bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4139249: Cost or Benefit? Analysis of a Virtual Health Coaching Intervention for Caregivers of Patients with Heart Failure
Authors: Sun Chuxuan , Hirschman Karen , Matus Austin , Stawnychy Michael , Goba Miatta , Thomas Gladys , Ashare Rebecca , Gordon Deborah , Bowles Kathy , Riegel Barbara , Coe Norma
Published: November 2024

Background:
Despite the large role of informal caregivers in heart failure (HF) care, the cost-effectiveness of interventions supporting informal caregivers of patients with HF is unclear.

Aim:
Compare the cost-effectiveness of a virtual health coaching intervention ("ViCCY,” Virtual Caregiver Coach for You) designed to improve self-care vs. health information alone for informal caregivers of patients with HF.

Methods:
In this randomized controlled trial, 250 informal caregivers were randomized in a 1:1 ratio to receive a combination of ViCCY and health information or health information only for 6 months. Caregiver healthcare utilization (i.e., hospitalization, emergency visits, ambulance use, diagnostic/therapeutic procedures, and home care) was self-reported at 1, 3, 6, 9, and 12 months after randomization. Incremental cost-effectiveness ratio (ICER) was calculated as incremental costs per quality-adjusted life-year (QALY) within the 12-month trial period. Both unadjusted and adjusted regression analyses were used to measure healthcare utilization and cost. Primary analyses were conducted on the 164 caregivers with complete data on both QALY and healthcare costs. Sensitivity analyses were conducted on samples with complete data for either QALY or healthcare costs. Calculations were made to estimate the ICER for a hypothetical scaled version of the intervention, with 12 health coaches serving 336 informal caregivers per year, including training and fidelity costs.

Results:
The intervention improved QALYs by 0.036 at a cost of $862.4 per caregiver for an ICER of $23,956 for the ViCCY group (Table). The overall effect of the ViCCY intervention was a reduction of $1,114.8 in healthcare spending, which was mainly driven by lower utilization and costs associated with hospitalization. The results were robust to sensitivity analyses. Scaling the intervention could lead to even greater gains.

Conclusions:
At a conservative threshold of US$50,000/QALYS, these findings indicate that ViCCY can be a cost-effective and affordable way of enhancing the self-care of informal caregivers of patients with HF while simultaneously reducing caregiver healthcare costs, particularly the costs associated with caregiver hospitalization.
Abstract 4139258: Aspirin vs Clopidogrel as a Monotherapy secondary prevention in Patients with Coronary Artery Disease: An updated Meta-Analysis
Authors: Almaadawy Omar , Elnady Mohamed , Almahdy Mohamed Ahmed , Elshimy Abdelrahman , Sarhan Menna , Hassan Abdul Rhman , Moheyeldin Eman , Mohamed Alshaimaa , Ali Nada , georges claudia , Elsalmouny Youmna , Al-Azizi Karim
Published: November 2024

Introduction:
Antiplatelet therapy plays a significant role in the management of patients with coronary artery disease (CAD) to prevent cardiovascular events. Current guidelines recommend 6-12 months of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) followed by either aspirin or clopidogrel monotherapy indefinitely. Previous meta-analyses have suggested a potential superiority of clopidogrel over aspirin. However, given the evolving landscape of cardiovascular medicine, there is a need for updated evidence to inform clinical practice.

Hypothesis:
This systematic review and meta-analysis, to our knowledge the most up-to-date, aims to compare the effectiveness and safety of aspirin versus clopidogrel as monotherapy in patients with coronary artery disease (CAD).

Methods:
We searched PubMed, Embase, and Cochrane Library databases for relevant randomized controlled trials (RCTs) and Non (RCTs) Studies published up to April 2024. The primary outcomes were Major Adverse Cardiovascular and Cerebrovascular Events, myocardial infarction, stroke, and Death, while secondary outcomes included major bleeding events, target vessel revascularization, repeated revascularization, and stent thrombosis. heterogeneity analysis, and pooled analysis conducted by RevMan 5.3 software.

Results:
A total of eleven (11) studies involving 26324 patients, of whom 11435 (43.4%) received clopidogrel met the inclusion criteria. Mean follow-up was 12-36 months. Duration of DAPT before antiplatelet monotherapy was 1-18 months. The meta-analysis revealed a significant reduction with Clopidogrel monotherapy in all the following compared to Aspirin monotherapy; myocardial infarction [ 0.77 -95%CI -(0.64 - 0.93)], stroke [ 0.59 -95%CI- (0.48 - 0.74)], major bleeding events [ 0.66 -95%CI- (0.53 - 0.84)], and repeated revascularization [ 0.88 - 95% CI ( 0.77 - 0.99 )]. There was no significant difference in the risk of major adverse cardiovascular and cerebrovascular events, death and cardiac death.

Conclusion:
Clopidogrel monotherapy may be associated with a lower risk of major bleeding, MI, stroke and repeated revascularization compared to aspirin monotherapy in patients with CAD. This supports the use of clopidogrel over aspirin in patients with CAD who require secondary prevention with long-term antiplatelet monotherapy.
Abstract 4139264: Outcomes Of Pulmonary Vein Isolation With Or Without Adjunctive Posterior Wall Isolation In Patients With Paroxysmal Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Ahmed Usman , Kamran Farooq , Ahmed Shahzaib , Ashraf Danish Ali , Bilal Muhammad Ibraiz , Amin Zubair , Ahmad Eeman
Published: November 2024

Introduction:
Pulmonary vein isolation (PVI) is a catheter ablation (CA) technique employed as a treatment strategy for atrial fibrillation in young patients or those who do not respond to medical therapy. Techniques for PVI include radiofrequency (RFA) ablation and balloon cryoablation. The left atrial posterior wall has been recognized as a significant anatomical area involved in the onset and persistence of atrial fibrillation (AF). However, the impact of additional posterior wall isolation (PWI) during PVI remains uncertain.

Research Question:
What are the outcomes of pulmonary vein isolation compared to pulmonary vein isolation with adjunctive posterior wall isolation in patients with paroxysmal atrial fibrillation?

Goals:
To determine the efficacy of adjunctive posterior wall isolation in treating persistent AF.

Methods:
A systematic literature search was conducted on various databases (Pubmed/Medline, EMBASE, Google Scholar, Scopus) from inception until March 2024, to include studies comparing outcomes of patients undergoing management of paroxysmal AF with either PVI + concurrent PWI versus only PVI. Observational studies and Randomized Controlled Trials were included. Review Manager (v 5.3) was used for pooled analysis of included studies employing risk ratio (RR) as the effect measure (4).

Results:
We conducted a random-effects meta-analysis, pooling data from 5 studies with a total of 2,441 patients. Our analysis revealed a significant improvement in AF recurrence for the cryoablation technique with PVI+PWI (RR=0.56, 95% CI: 0.41, 0.76, I2=0%, p=0.0002) but no significant result was found for PVI+PWI in RFA (RR=1.37, 95% CI: 0.87, 2.18, I2=0%, p=0.18) for AF. For the recurrence of all arrhythmias, the risk ratios for cryoablation and RFA are 0.60 (95% CI: 0.46, 0.78, I2=0%, p=0.0001) and 1.17 (95% CI: 0.83, 1.65, I2=0%, p=0.37) respectively, significant in the case of cryoablation and non-significant for RFA.

Conclusion:
Concurrent PWI with PVI with the cryoablation technique in patients for the management of paroxysmal AF reduces the risk of recurrent AF. Due to the limited number of studies included, it is possible that the results were underpowered. Further prospective studies in the future are warranted.
Abstract 4139307: Machine Learning Identifies Predictors of Poor Outcomes in Patients with Heart Failure Presenting to the Emergency Department for Chest Pain
Authors: Kraevsky-Phillips Karina , Ji Rui Qi , Thangavel Sarumathi , Al-Zaiti Salah
Published: November 2024

Introduction:
Heart failure (HF) is associated with unique comorbidities and sequelae, which can affect clinical presentation and patient outcomes. This is specifically challenging when patients are evaluated for suspected acute coronary syndrome (ACS). We sought to compare the most important predictors of poor outcomes in patients with and without HF seen in the emergency department (ED) for ACS.

Methods:
This was a secondary analysis of a prospective observational cohort study of consecutive patients seen for symptoms suggestive of ACS, such as chest pain (CP) and dyspnea, in the EDs of three UPMC-affiliated tertiary care hospitals (NCT04237688, clinicaltrials.gov). Primary outcome was 30-day major adverse cardiac events (MACE), adjudicated by two independent reviewers. Clinical data were collected form charts and we used KNN to impute missing data for features, most of which had less than 12.5% missingness. For features with greater than 12.5% missingness (i.e., BNP, Mg), binary indicators were added to flag missing values. Data were normalized using the Euclidean norm. Two random forest (RF) classifiers were trained using 10-fold cross validation with 71 manually selected features available early in the ED course (i.e., vital signs, labs, past medical history, ECG), and tested on patients with and without known HF. Model performance was evaluated using AUROC, and top features were identified with SHAP values.

Results:
The sample included 2400 patients (age 59 ± 16 years; 47% female, 41% Black, 15.9% ACS), of whom 438 had HF (age 66 ± 14 years; 45% female, 49% Black, 15.1% ACS). Individuals with HF were more likely to experience MACE (38% vs 23%,
p
<.001). The model had higher classification performance in patients without HF (AUC 0.89 vs 0.70). Figure 1 shows top MACE predictors for patients with and without HF.

Conclusion:
The RF model performed sub-optimally among patients with HF, who were more likely to have poor outcomes moderated by characteristics such as low pulse oximetry, BNP measurement, and anemia, which are related to pathophysiology of HF. Current routine ED assessment tools for CP (i.e., HEART score) do not translate well to patients with HF, which requires more elaborate diagnostic testing.
Abstract 4139311: Comparative Effects of Education and Income Levels and Cardiovascular Risk Factors for the Risk of Ischemic Heart Disease, Ischemic Stroke, or Peripheral Artery Disease Associated Mortality
Authors: Fueller David , Liu Chang , Boten David , Ritter Oliver , Doerr Gesine , Jain Vardhmaan , Desai Shivang , Sperling Laurence , Sun Yan , Quyyumi Arshed
Published: November 2024

Background:
Low educational attainment and income are associated with a higher risk of adverse cardiovascular (cv) outcomes.

Research Question:
The impact of lower education and income levels on the risk of cv death defined as ischemic heart disease, ischemic stroke, or peripheral artery disease associated mortality, and how this compares to traditional cv risk factors including overweight/obesity, hypertension, type 2 diabetes, smoking history, frequent alcohol consumption, physical activity, and family history for heart disease.

Methods:
In this prospective study involving 396,614 participants of the United Kingdom Biobank (UKB) with no history of ischemic heart disease, ischemic stroke, or peripheral artery disease at enrollment, we divided participants into five groups according to annual household income as defined in UKB, and six groups of educational attainment created using the International Standard Classification of Education. Five BMI (kg/m
2
) categories were created (<25; 25-29.9; 30-34.9; 35-39.9, ≥40). The association of education and income with cv death was assessed using Fine-Gray sub-distribution hazard models including covariate adjustment for age, sex, race, number of people in the household, spatial socioeconomic deprivation, plasma lipids, and traditional cv risk factors.

Results:
Mean age was 55.8 years, 46% were men, and mean time of follow-up was 14.3 years. There were 3,930 cv deaths. One level lower in income was associated with a higher risk for cv death (aHR 1.28, 95% CI 1.22-1.34, p <0.0001). One level lower in education was non-significantly associated with cv death (aHR 1.02, 95% CI 1.00-1.04, p=0.06). One level lower in income was associated with a higher risk for cv death compared to one group higher in BMI categories (aHR 1.15, 95% CI 1.10-1.21, p <0.0001) and was comparable to the risk associated with having a father, mother, or sibling with heart disease.

Conclusion:
The risk for cv death associated with one level lower in income as assessed in the UKB is higher than the risk associated with one group higher in BMI categories and comparable with a family history for heart disease, highlighting the importance to assess socioeconomic factors in cardiovascular risk assessments.
Abstract 4139315: From Mutation to Dysfunction: The Effect of Na
V
1.5 Selectivity Filter in Arrhythmia Pathogenesis
Authors: Selimi Zoja , Tarasov Mikhail , Meng Xiaolei , Dias Patricia , Moise Bianca , Veeraraghavan Rengasayee , Radwanski Przemyslaw
Published: November 2024

Background:
Mutations in the SCN5A gene, encoding the cardiac voltage-gates sodium channels (Na
v
1.5) are associated with life threatening arrhythmias. Recently a missense mutation in the selectivity filter, SCN5A-K1419E, has been identified in patients with Brugada syndrome and has also been linked to long QT. Prior studies demonstrated that SCN5A-K1419E substitution alters ion selectivity of Na
V
1.5, conferring Ca
2+
permeability, and thereby lowering overall conductance. However, the arrhythmogenic mechanism of selectivity filter mutations have not been established.

Methods and results:
To address this, we generated heterozygous Scn5a-K1421E mice (homolog of human SCN5A-K1419E). Cardiomyocytes from these mice exhibited reduced peak Na
+
current (I
Na
) density with a reversal potential consistent with altered permeability to other ions relative to wild type (WT). Importantly, Na
V
1.5 expression in Scn5a-K1421E hearts was unchanged compared to WT as revealed by confocal immunolabeling studies. Consistent with reduced I
Na
density in Scn5a-K1421E, conduction velocity (CV) slowing was observed in optical mapping experiments. Notably, flecainide (1µM) challenge profoundly slowed CV in Scn5a-K1421E relative to WT hearts, resulting in ventricular tachyarrhythmias (VT)
in vivo
. Intriguingly, despite reduction in peak I
Na,
Scn5a-K1421E cardiomyocytes exhibited enhanced late Na
+
influx relative to WT, which translated to prolonged QT interval
in vivo
.

Conclusion:
Overall, Scn5a-K1421E mice exhibit an overlap phenotype consistent with Brugada and long QT type 3 syndromes revealing complex effects of K1421E on Na
V
1.5 function.
Abstract 4139317: Epidemiologic and genetic associations between proteomic markers and thoracic aortic diameter
Authors: Wells Alexander , Brundage James , Zamirpour Siavash , Pirruccello James
Published: November 2024

Introduction:
Enlargement of the thoracic aorta is clinically silent but predisposes to the highly morbid medical conditions of aortic dissection and rupture. Evidence suggests that clinical and genetic factors play a role in the pathogenesis of aneurysm. Here, we extend these efforts by identifying circulating proteomic markers linked to aortic diameter.

Research Question:
We investigate whether circulating protein levels correlate with aortic diameter

Goals:
1. Identify proteins whose circulating levels correlated with aortic diameter

2. Investigate whether protein levels may causally influence aortic diameter using Mendelian randomization

Methods:
A total of 7,099 UK biobank participants had both ascending aortic diameter measured from MRI and 2,920 circulating proteomic markers measured with the Olink Explore 3072 panel. For each protein, a linear regression model was trained to estimate ascending aortic diameter, adjusted for age at time of MRI, time between Olink panel and MRI, and sex. A genome-wide association study (GWAS) of ascending aortic diameter was conducted after excluding participants related within 3 degrees of kinship to those with proteomic measurements, producing summary statistics for two-sample Mendelian randomization (2SMR). We used independent cis-protein quantitative trait loci (within 1 megabase of the gene) as the exposure and the ascending aortic diameter summary statistics as the outcome in a 2SMR framework.

Results:
Circulating levels of 185 proteins were associated with ascending aortic diameter. Using 2SMR, we observed evidence consistent with a causal role for 43 proteins. Three proteins were significant in both analyses: CCN3 (a suppressor of vascular smooth muscle proliferation); BMP6 (a member of the TGF-beta superfamily); and RGMA (depleted in aortic plaques). Both analyses found a direct relationship between CCN3 levels and aortic diameter and an inverse relationship between BMP6 levels and aortic diameter. The 2SMR found a direct relationship between RGMA levels and aortic diameter, whereas the regression model found an inverse relationship.

The greatest 2SMR effect estimate was between greater levels of circulating methionine sulfoxide reductase A (involved in repair of oxidative damage in vascular smooth muscle cell mitochondria) and reduced ascending aortic diameter.

Conclusions:
Circulating protein levels were associated with ascending aortic diameter, some of which may play causal roles in aneurysm development.
Abstract 4139340: Atherosclerotic Plaque Progresses Over Time in Healthy Individuals Without MACE, Risk Factors, or Interventions
Authors: Aldana Jairo , Kinninger April , Krishnan Srikanth , Ichikawa Keishi , Budoff Matthew , Karlsberg Ronald
Published: November 2024

Introduction:
Studies on the natural history of coronary artery disease have traditionally evaluated the progression of the disease in the presence of MACE, risk factors or risk modifying interventions including pharmacological and non-pharmacological treatment. It is not known how atherosclerotic plaque progresses over the time in the absence of MACE, risk factors or risk modifying interventions.

Aim:
To evaluate the natural history of atherosclerosis in healthy populations on serial CCTA.

Methods:
NATURE-CT retrospectively selected 205 participants from two sites in Los Angeles. Subjects underwent at least two CCTA scans, the initial scan showing CAC ≤100, absence of MACE, not placed on lipid modifying therapy in the first and last scan, and at least 2 years apart. Patients with diabetes, familial hypercholesterolemia or chronic kidney disease were excluded. FDA cleared automated software Cleerly Labs (Cleerly.Inc, NY, NY) quantified plaque and stenosis. Primary outcome will be the observed annualized rate of change in the atherosclerotic plaque during the observation period.

Results:
At baseline visit, the mean age of the cohort was 54.9±10.2 (years), 72% (147) being white males, 0% had DM, 0% had lipid modifying therapy, 24% (49) had hypertension, 28% (57) reported hyperlipidemia and 15% (30) were ever smokers. Mean LDL was 111.6±32.0 mg/dl and the average time between CCTA scans was 4.9±2.2 years. Over half (54%) of the cohort had a CAC=0 at the baseline visit. At baseline, total non-calcified plaque volume was (median and IQR in mm3) [27.5 (10.1, 55.5)] versus at follow-up [53.5 (24.0, 97.9)], with a calculated annualized median change of [4.9 (1.4, 9.6)] in non-calcified plaque. Total calcified plaque volume was [0.3 (0.0, 5.7)] and at follow-up [3.2 (0.1, 18.2)], with a calculated annualized median change of [0.4 (0.0, 2.4)] in calcified plaque. At baseline, 9% (19 subjects) had low attenuation plaque greater than zero, and at follow-up, 23% (48 subjects). 6 subjects had annual change in PAV>=1% (3%) and 23 subjects had annual change in PAV >=0.59% (11%).

Conclusions:
Atherosclerotic plaque in the absence of MACE, risk factors or risk modifying interventions progresses overtime. The burden of non-calcified plaque has greater progression than calcified plaque. In healthy subjects, the presence of low attenuation plaque is infrequent. When observed, its progression is present overtime. Rapid plaque progression is present in some healthy subjects.
Abstract 4139367: A major uremic toxin indoxyl sulfate impairs macrophage efferocytosis and accelerates atherogenesis: a potential mechanism for cardiovascular risk in chronic kidney disease
Authors: Jha Prabhash , Lupieri Adrien , Sonawane Abhijeet , Le Thanh-Dat , Becker-Greene Dakota , Chelvanambi Sarvesh , Turner Mandy , Nakamura Yuto , Passos Livia , Kasai Taku , Vromman Amelie , Holden Rachel , Libby Peter , Tabas Ira , Singh Sasha , Aikawa Elena , Aikawa Masanori
Published: November 2024

Background:
Chronic kidney disease (CKD) is a global burden with high unmet medical needs. Despite the availability of potent drugs such as statins, CKD patients have accelerated atherogenesis and succumb to vascular complications. Underlying mechanisms, however, remain unclear. Elevated levels of a major uremic toxin, indoxyl sulfate (IS), is an independent cardiovascular risk factor in CKD patients. Using a multi-layer systems approach followed by in vitro and in vivo experiments, we investigated the mechanisms by which IS accelerates atherogenesis.

Methods&Results:
Gene expression meta-analysis of microarray datasets of patients with atherosclerosis or CKD (CKD n=102; atherosclerosis n=136) implicated efferocytosis as a shared mechanism between two diseases (Fig. A and B). Impaired efferocytosis contributes to the development of high-risk atherosclerotic plaques.
In vitro
validation using live cell imaging demonstrated that clinically relevant concentration of IS (1mmol/L) suppressed efferocytosis of human primary macrophages (n=6 PBMC donors) (Fig. C). In
in vivo
experiments, daily IS administration (100 mg/kg/day, i.p.) for 4 weeks in hyperlipidemic Ldlr-/- mice caused expansion of %-necrotic core area (n=10/group, Fig. D), typical features of high-risk plaques. Multi-omic integration of global proteomics and transcriptomics of IS-treated human primary macrophages and Ldlr-/- mice atherosclerotic plaque further enriched efferocytosis-related signals and identified reduced growth arrest specific protein 6 (GAS6), a tethering molecule between macrophages and dying cells, as a potential key mediator. IS treatment decreased the expression levels of GAS6 in both human primary macrophages (n=14, Fig. E) and Ldlr-/- mice atherosclerotic plaque (n=6, Fig. F). Moreover, in vivo gain-of-function studies in macrophage-selective Gas6 knock-in mice demonstrated that Gas6 restored IS-induced defective efferocytosis in peritoneal macrophages (Fig. G and H).

Conclusions:
IS suppresses GAS6, impairs human macrophage efferocytosis, and accelerates experimental atherogenesis. Our findings provide molecular bases for the future development of new therapies for cardiovascular complications in CKD patients.
Abstract 4139371: Treatment of pulmonary arterial hypertension by blocking integrin a5b1, a potential disease-modifying strategy
Authors: Montesinos Monica , Lemay Sarah-Eve , Kapoor Parmita , Rapisardi Hailey , Nguyen Minh Hai , Kim Haejin , Akram Muzaffar , Jain Dhawal , Konopka Elizabeth , Moy Terence I. , Smukste Inese , McTeague T. Andrew , Dowling James , Lama Sujan , Pondish Jessica , Qiao Qi , Monroy Meghan Monroy , Lin Albert , Wang Hua , Boucherat Olivier , Sauvaget Melanie , Potus Francois , Breuils Bonnet Sandra , Theberge Charlie , Provencher Steeve , Ray Adrian , Lippa Blaise , Bonnet Sebastien , Goodwin Bryan , Lu Min
Published: November 2024

Introduction:
Pulmonary arterial hypertension (PAH) is marked by pathological remodeling of distal arteries, driven by hyperplasia of pulmonary arterial smooth muscle cells (PASMCs), dysfunction of pulmonary arterial endothelial cells (PAECs), and increased deposition of the extracellular matrix (ECM).

Hypothesis:
Considering the crucial role of ECM in vascular restructuring, we investigated the potential of therapeutically targeting a5b1, a fibronectin-binding integrin involved in cell proliferation and angiogenesis, for PAH treatment.

Aim:
To evaluate the therapeutic potential of targeting a5b1 for the treatment of PAH.

Methods:
We have developed potent, orally bioavailable small molecule inhibitors (SMis) and monoclonal antibodies (mAbs) targeting a5b1 to evaluate its therapeutic potential. The effect of a5b1 inhibition was assessed in cultured PASMCs, human precision-cut lung slices (PCLS), and a rat Sugen/hypoxia PAH model.

Results:
PAH patients exhibited increased expression of fibronectin and a5b1 in distal pulmonary arteries. Selective inhibition of a5b1 in cultured PASMCs modulated multiple pathways involved in cell cycle regulation at both transcriptional and post-transcriptional levels, thereby blocking cellular proliferation. PCLS treated with a5b1 inhibitors showed decreased expression of pathways involved in ECM deposition and reduced levels of smooth muscle cell markers. In the rat Sugen/hypoxia PAH model, a5b1 inhibition with either an SMi or mAb significantly improved cardiac and vascular function by reducing pulmonary arterial wall thickness, right ventricular hypertrophy, and fibrosis. Cardiac improvement is further evidenced by a reduction in circulating NT-proBNP and NT-proANP levels.

Conclusion:
These findings reveal a previously underappreciated role for a5b1 in PAH pathogenesis and support the potential of a5b1 inhibition as a disease-modifying therapeutic strategy for managing PAH.
Abstract 4139380: A Report of

2000

Consecutive Patients Undergoing Imaging with Pacemakers and ICDs in the MRI Environment; the Additive Value of a Large, Prospective ~20-Year Observational Study
Authors: Biederman Robert , Shah Moneal , Boltralik Mark , Williams Ronald , Lombardi Richard , Mangini Francesco , Doyle Mark
Published: November 2024

Background:
Imaging of conventional PM’s and ICDs are infrequently performed via MRI. While many studies, including the

MagnaSafe
Trial

have unequivocally supported MRI safety in patients with such devices, the
added
clinical value has rarely been considered. Accordingly, we performed an observational, IRB-approved, prospective study to determine the 'Additive Value'
beyond
safety for patients with conventional PM/ICD's undergoing clinical MRI.

We
hypothesize
that MRI in PM/ICD patients is critical to an existing diagnosis and often markedly alters diagnosis and subsequent downstream patient management.

Methods:
An MRI Device exam (GE 1.5T,WI) pioneered by cardiologists (>90% over 10 yrs; 100% over 20 years) was performed. Subsequently, a series of prospective defining questions using Boolean Logic Construct were answered within 1 week of MRI by both MRI technologist and MRI physicians.

Questions
:

1) Did the primary diagnosis change?

2) Did the MRI provide additional information to existing diagnosis?

3) Was the pre-MRI (tentative) diagnosis confirmed?

4) Did subsequent patient management change?

If 'Yes' was answered to any of the above questions, it was considered that MRI was of value to pt diagnosis and/or impending therapy.

Results:
Average MRI: 25±14min for 2,008 consecutive patients of which 1,526 (76%) were neuro/neurosurgery, 141 (7%) were musculoskeletal and 341(17%) were CV cases. Upon review: of the N
euro/neurosurgery
MRIs, 1,376 (89%) provided additional information.

The diagnosis changed in 1018 (74%), while medical therapy changed in 977 (71%). In only 124 (9%) did MRI simply confirm original diagnosis. For
Cardiac
patients, MRI changed the original diagnosis in 235 (69%). MRI did not contribute in 42 (12%) as it was uninterpretable (ICD artifact), while in 64 pts, the diagnosis did not change. Finally, in 146
Orthopedic
pts, MRI provided additional information in 143 (98%) and in 130 (89%), changed pt care, and in 4 pts (3%), simply confirmed the diagnosis. Importantly, with careful attention to device reprogramming and scanner sequences, no safety or device issues were encountered in any patient all with tracking for >1 year.

Conclusion:
Via a dedicated program of MRI in PM/ICD patients adds substantial clinical value to diagnosis and subsequent management justifying ant inherent risk(s). Herein, we propose that yet another impediment to the advancement of CMR-PM/ICD strategies can become routine and often life-changing.
Abstract 4139383: Non-Inferiority Of Extracorporeal Photopheresis To Immunosuppression Therapy In Heart Transplantation Rejection
Authors: Vakhshoori Mehrbod , Abdi pour Amir
Published: November 2024

Background:
Immunosuppressive (IS) therapy is currently used as first-line treatment for heart transplant (HTx) rejection. However, they are not without complications, and less toxic therapies are needed. This study aims to compare extracorporeal photopheresis (ECP) as an adjuvant therapy with standard IS regimens in patients with HTx rejection.

Methods:
This cross-sectional single-center study included HTx patients who underwent ECP in conjunction with standard IS therapy. Patient were matched with regular IS group in a 1:13 ratio based on rejection score. Data on graft function (International Society of Heart and Lung Transplantation (ISHLT) rejection score and left ventricular ejection fraction (LVEF)) at different time points and survival status were collected from the medical records.

Results:
A total of 84 patients met the inclusion criteria (age at rejection diagnosis: 40.4±21.7 years, males: 58.4%). The median (range) of ECP duration in the ECP plus standard IS group was 228.5 (170-295) days. Patients in ECP adjuvant group had lower LVEF and similar rejection score distribution in comparison to the IS group (P= 0.047, and P= 0.707, respectively). However, matching in 1:1 ratio based additionally on age, sex, and race showed similar outcomes between groups (P> 0.05) (
Table 1
&
Figure 1
). Kaplan-Meier analysis revealed similar survival benefits between groups (log-rank P: 0.12) (
Figure 1E
). The multivariate-adjusted odds ratio of graft status, LVEF improvement, all-cause and cardiovascular diseases mortality were not found to be different in the ECP adjuvant group compared to the standard IS group (P= 0.412, P= 0.449, P= 0.418, and P= 0.627 respectively) (
Table 2
).

Conclusions:
ECP adjuvant therapy is non-inferior to standard IS regimen. Considering patients who do not respond well to IS therapy are referred for ECP, this treatment potentially improves their outcomes and reduces the risk of complications associated with heavy immunosuppression. Further studies are required to validate these findings.
Abstract 4139399: Targeting Hepatic Complement C3 Attenuates Pulmonary Arterial Hypertension Phenotype in Rodents
Authors: Keles Merve , Arnold Nadine , West Laura , Turton Helena , Kim Sung-Kwon , Lasaro Melissa , Rammanujam Meera , Chang C-Hong , Wilkins M , Lawrie Allan
Published: November 2024

Background:
Pulmonary arterial hypertension (PAH) is a severe condition characterized by pulmonary vascular remodelling leading to right ventricle failure. Emerging evidence highlights inflammation as crucial pathogenic factor of PAH. Members of the complement pathway have been identified as dysregulated in multiple studies. We aimed to investigate the relative contribution of different complement pathway components in PAH pathogenesis using pre-clinical rodent models.

Methods and Results:
The Sugen 5416 (20 mg/kg, i.p.) plus hypoxia (SuHx) model in both male C57Bl/6 mice (weekly Sugen + 3 weeks hypoxia) and Wistar rats (single Sugen, 3 weeks hypoxia, 6 weeks in room air) were used to assess the effect of complement inhibition on PAH. Targeting the terminal complement pathway with TPP-903, an anti-C5 antibody administered at 3- or 6 weeks, failed to demonstrate any beneficial effects on the PAH phenotype in SuHx rats. To investigate the alternative pathway, we first utilised the mouse SuHx model, targeting hepatic C3 knockdown using anti-C3 siRNA administered 1 week before PAH induction. There was a significant decrease in both the percentage of remodelled vessels and the degree of remodelling but no significant effect on right ventricular systolic pressure (RVSP). To further assess hemodynamic outcomes alongside vascular remodelling, we repeated the use of anti-C3 siRNA (from week 5) in the more severe rat SuHx model. Treatment with anti-C3 siRNA was associated with more than 90% reduction in C3 RNA expression in the liver, as well as around 91% reduction in circulating C3 levels. Considerable improvement in the PAH phenotype, as evidenced by reduction in RVSP (94.63 vs. 69.71 mmHg, p<0.001, n=8), improvement RV cardiac function (RV-fractional area change (RV-FAC%): 33.54 vs. 43.86%, p<0.05, n=8) were associated with reduced pulmonary vascular remodelling (75 vs. 57%, n=4) compared to vehicle treated rats. Furthermore, there was a reduction in cardiac fibrosis in anti-C3 siRNA treated rats, as assessed by Sirius red staining.

Conclusion:
The therapeutic benefits observed in both right ventricular function and pulmonary vasculature emphasize the potential of complement pathway modulation, particularly through hepatic targeting of C3 as an approach for the treatment of PAH. Ongoing investigations aim to uncover the localized mechanisms driving this therapeutic effect, providing valuable insights for future clinical applications.
Abstract 4139400: Transvenous Lead Extraction Outcomes in Hemodialysis Patients: Assessing the Risk of Infection
Authors: Paul Aritra , Hayashi Katsuhide , Baranowski Bryan , Kochar Arshneel , Martin David , Taigen Tyler , Rickard John , Hussein Ayman , Wazni Oussama , Callahan Thomas
Published: November 2024

Introduction:
CIED implant volume remains high, leading to an increase in TLE (Transvenous Lead Extraction) procedures to manage a growing population with aging leads. However, data on TLE outcomes for dialysis patients is limited.

Aims:
To determine if dialysis patients in the current era have worse outcomes after TLE (procedural success rate, major complications, and 30-day all-cause mortality (ACM)); and to find predictors for the same.

Methods:
We included all TLE procedures at our institution between 2013-2022 (n=1614; dialysis=53; non-dialysis=1561). Data was collected retrospectively from electronic medical records. Outcomes were first analyzed for all patients; followed by subgroup analyses for dialysis patients with infection, since that was the most common indication for TLE (48/53; 90.6%). Within the subgroup, we looked at intracardiac mass on echo, positive blood culture, and pocket infection as predictors.

Results:
Mean age of our sample was 62.3 years and 66.8% were male. Lead age and combined lead age were significantly different between dialysis and non-dialysis patients (8.8 vs 5.6 years; p<0.001, and 11.1 vs 16.5 years; p=0.02). Success rate and major complications rate was similar (96.2% vs 95.5%; p=0.8, and 3.8% vs 2.1%; p=0.4), but 30-day ACM rates were significantly worse among dialysis patients (13.2% vs 2%; p<0.001). Multivariate analysis found dialysis, lead extraction due to infection, and NYHA Class 3 or 4 to be independent predictors of 30-day ACM among the entire study population (Table 1). Within the subgroup, only intracardiac mass was associated with significantly worse 30-day ACM (33.1% vs 6.1%; p=0.01), which was confirmed with multivariate analysis [OR=22.4 (1.8-280.4); p=0.02] (Table 2).

Conclusion:
Dialysis is an independent predictor of 30-day ACM after TLE, along with lead extraction due to infection, and NYHA Class 3 or 4. Within the subgroup of dialysis patients with infection, visualization of intracardiac mass on echo is a predictor of 30-day ACM.
Abstract 4139404: Post-Translational Regulation of Larp6 by IGF-1 Modulates Collagen Synthesis in Smooth Muscle Cells
Authors: Zhang Meng , Danchuk Svitlana , Sukhanov Sergiy , Delafontaine Patrice , Higashi Yusuke
Published: November 2024

Introduction:
Vascular smooth muscle cells (SMCs) play a crucial role in atherosclerosis, contributing to plaque stability by forming the main cellular component of the fibrous cap and synthesizing extracellular matrix. We previously showed that insulin-like growth factor-1 (IGF-1) increases expression of the collagen mRNA binding protein La ribonucleoprotein domain family member 6 (Larp6) and of collagen in atherosclerotic plaques. However, molecular mechanisms remain unclear.

Hypothesis:
We hypothesized that IGF-1 increases collagen synthesis via a post-translational regulation mechanism of Larp6.

Methods:
An SMC-specific Larp6 overexpression mouse model (SMC-Larp6) was generated using the Myh11 promoter. Entire aortas and aortic roots were isolated for plaque analysis. IGF-1 was injected in WT mice at a dosage of 1.5 mg/kg. For in vitro assays, human aortic SMCs were transduced with an adenoviral vector to overexpress Larp6 and treated with 50 ng/mL IGF-1 for 18 h.

Results:
SMC-Larp6 mice had no significant change in plaque collagen content. Additionally, IGF-1 increased Larp6 protein but not mRNA levels suggesting that IGF-1 likely regulated Larp6 via a post-transcriptional mechanism. Western blotting identified two major Larp6 bands at 67 kDa and 70 kDa. We observed a clear band shift from the lower to the upper band after IGF-1 treatment, with a concomitant increase in Procollagen I, suggesting that IGF-1 enhances Larp6's role in promoting collagen through post-translational modification. Mass spectrometry analysis revealed multiple phosphorylation sites on the LaM and LSA domains of Larp6, including S451, which is phosphorylated by the IGF-1/PI3K/AKT axis. We also observed this protein modification pattern in mouse aortic tissue lysates following IGF-1 injection.

Conclusions:
IGF-1 regulates Larp6 phosphorylation in SMC, thereby likely playing an important role in IGF-1 induced collagen synthesis. This study provides insight into molecular mechanisms underlying collagen production in SMCs and could inform therapeutic strategies for plaque stabilization.
Abstract 4139421: Rates Of Atherosclerosis Progression In The Absence Of Cardiovascular Events And Cardiovascular Medications On Cardiac Computed Tomography.
Authors: Aldana Jairo , Kinninger April , Krishnan Srikanth , Manubolu Venkat Sanjay , Ghoto Ayesha , Ichikawa Keishi , Mohamed Mostafa , Anderson Lauren , Ramos Juan , Ramirez Noah , Budoff Matthew , Karlsberg Ronald
Published: November 2024

Introduction:
Rates of progression of atherosclerosis have been derived from populations with established atherosclerotic cardiovascular disease and on plaque modifying therapies. However, the rate of atherosclerosis progression in populations with no history of MACE, risk factors or risk modifying interventions is not known. The aim of this study is to determine the rate of progression in healthy populations on serial CCTA.

Aim:
To determine whether in this population, the rates of progression can be classified in slow, intermediate, and rapid.

Methods:
NATURE-CT retrospectively selected 205 participants from two sites in Los Angeles. Subjects underwent at least two CCTA scans, the initial scan showing CAC ≤100, absence of MACE, not placed on lipid modifying therapy in the first and last scan, and at least 2 years apart. Patients with diabetes, familial hypercholesterolemia or chronic kidney disease were excluded. FDA cleared automated software Cleerly Labs (Cleerly.Inc, NY, NY) which quantified percent atheroma volume PAV% from CCTA. Annual change in PAV% is presented by tertile in this lipid-modifying naïve cohort to understand slow, intermediate and rapid plaque progression rates among subjects.

Results:
There were 205 subjects with a mean age of 54.9±10.2 years and 72% (148) were male. Average time between serial CCTA scans was 4.9±2.2 years. Annual change in PAV% was less than 0.075% in the first tertile (mild progression), between 0.075% and 0.275% with intermediate progression (2nd tertile) and those with greater than 0.275% in a rapid group (3rd tertile). The median and interquartile range [IQR] for annualized change in PAV% for slow progression was 0.03 (0.0, 0.05), intermediate progression was 0.17 (0.12, 0.20) and 0.46 (0.35, 0.67) for rapid progressors. The moderate and rapidly progressing subjects were more likely to be male, have higher BMI, triglyceride levels, and baseline plaque. Rapid progressors were more likely to have LAP present.

Conclusions:
Rates of atherosclerosis progression can be classified in slow, intermediate, and rapid progressors, based on a population with low plaque burden in the first scan, no lipid-modifying interventions, and no events. The presence of low-attenuation plaque correlates rapid progression of atherosclerosis and may offer a justification for plaque directed treatment if confirmed with further studies.
Abstract 4139436: Social Determinants of Health and Disparities in Guideline-Directed Medical Therapy Optimization for Heart Failure
Authors: Jacobs Joshua , Ayodele Iyanuoluwa , Bress Adam , Sterling Madeline , Pandey Ambarish , Derington Catherine , Zheutlin Alexander , Shah Kevin , Greene Stephen , Alhanti Brooke , Blanco Rosalia , Fonarow Gregg
Published: November 2024

Introduction:
Less than 20% of eligible patients with heart failure with reduced ejection fraction (HFrEF) receive all four pillars of guideline-directed medical therapy (GDMT). Understanding disparities in sex, race, ethnicity, and adverse social determinants of health (SDoH) is necessary to equitably optimize quadruple therapy.

Methods:
Utilizing the American Heart Association Get With The Guidelines® Heart Failure registry, we conducted a retrospective cross-sectional study to examine the associations between exposures of race and ethnicity, sex, and adverse SDoH (insurance status and a documented social need [any barrier to accessing healthcare]) with quadruple therapy optimization (QTO) at discharge in patients with HFrEF hospitalized between 7/1/2021-9/30/2023. The outcome was a novel QTO score incorporating SGLT2Is as a pillar of quadruple therapy (Figure 1A). Associations between each exposure and QTO score were assessed using multivariable adjusted linear models to calculate adjusted mean differences (AMDs) and 95% confidence intervals (CIs).

Results:
Among 82,637 included patients (median age 66.0 years, 32.5% female, 57.0% non-Hispanic White, 76.4% prior HF), the overall mean QTO score was 56.2% (standard deviation 25.5). The use of each GDMT component is shown in Figure 1B. After adjustment, Non-Hispanic Black (AMD 2.56 percentage points [95% CI, 2.17, 2.96]) and Hispanic individuals (AMD 0.73 percentage points [95% CI, 0.13, 1.33]) had higher QTO scores vs. Non-Hispanic White individuals. Females had higher QTO scores than males (AMD 1.93 percentage points [95% CI, 1.56, 2.29]). Patients with Medicaid/no insurance (AMD -1.30 percentage points [95% CI, -1.71, -0.88]) and Medicare (AMD -1.70 percentage points [95% CI, -2.16, -1.23]) had lower QTO scores vs. private insurance (Figure 1C). Those with vs. without an identified social need had lower QTO scores (AMD -3.40 percentage points [95% CI, -4.10, -2.71]) (Figure 1D).

Conclusion:
Disparities in quadruple therapy optimization were most evident for patients with adverse SDoH. Patients with Medicaid/no insurance, Medicare, or an identified social need had lower QTO scores. Future efforts should focus on reducing these gaps to improve equitable GDMT use.
Abstract 4139438: Prognostic Value of Cardiopulmonary Exercise Testing in a Contemporary Pediatric Fontan Cohort
Authors: Wang Alan , Griffith Garett , Ward Kendra
Published: November 2024

Background:
Peak exercise capacity via cardiopulmonary exercise testing (CPET) has been shown to have prognostic significance in adult Fontan patients.

Aims:
The aim of this study was to determine the role of CPET in predicting death or need for transplantation in pediatric Fontan patients.

Hypothesis:
We hypothesize that patients with lower baseline exercise capacity would have worse outcomes.

Methods:
We performed a retrospective review of pediatric patients ≤ 18 years of age who had a lateral tunnel or extracardiac Fontan and underwent a CPET (respiratory exchange ratio ≥ 1.0) and spirometry between 2004 and 2022. Serial analysis was performed for patients with CPETs ≥ 2 years apart. Restrictive lung pattern was categorized as forced vital capacity (FVC) ≤ 80% predicted with a normal or increased forced expiratory volume in 1s (FEV1)/FVC, obstructive pattern as FEV1/FVC ≤ 80% predicted, and mixed pattern as FVC ≤ 80% predicted and FEV1/FVC ≤ 80%. Cardiovascular adverse events (CAE) included mortality or cardiac transplantation. Univariate regression analysis was performed.

Results:
A total of 114 patients were included. The mean age at baseline CPET was 12.9 ± 2.9 years and average age at Fontan operation was 3.3 ± 1.7 years. The baseline peak oxygen consumption (VO2peak) was 31.7 ± 7.7mL/kg/min (83.5 ± 10.9% predicted) (Table 1). A total of 80/114 patients had reproducible spirometry with 51 (63.8%) being normal, 22 (27.5%) restrictive pattern, 6 (7.5%) obstructive pattern, and 1 (1.3%) mixed pattern. Serial CPETs were performed in 51 of 114 (44.7%) patients with a mean duration between CPETs of 3.5 ± 2.5 years. The percent predicted VO2peak changed by -0.73 ± 5.88% per year. A total of 15 out of 114 patients (13.2%) had CAE over a mean follow up of 7.8 ± 4.7 years. Each 1-minute increase in exercise duration achieved at baseline resulted in a 28.1% risk reduction in CAE.

Conclusion:
Exercise capacity is maintained during the adolescent years in a contemporary cohort of pediatric Fontan patients. A higher baseline exercise duration is associated with a lower risk for future CAE. A majority of pediatric Fontan patients had normal spirometry.