bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 152: Effect Of Calcium On Patient Outcomes In Pulseless Electrical Activity With Wide QRS-Complexes
Authors: Vallentin Mikael F , Granfeldt Asger , Povlsen Amalie , Andersen Lars W
Published: June 2023

Introduction:
The Calcium for Out-of-hospital Cardiac Arrest (COCA)-trial recently found no benefit of administering calcium during out-of-hospital cardiac arrest in an unselected adult population. Still, calcium is recommended for cardiac arrest caused by hyperkalemia. Higher potassium levels have been found in cardiac arrest patients with wide QRS-complexes which may act as an indicator of hyperkalemia.

Objectives:
1) To describe characteristics of patients with baseline PEA in out-of-hospital cardiac arrest, and 2) to determine the effect of calcium on return of spontaneous circulation (ROSC) in patients displaying PEA with wide and normal QRS-complexes.

Methods:
COCA was a randomized, double-blind, placebo-controlled trial of calcium administered immediately after the first and second epinephrine dose of adults in out-of-hospital cardiac arrest. Of the 391 included patients, this abstract included those with PEA at the last rhythm analysis prior to first trial drug administration. PEA was defined as any rhythm that was not ventricular fibrillation, ventricular tachycardia, or asystole. Wide QRS-complexes were defined as > 110 ms.

Results:
104 patients had baseline PEA and available electrocardiograms. Demographics and electrocardiographic characteristics are presented in Table 1. The median heart rate was 42, half presented with an escape rhythm, and 70% had wide QRS-complexes. Half exhibited ST-elevation. The overall ROSC-rate was 31%. The relative risk of ROSC for patients receiving calcium as compared to placebo was 0.75 (95% confidence interval (CI) 0.33-1.72) in the normal QRS-group and 0.82 (95% CI 0.47-1.41) in the wide QRS-group.

Conclusion:
In adults with out-of-hospital cardiac arrest, baseline PEA rhythms often included bradycardia, escape rhythms, wide QRS-complexes, and/or ST-elevation. The effects of calcium administration on ROSC were similar in a subgroup analysis of normal vs. wide QRS-complexes.
Abstract 15210: Association of Circulating Biomarkers With Progressive Left Ventricular Remodeling and Hypertrophy in Patients With Aortic Stenosis: Results From the Progressa Study
Authors: Abdoun Kathia , Tastet Lionel , Shen Mylene , Capoulade Romain , Fleury Marie-Ange , Arsenault Marie , Bédard Elisabeth , Pibarot Philippe
Published: June 2023

Introduction:
Aortic stenosis (AS) is associated with progressive left ventricular (LV) remodeling and hypertrophy, ultimately leading to cardiac decompensation. Measurement of circulating biomarkers may be useful to identify AS patients with higher risk of maladaptive LV remodeling, a potent marker of the transition to heart failure. We hypothesized that multiple circulating biomarkers are associated with faster progression of LV hypertrophy in patients with AS.

Methods:
One hundred and forty-six asymptomatic AS patients (66±13years, 75% male) prospectively enrolled in the PROGRESSA study (NCT01679431) were included in this sub-analysis. All patients underwent Doppler-echocardiography to measure AS severity, LV mass indexed to body surface area (LVMi) and LV relative wall thickness (RWT). The annualized changes in LVMi and RWT were calculated between baseline and last follow-up visit (mean follow-up of 2.5±1.88 years).

Results:
At baseline, 16% of patients had mild (i.e. peak aortic jet velocity [Vpeak] 2.0-2.9 m/s),76% moderate (Vpeak 3.0-3.9 m/s), and 8% severe (Vpeak ≥4.0 m/s) AS, mean LVMi and RWT were 106±23 g/m
2
and 0.47±0.07 respectively. Among biomarkers, baseline level of triglycerides, D-dimer and tumor antigen 125(Ca-125) were significantly associated with LVMi progression rate (β:0.16,p≤0.05), (β:0.18,p≤0.05) and(β:-0.20,p≤0.05) respectively. Soluble (ST2) protein and alkaline phosphatase (ALP) were the only factors independently associated with the annualized change in RWT. In multivariate analysis adjusted for age, gender, comorbidities, AS severity, cardiac biomarkers; triglycerides and D-dimers remained significantly associated with faster progression rate of LVMi (all, p≤0.05), while lower level of CA125 remained significantly associated with LVMi annualized change (β=-0.21, p=0.01). After similar multivariate adjustment, higher levels of ST2 and ALP remained significantly associated with faster progression rate of RWT (all, p≤0.05).

Conclusion:
Several blood biomarkers were independently associated with faster progression of LV remodeling and hypertrophy in patients with AS. A multiple biomarker approach may be useful to assess LV health and predict the risk of early phases of heart failure in AS.
Abstract 15219: Optogenetic “Printing” of Reentrant Arrhythmias in Human Induced Pluripotent Stem Cell Derived Cardiac Tissues
Authors: Landesberg Michal , Wexler Yehuda , Arbel Gil , Huber Irit , Gepstein Lior
Published: June 2023

Introduction:
Current models used to investigate reentrant arrhythmias allow for limited control of arrhythmia parameters and morphology. Here, we developed a method for the induction of morphologically and physiologically defined arrhythmias using human induced pluripotent stem cell derived cardiac cell sheets (hiPSC-CCSs) and optogenetic tools.

Methods:
One million hiPSC-cardiomyocytes expressing the optogenetic channel CoChR were used to create the hiPSC-CCSs. Rotor illumination patterns were generated either by computer-aided design or by utilizing previously recorded rotor patterns. A digital micro mirror device (DMD) and a 470nm LED were used to project five complete cycles of these rotor patterns onto the hiPSC-CCSs.

Results:
Optical projection of typical rotors led to repeated development of arrhythmias in all sampled tissues (n=11). The resulting arrhythmias resembled the projected rotor patterns in terms of directionality (clockwise or counterclockwise) and number of cores ,and were highly reproducible for each projection (Fig.1A). Interestingly, we identified a minimal and maximal frequency of the projected rotor that could induce arrhythmias (Fig.1B). Moreover, the frequency of the generated rotor could not be increased beyond a certain value despite further increases in the projected rotor frequency (Fig.1B). Lastly, to assess the effects of tissue EP properties, the process was repeated after treatment with the IKr blocker E-4031 (30nM). E-4031 treatment significantly reduced the minimal and maximal frequencies of the projected rotor that could still induce arrhythmia and slowed the maximal frequency of the resulting rotor (Fig.1B).

Conclusions:
We present a new method for the optical induction of reentrant arrhythmias allowing the generation of rotors rapidly, reproducibly, and with a predesigned morphology. This approach may allow for a paradigm shift in the way reentrant arrhythmias are studied.
Abstract 15226: Association of Estimated Pulse Wave Velocity to Mortality in Heart Failure With Reduced Ejection Fraction. Insights From the HF-Action Trial
Authors: Mazimba Sula , Woodhouse Rebecca , Oyinloye Tolu P , Lamp Josephine , Ashur Nicholas , Shisler David , Taylor Lauren , Abuannadi Mohammad , Phillips Steven , Ibrahim Sami , Hossack John A , Mehta Nishaki M , Breathett Khadijah , Boadu Akua , Bergin James , Kwon Younghoon , Bilchick Kenneth C
Published: June 2023

Introduction:
Ventriculo-arterial coupling dynamics influence outcomes in heart failure (HF). Arterial stiffness (AS) is a key determinant of vascular load on the heart. We hypothesized that estimated pulse wave velocity (ePWV) would be associated with mortality.

Methods:
We analyzed the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) database for the association of ePWV with survival. ePWV was calculated using mean blood pressure (MBP) and Age using the equation: 9.587 – 0.402 х age + 4.560 х 10
–3
 х age

2

 – 2.621 х 10
–5
 х age
2
 х MBP + 3.176 х 10
–3
 х age х MBP – 1.832 х 10
–2
 х MBP. MBP was calculated as diastolic BP (DBP) + 0.4(SBP – DBP). Kaplan-Meier survival curves and Cox proportional hazards regression were used for analysis.

Results:
Among 768 patients (age 58.0 +/- 12.8 years, 31.8 % female), the median ePWV was 8.5 (IQR 7.2 to 10.2). There was a moderate correlation between ePWV and peak VO2 (r=-0.20, p<0.0001) and between ePWV and the six-minute walk duration (r=-0.20, p<0.0001). The unadjusted HR for ePWV and all-cause mortality was 1.15 per unit increase (95% CI 1.05-125). The unadjusted HRs for ePWV component covariates of age and MBP with all-cause mortality were 1.03 per year (95% CI 1.02-1.05, p < 0.0001) and 0.985 per mm Hg (95% CI 0.971-1.000, p=0.053), respectively. With adjustment by peak VO2 above or below the median in a multivariable model, increasing ePWV was still associated with a greater probability of all-cause mortality (HR 1.11 per unit increase, 95% CI 1.01-1.21, p=0.02). In the model with adjustment by the six-minute walk duration, risk associated with ePWV was similar (HR 1.09, 95% CI 0.998-1.120, p=0.056). Kaplan-Meier curves also demonstrated an increased risk for ePWV greater than the median value of 8.5 (Figure).

Conclusion:
ePWV is associated with all-cause mortality in stable HF patients. More studies are needed to assess the utility of ePWV as a therapeutic target in HF.
Abstract 15233: Risk of Venous Thromboembolism and Nonrheumatic Valvular Heart Disease in Patients With Elevated Lipoprotein(a): A Retrospective Cohort Study
Authors: Bloch Evan S , Elhanan Gai , Metcalf William J , Grzymski Joseph
Published: June 2023

Introduction:
Higher Lipoprotein(a) (Lp(a)) levels are known to be associated with increased risk of ASCVD. However, the effect of elevated Lp(a) on other cardiovascular (CV) diseases is largely unknown. We sought to identify whether Lp(a) level might be a risk factor for non-atherosclerotic CV conditions.

Methods:
Using data from the Healthy Nevada Project (HNP), a population genetic study based in Northern Nevada with >52,000 participants, we conducted a retrospective analysis of all participants with recorded Lp(a) levels. An exploratory analysis was performed examining associations between elevated Lp(a) levels and various CV conditions based on ICD 10 codes. Elevated Lp(a) was defined as >50 mg/dl or >125 nmol/L. We examined ICD 10 codes related to venous thromboembolic (VTE) disease and non-rheumatic valvular heart disease (VHD). A Fisher’s Exact Test was performed to assess the significance of these associations.

Results:
Out of 4,010 HNP participants (age: 62±30; 42.7% female) with an Lp(a) result, 881 had elevated Lp(a), with incidence ~7% higher (~30% vs. ~23%) in Black, Pacific, and Native American groups. Of those with elevated Lp(a) levels, 96 (10.9%) had diagnoses (dxs) of VTE vs. 270 of 3129 (8.6%) participants with normal Lp(a) (p=0.046). Specifically, 9.76% of elevated Lp(a) participants vs. 7.51% of normal Lp(a) participants had dxs of DVT (p=0.035). No significant difference was found between elevated Lp(a) and PE. Additionally, 227 (25.8%) participants with elevated Lp(a) had VHD dxs compared to 593 (18.9%) participants from the normal Lp(a) cohort (p=0.0001). Specifically, 14.98% of elevated Lp(a) participants vs. 10.48% of normal Lp(a) participants had Aortic VHD (p=0.0003), and 14.87% of elevated Lp(a) participants vs. 10.35% normal Lp(a) participants had Mitral VHD (p=0.0003). No significant association was found between elevated Lp(a) and pulmonic or tricuspid VHD. Less novel but significant associations between elevated Lp(a) and Stroke (p=0.046) and CAD (p=0.0001) were also observed.

Conclusions:
In our study, elevated Lp(a) levels were significantly associated with increased risk of VTE and nonrheumatic VHD. An examination of these risks in association with germline genetic studies of ASCVD in the HNP is ongoing.
Abstract 15254:
Acta2
Missense Variant Increases Atherosclerotic Plaque Burdern by Heat Shock Factor 1-Driven Augmented Phenotypic Modulation of Smooth Muscle Cells
Authors: Kaw Kaveeta , Chattopadhyay Abhijnan , Guan Pujun , Chen Jiyuan , Majumder Suravi , Duan Xue Yan , Ma Shuangtao , Zhang Chen , Kwartler Callie , Milewicz Dianna M
Published: June 2023

ACTA2
encodes the contractile protein smooth muscle α-actin expressed in smooth muscle cells (SMCs). A heterozygous pathogenic variant in
ACTA2
, p.R149C, predisposes to premature coronary artery disease (CAD) in the absence of risk factors. Recent studies have determined that SMCs contribute to atherosclerotic plaque formation after undergoing phenotypic modulation, characterized by de-differentiation and increased expression of macrophage, fibroblast, stem, and osteogenic markers. This SMC modulation is driven in part by exogenous cholesterol entering the endoplasmic reticulum (ER) and activating ER stress, specifically PERK signaling. To determine how a mutation in SM α-actin predisposes to atherosclerosis,

Acta2
R149C/+

mice were crossed into
Apoe
-/-
mice and fed a high fat diet for 3 months. Despite no differences in serum lipid levels, the

Acta2
R149C/+
Apoe

-/-
mice have a 3-fold increased plaque burden compared to
Apoe
-/- mice. SMCs explanted from

Acta2
R149C/+

mice have phenotypic modulation at baseline while WT SMCs do not. We determined that misfolding of the R149C SMα-actin activates heat shock factor 1 (HSF1), which increases endogenous cholesterol biosynthesis through increasing HMG-CoA reductase expression. The increase in endogenous cholesterol levels induces ER stress, activates PERK, and augments both modulation of SMCs and atherosclerotic plaque formation. ScRNA sequencing confirms increased HSF1 and PERK signaling and modulation in SMCs in the mutant mice. Importantly, pravastatin treatment dramatically lowers plaque burden to similar low levels of plaque burden in both the

Acta2
R149C/+
Apoe

-/- and
Apoe
-/-
mice
(Fig. 1a)
. These studies identify a novel mechanism by which mutant SM α-actin increases endogenous cholesterol biosynthesis and drives atherosclerotic plaque formation, a mechanism that also informs as to why statins are effective in individuals at risk for CAD who do not have elevated plasma cholesterol levels
(Fig. 1b)
.
Abstract 15267: LV Aneurysm Rupture - Dreaded Complication in an LVAD Patient
Authors: Chima Noor , Luibil Nicholas , Azizi Abdul H , Gakhal Mandip S , Fabrizio Carly
Published: June 2023

Introduction:
Left ventricular (LV) aneurysm rupture is a highly fatal mechanical complication, usually seen following a myocardial infarction. We describe a unique case of a patient with a left ventricular assist device (LVAD) who presented with cardiac arrest due to an LV aneurysm rupture.

Case:
A 57-year-old male with history of ischemic cardiomyopathy status post HeartMate3 (HM3) LVAD presented as an out of hospital cardiac arrest. Following resuscitation, Computed Tomography Angiography (CTA) of the chest showed a large long-standing aneurysm along the inferior wall of the LV measuring 2.9 x 3.3 x 3.5 cm with rupture dissecting the pericardium and extending to cause hemo-peritoneum (Figure1), not amenable to intervention. He had presented earlier in the month with anemia that stabilized with transfusion. Abdominal imaging at the time showed a contained bleed with unknown source. He had likely suffered a progressive bleed from the rupture leading to his cardiac arrest.

Decision Making:
Pseudoaneurysm has been reported as a rare complication with earlier generation LVADs, but to our knowledge, this is the first reported case of an aneurysm formation with rupture with an HM3 LVAD.

Conclusions:
With the advent of advanced mechanical support devices, there is a heightened need for awareness and cognizance of diagnosing such mechanical complications in this patient population. An early diagnosis requires a high clinical index of suspicion and a multi-disciplinary approach. Multimodality imaging including CT scan can assist with this diagnosis.
Abstract 15282: COVID-19 Cases, Hospitalizations, and Vaccination Among Adults With Congenital Heart Disease
Authors: Oster Matthew , Velani Romie N , Claxton J'Neka S , Kuo Kristina W , Aldoss Osamah , Canter Charles E , Gaitonde Mansi , John Anitha , Malikarjun gurumurthy H , McHugh Kimberly , Overman David M , Raghuveer Geetha , Spector Logan , Kochilas Lazaros
Published: June 2023

Background:
There are conflicting data as to whether congenital heart disease (CHD) should be considered a condition that places a person at high risk of severe illness from COVID-19. The objective of our study was to compare COVID-19 cases, hospitalization rate, and vaccine uptake among adults with history of cardiac intervention vs. the general US adult population.

Methods:
We performed a cross-sectional study of adults using survey data from the Congenital Heart Disease Project to Understand Lifelong Survivor Experience (CHD PULSE). This survey, conducted in 2021-2022, queried CHD survivors regarding a variety of domains, including history of COVID-19 infection and vaccination. Adults with a history of surgical, catheter, or electrophysiologic intervention at 1 of 8 Pediatric Cardiac Care Consortium centers were eligible for inclusion. Results were limited to those aged 18-49 years to allow comparison to age-specific data from the US Centers for Disease Control and Prevention.

Results:
Among 1,277 respondents (20.2% response rate), the median age was 32 years (IQR: 27-38 years), the majority were female (55.6%), and the most common race/ethnicity was Non-Hispanic White (89.9%). There was no difference in history of a positive COVID-19 test in persons with CHD compared to adults of a similar age (26.8% vs 28.1%, p=0.86). However. those with CHD and COVID-19 were significantly more likely to require hospitalization than adults in the general population with COVID-19 (1.75% vs. 0.26%, p=0.004) (Figure). Regarding COVID-19 vaccination, 76.5% of CHD PULSE respondents reported a history of at least 1 COVID-19 vaccine, with no differences vs. the general population when compared by age (p=0.99).

Conclusions:
Given higher hospitalization rates among adults with CHD and COVID-19, CHD should be considered a medical condition that places one at increased risk of severe COVID-19. These findings underscore the importance of COVID-19 vaccination in this population.
Abstract 15290: Hypertension in Black and White Breast Cancer Survivors: NCT02992730
Authors: Sheppard Vanessa B , Sutton Arnethea L , Lucas Alexander R , Franco Robert L , Reding Kerryn , Kim Youngdeok , Cheng Richard , Wells Matthew B , Hundley William G
Published: June 2023

Introduction:
Hypertension (HTN) may increase the risk of cardiovascular (CV) events among breast cancer (BC) survivors, particularly in Black women. Limited information is available about factors associated with the presence of HTN at the time of BC diagnosis among Black versus White women.

Methods:
In a secondary analysis of data from a longitudinal cohort of Black and White women diagnosed with hormone receptor positive (HR+) BC, post initiation of adjuvant endocrine therapy (AET), medical records were used to determine HTN status and other clinical factors (stage, AET type, CV comorbidities). In the same cohort, psychosocial and quality of life data were collected via surveys. Logistic regression models evaluated factors associated with increased odds of HTN at baseline.

Results:
Women with BC (n=243) were mostly White (66.7%), mean (SD) aged 61.6 (10.9) years, with borderline obesity (BMI: 29.9 (6.6)). Comorbidities and tamoxifen use were reported by 40.7% and 28.4% of women, respectively. HTN was present in 140 (57.6%) women (38% Black, 62% White). Relative to their White counterparts, Black women with HTN were significantly younger, (61.5 vs. 67.5 years of age,
p<
0.01) more overweight (BMI, 32.8 vs 29.3,
p
=<.01), received chemotherapy more frequently (44.4% vs 22.1%,
p
<0.01), were more likely to have experienced discrimination (35.2% vs 7%,
p
<0.01) and more often to possess CV comorbidities (61.1% vs 37.2%,
p
<0.01). Multivariable logistic regression showed that the odds of having HTN increased significantly with age by 10% per year (OR: 1.10, 95% CI: 1.06-1.14; p<.0001), with Black women having a 2-fold greater risk of having HTN (OR: 2.02, 1.02-4.03; p=.044) than White women. Additionally, a 1-unit increase in BMI was associated with 6% higher odds of having HTN (OR: 1.06, 95% CI: 1.03-1.11; p=0.0390) while Tamoxifen use, presence of CV comorbidities and worse social well-being were not associated with more frequent HTN in women with BC.

Conclusions:
A high proportion of women diagnosed with HR+ BC have HTN with Black vs White women experiencing more HTN. These results raise the possibility that Black women with BC may benefit from focused HTN management strategies to reduce potential CV events.
Abstract 15300: Tirzepatide vs. Semaglutide for Weight Loss in Patients With Type 2 Diabetes Mellitus - A Value for Money Analysis
Authors: Azuri Joseph , Hammerman Ariel , Aboalhasan Enis , Sluckis Ben , Arbel Ronen
Published: June 2023

Introduction:
Higher doses of the glucagon-like peptide-1 agonist (GLP-1RA) semaglutide and, more recently, the GIP and GLP-1RA tirzepatide demonstrated a significant reduction in body weight in patients with Type 2 Diabetes Mellitus (T2DM). However, their comparative value for money for this indication is unclear.

Hypothesis:
Tirzepatide provides better value for money than semaglutide in facilitating weight loss.

Methods:
We calculated the cost needed to treat (CNT) to achieve a one percent reduction in body weight using high-dose tirzepatide (15mg) versus semaglutide (2.4mg). The body weight reductions were extracted from published results of SURMOUNT-1 and STEP 1 trials, respectively. We performed a scenario analysis to mitigate the primary differences between the two studies' populations (Table 1). Drug costs were based on US GoodRx prices as of June 2022.

Results:
Using tirzepatide resulted in weight loss of 17.8% (95% CI: 16.3%-19.3%) compared to 12.4% (95% CI: 11.5%-13.4%) for semaglutide. The total annual cost of therapy with tirzepatide was estimated at $17,554 compared with $22,899 for semaglutide. Accordingly, the CNT per one percent of body weight reduction with tirzepatide is estimated at $987 (95% CI:$910-$1,077) compared to $1,847 (95% CI: $1,708-$1,991) with semaglutide. Scenario analysis confirmed these findings.

Conclusions:
Tirzepatide provides better value for money than semaglutide for weight reduction at high doses.
Abstract 15305: The Dynamic Behavior of Polymer Microbubbles During Long Ultrasound Tone-Burst Excitation and Its Application for Sonoreperfusion Therapy
Authors: Chen Xucai , Chen Xianghui , Wang jianjun , Yu Francois T.H. , Villanueva Flordeliza S , Pacella John
Published: June 2023

Objective:
Ultrasound (US)-targeted microbubble (MB) cavitation (UTMC) mediated therapies have been shown to restore perfusion and enhance drug/gene delivery. Due to the potentially longer circulation time and relative ease of storage and reconstitution of polymer shelled MBs compared with lipid MBs, we investigated the dynamic behavior of polymer MBs and its therapeutic potential for sonoreperfusion (SRP) therapy.

Methods:
We explored the fate of polymer MBs during a single long tone-burst exposure (1 MHz, 5 ms) at various acoustic pressures (0.25-1.5 MPa) and MB concentrations (2х10
6
-2х10
8
MB/mL) via direct high-speed microscopy observation and passive cavitation detection (PCD) and compared with lipid MBs. SRP efficacy of these MBs was investigated in an
in vitro
constant flow system at various pulse durations (1 MHz, 1-5 ms every 3 sec for 20 min) and acoustic pressures (0.6-1.5 MPa). The pressure differential across a porous mesh partially occluded with microthrombi was recorded as a function of time during treatment and used as a measure of thrombus burden. The terminal pressure drop and the initial rate of pressure drop were derived and compared.

Results:
Both polymer and lipid MBs first underwent stable or inertial cavitation depending on the acoustic pressure, and then formed gas-filled clusters that continued to oscillate, fragment, and form new gas-filled clusters during the single US burst. PCD confirmed continued acoustic activity throughout the 5-ms US excitation. SRP efficacy with polymer MBs increased with the pulse duration and acoustic pressure (
p
<0.05, ANOVA), similarly to that of lipid MBs, but no significant differences were found between polymer and lipid MBs (
Figure 1
).

Conclusion:
Under the acoustic conditions tested, both polymer and lipid MBs demonstrate similar thrombolytic effects
in vitro
suggesting that persistent cavitation activity from polymer MBs during long tone-burst US confers excellent reperfusion efficacy.
Abstract 15313: Hypoglycemia: The Forgotten "H&T" in Cardiac Arrest
Authors: Lau Hui Chong , Ng Sze Jia , Saeed Subha , Tahir Muhammad Moiz , Hlaing Swe Swe , Rai Navjot , Gaiba Rahul
Published: June 2023

Introduction:
Hypoglycemia is known to cause cardiac arrhythmias and even sudden cardiac death by inducing oxidative stress, QT prolongation, and myocardial injury. Chromosomal deletion of 1p36 is associated with learning difficulty, progressive renal disease, and cardiomyopathy. To our knowledge, this is the first case of a patient with 1p36 deletion syndrome and end-stage renal disease (ESRD) who developed cardiac arrest due to hypoglycemia.

Case Presentation:
A 26-year-old female presented to the emergency department with generalized itching, weakness, and progressive dyspnea after missing multiple hemodialysis (HD) sessions. She was admitted for HD and her stay was complicated by an episode of coffee-ground emesis and she was nil per oral (NPO) for an endoscopy. That night, the patient became bradycardic and had a cardiac arrest with pulseless electrical activity (PEA). Fingerstick blood glucose was undetectable during resuscitation and ROSC was achieved instantaneously after dextrose administration. The patient had no history of diabetes and was refusing glucose checks while NPO. She had a remarkable neurological recovery post-cardiac arrest. However, her glucose levels remained persistently low despite maximally tolerated feeds. An extensive workup for persistent hypoglycemia including peptide C levels, hba1c, and insulin level were within normal limits. Her cortisol level was appropriately raised. CT scan of the head performed was normal. Cardiac catheterization revealed no coronary artery disease.

Discussions:
Hypoglycemia was removed from the Advanced Cardiovascular Life Support (ACLS) algorithm as a reversible cause of cardiac arrest in 2010. Our case is a reminder of a life-threatening yet quickly reversible cause of cardiac arrest.

Conclusions:
ESRD increases the risk of hypoglycemia due to decreased insulin clearance and must be carefully monitored while NPO. Physicians have to be aware that routine dextrose administration during cardiac resuscitation does not improve survival and neurological outcomes.
Abstract 15314: Advanced Cardiovascular Imaging for the Diagnosis of Mycobacterium Chimaera Prosthetic Valve Infective Endocarditis After Open-Heart Surgery: A Systematic Review
Authors: Sanchez-Nadales Alejandro , Diaz Sierra Alejandra V , Xu Bo
Published: June 2023

Introduction:
Mycobacterium chimaera is an emerging pathogen, recognized to cause prosthetic valve infective endocarditis (PVIE) and disseminated infection following open-chest cardiac surgery with certain contaminated heater-cooler systems. Diagnosis is challenging and requires a very high index of suspicion. Data regarding the optimal cardiac imaging evaluation of this condition is limited.

Methods:
Scopus, PubMed, EMBASE, Ovid and Cochrane were searched for published articles through October 2021, using keywords “Mycobacterium chimaera”, “Prosthetic valve” and “Endocarditis”. 169 articles were found and reviewed for study eligibility. Articles were included if they consisted of Mycobacterium chimaera causing IE, with imaging modalities used to establish diagnosis

Results:
Thirty-three articles were included, yielding twenty-two cases of Mycobacterium chimaera PVIE. The disease manifested on average thirty months after surgery, with an average patient age of 59 years (90% male). Imaging modalities to establish the diagnosis of prosthetic valve infective endocarditis included: transthoracic echocardiogram in 5 cases, transesophageal echocardiogram (TEE) in nine cases, 18F-FDG-PET/CT in seven cases. A combination of imaging modalities with TEE and 18F-FDG-PET/CT was reported once; TTE, TEE and 18F-FDG-PET/CT was also noted in one case. Lastly there was one instance each of combined use of TTE, TEE, and one of the following: CTA, Cardiac MRI, or standard CT. Nine cases did not specify the imaging modality used to achieve diagnosis. Ten patients died.

Conclusions:
PVIE due to Mycobacterium chimaera infection is a rare and challenging diagnosis, which requires a high index of suspicion. Accurate diagnosis should be aided by multimodality cardiac imaging, with 18F-FDG-PET/CT being a powerful adjunct imaging modality.
Abstract 15317: An Unusual Case of Recurrent Chest Pain: Lymphocytic Myocarditis
Authors: Majid Muhammad , Yaker Zachary S , Dugan Eunice S , Tan Carmela D , Cremer Paul C , Klein Allan L
Published: June 2023

Case Presentation:
A 42-year-old male with a past medical history of recurrent myopericarditis treated with a combination of NSAIDs, colchicine, and steroids presented for left-sided chest pain. The pain first recurred when he attempted a prednisone taper and he was started on Anakinra. Upon presentation, physical examination and laboratory findings were within normal limits. Echocardiography and electrocardiogram were within normal limits. Cardiac magnetic resonance imaging (CMR) showed transmural enhancement of the basal-mid inferolateral segments and patchy mid-myocardial enhancement in the basal-mid anterolateral segments. Nuclear medicine PET showed FDG uptake in the basal anteroseptal, anterolateral, inferolateral, inferior, and apical segments suggestive of active inflammation. Initially, the diagnosis was thought to be recurrent myopericarditis of unknown etiology. Subsequent right heart catheterization with endomyocardial biopsy (EMB) showed mononuclear infiltrates in the interstitium associated with myocyte infiltration and focal moderate interstitial fibrosis. Due to his clinical, imaging, and pathologic findings, he was diagnosed with lymphocytic myocarditis. His anti-inflammatory therapy regimen was reinstated, and he was started on Mycophenolate Mofetil. On follow-up, the patient had significant symptomatic improvement.

Discussion:
Lymphocytic myocarditis is a pattern of myocardial inflammation that is typically associated with autoimmune and idiopathic causes. Myocarditis frequently manifests with signs and symptoms of heart failure, including chest pain, dyspnea, and arrhythmias. Diagnosis of myocarditis is often supported by CMR and FDG-PET findings, however, EMB is the gold standard for the diagnosis of myocarditis. Treatment is generally supportive, though immunomodulatory therapies have gained increased popularity due to benefits in treating symptoms and preventing complications of heart failure.
Abstract 15318: Global Deletion of P90 Ribosomal S6 Kinase Provides Cardiovascular Protection Against Age-Related Hypertension
Authors: Ayon Ramon J , Wang Yves T , Kalra Jaspreet , Markowska Zaneta , Sonkusare Swapnil K , Le Thu H , Somlyo Avril V
Published: June 2023

Background:
Hypertension (HT) is highly prevalent and associated with significant mortality and morbidity among older individuals. Aging is associated with structural and functional remodeling of the vasculature, similar to blood vessel alterations observed in HT. We previously demonstrated that young adult global
Rsk2
KO mice had more dilated mesenteric arteries (MAs), with reduced vessel tone, stiffness and RLC
20
phosphorylation, and significantly lower basal blood pressure compared to WT. However, it is unknown whether RSK2 plays a role in age-related HT.

Hypothesis:
Loss of RSK2 signaling in aged mice inhibits age-related- and L-NAME-induced HT, arterial stiffness, and vascular remodeling.

Methods:
Systolic blood pressure (SBP) measurements of >24-month-old global
Rsk2
KO and WT males were performed daily for 2 weeks after 2 weeks of daily training using tail cuff manometry. Baseline echocardiographic (echo) parameters were measured. N(G)-Nitro-L-arginine-methyl ester (L-NAME) was administered (20 mg/kg/day) via drinking water to induce HT. Pressure myography studies assessed vascular reactivity and arterial stiffness in MAs isolated from
Rsk2
KO and WT mice. Aorta and MAs were sectioned and stained to examine structural changes.

Results:
WT mice had a significantly higher mortality rate (63.6%) compared to
Rsk2
KO (12.5%). Baseline SBP was also significantly higher in WT compared to KOs (123±10 vs. 99±12 mmHg, p < 0.001, n = 9/7). L-NAME elevated SBP in WT but not in KO mice (137±2 vs. 97±8 mmHg, p < 0.00001, n = 4/7). Although there were no differences in echo parameters, we observed a negative correlation between ejection fraction (EF) and SBP in WT (-0.94 %/mmHg, p = 0.046, R
2
= 0.59, n = 6), but not in
Rsk2
KO mice (p = 0.15, n = 7). Functional and histological studies in aged KO mice are ongoing to examine age-related changes in vascular reactivity and remodeling.

Conclusion:
Loss of RSK2 reduces BP levels in aged mice akin to young adult mice. Additionally, the hypertensive effects of L-NAME are absent in aged
Rsk2
KO mice. Aged
Rsk2
KO mice appear to be protected from cardiovascular effects associated with age-related HT. Therapeutic targeting of RSK2 could prove beneficial for reducing risk of cardiovascular diseases associated with HT in the elderly.
Abstract 15319: Left Ventricular Assistant Device (lvad) Support Did Not Alter Mirna Expression in Heart Failure Patients
Authors: Dhar Kajari , Basma Hesham , Um John , Qiu Fang , Lowes Brian D
Published: June 2023

Introduction:
Micro RNAs (miRNA) are crucial regulators of various biological processes including the pathogenesis of heart failure (HF). In this study, miRNA profiling was compared with pre and post LVAD and non-failing (NF) control heart patients. Our goal was to identify miRNAs involved in HF and responses to LVAD therapy.

Methods:
Myocardial RNAs were isolated from non-ischemic dilated cardiomyopathy patients (n=22) who went through LVAD placement (pre LVAD) and later transplant (post LVAD) along with 6 normal hearts as controls. NanoString technology was used to quantify miRNA expressions. NanoString miRNAs raw count data were preprocessed and normalized using solver 4.0 Analysis Software. Ingenuity Pathway Analysis (IPA) was done by differentially expressed miRNA to understand the biological pathways involved.

Results:
Our sample population exhibited 80% male and 95% Caucasian with an average age of 57 and ejection fraction was less than 25% at the time of LVAD placement. The average LVAD duration of patients was 525 days. One ninety-five miRNAs in pre and 120 miRNAs in post LVAD patients were differentially expressed compared to control using cutoff of for the FDR adjusted p-value 0.05 and at least 2-fold changes. There was no significant change in miRNA expression when post LVAD was compared with pre LVAD patients. IPA analysis revealed that there are 15 up-regulated miRNA that promote apoptosis with a net Z score of 2.155 in post LVAD versus control. There are 27 miRNAs with a net of apoptotic with a Z score 0f 0.766 in pre LVAD versus control. It was also noticed from IPA analysis that expression of 8 identical miRNAs in both pre and post LVAD patients were involved in heart fibrosis. LVAD therapy did not change the miRNA expression

Conclusions:
Our results identify many miRNAs that are associated with apoptosis and fibrosis in end stage heart failure. Molecular mechanisms of heart disease will be identified by miRNA profiling and function as potential biomarkers or therapeutic targets in future. LVAD therapy does not substantially reverse these epigenetic changes in this population.
Abstract 15324: The Fontan Circulation Shows Decreased Cell Survival and Oxidative Damage
Authors: Tripathi Dipti , Lecointe Joiliana A , Zhu Aihua , Ichimura Shoko , Clouthier Katie , Reddy Sushma
Published: June 2023

Introduction:
Single ventricle congenital heart disease such as hypoplastic left heart syndrome (HLHS) with a Fontan circulation accounts for the largest group of children hospitalized with circulation failure, with an in-hospital mortality of 20-50%. We sought to (i) evaluate the mechanisms underlying circulation failure and (ii) identify novel therapeutic targets.

Methods:
Blood was collected from patients with HLHS s/p Fontan and from controls with normal cardiac anatomy and function (N=5/group). Plasma microvesicles (MV) were isolated and proteomics assessed using data independent acquisition mass spectroscopy. Dysregulated proteins with a fold change >1.5 or < -1.5, p<0.05 were evaluated using Ingenuity pathway analysis.

Results:
Age of Fontan patients vs. controls was 17.04±2 vs. 15.7±2.5, p=0.4; 20% were male in both groups. 60% of Fontan patients were in NYHA class II/III, 40% in NYHA class IV; 80% had Fontan-associated liver disease. Circulating MVs were released from cardiomyocytes, endothelial cells, and hepatocytes based on cell surface markers. Upregulated proteins (N=27) implicated cell death pathways (Solute carrier family 2, Angiotensinogen, CD14); while downregulated proteins (N=88) implicated impaired cell survival (tyrosine-protein kinase Yes, endothelial growth factors). MVs contained mitochondria and endoplasmic reticulum proteins implicating upregulation in reactive oxygen species signaling (catalase A, S100A8) and downregulation in antioxidant enzymes (GPX1, PRDX 5).

Conclusion:
Circulating MVs from patients with HLHS s/p Fontan are released from the heart, blood vessels, and liver providing a noninvasive signature of organ remodeling. The MV protein cargo implicates heightened cell death, oxidative damage and impaired cell survival, thereby providing insight into the mechanisms of Fontan associated circulation failure.

Figure: Decreased Cell Survival and Oxidative Damage in the Fontan Circulation
Abstract 15330: Association of Cognition With Self-Care and With Health-Related Quality of Life in Heart Failure: Does Gender Moderate the Associations?
Authors: Jung Miyeon , Apostolova Liana G , Gao Sujuan , Moser Debra K , Gradus-Pizlo Irmina , Algashgari Elham , Wang Suzanne , Smith Asa B , Pressler Susan J
Published: June 2023

Introduction:
The associations of cognition with self-care of heart failure (HF) or with health-related quality of life (HRQL) have not been definitively established, Gender may moderate these associations. The aim of our study was to examine the associations between cognition and (1) HF self-care and (2) HRQL and explore (3) gender as a moderator.

Methods:
Baseline data were analyzed from a randomized trial of a cognitive intervention (N=73). A neuropsychological battery was used to assess cognition (i.e., global cognition, memory, attention, executive function, language). Self-Care of Heart Failure Index and Minnesota Living with Heart Failure were used to assess self-care (i.e., maintenance, management, perception, confidence) and HRQL, respectively. Moderated multiple regressions were performed using Hayes’ PROCESS macro v4.1 with cognition as the independent variable, gender as the moderator, and HF self-care or HRQL as dependent variables in separate models. Covariates were age and education.

Results:
Participants’ characteristics were: mean age=66±12 years; mean education=14±2 years; 56% women; mean LVEF=50±14%. Average scores were: self-care maintenance=68±12, management=64±16, perception=74±16, confidence=78±13, HRQL=29±22. Better attention scores were significantly associated with better self-care confidence (b=-1.002, p=.022). Gender moderated the relationships between attention and self-care perception (p=.030). Better attention was associated with better self-care perception among women but with worse self-care perception among men. Gender moderated the relationships between memory and HRQL (p=.050) as well as executive function and HRQL (p=.041). Women’s HRQL did not differ by memory or executive function, but men with better memory or executive function had better HRQL.

Conclusion:
Better attention was associated with better self-care confidence in HF. Associations between attention and self-care perception, memory and HRQL, and executive function and HRQL differed by gender. Interventions are needed to improve attention, memory, and executive function that may improve HF self-care and HRQL. The effects of gender need to be considered when designing future interventions.
Abstract 15349: Factors Associated With Progression of Latent Rheumatic Heart Disease
Authors: Beaton Andrea Z , Okello Emmy , Rwebembera Joselyn , Engelman Daniel , Carapetis Jonathan , DEWYER ALYSSA , Fall Ndate , Lwabi Peter , Mirabel Mariana , Mocumbi Ana O , nakitto miriam , Ndagire Emma , Nunes Maria D , Pulle Jafesi , Omara Isaac , Sarnacki Rachel , Scheel Amy , Wilson Nigel , Zimmerman Meghan , Zuhlke Liesl , Karthikeyan Ganesan , Sable Craig A , Grobler Anneke , Steer Andrew
Published: June 2023

Introduction:
Secondary antibiotic prophylaxis improves outcomes for children diagnosed with latent rheumatic heart disease (RHD). However, many children with latent RHD show improvement without prescription of prophylaxis. The objective of this study was to determine if specific sociodemographic or echocardiographic features are associated with progression of latent RHD.

Methods:
This is a retrospective analysis of the GOAL Trial, a randomized controlled trial of secondary antibiotic prophylaxis in children with latent RHD conducted in Uganda. Sociodemographic and echocardiographic variables were collected at trial entry. Progression was defined by a change in echocardiographic category according to the World Heart Federation Criteria (WHF; normal, borderline RHD, mild definite RHD, moderate/severe RHD), determined by consensus of a blinded 4-member adjudication panel. The association of risk factors with progression were calculated as odds ratios (OR) with 95% confidence intervals (CI) using logistic regression models adjusted for the randomized treatment arm and the stratification variable (definite/borderline RHD).

Results:
Outcomes for the 799 children who completed the GOAL Trial were included in this analysis. Female sex (OR 2.6, 95% CI 1.19-5.68, p=0.016) and poorer socioeconomic conditions (WAMI Index 0-1 with 1 being the least deprived, OR 0.48 for every 0.10-point increase) were associated with progression. There was no difference in risk of progression or regression between those with borderline RHD or mild definite RHD.

Conclusions:
Females and those living in less advantaged conditions were more likely to show progression of latent RHD. The strength of these associations was relatively low and does not warrant restricting prophylaxis to subgroups based on risk factors. The lack of difference in progression risk between those with borderline and those with definite RHD may impact revisions of the World Heart Federation Criteria for latent RHD diagnosis and calls into question the use of the term ‘borderline RHD’.
Abstract 15359: Multi-Omics Integration Reveals Mechanosensitive Regulatory Pathways in Cardiac Fibroblasts
Authors: Morningstar Jordan E , Beck Tyler , Gensemer Cortney , Biggs Rachel , Petrucci Taylor , Guo Lilong , Vohra Ayesha , Mai Le , Gonzalez Melfry , Stoddard Andrew , Dunne Jaclyn , Norris Russell A
Published: June 2023

Introduction:
Regionalized myocardial fibrosis exists in the inferobasal myocardium of patients undergoing surgical repair for Mitral Valve Prolapse, and supports a process in which cells within mechanically stressed myocardial regions alter their phenotype in order to increase tissue stiffness, eventually causing establishment of a fibrotic scar. How cells behave in different fibromechanical environments is not currently well understood.

Hypothesis:
Integrating RNA Seq and ATAC Seq datasets will identify mechanosensitive regulatory pathways in cardiac fibroblasts.

Methods:
Primary human cardiac fibroblasts (HCFs) were cultured on stiff (TC Plastic, ~2GPa), as well as soft (2kPa) substrates coated with type 1 collagen. Following 48 hours in serum-free conditions, HCFs were lysed and subjected to immunofluorescence (IF), Western blotting (WB), RNA Seq, and ATAC Seq. Differential analysis of RNA Seq, and ATAC Seq data was performed, followed by an integration analysis which linked differentially expressed genes to chromatin that opened/closed within 10 kB. Finally, motif enrichment analysis was performed using the online bioinformatics package Homer.

Results:
IF and WB revealed that HCFs cultured on a stiff substrate expressed markers of fibroblast activation (alpha SMA, P<0.0001), as well as increased amounts of Connexin 43 (P<0.0001). Additionally, there were higher numbers of Ki-67 positive cells (7.2% vs 2.1% P=0.001). RNA Seq revealed differential changes in 4324 genes (FDR adjusted P<0.05), several of which were subsequently validated using western blots. ATAC Seq identified 5855 chromatin regions which opened/closed in response to different mechanical environments in fibroblasts (adjusted P<0.05). Integrating RNA Seq and ATAC Seq datasets revealed 803 Chromatin changes that fell within 10kb of differentially expressed genes, with a predicted enrichment of TEAD binding sites in differentially opened chromatin (P=1.0*10-40).

Conclusions:
The mechanical environment plays a major role in cellular phenotype and directly regulates chromatin organization and expression of pro-fibrotic genes, with a possible role for TEAD as a driver of fibroblast activation.
Abstract 15363: Safety of Leadless Pacemakers vs. Transvenous Pacemakers in Patients Older Than 65 Years
Authors: Romero Jorge , Rodriguez Daniel , Diaz Juan C , Alviz Isabella , Haroun Magued , Nino Cesar , Duque Mauricio , Bastidas Oriana , Gamero Maria , Cerna Luis , Gabr Mohamed , Velasco Alejandro , Matias Jose , DAVE KARTIKEYA P , Della Rocca Domenico G , Mohanty Sanghamitra , Natale Andrea , Di Biase Luigi
Published: June 2023

Introduction:
Leadless pacemakers (LP) are a less invasive option compared to conventional transvenous pacemakers (TVP). They were introduced with the hope of eliminating complications associated with TVP and leads, which are more common among the elderly population. However, evidence supporting their use is uncertain. This study aims to compare the safety of the LP compared to TVP in patients 65 and older.

Methods:
We retrospectively analyzed consecutive patients, aged 65 and older, who were implanted a LP or TVP between August 2017 and November 2021, in 2 experienced Cardiovascular centers. The primary endpoint was a composite of any procedure-related complication (hematoma, venous thrombosis, infections, hemothorax, device dislodgement, pneumothorax). The secondary endpoint was the need for reinterventions.

Results:
A total of 313 patients were included; 219 received a TVP and 94 patients received a LP. Of the TVPs implanted, 68% used cephalic access, 21% axillary and 11% subclavian. The mean age was 78.9 + 7.76 for the TVP group and 82.6 +8.83 for the LP group. A total of 23 patients in the TVP group reached the primary end point vs 4 patients in the LP group, with a relative risk reduction of 60% of procedure related complications in LP compared to TVP (risk ratio [RR]:0.4; 95% CI (0.144-1.139); P= 0.043). In addition, 8 patients in the TVP group reached the secondary outcome vs none in the LP group (3.65% vs. 0%; p= <0.00001).. There were no statistically significant differences in individual outcomes between the TVP group and the LP group: incision-site hematomas (11 (5%) vs. 2 (2.1%); p=0.24), venous thrombosis (2 (2%) vs 1 (0.5 %); p=0.9), infections (1 (0.5%) vs 1 (1%) ; p=0.54), hemothorax (1 (0.5%) vs. 0 (0%); p=1), device dislodgement (8 (3.6%) vs 0 (0%); p=0.11), pneumothorax (none in either group).

Conclusion:
This study demonstrates that LP is a safer option than TVP among patients aged 65 and older. Additional studies are needed to further establish these findings.

1