bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4143119: National Inpatient Mortality Trend of Mitral Valve Transcatheter Edge-to-Edge Repair in Patients With End-Stage Renal Disease on Dialysis
Authors: Abood Zaid , Allaqaband Suhail , Galazka Patrycja , Tunink Kirsten , Sokhal Balamrit , Hommeida Mohamed , Bajwa Tanvir , Jan M. Fuad
Published: November 2024

Background:
Mitral valve transcatheter edge-to-edge repair (M-TEER) is performed for high-risk patients with severe mitral regurgitation and multiple comorbidities. End-stage renal disease (ESRD) is one poor prognostic factor in M-TEER. However, real-life, large-scale data on inpatient mortality in ESRD patients undergoing M-TEER are lacking.

Methods:
The National Inpatient Sample from Jan 2015 to Dec 2020 was used to identify the study cohort using the International Classification of Diseases, 9th&10
th
Revisions, Clinical Modificatio
n.
The primary outcome was overall in-hospital mortality for patients with and without ESRD undergoing M-TEER. The secondary outcome was inpatient mortality trends in these groups. Univariate and multivariate logistic regressions (adjustment for age, race, Elixhauser comorbidity index score) were used.

Results:
We evaluated 44,845 patients who underwent M-TEER, of whom 2135 (4.7%) had ESRD on dialysis. The ESRD group was younger than the non-ESRD group (69.9 vs 76.4 years, P<.001), with a similar percentage of females (41.9% vs 45.4%, P=.151). Total procedure number increased significantly from 3184 to 11680 during the study period (Fig 1A). Overall mortality was significantly higher in ESRD patients (11.7% vs 1.5%, P<.001). Adjusted mortality in the ESRD group increased from 2.2% in 2015 to 12.9% in 2020 (P=.025), whereas the mortality rate remained relatively stable in non-ESRD patients (2.1% to 1.5%, P=.150) (Fig 1B). The ESRD group was associated with a higher incidence of immediate postoperative complications, which may have contributed to higher mortality (Table).

Conclusion:
Patients with ESRD on dialysis undergoing M-TEER had significantly higher mortality rates than non-ESRD patients. Despite younger age, mortality for ESRD patients rose substantially; it remained relatively stable for non-ESRD patients. These findings highlight the elevated risk and need for tailored management strategies for ESRD patients undergoing M-TEER.
Abstract 4143176: Association Between Frailty Testing through Gait Speed and Mortality in CRT Patients: Report for a Multidisciplinary CRT Clinic
Authors: Paul Aritra , Demian Joe , Varma Niraj , Finet J. Emanuel , Kochar Arshneel , Bader Feras , Wazni Oussama , Tang Wilson , Rickard John
Published: November 2024

Background:
Identifying predictors of mortality in CRT patients remains an active area of investigation.

Objective:
To establish a relationship between gait speed (GS) and mortality in heart failure patients with CRT.

Hypothesis:
Patients with slower gait speeds have worse survival rates after CRT implantation.

Methods:
This retrospective study included 504 patients who underwent CRT implantation at our institution between 2017-2022. All patients were followed up with a multidisciplinary team, including electrophysiology and heart failure physicians about 6 months after CRT implantation, where frailty was assessed. We used GS as a measure of frailty and divided patients into 2 groups: GS: <1 m/s (n=177) and ≥ 1 m/s (n=327). The primary endpoint was a composite of left ventricular assist device implantation, transplant, or death at 2 years post-CRT. Data was collected retrospectively from electronic medical records.

Results:
The study population was 65.7% male, with a mean age of 69.1 years, with majority of the devices being CRT-D (79.6%). Response was defined as an improvement in LVEF >5% with reduction in LVESV>10%; anybody not meeting this definition was classified as a non-responder. Responder and non-responder rates among GS< 1 m/s and GS
>
1 m/s were 53.8% vs 66.4%; and 35.1% vs 26.2%, respectively. The median (IQR) GS was 1.15 m/s (0.91-1.37 m/s). 52 (10.3%) patients had a composite outcome within 2 years follow up. Non-parametric univariate analysis revealed that lower GS was significantly associated higher composite outcome rates (median GS 0.8 vs 1.18 m/s; p<0.001). Multivariate cox regression also revealed GS<1 m/s to be an independent predictor of our composite outcome [HR- 4.33 (2.20-8.86); p<0.001] (Table 1), with survival graphs showing patients with GS<1m/s having worse 2-year survival (Figure 1).

Conclusion:
Frailty testing using GS post-CRT implantation is a strong predictor of mortality in CRT patients.
Abstract 4143194: Clinical predictors of right ventricular contractile depression among patients with pulmonary hypertension
Authors: Kim Yoo Jin , Cubero Salazar Ilton , Jani Vivek , Hassoun Paul , Tedford Ryan , Hsu Steven
Published: November 2024

Background:
Right ventricular (RV) dysfunction in patients with pulmonary hypertension (PH) leads to drastically worse clinical outcomes. It remains difficult to find the best clinical correlates of intrinsic RV contractile dysfunction given the load dependent nature of these measures. Here, we evaluate which clinical indices may identify poor RV myocyte contractility among PH patients.

Methods:
Single-center cohort study of 14 patients with PH (10 with group 1 pulmonary arterial hypertension, 4 with group 2 secondary to heart failure). Clinical evaluation included transthoracic echocardiogram and RV pressure-volume loops measured at rest and during supine bike exercise. Myocyte mechanics were measured using frozen, permeabilized RV myocardium samples. Poor RV myocyte contractility was defined as >2 standard deviations below the mean of normal controls.

Results:
Among 14 PH subjects, we identified 6 and 8 patients with normal and depressed RV myocyte function, respectively. By area under the receiver operator curve (AUROC) analysis, we found that common clinical measures did not capture those with reduced RV myocyte contractile function: TAPSE (AUROC 0.70,
P-
value 0.26), RAP (AUROC 0.58,
P-
value 0.61), RAP/PCWP (AUROC 0.50,
P-
value >0.99), and PAPi (AUROC 0.52,
P
-value 0.90) (Figure 1A). We next investigated more sensitive methods of detecting RV dysfunction, such as RV contractile reserve measured during exercise. Changes in RV contractility and RV dilation during exercise were worse in those with poor RV myocyte contractility (Figure 1B). Using AUROC analysis, these measures of RV contractile reserve post-exercise were better able to identify those with intrinsic poor RV myocyte contractility: RV contractile reserve (AUROC 0.94,
P
-value <0.01) and RV exercise dilation (AUROC 0.85,
P
-value 0.03) (Figure 1C).

Conclusion:
Measures of RV contractile reserve are better than commonly obtained clinical measures of resting RV dysfunction at identifying underlying RV myocyte contractile weakness.
Abstract 4143207: Time in Target Mean Arterial Pressure Range and Mortality in HeartMate 3 LVAD Recipients
Authors: Delfiner Matthew , Miller Jason , Snider Jeffrey , Genuardi Michael , Ortega-Legaspi Juan , Prenner Stuart , Sidhu Kiran , Vidula Himabindu
Published: November 2024

Background:
The HeartMate 3 Device (HM3) is an afterload-sensitive left ventricular assist device (LVAD). International guidelines suggest a target Doppler blood pressure (BP) range between 70-90 mmHg, though this recommendation is supported mostly by expert consensus. Optimal real-world data remains lacking regarding the ideal BP for these patients. Remote patient monitoring (RPM) can be utilized for outpatient Doppler blood pressure monitoring. We aimed to evaluate the association between time spent in goal BP range and mortality in HM3 LVAD recipients.

Methods:
1,427 HM3 LVAD recipients from 74 centers using the ActiCare Health RPM system, which allows patients to measure Doppler BP and upload results to their care team, were included in this analysis. Inclusion criteria included patients with at least two BP measurements. Outpatient Doppler BP values were collected, and a standard therapeutic range (70–90 mmHg) was established. The percentage of time in the therapeutic range (TTR) was calculated, categorizing patients as ≥75%, 50-75%, and ≤50%. Survival at 600 days on LVAD support and reporting frequencies were compared between groups.

Results:
We studied 738 HM3 LVAD recipients, implanted from 2015 to 2024, with a mean duration of 715 ± 19 days on LVAD support. 140 (19%) patients died. A total of 144,562 Doppler BP readings were analyzed, with a mean value of 82.8 ± 0.02 mmHg. There were 481 patients with TTR ≥75% (65%), 138 patients with TTR 50-75% (19%), and 119 patients with TTR ≤50% (16%). There was a significantly greater probability of survival for those with TTR ≥75% compared to ≤50% (94% vs. 85% at 400 days and 88% vs. 84% at 600 days, p = 0.05, Figure). The mean number of BP submissions per 100 days for the ≥75% group was 37.8 ± 0.87, compared to 25.8 ± 0.87 in the 50-75% group and 21.7 ± 1.25 in the ≤50% group (p < 0.001).

Discussion:
The data suggest that HM3 patients who spend more than 75% of the time with a Doppler BP between 70-90 mmHg have greater survival compared to those who are within range less than 50% of the time. RPM can be used for closer monitoring of Doppler BP in HM3 LVAD recipients. Patients with Doppler BP 70-90 mmHg may have improved survival.
Abstract 4143306: Circulating Factors in Single-Ventricle Congenital Heart Disease Promote Pathological Metabolic Remodeling in Cardiac Myocytes, Which is Abrogated with Phosphodiesterase-5 Inhibitor Therapy
Authors: Pietra Ashley , Turner Mary , Sparagna Genevieve , Stauffer Brian , Sucharov Carmen , Miyamoto Shelley , Garcia Anastacia
Published: November 2024

Introduction:
While operative and perioperative care continues to improve for single ventricle heart disease (SVHF), the 10-year survival in this population is only 39-50%. Phosphodiesterase-5 inhibitors (PDE5i) are increasingly used in this population, however there are currently no proven medical therapies for SVHF. Our group has previously demonstrated that SVHF myocardium is characterized by increased PDE5 activity and impaired mitochondrial bioenergetics, however little is known regarding myocardial effects of PDE5i therapy. We hypothesize SVHF serum circulating factors are distinct from healthy controls and contribute to cardiomyocyte metabolic dysfunction, thereby promoting heart failure progression. Additionally, we hypothesize that PDE5i abrogates these pathologic metabolic alterations.

Methods:
Mass spectrometry-based proteomics and metabolomics were performed on healthy control and SVHF patient sera. Using an established novel
in vitro
model, primary cardiomyocytes (neonatal rat ventricular myocytes, NRVMs) were treated with serum +/- 1.5µM PDE5i for 72 hours. In NRVMs, the Seahorse Bioanalyzer was used to assess mitochondrial bioenergetics and mass-spectrometry was used to assess lipid and metabolite profiles.

Results:
Unbiased proteomic and metabolomic analysis suggests the serum circulating peptide and metabolite milieu in SVHF is significantly altered, including significant dysregulation of pathways involved in mitochondrial metabolism, glycolysis, amino acid metabolism, oxidative stress, and inflammation (Panel 1). Additionally, SVHF serum circulating factors pathologically remodel cardiomyocytes, including decreased cardiolipin and phosphatidylglycerol lipid species, and shifted metabolite profiles suggesting altered glycolysis, CoA biosynthesis, oxidative phosphorylation, and fatty-acid beta-oxidation (Panel 2). Importantly, PDE5i treatment abrogates the SVHF serum-induced changes in phosphatidylglycerol, and in various metabolites, including in glucose-6-phosphate, pyruvate, and L-carnitine (Panel 3).

Conclusions:
Together, these data suggest PDE5i therapy has direct myocardial effects, and likely contributes to beneficial cardiomyocyte metabolic remodeling in SVHF.
Abstract 4143311: Non-statin Medication Utilization under Medicare Part D Population
Authors: Parajuli Shreyash , Majmundar Vidit , Pandey Priya , Joshi Amir , Yamparala Aishwarya , Dani Sourbha
Published: November 2024

Introduction:
Statin intolerance is reported in 5–30% of patients and contributes to reduced statin adherence and persistence, as well as a higher risk for adverse cardiovascular outcomes. For patients with known or suspected statin intolerance and high ASCVD risk, non-statin therapy is currently a class IIa recommendation by the National Lipid Association (NLA).

Method:
We accessed publicly available datasets from the Centers for Medicare and Medicaid Services (CMS). The non-statin medications included in these studies are bempedoic acid, evolocumab, alirocumab, inclisiran, and evanicumab. Key variables, such as beneficiaries, claims, and total spending, were analyzed and presented below. We looked at the trend of medication from 2020 to 2022. All costs were adjusted for inflation and represented in 2022 US dollars.

Results:
We analyzed CMS Medicare Part D plans of Bempedoic Acid, Inclisiran, Alirocumab, Evolocumab and Evanicumab, covering 2020–2022. We noticed a 3- to 4-fold increase in total beneficiaries and claims for bempedoic acid, along with a sharp rise in total spending from 3.5 million dollars to 19.4 million dollars after adjusting for inflation rate using the consumer price index inflation calculator. The trends for other non-statin medications were similar. We also created comparative graphs for 2022 and noticed a total spending of 97.5% among proprotein convertase subtilisin/kexin type 9 (PCSK-9) in Medicare D CMS populations.

Discussion
We can see a rise in total Medicare spending among all the drugs. Amongst different lipid-lowering agents, proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are the most commonly used, followed by bempedoic acid. Newer agents, like Evanicumab and Inclisiran are also available on the market, and their trend has not yet been determined. Inclisiran, however, has the highest average spending per beneficiary. How the Inflation Reduction Act of 2022 will affect drug utilization is yet to be seen.

Limitation
The pattern of data used may not be generalizable to other payer demographics. Policy changes can affect the comparability of data over different periods.

Conclusion

From 2020 to 2022, the number of claims, beneficiaries, and total spending on various lipid-lowering agents steadily increased.
Abstract 4143321: Platelets induce endothelial cell mitochondrial dysfunction in myocardial infarction
Authors: Sun Haoyu , Schlamp Florencia , Liberow Sarah , Smilowitz Nathaniel , Hochman Judith , Reynolds Harmony , Barrett Tessa , Berger Jeffrey
Published: November 2024

Background:
Coronary endothelial dysfunction plays a key role in the pathogenesis of cardiovascular events. In the setting of myocardial infarction (MI), activated platelets release prothrombotic and proinflammatory factors, contributing to vascular injury and dysfunction. However, the effect of platelets on coronary endothelial function during MI is not fully understood. We investigated the effect of platelets from patients with MI on cultured coronary endothelial cells in vitro.

Methods:
Platelet RNA sequencing was performed and platelet releasates were obtained from patients with acute MI (n = 24) and control patients with stable coronary artery diseases (n = 22) who were referred to invasive coronary angiography. Human coronary artery endothelial cells (HCAECs) were treated with platelet releasates for 6 hours and collected for RNA sequencing. Mitochondrial function of treated HCAECs was evaluated by live cell imaging and JC-1 assay with flow cytometry.

Results:
Overall, 1832 genes were differentially expressed in the transcriptome of HCAECs treated with MI (vs control) platelets (p < 0.05). Ingenuity pathway analysis found that mitochondrial dysfunction (up-regulated; p = 1.7 × 10
-8
) and oxidative phosphorylation (down-regulated; p = 7.2 × 10
-8
) were the top two altered pathways in HCAECs treated with MI platelets (
Figure A&B
). Consistently, live cell imaging with MitoTracker Red staining and JC-1 assay by flow cytometry showed MI (vs. control) platelet releasate-treated HCAECs had reduced mitochondrial membrane potential. By correlating the differentially expressed platelet genes in MI vs controls, we identified the platelet gene cluster that induced endothelial cell mitochondrial dysfunction, which was enriched in coagulation, platelet activation, and platelet degranulation (
Figure C
).

Conclusions:
Platelets-derived mediators from patients with MI induce altered endothelial cell gene expression and mitochondrial dysfunction.
Abstract 4143329: Moderate renal dysfunction is independently associated with increased risk of sudden cardiac arrest but only in males
Authors: Truyen Thien Tan Tri Tai , Uy-Evanado Audrey , Chugh Harpriya , Reinier Kyndaron , Charytan David , Chugh Sumeet
Published: November 2024

Introduction:
Moderate renal dysfunction is independently associated with increased cardiovascular mortality. Sudden cardiac arrest (SCA) accounts for at least 25% of chronic kidney disease (CKD) mortality. However, there is a lack of population based studies evaluating a potential association between moderate CKD and SCA.

Hypothesis:
Moderate CKD is associated with SCA in the general population.

Methods:
We conducted a case-control study from an ongoing, prospective community-based study of SCA in the US Northwest (catchment population ~1 million; 2002-2020). Cases were individuals who suffered SCA aged 40 to 85 years, who had detailed medical records available, and serum creatinine levels measured before their SCA event. Control participants had no history of SCA and were recruited from the same geographical area. Cases and controls were frequency-matched by age and sex in a 3:1 ratio. Moderate CKD was defined as eGFR 30 to <60 mL/min/1.73 m
2
using the CKD-EPI 2021 formula.

Results:
We compared 2729 SCA cases and 1097 controls, with mean ages of 65.9 and 66.4 years, and male percentages of 68.6% and 66.1%, respectively. SCA cases had higher proportion of moderate CKD (22.8 vs. 18.0%, p=0.001) and lower eGFR (69.3 [44.8-89.7] vs. 77.6 [63.6-90.7] mL/min/1.73 m
2
, p<0.001) than controls. Multivariable regression analysis adjusted for demographics (age, sex, race) and comorbidities showed that both moderate and severe CKD were independent risk factors for SCA with an odds ratio (OR) of 1.43 (95% confidence interval (CI) 1.16-1.76) and 4.94 (95% CI 3.29-7.39), respectively. Moderate CKD was associated with SCA in male (OR 1.65, 9% CI 1.26-2.166) but not female individuals (OR 1.11, 95%CI 0.78-1.57) whereas SCA risk was similarly increased for men and women with more severe CKD. These findings were consistent across different high-risk populations (Figure).

Conclusion:
Both moderate and severe CKD are associated with SCA in the general population, but females with moderate CKD appear to be protected. These findings of possible renal involvement in SCA, even during early stages of CKD, warrant further investigation.
Abstract 4143371: Lactosylceramides Impair Cardiac Myocyte Function in HLHS
Authors: Ramaswamy Praveen , Turner Mary , Pietra Ashley , Garcia Anastacia
Published: November 2024

Introduction:
Hypoplastic left heart syndrome (HLHS) is a cardiovascular malformation that is a leading cause of cardiovascular related infant mortality. The cause of HLHS and the progression of heart failure (HF) in this population remains unclear. Additionally, there are no current medical therapies for the treatment of prevention of HF in HLHS. Our data suggests that the glycosphingolipid lactosylceramide (LacCer) is elevated in the heart of HLHS infants when compared to healthy age-matched controls. Based on this we hypothesize that elevated levels of LacCer contributes to cardiomyocyte dysfunction in HLHS.

METHODS:
To test the effect of LacCer on myocytes directly, neonatal rat ventricular myocytes (NRVMs) were isolated and treated with liposomes containing 3µM LacCer (C18:0 and C24:0) or vehicle. Global cardiomyocyte proteomics changes were analyzed via mass spectrometry (n=11 for vehicle, n=13 for LacCer). The mitochondrial uptake of long chain fatty acids was examined using a stable-isotope based carnitine palmitoyltransferase (CPT) activity assay (n=4 for vehicle, n=3 for LacCer). Mitochondrial bioenergetics, including fatty acid oxidation +/- etomoxir (CPT inhibitor), were assessed using an Agilent Seahorse Bioanalyzer (n=5 for each treatment).

RESULTS:
Our proteomics data identified 188 significantly differentially regulated proteins in response to LacCer treatment, with a significant number of proteins involved in glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, and muscle contraction (Fig A). Additionally, Lacer treatment was also sufficient to impair mitochondrial CPT activity, which is required for the uptake of long-chain fatty acids. Correspondingly, LacCer treatment significantly impaired fatty acid oxidation, illustrated by significantly decreased maximal mitochondrial respiration and energetic reserve capacity (Fig B -C).

CONCLUSIONS:
Together, these data demonstrate the potential role of LacCer in the pathophysiological remodeling of HLHS cardiomyocyte metabolic function and substrate utilization. Moreover, it also indicates LacCer as a potential target of therapy to halt or delay heart failure progression in HLHS patients.
Abstract 4143441: Variation in Hypertensive Blood Pressure and Association with Body Mass Index in a Disaggregated Population of Asian and Pacific Islander Adolescents
Authors: Njuguna Veronica , Zhang Sherry , Darbinian Jeanne , Ramalingam Nirmala , Naderi Sahar , Shin Edward , Lo Joan
Published: November 2024

INTRODUCTION
In the United States, 3 million children have hypertension (HTN), a cardiovascular disease (CVD) risk factor. However, blood pressure (BP) findings in specific Asian ethnic populations remain understudied. This study examines the prevalence of HTN-range BP among subgroups of Asian and Pacific Islander (API) adolescents.

Methods:
In a cohort of 88,145 API adolescents aged 13-17y with a well child visit in 2013-2019, systolic and diastolic BP and body mass index (BMI) were examined. Those with underweight BMI were excluded. The prevalence of BP ≥130/80 (HTN-range BP) was examined by API ethnicity. Covariates included age, sex, BMI category, and neighborhood deprivation index (NDI). Multivariable logistic regression examined the association of API ethnicity with HTN-range BP, providing adjusted odds ratios (OR) with [95% confidence intervals].

Results:
The cohort included 11,694 Chinese, 17,279 Filipino, 5,342 South Asian, 3,495 Southeast Asian, 4,051 Native Hawaiian/Pacific Islander (NHPI) and 46,284 of other/unknown API ethnicity. Mean age was 14.3±1.4y; 50% were female. Prevalence of HTN-range BP was highest for NHPI (11.8%) followed by Filipino (9.6%), and lowest for Southeast Asian (7.0%), Chinese (7.1%), and South Asian (7.6%) adolescents. The proportion with obesity also varied, ranging from 6.5% (Chinese) to 11.3% (South Asian), 12.1% (Southeast Asian), 17.7% (Filipino) and 29.5% (NHPI). Accounting for age, sex, and NDI quartile (Chinese as reference), NHPI (OR 1.54 [1.36-1.74]) and Filipino (OR 1.27 [1.16-1.39]) adolescents had higher odds of HTN-range BP while South Asian (OR 1.10 [0.97-1.24]) and Southeast Asian (OR 0.92 (0.79-1.07]) did not. After adjusting for BMI, the odds of HTN-range BP did not differ for NHPI (OR 1.03 [0.90-1.16]) and Filipino (OR 1.04 [0.95-1.14]) vs Chinese adolescents, but Southeast Asian adolescents had lower odds (OR 0.84 [0.72-0.98]). Sex (OR 1.7 [1.6-1.8]) and BMI (OR ranged from 1.9 [1.8-2.1] to 5.8 [5.3-6.3] in adolescents with overweight and severe obesity) were strongly associated with HTN-range BP.

DISCUSSION
The higher odds of HTN-range BP among Filipino and NHPI compared Chinese adolescents were largely attributable to higher BMI, suggesting that BMI may be an important factor in elevated BP among these high-risk Asian subgroups during adolescence. Efforts focused on pediatric obesity management, including lifestyle intervention, may be integral to reducing HTN and CVD risk prior to adulthood.
Abstract 4143445: Regardless of age or gender, diet quality, smoking status, and, exercise are key to cardiovascular health
Authors: Huang Tsuey-yuan , Tsai Ming-Fen , Moser Debra
Published: November 2024

Introduction:
Maintaining a heart-healthy lifestyle is crucial for good cardiovascular health. However, the moderating effects of age and gender on the relationship of diet quality, smoking status, and exercise to cardiovascular health are unknown. The purpose of this proposed study was to investigate the moderating effects of age and gender on the relationship of diet quality, smoking status, and exercise to cardiovascular health in community-dwelling adults in Taiwan.

Methods:
Cardiovascular health was defined using American Heart Association Life’s Simple 7 (LS7) scores, including cholesterol levels, blood pressure, blood sugar, body mass index, diet, smoking status, and physical activity levels, that were collected using a self-administered questionnaire and blood tests. Healthy lifestyle (diet quality, not smoking, and exercise) was also defined using a self-administered questionnaire. PROCESS macro model 3 was used to analyze the moderation effects of age between genders, the continuous independent variable (X) healthy lifestyle, the continuous dependent variable (Y) LS7, the categorical moderator (W) gender, and the continuous moderator (Z) age.

Results:
We recruited 484 participants (35.33±23.39 yrs., 86% female). The final model was significant (R2=51.19%, F=125.49, p=.000). Healthy lifestyle is a predictor of cardiovascular health (β=1.14, p=.000). However, the regression coefficient for XMW is not statistically significant, b7=0.0018, F (476) =0.1131, p=.7368, meaning that there is no three-way interaction between healthy lifestyle, age, and gender.

Conclusion:
The study findings elucidate that while gender and age can impact the prevalence rates of cardiovascular diseases, the effect of adopting a healthy lifestyle on cardiovascular health remains consistent across different age groups and genders. Consequently, regardless of age or gender, fostering a cardioprotective lifestyle is paramount.
Abstract 4143450: Strong correlation between preoperative CT-reconstructions and postoperative samples in the assessment of mitral annular calcification: Validation of Calcium scores and MAC scores
Authors: Kang Jagdip , Luppi Andre , Bielichenko Svitlana , Borger Michael , Sundt Thoralf , Ghoshhajra Brian , Melnitchouk Serguei
Published: November 2024

Background:
The surgical management of severe mitral annular calcification (MAC) has become an increasingly common challenge. Accurate preoperative prediction of the extent and location of calcification is crucial for preoperative planning, informed consent, and safe surgical management.

Hypothesis:
CT-derived calcium scores correlate with the Guerrero classification of MAC severity. Furthermore, CT reconstructions provide an accurate representation of calcifications observed in postoperative macroscopic specimens.

Methods:
Patients with preoperative CT imaging and MAC resection were included. Preoperative CT assessed MAC using Aquarius, TeraRecon software (V.4.7). Severity was graded based on calcium thickness, distribution, and involvement of leaflets and trigones according to the Guerrero classification. Calcium scores were quantified using the Agatston method, and MAC was 3D reconstructed. The relationship between calcium and MAC scores was assessed using Spearman's ρ. Additionally, qualitative comparisons were made between CT reconstructions and postoperative samples.

Results:
A total of 31 patients were analyzed, with a median age of 74. Two patients had mild MAC (mean calcium score: 2996), 14 had moderate MAC (mean calcium score: 6105), and 15 had severe MAC (mean calcium score: 9271). There was a strong positive correlation between preoperative calcium scores and Guerrero classification grades (Spearman's ρ = 0.65, p < 0.01). Qualitative assessment showed a high degree of similarity between preoperative CT reconstructions and postoperative macroscopic findings.

Conclusions:
The study demonstrates a strong correlation between preoperative CT-derived calcium scores and the Guerrero classification of MAC severity. However, the high degree of similarity between preoperative CT reconstructions and postoperative samples carries a higher informational value than the MAC score itself. Preoperative CT reconstructions of MAC, coupled with the calcium score as a surrogate for MAC volume and severity, provide the most accurate assessment of MAC for surgical planning and evaluation of alternatives. Further studies are required to determine preoperative criteria that predict safe MAC resections.
Abstract 4143464: Comparison of The Burden of Cardiovascular-Kidney-Metabolic Syndrome Components in Heart Failure with Preserved Ejection Fraction clinical trials and Heart Failure in the General United States Population
Authors: Hammond Michael , Cyrille-Superville Nicole , Givertz Michael , Desai Akshay , Redfield Margaret , Chirinos Julio , Kitzman Dalane , Bertoni Alain , Borlaug Barry , Lewis Gregory , Sharma Kavita , Lopez Javier , Shah Sanjiv , Khan Sadiya , Rasmussen-Torvik Laura
Published: November 2024

Introduction:
Patients with heart failure with preserved ejection fraction (HFpEF) have a high burden of comorbidities. To recognize the complex interplay of obesity, diabetes, and chronic kidney disease (CKD) in patients with cardiovascular disease, the cardiovascular-kidney-metabolic (CKM) syndrome was recently defined, but data on the burden of CKM in HFpEF is limited.

Aim:
We sought to describe the prevalence of CKM components in HFpEF leveraging data from control participants in clinical trials and NHANES.

Methods:
We analyzed data presented in publications from four randomized clinical trials that enrolled participants with HFpEF (all of which are available via NHLBI BioLINCC and will be included in the extant HeartShare dataset): TOPCAT, RELAX, NEAT-HFpEF, and INDIE. We abstracted baseline demographic and clinical variables from study publications to define CKM components (e.g., body mass index [BMI], diabetes status, hypertension, CKD status). We compared prevalence of CKM in these trials with a representative sample of US adults with self-reported history of heart failure (HF) from NHANES 2011-2018.

Results:
We included 1937 patients with HFpEF from four trials with enrollment between 2006-2016 and 715 adults representing 5.6 million adults aged ≥40 years with a self-report of HF between 2011-2018 from NHANES (
Table
). Mean age was similar among enrolled trial participants with HFpEF and those with HF in NHANES (~68-69 years). Mean BMI was in the obesity range and was similar among trial participants with HFpEF and HF in NHANES (31-35 kg/m
2
). A significant proportion of individuals had hypertension in HFpEF trials (>80%) and in the NHANES sample with HF (89%). The proportion of stage ≥ 3 CKD in HFpEF trials (≥ 37%) was similar to the NHANES sample with HF (37%). Results are shown in
Table
.

Conclusions:
Patients with HFpEF enrolled in clinical trials and those with HF in general population are significantly enriched with CKM components that may contribute to morbidity and mortality. Similar prevalence estimates were observed despite variability in trial inclusion criteria and heterogeneity in defining HFpEF and highlight CKM as a central target for HFpEF management.
Abstract 4143475: Early Dementia Prediction Using Electrocardiogram: Insights from Variational Autoencoder-Derived Features
Authors: Kim Yujeong , Park Yu Rang , Kim Woo Jung , Yoon Dukyong
Published: November 2024

Introduction:
Dementia, characterized by cognitive decline and impaired judgment, imposes a significant economic burden due to its rising prevalence and high diagnostic costs. Recent research has linked dementia to various biomarkers, including cardiac biomarkers like heart rate variability. This study investigates the use of Variational Autoencoder (VAE)-derived features from electrocardiogram (ECG) data for predicting dementia, offering a cost-effective alternative to traditional diagnostics.

Hypothesis:
Features derived from VAE applied to ECG data can be utilized to predict dementia.

Methods:
ECG data from Sinchon and Yongin Severance Hospital, South Korea, were used to develop a VAE-based predictive model. Patients diagnosed with dementia and matched controls without dementia were included, using propensity score matching for age and gender. For the dementia-develop group, data from the 5 years preceding the first diagnosis were used; for the dementia-free group, the ECG date at the median age served as the index date. Each median ECG was processed through the VAE to derive 32 features. A Deep Neural Network (DNN) was used to predict dementia 5 years before the index date, with Sinchon data for training and Yongin data for testing. Trajectory analysis of VAE features revealed distinct trends between the groups.

Results:
The model achieved AUROCs of 0.749 (training) and 0.701 (testing), and AUPRCs of 0.490 (training) and 0.358 (testing). Further analysis of VAE-derived feature trajectories showed significant temporal patterns. ECG markers that increased markedly in the dementia-develop group as the index date approached were associated with QT interval differences and T-wave morphology variations. Conversely, markers that increased in the dementia-free group but decreased in the dementia-develop group were linked to ST wave differences and amplitude disparities (Figure1). These findings underscore the potential of VAE-derived ECG features to distinguish between dementia-develop and dementia-free individuals over time.

Conclusion:
The model using VAE-derived ECG features highlighted the potential of combining ECG data with advanced machine learning techniques for early dementia screening.
Abstract 4143487: Refining Risk Prediction in Systemic Sclerosis Pulmonary Arterial Hypertension
Authors: Osgueritchian Ryan , Mombeini Hoda , Jani Vivek , Gami Abhishek , Hsu Steven , Hummers Laura , Wigley Fredrick , Lammi Matthew , Hassoun Paul , Shah Ami , Mathai Stephen , Mukherjee Monica
Published: November 2024

Background:
Given the high morbidity and mortality of pulmonary arterial hypertension (PAH), several risk stratification tools have been developed to enhance patient prognostication and management. PAH commonly complicates patients with systemic sclerosis (SSc). However, the disease-specific performance of these scores is unknown.

Research Question:
To determine the prognostic value of clinical PAH risk scores in SSc and further determine if echocardiographic coupling metrics improve risk score performance.

Methods:
We included a well-characterized cohort of SSc-PAH patients from Johns Hopkins Medicine with echocardiograms within six months of invasive confirmation of PAH status. Conventional and speckle-tracking echocardiographic analysis was performed. Four scores were calculated: COMPERA 2 4-Risk Strata, REVEAL 2.0, REVEAL Lite 2, and French Criteria. Cox regression with the corresponding C-statistic was used to assess each hazard ratio and predictive power. A new model incorporating coupling parameters with the risk score was generated and compared to the original risk model with Likelihood Ratio (LR) tests.

Results:
Our cohort consisted of 174 SSc-PAH patients, 63.6 ± 12.7 years, 85.6% female, and 76.4% White, 86% limited SSc, with moderate-severe SSc-PAH on average.
Table 1
. Across risk scores, C-statistics ranged from 0.63-0.69 in SSc-PAH,
Table 2
. The incorporation of RVGLS/PASP, RVFWS/PASP, and mid-RVFWS/PASP to each risk score model significantly improved mortality prediction (LR test p-value<0.05) with RVGLS/PASP providing the greatest difference in C-statistic across all models.

Conclusion:
Established risk scores have a modest predictive capacity for mortality in SSc-PAH. Incorporating echocardiographic parameters of right ventricular to pulmonary arterial coupling enhances the performance of these risk scores, aiding in the prognostication of mortality.
Abstract 4143504: Genetically Prolonged Beige Fat In Male Mice Confers Long-lasting Metabolic Health
Authors: QIAN YANYU , Wu Ruifan , Park Jooman , Jiang Yuwei
Published: November 2024

Background:
Beige adipocytes, express UCP1 and have thermogenic capability, making them a promising target for obesity treatments. However, beige adipocytes quickly transition into white adipocytes upon removal of stimuli. Our research identifies the cyclin-dependent kinase inhibitor 2A (
Cdkn2a
) as a crucial regulator of this transition. Ablation of
Cdkn2a
prolongs beige adipocyte lifespan, enhances energy expenditure, and improves glucose tolerance by inhibiting BECN1-mediated autophagy. These findings offer a potential therapeutic strategy to maintain beige adipocytes and combat obesity and related diseases.

Methods:
We used Ucp1-Cre
ERT2
mice with a Rosa26R
RFP
indelible labeling reporter and
Cdkn2a
floxed mice. All mice were maintained on a mixed C57BL6/J-129SV background. To induce Cre recombination, mice received tamoxifen for 2 days. For in vitro induction, cells were treated with 2 µM 4-hydroxy-tamoxifen. In our in vitro study, we isolated stromal vascular fraction (SVF) cells from the inguinal white adipose tissue (IGW) or brown adipose tissue (BAT) of 6-week-old male mice for seeding. For the in vivo study, we used cold exposure, metabolic cages, and glucose tolerance tests.

Results:
Cdkn2a
plays a pivotal role in the beige-to-white transition. Its absence prolongs the lifespan of beige adipocytes and in male mice, confers long-term metabolic protection against diet-induced obesity, along with enhanced energy expenditure and improved glucose tolerance. Mechanistically,
Cdkn2a
promotes the expression and activity of beclin 1 (BECN1) by directly binding to its mRNA and its negative regulator BCL2 like 1 (BCL2L1), activating autophagy and accelerating the beige-to-white transition. Reactivating autophagy by pharmacological or genetic methods abolishes beige adipocyte maintenance induced by
Cdkn2a
ablation. Furthermore, hyperactive BECN1 alone accelerates the beige-to-white transition in mice and human. Hence, blocking
Cdkn2a
-mediated BECN1 activity holds therapeutic potential in treating obesity and related metabolic diseases.

Conclusion:
Cdkn2a
depletion extends beige adipocyte lifespan, providing long-term metabolic benefits against diet-induced obesity in male mice.
Cdkn2a
boosts BECN1 expression, triggering the beige-to-white transition by directly interacting with BECN1 mRNA and its negative regulator BCL2L1, activating autophagy. Targeting
Cdkn2a
-mediated BECN1 activity holds promise as a therapeutic approach for treating obesity.
Abstract 4143513: ECG-AI to Assist with the Classification of Low Ejection Fraction and Heart Failure with Preserved Ejection Fraction
Authors: Karabayir Ibrahim , Davis Robert , Tootooni M. Samie , Chinthala Lokesh , Soliman Elsayed , Jefferies John , Baykaner Tina , Shah Sanjiv , Bertoni Alain , Kitzman Dalane , Herrington David , Akbilgic Oguz
Published: November 2024

Background:
There are delays on identification of people with low left ventricular ejection fraction (LVEF) and Heart Failure with preserved EF (HFpEF). There is a need for low cost and accessible tools to identify individuals who can benefit from more comprehensive exams such as echocardiogram (ECHO).

Research Goal
To develop electrocardiographic artificial intelligence (ECG-AI) models that can classify low EF and HFpEF.

Methods:
We developed an ECG-AI model using convolutional neural networks to classify 12-lead ECG’s into four categories: rEF( LVEF<40), mEF (40≤LVEF<50), HFpEF (clinical HF diagnosis with EF≥50) and controls with no HF diagnosis within 5-years of the index ECG. For rEF, mEF, and HFpEF categories, ECHO were used to determine LVEF. Patients with clinical HF diagnosis without ECHO data were excluded. In patients with ECHO, only available ECGs within 30-days of the ECHO study was utilized. The ECG-AI models were trained on ~80%, validated on ~10%, and tested on the remaining 10% hold out data from Wake Forest Baptist Health (WFBH) ECG repository and externally validated using data from the University of Tennessee Health Science Center (UTHSC).

Results:
The ECG-AI model was developed using 1,078,198 digital ECGs, 114,068 ECHO derived LVEF values, and EHR data from 165,243 patients (73% White, 19% Black, 52% female, with a mean age (SD) of 58(15) years). There were 32,962, 40,997, 11,037, and 993,202 ECGs from 8,555 rEF, 13,116 mEF, 3,704 HFpEF, and 139,868 control patients, respectively. The ECG-AI achieved a hold-out AUC of 0.76 (0.74-0.77) in classifying ECGs as HFpEF or not (Table 1). The UTHSC external validation cohort included 273 rEF, 167 mEF, 459 HFpEF, and 35,254 control patients, with 35% White, 62% Black, 60% female, mean age of 51(18) years. Our model identified HFpEF patients with an AUC of 0.75 (0.73-0.76) in the UTHSC cohort.

Conclusion:
ECG data alone result in moderate, moderately high, and very high accuracies in classifying HFpEF, mEF, and rEF, respectively. This could guide future models with incorporation of simple patient demographics and comorbidities to improve accuracy. Such ECG-AI models can assist with identifying who may benefit from further clinical evaluation and imaging studies.
Abstract 4143554: Ventricular Support Use and Mortality Rates in Cardiogenic Shock Between 2018-2023: A Report from the Northern New England Cardiovascular Disease Study Group
Authors: Rashid Khaldoon , Lin Isabelle , Lutz Daniel , DeVries James
Published: November 2024

Background:
Despite advances in ventricular support devices, increasing awareness and multiple national initiatives to improve survival, mortality from cardiogenic shock remains high. Previous observational studies have shown decreased mortality rates with intra-aortic balloon pump usage over Impella. Relationship between support device use and overall survival in patients with cardiogenic shock remains an area of further investigation.

Aims:
Our objective was to examine the temporal trends in the mortality and ventricular support in patients with cardiogenic shock undergoing PCI in Northern New England from 2018-2023.

Methods:
The NNE registry was queried to identify patients presenting for PCI who manifest cardiogenic shock between 2018 and 2023. Shock was defined by the NCDR definition including sustained hypotension requiring inopressor use. Demographics, procedural data, mortality and intraprocedural ventricular support device use was collected. Standard statistical methods were used to calculate outcomes and statistical significance.

Results:
A total of 842 patients were identified who presented with shock. Overall, in-hospital mortality was 30.9%, and varied from 27.72% in 2018 to 38.3% in 2021 during the height of the COVID-19 pandemic (Figure 1). Mechanical support use remained flat, with an average use of 56% of all cases (Figure 2). The distribution of intra-aortic balloon pumps and Impella devices changed, with Impella use increasing from around 41% in 2018 to 44% by the end of the study in 2023, and intra-aortic balloon pump usage declining from 55% in 2018 to 49% by 2023 (Figure 3). Data was limited to perform a correlation analysis between type of mechanical support device and mortality rates.

Conclusions:
Despite using ventricular support in nearly 60% of cases, in-hospital mortality for cardiogenic shock remains around 30%. Our data reveals a trend towards higher Impella usage with declining intra-aortic balloon pump usage, interestingly with no change in mortality. This warrants further research to better understand how to optimize care for patients presenting with cardiogenic shock.
Abstract 4143604: Efficacy and Safety of Rivaroxaban Versus Low Molecular Weight Heparin for Treating Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis
Authors: Shrestha Abhigan , Mainali Nischal , Shrestha Sajina , Jaiswal Vikash , Rajak Kripa , Hameed Maha , Edara Ravi Sankar Reddy , KC ANIL
Published: November 2024

Background:
Rivaroxaban is a novel oral anticoagulant suggested as an alternative to low molecular weight heparin (LMWH). However, its efficacy and safety compared to LMWH for treating venous thromboembolism (VTE) in cancer patients remain unclear.

Hypothesis:
This study aims to compare the efficacy and safety of rivaroxaban against LMWH for treating VTE in cancer patients.

Methods:
We conducted a literature search for relevant articles on PubMed, Google Scholar, and Embase. Outcomes were pooled using the DerSimonian and Laird random-effects model as risk ratios (RR) with 95% confidence intervals (CI). A p-value of <0.05 was considered statistically significant.

Results:
A total of 14368 cancer patients (Rivaroxaban: 4378 and LMWH: 9990) from 13 studies were included with an average age of 62.5 and 61.9 respectively.

At 3 months, rivaroxaban was associated with a decreased risk of recurrent VTE (RR 0.73, 95% CI: 0.59, 0.86, p<0.05) and bleeding-related hospitalization (RR 0.79, 95% CI: 0.61, 0.97, p<0.05) with statistical signifcant whereas, major bleeding (RR 0.87, 95% CI: 0.09, 1.65), non-major bleeding (RR 0.84, 95% CI: 0.60, 1.08) and all-cause mortality (RR 0.91, 95% CI: 0.72, 1.09) were comparable.

At 6 months, rivaroxaban was associated with a decreased risk of all-cause mortality (RR 0.80, 95% CI: 0.62, 0.97, p<0.05), and bleeding-related hospitalization (RR 0.81, 95% CI: 0.65, 0.98, p<0.05) whereas major bleeding (RR 0.88, 95% CI: 0.52, 1.24), non-major bleeding (RR 0.85, 95% CI: 0.42, 1.29) and recurrent VTE (RR 0.83, 95% CI: 0.64, 1.01) were comparable.

At 12 months, rivaroxaban was associated with a decreased risk of mortality (RR 0.71, 95% CI: 0.50, 0.92, p<0.05), however non-major bleeding (RR 1.38, 95% CI: 0.83, 1.94), cancer-associated thrombosis recurrence (RR 0.94, 95% CI: 0.73, 1.16), and bleeding (RR 0.70, 95% CI: 0.26, 1.15) were comparable.

Conclusion:
While rivaroxaban is associated with low adverse outcomes suggesting its use in treating VTE in cancer patients, further research is recommended.