bluuebunny/crossref_metadata_2025 huggingface dataset:
Camptodactyly-Arthropathy-Coxa Vara-Pericarditis Syndrome Caused by Truncating Mutations in the Prg4 Gene: Case Series and Literature Review
Authors: Ağır Hatice , Sunar İsmihan , Mutlu Mehmet Burak
Published: November 2024

Introduction: Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is an autosomal recessive condition characterized by early-onset camptodactyly, noninflammatory arthropathy, coxa vara deformity, and, rarely, pericardial effusion. The disease gene has been assigned to human chromosome regions 1q25-q31, and truncating mutations have been identified in the proteoglycan-4 (PRG4) gene formerly known as megakaryocyte stimulating factor gene. Methods: A literature review was performed with the findings in patients in terms of CACP syndrome. Also, whole-exome sequencing was performed for all cases. Segregation analyses of the detected variants were performed according to the possibilities. Results: We present 3 Turkish patients with CACP syndrome mimicking juvenile idiopathic arthritis (JIA). All patients were exposed to biologic therapy due to recalcitrant JIA. We have detected two pathogenic PRG4 variants. Case 3 had a novel pathogenic PRG4 variant not reported for the CACP syndrome so far. These two variants cause premature truncation of the protein. A deletion was detected in case 1 in the homozygous state in the PRG4 gene (NM_005807.6: c.3848del, p.Gly1283GlufsTer6, chr1-186281360-G-). A previously described deletion was detected in case 2 and case 3 in the homozygous state in the PRG4 gene (NM_005807.6: c.1910_1911delCT, p.Pro637ArgfsTer9, chr1-186276761-CT). Conclusion: In the current study, we report three pathogenic PRG4 variants including a novel mutation. We consider that a detailed anamnesis, including kinship and meticulous physical examination of camptodactyly in the absence of inflammatory response, may reveal CACP syndrome masquerading as JIA. The PRG4 gene analysis presents the early diagnosis for patients and prenatal counseling and preimplantation genetic diagnosis for carrier families.
Abstract 4138152: Impact Of Peripheral Arterial Disease On Outcomes In Patients With Acute Coronary Syndrome: A Meta-Analysis And Systemic Review
Authors: Shafique Nouman , Akbar Usman , Umer Ahmed Muaaz , Ullah Aman , Haider Ali , Muhibullah Fnu , Shafique Adeena , Khan Ali Raza , TAHIR RANA MUHAMMAD , Latif Muhammad Haris , Nawaz Hassan , Shafiq Iqra , Ur Rehman Atta , Islam Zaigham ul , Abbas Johar , Shahnawaz Waqas , Akram Muhammad Omar , Elsayed Razan , Raza Munis , Munir Bilal
Published: November 2024

Background:
Peripheral artery disease (PAD) is associated with worse outcomes in patients with underlying coronary artery disease (CAD). While the impact of PAD in stable CAD is well-studied, data on the impact of concomitant PAD in acute coronary syndrome (ACS) patients are limited. Our meta-analysis assesses cardiovascular and clinical outcomes in ACS patients with PAD compared to those without PAD.

Methods:
We conducted an extensive search using PubMed, EMBASE, and Cochrane Library for studies published prior to June 1, 2024, evaluating clinical and CV outcomes in patients diagnosed with PAD and concomitant ACS. Data were extracted and analyzed using R (v.4.3). Pooled proportions with 95% confidence intervals (95% CIs) were calculated using a random effects model. Odds ratios (ORs) with 95% confidence intervals were used as effect measures for dichotomous variables. Our outcomes of interest were all-cause mortality, major adverse cardiovascular events (MACE), recurrent CV events, and major bleeding.

Results:
We identified four studies, including 3,860,564 patients. Our inclusion criteria were adults (≥18 years) recently hospitalized or discharged with ACS (unstable angina, non-ST-elevation myocardial infarction, and ST-elevation myocardial infarction). PAD was defined as intermittent claudication and/or previous revascularization. The PAD group exhibited significantly higher likelihood of adverse outcomes compared to the non-PAD group. Specifically, the odds of mortality were significantly higher in the PAD group (OR: 2.79 [1.41, 5.53]; I2=99%; p=0.003), however there was substantial heterogeneity among the studies. The odds of MACE were also higher in the PAD group (OR: 2.12 [1.51, 2.96]; I2=71%; p<0.0001), as were the odds of recurrent CV events in the PAD group (OR: 1.72 [1.52, 1.94]; I2=0%; p<0.00001). Additionally, the PAD group had significantly increased odds of major bleeding events (OR: 2.48 [1.85, 3.33]; I2=0%; p<0.00001).

Conclusion:
Our meta-analysis demonstrates that PAD significantly worsens cardiovascular and clinical outcomes in ACS patients, highlighting the need for identification and targeted management strategies in this high-risk population. Future research should focus on optimizing interventions to improve prognosis for ACS patients with PAD.
Abstract 4138248: Outcomes of Patients with Radiation-Associated Cardiac Disease Undergoing Cardiothoracic Surgery: Development of a Disease Specific Risk Score
Authors: Gaballa Andrew , Jadam Shada , Wang Tom Kai Ming , Unai Shinya , Koprivanic Marijan , Roselli Eric , Xu Samantha , Ospina Susan , Collier Patrick , Griffin Brian , Desai Milind
Published: November 2024

Background:
Radiation-associated cardiac disease (RACD) has significant long-term mortality and morbidity, often requiring cardiac surgery(CS).

Hypothesis:
We sought to study factors associated with longer-term survival in RACD patients and develop a specific risk score associated with 5-year survival following CS.

Methods:
This was an observational cohort study of 351 patients with documented RACD (252 [72%] had mantle radiation for lymphoma at a mean of 18 years prior), who underwent CS at a tertiary care center between 1991-2018. Clinical characteristics were collected, and Society of Thoracic Surgeons (STS) score was calculated. The primary endpoint was mortality. Multivariable analysis for 5-year mortality was performed using age, sex, history of lymphoma, New York Heart Association class, prior cardiac surgery, atrial fibrillation, constriction, chronic pulmonary disease, serum creatinine, left ventricular ejection fraction, right ventricular systolic pressure and valvular surgery(aortic, mitral or tricuspid).

Results:
Clinical characteristics are shown in Figure 1. Mean follow-up was 6.2±4.6 years&5-year mortality occurred in 123 (35%) patients (7 [2%] in-hospital deaths). Cox 5-year survival analysis results are shown in Figure 2A. A receiver operator curve analysis for 5-year mortality showed an area under curve of 0.70 (95% confidence interval 0.64-76, p<0.001). Subsequently, a 5-year risk score (0-7 points) was generated (Figure 2 A); with an increasing risk of mortality at 5 years, based on increasing risk score (Figure 2C). Cardiac reoperation was not associated with worse outcomes.

Conclusion:
RACD patients undergoing CTS have a high rate of 5-year mortality, despite a low baseline STS score&perioperative mortality. A novel RACD-specific risk score (incorporating higher age, abnormal renal/pulmonary, constrictive pericarditis&need for concomitant mitral valve surgery) provides good discrimination for 5-year survival&could be used for shared-decision making.
Abstract 4138268: The Use of Mavacamten for Management of Post TAVR Obstruction: A Novel Approach to Treatment
Authors: Hart Hannah , Grewal Prabhjot , Sud Karan , Argulian Edgar , Casso Abel
Published: November 2024

Background:
Treatment of left ventricular outflow tract (LVOT) obstruction involves a combination of negative inotropic agents. However, these therapies have limitations which may result in insufficient control of symptoms, leading to more invasive options such as surgical septal myectomy or septal alcohol ablation. Mavacamten, a cardiac myosin inhibitor, is currently approved for the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). We present a case of a patient treated with mavacamten in addition to β-blockers (BB) for management of post-TAVR LVOT obstruction.

Case:
A 76 year old female with a past medical history of hypertension, severe aortic stenosis, and coronary artery disease underwent a Medtronic Evolut TAVR in March 2022. Her TTE post TAVR showed LVOT peak gradient greater than 100 mm Hg, LVEF 75% and severe eccentric mitral regurgitation secondary to systolic anterior motion (SAM) of the mitral valve (MV). After multidisciplinary discussion, the patient was discharged on maximally tolerated BB therapy. Follow up TTE showed persistent obstruction and gradients, so diltiazem was added to her regimen. Her subsequent TTE showed a peak LVOT > 100 mmHg at rest, and severe MR. Given persistent findings, she was started on mavacamten, continued on metoprolol, and tapered off of diltiazem. Her TTE two months after initiation of mavacamten revealed resolution of LVOT gradients, reduction of MR to mild and normal LV and TAVR function. She tolerated the therapy well and endorsed ongoing symptomatic improvement on subsequent follow up.

Discussion:
With the increasing use of TAVR therapy, there has been a corresponding rise in cases of post-TAVR obstruction that must be managed. As demonstrated by this case, management with BB therapy alone may be suboptimal. Although mavacamten is currently approved in patients with HCM, the obstruction in post-TAVR patients is functionally similar. Thus, this medication was trialed as a supplemental treatment in this patient and yielded positive results. This case highlights the potential benefit of extending use of mavacamten alongside β-blocker therapy for this patient population and suggests the need for future studies.
Abstract 4138269: The Association Between Automatically Assessed Broad P-wave and Cardiovascular Events in Patients with Cardiovascular Risks
Authors: Yokota Ayako , Kabutoya Tomoyuki , Hoshide Satoshi , Kario Kazuomi
Published: November 2024

Background:
A broad P wave in electrocardiography reflects atrial remodeling and is associated with cardiovascular events. Although there are several reports on the association between a broad P wave and cardiovascular events, the association between automatically assessed P-wave duration and cardiovascular events in cardiovascular high-risk patients has not been clarified.

Hypothesis:
We hypothesized that a greater automatically assessed P-wave duration would be associated with cardiovascular events in patients with cardiovascular risk factors.

Methods:
We included 4,654 patients with access to automated electrocardiography (ECG) analysis of those in the Cardiovascular Prognostic Coupling Study in Japan (a registry of subjects with one or more cardiovascular risk factors, excluding patients with atrial fibrillation). Twelve-lead ECG was conducted, and the P-wave duration in each lead was analyzed automatically using the 12-lead ECG Analysis system (Fukuda Denshi, Tokyo). We selected the maximum P wave duration (Pmax) among the 12 leads. The primary endpoint was a composite endpoint (cardiovascular death, nonfatal myocardial infarction/stroke), and the secondary endpoint was heart failure hospitalization. We assessed two P-wave cut-offs (Pmax ≥ 140, 150 msec) in relation to cardiovascular events.

Results:
There were 218 patients with Pmax ≥140 ms and 123 patients with Pmax ≥150 ms. N-Terminal pro brain natriuretic peptide (NT-proBNP) was significantly higher in patients with Pmax ≥140 ms than in those with Pmax <140 ms (median 134.0 vs. 65.7 pg/mL, p<0.001). NT-ProBNP was also higher in patients with Pmax ≥150 ms than in those with Pmax <150 ms (median 192.0 vs. 66.9 pg/mL, p<0.001).

The mean follow-up period was 53 ± 17 months. The primary endpoint occurred in 180 cases and the secondary endpoint in 73 cases. A broad P-wave defined as Pmax ≥140 ms was independently associated with the primary endpoint (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.04–2.70, p=0.034) but not with the secondary endpoint (HR 1.96, 95% CI 0.99–3.90, p=0.055) after adjustment for covariates including NT-proBNP. A broad P-wave defined as Pmax ≥150 ms was independently associated with both the primary endpoint (HR 2.08, 95% CI 1.06–4.09, p=0.034) and the secondary endpoint (HR 3.22, 95% CI 1.38–7.52, p=0.007).

Conclusions:
Automatically assessed P-wave duration of Pmax ≥ 150 ms was a significant predictor of cardiovascular events and heart failure.
Abstract 4138335: A drug target Mendelian randomization study of triglyceride lowering therapies for aortic stenosis
Authors: Ciofani Jonathan , Han Daniel , Gill Dipender , Rao Karan , Allahwala Usaid , Bhindi Ravinay
Published: November 2024

Introduction:
Large observational and Mendelian randomization (MR) studies have demonstrated a strong association between elevated triglycerides (TG) and risk of aortic stenosis (AS). However, at present there remains no evidence for the use of lipid-lowering therapies to prevent or treat AS. To address this gap, we used a drug target MR approach to investigate whether emerging TG lowering therapies may reduce the risk of AS.

Methods:
We collected summary statistics for TG levels and AS from genome-wide association studies including 1,253,277 and 653,867 European participants, respectively. We first performed conventional MR techniques to investigate a causal relationship between TG levels and AS risk. Next, we identified genetic proxies for the TG-lowering therapies fenofibrate, volanesorsen and evinacumab as single nucleotide polymorphisms (SNPs) within 200kb of the target genes (
PPARA, APOC3
and
ANGPTL3
, respectively) which were also significantly associated with TG at p<5x10
-8
and clumped using threshold r
2
<0.1. Inverse-variance weighted (IVW) was the primary analysis method. We then performed sensitivity analyses including weighted-median and MR-Egger. Additional outlier-exclusion analyses were performed using MR-PRESSO and Cook’s distance. Finally, we completed sensitivity analyses using a more stringent clumping threshold of r
2
<0.01.

Results:
Consistent with previous findings we found genetically predicted TG levels were significantly associated with increased risk of AS (IVW: OR 1.28 per standard deviation increase in genetically predicted log TG level, 95% CI 1.18-1.39, p<0.0001). We further found that genetically proxied volanesorsen was significantly associated with reduced risk of AS (OR 0.54, 95% CI 0.39-0.75, p=0.0002), which was robust in all sensitivity analyses. We did not find evidence of a causal relationship between genetically proxied fenofibrate (IVW: OR 0.50, 95% CI 0.09-2.76, p=0.43) or evinacumab (IVW: OR 1.03, 95% CI 0.73-1.44, p=0.88) and risk of AS.

Conclusions:
Genetically proxied
APOC3
inhibition, but not
PPARA
or
ANGPTL3
, was robustly associated with reduced risk of AS. This suggests that
APOC3
inhibition may be a therapeutic opportunity for AS management and warrants further research in the clinical trial setting.
Abstract 4138339: Abatacept prevents anti-PD-1-induced inflammatory heart failure development after myocardial ischemic injury in mice
Authors: Gergely Tamás , Drobni Zsofia , Kovacs Tamas , Sayour Nabil , Toth Viktoria Eva , Onodi Zsofia , Kocsis Marton , Fekete Nora , Pallinger Eva , Buzas Edit , Neilan Tomas , Ferdinandy Peter , Varga Zoltan
Published: November 2024

Introduction:
Immune checkpoint inhibitors (ICI), such as anti-PD-1 monoclonal antibodies are increasingly used in anti-cancer therapy. However, several cardiovascular adverse effects can occur with the use of ICIs, including new-onset heart failure.

Hypothesis:
We hypothesized that prior myocardial ischemic injury could exacerbate cardiac dysfunction and inflammation caused by anti-PD-1 treatment. Moreover, we investigated whether abatacept, a T-cell co-stimulation blocker, can prevent ICI-induced cardiac effects.

Methods:
To induce reversible cardiac ischemia, C57Bl/6J mice were treated with isoprenaline (ISOP group) or with PBS (CON group), followed by 16 weeks of recovery period. Following this, mice from both groups were divided into three further treatment groups: isotype control, anti-PD-1, or anti-PD-1 combined with abatacept, and were treated for two weeks, with three weekly intraperitoneal injections. Echocardiography was performed to evaluate cardiac function while myocardial inflammation was assessed by qRT-PCR and immunohistochemistry. Flow cytometry and Western blot were used to investigate changes occurring in the thymus.

Results:
Mice with normal heart function but with prior ischemic injury and anti-PD-1 treatment (ISOP + anti-PD-1) showed significantly decreased fractional shortening and cardiac index on echocardiography, while in animals with abatacept co-treatment (ISOP+anti-PD-1+abatacept) cardiac function was not altered. Increased immune cell infiltration was seen in the myocardium of the ISOP+anti-PD-1 treated group compared to CON animals, including T-cells and macrophages, with increased expression of pro-inflammatory cytokines, while co-treatment with abatacept ameliorated the inflammatory response. In the thymus, increased expression of PD-1 was found after abatacept co-treatment.

Conclusion:
Prior myocardial ischemic injury was associated with cardiac dysfunction and inflammation after anti-PD-1 treatment, which was ameliorated by abatacept co-treatment. Patients with prior cardiac ischemic events may be at greater risk for developing ICI-induced cardiotoxicity, including new-onset HF.
Abstract 4138407: Exome-wide association study of over a million individuals identified effector genes and variants for blood lipids
Authors: Koyama Satoshi , Yu Zhi , Choi Seung Hoan , Jurgens Sean , Selvaraj Margaret , Klarin Derek , Huffman Jennifer , Trinh Michael , Ravi Akshaya , Dron Jacqueline , Spinks Catherine , Surakka Ida , Hornsby Whitney , Damrauer Scott , Chang Kyong-Mi , Assimes Themistocles , Tsao Philip , Rader Daniel , Kim Kelly , Peloso Gina , Ellinor Patrick , Sun Yan , Wilson Peter , Natarajan Pradeep
Published: November 2024

Background:
Inherited hypercholesterolemia is an important Mendelian condition associated with early onset myocardial infarction. However, current genetic diagnostic criteria only partially explain severe clinical hypercholesterolemia. Furthermore, current pathogenicity categorizations do not consistently inform prognosis, but quantification is limited by scarcity of such rare variants.

Aim:
Exploiting populations scale genotype/phenotype data, to determine the architecture of the genetic variants associating with blood lipid levels with quantitative assessments.

Methods:
Here, we discovered and characterized rare coding alleles contributing to genetic dyslipidemia, a principal risk for coronary artery disease, among over a million individuals combining two large contemporary genetic datasets (Million Veteran Program N = 626,554 and UK Biobank, N = 431,026).

Results:
Testing 2,869,269 rare (minor allele frequency < 1%), coding variants, we identified 793 exome-wide significant associations (
P
< 4.4 × 10
-11
), including 8 previously undiscovered loci. Associated alleles are highly enriched in functional variant classes; high confidence predicted loss of function, deleterious missense, and cryptic splicing, showed significant and recessive associations, had similar effects across populations. Overall, rare variants contributed to additional > 16% of genetic trait variances on top of common genetic variants. The effect estimates of associated signals confirmed and refined curated pathogenic database, highlighted by the identification of African or South Asian specific pathogenic alleles previously controversial in its pathogenicity.

Conclusion:
This study provides resources and insights for understanding causal mechanisms and quantifying the expressivity of rare coding alleles for blood lipids by large scale sequencing study. Furthermore, identifying and characterizing population enriched variants, our study underscored the importance of multi-population rare variant study.
Abstract 4138606: Toll-like Receptor 4 Signaling Establishes Trained Innate Immunity Through Interferon-Mediated Epigenetic Modifications Leading to Cardioprotection in a Stress-induced Cardiomyopathy Model
Authors: Lim Kenji Rowel , Amrute Junedh , Kovacs Attila , Diwan Abhinav , Mann Douglas
Published: November 2024

Introduction:
The mechanisms responsible for establishing preconditioning-induced cardioprotection remain unknown. We have shown that a high dose of isoproterenol (ISO) induces cardioprotection against a second ISO dose in mice. The durability of protection and the lack of an innate immune response suggests trained immunity as a novel cardioprotective mechanism.

Hypothesis:
We hypothesize that cardioprotection is conferred through trained immunity, by interferon signaling downstream of necrotic cardiac material-mediated Toll-like receptor 4 (TLR4) activation.

Methods:
Wild-type C57BL/6J mice were intraperitoneally injected with TLR agonists or diluent, and challenged with 300 mg/kg ISO 7 days later. Mice were assessed by 2-D echocardiography, serum cardiac troponin levels, flow cytometry immune cell counts, and Multiome (single nuclei RNA+ATAC) sequencing.

Results:
The TLR4 agonist lipopolysaccharide (LPS) induced cardioprotection against ISO injury, with mice having enhanced survival (P=0.049) and no changes in cardiac troponin levels (P>0.99), cardiac neutrophil influx (P>0.99) or left ventricular motion (P=0.057) relative to baseline values before injury. Treating LPS-injected mice with β-glucan reversed the effects of LPS on immune cells and abolished cardioprotection. Multiome analysis of genes linked to chromatin peaks with increased accessibility in LPS+vehicle (protected) compared to LPS+β-glucan and diluent control (non-protected) hearts revealed the interferon pathway to be up-regulated across all major cell types. Modulation of interferon signaling with monoclonal antibodies against type 1+2 interferon receptors abolished cardioprotection in LPS-treated mice, whereas pre-treatment with recombinant type 1+2 interferons induced cardioprotection. Importantly, interferon-treated hearts shared similar chromatin accessibility features and enriched transcription factor motifs, including interferon-specific motifs, with LPS-protected hearts across cell types, particularly among non-cardiomyocytes.

Conclusions:
TLR4-induced interferon signaling is sufficient and in part necessary for cardioprotection against ISO injury. Moreover, our findings show that epigenetic modifications downstream of interferon signaling lead to cardioprotection consistent with trained innate immunity.
Abstract 4138965: The Triglyceride-Glucose Index and Type 2 Diabetes are Mutually Independent Predictors of Major Cardiovascular Events in Patients With Established Cardiovascular Disease
Authors: Plattner Thomas , Larcher Barbara , Mader Arthur , Vonbank Alexander , Leiherer Andreas , Muendlein Axel , Drexel Heinz , Saely Christoph H
Published: November 2024

The triglyceride-glucose index (TyG) is a validated biomarker of insulin resistance. Its power to predict major cardiovascular events (MACE) in patients with established cardiovascular disease is unclear and is addressed in the present study.

We enrolled 1790 consecutive patients, 1481 with angiographically proven CAD and 309 with sonographically proven PAD. Prospectively, MACE were recorded over a mean follow-up period of 10.7±5.0 years.

At baseline, the TyG index was significantly higher in patients with T2DM (n=586) than in non-diabetic subjects (9.2±0.7 vs. 8.7±0.5; p<0.001). During follow-up, 916 of our patients suffered MACE. The event rate was significantly higher in patients with T2DM than in non-diabetic subjects (60.2 vs. 47.7%; p<0.001). The TyG index in Cox regression models adjusting for age, sex, hypertension, smoking, body mass index, and LDL cholesterol independently predicted MACE in the total study population (standardized adjusted HR 1.21 [1.12-1.30], p<0.001); HRs in patients without T2DM and in diabetic subjects were 1.08 [0.95-1.25], p=0.272 and 1.16 [1.03-1.31], p=0.013, respectively, with no evidence of an interaction between TyG and T2DM (p=0.093). With T2DM additionally entered into the regression model, TyG in the total study population predicted cardiovascular events independently from the presence of T2DM (HR 1.12 [1.03- 1.23], p=0.008), while T2DM remained independently predictive of MACE after adjustment for TyG (HR 1.42 [1.19-1.67]; p<0.001).

From our data we conclude that the TyG index and T2DM are mutually independent predictors of MACE in patients with CAD.
Abstract 4138970: A Novel Cardiac Simulator "ped UT-Heart" to Support Decision-Making in Surgical Procedures for Complex Congenital Heart Disease
Authors: Shiraishi Isao , Kurosaki Kenichi , Iwai Shigemitsu , Washio Takumi , Sugiura Seiryo , Hisada Toshiaki
Published: November 2024

Background:
To support the surgical decision-making for complex congenital heart disease (CHD), a novel computer-based cardiac simulator called "ped UT-Heart" has been developed, in which a patient-specific finite element model simulates cardiac functions and predicts hemodynamics of different virtual surgeries.

Objective:
To validate the accuracy, usefulness, and safety of the “ped UT-Heart“ simulation system.

Methods:
First, retrospective validation studies of pre- and post-operative simulation (n=10) were performed by comparing virtual simulation data with real patient catheter data. Subsequently, a single-arm, prospective, multicenter clinical study (jRCTs052210139) was conducted in 16 patients with complex CHD (Table 1). The primary endpoint was defined as an overall rating of essential or very useful on a 5-point Likert scale.

Results:
Pre- and post-operative simulation data correlated well with patient catheter data (Figure 1). In the clinical trial, four patients were excluded due to delayed surgery, and the remaining 12 patients (median age, 2y8m) were assessed for usefulness. There were no adverse events associated with the simulation system. Nine of the twelve patients (>60%) were rated as “Essential” or “Very useful“, and the lower limit of the 95% CI was 42.8% (>30%), indicating that the results met the primary endpoint. As a representative case (ccTGA, 5y), the surgeon selected a double switch operation with VSD augmentation according to the post-operative simulation (Figure 2). The patient did well after the surgery with no significant hemodynamic problems.

Conclusions:
The "ped UT-Heart" is a safe, reliable, and useful cardiac simulator for supporting decisions of surgical procedures in complex CHD.
Abstract 4138985: Prescription Pattern, Medication Burden, and Transplant-Free Survival in the Adult Fontan Population
Authors: Freddo Andrew , Eron Molly , Mondal Antara , Zavez Alexis , Denduluri Srinivas , Partington Sara , Ruckdeschel Emily , Tsao Allison , Ortega-Legaspi Juan , Kim Yuli , Vaikunth Sumeet
Published: November 2024

Introduction:
There are limited data on the medications taken by patients with Fontan circulation in adult congenital heart disease (ACHD) clinics.

Research Questions/Hypothesis:
We aim to describe the type and frequency of medications prescribed to adults with Fontan circulation and hypothesize that patients with higher medication burden have worse outcomes.

Methods:
We conducted a retrospective cohort study of adults with Fontan circulation followed in an outpatient ACHD clinic between 2009 and 2023. Demographics, clinical variables, and all prescribed outpatient cardiac medications were abstracted. The outcome of interest was transplant-free survival. Survival analysis was performed to evaluate the impact of medication type and burden on survival.

Results:
There were 429 patients (55.2% male, 72.5% White, 49.7% systemic left ventricle) with median age 29 years (IQR 25-35) at last visit. The commonly prescribed medication classes were antiplatelet agents (74.6%) followed by angiotensin converting enzyme inhibitors or angiotensin receptor blockers (59.0%), beta blockers (44.8%), anticoagulants (44.0%), loop diuretics (39.6%), mineralocorticoid receptor antagonists (MRA) (31.5%), antiarrhythmics (19.6%), and pulmonary vasodilators (16.1%). There were a smaller number of patients prescribed sacubitril-valsartan (0.9%) and sodium glucose cotransporter 2 inhibitors (1.9%). Being prescribed loop diuretics, antiarrhythmics, pulmonary vasodilators, or MRA was associated with decreased transplant-free survival (Table). There is a stepwise decrease in transplant-free survival with increasing number of cardiac medication classes prescribed (Figure).

Conclusions:
We report one of the first large-scale studies of prescription patterns in adult patients with Fontan circulation in a single ACHD clinic. We demonstrate an association between increasing number of medications with transplant-free survival.
Abstract 4139036: Predictors of Flow Improvement Following Transcatheter Aortic Valve Replacement in Patients with Low-Flow Low-Gradient Aortic Stenosis
Authors: Besir Besir , Majeed-Saidan Maryam Muhammad Ali , Rajendran Judah , Lomaia Tamari , Kathavarayan Ramu Shivabalan , Iskandar Odette , Yun James , Harb Serge , Miyasaka Rhonda , Reed Grant , Puri Rishi , Krishnaswamy Amar , Kapadia Samir
Published: November 2024

Background:
Patients with low-flow low-gradient (LFLG) aortic stenosis (AS) are at risk of worse outcomes following transcatheter aortic valve replacement (TAVR). Flow is known to improve after TAVR, however the clinical and echocardiographic characteristics correlating with flow improvement in patients with LFLG AS are still unclear.

Hypothesis:
Some baseline and discharge clinical and echocardiographic characteristics correlate with flow improvement in patients with LFLG AS post-TAVR.

Aims:
The present study sought to explore the clinical and echocardiographic characteristics correlating with flow improvement in patients with LFLG AS post-TAVR.

Methods:
This is a retrospective cohort of patients >18 years of age who underwent TAVR at Cleveland Clinic between 2016 and 2020. Only patients with aortic valve (AV) area <1 cm
2
, AV mean gradient <40 mmHg, and stroke volume index (SVI) <35 mL/m
2
were included. Patients were classified into 2 groups according to whether SVI improved by 20% or more at the 30-day follow-up. Patients who underwent valve-in-valve TAVR were excluded. Binary logistic regression was used to evaluate the predictors of flow improvement.

Results:
A total of 2630 patients underwent TAVR between 2016 and 2020. The study included 633 patients. 228 patients (36%) had SVI improvement by 20% or more. Male sex (odds ratio (OR)=1.89, p=0.01), left ventricular ejection fraction (LVEF) improvement by 10% or more 1 month post-TAVR (OR=6.93, p<0.001), and lower baseline SVI (OR=0.81, p<0.001), were statistically significant predictors of flow improvement, whereas moderate to severe tricuspid regurgitation (TR) at discharge was a statistically significant predictor of no improvement in flow.

Conclusions:
The present study demonstrates that male sex, LVEF improvement post-TAVR, and lower baseline SVI are associated with flow improvement, whereas moderate to severe TR at discharge is associated with no flow improvement post-TAVR in patients with LFLG AS.
Abstract 4139090: Cardiovascular Outcomes in Patients with Giant Cell Arteritis: A Meta-Analysis
Authors: Akbar Usman , Umer Ahmed Muaaz , Muhibullah Fnu , Shafique Nouman , Ali Sarmad , Naseer Faisal , Nawaz Hassan , Lohana Abhi , Ahmed Faizan , Naveed Muhammad Abdullah , Khan Muhammad Aslam , Cheshire Michael
Published: November 2024

Background:
Cardiovascular outcomes in patients with giant cell arteritis (GCA) compared to non-GCA patients remain a significant concern due to the inflammatory nature of GCA and its potential impact on cardiovascular health. We conducted the first meta-analysis of its kind to compare cardiovascular events in the GCA versus non-GCA populations.

Methods:
A meta-analysis was conducted on studies comparing cardiovascular outcomes between GCA and non-GCA cohorts. The analysis focused on three outcomes: major cardiovascular events (MACE), cerebrovascular accidents, including stroke or hemorrhage (CVA), and myocardial infarction (MI). The studies provided odds ratios (ORs) with 95% confidence intervals (CIs) to quantify the association between GCA and cardiovascular events.

Results:
This meta-analysis compared cardiovascular outcomes between patients with giant cell arteritis (GCA) and non-GCA patients across several studies, including a total population of 30,672 participants. The results indicated that GCA patients have a significantly higher risk of composite cardiovascular events, with a pooled odds ratio (OR) of 1.44 (95% CI: 1.10-1.89, p = 0.008), despite significant heterogeneity (I2 = 77%). Additionally, GCA patients were found to have a higher risk of cerebrovascular accidents (CVAs) with an OR of 1.27 (95% CI: 1.08-1.48, p = 0.004), showing consistent results across studies (I2 = 0%). For myocardial infarction (MI), GCA patients also faced a higher risk, with a pooled OR of 1.56 (95% CI: 1.09-2.25, p = 0.02), although there was considerable variability in the study results (I2 = 82%).
(Figures 1, 2, and 3).

Conclusion:
GCA patients are at higher risk for composite cardiovascular outcomes and CVAs compared to non-GCA patients, but there is no significant difference in MI risk. The variability in study results indicates a need for further research to confirm these findings and understand the underlying mechanisms.
Abstract 4139230: Mapping the Molecular Progression of Human Coronary Atherosclerosis Confirms Key Role of Smooth Muscle Cell Phenotype and Highlights Novel Regulators of Phenotypic Fate
Authors: Parker Sarah , Mao Chunhong , Wang Yizhi , Seals Austin , Kim Do-Kyun , Lu Yingzhou , bhardwaj saurabh , Du Dongping , Karere Genesio , Caudell David , Vanderheide Richard , Hixson James , Van Eyk Jennifer , Wang Yue , Herrington David
Published: November 2024

Background:
clarity in the molecular mechanisms contributing to pre-clinical stages of coronary atherosclerosis is needed to develop novel early diagnostic tools and more effective preventive interventions.

Methods:
We completed untargeted proteomic and RNA expression analysis on proximal coronary arterial (CA) tissues from young adults who died of trauma with no
antemortem
suspicion of coronary disease (n=322, mean age (range): 34.1 yrs. (15-59); sex: M-239, F-83; race: W-218, B-88, other-16), including n=180 (56%) with morphologic evidence of pre-clinical atherosclerosis. Proteomic data (n=1900 proteins) were analyzed using manifold learning and unsupervised latent feature (LF) detection methods to define the pseudo-temporal progression of disease from normal to advanced atherosclerosis and to identify molecular drivers of disease initiation and progression. Correlation and network mapping of the mRNA data (n=16,707 transcripts, including n=1707 annotated transcription factors [TFs]) from the same arterial samples was used to define the transcriptional regulatory networks (TRNs) associated with the observed proteomic LF dynamics.

Results:
Four of seven identified LFs had a significant (FDR <p.01) association with plaque progression. Among these, a standout LF clearly represented quiescent, contractile smooth muscle cells (SMC) with progressive and then poignantly reduced abundance in late-stage lesions. This LF was enriched with proteins related to cell adhesion and SMC contractility, including 14 previously implicated in the pathogenesis of atherosclerosis via GWAS analyses. Analysis of TRNs revealed 36 regulatory TFs with (1) a predicted binding site in the promotor of SMC LF marker proteins, (2) observed expression that was strongly associated with this SMC LF and (3) significant correlation between predicted activity and observed abundance, including the established SMC phenotype regulator SRF. Expression of regulatory TFs and SMC LF markers in public single-cell RNAseq data from normal and atherosclerotic human coronary tissues suggested both SMC intrinsic and cell-cell crosstalk TRNs.

Conclusions:
The pseudotemporal pattern of the SMC LF was consistent with SMC phenotype changes as early initiating events in atherosclerosis of the CA. Therapies to promote or inhibit activity of these identified TFs may prevent against early lesion formation and atherosclerosis progression by supporting SMC phenotype stability.
Abstract 4139237: Medical Therapy and Outcomes in Patients with Critical Limb Threatening Ischemia Randomized to an Everolimus Eluting Resorbable Scaffold or Angioplasty in the LIFE-BTK Randomized Trial
Authors: Bonaca Marc , DeRubertis Brian , Varcoe Ramon , Parikh Sahil
Published: November 2024

Introduction:
Patients with critical limb-threatening ischemia (CLTI) are at high risk of CV and limb outcomes yet established medical therapies are underutilized. The LIFE-BTK trial demonstrated that a drug-eluting resorbable scaffold (DRS) was superior to angioplasty (ANG) for limb outcomes. The background use of optimal medical therapy (OMT) and the effect of DRS vs. ANG based on OMT at baseline has not been described.

Methods:
Patients were randomized 2:1 to DRS vs. ANG, respectively. Sites reported baseline medications. OMT was defined as use of at least one antithrombotic and LDL-C lowering agent. The primary outcome was a composite of amputation above the ankle of the target limb, occlusion of the target vessel, clinically driven revascularization of the target lesion, and binary restenosis of the target lesion. A key secondary outcome was major amputation, target vessel re-occlusion, or clinically driven target lesion revascularization. Data are presented as event rates and relative risk (RR).

Results:
A total of 261 patients were randomized with follow up through 1 year. DRS was superior to ANG for the primary outcome (p<0.001). Approximately 80% of patients received OMT at baseline with use similar between groups (Panel A). Increased adherence was associated with a history of hyperlipidemia and a history of coronary artery disease (CAD). In the ANG arm, use of OMT was associated with lower risk of the primary efficacy outcome (Panel B) and key secondary efficacy outcome (Panel C). Use of DRS was superior to ANG overall with consistent effects in those receiving OMT (RR 0.52, 95% CI 0.36 – 0.75) and those not receiving OMT (RR 0.21, 95% CI 0.08 – 0.58; Panel D).

Conclusions:
In a contemporary cohort of patients enrolled in a trial of endovascular therapy for CLTI, the use of OMT was ~80%. Use of OMT was higher in those with risk factors and known CAD. The risk of adverse limb outcomes in the ANG group were lower with OMT than without OMT. The benefit of DRS vs. ANG was consistent regardless of OMT. Efforts to improve use of OMT in PAD are needed and a combined “pharmaco-invasive” approach to CLTI using optimal devices and OMT may improve outcomes.
Abstract 4139309: Rural-Urban Differences in Cardiovascular Mortality in the United States, 2010-2022
Authors: Marinacci Lucas , Zheng ZhaoNian , Wadhera Rishi
Published: November 2024

Background:
Between 2011-2017, US rural adults experienced higher cardiovascular (CV) death rates than their urban counterparts, and rural-urban disparities in CV mortality widened. Little is known about these trends have evolved in the wake of the pandemic. In this study, we provide an updated analysis of rural-urban differences in CV mortality.

Methods:
We used CDC WONDER to obtain national death data from 2010-2022. CV cause of death was identified by ICD-10 codes I00-99. Large metro, small/medium metro, and rural areas were defined using the National Center for Health Statistics Urban-Rural Classification. We calculated age-adjusted mortality rates (AAMRs) per 100,000 population and compared 2022 vs. 2010 using rate differences and two-sample t-tests. We then fit a Poisson regression model to estimate annual percent change (APC), evaluating trends from 2010-2019 and 2019-2022 due to reversal in CV mortality observed after 2019. We included an interaction term to assess differential trends by rurality, and repeated the analysis for younger (age 25-64) and older (age>64) adults.

Results:
Between 2010-2022, AAMRs were consistently highest in rural areas (
Figure 1, Table 1
). AAMRs increased in rural areas (rate difference [RD] +3.4 [95% CI 0.4, 6.4]) but declined in urban areas (RD -23.8 [-25.3, -22.2]). This significant differential change was driven by a rise in AAMRs among younger, rural adults (RD +23.2 [21.2, 25.1). In contrast, older adults experienced a decline in AAMRs, though this reduction was greater in urban vs. rural areas (
Table 2
).

From 2010-2019, overall APCs in AAMR decreased for all areas. However, when stratified by age, younger rural adults saw a significant increase (+1.0% [95% CI 0.5, 1.5]), while those in large metro areas did not (-0.2% [-0.5, 0.1]). Older adults saw a significant decrease across all areas.

Between 2019-2022, the overall APC in AAMR increased significantly in rural areas (+3.1% [0.4, 6]), but in not large metro areas (+1.2% [-0.4, 2.9]). CV mortality rose in most subgroups, but younger rural adults experienced the largest increase (+4.2% [1.3, 7.1]) (
Table 2
).

Conclusions:
Between 2010-2022, CV mortality increased in rural areas and decreased in urban areas. Younger, rural adults experienced the most pronounced rise in CV death, while older, urban adults experienced the steepest decline. These findings highlight an urgent need to address widening rural-urban disparities, particularly among younger adults.
Abstract 4139343: The Prevalence, Treatment, and Control of Cardiovascular Risk Factors Are Similar Among Medicare Advantage and Traditional Medicare Beneficiaries: A National Analysis
Authors: Oseran Andrew , Aggarwal Rahul , Wadhera Rishi
Published: November 2024

Background:
The federal government spends billions of dollars per year on payments to Medicare Advantage (MA) plans based largely on beneficiaries’ risk scores. Despite this, little is known about the true burden of cardiovascular risk factors among MA beneficiaries, or whether they receive better management of these conditions, compared to those in traditional Medicare (TM).

Goal:
To determine whether the prevalence of cardiovascular risk factors, as well as treatment and control rates, differ between MA and TM beneficiaries.

Methods:
We performed a cross-sectional analysis of adults
>
65 years enrolled in MA or TM participating in the National Health and Nutrition Examination Survey (2015-2018). We compared the prevalence of hypertension, obesity, hyperlipidemia, diabetes, and chronic kidney disease between MA and TM beneficiaries, and examined treatment and control rates for hypertension, hyperlipidemia, and diabetes. All outcomes were age- and sex-adjusted.

Results:
The age- and sex-adjusted prevalence of hypertension (67.8% vs 67.4%, OR 0.96 [95% CI 0.72, 1.26]), obesity (40.8% vs 40.7%, OR 1.02 [95% CI 0.81, 1.29]), hyperlipidemia (75.8% vs 76.2%, OR 0.96 [95% CI 0.75, 1.22]), and chronic kidney disease (19.9% vs 22.2%, OR 0.80 [95% CI 0.55, -1.16], p=0.25) were similar between MA and TM beneficiaries, while the prevalence of diabetes was higher in MA (31.5% vs 24.2%, OR 1.48 [95% CI 1.21, 1.80]). Adjusted rates of hypertension treatment (82.3% vs 79.1%, OR 1.25 [95% CI 0.94, 1.65], p=0.14) and control (53.3% vs 58.7%, OR 0.86 [95% CI 0.62, 1.20], p=0.38), hyperlipidemia treatment (56.4% vs 56.0%, OR 1.02 [95% CI 0.79, 1.32], p=0.87) and control (82.0% vs 74.9%, OR 1.63 [95% CI 1.02, 2.61], p=0.051), as well as diabetes treatment (76.3% vs 82.5%, OR 0.73 [95% CI 0.45, 1.20], p=0.23) and control (53.3% vs 55.1%, OR 0.88 [95% CI 0.57, 1.36], p=0.56) were all similar between these groups.

Conclusions:
In this nationally representative study using physical examination, biometric, and laboratory data from NHANES, the prevalence of common cardiovascular risk factors was similar between MA and TM beneficiaries. There were no differences in treatment or control rates for hypertension, hyperlipidemia, and diabetes.
Abstract 4139360: Assessing the Impact of a Healthy Foods Center Program Has on Food Insecurity and Healthcare Outcomes: A Pilot Study
Authors: Drury-Gworek Charlotte , Galper Kathleen , Barrett Tyson , Shergill Amber , Cuevas Elizabeth , Ereditario Colleen
Published: November 2024

Rationale:
Food insecurity impacts millions of households in the United States and can be a strong predictor of poor mental and physical health, as well as avoidable chronic health conditions. Patients with food insecurity tend to have increased healthcare utilization and costs when compared to those without. To help alleviate this need, several healthy foods centers (HFCs) were established within a local hospital network to provide immediate food access to patients screening positive for food insecurity, as well as health-focused education on nutrition (e.g., impacts on HbA1C and cholesterol), budgeting, and meal preparation. We sought to conduct a preliminary examination to understand if the services provided by the HFCs were associated with improved healthcare utilization and costs, with an emphasis on utilization pertaining to cardiometabolic illness.

Methods:
We conducted a pilot retrospective review of the electronic medical records and claims data, for adult patients who were referred to HFCs between 2019 and 2023. Patients in the intervention (visited an HFC at least once) and control (referred but did not visit any HFC) groups needed at least 8 months of continuous enrollment (6 months baseline and ≥2 months following their first HFC visit or referral date) to assess outcomes. Difference-in-differences regression models were used to identify any changes in emergency department (ED) visits, total costs of care, and cardiometabolic disease-specific savings after controlling for baseline differences between groups.

Results:
Most patients were female (68%), white (65%), and single (39%), with an average age of 55 years. The intervention group averaged 4.8 visits to the HFC. The intervention group relative to the control group from baseline to follow-up saw average benefits of $579 in unadjusted ED costs and $2040 in unadjusted total costs. Effect sizes trended towards savings, though not initially statistically significant following covariate adjustment. Savings within the sample varied by overall medical complexity, with the highest benefits seen among those managing multiple chronic illnesses; savings were also higher when evaluating disease-specific spend.

Conclusions:
Results of this pilot study for patients referred and seen in the HFC compared to the patients referred and not seen, suggest improvements in ED and total costs may be present with healthy food center interventions, with the greatest benefit among the sickest of the population.