bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4141652: Duchenne Muscular Dystrophy Boys Have Diastolic Dysfunction Based on Cardiac Magnetic Resonance
Authors: Starnes Joseph , Weiner Jeffrey , GeorgeDurrett Kristen , Crum Kimberly , Henderson Christopher , Campbell Michael , Gambetta Katheryn , Hor Kan , Husain Nazia , Li Jennifer , Raucci Frank , Soriano Brian , Spurney Christopher , Markham Larry , Soslow Jonathan
Published: November 2024

Introduction/Background:
Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). While cardiac magnetic resonance (CMR) is used routinely to assess fibrosis and left ventricular ejection fraction (LVEF), CMR measures of LV filling and ejection in DMD have not been reported.

Hypothesis:
We hypothesized that patients with DMD would have abnormal LV filling and ejection measures compared to healthy controls and that these measures would associate with mortality.

Aims:
We aimed to assess LV filling and ejection curves in patients with DMD compared to healthy controls and whether these measures associate with mortality.

Methods:
Prospectively enrolled DMD patients and healthy controls underwent CMR, including LVEF and LV filling and ejection curves. Multivariable linear regressions were used to compare filling and ejection measures between groups to adjust for baseline differences. Cox regressions were used to evaluate the relationship between diastolic function measures and mortality in the DMD cohort.

Results:
A total of 179 patients with DMD (mean age 14.3 years) and 96 healthy controls (mean age 14.4 years) were included. DMD patients had lower baseline LVEF, though most (112, 62%) had normal systolic function. When adjusted for age, sex, heart rate, body surface area, and left ventricular end diastolic volume (LVEDV), patients with DMD had slower peak LV filling rates (PFR) and peak LV ejection rates (PER) as well as slower time to PER (Table 1). When limited to DMD patients with normal LVEF, PER remained slower. When adjusted for heart rate, lower PER and PFR normalized to LVEDV were associated with mortality in patients with DMD (Table 2).

Conclusions:
Patients with DMD have different baseline CMR filling and ejection indices compared with controls, including when limited to DMD patients with normal LVEF. While filling indices associate with mortality in the short-term, longitudinal follow-up is needed to refine their prognostic role in DMD.
Abstract 4141662: Study of Angiogenic Cell Therapy for Progressive Pulmonary Hypertension: Intervention with Repeat dosing of eNOS-enhanced EPCs: the SAPPHIRE Trial
Authors: Stewart Duncan , Mehta Sanjay , Chandy George , Hirani Naushad , Granton John , Hambly Nathan , Swiston John , Danovitch Kim , Taljaard Monica , Fergusson Dean , Giulivi Antonio , Courtman David
Published: November 2024

In pulmonary arterial hypertension (PAH), widespread pruning of the lung distal arterial bed leads to increased vascular resistance, right heart failure and death. Currently, there are no available therapies designed to revascularize the lung. We assessed the effects of autologous, angiogenic endothelial progenitor cells (EPCs) transfected with endothelial NO synthase (eNOS) in PAH patients receiving available standard-of-care therapies in a 12-month randomized, controlled trial (RCT; NCT03001414). Patients were randomized to receive a course of 4 monthly infusions over the first 6 months consisting of placebo (Arm 1) or eNOS-EPCs (20M cells; Arms 2 and 3) at 0, 1, 2 and 3 months, for a total 80M cells. After 6 months, Arm 1 crossed over to cell infusions, Arm 2 to placebo, whereas Arm 3 received a second course of eNOS-EPCs (total 160M cells). The primary endpoint was change in 6MWD (baseline to 6 months) between patients receiving eNOS-EPCs vs. placebo. However, due to the COVID-19 pandemic the trial was stopped after only 12 of the planned 45 patients were enrolled (5 placebo, 7 cells). While small sample size precluded appropriately powered analyses, a qualitative difference was seen between the eNOS-EPC and placebo groups over the first 6 months (Figure), with a 2-fold greater proportion of patients achieving a 35-meter increase in 6MWD in the cell therapy group (40% vs. 20%, resp). As well, these improvements coincided with cell delivery in all 3 Arms, with a sustained increase in 6MWD over 12 months after a single course of cells in the first 6 months (Arm 2). Treatment with eNOS-EPCs was well tolerated; however, an isolated decrease in 6MWD was apparent 1 month after the first infusion of the second course of cell therapy in Arm 3 patients, with full recovery by the end of the course. This raises the possibility of an immune response to rechallenging patients with this autologous cell product, despite the absence of any clinical indicators, which will be explored by analysis of immune biomarkers. Therefore, the results of the SAPPHIRE trial suggest possible clinical benefit of a single course of 4 infusions of eNOS-EPCs in PAH patients receiving cell therapy and support the performance of a larger RCT.
Abstract 4141670: A blood test based on RNA-seq and machine learning for the detection of steatotic liver disease: A Pilot Study on Cardiometabolic Health
Authors: Poggio Rosana , Rodriguez-Granillo Gaston , De Lillo Florencia , Rubilar Bibiana , Hijazi Razan , Solari Claudia , Rodriguez Varela Soledad , Mobbs Alan , Manchini Estefania , Berdinas Ignacio , La Greca Alejandro , Luzzani Carlos , Miriuka Santiago
Published: November 2024

Background:
Whole blood gene expression is modified in response to signals from various tissues, including the liver. Steatotic (fatty) liver disease (SLD) is a hallmark of cardiometabolic disorder strongly associated with vascular disease (50% of patients undergoing coronary angiography). The main goal of this study was to evaluate the classification performance of peripheral whole blood RNAseq analyzed by artificial intelligence (AI) in identifying or ruling out SLD.

Methods:
The training set consisted of 118 men 40-70 years and women 50-70 years with no history of cardiovascular disease enrolled in a clinical study for assessing coronary artery calcification via a chest computed tomography scan. SLD was defined as <48 Hounsfield Units. Whole blood RNA was isolated and deep sequenced. Different AI models were trained using clinical and transcriptome variables as distinctive features for identifying the presence of SLD. The predictive performance of the combined model (which included transcriptome data, age, sex, BMI, diabetes, and dyslipidemia) was compared against models using only transcriptome data or relevant clinical variables for the presence of SLD. To ensure a robust evaluation of the model's performance, an external validation was conducted using two independent groups (Validation 1 (V1): 32 participants and Validation 2 (V2): 33 participants).

Results:
The prevalence of SLD was 47.5% in the training set, 50% in V1 and 51% in V2 sets. The population variables were as follows (control versus cases): mean age 56 vs. 57 ys; females 26% vs. 29%; diabetes 16% vs. 25%; hypertension 42% vs. 55%; dyslipidemia 23 vs. 34%; obesity 34 vs.57% (p 0.02) and coronary calcium score (mean 96.1 vs. 131.12 Agatston Units, p 0.08). The combined AI model exhibited the highest accuracy for the presence of SLD in the validation set (V2), achieving an area under the curve (AUC) of 0.96 (95%CI 0.90-1.00), sensitivity of 76%, specificity of 94%, positive predictive value of 93%, negative predictive value of 79%, and overall accuracy of 85%. The combined AI model exhibited significant discrimination improvement over the clinical risk model (AUC=0.83; p<0.011).

Conclusions:
In this pilot study, a blood test based on whole blood transcriptome, clinical variables, and AI analysis showed better discrimination ability than clinical risk factors for predicting the presence of steatotic liver disease.
Abstract 4141698: Outcomes of catheter ablation in cardiac sarcoidosis patients with ventricular tachycardia
Authors: al taii haider , Saxena Ritika , Gaalema Diann , Narayanan Chockalingam , Morcos Ramez , Sabayon Muhie Dean , Jneid Hani
Published: November 2024

Background:
Ventricular tachycardia (VT) in patients with cardiac sarcoidosis (CS) can lead to sudden cardiac death. The role of ventricular tachycardia ablation (VTA) in CS has been investigated in a few small, single-center, and some larger observational studies, but the evidence remains scarce.

Hypothesis: We hypothesize that patients with CS have worse cardiovascular outcomes.

Aims: This study aimed to investigate the clinical outcomes of VTA in patients with CS admitted with a diagnosis of VT.

Methods:
A retrospective analysis was conducted using TrinetX database: US collaborative network from 2010-2024. Patients undergoing ablation for VT with and without CS were identified. Two groups were created for propensity score analysis matching on history of hypertension, diabetes, obesity, peripheral vascular diseases, heart failure, ischemic heart diseases, atrial fibrillation, and chronic kidney disease. The primary outcome was incidence of death, cardiogenic shock, heart failure, acute myocardial infarction, hemorrhagic stroke, ischemic stroke, and ventricular tachycardia within one year from the date of the index procedure.

Results:
Results: Out of 15,958 patients who underwent catheter ablation for VT, 776 patients had CS. The mean age of patients with VT and CS who underwent ablation was 58.6 (SD:11.3), compared to 61.1 (SD:15) in patients with VT without CS. In the propensity-matched analysis, there was no significant difference in one-year mortality (hazard ratio (HR) 0.65; 95% CI [0.45, 0.94], χ2 = 3.05, p = 0.08), heart failure (HR 1.18; 95% CI [1.04, 1.33], χ2 = 1.5, p = 0.2), cardiogenic shock (HR 1.33; 95% CI [0.95, 1.89], χ2 = 0.005, p = 0.94), acute myocardial infarction (HR 0.81; 95% CI [0.5, 1.11], p = 0.67), hemorrhagic stroke (HR 0.89; 95% CI [0.18, 4.41], p = 0.42), ischemic stroke (HR 1.18; 95% CI [0.80, 1.7], p = 0.79) or ventricular tachycardia (HR 1.17; 95% CI [1.04, 1.31], p = 0.19)

Conclusion:
This analysis shows there is no significant difference in major complications in patients with cardiac sarcoidosis undergoing catheter ablation for ventricular tachycardia compared to patients without cardiac sarcoidosis.
Abstract 4141704: An Innovative, Non-invasive, Credit-Card Sized Device for Ambulatory 12 Lead ECG Recording: First-In-Human Experience Compared to Standard 12 Lead ECG
Authors: Deering Thomas , Vukajlovic Dejan , Babic Milos , Djurdjevic Branko , Atanasoski Vladimir , Miletic Marjan , Mittal Suneet , Sanders Prashanthan
Published: November 2024

Background:
The multiple electrodes needed to generate a 12-lead electrocardiogram (12L ECG) limits its use to traditional health care settings. An innovative credit-card sized unit (HeartBeam, Santa Clara, CA, USA) when placed on the chest without cables captures a vectorcardiogram (VCG). A personalized transformation matrix (PTM) then converts the signals into a 12L ECG.

Objective:
This is the first quantitative (standard intervals and amplitudes) and qualitative (rhythm diagnosis) accuracy assessment of a synthesized 12L ECG (Syn 12L) compared to a simultaneously recorded standard 12L ECG (Std 12L) on patients in sinus rhythm (SR) or in a non-life-threatening arrhythmia.

Methods:
The 80 patients, who were enrolled at a single center (Dedinje Cardiovascular Research Institute, Belgrade, Serbia), first underwent recording of a Std 12L and VCG to create a unique PTM, which was used to create the Syn 12L from the VCG. Then a simultaneous Std 12L and VCG were recorded. The quantitative endpoint was the calculated difference (mean and standard deviation [SD]) between the Syn 12L and Std 12L in a series of intervals (RR, PQ, QJ, and QT) and amplitudes (P wave, R wave, and T wave). For the qualitative endpoint, 2 blinded electrophysiology physicians (EP) classified the Syn 12L and Std 12L arrhythmia status.

Results:
Of the 80 patients, 41 were in SR and 39 in another rhythm (3:SR with PACs, 5:SR with PVCs, 1:SR with pre-excitation, 16:atrial fibrillation, 3:atrial flutter, 2:atrial pacing, and 9:ventricular pacing). The interval and amplitude differences are listed in the table. Rhythm classification by the blinded EPs demonstrated a sensitivity of 94.9% (95% CI: 82.7-99.4%) and specificity of 100% (95% CI: 91.4-100%) compared to Std 12L.

Conclusion:
In this first study comparing the performance of a 12L ECG created from a credit card sized VCG recorder, the 12L Syn demonstrated clinically equivalent interval and amplitude accuracy and excellent agreement in arrhythmia classification when compared to a simultaneously recorded 12L Std. This approach holds significant promise, potentially permitting patients to obtain a 12L ECG outside of a health care setting with a compact, easy to use device.
Abstract 4141719: Gender Differences in Bleeding Risk and Mortality Following Dual Antiplatelet Therapy Post-Percutaneous Coronary Intervention: A Meta-Analysis
Authors: Alzubi Alhasan Saleh , S. Beshr Mohammed , A. Beshr Ibrahem , Abdelwahed Abdelrahman Farag , Alfaqaih Sarah Mohamed , Abuajamieh Maram , Shembesh Rana Hasen , Kara Arwi Omar , Elfaituri Ahmed , Elsahli Saifaleslam Jamal , Elhadi Muhammed
Published: November 2024

Background:
Dual antiplatelet therapy (DAPT) is widely used following percutaneous coronary intervention (PCI), but it can be associated with bleeding events and adverse outcomes during therapy. This study aims to perform a gender-based analysis of the bleeding risk and mortality associated with DAPT following PCI.

Methods:
On May 15, 2024, we searched the following databases: PubMed, Embase and Cochrane. Our inclusion criteria included any trial or cohort that performed a gender-based analysis of bleeding and mortality outcomes in patients taking DAPT post-PCI. Our outcomes were all-cause mortality, cardiac mortality, and bleeding risk. Bleeding risk was assessed using the Bleeding Academic Research Consortium (BARC) classification, and Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria. We used RevMan with a random-effects model to calculate the effect size, using odds ratios (OR) with a 95% confidence interval.

Results:
Out of the 1,865 articles searched, only 26 papers were eligible for inclusion and analysis. Nine were randomized controlled trials, and 17 were observational cohorts. The total number of patients was 267,986, of which 203,524 were male and 64,436 were female. There was no significant difference in cardiac mortality between males and females; the OR was 0.88 (95% CI: 0.71-1.08, P=0.22). All-cause mortality was reduced in males compared to females, with an OR of 0.81 (95% CI 0.71-0.92, p=0.002). The BRAC 2-5 classification was less likely in males compared to females, with an OR of 0.81 (95% CI: 0.70-0.94, p=0.005). Similarly, in the BRAC 3-5 classification, there was a significant lower probability of bleeding in male compared to female (OR 0.65, 95% CI: 0.52-0.82, p=0.0002). TIMI major bleeding classification was lower in males compared to females, with an OR of 0.61 (95% CI: 0.42-0.88, p = 0.009). This indicates higher rates of major bleeding in females compared to males; and Similar findings were also observed with TIMI minor (OR 0.65, 95% CI: 0.46-0.92, p=0.01).

Conclusions:
These findings highlight the disparities in clinical outcomes of dual antiplatelet therapy following PCI. Females had higher rates of significant bleeding events and all-cause mortality compared to males. This underscores the necessity of investigating the underlying mechanisms driving this gap, emphasizing the need for further research in order to understand and address these differences.
Abstract 4141743: Lipoprotein(a) and Outcomes After Coronary Angiography
Authors: Supriami Kelvin , Andersen Christian , Tello Ayala Roberto , Cho So Mi Jemma , Pomerantsev Eugene , Ellinor Patrick , Honigberg Michael , Fahed Akl
Published: November 2024

Background:
Lipoprotein(a) [Lp(a)] is a potent risk factor for coronary artery disease (CAD) with novel Lp(a)-lowering therapeutics under investigation. Data regarding implications of elevated Lp(a) among patients undergoing coronary angiography are limited. We aimed to assess (i) the association between Lp(a) levels and angiographic characteristics of CAD and (ii) whether Lp(a) levels predict adverse angiographic and clinical outcomes after index coronary angiogram.

Methods:
Patients who underwent coronary angiography and Lp(a) measurement between 2000-2023 were classified into four Lp(a) risk groups: normal (<75 nmol/L), intermediate (75-124 nmol/L), high (125-174 nmol/L), and very high (≥175 nmol/L). Angiographic characteristics (severity, burden, Gensini score—a continuous measure of angiographic CAD burden) and future outcomes starting 3 months after index angiogram (repeat angiogram, revascularization, in-stent restenosis [ISR], heart failure [HF], and all-cause mortality) were analyzed by Lp(a) risk category using Cox proportional hazard models adjusted for age, sex, and race.

Results:
Among 5,118 patients (26.5% female; median [IQR] age 64 [55-74]; 84.9% White), 3,138 (61.3%) had normal Lp(a) levels, 543 (10.6%) intermediate, 464 (9.1%) high, and 973 (19%) very high. Compared to normal Lp(a) levels, very high Lp(a) was associated with obstructive CAD (adjusted odds ratio [AOR], 1.50; 95%CI, 1.16-1.94), multi-vessel disease (AOR,1.79; 95%CI, 1.39-2.30), left-main disease (AOR, 1.80; 95%CI, 1.33-2.45), and a 13.9-point increase in the Gensini score (P<.001). Over a mean follow-up of 11.01±7.58 years, patients with very high Lp(a) were significantly more likely to undergo a repeat angiogram (adjusted hazard ratio [AHR], 1.22; 95%CI, 1.09-1.36), revascularization (AHR, 1.40; 95%CI, 1.19-1.64), and ISR (AHR, 1.34; 95%CI, 1.10-1.63). However, no increased risk of HF was observed (
P
>.05). The risk of mortality was 17% higher in the very high Lp(a) group (95%CI, 1.04-1.32). These trends persisted even after adjusting for baseline CAD burden (
Figure
).

Conclusion:
Very high Lp(a) levels are associated with increased burden and severity of CAD and are strongly predictive of future angiographic and clinical outcomes.
Abstract 4141747: The OurHealth Study: A Decentralized Biobank of South Asian Americans
Authors: Ganesh Shriienidhie , Bhattacharya Romit , Bhatnagar Aarushi , Madnani Rishi , Oruganty Bhaavana , Koyama Satoshi , Patel Aniruddh , Paruchuri Kaavya , Parulkar Sanchita , Bhupathiraju Shilpa , Sengupta Namrata , Khera Amit , Hornsby Whitney , Gulati Martha , Khera Rohan , Palaniappan Latha , Natarajan Pradeep
Published: November 2024

Introduction:
South Asians living in the United States (SAUS) experience greater cardiovascular disease (CVD) events compared to most other racial and ethnic groups. Limited representation and collection of relevant community-specific identity, health, lifestyle, and exposure factors in studies to date have impeded understanding of this elevated risk. To address these scientific gaps, the OurHealth study was devised as a scalable national biobank of SAUS populated with demographic, health, and genetic data.

Aims:
The primary objectives of OurHealth are to discover South Asian-specific genomic and non-genomic risk factors for CVD and serve as a reliable resource of culturally appropriate information for cardiovascular health.

Methods:
OurHealth is enabled by the study platform website (https://ourhealthstudy.org), recruiting adult individuals who (1) identify with South Asian ancestry, (2) are comfortable reading or speaking English, and (3) live in the US. Recruitment efforts include social media outreach, community-based events, clinic recruitment, and health webinars, amongst others. OurHealth integrates the data donation and genomics platforms, allowing participants to remotely consent, complete surveys collecting demographic and health information, and return biospecimens for genetic sequencing.

Results:
Of the 664 participants who have completed the Baseline Survey, OurHealth currently includes 288 (43.4%) females and 19 (2.9%) additionally identifying with non-Asian ethnicity. Study participants’ mean (SD) age is 46 (13.8) years. Participants represent 362 unique South Asian region-language-religion groups with varied representation across the US and several identifying with multiple groups (Fig 1). Of the 615 participants who have completed the cardiometabolic history survey, 39 (6.3%) report a prior diagnosis of coronary artery disease, 237 (38.5%) hypercholesterolemia, 115 (18.7%) hypertension, 11 (1.8%) prior myocardial infarction, and 72 (11.7%) type 2 diabetes.

Conclusions:
OurHealth is an ongoing diverse national biobank building on prior efforts. The study provides a unique opportunity to better discover and understand the drivers of CVD risk across a diverse South Asian population in the US.
Abstract 4141749: Eplerenone: The New Standard in Heart Failure Management-Insights Into Improved Ejection Fraction and Reduced Mortality Compared to Spironolactone: A Systematic Review And Meta Analysis
Authors: Adhikari Ashok , Tadigotla Chandana , Gaddam Ashwith Reddy , Vaghamashi Yogeshkumar , Gupta Umang , Meda Venkata Sai Abhilash , Panjiyar Binay
Published: November 2024

Background:
Mineralocorticoid receptor antagonists namely, Spironolactone and Eplerenone, have been cornerstone therapies for reducing morbidity and mortality in patients with heart failure. However, the comparative efficacy and safety profiles of Spironolactone and Eplerenone in patients with heart failure and reduced ejection fraction have been largely unknown.

Hypothesis:
We hypothesize that Eplerenone is more efficacious and safer than Spironolactone in treating patients with heart failure and reduced ejection fraction.

Methods:
We conducted a comprehensive literature search in electronic databases such as PubMed, GoogleScholar, ScienceDirect, Cochrane library, PLOSONE and Clinicaltrial.gov, including studies published within the last 10 years.We used RevMan 5.4.1 version to make statistical calculations and random effects model to calculate the pooled mean difference(MD) and relative risk(RR) values with their corresponding 95% confidence intervals(CI). A p-value of <0.005 was considered statistically significant.

Results:
A total of 1296 participants (Spironolactone:647 and Eplerenone:649) from three Randomized trials and three cohorts were included in this study. The mean age of participants were 59.74±12.47 and 60.35±10.99 years with 67.12% and 66.52% males along baseline Left Ventricular ejection fraction(LVEF) of 33.47±7.77 and 32.48±8.37% in spironolactone and eplerenone groups respectively. During follow-up, eplerenone improved LVEF(MD,2.96,95%CI:2.12-3.81,I2=0%,p=<0.05), reduced Left Ventricular end systolic volume(MD,-11.50,95%CI:-14.98 to -8.03,I2=0%,p=<0.05), Left Ventricular end diastolic volume(MD,-7.99,95%CI:-15.07 to -0.90,I2=0%,p=0.03) and all-cause mortality(RR,0.70,95%CI:0.52-0.93,I2=0,p=0.02). Although insignificant, eplerenone reduced cardiovascular death or hospitalization(RR,0.95,95%CI:0.79-1.15,I2=0,p=0.60) and safety outcomes like hyperkalemia(RR,0.70,95%CI:0.45-1.09,I2=0,p=0.12) and gynaecomastia(RR,0.18,95%CI:0.02-1.65,I2=71%,p=0.13).

Conclusion:
In patients with heart failure with reduced ejection fraction, compared to spironolactone, eplerenone showed superiority in improving Left ventricular ejection fraction, end systolic and diastolic volumes with all-cause mortality. Although statistically insignificant, eplerenone use reduced the cardiovascular death or hospitalization and adverse events like hyperkalemia and gynaecomastia in male patients. Further, clinical trials and research are necessary to confirm the above findings.
Abstract 4141751: Exercise-Induced Improvements in Capillary Density are Influenced by Sex, Hormone Replacement Therapy, and Exercise Intensity
Authors: Dagher Anna-Maria , Collins Katherine , Ross Leanna , Duscha Brian , Houmard Joseph , Annex Brian , Kraus William
Published: November 2024

Background:
While cardiometabolic disease (CMD) is the top cause of death for US women, age at onset is 10-20 years after that of men largely due to menopausal estrogen loss. Along with premenopausal estrogen, exercise decreases CMD risk in part by increasing capillary density (CD). To better understand CMD risk in postmenopausal women, we investigated the impact of sex, hormone replacement therapy (HRT), and exercise amount/intensity on CD. We hypothesized that compared to women not using HRT and independent of exercise amount/intensity, women using HRT and men would display greater exercise improvements in CD and lesser declines during a detraining period.

Methods:
Previously sedentary adults with overweight/obesity (n=228) were randomized to an inactive control or one of three 6-mo exercise groups: 1) low-amount/moderate-intensity (LAMI); 2) low-amount/vigorous-intensity (LAVI); or 3) high-amount/vigorous-intensity (HAVI). Biopsy-derived skeletal muscle CD was measured at baseline, 24-h-, 4-days-, and 14-days post-intervention (detraining period). Change scores were calculated by subtracting baseline from post-intervention CDs and analyzed using one-way ANOVA and post-hoc by two-tailed two-sample t-tests. The effects of sex, HRT, and exercise group on CD over time were assessed by linear mixed models.

Results:
Exercise significantly increased CD in all groups except LAMI women not using HRT and LAVI men. In vigorous-intensity groups, men increased CD through detraining while women rapidly returned to baseline. With LAMI exercise, CD in women not using HRT and men returned to baseline with detraining. Women using HRT with LAMI, but not vigorous-intensity exercise, sustained CD improvements through detraining.

Conclusions:
Sex, HRT, and exercise intensity impacted CD responses to exercise and detraining. Men and women performing vigorous-intensity exercise display disparate detraining responses, indicating women require continued training to maintain exercise-induced CD improvements. HRT sustained CD improvements through detraining in women performing LAMI but not vigorous-intensity exercise. These findings influence recommended exercise frequency and intensity by sex and HRT use to decrease postmenopausal CMD risk.
Abstract 4141778: Cell Signaling, Metabolic, and Inflammatory RNA Transcriptomic Pathways are Upregulated Among Patients with Coronary Microvascular Dysfunction and Ischemia with Non-Obstructive Coronary Arteries
Authors: Jerome Barbara , Schlamp Florencia , Hausvater Anais , Joa Amanda , Serrano Claudia , Farid Ayman , Hochman Judith , Barrett Tessa , Reynolds Harmony , Berger Jeffrey , Smilowitz Nathaniel
Published: November 2024

Background:
Coronary microvascular dysfunction (CMD) is a cause of ischemia with non-obstructive coronary arteries (INOCA), but mechanisms underlying CMD are not well understood. We previously reported a proinflammatory whole blood transcriptional signature among INOCA patients with versus without CMD. Here we sought to broadly identify pathways beyond inflammation with potential relevance to CMD mechanisms.

Methods:
We prospectively enrolled females with ischemic symptoms or myocardial ischemia on stress testing who underwent invasive coronary angiography with <50% stenosis in all major epicardial vessels. CMD was defined as coronary flow reserve (CFR) <2.5 measured invasively by bolus thermodilution. Whole blood RNA was collected at the time of coronary angiography and sequenced. Differential transcript expression analyses adjusted for age were performed using DESeq2 with CFR as binary and continuous variables. Ingenuity Pathway Analysis (IPA) was performed to identify differentially expressed canonical pathways with nominal p-values <0.05 and a z-score ≥|2|.

Results:
Seven of 28 women with INOCA (mean age 60 ± 8.4 years, 82% white, 32% Hispanic/Latino ethnicity) had CMD. When CFR (median 3.2 [IQR 2.5-4.2]) was analyzed as a continuous variable, 55 pathways were differentially expressed: 6 related to cell adhesion and migration signaling (e.g., integrin signaling) and 13 metabolic processes (e.g., PI3K/AKT signaling). All cell adhesion and migration pathways (
Figure,
Panel A) and 11/13 metabolic pathways (Panel B) were upregulated with lower CFR. As previously reported, 18/19 pathways related to inflammation were upregulated (Panel C). The remaining 17 pathways were related to the immune response to specific pathogens, the cell cycle and tumorigenesis, and signaling in the gastrointestinal, nervous, and endocrine systems.

Conclusion:
Pathways related to cell signaling, metabolism, and inflammation were primarily upregulated among women with INOCA and CMD versus those without CMD. Further research is needed to explore transcriptional profiles implicated in the pathogenesis of CMD in INOCA.
Abstract 4141811: Determining the Accuracy of Sleep and Activity Patterns in Patients Undergoing Long-Term Ambulatory ECG Monitoring
Authors: Bogan Richard , Yu Elaine , Mysliwiec Vincent , Miller Mitchell , Kacorri Ardit , Tamura Yuriko , Battisti Anthony , Fokin Vladimir , Hytopoulos Evangelos , Gilbert Andrew , Bame Charlotte , Turakhia Mintu
Published: November 2024

Background:
Ambulatory ECG (AECG) enables heart rhythm monitoring during daily activities, with a focus on arrythmia detection. Detection and quantification of sleep and activity patterns during monitoring may provide insights into lifestyle and aid in contextualizing arrhythmia events.

Aims:
We developed an AI algorithm to classify sleep, activity, and inactivity periods using a novel AECG patch with embedded accelerometry. We assessed algorithm performance and compared it to FDA-cleared actigraphy and consumer devices, which have shown 93-99% sensitivity (SE) and 39-54% specificity (SP) in classifying sleep vs. polysomnography (PSG).

Methods:
We conducted a prospective study of 81 participants at 3 sites who wore the Zio
®
monitor AECG patch (iRhythm Technologies, San Francisco, CA) and Actigraph wGT3X (Pensacola, FL) simultaneously for 14 days. Sleep disordered breathing was excluded. Participants underwent a 6-minute walk test at the beginning of wear and in-clinic overnight PSG sleep testing at 7±3 days.

Data were split into training (n=40) and validation (n=41) sets. Feature and model selection utilized five-fold cross-validation on the training set, focusing on total activity and body angle. The final machine model was trained on selected features using the entire training set. In validation, SE and SP for sleep were assessed based on 1-minute epochs vs. PSG and also vs. a 24-hour reference (combined PSG and actigraphy-wake labeling). SE and SP for activity were assessed vs. actigraphy over 8 minutes sampled per subject (4min walk test, 4min PSG wake periods).

Results:
The study population was diverse (age 43±14 years, 57% female, 64% White, 25% Black, 20% Hispanic). In the validation set, average sleep and wake times were 5.9 and 1.2 hours, respectively, during PSG. SE and SP were 88.8% and 54.0%, respectively, in sleep detection vs. PSG, or 88.8% SE and 95.6% SP vs. the 24-hour reference (Table 1). SE and SP for activity detection were 97.0% and 100%, respectively.

Conclusion:
Assessment of sleep and activity during AECG is feasible, with performance comparable to FDA-cleared actigraphy. This feature offers insights into patient wellness patterns, highlighting its potential for personalized healthcare monitoring.
Abstract 4141831: Estimating Time to Incidence and Progression of Cardiovascular-Kidney-Metabolic Multimorbidity: A Large-Scale Longitudinal Cohort Study
Authors: Ostrominski John , Hirsch Jamie , Miao Benjamin , Clark Brendan , Donato Bonnie MK , Woolley Jonathan , Parrinello Christina , O'Connell Thomas , Vaduganathan Muthiah
Published: November 2024

Background:
Cardiovascular-kidney-metabolic (CKM) conditions, such as heart failure (HF), chronic kidney disease (CKD), and type 2 diabetes (T2D), commonly coexist. However, whether specific pathways and timing of CKM multimorbidity onset and progression vary in relation to background CKM status has not been rigorously evaluated.

Methods:
In this retrospective cohort study using Optum Market Clarity, a longitudinal (2007-2023) US database comprising electronic health records of >80M unique individuals linked to claims, we estimated incidence rates of CKM conditions (clinical cardiovascular disease [cCVD; myocardial infarction, stroke, peripheral artery disease, and atrial fibrillation], HF, CKD, and T2D) and multimorbidity (≥2 CKM conditions). CKM conditions were identified via administrative codes and/or laboratory data. Time-to-onset and progression of CKM multimorbidity was evaluated by baseline CKM status (number/type of CKM conditions), using Cox proportional hazards models.

Results:
Overall, 604,732 individuals were included in the analysis (mean [SD] age, 48.4 [17.1] years; 56% female), of which 136,886 (23%) had ≥1 CKM condition at baseline. In patients with 1 CKM condition, HF was associated with the highest rate of progression to CKM multimorbidity (incidence rate, 15.99 per 100 patient-years), followed by CKD, cCVD, and T2D (
Figure, A
). Among those who experienced progression to CKM multimorbidity, median times to a second CKM condition ranged between 1.2 to 2.0 years. When the full spectrum of baseline CKM status was evaluated, rates of multimorbidity progression and all-cause death generally increased with higher baseline CKM burden (
Figure, B
). However, progression of CKM multimorbidity varied by background CKM status; cCVD and T2D occurred most frequently among those without CKM conditions, HF and T2D occurred most frequently among those with cCVD, and cCVD occurred most frequently among those with HF, CKD, and T2D.

Conclusions:
These findings provide novel insights into pathways and timing of CKM multimorbidity progression in the US, stressing the need for intensive management strategies to prevent or delay the often rapid onset of sequential CKM conditions once one is established.
Abstract 4145344: Outcomes of Early Rhythm Control versus Rate Control Strategies for Atrial Fibrillation in Elderly Patients: A Systematic Review and Meta-Analysis
Authors: Ahmad Soban , Ahsan Muhammad , Kim Kathryn , Fazeel Hafiz Muhammad , Cheema Huzaifa Ahmad , Yousaf Amman , Khalil Laraib , Ikram Sundus , Kim Michael
Published: November 2024

Background:
The prevalence of atrial fibrillation (AF) increases with age. However, limited data are available regarding the prognostic implications of rhythm versus rate control strategies for AF in the elderly. We have conducted this systematic review and meta-analysis to explore the effects of early rhythm control strategy in elderly (age >65 years) AF patients.

Methods:
A literature search was conducted for relevant studies using MEDLINE (PubMed), EMBASE, Scopus, Cochrane CENTRAL, Conference Abstracts, and ClinicalTrials.com through March 19th, 2024. The primary outcome was all-cause mortality. Meta-analysis was performed using the random-effects Mantel-Haenszel method, and pooled risk ratios (RRs) along with 95% confidence intervals (CIs) were calculated using RevMan 5.4.

Results:
Six studies with 39,181 patients (rhythm control 11,446; rate control 27,735) were included. The mean age was 79 years in the rhythm control and 81 years in the rate control cohort. Females were 52% in rhythm control and 55% in the rate control group. The rhythm control strategy was associated with a lower risk of stroke (RR 0.73, 95%CI 0.66-0.81, p<0.0001, I
2
=44%) but had a higher risk of permanent pacemaker (PPM) implantation (RR 2.54, 95%CI 1.04-6.23, p=0.04, I
2
=29%). Rhythm control did not improve all-cause mortality (RR 0.90, 95%CI 0.72-1.11, p=0.32, I
2
=96%) or cardiovascular mortality (RR 0.87, 95%CI 0.62-1.23, p=0.43, I
2
=75%) in elderly AF patients.

Conclusion:
Rhythm control strategy in elderly patients is associated with a lower risk for stroke but has a higher risk for PPM implantation. Additionally, there is a comparable risk for all-cause mortality and cardiovascular mortality between rhythm and rate control treatments for elderly AF patients.
Abstract 4145352: SGLT2 Inhibitor-Induced Euglycemic Ketoacidosis in a Non-Diabetic Patient with Ischemic Cardiomyopathy
Authors: Khadka Sulochana , Rajak Kripa , Matai Pallavi , Timilsina Bibek , Sharma Seema , Halder Anupam , Calderon Martinez Evelyn , Jaiswal Vikash
Published: November 2024

Introduction:
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are drugs designed to lower plasma glucose concentration by inhibiting Na
+
-glucose–coupled transport in the proximal tubule. Clinical trials demonstrate these drugs have favorable effects on cardiovascular outcomes including including slowing the progression of CKD. Although most patients tolerate these drugs, a potential complication is development of ketoacidosis, often with a normal or only a minimally elevated plasma glucose concentration mostly in diabetic patients. We present a case of SGLT-2 inhibitor induced ketoacidosis in a patient without any risk factor.

Case Presentation:
The patient is a 56-year-old gentleman without significant past medical history who presented to the emergency room with prolonged chest pain for more than 12 hours. He was hemodynamically stable with EKG evidence of acute Q-wave and ST elevation in the anteroseptal leads and high sensitivity troponin of about 78,000. He underwent successful PCI along with placement of two DES at mid LAD and proximal OM. Transthoracic echocardiography post catheterization showed LVEF of 25% with dyskinetic apical and apical inferior segment. Subsequently, GDMT for ischemic cardiomyopathy. Approximately after two days of initiation of GDMT, he was noted to have low bicarbonate of 18 and an AG of 16 following which ABG was drawn that showed metabolic acidosis with a nadir pH of 7.30 and an associated Pco
2
level of 29 mmHg. Despite an abnormal lab, he was clinically asymptomatic with no active complaints. His A1C was found to be 5.4. UA revealed ketones (2+) without glucose. β-Hydroxybutyrate level was elevated to 3.34 mmol/L. On further review of his chart, we saw that he had received two doses of empagliflozin. Diagnosis of euglycemic ketoacidosis, presumably related to SGLT2 inhibitor therapy was made. Endocrinologist recommended the usual management like diabetic ketoacidosis. The patient was then started on dextrose and insulin drip. Following closure of anion gap, drips were discontinued. Later, the patient was discharged home on GDMT without SGLT2 inhibitor.

Conclusion:
Given the tremendous benefits of SLGT-2 inhibitors in patients with diabetes, heart failure, and CKD, their use is expected to grow significantly. Providers should remain vigilant for potential evidence of the development of euglycemic ketoacidosis even in nondiabetic patients using SGLT-2 inhibitors, so that appropriate intervention is done in a timely manner.
Abstract 4145384: Incidence of Necrotizing Enterocolitis (NEC) in Infants with Congenital Heart Disease on the Acute Care Cardiology Unit (ACCU): A Report from the Pediatric Acute Care Cardiology Collaborative (PAC3)
Authors: Duncan Rachel , Patel Sonali , Marcuccio Elisa , Harahsheh Ashraf , Favilla Emmanuelle , L'italien Kaitlin , Sagiv Eyal , Strohacker Courtney , Schiller Amy , Tierney Jenifer , Williams Suzanne , Weiner Jeffrey
Published: November 2024

Introduction:
Necrotizing enterocolitis (NEC) is a life-threatening condition of compromised gastrointestinal mucosa with risk of progression to ischemia, necrosis and perforation. The incidence and outcomes of NEC in infants with congenital heart disease (CHD) are incompletely understood.

Hypothesis:
Patients who develop NEC in the acute care cardiology unit (ACCU) are likely to have different patient characteristics and worse clinical outcomes than those who do not develop NEC.

Aims:
Describe differences in baseline characteristics and clinical outcomes in infants
<
6 months of age with CHD in the ACCU who suffered NEC compared to those who did not.

Methods:
Data were analyzed from the Pediatric Acute Care Cardiology Collaborative (PAC
3
) database. All patients
<
6 months were included. Patients who had NEC (Bell’s stage ≥2) on the ACCU were compared to those who did not.

Results:
In 29041 patient encounters from 16770 unique patients across 33 centers, the incidence of NEC was 1.5%. Patients with NEC were more likely to have extracardiac abnormalities, antenatal diagnosis and have undergone procedural intervention (Table 1). Patients who developed NEC had longer lengths of stay and higher rates of mortality, CICU transfer and readmission (Table 2). In addition, patients who developed NEC had lower rates of oral feeding at encounter end. Of 14823 patients in their post-surgical encounter, those who developed NEC were significantly more likely to have undergone a more complex index procedure and to be younger, lower weight and on prostaglandin at the time of surgery. Patients who developed NEC were more likely to be on anticoagulation, ACE-inhibitors, anti-reflux medications, milrinone, diuretics and anticonvulsants.

Conclusion:
In this original multicenter analysis, patients who developed NEC on the ACCU had different characteristics and significantly worse clinical outcomes. Further study is warranted to identify risk factors for NEC in this vulnerable population.
Abstract 4145406: The Outcome of Acute Pulmonary Embolism in the Population with Preexisting Atrial Fibrillation
Authors: Mir junaid , Al-Ahmad Majd , Nandu Nitish Singh , Basharat Anam , Basit Jawad , Alraies M Chadi
Published: November 2024

Background:
Atrial fibrillation (AF) is the most common arrhythmia. Patients with AF are at high risk of pulmonary embolism (PE). Similarly, patients with PE are at high risk of AF. There is scarcity of data regarding the outcomes of acute pulmonary embolism in the patients with preexisting AF.

Methods:
This is an analysis of the National Inpatient Sample of the years 2016 to 2020. We identified patients who were admitted with PE using ICD-10-CM codes. We divided the population into two groups by secondary diagnosis of AF. The risk of mortality and in-hospital complications in the PE/AF group was compared to the PE/non-AF group using multivariate logistic regression analysis.

Results:
During 2016-2020, there were a total of 934225 patients who were admitted with PE, of which 102705(11%) patients had AF. After adjusting for demographics, hospitalized PE patients with AF had higher odds of mortality (aOR (adjusted odds ratio) 1.40; 95% CI 1.30–1.52 p < 0.001), GI bleed (aOR 1.30; 95% CI 1.18–1.43p < 0.001), cardiogenic shock (aOR 1.83; 95% CI 1.64 – 2.04 p< 0.001), cardiac tamponade (aOR 2.93; 95% CI 1.88–4.57 p<0.001) ,cerebral infarction (aOR 1.42; 95% CI 1.21–1.67 p< 0.001),AKI (aOR 1.23; 95% CI 1.18–1.29 p< 0.001), respiratory failure (aOR 1.22; 95% CI 1.18–1.27 p< 0.001), longer LOS (aMD (adjusted mean difference) 0.84 days; 95% CI 0.76– 0.92 days p< 0.001) and higher total cost of care (aMD 9987$; 95% CI 8799 – 11173$ p< 0.001) compared to PE patients without AF. (Figure 1)

Conclusion:
Hospitalized PE patients with preexisting AF have higher odds of mortality, GI bleed, cardiogenic shock, cardiac tamponade, cerebral infarction, AKI, respiratory failure, longer LOS, and higher total cost of care compared to PE patients without AF. Physicians should be aware of this prognostic effect of AF and include AF in risk stratification of patients with PE.
Abstract 4145416: Geographic Variation in the Impact of Rurality on Hospitalization for Acute Myocardial Infarction Among Medicare Beneficiaries
Authors: Kanneganti Nitin , Dalmacy Djhenne , Rabah Abdullah , Quadri Fayz , Tiruneh Yordanos , Berry Jarett
Published: November 2024

Background:
Prior research has observed a higher cardiovascular mortality rate in rural vs. urban counties. However, rural counties exhibit significant heterogeneity both within and across geographic regions. Therefore, we sought to characterize the association between rurality and hospitalization for acute myocardial infarction (AMI) across rural vs. urban zip codes and across US Census regions.

Methods:
We included fee-for-service Medicare beneficiaries with prevalent hypertension (HTN) or diabetes (DM), followed from 2017-2021. Participants were categorized at the residential zip code level as metropolitan, micropolitan, small town, and rural using Rural Urban Commuting Area Codes. Census geographic regions were categorized at the state level into Northeast, South, Midwest, and West. First hospitalization for AMI was determined from Medicare claims. The association between rurality and AMI hospitalization was estimated using Cox models adjusted for age, race, and sex. Additional models were stratified by census regions.

Results:
We included 25,915,862 participants (age 73; 45% male; 97.6% HTN; 41.6% DM; 75.5% metropolitan). HTN prevalence was similar across RUCA codes (98%), but DM prevalence was slightly lower (42% vs. 39%, metropolitan vs. rural). After mean follow-up of 3.9 years, we observed 1,395,853 first AMI events (14.3 per 1,000 person-years. Rates were higher in rural vs. metropolitan zip codes (15.6 vs. 13.8 per 1,000 p-years). AMI rates also varied by census region (Northeast: 16.3; Midwest: 15.9; South: 15.5; Midwest: 13.4 per 1,000 p-years). In adjusted models, more rural zip codes were associated with a higher risk of AMI (see Table). However, this association appeared to vary by US census region (see Table).

Conclusion:
Medicare beneficiaries residing in rural communities have a higher risk for AMI compared to those in metropolitan areas. However, these associations do not appear uniform across geographic regions, indicating heterogeneity in the impact of rurality on AMI hospitalization. Further research is needed to understand the factors contributing to this variation.
Abstract 4145437: Factors Associated with the Development of Incident Chronic Hypertension in the Postpartum Period: An Electronic Medical Record Analysis
Authors: Lewey Jennifer , Zhao Manyun , Sheehan Megan , Burris Heather , Cohen Jordana , Levine Lisa , Chen Jinbo
Published: November 2024

Background:
Hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension, are associated with increased risk of cardiovascular disease (CVD) later in life. This effect is strongly mediated by the subsequent development of chronic hypertension (HTN). Our objective is to identify clinical factors associated with incident HTN in a racially diverse cohort of postpartum patients using electronic health record (EHR) data.

Methods:
We identified patients with a delivery at Penn Medicine between 2012 and 2020 who did not have chronic HTN prior to delivery. The primary outcome was HTN between 6 and 24 months postpartum. HTN was identified based on ≥1 ICD code or ≥2 blood pressures (BP) ≥140/90. Univariable and multivariable logistic regression was used to model the association between patient factors assessed during pregnancy through the 6-week postpartum visit and incident HTN.

Results:
In the final cohort of 34,074 unique patients, mean age was 29.6 years, 42% identified as Black, and 38% had Medicaid insurance. A total of 1,078 patients (3.2%) developed incident HTN between 6 and 24 months postpartum. HTN was more common in patients with HDP compared to those without HDP (8.6% vs. 1.6%, p< 0.001). Factors independently associated with HTN are listed in the Table. After adjusting for patient demographics and clinical factors, older maternal age, Black race (vs. White race), preterm birth, obesity, diabetes, HDP, and 6-week postpartum systolic BP (SBP) were associated with HTN. HDP (OR 3.8, 95% CI 3.2, 4.5) and pre-pregnancy BMI ≥35 kg/m2 (OR 2.2, 95% CI 1.8, 2.7) were associated with the highest odds of incident HTN. Every 1 mmHg increase in postpartum SBP was associated with a 6% higher odds of incident HTN, after adjusting for HDP and other clinical factors.

Conclusions:
Patient factors that are routinely collected in the EHR, including HDP and BMI, are strongly associated with increased risk of developing incident HTN between 6-24 months postpartum in a racially diverse cohort. SBP at 6-weeks postpartum is an independent and underappreciated risk factor for HTN. Future work will develop and validate prediction models of incident postpartum HTN in this population at risk for CVD.