bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 360: Evaluating the Challenges of Functional Outcomes in Traumatic Brain Injury Research: Timing of Follow-Up, Prognostic Models, and Missing Data
Authors: Zelnick Leila R , Morrison Laurie J , Devlin Sean M , Bulger Eileen M , Brasel Karen J , Sheehan Kellie , Minei Joseph P , Kerby Jeffrey D , Tisherman Samuel A , Rizoli Sandro , Karmy-Jones Riyad , van Heest Rardi , Newgard Craig D ,   The Resuscitation Outcomes Consortium Investigators
Published: April 2024

Background:
Traumatic brain injury (TBI) is common and debilitating. Randomized trials of interventions for TBI usually assess effectiveness by using long-term functional neurological outcomes but this is costly and difficult. If patient characteristics available at hospital discharge are predictive of 6-month functional outcome, then shorter-term outcomes may be adequate for use in future clinical trials. We evaluated models to predict long-term outcomes after TBI from short-term functional measures and easily obtainable demographic and injury characteristics as covariates, using data from a previously published randomized clinical trial.

Methods:
The Hypertonic Saline TBI trial of the Resuscitation Outcomes Consortium (ROC) enrolled 1282 TBI patients but had 15% missing data for the primary outcome of 6-month Glasgow Outcome Score Extended (GOSE). We evaluated patterns of missing data, whether functional outcome obtained earlier than six months would adequately reflect 6-month GOSE, and three prognostic models that predict 6-month severe disability (GOSE ≤ 4) via logistic regression using covariates and outcomes at discharge.

Results:
Patients with missing 6-month GOSE had less severe injuries, higher neurological function at discharge (GOSE), and shorter hospital stays than patients whose GOSE was obtained. Of 1066 (83%) patients with available discharge and 6-month outcomes, 71.2% of patients had the same functional status (severe disability/death vs. moderate /no disability) after 6 months as at discharge, 28% had an improved functional status, and 1% had worsened. Performance was excellent (AUC between 0.88 and 0.91) for all three prognostic models and calibration adequate for two models (p-values 0.22 and 0.85).

Conclusion:
Missing data was more common in healthier patients suggesting an ascertainment bias if the missing data were ignored during analysis. Shorter duration follow-up appears inadequate in representing long-term functional neurological outcome following TBI; however, all three prognostic models were highly predictive of long-term outcome. Our results support the more widespread use of multiple imputation of the standard 6-month GOSE when the primary outcome cannot be obtained through other means.
Abstract 15846: Disturbed flow-induced p90RSK activation elicits EC dysfunction and atherosclerosis formation via inhibiting de-SUMOylation
Authors: Heo Kyung-Sun , Le Nhat-Tu , Cushman Hannah J. , Giancursio Carolyn J. , Chang Eugene , Woo Chang-Hoon , Taunton Jack , Yeh Edward T.H. , Fujiwara Keigi , Abe Jun-ichi
Published: April 2024

Kyung-Sun Heo, 2013 Finalist and Presenting Author
Abstract 11082: Exome Sequencing Implicates the Burden of Rare Potassium Channel Variants in the Risk of Drug Induced Long QT Syndrome
Authors: Weeke Peter , Mosley Jonathan D. , Hanna David , Shaffer Christian , Delaney Jessica T. , Wells Quinn S. , Van Driest Sara , Karnes Jason H. , Ingram Christie , Guo Yan , Shyr Yu , Norris Kris , Kannankeril Prince J. , Ramirez Andrea H. , Smith Joshua D. , Mardis Elaine R. , Nickerson Deborah , George Alfred L. , Roden Dan M.
Published: April 2024

Peter Weeke, 2013 Finalist and Presenting Author
Abstract 13011: A Swimmer with Ventricular Tachycardia: Multiple Wavelets or a Pebble in a Pond?
Authors: Pelchovitz Daniel J. , Shen Sharon , Knight Bradley P. , Chicos Alexadru B.
Published: April 2024

Daniel J. Pelchovitz, 2013 Finalist and Presenting Author
Abstract 14227: A Pitx2-microRNA pathway that delimits sinoatrial node development and inhibits predisposition to atrial fibrillation
Authors: Wang Jun , Bai Yan , Li Na , Greene Stephanie B. , Zhang Min , Tao Ye , Wehrens Xander H. T. , Martin James F.
Published: April 2024

Jun Wang, 2013 Finalist and Presenting Author
Abstract 15313: The association between diet quality and mortality in incident type 2 diabetic women
Authors: Shin Hyun Joon , Kim Ja Young , Cho Eunyoung , Jung Seungyoun , Rimm Eric , Rosner Bernard , Manson JoAnn E. , Hu Frank B.
Published: April 2024

Hyun Joon Shin, 2013 Finalist and Presenting Author
Abstract 10093: Obesity paradox is not recognized in chronic heart failure patients with metabolic syndrome
Authors: Narumi Taro , Watanabe Tetsu , Kadowaki Shinpei , Otaki Yoichiro , Nishiyama Satoshi , Takahashi Hiroki , Arimoto Takanori , Shishido Tetsuro , Miyashita Takehiko , Miyamoto Takuya , Kubota Isao
Published: April 2024

Taro Narumi, 2013 Finalist and Presenting Author
Cellular and Molecular Mechanisms of Diabetes-Accelerated Atherosclerosis
Authors: Bornfeldt Karin
Published: April 2024

I will be very honored to present the 2013 Russell Ross Memorial Lecture in Vascular Biology. I will discuss our current understanding of the cellular and molecular mechanisms whereby diabetes accelerates atherosclerosis, based on data primarily from mouse models. Diabetes accelerates the formation of atherosclerotic lesions in hyperglycemic mouse models in which plasma lipid levels are unaltered by diabetes. Diabetes-accelerated lesion formation is driven, at least in part, by the altered function and properties of myeloid cells; cells that contribute to an increased inflammatory vascular state. Based on our recent studies, the enzyme acyl-CoA synthetase 1 (ACSL1), which converts long-chain fatty acids into their acyl-CoA derivatives, has emerged as causal to the enhanced lesion initiation associated with diabetes. ACSL1 is expressed at higher levels in monocytes/macrophages from diabetic mice and humans, as compared to controls, and is induced by inflammatory mediators in these cells. Interestingly, the protective effect of myeloid ACSL1-deficiency is obvious in diabetic mice, but not in non-diabetic mice, indicating that ACSL1-deficiency targets a pathway that is selectively activated by diabetes. Diabetes also accelerates progression of atherosclerotic lesions to advanced plaques characterized by hemorrhage. This effect is dependent on diabetes-induced dyslipidemia. Important questions for future research are whether ACSL1 and other factors identified in mouse models play equally important roles in diabetes-accelerated atherosclerosis and cardiovascular disease in humans.
Abstract 83: Barriers to Implementation of the PulsePoint Smartphone Application
Authors: Brooks Steven C , Worthington Heather C , Gonedalles Toula E , Bobrow Bentley , Morrison Laurie J
Published: April 2024

Background:
PulsePoint is a smartphone application that alerts users in the vicinity of a cardiac arrest to the location of the emergency to facilitate bystander resuscitation. Identifying barriers to implementation provides an opportunity to increase the efficacy of the application.

Objective:
To identify potential barriers to bystander resuscitation facilitated by the PulsePoint application.

Methods:
A request for survey participation was sent to all alerted smartphones between June 28, 2012 and May 1, 2013. Only one request for participation was sent to potential respondents. The survey was structured with multiple choice and free text responses administered via Survey Monkey. PulsePoint was active in 10 US EMS agencies over the course of the survey (population served ~ 1.7 million).

Results:
Of 2790 PulsePoint users sent a CPR notification and request for survey completion, 23.8 % completed our survey (663/2790). Figure 1 details the responses to key questions in the survey and identifies potential barriers. Approximately 37% of survey respondents did not receive an alert, despite the system sending one. Seventy-eight percent of users who received an alert did not respond (328/419). Most cited being busy with a task they could not abandon or felt the location of the emergency was too far away. Approximately 78% of those who arrived on scene (54/69) did not find a victim in cardiac arrest. Of those users who arrived before EMS and found an unconscious victim who was not breathing normally, 6/7 (86%) performed CPR.

Conclusion:
Several potential barriers to implementation have been identified including specificity of the alerts for actual cardiac arrest and the radius of alert around a cardiac arrest episode. The very high proportion of respondents performing bystander CPR when arriving on scene prior to EMS (86%) suggests that optimized PulsePoint implementation, with identified barriers addressed, may improve community-level bystander CPR rates.
Abstract 84: Effects of Edaravone on Brain Apoptotic Gene in CA/CPR Rats
Authors: Chen Meng H , Xie Lu
Published: April 2024

Edaravone(3-methyl-1-phenyl-2-pyrazolin-5-one), a strong novel free radical scavenger, is used in clinically as a novel neuroprotective agent for the treatment of patients with acute ischemic stroke. We assessed the hypothesis that the neuroprotective effect of edaravone corresponding with brain apoptosis could improvethe survival outcomes in a rat model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR).

Adult male Sprague-Dawley rats were divided into saline, edaravone groupssubjected to sham group (sham surgery, n=10), saline group (CA for 5 min following CPR and intravenous ejection of saline 1.5 ml/kg, n=20), edaravone (CA for 5 min following CPR and intravenous ejection of edaravone 3 mg/kg, n=20)groups. The resuscitated animals were observed for 72 h after the restoration of spontaneous circulation. The rat survival time, survival rate was assessed and the expression of caspase-3, caspase-8, Bax and Bcl-2mRNA at 12, 24, 48 and 72 hours in hippocampus was measured by real time-PCR.

Edaravone markedly enhanced the survival time and rate of rats (Kaplan-Meier analysis) after CA/CPR compared to saline group [(70.00±26.69) h, 95% CI (17.67-122.33)] vs[(23.00±3.91) h, 95% CI (15.33-30.67)] and (45% vs. 25%, χ2=4.900, P=0.027). The expression of apoptotic gene mRNA was significant upregulation (except caspase-8 and Bax in edaravone group at 72 h) in both the saline and edaravone groups (P<0.05) compared to sham group. Edaravone significantly decreased the expression of caspase-3, caspase-8 and Bax mRNA (P<0.05) and facilitate Bcl-2 expression (P<0.05) compared to saline group (Tab1-4). This study suggests that (i)CA/CPR results in upregulation of pro-and anti-apoptosis; (ii)edaravone suppresses the up-regulation of the pro-apoptotic gene expression and facilitates the expression of anti-apoptotic gene in the hippocampus, involved in the improvement of the survival outcomes after CPR.
Abstract 9249: Percutaneous Closure versus Medical Therapy for Cryptogenic Stroke in Patients With a Patent Foramen Ovale: A Meta-Analysis of Randomized Controlled Trials
Authors: Pickett Christopher , Villines Todd , Ferguson Michael , Hulten Edward
Published: April 2024

Objectives:
To systematically review and perform a meta-analysis of randomized controlled trials(RCT) comparing percutaneous closure of patent foramen ovale(PFO) to medical therapy in patients with cryptogenic stroke or transient ischemic attack(TIA).

Background:
Up to 61% of patients with cryptogenic stroke under the age of 55 years have been found to have a PFO. Observational studies have demonstrated reductions in recurrent, neurologic events with PFO closure compared to medical therapy. Recent RCT have shown non-significant trends toward benefit.

Methods:
We systematically searched for RCT of percutaneous PFO closure versus antiplatelet or anticoagulation medical therapy in patients with cryptogenic stroke or TIA and performed a meta-analysis of treatment outcomes. The primary end point was combined death, stroke, or TIA as defined by each study.

Results:
Three RCT of 2303 patients were included. In all, 1150 patients underwent PFO closure and 1153 received medical therapy and were followed over a median of 2.6(2.0-4.1) years. The pooled incidence of the primary end point was 1.2(95% confidence interval:0.2-2.3) events/100 patient-years in the PFO closure group and 1.8(0.7-2.9) in the medical therapy group(p=0.32), with a number needed to treat(NNT) of 167(100-500). The corresponding pooled hazard ratio(HR) was 0.67(0.44-1.01,p=0.054) in favor of PFO closure. PFO closure was associated with an increased incidence of atrial fibrillation, relative risk =3.51(1.44-8.55,p=0.006). When stratified by device, the Amplatzer™ showed a significant stroke prevention benefit, HR=0.44(0.21-0.95,p=0.037).

Conclusions:
In comparison to medical therapy alone, PFO closure trends toward decreased hazard of combined events, although the absolute event reduction is small with a high NNT in the population studied.
Abstract 9364: Drug Eluting Stents Appear Superior to Bare Metal Stents for Vein Graft Pci in a Propensity Matched Cohort
Authors: Safwan Kassem , Jones Dan , Rathod Krishna , Gallagher Shaun , Guttmann Oliver , Weerackody Roshan , Jain Ajay , Knight Charles , Mathur Anthony , Wragg Andrew
Published: April 2024

Background:
Research trials have shown improved short-term outcome with drug-eluting stents (DES) over bare metal stent (BMS) in Saphenous vein graft (SVG) PCI, primarily by reducing target vessel revascularization (TVR) for In-Stent Restenosis (ISR).

Because of the high event rates in these patients it is not clear if these benefits are maintained long term. We compared the outcomes in patients undergoing SVG stent implantation treated with DES or BMS, over a prolonged follow-up period using a propensity matched analysis.

Methods:
Clinical information was analysed from a prospective database on 512 patients who underwent PCI for SVG lesions between 2003 and 2010. 293 patients had PCI with BMS and 219 with DES. Propensity scores representing the estimated probabilities of patients receiving either DES or BMS were developed based on 15 observed baseline covariates in a logistic regression model with stent type as the dependent variable. The nearest-neighbour-matching algorithm with Greedy 5-1 Digit Matching was used to produce two patient cohorts of 219 patients each balanced for baseline factors.

We assessed major adverse cardiac events (MACE) ) out to a median of 3.3 years (IQR: 2.1-4.1)

MACE defined as •All Cause mortality •Myocardial infarction (MI)

•Target vessel revascularisation (TVR)

•Stroke Results There was a significant difference in MACE between the two groups in favour of DES (17.9% DES v 31.2% BMS group [P=0.04] over the 5-year follow-up.

MACE was driven by ISR in both groups and the difference between groups was due to increased TVR in the BMS group. There was no difference in death, MI or stroke.(Figure 1)

Adjusted Cox analysis confirmed a decreased risk of MACE for DES compared with BMS 0.75 (95% confidence intervals 0.52-0.94) with no difference in the hazard of all cause mortality (HR: 1.08 95% CI: 0.77-1.68).

Conclusion:
In our cohort of patients who had PCI for treatment of SVG disease the use of DES resulted in lower MACE rate compared to BMS over a 5-year follow-up.
Abstract 9391: Cyclic Variation of Heart Rate Score by Holter ECG for screening Sleep Disordered Breathing in Heart Failure Patients
Authors: Shimizu Takeshi , Yoshihsa Akiomi , Iwaya Shoji , Miyata Makiko , Abe Satoshi , Sato Takamasa , Suzuki Satoshi , Sugimoto Koichi , Yamaki Takayoshi , Kunii Hiroyuki , Nakazato Kazuhiko , Suzuki Hitoshi , Saitoh Shu-ichi , Takeishi Yasuchika
Published: April 2024

Background:
Sleep disordered breathing (SDB) has a critical association with cardiovascular mortality and morbidity, especially in patients with heart failure (HF). However, because of the complexity to refer the polysomnography, the majority of SDB patients remain undiagnosed. On the other hand, the abnormality of heart rate variability has been reported in patients with SDB. To explore an efficient ECG-based screening tool for SDB, we examined the usefulness of cyclic variation of heart rate score (CVHRS) by Holter ECG in HF patients.

Methods and Results:
In this study, 110 patients with HF (mean age 58.6 years, body mass index 23.6, left ventricular ejection fraction 45.5%) were enrolled. The exclusion criteria were the presence of atrial fibrillation and receiving implantable pacemaker device therapy. We simultaneously performed Holter ECG and polysomnography in night time, and measured apnea-hypopnea index (AHI) and CVHRS. We determined the temporal position of the individual dips comprising the CVHRS, using time-domain methods. CVHRS was measured as cyclic and auto correlated dips in smoothed interbeat interval time series. There were 77 patients with mild to moderate SDB (5≤AHI<30/h) and 26 patients with severe SDB (AHI ≥30/h). There was a significant positive correlation between CVHRS and AHI (R=0.60, P<0.001). From the ROC analysis, CVHRS (a cut off value of 30) identified severe SDB with sensitivity 82%, specificity 77%, positive predictive value (PPV) 78%, negative predictive value (NPV) 81% and area under the curve (AUC) 0.83.

Conclusions:
CVHRS determined by Holter ECG is a useful screening index for severe SDB in HF patients.
Abstract 94: Performance of High-Sensitivity Cardiac Troponin T in Etiologic Diagnosis After Out-of-Hospital Cardiac Arrest
Authors: Geri Guillaume , Mongardon Nicolas , Dumas Florence , Chenevier-Gobeaux Camille , Varenne Olivier , Jouven Xavier , Vivien Benoit , Mira Jean-Paul , Empana Jean-Philippe , Spaulding Christian , Cariou Alain
Published: April 2024

Purpose:
Early identification of the cause of out-of-hospital cardiac arrest (OHCA) remains a challenge. Our aim was to determine whether high-sensitivity cardiac troponin T (HsTnT) was useful to diagnose a recent coronary artery occlusion as the cause of OHCA.

Methods:
Retrospective study including OHCA patients evaluated by systematic coronary angiogram at hospital admission. HsTnT was assessed at ICU admission. Predictive factors of a recent coronary occlusion were identified by logistic regression. Net reclassification improvement (NRI) was calculated to estimate the potential enhancement of prediction with HsTnT.

Results:
During the 5 years study period, 272 patients (median age 60y, 76.5% men) were included, and a culprit coronary occlusion was found in 133 (48.9%). Median HsTnT at admission was 551 (IQR 203-2551) ng/l, up to three times higher in patients with compared to those without a recent coronary occlusion (1184 vs. 351 ng/l; p<0.0001). The optimum HsTnT cut-off to predict a recent coronary occlusion was 575 ng/l (sensitivity 65.4%, specificity 65.5%). In multivariate analysis, current smoking (OR 3.2 95%, 95%CI 1.62-6.33), time from collapse to BLS < 3 minutes (OR 2.11, 95%CI 1.10-4.05), initial shockable rhythm (OR 5.29, 95%CI 2.06-13.62), ST-segment elevation (OR 2.44, 95%CI 1.18-5.03), post-resuscitation shock onset (OR 2.03, 95%CI 1.01-4.07) and HsTnT ≥ 575ng/l (OR 2.22, 95% CI 1.16-4.27) were associated with the presence of a recent coronary occlusion. The AUROC curves of the multivariate model identified above were not statistically better than those of the same model with established risk factors but without HsTnT (AUROC curves= 0.78 vs. 0.79; p=0.23). Nevertheless, adding HsTnT to established risk factors of recent coronary occlusion identified above provided a non-significant NRI of -0.43%. Reclassification was not better in the subgroup of patients without ST-segment elevation (NRI= 0.105±0.078, p=0.18).

Conclusions:
Admission HsTnT is increased after OHCA and is an independent factor of a recent coronary occlusion. However, HsTnT does not seem to be a strong enough diagnostic tool to select candidates for emergent coronary angiogram in OHCA survivors.
Abstract 9432: Superior Long-term Prognostic Impact of Angiotensin Converting Enzyme Inhibitors to Angiotensin II Receptor Blockers After ST-Elevation Myocardial Infarction
Authors: Hara Masahiko , Sakata Yasuhiko , Nakatani Daisaku , Suna Shinichiro , Usami Masaya , Matsumoto Sen , Nishino Masami , Sato Hiroshi , Kitamura Tetsuhisa , Nanto Shinsuke , Hori Masatsugu , Komuro Issei ,   the OACIS Investigators
Published: April 2024

Background:
Although international guidelines recommend angiotensin-converting enzyme inhibitor (ACEI) as the first-line therapy after ST-elevation myocardial infarction (STEMI), the prescription of angiotensin II receptor blockers (ARB) is surpassing that of ACEI worldwide. Here, we examined whether the long-term benefits of ARB are comparable with those of ACEI in post-STEMI patients in the real-world setting.

Methods:
We compared 5-year survival benefits of ACEI and ARB in 7,547 consecutive STEMI patients registered with the Osaka Acute Coronary Insufficiency study between 1998 and 2010. Study subjects were divided into 3 groups: patients treated with ACEI (n=3,794), ARB (n=1,786), or without either drug (n=1,967) at survival discharge.

Results:
A total of 545 deaths were recorded during a median follow-up period of 3.9 years after survival discharge. The prescription rate of ARB at discharge increased from 1998 to 2010, whereas that of ACEI decreased (p<0.001). Cox regression analysis revealed that treatment with either ACEI or ARB at discharge was associated with reduced 5-year mortality (adjusted hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.56-0.81, p<0.001; and HR 0.76, 95% CI 0.60-0.96, p=0.021, respectively). However, Kaplan-Meier estimates and Cox regression analyses based on propensity score (PS) revealed that ACEI was associated with significantly better survival than ARB from 2 to 5 years after survival discharge (adjusted HR 0.57, 95% CI 0.40-0.81, p=0.002) despite comparable prognostic impacts for the first 2 years (adjusted HR 1.03, 95% CI 0.71-1.49, p=0.878). These findings were also confirmed in a PS-matched population.

Conclusions:
Although ACEI and ARB treatment showed comparable prognostic impacts in the first 2 years after STEMI onset, treatment with ACEI was associated with better survival from 2 to 5 years. Further investigations are warranted to confirm the results.
Abstract 9445: Increased Carotid Intima-Media Thickness Compared to Carotid Artery Plaque and Coronary Artery Calcium Presence for Predicting Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Gepner Adam D , Young Rebekah , Delaney Joseph C , Tattersall Mattew C , Blaha Michael C , Post Wendy S , Gottesman Rebecca F , Kronmal Richard , Budoff Matthew J , Burke Gregory L , Folsom Aaron R , Liu Kiang , Kaufman Joel , Stein James H
Published: April 2024

Background:
As a clinical tool, carotid ultrasound can re-classify patients to a higher cardiovascular disease (CVD) risk level when the intima-media thickness (CIMT) is high (≥75th percentile for age, sex, and race) or carotid plaque (CP) is present. No studies have directly compared the predictive utility of CP presence, high common carotid artery IMT, and coronary artery calcium (CAC) presence for incident CVD events in a large, multi-ethnic cohort with extended follow up.

Methods:
CVD events (CVD death, coronary heart disease [CHD] and stroke), and transient ischemic attack (TIA) were prospectively assessed in 6,779 MESA participants free of CVD at baseline. CP presence was evaluated and compared to common carotid artery IMT and CAC presence using Cox proportional hazards models, C-statistics and net reclassification indices. Multiple imputation was used to account for missing data.

Results:
At baseline, participants were mean (standard deviation) 60.3 (9.4) years old. CAC was present in 49.9% and CP was present in 46.7% subjects. Baseline mean left and right common carotid artery IMT were 0.754 (0.210) mm and 0.751 (0.187) mm. After a median of 8.5 years, 538 CVD events, 388 CHD events and 196 stroke/TIAs were observed. CAC presence was a stronger predictor of CVD, CHD and stroke/TIA than any carotid ultrasound measure (Table). Compared to traditional risk factors, c-statistics for CVD and CHD increased most by the addition of CAC presence (p<0.001) followed by CP presence (CVD, p=0.03; CHD p=0.04). Neither CAC presence nor any carotid measure improved the c-statistic for stroke/TIA (p>0.3). Common carotid artery IMT did not improve the predictive value of CP presence.

Conclusion:
CAC presence predicts incident CVD, CHD, and stroke/TIA events better than CP presence, high common carotid artery IMT, or their composite. CAC presence is a better CVD prediction tool than carotid ultrasound measures in healthy, middle-aged adults.
Abstract 9508: Neutrophil to Lymphocyte Ratio Predicts Short and Long Term Mortality After Revascularized ST Elevation Myocardial Infarction
Authors: Sawant Abhishek C , Adhikari Prabhat , Mills Paul K , Srivatsa Sanjay S
Published: April 2024

Introduction:
Several biomarkers of inflammation have been implicated in the pathogenesis of acute coronary syndromes. The role of inflammatory markers in predicting short and long term survival after revascularized STEMI remains poorly defined.

Patient and methods:
We retrospectively evaluated 250 consecutive STEMI patients admitted to a tertiary care center over one year. Exclusion criteria included:acute sepsis, trauma, recent surgery or underlying malignancy. Data analyzed included demographics, clinical presentation, leukocyte markers, electrocardiograms, therapy and major adverse cardiac events.

Results:
Mean age was 62±15 years, 70.4% subjects were males, almost equal number were Caucasians (49.4%) and non-Caucasians with mean follow up of 571±291 (Median=730) days. Considering available inflammatory markers, univariate predictors of mortality included only White Cell Count (14.52±8.09*10
3
/microliter;p<0.001) and neutrophil to lymphocyte ratio [NLR] (9.12±8.75;p=0.011). Multivariate regression analysis of all univariate predictors revealed NLR (OR=2.64;p=0.026), female gender (OR=5.35;p<0.001), cerebrovascular accident history (OR=3.36;p=0.023), low glomerular filtration rate (OR=0.98;p=0.012) and cardiac arrest on admission (OR=17.43;p<0.001) as independent predictors of 2-year mortality. NLR was subdivided based on an optimal cut off value (OCV) of 7.4, when combined with Thrombolysis in Myocardial Infarction (TIMI) Score provided the highest predictive power for mortality with Area Under the Curve (AUC) of 0.799 (95 CI:0.734,0.865;p<0.001). Short term (30 days) and long term (2-years) mortality stratified by NLR (Figure 1-A) and Kaplan Meier survival analysis (Figure 1-B) are illustrated.

Conclusion:
NLR based on OCV of 7.4 is an excellent predictor of short and long term survival with additive prognostic value to conventional clinical and angiographic scoring systems used for revascularized STEMI patients.
Abstract 9533: Retention of Endothelial Progenitor Cells in Bone Marrow in a Murine Model of Endogenous Tissue Plasminogen Activator (tPA) Deficiency in Response to Critical Limb Ischemia
Authors: Yip Hon-Kan , Chua Sarah , Tsai Tzu -Hsien , Sheu Jiunn-Jye
Published: April 2024

Background:
This study tested the hypothesis that tissue plasminogen activator (tPA) is crucial for regulating endothelial progenitor cell (EPC) mobilization from bone marrow to circulation in murine critical limb ischemia (CLI) by ligating left femoral artery.

Methods and Results:
Wild-type (C57BL/6) (n=40) mice were equally divided into group 1A (sham control), group 2A (CLI), group 3A [control-tPA (4.0 mg/kg, intravenously at 3h after CLI)], group 4A (CLI-tPA). Similarly, tPA knock-out (tPA
-/-
) mice (n=40) were equally divided into group 1B (sham control) group 2B (CLI), group 3B [control-tPA (4.0 mg/kg)], group 4B (CLI-tPA). The circulating levels of EPCs (C-kit/CD31+, Sca-1/KDR+, CXCR4/CD34+) were lower in groups 1B and 2B than in groups 1A and 2A, respectively (all p<0.01), and were reversed after tPA treatment (3B vs. 3A or 4B vs. 4A, p>0.05) at 6h and 18h post-CLI. Levels of these biomarkers decreased again 14 days after CLI in tPA
-/-
mice compared to those in wild-type between the respective groups (all p<0.01). Laser Doppler flowmetry showed a higher ratio of ischemic-to-normal blood flow in 2A than in 2B and in 4A than in 4B by day 14 after CLI (all p<0.05). Angiogenesis at protein (CXCR4, SDF-1α, VEGF) and cellular (CXCR4+, SDF-1α +, and CD31+ cells) levels were highest in animals with CLI-tPA, significantly higher in mice with CLI only than in sham controls for both wild-type and tPA
-/-
mice (p<0.01).

Conclusion:
tPA played an essential role in augmenting circulating EPCs, angiogenesis, and blood flow in the ischemic limb in a murine model.

Key words:
tissue plasminogen activator, critical limb ischemia, angiogenesis, circulating endothelial progenitor cells
Abstract 9535: Image-Based Validation of Left Ventricular Mass and Stroke Volume in Fetal Sized Hearts Using 4D Nongated Echocardiography
Authors: Truong Kevin , Mandi Kaavya , Kang Christine , Zhu Meihua , Ashraf Muhammad , Streiff Cole , Sahn David J
Published: April 2024

Background:
The non-gated 4D echocardiogram is the most recently developed tool for visualizing cardiac mechanics without the requisite use of electrocardiogram (EKG) wires. This study was designed to determine the left ventricular (LV) stroke volume (SV) and mass (LVM) of fetal heart models using non-gated 4D echo.

Methods:
4D volumes of fetal heart models (rabbit LVs) were acquired at five different stroke volumes (SV) between 1 and 5mL with an X6-1 matrix transducer interfaced with a Philips® iU22 ultrasound system. Data was collected at two different stroke rates (SR), 40 and 80 strokes per minute, for each SV and analyzed offline with QLab®. LVM and SV were calculated in QLab® according to stacked endocardial and epicardial ellipses and compared to displacement data.

Results:
We found no significant difference between the displacement and 4D echo-derived values for LVM (R
2
=0.98, p<0.01) and SV (R
2
=0.92, p<0.01). It was also determined that 97% of the data was contained within a 95% confidence interval (CI) in a Bland-Altman analysis.

Conclusions:
Thus, we determined that the new Philips® iU22 4D echocardiogram is an accurate way to measure the LV mass and SV of fetal hearts.
Abstract 9549: Influence of Physical Activity on Warfarin Dose, Anticoagulation Response and Risk of Hemorrhagic Complications
Authors: Shendre Aditi , Beasley T. Mark , Brown Todd M , Hill Charles E , Arnett Donna K , Limdi Nita A
Published: April 2024

Importance:
Response to warfarin is influenced by a multitude of patient-specific factors including genetics, clinical comorbidities, and concomitant medications.

Objective:
To determine the influence of consistent physical activity on stable warfarin dose (mg/day), anticoagulation control (percent-time-in-target-range; PTTR) and risk of major hemorrhage among patients on chronic anticoagulation therapy.

Methods:
Physical activity was ascertained by self-report at initiation of warfarin therapy (target INR=2-3) in 1276 patients with changes documented at monthly anticoagulation clinic visits. The association of consistent physical activity (maintained over >80% of visits) on warfarin response and anticoagulation control was evaluated using multi-variable linear regression analysis and for major hemorrhage using survival analysis.

Results:
The number of participants who were consistently physically active (>30 minutes >3 times/week) were 683 (53.7%). Physically active patients required 6.9% higher warfarin doses (p=0.006) and achieved better, although not statistically significant, anticoagulation control (50% vs. 48%; p=0.13) with fewer clinic visits (1.9 vs. 2.5 per patient/ month; p<0.0001) compared to physically inactive patients after accounting for demographic, clinical and genetic factors.

There were 137 major hemorrhagic events encountered over 1801 person years of follow-up (incidence 7.6/100pyrs; 95% CI: 6.4 -8.9). The incidence of hemorrhage was lower among physically active patients (5.6/100pyrs; 95% CI: 4.2-7.2) compared to inactive patients (10.3/100 pyrs; 95% CI: 8.2-12.9; p=0.0004). Active patients had a 38% lower risk of hemorrhage (HR: 0.62, 95% CI: 0.42-0.98, p= 0.03) compared to inactive patients after adjusting for bleeding risk (HAS-BLED score), clinical and genetic factors.

Conclusion and Relevance:
Consistent physical activity is associated with higher warfarin dose requirements but with improved anticoagulation control and lower risk of hemorrhage. In addition to the beneficial effects of physical activity to health and longevity, its influence on drug response needs to be better understood and the mechanisms through which physical activity exerts these effects need to be elucidated.
Abstract 9568: Adipose-Derived Mesenchymal Stem Cells Embedded in Platelet-Rich Fibrin Scaffolds Promote Angiogenesis, Preserve Heart Function, and Reduce Left Ventricular Remodeling in Rat Acute Myocardial Infarction
Authors: Sheu Jiunn-Jye , Chua Sarah , Tsai Tzu -Hsien , Yip Hon-Kan
Published: April 2024

Background:
This study tested the hypothesis that autologous adipose-derived mesenchymal stem cells (ADMSCs) embedded in platelet-rich fibrin (PRF) promotes myocardial regeneration and repair after acute myocardial infarction (AMI).

Methods and Results:
Adult male Sprague-Dawley rats equally divided (n=10/group) into group 1 (sham-operated), group 2 (AMI by ligating left coronary artery), group 3 (AMI+PRF), and group 4 (AMI+PRF-embedded autologous ADMSCs) were sacrificed on day 42 after AMI. Left ventricular (LV) dimension, infarct/fibrotic areas, and distance between I bands were lowest in group 1, highest in group 2, higher in group 3 than in group 4, whereas LV performance and wall thickness exhibited a reversed pattern (p<0.001). Protein expressions of inflammatory (MMP-9, IL-1β), oxidative, apoptotic (Bax, cleaved-PARP), fibrotic (Smad 3, TFG-β), hypertrophic (β-MHC), and heart failure (BNP) biomarkers displayed an identical pattern in infarct/fibrotic areas, whereas protein expressions of anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), anti-fibrotic (Smad1/5, BMP-2) biomarkers, and α-MHC showed an opposite pattern (p<0.01). Angiogenic activities (Small-vessel numbers; C-kit+, Sca-1+, CD31+, SDF-1α+, CXCR4+ cells; protein expressions of SDF-1α, CXCR4, VEGF) were highest in group 4 and lowest in group 1, higher in group 3 than in group 2 (p<0.001).

Conclusion:
ADMSCs embedded in PRF offered significant benefit in preserving LV function after AMI.
Abstract 9570: Adenosine Triphosphate Facilitates Dormant Conduction across Left Atrial Lines in Patients With Atrial Fibrillation Who Underwent Catheter Ablation
Authors: Hama Yoshiyuki , Matsudo Yuji , Kuwahara Taishi , Fujimaki Haruka , Tokimasa Satoshi , Katsu Bi , Tanaka Shuzo , Tonoike Norimasa , Hou Kyokushi , Sekine Tai , Yamamoto Masashi , Himi Toshiharu
Published: April 2024

Introduction:
The addition of left atrial lines including a roof line, bottom line, and mitral isthmus line after pulmonary vein (PV) isolation may lead to a favorable outcome of atrial fibrillation (AF) ablation. Transient reconduction of the isolated pulmonary vein (PV) is induced by administration of adenosine triphosphate (ATP) and elimination of dormant conduction improves outcome of AF ablation. The potential role of ATP in other arrhythmic substrates, such as left atrial lines, remains unclear. The aim of this study was to investigate the characteristics and frequency of dormant left atrial line conduction.

Methods:
Sixty-four patients (50 men; mean age 65±10; 3 paroxysmal, 26 persistent, 35 Longstanding persistent) who underwent first ablation of left atrial lines were enrolled in this study. A roof line, bottom line and mitral isthmus line were performed in 63 patients, 44 patients and 64 patients, respectively. Irrigated ablation catheters were used through steerable sheaths with a max power of 35W at the endocardial surface and 30W in the coronary sinus. ATP (20mg) was given greater than 10 minutes after completion of left atrial lines to reveal dormant conduction.

Results:
Completion of a roof line, bottom line and mitral isthmus line was achieved in 97% (61/63), 98% (43/44), and 95% (61/64), respectively. Following administration of ATP, dormant conduction was observed in 3.2% at a roof line, 2.3% at a bottom line, and 3.2% at a mitral isthmus line. Persistent reconduction was observed in 1.6% at a roof line and 2.3% at a bottom line. Transient reconduction was observed in 1.6% at a roof line and 3.2% at a mitral isthmus line. Following additional ablation, dormant left atrial line conduction was eliminated in all patients. The frequency of dormant left atrial line conduction was similar to that of dormant PV conduction (6.3% vs 7.8%., P=0.7)

Conclusion:
Administration of ATP could reveal dormant left atrial line conduction. Dormant conduction was evenly induced among PVs and left atrial lines.
Abstract 9578: Normal Ranges of Right Ventricular Strain in Children: A Systematic Review and Meta-Analysis
Authors: Levy Philip T , Sanchez-Mejia Aura A , Fowler Susan , Holland Mark R , Singh Gautam K
Published: April 2024

Background:
Establishment of the range of normal values and associated variations of two-dimensional speckle-tracking echocardiography (2DSTE) derived right ventricular (RV) strain is a prerequisite for its routine clinical application in children. The objectives of this study were to perform a meta-analysis of normal ranges of RV longitudinal strain measurements derived by 2DSTE in children and identify confounders that may contribute to differences in reported measures.[[Unable to Display Character:   ]]

Methods:
A systematic review was launched in PubMed, Embase, Scopus, and Cochrane. Search hedges were created to cover the concepts of pediatrics, speckle-tracking, and right ventricle. Two investigators independently identified and included studies if they reported the 2DSTE derived RV strain measures: RV global longitudinal strain (GS), systolic strain rate (GSRs), early diastolic strain rate (GRSe), late diastolic strain rate (GSRa), or segmental LS at the apical, mid, and basal ventricular levels in healthy children. The weighted mean was estimated by using random-effects with 95% confidence intervals (CI), heterogeneity was assessed by the Cochran’s Q statistic and the inconsistency index (I2), and publication bias was evaluated by funnel plots and the Egger test. Effects of demographic, clinical, and equipment/software variables were assessed in a meta-regression.[[Unable to Display Character:   ]]

Results:
The search identified 229 children from 10 studies. Normal values varied for GS from -21% to -34% (mean -29%, CI, -32% to -27%), GSRs from -1.3 to -2.4 (mean -1.9, CI, -2.1 to -1.6), GSRe from 1.7 to 2.7 (mean, 2.3, CI, 2.0 to 2.7), and GSRa from 1.0 to 1.3 (mean, 1.2, CI, 1.04 to 1.3). A significant base-to-apex segmental strain gradient (p <0.05) was observed in the RV free wall. There was significant between-study heterogeneity and inconsistency (I2>89% and p<0.01 for each strain measure), which was not explained by age, gender, body surface area, heart rate, frame rate or equipment/software. The meta-regression showed that these effects were not significant determinants of variations among normal ranges of strain values. There was no evidence of publication bias (Egger, p=0.6).[[Unable to Display Character:   ]]

Conclusions:
This study is the first to define normal values of RV strain in children on the basis of a meta-analysis.
Abstract 9602: Cystathionine ?-lyase/hydrogen Sulfide Metabolism Regulates Endothelial Progenitor Cell Mediated Vasculogenesis During Ischemic Vascular Remodeling
Authors: Kolluru Gopi K , Bir Shyamal C , Shen Xinggui , Elrod John W , Wang Rui , Lefer David , Kevil Christopher G
Published: April 2024

Introduction:
H2S is a gaseous signaling molecule primarily produced in the vasculature by Cystathionine γ-lyase (CGL/CSE) enzyme, that regulates many biological functions including vasodilation, anti-inflammation, cytoprotection and angiogenesis. CSE genetic deficiency and subsequent reduction in H2S levels attenuates ischemic vascular remodeling. However, effects of CSE/H2S in relation to vasculogenesis have not been investigated.

Objective:
To investigate the effect of endothelial specific CSE (EC-CSE) transgenic overexpression in restoring blood flow and vasculogenesis in the ischemic hind limb model.

Methods:
Unilateral femoral artery ligation was performed in wild type (WT), CSE-/- and EC-CSE mice, treated with PBS or H2S donor, DATS (n=8-10, in each group). Tissue angiogenic and proliferation indices were determined by the ratios of CD31/DAPI and Ki67/DAPI staining respectively. Expression of CSE and SDF-1 in the ischemic and non-ischemic limbs was determined by immunohistochemistry; CSE and HIF-1α were measured by qRT-PCR; and ELISA to measure VEGF levels. Plasma and tissue sulfide levels were measured using the MBB/HPLC method. Flow cytometry was used to analyze bone marrow-derived, blood and skeletal muscle EPCs positive for CD34/FLK-1 staining.

Results:
Ischemic hind limb perfusion was significantly impaired in CSE-/- compared to WT mice, while blood flow was restored in DATS treated cohort groups and EC-CSE transgenic mice by day 14. Angiogenic and proliferation indices were decreased in CSE-/- mice, and restored by DATS treatment and in EC-CSE transgenic mice. These findings corresponded with significantly increased circulating EPCs at days 3, 5 and 7 upon DATS treatment and EC-CSE transgenic overexpression. Lastly, we observed that CSE/H2S induces EPC recruitment via SDF-1/VEGF mediated pathways that augments vasculogenesis and restoration of ischemic hind limb blood flow.

Conclusion:
Endothelial specific overexpression of CSE (EC-CSE) and exogenous H2S delivery reversed impaired blood flow in CSE-/- mice through EPC mediated revascularization during hind limb ischemia. Modulation of CSE mediated H2S induced revascularization might serve as a novel therapeutic approach for ischemic vascular remodeling.
Abstract 9623: Stimulatory Effects of Cardiotrophin-1 on Atherosclerosis
Authors: Watanabe Takuya , Konii Hanae , Kikuchi Sayaka , Okiyama Hazuki , Watanabe Rena , Hasegawa Akinori , Yamamoto Keigo , Sato Kengo , Itoh Fumiko , Hirano Tsutomu
Published: April 2024

Cardiotrophin-1 (CT-1), a cytokine belonging to the interleukin-6 superfamily, was recently shown to be expressed in the intima of early atherosclerotic lesions in the human carotid artery. CT-1 stimulates pro-atherogenic molecule expression in human vascular endothelial cells (EC) and monocyte migration. However, it has not been reported whether CT-1 accelerates atherosclerosis. This study was performed to examine the stimulatory effects of CT-1 on human macrophage foam cell formation, human EC proliferation, and the migration and proliferation of human vascular smooth muscle cells (VSMCs) in vitro, and on the development of atherosclerotic lesions in apolipoprotein E-deficient (ApoE-/-) mice in vivo. CT-1 was expressed at high levels in ECs and macrophages in both humans and ApoE-/- mice. CT-1 significantly enhanced oxidized low-density lipoprotein-induced foam cell formation associated with increased levels of CD36 and acyl-CoA:cholesterol acyltransferase-1 (ACAT1) expression in human monocyte-derived macrophages. CT-1 also significantly stimulated the migration and proliferation of human aortic VSMCs, but not EC proliferation. Four-week-infusion of CT-1 into ApoE-/- mice significantly accelerated the development of aortic atherosclerotic lesions with increased monocyte/macrophage infiltration and VSMC content in the aortic wall. Activation of inflammasome, such as apoptosis-associated speck-like protein containing a caspase recruitment domain, nuclear factor-κB, and cyclooxygenase-2, was observed in exudate peritoneal macrophages from ApoE-/- mice infused with CT-1. Infusion of anti-CT-1 neutralizing antibody alone into ApoE-/- mice significantly suppressed monocyte/macrophage infiltration in atherosclerotic lesions. These results indicate that CT-1 accelerates the development of atherosclerotic lesions by stimulating the inflammasome and foam cell formation associated with CD36 and ACAT1 up-regulation in macrophages and VSMC migration and proliferation, contributing to the occurrence of atherosclerotic vascular diseases. Blockade of cardiotrophin-1 is expected to emerge as a new line of therapy against atherosclerosis and its related diseases.
Abstract 9632: Mitral Regurgitation and Atrial Fibrillation: Is it Worth Cardioverting?
Authors: Qintar Mohammed , Hammadah Muhammad , Thomas James , Chung Mina
Published: April 2024

Background:
Atrial fibrillation (AF) presents in 30%-40% of patients presenting for mitral regurgitation (MR) surgery but may contribute to functional MR. Although severe MR often inhibits consideration of cardioversion (CV), restoring sinus rhythm (SR) or rate control might yield benefits. We tested the hypothesis that in patients with 3-4+MR, restoring and maintaining SR after CV can significantly improve MR to non-surgical ranges (≤2+MR).

Methods:
From a prospectively collected database of CV procedures, we retrospectively identified patients undergoing their first CV with an echo within 1 year showing moderately severe to severe 3-4+MR and with a follow-up echo within 1 year after CV. Their CV had to be successful. Of 9333 patients undergoing first CVs, 433 met inclusion criteria. Patients with intervening valve surgery were excluded. The primary outcome was reduction in MR to ≤2+. Paired t-tests were used to analyze changes in MR, LVEF, and TV. Echocardiographic and clinical predictors of improvement were determined using multivariate regression models.

Results:
Paired t-tests showed improvement in MR irrespective of rhythm during follow up, although greater improvement was observed in patients with SR vs AF at follow up (mean pair change (MPC) 0.83 ± 1.05, 95% CI 0.616-1.054, p<0.001 vs 0.47 ± 0.90, 95% CI 0.212-0.727, p=0.001, respectively). 55% of patients with 3-4+MR had no more than moderate (2+) residual MR at follow-up if they maintained sinus rhythm compared to 38% in patients with recurrence of atrial fibrillation (Figure, p=0.033). LVEF and TR also improved with maintenance of sinus rhythm (Figure).

Conclusion:
Despite moderately severe to severe MR at baseline, clinically significant improvement in MR was observed after successful CV, especially with maintenance of sinus rhythm at follow up.