bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9878: Small Aortic Roots - Clinical Characteristics and Implications for Assessment of Aortic Stenosis in Asymptomatic Patients With Preserved Ejection Fraction
Authors: Bahlmann Edda , Cramariuc Dana , Minners Jan , Ray Simon , Gohlke-Baerwolf Christa , Nienaber Christoph A , Jander Nikolaus , Chambers John B , Kuck Karl-Heinz , Gerdts Eva
Published: April 2024

Background:
The aim was to characterize asymptomatic aortic stenosis (AS) patients with small aortic roots and the implications for assessment of AS severity.

Methods:
We analysed data from 1563 patients with asymptomatic AS enrolled in the Simvastatin Ezetimibe in Aortic Stenosis study. Severe AS was defined by aortic valve area (AVA) as <1.0cm
2
, by AVA indexed for body surface area (AVAI) as <0.6cm
2
/m
2
and by energy loss index (ELI) as <0.6cm
2
/m
2
. Inconsistently graded severe AS was defined as the combination of AVA or ELI <1.0 cm
2
and mean aortic gradient ≤40mmHg.

Results:
A small aortic root (lowest tertile of aortic sinotubular junction diameter, <2.60cm) was present in 32.6% of patients. This group included more women (67.8% vs. 25.0%) and patients with hypertension and patients had smaller body surface area, height and left ventricular (LV) dimensions and higher age and pulse pressure/stroke volume index (PP/SVi) compared to the rest of the study population (all p<0.001). AS severity measured by peak jet velocity or mean gradient did not differ between groups. The prevalence of inconsistently graded severe AS was more common in patients with small aortic roots when using AVA (38.3 vs. 23.5%, p<0.001), but not when using ELI (23.8 vs. 24.0%, p=0.920). In multivariate logistic regression, having small aortic root was associated with a higher prevalence of inconsistently graded severe AS using AVA, independent of female gender, higher PP/SVi and lower height and smaller LV dimensions and wall thickness (Table).

Conclusion:
In asymptomatic AS the use of ELI for grading of AS rather than AVA lowered the prevalence of inconsistently graded severe AS among patients with small aortic roots. However inconsistently graded severe AS remained common using the currently recommended cut-off values for grading of AS. Table. Covariates of small aortic root in multivariate analysis.
Abstract 9958: Enabling of PGC-1 Alpha Signaling by Alpha-lipoic Acid Inhibits and Reverses Vascular Senescence
Authors: Xiong Shiqin , Salazar Gloria , Patrushev Nikolay , Forouzandeh Farshad , Hilenski Lula , Alexander R. W
Published: April 2024

Vascular senescence has been implicated in atherosclerotic arterial disease clinically and in animals. Senescence induction conditions include telomere and mitochondrial dysfunction, DNA damage, and elevated oxidative stress. Alpha-lipoic acid (ALA) is a powerful natural antioxidant, implying a potential important role of ALA in senescence pathogenesis. We showed recently peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a primary negative regulator of vascular senescence. We thus posited that ALA may inhibit vascular senescence via enabling PGC-1 alpha signaling networks. We generated a PGC-1 alpha and ApoE double knockout mouse model and show that mice with PGC-1 alpha deficiency develop a senescence phenotype (2.25 fold) that is associated with increased cellular general ROS levels (3 fold) and mitochondrial superoxide production (2 fold). We demonstrate that ALA (100 μM for in vitro, 10 mg/kg/d for in vivo experiments) upregulates expression of PGC-1 alpha and PGC-1 alpha-dependent downstream ROS defense molecules, including SIRT1, catalase, MnSOD, heme oxygenase 1 (HO-1), and its mitochondrial targets including NRF-1 and 2, and TFAM, while decreases expression of the senescence marker p53 in mice aortas and vascular smooth muscle cells (VSMC). The upregulation of the endogenous antioxidants and mitochondrial targets is prevented by PGC-1 alpha deficiency. Further, ALA (100 μM) is sufficient to inhibit and reverse VSMC senescence through a blockade of PGC-1 alpha acetylation, thus preventing the downregulation of SIRT1 and catalase triggered by angiotensin II (Ang II), a major hormonal inducer of vascular senescence. Moreover, ALA inhibits Ang II-induced cellular ROS and mitochondrial superoxide production, both of which are abolished in the absence of PGC-1 alpha. Our findings show that ALA is an important activator of PGC-1 alpha signaling pathways and unravel a previously unappreciated role for ALA in mitigating oxidative stress-dependent vascular senescence via PGC-1 alpha. These observations support the notion that enabling of PGC-1 alpha signaling network might be a promising strategy in the development of intervention for oxidative stress-dependent, age-related, chronic diseases.
Abstract 10035: Oesophageal Heat Exchangers With a Diameter of 11mm or 14,7mm are Equally Effective for Conduction of Mild Therapeutic Hypothermia
Authors: Schroeder Daniel C , Guschlbauer Maria , Maul Alexandra , Finke Simon R , Paal Peter , Padosch Stephan A , Wetsch Wolfgang A , Böttiger Bernd W , Sterner-Kock Anja , Herff Holger
Published: April 2024

Introduction:
Induction of mild therapeutic hypothermia (MTH) is recommended for adult patients after out-of-hospital-cardiac-arrest (OHCA) [1]. Conventional surface cooling methods are simple to apply, but reveal inaccuracy during maintenance of MTH and are accompanied by more adverse events [2]. Internal cooling with an endovascular cooling device (ECD) is effective and reliable during maintenance of MTH, but is difficult to apply. Since the esophagus is located adjacent to the heart, aorta and inferior cava vein fast temperature conduction from and to the blood-stream could be achieved by use of a semi-invasive esophageal heat exchanger (EHE) that can be inserted easily and safely.

Hypothesis:
MTH can be conducted accurately, effectively, safely and without esophageal tissue damage with a newly developed EHE in pigs.

Methods:
Sixteen pigs (28.8±0.6kg) were randomly assigned to an EHE of 11mm (n=8) or 14.7mm (n=8) diameter. After induction of anesthesia, EHE were blindly inserted and connected to a chiller (HICO Variotherm 555, Hirtz & Co.KG, Cologne, Germany). Via the EHE, pigs were cooled to a target temperature of 33°C, maintained at 33°C for 1 hour, then covered with a silver-blanket and rewarmed with a rate of 0,25°C/h. After 10h of rewarming esophagi including larynx and cardia were resected in their entire lengths and analyzed by means of histopathology. Pulmonary artery temperature was recorded continuously.

Results:
Mean cooling rates were 2.8±0.1°C/h (11mm) and 2.9±0.1°C/h (14.7mm) (p=0.41). Average deviations from target temperature during maintenance were 0.1±0°C in both groups (p=0.44). Rewarming rates were 0.17±0.03°C/h (11mm) and 0.19±0.02°C/h (14.7mm) (p=0.65). Occasional mild diffuse mononuclear acute inflammatory transepithelial infiltrates were found in the laryngeal region, but not in the esophagus.

Conclusions:
Use of the EHE for MTH in pigs seemed to be efficient, safe and reliable.

References:
[1] Bernard,S.A., et al.,
Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia.
N Engl J Med, 2002.
346
(8) [2] Oh, S.H.et al.,
An observational study of surface versus endovascular cooling techniques in cardiac arrest patients: a propensity-matched analysis.
Crit Care, 2015.
Abstract 10110: Effects of Inorganic Nitrate on Endothelial Dysfunction Induced by Periodontitis
Authors: Fernandes Daniel , Khambata Rayomand , Ahluwalia Amrita
Published: April 2024

Introduction:
Evidence supports an association between periodontal disease and cardiovascular disease (CVD) risk. Periodontal disease is thought to cause vascular dysfunction contributing to atherogenesis and resulting in an increased risk of stroke and coronary heart disease. Safe therapeutics that might improve vascular function in such patients to reduce risk of CVD is a current unmet need. It is thought that a critical step in the increased CVD risk relates to a periodontitis-induced endothelial dysfunction. Evidence suggests that the intervention of dietary nitrate, to elevate circulating nitrite levels, improves endothelial function. We investigated whether dietary nitrate might provide a method for prevention or reversal of the endothelial dysfunction induced by periodontitis.

Methods:
Male C57BL6 mice were either untreated or randomly assigned to receive KNO3 or KCl (15 mmol/L; in the drinking water) either 7 days prior or 7 days post ligature placement (periodontitis) or a sham procedure. After 14 days blood samples were collected for assessment of circulating cell types and activation state using flow cytometry. The vasoreactivity of aortic rings were assessed ex vivo. Maxillae were removed for alveolar bone loss measurement.

Results:
When compared to sham animals, ligature-induced periodontitis resulted in bone loss (~2-fold increase in the distance cement enamel junction and the alveolar crest, p<0.001, n=9). This was associated with neutrophilia (n=9, P<0.05) and endothelial dysfunction, reflected by a reduction of acetylcholine-induced relaxation (~20% suppression of the Max response, p<0.05, n=5). Vascular responses to the endothelium-independent vasorelaxant, spermine NONOate, were unchanged. Dietary nitrate treatment improved endothelial function when given either as prophylaxis (p<0.01, n=5) or reversal therapy (p<0.01, n=5). These improvements were not associated with any changes in ligature-induced bone loss but were associated with reduced numbers and activation of circulating neutrophils.

Conclusion:
Dietary nitrate improves vascular function in periodontitis in mice and thus may represent an alternative treatment in the cardiovascular complications associated with this condition.
Abstract 10208: Differences in Natriuretic Peptide Levels by Race/Ethnicity in the Multi-Ethnic Study of Atherosclerosis
Authors: Gupta Deepak K , Daniels Lori B , Cheng Susan , DeFilippi Christoper , Criqui Michael H , Maisel Alan , Lima Joao A , Bahrami Hossein , Greenland Phillip , Cushman Mary , Tracy Russell , Siscovick David , Bertoni Alain , Carr J. Jeffrey , Wang Thomas J
Published: April 2024

Introduction:
Natriuretic peptides (NP) are cardiac-derived hormones with favorable cardio-metabolic actions including natriuresis, diuresis, and vasodilation. Low NP levels have been associated with increased risks of hypertension and diabetes, conditions with variable prevalence by race/ethnicity. Heritable factors underlie a significant proportion of the inter-individual variation in NP levels, but the specific influence of ancestry is unknown.

Methods:
In 4,162 individuals (40% White, 24% Black, 23% Hispanic, and 13% Chinese) without prevalent cardiovascular disease at baseline (2000-2002) in the Multi-Ethnic Study of Atherosclerosis, multivariable adjusted linear regression and restricted cubic splines were used to examine differences in serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels according to self-reported race/ethnicity or ancestry determined from genetic ancestry informative markers.

Results:
NT-proBNP levels were significantly lower in Black and Chinese individuals than in White individuals, and were intermediate in Hispanics (Figure 1). Self-identified Blacks and Hispanics were the most genetically admixed groups. Among individuals self-identified as Black, a 1 standard deviation (14%) increase in genetic European ancestry was associated with 8% higher (95%CI, 1 to 16%) NT-proBNP. Among Hispanic individuals, genetic European ancestry was also positively associated with NT-proBNP levels, while African ancestry was negatively associated with NT-proBNP (Figure 2).

Conclusions:
NP levels differ substantially according to race/ethnicity, with the lowest levels among Black and Chinese individuals. Racial/ethnic differences in NP levels appear to have a genetic basis, with European and African ancestry associated with higher and lower NT-proBNP levels, respectively. Relatively low NP levels may, in part, contribute to racial/ethnic disparities in cardio-metabolic disease susceptibility.
Abstract 10337: Using Landiolol During Primary Percutaneous Coronary Intervention Attenuates Myocardial Reperfusion Injury in Patients With ST-segment Elevation Acute Myocardial Infarction
Authors: Kiyokuni Masayoshi , Mitsuhashi Takayuki , Sugano Teruyasu , Endo Tsutomu , Ishigami Tomoaki , Ishikawa Toshiyuki , Umemura Satoshi , Kiyokuni Kazuo
Published: April 2024

Introduction:
Landiolol is the beta-1 selective receptor blocker and its half-life elimination is 4 minutes. The safety and efficacy of landiolol started before coronary reperfusion in patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) remains unclear. We assessed the hypothesis that early use of landiolol promotes optimal reperfusion without increasing adverse events for those patients.

Methods:
We recruited 220 consecutive patients with STEMI performed pPCI. Patients with heart rate<50, Killip class≧2, old myocardial infarction and 2 or 3 degree of AV-block on admission were excluded. 60 patients were non-landiolol group with conventional treatment admitted from October 2010 to September 2012. 55 patients were landiolol group admitted from October 2012 to September 2014. Administration of landiolol was started before pPCI with 3 μg/kg/min and stopped within 12 hours when oral beta-blockers were administered. ST-segment resolution (STR) was defined as more than 70% resolution of sum of ST-segment elevation at the J point between at the time of admission and just after pPCI.

Result:
Time form admission to stating landiolol was 35±23min in landiolol group. Age, sex, coronary risk factors, culprit lesion, SYNTAX score (19±10vs18±10) and reperfusion time did not differ between the two groups (all NS). The rate of non-sustained ventricular tachycardia (27vs50%, p=0.013), worsening heart failure (0vs8%, p=0.029) and shock (15vs31%, p=0.030) within 12 hours after the admission was lower in landiolol group. Although, at the time of finishing pPCI, systric blood pressure did not differ between the two groups (117±21vs124±24mmHg, p=0.09), heart rate was lower (66±11vs77±14/min, p<0.01) and the rate of STR was higher (61vs42%, p=0.023) in landiolol group. Multivariate analysis showed that landiolol use was an independent predictor of STR (OR2.51, p=0.045). Within 6 months after the admission, the rate of worsening heart failure (0vs7%, p=0.07), target vessel revasculization (5vs10%, p=0.17) was lower in landiolol group.

Conclusion:
In low risk patients with STEMI, using landiolol during pPCI may attenuate myocardial reperfusion injury and reduce adverse events.
Abstract 10464: Are Adolescents Meeting the 2020 Goals of the American Heart Association for Ideal Cardiovascular Health?
Authors: Sundaresan Shyamala , Pratt Charlotte A , Iannotti Ronald J , Haynie Denise , Li Kaigang , Simons-Morton Bruce
Published: April 2024

Introduction:
There are limited data on whether adolescents meet the 7 metrics of the American Heart Association’s ideal cardiovascular health (ICVH), and relations between ICVH and demographic characteristics. The behavioral metrics (ICVH-B) are: never tried/never smoked; normal BMI (≤85th percentile); physical activity (PA) ≥ 60 min daily; and consuming a healthy diet (4-5 components).The ICVH physiological metrics are: blood pressure (BP) <90th percentile; total blood cholesterol (TBC) <170 mg/dl; and fasting blood glucose (FBG) <100 mg/dl.

Methods:
We assessed the four ICVH-B in the NEXT Generation Health Study (NEXT), a nationally represented cohort of U.S. 10
th
graders (N= 2,734, 16.24±0.53 years). NEXT participants were categorized as ideal (met 4 metrics), intermediate (met 2-3), or poor (met 0-1). All 7 metrics were assessed in NEXT Plus, an intensively measured sub-sample of NEXT (n=278 overweight, n=282 normal weight). NEXT Plus participants’ ICVH was categorized into ideal (≥5 metrics), intermediate (2-4 metrics) or poor (0-1 metrics).

Results:
Of the NEXT adolescents, 0.4% met ICVH-B criteria for ideal, 26% for intermediate, and 72% for poor health. Nonsmoking was the most (85%) and healthy diet the least (23%) prevalent metric. ICVH-B prevalence estimates did not differ significantly by race/ethnicity or family affluence. Of the NEXT Plus students, 0.2% met all 7 ICVH metrics; 28% were categorized as ideal, 71% as intermediate and 1% as poor. Regarding the behavioral metrics, 51% were of normal weight by design, 85% were nonsmokers, 26% met PA criteria, and 39% reported a healthy diet; most met the physiological metrics, 96% for BP, 76% for TBC, and 53% for FBG.

Conclusion:
Few U.S. adolescents met the ideal cardiovascular health metric. Notably, the two metrics least likely to be met were behavioral, and herefore potentially modifiable through intervention at the individual, family,environment and policy levels.
Abstract 10819: Prognostic Value of Coronary Artery Calcium Score in Acute Chest Pain Patients Without Known Coronary Artery Disease in Emergency Department: Systematic Review and Meta-analysis
Authors: Chaikriangkrai Kongkiat , Ungprasert Patompong , Jhun Hye Yeon , Nabi Faisal , Mahmarian John , Chang Su Min
Published: April 2024

Backgrounds:
Role of coronary artery calcium score (CACS) in acute chest pain patients is currently not well defined. The objective of this study was to investigate the prognostic value of CACS obtained by noncontrast electrocardiogram-gated CT in acute chest pain patients suspected for cardiac origin in emergency department.

Methods:
We search Pubmed, Embase, Cochrane databases for longitudinal studies of CACS in acute chest pain patients without known coronary artery disease (CAD) in emergency department which reported major adverse cardiovascular events (MACE), consisting of death, nonfatal myocardial infarction (NFMI), revascularization or stroke. Pooled annualized event rate, risk ratios and 95% confidence intervals (CI) were analyzed. A random-effect, generic inverse variance model was used.

Result:
Eight studies evaluated 3556 patients (mean age = 51 years, 47% men) with the pooled prevalence of hypertension, diabetes mellitus, dyslipidemia and smoking of 42%, 16%, 33% and 33% respectively. During a median follow-up of 5 months (range 1-60 months, 37234 patient-months), the overall pooled MACE rate was 7.6%/y. The pooled event rate of MACE for CACS=0 versus CACS>0 was 0.8%/y (13 events in 18874 patient-months) versus 14.6%/y (224 events in 18360 patient-months). The pooled risk ratio with CACS=0 was 0.04 (95% CI: 0.02-0.07, p<0.001) for MACE compared to CACS>0. The sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio of CACS for MACE was 94.5%, 64.1%, 15.8%, 99.4%, 2.63 and 0.09 respectively. The heterogeneity among studies was low with an I
2
of 13%.

Conclusion:
In acute-chest-pain patients without known CAD presenting to emergency department, MACE was rare in those with CACS=0. Zero CACS by noncontrast electrocardiogram-gated CT in this population has high negative predictive value (>99%) for subsequent cardiac events.
Abstract 10824: A Novel Role of Endothelial Autophagy in the Regulation of Thrombosis
in vivo
Authors: Yau Jonathan W , Hou Yan , Lei Xi , Ramadan Azza , Teoh Hwee , Quan Adrian , Singh Krishna K , Al-Omran Mohammed , Ni Heyu , Verma Subodh
Published: April 2024

Background:
Arterial thrombosis of native and graft vessels is the inciting event for acute coronary syndromes, and the cause of significant cardiovascular morbidity and mortality. Endothelial cell (EC) dysfunction is believed to play a central role in the pathobiology of thrombosis. ECs are activated upon atherosclerotic plaque rupture and induce the expression of tissue factor (TF) with resultant atherothrombotic sequelae. The molecular basis of how endothelial TF is unregulated remains unknown. We hypothesize that endothelial autophagy, a process involved in cellular homeostasis and stress responses, plays a causal role in the expression of TF, and via this mechanism modulates thrombosis.

Methods:
We generated EC-specific
ATG7
knockout (EC-ATG7
-/-
) mice using CreLoxP technology. We used small interfering RNA (siRNA) to knockdown and characterize the effect of
ATG7
inhibition in HUVECs. We also employed intravital microscopy in FeCl
3
-induced carotid and laser-induced cremaster artery injury to evaluate thrombosis.

Results:
siRNA-mediated knockdown of
ATG7
in HUVEC resulted in decreased TF mRNA and protein expression by over 60% (N=3-5; p<0.05). Mean TF mRNA level in EC-ATG7
-/-
mice was 43% lower (p<0.05) compared with WT mice, after FeCl
3
-induced carotid artery injury. Time to carotid artery occlusion was significantly prolonged in EC-ATG7
-/-
mice compared with WT mice (15.5±2.0 and 31.0±4.0 min, respectively; N=10/group; p=0.003). The time to maximum platelet fluorescence intensity in EC-ATG7
-/-
mice was significantly prolonged relative to that for WT mice (1.0±0.6 and 2.3±1.2 min, respectively; N=33-38 thrombi; p<0.0001). Thrombi size, as determined by platelet fluorescence intensity, were significantly smaller in EC-ATG7
-/-
vs. WT mice, (1.8±0.7 and 8.2±2.9, respectively; x10
9
; p=0.049).

Conclusions:
Knockdown of ATG7 resulted in reduced TF expression in vitro and in vivo. Compared to WT mice, EC-ATG7
-/-
mice exhibited 2-fold greater occlusion times and reduced thrombi formation across all models of thrombosis. Taken together, these findings are evidence that endothelial autophagy regulates thrombosis in a TF-dependent manner, and underscores a novel and previously unrecognized target for antithrombotic drug development.
Abstract 11132: Post-traumatic Stress Disorder is a Marker of Worse Endothelial Function
Authors: Grenon Marlene , Owens Christopher , Gasper Warren , Alley Hugh , Perez Sandra , Whooley Mary , Neylan Thomas , Cohen Beth
Published: April 2024

Introduction:
Current knowledge supports significant associations between stressful life events including post-traumatic stress disorder (PTSD) and increases in cardiovascular disease (CVD) and mortality. Despite strong evidence supporting the association of PTSD and CVD, the underlying mechanisms remain poorly understood.

Hypothesis:
We hypothesized that patients with PTSD would demonstrate endothelial dysfunction, a key factor in the development and progression of CVD.

Methods:
Two hundred sixty one outpatients treated at the Veterans Affairs Medical Center (VAMC) underwent endothelial function (EF) testing as part of the OMEGA-PAD Study or the Mind Your Heart Study. Flow-mediated brachial artery vasodilation (FMD) was performed to assess EF and current PTSD symptoms were assessed with the PTSD Checklist for DSM-IV. Multivariate linear regression models were used to determine the association between PTSD and FMD.

Results:
Patients with PTSD (n=69) had a significantly lower brachial artery FMD (6.2 ± 3.4% vs 7.4 ± 3.8%; p=0.03). They also had higher systolic blood pressure (p=0.04), diastolic blood pressure (p=0.01) but were also less likely to be on an ace inhibitor (p=0.04) or a beta-blocker (p=0.05) (See Table). Furthermore, patients with PTSD were more likely to have depressive symptoms (p=<0.0001). Univariate analysis demonstrated that PTSD (p=0.02), age (p=0.04), renal function as measured by eGFR (p=0.02), and hypertension (p=0.009) were associated with FMD. After adjusting for these factors, PTSD remained significantly associated with worse EF (coefficient -1.62, CI -2.93, -0.31, p=0.02).

Conclusions:
PTSD is associated with worse EF in an outpatient population treated at the VAMC San Francisco. Since current literature supports a heightened risk of CVD with a decrease in FMD, our data suggest that treatment of mental health issues has the potential to improve vascular function and subsequently the morbid burden of CVD.
Abstract 11496: Differences in Bystander Cardiopulmonary Resuscitation and First Responder Defibrillation Narrowed to Similar Levels in Urban and Non-urban Out-of-Hospital Cardiac Arrest Patients Following a Quality Improvement Program in North Carolina
Authors: Kragholm Kristian , Malta Hansen Carolina , Dupre Matthew , Strauss Benjamin , Tyson Clark , Monk Lisa , Pearson David , Nelson R. Darrell , Fosbol Emil L. , Anderson Monique , Jollis James G. , Rea Thomas , McNally Bryan , Granger Christopher B.
Published: April 2024

Introduction:
Differences in care and outcomes between non-urban versus urban out-of-hospital cardiac arrest cases have previously been shown. Therefore, we examined temporal changes in bystander and first responder interventions, direct transport to PCI center and outcomes in non-urban versus urban arrests during Heart Rescue initiatives to improve regional systems of care and outcomes during 2010-2014 in North Carolina.

Hypothesis:
Differences in bystander and first responder interventions, direct transport to PCI center, and outcomes have narrowed over time between non-urban and urban cases.

Methods:
From the Cardiac Arrest Registry to Enhance Survival, we identified non-emergency medical service witnessed cases from 16 counties (catchment population 3,143,809) in North Carolina with complete case capture during 2010-2014. We used geospatial information on arrest location and US Census classification to categorize urban areas with ≥50,000 versus non-urban with <50,000 people.

Results:
Of 7,885 patients, 21.1% of the arrests (n=1667) occurred in non-urban areas and 78.9% (n=6218) occurred in urban areas. Bystander cardiopulmonary resuscitation (CPR), first responder defibrillation and outcomes improved in both groups, but most substantially in non-urban cases (Figure). Overall, bystander defibrillation was 2.9% in non-urban versus 8% in urban cases (P<0.01) and did not change over time. Similarly, no change was seen over time in proportion taken directly to PCI centers (overall 54.2% versus 97.4%, respectively).

Conclusions:
Differences in bystander CPR and first responder defibrillation substantially narrowed to similar levels between non-urban and urban cases following Heart Rescue quality improvement program during 2010-2014 in North Carolina. Significant differences in bystander defibrillation and direct transport to PCI center remained and represent future target areas to potentially further reduce differences in outcomes.
Abstract 11579: Myocardial Infarction Size by 3D Reconstruction of Late Gadolinium Enhanced Magnetic Resonance Cardiac Imaging in the Mouse: Correlation With Left Ventricular (LV) Global and Regional Performance
Authors: Chao Chieh-Ju , Gu Yusu , Bussell Robert , Bradford William , Hoshijima Masahiko , Peterson Kirk L
Published: April 2024

Background:
Assessment
in vivo
of murine myocardial infarction (MI) size, and its correlation with global and regional LV dysfunction, remains problematic. In this experimental MI model, the validity of 3-D reconstruction of late gadolinium enhanced (LGE) Bruker Biospec 7T magnetic resonance (MR) images was tested and compared to degree of LV dysfunction.

Methods and Results:
Thirty-three male C57BL/6J mice were studied (Figure 1A). LGE MR images were obtained by FLASH-cine pulse sequence.
Continuity 6
software was used to 3D reconstruct the LV from 1.0 mm contiguous 2D slices at end-diastole (Figure 1B) and -systole; wall motion was quantitated by 3D % shrinkage and regional surface area change (RSAC) at the endocardium. Hemodynamic assessment was followed post-mortem by histologic (TTC) measurement of infarction size. In the chronic MI study, control measurements were used for normalization of 3D parameters. Results are shown in Table 1. We found highly significant negative linear correlations between the absolute increase of max dP/dt, by dobutamine stimulation and LGE MI size at 2 days after MI in the acute (r=-0.83, P<0.0001) and at 4 weeks in the chronic MI (r=-0.77, P=0.0052) groups. 3D % RSAC measured at 2 days precisely predicted the ESV at 4 weeks (r=0.95, P<0.0001).

Conclusion:
3D reconstruction of LGE MR images quantitates MI size that correlates significantly with histologic infarct size, regional impairment of 3D shortening, endocardial surface area change, and LV global contractile reserve. This approach provides accurate end-points for interventions, pharmacologic and genomic, that potentially limit both direct and reperfusion injuries associated with acute MI.
Abstract 11735: Periprocedural Cerebral Ischemic Events With TAVI Performed Without Prior Balloon Dilatation of the Aortic Valve: A Randomized Prospective Study
Authors: Leclercq Florence , Labour Jessica , Menjot de Champfleur Nicolas , Macia Jean Christophe , Lattuca Benoit , Schmutz Laurent , Gervasoni Richard , Agullo Audrey , Vernhet Helene , Cayla Guillaume
Published: April 2024

Introduction:
Balloon aortic valvuloplasty (BAV) is considered as an essential part of Transcatheter Aortic Valve Implantation (TAVI) procedure, but cerebral embolization may occur during this step.

Hypothesis:
We assessed the hypothesis that TAVI performed without prior BAV may be associated with decrease of risk of periprocedural cerebral ischemia assessed using diffusion-weighted (DW) magnetic resonance imaging (MRI).

Methods:
In this prospective monocentric study we randomized consecutive patients who underwent TAVI with the new generation balloon expandable SAPIEN 3 prosthesis. Group 1 (n=14) included patients with BAV performed prior implantation of the prosthesis and group 2 (n=14) patients with direct implantation of the valve. Periprocedural cerebral ischemia was assessed blindly by neurological testing and serial cerebral DW MRI at baseline and within 3 days after TAVI.

Results:
On the 28 patients included, mean age was 83 years (78-86),18 were of female gender (64.3%) and mean logistic Euroscore II was 8.4 (6.3-10.6) without significant differences between the 2 groups. Implantation of the valve was successful in all patients. Considering the total population, preexisting silent ischemic brain abnormalities were observed in 11 patients (39.3%) and microbleeds in 14 patients (50 %). New foci of restricted diffusion, mainly lacunar, and new microbleeds were found on cerebral DW MRI in respectively 13 (46.4%) and 6 (21%) patients after the procedure without significant difference between the 2 groups (table 1). There were neither apparent impairments of neurocognitive function or neurological events during the in-hospital stay in the 2 groups.

In conclusion: Direct implantation of new generation balloon expandable prosthesis appears feasible but is not associated with reduction of periprocedural ischemic cerebral events . These results argue for embolization occurring during positioning of the valve rather than during balloon valvuloplasty.
Abstract 11753: Disjunction of the Mitral Annulus Is Associated With Paradoxical Systolic Expansion and Flattening in Degenerative Mitral Valve Disease: A Real-time 3-dimensional Transesophageal Echocardiographic Study
Authors: Lee Alex P , Jin Chun-na , Underwood Malcolm J , Wong Randolph , Tang Zhe , Fan Karen Yi-ting , Sun Jing-ping , Song Wan
Published: April 2024

Introduction:
Disjunction of the mitral annulus, defined as a separation between the atrial wall-mitral valve junction and the left ventricular attachment, is commonly seen on echocardiography in patients with degenerative mitral valve prolapse (MVP). Few data exists on the three-dimensional (3D) geometry of annular disjunction and its relationship with the annular dynamic function.

Hypothesis:
We assessed the hypothesis that annular disjunction is associated with abnormal annulus structure and function.

Methods:
A total of 138 subjects including 108 MVP patients (58±11years) and 30 subjects with normal MV (57±15years) were studied using real-time 3D transesophageal echocardiography. The annular circumference was examined in multiple radial planes at 10° intervals for any disjunction. The location, separation distance, and circumferential extent of disjunction were assessed. The annular area, width, and height were measured at end-diastole and end-systole.

Results:
Annular disjunction was evident in 61 (56%) MVP patients and 3 (10%) normal subjects (P<0.0001). Among MVP patients, disjunction is usually located adjacent to the prolapsed segments, circumferentially spanning over 79°±42° (20° to 190°) of the annulus, with the maximal separation measuring 8.7±3.8mm. Annular disjunction is associated with more prolapsed segment (2.0±1.6 vs 1.3±0.6, P=0.0021), more severe mitral regurgitation (effective regurgitant orifice area=0.64±0.49 vs 0.45±0.23cm
2
, P<0.0001), paradoxical systolic increase in annular area and decrease in height-to-commissural width ratio (AHCWR) (Figure), despite normal ventricular ejection fraction (62±5% vs 62±7%, P=0.97).

Conclusions:
Mitral annular disjunction is associated with decoupling of annular and ventricular function leading to paradoxical annular expansion and flattening of the annular saddle-shape during systole in patients with MVP and may require specific surgical correction.
Abstract 11908: Osteoprotegerin and Myocardial Fibrosis in Patients With Aortic Stenosis
Authors: Vassiliou Vassilis , Raphael Claire E , Malley Tamir , Aggarwal Nikhil , Selvendran Subothini , Berry Helen , Donovan Jackie , Nyktari Eva , Auger Dominique , Pennell Dudley J , Prasad Sanjay K
Published: April 2024

Introduction:
Understanding the mechanistic role of valve calcification and myocardial fibrosis in patients with aortic stenosis (AS) remains challenging. Osteoprotegerin (OPG), a member of the TNF receptor family, is known to mediate valve calcification in AS; however its role on myocardial fibrosis has not been evaluated.

Hypothesis:
We hypothesized that OPG stimulates common pathways for valve calcification and myocardial fibrosis and investigated the association of OPG and presence of myocardial fibrosis.

Methods:
Between 2011 and 2015, consecutive consenting patients with moderate (1.0-1.5cm2) or severe (<1cm2) AS who had cardiovascular magnetic resonance (CMR) with late gadolinium enhancement were included. CMR parameters were analysed by blinded observers and patients characterized into 3 groups according to the pattern of fibrosis: presence of midwall fibrosis, presence of chronic infarction or absence of fibrosis. OPG levels were measured using ELISA and compared between the 3 groups.

Results:
113 patients (76±10 years, 78 male) were included. 37 patients had no fibrosis, 40 patients had midwall fibrosis and 34 had chronic infarction. Max OPG level was 23.01 pmol/, min 2.22 pmol/L and mean 7.24± 3.45pmol/L. OPG per group was: no fibrosis= 6.29 pmol/L, midwall fibrosis=7.13 pmol/L and chronic infarction=8.42 pmol/L. There was no association between OPG level and presence of midwall fibrosis compared to no fibrosis (p=0.114). However, patients with chronic myocardial infarction had higher OPG than patients with no fibrosis (p=0.007).

Conclusions:
OPG is known to promote valve calcification in patients with AS. This is the first study to demonstrate that there is no association between the level of OPG and presence of myocardial midwall fibrosis. However higher OPG was observed in patients with chronic ischemia when compared to patients with no fibrosis.
Abstract 11931: Plasma Metabolite Profiling in Heart Failure Patients: Risk Association and Heritability
Authors: Lanfear David , Levin Albert , Li Jia , She Ruicong , Wang Yun , Williams L. Keoki , Gardell Stephen , Sabbah Hani
Published: April 2024

Background:
Metabolite profiling can unveil biomarker signatures for health and disease. We tested whether the plasma metabolite profile in heart failure (HF) patients could predict survival independent of established factors, and whether the metabolite levels are heritable.

Methods:
Patients (n=400) who met Framingham criteria for HF were included. Fasting blood samples were obtained, and DNA and plasma isolated and stored at -70
o
C. Amino acids, organic acids, and acyl carnitines were quantified using mass spectrometry. Genome wide genotyping was also performed. Association of metabolites with survival was tested using lasso penalized Cox regression; a resulting multi-metabolite risk score (MRS) was tested in 10-fold cross validation using time-dependent ROC curves. We retested the MRS in Cox models adjusted for conventional covariates (age, gender, race, ejection fraction (EF), CAD, COPD, creatinine, atrial fibrillation, stroke, NTproBNP). We estimated heritability of the MRS components using genome-wide data, calculated separately in African Americans and whites.

Results:
The cohort was 50% African American, 50% female, 67% low EF, and mean age 70 y. In cross-validation the MRS had AUC of 0.705 and 0.658 at 1 and 5 years, respectively. Dichotomized MRS was associated with a 4.5 fold risk of death (FDR=1.49x10
-8
, Figure). When added to a conventional risk model, the MRS still carried a HR of 2.6 (p=2.38 x 10
-4
). Among 14 MRS analytes, 4 had heritability estimates >20% in each race group (Table).

Conclusion:
Plasma metabolite profile is an independent predictor of survival among HF patients, and risk-associated metabolite levels may be heritable. Validation is needed.
Abstract 12030: The Process of Left Atrial Appendage Dysfunction Evaluated by 3D Transesophageal Echocardiography
Authors: Haruka Fujimaki , Hama Yoshiyuki , Sekine Tai , Fujimoto Yoshihide , Yamamoto Masashi , Himi Toshihide
Published: April 2024

Introduction:
Left atrial appendage (LAA) dysfunction progressively evolves in atrial fibrillation (AF) patients. LAA transesophageal echocardiographic (TEE) parameters can predict thrombotic tendencies and AF treatment outcomes. However, the process of LAA dysfunction remains to be elucidated.

Methods:
Eighty-four persistent AF patients (64men, age 68±10) that underwent TEE were enrolled. We obtained three-dimensional full-volume LAA data from these patients and reconstructed two-dimensional LAA cross sectional images at the orifice and mid-portion level of the LAA. The maximum and minimum cross-sectional LAA areas were measured at each position and the area change ratio at the orifice (ACR-O) and mid-portion (ACR-M) were calculated. We defined low contractility as a decreasing area change ratio (ACR) of <30% at each position and evaluated the associations between the ACR-O, ACR-M, and continuous AF duration.

Results:
The patients were categorized into three groups based on the ACR-O and ACR-M: those that maintained both ACR-Os and ACR-Ms (n=48, Group 1), those with reduced ACR-Os and maintained ACR-Ms (n=17, Group 2), and those with both reduced ACR-Os and ACR-Ms (n=19, Group 3). There were no patients with maintained ACR-Os and reduced ACR-Ms.

The mean continuous AF durations of each group were 29±42, 54±40, and 88±87 months, respectively. In Group 3, the LAA emptying flow velocity was significantly decreased compared to that in Group 1 and Group 2 (38±19, 31±14, 22±11,cm/s) and LAA thrombi were detected more frequently (0%, 12%, 58%).

Conclusions:
This study suggested that LAA dysfunction occurred from the orifice and progressed toward the mid-portion. When LAA dysfunction extended over the mid-portion, the LAA flow velocity decreased and LAA thrombi were detected more frequently. Even though anticoagulant drugs were administrated in all patients, 58% of patients had thrombi in Group 3. These patients should be considered for additional therapeutic approaches.
Abstract 12170: Paced-QRS fragmentation as a Novel Predictor for Ventricular Fibrillation in Patients With Brugada Syndrome
Authors: Kataoka Naoya , Mizumaki Koichi , Tuzino Yasushi , Nakatani Yosuke , Sakamoto Tamotsu , Nishida Kunihiro , Inoue Hiroshi
Published: April 2024

Introduction:
In patients with Brugada syndrome, conduction abnormalities could serve as a substrate for ventricular fibrillation (VF) and fragmented QRS appears to be a predictor of VF.

Hypothesis:
Therefore, we hypothesized that right ventricular apical pacing (RVP) could enhance or unmask the QRS fragmentation in the right precordial leads and paced-QRS fragmentation might predict a risk of VF in patients with Brugada syndrome.

Methods:
Eighteen consecutive male patients who underwent ICD implantation were categorized into 10 patients with spontaneous VF (group VF(+)) and 8 patients without VF (group VF(-)). The number of spikes within the QRS complex in leads V1-V2 and the duration of QRS fragmentation in lead V1 were evaluated (with 0.05-150 Hz filters) during both sinus rhythm (SR) and during RVP using ICD at VVI 80 bpm or 110 bpm.

Results:
Sum of spikes in lead V1-V2 was not significantly different between groups VF(+) and VF(-) during SR; however, it was greater in VF(+) than VF(-) during RVP at VVI 80 bpm (7.0±2.8 vs 2.9±5.2, p = 0.04) and VVI 110 bpm (10.7±3.7 vs 2.4±3.2, p = 0.01). The duration of QRS fragmentation in lead V1 was longer in VF(+) than VF(-) at VVI 110 bpm (173±32 ms vs 45±44 ms, p = 0.006). In VF(+), sum of spikes (V1-V2) was higher and the duration of QRS fragmentation (V1) was longer at VVI 110 bpm compared to VVI 80 bpm (10.1±3.7 vs 7.0±2.8, p = 0.02 and 173±32 ms vs 111±39 ms, p = 0.02, respectively). According to ROC analysis, sum of spikes ≥ 3.5 most accurately predicted spontaneous VF with sensitivity of 100% and specificity of 87.5%.

Conclusions:
Right ventricular apical pacing enhanced or unmasked QRS fragmentation in the right precordial leads in patients with Brugada syndrome. Therefore, paced-QRS fragmentation could be a novel predictor for spontaneous VF in patients with Brugada Syndrome.
Abstract 12198: Effect of Repeat Intravenous Infusion of Vepoloxamer (Purified Sodium-Free Poloxamer 188) on Left Ventricular Systolic Function in Dogs With Advanced Heart Failure
Authors: Sabbah Hani N , Wang Mengjun , Zhang Kefei , Gupta Ramesh C , Emanuele Marty
Published: April 2024

Introduction:
Ca
2+
overload occurs in heart failure (HF) leading to cardiomyocyte dysfunction and death. Vepoloxamer (VEPO), purified sodium-free poloxamer 188, is a rheologic agent that, in HF, has been suggested to improve microvascular blood flow and repair damaged cell membranes, possibly inhibiting unregulated Ca
2+
entry into cardiomyocytes. We examined the effects of repeat acute i.v. infusion of VEPO on LV function in dogs with microembolization-induced HF (LV ejection fraction, EF~30%).

Methods:
14 HF dogs were randomized to 2 hours infusions of VEPO (450 mg/kg, n=7) or v/v normal saline (control, n=7). Each dog received 2 infusions of VEPO or saline 3 weeks apart. Dogs were followed for an additional 3 weeks after the 2
nd
infusion (total follow-up 6 weeks). LV end-diastolic (EDV) and end-systolic (ESV) volumes, EF, and plasma n-terminal-pro brain natriuretic peptide (nt-pro BNP) were measured at baseline, at end infusion 1
st
infusion, and at 24 hours, 1, 2 and 3 weeks thereafter and then again at 24 hours, 1, 2 and 3 weeks after the 2
nd
infusion. The change between baseline and other time points (treatment effect, Δ) was calculated.

Results:
Data are shown in the table. Saline had no effect on any measures. Compared to saline control, VEPO reduced ESV and nt-pro BNP and increased EF without affecting EDV, heart rate or aortic pressure. The benefits were sustained for up to at least 2 weeks after the 1
st
VEPO dose and up to 3 weeks after the 2
nd
dose.

Conclusions:
Therapy with multiple intravenous 2 hours infusions of VEPO, pulsed at 3 week intervals, elicit progressively sustained improvement in LV systolic function evident for at least 6 weeks. The results support development of MST-188 for the treatment of acute HF and potentially for continued therapy post-hospital discharge.
Abstract 12290: Exosomal miR-223 Contributes to Mesenchymal Stem Cell-Elicited Cardio-protection in Polymicrobial Sepsis
Authors: Wang Xiaohong , Huang Wei , Wang Yigang , Fan Guo-Chang
Published: April 2024

Background:
Mesenchymal stem cells (MSCs) have been shown to elicit cardioprotective effects in polymicrobial sepsis induced by cecal ligation and puncture (CLP). However, the underlying mechanisms remain obscure. While recent studies have indicated that miR-223 is highly enriched in MSC-derived exosomes, whether exosomal miR-223 contributes to MSC-mediated cardioprotection in sepsis is unknown.

Methods and Results:
MSCs harvested from the bone marrow of female pre-miR-223 knockout (KO) and wild-type (WT) mice were injected into male WT mice via the tail vein 1 h after CLP. We observed that the mortality of mice at 32h post-CLP was significantly reduced in WT- MSC-injected mice, but not in KO-MSC-treated groups, compared with controls. CLP-triggered cardiac dysfunction, apoptosis and inflammatory response were also attenuated in mice treated with WT-MSCs, but not miR-223 KO-MSCs. Furthermore, in vitro study showed that WT-MSCs could release miR-223-enrinched exosomes (WT-exosomes) that were taken up by macrophages and cardiomyocytes, leading to reduced production of pro-inflammatory factors (TNF-α, IL-1β, and IL-6) from macrophages and cardiomyocyte death upon LPS insults. By contrast, miR-223-KO-exosomes stimulated macrophage to release these cytokines and increased cardiomyocyte death upon LPS challenge. In vivo study showed that injection of KO-exosomes into the tail vein of mice at 1h post-CLP significantly increased: 1) serum levels of TNF-α, IL-1β, and IL-6; 2) cardiac dysfunction; and 3) animal mortality. Conversely, treatment of mice with WT-exosomes displayed the opposite effects. Mechanistically, we identified that miR-223-KO exosomes contained higher levels of Sema3A and Stat3, two known targets of miR-223 (5p & 3p), than WT-exosomes. Accordingly, these exosomal proteins were able to be transferred to macrophages and cardiomyocytes, leading to increased inflammation and cell death. By contrast, WT-exosomes encased higher levels of miR-223, which could be delivered to macrophages and cardiomyocytes, resulting in down-regulation of Sema3A and Stat3.

Conclusions:
These data for the first time indicate that exosomal miR-223 plays an essential role for MSC-induced cardioprotection in sepsis.
Abstract 12330: Comparison Between Optical Frequency Domain Imaging Guided and Intravascular Ultrasound Guided Balloon Pulmonary Angioplasty for the Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Ikeda Nobutaka , Kubota Shuji , Okazaki Toru , Hara Hisao , Hiroi Yukio
Published: April 2024

Introduction:
The balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is an emerging procedure. High-resolution imaging is useful to visualize the complex structures in the pulmonary arteries of CTEPH. The use of intravascular ultrasound (IVUS) during BPA has reduced complications. Optical frequency domain imaging (OFDI) has been suggested to be a promising alternative to IVUS for the visualization of coronary arteries.

Hypothesis:
We assessed the hypothesis that OFDI guided BPA is comparable or superior to IVUS guided BPA.

Methods:
All complications related with BPA procedures and used balloon sizes for consecutive 141 lesions were recorded. In 23 lesions, both OFDI and IVUS were performed and obtained 48 pairs of images to assess the association of the measurements.

Results:
Among the 141 lesions, 47 lesions were treated by OFDI guided and 94 lesions were treated by IVUS guided. OFDI provided clear high-resolution images of pulmonary arteries of CTEPH (Figure). There was no significant difference in occurrence of complications between OFDI and IVUS guided (11% vs. 16%, ns). In 23 lesions (both OFDI and IVUS were performed), vessel area (VA) and lumen area (LA) measured by OFDI were smaller than those of IVUS. However, significant high correlations were found between the two measurements(VA: r=0.78 p<0.0001 and LA: r=0.75 p<0.0001). Less inter- and intra-observer variabilities were found in OFDI measurements than IVUS measurements. In all 141 lesions, used balloon diameters were not different between the OFDI and IVUS guided (2.9±0.8 vs. 2.8±0.9, ns).

Conclusions:
The safety of OFDI guided BPA was acceptable. High correlations between OFDI and IVUS measurements were observed. The reproducibility of OFDI measurements were excellent and higher than IVUS measurements. Balloon diameters which were decided OFDI and IVUS were not different. In conclusion, OFDI has a potential to refine BPA procedures.