bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15913: Statin And Ezetimibe in Silent Ambulatory Myocardial Ischemia (SESAMI Trial)
Authors: Kadro Waleed , Turkmani Maya , Rahim Hussam , Beshir Oussama , Khatib Oussama , Jaha Najeeb , Younis Ashraf , Pakkal Kishan
Published: July 2021

Introduction:
Cholesterol lowering is associated with a reduction in cardiovascular morbidity and mortality. Statins are the main drugs for cholesterol lowering. Ezetimibe when added to statins gives further reduction in cholesterol but its long-term effect on cardiovascular morbidity and mortality and ischemic events is not known. This study sought to determine whether further cholesterol lowering with ezitimibe will also results in a reduction of myocardial ischemia during daily life.

Hypothesis:
Further cholestrol with ezetimibe lowering may reduce silent ischemia.

Methods:
We enrolled 50 patients with proven stable coronary artery disease (CAD) and at least one episode of ST-segment depression on ambulatory ECG monitoring. All of them were receiving optimal therapy for CAD including statin therapy for cholesterol reduction. 25 patients were randomized to continue their statin therapy (Statin only group) and 25 to recieve statin plus Ezitimibe 10mg/day (ezitimibe group). Serum cholesterol and LDL cholesterol levels and ambulatory monitoring were repeated after 4 to 6 months of therapy. The two groups were comparable with respect to baseline characteristics, number of episodes of ST-segment depression, and baseline serum cholesterol levels. Holters were read by a blinded cardiologist.

Results:
The ezitimibe group had lower mean total and LDL cholesterol levels at study end and experienced a significant reduction in the number of episodes of ST-segment depression compared with the statin only group. ST-segment depression was completely resolved in 13 of 25 patients (52%) in the ezitimibe group versus 3 of 25 (12%) in the statin only group. The ezitimibe group exhibited a highly significant reduction in ambulatory ischemia (P<.001). By logistic regression, treatment with ezitimibe was an independent predictor of ischemia resolution.

Conclusions:
Further cholesterol lowering with ezitimibe can result in reduction or resolution of myocardial ischemia recorded as episodes of ST-segment depression in ambulatory monitoring of the ECG. A larger study is required to confirm this results. This may be translated into long term mortality reduction for CAD by adding ezetimibe.
Abstract 15949: High Intensity Interval Training is Superior to Continuous Training and Reverses RV Remodeling and Dysfunction in a Rat Model of Pulmonary Hypertension
Authors: Brown Mary Beth , Neves Evandro , Novack Rachel , Fisher Amanda , Presson Robert , Petrache Irina , Kline Jeffrey , Lahm Tim
Published: July 2021

Exercise appears to have overall benefit in pulmonary arterial hypertension (PAH); however, studies to date indicate little effect on the elevated pulmonary pressure or RV hypertrophy (RVH) and dysfunction associated with the disease. High intensity interval training (HIIT) is reported to be superior to the more customary prolonged continuous exercise training (CExT) protocol for chronic heart failure but has not been tested for PAH. Therefore, we investigated impact of a 6 wk HIIT vs. CExT treadmill program in a monocrotaline rat model of mild PAH (MCT, 40 mg/kg) on indicators of disease progression.

Methods:
Treadmill training was performed 5x/wk in male Sprague-Dawley MCT rats (250-300g), following a protocol of either HIIT (5 cycles of 2 min at ~90% VO
2
reserve [VO
2
R] + 3 min at 30% VO
2
R; n=8), or low intensity CExT (60 min at 50% VO
2
R; n=7). Statistical analysis was performed by one-way ANOVA.

Results:
MCT-induced decrements in VO
2
max were ameliorated by both HIIT and CExT (p
<
0.01 vs. sedentary MCT rats, MCT-SED, n=6), and were similar to healthy controls (CON, n=6). Most importantly, RV systolic pressure (RVSP, in mmHg; via Millar catheter) and RVH (ratio of RV to LV+S mass) were lowered (p<0.05) only by HIIT (28.7±2, and 0.32±0.02) and not by CExT (44.1±3, and 0.43±0.01) vs. MCT-SED (40.2±3.2, and 0.41±0.02). Cardiac output (Δ from baseline in μl, via RV echocardiography) was also improved by HIIT (117±28) vs. MCT-SED (6±42, p=0.04). Additional hemodynamic recordings
during
running, via novel implantable telemetry (DSI), were obtained serially at pre- and 2, 4, 6, and 8 wks post-MCT, and revealed ‘surges’ in RVSP during HIIT, vs. a steady RVSP pattern during CExT. Pulmonary eNOS (per immunoblotting) was increased (p<0.05) with HIIT, consistent with greater endothelial stimulation. Conclusions: HIIT is superior to CExT for improving hemodynamics and RV remodeling and dysfunction in MCT rats and warrants further investigation in other models and in patients. More favorable outcomes may be explained by greater sheer-stress mediated vascular endothelial adaptation to HIIT stimulus, or lower cumulative training-induced RV wall stress with the briefer HIIT session duration.
Abstract 15959: N-6 Polyunsaturated Fatty Acids in RBC Membranes and Estimated Desaturase Activities and Risk of Sudden Cardiac Death
Authors: Chiuve Stephanie E , Cook Nancy R , Moorthy M V , Gaziano J M , Campos Hannia , Albert Christine M
Published: July 2021

Introduction:
Fatty acids in cell membranes modify the propensity for ventricular arrhythmias. In experimental studies, linoleic acid (LA;18:2n-6) has anti-arrhythmic effects, but its association with sudden cardiac death (SCD) risk has been inconsistent. Further, little is known about circulating levels of other n-6 polyunsaturated fatty acids(PUFA) and SCD risk.

Methods:
In a case-control analysis nested within 6 prospective cohort studies, we measured RBC levels of LA, γ-linolenic acid (GLA;18:3n-6), dihomo- γ-linoleic acid (DGLA;20:3n-6) and arachiodonic acid (AA; 20:4n-6) in 442 cases of SCD and 852 controls matched on age, sex, race, antecedent CVD, smoking status and fasting status using risk-set sampling. We estimated the activity of 2 key enzymes in n-6 PUFA metabolism, Δ-6desaurase (D6D), which converts LA to GLA, and Δ-5desaturase (D5D), which converts DGLA to AA, using their product to precursor ratios. The multivariable relative risks (RR) were estimated by conditional logistic regression adjusted for other CVD risk factors and n-3 PUFAs in each cohort separately and then combined with random effects meta-analyses.

Results:
DGLA was positivity linearly associated with risk of SCD while higher levels of AA were associated with lower risk of SCD. Additionally, higher D5D activity (DGLA/AA), representing greater metabolism of DGLA to AA, was inversely associated with risk (Table). Although LA demonstrated a U-shaped relation, with a nadir in SCD risk in quintile 3, the quadratic relation was not significant (p, quadratic trend = 0.95). Neither GLA nor D6D activity (GLA/LA) were associated with risk of SCD (Table).

Conclusions:
Higher RBC DGLA and lower RBC AA were associated with greater risk of SCD and greater estimated activity of the D5D was associated with lower risk. These n-6 PUFAs are not determined by n-6 PUFA intake and thus research on the regulation of DGLA and AA in cell membranes is warranted and may identify novel targets for SCD prevention.
Abstract 15981: DNA Single-strand Break-induced DNA Damage Response Causes Heart Failure
Authors: Higo Tomoaki , Naito Atsuhiko , Shibamoto Masato , Lee Jong-Kook , Hikoso Shungo , Sakata Yasushi , Komuro Issei
Published: July 2021

Introduction:
The DNA damage response (DDR) pathway is activated upon DNA damage. In mitotic cells, the DDR plays essential role in maintaining genomic stability and preventing cancer formation. DNA damage and activation of the DDR are also observed in the post-mitotic cardiomyocytes of patients with end-stage heart failure, however, their roles in the pathogenesis of heart failure remains elusive.

Methods and Results:
We performed transverse aortic constriction (TAC) operation to produce mice model of pressure-overload induced heart failure. Alkaline- and neutral- comet assay revealed that unrepaired DNA single-strand break (SSB), not double-strand break, is accumulated in cardiomyocytes of the failing heart. Mice with cardiomyocyte-specific deletion of XRCC1, a scaffold protein essential for SSB repair, exhibited more severe heart failure and higher mortality after TAC operation. Knockdown of Xrcc1 using siRNA produced SSB accumulation in cardiomyocytes and SSB accumulation induced persistent DDR through activation of ataxia telangiectasia mutated (ATM) kinase. Activated ATM also induced nuclear translocation of NF-κB and increased the expression of inflammatory cytokines. Activation of DDR, nuclear translocation of NF-κB, and increased expression of inflammatory cytokines were also observed in the failing heart and were enhanced in the heart of cardiomyocyte-specific XRCC1 knockout mice.

Conclusions:
Unrepaired DNA SSB accumulates in post-mitotic cardiomyocytes and plays a pathogenic role in pressure overload-induced heart failure. Approaches that promote efficient SSB repair or suppress aberrant activation of DDR pathway may become a novel therapeutic strategy against heart failure.
Abstract 16005: Highly Efficient Derivation of Human Pacemaker Cells From Pluripotent Stem Cells in Chemically Defined Conditions
Authors: Ghazizadeh Zaniar , Fattahi Seyedeh Faranak , Sharifi-tabar Mehdi , Mirshahvaladi Shahab , Shabani Parisa , Fonoudi Hananeh , Baharvand Hossein , Lee Bong Hee , Aghdami Nasser , Evans Todd , Chen Shuibing , Salekdeh Ghasem H
Published: July 2021

The cardiac conduction system is a complex network of cells that together orchestrate the rhythmic and coordinated depolarization of the heart. Dysfunction of the cardiac conduction system plays a central role in the pathogenesis of arrhythmia. While much progress has been made understanding cardiomyocyte differentiation, the molecular mechanisms regulating the specification and patterning of cells that form this conductive network is largely unknown.

The LIM-homeodomain transcription factor ISL1 is highly expressed in the secondary heart field (SHF) progenitor population that makes a substantial contribution to the developing heart, comprising most cells in the right ventricle, both atria and pacemaker cells. Pacemaker cells comprise the most proximal component of the cardiac conduction system, which have been proposed as the source of most arrhythmogenic events. Their dominance on other spontaneous beating cell types makes them a suitable target for pharmacologic compounds, making access to this cell lineage necessary for the study of new therapeutic agents.

To identify the signaling pathways that control the differentiation of human embryonic stem cell (hESC)-derived SHF cells into pacemaker cells, we performed RNA sequencing to compare the hESC-derived ISL1
+
population, non-enriched population and undifferentiated hESCs. Furthermore, using a small molecule screen we identified compounds that can improve differentiation of hESCs toward pacemaker cells.

Pathway analysis identified the Wnt pathway as the most significant regulator of SHF specification. Further differentiation of human pluripotent stem cells by stage-specific activation of BMP and WNT signaling pathways resulted in phenotypic pacemaker cells, which display morphological characteristics. More than 80% of these cells stained positively for HCN4, Contactin2(CNTN2) and GATA6, key markers of pacemaker cells. The differentiated cells express pacemaker markers, including
CNTN2, TBX2, TBX3, HCN4, TBX18, GATA6
indicated by qRT-PCR. They show inward potassium currents through HCN channels in patch clamp experiments.

Our data provides a new strategy to obtain human cardiac conduction cells in large scale for disease modeling, drug screening and cell therapy.
Abstract 16014: Gender Differences in Characteristics, Treatment and Outcomes in a Regional System of Cardiac Arrest Care
Authors: Bosson Nichole , Fang Andrea , Kaji Amy H , Thomas Joseph L , Niemann James T
Published: July 2021

Introduction:
Gender differences have been noted in outcomes from out-of-hospital cardiac arrest (OHCA) but remain poorly defined. The purpose of this study was to evaluate gender differences in OHCA characteristics, interventions, and outcomes.

Methods:
This is a retrospective analysis of registry data from a regionalized cardiac arrest system. Patients treated for OHCA with return of spontaneous circulation (ROSC) are transported to the nearest cardiac arrest receiving center with percutaneous coronary intervention (PCI) capability and therapeutic hypothermia protocols. Outcomes are reported to a single registry, from which all adult patients were identified from 2011 through 2014. The characteristics, treatment interventions, and outcomes were evaluated by gender and then further stratified by ECG presence of STEMI and initial rhythm. The adjusted odds ratio (OR) for survival with good neurologic outcome (defined as cerebral perfusion category (CPC) 1 or 2) was calculated for women compared to men.

Results:
There were 5174 OHCA in the registry, 3080 males and 2094 females. Women were older, median 71 years (inter-quartile range (IQR) 59-82) vs 66 (IQR 55-78) and, despite similar frequency of witnessed arrest, were less likely to present with a shockable rhythm (22% vs 35%, Risk Difference (RD) 13% 95%CI 11-15%) compared to men. Women were also less likely to have STEMI on the ECG (23% vs 32%, RD 13% 95%CI 7-11%) receive catheterization (11% vs 25%, RD 14% 95%CI 12-16%), PCI (5% vs 14%, RD 9% 95%CI 7-11%) or TH (33% vs 40%, RD 7% 95%CI 4-10%). Women had decreased survival to hospital discharge (33% vs 40%, RD 7% 95%CI 4-10%) and a lower proportion with good neurologic outcome (16% vs 24%, RD 8% 95%CI 6-10%). The differences persisted with stratification by STEMI or initial rhythm. However, after adjustment for age, arrest characteristics (initial rhythm, witness, bystander CPR), interventions (catheterization, PCI, and TH) and interaction between gender and treatment, female gender was not associated with decreased survival with good neurologic outcome, OR 0.9, 95%CI 0.7-1.1.

Conclusion:
Gender-related differences in OHCA characteristics and treatment (including PCI, catheterization, and TH) are independent predictors of outcome disparities.
Abstract 16028: Contrast Enhancement Dynamics of Radiofrequency Ablation Lesions
Authors: Linstroth Lee , Angel Nathan A , Kholmovski Eugene , Macleod Rob , Silvernagel Josh , Marrouche Nassir , Ranjan Ravi
Published: July 2021

Introduction:
Late gadolinium enhanced MRI (LGE-MRI) done acutely after ablation shows a central area of no-reflow that enhances slowly. The dynamics and predictive value of this region to chronic lesion volume is unknown.

Methods:
RF lesions were created in a canine ventricle model using a 4 mm irrigated tip catheter. 3D LGE-MRI images were acquired in a 3T (Verio, Siemens) MR scanner (1.25 x 1.25 x 2.5 mm
3
) at weeks 0, 1, 2, and 4 post ablation at multiple time points after contrast injection (Multihance, 0.15 mmol/Kg). The central no-flow volumes in MRI were normalized to the histological volumes and this ratio was compared across multiple post-contrast injection times.

Results:
The number of lesions analyzed was 33, 27, 11 and 20 at week 0, 1, 2 and 4, respectively in four animals. Histological volumes had a mean of 99±52 mm
3
(range 32-220 mm
3
). The initial MRI done within five mins of contrast injection had average no reflow volumes of 330±170 mm
3
for week 0, 270±170 mm
3
at week 1, 120±100 mm
3
at week 2, and 50±46 mm
3
at week 4. The normalized no reflow volumes (normalized to chronic histological volume) for the initial MRI was 4.28±1.44 at week 0, 3.40±1.15 at week 1, 1.94±0.68 at week 2, and 0.65±0.42 at week 4. Based on a logarithmic fit to the decay in volume, the no reflow volume equaled the final histological volume 26.6 mins after contrast injection on day 0, 30.9 mins on week 1, 8.2 mins on week 2 and 0.3 mins after week 4. By one month after ablation, the no-reflow was negligible and the final lesion completely enhanced immediately after contrast injection.

Conclusions:
The no-reflow volume declines exponentially acutely after ablation and results in an accurate assessment of final lesion volume 26 to 30 minutes after contrast injection up to one week post - ablation. With tissue remodeling, the no reflow area enhances faster such that one month after ablation, lesions enhance completely immediately following contrast injection.
Abstract 16038: Heterozygous Endothelin Receptor Type B Knockout Confers Cardiac Resistance to Extreme Hypoxia in Mice
Authors: Stobdan Tsering , Zhou Dan , Ao-Ieong Eilleen , Ortiz Daniel , Ronen Roy , Bafna Vineet , Cabrales Pedro , Haddad Gabriel G
Published: July 2021

Rationale:
To better understand human adaptation to hypoxia, we took advantage of one of the nature’s experiments at high altitude (HA) and studied Ethiopians, a human population that is well adapted to HA hypoxia. Using whole genome sequencing, we identified EDNRB, endothelin receptor type B, as a candidate gene involved in HA adaptation.

Objective:
We hypothesize that EDNRB plays a critical role in hypoxia and therefore in HA adaptation through regulating cardiac function.

Methods and Results:
We generated EdnrB knockout mice and found that the EdnrB-/+ mice were phenotypically normal. However, when treated with lower levels of oxygen (O2), EdnrB-/+ mice tolerated various levels of hypoxia, sustaining ejection fraction, cardiac contractility and cardiac output to even 5% O2. Blood lactate levels remained low and O2 delivery to vital organs was significantly higher in EdnrB-/+. Tissues sensitive to hypoxia, such as brain, heart and kidney, were less hypoxic indicating better peripheral perfusion.

Conclusion:
These data indicate that a lower level of EDNRB significantly improves cardiac performance and tissue perfusion under various levels of hypoxia. Our findings in EdnrB-/+ mice provide strong evidence that 1) EDNRB plays a key role in the adaptation to HA whereby a lower activation of EDNRB leads to a better cardiac performance under hypoxic conditions and 2) HA adaptation studies can be pertinent to understanding responses to acute hypoxia at sea level.
Abstract 16044: Measurements of Tissue Oxygen and Hemoglobin on A Near Infra-red Spectroscopy in Emergency Patients With Poor General Conditions
Authors: Saitoh Takeji , Satoh Hiroshi , Kanayama Naohiro , Niwayama Masatsugu , Hozumi Hironao , Takahashi Yoshiaki , Uchida Toshiyuki , Saotome Masao , Urushida Tsuyoshi , Katoh Hideki , Hayashi Hideharu , Yoshino Atsuto
Published: July 2021

Introduction:
In patients with poor general conditions, the conventional pulse oximetry is sometimes unable to determine the oxygen saturation because of peripheral arteriole constriction. The near infra-red spectroscopy (NIRS) can measure absolute concentration of oxygenated, deoxygenated, and total tissue hemoglobin. Purpose: This study aimed to investigate the potential of a novel minimized NIRS system in terms of measurements of tissue oxygen and hemoglobin.

Methods:
We enrolled 22 normal controls and 83 emergency patients who came to the emergency department with poor general conditions. The tissue oxygen saturation (StO2) and tissue hemoglobin index (T-HbI) on second finger pulp (SFP), thenar eminence (TE), and sternocleid muscle (SM) were measured in both groups.

Results:
(1) In all subjects including patients with cardio-pulmonary arrest, both the StO2 and T-Hbl values were obtained stably. (2) In the emergency patients, the StO2 value on SFP was lower than those on TE and SM (53% [49-56] vs. 57% [55-60] and 58% [53-62], median [inter-quartile range], p<0.01), whereas those in the normal controls were not different. The StO2 value on SFP was lower in the emergency patients than that in normal controls (60% [58-61], p<0.01). (3) In the emergency patients, the T-Hbl value on SBP was also lower than those on TE and SM (0.13 mM [0.11-0.15] vs. 0.25 [0.22-0.29] and 0.23 [0.18-0.29], p<0.01). The T-HbI value on SFP was also lower in the emergency patients than that in normal controls (0.18 mM [0.17-0.21], p<0.01).

Conclusion:
NIRS detected peripheral circulatory failure easily and immediately in the emergency patients.
Abstract 16098: Mechanism of Branch Pulmonary Artery Stenosis After the Arterial Switch Operation
Authors: Morgan Conall T , Mertens Luc , Grotenhuis Heynric , Yoo Shi-Joon , Seed Mike , Grosse-Wortmann Lars
Published: July 2021

Background:
Branch pulmonary artery (PA) stenosis, most commonly on the left, is a recognized postoperative complication of the arterial switch operation (ASO) for transposition of the great arteries. We hypothesized that greater rightward rotation of the neopulmonary root and dilation of the ascending aorta are associated with stenosis of the left PA (LPA).

Methods:
This study represents a retrospective analysis of cardiac magnetic resonance imaging (CMR) studies performed in patients after ASO. Neo-pulmonary root position in relation to the aorta was expressed as an angle, with a negative angle implying a rightward neo-pulmonary root. For the purpose of this study, perfusion imbalance was defined as <40% of pulmonary blood flow to the affected lung. The offset between the LPA and right PA (RPA) as a result of cranial displacement of the LPA by asymmetric aortic root dilation was measured in the coronal plane.

Results:
74 patients / studies were included for analysis. 73% had no branch PA stenosis, 24% had LPA stenosis and 3% had RPA stenosis. LPA area indexed to BSA was smaller than RPA area (287 ± 185mm2 vs 151 ± 114mm2, p=0.001). Smaller LPA area correlated with reduced LPA flow (r=0.213, p=0.0001) and a greater rightward positioning of the neopulmonary to aortic root (r=0.361, p=0.002). There was no correlation between LPA size or flow and offset of the LPA take-off due to an enlarged aortic root. Patients with reduced relative LPA flow were more likely to have required pulmonary arterioplasty with the primary repair (17% vs 2%, p=0.04), had a smaller LPA area [102±102mm2 vs 160±108mm2, p=0.04) and a smaller anterior-posterior thoracic diameter (101±53mm vs 131±55mm, p=0.04). There was no significant difference in patient demographics, cardiac diagnosis, age at operation, aortic root dimension, ventricular volumetrics or ventricular function between patients with normal LPA flow vs. reduced LPA flow. Patients with reduced LPA flow did not have greater peak gradients on echo.

Conclusions:
Greater rightward rotation of the neopulmonary root is associated with reduced LPA size and likely contributes to the development of LPA stenosis after ASO.
Abstract 16108: Adverse Left Ventricular Remodelling Patterns Predict Response to Cardiac Resynchronization Therapy
Authors: Gonzalez Gerardo , Warriner David , Jackson Tom , Sammut Eva , Zacur Ernesto , Hose David Rodney , Razavi Reza , Smith Nicolas P , Lamata Pablo
Published: July 2021

Introduction:
The anatomy of the left ventricle (LV) remodels in heart failure. In this work we test the hypothesis that pre-implant LV shape can predict response to cardiac resynchronization therapy (CRT).

Methods:
The anatomy of the LV of 50 subjects selected for CRT was acquired and manually segmented from magnetic resonance imaging acquired using a steady-state free-precision 3D sequence. A computational atlas was built from 3D meshes that were fitted to the resulting segmentations, and was used to obtain atlas-based shape metrics from the cohort. Segmentation and 3D meshing was repeated in 19 cases to test the reproducibility of the new metrics.

Results:
The five most significant shape metrics were found to be reproducible. Response to CRT, defined as a reduction of a 10% in the end diastolic volume, was predicted by a linear combination of 2 atlas modes (AUC of 0.693, best operating point with sensitivity of 84% and specificity of 56%, as evaluated by a leave-1-out cross-validation test). The figure illustrates the overlay of the extreme geometry of responder (velvet) and non-responder (orange) shapes computed from the statistical shape model (the small red sphere is located at the septal wall): the adverse LV remodelling shows a shorter septal wall and angled basal plane.

Conclusions:
Pre-implant LV shape, described through novel atlas-based metrics, is a potential new criterion for CRT patient selection.
Abstract 16144: Association Between Elevated Initial Trauma Center Body Temperature and Non-mortality Outcomes Following Major Traumatic Brain Injury
Authors: Gaither Joshua B , Chikani Vatsal , Spaite Daniel W , Smith Jennifer J , Curry Merlin , Mhayamaguru Moses , Barnhart Bruce , Adelson P. David , Viscusi Chad , Denninghoff Kurt , Bobrow Bentley J
Published: July 2021

Introduction:
During prolonged hospitalization for Traumatic Brain Injury (TBI), fever has been identified as a possible cause of secondary brain injury and previous reports have identified an association between elevated body temperature and increased mortality following TBI. However, little is known about the relationship between an elevated initial trauma center body temperature (ITCT), measured immediately after EMS transport, and non-mortality outcomes. The purpose of this study was to determine if a correlation exists between elevated ITCT and various important patient outcomes.

Methods:
All moderate/severe TBI cases (CDC Barell Matrix Type 1) in the Arizona State Trauma Registry (ASTR; 1/1/07-12/31/12) were analyzed by the following ITCT categories: 36.5-37.9°C (normal-NT), 38.0-38.9°C (elevated-ET) and ≥39.0°C (very elevated-VET). Outcomes included: Trauma Center (TC) length-of-stay (LOS), Intensive Care Unit (ICU) LOS, and total TC charges. For continuous variables, non-parametric Kruskal-Wallis test was used to assess the median difference between the ET and VET cohorts and the NT group (reference). Wilcoxon two-sample tests identified groups with significant differences (alpha = 0.05).

Results:
22,925 cases met inclusion criteria (exclusions: missing ITCT-2,885; missing demographics-700; ITCT <36.5°C - 8953). Both ET and VET had significantly longer TC LOS/ICU LOS and higher total hospital charges compared to the NBT group (all p values <0.0001; Figure 1).

Conclusion:
In this statewide study, ET or VET were associated with longer ICU LOS, longer hospital LOS and increased hospital charges. Future work is needed to identify the causes of temperature elevations that occur during prehospital TBI care (e.g., environmental factors versus autonomic dysregulation) and whether initiation of in-field measures to prevent temperature elevation might improve outcome.
Abstract 16163: Hydrogen Sulfide Reduces Inflammasome Formation in Mice With Ischemic HFrEF
Authors: Mauro Adolfo G , Valle Raleigh Juan , Nguyen Khoa , Durrant David E , Kim Erica , Pottanat Paul , He Jun , Toldo Stefano , Abbate Antonio , Salloum Fadi N
Published: July 2021

Background:
Hydrogen sulfide (H2S) has been shown to attenuate myocardial ischemia/reperfusion injury via suppression of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Whether the H2S donor, Na2S, protects against ischemic heart failure with reduced ejection fraction (HFrEF) when treatment is initiated after development of LV dysfunction is unknown.

Methods and Results:
Adult male mice underwent myocardial infarction (MI) by permanent coronary artery ligation after baseline echocardiography. Repeat echocardiography was performed at day 3 post MI and surviving mice with fractional shortening (FS) less than 25% were treated with either Na2S (100 μg/kg, ip) or saline (volume matched, ip) for 25 days. LV fractional shortening remained unchanged at 7 and 28 days post-MI in the saline group, but improved significantly with Na2S at both time points (Fig. A). Moreover, LV infarct scar size, assessed by trichrome staining, was smaller in Na2S group (14.8 ± 2.1%) as compared to control (28.8 ± 4.8%, P<0.05) at 7 days post MI. Immunofluorescence staining for apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), a component of the inflammasome, showed significant increase at 3 days post MI with sustained elevation at 7 days in the saline-treated group, whereas treatment with Na2S starting on day 3 post-MI significantly attenuated ASC 4 days later (Fig. B). Survival rate was 2-fold higher in Na2S group compared to saline control at 28 days post MI (P<0.05, Fig. C).

Conclusion:
Treatment with Na2S in mice with ischemic HFrEF improves LV function and survival up to 28 days post MI, possibly through suppression of ASC and prevention of further NLRP3 inflammasome formation. We propose that H2S donors can be promising therapeutic tools for ischemic HF.
Abstract 16184: Elevated Maternal Glucose Levels During Gestation may Confer Specific Risk for Tetralogy of Fallot
Authors: Priest James R , Yang Wei , Reaven Gerald , Knowles Joshua W , Shaw Gary M
Published: July 2021

Introduction:
Clinicians have long observed an association between maternal diabetes and risk of congenital heart disease (CHD) in offspring. Though the clinical diagnoses of Type 2 diabetes or gestational diabetes are strong maternal risk factors, this diagnostic classification captures only a subset of patients with overt hyperglycemia not more subtle abnormalities of glucose or insulin metabolism. We explored the potential risk for two different CHD phenotypes in offspring with with midpregnancy measures of glucose, insulin, and insulin resistance.

Hypothesis:
We hypothesize that continuous measures of blood analytes related to maternal diabetes will be associated with the risk for two CHD phenotypes tetralogy of Fallot (ToF) and d-Transposition of the Great Arteries (dTGA) which have been recently associated with overt diabetes.

Methods:
We assembled a prospective cohort of 277 women carrying infants with ToF (n=55), dTGA (n=42), or nonmalformed control infants without CHD (n=180), and measured serum insulin by a validated radioimmunoassay and glucose levels in second trimester blood samples. We performed univariable as well as multivariable analyses to investigate statistical associations.

Results:
Maternal glucose levels were associated with elevated risk for both CHD phenotypes in offspring with an adjusted odds ratio (OR) of 6.61 (95%CI 1.67-26.13), which in subgroup analysis was driven by a strong association with ToF (OR 18.45, 95%CI 3.34-102.08) compared to the much lower OR for dTGA (OR 1.24, 95%CI 0.16-9.59).

Conclusions:
We observed that maternal blood glucose levels are strongly associated with risk for ToF, which is consistent with recent epidemiological data. These results represent the first direct correlation of glucose as a continuous variable to risk for specific cardiac malformations. In conclusion the association between serum glucose and risk for ToF suggest the need for additional epidemiological and mechanistic investigations into the risk for conferred by insulin signaling and glucose metabolism during early pregnancy.
Abstract 16186: Hypoxic Pre-conditioning on Human CD34+ Stem Cells Enhances Exosome Therapeutics of Ischemic Tissue Repair Through ETS-1-Regulated Pathway
Authors: Liang Yaxuan , Mathiyalagan Prabhu , Kim David , Losordo Douglas , Hajjar Roger , Sahoo Susmita
Published: July 2021

Previous studies in our lab have revealed a novel mechanism that therapeutically important human CD34+ stem cells secrete exosomes (Exo) to extracellular milieu that induce angiogenic activity independent of the cells. Further studies demonstrated that CD34+ exosomes (CD34Exo) carry and transfer of proangiogenic miRNAs, such as miR-126, which affect the therapeutic function of the exosomes.

Herein we hypothesized that hypoxic treatment of CD34+ stem cells can modulate the miRNA content and regenerative efficacy of CD34Exo.

Methods and Results:
Exosomes from human CD34+ cells cultured under hypoxia (H-Exo) were more proliferative, anti-apoptotic and angiogenic in vitro, as compared to exosomes from cells under normoxia (N-Exo). In a mouse model of hind limb ischemia, H-Exo treatment significantly enhanced perfusion (ratio: 0.93±0.05 v 0.77±0.02), increased capillary density (1.6±0.2 v 1.1±0.1/HPF) and prevented ischemic limb amputation (0% v 37.5%) as compared to N-Exo (p<0.05; n=7-8). Flow cytometry and confocal microscopy indicated that H-Exo was uptaken by endothelial cells in the ischemic limb. Interestingly, hypoxic treatment did not alter the size and quantity of Exo or expression of major proteins of CD34Exo compared with normoxic treatment. However, hypoxic treatment altered the proangiogenic miRNA expression in H-Exo including miR-210 and miR-126. ETS-1, a transcription factor induced by hypoxia-inducible fator-1 (HIF-1) is known to regulate expression of miR-126. We have examined the protein and RNA expression of HIF-1 and ETS-1 in Sca-1 positive mouse hematopoietic stem cells, and propose that HIF-1/ETS-1 regulatory mechanisms affect the expression of exosomal miR-126 under hypoxia. These results are being confirmed in human CD34+ cells using siRNA silencing and HIF hydroxylase inhibitor dimethyloxalylglycine.

Conclusion:
Hypoxia induced miR-126 expression in CD34 cell-derived exosomes stimulating exosomes-mediated angiogenesis and therapeutic recovery via ETS-transcriptional pathway. Our work has important clinical implications for therapeutic angiogenesis, especially in diabetic and cardiovascular patients who have stem cells with diminished angiogenic potential.
Abstract 16193: Sport Activity and Sudden Cardiac Death in Women
Authors: Basso Cristina , Rizzo Stefania , Pilichou Kalliopi , Carturan Elisa , Thiene Gaetano
Published: July 2021

Background:
No specific data are available on the prevalence and characteristics of cardiac sudden death (SCD) during sport activities among young women.

Methods and Results:
From a prospective 30-year target project on SCD in the young, involving 695 subjects 1-40 years old who died suddenly in the same geographic areas, 649 were due to SCD (196 female, 30%). A total of 76 young adults were competitive athletes and died during or soon after effort (11%). Only 6 (8%) of such events occurred in women (mean age 23±10 yrs, range 12-38), specifically during jogging (2), and swimming, volley, gymnastic and triathlon (one each). Cause of death seemed more likely to be associated with structurally normal heart in women compared with men (50% versus 7%; P<0.01). In particular, while inherited cardiomyopathies (i.e. arrhythmogenic, hypertrophic and dilated) and coronary atherosclerosis are the leading cause in the overall population of athletes (24/76, 32% and 11/76, 14.5% respectively) and in the male sub-group (24/70, 34% and 11/70, 16%, respectively), they were never observed in female athletes.

Conclusions:
Sports-related SCD in women is dramatically less common compared with men. In the female athletic population, SCD occurs in the setting of a structurally normal heart in half of cases. In a country with obligatory pre-participation screening for sport activity, inherited cardiomyopathies and atherosclerotic coronary artery diseases are almost exclusive of the male athletic population.
Abstract 16212: Warranty Period of Zero Coronary Artery Calcium Score in Asymptomatic Korean Individuals
Authors: Lee Ji-hyun , Han Dong-hee , ó Hartaigh Bríain , Gransar Heidi , Choi Su-Yeon , Sung Ji-dong , Min James K , Chang Hyuk-Jae
Published: July 2021

Introduction:
Zero coronary artery calcium (CAC) is a reliable predictor of absent atherosclerosis and serves as a useful adjunct for identifying those at low risk. Despite this, the “warranty period” that displays the protective value associated with the absence of CAC towards experiencing a cardiovascular event among Asians is not well established.

Hypothesis:
To examine whether the absence of CAC displays a more favorable warranty period for all-cause death compared with the presence of CAC in a Korean cohort.

Methods:
A total of 48,215 asymptomatic Koreans (mean age: 54±8.8 years; 25% women) were enrolled and stratified by the absence or presence of CAC. Time to exceeding 1% of cumulative all-cause death was estimated in order to identify low-risk individuals. Hazard ratios (HR) with 95% confidence intervals (95% CI) for all-cause death were estimated according to prespecified cardiac risk factors and the presence of CAC.

Results:
In total, 30,605 (63.5%) individuals presented with a zero CAC. Across a median follow-up of 4.4 years (Interquartile range: 2.7-6.6 years), 415 (0.9%) individuals experienced the endpoint of all-cause death. For those with a zero CAC, the time to exceeding 1% risk was found to be 9 years, indicating a substantially longer warranty period compared with participants with a CAC>0 (e.g., 5 year warranty period). The time to exceeding 1% risk tended to decline for individuals on the background of increasing CAC scores. For each of the other prespecified risk factor groups, a zero CAC provided a longer cumulative event free period than in the presence of any CAC. Cox regression analyses also revealed that the absence of CAC was independently associated with a lower risk of all-cause death in each of the respective risk factor groups when compared with CAC>0.

Conclusions:
In a large cohort of asymptomatic Korean individuals, the absence of CAC evokes a strong protective effect against all-cause death as demonstrated by a longer warranty period.
Abstract 16236: The Majority of Laypersons Trained in CPR Do Not Maintain Current Certification or Training
Authors: Blewer Audrey L , Leary Marion , Ikeda Daniel , Becker Lance B , Abella Benjamin S
Published: July 2021

Background:
Recent work has demonstrated that U.S. CPR training rates are low, yet few studies have measured the overall prevalence of CPR education and whether individuals have maintained training over time. Furthermore, few studies have linked individual-level demographics with current maintenance of CPR training. Quantifying these variations could help inform future targeted education initiatives.

Objectives:
We hypothesized that current CPR training frequency is low in Southeastern Pennsylvania (SEPA). As a secondary analysis, we examined gender and racial variation among those who are currently trained.

Methods:
We administered validated survey questions to assess CPR training status through the Community Health Household Survey, a semi-annual survey of 50,000 households in SEPA. Participants were contacted via random-digit-dialing using stratified sampling methods. Analysis was performed using categorical methods.

Results:
From 12/2014-2/2015, 10,048 participants completed the regional health household survey. Subjects mean age was 44±23 and 55% were female. Overall, 61% identified taking a CPR training course at some point in time, while only 18% were trained within the past two years; 15% identified being CPR certified. Of those who were certified, 76% sought certification for their vocation. CPR training status varied by gender, with more females identified being trained in the past two years compared to males (61% vs 39%, p<0.01). This gender distribution was similar among those who reported certification for their vocation (62% vs 38%, p<0.01). Additionally, current CPR training status varied by race; among those trained within two years, 62% were White, 27% were Black, and 6% were Latino (p<0.01).

Conclusions:
The overall prevalence of those currently trained or certified in CPR was low in SEPA. These data suggest that many individuals seek CPR training at some point, but few maintain current training or certification. Additionally, there was gender and racial variation among those currently trained within the past 2 years. These data suggest the need for programs to offer CPR skill refreshers among targeted layperson subpopulations. Future work may consider implementing a similar CPR training prevalence survey nationally.
Abstract 16251: Neuroprotection by Near-infrared Light in a Rat Stroke Model
Authors: Afzal Aqeela , Eells Janis T , Salzman Michele , Riess Matthias
Published: July 2021

Introduction:
Intravenous tissue Plasminogen Activator (tPA) is the only FDA approved pharmacological therapy for stroke. However, tPA can only be administered within 4.5 hours post stroke, and intracerebral hemorrhage remains a serious complication, severely limiting the use of tPA. Photobiomodulation (PBM) stimulates healing and repair of injuries by lowering swelling and inflammation. Targeting mitochondria, PBM results in modulation of reactive oxygen species, increased ATP production, activation of transcriptional factors, increased nitric oxide release and prevention of apoptotic cell death. Studies using ~809 nm light-emitting diodes (LED) have reported mixed results in animals and human clinical trials.

Hypothesis:
The use of 670 nm LED PBM rescues locomotor function in a rat model of ischemic stroke.

Methods:
A heat blunted nylon monofilament suture was introduced into the left common carotid artery and fed through the internal carotid artery into the middle cerebral artery of anesthetized male Sprague Dawley rats. Occlusion was maintained for 60 min and reperfusion achieved by removal of the filament. A 670 nm LED was used directly on top of the skull. One 90 sec treatment with a hand-held WARP10 device (Quantum Devices, Barneveld, WI, USA) delivered a power density of 50 mW/cm2 and a dose of 4 J/cm2. The light was administered at reperfusion, 2 hrs post and 24 hrs post reperfusion. Behavior was recorded in a Phenotyper cage pre and 24 hrs post stroke and analyzed using specialized software. Rats were euthanized 24 hrs post stroke, and their brains removed for infarct volume assessment by triphenyltetrazolium chloride staining. Statistics: ANOVA with Newman-Keuls post hoc test. Data are mean ± SEM, significance accepted at p < 0.05.

Results:
Rats treated with 670 nm LED PBM had significantly reduced infarct volumes compared to stroke alone (64±16% vs 83±14%). In addition, LED-treated rats showed better recovery of locomotor function: distance moved (sham control 3133±291, stroke 704±254, stroke+LED 3693±1953 cm).

Conclusions:
Our data suggest a potential neuroprotective role of 670 nm LED PBM in a rat experimental model of stroke.
Abstract 16285: Routine Use of 3D Mapping and Irrigated Ablation Improves Outcomes of Pulmonary Vein Antral Isolation Among Patients With Persistent AF
Authors: Alipour Pouria , Khaykin Yaariv , Pirbaglou Meysam , Pantano Alfredo , Ritvo Paul , Brown Patrick E , Olesovsky Shelby , Chun Lauren , Verma Atul
Published: July 2021

Bckground:
Pulmonary Vein Antrum Isolation (PVAI) is a widely accepted treatment option in Atrial Fibrillation (AF). However, despite procedural advancements, post-PVAI AF recurrences remain a common challenge. We thought to investigate whether the addition of routine 3D electroanatomical mapping and routine use of irrigated ablation catheters (IC) vs 8 mm tip catheters made an impact on the outcomes of PVAI guided by intracardiac echocardiography (ICE) and a decapolar circular mapping catheter (CMC) alone.

Methods:
Patient and procedural data were collected for 884 AF consecutive patients undergoing PVI at a single Canadian center during 2004 - 2014 (469 patients in 2004-2009, Group 1vs. 415 patients in 2010-2014, Group 2). Group 1 patients received PVAI guided by ICE and CMC. All Group 2 patients had PVAI guided by ICE, CMC and 3D mapping with the use of irrigated tip ablation catheters. Mean ages for Groups 1 and 2 were = 58.6 ± 10.0 and 61.0 ± 10.7 years respectively (p= 0.001). Mean follow up time was 17.1 ± 18.8 months for Group 1 and 14.1± 9.7 months for Group 2 (p=0.003). ECG and ambulatory monitoring was performed at 1, 3, 6, and 12 months. Recurrences ≤ 3 months post-PVI were considered Early (ER), while recurrences after 3 months post-PVI were considered Late (LR). Using survival analysis, rates of LR stratified by AF type [Paroxysmal AF (PAF) vs. Non-PAF (NPAF)] were compared between the two cohorts

Results:
ER rate was lower in Group 2 vs. Group 1 (36.8% vs. 44.7%, P=0.05) in patients with PAF and for those with NPAF (54.8% vs. 66.9%, P=0.03). LR rates did not differ between the Groups among PAF patients (62.5% in Group 1 vs. 57.3% in Group 2, P=0.16), but improved significantly for the NPAF patients (55.6% in Group 1 vs. 37.9% in Group 2 , P=0.002).

Conclusion:
Late recurrence of AF post-PVI has dramatically improved since 2010 for patients with persistent AF following routine addition of 3D mapping to ICE and CMC, while substituting an irrigated for an 8mm ablation catheter.
Abstract 16325: Short-Term Changes in Carotid Artery Inflammation Measured by Positron Emission Tomography are Associated With Long Term Atherosclerosis Progression Measured by Magnetic Resonance Imaging
Authors: Ishai Amorina , Joseph Philip , Mani Venkatesh , Kallend David , Rudd James , Fayad Zahi , Tawakol Ahmed
Published: July 2021

Introduction:
It is unknown whether short-term changes arterial wall inflammation are associated with changes in the rate of structural progression of atherosclerosis.

Hypothesis:
We assessed arterial inflammation, using positron emission tomography (PET) imaging and 18F-fluorodeoxyglucose (FDG) to test the hypothesis that short term changes in arterial inflammation predict long term atherosclerosis progression, measured by magnetic resonance imaging( MRI).

Methods:
Forty-two participants enrolled in the dal-PLAQUE study , who underwent both PET and MRI imaging of the carotid arteries were evaluated. Short-term change in arterial inflammation was measured as change in the carotid FDG target to background ratio [TBR] by PET between baseline and 6 months. The long-term rate of atherosclerotic plaque progression was assessed using MRI, as percent change in carotid mean wall area [MWA] and mean wall thickness [MWT] between baseline and 24 months.

Results:
The mean age of the population was 62.5 years, and 12 (28.6 %) were male. In participants with (vs. without) any increase in arterial inflammation over 6 months, long-term rate of change in MWT was significantly higher (% change MWT: 17.49% vs. 1.74%, p=0.038) and long-term rate of change in MWA was significantly higher (% change MWA: 25.50% vs. 3.59%, p = 0.027). Results remained significant after adjusting for clinical and biochemical covariates. Individuals with no increase in arterial inflammation over 6 months had no significant structural progression of atherosclerosis over 24 months, measured as MWT (p=0.616) or MWA (p=0.373).

Conclusions:
Short-term changes in arterial inflammation predict long-term atherosclerosis progression. In those with no increase in arterial inflammation, no significant changes in atherosclerosis progression were observed.
Abstract 16339: Heparin Bridging in Atrial Fibrillation Patients After Temporary Interruption of Warfarin: Evidence From Meta-analysis
Authors: Ayoub Karam , Nairooz Ramez , Almomani Ahmed , Marji Meera , Pino Maria , Maskoun Waddah
Published: July 2021

Background:
Patients with atrial fibrillation often require temporary interruption of warfarin for procedures. However, the efficacy of periprocedural heparin bridging in clinical practice is still unclear.

Methods:
We searched the literature for trials that compared heparin bridging to no bridging in atrial fibrillation patients for whom warfarin was temporarily interrupted. The incidence of all-cause mortality, thromboembolism, and major and all bleeding was included, and meta-analysis was performed.

Results:
A total of 11,924 patients with atrial fibrillation were included in 4 observational studies and 1 randomized trial. Mean CHADS2 score for the no heparin bridging group is 2.26 vs heparin bridging 2.26. At 30 days and up to 3 months, no bridging group in comparison to bridging group did not show any significant difference in mortality (odds ratio (OR), 1.22; 95% confidence interval (CI), 0.04-37.43; P = 0.91) or thromboembolism (OR, 0.69; 95% CI, 0.12-4.05; P = 0.68), but no bridging group showed significantly less major bleeding (OR, 0.43; 95% CI, 0.21-0.86; P = 0.02) and less all bleeding (OR, 0.43; 95% CI, 0.24-0.79; P = 0.007).

Conclusion:
Among atrial fibrillation patients anticoagulated with warfarin with an intermediate CHADS2 score requiring temporary interruption of warfarin for a procedure, periprocedural bridging with heparin was associated more with major and all bleeding when compared to no bridging, with no significant difference in mortality and thromboembolism.