bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11999: Molecular and Cellular Characterization of RyR2 Mutations Linked to Long-QT Syndrome
Authors: Cai Wenxuan , Valdivia Carmen R , Li Songhua , Booher Talia , Zheng Jingjing , Villarreal-Molina Teresa , Balderrábano-Saucedo Norma A , Medeiros-Domingo Argelia , Iturralde Pedro , Valdivia Hector H , Alvarado Francisco
Published: June 2023

Long-QT syndrome (LQTS) is a cardiac disorder characterized by prolonged QT interval and abnormal T waves on the electrocardiogram. Electrical abnormality can lead to severe arrhythmias, syncope and sudden cardiac death. Mutations in the Na
+
and K
+
channels or associated proteins account for the majority of cases; however, the genetic causes of about 20% of LQTS cases remain poorly understood. Recent genetic studies revealed novel LQTS-associated variants on the cardiac ryanodine receptor (RyR2), a Ca
2+
channel responsible for Ca
2+
-induced Ca
2+
release and excitation-contraction coupling. Given the important roles of RyR2 in the electrical activity of heart and previous evidence of RyR2 mutations in other inherited arrhythmias, we hypothesized that RyR2 mutations lead to functional alterations of the channels and contribute to dysregulated Ca
2+
release and pathological electrical remodeling. Eleven novel RyR2 mutations were identified in genetic studies of LQTS patients, including S166C, H877P, R1760W, G2094S, R2824W, R2920Q, R3673W, Y4287N, V4298M, P4534S and K4594Q. [3H] ryanodine (RyR2 ligand) binding assays revealed variable effects of the mutations on the opening probability of the RyR2 channel. In cell lines with stable expression of RyR2, Ca
2+
overload activates RyR2 channels and leads to spontaneous Ca
2+
release into the cytoplasm. Compared to WT RyR2, LQTS-associated RyR2 mutations cause an increase in the proportion of cells that exhibit spontaneous Ca
2+
release at various Ca
2+
concentrations, suggesting an increase in luminal Ca
2+
sensitivity of the channels. A transgenic mouse model carrying the R2920Q mutation was used to investigate the cellular and molecular pathways leading to LQTS. Homozygous mice showed prolonged QT interval and QTc at 5 months. Electrophysiological studies of the isolated cardiomyocytes revealed a depolarized resting membrane potential in the homozygous R2920Q cardiomyocytes and prolonged action potential duration in both heterozygous and homozygous R2920Q cardiomyocytes, compared to the WT cells. The availability of a mouse model that recapitulates the cardinal signs of LQTS will allow for deeper mechanistic insight into the role of RyR2 dysfunction as a driver of this arrhythmogenic syndrome.
Abstract 12: Identifying Emergency Medical Service Agencies In Black And Hispanic Communities With High Cardiac Arrest Survival Rates
Authors: Uzendu Anezi , Jones Philip , Spertus John , Chan Paul S
Published: June 2023

Background:
Black and Hispanic individuals have lower survival rates for out-of-hospital cardiac arrest (OHCA). Whether there are Emergency Medical Service (EMS) agencies in Black and Hispanic communities with high survival rates for OHCA is unknown but critical to identifying strategies to reduce racial and ethnic disparities in OHCA survival.

Methods:
Within the Cardiac Arrest Registry to Enhance Survival, we identified adults with non-traumatic OHCA during 2015-2019. EMS agencies were categorized as working in Black/Hispanic communities if >50% of residents in their catchment area were Black or Hispanic. Using hierarchical logistic regression, we calculated risk-standardized survival rates (RSSR) to hospital admission for OHCA in each EMS agency, adjusted for patients’ age, sex, witnessed arrest status, presumed arrest etiology, initial cardiac arrest rhythm, and arrest location. We then examined the distribution of EMS agencies that work in Black/Hispanic communities across quartiles of OHCA survival.

Results:
Among 764 EMS agencies (258,342 OHCAs), the median RSSR was 27.4% with an absolute difference of >10% across quartiles (median 22.4% in the lowest vs. 32.9% in the highest quartile; 191 EMS agencies in each quartile). There were 82 EMS agencies working in Black/Hispanic communities overall, with 26 (31.7%) in the lowest RSSR quartile and 15 (18.3%) in the highest. After further adjustment for agency-level rates of bystander CPR, EMS response time and termination of resuscitation practices, there remained 29 (35.4%) EMS agencies in the lowest RSSR quartile and 16 (19.5%) in the highest.

Conclusion:
EMS agencies working in Black and Hispanic communities have lower prehospital survival for OHCA, although high-performing agencies exist. Identifying best practices at EMS agencies with the highest prehospital survival rates, particularly among agencies serving Black and Hispanic communities, has the potential to improve overall OHCA survival and reduce existing survival disparities.
Abstract 120: Impact Of Mask Application On Aerosol Generation During Chest Compression And Defibrillation In A Swine Cardiac Arrest Model
Authors: Hsu Cindy H , Middleton Robert , McCracken Brendan M , Greer Nicholas , Cramer Traci , Boehman André L , Tiba Mohamad H , Wooldridge Margaret , Neumar Robert W
Published: June 2023

Introduction:
We previously demonstrated that defibrillation followed by chest compression generates more aerosols than chest compression or no-flow state alone. However, the best strategies to prevent aerosol spread during cardiac arrest (CA) resuscitation remain unknown. We hypothesized that mask applications could reduce aerosol spread during chest compressions and defibrillation in a swine CA model.

Methods:
To simulate witnessed CA with bystander-initiated CPR, 24 female non-intubated swine (43.8 [2.7] kg) underwent 4 minutes of untreated ventricular fibrillation CA followed by 10 two-minute cycles of mechanical chest compression and defibrillation without ventilation. The animals were randomized to receive no mask, cloth mask, surgical mask, N95 mask, or a sealed nose cone over their snouts during resuscitation (n=5/group except nose cone n=4). The diameter (0.3 - 10 μm) and quantity of particles generated during 45-second intervals of no-flow, chest compression, and after each defibrillation were measured 2 inches anterior to the snout.

Results:
There were no significant differences between total particles generated during chest compression after defibrillation in unmasked versus masked animals regardless of the mask type, while the nose cone significantly reduced total particles. These findings were consistent across all 10 defibrillations (Fig. 1a) and all particle sizes (Fig. 1b). Furthermore, the minimal pre- and post-defibrillation particles detected outside of the nose cone indicated that the ineffectiveness of masks in preventing aerosol spread during CA resuscitation was likely due to their inadequate fit (Fig. 1c).

Conclusion:
Mask application did not reduce aerosol spread during defibrillation followed by chest compression in a swine CA model. Our data indicate that mask fit is a critical parameter for reducing aerosol transport and do not support mask application on CA victims during bystander-initiated CPR.
Abstract 12004: Mitochondrial Fission Mediator MiD49 Regulates Proliferation via MYO1C in Pulmonary Arterial Hypertension
Authors: Chen Kuang-Huieh , Das Gupta Asish , Mewburn Jeffrey , Lima Patricia , Archer Stephen L
Published: June 2023

Introduction:
Pulmonary arterial hypertension (PAH) is a lethal syndrome characterized by pulmonary vascular obstruction that is partially due to hyperproliferation of apoptosis-resistant pulmonary arterial smooth muscle cells (PASMC). This “pseudoneoplastic phenotype” of PAH PASMC is due, in part, to excessive mitochondrial fission caused by activation of dynamin related protein-1 (Drp-1) and its binding partner MiD49. The mechanism by which MiD49 regulates the proliferation of PASMC is not completely understood. Here we investigate the possibility that MiD49 promotes cellular proliferation by regulating a non-filamentaous class-1 myosin protein, MYO1C.

Hypothesis:
MiD49 regulates cell proliferation via a MYO1C-dependent mechanism, which is pathologically upregulated in PAH.

Methods:
MiD49 and MYO1C expression was compared between normal (n=4) vs PAH (n=5) human PASMC using western blot analysis. The colocalization was visualized using super-resolution confocal microscopy. The effects of manipulating MYO1C on cell proliferation and apoptosis were assessed by flowcytometry.

Results:
MiD49 and MYO1C are upregulated and colocalized in PAH PASMC. The expression of MYO1C positively correlated with MiD49 in PAH. Silencing MiD49 downregulated MYO1C expression whilst augmenting MiD49 upregulated MYO1C. Silencing MYO1C, however, does not affect MiD49 expression, proving that MYO1C is downstream of MiD49. The downregulation of MYO1C by MiD49 silencing is rescued by a proteasomal blockade, MG132. Downregulating MYO1C using siRNA inhibited proliferation, prevented ERK1/2 activation, and induced apoptosis in PAH PASMC.

Conclusion:
Increased proliferation and apoptosis resistance of PAH PASMC are in part due to the dysregulation of MiD49-MYO1C pathway. Targeting this pathway may have therapeutic implications against PAH.
Abstract 12012: Subphenotypes of Heart Failure With Reduced Ejection Fraction Based on Repeated Measurements of 4210 Circulating Proteins Are Driven by Protein Subsets Reflecting Different Biological Mechanisms
Authors: Petersen Teun B , de Bakker Marie , Asselbergs Folkert W , Akkerhuis K. Martijn , Brugts Jasper J , van Ramshorst Jan , Lumbers Tom , Ostroff Rachel , Katsikis Peter D , van der Spek Peter J , Umans Victor A , Boersma Eric , Rizopoulos Dimitris , Kardys Isabella
Published: June 2023

Introduction:
Subphenotyping of HF may lead to pathophysiological insights and treatment opportunities. We aimed to identify novel circulating-protein based subphenotypes (SP) in patients with HFrEF. We used repeated proteomic assessments to account for the dynamic nature of HF.

Methods:
In 382 patients, we performed trimonthly blood sampling during a median follow-up of 2.1 years. We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, LVAD implantation, and heart transplantation) or censoring and applied an aptamer-based multiplex proteomic approach. We used unsupervised machine learning to derive subphenotypes from 4210 protein trajectories per patient represented by linear mixed effect intercept and slope coefficients.

Results:
We identified 4 SPs. SP1 was older with higher SBP, EF and history of hypertension. SP2 was older with lower SBP, lower EF, more comorbidities, and worse prognosis (adjHR(95% CI): 4.06 (2.07-7.96)) compared to SP1. SP3 was younger, had lower SBP and EF, more frequently cardiomyopathy (in particular dilated), and a worse prognosis (2.70 (1.33-5.48)). SP4 contained few patients and thus was harder to interpret. It differed from SP3 via higher SBP, higher EF, and seemingly better prognosis. SP allocation was driven by subsets of proteins associated with various biological functions and diseases, e.g. myocardial stress, inflammation, and renal dysfunction. Clinical characteristics of the SPs were aligned with these associations. The prognostic model using SPs based on repeated measurements had a better fit than using SPs based on baseline values (c-index: 0.78 vs 0.72).

Conclusions:
We found 4 circulating-protein based HFrEF subphenotypes driven by varying protein subsets, with different clinical characteristics and prognosis. Repeated protein measurements improved discriminative ability of the subphenotypes for clinical outcomes.
Abstract 12013: Nuclear Localization of PDGFRa Tyrosine Kinase Represents a Novel Mechanism Controlling the Fibrotic Response of Mesenchymal Stromal Cells to Myocardial Ischemia
Authors: Santini Maria Paola , Ishikawa Kiyotake , Azeloglu Evren
Published: June 2023

Background:
We discovered a time dependent dual role role for mesenchymal stromal cells expressing the platelet-derived growth factor alpha (PDGFRα
+
MSCs), which play essential functions in tissue revascularization and in fibro-adipogenic repair.

Hypothesis:
Based on our preliminary data, we hypothesized that specific and distinct stromal cells exist in the vertebrate heart, which retain regenerative capacities relevant to the extension of disease.

Methods:
All animal studies were performed in compliance with the regulations of the NIH and the local institutional animal care. Myocardial ischemia/reperfusion (MI/R) was induced in mice (n=10, FVB female mice) and pigs (n=10 female Yorkshire pigs) with standard procedures. Control animals were not operated (n=3 mice and n=4 pigs). Bulk RNA sequencing (n=4) was performed using a HiSeq2500 (Illumina).

Results:
Here, we showed that cardiac PDGFRα
+
MSCs have the potential to revascularize cardiac tissue and likely control cardiac electromechanical properties only earlier after MI/R. During the subacute phase, we discovered nuclear shuttling of the receptor from the plasma membrane before lineage specification into fibrotic cells (nuclear PDGFRα in non-ischemic 3±1
versus
ischemic 7.7±2.5 hearts; p<0.05). Interestingly, a similar response was observed in the heart of large animals (i.e., pigs), suggesting a cross-species mechanism controlling PDGFRα
+
MSCs commitment via intracellular shuffling of the tyrosine kinase receptor. A roadblock to the clinical translation of these discoveries is that there is no mechanism to manipulate PDGFRα
+
MSCs dual function. To cover this gap, we compared the transcriptomics of murine cardiac and skeletal muscle PDGFRα
+
MSCs using bulk RNA sequencing in physiological conditions. We discovered that key pathways, likely a signature of non-regenerating stromal cells, are differentially regulated in cardiac PDGFRα
+
MSCs, including Notch mediators of mesenchymal lineages and IGF-1 signaling.

Conclusions:
These data suggest that by modulating PDGFRα intracellular shuttling or altering the expression of specific genes, it may be possible to therapeutically direct PDGFRα
+
MSCs duality to reduce fibrosis, while harnessing their beneficial properties.
Abstract 12026: A Case of Eosinophilic Endomyocarditis in a Patient With Eosinophilic Leukemia and Hypereosinophilic Syndrome
Authors: Singh Navjot , Shah Ravi J , BANDYOPADHYAY DHRUBAJYOTI , Goel Akshay , Harburger Joseph , Ranjan Pragya
Published: June 2023

Background:
Eosinophilic (Loeffler’s) endomyocarditis is a restrictive cardiomyopathy caused by eosinophilic infiltration of myocardial. Complications include arrhythmias, intraventricular thrombus formation, and acute heart failure.

Clinical Presentation
A 37-year-old man with no past medical history presented with two weeks of fatigue and exertional dyspnea. He was found to have acute eosinophilic leukemia with a total white blood cell count of 440 k/mm^3 with 14% myelocytes, hypereosinophilic syndrome with an absolute eosinophil count of 56 k/mm^3, severe anemia and thrombocytopenia. Bone marrow biopsy and peripheral blood FISH analysis confirmed eosinophilic leukemia. He subsequently underwent leukopheresis, followed by treatment with hydroxyurea and imatinib.

Cardiac Evaluation
Echocardiogram revealed endomyocardial thickening of the left ventricular apex (Figure 1A). Cardiac MRI revealed left ventricular apical subendocardial wall thickness of 16 mm with subendocardial late gadolinium enhancement consistent with endomyocardial fibrosis (Figure 1B). The average global T1 value was 1100 ms and the calculated extracellular volume was 35%. MRI also revealed an apical left ventricular thrombus. The patient was treated with pulse dose of steroids in addition to the cancer-specific regimen. He did not initially receive anticoagulation due to severe anemia and thrombocytopenia. Subsequent echocardiography after three months of treatment revealed complete resolution of endomyocardial thickening and no evidence of a left ventricular thrombus. He had resolution of peripheral leukocytosis, hypereosinophilia, anemia, and thrombocytopenia.

Conclusion
This case presents the diagnosis and multidisciplinary management of eosinophilic endomyocarditis related to eosinophilic leukemia. Complete clinical and echocardiographic resolution was achieve following treatment with pulse-dose steroids and a cancer-specific regimen.
Abstract 12037: Tricuspid Annular Area and Leaflets Stretch Are Associated With Functional Tricuspid Regurgitation - Insights From Three-Dimensional Transesophageal Echocardiography
Authors: Ogawa Mana , ito asahiro , Ito Ayaka , Kim Andrew T , Ishikawa Sera , Iwata Shinichi , Takahashi Yosuke , Izumiya Yasuhiro , Shibata Toshihiko , Fukuda Daiju
Published: June 2023

Background:
The presence of functional tricuspid regurgitation (TR) is associated with mortality and morbidity. Although uniform management with a tricuspid annuloplasty ring is currently considered as a standard surgical procedure, high rates of residual TR despite annuloplasty are reported. Therefore, the identification of the TR mechanisms would be necessary to provide personalized treatment for each TR patient.

Methods:
This study population consisted of 106 patients with mitral regurgitation (MR) who were scheduled for procedure. Transthoracic and transesophageal echocardiography were performed prior to mitral valve intervention. We performed three-dimensional quantitative assessment including tricuspid annular (TA) area and the distance between the three commissures of tricuspid valve.

Results:
Moderate or greater TR was detected in 23 (22%). TA area (P < 0.01) and the distance between septum length (SL) (P = 0.02) and posterior length (PL) (p = 0.02) were significantly associated with moderate or greater TR, while TA diameter assessed using trans thoracic echocardiography was not. When patients were divided into four groups according to SL and PL, the group with longer SL and PL had greater risk of moderate or greater TR (P <0.01).

Conclusions:
Larger TA area and longer SL and PL, which represents limiting the amount of leaflet coaptation resulting from greater stretch of leaflets, are associated with functional TR in in patients with severe MR. The restoration of leaflet coaptation with autologous pericardial patch in addition to tricuspid annuloplasty ring may avoid or delay progression of residual TR and improve prognosis in patients with severe MR.
Abstract 12044: Injectable Contraceptive, Medroxyprogesterone Acetate, Produces Erratic Beating Patterns in Patient-Specific Re-Engineered Heart Cells With Type 2 Long QT Syndrome
Authors: Pinsky Alexa M , Gao Xiaozhi , Bains Sahej , Kim Changsung , Tester David J , Ackerman Michael J
Published: June 2023

Background:
Type 2 long QT syndrome (LQT2) is an inherited arrhythmia syndrome caused by pathogenic variants in the
KCNH2
gene which result in QT prolongation and confers susceptibility to arrhythmic syncope/seizures and sudden cardiac arrest/death. Oral progestin-based contraceptives increase the risk of cardiac events in women with LQT2 and we previously reported the case of a LQT2 woman with recurrent cardiac events attributed to the use of the progestin-based contraceptive, Medroxyprogesterone Acetate (“Depo-Provera”, Depo).

Objective:
To evaluate the arrhythmic-risk of Depo in a LQT2-specific, induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model.

Methods:
An iPSC-CM line was generated from the previously reported woman (KCNH2-G1006A*fs) as well as a control line. Voltage-sensing dye was used to assess the optical action potential duration (APD) with 10 μM Depo. 3-D erratic beating patterns were then assessed using multiple electrode array (MEA) with Depo and isoproterenol (ISO) to mimic an adrenergic surge.

Results:
Addition of Depo to the G1006A*fs iPSC-CMs decreased the optical APD from baseline 438±14 ms (n=6) to 363±35 ms (n=12; p=0.0001). Despite the APD shortening at baseline, in the setting of ISO, Depo administration induced erratic beating patterns in MEA, characterized as alternating spike amplitudes, alternans, or early after depolarization-like phenomena. Combined Depo and ISO treatment increased the percent of electrodes displaying erratic beating in G1006A*fs [baseline 8%±13 vs. Depo + ISO 38%±40 (p=0.0097)] but not in controls [baseline 2%±5 vs. Depo + ISO 7%±11 (p=0.14)]. Neither Depo nor ISO alone changed beating patterns in G1006A*fs [baseline 8%±13, Depo 30%±41 (p=0.08), ISO 21%±30, (p=0.17)] and controls [baseline 2%±5, Depo 3%±7 (p=0.61), ISO 0%±0 (p=0.4)].

Conclusion:
This patient-specific, re-engineered heart cell study provides a potential mechanism for the patient’s clinically documented, Depo-associated episodes of recurrent ventricular fibrillation. This in-vitro data should prompt a large-scale clinical assessment of Depo’s potential pro-arrhythmic effect in women with LQT2.
Abstract 12051: Anticoagulation Use After Percutaneous Left Atrial Appendage Occlusion in Medicare Beneficiaries
Authors: Blotner Michael , Ruzieh Mohammed , Jiao Tianze , Smolinski Nicole E , Naccarelli Gerald , Mandrola John M , Foy Andrew
Published: June 2023

Background:
In the pivotal trials of percutaneous left atrial appendage occlusion (pLAAO), patients received warfarin for 45 days followed by dual antiplatelets up to 6 months post pLAAO; however, real-world use of anticoagulants post pLAAO implantation is unknown.

Objectives:
To assess prescription anticoagulation and antiplatelet use after pLAAO in Medicare beneficiaries.

Methods:
We used a 15% sample of Medicare claims data (2015-2018) to identify patients who received pLAAO. Prescriptions claims were used to assess anticoagulant and antiplatelet use (other than over the counter aspirin) up to 12 months post pLAAO.

Results:
A total of 2,780 patients were included. The mean CHA2DS2-VASc score was 4.9. There were 2,171 (78.1%) patients who were prescribed anticoagulants after pLAAO. The most common drug was warfarin (63.8% of total anticoagulants used), followed by apixaban in 23.2% of the patients. At 3 months, 54.3% of the patients were taking a potent antithrombotic (anticoagulant or a P2Y12 inhibitor) medication. The number of patients taking potent antithrombotics decreased over time but remained high at 6 months (40.9%) and at 12 months (19.0%).

Conclusion:
Anticoagulation use remained high at 6- and 12-months post pLAAO; longer than what’s used in the pivotal trials. Further studies are needed to determine if this is associated with increased bleeding risk. Furthermore, this data should be taken into consideration when assessing stroke risk post pLAAO.
Abstract 12073: Electrical Storm Triggered by Car T-cell Therapy
Authors: Bennett Ari J , Koshy Thomas P , Daniels James D , Awan Farrukh T , Zaha Vlad G , Vallabhaneni Srilakshmi
Published: June 2023

Background:
Neither sustained VT nor electrical storm have been described in the setting of chimeric antigen receptor (CAR) T-cell therapy.

Case:
A 67-year-old man with a history of HFrEF (EF 47%), asymptomatic CAD with PCI to the RCA 18 years prior, hypertension, and metastatic synovial sarcoma status post anthracycline-based chemotherapy presented to our institution for CAR T-cell therapy. On treatment day 2, he developed high fevers unresponsive to acetaminophen, 3 doses of tocilizumab, IV dexamethasone, anakinra, and empiric broad spectrum antibiotics; his CRP at the time was 140.9 mg/L, consistent with severe cytokine release syndrome. On day 6, he felt new palpitations associated with frequent ten-second runs of NSVT. Notable labs included a flat hs-cTnI at 8 ng/L, NT-proBNP of 1,315 pg/mL, and Mg of 1.9 mg/dL. After 6 hours, the ectopy progressed to sustained, symptomatic monomorphic VT that initially responded to a 150 mg amiodarone bolus and drip, 25 mg of metoprolol tartrate q6h, and Mg repletion. Overnight, however, the patient developed multiple recurrences of the sustained VT. Amiodarone reloading and lidocaine bolus and drip successfully eliminated the ventricular ectopy. A subsequent cardiac MRI showed global hypokinesis with basal inferolateral akinesis; an LVEF of 38%; prolonged T1 and T2 parameters; and inferoseptal, inferior, and inferolateral delayed enhancement consistent with ischemic cardiomyopathy. An EP study elicited multiple sustained, hemodynamically unstable monomorphic VTs with changing QRS morphologies by programmed stimulation, so a dual chamber ICD was implanted. Finally, a coronary CTA revealed CTO of a mid RCA stent. The patient was discharged on amiodarone and metoprolol—as well as guideline-directed medical therapy for his CAD and HFrEF—without any VT recurrence on follow-up.

Conclusion:
Electrical storm is a previously undescribed complication of CAR T-cell therapy. The presumed mechanism for VT in this case was ischemic scar-mediated reentry triggered by cytokine release syndrome. This case highlights a potential role for myocardial tissue characterization with multiparametric cardiac MRI, in addition to ischemic evaluation, in high-risk patients prior to CAR T-cell therapy.
Abstract 12077: Impact of Overweight and Obesity on Left Ventricular Structure and Function in a Community Dwelling Cohort Free of Cardiovascular Disease
Authors: Qazi Saadia , Gona Philimon N , Lee Jane J , Tsao Connie , Salton Carol , ODonnell Christopher , Manning Warren J , Chuang Michael L
Published: June 2023

Introduction:
Obesity is associated with excess cardiovascular morbidity and mortality as well as structural and functional differences in left ventricular (LV) mass (LVM), end-diastolic volume (LVEDV), and stroke volume despite indexation.

Hypothesis:
We hypothesize that overweight and obesity impact LV structure and function in a healthy community dwelling cohort.

Methods:
Framingham Offspring study participants (N=678, 62%F; 65±9y) free of any history of hypertension, myocardial infarction, heart failure, or CMR wall-motion abnormality and underwent bSSFP CMR at 1.5T. They were stratified by sex and body mass index (BMI) category (normal weight =18.5 to 24.9; overweight =25.0 to 29.9; obese ≥30 kg/m
2
). LVM was measured from contiguous short-axis images, then indexed to height (HT, m), body surface area (BSA, m
2
), and weight (WT, kg). We calculated myocardial contraction fraction (MCF), a marker of LV myocardial shortening, as LV stroke volume divided by LV myocardial volume. The ratio of LVM/LVEDV was used as a measure of LV concentricity to evaluate LV structure.

Results:
The Table shows MCF, LV concentricity, and indexed LVM (LVMi) stratified by BMI. WT-indexation resulted in a declining LVMi with increasing BMI in both men and women. However, indexation to HT showed an increasing LVMi with higher BMI. BSA-indexation remained consistent across BMI categories in both men and women. MCF decreased and concentricity increased with increasing BMI in both sexes.

Conclusion:
The association of LVMi with BMI varies by indexation method. In a healthy, community-dwelling cohort, BSA yields “consistent” LVM indexation across BMI categories. However, MCF decreased, and concentricity increased with increasing categories of BMI. These adverse alterations of MCF and concentricity may provide insight into obesity-related LV remodeling, whereas consideration of LVM alone may not. These data lay the groundwork for further outcomes analyses in this population.
Abstract 12083: Highly Caffeinated Energy Drinks and Genetic Heart Disease-Associated Sudden Cardiac Arrest
Authors: Bains Sahej , Bos Johan M , Tester David J , MacIntyre Ciorsti , Giudicessi John , Ackerman Michael J
Published: June 2023

Background:
Highly caffeinated energy drinks (HCEDs) can trigger life-threatening cardiac arrhythmias in individuals with and without an underlying genetic predisposition. Though the mechanism(s) responsible for these events remain unclear, it has been postulated that high caffeine may alter heart rate, blood pressure, cardiac contractility, and cardiac repolarization in a manner that is pro-arrhythmic.

Objective:
To describe our experience regarding sudden cardiac arrest (SCA) events occurring in proximity to HCED consumption in patients with underling genetic heart diseases.

Methods:
All SCA survivors referred to the Mayo Clinic Windland Smith Rice Genetic Heart Rhythm Clinic for clinical and/or molecular evaluation were reviewed to identify those with a history of HCED consumption prior to their event. Patient demographics, clinical characteristics, documented HCED consumption, and temporal relationship of HCED consumption to SCA were extracted from the electronic medical record.

Results:
Among 144 SCA survivors with a structurally normal heart, 8 (6 females; mean age at event 28 ± 8 years) experienced an unexplained SCA associated temporally with HCED consumption. Of these, 5 (63%) had either long QT syndrome (n=3) or catecholaminergic polymorphic ventricular tachycardia (n=2). The remaining 3 were diagnosed with unexplained SCA/idiopathic ventricular fibrillation after a comprehensive evaluation. Three patients (37%) were habitual HCED consumers while 5 (63%) imbibed for the first time with consumption ranging from several hours to a few minutes before the SCA. Seven patients (88%) required a rescue shock (average 2 ± 2 shocks/patient) while 1 was manually resuscitated. Upon follow-up, 6 (75%) were dismissed with an implantable cardioverter defibrillator, 1 (13%) on pharmacologic therapy, and 1 (13%) underwent denervation surgery. All SCA survivors have quit drinking HCEDs and have been event-free since.

Conclusion:
Overall, 8/144 (5.6%) of SCA survivors evaluated in our program experienced a SCA in proximity to consuming a HCED. Although larger cohort studies are needed to elucidate the precise mechanism for HCED-triggered/associated SCA and quantify its precise pro-arrhythmic risk, it seems prudent to sound an early warning.
Abstract 12085: Cardiac Structural and Functional Differences Between the Types of Sleep Apnea in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Yatsu Shoichito , Horvath Christian , Tobushi Tomoyuki , Woo Anna , Floras John , Logan Alexander G , Bradley Douglas ,   The ADVENT-HF investigators
Published: June 2023

Introduction:
In patients with heart failure with reduced ejection fraction (HFrEF), sleep-disordered breathing (SDB) may affect, or be affected by cardiac structure and function. We hypothesized that patients with OSA would demonstrate left ventricular (LV) remodeling and impaired LV function intermediate between that of patients with CSA and patients with no SDB.

Methods:
ADVENT-HF is a multinational randomized trial investigating the effect of adaptive servo ventilation in patients with HFrEF and SDB. Inclusion required LV ejection fraction (LVEF) ≤45%, and a polysomnographic (PSG) apnea-hypopnea index (AHI) ≥15. Subjects with an AHI <15 were excluded from randomization but comprised a no-SDB (NSDB) group. All transthoracic echocardiograms (TTE) and PSGs were analyzed in core laboratories at University Health Network in Toronto. Patients with SDB were subdivided into those with OSA and those with CSA. We then compared baseline demographic and TTE characteristics of the NSDB, OSA and CSA cohorts.

Results:
Among them, 665 with acceptable TTE were analyzed. As shown in the table, the CSA group was older, more predominantly male, and had a higher AHI than the other groups, and a higher prevalence of atrial fibrillation and a lower minimum arterial oxyhemoglobin saturation level than the NSDB group. The CSA group also had greater LV mass index than the other groups, greater LV volume indices and lower LVEF than the OSA group, and lower cardiac index than the NSDB group. Although the OSA group had no significant differences in TTE findings compared to the NSDB group, the OSA group was older, more predominantly male, and had a greater AHI than the NSDB group and a higher BMI than the CSA group and lower minSaO
2
than the other groups.

Conclusion:
In patients with HFrEF, the degree of LV remodeling and dysfunction did not differ between the OSA and NSDB groups, but those with CSA had more advanced LV remodeling and dysfunction than the other groups signaling more advanced HF.
Abstract 12090: Catheter Ablation Impairs Left Atrial Function in Patients With Atrial Fibrillation: A Magnetic Resonance Imaging Study
Authors: Chahine Yaacoub , Macheret Fima , Bockus Lee , Kim Joonseok , Akoum Nazem W
Published: June 2023

Introduction:
Atrial fibrillation (AF) is associated with left atrial (LA) fibrosis and morphological remodeling. Catheter ablation (CA) is a well-established method of treatment for AF which results in additional LA scarring. Cardiac magnetic resonance (CMR) imaging is the gold standard for evaluating LA volumes and function, and feature tracking in CMR has been increasingly confirmed as a feasible and reproducible technique for assessing LA function through strain. We used CMR to assess baseline fibrosis, ablation-induced scarring and the impact of CA on LA volume, shape and function in patients with AF undergoing their first catheter ablation.

Methods:
AF patients underwent late gadolinium enhancement CMR prior to, then at least 3 months after CA for quantification of LA volumes, fibrosis and ablation-induced scarring, respectively (Panel A). Global longitudinal reservoir strain (GLRS) was assessed by feature tracking (Panel B). Cine-images were used to assess sphericity and emptying fraction. All CMR images were obtained in sinus rhythm. Wilcoxon signed rank analysis was used to assess the effect of CA on LA volume and sphericity index, emptying fraction and GLRS.

Results:
40 patients (57% male, average age 61.9 years, 72.5% paroxysmal AF) were included. Pre-ablation LA fibrosis was 16.6% [9.1, 20.7] whereas ablation-induced LA scar was 8.0% [6.5, 12.1]. GLRS and LA emptying fraction decreased after CA (17.8 [15.3, 20.5] vs 16.0 [13.5, 19.0] p=0.006, and 60.2% [51.3, 66.4] vs 51.6% [46.3, 61.1], p<0.001, respectively). However, LA volume index and sphericity index were unchanged after CA in our study cohort (48.0 mL/m
2
[37.1, 61.1] vs 47.0 mL/m
2
[36.2, 52.7] p=0.91 and 54.6% [47.2, 65.4] vs 53.2% [46.5, 64.5] p=0.8, respectively) (Panel C).

Conclusion:
LA function is negatively impacted by catheter ablation for AF. The competing impact of ablation on rhythm control and atrial function with respect to stroke and heart failure need to be further evaluated.
Abstract 121: Covid-19 Cardiac Arrest: Resuscitate Or Not?
Authors: Ramirez Claudia M , Ziad Mohamed , Almaguer Angelica , Bhalla Sushen , Gonzalez Jesus , Canete Cruz Ailine , Emeaba Ndiya , Akinwale David , Varon Daryelle , Alshami Abbas , Varon Joseph
Published: June 2023

Introduction:
Coronavirus disease 2019 (COVID-19) has been associated with high in-hospital mortality. Since the implementation of guidelines and improvement in the quality of cardiopulmonary resuscitation (CPR), the survival rate for non-COVID-19 patients has improved. There is, however, scarce data regarding in-hospital cardiac arrest outcomes in COVID-19 patients. This study aimed to investigate cardiac arrest outcomes in patients hospitalized for COVID-19.

Methods:
Retrospective study of the data of 994 adult patients admitted to a single-center high acuity critical care COVID -19 unit between March 2020 and February 2022 with COVID-19 diagnosis. Patients who underwent CPR were identified. Resuscitation registers and demographic information were obtained. The primary outcome was survival to hospital discharge. Secondary assessments were the initial rhythm and duration of CPR. Descriptive statistics were utilized.

Results:
A total of 994 COVID-19 patients were included in the study. 129 (13%) had a cardiac arrest and underwent CPR. Two patients survived hospital discharge (1.6%). Of them, 91(70.5%) were male. Mean age was 68.6 (+/- 13.5) years. Median BMI was 29.1 [25.8-35.7] Kg/m
2
. The most frequent comorbidity was hypertension in 59 patients (46.1%), followed by diabetes type 2 in 30 patients (23.4%), and there were 37 (28.9%) patients with no comorbidities. The median time from admission to cardiac arrest was 12[6-18.5] days, the most common rhythm at the time of cardiac arrest was asystole in 94 (72.9%) patients, followed by pulseless electrical activity in 25 (19.4%); Ventricular dysrhythmias occurred in 7 (5.5%)of the cases. Finally, the median duration of CPR was 20[13.7-29] minutes.

Conclusions:
Survival of COVID-19 patients after in-hospital cardiac arrest was dismal, despite the adequate implementation of resuscitation protocols. Many of these patients were overweight or obese with comorbid conditions. The most common presenting rhythm was a non-shockable rhythm.
Abstract 12106: Electrocardiographic Imaging Accuracy and Coherence Between Two Different Systems
Authors: Parreira Leonor , Carmo Pedro , Mesquita Dinis , Marinheiro Rita , Marques Lia , Mancelos Sofia , Hitchen Rebecca , Ferreira Antonio , Chmelevsky Mikhail , Zubarev Stepan , Araujo Goncalves Pedro , Marques Hugo , Adragao Pedro
Published: June 2023

Introduction:
Previous studies reporting on electrocardiographic imaging (ECGI), using an epicardial-only system, have suggested a bad accuracy

Hypothesis:
Assess the accuracy and coherence of two endo-epicardial ECGI systems using different cardiac sources.

Methods:
We performed 61 ECGI procedures in 48 patients referred for ablation of frequent idiopathic premature ventricular contractions (PVCs) at our center. The Amycard (EP Solutions SA, Switzerland) system based on the extracellular potential, was used in 26 patients, the VIVO (Catheter Precision, NJ USA) systems based on the equivalent double layer model in 9, and both in 13 patients. The localisation of the PVCs based on ECGI was done using a segmental model with 22 segments on the left ventricle, to include the classical 17 segment model plus the aortic cusps and the papillary muscles, and 12 segments on the right ventricle including 4 on the right ventricular outflow tract (RVOT). A perfect match (PM) was defined as a predicted location within the same anatomic segment, whereas a near match (NM) as a predicted location within the same segment or a contiguous one.

Results:
Ablation was performed in 42 patients, successful in 76%. The origin of the PVCs was the RVOT in 22 patients, right ventricle in 5, coronary cusps in 3, left ventricle in 3, LV summit in 3, LVOT in 2, papillary muscles in 2, moderator band in 1 and aortomitral continuity in 1. The agreement between the predicted site and the invasive mapping with both systems is depicted in the table. The percentage of PM and NM was not significantly different. In the 13 patients that had the ECGI performed with both systems, we found a NM in 100% and a PM in 70%. (Figure).

Conclusions:
ECGI is an accurate diagnostic tool with reproducible results regardless the cardiac source used for analysis.
Abstract 12116: Effects of Interleukin-1 Blockade With Anakinra on Peak Oxygen Consumption in Patients With Heart Failure an Analysis of On-Treatment and Off-Treatment Assessments
Authors: Van Tassel Benjamin , Moroni Francesco , pinel Sebastian , Carbone Salvatore , TRANKLE Cory R , Billingsley Hayley E , Talasaz Azita , Kontos Michael C , Roberts Charlotte , Arena Ross A , Canada Justin M , Abbate Antonio
Published: June 2023

Introduction:
Interleukin-1 (IL-1) blockade may improve exercise capacity in the subset of heart failure (HF) patient with high inflammation. Accordingly, modulating systemic inflammation with IL-1 inhibition could result in physiologic adaptations that have a beneficial effect on exercise capacity in this population.

Hypothesis:
Primary objective of the study was to determine changes in peak oxygen consumption (VO2) on-treatment with anakinra, an IL-1 blocker, and after treatment cessation.

Methods:
Cardiopulmonary exercise testing (CPET) was performed in 52 patients with HF at baseline, during daily treatment and after suspension of treatment with 100 mg anakinra. High-sensitivity C-reactive protein (CRP) was measured at the time of each CPET. Data are presented as median and interquartile range or number and percentage.

Results:
The cohort included twenty-six (50%) females, 36 (69%) self-identified as Black/African-American, 55 [52-62] years. Left ventricular ejection fraction (LVEF) was 43% [34-60%], CRP was 7.1 [3.7-15.8] mg/L and peak VO2 was 14.5 [12.6-17.4] ml•kg-1•min-1. Treatment duration was 4 [2-12] weeks, while time between treatment discontinuation and off-treatment CPET was 12 [6-12] weeks. Treatment with anakinra significantly reduced CRP (7.1 [3.7-15.8] to 1.5 [1.0-3.8] mg/L, p<0.001) and improved peak VO2 (14.5 [12.6-17.4] ml•kg-1•min-1to 16.0 [14.0-18.6] ml•kg-1•min-1, p=0.011-Figures A and B, respectively). CRP significantly increased to 3.8 [1.4-10.7] mg/L, p=0.007, and peak VO2 significantly decreased to 15.5 [12-17.8] ml•kg-1•min-1 (p= 0.004) after anakinra suspension.

Conclusions:
IL-1 blockade with anakinra is associated with a reduction in systemic inflammation (CRP levels) and in an improvement in exercise capacity (i.e., peak VO2) among patients with HF during treatment. These data validate IL-1 blockade as a mediator of exercise capacity in HF; however long-term effects require further investigation.
Abstract 12132: Utility of a Proteomic Surrogate for Cardiovascular Outcomes to Predict and Monitor COVID-19 Induced Myocarditis
Authors: Paterson Clare , Hinterberg Michael A , Morrow Andrew J , Sykes Robert , Mangion Kenneth , Welsh Paul , McConnachie Alex , Sattar Naveed , Berry Colin , Williams Stephen A
Published: June 2023

Introduction:
Poorer cardiovascular (CV) health is a risk factor for adverse outcomes from COVID-19, and a proportion of COVID-19 survivors exhibit CV dysfunction including myocardial inflammation after initial recovery. However, biomarker-driven predictors of CV outcomes in COVID-19 are lacking. We recently demonstrated that a proteomic surrogate of CV outcomes (MI, stroke, hospitalization for heart failure, or death within 4 years) is highly predictive of acute COVID-19 severity. The current study expands on this to determine if a proteomic CV risk test associates with myocarditis likelihood in COVID-19 survivors.

Methods:
The SomaScan® platform was used for plasma proteomic phenotyping in CISCO-19 trial participants (n=154, mean age 55y, 43% Female) at hospital discharge following COVID-19, and at follow-up within 6-months later when comprehensive CV assessment including cardiac MRI for myocarditis adjudication was performed. N=20 (13%) were classified as very likely to have myocarditis at follow-up. We used linear mixed models to test proteomic CV scores at both visits against myocarditis likelihood across COVID-19 recovery and compared the predictive performance of the CV risk score to discriminate myocarditis likelihood to performance of Troponin I (TnI) and NT-proBNP.

Results:
A 36% relative CV risk reduction was observed during COVID-19 recovery. CV risk scores were significantly higher among those very likely myocarditis positive at follow up (p < 0.05 for effects) (
Figure 1
). Additionally, the performance of the CV risk test in classifying myocarditis likelihood at follow-up was superior to that of TnI or NT-proBNP (AUC=0.64 vs 0.52 and 0.51, respectively).

Conclusions:
A proteomic predictor of CV risk has potential to support cardiac screening and monitoring CV health across the course of COVID-19 recovery, with diagnostic specificity superior to that of specific single cardiac biomarkers. Future studies with this approach seem warranted.
Abstract 12136: Multiple Blood Biomarker Approach for Risk Stratification in Patients With Low-Flow Low-Gradient Aortic Stenosis
Authors: Abdeldjebbar Yassine , Hecht Sebastien , Dahou Abdellaziz , Annabi Mohamed-salah , bernier mathieu , Beaudoin Jonathan , Cote Nancy , OConnor Kim , Larose Eric , Rodes-Cabau Josep , Mathieu Patrick , Clavel Marie-Annick , Pibarot Philippe
Published: June 2023

Background and Objectives:
Previous studies have shown that a multiple blood biomarker strategy prior to aortic valve replacement (AVR) may be useful for risk stratification in patients undergoing surgical AVR (SAVR). The usefulness of this approach in patients with low-flow low-gradient aortic stenosis (LF-LG AS) has not been examined. The objective of this study was to determine the prognostic value of combined measures of multiple blood biomarkers in patients with LF-LG AS treated conservatively or by AVR.

Methods:
168 patients were prospectively enrolled in the TOPAS (Truly or Pseudo-severe Aortic Stenosis) study at our institute. Clinical and echocardiographic data were collected for each patient. Eight biomarkers of myocardial stress, inflammation, renal function (brain natriuretic peptide, creatine kinase-mb, interleukin-6, alanine transaminase, lactate dehydrogenase, alkaline phosphatase, procalcitonin, ferritin) were measured from blood samples collected at baseline. The cohort was divided into 3 groups according to the number of elevated biomarkers. Uni- and multivariable survival analyses were performed to evaluate the association between the number of elevated biomarkers and all-cause mortality.

Results:
Mean age was 73 years (68% male). After a median follow-up of 3.41 years, 69 (35%) patients died. Patients with 0-3, 4-6, and >6 elevated biomarkers had 8 years survival estimates of 75%, 52%, and 19%, respectively (log-rank p<0.0001). Using multivariable Cox analysis adjusted for age, sex, BMI, AVR as a time-dependent variable, renal function and STS score, patients with >6 elevated biomarkers had an increased risk of all-cause mortality as compared to the group of patients with 0-3 elevated biomarkers (referent group), HR=3.82, p<.0001, and as compared to the group of patients with 4-6 elevated biomarkers HR=2.81, p<.0001. There was no significant difference in all-cause mortality between patients with 4-6 elevated biomarkers and the referent group p=0.38.

Conclusion:
In this series of patients with LF-LG AS, a higher number of elevated biomarkers was associated with an increased rate of mortality. These results suggest that a multiple blood biomarkers approach may be useful to enhance the risk stratification in this cohort.
Abstract 12154: Relationship Between Caffeine Consumption and Young Athletes' Comorbidities, Exercise-Related Symptoms, and Baseline Electrocardiogram
Authors: Farber Jason , Dikdan Sean , Ruge Max , Johnson Drew , Shipon David
Published: June 2023

Introduction:
Studies on adult athletes have found that caffeine consumption has both positive and negative effects on physical performance and cardiovascular physiology. While roughly 3 in 4 children older than 5 years old consume caffeinated beverages, the effects of caffeine on children and adolescent athletes are less studied.

Methods:
The HeartBytes National Youth Database produced by Simon’s Heart, a nonprofit organization that organizes pre-participation examinations (PPEs) of adolescents, was utilized for this study. This database contains demographic, exercise-related symptom (chest pain or dyspnea), and electrocardiogram data obtained during Simon’s Heart PPEs. Logistic regression models were adjusted for age, BMI, race, and gender except for the model assessing BMI as an outcome, which adjusted only for age, race, and gender.

Results:
Of the 7425 patients in the HeartBytes database, the majority were male (60.6%) and White (83.9%). The median age was 15.0 years old (interquartile range 13.5 - 16.5). Those who consumed caffeine were more likely to have a history of ADHD (adjusted odds ratio [aOR] 1.43 [CI: 1.15 - 1.76]; p = 0.001) and a BMI ≥ 30 (aOR 1.69 [CI: 1.27 - 2.25]; p < 0.001) when compared to non-caffeine drinkers. Caffeine drinkers overall were at no higher risk for exercise-related symptoms. However, when type of beverage was assessed, soda drinkers were more likely to have symptoms during exercise (aOR 1.33 [CI: 1.02 - 1.73]; p = 0.032) and coffee drinkers were more likely to have syncope with exercise (aOR 2.13 [CI: 1.20 - 3.60]; p = 0.006) compared to those who do not consume caffeinated beverages. No association was present between caffeine consumption or beverage type and ECG changes.

Conclusions:
In this dataset from a national registry of PPEs, caffeine consumption was independently associated with obesity and ADHD. While caffeine consumption itself did not increase risk of exercise-related symptoms, soda drinkers were at higher risk for symptoms during exercise, and coffee drinkers were at higher risk of syncope with exercise. The study shows that caffeine consumption may have significant impact on youth health. Future studies are needed to further confirm our findings.