bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12211: Water Hammer Shock Causing Rupture Of Vulnerable Cap Of Culprit Lesions In Acute Coronary Syndrome: An Angiographic And Machine Learning Analysis
Authors: Nguyen Thach N , Ly Vi N , Le Thoa , Nguyen Thu Q , Le Minh Anh , Nguyen Thoai , Ha Dat Q , Le Trang , Le Minh H , Tran Nghi V , Vu Loc , Pham Hung N , Ho Dung T , Cao Thinh , Rigatelli Gianluca , Zuin Marco , Nguyen Thuong Nghia T
Published: April 2022

Introduction:
Acute coronary syndrome (ACS) is caused by rupture of coronary plaques. What triggers these ruptures?

Hypothesis:
In the field of hydraulics, in a setting of a tank and draining pipe, if the valve at the distal end of the pipe is open, the fluid flows normally. If the valve closes abruptly, the flow next to the valve stops. However the fluid from the tank continues to flow forward and can collide with the distal stationary fluid. This is called water hammer shock. Could the same event happen in coronary arteries? The contraction of the left ventricle (LV) is similar to the abrupt closure of a valve, stopping the myocardial capillary flow. Could the systolic LV contraction trigger water hammer shock?

Methods:
Angiograms with culprit lesions of ACS (recorded at 15 images/second or 0.06 second per image) were reviewed. The first image was of the artery completely filled with contrast. The subsequent images showed the blood in white color blood moving in over a background of black contrast. The normal flow was laminar. When there was retrograde on top of turbulent flow, this was evidence of a collision between antegrade and retrograde flow (or water hammer shock). The measurements by visual angiographic evaluation and by Machine Learning (ML) included (1) the duration and (2) size of coronary segment with turbulence. The ML program had 2 models (build on Python). Model 1 was built based on U-net and Densenet-121 for vessel segmentation. Model 2 was used for classification of flow. The model 2 was trained based on the convolutional neural network.

Results:
Angiograms of 20 ACS patients showed laminar flow (90%) in diastole. The flow became turbulent during systole with retrograde flow. The area of collision or water hammer shock showed diffuse coarse mixing of black (contrast) and white (blood). The presence of turbulence matched the location of 85% of ruptured plaques. The duration of turbulence lasted 80% of systole. Special protocols were used successfully to train AI to recognize the lesions, retrograde and turbulent flow.

Conclusions:
With the new angiographic technique, detailed images of water hammer shock matched the location of ruptured plaques in ACS patients. These results may help to understand the genesis and offer precise prevention and treatment for ACS
Abstract 12221: Reduction of Inappropriate Shocks Over Time in Hypertrophic Cardiomyopathy Patients With Subcutaneous Implantable Cardioverter-Defibrillators
Authors: Narayanan Chockalingam , Gionfriddo William , Shrestha Srijan , Koethe Benjamin , Katcher Benjamin , Garlitski Ann , Weinstock Jonathan , Homoud Munther , Maron Barry , Maron Martin S , Rowin Ethan J , Madias Christopher
Published: April 2022

Introduction:
Subcutaneous implantable cardioverter defibrillators (SICD) are an attractive option for sudden death (SCD) prevention in younger hypertrophic cardiomyopathy (HCM) patients. Conversely, SICDs have higher rate of inappropriate shock (IAS) when compared to transvenous devices.

Objective:
We characterize incidence of appropriate shock (AS) and IAS and analyze predictors of IAS in HCM SICD patients.

Methods:
Data was collected from HCM SICD patients from 2013 to 2021. We used multivariable logistic regression to assess for predictors of IAS in patients with > 6 mo follow up.

Results:
94 HCM patients (age 47 ± 15 years) underwent SICD implant with mean follow up of 3.7 ± 2.0 year. Maximal LV thickness 20.5 ± 5.8 mm with massive hypertrophy (> 30 mm) in 10 patients (11.8%). Initial DFT with 65J was successful in 88 patients, with 5 more successful after device adjustment. 5 patients (5.9%) had 10 AS (3.2 AS per 100 pt-years). 10 patients (11.8%) had 19 IAS (6.0 IAS per 100 pt-years) due to T wave oversensing (n = 13), P wave oversensing (n = 2), atrial arrhythmia (n=2), and external noise (n = 1). IAS rate decreased over time, with IAS occurring in 8 patients of the initial half of the cohort and in only 2 of the second half. Time to IAS from implant was 11 ± 10.8 mo. QRS duration (OR 1.025, 95% CI 0.997-1.053; P = 0.084) showed trend to prediction of IAS, but no characteristic proved independently significant.

Conclusions:
This data adds to increasing evidence that in high-risk HCM patients, SICD represents a reliable treatment option for SCD prevention. IAS mainly due to cardiac oversensing, was seen in 11.8% of patients within this HCM cohort. IAS decreased over time, possibly due to improved patient selection, implant technique and device programming (SMART pass filter). A larger dataset is likely necessary to better understand this trend.
Abstract 12238: Pressure Overload-Induced Impairment in Gut Wall Permeability Exacerbates Cardiac Dysfunction in IL10 KO Mice
Authors: Goswami Sumanta , Ranjan Prabhat , Roshan Dutta , Prasad Ram , zhang qinkun , Lal Hind , Verma Suresh K
Published: April 2022

Introduction:
Heart failure is the leading cause of morbidity and mortality in the USA. Recently, impaired intestinal permeability is known to augment cardiac dysfunction. Though the cardioprotective role of IL10 is well known, its role in reducing gut dysbiosis and maintaining intestinal permeability during hypertrophic heart failure is not known.

Hypothesis:
We hypothesized that IL10 maintains intestinal permeability and inhibits the release of gut microbial peptides (GMPs) which ultimately improves cardiac function.

Methods:
WT & IL10KO mice were subjected to TAC or sham surgery. Heart and intestine were collected to evaluate inflammation genes expression, immune cell infiltration (flow cytometry), and intestinal permeability (WB and immunohistochemistry). Blood was collected to quantify peptidoglycan (PGN) and other bacterial metabolites (TMAO) levels. The effect of PGN on mitochondrial functions was evaluated in neonatal cardiomyocytes.

Results:
Cardiac functions were significantly reduced in IL10KO mice following TAC. IL10 KO mice showed exacerbated inflammation (IL1β, IL6 and TNFα genes expression) following TAC. TAC induced leukocytes (monocyte/macrophage, T-cell and neutrophils) recruitments in the intestine in IL10KO mice. TAC mice showed gut dysbiosis (16S rRNA sequencing) in IL10KO mice. Further, IL10KO mice exhibited higher intestinal permeability as shown by increase in PV1 level and reduction in zonulin-1 (ZO-1) protein. Plasma PGN level was significantly increased in IL10KO mice following TAC. Pathway-based cardiotoxicity array showed a significant increase in uncoupler protein 2 (UCP2) and phospholamban (PLN; a calcium handling protein) gene expression in cardiomyocytes following PGN treatment. Finally, IL10 treatment restores PGN-induced decrease in mitochondrial membrane potential (TMRE assay) in cardiomyocytes.

Conclusions:
Taken together, data suggest that IL-10 helps to maintain gut wall permeability and reduced gut microbial peptide circulation to the heart and thus improves cardiac function by improving mitochondrial function. Ongoing investigations using molecular approaches will provide a better understanding of gut-heart signaling and its impact on the progress of heart failure.
Abstract 12239: Improvement in Measures of Disease Progression With Tafamidis in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT)
Authors: Hanna Mazen A , Fine Nowell , Gundapaneni Balarama , Sultan Marla B , Witteles Ronald
Published: April 2022

Introduction:
Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) experience a progressive decline in health and quality of life. Tafamidis is an effective treatment for patients with ATTR-CM, and was shown to reduce mortality and CV-related hospitalization in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). As ATTR-CM is a progressive disease, either stabilization or improvement signifies an efficacious treatment.

Methods:
This was a post-hoc analysis of the proportion of patients in ATTR-ACT who stabilized or improved in clinical parameters. In ATTR-ACT, 441 adult patients with ATTR-CM (variant or wild-type) were randomized (2:1:2) to tafamidis 80 mg, tafamidis 20 mg, or placebo for 30 months, with pooled tafamidis (n=264) compared with placebo (n=177). Change from baseline was assessed at each study visit to determine patients who improved/did not change in: 6MWT distance; KCCQ-OS score; NT-proBNP concentration; PGA scale; and NYHA class. Any patient with missing data was considered not improved.

Results:
A significantly greater proportion of patients improved/did not change with tafamidis compared with placebo for each outcome at Month 30 (
Table
). Of patients who started treatment with tafamidis, 20-27% improved in 6MWT distance, KCCQ-OS score, and NT-proBNP concentration at Month 30, compared with 5-10% of patients with placebo. There were greater proportions who improved in these measures at earlier timepoints (32-42% with tafamidis vs 19-24% with placebo at Month 12;
P
<0.01 for all).

Conclusions:
While patients with ATTR-CM are expected to experience a progressive decline over time, a significant proportion of tafamidis-treated patients in ATTR-ACT had improvements in measures of functional capacity, health-related quality of life, and cardiac biomarkers within 12 months and through the study. These data provide further evidence of the clinical benefits with tafamidis in patients with ATTR-CM.
Abstract 12248: Dosing of Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation and Renal Dysfunction
Authors: Rymer Jennifer A , Webb Laura E , Wang Tracy Y
Published: April 2022

Introduction:
Reduced doses of direct oral anticoagulants (DOACs) are approved to prevent bleeding complications in specified populations of patients with non-valvular atrial fibrillation (NVAF). Little is known about the accuracy of DOAC dosing in patients with renal dysfunction.

Hypothesis:
We hypothesized that NVAF patients with renal dysfunction would be more likely to receive an inappropriate dose of a DOAC compared with patients with normal renal function.

Methods:
We examined all patients who had at least two claims for NVAF between 2015 and 2017 in the Symphony Health claims dataset. We defined under-dosing as patients treated with a reduced dose without meeting label specified criteria for dose reduction, and excess dosing as patients treated with a full dose despite meeting criteria for dose reduction. We performed a logistic regression model to measure the effect of CrCl on DOAC dosing.

Results:
Among 86,919 patients with NVAF and CHA
2
DS
2
-VASc
>
2, 12.3% were underdosed and 5.0% were excess dosed. Patients who received excess-dosed or under-dosed DOACs were older and more likely to have comorbidities such as heart failure or history of prior stroke (all p<0.001), compared with patients who were appropriately dosed. Among patients with CrCl > 60 ml/min, under-dosing occurred in 9% of patients, highest among patients treated with edoxaban (18%) and rivaroxaban (10.4%). Under-dosing rates were higher among patients with CrCl 30-59 ml/min, especially for apixaban and dabigatran (
Table)
. Excess dosing occurred in approximately 1 in 5 patients with CrCl <30 ml/min. For every 10 unit decrease in CrCl, the odds of the patient receiving an inappropriately dosed DOAC increased by 27%.

Conclusions:
Incorrect DOAC dosing was observed in a substantial number of patients with NVAF in this large national study. Dosing errors occurred more frequently in patients with lower renal function, suggesting the need for efforts to improve effective and safe dosing of DOACs.
Abstract 12251: Speckle Tracking Echocardiography Changes in Patients Who Developed Atrial Fibrillation Post Coronary Artery Bypass Grafting
Authors: Mannumbeth Renjithlal Sarath Lal , Barssoum Kiro , Chowdhury Medhat , Hassib Mohab , Shankar Abhijeeth , Biswas Suman , Kumar Ashish , Victor Varun
Published: April 2022

Introduction:
Postoperative atrial fibrillation (POAF) is seen in around 30% of patients after coronary artery bypass grafting (CABG). It is associated with increased risk for stroke, heart failure, in-hospital mortality and hospital readmission. Prediction of POAF could help institute preventive and early treatment strategies.

Methods:
We queried PubMed, Ovid Medline, and Cochrane databases for key words ‘atrial speckle tracking” and/or “reservoir strain” and/or “post-operative atrial fibrillation”. We included studies that included patients in normal sinus rhythm before CABG and compared reservoir strain and/or peak atrial longitudinal strain (PALS) between patients who developed POAF and those who did not. Continuous data (LA strain) was pooled as a mean difference comparing patients who developed POAF versus patients who did not. We used the inverse variance method with the Restricted Maximum likelihood estimator of Tau2, for random effect analysis. We used Q and I2 statistics to calculate the heterogeneity.

Results:
Six observational studies met our inclusion criteria with a total of 338 patients, of which 91 patients developed POAF. Left atrial reservoir strain was significantly reduced in patients who developed POAF as compared with those who did not develop POAF, mean difference(MD), 95% confidence interval(CI): -13.97(-15.00-12.93), I2= 53%, , P <0.00001, Figure 1.

Conclusions:
Atrial reservoir strain was significantly reduced in patients who developed POAF as compared to those who remained in sinus rhythm. Atrial reservoir strain can be potentially used to identify patients at risk of POAF. More data is needed for further validation of this finding.

.
Abstract 12254: Predictors of Transthoracic Impedance in Patients Undergoing Electrical Cardioversion
Authors: Redel-Traub Gabriel N , Sudesh Saurabh , Ehlert Frederick , Dizon Jose , Biviano Angelo B , Garan Hasan , Yarmohammadi Hirad
Published: April 2022

Introduction:
Successful synchronized direct current cardioversion (DCCV) requires adequate current delivery to the heart. However, adequate current for successful DCCV is not yet established. Trans-myocardial current depends on two factors: input energy and transthoracic impedance (TTI). While factors affecting TTI have been studied in animal models, factors affecting TTI in humans have not been well established. Here we explored potential factors that affect TTI in humans.

Methods:
Retrospective review of consecutive patients undergoing DCCV at a large quaternary medical center between October 2019 and December 2020 was conducted. Pertinent clinical information, including demographics, echocardiography findings, laboratory findings and body characteristics were collected. Cardioversion details including joules delivered and TTI were recorded by the defibrillator for each patient’s first shock. Predictors of thoracic impedance were assessed using multivariable regression analysis after adjustment for confounders.

Results:
A total of 180 patients were analyzed, 31% of which were female. Mean impedance was 73.15 ± 21.50 (range 39-208). In multivariate analysis, higher TTI was significantly associated with higher BMI (p<0.001,
Figure
) and female gender (p=0.006) after adjustment for all confounders. Other factors including age, history of cardiac surgery, left ventricular ejection fraction, left atrial size, brain natriuretic peptide, and antero-posterior chest diameter were not associated with TTI.

Conclusion:
Our results align with prior studies that body habitus and gender affect TTI and suggest that adjustments in input energy based on these factors may be required for appropriate trans-myocardial current delivery in synchronized cardioversion.
Abstract 12261: Access to Care among Hispanic Patients Hospitalized for Lower Extremity Peripheral Artery Disease
Authors: Harris Kristie M , Luna Paulina , Castro-Dominguez Yulanka , Severiche Carolina , Smolderen Kim G , Mena-hurtado Carlos
Published: April 2022

Introduction:
Compared to other racial/ethnic groups, Hispanics are less likely to access regular primary care, which can delay detection and management of PAD. It is unknown whether in admissions for PAD, a trend towards more burden is observed for Hispanic vs. non-Hispanic White (NHW) patients. We therefore examined emergency department (ED) and elective admissions, length of stay (LOS), and costs accrued by ethnicity in patients hospitalized for primary PAD.

Methods:
The 2011-2017 National Inpatient Sample data were used to identify admissions in Hispanics and NHWs and whether the patient sought care via the ED and if the admission was elective. Yearly and overall percentages for each were determined, and temporal trends evaluated with the Cochran-Mantel-Haenszel test, stratified by ethnicity. Differences in median LOS and cost by ethnicity were evaluated with the Wilcoxon rank sum test.

Results:
From 2011-2017, there were 1,018,220 PAD hospitalizations (39% female, 14% Hispanic) and the percentage of patients who accessed inpatient care via the ED increased in Hispanics and NHWs, but was consistently higher in Hispanics (Fig. 1, all P
trend
<0.0001). Across all years, 58.0% (82,047 of 141,551) of admissions in Hispanics were via the ED compared to 36.7% (321,932 of 876,669) in NHWs (
d
=0.48) and elective admissions were higher in NHWs (396,294; 45.2%) than in Hispanics (38,661; 27.3%,
d
=0.43). Median LOS (4.5 vs. 3.7 days) and cost ($63,813 vs. $52,368) were higher in Hispanics than NHWs (
p
<.0001).

Conclusions:
Hispanic patients are more likely than NHWs to seek emergent, non-elective inpatient PAD care and to be admitted for longer and accrue greater costs. They are also increasingly more likely to access this care via the ED which may provide fewer barriers than other settings, especially for uninsured patients or those without legal immigration status. More accessible outpatient care may potentially reduce ED burden and improve PAD management for this population.
Abstract 12265: The Impact of Gestational Age on the Neonatal Electrocardiogram
Authors: Hartmann Joachim , Paerregaard Maria Munk , Norsk Jakob , Pietersen Adrian , Iversen Kasper , Bundgaard Henning , Christensen Alex H
Published: April 2022

Objective:
The interpretation of the neonatal electrocardiogram (ECG) is challenging and reflects the underlying developing physiology. The possible effects of gestational age (GA) on the ECG has never been evaluated in a large general population study. We aimed at investigating the effect of GA on neonatal electrocardiographic parameters and create GA-specific reference values.

Methods:
The Copenhagen Baby Heart Study is a prospective, general population study that offered cardiac evaluation of neonates. ECGs and echocardiograms were obtained and systematically analyzed. GA, weight, height, and other baseline variables were registered.

Results:
We included 16,462 neonates (52% boys) with normal echocardiograms. Median postnatal age was 11 days (range 0-30 days) and median GA was 281 days (range 238-301 days). Analyzing the ECG parameters as a function of GA we found a significant effect of GA on heart rate (HR), PR-, QRS-, and QT intervals, QRS axis, and maximum amplitudes of R-waves in V1/V6 and maximum S-wave in V6 (all p<0.01). The largest percentual effect of GA was on HR, QRS axis, and R-wave in V1. Boys had longer PR- and QRS intervals and more right-shifted QRS axis within multiple GA-intervals (all p<0.01, Figure:
Box plots of ECG parameters subdivided by gestational age intervals and sex
). The effect of GA generally persisted after adjustment for HR, weight, postnatal age, and sex. In addition, when comparing HR, PR interval, QRS axis, QRS duration, uncorrected QT interval, and QTcBazett subdivided into postnatal age intervals, we found a significant effect of gestational age on most ECG parameters within these postnatal age intervals.

Conclusion:
Gestational age was associated with significant differences in multiple neonatal ECG parameters and the effect generally persisted after multifactorial adjustment. Our results indicate a direct effect of GA on the developing neonatal cardiac conduction system. Use of GA-specific reference values may be useful.
Abstract 12266: Endothelial Cells Senescence Exacerbates Pulmonary Hypertension Through Notch-Induced Pulmonary Arterial Smooth Muscle Cells Proliferation and Migration
Authors: Ramadhiani Risa , Ikeda Koji , Miyagawa Kazuya , Ryanto Gusty Rizky Teguh , Tamada Naoki , Suzuki Yoko , Hirata Ken-Ichi , Emoto Noriaki
Published: April 2022

Background:
Endothelial cell (EC) dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) by mediating structural changes in vasculatures. Various stress that promotes EC dysfunction also induces premature senescence in EC; however, the role of EC senescence in the development of PAH remains unknown.

Hypothesis:
We hypothesized that senescent ECs play a significant role in the development of PAH.

Methods:
We generated EC-specific progeroid mice that overexpress the dominant-negative form of telomere repeat binding factor 2 under the control of the VE-cadherin promoter. Following chronic hypoxia exposure, PH phenotypes were assessed by RVSP and lung histology. Gene expression was assessed by RT-qPCR. The interaction of pulmonary artery ECs (PAECs) and pulmonary artery smooth muscle cells (PASMCs) was analyzed using indirect and direct co-culture systems. In addition, gamma-secretase inhibitor (DAPT) was used to inhibit Notch signaling both in the in-vitro and in-vivo studies.

Results:
The transgene expression was specifically expressed and fairly distributed in various pulmonary blood vessels in EC-specific progeroid mice. After three weeks of hypoxia exposure, EC-specific progeroid mice exhibited exacerbated pulmonary hypertension (PH) phenotype, accompanied by the prominent medial thickening and enhanced proliferation capacity of SMCs in the distal pulmonary arteries. Interestingly, contact-mediated interaction with senescent ECs increased proliferation and migration capacities in SMCs, while the absence of EC-SMC contact abolished those effects. Mechanistically, senescent ECs expressed higher Notch ligands than in young ECs, leading to the enhanced Notch signaling in PASMCs. Consistently, pharmacological inhibition of Notch signaling attenuated senescent ECs’ effects on SMCs in vitro and the PH phenotype in EC-specific progeroid mice in vivo.

Conclusions:
These findings established the critical roles of senescent ECs in the PAH pathogenesis, suggesting a novel pathological-targeted therapeutic approach for PAH.
Abstract 12268: Overexpression of Endothelial p25 Causes Vascular Remodeling by Inducing Premature Aging
Authors: Mondaca Ruff David , Konja Daniels , Singh Sandeep , Wang Yu
Published: April 2022

Introduction:
Cardiovascular diseases are the leading cause of disability and death worldwide. The cyclin-dependent kinase 5 (CDK5) signaling pathway has been implicated in the regulation of SIRT1, a mammalian longevity regulator involved in the cellular homeostasis and aging. However, the participation of p25, the regulatory subunit of CDK5 in cardiovascular diseases has not been fully understood.

Hypothesis:
Selective overexpression of p25 in the vascular endothelium leads to vascular remodeling by accelerating vascular aging.

Methods:
A transgenic mouse model with selective overexpression of p25 in endothelial cells (EC-p25) was established. Aortas were collected from 12- or 30-weeks old EC-p25 and control mice. Vascular tone response, vascular senescence, aortic stiffness and aortic wall hypertrophy were evaluated with wire myography, senescence-associated β-galactosidase (SA-β-gal), alizarin red and heamatoxylin-eosine staining respectively. Protein levels were measured by Western blotting. Primary porcine aortic endothelial cells (PAECs) were transfected with p25, Sirt1 and Sirt1 lacking deacetylase activity, cell death and senescence were evaluated. Sirt1 activity was measured in EC-p25 and Control mice. A p-value p<0.05 was considered as statistically significant.

Results:
Young EC-p25 mice exhibited increased vascular tone compared to the control mice. Alizarin red staining was more abundant in the aorta of 30 weeks old EC-p25 compared with the control mice, whereas SA-β-gal staining and aortic wall thickness were increased in EC-p25 mice. Overexpression of p25 in PAECs induced endothelial senescence and cell death. EC-p25 mice showed increased Sirt1 activity levels. Western blot analysis demonstrated that SIRT1 protein was fragmented in aorta of EC-p25 mice with increased levels of shorter fragments of Sirt1. PAECs transfected with Sirt1 mutant exhibited increased senescence.

Conclusion:
Selective overexpression of p25 in the vascular endothelium may regulate vascular remodeling by increasing vascular tone, vascular and endothelial senescence, aortic stiffness and aortic wall hypertrophy possible by modulating Sirt1 activity and integrity in the aorta of EC-p25 mice, accelerating premature vascular aging.
Abstract 12269: Investigating Arrhythmogenic Potential of a Novel KCNH2 Mutation Leading to Long QT Syndrome
Authors: Tsevi Bright , Akwaboah Akwasi D , Treat Jacqueline A , Goodrow Robert , Lam Victoria , Owusu-Mensah Anthony , Audette Michel , Cordeiro Jonathan M , Deo Makarand
Published: April 2022

Background:
Mutations in the gene KCNH2 have been associated with both Short and Long QT syndrome. In this study, we identified a 1-day old infant that exhibited T-wave alternans coupled with Long QT Syndrome leading to aborted sudden infant death.

Methods:
Genetic analysis of the patient revealed a mutation in KCNH2 resulting in a proline to leucine substitution at position 632 (P632L). Functional electrophysiological studies were performed with the hERG mutation transiently transfected into either Human Embryonic Kidney (HEK) cells or human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The functional effects of P632L were incorporated into biophysical computational models of hiPSC-CM as well as adult human cardiomyocytes to further assess its arrhythmogenic potential.

Results:
The male infant displayed multiple repolarization disorders including T-wave alternans and a QTc =510 ms that appeared 1 day after birth. Genetic screening revealed a heterozygous missense mutation (P632L) in KCNH2 in the infant. Patch clamp analysis of HEK cells transiently transfected with P632L mutation showed a complete loss of function of HERG current compared to WT HERG. Transient transfection of P632L into WT hiPSC myocytes resulted in prolongation of the hiPSC action potential compared to untransfected hiPSC myocytes. Co-transfection of WT and non-functional P632L channels into HEK cells resulted in a dramatic loss of current suggesting a dominant negative effect. Implementing the effects of a complete block of HERG current in the hiPSC-CM computer model prolonged the action potential by 45% and depolarized the resting membrane potentials. In adult human myocyte models, the effects of HERG blockade were more severe in Purkinje cells than that in ventricular myocytes (71% vs. 16% APD prolongation, respectively).

Conclusions:
The mutation P632L causes a complete loss of HERG current and results in QT prolongation. Numerical simulations suggest a more severe phenotype in Purkinje cells than in ventricular myocytes which could be proarrhythmic.
Abstract 12279: CD40, a Significant Mediator of Hypertensive Renal Injury, Activates Pro-Apoptotic P53 Signaling in Human Renal Proximal Tubule Cells
Authors: Zhang Shungang , Breidenbach Joshua , Fahoury Alan , Kleinhenz Andrew , Malhotra Deepak , Dworkin Lance , Kennedy David J , Haller Steven
Published: April 2022

Background:
We have shown clinical evidence that circulating levels of the proinflammatory receptor CD40 contribute to the progression of hypertensive renal disease and that the ligand for CD40 (sCD40L) is significantly elevated in these patients. Experimentally, we developed a CD40 knockout (CD40KO) rat model on the Dahl-S background that is prone to hypertensive renal injury, and demonstrated significantly reduced renal inflammation and proteinuria following high salt diet in the CD40KO vs Dahl-S controls. On this background we used HK-2 cells and created a stable CD40 knockout cell line (HK-2CD40KO) and performed the following experiments.

Hypothesis:
Renal proximal tubule-specific CD40 signaling significantly contributes to the development of renal injury.

Methods:
HK2 cells and HK2-CD40KO cells were stimulated with 100 ng/ml of soluble CD40 ligand (sCD40L) for 24hrs. RNA from duplicate samples was isolated for RNA sequencing followed by bioinformatic pathway analysis (R program). Additionally, one-week high salt diet (2% NaCl) was administered to seven-week old Dahl S wild-type and Dahl S CD40KO male rats (n=8 per group) and kidney cell apoptosis was evaluated by TUNEL staining.

Results:
Bioinformatic analysis identified 1231 differentially expressed genes when comparing sCD40L-stimulated HK2 vs HK2-CD40KO cells. KEGG pathway analysis demonstrated p53 signaling as one of the most significantly altered pathways. The pro-apoptotic gene PMAIP1 was found to be among the most highly upregulated in sCD40L treated HK2 cells vs HK2 control (2.6-fold change), which was confirmed by qPCR and Western blot. Furthermore, CD40KO rats demonstrated significantly reduced renal cell death (3-fold decrease vs. S rat, p<0.01) compared to wild-type Dahl S rats following high salt diet.

Conclusion:
RNA sequence analysis demonstrates that disruption of CD40 in renal proximal tubule epithelial cells significantly alters p53 signaling pathways and the pro-apoptotic gene PMAIP1 is upregulated upon sCD40L treatment. Disruption of CD40 significantly attenuates kidney cell death following high salt diet induced renal injury. Our data indicates that PMAIP1 contributes to CD40-mediated renal injury.
Abstract 12288: Three-Dimensional Location and Heatmap Distribution of Frame Fractures on the GORE Cardioform ASD Device
Authors: Morgan Gareth J , Rodriguez Franco Salvador A , Leahy Ryan , Randall Jess , Zablah Jenny E
Published: April 2022

Objective:
To evaluate the frequency and characteristics of Gore Cardioform ASD Device Frame Fractures (FF) and explore potential associations in patient and procedural practice variables.

Background:
The latest device approved by the FDA for atrial septal defect (ASD) closure is the GORE® Cardioform ASD occluder (GCA). Despite a very low incidence of complications having a direct impact on patient wellbeing, a significant amount of FFs have been observed in the GCA at short to medium-term follow-up, being described in almost one-third of the devices implanted during clinical trials.

Methods:
We performed a retrospective single-center chart review of 54 patients who received a GCA between January 2017 and December 2019, and selected 35 patients in whom a 6-month fluoroscopic follow-up was performed. We evaluated the number and type of fractures based on this fluoroscopic assessment and devised a simple nomenclature system based on three-dimensional (3D) reconstruction of the device's fluoroscopic images. We also evaluated the association between the position and number of fractures, and patient and procedural characteristics.

Results:
The FF incidence in our population was 42.9% at a 6-month follow-up. The factors statistically associated with FF were the size of the defect and the size of the device implanted. FFs were most frequently located in a central position in the right atrial disc. By 3D evaluation, the most common anatomical position for fractures was the anteroinferior quadrant of the right atrial disc. At the time of manuscript submission, no echocardiographic or clinical sequelae were noted in our population.

Conclusions:
The incidence of frame fractures in our population was higher than that observed in published literature, albeit using more intense image scrutiny than that required by other cited studies. We noted that the central portion of the anteroinferior quadrant of the right atrial disc was the most susceptible to FF and found that the defect size and the device size were the only statistically associated factors.
Abstract 12292: Trends and Outcomes of Cardiac Transplantation in the Lowest Urgency Candidates
Authors: Fuery Michael , Chouairi Fouad , Natov Peter , Bhinder Jasjit , Chiravuri Maya , Wilson Lynn , Clark Katherine , Reinhardt Samuel , Mullan Clancy , Miller Elliott , Rogers Joseph G , Patel Chetan B , Sen Sounok , Geirsson Arnar , Anwer Muhammad , Desai Nihar R , Ahmad Tariq
Published: April 2022

Introduction:
Due to discrepancies between donor supply and recipient demand, the cardiac transplantation process aims to prioritize the most medically urgent patients. It remains unknown how recipients with the lowest medical urgency compare to others in the allocation process.

Methods:
We performed a retrospective analysis of the United Network for Organ Sharing database. Patients listed for cardiac transplantation between January 2011 to May 2020 were stratified according to status at time of transplantation. Baseline recipient and donor characteristics, waitlist survival, and post-transplantation outcomes were compared between lower urgency listing and higher urgency listing in the years before and after the 2018 allocation system change.

Results:
Lower urgency patients in the old system were older (58.5 vs. 56 years) and more likely female (54.4% vs. 23.8%) compared to the highest urgency patients, and these trends persisted in the new system for the lowest urgency patients (59 vs. 55 years; 47.0% vs. 23.9% female; p<0.001, all). Donors for the lowest urgency patients were more likely older, female, or have a history of CMV, hepatitis C, or diabetes (p<0.01, all). The lowest urgency patients had longer waitlist times, and under the new allocation system these patients received organs from shorter distances and with decreased ischemic times (178 vs. 269 miles, 3.1 vs 3.5 hours; p<0,001, all). There was no difference in post-transplantation survival (p<0.01, all).

Conclusions:
Cardiac transplantation for lower urgency patients has not been well characterized. Our analysis demonstrates that, over the last decade, these patients receive hearts from donors with additional comorbidities compared to higher urgency patients but that outcomes are similar at one year. Our results may support the utility of early listing and less stringent thresholds for organ acceptance to increase access to cardiac transplantation.
Abstract 12293: Intercalated Disk Nanostructure and Molecular Organization Underlie Conduction Differences Between Atria and Ventricles
Authors: Struckman Heather L , Moise Nicolae , Dunlap Izabella , Chen Zhenhui , Weinberg Seth , Veeraraghavan Rengasayee
Published: April 2022

The intercalated disc (ID) is a complex, heterogeneous structure that affords electrical (gap junctions; GJ) and mechanical (adherence junctions [AJ], desmosomes [Des]) coupling between cardiomyocytes. Electrogenic proteins underlying the action potential upstroke (cardiac sodium channels [Na
V
1.5], inward-rectifier potassium channels [K
ir
2.1] and sodium potassium ATPase [NKA]) enriched within ID nanodomains are emerging as vital machinery for cardiac impulse propagation. ID structure is thus a critical determinant of cardiac conduction. We used indirect correlative light and electron microscopy (
iCLEM
) to assess ID ultrastructure (transmission electron microscopy; TEM) and molecular organization (confocal, STORM super resolution microscopy) in mouse atria and ventricles. TEM uncovered structural differences between atrial and ventricular IDs from the micro- through nano-scales including key factors that may underlie faster atrial conduction: larger interplicate regions and more numerous GJs with associated perinexi. Confocal microscopy revealed significant ID enrichment of Na
V
1.5, K
ir
2.1 and NKA in both atrial and ventricular myocytes. All three displayed more intense immunosignals in atrial myocytes, suggestive of greater expression relative to ventricle. STORM defined the distribution of Na
V
1.5, K
ir
2.1, NKA within the ID relative to AJ, Des, and GJ: In the ventricle, Na
V
1.5 associated most closely with GJ (median intercluster distance: 110 nm), K
ir
2.1 with Des (163 nm), and NKA with both GJ (150 nm) and AJ (135 nm). Next, the % of each electrogenic protein localized within 100 nm from AJ, Des, and GJ were calculated: 47% of Na
V
1.5 around GJs, 35% of K
ir
2.1 around Des and 36% and 39% of NKA near GJ and AJ respectively were the most prominent subpopulations. Protein organization within atria ID was broadly similar with some notable differences: Na
V
1.5 was shifted closer to MJs relative to GJs with K
ir
2.1 showing the opposite pattern. These data provide the first ever comprehensive quantitative picture of ID structure and molecular organization. We are now incorporating these data into our recently published modeling pipeline to generate realistic 3D finite-element meshes of IDs to uncover the structural underpinnings of conduction.
Abstract 12294: Cardiothoracic Surgery Research Articles Supported by National Institutes of Health Grant Funding Exhibit Enhanced Scholarly Impact
Authors: Wang Hanjay , Bajaj Simar , Williams Kiah M , Woo Y , Boyd Jack
Published: April 2022

Introduction:
National Institutes of Health (NIH) grants are an essential funding source for cardiothoracic (CT) surgeon-scientists. The association between NIH funding and an article’s research impact, however, has not been explored. We hypothesized that CT surgery research articles supported by NIH funding exhibit enhanced scholarly impact.

Methods:
Research records and NIH funding history for all CT surgery faculty (n=992) at accredited United States CT surgery training institutions in 2018 were obtained using Scopus and Grantome, respectively. Using the NIH iCite database, all articles published by these surgeons were classified as either basic science research (BSR, iCite animal or molecular/cellular score >0) or clinical research (CR, iCite animal and molecular/cellular score = 0). The relative citation ratio (RCR), an NIH-validated field-normalized metric of scholarly impact, was calculated for each article, where RCR 1.00 indicates equal impact as other NIH-funded articles in the same field, and RCR 2.00 indicates twice the impact. Data are presented as median [interquartile range] and analyzed using the Mann-Whitney test.

Results:
A total of 37,402 unique articles were identified, including 9,469 supported by NIH funding and 27,933 without NIH funding. CT surgery research articles with NIH funding exhibit a significantly greater median RCR than those without NIH funding (1.08 [0.53-2.19] vs 0.75 [0.28-1.72], p<0.0001, Figure 1A). Among BSR articles, NIH-funded papers have a significantly greater median RCR (0.93 [0.47-1.88] vs 0.62 [0.26-1.33], p<0.0001, Figure 1B). Similarly, among CR articles, NIH-funded papers also exhibit a significantly greater median RCR (1.34 [0.66-2.60] vs 0.79 [0.28-1.80], p<0.0001, Figure 1C).

Conclusions:
At single-article resolution, CT surgery research publications supported by NIH grant funding exhibit enhanced scholarly impact and compare favorably in median RCR versus other NIH-funded biomedical research.
Abstract 12297: Myocardial Bridging Increases the Risk of Preoperative Atrial Fibrillation in Adult Patients with Obstructive Hypertrophic Cardiomyopathy
Authors: Nie Changrong , Wang Changsheng , Song Yunhu , Xiao Minghu , Shuiyun WANG
Published: April 2022

Background:
Myocardial bridging (MB) was associated with various arrhythmia forms like supraventricular tachycardia, ventricular tachycardia, atrioventricular conduction block, and sudden cardiac death. However, the relationship between MB and preoperative atrial fibrillation (AF) remains unknown.

Hypothesis:
The presence of MB increases the risk of preoperation AF in adult patients with obstructive hypertrophic cardiomyopathy (OHCM).

Method:
We recruited 968 consecutive patients with OHCM who underwent surgical myectomy at Fuwai Hospital in Beijing, China, from January 2015 to December 2019. Patients were divided into two groups based on invasive coronary angiography: patients with MB group (N=144) and patients without MB group (N=824).

Result:
Patients with MB were much younger (43.6 vs. 48.8 years, p < 0.001), more likely to have palpitation (37.4% vs. 25.5%, p = 0.003), had a lower body mass index (24.8 vs. 25.7 kg/m2, p = 0.009), a lower incidence of hypertension (14.6% vs. 27.9% p = 0.001), a higher prevalence of AF (26.4% vs. 11.5%, p <0.001). After adjusting for age, sex, left atrial diameter, and LVOT gradient, multivariate logistic regression analysis revealed that the presence of MB was independently associated with AF (Odds ratio [OR] 3.73; 95% Confidential interval [CI] 2.32-5.98, p < 0.001). Furthermore, we conducted a LASSO logistic regression to select variables associated with AF from patients with MB subgroup, and five non-zero variables were included in the multivariate logistic regression model. The results indicated that compared to patients with MB on the middle left anterior descending coronary (LAD), those with MB on the proximal LAD had a higher likelihood to develop AF (OR 4.22; 95% CI 1.40-12.68, p = 0.01). Moreover, MB compression (OR 1.04; 95% CI 1.04-1.08, p = 0.013) and MB length (OR 1.06; 95% CI 1.004-1.11, p = 0.034) were independently associated with a higher prevalence of AF after adjusting for age and left atrial diameter.

Conclusion:
The presence of MB and its location, length, and compression degree were independently associated with an increased risk of preoperative AF in adult HOCM patients, which suggested that whether MB needed surgical treatment during septal myectomy should be considered.
Abstract 12299: Molecular Imaging of Active Vascular Microcalcification in the Lower Extremities of Patients With Diabetes and Peripheral Arterial Disease
Authors: Chou Ting-heng , Eisert Susan N , Ettefagh Laila , Sarac Timur P , Atway Said A , Go Michael R , Stacy Mitchel R
Published: April 2022

Introduction:
Patients with diabetes mellitus (DM) have accelerated progression of peripheral arterial disease (PAD) with higher prevalence of arterial calcification, which can limit and make options for endovascular revascularization more challenging, contribute to worse treatment outcomes, and result in higher rates of amputation. Positron emission tomography (PET) imaging with fluorine-18 (
18
F)-sodium fluoride (NaF) has shown utility for detecting active microcalcification of coronary arteries but remains relatively understudied in patients with PAD. We hypothesized that
18
F-NaF PET/CT imaging could be used to quantify DM-induced active microcalcification of lower extremity arteries.

Methods:
18
F-NaF PET/CT imaging was performed in PAD patients with type 2 DM (n=11), PAD patients without DM (n=8), and healthy controls (n=6). Regions of interest were manually drawn bilaterally on each axial slice of CT images for the femoral, popliteal, anterior tibial, tibioperoneal trunk, posterior tibial, and peroneal arteries to quantify
18
F-NaF uptake. The maximum target-to-background ratio (TBR
max
) was calculated for each artery of interest.

Results:
18
F-NaF PET/CT imaging non-invasively detected significantly higher active microcalcification of the femoral-popliteal, anterior tibial, tibioperoneal trunk, and posterior tibial arteries in patients with DM and PAD compared to healthy controls (
Fig. 1
). A noticeable trend (not significant) in increasing arterial retention of
18
F-NaF was found with increasing disease status (i.e., healthy, PAD only, PAD with DM) (
Fig. 1
).

Conclusions:
18
F-NaF PET/CT quantifies vessel-specific active calcification of above- and below-the-knee arteries in patients with DM and PAD. PET/CT may offer insight into early pathophysiology of peripheral disease in patients with DM, thereby improving personalized therapeutic approaches for a population that suffers from significant morbidity and mortality.
Abstract 12301: Anticoagulation for Left Ventricular Thrombus: An Updated Meta-Analysis of Stroke or Systemic Embolization Outcomes
Authors: Sohal Sumit , Kurpad Krishna Prasad , Nagraj Sanjana , mathai sheetal vasundara , Waxman Sergio
Published: April 2022

Introduction:
Thromboembolic events including stroke or systemic embolization (SSE) are the most dreaded complications in patients who develop left ventricular (LV) thrombus. Vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) have been used in the management of LV thrombus however the efficacy of these treatment strategies have been rarely studied in head-to-head trials. Our aim was to study the differences in embolization outcomes in patients with LV thrombus on either NOACs or VKAs.

Methods:
A comprehensive search of electronic databases was conducted for studies comparing VKAs and NOACs in patients with LV thrombus. Event level data were extracted from studies for each arm and used to calculate the risk ratio (RR) with 95% confidence intervals (CI) which were pooled for the effect of original treatment allocation on the outcome of SSE. Random effects model was used to calculate the risk ratio.

Results:
We found a total of 12 studies from which 2281 patients were identified with LV thrombus and were treated with anticoagulation. 596 (26.13%) received NOACs and 1685 (73.87%) received VKAs. Events of SSE occurred in 92 (15.44%) patients on NOACs and 307 (18.22%) patients on VKAs. Overall, patients treated with NOACs had similar rate of SSE events as compared to patients treated with VKAs using random effects model (RR: 1.02 [95% 0.64-1.65], p=0.08, I
2
=39%).

Conclusions:
This meta-analysis suggests that the use of NOACs is associated similar rate of SSE events in patients with LV thrombus as compared to the use of VKAs. Additional prospective studies are required to determine the most effective anticoagulant strategy for patients with LV thrombus.
Abstract 12306: Impact of the COVID Pandemic on Depression and Subsequent Emergency Department Visits for Anxiety and Chest Pain
Authors: May Heidi T , Bair Tami L , Le Viet T , Muhlestein Joseph B , Knight Stacey , Anderson Jeffrey L , Knowlton Kirk U , Horne Benjamin D
Published: April 2022

Background:
The COVID-19 pandemic has affected nearly every aspect of daily life. The interpersonal loss due to quarantining and social distancing, compounded with societal disruption has negatively affected mental health. Once established, mental health conditions can become chronic with having subsequent effects on additional risk factors and disease incidence, such as cardiovascular disease (CVD).

Methods:
Patients who completed a PHQ-9 in a primary care setting in the year prior to the COVID pandemic (Mar 1, 2019 to Feb 29, 2020) and during the COVID pandemic (Mar 1, 2020 to Apr 20, 2021) were studied. Patients were stratified into 2 groups: no depression/no longer depressed and remained depressed/became depressed. Patients were assessed for follow-up emergency department (ED) visits for anxiety and chest pain (CP) after PHQ-9 completion during the pandemic.

Results:
A total of 4,633 patients were studied, with 2,848 (61.5%) being never/no longer depressed and 1,785 (38.5%) remaining/became depressed. PHQ-9 scores during the pandemic were higher than prior to the pandemic among those depressed. A total of 2,171 (46.6%) received a COVID test, with more depressed patients tested compared to non-depressed (Table), but with positivity for SARS-CoV-2 (n=362 [16.7%]) being similar (p=0.18). The table shows baseline characteristics and outcomes. Depression was associated with increased ED visits for anxiety (Table). Those with depression, visited the ED at 3.5 times and 2.7 times greater rate for anxiety and anxiety with CP compared to non-depressed, respectively.

Conclusions:
Depression was highly prevalent among patients who receive routine primary care, with depressive symptoms increasing during the pandemic. Since depression and anxiety are associated with an increased risk of CVD and associated risk factors, identifying and treating patients early who exhibit such symptoms will be important in reducing the risk of future CVD and risk factor incidence.