bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18484: Impaired Skeletal Muscle Efficiency and Power After Correction for Lean Muscle Mass in Patients With Advanced Heart Failure
Authors: Wu Christina , Dunlop Mark , Armstrong Hilary , Kato Tomoko S , Foreman Daniel , Bartels Matthew N , Schulze Paul Christian
Published: April 2024

Introduction:
Patients with advanced heart failure (HF) develop metabolic abnormalities leading to skeletal muscle wasting and changes in body composition that include lean skeletal muscle and adipose tissue.

Hypothesis:
We hypothesized that HF subjects have decreased skeletal muscle efficiency, work performance and muscle power compared to control subjects.

Methods:
Whole body dual-energy X-ray absorptiometry (DEXA) scanning for determination of total body mass, fat mass, % body fat, lean body mass was performed in 9 control subjects (age 51±8 yrs, EF 63.0±4.2 %, BMI 25.7±28.2 kg/m
2
, peak VO2 30.3±7.4 mL/kg/min) and 31 HF subjects (age 59±10 yrs, EF 27.9±7.8 %, BMI 28.2±4.7 kg/m
2
, peak VO2 15.3±3.8 mL/kg/min). Muscle function was assessed by isometric and isokinetic functional testing using the Biodex System 4 Pro of all extremities. Functional parameters were corrected for lean muscle mass determined by DEXA scanning.

Results:
Total fat mass and percentage body fat were higher in HF subjects (fat mass: 25.5±7.8 vs 16.4±4.8 kg in controls; p=0.002; % body fat: 31±7 vs 23±7 % in controls; p=0.006) without differences in any of the parameters of lean muscle mass. After correction for lean muscle mass, HF subjects showed decreased muscle power (0.32±0.15 vs 0.45±0.13 watts/kg in controls; p=0.02) and total muscle work (2.57±1.16 vs 3.58±0.94 J/kg in controls; p=0.02) in the lower extremities. Of note, no differences between HF and control subjects were found in the upper extremities.

Conclusion:
HF subjects have similar lean muscle mass compared to controls. Skeletal muscle power and work performance is significantly reduced in HF subjects even when normalized for lean muscle mass. These novel findings indicate the development of an intrinsic skeletal myopathy that is impairing muscle performance and likely contributes to increased fatigue and frailty in patients with advanced HF.
Abstract 18517: Cardiac BIN1 Folds T-Tubule Membrane to Control Ion Flux and Limit Arrhythmia
Authors: Hong Ting-Ting , Yang Huanghe , Zhang Shan-Shan , Bhargava Anamika , Grabe Michael , Gorelik Julia , Jan Lily , Shaw Robin
Published: April 2024

Cardiomyocyte T-tubules allow electrical stimuli to quickly reach the cell interior, triggering calcium transients and muscle contraction. Bridging Integrator 1 (BIN1), a membrane scaffolding protein associated with calcium channel trafficking to cardiac T-tubules, is down-regulated in failing hearts. Here we find that BIN1 also mediates dense folding within cardiac T-tubule invaginations. In mice, heterozygous cardiac specific Bin1 deletion does not affect cardiomyocyte morphology, but on microscopy (Figure 1) and electrophysiological studies, BIN1 knockout removes the T-tubule folds, increasing the rate of local extracellular calcium and potassium ion diffusion. Loss of folds also results in prolongation in cardiomyocyte action potential duration and spontaneous ventricular ectopy in intact animals. We find that the T-tubule folds are rescued by a particular BIN1 isoform, BIN1+13+17, which is specific for cardiac T-tubules, and non-existent in skeletal muscle. We found that BIN1+13+17 uses actin to stabilize cardiac T-tubule membrane at Z-discs, explaining how the folds can form. In conclusion, a cardiac BIN1 isoform recruits the actin cytoskeleton to fold T-tubule membrane, creating a fuzzy space that regulates ion flux and protects against arrhythmia. When BIN1 is decreased, such as in heart failure, arrhythmias can result.

Figure 1: TEM images at 150,000X magnification of individual T-tubule cross sections in WT and BIN1 HT mice. Note extra membrane in the WT T-tubule. Bottom panel contains intensity profiles of the two images.
Abstract 18522: Echocardiogram in the Evaluation of Patients With Syncope and Normal Electrocardiogram: Do We Need It
Authors: Atoui Moustapha , Gonzalez Christian , Bhandari Manoj , Rosdan Socrates , Peralta Richard , Nicu Marin , Bella Jonathan N , Sklyar Eduard
Published: April 2024

Background:
Syncope is a major cause for emergency room visits and hospital admissions. The electrocardiogram (ECG) serves as an important and cheap diagnostic tool, but most patients undergo additional cardiac testing including echocardiogram. However, little is known about its benefit in patients with normal ECG.

Hypothesis:
We hypothesize that patients with syncope and normal ECG are likely to have normal echocardiogram.

Methods:
We conducted a retrospective chart review of adult patients admitted with syncope between Jan 2011 and Mar 2012. Demographics and cardiac testing were reviewed. Patients with positive drug screen or who didn’t meet our syncope definition were excluded. Study population was divided into two groups based on ECG. Abnormal ECG includes any arrhythmia, conduction delay, chamber hypertrophy and ST/T abnormalities. Abnormal echocardiogram includes any wall motion abnormality, decreased ejection fraction, significant valvular disease, pulmonary hypertension or chamber enlargement. Descriptive statistics with Confidence intervals (CIs), interquartile ranges (IQRs; 25%, 75%) and linear regression were done using SPSS 20.

Results:
We identified 497 adult patients admitted with syncope. Only 198 met our inclusion criteria. Mean age was 58 years (25%, 75% IQR 48, 70), 40% Men, 50% Hispanics, 30% Black, 71% Hypertensive, 29% Diabetics, 13% with Coronary artery disease and 3% with congestive heart failure. Normal ECG group consists of 110 (56%; 95% CI: 49-63) patients. Echocardiogram was performed on 177 (89%; 95% CI: 85-94) patients, from them 16 (8%; 95% CI: 4 to 12) were abnormal and only 2 (2%; 95% CI: -1 to 4) were in patients with normal ECG. A correlation was found between the patients with normal ECG and normal Echocardiogram (P<0.001). On multiple linear regressions, predictors of abnormal echocardiogram were: Diabetes (β= - 0.145, p= 0.031), coronary artery disease (β= 4.32, p= <0.001), congestive heart failure (β= 0.147 p= 0.027), and abnormal ECG (β= 0.185, p= 0.006).

Conclusion:
In conclusion, a normal ECG correlates with a normal echocardiogram in patients presented with syncope. Echocardiogram, frequently performed, may not be needed in this specific group of patients.
Abstract 18607: High-Risk, Multi-Vessel Coronary Intervention Guided by Viability-Imaging and Supported by Awake-ECMO in Patients With Severe Ischemic Cardiomyopathy is Feasible, Safe, and Efficacious
Authors: Tongers Jörn , KÜhn Christian , Berding Georg , Bengel Frank , Ahrens Holger , Röntgen Philipp , Hupa Katharina , Hagl Christian , Haverich Axel , Bauersachs Johann , Schieffer Bernhard
Published: April 2024

Background:
The burden of end-stage coronary artery disease is rising and its care is complicated by cardiac failure and hospitalization. Recruitment of ischemic but viable myocardium is warranted to balance risk and benefit. Mechanical support enables high-risk coronary interventions despite severe LV-dysfunction. We aimed to develop a therapeutic algorithm of viability guided, awake-ECMO supported revascularization to stabilize therapy-refractory patients.

Methods/Results:
In this single-center study, consecutive patients (n=5, 61±9 yrs, all male) were prospectively enrolled (baseline: EF/echo study 15±4%; EF/SPECT-CT 17±5%). Myocardial perfusion SPECT-CT and viability 18-fluordesoxy-glucose (FDG)-PET imaging was performed. Veno-arterial ECMO (rate 3050±495 rpm, flow 2.8±1.0 l/min) was inserted in awake patients. Targeted by viability pattern, complex interventional revascularization was performed (2.8±1.1 vessels/patient, 3.0±1.5 stents/patient) without complications. Because no procedure/ECMO-related complications occurred, patients were discharged 5-7 days after PCI. During follow-up cardiac function improved significantly (ΔBNP: -42±15 %, p=ns; EF/echo: follow-up 26±7 %, ΔEF +11±7% vs. baseline, p<0.05; EF/SPECT-CT 29±7%, ΔEF +11±6% vs. baseline, p<0.05). This observation was associated with a clinical improvement (NYHA: 2.2±0.8; 6-minute walk: 242±76m; workload: max. 69±24W, VO
2
max. 9±2 ml/(min*kg), O
2
-pulse 8±2 ml/beat). Reflecting the recruitment of hibernating myocardium, perfusion defect score (SRS) was 27±15, LV-perfusion/metabolism mismatch 37±15%, and extent of scar 20±25%. Following revascularization, the perfusion defect score decreased (SRS: follow-up 21±14, p<0.05); 50 of 85 myocardial segments showed significant improvement. All patient reported freedom from acute events for 172±61 days.

Conclusion:
We developed a novel algorithm of high-risk, multi-vessel coronary intervention guided by perfusion/viability-imaging and supported by transient awake-ECMO in fragile patients. This interdisciplinary strategy was safe, feasible, and efficacious in recruiting hibernating myocardium, and improving formerly unstable patients.
Abstract 18626: A Novel Inhibitory Role of MicroRNA-1 in Cardiac Fibroblast Proliferation and Differentiation
Authors: King Michelle E , Zhang Peng
Published: April 2024

Fibroblasts play a key role in cardiac remodeling by differentiating into myofibroblasts, proliferating and producing excess extracellular matrix. MicroRNAs (miRs) are important regulators in cardiac development and disease. To date, miR analyses have been performed mostly in myocytes and cardiac tissue; little is known about miRs in cardiac fibroblasts. Using miR arrays, we determined the expression and regulation of miRs in adult rat ventricular fibroblasts in a culture model that mimics the phenotypic and functional changes of fibroblasts in diseased heart. Among miRs that were dynamically regulated, we found that miR-1, a muscle-enriched miR that has so far been extensively studied in myocytes, is expressed in fibroblasts and markedly downregulated (~10-fold) upon activation. MiR-1 downregulation was also observed in fibroblasts stimulated with angiotensin II or TGFβ for 48 hours. Gain-of-function studies in cultured rat ventricular fibroblasts showed a dose-dependent inhibitory effect of miR-1 on fibroblast proliferation (3- and 26-fold overexpression led to a 13% and 34% reduction, respectively). In contrast, fibroblast proliferation was significantly increased by 20% when endogenous miR-1 was only knocked down by 40%. Similar changes were observed in fibroblasts subjected to angiotensin II and TGFβ. Using immunostaining, we found a marked reduction of α-smooth muscle actin expression by miR-1, indicating an inhibitory effect of miR-1 on fibroblast differentiation. Mechanistic studies showed miR-1-dependent regulation of protein expression of several putative miR-1 targets that are involved in initiation of cell cycle progression (e.g., cyclin D2, CDK6) and fibrosis development (e.g., PKCε, HDAC4), some of which have been confirmed for miR-1 targeting by 3’-UTR luciferase reporter assays. Together, we show dynamic regulation of miRs in cardiac fibroblasts upon activation and demonstrate a novel inhibitory role of miR-1 in cardiac fibroblast proliferation and differentiation. Our data suggest a potential anti-fibrotic effect of miR-1 overexpression in fibroblasts and highlight the importance of cell type-specific miR-1 modulation, given the potential for arrhythmia induction reported for miR-1 overexpression in myocytes.
Abstract 18662: Frequency and Temporal Patterns of Implantable Cardiac Defibrillator Therapies in Patients With Left Ventricular Assist Devices
Authors: Appelbaum Jason , Weragoda Ramal , Lloyd Michael , Langberg Jonathan , Hoskins Michael
Published: April 2024

Background:
Left ventricular assist device (LVAD) use is becoming increasingly common in patients with end-stage heart failure. These patients are at high risk for ventricular arrhythmias. The pattern of ICD therapies in these patients is not well characterized.

Methods:
Our single-center retrospective cohort included 86 patients with ICDs and LVADs followed at Emory University Hospital. Data collected included frequency of ICD therapies, type of therapy (appropriate vs. inappropriate; shocks vs. anti-tachycardia pacing (ATP)), and time-course of therapies.

Results:
36 patients (42%) received ICD therapy during a mean follow-up period of 13.6 months. There were 105 episodes (2.9 episodes/patient) during which ICD therapies were delivered, with a total of 379 individual arrhythmias treated (3.6 arrhythmias per episode of therapy). 61.4% of therapies were appropriate, 8.4% were inappropriate, and 31.6% were unknown. Of the 79 episodes treated with appropriate therapy, 36 episodes (46%) required ICD shocks, whereas 43 episodes (54%) were treated with ATP alone. Overall, 33% of the total cohort and 81% of patients who received therapy received at least one ICD shock. Twenty-two patients (61%) received therapy between 1-3 times, while the remainder (14 patients, 39%) received therapy 3-10 times. Eighteen (17%) episodes occurred within the first month after LVAD implantation, with 10 (10%) occurring between 1-3 months, 53 (50%) occurring between 3-12 months, and 24 (23%) occurring more than one year after LVAD implantation.

Conclusion:
Analysis of our LVAD cohort revealed three important findings: 1. ICD therapy is very common (42%) in the first year after LVAD implantation; 2. Ventricular arrhythmias are highly clustered in this cohort; 3. ATP is frequently effective. These findings have important implications on device follow-up and programming for this expanding patient population.
Abstract 18663: Detection of Bacterial Device Infection of Cardiac Devices in a Rodent Model Using a Novel Pet Imaging Probe
Authors: Takemiya Kiyoko , Seo Wone Woo , Ning Xinghai , Weiss Daiana , Joseph Giji , Titterington Jane S , Nye Jonathon A , Murthy Niren , Goodman Mark M , Taylor W. Robert
Published: April 2024

Background:
Implantable cardiac devices improve prognosis and quality of life in cardiac patients, but there are problems that stem from device infection. There is often difficulty in making a definitive diagnosis of device infections. To this end, we have developed a new approach to specifically detect bacteria using a novel PET imaging probe. Maltohexaose is taken up by bacteria via the maltodextrin transport pathway and is internalized as a major source of glucose. Mammalian tissues do not possess this transporter. In this study, we evaluated whether maltohexaose labeled with fluorine-18 (F-18 FMH) is useful as a PET tracer to detect bacterial device infection in a rat model.

Methods and results:
We implanted surgical grade stainless steel device mock-ups in Sprague-Dawley rats. Methicillin sensitive Staphylococcus aureus (MSSA) in exponential growth phase was diluted to 1 X 10
6
CFU/ml. In the device infection group, rats were injected with 0.1ml (1 X 10
5
CFU) of MSSA around the mock-ups on post-operative day four. Two days later, rats were injected with F-18 FMH and were scanned with micro PET/CT. Infected devices showed a very avid uptake of tracer compared to the control (not infected) devices. The ratio of the signal in the region of interest (ROI) around the mock-up area and normal skin area was measured. The ratio of ROI in the device infection group was significantly increased compared to that in the control group that had the device but no injected bacteria. (2.34 ± 0.09 vs 1.79 ± 0.06, respectively. P<0.05, each n=4) In micro PET/CT imaging with the conventional tracer, fluorine-18-fluorodeoxyglucose, there was no significant change in the ratio of ROI between in the device infection group and in the control group. (2.21±0.12 vs 2.03±0.21, respectively. Each n=4)

Conclusion:
F-18 FMH shows great promise to be a potential tracer in PET imaging for the specific diagnosis of bacterial infections of implanted cardiovascular devices.
Abstract 18673: Human Enzyme Replacement Therapy in a Patient With Familial Lecithin Cholesterol Acyltransferase Deficiency: Rapid Appearance of Normal Appearing HDL
Authors: Shamburek Robert D , Freeman Lita , Sampson Maureen , Bakker-Arkema Rebecca , Krause Brian , Auerbach Bruce , Homan Ryan , Shamburek Alexandra , Schwartz Charles , Amar Marcelo , Remaley Alan
Published: April 2024

Introduction:
Lecithin cholesterol acyltransferase (LCAT) is a liver-derived enzyme in plasma that catalyzes the formation of cholesteryl esters (CE). Mutations in the human LCAT gene result in familial LCAT deficiency (FLD), characterized by absent high-density lipoprotein cholesterol (HDL-C), corneal opacities, anemia, and severe renal disease. Replacing the defective enzyme should restore the normal level of plasma CE (LCAT product) and lead to the appearance of alpha HDL (α-HDL) lipoproteins.

Aim:
To assess the formation of CE and the appearance of HDL over time in a FLD patient with recombinant human LCAT (ACP-501).

Methods:
A FLD subject with very low HDL-C (<5 mg/dL), corneal opacities, stage 4/5 renal disease, anemia, and splenomegaly received a 1 hour infusion of recombinant human LCAT (rhLCAT) and serial plasma samples were collected over 7 days.

Results:
HDL-C increased from <5 mg/dL to 17 mg/dL at 8 hours and remained measurable for 7 days. CE increased rapidly, doubling in concentration within 2 hours, and sustained a higher concentration than HDL over 7 days. An increase in LDL-C was delayed about 6 hours suggesting CETP transfer of CE from HDL to LDL. Small sized particles were rapidly converted to HDL2 and HDL3 sized particles on FPLC. Large α-HDL appeared on agarose electrophoresis within 30 minutes. ApoAI Western blot analysis confirmed the rapid generation of apoAI staining α-HDL. α-1, 2 and 3 particles rapidly appeared by 2-D gel electrophoresis. Filipin stained 1-D gels revealed large α particles that persisted for 7 days. α-4 sized particles decreased as α-HDL formed. Sudan stained 1-D gels showed the generation of CE-rich α-HDL.

Conclusions:
The infusion of rhLCAT (ACP-501) in a lecithin cholesterol acyltransferase deficient subject with no HDL rapidly generated CE and α-HDL with evidence of sustained activity over 7 days. CE appeared in LDL suggesting the transfer of CE from HDL to LDL by CETP. The lipid and lipoprotein changes are consistent with normal HDL maturation.
Abstract 18687: Obesity is Associated With Increased Mortality and Hospitalization in Patients Supported With a Continuous-Flow Left Ventricular Assist Device
Authors: Wehbe Ramsey M , Jensen Brian C , Chang Patricia P , Bowen Amanda , Waters Sarah B , Veeramachaneni Aparna , Sheridan Brett C , Katz Jason N
Published: April 2024

Background:
Greater body mass index (BMI) is associated with poor prognosis following cardiac transplantation, but little is known about the influence of BMI on outcomes after mechanical circulatory support (MCS). In particular, no data exists describing either serial changes in BMI or the impact of baseline obesity on morbidity or mortality in “real-world” patients supported with a continuous-flow LVAD (CF-LVAD).

Methods:
We reviewed records for all consecutive patients implanted with a CF-LVAD at our institution from 2008-2012. BMI was recorded prior to surgery, and at 1, 3, 6, and 12-months post-implant. Obesity was defined as a BMI ≥ 30 kg/m
2
. Serial BMI measurements were analyzed for significance, and Cox proportional hazards analysis was used to identify any associations between pre-implant BMI, or BMI changes, and survival or all-cause hospitalization.

Results:
Ninety-eight patients were included - 79 as bridge-to-transplant (BTT) and 19 as destination therapy (DT). Median follow-up was 256d, during which 24 patients died, 31 were transplanted, and 43 remained on MCS. At baseline, median BMI was 27.1 kg/m
2
(IQR 23.6, 30.9) and 27% were obese. Obesity rates were similar in BTT and DT cohorts. Non-obese patients exhibited a mean weight gain from pre-implant to 12 months of 11.7 ± 1.4 kg (p<0.001), while obese patients showed no significant changes in weight. Pre-implant obesity was associated with increased mortality at 90d (31% vs 6% non-obese, HR 6.0, p=0.002) and with decreased hospitalization-free survival (HR 1.7, p=0.04). Neither absolute nor relative changes in BMI after CF-LVAD were significantly associated with the evaluated outcomes.

Conclusions:
Obese patients have a significantly increased risk of death and hospitalization within the first 90d after the implantation of a durable CF-LVAD. This is the first study to demonstrate a mortality liability associated with obesity in patients implanted with these contemporary devices. Similar to clinical trial cohorts, non-obese patients gained a significant amount of weight during LVAD support, while obese patients neither gained nor lost weight. Serial changes in BMI did not influence outcomes. Future analysis will focus on mode of death and causes of morbidity for these obese patients.
Abstract 18698: Poor Quality of Life Impacts Successful Adoption and Completion of a Behavioral Weight Management Program for Overweight and Obese Patients With Heart Failure
Authors: Evangelista Lorraine , Motie Marjan
Published: April 2024

Background:
Clinical trials involving behavioral interventions for weight management in obese persons are often compromised by moderate levels of attrition. Previous studies have shown pretreatment variables (e.g. initial body weight, quality of life [QOL]) to be significantly related with successful completion of a behavioral weight management program, but is poorly understood in heart failure (HF) patients.

Objectives:
To assess personal and psychosocial differences between successful - defined as ability to complete a 3-month behavioral weight loss program - and unsuccessful participants in a RCT examining the effects of a high protein vs. standard protein diet on adiposity; and 2) identity predictors of program completion.

Methods:
Demographic and psychosocial assessments inclduing the Minnesota Living with Heart Failure Survey (higher score, worse QOL) were completed at baseline and 3 months. Comparisons were made between participants who completed the 3 month weight management program (n = 34) and participants who did not (n = 15).

Results:
Thirty four (70%) of the 49 participants - mean age 59.1 ± 9.8; weight 248.8 ± 29.7 lbs.; VO
2
max 12.5 ± 3.7 mg/kg/ml; 55% White; 20% Hispanics; 16% Blacks; 8% Asians - completed the weight management program. There were no age or gender differences between the two groups; Whites were less likely to complete the intervention compared to their counterparts (p = 0.47). There were statistically significant differences in QOL scores between completers and non-completers; overall QOL 40.8 ± 20.3 vs. 58.7 ± 24.2, p = 0.010; physical QOL 16.4 ± 9.3 vs. 24.7 ± 10.4, p = 0.008; emotional QOL 9.1 ± 7.0 vs. 14.5 ± 7.5, p = 0.020. After controlling for age, gender, race, initial weight, and functional status, QOL explained an additional 19% of the variance in successful completion of the weight management program.

Conclusion:
Personal and psychosocial variables may be useful as pretreatment predictors of success level and/or attrition in obese patients who participate in a RCT to test the effects of a behavioral weight management program. These factors can be used in developing readiness profiles for weight management, a potentially vital tool to address the issue of low success/completion rates in behavioral management of obesity.
Abstract 187: Code Team Members’ Perception of Family Presence During Cardiopulmonary Resuscitation at an Academic Medical Center
Authors: McCoy Jonathan , Bell Ginette , Hausman Kristen , Joiner Jennifer , Magarelli Karen , Mahoney Kathy , Maldanado Linda , Marqoux Kelly Keefe , Mastro Kari , Milloria Amy M , Tamburri Linda , Tortajada Dawn , Kathleen Zavotsky
Published: April 2024

INTRO:
Despite increased acceptance, barriers remain for family presence during cardiopulmonary resuscitation (CPR). Few have focused on the entire code response team. Our objective was to determine the perceived role of family presence, its benefit to patients and/or the code team, and barriers to implementation. We hypothesized that perceptions of family presence would vary by team member role.

Methods:
We conducted an IRB approved survey at an urban academic Level 1 trauma center during August, 2012. Subjects were members of the adult or pediatric code teams, including chaplains, clinical care techs (CCTs), registered nurses (RNs), advanced practice nurses (APNs), physicians, pharmacists, patient equipment techs, security officers, and respiratory therapists. A convenience sample was asked to complete an online family presence survey tool adapted with permission from Nykiel et al. Most responses used a five point likert scale ranging from strongly disagree (1) to strongly agree (5).

Results:
Five hundred eighty-eight of 3000 staff responded. They were 78% RNs and 25% adult critical care. Seventy percent had participated in family presence situations. More RNs, physicians, CCTs, and chaplains felt that family presence during CPR was part of their job (mean 4.1, 3.6, 3.6, 4.2 respectively) compared to respiratory therapists, pharmacists, security, and patient equipment techs (mean 2.2, 2.0, 1.5 respectively). Similarly, more RNs, physicians, CCTs, and chaplains felt comfortable providing emotional support to family members during CPR (mean 3.7, 4.1, 3.3, 4.2 respectively) compared to respiratory therapists, pharmacists, security, and patient equipment techs (mean 2.8, 1.9, 2.0, 1.8 respectively). Overall, they felt family presence benefits the family (72%), patients (59%) and the code team (41%). Perceived barriers were lack of space, increased staff stress, staff objections, interruptions of care, and lack of identified support person (72, 68, 56, 48, 44% respectively).

CONCLUSION:
Code team members have varied perceptions about family presence during CPR depending upon their role. This suggests that specific education strategies for the entire code team may be necessary to improve the family presence experience.
Abstract 18707: The Baseline Image Intensity Ratio, a Surrogate for Pre-existing Left Atrial Fibrosis, is Associated With Recurrence of Atrial Fibrillation Following Pulmonary Vein Isolation
Authors: Dewire Jane , Khurram Irfan , Zipunnikov Vadim , Beinart Roy , Spragg David , Marine Joseph , Berger Ronald , Halperin Henry , Zimmerman Stefan , Calkins Hugh , Nazarian Saman
Published: April 2024

Introduction:
Catheter ablation of AF is beneficial for many patients, but it is associated with a high AF recurrence rate that previously has been correlated with left atrial (LA) fibrosis on late gadolinium enhanced (LGE) MRI. We sought to test the association of LA fibrosis with recurrent post-ablation AF, using the image intensity ratio (IIR), a novel and standardized measure for quantification and inter-patient comparisons of LA fibrosis.

Methods:
Fifty consecutive AF patients (59.2±9.0 years, 74% men, 44% persistent AF) were enrolled and underwent LGE-MRI prior to initial AF ablation procedure. The local IIR was defined as the LA myocardial signal intensity of each sector in axial plane divided by the mean LA blood pool image intensity. The cohort was divided into four groups using mean IIR thresholds of 0.95. The mean follow-up was 9.0±4.6 months, and recurrences were documented with routine follow-up and symptom-prompted electrocardiography as well as phone calls.

Results:
Of 50 total patients, 11 (22%) experienced AF recurrence (4/28 paroxysmal AF (14.3%), and 7/ 22 persistent AF (31.8%)). The baseline IIR was higher in paroxysmal AF patients that experienced recurrence (1.0±0.18 vs. 0.81±0.08, p=0.001), but was similar in persistent AF patients with or without recurrence (0.84±0.12 vs. 0.88±0.14, p=NS). The Figure illustrates Kaplan-Meier survival analyses based upon baseline IIR derived patient groups.

Conclusions:
Baseline left atrial fibrosis is strongly associated with AF recurrence in patients with paroxysmal AF, but is unassociated with outcomes in patients with persistent AF.
Abstract 18744: Time Trends in the Population Attributable Risk for Cardiovascular Disease: Atherosclerosis Risk in Communities Study
Authors: Cheng Susan , Claggett Brian , Correia Andrew , Shah Amil , Gupta Deepak , Skali Hicham , Ni Hanyu , Coresh Josef , Solomon Scott
Published: April 2024

BACKGROUND:
Traditional cardiovascular disease (CVD) risk factors remain widely prevalent in the community. Whether relative contributions of risk factors to incident CVD may have changed over time, in the population at large or in important subgroups, is unclear.

METHODS:
We studied 13,541 participants (56% women, 26% black) in the Atherosclerosis Risk in Communities Study who were aged 52-66 years and free of CVD at visits 1 (1987-1989), 2 (1990-1992), 3 (1993-1995), or 4 (1996-1998). In this middle-aged sample at each visit, and in sex- and race-stratified analyses, we estimated multivariable-adjusted population attributable risks (PAR) for the 10-year incidence of new-onset CVD.

RESULTS:
Overall, the contributions of smoking (PAR 0.15 [95% CI 0.12-0.17] to 0.12 [0.10-0.14], P=0.05) and dyslipidemia (0.18 [0.10-0.24] to 0.09 [0.03-0.16], P=0.085) to CVD risk appeared to decrease from visit 1 to visit 4; the contributions of obesity (P=0.79), hypertension (P=0.70), and diabetes (P=0.28) were unchanged. The contribution of all risk factors combined was higher in women than men at visit 1 (P<0.001) but not by visit 4 (P=0.11) (Figure). The contribution of all risk factors combined appeared higher in blacks than whites at visit 1 (P=0.06) and this difference was more pronounced by visit 4 (P=0.02). Differences by sex (P=0.051) and race (P=0.089) in the contribution of hypertension to CVD risk had decreased and were borderline significant by visit 4. However, the contribution of diabetes remained substantially higher in women than men (P<0.001) and in blacks than whites (P<0.001) by visit 4.

CONCLUSION:
The contribution to incident CVD of all traditional risk factors combined is greater in blacks than whites, and this difference may be increasing. The CVD risks attributable to hypertension and diabetes have remained especially high, in women as well as blacks, highlighting the need for continued targeted risk factor modification particularly in these subgroups.
Abstract 18761: Non-Muscle Myosin Light Chain Kinase Mediates Vascular Endothelial Growth Factor Induced Vascular Hyperpermeability via Specificity Protein 1 During Asthmatic Inflammation
Authors: Shimizu Yuka , Sun Xiaoguang , Zhou Tong , Wang Ting , Garcia Joe G
Published: April 2024

INTRODUCTION:
Increased vascular permeability and accumulation of alveolar fluid are cardinal features of lung inflammation and asthma. Two targets for these responses are vascular endothelial growth factor (VEGF) and the non-muscle isoform of myosin light chain kinase (nmMLCK), a key regulator of vascular barrier function via actin-myosin mediated cell contraction. Both VEGF and nmMLCK mRNA and protein expression are upregulated in asthmatic patients. Supported by preliminary in vitro studies that demonstrate increased VEGF-induced nmMLCK expression, we propose a linkage between these two asthma targets and hypothesize that nmMLCK mediates VEGF induced vascular hyperpermeability in asthmatic inflammation.

Methods & Results:
mRNA quantified by qPCR showed increases in nmMLCK mRNA in lung biopsies from human asthmatic patients and ovalbumin (OVA, 0.4 mg/kg) challenged murine asthma model. OVA-challenged mice overexpressing nmMLCK in the endothelium (nmMLCKec/ec) exhibit increased airway pressure time index (APTI) and BAL protein levels compared to WT, whereas OVA-challenged nmMLCK-/- mice demonstrated significant attenuation of increases in APTI and BAL protein levels. Human pulmonary artery endothelial cells (HPAEC) treated with recombinant hVEGF (100ng/ml) increased nmMLCK mRNA and protein expression. In silico analysis of nmMYLK 5’ UTR 2.4 kb region and in vitro luciferase promoter assay in HPAEC revealed transcription factor binding sites of downstream effectors of VEGF signaling, with -400bp upstream of TSS being the critical region, which included the binding sites for the transcription factor, Sp1. Consistent with this, reduced Sp1 expression by siRNA attenuated VEGF-induced decrease in transendothelial electrical resistance (TER) as measured by electrical cell-substrate impedance sensing system.

CONCLUSIONS:
Our data demonstrate that nmMLCK induced by VEGF is mediated through Sp1 in lung EC. nmMLCK is a novel asthmatic target and represents a potential candidate for therapeutic modulation of asthmatic inflammation.
Abstract 18862: Wall Shear Stress in Pulmonary Hypertension
Authors: Smith Triston B , Kheyfets Vitaly O , Schroeder Theodore , Mueller Jeffrey , Lasorda David , Spotti Jennifer , Finol Ender A , Murali Srinivas
Published: April 2024

Pulmonary arterial hypertension (PAH) leads to morphometric remodeling of the pulmonary arteries. Computational fluid dynamics (CFD) modeling has the potential to reveal continuum metrics associated with the stress acting on the vascular endothelium in a non- invasive manner. We hypothesized that the PA endothelium of PAH patients will be subject to abnormal wall shear stress (WSS), and thus investigated the relationship of spatially averaged WSS (SAWSS) with invasive measurements of pulmonary vascular resistance (PVR) and compliance (C).

Methods:
Computed tomography angiography (CTA) and RHC were used to acquire images and hemodynamic data in 19 PH patients. Each patient’s pulmonary vascular tree was reconstructed from CT images up to 6 generations. The inlets and outlets were extended to 10 times their hydraulic diameters and a volumetric mesh created within element dimensions determined by a systematic mesh convergence study. Each CFD model was simulated using a structured tree outflow boundary condition. Constant flow rate simulations were performed using the numerical solver Fluent (ANSYS Inc., Lebanon, NH) after adjusting for patient-specific scaling parameters. Finally, SAWSS on the surface of the pulmonary arterial endothelium was obtained during post-processing. Correlations between SAWSS and hemodynamics were made.

Results:
Figure 1 shows a power-regression correlation between SAWSS and PVR, and linear-regression correlation between SAWSS and C. SAWSS decreases for increasing PVR and decreasing C.

Conclusions:
Pulmonary arterial WSS obtained by our CFD model can be used as a physiologically relevant quantitative metric of PAH severity, which likely precedes vascular and ventricular remodeling. Its application as a non-invasive surrogate for disease progression and evaluation of response to PH specific therapies needs further investigation.
Abstract 18926: Pre-Implant Surface EKG Screening Predicts the Arrhythmia Detection Vector Utilized by an Entirely Subcutaneous Implantable Defibrillator System
Authors: Moss Joshua D , Mino Lizbeth , Knight Bradley , Beshai John F , Nayak Hemal M , Burke Martin C
Published: April 2024

Objectives:
The subcutaneous ICD system (S-ICD) uses 3 electrodes under the skin to detect ventricular arrhythmias. Pre-implant surface EKG is performed to screen for sensing suitability prior to implant. We studied whether screening vectors pre-implant predict the final S-ICD detection vector selected post-implant.

Methods:
Pre- and post-implant sensing data from 51 patients who received the S-ICD at 2 centers were analyzed. The surface EKG data was collected using a Zoom™ programmer (Boston Scientific) in a configuration simulating the S-ICD sensing vectors (Figure). Surface EKG vectors deemed acceptable at screening were compared to the device-selected arrhythmia detection vector both at implant and during postural testing at hospital discharge.

Results:
On average, 1.8 +/- 0.6 pre-implant surface screening vectors were deemed acceptable. The detection vector selected 1) at implant and 2) at discharge matched an acceptable pre-implant vector in 80% and 78% of patients, respectively. The vector selected at discharge matched the implant vector in 56% of patients with 1 acceptable screening vector, versus 86% of patients with >1 acceptable screening vector (P=0.03). Vector at discharge was more likely to match a screening vector when the surface proxy for the “primary” sensing vector was deemed acceptable, as compared with the “alternate” sensing vector (P=0.01).

Conclusions:
The majority of patients had more than one acceptable sensing vector via pre-implant screening EKG. Acceptable sensing vectors determined pre-implant predict the detection vector ultimately selected after implant. In the majority of patients, postural changes at pre-discharge testing do not alter the optimal detection vector.
Abstract 18949: The Relationship of Central Obesity to Clinical Outcome After Percutaneous Coronary Intervention With Drug-Eluting Stent
Authors: Park Se Jun , Lim Hong Seok , Yang Hyoung Mo , Choi Byoung Joo , Choi So Yeon , Hwang Gyo Seung , Shin Joon Han , Tahk Seung Jea
Published: April 2024

Objectives:
Central obesity in patients with coronary artery disease is directly related with adverse cardiovascular events. The aims of this study were to examine the association of truncal fat accumulation with outcomes after percutaneous coronary intervention (PCI).

Methods:
In 782 patients (mean age: 60 ± 11 years, 494 male, 63.2%) who underwent PCI for 840 coronary lesions with DES between January 2005 and June 2008, dual-energy X-ray absorptiometry (DXA) was performed to assess total body fat and regional body fat distribution. The primary outcome was defined as a composite of major adverse cardiac events (MACE) including cardiac death, myocardial infarction, and ischemia-driven target vessel revascularization (TVR).

Results:
During a median follow-up of 54 months, 82 cases of MACE (12 cardiac death, 2 myocardial infarction and 72 TVR) occurred. Percentage truncal fat mass to both legs fat mass ratio (%FMtrunk/FMleg) (2.5 vs 2.2, p=0.001) were higher in MACE group than no MACE group. To determine independent risk factors for MACE, we performed multiple logistic regression analysis and revealed that %FMtrunk/FMleg was an adjusted risk factor for adverse cardiac events after PCI (p=0.011), but not BMI, total fat mass.

Conclusion:
Poor outcome after PCI with DES is more associated with %FMtrunk/FMleg representing central body fat distribution than other obesity parameters, such as BMI. Therefore patients who had coronary angioplasty with DES might need to have therapeutic intervention for secondary prevention.
Abstract 18995: Radiation-Induced Constrictive Pericarditis(r-cp) With Normal Left Ventricular Ejection Fraction is Associated With Lower Global and Regional Myocardial Mechanics Compared to Non-Radiation-Induced Constrictive-Pericarditis(cp)
Authors: Matshela Mamotabo R , Blauwet Lori A , Pellikka Patricia A , Oh Jae K , Villarraga Hector R
Published: April 2024

Background:
CP/R-CP may be associated with subtle features of ventricular dysfunction which are not easily detectable with the use of conventional echocardiographic modalities. The aim of this study was to evaluate myocardial mechanics by 2D-STE (2 Dimensional speckle-tracking echocardiography) between CP and R-CP. We hypothesized that strain/ strain rate (S/SR) would be worse in the R-CP patients due to radiation-induced myocardial injury.

Methods:
We analyzed 180 patients (62% male, age 62±13 years, 127 CP and 53 R-CP) with suitable echocardiographic images and normal left ventricular ejection fraction (LVEF>55%). The two groups were similar in terms of age, cardiovascular symptoms, risk factor profile and LVEF (Table). Selected images were analyzed off-line using Velocity Vector Imaging technology. The diagnosis of CP was based on clinical parameters as well as echocardiography and/or hemodynamic cardiac catheterization. Patients in whom radiation therapy was the primary etiology of CP were classified as R-CP. Global and segmental circumferential, radial, longitudinal, systolic and early diastolic strain and strain rate were analyzed in all patients.

Results:
Global and segmental radial (GRadS), global longitudinal (GLS), global basal (GBS), global mid-segment (GMS), septal wall (SWS), and anterior wall (AWS) strain was significantly reduced in the R-CP patients compared with the CP patients (Table). Antero-septal and anterior wall diastolic strain and strain rates (AS + AW Sre, SR) were reduced in the R-CP group. The best differentiators between the two groups were antero-septal (SAS), basal anterior (BAS) and mid anterior (MAS) segmental strain, based on receiver operating characteristic (ROC) and area under the curve (AUC) analysis. ROC calculations were AUC: SAS 0.67, SBA 0.69, and SMA 0.71.

Conclusion:
The study showed that compared with CP, R-CP is associated more with myocardial dysfunction, likely due to radiation-induced myocardial injury.
Abstract 19023: Left Ventricle Diastolic Dysfunction With Preserved Ejection Fraction, Who is at Higher Risk?
Authors: Kumar Arnav , Sharif Roozbeh , Khan Adnan , Morsy Mohammad , Khalife Wissam
Published: April 2024

Background:
Prevalence of left ventricular diastolic dysfunction (LVDD) in a multi ethnic population and the associated risk factors have not been well studied. To risk stratify patients with LVDD, demographics should be further analyzed in a population representative of the nation’s diversity. We aimed to investigate how race and age correlate with the presence and severity of LVDD in a multi-ethnic population.

Methods:
In a cross-sectional study, we reviewed the medical records of 2702 randomly selected patients who presented to the echocardiographic lab in a tertiary care academic center between 2008 and 2011. Diastolic function was evaluated based on echocardiographic characteristics. Demographic information (including self-reported race) and co-morbid clinical conditions were compared between patients with normal diastolic function and those with LVDD. Mixed races were excluded from the analysis. Using logistic regression, we conducted a multivariate analysis to examine the association of demographic variables with presence and severity of LVDD, after adjusting for co-morbid clinical conditions.

Results:
The study population included 2702 patients: average (SD) age of 60.3 (16.2), 1853 (68.6%) with LVDD, 1301 (48.4%) females and 848 (31.4%) African-Americans (AA). AAs constituted 213 (25.1%) of patients with normal diastolic function, compared to 660 (35.6%) patients with LVDD (OR: 1.6, 95%CI: 1.2, 2.1, p<0.0001). Multivariable analysis indicated that older age (p<0.0001) and AA race (p=0.0031) are independent correlates of LVDD, after adjusting for potential clinical confounders such as body mass index, high blood pressure, chronic kidney disease, coronary artery disease, diabetes mellitus, right ventricular systolic pressure and other co morbid conditions. AA patients were also found to have a higher likelihood of more severe stages of diastolic dysfunction when compared to other ethnic groups, after adjusting for age and co-morbid conditions. However, patient gender was not associated with presence or severity of LVDD.

Conclusion:
Older age and African-American ethnicity increases the risk and severity of LVDD, regardless of clinical co-morbid conditions.
Abstract 19071: A Novel Role of E2f1 in the Regulation of Bone Marrow Progenitor Cell Oxidative Metabolism and Ischemic Cardiac Repair
Authors: Xu Shiyue , Tao Jun , Qin Gangjian
Published: April 2024

Background:
We have previously shown that knockout of E2F1 in mice enhances angiogenesis following induction of hind limb ischemia. Recent studies suggest that E2F1 can act as a switch between glycolysis and oxidative phosphorylation, and suppression of E2F1 enhances oxidative phosphorylation in a variety of cell types. Since an increase in oxidative phosphorylation in stem/progenitor cells is often associated with cell differentiation, we

hypothesize

that E2F1 regulates bone marrow (BM) progenitor cell differentiation thereby impacts on ischemic cardiac repair by switching metabolism status of the cells from glycolysis to oxidative phosphorylation.

Methods and Results:
We cultured bone marrow (BM) Lin
-
progenitor cells under hypoxic and normxic conditions for 24 h, then measured the expression of metabolism related genesand evaluated cell proliferation and differentiation. We also performed adoptive BM transplantation to reconstitute BM of WT mice with E2F1
-/-
or WT BM, followed by surgical induction of myocardial infarction (MI), to compare the role of BM E2F1 in the cardiac repair
in vivo
. We found that the expression level of genes in the mitochondria respiration chain in the E2F1
-/-
BM Lin
-
progenitor cells is in average about 2 holds higher than those in WT cells (
P
<0.05, n=3). After culture in the EPC differentiation medium for 7 days, the expression levels of EPC markers, CD31 and KDR , were significantly higher in E2F1
-/-
cells than in WT control cells (
P
<0.05, n=3). Although there was no significant difference in the proliferating rate between WT and E2F1
-/-
BM Lin
-
progenitor cells cultured in normoxia, when cultured under hypoxic condition the proliferating rate of E2F1
-/-
cells were markedly greater than that of WT cells (
P
<0.05, n=3). Consistently, the infarcted size in mice transplanted with E2F1
-/-
eGFP
Tg
BM was significantly smaller than in mice transplanted with WTeGFP
Tg
BM (
P
<0.01, n=5).

Conclusions:
Genetic deletion of E2F1 in the BM progenitor cells enhances oxidative metabolism that may result in enhanced differentiation towards endothelial lineage and increased proliferation in the ischemic/hypoxic tissue environment. Therefore, inhibition of E2F1 in BM progenitor cells may improve the recovery from cardiac ischemic injury.
Abstract 19088: Synstatin: A Peptide-Based Switch to Alter the Phenotype of Vascular Smooth Muscle Cells
Authors: Chaterji Somali , Pham Kimberly , Choe Seung , Lam Christoffer , Baker Aaron
Published: April 2024

Introduction:
Vascular proliferative diseases such as primary atherosclerosis, postangioplasty restenosis, and transplant vasculopathy reduce the likelihood of success in vascular interventions. The ability of activated vascular smooth muscle cells (vSMCs) to contribute to the vascular lesion mass and to the inflammatory state of the vessel wall after injury is well known. An understanding of the mechanistic basis of vSMC activation can result in more effective therapies for improving vascular outcomes.

Hypothesis:
Prior work has suggested that loss of the transmembrane receptor, syndecan-1, can de-differentiate vSMCs. Given the extended reach of the glycosaminoglycan chains of syndecan-1, we hypothesized that the interaction of syndecan-1 with other receptors and matrix molecules can affect vSMC phenotype. It has been identified that the ectodomain of syndecan-1 can regulate the activation of α
v
β
3
and α
v
β
5
integrins on mammary carcinoma cells, fibroblasts, and endothelial cells. Further, the peptide synstatin (SSTN) has been found to inhibit this interaction of syndecan-1 with the α
v
β
3
and α
v
β
5
integrins. Thus, we further hypothesized that SSTN could modulate vSMC phenotype, affording mechanistic insights into syndecan-1’s role in vSMC differentiation.

Findings:
We performed gene expression studies for studying the effect of SSTN addition on the differentiation of primary human aortic SMCs. Real time PCR (n=4) indicated lower levels of smooth muscle-specific differentiation markers [[Unable to Display Character: –]] smooth muscle α-actin, calponin, and smoothelin in SSTN-treated vSMCs. Further, higher levels of the inflammatory markers [[Unable to Display Character: –]] IL-6, ICAM-1, and VCAM-1, and of heparanase, an endoglycosidase which cleaves heparan sulfate (GAG) chains, were observed. This indicates that an SSTN-based tumor stopper, as proposed in literature, could potentially result in vSMC activation and increase the inflammatory state of the blood vessel wall.

Conclusion:
Taken together, our results support a positive role for syndecan-1 in promoting vSMC differentiation, reducing the chances of intimal hyperplasia after vascular injury. It also indicates that the interaction of syndecan-1 with the integrins α
v
β
3
and α
v
β
5
may be a necessary condition for the differentiation of vSMCs.