bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4141528: Cardiovascular and Cerebrovascular Events in Patients with Inflammatory Bowel Disease Initiating Tofacitinib, Vedolizumab, Ozanimod, or Ustekinumab: A Propensity Score-matched Cohort Study in the United States
Authors: Chen Sheng-Yin , Hsieh Yi-Jin , LU Chuan , Liao Ting-Wei Ernie , Wei Cheng-Chung
Published: November 2024

Background:
Patients with IBD exhibit elevated risk of cardiovascular and cerebrovascular events. While anti-inflammatory medications such as 5-amiosalicylic acids (5-ASA) and TNF-α antagonists are associated with reduced ischemic heart disease (IHD) risk, recent concerns about newer drugs like tofacitinib have been raised by the FDA. This study evaluates the cardiovascular and cerebrovascular risks associated with newer agents including tofacitinib, vedolizumab, ozanimod, and ustekinumab.

Goals:
To assess and compare the risks of IHD, acute myocardial infarction (AMI), and cerebrovascular accidents/transient ischemic attacks (CVA/TIA) among patients treated with newer IBD agents versus those treated with traditional TNF-α antagonists.

Methods:
This retrospective cohort study utilized the TriNetX network comprising over 60 health care organizations in the US. Eligible patients were those aged over 15, diagnosed with IBD following the FDA approval dates for each studied newer agents (tofacitinib, vedolizumab, ozanimod, and ustekinumab). We excluded patients with prior diagnoses of IHD, AMI, CVA/TIA, cardiomyopathies, heart failure, atrial fibrillation, or cerebral insults. A 1:1 propensity score-matching (PSM) method was employed to adjust for baseline characteristics. We matched IBD patients using all newer agents individually to IBD patients using TNF-α antagonists (Etanercept, Adalimumab, or Infliximab). Cox proportional hazard regressions were applied to compute the hazard ratios (HR) and 95% confidence intervals (CI) for IHD, AMI, and CVA/TIA events. Patients were followed-up until June 4, 2024 or the development of events, whichever came first.

Results:
Patients treated with tofacitinib, vedolizumab, and ozanimod showed no significant increased risk of IHD, AMI, or CVA/TIA compared to TNF-α antagonist users. Notably, ustekinumab users demonstrated a decreased risk for these events. Detailed data were shown in
Table 1
.

Conclusion:
Newer medications such as tofacitinib, ozanimod, and vedolizumab do not increase cardiovascular or cerebrovascular risks in IBD patients. Ustekinumab may offer protective benefits against such risks, indicating its potential utility in managing elevated cardiovascular risks among these patients.
Abstract 4141534: Burden of coronary artery disease predicts mortality in ischaemic stroke patients: The Norwegian Stroke in the Young Study
Authors: Jibril Khuluud Abdi , Nawaz Beenish , Waje-Andreassen Ulrike , Naess Halvor , Fromm Annette , Ali Abukar , Larsen Terje Hjalmar , Bleie Øyvind , Kuiper Kier Jan , Saeed Sahrai
Published: November 2024

Background and purpose:
Earlier European studies in young stroke patients have identified coronary artery disease (CAD) as a contributor to mortality. In the present Norwegian Stroke in the Young Study (NOR-SYS) sub-study we aim to investigate the true prevalence of CAD and the impact on mortality and event-free survival in young and middle-aged stroke survivors.

Methods:
Between September 2010 and December 2015, a total of 385 patients (15-60 years) with ischemic stroke were included. Clinical characteristics, echocardiographic and coronary imaging (angiography or cardiac CT) data, and arterial stiffness indices (pulse wave velocity, carotid intima media thickness and femoral plaque) were analysed. No CAD was defined as no history of CAD and no femoral artery plaque on vascular ultrasound (US) or negative coronary imaging. Coronary imaging was done if history of CAD or femoral plaque on US.

Results:
Mean (±SD) age was 49.6 (±9.7) year, 68.1% males. The overall prevalence of CAD was 25.2% (n=97) (non-obstructive 9.6% [n=37] and obstructive 15.6% [n=60]). In a subsample of patients (n=58) without a previous history of CAD or symptoms, who underwent cardiac CT as part of screening following femoral plaque on US, 46% (n=27) had non-obstructive CAD and 28% (n=16) had obstructive CAD. When further classified 17.2% had one-vessel disease, 3.4% two-vessel disease and 6.9% three-vessel disease. During a mean (±SD) follow-up of 9.8 (±2.5) years, 35 patients (9.1%) died (3.1% one-year mortality) and 83 (21.6%) reached a composite endpoint of new stroke, myocardial infarction or death, while 63 (16.4%) reached a composite endpoint of new stroke or death. In a Kaplan-Meier curve event-free survival was significantly lower in patients with CAD versus no-CAD (Figure). This was confirmed by multivariate cox regression models, in which CAD was an independent predictor of all-cause mortality (HR 2.25; 95% CI 1.07-4.47, p= 0.033) and composite endpoint of death or recurrent ischemic stroke (HR 3.26; 95% CI 1-47-7.23, p=0.004) adjusted for potential confounders.

Conclusions:
In the present study of young and middle-aged ischemic stroke survivors, a quarter of patients had CAD. In patients without previous history of CAD or symptoms who underwent cardiac CT on the basis of femoral plaque on US, nearly a half had non-obstructive and one-third obstructive CAD. CAD, and in particular obstructive CAD, was a major independent predictor of mortality and recurrent stroke.
Abstract 4141539: Impact of Left Ventricular End-Diastolic Diameter on the Prognosis in Patients with Atrial Fibrillation and Acute Coronary Syndrome or Undergoing PCI
Authors: Xu Wei , Yang Yan-min
Published: November 2024

Introduction:
Atrial fibrillation (AF) is a common cardiac arrhythmia, the risk of cardiovascular adverse outcome rises when it coexists with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Studies have shown that an increased left ventricular end-diastolic diameter (LVEDD) is associated with worse outcomes in various cardiovascular conditions, including heart failure, and coronary artery disease (CAD). In patients with AF, an enlarged LVEDD may indicate underlying left ventricular dysfunction and structural heart disease, which could potentially predispose to myocardial fibrosis if patients are combined with ACS. Therefore, it is essential to research the impact of LVEDD on the prognosis of patients combined with AF and ACS or PCI.

Hypothesis:
We hypothesized that LVEDD could be a risk factor for adverse outcomes in AF patients with ACS/PCI.

Aims:
This study aimed to explore the impact of LVEDD on the major adverse cardiovascular events (MACEs) in patients with AF and ACS or undergoing PCI.

Methods:
This study consecutively included a total of 2,182 patients with atrial fibrillation combined with ACS or undergoing PCI from 2017 to 2019. The primary endpoint was MACEs, which represented a composite event of all-cause death, stroke, systemic embolism, and massive hemorrhage.

Results:
The 2,182 patients were divided into two groups: LVEDD＞60mm group (n=370) and LVEDD ≤60 mm group (n=1812). During a median follow-up of 36 months, patients in LVEDD＞60 mm group had a higher incidence of MACEs ( 39.7% vs. 26.0%), Compared with the LVEDD ≤60 mm group. The Kaplan-Meier curves (Figure 1) compared by the log-rank test showed that patients with LVEDD＞60 mm were associated with a higher risk of MACEs (P＜0.001). In Table 1, LVEDD as a continuous variable and LVEDD＞60 mm was independently associated with increased risk of MACEs after adjusting age, sex, BMI, AF type, CAD type, PCI, coronary artery bypass graft, prior myocardial infarction, prior heart failure, prior hypertension, prior diabetes mellitus, troponin I, antiplatelet drugs, anticoagulant drugs, statins in Model 3. The restrictive cubic spline in Figure 2 showed that LVEDD greater than 60 mm increased the risk of MACEs. An LVEDD less than 60 mm seemed to be safe for such patients.

Conclusions:
LVEDD can be a predictor for MACEs in patients with AF combined with ACS or undergoing PCI. Furthermore, left ventricular dilation indicates a worse prognosis for these patients.
Abstract 4141553: CD38 Deficiency Increases NAD Levels And Improves Pulmonary Hypertension
Authors: Naidu Samisubbu , Thompson Katie , Tang Haiyang , Chini Eduardo , Desai Ankit
Published: November 2024

Background&Hypothesis:
Nicotinamide adenine dinucleotide (NAD) is a critical coenzyme, essential for a variety of cellular processes. Pulmonary arterial hypertension (PAH) is associated with impaired metabolism and reduced NAD levels that contribute to its hyperproliferative state. CD38 is an ecto-enzyme that degrades NAD and produces several byproducts including cyclic ADPR. We hypothesized that CD38 mediates pathological reductions in NAD levels contributing to PAH vascular remodeling.

Methods:
To test this hypothesis, we evaluated expression levels of CD38 across PAH tissues, tested its functional role in human pulmonary artery endothelial cells (PAEC) and smooth muscle cells (PASMCs), and examined the response of a global
CD38
knockout mouse (
CD38
-/-
) in an established chronic hypoxic (10% FiO2, 4 weeks) model of pulmonary hypertension.

Results:
CD38 expression was elevated in human PAECs derived from PAH cases and in rodent whole lung homogenates. Media from PAEC exposed to a CD38 inhibitor (78c) led to reduced PASMC proliferation.
CD38
-/-
mice exposed to chronic hypoxia exhibited attenuated PH compared to cage controls. Specifically, histological assessment of murine lungs revealed reduced PA medial thickness compared to control.
CD38
-/-
mice exhibited reduced right ventricular systolic pressure and a corresponding decrease in Fulton Index after hypoxic exposure. Consistent with these results, targeted metabolite measurements revealed that
CD38
-/-
mice exhibited elevated NAD levels in the lungs.

Discussion:
These results suggest that CD38 is a novel PAH target, and its deficiency restores NAD levels in the lungs and reduces pulmonary hypertension in mice.
Abstract 4141557: Does Copayment for Cardiac Rehabilitation Impact Attendance? An Analysis from the American Association of Cardiovascular and Pulmonary Rehabilitation Registry
Authors: Pack Quinn , Naser Maryam , Farah Michel , Zhang Yu , Howard George
Published: November 2024

Introduction:
Improving cardiac rehabilitation (CR) attendance is a national priority. However, insurance companies often charge copays for CR, and patients commonly report copays as a barrier to attendance.

Aim:
To describe the prevalence of copays, their amounts, and the associations with attendance and drop-out in a national sample.

Methods:
We analyzed the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) registry through the AACVPR Data Analytic Center. We included patients from 2012 to 2021 who had a value for copayment (including 0) and excluded patients with missing copay data. We described copay magnitude, prevalence, and associations with baseline factors, patient characteristics, region, and if copays were cited as a reason for drop out. In multivariable models, we analyzed if a copay of any amount was associated with CR attendance and if a dose-response existed. In all models, we adjusted for age, education, AACVPR risk category, surgical diagnosis, tobacco use, distance to CR, insurance, and median household income.

Results:
Among 489,507 total patients, 59838 were included in analyses, of which 16339 (27.3%) had a copay. Patients with copays had lower educational attainment and were more likely to have Medicare or Medicaid insurance. The median (IQR) copay was $24 (20, 34). Medicare, Medicaid, Private, and Other insurances charged a median (IQR) copay of $20 (20-25), $3.7 (3, 12), $30 (20-40), and $25 (20 to 36), respectively. Copays were more common in Florida, New York, and the Rocky Mountain States, (>40% of patients) and more expensive in the northeast (median >$34). In multivariable models, the presence of a copay was associated with attendance at 5 (4.3 to 5.6, p < 0.001) fewer sessions of CR. When considering copay amount, every $10 increase in copay was associated with 0.5 (0.4 to 0.6, p < 0.001) fewer sessions of CR. Finally, copays were cited as the reason for early drop out in 21% of cases, with 2.2 (p<0.001) fewer sessions of CR compared to drop out for other reasons.

Conclusion:
In this national sample, copays for CR are common, costly, and associated with fewer sessions of CR. Policy makers should reconsider these policies to promote CR participation.
Abstract 4141578: Clinical Determinants and Prognostic Significance of Angiopoietin-like Protein 3 in Patients with Cardiovascular Disease
Authors: Tanaka Hiroki , Matsuura Yunosuke , Moribayashi Kohei , Yamamoto Kinuko , Komaki Soichi , Yamaguchi Masashi , Ideguchi Takeshi , Kaikita Koichi
Published: November 2024

Background:
Angiopoietin-like protein 3 (ANGPTL3) has garnered attention as a target for managing clinical lipid profiles. However, the determinants of blood ANGPTL3 levels and their prognostic significance in cardiovascular disease (CVD) remain unclear.

Aims:
This study aimed to investigate the clinical determinants and prognostic significance of serum ANGPTL3 levels in patients with CVD.

Methods:
A total of 311 patients with CVD (mean age 71 years, 61% male, mean body mass index 24 kg/m
2
, 42% diabetic, median estimated glomerular filtration rate (eGFR) 57 mL/min/1.73 m
2
, 152 patients with ischemic heart disease, 75 with valvular heart disease, 30 with cardiomyopathy, 54 with other CVD) were enrolled. Serum ANGPTL3 levels were measured using an enzyme-linked immunosorbent assay (R&D Systems) and analyzed for associations with clinical characteristics and the incidence of major adverse cardiovascular events (MACE), including all-cause mortality, non-fatal myocardial infarction, heart failure hospitalization, and ischemic stroke during a one-year follow-up.

Results:
Serum ANGPTL3 levels were significantly higher in females than in males (92 [78-112] vs. 74 [56-94] ng/mL, p < 0.0001). These levels showed positive correlations with age and the levels of CRP and BNP, while negative correlations were observed with eGFR, total bilirubin (T-bil), alanine aminotransferase (ALT), albumin (Alb), hemoglobin (Hb), and platelet counts. No association was found with lipid profiles or specific CVD etiologies. Multivariate analysis identified gender, CRP, eGFR, ALT, and Hb levels as independent determinants of serum ANGPTL3 levels. During the follow-up period, 30 patients developed cardiovascular events, and receiver operating characteristic curve analysis identified a serum ANGPTL3 cutoff of 90.7 ng/mL for optimal event discrimination. Kaplan-Meier analysis showed a significantly higher incidence of MACE in patients with ANGPTL3 levels above the cutoff than those below (log-rank test, p = 0.0013). Multivariate Cox regression analysis identified elevated ANGPTL3 level as an independent determinant of MACE (hazard ratio: 1.01; 95% confidence interval: 1.00-1.02; p = 0.018).

Conclusions:
In patients with CVD, serum ANGPTL3 levels, determined by gender, inflammation, liver and renal function, and anemia, can discriminate populations at high risk of developing future cardiovascular events.
Abstract 4141581: Surgical revascularization of ischemic heart failure: a comparison between patients with preserved (HFpEF) and reduced ejection fraction (HFrEF).
Authors: Garatti Andrea , Scarpanti Matteo , Gastino Elisa , DOvidio Mariangela , Canziani Alberto , Daprati Andrea , Buratti Stefano , Rusconi Francesca , de Vincentiis Carlo , Guazzi Marco , Parolari Alessandro , Menicanti Lorenzo
Published: November 2024

Introduction:
Despite surgical myocardial revascularization(CABG) in patients with ischemic HF and reduced EF(HFrEF) is strongly supported, there is only limited evidence to guide revascularization in patients with HF and preserved EF(HFpEF).

Research Questions:
Should CHF be considered an independent risk-factor in patients undergoing CABG, irrespectively of preoperative LVEF?

Aims:
To determine the prognostic role of preserved versus reduced EF on the outcomes of patients with ischemic HF undergoing CABG.

Methods:
Between 2005-2019, 4079 consecutive patients with multivessel CAD underwent isolated, on-pump CABG at a single institution. Preoperative CHF was ascertained according to clinical symptoms, laboratory values and medical therapy. Preserved LV function was defined as EF≥50%. Accordingly, the study population was divided into 4 groups: Group I [NoHFpEF,2663 pts(65%)], Group II [HFpEF,214 pts(5%)], Group III [NoHFrEF,970 pts(24%)], and Group IV [HFrEF,232 pts(6%)]. A deterministic record linkage with the National Health Institute Database allowed unique identification of long-term mortality and major adverse cardiovascular events[acute MI, repeated PCI and HF admission(MACE)].

Results:
Patients with HFpEF presented with a similar preoperative clinical profile compared to NoHF patients, while the incidence of comorbidities significantly increased through reduced EF groups. Completeness of revascularization was consistent across the study groups. Perioperative morbidity was similar between HFpEF and NoHF patients, but progressively increased in reduced EF groups. Moreover, 30-day mortality was comparable between HFpEF and Group I(1.4%vs1.2%, P=NS), but significantly increased in Group III(3.1%) and IV(5.6%,

p<0.01

). Finally, HFpEF showed a 10-years survival comparable to Group III(63%vs61%, p=NS) but significantly reduced to Group I(75%,

p<0.01

). On the contrary, 10-year freedom from MACE was comparable between HFpEF and Group I(60%vs 67%, p=0.34), and significantly higher than Group III and IV(47% and 38% respectively,

p<0.01

–
Figure1
).

Conclusions:
HFpEF patients undergoing CABG showed comparable perioperative results to non-HF patients and significantly better long-term outcomes compared to HFrEF patients.
Abstract 4141596: Machine Learning Model Predicting In-Hospital Mortality for Cardiogenic Shock
Authors: Kochar Ajar , Foote Henry , Ratliff William , Balu Suresh
Published: November 2024

Background:
Cardiogenic shock *CS) confers a high mortality (30-50%). A key limitation of existing CS mortality models is the reliance on static parameters measured at admission which ignore the rapidly evolving natural history of CS.

Hypothesis: A machine learning (ML) model that incorporates time series electronic health record (EHR) data including echocardiogram reports and invasive hemodynamics will accurately predict mortality in patients with cardiogenic shock

Methods:
Patients with an ICD-10 code of cardiogenic shock were identified using electronic health data (EHR) from 2015 - 2019. The primary outcome was a composite of in hospital mortality or discharge to hospice. We incorporated EHR data obtained within the first 24 hours of admission including demographics, comorbidities, vital signs, lab values, medication administration, use of mechanical circulatory support (MCS), echocardiogram data, electrocardiogram reports, and hemodynamics from pulmonary artery catheter or right heart catheterization. For dynamic values such as lab values we incorporated six hour, 12 hour, and 24 hours trends as well as maximum and minimum values. We used a LightGBM model with 70/10/20 split for training, hyperparameter fine-tuning, and testing.

Results:
We identified 5,048 total admissions. Median age was 65 years (IQR 52, 72) and 64% were male. Twenty five percent presented with acute myocardial infarction and 12% with cardiac arrest. The MCS distribution was: 17% intra-aortic balloon pump and 6% VA-ECMO. All-cause mortality was 32%. Our model demonstrated robust discrimination (AUROC 0.804), precision (0.699), and calibration (expected calibration error 3.2%). The five highest importance features were age at admission, mean serum albumin, mean glascow coma score, mean platelet value in the first six hours of admission, and total urine output. Our model performed favorably to a previously developed cardiogenic shock mortality risk scores (IABP SHOCK II: AUROC 0.71, AUPRC 0.55 in our cohort).

Conclusion:
This ML CS mortality model incorporating dynamic, time series EHR data capturing the trajectory of CS in the first 24 hours after amission has high precision and discrimination. This ML model could be readily embedded into EHR systems to allow for rapid risk statification at the bed-side.
Abstract 4141606: Is 70% Achievable? Hospital-Level Variation in Rates of Cardiac Rehabilitation Use among Medicare Beneficiaries
Authors: Pack Quinn , Keys Taylor , Priya Aruna , Pekow Penelope , Keteyian Steven , Thompson Mike , D'Aunno Thomas , Lindenauer Peter , Lagu Tara
Published: November 2024

Background:
Hospitalization is an opportunity to refer and recruit eligible patients to cardiac rehabilitation (CR). Despite national goals to enroll 70% of CR-eligible patients, enrollment remains low, and little is known about how hospitals influence CR enrollment at the national level.

Methods:
We included fee-for-service Medicare beneficiaries older than 65 years who were hospitalized in 2017 for acute myocardial infarction (AMI), coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or heart valve repair/replacement. We examined the role of the hospital in CR enrollment using three different methods: 1.) a risk-standardized model to assess comparative hospital rates with bootstrap methods to group hospitals as above, at, or below national rates of CR (as might be done for quality incentives); 2.) a linear regression model to identify hospital factors associated with rates of risk-standardized CR; and 3.) a hierarchical generalized linear model to allow calculation of the hospital Median Odds Ratio (MOR).

Results:
At 3,420 hospitals, we identified 264,970 eligible patients. While a minority of hospitals (1,446; 38%) performed cardiac surgery, these hospitals cared for the vast majority (242,875; 92%) of all eligible patients, and subsequent analyses were limited to these hospitals. The median risk-standardized CR enrollment rate was low (22%) and varied 10-fold across hospitals at the 10
th
and 90
th
percentiles (3%, 42%). Bootstrap methods to group hospitals as above, at, or below national average demonstrated that about one-fifth of hospitals [301, 21%] had worse performance than the national mean and about one-third [453, 31%] had better performance than the national mean. Factors associated with higher hospital performance were Midwest location, higher number of hospital beds, directly affiliated CR program, and <1 mile distance between the hospital and closest CR facility. The national hospital MOR was 2.1, similar in effect size as Midwest location.

Discussion:
The referring hospital plays a key role in facilitating CR enrollment after discharge, Fewer than 1% of US hospitals achieved a risk-standardized CR enrollment rate of >70%. Hospitals with cardiac surgery capability care for more than 90% of all CR-eligible patients, and may be a logical place to focus improvement efforts.
Abstract 4141616: The Prognostic Role of Dynamic Cardiopulmonary Exercise Testing Variables: Assessing for Myocardial Reserve to Improve Risk Stratification
Authors: Olaya Stephan , Cochran Matthew , Acosta Mary , Sipiora Justin , Poonawalla Maria , Siddiqi Umar , Hoang Ryan , Kanelidis Anthony , Gozdecki Leo , Kalantari Sara , Swat Stanley , Belkin Mark , Grinstein Jonathan
Published: November 2024

Background:
Cardiopulmonary exercise testing (CPET) remains an important test for risk assessment in ambulatory heart failure patients to identify those who may benefit from advanced therapies, such as left ventricular assist device (LVAD) or heart transplantation (HT). The prognostic strength of cardiac performance variables at peak exercise, including oxygen consumption (VO
2
), oxygen pulse (O
2
pulse) and circulatory power (CP) is known. We explored the prognostic utility of augmentation of these parameters between resting and peak stress conditions.

Methods:
We performed a retrospective analysis of ambulatory heart failure patients from the National Heart, Lung, Blood Institute funded REVIVAL and our institutional PREDICT-HF databases. Patients with heart failure that underwent CPET and ≥ 1-year of follow-up were included. The primary outcome was a composite of death, HT, or LVAD at 1-year following CPET. The absolute change (Δ) in CPET variables was defined as the difference between resting and peak values.

Results:
A total of 351 patients from PREDICT-HF (n=110) and REVIVAL (n=241) were included; mean age 58, 70% male, 31% Black, 59% non-ischemic, median NYHA functional class 3, median INTERMACS profile 6, and mean LVEF 26%. At 1-year, there were 61 events (17%), which included 20 deaths, 19 HTs, and 22 LVAD implants. The ΔVO
2
, ΔO
2
pulse, and ΔCP were all higher in the non-event group (all p<0.001). The ΔVO
2
(odds ratio [OR]) 0.92; 95% CI 0.87-0.97; p = 0.006), ΔO
2
pulse (OR 0.85; 95% CI 0.76-0.93; p = 0.001), and ΔCP (OR 0.48; 95% CI 0.31-0.70; p<0.001) were significant predictors of the primary outcome on univariate analysis. Only ΔO
2
pulse (OR 0.85 vs. 0.89) performed better on univariate analysis when compared to its peak counterpart. Peak CP (OR 0.37) remained the strongest predictor overall.

Conclusions:
The absolute change between resting and peak VO
2
, O
2
pulse, and CP were predictive of death, HT, or LVAD at 1-year. Further multivariate analysis and comparative statistics assessing the prognostic utility of augmentation of these parameters compared to isolated peak values are needed to determine clinical utility.
Abstract 4141622: Pathway between race, historic and contemporary measures of structural racism, and life expectancy in the US
Authors: Egede Leonard , Walker Rebekah , Campbell Jennifer , Linde Sebastian
Published: November 2024

Background:
A growing body of evidence highlights the role of structural racism, or the ways in which societies foster racial discrimination through mutually reinforcing systems, on cardiovascular outcomes. This study aimed to better understand this relationship using historic structural racism (historic redlining) and a novel measure of contemporary structural racism (structural racism effect index) on life expectancy, accounting for distribution of race across counties in the US.

Methods:
After combining census tract level data, the final analytic sample consisted of 15,190 census tracts across 157 counties, within 50 states including DC. Historic structural racism was defined as historic redlining using the Home Owners’ Loan Corporation (HOLC) neighborhood grades (score between 1=best and 4=redlined). Contemporary structural racism was defined using the structural racism effect index (SREI), a summary score of nine domains (built environment, criminal justice, education, employment, housing, income/poverty, social cohesion, transportation, and wealth). Life expectancy was based on the National Center for Health Statistics’ US Small-area Life Expectancy Estimates Project using 2010-2015 data. Structural equation modeling in Stata v17 was used to investigate direct and indirect relationships between race, historic structural racism, contemporary structural racism, and life expectancy in the US.

Results:
Mean life expectancy was 77.3 years and 26.7% of the US population within each census tract was Black/African American. Historic redlining (-0.06, p<0.001), contemporary structural racism (-0.61, p<0.001), and proportion of the census tract reporting Black race (-0.21, p<0.001) were directly associated with decreased life expectancy. Historic redlining was indirectly associated with decreased life expectancy via the pathway of contemporary structural racism (0.19, p<0.001). Black race was indirectly associated with decreased life expectancy through both more exposure to historic redlining (0.18, p<0.001) and higher levels of contemporary structural racism (0.56, p<0.001).

Conclusion:
Structural racism, measured using historic or contemporary measures, is associated with decreased life expectancy. Contemporary structural racism is a stronger relationship for the pathway through which Black race is associated with lower life expectancy and is a pathway through which historic residential redlining influences life expectancy.
Abstract 4141628: Prescription of Lipid-Lowering Treatments in the year following a first Atherosclerotic Cardiovascular Event: updated results from the French Nationwide Claims Database.
Authors: Cariou Bertrand , Goronflot Thomas , Duret stephanie , Pouriel Mathilde , Bastien Alexandre , Prax Julie , Leux Christophe , COSTA Nadege , BELIARD Sophie , Ferrieres Jean , Wargny Matthieu
Published: November 2024

Introduction:
Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality worldwide. Lipid-lowering therapies (LLTs) are a key element to reduce the risk of recurrence of ASCVD events. However, despite concordant guidelines, LLTs are often underused in real-life setting.

Research questions:
The aim of this study is to describe the use of LLTs and its impact on morbi-mortality in the year following a first ASCVD event.

Methods:
This retrospective study used the national health data system (SNDS), collecting health insurance claims and hospital discharge data from 99% of the French population. Incident cases in 2021 were identified, corresponding to all adults with a first ASCVD event, based on ICD-10 hospital coding. ASCVD includes coronary artery disease [myocardial infarction, unstable angina or coronary revascularization], cerebrovascular events [ischemic stroke, carotid revascularization] and peripheral artery disease (PAD) requiring artery revascularization. In patients discharged alive from the index event, longitudinal analyses were performed at 1-year from discharge to describe LLT use, occurrence of major ASCVD events and all-cause mortality.

Results:
In 2021, 195,211 newly diagnosed ASCVD cases were identified among 43,1M adults (mean age: 70.3 (±13.7) yo; 62% of male). The first ASCVD event was myocardial infarction (N=51,614) or ischemic stroke (N=52,865) in 53.5% of incident cases. The remaining 46.5% corresponded mostly to coronary revascularization procedures (N=83,910), followed by PAD (N=26,925). In-hospital mortality was 5.5% (N=10,673). In patients analyzed at 1 year (N=180,875), 16.9% did not receive any LLT. This value rose to 26.7% among patients who had no received LLT prior to the ASCVD event. After a myocardial infarction, patients were more likely to receive LLT (91.9%) compared to after an ischemic stroke (72.9%) or revascularization for PAD (68.0%). Finally, 1-year all-cause mortality was higher in non-LLT compared to LLT patients (20.9% vs 4.0%). Additional data on the recurrence of ASCVD events as a function of LLT use are currently being analyzed and will be presented at the congress.

Conclusion:
Contrary to recommendations, the underuse of LLTs after a first ASCVD event remains very high, particularly after a stroke. This is associated with a significantly higher mortality at 1 year, justifying the need to reinforce implementation of the guidelines in real life for a better management of residual lipid risk.
Abstract 4141629: Pulmonary Arterial Pruning is Associated with Increased Pulmonary Pressure and Worse Left Ventricular Systolic and Diastolic Function in Late Life
Authors: Dewanjee Aditya , Lamberson Victoria , Yang Yimin , Claggett Brian , Matsushita Kunihiro , Blaha Michael , Washko George , San Jose Estepar Raul , Shah Amil
Published: November 2024

Background:
Advanced age is associated with left ventricular (LV) remodeling and increased pulmonary pressure; both these alterations are associated with increased risk of heart failure. However, there is a lack of data regarding morphologic changes in the pulmonary vasculature underlying these associations.

Aims:
Determine the extent to which LV remodeling associates with pulmonary arterial (PA) pruning, and the relationship of PA pruning with pulmonary pressure.

Methods:
Among 2,275 participants in the community-based Atherosclerosis Risk in Communities (ARIC) study who underwent echocardiography and non-contrast chest CT at Visit 7 (2018-2019), we quantified the fraction of total pulmonary vascular area comprised of arterial vessels with diameter <5 mm (BV5/TBV) using validated image processing (Panel A). We used multivariable linear regression to assess the association of BV5/TBV with echocardiographic measures of pulmonary artery systolic pressure (PASP) and LV structure, systolic function, and diastolic function. Models were adjusted for age, BMI, eGFR, gender, race, lung volume, SBP, prevalent CAD, diabetes, atrial fibrillation, and hypertension, cumulative pack years smoked at Visit 7, and low and high attenuation areas on CT.

Results:
Mean age was 80 ±4 years, 61% were women, 22% reported Black race, and mean LVEF was 64 ±7%. Mean BV5/TBV was 0.30 ±0.08. Lower BV5/TBV – reflecting greater PA pruning – was associated with older age, male sex, Black race, and greater BMI. There was no correlation between prevalent atrial fibrillation, hypertension, CAD, or stroke and PA pruning. Greater LV volume and mass, lower LVEF, and greater left atrial volume were each associated with lower BV5/TBV (Panel B). Lower BV5/TBV demonstrated a nonlinear association with greater PASP (Panel C), with increases in PASP noted at BV5/TBV values <0.30.

Conclusions:
Worse LV systolic and diastolic function are associated with greater PA pruning, which is in turn associated with greater PASP once BV5/TBV falls below 0.30. Our findings clarify the pulmonary vascular remodeling that links cardiac dysfunction to elevated pulmonary pressure in late life and may help identify persons at particularly high risk for pulmonary hypertension.
Abstract 4141640: The Perinexal Nanodomain Within Intercalated Discs Between Isolated Cardiomyocyte Pairs Modulates Sodium Currents
Authors: Wu Xiaobo , Swanger Sharon , Poelzing Steven , Gourdie Robert
Published: November 2024

Background:
Ephaptic coupling (EpC), a form of intercellular communication between excitable cells, has been proposed to occur at the perinexus, a sodium channel-rich nanodomain within the intercalated disc (ID). Previous studies suggest that widening the perinexus can influence EpC by altering sodium ion availability, which in turn determines perinexal sodium currents (INa). However, there is a lack of direct evidence for a causal relationship between the perinexus and ephaptic coupling. This study aims to develop a novel approach to directly measure the effect of perinexal expansion on INa. We hypothesize that widening the perinexus increases INa in cardiomyocytes that maintain intact IDs.

Methods:
We selected pairs of mouse cardiomyocytes connected through IDs, preserving intact perinexi. Initially, the feasibility of measuring the whole-cell INa from the entire cell pair was investigated using single patch clamp. If feasible, widening the perinexus should increase the whole-cell INa by enhancing perinexal INa. Isolated single cardiomyocytes and cardiomyocyte pairs from ventricles were used for whole-cell INa recordings. A de-adhesion peptide named βadp1, previously demonstrated to widen the perinexus, was used.

Results:
We found that the whole-cell INa in cell pairs can be stably measured, showing no differences in INa density compared to single cells (panels A&B in Figure). Notably, the duration of the INa tracing in cell pairs is short relative to single cells primarily due to shorter inactivation phase in cell pairs (panel C), suggesting a lack of available sodium ions in the ID caused by sodium channel activation. It was also confirmed that βadp1 does not affect INa in single cells, consistent with previous reports. Importantly, we demonstrated that βadp1 significantly increased INa (panel D), likely due to faster sodium influx during sodium channel activation phase.

Conclusions:
The cell pair model is a feasible method for measuring whole-cell INa with single patch clamp, and widening the perinexus increases INa in this model, which supports the hypothesis that EpC is occurring between the cells. Our findings may offer a new approach to study the impact of structural changes in IDs on ionic currents.
Abstract 4141644: Sex Differences in Rates of Contrast-Induced Acute Kidney Injury After Percutaneous Coronary Intervention
Authors: Zhang Neil , Sherwood Kyla , Claggett Brian , Dhruva Sanket , Sandhu Ashishdeep , Cheng Susan , Ebinger Joseph
Published: November 2024

Background:
Previous studies have shown conflicting results regarding higher rates of contrast-induced acute kidney injury (CI-AKI) after percutaneous coronary intervention (PCI) among women as compared to men. We sought to identify covariates that explain possible sex differences in rates of CI-AKI after PCI.

Methods:
This was a retrospective observational cross-sectional study of all PCIs performed at Cedars-Sinai Medical Center from 2020-2023, sourced from the National Cardiovascular Data Registry. The primary outcome and regressor were CI-AKI and sex, respectively. Covariates were other patient demographics, comorbidities, procedural factors, and health insurance. We excluded patients with pre-PCI dialysis requirement or without pre/post-PCI creatinine. We used multivariable-adjusted logistic regression to evaluate rates of CI-AKI among women versus men. Using additive adjustment, we identified factors that accounted for the sex differences.

Results:
Of 2971 PCIs included, 820 (27.6%) were performed in women, 316 (10.6%) in Black patients and 283 (9.5%) in Hispanic patients. On average, women were older than men (73.9 vs 68.6 years, p<0.001). Women had higher rates of anemia compared to men (19.8% vs 10.9%, p<0.001). In bivariate analysis, women experienced more CI-AKI than men (15.0% vs 11.4%, p=0.008) with an odds ratio (OR) of 1.37. Additive adjustment with demographics reduced the OR of CI-AKI for women to 1.26, accounting for ~30% of the identified sex difference. Additional adjustment with both demographics and anemia yielded an OR for CI-AKI of 1.14, explaining ~60% of the sex difference. Adjustment with demographics and all comorbidities accounted for ~75% of the sex difference, with an OR for CI-AKI of 1.11. Further additive adjustment for procedural factors and insurance had negligible contributions. The sex difference was no longer significant after adjustment for demographics.

Conclusion:
Women undergoing PCI had higher rates of CI-AKI as compared to men, though this was no longer significant with multivariable analysis. The risk for CI-AKI for women over men was primarily contingent on demographics and comorbidities, with anemia accounting for a substantial proportion of this risk.
Abstract 4141674: Inhibiting Detrimental Cardiac Functions Using Biased Allosteric Modulators Of β
2
-Adrenergic Receptor Modulating The Canonical Signaling
Authors: Shah Sushrut , Federico Marilen , Yuan Yuexing , Shatzman Alexis , Sheu Shey-Shing , Deshpande Deepak
Published: November 2024

BACKGROUND:
Cardiac diseases such as heart failure (HF) are characterized by irregular cardiac contraction and relaxation due to repeated damage to the myocardium. β-adrenergic receptors (βAR) on cardiomyocytes (CMs) are predominant regulators of cardiac contractility and hence β-blockers are utilized in the treatment of HF. Biasing βAR-mediated signaling in CMs presents an opportunity for developing alternative therapies. We have recently discovered a new allosteric modulators (AMs) that preferentially diminish βAR-Gαs signaling, not affecting β-arrestin mediated signaling. Considering the functional significance of βAR-mediated Gαs- and β-arrestin signaling in CMs, our objective is to investigate the impact of our recently identified β
2
AR AMs on CM contractility and heart function. We
hypothesize
that Negative AMs (NAMs) of β
2
AR will inhibit the βAR-Gαs signaling induced by β-agonists thereby decreasing cardiac contractility in vitro and in vivo.

METHODS:
In isolated adult ventricular murine CMs (AVCM), we assessed the effect of NAM on isoproterenol-induced contractility and calcium transients using the IonOptix System. A subset of cells were pre-treated with β
1
AR-antagonist. To examine the effect in the whole heart, we treated perfused hearts in Langendorff Apparatus with ISO (100nM) and vehicle/NAM. Finally, to assess effects of AMs on heart functions
in vivo
, we performed electrocardiogram (ECG) and echocardiogram in mice treated with ISO.

RESULTS:
In AVCMs, ISO augmented CM contractility and calcium. Concomitant NAM treatment significantly attenuated ISO-induced cell contractility, elevation of calcium peak and decreased time-to-relaxation. Interestingly, pretreatment of CMs with β
1
AR-antagonist reversed the inhibitory effect of NAM on ISO-mediated contractility. Our
ex vivo
perfused heart experiments demonstrated an inhibition of ISO-induced cardiac contractility by the β
2
AR NAM. ECG studies demonstrated an attenuation of ISO-induced increase in parameters including heart rate and PVCs. Echocardiogram recording confirmed the decrease in heart rate and revealed alleviation of ISO-induced reduction in ejection fraction and fractional shortening and inhibition of ISO-induced isovolumic contraction time and myocardial performance index.

CONCLUSIONS:
These data collectively demonstrate that our recently discovered biased NAM could preferentially ameliorate cardiotoxic Gαs signaling and function in CMs.
Abstract 4141680: Reduced Retinal Microvascular Density in Women with Coronary Microvascular Dysfunction: A Pilot Study
Authors: Shiromani Sakshi , Al-Badri Ahmed , Lindeke-Myers Aaron , Schwartz Arielle , Vatsa Nishant , Dave Esha , Rashid Fauzia , Jain Nieraj , Mehta Puja
Published: November 2024

Introduction:
Patients with myocardial ischemia but no obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD), which may be a manifestation of systemic vascular dysfunction. The state of retinal microvasculature is linked to a variety of cardiovascular risk factors, but the relationship between CMD and the retinal microvasculature is unknown.

Research Question:
Among individuals with INOCA, are retinal microvasculature changes reflective of CMD?

Aim:
To evaluate the retinal microvasculature in women with INOCA, comparing those with and without CMD.

Methods:
Women with INOCA (N=18) who had coronary function testing to evaluate for CMD were enrolled at Emory University between 2018-2021. Participants were classified into a CMD group and a non-CMD group, with CMD defined as coronary flow reserve (CFR) <2.5 in response to adenosine. Participants underwent retinal optical coherence tomography angiography to assess the retinal microvasculature. Vessel density, perfusion density, as well as perimeter and circularity of the foveal avascular zone (FAZ) were obtained. Non-parametric statistics were used to compare the two groups.

Results:
Mean age was 54.7 (SD 12.5) years. The CMD (N=11) and non-CMD (N=7) groups were balanced with respect to age, BMI, and presence of systemic diseases including diabetes, hypertension, and hyperlipidemia. Those with CMD had a lower inner retinal vessel density [22.6(1) vs 21.2(0.5), p=0.006], lower full vessel density [21.2(0.6) vs 19.9(0.8), p = 0.008], lower inner perfusion density [41.1(0.8) vs 38.5(2.1), p=0.006] and lower full perfusion density [38.5(0.6) vs 36.1(1.8), p=0.007]. There were no differences in the FAZ perimeter or circularity between the two groups.

Conclusions:
In women with INOCA, those with CMD had a lower retinal microvascular density and perfusion density compared to non-CMD group. Direct, non-invasive, and relatively inexpensive imaging of the retinal microvasculature is feasible and may serve as a window to coronary microvascular function in women with INOCA; a larger study, including men, is needed to confirm these findings.
Abstract 4141689: Sex-based Differences of Inpatient Mortality Following Coronary Artery Bypass Grafting: Insight From Large National Database
Authors: Abood Zaid , Weiss Eric , Chiang Yuting , Lin Andrew , Sokhal Balamrit , Tunink Kirsten , Hommeida Mohamed , Bajwa Tanvir , Allaqaband Suhail , Jan M. Fuad
Published: November 2024

Background:
Female patients referred for coronary artery bypass grafting (CABG) are generally older and have more comorbidities than their male counterparts. Although higher perioperative mortality among female patients has been reported, there is a lack of large-scale, real-life data on this outcome and its trend.

Aim:
To study the mortality rate among female patients undergoing CABG from 2015-2020 and compare it with that of their male counterparts.

Methods:
The National Inpatient Sample from January 2015 to December 2020 was utilized to identify the study population using the International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification. The primary outcome was the overall in-hospital mortality of CABG based on sex, and the secondary outcome was the mortality trend between the groups.

Results:
We evaluated 929,759 patients who underwent CABG, of whom 230,000 (24.3%) were female. The female patient group was slightly older than the male patient group (66.4 vs 65.4 years, P<.001) and had a lower proportion of Caucasians (73.7% vs 79.4%, P<.001). Overall mortality among the female patients was nearly double that of their male counterparts (2.5% vs 1.4%, P<.001). Over the study period, the adjusted mortality rate declined in both sexes but remained higher in the female group (Fig. 1A). Among female patients, the mortality rate decreased from 2.5% in 2015 to 1.6% in 2019 (P<.001), then increased to 2.0% in 2020 (P=.050). The mortality rate among male patients consistently declined, from 1.9% in 2015 to 1.2% in 2020 (P<.001).

Conclusion:
This analysis reveals that female patients undergoing CABG have higher mortality rates than their male counterparts despite overall declines in mortality rates over the study period. The persistent disparity and the observed increase in mortality in female patients in 2020 highlight the need for further research to identify and address the precipitating factors of this outcome.
Abstract 4141691: Uncovering the Mechanisms by Which SGLT-2 Inhibitors Improve Cardiovascular Outcomes: A Proteomic Analysis
Authors: Hamze Jad , Harris Dwight , Stone Christopher , Broadwin Mark , Kanuparthy Meghamsh , Sabe Sharif , Abid Ruhul , Sellke Frank
Published: November 2024

Introduction:
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to improve cardiovascular outcomes, as evidenced by their inclusion as a preferred treatment option in the ACC/AHA/HFSA guidelines for heart failure management. However, the mechanisms underlying these benefits are not well-understood. The goal of this study is to address this gap through high-sensitivity proteomic analyses to characterize the specific molecular pathways affected by SGLT-2 inhibitor canagliflozin (CAN) administration in a large animal model of coronary artery disease and metabolic syndrome.

Methods:
Twenty-one six-week-old Yorkshire swine were fed a high-fat diet for induction of metabolic syndrome, after which chronic myocardial ischemia was induced by placing an ameroid constrictor around the left circumflex coronary artery. Two weeks later, the swine either received no drug (CON n=11) or 300mg of CAN daily (n=10). Treatment lasted for five weeks, after which myocardial tissue from both ischemic and non-ischemic regions was collected and sent for proteomic analysis.

Results:
Proteomic analysis identified a total of 2855 common proteins between ischemic and nonischemic CAN groups. The CAN ischemic group had 124 upregulated and 111 downregulated proteins as compared to CON; pathway analysis applied to this data yielded upregulation of oxidative phosphorylation and respiratory electron transport, as well as downregulation of glycolysis and the pentose phosphate pathway. The CAN nonischemic group had 121 upregulated and 25 down regulated proteins as compared to the CON group. Pathway analysis showed that of the up- and downregulated proteins, significant alterations included upregulation of oxidative phosphorylation and downregulation of gluconeogenesis and glycolysis.

Conclusion:
CAN treatment in both ischemic and nonischemic myocardial tissue upregulates oxidative phosphorylation and downregulates glycolysis in a clinically relevant large animal model. These changes ameliorate metabolic derangement in the ischemic myocardium and provide further mechanistic insights into the molecular function of SGLT-2 inhibitors in ischemic heart disease.