bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12657: Perceptions of the Role of Community Health Workers in Hypertension Management: A Qualitative Analysis of the LARK Hypertension Study
Authors: Bakshi Salina , Naanyu Violet , Kamano Jemima H , Rotich Jackson K , Kiptoo Peninah , Lagat Kennedy K , Kofler Claire , Menya Diana , Kimaiyo Sylvester , Inui Thomas S , Horowitz Carol R , Fuster Valentin , Vedanthan Rajesh
Published: April 2024

Background:
Hypertension, a major risk factor for cardiovascular disease, is the leading risk factor for global mortality. Increasing access to hypertension care is critically important to reducing the burden of global cardiovascular disease. The use of community health workers (CHWs) to increase access to care represents a potential strategy to improve hypertension treatment and control; however, it is not known how rural communities in low- and middle-income countries perceive the use of CHWs for this purpose. Our study therefore aims to examine community perceptions of CHWs in hypertension management.

Methods:
Traditional community gatherings and focus group discussions (20 sessions, 411 participants) were organized in rural western Kenya. Discussion topics included chronic diseases, factors related to linkage to care, and the role of CHWs in hypertension management. We performed inductive content analysis of transcripts from these sessions using NVivo 10 software. Coded items were grouped together into distinct themes, and relationships among these themes were formulated.

Results:
Six themes emerged from our analysis, each with implications regarding CHWs’ role in linkage and retention to hypertension care (Table). These themes included (1) CHWs’ intimate knowledge of the community; (2) CHWs’ role in providing health education; (3) CHWs’ role in facilitating logistical support to enable community members to access care; (4) the importance of psychosocial support that CHWs can provide; (5) the need for ‘professionalization’ of the CHW workforce; and (6) negative perceptions towards CHWs.

Conclusions:
Our themes are consistent with findings in the literature regarding the work that CHWs traditionally perform for communicable diseases and maternal/child health. Use of CHWs for hypertension management, leveraging the prior experience of other CHW programs, may be an effective strategy to reduce the burden of hypertension in low-resource settings.
Abstract 12674: Left Ventricular Myocardial Strain Gradient on a Novel Multi-layer Transthoracic Echocardiography Technique Positively Correlated With Degree of Severe Aortic Stenosis
Authors: Ozawa Koya , Funabashi Nobusada , Takaoka Hiroyuki , Kobayashi Yoshio
Published: April 2024

Introduction:
A recently developed transthoracic echocardiography (TTE) technique enables detailed myocardial multi-layer analysis of left ventricular (LV) endocardial, epicardial and whole transmural layer strain.

Hypothesis:
Myocardial strain gradient, defined as endocardial/epicardial strain may influence aortic stenosis (AS) severity. To probe the mechanism behind AS severity we measured myocardial strain gradients in severe AS subjects with preserved LV ejection fraction (LVEF) using a novel, multi-layer speckle tracking TTE technique.

Methods:
36 severe AS subjects (19 male, 77±7 years, LVEF >50%, transaortic maximum velocity 4.8±0.6m/s, aortic valve area index (AVAI) 0.45±0.11 cm2/m2) underwent TTE (Vivid E9, GE Healthcare). Apical 4-, 2-, and 3-chamber GLS views and parasternal short axis GCS views at the level of the mitral valve, papillary muscle, and apex were acquired. GLS was defined as all 17 averaged LV segments. GCS was defined as averaged LV segments at the level of the mitral valve, papillary muscle, and apex, respectively. Furthermore strain measurements of whole, endocardial, and epicardial layers were performed. Myocardial strain gradient was defined as: endocardial/epicardial strain.

Results:
Absolute value of averaged endocardial layer 2D LV GLS was significantly greater than that in the epicardial layer (P<0.001). Absolute values of endocardial layer GCS at all levels were significantly greater than those of the epicardial layer(all P<0.001). The GLS, but not the GCS at any levels, gradient significantly positively correlated with transaortic maximum velocity (R=0.404, P=0.015) and negatively correlated with AVAI (R=-0.463 P=0.005).

Conclusions:
In severe AS subjects with preserved LVEF, the LV GLS gradient positively correlated with transaortic maximum velocity and negatively correlated with AVAI. Therefore GLS gradients may influence AS severity.
Abstract 12762: Cardiac Hypertrophy is Associated With Discordant Protein Turnover in Metabolic Pathways
Authors: Lau Edward , Cao Quan , Ng Dominic , Wang Ding , Lam Maggie P , Ping Peipei
Published: April 2024

Introduction:
Cardiac hypertrophy preceding heart failure is commonly associated with disrupted protein homeostasis. How alterations in protein temporal stability and turnover may contribute to disease phenotypes is poorly understood, due in part to difficulties in measuring protein half-life in the heart in vivo.

Hypothesis:
We hypothesize that disrupted proteostasis contributes to cardiac remodelling in part by altering the turnover rates of enzymes necessary to maintain cardiac functions.

Method:
We developed a technology platform combining stable isotope mass spectrometry, computational modelling and a systems genetics model to investigate the dynamics of proteome remodelling in cardiac hypertrophy over six inbred mouse strains. The mice (C57BL/6J, DBA/2J, CE/J, A/J, FVB/NJ, BALB/cJ) were selected from a panel of >100 strains for their contrasting responses to isoproterenol, which permits regression modelling of proteome dynamics over phenotypic responses.

Results:
We completed 1,404 LC-MS/MS experiments to quantify the turnover and abundance of 3,227 proteins from 127,648 data series. We performed weighted correlation network analysis to classify the protein data into 15 modules in an unsupervised manner. Strikingly, we found that protein interaction partners and functionally related proteins share synchronous turnover, and that coordinated turnover networks overlapped with metabolic pathways. Regression models show the turnover rate of glycolytic enzymes is a positive predictor of the severity of cardiac hypertrophy in the mouse strains (r: 0.58 - 0.80), whereas the turnover of fatty acid oxidation proteins (e.g., ACAT1, ACAD10, HADHA/B, DBT, ACAA2) is negatively correlated (r: -0.66 - -0.89).

Conclusion:
Our study provides the first clues on the association between cardiac remodelling and protein turnover networks, and uncovered potential disease drivers that evade steady-state gene expression analysis.
Abstract 12886: The Relationships Among Sleep Apnea, Brain Volumes, and Cognition in Individuals With Heart Failure
Authors: Moon Chooza , Melah Kelsey , Johnson Sterling C , Bratzke Lisa C
Published: April 2024

Introduction:
Approximately 25% to 75% of heart failure (HF) patients have sleep apnea (SA), which may contribute to brain changes that are associated with decreases in attention, memory, and executive function. Unfortunately, there is a dearth of research that explores how SA may contribute to brain changes and cognition within the HF population. Thus, the purpose of this study is to examine the relationships between the apnea-hypopnea index (AHI), grey and white matter brain volumes, and neuropsychological test scores of attention, memory and executive function.

Hypothesis:
HF patients with higher AHI would have decreased brain volumes and neuropsychological test scores.

Methods:
Using a cross-sectional design, we sampled 28 HF patients; 13 HF patients had AHI ≥ 10 and 15 HF patients had AHI <10. Eighty percent were male (n=12) and their mean age was 68 (SD = 5). We evaluated AHI with a portable multichannel sleep-monitoring device, brain volumes with voxel-based morphometry method T-1 weighted images from 3.0 T magnetic resonance imaging, and cognition with a neuropsychological test battery. We used multiple regression analysis to examine proposed relationships. For analysis of AHI and brain volumes, we controlled for age, sex, education, left ventricular ejection fraction , and intracranial volume.

Results:
In regression models adjusting for covariates, AHI was significantly related to reduced grey matter volume in areas including the inferior temporal gyrus, fusiform gyrus, cingulate gyrus, and superior frontal gyrus (p <0.001). In white matter volume, AHI was related inversely to white matter volume in areas such as superior temporal gyrus and superior frontal gyrus (p<0.001). However, AHI was not correlated with any of the neuropsychological test scores.

Conclusion:
AHI was associated with reduced grey and white matter volumes in the brain. These are areas associated attention and memory. However, AHI was not related to any of the cognitive test scores. In dementia literature it has been shown that brain changes precede changes in cognition by months to years. Therefore, longitudinal, prospective studies are recommended to determine whether brain volume changes that are associated with sleep apnea precede cognitive decline in individuals with HF.
Abstract 12934: The Impact of Peripheral Artery Disease Assessed by Ankle-Brachial Index on Endothelial Dysfunction and Risk of In-Stent Restenosis After Percutaneous Coronary Intervention
Authors: Komura Naohiro , Tsujita Kenichi , Yamanaga Kenshi , Sakamoto Kenji , Iwashita Satomi , Kojima Sunao , Kaikita Koichi , Hokimoto Seiji , Hibi Kiyoshi , Sugano Teruyasu , Kimura Kazuo , Umemura Satoshi , Ogawa Hisao
Published: April 2024

Introduction:
The problem of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) remains unresolved. Patients with peripheral artery disease (PAD), defined as a decreased ankle brachial index (ABI), have high cardiovascular event rates and impaired endothelial function predicts future cardiovascular events. However, to our knowledge, no studies have assessed the relationship among ABI, endothelial dysfunction, and ISR after PCI.

Hypothesis:
We assessed the hypothesis that low ABI at PCI is associated with a high incidence of ISR.

Methods:
ABI and endothelial function were checked before PCI and at follow-up (F/U) angiography in 243 consecutive patients who had successful PCI. Endothelial function was assessed by measuring the reactive hyperemia index (RHI) from fingertip using a RH-PAT device. Patients were categorized according to their ABI values (PAD: ABI≦0.9, borderline: 0.9<ABI50% at F/U angiography assessed by quantitative coronary angiography.

Results:
Within the study population there were 27 PAD, 26 borderline, and 190 normal ABI at the index PCI. Among them, ISR was demonstrated in 68 patients (28%). As the PAD status become worse, patients were found to have significantly higher ISR rate (PAD: 52%, borderline: 35%, normal: 24%, p=0.02) and more impaired peripheral endothelial function assessed by RHI (PAD: 1.49±0.44, borderline: 1.77±0.41, normal: 1.97±0.52, p=0.0001). Furthermore, patients with ISR were found to have significantly lower ABI than those without ISR (1.05±0.15 vs. 1.11±0.13 p=0.004). By multivariate logistic regression analysis even after adjusting for other significant parameters in univariate analysis (BMS use, Calcium antagonist use, MLD post PCI, Total stent length, right coronary artery stenting, current smoking, HDL-Cholesterol, and ACS presentation), PAD proved to be the independent predictor of ISR (Odds ratio 3.32; 95% confidence interval; 1.29 to 8.54, p=0.01).

Conclusions:
In patients undergoing PCI, PAD is independently associated with a higher rate of subsequent ISR. Impaired endothelial dysfunction may contribute to this adverse outcome. These findings have important implications for the careful F/U of PAD patients undergoing PCI as ISR-prone patients.
Abstract 13033: Titin Mutations in IPS Cells Define Sarcomere Insufficiency as a Cause of Dilated Cardiomyopathy
(Best of Basic Science Abstract)
Authors: Hinson J. Travis , Chopra Anant , Swist Sandra , Benson Craig , Sheng Calvin , Nafissi Navid , Polacheck William , Hubner Norbert , Linke Wolfgang , Cook Stuart , Chen Christopher , Seidman Jonathan , Seidman Christine
Published: April 2024

Introduction:
Dilated cardiomyopathy (DCM) is one of the most common cardiovascular disorders with a prevalence of 1:250 patients. Patients with DCM develop left ventricular dilation, systolic dysfunction, and ultimately heart failure. While DCM can occur due to acquired cardiovascular conditions, our group recently identified mutations in the giant sarcomere protein titin (TTN) as the most common genetic cause of DCM, occurring in 15-20% of familial or sporadic cases. Truncation mutations in the A-band of TTN are enriched in DCM cases, while truncation mutations in the I-band are less pathogenic and are commonly found in normal patients. How some mutations in TTN lead to DCM remains unclear.

Hypothesis:
We tested whether myocytes derived from induced pluripotent stem cells (iPS-CMs) with mutations in TTN in the A-band and I-band could recapitulate features of DCM by single myocyte and cardiac microtissue (iPS-CMT) assays.

Methods & Results:
We engineered a panel of patient-specific iPSc’s with two truncation mutations in the A-band and a missense mutation, W976R, in the Z/I junction of TTN. TTN mutant iPS-CMTs had impaired baseline contractility and impaired response to both mechanical and adrenergic stress. In addition, isogenic iPSc lines with TTN truncation mutations in the A- and I-bands also had similarly reduced contractile function. By combining functional analyses with RNAseq, we determine that TTN truncations in the I-band are less pathogenic because I-band exons are spliced out in the adult left ventricle but are expressed in iPS-CMs. Finally, we demonstrate that mutant TTN protein in iPS-CMs leads to sarcomere insufficiency and growth factor and cell signaling deficiencies.

Conclusion:
iPS-CMs and iPS-CMTs with TTN mutations derived from patient-specific and CRISPR/CAS9-edited iPScs recapitulate contractility and adaptation deficiencies often identified in patients with dilated cardiomyopathy. TTN truncation mutations in the A-band may cause DCM by impaired sarcomerogenesis while I-band truncations are spliced out and are tolerated. Sarcomere abnormalities lead to failure to activate growth factor and cell signaling pathways. The iPS-CMT assay can be a powerful strategy to determine the pathogenicity of DCM mutations.
Abstract 13240: Soluble Flt-1 Deficiency is One of the Mechanisms of Cardiac Hypertrophy and Heart Failure in CKD Through Up-regulation of MCP-1
Authors: Seno Ayako , Takeda Yukiji , Matsui Masaru , Nakada Yasuki , Ueda Tomoya , Matsumoto Takaki , Okuda Aya , Jonckx Bart , Nakagawa Hitoshi , Onoue Kenji , Watanabe Makoto , Kawata Hiroyuki , Kawakami Rika , Uemura Shiro , Saito Yoshihiko
Published: April 2024

Background:
Uremic cardiomyopathy is responsible for high morbidity and mortality in patients with chronic kidney disease (CKD), which is characterized by cardiac hypertrophy and heart failure. But precise mechanisms are still unknown. In our previous data, soluble Flt-1 (sFlt-1), which is an endogenous inhibitor of PLGF (placental growth factor), is a key molecule of cardiovascular disease in CKD. Soluble Flt-1 production was decreased with the progression of renal diseases, and sFlt-1 deficiency resulted in progression of cardiac hypertrophy and heart failure, which was revealed by using sFlt-1 KO mice (sFlt-1
-/-
). In this study, we examined the novel mechanisms of heart failure and cardiac hypertrophy using sFlt-1
-/-
mice which mimic the CKD condition.

Methods and Results:
We performed transverse aortic constriction (TAC) in sFlt-1
-/-
and WT, and evaluated after 7 days. LV wall thickening was significantly increased and ejection fraction was decreased in sFlt-1
-/-
compared to WT by echocardiography. Histological analysis showed that myocardial fibrosis and macrophage infiltration were significantly increased in sFlt-1 KO compared to WT. Anti-PLGF neutralizing antibody (αPLGF: ThromboGenics, Heverlee, Belgium) prevented pressure-overloaded cardiac hypertrophy and cardiac dysfunction after TAC in sFlt-1
-/-
. In addition, MCP-1 expression was increased in the hearts of sFlt-1
-/-
compared to WT after TAC. Echocardiographic analysis showed that inhibition of MCP-1 with neutralizing antibody prevented cardiac hypertrophy and systolic dysfunction in sFlt-1
-/-
, which implied that MCP-1 was one of the key chemokines for the progression of heart failure in sFlt-1 deficiency. Human cardiac biopsy samples revealed that macrophage mobilization, fibrosis, and MCP-1 expression were increased in uremic cardiomyopathy, which was quite similar to sFlt-1
-/-
.

Conclusions:
The present study demonstrated that PLGF activation in CKD by decrement of sFlt-1 induced macrophage activation and MCP-1 up-regulation which led to cardiac hypertrophy and heart failure. PLGF and MCP-1 are novel mechanisms and therapeutic target of cardiac hypertrophy and heart failure in CKD.
Abstract 13427: Treatment With a Direct Thrombin Inhibitor Interrupts the Progression of Obesity-Associated Pathologies in Mice Fed a High Fat Diet
(Best of Basic Science Abstract)
Authors: Kopec Anna K , Joshi Nikita , Cline-Fedewa Holly , Williams Kurt J , Nault Rance , Zacharewski Tim R , Goss Ashley , van Ryn Joanne , Luyendyk James P
Published: April 2024

Obesity is accompanied by activation of the coagulation cascade in humans and in experimental settings of diet-induced obesity. Genetic and pharmacologic interference with thrombin proteolytic activity has previously been shown to attenuate obesity-associated pathologies, including non-alcoholic fatty liver disease (NAFLD). In this study we sought to determine if intervention with the thrombin inhibitor, dabigatran etexilate (DE), can slow the progression of NAFLD and obesity when administered after onset of disease. Wild-type C57BL/6J mice were fed a control diet (AIN-93M, 10% calories from soybean oil) or a high fat diet (HFD, 60% calories from lard and soybean oil) for 3 months and then switched to identical diets containing 7.5 mg/g DE (AIN-93M+DE and HFD+DE) for an additional 2 months (intervention groups). Additional groups of mice were fed DE-containing diets for all 5 months (prophylactic groups). Terminal plasma DE levels were comparable (~330 ng/ml) in mice fed AIN-93M+DE and HFD+DE. Therapeutic intervention with DE prevented excess body weight gain, marked by no further increase in body fat mass, in HFD-fed mice. DE treatment elicited a selective reduction in micro-, but not macro-vesicular, hepatocellular steatosis in mice with established HFD-induced obesity. In addition, DE treatment prevented progression of liver injury (i.e., serum alanine aminotransferase levels) in HFD-fed mice. HFD-induced hyperglycemia was significantly attenuated in DE-treated mice, suggesting improved insulin sensitivity. DE treatment did not significantly affect these parameters in AIN-93M-fed mice. Analysis of inflammatory cytokines linked to metabolic inflammation revealed a robust increase in plasma KC/Gro, a neutrophil chemokine related to adiposity and insulin resistance, in HFD-fed mice. Notably, both prophylaxis and intervention with DE dramatically reduced plasma KC/Gro levels. Overall, the data suggest that DE can halt the progression of diet-induced obesity and NAFLD in mice fed a HFD. Moreover, the results suggest that thrombin-mediated chemokine induction contributes to HFD induction of obesity and liver disease in mice.
Abstract 13451: Assessment of Diffuse Ventricular Fibrosis in Atrial Fibrillation Using Extracellular Volume Fraction: Initial Study
Authors: Li Song-Nan , Zhao Lei , Wang Lu , Lin Hui , Wen Song-Nan , Ning Man , Ma Xiao-Hai , Yu Rong-Hui , Long De-Yong , Tang Ri-Bo , Sang Cai-Hua , Jiang Chen-Xi , Liu Nian , Bai Rong , Du Xin , Dong Jian-Zeng , Fan Zhan-Ming , Ma Chang-Sheng
Published: April 2024

Objectives:
In atrial fibrillation (AF), diffuse myocardial fibrosis may be induced by arrhythmia or reflect pre-existing cardiomyopathy. The presence of concurrent AF and diffuse myocardial fibrosis has been associated with an increased risk of heart failure progression.Unlike focal fibrosis, diffuse myocardial fibrosis is not visualized on delayed enhancement magnetic resonance imaging (MRI), but can be quantified with ECV fraction.

Hypothesis:
The extracellular volume (ECV) fraction may provide new insights to evaluate diffuse myocardial fibrosis of the left ventricle (LV) in patients with AF.

Methods:
78 subjects underwent MRI using a clinical 3 T scanner (Magnetom Verio, Siemens Healthcare): 25 persistent AF patients, 28 paroxysmal AF patients and 25 controls. Left-atrial volume was evaluated from MR cine imaging. A validated Look-Locker T1 Mapping Siemens prototype sequence was used to generate T1 maps as an index of diffuse myocardial fibrosis. The imaging parameters were: TE/TR = 1/295.33ms, FOV = 360mm, Slice Thickness = 8mm, image matrix = 192. 3 short axes of pre and post T1 maps were acquired as shown in Figure 1. ECV fraction was calculated from T1 maps acquired pre- and post-contrast calibrated by blood hematocrit. The ECV fraction was calculated as:ECV=(1-hematocrit)(1/(T1my post)-1/T1myopre)/(1/(T1blood post)-1/T1bloodpre)

Results:
AF patients had larger left atrial volume (persistent AF: 175.7±65.9ml; paroxysmal AF: 116.7±43.6ml) than controls (76.6±12.8ml) (paroxysmal vs. control: P<0.01; persistent vs. control: P<0.01). Mean ECV of persistent AF patients was 31.8±3.9% in the basal segments, 30.5±4.8% in the mid-cavity segments, 32.0±4.8% in the apical segments, paroxysmal AF patients were 29.2±3.6%, 28.2±3.5%, 31.5±4.6% respectively, which were higher than the controls (basal: 24.7±2.3%, mid-cavity: 25.9±2.4%, apical: 28.2±4.0%, all P<0.05).

Conclusion:
ECV fraction could help to identify the diffuse LV fibrosis in patients with AF. The quantification could be a better solution for clinicians in diagnosing diffuse LV fibrosis.
Abstract 13516: Chronic inflammation, Albuminuria, and Hospital Admissions Among Adults With Hypertension: The National Health and Nutrition Examination Survey 2003-2012
Authors: Kuo Hsu-Ko , Gore Joel M
Published: April 2024

Background:
Although clinical factors such as advanced age, co-morbidities, or polypharmacy have been extensively documented as crucial predictors for hospitalizations, data examining the associations of preclinical disease indicators such as albuminuria and subclinical inflammation with hospitalization among people with hypertension are sparse.

Methods:
Data were from 5149 adults (>20 years) with hypertension in the National Health and Nutrition and Examination Survey 2003-2012. Overnight hospitalization during the past 12 months (H) was ascertained by questionnaire. C-reactive protein (CRP) was quantified by latex-enhanced nephelometry. Urinary albumin-to-creatinine ratio (UACR) was categorized into normal, microalbuminuria (MiA), and macroalbuminuria (MaA).

Results:
Both MiA (UACR 30-300mg/g) and MaA (UACR>300mg/g) were associated with H in patients with hypertension. In the full-adjusted model, odd ratios (ORs) of H were 1.74 (95% confidence interval [CI] 1.25-2.42) and 1.27 (95% CI 1.05-1.54), respectively, comparing participants with MaA and MiA to those without albuminuria. CRP>0.3mg/dL was associated with increased odds of H comparing with normal CRP (OR 1.31; 95%CI 1.06-.162). Subjects with both albuminuria and elevated CRP had higher odds of H than individuals with no albuminuria and normal CRP (Figure).

Conclusion:
Albuminuria and inflammation were independent correlates for H among adults with hypertension. There was an interaction of albuminuria and elevated CRP on H, suggesting that the presence of subclinical inflammation may amplify the effect of albuminuria on hospitalization in adults living with hypertension. We provided new information on role of preclinical biomarkers in hospitalization among community-dwelling adults with hypertension where data currently are not available.
Abstract 13624: Effect of Electrical Therapy Using Biphasic Defibrillators in the 2010 CPR Guidelines for Patients With Out-of-Hospital Cardiac Arrest due to Nonshockable Rhythm
Authors: Yagi Tsukasa , Nagao Ken , Tachibana Eizo , Yonemoto Naohiro , Shirai Shinichi , Takayama Morimasa , Nonogi Hiroshi , Saku Keijiro , Tani Sigemasa , Matsumoto Naoya , Hirayama Atsushi ,   The JCS-ReSS Study Group
Published: April 2024

Background:
The 2005 guidelines for cardiopulmonary resuscitation (CPR) with electrical therapy recommended a single shock plus an immediate 2 minutes of CPR instead of 3-shock sequences recommended in the 2000 guidelines. The 2010 guidelines have stressed that it is necessary to improve CPR quality. Each set of guidelines recommended a timely shock when non-shockable patients were found to be in shockable rhythm. Few data are available concerning this electrical therapy.

Methods:
From the data of the All-Japan Utstein Registry, a prospective, nationwide, population-based registry of out-of-hospital cardiac arrest (OHCA), we included adult patients who had OHCA due to cardiac etiology, in whom non-shockable arrest were recorded as an initial rhythm, and who received shock using biphasic AEDs after conversion from non-shockable arrest to shockable arrest by emergency medical service (EMS) personnel. Study patients were divided into three groups based on the different CPR guidelines; 3-shock protocol in the 2000 guidelines (2000G), 1-shock protocol in the 2005 guidelines (2005G), and 1-shock protocol in the 2010 guidelines (2010G). The primary endpoint was favorable neurological outcome at 30 days after OHCA.

Results:
Of the 5066 patients who met the inclusion criteria (figure). The figure shows the comparison of favorable neurological using biphasic AEDs in the three groups. Adjusted odds ratios for favorable neurological outcome were 2.5 (95% CI, 1.3 to 4.7) after the 2005G group and the 2010G group as compared with the 2000G group, and 0.8 (95% CI, 0.6 to 1.1) after the 2010G group as compared with the 2005G group.

ConclusioN:
The single-shock protocol using biphasic AEDs of the 2005 and 2010 guidelines were superior to the 3-shock protocol of the 2000 guidelines, but the single-shock protocol using biphasic AEDs of the 2005 and 2010 guidelines had similar 30-day favorable neurological outcome in patients with non-shockable cardiac arrest.
Abstract 13776: Interaction of Baseline Left Ventricular Volume and Dyssynchrony on Long Term Prognosis After Cardiac Resynchronization Therapy
Authors: Tayal Bhupendar , Delgado-Montero Antonia , Goda Akiko , Saba Samir , Risum Niels , Sogaard Peter , Gorcsan John
Published: April 2024

Background:
Baseline dyssynchrony by radial strain (≥130 ms) has been associated with favorable outcome after cardiac resynchronization therapy (CRT) in heart failure (HF) patients with widened QRS. Because LV dilatation is associated with more advanced disease that is less responsive to CRT, we hypothesized that dyssynchrony has less prognistic value in patients with severely dilated LVs.

Methods:
We prospectively studied consecutive 260 CRT patients with class II-IV HF, LV EF ≤35%, and QRS≥120 ms. Assessment of dyssynchrony was done at mid-LV level by radial strain. Patients were divided into two groups based on the median value of end diastolic volume (EDV). Outcome events were death, LV assist device or transplantation over 4 years after CRT.

Results:
Out of 260 patients studied, 20 (8%) had poor image quality and 3 (1%) were lost to follow-up. Based on a median EDV of 180 ml: 121 (51%) had EDV≥180ml and 116 (49%) had EDV <180ml. Patients with EDV≥180ml were more often male, with lower LVEF and were younger (p<0.05). Baseline dyssynchrony by radial strain was detected with a higher percentage in EDV≥180ml group (p=0.02). There were 87 (37%) outcome events over 4 years. In the group with EDV<180 ml, absence of dyssynchrony at baseline was associated with a significantly higher risk for events with adjusted hazard ratio 2.09, 95% confidence interval 1.05 to 4.17 (p=0.03) after adjusting for QRS duration, LBBB, ischemia and baseline LV EF. Dyssynchrony was not associated with events in those with more dilated LVs EDV≥180 ml (p=0.8).

Conclusions:
Significant baseline mechanical dyssynchony was of prognostic significance in CRT patients who had less LV dilatation. In contrast, baseline dyssynchony was not associated with outcomes after CRT in those with more severely dilated LVs, which may represent more advanced LV disease that is less responsive to CRT.
Abstract 13792: Molecular Imaging of Activated Platelets using Positron Emission Tomography: A Novel, Highly Sensitive Detection Method for Cardiac Ischemia
Authors: Ziegler Melanie , Alt Karen , Hagemeyer Christoph E , Peter Karlheinz
Published: April 2024

Introduction:
Coronary artery disease (CAD) causing symptomatic ischemia is often missed in patients that present with angina pectoris but without ECG changes or rise in troponin. A sensitive diagnostic test that could diagnose an ischemic event, before cardiac damage is causing troponin release, would change the clinical path of emergency patients with angina and reduce the number of CAD patients to remain undiagnosed and thus have an increased risk of myocardial infarction.

Methods:
We developed a sensitive, non-invasive imaging approach using PET imaging of activated platelets for the detection of minimal cardiac ischemia and inflammation. Different extents of ischemia were induced in mice by temporary LAD ligation for 10, 20 or 60 min. Activated platelets were imaged in a PET/CT scanner with
64
Cu bound to the chelator MeCOSar that was conjugated to a single-chain antibody directed against activated GPIIb/IIIa.

Results:
A time course of platelet adhesion within the infarcted myocardium indicates an early inflammatory response of activated platelets to the ischemic insult peaking 2h post reperfusion. Sensitive biomarkers such as troponin I and heart-type fatty acid-binding protein (H-FABP) could not detect smaller degrees of cardiac ischemia (10 and 20 min of ischemia). In contrast, PET-based imaging of activated platelets detects even minor degree of ischemia. The significant adhesion of platelets in the ischemic heart even after minor degrees of ischemia was confirmed by flow cytometry and histology.

Conclusions:
Cardiac ischemia is associated with a significant adhesion of activated platelets within the ischemic heart. Even minimal extents of cardiac ischemia not associated with troponin rises are detectable by platelet-based PET imaging. This novel, highly sensitive non-invasive detection of minimal degrees of cardiac ischemia has the potential to detect otherwise undetected CAD.

Figure:
PET/CT imaging of activated platelets within ischemic hearts.
Abstract 13814: Cognitive Impairment is Independent of Depression and Anxiety in Predicting Death and Readmissions Within 30 Days of Discharge for Heart Failure
Authors: Huynh Quan L , Negishi Kazuaki , Blizzard Leigh , Saito Makoto , De Pasquale Carmine , Hare James , Leung Dominic , Stanton Tony , Sanderson Kristy , Venn Alison , Marwick Thomas
Published: April 2024

Background:
Cognitive impairment, depression and anxiety are common in heart failure (HF). This study investigated the relationship of these factors with short-term outcomes in HF.

Methods:
This study included 343 HF patients from an Australia-wide longitudinal study of HF. Baseline clinical and administrative data, mental health (PHQ-9 and GAD-7 scores), cognitive function (MOCA score) and 2D echocardiograms were collected before hospital discharge. The study outcomes were death and readmission within 30 days of discharge. Logistic regression, Harrell’s C-statistic and integrated discrimination improvement were used for analysis.

Results:
Of 343 HF patients, 60 (17%) had severe depression (PHQ-9>15), 43 (12%) had severe generalized anxiety (GAD-7>15), and 233 (68%) were cognitively impaired (MOCA<26). PHQ-9 and GAD-7 scores were closely correlated (r=0.76 p<0.001), but were not associated with the MOCA score (r=0.00 and r=0.01 respectively). Within 30 days of discharge, 21 (6%) patients died and 77 (22%) and were readmitted. Death and readmission within 30 days of discharge were more likely to occur among patients with severe depression (odds ratio OR=2.52, p=0.007), severe anxiety (OR=2.46, p=0.01) and cognitive impairment (OR=2.80, p=0.001). After adjusting for standard clinical predictors included in the Yale prediction model, MOCA score (OR 0.87 p<0.001), PHQ-9 score (OR=1.06 p=0.003) and GAD-7 score (OR=1.06 p=0.002) remained predictive of HF 30-day readmission or death. Compared with a basic clinical predictive model, MOCA, GAD-7 and PHQ-9 scores provided incremental value (integrated discrimination improvement estimate 0.129, p<0.001) in predicting 30-day death and readmission among HF patients (see Figure).

Conclusions:
Depression/anxiety and cognitive impairment are independent and incremental to standard predictors of short-term outcomes in HF.
Abstract 13829: The Active Metabolite of Selexipag Relaxes Rat Pulmonary Artery via Selective Activation of IP Prostacyclin Receptors
Authors: Morrison Keith , Ernst Roland , Haag Franck , Bur Daniel , Clozel Martine
Published: April 2024

Introduction:
Selexipag is a selective IP prostacyclin receptor agonist in development for the treatment of pulmonary arterial hypertension. Preclinical studies demonstrate that selexipag and its active metabolite ACT-333679 relax rat extralobar pulmonary artery (EPA)
ex vivo
. It has been reported that the IP receptor antagonist CAY10441 does not inhibit relaxation to ACT-333679.

Hypothesis:
We hypothesized that relaxation of rat EPA to ACT-333679 could be inhibited by antagonism of IP receptors using a modified protocol.

Methods:
Rings of rat EPA were prepared using standard techniques. Relaxation to ACT-333679 was measured in EPA pre-contracted with PGF
2
α
(10 μM). The effect of CAY10441, BWA868C and PF04418948 (selective antagonists of relaxant IP, DP
1
and

EP
2
receptors, respectively) on relaxation to ACT-333679 was measured using 2 protocols: (1) EPA was incubated with each receptor antagonist
prior
to addition of increasing concentrations of ACT-333679; (2) each receptor antagonist was added
after
stabilization of relaxation to ACT-333679 (1 μM).

Results:
ACT-333679 relaxed EPA in a concentration-dependent manner (Figure 1A; control pEC
50
5.8 ± 0.1). CAY10441 (1 μM) did not inhibit relaxation to ACT-333679 when added prior to ACT-333679 (pEC
50
5.6 ± 0.1; not statistically significant vs control). However, CAY10441 (0.1-10 μM) reversed relaxation of EPA when added after sub-maximal relaxation to ACT-333679 (1 μM) was reached (relaxation 48.8 ± 9.8% of PGF
2
α
contraction) (Figure 1B). BWA868C and PF04418948 did not inhibit relaxation of EPA when added before or after ACT-333679.

Conclusion:
Relaxation of EPA to ACT-333679 is inhibited by antagonism of IP receptors, but not DP
1
or EP
2
receptors. IP receptor activation by ACT-333679 is first required to observe the inhibitory effect of CAY10441 on vasorelaxation. ACT-333679 relaxes rat EPA via selective activation of IP prostacyclin receptors.
Abstract 13844: Microrna-126 and Microrna-132 Abrogates Deleterious Effects of Diabetes-induced Impaired Angiogenesis
Authors: Rawal Shruti , Munasinghe Emani , Manning Patrick , Katare Rajesh
Published: April 2024

Background:
Diabetes-induced microvascular abnormalities are implicated in altering cardiac function and structure, a condition referred as diabetic microangiopathy in heart (DMAH). Endothelial-enriched microRNAs (angiomiRs) have been recently demonstrated to play a major role in regulating angiogenesis. However, their pathophysiological role in development of DMAH is elusive.

Objective:
To investigate the modulation of angiomiRs (miR-126, miR-132) with evolution of DMAH and demonstrate if restoration of angiomiRs can improve functional properties of high glucose treated endothelial cells.

Methods & Results:
Cardiac tissues were collected from type-2 diabetic mice (BKS.Cg-m+/+Leprdb/J) every 4Wks, from 8 to 32Wks of age. qPCR revealed significant downregulation of miR-126 and -132 starting at 12Wks and continued till 32Wks (miR-126: 0.30±0.03; miR-132: 0.22±0.05,p<0.001 vs. age matched non-diabetic). This was associated with concomitant dysfunction of cardiac functions (assessed through echocardiography). Western blotting analysis confirmed marked dysregulation of VEGF and p120RasGap (P<0.05 vs. non-diabetic), the target proteins for miR-126 and -132, respectively. Importantly, immunohistochemical analysis did not show any noticeable changes in capillary density and arterioles until 20Wks in diabetes. To determine if restoration of miR-126 and -132 could reduce the development of DMAH, high glucose (HG)-treated Human Umbilical Vein Endothelial Cells (HUVECs) were transfected with either miR-126 or -132 mimics. Results showed that restoration of both the miRs markedly improved angiogenesis, assessed by tube formation assay (NG-Control- 8824±212; HG-Control: 3570±304; HG-126: 8970±184; HG-132: 7227±228), proliferation (CyQUANT cell proliferation assay) and reduced cell death (caspase-3/7 assay), p<0.05 for all the parameters. Of note, overexpression of miR-126 alone tends to restore the expression of miR-132 and vice versa in HG-treated HUVECs, suggesting an orchestrated role of miRs in regulating angiogenesis.

Conclusion:
Modulation of miRs occur much earlier before the development of DMAH and restoration of DMAH from early stages in HUVECs exposed to high glucose markedly improved their angiogenic potential.
Abstract 14197: Industrial Developmental Toxicant Emissions and Congenital Heart Disease in Urban and Rural Alberta, Canada
Authors: Ngwezi Deliwe P , Hornberger Lisa K , Serrano-Lomelin Jesus , Fruitman Deborah , Osornio-Vargas Alvaro
Published: April 2024

Background:
We have previously demonstrated a downward temporal association between mixtures of organic solvents released into air from industrial sources and congenital heart disease (CHD) in Alberta.

Hypothesis:
In the current study we hypothesized that the downward temporal associations between developmental toxicants (DTs) and CHD would have a different industrial sector participation in the urban and rural areas of Alberta.

Methods:
We extracted yearly emissions of DTs (tonnes) from Canada’s National Pollutant Release Inventory as released to air between 2003-2010. We identified at the postal code level, all CHD cases born between 2004-2011 through our provincial-wide echocardiography database. We calculated yearly urban and rural CHD crude rates. Urban and rural were defined according to Forward Sortation Areas. Principal Component Analysis was undertaken to reduce the dimensionality of the number of DTs and the yearly solution was applied to rural and urban areas to test correlations with corresponding yearly CHD rates.

Results:
Three principal components (PCs) were identified: PC1 consisted of a mixture of organics and gases, PC2 consisted of a mixture of organics only and PC3 consisted of metals. There were strong positive correlations between CHD rates and urban PC1 emissions from mining and manufacturing, (r=0.76, p=0.03; 0.74, p=0.04); whereas in rural areas, PC1 emissions from mining and utilities and PC2 emissions from mining and manufacturing were associated with rates of CHD, (r=0.71, p=0.05; r=0.74, p=0.04 and r=0.86, p=0.01; r=0.74, p=0.04, respectively). PC3 showed no positive correlations (Table 1).

Conclusions:
CHD rates are consistently strongly correlated with mixtures of organic compounds and gases, with different patterns of chemicals and sectors involved in the urban and rural settings. This provides an opportunity to further investigate spatial correlations between DTs and CHD rates at a higher resolution scale.
Abstract 14274: Characteristics and Natural History of Hospitalized Heart Failure Patients With Diabetes Mellitus: Preserved versus Reduced Ejection Fraction
Authors: Wan Siu-Hin , Slusser Joshua P , Hodge David O , Chen Horng H
Published: April 2024

Introduction:
Among those hospitalized with heart failure, diabetes (DM) is a common comorbid condition and the population characteristics and natural history of those with preserved EF (HFpEF) versus those with reduced EF (HFrEF) remain undefined.

Hypothesis:
To determine the epidemiologic profile and natural history among those hospitalized with acute heart failure (AHF) with DM and compare outcomes of those with reduced versus preserved EF.

Methods:
A retrospective chart analysis of adults hospitalized with primary ICD diagnosis of AHF from Olmsted County hospitalized from 2005 - 2008, with follow up until 2013. Demographic, clinical and lab data were collected.

Results:
Of 912 subjects hospitalized with AHF, 381 (42%) had DM. Among subjects with AHF and DM, those with HFrEF were similar in age to those with HFpEF (76.3±11.7 years vs 78.3±11.2 years, p=0.12), but were more likely to be male (58% vs 37%, p<0.001). Those with DM and HFrEF compared to HFpEF had less hypertension (95% vs 99%, p=0.046), but more coronary artery disease (89% vs 75%, p<0.001), prior myocardial infarction (65% vs 33%, p<0.001), and higher BNP values (1155±906 pg/mL vs 676±568 pg/mL, p<0.001). E/e’ ratio was similar in those with DM and HFrEF versus HFpEF (22.6±10.4 vs 21.7±10.9, p=0.49), suggesting both groups had increased filling pressures. There was no difference in mortality between the HFrEF and HFpEF groups up to 5 years in either the DM group (p=0.46) or the non-DM group (p=0.11). However, those hospitalized with AHF and DM demonstrated a higher rate in those with HFrEF versus HFpEF groups in all cause rehospitalization (p=0.019) and heart failure rehospitalization (p=0.008). This was different from the non-DM group, where there was no difference between HFrEF and HFpEF in all cause hospitalization (p=0.31) or heart failure rehospitalization (p=0.19).

Conclusions:
In patients hospitalized for AHF with DM, those with HFrEF had increased all cause and heart failure hospitalization as compared to HFpEF. In contrast, subjects without DM had no differences in rehospitalization between the HFrEF and HFpEF groups. Further studies are warranted to define pathophysiological mechanism for this observation.
Abstract 14292: Living Heart Human Model: Pacemaker Lead Insertion and Cardiac Cycle Simulation
Authors: Saraswat Prabhav , D'Souza Karl , Baillargeon Brian P
Published: April 2024

Introduction:
The durability of the pacemaker electrodes is of great importance since damage to them can mean they no longer provide life-saving electrical stimulus. A pacemaker electrode is meant to be a permanent implant, where it is expected to perform for many years without failure. The
SIMULIA Living Heart Human Model
provides a unique testing environment where a pacemaker electrode can be virtually inserted and mechanically deformed during the cardiac cycle. The virtual nature of the test provides a physiologically accurate methodology to test new and existing devices without exposing patients to un-necessary risk. Further, the computational model allows for hundreds of virtual experiments, where parameters such as lead diameter, stiffness and location are varied to select the design and placement that have optimal reliability

Methods:
The SIMULIA Living Heart Human Model is a high-fidelity multiphysics finite element model of a healthy, 4-chamber adult human heart and proximal vasculature. The pacemaker lead was inserted into the right atrium and ventricle through the superior vena cava. The heart model then completes 3 cardiac cycles to determine the deformation of the electrode.

Results:
The primary mode of deformation to cause damage is bending; therefore, curvature change of the pacemaker electrode is the output quantity of primary interest. The plot below shows the curvature (left) and maximum alternating curvature (right) along the length of the pacemaker electrode throughout the cardiac cycle.

Conclusions:
The results demonstrate the feasibility of utilizing a high-fidelity heart model to estimate the amount of deformation experienced by a pacemaker electrode during the cardiac cycle. This work, coupled with empirical fatigue testing of the implant, will allow for durability calculations to be made of existing and new electrode designs.
Abstract 14341: A Depressed Cardiac Output in Patients With Advanced Heart Failure is Not Accompanied by Increased Plasma Lactate Levels in the Majority of Patients: Is it Time for a New Definition of Heart Failure?
Authors: Adamo Luigi , Nassif Michael , Larue Shane , Mann Douglas L
Published: April 2024

Introduction:
Heart failure (HF) has been defined as a condition in which the heart is unable to deliver sufficient oxygen to match the needs of the metabolizing tissues. This definition, which was based on observations in patients with terminal HF, has never been validated. Moreover, the application of this definition led to the use of inotropes , and discouraged the use of beta-blockers, delaying the development of appropriate HF therapies.

Methods:
To determine whether the heart was unable to meet the metabolic demands of the body, we retrospectively analyzed Arterio-Venous oxygen difference (AV O2) and plasma lactate levels in NYHA class IV heart failure patients that subsequently received a Left Ventricular Assist Device (LVAD).

Results:
We identified 359 patients with a right heart catheterization (RHC) performed prior to LVAD implantation. Plasma lactate was available for 96 patients. RHC showed that 93% of the patients had an AV O2 difference above normal (> 5 ml/100 ml). Among patients with measured lactate levels the prevalence of elevated lactate (> 2.1 mmol/L) was only 25% (95% CI 16.7-34.9). AV O2 was widened in all patients with elevated lactate, but plasma lactate did not correlate with AV O2 (R=0.02) and only 27% of patients with increased AV O2 had elevated plasma lactate (
Figure
). Patients with widened AV O2 and elevated lactate were sicker than patients with widened AV O2 and normal lactate, as shown by a higher prevalence of low INTERMACS class, elevated INR and reduced serum albumin. However, there was no obvious hemodynamic difference between the two groups.

Conclusions:
Approximately 75% of the patients in this NYHA class IV HF sample with a depressed cardiac output had normal lactate levels, suggesting that cardiac output was sufficient to meet the metabolic demands of the body. Given that approximately 4% of HF patients are NYHA class IV, these findings suggest that the classic definition of heart failure may be valid in only 1% of the total heart failure population.