark H , Pandey Ambarish
Published: April 2024

Introduction:
Left ventricular (LV) systolic dysfunction is associated with a higher risk of adverse cardiovascular (CV) outcomes. However, the prognostic implication of supranormal LV ejection fraction (LVEF), as assessed by cardiac MRI, among adults with no prior CV disease (CVD) is unknown.

Methods:
Participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and Dallas Heart Study (DHS) who were free of CVD at baseline and underwent cardiac MRI with LVEF above the normal MRI cutoff (≥57%) were included. The association between cohort specific LVEF categories and risk of clinically adjudicated major adverse CV events (MACE) was assessed using adjusted Cox models. The association between continuous measures of LVEF and risk of MACE was assessed in a pooled cohort analysis using cohort-specific Z-scores of LVEF.

Results:
There were 4,703 participants from MESA (mean age 62, 25% black, 54% women, median follow up 13.1 years) and 2,287 participants from DHS (mean age 44, 46% black, 57% women, median follow up 12 years) with 747 and 151 MACE events, respectively. In both cohorts, participants across increasing LVEF quartiles (MESA Q1 mean LVEF=63% vs. Q4 mean LVEF=78%) were older and had a higher burden of CV risk factors. Among cardiac parameters, across increasing quartiles, LV end-diastolic volume (Q1: 69.9 vs. Q4: 64.6 ml/m2) and LV mass (Q1: 79.1 vs. Q4: 74.9 gm/m2) significantly decreased (p<0.001), while LV stroke volume (Q1: 43.8 vs. Q4: 49.8 ml/m2) increased (p<0.001). In adjusted Cox models, the risk of MACE was highest among individuals in LVEF Q4 (vs. Q1) in both cohorts (Figure A). Similar patterns of association were observed between continuous distribution of LVEF and risk of MACE in the pooled analysis (Figure B).

Conclusions:
Among community-dwelling adults without CVD, supranormal LVEF is associated with elevated risk of MACE. Future studies are needed to elucidate the mechanisms underlying risk of CVD among individuals with supranormal LVEF.
Abstract 9891: Are CAC Scores Less Valuable for Patients of Low Socioeconomic Status?
A Dallas Heart Study Analysis
Authors: Berlacher Mark , Triana Taylor , Wu Elaine C , Rao Shreya , Powell-wiley Tiffany , Pandey Ambarish , Joshi Parag H , Khera Amit
Published: April 2024

Background:
Low socioeconomic status (SES) is associated with atherosclerotic cardiovascular disease (ASCVD) and possible underestimation of risk by the pooled cohort equations (PCE). Whether coronary artery calcium (CAC) scores can improve risk discrimination in those with low SES is unknown.

Methods:
Individuals from the Dallas Heart Study free of ASCVD and with CAC scanning were evaluated. Low SES was defined as an annual income <$16,000 or an educational attainment level ≤11 years. Unadjusted and adjusted analyses assessing the relationships between SES and 1) CAC scores and 2) ASCVD events (fatal or non-fatal MI or stroke) were performed. The incremental predictive value of CAC in those at low and higher SES was assessed using c-statistics (PCE alone vs PCE + CAC).

Results:
Among 2246 individuals (mean age 44 yrs, 55% women, 45% Black), 115 ASCVD events occurred over a median of 12.5 years. Low SES by income (n=451) was associated with increased risk of ASCVD after adjustment for risk factors (HR 2.16, 95% CI 1.37-3.42), but was not independently associated with CAC. Higher CAC scores (0, 1-99, ≥100) tracked with increased 10-year ASCVD event rates in those at low (5, 10, and 22%) and higher SES (0.002, 4, and 11%), with low SES groups carrying greater ASCVD risk for every stratum of CAC, including with CAC=0. In multivariable models compared with CAC=0, those with CAC 1-99 and ≥100 had a greater risk of ASCVD events for individuals at higher SES [HR 3.40 (1.5-7.8), and 4.8 (1.9-12.6)], but not for those with low SES [HR 1.00 (0.4-2.4), and 1.6 (0.6-4.6)], (p-interaction CAC x SES=0.002). Similar results were found for low SES defined by education. The addition of CAC to PCE improved risk discrimination for individuals at higher SES, but not for individuals at low SES (Table 1).

Conclusion:
Individuals at low SES have significantly increased risk of ASCVD, however, CAC scores are not independently associated with ASCVD in this population and may be less useful in risk discrimination.
Abstract 9905: A Deep Neural Network Detects Elevated Right Ventricular Systolic Pressure Using Data Captured from a Digital Stethoscope
Authors: Guo Ling , Tiwari Urvi , Lastowski Emileigh , Chorba John S , Ilyas Suleman , Currie Caroline , Choudhary Gaurav , Maidens John , Saltman Adam
Published: April 2024

Introduction:
Pulmonary hypertension (PH) and elevated peak right ventricular systolic pressure (RVSP) are associated with poor outcomes in a number of cardiopulmonary diseases. PH often goes undiagnosed because right heart catheterization is invasive and expensive. RVSP measured by echocardiography has been used with some success as a non-invasive proxy, yet it is still expensive and operator-dependent, resulting in inadequate and/or delayed diagnosis of PH. We developed and evaluated an artificial intelligence (AI) tool to detect elevated RVSP, using phonocardiogram (PCG) recorded from digital stethoscopes.

Methods:
6,062 15-second PCG recordings were taken using the Eko CORE and DUO digital stethoscopes from 797 patients with corresponding echocardiogram-measured RVSP. These, plus an additional 169,160 unlabelled PCG recordings with no corresponding echocardiogram, were used to train a deep convolutional neural network to identify an RVSP above 40mmHg. Mel spectrograms from the PCGs were randomly cropped into 5s segments and used to train the network. The networks were evaluated via 5-fold cross validation with the folds split by patient to prevent leakage between training and test sets.

Results:
Across the 5 cross validation folds, the model produced an average area under the ROC curve of 0.79 (range 0.76 - 0.85), sensitivity of 0.73 (range 0.67 - 0.80) and specificity of 0.74 (range 0.64 - 0.82) at detecting a peak RVSP >= 40 mmHg. Incorporating patient age, gender and body mass index into the network did not improve performance.

Conclusions:
We demonstrated the ability of an AI tool to detect elevated peak RVSP using PCG. Use of a digital stethoscope with this tool has the potential to be a low-cost, rapid and minimally invasive screen for elevated RVSP in a point-of-care setting, to increase early detection of PH.
Abstract 9910: Effect of Renal Denervation in Resistant Hypertension: A Meta-Analysis of Randomized Controlled Trials
Authors: Selvaraj Vijairam , Ansari Affan , Mishra Ajay K
Published: April 2024

Introduction:
Resistant hypertension is defined as blood pressure that remains ≥ 140/90 mm Hg despite adherence to at least three maximally tolerated doses of antihypertensive medications, including a diuretic. Catheter based renal denervation has been studied as one of the interventions for blood pressure control in such patients. Data comparing renal denervation versus sham procedure have shown disparate results. This meta-analysis summarizes the current evidence on the effect of sham controlled renal denervation on the treatment of resistant hypertension.

Methods:
Embase, Pubmed and Cochrane Central databases were searched from inception until May 30, 2021. RCTs comparing catheter based renal denervation with a sham control were included. Outcomes assessed were change in 24h ambulatory systolic blood pressure, change in 24h ambulatory diastolic blood pressure, change in office systolic blood pressure, and change in office diastolic blood pressure. Weighted mean differences (WMD) were calculated and pooled into a random effects model meta-analysis.

Results:
Seven studies with 1,264 participants were included in the analysis. Catheter based renal denervation was associated with significant decrease in ambulatory systolic blood pressure (WMD: -3.76; 95% CI: -2.44 to -5.09, p value <.00001) and ambulatory diastolic blood pressure (WMD: -1.78; 95% CI: -0.84 to -2.72, p value=0.0002) compared with sham. The reduction in office systolic and office diastolic blood pressure was also significantly greater with catheter renal denervation than sham control (WMD: -5.95; 95% CI: -3.93 to -7.97; p value<0.00001 and WMD: -3.54; 95% CI: -2.35 to -4.72; p value<0.00001).

Conclusions:
There was significant benefit of renal denervation for resistant hypertension for all the studied outcomes. Based on this data, compliant patients with resistant hypertension who are maxed on lifestyle and pharmacological management may benefit from catheter based renal denervation.
Abstract 9915: Impact of Arteriovenous Fistula and Non-Physiological Flow States in the Evaluation of Aortic Stenosis Among End-Stage Kidney Disease Patients on Dialysis
Authors: Ogugua Fredrick , Ternacle Julien , Rodin Holly , Pibarot Philippe , Shroff Gautam R
Published: April 2024

Introduction:
Aortic stenosis (AS) progresses rapidly and unpredictably in ESKD and is an independent risk factor for mortality. Making an accurate diagnosis and assessing severity of AS on TTE is critical to inform management decisions. TTE parameters of AS severity could be adversely impacted by presence of an arteriovenous fistula (AVF) and resultant non-physiological flow states in ESKD.

We aim to evaluate prevalence of non-physiological flow states in patients with ESKD and AS with AVF vs. other dialysis access types. We hypothesized that TTE parameters vital to accurate determination of severity of AS will defer in ESKD patients with AVF compared to other types of dialysis access.

Methods:
In this retrospective observational study, we identified unique ESKD patients on dialysis and concomitant AS from a single center between 1/1/2000 to 1/1/2021. Severity of AS was defined per 2014 AHA/ACC guidelines. We analyzed the TTE parameters of AS severity according to dialysis access modality. Aortic valve area (AVA) was determined by the continuity equation.

Results:
We included 94 patients; mean age 66 yrs, 71% male; 43% black, 40% white. Severe AS was present in 18%, moderate in 41% and mild in 41%. Fifty-three percent of patients had AVF, 17% arteriovenous graft, 15% peritoneal dialysis catheter, and 15% central venous access catheter. TTE parameters of flow state and AS severity did not demonstrate any significant differences across different dialysis access modalities. (Table 1) The results were similar after adjusting for AS severity grades.

Conclusions:
Among ESKD patients with AS, flow states and TTE parameters of AS severity were not different in the presence of an AVF compared to other dialysis access modalities. This study provides reassurance that conventional TTE parameters, including peak velocity, mean gradient, and AVA used to estimate AS severity can be utilized reliably in dialysis patients with AVF since non-physiological flow states were not prevalent.
Abstract 9931: Baseline Characteristics of Patients with Peripartum Cardiomyopathy; Mortality versus Left Ventricular Ejection Fraction Recovery Groups
Authors: Farhan Hasan Ali , Yaseen Israa Fadhil
Published: April 2024

Introduction:
Data about long term outcomes among patients with peripartum cardiomyopathy (PPCM) is limited. According to the 2018 ESC guideline for the management of cardiovascular disease during pregnancy, three factors are associated with adverse outcomes including baseline LVEF < 30%, LVEDD ≥ 60 mm, and right ventricular involvement.

Purpose:
To identify the baseline characteristics between two groups of patients with PPCM; patients with LVEF recovery within first year after diagnosis and patients who died within the same period after diagnosis. Also to identify the specific outcomes of the two groups.

Methods:
Retrospectively data were analyzed including patients with PPCM who had LVEF recovery within first year of diagnosis versus patients who died within one year after diagnosis. Data collected at cardio-obstetric clinic between January 2015 - November 2020.

Results:
Total number of patients who died within the first years were six patients while the total number of patients who had LVEF recovery within 1 year was 14 patients. Their clinical characteristics and outcomes are shown in table 1.

Conclusions:
Mortality group had less hypertension co-morbid disease, lower baseline systolic blood pressure, higher heart rate, lower LVEF, more right ventricular dysfunction, and less to be diagnosed in the postpartum period compared with LVEF recovered group. Use of spironolactone and bromocriptine were limited among both groups and light should be focus on this gap to be bridged. Lower rate of ACE-inhibitor use among mortality group may be explained by lower systolic blood pressure in this cohort. Most of the patients had LVEF recovery within the first 6-month and most of the patients in the other group died within the same period with sudden cardiac death as the leading cause of mortality.
Abstract 9940: Role Of Cardiology Clinical Pharmacist In The Management Of Peripartum Cardiomyopathy; Vulnerable Condition With Critical Interventions
Authors: Yaseen Israa Fadhil , Farhan Hasan Ali
Published: April 2024

Introduction:
Peripartum cardiomyopathy (PPCM) is a rare disease, however, mortality rate is reaching 24% as reported in the 2018 ESC guidelines for the management of cardiovascular disease during pregnancy. Awareness about optimal management and avoiding drug therapy complications is one of the essential keys to improve the outcomes of PPCM patients and could be achieved by expert multidisciplinary team work.

Methods:
To identify the role of cardiology clinical pharmacist among heart team in the management of PPCM patients, data about cardiology clinical pharmacist’s interventions in the management of 66 patients with PPCM was retrospectively collected and categorized into 6 categories. Study conducted at the cardio-maternal clinic where all the enrolled patients were prospectively diagnosed and followed up during and after pregnancy between 2015 - 2021 by heart team. Patients' follow-up was done either by clinic visit or by using telemedicine. All the pharmacist's interventions were agreed by the senior consultant cardiologist.

Results:
The cardiology clinical pharmacist performed 37 interventions and categorized into six categories as shown in figure 1. It was found that 8% of interventions were to stop duplication or triplication of the drug doses, as some patients were using two or three brands from the same drug believing that they are different therapies. Also 8% of interventions were correcting the use of wrong dose or drug, a problem which was happened due to an error by dispensing the dose or the drug to the patients from the private pharmacies.

Conclusions:
Cardiology clinical pharmacist has a vital role among heart team in the management of PPCM patients to reduce the serious drug therapy errors; which could be harmful for both mother and fetus, optimization of drug therapy, and reduce drug related complications.
Abstract 9946: Dapagliflozin versus Empagliflozin for Improving Outcomes of Type 2 Diabetes Mellitus Patients with Heart Failure and Reduced Ejection Fraction
Authors: Azuri Joseph , Aboalhasan Enis , Hammerman Ariel , Arbel Ronen
Published: April 2024

Introduction:
The co-morbidity of chronic heart failure and Type 2 diabetes mellitus (DM) is associated with a very high risk for CVmortality and HF-related hospitalizations (HHF). The Sodium-Glucose Transport protein 2 inhibitors (SGLT2i) dapagliflozin and empagliflozin improve the outcomes of this patient population. We aimed to compare their value for money for this indication.

Hypothesis:
Empagliflozin and dapagliflozin have comparable value for money for improving the HF outcomes of patients with HFrEF and DM.

Methods:
SGLT2i data was extracted from published results of empagliflozin and dapagliflozin in the subgroups of patients with co-morbidity of DM. The clinical outcome measure was HHF or CV mortality events. The economic measure was the cost needed to treat (CNT) to prevent one event, calculated by multiplying the one-year number needed to treat (NNT) to prevent one event by the annual cost of each therapy. Drug costs were based on the 2021 US National Average Drug Acquisition Cost prices. Secondary outcomes were the CNT to prevent one event of HHF and CV mortality as separate clinical outcomes. Sensitivity analysis was performed to mitigate differences between the trial’s populations

Results:
Treatment with empagliflozin in EMPEROR-REDUCED has resulted in an NNT of 17 (95% CI: 12-36) compared to 24 (95% CI: 16-60) with dapagliflozin in DAPA-HF. Accordingly the cost needed to treat to prevent one event of CVM or HHF was $81,550 (95% CI: $57,565-$172,694) and $108,563 (95% CI: $72,376-$271,408), respectively. The sensitivity analysis confirmed the primary results. The CNT to prevent CV mortality events is significantly lower with dapagliflozin and prevent HHF significantly lower with empagliflozin (Fig. 1).

Conclusions:
Empagliflozin and dapagliflozin have comparable value for money for improving HF outcomes of patients with HFrEF, with an advantage for dapagliflozin in CV mortality and for empagliflozin in preventing HHF.
Abstract 9954: Determinants of Death in Patients with Infective Endocarditis: A Population Attributable Risk Analysis
Authors: Li Hang Long , Tse Yi Kei Stephanie , Yu Si-Yeung , Ren Qingwen , Wu Meizhen , LI Kwan Yu , Wong Pui Fai , Hon Nicole Wing Lam , Lam Lok Yee Jane , Yu Shuk Yin , Yiu Kai Hang
Published: April 2024

Introduction:
Despite improvements in guidelines, the prognosis of infective endocarditis (IE) remains poor. To guide future development of management strategies, we aim to fill the knowledge gap and identify the evolving factors contributing to mortality.

Methods:
All patients diagnosed with IE from 2002 to 2019 were included from a well-validated territory-wide database in Hong Kong. Information including demographics, comorbidities and Charlson Comorbidity Index (CCI), microbiological culture and sensitivity tests, and surgical interventions were retrieved. The primary outcome was 1-year all-cause mortality. Using population attributable fraction (PAF) analysis, we quantified the relative contribution of each factor to the risk of death. The temporal trends in risk attributable to each factor was also evaluated using linear regression.

Results:
Of a total of 5139 patients (mean age 60 years, 37% female), 1642 (32%) died in one year. Age ≥ 60 years and CCI ≥ 1 were the most detrimental contributors to death, with PAF of 19.2% (14.5 to 23.9) and 14.6% (10.6 to 18.5), respectively (Figure). Concurrently, a hospital-acquired nature and severe renal disease also increased the risk of death, with PAF of 1.8% (0.2 to 3.4) and 1.8% (0.5 to 3.2), respectively. Methicillin-resistant Staphylococcus Aureus (MRSA) endocarditis was the most important microbiological factor penalizing survival (PAF 3.4% [2.5 to 4.3]). Surgical intervention was protective, with PAF of -7.9% (-9.5 to -6.4), and the PAF of surgery significantly increased over time (P < 0.001).

Discussion:
Age, comorbidities, impaired renal function, hospital-acquired IE and MRSA were the most detrimental contributors to adverse outcomes; the mounting coexistence represents a major challenge to diagnosis, treatment, and prognosis. Surgical intervention offered significant and increasing survival benefits, and a surgery-centered approach in management of endocarditis should be promoted.
Abstract 9957: Totum-070 Prevents Diet-Induced Hypercholesterolemia in Western Diet Fed Mice
Authors: Langhi Cedric , Otero Yolanda F , Le Joubioux Florian , Guigas Bruno , PELTIER Sébastien , Sirvent Pascal
Published: April 2024

It is well known that hypercholesterolemia is an important modifiable risk factor in the development of cardiovascular disease. Lowering blood cholesterol level reduces the incidence of atherosclerotic disease. TOTUM-070 (T070) is a clinical stage polyphenol-rich active substance composed by the association of 5 plant extracts. We assessed the hypothesis that administration of T070 prevents hypercholesterolemia in western diet fed mice and explored the potential mechanisms involved. C57BL/6 mice were fed either a normal diet (ND) or western diet (WD) for 6 weeks and received either vehicle or T070 (1mg/kg or 3mg/kg) daily by gavage (n=14 mice per group). Supplementation with T070 had no effect on food intake along the study duration. At the end of the study, body weight in WD-fed mice was increased to 28.3 ± 0.8 g compared to the ND group (24.5 ± 0.4 g, p<0.001). Interestingly, a significant (p<0.01) 29% reduction in body weight gain was observed in the T070 3mg/kg group compared to the WD group at the end of the study. Compared to WD group (298 ± 8 mg/dl), total-cholesterol in mice supplemented by T070 was reduced in a dose dependent manner (276 ± 9 mg/dl T070 1mg/kg, (p=0.19) and 265 ± 8 mg/dl T070 3mg/kg, p<0.05). There was no change in triglyceridemia among the groups compared to the ND mice. However, hepatic steatosis induced by the WD was reduced by 73% (p<0.001) in the T070 3mg/kg group. Hepatic and intestinal gene expression were drastically altered by WD feeding compared to ND, while supplementation with T070 tended to restore normal level of expression of many genes implicated in lipid and lipoprotein metabolism. A significant increase in feces production was observed in mice supplemented with T070 3 mg/g compared to the mice fed with WD alone (234 ± 7 mg/day WD+T070 3mg/g
vs
207 ± 6 mg/day WD, p<0.01), probably contributing to the beneficial phenotype induced by T070 administration. In conclusion, our results demonstrate the beneficial effect of supplementation with TOTUM-070 to prevent induction of hypercholesterolemia in a nutritional mouse model. This study highlights the interest of using TOTUM-070 for management of mild hypercholesterolemia.