bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4140488: Late Gadolinium Enhancement CMR Tissue Characterization for Central Venous Catheter Associated Right Atrial Thrombus – Structural Risk Factors and Stratification of Embolic Outcomes among Systemic Cancer Patients
Authors: Axman Rachel , Schesing Kevin , Tomy Noel , Tsay Annie , Manning Keefe , Reza Mahniz , Kim Jiwon , Liu Jennifer , Weinsaft Jonathan , Chan Angel
Published: November 2024

Background:
Central venous catheters (CVC) are common in cancer pts but provide a nidus for right atrial thrombus (RA-Th). CMR can identify presence and risk factors for RA-Th.

Objectives:
To evaluate predisposing factors and embolic risk conferred by RA-Th.

Methods:
The population comprised adult (≥18yo) cancer pts with CVC who underwent CMR at two sites; RA-Th was defined by avascularity on LGE-CMR. Registry data included clinical and CVC indices and chart review for pulmonary embolism (PE) 1 month pre- or 6 months post-CMR.

Results:
211 pts with CVC (52±17yo; 45% M) were studied, inclusive of RA-Th and controls matched for cancer etiology/stage (heme 28%| GI 27%| sarcoma 22%). CVC type varied (Mediport 81% |PICC 9%| pheresis 6%| HD 4%), as did time between RA-Th and catheter insertion (6.5[2.4-15.8] mo). Pts with and w/o RA-Th were of similar age, sex, CVC type/duration, and cardiac function on CMR (p=NS). CVC depth was greater in pts with RA-Th (2.8±1.6cm vs. 1.5±1.6cm, p<0.001). Prevalence of RA-Th increased in proportion to CVC depth (<1|1-3|>3cm from SVC-RA: 31%|57%|75%; p<0.001 without influencing RA-Th size (p=NS). Anticoagulation (LMWH 42%| NOAC 25%| warfarin 3.4%| combination 26%) was more common in pts with RA-Th (99% vs. 43%; p<0.001). Despite this, RA-Th was strongly associated with embolic risk, as shown by >5-fold higher incidence of PE vs. controls (16% vs 2.5%, p=0.002; OR=7.08 [CI 1.58–31.78], p=0.01;
Table 1
). In pts with RA-Th and PE (n=17), majority of PE (59%) occurred within 1mo of CMR, and the remaining occurred within 1-6mo after CMR (
Fig 1
). Among pts with RA-Th, the likelihood of PE increased with high lesion mobility (27% vs 10%, p=0.02; OR=3.38 [CI 1.13–10.1], p=0.03).

Conclusions:
Increased catheter depth increases risk for RA-Th implicating mechanical factors as a key thrombogenic driver. Despite anticoagulation, patients with RA-Th are at markedly higher risk for embolic events, particularly within the first month of detection on CMR.
Abstract 4140503: Artificial Intelligence Can Match Atrial Fibrillation Electrograms to Action Potential Recordings in Patients
Authors: Abad Juan Ricardo Carlos , Anbazhakan Suhaas , Ruiperez-Campillo Samuel , Rodrigo Miguel , Narayan Sanjiv
Published: November 2024

Background:
In patients with atrial fibrillation (AF), pulmonary vein isolation (PVI) improves morbidity and mortality compared to anti-arrhythmic medications, yet is suboptimal in >30-40% of patients typically with persistent AF. Several promising mapping approaches are emerging for such patients, but results are inconsistent. One challenge is to reconcile differences between clinical mapping of electrograms and optical mapping, that detects local tissue action potentials.

Hypothesis:
We hypothesized that artificial intelligence (AI) algorithms applied to AF electrograms recorded from clinical catheters can infer onsets of action potentials, referenced to clinical MAP recordings.

Methods:
In N=303 AF patients at ablation (68.2±8.0 years, 17.8% females, 72.9% non-paroxysmal AF), we isolated a development cohort (N=229) and a test cohort (N=74). In the development cohort we trained a multistage AI-system to identify cycle-to-cycle activations in AF electrograms recorded from various clinical catheters. In the separate test cohort, we assessed the accuracy of the AI algorithm relative to MAP onsets, recorded at adjacent sites with dedicated catheters (N=20, MedFact, GmbH). We related accuracy to signal quality, defined from the homogeneity of distribution of activation times.

Results:
Figures shows unipolar AF EGMs, MAPs and AI annotation.
A.
Good agreement between AI timing, and MAP onsets (15 ms) for signals of high quality in a 67 year old woman.
B.
Good agreement between AI timings and MAP onsets (42 ms) with delay reflecting spatial separation between EGM and MAP catheters in a 72 year old woman.
C.
Good agreement despite difficulty in expert annotation of EGM in cases of intermediate to low signal quality in a 67 year old man. In summary, the AI system provided an average F1-score for AF timings of 0.83 relative to experts (p<0.01), varying from 0.72 to 0.95 for low to high signal quality (p<0.01). A similar trend was found for AI accuracy vs. MAP onsets (p<.05)

Conclusions:
In this large registry, a novel AI-based approach accurately identified AF activation relative to tissue action potential onsets, referenced to expert labels. AI may improve characterization of AF activity within the atria, and could be a foundation for future mapping and phenotyping.
Abstract 4140505: Sex-Based Disparities in the Care of Syncope Patients in the United States Using a National Database
Authors: Devaguptapu Priyanka , Bai Chen , Petersen John , Smoot Madeline , Edwards Emily , Kamisetty Sujay , Mardini Mamoun , Ruzieh Mohammed
Published: November 2024

Introduction:
Syncope is a common condition often leading to testing and hospital admissions. Research assessing sex-based differences in the workup as well as disposition following emergency department (ED) syncope visits is scarce. In this study, we sought to address this gap using a national database.

Methods:
From 2010 to 2019, we identified syncope patients using ICD-9 and ICD-10 codes. Using data from the IBM MarketScan Research Database, which captures de-identified individual-level health data from approximately 100 commercial payers and self-insured corporations in the United States, we assessed the incidence of testing using CPT codes in the 3 months following syncope diagnosis. Furthermore, we evaluated the percentage of syncope patients discharged from the ED. Sex-based comparisons were performed using the Chi-square test.

Results:
A total of 557,416 patients (54.0% women) were included in the cohort to assess for testing disparities (these are the patients who had at least 3 months of continuous enrollment following syncope diagnosis). Compared to men, women had significantly lower testing in most domains: long-term monitoring (6.8% vs. 7.4%), echocardiogram (13.3% vs. 17.2%), cardiac stress test (4.0% vs. 7.4%), chest X-ray (17.7% vs. 25.5%), imaging for pulmonary embolism (1.5% vs. 2.0%) and carotid Doppler ultrasound (5.4% vs. 7.3%); p< 0.001 for all above comparisons, figure 1A. Tilt table testing was similar between both sexes (1.4% vs. 1.3%).

A total of 1,325,023 patients (58.1% women) were included in the ED disposition cohort. Women presenting to the ED with syncope were more likely to be discharged compared to men (78.7% vs 72.1%; p< 0.001), and this trend remained consistent throughout the study period, figure 1B.

Conclusion:
Women presenting with syncope are less likely to receive testing compared to men, and more likely to be discharged from the ED. There is a need to evaluate the reasons behind these disparities and assess their impact on patients’ outcomes.
Abstract 4140516: Systemic Inflammation Increases 30-Day Mortality of Patients with ST-Segment Elevation Myocardial Infarction
Authors: Cuéllar Vargas Jorge , Torres Ramirez Perla Lizeth , Malchan Eduardo , Araiza Diego , Sierra Lara Martinez Jorge Daniel , Briseño Jose Luis , Gopar-Nieto Rodrigo , Arias Alexandra , González Pacheco Héctor
Published: November 2024

Background:
The inflammatory response plays a crucial role in various aspects of acute coronary syndrome. However, there is limited data associating a validated inflammation risk score and overall mortality prediction in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI).

Hypothesis:
We hypothesize that patients with STEMI exhibiting a severe inflammatory profile undergoing primary PCI have a higher incidence of all-cause mortality within 30 days.

Methods:
This retrospective cohort study obtained from the Coronary Care Unit of a tertiary center in Mexico, included 2,473 patients with acute STEMI who underwent pPCI between October 2005 and December 2023. We employed an inflammation score which comprises: high-sensitivity C-reactive protein (≥ 13.0 mg/L), white blood cell count (≥ 9.3 x10
3
/µL), and serum albumin level (≤ 3.6 g/dL) upon admission. We categorized systemic inflammation into four distinct levels. Mortality risk across these cohorts was compared using the Kaplan-Meier method.

Results:
The cohort included 248, 1035, 851, and 339 patients with no, mild, moderate, and severe inflammation, respectively. A significant proportion of the sample (76.3%) displayed mild to moderate inflammation, underscoring its prevalence in the studied population. Notably, 13.7% exhibited severe inflammation, potentially indicating high-risk groups. At the 30-day follow-up, patients with severe inflammation exhibited the highest mortality rates (
Image 1
; 1.2% vs. 2.5% vs. 5.4% vs. 13%, respectively; Log-rank p<0.001). The hazard ratio for mild inflammation is 2.07 (95% CI, 0.605-7.08; p=0.2), for moderate inflammation it is 4.47 (95% CI, 1.36,-14.69; p<0.05), and for severe inflammation it is 10.73 (95% CI, 3.65-31.27; p<0.0001) compared to the no inflammation group.

Conclusions:
The observed prevalence of inflammation across the studied population suggests a prevailing inflammatory trend influenced by underlying medical conditions, social factors and the STEMI process itself. We suggest a noteworthy association between heightened systemic inflammation during the acute phase of STEMI and increased overall 30-day mortality risk in patients undergoing pPCI.
Abstract 4140528: Association of Ventricular Arrhythmias with Lamotrigine: An Observational Cohort Study
Authors: Kim Sodam , Welch Landon , De Los Santos Bertha , Radwanski Przemyslaw , KIM KIBUM , Munger Mark
Published: November 2024

Objective:
The chemical reduction of intracellular sodium through inhibition of the voltage-gated sodium channels stabilizes presynaptic neuronal membranes and inhibits presynaptic glutamate and aspartate release making lamotrigine (L) an important strategy for treating patients with Bipolar I disorder (BPI). L also slows cardiac conduction velocity introducing a potential substrate for its proarrhythmic properties. This study’s aim was to examine the association between onset of ventricular tachycardia (VT) and L in patients with BPI.

Methods:
A retrospective observational research study was performed using Merative MarketScan
®
Commercial Claims and Medicare Supplemental Database. Analytic cohort included adult naïve VT or atrial fibrillation patients who filled a prescription for L or control agents (C), including lithium, quetiapine, valproate, or risperidone. Patients were free from arrhythmia, including atrial fibrillation or VT, during the 6-month baseline period before prescription of L or C prescription. The onset of VT was identified by the appearance of newly recorded ICD codes. Cumulative incidence of VT was calculated using Kaplan-Meier estimator, with patients being censored at the last enrollment, treatment switching, discontinuing treatment, or end of one-year follow up. We used a multivariable regression model to calculate hazard ratio for the onset of VT associated with L and C, adjusting for baseline characteristics, with a particular interest in the impact of structured heart disease (SHD).

Results:
The analytic cohort included 153,852 L and 213,593 C patients with respective mean year age of 37.53 (SD 13.63) and 40.85 (SD 15.74). The 1-year cumulative incidence of VT from L and C was 0.785% and 0.683%, respectively, calculating HR of 1.270 [95% CI: 1.079-1.496], p=0.0041. Figure 1) (After adjusting for the baseline characteristics, HR was 1.326 [1.122-1.568], p-value = 0.0009. From the multivariable analysis, the measure of SHD impact on the onset of VT was HR of 1.538 [1.011-2.341] (p=0.0444).

Conclusions:
In adult BPI patients, L has a strong potential to increase the risk of VT compared to C. Notably, baseline SHD has a significant impact on the onset of VT.
Abstract 4140554: Epigenetic Activation of Endothelial to Mesenchymal Transition Links Endothelial Dysfunction to Atrial Fibrillation in Lamin A/C Cardiomyopathy
Authors: Owais Asia , Chen Hanna , Barney Miles , Sridhar Arvind , Baskaran Abhinaya , Kortan Elif , DeSantiago Jaime , Arif Mahmud , Islam Abul , Maienschein-Cline Mark , Ong Sang , Darbar Dawood
Published: November 2024

Introduction:
Accumulating evidence supports a bidirectional association between atrial fibrillation (AF), and endothelial cell (EC) dysfunction; however, the underlying mechanisms remain elusive. Variants in
LMNA
, which encodes the nuclear envelope protein Lamin A/C, have been linked with AF. It is known that
LMNA
variants can cause atherosclerotic changes in blood vessels and increase the risk for stroke, however, it remains unclear if endothelial dysfunction creates an arrhythmogenic substrate for AF in the atria.

Hypothesis:
LMNA
-S143P mutation induces endothelial to mesenchymal transition
(
EndMT) in ECs which creates an arrhythmogenic substrate for AF by extracellular matrix (ECM) and ion channel remodeling.

Methods:
We generated and co-cultured human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) and atrial cardiomyocytes (hiPSC-aCMs) from a large family harboring a pathogenic
LMNA
-S143P mutation (
Fig.
A-B
) and performed functional characterization by an angiogenesis assay. Analysis of action potential duration (APD)
(Fig. B)
was performed by optical voltage mapping. Transcriptomic and epigenetic analysis was performed by RNA-sequencing and assay for transposase accessible chromatin and sequencing (ATAC-seq).

Results:
LMNA
-S143P hiPSC-ECs show hallmarks of EC dysfunction with reduced angiogenesis (
Fig.
C
), gene expression signature of EndMT, upregulation of ECM remodeling genes and downregulation of endothelial genes (
Fig.
E
). Upstream regulator analysis identified TWIST-1 as a driver of EndMT
(Fig. F)
. ATAC-seq showed increased open chromatin at genes related to EndMT and identified TWIST-1 as one of the most significantly enriched transcription factors (
Fig.
G-I
). Upregulated ATAC peaks were associated with inflammation and fibrosis pathways (
Fig. H
). Co-culture of
LMNA
-S143P hiPSC-ECs with wild-type hiPSC-aCMs induced APD heterogeneity (SD=0.03, 0.2, 0.01 for WT,
LMNA
-S143P, CRISPR-GC respectively, p<0.05, n=6) (
Fig.
D
). These changes were rescued by the CRSIPR-GC hiPSC-ECs.

Conclusion:
Our results suggest that epigenetic-driven EndMT due to a
LMNA
-S143P mutation promotes inflammatory and fibrotic remodeling in the atria and we identified TWIST1 as a potential therapeutic target.
Abstract 4140556: Comparison of the Risk of Cardiovascular Disease Between Degarelix Versus Gonadotropin-Releasing Hormone Agonists: a Systematic Review and Meta-Analysis
Authors: Hoffmeister Nathalia , Rocha Dantas Clara , Kelly Francinny , de Oliveira Macena Lobo Artur , Menegaz de Almeida Artur , Kendi Tsuchiya Sano Vitor , A de Moraes Francisco Cezar
Published: November 2024

Background:
Degarelix is a third-generation GnRH receptor antagonist approved for the treatment of prostate cancer. Recent data shows that the use of GnRH agonists is associated with higher cardiovascular morbidity and mortality and, suggesting the shorter time to testosterone suppression and lack of testosterone surge, GnRH antagonists might be more clinically beneficial.

Purpose:
We aimed to perform a meta-analysis comparing the cardiovascular disease risk between degarelix and gonadotropin-releasing hormone agonists in patients with all stages of prostate cancer.

Methods:
PubMed, Scopus and Web of Science databases were searched for randomized control trials (RCTs) and observational studies assessing the cardiovascular disease risk between degarelix and GnRH agonists in patients with prostate cancer. The outcomes of interest were (1) Cardiovascular Disease Risk, (2) Major Adverse Cardiovascular Events, (3) Stroke, (4) All-Cause Death, (5) Myocardial Infarction, (6) Heart Failure, (7) Arrhythmia, and (8) Hypertension. We computed binary endpoints risk ratio (RR) or hazard ratio (HR) with 95% confidence intervals (CI), which were analyzed using a random-effects model. Heterogeneity was examined with I2 statistics. P values of ≤ 0.05 were considered statistically significant. Statistical analyses were performed using RStudio, version 4.2.3.

Results:
8 RCTs and 7 observational studies were included (123,969 patients; mean age 75 years; 12 months follow-up). Degarelix was associated with a significantly lower incidence of major adverse cardiovascular events (10.30% degarelix vs. 31.01% GnRH agonists; RR 0.59; 95% CI 0.41, 0.84; p = 0.003; I2=84%). Incidence of stroke (1.04% degarelix vs. 2.56% GnRH agonists; RR 0.89; 95% CI 0.56, 1.42; p = 0.62; I2=0%), all-cause mortality (3.15% degarelix vs. 5.24% GnRH agonists; RR 0.64; 95% CI 0.37, 1.13; p = 0.12; I2=41%), hypertension (4.05% degarelix vs. 5.78% GnRH agonists; RR 0.71; 95% CI 0.48, 1.04; p = 0.08; I2=0%), myocardial infarction (HR 1.04; 95% CI 0.59, 1.84; p=0.86; I2=66%), heart failure (HR 0.79; 95% CI 0.38, 1.62; p=0.52; I2=79%) and arrhythmia (4.58% degarelix vs. 10.67% GnRH agonists; RR 0.63; 95% CI 0.28, 1.41; p = 0.86; I2=37%), did not reach a statistically significant difference between groups.

Conclusion:
In patients with prostate cancer, degarelix is associated with a significantly lower incidence of major adverse cardiovascular events.
Abstract 4140562: Cardiopulmonary Measures in Those With Chronic Obstructive Pulmonary Disease: E-Cigarettes vs. Combusted Cigarettes
Authors: Katz Brian , Medina Norman , OConnor Shannon , Coleman Sulamunn , Irvin Charlie , Kaminsky David , Menson Katherine , Gaalema Diann
Published: November 2024

Background:
E-cigarettes may be less harmful than combustible cigarettes, though results from research with objective outcomes are limited. Comparisons of the cardiopulmonary effects of e-cigarettes and combustible cigarettes in controlled settings are necessary.

Aims:
Examine cardiopulmonary effects of combustible cigarettes vs. e-cigarettes using a within-subjects design in individuals with chronic obstructive pulmonary disease (COPD) who smoke.

Hypothesis:
Cardiopulmonary measures will improve following e-cigarette use compared to combustible cigarette use.

Methods:
Twenty-one individuals ≥40 years old who smoke (≥5 cigarettes/day for ≥1 year) while diagnosed with COPD underwent two consecutive randomly ordered 2-week phases: a cigarette phase (usual-brand cigarettes) and nicotine-containing e-cigarette phase (combustible-cigarette abstinence with 3% and/or 5% nicotine tobacco-flavored JUUL available). During the e-cigarette phase, participants earned monetary incentives for CO readings ≤6ppm to promote cigarette abstinence. Pulmonary (spirometry, oscillometry, COPD Assessment Test [CAT], Saint George’s Respiratory Questionnaire for COPD [SGRQ-C]) and cardiac (heart rate, blood pressure) measures were completed at baseline and after each phase. Changes in pulmonary and cardiac measures across assessments were analyzed using a mixed-model repeated-measures ANOVA.

Results:
Fourteen participants (66.66%) maintained cigarette abstinence during the e-ciguarette condition. There were no significant differences in objective (spirometry, oscillometry) or self-reported (CAT, SGRQ-C) by condition. Of the cardiac measures, diastolic blood pressure significantly differed by condition (F(2,40) = 3.87,
p
< 0.05), with higher measures after the completion of the cigarette phase (
p
= 0.02).

Conclusions:
Participants were largely able to conform to the study conditions. However, cardiopulmonary changes were minimal with only diastolic blood pressure differing by condition. Nonetheless, the absence of impairments in pulmonary and cardiac health during this 2-week e-cigarette phase suggests evaluations of longer durations of e-cigarette exposure, with concurrent cigarette abstinence, are warranted to determine the safety of e-cigarettes as a potential replacement for combustible-cigarettes.
Abstract 4140571: High-Sensitivity Troponin Rules Out Risk of Myocardial Infarction and Death at 30 Days in Patients with Moderate and High HEART Score
Authors: Kramer Ethan , Abchee Nicolas , Rezk Rogina , Waples Michelle , Meisel Emily , Allen Brandon , Ruzieh Mohammed
Published: November 2024

Introduction:
The HEART score, developed over 15 years ago, aimed to guide the disposition decision for patients presenting to the emergency department (ED) with chest pain. A main concern for these patients is avoiding a missed myocardial infarction (MI). The original studies to develop the HEART score relied on an older generation of troponin assays, however high-sensitivity troponin assays are now widely used and have greatly enhanced the detection of MI. There is uncertainty in the utility of using the HEART score in the current era.

Question:
Can high-sensitivity troponin assays rule out risk of MI and death in patients with a moderate or high HEART score?

Methods:
We analyzed patients presenting to the University of Florida Shands Hospital, a tertiary medical center, with chest pain, high-sensitivity troponin I levels below the 99th percentile, and moderate or high-risk HEART score; 4-6 and 7+, respectively. Patients were recruited from June 2019 to December 2023. The HEART score was collected prospectively as part of our chest pain registry. We calculated the negative predictive value (NPV) for the outcomes of MI and cardiovascular death or death from an unknown cause at 30 days.

Results:
We included 1329 patients. The average age was 58.9 years and 52.7% were women. High sensitivity troponin I was negative (<6 ng/L) in 892 patients and detectable but less than the 99th percentile (<15 ng/L for women and <20 ng/L for men) in 437 patients. A total of 1222 patients had moderate and 107 patients had high HEART scores. There were two (0.2%) MIs and one (0.1%) death in patients with negative troponin levels and no MI or death in patients with detectable levels below the 99th percentile. The NPV for negative or detectable troponin levels below the 99th percentile for both outcomes combined was 99.8% in the cohort overall, 99.8% in patients with a moderate HEART score, and 100% in patients with a high HEART score (Figure 1).

Conclusion:
In patients with chest pain and a moderate or high HEART score, negative or detectable high-sensitivity troponin levels below the 99th percentile have a high NPV in ruling out MI and death at 30 days. These findings can inform decision making in the ED for chest pain patients.
Abstract 4140605: Challenges in Coronary Angiography Through Radial Artery Access due to Anatomic Variations: A Single-Center Experience
Authors: Harmouch Wissam , Villarreal Rizzo Alan , Thakker Ravi , Abdurrahman Selma , Patel Vishal , Kumar Neha , Farooqi Salman , El Haddad Danielle , Gilani Syed , Khalife Wissam
Published: November 2024

Background:
Radial artery (RA) access has become common in cardiac catheterization due to fewer vascular complications and MACE compared to transfemoral approach (TFA). However, anatomic variations are more profound in the upper-extremity.

Research Question:
What are common anatomic variations encountered during transradial approach (TRA) coronary angiography and what association do they have with adverse outcomes and procedural challenges?

Methods:
We performed a single-center retrospective analysis of 926 patients who underwent coronary angiography through TRA via the right upper-extremity where RA angiogram was performed from 01/2010 to 01/2023. Multivariate logistic regression was utilized to estimate the odds ratio (OR) of the association between anatomic variations and adverse outcomes and procedural challenges.

Results:
A total of 926 patients with a mean age of 59.9 years were studied with 30.4% being female. Common comorbidities were HTN (82.2%), HLD (51.8%), and DM (45%). About 32% of patients had an anatomic variation. Prevalences were 14.4% radial tortuosity, 12% high RA bifurcation, 11.9% M-sign, and 1% RA loops. These patients were older (P<0.001) and more likely to have HLD (P=0.049). They had high odds of high contrast dose (OR 1.73; 95% CI 1.28-2.34, P<0.001), long fluoroscopy time (OR 2.02; 95% CI 1.50-2.73, P<0.001), high radiation exposure (OR 2.47; 95% CI 1.79-3.42, P<0.001), difficulty engaging coronary arteries (OR 2.70; 95% CI 1.94-3.74, P<0.001), and transfer to TFA (OR 4.89; 95% CI 2.36-10.12, P<0.001). Females (OR 2.89; 95% CI 2.01-4.15, P<0.001), small RA size (OR 2.61; 95% CI 1.76-3.86, P<0.001), high RA bifurcation (OR 1.68; 95% CI 1.02-2.75, P=0.04), and M-sign (OR 2.04; 95% CI 1.24-3.35, P=0.005) were associated with RA spasm. Major complications were not significant.

Conclusion:
We found a high prevalence of anatomic variations. They were associated with high odds of adverse outcomes and procedural challenges during TRA coronary angiography.
Abstract 4140616: Proteomic biomarkers are associated with high-risk plaque phenotype and adverse events in the PROMISE trial
Authors: Karpurapu Anish , Kwee Lydia , de Calvacamp Caroline , Zhao Elizabeth , Nasir Khurram , Foldyna Borek , Douglas Pamela , Shah Svati
Published: November 2024

Introduction:
Cardiovascular events occur in patients without obstructive coronary artery disease (oCAD), indicating a need for better risk stratification tools. CT angiography (CTA)-based high-risk plaque (HRP) characteristics predict such events effectively but are not widely available. We performed comprehensive proteomics profiling in the PROMISE trial to identify biomarkers associated with HRP, oCAD, and major adverse cardiovascular events (MACE).

Methods:
The PROMISE trial randomized patients with stable chest pain to CTA vs. stress testing. Proteomic profiling (Olink, 524 proteins) was performed on 1724 participants with CTA and biospecimens. A high-risk composite phenotype (HRCP) was defined as presence of oCAD (≥50% stenosis in any major vessel), Leaman score >5, coronary artery calcium score ≥400, or HRP features on CTA. Individual proteins were tested for association with HRCP (false discovery rate-adjusted p-value [q] <5%), followed by pathway analyses, association testing with MACE, and Mendelian randomization. K-means phenoclustering was used to identify clinical clusters. Proteins were then tested for association with the clusters.

Results:
Thirty-seven proteins were significantly associated with HRCP in models adjusted for clinical covariables. These included GDF-15 (OR [95% CI]=1.4 [1.1-1.7], p=0.01), ACE2 (OR=1.4 [1.1-1.7], p=0.002), and LPL (OR=0.7 [0.6-0.9], p=0.01); proteins represented biologic pathways of metabolic regulation, inflammation, and protein degradation. Phenoclustering identified three patient subgroups with varying cardiovascular risk factors; levels of 32/37 proteins varied across the clusters. Seven of the 37 proteins were associated with MACE, including LPL (HR=0.5 [0.4-0.8], q=0.003), CTSD (HR=1.9 [1.2-2.9], q=0.009), GDF-15 (HR=1.7 [1.1-2.5], q=0.01), and ACE2 (HR=1.8 [1.3-2.6], q=0.002) with a direction of effect consistent with odds of HRCP. Mendelian randomization analyses suggest a causal role only for CTSD (cathepsin D) in CAD.

Conclusion:
This study identified novel biomarkers associated with high-risk CAD phenotypes and adverse outcomes in the PROMISE trial, most of which also differentiated clinical phenoclusters, suggesting they report on molecular heterogeneity underlying clinical differences in patients at risk for CAD. These findings highlight potential biomarkers with clinical utility for improved risk stratification and elucidate one potential therapeutic target (CTSD) in the causal pathway of CAD events.
Abstract 4140617: SGLT-2 Inhibitors and Atrial Fibrillation Incidence Following Heart Failure Hospitalization in a Diabetic Population
Authors: Fretz Thomas , Ilonze Onyedika , Tanawuttiwat Tanyanan , Das Mithilesh
Published: November 2024

Introduction:
The development of atrial fibrillation (AF) in patients with heart failure (HF) is associated with increased morbidity and mortality. Initially developed as a diabetic medication, SGLT-2 inhibitors have been shown to improve hospitalization rates and mortality in patients with heart failure. Meta-analyses of large prospective trials suggest SGLT-2 inhibitors prevent the incidence and burden of atrial fibrillation, though this specific question has not been specifically addressed by prospective trials.

Hypothesis:
SGLT-2 inhibitors reduce the incidence of atrial fibrillation in patients who have diabetes following heart failure hospitalization.

Aims:
The goal of this study was to evaluate the effect of SGLT-2 inhibitors on the incidence of atrial fibrillation in a diabetic population following hospitalization for heart failure.

Methods:
The study included consecutive patients with diabetes admitted to an academic tertiary care center over a 3 year time period with a primary diagnosis of heart failure exacerbation and without prior diagnosis of AF. The primary outcome is incidence of new AF within 12 months after hospitalization. Demographic, comorbidity, echocardiographic data, and medications were obtained from the medical record. Cox-regression analysis was performed to identify the predictors of AF following HF hospitalization.

Results:
A total of 2,300 patients were included, 24.3% of whom were prescribed SGLT-2 inhibitors. Of those included, 499 (21.7%) have HFrEF, 309 (13.4%) have HFmrEF, and 1492 (64.9%) have HFpEF. The use of SGLT-2 inhibitor demonstrated a statistically significant association with lower incidence in AF at one year following heart failure hospitalization. Patients on an SGLT-2 inhibitor had a AF incidence of 13.2% compared to an incidence of 20.2% in those not taking an SGLT-2 inhibitor. This difference was found to be statistically significant (
p<0.001; RR 0.62; 95% CI: 0.48-0.80
).

Conclusion:
The use of SGLT-2 inhibitors is associated with a statistically significant reduction in new-onset AF at one year following hospitalization for heart failure in patients with diabetes.
Abstract 4140622: Systemic hypotension triggered by stretching of shoulder and upper back muscles: A possible basis for ‘stretch-syncope’ in humans
Authors: Kosmopoulos Marinos , Reyes Jorge , Patel Sima , Simpson Hannah , Sutton Richard , van Dijk Jan , Thijs Roland , Benditt David
Published: November 2024

Background:
Stretch induced syncope (SIS) is a well-known but rare condition of uncertain pathophysiology. Proposed but unproven mechanisms include Valsalva-like straining, transient vertebral artery occlusion, carotid baroreceptor activation or a combination of these. We hypothesized that shoulder and upper back stretching, possibly acting through skeletal muscle mechanoreceptors, may trigger a hypotensive response, similar to that induced by stretch of other large skeletal muscles (e.g., legs and forearms), but opposite in direction.

Objective:
This study evaluated the impact of shoulder and upper back stretch on autonomic and hemodynamic findings in otherwise healthy patients with SIS by history compared to controls being evaluated for syncope or near syncope unrelated to stretch.

Methods:
The study comprised 18 otherwise healthy patients presenting for hemodynamic and autonomic evaluation of syncope or near-syncope. None had evidence of underlying structural cardiovascular disease or abnormal neurological findings on exam.

Autonomic evaluation was performed in included i) heart rate (HR) and blood pressure (BP) responses during active standing (AS), ii) Valsalva maneuver, and iii) respiratory sinus arrhythmia. Suspected SIS patients also underwent carotid sinus massage while seated. In addition, seated patients were instructed to undertake active extension of the neck and shoulders for approximately 10 seconds while keeping their forearms still and breathing normally. HR and systolic and mean BPs were recorded using beat-by-beat non-invasive plethysmography.

Results:
The patient population comprised 5/18 patients with a history suggesting SIS and 13/18 controls. With stretching, both SIS and control patients exhibited decreased systolic and mean arterial pressure (MAP), and increased HR. Further, SIS patients had a greater decrease in SBP and MAP during stretch than controls (p=0.021 and 0.029). Syncope or near-syncope developed in four SIS patients (80%) during stretch while no control experienced syncope or near-syncope (p<0.001).

Conclusion:
Stretching of upper body musculature induces a previously unrecognized transient hypotensive response within humans. SIS patients manifesting more marked hypotension than controls. Thus, vasodepression, possibly initiated by stretch-induced mechanoreceptor activation within upper back and neck muscles, offers a basis for systemic hypotension in stretch-induced syncope.
Abstract 4140648: Wake up call for the need of standardized medical management for Myocardial Infarction with non-obstructive coronary arteries (MINOCA): A Meta-analysis
Authors: Mohan Ayushi , Rajotia Arush , Bagheri Sina , Bhattar Keshav , Reddy Srivaibhav , Reddy Krishna Theja , Ho Andrew
Published: November 2024

Introduction:
Myocardial Infarction with non-obstructive coronary arteries (MINOCA) falls on one end of the spectrum of acute myocardial infarction (AMI) and obstructive coronary disease (OCD) falls on the other end. The pathophysiologic mechanisms behind MINOCA include microvascular dysfunction, coronary spasm and plaque rupture without significant luminal obstruction. Despite its apparent benign anatomical findings, it is associated with major adverse cardiovascular events (MACE). Therapeutic strategies to mitigate the risk of MACE are less defined for MINOCA as compared to OCD. Due to various pathological mechanisms behind MINOCA, it is not certain that the classical medical strategies are optimal therefore there is a dire need for a standardized medical management for this subset of patients.

Method:
Pubmed database was searched using keywords “MINOCA”, “mortality” and “MACE” from 2015 to 2024. All the relevant observational studies were included using PRISMA guidelines. MACE include in-hospital mortality, heart failure, recurrent myocardial infarction (MI) and stroke.

Results:
7 relevant observational studies (N= 579,754) were included in the systematic review. A total of 33,050 patients had MINOCA out of which 5862 (18%) suffered MACE. 4 relevant studies were further assessed to check the specific risk of recurrent MI and stroke in MINOCA population. Out of 30,491 MINOCA patients 1095 (3.6%) had recurrent MI and 742 (2.4%) suffered from stroke. The pooled analysis revealed a statistically significant association between MACE and MINOCA patients (Odds ratio [OR] = 1.44, 95% CI: 1.03 - 2.02, p = 0.03). Further sub-analysis also revealed a statistically significant association between recurrent MI (Odds ratio [OR] = 2.05, 95% CI: 1.15 - 3.68, p = 0.02) and MINOCA. Pooled sub-analysis for association between stroke and MINOCA population was also statistically significant. (Odds ratio [OR] = 0.87, 95% CI: 0.81 - 0.94, p = 0.00)

Conclusion:
Although MINOCA patients experience fewer MACE as compared to OCD patients, they require a specific standardized medical management to address their pathophysiology and its associated substantial cardiovascular risk. Further research is required to prove these results and to elucidate optimal therapies to improve outcome of patients with MINOCA.
Abstract 4140660: Clinical Outcomes of GLP-1 RA in Heart Failure with CKD patients: A TriNetX Based Global Study
Authors: Hanif Muhammad , Jaiswal Vikash , Bhandari Jenish , Ali Junaid , Devakumar Sahana , Ishaq Muhammad , Sundas FNU , Yousaf Hamza , Khan Arshan , Islam Sabeeh , Singh Sumi , Ochani Rohan Kumar , Yasmin Farah , Jha Mayank , Chaudhuri Debanik
Published: November 2024

Background:
Glucagon-like peptide-1 (GLP-1) receptor agonists are well-established glucose-lowering medications for the treatment of type 2 diabetes, and are cardio-protective by reducing the incidence of major adverse cardiovascular events (MACE). However, there is limited data available with conflicting results on safety of GLP-1RAs among patients with heart failure (HF) with chronic kidney disease (CKD) patients.

Objective:
To assess the potential therapeutic benefits of GLP-1RAs in HF patients with CKD.

Method:
We queried the TriNetX Global Collaborative Network for adult’s patients with heart failure and chronic kidney disease (CKD) from January 2005 to April 2023, and created two cohorts: one with heart failure and CKD on GLP-1 RAs and the other one heart failure and CKD on placebo as control cohort. Both the cohorts were followed for 12 months. We used the ICD-10-CM codes to identify comorbidities, and RxNorm for prescription. Demographics and laboratory values were reported by TriNetX. Propensity score matched analysis (PSM) was done for age, gender, race, hypertension, diabetes mellitus, chronic kidney disease, smoking status, hemoglobin level, LDL level, left ventricular ejection fraction and various drugs including ACEi, ARBi, beta blockers, aldosterone receptor antagonists, SGLT-2 inhibitors and statins. Primary outcome was all-cause mortality (ACM) while secondary outcomes were acute myocardial infarction (AMI), major adverse cardiovascular outcome (MACE) (Composite of ACM, AMI, and ischemic stroke), hemorrhagic stroke, and ischemic stroke.

Resultsxs:
Amongst the 1,05,414 patients (52, 707 patients in each group), the mean age of patients were 68.8 and 68.0 in GLP-1 RAs and control cohort respectively. PSM analysis showed that at one year of follow-up, GLP-1 RAs in heart failure with CKD patients was associated with significantly lower risk of primary outcome i.e., ACM (RR 0.400, 95% CI: 0.384-0.417) as compared with control. Heart failure with CKD patients on GLP-1 RAs were also associated with significantly reduced MACE (RR 0.536, 95% CI: 0.515-0.557), AMI (RR 0.633, 95% CI: 0.597-0.671), ischemic stroke (RR 0.760, 95% CI 0.712-0.811) and hemorrhagic stroke (RR 0.493, 95% CI 0.423-0.575) as compared with control.

Conclusion:
GLP-1 RAs use among patients with HF and CKD were associated with significant reduction in MACE, ACM, and stroke.
Abstract 4140669: Leveraging Large Language Models (LLMs) For Randomized Clinical Trial Summarization
Authors: Mangla Anjali , Thangaraj Phyllis , Khera Rohan
Published: November 2024

Background:
With widespread scientific misinformation, access to primary literature, such as randomized clinical trials (RCTs), can empower patients in their decision-making about their health. However, scientific publications for RCTs – the bedrock of evidence-based cardiovascular care – are not written in accessible language for patients. We hypothesized that large language models (LLMs) could appropriately summarize RCTs into understandable language based on evaluation objective tools, enhancing patient-provider communication and informed consent.

Methods:
From the 3 major medical journals, we extracted 60 RCTs published between January and December 2023. Of these RCTs, 28% were cardiovascular. Each study’s abstract was the used as the reference text or the publicly available summary. Using the chat interface of GPT4, (1) we prompted it to summarize the complete articles to maximize patient understandability (Prompt 1), and (2) prompted it to score 100% on the Patient Education Materials Assessment Tool (PEMAT), a scoring system for evaluating health literacy developed by the AHRQ (Prompt 2). Two evaluators scored original article abstracts, Prompt 1 and Prompt 2. The 8 relevant PEMAT Understandability Scale Questions scored 0 (not present) or 1 (present), with a mean of 0.7 representing the accepted threshold for understandability [A].

Results:
The abstracts scored a 0.5 (IQR 0.4, 0.6) on PEMAT, with 8.3% scoring above 0.7, with significant differences across the 3 journals [B]. Prompt 1 scored a 0.9 (IQR 0.8, 1.0), with 83.3% scoring above 0.7, and Prompt 2 scored a 1.0 (0.9, 1.0) and higher than Prompt 1 (p<.001), with 100% scoring above 0.7 [B]. Both Prompts scored higher than the respective abstracts (p<.001). These patterns were consistent across cardiovascular and non-cardiovascular RCTs. The domains where there were most substantial improvements from abstracts to Prompts 1 and 2 included the degree of distracting information, use of everyday language, explanation of medical terms, and of numbers, and without the need to do calculations.

Conclusion:
LLMs that are primed to align summaries with levels of health literacy, and especially with objective scores, can enable patients to have accessible and reliable information by summarizing primary clinical literature in language understandable to patients.
Abstract 4140674: Combined left atrial appendage occlusion and catheter ablation in patients with atrial fibrillation: a systematic review and meta-analysis
Authors: R.C. Clemente Mariana , Navalha Denilsa , Bittar Vinicius , Costa Thomaz , Prusch Fernandes Gabriel , Silva Livia
Published: November 2024

Background:
Left atrial appendage occlusion (LAAO) and catheter ablation (CA) for atrial fibrillation (AF) have been increasingly performed in combination. However, the effects of this combined procedure remain unknown.

Hypothesis:
Combined LAAO and CA improves outcomes of patients with AF relative to isolated LAAO.

Aims:
To compare the outcomes of combined LAAO and CA with isolated LAAO in patients with AF.

Methods:
PubMed, Embase, and Cochrane Library were systematically searched from inception to March 2024 to identify studies comparing combined LAAO and CA versus isolated LAAO. We pooled odds ratios (OR) with 95% confidence intervals (CI) for binary endpoints. Statistical analyses were performed using R software version 4.3.1.

Results:
We included eight retrospective studies comprising 51,802 patients, of whom 1,375 (2.6%) received the combined procedure, and 29,696 (57.3%) were men. Mean age of patients ranged from 63.6 to 71.4 years. Follow-up ranged from 1 to 37.6 months. Additionally, 626 (1.2%) patients had paroxysmal AF and 757 (1.4%) had persistent AF. There were no significant differences between the combined procedure and LAAO alone in terms of major bleeding (OR 0.55; 95% CI 0.09 to 3.41; p=0.52; Figure 1A), stroke (OR 1.03; 95% CI 0.35 to 3.00; p=0.96; Figure 1B), or pericardial effusion (OR 1.18; 95% CI 0.60 to 2.33; p=0.63; Figure 1C).

Conclusion:
In this meta-analysis, there were no significant differences in major bleeding, stroke, or pericardial effusion when comparing combined LAAO and CA with isolated LAAO.
Abstract 4140693: Gender, Racial, and Ethnic Variations in the Disposition of Chest Pain Patients in the Emergency Department
Authors: Waples Michelle , Kramer Ethan , Rezk Rogina , Meisel Emily , Abchee Nicolas , Allen Brandon , Ruzieh Mohammed
Published: November 2024

Introduction:
Patients presenting to the emergency department (ED) with chest pain are frequently admitted to inpatient or observation units. We sought to assess gender, racial, and ethnic variations in the care of chest pain patients presenting to the ED.

Methods:
A retrospective chart review of patients presenting to UF Health Shands ED from 6/2019–12/2023 with chest pain was conducted. We included patients with high-sensitivity troponin I levels below the 99
th
percentile (<15 ng/L for women and <20 ng/L for men) and moderate or high HEART score (4-6 and 7+, respectively). HEART score was determined at initial presentation. We analyzed the type of ED dispositions based on gender, race, and ethnicity. Negative predictive value (NPV) was calculated for the composite outcome of myocardial infarction (MI) and cardiovascular death or death from unknown cause within 30 days.

Results:
We included 1329 patients (52.7% women). Black represented 24.8% of patients, American Indian or Alaska Native 0.4%, Asian or Pacific Islander 1.1%, and white 67.7%. Hispanic or Latino represented 6.9% of patients. The proportion of patients admitted to the hospital or observation unit was lower in women than men (25.7% vs 30.7%; p=0.0002). Black patients were less likely to be admitted or observed compared to white (22.7% vs 30.3%; p= 0.006). Similarly, Hispanic or Latino patients were less likely to be admitted to the hospital or observation unit (20.7% vs 28.6%; p=0.04). There were 2 MIs and 1 death in the cohort, with 2 of these events being women but no events in black or Hispanic or Latino patients. The NPV for troponin levels below the 99
th
percentile for our composite outcome was 99.8% in the cohort overall, 99.7% in women, 99.8% in men, 99.7% for white, 100% for black, and 100% for Hispanic or Latino patients.

Conclusions:
Among patients with chest pain presenting to the ED with moderate or high HEART score but troponin levels below the 99
th
percentile, women, black, and Hispanic or Latino patients were less likely to be admitted to the hospital or observation unit. Despite these disparities, outcomes at 30 days were similar compared to other groups, and high-sensitivity troponin performed well across all groups.
Abstract 4140703: CXCL10 and IFN-γ Mediate Myocardial Injury Post-COVID-19 mRNA Vaccination
Authors: Nishiga Masataka , Cao Xu , Manhas Amit , Caudal Arianne , Mondejar-Parreno Gema , Zhao Shane , Jahng James , Wang Mingqiang , Utz Pj , Nadeau Kari , Wu Joseph
Published: November 2024

Background:
The mRNA vaccines against COVID-19 are highly effective but have been associated with a rare non-infective form of myocarditis, particularly in young males after receiving the second dose. Understanding the mediators of this adverse effect is crucial to enhance the safety of future mRNA vaccines.

Hypothesis:
Myocardial injury following COVID-19 mRNA vaccination is mediated by overproduced cytokines, and estrogens have a protective effect on this adverse effect.

Approach:
Candidate cytokine mediators were identified through analysis of proteomics data from plasma samples of vaccinated individuals. Human iPSC-derived macrophages and cardiomyocytes were used to model cytokine-induced effects. An in vivo mouse model of cytokine-induced myocardial injury was employed to assess the impact of the cytokine cocktail and estrogens.

Results:
CXCL10 and IFN-γ were consistently upregulated in vaccinated individuals on day 1 and further elevated in patients with myocarditis following mRNA vaccination. Consistently, iPSC-derived macrophages exposed to COVID-19 mRNA vaccines produced these cytokines. Next, iPSC-derived cardiomyocytes exposed to these cytokines showed impaired contractility, arrhythmogenicity, and pro-inflammatory gene expression. The phytoestrogen genistein mitigated these effects in vitro, reducing cytokine-induced proteasomal degradation of cardiac proteins and preserving contractile function. In vivo, genistein significantly decreased cardiac injury markers and immune cell infiltration in a mouse model of cytokine-induced myocardial injury.

Conclusion:
CXCL10 and IFN-γ are key mediators of myocardial injury post-mRNA vaccination. Genistein shows potential as a therapeutic agent to mitigate associated cardiovascular risks.