bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4113300: Targeting Liver Epsins Ameliorates Dyslipidemia in Atherosclerosis
Authors: Zhu Bo , Gupta Krishan , Cui Kui , Malovichko Marrina , srivastava sanjay , Chen Kaifu , Shi Jinjun , Chen Hong
Published: November 2024

Rationale:
Low density cholesterol receptor (LDLR) in the liver is critical for the clearance of low-density lipoprotein cholesterol (LDL-C) in the blood. In atherogenic conditions, proprotein convertase subtilisin/kexin 9 (PCSK9) binds to LDLR on the surface of hepatocytes, preventing its recycling and enhancing its degradation in lysosomes, resulting in reduced LDL-C clearance. Our recent studies demonstrate that epsins, a family of ubiquitin-binding endocytic adaptors, are critical regulators of atherogenicity. Given the fundamental contribution of circulating LDL-C to atherosclerosis, we hypothesize that liver epsins promote atherosclerosis by controlling PCSK9-triggered LDLR endocytosis and degradation.

Objective:
We will determine the role of liver epsins in promoting PCSK9-mediated LDLR degradation and hindering LDL-C clearance to propel atherosclerosis.

Methods and Results:
We generated double knockout mice using albumin Cre in which both genes of epsin, namely, epsin 1 and epsin 2, are specifically deleted in the liver (Liver-DKO) on an ApoE
-/-
background. We discovered that western diet (WD)-induced atherogenesis was greatly inhibited, along with diminished blood cholesterol and triglyceride levels. Mechanistically, using scRNA-seq analysis on hepatocyte-derived data revealed elevated pathway involved in LDL particle clearance under WD treatment in ApoE
-/-
/Liver-DKO, which was coupled with diminished plasma LDL-C levels. Further analysis using the MEBOCOST algorithm revealed enhanced communication score between LDLR and cholesterol, suggesting elevated LDL-C clearance in the ApoE
-/-
Liver-DKO mice. In addition, we showed that loss of epsins in the liver upregulates of LDLR protein level. We further showed that epsins bind LDLR via the ubiquitin-interacting motif (UIM), and PCSK9-triggered LDLR degradation was abolished by depletion of epsins, preventing atheroma progression. Finally, our therapeutic strategy, which involved targeting liver epsins with nanoparticle-encapsulated siRNAs, was highly efficacious at inhibiting dyslipidemia and impeding atherosclerosis.

Conclusions:
Liver epsins promote atherogenesis by mediating PCSK9-triggered degradation of LDLR, thus raising the circulating LDL-C levels. Targeting epsins in the liver may serve as a novel therapeutic strategy to treat atherosclerosis by suppression of PCSK9-mediated LDLR degradation.
Abstract 4113420: Assessing the Clinical Impact of Cardiac Intensivists in Cardiac Intensive Care Units.: Results from the RESCUE registry
Authors: Bae Dae-Hwan , Bae Jang-whan , Lee Junyoung , Sun jonghee , Lee Sang Yeub , Yang Jeong Hoon , Gwon Hyeon-Cheol
Published: November 2024

Background:
Presence of dedicated intensive care unit physicians is associated with reduced intensive care unit mortality. However, there is limited information regarding the impact of cardiac intensivists in cardiac intensive care units.

Research Questions:
What is the role of cardiac intensivists in influencing clinical outcomes for adult patients admitted to cardiac intensive care units?

Aims:
To investigate the association between cardiac intensivist-directed care and clinical outcomes in adult patients admitted to cardiac intensive care units.

Methods:
This retrospective study used data from the SMART-RESCUE registry, which is a multicenter, retrospective, and prospective registry of patients presenting with cardiogenic shock. The study involved 1,247 patients enrolled from January 2014 to December 2018 at 12 tertiary centers in Korea. These patients, who were suffering from cardiogenic shock, were divided into two groups depending on whether their care involved a cardiac intensivist.

Results:
The study found that the all-cause mortality rate was 33.6%. The in-hospital mortality rate was significantly lower in the group managed by cardiac intensivists (25.4%) compared to the group without (40.1%). Similarly, cardiac death rates were lower in the cardiac intensivist group (20.5%) than in the non-cardiac intensivist group (35.4%). In patients undergoing extracorporeal membrane oxygenation, mortality at centers with cardiac intensivists was 38.0%, compared to 62.2% at centers without. The use of dopamine was lower and norepinephrine use was higher and the vasoactive-inotropic score was lower in the cardiac intensivist group.

Conclusion:
Cardiac intensivist involvement in patient care within cardiac intensive care units was associated with a reduction in in-hospital mortality and administration of vasopressors and inotropes according to cardiogenic shock guidelines, indicating a beneficial effect on clinical outcomes.
Abstract 4113573: Long Noncoding RNAs to Predict COVID-19 Neuro-Cardio-Vascular Outcomes
Authors: Vausort Melanie , Boubakeur Hassina , Zhang Lu , Fagherazzi Guy , Ollert Markus , Devaux Yvan
Published: November 2024

Introduction/Background:
Cardiovascular and neurological diseases develop in a significant proportion of COVID-19 patients. Minimally invasive tools to predict outcome after SARS-CoV-2 infection would enable personalized healthcare, potentially easing the disease burden. We showed that blood levels of the long noncoding RNA lymphoid enhancer-binding factor-1 antisense 1 (LEF1-AS1) predict COVID-19 in-hospital mortality.

Hypothesis:
LEF1-AS1 is associated with long-term clinical outcomes of COVID-19.

Aim:
Test the capacity of LEF1-AS1 to predict neuro-cardio-vascular outcomes post-SARS-CoV-2 infection.

Methods/Approach:
We enrolled 104 primo-infected COVID-19 patients aged 18+ recruited from April to December 2020 in the PrediCOVID national cohort for which 12-month follow-up data were available (Ethics Committee approvals 202003/07 and 202310/02-SU-202003/07). Whole blood samples were collected at baseline and expression levels of LEF1-AS1 were assessed by quantitative PCR.

Results/Data:
Of the 104 patients, 35 had at least one neurological symptom and one cardiovascular symptom at month 12. Levels of LEF1-AS1 at baseline were lower (p=0.019) in patients who developed neurological and cardiovascular symptoms as compared to patients who did not. Lower LEF1-AS1 was associated with symptoms development with an odds ratio of 0.48 (95% CI 0.28-0.83) from logistic regression model adjusted for age, sex, comorbidities and disease severity at baseline. Addition of LEF1-AS1 to a clinical model including age, sex, comorbidities and baseline severity yielded an incremental predictive value as attested by an increased AUC from 0.79 to 0.83 (likelihood ratio test p=0.005), a net reclassification index of 0.54 (p=0.007) and an integrated discrimination improvement of 0.08 (p=0.009).

Conclusion:
Blood levels of LEF1-AS1 predict 12-month neurological and cardiovascular outcomes of COVID-19 patients. This needs to be validated in larger populations.
Abstract 4113716: Natural shear wave imaging as a predictor for left ventricular pressures: Can they reflect raised filling pressures?
Authors: Youssef Ahmed , Desmet Walter , Castaldi Gianluca , Frederiks Pascal , Dhooge Jan , Voigt Jens-Uwe
Published: November 2024

Background:
Current conventional echocardiographic assessment of diastolic function relies on predicting left ventricular (LV) filling pressure as a surrogate of diastolic function. High frame rate (HFR) Shear wave (SW) imaging is emerging as an innovative parameter for assessing myocardial stiffness, a key determinant of diastolic function. Natural SW are induced by valve closure (i.e. mitral valve closure (MVC)). Little is known so far, to which extent SWs could reflect changes in diastolic LV filling pressures.

Purpose:
We aimed at investigating the relationship between natural SW after MVC and LV diastolic pressures in an attempt to set up a cut-off value beyond which, elevated LV pressure can be suspected indicating diastolic dysfunction.

Methods:
Thirty patients (mean age 68.4±9.9 years) scheduled for clinically indicated left heart catheterization were prospectively recruited. Left ventricular end-diastolic pressure (LVEDP) was measured during the catheterization. Immediately afterwards, conventional as well as HFR (1167 ±86 Hz) echocardiography was performed. We drew an anatomical M-mode along the anteroseptal wall in the parasternal long axis view from base to apex and the display was colour coded for tissue acceleration. SWs appeared immediately after MVC as tilted green bands and their propagation velocity was measured semi-automatically
(Figure 1)
.

Results:
LVEDP in our cohort ranged from 7.5 to 29.5 mmHg. From conventional echocardiographic parameters, only mitral inflow to mitral relaxation velocity ratio (E/e’) correlated moderately with LVEDP (r=0.51, p=0.006). SW velocities after MVC showed strong positive correlation with LVEDP (r=0.78, p<0.001)
(Figure 2)
. A cut-off value for SW velocity of 5.8 m/s showed an excellent ability to discriminate normal from elevated LVEDP (AUC: 0.98; Sensitivity: 90%, specificity: 100%, accuracy: 97%)
(Figure 3)
.

Conclusions:
Our data showed that SW velocities at end-diastole after MVC could predict elevated LV filling pressures accurately. Natural shear wave imaging appears as a promising innovative tool for assessment of diastolic function.
Abstract 4113864: Hyperkalemia In Patients With Heart Failure Correlates to Worse Inpatient Outcomes
Authors: Mohamad Alahmad Mohamad Alhoda
Published: November 2024

Background:
Heart failure (HF) is one of the leading causes of hospitalizations in the States. Hyperkalemia is not an infrequent comorbidity in patients with HF, limiting the maximum benefits of guideline-directed medical therapy. This study evaluates the outcomes in patients admitted for HF with and without hyperkalemia.

Methods:
We used the Nationwide Readmissions Database (NRD) from 2016-2019, extracting adult patients with a primary diagnosis of HF who were admitted between January and November of each year. Survey procedures were applied using SAS 9.4.

Results:
We included 4,454,273 weighted hospitalizations due to HF for which 380,446 patients (8.5%) had a concurrent diagnosis of hyperkalemia. Overall, patients with hyperkalemia, compared to HF cases with hyperkalemia, were slightly younger (mean age 70 years vs. 72 years, p <0.01) with fewer women (47% vs.48%) respectively. Patients with hyperkalemia had a higher frequency of diabetes mellitus, hypertension, chronic liver disease, acute kidney injury, chronic kidney disease, end-stage renal disease, and acute encephalopathy (p<0.001). They had more inpatient complications including ventricular fibrillation and cardiac arrest (p <0.001) with longer mean lengths of stay (7 days vs. 5 days, p <0.001) and 30-day readmissions (28% vs. 22%, p<0.001). In-hospital mortality during index admission was significantly higher in the hyperkalemic group (6.4% vs. 2.5%, p < 0.001). Inpatient outcomes including mortality were also worse during first readmission (7% vs. 6%, p<0.01). Even after adjustment for the above-mentioned comorbidities, multivariable analysis reveals that hyperkalemia is an independent factor for inpatient mortality (adjusted OR 1.9 [1.8-2], p<0.001).

Conclusion:
Hyperkalemia in patients admitted with HF is associated with increased inpatient mortality and readmission. Further studies can investigate whether novel potassium binders may improve outcomes.
Abstract 4113942: Validation of Changes in the Cutoff Values of Achilles Tendon Thickness on Radiography in the Clinical Criteria of Heterozygous Familial Hypercholesterolemia in Japan
Authors: Tada Hayato , Takeji Yasuaki , Nohara Atsushi , Kawashiri Masa-aki , Takamura Masayuki
Published: November 2024

Background:
To increase sensitivity and maintain specificity, the 2022 Japan Atherosclerosis Society familial hypercholesterolemia (FH) clinical criteria was modified. In particular, the cutoff value of Achilles tendon thickness (ATT) on radiography was changed from ≥9 mm in both men and women to ≥8.0 mm in men and ≥7.5 mm in women. The current study aimed to validate the efficacy of this modification in independent samples.

Methods:
Patients with FH were retrospectively reviewed. The proportions of patients with pathogenic FH mutation who had an ATT of <7.5/8.0 mm (group 1), ≥7.5/8.0 and <9.0 mm (group 2), and ≥9 mm (group 3) were assessed.

Results:
In total, 492 patients were included in group 1, 102 in group 2, and 263 in group 3. Approximately 14.0%, 55.9%, and 79.8% of patients in groups 1, 2, and 3, respectively, exhibited FH mutation. Further, 37.3%, 77.3%, and 86.5% of patients with a low-density lipoprotein cholesterol level of ≥180 mg/dL in groups 1, 2, and 3, respectively, harbored FH mutation. Moreover, the median low-density lipoprotein cholesterol levels (157, 182, and 253 mg/dL, respectively) and the proportion of patients with protein-truncating mutation (3.8%, 16.7%, and 53.2%, respectively) had a significant trend.

Conclusions:
There was a substantial number of patients with FH who had an ATT of ≥7.5/8.0 and <9.0 mm. These patients previously had a deferred diagnosis of FH. However, they were diagnosed with FH based on the new clinical guideline.
Abstract 4113951: Calcification Alters Luminal Surface Complexity in Cadaveric Left Anterior Descending Arteries
Authors: Chong Lionel , Husain Gazi , Magnotto John Christopher , Simha Pradyumna , Mann Shahzabe , Beatty Brian
Published: November 2024

Background:
Understanding the intricacies of luminal surface topographic changes in pathologic coronary arteries may yield insight not only on the efficacy of existing clinical interventions (e.g. impact of surface changes on stent anchoring), but also on the subsequent hemodynamic changes and pathophysiology of thrombus formation. In this study, we aim to detect and quantify luminal surface alterations induced by the presence of calcification in cadaveric left anterior descending arteries (LADs) using a novel approach–surface metrology.

Methods:
LADs (n=10) were harvested from cadaveric hearts using a systematic dissection approach, scanned using the Bruker Skyscan 1173 microCT scanner, and then underwent threshold-based image segmentation on Dragonfly by Object Research Systems to quantify the total calcium volume present throughout the vessel. Each specimen was then splayed open and up to 15 scans were performed at 20X magnification using the Sensofar S Neox optical profiler. Each scan subsequently underwent surface metrologic scale-sensitive fractal analyses in SensoMap 10.

Results:
Extent of calcification was standardized and expressed using the following ratio: total calcium volume by total vessel length (TC/VL). We considered a TC/VL ratio of 0-0.25 as low calcification and 0.26-0.5 as high calcification. Interestingly, our findings demonstrated statistically significant increases in smooth-rough crossover (SRC) and scale of maximum complexity (Smfc) with positive correlation, but reductions in fractal complexity (Lsfc) and fractal dimension (Dls) with negative correlation, in highly calcified compared to lowly calcified LADs.

Conclusions:
Our data suggests that the presence of calcium in the walls of LADs may translate to increased roughness in luminal surfaces generally, but smoothness over calcified plaques, locally. Our proposed mechanism is increased endothelial tension directly over areas of calcification, thus reducing surface complexity. Future studies will involve modeling blood flow using smooth particle hemodynamics (SPH) based on complete luminal and surface topographical geometries to evaluate the impact of these surface changes on hemodynamics.
Abstract 4113961: Contemporary Guideline Directed Medical Therapy in Heart Failure in Clinical Practice - Results from the EMPACE Study
Authors: Greene Stephen , Adam Atif , Schmedt Niklas , Carlsen Christian , Brand Milou , Brewster Jack , Karimi Leila , Prochaska Juergen H. , Tran Phuong , Seager Sarah , Alhamdow Ayman
Published: November 2024

Background:
Guideline directed medical therapy (GDMT) for heart failure (HF) evolves, incorporating newer therapies such as SGLT2i within recommendations for HFmrEF and HFpEF. Understanding the contemporary profile of real-world HF patients, in combination with real-world utilization of GDMT, is important for informing GDMT implementation and quality improvement strategies. The EMPACE study aims to improve our comprehension of HF GDMT utilization in real-world settings during post-2020
.

Objectives:
To describe baseline demographic and clinical characteristics, including baseline treatments, of patients with HF hospitalization (HHF).

Methods:
This non-interventional, retrospective cohort study used patient data standardized to the OMOP Common Data Model from the Optum Market Clarity, an integrated EHR and Claims database in the U.S. The study period spanned from Jun-2020 to Oct-2023. Adult patients with a primary diagnosis of HF during hospitalization were stratified by HF phenotypes (HFrEF, HFmrEF, HFpEF) based on left ventricular ejection fraction (EF).

Results:
A total of 30,762 patients with HHF were included (74% HFrEF, 4% HFmrEF, and 22% HFpEF). The mean age was 70.1 years, 60% were male, mean BMI was 30.6 kg/m
2
, and mean eGFR was 58.7 mL/min/1.73m
2
. Of them, 72% had a history of HF and 43% has been previously hospitalized for HF in the past 1 year. The prevalence of baseline comorbidities was as follows: hypertension (90%), coronary artery disease (54%), chronic kidney disease (38%), atrial fibrillation (40%), peripheral artery disease (9%), stroke history (9%), and end-stage renal disease (1%). Medication prior to HF hospitalization are described in the figure 1. Overall, prior comorbidities and HF medication use in the last 365 days prior to HHF were similar between all HHF patients and the HFrEF, HFmrEF, and HFpEF phenotypes, except for the lower use of MRA and ARNI in HFmrEF, and HFpEF patients.

Conclusion:
This study showed a high comorbidity burden and a low utilization of many GDMT prior to hospitalization, especially for novel GDMT (ARNI and SGLT2i) and in HFmrEF and HFpEF. Despite many medications having a varying strength of guideline recommendation depending on EF, absolute differences in rates of GDMT utilization were relatively small across the EF phenotypes. Across the spectrum of EF, further efforts are needed to improve use of GDMT and reduce the missed opportunities for GDMT implementation that are occurring prior to HHF.
Abstract 4114276: Identification of the heterogeneity in the risk of heart failure in those with left bundle branch block pattern using artificial intelligence
Authors: Yagi Ryuichiro , Deo Rahul , Macrae Calum , Goto Shinichi
Published: November 2024

Introduction:
The association between left bundle branch block (LBBB) and heart failure is well-established. However, the lack of a practical risk assessment tool for patients with LBBB poses a clinical challenge to the management despite the heterogeneity of the LBBB population.

Hypothesis:
Artificial intelligence (AI) can extract features to stratify the risk of heart failure (HF) within the heterogeneity of LBBB.

Methods:
All 12-lead ECGs diagnosed with LBBB recorded from 1/1/2015 to 12/31/2019 were identified in our institution. ECG data were analyzed as 2D matrices with a shape of 12×2500. The Uniform Manifold Approximation and Projection (UMAP) was used to visualize the heterogeneity of LBBB ECG. Additionally, a 2-dimensional convolutional neural network model was trained to detect LBBB ECGs associated with past HF diagnosis. The model was then applied to ECGs from an external cohort of patients with LBBB but without a history of HF. Cumulative incidences of HF admission were compared by stratifying according to tertiles of the model output (low, intermediate and high AI score groups)

Results:
We identified 15,124 LBBB ECGs in our institution (training dataset) and 2,463 individuals with LBBB ECGs in the external cohort (external test dataset). The UMAP projection of the ECGs revealed distinct heterogeneity in the data (
Fig A
). This heterogeneity was not fully explained by patient demographics, ECG features, or institutions. When the external cohort was divided into 3 groups according to the tertile of AI prediction, patients with high AI scores had a higher risk of HF admission (high vs low AI score group: hazard ratio (HR), 2.10; 95% confidence interval (CI), 1.66-2.65; intermediate vs low AI score group: HR, 1.39; 95%CI, 1.08-1.78: log-rank p <0.0001;
Fig 1B
). This finding was unchanged after adjusting for multiple clinical characteristics and ECG parameters, including QRS duration.

Conclusion:
We observed significant heterogeneity in ECGs presenting LBBB, and the AI model excellently stratified the risk of heart failure admission in patients with LBBB from a single recording of 12-lead ECG, suggesting great potential for clinical utility in managing patients with LBBB.
Abstract 4114406: Galectin-3 and Progression of Kidney Disease in Patients With Type 2 Diabetes Mellitus: Analyses From the DECLARE-TIMI 58 Trial
Authors: Haller Paul , Wiviott Stephen , Berg David , Jarolim Petr , Goodrich Erica , Bhatt Deepak , Cahn Avivit , Gause-Nilsson Ingrid , Leiter Lawrence , McGuire Darren , Raz Itamar , WILDING JOHN , Sabatine Marc , Morrow David
Published: November 2024

Background:
Galectin-3 (Gal-3) is a circulating biomarker of fibrosis, with higher levels having been associated with an increased risk of progression of kidney disease. Patients with type 2 diabetes mellitus (T2DM) are at increased risk for kidney disease with fibrosis.

Aims:
To study the association of Gal-3 with chronic kidney disease progression, and the effect of the SGLT2-inhibitor dapagliflozin in pts with T2DM.

Methods:
DECLARE-TIMI 58 was a randomized, placebo-controlled trial of dapagliflozin in pts with T2DM with or at high risk for atherosclerotic cardiovascular (CV) disease and creatinine clearance ≥60ml/min. In a nested biomarker substudy, Gal-3 was measured at baseline (Alinity, Abbott Diagnostics) in the TIMI Clinical Trials Laboratory (Boston, MA). The prespecified kidney-specific composite endpoint (Kidney-EP) was a sustained ≥40% decrease in eGFR to <60 mL/min, initiation of renal replacement therapy or confirmed sustained eGFR <15 mL/min, or adjudicated renal death. Cox models were adjusted for baseline eGFR, urine albumin-creatinine ratio (UACR), patient characteristics, CV risk factors, NTproBNP and hs-cTnT.

Results:
Among 14,530 pts, median Gal-3 was 14.9 ng/mL [IQR, 11.9, 18.4]. Gal-3 was weakly associated with UACR (r = 0.098, p < 0.0001) and eGFR (r = -0.27, p<0.001) at baseline. Gal-3 was independently associated with the incidence of the Kidney-EP (adj-HR 1.15 [95% CI 1.03, 1.28] per 1-SD log(Gal-3), p = 0.013). Upon stratification by quartiles, there was a gradient of higher adjusted risk of the Kidney-EP with higher Gal-3 (
Fig., A
; p-trend <0.0001). There were 111 (1.5%) and 203 (2,8%) Kidney-EPs in the dapagliflozin and placebo groups, respectively. Dapagliflozin significantly and similarly reduced the relative risk of the Kidney-EP across quartiles of Gal-3 (overall HR 0.45 [95%CI 0.23, 0.85], p<0.0001; p-interaction = 0.97,
Fig., B
). However, there was greater absolute benefit of dapagliflozin with higher Gal-3 (ARR Q4 1.9 [95% CI 0.6, 3.2] vs. Q1 0.6% [-0.1, 1.3], ARR p-trend 0.048).

Conclusion:
Plasma Gal-3 is associated with progression of kidney dysfunction in patients with T2DM independently of patient characteristics, including baseline kidney function. Moreover, Gal-3 identified an increasing gradient of absolute benefit of dapagliflozin for reducing kidney disease progression.
Abstract 4114417: Polygenic Risk in Heart Failure – Evaluating the Ability of a Polygenic Risk Score to Identify Risk of Future Heart Failure Events in 60,000 Patients from 6 TIMI Randomized Trials
Authors: Haller Paul , Melloni Giorgio , Berg David , Kamanu Frederick , Lai Yi-Pin , Antman Elliott , Bhatt Deepak , Bonaca Marc , Cannon Christopher , Giugliano Robert , O'Donoghue Michelle , Scirica Benjamin , Wiviott Stephen , Braunwald Eugene , Morrow David , Ellinor Patrick , Sabatine Marc , Ruff Christian , Marston Nicholas
Published: November 2024

Background:
The ability of polygenic risk scores (PRS) to predict heart failure (HF) beyond classic risk factors is unclear.

Aims:
To evaluate the risk of a HF PRS with incident hospitalization for HF (HHF) in patients with established cardiovascular disease.

Methods:
We analyzed a 59 SNP HF PRS (HERMES collaboration, Henry et al) in genotyped patients from six multinational TIMI randomized controlled trials (DECLARE, ENGAGE AF, FOURIER, PEGASUS, SAVOR, SOLID). Patients were stratified to low (quintile, Q1), intermediate (Q2-Q4), or high (Q5) genetic risk. We investigated the association of the HF PRS with incident HHF (median of 2.5 years) i) stratified by prior HF, and ii) across NTproBNP concentrations at baseline, using Cox-proportional hazard models. Results are reported as HR [95% CI], per 1-SD or with Q1 as a reference, and adjusted for ancestry (principal components 1-5), age, sex, trial, BMI, smoking, systolic BP, prior CAD, DM, AF, and eGFR.

Results:
In 59,906 pts (median age 66 years; 71% male; 26% prior HF), the HF PRS was associated with incident HHF (HR
adj
per 1-SD 1.08 [1.03, 1.13], p<0.001). Compared to low genetic risk pts, the HR
adj
for HHF was 1.12 [1.00, 1.26] in intermediate and 1.17 [1.02, 1.35] in high-risk pts. There were significant interactions between the HF PRS and prior HF (P
int
0.001), and NTproBNP (P
int
0.038), respectively. In pts without prior HF
(Fig A),
compared to low-risk pts, the risk was increased in high- (HR
adj
1.56 [1.25, 1.94], p<0.001) and intermediate-risk pts (HR
adj
1.27 [1.05, 1.54], p=0.013). In contrast, there was no significant association in pts with known HF at baseline (
Fig B
). Similarly, the HF PRS was significantly associated with HHF in pts with low but not elevated NTproBNP at baseline (
Fig C
).

Conclusion:
Our study confirms the role of polygenic risk for HF and demonstrates that a 59 SNP PRS can identify pts at increased risk of future HF events beyond traditional clinical factors, specifically in patients without established HF or elevated NTproBNP. These findings suggest a potential application of a HF PRS for screening and early identification of pts at increased risk for HF.
Abstract 4114597: Spontaneous coronary artery dissection: Case series and review of associated cardiovascular risks
Authors: Ahmed Eyad , Kaur Rajwant , Prakash Atul
Published: November 2024

Background:
Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of ACS, myocardial infarction, and sudden death particularly among young women and individuals with few conventional atherosclerotic risk factors. We reveiwed possible risk factors that could predispose to SCAD.

Methods:
We reviewed 13 consecutive patients presenting with SCAD across three different institutions over a period of 5 yrs and determined risk fatcors associated with this disase entity.

Results:
13 patients presented with SCAD represented % 0.5 of the total number of patients who underwent cardiac cathaterizations for chest pain requiring admissions. 11/13 (84%) were female. 5/13 (38%) were Caucasian or Hispanic, and 3/13 (23%) were African-American. Mean age age was 49.3 + years. 8/13 (61%) had associated hyperlipidemia with LDL levels > than 110 mg/dL, 9/13 (64%) had an A1c < 5.6% and only 1/13 (0.07%) had A1c of 6.4%. HTN was present in 6/13 (46%) of patients, and family history of SCD or heart disease were only seen in 2/13 (15%). None of the patients had features suggestive of associated fibromuscular dysplasia or connecive tissue disease. D-dimer was elevated in 5/13 (38%) with average value of 1578 ng/dL. Inflammatory markers were reviewed, only 3 patient has had ESR and CRP ordered, and only 1/3 had a mildly elevated CRP 3.9 mg/dL. Only 1/13 (0.07%) required intervention which was due to further drop in her ejection fraction requiring PCI, with improvement in her symptoms. All patients were treated with dual anti-platelet therapy for 1 year, 1 was discontinued due to persitent chest pain and decision was made to treat with only aspirin. Traditionally, risks for SCAD were thought to be due to non-atheresclerotic factors, however our case series shows that more then 60% of patients had elevated LDL's and 46% with hypertension, implying that traditional atheresclerotic risk factors should not be ignored and may play a crucial role. Autoimmune diseases were not found in any of our patients.

Conclusion and implications:
In this series patients who had SCAD had conventional risk factors of CAD including HLD and hypertension. The variability of co morbidities makes the identification of specific risk factors very difficult and none of the patients had Fibromuscular dysplasia or any signs of inflammation. Elevated D Dimer was also seen in a majority of patients, and all but one was managed medically with a favorable outcome
Abstract 4114970: Comparing efficacy and safety between pulsed field ablation, cryoballoon ablation and high-power short duration radiofrequency ablation in atrial fibrillation: A systematic review and Network meta-analysis.
Authors: Deepan Natee , Sripusanapan Adivitch , Prasitlumkum Narut , Siranart Noppachai , Chokesuwattanaskul Ronpichai , Navaravong Leenhapong , Kewcharoen Jakrin , Pajareya Patavee , Tokavanich Nithi
Published: November 2024

Background:
Pulsed field ablation (PFA) and high-power short-duration radiofrequency ablation (HPSD) are emerging techniques for treating atrial fibrillation (AF), offering promising results compared to cryoballoon ablation (CBA). This network meta-analysis aims to evaluates the efficacy and safety of PFA, HPSD, and CBA.

Method:
PubMed, Embase, Cochrane Central Register of Controlled Trials, and EBSCO Information Services were systematically searched for relevant studies until April 2024. The primary outcome is freedom from atrial arrhythmia. A random-effects model was used for data synthesis, and P-scores were employed for outcome ranking. Point estimation (odd ratios) was calculated for comparisons.

Results:
Fifteen studies were included in our network meta-analysis, involving 5,093 atrial fibrillation patients: 812 (16%), 2,659 (52%), and 1,622 (32%) patients underwent PFA, CBA, and HPSD, respectively. PFA demonstrated the highest efficacy (P-scores 99.3%). Point estimation between PFA and HPSD, and PFA and CBA, were 1.394 (95% CI: 1.047-1.858) and 1.479 (95% CI: 1.134–1.929), respectively. PFA had higher complications compared to HPSD (OR=4.44, 95% CI: 1.405-14.031) and CBA (OR=2.581, 95% CI: 0.992–6.720). HPSD had the shortest fluoroscopic time (P-scores 100%), while CBA had the longest (P-scores 0%). PFA had the shortest procedural time compared to CBA and HPSD with P-scores of 100% 50% and 0%, respectively.

Conclusion:
PFA showed higher efficacy but higher complication risk than HPSD and CBA. HPSD and CBA demonstrated similar efficacy and safety.
Abstract 4115531: Relationship between Ventricular Workload and Functional Response to Balloon Pulmonary Angioplasty (BPA) Therapy for Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Authors: Nashed Nicole , Ang Lawrence , Fregoso Alma , Omens Jonathan , Buchalla Taylor , Chavez Paul , Poch David , YANG JENNY , Kim Hyong , Mahmud Ehtisham
Published: November 2024

Background:
WHO functional classification (FC) is used to evaluate clinical response to BPA therapy and is associated with hemodynamic improvements in CTEPH patients. The relationships between FC and specific metrics of left and right ventricular workload during BPA remain unclear.

Methods:
CTEPH patients who underwent at least six BPA sessions and were included in the UCSD BPA registry were included for analysis. Left ventricular (LV) and right ventricular (RV) cardiac power output (CPO) and stroke work index (SWI) using thermodilution cardiac output were measured, along with FC, during each BPA session. BPA “responders” showed improved FC from III/IV at baseline to I/II after BPA therapy. BPA “non-responders” had unchanged FC III/IV symptoms before and after BPA therapy. ANOVA and Student T tests were used and P-value <0.05 was significant.

Results:
A total of 66 subjects (55.5% female, BMI 28.3±6.10kg/m
2
,16.7% prior pulmonary thromboendarterectomy surgery) were enrolled. Greater subject functionality by FC was significantly associated with higher LVCPO (class IV to I: 0.88±0.15, 0.94±0.28, 1.08±0.31, 0.95±0.27 watt; p<0.001), higher LVSWI (29.4±6.6, 35.6±9.4, 40.8±8.8, 43.4±11.1 g*m/beat/m
2
; p<0.001), and lower RVCPO (0.37±0.10, 0.34±0.12, 0.34±0.14, 0.24±0.09 watt; p=0.003). RVSWI was not significantly associated with FC (14.8±3.7, 15.4±5.1, 15.1±5.0, 12.5±3.3 g*m/beat/m
2
; p=0.075). Likewise, higher mean LVCPO (1.1±0.30 vs 0.93±0.27 watt; p<0.001) and LVSWI (41.1±9.1 vs 35.2±9.4 g*m/beat/m
2
; p<0.001), but not RVCPO or RVSWI, were observed in subjects with FC I/II versus FC III/IV symptoms. BPA responders versus non-responders had higher overall LVCPO (1.01±0.27 vs 0.89±0.27 watt; p<0.001) and LVSWI (39.0±8.9 vs 33.2±8.4 g*m/beat/m
2
; p<0.001), but not RVCPO (0.33±0.13 vs 0.34±0.13 watt; p=0.465) or RVSWI (15.2±4.8 vs 14.9±5.1 g*m/beat/m
2
; p=0.694). Responders also had higher baseline LVSWI (p=0.029) and post-BPA LVSWI (p=0.028) compared to non-responders.

Conclusions:
CTEPH patient functionality and symptoms during BPA therapy are associated with metrics of left and right ventricular workload. Patients with more severe FC III/IV symptoms produce lower LV workload. Treatment responders with improved FC after BPA therapy achieve higher overall, pre-BPA, and post-BPA LV workload. Specific metrics of ventricular workload may be helpful determinants of CTEPH patient symptoms and BPA treatment response.
Abstract 4115652: Effect of the sodium-glucose co-transporter 2 inhibitor, Dapagliflozin, on ventricular repolarization electrocardiographic parameters: DAPA-ECG study
Authors: Campos Rodrigo , MOREIRA DALMO , Fonseca Gabriel
Published: November 2024

Background:
In patients with type 2 diabetes (T2D), hyperglycemia and glycemic variability lead to prolongation and greater heterogeneity of ventricular repolarization, manifested on the electrocardiogram through an increase in QT, QTc, TpeakTend (TpTe) intervals and the TpTe/QT ratio, increasing the risk of potentially malignant arrhythmias. Dapagliflozin has demonstrated efficacy in reducing cardiovascular events in T2D patients and in the risk of serious ventricular arrhythmias and sudden cardiac death. However, the exact mechanisms by which dapagliflozin confers this protection have not yet been fully elucidated.

Goals/Aims:
The main objective of the study was to evaluate the impact of dapagliflozin on the TpTe interval of patients with T2D, and secondarily, it examined its impact on various electrocardiographic parameters such as the QT and QTc intervals, the TpTf/QT ratio, QT dispersion, J-T peak interval, QRS-T angle and heart rate.

Methods:
This randomized, prospective, multicenter and open-label study involved 174 patients with T2D, divided into two groups: one treated with dapagliflozin and the other with optimized medical therapy without iSGLT2. Clinical, electrocardiographic, laboratory and echocardiographic evaluations were carried out at the beginning and after three months. The statistical analysis included means, standard deviations, quartiles, and frequencies, with 95% confidence intervals, using Chi-square (or Fisher) and t-test (or Mann-Whitney) for initial differences, and a linear mixed-effects model to evaluate the results, adopting a significance level of 0.05.

Results:
The TpTe interval was significantly reduced in the dapagliflozin group from 76.87 ± 12.47 to 67.80 ± 10.34 (p<0.001), and the QTc interval reduced from 424.07 ± 30.76 to 411.26 ± 25.31 (p=0.022). The TpTe/QT ratio in the dapagliflozin group was shortened from 0.20 ± 0.03 to 0.18 ± 0.02 (p<0.001). Both groups showed reductions in mean blood glucose and HbA1c, with a greater decrease observed in the control group. No significant changes were recorded in other variables analyzed.

Conclusion:
In patients with T2D, dapagliflozin significantly reduced the duration of the TpTe and QTc intervals, in addition to the TpTe/QT ratio. These findings indicate a decrease in ventricular electrical remodeling with a potential cardioprotective effect of dapagliflozin, which would partly explain its benefits in reducing potentially malignant ventricular arrhythmias and sudden cardiac death.
Abstract 4115684: Outcomes Associated with Remote Monitoring without In-person Evaluations for Patients with Cardiovascular Implantable Electronic Devices
Authors: Derry Laura , Whooley Mary , Raitt Merritt , Rotering Thomas , Shen Hui , Tarasovsky Gary , Dhruva Sanket
Published: November 2024

Introduction:
Traditionally, patients with cardiovascular implantable electronic devices (CIEDs: pacemakers and implantable cardioverter-defibrillators) attend in-person visits at least annually, paired with remote monitoring (RM). Because similar data are obtained through RM and in-person visits, it is unclear whether routine in-person visits are necessary. Two small trials conducted outside the U.S. found no difference in clinical outcomes without routine in-person visits for patients engaged in RM, but their generalizability is uncertain.

Research Aim:
To determine whether routine visits for CIED care are associated with major adverse cardiac events (MACE) among patients in the U.S.’ largest public integrated health system, the Veterans Health Administration (VHA).

Methods:
We classified Veterans who received their CIED care within VHA and sent ≥1 RM transmission between 7/1/20-6/30/21 into one of three groups based on type of clinical encounters for CIED care: (1) any in-person, (2) virtual-only (telephone and/or videoconference), or (3) no in-person or virtual visits. Data were obtained from the VHA National Cardiac Device Surveillance Program and Corporate Data Warehouse. The primary outcome was MACE, a composite of all-cause mortality, stroke, and cardiac hospitalization, between 7/1/21-6/30/22. We performed multivariable logistic regression, adjusting for patient and device characteristics.

Results:
Of 40,366 patients, 27,298 (68%) had at least one in-person visit, 9,268 (23%) had only virtual visits, and 3,800 (9%) had neither. Mean age was 73 years, 97% were male, and 37% lived in rural areas. There were 6522 (23.9%) MACE events among patients who had in-person visits, 2116 (22.8%) among those who had only virtual visits, and 947 (24.9%) among those who had no visits. After multivariable adjustment, there was no significant association between encounter type and MACE [odds ratio 0.93 (95% CI: 0.85-1.01) for patients who had any in-person or virtual visits compared to those without].

Conclusion:
Among patients engaged in RM, the odds of MACE was similar regardless of whether patients had in-person or virtual visits versus no visits. Although there could be unmeasured confounding, these results suggest routine in-person or virtual visits may no longer be necessary for CIED care with RM. Patients, clinicians, and healthcare systems could benefit by reducing low-value visits and re-focusing resources on visits that yield actionable interventions.
Abstract 4115690: COL4A1-related Vascular Disease Displays Strikingly Different Penetrance, Onset, and Expressivity in Literature versus Biobank-Derived Cases
Authors: Blair David , Penon-Portmann Monica
Published: November 2024

Monogenic cardiovascular diseases present throughout the human lifespan with varying symptoms. For most, our understanding of their penetrance, onset, and expressivity is derived from published case reports. The extent to which these literature-derived cases capture the full allelic and phenotypic spectrum is unknown, particularly since the literature is biased towards severe presentations. To illustrate, we investigated the penetrance (i.e. the presence of at least one symptom), onset, and phenotypic expressivity of a rare genetic disease linked to hemorrhagic stroke and other complications:
COL4A1
-related vascular disease (COL4A1VD, or Gould Syndrome). We performed a systematic review of COL4A1VD cases reported in the biomedical literature (
N
=459), normalizing their genetic variants and symptoms to controlled terminologies. We then investigated the phenotypic expression among COL4A1VD pathogenic variant carriers isolated from two population-scale biobanks (the UK Biobank and All of Us Research Program; combined
N
=714,246), identifying 178 subjects (prevalence: 0.025%) that should be at high risk for COL4A1VD-related symptoms. Based on the literature, the penetrance of COL4A1VD is approximately 92% (95% CI: 90%-95%), with each case expressing 4.3 symptoms on average. Neurologic complications were the most common finding, observed in 85% of symptomatic patients. Alternatively, the biobank-derived cohort displayed an overall enrichment for disease-related symptoms
(COL4A1
pathogenic carriers are more likely to have increased symptom burden compared to non-carrier controls; P<0.005), but the penetrance of the variants was substantially reduced (34%; 95% CI: 26%-41%). In addition, this cohort expressed fewer symptoms on average (0.8 per carrier), with renal complications being far more common (78% of symptomatic biobank patients vs 22% of literature-derived cases;
P
< 0.001). Finally, the apparent age-of-onset was much later for the biobank-derived cohort (57-years vs 5-years for the literature cases). Most of these differences reflect the distinct ascertainment of these two COL4A1VD cohorts, but they also highlight our incomplete understanding of the true penetrance, expressivity, and onset for this rare disease. These results have important implications for COL4A1VD-related genetic counseling and surveillance, and they highlight a need for new methods that formally integrate the rare disease knowledge captured from these distinct data sources.
Abstract 4115832: Statin Intolerance due to Muscle Symptoms Affects Management of Patients: Insights from the CLEAR Outcomes Trial
Authors: Laufs Ulrich , Lincoff Abraham , Nicholls Stephen , Li Na , Sasiela William , Bloedon Leanne , Robinson Paula , Nissen Steven , Thompson Paul
Published: November 2024

Background:
In CLEAR Outcomes the non-statin bempedoic acid (BA) 180 mg daily reduced MACE-4 (nonfatal MI, nonfatal stroke, coronary revascularization, or CV death) by 13% in 13970 patients at high CV risk with statin intolerance (SI) over a median of 40.6 months. This is the largest prospective database of patients with SI.

Aims:
To assess whether there were differences in SI symptom history and whether this influenced the clinical course during CLEAR Outcomes.

Methods:
SI symptoms and impact on activities of daily living (ADL) were recorded prior to randomization. Patients were grouped post hoc as reporting only statin associated muscle symptoms (SAMS), only non-muscle adverse effects (NonSAMS), or BOTH.

Results:
At baseline 6887 (49.3%) patients reported SAMS, 2485 (18%) NonSAMS, and 4587 (33%) BOTH.

SI symptoms had a moderate/severe impact on ADL in 62% SAMS, 48% NonSAMS, and 69% BOTH. Use of any lipid modifying treatment at baseline was 43% SAMS, 36% NonSAMS, and 42% BOTH. Compared to placebo, BA reduced LDL-C at 6 months by 21% in SAMS, 22% in NonSAMS, and 21% in BOTH. There was no difference in the effect on MACE-4 by SI group. New use of moderate/high intensity statin during the study was relatively infrequent (3.2-8.0%) but higher in PBO than BA in all SI groups and was not generally maintained at study end (Table 1). Muscle adverse events (AE) were more frequent and resulted in higher rates of treatment DC in SAMS/BOTH vs NonSAMS (Table 2). There was no difference between BA and PBO in the rate of muscle related AE.

Conclusion:
SAMS are the predominant cause of SI in patients in CLEAR Outcomes. Patients with a history of SAMS had higher rates of muscle AE and study drug DC due to muscle AE versus NonSAMS. Muscle AE rates and study drug DC were balanced between BA and PBO within each SI symptom subgroup. CLEAR Outcomes exhibits the challenges of treating patients with SI. These data also demonstrate that BA can be useful in reducing CV risk in this patient population.
Abstract 4116141: Von Willebrand Factor Inhibition by BB-031 Prevents and Thrombolyses Clots in a Murine Model of Venous Thrombosis
Authors: Carfora Arianna , Franceschelli Dominic , Patel Mayur , Wheeler Debra , Covarrubias Roman , Bermeo-Blanco Oscar , Gumina Richard , Nimjee Shahid
Published: November 2024

Introduction:
Venous thromboembolism (VTE) manifesting as deep vein thrombosis and pulmonary embolus results in ~300,000 US deaths annually. Risk factors include obesity and current therapy limitations leave ~ 50% of patients with no effective treatment. Circulating von Willebrand Factor (VWF) levels portend poor clinical outcomes. BB-031, an aptamer-based VWF inhibitor with prophylactic and arterial thrombolytic efficacy may translate to VTE.

Methods:
Jugular vein occlusion (JVO) was induced by FeCl
3
either before or after intravenous treatment in 14 week old male and female C57/BL6 wild type (WT) or male diet-induced obese (DIO) mice. 5.0 mg/kg BB-031 was administered as a bolus, 10.0 mg/kg rtPA with 10% bolus and remaining 90% over 60 minutes, 400 U heparin as a bolus, or vehicle. Doppler jugular vein flow velocity was recorded from baseline to determine patency 30 minutes after injury. Thrombolytic clots were stabilized for 20 minutes.

Results:
Prophylactic mice occluded ~20 minutes after FeCl
3
application with rtPA=18.32 +/- 6.54 min, heparin 17.14 +/- 8.53 min, and vehicle 17.29 +/- 7.26 min. Thrombosis did not occur with BB-031 treatment (n=4-12/group). Treatment
after
JVO resulted in no difference compared to vehicle in male WT mice, but BB-031-treated WT females resulted in 76.09% recanalization 35 minutes after occlusion compared to rtPA (9.64%, p<0.0001), heparin (30.95%, p=0.7306), or vehicle (22.07%, p<0.0001), (n=5/group).
Male
DIO mice significantly reperfused with BB-031 (100%) vs rtPA (10.52%), heparin (4.54%), and vehicle (22.50%), p<0.0001, (n=4-6/group).

Conclusion:
VWF inhibition by BB-031 maintains patency in a VTE murine model offering future therapeutic alternatives.