bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15687: Triglyceride Levels and Non-Alcoholic Fatty Liver Disease: A Multivariable Mendelian Randomization Study
Authors: Gagnon Eloi , Gobeil Emilie , Bourgault Jerome , Arsenault Benoit
Published: June 2023

Introduction:
Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of the adult population worldwide. Individuals with NAFLD are twice as likely to develop atherosclerotic cardiovascular diseases compared to individuals without NAFLD. Whether plasma triglyceride levels increase NAFLD risk independently of other lipoprotein subfractions, and hence represent a potential therapeutic target for NAFLD, is unknown. Our objective was to investigate the causal effect of genetically predicted plasma lipids levels on NAFLD using multivariable Mendelian randomization.

Methods:
We performed univariable and multivariable two-sample MR to investigate the respective causal contribution of triglycerides, apolipoprotein B (apoB), and HDL-C on NAFLD. As genetic instruments for HDL-C, triglycerides and apo B levels, we selected all robustly (p<5e-8) and independently (linkage disequilibrium R2 < 0.001) genetic variants from genome-wide association studies in the UK Biobank (n = 441,016). As outcome, we included the largest NAFLD GWAS (8434 cases and 770,614 controls).

Results:
In univariable MR analysis, triglyceride levels were robustly associated with NAFLD risk (OR = 1.32, 95% CI=1.20-1.48, p=2.8e-7). In multivariable MR analysis, triglycerides remained robustly associated with NAFLD risk upon adjustment for other correlated lipoprotein subfraction (adjusted OR = 1.30, 95% CI = 1.12-1.51, p = 5.1e-4) (Figure). These results were consistent across a range of sensitivity analyses (MVMR-lasso, MVMR-Egger and MVMR-Median).

Conclusions:
Results of this two-sample MR study revealed that genetically predicted triglyceride levels may increase the risk of NAFLD independently of other lipoprotein subfraction. These results suggest that triglyceride lowering in the prevention of NAFLD might warrant further investigation.
Abstract 15710: Point-of-Care Ultrasonography: Artificial Intelligence in the Assessment of Left Ventricular Function
Authors: Motazedian Pouya , Marbach Jeffrey , Prosperi-Porta Graeme , Parlow Simon , Di Santo Pietro , Jung Richard , Abdel-Razek Omar , Bradford William , Tsang Miranda , Hyon Michael , Pacifici Stefano , Mohanty Sharanya , Huggins Gordon S , Simard Trevor , Hibbert Benjamin M
Published: June 2023

Introduction:
Point-of-care ultrasonography (PoCUS) has become routine for the bedside assessment of patients. Current evidence shows that image acquisition and interpretation of left ventricular function can be achieved reliably by trained users, but evidence is lacking for interpretation by artificial intelligence. We sought to evaluate the accuracy of PoCUS devices with integrated artificial intelligence in comparison to transthoracic echocardiograms for assessment of left ventricular ejection fraction (LVEF).

Methods:
This is a prospective, multicenter cohort study using the KOSMOS portable ultrasound device (EchoNous, Redmon, WA). PoCUS studies included an apical four and two chamber views and were obtained by either novice trainees or experienced ultrasonographers. A real-time, automated LVEF was calculated by the device using a modified Simpson’s method. These patients also underwent a formal transthoracic echocardiogram, with image acquisition and interpretation completed by blinded ultrasonographers and level-3 trained echocardiographers, respectively.

Results:
A total of 449 patients were enrolled in the study with 227 and 222 studies completed by novice and experienced scanners, respectively. Images of suitable quality were obtained in 208 of the novice cohort (91.6%) and 216 of the experienced cohort (97.3%). In comparison to formal echocardiography, linear regression shows a R
2
value of 0.82 for the total cohort, and 0.85 for the novice and 0.72 in experienced scanner subgroups. Incorporating an intra-observer variability of ± 5%, the sensitivity and specificity for an abnormal (≤50%) and severely reduced (≤30%) LVEF was 99.2% and 97.7%, and 86.8% and 99%, respectively.

Conclusions:
Our study is one first to assess the accuracy of PoCUS devices with integrated artificial intelligence. Based on our study, a real-time, automated LVEF can be acquired by PoCUS with strong correlation to formal echocardiography. This study also highlights that diagnostic quality studies can be acquired by novice scanners with comparable accuracy to experienced scanners. This provides evidence for an immediate and inexpensive method for accurate LVEF assessment in emergent and resource-limited environments.
Abstract 15714: Association of Obesity With Orthostatic Hypertension
Authors: Spadavecchia David , Dorairajan Smrita , sendra mauricio , Chockalingam Anand
Published: June 2023

Introduction:
Orthostatic hypertension (OHT) is variably defined, poorly understood, multifactorial but may contribute to target organ damage. Increase systolic blood pressure (SBP) over 10 mmHg from supine to standing may identify OHT with increased baseline sympathetic nervous system (SNS) and renin angiotensin aldosterone system (RAAS) activation. Diabetes, advanced age, and neurological disorders appear to predispose to OHT and this has not been characterized in obese patients.

Hypothesis:
RAAS and SNS activation is well recognized in obesity. Routine orthostatic BP measurement in obese patients may identify OHT.

Methods:
Between 5.2021 to 5.2022, we screened obese patients presenting to University of Missouri -Columbia cardiology clinic for OHT. Supine BP was obtained after 5 minutes of rest and standing BP measured 3 minutes after standing. BMI was estimated from height and weight obtained routinely during same clinic visit. Risk factors were estimated from medical records.

Results:
OHT was identified in 30 patients (Males 7, females 23) with average age 55.1 ± 17.6 years. Weight was 128.6 ± 27.4 kg, BMI 47.9 ± 9.9 kg/m
2
. Supine systolic and diastolic BP were 131.9 ± 15.9 and 78.3 ± 8.4 mmHg. On standing, systolic and diastolic BP increased to 155.7 ± 19.5 and 92.5 ± 13.1 mmHg. Standing resulted in systolic and diastolic BP increase of 23.8 and 14.2 mmHg, respectively. Hypertension (n= 23, 77%), depression (15, 50%) diabetes (12, 40%), asthma (9, 30%), sleep apnea (12, 40%), heart failure (7, 23%), anxiety - post traumatic stress disorder (5, 17%), chronic obstructive lung disease (3, 10%) and atrial fibrillation (3, 10%) were common associations. Acute increase in BP may contribute to palpitation and dyspnea on standing reported in 5 (17%) of the OHT patients.

Conclusions:
Orthostatic hypertension is prevalent in obese patients and underdiagnosed during clinic visits. Severe obesity predisposes especially women to significant standing blood pressure increase that may cause symptoms and target organ damage. Routine Orthostatic BP Screening during clinic visits especially in obese patients is required to identify orthostatic hypertension, to optimize outcomes with appropriate lifestyle interventions and medications.
Abstract 15718: Higher In-Hospital Mortality Among Cardiogenic Shock Patients With
De Novo
versus Acute on Chronic Heart Failure
Authors: Blumer Vanessa , Hernandez-Montfort Jaime , Sinha Shashank S , Kanwar Manreet , Garan Arthur Reshad , Zhang Yijing , LI BORUI , Baca Paulina , Dieng Fatou , Harwani Neil , Burkhoff Daniel , Kapur Navin K
Published: June 2023

Introduction:
Heart failure cardiogenic shock (HF-CS) constitutes a heterogenous population and has been identified as the leading type of shock among contemporary intensive care units. The in-hospital trajectory of shock severity and its association with mortality and transition to heart replacement therapy (HRT) or native heart survival (NHS) based on HF-CS phenotype has not been well described.

Methods:
The Cardiogenic Shock Working Group (CSWG) registry includes patients from 17 hospitals between 2016 and 2021. For this analysis, HF-CS patients were sub-classified as having
de novo
HF-CS or acute-on-chronic (ACHF) CS. In-hospital trajectories were assessed using baseline and maximum Society for Cardiovascular Angiography and Interventions (SCAI) stages and clinical outcomes were analyzed.

Results:
A total of 1,767 patients with HF-CS were included. Of these, 349 had
de novo
HF-CS (19.8%) and 1,371 (77.6%) had ACHF-CS. Overall, patients with
de novo
HF-CS had greater in-hospital death (32% vs 22%), NHS (58% vs 45%) and less HRT (33% vs 10%) when compared to ACHF-CS (all p<0.001). These variances in clinical outcomes differ when analyzed according to SCAI stages, with more significant differences between
de novo
HF-CS vs. ACHF-CS across baseline and maximum SCAI Stages C-D
(Figure).

Conclusions:
Using a large contemporary real-world dataset of HF-CS, we identified that
de novo
HF-CS is associated with higher in-hospital mortality and NHS and lower HRT compared to ACHF-CS. These differences vary depending to SCAI Stage and are more pronounced in SCAI Stages C and D. Further efforts to define shock trajectories and to tailor therapeutics in HF-CS patients are urgently needed.
Abstract 15721: Gender Differences in Temporal Trends and Outcomes of Pulmonary Arterial Hypertension-Related Hospitalizations in the US
Authors: Olanipekun Titilope , Abe Temidayo , Udongwo Ndausung , Effoe Valery S
Published: June 2023

Introduction:
There is limited data on the gender differences in the trend of hospitalizations related to PAH and associated outcomes in the US

Methods:
We queried the National Inpatient Sample from 2010 to 2019 to identify PAH admissions using international classification of diseases (ICD) codes 416.0 (ICD-9) and I27.0 (ICD-10)

Results:
20,513 hospitalizations with PAH as the primary diagnosis was analyzed during the study period. There were 13,928 women (67.9%) and 6,584 (32.1%) men. The mean age among women (SD) and men (SD) were 66 years (16) and 65 years (17) respectively. Between 2010 and 2019, PAH hospitalization rates declined in both women (13.5% vs. 8.5%], P < 0.001) and men (14.2% vs. 8.3%, P = 0.027. The overall mortality rate was higher in men compared with women (6.6% vs. 5.7%, P = 0.015. Though crude mortality rates declined for the total population, this was statistically significant only among women (6.7% vs.5.6%, P = 0.011). On adjusted multivariate analysis, factors associated with increased odds of inpatient mortality among women were age 45 - 64 years (OR 1.62, 95% CI 1.11 - 2.37, P = 0.013) and > 65 years (OR 2.36, 95% CI 1.57 - 3.55, P<0.001) compared with age 18-44 years. Black (OR 1.44, 95% CI 1. 13 - 1.78, P < 0.001) and Hispanic race/ethnicity (OR 1.06, 95% CI 1.02 - 1.51, P = 0.037), compared with White race/ethnicity. Comorbidities and in-hospital complications associated with increased mortality were chronic kidney disease, acute pulmonary embolism (PE), and acute respiratory failure (ARF). Among men, age > 65 years (OR 3.28, 95% CI 1.68 - 6.41, P = 0.001), Black (OR 1.9, 95% CI 1.36 - 2.91, p < 0.001) and Hispanic race/ethnicity (OR 1.21, 95% CI 1.08 - 1.78, P = 0.021), compared with White race/ethnicity were associated with increased odds of mortality. The presence of congestive heart failure and complications of acute PE, ARF, acute ischemic stroke, and atrial fibrillation were also associated with increased mortality.

Conclusions:
From 2010 to 2019 in the US, PAH-related hospitalization rates decreased in both women and men while mortality only decreased among women. Men were more likely to die during hospitalization compared with women. Older age and Black and Hispanic race/ethnicity were associated with higher mortality in both women and men.
Abstract 15751: Trends and Disparities in Pulmonary Arterial Hypertension Over the Past Decade: A National Inpatient Sample Database Study
Authors: Sana Muhammad Khawar , ASEMOTA IRIAGBONSE , Park Dae Yong , Hammo Hasan , Yilmaz Mahir , Murthi Mukunthan , Sharma Bharosa , Shaka Hafeez
Published: June 2023

Introduction:
Pulmonary arterial hypertension (PAH) is well defined, however, the trends and disparities have not been studied recently after the update in guidelines.

Methods:
We utilized National Inpatient Sample Database 2010-2019 to identify the cohort with principal diagnosis of PAH using ICD-9 and 10 codes. Primary outcome analysis included the crude admission rate of PAH per 1,000,000 adult hospitalizations during each calendar year stratified by sex, race, and median household income (MHOI). Secondary outcome analysis included trends in inpatient mortality rate, mean length of hospital stay (LOS), and mean total hospital charges (THC).

Results:
There were a total of 341 million admissions from 2010-2019 out of which 0.004% (13644) were adults admitted with principal diagnosis of PAH. There was no significant difference in year on year admissions in the last decade (Figure). Most patients were aged 18-65 when diagnosed (OR 1.73, 95% CI 1.55-1.92). Females were twice as likely to be diagnosed with PAH than males (OR 2.40, 95% CI 2.17-2.64). African Americans (OR 1.35, 95% CI 1.21-1.50) and Asian/Pacific Islander (OR 1.22, 95% CI 1.04-1.42) were at slightly more risk of PAH. There was no significant difference in inpatient mortality among patients with principal diagnosis of PAH over the last decade. Although mortality increased with increasing age (OR 1.29. 95% CI 1.29-3.33 for age > 65) (OR 1.79, 95% CI 1.45-2.77) but did not defer when stratified for gender , race or year.

Conclusion:
Admissions for principal diagnosis of pulmonary arterial hypertension have remained unchanged over the last decade. Female sex, age and median house hold income is associated with increased risk for PAH.
Abstract 15768: Relative Longitudinal Strain Apical Sparing Pattern as a Detrimental Factor of Cardiovascular Outcome After Transcatheter Aortic Valve Replacement
Authors: Liu Dan , hu kai , Lau Kolja , Müntze Jonas , Maniuc Octavian , Nordbeck Peter
Published: June 2023

Introduction:
Several risk scores have been developed for outcome after heart surgery. However, risk factors associated with clinical outcome in patients undergoing transcatheter aortic valve replacement (TAVR) are still not well defined. This study aimed to determine laboratory and echocardiography determinants of short- and long-term outcome after TAVR.

Methods:
This retrospective study comprised 598 consecutive patients with sole aortic stenoseis (AS) who received balloon-expandable TAVR in our hospital (mean age 81.7±5.7 years, 48.7% male, median EuroSCORE II 5.0%). Pre-operative laboratory and imaging data including speckle-tracking echocardiography were analyzed. Clinical outcomes included cardiovascular (CV) death, CV hospitalization, and procedure related complications at 30 days, 1 year, and at 2 years after TAVR.

Results:
Semi-quantitative assessment defined as ≥3 LV wall segments with the apico-basal LS ratio >3.0 was used to define relative apical sparing pattern (RASP). The prevalence of RASP was 19.2%. RASP patients had higher prevalence of acute kidney injury (AKI, 10.4% vs. 3.3%, P=0.001) and new-onset left bundle branch block (LBBB) after TAVR (17.4% vs. 6.8%, P<0.001). CV mortality at 30 days (7.0% vs. 3.1%, P=0.062), 1 year (15.7% vs. 7.9%, P=0.010), and 2 years (22.6% vs. 9.9%, P<0.001) was also higher after TAVR. RASP remained the strongest determinant for AKI (OR=3.11, P=0.007), new-onset LBBB (OR=2.89, P<0.001), increased 30-day CV related hospitalization or death risk (OR=2.20, P=0.033). Lower albumin level and RASP were identified as independent determinants of increased 1-year and 2-year CV mortality risk (RASP: HR=1.83 and 2.18, P=0.039 and 0.002; albumin<4.0g/dl: HR=3.18 and 2.55, both P<0.001), regardless of TAVR approach and EuroSCORE II. After adjustment, the addition of RASP significantly improved prognostic power of a model including clinical variables and low albumin level for predicting CV death at 2-year follow-up (
χ
2
from 28.18 to 40.70, P=0.001).

Conclusions:
RASP represents a novel clinically relevant determinant of outcome after TAVR. Low albumin and RASP were identified as the strongest laboratory and echocardiography determinants for increased short- and long-term outcome after TAVR.
Abstract 15779: Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Neurons as Models for
Toxoplasma Gondii
Infection
Authors: Ting Li-Min , yang jiajia , Burgos Angulo Mariana , McDonald Thomas V , Kim Kami
Published: June 2023

Introduction:
Toxoplasma gondii
infects all nucleated cells in warm-blooded vertebrates. Infection may be asymptomatic in healthy people but may result in the lifelong chronic persistence of cysts containing bradyzoites in specific tissues such as muscle and neurons.

Hypothesis:
Stem cell-derived neurons and cardiomyocytes will recapitulate the tissue-specific parasite-host interaction underlying chronic persistence in
Toxoplasma
infection.

Methods:
Human induced pluripotent stem cell-derived cardiomyocytes (iCMs), cardiac fibroblasts (iCFs) and neurons (iNEs) were used as biologically relevant models to study the interactions of
T. gondii
with human hosts
in vitro
. iCM, iCF and iNE were infected with
T. gondii
TypeI/III EGS strain (dual fluorescent stage-specific reporter strain: mCherry driven by SAG1 promoter and sfGFP driven by the LDH2 promoter).

Results:
We observed higher rate of bradyzoite formation in iCM and iNE, compared to iCF from the same donor at 72 hours post-infection by fluorescence microscopy of live cells and flow cytometry. Furthermore, we have analyzed the changes in the gene expression of host cells during
Toxoplasma
infection using high-throughput RNA-seq. Compared to uninfected iCMs, iCMs infected for 24 hours showed 1090 upregulated and 753 downregulated differentially expressed genes (DEGs); iCMs infected for 72 hours showed 1956 upregulated and 1253 downregulated DEGs. Compared to uninfected iCFs, iCFs infected for 24 hours showed 1654 upregulated and 1971 downregulated DEGs; iCFs infected for 72 hours showed 2742 upregulated and 1916 downregulated DEGs. In comparison to uninfected iNEs, iNEs infected for 24 hours showed 190 upregulated and 321 downregulated DEGs; iNEs infected for 72 hours showed 244 upregulated and 91 downregulated DEGs. Enrichment analysis of gene sets regulated by infection will be presented.

Conclusions:
Our
in vitro
generated human iCMs, iCF and iNEs have provided us a valuable tool for better understanding the impact on the host cells during
Toxoplasma
infection. A detailed analysis of validation and intervention of the top dysregulated genes in all different cell types will inform the design of potential therapeutic targets.
Abstract 15795: Connections Between the Western Diet and Inflammation in Heart Failure
Authors: Davis Erica , Dunbar Sandra B , Higgins Melinda , Wood Kathryn A , Morris Alanna A , Butts Brittany
Published: June 2023

Introduction:
The Western Diet (WD) is associated with deleterious processes linked with chronic disease and may play a role in the pathophysiology of heart failure (HF). Trimethylamine-N-oxide (TMAO) is a diet-linked metabolite that contributes to inflammation and is associated with higher TNF-α, especially in HF populations. The dietary inflammatory index (DII) score measures the inflammatory potential of a diet and the inflammatory effects of foods. More studies are needed to determine how the WD impacts immunological pathways and cytokines in the context of clinical and population characteristics.

Purpose:
The aim of this study was to explore associations between the WD, DII, TMAO, and TNF-α in Black patients living with HF.

Methods:
Thirty Black participants (mean age 55.3, 67.7% women) with HF were included in this study. TMAO and TNF-α levels were analyzed from dried blood spots using immunoassays. Participants completed a Food Frequency Questionnaire (FFQ) from which a DII score was derived. Food groups and nutrients, like choline, were measured with the FFQ. Sociodemographic variables were measured. Analyses included correlational and inferential statistics.

Results:
Mean DII score was -.38 revealing an overall anti-inflammatory diet with higher inflammatory scores among men (-.23) as compared to women (-.43). Women consumed greater kilocalories with more saturated fat, sodium, dairy, sugar, and fruit while men consumed more cholesterol, choline, proteins, alcohol, legumes, poultry, red meats, eggs, and phosphatidylcholine. DII score was negatively correlated with dietary choline (r= -.73, p<.001), but did not correlate with TMAO or TNF-α. TNF-α and TMAO were positively related (r=.30, p=.057).

Conclusions:
This sample of well-educated HF patients from a busy HF referral center did not consume a highly pro-inflammatory diet, yet our findings provide insight for specific food groups such as those with choline. In patients with HF, it is important to monitor intake of inflammatory foods and appreciate that increasing age may play a role in the retention of dietary metabolites. Further study of these relationships in patients with HF could lead to tailored dietary educational interventions based on dietary patterns, age, and cultural relevance.
Abstract 15808: Frequency and Impact of Repeat Transthoracic Echocardiography in Inpatients Transferred for Transcatheter Aortic Valve Replacement
Authors: Nardi Matthew , Weiner Rory B
Published: June 2023

Introduction:
Appropriate ordering of cardiac imaging is an important factor in optimizing cardiac testing and resource utilization. Echocardiography is frequently repeated when patients are transferred from one hospital facility to another. This single-center retrospective study aimed at assessing the frequency of repeat transthoracic echocardiography (TTE) and its clinical implications prior to non-elective transcatheter aortic valve replacement (TAVR) in patients transferred from referring hospitals.

Methods:
During a 2-year period there were 62 patients (32 male; mean age 79.8
+
9.4 yrs) transferred from referring hospitals to an academic referral hospital for non-elective TAVR.. All patients had a TTE performed prior to transfer. Patients were grouped based on whether the accepting hospital performed a repeat TTE prior to the TAVR procedure during the index admission. Values for left ventricular ejection fraction (LVEF), calculated aortic valve area, mean aortic valve (AV) gradient, and peak aortic valve gradient were compared between the outside and accepting hospital TTE reports.

Results:
Of the 62 hospital transfers, 34 (54.8%) had a repeat TTE performed by the accepting hospital. Average time waiting for a repeat TTE was 2.3
+
1.5 days. Measurements of LVEF (48.8%
+
14.5 vs 51.7
+
16.2 [P=0.44]), aortic valve area (0.7
+
0.2 vs 0.7
+
0.2 [P=0.53]), mean AV gradient (46.2
+
18.7 vs 45.1
+
14.8 [P=0.78]) and peak AV gradient (76.2
+
31.3 vs 74.9
+
23.3 [P=0.86]) among patients who had a repeat TTE performed by the accepting hospital were not statistically different than values obtained at the referring hospitals.

Conclusions:
Patients transferred to an academic referral center for TAVR had repeat TTE performed more than half of the time. Our data indicate that key echocardiographic parameters (LVEF, aortic valve area, and AV gradients) were not different between the TTEs at the referring and accepting hospitals. It is possible that improved digital efforts at image sharing across hospitals may obviate the need for repeat cardiac imaging and improve efficiency of care. Such efforts may impact hospital length of stay and cost, and warrants further study on a larger scale.
Abstract 15833: Impact of Sex on Outcomes Following Aerobic Exercise Training in Patients With Symptomatic Atrial Fibrillation
Authors: Elliott Adrian D , Verdicchio Christian , Mahajan Rajiv , Middeldorp Melissa E , Gallagher Celine , Lau Dennis H , Sanders Prashanthan
Published: June 2023

Introduction:
Aerobic exercise prescription may promote maintenance of sinus rhythm in patients with atrial fibrillation (AF). Very little data exists on whether this may be modified by patient sex.

Hypothesis:
Male and female patients with AF would benefit from exercise prescription.

Methods:
This study was a prospective, randomized, controlled trial of patients with symptomatic paroxysmal or persistent AF, referred for consideration of AF ablation. Randomization was 1:1 to either aerobic exercise intervention or usual medical care for a period of 6 months with a further 6 months follow-up. The exercise intervention was delivered in a hybrid format of weekly supervised exercise sessions coupled with prescribed home exercise, up to a total of 210 minutes per week. The intervention was led by a clinical exercise physiologist. Management of arrhythmia was at the discretion of a cardiologist blinded to patient randomization. The primary endpoint reported here is recurrent AF without rhythm control strategies.

Results:
Of the 120 patients enrolled in the study (Aged 65±10, BMI 30±6, 38% Persistent AF), 51 were female (42.5%). Female patients were less likely to have persistent AF at baseline (19.6%) compared to males (47.8%), had comparable BMI (30.8 v 30.2 kg/m
2
), were older (68±7 v 63±11 years) and had lower baseline peak oxygen uptake (16±4 v 23±5mL/kg/min, p<0.001). After 12-mnths of follow-up, both male (HR 0.52, 95% CI: 0.29-0.91, p=0.02) and female patients (HR 0.47, 95% CI: 0.23-0.95) in the exercise group had reduced recurrence of AF without anti-arrhythmic medication or AF ablation.

Conclusions:
Despite baseline differences in risk factor profile, aerobic exercise training is equally effective in males and females for the reduction of recurrent arrhythmia amongst patients with symptomatic atrial fibrillation. Exercise-based intervention should be recommended to patients of both sex, to promote the maintenance of sinus rhythm.
Abstract 15842: Interplay of Genomic and Conventional Risk for Cardiometabolic Disease in Saudi Arabia
Authors: Shim Injeong , Kuwahara Hiroyuki , Chen NingNing , Hashem Mais , AlAbdi Lama , Gao Xin , AbouElHoda Mohamed , Won Hong-Hee , Natarajan Pradeep , Ellinor Patrick T , Khera Amit V , Alkuraya Fowzan S , FAHED AKL C
Published: June 2023

Introduction:
Saudi Arabia is the largest country in the Middle East and has an alarming rise in cardiometabolic disease. While conventional risk factors are highly prevalent, it is not clear if and how genomic risk might be playing a role.

Methods:
In 5,399 Saudi patients (age 54.8±14.8 years, 35.7% female) referred for cardiac catheterization, we collected detailed cardiometabolic phenotype data and performed whole-genome genotyping. We implemented a computational framework to develop Arab-specific polygenic scores for 9 traits (Figure A, B). We studied the association of the polygenic scores with cardiometabolic disease, and their interplay with conventional risk factors using regression models adjusted for age, sex, and genetic ancestry.

Results:
Within this disease cohort with high prevalence of conventional risk factors - 65.0% coronary artery disease (CAD), 55.6% type 2 diabetes (DM-2), 41.5% obesity, 48.8% hypercholesterolemia, 80.6% hypertension, and 38.3% smoking - polygenic scores were strongly associated with cardiometabolic traits (Figure C). The effect sizes of polygenic scores for CAD and DM-2 remained unchanged with adjustment for clinical risk factors. Genomic risk was also associated with the severity of CAD, as measured by the number of vessels with severe stenosis on cardiac catheterization (Figure D). CAD patients with high genomic risk - defined as top quintile of the polygenic score - (N=568) had earlier onset (54.8 vs. 57.9 years, p=0.001) and more severe disease (41.3% vs. 29.9% with three-vessel CAD, p<0.001) despite similar clinical risk factors, compared to CAD patients without high genomic risk (N=1144).

Conclusions:
Polygenic scores were strongly associated with cardiometabolic disease even in a non-European population with high prevalence of conventional risk factors. Genomic risk for CAD appears independent of conventional risk factors and identifies patients with earlier onset and more severe disease.
Abstract 15879: Impact of Pulmonary Hypertension on In-Hospital Outcomes for Patients Undergoing Typical Atrial Flutter Ablation
Authors: Murthi Mukunthan , Vardar Ufuk , Atluri Ramtej , Park Dae Yong , Shahi Anoj
Published: June 2023

Introduction:
Pulmonary hypertension (PHT) is a progressive disease with a clinical course characterized by frequent decompensations in advanced stages. Atrial arrhythmias, including typical atrial flutter, are common in patients with PHT. We sought to investigate the effect of presence of pulmonary hypertension to the outcomes after typical atrial flutter ablation.

Methods:
We utilized the National Inpatient database from 2016 to 2019 to perform this study. By utilizing the ICD-10-CM codes all hospitalizations for typical atrial flutter ablation were identified. Patients with atypical flutter and ablation were excluded. Among these subjects, those with associated diagnosis of pulmonary hypertension (WHO Group 1 to 5) were identified and they formed the study group. Primary outcome was to in-hospital mortality and complications. Secondary outcomes included analysis of patient clinical characteristics, length of hospital stay (LOS) and total hospital charges (TOTCH). Multivariate regression analysis was used to predict outcomes.

Results:
A total of 7,784 patients with PHT were hospitalized for typical atrial flutter ablation during the study period. Patients with PHT were slightly older (66 vs 67 years, p<0.001). The proportion of males was lower in the PHT group (57vs 67 %, p<0.001). For Typical AFL patients undergoing ablation, the presence of PHT was associated with higher odds of mortality (a0R= 1.8, p=0.003), acute kidney injury (a0R= 1.6, p<0.001), heart failure exacerbation (a0R= 1.3, p<0.001) and cardiogenic shock (a0R= 2.2, p<0.001) on multivariate regression analysis. They also had higher LOS (+2.3 days, p<0.001) and TOTCH (+$30,501, p<0.001).

Conclusion:
Our data shows that pulmonary hypertension is independently associated with worse in-hospital outcomes in patients undergoing typical atrial flutter ablation, including higher mortality. Further prospective studies are required to confirm our findings.
Abstract 15915: Ultrasound Targeted Microbubble Cavitation-Induced Endothelial Hyperpermeability is Calcium-Dependent and Regulated by Enos Signaling
Authors: Paranjape Anurag N , Chen Xucai , Villanueva Flordeliza S
Published: June 2023

Introduction:
Ultrasound (
US
)-targeted microbubble (
MB
) cavitation (
UTMC
) facilitates delivery of cell-impermeant drugs across the endothelial barrier; mechanisms are poorly understood. We reported that UTMC causes inter-endothelial gaps in cultured endothelial cell (
EC
) monolayers, which could increase barrier permeability, and that UTMC increases Ca
2+
influx into ECs. Given that increased intracellular Ca
2+
activates eNOS, and nitric oxide (NO) release promotes microvascular permeability, we hypothesized that UTMC increases intracellular Ca
2+
through activation of mechanosensitive Piezo-1 Ca
2+
channels, leading to NO synthesis and endothelial barrier hyperpermeability.

Methods:
Transwells were endothelialized with human coronary artery ECs. Lipid MBs were added, and US was delivered for 10 s (1 MHz, 250 kPa, 10 cycles, 10 ms interval). Permeability was measured using dextran transfer and transendothelial electrical resistance (
TEER
). GsMTx4 and L-NAME were used to inhibit Piezo1 and eNOS, respectively; Fluo-4 AM to visualize Ca
2+
influx; DAF-FM to detect NO. S-nitrosylation was measured with biotin switch assay.

Results:
UTMC reduced TEER (1.7 fold,
p<0.05
) and increased dextran flux across the transwell (2-fold,
p<0.01
for 70 kDa dextran, 1.6 fold,
p<0.05
for 10 kDa dextran), which was abrogated by L-NAME. UTMC significantly increased Ca
2+
influx into ECs and tripled NO (
p<0.05
), but these increases and UTMC-mediated hyperpermeability were blunted by Piezo1 channel inhibition (
p<0.0001)
. UTMC increased S-nitrosylation of proteins (1.7 fold,
p<0.01
) and was associated with s-nitrosylation of VE-cadherin, its redistribution into focal adhesion junctions, and increased stress fiber formation, which were abolished by L-NAME.

Conclusions:
UTMC causes endothelial barrier hyperpermeability through a Ca
2+
-dependent mechanism, where Ca
2+
influx into ECs, mediated in part by mechanosensitive Piezo1 channels, modulates eNOS signaling. Our data suggest that eNOS regulates UTMC-induced hyperpermeability, possibly through s-nitrosylation of VE-cadherin. Further studies to examine mechanisms regulating UTMC bioeffects will aid in clinical translation and optimization of UTMC for delivery of cell-impermeant drugs.
Abstract 15922: Effect of Glp-1 Receptor Agonists on Systolic Blood Pressure in Patients With Overweight or Obesity: A Network Meta-Analysis
Authors: Usman Muhammad Shariq S , Siddiqi Tariq J , Siddiqui Asad Ali , Ali Abraish , Shahid Izza
Published: June 2023

Introduction:
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to reduce weight in patients with overweight or obesity. However, their effect on systolic blood pressure (SBP) remains less well-established. We conducted a network meta-analysis to evaluate the effect of different drug-dose combinations of GLP-1 RAs on SBP in this population.

Methods:
Electronic databases were searched through January 2022 for RCTs which evaluated the efficacy of different doses of semaglutide, liraglutide, efpeglenatide, and exenatide in obese patients with and without T2DM. Systolic blood pressure (SBP) was chosen as the primary endpoint. A frequentist network meta-analysis using random-effects model was conducted, and pooled estimates were reported as mean differences (MD) with 95% confidence intervals (CI).

Results:
A total of 20 RCTs were included in the analysis. Among individuals with T2DM, liraglutide <2 mg once daily (QD) showed the greatest reduction in SBP (MD: -3.78 [-5.63; -1.15]), followed by exenatide 10 ug twice daily (BID) (MD: -3.39 [-5.63; -1.15]), and semaglutide ≥1mg once weekly (QW) (MD: -3.28 [–5.68; –0.88]), when compared with placebo. Among individuals without diabetes, efpeglenatide ≤ 6 mg QW showed the greatest reduction in SBP (MD: -6.00 [-9.89; -2.11]), followed by semaglutide ≥ 1 mg QW (MD: -4.54 [–5.69; –3.39]), and semaglutide <1mg QW (MD: -4.51 [–5.49; –3.54]). The figure shows how each drug/dose combination compares with others.

Conclusions:
This network meta-analysis suggests liraglutide <2mg QD is the most efficacious GLP-1 RA in lowering SBP in obese patients with T2DM. For obese patients without diabetes, efpeglenatide ≤6mg QW is the most effective.
Abstract 160: Associations Between Markers Of Inflammation And Myocardial Injury In Out-of-hospital Cardiac Arrest Patients After Treatment With Tocilizumab - A Sub Study Of The IMICA Trial
Authors: Meyer Martin A , Wiberg Sebastian , Grand Johannes , Obling Laust E , Kjaergaard Jesper , Hassager Christian
Published: June 2023

Background:
Systemic inflammation is a major component of the post-cardiac arrest syndrome. Treatment with tocilizumab, an interleukin 6 receptor antagonist, was shown in the IMICA trial to reduces systemic inflammation and markers of myocardial injury in comatose resuscitated out-of-hospital cardiac arrest (OHCA) patients. This was demonstrated by lower levels of the markers of inflammation, CRP, and leukocytes, as well as the marker of myocardial injury, Troponin T (TnT), in patients treated with tocilizumab compared to placebo. OBJECTIVE: To investigate associations between markers of inflammation and myocardial injury in the IMICA trial.

Methods:
At admission, 80 OHCA patients were randomized to either tocilizumab or placebo (NCT03863015). Area under the curve (AUC) between 0-72 hours was calculated for leukocyte count, CRP, and TnT. Spearman’s correlation analyses were performed after log2 transformation.

Results:
AUC of leukocytes correlated positively with TnT in both treatment arms (tocilizumab: r=0.4, p=0.03; placebo: r=0.4, p=0.02; see figure). Also, a positive correlation between AUC of CRP and TnT was found in patients treated with tocilizumab but not in patients receiving placebo (tocilizumab: r=0.3, p=0.03; placebo: r<0.1 p=0.86).

Conclusions:
These findings illustrate that in general, patients with lower levels of leukocytes also had lower levels of myocardial injury. The correlation between CRP and TnT in the tocilizumab group could possibly reflect response to treatment, or baseline activity prior to treatment. Modulation of inflammation could have cardioprotective as well as systemic effects, both of which could be possible mechanisms for the reductions in biomarkers of myocardial injury as previously reported in this trial. However, correlation does not necessarily imply causality and it is possible that other, yet uninvestigated mechanisms are responsible for the observed effects of tocilizumab.
Abstract 167: Nasal Sensor Capnographic Differences In Major Traumatic Brain Injury Patients Receiving Non-rebreather Mask Versus Nasal Cannula Oxygen Delivery
Authors: Barnhart Bruce J , Spaite Daniel W , Jorgenson Dawn B , Seiver Adam , Helfenbein Eric D , Gaither Joshua B , Rice Amber D , Keim Samuel M , Hu Chengcheng
Published: June 2023

Background:
The advent of highly sensitive End-Tidal CO2 (ETCO2) sensors allows effective monitoring of intubated patients in EMS. Previous work has explored the use of ETCO2 monitoring in non-intubated patients with sensors placed in the nares. However, little is known about the effect of passive O2 delivery [nasal cannula (NC) or high-flow, non-rebreather mask (NRB)] on ETCO2 measurement.

Objective:
To compare ETCO2 measurements in non-intubated Traumatic Brain Injury (TBI) patients receiving O2 via NC vs. NRB in the field.

Methods:
A subset of cases from the EPIC EMS TBI Study (NIH-1R01NS071049) were evaluated (4/13-4/18). Non-intubated cases from 5 EMS agencies providing monitor data, including continuous ETCO2. Start and end segments were excluded to remove artifact from initiation (“ramp-up”) or termination of monitoring.
Statistics:
Wilcoxon rank-sum test, two-sample t-test, and Chi-squared test were used as appropriate. Linear regression compared continuous variables in adjusted analyses (α = 0.05).

Results:
Included were 151 cases [median age: 52 (range: 9-91; 66% male)]. Of those, 62 (41%) received NCO2 and 89 (59%) via NRB. Patient-level mean ETCO2 was slightly lower in the NC group (mean = 26.9 mmHg; SD 6.7) compared to NRB (mean 30.2; SD 8.1; p=0.007). Differences in the mean were: Unadjusted: 3.3 (95% CI 0.9-5.7); Adjusted 2.7 (0.2-5.2). There were no significant differences in means of the patient-level lowest or highest recorded values.

Conclusion:
While there was a statistically lower ETCO2 in the NC versus NRB-oxygenated patients, it was around 3 mmHg and, thus, not clinically significant. This is surprising since: 1) the O2 flow rates and 2) the open-air (NC) versus mask (NRB) delivery methods are so dramatically different. Future study is needed to identify the clinical implications of using noninvasive ETCO2 measurement as a tool for monitoring ventilatory status and changes in non-intubated TBI (and other) patients in emergency settings.
Abstract 181: In-hospital Cardiac Arrest Debrief In A Pediatric Intensive Care Unit
Authors: Joyner Benny , Pirzadeh Afsaneh , Seaman Christen , Pizzuto Matthew
Published: June 2023

Background:
Debrief of in-hospital cardiac arrests (IHCA) has been shown to improve outcomes. There can be limited data available to quantitatively review a resuscitation, but careful analysis can provide insight for improvement.

Methods:
A standard process for debriefing all cardiac arrests was developed in our institution’s pediatric intensive care unit (PICU). Characteristics of the event were documented, and each arrest was independently reviewed by a lead arrest review investigator including telemetry data, chart review, and provider interviews when available. Data was stored in a secure redcap database.

Results:
From April 1, 2021 to March 31, 2022 there were n=25 IHCAs in 22 patients. Eighteen (72%) were classified as severe bradycardia with hypotension and/or poor perfusion; 6 (24%) were pulseless electrical activity; and 1 was unstable VT/VF. Two patients had a shockable rhythm during their arrest. The median arrest duration was 6 minutes with the longest duration being 104 minutes. Out of the 25 arrests, 18 (72%) had return of spontaneous circulation. Out of the 22 patients who had at least 1 arrest, 9 (41%) survived to hospital discharge and 12 (55%) died; 1 patient is still admitted. In addition to outcomes data, the debrief process led to many process improvements including the utility of a backboard (Figure 1A) and use of the respiratory rate tracing (thoracic impedance) in assessing compressions (Figure 1B).

Discussion:
IHCA in pediatric patients confers a significant risk of mortality and morbidity. Development of a comprehensive debrief process will help to identify areas for improvement in all facets of arrest care.
Abstract 193: Leading Causes Of Traumatic Cardiac Arrest In The United States: National-level Surveillance
Authors: Shekhar Aditya C
Published: June 2023

Introduction:
Out-of-hospital cardiac arrest secondary to traumatic injury is associated with extremely poor survival, even when compared with other etiologies of cardiac arrest. Traumatic cardiac arrest is extremely preventable if the original injury causing the arrest can be prevented.

Hypothesis:
From a public health standpoint, there is an urgent need to identify the specific causes of traumatic cardiac arrest with the hopes of specifically targeting prevention efforts. Because they are the first responders to all types of out-of-hospital cardiac arrest, data from the emergency medical services (EMS) perspective may be invaluable in this effort.

Methods:
In order to provide a broad, descriptive overview of the causes of traumatic cardiac arrest in the United States, we examined a national-level database of EMS runs in the United States (NEMSIS). This database is populated directly from information entered in EMS patient care reports by more than ten-thousand EMS agencies, allowing us to provide a nationally-representative description of cardiac arrest trends. We examined traumatic cardiac arrests responded to by EMS between January 2017 and December 2021 where EMS documented the primary mechanism of injury.

Results:
A total of 70,712 traumatic cardiac arrests met inclusion criteria. There were significantly more male patients (78%) than female patients (22%). A majority (73%) were in patients between 18 and 65 years of age; 20% involved patients older than 65 years and 7% involved patients under 18 years. Across both sexes and all age groups, the two common arrest causes were crash-related injuries (36%) and firearm-related injuries (28%). However, compared with other age groups, arrests in elderly patients were more likely to be caused by intentional self-harm and, compared with female patients, arrests in male patients were more likely to be caused by assault.

Conclusions:
Our results offer important preliminary surveillance on the causes of traumatic cardiac arrest in the United States. These results can hopefully lay the foundation for important public health efforts aimed at preventing cardiac arrest and mortality from traumatic injury; crashes and firearms may represent two foci of interest.
Abstract 196: Association Between Continuous Carotid Blow Flow And Continuous Cerebral Perfusion Indexes Assessment By NIRS In A Porcine Model Of Ventricular Fibrillation During CPR
Authors: Kiguchi Takeyuki , NISHIOKA NORIHIRO , Makino Yuto , Olivari Davide , Giorgio Daria D , Koyama Yasuaki , Matsuyama Tasuku , Kamo Wataru , Kamada tsuyoshi , Maeda Hideki , Ristagno Giuseppe , Iwami Taku
Published: June 2023

[Background]:
Maintenance of cerebral blood flow during cardiopulmonary resuscitation (CPR) is a critical factor affecting the neurological outcome of patients after cardiac arrest. However, dynamic indicator of cerebral blood flow during CPR is not established. Near infrared spectroscopy (NIRS) is a non-invasive technique capable of detecting changes in cerebral blood volume continuously. The aim of this study is to compare cerebral perfusion during CPR obtained by continuous measure of carotid blow flow (CBF) using flow sensor with continuous cerebral perfusion indices (CPI) assessment by NIRS in a porcine model of ventricular fibrillation (VF) cardiac arrest.

[Methods]:
CBF during CPR were measured in 21 swine (25± 3 kg) using extra-vascular flow probes positioned around the common carotid arteries. The optodes of the NIRS were attached to the skull bone. Following baseline measurements, VF was electrically induced. After the interval of untreated VF, CPR was continued for 25 min, during which mechanical and manual CPR was alternated at every 5 min intervals. CBF and CPI were measured continuously during CPR. The mean volume of CBF and CPI was calculated average 10 beats in each phase. Correlations between CBF volume and CPI were analyzed by Spearman's rank correlation.

[Results]:
The followability of CBF and CPI during CPR was good. The Spearman's rank correlation coefficient between CBF volume and CPI was different by sections and it was suggested that the CBF volume was too small to assess the correlation in many sections. If the sections with CBF volume>0.4 ml were extracted and reanalyzed, the rate of sections correlated between CBF volume and CPI were increased (Spearman’s correlation coefficient≧0.4 was 41.3%, Spearman’s correlation coefficient≧0.7 was 17.5%).(Table)

[Conclusions]:
It was suggested that CPI by NIRS can reflect the CBF during CPR in the sections where enough CBF is.
Abstract 231: Volume And Direction Of Carotid Blood Flow During Cardiopulmonary Resuscitation In A Porcine Model Of Ventricular Fibrillation
Authors: NISHIOKA NORIHIRO , Kiguchi Takeyuki , Makino Yuto , Fumagalli Francesca , Magliocca Aurora , Koyama Yasuaki , Matsuyama Tasuku , Kamo Wataru , Kamada tsuyoshi , Maeda Hideki , Ristagno Giuseppe , Iwami Taku
Published: June 2023

Introduction:
Hemodynamics during cardiopulmonary resuscitation (CPR) is not well understood. We aimed to quantitatively evaluate the volume and direction of carotid blood flow (CBF) during CPR in a porcine model of ventricular fibrillation (VF) cardiac arrest.

Methods:
Nineteen male domestic pigs were intubated and ventilated mechanically. Following baseline measurements, VF was electrically induced. CBF was measured continuously using a flow probe positioned around the common carotid arteries. After 0 or 5 min no-flow time of untreated VF, CPR was initiated, involving chest compressions and ventilation with oxygen. CPR was continued for 25 min, with mechanical (L1, L2, and L3) and manual (M1 and M2) CPR alternated at 5 min intervals. A Friedman test was used to compare the groups in each phase. Post hoc analysis was performed using a Wilcoxon signed-rank test (Bonferroni corrected).

Results:
CBF was calculated as the average of each phase. The net flow was calculated through subtracting the retrograde flow from the anterograde flow. Average net flow (median, interquartile range [IQR], mL/min) during CPR was 58.1 (24.0-111.3), 19.8 (8.4-24.9), 21.2 (9.5-37.9), 15.4 (8.4-24.9), and 16.4 (10.3-30.1) in phases L1, M1, L2, M2, and L3, respectively (
p
< 0.001, L1 vs. M1). The ratio (median, IQR, %) of retrograde to anterograde flow was 41.3 (16.7-58.7), 48.6 (33.1-60.4), 42.2 (36.5-76.4), 49.1 (39.4-68.5), and 50.0 (38.0-79.0) in phases L1, M1, L2, M2, and L3, respectively (
p
= 0.299).

Conclusions:
In this VF cardiac arrest model, the net flow of the carotid artery during CPR decreased with time. Both mechanical and manual CPR produced substantial retrograde flow, although the ratio of retrograde to anterograde flow did not change.