bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12170: The Impact of Frailty on Urea Metabolism in Tanushimaru Cohort Study
Authors: Morikawa Nagisa , Enomoto Mika , Fukami Ako , Sato Hiromi , Yoshimura Harumi , Adachi Hisashi , Fukumoto Yoshihiro , Takahashi Kazuo , Kitada Kento , Yano Yuichiro , Nishiyama Akira
Published: December 2023

Introduction:
Urea metabolism activation, that is urea production, is thought to be very important as a body response for water retention in the process of human evolution. However, it is not clear how that body response is changing as aging. Previous metabolomics studies suggested that various metabolites were influenced by frailty. Thus, we investigated the association between frailty and urea metabolism (urea cycle and TCA cycle) in this study.

Methods:
We recruited 976 participants who had a health check-up in 2009 and were followed in 2018 in the prospective Tanushimaru cohort study. We defined people with cognitive decline ((≧28 score of Mini-Mental State Examination (MMSE) in 2009 and 24-27 score in 2018), slow gait speed (<1m/s), weaker grip strength (<28kg in men or <18kg in women) in 2018 and weight loss (difference in weight ≧ 4.5kg or 5% of weight in 2009) as “frail-like group”, while those with normal cognitive function in 2009 and 2018 and normal gait speed, grip and no weight loss in 2018 as “control group”. Among them, we extracted 10 age, sex-matched samples randomly from each group and performed targeted metabolomics by the LC/MS/MS Method Package for Primary Metabolites Ver.2 in all 20 serum samples in 2009 and 2018. We compared the activity of the metabolites between the groups and years using t-test and two-way ANOVA.

Results:
Mean age of 20 samples was 70.2±5.5 years old. According to metabolomics, we found that urea increased significantly in frail-like group than in control group, while other metabolites in urea cycle were not changed. In TCA cycle, Aspartate, Aconitate and Succinate decreased in frail-like group compared to control group (Fig 1). Each metabolite activity was not significantly changed over time.

Conclusions:
Increased urea was observed in elderly with frailty. Frailty was associated with not urea cycle itself but urea-associated cycle. That may indicate a possibility of the connection of frailty with urea metabolism change.
Abstract 12172: Trend of Yearly Prevalence and Seasonal Variation of Cardiovascular Diseases With Cancer in Japan
Authors: Morikawa Nagisa , Enomoto Mika , Fukami Ako , Nohara Yume , Nohara Shoichiro , Shibata Tatsuhiro , Shibao Koudai , Ishii Kazuo , Fukumoto Yoshihiro
Published: December 2023

Introduction:
The advance of anticancer therapy increases cardiovascular diseases (CVD) as comorbidity of cancer; however, data regarding cancer comorbidity in CVD patients remains scant. Further, there is a seasonal variation in CVD, but that in CVD with cancer are scarce. Therefore, we examined the trends of yearly prevalence and seasonal variation of CVD with cancer over 9 years using National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB).

Methods:
The NDB sampling dataset were randomly sampled 10% from the whole Diagnosis Procedure Combination (DPC) records extracted and anonymized by Ministry of Health, Labour and Welfare in January, April, July and October from 2011 to 2019. We analyzed each disease which required most medical resource in each patient; I110, I500-519 of ICD-10 code as heart failure (HF), I200-249 as acute coronary syndrome (ACS) and I260, 269 as pulmonary thromboembolism (PTE). We defined CVD prevalence as these CVD (HF, ACS and PTE) records divided by total DPC records, and that of CVD with cancer as CVD records, which included any cancer as comorbidity. Seasonal variation was tested by Chi-square test with a Bonferroni correction.

Results:
Each prevalence of HF, ACS and PTE was increasing (Panel A), decreasing (Panel B) and slightly increasing, respectively. Annual proportions of cancer comorbidity in HF, ACS and PTE were 5.8%, 3.3% and 15.2% and trends of HF and ACS with cancer comorbidity were slightly increasing (Panels D, E), while that of PTE with cancer was not changed. HF, ACS and PTE prevalence were significantly higher in January (winter) than in July (summer); however, the variation of CVD with cancer was diminished (Panels C, F).

Conclusions:
Cancer comorbidity proportion of HF and ACS have been gradually increased, while that of PTE has not changed for 9 years. Seasonal variation was diminished in CVD with cancer. CVD with cancer is expected to be increasing regardless of season.
Abstract 12179: Neutrophil-Specific Deletion of Beta2 Integrins Alleviates Myocardial Ischemia-Reperfusion Injury in Male Mice
Authors: Liu Wei , Cronin Chunxia , Wen Lai , Ley Klaus , Liang Bruce T , Fan Zhichao
Published: December 2023

Neutrophil recruitment and their mediated inflammatory responses are critical for cardiovascular diseases, including myocardial ischemia-reperfusion (I/R) injury, which accounts for 9% mortality and 10% morbidity rates in ischemic heart disease patients. Blocking leukocyte recruitment in mouse knockouts (KO) of beta2 integrin (CD18) or blocking beta2 integrin with antibodies in multiple animals significantly reduced infarct size after myocardial I/R injury. However, the neutrophil-specific contribution of beta2 integrin to I/R injury is unknown. This study used the newly established CD18
flox/flox
(hITGB2 KI) mouse strain to address this knowledge gap. We crossed them to MRP8-cre (S100A8) and confirmed the neutrophil-specific KO of beta2 integrins. Interestingly, all leukocyte subtypes were elevated in the blood of MRP8-cre CD18
flox/flox
mice, indicating potential chronic inflammation. After 35 minutes of myocardial ischemia and 24 hours of reperfusion, we found MRP8-cre CD18
flox/flox
mice have significantly reduced infarct size compared to cre- controls. However, if we distinguish the sex in analysis, we only saw a significant alleviation in male but not female MRP8-cre CD18
flox/flox
mice. The quantification of leukocyte recruitment in hearts after I/R injury showed that male but not female MRP8-cre CD18
flox/flox
mice have less recruitment of neutrophils and Ly6C
high
inflammatory monocytes. These results suggested sex bias of neutrophil-specific contributions of beta2 integrins in myocardial ischemia-reperfusion injury and provided new insights into beta2 integrin targeting therapies.
Abstract 12185: Hypoxia Exacerbates Flow-Induced Vascular Remodeling via CXCL12/CXCR4 Pathway
Authors: Klouda Tim , Tsiki Savas , Liu Tiffany , Kim Yunhye , Visner Gary A , Puder Mark , Raby Benjamin , Yuan Ke
Published: December 2023

Intro:
Patients with congenital heart disease are at risk of developing pulmonary arterial hypertension (PAH-CHD) due to increased blood flow and exposure to hypoxia (Hx). We aimed to establish a“two-hit” mouse model of pulmonary hypertension (PH) combining increased blood flow via left pneumonectomy (LP) and Hx (
Fig 1a
). Our objective was to investigate the pathogenesis of flow-induced vascular remodeling and elucidate the underlying mechanism mediated by smooth muscle cells (SMCs) through the CXCL12/CXCR4 pathway.

Hypothesis:
We hypothesize SMCs contribute to flow-induced vascular remodeling by upregulating the Cxcl12/Cxcr4 pathway.

Methods:
Mice underwent LP followed by 3 weeks of Hx(LP/Hx). PH was evaluated by measuring right ventricular systolic pressure (RVSP) and Fulton Index. Whole lung lobes and precision cut lung slices underwent tissue clearing, immunofluorescence staining and advanced microscopy. SMCs were isolated using Dynabeads and Cxcl12 signaling measured by RT-qPCR. Tissue samples from patients with PAH-CHD (ventricular septal defect) were stained for CXCL12.

Results:
LP/Hx mice demonstrated severe PH compared to Hx controls, as evidenced by increased RVSP (41 vs 33mm Hg), right ventricle hypertrophy (FI: 40 vs 32%) and RV dysfunction (
Fig 1b
). SMCs from LP/Hx mice exhibited an 8.6-fold increase in
Cxcl12
expression compared to controls, with Hx and LP alone showing 5-fold and 2-fold increases, respectively. Advanced microscopy revealed excessive remodeling of distal arterioles in LP/Hx mice (
Fig 1c
). Furthermore, CXCL12 expression was upregulated in SMCs of patients with PAH-CHD compared to controls.

Conclusion:
Our study, using a novel mouse model combining increased blood flow and hypoxia, demonstrated that upregulation of Cxcl12 in SMCs and ECs contributes to flow-induced vascular remodeling. This model has the potential to serve as a pre-clinical model for studying the pathology of PAH-CHD and exploring therapeutic interventions.
Abstract 12216: A Novel Designed Atrial Postero-Septum Linear Ablation Method (Icho Line) for Non-Pulmonary Vein Triggers of Atrial Fibrillation (AF)
Authors: Mukai Yasushi , Kawai Shunsuke , Okahara Arihide , Tokutome Masaki , Matsuura Hirohide , okabe kosuke , Sada Masashi , Itonaga Junpei , Eiichi Koga , Ayano Hara , Kisanuki Hiroshi , Matsukawa Ryuichi
Published: December 2023

Introduction:
Therapeutic strategy for non-pulmonary vein (PV) triggers of atrial fibrillation (AF) has not been well established although they are the major cause of AF recurrence after PV isolation. The atrial postero-septum or right atrial crista terminalis (CT) are the common non-pulmonary vein (PV) trigger sites of atrial fibrillation (AF). For them, a focal ablation is often insufficient due to a regional arrhythmogenicity. We devised an original linear ablation method, named
"Icho Line”
covering the non-PV triggers from this area.

Methods:
Eight hundred and thirty-two AF ablation patients were retrospectively studied. An AF induction test was conducted after each PV isolation procedure. Non-PV triggers were detected in 104 patients (12.7%), among which Icho line ablation was performed in 39 patients (37.5%) with documented triggers of AF from postero-septum or CT. A linear ablation was designed horizontally from the anterior right PV isolation line to fossa ovalis in the left atrium. In the right atrium, the opposite side of the left atrial ablation was continuously ablated toward the CT like the shape of a ginkgo leaf (Figure).

Results:
Atrial tachyarrhythmia recurrence free rate in the Icho line group and other non-PV ablation patients were 61.8% and 45.4%, respectively (P=0.54, Figure). Recurrence with atrial tachycardia was very rare in the Icho line group.

Conclusions:
A novel designed Icho line is a feasible and effective ablation strategy covering non-PV triggers from the atrial septum and CT.
Abstract 12263: Inflammation and Cholesterol as Predictors of Cardiovascular Events and Risk Reduction With Bempedoic Acid Among Statin Intolerant Patients: An Analysis of the CLEAR Outcomes Trial
Authors: Ridker Paul M , Lei Lei , Louie Michael J , Haddad Tariq M , Nicholls Stephen J , Lincoff Abraham M , Libby Peter , Nissen Steven E
Published: December 2023

Introduction:
Among contemporary statin-treated patients, residual inflammatory risk assessed by high-sensitivity C-reactive protein (hsCRP) is a stronger predictor of future cardiovascular (CV) events and all-cause mortality than residual cholesterol risk assessed by low density lipoprotein cholesterol (LDLC). Whether these relationships are present among statin-intolerant patients is unknown but has implications for the choice of preventive therapies including bempedoic acid, an agent that reduces both LDLC and hsCRP.

Methods:
In the multi-national CLEAR-Outcomes trial, 13,970 statin-intolerant patients were randomly allocated 1:1 to 180 mg oral bempedoic acid daily or matching placebo and followed for incident myocardial infarction (MI), stroke, coronary revascularization, CV death, and all-cause mortality. Quartiles of increasing baseline hsCRP and LDLC were assessed as predictors of future adverse CV events after adjustment for traditional risk factors and treatment (bempedoic acid vs. placebo).

Results:
Baseline hsCRP was significantly associated with incident composite endpoint of MI, stroke, coronary revascularization, and CV death (highest vs lowest hsCRP quartile, HR=1.43, 95% CI 1.24-1.65), CV mortality (HR=2.00, 95% CI 1.53-2.61), and all-cause mortality (HR=2.21, 95% CI 1.79-2.73). By contrast, the relationship of baseline LDLC quartile (highest vs. lowest) to future CV events was smaller for the composite endpoint (HR=1.19, 95% CI 1.04-1.37) and neutral for CV mortality (HR 0.90, 95% CI 0.70-1.17) and all-cause mortality (HR 0.95, 95% CI 0.78-1.16) such that risks were high for those with elevated hsCRP irrespective of LDLC level. Compared to placebo, bempedoic acid reduced median hsCRP by 21.6% and mean LDLC levels by 21.1% at 6 months and demonstrated similar efficacy in reducing major adverse CV events across all levels of hsCRP and LDLC.

Interpretation:
Among contemporary statin-intolerant patients, inflammation assessed by hsCRP was a stronger predictor of risk for future CV events and death than was hyperlipidemia assessed by LDLC. Compared to placebo, bempedoic acid had similar efficacy for reducing CV risk across hsCRP and LDLC strata.
Abstract 12275: Neighborhood Deprivation Predicts All-Cause and Cardiovascular Mortality in a Low-Income Population in the Southeastern United States
Authors: Sahinoz Melis , Xu Meng , Deng Kui , Shah Ravi V , Lipworth Loren , Gupta Deepak , Dixon Debra , Shrubsole Martha , Yu Danxia
Published: December 2023

Background:
Neighborhood disadvantage impacts individuals’ morbidity and mortality and contributes to health disparities, but prospective cohort data from individuals of low socioeconomic status (SES) are limited.

Hypothesis:
Greater neighborhood deprivation associates with higher all-cause and cardiovascular (CV) mortality beyond individual SES, lifestyle, and clinical factors in a multi-racial, low-income population.

Methods:
The Southern Community Cohort Study is a population-based cohort of mostly low SES individuals recruited from 12 southeastern US states between 2002-2009. Participant addresses were linked with a census tract-based neighborhood deprivation index (NDI) derived from neighborhood level income, education, employment, housing, and occupation data. Date and cause of death were ascertained via the National Death Index. Cox proportional hazard models were used to test associations between NDI and death adjusted for enrollment age, sex, self-reported race, education, income, insurance, smoking, physical activity, alcohol intake, diet, sleep duration, BMI, and diabetes, hypertension, depression, cancer, heart disease, and stroke.

Results:
Among 79,631 participants, median age was 51 years (25
th
-75
th
percentiles: 45-58), 69% were Black, and 60% were female. Over a median 13-year follow-up, 23,356 participants died, of which 7,214 (30.9%) were CV. With adjustment for age, sex, and race, per standard deviation (SD) increase in NDI was associated with a 19% increase in all-cause mortality (HR 1.19, 95% CI 1.18-1.21) and 16% increase in CV mortality (HR 1.16, 95% CI 1.13-1.19). Even with adjustment for individual SES, lifestyle, and clinical factors, NDI was associated with a 6% increased risk in all-cause mortality (HR per SD increase 1.06, 95% CI 1.03-1.08) and 8% increase in CV mortality (HR 1.08, 95% CI 1.05-1.11). NDI showed similar significant associations with all-cause and CV mortality in Black and White participants.

Conclusion:
Among low-income Americans, greater neighborhood deprivation associates with higher all-cause and CV mortality independent of individual SES, lifestyle, and clinical risk factors. More research is needed to examine factors underlying the health effects of neighborhood deprivation.
Abstract 12293: Subclinical Leaflet Thrombus on Transcatheter Heart Valve in Patients With Severe Aortic Stenosis and Atrial Fibrillation
Authors: Otsuka Yasuhiro , Ishii Masanobu , Ikebe Sou , Tabata Noriaki , Oda Seitaro , Kidoh Masafumi , Shirahama Yuichiro , Egashira Koichi , Kuyama Naoto , Rokutanda Taku , Noda Katsuo , horio eiji , Sakamoto Tomohiro , Kudoh Takashi , Shimomura Hideki , Ikemoto Tomokazu , Tsunoda Ryusuke , Nakamura Taishi , Matsui Kunihiko , Kaikita Koichi , Tsujita Kenichi
Published: December 2023

Background:
Subclinical leaflet thrombosis is one of transcatheter heart valve (THV) failure that should be avoided after transcatheter aortic valve implantation (TAVI). Although the effectiveness of direct oral anticoagulants (DOACs) on subclinical leaflet thrombosis has been demonstrated, there is insufficiently established evidence for post-TAVI antithrombotic therapy. The aim of this study was to clarify the formation process of subclinical leaflet thrombosis on THV and thrombogenicity during the perioperative period of TAVI.

Methods:
This multicenter, prospective, single-arm interventional study enrolled 26 patients with atrial fibrillation treated with edoxaban and severe aortic valve stenosis who underwent TAVI between September 2018 and September 2022. After exclusion, 24 patients were finally analyzed. We investigated changes in maximal leaflet thickness detected by contrast-enhanced computed tomography between 1 week and 3 months after TAVI and measured the thrombogenicity by Total Thrombus-formation Analysis System (T-TAS) and flow stagnation volume by computational fluid dynamics (CFD).

Results:
Of all, subclinical leaflet thrombosis was observed in 16.7% at 1 week, but decreased to 5.9% at 3 months after TAVI. There was no significant difference in maximum leaflet thickness between 1 week and 3 months, however, patients with subclinical leaflet thrombosis at 1 week had a significantly greater difference in that thickness compared to those without thrombosis. Thrombogenicity assessed by T-TAS and platelet count decreased markedly at 1 week and tended to improve at 3 months. Simple liner regression analysis showed that stagnation volume was positively associated with an increase in maximum leaflet thickness, and low-dose edoxaban was associated with a high risk of increased leaflet thickness at chronic phase.

Conclusions:
This study showed that course of leaflet thrombus formation in neo-sinus of THV and dynamic fluctuation of thrombogenicity in the acute phase after TAVI. These findings were merely hypotheses generation and thus necessitate future hypothesis testing with large sample sizes.
Abstract 12306: CREG1 Attenuates Doxorubicin-Induced Cardiotoxicity via Inhibiting the Ferroptosis of Cardiomyocytes
Authors: Liu Dan , Cheng Xiaoli , song haixu , Yan Chenghui , Han Yaling
Published: December 2023

Introduction:
Doxorubicin (DOX) is currently one of the most used anthracycline anticancer drugs. However, the cardiotoxicity of DOX limits its application in cancer patients. Cellular repressor of E1A-stimulated genes (CREG1) is an important cardioprotective factor.

Hypothesis:
We investigated the underlying effects and mechanism of of CREG1 in DOX-induced cardiotoxicity have not been reported.

Methods:
In vivo, a mouse DOX-induced cardiotoxicity model was established by DOX intraperitoneal injection, the mRNA and protein expression of CREG1 in the myocardium was examined using real-time PCR and western blot. CREG1 transgenic mice and cardiac-specific CREG1 knockout mice were used to establish DOX-induced cardiotoxicity model. HE staining, Masson staining, WGA staining and western blot were applied to examine fibrosis, myocardial hypertrophy and ferroptosis. In vitro, neonatal mouse cardiomyocytes (NMCMs) were stimulated with DOX, CREG1 overexpression adenovirus and small interfering RNA was used to examine the role of CREG1 on the ferroptosis of NMCMs.

Results:
In vivo, the mRNA and protein expression of CREG1 were significantly reduced in DOX-treated myocardium. CREG1 overexpression alleviated the myocardial damage induced by DOX, and CREG1 deficiency aggravated the DOX-induced cardiotoxicity. The abnormal increase in ferroptosis was shown in the DOX-treated heart tissues. CREG1 overexpression inhibited the ferroptosis, and CREG1 deficiency aggravated the ferroptosis induced by DOX. In vitro, the mRNA and protein of CREG1 was reduced in DOX-treated NMCMs. CREG1 overexpression reduced the ferroptosis of cardiomyocytes, CREG1 knockdown aggravated the ferroptosis of cardiomyocytes induced by DOX. Mechanically, CREG1 inhibited the mRNA and protein expression of pyruvate dehydrogenase kinase 4 (PDK4). The effect of CREG1 overexpression on ferroptosis of cardiomyocytes was reversed by PDK4 overexpression.

Conclusion:
CREG1 alleviated DOX-induced cardiotoxicity by inhibiting ferroptosis of cardiomyocytes. Our findings might help clarify new roles of CREG1 in the development of DOX-induced cardiotoxicity.
Abstract 12339: Erythropoietin Use in Pediatric Ventricular Assist Device Patients
Authors: Dillon Christina , Godown Justin , Bansal Neha , Amdani Shahnawaz M , Bearl David W
Published: December 2023

Background:
Anemia is common in pediatric ventricular assist device (VAD) patients. Erythropoietin (EPO) has been used to reduce blood transfusions in children after VAD placement. A study in adults showed EPO use after left VAD implantation was associated with higher rates of suspected pump thrombosis. No studies have evaluated the use of EPO in pediatric patients receiving VAD support.

Objectives:
We aim to assess EPO use in all pediatric patients who underwent placement of a VAD and to assess outcomes for children who received EPO compared to those who did not.

Methods:
We identified patients from the Pediatric Health Information System who underwent VAD placement from 2010-2020. Use of EPO was described across all sites. Cohorts were compared to assess differences in blood transfusions received post-VAD, incidence of stroke and pump-exchange. Multivariable Cox proportional hazard and logistic regression models were constructed to adjust for confounding factors for outcomes of VAD exchange and stroke, respectively.

Results:
A total of 1260 patients were included, of which 336 (27%) received EPO. Patients who received EPO were younger (median 3.5y vs. 9y, p<0.001) and more likely to have congenital heart disease (55% vs. 45%, p=0.002). Patients on EPO received fewer blood transfusions compared to those not on EPO [median 0/month (IQR 0-0.9) vs. 0/month (IQR 0-2.3), p<0.001]. VAD exchange and stroke were more common in patients on EPO (10.1% vs. 5.5%, p=0.004 and 37.8% vs. 25%, p<0.001, respectively). After adjusting for confounding factors, the use of EPO was not independently associated with the need for VAD exchange (adjusted hazard ratio 1.2, 95% confidence 0.78 - 1.9, p=0.378). However, EPO remained independently associated with stroke during the hospitalization (adjusted hazard ratio 1.6, 95% confidence 1.2 - 2.1, p=0.002).

Conclusion:
EPO was used in approximately 1 out of 4 pediatric VAD patients. Those who received EPO were younger and more likely to have congenital heart disease. The use of EPO is associated with fewer post-VAD blood transfusions. EPO was not independently associated with VAD exchange but remained independently associated with stroke during the VAD hospitalization.
Abstract 12373: Clinical Outcomes in Patients With Left Ventricular Assist Device on Guideline Directed Medical Therapy: A Propensity Score Matched Analysis
Authors: Rawlley Bharat , Cordova Sanchez Andres , Gupta Kartik , Ramm Matthew , Chaudhuri Debanik
Published: December 2023

Introduction:
We investigate the benefit of Guideline Directed Medical Therapy [GDMT] in patients with Left Ventricular Assist Device (LVAD) using an insurance claims database.

Methods:
We queried Trinetx US collaborative network for patients with LVAD and created two groups; those who received ≥2 prescriptions of any GDMT medication and who did not receive any GDMT after implantation. These were matched by Propensity Score Matching (PSM) for age, race, sex, BMI, LVEF, SBP, DBP, ischemic heart disease, hypertension, disorder of pulmonary circulation, chronic kidney disease (CKD) and acute kidney injury (AKI). All diagnosis were identified using ICD codes. Patient demographics, LVEF, BMI, SBP and DBP were recorded as reported by TriNetX. We looked at primary and secondary outcome measures starting 90 days until 10 years post implantation, primary being all cause mortality and secondary being risk of decompensated heart failure, hypotension, AKI, odds of receiving heart transplant and LVAD explant.

Results:
We had 4514 patients with LVAD on GDMT and 687 without GDMT. After PSM, we had 651 patients in each group. Both were matched by PSM with Standardized mean difference (SMD) < 0.1 for all variables. Those with LVAD on GDMT had lower risk of all-cause mortality [233 (37.28%)] compared to those not on GDMT [157 (56.29%)] (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.24-0.37, P < 0.0001) [Figure 1] but at a higher risk of decompensation (RR 2.74, 95% CI 2.19-3.42), hypotension (RR 3.58, 95% CI 2.73 - 4.69) and AKI (RR 2.64, 95% CI 2.23-3.18). Patients receiving heart transplant and LVAD explant had higher odds of being on GDMT [Odds Ratio [OR], 95% CI: 2.86, 1.87 - 4.37; 4.29, 2.13 - 8.63, respectively).

Conclusions:
LVAD patients on GDMT have lower all-cause mortality, higher odds of receiving heart transplant and LVAD explant starting 90 days post implant. However, for reasons not clear to us, they are also at higher risk of decompensation, hypotension and AKI.
Abstract 12390: Differences in the Impact of Use of Contact Force Sensing Catheters on Subsequent Rates of Pulmonary Vein Reconnection Detected Between Men and Women During Repeat Ablation of Atrial Fibrillation
Authors: Zhang Ruina , Gabriels James , Reznik Elizabeth , Li Han , Mandler Ari , Malkani Kabir , Qu Veronica , Ip James E , Thomas George , Liu Christopher F , Markowitz Steven , Lerman Bruce B , Cheung Jim W
Published: December 2023

Background:
Radiofrequency catheter ablation (CA) is an effective treatment for atrial fibrillation (AF). Contact force (CF) sensing catheters permit tissue contact monitoring that may lead to durable pulmonary vein (PV) isolation.

Objective:
To assess the impact of CF-sensing catheters on PV reconnection rates at repeat AF ablation and whether there are sex-based differences.

Methods:
We conducted a retrospective study of patients who underwent repeat AF ablation after index PV isolation between 2010 and 2022. Patients were divided into 2 groups: Group 1 (non-CF sensing catheters) and Group 2 (CF-sensing catheters).

Results:
One hundred sixty-one patients were included in the study (76 in Group 1 and 85 in Group 2, 32% female, 70 ± 10 years old). Initial use of CF-sensing catheters at index ablation was associated with a lower PV reconnection rate at repeat ablation (60% for Group 2 vs 87% for Group 1; P = 0.001). There were no significant differences in locations of PV reconnection between Group 1 and Group 2. When stratified by sex, there were significantly lower rates of PV reconnection in male patients with use of CF-sensing catheters (92% for Group 1 vs 67% for Group 2; p=0.001) but not for female patients (71% for Group 1 vs 50% for Group 2; p=0.23). On multivariable logistic regression analysis, use of CF-sensing catheters at index ablation (adjusted odds ratio [aOR]: 0.28, 95% CI: 0.12 to 0.65; p=0.003) and female sex (aOR: 0.38, 95% CI: 0.17 to 0.86; p=0.02) were associated with significantly lower rates of PV reconnection found at repeat ablation.

Conclusion:
Use of CF sensing catheters reduced PV reconnection rate found at repeat AF ablation. Females have lower rates of PV reconnection identified at repeat ablation which suggest that non-PV triggers may be a more common cause of recurrent AF, thereby blunting the impact of CF-sensing catheters on reducing recurrent AF in females.
Abstract 12391: Correlation of Admission Heart Rate With MACE Among ST-segment Elevation Myocardial Infarction Patients (killip1) Undergoing Primary Percutaneous Coronary Intervention
Authors: Yang Jian , Zeng Ping
Published: December 2023

Introduction:
Different admission heart rate (AHR) levels are frequently observed in ST-segment elevation myocardial infarction (STEMI) patients. However, it is not clear whether AHR is related to the occurrence of major adverse cardiovascular effects (MACE) after pPCI.

Hypothesis:
We aim to explore the possible correlation between AHR and MACE after STEMI patients receive the primary percutaneous coronary intervention (pPCI).

Methods:
The Chinese STEMI pPCI Registry was registered with ClinicalTrials.gov (NCT04996901). We analyzed 5586 patients with STEMI who underwent pPCI in a multi-center study in China, and patients were grouped according to the AHR greater or less than 70 bpm. Patients’ in-hospital MACE referred to new-onset heart failure and death. The association between AHR and in-hospital MACE was assessed in Logistic regression analysis.

Results:
4004 patients were enrolled ultimately, including 1105 patients with AHR< 70 bpm and 2899 patients with AHR≥ 70 bpm. After multivariate adjustment for age, gender, DBP, HR, smoking, hypertension, et al., the OR of MACE in patients with AHR ≥ 70 bpm was 1.573-1.581 times that of the other group in calibration Model I to IV. Subgroup analysis showed that it was also observed in the young (<60 years old) or the old (≥60 years old), male or female, Left anterior descending (LAD), and Right circumflex artery (RCA) patients (all
P
<0.05). We still found that AHR was a risk factor for in-hospital MACE after excluding those patients with a history of MACE, RCA occlusion and AHR less than 50 bpm or greater than 90 bpm in sensitivity analysis. ROC curve of AHR in predicting the occurrence of MACE after pPCI was 0.699. The cubic spline also confirmed that the risk of MACE decreased significantly with the reduction of AHR.

Conclusions:
In STEMI patients undergoing pPCI, elevated AHR (≥70 bpm) identifies those at increased risk of in-hospital MACE. AHR less than 70 bpm may be a protective factor to avoid the occurrence of MACE.
Abstract 12401: Multidimensional Representativeness of Older Adults With Atrial Fibrillation in Randomized Controlled Trials: Comparing Participants of 12 Oral Anticoagulant RCTs to a Nationally Representative US Cohort
Authors: Shah Sachin J , Anderson Timothy , Cheng David , Ross Joseph S , Hobbs Richard , Connolly Stuart , Ezekowitz Michael D , van Walraven Carl , Singer Daniel E
Published: December 2023

Background:
Anticoagulant RCTs are thought to have enrolled younger and less comorbid patients with atrial fibrillation (AF) compared to the general population. We developed a representation score summarizing patient characteristics to describe how well RCT participants with AF reflect a nationally representative cohort.

Methods:
We studied adults >=65 years old with AF by harmonizing two data sources: (1) patient-level data from 12 landmark RCTs testing anticoagulants vs. placebo or antiplatelets from the Atrial Fibrillation Investigators (AFI) consortium and (2) the Health and Retirement Study AF cohort (HRS-AF), a representative cohort of older adults with AF in the U.S. We fit a logistic regression model to estimate the probability of inclusion in the HRS-AF cohort in the pooled sample using age, height, weight, gender, heart failure, hypertension, diabetes, prior stroke, and prior myocardial infarction. This estimate, the Trial Benchmark Score, reflected the probability of belonging to the HRS-AF cohort and ranged from 0 to 1, with higher scores reflecting a greater likelihood of belonging to the HRS-AF cohort. We plotted the distribution of scores for HRS-AF and AFI participants and compared the mean scores using a t-test.

Results:
Compared to the HRS-AF cohort (n=3542), AFI participants (n=7933) were younger (72 vs. 76yrs, standardized mean difference [SMD] -0.7), more frequently male (64% vs. 46%, SMD 0.3), and had a lower likelihood of prior stroke (19% vs. 23%, SMD -0.4). The mean Trial Benchmark Score differed significantly between the two cohorts (HRS-AF mean 0.47 vs. AFI mean 0.23, p<0.001) (
Figure
). 52% of HRS-AF participants and 12% of AFI participants had a score >0.47 (the HRS-AF mean score).

Conclusion:
Differences in the Trial Benchmark Scores distributions indicate a substantial difference in the distribution of observable characteristics and that RCT participants were not fully representative of the benchmark population.
Abstract 12425: Stim1 Deletion in Treg Cell Protects From HFpEF Pathogenesis
Authors: SRINIVAS BALAJI , Xu Jiang , Peng Hongmei , Sabbah Hani N , Belmadani Souad , Rhaleb Nour E , Matrougui Khalid
Published: December 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is a cardiovascular disease that remains untreatable in its pathogenesis. Therefore, there is a critical need to uncover the cellular and molecular mechanisms underlying HFpEF pathogenesis and identify potential targets for treatment that can enhance cardiac function and restrict disease progression. Previous studies have shown that Treg cells are crucial in hypertension-induced cardiovascular complications and metabolic dysregulation. Moreover, the function of Stromal interaction molecule 1 (STIM1) varies depending on the cell type.

Hypothesis:
We hypothesize that the deletion of STIM1 in Treg cells can protect against the development of HFpEF and its associated conditions.

Methods:
Male mice aged eight weeks (Stim1
flx/flx
and Treg
Stim1-/-
) were divided into four groups: control groups receiving a standard diet and water for five weeks, and HFpEF groups fed a high-fat diet (HFD) and N[w]-nitro-l-arginine methyl ester (L-NAME - 0.5g/L) in the drinking water for five weeks. Various measurements and assessments were conducted, including echocardiography, evaluations of metabolism and hypertension, analysis of heart and kidney injury markers, and assessment of vascular endothelial function.

Results:
After five weeks, Stim1
flx/flx
mice subjected to HFD and L-NAME displayed evidence of HFpEF, including hypertension, metabolic disorders, cardiac hypertrophy with fibrosis, kidney injury with fibrosis, impaired exercise tolerance and vascular endothelial function, increased body weight and E/E' ratio, reduced cardiac index, and unchanged ejection fraction. Interestingly, Treg
Stim1-/-
mice were protected against HFD and L-NAME-induced HFpEF and its associated pathologies.

Conclusions:
These findings underscore the significance of targeting STIM1 in Treg cells to protect from the development and pathogenesis of HFpEF.
Abstract 12426: Effect of Presenting Size on Sex Differences in Ascending Aortic Growth Rate
Authors: Zamirpour Siavash , Boskovski Marko T , Pirruccello James P , Pace William A , Hubbard Alan E , LEACH JOSEPH , Ge Liang , Tseng Elaine E
Published: December 2023

Introduction:
Current guidelines recommend ascending aortic surveillance at 6-24 month intervals regardless of sex. However, emerging evidence suggests that ascending aortic growth is faster in women than men. It is unknown whether this difference is affected by presenting aortic size.

Objective:
To characterize aortic growth by sex and presenting size.

Methods:
The study population consisted of all adults receiving repeated chest computed tomography and/or magnetic resonance imaging at our institution 1994-2022, excluding type A dissections. A custom text processing algorithm was implemented to extract ascending aortic dimensions from radiology reports. Patient-level aortic growth rates were determined by linear regression. Patient-level growth rates were linearly regressed on the interaction of sex and presenting size <4.5 vs 4.5-4.9/5.0-5.4/≥5.5cm, controlling for presenting age. Surveillance intervals at 6, 12, and 24 months were simulated by linear interpolation at the patient level.

Results:
Ascending aortic dimensions were extracted from 7194 scans across 1998 patients (676 [34%] female). Mean (SD) aortic growth was 0.12 (2.0) mm/yr in women and 0.0 (2.0) in men. Excess growth rate in women compared to men was 0.45 mm/yr (95% CI, -0.07 to 0.98, p=0.09) at 4.5-4.9cm, 1.26 mm/yr (0.35-2.17, p=0.007) at 5.0-5.4cm, and 0.83 mm/yr (-0.44 to 2.11, p=0.20) at ≥5.5cm. For surveillance intervals of 6, 12, and 24 months, 25% of women presenting at 4.5-4.9cm would reach 5.5cm after 3, 2, and 1 scan(s), respectively, compared to 11, 6, and 3 scans in men. For presentation at 5.0-5.4cm, 25% of women would reach 5.5cm after one six-month scan, compared to 10, 5, and 3 scan(s) in men for intervals of 6-, 12-, and 24-months.

Conclusions:
While others have reported faster aortic growth with larger size overall, we observed this trend only in larger-presenting women compared to larger-presenting men. Our findings suggest a role for sex- and size-specific aortic surveillance.
Abstract 12439: Abdominal Visceral Fat Area and Density Are Associated With Coronary Artery Calcification: A Cross-Sectional Analysis of the Multi-Ethnic Study of Atherosclerosis
Authors: Haidar Amier , Srikanthan Preethi , Watson Karol E , Allison Matthew A , Kronmal Richard , Horwich Tamara B
Published: December 2023

Introduction:
The associations of body composition components, including muscle and adipose tissue, and markers of subclinical coronary artery disease are unclear. We examined the relationship between abdominal CT-derived measures of the area and density of fat and muscle with coronary artery calcification (CAC), using data from the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods:
A randomly selected total of 1,974 MESA participants free of coronary heart disease underwent abdominal CT scans at exams 2 or 3, with the resulting images interrogated for abdominal body composition. Using six cross-sectional slices spanning L2-L5, Medical Imaging Processing Analysis and Visualization (MIPAV) software was used to determine abdominal muscle and fat composition by utilizing appropriate Hounsfield units (HU) ranges. CT chest scans obtained during the exam 1 were used to obtain CAC scores, calculated using the Agatston method and spatially weighted calcium score (SWCS). Multivariable linear regression analysis was performed to assess the relationship between both abdominal visceral fat and muscle area and density to prevalent CAC.

Results:
A total of 1,089 participants had a CAC>0, with an average CAC score of 310. In the fully adjusted model, for every 10 cm
2
increase in visceral
fat
area, the likelihood of having a CAC >0 increased by 0.60% (p<0.001). In the minimally adjusted model, abdominal
muscle
area was significantly associated with CAC>0, which became non-significant in the fully adjusted model. For density of visceral
fat
, every 1 HU increase (less lipid dense fat tissue), the likelihood of having a CAC score>0 decreased by 0.29% (p<0.05). No significant relationship was observed between density of abdominal muscle and CAC>0.

Conclusion:
Greater area and higher lipid density of abdominal visceral fat was associated with an increased likelihood of having CAC, while there was no significant relationship between abdominal muscle area or density and CAC. Both the quantity and the quality of fat have associations with an important marker of subclinical atherosclerosis, CAC, and their significance with respect to cardiovascular outcomes requires further evaluation.
Abstract 12445: Intracardiac Thrombosis in COVID-19 Inpatients: A Nationwide Study of Incidence, Predictors and Outcomes
Authors: Wang Tom Kai Ming K , Agrawal Ankit , Bajaj Suryansh , Bhagat Umesh , Chandna Sanya , Arockiam Aro Daniela D , Chan Nicholas , Rai Devesh , Badwan Osamah , Shekhar Shashank , Kathavarayan Ramu Shivabalan , Nayar Divya , Jaber Wael A , Griffin Brian P
Published: December 2023

Background:
COronaVIrus Disease 2019 (COVID-19) has been observed to be associated with a hypercoagulable state. Intracardiac thrombosis are potentially serious complications but have seldomly been evaluated in COVID-19 patients. We assessed the incidence, associated factors, and outcomes of COVID-19 patients with intracardiac thrombosis.

Methods:
COVID-19 inpatients during 2020 were retrospectively identified from the national inpatient sample (NIS) database, and data retrieved regarding clinical characteristics, intracardiac thrombosis, and adverse outcomes. Multivariable logistic regression was performed to identify the clinical factors associated with intracardiac thrombosis and in-hospital mortality and morbidities.

Results:
A total of 1,683,785 COVID-19 inpatients were identified in 2020 from NIS, with mean age of 63.8±1.6 years and 32.2% were females. Overall in-hospital outcomes include all-cause mortality 13.2% (222,695/1,683,785), cardiovascular mortality 3.5%, cardiac arrest 2.6%, acute coronary syndrome (ACS) 4.4%, heart failure 16.1%, stroke 1.3% and acute kidney injury (AKI) 28.3%. Intracardiac thrombosis was present in 0.001% (1,830) patients. The main factors associated with intracardiac thrombosis were history of congestive heart failure, stroke, coagulopathy and male sex. Intracardiac thrombosis was independently associated with a higher risk of in-hospital all-cause mortality (OR: 3.32, 95%CI: 2.42-4.54, p<0.001), cardiovascular mortality (OR: 2.95, 95%CI: 1.96-4.44, p<0.001), cardiac arrest (OR: 2.04, 95%CI: 1.22-3.43, p=0.006), ACS (OR: 1.62, 95%CI: 1.17-2.22, p=0.003), stroke (OR: 3.10, 95%CI: 2.11-4.56, p<0.001), and AKI (OR: 2.13 95%CI: 1.68-2.69, p<0.001), but not incident heart failure (p=0.27).

Conclusion:
Although intracardiac thrombosis is rare in COVID-19 inpatients, its presence was independently associated with higher risks of in-hospital mortality and most morbidities. Prompt investigations and treatments for intracardiac thrombosis are warranted when there are high index of suspicion and a confirmed diagnosis respectively.
Abstract 12479:

Cardiovascular Stroke Nursing Best Abstract Award:

Sex Differences in Relationships Between Inflammation and Symptoms in Persons With Heart Failure
Authors: Butts Brittany , Davis Erica , Morris Alanna A , Dunbar Sandra B
Published: December 2023

Background:
Heart failure (HF) is a complex syndrome involving interplay of pathologic processes, such as inflammation and myocardial remodeling. Sex differences in cardiac remodeling and function are linked to differences in inflammation. Female hearts show a pro-inflammatory shift and increased cytokine expression with aging not seen in male hearts. Yet, sex is not often considered in HF interventions. Previous studies suggest sex may moderate the relationship between inflammation and symptoms in cardiometabolic disease, but the relationship in HF is unknown.

Purpose:
To examine sex differences in inflammation and symptoms in Black adults living with HF.

Methods:
Black adults living with HF (N=41) were enrolled in this pilot study. Physical symptoms were measured with PROMIS Dyspnea, Heart Failure Somatic Perception Scale (HFSPS), and Multidimensional Fatigue Inventory (MFI). Mood symptoms were measured with Center for Epidemiological Studies Depression Scale (CESD), State-Trait Anxiety Inventory (STAI), and Perceived Stress Scale (PSS). Inflammatory biomarkers were measured via multiplex immunoassay. Xanthine oxidase (XO) activity, an indicator of oxidative stress, was measured via ELISA. Pearson correlations were stratified by sex.

Results:
The mean age was 57 ± 11 years, and 66% were female. Dyspnea was positively associated with XO activity in both groups. Among females, dyspnea was positively associated with matrix metalloproteinase (MMP)-12 (r=.519, p=.033), interleukin (IL)-6 (p=.564, p=.018), [C-C motif chemokine ligand(CCL)-3, (r=.509, p=.037), and CCL-11 (r=.520, p=.032). HFSPS was positively associated with XO activity among females only (r=.445, p=.014). CCL-11 was positively associated with MFI (r=.616, p=.008), PSS (p=.0537, r=.032), STAI (r=.714, p=.001), and CESD (r=.635, p=.008) symptoms among females but not males.

Conclusions:
While physical symptoms were associated with similar inflammatory pathways, fatigue and mood symptoms were associated with inflammation among females only. Women may be more vulnerable to inflammation-induced mood changes and fatigue. Further work is needed to better understand how sex modulates the relationship between inflammation and symptoms in persons with HF.
Abstract 12489: Sex Differences in Incidence and Outcomes of Patients With New-Onset Post-Transplant Diabetes Mellitus After Heart Transplantation
Authors: Chung Alice , Hartman Heidi , Golob Stephanie , Concha Daniella , Batra Jaya , DeFilippis Ersilia , Sayer Gabriel T , Latif Farhana , Yuzefpolskaya Melana , Raikhelkar Jayant , Fried Justin A , Takeda Koji , Uriel Nir , Clerkin Kevin
Published: December 2023

Introduction:
Post-transplant diabetes mellitus (PTDM) is a common complication following heart transplantation (HT), mostly commonly occurring in the first year after transplant. A few risk factors for the development of PTDM have been identified, including immunosuppressive medications such as calcineurin inhibitors and glucocorticoids. Some studies have suggested that among HT recipients, women have higher rates of acute rejection which may necessitate higher doses of steroids and further hyperglycemia. However, differences between sexes in the incidence of PTDM after HT have not been established.

Methods:
A retrospective review of patients who underwent HT at a large-volume center between January 1, 2010 and December 31, 2019 was performed. Patients undergoing re-transplantation or dual-organ transplantation were excluded. PTDM was defined as hemoglobin A1C≥6.5% or a random glucose >200 after HT among patients with no prior history of DM. Predictors of PTDM by sex were analyzed with logistic regression, and post-transplant outcomes were analyzed with Chi-Square analysis.

Results:
Among 317 transplant patients without pre-transplant DM, 71 (22.4%) patients were identified who had PTDM: 24 females (33.7%), 47 males (66.2%). There were no statistically significant differences in baseline characteristics between males and females who developed PTDM including age, race, pre-transplant HTN, calcineurin or steroid dosing at 1 month and 1 year post-transplant. Baseline HTN (OR 2.9, [1.3, 6.7], p=0.009) and mean steroid dose over the first 2 years post-transplant (OR 1.2, [1.0, 1.3], p=0.006) were predictors of PTDM in females but not in males, and mean tacrolimus dose was a predictor in males (OR 1.1, [1.0, 1.2], p=0.001) but not in females. Time to PTDM diagnosis did not differ by sex (log-rank p=0.56). Additionally, post-transplant outcomes in patients with PTDM including acute cellular rejection, antibody-mediated rejection, coronary allograft vasculopathy and death did not differ by sex.

Conclusion:
PTDM is a common complication of HT. Our study suggests that risk factors for PTDM among HT recipients differ by sex. Future studies should investigate the mechanisms underlying these differences to further guide sex-specific post-HT care.