bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18980: Aortic Distensibility May Be Associated With the Characteristics of Coronary Atherosclerosis Plaque
Authors: Hong Seung-Pyo , Bae Kyung-Ryun , Jun Seung-Woon , Lee Young-Soo , Lee Jin-Bae , Ryu Jae-Kean , Choi Ji-Yong , Kim Kee-Sik , Chang Sung-Gug
Published: April 2024

Purpose:
Aortic distensibility (AD) has been shown to be inversely proportional to disease severity and presence of cardiovascular risk factors. MDCT can simultaneously characterize coronary and thoracic aortic atherosclerotic plaque morphology by delineating between calcified, mixed, non-calcified lesions. This study aimed to access relation between the characteristics of coronary plaque and AD in cardiac MDCT.

Methods:
The study was a retrospective analysis of the findings in 69 patients who performed cardiac MDCT for evaluation of chest pain symptoms. The 69 subjects was performed 64 channel cardiac MDCT and Scan data were reconstructed at 20 phases between 0% and 95% of the R-R intervals with an increment of 5%. Pixel-based measurements of arterial dimensions were performed at 1 cross-section of the descending aorta in a transverse plane at the aortic valve level. End diastole area was measured at 95% of R-R interval and end systolic area was measured at 35% of R-R interval. Aortic distensibility was calculated as follows: AD= (end systolic area - end diastolic area)/ (end diastolic area х pulse pressure). Coronary plaques in cardiac MDCT were categorized as calcified, mixed, or non-calcified.

Results:
Descending AD were lower in patients with any coronary plaque, calcified or mixed plaque than those without (mixed: p<0.001, calcified: p=0.041) but not with non-calcified coronary plaque (p=0.497). In multivariate logistic regression analysis, descending AD (p = 0.011, HR 6.446) is independently associated with mixed coronary plaque after adjustment of age, sex, body mass index. The cutoff value of descending AD for prediction of mixed plaque in cardiac MDCT was 1.6 X 10
-3
mmHg with 69.2% of sensitivity and 69.2% of specificity (Fig).

Conculsions:
Descending AD may be associated with the mixed or calcified plaque in by MDCT. Especially, Descending AD might be associated with mixed coronary plaque.
Abstract 18987: Warning Symptoms Precede Sudden Cardiac Death in Majority of Men
Authors: Marijon Eloi , Reinier Kyndaron , Evanado Audrey , Teodorescu Carmen , Narayanan Kumar , Huertas Vazquez Adriana , Chugh Harpriya , Jerger Katherine , Mariani Ronald , Stecker Eric , Gunson Karen , Jui Jonathan , Chugh Sumeet
Published: April 2024

Introduction:
Despite significant enhancements in resuscitation methodology, survival after sudden cardiac arrest (SCA) remains low. Improved knowledge of warning signs and symptoms may assist the process of early intervention for SCA.

Hypothesis:
We hypothesize that a sub-group of men who suffer SCA have warning symptoms prior to SCA.

Methods:
In a large, ongoing, prospective, population-based study in a Northwestern US metro region (population approx. 1 million; 2002-2012), we systematically evaluated the frequency, characteristics and temporal trends of all symptomatology in the 4 weeks prior to SCA among middle aged male cases (35-65 years). We performed a detailed and comprehensive assessment of the accounts of family members/relatives, witnesses, emergency medicine personnel, as well as medical records during this time period.

Results:
Of the 825 SCA cases, 258 (31%) did not have sufficient information to ascertain the presence of symptoms. Of the 567 cases with appropriate assessment [mean age 52±12 yr, initial shockable rhythm 59%, presence of witness 40%, bystander CPR 27%, presence of coronary artery disease (CAD) 84%], 300 (53%) patients presented with symptoms. These were principally chest pain in 167 patients (56%), dyspnea in 38 (13%), and dizziness/syncope/palpitations in 11 (4%). Episodes of chest pain were categorized as typical angina in 111 (67%) and suspicion of angina in 56 (33%). In an additional 29 cases (10%), typical flu symptoms were noted during the 4 weeks period. Overall, most symptoms (79%) occurred more than 1 hr before the SCD event (up to 4 weeks), whereas symptoms immediately preceding (<1 hour) were less frequent (21%). Symptoms were especially frequent with associated CAD compared to non CAD-related SCA (56% vs. 32%, P=0.0005). Among patients with previously known CAD 55% had symptoms before SCA.

Conclusions:
In this community-based study, a higher than expected proportion of middle-aged men had warning symptoms prior to SCA. These findings may be explained by longer duration of evaluation, and have implications for SCA surveillance and prevention.
Abstract 19013: Symptomatic Spontaneous Automaticity in a Decrementally Conducting Left Free Wall Accessory Pathway in a Patient With Congenital Heart Block
Authors: Shah Alap P , Trohman Richard , Krishnan Kousik , Madias Christopher
Published: April 2024

Introduction:
A 20 year-old female with a history of a coil-occluded patent ductus arteriosus and congenital complete atrioventricular (AV) block was admitted for a wide complex tachycardia (WCT) associated with palpitations and dizziness. Her LV function was normal and no additional structural heart disease was noted on a cardiac MRI. Electrophysiology (EP) study was performed.

Methods:
N/A

Results:
EP study showed sinus tachycardia with 1:1 antegrade conduction via a left-sided accessory pathway. The accessory pathway demonstrated decremental conduction, adenosine responsiveness, and no retrograde conduction. The earliest ventricular activation was noted in the distal coronary sinus electrode. At slower atrial rates (70-100 bpm), there was isorhythmic dissociation (see figure) between the accessory pathway (QRS identical to maximal pre-excitation) and the sinus node strongly suggesting spontaneous accessory pathway automaticity. The accessory pathway was successfully ablated by targeting an accessory pathway potential located at the anterior aspect of the mitral valve. Post-ablation, there was complete AV block with a narrow junctional escape rhythm at a rate of 64 beats per minute. The patient underwent placement of a dual chamber pacemaker.

Conclusion:
This is, to our knowledge, the first reported case of a left-sided accessory pathway with both spontaneous automaticity and Mahaim-like properties.
Abstract 19038: Epigenetic Regulation of Canonical TNFa Pathway by HDAC1 Determines Survival of Cardiac Myocytes
Authors: Kirshenbaum Lorrie , Gang Hongying , Shaw James , Dhingra Rimpy
Published: April 2024

Gene transcription is regulated by post-translation modifications. Histone deacetylases (HDACs) remove acetyl-groups from histone and non-histone factors inhibiting transcription. Pro-inflammatory cytokines such as TNFα activate the canonical Nuclear Factor -κB (NF-κB) pathway. Earlier we established a cytoprotective role for NF-κB in the heart. Though a causal relationship for HDAC1 and NF-κB has been established, the impact of HDAC1 on TNFα signaling is unknown. Herein, we demonstrate HDAC1 provides a molecular switch for determining cell survival in the TNFα pathway. In contrast to vehicle treated control cells, TNFα treated cells displayed a marked increase in NF-κB gene transcription. Notably, cells treated with TNFα were indistinguishable from vehicle controls cells with respect to viability. Interestingly, HDAC activity was reduced in cells treated with TNFα. Conversely, in the presence of HDAC1, NF-κB gene transcription by TNFα was repressed, resulting in mitochondrial perturbations and widespread cell death. Heterologous fusion proteins comprised of yeast Gal4 DNA binding domain fused in frame to the NF-κB p65 transactivation domain were preferentially repressed by HDAC1. Moreover, transcription mediated by Gal4VP16 protein from herpes virus was unaffected by HDAC1 in cardiac myocytes. Mutations that abrogate known catalytic activities of HDAC1, small interference RNA or pharmacological inhibition of HDAC1, restored NF-κB signaling and suppressed cell death induced by TNFα. These data provide the first evidence for an obligate link between HDAC1 and canonical TNFα pathway for cell survival of cardiac myocytes.
Abstract 19049: MiR-126 Containing Exosomes From Human CD34+ Stem Cells Activate Endothelial Cells to Initiate Angiogenesis and Ischemic Tissue Repair
Authors: Sahoo Susmita , Misener Sol , Kim David , Thorne Tina , Vaughan Douglas E , Losordo Douglas W
Published: April 2024

Introduction:
Locally transplanted human CD34+ stem cells have been shown to improve exercise tolerance in patients with myocardial ischemia and promote angiogenesis in animal models. Recently we have demonstrated that CD34+ cells secrete membrane bound nano-vesicles called exosomes as a major component of their pro-angiogenic paracrine secretion.

We hypothesize that cell-free exosomes from CD34+ cells (CD34 Exo) mimic the beneficial effects of the cells and promote angiogenesis and ischemic tissue repair via transfer of pro-angiogenic microRNAs, possibly to endothelial cells.

Methods and Results:
Therapeutic potential of CD34 Exo isolated from equal number of adult human peripheral blood-derived CD34+ cells was evaluated in an immunodeficient murine model of hind limb ischemia. Similar to cells, treatment with CD34 Exo resulted in significant improvement in ischemia compared to treatment with PBS (perfusion ratio: 1.01±0.04 v 0.57±0.1; capillary density: 1.8±0.3 v 0.9±0.1/HPF; limb amputation: 16% v 100%; p<0.05; n=10-21). MicroRNA expression profiling and confirmatory tests indicated that CD34 Exo are significantly enriched with pro-angiogenic miRNAs such as miR126. Treatment with CD34 Exo in mouse hind limb ischemic tissue increased mature miR126 expression, but not endogenous mouse pri-miR126, and activated pro-angiogenic miR126 target-gene expression. Treatment of CD34 Exo lacking miR126 abolished this increase and diminished the pro-angiogenic function of CD34 Exo-treated endothelial cells. This data suggests that miR126 is important for CD34 Exo function. Interestingly, confocal imaging and flow cytometry analyses revealed that CD34 Exo were selectively internalized by endothelial cells when injected to the ischemic tissue. Live imaging using fluorescent miR126 confirmed that CD34 Exo directly transfers miR126 and possibly other yet to be identified moieties from its repertoire specifically to endothelial cells in the ischemic tissue.

Conclusion:
CD34+ exosomes transfer miR126 to endothelial cells to induce angiogenesis and ischemic tissue repair. The functional benefits associated with CD34+ cell therapy may be mediated by exosomes-mediated targeted transfer of angiogenic microRNAs to endothelial cells.
Abstract 19069: Autoregulation of Connexin43 Gap Junction Formation by Internally Translated Isoforms
Authors: Smyth James W , Shaw Robin M
Published: April 2024

During each heartbeat, cell-cell electrical coupling via connexin 43 (Cx43) gap junctions allows billions of individual cardiomyocytes to synchronously contract. The Cx43 protein turns over rapidly, rendering regulation of Cx43 trafficking a critical and continuous cellular need. Altered Cx43 trafficking during heart disease disrupts intercellular coupling and can contribute to the arrhythmias of sudden cardiac death. Better understanding of how Cx43 channels are transported to the cell surface will lead to therapies that can preserve normal electrical coupling of diseased heart muscle. We have identified a novel regulatory mechanism whereby internal translation of the coding sequence of Cx43 (
GJA1
) mRNA generates N-terminally truncated isoforms that regulate trafficking of full length Cx43 channels. Biochemical analysis of human heart and cell lines reveals at least four additional Cx43 isoforms, with a 20 kDa isoform predominating. We find that in frame AUG codons within
GJA1
mRNA represent isoform translation initiation sites and that their ablation arrests trafficking of full-length Cx43. The predominant 20 kDa isoform is sufficient to rescue this trafficking defect when expressed
in trans
, implicating an essential role as a trafficking chaperone for Cx43. Consistent with these data, expression of Cx43 truncated isoforms is enhanced through inhibition of the PI3K/AKT/mTOR pathway in cardiomyocytes, and concomitantly increases Cx43 gap junction plaque size. Such cap-independent internal translation initiation events may represent a common mechanism for auto-regulation of membrane protein trafficking which is likely altered during stress and, based on these studies, represents a potent target for therapeutic preservation of intercellular coupling in heart disease.
Abstract 19073: Geographic Classification Scheme for High-Risk Neighborhoods for Cardiovascular Disease in Texas
Authors: Walker Kyle , Crotty Sean M
Published: April 2024

There is substantial evidence that neighborhood characteristics have a significant impact on residents’ health outcomes. Our intent in this study was to create a classification system based on differences between high-risk neighborhoods for cardiovascular health in Texas. To accomplish this goal, we drew a total sample of 13 million cases of cardiovascular disease treatment from the 2006 Texas Hospital Inpatient Discharge Public Use Data File. These cases were then geo-coded to Zip Code Tabulation Areas (ZCTA’s) and age-adjusted hospitalization rates were calculated for each ZCTA. The top quartile of all ZCTA’s were retained for a factor and k-means cluster analysis, which used ten carefully selected socio-economic variables, to differentiate between high risk neighborhoods for cardiovascular disease. Based on this analysis, we identified four types of high-risk neighborhoods in the state. These include largely white areas in rural Texas; inner-city African-American neighborhoods; heavily Hispanic neighborhoods in large cities and the Rio Grande Valley; and diverse, working-class suburbs. . These clusters demonstrate the complexity of neighborhood effects on cardiovascular disease, as well as the linkages between race and poverty, and hospital admissions. In conclusion, in order for the American Heart Association to reach its goal of reducing cardiovascular disease and death by 20 percent by 2020, outreach and policy must be crafted to reach particular groups, and be delivered in ways that reach those particular types of neighborhoods. The classification system presented in this paper provides a framework for just such a project.
Abstract 19085: Outcomes After Cardiopulmonary resuscitation With Chest Compressions Only versus Conventional CPR: A Meta-Analysis of 84,888 Patients
Authors: Vallakati Ajay , Reddy Madhu Y , Yarlagadda Vivek , Murugiah Karthik , Janga Pramod , Maybrook Ryan , Mahankali Sridhar Arun Raghav , Atkins Donita , Bommana Suddharani , Natale Andrea , Lakkireddy Dhanunjaya
Published: April 2024

Objectives:
Optimal method of by-stander cardiopulmonary resuscitation (CPR) is still controversial. Studies comparing “chest compressions only CPR” with “conventional CPR” have yielded mixed results. We intended to compare the effectiveness of the above two strategies on survival after cardiac arrest out of hospital by performing a meta-analysis of all available clinical studies till date.

Methods:
We searched Medline and Embase for randomized control trials (RCT) and prospective observational studies comparing “chest compressions only CPR” with “conventional CPR”. Only studies presenting survival outcomes were included. Random effects model with inverse variance weighting was used to calculate pooled risk ratio (RR). Subgroup analyses were also performed as deemed necessary.

Results:
We identified 15 studies (12 observational and 3 RCTs) including 84,888 patients, of whom 39,572 received chest compressions only and 45,316 received conventional CPR. There was no significant difference in the survival with either technique (RR: 1.08; 0.93 - 1.26, p = 0.33). Exclusion of one study which reported only neurologically favorable survival did not alter the composite analysis. There was a significant heterogeneity among the studies (I2 = 85%, p<0.001). Begg’s and Egger’s regression test did not reveal any publication bias. Sub-group analyses of observational studies (RR: 0.97; 0.85-1.12, p=0.71) and RCTs (RR: 1.6; 0.88 - 3.1, p =0.12) did not demonstrate any difference in the survival outcome between the two techniques.

Conclusion:
By-stander “chest compressions-only CPR” is associated with similar survival rate when compared to “conventional CPR”.
Abstract 19092: Cyclooxygenase 2 Mediates Increased Endothelium-Dependent Vascular Contraction in Hyperhomocysteinemia and Hyperlipidemia
Authors: Cheng Zhongjian , Jiang Xiaohua , Durante William , Kruger Warren D. , Yang Xiaofeng , Wang Hong
Published: April 2024

Objectives:
We recently reported that elevation of plasma homocysteine level_hyperhomocysteinemia (HHcy) accelerates atherosclerosis and vascular inflammation in hyperlipidemia (HLP). In this study, we examined the role of cyclooxygenase 2 (COX2)[[Unable to Display Character: —]]an inducible isoform of COX in responsible to inflammation, in HHcy/HPL-induced endothelial dysfunction (ED).

Methods:
Endothelial function was assessed in the thoracic aorta of a novel severe HHcy (plasma Hcy=221 μM) mouse model: human cystathionine β-synthase (CBS) transgenic, mouse CBS and apolipoprotine E gene deficient mouse fed with a high fat diet for 8 weeks (HHcy/HLP Cbs-/-¬ mice).

Results:
Endothelium-dependent relaxation to acetylcholine (ACh) was significantly impaired in HHcy/HLP Cbs-/- mice compared to HHcy/HLP Cbs+/+ mice. In the presence of eNOS inhibitor N(G)-nitro-L-Arg-methyl ester (L-NAME), ACh induced endothelium-dependent contraction in HHcy/HLP Cbs-/- but not in HHcy/HLP Cbs+/+ mice. L-NAME plus COX1/2 inhibitor indomethacin (INDO) completely blocked the HHcy/HLP-induced endothelium-dependent contraction. Moreover, INDO, COX2 inhibitor nimesulide, and thromboxane A2/prostaglandin H2 receptor antagonist SQ29548, but not COX1 inhibitor SC560, improved vascular relaxation to ACh in HHcy/HLP Cbs-/-¬ mice, indicating that COX2 plays a major role. Preincubation the aorta with antioxidants Tempol, polyethylene glycol superoxide dismutase and apocynin also improved endothelial function in HHcy/HLP Cbs-/- mice. Expression of COX2 and 3-nitrotyrosin (3-NT), but not COX1, was markedly increased in the endothelium of aorta of HHcy/HLP Cbs-/- mice. ICAM-1, VCAM-1, and TNFα were markedly increased in the aorta of HHcy/HLP Cbs-/- mice. Moreover, COX2 and 3-NT, but not COX1, was significantly increased in cultured human aortic endothelial cells treated with a combination of DL-Hcy (500 μM) and oxidized-LDL (200 μg/ml) for 48 hrs. Furthermore, DL-Hcy/oxidized-LDL-induced COX2 was prevented by PEG-SOD. Finally, HHcy markedly accelerated urinary 2,3-dinor TXB2, TXB2, 8-isoprostan and 6-keto prostaglandin F1α levels in HPL.

Conclusions:
COX2 mediates HHcy-induced endothelium-dependent vascular contraction in HPL via oxidative stress-dependent pathway.
Abstract 191: During Lipid Resuscitation, Lipid-Blood-Fraction Rapidly Transports Radiolabeled-Bupivacaine From Highly Perfused Organs to Liver for Accelerated Processing and Excretion
Authors: Fettiplace Michael , Ripper Richard , Lis Kinga , Pichurko Adrian , Vitello Dominic , Weinberg Guy
Published: April 2024

Objective:
Lipid emulsions (LE) reverse local anesthetic cardiotoxicity but the mechanism of reversal is not completely understood. We tested the hypothesis that LE accelerates removal of radiolabeled-bupivacaine from highly perfused tissue and transports it to the liver for conjugation and excretion.

Methods:
Animals were anesthetized using 1.5-2% isoflurane. Jugular veins and right carotid artery were cannulated; a flow probe was hooked around the left common carotid. Flow, pressure and EKG were monitored continuously. Sixty Sprague-dawley rats received a 10mg/kg i.v. bolus of tritium-radiolabeled bupivacaine over 20-seconds with the end of infusion signaling t=0. Animals were assigned to eight sacrifice time-points (t=0.5, 1.5, 2.5, 4.5, 5.5, 8, 12, 60 minutes) and two treatment groups (i.v.LE, null). At t=0.5, animals in the test-group received 10mL/kg i.v.-LE over one minute. After sacrifice, tissues and fluids were collected and analyzed for radiolabeled-bupivacaine concentration.

Results:
Concentrations in heart, cerebellum, and kidney dropped more rapidly in i.v.-LE-treated animals (Figure 1) while concentrations in blood, liver and urine rose in a sequential order. Elevated whole blood concentration of radiolabelled-bupivacaine was driven by the LE component. The drops in organ concentration were associated with improvements in cardiovascular (CV) parameters (flow, RPP, mean arterial pressure) but improvements in i.v.-LE treated animals were greater than the improvements seen in null animals with comparable cardiac bupivacaine concentrations.

Conclusion:
The study confirms LE’s ability to sequester bupivacaine in vivo, reducing the concentration in vital organs and elevating liver concentrations. Further it is the first to demonstrate that LE accelerates processing and excretion into the urine. Finally, it builds on a growing body of evidence that LE improves CV dynamics that are beyond the pure removal of bupivacaine for CV tissue.
Abstract 19103: Revascularization Improves the Myopathy, Hemodynamics and Function of the Limbs of Patients With Peripheral Arterial Disease
Authors: Papoutsi Evlampia , Casale George P , Koutakis Panagiotis , Myers Sara , Thompson Jonathan R , Ha Duy , Swanson Stanley A , Zhu Zhen , Kim Kyung-Soo , Wurdeman Shane , Johanning Jason M , McComb Rodney D , Pipinos Iraklis I
Published: April 2024

Introduction:
Peripheral arterial disease (PAD), is characterized by myopathy, reduced hemodynamics and dysfunction of the ischemic legs. Two key characteristics of the myopathy of PAD limbs are myofiber degeneration and oxidative damage. We hypothesize that revascularization operations improve the myopathy of PAD limbs in association with improvements of hemodynamics and function.

Methods:
We recruited PAD patients undergoing open or endovascular revascularization of their ischemic legs. The gastrocnemius of these patients was biopsied, and limb hemodynamics (Ankle-Brachial Index, ABI) and function (six-minute walking distance and treadmill claudication walking times) were assessed before and six months after revascularization. Slide mounted specimens of the gastrocnemius biopsies were analyzed for biomarkers of myofiber oxidative damage (carbonyl groups and 4-hydroxy-2-nonenal adducts) and morphology (myofiber cross-sectional area, major axis, minor axis and equivalent diameter) by quantitative fluorescence microscopy.

Results:
Thirty claudicating patients underwent revascularization operations (21 open and 9 endovascular operations). Revascularization reduced oxidative damage observed as decreased carbonyl groups (13.4%, p<0.001) and 4-hydroxy-2-nonenal adducts (29.6%, p<0.001). Myofiber morphology improved as determined by increased cross-sectional area (18.1%, p<0.001), major axis (5.3%, p<0.05), minor axis (4.6%, p<0.05) and equivalent diameter (6.3%, p<0.01). ABI increased from 0.50±0.03 to 0.86±0.03 (p<0.001) and limb function improved as determined by increases of six-minute walking distance (25.9%, p<0.05), onset of claudication time (101.4%, p=0.001) and maximum walking time (236.3%, p=0.01).

Conclusions:
Revascularization operations improved the myopathy of PAD limbs in association with improvements in both hemodynamics and function.
Abstract 19104: The Relationship of Parent Well-Being, Family Management, and Service Utilization in Families of Children With Hypoplastic Left Heart Syndrome From the Perspective of Mothers and Fathers
Authors: Ballantyne Ross T , Dorfman Tamara , Dahl Nicole , Rogers Laura , Magill-Evans Joyce , Mackie Andrew , Rempel Gwen
Published: April 2024

Background:
Given the prevelance of neurodevelopmental impairments in children with hypoplastic left heart syndrome (HLHS), and recommendations that they have early intervention, parents’ patterns of service utilization for their at-risk child warrants investigation. The purpose of this study was to (1) delineate parent, child, and family needs from the perspective of parents, and (2) identify the services and resources used and needed by parents to support themselves, their children, and their family.

Method:
Descriptive study employing the Family Management Measure (FaMM), Connor-Davison Resilience Scale (CD-RISC), Parenting Stress Index (PSI), Vineland Adaptive Behaviour Scales (VABS) and Education and Rehabilitation Services Questionnaire (ERSQ).

Findings:
Questionnaires were sent to 64 families. Thirty-four parents, 21 mothers and 13 fathers, from 22 families returned questionnaires ( 38% response rate). Mean age of the children was 4.81 years (range 13 months to 15 years). There was no significant difference between the resilience of mothers and fathers, with 5/32 (19%) scoring in the post-traumatic stress category. For parenting stress, 10 of 30 (33%) of parents scored in the clinically significant range. Ten of 24 (41%) parents fell into the problematic family management category. Half of the children on the Vineland had typical or above average mean scores. Four of the 22 children living with severe morbidities were receiving education and rehabilitation services. Children with mild to moderate morbidities, including inattention, learning and behavior difficulties, progressive hearing loss and sensory issues, were not receiving adequate services. Minimal community-based services for parents were reported.

Conclusion:
The presence of an impairment such as HLHS does not predict service needs or outcomes from a functional perspective. Rather, persistent comorbidities have distinct meaning for each child, parent, and family. Therefore, when considering intervention for both the child and the parent, it is important to consider parents’ perceptions the child’s limitations and community participation and how these perceptions influence their parenting processes, especially related to service utilization.
Abstract 19186: Role of Exosomes and Their microRNA Constituents in Mediating the Therapeutic Benefits of Human Cardiosphere-Derived Cells in vitro and in Mice With Myocardial Infarction
Authors: Ibrahim Ahmed G , Cheng Ke , Marbán Eduardo
Published: April 2024

Background:
Exosomes are nano-sized bilayer vesicles that are secreted by most cell types. Exosomes are rich in microRNAs (mirs) which may function in a paracrine fashion. Cardiosphere-derived cells (CDCs) have been shown to regenerate heart after myocardial infarction (MI) in animal models and in the CADUCEUS clinical trial. However, most of the regenerated muscle is of innate origin, which suggests that CDCs function mainly through indirect pathways.

Methods and Results:
In vitro and in vivo, we compared three treatment groups: vehicle only (control), CDC-derived exosomes and normal human dermal fibroblast (NHDF)-derived exosomes. Neonatal rat cardiomyocytes (NRCMs) incubated with CDC exosomes were more frequently positive for Ki67 (n=4, p<0.001), and less frequently tunel-positive, compared to NHDF exosomes or control (n=4, p<0.01). CDC exosomes also stimulated tube formation in HUVEC cells compared to NHDF exosomes or control (p<0.05). SCID mice injected with exosomes from CDCs during acute MI showed higher LVEF at two weeks (n=6, p<0.05) and four weeks (n=6, p<0.05) post MI, as well as increased viable mass. The therapeutic benefits of exosomes were equivalent to those of 105 injected human CDCs (p=ns). Inhibition of exosome secretion by ceramide synthesis inhibition abrogated the beneficial effects by CDCs in vivo and in vitro. Mir microarray analysis identified mirs146a as the most highly-up regulated mirs in CDC-exosomes compared to NHDF (262-fold, n=4). Mir-146a-treated NRCMs were more resistant to H2O2-induced stress compared to a mimic control. Array analysis of these NRCMs treated also showed suppression of IRAK1 and TRAF6 transcripts. SCID mice injected with 80 ng of mir-146a during acute MI showed higher LVEF at two weeks (n=6, p<0.05) and four weeks (n=6, p<0.05) post MI, as well as increased viable mass compared to mimic control.

Conclusions:
Mir-containing exosomes secreted by CDCs exhibit multiple beneficial effects on injured myocardium, suggesting that exosomes may mediate some of the therapeutic effects of CDCs. Most notably mir-146a provides cardioprotection in an acute model of MI.
Abstract 19213: Long-Term Prognostic Value of and Serial Changes in Plasma N-terminal Pro B-type Natriuretic Peptide in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Ribeiro Henrique B , Nombela-Franco Luis , Urena Marina , Allende Ricardo , Le Ven Florent , Clavel Marie-Annick , Dahou Abdellaziz , Côté Mélanie , Laflamme Jerôme , Laflamme Louis , DeLarochelière Hugo , DeLarochelière Robert , Pibarot Philippe , Rodes-Cabau Josep
Published: April 2024

Background:
Little is known about the usefulness of evaluating cardiac neurohormones in patients undergoing transcatheter aortic valve implantation (TAVI). The objectives of this study were to evaluate the baseline values and serial changes of NT-proBNP following TAVI, its related factors and prognostic value.

Methods and Results:
A total of 333 consecutive patients undergoing TAVI were included. Baseline, procedural and follow-up (median: 20 [8 to 35] months) data were prospectively collected. Systematic NT-proBNP measurements were performed at baseline, hospital discharge, 1-month, 6- to12 months, and yearly thereafter. Baseline NT-proBNP values were elevated in 86% of the patients (median: 1692 [667-3910] pg/mL); lower left ventricular ejection fraction and stroke volume index, higher LV mass, and renal dysfunction were associated with greater baseline values (p<0.01 for all). Higher NT-proBNP levels were independently associated with increased long-term overall and cardiovascular mortality (P<0.001 for both), with a baseline cut-off level of ~2,000 pg/mL best determining poorer outcomes (P<0.001). At 6- to 12-month follow-up, NT-proBNP levels had decreased (P<0.001) by 23 (IQR: -62 to +32)% and remained stable up to 4-year follow-up. In 39% of the patients, however, NT-proBNP values increased to some degree. Pre-procedural chronic atrial fibrillation, lower mean transaortic gradient and moderate/severe mitral regurgitation were the predictors of the lack of NT-proBNP improvement after TAVI (P<0.01 for all).

Conclusions:
Very high NT-proBNP levels were observed in most TAVI candidates, which in turn predicted a higher overall and cardiac mortality after a median follow-up of approximately 2 years. TAVI was associated with a significant decrease in NT-proBNP levels over time, but a lack of improvement was observed in more than one third of the patients, mainly due to the presence of chronic atrial fibrillation, a lower transvalvular gradient and moderate-to-severe mitral regurgitation. These results strongly suggest the usefulness of implementing NT-proBNP measurements for the clinical decision-making process and follow-up of TAVI patients.
Abstract 19214: Inverse Relationships of Cardio-Ankle Vascular Index and Body Mass Index in Children
Authors: Philip Ranjit
Published: April 2024

Objective:
The epidemic of childhood obesity, with early onset of adult-type diseases like diabetes and hypertension, is creating a national health crisis. Cardio-ankle vascular index (CAVI), a non-invasive measure of vascular function, reflects the stiffness of arteries independently of changes in blood pressure (BP). There are currently no CAVI scores available for children. We hypothesized that CAVI, by providing an objective measure of vascular health, may help identify children at increased risk for cardiovascular disease.

Methods:
Study subjects were 292 Non- Hispanic White, Non- Hispanic Black, or Hispanic children 10-18 years old, normal weight (BMI85th percentile for age). CAVI values were measured using the VaSera VS-1500N device.

Results:
CAVI was measured in 292 children, with 133 males and 159 females, including 89 Black, 100 White and 103 Hispanic children. After controlling for age, sex, and body weight, normal weight Black males had a higher CAVI score in comparison to Hispanic males and White males (5.53±0.15 vs. 5.13±0.15 vs. 5.02±0.15, p=0.04). In univariate analyses, mean BP showed a positive correlation with BMI (r=0.4, p<0.001). Interestingly, BMI had a negative effect on the CAVI score (r= -0.335, p<0.0001). In multivariate analysis, raw BMI and average CAVI scores were significant predictors of the other (R2=0.34, p<0.001, R2=0.21,p<0.001 respectively). No correlation occurred between the CAVI and resting BP values, confirming that CAVI scores were independent of concurrent BP values.

Conclusions:
Significant differences in vascular function exist among ethnic groups. Obese children had lower CAVI scores, suggestive of possible vascular adaptation to obesity in early life. CAVI may be useful measure in long-term intervention studies using diet and exercise, and may be a cost-effective, non-invasive method for examining vascular health in children.
Abstract 19227: Impact of Health Literacy on the Length of Delay in Seeking Care After Worsening of Symptoms in Patients With Heart Failure
Authors: Tsuchihashi-Makaya Miyuki , Matsuoka Shiho
Published: April 2024

Background:
Repeated admissions in patients with heart failure (HF) are related to a delay in responding to HF symptoms. In order to adequately react to HF symptoms, HF knowledge and taking decisions to seek care are essential. Although previous studies have reported that health literacy (HL) was associated with decision making in chronic conditions, little is known on the impact of HL on their behavior for seeking treatment. We analyzed the hypothesis that HL is associated with a delay in seeking care in patients with HF.

Methods:
This cross-sectional study analyzed the data of 112 hospitalized patients with HF (mean age, 69.6 ± 11 years; 68% males; mean left ventricular ejection fraction 49.6 ± 21%). During index hospitalization, a structured interview was conducted to assess the type of worsening HF symptoms and length of delay in seeking care.

Patients completed questionnaires on depressive symptoms and HL (functional, communicative, and critical HL). Clinical and demographic data were also collected. Linear regression analysis was performed to examine whether HL was independently associated with time to seeking care.

Results:
Median patient delay time was 32 h, with 38 patients reporting short delay (<12 h) and 40 patients reporting long delay (>96 h). Patients having a long delay were more likely to be females and have no history of myocardial infarction or HF. Loss of appetite, fatigue, weight gain, and dyspnea on exertion were related to long delay. Levels of communicative and critical HL were associated with long delay (communicative HL short delay, 12.9 vs. long delay, 8.9, P = 0.024; critical HL short delay, 10.2 vs. long delay, 8.0, P = 0.043). After adjusting for confounding factors, communicative and critical HL were shown to be independent predictors of the length of delay in seeking care (communicative HL
β
= –0.176, P =

0.031; critical HL
β
= –0.314, P = 0.033).

Conclusions:
Communicative and critical HL were factors associated with higher risks for delay in seeking care in patients with HF. In order to reduce the delay time, patients with low HL require enhanced education regarding recognition of HF symptoms and the appropriate actions that need to be taken to avoid worsening of symptoms.
Abstract 19229: Effect of Blood Pressure Control on Mortality in Patients With Hypertension - Using the VA National Database
Authors: Fletcher Ross D , Kheirbek Raya , Amdur Richard L. Amdur L , Jones Ronald E , Faselis Charles , Papademetrious Vasalios
Published: April 2024

Medical centers are being presented with an increasing number of hypertensives, and controlling Blood Pressure (BP) has become a healthcare imperative. The outcome of this control can be measured by analysis of mortality. The VA has used an Electronic Health Record with reminders since 1998 to detect and manage hypertension. Vital signs from the entire VA database were analyzed between 2001 and August 2011. Of 8,868,500 patients, 4,353,382 had elevations >140 systolic or >90 on three separate days. BP control was divided into patients who were controlled >66%, 66 to 33%, and <33% of the time.

Mortality improvement varied with age. The mortality decreased in patients with 66% control compared to those with 33% control. This decreased mortality was 10.4% points for those under 70 years old, 13.4% points for 70 - 90 years old, and only .8% for those over 90. The % died was compared between patients with hypertension and those without hypertension in different age groups. The age groups were ≤ 50, 50 - <60, 60 - <70, 70 - <80, 80 - <90 and ≥90. The % point difference between groups and % increase in mortality for patients with hypertension in the ages ≤ 50 was 6.5 - 175%, 50 - <60 was 4.2 - 28%, 60 - <70 was 5.1 - 24%, 70 - <80 was 1.7 - 3.5%, 80 - <90 was .3 - .4%, and for those ≥90 minus .3 - minus .5%. Thus difference in mortality in hypertensive and normotensive groups decreases in higher age groups to the point where a slightly higher percent die in patients without hypertension than with hypertension in patients over 90.

Control of BP over time is associated with decreased mortality in all age groups less than 90. After 90 control of BP has very little effect on mortality. Mortality in hypertensive patients is more than in normotensive patients until 90. When mortality is higher for patients with hypertension than those without, control of hypertension decreases mortality.
Abstract 19434: The Novel PPARalpha-Selective Agonist K-877 Improves Dyslipidemia, Enhances Reverse Cholesterol Transport and Decreases Inflammation and Atherosclerosis
Authors: Hennuyer Nathalie , Duplan Isabelle , Paquet Charlotte , Vanhoutte Jonathan , Touche Véronique , Chinetti Giulia , Lestavel Sophie , Takizawa Toshiaki , Yamazaki Yukiyoshi , Tanabe Sohei , Staels Bart
Published: April 2024

Background:
Atherosclerosis is characterized by lipid accumulation and chronic inflammation in the arterial wall. Elevated levels of apolipoprotein (apo) B-containing lipoproteins are a risk factor for cardiovascular disease (CVD). By contrast, plasma levels of high-density lipoprotein (HDL) and apoA-I are protective against CVD by enhancing HDL functionality and reverse cholesterol transport (RCT). Activation of peroxisome proliferator-activated receptor-alpha (PPARalpha), a ligand-activated transcription factor, controls plasma lipid metabolism, macrophage cholesterol handling as well as the inflammatory response.

Objective:
To study whether pharmacological activation of PPARalpha with the highly potent PPARalpha ligand, K-877, improves lipid metabolism, macrophage cholesterol efflux, inflammation and consequently atherosclerosis development in human apoA-I transgenic mice and in the human apolipoprotein E2 knock-in mouse (apo E2KI) model of mixed dyslipidemia and atherosclerosis.

Methods and results:
In polarized Caco-2/TC7 human intestinal epithelium cells, K-877 treatment decreased apoB secretion and increased the expression of PPARalpha target genes involved in fatty acid oxidation and intestinal HDL production. Moreover, K-877 induced secretion of apoA-I in HDL particles. In primary human macrophages, K-877 promoted macrophage cholesterol efflux to HDL. K-877 treatment of human apoA-I transgenic mice induced plasma HDL cholesterol and apoA-I levels. Moreover, K-877 stimulated in vivo RCT in these mice. In addition, K-877 treatment exerted anti-inflammatory properties in murine and human macrophages. K-877 treatment not only improved the lipid profile, but also reduced inflammatory and macrophage marker gene expression in the aortic crosses as well as aortic atherosclerotic lesion burden in western diet-fed apo E2KI mice.

Conclusion:
These results demonstrate that the novel PPARalpha agonist K-877 exerts beneficial effects on lipid metabolism, RCT and inflammation resulting in anti-atherogenic properties.
Abstract 195: Cardioprotective and Anti-inflammatory Effects of Treatment With Adenocaine/mg2+ in a Porcine Model of Endotoxemia
Authors: Granfeldt Asger , Letson Hayley L , Dobson Geoffrey P , Shi WeiWei , Vinten-Johansen Jakob , Tønnesen Else
Published: April 2024

Introduction:
The combination of adenosine + lidocaine (adenocaine) and Mg2+ (ALM) has demonstrated cardioprotective properties in models of cardiac arrest and hemorrhagic shock, and anti-neutrophil effects in vitro. This study evaluates whether ALM also demonstrates cardioprotective and anti-inflammatory properties in an endotoxemic porcine model.

Methods:
Pigs (37-42kg) received lipopolysaccharide (LPS) at 1 μg/kg/h for 5 hours, and were randomized to: LPS (control) (n=8) or LPS + ALM (n=8). Pigs received a bolus of ALM at start of LPS infusion followed by 4 hours of infusion. Cardiac function was evaluated using pressure-volume loops, and inflammation was assessed by plasma TNF-α and leukocyte superoxide generation.

Results:
Infusion of ALM maintained mean arterial pressure (MAP) at a lower level during the 4 hour infusion period (ALM: 47 ± 1.6 mmHg vs. control: 80 ± 2.9 mmHg, p<0.0001). After discontinuation of ALM, MAP immediately returned to and was maintained at baseline group values (ALM: 89 ± 5 mmHg vs. control: 86 ± 3 mmHg).

The slope of the end-systolic pressure-volume relationship (ESPVR) was unchanged during the experiment in both groups. However, a rightward shift of the volume axis intercept (V0) in the control group indicated decreased contractility; this shift was not observed in the ALM group (control: -0.1 ± 12 ml vs. ALM: -32.5 ± 7.6 ml, p= 0.04). Preload recruitable stroke work (PRSW), an index of overall cardiac performance, decreased in the control group (baseline: 71 ± 4: end: 37 ± 4 mmHg · ml / ml), but was preserved in the ALM group (baseline: 72 ± 5; end: 62 ± 4 mmHg · ml / ml, p<0.001 between groups). Diastolic function evaluated by dP/dtmin (ALM 2221 ± 170 vs. 1793 ± 89 mmHg/sec; p=0.04) and Tau (ALM 36 ± 1.2 vs. 44 ± 2.2 msec; p=0.007) was also significantly improved in the ALM group. Peak TNF-α levels were lower in the ALM group (ALM 7653 ± 1092 vs. 11989 ±1057 pg/ml; p=0.01). While neutrophil superoxide anion release increased by 19 ± 27 % in the control group, it decreased by 74 ± 8% in the ALM group (p=0.0006).

Conclusions:
In this porcine model of endotoxemia, ALM improved cardiac function and reduced the inflammatory response to LPS, thereby extending the beneficial effects of ALM as reported for cardiac surgery, hemorrhagic shock and cardiac arrest.
Abstract 198: Sudden Death While Bathing in Japan
Authors: Suzuki Masaru , Kobayashi Yohsuke , Hori Shingo
Published: April 2024

BACKGROUND:
Japanese people have a unique bathing custom, wherein they immerse themselves in hot water. Many elderly subjects die while bathing, which accounts for an estimated 17,000 deaths annually. The reason for this phenomenon still remains to be elucidated.

OBJECTVE:
The aim of this study was to clarify the recent actual situation of death while bathing.

METHODS:
We investigated the data of all victims for whom the emergency medical system needed to be activated because of accident and/or acute illness in relation to bathing in Tokyo between October 2012 and January 2013. Reports describing each event were obtained from emergency personnel and emergency physicians.

Results:
During the study period, there were 2,630 events in relation to bathing. The number of such events increased as the atmospheric temperature decreased (number of events/mean temperature: October: 383/19.4 Celsius degree; November: 580/12.7; December: 871/ 7.3; January: 796/5.5). Of the 2,630 events, cardiac arrests accounted for 889 events (34%). Of the 889 cardiac arrests, 818 (92%) occurred while the patients bathed in a bathtub filled with hot water. Of the total of 2,630 events, 1,600 (61%) events occurred while the patients were immersed in hot water in their bathtubs (cardiac arrest: 818, trauma: 30, acute illness: 752). Of the 752 patients who became acutely ill while immersed in hot water, 546 needed to be rescued out of the bathtub as they could not get out of the tub by themselves. The major symptoms were lethargy and/or consciousness disturbance. There were a few cases with organic diseases, including cerebrovascular events. Many got better by themselves, without intervention, and did not require in-hospital care.

Discussion:
It was considered that hot water immersion plays a key role in events related to bathing. Many events occurring during bathing, other than cardiac arrest, appeared to be self-limiting conditions. Because hot water immersion easily causes the body temperature to increase, it is possible that events including sudden death, may be related to hyperthermia occurring during hot water immersion.

Acknowledgement:
This study was supported by a Health Labour Sciences Research Grant.
Abstract 201: Beta-Adrenergic Stimulation Promotes Early Electrical Failure During Simulated VF-Induced Cardiac Arrest And Delays Electrical Recovery Upon Reperfusion
Authors: Taylor Tyson G , Garg Vivek , Venable Paul W , Sciuto Katie J , Shibayama Junko , Zaitsev Alexey V
Published: April 2024

During cardiac arrest adrenergic stimulation is enhanced due to both endogenous increase in myocardial tissue catecholamine levels and exogenous epinephrine administration during resuscitation. Whereas alpha-adrenergic stimulation may be beneficial for hemodynamic recovery, there is growing evidence that beta-adrenergic stimulation is detrimental. Clinically, there is controversy as to whether epinephrine administration improves overall survival in cardiac arrest. Here we investigated the effects of beta-adrenergic stimulation on electrical activity during simulated ventricular fibrillation (VF) [[Unable to Display Character: –]] induced cardiac arrest and subsequent reperfusion. We performed optical mapping of the voltage-sensitive dye RH237 in the anterior right and left ventricles (RV and LV) of Langendorff-perfused rabbit hearts subjected to normothermic global no-flow ischemia and rapid pacing (cycle length 200 ms) in the presence or in the absence of isoproterenol (ISO, 30 nM). 2,3-butanedione monoxime (20 mM) was used to reduce motion artifact. Excitable area was measured in optical maps based on the criterion of the minimum time-derivative of the upstroke of the optical action potential. ISO markedly accelerated electrical depression in both LV and RV (more in LV) compared to control hearts (see Figure, * indicate comparisons with significant difference between groups at p<0.05). In addition, ISO delayed recovery of electrical activity upon reperfusion (62±14% recovery in ISO vs.98±2% recovery in control at 5 min of reperfusion, p<0.01). Furthermore, ISO tended to increase the incidence of post-reperfusion arrhythmias compared to control (83% vs. 25%, respectively; p=NS). We conclude that beta-adrenergic stimulation aggravates electrical dysfunction under conditions typically present during cardiac arrest/resuscitation, which might contribute to the overall detrimental outcomes of natural or induced catecholamine increase in this setting.