bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11983: Delayed Inhalation of Hydrogen Mitigates Neurological Dysfunction in a Porcine Model of Cardiac Arrest and Cardiopulmonary Resuscitation
Authors: Yang Zhengfei , Yu Tao , Wen Cai , Zhai Xiaozhu , Peberdy Mary Ann , Ornato Joseph P , Tang Wanchun
Published: April 2024

Introduction:
Immediate inhalation of hydrogen (H
2
) has been demonstrated to improve post-resuscitation (PR) neurological dysfunction. However, early applying inhaled H
2
is not practical especially in out of hospital cardiac arrest because of the safety issue. In the present study, we investigated the effects of delayed treatments with H
2
on post resuscitation neurological function in a porcine model of prolonged cardiac arrest (CA).

Hypothesis:
Delayed inhalation of H
2
mitigates neurological dysfunction after resuscitation in a CA porcine model.

Methods:
Eighteen male domestic pigs weighing 39±2 kg were utilized. Ventricular fibrillation (VF) was induced electrically and CPR was initiated after 10 mins of untreated VF. All the animals were resuscitated successfully and randomized into two groups immediately following resuscitation: delayed inhalation of H
2
(DH group, N=9) or inhalation of room air (C group, N=9). Animals in the DH group were ventilated with 2% H
2
/21% oxygen from 2h post resuscitation (PR) to PR 4h. Serum levels of S100B and neuron-specific enolase (NSE) were measured by ELISA at baseline and PR 360 min. The neurological deficit score (NDS) and survival were evaluated daily for a total of 72 hours.

Results:
Better survival duration and NDS at 24h, 48h and 72h were observed in the DH group animals compared with those of the C group (Table). The serum levels of S100B and NSE were significantly lower in the DH group when compared with the C group (Figure).

Conclusion:
Delayed treatment of H
2
mitigates neurological injury and improves neurological dysfunction after resuscitation.
Abstract 11985: The Role of Bystanders in Timely CPR and Related Outcomes After Out-of-Hospital Cardiac Arrest
Authors: Park Gwan Jin , Song Kyoung Jun , Ro Young Sun , Kim Tae Han , Park Yong Joo , Park Jeong Ho , Hong Ki Jeong , Lee Kyung Won , Shin Sang Do
Published: April 2024

Objective:
Without cardiopulmonary resuscitation (CPR), cardiac arrest survival declines 5-10% for every minutes. But, there is a limit to reduce the time from collapse to Emergency medical service (EMS) arrival. This study aimed to examine the association between the time interval from collapse to CPR by EMS providers and related outcomes in patients who received bystander CPR.

Methods:
A population-based observational study was conducted with out-of-hospital cardiac arrests (OHCA) of cardiac etiology who were witnessed by laypersons in Korea between 2012 and 2014. Exposure variable was the proportion of the time interval from collapse to CPR by EMS providers categorized into quartile groups: group 1 (time < 4 min), group 2 (4 ≤ time < 8), group 3 (8 ≤ time< 15), group 4 (15 ≤ time < 30). Primary endpoint was time interval from collapse to CPR by EMS providers and secondary endpoint were survival to discharge and survival with favorable neurological outcome (Cerebral Performance Category (CPC) 1-2). Multivariable logistic regression analysis was performed. The final model was performed to evaluate interactive effect between bystander CPR and the time interval from collapse to CPR by EMS providers.

Results:
A total of 15,354 OHCAs were analyzed. Bystander CPR was performed in 8,591 (55.95%). The survival to discharge rate was 10.6% (1632) and favorable neurological outcome was 6.5% (996). In an interaction model of bystander CPR patients, AORs (95% CIs) for survival to discharge rate were 0.89 (0.66-1.20) in group 2, 0.76 (0.57-1.02) in group 3, 0.52 (0.37-0.73) in group 4 compared with group 1. For favorable neurological outcome, AORs were 1.12 (0.77-1.62) in group 2, 0.90 (0.62-1.30) in group 3, 0.59 (0.38-0.91) in group 4.

Conclusion:
Despite of poor ambulance response time, patients who received bystander CPR would show favorable outcomes. Prompt delivered bystander CPR was strongly associated with increased survival.

Keywords:
Out-of-hospital cardiac arrest; Cardiopulmonary resuscitation; Emergency medical services
Abstract 12056: Computational Fluid Dynamics Description of Blood Flow in a Bidirectional Glenn Shunt Supplemented With a Modified Blalock-Taussig Shunt: Relevance to Thrombosis and Power Loss
Authors: Aslan Seda , Ross-Ascuitto Nancy , Guillot Martin , Ascuitto Robert
Published: April 2024

Introduction:
A bidirectional Glenn shunt (BGS) has been supplemented with a modified Blalock-Taussig shunt (BTS), to enhance growth of the pulmonary arteries (PAs). However, the hemodynamics is incompletely understood.

Hypothesis:
High velocity BTS flow imposed on low velocity BGS flow can create secondary currents (vortices) in the PAs conducive to clot deposition and power dissipation.

Methods:
We employed a computational model (Fluent) of pulsatile flow (viscosity 5 cPa-s), using the finite volume method, and a schematic representation of a BGS with a BTS, to determine velocity field, wall shear stress (WSS) and power (W) efficiency (PE). The region studied included the internal jugular, subclavian and innominate veins, BGS (12.5 mm), BTS (4 mm) and PAs (9 mm). Vessel sizes and flow rates were derived from reported values. Flow rates were fixed at the inlet of the veins, and in the BGS was 1L/min. Aortic pressure (82/42 mmHg) was used at the inlet to the BTS, and a mean pressure (12 mmHg) at the outlets of the PAs.

Results:
Fig 1 shows velocity magnitude at peak systole. The BTS jet (red) enters the LPA, where it gives rise to dissipative counter-rotating velocity fields, which augment local WSS. Fig (2) shows the velocity fields (arrows) in cross-sectional planes where the BGS and BTS connect to the PAs. The high WSS (350 Pa) is sufficient (> 100 Pa) to initiate platelet aggregation leading to thrombus formation. PE (1-W
loss
/W
in
) for the BGS alone was 97%; whereas, with the BTS it decreased to 29%. The BTS increased BGS pressure, 12.3 to 14.0 mmHg.

Conclusion:
Supplementing a BGS with a BTS can: 1) elevate BGS pressure, 2) create regions at risk for thrombus formation and 3) worsen power loss.
Abstract 12066: TIMP3 and CHADL Mutations Are Common in Turner Syndrome Aortopathy
Authors: Silberbach Michael , Corbitt Holly , Krupp Diedre , O’Roak Brian ,   GenTAC Investigators, Maslen Cheryl
Published: April 2024

Introduction:
Turner syndrome (TS) is caused by the loss of the second sex chromosome, which occurs in approximately 1 in 2,000 female births. TS alone is an independent risk factor for aortic enlargement. 25 to 50% of those with TS also have a bicuspid aortic valve (BAV) which is present in most who have aortic dissection and rupture.

Methods:
We used whole exome sequencing to study the genes of 188 TS subjects with BAV (88 cases) or normal aortic valves (100 controls). Aorta diameters as markers of aortopathy severity converted into Z-scores were utilized as covariates with BAV status, and as a sole predictor of genetic variation. Enlarged aorta was defined as an ascending aorta Z-score > 2. Statistical analyses employed a kernel gene-based method, SKAT-O.

Results:
TS girls and women with BAV had significantly higher ascending aortic Z-scores than those without BAV (1.95 ± 1.97 vs 0.55 ± 1.01, t-test p= 1.6 x 10
-5
).Mutations in
TIMP3
and
CHADL
achieved exome-wide significance for association with BAV/aortic dilatation (p=1.6x10
-6
and 1.1x10
-6
, respectively).
TIMP3
significance increased when aortic root Z-scores were included as a continuous covariant with BAV status (p=2.3x10
-7
). Overall, 30.7% of those with aortic dilatation had mutations predicted by CADD scores to be deleterious in
TIMP3
(8 individuals),
CHADL
(4 individuals), or both (4 individuals). Those with mutations in both genes were more likely to have enlarged aortas than those with 1 or none (chi-squared p=2.8x10
-3
).

Discussion and conclusions:
BAV is known to be associated with aortopathy in TS. We found that
TIMP3
and
CHADL
mutations occur commonly with those findings
.
TIMP3 is an inhibitor of several aortic matrix metalloproteinases, a group of peptidases that degrade extracellular matrix (ECM). CHADL is a collagen binding protein that regulates collagen fiber formation. Collagens are necessary for aortic structural integrity. We hypothesize that mutations in
TIMP3
and
CHADL
disrupt the critical balance between ECM creation and degradation, thereby compromising aortic strength. There appears to be a synergy between TIMP3 and CHADL functions that may be involved in both BAV development and aortopathy. Both TIMP3 and CHADL may serve as biomarkers and pharmacologic targets for aortic disease in TS.
Abstract 12105: Temperature Variability During Targeted Temperature Management is not Associated With Neurological Outcomes following Cardiac Arrest
Authors: Nayeri Arash , Bhatia Nirmanmoh , Holmes Benjamin , Borges Nyal , Armstrong William , Xu Meng , Farber-Eger Eric , Wells Quinn , McPherson John
Published: April 2024

Introduction:
Recent studies on comatose survivors of cardiac arrest undergoing targeted temperature management (TTM) have reported similar outcomes at multiple target temperatures. However, details regarding core temperature variability during TTM and its prognostic implications remain unknown.

Hypothesis:
Increasing core temperature variability during TTM will predict poor neurological outcomes.

Methods:
We analyzed a prospectively collected cohort of 242 consecutive comatose survivors of cardiac arrest treated with TTM at a tertiary care hospital between 2007 and 2014. Core temperature variability was defined as the statistical variance (i.e. standard deviation squared) amongst all core temperature recordings during the maintenance phase of TTM. Poor neurological outcome at hospital discharge, defined as a Cerebral Performance Category (CPC) score >2, was the primary outcome. Death prior to hospital discharge was assessed as the secondary outcome.

Results:
Baseline patient characteristics are reported in
Table 1.
A poor neurological outcome was observed in 147 (61%) patients and 136 (56%) patients died prior to hospital discharge. In multivariable logistic regression, increased core temperature variability was not associated with increased odds of poor neurological outcomes (OR 0.38, 95% CI 0.11-1.38, p=0.142) or death (OR 0.43, 95% CI 0.12-1.53, p=0.193) at hospital discharge.

Conclusions:
In this study, individual core temperature variability during TTM was not associated with poor neurological outcomes or death at hospital discharge.

Table 1.
Baseline characteristics and clinical features. Data are presented as median (IQR) for continuous variables and number (percentage) of patients for categorical variables. N represents the number of non-missing values.

CPR, cardiopulmonary resuscitation; ROSC, return of spontaneous circulation; TTM, targeted temperature management.
Abstract 12123: Periodicity-Analysis of a Photoplethysmography Signal May Support Pulse Detection in a Few-Second Compression-Pause During Cardiopulmonary Resuscitation
Authors: Wijshoff Ralph , Haarburger Christoph , Muehlsteff Jens , Noordergraaf Gerrit Jan
Published: April 2024

Introduction:
Pulse checks during cardiopulmonary resuscitation (CPR) are typically performed by manual palpation, which is unreliable and can interrupt compressions for longer than the recommended 10 s.

Hypothesis:
Presence of a spontaneous pulse can be detected in a compression-free photoplethysmography (PPG) signal within 5 s, by assessing the periodicity of the signal.

Methods:
We measured nasal PPG signals in 11 pigs during periods of 10-min baseline, arrest induction, 20-min 30:2 CPR, defibrillation, and 20-min post return of spontaneous circulation (ROSC), with aortic pressure and thoracic impedance as references.

We annotated pulse presence and obtained compression-free windows of PPG signals from the ventilation pauses and by segmenting the baseline and post-ROSC phases in 4-s non-overlapping windows.

Pulse presence was detected by assessing signal periodicity in the autocorrelation function (ACF), which compared a window of the PPG signal to time shifts of this window. Windows with pulse had local maxima in the ACF when a time shift aligned the pulses in both windows (Fig. 1a). Pulseless windows had unstructured ACFs (Fig. 1b). We assessed periodicity via the maximum prominence of all peaks at non-zero shift in the ACF. Prominence is the amplitude relative to the largest surrounding minimum (Fig. 1a,b). We used the prominence and related features in a logistic regression classifier to quantify pulse absence and presence on a continuous scale from 0 to 1 (Fig. 1c). We trained and validated the classifier via five-fold cross-validation, regarding a classifier output of ≥0.5 as indicative of pulse presence.

Results:
Sensitivity was 97.1% and specificity was 96.2%.

Conclusions:
Periodicity analysis allows for pulse detection in PPG signals within 5 s. This could be used during existing ventilation pauses to prepare for a faster pulse check or avoid an unnecessary pulse check.

Fig. 1:
(a) ACF for pulse presence. (b) ACF for pulse absence. (c) Classifier output.
Abstract 12151: PCSK9 Mediates Atherogenesis
Authors: Sun Hua , Krauss Ronald M , Teng Ba-bie
Published: April 2024

Background:
Proprotein convertase subtilisin kexin type 9 (PCSK9) negatively regulates the low-density lipoprotein (LDL) receptor (LDLR), resulting in increased LDL cholesterol levels. We have suggested that PCSK9 regulates apolipoprotein B (apoB) metabolism via an autophagic process that is independent of the LDLR. Furthermore, whether PCSK9 plays a causal role in atherogenesis independent of LDLR has been controversial. Here, we investigated the molecular mechanisms by which PCSK9 modulates autophagy and the LDLR-independent effects of PCSK9 on atherogenesis.

Methods and Results:
Deletion of the PCSK9 gene from atherosclerosis prone LDb (
Ldlr-/-Apobec1-/-)
mice resulted in substantially less atherosclerosis (> 4-fold), as well as a substantial reduction of plasma apoB, lipids, and triglyceride-rich lipoproteins, but increased HDL particles. The triple knockout mice had a decreased rate of apoB secretion resulting from increased autophagic flux. The deletion of PCSK9 also had profound influences on aortic endothelial cell response to exposure to LDL. LDL associated with PCSK9 increased the expression of TLR2, Lox-1, ICAM-1, CCL2, CCL7, IL-6, IL-1β, Beclin-1, p62, and TRAF6, compared to LDL without PCSK9.

Conclusion:
Deletion of PCSK9 markedly decreases apoB production by increasing autophagic flux. The absence of PCSK9 results in decreased lipid levels and marked reduction of atherosclerosis, independent of LDLR. The influence on atherogenesis is in part due to the direct effects of PCSK9 on endothelial cell receptors and on proinflammatory and autophagy molecules. These findings suggest that there may be clinical benefits of PCSK9 inhibition due to mechanisms unrelated to increased LDLR activity.
Abstract 12229: Bundle Branch Reentrant Ventricular Tachycardia: Novel Genetic Mechanisms in a Life-Threatening Arrhythmia
Authors: Roberts Jason D , Gollob Michael H , Young Charlie , Connors Sean P , Gray Chris , Wilton Stephen B , Green Martin S , Zhu Dennis W , Hodgkinson Kathleen A , Poon Annie , Li Qiuju , Orr Nathan , Tang Anthony S , Klein George J , Wojciak Julianne , Campagna Joan , Olgin Jeffrey E , Badhwar Nitish , Vedantham Vasanth , Marcus Gregory , Kwok Pui-Yan , Deo Rahul C , Scheinman Melvin M
Published: April 2024

Introduction:
Bundle branch reentrant ventricular tachycardia (BBRVT) is a life-threatening ventricular arrhythmia occurring secondary to macroreentry within the His-Purkinje system. Although classically associated with dilated cardiomyopathy, BBRVT may also occur in the setting of isolated, unexplained conduction system disease.

Hypothesis:
Idiopathic BBRVT may be secondary to genetic mutations associated with conduction system disease.

Methods & Results:
We identified 6 cases of BBRVT associated with normal biventricular size and function from 6 centers across North America. Study participants were screened for mutations within pre-specified genes linked to cardiac conduction system disease. Putative culprit mutations were identified in 3 of 6 cases, including 2 in
SCN5A
(Ala1905Gly [novel] and c.4719C>T [splice site mutation]) and 1 in
LMNA
(Leu327Val [novel]). Biophysical analysis of mutant Ala1905Gly Na
v
1.5 channels in tsA201 cells revealed significantly reduced peak current density and positive shifts in the voltage-dependence of activation consistent with a loss-of-function. The
SCN5A
c.4719C>T splice-site mutation has previously been reported as disease causing in 3 cases of Brugada syndrome, while the novel
LMNA
Leu327Val mutation was associated with a classic laminopathy phenotype. Following catheter ablation, BBRVT was non-inducible in all cases and no clinical recurrences were observed during follow-up.

Conclusions:
Our investigation into apparent idiopathic BBRVT has identified the first genetic culprits for this life-threatening ventricular arrhythmia. This provides further insight into its underlying pathophysiology and emphasizes that conduction system disease, in the absence of ventricular dilation, serves as a sufficient substrate for BBRVT. Our findings also highlight BBRVT as a novel genetic etiology of unexplained sudden cardiac death that can be cured with catheter ablation.
Abstract 12442: Exception to Consent in Pediatric Resuscitation Research: Exploring the Experiences of Substitute Decision Makers
Authors: Parker Melissa J , de Laat Sonya , Schwartz Lisa
Published: April 2024

Introduction:
International research ethics standards endorse an exception to prospective informed consent for research in medical emergencies. While an exception to consent may be ethically justifiable to facilitate rigorous evaluation of time-sensitive interventions in acute life-threatening conditions, little information is available regarding the experiences of participants and substitute decision-makers (SDM). We sought to better understand the experiences of parents/guardians with an exception to consent process as implemented in a pilot RCT involving children with septic shock.

Hypothesis:
Use of an exception to consent process is acceptable to most SDMs.

Methods:
Design:
qualitative research study.
Participants:
SDMs for children enrolled into the SQUEEZE pilot trial [NCT01973907].
Sample size:
Up to 25 participants.
Qualitative Methods:
SDMs are invited to participate in the qualitative ethics study. Interviews with consenting SDMs are conducted in person or by telephone, taped and professionally transcribed. Participants are encouraged to elaborate on their experience of being asked to consent after the fact and how this process occurred.
Analysis:
Data gathering and analysis are undertaken simultaneously with qualitative data coded using NVivo.
Outcome:
Themes emerging from the data.

Results:
Interviews with 15 SDMs, including bereaved and non-bereaved parents/guardians, have been conducted to date. Preliminary findings: 1) SDMs recognized the need for use of an exception to consent process for research in individual medical emergencies; 2) Most SDMs viewed their child’s research participation positively, with many making altruistic statements about helping other children in the future; 3) Perceptions regarding the appropriateness of the timing of the consent approach following enrolment were variable, with some SDMs stating that it was the “right amount of information at the right time", while others felt that they had been approached too soon.

Conclusions:
Substitute decision makers, including bereaved parents/guardians, support use of an exception to consent process in research in individual medical emergencies.
Abstract 12454: Vildagliptin Attenuates Cardiac Hypertrophy and Improves Ventricular Efficiency Through FGF21 Expression in Pressure-overloaded Mouse Heart
Authors: Furukawa Nozomi , Koitabashi Norimichi , Sunaga Hiroaki , Obokata Masaru , Umbarawan Yogi , Syamsunarno Mas R , Yamaguchi Aiko , Matsui Hiroki , Yokoyama Tomoyuki , Kurabayashi Masahiko
Published: April 2024

Introduction:
Basic and clinical studies have shown that Dipeptidyl Peptidase-4 (DPP-4) inhibitor an anti-hyperglycemic agent, has cardioprotective effects through angiogenesis, anti-hypertrophy or anti-apoptosis effect. However, recent clinical trials in patients with diabetes raise a concern about DPP-4 inhibitor’s effect on heart failure. Based on the controversy, we performed precise analyses for cardiac energy metabolism and cardiac performance in hypertrophied heart induced by pressure-overload mouse model with or without diabetes.

Methods and Results:
Non-diabetic C57Bl6 mice (BL6) and type2 diabetic C57Bl6 mice produced by high fat diet (diet-induced obesity, DIO) were treated with or without a DPP-4 inhibitor, vildagliptin (VLD) after inducing pathological cardiac hypertrophy by transverse aortic constriction (TAC). After 3-week treatment, VLD attenuated cardiac hypertrophy and dysfunction compared with vehicle (Veh) treated animals in BL6. However these effects were not observed in DIO mice. Myocardial energy substrate assay using
12
C-FDG (glucose tracer) and
132
I-BMIPP (free fatty acid tracer) showed that not only glucose uptake but also free fatty acid uptake were increased with VLD treatment in TAC heart. Gene expression analysis showed that fibroblast growth factor (FGF) 21, a protein which has been shown to have a critical role in energy metabolism, was increased in heart with VLD treatment.
In vitro
experiments showed that VLD administration increased FGF21 expression dose-dependently in cultured human cardiac fibroblasts but not in neonatal cardiomyocytes, suggesting that fibroblast-mediated FGF21 expression may regulate energy metabolism in stressed heart.

Conclusions:
VLD has a beneficial effect on myocardial energy metabolism associating with an improvement of ventricular performance in hypertrophied heart, partially through upregulation of FGF21. However, these beneficial effects in heart may be attenuated under type2 diabetic condition.
Abstract 12462: Improved Treatment Satisfaction Independent of Stroke and Bleeding Risk Among Patients Transitioned From a Vitamin K Antagonist to Rivaroxaban: A XANTUS-ACTS Analysis
Authors: Coleman Craig I , Haas Sylvia , Turpie Alexander G.G , Kuhls Silvia , Hess Susanne , Evers Thomas , Amarenco Pierre , Kirchhof Paulus , Camm A. John
Published: April 2024

Introduction:
The effectiveness, safety and ease of use of rivaroxaban may reduce anticoagulation treatment burden and improve nonvalvular atrial fibrillation (NVAF) patient satisfaction compared to vitamin K antagonists (VKAs).

Objective:
To assess consistency in changes in treatment satisfaction among patients transitioned from a VKA to rivaroxaban in routine practice across stroke and bleeding risk subgroups.

Methods:
Xarelto on Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation (XANTUS) was a prospective, non-interventional study in patients prescribed rivaroxaban for prevention of stroke in routine practice within 7 European countries and Canada. Patients receiving a VKA 4-weeks prior to the initial XANTUS study visit and switched to rivaroxaban were asked to complete the Anti-Clot Treatment Scale (ACTS). Changes in scores, as recorded during the initial and first follow-up visit at ~3-months (corresponding to a comparison of rivaroxaban vs. prior VKA) for the ACTS Burdens and Benefits scores, were calculated and reported as least squares (LS)-mean differences with standard errors.

Results:
After ~3-months’ rivaroxaban treatment, both Burdens and Benefits scores were significantly improved in NVAF patients with prior VKA treatment (
Table
). Improvements in Burden scores across subgroups were generally consistent (LS-mean difference range, 2.68 to 3.46) with the overall cohort findings. The Benefit score improved in the overall cohort, but was not found to significantly differ in any subgroup (LS-mean difference range, -0.26 to 0.58).

Conclusions:
In XANTUS, patients switching from a VKA to rivaroxaban for stroke prevention reported significant improvements in treatment satisfaction. Independent of stroke or bleeding risk, switching to rivaroxaban appears to improve patient treatment satisfaction; mainly due to a perceived lower treatment burden
Abstract 12474: Nicotinamide Restores Tissue Nad
+
and Improves Outcomes in a Murine Model of Cardiac Arrest
Authors: Zhu Xiangdong , Li Jing , Wang Huashan , Lee Chunpei , Vanden Hoek Terry
Published: April 2024

Introduction:
Metabolic suppression in the ischemic heart is characterized by reduced levels of NAD
+
and ATP.

Hypothesis:
Since NAD
+
is required for most metabolic processes that generate ATP, we hypothesized that nicotinamide (NAM) restore of tissue NAD
+
and improve cardiac function and survival in a mouse model of cardiac arrest.

Methods:
Cardiomyocytes isolated from 1-2-day old C57BL6 mice were exposed to 30 min ischemia and 90 min reperfusion. Contraction recovery was measured by phase contrast imaging without and with 0.1mM NAM given at reperfusion. Adult C57BL6 mice were subjected to an established KCL-induced 8 min cardiac arrest protocol, randomly assigned to receive saline or 500 mg/kg NAM after cardiopulmonary resuscitation (CPR). Survival, MAP, ETCO
2,
and continuous ECG were recorded until 4 h after successful CPR.

Results:
We first tested the effect of NAM on NAD
+
recovery in heart cells exposed to the simulated ischemia and reperfusion. NAD
+
content was decreased from 4.51 ± 0.03 nMol/g before ischemia (equilibration) to 2.69 ± 0.42 nMol/g at the end of ischemia. Treatment with 0.01 mM NAM completely restored the cellular level of NAD
+
by 15 min reperfusion (4.63 ± 0.45 nMol/g), while there was no significant recovery of NAD
+
in untreated cells. This rescue of NAD
+
depletion was associated with improved contractile recovery by 10 min reperfusion (58.1 ± 7.3% return of baseline contractile velocity vs.18.5 ± 3.7% in control cells, n=5,
p
<0.05) that could be augmented further using isoproterenol treatment (83.3 ± 3.5% vs. 58.0 ± 2.9% in control cells.
p
<0.05). We then tested the effect of NAM (500 mg/kg) on mouse SCA 4 h survival and cardiovascular recovery. NAM administered IV after CPR resulted in a trend toward improved mouse SCA survival, with 9/10 survival at 4 h as compared to 5/10 in the saline (NS) group. Compared to saline treated mice, NAM-treated mice displayed improved NAD
+
content in hearts obtained at 4 h post-ROSC compared to saline treated SCA hearts (2.4 ± 0.1 nMol/g vs. 4.5 ± 0.1 nMol/g,
p
<0.05).

Conclusions:
NAM is CPR medication that can rapidly restore cardiac tissue NAD
+
and promote contractile recovery, with improved early survival demonstrated in a mouse model of cardiac arrest.
Abstract 12483: Perceived CVD and Type 2 Diabetes Risk and Knowledge is Low Among Well-Educated Chinese Mothers
Authors: Howie Esquivel Jill , Guo Jia , Chen Jyu-Lin
Published: April 2024

Introduction:
Non-communicable diseases (NCDs) such as CVD and type 2 diabetes (T2D) account for up to 80% of deaths in China. An intervention that reduces CVD and T2D risk in early motherhood could have great impact on the health of Chinese. However, little is known about mothers’ perception of risk for both CVD and T2D. Therefore, we aimed to identify knowledge level and perceived CVD and T2D risk among Chinese women with young children.

Methods:
A cross-sectional study design was used to recruit mothers with children aged 3-5 years in 2 preschools in Hunan Province. Validated questionnaires and measures for Chinese populations were completed to assess: Child feeding practice, family eating and physical activity habits, body weight, waist circumference, parental risk perception for diabetes, and CVD risk survey. Multivariate regression was used to determine variables that independently predicted higher perceived risk.

Results:
Mothers’ (N=196) were mean age 31.0 ±4.3, mean BMI 19.9 ± 3.9, and highly educated as 54% (n=106) had completed college/graduate education. Just 7.3% were overweight/obese (n=14), but 37% (n=73) had waist circumference >80cm. Using the CVD risk survey, 37% (n=73) and 45% (n=88) of mothers reported no perceived risk for coronary heart disease or hypertension, respectively. The parental risk perception for diabetes survey demonstrated low T2D knowledge scores (4.1, range 0-11), 55% (n=107) perceived no risk for developing T2D, and 14% (n=27) reported moderate/high risk for T2D. Predictors associated with increased perceived risk for CVD or T2DM included: Worry about developing T2D (p = .0001) and having blood-related relatives diagnosed with CVD or T2D (p = .003, p = .024 respectively).

Conclusions:
This is the first known study of perceived CVD and T2D risk in early motherhood in China. Despite highly educated participants, more than one-third perceived no risk for heart disease, almost half no risk for hypertension and more than one-half no risk for T2D, although the vast majority of Chinese will die from NCDs such as CVD and T2D. Having blood relatives increases perceived risk of NCDs but it is speculated that education for young mothers regarding their risk and preventive behaviors would improve CVD outcomes.
Abstract 12532: The Tandem Zinc Finger mRNA Binding Protein, Tristetraprolin, is a Novel Regulator of Cardiac Fatty Acid Metabolism Through its Effect on PPARa
Authors: Chang Hsiang-Chun , Sato Tatsuya , Sawicki Konrad T , Shang Meng , Chen Chunlei , Ardehali Hossein
Published: April 2024

Introduction:
Altered substrate utilization has been described in type II diabetes and heart failure (HF), but current therapies do not target the metabolic derangements in these disorders. Identification of novel pathways regulating cellular metabolism could facilitate the development of new therapies. Tristetraprolin (TTP) is a tandem zinc finger protein that binds to AU-rich regions in the 3’ untranslated region (UTR) of mRNA molecules and causes their degradation. Its expression is reduced in patients with diabetes, and its cellular level is regulated by mTOR, a key protein involved in cellular metabolism. Furthermore, the yeast homolog of TTP has been suggested to play a role in metabolism. Thus, we hypothesized that TTP regulates cardiac metabolism and plays a role in the development of HF through its effects on substrate utilization in the heart.

Results:
We first assessed the effects of TTP modulation on cellular substrate utilization, and found that TTP downregulation in cultured cardiomyocytes resulted in higher palmitate uptake and oxidation while its overexpression had the opposite effect. Since TTP regulates its targets at the mRNA level, we studied the mRNA levels of all genes involved in lipid metabolism, and found that only PPARα mRNA to be significantly increased with TTP downregulation. Furthermore, we demonstrated that TTP physically interacts with PPARα mRNA, and the activity of a luciferase reporter harboring full-length PPARα 3’UTR is increased with TTP downregulation. Additionally, PPARα mRNA is stabilized with TTP knockdown. We then studied the role of TTP in cardiac metabolism using mice with cardiac-specific TTP knockout. Although cardiac-specific TTP knockout mice had normal cardiac function at baseline, they displayed higher fatty acid utilization compared to wild type littermate control in an ex vivo heart perfusion setup. We also demonstrated a significantly higher TTP levels in failing human and mouse cardiac samples, suggesting that TTP levels are altered in HF.

Conclusion:
Our results demonstrate that TTP is a novel regulator of cardiac fatty acid metabolism through its effect on PPARα, and that its levels are increased in HF. Thus, modulation of TTP may be a viable therapeutic approach for HF.
Abstract 12551: Manifestation of J Waves in the General Population is Associated With Excessive Trabeculation Localized in the Left Ventricular Apex
Authors: Kaneko Yoshiaki , Kurosawa Koji , Nakajima Tadashi , Irie Tadanobu , Iizuka Takashi , Kurabayashi Masahiko
Published: April 2024

Introduction:
The presence of J wave in inferior and lateral ECG leads is a common finding in the general population, but the electrophysiological mechanism underlying the manifestation of the J wave remains unclear. Left ventricular (LV) trabeculation is frequently observed in healthy individuals, but its extent is highly variable among individuals.

Hypothesis:
Excessive LV trabeculation (ELVT) may be a cause of J wave in the general population.

Methods:
Of outpatients in our hospital for last 5 years who underwent 12-lead ECG and transthoracic echocardiography (TTE) simultaneously, we identified 148 patients who satisfied the following criteria: (1) no abnormalities on 12-lead ECG, (2) fair visualization of TTE especially in a short-axial view at the papillary muscle and an apical level, respectively, and in a long-axial apical view, and (3) no previous history of nor no echocardiographic evidence of heart diseases. We searched for ELVT, semi-quantitatively defined as the presence of noncompaction greater compaction. The study population was divided into 56 patients with J waves (56±17 year-old, 44 men. J-wave group), characterized by ≥0.1 mV notches or slurs of the terminal portion of the QRS complex, and 92 patients without (59±15 year-old, 39 men, control).

Results:
There was no significant difference in ECG parameters including RR, PQ, QRS width, QT and QTc between the two groups. In J-wave group, J wave with 0.2±0.1 mV, ranging between 0.1 and 0.5, was observed in the inferior leads in 51 patients, left precordial in 30 and high lateral in 10, and its morphology was slur in 36, notch in 11 and both in 9. ELVT was observed more frequently in J-wave group than control (28 patients (50%) versus 15 (16%), p<0.01), but was distributed mainly in inferolateral wall of LV apex in both groups (inferior in 15 patients, lateral in 24, 1 in anterior and 1 in septal versus inferior in 1 and lateral in 15, p=0.04). No ELVT was detected at the papillary muscle level in both groups.

Conclusions:
These observations support our hypothesis that ELVT localized in the LV apex, probably carrying the Purkinje system deeper into the midmyocardium, might alter a propagation process in the terminal portion of QRS complexes, thus resulting in the manifestation of J waves in the general population.
Abstract 12554: Circulating Eosinophil Count is Associated With Thoracic Aortic Wall Thickness Evaluated by Computed Tomography
Authors: Takeda Yoshihiro , Fujita Shu-ichi , Morita Hideaki , Sohmiya Koichi , Hoshiga Masaaki , Ishizaka Nobukazu
Published: April 2024

Background and Purpose:
Eosinophil count is known to be increased in various forms of arteritis/aortitis that may potentially lead to vascular wall thickening. We investigated whether circulating eosinophil count is associated with aortic wall thickness.

Methods:
Subjects who underwent 320 detector-row computer tomography (Toshiba Medical Systems, Tokyo, Japan) to evaluate the coronary artery were enrolled in the study. Aortic wall thickness was measured perpendicularly to the center of the aorta in the axial image. The protruding atheroma was defined as the maximum aortic wall thickness of ≥4 mm with irregular surface.

Results:
This study included 405 patients (255 men) with mean age 67.6 +/- 10.5 years old. Those patients with aortic wall thickness of ≤2 mm (n=109), 2-2.9 mm (n=179), 3-3.9 mm (n=70), and ≥4 mm (n=47) had eosinophil count (cells/μL) of 120.0, 130.3, 133.2 and 222.4, respectively. Eosinophil count was positively associated with aortic wall thickness (R
2
=0.034, P<0.001), meanwhile, neutrophil, monocyte, basophil and lymphocyte count were not. By multiple regression analysis using eosinophil count and other potential confounders including sex, age, BMI, systolic blood pressure, lipid and glucose profile, and renal function as independent variables, eosinophil count was selected as a factor that had significant association with aortic wall thickness with correlation coefficient of 0.172 (95% confidence interval 0.001-0.003, p<0.0001). In addition, multiple logistic regression analysis using eosinophil count tertile and other atherosclerotic risk factors as independent variables showed that the 2
nd
and 3
rd
eosinophil count tertile were independently associated with protruding atheroma with an odds ratio of 2.82 (95% confidence interval 1.16-6.80, P=0.022) and 5.75 (95% confidence interval 1.79-18.52, P=0.003).

Conclusions:
Eosinophil count was associated with thoracic aortic wall thickness. Considering that circulating eosinophil is increased in various immuno-inflammatory aortic disease, histopathologic analyses should be performed to investigate whether there is any causal and resultant relationship underlying this observed link between eosinophil and aortic wall thickening.
Abstract 12579: Sirt2 Contributes to the Development of Heart Failure Through a Nrf2 Dependent Pathway
Authors: Yang Xiaoyan , Shang Meng , Kamide Christine Elizabeth , Chen Chunlei , Park Seong-Hoon , Wu Rongxue , Liu Ting , Vassilopoulos Athanassios , Ardehali Hossein
Published: April 2024

Introduction:
Heart failure is associated with a change in cardiac energy metabolism and increased oxidative stress. Sirtuins (SIRTs) are NAD+-dependent deacetylases, and critical regulators of energy metabolism and oxidative stress response. However, the function of SIRT2, the only cytosolic sirtuin protein, in regulating the development of heart failure is largely unknown.

Methods and results:
To explore the role of SIRT2 in the development of heart failure, we examined the response of
Sirt2
-/-
mice and their littermate controls to pressure overload by transverse aortic constriction (TAC) and cardiac ischemia/reperfusion (I/R).
Sirt2
-/-
mice had normal appearance and cardiovascular parameters at baseline. However, in response to TAC,
Sirt2
-/-
mice displayed resistance to the pathological hypertrophic response. In the I/R injury model,
Sirt2
-/-
mice had better cardiac function and less cardiac fibrosis after 28 days of surgeries compared to WT mice.
In vitro
,
Sirt2
knockdown reduced reactive oxygen species (ROS) production and cell death in neonatal rat cardiomyocytes (NRCM) after H
2
O
2
treatment. Since cellular oxidative stress is a key contributing factor to both I/R and cardiac hypertrophy, and nuclear factor (erythroid-derived 2)-like 2 (NRF2) plays a major role in antioxidant activity of the cell through regulation of several antioxidant proteins, we tested whether NRF2 is involved in SIRT2-mediated cardiac response to oxidative stress. We found that NRF2 expression is higher in NRCM with
Sirt2
knockdown compared to WT cells after H
2
O
2
stimulation. And NRF2 is translocated into the nucleus and its anti-oxidant target proteins are upregulated in NRCM with
Sirt2
knockdown. Further experiments demonstrated that SIRT2 directly interacts with and deacetylates NRF2, and reduces its nuclear translocation and transcriptional activity. In addition,
Sirt2
-/-
mice have higher levels of acetylated NRF2 in the heart. Finally, knockdown of both
Sirt2
and
Nrf2
abrogates the effects of
Sirt2
knockdown on ROS production and cellular damage.

Conclusion:
Our results indicate that SIRT2 contributes to the development of heart failure in mice, and promotes oxidative stress injury in cardiomyocytes by deacetylating NRF2 and altering its activity.
Abstract 12591: Preservation of Cardiac Structure and Function Compared to Brain in a Rat Hemorrhagic Shock Model
Authors: Dai Wangde , Kloner Robert A
Published: April 2024

Background:
Hemorrhagic shock (HS) and resuscitation were hypothesized to induce myocardial injury and/or stunned myocardium. In this study we assessed cardiac function during HS and resuscitation in rats.

Methods:
Pressure-controlled HS was induced by blood shedding (withdrawal at 0.5 ml/min) in rats (n=5). Mean arterial blood pressure (MBP) was maintained at 29 ± 1 mmHg for 2 hours, followed by resuscitation with the shed blood. At 3 hours after resuscitation, saline was infused at 0.5 ml/min (2.5 ml) to assess cardiac and vascular reactivity. Cardiac function was continuously monitored by transthoracic echocardiogram during the procedure. Brain, heart, liver and kidney were sliced and stained with triphenyltetrazolium chloride for necrosis assessment.

Results:
No rat died during the procedure. Heart rate, MBP, diastolic and systolic left ventricular (LV) diameter, and LV fractional shortening (LVFS) were reported at 6 time points in the table: 1) baseline prior to HS; 2) beginning of HS; 3) end of the HS; 4) post-resuscitation peak MBP; 5) end of 3 hours of post-resuscitation; 6) 5 minutes after saline infusion at 0.5 ml/min. Heart rate significantly decreased during blood shedding (p < 0.05), then significantly increased during HS (p < 0.05). MBP significantly fell during HS (P < 0.05) and then recovered to baseline level after reinfusion of shed blood; it significantly dropped (compared to baseline) at 3 hours after resuscitation (p < 0.05). Saline infusion rapidly recovered MBP, LV diastolic diameter and LVFS to baseline level, which suggested that cardiac and vascular reactivity to fluid resuscitation were preserved during HS and post-resuscitation. LVFS remained preserved throughout the study; shock did not cause stunned myocardium. There were infarcts in 5 brains; no necrosis was detected in hearts, kidneys or livers.

Conclusions:
Cardiac function was preserved during HS and resuscitation with no evidence of stunning or infarction, while strokes were common.
Abstract 12647: Linagliptin Reduces Arterial Stiffness and Arterial Inflammation in Persons With Early Type 2 Diabetes: a Double-blind, Randomized Controlled Trial
Authors: de Boer Stefanie A , Heerspink Hiddo J , Lefrandt Joop D , van Roon Arie M , Juàrez Orozco Luis E , Glaudemans Andor W , Kamphuisen Pieter W , Slart Riemer H , Mulder Douwe J
Published: April 2024

Introduction:
Dipeptidyl peptidase (DPP)-4 inhibitors are a class of oral antidiabetic drugs. Recent experimental studies have suggested beneficial vascular effects, but clinical evidence is limited.

Hypothesis:
The primary objective was to evaluate the effects of the DPP-4 inhibitor linagliptin on aortic pulse wave velocity (PWV) as a measure of arterial stiffness and secondarily, on arterial
18
F-fluorodeoxyglucose (FDG) positron emission tomography (PET) uptake as a measure of arterial inflammation in type 2 diabetes.

Methods:
A total of 45 treatment naive type 2 diabetes patients (median age 63 (IQR 54-66) years, 61% male, mean HbA1c 6.3±0.4 (%)) without cardiovascular disease were randomized (1:1) to linagliptin 5 mg or placebo for 26 weeks in a double-blind fashion. PWV was assessed at baseline, 4, 26 weeks of treatment and at 30 weeks (washout). Arterial inflammation was quantified by FDG uptake as the pre-scan glucose corrected maximal standardized uptake value corrected for background (TBR). TBRs were calculated for the carotid arteries, ascending aorta and aortic arch, descending and abdominal aorta, and iliac and femoral arteries, and averaged for the total aortic tree (
mean
TBR).

Results:
PWV decreased in the linagliptin group and was stable placebo (Figure A). The generalized linear model analysis showed a mean group difference of linagliptin compared to placebo of 0.91 m/s [95% CI 0.06-1.76](p=0.035) at 26 weeks. PWV returned to baseline after washout.
mean
TBR decreased in the linagliptin group compared with placebo by 0.18 [0.04-0.32] (p=0.015) after 26 weeks (Figure B). Linagliptin compared with placebo decreased HbA1c (p<0.001), fasting plasma glucose (p=0.002), and triglycerides (p=0.019).

Conclusions:
Linagliptin reduces aortic PWV as a measure of arterial stiffness and arterial FDG uptake as a measure of arterial inflammation compared with placebo after 26 weeks of treatment in early type 2 diabetes patients.
Abstract 12656: Decreased Kidney Function in the Form of Estimated Glomerular Filtration Rate Increases the Risk of Development of Incident Hospitalized Heart Failure and Its Subtypes in Post-menopausal Women
Authors: Ashraf Farhan , Barbour Mohamad F , Abdin Ahmad , Roberts Mary B , Eaton Charles B
Published: April 2024

Introduction:
While coronary heart disease is decreasing in prevalence, Heart Failure (HF) is increasing in prevalence. Effective treatment is known for Heart Failure with reduced ejection fraction (HFrEF), but there is no effective treatment for Heart Failure with preserved ejection fraction ( HFpEF). Post-menopausal women have high rates of HFpEF and the association with decreased kidney function is under-researched in this high risk group.

Hypothesis and Objectives:
Decreased kidney function measured as estimate glomerular filtration rate (eGFR) increases the risk of development of HF and HFpEF.

Methods:
Study participants are postmenopausal women (n=23,128) who had their serum creatinine levels measured, and who are free of Heart Failure at baseline, evaluated in the Women Health Initiative (WHI). eGFR was calculated using Chronic Kidney Disease-Epidemiology Collaboration equation. The association between eGFR and incident HF, HFpEF and HFrEF was evaluated using Cox proportional hazards models. eGFR was analyzed as a categorical exposure and test for trend were performed.

Results:
Among the 23,128 women in this study, 1486 developed HF over 272,323 person-years of follow-up. Decreased kidney function in the form of decreased eGFR was associated with increased risk of development of total HF and HFpEF. This risk was strongest in the eGFR <45 ml/min/ 1.73 m
2
(see table).

Conclusion:
Decreased kidney function was associated with increased risk of development of total HF and HFpEF in post-menopausal women in a dose-response manner but was only significant at eGFR < 45 ml/min/ 1.73 m
2
for HFrEF. This association is much stronger for HFpEF compared to HFrEF at this cut-point.
Abstract 12659: Relationship Between Cardiac Structure and Function With Neurocognition in the Hispanic Community Health Study/ Study of Latinos (HCHS/SOL) Echocardiographic Study of Latinos (Echo-SOL) Ancillary Study
Authors: Almahmoud Mohamed Faher , Gonzalez Hector M , Tarraf Wassim , Schneiderman Neil , Kansal Mayank M , Lamar Melissa , Talavera Gregory A , Rodriguez Carlos J
Published: April 2024

Background:
Neurocognitive impairment is an important challenge facing the growing elderly population. The heart’s effect on the brain with regard to neurocognition is less well-studied. We evaluated the association between cardiac structure and function with neurocognition measurements in a population-based cohort.

Methods:
The Echo-SOL Ancillary Study of Hispanic adults aged 45-74 years provided comprehensive neurocognitive and echocardiography assessments for cross-sectional analysis. Neurocognitive measures included the Word Fluency (WF) Test, the Brief-Spanish English Verbal Learning Test (SEVLT), and the Digit Symbol Substitution Test (DSST); lower WF, SEVLT, and DSST scores signifying worse neurocognitive function. Multivariable linear and logistic regression models were fit using survey statistics and accounted for sampling probabilities, age, sex, diabetes, hypertension, and BMI.

Results:
1818 participants were included in the analysis: mean age 56-years, and 56% women. Higher left ventricular mass index was associated with lower SEVLT and DSST scores, whereas lower Ejection Fraction and lower peak systolic velocity were associated with lower WF scores. Lower SEVLT scores were seen with a higher prevalence of abnormal left ventricular geometry and higher relative wall thickness. Mitral annular relaxation velocities (e’) were significantly associated with lower SEVLT and WF scores. Additionally, a higher ratio of mitral inflow velocity with mitral annular early diastolic velocity (E/e’) and more prevalent left ventricular diastolic dysfunction were significantly associated with lower SEVLT scores.

Conclusion:
Abnormalities in cardiac structure and function are associated with alterations in neurocognitive function in Hispanics/Latinos. Further study is needed to determine the mechanisms (e.g., impairment of cerebral flow, silent brain infarctions) mediating these potentially important heart-brain associations.