bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11184: Effects of Supervised Exercise on Select Outcomes for Patients With Heart Failure
Authors: Roberts Kirsten
Published: April 2024

EFFECTS OF SUPERVISED EXERCISE ON SELECT OUTCOMES FOR PATIENTS WITH HEART FAILURE Background:
There is an urgent need to implement strategies to improve outcomes for heart failure (HF) patients. Supervised exercise programs are a Class A recommendation for a multitude of cardiac conditions and are reimbursable by Medicare and most insurance carriers. Stating lack of evidence of improved patient outcomes, the Centers for Medicare and Medicaid Services deny/limit HF as a reimbursable diagnosis for such programs.

Hypothesis:
To determine the impact of a supervised exercise program for HF patients on the functional capacity, quality of life, level of depression, and rate of hospital readmission.

Methods:
A before-after cohort study of HF patients who participated in an outpatient phase II cardiac rehabilitation program was done. HF patients (n = 70) with stable New York Heart Association class II-IV diastolic or systolic heart failure were enrolled during an outpatient nurse navigation contact or referral by cardiologists. Surveys to assess quality of life and level of depression (the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Patient Health Questionnaire-9 (PHQ-9)) were used. Functional level was measured using the 6 Minute Walk Distance (6MWD) test. Readmission data were collected from medical records.

Results:
Depression (PHQ-9) scores dropped (t = 5.86, p < .01). Quality of life scores (KCCQ) improved with for all KCCQ subsets (except system stability) including physical limitation (t = -7.86, p < .01), system frequency (t = -5.91, p < .01), system burden (t = -5.95, p < .01), total system (t = -6.62, p < .01), self-efficacy (t = -5.04, p < .01), quality of life (t = -7.35, p < .01), social limitation (t = -5.66, p < .01), overall summary (t value = -7.73, p < .01), and clinical summary (t value = -7.67, p < .01). Functional status improved with increase in 6MWD (t = -8.55, p < .01). Readmission rates improved with admission encounters dropping (t = 6.07, p < .01) and fewer number of days hospitalized (t = 4.96, p < .01).

Conclusions:
Participation in a supervised exercise program resulted in clinically and statistically significant positive changes in depression scores, quality of life scores, functional status, and rates of readmission.
Abstract 11205: Tropoelastin Inhibits Intimal Hyperplasia of Mouse Bioresorbable Arterial Vascular Grafts
Authors: Sugiura Tadahisa , Agarwal Riddhima , Yi Tai , Lee Yong-Ung , Tara Shuhei , Breuer Christopher K , Weiss Anthony S , Shinoka Toshiharu
Published: April 2024

Introduction:
Neointimal hyperplasia, which results from the activation, proliferation and migration of vascular smooth muscle cells (SMCs), is a detrimental condition for vascular stents or vascular grafts that leads to stenosis. Preventing neointimal hyperplasia is critically important for the success of arterial vascular grafts.

Hypothesis:
We assessed the hypothesis that tropoelastin seeding will prevent SMC proliferation and neointimal hyperplasia in bioresorbable arterial vascular grafts.

Methods:
Poly (glycolic acid) (PGA) fiber mesh coated with poly (l-lactic-co-
ε
-caprolactone) (PLCL) scaffolds reinforced by poly (l-lactic acid) (PLA) nano-fibers were prepared as bioresorbable arterial grafts. Tropoelastin was then seeded onto the luminal surfaces of the grafts. Female C57BL/6 mice were randomly divided into 2 groups: 1. Tropoelastin seeded group (n=10), and 2. Unseeded group (n=10). The grafts were implanted as infra-renal aortic interposition conduits. Animals were followed for 8 weeks then sacrificed to evaluate neotissue formation.

Results:
Tropoelastin treatment substantially reduced the number of cells that stained positive for SMC (α-SMA) and Proliferating cell nuclear antigen (PCNA) in the vessel walls (Unseeded group: 60 ± 36/HPF vs. Tropoelastin seeded group: 21 ± 13/HPF,
P
=0.048, Unseeded group: 11.0 ± 5.6 /HPF vs. Tropoelastin seeded group: 4.8 ± 1.7/HPF,
P
=0.043, SMC and PCNA, respectively, HPF; high power field) (Fig. A, B). Tropoelastin significantly reduced the thickness of the intimal layer (Unseeded group: 91 ± 22 μm vs. Tropoelastin seeded group: 50 ± 11 μm,
P
=0.004) (Fig. C).

Conclusions:
Tropoelastin seeding is beneficial in preventing SMC proliferation and neointimal hyperplasia in bioresorbable arterial vascular grafts.
Abstract 11217: Association of Hepatitis C infection and Incident Atrial Fibrillation
Authors: Bhave Prashant , Kabra Rajesh , Vaughan Sarrazin Mary
Published: April 2024

Introduction:
Prior studies have shown that HIV infection is associated with incident atrial fibrillation (AF). Anecdotal evidence suggests that patients with Hepatitis C virus (HCV) infection may also be at increased risk of AF at a young age.

Hypothesis:
We postulate that HCV infection increases the risk of incident AF.

Methods:
We performed a case-control study using administration data from the Veterans Health Administration. ‘Case’ patients included 103876 VA patients newly diagnosed with HCV during 2005-2013; patients with no use of VA services during the year prior to HCV diagnosis and patients with pre-existing AF were excluded. Each ‘case’ patient was matched to a single patient without HCV or AF. Patients were matched by age, race, gender, prior use of VA services, hypertension, sleep apnea, and other AF risk factors. Cox proportional hazards regression was used to define the association between HCV infection and incident AF.

Results:
The HCV and control groups were well matched by demographics and co-morbidities. The average follow-up period was 4.3 years. Among patients with HCV, 4087 (3.9%) patients were diagnosed with incident AF; 3185 (3.1%) patients without HCV were diagnosed with incident AF. Overall, the rate of new AF diagnosis per 10 patient-years of follow-up was 9.7% and 6.8% for patients with and without HCV, respectively. In Cox proportional hazards regression models, the relative hazard of AF was 1.42 times higher (95% CI, 1.35-1.48; p<0.001) for patients with HCV compared to those without.

Conclusions:
HCV infection appears to be associated with an increased risk of developing AF. Possible mechanisms include chronic systemic inflammation associated with HCV infection or direct cardiotoxic effects of the virus. It is unknown whether the use of new curative medications to eradicate HCV will reduce the incident risk of AF in these patients.
Abstract 11242: Clopidogrel Improves Endothelial Function in Healthy Individuals With Heightened Platelet Aggregation
Authors: Salimi Shabnam , Lewis Joshua P , Yerges-Armstrong Laura , Mitchell Braxton D , O’Connell Jeffrey R , Shuldiner Alan R , Parsa Afshin
Published: April 2024

Introduction:
Platelet activation can lead to enhanced oxidative stress, inflammatory response and endothelial dysfunction. To quantify the effects of platelet inhibition on endothelial function, we assessed platelet activity of healthy individuals before and after clopidogrel administration and evaluated its effects on endothelial function.

Hypothesis:
We hypothesized that clopidogrel, by attenuating platelet activity, would result in enhanced endothelial function.

Methods:
Microcirculatory endothelial function was quantified by thermal hyperemia (TH) and post-occlusive reactive hyperemia (PORH) laser Doppler flowmetry (LDF) in 287 and 241 relatively healthy and homogenous Old Order Amish individuals, respectively. LDF and platelet aggregation measures were obtained at baseline and after 7 days of clopidogrel administration. Our primary outcome was percent change in post- versus pre-clopidogrel LDF measures.

Results:
Pre-clopidogrel TH-LDF and platelet aggregation were higher in women than men (p<0.001). Clopidogrel administration was associated with an approximately twofold higher percent change in TH-LDF, in subjects with high compared to low baseline platelet aggregation (39.4%±10.1 vs. 17.4%±5.6, p=0.03). Clopidogrel also increased absolute TH-LDF measures in individuals with high platelet aggregation (1757.2 ± 765.6 to 2153.8 ± 1054.5, p=0.03), with a more prominent effect in women (1909.4 ± 845.7 to 2518.1 ± 1047.9, p=0.001). There was no evidence that clopidogrel influenced PORH-LDF measures.

Conclusions:
The administration of clopidogrel, in healthy individuals with high baseline platelet aggregation, results in improved TH-induced microcirculatory endothelial function. These data suggest that clopidogrel may have a beneficial effect on microcirculatory endothelial function, presumably through anti-platelet activity, and may confer additional vascular benefits.
Abstract 11307: Interleukin-1β and Methylation of Apoptosis Associated Speck-Like Protein Containing a Caspase Recruitment Domain Are Associated With Aerobic Capacity in Heart Failure
Authors: Butts Brittany , Butler Javed , Dunbar Sandra B , Corwin Elizabeth J , Gary Rebecca A
Published: April 2024

Background:
Aerobic capacity, as measured by peak oxygen uptake (V˙O
2
), is one of the most powerful predictors of prognosis in heart failure (HF). Inflammation is a key factor contributing to alterations in aerobic capacity, and the interleukin (IL)-1 cytokine IL-1β is implicated in this process. The adaptor protein ASC (apoptosis associated speck-like protein containing a caspase recruitment domain) is necessary for inflammasome activation of IL-1β. ASC expression is controlled through epigenetic modification, and lower ASC methylation is associated with worse outcomes in HF.

Hypothesis:
Peak V˙O
2
will be positively related to ASC methylation and negatively related to IL-1β in persons with HF.

Methods:
This cross-sectional study examined the relationship between ASC methylation and the inflammatory cytokine IL-1β with peak V˙O
2
in 54 stable outpatients with HF. All participants were NYHA class II or III, not currently engaged in an exercise program, and physically able to complete a symptom limited modified Balke exercise treadmill test.

Results:
Participants were 59 ± 10 years of age, 52% female, and 59% African American. Mean peak V˙O
2
was 16.68 ± 4.7 ml/kg/min. Peak V˙O
2
was positively associated with mean percent ASC methylation (r=.47, p=.001) and negatively associated with IL-1β (r=-.38, p=.007). Multiple linear regression models controlling for left ventricular ejection fraction and gender demonstrated that peak V˙O2 increased by 2.30 ml/kg/min for every 1% increase in mean ASC methylation and decreased by 1.91 ml/kg/min for every 1 pg/mL increase in plasma IL-1β.

Conclusions:
Mean percent ASC methylation and plasma IL-1β levels are associated with clinically meaningful changes in peak V˙O
2
in persons with HF. Inflammasome activation may play a mechanistic role in determining aerobic capacity. ASC methylation is a potentially modifiable mechanism for reducing the inflammatory response, thereby improving aerobic capacity in HF. Modification of ASC expression via behavioral interventions that increase ASC methylation may improve aerobic capacity in persons with HF.
Abstract 11335: Therapeutic Hypothermia Improves Cardiac Function After Successful Resuscitation From Cardiac Arrest in a Rat Model of Myocardial Infarction
Authors: Li Hao , Park Jeonghyun , Wen Yinlun , Song Fengqing , Wu Xiaobo , Wang Wei , Hua Tianfeng , Peberdy Mary A , Ornato Joseph , Tang Wanchun
Published: April 2024

Introduction:
We previously demonstrated that hypothermia improves post-resuscitation myocardial function in cardiac arrest animal models without coronary artery disease. In the present study, we investigated the effects of therapeutic hypothermia on post resuscitation myocardial function in a more clinically relevant rat model of myocardial infarction.

Hypothesis:
The therapeutic hypothermia improves post-resuscitation myocardial function after cardiac arrest and cardiopulmonary resuscitation in a rat model of myocardial infarction.

Methods:
Myocardial infarction was produced by left coronary artery (LCA) ligation 90 min prior to induction of ventricular fibrillation (VF). CPR with mechanical ventilation and precordial compression was initiated after 6 min of untreated VF. Defibrillation was attempted after 8 min of CPR. Animals were randomized into 2 groups: (1) Myocardial infarction-Normothermia group (MI-NT group, n=6), the core temperature was maintained at 37.0±0.2°C during resuscitation and next 4 hours after resuscitation; (2) Myocardial infarction-Hypothermia group (MI-HT group, n=6), the core temperature was maintained at 32.0±0.5°C during resuscitation and next 4 hours after resuscitation.

Results:
All animals were resuscitated successfully. Post-resuscitation ejection fraction (EF) and cardiac output (CO) were significantly greater in animals treated with hypothermia. (
p
<0.01, Figure 1 and 2).

Conclusions:
Therapeutic hypothermia significantly reduces the severity of post-resuscitation myocardial systolic dysfunction in a rat model of myocardial infarction.
Abstract 11654: Surgical Versus Medical Therapy for Prosthetic Valve Endocarditis: A Systematic Review and Meta-Analysis of 32 Studies
Authors: Mihos Christos G , Capoulade Romain , Yucel Evin , Picard Michael H , Santana Orlando
Published: April 2024

Background:
Prosthetic valve endocarditis (PVE) after valve replacement surgery is associated with significant morbidity and mortality. Whether a surgical or medical treatment strategy is preferable has not been clearly defined.

Methods:
A systematic review was performed to identify studies that compared re-operative valve surgery versus medical therapy for PVE. A meta-analysis was conducted on the outcomes of 30-day mortality, and follow-up survival and recurrent PVE. Risk ratios (RR) and 95% confidence intervals (CI) were calculated utilizing the Mantel-Haenszel method under a fixed or random effects model, as appropriate. Continuous and categorical variables were compared utilizing an independent t-test and a chi-square or Fisher’s exact test, respectively.

Results:
A total of 32 studies were identified, which included 2636 patients (Surgery=1320, Medical=1316), with a mean follow-up of 22 months (range 3-120). Patients undergoing valve reoperation were younger (58 ± 20 years versus 63 ± 22 years, p<0.0001), with a higher incidence of heart failure (38% versus 28%, p=0.0001) and paravalvular complications (paravalvular leak, prosthetic valve dehiscence, and/or paravavular abscess; 43% versus 19%, p<0.0001), while patients treated with medical therapy alone experienced more Staphylcoccus aureus PVE (32% versus 24%, p=0.0003). When compared with medical therapy, a valve reoperation was associated with a lower risk of 30-day mortality (25% versus 34%; RR 0.73, 95% CI 0.64-0.82, p<0.00001), and a greater survival at follow-up (69% versus 58%; RR 1.27, 95% CI 1.05-1.53, p=0.01), which was driven by the 15 studies published in the year 2000 or later. In patients with left-sided PVE, valve reoperation was also associated with a lower risk of 30-day mortality (25% versus 33%; RR 0.74, 95% CI 0.64-0.86, p<0.0001), and a greater survival at follow-up (71% versus 58%; RR 1.35, 95% CI 1.05-1.73, p=0.02), as compared with medical therapy. There was no difference in the incidence of recurrent PVE with regard to surgical versus medical therapy.

Conclusions:
Compared with medical therapy, reoperative valve surgery results in lower 30-day mortality and a greater survival at follow-up, and may be preferable for patients with PVE.
Abstract 11804: GsMTx4-D is a Cardioprotectant Against Myocardial Infarction During Ischemia and Reperfusion
Authors: Wang Jinli , Ma Yina , Sachs Frederick , Suchyna Thomas , Li Ji
Published: April 2024

Introduction:
GsMTx4 is a selective inhibitor of cationic mechanosensitive ion channels (MSCs) and has helped establish the role of MSCs in cardiac physiology. Inhomogeneous local mechanical stresses due to hypercontracture and swelling, likely induce elevated MSC activity that can contribute to the cation imbalance observed during ischemic reperfusion injury. This study was to determine if the D enantiomer of GsMTx4 can act as a cardioprotectant during ischemia and reperfusion and to evaluate its effects on cation influx and inflammatory kinases that are regulated by this influx.

Hypothesis:
GsMTx4 protects heart from ischemic insults through inhibiting the cationic mechanosensitive ion channels.

Methods:
Ischemia and reperfusion in the mouse heart involved ligating a coronary artery followed by release of the ligature.

Results:
GsMTx4-D was administered by acute intravenous injection during the ischemic event. Based on pharmacokinetic studies, GsMTx4-D dosage was set to achieve expected plasma concentrations between 50-5000 nM and heart tissue concentrations between 1-200 nM. Relative to vehicle injected animals, GsMTx4-D reduced infarct area by ~40% for acute and pretreated animals, and for both 20 and 45 min ischemic challenges. Many indicators of cardiac output were indistinguishable from sham-treated control hearts after GsMTx4-D treatment and most showed improvement at both 4 and 48 hrs post ischemia. Premature ventricular beats immediately following reperfusion were also significantly reduced by intravenous injections of GsMTx4-D. Myocytes cultured under hypoxic conditions treated with 10 μM GsMTx4-D showed improved contractility and near normal contraction-related Ca
2+
influx. GsMTx4-D inhibited indicators of ischemic damage such as the apoptotic signaling system JNK/c-Jun, but also inhibited the energy response signaling system Akt kinase.

Conclusions:
GsMTx4-D is a potent cardioprotectant that decreases infarct area, increases cardiac output and decreases arrhythmias that are caused by ischemia and reperfusion. GsMTx4-D improved cardiomyocyte function and suppresses apoptosis, making it potentially useful in multidrug strategies to treat ischemic heart disease.
Abstract 11833: Cost-Effectiveness Analysis of the Polypill Approach vs Periodic Risk Assessment for Prevention of Cardiovascular Disease
Authors: Ferket Bart S , Hunink Myriam , Khanji Mohammed , Agarwal Isha , Fleischmann Kirsten E , Petersen Steffen E
Published: April 2024

Introduction:
There is an international trend towards recommending medication to prevent cardiovascular disease (CVD) in individuals at increasingly lower cardiovascular risk. We sought to assess the cost-effectiveness of a population approach with a Polypill including statin and antihypertensives and periodic risk assessment with different risk thresholds.

Methods:
We developed a microsimulation model for lifetime predictions of CVD events, diabetes, and death in 259,146 asymptomatic UK Biobank participants aged 40 to 69, who attended 2006-2010 baseline visits. We assessed incremental costs and quality-adjusted life-years (QALYs) for Polypill scenarios differing for starting age, and periodic risk assessment with 10-year CVD risk thresholds of 10% and 20%. Analyses were undertaken from a UK health service perspective.

Results:
Restrictive risk assessment, in which statins and antihypertensives were prescribed when risk exceeded 20% (
Old guidelines
), was the optimal strategy gaining 123 QALYs (95% CI -173 to 387) per 10,000 individuals at an extra cost of £1.45 million (95% CI 0.89 to 1.94) as compared with current practice with an incremental cost effectiveness ratio of £11,797/QALY (see
Figure
). Although less restrictive risk assessment and Polypill scenarios prevented more CVD events and attained larger survival gains, these benefits were offset by the additional costs and disutility of daily medication use. Lowering the risk threshold for prescription of statins to 10% (
Current guidelines
) was economically unattractive, costing £40K per QALY gained. Starting the Polypill from age 60 onwards became the most cost-effective scenario when annual drug prices were to be reduced below £240. All Polypill scenarios would save costs at prices below £50.

Conclusions:
Periodic risk assessment using lower risk thresholds is unlikely to be cost-effective. A population approach with the Polypill would become cost-effective if drug prices were to be reduced.
Abstract 11839: Comparisons of Cardiopulmonary Exercise Testing Between Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction
Authors: Sato Takamasa , Kanno Yuki , Yoshihisa Akiomi , Takeishi Yasuchika
Published: April 2024

Background:
Parameters derived from cardiopulmonary exercise testing (CPET) are important prognostic markers, especially peak oxygen consumption (VO
2
), the minute ventilation carbon dioxide production slope (VE/VCO
2
slope), exertional oscillatory ventilation (EOV) and oxygen uptake efficiency slope (OUES) in chronic heart failure (CHF). However, the significance of these parameters has not been examined in terms of left ventricular ejection fraction (EF). We aimed to compare the impacts of these exercise parameters on clinical outcomes between CHF patients with reduced EF (HFrEF) and preserved EF (HFpEF).

Methods:
We analyzed 1190 patients (969 males, mean age 61.0 years) with CHF who admitted to our hospital and performed CPET. We divided subjects into two groups: HFrEF (LVEF<45%, n=655) and HFpEF (LVEF≥45%, n=535). We compared the independent factors to predict adverse composite cardiac events (cardiac deaths and rehospitalization due to worsening heart failure), cardiac deaths and all-cause deaths between HFrHF and HFpEF.

Results:
In the follow-up period (mean 1155 days), 407 adverse cardiac events (rehospitalization due to worsening heart failure and cardiac deaths), 172 cardiac deaths and 247 all-cause deaths were occurred. Kaplan-Meier analyses demonstrated that composite cardiac event rates, cardiac and all-cause mortalities were significantly higher in HFrEF than in HFpEF (P<0.001, respectively). In Cox proportional hazard multivariate analyses, independent predictors of composite adverse events were peak VO
2
, VE/VCO
2
slope and OUES in HFrEF (P<0.001, P<0.001 and P=0.001, respectively), those of cardiac deaths were peak VO
2
, OUES and VE/VO
2
slope (P=0.002, P=0.005 and P=0.008, respectively), and those of all-cause deaths were peak VO
2
, OUES and VE/VCO
2
slope (P=0.001 and P=0.023 and P=0.041, respectively) in HFrEF. On the other hands, the independent predictors of composite adverse events were peak VO2 and VE/VCO2 slope (P<0.001 and P=0.041), and those of cardiac deaths and all cause deaths were peak VO
2
in HFpEF (P<0.001 and P=0.001, respectively).

Conclusion:
Impacts of these parameters were different between HFrEF and HFpEF based on several clinical outcomes.
Abstract 11921: Risk Stratification for Ventricular Arrhythmia in Patients With Repaired Tetralogy of Fallot (TOF) via Image-Based Computational Simulations: A Pilot Study
Authors: Cartoski Mark J , Prakosa Adityo , Nikolov Plamen , Boyle Patrick M , Spevak Philip J , Trayanova Natalia
Published: April 2024

Introduction:
Patients with repaired TOF have increased arrhythmia risk due to myocardial fibrosis, scar and right ventricular dilation. Current risk stratification lacks consistent predictive value and clinical practicality. We surmised that personalized models developed from cardiac late gadolinium enhancement MRI (LGE-MRI) could correctly assess risk of arrhythmia in patients with repaired TOF using our previously-validated Virtual Arrhythmia Risk Prediction (VARP) protocol.

Methods:
As a proof-of-concept retrospective study, we developed personalized 3D computational models of TOF hearts from LGE-MRI scans. Three patients with clinically disparate arrhythmia status were included: patient 1 (P1) had clinical episodes of sustained ventricular tachycardia (VT) and inducibility in electrophysiologic study (EPS); patient 2 (P2) had negative EPS despite documented runs of non-sustained VT; patient 3 (P3) had no clinical evidence of VT. Then, for each heart, we applied our VARP protocol to generate a computational model, including personalized representations of scar and fibrosis. We then assessed the inducibility of reentrant arrhythmia from 26 pacing sites.

Results:
For all three cases, VARP outcomes correlated with clinical observations. In the P1 model sustained VT was induced with rapid ventricular pacing, while only non-sustained VT was induced in the P2 model (Fig 1). No arrhythmia was induced in the P3 model. Reentrant wavefronts in P1 and P2 occurred near the right ventricular outflow tract (RVOT) or ventricular septal defect patch, common sites of reentry observed in EPS in patients with TOF (Fig 1).

Conclusion:
Application of the VARP approach in repaired TOF patients is feasible and has the potential to correctly identify patients with a high risk of developing arrhythmia. With additional validation this non-invasive technique could serve as an effective tool for longitudinal risk assessment and help guide clinical decision making.
Abstract 12024: Changes in Respiratory System Static Compliance After Resuscitation in a Porcine Model of Prolonged Cardiac Arrest
Authors: Zheng Houzhen , Chen Rui , Yang Zhengfei , Wen Cai , Zhai Xiaozhu , Yu Tao , Peberdy Mary A , Ornato Joseph P , Tang Wanchun
Published: April 2024

Introduction:
Acute lung injury happens commonly after resuscitation due to ischemia reperfusion injury and complications of cardiopulmonary resuscitation (CPR). The static compliance of the respiratory system (Csrs) is a reliable indicator of lung injury, together with chest-wall compliance (Cscw) and lung compliance (Csl). In the present study, we investigated the changes in Csrs, Cscw and Csl after resuscitationin a porcine mode of prolonged cardiac arrest (CA).

Hypothesis:
Both Csrs and Csl are decreased after prolonged CA and CPR without significant changes in Cscw.

Methods:
Ventricular fibrillation was electrically induced and left untreated for 10 mins in six male domestic pigs weighing 39±3 kg. Defibrillation was then attempted by a single 150 J shock after 4 min of CPR. All the animals were resuscitated successfully. Succinylcholine chloride (1.0mg/kg) was given intravenously to relax the respiratory muscles and static pressure-volume (P-V) curves were obtained by constant low-flow method at baseline, 1, 2 and 8h after resuscitation. Airway opening pressure, esophageal pressure, transpulmonary pressure and tidal volume were assessed. Csrs, Cscw and Csl were calculated as the slope rates of the liner portion of the corresponding P-V curves.

Results:
Significant decreases in both Csrs and Csl were observed after resuscitation when compared with baseline (Figure). However, Cscw increased slightly at 1 h after resuscitation and returned to baseline 2 h post-resuscitation.

Conclusion:
Both Csrs and Csl were reduced significantly following resuscitation without significant changes of Cscw in a porcine model of prolonged CA and CPR.
Abstract 12104: Asymptomatic Acute Complications of Atrial Fibrillation Ablation Using Irrigated Radiofrequency Technology
Authors: Deneke Thomas
Published: April 2024

Introduction:
Complications after atrial fibrillation (AF) ablation are rare and therefore consequent analysis of risk factors is often hard. Although, in asymptomatic patients silent cerebral events (SCE) in magnetic resonance imaging (MRI) and endoscopically detected esophageal thermal lesions (EDEL) have been documented in a much higher percentage of these patients. These asymptomatic complications may serve as surrogate indicators for the potential for severe complications.

Hypothesis:
We evaluated the incidence of SCE and EDEL in patients undergoing AF ablation using irrigated radiofrequency ablation technologies.

Methods:
Overall 375 pts undergoing either single-tip contact-force irrigated RF ablation (N=231) or multipolar irrigated RF (nMARQ, N= 170). EDEL using post-ablation endoscopy (days 1 - 4) and SCE using diffusion-weighted brain MRI (days 1 - 3) were documented and related to procedural and patient-specific parameters. No symptomatic complications occurred in this patient cohort.

Results:
327 pts underwent post-ablation endoscopic evaluation for EDEL and 335 post-ablation MRI to detect SCE. Overall incidence of EDEL was 16% (53) including 4.5% (15) esophageal ulcers and 21% (72) had SCE. In the single-tip RF ablations 12% had EDEL and 20% SCE whereas in the nMARQ ablations 21% had EDEL and 23% SCE. The incidence of EDEL was higher in patients undergoing esophageal temperature monitoring using a thermal esophagus probe with non-insulated large metal electrodes (30% versus 6% in single tip and 31% versus 6% in nMARQ ablations). The use of this specific probe was the only independent predictor of EDEL. The incidence of SCE was relevantly lower in patients ablated under continuous oral anticoagulation (12% versus 37% for single tip and 15%versus 31% for nMARQ ablations).

Conclusions:
AF ablation using irrigated RF involves a risk of asymptomatic complications to the esophagus and brain relevantly higher than symptomatic complications. Reduction of asymptomatic complications may warrant beneficial effects on the most severe complications of AF ablation like periprocedural stroke and atrio-esophageal fistula.
Abstract 12141: ApoE-HDL Cholesterol Predicts Incident Cardiovascular Events: Aric Study
Authors: Agarwala Anandita , Sun Wensheng , Nambi Vijay , Guild Cameron , Coresh Josef , Ballantyne Christie M , Hoogeveen Ron
Published: April 2024

Background:
ApoE-HDL-C, a subfraction of HDL-C that contains ApoE, is thought to be cardioprotective via its inhibition of arterial stiffening and its role in reverse cholesterol transport.

Objective:
We examined the relationship between ApoE- HDL-C and incident cardiovascular events in the biracial Atherosclerosis Risk in Communities (ARIC) study.

Methods:
ApoE-HDL-C was measured in 9,258 ARIC participants using a novel automated homogeneous assay (Denka Seiken). The association between ApoE-HDL-C and HDL-C with incident cardiovascular events was assessed using Cox proportional hazard regression models. Covariates included age, race, gender, race, BMI, systolic blood pressure, use of anti-hypertensive medications, diabetes, smoking status, total cholesterol and triglycerides.

Results:
Mean ApoE-HDL-C and HDL-C levels were 5.06 ± 1.79 mg/dL and 51.10 ± 16.74 mg/dL, respectively. ApoE-HDL-C comprised roughly 10% of total HDL-C levels. ApoE-HDL-C levels were higher in non-diabetics, women and African Americans and showed strong positive correlations with HDL-C and total cholesterol levels. Both apoE-HDL-C and HDL-C were associated with incident CVD, driven mainly by CHD (Table 1). Each 10 mg/dL increase in HDL-C levels was associated with a decreased risk of incident CVD after multivariate adjustment (HR 0.89, 95% CI 0.85, 0.93, p<0.001). A 1 mg/dL increase in ApoE-HDL-C was associated with a decreased risk of incident CVD after similar multivariate adjustment (HR 0.91, 95% CI 0.88, 0.95, p<0.001).

Conclusion:
ApoE-HDL-C predicts incident CVD similarly to HDL-C in the biracial ARIC cohort.
Abstract 12202: New York Heart Association Class and the Mortality Benefit From Primary Prevention Implantable Cardioverter Defibrillator Use: A Pooled Analysis of 4 Randomized Control Trials
Authors: Friedman Daniel J , Al-Khatib Sana M , Zeitler Emily P , Han JooYoon , Bardy Gust H , Bigger J. T , Buxton Alfred E , Moss Arthur J , Lee Kerry L , Steinman Richard , Dorian Paul , Hallstrom Alfred , Cappato Riccardo , Kadish Alan H , Kudenchuk Peter J , Mark Daniel B , Inoue Lurdes Y , Sanders Gillian D
Published: April 2024

Introduction:
Primary prevention implantable cardioverter defibrillators (ICDs) reduce all-cause mortality by reducing sudden cardiac death. There are conflicting data regarding whether patients with more advanced heart failure (HF) derive ICD benefit owing to the competing risk of death from pump failure.

Methods:
We performed a patient level data meta-analysis of 4 primary prevention ICD trials (MADIT-I, MADIT-II, DEFINITE, SCD-HeFT) to determine the effect of ICD use on all-cause mortality by NYHA class. We included ICD and control patients with EF ≤35%, NYHA II or III HF, and myocardial infarction ≥40 days prior to randomization. Bayesian-Weibull survival regression models were employed to assess the impact of the ICD on mortality among the study population and by NYHA class.

Results:
Of the 2,763 patients who met study criteria, 68% (n=1,867) were NYHA II and 52% (n=1,435) were randomized to an ICD. In a multivariable model including all study patients, the ICD reduced mortality [HR 0.65, 95% posterior credibility interval (PCI) 0.40-0.99]. The interaction between NYHA class and ICD use on mortality was significant (posterior probability of no interaction = 0.036). The unadjusted effect of the ICD on mortality by NYHA class is depicted in
Figures A&B.
In stratified multivariable models including an interaction term for the NYHA class and ICD therapy, the ICD reduced mortality among NYHA II (HR 0.55, 95% PCI 0.35-0.85) and there was a trend toward reduced mortality in NYHA III patients (HR 0.76, 95% PCI 0.48-1.24). Between trial differences in mortality rates were observed across the NYHA III control patients (
Figure C)
suggesting heterogeneous risk profiles.

Conclusions:
Primary prevention ICDs reduce mortality in NYHA II patients and trend towards reducing mortality in NYHA III patients. An improved understanding of the heterogeneous natural history of NYHA III patients may help improve patient selection for primary prevention ICDs in this important subgroup.
Abstract 12505: Prognostic Significance of Myocardial Extracellular Volume Fraction
Authors: Yang Eric Y , Ghosn Mohammad , Khan Mohammad A , Gramze Nickalaus L , Pickett Grant W , Pickett Stephen J , Green Patrick W , Brunner Gerd , Nabi Faisal , Chan Wenyaw , Nambi Vijay , Ballantyne Christie M , Shah Dipan J
Published: April 2024

Background:
Cardiac magnetic resonance (CMR) techniques permit quantification of cardiac extracellular volume fraction (ECV), inclusive of interstitial fibrosis. ECV and late gadolinium enhancement (LGE), suggestive of cardiac replacement fibrosis, have been independently linked with heart failure (HF) events. Non-coronary artery disease type LGE has not been excluded in ECV measures. We examined associations between ECV censored for LGE-involved segments, LGE presence, and HF events.

Methods:
Mid short axis T1 maps were divided into 6 cardiac segments, each classified as LGE absent or present. Global ECV was derived from T1 maps using the area-weighted average of only LGE-absent segments. ECV was considered elevated if measured >30%, the upper 95% bounds of a healthy group without known cardiac disease (n=28). Patients were divided into 4 groups based on presence of elevated ECV and of any LGE. Subsequent HF admission and any death were ascertained. Their relationship with ECV was examined separately and as a composite with Cox proportional hazard models.

Results:
Of 1,604 serial patients with T1 maps, 1,047 were eligible after exclusions and followed over a median 10.5 (interquartile range 5.4, 21.4) months. Patients with elevated ECV had an increased risk for death (hazard ratio [HR] 2.60, 95% confidence interval [CI] 1.78 to 3.79)), HF admissions (HR 1.97, 95% CI 1.48 to 2.61), and combined endpoint (HR 2.14, 95% CI 1.69 to 2.70) regardless of LGE presence (Table). After adjustments for covariates, the relationship persisted for death (HR 1.86, 95% CI 1.24 to 2.79), hospitalization (HR 1.54, 95% CI 1.13 to 2.10), and combined endpoints (HR 1.60, 95% CI 1.24 to 2.07).

Conclusion:
Extracellular volume fraction measures were associated with heart failure outcomes, despite censoring of replacement fibrosis segments and even among patients without any replacement fibrosis. ECV may have a synergistic role with replacement fibrosis in heart failure risk assessment.
Abstract 12627: Clinical Anticancer Agent, RRx-001, protects From Doxorubicin-Induced Cardiotoxicity
Authors: Oronsky Bryan , Scicinski Jan , Cabrales Pedro
Published: April 2024

Introduction:
Anthracycline (ANT) chemotherapy (e.g., doxorubicin or DOX) is associated with dose-dependent cardiac dysfunction, leading to congestive heart failure, and therefore has limited clinical use. The cardiotoxicity may manifest acutely and/or months or years after treatment. Current clinically used therapies include angiotensin-converting enzyme/angiotensin-receptor antagonists (ARB) which are cardioprotective against ANT toxicity.

Hypothesis:
Pre-treatment with the hypoxic nitric oxide generating anticancer agent, RRx-001, mitigates acute DOX-induced cardiotoxicity. Candesartan (ARB) was used as a positive control.

Methods:
24 BALB/c mice were randomized to prophylactic treatment with vehicle, RRx-001, candesartan or no-intervention control. Within each of the three intervention arms, mice received treatment with DOX. Murine pressure-volume (PV) analysis was performed with microconductance catheters to characterize the degree of cardiovascular dysfunction within each group. The following hemodynamic parameters were monitored: left ventricular systolic pressure (LVSP), heart rate, and maximal rate of increase of left ventricular pressure (±dP/dt max).

Results:
Five days after doxorubicin injection, untreated mice displayed significantly impaired systolic (LVSP, –27%; dP/dtmax, –25%; LVDP, + 33%; P < 0.05) and global (SV, –52%; EF-20%; SW-62.5%; HR, –18%; CO, –57%; MAP-30%; SVR+20% P < 0.05) LV function when compared with the untreated group. In contrast, RRx-001-treated mice showed improved variables of systolic (LVSP, +27%; dP/dtmax, +25%; LVDP, -33%; P < 0.05) and global (SV, +52%; EF+20%; SW+62.5%; HR, +18%; CO, +57%; MAP+30%; SVR-20% P < 0.05) LV function compared to untreated controls. RRx-001 treated mice demonstrated improved parameters of LV function compared to candesartan, though the differences were not significant.

Conclusions:
Similar to the positive control, candesartan, the cardiotoxic effects of DOX in mice were attenuated by the prophylactic administration of RRx-001. These results suggest that RRx-001, as a multifunctional anticancer agent, which sensitizes cancer cells to the cytotoxic effects of chemotherapy and radiation, with beneficial cardioprotective effects.
Abstract 12677: Serum FGF23 Level is Associated With Cardiac Abnormality Among Patients Without Chronic Kidney Disease Stages
Authors: Tanaka Suguru , Morita Hideaki , Takeda Yoshihiro , Fujita Shu-ichi , Sohmiya Koichi , Hoshiga Masaaki , Ishizaka Nobukazu
Published: April 2024

Background:
Several experimental studies have demonstrated that fibroblast growth factor 23 (FGF23) may induce myocardial hypertrophy. On the other hand, few studies have clearly demonstrated the relationship between FGF23 level and left ventricular hypertrophy among subjects without chronic kidney disease (CKD; i.e., CKD stage G1 or G2). We investigate the association between FGF23 and cardiac parameters among 903 patients with various degrees of renal function, including 234 patients with CKD stage G1/G2.

Methods and Results:
Serum levels of full-length FGF23 were determined by enzyme immunoassay. After adjustment for sex, age, and estimated glomerular filtration rate (eGFR), the highest FGF23 tertile was significantly associated with left ventricular hypertrophy among patients with CKD stage G1/G2 as compared with the lowest FGF23 tertile as well as among those with CKD stage G3a/G3b/G4. This association retained significance after further adjustment for serum levels of corrected calcium, inorganic phosphate, and C-reactive protein. FGF23 was also associated with left ventricular ejection fraction (LVEF) <50% among patients with CKD stage G1/G after multivariate analysis. By the ROC curve analysis among these no-CKD patients, compared with model 1 (combination of age, sex, and eGFR), area under the curve of model 2 (model 1+FGF23) was significantly greater for the prediction of left ventricular hypertrophy.

Conclusions:
An association between FGF23 and cardiac hypertrophy and systolic dysfunction was observed among patients without CKD as well as those with CKD, suggesting FGF23 per se may have direct effect on the cardiac geometry and performance.
Abstract 12824: Mortality Outcomes at 30 Days and 1 Year After Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction Due to Unprotected Left Main Coronary Artery Occlusion
Authors: Chen Ruth , Chan Siew P , Loh Poay H , Loh Joshua , Tay Edgar , Chan Mark , Lee Chi H , Low Adrian , Tan Huay C , Chan Koo H
Published: April 2024

Introduction:
Patients with acute myocardial infarction (AMI) due to unprotected left main coronary artery (ULMCA) occlusion are often critically ill at presentation. Emergency surgical revascularization is often associated with significant time delay and high mortality risk, as such, primary percutaneous coronary intervention (PCI) has been advocated as the preferred form of reperfusion therapy. Data on the clinical outcomes in this setting however remains limited.

Hypothesis:
We hypothesised that primary PCI is a feasible revascularization therapy in AMI due to ULMCA occlusion and the identification of the predictors of outcomes would aid in clinical decision-making.

Methods:
From 2005 to 2015, 71 patients with AMI due to ULMCA occlusion who underwent primary PCI had their outcomes evaluated retrospectively. Given the complex data interrelationships, a generalized structural equation model was applied for identifying the predictors of 30-day and 1-year mortality. All statistical analyses were conducted at 5% level of significance.

Results:
Majority of the patients (mean age 58.0 ±11.5, 90.1% male) had cardiogenic shock (64.7%) and cardiac arrest (70.1%) and 71.8% were intubated. Procedural success was achieved in 87.3% of patients. Mortality at 30-day was 59.1%, including 16.9% intra-procedural deaths. Cardiogenic shock (Adjusted odds ratio [AOR] 12.1), cardiac arrest (AOR 12.0) and intubation (AOR 282.0) were significantly associated with 30-day mortality. Additionally, a QRS duration of >130 milliseconds on the presenting electrocardiogram was also predictive of cardiogenic shock (AOR 4.5) and 30-day mortality (AOR 10.0). All-cause mortality at 1 year was 63.4% and for which QRS duration >130 milliseconds (AOR 25.4), cardiac arrest (AOR 8.8) and intubation (AOR 16.9) remained predictive of mortality but not cardiogenic shock (AOR 1.8, p >0.05).

Conclusion:
In conclusion, ULMCA occlusion is associated with a high incidence of 30-day mortality despite successful primary PCI. Patients presenting with a broad QRS complex, cardiogenic shock, cardiac arrest, or requiring intubation have a particularly poor prognosis. However, after thirty days, the mid-term survival rate of the remaining patients appeared favorable.
Abstract 12923: The Sustained Benefit of Short Term Treatment With Colchicine After Acute Myocardial Infarction
Authors: Fujisue Koichiro , Sugiyama Seigo , Sugamura Koichi , Kurokawa Hirofumi , Matsubara Junichi , Izumiya Yasuhiro , Kaikita Koichi , Hokimoto Seiji , Ogawa Hisao
Published: April 2024

Background:
In acute myocardial infarction (MI), acute inflammation and NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome are involved in cardiac damage, remodeling, and developing heart failure (HF). Several studies have reported that colchicine attenuated the infarct size and inflammation in MI. However, the sustained benefit of colchicine administration after MI on survival and cardiac function is unknown. We hypothesized that short-term treatment with colchicine could inhibit the cardiac inflammation and NLRP3 inflammasome, and improve survival and cardiac function during recovery phase of MI.

Methods:
Mice were induced MI by permanent ligation of the left anterior descending coronary artery. Mice randomly received 0.1 mg/kg/day colchicine or saline (control) orally from one hour to 7 days after MI.

Results:
Colchicine significantly improved survival rate compared with control at 4 weeks after MI (colchicine, n=48: 89.6% vs. vehicle, n=51: 70.6%, P<0.01). Colchicine significantly improved left ventricular end-diastolic diameter (5.0±0.2 vs. 5.6±0.2 mm, P<0.05) and ejection fraction (41.5±2.1 vs. 23.8±3.1%, P<0.001) assessed by echocardiogram, and HF-development as pulmonary edema assessed by lung weight at 4 weeks after MI (P<0.05). Histological analysis revealed that colchicine significantly inhibited the infiltration of Gr-1-positive granulocytes and Iba-1-positive macrophages in the infarct area at 24 hours after MI, and significantly improved left ventricular scar expansion at 1 week after MI. In the infarcted myocardium at 24 hours after MI, colchicine significantly attenuated the MI-induced myeloperoxydase activity and the mRNA expression of tissue necrosis factor-α, interleukin-1ß, monocyte chemoattractant protein-1, macrophage inflammatory protein-2, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and pro-caspase-1 compared with control.

Conclusions:
Short-term treatment with colchicine successfully attenuated the infiltration of inflammatory cells, cytokines, and NLRP3 inflammasome in the infarcted myocardium, leading to improvement of adverse cardiac remodeling, cardiac function, HF-development, and survival.
Abstract 12938: Circulating Long Noncoding RNAs Predicts Adverse Cardiovascular Outcomes in Patients With End-Stage Renal Disease
Authors: Shi Yin-Chun , Chen Yen-Ting , Lai Chun-Fu , Lin Chin-Hsien , Gu Jian , Chuang Kai-Wen , Lee Ying-Tung , Yang Kai-Chien
Published: April 2024

Introduction:
Cardiovascular (CV) disease is the major cause of death in uremic patients. Conventional risk factors fail to predict adverse CV outcomes with uremia. This study aimed to test the hypothesis that circulating long non-coding RNAs (lncRNA) can be a useful biomarker to predict CV events and death in uremic patients.

Methods:
Cell free, circulating lncRNA profiling was conducted using plasma RNA from end-stage renal disease (ESRD, n=33), chronic kidney disease (CKD, n=8) and healthy (n=19) subjects by RNA sequencing. Participants were followed up for 3 years for major adverse CV events (MACE: acute coronary syndrome, heart failure, stroke and CV death).

Results:
A total of 512 million sequencing reads were obtained from 60 plasma RNA samples. Among the 1897 lncRNAs detected in human plasma, 486 (363 up,123 down) and 41 (34 up, 7 down) were significantly dysregulated with ESRD and CKD, respectively. Hierarchical clustering analysis revealed that plasma lncRNA expression pattern discriminates ESRD and CKD from control samples. Pathway analysis of the dysregulated lncRNAs in ESRD based on their nearby mRNAs (cis-mRNA) showed significant enrichment of genes involved in unfolded protein response and fatty acyl-CoA biosynthesis, both of which have been implicated in the pathogenesis of uremia. Analysis on an independent microarray dataset obtained from renal biopsy samples of 48 patients with advanced kidney disease and 8 healthy subjects (GSE66494) revealed that ~15% (72 out of 486) of the dysregulated plasma lncRNA with ESRD are similarly dysregulated in diseased kidney tissues, suggesting that circulating lncRNA expression profiles can mirror, at least in part, the changes of lncRNA expression in diseased kidneys. During the follow-up period, 10 ESRD patients experienced MACE; 129 lncRNAs were differentially expressed in ESRD patients with MACE, compared to those without one. Among them, lncRNA FAM66D was a significant predictor of MACE (Hazard ratio 1.2, 95% CI 1.05-1.36,
P
=0.003) and could discriminate between ESRD patients with and without high risks for MACE (ROC curve AUC 0.92, 95% CI 0.76-1.00).

Conclusions:
Circulating lncRNAs reflect the disease states of uremia and could serve as a useful biomarker to predict the CV outcomes in uremic patients.