bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4146930: Reported Stress Level is Associated with Cardiovascular Health in Young Adults – An Electronic Health Record Study of Nearly 1.4 Million Individuals
Authors: Ortiz Robin , Heffron Sean
Published: November 2024

Background:
Young adulthood (19–39 years) is the life stage of greatest declines in cardiovascular health (CVH). It is hypothesized that this decline may be related to competing demands (e.g., stressors) of this period of the lifecourse such as work and child-rearing. The AHA’s Life’s Essential 8 CVH framework identifies the scored domains (behavioral and clinical factors), as needing to be contextualized by the important construct of psychological health (including stress). However, scarce data are available to assess the relationship between CVH and reported stress – especially among YA.

Purpose:
The current study aims to be the first to use Cosmos electronic health record (EHR) data to assess the relationship between YA CVH and reported stress in a nationally representative, very large sample of YAs.

Methods:
Cosmos is a platform hosting de-identified Epic EHR data on >250 million patients. We assessed Cosmos data from May 2022 through April 2024 to identify all YAs with reported stress data (5-point scale from “not at all” to “very much”). We then compared trends of each CVH metric across stress categories.

Results:
1,397,375 individuals 19 - 39 years of age had reported stress data available. The sample was 62% White, 17% Black, 4% Asian, 12% Hispanic, and 63% female. Generally, stress levels were stable across YA age groups (Figure 1). For lifestyle behavior related domains (physical activity (PA), smoking, and BMI), the prevalence of “poor” CVH scores (worst categorization) increased in YA as reported stress amount increased (Figure 2). Prevalence of “poor” scores in clinical metrics (BP, HbA1c, nonHDL-C) were not associated with stress.

Conclusion:
In a very large sample of YA, greater reported stress was associated worse CVH for the behavioral domains of PA, smoking and BMI. Interventions aimed at reducing stress in YA may have the added benefit of improving CVH.
Abstract 4146939: Impact of Diagnosis Timing (Early vs Late) on Atrial Fibrillation Progression in Patient with New Onset Atrial Fibrillation During COVID Illness
Authors: Cutler Michael , Bair Tami , Knight Stacey , Packer Douglas , Anderson Jeffrey , Knowlton Kirk , May Heidi
Published: November 2024

Background:
New onset AF during acute illness has a high rate of AF recurrence within 5-yr. However, little is known about AF progression in patients with new onset AF during COVID illness. It is also unknown whether the time of COVID diagnosis (early vs late) impacts AF progression. More specifically, did the potentially different immune and inflammatory responses during early vs late COVID produce structural and electrical cardiac remodeling that would increase the likelihood of AF progression.

Objective:
We sought to compare AF progression in patients with new onset AF during early vs late COVID and hypothesized that early COVID was associated with increased AF progression compared to late COVID.

Methods:
From Apr 2020 to Feb 2024, patients receiving a SARS-2-CoV test without a history of AF with new onset AF and at least 3-mo of follow up were included (N=11,767). Patients were subdivided based on pos vs neg SARS-2-CoV test and time of diagnosis. Early COVID diagnosis (n=3052) included Apr 2020-Aug 2021 and late COVID (n=8715) included Sep 2021-Feb 2024. AF progression endpoints at 3-, 6- and 12-mo included AF hospitalization, AF emergency department (ED) visit, cardioversion and AF ablation.

Results:
Patients with late COVID were more likely females with hypertension, coronary artery disease and hyperlipidemia compared to early COVID patients. At 3- and 6-mo follow-up there was no difference in AF progression between the early and late COVID groups for any endpoint. In contrast, at 12-mo follow up there was in increase in late diagnosis group AF ED visits (11% vs 7.6%,
p
<0.0001) and a trend toward more AF hospitalizations (6.3% vs 4.1%,
p
=0.07). There was no difference in cardioversions or AF ablations between the groups at 12-mo. Finally, patients with an early COVID trended to be less likely to undergo AF ablation (3.9% vs 5.6%,
p
=0.14) and have an AF hospitalization (4.1% vs 6.3%,
p
=0.06) at 12-mo than new onset AF patients during the same time without COVID. There was no difference in AF progression between COVID pos and neg patients in the late COVID group.

Conclusions:
These findings demonstrate that there is no significant difference in AF progression in patients with new onset AF during COVID when stratified by timing of diagnosis. As such, our data do not support the hypothesis that early COVID resulted in more significant structural or electrical cardiac remodeling that would increase the likelihood of AF progression.
Abstract 4146968: The Impact of Weight Loss Following Bariatric Surgery on Regression in Cardiovascular-Kidney-Metabolic Syndrome
Authors: Aryee Ebenezer , Ozkan Bige , Benotti Peter , Chu Xin , Wood G Craig , Rajgopal Singh Radhika , Hoogeveen Ron , Gerstenblith Gary , Selvin Elizabeth , Coresh Josef , Ndumele Chiadi
Published: November 2024

Background:
Cardiovascular-Kidney-Metabolic (CKM) syndrome reflects the interrelatedness of cardiovascular, kidney, and metabolic disease, with excess/dysfunctional adiposity as the predominant etiology. The CKM staging framework facilitates assessment of progression, as well as regression, of CKM syndrome stages. However, the impact of intentional weight loss on CKM stage regression has not been quantified.

Methods:
We prospectively evaluated 360 bariatric surgery patients in the Geisinger Obesity Institute Registry free of cardiovascular disease. Data were collected pre-operatively, and 6-18 months post-operatively. CKM syndrome stage was defined as Stage 0: no CKM risk factors; Stage 1: excess/dysfunctional adiposity (body mass index >= 25kg/m
2
or fasting blood glucose [FBG] 100-125mg/dL); Stage 2: metabolic risk factors (high blood pressure [>= 130/80mmHg], diabetes [FBG >= 126mg/dL], hypertriglyceridemia [>= 135mg/dL]), or chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] 30 - <60mL/min/1.73m
2
); and Stage 3: moderate-to-severely elevated high-sensitivity cardiac troponin I levels (>= 4 ng/L in women or >= 6 ng/L in men) or very high-risk CKD (eGFR < 30 mL/min/1.73m
2
). We compared the distribution of CKM stages pre- and post-surgery, and used logistic regression and cubic splines to assess the association of weight loss with odds of regressing to a lower CKM syndrome stage over time.

Results:
The mean age was 46 years (83% women, 95% White, mean BMI 46 kg/m
2
). On average, participants lost 28% of their baseline weight. During follow-up, there was a decrease in the proportion with CKM stage 3 (20% to 12%) and stage 2 (65% to 41%), with an increase in stage 1 (15% to 42%). CKM Stage 0, non-existent pre-surgery, was seen in 5% of participants post-surgery. Overall, 45% regressed in CKM syndrome stage (Panel A). In logistic regression, there was a linear relationship between weight loss and odds of CKM stage regression (Panel B), with each 10% greater weight loss associated with an OR of 1.91 (95% CI 1.45-2.50) for CKM stage regression.

Conclusion:
Weight loss is strongly linked to CKM stage regression, underscoring the role of intentional weight loss in improving CKM health.
Abstract 4146982: A Rationally Designed Cardioprotective Nanoparticle to Treat Chemotherapy-Induced Cardiotoxicity
Authors: Khatun Zehedina , Kung Andrew , Boukhalfa Asma , Thompson Anna-Lee , Weng Sydney , Wei Lan , Meng Lin , Martin Gregory , Mekkaoui Choukri , Blanton Robert , Baleja James , Yang Vicky , Yuan Hushan , Chen Howard
Published: November 2024

Introduction:
Chemotherapy-induced cardiotoxicity is a growing clinical challenge lacking effective FDA-approved interventions to delay the onset of heart failure. Lysosomal dysfunction is a hallmark of a myriad of cardiovascular diseases, including doxorubicin (Dox)-induced cardiotoxicity. We hypothesize that maintaining cardiomyocyte (CM) lysosomal pH can mitigate Dox-induced cardiac dysfunction and presents a viable cardioprotective strategy for translation.

Methods:
FDA-approved PLGA polymer composed of lactic and glycolic acids was chosen to modulate lysosomal pH due to biosafety and ease of chemical modifications. PLGA was covalently labeled with near-infrared fluorescent peptides to enhance cellular uptake and facilitate tracking in vivo. PLGA was formulated into nanoparticles of 100 nm and characterized by electron microscopy, NMR and absorbance spectroscopy. In H9C2 rat CMs co-treated with 5 μM of Dox +/- 1 mg/ml of PLGA, we measured PLGA uptake by FACS, cell viability by MTT, lysosomal pH by OG-514, and autophagy by western blot. PLGA’s impact on breast cancer cell viability was measured by MTT. In C57Bl/6 wildtype mice challenged with Dox (15 mg/kg, i.p.) +/- co-injection of PLGA (10 mg/kg, i.v.), myocardial PLGA uptake at 4 hours and apoptosis (by Annexin V) at 24 hours were assessed by direct imaging. Echocardiography to assess cardiac function was performed in a separate cohort of mice injected with weekly Dox (4 mg/kg, i.p.) +/- PLGA (10 mg/kg, i.v.). Moreover, PLGA biocompatibility was evaluated in 3 healthy beagle dogs by echocardiography and blood chemistry.

Results:
In Dox-treated murine CMs, PLGA significantly improved survival by restoring lysosomal acidity and autophagy, a key homeostatic process. No protective effect was observed with non-acidifying control polymer. PLGA also did not alter viability in human breast cancer cells (MCF7, MDA-MB-231) treated with Dox. When injected in mice, PLGA fully permeated the myocardium within 4 hours, significantly reduced Dox-induced apoptosis by 24 hours, and significantly improved cardiac function 4 weeks after Dox injection. In healthy canines, PLGA can be safely administered, supporting further clinical trials.

Conclusions:
PLGA represents a novel class of translatable cardioprotective therapeutic that acidifies lysosomes, restores autophagy, mitigates CM apoptosis, and enhances cardiac function. PLGA holds translational potential to mitigate lysosomal dysfunction and treat cardiovascular disease.
Abstract 4146993: Anthracycline-based Chemotherapy in A Patient with Breast Cancer and Left-Ventricular Hypertrabeculation
Authors: Rahme Serena Joseph , Cathcart-Rake Elizabeth , Giudicessi John , Herrmann Joerg
Published: November 2024

Introduction:
Anthracyclines (AC), a class of chemotherapeutic drugs, are used to treat various cancers, including breast cancer (BC). However, AC cause dose-dependent cardiac toxicity. Practice guidelines list pre-existing cardiomyopathy as a risk factor for cancer therapy-related cardiac dysfunction (CTRCD), but there is a lack of data on cardiotoxicity risk in patients with left ventricular (LV) hypertrabeculation without LV hypertrophy/dilation. We present a patient with LV hypertrabeculation who developed LV dysfunction after AC chemotherapy for BC.

Description of Case:
A 55-year-old woman diagnosed with multicentric invasive ductal carcinoma (IDC) of the right breast, stage IIA (cT3 cN1 cM0), grade 2, ER+/PR+/HER2-, was treated with neoadjuvant Paclitaxel for 3 months. Before AC-based chemotherapy, stress cardiac MRI due to residual post-COVID-19 dyspnea showed LV hypertrabeculation with a non-compacted/compacted ratio of 2.3, LVEF 56%, and no delayed enhancement. Transthoracic echocardiography (TTE) reported an LVEF of 52% with GLS of -17%. The patient's electrocardiogram (ECG) showed normal sinus rhythm, and NT-pro BNP levels were <20 pg/mL. Genetic testing identified a rare variant in MYH7-encoded myosin heavy chain 7 (p.Arg941Leu-MYH7). She had no cardiovascular (CV) risk factors or family history of CV disease. She then underwent 4 cycles of Doxorubicin (cumulative dose 232.2 mg/m2) and Cyclophosphamide, followed by bilateral mastectomy and adjuvant radiotherapy (5000 cGy in 25 fractions). One year after chemotherapy, follow-up TTE showed LVEF decreased to 45% with GLS of -17%. The patient’s ECG remained normal, and NT-pro BNP levels were <36 pg/mL. Despite an LVEF decline, not all criteria for CTRCD were met, suggesting a gene-environment interplay between her chemotherapy and pre-existing MYH7-mediated non-dilated LV cardiomyopathy (NDLVC) with hypertrabeculation. The patient has remained without symptoms of heart failure and is currently taking Letrozole 2.5 mg daily.

Discussion:
This case offers a unique perspective on a BC patient treated with AC chemotherapy, who has a possible MYH7-mediated NDLVC with hypertrabeculation, and who experienced an LVEF decline of indeterminate significance. While the association of her possible NDLVC with hypertrabeculation is uncertain, the safety of AC in patients with isolated hypertrabeculation or NDLVC with hypertrabeculation, as introduced by the 2023 ESC cardiomyopathy guidelines, remains to be defined.
Abstract 4146994: Electronic Health Record Based Clinical Decision Support Increases Guideline-Directed Medical Therapy Initiation or Dosage Intensification in Patients with Heart Failure with Reduced Ejection Fraction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Motamed Mehras , Nunes Jairo , Upagupta Chandak , Shi Daniel , Udell Jacob
Published: November 2024

Introduction:
Guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) remains underprescribed despite overwhelming evidence of clinical benefit. Electronic health record (EHR)-based clinical decision support (CDS) tools provide healthcare providers with evidence-based recommendations and reminders within the electronic health record system. EHR-based CDS tools offer an innovative and economical strategy to enhance GDMT prescription rates.

Hypothesis:
We hypothesized that EHR-based CDS is associated with increased GDMT initiation or dosage intensification in patients with HFrEF.

Methods:
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) published from inception to May 2024 on four databases: PubMed, Embase, CENTRAL, and MEDLINE. We included RCTs that assessed the impact of EHR-based CDS on GDMT initiation or dosage increase in patients with HFrEF. The primary outcome was a composite of GDMT initiation or dosage increase. Random effects meta-analysis was performed by Review Manager version 5.4 software. I
2
statistics was used to assess heterogeneity.

Results:
Out of 6716 retrieved studies, 5 RCTs involving 4881 patients met inclusion criteria. The inter-rater agreement was excellent (κ = 0.911). The primary outcome showed an overall effect size of 1.38 (95% CI: 1.00-1.91, P = 0.05; I
2
= 86%). Adjusted relative risk was not reported for most studies, and hence this data could not be provided. Visual inspection of the funnel plot was balanced.

Conclusions:
This meta-analysis indicates that EHR-based CDS tools show a potential to increase initiation of GDMT or increase GDMT dosage in HFrEF patients. Further investigation is required to validate these findings due to significant heterogeneity and limited included studies.
Abstract 4147006: Relationship between Triglyceride-Glucose Index, Subclinical Myocardial Injury, and Cardiovascular Mortality in NHANES III
Authors: Ononye Chuka , Bapat Santul , Chebrolu Sneha , Pruitt Zachary , Soliman Elsayed , Kazibwe Richard
Published: November 2024

Background:
Subclinical myocardial injury (SCMI) and the triglyceride-glucose index (TyG), a marker for insulin resistance, are each linked to cardiovascular (CV) mortality. The impact of both SCMI and TyG on CV mortality is unclear.

Objective:
To investigate the relationship between TyG, SCMI, and CV mortality.

Methods:
This study utilized data from the third National Health and Nutrition Examination Survey (NHANES-III) including participants without cardiovascular disease (CVD). Baseline TyG was calculated as ln(fasting triglyceride level [mg/dL] × fasting plasma glucose [mg/dL]/2). High TyG was defined as ≥75th percentile, and low TyG as <75th percentile. SCMI was identified by an electrocardiogram (ECG) cardiac infarction injury score ≥10. CV mortality data was sourced from the National Death Index. Associations of TyG with SCMI were analyzed using multivariate logistic regression, and Cox proportional hazards models assessed the individual and combined associations of TyG and SCMI with CV mortality.

Results:
Of 7,082 participants (mean age 59.3±13.4 years; 52.8% women; 49.4% White), 1,775 (25.1%) had high TyG and 1,860 (26.3%) had SCMI. High TyG was associated with higher odds of SCMI (odds ratio (OR): 1.38, 95% CI: 1.21–1.57, p<0.0001) and each unit increase in TyG corresponded to increased SCMI risk (OR: 1.27, 95% CI: 1.16–1.39, p<0.0001). High TyG and SCMI were linked to 32% and 38% higher CV mortality risk, respectively. Participants with both high TyG and SCMI had a significantly higher risk of CV mortality (Hazard ratio (HR): 1.78, 95% CI: 1.46–2.19) compared to those with low TyG and no SCMI
(see Table)
. The interaction between SCMI and TyG in the fully adjusted Cox Model 2
(see Table)
was not statistically significant (p=0.45).

Conclusions:
In NHANES III adults without CVD, TyG was associated with SCMI. Both high TyG and SCMI independently increased CV mortality risk, with the greatest risk observed in individuals with both conditions. Further research is needed to evaluate the effectiveness of these markers in CVD risk assessment and explore interventions to mitigate this risk.
Abstract 4147011: Ticagrelor Monotherapy Following Short Dual Antiplatelet Therapy versus 12-Month Dual Antiplatelet Therapy after Percutaneous Coronary Intervention for STEMI: A Meta-Analysis of Randomized Controlled Trials
Authors: Joseph Meghna , Murali Krishna Mrinal , Ezenna Chidubem , Goldsweig Andrew
Published: November 2024

Introduction:
Guidelines recommend dual antiplatelet therapy (DAPT) for 12 months following percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). However, prolonged DAPT may increase bleeding risk. Monotherapy with the potent P2Y12 inhibitor ticagrelor after short DAPT offers a promising strategy to balance thrombotic and bleeding risks.

Objective:
To compare outcomes of short DAPT (≤3 months) followed by ticagrelor monotherapy until 12 months vs. 12-month DAPT in patients undergoing PCI for ACS.

Methods:
We systematically searched PubMed, Scopus, and Cochrane Central databases for studies comparing short DAPT followed by ticagrelor monotherapy vs. 12-month DAPT following PCI. Outcomes of interest included net adverse clinical events (NACE), major adverse cardiovascular/cerebrovascular events (MACCE), and any bleeding at 12 months post-PCI. Statistical analysis was done using R software. Random effects models were used to generate risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I
2
statistics. Analysis followed the PRISMA guideline.

Results:
The systematic review identified 4 randomized controlled trials including 5,293 patients. Ticagrelor monotherapy was used in 2,667 (50.38%) patients. At 12 months, NACE (RR 0.81; 95%CI 0.57-1.14; p=0.227; I
2
=45%), MACCE (RR 1.11; 95%CI 0.86-1.42; p=0.415; I
2
=3%), and any bleeding (RR 0.68; 95%CI 0.46-1.01; p=0.055; I
2
=34%) were comparable between the two groups.

Conclusion:
After PCI for STEMI, short DAPT for ≤3 months followed by ticagrelor monotherapy was non-inferior to 12-month DAPT in terms of NACE, MACCE, and bleeding. Ticagrelor monotherapy following short DAPT may be considered for STEMI patients after PCI.
Abstract 4147018: Predictors of Clinically Meaningful 1-Year Health Status Improvements Following Endovascular or Surgical Revascularization: Insights from the BEST-CLI Trial
Authors: Smolderen Kim , Menard Matthew , FARBER Alik , Rosenfield Kenneth , Strong Michael , Doros Gheorghe , Goodney Philip , Romain Gaelle , Cleman Jacob , Scierka Lindsey , Mena-Hurtado Carlos
Published: November 2024

Background:
Understanding patient factors associated with successful clinically meaningful health status results after undergoing endovascular or surgical revascularization for chronic limb threatening ischemia (CLTI), will enable targeted allocation of care resources. We examined predictors of meaningful improvements in 1-year health status following endovascular or surgical revascularization 1 year after the procedure.

Methods:
We applied distribution-based (0.5 standard deviation of baseline health status scores) minimally clinically important difference (MCID) thresholds to 1-year health status change scores derived from a pooled cohort of the endovascular and surgical arms for the Best Endovascular versus Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial. The trial was conducted during 2014-2019 and enrolled patients with CLTI from 150 international sites. Patients completed the peripheral artery disease (PAD)-specific VascuQol prior randomization and 1 year following randomization. Multivariable logistic regression models (improved vs. remained the same/worsened) for 1-year VascuQol changes were constructed, including demographic and clinical factors. Cubic splines were explored for presenting baseline VascuQol health status scores.

Results:
A total of 1,533 patients were included, (71.9% male, mean age 66.9 ± 9.7 years). Absence of diabetes, history of claudication, and lower Wifi stage was more likely to be associated with successful health status response at 1 year (R
2
=0.77). Baseline presenting health status was associated with the odds of achieving a successful health status response, with those presenting with lower baseline scores (VascuQol score <3), having a higher odds of a successful PAD-specific health status response. Type of revascularization (endo vs. surgery) was not associated with successful health status response (
Figure
).

Conclusion:
Diabetes status, claudication history, and Wifi staging are important factors to evaluate when discussing the potential for a successful health status response following endovascular or surgical revascularization. Overall, those who present with more impacted health status, stand to benefit the most, regardless of revascularization type.
Abstract 4147022: Aligned Mechanical Tension Improves Electrophysiology of iPSC-Derived Engineered Heart Tissue
Authors: Ramahdita Ghiska , Chau Thao , Bhakta Riya , Pobee Charlene , Jiang Huanzhu , Genin Guy , Huebsch Nathaniel
Published: November 2024

Introduction:
Cardiomyocyte alignment increases over time during normal heart development. This alignment is associated with aligned mechanical tension and plays a key role in electromechanical function of the tissue. Myocardial disarray, in which the alignment is disrupted, is a hallmark of cardiomyopathy. This structural disarray is often accompanied by electrophysiological disfunction. Prior work, including ours, suggests that sodium channel function in particular is enhanced in aligned 3D tissues engineered from human induced pluripotent stem cells (iPSC). We hypothesized that cardiomyocyte alignment in 3D tissue could lead to enhanced sodium channel function by improving sodium channel expression.

Methods:
To test our hypothesis, we developed a micro-engineered heart tissue (μEHT) platform in which
total
mechanical tension could be decoupled from
cardiomyocyte alignment
. The μEHTs were cultured for at least 7 days in either a 4-post configuration to induce high uniaxial tension (expected to cause cardiomyocyte alignment), or 8-post configuration to induce multiaxial tension (expected to cause cardiomyocyte disarray; Fig. 1a). Optocardiography was carried out to study calcium dynamics (GCaMP6f reporter) and action potential waveforms (voltage-sensitive dye, BeRST-1), in heart muscle engineered from induced pluripotent stem cells (iPSC) derived cardiomyocytes. A sodium channel blocker, Saxitoxin, was added for drug response study. Sodium channel expression was assessed with Western blot and immunofluorescence analysis.

Results:
4-post mEHTs had a lower action potential excitation threshold and faster phase-0 in action potential duration, which suggests improved electrophysiology compared to 8-post EHT. Calcium dynamics data, however, did not show significant difference. Additionally, 4-post EHTs exhibited a more pronounced response to Saxitoxin. Immunofluorescence shows a trend of higher colocalization of NaV1.5 and N-cadherin in the area with high predicted uniaxial tension and cardiomyocyte alignment. Western analysis suggested that aligned mechanical tension led to higher overall expression of Na
V
1.5, the cardiac sodium channel (paired t-test n=3, p=0.0315).
Abstract 4147046:

Trends in Stroke-Related Mortality in Hypertensive Patients Aged 65 and Older in the United States: Insights from the CDC WONDER Database
Authors: Naveed Muhammad Abdullah , Ali Ahila , Neppala Sivaram , KASHAN MUHAMMAD , Iqbal Rabia , Azeem Bazil , Omer Rehan Muhammad , Ashfaque Faiza , Ansari Huzaifa , Chigurupati Himaja Dutt , Paul Timir
Published: November 2024

Background:
Stroke is one of the leading causes of death for older individuals with hypertension. This research investigates the variations in stroke mortality rates and trends among 65-year-old hypertension patients in the US from 2000 to 2020.

Methods:
The CDC WONDER database's mortality data from 2000 to 2020 was used for a retrospective analysis. Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) were used to evaluate trends and produce age-adjusted mortality rates (AAMRs) per 100,000 people. Data was stratified by year, sex, race/ethnicity, and geographical regions.

Results:
Between 2000 and 2020, 598,341 deaths among individuals 65 years of age or older in the United States were related to stroke due to hypertension. Most occurred in nursing homes/long-term care facilities (36.7%). The overall AAMR for stroke in hypertension-related deaths dropped from 86.6 in 2000 to 51.8 in 2020, with an AAPC of -2.86 (95% CI: -3.18 to -2.61, p < 0.000001). Between 2000 and 2012, the AAMR had a considerable reduction (APC: -2.30, p < 0.000001). Subsequently, from 2012 to 2018, there was a more dramatic decrease (APC: -6.85, p < 0.000001) than a notable rise (APC: 6.45, p = 0.024) from 2018 to 2020. Older women had higher AAMRs than older men (women: 66.5; men: 60.1). Both sexes experienced decreases, with the decline more prominent in women (women: AAPC: -3.20, p < 0.000001; men: AAPC: -2.22, p < 0.000001). There were notable racial differences: Black people had the highest AAMRs (31.0), followed by White people (21.8), American Indians and Alaska Natives (18.6), Asians and Pacific Islanders (12.9), and Hispanics (12.5). All racial groups experienced decreases in AAMRs, most pronounced in Asians (AAPC: -4.62, p < 0.000001). Geographically, Massachusetts had the lowest (36.3), and Mississippi had the highest (117.7) AAMRs. The Western region had the highest average AAMR (71.8), while nonmetropolitan areas exhibited higher AAMRs than metropolitan areas (nonmetropolitan: 25.9; metropolitan: 20.7).

Conclusion:
The study uncovers significant variations in mortality rates among elderly individuals in the US due to stroke and hypertension. The recent uptick emphasizes the necessity for targeted efforts to tackle these disparities and improve the health outcomes of affected communities.
Abstract 4147047: Assessing Knowledge, Attitudes, and Practices Regarding the American Heart Association’s Framework for Cardiovascular Health in Pediatrics
Authors: Ortiz Robin , Chan Debra , Nita Abigail , Heffron Sean , Nagpal Nikita , Duh-Leong Carol
Published: November 2024

Background:
Despite emphasis on establishing cardiovascular health (CVH) early in life with an intergenerational approach, it remains unknown if child health professionals are aware of the American Heart Association (AHA) framework and recommendations.

Methods:
Survey design included: 1) Likert scales of AHA CVH framework awareness (Simple 7 (LS7) and/or Life’s Essential 8 (LE8), 2) a knowledge assessment, and 3) introduction of the LE8 framework with mixed methods assessment of perceived attitudes and practice implications. The survey was distributed via professional organizations (American Academy of Pediatrics, Regional Academic Pediatric Association, National Med-Peds Residents Association) to members with a gift card incentive and snowball sampling approach. Response rate (RR) reporting was limited by organizational dissemination with snowball sampling, but was calculated by number of opened surveys (link clicks). Descriptive statistics summarized results.

Results:
There were 221 respondents to the awareness items with 169 surveys fully completed (91.7, and 70.1% of opened surveys), from across all US regions (34 states + Puerto Rico), who were mainly senior residents or practicing physicians in general pediatrics or Med-Peds (33±7yrs, 68% female). Most were “not aware at all” of either framework (64.5, 68%,
Figure
). Mean knowledge score was 40% (3.2/8). While majority (56.1%) reported increased need to clinically address CV risk over time, only 37.3% were comfortable addressing risk/counseling in pediatric practice (most often diet, physical activity). Over half found the framework valuable for pediatric patients and adult caregivers (54.1, 55.2%,
Figure
) and ~¾ reported that knowledge of it would change their practice, including for patient education, risk stratification, and sub-specialty engagement. Nearly all (92.4%) felt a joint AHA-Pediatrics organization CVH collaboration (e.g., task force, statement) would be valuable.

Conclusions:
Most pediatric professionals surveyed reported no awareness of the AHA CVH framework, but valued its utility in working with children and caregivers in practice, highlighting a need for engagement of child health professionals in LE8 dissemination and implementation.
Abstract 4147067: Acute Exposure to High PM
2.5
Levels Increases the Risk of Late All-Cause Mortality in Patients with STEMI
Authors: Fathieh Sina , Tran Hao , Faour Amir , Pahn Reece , Long Mitchell , Tam Gladys , Figtree Gemma , Negishi Kazuaki , French John
Published: November 2024

Background:
Short-term exposure to ambient air pollution, especially particulate matter smaller than 2.5 microns in diameter (PM
2.5
), is associated with an increased risk of acute coronary syndrome and is identified as the leading modifiable cause of cardiovascular mortality in the long term. In this study, we set out to examine the effect of acute exposure to high levels of PM
2.5
(≥12 μg/m
3
) on long-term mortality risk of ST-elevation myocardial infarction (STEMI) patients.

Methods:
From June 2010 to October 2021, 1,553 patients at Liverpool Hospital in Sydney met the 4th Universal Definition of MI criteria for STEMI. The average daily maximum PM
2.5
was measured using publicly available land-based air quality monitors in the catchment area. Mortality risk between the two groups was compared using a Kaplan-Meier plot and further assessed using the Cox regression model.

Results:
915 STEMI patients presented on days with maximum PM
2.5
≥12 μg/m
3
. These patients had a significantly increased risk of late all-cause mortality with a hazard ratio of 3.08 (CI= 2.01-4.71, p<0.001) compared with those with lower PM
2.5
level exposures. Each 10-unit increase in PM
2.5
exposure was associated with a 10% (p=0.002) higher risk of late mortality.

Conclusions:
Patients presenting with STEMI on polluted days are at increased risk of late all-cause mortality, which may be due to increased inflammatory response and myocardial injury at the time of cardiac insult. This finding warrants a more diligent acute care and long-term follow-up strategy for this group of vulnerable patients.
Abstract 4147071: Lupus Mitral Valve Disease Masquerading as an Absent Posterior Mitral Valve Leaflet
Authors: DiGregorio Helene , Khan Madiha , El Hajj Elia , Dhore Aneesh , Yao David , Reul Ross , Faza Nadeen
Published: November 2024

Introduction/Background:
Marantic endocarditis and valvulitis are cardiovascular manifestations of autoimmune disease that can be challenging to diagnose.

Case Presentation:
A 23-year-old female with SLE presented with brief episodes of intermittent left eye vision loss and left sided weakness. She also reported fevers, a malar rash, and new onset dyspnea on exertion.

Serologic work-up was consistent with an SLE flair. MRI of the brain/orbits demonstrated two acute infarcts in the frontal and parieto-occipital lobes. CTA head and neck did not show any large vessel vasculitis. Transthoracic echocardiography showed thickening of the mitral valve (MV) leaflets, with moderate MR and an elevated MV gradient of 11 mm Hg. The posterior leaflet was not visualized, concerning for absent or hypoplastic posterior leaflet. A transesophageal echocardiogram was performed and showed severe thickening of posterior mitral leaflet with restricted motion and shortening secondary to extensive thrombus burden. In addition, there was evidence of thrombus at the tip of the anterior MV leaflet. The patient was managed with high dose steroids and warfarin for SLE flair and marantic endocarditis, respectively.

Two months later, she presented with amaurosis fugax. Cardiac MRI showed thickened MV leaflets with delayed enhancement along the posterior leaflet and MV annulus consistent with an organized thrombus. After multidisciplinary discussion, the patient underwent surgical MV replacement with a bioprosthetic valve. Intraoperative evaluation revealed severely thickened MV leaflets with fused commissures. In addition, there was fusion of the posterior leaflet and lateral side of the anterior leaflet to the papillary muscles as a result of thickened and shortened chordae. These findings were believed to be due to inflammatory changes involving the MV apparatus. Surgical pathology confirmed the diagnosis of valvulitis. The patient has done well post operatively.

Conclusion:
Valvulitis and marantic endocarditis can have devastating consequences if not treated promptly. Use of multimodality imaging can aid in the diagnosis. Multidisciplinary discussion is critical in achieving desired clinical outcomes.
Abstract 4147117: Impact of Heavy Metal Exposure On Cardiovascular Disease Mortality
Authors: Younas Hafiz Muhammad Waqar , Thyagaturu Harshith , Chobufo Muchi Ditah , Patel Kunal , Valand Hardik , Ludhwani Dipesh , Padala Vikram , Mubeen Hafiz Khizer , Upreti Prakash , Younas Hafiz Muhammad Umair , Gonuguntla Karthik
Published: November 2024

Background:
Cardiovascular disease (CVD) is the primary cause of mortality worldwide, and heavy metal exposure, including lead (Pb), cadmium (Cd), and mercury (Hg), significantly impacts this global burden of disease. Heavy metal-related cardiovascular toxicity results from their ability to induce oxidative stress, inflammation, endothelial dysfunction, and dysregulation of lipid metabolism. We aim to investigate the cardiovascular disease mortality associated with high blood levels of Pb, Cd, and Hg.

Method:
Using the 1999–2018 National Health and Nutrition Examination Survey (NHANES) data, we examined the association of blood Pb, Cd, and Hg levels with CVD mortality. Pb, Cd, and Hg levels were transformed into quartiles. Mortality hazard ratios were calculated using Cox proportional multivariate regression models adjusting for confounders identified by way of univariate analysis and from literature. Survival across quartiles of Pb, Cd, and Hg levels are depicted using K-M curves. Survival probabilities were compared using KM curves. All analyses were conducted using STATA version 17.0

Results:
The study population comprised 55,081 participants spanning over 20-years period, among whom 2401 (4.36%) experienced CVD related to Pd, Cd, and Hg exposure. Of the participants, 48% were male, with the majority being White participants, followed by Hispanic and Black participants. Most participants (82.4%) had a college education or higher, 53.2% were from high-income families, and 91.3% did not report a history of CVD. Mean levels of Pb, Cd, and Hg were 0.51 µg/L, 1.62 µg/L, and 1.56 µg/L, respectively. Significant differences in CVD mortality were observed between the toxic metal exposure group and those without exposure. The mortality group was associated with a higher prevalence of diabetes, higher BMI, CVD history, and higher levels of Cd and Pb but lower Hg levels.

Conclusions:
In conclusion, our study revealed a higher prevalence of cardiovascular mortality in individuals with elevated blood Pb and Cd levels. In contrast, those with higher blood Hg levels exhibited reduced cardiovascular mortality
Abstract 4147142: Inhaled Benzene Exacerbates Atherogenesis and Compromises Plaque Composition and Stability
Authors: Zelko Igor , Taylor Breandon , Malovichko Marina , McFall Samantha , Conklin Daniel , Chen Hong , Barati Michelle , Merchant Michael , srivastava sanjay
Published: November 2024

Background:
Benzene is a ubiquitous environmental pollutant abundant in automobile exhaust, cigarette smoke, forest fires, and present in several household products. It is ranked # 6 on Agency for Toxic Substances and Disease Registry (ATSDR) priority list, however, little is known about its effect on cardiovascular disease, especially atherosclerosis.

Hypothesis:
Inhaled benzene induces atherogenesis by increasing vascular inflammation in LDL receptor Knockout (LDLR-KO) mice.

Methods:
Male LDLR-KO or apoE-KO mice were exposed to HEPA-filtered air or benzene (1.0 or 10.0 ppm, 6h/day, 5 days/week) for 24 weeks and maintained on Western diet for the last 12 weeks of exposure. Atherosclerotic lesion composition and nature were determined by liquid chromatography-mass spectrometry (LC-MS), single nuclei RNA sequencing (snRNAseq), and Cytometry by time of flight (CyTOF).

Results:
Inhaled benzene exposure significantly increased lesions in the aortic valves (>25%, P<0.05). Single cell RNA sequencing of the aortae of benzene-exposed mice revealed 11 major cell types (e.g., vascular smooth muscle cells (VSMCs), endothelial cells, macrophages, T cells, etc.) categorized into 23 sub-populations. snRNAseq and CyTOF analysis showed that benzene exposure robustly increased (P<0.05) CD4
+
and CD8
+
T-cells, and B-cells in the lesions. Clustering of T cells showed significantly higher expression (P<0.05) of CD4, CD8, and Th17 marker RAR Related Orphan Receptor C (RORc). snRNAseq data also suggested increased cell proliferation and >1.5-fold increase in VSMC number following benzene exposure. LC-MS analysis revealed that benzene exposure differentially regulated the abundance of 930 proteins (at least 2 two unique peptides) in innominate plaque. Importantly, several of the proteins involved in an extracellular matrix organization and elastic fibre formation (e.g.
Elastin, Fibronectin
, and
Latent transforming growth factor beta binding protein 1
) were downregulated in benzene-exposed mice. These data agree with the snRNAseq data.
In vitro
, benzene metabolite hydroquinone (HQ, 1 μM) induced ROR-gamma, the transcription factor that regulates Th17, in spleen-derived CD4
+
T cells (P<0.05). HQ (0.1 μM) also increased protein kinase C activity and proliferation of human aortic smooth muscle cells (P<0.001).

Conclusion:
Benzene exposure exacerbates atherosclerosis and compromises plaque cellularity and stability.
Abstract 4147152: First Implantation of Atrial Leadless Pacemaker in Atriopulmonary Fontan
Authors: Wilbur Jameson , Marcus Mason , O'Hara Patrick , Egbonim Emmanuella , Kataruka Akash , Khera Amit , Daniels James
Published: November 2024

Introduction:
Patients with Fontan circulation are at an increased risk of sinus node dysfunction and atrial tachyarrhythmias. These are associated with significant morbidity and mortality, and management constitutes a significant clinical challenge.

Case Description:
A 44-year-old male with right ventricular hypoplasia, tricuspid and pulmonic valve atresia and a ventricular septal defect, corrected with a modified Blalock-Taussig Shunt, bidirectional Glenn Shunt and atrio-pulmonary Fontan, was admitted with a supraventricular tachycardia (SVT) and heart failure. His electrocardiogram showed a narrow complex mid-RP tachycardia consistent with atypical atrial flutter or atrial tachycardia. His echocardiogram showed an LVEF of 21%. He was started on a beta-blocker and loaded with dofetilide, resulting in bradycardia, QT interval prolongation and Torsades de Pointes. Amiodarone was substituted, but he had incessant SVTs. He was taken for an electrophysiology study and radiofrequency ablation of a right-sided re-entrant flutter around an area of block in the anterior septum. Four additional unstable atrial tachycardias were induced but not ablated. He was discharged, then readmitted within hours for SVT. Due to insurance status, the patient was not a candidate for transplant or Fontan revision. To enable treatment with a beta-blocker, an Abbott leadless atrial pacemaker (AVEIR AR) was implanted in the high lateral Fontan, in an area of normal voltage (Figure 1). Post-implant interrogation showed stable device parameters (capture 0.25 V @ 0.4 ms, sensing 7.6 mV, impedance: 380 Ω).

Conclusions:
This is the first case of an AVEIR AR implanted within an atrio-pulmonary Fontan circulation. Access to atriopulmonary Fontan circulation for endovascular device therapy is feasible, but requires careful pre-procedural planning to ensure vascular patency, and anatomic and physiologic feasibility. Leadless pacing mitigates complications from endocardial and epicardial pacing systems, but long-term safety and efficacy are unknown.
Abstract 4147160: Hashimoto Thyroiditis and Congenital Long QT Syndrome: A Dangerous Co-morbidity Causing Torsades
Authors: Acharya Ramesh , Subramany Revathy , Pandit Deepti , Schuller Dan , Tripathi Byomesh
Published: November 2024

Hypothyroidism leads to a prolonged QT interval due to modulation of the potassium channel by low circulating T3, leading to a disproportionate lengthening of the action potential. Patients with Long QT syndromes (LQTS) have an increased risk of symptomatic ventricular arrhythmias and sudden cardiac death (SCD), which can be exacerbated by co-existing hypothyroidism.

Case Description:
A 40-year-old female with a previous history of Congenital LQTS, Type 1 diabetes mellitus, anemia, and untreated hypothyroidism was brought to the hospital by EMS with an abrupt onset of palpitations and disorientation following multiple (>30) AICD shocks, with no identifiable triggers. EMS telemetry monitoring in route to the hospital revealed torsades de pointes, following which she received 4g Magnesium Sulfate IV, and reverted to sinus rhythm. ECG in ICU revealed sinus rhythm with prolonged QTc of 515 ms and elevated troponin. The physical exam was unremarkable.

The patient was started on electrolyte replacements and telemetry monitoring. Additional lab testing revealed high TSH with low T4 as seen in Table 1. Her myxedema coma score was markedly elevated at 40 indicating severe hypothyroidism. Thyroid peroxidase antibody was >600 IU/mL indicating Hashimoto's thyroiditis. ECHO showed LVEF is 55–60% with no wall motion abnormalities. Due to elevated troponin, left-heart catheterization was done which showed normal coronaries. The patient was treated with IV hydrocortisone, IV levothyroxine, oral liothyronine, and propranolol, following which she had no more episodes of Torsades, and QTC improved to her baseline of 479 ms. The patient was discharged home with endocrinology and cardiology follow-up.

Discussion:
Hypothyroidism is associated with prolongation of QTc and the risk of ventricular arrhythmias. Assessment of thyroid function is of high value in QT prolongation syndromes to avoid SCD incidence. Urgent electrolyte replacement and levothyroxine replacement therapy are warranted.
Abstract 4147177: Unveiling the Novel Therapeutic Role of PDE10A-Mediated Functional Protein Complex in Cardiac Hypertrophy
Authors: Chen Si , Fan Xinyue , Xu Sumin , Zhu Nichen , Shi Hangchuan , Yan Chen
Published: November 2024

Heart failure is a leading cause of death in the United States, and is associated with significant myocardial deterioration. cAMP and cGMP play critical roles in cardiovascular biology and disease. cAMP and cGMP form multiple spatially discrete and functionally distinct cyclic nucleotide 'pools,' each associated with unique multi-protein complexes comprising cyclases, PDEs, and other signaling molecules, contributing to distinct biological functions. Phosphodiesterase 10A (PDE10A) is able to hydrolyze both cAMP and cGMP. Our previous published study provides strong evidence supporting a critical role of PDE10A induction in pathological cardiac remodeling and suggest the therapeutic potential of PDE10A inhibition. However, the cellular and molecular mechanisms and the sources of cyclic nucleotides that are regulated by PDE10A remain unknown. Our encouraging results revealed that the anti-hypertrophic effect of PDE10A inhibition/deficiency is dependent on cAMP/PKA signaling in cultured adult mouse cardiomyocytes (CM). We identified the existence of adenosine-dopamine receptor (A
2A
R-D
2
R) heterodimer and the connection of PDE10A with A
2A
R-D
2
R signaling, by which PDE10A inhibition uniquely promotes heterodimerization of A
2A
R-D
2
R, and biased activation of D
2
R/β-arrestin2 (βarr2) through A
2A
R/cAMP/PKA-mediated phosphorylation of D
2
R in CMs. Consistent with what we found in CM, disruption of A
2A
R-D
2
R heterodimer or D
2
R/ βarr2-biased activation significantly abolish the protective effects of PDE10A inhibition on cardiomyopathy and dysfunction
in vivo
. Additionally, we found that activation of D
2
R/βarr2 signaling attenuates stress-induced cardiac remodeling and dysfunction
in vivo
. Together, these results strongly suggest that PDE10A plays a critical role in pathological cardiac remodeling by promoting CM hypertrophy through regulation of A
2A
R-D
2
R/βarr2 biased signaling. Targeting PDE10A and GPCR heterodimerization in CMs may represent a novel therapeutic strategy for treating cardiac diseases.
Abstract 4147186: Impact of Naples Prognostic Score on Clinical Outcomes in ST-Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis.
Authors: Amin Ahmed Mazen , Turkmani Mustafa , Al Barznji Saman , Elbenawi Hossam , Salam Donna
Published: November 2024

Background:
Naples prognostic score (NPS) is a recently developed tool for assessing inflammatory and nutritional status. It is commonly used to evaluate cancer patients.

Purpose:
We aimed to investigate the impact of NPS on clinical outcomes in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI).

Methods:
We comprehensively searched PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through June 2024. We conducted a systematic review and meta-analysis pooling dichotomous data using risk ratio (RR) with a 95% confidence interval (CI). All analyses were performed using R V. 4.3.1.

Results:
We included five studies with a total of 12,785 patients. Comparing high NPS (3-4) to low NPS (0-2), high NPS (3-4) was significantly associated with an increased incidence of overall mortality (RR: 2.21, 95% CI [1.85, 2.65], P < 0.01), shock (RR: 1.85, 95% CI [1.33, 2.57], P < 0.01), acute kidney injury (RR: 1.54, 95% CI [1.15, 2.08], P < 0.01), left ventricular thrombus (RR: 2.93, 95% CI [1.44, 5.94], P < 0.01), and no-reflow (RR: 1.35, 95% CI [1.17, 1.57], P < 0.01). However, there was no significant difference between high NPS (3-4) and low NPS (0-2) regarding in-hospital mortality (RR: 1.82, 95% CI [0.99, 3.37], P = 0.06).

Conclusion:
Our meta-analysis highlights the importance of evaluating inflammation and malnutrition status in STEMI and shows that routine blood tests can provide prognostic insights. NPS can help predict different clinical outcomes in STEMI patients undergoing PPCI. While it does not affect in-hospital mortality, its simplicity and accessibility make it useful for clinical risk assessment and long-term prognosis. Further studies are needed to investigate its predictive value further.