bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18360: Single-Cell Analysis Reveals Insights Into Visceral Adiposity in Mice With Diabetes-Associated Atherosclerosis
Authors: Jamaiyar Anurag , Chen Jingshu , Feinberg Mark W
Published: December 2023

Introduction:
- Visceral white adipose tissue (vWAT), once considered passive and uniform, is a dynamic and heterogeneous tissue involved in glucose and lipid metabolism and immune response. Changes in adipose tissue morphology, physiology, and cellular composition occur in response to dietary fat and carbohydrates, associated with insulin resistance, dyslipidemia, and type 2 diabetes. vWAT also has implications for vascular diseases such as atherosclerosis. However, the connection between vWAT metabolism and atherosclerosis in mouse models remains to be fully elucidated.

Methods:
- vWAT from male
Ldlr
-/-
mice fed either a chow diet or high fat, high sucrose containing (HFSC) diet for 24 weeks were harvested. Single cell RNA sequencing, histology and immunofluorescence were used to analyze the cellular and transcriptomic profiles in the chow and HFSC groups.

Results:
- We identified distinct subpopulations of vascular endothelial cells (ECs), immune cells, and adipose stem and progenitor cells (ASPCs), revealing differences between healthy and diseased groups. Notably, we observed a significant increase in immune cell composition, accompanied by a decrease in ECs and progenitor cells in HFSC-fed mice. Within the macrophage population, we noted increased activated macrophages, B-cell derived macrophages, and collagen-expressing macrophage subclusters. In ECs, we observed increased lymphatic and vascular EC subgroups. Furthermore, inflammation and altered metabolism pathways were found in both macrophage and ECs. We identified novel markers, such as Lyz2 and Trem2, that were highly associated with diabetes associated atherosclerosis in male

Ldlr
-/-

mice. Through cell-cell interaction analysis (CellChat), we discovered distinct interactions patterns associated with enriched pathways such as chemokine, Wnt, and BMP signaling in multiple cell types, including macrophages, mesothelial cells, ASPCs, pericytes, SMCs, and ECs.

Conclusion:
Our scRNAseq atlas reveals interactions amongst adipose cell types in lean and obese states, with the chemokine pathway emerging as a prominent player. This dataset serves as a valuable resource for studying genes and cell types involved in vWAT function in diabetes-associated atherosclerosis.
Abstract 18362: Endovascular versus Surgical Revascularization for Chronic Limb Threatening Ischemia: A Comparison of Re-Admission Rates From NSQIP Database (2011-2021)
Authors: Mufarrih Syed H , Qureshi Nada , Khan Mohammad Saud , McCurdy Matthew , Haider Sajjad , Akbar Muhammad , Kazimuddin Mohammed , Aronow Herbert D
Published: December 2023

Background:
Data regarding relative readmission rates following endovascular and surgical revascularization for chronic limb threatening ischemia (CLTI) are conflicting. Understanding comparative readmission rates may inform selection of the most appropriate revascularization modality for these patients.

Research Question:
What are the differences in 30-day readmission rates between endovascular and surgical interventions for CLTI?

Methods:
The 2012 to 2021 American College of Surgeons National Surgical Quality Improvement Program's (NSQIP) Targeted Vascular Module was used to identify patients discharged alive after surgical or endovascular revascularization for CLTI. The primary outcome was 30-day readmission following the index procedure; secondary outcomes included survival, major re-intervention of the treated arterial segment, amputation, untreated loss of patency of bypass graft, bleeding requiring transfusion or re-intervention, major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Revascularization modality was related to 30-day readmission using multivariable logistic regression.

Results:
We identified 30,390 patients (mean age 69±11.5 years, male 62.8%, mean BMI 26.9±8.1 kg/m
2
, 61% Caucasian, 20.2% Black). When compared with endovascular therapy, surgical bypass was associated with higher 30-day readmission (13.3% vs. 8.6%, p = <0.001). After adjusting for demographic, clinical, procedural variables and year of publication, surgical revascularization was independently associated with higher 30-day readmission rates (OR 1.53 95% CI [1.36, 1.71]; p<0.001), mortality and major reintervention rates (Figure).

Conclusion:
Surgical revascularization was independently associated with higher 30-day readmission rates when compared to endovascular revascularization for patients with CLTI.
Abstract 18363: Readmission & Temporal Trends of Post LVAD Placement Complications in Patients With End-Stage Heart Failure
Authors: Eltawansy Sherif , Udongwo Ndausung , Dandu Sowmya , Akhlaq Hira , Johal Anmol , Mararenko Anton , Alrefaee Anas , Alshami Abbas , Almendral Jesus , Heaton Joseph
Published: December 2023

Introduction:
5-10% of heart failure (HF) patients progress to advanced stages. Left ventricular assist devices (LVADs) have emerged as a favored therapy for end-stage HF as destination therapy or as a bridge to heart transplantation. However, complications and provider expertise hinder its widespread use. Third generation LVAD was introduced in 2018 to enhance usability and reduce complications. We aim to investigate the temporal trends in post-LVAD complications with the latest generation LVAD vs the previous version.

Methods:
We utilized the 2016-2020 Nationwide Readmission Database to identify patients ≥ 18 years of age with advanced HF implanted with an LVAD. Variables were identified using International Classification of Diseases, Tenth revision codes. We compared 2 groups based on the implant year (2016-2018 and 2019-2020). The primary outcome was 30-day readmission (30-dr), while secondary outcomes were trends in complications, mortality rate, and healthcare cost. Multivariate analyses and descriptive bivariate analyses were performed. A p-value <0.05 was considered statistically significant.

Results:
We identified 7,975 patients (21.3% females) of which 17.1 % (n = 1,214) were readmitted within 30 days. Readmission rates were 17.7% (n = 778) for 2016-2018 and 16.2% (n = 435) for 2019-2020 (adjusted Wald test, p = 0.26). The 2019-2020 group exhibited lower rates of cardiac device complications, vasopressor usage, cardiac tamponade, and peri-procedural circulatory complications than the 2016-2018 group (adjusted Wald test, p < 0.05). No significant differences in mortality or LOS were observed between the two groups (adjusted Wald test, p > 0.05). Healthcare costs were higher in the 2019-2020 group (mean $276,439 vs $315,332, adjusted Wald test, p = 0.01).

Conclusions:
Complications following LVAD placement continue to impede broader adoption for advanced HF. Nonetheless, advancements in newer LVAD generations and improved provider expertise hold promise for increased utilization. Our study indicates a decline in complications, including cardiac tamponade and post-procedural complications, which may be attributed to newer device innovations. Further research is necessary to explore this correlation in greater depth.
Abstract 18371: Evaluation of the Atrial Fibrillation Better Care Pathway in Patients With Atrial Fibrillation: A Machine Learning Cluster Analysis
Authors: Wang Jingyang , Bian Haiyang , Yang Yanmin , Xuegong Zhang
Published: December 2023

Background:
Atrial fibrillation Better Care (ABC) pathway is recommended by guidelines on atrial fibrillation (AF) and exerts a protective role against adverse outcomes of AF patients. We hypothesize that cluster analysis, an unsupervised machine learning technique, could comprehensively evaluate multiple clinical characteristics of patients, and define clusters of ABC criteria efficacy in patients with AF.

Methods:
We used data from an observational cohort that included 2,016 patients with AF. We utilized 46 baseline variables for cluster analysis and got the optimal clusters through the K-prototypes algorithm. We evaluated the management patterns and adverse outcomes of identified phenotypes. We assessed the effectiveness of the ABC criteria in reducing adverse outcomes of these phenotypes.

Results:
Cluster analysis identified AF patients into three distinct groups with markedly different clinical characteristics and outcomes. The clusters were as followed: Cluster 1, old patients with atherosclerotic-comorbidities (n = 964); Cluster 2, young females with valve-comorbidities (n = 407), and Cluster 3, paroxysmal AF patients with low comorbidities (n = 644). The clusters showed significant differences in MACNE, all-cause death, stroke, cardiovascular death, and hospital readmission for heart failure. All clusters showed that full adherence to the ABC pathway was associated with a significant reduction in the risk of MACNE (all P< 0.05). Adherence to the different ‘A’/’B’/’C’ criteria alone showed differential clinic impact for three clusters.

Conclusion:
Cluster analysis of the Chinese AF cohort further elucidated the heterogeneity of AF. We proposed suggestions for optimizing risk stratification and integrated management of AF patients.
Abstract 184: Blood Pressure Matters After Cardiac Arrest: Is Our Target Too Low?
Authors: Beekman Rachel , Kim Noah , Kitlen Eva , Choy Courtney , Stendahl John , ANENI EHIMEN , Kwan Jennifer , Wira Charles R , Mcginniss George , Khosla Akhil , Miller P. Elliott , Greer David M , Petersen Nils H , gilmore emily j
Published: December 2023

Introduction:
Blood pressure is an important therapeutic target after cardiac arrest (CA), crucial for maintaining cerebral blood flow and preventing secondary brain injury. However, the optimal blood pressure during the post-resuscitation period remains unknown.

Hypothesis:
Proportion of time with mean arterial pressure (MAP) below a specific threshold will be associated with worse clinical outcomes.

Methods:
We assessed a retrospective cohort of CA patients admitted to an academic center between January 2014 - August 2022. Patients without a documented initial MAP, those who progressed to brain death, or who died within 96 hours were excluded. Multivariable logistic regression was used to test associations between proportion of time with MAP < 65mmHg or < 80mmHg and outcomes [survival and good neurologic outcome (Cerebral Performance Category 1-2) at hospital discharge]. We adjusted for age, sex, Charlson Comorbidity Score, CA location, initial rhythm, Pittsburgh Cardiac Arrest Category, and peak 24h norepinephrine equivalent. We evaluated the initial 96 hours from CA and the following sub-periods: 1) 0-24h, 2) 25-72h, and 3) 73-96h.

Results:
Of 817 patients with CA, 411 were included. Over the initial 96 hours, the proportion of time with MAP < 80 was inversely associated with survival and good neurologic outcome (adjusted OR [95% CI] per 10% time 0.83 [0.75 - 0.93] and 0.78 [0.69 - 0.89], respectively); no such association was found for MAP < 65. This inverse association held in period 2 (0.85 [0.78-0.93] and 0.79 [0.71-9.88], respectively) and period 3 (0.87 [0.80-0.94] and 0.85 [0.78-0.93], respectively), but not in period 1 (Figure 1).

Conclusion:
The proportion of time spent with MAP < 80mmHg was associated with worse outcomes, independent of disease severity. The neuroprotective effect of higher MAP appears to occur between 25-96h from CA. Future prospective studies are needed to further characterize the differential clinical impact of MAP across time.
Abstract 18422: Long-Term Changes in Tricuspid Regurgitation and Right Ventricular Function in Patients Undergoing Lung Transplantation: A 5-Year Study
Authors: Karmali Rehan , Hariri Essa , Honnekeri Bianca , Noall Olivia , BUDEV MARIE , McCurry Kenneth , Menon Venu
Published: December 2023

Introduction:
The presence and severity of tricuspid regurgitation (TR) has been associated with cardiovascular morbidity and mortality in a number of disease states. The impact of TR on future outcomes in patients selected for lung transplantation has not been adequately evaluated.

Methods:
We retrospectively evaluated patients who underwent lung transplant at Cleveland Clinic between 2000 and 2022. Patients undergoing multi-organ transplant, CABG, surgery or valve repair were excluded. The presence of baseline TR and its severity was assessed on the closest echo antecedent to transplantation utilizing an IRB approved Echocardiography registry. We used survival analyses to assess our primary outcome of all-cause mortality. We also assessed distribution of TR severity over short and long-term follow up.

Results:
We evaluated pre-transplant echocardiograms in 1490 individuals who had a mean age of 55 years; 60% being female. The proportion of 0, 1+, 2+, 3+ and 4+ TR was 56%, 25%,12%, 4% and 3% respectively. During a 5-year post-transplant follow-up period, the presence of severe TR pre-operatively was associated with an increased risk for all-cause mortality [aHR 2.1, 95% CI (1.09, 5.1); p = 0.029]. The distribution of TR severity did not appear to be significantly modified by the procedure at 6, 12, 24, 36, 48 and greater than 48-month follow up [OR 1.32, 95% CI (1.76), p = 0.062).

Conclusions:
Pre-operative TR severity as measured by echocardiography was associated with an increase in all-cause mortality in patients undergoing lung transplant, but the distribution of TR severity did not significantly differ on long-term post-transplant follow up.
Abstract 18428: Effect of Continuous Positive Airway Pressure on Atrial Remodeling in Patients With Obstructive Sleep Apnea and Paroxysmal Atrial Fibrillation; a Randomized Controlled Trial
Authors: Hunt Tove Elizabeth F , Traaen Gunn Marit , Massey Richard J , Aakeroy Lars , Bendz Christina , Øverland Britt , Akre Harriet , Steinshamn Sigurd , Loennechen Jan Pål , Broch Kaspar , Lie Øyvind H , Helle-Valle Thomas , Anstensrud Anne Kristine , Hermann Haugaa Kristina , Gullestad Lars , Anfinsen Ole-Gunnar , Aakhus Svend
Published: December 2023

Introduction:
Obstructive sleep apnea (OSA) is known to cause left atrial (LA) remodeling. The effect of continuous positive airway pressure (CPAP) on LA remodeling in patients with OSA and paroxysmal atrial fibrillation (AF) has not been assessed.

Hypothesis:
We aimed to assess the impact of CPAP treatment on reverse LA deformation and volume in patients with AF and OSA.

Methods:
In this secondary analysis of a prospective randomized controlled trial, we screened patients with AF for OSA. The majority of patients were referred for pulmonary vein isolation (PVI). We included AF patients with OSA defined as apnea-hypopnea index (AHI) > 15/h. Patients were randomized to CPAP treatment or standard care. Transthoracic echocardiography was performed to assess atrial remodeling by two-dimensional speckle tracking LA reservoir strain (by AFI LA) and LA volume index (LAVI) in apical 2- and 4-chamber views in sinus rhythm at baseline and at 12 months’ follow-up by an investigator blinded to allocated arm. AF burden was monitored by an implantable loop recorder in all patients.

Results:
We included 104 patients (62 ±7 years old, 77% men, BMI 30 ± 4) of whom 50 were randomized to CPAP and 54 to standard care. PVI was performed in 83 patients six months after the baseline exam. There was no clear improvement in LA reservoir strain in either group from baseline to follow up (CPAP: 30 ± 8 % vs 32 ± 9 %, p = 0.15; standard care: 28 ± 7 % vs 30 ± 6 %, p = 0.11), and there was no difference between the groups (p=0.41). Similarly, LAVI did not change in the CPAP group (38±8 mL/m
2
vs 36± 10ml/m
2
, p= 0.16) or in the standard care group (39± 10 mL/m
2
vs 37 ± 12 ml/m
2
, p= 0.20) during follow-up, with no difference between the two groups (p =0.62). In patients who underwent PVI, the AF burden decreased in both treatment arms, with no between-group difference (p = 0.69).

Conclusions:
In AF patients with OSA, treatment with CPAP did not improve reverse left atrial remodeling within 12 months. Although the trial was relatively small, these results suggest that CPAP is unlikely to have a major impact on normalization of LA function after atrial fibrillation ablation in this patient group.
Abstract 18432: Lipoprotein(a) is Associated With Long-Term Plaque Progression, Pericoronary Inflammation and High-Risk Plaque on Serial Coronary CT Angiography
Authors: Nurmohamed Nick , Gaillard Emilie , Malkasian Shant , Bom Michiel J , de Groot Robin , Ibrahim Shirin , Jukema Ruurt , Kaiser Yannick , Min James K , Earls James , Planken R. Nils , Choi Andrew , Stroes Erik S , Knaapen Paul
Published: December 2023

Background
This study investigated the effect of lipoprotein(a) (Lp[a]) on long-term plaque progression, high-risk plaque (HRP) and pericoronary adipose tissue attenuation (PCATa) in patients suspected of coronary artery disease.

Methods:
Per-protocol, patients from a coronary CT angiography (CCTA) cohort (Diemen et al., 2021) were invited for repeat CCTA imaging, regardless of symptoms. A total of 299 patients underwent follow-up CCTA imaging with a median scan interval of 10.2 [IQR 8.7-11.2] years. Patients who underwent coronary artery bypass grafting and vessels revascularized by percutaneous coronary intervention were excluded. Scans were analyzed using atherosclerosis-imaging quantitative CCTA (AI-QCT; Cleerly Inc.). The associations between high (Tertile 3; >67 nmol/l) and low Lp(a) (Tertile 1 and 2; ≤67 nmol/l), baseline and follow-up plaque burden and characteristics were evaluated using multivariable regression adjusted for clinical risk factors, statin use and scanner settings.

Results:
In total, 274 patients were included, mean age was 57±7 years, 42% were women. Patients with high Lp(a) levels had higher volumes of percent atheroma volume (PAV) at baseline and follow-up and higher rate of plaque progression (Figure 1A). The difference in PAV caused by high Lp(a) versus low Lp(a) patients was similar to the effect of a 12-year age difference. At baseline, patients in the highest tertile of Lp(a) levels had a higher prevalence of both HRP (OR 2.24; p=0.009) and above-median right coronary artery PCATa (OR 1.76; p=0.049). Finally, patients with high Lp(a) levels had a twofold higher incidence of major adverse cardiovascular events (MACE; Figure 1B; p=0.044).

Conclusion:
Patients with high Lp(a) levels had increased coronary plaque burden, increased prevalence of high-risk plaque and pericoronary inflammation as well as increased plaque progression leading to an increased incidence of MACE throughout 10-year follow-up.
Abstract 18446: Rates and Risk Factors of Pregnancy-Related Ischemic Stroke During Labor Admissions
Authors: Ghanem Fares , Alhuneafat Laith , jabri ahmad , Alameh Anas , Aburumman Huthaifah , Poornima Indu G
Published: December 2023

Background:
Pregnancy-related stroke is a relatively uncommon yet devastating complication. However, the rates and associated risk factors of stroke in this context remain poorly described.

Hypothesis:
We aim to evaluate rates and associated risk factors for stroke.

Methods:
We conducted a population-based retrospective study using national inpatient data from 2016 to 2020 to assess ischemic stroke rates and identify associated risk factors during labor admissions. Regression analysis was performed, adjusting for multiple patient characteristics, to determine significant factors related to stroke occurrence.

Results:
We examined a total of 19,089,780 labor admissions. The incidence of ischemic stroke during labor admissions was recorded at a rate of 445 per 100,000 cases. Several factors showed significant associations with ischemic stroke in this context. Atrial fibrillation exhibited a strong correlation (odds ratio [OR] 5.98, 95% confidence interval [CI] [1.16-30.92], p=0.033), as did dyslipidemia (OR 9.54, 95% CI [4.38-20.80], p<0.001), heart failure (OR 3.95, 95% CI [1.09-14.34], p=0.037), chronic kidney disease (OR 6.27, 95% CI [1.92-20.47], p=0.002), cesarean section (OR 2.23, 95% CI [1.60-3.13], p<0.001), chronic hypertension (OR 1.67, 95% CI [1.12-2.47], p=0.011), and hypertensive disorders of pregnancy (OR 7.00, 95% CI [4.94-9.44], p<0.001). However, factors such as advanced maternal age, race/ethnicity, income quartile, gestational and non-gestational diabetes mellitus, coronary artery disease, tobacco use, polycystic ovarian syndrome, and peripartum cardiomyopathy did not exhibit significant associations with stroke.

Conclusion:
Our study highlights an incidence rate of 445 per 100,000 cases for pregnancy-related ischemic stroke during labor admissions and identified certain associated risk factors. These findings provide valuable guidance to healthcare professionals in identifying high-risk individuals.
Abstract 18465: Regulation of Collagen Synthesis and Fibrosis Development in Skeletal Muscle by La-Related Protein 6 (LaRP6)
Authors: Yoshida Tadashi , Lott C. S , Sukhanov Sergiy , Delafontaine Patrice
Published: December 2023

Introduction:
Excessive extracellular matrix (ECM) accumulation, especially collagens, impairs muscle function in muscular dystrophies, aging and muscle trauma (fibrosis). We have found increased skeletal muscle fibrosis in congestive heart failure (CHF) conditions, likely contributing to the impaired muscle functions.

Hypothesis:
We hypothesized that LARP6 (La Ribonucleoprotein Domain Family Member 6), an mRNA binding protein that coordinates efficient translation of Collagen I α chains, regulates collagen synthesis during skeletal muscle fibrosis in CHF conditions.

Approach:
Skeletal muscle fibrosis was analyzed in two mouse models, angiotensin II (Ang II) infusion and left anterior descending artery (LAD) ligation. Expression and subcellular localization of Collagen I, Larp6 and myogenic markers (myogenin and Myh3) were analyzed by qRT-PCR, western blotting, in situ hybridization (RNAScope) and immunostaining in hindlimb muscles
in vivo
and primary myoblasts and fibro/adipogenic progenitor (FAP) cells
in vitro
. Collagen I levels were also analyzed by picrosirius red staining (PSR). These analyses were performed in a newly-generated Larp6 knockout (Larp6
-/-
) mice.

Results:
In both Ang II and LAD ligation models, Collagen I mRNA and protein levels were increased together with LARP6, suggesting that LARP6 may regulate Collagen I synthesis in these conditions. In cultured myoblasts and FAPs, LARP6 protein was co-localized with Col1a1 mRNA at endoplasmic reticulum (ER). TGF-β treatment increased the LARP6 and Col1a1 mRNA co-localization, associated with increased pro-collagen I protein levels. Although Larp6 deficiency did not alter basal Collagen I levels, Collagen I induction in fibrotic conditions was decreased in Larp6
-/-
mice. We found that thick collagen

fibers were more significantly decreased compared to intermediate or loosely-packed thin collagen fibers (PSR signal analysis under the polarized microscope).

Conclusions:
These data suggest that LARP6 regulates Collagen I protein synthesis and its filament assembly likely in ER by binding to Col1a1 mRNA upon fibrosis induction. Suppression of LARP6 may be a therapeutic strategy to prevent pathophysiological fibrosis development in skeletal muscle.
Abstract 18474: Impact of the Endothelial Nucleotidase on Vascular Function
Authors: Gordon Kyle J , Bermeo-Blanco Oscar , Gorr Matthew , Covarrubias Roman , Gumina Richard J
Published: December 2023

Introduction:
Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide. Endothelial dysfunction—marked by poor endothelial-derived vasodilation—is a major prelude to atherosclerotic cardiovascular disease. Endothelial cells (EC) play a vital role in modulating thrombosis, atherosclerosis, and blood flow. One tool the endothelium uses to communicate with surrounding tissues is purinergic signaling. EC express both purinergic receptors to respond to stimuli and ectonucleotidases to facilitate this communication. CD39 is believed to be vital in maintaining homeostasis within the vasculature as it is an ectonucleotidase responsible for converting extracellular ATP and ADP into AMP. However, little is known about the role of endothelial expressed CD39 on vascular function.

Hypothesis:
We hypothesized that the absence of endothelial CD39 causes an elevation in extracellular adenine-nucleotides, thus causing an elevated endothelial-derived vasodilatory response.

Methods:
We generated a novel cre-lox endothelial cell-specific CD39 knockout mouse model (
Tie2cre+ CD39flox/flox
) to explore the enzyme’s role in vascular physiology. After validation via flow cytometry and enzyme activity assays, we assessed mouse blood pressure along with EC-derived vasodilatory capacity. Coronary vasodilatory capacity or coronary flow reserve (CFR) was measured via an isoflurane-induced-vasodilation coronary flow model and imaged using transthoracic ultrasound.

Results:
We noted that the EC specific CD39 knockout mice (EC-cKO) exhibited significantly lower systolic, diastolic, and mean arterial blood pressures at baseline, showing the EC-cKO mice having reduced pressures of over 10mmHg compared to wild-type (EC-WT) (p<0.05). This suggested fundamental differences in vascular function, prompting assessment of CFR. The EC-cKO mice showed a 75.9% increase in CFR (p<0.05) compared to wild-type (EC-WT).

Conclusions:
The loss of CD39 on EC leads to an overall protective phenotype—EC-cKO mice show drastically lower blood pressures, likely due to improved vasodilatory capacity under healthy conditions. This study shows CD39 inhibition’s potential as a therapeutic target in terms of improving vascular function.
Abstract 18503: Endogenously Released Factors From Doxorubicin-Treated Breast Cancer Spheroids Contribute to Toxicity in Human Cardiomyocytes: Protective Effect of Combination Therapy With PDE5-mTOR Inhibitors
Authors: Das Anindita , Bhuiyan Nuhash , Kodali Varun , Lau Valerie , Chakravarty Simi , Samidurai Arun , Kukreja Rakesh C
Published: December 2023

Background:
We previously demonstrated that a novel combination therapy with the phosphodiesterase 5 (PDE5) inhibitor (sildenafil, Sild) and mTOR inhibitor (rapamycin, Rapa) potentiates doxorubicin (DOX)-induced breast cancer cell killing, but attenuates cardiotoxicities. However, it remains unclear whether there are any factors released from cancer cells treated with DOX that contribute to the injury in cardiomyocytes, which can be modified by Sild and Rapa in combination. Therefore, we designed experiments using spheroid cultures of breast cancer and human AC-16 cardiomyocytes to determine the role of endogenously released factors following treatment with DOX.

Methods & Results:
Spheroid cultures of breast cancer MDA-MB-231 cells were treated with DOX (1 μμ), and/or Sild (10 μμ) and Rapa (100 nμ) for 48 hours. The medium was replaced and spheroids were further incubated for 48 hours in the fresh medium. Thereafter, the AC-16 cardiomyocytes were treated with the medium from drugs-treated spheroids for 48 hours. Our results showed that treatment with DOX and/or Sild and Rapa was highly effective in reducing the size of spheroids as compared to the control (
Fig. A
). Moreover, Western blots showed that p-mTOR/mTOR and p-S6/S6 were induced and p-AKT/AKT was suppressed after DOX treatment in cancer cells, which were normalized following treatment with Sild and Rapa (
Fig. B
). The medium from DOX-treated spheroids caused increase of cardiomyocytes death as assessed by trypan blue exclusion assay, which was attenuated by co-treatment with the medium from Sild and Rapa treated spheroids (
Fig. C
).

Conclusion:
These results suggest that cardiotoxicity of chemotherapeutic agents could be partly contributed by the endogenously released unknown factors from tumors, which can be modulated by a novel combination treatment with Sild and Rapa via regulating mTOR-signaling pathways.
Abstract 18508: Usability of Novel Automated Software for Guiding Remote Titration of Antiarrhythmic Drugs
Authors: Navara Rachita , Paudel Bishow M , Ananth Esha , Sujay Sheth , Devgun Jasneet , Lucy Daniel , Chen Devon , Pallod Aditi , Dopierala Maria , Ravuri Riya , Ozkan Ecem , Kheiri Babikir , Malcolm Katherine , Venkateswaran Ramkumar , Martinez Alejandro Alvarez , DeLeon Rania , Higgins John , Patel Kunj G
Published: December 2023

Introduction:
We tested the first novel software application to accurately measure QTc using a machine learning algorithm from a mobile ECG and recommend patient-specific antiarrhythmic drug (AAD) dosing. The software was developed to address disparities in AAD hospitalizations that disproportionately affect minority patients. We evaluated the usability of the software interface using the validated Post-Study System Usability Questionnaire (PSSUQ) and mobile Health App Usability Questionnaire (MAUQ).

Methods:
Ten medical providers, 16 clinic staff, and 16 patients tested the novel software interface for remote titration of Sotalol and Dofetilide medications, followed by the validated PSSUQ and MAUQ surveys. An observer also evaluated each step of the software for completion and noted any challenges.

Results:
Providers rated the software interface highly, with an overall mean PSSUQ of 6.9 ± 0.2 and MAUQ of 6.8 ± 0.2, and 100% strongly agree on information quality (PSSUQ questions 7-12). Clinic staff and patients provided the highest ratings for system usefulness, with an overall PSSUQ mean of 6.4 ± 1.2 and MAUQ mean of 6.0 ± 1.2, ease of app use and user satisfaction, mean of 6.3 ± 1.1 and 5.9 ± 1.3 respectively. Eighty percent of users found the system easy to use and were satisfied, with 76% rating the app as an acceptable way to receive healthcare services and felt comfortable communicating with their providers using the app.

Conclusion:
The novel automated software application, designed to improve access to antiarrhythmic drugs and reduce healthcare disparities, received high usability ratings, indicating feasibility for remote administration of antiarrhythmic drugs.
Abstract 18510: Implanting a Novel Active-Fixation Leadless Pacemaker: A Single Center Experience With the Aveir VR
Authors: Alexander Nebu , Ahmad Huzaifa , Basyal Binaya , Kabadi Rajiv , Tsimploulis Apostolos , Islam Malick , Thomaides Athanasios , Weintraub William S , Dolman Sarahfaye , Eldadah Zayd , Hadadi Cyrus
Published: December 2023

Background:
The new Aveir VR (Abbott Medical, CA) active-fixation leadless pacemaker (LP) is the second LP system to become available in the United States after the Micra (Medtronic, MN) and offers design improvements over its predecessor, the Nanostim. It uses a unique mapping capability to help reduce repositioning attempts prior to fixation and utilizes a helical fixation mechanism for implantation and chronic retrieval. We describe the current largest real world descriptive single center experience with the new Aveir VR LP.

Method:
We describe characteristics and outcomes of patients who underwent implantation with the single chamber Aveir VR between May 2022 and June 2023. Data was collected from electronic medical records, and procedural logs. Variables collected included demographics (eg age, sex, race), procedural characteristics (e.g., procedure length, fluoroscopic duration), hospital length of stay and time to discharge, pacing parameters and complications.

Results:
A total of 88 patients underwent implantation with the single chamber Aveir VR. The most common indications were symptomatic bradycardia due to sinus node dysfunction (50%), atrioventricular block (34%), and atrial fibrillation with bradycardia (12.5%). Average age was 73.4 years, 52.3% were male, and 53.4% were African Americans. The median procedure duration was 83 minutes (range 36 - 298) and median fluoroscopy time was 10.3 minutes (range 1.4-41.6). Procedure duration improved from a median of 97.5 minutes in the first 10 cases to a median time of 64.5 minutes in the last 10 cases. The average number of mapping locations was 1.7, implant location was RV Apical Septum in 92% of patients, and 0.1% of patients required repositioning. The average R wave amplitude at implant was 7.3 mV (range 2.5-18 mV), average impedance was 763 Ω (range 310-1800), and average pacing threshold was 0.99V (range 0.25-4.5) at 0.4ms. There were no periprocedural complications with any of the implantations. The median hospital length of stay was 5.75 days (range 0.25-77.5), with median time from implant to discharge in elective patients of 50.5 hours.

Conclusion:
Our experience demonstrates that implantation of the single chamber Aveir VR LP to be safe and effective, comparable to trial data.
Abstract 18515: Prevalence of Right and Left Atrium Non-Pulmonary Vein Triggers in Cardiac Amyloidosis Patients Undergoing Atrial Fibrillation Ablation
Authors: La Fazia Vincenzo Mirco , Pierucci Nicola , Gianni Carola , Mohanty Sanghamitra , Della Rocca Domenico G , Torlapati PremGeeta , Salagundla Nethuja , Bassiouny Mohamed , Gallinghouse G , Burkhardt John , Horton Rodney , Al-Ahmad Amin , Di Biase Luigi , Natale Andrea
Published: December 2023

Introduction:
Cardiac amyloidosis (CA) has been associated with an increased risk of atrial arrhythmias due to infiltration of the amyloid protein in the atrial wall. Though non-pulmonary vein(PV) triggers are commonly seen in left atrium, they are also seen in the right side of the heart, so identifying them at the time of ablation is essential. Minimal data exists on the prevalence of triggers in amyloidosis patients.

Aim:
The study evaluates the prevalence of non-PV triggers during catheter ablation in atrial fibrillation (AF) patients affected by cardiac amyloidosis

Methods:
This is a study including 74 consecutive patients with an established diagnosis of amyloidosis ATTR diagnosed with cardiac MRI or myocardial biopsy that underwent their first AF catheter ablation. They underwent PV isolation + isolation of left atrial posterior wall and superior vena cava. Additionally, extrapulmonary triggers, which are defined as ectopic triggers originating from sites other than PVs including left atrial appendage (LAA), coronary sinus (CS), interatrial septum, crista terminalis, mitral valve anulus were identified and ablation in all 74 patients. Post procedure, patients were followed up routinely with ECG during office visits, 7-day Holter monitor and event recorders for the duration of 1 year.

Results:
Isoproterenol-challenge revealed non-PV triggers in 51 (68.9%) patients. These triggers were mostly mapped to LAA (39, 52.7%), CS (30, 40,5%), and crista terminalis (35, 47.3%). Besides, ectopic beats were seen originating from inter-atrial septum (19, 25.6%), mitral valve annulus (10, 13.5%). More than one trigger was found in (68%) patients.At 1-year after the ablation, 65 (87.8%) were arrhythmia-free off AADs.

Conclusions:
Our findings suggest that non-PV triggers are highly prevalent in cardiac amyloidosis AF patients including a much higher rate crista terminalis firing compared to the standard population.
Abstract 18561: Trends Among Patients Undergoing Transvenous Lead Extraction: A Single Center Experience
Authors: Ayub Muhammad Talha , Mathew Don , Aronis Konstantinos , Kancharla Krishna , Bhonsale Aditya , Thoma Floyd W , Voigt Andrew , Jain Sandeep , Estes Nathan A , Saba Samir , Shalaby Alaa
Published: December 2023

Background:
In recent years there has been an increase in cardiac device-related infections and the need for transvenous lead extraction (TLE). Limited data exist on secular trends in baseline characteristics and outcome measures among patients undergoing this high-risk procedure.

Objective:
To examine secular trends in baseline characteristics and outcomes for patients undergoing lead extraction procedure at our institution.

Methods:
We conducted a retrospective chart review of patients undergoing TLE from 2010 to 2021, at a tertiary academic institution. Patients were divided into three epochs (2010-2013, 2014-2017 and 2018-2021). Baseline characteristics in hospital length of stay (LOS) and survival were compared between groups.

Results:
A total of 794 patients, with a mean age of 64±16 years, were analyzed. 481 (60%) patients had infection as the indication for TLE. On average, 2 ± 1 leads were extracted per patient. The longest lead dwell time was 6.5 ± 4.8 years. Significant progressive increase in baseline comorbidity over time is noted (Table 1). A concomitant increase in infection indication versus lead management was also noted. There was a significant increase in the median hospital LOS across epochs; 3.88 IQR (1.26-10.06) for epoch 1 vs 7.34 IQR (2.25-13.35) for epoch 2, vs 9.06 IQR (5.78-14.05) for epoch 3 (P < 0.0001). While there was no difference in long term survival curves (log rank p =0.4), between group analysis showed higher risk for 30 day [RR 2.24(1.08-4.66) p=0.0306] and 1 year mortality [RR 1.44 (1.004-2.05) p=0.0478] between epoch 3 vs epoch 1.

Conclusion:
Across epochs, the number of TLE procedures performed decreased while patient morbidity increased with a notable increase in infection indication for the procedure. This corresponded to a progressive increase in hospital LOS and an emergent signal toward increased near-term mortality.
Abstract 18592: Association of Lactation Duration With Blood Pressure Recovery at One Year Postpartum in Overweight and Obese Individuals With a Hypertensive Disorder of Pregnancy
Authors: Hart Renee , Catov Janet M , Hauspurg Alisse
Published: December 2023

Introduction:
Hypertensive disorders of pregnancy (HDP) are associated with an increased risk of maternal cardiovascular (CV) disease. Lactation is associated with favorable metabolic and CV profiles, but its impact on blood pressure (BP) recovery following a HDP is less clear.

Hypothesis:
Longer lactation duration is associated with lower systolic and diastolic BP throughout the first year postpartum (PP).

Methods:
We utilized data from a randomized clinical trial of overweight and obese individuals with a HDP diagnosis and no pre-pregnancy hypertension. BP was assessed in triplicate along with self-reported lactation status at enrollment (6 weeks to 6 months PP) and follow up (8-12 months PP). Hypertension was defined as ≥130/80 mmHg or the use of anti-hypertensive medications. PP BPs were also obtained daily using home BP monitoring for the first six weeks, then one week per month for the remainder of the first year PP. We compared demographic and cardiometabolic outcomes by lactation status at both study visits using two-sample t-tests and chi-squared tests. We utilized multivariable logistic regression models to assess the relationship of lactation with hypertension and repeated BP measurements were fit to mixed-effects linear regression models by lactation status to assess BP recovery.

Results:
Data from 129 individuals included 14,177 home BPs. Overall, 81% of participants initiated lactation and mean lactation duration was 5.8 ± 4.0 months PP. At follow up (10.9 ± 2.1 months PP), both systolic (p=0.004) and diastolic (p=0.008) BP were lower in individuals who lactated compared to those who did not. Each month of lactation was associated with a 12% (aOR 0.88; 95% CI 0.78-0.98) decreased odds of hypertension at one year PP with adjustment for age, race, education, BMI. Lactating individuals had a healthier BP recovery profile (p<0.01 for systolic and diastolic BP) in the first year PP.

Conclusions:
In overweight and obese individuals with a HDP, lactation is associated with a statistically and clinically significant reduction in systolic and diastolic BP at one-year PP. This study emphasizes the need to address barriers to lactation to improve long-term CV health.
Abstract 18598: Contributions of Alpha-Ketoglutarate Dependent Oncometabolism to HFpEF in Two Mouse Models
Authors: Kamiar Ali , Williams Monique , Condor Jose Manuel , Rasmussen Monica Anne , Alitter Qusai , Webster Keith A , Kazmierczak Katarzyna , Liang Jingsheng , Szczesna-Cordary Danuta , Shehadeh Lina A
Published: December 2023

Introduction:
Switching from fatty acid oxidation to less efficient but more expeditious glycolysis is associated with oncometabolism and more recently cardiac hypertrophy.

Hypothesis:
We hypothesized that such a switch drives HFpEF in two diverse mouse models.

Methods:
WT/129J mice at age 4-weeks were subjected to biweekly p407 i.p. injections and a single i.v. injection of AAV9-cTnT-LDLR. A separate group of injected mice were fed a diet supplemented with alpha-ketoglutarate (2% αKG) at onset. 4-week-old Alport mice received either αKG diet or normal chow. Glucose uptake was measured by whole-body PET-CT imaging of 18F-FDG in four groups: (1) untreated (n=5), (2) LDLR/P407 at 1, 2, 4, 7 and 8-week treatment (n=3-5), (3) LDLR/P407 + αKG mice at 4-week treatment (n=5), and (4) 9-12-week Alport mice (n=5). Echocardiography was performed on all the groups (n=4-17). Mechanical and energetic measurements on skinned cardiac pupillary muscles were performed on late-stage Alport , 8-week-treated LDLR/P407 , 4-week-treated LDR/P407 + αKG mice, and untreated controls (n=4-9). Survival of LDLR/P407, LDLR/P407/αKG and control groups (n=8-13) were recorded.

Results:
PET-CT scans showed increased cardiac glucose uptake in Alport (FC=3, p< 0.05) and LDLR/P407 mice at 1, 2, 4 (FC = 2, p<0.05), and 8 weeks (FC=3.2, p<0.001). αKG diet increased cardiac glucose uptake in LDLR/P407 at 4 weeks compared to normal chow (FC=2.15, p<0.05). Doppler and echocardiography showed worse diastolic dysfunction (E/E’) (FC = 1.8, P<.05) in LDLR/P407 αKG mice at 4-weeks versus control chow and reduced heart size (volume) (FC = 0.41, P<0.05) and worse diastolic dysfunction in Alport mice fed αKG diet. Alport hearts favored a DRX state (FC= 1.52, p <.0001) while 8-week-LDLR/P407 hearts favored SRX (FC=1.1, p< 0.05). The SRX state was exacerbated by αKG diet in 4-week-LDLR/P407 relative to normal chow. Life spans of LDLR/P407 mice fed αKG diet were significantly shortened (p<0.001).

Conclusions:
The results support roles for oncometabolism in promoting HF and sudden death in Alport and LDLR/P407 mice, effects that were exacerbated by an αKG diet, and possibly caused by enhanced hypertrophic growth. The results suggest an αKGDH and phenotype-dependent redistribution of myosin energetic states
Abstract 18607: Sex-specific Metabolites Associated With Incident Stroke, Incident Coronary Heart Disease, Hypertension, And Chronic Kidney Disease In The Regards Cohort
Authors: Couch Catharine , Ament Zsuzsanna , Patki Amit , Kijpaisalratana Naruchorn , Bhave Varun M , Jones Alana , Armstrong Nicole D , Cushman Mary , Kimberly W T , Irvin Marguerite M
Published: December 2023

Sex disparities continue to exist in cardiometabolic diseases. Metabolomic profiling offers the ability to gain insight into disease mechanisms. The purpose of the present analysis was to identify metabolites associated with sex and determine if sex-specific metabolites are associated with incident stoke, incident coronary heart disease (CHD), hypertension (HTN), and chronic kidney disease (CKD). Targeted metabolomics was conducted for 358 metabolites in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Weighted logistic regression models were used to test the association between sex and metabolites. Metabolites meeting the Bonferroni-corrected threshold were selected for replication in the Hypertension Genetic Epidemiology Network study. Cox proportional hazard models were used to calculate hazard ratios (HRs) per unit standard deviation (SD) of each replicated metabolite with incident stroke and incident CHD. Weighted logistic regression models were used to calculate odds ratios (ORs) per unit SD of each replicated metabolite with prevalent HTN and prevalent CKD. A total of 1,898 individuals were included in the analysis and 50.47% of the sample was male sex. The mean age was 68.40 ± 10.55 years and 43% of the sample was Black race. Sixteen metabolites were associated with sex, meeting the Bonferroni-adjusted p-value of 1.4 x 10
-4
. These included 8 lipids, 6 amino acids, 1 indole, and 1 quinoline. Of these 16 metabolites, none were associated with incident stroke or incident CHD. Kynurenic acid and leucine were associated with HTN in the base model adjusting for age, sex, and race (kynurenic acid: OR 1.45, 95% CI [1.19, 1.76], p=2.36 x 10
-4
; leucine: OR 1.41, 95% CI [1.14, 1.76], p=2.03 x 10
-3
). Indole-3-lactic acid and kynurenic acid were associated with CKD in the full model adjusting for age, sex, race, smoking, alcohol use, and BMI (indole-3-lactic acid: OR 3.83, 95% CI [2.77, 5.29], p=5.93 x 10
-16
; kynurenic acid: OR 6.63, 95% CI [4.67, 9.41], p=1.50 x 10
-25
). Our findings shed light on the sexual dimorphism of the metabolome and suggest that differences in biochemical pathways may contribute to sex disparities in cardiometabolic disease risk.
Abstract 18617: Concurrent Postural Orthostatic Tachycardia Syndrome (POTS) and Vasodepressor Syncope: A Unique Case in a Young Female
Authors: Hassan Mubariz , Grewal Niyati , Waldron Shervonne , Munawar Muhammad Mohsin
Published: December 2023

Introduction:
Rare coexistence of postural orthostatic tachycardia syndrome and vasodepressor disorder in young patient's syncope poses intriguing diagnostic and treatment challenges. We report a case in a healthy young female.

Case:
A 28-year-old female without prior medical history presented with dizziness, palpitations, and syncope. A tilt table test revealed a significant increase in heart rate upon tilting to 70 degrees, indicative of postural orthostatic tachycardia syndrome (POTS). Later, administration of nitroglycerin resulted in syncope, consistent with vasodepressor disorder. Intravenous fluids alleviated symptoms. The patient was diagnosed with coexisting POTS and vasodepressor syndrome, treated with ivabradine for POTS, and compression stockings for vasodepressor disorder. Follow-up visits showed symptom improvement.

Discussion:
Autonomic disorders presenting as syncope pose diagnostic and therapeutic challenges due to their varied etiologies. Postural orthostatic tachycardia syndrome (POTS) involves excessive heart rate elevation upon upright posture, while vasodepressor syndrome manifests as orthostatic hypotension. Their coexistence is uncommon. Tilt table testing aids in distinguishing between the two. Treatment focuses on addressing specific pathophysiological mechanisms. Ivabradine and beta blockers target excessive tachycardia in POTS, while hydration and compression stockings mitigate orthostatic hypotension. Refractory cases may benefit from midodrine. A tailored approach is crucial in managing these complex autonomic disorders.

Conclusion:
Rare coexistence of two autonomic dysfunction syndromes emphasizes the need for tailored treatment. Individualized interventions, guided by underlying pathophysiology, are crucial. Larger studies are required for validation and to optimize diagnostic and therapeutic approaches in patients with coexisting POTS and vasodepressor syndrome.