bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10606: The Increase of Myocardial Echogenicity Using Intracardiac Echography During Radiofrequency Ablation is an Effective Ablation Indicator
Authors: Mine Takanao , Sugitani Miho , Kogame Takehiro , Kitagaki Ryo , Fukuhara Eiji , Ishihara Masaharu
Published: June 2023

Introduction:
The increase of myocardial echogenicity (iME) is sometimes observed by intracardiac echography (ICE) during radiofrequency ablation (RFA), and the phenomenon has also been reported as a predictor of steam pop. However, the mechanism of iME caused by RFA remains unclear.

Methods:
We retrospectively studied 112 consecutive patients (age 70±9 years, 74 male) who underwent cavotricuspid isthmus (CTI) ablation. The changes in myocardial tissue during RFA were observed using ICE in 5.3 ± 1.4 points in each patient. 415 out of 590 ablation points were evaluable with ICE, and the iME during RFA were classified into three degrees (grade I: no change, II: mild, III: high brightness) by three independent observers who did not know clinical data. The voltage of myocardial amplitude and the myocardial wall thickness before and after RFA, and the lesion size index (LSI) incorporating contact force were measured at all RFA points.

Results:
RFA points were classified into 128 grade I of iME, 150 grade II, and 137 grade III. The iME during RFA were associated with reduced voltage of myocardial amplitude (grade I -0.22±0.44mV, II -0.29±0.47mV, III -0.38±0.47mV, P=0.0147), decreased rate of the voltage (grade I -14%, II -25%, III -44%, P=0.0131), and higher LSI (grade I 4.5±0.8mV, II 4.7±0.8mV, III 4.8±0.8, P=0.0207) (Figure). The higher LSI was associated with the decreased rate of the voltage (P=0.0491), but not with the voltage change of myocardial amplitude. On multivariate analysis, the iME during RFA was independently associated with the decreased rate of the voltage (P=0.0214). The iME was not related to the change in myocardial wall thickness before and after RFA, ablation sites (near tricuspid annulus side, middle part, or inferior vena cava side), and morphology of cavo-tricuspid isthmus. No steam pop phenomenon was observed.

Conclusions:
The iME during RFA is related to the decrease in myocardial amplitude due to RFA, and possibly be an effective ablation indicator.
Abstract 10664: Association of Unfavorable Social Determinants of Health With Stroke/TIA and Vascular Risk Factors: Results From the Hispanic Community Health Study/Study of Latinos
Authors: Trifan Gabriela , Gallo Linda , lamar melissa , Garcia Olga , Perreira Krista , Pirzada Amber , Talavera Gregory A , Wassertheil-Smoller Sylvia W , Isasi Carmen , Cai Jianwen , Daviglus Martha L , Testai Fernando
Published: June 2023

Introduction:
Social Determinants of Health (SDOH) contribute to the development of diseases and disproportionally affect minoritized groups. There is a paucity of information describing the relationship between SDOH, stroke/TIA and vascular risk factors (VRFs) in Hispanics/Latinos.

Hypothesis:
Unfavorable SDOH are associated with self-reported stroke/TIA and with increased VRFs.

Methods:
Cross-sectional data from cohort study of Hispanic Community Health Study/Study of Latinos (2014-2017). SDOH were assessed using questionnaires and previously validated scales. VRFs were hypertension, diabetes mellitus, hypercholesterolemia, smoking, at-risk alcohol use, and obesity. We investigated the association between the SDOH (individually and as count) and stroke/TIA using weighted complex survey multivariable logistic and linear regression analyses.

Results:
For individuals with stroke/TIA (weighted n=388), the mean age (58.9, 95% CI=56.4-61.5) differed from those without stroke/TIA (weighted n=11,210; 46.8, 95% CI=46.3-47.4). In bivariate analysis, income <$20,000, education less than high school, no health insurance, perceived discrimination, not retired and not currently employed, upper tertile for chronic stress, and lower tertiles for social support and language- and social-based acculturation were associated with stroke/TIA and used in further analysis. Participants were grouped into 5 categories based on the distribution of SDOH (≤1, 2, 3, 4 and ≥5 SDOH). Increasing number of SDOH was directly associated with the odds of each individual VRFs investigated (except for at-risk alcohol) and VRF count (β=0.11, 95% CI=0.09-0.14). After adjustment for confounders, the odds of stroke/TIA increased 2.3 times in individuals with three SDOH (95% CI 1.6-3.2) and 2.7 times (95% CI 1.9-3.7) for those with ≥5 SDOH, compared to those with ≤1 SDOH. In final model, income, discrimination, social support, chronic stress, and employment status were individually associated with higher odds of stroke/TIA.

Conclusions:
Increased number of SDOH increased odds for stroke/TIA and VRFs. The association between SDOH and stroke/TIA remained significant after adjustment for VRFs, suggesting the participation of additional mechanisms of disease.
Abstract 10670: Impact of Virtual Interviewing on Geographic Placement in the Cardiology Fellowship Match
Authors: Hasnie Usman A , Hasnie Ammar , estrada carlos , WEISSMAN Gaby , Williams Winter , Lloyd Steven G
Published: June 2023

Introduction:
Virtual interviewing for cardiology fellowship was instituted in the 2021 fellowship application cycle due to the COVID-19 pandemic and restricted travel. It is unknown what impact this has had on geographic patterns of fellow-training program matching. Our aim was to determine if there was a significant difference in the geographic placement in the cardiology fellowship match based on virtual interviews compared to prior years with in-person interviewing.

Methods:
All U.S. based accredited cardiovascular disease fellowship programs that participated in the 2019-2021 fellowship match cycles were identified. Those that had publicly available data regarding fellow residency training and training year were included. Each fellow was categorized based on their fellowship program and residency training as from the same program, from the same state, from the same region or from a different region. These were mutually exclusive categories.

Results:
Of the 236 eligible programs, 118 programs (50%) had available data for the 2019-2021 application cycles. Cumulatively n=1787 total fellows were identified. Compared to the pre-virtual cohort (n=1178 matched fellows) there was no difference in the geographic placement during the 2021 virtual cycle (n=609 matched fellows) including the proportion that matched at the same program (30.6% vs 31.5%, p=0.738), in the same state (13% vs 13.8%, p=0.719), same region (24.2% vs 19.7%, p=0.164), or different region (35% vs 33.1%, p=0.274). There was also no difference when stratified by small, medium, or large program size or geographic region.

Conclusions:
The use of virtual interviewing in the 2021 cardiology fellowship application cycle did not result in a significant difference in the geographic placement of fellows. Further study is needed to evaluate the impact of virtual interviewing and optimize its use in fellowship recruitment.
Abstract 10726: Cardiomyocyte Targeting Peptide to Deliver Amiodarone
Authors: Zahid Maliha , Weber Beth , Yurko Ray , Islam Kazi , Salama Guy
Published: June 2023

Introduction:
Amiodarone remains underutilized as an anti-arrhythmic due to significant off-target toxicities with long-term use. We hypothesized that the required dose could be minimized by targeting amiodarone to cardiomyocytes by utilizing a cardiomyocyte targeting peptide (CTP).

Methods:
CTP (APWHLSSQYSRT) was conjugated to amiodarone via a disulfide bond, HPLC purified, characterized by MALDI/TOF, and stability at 37°C assessed using serial HPLCs over 21 days. Adult, male guinea pigs (GP; n=4/group) were injected intraperitoneally daily with vehicle (7 days), amiodarone (7 days; 80mg/Kg), 1/10
th
the molar dose of CTP-amiodarone (5 days), or CTP (5 days), followed by euthanasia, hearts excised, perfused on a Langendorff apparatus with Tyrode’s solution, and placed in a custom-designed chamber blebbistatin (5 μM) to minimize contractions. Bolus injections of voltage (RH237) and Ca
2+
-indicator dye (Rhod-2/AM) were injected to simultaneously map cardiac action potentials (APs) and Ca
2+
transients (CaT), at 610-750nm and 570-595nm, respectively with 2 CMOS cameras, followed by pacing at 250ms to measure conduction velocity (CV), AP and CaT durations (at 90% recovery).

Results:
CTP-amiodarone produced a single HPLC peak at 16mins that remained stable for 21 days. CTP-amiodarone and amiodarone decreased conduction velocities in myocytes significantly compared to control GPs (0.92±0.05, 0.87±0.08ms, vs. 1.00±0.03m/s respectively, p<0.001). Amiodarone increased AP duration (192±5ms vs. 175±8ms for vehicle, p=0.0025), while CTP-amiodarone decreased it significantly (157±16ms, p=0.0136), similar to CTP alone (155±13, p=0.0039). Both amiodarone and CTP-amiodarone significantly decreased CaTs compared to vehicle treated GPs. CTP-amiodarone and CTP decreased CaTs to an extent greater than amiodarone alone (p<0.001).

Conclusions:
Our data suggests that amiodarone can be stably covalently linked to CTP, which is able to deliver amiodarone to cardiomyocytes in vivo in GPs, at 1/10
th
the dose of amiodarone needed to produce comparable slowing of CVs. The ability of CTP alone to decrease AP durations and CaTs was a surprise finding and merits further study to fully characterize the anti-arrhythmic actions of the CTP-amiodarone conjugate.
Abstract 10739: Impact of Cardiac Device Implantation in Elderly Japanese Patients With Heart Failure as Primary Prevention-A Post Hoc Analysis of the HINODE Trial
Authors: Enomoto Yoshinari , nakamura keijiro , Moroi Masao , Nakamura Masato , Aonuma Kazutaka , Simon Torri , Kayser Torsten , Ikeda Takanori
Published: June 2023

Introduction:
Despite increase in the incidence of chronic heart failure (HF) and sudden cardia death (SCD), the current use of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) in Japan is much lower than in Western countries. The HF Indication and SCD Prevention Trial Japan (HINODE) was designed to prospectively assess the rate of mortality, appropriately treated ventricular arrhythmias (VA) and heart failure (HF) for comparison with references from historical landmark trial MADIT-RIT in Japanese patients.

Hypothesis:
This sub analysis of HINODE evaluates the impact of ICD or CRT implantation in elderly Japanese patients concomitant with higher risk of heart failure.

Methods:
After treatment decisions following contemporary practice in Japan, patients were prospectively enrolled into four cohorts: (1) ICD (2) CRT with defibrillator (CRT-D) (3) standard medical therapy (‘non-device’) (4) pacing (indicated for CRT; received pacemaker or CRT pacing). We compared the all-cause mortality between elderly and non-elderly patients with elderly defined as age>70 at the time of study enrollment.

Results:
The HINODE study enrolled 354 patients (191 elderly) followed for 19.6 ± 6.5 months with a minimum of 12 months and an absolute death rate of 11.0%. The estimated survival rate for device recipients (n=239) through 24 months was 86.1% (97.5% LCL: 79.8%) with no significant difference for elderly vs non-elderly patients (HR 1.97, 95%CI: 0.86-4.54). Analysis within cohorts showed increased risk of all-cause mortality for elderly with an ICD compared to non-elderly with an ICD (HR 5.09 95% CI: 1.1-23.6). However, ICD cohort excluding those with CRT-D indication showed no significant difference (HR 3.70, 95% CI: 0.75-18.35). No significant difference showed in other cohorts: CRT-D (HR 1.53 95% CI: 0.34-6.84) or pacing (HR 0.84, 95%CI: 0.2-3.5). Ventricular event free rate in ICD and CRT-D patients also had no difference (HR 0.84 95% CI: 0.31-2.25)

Conclusions:
Although elderly patients might be associated with higher risk of mortality in general, benefit of device therapy is comparable to non-elderly patients. We might consider device therapy despite age as a standalone risk in contemporary Japanese clinical practice.
Abstract 10744: Predictive Value of Calcium Volume Measurement Determined by Computed Tomography for Paravalvular Leakage After Transcatheter Aortic Valve Implantation
Authors: Isomatsu Daisuke , Sato Akihiko , Muto Yuki , Abe Satoshi , Misaka Tomofumi , Oikawa Masayoshi , KOBAYASHI ATSUSHI , Yoshihisa Akiomi , Nakazato Kazuhiko , Ishida Takafumi , Sekino Hirofumi , Fukushima Kenji , Ito Hiroshi , Takeishi Yasuchika
Published: June 2023

Background:
Paravalvular leakage (PVL) is a frequent complication after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS), and is related to adverse prognosis. We aimed to investigate whether aortic valve calcium volume (Ca-Vol) measured by preoperative cardiac computed tomography (CT) had a predictive value for PVL.

Methods and Results:
We analyzed consecutive 43 patients underwent TAVI using third-generation self-expandable valve (Evolut PRO
®︎
) for severe AS with tricuspid valve. Among 43 patients, PVL was detected in 8 cases (18.6%) after TAVI. PVL was defined as moderate or severe regurgitation determined by transthoracic echocardiography. We analyzed preoperative cardiac CT (Fig 1), and measured total Ca-Vol in aortic valve and Ca-Vol in each cusp (non-coronary cusp [NCC], right-coronary cusp [RCC], and left-coronary cusp [LCC]). The threshold of CT value for calcium structure was determined at 500 Hounsfield Units as previously reported. Total Ca-Vol was significantly higher in the PVL group than in the non-PVL group (3.9 ± 2.8 vs. 2.1 ± 1.0 ml, P = 0.004). Ca-Vols in each cusp were also significantly higher in the PVL group than in the non-PVL group (NCC, 1.5 ± 1.0 vs. 0.8 ± 0.4 ml, P = 0.004; RCC, 1.2 ± 1.1 vs. 0.6 ± 0.3 ml, P = 0.007; and LCC, 1.1 ± 0.8 vs. 0.7 ± 0.4 ml, P = 0.021). Univariate logistic regression analysis for PVL indicated that total Ca-Vol and NCC Ca-Vol were predictors for PVL (total Ca-Vol, OR 2.0, 95% CI 1.0-4.1, P = 0.042; NCC Ca-Vol, OR 5.1, 95% CI 1.2-22.2, P = 0.031). By the receiver operating characteristic curve analysis of Ca-Vol for prediction of PVL, the optimal cut off values were 2.3 ml of total Ca-Vol and 0.8 ml of NCC Ca-Vol (Fig 2; AUC = 0.75 and 0.78, sensitivity 0.75 and 0.88, specificity 0.63 and 0.54, respectively).

Conclusion:
Total Ca-Vol and NCC Ca-Vol were significant predictors for PVL after TAVI. Ca-Vol can be measured routinely with preoperative CT and might be useful in predicting PVL.
Abstract 10755: Association Between Weight Loss and Prognosis in Patients With Atrial Fibrillation: The Fushimi AF Registry
Authors: Iguchi Moritake , Hamatani Yasuhiro , Masunaga Nobutoyo , Ishii Mitsuru , Ide Yuya , Fujino Akiko , Yoshizawa Takashi , DOI KOSUKE , Ikeda Syuhei , Ishigami Kenjiro , Minami Kimihito , Nakanishi Yumiko , Esato Masahiro , Wada Hiromichi , Hasegawa Koji , Ogawa Hisashi , Abe Mitsuru , Akao Masaharu
Published: June 2023

Background:
Weight loss is one of the key factors of frailty, and we previously reported that low body weight (≤50 kg) was associated with higher mortality and morbidity in patients with atrial fibrillation (AF). However, the association of weight loss with prognosis in AF patients is unclear.

Methods:
From the Fushimi AF registry, 2,523 patients with data on changes in body weight at 1 year after enrollment and follow-up data after 1 year were included in the analysis. We defined weight loss as changes in body weight ≤-4.5 kg based on the frailty-defining criteria in the Cardiovascular Health Study.

Results:
At 1 year after enrollment, 273 (10.8%) patients had weight loss. Mean body weight (changes) at 1 year in patients with and without weight loss were 58.8±14.1 (-8.7±5.8) and 60.7±13.1 (0.7±3.4) kg, respectively (P=0.03). Patients with weight loss were more likely to be male, and had more heart failure, diabetes and chronic kidney disease at baseline. Age and prevalence of prior stroke/systemic embolisms (SE) were similar between the groups, but patients with weight loss had higher incidence of heart failure hospitalization (12.5% and 4.7%) and stroke/SE (4.8% and 2.2%) before 1-year follow-up. Landmark analysis after 1 year revealed that patients with weight loss showed significantly higher incidence of all-cause death and cardiac death (Figure A), but not stroke/SE or major bleeding. Incidence of heart failure hospitalization tended to be higher in patients with weight loss, but not statistically significant. Patients with weight loss also showed higher all-cause and cardiac mortality even in those without low body weight (Figure B). After adjustment for clinical confounders, weight loss was significantly associated with the incidence of all-cause death (hazard ratio, 1.79; 95% confidence interval, 1.43-2.21).

Conclusion:
In AF patients, weight loss was significantly and independently associated with higher all-cause mortality.
Abstract 10757: Machine-Learning Models Based on Real-World Data to Predict Rehospitalization or Death After Acute Myocardial Infarction
Authors: Seegan George , O’Kelly James , Kalich Bethany , Shahabi Ahva
Published: June 2023

Introduction:
Prospectively identifying patient characteristics associated with myocardial infarction (MI) readmission would help target patients at high risk of recurrent events for improved clinical management. This study aimed to build and evaluate machine learning models based solely on real world data to identify predictors of rehospitalization or death within one year following acute MI.

Methods:
The study population consisted of adult patients who experienced a first hospitalization for MI between January 1, 2013 and December 31, 2017 in the Optum® Clinformatics® Data Mart, an administrative health claims database from a large US national managed care company. Logistic Regression (LR), Extreme Gradient Boosting (XGBoost), and Deep Neural Network (DNN) models were developed and tested. Model variables included patient demographics, clinical characteristics, and specific treatments. Variable importance for model prediction was ranked.

Results:
Among 96,244 patients who had an initial MI, 15,925 (16.5%) had rehospitalization/death within a year. The LR, XGBoost, and DNN models performed similarly (area under the curve 0.762, 0.774, and 0.785 respectively). The XGBoost was selected as the primary model to assess the relative importance of the variables in predicting MI rehospitalization/death. Of the most impactful variables, older age, higher Charlson Comorbidity Index, presence of chronic kidney disease (all stages), previous heart failure, and no previous coronary arterial bypass graft were highly predictive of MI rehospitalization/death (Figure).

Conclusions:
The machine learning models developed in this study can be implemented within clinical systems to identify patients at high risk for MI readmission to improve care and decision-making. However, these models require external validation in other datasets. Furthermore, performance of the models might be improved by including information such as LDL-C levels and PCSK9 inhibitor use.
Abstract 10779: Lower Socioeconomic Status, Psychological Distress, and Hypertension: A Longitudinal Moderated Mediation Analysis
Authors: Zhang LiYing , Dailey Rhonda , Brook Robert D , Opara Ijeoma N , Liu Xianchen , Carbone Jason T , Levy Phillip
Published: June 2023

Introduction:
Lower socioeconomic status (SES) has been associated with hypertension (HTN); however, the mediators and moderators of this association remain understudied. We used longitudinal data to examine the mediating effect of psychological distress on the link between lower SES and HTN, as well as the racial and sex moderation effects.

Methods:
This study was a secondary analysis of data collected from 2009 to 2019 among adults with six-wave biennial surveys from the Panel Study of Income Dynamics (PSID). SES was assessed with individuals’ education, employment status, and income. The Kessler K6 scale was used to assess psychological distress. HTN was a self-reported physician-diagnose. Data of families’ head who did not have HTN in 2009 were analyzed. Sequential mediation and moderated mediation models were performed using the PROCESS macro in SPSS.

Results:
The mean age of the sample in 2009 was 45 years (33% female). The prevalence of HTN increased significantly from 31% in 2009 to 41% in 2019. Participants who had no HTN with lower SES in 2009 were more likely to develop HTN in 2019 (OR=1.11, 95% CI: 1.03-1.20,
p
<0.01). Sequential mediation analysis showed that psychological distress was a significant mediator of the association between lower SES and HTN (indirect effect=0.02,
p
<0.05) and the mediation effect was moderated by sex but not by race. Females with lower SES were at a higher risk (index of moderated mediation=0.01,
p
<0.05).

Conclusions:
Lower SES was longitudinally associated with increased risk of HTN 10 years later. The link of lower SES and HTN was mediated by psychological distress and sex moderated the mediation effect. Sex-tailored interventions of psychological distress should be considered to reduce risk of HTN in lower SES individuals.
Abstract 10787: Carotid Artery Stiffness Mechanisms Associated With End Organ Damage and All-Cause Mortality: The Multi-Ethnic Study of Atherosclerosis (mesa)
Authors: Pewowaruk Ryan , Korcarz Claudia E , De Boer Ian H , Kestenbaum Bryan , Heckbert Susan R , Tedla Yacob , Gepner Adam
Published: June 2023

Introduction:
Stiff arteries increase the risk of end organ damage to the brain and kidneys. Arterial stiffness can be separated into two main mechanisms: 1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to remodeling of the vessel wall. The relationship between arterial stiffness mechanisms and end organ damage risk is unknown.

Hypothesis:
Both stiffness mechanisms will be significantly associated with chronic kidney disease (CKD), dementia, and mortality.

Methods:
MESA participants with B-mode carotid ultrasound in 2000-2002 were included in this study (n=6147). Carotid pulse wave velocity (cPWV) was calculated to represent total stiffness. Structural stiffness was calculated by adjusting cPWV to a 120/80 BP with participant-specific models. Load dependent (LD) stiffness was the difference of total and structural stiffness. Associations with incident CKD, dementia defined by ICD codes, and mortality were assessed with Cox models adjusted for age, sex, race/ethnicity, education, study site, smoking, pack-years, diabetes, BMI, SBP, non-HDL-C, BP medication, and lipid medication.

Results:
During 14.3±4.8 years of follow-up, 773 CKD events, 535 dementia events, and 1529 deaths occurred. Total cPWV was associated with mortality (HR 1.04 [1.01-1.08], p=0.02) and dementia (HR 1.06 [1.01 - 1.12], p=0.03). Structural cPWV was significantly associated with mortality (HR 1.04 [1.00 - 1.08], p=0.04) but not CKD (HR 1.00 [0.94-1.05], p=0.86) or dementia (HR 1.06 [0.99-1.13], p=0.06). LD cPWV was associated with CKD (HR 1.38 [1.17 - 1.63], p<0.001) but not mortality (HR 1.11 [0.99-1.25], p=0.07) or dementia (HR 1.14 [0.94-1.38], p=0.19).

Conclusions:
Structural carotid artery stiffness was significantly associated with all-cause mortality, while LD stiffness was significantly associated with CKD. Total carotid stiffness was associated with incident dementia but LD and structural stiffness mechanisms were not.
Abstract 10845: Akt-Dependent Vacuolar Protein Sorting 34 Activation Promotes Pulmonary Vascular Smooth Muscle Cell Proliferation and Survival in Pulmonary Hypertension
Authors: Shen Yuanjun , Goncharov Dmitry , Jiang Lifeng , Lin Derek , Avolio Theodore , Okorie Evelyn , Mora Ana L , Saiyed Aisha
Published: June 2023

Introduction:
Pulmonary arterial hypertension (PAH), a deadly disease with no cure, manifests by small PA remodeling, leading to increased PA pressure and right ventricular (RV) afterload, heart failure, and death. Pulmonary vascular remodeling is characterized by increased proliferation and survival of resident PA vascular cells, the mechanisms of which are not fully understood. Class III phosphatidylinositol 3-kinase vacuolar protein sorting 34 (Vps34) promotes cell hyper-proliferation in cancer. The status and mechanisms of regulation and function of Vps34 in PA vascular cells in PAH are not clear.

Methods/Results:
Immunohistochemical analysis showed that inhibitory Ser164 phosphorylation of Vps34 (P-Ser164-Vps34) was significantly decreased in smooth muscle alpha-actin (SMA)-positive areas of small remodeled PAs from PAH patients compared to PAs from non-diseased donors. Immunoblot (IB) analysis of human PA vascular smooth muscle cells (PAVSMC) from small PAs further demonstrated that P-Ser164-Vps34 is significantly decreased in human PAH PAVSMC. Similar to human PAH, we detected a significant decrease of P-Ser164-Vps34 in SMA-positive areas of small remodeled PAs from mice and rats with SU5416/hypoxia-induced PH, which was associated with increased PA medial thickness, RV pressure, and RV hypertrophy. IB analysis of PAH PAVSMC with Akt inhibitor VIII treatment or Akt-knockdown by specific siRNA demonstrated that Vps34 activation is Akt-dependent, which is associated with TSC2 deficiency, Vps15 over-accumulation, and increased proliferation and survival. Pharmacological inhibition of Vps34 in PAH PAVSMC by selective inhibitors SAR405 and VPS34-IN1 significantly decreased proliferation (Ki67) and induced apoptosis (TUNEL). Two-week treatment of SAR405 in mice with SU5416/hypoxia-induced PH attenuated pulmonary vascular remodeling. The above results suggest a therapeutic potential of Vps34 inhibition to reduce PAH PAVSMC hyper-proliferation and attenuate pulmonary vascular remodeling in PAH.

Conclusions:
Akt-dependent Vps34 activation supports proliferation and survival of PAH PAVSMC. Further studies are needed to evaluate the therapeutic potential of Vps34 inhibition against PAH.
Abstract 10852: Stable versus Dynamic Cardiac Symptom Characteristics Are Associated With Adverse Outcomes Among Individuals Transported by Ambulance for Suspected Acute Coronary Syndrome
Authors: Zegre-Hemsey Jessica K , Crandell Jamie , Rosamond Wayne D , Wong Eugenia , Chronowski Kevin , Tolentino Alec , Ronn Kyle , Steege Noah , Pelter Michele M , Al-Zaiti Salah S , Frisch Stephanie , Dickson Victoria V , Devon Holli A
Published: June 2023

Introduction:
Acute coronary syndrome (ACS) is a potential life-threatening emergency; therefore, rapid diagnosis and life-saving reperfusion therapies are essential to prevent adverse outcomes. Patients with suspected ACS experience an array of symptoms, which cause patients to seek care (9-1-1 or self-transport) to the emergency department [ED]). Little is known, however, about the prognostic value of symptom characteristics experienced in the very early period of evolving ACS and its impact on adverse patient outcomes. The purpose of this study was to determine if early symptom changes reported in the prehospital period are associated with adverse outcomes.

Methods
Adults
>
21 years of age with non-traumatic chest pain and/or anginal equivalent symptoms transported by ambulance were included. Cardiac symptoms were measured prospectively with the ACS Symptom Checklist, a validated 13-item tool that takes approximately one-minute to complete. Trained EMS personnel administered the ACS Symptom Checklist during ambulance transport (T1) and research specialists measured symptoms again in the ED (T2), after acute triage care was completed. Symptom changes were categorized as an increase, decrease, or both from T1 to T2. Changes in symptoms between T1 and T2 were defined as stable (0-3 symptoms) or dynamic (
>
4 symptoms). Adverse hospital outcomes included death, reinfarction, and/or new onset heart failure.

Results
To date, a total of 280 patients presenting to the ED by ambulance with suspected ACS have been enrolled (mean age 60.1
+
15.5 years; 51.2% female; 14.3% final diagnosis of ACS). Of 255(91.1%) patients with complete data, 143(51.1%) experienced stable symptoms and 112(40%) experienced dynamic symptoms. Patients with stable changes had significantly higher rates of adverse outcomes compared to patients with dynamic changes (11.9 versus 2.9%, p=0.007). Patients reporting shortness of breath at T1 or T2 were over 4 times likely to experience an adverse event (p=0.003, p=0007).

Conclusions
Patients with suspected ACS who have stable symptom changes were more likely to have an adverse hospital outcome. The underlying mechanism of plaque rupture in ACS may account for these differences in symptom characteristics but needs further study.
Abstract 10858: Mesenchymal Stromal Cell Delivery via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Surgical Model
Authors: Kobayashi Kei , Sarkislali Kamil , Saric Nemanja , Maeda Takuya , Somaa Fahad A , Bansal Ankush , Tu Shao Ching , Ayodeji Mobolanle A , Leonetti Camille , Hsu Chao-hsiung , Li Jingang , Vyas Pranav , Imamura Kawasawa Yuka , Tu Tsang-Wei , Wang Paul C , Hanley Patrick J , Hashimoto-Torii Kazue , frank joseph A , Jonas Richard , Ishibashi Nobuyuki
Published: June 2023

Background:
Neurodevelopmental impairment is one the most important challenges in children with congenital heart disease. Cardiopulmonary bypass (CPB) causes substantial oxidative/inflammatory stress and microglial activation. The present study tested CPB itself as a unique delivery system of bone marrow-derived mesenchymal stromal cells (BM-MSCs), known to possess significant immunomodulatory properties.

Methods:
Two-week old piglets were randomly assigned to one of three groups: Control, CPB, and CPB with BM-MSC administration. BM-MSCs (10x10
6
/kg) were delivered through CPB. In addition to cellular/molecular assays, structural and behavioral changes were assessed up to 4 weeks after surgery.

Results:
Intra-arterial delivery through CPB uniformly distributed BM-MSCs to most of the organs analyzed, including the brain, heart and kidney. In the brain, BM-MSCs were equally distributed between two hemispheres and within the cortex and white matter. While approximately half of the BM-MSCs were localized to parenchyma shortly after CPB, there were no residual MSCs at 4 weeks post-CPB. In the developing cortex, enhanced p53 and JAK-STAT3 pathway activation were revealed post-CPB. BM-MSCs suppressed CPB-induced microglial STAT3 phosphorylation, thereby inhibiting microglial activation. In addition to an increase in anti-inflammatory cytokines, BM-MSCs reduced caspase-3 activation in cortical neurons and limited the induction of apoptotic signals. BM-MSC-treated animals demonstrated improved post-operative recovery and reduced behavioral impairments due to cardiac surgery. Concurrently, CPB-induced structural alterations of the developing cortex were mitigated possibly through the inhibition of prolonged microglia activation by BM-MSCs. No evidence of any detrimental effects was observed. Our transcriptomic analyses suggest that BM-MSC exosome-derived micro-RNA, miR-21-5p, may be the key mediator of apoptosis suppression and reduced microglial activation.

Conclusions:
BM-MSC delivery via CPB minimizes inflammatory/oxidative stress and reduces neuronal caspase and microglial activation, with subsequent rescue of behavioral/structural impairments in children undergoing cardiac surgery.
Abstract 10863: Left Ventricular Apical Injury Augments Stroke Likelihood in Patients With Systolic Dysfunction and No Left Ventricular Thrombus - Multiparametric Tissue Characterization and Strain Assessment via Cardiac Magnetic Resonance
Authors: Kagan Ruth , Villar Pablo , Tak Katherine , Jain Raina , Rivadeneira Maria , Agoglia Hannah , Kim Jiwon , Okin Peter M , Devereux Richard B , Segal Alan Z , Merkler Alexander E , Kamel Hooman , Weinsaft Jonathan W
Published: June 2023

Introduction:
Patients (pts) with left ventricular (LV) dysfunction are at increased stroke risk even in absence of LV thrombus (LVT), but conventional indices such as ejection fraction (LVEF) have limited predictive value. Cardiac MRI (CMR) enables precise assessment of LV function and infarction, providing utility to test novel markers for stroke risk.

Methods
The population comprised pts with LVEF <50% and no LVT on CMR. Stroke was determined by blinded chart review. LV infarction, LVEF, LV and LA geometry, and segmental wall motion were measured on CMR. To further test association of LV contractility with events, radial strain was quantified in LVEF matched (1:1) pts with and without CVA; segmental data were regionally partitioned (base, mid, apex).

Results
556 pts were studied; 7% (n=40) had stroke. Pts with stroke were older (68±14 vs 60±15 yo) and more likely to have AF (33 vs 18%) or CAD (55 vs 35%; all p<0.05) but did not differ based on CV risk factors (p=NS). Despite similar LVEF (37±8 vs 38±9%) and LV, LA size (p=NS), stroke pts had higher apical wall motion score (8.5±4.4 vs 6.6±3.6) and infarct size (5.3±6 vs 2.4±4.4%; each p<0.01) - each associated with stroke (p<0.001) independent of infarct or dysfunction in non-apical regions. Both apical wall motion (B=1.12 [1.02-1.22]; p=0.013) and infarct (B=1.10 [1.03-1.17]; p=0.006) associated with stroke controlling for age, clinical AF and CAD (
Table
). Among LVEF matched pts, radial strain tended to be higher in the basal LV (192.0±77.7 vs 165.5±56.1; p=0.09) and equivalent in the mid LV (177.8±63.3 vs 175.1±67.2; p=0.85), but apical radial strain was 30% lower (79.2±42.8 vs 109.1±62.4; p=0.015) in pts with, vs. those without stroke.

Conclusion
Among pts with LV dysfunction and no LVT, apical injury augments likelihood of stroke. Parallel associations of LV apical strain quantification, wall motion, and infarction with events support apical injury as risk factor for embolic events even in absence of LVT at time of imaging.
Abstract 10869: Late Pericardial Effusion After Resolution of Takotsubo Cardiomyopathy in Covid-19 Infection. A Rare but Life-threatening Complication
Authors: Ghanta SaiNikhila , Amerneni Krishna Chaitanya , Kumar Dilpat , Vallurupalli Srikanth
Published: June 2023

Background:
Various cardiac complications such as cardiomyopathy and sudden cardiac death have been associated with Coronavirus disease 2019 (COVID-19) pandemic. We present a case of late pericardial effusion after resolution of takotsubo cardiomyopathy in COVID-19.

Case Report:
A 46-year-old male presented with acute hypoxic respiratory failure secondary to COVID-19 pneumonia. His left ventricular ejection fraction (LVEF) was 55% at admission. Over the next two days, his condition worsened requiring mechanical ventilation and inotropic support. A repeat echocardiogram revealed severe biventricular systolic dysfunction with basal hypercontractility and a drop in LVEF to 25%. Cardiac catheterization showed clean coronaries, elevated filling pressures, and reduced cardiac index (CI:1.44L/min/m
2
); hence cardiogenic shock secondary to viral myocarditis/takotsubo cardiomyopathy was suspected and an impella was placed. His condition improved with high-dose steroids, diuretics, and heart failure medication. He was subsequently weaned off circulatory and inotropic support and LVEF improved to 60% in four days, hence a provisional diagnosis of takotsubo cardiomyopathy was made. However, three days post-Impella removal he became tachycardic and hypotensive and a repeat echocardiogram showed moderate pericardial effusion with purulent material and Right Ventricle (RV) free wall diastolic collapse(image). He underwent emergent pericardiocentesis draining 800 ml of purulent fluid with pericardial drain placement. Pericardial fluid cultures returned negative. Thereafter, his condition significantly improved and he was discharged on hospital day 15.

Conclusion:
Symptomatic pericardial effusion can occur late in the clinical course even after other cardio-pulmonary symptoms have improved. This case highlights the importance of clinician awareness of the various cardiac complications in COVID-19 and their timely diagnosis and management.
Abstract 10871: Income in Relation to Anxiety and Patient Engagement Among Stroke Survivors Using Smartwatches for Atrial Fibrillation Monitoring
Authors: Naeem Syed , Tran Khanh-van T , Mehawej Jordy , Paul Tenes , Filippaios Andreas , Ding Eric , Mensah Otabil Edith , Noorishirazi Kamran , Wang Ziyue , Lessard Darleen , Howard-Wilson Sakeina , Soni Apurv , Saczynski Jane , McManus David D
Published: June 2023

Background:
Smartwatches are FDA-approved to detect atrial fibrillation (AF). We examined the associations between income level with anxiety, patient activation, and daily wear time in stroke survivors using smartwatches for AF detection.

Methods:
We analyzed data from the Pulsewatch study, a randomized controlled trial (NCT03761394) that enrolled participants aged ≥50 years with a history of stroke or transient ischemic attack, a CHA
2
DS
2
VASc risk score ≥ 2, and no contraindication to anticoagulation. Participants in the intervention group wore a cardiac patch monitor in addition to a smartwatch and smartphone for AF detection, whereas participants in the control group wore only the cardiac patch monitor. At baseline, 14 days, and 44 days, participants completed General Anxiety Disorder-7 and the Consumer Health Activation Index, which examined anxiety and patient activation, respectively
.
Adherence to the Pulsewatch system was measured by watch wear time. A longitudinal linear regression model was used to examine associations between baseline income (earning <$50K/yr. vs.≥$50K/yr.) and changes in anxiety, patient activation, and wear time over the study period.

Results:
A total of 95 participants were included in this study. Participants earning <$50K/yr. were 54.5% male and 90.9% white, while participants earning ≥$50K/yr. were 59.7% male and 88.7% white. At baseline, history of renal disease (12.1% vs 1.6%, 0.029), statin use (84.9% vs 96.8%, 0.034), depressive symptoms (65.6% vs 35.5%, 0.004), and anxiety symptoms (54.5% vs 18.3%, <0.001), were different between the income groups. The high-income group was associated with reduced anxiety and greater activation (β -2.60, p-value <0.001; β 7.83, p-value 0.005, respectively) but not significantly associated with wear-time (β 0.20, p-value 0.50) among stroke survivors.

Conclusion:
Stroke survivors with high baseline income had reduced anxiety and greater engagement when randomly assigned to smartwatch use for AF detection. Baseline income may influence stress levels and engagement associated with smartwatch use. Studies are needed to evaluate how the prescription of wearable devices affects mood and activation among older adults from diverse socioeconomic backgrounds.
Abstract 10882: Homozygous Familial Hypercholesterolemia: Luck Meets Opportunity Meets Knowledge
Authors: Young Lisa , Brown Emily , Martin Seth S
Published: June 2023

Introduction:
Homozygous familial hypercholesterolemia (HoFH) is an inherited autosomal co-dominant disorder characterized by severely elevated circulating low-density lipoprotein (LDL). Monoclonal antibodies are now a treatment focus. Inhibition of proprotein convertase subtilisin kexin type 9 (PCSK9) increases the number of LDL receptors. Inhibition of angiopoietin-like 3 (ANGPTL3) inhibitor is associated with hypolipidemia and reduced risk of cardiovascular disease. We present the case of one of the oldest living patients with HoFH.

Case Description:
The patient is a 67-year-old black woman diagnosed with corneal arcus senilis and xanthomas at the age of 11, with total cholesterol (TC) levels >1000 mg/dL. At age 12, she underwent a partial ileal bypass (PIB) that lowered her TC by 39%. At age 32, she began statin therapy (Lovastatin, intensified to Atorvastatin at age 43). Despite concomitant dietary changes, her LDL levels remained elevated (>400 mg/dL). At age 34, multivessel coronary artery disease was detected and she initiated lipoprotein apheresis. Her LDL-C was reasonably well-controlled over the 20 years on LDL apheresis and high intensity statin therapy. Combined therapy with PCSK9 inhibitors (Evolocumab at age 61, replaced by Alirocumab at age 67) and ANGPTL3 inhibitor Evinacumab (age 67) lowered her LDL-C significantly. Genetic analysis confirmed two LDLR mutations: c.1846-1G>A and c.907C>T.

Conclusion:
Elevated cholesterol levels are linked to a higher risk of premature myocardial infarction and stroke. We report a case of HoFH with successful lowering of LDL levels on dual antibody and high intensity statin therapy along with PIB. Unlike PCSK9 inhibitors, ANGPTL3 inhibitors work independently of LDLRs by stimulating lipoprotein & endothelial lipase. This case offers insight into early surgical and combination drug therapy in HoFH and describes one of the longest living patients with HoFH illustrating treatment evolution.
Abstract 10905: Relationship of Eicosapentaenoic Acid and Docosahexaenoic Acid Dosage to Plaque Progression in Patients With Coronary Atherosclerosis Receiving Statin and Polyunsaturated Fatty Acid Therapy
Authors: Sheppard John P , Lakshmanan Suvasini , Roy Sion K , Bhatt Deepak L , Budoff Matthew J , Nelson John R
Published: June 2023

Introduction:
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 polyunsaturated fatty acids (PUFAs) extensively studied in atherosclerosis. Clinical endpoint and imaging studies have yielded convergent findings favoring pure EPA over mixed EPA/DHA formulations. The effects of EPA and DHA dose on coronary plaque dynamics, however, remain unknown, and could yield insights into the utility of these PUFAs in coronary artery disease.

Methods:
We considered longitudinal studies that compared coronary plaque change in patients receiving statin versus statin+PUFA therapy. Outcomes were % change in total and lipid plaque volume. Treatment effects were calculated as standardized mean difference (SMD), the mean % plaque volume change between statin and statin+PUFA cohorts divided by their pooled standard error. To isolate effects of EPA or DHA dose respectively, treatment arms were pooled by dosage of the PUFA of interest. To account for dependent samples, we fit hierarchical mixed effects models using robust variance estimation, assuming a correlation of 0.5 among treatment effects within multi-arm studies.

Results:
Among 555 screened articles, 11 studies met inclusion criteria. Among 1,070 patients, there were 14 treatment arms stratified by EPA dose, and 15 treatment arms stratified by DHA dose. Meta-regression revealed that EPA dose (g/day) correlated positively with treatment effect (β = 0.3 [0.1, 0.6], P = 0.02), while daily DHA dose correlated negatively with treatment effect (β = -0.4 [-0.7, -0.1], P = 0.01). We found no associations between EPA (β = 0.1 [-0.2, 0.4], P = 0.44) or DHA (β = -0.1 [-0.3, 0.2], P = 0.59) dose and treatment effects for lipid volume (Figure 1).

Conclusions:
Among cohorts receiving statin+PUFA therapy, we found a dose-dependent benefit of administered EPA on coronary plaque volume; the opposite was true for DHA. This adds to a growing body of evidence suggesting DHA may blunt beneficial effects of EPA in atherosclerosis.
Abstract 10925: A Small Molecule Inhibitor of Sarcomere Contractility Acutely Relieves Prolonged Relaxation in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes With Hypertrophic Cardiomyopathy
Authors: Valtonen Joona , Aalto-Setala Katriina
Published: June 2023

Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac diseases primarily caused by mutations in sarcomeric genes. However, HCM is also associated with mutations in non-sarcomeric proteins and a Finnish founder mutation for HCM in non-sarcomeric protein junctophilin-2 (JPH2) has been identified. MYK-461 is a recently described mechanistically novel small molecule that acts at the sarcomere to specifically inhibit contractility that has been proposed as a treatment for HCM. Here, we use MYK-461 to test whether direct reduction in contractility is sufficient to relieve phenotypic characteristics in human-induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) carrying JPH2 mutation T161K.

Hypothesis:
Currently all HCM patients are treated the same regardless of the underlying genetic defect. Current medication does not prevent or stop the thickening of the heart muscle; only the symptoms and arrhythmias can be controlled with beta-blockers or calcium blockers. MYK-461 decreases adenosine triphosphatase activity of the cardiac myosin heavy chain to reduce contractility, thus modifying the characteristic pathology of HCM.

Methods:
Skin fibroblasts from a Finnish patient with HCM causing
JPH2
p.(Thr161Lys) were reprogrammed into hiPSCs and further differentiated into CMs. As a control line, an isogenic counterpart was generated using the CRISPR/Cas9 genome editing method. We evaluated the effect of MYK-461 treatment to T161K-hiPSC-CMs by their functional characteristics associated with
JPH2
mutation.

Results:
By video microscopy, we identified increased contractility (BPM; 41±6 SEM, n=9) and prolonged diastolic phase (ms; 394.8±29.7 SEM, n=9) in T161K-hiPSC-CMs. Treatment with MYK-461 reduced contractility (BPM; 36±3 SEM, n=10) and relaxation phase (ms; 293.1±33.6 SEM, n=10) in a dose-dependent manner, displaying functional characteristics closer to isogenic-hiPSC-CMs control group.

Conclusions:
In conclusion, the results demonstrate that acute reduction in contractility is sufficient to relieve prolonged relaxation. Further, these studies suggest that T161K-hiPSC-CMs provide adequate
in vitro
platform for modelling the functional effect of MYK-461.
Abstract 10946: Myocardial Inflammatory Activity and Oxidative Stress Immunosuppressive Therapy Are Associated With Prognosis in Patients With Cardiac Sarcoidosis
Authors: Nakashima Yusuke , Kobayashi Shigeki , Ishikawa Maho , Hironori Ishiguchi , Fukuda Masakazu , Suetomi Takeshi , Miyazaki Yousuke , Fujiura Tatsuhiro , Uchinoumi Hitoshi , Mochizuki Mamoru , Okamura Takayuki , Yano Masafumi
Published: June 2023

Background: P
atients with cardiac sarcoidosis (CS) have been shown to be at an increased risk of major adverse cardiovascular events (MACE). Enhancement in myocardial inflammatory activity and oxidative stress is a crucial cause of MACE. Immunosuppressive therapy is recommended for the treatment of active CS. After immunosuppressive therapy, however, there is no predictable markers for prognosis. We hypothesized that the inflammation and oxidative stress in heart were associated with MACE.
Aim:
We identified prognostic markers for MACE in patients with CS after steroid therapy.

Methods:
This prospective cohort study enrolled 103 consecutive patients with CS diagnosed according to the Japanese guideline; Of 103 CS patients, 39 patients underwent 18F-FDG PET/CT 6 months after steroid therapy, and levels of urinary 8-hydroxy-2′-deoxyguanosine (U-8-OHdG) as a marker of oxidative DNA damage, other biomarkers, indices of cardiac function, and renal function were measured. Then they were followed up for a median of 42 months. The primary endpoint was a composite of the first sustained ventricular tachycardia (sVT) /sudden cardiac death (SCD), hospitalization for heart failure, and worsening CS with increased accumulation of FDG in heart and exacerbation of clinical manifestation.

Results:
During the follow-up period, 7 of 30 patients showed sVT/SCD (N= 9), hospitalization (N= 2) and worsening CS (N= 4). A Cox proportional-hazard model showed that U-8-OHdG concentration and SUV max value of FDG-PET were independent predictors of MACE. ROC analysis showed that the cut-off values of U-8-OHdG and SUV max for predicting the MACE were 14.2 ng/mg·Cr and 4.6 respectively. Patients with a U-8-OHdG ≥ 14.2 ng/mg·Cr or SUV max ≥4.6 had a significantly higher MACE risk (Figure A and B).

Conclusions:
U-8-OHdG and SUV max after steroid therapy were powerful predictors of MACE in CS, suggesting that CS patients with high U-8OHdG and/or high SUV max might be resistant to steroid therapy.