bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9663: Sirt7 Contributes to Proper Wound Healing After Murine Model of Myocardial Infarction by Modulating the Fibroblast Differentiation
Authors: Araki Satoshi , Izumiya Yasuhiro , Senokuchi Takafumi , Rokutanda Taku , Hanatani Shinsuke , Bober Eva , Braun Thomas , Yamagata Kazuya , Ogawa Hisao
Published: April 2024

Introduction:
Sirt7 is the only mammalian sirtuin which is localized predominantly in the nucleoli. To date, little is known about the role of Sirt7 in wound healing in the setting of acute cardiac insult.

Hypothesis:
Sirt7 contributes to proper wound healing processes after myocardial infarction (MI) by modulating cardiac fibroblast function.

Methods:
MI was created in 10-week-old male homozygous Sirt7 deficient (Sirt7-/-) and wild-type (WT) mice by the permanent ligation of the left anterior descending coronary artery. Cardiac function and structure were assessed by micromanometer catheter, echocardiography, histology and gene expression analyses. Sirt7 knockdown experiments were performed with rat neonatal cardiac fibroblast and human skin fibroblast.

Results:
Sirt7 transcript expression was increased by 2.5-fold in the border zone (BZ) of myocardial tissues at 3 days after MI in WT mice. Body weight, heart rate, systolic blood pressure, echocardiographic and hemodynamic parameters did not differ between Sirt7-/- and WT mice at 3 days after MI. However, the number of mice that died of cardiac rupture within 1 weeks after MI was significantly higher in Sirt7-/- mice (63%, 12 of 19 mice) than in WT mice (21%, 5 of 24 mice) (P<0.01). Histological analysis revealed that interstitial fibrosis and α-SMA positive fibroblast in the BZ of myocardium was significantly decreased in Sirt7-/- mice, despite the same infarct size between both groups. These changes were accompanied by the reduction in collagen I and α-SMA gene expression. In vitro, Sirt7 transcripts expression was readily detectable in total RNA isolated from rat neonatal cardiac fibroblast and human skin fibroblast. Knockdown of endogenous Sirt7 expression by small interfering RNA attenuated TGF-β1-induced PAI-1 and α-SMA expression. Conversely, adenovirus-mediated overexpression of Sirt7 augmented TGF-β1-induced α-SMA gene expression. TGF-β1-induced ERK phosphorylation was blocked by Sirt7 knockdown. However, phosphorylation and translocation of smad2 was not changed by Sirt7 knockdown.

Conclusions:
Sirt7 modulates cardiac fibroblast differentiation which is dependent on ERK signaling. Sirt7 contributes to proper wound healing process after experimental myocardial infarction.
Abstract 9665: PKA / CREB Pathway Initiates Endothelial And Hematopoietic Cell Differentiation Via Etv2 Induction
Authors: Yamamizu Kohei , Matsunaga Taichi , Katayama Shiori , Yamashita Jun K.
Published: April 2024

Ets-family protein Etv2 (also called ER71 or Etsrp) is a key factor for vascular and blood development from mesodermal cells. However, regulatory mechanisms and a triggering signal for Etv2 expression have been largely unknown. We previously established an ES cell differentiation system that reproduces early vascular development using vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2)-positive cells as common vascular progenitors. Recently, we revealed that cAMP/protein kinase A (PKA) signaling enhanced differentiation of vascular progenitors into endothelial cells (ECs) and hematopoietic cells (HPCs) using this system. Here we show that PKA activation induces Etv2 expression, which can trigger EC/HPC differentiation. We found that Etv2 was markedly upregulated by PKA activation preceding EC and HPC differentiation. Inhibition of Etv2 using siRNA completely abolished PKA-elicited EC and HPC differentiation from ES cells. We identified two cAMP response element (CRE) sequences in Etv2 promoter region, and confirmed that CRE-binding protein (CREB) directly binds to the CRE sites. Furthermore, PKA activated Etv2 promoter activity in luciferase assay, which was disappeared in CRE-mutant Etv2 promoters. Expression of dominant negative form of CREB completely inhibited PKA-elicited Etv2 expression and induction of EC/HPCs from ES cells. PKA/CREB pathway is, thus, a critical regulator for the initiation of EC/HPC differentiation through Etv2 transcription. This early stage molecular linkage between a triggering signal and transcriptional cascades for differentiation would provide novel insights in vascular and blood development and novel molecular targets for vascular and blood regeneration medicine.
Abstract 9676: Additive Prognostic Value of Diastolic Dysfunction and Coronary Flow Reserve in Non-Ischemic Dilated Cardiomyopathy
Authors: Ciampi Quirino , Rigo Fausto , Pratali Lorenza , Gherardi Sonia , Cortigiani Lauro , Villari Bruno , Picano Eugenio , Sicari Rosa
Published: April 2024

Background.
Coronary flow reserve (CFR) on left anterior descending (LAD) can be reduced in non-ischemic dilated cardiomyopathy (DCM). Aim of the study was to assess the additive prognostic value of CFR in LAD and resting severe diastolic dysfunction to identify responders to CRT.

Methods.
One hundred twenty-nine DCM patients (pts, 87 men, 62±12 years, ejection fraction: 33±7%) underwent dipyridamole (0.84 mg/kg in 6′) stress echo. CFR was defined as the ratio between maximal vasodilation and rest peak diastolic flow velocity in LAD, and diastolic dysfunction as the presence of resting irreversible restrictive transmitral pattern.

Results.
We divided DCM pts in 4 groups, according to normal (>2, 56 pts) or abnormal (≤2, 73 pts) CFR on LAD and absence (88 pts) or presence (41 pts) of restrictive transmitral pattern. In pts with abnormal CFR on LAD, the additional presence of restrictive patterns was associated to lower ejection fraction at rest (26±5% vs 31±7% p=.007) and at peak stress (30±5% vs 36±8% p=.03) and larger end-systolic volume at rest (149±55 ml vs 185±48, p=.030). During median follow-up of 30 months, 19 deaths, and 33 cardiac adverse events. Abnormal CFR on LAD and diastolic dysfunction were associated with poorer event-free survival (Log Rank: 33.1, p<0.0001, Figure), with additive negative prognostic value in pts with CFR on LAD <2 and the presence of restrictive pattern.

Conclusions.
In DCM patients with reduced CFR left anterior descending territory during vasodilator stress, the associate presence of restrictive transmitral pattern is an additive independent prognostic marker of bad prognosis.
Abstract 9679: Fast/Glycolytic Skeletal Muscle Growth Attenuates Cardiac Dysfunction and Remodeling After Experimental Myocardial Infarction
Authors: Hanatani Shinsuke , Izumiya Yasuhiro , Araki Satoshi , Rokutanda Taku , Walsh Kenneth , Ogawa Hisao
Published: April 2024

Introduction:
It is appreciated that aerobic endurance exercise can attenuate unfavorable myocardial remodeling post myocardial infarction (MI). In contrast, little is known about the effect of resistance exercise on these processes, partly because animal models that can assess the relationship between glycolytic muscle fiber growth and cardiac remodeling have been lacking.

Hypothesis:
Fast/glycolytic skeletal muscle growth attenuates cardiac dysfunction and remodeling after MI.

Methods:
We utilized skeletal muscle-specific, conditional Akt1 transgenic (TG) mice, that can induce the growth of functional fast/glycolytic skeletal muscle by switching Akt1 signaling on in muscle fibers. Male non-induced TG mice and their non-transgenic littermates (control) were subjected to left anterior descending coronary artery ligation. Two days after surgery, mice were provided doxycycline in their drinking water to activate Akt1 transgene expression in a skeletal muscle-specific manner. Cardiac function and remodeling were assessed by micromanometer catheter, echocardiography, histology and gene expression analyses at 2 and 4 weeks after surgery.

Results:
Activation of Akt1 signaling in myofibers led to a modest increase in skeletal muscle mass. Skeletal muscle-specific activation of Akt1 led to diminished left ventricular dilation and reduced contractile dysfunction compared with control mice at 4 weeks after MI. The increase in heart weight/BW ratio and lung wet weight/BW ratio was significantly diminished in Akt1 TG mice compared to control mice, consistent with an improvement in heart function. Improved cardiac function in Akt1 TG mice was coupled to diminished myocyte hypertrophy, decreased interstitial fibrosis in the infarct border zone, and increased capillary density in the remote zone. Comprehensive protein array analysis showed that panels of angiogenic factors were increased in skeletal muscle in TG mice. An ELISA analysis demonstrated that serum VEGF levels were upregulated in Akt1 TG mice compared with control mice.

Conclusions:
Akt1-mediated skeletal muscle growth attenuates cardiac remodeling after MI, and this is associated with increased capillary density in the heart and a reduction in cardiac fibrosis.
Abstract 9681: Pre-Procedural Serum Albumin and C-reactive Protein Levels Predict Clinical Outcome After Endovascular Therapy in Hemodialysis Patients with Peripheral Artery Disease
Authors: Kawamura Yoshihiro , Ishii Hideki , Yoneda Kouhei , Kawashima Kazuhiro , Kamoi Daisuke , Sakakibara Takashi , Furuhashi Kyuuichi , Aoyama Toru , Kumada Yoshitaka , Takahashi Hiroshi , Tanaka Miho , Murohara Toyoaki
Published: April 2024

Background:
Although endovascular therapy (EVT) has become widely performed for peripheral artery disease (PAD), adverse events such as high restenosis rate or premature death after EVT remain major clinical problems in patients on hemodialysis (HD). On the other hand, malnutrition and chronic inflammation status are frequently observed, and linked to poor cardiovascular outcome in such population. We evaluated the possible prognostic values of serum albumin and C-reactive protein (CRP) levels on clinical outcomes after EVT in patients on HD.

Methods:
A total of 450 HD patients successfully undergoing EVT for PAD were enrolled and were followed-up for up to 8 years. Serum albumin and CRP levels were measured prior to EVT. They were divided into tertiles according to serum albumin and CRP levels; the lowest tertile (T1), the middle tertile (T2) and the highest tertile (T3), respectively. We analyzed the incidence of major adverse cardiovascular events (MACE) as a composite endpoint including target lesion revascularization (TLR), amputation and all-cause death.

Results:
During follow-up period (mean 36±31months), 206 MACE (46%) including 67 TLRs, 45 amputations and 94 deaths occurred. Event-free survival rate from MACE for 8 years was 23.1%, 25.9%, and 50.0% in T1, T2 and T3 of albumin (p<0.0001), and 41.2%, 36.3% and 18.9% in T1, T2 and T3 of CRP (p=0.0004), respectively. After adjustment, lower albumin (HR 2.00, 95%CI 1.29-3.10, p=0.0071 for T1 vs. T3) and elevated CRP (HR 1.93, 95%CI 1.29-2.90, p=0.0061 for T3 vs. T1) were independent predictors for MACE, respectively. Furthermore, in the combined setting of albumin and CRP, the risk of MACE was 5.22-fold (95%CI 2.34-11.64, p=0.0011) higher in the T1 of albumin with T3 of CRP compared to the T3 of albumin with T1 of CRP even after adjustment (Figure).

Conclusions:
Lower albumin and elevated CRP levels could strongly predict MACE after EVT in patients on HD. However, the combination of these variables is more markedly related to increased MACE than either variable alone.
Abstract 9689: Nitinol Stents Implantation Improves Clinical Outcome After Endovascular Therapy in Hemodialysis Patients with Superficial Femoral Artery Lesions
Authors: Kawamura Yoshihiro , Ishii Hideki , Yoneda Kouhei , Kawashima Kazuhiro , Kamoi Daisuke , Sakakibara Takashi , Furuhashi Kyuuichi , Aoyama Toru , Kumada Yoshitaka , Takahashi Hiroshi , Tanaka Miho , Murohara Toyoaki
Published: April 2024

Background:
Although endovascular therapy (EVT) has become widely performed for peripheral artery disease, high restenosis rate remains major problem after EVT to lesion of superficial femoral artery (SFA). Recently, it has been reported that nitinol stent implantation reduced restenosis in SFA after EVT in general population, however, the clinical outcome is little known in hemodialysis (HD) patients. The aim of this study was to investigate whether nitinol stent implantation improves clinical outcome after EVT to SFA lesions in HD patients.

Methods:
A total of 173 consecutive patients underwent nitinol stents implantation (NS group) were compared with 75 patients received stainless steel stents implantation in the preceding 5 years (SS group). We analyzed incidence of major adverse cardiovascular events (MACE) including target lesion revascurlarization (TLR), major amputation and death. To minimize the differences in both groups, a propensity-matched analysis using logistic model including male, age, traditional risk factors, critical limb ischemia (CLI) and TASC C+D lesions was performed. Each patients implanted with stainless steel stents were matched with up to two patients implanted with nitinol stents with two-digit propensity score (AUC = 0.63 using ROC analysis).

Results:
Baseline characteristics were comparable in both groups. On Kaplan-Meier analysis, 5-year freedom rate from MACE was higher in NS group than in SS group (51.8% vs. 24.4%, p<0.0001). After adjustment, nitinol stent implantation was an independent predictor of reducing MACE [HR 0.41, 95% CI 0.25-0.65, p=0.0002]. After the propensity score matching, 106 patients in NS group and 66 patients in SS group were matched. Still, freedom from MACE was higher in NS group than in SS group (47.7% vs. 24.6%, p<0.0001). Even after adjustment for other variables, implantation of nitinol stent predicted reduction of MACE (HR 0.47, 95% CI 0.28-0.79, p=0.0045). Nitinol stent implantation was also a predictor for not only preventing TLR (HR 0.35, 95%CI 0.18-0.68, p=0.0020) but also limb salvage (HR 0.26, 95%CI 0.07-0.96, p=0.043).

Conclusion:
Nitinol stent implantation improved clinical outcome after EVT compared to stainless steel stents in HD patients with SFA lesions.
Abstract 9713: Cigarette Smoking: Relationship with Inflammation, Arterial Stiffness, and Subclinical Atherosclerosis. The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Mcevoy John W , Blaha Michael J , Lima Joao A , Bluemke David A , Hundley Gregory , Min James K , Shaw Leslee J , Lloyd-Jones Donald M , Barr Graham , Budoff Matthew J , Blumenthal Roger S , Nasir Khurram
Published: April 2024

Background:
Smoking is a major reversible cardiovascular risk factor. Population studies, incorporating measures of inflammation and subclinical atherosclerosis, may provide a means to study the effects of smoking further.

Methods:
MESA is a population-based study of 6815 adults, free of baseline cardiovascular disease. We stratified participants based on smoking status into 3 groups: Never (NS), Former (FS), and Current (CS). FS and CS were further stratified into quartiles of pack-year history of tobacco exposure (PYH). We assessed cross-sectional associations of smoking with markers of inflammation (C-reactive protein [CRP], Fibrinogen, and InterleukinL-6), arterial stiffness (aortic distensibility by MRI), and subclinical atherosclerosis (SCA) (carotid intima-media thickness [cIMT], and coronary artery calcification [CAC]) by robust linear regression as well as prevalence ratio regression using a generalized linear model and binomial error distribution, after adjustment for covariates. We excluded 23 participants without information on smoking status from the analysis.

Results:
CS comprised 887 (13%, mean age 58yrs), FS 2487 (37%, 63yrs) and NS 3418 (50%, 62yrs) participants. CS were more likely to be younger, male, Caucasian or African American, and have lower LDL-C. The 3 inflammatory markers studied were all elevated in CS. Compared to NS, the adjusted odds ratios for prevalence of CRP≥2 were 1.2 (p<0.001) for former and 1.9 (p<0.001) for CS, respectively. Amongst FS and CS, increased inflammation was noted in the highest quartile of PYH. Aortic distensibility was reduced in CS only, and no association was seen with PYH. However, cIMT and CAC were elevated in both FS and CS, with a greater burden of disease in the highest quartile of PYH.

Conclusion:
These findings suggest a dose-response association between smoking and markers of inflammation as well as measures of SCA. Only current smoking was associated with reduced aortic distensibility.
Abstract 9718: Rising Antibiotic Resistance: Changes in Microbial Patterns in Cardiac Implantable Electronic Device Infections
Authors: Hansen James C , Nayak Hemal M , Moss Joshua D , Beshai John F , Metzl Mark D , Lazar Sorin , Burke Martin C
Published: April 2024

Introduction:
As the number of cardiac implantable electronic devices (CIEDs) implanted has risen, so has the number of CIED infections requiring extraction. We evaluated the type and sensitivity of microbial pathogens associated with CIED infections over a 16-year period.

Hypothesis:
We hypothesized that antibiotic resistance in CIED infections has increased since 1995.

Methods:
We reviewed 202 cases of infected CIEDs requiring extraction. The database was divided into two groups: Group I included the years 1995-2002 and Group II included 2003-2010. Each case was classified as resistant or sensitive. Resistance was present if cultures revealed a methicillin- or vancomycin-resistant organism; otherwise the organism was classified as sensitive. Groups were compared using chi-square analysis, with a p-value < 0.05 considered statistically significant.

Results:
CIED pocket infection or erosion was present in 62.9% of cases, persistent bacteremia with or without obvious endocarditis in 28.7%, and both in 8.4%. Resistance was seen in 13.7% of cases (3/41) in Group I, increasing to 34.2% of cases (55/161) in Group II (p<0.0005). Cultures of hardware (device and/or lead material) increased the yield of resistant organisms to 36.6% (p<0.0001 compared to Group I). The rate of infection with methicillin-resistant
Staph Aureus
(MRSA) more than tripled in Group II (16.8%) as compared to Group I (4.9%). There were a total of 5 in-hospital deaths. In-hospital mortality for resistant infections was 6.4%, compared to 0.7% for sensitive organisms (p<0.05). Patients with organisms identified only from hardware samples represented 15.7% of the cases of resistant infections.

Conclusions:
The incidence of antibiotic-resistant device infections has more than doubled over the past 16 years. Device infections with MRSA have tripled since 1995. Resistant infections are associated with a significantly higher in-hospital mortality. Over 15% of resistant infections were found based on hardware culture alone, stressing the importance of this practice for identifying resistance and tailoring antibiotic therapy for efficacy. More data is needed to aid in the selection of appropriate prophylactic antibiotics for new implants and generator changes.
Abstract 9721:
Tmem100
, a Novel BMP9/10-Dependent Endothelial Gene Essential for Arterial Development and Morphogenesis
Authors: Somekawa Satoshi , Hayashi Hisaki , Sakabe Masahide , Ioka Tomoko , Sato Genki , Inada Ken , Uemura Shiro , Nakagawa Osamu , Saito Yoshihiko
Published: April 2024

Introduction:
Bone morphogenetic protein 9 (BMP9) and BMP10 play critical roles in regulating embryonic vascular development through their endothelium-specific ALK1 receptor. Mutations of the
ALK1
gene cause human hereditary hemorrhagic telangiectasia and pulmonary hypertension, but their downstream functional proteins are largely unknown.

Methods and Results:
We attempted to identify novel endothelial genes downstream of BMP9/10-ALK1 signaling by an mRNA microarray analysis of BMP9-treated human umbilical artery endothelial cells. BMP9 treatment activated expression of various known BMP9/10-regulated genes such as
ID1
up to ten fold. Intriguingly, we also found that BMP9 markedly induced mRNA expression of a previously-uncharacterized gene
TMEM100
more than 100-fold. siRNA knockdown experiments confirmed that
TMEM100
expression by BMP9 or BMP10 was mediated by the ALK1 receptor activation.
TMEM100
encodes
a transmembrane protein that is highly conserved among species, but its expression profiles and physiological significance had not been studied.
Tmem100
was co-expressed with
Alk1
specifically in aortic endothelial cells of mouse embryos (figure, panel A).
Tmem100
null mice die around E10.5 due to impaired differentiation of arterial endothelium and defects of vascular morphogenesis, which phenocopied vascular abnormalities observed in
Alk1
null embryos, indicating a major role of
Tmem100
in the BMP9/10-ALK1 signaling pathway (panel B). Furthermore, expression of activated Notch1 receptor, Notch1-ICD, as well as various Notch-target genes including Hey/Hrt transcription factors significantly decreased in
Tmem100
null embryos, suggesting that
Tmem100
is indispensable for regulation of Notch signaling in proper vascular development.

Conclusion:
We identified
Tmem100
to be a novel endothelial gene essential for arterial development and morphogenesis downstream of BMP9/10-ALK1 signaling.
Abstract 9740: Healthy Lifestyle and Leukocyte Telomere Length In U.S. Women
Authors: Sun Qi , Shi Ling , Prescott Jennifer , Chiuve Stephanie E , Hu Frank B , De Vivo Immaculata , Stampfer Meir J , Franks Paul W , Manson JoAnn E , Rexrode Kathryn M
Published: April 2024

Objectives:
To examine whether healthy lifestyle practices, which are primary prevention measures against major age-related chronic diseases, are associated with longer telomere length.

Design:
Cross-sectional study.

Setting:
The Nurses' Health Study, United States.

Participants:
The population of analysis consisted of 3,355 women who were free of cancer, diabetes, and cardiovascular disease at blood draw in 1990 and were selected as controls in multiple prospective case-control studies within the Nurses' Health Study cohort. Using self-administered questionnaires, these participants provided detailed information on lifestyle practices and dietary habits in 1988 or 1990.

Main outcome measures:
Z scores of leukocyte telomere length were derived among controls in each case-control study. We defined low-risk categories for five major modifiable factors: non-current smoking, maintaining a healthy body weight (18.5 kg/m2 ≤ body mass index < 24.9 kg/m2), engaging in regular moderate or vigorous physical activities (≥150 minutes/week), drinking alcohol in moderation (1 drink/week to <2 drinks/day), and eating a healthy diet (Alternate Healthy Eating Index score in top 50%). We calculated difference (%) of the z scores contrasting low-risk groups with reference groups to evaluate the association of interest.

Results:
Although none of the individual low-risk factors was significantly associated with longer leukocyte telomere length z scores, we observed a significant, monotonic relationship between the number of low-risk factors and the z scores. In comparison with women who had no low-risk factors, the leukocyte telomere length z scores were 15.4%, 21.8%, 23.3%, 24.5%, and 33.1% (P for trend = 0.04) higher for women who had 1 to 5 low-risk factors, respectively.

Conclusion:
Adherence to a healthy lifestyle defined by major modifiable factors may attenuate age-related declines in telomere length.
Abstract 9757: Transcatheter Valve Replacement is a Cost-Effective Alternative to Conventional Surgery in Selected High-Risk Patients
Authors: Gada Hemal , Kapadia Samir R , Tuzcu E M , Svensson Lars G , Marwick Thomas H
Published: April 2024

Background:
Transfemoral transcatheter aortic valve replacement (TAVR) is cost-effective for management of severe aortic stenosis (AS) in patients with unacceptable risk for aortic valve replacement (AVR). However, the relative cost-effectiveness of TAVR and tissue AVR is ill-defined in high-risk patients where surgery is an option. We developed a Markov model to inform the choice between transfemoral TAVR and AVR in high-risk patients.

Methods:
A Markov model was developed to examine the progression of patients between health states, defined as peri- and post-procedural, post-complication, and death. The mean and variance of risks, transition probabilities, utilities and cost of TAVR and AVR were derived from meta-analysis of relevant registries, studies and trials. Outcome and cost were derived from 10,000 simulations. Sensitivity analyses were based on the likelihood of mortality, stroke, and other commonly observed outcomes. Further analyses evaluated situations thought to favor tissue AVR or TAVR.

Results:
In the reference case (age 80, peri-operative mortality of transfemoral TAVR and AVR 5.8 vs 9.1%, annual mortality 22.2 vs 22.5%), the utility of TAVR was greater than AVR (1.71 vs 1.64 QALY). As the cost of TAVR was greater than AVR ($26,176 vs $19,361), the incremental cost-effectiveness ratio (ICER) was $97,357/QALY. In sensitivity analyses, variations in stroke, peri-operative and annual mortality are the main drivers of variation in health outcomes. The current risk profile of transfemoral TAVR offered net health benefits when peri-operative AVR mortality was >5.2%, or stroke post-TAVR was <11.3% (Figure). In a scenario analysis based only on operable PARTNER patients (Cohort A), QALYs for TAVR and AVR were 1.69 and 1.63, with an ICER of $70,633/QALY.

Conclusion:
TAVR may provide net health benefits at acceptable cost in selected high-risk patients among whom AVR is the current procedure of choice.
Abstract 98: Initiation of Large-Volume, Ice-Cold Saline Infusion During Initial Resuscitation Attempts for Out-of-Hospital Cardiac Arrest Results in Near-Target Temperatures for Therapeutic Hypothermia Upon Emergency Department Arrival
Authors:   NYC Project Hypothermia Working Group, Freese John
Published: April 2024

Background:
New York City Project Hypothermia is a collaborative effort involving the Fire Department of New York (FDNY), Greater New York Hospital Association, Health and Hospitals Corporation, the Regional Emergency Medical Advisory Committee, and the New York State Department of Health. As part of this effort, the FDNY implemented a pilot protocol in the New York City 9-1-1 System on August 1, 2010 that introduced the induction of therapeutic hypothermia during initial resuscitation efforts via large-volume, pressure infused, ice-cold saline administration.

Purpose:
We sought to assess the effects of the intra-arrest initiation of an infusion of up to 30cc/kg of ice-cold saline on core body temperature for out-of-hospital cardiac arrest (OOHCA).

Methods:
A convenience sample of out-of-hospital cardiac arrest patients for whom core temperature monitoring via esophageal temperature probes was available were analyzed.

Results:
There were a total of 78 patients for whom core temperature (esophageal) data was available both at the time hypothermia induction and upon ED arrival. Eight patients (10.3%) were reported to have developed clinical signs of pulmonary edema during the infusion and were excluded from this analysis due to the discontinuation of the large-volume infusion. Among the remaining 70 patients, an average of 1,361mls of ice-cold saline was administered prior to emergency department arrival. The average initial temperature for these patients at the time hypothermia induction was 35.1
o
C (range 32.7-38.0
o
C). The average temperature reduction as a result of the large-volume, ice-cold saline infusion was -0.92
o
C, with an average core temperature upon emergency department arrival of 34.2
o
C.

Conclusion:
Large volume, ice-cold saline infusion during initial resuscitation efforts allows patients to arrive in the emergency department with a core temperature near the target range for therapeutic hypothermia. Further study is needed to assess the effects of early induction of hypothermia on immediate and long-term survival.
Abstract 9816: Use of the Wearable Cardioverter Defibrillator and Survival After Coronary Artery Revascularization in Patients with Left Ventricular Dysfunction
Authors: Zishiri Edwin T , Cronin Edmond , Williams Sarah , Blackstone Eugene , Ellis Steven , Smedira Nicholas , Gillinov Marc A , G Gonzalez-Stawinski , Douglas Johnston , Roselli Eric , Glad Jo Ann , Szymkiewicz Steven J , Lindsay Bruce D , Chung Mina K
Published: April 2024

Background:
ICD implantation for primary prevention of sudden cardiac death (SCD) is typically deferred in the immediate post revascularization period due to reimbursement restrictions, but mortality risk may be highest early after cardiac procedures. The wearable cardioverter-defibrillator (WCD) is a noninvasive device capable of protection from SCD and may be useful during this period.

Objective:
To determine if there is a difference in survival of patients with LVEF≤35% from a national registry using a WCD after revascularization compared to patients with LVEF≤35% discharged after surgical or percutaneous revascularization without the WCD.

Methods:
Kaplan-Meier survival, Cox proportional hazards and propensity score matched analyses were performed to determine if survival differed in patients discharged after surgical (CABG) or percutaneous (PCI) coronary revascularization with LVEF≤35% from a national database of WCD users (N=809) compared to patients with LVEF≤35% from surgical and interventional registries at the Cleveland Clinic (N=4149).

Results:
Survival curves showed higher early compared to late mortality in the non-WCD groups with 90-day mortality after CABG of 3% in WCD users vs. 7% in non-users and after PCI 2% in WCD users vs. 10% in the non WCD users. WCD use was associated with an adjusted 57% lower risk of death (p<0.0001) among post-PCI patients over a mean follow up of 3.1±2.3 years and an adjusted 38% lower risk of death in post CABG patients (p value 0.048) over a mean follow up of mean follow-up 3.2 ± 2.5 years.
Limitations:
Adjustment for co-morbidities was limited in this single center vs. national database study.

Conclusions:
In patients with LVEF <35%, WCD users did not demonstrate the high early phase mortality after revascularization that was seen in the non-WCD users. These findings provide a rationale for additional studies of WCD use after revascularization in patients with LV dysfunction.
Abstract 9849: Aerobic Exercise Improves Endothelial Dysfunction in Pre-Diabetes Patients
Authors: Sen Sabyasachi , Lagoy Anne , Islam Ashequl , Witkowski Sarah
Published: April 2024

Current literature confirms presence of endothelial cell dysfunction in diabetes compared to non-diabetes state. However there is lack of data on endothelial function in Pre-diabetes (defined as per
Diabetes Care, Clinical Guideline, Jan'11
).

Methods:
We selected exercise-naive patients, 20-70 yrs, BMI 25-34.9, n=20 in each group and studied their endothelial function after 150min/week of aerobic exercise (similar to Diabetes Prevention Program) and after non exercise phase (6wks phase each), in a cross over design with a 4 wk wash-out period between the 2 groups. For endothelial function assessment we looked at, 1. flow mediated dilatation (FMD of brachial artery), 2. CD34/KDR +ve cell count from peripheral blood derived mononuclear cell fraction at day0 by Flow cytometry (FACS) 3. endothelial progenitor cell (EPC) associated colony-forming units (Hill-CFU) at day5 of culture, 4.endothelial bio-inflammatory markers and BP, fasting lipids, insulin, glucose. We also looked at gene expression profile of critical endothelial function genes in CD34/KDR+ve cells.

Results:
FMD studies (undertaken by 3 observers, blinded to glycemic status) showed, mean FMD in non-exercise group of 5.7+0.6% and post exercise it improved to 11.2±0.9%. Both CFU estimation, at day5 and CD34/KDR +ve cells estimation at day0 showed significant increase in numbers following exercise. There was no weight loss noted between 2 groups, however, there was statistically significant reduction in leptin, IL-6, TNFα, fasting Triglyceride, LDL and ApoB levels. Insulin sensitivity (HOMA) improved in the exercise group. Gene expression analysis of CD34+ve cells showed decrease of eNOS and increase of PECAM-1 in non-exercise which improved significantly following exercise, with no change in von-Willebrand's factor.

Summary:
Prediabetic patients have significant endothelial dysfunction, similar to patients with diabetes. In this population, FMD measurements and CD34/KDR+ve cell number and gene profile assays along with usual biochemical markers can serve as robust bio-markers for monitoring endothelial cell dysfunction.

Conclusion:
Pre-diabetic state is associated with significant endothelial dysfunction which can be improved, by undertaking regular aerobic exercise.
Abstract 9877: Novel Clinical Risk Score for the Prediction of Cardiac Events in Patients with Vasospastic Angina -A Report from the Nationwide Multi-Center Registry by the Japanese Coronary Spasm Association
Authors: Takagi Yusuke , Yasuda Satoshi , Tsunoda Ryusuke , Ogata Yasuhiro , Seki Atsushi , Sumiyoshi Tetsuya , Matsui Motoyuki , Goto Toshikazu , Tanabe Yasuhiko , Sueda Shozo , Sato Toshiaki , Ogawa Satoshi , Kubo Norifumi , Momomura Shin-ichi , Ogawa Hisao , Shimokawa Hiroaki
Published: April 2024

Background:
Previous studies demonstrated various predictive factors of cardiac events (e.g., out-of-hospital cardiac arrest) in patients with vasospastic angina (VSA). However, the useful score to predict cardiovascular events in VSA patients needs to be developed. We thus aimed to develop a novel clinical risk prediction score for VSA patients.

Methods:
The VSA database of the nationwide multi-center registry study by the Japanese Coronary Spasm Association (n=1,429; median 66 years; median follow-up of 32 months) was utilized for score derivation. Multivariable Cox proportional hazard model was used to select the correlated factors of major adverse cardiac events (MACE) including cardiac death, non-fatal myocardial infarction, unstable angina and heart failure. They were subsequently weighted according to the adjusted hazard ratio (HR) and integrated into the scoring system.

Results:
Six variables selected following Cox model were weighted; smoking (2 points), angina at rest alone (2 points), life-threatening arrhythmia during angina (2 points), multivessel spasm (2 points), organic coronary stenosis >50% (2 points) and ST elevation during angina (1 point). According to the total score, 3 strata of risk were defined; low (score 0-3, n=713), intermediate (score 4-6, n=666) and high (score 7-9, n=50). The incidence of MACE in the low-, intermediate- and high-risk patients were 2.8%, 8.3% and 20.0%, respectively (P<0.001). Kaplan-Meier curve for MACE among the 3 risk groups showed prognostic utility of the scoring system throughout the follow-up period (low vs. intermediate, HR 3.04, 95% CI 1.82-5.07, P<0.001; low vs. high, HR 8.13, 95% CI 3.80-17.37, P<0.001) (
Figure
). The C-statistic for the score predicting MACE was 0.67.

Conclusions:
We developed a novel scoring system that provides the stratification of cumulative risk of cardiac events in VSA patients, which is clinically relevant in the triage and management of the disorder.
Abstract 9890: The Short- and the Long-Term Outcomes of Percutaneous Coronary Intervention for Chronic Total Occlusions in Elderly Patients
Authors: Tanaka Yutaka , Takeshita Satoshi , Matsumi Junya , Mizuno Shingo , Sugitatsu Kazuya , Yamanaka Futoshi , Oosaka Yumiko , Nomura Yu , Shishido Koki , Suenaga Hidetaka , Murakami Masato , Takahashi Saeko , Saito Shigeru
Published: April 2024

Introduction:
We investigated the safety and the efficacy of percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) in elderly patients.

Methods:
Between 2005 and 2009, 301 consecutive patients underwent PCI for a total of 323 CTO lesions. The short and the long-term outcomes of PCI were retrospectively evaluated by comparing patients with ≥ 75 years (n = 71, 23.6%) and those with < 75 years (n = 230, 76.4%).

Results:
Procedural success was achieved in 78.7% of the patients in the elderly group and 78.2% in the younger group (P = 0.73). No significant differences were observed in the incidences of procedural-related complications between the two groups (2.8% vs. 5.2%; P = 0.40). At a mean follow-up of 3.1 years, the incidence of major adverse cardiac events (MACE: all-cause death, myocardial infarction and target lesion revascularization [TLR]) was significantly higher in the elderly group (27.8% vs. 5.4%; P < 0.001). TLR was not significantly different between the groups (12.4% vs. 19.2%; P = 0.64). When comparing patients with successful and failed PCI among elderly group, incidences of MACE did not show significant differences (54.0 vs. 66.0%; P = 0.53). However, those with successful PCI showed significantly improved cardiac survival compared to those with failed PCI (92.2% vs. 72.0%; P = 0.011), the level of which was similar to those observed in the younger group irrespective of their procedural success (98.7% with successful PCI and 100% with failed PCI). After multivariate analysis, only successful PCI was found to be the independent factor associated with a reduction of cardiac death in the elderly group (HR: 0.134; 95% CI: 0.022-0.815; P = 0.029).

Conclusions:
This retrospective study demonstrates that PCI for CTO lesions in elderly patients is associated with the improved cardiac survival after successful PCI. PCI for CTO lesions may become a viable treatment strategy even in elderly patients.
Abstract 9897: Impact of Extracorporeal Membrane Oxygenation and Cardiopulmonary Resuscitation on Norwood Procedure Outcomes: Data from the Single Ventricle Reconstruction Trail
Authors: Ravishankar Chitra , Tabbutt Sarah , Allen Kerstin , Cooper David S , Frank Deborah U , Frommelt Peter C , Ghanayem Nancy S , Goldberg Caren S , Graham Eric M , Kirsh Joel A , Dent Krawczeski Catherine , Lai Wyman W , Lewis Alan , Lodge Andrew J , Mahony Lynn , Simsic Janet , Sleeper Lynn A , Stylianou Mario , Wang Yanli , Laussen Peter ,   for the Pediatric Heart Network Investigators
Published: April 2024

Background:
Extracorporeal membrane oxygenation (ECMO) and cardiopulmonary resuscitation (CPR) are reported risk factors for worse outcome after the Norwood procedure (NP). The Single Ventricle Reconstruction (SVR) trial randomized infants with hypoplastic left heart syndrome to a modified Blalock-Taussig shunt (MBTS) or right ventricular to pulmonary artery shunt (RVPAS). We explored associations between ECMO and/or CPR with death and transplant.

Methods:
Outcomes for 549 SVR patients using the shunt in place at end of the NP (MBTS 268, RVPAS 281) were compared among: CPR alone (CPR, n=37), ECMO alone (ECMO, n=49), ECMO required to regain circulation after CPR (E-CPR, n=36) and neither CPR nor ECMO (“none”, n=427). Cox proportional hazards regression with a time-dependent group indicator was used to model time to death or transplant. The interaction of patient group and shunt type was also examined.

Results:
Mean follow-up was 2.7 ± 1.9 years. Gestational age, age at surgery, size of ascending aorta, presence of significant tricuspid regurgitation, systolic function and shunt type were similar among the 4 groups. Low birth weight was more common in CPR or E-CPR groups (p<.001). Patients receiving CPR, ECMO or E-CPR had a higher incidence of transplant or death (p<.0001). With adjustment for surgeon and birth weight, interaction analysis showed poorer outcome with MBTS in the “none” group but not in the E-CPR group (interaction p = .014). The hazard ratio for MBTS vs. RVPAS in E-CPR was 0.48 (95% CI 0.21, 1.11) vs. 1.54 (95% CI 1.04, 2.28) for “none”. A similar pattern was seen with ECMO (interaction p = .047). A differential effect of shunt type was not observed for CPR vs. “none” patients.

Conclusions:
Patients requiring CPR and/or ECMO after the Norwood procedure have significantly increased early mortality and/or transplant and remain at risk for attrition remote from the initial event. The RVPAS was not found to be superior to the MBTS in patients requiring ECMO or E-CPR.
Abstract 9902: Food Restriction Induces Cardiac BDNF/TrkB Signaling and Improves Physical Activity in Obese Mice
Authors: Kanda Tsugiyasu , Mizuno Takuro , Sakamoto Daisuke
Published: April 2024

Introduction
-Brain-derived neurotrophic factor (BDNF) gene is not only expressed in neuron but cardiac muscle and modulate cardiac function. We hypothesized that cardiac expression of BDNF can be induced by food restriction in obesity and that induced BDNF signaling can be beneficial in cardiac dysfunction.

Methods
-Obese KKAy mice were ad libitum as a control (CF) or 60% restriction of that eaten by ad libitum (RF). Mice were sacrificed on day 0, 7, 28, and 84 after food restriction.

Results
-Body weight and liver weight / body weight ratio in RF were significantly lower than that in CF on days 7, 28 and 84 (P<0.05) but heart weight/ body weight ratio were not changed between mice with CF and RF. Comparative expression of cardiac BDNF mRNA in RF was significantly higher than that in CF (1.2+0.3 vs. 0.8+0.2, P<0.05). Cardiac expression of TrkB in RF was significantly increased than that in CF on day 84. Cardiac expression of brain natriuretic peptide was significantly lower in mice with FR compared with those with CF. Hippocampal expressions of BDNF in RF and were significantly increased compared with those in CF on days 28 and 84. Hippocampal expression of TrkB in RF was significantly higher than in CF on days 28 and 84. Hippocampal weight / body weight ratio was also significantly higher in mice with RF compared with those with CF on days 28 and 84. Daily activity in RF was significantly increased compared with that in FF on day 28 (P<0.05).

Conclusions
-Food restriction can induce cardiac BDNF/TrkB signaling with the increase of daily activity in obese mice. Cardiac BDNF plays a role in recovery from obesity. These data indicate that induced expression of BDNF/TrkB signaling can improve cardiac dysfunction in obese mice with the combination of induced expression of hippocampal BDNF/TrkB.
Abstract 9930: Cost Effectiveness of Improved Acute Myocardial Infarction Treatment in China: Projections From the Coronary Heart Disease Policy Model-China
Authors: Wang Miao , Moran Andrew , Liu Jing , Coxson Pamela , Heidenreich Paul , Gu Dongfeng , He Jiang , Goldman Lee , Zhao Dong
Published: April 2024

Background:
Currently, only 50% of ST-elevation myocardial infarction (STEMI) receive reperfusion therapy in China, and four standard oral medications-aspirin, beta blocker, statins, and angiotensin converting enzyme inhibitor-are utilized together in only 44-48% of hospitalized patients with acute myocardial infarction (AMI). This study was to simulate the effectiveness and costs of AMI treatment after improving utilization of selected standard AMI treatments in China by using the coronary heart disease(CHD) Policy Model-China.

Methods:
The CHD Policy Model-China is a computer-simulation, Markov model of cardiovascular disease which could simulate the incidence trend of AMI, cost and effectiveness of treatments. Current utilization of selected AMI interventions in China were obtained from the Bridging the Gap in Coronary Heart Disease Secondary Prevention in China Project. In eligible patients, 100% utilization was simulated for 1) four standard oral drugs for all AMI, 2) unfractionated heparin for non-ST-elevation myocardial infarction(NSTEMI), 3) reperfusion using percutaneous intervention(PCI) or thrombolysis for STEMI, and 4) early invasive PCI for NSTEMI.

Results:
The incremental cost-effectiveness ratio (ICER) of improving utilization of any of the selected acute in-hospital AMI treatments ranged from $2,977 to $24,558 per quality-adjusted life year (QALY) gained. Improving utilization of four standard oral medications in 100% of AMI patients by itself could save about 9,000 CHD deaths each year. Achieving 100% reperfusion in eligible STEMI patients with PCI would prevent the most CHD deaths (49,000 /year) and achieve the highest QALY increase (177,000/year). The ICER of achieving 100% reperfusion in eligible STEMI patients with PCI is 2.4 time higher than with thrombolysis, but could prevent 3 times CHD death than the latter. Only the ICER of PCI for NSTEMI was above the pre-determined cost effectiveness threshold for China ($7,974 per QALY gained).

Conclusions:
With the exception of PCI for NSTEMI, improved utilization of any of the acute in-hospital MI treatments was projected to be highly effective, and relatively low cost. Improving utilization of acute AMI treatments will be a useful strategy to prevent CHD deaths in China.
Abstract 9934: Levels of Plasma Pentraxin 3 Predict Presence of Thin-cap Fibroatheroma in Patients with Stable Angina Pectoris: Assessment by Optical Coherence Tomography
Authors: Koga Seiji , Ikeda Satoshi , Nakata Tomoo , Yoshida Takeo , Takeno Masayoshi , Koide Yuji , Maemura Koji
Published: April 2024

Background:
Thin-cap fibroatheroma (TCFA) is the primary type of rupture prone plaque, but biomarkers predicting it are not established. Recently, pentraxin 3 (PTX3) has been shown to be a novel biomarker specific to vascular inflammation. The aim of this study was to clarify the association between plasma PTX3 level and TCFA as determined by optical coherence tomography (OCT) in patients with stable angina pectoris (SAP).

Methods:
Thirty-four patients with SAP who underwent OCT at de novo culprit lesions before percutaneous coronary intervention were evaluated. TCFA was defined as a plaque with lipid contents in >90°and with thinnest part of the fibrous cap measuring <70μ m. Plasma PTX3 and serum high sensitive C-reactive protein (hsCRP) were measured among these patients. Plasma PTX3 level was categorized into low (< 25th percentile), intermediate (25th to 75th percentiles), and high (> 75th percentile) groups.

Results:
Fourteen patients with TCFA and 20 patients without TCFA were identified. Levels of PTX3 (median [interquartile range]) were significantly greater in patients with TCFA than without TCFA (4.66 [2.44 - 6.80]) vs. 2.60 [1.79 - 3.18] ng/mL; p = 0.009). Levels of hsCRP were comparable between the two groups. PTX3 level significantly inversely correlated with fibrous cap thickness (r = -0.53, p = 0.009), but hsCRP did not. The frequency of TCFA was 22, 29, and 88% in low, intermediate, and high PTX3 group, respectively (p = 0.009). Univariate analysis revealed that hypercholesterolemia, statin use, and level of PTX3 were related to the presence of TCFA. Multivariate logistic regression analysis in these factors showed that plasma PTX3 level was the significant independent factor associated with TCFA existence (OR, 1.99; 95%CI, 1.10 - 3.58; p = 0.023). The area under the receiver-operating characteristics curve for PTX3 level for prediction of TCFA was 0.766 (p = 0.009). The optimal cut-off value of PTX3 for predicting TCFA was 2.88 ng/mL (sensitivity 71%, specificity 70%).

Conclusions:
Plasma PTX3 level was associated with the presence of TCFA and thinner fibrous cap thickness at coronary culprit lesions in patients with SAP. These findings suggest that plasma PTX3 might be a useful marker reflecting the plaque vulnerability.