bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12820: Utilization of Cardiac Magnetic Resonance Imaging for Management of Coronary Chronic Total Occlusions
Authors: Drescher Caitlin S , Chamis Anna Lisa , Patolia Harsh , Tanaka John , Tannu Manasi , Othman Islam , Jones William S , Rymer Jennifer A
Published: June 2023

Introduction:
Revascularization of coronary chronic total occlusions (CTOs) may be indicated for relief of medically refractory angina. Myocardial viability assessment by cardiac magnetic resonance (CMR) may help select patients for CTO intervention. Real-world practice is not well described.

Methods:
We identified patients who underwent coronary angiography between 2016-2020 at a large tertiary center and had ≥1 CTO. Patients with prior CABG were excluded. We examined rates of CMR and outcomes including revascularization and MACE. Myocardial segments were attributed to a CTO territory and adjudicated following angiographic review of coronary anatomy. Significant CMR viability was defined as <50% transmural delayed enhancement in the CTO territory.

Results:
We identified 1279 patients (74.1% male, 28.1% Black) who met inclusion criteria. Of these, 36.0% had type 2 diabetes mellitus and 54.9% reported angina pectoris. Over half of patients had CTO of the RCA (56.5%), and 18.5% of patients had CTO in >1 vessel. Non-invasive testing was performed in 38.4% of patients; 10.8% had CMR. Rates of CMR were higher in patients with severely reduced EF (≤35%) compared to those with normal EF (≥55%) (22.1% vs 11.1%; p<0.001). Among those who had CMR, 84.8% of patients showed significant viability in the CTO territory (Fig). CTO PCI was performed in 12.5% of patients, CABG was performed in 24.9%, and 63.2% were managed medically. Patients who had CTO PCI had higher rates of angina versus those without CTO PCI (70.0% vs 52.8%; p<0.001) and were more likely to be on ≥2 anti-anginal medications (30.6% vs 18.9%; p<0.001). CTO PCI technical success was achieved in 69.5% of patients and MACE occurred in 2.3% of cases.

Conclusions:
Patients with coronary CTOs demonstrate high rates of viability in CTO territories based on CMR. Rates of viability testing and CTO revascularization remain low. Further work is needed to determine the role of CMR and other non-invasive testing in CTO management.
Abstract 12834: Hospital Variation in Implantation of Permanent Pacemaker After Transcatheter Aortic Valve Implantation: An Insight From the US Nationwide Readmission Database
Authors: Sanchez-Nadales Alejandro , Zahid Salman , Uppal Dipan , Lewis Antonio , Sleiman Jose R , Asher Craig R , Baez-Escudero Jose L
Published: June 2023

Background:
Pacemaker implantation (PPM) remains the most common complication after TAVI. However, the relationship between hospital volume of TAVI discharge and PPM implantation remains unknown.

Methods and Results:
The purpose of this study was to evaluate the association between annual TAVI discharge volumes with 30-day incidence of PPM implantation. We utilized the most recent available 2018 US Nationwide Readmission Database. International Classification of Diseases ICD-10 codes were used to identify all hospitalizations. We categorized hospitals performing <100 cases per year as low-volume; 100 to 200 as medium-volume and >200 high-volume facilities. A total of 34,740 non-weighted TAVI hospitalizations were included in this analysis. Of the included cases, 37.5% (13,024) were performed in low volume centers, whereas 31.3% (10,862) and 31.2% (10,854) cases were performed in medium and high-volume centers. The overall 30-day rate of PPM Implantations was 19.5% (6,771). On adjusted analysis there was no difference between high (OR 1.01, 95% CI 0.95-1.08) and medium volume (OR 1.02, 95% CI 0.95-1.09) centers when compared to low volume centers respectively. Moreover, cumulative incidence curves showed similar rates of readmission for PPM implantations (Figure 1: P log rank 0.20).

Conclusions:
PPM implantation rates remain high post TAVI. Higher volume of TAVI discharge does not result in fewer PPM implantations. Further studies and interventions are required to reduce PPM implantation after TAVI.
Abstract 12868: Real-Time Explainable Detection of Stenosis in Coronary Angiography
Authors: Dufendach Keith A , Erickson Emma , Morales Garza Cecilia , Edman Robert , Kaczorowski David , Dubrawski Artur
Published: June 2023

Background:
Coronary angiography is the gold standard for evaluating coronary artery disease and determining the appropriate treatment strategy for a patient. The aim of this study is to use a machine learning (ML)-based object detection algorithm to identify images with clinically significant stenoses and provide explainable output by localizing the area of stenosis within each image.

Methods:
We utilize the YOLOv5 object detection algorithm to detect clinically significant stenoses by treating narrowing of the vessel as the object to be located in an image. Models are trained utilizing a 5-fold cross-validation strategy on a dataset consisting of the middle frame from 756 randomly selected cine clips from an interventional cardiology suite. Maximum object confidence on the validation dataset is used for downstream whole image classification.

Results:
Across 5 folds, mean bounding box precision was 0.342 ± 0.074 and recall was 0.305 ± 0.021 at an intersection over union threshold of 0.6. The image classification model achieved a mean and standard deviation area under the receiver operating characteristic curve of 0.863 ± 0.042 with a mean accuracy of 0.809 ± 0.041 at the optimal confidence cutoff of 0.283 ± 0.241. Additionally, trained model predictions occurred at a rate of 32.8 ± 3.6 frames per second, allowing for live model inference and provider support at a standard angiographic frame rate of 15 frames per second.

Conclusions:
The proposed object detection ML approach is a time-efficient and data-efficient method of diagnosing significant coronary artery stenosis. These results combine state-of-the-art performance in detecting stenosis in angiographic images with improved explainability over single-step classification with a deep neural network.
Abstract 12900: To Rescue or Not to Rescue? Multiple MitraClips for Ruptured Chordae on VA-ECMO
Authors: Baer Jacob , Dalia Tarun , Shah Zubair , Tadros Peter , Wiley Mark A , Zorn Trip , Berenbom Loren D , Gupta Bhanu
Published: June 2023

Background:
Role of MitraClip as rescue therapy in patients with severe mitral regurgitation (MR) in the setting of ruptured chordae with profound cardiogenic shock in hypertrophic obstructive cardiomyopathy (HOCM) is not well known.

Case:
60-year-old male presented with profound cardiogenic shock requiring ECMO with severe lactic acidosis. Past medical history included HOCM s/p septal ablation and ICD, mild MR, a-fib s/p watchman, and CKD stage 3.Transesophageal echocardiogram demonstrated a flail posterior mitral valve leaflet due to ruptured chordae tendineae with anteriorly directed jet of severe MR (figure 1A). VA-ECMO was initiated for profound hypotension. 3 MitraClips were required as rescue strategy as the patient was deemed too critical to undergo surgical repair. Post procedure, MR was mild with a mean MV gradient of 4 mmHg at the end of the procedure (figure 1B). 15 months post-hospitalization, patient reported dyspnea on exertion. Exercise stress echo revealed a mean MV resting gradient of 7 mmHg that increased to 16 mmHg at 50 W exercise (figure 1C). Invasive hemodynamics showed a mean gradient of 12 mmHg between LV end-diastolic pressure and pulmonary capillary wedge pressure (figure 1D) confirming severe mitral stenosis. The patient is currently being evaluated for surgical MV replacement.

Discussion:
Transcatheter edge-to-edge mitral valve repair (TMVr) has been studied extensively in patients with dilated cardiomyopathy, and chronic stable severe MR. There is limited data to show that TMVr can be used as salvage therapy in patients with acute torrential MR with underlying HOCM while being supported with ECMO. However, long-term sequelae needs meticulous follow up and prospective studies to establish short and long-term outcomes and safety. This case highlights potential role of TMVr in acute MR settings in the extreme case of profound cardiogenic shock requiring VA-ECMO leading to candidacy for mitral valve replacement in ambulatory setting.
Abstract 12912: Metabolic Labeling of Cardiomyocyte-Derived Small Extracellular-Vesicle (sEV) MiRNAs Identifies MiR-208a in Cardiac Regulation of Lung Gene Expression
Authors: Han Chaoshan , Yang Junjie , Zhang Eric , zhang qinkun , Lal Hind , Krishnamurthy Prasanna , Zhang Jianyi J , Qin Gangjian
Published: June 2023

Background & Hypothesis:
T. gondii
uracil phosphoribosyltransferase (UPRT) can convert 4-thiouracil(4TUc) into 4-thiouridine (4TUd), thus incorporating into nascent RNAs, and the thio-labeled RNAs can be identified by thio-linked-biotinylation and streptavidin-affinity isolation, we hypothesize that cardiomyocyte (CM) expression of UPRT (
CM
UPRT) allows labeling and tracking of CM-derived miRNAs in
PB
sEV and peripheral organs.

Methods & Results:
We generated mice that expressed
T. gondii
UPRT only in cardiomyocytes (
CM
UPRT mice) and tested our hypothesis that CM-derived miRNAs (
CM
miRs) are transferred into remote organs after myocardial infarction (MI) by
PB
sEV. We found that 4TUd was incorporated with high specificity and sensitivity into RNAs isolated from the hearts and
PB
sEV of
CM
UPRT mice six hours after 4TUc injection. In
PB
sEV, 4TUd was incorporated into CM-specific/enriched miRs including miR-208a, but not into miRs with other organ or tissue-type specificities. 4TUd-labeled miR208a was also present in lung tissues, especially lung endothelial cells (ECs), and CM-derived miR-208a (
CM
miR-208a) levels peaked 12 hours after experimentally induced MI in
PB
sEV and 24 hours after MI in the lung. Notably, miR-208a is expressed from intron 29 of α myosin heavy chain (αMHC), but αMHC transcripts were nearly undetectable in the lung. When
PB
sEV from mice that underwent MI (MI-
PB
sEV) or sham surgery (Sham-
PB
sEV) were injected into intact mice, the expression of Tmbim6 and NLK, which are suppressed by miR-208a and cooperatively regulate inflammation via the NF-κB pathway, was lower in the lungs of MI-
PB
sEV-treated animals than the lungs of animals treated with Sham-
PB
sEV or saline. In MI mice, Tmbim6 and NLK were downregulated, whereas endothelial adhesion molecules and pro-inflammatory cells were upregulated in the lung; these changes were significantly attenuated when the mice were treated with miR-208a antagomirs prior to MI surgery.

Conclusion:
CM
UPRT mice enables us to track
PB
sEV-mediated transport of
CM
miRs and identify an miR-208a-mediated mechanism by which myocardial injury alters the expression of genes and inflammatory response in the lung.
Abstract 12927: A Deep Learning Algorithmic Approach to Identify Predictors of In-Hospital Outcomes in Takotsubo Cardiomyopathy
Authors: Sherif Akil A , Mishra Ajay K , Agarwal Siddharth , Titus Anoop , Rajendran Aiswarya , Ramsaran Eddison
Published: June 2023

Introduction:
The use of deep learning (DL) through artificial neural networks is increasingly being employed to analyze large, complex datasets in clinical research allowing for new insights. Takotsubo cardiomyopathy (TTS) has an incidence of 12.4% with a reported in-hospital mortality of 5% in the US. While overall risk factors for the condition have been identified, data regarding in-hospital predictors are scant. We sought to apply a DL Artificial Neural Network (ANN) algorithm to identify predictors of in-hospital mortality in patients with TTS.

Methods:
The National In-patient Sample is the largest, publicly available, repository of in-patient data comprising a 20% stratified sample of all US hospital discharges. We identified all unweighted hospitalizations with a primary diagnosis of TTS from 2016-2019 using International Classification of Diseases, Tenth Revision diagnosis codes. Data regarding demographics, hospital characteristics, known confounders and associated secondary diagnoses were abstracted. These data were then analyzed using a multilayer perceptron ANN where 70% (4,579) of the dataset was used for training and 30% (1,894) for testing. An independent variable importance analysis was also performed.

Results:
The training and testing models were able to accurately predict outcomes in 98.6% and 98.2% of the data, respectively. ANN identified covariates with high independent variable importance (normalized importance of >70%) include interstitial lung disease, ventricular fibrillation, end-stage renal disease, 3rd degree AV block, sudden cardiac arrest, and acute PE (Model AUC: 0.952).

Conclusions:
Deep learning-based algorithms utilizing ANNs have the potential to identify predictors of in-hospital mortality with significant accuracy in large volume databases such as the NIS. Among all the covariates that were analyzed, our model was able to identify covariates associated with high importance in predicting outcomes.
Abstract 12930: Plasma Proteome Distinguishes Adaptive and Maladaptive Signaling in Repaired Tetralogy of Fallot
Authors: Jones Andrea L , Clouthier Katie L , Edwards Jonathan J , Mai Anh Duc , Fazelinia Hossein , Reddy Sushma , Mercer-Rosa Laura M
Published: June 2023

Introduction:
Patients who have undergone tetralogy of Fallot (TOF) repair are subject to chronic volume and/or pressure overload, leading to a 40% probability of right ventricular (RV) failure by the third decade of life. We sought to identify a plasma proteome profile of the systemic response to right heart stress to better understand the mechanisms of RV failure and identify novel RV remodeling biomarkers.

Methods:
Patients with repaired TOF were recruited at the time of standard of care cardiac MRI (CMR) (N=14), and blood samples were collected. Plasma proteomics was assessed using data independent acquisition mass spectrometry. Proteins that were significantly affected between groups were identified and used for pathway enrichment analysis.

Results:
Patients underwent primary TOF repair at median 2.9m (IQR 0.8, 4.1) and CMR at median 16yrs (IQR 15, 18). Patients were grouped based on median indexed RV end diastolic volume (RVEDVi). Group 1: median RVEDVi 146ml/m
2
(IQR 139, 164) (N=9); Group 2: median RVEDVi 114ml/m
2
(IQR 104, 130) (N=5); p<0.001. RV ejection fraction was equal between groups (mean 56% vs. 55%; p=0.68). Forty-one proteins were significantly differentially abundant: 19 enriched in Group 1 and 22 enriched in Group 2 (Fig 1; p<0.05). Adaptive signaling in Group 1 was characterized by upregulation of proteins involved in antioxidant mechanisms (SOD1, TXN, PRDX1&2), calcium handling (S100A6, CALM1), and proteostasis (UBB, HSPA8). Maladaptive signaling was characterized by upregulation of glycolytic pathways (MDH1, PGK1) and heme protein oxidation (ALAD) and downregulation of proteins to counter acute stress (complements, ORM1&2).

Conclusion:
Patients with repaired TOF and moderate-severe RV dilation have a distinct maladaptive plasma proteomic profile independent of ejection fraction. These data suggest that profiling the circulating plasma proteome may be used to monitor disease progression prior to the onset of clinical heart failure.
Abstract 12945: Disparities in the Prevalence of Acute Myocardial Infarction Among Patients With Non-Alcoholic Fatty Liver Disease a Nationwide Database Analysis
Authors: MUNGUTI CYRUS M , Hayat Umar , Okut Hayrettin , Akidiva Samuel , Abukar Abdullah , Shaheen Wassim H
Published: June 2023

Background:
Non-alcoholic liver disease (NAFLD) is among leading causes of chronic liver disease. Recent evidence suggests an association of NAFLD with cardiovascular diseases; however, few studies have analyzed national level database for this relationships. We aimed to assess the trends and predictors of acute myocardial infarction (AMI) among NAFLD patients in the United States.

Methods:
The National Inpatient Sample (NIS) database from 2016 to 2019 was queried using international classification of disease (ICD-10) diagnostic codes to identify patients with primary diagnosis of NAFLD and secondary diagnosis of AMI. Basic demographic variables were analyzed to determine the disparities in prevalence of AMI among NAFLD patients. Univariate logistic regression model was used to compare the odds of development of AMI among NAFLD patients using demographic characteristics. Multivariate logistic regression analysis was done to determine whether NAFLD is an independent predictor of AMI.

Results:
A total of 58,519 patients had a diagnosis of NAFLD and of these, 5,448 had AMI. Of these, 61% were males, 82% were aged 50 years and over, 68% were white, 8% Black, 16% Hispanic, Asian or Pacific Islander. Females were less likely to have AMI [OR 0.46, 95% CI 0.43-0.48]. Patients <50 years with NAFLD were less likely to develop AMI [OR 0.41, 95% CI 0.38-0.44]. Compared to the whites, blacks [OR 0.57, 95% CI 0.51-0.61,
p<
0.001] were less likely to have AMI. However, Hispanics [OR 1.16, 95% CI 1.07-1.25,
p<
0.001] and Asian and Pacific Islanders [OR 1.31, 95% CI 1.13-1.51,
p<
0.001] were more likely to have AMI compared to the whites. On multivariate analysis, NAFLD was found to be an independent predictor of AMI [OR 1.55, 95% CI 1.51-1.60,
p<
0.001] after controlling for sociodemographic variables such as age, sex, race, smoking status, insurance status, hospital location and teaching status, and clinical variables such as previous MI, Congestive heart failure, diabetes mellitus, chronic kidney disease, hyperlipidemia, and hypertension.

Conclusions:
This analysis suggests older white males with NAFLD had a higher prevalence of AMI and that NAFLD is an independent predictor of AMI.
Abstract 12946: L-Arginine Attenuates Myofibroblast Phenoconversion and Fibrosis in the Human Heart
Authors: Varzideh Fahimeh , Jankauskas Stanislovas , Wang Xujun , Mone Pasquale , Lombardi Angela , Santulli Gaetano
Published: June 2023

Introduction.
L-Arginine (L-Arg) is a semi-essential amino acid involved in a number of biological processes. L-Arg has been recently shown to have beneficial effects on functional capacity in heart failure. However, the molecular mechanism underlying these actions are mostly unknown and a potential direct effect of L-Arg on cardiac fibroblasts has never been investigated hitherto. Transforming growth factor (TGF)-β is one of the main profibrotic cytokines, known to activate fibroblasts into myofibroblasts stimulating the production of extracellular matrix (ECM). In fibrosis condition, excessive ECM alters myocardial structure, eventually impairing cardiac function.

Hypothesis.
We hypothesized that L-Arg could mitigate TGF-β-dependent phenoconversion of human cardiac fibroblasts (HCFs).

Methods.
We isolated primary cardiac fibroblasts from human hearts (protocol approved by the Institutional Review Board for protection of human subjects) and tested a model of fibrosis obtained by treatment with TGF-β. Isolated HCFs were characterized by immunostaining. Early passage HCFs were treated with TGF-β or TGF-β + L-Arg at different doses and time points. The mitochondrial generation of reactive oxygen species (ROS) was assessed by MitoSox at the confocal microscopy.

Results.
TGF-β induced a significant upregulation of established markers of myofibroblast activation and fibrosis (including
Fibronectin, Col1A1, Col1A2,
and
Periostin
), which was significantly attenuated by L-Arg, as confirmed by RT-qPCR, immunostaining, and immunoblot. Moreover, we observed that TGF-β treatment significantly increased the mitochondrial generation of ROS, which was again prevented by co-treatment with L-Arg. In addition, L-Arg significantly reduced SMAD-2 protein expression.

Conclusions.
Our findings demonstrate, for the first time to our knowledge, the anti-fibrotic role of L-Arg in HCFs, mediated via a TGF-β/SMAD-2 signaling pathway.
Abstract 12958: The Dark Side of Normal Healing: Fibrous Encasement of a Subcutaneous ICD Coil
Authors: Liu Kevin , Wu Ele , Uzunoglu Ekin , elayi Claude , Catanzaro John
Published: June 2023

Introduction:
Implantable devices elicit fibrotic and inflammatory responses, which may result in reduced efficacy of the device. Prior literature has addressed thrombus formation and fibrous encapsulation of intravascular leads. This mechanism is at least in part different than subcutaneous fibrosis. However, there have been scarce reports of fibrosis related to subcutaneous leads.

Case:
A 74 year-old male with long standing ischemic cardiomyopathy and absence of pacing indication met indications for primary prevention S-ICD. After shared decision making, a device was implanted with defibrillation thresholds at 65 joules. He later presented with interventricular dyssynchrony (QRS 160 msec) and symptomatic heart block. Upgrade to a biventricular defibrillator was undertaken with removal of the S-ICD system. S-ICD coil manual traction failed to free the lead from the subcutaneous space of implantation. After extensive blunt dissection and removal of the coil, extensive coil ingrowth and fibrosis was noted (Figure 1).

Conclusions:
This case describes the occurrence and visually documents extravascular coil fibrosis and ingrowth into the SICD coil, similarly seen in intravascular ICD leads. The S-ICD coil is a necessary component of the shocking vector and extensive fibrosis may contribute to elevated shock impedance and failed defibrillation thresholds. In cases of elevated shock impedance, it is unknown whether failed defibrillation thresholds or elevated high voltage shock impedance is the result of the generator, coil, or both. Further research is warranted to ascertain whether failed defibrillation thresholds and increased shock impedance is due solely from the SICD generator pocket. Advances in coil technology and regenerative medicine may offer insights into mitigation of the inflammatory process.
Abstract 12981: Non-Conventional Causes of ST-Elevation Myocardial Infarction: Essential Thrombocytosis
Authors: Block Cole G , Brownell Kenneth , Kinno Menhel
Published: June 2023

Case:
A 61-year-old female with no significant past medical history, except hospitalization for COVID-19 pneumonia complicated by myocarditis ten months prior, presented to the emergency department with worsening chest pain over the last two weeks. The admission electrocardiogram (ECG) was without ischemic changes. The initial impression was that the patient's symptoms were attributed to her prior myocarditis. However, a repeat ECG obtained six hours later, due to worsening chest pain, demonstrated ST-segment elevations in leads V2, I and AVL. Emergent coronary angiography was performed, showing a 90% occlusion of the proximal LAD, which was managed with a drug-eluting stent. Admission platelet count was significantly elevated at 1,049,000mm
3
, which resulted in a hematology consultation. Her further work up included a positive JAK2-V617F mutation and negative BCR-ABL1 translocation, which confirmed the diagnosis of essential thrombocythemia. During the prior hospitalization for her COVID pneumonia, she underwent invasive coronary angiogram for suspected myocardial infarction in the setting of elevated troponin, which showed a mild, non-obstructive lesion in the proximal LAD. She underwent a cardiac MRI that demonstrated both sub-epicardial and mid-wall late gadolinium enhancement consistent with myocarditis.

Discussion:
Essential thrombocythemia is a clonal myeloproliferative disease caused by a pathological expansion of megakaryocytes, which results in excess platelet production. Essential thrombocythemia leads to a hematologic hyper-viscosity and subsequent increased risk of vasomotor, thrombotic and hemorrhagic manifestations. Myocardial infarction as the primary clinical presentation of essential thrombocythemia is rare but an important risk factor that should be considered in patients presenting with acute coronary syndromes and elevated platelet counts, both with and without traditional cardiovascular risk factors.
Abstract 12985: Extensive Valvular and Mural (Endocardial) Papillary Elastofibromatosis
Authors: Modi Vivek , Gasimli-Gamache Leyla , Elmi Daniel , Longo Santo , Shirani Jamshid
Published: June 2023

Introduction:
Papillary fibroelastomas (PFEs) are benign, often isolated, valvular tumors of endocardial origin although they may originate from non-valvular tissue and can be multiple. We report a unique case of PFE that involved 2 cardiac valves and nearly entire left ventricular (LV) endocardial surface.

Case:
A 73-year-old white woman with a history of non-valvular atrial fibrillation was admitted with intermittent worsening headaches and loss of peripheral vision in the right eye. An occipital-parietal hematoma was detected on brain computed tomography. Transthoracic echocardiogram showed multiple mobile masses on the mitral valve and the subvalvular apparatus. Transesophageal echocardiography showed additional involvement of the aortic valve and LV endocardium and no otherpotential source of embolism. She experienced recurrent systemic embolism and underwent surgery for the removal of cardiac masses. At surgery, more than 40 loosely attached individual and clustered PFEs (some shown in Figures A and B) confirmed by histology (Figure C) covered both aortic (Figure D and E) and mitral (Figure F) valves and nearly the entire LV endocardial surface (including papillary muscles,Figure G). All LV masses were removed and aortic and mitral valves were replaced. Conclusion. Although cases of multiple valvular PFEs have been reported previously, we report a unique case with a large number of PFEs that involved 2 cardiac valves and the entire mural surface of LV. We have used the term papillary elastofibromatosis to describe such an extensive tumor growth.
Abstract 12995: Use of Percutaneous Septal Closure Device for Paradoxical Cerebral Fat Emboli in a Young Female With Patent Foramen Ovale
Authors: Thompson Kevin , Asif Anum , Ahmed Almomani
Published: June 2023

Introduction:
Cerebral fat emboli (CFE) is a rare (0.9-2.2%) and fatal complication (up to 10% mortality) after burst fractures of the long bones. Studies have reported a worse prognosis with the concomitant presence of a patent foramen ovale (PFO) by allowing a portal to reach systemic circulation, which could be preventable with closure devices; however, it remains unexplored.

Clinical Case:
23-year-old female without any medical history, admitted to trauma ICU after a high-energy motor vehicle collision resulting in left femur open fracture, ribs, vertebral fractures, and left-sided pneumothorax. She was intubated due to poor mental status. CT head was unremarkable, but subsequent brain MRI showed multiple punctate foci of hyperintensity in the bilateral white matter of cerebral hemispheres, corpus collosum, cerebellum and brainstem, representing fat embolism
(Figure).
Transthoracic and transesophageal echocardiography confirmed a small PFO. After a multidisciplinary team discussion, PFO closure via Amplatzer device was done to reduce the risk of systemic embolism burden.

Discussion:
In patients with long bone fractures, right-to-left shunts from PFOs have been shown, by transcranial doppler (TCD), to be associated with larger and frequent micro embolic signals (MES) in the brain. TCD has also shown decreased embolic load and significant reductions in the size of emboli that make it to cerebral circulation after successful percutaneous closure of PFOs. Similar results are seen in prospective high-risk long bone fractures before orthopedic interventions. This suggests there could be a potential role of closure devices in such trauma patients with PFO.

Conclusion:
There could be a potential role of closure devices in selected trauma patients with paradoxical cerebral embolism and a PFO, however, the benefits of long-term outcomes need to be explored in larger cohorts.
Abstract 13019: LV Thrombus With Embolic Phenomena: Identifying the Culprit
Authors: Samaan Sara , Moey Melissa , Kreeger Wayne
Published: June 2023

Background:
Left ventricular (LV) thrombus occurs with prior myocardial infarction (MI), particularly anterior ST-elevation MI (STEMI), dilated cardiomyopathy, and prothrombotic conditions.

Case:
A 38-year-old female with poorly controlled type 2 diabetes mellitus presented with leg pain and dyspnea. Her left lower extremity was cold and mottled, with absent pulses in both legs. EKG revealed lateral STEMI. Emergent coronary angiogram revealed 85% proximal left circumflex stenosis and 100% stenosis of the proximal first obtuse marginal branch (not amenable to intervention due to small vessel caliber). The patient then underwent bilateral iliofemoral and popliteal embolectomy. Transthoracic echocardiogram revealed ejection fraction (EF) of 40% and a 1 x 1 cm thrombus attached to the posteromedial papillary muscle; heparin was started. The patient later developed right-sided weakness; brain MRI revealed multiple acute-subacute infarcts in the left cerebral hemisphere. Transesophageal echocardiogram was negative for patent foramen ovale or shunt.

Decision-making:
LV thrombus with embolic phenomena raised suspicion for underlying thrombophilia. The patient was started on warfarin and clopidogrel, with outpatient follow-up for hypercoagulability workup, which was negative. Cardiac MRI later revealed resolution of LV thrombus, and oral anticoagulation was discontinued after 3 months, and switched to aspirin.

Conclusion:
LV thrombus is far more common after anterior STEMI as it affects a larger area of myocardium, but it can also occur with lateral STEMI. Hypercoagulability state should be considered on the differential of LV thrombus in the setting of lateral STEMI. If hypercoagulability workup is negative, aggressive risk factor modification for coronary disease should be pursued.
Abstract 13023: Exercise Training Potentiates Diuretic Benefits on Mechanism of Arterial Pressure Control in Hypertensive Postmenopausal Rats: Role of Inflammatory and Redox Balance
Authors: Ferreira Maycon , Dias Danielle d , Silva Gabriel d , Silva Michel P , Araujo Amanda A , Santos Camila P , Dutra Marina , Bernardes Nathalia , Irigoyen Maria Claudia , de angelis katia
Published: June 2023

Introduction:
Thiazide diuretic is a classic drug used to treat elevated arterial pressure (AP). However, their neuroinflammatory effects are limited when compared with other therapies.

Objective:
To compare the effect of hydrochlorothiazide (HCTZ) alone or combined with concurrent exercise training (aerobic+resistance, CET) on mechanisms of AP control and on inflammatory and redox balance in hypertensive postmenopausal rats.

Methods:
Female spontaneously hypertensive rats were distributed into sedentary (S) and ovariectomized groups: sedentary (OS), sedentary treated with HCTZ (OSH), trained (OT) and trained treated with HCTZ (OTH). HCTZ treatment (30 mg/kg) and CET (40-60% maximal capacity, 3 days/wk) were conducted for 8wks. AP was directly recorded at rest and after vasopressor system blockade (vasopressin antagonist, losartan and hexamethonium). Inflammation and oxidative stress were evaluated in cardiac tissue.

Results:
Trained groups presented higher exercise tests performance. Systolic (OT:178±18 and OTH:178±17 vs. OS:205±15) and mean AP (mmHg) (OTH:153±17 vs. OS:176±16) were reduced in trained groups. CET promoted an increase in both bradycardic and tachycardic responses of baroreflex sensitivity and a reduction in AP variability indexes in relation to OS group. After sympathetic blockade, AP (mmHg) reduction was higher in OS group (-75.7±19.2 vs. S:-53.2±12.6 and OTH:-49.8±12.4). In addition, IL-10 (OTH vs. OS and OSH) and IL-10/TNF-alpha ratio (OTH vs. S, OS, OSH and OT) were higher in OTH group. OS group showed increased NAPDHoxidase and reduced catalase (vs. S); however, these changes were not observed in OTH group. Negative correlation was observed between sympathetic vascular modulation and IL/TNF-alpha ratio (p<0.001, r:-0.6).

Conclusions:
We concluded that CET alone or combined with HCTZ are more efficient approaches than HCTZ to reduce AP and improve AP control of circulation. Specifically, the combination HCTZ plus CET induces additional positive adaptations on physical, autonomic, inflammatory and redox balance. These results highlight the key role of exercise in the management of HTN, probably impacting on the quality of life and reducing the residual risk in post menopause. Grants: FAPESP (2019/06277-0).
Abstract 13027: Reduced Left Atrial Strain is More Common in Embolic Stroke of Undetermined Source Compared to Non-Cardioembolic Stroke and Can Predict Atrial Fibrillation on Outpatient Cardiac Monitoring
Authors: Bashir Zubair , Chen Edward W , Wang Shuyuan , Goldstein Eric D , Rana Maheen , Shu Liqi , Kala Narendra , Dai Xing , Mandel Daniel , Yaghi Shadi , Has Phinnara , Simmons James , Song Christopher , Haines Philip
Published: June 2023

Embolic stroke of undetermined source (ESUS) accounts for 20% of all ischemic strokes with at least 30% having biomarkers of atrial cardiopathy. Traditional parameters of left atrial (LA) structure and function (particularly Left Atrial Volume Index) are similar in ESUS and non-cardioembolic (NCE) stroke subtypes. LA strain measured by speckle tracking echocardiography (STE) is an emerging non-invasive technique to assess LA structure, function, and biomechanics. Our study evaluates whether LA strain differs between patients with ESUS and NCE and whether LA strain magnitude predicts diagnosis of atrial fibrillation (AF) in ESUS.

Hospitalized patients with ESUS and NCE stroke subtypes who underwent in-hospital echocardiography were included. STE was performed, and three phases of LA strain (reservoir, conduit, and contractile) were measured. Binary logistic regression analyses were performed to determine the association between different phases of LA strain and stroke subtypes (ESUS vs NCE) as well as AF detection in ESUS patients.

A total of 685 patients met the inclusion criteria. Mean age was 65 years; 55% were men; 49% of strokes were NCE; and 51% were ESUS. In patients with ESUS, 57% (189/330) underwent cardiac monitoring. AF was detected in 17.4% (33/189). In fully adjusted binary logistic regression analysis, patients with ESUS had lower LA reservoir strain (adjusted OR 0.99, 95% CI 0.98-0.99, p = 0.039) and LA contractile strain (adjusted OR 0.98, 95% CI 0.97-1.00, p = 0.089). Furthermore, lower LA reservoir strain was associated with AF detection in ESUS patients (OR 0.96, 95% CI 0.93-0.99, p = 0.028).

In conclusion, all phases of LA strain were reduced in ESUS compared to NCE. This suggests the presence of atrial cardiopathy in ESUS stroke patients. Furthermore, atrial strain was significantly reduced in ESUS patients found to have AF. These findings may carry mechanistic significance in stroke development and AF detection in ESUS patients.
Abstract 13040: Insulin-Like Growth Factor-1 Upregulates Larp6 via Translational and Post-Translational Mechanisms in Vascular Smooth Muscle Cells, Leading to Elevated Collagen Production
Authors: Danchuk Svitlana W , Delafontaine Patrice , Higashi Yusuke
Published: June 2023

Introduction:
Collagen content in atherosclerotic plaque is a hallmark of plaque stability. We have shown that insulin-like growth factor-1 (IGF1) increased collagen content in atherosclerotic plaques of Apoe
-/-
mice. We have identified LARP6 (La Ribonucleoprotein Domain Family, Member 6), a type I collagen mRNA-binding protein, as a mediator of IGF1-dependent type I collagen upregulation and increased mature fibril formation by smooth muscle cells (SMC), however specific mechanism has not been elucidated yet.

Methods and Results:
Micro-RNAs, including miR-1976 have been shown to bind to LARP6 mRNA. We found that SMC treatment with IGF1 significantly downregulated miR-1976 by 41±5% after 3h (P<0.05), consistent with the IGF1-induced LARP6 upregulation. In fact, miR-1976 mimic (20 nM) decreased LARP6 by 67% (P<0.05) and reduced type I procollagen protein levels by 85% (P<0.05). MiR-1976 mimic inhibits IGF1-induced LARP6 upregulation showing miR-1976 involvement in IGF1 effect on LARP6. It has been reported that LARP6-mediated promotion of procollagen synthesis may be regulated by phosphorylation of LARP6, therefore we investigated whether IGF1 induces LARP6 phosphorylation in cultured human aortic SMCs. For this experiment, SMCs were serum-starved and treated for 0-48h with 10 ng/mL IGF1. LARP6 protein was detected by immunoblots as a single 67kDa band in untreated SMC. However, after 6h of IGF1 treatment there was additional phosphorylated LARP6 band detected at 70 kDa. The levels of 70kDa LARP6 time-dependently increased up to 18h of treatment, with a concomitant increase of type I procollagen and collagen expression levels.

Conclusions:
In summary, our data suggests that (i) IGF1 downregulates miR-1976, thereby increasing LARP6 expression levels and (ii) IGF1 induces phosphorylation of LARP6, thereby promoting LARP6 activity. Our study revealed novel mechanisms underlying IGF1-induced type I collagen upregulation in vascular SMC and potentially in atherosclerotic plaques.
Abstract 13067: Chronic Ischemic Heart Failure Defines Immune Cell Activation Signatures From ScRNA-seq and Flow Cytometry With Implications for Cardiac Resident Cells
Authors: Merten Maximilian , Rasper Tina , Schuhmacher Bianca , Cremer Sebastian , Hoffmann Jedrzej , Zeiher Andreas M , Dimmeler Stefanie , Abplanalp Wesley T
Published: June 2023

Adverse remodelling and sustained inflammation are key features of chronic ischemic Heart Failure (HF) with reduced ejection fraction. The importance and role of monocytes and T cells in early stages after myocardial infarction are known, however their role in progression of chronic HF remains elusive. Single cell RNA sequencing of peripheral immune cells from healthy and HF donors was performed to gain insights into these altered immune profiles, revealing an increase of activated T cells in HF together with an enrichment of antigen presenting molecules (incl. HLA-DRB5) and co-stimulatory molecules (ICAM-1) on antigen presenting cells. Validation via flow cytometry in 55 young healthy controls and 110 HF patients confirmed elevated HLA-DRB5 levels in HF derived monocytes, which was positively correlated with both ICAM-1 and TREM-1 (p=0.0001 for both), indicating T cell activation induction. Accordingly, significant increases in activated CD4+ and CD8+ T cells (p=0.0001 for both) were observed in HF. Also, increasing relative TCR clonality from T cell receptor (TCR) sequencing of HF patients and age matched controls suggests that circulating T cells expanded. Examination of potential downstream effects of the enhanced immune cell activation was done by measuring the serum of HF patients, showing increases in sICAM-1, IL-6 and TNFRI levels (1.75x-, 5.30x-, 2.63x-fold respectively). This secretome of HF patients was applied to endothelial cells to study direct effects, revealing increased adhesion capacity to co-cultured monocytes. Additionally, these HF secretome-exposed endothelial cells had decreased levels of the checkpoint inhibitor PD-L1 which is known to block autoimmune activity by T cells. Taken together, these data suggest HF is associated with enhanced monocyte and T cell activation as well as T cell clonal expansion. These processes may disturb resolution of inflammation in the cardiac tissue and lead to adverse remodelling and cardiac damage. More data are needed to assess the specific role of chronic monocyte and T cell activation in the progression of heart failure.
Abstract 13090: Not Your Simple Swimmer’s Ear: Ramsay Hunt Syndrome Complicated by Gradenigo Syndrome, Varicella Zoster Meningoencephalitis, and Superimposed Bacterial Necrotizing Otitis Externa in a Heart Transplant Patient on Chronic Immunosuppression
Authors: Benavente Kevin , Kozai Landon , Silangcruz Krixie , Rimm Julian , Zhang James , Kim Lisa , Banerjee Dipanjan
Published: June 2023

Introduction:
Orthotopic heart transplantation (OHT) increases the risks of varicella-zoster reactivation, and severe complications may arise due to infection in the setting of active immunosuppression. Complications include meningitis, facial nerve palsy (known as Ramsay Hunt Syndrome), and bacterial superinfection. When severe bacterial ear infections spread to the petrous apex, facial pain accompanied by otitis media and abducens nerve palsy may also occur, classically known as Gradenigo Syndrome.

Case Report:
We present a case of a patient 15 months post OHT who came in with left-sided facial droop and pain, abducens palsy, crusting facial rash, and ear swelling. Imaging revealed necrotizing otitis externa, with associated otitis media, petrous apicitis, and signs suggestive of encephalitis. A viral panel resulted positive for zoster infection, with superimposed methicillin-resistant staphylococcus aureus infection. Despite treatment with antibiotics and antivirals, the patient's mentation declined, with subsequent lumbar puncture revealing zoster meningoencephalitis. The patient’s mycophenolate mofetil (MMF) immunosuppression was suspended, and he was continued solely on therapeutic tacrolimus. His antiviral was switched to intravenous acyclovir and he was continued on six weeks of antibiotic therapy. The patient demonstrated resolution of his acute infection, however he continues to have residual facial and abducens nerve palsies. On discharge, the patient was resumed on MMF without any cardiac complications.

Conclusions:
This is the first documented case of Ramsay Hunt Syndrome, complicated by Gradenigo Syndrome and varicella-zoster virus meningoencephalitis in an OHT recipient. Our patient's immunosuppression level was the most important factor leading to the concurrence of these novel complications. Physicians should consider and assess for symptoms of these potential sequelae in all transplant patients, and carefully manage immunosuppressive agents to allow for resolution of the infection, while avoiding rejection. While residual neurologic deficits may be challenging to manage, this case demonstrated successful treatment of these complications while avoiding significant cardiac sequelae.
Abstract 13106: Prevalence, Characteristics, and Outcomes of Atrial Fibrillation Patients Attended by Emergency Medical Services
Authors: Ball Jocasta , Mahony Emily , Nehme Emily , Nehme Ziad , Stub Dion , Smith Karen
Published: June 2023

Introduction:
Atrial fibrillation (AF) remains the most common sustained cardiac arrythmia and is a growing burden on healthcare resources, despite improvements in prevention and management. AF is a common cause of hospitalisation, and for acute episodes, patients often contact Emergency Medical Services (EMS) for treatment and transport. However, there is a paucity of data describing the burden of AF presentations on EMS.

Aims:
To determine prevalence, characteristics, and outcomes of patients presenting with AF attended by EMS using a large population-based sample.

Methods:
Consecutive EMS attendances for AF in Victoria, Australia from January 2015 to June 2019 were included if patients had a diagnosis of ‘AF’ or ‘arrhythmia’ with AF on electrocardiogram. Data were individually linked to emergency, hospital admission, and mortality records.

Results:
AF was the reason for emergency ambulance attendance in 23,925 of 2,237,145 cases (1.1%). Median (IQR) age was 76 (66,84) years and 57% were female. Eighty-four percent of patients had a high thromboembolic risk (CHA
2
DS
2
-VASc score ≥2), 73% had a heart rate >100bpm, and >50% were normotensive (mean SBP 133 ± 28mmHg). Forty-four percent of patients received no medical intervention by paramedics and 98% were transported to hospital. From the Emergency Department, 19% of patients were discharged home, 36% went to a short-stay unit, 34% were admitted to a general medical ward, and 7% were admitted to a coronary care unit. Median (IQR) length of stay for those admitted was 1 (1,4) day. Of 5,000 cases reattended for AF during the 4.5 year study period, 22% of reattendances occurred within 30 days and 34% within 6 months of the index event. Overall, 22% died during the study period, 37% of those within 6 months of the index event.

Conclusions:
EMS utilisation for acute episodes of AF is common and associated with many reattendances. Further studies are required to investigate novel pathways of care to reduce AF burden on healthcare systems.
Abstract 13119: Local Diastolic Dysfunction is Associated With Decreased Myocardial Viability in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Frljak Sabina , Poglajen Gregor , Cerar Andraz , Zemljic Gregor , Vrtovec Bojan
Published: June 2023

Introduction.
Although impaired global diastolic function is a key determinant of heart failure with preserved ejection fraction (HFpEF), the impact of local diastolic dysfunction is less clear.

Hypothesis.
We analyzed the distribution and myocardial viability correlates of local diastolic dysfunction in patients with HFpEF.

Methods.
We enrolled 30 patients with HFpEF (NYHA class III, LVEF >50%, E/e' >15, and NT-proBNP >300 pg/ml) who were referred to our center for cell transplantation. Before transplantation, all patients underwent electroanatomical mapping; viable myocardium was defined as unipolar voltage (UV) ≥8.27 mV and non-viable myocardium was defined as UV <8.27 mV. Local diastolic function was assessed by a novel algorithm based on the measurement of local mechanical diastolic delay (LMD). At each sampling point, LMD was measured as timing difference between global end diastolic time (based on left ventricular volume) and maximum local diastolic time (based on local wall movement of the mapping point).

Results.
Most of the patients were male (77%), with a mean age of 62±10 years, creatinine of 1.05±0.40 mg/dl, E/e’ of 18.0±3.5, and LVEF of 57.6±6.1%. Using electroanatomical mapping we generated a total of 4820 mapping points in 30 patients. The mean local mechanical diastolic delay was 47±33 msec, and the coefficient of variation was 0.70. The distribution of local mechanical diastolic delay in points with preserved myocardial viability and decreased myocardial viability is presented in Figure 1. We found a significant inverse correlation between UV and LMD (r= -0.18, P=0.001).

Conclusions.
In patients with HFpEF, areas of local diastolic dysfunction are unevenly distributed and appear so correlate with areas of decreased myocardial viability.

Figure 1.
Distribution of LMD in areas of decreased and preserved myocardial viability.