bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 8322: Obesity-Related Alteration of Arterial Compliance Associated with Concentric Left Ventricular Hypertrophy Begins to Appear in Childhood
Authors: Harada Kenji , Harada Yukiko , Toyono Manatomo
Published: April 2024

Background:
Obesity is associated with worsening arterial compliance, but there is little information when arterial functional change begins to appear. The ratio of pulse pressure/stroke volume is a novel index for arterial compliance. The purpose of this study is to assess the relationship between body mass index (BMI) and this index and to investigate their relations to left ventricular (LV) geometry and function from childhood to adolescence.

Methods:
Echocardiography with tissue Doppler imaging was performed in 389 healthy subjects. Subjects were divided into 3 age groups: pre-school children group, 4 to 6 years (5±1 years, n = 125); school children group, 7 to 12 years (9±3 years, n = 176); and adolescents group, 13 to 20 years (15± 3 years, n = 88). Left ventricular (LV) end-diastolic volume and LV mass were measured and LV mass-to-volume ratio was calculated. Stroke volume (SV) was calculated using aortic diameter and pulsed Doppler velocity profile. SV was indexed for body surface area (SVI). Total arterial compliance (Ca) was estimated by the ratio of pulse pressure/SVI. Tissue Doppler-derived myocardial performance index (MPI) was calculated. Quantitative B-mode ultrasound scans were used to measure intima-media thickness (IMT) of the common carotid artery.

Results:
There was no significant relationship between BMI and Ca in the pre-school children group. However, in the school children and adolescents groups, weak but significant correlations between Ca and BMI were found (r = 0.29 and o.25, respectively, p < 0.01). Within each group, LV mass-to-volume ratio increased significantly with BMI. Ca did not correlate with LV mass-to-volume ratio in the pre-school children group, however, increased Ca correlated significantly with increased LV mass-to-volume ratio in the school and adolescents groups (r = 0.17 and 0.23, respectively, p < 0.01). There were weak but significant relationships between Ca and MPI and carotid IMT (r = 0.25 and 0.24, respectively, p < 0.01) in the adolescents group.

Conclusions:
Obesity-related changes in arterial compliance and LV geometry and function begin to appear in younger school children. Our findings suggest that primary prevention programs should be initiated in early childhood.
Abstract 8390: Contrast-Induced Nephropathy Independently Predicts Mortality After Cardiac Surgery
Authors: Garcia Santiago , Ko Byungsoo , Adabag Selcuk
Published: April 2024

Background:
Contrast induced nephropathy (CIN) is a predictor of poor outcome and long-term mortality. Coronary angiography is usually performed in close proximity to cardiac surgery. The goal of this investigation is to assess whether CIN also predicts post-surgical morbidity and mortality.

Methods:
We evaluated 949 patients undergoing cardiac surgery at the Minneapolis VA Medical Center from 2004 to 2010. The cohort was divided in 3 groups according to change in serum creatinine 48 hours post-angiography (no increase, Δ <0.5 mg/dl, and Δ ≥0.5 mg/dl). Outcomes were operative mortality and post-operative acute kidney injury (AKI) using the AKI network and RIFLE (Risk, Injury, Failure, Loss, End-stage) definitions. Multivariable logistic-regression analysis adjusting for the VA mortality risk score was performed. Estimated glomerular filtration rate (eGFR) was calculated with the Modification of Diet in Renal Disease (MDRD) method.

Results:
Mean age of the patients was 67 (±9.6) and 36% were diabetics. The mean (±SD) serum creatinine pre and post-angiogram were 1.18 (±0.39) and 1.11 (±0.41) mg/dl, with corresponding eGFR of 71.71 (±21) and 77.75 (±23) ml/m/1.73 m2. The incidence of post-operative outcomes in relation to Δ creatinine are presented in the table. In multivariable analysis, a rise in creatinine >0.5 mg after coronary angiogram was associated with a 5.6 fold increase in operative mortality after cardiac surgery (OR 5.6, 95% CI 1.3-23.7, p=0.02).

Conclusions:
The development of CIN during diagnostic angiography is an independent predictor of post-operative kidney injury and mortality after cardiac surgery. Strategy-based studies to modify this risk are warranted.
Abstract 8403: High Mobility Group Box-1 Stimulates Vascular Smooth Muscle Cells Migration via TLR4-dependent PI3K/Akt Pathway Activation
Authors: Yang Jian , Yang Jun , Ding Jia-Wang , Li Song , Dong Wu-Song
Published: April 2024

Background:
Migration of vascular smooth muscle cells (VSMCs) is a key event in neointimal formation and atherosclerosis. High mobility group box-1 (HMGB1), a highly conserved nuclear protein, can also act as an extracellular chemotactic cytokine for VSMCs. However, the role of HMGB1 receptors and details of signaling in VSMCs migration are largely unexplored. Toll-like receptor 4 (TLR4), a member of HMGB1 cell-surface receptors, is widely distributed in the vasculature. Moreover, TLR4 and its downstream PI3K/Akt pathway have been reported to regulate cell differentiation, proliferation and migration. Therefore, we determined whether TLR4 signaling and PI3K/Akt pathway activation occur in HMGB1-induced VSMCs migration.

Methods and results:
VSMCs from rat thoracic aorta were studied. We found that HMGB1 stimulated VSMCs migration in a dose-dependent manner, with the highest value (about 3.5-fold increase). In addition, incubation of VSMCs with HMGB1 (100 ng/ml) caused a rapid increase in PI3K activity and Akt phosphorylation (
P
both<0.05). Silencing of TLR4 with siRNA significantly inhibited the HMGB1-induced migration of VSMCs by 49.7±6.3%, in comparison to Control siRNA-transfected VSMCs (Figure 1,
P
<0.05). We also observed that pretreated cells with TLR4 siRNA or the PI3K inhibitor LY294002 could markedly block PI3K/Akt pathway activation and VSMCs migration mediated by HMGB1 (
P
both<0.05).

Conclusion:
These data provide the first evidence that HMGB1-induced VSMCs migration is mediated through a TLR4-dependent PI3K/Akt signaling pathway, which suggest a possible molecular mechanism for HMGB1 may contribute to neointima formation after vascular damage.
Abstract 8413: Differences in Myocyte Enhancer Factor-2 and Nuclear Factor of Activated T Cells Pathways According to Human Heart Failure Aetiology
Authors: Rivera Miguel , Cortes Raquel , Rosello Esther , Azorin Inmaculada , Salvador Antonio , Almenar Luis , Martinez-Dolz Luis , Gonzalez-Juanatey Jose , Lago Francisca , Sanchez-Lazaro Ignacio , Hove Leif , Bertomeu Vicente , Montero Anastasio , Cinca Juan , Portoles Manuel
Published: April 2024

Introduction:
Ca
2+
handling machinery modulates the activation of cardiac transcription pathways involved in heart failure (HF). The present study investigated the effect of HF aetiology on Ca
+2
handling proteins and nuclear factor of activated T cells-1 (NFAT1), myocyte enhancer factor-2 (MEF2C) and transcription factor GATA-4 (GATA4); all transcription factors in the same cardiac tissue.

Methods:
A total of 80 hearts from ischaemic (ICM, n = 43) and dilated (DCM, n = 31) patients undergoing heart transplantation and controls (n = 6) were analysed by western blotting. Subcellular distribution was analysed by fluorescence and electron microscopy.

Results:
We compared Ca
+2
handling proteins according to HF aetiology, ICM showed higher levels of calmodulin (27%, p<0.05), calcineurin (22%, p<0.05) and Ca
2+
/Calmodulin-dependent kinase II (CaMKIIδ
b
nuclear isoform 96%, p<0.01) than control group. However, these proteins in DCM did not significantly increase. Furthermore, ICM showed a significant elevation in MEF2C (23%, p<0.05), and GATA4 (51%, p<0.05); also NFAT1 (53%, p<0.01) was increased, producing the resultant translocation of this transcriptional factor into the nuclei. These results were supported by fluorescence and electron microscopy analysis. In addition, DCM only had a significant increase in GATA4 (52%, p<0.05). Correlations between NFAT1 and MEF2C in both groups (ICM r=0.36 and DCM r=0.51, p<0.05) were found; only ICM showed a correlation between GATA4 and NFAT1 (r=0.42, p<0.05).

Conclusions:
This study shows an activation of Ca
2+
handling machinery synthesis and their cardiac transcription pathways in HF, being more markedly increased in ICM. Furthermore, there is a significant association between MEF2, NFAT1 and GATA4. These proteins could be therapeutic targets to improve myocardial function.
Abstract 8434: Study of Cardiac Mechanics with a New 3D Echocardiographic Analysis Program
Authors: Panosian Jill , Zhang Jiahui , Houle Helene , Ashraf Muhammad , Sahn David J
Published: April 2024

Background:
Left ventricular (LV) twist is characterized by apical and basal rotation in opposite directions due to the helical orientation of the myocardial fibers in the normal heart.

Methods:
We developed a torsion model of pumped fresh pig hearts. A model with a variable-speed motor was used to rotate pig hearts in a water bath. We studied 3 pig hearts; the base of each heart was rotated at 0°, 10°, 15° and 20°, with the apex fixed to avoid translational motion. Stroke volumes (SV) of 40, 60 and 70 ml were used. Three-dimensional images were obtained with a Siemens Acuson SC2000 ultrasound system at maximized frame rates and measured using a new 4D strain and twist analysis program developed by Siemens.

Results:
Measured apical and basal rotations increased in a pattern similar to the actual rotations. As SVs increased, apical LV rotation also increased accordingly (p < 0.05).

Conclusions:
Increasing SV in this model correlated with increases in mid level and apical rotation, which can be explained by the helical orientation of myocardial fibers and demonstrated with Siemen's new 4D strain and twist analysis program.
Abstract 8452: Accuracy of 3D Echocardiography on Imaging Ventricular Septal Defect Size: An in vitro Validation Study
Authors: Luoh Rebecca , Gratcheva Darya , Jayaraman Aarti , Ashraf Muhammad , Sahn David J
Published: April 2024

Background:
Ventricular septal defect (VSD) is one of the most common congenital heart diseases, but the accuracy of defining VSD orifices has not been validated for 3D echo.

Methods:
We studied 4 fresh porcine hearts due to their anatomical similarity with human hearts. Each heart was connected to a calibrated pulsatile pump with different stroke volumes (SV, 30-80ml) on the left ventricular (LV) side and constant 40ml on the right ventricular (RV) side through a balloon VSD model, secured in LV and RV, that contained a tube of various size to define the VSD orifice (0.700cm, 1.00cm, 1.25cm, 1.59cm in diameter). Each heart was mounted in a water bath to facilitate ultrasound scanning and driven passively by 2 pumps at a constant rate of 50bpm. 3D images were gathered on GE Vivid 9, BT10 & BT09 and analyzed by EchoPac PC.

Results:
3D echo detected the VSD orifice, and the size can be measured accurately by the program. The measured orifice sizes increase as SVs increase except SV40. The measured value at SV60 is the closest to the actual orifice size, while the measured value is the smallest at SV40.

Conclusions:
3D echo can accurately measure the VSD orifice size, and the variation of VSD orifice with SV can be explained by mechanism of expanding and contracting of the myocardium surrounding the simulated VSD orifice by difference in stroke volumes of the two chambers.
Abstract 8506: Adaptive Servo Ventilation Improves Cardiac Function and Prognosis in Chronic Heart Failure Patients with Cheyne-stokes Respiration After Cardiac Resynchronization Therapy
Authors: Miyata Makiko , Yoshihisa Akiomi , Suzuki Satoshi , Yamada Shinya , Kamioka Masashi , Kamiyama Yoshiyuki , Yamaki Takayoshi , Sugimoto Koichi , Kunii Hiroyuki , Nakazato Kazuhiko , Suzuki Hitoshi , Saitoh Shu-ichi , Takeishi Yasuchika
Published: April 2024

Backgrounds:
Cheyne-Stokes respiration (CSR) is frequently observed in chronic heart failure (CHF) patients and is associated with adverse prognosis. Although it has been reported that cardiac resynchronization therapy (CRT) partly improves CSR, CSR often persists after CRT implantation. Therefore, we examined whether adaptive servo ventilation (ASV) improves cardiac function and prognosis of CHF patients with CSR after CRT.

Methods:
Polysomnography was performed at 12 months after CRT defibrillator (CRTD) implantation. Twenty two patients with CSR post CRTD implantation (mean age 62.0 years, AHI 36.3±19.2 /h) were enrolled in this study and randomly assigned into 2 groups: 11 patients treated with ASV (ASV group) and 11 patients without ASV (Non-ASV group). Plasma B-type natriuretic peptide (BNP) levels, estimated right ventricular systolic pressure (RVPs), and the ratio of early transmitral flow velocity to mitral annular velocity (E/E') were determined before and 6 months later in each group. Patients were followed up to register cardiac events (cardiac deaths and rehospitalization due to worsening heart failure).

Results:
In ASV group, indices for apnea-hypopnea, central apnea, and oxyhemoglobin saturation were improved on ASV. Levels of plasma BNP (Figure A), RVPs (38.1±16.8 vs. 27.4±18.4 mmHg, P<0.05) and E/E' (16.5±6.5 vs. 9.2±4.1, P<0.01) were improved with ASV treatment for 6 months, but not in Non-ASV group. Importantly, event free rate was significantly higher in ASV group than in Non-ASV group (91% vs. 45%, P<0.05) as shown in Figure B.

Conclusions:
ASV improved CSR, cardiac overload, diastolic function, and prognoisis of CHF patients with CRTD. CHF patients with CSR and post CRTD implantation would get benefits by treatment with ASV.
Abstract 8511: A Novel Type of Homozygous Familial Hypercholesterolemia:Double Heterozygous Mutations in LDL Receptor and LDL Receptor Adaptor Protein 1 Gene
Authors: Tada Hayato , Kawashiri Masa-aki , Nakanishi Chiaki , Tsubokawa Toshinari , Konno Tetsuo , Hayashi Kenshi , Uchiyama Katsuharu , Nohara Atsushi , Fujino Noboru , Ino Hidekazu , Inazu Akihiro , Kobayashi Junji , Mabuchi Hiroshi , Yamagishi Masakazu
Published: April 2024

Introduction:
Autosomal recessive hypercholesterolemia (ARH), which is due to mutations in LDL receptor adaptor protein 1 (LDLRAP1) gene is extremely rare disorder. Although it is described that this defect exhibits recessive form of inheritance, several heterozygous mutation carriers in this gene are reported to show elevated LDL-C levels. There is no data exists regarding clinical impact of double heterozygous mutations in LDLR and LDLRAP1 gene, both of which are involved in the metabolism of LDL particle.

Hypothesis:
We assessed the hypothesis that additional mutation in LDLRAP1 gene worsen clinical phenotype of heterozygous familial hypercholesterolemia (FH) that has a single mutation in LDLR gene.

Methods:
We performed genetic analyses of all coding regions in the LDLRAP1 gene for our mutation determined heterozygous FH patients with mutation in LDLR gene (n=146, mean age=56.5±16.0, mean LDL-C=265.6±57.7mg/dl).

Results:
We identified a case with double heterozygous mutations in LDLR gene (c.2431A>T) and in LDLRAP1 gene (c.606dup). Seventy-nine-year-old Japanese female exhibits severe Achilles' tendon xanthomas, the thickness of which is as much as 24mm. She underwent coronary artery bypass graft surgery due to her three vessel disease at the age of 70. Although her coronary atherosclerosis including bypass grafts did not progress substantially for a period of 9 years on more intensive medical therapy, severe aortic valve stenosis developed to cause ventricular fibrillation. And we identified 2 other relatives with the same mutations in LDLR and LDLRAP1 gene in her family. Serum LDL-C level of these 3 subjects with double mutations was significantly higher than that of the subjects with a single LDLR mutation alone (284.0±43.5 versus 265.1±57.4, p < 0.0001).

Conclusions:
These results indicate that additional mutation in LDLRAP1 gene worsens clinical phenotype of heterozygous FH that has a single mutation in LDLR gene. We suggest that ARH is not a fully “recessive” disorder, and that such cases should be diagnosed as novel type of “homozygous FH”.
Abstract 8534: Combination of Cyclosporine and Erythropoietin Improves Brain Infarct Size and Neurological Function in Rats after Ischemic Stroke
Authors: Leu, Steve , Chua Sarah , Yuen Chun-Man , Chen Yung-Long , Yip Hon-Kan
Published: April 2024

Objectives:
This study tested the superiority of combined cyclosporine (CsA)-erythropoietin (EPO) therapy compared with either one in limiting brain infarction area (BIA) and preserving neurological function in rat after ischemic stroke (IS).

Methods:
Fifty adult-male SD rats were equally divided into sham control (group 1), IS plus intra-peritoneal physiological saline (at 0.5/24/48h after IS) (group 2), IS plus CsA (20.0 mg/kg at 0.5/24h, intra-peritoneal) (group 3), IS plus EPO (5,000IU/kg at 0.5/24/48h, subcutaneous) (group 4), combined CsA and EPO treatment (group 5) after occlusion of distal left internal carotid artery.

Results:
BIA on day 21 after acute IS was highest in group 2 and lowest in group 5 (all p<0.01). The sensorimotor functional test showed highest frequency of left turning in group 2 and lowest in group 5 (all p<0.05). mRNA and protein expressions of apoptotic markers and number of apoptotic nuclei on TUNEL were highest in group 2 and lowest in group 1 and 5, whereas the anti-apoptotic markers exhibited an opposite trend (all p<0.05). The expressions of inflammatory and oxidized protein were highest in group 2 and lowest in group 1 and 5, whereas anti-inflammatory markers showed reversed changes in group 1 and 5 (all p<0.05). The number of aquaporin
-
4+ and glial fibrillary acid protein+ stained cells were highest in group 2 and lowest in groups 1 and 5 (all p<0.01).

Conclusion:
Combined treatment with CsA and EPO was superior to either one alone in protecting rat brain from ischemic damage after IS (the proposed mechanisms of potential therapeutic impact of combined therapy with CsA and EPO on acute IS have been summarized in the figure)
Abstract 8613: Load-Independency of the 2D Speckle Tracking-Derived Left Ventricular Twist and Apex-to-Base Rotation Delay in Longstanding, Non-Ischemic Dilated Cardiomyopathy
Authors: Kim Hyung-Kwan , Chang Sung-A , Shin Dong-Ho , Kim Ji-Hyun , Lee Seung-Pyo , Kim Yong-Jin , Cho Goo-Yeong , Sohn Dae-Won , Oh Byung-Hee , Park Young-Bae
Published: April 2024

Background:
Although Left ventricular(LV) twist is known to be load-dependent in healthy volunteers, this has not been examined in patients with dilated cardiomyopathy(DCMP), in whom alterations in myofiber architecture and its arrangement could perturb the intrinsic dependence of LV twist on loading conditions. This study tried to examine whether LV twist remains load-dependent in DCMP.

Methods:
34 DCMP patients with a baseline LV ejection fraction of <40% were enrolled. After baseline measurements, pneumatic compression of the lower extremities(Pcom) was employed to increase LV afterload. Subsequently, sublingual nitroglycerin(SL-NG) was administered to modify preload. Conventional echocardiographic parameters, LV end-systolic wall stress(LV-ESWS), LV twist, and apex-to-base-rotation delay were assessed under each condition.

Results:
Although LV-ESWS significantly increased under Pcom(196.9±64.9 at baseline vs. 231.8±78.9g/m
2
under Pcom,
P
<0.017) and decreased after SL-NG(231.8±78.9 under Pcom vs. 197.4±67.4g/m
2
after SL-NG,
P
<0.017), LV twist and apex-to-base rotation delay showed no significant changes with modification of LV loading condition(for LV twist, 7.78±4.63° at baseline vs. 7.19±4.34° under Pcom vs. 7.41±4.46 after SL-NG,
P
=0.65; for apex-to-base rotation delay, 16.56±13.81 at baseline vs. 17.19±14.81 under Pcom vs. 15.95±13.27 after SL-NG,
P
=0.53). Careful examination of individual patient data revealed that LV twist was load-independent when patients had a LV twist <12°. Apex-to-base rotation delay was also found to be load-independent, but only in patients with a LV ejection fraction <34%.

Conclusion:
LV twist and its component, apex-to-base rotation delay, had relatively load-insensitive properties in patients with longstanding DCMP, and can be used in future clinical trial as load-independent LV dyssynchrony indexes.
Abstract 8640: Sudden Cardiac Death and Supraventricular Tachycardia Incidence in Patients with Asymptomatic Pre-excitation - A Meta-analysis
Authors: Obeyesekere Manoj N , Leong-Sit Peter , Massel David , Krahn Andrew D , Skanes Allan C , Gula Lorne J , Yee Raymond , Klein George J
Published: April 2024

Background:
The risk of sudden cardiac death (SCD) and management of this risk in patients with asymptomatic pre-excitation is controversial. The purpose of this meta-analysis was to define the incidence of SCD and supraventricular tachycardia (SVT) in patients with asymptomatic pre-excitation.

Methods:
We performed a systematic search of prospective, retrospective, randomized or cohort, English language studies in EMBASE and Medline to February 2011. Inclusion criteria were studies of asymptomatic patients with pre-excitation who did not undergo ablation. When studies reported on symptomatic patients and/or catheter ablation of asymptomatic patients, only asymptomatic patients who did not undergo catheter ablation were included. Incidence of SCD/aborted SCD and incidence of SVT were extracted and pooled using a DerSimonian-Laird random effects model and fixed effects model to construct 95% confidence intervals (CI). Heterogeneity analyses were performed.

Results:
Twenty-one studies involving 12096 person-years (PYrs) of follow-up met our inclusion criteria. Follow-up ranged from a mean of 15 months to 21.8 years. Participants were primarily male (weighted average 67%). Mean ages in the studies ranged from 7 to 43 years. The weighted mean age was 26.5 years. SCD episodes were reported in 7 studies with 4283 PYrs of follow-up. Rates of SCD ranged from 0.7 to 8 per 1000 PYrs. No events were seen in 14 studies with a total follow-up of 7813 PYrs. Considering all patients the unadjusted rate was 1.1 SCD events per 1000 PYrs. We found moderate evidence of statistical heterogeneity (p=0.064, I
2
34.2%). Using a fixed effects model the SCD risk was estimated at 1.0 (95% CI: 0.5 to 1.7) per 1000 PYrs. Using a random effects model the risk of SCD is estimated at 1.6 (95% CI: 0.7 to 2.6) per 1000 PYrs. The development of SVT was described as an outcome in 19 studies involving 10258 PYrs. Rates in individual studies varied from 0 to 50 events per 1000 PYrs. There was no statistical evidence of heterogeneity (p<0.0001, I
2
85.3%). Using a random effects model, the overall risk of SVT was 18 (95% CI: 11 to 26) events per 1000 PYrs.

Conclusions:
The exceedingly low risk of SCD and low risk of SVT may argue for a conservative approach in managing patients with asymptomatic pre-excitation.
Abstract 8655: Caveolin-1-dependent Inhibition of Transforming Growth Factor-β Pathway Alters Inflammation Post Myocardial Infarction
Authors: Bhatnagar Harshita , Ji Lisa , Lindsey Merry L , Le Saux Claude J
Published: April 2024

Myocardial Infarction (MI) leads to inflammatory events characterized by influx of neutrophils and macrophages, altering the local cytokine milieu. TGF-β is implicated as one of the key cytokines in this process. Caveolin-1 (Cav-1), the main structural protein of caveolae, negatively modulates TGF-β signaling by regulating TGF-β receptor turnover and downstream signaling. Thus, we hypothesized that Cav-1 will modulate TGF-β anti-inflammatory responses post-MI. Two-month old wild-type (WT) C57BL/6 and the Cav-1 null mice were subjected to left anterior descending artery ligation, a subset of which were treated with TGF-β neutralizing antibodies, 24 hours post-MI. Hearts were harvested 3 days post-injury. H & E staining showed massive cell infiltration in WT mice post-MI in all groups. Neutrophil and macrophage counts paralleled this observation. Interestingly, in the Cav-1 null mice, a marked reduction in the infiltrating neutrophil and macrophage numbers was observed after anti-TGF-β treatment. Real-time PCR results further confirmed the regulatory effects of Cav-1 in the inflammatory responses. Thirty-five percent of the regulated inflammatory genes were TGF-β dependent (such as chemokine genes Ccl24 and Ccr9; cytokine genes IL-17b and Spp1 and cytokine receptor gene IL1r2). Out of them, 60% were Cav-1-dependent. For example, Ccl24, Ccr9 and IL1r2 were Cav-1 dependent whereas Spp-1 was regulated independently of Cav-1. Ccl24 expression was increased 20-fold in Cav-1 null mice post-MI compared to WT mice. This increase was further enhanced after anti-TGF-β antibody treatment. Similar results were obtained for Ccr9 and IL1r2 expressions. Spp-1 expression was upregulated by 600-fold post-MI in WT and by 400-fold in Cav-1 null mice. After anti-TGF-β antibody treatment, Spp-1 expression returned to baseline in both strains. Thus, we demonstrate for the first time that in addition to TGF-β, Cav-1 plays a significant role in the inflammatory events post-MI; and regulating TGF-β and/or Cav-1 modulates these events. It would be interesting to study if Cav-1 has a role to play in the chemotaxis of the immune cells to the site of injury and in conjunction with TGF-β, affect the secretion of cytokines and chemokines by these cells, altering post-MI events.
Abstract 8667: Carvedilol Suppresses the Structural Remodeling in the Canine Atrial Fibrillation Model via the Suppression of Periostin as a Mediator of the Extracellular Matrix Synthesis
Authors: Kishihara Jun , Niwano Shinichi , Niwano Hiroe , Aoyama Yuya , Satoh Akira , Oikawa Jun , Izumi Tohru
Published: April 2024

Background:
Periostin is a novel extracellular matrix (ECM) protein, secreted from cardiac fibroblasts, and is considered to be related with cardiac fibrosis and remodeling as one of the mediators of ECM synthesis. In our canine atrial fibrillation (AF) model, we have documented that the ECM synthesis was observed as the atrial structural remodeling and the AF inducibility was suppressed by carvedilol, a beta-blocker with the anti oxidative action. In this study, we evaluate the effect of carvedilol against the periostin synthesis and the development of structural remodeling in the canine AF model.

Methods:
AF model was produced by performing rapid atrial stimulation in 15 dogs. They were divided into 3 groups; 1) carvedilol group (n=5): 6-week pacing with carvedilol (50mg/day), 2) control group (n=5): pacing without carvedilol, and 3) non-pacing group (n=5). At the end of the protocol, atrial tissues were sampled for the evaluation of mRNA and protein expressions of periostin by the real time RT-PCR and the western blot analysis. The immuno-fluorescent staining analysis of periostin and the 8-OHdG, one of the major forms of DNA damage induced by the reactive oxygen species, were performed to evaluate the expression of periostin and oxidative stress in the atrial tissue.

Results:
The mRNA and protein expressions of periostin were up-regulated in the control in comparison with non-pacing group, and this up-regulation was suppressed by carvedilol (p<0.05). Immuno-fluorescent staining analysis exhibited abundant accumulation of periostin within the interstitial space with the fibrosis in the control, and it was suppressed by carvedilol. In the 8-OHdG staining, enhanced oxidative stress was observed in the atrial tissue in the control, but not in the carvedilol group.

Conclusion:
Periostin was remarkably up-regulated within the interstitial space in the atria with the fibrosis in our canine AF model. Because this up-regulation was suppressed by carvedilol, periostin up-regulation was speculated to be mediated by the oxidative stress in the AF model.
Abstract 8672: Neutrophil-to-Lymphocyte Ratio Predicts Prognosis in Patients with Chronic Coronary Heart Disease
Authors: Rovai Daniele , Sbrana Francesco , Cocci Franca , Papa Angela , Landi Patrizia , L'Abbate Antonio , Rossi Giuseppe
Published: April 2024

Purpose:
A relationship between blood cell count and survival has been observed both in healthy individuals and in patients with stable angina, unstable angina, myocardial infarction or heart failure. We tested the hypothesis that a complete blood count with subfraction concentrations would provide prognostic information in patients with chronic coronary heart disease (CHD), and that this information is additive to a standard diagnostic work-up.

Methods:
We prospectively examined 2370 consecutive patients with chronic CHD, defined by a > 50% stenosis at coronary angiography and/or history of myocardial infarction (MI). We examined the association between complete blood count, clinical variables and future cardiac events (cardiac death and non-fatal MI).

Results:
During follow-up (median 46 months), 147 patients (6.2%) died of cardiac causes and 81 (3.4%) experienced a non-fatal MI. Using univariate analysis, reduced hematocrit (< 36% if male and < 40% if female) and a neutrophil-to-lymphocyte (N/L) ratio > 2.42, but not white blood cell count and platelet count, were significantly associated with a reduced cardiac event-free survival (P < 0.001 and P < 0.0001, respectively). The impact of anemia and high N/L ratio on survival persisted after adjustment for age, diabetes mellitus, left ventricular ejection fraction and angiographic extent of coronary atherosclerosis. The negative prognostic impact of a high N/L ratio persisted even after adjustment for both clinical variables and other routine laboratory variables (risk ratio: 1.57, 95% confidence interval: 1.19 to 2.08, p = 0.0014).

Conclusion:
An elevated N/L ratio is a significant predictor of adverse prognosis in patients with chronic CHD.
Abstract 8689: Platelet CD40 Receptor Expression Accelerates Platelet Induced Atherogenesis
Authors: Lievens Dirk , Seijkens Tom , Thevissen Larissa , Beckers Linda , Wijnands Erwin , Soehnlein Oliver , Gerdes Norbert , Weber Christian , Lutgens Esther
Published: April 2024

Beyond an eminent role in hemostasis and thrombosis, platelets are important mediators of inflammation and protagonists of atherogenesis. Here we investigated the inflammatory propensity of platelet-specific expression of the CD40 receptor, an integral membrane protein of the tumor necrosis factor receptor (TNF-R) family. Besides its presence on immune and other cell types the CD40 receptor is constitutively expressed on platelets where its function remains unknown. Platelets were isolated from Apoe−/− or Cd40−/−Apoe−/− mice, activated with thrombin, and injected (3x107 platelets, i.v.), into 17-week-old Apoe−/− mice every 5 days for 12 weeks. Compared to infusion of activated Apoe−/− (wild type) platelets, injection of activated Cd40−/−Apoe−/− platelets caused a 73% decrease in plaque size (Apoe−/− platelets 18.3x104 + 2.7x104 μm2 vs Cd40−/−Apoe−/− platelets 6.7 x104 + 2.1 x104 μm2, Vehicle 9.8 x104 + 2.8 x104 μm2, p<0.05) in the aortic arch. Absence of CD40 on platelets reduced the absolute number of plaque macrophages (Mac-3) by 39% but did not affect the content of CD45+ cells and CD3+ T lymphocytes. Flow cytometric analysis revealed an elevated number of circulating Ly6G+ neutrophils (+32%) upon injection of activated platelets. However, this increase was absent when CD40-deficient platelets, were injected highlighting the inflammatory potential of platelets and a central role for CD40 in this process. In addition, we detected a 20% decrease in the formation of platelet-leukocyte aggregates in vitro while intravital microscopy in carotid arteries showed a 2-fold decrease of platelet adhesion to the vessel wall of mice, injected with activated Cd40-/- platelets, In sum, this study reveals that platelet CD40 promotes atherosclerosis by interaction with both neutrophils and endothelial cells, thereby amplifying leukocyte recruitment to sites of vascular injury.
Abstract 8693: Knockout of p47
phox
Attenuates Angiotensin II-induced Endothelial Dysfunction and Vessel Damage in Vivo
Authors: Du Junjie , Li Jian-Mei
Published: April 2024

Increased bioavailability and activity of angiotensin II (AngII) have been found to be associated with vascular oxidative stress derived from a Nox2 enzyme. The Nox2 has several regulatory subunits i.e. p40
phox
, p47
phox
, p67
phox
and rac1. However, it is unclear about the role of p47
phox
(a key regulatory subunit of Nox2 activation) in mediating AngII-induced vessel dysfunction. In this study, we examined the effect of p47
phox
knockout (KO) on AngII-induced hypertension and aortic dissection using littermates of C57BL/6 wild-type (WT) and p47
phox
KO mice (n=7) at the age of 10~12 months. In WT mice, AngII infusion (1.15mg/kg/day delivered by osmotic mini-pump for 14 days) increased significantly the systolic blood pressure (SBP) from 127 + 13 to 172 + 11 mmHg, and this was accompanied with significant indication of cardiac hypertrophy (heart/body weight ratio increased ~17.9 + 0.1%) as compared to vehicle infused controls (P < 0.05), and 3 out of 7 AngII-infused WT mice developed aortic dissection. However, in p47
phox
KO mice, AngII infusion caused a mild increase in SBP (from 119 + 9 to 149 + 10 mmHg, P<0.05) without significant increase in heart/body weight ratio, and there was no aortic dissection in AngII-infused KO mice. Aorta organ bath showed that AngII-infusion reduced significantly the endothelium-dependent vessel relaxation to acetylcholine in WT mice (Emax from 82.10 + 8.73% to 54.37 + 6.91%, P < 0.05), which can be returned to the control level by adding a superoxide scavenger, tiron. However, AngII had no significant effect on endothelium-dependent vessel relaxation to acetylcholine in the p47
phox
KO mice (Emax from 73.08 + 1.15% to 65.73 + 5.35%). In conclusion, p47
phox
plays a critical role in mediating AngII-induced endothelial dysfunction, hypertension and aortic dissection. Knockout or inhibiting p47
phox
may protect vessels from these AngII-induced vascular disorders.
Abstract 8713: Relative Impact of Surgeon and Center Volume on Outcome Following the Norwood Operation
Authors: Hornik Christoph P , He Xia , Li Jennifer , Jacobs Jeffrey P , Jaquiss Robert D , Jacobs Marshall L , O'Brien Sean M , Welke Karl F , Peterson Eric D , Pasquali Sara K
Published: April 2024

Background:
Prior studies have shown that center volume is associated with outcome after the Norwood operation. In adults undergoing cardiac surgery, this volume-outcome relationship has been found to be largely related to surgeon volume. It is unknown whether this is also true for the Norwood operation. We evaluated the relative impact of surgeon and center volume on mortality in a large Norwood cohort.

Methods:
Infants in the Society of Thoracic Surgeons Congenital Heart Surgery Database undergoing the Norwood operation (2000-2009) were included. Nested regression models were used to evaluate the relationship between in-hospital mortality and annual center and surgeon volume adjusting for patient demographic/anatomic factors.

Results:
2555 infants underwent surgery at 53 centers [64% (0-10 cases/yr), 25% (11-20 cases/yr), and 11% (>20 cases/yr)] by 111 surgeons [50% (0-6 cases/year), 39% (7-12 cases/yr), and 11% (>12 cases/yr)]. Overall unadjusted mortality was 22%. In adjusted analysis (Figure), lower center volume was associated with higher mortality (p=0.03 when analyzed as continuous variable; OR for centers with 0-10 vs. >20 cases/yr = 1.6, 95% CI 1.1-2.3, p=0.03). Surgeon volume was not significantly associated with mortality when analyzed as a continuous or categorical variable. When analyzed together, surgeon volume accounted for only a small proportion (11%) of the effect of center volume. At high volume centers, low and high volume surgeons had similar adjusted mortality rates [19% (95%CI 12-27%) vs. 19% (95%CI 16-22%), p=0.7] which were lower than mortality at low volume centers.

Conclusions:
This analysis suggests outcome following the Norwood operation is influenced more by center rather than surgeon volume. Further investigation is necessary to identify characteristics of high volume centers which may influence outcome, such as processes of care, training and availability of personnel, or senior surgeon mentoring.
Abstract 8727: Baseline Functional Status and the Benefit of Cardiac Resynchronization Therapy in Patients with Mildly Symptomatic Heart failure Enrolled in MADIT-CRT
Authors: Brenyo Andrew , Barsheshet Alon , Rao Mohan , Zareba Wojciech , Moss Arthur , Goldenberg Ilan
Published: April 2024

Background:
The MADIT-CRT trial showed that cardiac resynchronization therapy with a defibrillator (CRT-D) is associated with a significant reduction in the risk of heart failure (HF) or death in mildly symptomatic patients with left ventricular dysfunction. The aim of the present study was to relate the clinical benefit of CRT-D therapy to baseline functional status, as determined by the 6 minute walk test (6MWT), and to assess the effect of the device on functional status at 1-year in the MADIT-CRT population.

Methods:
Multivariate Cox proportional hazards regression modeling was used to assess the effect of CRT-D vs. defibrillator-only therapy on the risk of HF or death and the separate occurrence of all-cause mortality by baseline functional status (dichotomized at the median value of the baseline 6MWT [350 m]) among 1765 patients enrolled in MADIT-CRT.

Results:
A lower functional status (6MWT <350m) was associated with a 73% (p < 0.001) increase in the risk of HF or death and a 2.4-fold increase in all-cause mortality among patients treated with defibrillator-only therapy. After multivariate adjustment for relevant covariates CRT-D therapy was associated with a significant 48% (p=0.01) reduction in the risk of all-cause mortality among study patients with a lower functional status who had LBBB at enrollment (Fig.1A), whereas treatment with the device was not associated with a significant survival benefit among study patients with a higher function status (6MWT ≥350m) with LBBB (Fig. 1B). At 1-year of follow-up, improvement in 6MWT was observed in a similar proportion of CRT-D patients (50.2%) and defibrillator-only patients (50.7%) p = 0.84.

Conclusions:
A low baseline functional status is a powerful predictor of HF or death among mildly symptomatic HF patients and identifies patients in this population who derive a significant survival benefit from cardiac resynchronization therapy.
Abstract 8787: Comparative Study of Angiotensin Receptor Blocker with or Without PPAR-γ Properties on Endothelial Function and Aortic Stiffness in Hypertensive Patients with Chronic Kidney Disease and the Metabolic Syndrome
Authors: Watanabe Hideki , Nakagawa Kunio , Kakihana Masaaki
Published: April 2024

Background:
Chronic kidney disease (CKD) and the metabolic syndrome(MetS) are recognized as risk factors for cardiovascular disease. Recently it has been reported that telmisartan and irbesartan, angiotensin receptor blockers (ARB), has an action of PPAR - γ agonist. We compared the effects on endothelial function and aortic stiffness in hypertensive patients with CKD and MetS between angiotensin receptor blockers with PPAR-γ properties (telmisartan and irbesartan) and without PPAR-γ properties (losartan and valsartan).

Methods:
Ninety six untreated hypertensive patients with CKD (stage 3) and the metabolic syndrome were randomized to receive telmisartan (Telmisartan group, n=26, 20-40 mg/day), irbesartan (Irbesartan group, n=23 100-200 mg/day), losartan (Losartan group, n=22, 50-100 mg/day) or valsartan (Valsartan group, n=25, 80-160 mg/day). Flow-mediated dilatation (FMD) and nitroglycerin-induced dilatation (NID) of brachial artery were measured by using ultrasound system. Pulse wave velocity (PWV) was measured by using oscilometric technique (form PWV/ABI
®
, Colin Co, Japan). We also assessed insulin resistance by HOMA-IR. Measurements were performed at baseline, and then at 6 and 12 months after the treatments.

Results:
At baseline, there were no differences in FMD, PWV, and HOMA-IR between the four groups. After 12 months, there was no difference in blood pressure between four groups. FMD were significantly increased, and PWV was significantly decreased in four groups as compared with the baseline. However, these improvements were much better in the telmisartan group and the irbesartan group as compared with the losartan group and the valsartan group, and HOMA-IR was improved only in the telmisartan group and the irbesartan group.

Conclusion:
Telmisartan and irbesartan with PPAR-γ properties improve not only insulin resistance, but also endothelial function and aortic stiffness in hypertensive patients with CKD and MetS.
Abstract 8793: Impact of Cardiorespiratory Fitness on Characteristics of Coronary Plaque: Assessment Using Integrated Backscatter Intravascular Ultrasound and Optical Coherence Tomography
Authors: Yoshikawa Daiji , Ishii Hideki , Kurebayashi Nobutake , Sato Bummei , Hayakawa Seiichi , Tanaka Miho , Kumagai Soichiro , Hayashi Mutsuharu , Murohara Toyoaki
Published: April 2024

Background:
Cardiorespiratory fitness (CRF) is a predicter for the future cardiovascular disease. Rupture of vulnerable plaque that often has a large lipid core with a thin fibrous cap results in acute coronary syndrome including sudden cardiac death. We hypothesized that preserved CRF is associated with low lipid composition and thick fibrous cap thickness of coronary plaques.

Methods:
Both integrated backscatter intravascular ultrasound (IB-IVUS) and optical coherence tomography (OCT) were performed for 77 non-culprit coronary plaques in 77 consecutive angina pectoris patients undergoing percutaneous coronary intervention (PCI). As an indicator of CRF of patient, percentage of achieved of predicted peak oxygen consumption (%PPeak Vo
2
) calculated based on peak Vo
2
which were directly mesured using a cardiopulmonary exercise testing post PCI was adapted.

Results:
Patients were classified into two groups [those with preserved CRF (%PPeak Vo
2
>82%) (group I) or others (group II)]. Coronary plaques in patients of group I had significantly smaller lipid volume, greater fibrous volume, and thicker fibrous cap thickness than those in group II (32±14% vs. 45±13%, p<0.001; 57±11% vs. 49±11%, p<0.001; and 177.7±20.9μ m vs. 143.7±36.9μ m, p<0.001). After multivariate linear regression analysis, %PPeak Vo
2
had a significantly negative correlation with lipid volume and a positive correlation with fibrous volume and fibrous cap thickness (β=-0.418, p=0.001; β=0.361, p=0.006; and β=0.339, p=0.008).

Conclusions:
High %PPeak Vo
2
was associated with low lipid volume, high fibrous volume and thick fibrous cap thickness in coronary plaques. Those results may explain a decreased risk of cardiovascular events in patients with preserved CRF.
Abstract 8798: Ethnic Differences in the Phenotypic Expression of Hypertrophic Cardiomyopathy
Authors: Sheikh Nabeel , Papadakis Michael , Chandra Navin , Ghani Saqib , Bastiaenen Rachael , Zaidi Abbas , Muggenthaler Martina , Raju Hari , Behr Elijah , Sharma Sanjay
Published: April 2024

Purpose:
Hypertrophic Cardiomyopathy (HCM) is a heterogeneous condition with variable phenotypic expression. Current studies are based on predominantly Caucasian cohorts (white patients; WP), and the phenotypic manifestations of HCM in individuals of African/Afro-Caribbean origin (black patients; BP) are not fully realized. Data in athletes and hypertensive patients indicate that black ethnicity is associated with a greater prevalence of repolarisation abnormalities on the ECG as well as a greater magnitude of left ventricular hypertrophy (LVH), highlighting the importance of defining the HCM phenotype in this ethnic group.

Methods:
Between 2001 and 2010, 155 consecutive patients with HCM (52 BP, 103 WP) were assessed in 3 specialist cardiomyopathy clinics. All underwent comprehensive evaluation including 12 lead ECG and echocardiography.

Results:
Black patients exhibited significantly different echocardiographic patterns of LVH, with more concentric (44.2% vs. 30.1%) and apical (28.8% vs. 11.7%) hypertrophy compared to WP, who exhibited more asymmetric septal hypertrophy (57.3% vs. 25.0%) (p=0.004). Black patients exhibited a similar magnitude of LVH compared to WP (maximum left ventricular wall thickness 17.3±4.9 mm vs. 18.8±4.1 mm, p=0.069). Relating to ECG repolarisation abnormalities, BP exhibited significantly more T wave inversions in the lateral leads (76.9% vs. 60.2%, p=0.038) and deep (≥ 0.2 mV) T wave inversions (69.2% vs. 51.5%, p=0.035). Black patients also displayed more ST segment depression (50.0% vs. 35.0%, p=0.071), although this was not statistically significant. In contrast, WP had significantly more pathological Q waves (23.3% vs. 9.6%, p=0.039).

Conclusions:
Ethnicity appears to exert a significant effect on the ECG and echocardiographic patterns in patients with HCM. A significant proportion of black patients exhibit concentric LVH, highlighting the diagnostic challenges in distinguishing HCM from hypertensive heart disease and physiological adaptation to exercise in black individuals. The greater prevalence of deep T wave inversions and T wave inversions in the lateral leads underscores the importance of further evaluation of black individuals with such ECG repolarisation abnormalities.
Abstract 88: Simple Stepstool Adjuncts Improve Depth and Duration of AHA Guideline-Compliant Chest Compressions
Authors: Viteri Shirley D , McBride Michael G , Sutton Robert M , Nadel Frances M , Niles Dana , Nishisaki Akira , Zhang Xuemei , Paridon Stephen M , Berg Robert A , Nadkarni Vinay M
Published: April 2024

Introduction
AHA guideline-compliant chest compressions (CCs) during cardiac arrest improve survival. Few studies assess optimal use of stepstools (adjuncts) to improve compliance of these guidelines.

Hypothesis
Stepstool use will increase the depth and duration of AHA guideline-compliant CC delivery in a pediatric cardiac arrest manikin model.

Methods
IRB-approved prospective, randomized trial conducted on healthcare providers who routinely deliver CCs at work. Volunteers performed 2 sessions of continuous CCs on a pediatric manikin, in random order on separate days. CCs were performed with vs. without use of a 13cm stepstool on a standard-height hospital stretcher (70cm) until maximal fatigue or 10 min. Quality parameters (CC depth, rate, % CCs with residual leaning force >2.5kg) were recorded using a CPR-sensing automated feedback-enabled defibrillator. Data were analyzed in 30-second epochs. “AHA guideline-compliant” CCs were defined by achieving all 3 criteria: average depth ≥38mm, rate 90-120 CC/min, and residual leaning force in <20% of CCs. “Time to failure” was defined as the first epoch where AHA guideline-compliant CC criteria were not met. Analysis included descriptive summaries, Student's t-test, Poisson regression, and Cox regression to produce a failure-time analysis.

Results
All 21 providers completed both sessions: 62.5% male; median age 34 years, range 28-60; median height 173cm, range 163-190cm. With stepstool adjunct, subjects attained goal mean CC depth ≥38mm in over twice as many epochs (RR 2.26; CI: 1.24, 4.12; p=0.008), without significant difference in mean rate or % CCs with leaning force >2.5kg. Median time to failure (duration) to perform AHA guideline-compliant CCs was significantly longer with stepstools (3.5min) than without stepstools (6.0min) (HR 1.53; CI: 1.06, 2.21; p=0.023).

Conclusions
Stepstool adjunct increased the frequency of attaining goal depth, and time to failure (duration) of AHA guideline-compliant CCs, without increasing residual leaning force in this pediatric cardiac arrest manikin model. With stepstools, AHA guideline-compliant CCs were delivered for close to twice as long. Assessment in the clinical setting is warranted to evaluate the utility of these findings.