bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14598: Relationship of Ambulatory Blood Pressure Profiles on Progression of Aortic Atheroma in Patients With Stroke
Authors: Shin Sung-Hee , Jang Ji Hun , Park Hee-Kwon
Published: June 2023

Introduction:
Aortic atherosclerotic burden is known to be associated with an increased risk of ischemic stroke. However, longitudinal data and the risk factors about aortic plaque progression are limited.

Hypothesis:
We hypothesized that ambulatory blood pressure (BP) variables would play a role in progression of aortic atheroma over 2 years in patients with stroke

Methods:
115 patients with who underwent serial transesophageal echocardiography (TEE) over 2 years were enrolled. Aortic atheroma was graded as mild (2-3mm), moderate (3-5 mm), severe (>5mm), or complex (ulceration and/or mobile component) using TEE. Progression of aortic atheroma was defined as an increase of maximal plaque thickness by ≥1 grade. Ambulatory BP monitoring (ABPM) was performed when BP was stabilized. The association between ABPM variables and aortic atheroma progression was assessed.

Results:
During the median follow-up of 25.0 months, 10 (8.7%) were regressed, 13 (11.3%) were progressed, and 92 (80.0%) remained unchanged. Female had more progression of aortic atheroma (p=0.007). However, baseline LDL cholesterol, change of LDL cholesterol, intensity of statin and baseline plaque thickness were not significantly associated with change of aortic plaque. Regarding ABPM variables, systolic ABPM variables including 24 hour, daytime and nighttime mean systolic BP were associated with progression of aortic atheroma, whereas diastolic BP variables were not associated with change of aortic atherosclerosis. 24 hour, daytime and nighttime mean systolic BP were significantly related to plaque progression even after adjusting for clinical parameters (p=0.007 for 24 hour and daytime SBP, p=0.003 for nighttime SBP).

Conclusions:
Systolic BP variables were associated with progression of aortic atheroma in patients with stroke, which suggests systolic BP control can be a key to suppress progression of aortic plaques.
Abstract 14602: Does Cancer Treatment Break Your Heart? A Linked Health Data Analysis of Thecharacteristics and Survival of Patients Who Have Developed Cardiovascular Disease Post Cancer Treatment
Authors: Clark Robyn A , Lui Saifei
Published: June 2023

Background:
Cancer treatment induced cardiotoxicity, can be a devastating outcome of cancer therapy. It is possible that a patient can survive cancer but develop cardiovascular disease (CVD).

Aim:
to determine whether there are differences in the characteristics of cancer patients who received potentially cardiotoxic cancer therapy and subsequently developed CVD and those who did not.

Methods:
This epidemiological study will comprise a retrospective analysis of de-identified linked health data sets, including the Integrated Activity Collection (ISAAC) of Hospital Separations, South Australian Cancer Registry (SACR), Northern Territory Cancer Registry (NTCR) and mortality (Births Deaths and Marriage Registry Data) and NT Hospital Separation data. The total population will be segregated in two distinct groups namely ‘Cancer with no HF’ and ‘Cancer with HF’ to compare the between group differences by demographic factors and medical history.

Results:
Of the (n=17,389) patients who received chemotherapy cancer treatment between July 2001-June 2017, 49% (8,530) were diagnosed with HF post cancer treatment( median age at cancer diagnosis 65 years; 58% male); crude mortality was 73% within the HF and cancer group; cause of death within this group was HF related 14%; cancer related 63%; other 22% compared to the non HF and cancer group ( median age at cancer diagnosis 58 years; 53% male) who had a mortality rate of 46%; 6.2% CVD related; 68.8% cancer related and 25% other.

Conclusion:
After adjusting for age, sex, tumour grade, cancer site and CVD admissions prior to cancer diagnosis patients with CVD and cancer had poorer outcomes.
Abstract 14626: Dissecting Out Risk Factors: A Case of Spontaneous Coronary Artery Dissection Without Traditional Risk Factors, in the Presence of Methamphetamine Use
Authors: Ali Mohammed , Nagamine Todd , Techasatian Witina , Gozun Maan Kathryn , Shah Parthav , Kuniyoshi Jason , Benavente Kevin , Zhang James , Yeo Jihun , Banerjee Dipanjan
Published: June 2023

Introduction:
Methamphetamine use is not a traditional risk factor for spontaneous coronary artery dissection (SCAD). There have been several case reports suggesting an association between methamphetamine use and SCAD.

Case:
We present a case of a 50-year-old female with a history of hypertension, hyperlipidemia, stroke, and active tobacco use who presented with substernal chest pain radiating to the back and abdomen with associated dyspnea and diaphoresis. The patient was also taking warfarin for a prior history of deep venous thrombosis. Her serum 5
th
generation troponin level was elevated to a peak of 1135 ng/L, and a 12-lead EKG showed ST-elevations not meeting STEMI criteria (1mm in V3, 2mm in V4, and 0.5mm in V5). Coronary angiography showed a short section of SCAD type 1 involving the mid portion of the LAD with TIMI 3 flow. There was no significant atherosclerotic disease throughout any of the vessels. The patient was managed conservatively with medical therapy and had resolution of her pain. CT-angiography of the chest, abdomen and pelvis was performed to rule out dissection involving the aorta and its branches and was unrevealing. Urine toxicology screening returned positive for methamphetamine. Given a lack of other traditional risk factors aside from gender, the patient was diagnosed with SCAD secondary to methamphetamine use.

Discussion:
Traditional risk factors for SCAD include female sex, fibromuscular dysplasia, connective tissue disease, multiparity (our patient was parity 1), and exogenous hormone use. Methamphetamine use as well as prescription amphetamines have been associated with SCAD in several case reports. SCAD tends to occur in women with an absence of risk factors for coronary artery disease. However, even in patients with multiple risk factors for atherosclerosis and an absence of risk factors for SCAD, SCAD should not be excluded in the differential when a history of amphetamine use is elicited.
Abstract 14647: Effects of an App-Based Exercise Intervention Program on Exercise Capacity for Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis
Authors: An Minjeong , Lee Yeonhu
Published: June 2023

Introduction:
Mobile-based healthcare is considered a strategy that can overcome time and space constraints and increase the participation rate of a heart health program; however, a review of the elements of exercise prescription, such as frequency, intensity, time, and type (FITT), has been insufficient. Therefore, a systematic review and meta-analysis were performed to identify the FITT elements of an app-based exercise heart health intervention that was effective in improving the exercise capacity of patients with Acute Coronary Syndrome (ACS).

Methods:
A literature search was conducted for papers published up to November 2021. We searched for randomized controlled trials (RCTs) evaluating the effectiveness of an exercise-based heart health program using a smartphone app for adult inpatients initially diagnosed with ACS, who received primary percutaneous coronary intervention or medication treatment. With the help of our librarians, we searched MEDLINE, EMBASE, and Cochrane CENTRAL. Literature selection, bias evaluation, and data collection were independently performed by two researchers. Cochrane Risk of Bias 2 was used to evaluate the quality of literature; the level of evidence was evaluated using GRADE, and CMA Version 3.0 was used for the meta-analysis. Effect size for exercise capacity was calculated using standardized mean difference.

Results:
Seven RCTs were identified. The study results suggested that using an app-based exercise heart health program was effective in improving the exercise capacity of patients in Phase III of cardiac rehabilitation post-ACS. As a confirmed exercise prescription factor, the app was found to be effective in improving exercise capacity when aerobic exercise was performed for approximately 30 minutes at least three to five times a week. The effect size for exercise capacity was 0.42 (95% CI, 0.24-0.60; I
2
, 45.00;
p
<.001). App-based exercise interventions was confirmed to be effective in improving exercise capacity compared to general heart health interventions.

Conclusions:
An app-based exercise heart health intervention is safe and effective in improving exercise capacity and encouraging post-ACS patients who are in Phase III of cardiac rehabilitation to start exercise after hospital discharge.
Abstract 14660: Truncating Variants in
MYBPC3
Cause Ubiquitin Proteasome System Dysfunction Related to Hypertrophic Cardiomyopathy in Human Induced Pluripotent Stem Cell Model
Authors: Yamamoto Yuta , Parikh Victoria N , Ashley Euan A
Published: June 2023

Introduction:
Hypertrophic cardiomyopathy (HCM) is the most common inherited monogenic cardiomyopathy. Cardiac myosin binding protein C (
MYBPC3
) is the most frequently mutated gene in this disease, and most pathogenic variants in
MYBPC3
are truncating variants including splice site variants. The ubiquitin proteasome system (UPS), a major intracellular protein degradation system, plays an important role in the heart. Although impairment of UPS is reportedly caused by truncated cMyBP-C, the underlying molecular mechanism causing HCM is largely unknown.

Hypothesis:
Truncating variants in
MYBPC3
lead to impaired UPS activity in human iPS cell-derived cardiomyocytes (hiPSC-CMs) and are associated with HCM phenotypes.

Methods:
Patient derived iPSC clones were generated from HCM patients with
MYBPC3
variants (IVS11-9G>A and IVS27+1G>A). Corrected isogenic control of IVS27+1G>A was generated by base editing. To evaluate UPS activity, we employed ubiquitin fusion degradation reporter, Ub-G76V-GFP, which provides fluorescence readout of UPS activity. BNP expression of hiPSC-CMs were evaluated by antibody labeling and fluorescence-activated cell sorting (FACS). Contractility and Ca
2+
transient were measured from single biopatterned hiPSC-CMs.

Results:
Both
MYBPC3
variant lines exhibited UPS impairment as reflected by increased GFP fluorescence compared to isogenic and healthy controls (Fig. A). IVS27+1G>A showed higher expression of BNP (Fig. B and C). Enhanced contractility and Ca
2+
handling abnormalities were observed in
MYBPC3
variant iPSC-CM lines as compared to control (Fig. D and E).

Conclusions:
Impairment of UPS activity may be associated with a marker of cellular hypertrophy, and contractility and Ca
2+
handling abnormalities in hiPSC-CMs with
MYBPC3
truncating variants. These findings support prior reports suggesting that decreased UPS activity contribute to the pathophysiological mechanism of HCM caused by truncating
MYBPC3
variants.
Abstract 14663: The Impact of Continuous Positive Airway Pressure for Sleep Apnea on Left Atrial Dilatation in Patients Receiving Catheter Ablation of Atrial Fibrillation
Authors: Tanaka Nobuaki , Okada Masato , Tanaka Koji , Hirao Yuko , Harada Shinichi , Kawahira Masatsugu , Koyama Yasushi , Fujii Kenshi , Heitaro Watanabe , OKAMURA ATSUNORI , Iwakura Katsuomi
Published: June 2023

Background Sleep apnea (SA) and left atrial dilatation (LA) are both risk factors for an arrhythmia recurrence after catheter ablation (CA) of atrial fibrillation (AF). Negative intrathoracic pressure fluctuations during an obstructive apnea episode may cause the left atrium to distend and stretch its wall. However, the impact of continuous positive airway pressure (CPAP) for SA on the reverse LA remodeling has not been elucidated. Methods This study was conducted under a retrospective, single-center, observational design. Data was derived from screening tests for sleep apnea, which were routinely performed in patients scheduled to receive CA of AF in our institution. The severity of the sleep apnea was evaluated by the apnea-hypopnea index (AHI). After excluding patients who were already diagnosed with sleep apnea, we enrolled 1232 consecutive patients who underwent multidetector computed tomography (MDCT) both before and 3-months after the CA of AF. The left atrial dilatation and volume reduction were evaluated by the left atrial minimum volume (LA min V) using 256-slice MDCT. Results The age was 65±11 years, 27.8% were females, and 46.0% had non-paroxysmal AF. The mean AHI was 20.2±15.2 and LA min V 79.1± 37.8ml (r=0.31, p<0.0001) before CA. LA dilatation was defined as an LA min V≥79.1ml. After an adjustment by an advanced age (≥65 years), non-paroxysmal AF, male sex, obesity, hypertension, diabetes, and congestive heart failure, SA (AHI≥5) was a significant predictor of LA dilatation before CA (odds ratio 2.83, 95% confidence interval 1.55-5.16, p=0.0007). After CA, 206 out of 1092 patients (18.9%) with SA started CPAP. SA patients with CPAPs had a greater LA min V reduction rate on the postprocedural CT than those without CPAP (26.2% vs. 20.5%, p=0.013). Conclusion Among the patients scheduled to receive catheter ablation of AF, SA was independently associated with left atrial dilatation. Patients who started CPAP treatment for SA had greater LA reverse remodeling at 3 months after the CA.
Abstract 14666: Coronary Arterial Calcification Influences Fractional Flow Reserve: Comparison of Guide Wire Type FFR With Vasodilator and FFRangio Without Vasodilator
Authors: Funabashi Nobusada , Misumi Kazuo
Published: June 2023

Introduction:
Fractional flow reserve (FFR) measures percutaneous coronary intervention (PCI) performance. FFR was determined by guide wire (GW)-type FFR. It is now evaluated by computed tomography (CT; FFRCT) or invasive coronary angiography (FFRangio; CathWorks, USA), whereby coronary arteries are traced on a conventional angiogram from three different angles to form three-dimensional images; the calculated FFR is FFRangio. In contrast to GW-type FFR, FFRangio does not need a vasodilator drug (e.g. nicorandil) load or GW. Hypothesis: Coronary calcification may influence the effect of vasodilator drugs, causing a difference between FFRangio and GW-type FFR depending on coronary calcium score (CCS).

Methods:
FFRangio and GW-type FFR (SJN, Zeon, ACIST) were simultaneously evaluated at catheter examinations in 11 coronary arteries from 9 patients before PCI (six males, mean age 72±11 years). Nicorandil (2 mg) was directly injected when measuring GW-type FFR. Cardiac CT was performed to measure CCS.

Results:
The correlation coefficients between FFR magnitude (=mean of FFRangio and GW-type FFR) and CCS in all vessels, and a vessel with FFR measurement, were -0.845 and -0.843, respectively. The correlation coefficients between difference in FFRangio minus GW-type FFR and CCS in all vessels, and a vessel with FFR measurement, were 0.627 and 0.752, respectively. The greater the CCS of both all vessels and a vessel in FFR measurements, the smaller the FFR. The greater the CCS of both all vessels and a vessel with FFR measurement, the greater the difference in FFRangio minus GW-type FFR (Figures). This may indicate the greater the CCS, the smaller the vasodilation effect of a direct nicorandil injection.

Conclusions:
Of GW-type FFR, FFRangio, and FFR CT, only GW-type FFR requires a vasodilator injection. Coronary arteries, known to cause blooming artifacts and impair the accuracy of FFRCT, also influence vasodilator effects, especially with borderline FFR (0.75-0.80).
Abstract 14673: The Effect of Increasing the Ultrasound Pulse Length on Sonoreperfusion Therapy
Authors: Yu Francois T.H. , Amjad Muhammad Wahab , Mohammed Soheb Anwar , Yu Gary , Chen Xucai , Pacella John
Published: June 2023

Background:
In recent years, long and short pulse ultrasound (US)-targeted microbubble cavitation (UTMC) has been shown to increase perfusion in healthy and ischemic skeletal muscle, in pre-clinical animal models of microvascular obstruction, and in the myocardium of patients presenting with acute myocardial infarction, and microvascular vasodilation played an important role in its efficacy. Our prior preliminary data suggested that long pulse US confers enhanced sonoreperfusion efficacy compared to short pulse US.

Objective:
In this study, we sought to definitively compare acoustic energy matched, long (5000 cycles) and short pulse (500 х 10 cycles, separated by 100 μs intervals) US (pressure of 1.5 MPa with an equivalent total number of acoustical cycles and at the same frequency (1 MHz)), in a rodent hindlimb model, with and without microvascular obstruction (MVO).

Results:
By quantifying perfusion using burst replenishment contrast enhanced US imaging, we found that: (1) long and short pulses result in different vasodilation kinetics in an intact hindlimb model. The long pulse causes an initial reduction in flow due to microvascular spasm that spontaneously resolved at 4-min, followed by sustained higher flow rates (~2-folds) compared to baseline, starting 10 min after therapy (
p
<0.05). The short pulse caused a short-lived ~2-fold increase in flow rate that peaked at 4-min (
p
<0.05), but without the initial microvascular spasm; (2) the sustained increase in perfusion during long pulse is not simply reactive hyperemia; and (3) both pulses are effective in reperfusion of MVO in our hindlimb model by restoring blood volume, but only the long pulse caused an increase in flow rate after treatment 2, compared to MVO (
p
<0.05). Histological analysis post UTMC with either pulse configuration indicates no evidence of tissue damage or hemorrhage.

Conclusions:
Our findings demonstrate that the microbubble oscillation induces vasodilation and therapeutic efficacy for the treatment of MVO can be tuned by varying pulse length; relative to short pulse US, longer pulses drive greater microbubble cavitation and more rapid microvascular flow rate restoration after MVO, warranting further optimization of the pulse length for sonoreperfusion therapy.
Abstract 14686: Prevalence and Predictors of Normotensive Shock in Intermediate-Risk Pulmonary Embolism
Authors: Bangalore Sripal
Published: June 2023

Introduction:
In patients presenting with pulmonary embolism (PE) and shock/hypotension (high-risk PE), immediate thrombolytic therapy or mechanical thrombectomy is recommended. However, the prevalence and predictors of normotensive shock in patients with intermediate-risk PE are not well defined.

Methods:
PE patients undergoing mechanical thrombectomy with the FlowTriever System (Inari Medical) were enrolled in the FLASH Registry. Patients were included in this analysis if they were intermediate-risk per ESC guidelines (i.e., normotensive) and had cardiac index (CI) measured pre- and post-thrombectomy. Invasive hemodynamics were measured pre- and post-thrombectomy and compared using paired data. Patients were grouped into those with normotensive shock (CI ≤ 2.2 l/min/m
2
) or without shock (CI > 2.2 l/min/m
2
). Multiple logistic regression was used to identify baseline predictors of normotensive shock. Safety outcomes through 30 days were recorded.

Results:
Out of 384 intermediate-risk PE patients, more than one-third (131, 34.1%) were in normotensive shock at baseline. The shock group had significantly lower BMI, higher RV/LV ratio, and higher rates of moderately/severely reduced RV function and concomitant DVT (Table). Significant predictors of shock included tachycardia, distal concomitant DVT, moderately/severely reduced RV function, and saddle PE. The normotensive shock group showed significant on-table improvement in CI and mean PA pressure post-thrombectomy (Figure). Safety profiles were not significantly different between groups, with similarly low rates of major adverse events and mortality through 30 days (Table).

Conclusion
Although identified as intermediate-risk, over one-third of patients had normotensive shock, suggesting they may be at risk of hemodynamic deterioration despite appearing stable. Treatment with mechanical thrombectomy improved patient hemodynamics on the table, with low rates of mortality in both groups.
Abstract 14690: Deep Learning Assisted Target Lesion Analysis Using Advanced Border Detection Algorithm of Intravascular Ultrasound
Authors: Kim Sang Wook , Park Kyung Teak , Jo Jun Hwan , Jung Moonki , Song Haegeun , Shin Seung Yong , Lee Sangyeub , Kim Nam Ki , KANG KI-WOON , CHO Sungsoo , Byeon Kyung Min , Won Ho Yeon , Cho Ounjung , Jeong Young-Hoon , Kim Hyue Mee , Lee Wang Soo , Lee Kwang Je , Kim Tae Ho , Kim Chee Jeon , Ahn Tae Hoon
Published: June 2023

The vessel-plaque interface detection and lesion length of coronary artery disease are still challenging using the deep learning with intravascular ultrasound (IVUS).
We used AI-based image segmentation technology to develop a deep learning model for classifying frames with IVUS-derived target lesion.
Methods. A total of 3,782 target lesion frames from 28 acute coronary syndrome(ACS) patients were randomized into training and test sets in a 2:1 ratio. The training algorithm was based on the measurement of the core lab. A segmentation model using non-local blocks was used to increase the similarity between pixels of the same class in a U-Net-based model. The edge detection was performed on the region of interest, and the detected edge was used as an aid in deriving the final segmentation result. And the morphological guided measurements were used to provide the information about the vessel area, lumen area, plaque burden and lesion length. Quantitative evaluation was conducted on four scales: Jaccard Measure (JM), Dice Similarity Coefficient (DSC), Hausdorff Distance (HD), and Percentage of Area Difference (PAD). And we compared the diagnostic accuracy to detect the vessel-plaque interface of the target lesion.
Results. In the training sample (1,256 IVUS frames of target lesion), and the test samples (1,072 IVUS frames of target lesion) were used for the proposed model. The external elastic membrane area (EEM), lumen area, plaque area and thrombus were assessed with the proposed algorithm. The measurement of EEM was DSC 0.99, JM 0.98, HD 0.06, and PAD 0.01. And the lumen also shows excellent performance with DSC 0.98, JM 0.97, HD 0.08, and PAD 0.01. In addition, the proposed model was compared with ground-truth for Thrombus, and showed high values of 0.88 for DSC, 0.83 for JM, 0.21 for HD, and 0.09 for PAD.
Conclusion. An advanced algorithm can accurately detect the vessel-plaque interface and estimated stent length of coronary artery disease with high reproducibility. F
Abstract 14698: Identifying Sources of Prostacyclin Outside the Vascular Wall and Their Contribution to Cardiovascular Protection
Authors: Lopes Pires Maria , Vinokurova Maria , Shala Fisnik , Ahmetaj-Shala Blerina , Armstrong Paul C , Herschman Harvey R , Mitchell Jane A , Kirkby Nicholas S
Published: June 2023

Introduction:
Prostacyclin is a key anti-thrombotic hormone synthesised through cyclooxygenase (COX) enzymes. Historically, its production has been almost universally associated with the endothelium however the role of non-vascular sources has not been systematically evaluated due to a lack of suitable tools. This has resulted in an underappreciation of its cardiovascular biology and role in other contexts.

Hypothesis:
We hypothesised that cells outside the vascular wall contribute to generation of prostacyclin which can enter the circulation to provide anti-thrombotic protection.

Methods:
Global, endothelial and fibroblast COX1 or COX2 knockout mice were studied alongside freshly isolated healthy human lung tissue and primary cell cultures. Prostacyclin levels in plasma and released from cells/tissue ex vivo were measured by ELISA. Individual cell populations were isolated by FACS. Thrombosis in vivo was measured using a FeCl
3
-carotid artery injury model.

Results:
Vascular endothelial COX1 deletion strongly reduced prostacyclin release from mouse aorta and heart, but not from isolated lung, colon, kidney or spleen (Fig A). This non-vascular prostacyclin required COX1 as it was abolished by global COX1 and not COX2 deletion. Freshly isolated lung fibroblasts exhibited greater prostacyclin synthesis than endothelial or other cell types (Fig B) and this was confirmed in primary human lung cell cultures. Deletion of COX1 from fibroblasts in mice reduced lung prostacyclin release (Fig C) and plasma prostacyclin levels (Fig D) and this was associated with accelerated thrombotic occlusion after carotid artery injury (Fig E).

Conclusions:
These findings define a new paradigm in prostacyclin biology in which fibroblast/non-vascular-derived prostacyclin works in parallel with endothelium-derived prostanoids to control thrombosis. This may have particular relevance to understanding how local diseases of the lung result in cardiovascular risk.
Abstract 147: Volunteer Responders Often Provide Emotional Support To Relatives Of Out-of-hospital Cardiac Arrest Patients Even After Arrival Of The Emergency Medical Services
Authors: Kragh Astrid Rolin , Gregers Mads Christian Tofte , Juul Grabmayr Anne , Kjoelbye Julie S , Jakobsen Louise K , Andelius Linn , Folke Fredrik , Malta Hansen Carolina
Published: June 2023

Introduction:
Volunteer responders (VR) are dispatched to OHCA to fetch an AED and provide CPR. However, often more than one volunteer responder arrives, allowing additional responders to handle tasks beyond resuscitative efforts. We aimed to assess which tasks dispatched VR performed during resuscitation attempts and the proportion of VR providing emotional support to patient relatives.

Method and Results:
This was an observational study with prospectively collected data from Denmark's national volunteer responder cohort between April 2020 and May 2022. We included 18,489 VR who accepted an alarm and arrived at a presumed cardiac arrest. All VR who received an alarm received a survey 90 minutes after, which included questions regarding their handling of tasks (response rate 86.1%). Of 18,489 volunteers, 6,612 (35.8%) arrived before EMS. Among all VR who arrived at the cardiac arrest scene, 3,424 (18.5%) performed CPR, 1,851 (10.0%) attached an AED, and 3,447 (18.6%) provided support for relatives. In univariate logistic regression models, VR provision of CPR was significantly associated with being healthcare educated (OR: 1.76, 95% CI: 1.61-1.93), police or firefighter (OR: 3.28, 95% CI: 2.96-3.64). Further, odds for CPR provision increased with recent CPR course (OR: 2.48, 95% CI: 2.09-2.93). VR provision of CPR was significantly associated with an increasing number of VR arriving before EMS. Odds for the provision of CPR were doubled in cases where three or more VR arrived before EMS (OR:6.06, 95% CI: 5.29-6.94) compared to cases where one VR arrived (OR: 3.15, 95% CI: 2.70-3.69). When VR arrived after EMS, 14.9 % provided support for relatives (Fig 1).

Conclusion:
Volunteer responders’ engagement in OHCA is associated with educational background and the number of volunteers arriving before EMS. Provision of support for relatives is the most frequently handled task, even at arrival after the EMS.
Abstract 14706: Poor Medication Access as a Driver of Excess Heart Failure Readmissions in Deprived Neighborhoods
Authors: Gangavelli Apoorva , Liu Zihao , Wang Jeffrey , Okoh Alexis K , Steinberg Rebecca , Patel Krishan , Patel Shivani , Dickert Neal W , Morris Alanna A
Published: June 2023

Background:
Disparities in heart failure (HF) outcomes exist in the United States, in part, due to social determinants of health. Individuals from racial and ethnic minority groups report the highest rates of cost-related delays in care and worse access to high-quality medical therapy. We have previously demonstrated that individuals residing in more deprived neighborhoods experience higher readmissions, and Black patients are more likely to reside in deprived neighborhoods than White patients. Here, we engaged patients from the most deprived neighborhoods to understand drivers of excess readmission from the patient perspective.

Methods:
We conducted semi-structured in-depth interviews with 25 patients (mean age 61 ± 9 years, 96% Black, 40% female) readmitted with HF at Emory Healthcare hospitals, and living in a neighborhood in the top 10% of the Social Deprivation Index. Qualitative descriptive analysis of the interviews was performed using a multilevel coding strategy.

Results:
Patients in this cohort had a mean EF 39 ± 19%, and experienced 3.2 ± 2.5 readmissions in the preceding 12 months. Most patients (84%) highlighted lack of access to medications as a driver of hospital readmission. Representative quotes from individual patients are highlighted in the
Table.
Patients reported the etiology of their lack of medication access included medication costs (64%), only having access to re-fills through the emergency room or hospitalization (36%), low health literacy (12%), and limited access to transportation (8%).

Conclusion:
Lack of access to medications for patients with HF who live in socioeconomically deprived neighborhoods poses a challenge to reducing the burden of HF. Providing cost-effective and sustainable access to medications for patients with HF from low resource settings is a potential solution to decrease the number of HF hospitalization and readmissions in this vulnerable patient population.
Abstract 14713: Long-Term Clinical Outcomes in Patients With Chronic Total Occlusion of Single Coronary Artery Treated With Percutaneous Coronary Intervention versus Optimal Medical Therapy: A Ten-Year Follow Up Study
Authors: Kim Sungeun , Park Taek Kyu , Choi Seung-Hyuk
Published: June 2023

INTRODUCTION : Only limited data are available and long term follow up studies are insufficient about optimal treatment in patients with chronic total occlusion of a single coronary artery.METHODS : A total of 2,024 patients with CTO were retrospectively enrolled in Samsung Medical Center CTO registry between March 2003 and February 2012 and followed-up for 10 years. Patients underwent coronary artery bypass graft (n = 477) and Patients with multi-vessel CTO (n = 1,112) were excluded. Finally patients with chronic total occlusion of a single coronary artery (n = 435) were analyzed. Divided into two groups, optimal medical group (OMT, n = 147) and percutaneous coronary intervention group (PCI, n = 288) in accordance with initial treatment strategy. Cox regression analysis and propensity score matching was performed to adjust for confounding factors. Primary outcome was cardiac death.RESULT : During the follow up 10 years, we identified that there were no significant differences between OMT group and PCI group in rate of cardiac death (adjusted HR, 0.57 [95% CI, 0.26-1.24]; P=0.16) as well as rate of major adverse cardiac event (adjusted HR, 0.79 [95% CI, 0.52-1.19]; P=0.26) . After propensity score matching analyses, OMT group and PCI group still have no significant differences in rate of cardiac death (adjusted HR, 0.54 [95% CI, 0.24-1.19]; P=0.13) and rate of MACE (adjusted HR, 0.97 [95% CI, 0.62-1.52]; P=0.89).CONCLUSION : This retrospective observational study supported that as an initial treatment strategy in patients of single vessel CTO, PCI did not decrease the rate of cardiac death or MACE.

KEYWORD : Chronic total occlusion, Optimal medical treatment, Percutaneous coronary intervention
Abstract 14718: Using Renal-Specific Cyclo-Oxygenase-2-Deficient Mice to Understand the Pro-Thrombotic Effects of Non-Steroidal Anti-Inflammatory Drugs
Authors: Lopes Pires Maria , Ferreira Plinio , Shala Fisnik , Cypaite Neringa , Vinokurova Maria , Want Elizabeth , Herschman Harvey , Mitchell Jane A , Kirkby Nicholas
Published: June 2023

Introduction:
Non-steroidal anti-inflammatory drugs (NSAIDs) work by inhibiting the enzyme cyclooxygenase (COX)2 but their use increases thrombotic risk. We have shown that COX2 inhibition increases plasma methylarginines ADMA and LNMMA in mice and man. Methylarginines are controlled in the kidney but circulate causing inhibition of anti-thrombotic vascular NO by competing with L-arginine for the active site of eNOS. However, the causative links between renal COX2 (which is expressed predominately in fibroblasts), methylarginines and thrombosis remain unproven.

Hypothesis:
Here we hypothesised that deletion of COX2 from fibroblasts would result in a renal-specific COX2-deficiency and be sufficient to increase methylarginine levels and drive vascular NO dysfunction and a pro-thrombotic phenotype.

Methods:
Fibroblast COX2-deficient mice were generated from Fsp1-Cre and Ptgs2
flox
strains. COX2 levels were measured by RT-qPCR, methylarginines by LC/MS/MS, vascular NO function as acetylcholine-induced dilation by myography and thrombosis in vivo after FeCl
3
-carotid injury.

Results:
Fibroblast COX2-deficient mice showed reduced COX2 expression in the renal medulla (Fig A) but not renal cortex, aorta, lung, colon, thymus or brain. This was associated with increased plasma ADMA and LNMMA levels (Fig B) and reduced NO-dependent dilatation of carotid arteries (Fig C). Fibroblast COX2-deficiency accelerated thrombosis after carotid artery injury which could be reversed by pre-treating animals with L-arginine (50mg/kg; 5 days) which displaces methylarginines from eNOS (Fig D).

Conclusions:
These data provide the first direct demonstration that renal COX2 regulates methylarginine levels to control systemic endothelial and thrombotic function. As such, they indicate that inhibition of renal COX2 contributes to the thrombotic risk seen in patients taking NSAIDs and suggest L-arginine supplementation as a potential rescue therapy to mitigate this.
Abstract 14719: Erk5 S496 Phosphorylation, but Not Erk5 Kinase Activation, Promotes Senescence-Associated Cell Growth (sacg) and Inflammation of Myeloid Cells and Atherosclerosis via Upregulating Sumoylation at a Novel Site (k518) on Nrf2 and Aryl Hydrocarbon Receptor
Authors: Kotla Sivareddy , Imanishi Masaki , Li Shengyu , Zhang Aijun , Ko Kyung A , Samanthapudi Venkata Subrahman K , Lee Ling-Ling , Herrmann Joerg , Lin Steven , Shoykhet Michael N , Shen Ying H , Schadler Keri , Nguyen Minh T , Gupte Anisha A , Reyes-Gibby Cielito , Yeung Sai-Ching , Palaskas Nicolas L , Cooke John P , Pownall Henry J , Yoshimoto Momoko , Fujiwra Keigi , Hamilton Dale , Burks Jared K , Wang Guangyu , Le Nhat Tu T , Abe Junichi
Published: June 2023

Senescence induced by various stresses reprograms cancer cells to acquire senescence-associated (SA) cell growth (SACG), which allows them to escape senescence-induced cell cycle arrest with enhanced growth potential. ERK5 is a dual kinase-transcription factor, containing an N-terminal kinase domain and transactivation domains in the C-terminal half. Recent data have raised questions regarding the functional role of ERK5 kinase inhibitors in cancer and inflammatory diseases. We aimed to investigate how ERK5 reprograms myeloid cells (MC) to the SA secretory phenotype (SASP) and SACG, consequently leading to atherosclerosis (AthS). AthS was inhibited in ERK5 S496A knock-in (KI) mice. Single-cell analysis of p53 and Ki67 with imaging mass cytometry revealed three groups of MCs with different p53 and Ki67 expression patterns in the plaque. One group showed that p53 and Ki67 were co-expressed lineally, suggesting that this group of cells escaped from the growth-suppression effects of p53, which is also known as a senescence marker. The % of ERK5 S496A KI cells in this group was significantly lower than in wild-type (WT). Also, we found an increase of SA β-gal (SAβ-gal)
+
Ki67
+
and 53BP1
+
Ki67
+
cells in bone narrow-derived macrophage (BMDMs) isolated from hypercholesterolemia (H-chol) WT mice, suggesting H-chol-induced MC SACG. MC SACG were significantly inhibited in ERK5 S496A KI mice, supporting the role of ERK5 S496 phosphorylation on SACG. RNA sequencing analysis identified the ERK5 S496 phosphorylation-dependent AHR induction by H-chol, and AHR depletion significantly inhibited SACG. We also discovered a critical effect of ERK5 S496 phosphorylation on SUMOylation at a novel site of NRF2 (i.e., K518), which inhibited NRF2 transcriptional activity without affecting ERK5 kinase activity and antagonized oxidized LDL (oxLDL)-induced SASP. Specific ERK5 kinase inhibitors (AX15836 and XMD8-92) inhibited oxLDL-induced ERK5 S496 phosphorylation, suggesting that ERK5 S496 phosphorylation was involved at least in part of the effects of these inhibitors. We have discovered a novel mechanism in which ERK5 S496 phosphorylation directly inhibits NRF2 activity by upregulating NRF2 K518 SUMOylation and AHR induction, subsequently inducing SACG and AthS.
Abstract 14721: Association of Non-Surgical Weight Loss With Speckle-Tracking Strain Parameters
Authors: Panday Vinay B , Sia Ching-hui , Sik Yin Tan , Kong William , Poh Kian-Keong
Published: June 2023

Introduction
Several studies have demonstrated that surgical weight loss improves myocardial mechanics as measured by speckle-tracking imaging. The studies, however, have mostly been conducted in morbidly obese Caucasian populations with an average body mass index (BMI) of around 40 kg/m2. To our knowledge, no study has examined whether non-surgical weight loss can improve myocardial mechanics in the less morbidly obese.

Hypothesis
We hypothesized that non-surgical weight loss would improve strain parameters in less morbidly obese patients.

Methods
66 patients were recruited. Participants underwent a 16-week lifestyle intervention (LSI) programme. LSI consisted of a) dietary interventions involving regular consultations with the dietician and meal planning and b) exercise prescription with pedometers Echocardiography with speckle tracking was performed at baseline and post-intervention. Paired analysis using paired T-test evaluating changes in weight and strain parameters were conducted after intervention.

Results
The primary outcome was improvement in strain parameters after weight loss. Table 1 depicts the characteristics of the participants and the change in strain parameters. Participants attained significant weight loss after LSI ( 28.2 +/- 2.66 kg/m
2
vs 25.8 +/- 2.84 kg/m
2
, p =0.001). There was a significant reduction in waist and hip circumference (90.7 +/- 7.64 cm vs 83.62 +/- 7.13 cm, p =0.01) and (103.28 +/- 2.03 cm vs 97.74 +/- 6.24 cm, p=0.01) respectively. However this was not associated with improvement in strain parameters of the left atrium (51.456 +/- 11.24 vs 48.78 +/- 19.09, p =0.190) , left ventricle (-22.05 +/- 2.98 vs 22.77 +/- 3.21, p= 0.125) and right ventricle (-21.56 +/- 3.32 vs -22.02 +/- 3.59, p = 0.404).

Conclusion
Non-surgical weight loss was not associated with an improvement in echocardiographic speckle-tracking strain parameters.
Abstract 14782: Expression of Ngf Shrna in the Left Atrial Appendage Alone is Sufficient to Attenuate Global Left Atrial Parasympathetic and Sympathetic Nerve Sprouting and Resulting Development of Persistent Atrial Fibrillation in a Canine Model
Authors: Pfenniger Anna , Yoo Shin , Johnson David , Zhang Wenwei , Panni Azaria , Burrell Amy , Mandava Suman , Rottmann Markus , Passman Rod S , Knight Bradley P , Arora Rishi
Published: June 2023

Introduction:
The autonomic nervous system plays a major role in development of atrial fibrillation (AF), with evidence of marked autonomic remodeling in a canine rapid atrial pacing (RAP) model of AF. Nerve growth factor (NGF), a neurotrophin essential for peripheral neuron growth, was upregulated in fibrillating atria, particularly in the left atrial appendage (LAA).

Hypothesis:
Inhibiting NGF signaling in the entire atria or the LAA alone can prevent the development of AF.

Methods:
NGF shRNA was injected in both atria or in the LAA of dogs followed by electroporation to facilitate gene delivery. Animals were subjected to RAP for up to 12 weeks. Duration of AF was recorded. At terminal EP study, residual AF electrograms were recorded in the posterior left atrium, left atrial free wall and LAA for analysis of AF characteristics. Tissue of each region was used for IHC with markers for parasympathetic (acetylcholinesterase) or sympathetic nerves (dopamine beta-hydroxylase).

Results:
Controls (n=10) developed persistent AF (>8 hours) after a median of 14 days. In contrast, pan-atrial NGF shRNA animals (n=4) never developed this burden of AF. Residual AF was less fractionated (longer fractionation interval), more organized (higher organization index and lower Shannon's entropy) and more homogeneous (coefficient of variation of dominant frequency). RAP-induced nerve bundle hypertrophy and atrial myocardium hyperinnervation was significantly attenuated in pan-atrial NGF shRNA dogs. Importantly, these findings were reproduced when NGF shRNA injection was limited to the LAA alone (n=4), with prevention of development of persistent AF, and global attenuation of left atrial hyperinnervation.

Conclusion:
Targeted inhibition of atrial autonomic remodeling by NGF shRNA prevents development of persistent AF. NGF Inhibition in the LAA alone is sufficient to attenuate global atrial autonomic remodeling. This approach may lead to a novel, mechanism-guided therapy for AF.
Abstract 14787: Quantification of Flow and Biomechanics by Echocardiography (echo) in the Fetal Single Ventricle (sv)
Authors: Meyers Brett A , Bhattacharya Sayantan , Brindise Melissa , Loke Yue-Hin , Payne Ronald M , Vlachos Pavlos
Published: June 2023

Introduction:
Echo-based ventricular flow and biomechanical analysis provides novel measurements of SV function that can be assessed serially. However, this analysis has not been applied to clinical studies. This study demonstrates a new workflow to measure ventricular flow and biomechanics from apical 4-chamber imaging for hypoplastic left heart syndrome [HLHS] patients and age-matched controls.

Methods:
We retrospectively collected echos at 33 weeks gestation prenatally and 7 days post-birth postnatally. Color Doppler echo of the LV/RV were evaluated using an in-house vector flow reconstruction algorithm, quantifying energy loss [EL] and vortex strength [VS]. B-mode echo of the LV/RV were evaluated for parameters including cardiac output [CO] and global longitudinal strain [GLS].

Results:
9 HLHS subjects and 11 age-matched controls were included. Prenatal HLHS patients exhibited elevated CO, EL, and VS (p<0.01) but proportional GLS compared to the control LV/RV. The parameters serially increased postnatally (p<0.01), consistent with transitional physiology. GLS in HLHS was differentiable from the normal RV only in postnatal studies, resembling normal LV values.

Conclusions:
Altered ventricular flow and biomechanics were observed for HLHS patients compared to controls during early life. These novel parameters can be serially evaluated using conventional echo imaging. We will perform longitudinal studies of this HLHS cohort as they progress through surgical palliation to fully understand how our integrated workflow can better inform SV patient care.

Figure 1: Left – Comparison of ventricular flow and biomechanical markers between HLHS and control subjects, for prenatal (fetal) and postnatal (neonatal) ages. Right – Ventricular flow patterns for HLHS and control subjects for different ages.
Abstract 14791: Evaluation of Cardiac Size, Shape and Function in Fetuses With Coarctation of the Aorta by Fetal Heart Quantitative Technique
Authors: Liu Juanjuan , Cao Haiyan , Hong Liu , Zhang Li , Xie Mingxing
Published: June 2023

Introduction:
This study aimed to evaluate the size and shape of the four-chamber view (4CV) and right and left ventricles (RV and LV) as well as the function of the RV and LV in fetuses with coarctation of the aorta (CoA) using fetal heart quantitative (Fetal HQ) technique.

Methods:
A total of 67 CoA fetuses and 67 gestational age-matched controls were included. Fetal HQ technique was used to obtain the 4CV end-diastolic (ED) width, length, area, and global sphericity index (GSI), RV and LV 24-segment ED diameter (EDD), 24-segment sphericity index (SI), area, and the following functional parameters: (1) fractional area change (FAC); (2) global longitudinal strain (GLS); (3) 24-segment transverse fractional shortening (FS); (4) LV ejection fraction (LVEF), LV ED volume (LVEDV), LV stroke volume (LVSV) and LV output (LVO).

Results:
Compared with normal controls, the Z-score of 4CV ED width was increased (
P
< 0.05), while the GSI was decreased (
P
< 0.05) in fetuses with CoA. However, there were no significant differences in the Z-scores of 4CV ED length and area between two groups (both
P
> 0.05) The RV 24-segment EDD Z-scores, RV area Z-score as well as the RV/LV 24-segment EDD were significantly higher in CoA fetuses than in controls (all
P
< 0.05). In contrast, the LV 24-segment EDD Z-scores and area Z-score were significantly lower in fetuses with CoA (
P
< 0.05). The 24-segment SIs of the LV were significantly higher, while the 24-segment SIs of the RV were significantly lower in CoA group (all
P
< 0.05). CoA fetuses presented lower GLS, FAC and 24-segment FSs for both RV and LV when compared with normal controls (all
P
< 0.05). In addition, LVEF, LVEDV Z-score, LVSV Z-score and LVO Z-score were all decreased in CoA fetuses (all P < 0.05).

Conclusions:
In fetuses with CoA, the 4CV was increased in width and spherical in shape. The LV area and width were decreased, while the transverse width and area of RV was increased. Abnormal SIs reflected a flatter LV and a more spherical RV. RV and LV global, longitudinal, and transverse contractility were all depressed. Fetal HQ can be used to quantitatively analyze cardiac size, shape and function in CoA fetuses, which may improve prenatal diagnosis of CoA.
Abstract 14793: The Mediating Effect of Resilience on the Relationship Between Self-Care Activation, Hope, and Medication Adherence in a Diverse Sample of Adults With Heart Failure
Authors: Meraz Rebecca , McGee Jocelyn , Perry Elizabeth , Ke Weiming , Osteen Kathryn A
Published: June 2023

Background:
Despite decades of research and advances in treatment, medication adherence in those with heart failure remains suboptimal. Recent research suggests that self-care activation and positive psychological characteristics can enhance medication adherence, yet little is known about how these factors and medication adherence are related in persons with heart failure.

Objective:
The purpose of this study was to investigate whether the effects of self-care activation and hope on medication adherence are mediated by resilience in persons with heart failure.

Methods:
This study used a prospective, cross-sectional design. Regression and mediation analyses were used to examine if resilience mediates the effects of activation on medication adherence. A nationwide, diverse sample was recruited for this study.

Results:
Of the 174 participants, 51% were female, 48% were persons of color (POC) and the mean age was 62 years. Higher activation (B = -.023, p = .039) and hope (B = -.063, p = .011) were associated with better medication adherence. The effects of activation and hope on medication adherence were completely mediated by resilience. Indirect effect accounts for 17.4% of the total effect for activation and 71.4% for hope.

Conclusion:
Resilience could be a potential mechanism by which activation and hope could improve medication adherence in persons with heart failure. Thus, resilience may have a significant influence on medication adherence. More research is needed to understand the connection between resilience and medication adherence.