bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4123639: Tumor Endothelial Marker 1 is Upregulated in Atrial Cardiac Fibroblasts in Atrial Fibrillation and Correlates With Atrial Fibrosis
Authors: Li Yi-Heng , HU YUNING , Huang Ting-Chun , Huang Mu-Shiang , Chung Hsing-Chun
Published: November 2024

Background:
Tumor endothelial marker 1 (TEM1 or CD248) is a transmembrane protein found in activated mesenchymal cells during embryo development. Its expression level becomes very low or undetectable in adult tissue. Re-expression of TEM1 in fibroblasts has been reported in hepatic, renal, and pulmonary fibrosis. We evaluated atrial TEM1 expression in atrial fibrillation (AF) and its relation with atrial fibrosis.

Methods and Results:
All data were presented as mean±standard error. Left atrial (LA) tissues were collected from 30 patients (pts) (mean age 64.0±1.6 yrs, male 76.7%) with AF underwent cardiac surgery (mitral and/or tricuspid valve surgery 96.7%) and maze procedure with LA appendage excision. Immunofluorescence (IF) staining showed TEM1 expressed in atrial cardiac fibroblasts (CFs) in the LA tissue of AF pts, but not in normal LA tissue (US Biomax). Primary human CFs were directly isolated from the LA tissue. IF staining showed TEM1 expression in the isolated CFs from AF pts but not in normal human CFs (ScienCell). Western blot could detect TEM1 expression in the LA tissues of all 30 AF pts. Sirius Red staining was used to visualize collagen and atrial fibrosis was quantified using a pixel-based method (Adobe Photoshop) by calculating the total numbers of red pixels and the percentage (%) of red pixels to total pixels. Atrial fibrosis was increased in AF pts compared with normal control (total number of red pixels: 160740±13066 vs. 50863±6357, % of red pixels to total pixels: 11.4±0.8 vs. 3.8±0.2%, all p<0.001). There was a positive correlation between the expression level of TEM1 (ratio of TEM1/actin band density in western blot) with the severity of atrial fibrosis, including the total numbers of red pixels (r = 0.47, p = 0.01) and the % of red pixels to total pixels (r = 0.48, p = 0.01). TEM1 and galectin expression levels had positive correlation (r = 0.60, p < 0.01). There were no correlations of atrial TEM1 expression with the LA diameter and CHA2DS2-VASc score. In vitro study showed TEM1 knockdown in cultured CFs with siRNA reduced cell proliferation (scrambled- vs TEM1-siRNA, BrdU absorbance: 1.84±0.05 vs 1.50±0.07, p<0.05), increased starvation-induced cell apoptosis (cell death ELISA absorbance: 0.69±0.11 vs 2.88±0.05, p<0.05) and decreased cell migration.

Conclusions:
There is increased TEM1 expression in atrial CFs in AF and its expression level is associated with atrial fibrosis. TEM1 expression changes the cell behaviors of CFs.
Abstract 4124966: Trends and Gender Differences in Stroke Mortality Rates Among Patients with Atrial Fibrillation/Flutter from 1999 to 2020
Authors: Motairek Issam , Tabaja Chadi , Al-Dalakta Astefanos , El Hajjar Abdel Hadi , Badwan Osamah , Besir Besir , Farwati Medhat , Hussein Ayman , Younis Arwa , Taigen Tyler , Rickard John , Bhargava Mandeep , Kanj Mohamed , Baranowski Bryan , Nakhla Shady , Santangeli Pasquale , Chung Mina , Saliba Walid , Wazni Oussama
Published: November 2024

Background:
Atrial fibrillation (AFib) and atrial flutter (AFL) are common arrhythmias associated with increased stroke risk. This study examines stroke mortality trends and gender differences among AFib/AFL patients in the United States over a 22-year period.

Research Question:
Do stroke mortality rates among patients with AFib/AFL show significant trends and gender differences from 1999 to 2020?

Aims:
The primary aim is to analyze trends in crude and age-adjusted stroke mortality rates and determine gender-specific differences over the 22-year period.

Methods:
We conducted a retrospective analysis using CDC multiple causes of death files from 1999 to 2020. Stroke deaths (ICD-10 codes I60-I69) with AFib/AFL (ICD-10 code I48) as contributory factors were identified. Crude and age-adjusted mortality rates were calculated annually. Joinpoint regression calculated annual percentage change (APC) and assessed trend significance (p < 0.05). Poisson regression was used for rate comparisons. Gender-specific trends highlighted differences between males and females.

Results:
The analysis included 204,127 stroke deaths with AFib/AFL. Both crude and age-adjusted mortality rates increased. The crude mortality rate rose from 3.3 per 100,000 in 1999 to 4.9 per 100,000 in 2020, APC 1.8% (p < 0.01). The age-adjusted rate increased from 3.4 to 4.0 per 100,000, APC 1.2% (p < 0.01). Females had higher crude mortality rates, increasing from 4.3 to 5.5 per 100,000, APC 1.3% (p < 0.01), while males rose from 2.3 to 4.2 per 100,000, APC 2.2% (p < 0.01). Age-adjusted rates: females increased from 3.4 to 3.9 per 100,000, APC 0.8% (p < 0.01), and males from 3.3 to 4.2 per 100,000, APC 1.6% (p < 0.01). Poisson regression indicated these differences were significant (p < 0.05). Age adjustment narrowed gender disparity.

Conclusion:
Increasing stroke mortality rates among AFib/AFL patients highlight a growing public health concern in the United States. Females have higher crude stroke mortality rates than males, but age adjustment reveals a more balanced trend. More work is needed to understand influencing factors, including anticoagulation rates, healthcare access, and AFib/AFL management strategies.
Abstract 4124974: Small delays in door-to-balloon time for patients presenting with STEMI do not impact mortality: a quasi-experimental study
Authors: Oseran Andrew , Almarzooq Zaid , Rymer Jennifer , Brothers Leo , Wojdyla Daniel , Kaltenbach Lisa , Yeh Robert
Published: November 2024

Introduction:
Observational studies have consistently demonstrated a strong association between longer door-to-balloon (DTB) times and increased mortality in patients presenting with ST-elevation myocardial infarction (STEMI). However, the extent to which this association is attributable to unmeasured differences between patients with different DTB times (i.e., confounding), as opposed to a causal impact of longer DTBs is unclear.

Aim:
In this study, we exploit a natural experiment using an instrumental variable (IV) approach based on weekday vs weekend presentation to evaluate whether incremental delays in DTB times have a causal effect on patient outcomes.

Methods:
We performed a retrospective analysis of patients undergoing immediate percutaneous coronary intervention (PCI) for STEMI in the CathPCI Registry from 1/2010 to 12/2021 at 1,422 sites. Time of presentation with STEMI (weekday daytime vs weekend daytime) was used as an IV to address potential confounding. A 2-stage IV analysis was used. In-hospital all-cause mortality was the primary outcome.

Results:
A total of 447,355 patients presented with STEMI during the study period. The average difference in weekend (N=125,787) minus weekday (N=321,568) daytime DTB times was 10.5 minutes. Patient, procedural, and hospital characteristics were well balanced between groups. Overall, in-hospital mortality was 3.5%. In the IV analysis, delays in DTB time were not associated with increased odds of in-hospital mortality (OR 0.99, 95% CI 0.95 to 1.03, P = 0.70). This null association was also observed when limited to hospitals with larger differences (19.5 minutes) between weekend and weekday DTB time (OR 1.00, 95% CI 0.96 to 1.03, P = 0.85) and among patients predicted to have the longest (mean 70.8 minutes) DTB times (OR 1.00, 95% CI 0.94 to 1.07, P = 0.96).

Conclusions:
Contrary to prior findings, incremental delays in DTB time for patients presenting with STEMI are not associated with increased in-hospital mortality when analyzed using quasi-experimental methods less likely to be influenced by unmeasured confounding. Efforts to further reduce DTB times in patients presenting to hospitals with STEMI are unlikely to improve outcomes. In the current era, policies intended to incentivize better care for STEMI patients should prioritize other measures of quality beyond DTB.
Abstract 4134320: Integrated safety and tolerability of mavacamten treatment over 5 years in patients with obstructive hypertrophic cardiomyopathy
Authors: Owens Anjali , Barriales-Villa Roberto , Desai Milind , Garcia-Pavia Pablo , Hagege Albert , olivotto iacopo , Wojakowski Wojtek , Afsari Sonia , Balaratnam Ganesh , Chen Yu Mao , Wang Andrew
Published: November 2024

Background:
Mavacamten, a cardiac myosin inhibitor, is approved across 5 continents for the treatment of obstructive hypertrophic cardiomyopathy (HCM). Long-term data of mavacamten are available from multiple studies, providing the opportunity to further understand mavacamten long term safety, including adverse events (AEs) of clinical interest.

Aim:
To present integrated safety data of patients who received mavacamten treatment for obstructive HCM across 5 studies.

Methods:
The pooled population included all patients who received ≥1 dose of mavacamten in PIONEER-HCM, PIONEER-Open Label Extension (data cut-off: May 31, 2022), EXPLORER-HCM, MAVA-Long-Term Extension (EXPLORER cohort; data cut-off: August 31, 2023) and VALOR-HCM including long-term extension (data cut-off: November 11, 2022).

Results:
The population consisted of 368 patients (mean [SD] age: 59.4 [12.2] years; male: 57.1%; White: 90.8%), including 350 patients who continued onto an extension study after completing a parent study. The majority of patients (57.6%) had a cumulative time on study of ≥3 years. Forty (10.9%) patients permanently discontinued treatment (13 due to AEs). In total, 20.7% of patients had a treatment emergent AE (TEAE) of Grade ≥3 and 14.7% had a TEAE leading to drug interruption. Overall, 4.3% of patients had drug-related serious TEAEs and 1.6% had a TEAE leading to death. The cumulative exposure adjusted incidence rates (EAIR) of all TEAEs, including AEs of clinical interest (atrial fibrillation [AF], ejection fraction [EF] decreased and heart failure [HF]), decreased as exposure increased over time, from 347.1/100 patient-years (P-Y) at Week 60 (~year 1) to 271.8/100 P-Y at Week 252 (~year 5). The EAIR of AF decreased over time from 13.3/100 P-Y at Week 60 (~year 1) to 6.2/100 P-Y at Week 252 (~year 5) (
Figure
). The EAIR for EF decreased and HF also decreased over time (
Figure
).

Conclusions:
This integrated analysis of all patients with obstructive HCM treated with mavacamten across the 5 clinical studies over 5 years demonstrated that mavacamten treatment is generally well tolerated and that the EAIRs of selected TEAEs of clinical interest (AF, EF decreased and HF) decreased as exposure increased over time.
Abstract 4134327: Efficacy and safety of aprocitentan in patients with resistant hypertension receiving at least 4 antihypertensive medications including beta (β) blockers
Authors: Weber Michael , Bakris George , Flack John , Narkiewicz Krzysztof , Sassi-Sayadi Mouna , Schlaich Markus , Wang Jiguang , Ahuja Ajay
Published: November 2024

Background:
Aprocitentan, a dual ET
A
/ET
B
endothelin receptor antagonist, was recently FDA-approved for use in combination with other drugs for the treatment of hypertension not adequately controlled on other antihypertensive drugs. β-blockers are used for the prevention of cardiovascular events and have antihypertensive effects. All subjects in the PRECISION study were hypertensive at screening despite receiving ≥3 antihypertensives, with 63.5% on ≥4 and 16.8% on ≥5 antihypertensives. All were switched to a standardized fixed dose triple combination of amlodipine/valsartan/hydrochlorothiazide; and the 456 patients (62.5% of the 730 total) who were on β-blockers at screening continued throughout the study as well. Of these, 173 (37.9%) had a history of ischemic heart disease and 106 (23.2%) a history of congestive heart failure, vs 52 (19%) and 37 (13.5%) not receiving β-blockers. This preplanned subgroup analysis assessed the efficacy and safety of aprocitentan in patients with resistant hypertension on the triple combination with or without β-blockers.

Methods:
Changes from baseline (BL) in office systolic blood pressure (SBP) and diastolic BP (DBP) were assessed at Week 4, the end of the double-blind treatment phase with aprocitentan 12.5 mg or 25 mg per day or placebo, and at Week 36, at the end of the single-blind aprocitentan 25 mg treatment phase.

Results:
There was no difference in the efficacy of aprocitentan when patients were on a β-blocker or not. In patients on β-blockers, 12.5 mg and 25 mg aprocitentan decreased SBP from BL to Week 4 by mean -14.9 mmHg and -14.9 mmHg, respectively, vs -11.2 mmHg in the placebo group; and in patients without β-blockers by -16.5 mmHg and -14.9 mmHg vs -11.8 mmHg. Similar results were seen at Week 36, as compared with BL for both subgroups, and at Week 4 for DBP (Table 1).

In patients on β-blockers, the incidence of edema/fluid retention at Week 4 was 9.9%, 19.3% and 2.8% in the aprocitentan 12.5 mg, 25 mg and placebo groups, respectively, as compared with 7.6%, 16.7%, and 1.0% in patients without β-blockers. In both subgroups, most events occurred during the first 8 weeks of treatment. The incidence of edema/fluid retention with aprocitentan was comparable with that of the placebo group in both subgroups thereafter.

Conclusions:
Aprocitentan is effective in lowering BP and has a good safety and tolerability profile in patients with resistant hypertension who are taking 4 or more antihypertensive drugs including β-blockers.
Abstract 4135617: Large Scale Proteomics Identifies Circulating Biomarkers Relating Atrial Fibrillation to Heart Failure: the Atherosclerosis Risk in Communities Study
Authors: Giugni Fernando , Lamberson Victoria , Yang Yimin , Chen Lin , Matsushita Kunihiro , Hoogeveen Ron , Ballantyne Christie , Coresh Josef , Yu Bing , Shah Amil
Published: November 2024

Introduction:
There is a bidirectional relationship between atrial fibrillation (AF) and heart failure (HF) risk. Data regarding shared and unique pathways underlying each are limited.

Aims:
Identify plasma proteins associated with both incident AF and HF and determine the extent to which associations with one outcome are conditional on interval occurrence of the other outcome.

Methods:
Among participants in the community-based Atherosclerosis Risk in Communities study free of HF and AF at study visit 5 (2011-2013), we measured 4,955 plasma proteins (SomaScan aptamer-affinity assay). We performed parallel analyses of individual protein associations with incident HF and AF using multivariable Cox regression adjusted for demographic and clinical covariates at Bonferroni significance. We then repeated the analysis for each outcome in models censoring participants with interval occurrence of the other outcome (i.e. incident AF censoring for interval HF, and vice versa). We tested associations of AF-related proteins with echocardiographic and Zio patch measures at Visit 5.

Results:
Among 4,118 participants included, mean age was 75±5 years, 60% were female, and 18% reported Black race. We identified 83 proteins associated with incident HF (n=355 incident events at 7 [IQR 6-8] year follow-up) and 24 with incident AF (n=517 incident events at 8 [7-9] years), of which 10 were associated with both. In models of incident HF censoring for interval AF, 63 (76%) proteins remained significantly associated with HF. In contrast, in the analysis of incident AF censoring for interval HF, only 4 (17%) proteins remained associated with AF, of which 3 were also associated with HF risk (Figure). These 4 AF-related proteins were associated with measures of LV diastolic function (LA volume, E/e’. average), LV mass index, LA function (LA reservoir, LA contraction), and supraventricular ectopy density (all p<0.05).

Conclusion:
Nearly half of proteins reflecting AF risk also associate with HF, greater than 80% of AF-associated proteins are HF-dependent, and even those that are not correlate with measures of LV remodeling and dysfunction. These findings suggest that AF-related mechanisms among older adults are part of a wider HF syndrome.
Abstract 4136905: EF-24, a curcumin analog, reverses interleukin-18-induced miR-30b or miR-342-dependent TRAF3IP2 expression, RECK suppression, and the proinflammatory phenotype of human aortic smooth muscle cells
Authors: Higashi Yusuke , Dashek Ryan , Rector Randy , Delafontaine Patrice , CHANDRASEKAR Bysani
Published: November 2024

Curcumin, a polyphenolic compound derived from the widely used spice
Curcuma longa,
has shown anti-atherosclerotic effects in cultured vascular cells and animal models. We previously reported that the induction of the proinflammatory molecule TRAF3IP2 (TRAF3 Interacting protein 2) or inhibition of the matrix metalloproteinase (MMP) regulator RECK (Reversion Inducing Cysteine Rich Protein with Kazal Motifs) contributes to agonist-induced proinflammatory, pro-oxidant, pro-mitogenic and pro-migratory effects in vascular smooth muscle cells. Here we hypothesized that, EF-24 ((3E,5E)-3,5-bis[2-fluorophenyl (methylene]-4piperidinone), a curcumin analog with better bioavailability and potency, reverses interleukin (IL)-18-induced TRAF3IP2 induction, RECK suppression and the proinflammatory phenotype of primary human aortic smooth muscle cells (ASMC). Exposure to recombinant human IL-18 (10 ng/ml) induced TRAF3IP2 mRNA and protein expression, but markedly suppressed RECK in a time-dependent manner. Further investigations revealed that IL-18 induced miR-30b, but suppressed miR-342, in a p38 MAPK and JNK-dependent manner. While miR-30b inhibitor blunted IL-18-induced TRAF3IP2 expression, miR-30b inhibitor and miR-342 mimic each restored RECK expression. Further, IL-18 induced ASMC migration (Boyden chamber assay) and proliferation (CyQUANT Cell Proliferation assay), and these effects were reversed by TRAF3IP2 knockdown or RECK overexpression. Our results also show that IL-18 induced MMP2 and MMP9 expression and activity, and targeting their expression inhibited IL-18-induced ASMC migration. TRAF3IP2 knockdown or RECK overexpression also reversed IL-18-induced ASMC proinflammatory phenotype switching as evidenced by the enhanced expression of the SMC markers ACTA2 and MYH11, and reduced expression of the proinflammatory markers Galectin 3, Olr1, VCAM, CCL2, IL-6, IL-8, and TNF-α. Importantly, preincubation with EF-24 markedly suppressed IL-18-induced SMC proliferation, MMP expression, migration and the proinflammatory phenotype switching. Together, these results suggest that the curcumin analog EF-24 has therapeutic potential in vascular inflammatory and proliferative diseases, including atherosclerosis, by differentially regulating TRAF3IP2 and RECK in vascular SMC.
Abstract 4136911: Daily Dyadic Symptom Appraisal Dynamics During Care Transitions in Persons with Heart Failure and Their Care Partners
Authors: Bidwell Julie , Ferrer Emilio , Lee Christopher , Cadeiras Martin , Godden Monica , Livingston Marnie , Hinton Ladson
Published: November 2024

Background:
Symptom monitoring after heart failure (HF) hospitalization is a central aspect of patient education. However, appraising symptoms can be difficult for persons with HF (PWHFs), and studies suggest family care partners (CPs) play a key supportive role. The purpose of this study is to examine dyadic HF symptom appraisal dynamics in PWHF-CP dyads during hospital-to-home transitions.

Methods:
We conducted a daily diary study of dyadic symptom appraisal in which PWHFs and CPs were enrolled during a HF hospitalization. Over 5 weeks, both completed daily assessments of the PWHF’s symptoms (HF Somatic Perception Scale, PROMIS Fatigue 4a). Each dyad’s appraisal dynamics were quantified using a set of N of 1 dyadic autoregressive time series models examining total symptoms, hallmark symptoms (dyspnea, edema) and nonspecific symptoms (early/subtle cluster, fatigue). Models were examined for within-dyad dynamics (within-dyad associations on the same day or on a 1-day lag). Patterns in significant dynamics across dyads were narratively described.

Results:
This analysis includes n=14 cohabitating dyads, all partnered. On average, PWHFs and CPs were 69.6±5.4 and 67.4±8.0 years of age. The sample was relatively gender balanced (43% of PWHFs and 64% of CPs identified as female), and primarily identified as non-Hispanic (86% of PWHFs, 93% of CPs) and White (93% of PWHFs, 86% of CPs). Most PWHFs had non-ischemic cardiomyopathy (64%) and were NYHA Class III/IV (86%), with 57% HFrEF (mean EF 37%±17%). Symptom appraisals were highly variable within and across dyads (Fig 1). Most (n=11, 79%) had significant dyadic dynamics, but dynamics across dyads varied by symptom type and time structure (Fig 2).

Conclusions:
The types of symptoms that HF care dyads are able to appraise together and the time structure of appraisals are variable during care transitions. Precision approaches tailored to individual dyads are needed to optimize inclusion of CPs in symptom monitoring interventions.
Abstract 4136930: Plasminogen Activator Urokinase Receptor (PLAUR) Levels are a Predictor of Adverse Cardiovascular Outcomes in the General Population, Independent of High-Sensitive CRP (hs-CRP)
Authors: Sakr Shaimaa , Chuckaree Ishwar , Agusala Veena , Yadalam Adithya , Liu Chang , Gold Matthew , Desai Shivang , Razavi Alexander , Jain Vardhmaan , Quyyumi Arshed
Published: November 2024

Background:
The gene Plasminogen Activator Urokinase Receptor (PLAUR) encodes the urokinase plasminogen activator surface receptor (uPAR), which upon cleavage releases Soluble Urokinase Plasminogen Activator Receptor (suPAR). SuPAR has emerged as a novel biomarker of inflammation and immunity and is associated with adverse cardiovascular events, particularly coronary artery disease (CAD), regardless of hs-CRP levels, a well-established inflammatory biomarker. However, whether the PLAUR gene predicts adverse cardiovascular events remains uncertain.

Methods:
We investigated the relationship between PLAUR levels, measured via Olink Immunoassay, in 40,790 individuals from the UK Biobank, and the occurrence of adverse cardiovascular events such as myocardial infarction (MI), as well as all-cause and cardiovascular mortality. Our analysis involved the use of Cox and Fine and Gray proportional hazards models, adjusting for age, sex, race, HDL, LDL, triglyceride levels, BMI, prevalence of hypertension (HTN), prevalence of type 2 diabetes (T2D), smoking history, and use of blood pressure and cholesterol medications.

Main Outcomes:
The primary outcome was a composite outcome of cardiovascular mortality and MI and the secondary outcome was all-cause mortality.

Results:
The mean (SD) age was 58 (8) years, 45% men and 94% white. During a median follow-up of 14 (interquartile range 12.3 – 15) years, 7.9% of the population had an MI, 2.7% suffered cardiovascular death, 9.5% all-cause mortality. After adjusting for aforementioned demographic and clinical factors, as well as medication usage, each standard deviation increase in PLAUR levels was associated with a heightened risk of incident non-fatal MI and cardiovascular (CV) death, with a hazard ratio (HR) of 2.31 (95% CI 2.00-2.45), and all-cause mortality, with an HR of 3.81 (95% CI 3.48-4.18). Even after further adjustment for hs-CRP levels, PLAUR levels remained predictive of non-fatal MI and CV death (HR 2.03, 95% CI 1.83-2.26) and all-cause mortality (HR 3.43, 95% CI 3.12-3.77). Furthermore, in a fully adjusted Cox regression model, a significant interaction between PLAUR levels and sex (p = 0.0003) was observed in predicting the primary outcome. The interaction was found to have a stronger predictive value in females compared to males.

Conclusion:
PLAUR levels are a strong predictor of adverse cardiovascular outcomes in the general population, independent of traditional risk factors and inflammation.
Abstract 4136938: Autonomous Personalized Dynamic ECG Analysis Predicts 1-hour Incidence of Sudden Cardiac Arrest
Authors: Hazra Debapriya , Jones Steven , Dey Swati , DeMazumder Deeptankar
Published: November 2024

Background:
Sudden cardiac arrest (SCA) is a leading cause of death in the USA. Defibrillators prevent SCA by delivering shocks for sustained ventricular tachyarrhythmias (VT). However, current clinical methods for predicting SCA are limited. We have shown that distinct nonlinear fluctuation patterns “hidden” within normal-appearing ECG waveforms have unique prognostic value.

Hypothesis:
Autonomous personalized dynamic ECG analysis predicts the 1-hour incidence of SCA.

Methods:
In an established pressure-overload model that exhibits key features of human VT and SCA (e.g., cardiac restitution properties), 30% of 37 freely ambulating animals had spontaneous SCA in 4 weeks. The exposures included a rolling 1-hour window of time, frequency and nonlinear domain measures of heart rate and QT time series during sinus rhythm, and EntropyX
QT
, a higher-dimensional machine learning-based nonlinear measure of cardiac repolarization dynamics.

Results:
In multivariate analyses, the major independent predictors of 1-hour incidence of SCA were (1) high EntropyX
QT
; (2) high parasympathetic tone, as indexed by the high-frequency component of the heart rate power spectral density; and (3) the degree of coupling between RR and QT intervals. The baseline values of EntropyX
QT
and parasympathetic tone increased by 3.6-fold and 46.5-fold, respectively, during the hour preceding SCA. The adjusted ROC curve area was > 89%.

Conclusion:
Continuous autonomous analysis of cardiac repolarization and autonomic dynamics strongly and independently predicts the subacute incidence of SCA. Incorporation of these measures into current strategies of SCA risk stratification has potential to save many lives and warrants further evaluation.
Abstract 4136952: The Clinical Importance of Arrhythmia Notifications During Use of Wearable Cardioverter Defibrillator
Authors: Techiryan George , Malinowski Timothy , Rodriguez Laura , Silas Crysta , Bianco Nicole
Published: November 2024

Introduction:
Wearable cardioverter defibrillators (WCDs) record continuous ECG data for the purpose of delivering treatment for lethal arrhythmias, but occasionally capture non-treatable arrhythmias that may be of clinical value. The purpose of this study was to evaluate the usefulness to health care providers (HCPs) of evaluating and reporting these other recorded ECGs and the impact on additional arrhythmia detection and clinical management decisions.

Research Questions:
Do clinicians find arrhythmias identified during routine WCD useful? What arrhythmias are observed? Can the identification of these arrhythmias, validation through ZOLL’s Independent Diagnostic Testing Facility (IDTF) and notification to the provider lead to changes in clinical management?

Methods:
A multi-center, observational study of 52 US HCPs enrolled 474 patients with commercial LifeVest prescriptions and followed them for up to 3 months. All routinely transmitted LifeVest ECG strips (corresponding to Baseline, Patient Initiated, or other automatic event recordings) during this period were analyzed by ECG technicians at the IDTF within ZOLL. These arrhythmias were reported to the HCP who completed a questionnaire assessing the utility (scored 1 to 5) and clinical impact (medication changes, tests, and procedures ordered) of these events.

Results:
At the conclusion of the study, 22% of patients (105/474) monitored had 112 reportable, unique arrhythmia events that were sent to 34 providers who completed questionnaires regarding report utility and clinical management decisions. A significant proportion of reports led to medication changes (40%), additional testing (32%) and procedural interventions (23%). The average usefulness of the reports was 3.63/5 with atrial fibrillation representing the most common arrhythmia, but many variations of ventricular ectopy were also captured which tended to be more clinically useful and impactful.

Conclusions:
WCD patients experience a high burden of actionable arrhythmias. Monitoring and reporting these arrhythmias over the course of normal wear provides additional clinical value to providers. Those arrhythmias that lead to changes to clinical management are the most useful.
Abstract 4136971: Prognostic Value of Late Gadolinium Enhancement to Predict Non-Sustained Ventricular Tachycardia in Patients with Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis
Authors: Siddiqi Ahmed , Maniya Muhammad Talha , bilen ozlem , Abdou Mahmoud , De Cecco Carlo , NAEEM MUHAMMAD
Published: November 2024

Background:
Non-sustained ventricular tachycardia (NSVT) has been shown to be independently associated with sudden cardiac death (SCD) among patients with hypertrophic cardiomyopathy (HCM). There is limited evidence regarding the efficacy of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging to predict the incidence of NSVT.

Aims:
To address this gap in knowledge, our meta-analysis aims to comprehensively evaluate the prognostic value of LGE on cardiac magnetic resonance in predicting the incidence of NSVT in HCM.

Methods:
PubMed, Embase and Cochrane CENTRAL databses were queried from inception until May 2024 for all studies assessing the prognostic value of LGE on CMR in patients with HCM and reported the incidence of NSVT. Data were combined using a random-effects model meta-analysis to determine the pooled sensitivity, specificity and accuracy of LGE in predicting NSVT in patients with HCM. The association between the LGE extent on CMR and NSVT incidence was also assessed, and weighted mean differences (WMDs) were reported with 95% condidence intervals (CIs). Heterogeneity across the studies was evaluated using the Higgins

I
2

statistic.

Results:
A total of twenty studies were included in our analysis. The pooled senstivity, specificity, and accuracy of LGE in predicting the incidence of NSVT among HCM patients was 91.33%, 37.45%, and 52.86%, respectively. Moreover, we saw a significantly greater extent of LGE (5.95%, CI: 3.08-8.81, P<0.0001) in patients who had NSVT, as compared to patients without NSVT (
Figure 1).

Conclusion:
Our meta-analysis underscores the significant prognostic value of LGE as a risk stratification tool on CMR imaging in predicting the incidence of NSVT in patients with HCM, by demonstrating a high sensitivity, and a notable association between the LGE extent and NSVT incidence. Nevertheless, the low to moderate Ispecificity and accuracy underscores the need for additional imaging biomarkers for risk stratification.
Abstract 4136978: Six-month Changes in Lipid Management in the Veterans Affairs Lipid Optimization Reimagined Quality Improvement (VALOR-QI) Program
Authors: Ward Rachel , Wellman Helen , Yel Nedim , Coleman-Lopez Mason , Santos Abigail , DelGrande Jen , Fink Abigail , Colson Kristin , Pan Eddie , Leesch Tharen , Pena David , Congdon Michelle , Burlison Kelly , Djousse Luc , Gaziano John Michael
Published: November 2024

Background:
US Veterans have a high burden of cardiovascular disease (CVD). While cholesterol management is one of the most effective approaches for reducing CVD burden, over two-thirds of Veterans with atherosclerotic cardiovascular disease (ASCVD) are not optimally managed.

Aims:
To evaluate LDL-C monitoring, lipid lowering therapy (LLT) use, and LDL-C levels at baseline and six-months for Veterans in the Veterans Affairs Lipid Optimization Reimagined Quality Improvement (VALOR-QI) Program.

Methods:
VALOR-QI is a national quality improvement collaboration between the US Department of Veterans Affairs and the American Heart Association (AHA) with the goal of improving lipid management among Veterans with ASCVD. To assess and address barriers to achieving optimal lipid levels, Clinical Champions, Health Care Coaches, and participating providers from 50 VA sites work with AHA QI Consultants. Eligible Veterans (those with an ASCVD diagnosis at two outpatient or one inpatient visit or one ASCVD procedure) were considered engaged in VALOR-QI if they had a qualifying appointment with a participating provider during the program. We examined rates of LDL-C monitoring and LLT use at baseline (start of site monitoring) and 6 months after. Among Veterans who were in the program ≥6 months and had >1 LDL-C measure, we investigated percent meeting an LDL-C goal of <70 mg/dL at their first LDL-C (closest to their first visit with priority given to labs within 365 days before their first visit) and follow-up LDL-C (closest to 6 months after entering the program) and mean LDL-C change (paired t-test).

Results:
Six months after starting VALOR-QI, sites had a 41% increase in LDL-C monitoring and a 6% increase in LLT use. Among 29,610 Veterans engaged in the program ≥6 months with at least two lipid labs [mean (SD) age 71.0 (9.3) years, 95% men, 72% white race], the proportion who met the LDL-C goal <70 mg/dL increased from 44% at their first measure to 51% at 6-month follow-up. Among these Veterans, we observed a mean LDL-C decrease of 5.1 mg/dL (95% CI: -5.50, -4.78).

Conclusion:
We observed an increase in lipid monitoring and LLT use and improved LDL-C at 6-month follow-up among US Veterans engaged in VALOR-QI.
Abstract 4136983: Estimating Atrial Fibrillation Rate in Patients Using Artificial Intelligence Referenced to Tissue Action Potentials
Authors: Abad Juan Ricardo Carlos , Anbazhakan Suhaas , Ruiperez-Campillo Samuel , Rodrigo Miguel , Narayan Sanjiv
Published: November 2024

Background:
Ablation by pulmonary vein isolation (PVI) is the most effective approach to treat atrial fibrillation (AF), but 30-40% of patients may not respond. Studies including the CAPLA trial suggest that ablating sites of rapid activation on the posterior left atrial wall or elsewhere may improve success. However, AF rate is rarely calibrated and, since electrograms often include noise or far field activity, may overestimate rate (underestimate cycle length) at many sites.

Hypothesis:
We hypothesized that artificial intelligence (AI) algorithms may more accurately indicate local AF rate, by excluding spurious activations referenced to simultaneous monophasic action potential (MAP) recordings, compared to conventional measurements.

Methods:
We studied N=303 AF patients at ablation (68.2±8.0 years, 17.8% females, 72.9% non-paroxysmal AF). Patients were matched N=229 into development and one quarter (N=74) into hold-out test cohorts. Patients underwent AF mapping using multipolar catheters, and a subset with MAP catheters (MedFact, GmbH). We used the development set to train an AI algorithm to reliably detect AF activations, which we compared in the test cohort to a standard dV/dt approach referenced to adjacent MAPs within 2 mm (N=20 patients) and manually annotated activations (N=64 patients).

Results:
Fig A shows AF in a 66 year old woman, where dV/dt often marked non-physiological activations within repolarization shown in the adjacent MAP. Conversely, the AI system excluded spurious deflections and better correlated with experts (black). In summary, Fig. B shows that AI provided a higher F1 score than dV/dt compared to MAPs (median[IQR]: 0.86 [0.5 - 1] vs. 0.67 [0.40 - 0.73], p<0.01) and experts (0.89 [0.73 - 1] vs. 0.72 [0.60 - 0.89]], p<0.01). Fig C shows that the AI approach better identified AF cycle length (rate; blue) than standard approaches (green) that substantially underestimate cycle length (p<0.05).

Conclusions:
In this large registry, a novel AI-based approach more accurately detected AF rates in clinical electrograms, referenced to experts and action potential recordings, than standard approaches which overestimated rate. AI may improve characterization of AF activity within the atria.
Abstract 4139117: Epidemiology of Patients Undergoing a Rapid Response within the First 24 Hours of Admission at an Urban Academic Center
Authors: Cyr Andrew , Patel Pushpendra , Jnani Jack , Chang Joshua , Jassal Ajay , Leung Christian , Li Shuojohn , Palati Sai , Guntaka Saimanoj , Salam Shafkat , Sood Aditya , Capustin Matthew , Smith Alexander , Weintraub Spencer , Bulsara Kishen , Honigman Jared , Alvarez Villela Miguel , Griffin Matthew , Pierce Matthew
Published: November 2024

Introduction:
A Rapid Response Team (RRT) is an inpatient team that aims to resuscitate deteriorating patients in non-critical care settings and reduce inpatient morbidity and mortality. It is not well understood which patients are likely to deteriorate and need a rapid response (RR) within the first 24 hours of admission.

Research Question:
We sought to identify the most common characteristics for patients who had a RR within 24 hours of admission.

Methods:
We performed a descriptive analysis evaluating 176 patients who had a RR called within 24 hours of admission to North Shore University Hospital from February 2022 to August 2023. Demographic and clinical variables were assessed, including medical history, admitting diagnosis, and indication for RR.

Results:
The median age of the population was 73 years; 92 (52.3%) were male, and 91 (51.7%) were white. The most common comorbidities were hypertension (119, 67.6%), coronary artery disease (51, 28.9%), and heart failure (34, 19.3%). Amongst these patients, acute hypoxic respiratory failure (11.6%) was the most common admission diagnosis followed by sepsis (9.7%) (Table 1). The most common reason for the RR was acute mental status change (26.1%) followed by hypotension (25.0%). Average time spent in the ED prior to admission was 6 hours 41 mins. Intensive care unit (ICU) consultation prior to the RRT occurred in 36 patients (20.5%) and 52 patients (29.5%) were transferred to an ICU while 124 (70.5%) remained on the medicine floors. Regarding hospital utilization, 98 (55.7%) patients were admitted within the last year and 47 (26.7%) patients were hospitalized within the last month. 14 (7.9%) patients had an ICU admission in the past year. 38 (21.5%) patients died during the admission post RR.

Conclusion:
In our cohort of RRs within 24 hours of admission, we observed a high prevalence of cardiac comorbidities and recent hospitalizations, a low prevalence of ICU consults prior to RR, and discordance between admitting diagnoses and reasons for RR. Further studies involving a larger cohort are needed to develop a prediction model for determining patients most at risk of deteriorating after admission and requiring RRs.
Abstract 4139141: Predicted efficacy of inclisiran on cardiovascular outcomes in lower extremity peripheral artery disease: results of the In Silico Sirius study
Authors: Mahe Guillaume , Angoulvant Denis , Amarenco Pierre , Bastien Alexandre , Bechet Emmanuelle , Boccara Franck , Boissel Jean-Pierre , Cariou Bertrand , Courcelles Eulalie , diatchenko Alizee , Filipovics Anne , Kahoul Riad , Granjeon-Noriot Solene , Peyronnet Emmanuel , Portal Lolita , Porte Solene , Wang Yishu , Steg Philippe
Published: November 2024

Introduction:
Symptomatic lower extremity peripheral artery disease (PAD) patients have the highest risk of cardiovascular (CV) outcomes among patients with established atherosclerotic cardiovascular disease (ASCVD). Inclisiran, an siRNA targeting PCSK9 mRNA, reduces LDL-C levels. In SIRIUS in silico trial (NCT05974345), inclisiran was predicted to lower CV events in ASCVD patients.

Research question/Hypothesis:
SIRIUS in silico study aims to predict the efficacy of inclisiran on CV outcomes in subgroups of patients with or without PAD.

Methods:
The SIRIUS in silico trial was conducted using a knowledge-based mechanistic computational model of ASCVD applied to a virtual ASCVD population with LDL-C ≥ 70 mg/dL. Each virtual patient is its own control. This model was previously calibrated and validated before running the trial. SIRIUS compared the efficacy of inclisiran vs placebo on top of High Intensity (HI) statins with or without ezetimibe on 3-Point-MACE defined as a composite of time to first occurrence of CV death, nonfatal myocardial infarction (MI) or nonfatal ischemic stroke (IS) over 5 years. Occurrence of major acute limb events (MALE) was also individually assessed in time-to-first-event analyses.

Results:
Among 204, 691 virtual SIRIUS ASCVD patients, 28,072 (13.7%) had PAD. At 5 years, the mean predicted percentage reduction in LDL-C with inclisiran as compared to placebo was -49.3% and -49.8% in patients with or without PAD, respectively. The predicted rate of 3P-MACE in the inclisiran arm was consistently lower than in the placebo arm in patients with PAD (17.62% vs 22.88%; Hazard Ratio (HR): 0.75 medium uncertainty) and in patients without PAD (10.33% vs 13.64%; HR: 0.75 low uncertainty). Compared to placebo, inclisiran was also predicted to consistently reduce MALE in patients with or without PAD (2.71% vs 4.11%; HR: 0.65 medium uncertainty and 0.19% vs 0.29%; HR: 0.66 high uncertainty respectively).

Conclusion:
Pending the results of ORION-4 and VICTORION-2-P, this first In Silico trial in virtual PAD patients predicted a potential effect of inclisiran on 3P-MACE and MALE reductions over 5 years follow-up.
Abstract 4139170: Relationship between hemodynamics and oxygen consumption in hypertrophic cardiomyopathy during maximal stress testing
Authors: Parrish Jonathan , Blain Alasdair , Okwose Nduka , Fuller Amy , Alyahya Alaa , Russell Sophie , Eggett Christopher , Luke Peter , Bailey Kristian , MacGowan Guy , Jakovljevic Djordje , Charman Sarah
Published: November 2024

Background:
Hypertrophic cardiomyopathy (HCM) is a global heart disease with great variability in disease severity, which can lead to significant impairment of exercise capacity. In healthy populations, oxygen consumption is related to cardiac output and arteriovenous oxygen difference. We sought to determine the relationship between hemodynamics (cardiac output and stroke volume) and oxygen consumption in HCM compared to healthy controls during maximal stress testing.

Aims:
To evaluate associations between the trajectories of hemodynamic function and oxygen consumption in HCM compared to healthy controls.

Methods:
Twenty individuals with HCM (51±15 years old, body mass index (BMI): 28±3 kg/m
2
, females, n=4) and 16 healthy controls (66±7 years old, 27±6 kg/m
2
, females, n=6) were included in the present study. Participants completed a maximal-graded stress test coupled with non-invasive hemodynamic bioreactance (cardiac output, stroke volume) and gas exchange (oxygen consumption, VO
2
) measurements. Data were analyzed in quartiles (exercise only) and phases (rest, pre-pedalling, exercise and recovery) of the maximal-graded stress test.

Results:
In HCM, cardiac output declined in the fourth quartile of the exercise phase of the stress test (-0.39 L/min,
p
<0.001) whilst VO
2
increased (3.86 ml/kg/min,
p
<0.001). There was a significant difference in the gradient of cardiac output between HCM and controls in the final quartile of the test (-1.6 vs. 18.1 L/min, p<0.001). In coherence, stroke volume declined in the fourth quartile of the test (-18.4 ml,
p
<0.01) in response to increasing VO
2
in HCM. The rates of recovery were faster in HCM compared to the control group for VO
2
(-4.3 vs -2.6 mL/second, p<0.001), cardiac output (-0.03 vs -0.02 L/second, p<0.001), heart rate (-0.17 vs -0.10 beats/second, p<0.001), and stroke volume (-0.18 vs -0.07 L/second, p<0.001).

Conclusions:
In HCM, cardiac output declined during the later stages of maximal stress testing whereas in controls it continued to rise, indicating impaired maximal cardiac output responses to exercise. These findings have implications for exercise prescription and training regimens in HCM suggesting avoidance of maximal exercise levels.
Abstract 4139188: Myocardial perfusion, oxidative metabolism and fibrosis in heart failure with preserved ejection fraction
Authors: Mallugari Ravinder , Reynolds Cassandra , Gottlieb JoAnn , Bozeman Shannon , Fuhs Dana , Hughes Sean , Bradham William , Lawson Mark , Kronenberg Marvin , Gupta Deepak
Published: November 2024

Background:
Cardiac remodeling among individuals with heart failure with preserved ejection fraction (HFpEF) and its risk factors is incompletely understood. Non-invasive cardiac imaging can reliably assess myocardial oxidative metabolism, perfusion, fibrosis, systolic and diastolic function. Nevertheless, the interrelationships between these, particularly with oxidative metabolism, remain unresolved from health to HFpEF as most human studies lack complementary multi-modality imaging.

Methods:
We performed a cross-sectional study using multi-modality cardiovascular imaging in healthy individuals (n=17), those with hypertension (n=15), and patients with HFpEF (n=8). We quantified myocardial oxidative metabolism (K
mono
) with
11
C-acetate positron emission tomography (PET), coronary flow reserve (CFR) with
13
N-ammonia PET, fibrosis (extracellular volume [ECV], LVEF and mass with magnetic resonance imaging (MRI), and LV diastolic filling pressure (E/e’) by echocardiography. The associations between myocardial oxidative metabolism, perfusion, and fibrosis across clinical status (health, hypertension, and HFpEF) were examined in multivariable models.

Results:
From health to HFpEF, we found significant graded
declines
in oxidative metabolism indexed to workload (K
mono
/RPP) (β = -1.66 x 10
-6
[95%CI: -3.12 x 10
-6
to -2.10 x 10
-6
]; p = 0.027) and CFR (β = -0.76 [95% CI: -1.36 to -0.16]; p = 0.021), along with increased fibrosis (ECV) (β = 2.12% [95% CI: 0.10 to 4.14%]; p = 0.041), independent of LVEF, LV mass, E/e’, age, sex, and body mass index. The decline in oxidative metabolism from health to HFpEF was also independent of ECV and CFR (β = -2.98 x 10
-6
[95% CI: -5.62 x 10
-6
to -3.41 x 10
-6
], p = 0.015). In contrast, the decline in CFR from health to HFpEF was no longer significant (p = 0.30) with further adjustment for ECV.

Conclusions:
HFpEF and its development involves progressive declines in myocardial oxidative metabolism and perfusion reserve with increase in fibrosis. The decline in myocardial oxidative metabolism from health to HFpEF is independent of fibrosis and perfusion reserve, suggesting oxidative metabolism may be a target for the prevention and treatment of HFpEF.
Abstract 4139198: A Systematic Approach to Prompting Large Language Models for Automated Feature Extraction from Cardiovascular Imaging Reports
Authors: Goldfinger Shir , Mackay Emily , Chan Trevor , Eswar Vikram , Grasfield Rachel , Yan Vivian , Barreto David , Pouch Alison
Published: November 2024

Introduction:
Cardiovascular radiology reports contain valuable diagnostic information linked to images, but the unstructured text format makes feature extraction difficult on a large scale. Large language models (LLMs) allow for feature extraction where string parsing alone is insufficient, but require careful prompting for accurate results.

Hypothesis:
We hypothesize that a systematic prompting approach using LLMs can expedite the extraction of features from unstructured text in transesophageal echocardiography (TEE) reports.

Methods:
The data consisted of 7106 intraoperative TEE reports, 600 of which were manually reviewed to obtain pre- and post-intervention ground truth values for left ventricular ejection fraction (LVEF), right ventricular systolic function (RVSF), and tricuspid regurgitation (TR). Reports are paired with an imaging study consisting of 50-200 clips. For each feature considered, 100 of the 600 labeled reports were used to engineer a prompt in Llama-2 that maximized feature extraction accuracy.

Results:
We found that using multiple, shorter prompts yielded higher accuracy than did fewer, longer prompts. Additionally, when imposing semantic information onto a numerical scale, prompt engineering in combination with string parsing (Figure 1) gave the best results. When evaluated on the 500 labeled reports withheld for testing, the finalized prompts had accuracies of 94.1%, 94.8%, and 91.3% for LVEF, RVSF, and TR, respectively. Using this strategy, 5000 intraoperative TEE reports were analyzed and used to train and evaluate a regression model for LVEF estimation from TEE clips (Figure 2).

Conclusion:
We have shown that performing prompt engineering on Llama-2 can be used to extract features from unstructured TEE reports in an accurate manner. As an extension of these methods, automated feature prediction from echocardiograms can be used to create rapid, low-cost, and accessible cardiac assessments.