bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4137534: Troponin Can Predict Late Gadolinium Enhancement on Cardiac MRI in COVID-19 Vaccine-Associated Myocarditis
Authors: Jain Supriya , Anderson Steven , Steele Jeremy , Wilson Hunter , Muniz Juan Carlos , Soslow Jonathan , Beroukhim Rebecca , Maksymiuk Victoria , Jacquemyn Xander , Dorfman Adam , Fonseca Brian , Buddhe Sujatha , Ashwath Ravi , Thacker Deepika , Maskatia Shiraz , Misra Nilanjana , Su Jennifer , Siddiqui Saira , Vaiyani Danish , Vaikom House Aswathy , Campbell Michael , Klein Jared , Huang Sihong , Mathis Christopher , Cornicelli Matthew , Sharma Madhu , Nagaraju Lakshmi , uppu santosh , Ramachandran Preeti , Patel Jyoti , Han Frank , Bhatla Puneet , DiLorenzo Michael , Eshtehardi Parham , Drugge Elizabeth , Grosse-Wortmann Lars
Published: November 2024

Background/Aim:
We previously reported that late gadolinium enhancement (LGE) on cardiac MRI (CMR) was as high as 82% in pediatric patients with COVID-19 vaccine-associated myocarditis (C-VAM) despite mild clinical symptoms and normal left ventricular function. As LGE can be a harbinger for future adverse events including arrhythmias, heart failure or sudden cardiac death, we sought to identify predictors for LGE in C-VAM, specifically assessing troponin as a screening marker for C-VAM patients at risk for myocardial scarring who could then be referred for a confirmatory CMR with LGE.

Methods:
In this longitudinal multicenter retrospective observational study across 38 U.S. member institutions of the
M
yocarditis
A
fter
C
OVID
V
accination (MACiV) study network, 333 patients with C-VAM based on CDC criteria were included from April 2021 to November 2022. Data collected included demographics, laboratory values, clinical and cardiac imaging characteristics and outcomes. Using logistic regression, troponin levels at presentation were assessed as a log transformed continuous variable and categorized into tertiles.

Results:
The C-VAM patients were predominantly white (67%) adolescent males (91%, 15.7± 2.8 years). There were 216/333 (65%) patients who had both a reported troponin value and had a CMR. On univariate analysis, elevated troponin increased the probability of having LGE (OR=1.29, 95% CI: 1.06, 1.58, p=0.012). Even after controlling for age, race, sex, number of vaccine doses and left ventricular ejection fraction (OR=1.32, 95% CI: 1.06, 1.65, p=0.013). Patients >15 years compared to those ≤15 years of age were 2.94 (95% CI: 1.28, 6.75, p=0.011) times more likely to have LGE at presentation. Patients with troponin levels in the highest tertile compared to lowest tertile were 2.66 times (95% CI: 1.04, 6.83, p=0.042) more likely to have LGE along with a greater involvement > 4 AHA myocardial segments with LGE (p=0.004)

Conclusions:
Higher troponin values are associated with presence of late gadolinium enhancement on cardiac MRI in patients with COVID-19 vaccine-associated myocarditis. Troponin levels at presentation may facilitate risk stratification and function as a screening tool to identify those C-VAM patients with the greatest likelihood of myocardial scarring, who may benefit from undergoing CMR for tissue characterization.
Abstract 4137535: Gastrointestinal Bleeding Risk: Diltiazem versus Metoprolol in Patients on Rivaroxaban, Apixaban, or Dabigatran.
Authors: Seylani Allen , Haile Yohannes , Asiedu Samuel , Shahin Hania
Published: November 2024

Introduction:
A recent JAMA study by Ray et al., reported severe bleeding risk among older adults with atrial fibrillation (Afib) receiving apixaban or rivaroxaban along with diltiazem compared to metoprolol. Our investigation extended to evaluating the gastrointestinal (GI) bleeding risk associated with various Xa inhibitors and dabigatran when combined with either diltiazem, or metoprolol among all adults ages 18 and older.

Method:
We conducted a comparative retrospective cohort study using de-identified patient data obtained from the global network of the TriNetX platform, a comprehensive electronic health records system comprising 120 healthcare systems and more than 147 million patients worldwide. The cohorts were divided into patients treated with diltiazem vs. metoprolol while receiving apixaban or rivaroxaban (Cohort A), patients receiving metoprolol with apixaban vs. rivaroxaban treatment (Cohort B), patients treated with diltiazem with apixaban vs rivaroxaban (Cohort C), and patients treated with diltiazem vs metoprolol who received dabigatran (Cohort D). The risk of gastrointestinal hemorrhage among the cohorts was evaluated. Propensity score matching was employed to balance baseline characteristics between the cohorts, including age, sex, ethnicity, and comorbidities.

Results:
The risk of GI bleed in patients taking diltiazem with either apixaban or rivaroxaban was 6.3%, while the risk in patients taking metoprolol with either of these Xa inhibitors was 5.7 % (p< 0.0001, 95%CI (1.074,1.111), RR 1.09. In patients taking metoprolol with apixaban, GI bleed risk was 5.4%, compared to 6.4% in those taking metoprolol with rivaroxaban (p< 0.0001, 95% CI (0.838, 0.868), RR 0.85. For patients taking diltiazem with rivaroxaban, GI bleed risk was 7.3%, whereas it was 5.8% in those taking diltiazem with apixaban (p< 0.0001, 95% CI (1.194, 1.265), RR 1.23. Risk of GI bleed in patients taking diltiazem with dabigatran was 7.4%% while it was 6.71% for patients treated with metoprolol and dabigatran (p< 0.0011, CI 95% (1.038,1.16), RR 1.097)

Discussion:
Global patients’ data in this study suggested similar findings reported by Ray et al. Additionally, among all ages adults with Afib, treatment with metoprolol and apixaban was associated with the lower risk of GI bleed when compared with metoprolol and rivaroxaban. While the highest risk of GI bleed was associated with concurrent diltiazem and dabigatran use.
Abstract 4137570: Atherosclerotic Cardiovascular Disease Risks in Children: An electronic health record data analytics approach
Authors: Liu Juanjuan , Garcia Victoria , Van Gieson Maya , Swackhamer Haydn , Lee Tyler , Lee Nicole , Cook Adam , He Alice , Wei Zhenglun , Bailey-Davis Lisa , Ge Shuping
Published: November 2024

Background and Aims:
There is little data on atherosclerotic cardiovascular disease (ASCVD) risk conditions, factors, and tiers in the pediatric population. This study aimed to develop and validate electronic health record (EHR) data analytic algorithms to attain the prevalence of 24 risk conditions, 7 factors, and 4 tiers in children in a rural community.

Methods:
This study included all the 495,902 subjects from 0 to 18 years at the Geisinger Medical Center from 2004 to 2022. The demographic and clinical data were collected using ICD-10 codes, clinical and laboratory data, and a dual-coded computational algorithm was developed based on the AHA guideline to derive the ASCVD risk conditions, factors, and tiers. To validate the EHR algorithms, the algorithm (rater 1) and a clinician (rater 2) extracted and analyzed the data from 40 randomly selected subjects from this cohort. Kendall’s coefficient of concordance (W) and Gwet’s agreement coefficient were used to evaluate algorithm and clinician agreement within the ASCVD tiers, conditions and factors, respectively.

Results:
High concordance was observed between algorithmic and clinician raters for risk tiers (W=80%), conditions (80-97%), and factors (49% for blood pressure, and 92% to 97% for the rest of the risk factors). In this cohort, the median age was 3.9 years, 51.0% were male, 80.6% were Non-Hispanic/Latino, and 88.1% were White. Overall, 15.5% (N = 76,945) were at-risk, 7.0% (N = 34,530) at moderate risk, and 4.2% (N = 20,761) at high risk for ASCVD, respectively. The most prevalent risk conditions were obesity (9.1%, N = 45,074), chronic inflammatory conditions (6.8%, N = 33,685), severe obesity (2.7%, N = 13,442), insulin resistance with comorbidities (2.7%, N = 13,397), and hypertension (2.1%, N = 10,436). The most prevalent risk factors were elevated BMI (27.4%, N = 135,904), blood pressure (12.5%, N = 62,015), and fasting lipid profile (8.7%, N = 43,100).

Conclusion:
Our EHR data analytics algorithm is in high agreement with the clinician rater. The high, moderate, and at-risk ASCVD risk tiers are prevalent in a large contemporary pediatric cohort at Geisinger. Both ASCVD risk conditions and factors are also prevalent, especially obesity, diabetes, hypertension, and hyperlipidemia. These findings suggest the further application and refinement of these algorithms to design innovative approaches for ASCVD risk reduction and prevention in children.
Abstract 4137644: Association of Prolonged QTc with Development of Heart Failure after Hematopoietic Stem Cell Transplantation
Authors: Shu Lihua , Vasbinder Alexi , Catalan Tonimarie , Machado Kristen , Ismail Anis , Hutten Christina , Pizzo Ian , Huang Yiyuan , Blakely Pennelope , Banerjee Mousumi , Leja Monika , Hayek Salim
Published: November 2024

Background:
Use of hematopoietic stem cell transplantation (HSCT) continues to rise in the United States, particularly in older age groups; however, HSCT is associated with various cardiovascular complications including heart failure (HF). We sought to examine whether prolonged QTc prior to HSCT was associated with the risk of HF post-HSCT.

Methods:
We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center (RUMC) between 2008-2019. In this analysis, only patients from the UMHS site were included (n=2,435). Baseline electrocardiogram (EKG) data were recorded prior to transplant (median (IQR) 14 (3, 30) days). QTc prolongation was defined per CTCAE grading criteria as Normal (<440ms), Grade 1 (440-480ms), and Grade ≥2 (>480ms). The primary outcome was new-onset HF defined as a diagnosis documented by health care providers after the date of hospitalization for HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT cardiovascular risk score.

Results:
Of the 2,435 patients (mean age at HSCT 55±13.4 years; 59.7% male; 90.5% White), 534 (21.9%) had long QTc pre-HSCT. Of those, 440 were Grade 1 and 94 were Grade ≥2. In all, 138 HF events occurred over median period of 2.3 (1.0-5.3) years. The 5-year cumulative incidence of HF was 5.0% in patients with normal QTc, 8.4% in patients with Grade 1 QTc prolongation, and 19.0% in patients with Grade ≥2 QTc prolongation (Figure). Patients with Grade 1 and Grade ≥2 prolongation had a 1.57 (95% CI: 1.05, 2.33) and 2.71 (95% CI: 1.51, 4.86) times higher risk of HF, respectively, compared to those with normal QTc.

Conclusions:
In this contemporary cohort of adult HSCT patients, those with QTc prolongation prior to HSCT had a higher incidence of HF compared to normal QTc, with greater degree of prolongation associated with higher risk. These findings highlight the importance of accounting for the QTc as part of the pre-transplant cardiovascular evaluation
Abstract 4137678: Maximal Oxygen Uptake Prediction From Resting and Submaximal Variables of Cardiopulmonary Exercise Testing by Using Machine Learning Methods
Authors: Lee YongHun , Feng Jeffrey , Rahrooh Al , Bui Alex , Cooper Christopher , Hsu Jeffrey
Published: November 2024

Background:
Cardiorespiratory fitness, as measured by maximal oxygen consumption (VO2max) during a cardiopulmonary exercise test (CPET), is a prognostic indicator for longevity and adverse cardiovascular event prevention. This study aims to formulate a regression model utilizing resting and submaximal variables during CPET evaluation in the general population to predict VO2max.

Methods:
We used 13,535 CPET results on cycle ergometer collected by the UCLA Exercise Physiology Research Laboratory over eight years. Patients were divided into a normal group (NG; n=1,400) and an other group (OG; n=12,135). The inclusion criteria for the NG were: the absence of any known clinical diagnosis, BMI <30, no current use of beta blocker, and VO2max >85% of the predicted value for age and sex (Wasserman equation). OG refers to all other patients not in NG. Models were trained and evaluated for each group using stratified 5-fold cross-validation. We also trained different models using only resting variables (R-VARS) and resting and submaximal exercise variables (R+S-VARS). Feature importance was assessed using Shapely additive explanations (SHAP) values to identify how the feature related to the VO2max prediction.

Results:
The regression models were trained on the NG, OG, and total (N+OG) groups. The optimal models were Bayesian Ridge for the NG and Light Gradient Boosting Machine for the other two groups. The mean (standard deviation) R2 when using only R-VARS was 0.67(0.037) for the NG, 0.54 (0.014) for the OG, and 0.55 (0.009) for the N+OG. When using R+S-VARS, performance increased to 0.82 (0.014) for the NG, 0.80 (0.010) for the OG, and 0.8 (0.008) for the N+OG. Chronotropic index (ci), body mass index (BMI), VO2 at the first ventilatory threshold (VO2h1kg), minute ventilation at the second ventilatory threshold (VEH2), and forced expiratory volume (FEV1) were important features across the models trained with R+S-VARS. CI, BMI, and VEH2 had a negative effect, while VO2h1kg, FEV1 had positive effect on VO2max prediction.

Conclusion:
Our VO2max prediction model demonstrated remarkable accuracy in this dataset representing a generally healthy, non-athlete population using R+S-VARS. Particularly noteworthy was the enhanced performance within subgroups exhibiting a lower VO2max. This methodology offers a means to assess VO2max for individuals who might not achieve maximal exhaustion during CPET due to non-cardiopulmonary reasons.
Abstract 4137688: Inhibition of Cardiac Fibrosis and Pro-Fibrotic Collagen Hormone Endotrophin by VS-041, a Novel Drug Candidate for Heart Failure with Preserved Ejection Fraction
Authors: Plonowski Artur , Berger Joel , Pratt Benjamin , Krupa Magdalena , Vekich John , Bochenek Wieslaw , Larson Christopher , Moreno Ydalina , Genovese Federica
Published: November 2024

Introduction:
Endotrophin, a collagen type VI–derived signaling peptide, has been linked to cardiac metabolic dysregulation, inflammation, and fibrosis. Several matrix metalloproteinases (MMPs), incl. MMP2 and MMP9, have been shown to cleave collagen 6A3 and release endotrophin. Baseline plasma endotrophin levels in heart failure with preserved ejection fraction (HFpEF) patients were shown to be strongly and independently associated with increased risk of poor outcomes (death or HF-admissions).

VS-041 is a novel drug candidate for HFpEF that inhibits key MMPs implicated in cardiac fibrosis and diastolic dysfunction. Previously, VS-041 demonstrated robust efficacy in the Dahl Salt Sensitive rat model of hypertension and HFpEF, improving diastolic function and dose-proportionally reducing left ventricle (LV) fibrosis.

Hypothesis:
Inhibition of endotrophin release by VS-041 could contribute to its anti-fibrotic mechanism and serve as a potential biomarker of MMP inhibition (target engagement) in patients.

Methods and Results:
The effect of VS-041 on production of endotrophin was investigated in a “Scar-in-a-Jar” model using primary human cardiac fibroblasts isolated from adult healthy ventricles. Fibroblasts were treated with 10 ng/mL platelet-derived growth factor (PDGF) AB in the presence of 0.03, 0.3, or 3 µM VS-041, or DMSO control. The concentration of endotrophin in the medium was assessed via the ELISA nordicPRO-C6
TM
(Nordic Bioscience A/S). After 4 days of treatment, VS-041 at 0.3 µM and 3 µM significantly inhibited PDGF AB-stimulated production of endotrophin. Cumulative inhibitory effects of VS-041 could still be observed after 12 days of culture. The antifibrotic activity of VS-041 was also tested in a model of extensive cardiac fibrosis in 16-months old C57BL/6 mice exacerbated by angiotensin II infusion at 1 mg/kg/day for 28 days. Oral treatment with VS-041 at 75 mg/kg BID resulted in a 62% reduction (p<0.01) of LV fibrosis as assessed by morphometry of Masson trichrome stained sections. VS-041 also improved the diastolic echocardiography parameters IVRT and E/a ratio.

Conclusions:
The production of endotrophin by fibroblasts is diminished by VS-041 and, therefore, its plasma levels could be explored as a biomarker of in vivo MMP inhibition by VS-041. Additionally, the inhibition of endotrophin release by VS-041 could be causatively linked to reduction of cardiac fibrosis and potentially translate into improved clinical outcomes in HFpEF patients.
Abstract 4137716: Development and Content Validation of the Heart Failure Symptom Management Motivation Questionnaire
Authors: da Costa Ferreira Oberfrank Natany , Liu Wen , Dunn-Lopez Karen
Published: November 2024

Introduction:
Adequate heart failure (HF) self-management is crucial for alleviating distressing symptoms. While disease knowledge is important, it is insufficient for sustained self-care. Patient motivation plays a key role in successful self-management interventions. However, tools assessing motivation for HF symptom self-management are lacking.

Aims:
To develop the Heart Failure Symptom Management Motivation (HF-SMM) questionnaire and assess its content validity with nurse experts.

Methods:
A cross-sectional study occurred in three phases from November 2022 to April 2024. Initially, we conducted a systematic review to identify motivation assessment instruments for cardiovascular self-care and assess their psychometric properties. We then designed the HF-SMM items based on existing tools, guidelines, and clinical expertise, focusing on four HF symptoms: anxiety, depression, edema, and fatigue. The questionnaire comprised three subscales: autonomous motivation, controlled motivation, and amotivation. Nurse experts with doctoral degrees and HF experience assessed 96 items about questionnaire clarity and relevance via Delphi rounds, using a 4-point Likert scale. Items with a content validity index (I-CVI) between .80 to 1.00 were deemed acceptable. The average I-CVI of all items resulted in the scale content validity index average (S-CVI/Ave) with a cutoff point of .90.

Results:
We invited ten experts, with nine participating. They had an average of 17.1 ± 10.7 years of HF clinical experience and 11.6 ± 7.4 years of research experience. In the initial Delphi round, items scored I-CVI ranging from .44 to 1.00 for anxiety, depression, and fatigue, and .66 to 1.00 for edema, resulting in an S-CVI/Ave of .81. After the first round, 54 items with I-CVI >.80 were retained (56.2%), and 42 items were revised (43.8%). A second Delphi round, with 77.7% of the original experts, showed most items with excellent I-CVI scores (> .80; 84; 87.5%), with only ten items needing clarity revisions (10.4%). The overall CVI of the questionnaire was excellent with a S-CVI/ Ave of .90 after two rounds of validation.

Conclusions:
The HF-SMM questionnaire demonstrates excellent content validity for assessing motivation in HF self-management. Future studies should incorporate cognitive interviews to understand better patient perceptions about the items.
Abstract 4137796: Novel Deep Learning Aligned Strain Techniques in Repaired Tetralogy of Fallot
Authors: Koehler Sven , Deng Lifu , Shah Ansh , Mascha Edward , Li Shuyi , Nguyen Christopher , Karamlou Tara , Geva Tal , Valente Anne , Lee Ji Hae , Latus Heiner , Pickardt Thomas , Greil F. Gerald , Beerbaum Philipp , Sarikouch Samir , Hussain Mohammad , Engelhardt Sandy , Tandon Animesh
Published: November 2024

Introduction:
Multicenter studies show that demographic and CMR-based volumetrics and strain predict death, ventricular tachycardia and fibrillation (DVTF) in repaired tetralogy of Fallot (rTOF). We developed a novel deep learning method to calculate radial (RS) and circumferential strain (CS) from end-diastole (ED) to other key frames: mid systole (MS), end-systole (ES), peak flow (PF) in diastole, and mid-diastole (MD) (called ED2K), as well as from each key frame to the next (called K2K strain), for each left ventricle (LV) segment.

Hypothesis:
We hypothesized that: H1) ED-ES strain; H2) septal strain; and H3) diastolic strain would be additionally predictive of DVTF as compared to a traditional model.

Approach:
704 patients combined from the German Competence Network and INDICATOR cohorts had ED2K and K2K strain values calculated using CMR short axis stack.

We first created a 4-variable “traditional” logistic regression model including age at CMR, RVEF%, LVEF% and RVESVi. We then separately added ED2K and K2K parameters to assess increased ability to discriminate DVTF, measured by the c-statistic.

Results:
In univariate analyses, H1: ED to ES RS and CS; H2: multiple systolic septal and non-septal variables; and H3: overall diastolic RS and CS were significantly associated with DVTF, with c-statistics between 0.65 and 0.73 (n=56, Table 1). When added to the traditional model, H1: ED to ES CS; and H2: septal and non-septal CS slightly improved model performance (Table 2). Model calibration was adequate for all models.

Conclusion:
Our key-frame specific strain recapitulates the CS prediction of adverse events in rTOF, and slightly improves prediction in a multiparameter model. Future work includes external validation.
Abstract 4137820: Extreme heat and cardiovascular disease in a changing climate: An urgent need for risk management and health research
Authors: Wang Xiaowen , Wang Liyun , Ji John S. , Huang Cunrui
Published: November 2024

Background:
Extreme heat can trigger or exacerbate cardiovascular disease (CVD) through ischemia or thrombosis, and its deleterious impacts are inclined to worsen as increased heat exposure and heightened vulnerability from climate change interacted with natural and social environment.

Research Questions:
Previous studies have primarily focused on quantifying the increased risk of CVD due to heat exposure, while lacking a comprehensive understanding of the association, underlying mechanisms, and vulnerability in CVD patients. Consequently, there is a scarcity of clinical and public health interventions aimed at preventing the convergence of extreme heat exposure and the risk of CVD within the context of climate change.

Methods:
We conducted a systematic search in PubMed, Embase, and Web of Science from inception to December, 2023, and we retrieved articles which assessed the effects of extreme heat or climate change on CVD.

Results:
In this review, we outline the existing evidence on the epidemiology and pathophysiological mechanisms that elucidate how extreme heat affects the risk of CVD. Extreme heat is associated with increased risks for CVD morbidity and mortality, where older persons, low socioeconomic status, pre-existing medical conditions, and unfavorable living environments confer greater susceptibility to heat. The adverse effects of extreme heat on cardiovascular system involved a wide range of complex mechanisms between different organs and regulatory pathways (Figure 1). Additionally, we identify the factors that contribute to the vulnerability of CVD patients to heat exposure. The discrepancy in heat-related risk can be attributed to individual susceptibility, sociocultural factors, population temperature adaptations, and environmental factors. Future climate change is projected to exacerbate the burden of extreme heat, particularly due to the interaction of air pollution, population aging, and urbanization (Figure 2).

Conclusions:
Addressing extreme heat should be within the framework of the prevention of CVD. Health professionals and scientists are responsible for mitigating the cardiovascular effects mediated by extreme heat, with an emphasis on engaging in risk management tactics and health research to implement preventive strategies. As CVD is a climate sensitive disease, evidence-based interventions during heat extremes are urgently needed to cope with the cardiovascular risks associated with the inevitable trajectory of climate change.
Abstract 4137823: Influence of Hospital and Cardiac Rehabilitation Facility Proximity on Enrollment Rates Among Medicare Beneficiaries
Authors: Khan Usman , Yang Jie , Hawkins Robert , Keteyian Steven , Likosky Donald , Thompson Mike , Fu Whitney , Sukul Devraj
Published: November 2024

Background:
Participation in cardiac rehabilitation (CR) is enhanced by proximity to CR facilities and communication between inpatient and outpatient settings but may become fragmented when patients are distant from their discharging hospital and nearest CR facility.

Research Question:
This study investigates how patient distance to both hospitals and CR facilities impacts the rates of CR participation.

Methods:
This study included 100% Medicare fee-for-service claims for beneficiaries with 12 months of continuous Part A/B coverage who had coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or surgical or transcatheter aortic valve replacements (SAVR or TAVR) between 07/2016-12/2018, excluding patients discharged to hospice or died within 30 days. Google Maps defined travel distances from the patient to hospital and CR facility locations using geographic centroids of ZIP codes, which were then categorized into quartiles. CR enrollment was defined as attending at least one session within one year of discharge. Logistic regression models estimated marginal CR enrollment rates across both hospital and CR facility distance categories adjusting for patient, hospital, and regional factors.

Results:
The study included a total sample of 501,049 beneficiaries undergoing PCI (62%), CABG (19%), SAVR (7%), and/or TAVR (15%). The median travel distance to the hospital was 18.6 miles (IQR 8.2-43.3 miles) and to the CR facility was 7.7 miles (IQR 2-15.3 miles). A total of 188,963 (37.7%) beneficiaries attended at least one CR session, which varied across categories of distance to hospital (Q1: 36.8% to Q4: 37.5%) and CR facility (Q1: 44.7% to Q4: 30.0%, p<0.01). Adjusted CR enrollment rates improved when beneficiaries lived farther from their admitting hospitals but closer to CR facilities (Figure 1), with the highest enrollment for those located farthest from their admitting hospital but closest to the CR facility (47.5%) and lowest enrollment among those closest to the hospital but farthest from the CR facility (20.6%).

Conclusions:
Greater distance to the admitting hospital was associated with higher CR enrollment, while greater distance to the CR facility was associated with lower enrollment among eligible Medicare beneficiaries. Addressing geographic barriers to CR participation may require tailored solutions based on patient proximity to hospitals and CR facilities.
Abstract 4137880: Access to exercise opportunities, physical inactivity and cardiovascular mortality: A nationwide study in the U.S.
Authors: Wang Xiaowen , Gu Yongshi , Wang Ying , Qu Yuqing , Chen Tianling , Hopke Philip K. , Zhang Kai , Hao Yuantao , Zhang Wangjian
Published: November 2024

Aims:
Despite efforts to promote physical activity, the prevalence of physical inactivity continues to rise. Exercise access influences population activity levels, but county-level variation in physical activity and its link to cardiovascular disease (CVD) mortality is unclear. We explored the associations between access to exercise opportunities, levels of physical inactivity, and CVD mortality across U.S. counties

Methods:
The County Health Rankings and Roadmaps data and CDC WONDER mortality data were integrated. We compared age-adjusted CVD mortality across county-level quartiles of access to exercise opportunities and physical inactivity. Stratification was performed based on age, sex, race, and urbanization. The rate ratio (RR) for CVD mortality was calculated using generalized linear models.

Results:
CVD mortality decreased from high to low values of the county-level of physical activity across all demographic subgroups (P<0.001) (Table 1&Figure 1). Access to exercise opportunities was significantly associated with a reduced risk of CVD mortality (RR, 0.93 [0.91–0.95]), which was most pronounced in relation to acute myocardial infarction (AMI) mortality (RR, 0.80 [0.76–0.85]). The county-level physical inactivity was associated with an increased risk of CVD mortality (RR, 1.16 [1.14–1.17]), especially for ischemic heart disease (IHD) mortality (RR, 1.35 [1.31–1.38]) and AMI mortality (RR, 1.32 [1.25–1.38]) (Figure 2). All demographic subgroups demonstrated similar benefits by improving the county-level indicators of physical activity.

Conclusion:
Counties have the potential to make significant strides in preventing CVD and improving the cardiovascular health of their populations by enhancing access to exercise opportunities and reducing physical inactivity.
Abstract 4137905: The association between prehospital epinephrine administration and short-term outcomes in patients with shockable out-of-hospital cardiac arrest and extracorporeal cardiopulmonary resuscitation: a propensity matched analysis
Authors: Kawakami Shoji , Hidenobu Koga , Yamada Tetsuhisa , Nishi Junichiro
Published: November 2024

Background:
In out-of-hospital cardiac arrest (OHCA) patients with an initial shockable rhythm, epinephrine increases the likelihood of return of spontaneous circulation (ROSC), but its effect on neurological outcome remains uncertain. Epinephrine administered before extracorporeal resuscitation (ECPR), which is a non-pharmacological method to obtain ROSC, may have worsened neurological outcome.

Aim:
To evaluate the impact of prehospital epinephrine administration on the prognosis of OHCA patients undergoing ECPR.

Methods:
This is a retrospective analysis of a cohort study from a multicenter, prospective registry of 81234 OHCA patients between 2014 and 2021. After the application of exclusion criteria, 1061 OHCA patients with an initial shockable rhythm and who underwent ECPR were eligible for this study. The primary outcome was favorable neurological outcome at 30 days after the OHCA and the secondary outcome was ROSC during transfer. Patients who did and did not receive prehospital epinephrine were propensity score-matched on the basis of age, gender, witness arrest, bystander-initiated CPR, dispatcher-assisted CPR, advanced airway management, call-to-defibrillation interval, year and district.

Results:
Among 1061 eligible patients, 442 patients received epinephrine and 619 patients did not. Matching was successful in achieving covariate balance as shown by a standardized difference of <10% for all variables (329 matched pairs). The proportion of patients with prehospital ROSC was significantly higher in those who received prehospital epinephrine than those who did not (36 [8%] vs 31 [5%]; adjusted odds ratio [OR] after propensity score-matching, 1.96 [95% CI 1.05-3.67], p=0.03). The proportion of patients with favorable neurological outcome at 30 days was not significantly lower in those who received prehospital epinephrine than those who did not (34 [8%] vs 78 [13%]; adjusted OR after propensity score-matching, 0.78 [95% CI 0.45-1.37], p=0.39).

Conclusion:
In patients with shockable OHCA and ECPR, prehospital epinephrine administration was significantly associated with increased ROSC before hospital arrival and not significantly with decreased favorable neurological outcome at 30 days.
Abstract 4137907: Elevated Plasma Neopterin Levels in Patients with Takotsubo Cardiomyopathy
Authors: Kashima Yumi , Nakagawa Masashi , Kure Yusuke , Matsuo Masanori , Sakamoto Yuya , Shimeno Kenji , Matsumoto Ryo , Matsumura Yoshiki , Abe Yukio , Naruko Takahiko
Published: November 2024

Background:
Takotsubo cardiomyopathy (TC) is characterized by left ventricular apical ballooning and intact coronary arteries. The pathogenesis of this disorder is likely to be catecholamine-mediated myocyte damage, microvascular dysfunction and subsequent oxidative stress; however, a number of possible alternative theories have been suggested. Neopterin is produced by activated macrophages following stimulation by interferon-g produced by T-lymphocytes and is capable of enhancing the oxidative potential of reactive oxygen species. The aim of this study was to compare plasma neopterin levels between TC patients and patients with coronary artery disease.

Methods:
Plasma neopterin levels were measured on admission in patients with TC (n=37), stable angina pectoris (SAP, n=66), unstable angina pectoris (UAP, n=72) and acute myocardial infarction (AMI, n=67) using HPLC. A frozen myocardium specimen was obtained by biopsy from a patient with TC and stained for neopterin, macrophages, and microvessels using immunohistochemistry.

Results:
Plasma neopterin levels were significantly higher in TC patients compared with SAP patients (
P
<0.0001) or UAP patients (
P
<0.05), although they were not significantly different from those in AMI patients. In TC patients, plasma neopterin levels correlated positively with neutrophil count (R=0.47, P<0.05) and serum C-reactive protein levels (R=0.38, P<0.05). Immunohistochemical staining showed abundant neopterin-positive macrophages in the myocardium specimen from the patient with TC.

Conclusions:
This study demonstrates, for the first time, that plasma neopterin levels are elevated in TC patients compared with those in SAP and UAP patients. These findings suggest that neopterin may play an important role in the pathophysiology of Takotsubo cardiomyopathy.
Abstract 4137914: Eligibility for Semaglutide in US Adults with Diabetes and Potentially Preventable Cardiovascular Events Projected from the SUSTAIN-6 Trial
Authors: Wong Nathan , Karthikeyan Hridhay , FAN WENJUN
Published: November 2024

Background:
The Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6) trial showed cardiovascular disease (CVD) benefits of semaglutide therapy in patients with type 2 diabetes mellitus (T2DM).

Purpose:
To estimate the number of US adults with T2DM that may be eligible for semaglutide based on SUSTAIN-6 eligibility criteria and the number of preventable CVD events from semaglutide treatment based on observed CVD event reductions in SUSTAIN-6.

Methods:
We included US adults with T2DM from the National Health and Nutrition Examination Survey (NHANES) 2011– 2020 who had eligibility criteria from SUSTAIN-6. This included an HbA1c>7.0%, age
>
50 with established CVD, heart failure, or chronic kidney disease or an age
>
60 with at least one CVD risk factor. We estimated the number of primary composite and secondary CVD endpoints that would occur based on SUSTAIN-6 treated and placebo published event rates, with the difference indicating the number of preventable events (and annualized based on median 2.1 year follow-up time).

Results:
Among 5002 (projected to 34.0 million [M]) adults we identified with T2DM, we estimated 1,132 (6.9 million) (20.3%) to fit SUSTAIN-6 eligibility criteria. Compared to SUSTAIN-6 trial participants, our sample was slightly older, had a higher proportion of Black participants, shorter duration of diabetes, lower HbA1c and diastolic blood pressure, but similar body mass index and systolic blood pressure. Prior history of ischemic heart disease, myocardial infarction, and stroke were also less common in our NHANES sample. From SUSTAIN-6 semaglutide and placebo primary composite CVD event rates of 6.6% and 8.9%, respectively, we estimated 456,060 and 614,990 events would occur, respectively, for a total of 159,930 preventable CVD events, or 75,681 on an annualized basis. We similarly estimated annualized preventable events for secondary outcomes as shown in the Figure.

Conclusion:
Semaglutide may prevent many fatal and non-fatal CVD events if provided to US adults meeting SUSTAIN-6 eligibility criteria. More efforts are needed to educate the healthcare providers on the CVD benefits from newer diabetes therapies, including semaglutide.
Abstract 4137925: Long-term Outcome of Initial Thoracic Endovascular Repair or Medical Therapy in Acute Uncomplicated Type B Aortic Dissection: Real-world Data from a Nationwide Claims-Database in Japan.
Authors: Kimura Yuki , Ohtsu Hiroshi , Yonemoto Naohiro , Azuma Nobuyoshi , Sase Kazuhiro
Published: November 2024

Introduction:
Thoracic endovascular aortic repair (TEVAR) has emerged as a promising treatment option for patients with type B aortic dissection (TBAD). However, there is a lack of evidence regarding the long-term morbidity of initial TEVAR compared to optimal medical therapy (OMT) in acute uncomplicated TBAD (uTBAD).

Objective:
To evaluate real-world data(RWD) on the long-term outcome of Japanese patients with acute uTBAD using a nationwide claims database.

Methods:
This retrospective cohort study utilizes JMDC, a nationwide claims database under Japan's universal healthcare system. We included patients who were initially hospitalized with a diagnosis of acute TBAD. We defined acute uTBAD by excluding those who died within one month, suffered aortic rupture, traumatic thoracic aortic injury, underwent open-chest surgery, experienced stroke or paralysis, or had less than six months of history in the JMDC. Patients who underwent TEVAR within three months of the index hospitalization (TEVAR group) were compared with those who received optimal medical therapy (OMT group). Propensity score (PS) matching was performed based on age, sex, and year of hospitalization. Using the Kaplan-Meier method, we calculated the cumulative rate of all-cause mortality and aorta-related events.

Results:
Of 18,445 patients diagnosed with aortic disease between January 2005 and December 2020, 641 were included in the study (OMT group: n=580, TEVAR group: n=61). After PS-matching, demographics of the groups (OMT_PSM: n=183 vs. TEVAR_PSM: n=61) were female (12.6% vs. 13.1%), median age (54 years [IQR, 48-60] vs. 54 years [IQR, 50-61]) and follow-up time (18 months [8-32] vs. 19 months [9-32]), respectively. Kaplan-Meier curves for the aortic-related events (Figure1, 2) are shown as long-term outcomes.

Conclusions:
This study successfully demonstrated that the estimated 5-year aortic-related event rate in acute uTBAD patients undergoing OMT is approximately 20%, demonstrating the relevance of the RWD source. However, the number of death events in the TEVAR and OMT groups was not sufficient to provide statistical power. Therefore, further studies are warranted to evaluate the long-term prognosis of initial TEVAR for uTBAD.
Abstract 4137927: Physicians’ Misrecognition of Stroke Risk in Patients with Atrial Fibrillation
Authors: Miyama Hiroshi , Ikemura Nobuhiro , Kimura Takehiro , Katsumata Yoshinori , Ueda Ikuko , Tanimoto Kojiro , Takatsuki Seiji , Kohsaka Shun , Ieda Masaki
Published: November 2024

Background:
Current clinical practice guidelines for atrial fibrillation (AF) recommend stroke risk stratification and the use of oral anticoagulants (OACs) for patients at risk. However, physicians’ recognition of patients’ stroke risk may differ from the calculated risk, and the effect of this discrepancy on subsequent care remains unknown.

Aims:
We aimed to document treating physicians’ estimations of individual patients' stroke risk and assess its association with OAC utilization.

Methods:
A multicenter, prospective cohort study was conducted in two outpatient practices in Tokyo, Japan, between 2018 to 2020. Participants included patients with newly diagnosed AF or those referred for initial treatment for AF. Treating physicians were asked to document the patient's estimated risk of stroke in numbers. The estimations were categorized as low risk (<1.0%/year), intermediate risk (1.0%≤ to <2.0%/ year), and high risk (2.0%≤/year). We then calculated patients’ baseline CHA
2
DS
2
-VASc scores and divided them into three risk groups: 0 or 1 point as low risk, 2 points as intermediate risk, and 3 or more points as high risk. Higher risk categorization by physicians was defined as "overestimation," while lower risk categorization was defined as "underestimation." The independent association of physician-patient risk concordance with OAC use was explored by multivariable Logistic regression models.

Results:
Among the 285 patients enrolled in this study (mean age 68±12 years, male 72.6%), the mean CHA
2
DS
2
-VASc score was 2.3±1.6. Physicians correctly estimated stroke risk in 147 patients (51.6%), underestimated it in 25 patients (8.8%) and overestimated it in 113 patients (39.6%). OACs were used in 89.8% of patients whose stroke risk was correctly estimated, 72.0% of those whose stroke risk was underestimated, and 84.1% of patients whose health status was overestimated. After multivariable adjustment, the underestimation of stroke risk was independently associated with less use of OACs (adjusted odds ratio 0.23, 95% CI 0.061-0.85, P=0.028).

Conclusions:
In this cohort study, physician underestimation of stroke risk was not rare and associated with less use of OACs.
Abstract 4137949: Trends in Hypertensive Related Heart Disease Mortality Among Older Adults in the United States, 1999 - 2020
Authors: Arshad Muhammad Sameer , Tharwani Zoaib Habib , Saad Muhammad , Sohail Muhammad Umer , Deepak FNU , Sohail Muhammad Ovais , Kumar Pankaj , Shahid Izza , Memon Muhammad
Published: November 2024

Background:
Hypertensive heart disease (HHD) is a major global health concern that impairs quality of life and causes significant morbidity and mortality, especially among older adults. We aimed to examine the temporal trends in HHD-related mortality in the United States (U.S.) between 1999 to 2020.

Methods:
The CDC WONDER multiple-cause of death database was utilized to identify HHD-related mortality among adults aged ≥ 55 years from 1999 to 2020. Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent change (APC) were calculated and stratified by year, gender, race, and geographic region.

Results:
A total of 1,186,183 HHD-related deaths were recorded among individuals ≥ 55 years old. Overall, AAMR increased from 36.7 in 1999 to 133.9 in 2020. AAMRs showed a steady increase between 1999 and 2017 (APC: 3.72 [95% CI: 2.72 to 4.49]), followed by a surge from 2017 to 2020 (APC: 14.28 [95% CI: 8.21 to 22.93]). Gender-based analysis showed a constantly higher AAMR among older men compared to older women. Variations in AAMR based on race revealed that Non-Hispanic (NH) Black or African American population had the highest AAMRs. Geographic disparities among states showed that the District of Columbia had the highest AAMR while Nebraska had the lowest. The southern U.S. also had a consistently higher AAMR followed by the West, Northeast, and Midwest. Moreover, metropolitan areas had a higher AAMR than nonmetropolitan areas.

Conclusion:
Our findings reveal an increase in HHD-related deaths and demonstrate that NH Blacks consistently bear a higher burden of disease mortality. These insights underscore the importance of integrating demographic and geographic variables into public health planning and interventions.
Abstract 4137964: Electrical Gaps and Outcomes After Redo AF Ablation: Comparative Analysis from the EARNEST-PVI Trial
Authors: Okada Masato , Tanaka Nobuaki , Tanaka Koji , Hirao Yuko , masuda masaharu , Watanabe Tetsuya , Inoue Koichi , Hikoso Shungo , Sunaga Akihiro , Nakatani Daisaku , Sotomi Yohei , Sakata Yasushi
Published: November 2024

Introduction:
The efficacy of extensive ablation strategies in addition to pulmonary vein (PV) isolation is still controversial in persistent atrial fibrillation (AF) ablation. Gaps in previously ablated lesions can induce arrhythmias, potentially decreasing the effectiveness of extensive ablation.

Purpose:
To evaluate the incidence of gaps, gap-related reentry, and subsequent recurrence following redo AF ablation in the EARNEST-PVI trial (NCT03514693).

Methods:
The analysis was performed using the extended data of the EARNEST-PVI trial (N=512), a randomized controlled trial evaluating ablation strategies for persistent AF. Patients were randomized 1:1 to either the PVI-plus or PVI-alone group. During a median follow-up of 47 months, 126 (25%) patients underwent redo AF ablation. Among them, we enrolled patients who underwent PVI-alone (N=69), or PVI-plus left atrial (LA) linear ablations (LA roof and mitral isthmus) (N=46) during the index ablation.

Results:
In the previous PVI-alone group, electrical PV gaps were observed in 38 (57%) patients. In the previous PVI-plus group, 19 (41%), 10 (22%), and 11 (24%) patients had electrical gaps in the PVs, LA linear lines, or both, respectively. During the redo session, 19 atrial tachycardias (ATs) were observed/induced in 15 patients. ATs were more frequently observed in the PVI-plus group than in the PVI-alone group (23.9% vs. 5.8%, p=0.005). While 7 ATs were not associated with gaps, 2 were related to PV gaps, and 10 were related to gaps in the linear lesions. In the redo AF ablation, PVI was re-completed in all patients, and any induced ATs were eliminated by additional ablation. During a median follow-up of 32 months post-redo, patients with gaps had a lower clinical recurrence rate than those without (44.3 vs. 47.2%, log-rank p=0.033). However, the Cox regression analysis revealed that AF recurrence post-redo was associated only with PV gaps, and not with linear ablation gaps (hazard ratio, 0.57; 95% confidence interval, 0.32–0.99; p = 0.049).

Conclusions:
In redo AF ablations, electrical gaps were more prevalent in patients who underwent extensive ablation during the index procedure. While all gaps during redo were potentially arrhythmogenic, PV gaps alone were associated with AF recurrence after redo AF ablation.
Abstract 4137965: D-dimer as a 5-year predictor of death in females admitted with chestpain of suspected coronary origin surpasses that of males.
Authors: Nilsen Dennis , Brugger-Andersen Trygve , Aarsetoey Reidun , Ueland Thor , Michelsen Annika , Aukrust Pal , Poenitz Volker , Staines Harry , Grundt Heidi
Published: November 2024

Background:
D-dimer (DD) and fibrin monomer (FM) are endstage markers of activated coagulation and reflect prothrombotic states, and α2-antiplasmin (SERPINF2 -SF2) is the main inhibitor of fibrinolysis at the level of plasmin. Women may experience a higher rate of morbidity and mortality compared to men following a myocardial infarction (MI). We present the prognostic potential of DD, FM and SF2 in females as compared to males during 5 years follow-up in a population admitted with chest pain of suspected coronary origin.

Methods:
A total of 871 consecutive patients with a median age of 72.6 years (females 77.3, males 69.1) were admitted in the study. Of these, 386 were diagnosed with an acute MI based on Troponin-T (TnT) levels >50 ng/L. Stepwise Cox regression models, applying normalized continuous log
e
/SD values, were fitted for the biomarkers with total mortality within 5 years as the dependent variable.

Results:
Death was recorded in 246 patients; 34.4% females vs. 27.2% males (Chi-squared test p-value = 0.02). Blood samples were available for analysis of DD, FM and SF2 in 820, 810 and 846 patients, respectively. Females had a signficantly higher mean of DD (p<0.0001) and FM (p=0.0020) than males and SF2 did not differ (p=0.0825).

In the univariate analysis, a highly significant association between DD and total death was observed in both sexes (p<0.001). However, after adjusting for confounders in the multivariable analysis, the associations remained significant in females but not in males, with an HR of 1.62 (95%CI 1.36 – 1.93), p<0.0001 vs. 1.16 (95%CI 0.98 - 1.39, p=0.094, respectively, (p for interaction <0.001).

Similar findings were noted in the multivariable analysis of FM with HR 1.46 (95%CI 1.19 – 1.80), p=0.0003 in females vs. 1.12 (95%CI 0.93 -1.35), p=0.22 in males (p for interaction 0.056).

In the univariate analysis, SF2 was not associated with all-cause mortality; p=0.56 in females vs. p=0.83 in males, and remained essentially unchanged after adjustment; p=0.84 vs. HR 0.92 (95%CI 0.78 – 1.09). p=0.35 in males, yielding a p=0.36 for interaction.

Conclusion:
Activated endstage coagulation was associated with total death at 5 years FU in females admitted with chest pain of suspected coronary origin, whereas plasmin inhibition was not. A significant p-value for interaction between the two sexes indicates that the prognostic value of DD surpasses that of men.