bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11218: The Variation of Left Heart Size Based on Donor and Recipient Sex and Its Impact on Outcomes After Orthotopic Heart Transplant
Authors: Kozaily Elie , El Am Edward , Jafri S. Hammad , Trevino Alexandra M , Cummings Emily L , Bou Chaaya Rody G , Sabra Mohamad , Savsani Parth , Tiahnybik Jack , Guglin Maya
Published: June 2023

Introduction:
The impact of sex mismatch on outcomes after orthotopic heart transplant (OHT) remains unclear. We aimed to evaluate the change in left ventricle (LV) size based on donor and recipient sex and examine its association with the outcomes.

Methods:
This was a single institution, retrospective study among OHT recipients between Jan 2015 and Sept 2020. Patients were excluded if they were<18 years old, received OHT for congenital heart disease, had follow-up<6 months or missing donor variables. We collected donor (D) and recipient (R) clinical and echocardiographic characteristics. First and last echo post OHT were collected at least 2 months apart. Donor data was extracted from UNOS database. Primary outcome was the variation in donor heart size based on sex at first and last echo after transplant and the difference in survival or HF hospitalization. Statistical analysis (T test) was performed using Stata 15.1.

Results:
Among 156 reviewed patients, N=68 were included. Female (F) recipients (R) median age was 51±16 y, 25% were African-American (AA) while male (M) recipients median age was 56±12y and 19% were AA. Pre-transplant, MR had a higher RV and LV predicted heart mass and higher CO, CI by Fick. Aside from a higher prevalence of hypertension in MR, there was no difference in baseline characteristics. OHT allocation was MD/MR (66%); FD/FR (18%); FD/MR (4%); MD/FR (12%). LVEDD was bigger in MR on the first echo and remained on last echo post-transplant. There was no difference in degree of variation of LV parameters (LVEDD, LVESD, LV thickness) in MD/MR vs FD/MR and FD/FR vs MD/FR. Compared to sex matched, sex mismatched cohort had a non-significant trend towards a bigger degree of variation in LV size at first (-9% ± 10% vs -2% ± 21%;p=0.14) and last echo (-8% ± 12% vs -4% ± 14%;p=0.1).There were 18% (66% acute cellular rejection) cases of rejection split in half between sex matched and mismatched cohort. At a follow-up duration up to 6 years, 25% (N=17/68) of patients did not survive. There was no difference in survival or HF hospitalization in MR vs FR, in sex matched vs sex-mismatched.
Conclusions:
This is one of the first studies to examine the change in LV size and its impact on outcomes post OHT. The potential impact of LV behavior in M vs F is worth exploring on larger cohorts.
Abstract 11231: Acetylcholine Receptor Agonists Exert Cardioprotection Against Trastuzumab-Induced Cardiotoxicity by Attenuating NLRP3/GSDMD-Mediated Pyroptosis
Authors: Prathumsap Nanthip , Ongnok Benjamin , Khuanjing Thawatchai , Arinno Apiwan , Maneechote Chayodom , Chunchai Titikorn , Arunsak Busarin , Kerdphoo Sasiwan , Chattipakorn Siriporn , Chattipakorn Nipon
Published: June 2023

Introduction:
The most significant adverse effect of trastuzumab (TRZ) is cardiotoxicity. Multiple factors are involved in the pathogenesis of TRZ-induced cardiotoxicity (TIC), including mitochondrial dysfunction, inflammation, and pyroptosis. Although vagal modulation using acetylcholine receptors (AChR) agonists have been shown to exert cardioprotection in various heart diseases, the effects of AChR agonists against TIC have not been investigated.

Hypothesis:
We hypothesized that AChR agonists exert cardioprotective effects against TIC by attenuating cardiac mitochondrial dysfunction, inflammation, and cardiomyocyte pyroptosis, leading to improved left ventricular (LV) function.

Methods:
Wistar rats were divided into 5 groups, including i) control (0.9%NSS), ii) TRZ+VEH (TRZ, 4 mg/kg+VEH), iii) TRZ+α7 nicotinic AChR agonist (α7nAChR: PNU-282987, 3 mg/kg/day), iv) TRZ+muscarinic AChR agonist (mAChR: bethanechol, 12 mg/kg/day), and v) combined PNU+BET treatment groups (COM). At the end of the experiments, cardiac biochemical and functional analyses were determined.

Results:
TRZ-treated rats showed a decreased %LV ejection fraction (%LVEF) (Fig. 1A). Moreover, mitochondrial reactive oxygen species (ROS) levels and mitochondrial depolarization were increased in TIC rats (Fig. 1B-C). TRZ-treated rats also exhibited the upregulation of
interleukin-6
mRNA, NLR family pyrin domain containing, and cleaved-gasdermin D/gasdermin expression (Fig. 1D-F). All AChR agonists similarly protected the hearts by attenuating cardiac mitochondrial dysfunctions, inflammation, and pyroptosis, leading to improved LV function in TIC rats (Fig. 1A-F).

Conclusions:
Either α7nAChR or mAChR agonist equally exerted cardioprotective effects against TIC by reducing cardiac mitochondrial dysfunction, inflammation, and pyroptosis, culminating in improved LV function. These findings provide potential novel treatment strategies against TIC.
Abstract 11274: VERVE-101—An Investigational Single-Course Gene Editing Medicine Targeting PCSK9—Durably and Potently Lowers PCSK9 and LDL-C Concentrations in Non-Human Primates
Authors: Lee Richard , Mazzola Anne M , Braun Maurine , Platt Colin , Vafai Scott , Kathiresan Sekar , rohde ellen , Bellinger Andrew M , Khera Amit V
Published: June 2023

Introduction:
VERVE-101 is an
in vivo
CRISPR base editing therapy designed to alter a single DNA base in the
PCSK9
gene, permanently inactivate hepatic expression, and thereby durably lower LDL cholesterol (LDL-C). Here, we test the efficacy, tolerability, and potential for germline editing of VERVE-101 in studies of 43 non-human primates.

Methods:
Cynomolgus monkeys were dosed with a single intravenous infusion of a vehicle control (N = 10) or VERVE-101 at a dose of 0.75 mg/kg (N = 4) or 1.5 mg/kg (N = 22) with subsequent assessment of liver
PCSK9
editing, reductions in blood PCSK9 and LDL-C, and safety parameters. A second study evaluated sexually mature male non-human primates dosed with a vehicle control (N = 1) or 1.5 mg/kg of VERVE-101 (N=6) to assess for any germline cell editing.

Results:
Liver biopsies 14 days after dosing noted mean
PCSK9
editing of 46% and 70% in monkeys treated with VERVE-101 at 0.75 and 1.5 mg/kg respectively. This translated into reductions in blood PCSK9 of 69% and 89% and reductions of LDL-C of 50% and 68% at the 0.75 and 1.5 mg/kg doses, respectively, measured one year after dosing (
Figure).
Liver safety monitoring noted a transient rise in ALT and AST concentrations following infusion that fully resolved by day 14 with no accompanying change in total bilirubin. VERVE-101 did not impact glucose homeostasis, as assessed by serial monitoring of fasting glucose and hemoglobin A1c. In the study to assess germline editing, VERVE-101 was similarly well tolerated and no editing of
PCSK9
was observed in sperm samples obtained 90 days after dosing.

Conclusions:
A single intravenous infusion of VERVE-101 in non-human primates was well-tolerated and led to 89% lower blood PCSK9 protein and 68% lower blood LDL-C at one year after dosing. These results support initiation of a first-in-human clinical trial in patients with heterozygous familial hypercholesterolemia and atherosclerotic cardiovascular disease, with initial patient dosing anticipated in mid-2022.
Abstract 11285: Synthetic-Contrast-Enhanced Computed Tomography Creating by Machine Learning Without Contrast Media
Authors: Tsujimoto Takanori
Published: June 2023

Introduction:
Contrast-enhanced computed tomography (CECT) is the gold standard for the diagnosis of aortic dissection (AD), at the same time, CECT has risks of nephropathy and allergic reactions caused by contrast media.

Hypothesis:
Synthetic-contrast-enhanced computed tomography (SECT) created from non-contrast-enhanced computed tomography (NECT) by machine learning without contrast agents could be an alternative to CECT in the diagnosis of AD.

Methods:
50 patients with type A AD and 200 patients without AD who underwent NECT and CECT in pairs at Kobe university hospital were randomly selected and used for model training and testing. 3120 CT slices were used for training and 379 slices were used for testing. AD detection algorithms for NECT or CECT were developed by convolutional neural networks using NECT datasets or CECT datasets respectively. A SECT creating algorithm was developed by u-net using the pairs of CT datasets. To provide visual explanations of diagnosis, the gradient-weighted class activation mapping (Grad-CAM) method was adapted.

Results:
The provided sensitivities of AD detection algorithms for NECT or SECT were 90 % and 97 %, and the specificities were 100 % and 100 % respectively. When the developed AD detection algorithms for CECT were adapted to SECT, the provided sensitivity of 100 %, and sensitivity of 95 %. Most slices SECT of patients with AD demonstrated intimal flap and/or thrombosed false lumen as the almost same as CECT. The Grad-CAM visualization revealed that the AD detection algorithm using SECT images identified intimal flap or thrombosed false lumen in images more clearly than the AD detection algorithm using NECT images.

Conclusions:
The SECT creating algorithm improved diagnostic sensitivity for detecting AD using NECT datasets, which suggests the potential of the proposed method to support the clinical practice by reducing complications of contrast agents.
Abstract 11302: Natural Heart Regeneration After Myocardial Infarction in Newborn Rats Provides Ultra-Long-Term Protection From Cardiac Dysfunction and Mortality
Authors: Wang Hanjay , Shin Hye Sook , Mullis Danielle , Tran Nicholas , Jung Jinsuh , Wu Matthew , Elde Stefan , Zhu Yuanjia , Woo Y. Joseph J
Published: June 2023

Introduction:
Newborn rats exhibit natural heart regeneration after myocardial infarction (MI), yielding no evidence of cardiac dysfunction or scar at 3 weeks post-MI. This phenotype is absent when MI occurs after 1 week of age. The long-term function of the regenerated heart and its impact on survival post-MI have not been studied. We hypothesized that natural heart regeneration preserves cardiac function and normalizes survival through adulthood.

Methods:
Wistar rat neonates (n=51) underwent left anterior descending coronary artery ligation on postnatal day 1 (P1, n=17) or postnatal day 9 (P9, n=12). Sham surgery was performed in littermates (P1 n=12, P9 n=10). The rats were observed for the entirety of their lifespan, reaching 18 months post-MI (equivalent to 45 human years) at the time of this analysis. Echocardiography was obtained at 15 months post-MI. After each mortality event, hearts were sectioned and stained with Masson’s trichome.

Results:
Echocardiography at 15 months after P1 MI vs P1 sham surgery revealed no differences in left ventricular (LV) wall thickness (p=0.881, Fig 1A) or end-diastolic diameter (p=0.118, Fig 1B), and LV ejection fraction (EF) was sustained within normal limits (63.2% vs 68.5%, p=0.003, Fig 1C). In contrast, after P9 MI, severe LV wall thinning (p<0.001), massive LV dilation (p<0.001), and profoundly depressed EF were observed (41.8% vs 69.1%, p<0.001). Concordant results were observed for both sexes. Trace scar was detected after P1 MI, while large infarcts and LV aneurysms were observed after P9 MI (Fig 1D). At 18 months post-MI, overall survival was 13/17 (76.5%) in the P1 MI group compared to 9/12 (75.0%) in the P1 sham group (p>0.999) and 3/12 (25.0%) in the P9 MI group (p=0.009).

Conclusions:
Natural heart regeneration mechanisms may offer long-term protection from LV dysfunction and mortality after cardiac injury, suggesting potential applications in congenital heart surgery and as a durable treatment for ischemic cardiomyopathy.
Abstract 11318: A Rare Case of Stretch Syncope of Adolescence Masquerading as Carotid Artery Dissection and Carotid Sinus Syndrome
Authors: Mital Rahul , Henry Kelly
Published: June 2023

Introduction:
Syncope describes a brief, sudden loss of consciousness and tone, with spontaneous return to baseline. Although episodes arise from a transient interruption of cerebral blood flow, work-up identifying an underlying is critical, as it can determine the proper treatment for cessation of these episodes. In this case, we describe a patient who was later diagnosed with stretch syncope of adolescence (SSA), a rarely reported cause of syncope.

Case Presentation
A 16-year-old male presented to the E.R. after experiencing a syncopal event immediately after looking up. He endorsed a similar episode one week earlier, after standing and looking up. The patient also revealed that he commonly would crack his neck and would often sleep with his head extended over the arm of his couch.

In the E.R., the patient was hypotensive to 107/62 mmHg, but physical exam and lab work-up did not reveal any significant pathology. EKG and a CT head without IV Contrast showed no acute intracranial abnormality.

Soon after admission, he became bradycardic, hypotensive, and lightheaded. Due to concern for carotid artery dissection, bilateral carotid duplex scan and CT of the head and neck were completed, and given the reproducibility of the patient’s symptoms with neck dorsiflexion, an MRI to evaluate for carotid sinus syndrome was completed. All imaging, however, returned unremarkable. Given the patient’s age, symptom onset with movement, and exclusion of other etiologies, a diagnosis of SSA was made. The patient was discharged with strict instructions to avoid stretching, especially when standing.

Discussion
SSA is characterized by episodic loss of consciousness triggered by a combination of stretching and neck hyperextension. It is a rarely reported phenomenon, with only 14 case reports published on SSA as of 2014, and is often confused with more common syndromes, most commonly epileptic seizures. Our case is especially unique because the patient’s presentation was initially most consistent with carotid artery dissection and coronary sinus syndrome, a previously unreported presentation. By continuing to recognize and report cases such as ours, patients with SSA may receive more prompt diagnosis, avoid extraneous work-up, and ultimately, prevent future syncopal events.
Abstract 11321: The Characteristic, Procedural Safety and Middle Term Clinical Outcome Study of Chronic Total Occlusion Percutaneous Coronary Intervention Among Elderly Aged <75 Years versus ≥75 Years
Authors: Kim Heng Shee , Imura Shinji , Ando Motosu , Tarutani Yasuhiro , Miwako Tsukiji , Nakanishi Yuuki , Ono Yasuhiro , Fumitaka Hosaka
Published: June 2023

Introduction:
The elderly is frequently related to frailty, comorbidities, and higher short- and long-term complications in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). The data was scarce. Thus, we aim to study the feasibility, safety, and outcome of CTO-PCI among the elderly aged <75 years versus ≥75 years.

Methods:
We performed a consecutive retrospective analysis of 258 CTO-PCI attempted at Okamura Memorial Hospital, Japan, from September 2015 to April 2021 via the electronic health record. It was categorized into <75 years and ≥75 years. All patients were analyzed for demographic, PCI, and follow-up details. We define target lesion failure (TLF) as the composite of cardiac-related death, target-vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (TLR). Regression analysis was done to identify specific risk factors for TLF.

Results:
Among attempted CTO-PCI, 177 (68.6%) <75 years and 81 (31.4%) ≥75 years. There was no significant short-term or in-hospital complication between both groups, except a significantly higher wire or vessel perforation in the elderly (4.0% vs. 12.3%). Left main CTO-PCI was more frequent in the elderly (2.3% vs. 8.8%). The high success rate was no difference between both groups (97.7% vs. 97.5%), with a very high number of IVUS used in both groups (98.9% vs. 100%). The 1-year TLF was insignificant between both groups (10.2% vs. 8.6%). The contrast volume and non-hypertensive patients were found to significantly increase the risk of TLF in the elderly ≥75 Years (OR 1.02 - 17.93).

Conclusion:
Our study demonstrated that CTO-PCI in elderly patients is feasible, safe, and with excellent mid-term TLF outcomes compared with the younger patients. The identified risk factors related to TLF may be able to guide the management strategy in this group of patients. Thus, CTO in the elderly should not be deprived of an invasive PCI strategy when indicated.
Abstract 11338: Stimulant Use Precipitates Antidromic Atrioventricular Reentrant Tachycardia While Subsequent Evaluation Reveals Underlying Ebstein Anomaly
Authors: Dapas Natalie , Nazari Matthew , Thomaides Athanasios , Srichai-Parsia Monvadi
Published: June 2023

Background:
Ebstein anomaly (EA) or congenital atrialization of the right ventricle occurs in 0.005% of the population. Developmental tricuspid valve malformations in EA can establish accessory pathways (APs) in 10-30% of these patients. These APs can lead to atrioventricular reentrant tachycardia (AVRT) with sometimes consequent fatal complications (2.7% if untreated).

Case:
A healthy 23-year-old woman presented with dyspnea and palpitations after cocaine use. Her initial EKG demonstrated wide complex tachycardia with a HR of 200 bpm and BP of 70/40 mmHg. She received electrical cardioversion and amiodarone. Subsequent EKG demonstrated antidromic AVRT versus pathway-pathway tachycardia (
Figure 1A-B
). TTE demonstrated right ventricular atrialization consistent with EA (
Figure 1D-E
). Dual right anterolateral and mid-septal APs were mapped (
Figure 1F
) and ablated.

Conclusion:
Antidromic AVRT is a life-threatening, wide complex tachycardia that can be mistaken for ventricular tachycardia, with the potential for catastrophic outcomes if mismanaged. Demonstrative EKG findings reveal the diagnosis (
Figure 1-2
), while hemodynamic stability guides acute management (
eg
, IV procainamide vs cardioversion,
Figure 2C
), followed by AP ablation for definitive management. Rapid recognition with evaluation for structural disease (herein as EA) is essential to affording optimal management in AVRT.
Abstract 11350: Arrhythmogenic Mitral Valve Prolaspe and Mitral Annular Disjunction
Authors: Shamaki Garba Rimamskep , Markson Favour , Beheshti Sheda Monfared
Published: June 2023

Background:
Mitral valve prolapse (MVP) affects about 2-3% of the general population. A small proportion of persons may have arrhythmic symptoms, leading to ventricular arrhythmias and sudden cardiac death (SCD). Mitral annular disjunction is a recently described entity that may be present with MVP or independently.

Case:
A 55-year-old male patient presented to the hospital with cardiac arrest. He has a history of percutaneous coronary intervention with stenting to left anterior descending (LAD) and right coronary artery (RCA) in 2015. He had ventricular fibrillation (VF) and subsequently arrested and underwent resuscitation. Electrocardiogram (EKG) showed sinus rhythm with prolonged QTc 487msec with no ischemia; echocardiography showed mitral annular disjunction, severe left ventricular global hypokinesis with ejection fraction of 10%. Left heart catheterization revealed nonobstructive moderate coronary artery disease. Right heart catheterization showed a severely reduced cardiac index of 2.1, and he was placed on mechanical support (Impella) for cardiogenic shock. On day 5, repeat echocardiography revealed left ventricular ejection fraction of 60%. Subsequent cardiac magnetic resonance (CMR) showed no evidence of infiltrative diseases but revealed an inferolateral wall scar from previous myocardial infarction and MVP with MAD. An implantable cardiac defibrillator was placed for secondary prevention of SCD.

Discussion:
The potential etiology of our patient's ventricular fibrillation cardiac arrest may include a scar from previous myocardial infarction or arrhythmogenic MVP with MAD. Myocardial fibrosis arising from MAD may be an origin of ectopic activity and arrhythmia. EKG, echocardiographic, and cardiac magnetic resonance imaging (CMR) are essential in diagnosing arrhythmic MVP and MAD. Young patients with premature ventricular contractions without clear etiology should be evaluated for MAD, and incidental findings of MAD should warrant further investigations, given its arrhythmogenic potential.

Conclusion:
MVP with MAD is associated with life-threatening arrhythmias. Further studies are required to explore treatment options to reduce the incidence of malignant VAs and SCDs in patients with MVP.
Abstract 11381: Associations Between Serum and Dietary Omega-3 to Omega-6 Ratio and Cognitive Function in a Population of Community-Dwelling Japanese. -Tanushimaru Study-
Authors: Fukami Ako , Adachi Hisashi , Enomoto Mika , Nohara Yume , Nagisa Morikawa , Sakaue Akiko , Maki Yamamoto , Sato Hiromi , Fukumoto Yoshihiro
Published: June 2023

Introduction:
Previous studies indicate that dietary omega-3 polyunsaturated fatty acids (PUFA) are modifiable risk factors for CVD and cognitive decline. This study aimed to investigate the association between serum and dietary omega-3/omega-6 PUFA ratio and cognitive function were measured in a general population.

Hypothesis:
We assessed the hypothesis that the serum and dietary omega-3/omega-6 PUFA ratio preserve a cognitive function. Method: A total of 976 residents (381 males, 595 females, mean age 62.6 years) underwent a physical examination, a nutrition survey and the mini-mental state examination as an evaluation of cognitive function in 2009 and followed up in 2018.

Results:
The serum omega-3/omega-6 ratio were significantly associated with age (p < 0.0001), sex (male, p <0.0001), MMSE ( p < 0.0001), LDL-c ( inversely, p < 0.01), and salt intake ( p < 0.05), using by multiple stepwise regression analysis. The dietary intake of proteins from fish ( p < 0.0001), trace elements, ( p < 0.01), vitamin D, B6, B12 ( p <0.0001), and salt ( p < 0.0001) showed dose dependent relationships with the serum omega-3/omega-6 ratio using analysis of covariance. Subjects were divided into 4 groups according to their progression of cognitive decline in 10 years. Serum omega-3/omega-6 ratio of group with normal cognitive function (NC) were significantly higher than those of group with cognitive decline (CD) (p < 0.05). However, dietary intakes of omega-3 and omega-6 PUFA were not significant. Interestingly, salt intakes in group with CD were higher than those in group with NC (p < 0.05). The logistic regression analysis revealed that salt intakes was associated with cognitive decline 10 years later after adjustments for confounding factors (odds ratio, 1.1; 95% C.I., 1.01-1.13; p = 0.01) In conclusion, the present study demonstrated that omega-3 PUFA may preserve a cognitive function and excessive intakes of salt may have an adverse effect on cognitive function.
Abstract 11394: The Yield of Stress Myocardial Perfusion Imaging in Patients With Chest Pain and Low Pretest Probability of Coronary Artery Disease
Authors: Aljizeeri Ahmed H , Ahmed Amjad M , Zayed Mohammed , AlaliAlfaris Mousa , Elneama Awadelkarim , Suliman Ihab , Alharthi Mohsen , Alsaileek Ahmed A , Al-Mallah Mouaz
Published: June 2023

Introduction:
Chest pain is a common presentation in the emergency department and physician office visits. Identifying coronary artery disease (CAD) as the cause of chest pain is essential for improving prognosis. The 2021 AHA/ACC guidelines do not advocate for testing in patients with low pretest probability (PTP <15%) of CAD. However, the pretest probability does not account for CAD risk factors. We sought to evaluate the yield of stress myocardial perfusion imaging (MPI) in patients with chest pain and low PTP of CAD in a population with a high prevalence of CAD risk factors.

Methods:
We reviewed all the patients referred to positron emission tomography from May 2011 to January 2022. Patients with chest pain and low PTP of CAD were included in the analysis. Patients with heart failure and valvular heart disease were excluded. Low PTP was defined as ≤15% on Juarez-Orozco classification. Moderate-severe ischemia is defined as ≥10% ischemic myocardium.

Results:
2235 patients (age 54.2 ± 9.3 years, 23.8% males) with low PTP of CAD were included in the analysis. 303 (13.6%) of the cohort had ischemia out of which 100 (33%) patients had moderate-severe ischemia. Patients with ischemia had more prevalence of diabetes, hypertension, and hypercholesterolemia. The presence of two risk factors was associated with a higher likelihood of moderate-severe ischemia (OR = 2.2, 95%CI: 1.1 - 4.4, p=0.025)

Conclusions:
Ischemia is common among patients with low PTP of CAD and a high prevalence of risk factors. The presence of two risk factors is associated with a more than 2-fold increase in the risk of moderate-severe ischemia. Risk factors should be taken into consideration when deciding about further testing in this population. Further studies are needed to verify the prognostic value of testing in this population
Abstract 11401: Silent Brain Infarct on MRI Predicts Clinical Stroke/ Transient Ischemic Attack in Mitral Stenosis
Authors: Naik Nitish , roy ambuj , RAI NITIN , Kumar Kapil , Sharma Meenakshi , kumar sanjeev , Jagia Priya , Ramakrishnan Lakshmy , Yadav Rakesh , Sharma Gautam , Singh Sandeep
Published: June 2023

Introduction:
Mitral stenosis (MS) is associated with a high risk of cardio-embolic events. However, current recommendations for initiating anti-coagulant therapy in patients with MS is limited to patients with atrial fibrillation (AF),atrial thrombi or those with a prior stroke. In patients with moderate to severe MS who are in sinus rhythm there are no firm recommendations for anti-coagulation despite a known higher risk of thromboembolic events. Moreover there is limited data on the prevalence of silent brain infarcts (SBI) in patients with MS. This study evaluated prevalence and predictors of silent and clinical stroke in MS.

Methods:
A total of 211 patients with moderate to severe MS (mitral valve area ≤ 1.5 cm2) were recruited in the study and were followed up over a7 year period. Patients with existing left atrial clot(s) or prior valvular intervention were excluded from the study. All patients underwent clinical examination, ECG, echocardiogram, and brain MRI on a 1.5T machine. A 24-hour Holter was performed on patients in sinus rhythm.

Results:
Among 211 patients, 87(41.2%) were male and 140 (66.3%)were in sinus rhythm. Moderate to severe mitral regurgitation and/or aortic regurgitation was present in 31 (14.7%) and 30 (14.2%)patients respectively. SBI was seen in 44 (20.9 %) patients [26 (18.6%)in sinus rhythm and 18(25.4%) in AF]. Female gender (OR 2.3 95% CI 1.01-5.1, p = 0.043), poorer NYHA functional class (Class II OR 16, 95%CI 4.1-62.8, p=0.001; Class III OR 4.1 95%CI 1.2-13.8, p = 0.024),AF (OR 3.8 95%CI 1.6-8.9 p = 0.002) and aortic regurgitation (OR 3.7 95%CI 1.3-10.4 p = 0.011)were associated with increased risk of SBI. Seventeen patients (8%) were lost to follow up. Among 194patients who completed follow up, clinical stroke/TIA occurred in 15 (7.7%) patients. SBI on MRI was associated with a higher risk of clinical stroke/TIA on follow up on multivariate analysis (OR 3.7 95%CI1.26-10.9, p=0.018).

Conclusions:
Silent brain infarction is present in a significant minority of patients with MS and is predictive of clinical stroke/TIA on follow up.
Abstract 11403: Systemic Administration of High Mobility Group Box 1 Fragment Improves Cardiac Functions via Activating Tissue Healing Pathway of Bone-Marrow Mesenchymal Stem Cell in a Porcine Ischemic Cardiomyopathy Model
Authors: Ito Yoshito , Kawamura Masashi , Kawamura Takuji , Tamai Katsuto , Yoshioka Daisuke , Saito Tetsuya , Matsuura Ryohei , Misumi Yusuke , Harada Akima , Goto Takasumi , Watabe Tadashi , Yamada Atsushi , Taira Masaki , Shimamura Kazuo , Toda Koichi , Miyagawa Shigeru
Published: June 2023

Introduction
:
Regenerative therapy for heart failure (HF) points to bone marrow mesenchymal stem cell (BM-MSC) as a promising cell source. High mobility group box 1 (HMGB1) is a nuclear protein involved in tissue homeostasis. In this study, we developed an HMGB1 fragment containing a BM-MSC mobilization domain.

Hypothesis:
We hypothesize that the HMGB1 fragment improves cardiac function by activating a tissue healing pathway of BM-MSC within a porcine ischemic cardiomyopathy (ICM) model as a pre-clinical study.

Methods:
Gottingen mini pigs weighing 15-25 kg were used. An ICM model was generated by placing an ameroid constrictor ring (internal diameter; 3.5 mm) on the left anterior descending artery (LAD). After 4 weeks, either the HMGB1 fragment (HMGB1 group; 3 mg/kg, n=6) or normal saline (control group; n=5) was administered intravenously with one dose every 48 h for five times. We examined cardiac function before and 8 weeks post treatment through echocardiography, cardiac magnetic resonance imaging (cMRI) with late gadolinium enhancement (LGE), and a fluoroscopy-guided pressure wire study. Then, histological analysis was performed.

Results:
In echocardiography, ejection fraction significantly improved in the HMGB1 group compared with the control (+11.1% vs -4.8%, p=0.0003). cMRI with LGE demonstrated that the areas of damaged myocardium (core infarct zone + border zone) in the LAD region was reduced in the HMGB1 group compared with the control group (-11.9% vs +17.9%, p=0.0090). Coronary flow reserve (CFR) and resistive reserve ratio (RRR) were evaluated through pressure wire study; they improved in the HMGB1 group compared with the control group (ΔCFR; +0.38 vs +0.01, p=0.0249, ΔRRR; +0.42 vs +0.07, p=0.0275). Histological analysis showed that cardiomyocyte size (26.6 μm vs 38.0 μm, p=0.0339) and areas of fibrosis were smaller (9.8% vs 11.6%, p=0.1649), and the density of CD31-positive endothelial cells was higher (1033/mm
2
vs 640/mm
2
, p=0.0339) in the HMGB1 group than in the control group.

Conclusions:
Systemic administration of the HMGB1 fragment improved cardiac function, coronary flow reserve, and reduced cardiac fibrosis in an ICM model. This drug-induced activation of inner tissue repair and regeneration is a novel approach to treat HF.
Abstract 11404: Phenotyping Cardiac Sarcoidosis With PET/MR: Imaging Characteristics, Treatment Response, and Outcomes of Isolated Cardiac Sarcoidosis versus Extra-Cardiac Sarcoidosis With Cardiac Involvement
Authors: Rojulpote Chaitanya , Bhattaru Abhijit , Patil Shivaraj , Vidula Mahesh K , Peyster Eliot G , Frankel David S , Nazarian Saman , Litt Harold I , Goldberg Lee R , Marchlinski Francis E , Bravo Paco E
Published: June 2023

Introduction:
Diagnosing cardiac sarcoidosis (CS) remains challenging due to limitations of available clinical criteria and low yield of endomyocardial biopsy. PET-MR imaging allows for multidimensional non-invasive assessment of suspected CS. However, the true diagnostic and prognostic impact of these modalities require further exploration.

Hypothesis:
PET-MR can phenotype CS and its associated treatment response.

Methods:
We identified 100 patients with known or suspected CS (52±1.8 years, 66% male) who underwent PET-MR imaging: 38 individuals with isolated CS (ICS) (50±1.8 years, 65% male) and 62 subjects with CS and biopsy-proven extra-cardiac sarcoidosis (ECS) (52±2.4 years, 66% male). A subset of 56 patients (24 ICS and 32 ECS) was classified as the phenotype cohort if they were: 1) treatment naïve, 2) started on immunosuppressant treatment after PET, and 3) had follow up PET to assess treatment response, which was graded as complete (CTR), partial (PTR), and no response (NR). PET-MR phenotype was graded as combined imaging findings suggestive of CS (Figure 1A), equivocal for CS, and not suggestive of CS. Major adverse cardiovascular events (MACE) were defined as sustained ventricular tachycardia, ventricular fibrillation, heart transplantation and/or cardiac death at 1 year.

Results:
From the ICS phenotype cohort, PET-MR findings suggestive of CS were present in 100% (8/8) of patients with biopsy-proven ICS vs. 56% (9/16) of subjects without biopsy (P=0.03). CTR/PTR rates were overall higher in ECS compared to ICS (81% vs. 58%; P=0.06), and in patients with PET-MR suggestive of CS (P=0.01; Figure 1B), in both the ECS (P=0.04) and ICS (P=0.08) groups. MACE events were significantly greater in ICS vs ECS (HR 3.9 [1.6 - 9.7]; P=0.003), and in patients with PET-MR suggestive of CS (HR 8.2 [1.1 - 62]; P=0.04; Figure 1C).

Conclusion:
PET-MR can identify phenotypes of CS which have distinct disease manifestations, treatment response rates, and clinical outcomes.
Abstract 11427: Clot Strength and Platelet Reactivity for Prediction of Major Cardiovascular Events After Percutaneous Coronary Intervention
Authors: Kwon Osung , Ahn Jong-Hwa , Koh Jin-sin , Park Yongwhi , Hwang Seok-Jae , Kim Sang-Wook , Hwang Jinyong , Jeong Young-Hoon
Published: June 2023

Introduction:
Platelet-fibrin clot strength (PFCS) is associated with the risk of major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD).

Hypothesis:
The interaction between PFCS and platelet reactivity, and their prognostic implication remain uncertain.

Methods:
We enrolled CAD patients undergoing percutaneous coronary intervention (PCI) with available PFCS (measured by thromboelastography) and platelet reactivity (measured by VerifyNow). PFCS
High
was defined as maximal amplitude (MA)≥68, and high platelet reactivity (HPR) was categorized as P2Y12 reaction unit (PRU) >208. Patients were stratified into 4 groups according to the levels of MA and PRU: (1) normal platelet reactivity (NPR)-PFCS
Low
(31.9%); (2) HPR-PFCS
Low
(28.9%); (3) NPR-PFCS
High
(18.1%); and (4) HPR-PFCS
High
(21.1%). The primary endpoint was MACE (a composite of all-cause death, myocardial infarction, or stroke) and the risk of major bleeding was also evaluated.

Results:
At 4-year follow-up, prognostic implication of HPR and PFCS
High
showed the synergistic effect, and risks of MACE were significantly different across the groups (log-rank test,
P
< 0.001)
(Figure 1).
Compared with the NPR-PFCS
Low
group, the HPR-PFCS
High
group only showed a significantly higher risk of MACE (adjusted hazard ratio [HR
adj
]: 1.87; 95% confidence interval [CI]: 1.22-2.87; p=0.004). In addition, the HPR-PFCS
High
group had a greater rate of MACE compared with the HPR-PFCS
Low
group (HR
adj
: 1.47; 95% CI: 1.04-2.09; p=0.03). Similar results were revealed in the risk of all-cause death. Compared with HPR-PFCS
Low
, NPR-PFCS
Low
was associated with a higher major bleeding rate (HR
adj
: 3.03; 95% CI: 1.27-7.14; p=0.01).

Conclusions:
In PCI-treated patients, PFCS and HPR phenotypes show important relationships in the occurrence of adverse clinical events. Therefore, a combined assessment of clot strength and platelet reactivity may enhance post-PCI risk stratification.
Abstract 11437: False Atrial Fibrillation Alerts From Smartwatch in Relation to Perceived Physical Well-Being and Confidence in Management of Chronic Symptoms: The Pulsewatch Study
Authors: Noorishirazi Kamran , Dai Qiying , Mensah Otabil Edith , Wang Ziyue , Lessard Darleen , Mehawej Jordy , Filippaios Andreas , Paul Tenes J , Ding Eric , Naeem Syed , Soni Apurv , Saczynski Jane , Tran Khanh-van T , McManus David D
Published: June 2023

Background:
Atrial fibrillation (AF) can cause strokes that may be preventable with timely detection and anticoagulation therapy. Smartwatches offer the potential for non-invasive, long-term AF monitoring, but potential implications for psychological well-being associated with these alert systems remain to be studied. We examined the psychosocial impact of false alerts for AF on patients prescribed a smartwatch post stroke.

Methods:
We analyzed data from the Pulsewatch study (NCT03761394), which enrolled patients ≥50 years from the UMass Memorial Health system who had a history of stroke or transient ischemic attack, CHA
2
DS
2
-VASc ≥2, and no contraindications to anticoagulation. Data from participants in the intervention group, who received a cardiac patch monitor, as well as a smartwatch and smartphone installed with Pulsewatch applications, were analyzed. At baseline and 14 days, participants completed the Health Survey SF-12 to assess perceived physical well-being, and the Symptom Management survey to assess confidence in disease self-management. We employed logistic regression to assess changes in anxiety, perceived mental and physical health, and chronic disease management self-efficacy over 14 days with exposure to false alerts.

Results:
Among 85 participants who received a smartwatch for AF detection (mean age 64.8±9.2 years, 41% female, 86% non-Hispanic white) 11 (13%) received a false AF alert. Receipt of false alerts was associated with significant decreases in perceived physical well-being and management of chronic symptoms (β = -9.08, p < 0.01 and β = -6.50, p = 0.03, respectively), but not significantly associated with changes in perceived mental health (β = 0.70, p = 0.78).

Conclusions:
Perceived physical well-being and levels of disease self-management, but not perceived mental health, decreased with exposure to false AF alarms over 14 days. Further studies are required to explore the psychological impact of smartwatch AF monitoring in patients post stroke.
Abstract 11455: Outcomes of Latent Rheumatic Heart Disease: External Validation of a Simplified Score in Patients With And Without Secondary Prophylaxis
Authors: Nascimento Bruno R , Nunes Maria D , da Silva Jose Luiz Padilha , Steer Andrew , Engelman Daniel , Okello Emmy , Pulle Jafesi , Rwebembera Joselyn , Zuhlke Liesl , Mirabel Mariana , nakitto miriam , Sarnacki Rachel , Sable Craig A , Beaton Andrea Z
Published: June 2023

Background:
Secondary antibiotic prophylaxis reduces progression in children with latent rheumatic heart disease (RHD). However, nearly half of children show improvement with or without prophylaxis. Improved risk stratification could refine prophylaxis recommendations following positive screening echo. We aimed to validate a previously developed echo risk score to predict mid-term RHD outcomes among children with latent RHD.

Methods:
Our population included children who completed the GOAL Trial, a randomized controlled trial of secondary antibiotic prophylaxis among children with latent RHD in Uganda. These children underwent echo at enrollment and study completion, with rigorous blinded adjudication by a 4-member panel to establish diagnosis. We applied a point-based risk score developed from prior Brazilian and Ugandan cohorts, consisting of 5 variables (mitral valve (MV) anterior leaflet thickening (3 points), MV excessive leaflet tip motion (3), MV regurgitation jet length ≥2 cm (6), aortic valve focal thickening (4) and any aortic regurgitation (5)) to predict unfavorable outcome, defined as progression of diagnostic category (borderline to definite, definite mild valvular disease to definite moderate/severe disease) or remaining with definite RHD.

Results:
At total 801 patients (626 borderline and 175 definite RHD, mean age 12.5±2.9 years) were included, with median follow-up of 24 months. RHD progression was observed in 3 patients in the Penicillin group, vs. 33 in the control group, and overall, 386 patients regressed and 377 remained stable. The echo score was strongly associated with unfavorable outcome (OR: 1.25, 95% CI 1.15 - 1.36, p<0.001). Unfavorable outcome rates in low (≤6 points), intermediate (7 - 9) and high-risk (≥10) children at follow-up were 12.2%, 31.1%, and 42.2%, (p<0.001) respectively, with area under the ROC curve of 0.64 (95% CI 0.59 - 0.69). Among children without prophylaxis, the score had a similarly good performance: OR: 1.24 (95% CI 1.12 - 1.39), area under the ROC curve: 0.64 (95% CI 0.58 - 0.70).

Conclusions:
The simple risk score provided an accurate prediction of RHD status at 2-years, showing a good performance in a population with milder RHD phenotypes, with a potential value for global risk stratification.
Abstract 11470: Functional Validation of the Novel Role of SMARCB1 in Myocardial Fibrosis
Authors: Wang Min , Shabani Mahsima , Liu Duan , Sahni Jyotan , Pyfferoen Hazley J , Ac Lima Joao A , Pereira Naveen L
Published: June 2023

Introduction:
It has been previously demonstrated that cardiomyopathy predisposing common genetic variation in
SMARCB1
is associated with interstitial myocardial fibrosis (MF) as determined by cardiac MRI (CMR) linking the development of cardiomyopathy with MF.
SMARCB1
is known to be a tumor suppressor, but it’s role in the pathophysiology of MF and fibroblast physiology has not been functionally validated.

Hypothesis:
SMARCB1
plays an important role in regulating human cardiac fibroblast (HCF) differentiation/activation and collagen deposition, which are the critical steps in the development of MF.

Methods:
Cultured HCFs were treated with TGF-β1 (10ng/ml) for 48hrs to transdifferentiate into myofibroblasts, which are characterized by increased expression of α-smooth muscle actin (α-SMA, ACTA2) and collagen I (COL1A1). HCFs were transfected by siRNA using Lipofectamine™ RNAiMAX Transfection Reagent to knock-down (KD) the expression of
SMARCB1
. Total RNA and protein were extracted from cell lysate followed by qPCR and Western blot (WB) to quantify the expression level of SMARCB1, ACTA2 and COL1A1. Triplicate experiments were performed using biologically independent samples. For statistical analysis, a paired two-tail t-test was used.

Results:
HCFs treatment with TGF-β1, resulted in a significant decrease in expression of
SMARCB1
(p=0.031) with accompanying significant increase in expression of ACTA2 (p=0.025) and COL1A1 (p=0.0015) as compared to control by qPCR and WB.
SMARCB1
KD resulted in a further significant increase in expression of ACTA2 (p=0.018) and COL1A1 (p=0.028) as compared to non-target siRNA control group at both the transcript and protein level.

Conclusion:
We demonstrate for the first time that a gene associated with the development of cardiomyopathy
SMARCB1
mediates TGF-β1 induced cardiac fibrosis. These findings suggest
SMARCB1
as a potential therapeutic target to attenuate MF in cardiomyopathy.
Abstract 11497: Mineralocorticoid Receptor Antagonists and Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Oraii Alireza , Kowalik Krzysztof , Pandey Avinash K , Benz Alexander P , Wong Jorge A , Conen David , Healey Jeff S , McIntyre William F
Published: June 2023

Introduction:
Medical therapies to prevent atrial fibrillation (AF) episodes and to reduce heart failure (HF) or cardiovascular (CV) death in patients with AF are limited. The role of mineralocorticoid receptor antagonists (MRAs) in this population is unclear.
Objectives:
We aimed to assess whether the effect of MRAs (e.g. spironolactone, eplerenone, finerenone) in reducing cardiovascular events differs in patients with and without AF, and to evaluate the efficacy of MRAs in reducing AF events.

Methods:
We searched MEDLINE, Embase, and CENTRAL to March 2022 for randomized controlled trials (RCT) comparing an MRA to placebo or usual care in patients with established cardiovascular disease or risk factors. Pairs of reviewers systematically screened the eligible studies and used random-effects models to combine data.

Results:
We identified 6 RCTs including 7,245 participants (1,791 with AF and 5,454 without AF) that assessed the effect of MRAs on a composite of HF hospitalization or CV death (Figure). MRAs had similar efficacy for reducing HF hospitalization/CV death in patients with a history of AF (HR 0.86, 95% CI: 0.52-1.42; I
2
=71%) as compared to those without a history of AF (HR 0.77, 95% CI: 0.62-0.96; I
2
=58%) - P for subgroup differences=0.69. There was no evidence of difference in the efficacy of MRAs in reducing HF hospitalization (P for subgroup differences=0.93) and CV death (P for subgroup differences=0.41) in patients with and without AF. We identified 21 RCTs including 22,126 participants that reported on the occurrence of AF events. MRAs significantly reduced AF events (RR 0.78, 95% CI: 0.71-0.87; I
2
=0%). This effect was similar for reducing both new-onset AF (RR 0.81, 95% CI: 0.64-1.01; I
2
=32%) and recurrent AF episodes (RR 0.77, 95% CI: 0.67-0.88; I
2
=0%) - P for subgroup differences=0.71.

Conclusions:
MRAs reduce HF hospitalization or CV death to a similar extent in patients with and without AF. In addition, MRAs may prevent new-onset and recurrent AF events.
Abstract 11503: Obesity-Related Biomarkers Associations With HFpEF and Exercise Intolerance
Authors: Ramirez Fernandez Del Castillo Mariana , Lau Emily , Nayor Matthew G , Wang Dongyu , Shah Ravi V , McNeill Jenna , Lewis Gregory , Malhotra Rajeev , Ho Jennifer E
Published: June 2023

Background:
Obesity and adiposity are associated with risk of heart failure with preserved ejection fraction (HFpEF), yet the role of adipokines and other obesity related pathways as contributors to HFpEF remains unclear.
Objectives:
We sought to examine the association of obesity and obesity related biomarkers including adipokines, inflammatory markers, and insulin resistance with HFpEF and specific cardiac and extracardiac organ reserve measures among patients who underwent CPET.

Methods:
We studied 509 consecutive patients with LVEF ≥ 50% and NYHA class II - III symptoms, who underwent clinically indicated CPET with invasive hemodynamic monitoring. Fasting blood samples at the time of CPET were used to assay obesity-related biomarkers, including leptin, adiponectin, resistin, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), glucose and insulin to estimate insulin resistance (HOMA-IR). We examined the association of biomarkers with physiologic HFpEF and exercise traits using multivariable regression models.

Results:
Among 509 patients (mean age 55 years, 61% women, 38% obese), 223 met hemodynamic criteria for HFpEF. Obesity was associated with more than 2-fold higher odds of HFpEF (OR 2.08, 95% CI 1.38-3.14). We found that higher levels of leptin, hsCRP and HOMA-IR were associated with greater odds of HFpEF (P ≤ 0.01, Figure 1). By contrast, resistin and adiponectin were not associated with HFpEF (P>0.05). In secondary analyses, we observed associations of obesity related biomarkers with measures of impaired exercise capacity, such as lower peak VO
2
(P<0.05), higher blood pressure response (leptin, HOMA-IR), and impaired heart rate response (hsCRP, HOMA-IR, IL-6, resistin).

Conclusions:
Obesity related biomarkers were associated with HFpEF and impaired exercise capacity. These findings highlight potential pathways underlying the association of obesity and cardiometabolic disease with development of HFpEF.