bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4136511: Targeting ATP Citrate Lyase: A Novel Therapeutic Strategy for Vascular Remodeling in Pulmonary Hypertension
Authors: Grobs Yann , Romanet Charlotte , Lemay Sarah-Eve , Bourgeois Alice , Voisine Pierre , Theberge Charlie , Sauvaget Melanie , Breuils Bonnet Sandra , Martineau Sandra , Reem EL-Kabbout , Pelletier Andreanne , Mougin Manon , Dumais Elizabeth , Perron Jean , Flamand Nicolas , Potus Francois , Provencher Steeve , Boucherat Olivier , Bonnet Sebastien
Published: November 2024

Introduction:
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease characterized by a progressive obliteration of distal pulmonary arteries (PA), which is driven by a cancer-like pro-proliferative phenotype of smooth muscle cells (SMCs). A metabolic shift towards glycolysis and changes in the epigenetic landscape contribute to this abnormal phenotype. ATP Citrate Lyase (ACLY) is an enzyme that plays a role in promoting the Warburg effect, lipid synthesis, and chromatin remodeling in cancer. However, its role in PAH remains unknown.

We hypothesized that ACLY is upregulated in PAH and supports the abnormal phenotype of PAH-PASMCs

.

Methods/Results:
To investigate this hypothesis, we measured ACLY expression in human distal pulmonary arteries and isolated PASMCs from PAH patients (immunoblot/Immunofluorescence). We found increased expression and activation of ACLY in PAH-PASMCs, with preferential localization in the nucleus. Inhibition of ACLY using BMS-303141 or siACLY decreased PAH-PASMCs proliferation (Ki67/MCM2, PLK1, PCNA) and survival (Annexin V/SURVIVIN). ACLY inhibition also reduced glycolysis markers and increased mitochondrial respiration. Additionally, the inhibition of ACLY lowered cholesterol levels and lipid droplet accumulation in PAH-PASMCs. Further analysis showed that ACLY promotes nuclear acetyl-CoA production, leading to acetylation of specific histone proteins and GCN5-mediated transcriptional activation of genes involved in cell cycle progression. The transcription factor FOXM1 appeared to mediate this genetic signature.
In vivo
, pharmacological inhibition of ACLY using BMS-303141 significantly improved pulmonary vascular remodeling (Elastica Van Gieson staining, EVG) and right ventricular function (RVSP, mPAP, TAPSE, S-Wave, SV by echocardiography and right heart catheterization) in Su/Hx-challenged rats with established PAH. SMC-specific
Acly
K.O mice were protected against Su/Hx-induced PAH. Consistently, tamoxifen-induced SMC-specific
Acly
deletion improved hemodynamics parameters in Su/Hx mice. These therapeutic effects were associated with a reduced acetylation of H3K27 and H3K9 (IF).
Ex vivo
, inhibition of ACLY attenuated vascular remodeling (EVG) in human precision cut lung slices exposed to a growth factor cocktail.

Conclusion:
Our study reveals that ACLY plays a critical role in vascular remodeling in PAH and its pharmacological inhibition may represent a novel and attractive avenue as therapeutic treatment.
Abstract 4136554: Comparison of short- and long-term atherosclerotic cardiovascular disease risk assessment tools in US young adults
Authors: Zhang Yiyi , Xia Mengying , Reynolds Kristi , Zhou Hui , Zhou Mengnan , Allen Norrina , Gauen Abigail , Petito Lucia , Xanthakis Vanessa , Safford Monika , Colantonio Lisandro , Rana Jamal , Bellows Brandon , Moran Andrew , An Jaejin
Published: November 2024

Background:
In 2023, the AHA published the PREVENT equations for estimating atherosclerotic cardiovascular disease (ASCVD) risk in adults aged 30-79 years.

Research Questions:
In young adults aged 20-39 years, does PREVENT improve risk prediction for 10- and 30-year ASCVD compared with existing risk assessment tools recommended in the current US guidelines (i.e., Pooled Cohort Equations [PCEs] and Pencina et al. equations)?

Aims:
To compare the performance of PREVENT vs. PCEs in predicting 10-year ASCVD, and PREVENT vs. Pencina equations in predicting 30-year ASCVD in young adults.

Methods:
We analyzed data from two complementary sources: (1) pooled data from two large cohorts: Coronary Artery Risk Development in Young Adults (CARDIA) and Framingham Heart Study (FHS; including the Offspring, Third Generation, Omni 1, and Omni 2 cohorts), and (2) electronic health records from Kaiser Permanente Southern California (KPSC). We included adults aged 20-39 years without a history of ASCVD at baseline. The outcome was incident ASCVD (defined as myocardial infarction, fatal coronary heart disease, fatal and nonfatal stroke) at 10 or 30 years. Model discrimination (Harrell’s C) and mean calibration (estimated as the ratio of predicted to observed event rates) were calculated for the overall population and stratified by sex and race/ethnicity.

Results:
We included 7,606 young adults (mean age 29 years, 53% female, 30% Black) from the pooled cohorts, and 284,667 (mean age 32 years, 61% female, 8% Black, 46% Hispanic) from KPSC. When predicting 10-year risk, PREVENT improved discrimination in both the pooled cohort (ΔHarrell’s C=0.052; 95% CI: 0.014, 0.095) and KPSC (ΔHarrell’s C=0.039; 95% CI: 0.028, 0.049) compared with the PCEs. PREVENT had good calibration (mean calibration ranged from 0.77 to 1.54), whereas the PCEs overestimated 10-year risk (mean calibration ranged from 1.99 to 4.82). When predicting 30-year risk, discrimination was similar for PREVENT and Pencina equations, but both algorithms underestimated 30-year risk with PREVENT showing worse calibration (mean calibration 0.61).

Conclusion:
PREVENT improved 10-year ASCVD risk prediction in young adults compared to the PCEs but underestimated 30-year risk.
Abstract 4136604: Efficacy of angiotensin receptor blockers in thoracic aortic aneurysm: meta-analysis of randomized controlled trials
Authors: Tanriverdi Lokman Hekim , Dogan Muhammed Melih , Barrett Annie , Zafar Mohammad , Ziganshin Bulat , Elefteriades John
Published: November 2024

Background:
Thoracic aortic aneurysm (TAA) poses a significant risk of aortic dissection and mortality. Angiotensin receptor blockers (ARBs) have been proposed as a potential therapeutic intervention to mitigate these risks but their effects are uncertain.

Aim:
To evaluate the efficacy of ARBs in patients with TAA.

Methods:
A comprehensive search of Cochrane CENTRAL, Ovid Medline R, Pubmed, and Web of Science yielded 2563 records, from which 8 unique randomized controlled trials (RCTs) (including 7 Marfan and 1 bicuspid aortic valve+TAA populations) comprising 1575 patients were included in the analysis. The primary outcome measures were aortic dissection and all-cause mortality. Pooled risk ratios (RR) or mean differences (MD) in an inverse variance random-effects model were generated and analyses were performed with “meta” package in R (version 4.3.2).

Results:
Our analysis reveals no significant beneficial effect of ARBs on aortic dissection (RR 0,62 [95%CI, 0,20; 1,92], I
2
:0%) and all-cause mortality (RR 0,61 [95%CI, 0,18; 2,05], I
2
:0%), irrespective of specific ARB agents (including losartan, irbesartan, and telmisartan), comparators (beta blocker, placebo, or no treatment), disease condition (Marfan syndrome or bicuspid aortic valve), and patient demographics (children or adults). Additionally, there were no significant differences observed between ARB and control groups in changes in ascending aorta and aortic annulus diameter, as well as aortic Z-score at the 3-year mark, including the annual change in ascending aorta (MD 0.04 mm/year [95% CI, -0.07 to 0.15], I
2
:0%) and aortic root diameter (MD -0.06 mm/year [95% CI, -0.22 to 0.10], I
2
:81%) by echocardiography. However, there was a significant reduction in aortic root diameter as assessed by MRI (MD -0.48 mm/year [95%CI, -0.89 to -0.08]) and echocardiography (MD -0.51 mm/3year [95%CI, -0.85 to -0.17]), with low heterogeneity when compared with control. Risk of aortic surgery and severe adverse events were also comparable.

Conclusion:
We found no significant beneficial effect of ARBs in reducing the risk of aortic dissection or all-cause mortality in patients with TAA. Despite observing a significant reduction in the aortic root diameter by MRI and echocardiography with ARB therapy, other imaging outcomes were comparable between ARB and control groups.
Abstract 4136621: Efficacy of Empagliflozin in Heart Failure with Preserved Ejection Fraction is related to the presence of echocardiographic features of diastolic dysfunction in the EMPEROR-Preserved trial.
Authors: Coats Andrew , Butler Javed , Zimmet Hendrik , Anker Stefan
Published: November 2024

Introduction:
Efficacy of SGLT2i empagliflozin in Heart Failure is seen across the LVEF spectrum and in multiple clinical subgroups, with diverse mechanisms of action. We hypothesized that objective echo evidence of diastolic dysfunction (DD) in HFpEF may predict the response to empagliflozin.

Methods:
We defined DD as the presence of LAVI ≥34 mL/m
2
, E/e ≥13 or LVMi >115 (males) or >95 (females) and created three categories with 0, 1 or ≥2 DD criteria. We report the impact of baseline DD on response to empagliflozin therapy and adverse effects.

Analyses were performed using the intention-to-treat principle. For time-to-first-event analyses, differences in treatment effects across the three DD categories were assessed by a Cox proportional hazards model, with pre-specified covariates of age, gender, region, diabetes, LVEF, and eGFR. Total events were assessed using a joint frailty model, with CV death (CVD) as a competing risk.

Results:
Of 5988 patients in EMPEROR-Preserved 3766 (63%) had no baseline DD, 1619 (27%) one and 603 (10%) ≥2 measures. The percentage of males decreased as DD category increased, 57.2% for none, 54.2% for one and 46.6% for ≥2, p <0.0001. Other demographic features significantly associated with DD categories were race, ethnicity and region and it was more common with age, with lower HR, DBP, body weight and eGFR. DD was more frequent with ischaemic aetiology and higher LVEF, but not with baseline NT−proBNP, DM or COPD. Time to HHF or CVD showed a progressive treatment effect across the three DD categories (interaction p-value 0.0014), with estimated HR’s of 0.91 (none present), 0.64 (1 present) and 0.49 (>=2). A significant treatment-by-subgroup interaction was also observed for the total number of HHF, with estimated HR’s of 0.95 (none present), 0.52 (1 present) and 0.29 (≥2).

In the responder analysis, ≥10 point improvement in KCCQ at week 52 showed a treatment induced change that was consistent across DD categories (interaction p-value 0.92). The safety profile was consistent across DD classes.

Conclusions:
Baseline echocardiographic DD predicted an improved clinical response to Empagliflozin in a graded fashion, suggesting the mode of action may target specific changes in diastolic performance.
Abstract 4136698: Comparative Analysis of Transthoracic and Transesophageal Echocardiography for Diagnosis of High-Risk Patent Foramen Ovale
Authors: Jo Ha Hye , Kim Ga Yun , Song Jae-kwan
Published: November 2024

Background:
Transthoracic contrast echocardiography using hand-agitated saline and provocative maneuver (cTTE) has been considered a gold standard of diagnosis of patent foramen ovale (PFO), and transesophageal echocardiography (TEE) is generally recommended for selected patients who are going to undergo percutaneous closure of PFO. Recent studies have highlighted the clinical significance and prognostic implication of various anatomical features of PFO and the adjacent atrial septum, and risk stratification using the concept of ‘a high-risk PFO (HRPFO)’ has been widely accepted. We sought to evaluate the diagnostic role of TEE with contrast study (cTEE).

Methods:
Clinical data from patients who underwent both cTTE and cTEE without sedation for evaluation of cryptogenic stroke was retrospectively analyzed. The bubble gradings of right-to-left shunt were classified into four groups: grade 0 (none), grade 1 (< 20), grade 2 (20-99 bubbles), and grade 3 (≧100 bubbles). HRPFO was defined as PFO with an atrial septal aneurysm or hypermobile atrial septum, or PFO with large amount of shunt (≧20 bubbles), or PFO size (distance between septum secundum and primum) of ≧2 mm.

Results:
From January 2017 to December 2022, a total of 572 patients underwent both cTTE and cTEE. The prevalence of PFO was 65.9 % (377 patients), and 331 patients (57.9% of the total, 87.8% of those with PFOs) were diagnosed with HRPFO using cTTE or cTEE. The prevalence of grade 2 and 3 was significantly higher in cTEE than in cTTE among proven PFO cases (68.7 % vs 75.6 %, P = 0.04). Among patients initially assessed as having a low-risk PFO or no PFO by cTTE, 22% were subsequently reclassified as having a HRPFO following cTEE. As a result, the positivity of HRPFO significantly increased from 46% to 56.8% after cTEE (P < 0.001). The sensitivity of cTTE for diagnosing a HRPFO was significantly lower than that of cTEE (79.5 % vs 98.2 %, P < 0.001).

Conclusions:
Diagnostic performance of cTTE can be significantly improved with the addition of cTEE without sedation. Given the beneficial effects of percutaneous closure of HRPFO, cTEE without sedation should be considered a useful screening test for patients with cryptogenic stroke.
Abstract 4136724: Early Adoption of Sodium-Glucose Cotransporter-2 Inhibitor Among Patients Hospitalized with Heart Failure and Preserved Ejection Fraction in the United States
Authors: Abdel Jawad Mohammad , Spertus John , Greene Stephen , Ikeaba Uchechukwu , Chiswell Karen , Fonarow Gregg , Chan Paul
Published: November 2024

Introduction:
In August 2021, the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved) found that empagliflozin reduced rates of cardiovascular death and hospitalization by 21% in patients with heart failure with mildly reduced ejection fraction of 41-49% (HFmrEF) and with preserved ejection fraction of
>
50% (HFpEF). National trends in Sodium-Glucose Cotransporter-2 Inhibitors
(
SGLT2i) use among patients with HFmrEF and HFpEF following this trial are unknown.

Methods:
We identified patients hospitalized for HFmrEF and HFpEF in the AHA Get With The Guidelines-Heart Failure registry between July 2021 and September 2023. We examined temporal trends in SGLT2i prescriptions at discharge after the publication of the EMPEROR-Preserved trial using the Cochran-Armitage trend test.

Results:
Among 158,849 hospitalizations with an EF > 40% across 557 hospitals, 27,712 (17.4%) had HFmrEF, and 131,137 (82.6%) had HFpEF. Overall, 22,126 (13.9%) patients were discharged with a prescription for SGLT2i, with higher rates among those with HFmrEF (18.5% vs. 13.0% in those with HFpEF). Patients prescribed SGLT2i were more likely to be younger, male, of Black race, have type II diabetes, have Medicaid insurance, and be discharged from large hospitals. After publication of the EMPEROR-Preserved trial during Q3 2021, rates of SGLT2i prescription at hospital discharge increased from 4.2% in Q3 2021 to 23.5% in Q3 2023, with a 29% relative increase in the rate of SGLT2i prescription for each quarter (adjusted OR, 1.29 [95% CI: 1.28, 1.29]; P<.001). Prescription rates increased from 6.1% in Q3 2021 to 31.6% in Q3 2023 among patients with HFmrEF and from 3.8% to 21.9% for patients with HFpEF (Figure).

Conclusion:
In the U.S., the use of SGLT2i at discharge has increased for patients hospitalized with HFmrEF and HFpEF following the publication of the EMPEROR-Preserved trial. However, the majority of eligible patients hospitalized for decompensated HF remain untreated with SGLT2i, indicating the need for further efforts to apply the scientific findings into clinical practice.
Abstract 4136812: Optimal Pacing for Cerebral Perfusion: Elucidating Relationship Between Resting Pacemaker Heart Rate and Pulse Pressure
Authors: Moustafa Ahmed , Mian Muhtashim , Khan Habib
Published: November 2024

Background:
Cognitive decline and dementia are significant global health concerns, with hypertension being a major risk factor. Increasingly, the elderly population is receiving pacemakers, and the pacing rates are set as low as 50bpm. Moreover, the relationship between blood pressure (BP) components, particularly diastolic BP (DBP) and pulse pressure (PP), and the risk of cognitive decline or dementia remains complex. The highest risk is observed in patients with low DBP and concurrently increased PP, likely indicating vascular stiffness. To our knowledge, no studies have assessed the programming of pacemakers to increase heart rates to target DBP and PP improving cerebral perfusion.

Objectives:
In patients with permanent pacemakers, resting heart rate (HR) can be artificially increased, and its consequence on hemodynamics, including PP, can be easily measured. This study aims to investigate the impact of increasing resting HR on PP in patients with poor vascular compliance. Secondary outcomes include evaluating changes in DBP, SBP, and cardiac output, as well as assessing patient tolerance to higher-paced heart rates through recording subjective symptoms.

Methods:
The study will employ a prospective cross-sectional interventional design. Digital plethysmography will be utilized to measure hemodynamic parameters, including systolic blood pressure (SBP), DBP, PP, and cardiac output, at baseline resting-paced heart rates. Subsequently, the pacemaker resting heart rate will be incrementally increased to a final rate of 100 beats per minute (bpm), with measurements taken 2-5 minutes after each change.

Results:
Ten out of twenty patients were recruited, with a mean age of 75.3 years old. The median change in PP from baseline HR of 70 to 100 was -8.7% (IQR -18.8 - +2.8, p= 0.114), SBP 4.2% (IQR 0 – 11.9, p=0.059), and DBP 20.1% (IQR 12.9 -23, p=0.005). There were no adverse outcomes and no patient-reported symptoms during higher pacing rates.

Conclusion:
This study provides the basis for proof of concept. Since an increased HR decreases PP, this will be subsequently tested against improvement in cerebral perfusion by cerebral Doppler studies, and its impact on cognitive function will be tested. This has the potential to change the standard of practice for patients with pacemakers and allow for collaboration across multiple specialties such as neurology, geriatric medicine and cardiology.
Abstract 4136819: Necrotizing Enterocolitis is More Common After Hybrid Stage 1 Palliation Than Norwood Without Clear Risk Factors
Authors: Pierick Alyson , Liken Hillary , Zampi Jeffrey , Romano Jennifer , Strohacker Courtney , Duimstra Ashley , Lowery Ray , Yu Sunkyung , Sower Christopher
Published: November 2024

Background:
Infants with congenital heart disease are at high risk of developing necrotizing enterocolitis (NEC), with increased morbidity and mortality compared to infants without heart disease who develop NEC. Shunted single ventricle patients are at even higher risk. The hybrid stage 1 palliation (HS1P) is an alternative to the Norwood procedure for high-risk single ventricle patients or as initial palliation for patients with future two ventricle repair, as bridge to transplant, or as destination therapy. Few small studies have shown similar or slightly higher rates of NEC after HS1P compared to after Norwood.

Aims:
To evaluate the incidence, risk factors, and outcomes of NEC in HS1P versus Norwood patients.

Methods:
This is a single-center retrospective cohort study of all neonates who underwent HS1P or Norwood procedure from 2011-2022. Demographic data and episodes of NEC (defined using modified Bell’s criteria) were collected. NEC incidences and risk factors were compared between HS1P and Norwood patients using Chi-square test. For HS1P patients, more extensive data were collected including planned and final physiologic outcomes (single ventricle palliation, biventricular repair, transplant, and destination) and primary patient risk factors that led to HS1P. Risk factors and clinical outcomes of HS1P patients with and without NEC were compared using standard univariate tests.

Results:
The cumulative incidence of NEC in the HS1P group was 53% versus 37% in the Norwood group (p=0.01) and HS1P patients had more NEC episodes than the Norwood group (median 2 vs 1, p=0.03). Suspected NEC (stage 1A/1B) accounted for 70-75% of NEC cases in both groups. Only two infants, both in the HS1P group, had surgical (stage 3B) NEC. We found no differences in baseline demographics between patients with and without NEC in both HS1P and Norwood groups. In the HS1P group, NEC was associated with longer hospital length of stay (LOS), (median 49 days vs 23 days, p<0.0001) and greater need for tube feeds at 1 year (32% of the NEC group exclusively orally fed versus 43% of the non-NEC group, p=0.03). Final physiologic outcome was not associated with development of NEC in the HS1P group (p=0.38).

Conclusions:
While the exact risk factors or predictors are not clear, NEC is more common after HS1P compared to Norwoods and is associated with longer hospital LOS and late feeding difficulty. Further studies to better understand the physiologic causes of NEC in the HS1P population are needed.
Abstract 4136822: Implementation of a Community-Engaged Amputation Prevention Intervention in Rural Appalachia
Authors: Minc Samantha , Wright Lauren , O'Dell Jordyn , Beimel Christiana , Rothenberg Paul , Hopkins Rosalie , Smith Gordon , Armstrong David , Misra Ranjita , Peek Monica , ZimmermanOwen Pamela , Dino Geri
Published: November 2024

Amputation is a devastating complication of diabetes and peripheral artery disease and a marker for health inequity. Implementation Science (IS) and Community Engaged-Research (CenR) allow for real-world adaptation of evidence-based interventions and provide critical frameworks for reproducibility and sustainability. However, few amputation interventions use these approaches. We describe the feasibility and acceptability of an IS and CEnR driven amputation intervention in a high-risk rural community.

A Pre-Post mixed methods design was used (Fig 1). Intervention components were mapped to the Social-Ecological Model (Fig 2) and guided by the CFIR. Community and Project Advisory Boards collaborated on needs assessment, mobilizing resources, intervention adaptation, data review and dissemination. A 3-component intervention was implemented in 2 clinics to improve local foot care. Components included diabetic foot exams (DFEs), a multidisciplinary limb preservation team, and a “hot-foot” hotline. Pre-implementation, a retrospective chart review was performed along with focus groups. DFE training was then conducted at each site. After training, a prospective chart review was performed with clinic check-ins for 12 months. Focus groups were held 6- and 12-months post-implementation. Concurrently, monthly multidisciplinary teleconferences were held, and a “hot-foot” phoneline connected providers to specialty nurses.

At baseline, 155/224 (69.2%) patients received an annual DFE, 17% had all four exam components, 15.6% had foot abnormalities identified and 3.6% were referred to specialists. At 12-months 212/268 (79.1%) patients received a DFE, 84.7% had all components, 54.9% had abnormalities and 20.1% were referred. All findings were statistically significant. Clinically there was a significant decrease in patients with foot wounds, infection, and foot-related hospitalization/ED visits. There were no changes in amputations. (Table 1) The virtual teleconference completed 12 sessions. The hotline was used once with clinicians reporting they did not need it.

We demonstrate successful, sustained implementation of an amputation prevention intervention in a high-risk rural community using IS and CEnR. This approach was crucial for overcoming barriers to intervention implementation in a resource poor environment. Additional research to assess patient experience, understand key components of the intervention and study scalability and clinical effectiveness is planned.
Abstract 4136863: Diffuse Functional and Structural Abnormalities in Fibrosis: Potential Structural Basis for Sustaining Atrial Fibrillation
Authors: Kwan Eugene , ghafoori elyar , Good Wilson , Regouski Misha , Moon Boyce , Fish Jeffrey , Hsu Edward , Polejaeva Irina , MacLeod Rob , Dosdall Derek , Ranjan Ravi
Published: November 2024

Background:
Structural remodeling is associated with atrial fibrillation (AF), but detailed structural and functional characteristics is not well defined.

Goal:
Using a novel transgenic goat model with cardiac-specific overexpression of TGF-β1 leading to increased cardiac fibrosis, we evaluated detailed structural and functional differences between fibrotic and healthy regions of the atria.

Methods:
Ex-vivo MRI and histology were used to evaluate fibrosis, fiber disarray, and structural anisotropy. Ex-vivo MRI intensity values were scaled to standard deviations around the mean. The functional analysis examined conduction speeds and direction heterogeneity. Conduction anisotropy was measured along the fiber direction obtained with diffusion tensor imaging.

Results:
The transgenic goats (n=12) had, on average, 21% of the left atria labeled as fibrotic determined from ex-vivo MRI. The histology samples taken from the labeled fibrotic regions had an increase in fibrosis percentage compared to labeled healthy regions (7.78±3.76% vs 2.80±1.86%, p<0.01). The structural anisotropy was lower in fibrotic regions (0.196±0.002 vs 0.244±0.002, p<0.01). Fiber disarray was greater in the fibrotic regions (20.3±0.2° vs 19.2±0.1°, p<0.01). The fibrotic regions had slower conduction speeds (0.78±0.02 m/s vs 1.12±0.02 m/s, p<0.01) and more aligned conduction directions (30.5±0.2° vs 31.6±0.1°, p<0.01), potentially developing unidirectional conduction block. Conduction anisotropy, measured on the fiber directions, was found to be lower in the fibrotic regions (1.86±0.05 vs 2.10±0.02, p=0.04). As scaled MRI intensity increased, the conduction speed, heterogeneity, and anisotropy all decreased.

Conclusions:
Functional and structural differences exist between fibrotic and healthy regions of the atria. Though statistically significant, the changes are not discrete. The correlation showed gradual functional abnormalities with MRI intensities. Fibrotic regions tended to have increased fiber disarray, slower conduction, and more unidirectional propagation with lower conduction and structural anisotropy. Diffuse functional and structural abnormalities may allow fibrotic regions to serve as a substrate to sustain AF.
Abstract 4136869: Time Course and Predictors of PVC Recurrence After Acutely Successful Catheter Ablation
Authors: Cimmino Michael , Dikdan Sean , Kloo Juergen , Basil Anuj , gangireddy chethan , Laslett David , Smietana Jeffrey , Whitman Isaac , Cooper Joshua , Cronin Edmond
Published: November 2024

Introduction:
In prior studies, predictors of long-term success following acutely successful radiofrequency (RF) ablation have included female-sex, single-PVC morphology and EGM-QRS > 24ms. Time course and predictors of PVC recurrence following acutely successful ablation has been less well documented. Use of extended ambulatory monitoring in the immediate post-procedural period can help to identify those with early recurrence.

Goals:
To define time to recurrence and predictors of recurrence of PVCs after RF ablation following acutely successful ablation.

Methods:
Consecutive patients from January 1
st
, 2016 through December 31
st
, 2023 undergoing PVC ablation with available post-ablation extended ambulatory monitoring (Zio, iRhythm, San Francisco, CA) were retrospectively analyzed. Recurrence was defined as an increase in PVC burden to >5% during monitoring after acute success or failure to have sustained reduction in PVC burden of >80%. Acute success was defined as elimination of the targeted PVC after the last ablation lesion. Long-term succes was defined as absence of targeted PVC's during all follow-up visits and PVC-burden < 5% on follow-up monitoring.

Results:
Among 121 patients who underwent successful PVC ablation, 101 (83.4%) had long-term success and 20 (17%) had recurrence. Patients with recurrence were older (62.4 ± 12 vs 55 ± 13., p = 0.019), had a higher incidence of CAD (13 (13%) vs 9 (45%), p = 0.001) and CHF (40 (40%) vs 15 (75%), p = 0.004). At time of ablation, the recurrence group was also more likely to have >1 PVC morphology (6 (6%) vs 8 (40%), p = <0.001). Location and earliest activation time of the predominant PVC were not assocated with likelihood of recurrence. Within the recurrence group, 13 (65%) had recurrence in the immediate 2 week post-procedural period with an average time to recurrence of 3.9 days.

Conclusion:
Recurrence occured in slightly less than 20% of cases with a relatively high proportion of those occuring within the immediate 2 week post-procedural period during extended ambulatory monitoring. The presence of greater than 1 PVC morphology at time of ablation is a risk factor for recurrence suggesting a higher likelihood of acute suppression without durable resolution in those instances.
Abstract 4136873: The Role of Socioeconomic Status in the Association Between Cardiovascular Polygenic Risk Score and Cardiovascular Events
Authors: Bhaskar Saigeetha , Pirruccello James , Hoffmann Thomas , Beatty Alexis
Published: November 2024

Introduction:
Polygenic risk scores (PRS) provide a summation of small-effect genetic variants that predict cardiovascular (CV) disease risk. Socioeconomic status (SES) can also impact CV risk, but it is unknown whether SES modifies the effects of PRS on CV events.

Hypothesis:
The association between CV PRS and CV events is modified by SES.

Methods:
Participants without CV disease at baseline from the UK Biobank prospective cohort study were followed from recruitment (2006-2010) through 2023. We included participants with genetic data (for CV PRS) and CV risk factors assessed at baseline (hemoglobin A1c, total cholesterol, blood pressure, body mass index, physical activity, tobacco use, and sleep). The CV PRS was centered at zero and standardized to one unit variance within each ancestry group. SES was defined by tertiles of index of multiple deprivation (from housing, crime, income, education, employment, health deprivation and disability, and neighborhood environment). The primary outcome was CV events (myocardial infarction, heart failure hospitalization, stroke, or death). Using Cox proportional hazard models, we estimated the total effect of PRS on CV events, tested for interaction of SES in the association between PRS and CV events, and estimated the direct effect of PRS on CV events by adjusting for age, sex, CV risk factors, and SES.

Results:
There were 201,374 participants (mean age 55.9 (± 8.1), 53.4% female). CV events occurred in 21,916 (10.9%) participants: 5,754 (2.9 %) myocardial infarctions, 4,061 (2.0%) strokes, 4,312 (2.1%) heart failure hospitalizations, and 12,782 (6.4%) deaths. Each unit of PRS was associated with 1.17 times the risk of CV events (HR 1.17, 95%CI 1.15 to 1.18, p-value < .001, adjusted for age and sex). People with the lowest SES had 1.22 times the risk of CV events (HR 1.22; 95%CI 1.18 to 1.26; p-value <.001) and the middle SES had 1.07 times the risk of CV events (HR 1.07; 95%CI 1.03 to 1.10; p-value <.001) compared to the highest SES, adjusted for age, sex, and CV risk factors. PRS remained associated with CV events (HR 1.15, 95%CI 1.13 to 1.16, p-value<.001) after adjusting for age, sex, CV risk factors, and SES. There was no significant multiplicative interaction between SES and PRS for CV events (interaction p-value = 0.45).

Conclusions:
SES is associated with CV events but does not modify the effect of PRS on CV events. Genetic risk remains independently important in CV event risk beyond traditional CV risk factors and SES.
Abstract 4136884: Incidence and Characteristics of Peri-Procedural Complications of Cardiac Implantable Electrical Devices in Breast Cancer Survivors
Authors: Keller Eleanor , Noteware Laura , Accordino Melissa , Connolly Eileen , Saluja Deepak , Goldberg Anne , Wan Elaine , Sayer Gabriel , Biviano Angelo , Uriel Nir , Yarmohammadi Hirad , Raikhelkar Jayant
Published: November 2024

Introduction:
Breast cancer (BC) is the most common non-cutaneous cancer in women. Several BC treatments increase the risk of conduction abnormalities and heart failure, potentially requiring cardiac implantable electrical devices (CIEDs). Due to vascular access devices, surgical management, and chest wall radiation, these patients are subject to upper extremity vascular alterations. There is limited data regarding CIED use in this population.

Research question:
Do patients with BC and CIEDs have different procedural approaches or complications compared to the general population?

Aims:
This study aimed to evaluate CIED placement and periprocedural complications in patients with a history of BC.

Methods:
This was a retrospective study of CIEDs placed at our institution between 2005 and 2023. Patients with a diagnosis of BC prior to time of placement were included. Complications included those within 30 days of the procedure.

Results:
We analyzed 109 female patients (median age of 73 years, IQR 66-80) who received pacemaker (PPM, 58.7%), cardiac resynchronization therapy defibrillator (CRT-D, 22%), implantable cardioverter defibrillator (ICD, 16.5%), or cardiac resynchronization therapy pacemaker (CRT-P, 2.8%). The median time from cancer diagnosis to device placement was 13 years (IQR 7-21). Oncologic therapies are included in Figure 1. In patients with unilateral cancer, most devices (78.4%) were placed contralaterally, with 32% of all devices being right sided. Anatomy related to chemotherapy port altered intraoperative approach in 2 cases and bilateral lymph node dissection necessitated subcutaneous ICD in 1 case. Complications were noted in 12 patients (11%) and included hematoma, lead revision, upper extremity DVT, pericardial effusion, stress cardiomyopathy, perforation, site infection, and worsening of chronic lymphedema.

Conclusions:
BC survivors undergoing CIED placement appear to be at higher risk of periprocedural complications when compared to the general population. They are more likely to undergo right sided device placement to avoid vascular access ipsilateral to prior surgery or radiation. Further studies are required to understand the long-term outcomes of CIED placement in this cohort of patients.
Abstract 4136889: Impact of hypercholesterolemia definitions on prevalence and prognosis of patients without standard modifiable cardiovascular risk factors and ST-segment elevation myocardial infarction.
Authors: Zeller Marianne , Danchin Nicolas , Rousseau Alexandra , Cottin Yves , Sauze Dorian , Goube Pascal , CAYLA Guillaume , PRIEUR Cyril , Auffret Vincent , Simon Tabassome , Steg Philippe
Published: November 2024

Background:
In patients with acute myocardial infarction (AMI), recent studies have intriguingly reported that up to a quarter of AMI patients have none of the 4 main standard modifiable cardiovascular (CV) risk factors (SMuRFs) (i.e. hypertension (HTN), diabetes mellitus (DM), hypercholesterolemia (HC), and smoking) and have worse mortality.

Hypothesis:
We tested the hypothesis that the prevalence and prognosis of SMuRF-less patients varies with the definition of risk factors.

Aim:
Using a French nationwide MI cohort, we aimed to compare SMuRF-less ST-segment elevation MI (STEMI) patients according to 2 HC definitions, given the possibility of using several HC criteria.

Methods:
The French Cohort of Myocardial Infarction Evaluation (FRENCHIE) is a large ongoing AMI cohort, collecting data from all patients hospitalized for AMI < 48 h of symptom onset in 21 French centers. STEMI patients without prior CAD admitted in 2019 to 2022 were studied. DM was defined as prior DM diagnosis, HbA1c>7% or anti-diabetic medications, ongoing or at discharge, HTN was defined as treated or previous HTN diagnosis and smoking was defined as current smoking within the past month. Restrictive HC (RHC) was defined as either a previous diagnosis of HC or statin therapy. Permissive HC (PHC) was defined as previous diagnosis of HC or lipid-lowering therapy, or LDL-C > 135 mg/dL or total Cholesterol > 213 mg/dL.

Results:
Among 8008 patients (mean age 61.5± 12.9y, 22.6% women), 41.4% were smokers, 17.4% had diabetes, and 38.5% HTN. According to HC definitions, the prevalence of HC almost doubled, ranging from 30.3% for RHC to 61.0% for PHC. Consequently, the prevalence of SMuRF-less was divided by ≈ two (21.1% vs 11.3%, respectively), depending on the definition of HC used. Age and sex-adjusted logistic regression analysis showed that PHC, but not RHC, was associated with lower odds of in-hospital death (
figure
). Moreover, having multiple SMuRFs was associated with higher risk of mortality than no SMuRF when using RHC, but not with PHC definition.

Conclusion:
The prevalence and impact on acute mortality of being SMURFless varies largely with the definition of HC. More research is needed, using HC standardized definitions to explore these patients.

Frenchie:
was supported in part by the RHU iVASC grant ANR-16-RHUS-00010 from the French National Research Agency (ANR) as part of the Investissements d’Avenir program. The FRENCHIE cohort is registered with ClinicalTrials.gov, NCT04050956.
Abstract 4137058: Clinical Characteristics and Outcomes of South Asians Presenting with Acute Coronary Syndrome
Authors: Patel Humail , Bulsara Kishen , Srivastava Shreya , Hussain Fahad , Dulmovits Eric , Salam Shafkat , Chandi Mohit , jauhar rajiv
Published: November 2024

Background:
Patients of South Asian descent have a higher incidence of atherosclerotic cardiovascular disease and are affected by clinically significant coronary artery disease at an earlier age when compared to the general population. As a result, they have been shown to have a higher rate of cardiovascular events. This at-risk population has not been well studied as it pertains to acute coronary syndrome.

Methods:
Out of 1610 patients who presented to one of two tertiary care centers between 2021-2022 with a diagnosis of acute coronary syndrome and underwent coronary angiography, 240 patients were identified as being South Asian and were included in the study. 480 non-South Asian patients were randomly selected as controls. A retrospective analysis was conducted to study the demographics, risk factors, clinical presentation, diagnostic features, and outcomes of the two groups.

Results:
South Asian patients who were diagnosed with acute coronary syndrome and underwent coronary angiography were significantly younger than non-South Asian patients (61 vs 65 years, p < 0.001). Though they were less likely to be smokers, they were significantly more likely to have other known risk factors including hypertension, dyslipidemia, and a history of prior myocardial infarction (p < 0.001). South Asians had mean lower HDL (p = 0.02), higher triglycerides (0.006), and higher Hgb A1C (p < 0.001). Surprisingly, rates of multivessel disease (defined as stenosis of 50% or greater in two or three vessels) were similar between the two groups. South Asians were more likely to be referred for CABG after initial coronary angiography most likely due to diffuse disease (p = 0.014). Clinical outcomes including pre-discharge LVEF, and 2-year mortality were similar between the groups.

Conclusions:
South Asians are a notoriously high-risk group when it comes to early-onset and more severe coronary artery disease. The pathophysiology behind this disproportionate manifestation of cardiovascular disease is not entirely understood, but several efforts to delineate this are ongoing. Our data demonstrate that this is at least in part, due to a higher prevalence of conventional modifiable and nonmodifiable risk factors in South Asian patients.
Abstract 4137103: Myofibril Mechanics and Transcriptomic Profiling Confirm Distinct Phenotype of
TNNI3-
Cardiomyopathy Mouse Model
Authors: Silver Elizabeth , Gunes Betul , Fenwick Axel , Cammarato Anthony , Adler Eric , Bushway Paul
Published: November 2024

Introduction:
Cardiac troponin I (cTnI,
TNNI3
gene) is a highly conserved subunit of the sarcomere that inhibits contraction by preventing actin-myosin interaction. Pathogenic
TNNI3
variants can cause both hypertrophic and restrictive cardiomyopathies but lack targeted therapies. We identified a family with restrictive cardiomyopathy carrying a cTnI variant at amino acid 157 (A157V). Using CRISPR-Cas9, we generated a knock-in mouse model reflecting this mutation (A158V in mouse). Our previous studies showed that homozygous A158V mice had impaired cardiac relaxation on invasive hemodynamics but normal lifespan, no echocardiographic changes, and no fibrosis.

Hypothesis:
Myofibril mechanics and transcriptomic studies will better discriminate
TNNI3
A158V mice from WT than previous phenotyping studies.

Methods:
Heart tissue was obtained from wild-type (WT) and homozygous A158V mice at 9-10 months. Myofibrils were isolated from heart tissues and mechanical measurements were completed using the fast solution switching method. RNA was extracted for bulk RNA sequencing.

Results:
Isolated myofibril studies showed significant prolongation of the linear relaxation phase in A158V mice versus controls (p=0.02) but no significant differences in active tension. Unsupervised clustering of bulk RNA samples separated A158V samples from controls, with 44% transcriptional variation derived from genotype. Cardiac changes in the A158V model were confirmed by significant depletion of pathways involved in structural components of the contractile apparatus, including contractile fiber, sarcomere, and I-Band. On an individual gene level, A158V mutated mice displayed higher expression of cardiac remodeling genes such as
Timp1
,
Postn
, and
Tnc
.

Conclusion:
The
TNNI3
A158V variant consistently produces impaired relaxation with myofibril studies showing prolonged linear relaxation phase. Transcriptomic studies highlight distinct clustering of
TNNI3
A158V mice from WT, with prominent depletion in contractile apparatus pathways. Our findings suggest traditional methods to characterize mouse models may fail to capture disease phenotype in cardiomyopathies; however, myofibril studies and transcriptomic profiling may reveal earlier phenotypic changes.
Abstract 4137145: Aortic Stenosis in Pregnancy: A Multidisciplinary Team Approach
Authors: Caplan Alex , Jackson Jordan , kalot Mohamad , Yost Gregory
Published: November 2024

Introduction:
The hemodynamic adaptations that occur during pregnancy can have significant effects on patients with aortic stenosis (AS). These changes can lead to structural changes identified on echocardiogram even during uncomplicated pregnancies. While some cases can be managed with medical therapy and activity modification, others may require valve intervention in the gestational period.

Case:
A 29-year-old female with history of congenital bicuspid aortic valve, G1P0 presented at 42+2 weeks of pregnancy and was admitted to cardiac intensive care unit for continuous hemodynamic monitoring via use of arterial line. Her prior aortic valve disease was treated by valve repair with valvotomy, removal of tissue from pseudo raphe, removal of calcified scar tissue from both commissures, and a mitral valve repair for closure of an iatrogenic tear in her anterior leaflet. She followed closely with maternal fetal medicine and cardiology but became symptomatic at week 28 with lightheadedness, shortness of breath and decreased exercise tolerance (NYHA Class II). By week 33 she noticed lower extremity edema. Despite recommendations for planned delivery, she opted to wait until full term for delivery. Surveillance echoes revealed rising velocities yet stable valve area by planimetry. She ultimately underwent an uncomplicated Cesarean delivery of baby boy in week 42. At 6 months post partum she had successful transcatheter aortic valve replacement.

Discussion:
As the severity of valvular disease worsens there is a higher risk of complications during pregnancy. In our case, aortic valve velocities were elevated due to the expected hemodynamic changes of pregnancy. Thus, echocardiography monitoring should be used to assess the left ventricle’s ability to tolerate and compensate for these changes, while intervening based on symptoms and NYHA classification. We highlight the importance of multidisciplinary collaboration for safe and successful delivery in patients with AS.
Abstract 4137155: Relationship between Subclinical Myocardial Injury and Global Cognitive Performance: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Tomar Shubham , Lidani Karita , Moraes Aline , Huang Shi , Nasir Khurram , Blaha Michael , Heckbert Susan , Hughes Timothy , deFilippi Christopher , Sandoval Yader , Jaffe Allan , DeFilippis Andrew
Published: November 2024

Background:
With demographic trends transitioning towards older adults, dementia and cognitive impairment are predicted to increase dramatically. We aim to elucidate the relationship between subclinical myocardial injury, as indicated by asymptomatic increased levels of high-sensitivity cardiac Troponin (hs-cTnT), and cognitive performance.

Methods:
We studied MESA participants from Exam 1 (2000-02) to Exam 6 (2016-18), categorizing them based on baseline hs-cTnT at Exam 1. Cognitive decline was defined as a decrease of ≥5 units in CASI between Exam 5&6. We used Pearson correlation and linear regression to analyze the association of hs-cTnT levels with CASI scores, and logistic regression to examine the association with cognitive decline. We also explored the relationship between different hs-cTnT categories and cognitive measures. Models were adjusted for demographics, lifestyle, APOE status, comorbidities, and medication use (
Figure
).

Results:
4445 participants had both baseline hs-cTnT and valid Exam 5 CASI scores while only 1776 participants had valid Exam 6 CASI scores. Cohort was predominantly female (53%), mean age of 60 years, and 27% had at least one APOE e4 allele. Median hs-cTnT was 6.32 ng/L, and median CASI scores were 89 at Exam 5 and 91.5 at Exam 6. We found a negative correlation between the log-hs-cTnT at Exam 1 and Exam 5 with CASI scores at Exam 5. An increase of one unit in log-hs-cTnT level was associated with a decrease of 0.67 (CI -1.17, -0.17) in CASI and corresponded to higher odds (OR: 1.44; CI 1.05-1.95) of cognitive decline, after adjusting for covariates. When comparing various categories of hs-cTnT with category 1, we observe that the odd of cognitive decline increases as the category increases. However, this trend does not hold for category 5 with significantly lower sample size (
Figure
).

Conclusion:
Our findings indicate an inverse relationship between hs-cTnT and cognitive function years later, which is significantly attenuated by known risk factors for cognitive decline. Further research is needed to determine hs-cTnT as a predictor of future global cognitive functions.