bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9324: Safety and Efficacy of Device Closure for Patent Foramen Ovale for Secondary Prevention of Neurological events. Meta-analysis of Randomized Controlled Trials
Authors: Hakeem Abdul , Marmagkiolis Konstantinos , Hacioglu Yalcin , Uretsky Barry F F , Gundogdu Betul , Leesar, Massoud , Bailey Steven R , Cilingiroglu Mehmet
Published: April 2024

Background:
While the prevalence of patent foramen ovale (PFO) is significantly higher in patients with cryptogenic stroke, considerable controversy persists regarding the best management of such patients. We performed a meta-analysis of randomized controlled trials comparing PFO closure with medical therapy.

Methods:
A prospective protocol (Protocol registration # CRD42013004197) was developed and registered using the following data sources: PubMed, Cochrane Register of Controlled Trials, conference proceedings, and internet-based resources of clinical trials. Primary analyses were performed using the intention-to-treat method as reported in the respective trials

Results:
Three randomized trials comparing percutaneous PFO closure vs. medical therapy for secondary prevention of embolic neurological events involving 2303 participants (1153 medical therapy, 1150 PFO closure) formed the data set. Two trials (RESPECT and PC) used the Amplatzer PFO occluder whereas the Starflex closure device was used in the CLOSURE 1 trial. Baseline characteristics were similar. Mean age was 46 years. The prevalence of atrial septal aneurysm was similar (approximately 34% in both groups). During long-term follow-up , the pooled incidence of the primary endpoint (composite of stroke, death, or fatal stroke) was 3.4 % in the PFO closure arm and 4.8% in the medical therapy group [risk reduction (RR) 0.71 (0.48-1.06); p=0.09] The incidence of recurrent neurological events (secondary endpoint) was 1.7% for PFO closure and 2.7% for medical therapy[ RR 0.66 (0.35,1.24), p=0.19]. There was no difference in terms of death or adverse events between the two groups. After transcatheter closure, recurrent neurological events did not seem to be related to pre-treatment shunt size or atrial septal aneurysm. Reduction in primary event rate with closure strategy (in comparison to medical therapy) almost reached statistical significance (P=0.05) in male patients.

Conclusions:
While this meta-analysis of randomized clinical trials demonstrated no statistical significance in comparison to medical therapy, there was a strong trend towards overall improvement in outcomes in the PFO closure group.
Abstract 9366: Generation of Human Embryonic Stem Cell-Derived Cardiac Progenitors: Is the Risk of Teratoma Still A Clinically Relevant Roadblock ?
Authors: Vanneaux Valérie , Bel Alain , Nematalla Hany , Garcia Sylvie , Bellamy Valérie , Périer Marie-Cécile , Robidel Estelle , Tosca Lucie , Fabreguettes Jean-Roch , Trouvin Jean-Hugues , Tachdjian Gérard , Hagége Albert A , Bruneval Patrick , Larghero Jérôme , Menasché Philippe
Published: April 2024

Background:
The risk of teratoma is a major limitation to a safe clinical use of human embryonic stem cells (ESC) for heart repair.We developed a straightforward and clinically usable method for generating ESC-derived cardiac progenitors and assessed its safety
in vitro
and in animal models.

Methods:
Human ESC (I6 line) were treated for 4 days by bone morphogenetic protein (BMP)-2 in an insulin-free medium. Taking CD15 as a marker for cell differentiation, the lineage-directed population was immunomagnetically sorted and assessed for purity (flow cytometry), genetic stability (caryotype, FISH focused on chromosomes 12, 17, and 20 and 105K oligonucleotide-based array CGH) and phenotype (transcriptome). For
in vivo
testing, 58 nude rats underwent a myocardial infarction and, 4-6 weeks later, received a CD15
+
-loaded fibrin patch overlaying the infarct area (n=26), a cell-free fibrin patch (controls; n=16) or were sham-operated (n=16). In addition, 54 immunodeficient RAG2-/- γc-/- C5-/- mice were subcutaneously injected with CD15
+
cells, undifferentiated ESC, CD15
+
cells spiked with different ratios of undifferentiated ESC or 100% CD15-negative cells.

Results:
The mean ± SD purity rate of the sorted CD15
+
population was 96.2 ± 1.8% (average of 25 preclinical runs). These cells were genetically stable with gene polymorphisms considered usual in the human species and expressed cardiac markers, predominantly Isl-1. After 3 months of follow-up, none of the nude rats treated with the CD15
+
-loaded fibrin patch had developed a teratoma and monthly echocardiograms showed that they yielded the highest values of LVEF (
p
<0.003
vs
baseline) and the smallest degree of remodeling compared to control or sham-operated rats. Likewise, while mice receiving undifferentiated ESC developed teratomas within 6 months post-injections, none of those (n=12) injected with the CD15
+
cells presented a teratoma or an extra-cardiac tumor (maximal follow-up: 7 months). The CD15-negative population was not tumorigenic either (0/8).

Conclusion:
This CD15
+
progenitor cell population had an overall reassuring safety profile, suggesting that our process of lineage commitment and purification may represent an efficient translational step towards a safe clinical use of these cells.
Abstract 9400: Obesity is Associated With Lower Mortality in Patients With Implantable Cardioverter-Defibrillator
Authors: Mirza Mahek , Yeneneh Beeletsega , Strunets Anton , Cho Chi , Choudhuri Indrajit , Mortada M. Eyman , Nangia Vikram , Bhatia Atul , Niazi Imran , Sra Jasbir , Jahangir Arshad
Published: April 2024

Introduction:
Higher body mass index (BMI) is associated with increased cardiovascular risk factors. Recent studies indicate an inverse relationship between obesity and overall survival after acute cardiovascular events. However, in patients at high risk of sudden cardiac death (SCD), the impact of obesity on mortality is not defined.

Hypothesis:
We assessed whether a paradoxical relationship between BMI and risk of overall mortality is present in patients with an implantable cardioverter-defibrillator (ICD).

Methods:
Consecutive patients who received an ICD for prevention of SCD at our institution from January 2010 to December 2011 were retrospectively divided into three groups based on BMI. Clinical parameters and long-term outcomes as determined by Kaplan-Meier and logistic regression models were compared among normal (BMI <25), overweight (BMI 25-29.9) and obese (BMI ≥30) groups.

Results:
Of 1,151 patients (mean age 67 ± 13 years; 67% male), 26% had normal BMI, 32% were overweight and 42% were obese. There were no significant baseline differences in mean left ventricular ejection fraction (30 ± 12%), type of ICD implanted or indication for implantation, prior syncope or cardiac arrest, and prevalence of heart failure or atrial fibrillation. Patients with normal BMI were older (68 ± 14 years) compared with the overweight (68 ± 13 years) and obese (62 ± 12 years) groups (p<0.001). Despite significantly higher prevalences of diabetes, hypertension, ischemic heart disease and prior myocardial infarction, the higher BMI groups had lower overall mortality than the normal BMI group. Median time to death after ICD implantation also was significantly shorter in the normal BMI group (figure). On multivariate logistic regression analysis, higher BMI (including obese and overweight groups) was protective against mortality.

Conclusion:
Patients with an ICD who were obese or overweight had lower mortality than those with normal BMI.
Abstract 9405: Lower Achieved Systolic Pressure (=130 mm Hg) is Associated With a Decreased Risk of New Atrial Fibrillation in Hypertensive Patients With Electrocardiographic Left Ventricular Hypertrophy: The LIFE Study
Authors: Okin Peter M , Hille Darcy A , Larstorp Anne Cecilie K , Wachtell Kristian , Kjeldsen Sverre E , Dahlöf Björn , Devereux Richard B
Published: April 2024

Background:
There is a well-established association between hypertension and atrial fibrillation (AF), with recent studies demonstrating that even upper normal systolic blood pressures (SBP) are long-term predictors of incident AF. These findings suggest that more aggressive control of BP may reduce the risk of new AF. However, whether more aggressive reduction of SBP is associated with a lower incidence of AF remains unclear.

Methods:
Risk of new-onset AF was examined in relation to last in-treatment SBP prior to AF diagnosis or last in-study measurement in the absence of new AF in 8831 hypertensive patients with ECG LVH with no history of AF, in sinus rhythm on their baseline ECG, randomly assigned to losartan- or atenolol-based treatment. Patients with in-treatment SBP ≤130 mm Hg (lowest quintile at last measurement) and SBP between 131 and 141, were compared with patients with in-treatment SBP ≥142 (median SBP at last measurement).

Results:
During 4.6±1.1 years follow-up, new-onset AF was diagnosed in 701 patients (7.9%). In univariate analyses, compared with in-treatment SBP ≥142, in-treatment SBP ≤130 entered as a time-varying covariate was associated with a 46% lower risk (95% CI 31-58%) and in-treatment SBP between 131 and 141 with the same 46% lower risk (95% CI 35-55%) of developing AF. After adjusting for randomized treatment, age, sex, race, diabetes, history of ischemic heart disease, MI or heart failure, prior antihypertensive therapy, baseline serum glucose, creatinine, HDL and total cholesterol entered as standard covariates, and for incident MI, heart failure and in-treatment Cornell product LVH, heart rate, diastolic BP and HDL treated as time-varying covariates, achievement of a SBP ≤130 remained associated with a 40% lower risk (95% CI 18-55%) and in-treatment SBP of 131 to 141 with a 24% lower risk (95% CI 7-38%) of new AF.

Conclusions:
Achieved SBP ≤130 is associated with a lower risk of developing new-onset AF in hypertensive patients with ECG LVH, independent of other known and possible risk factors for AF. Further study will be needed to determine whether targeting hypertensive patients without AF to lower SBP goals can reduce the burden of new AF in this high-risk population.
Abstract 9446: Periodic Acceleration (pGz) Preserves Heart Rate Variability After Cardiac Arrest
Authors: Adams Jose A , Uryash Arkady , Kurlansky Paul
Published: April 2024

Heart Rate Variability (HRV) and lack thereof is important in predicting neurological outcome after brain injury and cardiac arrest (CA). The post CA period has decreased HRV compared to pre-arrest, and interventions such hypothermia may preserve HRV. Periodic acceleration (pGz) the sinusoidal head to foot motion of the supine body with a motion platform increases endothelial derived NO (eNO) and neuronal nitric oxide (nNOS) in heart via pulsatile shear stress, and preconditions from global and focal ischemia reperfusion injury (I/R). NO has a facilitator role on vagal chronotropism and inhibition of nNOS reduces HRV. CA is a model of whole body I/R. This study tests whether pGz applied prior to whole body I/R preserves HRV in a pig model of CA. Fourteen male swine (40-50lbs) were anesthetized, intubated and instrumented to measure EKG and hemodynamics. They were placed on a motion platform and randomized to 1 hr of pGz (180 cpm and Gz ± 0.4) or none control (C). VF was electrically induced and unsupported for 8 min, followed by chest compression and defibrillation until return of spontaneous circulation (ROSC) or 10 min. Short term HRV (excluding ectopic beats) was measured including; time domain; SDNN (standard deviation of normal to normal intervals), RMSSD (square root of the mean squared differences of successive normal to normal intervals) and frequency domain, at baseline (BL1), after pGz or C (BL2) and 30, to 180 mins after ROSC (ROSC30, 60,120,180 ). All animals had ROSC after a median of 4 defibrillation attempts. There were no differences between groups in defibrillation attempts, time to ROSC, arterial blood gases or hemodynamics over time. pGz animals had less hemodynamically significant arrhythmias in the first 30 mins ROSC; C (35) vs pGz (7) (p< 0.05) Data mean ±SEM * p < 0.05 C vs pGz. pGz applied prior to I/R in addition to being cardioprotective preserves HRV and is a novel non invasive method to preserve autonomic nervous system output and precondition the myocardium.
Abstract 9449: Feasibility and Accuracy of High Resolution 4D Echocardiography for Evaluation of Left Ventricular Mass and Stroke Volume: An in vitro Phantom Study
Authors: Streiff Cole , Panosian Jill , Zhu Meihua , Lie Glenn R , Hansen Gunnar , Ashraf Muhammad , Sahn David J
Published: April 2024

Background:
This study was designed to determine the accuracy and feasibility of a new 4D echo-based semi-automated quantification of left ventricular (LV) mass (LVM) and stroke volume (SV) in an
in vitro
phantom model.

Methods:
Ten freshly harvested adult pig and sheep hearts (147-326 grams) were passively driven using a pulsatile pump to simulate normal cardiac motion. Each heart was pumped at 3 stroke rates (SR) (40, 65, and 85 strokes/min) and 3 SVs (30, 50, and 70 ml at each SR). Full-volume 4D cine loops were collected with a 3V Matrix transducer interfaced with a GE Vivid E9 ultrasound system at a maximized frame rate (≥25 FPS) using multi-beat acquisition. Images were analyzed offline using EchoPAC PC for semi-automated quantification of SV and LVM and compared to displacement values.

Results:
No significant differences were detected between the values of either SV or LVM at different stroke rates (P=0.99). Data showed excellent linear correlation between 4D echo-derived SV and LVM, and displacement data (SV: R
2
=0.96, p<0.001; LVM: R
2
=0.99, p<0.001). Bland-Altman analyses revealed 98% and 99% of points within a 95% CI for SV and LVM respectively. Interobserver variability was shown to be excellent (SV: R
2
=0.92, p<0.001; LVM: R
2
=0.99, p<0.001).

Conclusions:
4D echo-based quantification may be an accurate and feasible method for determination of LV mass and stoke volume and a physiologically relevant range of stroke volumes and stroke rates.
Abstract 9452: Comparative Study of Adipose Derived Regenerative Cells versus Bone Marrow-Mononuclear Cells for Therapeutic Angiogenesis
Authors: Hao Chang-ning , Shintani Satoshi , Shimizu Yuuki , Wu Hong-xian , Kondo Kazuhisa , Ishii Masakazu , Murohara Toyoaki
Published: April 2024

Objective:
Due to the poor prognosis of therapeutic angiogenesis by bone marrow-mononuclear cells (BM-MNCs) to severe atherosclerotic patients, we focused on adipose-derived regenerative cells (ADRCs) as an alternative choice. Here, we compared the therapeutic efficacy between these two cells in two animal models of hindlimb ischemia (HLI) and further tested the hypothesis that ADRC augments angiogenesis by regulating local hemostasis through macrophage polarization.

Methods and Results:
We observed that fluorescence labeled ADRCs incorporated into vasculature in vitro and vivo. Then, we compared the paracrine manner between ADRCs and BM-MNCs using conditioned media (CM). Accelerated migratory ability and prevented apoptosis of human umbilical vein endothelial cells (HUVECs) were observed treated by both CM compared with control. In vivo study, implantation of either ADRCs or BM-MNCs revealed more angiographically detectable collateral vessels formation, higher capillary density, greater cuff blood pressure ratio, and stronger laser Doppler blood perfusion signals than control in rabbit HLI model. In mice study, we proved ADRCs changed the polarity of infiltrated macrophage into M2 phenotype through prostaglandin E2 (PGE2) and EP2/4 receptors. Next, the mRNA expression of several angiogenic cytokines were up-regulated in the macrophages cultured in ADRC-CM compared with BM-MNC-CM. ADRCs implantation also muted local inflammation and apoptosis via down-regulating the gene expression of pro-inflammatory cytokines, as well as increasing interleukin (IL)-10. Finally, blockade of IL-10 by neutralizing monoclonal antibody resulted in harsher microenvironment and attenuated ischemic-induced angiogenesis in mouse HLI model.

Conclusions:
In conclusion, the safety and efficacy of therapeutic angiogenesis by ADRCs implantation was comparable with BM-MNCs in rabbit HLI model. Moreover, slanted M2 polarity of infiltrated macrophages was observed after ADRCs implantation through PGE2 - EP2/4 - IL-10 axis, leading to facilitation of postnatal neovascularization via their angiogenic, anti-inflammatory and anti-apoptotic manners.
Abstract 9454: Arterial Baroreflex Dysfunction Impairs Angiogenesis in Response to Hindlimb Ischemia
Authors: Hao Chang-ning , Huang Zhen-hao , Song Shu-wei , Shi Yi-qin , Cheng Xian-wu , Murohara Toyoaki , Su Ding-feng , Duan Jun-li
Published: April 2024

Objective:
We examined whether ischemia-induced angiogenesis was reduced by the arterial baroreflex (ABR) dysfunction, and if so, we further examined whether the reduced angiogenesis was associated with a reduction of endothelium-derived acetylcholine (Ed-ACh) release using a rat model of hindlimb ischemia (HLI). We also determined whether this effect would be restored by the administration of pyridostigmine (Pyr), a cholinesterase inhibitor.

Methods and Results:
Male Sprague-Dawley rats were randomly assigned to 3 groups that received 1) sham operation (control), 2) sinoaortic denervation (SAD)-induced ABR dysfunction, 3) SAD rat diet with Pyr. 4 weeks after the SAD intervention, HLI was surgically induced in all groups. Infrared spectrum analyses showed that the recovery of the ischemic/normal limb temperature ratio in the SAD rats remained impaired throughout the follow-up period. At postoperative day 14, immunohistochemical analyses in the ischemic limb revealed significantly lower capillary densities in the SAD group than in the control, which were associated with decreased tissue expression of choline acetyltransferase (ChAT) and acetylcholine transporter (AChT). Pyr significantly improved the temperature ratio and capillary densities, accompanied by elevation of ChAT and AChT protein in the ischemic muscles. Interestingly, Pyr not only elevated the levels of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) proteins of ischemic muscles but also improved functional recovery following hindlimb ischemia in α7-nicotinic ACh receptor (α7-nAChR) knockout mice. Furthermore, in vitro, acetylcholine analogue (carbachol) stimulated the expression of VEGF and phosphorylation of VEGF receoptor-2 (VEGFR2) in umbilicus vein endothelial cells, and these changes were diminished by methyllycaconitine, a nicotinic receptor blocker.

Conclusions:
These findings suggest that the ABR dysfunction likely triggers and impairs angiogenesis in response to ischemia and that the Pyr-mediated augmentation of tissue Ed-ACh activity stimulates VEGF expression and VEGFR2 phosphorylation by the α7-nAChR-dependent/-independent activation of the Pyr, thereby improving vascular angiogenic action.
Abstract 9463: Clinical and Genetic Evidence for Angiotensin Converting Enzyme Inhibition to Prevent Postoperative Tachyarrhythmias After Congenital Heart Surgery
Authors: Smith Andrew H , Flack English C , Borgman Kristie Y , Owen Jill P , Fish Frank A , Bichell David P , Kannankeril Prince J
Published: April 2024

Background:
The common insertion/deletion polymorphism in the gene encoding angiotensin-converting enzyme (ACE I/D) has been described in association with tachyarrhythmias. We prospectively examined the role of this polymorphism in a large cohort of pediatric patients undergoing congenital heart surgery with cardiopulmonary bypass (CPB).

Methods:
Subjects undergoing congenital heart surgery at our institution were consecutively recruited and enrolled from September 2007 through December 2012. In addition to DNA, demographic and perioperative clinical data were obtained from all subjects.

Results:
Over the study period, 886 subjects undergoing congenital heart surgery with CPB were enrolled. Postoperative tachyarrhythmias were documented in 45% of patients, most commonly ventricular tachycardia (16%), junctional ectopic tachycardia (11%), and atrial tachycardia (10%). Postoperative tachyarrhythmias were associated with prolonged mechanical ventilation (p<0.001) and ICU length of stay (p<0.001). ACE I/D was in Hardy-Weinberg equilibrium (19% I/I, 49% I/D, 32% D/D). Tachyarrhythmias were noted in 47% of index cases with I/D or D/D genotypes, relative to 36% of cases with an I/I genotype (p=0.01). Presence of the I/D or D/D genotype was associated with a 60% increase in odds of new tachyarrhythmia (OR 1.6, 95%CI 1.1-2.3, p=0.02), independent of significant univariate predictors. While preoperative ACE inhibitor administration was independently associated with a 47% reduction in odds of postoperative tachyarrhythmia in the entire cohort (OR 0.53, 95%CI 0.32-0.88, p=0.01), this reduction was driven primarily by a five-fold reduction in tachyarrhythmias among patients with the I/I genotype (OR 0.19, 95% CI 0.04-0.88, p=0.02).

Conclusions:
The risk of tachyarrhythmias after congenital heart surgery is affected by the ACE I/D polymorphism, independent of other known risk factors. Preoperative ACE inhibition is associated with a lower risk of postoperative tachyarrhythmias, and this antiarrhythmic effect appears genotype dependent. Given the associated morbidity of postoperative arrhythmias, an understanding of genotype variation may play an important role in the perioperative management of congenital heart surgery.
Abstract 9562: Liver Dysfunction Assessed by Model of End-stage Liver Disease Excluding INR (MELD-XI) Scoring System Predicts Adverse Prognosis in Heart Failure
Authors: Shimizu Takeshi , Yoshihsa Akiomi , Takiguchi Mai , Yamauchi Hiroyuki , Owada Takashi , Iwaya Shoji , Miyata Makiko , Sato Takamasa , Suzuki Satoshi , Oikawa Masayoshi , Kobayashi Atsushi , Yamaki Takayoshi , Sugimoto Koichi , Kunii Hiroyuki , Nakazato Kazuhiko , Suzuki Hitoshi , Saitoh Shu-ichi , Takeishi Yasuchika
Published: April 2024

Background:
Liver dysfunction due to end-stage heart failure (HF) is often referred as cardiac or congestive hepatopathy. The composite Model for End-Stage Liver Disease excluding INR (MELD-XI) is a robust scoring system of liver function, and a high score is associated with poor prognosis in heart transplant recipients. However, the impact of MELD-XI scores on cardiac function and prognosis in general HF patients still remains unclear.

Methods and Results:
We retrospectively analyzed 550 patients with HF who admitted to our hospital. Liver function was estimated by MELD-XI formula (5.11хlog (bilirubin)+ 11.76хlog (creatinine)+9.44). These patients were divided into two groups based on the median MELD-XI score: Group L (MELD-XI <10, n=269) and Group H (MELD-XI ≥10, n=281). We compared echocardiographic findings and cardiac event rates including cardiac deaths and re-hospitalization due to worsening HF between two groups. In echocardiographic paremeters, left atrial volume (LAV), right atrial area (RAA), right ventricular diastolic area (RVAd), right ventricular systolic area (RVAs), inferior vena cava diameter (IVC) were higher, and left ventricular ejection fraction (LVEF) was lower in group H than in group L (LAV: 93.7 vs. 74.0 ml, RAA: 25.0 vs. 16.5 cm
2
, RVAd: 17.1 vs. 15.7 cm
2
, RVAs: 10.6 vs. 9.1 cm
2
, IVC: 15.9 vs. 14.4 mm, LVEF: 45.5 vs. 50.4%, P<0.05, respectively). Right ventricular fractional area change did not differ between 2 groups. In addition, 151 events (52 deaths and 99 re-hospitalizations) occurred during the follow-up period (mean 348 days). Importantly, the event-free rate was significantly higher in group L than in group H (78.4% vs. 66.9%, logrank
P
=0.001). In the Cox proportional hazard analysis, higher MELD-XI (MELD-XI ≥10) was an independent predictor of cardiac events in HF patients (hazard ratio 1.79, 95% confidence interval 1.29-2.49, P=0.001).

Conclusions:
A MELD-XI scoring system, a marker of liver function, can identify high risk patients associated with larger right heart volume overload, left ventricular systolic dysfunction, and adverse clinical outcomes in HF.
Abstract 9563: High-frequency QRS Analysis is More Specific and Accurate Than Conventional ST-segment Analysis in Diagnosing Coronary Ischaemia
Authors: Chan Ngai Y , Chow Hoi F , Yuen Ho C , Chu Pui S , Lau Suet T , Tsui Ping T , Choy Chi C , Lau Chun L , Lo Ying K , Mok Ngai S
Published: April 2024

Purpose:
High-frequency QRS analysis (HFQRS) is a new tool for detecting stress-induced coronary ischaemia. This study aims to compare HFQRS with conventional ST-segment analysis (STA) in the diagnostic performance in patients with chest pain and no history of coronary artery disease, which has not been investigated before.

Methods:
One hundred and seventy-five patients (120 men; mean age 58.2±7.5) with chest pain referred for diagnostic workup of coronary ischaemia were recruited. They underwent symptom-limited exercise treadmill test with both HFQRS and STA, followed by myocardial perfusion imaging (MPI) to confirm presence or absence of ischaemia.

Results:
Coronary ischaemia was present in 20 (11.4%) patients by MPI. HFQRS was more specific (85.8 vs 68.4%; p=0.002) and similarly sensitive (45 vs 60%; p=0.371) compared with STA. HFQRS had a higher positive predictive value (29 vs 19.7%; p=0.01) and similar negative predictive value (92.4 vs 93%; p=0.61) compared with STA. The diagnostic accuracy for coronary ischaemia by HFQRS was significantly higher than STA (81.1 vs 67.4%; p=0.001).

Conclusions:
HFQRS is more specific and accurate than STA in diagnosing coronary ischaemia in patients with chest pain and no prior history of coronary artery disease.
Abstract 9567: Melatonin Treatment Improves Adipose-derived Mesenchymal Stem Cell Therapy for Acute Lung Ischemia-reperfusion Injury
Authors: Chua Sarah , Tsai Tzu -Hsien , Sheu Jiunn-Jye , Yip Hon-Kan
Published: April 2024

Background:
This study investigated whether melatonin-treated adipose-derived mesenchymal stem cells (ADMSC) offered superior protection against acute lung ischemia-reperfusion (IR) injury.

Method and Results:
Adult male SD rats (n=30) were randomized equally into 5 groups: sham controls, lung IR-saline, lung IR-melatonin, lung IR-melatonin-normal ADMSC, and lung IR-melatonin-apoptotic ADMSC. Arterial oxygen saturation was lowest in lung IR-saline; lower in lung IR-melatonin than sham controls, lung IR-melatonin-normal ADMSC, and lung IR-melatonin-apoptotic ADMSC; lower in lung IR-melatonin-normal ADMSC than sham controls and lung IR-melatonin-apoptotic ADMSC; lower in lung IR -melatonin-apoptotic ADMSC than sham controls (p<0.0001 in each case). Right ventricular systolic blood pressure (RVSBP) showed a reversed pattern amongst all groups (all p<0.0001). Changes in histological scoring of lung parenchymal damage and CD68+ cells showed a similar pattern compared to RVSBP in all groups (all p<0.001). Changes in inflammatory protein expressions such as VCAM-1, ICAM-1, oxidative stress, TNF-α, NF-κB, PDGF and angiotensin-II receptor, and changes in apoptotic protein expressions of cleaved caspase 3 and PARP, and mitochondrial Bax, displayed identical patterns compared to RVSBP in all groups (all p<0.001). Numbers of antioxidant (GR+, GPx+, NQO-1+) and endothelial cell biomarkers (CD31+ and vWF+) were lower in sham controls, lung IR-saline, and lung IR-melatonin than lung IR- melatonin-normal ADMSC, and lung IR-melatonin-apoptotic ADMSC, and lower in lung IR-melatonin-normal ADMSC than lung IR-melatonin-apoptotic ADMSC (p<0.001 in each case).

Conclusion:
When the animals were treated with melatonin the apoptotic ADMSC were superior to normal ADMSC for protection of lung from acute IR injury.

Key words:
acute ischemia-reperfusion lung injury, inflammation, oxidative stress, adipose-derived mesenchymal stem cells, melatonin
Abstract 9625: Late Malapposition and Endothelial Coverage of Drug-Eluting-Stents - A Prospective Optical Coherence Tomography Study
Authors: Roth Christian , Gangl Clemens , Dalos Daniel , Krenn Lisa , Scherzer Sabine , Lang Irene , Kreiner Gerhard , Delle-Karth Georg , Neunteufl Thomas , Berger Rudolf
Published: April 2024

Background:
Uncovered stent struts of drug-eluting stents (DES) are associated with late stent thrombosis. Early and late malapposition of stent struts may be the major mechanisms for uncovered struts. Data regarding coverage of malapposed struts are missing.

Aims:
This study examines malapposition of DES and the coverage of late malapposed struts in patients who underwent elective percutaneous coronary intervention (PCI).

Methods:
Fifty patients treated with 60 DES (25 Everolimus-eluting stents [EES], 18 Zotarolimus-eluting stents [ZES], 17 Biolimus-eluting stents [BES]) underwent optical coherence tomography (OCT) directly after implantation and after 12 months.

Results:
Postintervention acute stent malapposition (ASM) occurred in 30 stents (50%). Of these, 21 stents (70%) resolved completely, whereas 6 stents resolved partly and 3 persisted completely after one year. At this time-point, a total of 15 stents (25%) with late stent malappositions (LSM) were detected due to late acquired stent malapposition (LASM) in additional 10 stents (Table 1). Twelve of these 15 stents showed complete or almost complete (>80%) coverage of the malapposed struts, whereas 3 stents had no coverage of any malapposed strut (Table 2).

Conclusion:
A quarter of electively implanted DES is associated with LSM. Uncoverage of malapposed struts applies only to a minority of stents with LSM. The reason for coverage/uncoverage and the clinical impact has to be determined.
Abstract 9630: HMG-CoA Reductase Inhibitor Pitavastatin Enhances Renoprotective Effects of Angiotensin Receptor1 Blocker Olmesartan In Salt-Sensitive Hypertensive Rats
Authors: Inoue Aiko , Cheng Xian Wu , Sasaki Takeshi , Hu Lina , Jang Haiying , Xiang Li , Kuzuya Masafumi , Murohara Toyoaki , Okumura Kenji
Published: April 2024

Objective:
The present studies was undertaken to investigate the potential effect of a statin to enhance the inhibitory effect of an ARB on renal injury and the cellular mechanism of theeffect of ARB on renal remodeling and proteinuria.

Methods and Results:
Dahl salt-sensitive (DS) rats on a high-salt diet were randomly assigned to four groups (
n
= 10 for each group) that were treated with either vehicle (0.5% carboxymethyl cellulose), a low or high dosage of olmesartan (1 or 3 mg/kg/d), or pitavastatin (1 mg/kg/d) plus olmesartan (1 mg/kg/d) from 12 to 19 weeks of age. Rats fed a low-salt diet served as age-matched controls. Rats on the high-salt diet developed massive proteinuria and glomerulosclerosis, and these changes were attenuated by olmesartan in a dose-dependent manner. The amounts of mRNAs for AT1R, mineralocorticoid receptor (MR), osteopontin, monocyte chemoattractant protein-1 and collagen type I, and the activities for matrix metalloproteinase-9 and cathepsin S were significantly higher in the failing kidneys of vehicle-treated rats than in the age-matched control rats; olmesartan significantly attenuated these changes. Olmesartan attenuated both the decrease in the ratio of reduced glutathione to oxidized glutathione and the increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity apparent in the kidney cortex of vehicle-treated rats. Furthermore, olmesartan inhibited kidney cortex vascular inflammation and renal fibrosis. The addition of pitavastatin significantly enhanced these beneficial effects by AT1R antagonism via anti-inflammation and anti-proteolysis.

Conclusions:
The beneficial renal effects of AT1R antagonism are likely attributable, at least in part, to the attenuation of renal oxidative stress and renal vascular inflammation induced by the AT1R-MR signaling interaction. The combination of statin with angiotensin receptor blocker (ARB) may be a potential therapeutic strategy for renal injury with proteinuria.
Abstract 9637: Associations of Routine Repeat Stress Echocardiography With Outcomes in Stable Patients With Prior Abnormal Testing
Authors: Harb Serge C , Seicean Sinziana , Marwick Thomas H
Published: April 2024

Background:
The optimal follow-up (f-up) strategy of stable medically managed pts with previous abnormal stress imaging test results is unknown. While repeat testing is considered inappropriate early (<2 y) after the initial test, the appropriateness of later testing is indeterminate. We sought to compare the effects of a repeat testing f-up strategy to that of no repeat testing.

Methods:
We identified 606 stable pts [mean (SD) age 62.7(10.7); 52% male] with abnormal stress echocardiography (SE) results. Among these, 105 had a repeat SE >2 y after the initial test (cases) while 501 did not have repeated testing (controls). Pts were followed for 6.7 y for the occurrence of revascularization (RVS), overall and cardiac death (CD), myocardial infarction (MI) and a composite outcome of CD+MI. Association of the f-up strategy with outcomes was assessed using Cox models.

Results:
The baseline characteristics of both groups were similar. The rate of outcomes was similar in both groups except more frequent referral for RVS in cases (7.6% vs. 3.4%, p=0.04). Cox regression analyses failed to identify any significant association between the f-up strategy and any of the specified outcomes (Fig.1). The site, extent (single vs. multi-vessel) and type of the SE abnormality (ischemia or scar) were also not predictive of outcome.

Conclusion:
Routine, repeat testing during f-up is associated with higher referral rate for RVS in medically-managed pts with abnormal prior stress imaging, but no identifiable survival benefit.
Abstract 9638: Abnormal Glucose Metabolism Predicts Morbidity and Mortality in Adult Patients With Complex Congenital Heart Disease
Authors: Ohuchi Hideo , Yasuda Kenji , Ono Shin , Iwasa Toru , Negishi Jun , Noritake Kanae , Miyazaki Aya , Yamada Osamu
Published: April 2024

Background:
Adult patients with complex congenital heart disease (ACHD) have a high prevalence of abnormal glucose metabolism (AGM). However, the impact of AGM on their prognosis remains unclear.

Purpose:
This study was to clarify the prognostic value of AGM assessed by 75g oral glucose tolerance test (OGTT) in ACHD.

Method and Results:
We performed a 75g OGTT to detect AGM in 414 consecutive ACHD (27 ± 8 years), including 36 unrepaired patients (Cy), 135 Fontan patients, 243 post-biventricular patients, and 27 healthy controls (27 ± 5 years), and compared the results with the hemodynamics, neurohumoral activities, peak oxygen uptake, unscheduled hospitalization (USH), and all cause mortality. When compared with the control group, fasting blood glucose level (FBS) was lower, especially the group Cy, and postprandial hyperglycemia measured by area under the curve of glucose (BS-AUC) was higher in all ACHD groups (p < 0.0001 for all). The lower body mass index (BMI) and hypoxia independently determined the FBS, while older age, greater BMI, high plasma renin activity and central venous pressure independently determined the high BS-AUC (p < 0.05-0.01). Greater BS-AUC (per 1 g/dl, HR:1.07, 95%CI:1.01-1.13, p = 0.02) and lower FBS (per 1 mg/dl, HR:0.89, 95%CI:0.83-0.96, p = 0.002) predicted USH and mortality, respectively.

Conclusions:
Body composition and heart failure severity are closely associated with AGM in ACHD and the AGM predicts the morbidity and mortality, implying an importance of glucose metabolic management for the better long-term outcome in ACHD.
Abstract 9686: Novel GATA4 Binding Proteins, RbAp48/46 Regulate Post-Translational Modification During Hypertrophic Responses in Cardiomyocytes
Authors: Sunagawa Yoichi , Katanasaka Yasufumi , Suzuki Hidetoshi , Wada Hiromichi , Shimatsu Akira , Fujita Masatoshi , Hasegawa Koji , Morimoto Tatsuya
Published: April 2024

Introduction:
A zinc finger protein GATA4 associates with not only ERK1/2 but also an intrinsic histone acetyltransferase p300 and regulates myocardial transcriptional activities in response to hypertrophic stimuli. We recently reported that Retinoblastoma protein (Rb)-associated protein 48 and 46 (RbAp48/46) are novel components of the p300/GATA4 complex and form a repressor complex with HDACs in cardiomyocytes. However, precise functional regulation by RbAp48/46 during hypertrophic responses is still unknown.

Hypothesis:
We assessed the hypothesis that RbAp48/46 suppressed cardiac hypertrophic responses by regulating post-translational modification of GATA4 in cardiomyocytes.

Methods and Results:
Overexpression of RbAp48/46 inhibited phenylephrine (PE)-induced acetylation of GATA4, activation of atrial natriuretic factors (ANF) and endotheline-1 (ET-1) promoters, and increase in cell size in cultured cardiomyocytes. Conversely, knockdown of RbAp48/46 by shRNA augmented such responses. In the absence of HDAC1/2, RbAp48/46 failed to suppress cardiac hypertrophy. GST pull down assay revealed that RbAp48/46 interacted with a portion near the S105 phosphorylation site within N-terminal domain of GATA4. Immunoprecipitation and Western Blot demonstrated that a constituted active form of MEK1 induced S105 phosphorylation of GATA4, the dissociation between RbAp48/46 and GATA4, the increase in p300-dependant acetylation of GATA4, and p300/GATA4-dependant synergistic activations of ANF and ET-1 promoters. Such inductions did not occur in phosphorylation-mutated GATA4. Stimulation of cardiomyocytes with PE increased S105 phosphorylation of GATA4 and the dissociation of GATA4 from RbAp48/46 and HDAC1/2, and decreased recruitments of RbAp48/46 onto GATA element of the ANF promoter. These changes are suppressed by PD98059, a MEK1 inhibitor.

Conclusion:
These findings demonstrate that RbAp48 and RbAp46 form repressor complex with GATA4 as well as HDAC1/2, release p300 from GATA4, and inhibit hypertrophic responses in cardiomyocytes. The phosphorylation of GATA4 may be a trigger of the disassociation between RbAp/HDAC complex and GATA4, and of subsequent formation of p300/GATA4 complex and hypertrophic gene activation.
Abstract 9687: Network Analysis Identifies MicroRNA-22 as a Key Regulator of Vascular Calcification
Authors: Torquato Samantha , Lee Hae-Young , Maron Bradley A , Cottrill Katherine A , Chan Stephen Y , Loscalzo Joseph , Leopold Jane A
Published: April 2024

MicroRNAs (miR) have been shown to regulate expression of individual signaling molecules involved in vascular calcification. We hypothesized that downregulation of select miRs would modulate a calcification program in human coronary artery smooth muscle cells (SMC) to influence mineralization. To identify candidate miRs, we used a systems biology approach and incorporated 246 calcification-related genes into a network that revealed 3,013 interactions. A hypergeometric analysis found 9 miRNAs that regulate the network with >90% probability. Cross-referencing results with a miR microarray identified miR22 as a key regulator of the calcification network. To confirm the
in silico
analysis, SMC were transfected with anti-miR22 to decrease miR22 expression, with pre-miR22 to force miR22 expression, or with scrambled controls. Transfection with anti-miR22 increased SMC Ca
2+
levels by 126% (p<0.05), and calcification by Alizarin red staining, while transfection with pre-miR22 inhibited SMC calcification. To determine how pro-calcifying mediators decrease miR22 levels, we examined c-myc, which negatively regulates miR expression. Chromatin immunoprecipitation assay demonstrated that c-myc bound to the miR22 promoter; SMC transfection with c-myc siRNA abrograted this response and increased miR22 levels. Next, we examined expression of miR22 targets identified by the network. Transfection of SMC with anti-miR22 increased expression of cysteine-rich angiogenic protein 61 (CYR61) by 154% (p<0.01), Smad4 by 68% (p<0.04), and its downstream target Runx2 by 112% (p<0.01). Upregulation of these proteins was inhibited by forced expression of miR22. In an
ex vivo
rat aorta calcification assay, transfection of vessels with anti-miR22 increased vascular CYR61 expression and calcification, while transfection with pre-miR22 inhibited calcification. In human coronary arteries,
in situ
hybridization revealed increased levels of miR22 in vessels with limited calcification as compared to heavily calcified vessels with significant atherosclerotic disease. These findings demonstrate that miR22 modulates expression of key calcification-related intermediaries. Therapies that target this signaling pathway may limit vascular calcification.
Abstract 9688: Sleep Quality is a Significant Determinant of Executive Attention in Adults With Heart Failure
Authors: Riegel Barbara , Dinges David F
Published: April 2024

Background:
Cognitive impairment is found in 25-50% of adults with heart failure (HF). Attention is an essential component of neurocognitive functioning and very sensitive to inadequate sleep. Little is known about attention in HF relative to sleep disturbances, but in the general population women have more sleep disturbances than men. So, the purpose of this study was to identify factors associated with attention in adults with HF and determine if gender differences exist.

Methods:
Using a cross-sectional observational design, a sample of 280 adults with chronic HF was enrolled from 3 out-patient settings in the northeastern US. Patients were excluded if they had significant cognitive impairment (measured on TICS) or significant depression (PHQ-9). Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI). Attention was measured as neurobehavioral response speed (RS) on the psychomotor vigilance test (PVT)-a well-validated measure of vigilant attention deficits relative to sleep loss. General linear modeling (GLM) was performed separately by sex to identify significant determinants of RS.

Results:
Overall sleep quality was worse in women (mean 7.8±4.1, 95% CI 7.0-8.6) than men (mean 6.9±4.0, CI 6.3-7.5). Response speed was slower in women (mean 3.0 ± .73 sec, CI 2.9-3.1]) than in men (mean 3.2±.73 sec, CI 3.2-3.3]). A model of 3 variables explained 28.7% of the variance in PVT RS in women (n=100, mean age 60±12.7, 36% Black): higher PSQI daytime dysfunction from poor sleep, higher alcohol intake, and lower education levels predicted slower RS. In men (n=180, mean age 63±12.3, 33% Black), 4 variables explained 53% of the variance in PVT RS. Significant predictors of slower RS in men were worse PSQI sleep efficiency, higher PSQI daytime dysfunction from poor sleep, higher creatinine, and taking more medicines.

Conclusions:
Reduced sleep quality, as indexed by higher daytime dysfunction complaints due to poor sleep, was a significant determinant of psychomotor speed during vigilant attention performance in both women and men with HF. Sleep quality can be modified; interventions designed to improve sleep quality may improve RS and cognition in HF patients.
Abstract 97: Analysis of Emergency Medical Service-initiated CPR Effectiveness in Out-of Hospital Cardiac Arrest (OHCA) Cases Without Bystander-CPR: From all-Japan OHCA Utstein Registry
Authors: Hanada Hiroyuki , Seo Hiromi , Seino Yoshihiko , Nonogi Hiroshi , Nagao Ken , Kimura Takeshi
Published: April 2024

Backgrounds:
Bystander cardiopulmonary resuscitation (CPR) is essential for good neurological survival (GNS) in out-of-hospital cardiac arrest (OHCA). However previous reports from the All-Japan prospective, population-based OHCA Utstein registry of the Fire and Disaster Management Agency(J-OHCAUR) revealed that around 50% of OHCA did not receive bystander-initiated CPR and treated by the emergency medical service (EMS). The present study examined relationship among the time interval from the witnessed cardiac arrest to EMS-initiated CPR and shock, and GNS one month after the event.

Methods and Results:
From January 2005 through December 2011, we identified 140,363 witnessed OHCA cases from the J-OHCAUR. Among them, 74,541 cases (53.1%) did not receive bystander-CPR, and 14,911 cases had the initial rhythm of VF or VT. These EMS-initiated CPR cases were classified according to the time-interval from cardiac arrest to CPR and shock; 1,106 in the time-interval of 0 minute (shock first approach), 2.707 in 1 minute, 4.131 in 2 minutes, 2,304 in 3 minutes, 985 in 4 minutes, and 1,047 in 5 to 10 minutes. Rate of GNR (cerebral performance category scale 1 or 2) in each time-intervals were shown in the figure. Effectiveness of CPR was clearly time-dependent, and the earlier shock brought about the better GNS in any time-intervals.

Conclusion:
Even in OHCA cases without bystander-CPR, time-dependent effectiveness of EMS-initiated CPR and importance of the earlier shock were documented.
Abstract 9781: Cost-Effectiveness of Same-Day Discharge After Elective Percutaneous Coronary Intervention
Authors: Brayton Kimberly , Suen Sze-chuan , Patel Vishal G , Owens Douglas K , Goldhaber-Fiebert Jeremy D
Published: April 2024

Objective:
Same-day discharge (SDD) appears to be safe in highly selected patients undergoing PCI, however the economic impact of SDD compared to overnight observation has not been comprehensively assessed.

Methods:
We developed a decision-analytic Markov model to compare SDD to overnight observation post-PCI (Figure). Patients were followed from index PCI over remaining lifetime, including the possibility of future revascularizations. Inputs were derived from registries, RCTs, and meta-analyses. We adjusted mortality rates for having had a prior adverse procedural outcome. Costs were estimated using micro-costing (2012 USD), and outcomes were measured in QALYs, both considered from a societal perspective and discounted at 3% annually.

Results:
Base case analysis demonstrated that SDD cost $1,639 less but delivered 0.0028 fewer QALYs ($585,000 saved per QALY lost) compared to overnight observation. This result was sensitive to adverse outcome probabilities. SDD cost less and provided more QALYs when the probabilities of adverse outcomes for SDD were lower (<0.57% death, <0.60% major bleeding, or <2.32% MI) or when the probabilities of adverse outcomes for overnight observation were higher (>0.63% death, >0.90% major bleeding, or >2.89% MI). However, SDD cost more and was less effective if rates of SDD adverse events were substantially higher (>6.46% for MI) but still within the 95% confidence interval. Probabilistic sensitivity analyses revealed that SDD was frequently cost-effective even at high willingness-to-pay thresholds.

Conclusion:
SDD appears to be cost-effective if its safety profile is confirmed to be nearly identical to overnight observation. The attractiveness of SDD may depend on the ability of health systems to re-allocate resources to achieve anticipated cost savings, and to monitor and respond to adverse events out of the hospital.
Abstract 9786: Wnt11 Regulates Angiogenesis Through a Non-canonical Wnt-PKC-JNK Pathway
Authors: Wang Jingcai , Yu Bin , Gong Min , Wang Yi-Gang , Millard Ronald , Ashraf Muhammad , Xu Meifeng
Published: April 2024

Wnt11 has been implicated in stem cell proliferation and differentiation. However, its role in angiogenesis remains largely unknown. We investigated angiogenic role of Wnt11 on human vascular endothelial cells (HUVECs) and documented its related signaling pathways. HUVECs pre-labeled with PKH26 were seeded in BD Matrigel Matrix (growth factor reduced) at 1.5х10
4
/cm
2
and treated with recombinant Wnt11 proteins at 5μg/ml. Both the length and the number of capillary-like tubes (CLT) were measured after HUVECs were treated for 18 hours. Wnt11 significantly increased the number and length of CLT (Fig. A). The migration of HUVECs assessed with the BD Biocoat™ Angiogenesis System was also promoted by Wnt11 (Fig. B). Immunostaining (Fig. C) and Western blotting (Fig. D) results revealed upregulation of p-pan-PKC and p-JNK in HUVECs transfected with Wnt11 (H
Wnt11
) compared to control cells transduced with empty vector (H
GFP
). Moreover, the effect of Wnt11 on CLT formation and HUVECs migration were abrogated when the JNK inhibitor SP600125 (SP) at 5 μM and the PKC inhibitor Calphostin-C (Cal-C) at 0.1 μM were added to the culture system (Fig. E and F). Our data suggested, for the first time, that Wnt11 promotes endothelial cell migration and capillary formation, which is related to the activation of the non-canonical Wnt-PKC-JNK pathways.