bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10642: A Novel Way to Predict Obstructive Coronary Artery Disease Requiring Revascularization: The Use of Magnetocardiography
Authors: Coriasso Nicholas , Takla Robert B , Rodriguez David , Pearson Claire , Pena Margarita , Daher Edouard
Published: March 2022

Introduction:
Coronary artery disease (CAD) causes one-third of total deaths in people over the age of 35. The evaluation of suspected obstructive CAD includes H&P, ECG, and cardiac enzymes. These tests can often lead to diagnostic uncertainty which can then lead to unnecessary testing such as stress tests and/or coronary angiography. Magnetocardiography (MCG) has been proposed as a noninvasive, radiation free, rapid adjunctive test in predicting coronary ischemia requiring revascularization. MCG measures the magnetic fields produced by electrical currents in the heart with unique and distinct advantages over traditional electrocardiographic approaches.

Methods:
One hundred patients (62% male, 69% white, age 60.9 years), suspected of having obstructive CAD, were evaluated at a large urban community hospital. All patients underwent MCG prior to coronary angiography which was interpreted by readers blinded to clinical data. MCG was considered positive if the scan displayed findings of “RT angle”, “multipolar”, or “island”. Of the 100 patients, 72 MCG studies were interpretable.

Results:
Of the 72 MCG studies, 25 were considered positive. Of the 25, 17 revealed obstructive CAD on angiography and underwent PCI with balloon or stent. Of the 47 negative, 35 revealed no obstructive CAD on angiography. Sensitivity was 58.6% and specificity was 81.4%. Removing patients with “island” MCG features resulted in 65 studies which improved specificity to 92.1% at a slight penalty in sensitivity at 55.6%. There were 11 patients where stress testing and MCG could be compared to angiography revealing a diagnostic accuracy of 54.5% and 81.8%, respectively.

Discussion:
MCG was able to predict obstructive CAD leading to PCI with a specificity of 81.4%. Refining interpretation criteria improved specificity to 92.1% plus better diagnostic accuracy than stress testing. MCG shows promise as an adjunctive test for patients with suspected CAD who may require revascularization with PCI.
Abstract 10650: Artificial Intelligence Correlates with Expert Aortic Measurements in Presurgical CTA Evaluation for Transcatheter Aortic Valve Replacement
Authors: Lineberger John P , Mercer Megan , Aquino Gilberto , Leaphart Nathan , Dean Brian , Nance Sophia , Mulji Anand , Wortham Andrew , Chamberlin Jordan , Schoepf Joseph , Waltz Jeffrey , Burt Jeremy R
Published: March 2022

Introduction/Hypothesis:
Transcatheter aortic valve replacement (TAVR) requires pre-surgical planning via CTA. Our purpose is to compare pre-TAVR CTA expert measurements versus an AI in a pilot study.

Methods:
An AI model was created using Unett++ with a Resnet18 encoder, and was trained using transfer learning. A total of 52 randomized patients with a preTAVR CTA were identified for AI validation. The average diameter from 3 aortic segments was measured by AI: annulus, sinuses of Valsalva, and sinotubular junction. Of the original 52 subjects, 39 patients had expert measurements for comparison with AI results. Standard statistical analysis was performed.

Results:
Patients were 65% male and 88% Caucasian. The median age and BMI were 82 years and 28 kg/m2, respectively. A Sorensen-Dice coefficient of 0.93 was attained between the expert and AI measurements. Annulus (Pearson r = 0.911), sinuses of Valsalva (r = 0.919), and sinotubular junction (r = 0.874) average diameter measurements correlated with the experts’ (p<0.001 in all cases). It was shown that there was no proportional bias and that the concordance between AI and expert measurements was good to excellent (intraclass correlation coefficients = 0.909 (95% CI 0.834-0.951), 0.899 (0.766-0.952) and 0.830 (0.694-0.908) for annulus, sinuses of Valsalva and sinotubular junction). Limitations include small pilot sample with uncharacterized generalizability.

Conclusion:
In this validation study, AI measurements of the aortic annulus, sinuses of Valsalva, and sinotubular junction correlate with expert measurements. There was high inter-relater reliability for all sites. Further study will include expanded patient cohorts and accurately streamlined preoperative assessment for TAVR.

Figure.
Pre TAVR CT angiogram images in orthogonal projection for aortic annulus (A), sinuses of Valsalva (B), and sinotubular junction (C). “Ground Truth” is expert segmentation and “Threshold 0.5” is AI segmentation.
Abstract 10652: Epidemiology and Outcomes of Pulmonary Hypertension in the Cardiac Intensive Care Unit
Authors: Jentzer Jacob C , Wiley Brandon , Reddy Yogesh , Barnett Christopher F , Borlaug Barry A , Solomon Michael A
Published: March 2022

Introduction:
Pulmonary hypertension (PH), defined as an elevated mean pulmonary artery pressure, has been consistently associated with adverse outcomes in hospitalized patients. Limited epidemiologic data exist regarding PH in the cardiac intensive care unit (CICU) population. We used transthoracic echocardiography (TTE) to describe the prevalence, etiology, and outcomes of PH in the CICU.

Hypothesis:
PH will be associated with higher in-hospital mortality in CICU patients.

Methods:
CICU patients admitted from 2007 to 2018 who had right ventricular systolic pressure (RVSP) measured via TTE within 1 day of CICU admission were included. PH was defined as an estimated RVSP >35 mmHg. Predictors of in-hospital mortality were determined using multivariable logistic regression.

Results:
We included 5042 patients with a mean age of 69.4±14.8 (41% females); 81.1% had an admission diagnosis of acute coronary syndrome or heart failure. PH was present in 3085 (61%); the majority (68%) of patients with PH had left heart failure, and 29% had lung disease. In-hospital mortality occurred in 8% and was higher in patients with PH (11% vs. 4%, adjusted OR 1.40, 95% CI 1.03-1.92, p =0.03). PH was associated with higher in-hospital mortality in patients with acute coronary syndrome, heart failure or cardiac arrest (all p <0.01), but not in patients with cardiogenic shock, respiratory failure or sepsis (
Figure
). In-hospital mortality increased as a function of higher RVSP in each admission diagnosis group (adjusted 1.18 per 10 mmHg higher in the entire cohort, 95% CI 1.09-1.28, p <0.001).

Conclusions:
PH by TTE is very common in the CICU population and remains associated with a higher risk of death during hospitalization even after adjustment. TTE assessment of right heart hemodynamics can predict mortality in CICU patients, with variability across common admission diagnoses. This highlights the importance of PH determined by TTE in hospitalized patients with cardiac critical illness.
Abstract 10657: Automated Tracing of Tricuspid Regurgitation Doppler Waveforms
Authors: Pham Jonathan , Dual Seraina A , Verdonk Constance , Amsallem Myriam , Feinstein Jeffrey A , Haddad Francois , Marsden Alison L
Published: March 2022

Introduction:
The definition of pulmonary hypertension relies on the invasive measurement of increased pulmonary arterial pressures (PAPs). The systolic PAP can be non-invasively estimated from the maximal velocity (Vmax) of tricuspid regurgitation (TR) Doppler signals. However, the accuracy of this method is conditioned by the quality of the TR signal. It is also subject to high interobserver variability. To address these issues, we developed an automated, machine-learning framework to analyze TR signals. We hypothesize our method can accurately predict Vmax and velocity time integral (VTI) for any TR signal.

Methods:
We analyzed 306 TR Doppler signals consisting of high and intermediate signal qualities from 65 patients (median 50 [21, 86] years old). Our method combines a U-Net convolutional neural network with OpenCV, an image processing tool. The U-Net performs semantic image segmentation on an input TR Doppler signal. OpenCV then deduces the Vmax and VTI of the curve. We compared our predictions against expert assessments of the TR signal, Vmax, and VTI. We used 230/56 signals for training/validation to determine the optimal parameters in our U-Net and 20 signals for testing to obtain an unbiased measure of performance.

Results:
As shown in the figure, our framework accurately predicts Vmax with a bias of 0.06 m/s and 95% limits of agreement of [-0.50, 0.63] m/s, and VTI with a bias of 0.01 m and 95% limits of agreement of [-0.22, 0.23] m. Two signals proved difficult to trace due to noisy images. Our framework takes about 5 seconds to predict Vmax and VTI for each TR signal.

Conclusions:
The accuracy of the predicted Vmax and VTI is heavily influenced by the quality of the input TR signal. We can solve this issue by training our U-Net on a larger dataset and leveraging other computer-vision techniques or flagging these signals for user intervention. Automation of signal analysis opens the door for more detailed curve analysis on larger clinical cohorts.
Abstract 10659: Blood DNA Methylation at TXNIP and Glycemic Changes in Response to Weight-Loss Diet Interventions: The POUNDS Lost Trial
Authors: Li Xiang , SHAO Xiaojian , Xue Qiaochu , Grundberg Elin , Bray George , Sacks Frank , Qi Lu
Published: March 2022

Introduction:
Thioredoxin Interacting Protein (
TXNIP
) functions as a master regulator for glucose homeostasis. Hypomethylation at the 5'-cytosine-phosphate-guanine-3' (CpG) site cg19693031 of
TXNIP
has been consistently related to islet dysfunction, hyperglycemia, and type 2 diabetes. DNA methylation (DNAm) may reveal the missing mechanistic link between obesity and type 2 diabetes; however, little is known about whether the DNAm level at
TXNIP
in blood is associated with glycemic changes in response to weight-loss diet interventions.

Hypothesis:
We hypothesized that participants with varying DNAm level of
TXNIP
responded differentially to weight-loss diet interventions on glycemic changes.

Method:
We included 639 overweight and obese participants from Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, who were randomly assigned to 1 of 4 weight-loss diets varying in macronutrient contents. Blood DNAm levels were profiled by a high-resolution methylC-capture sequencing at baseline. We defined regional methylation level of
TXNIP
as average methylation level over CpGs within 500 bp of cg19693031.

Results:
Higher regional methylation level at
TXNIP
was correlated with lower fasting glucose, HbA1c, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at baseline (p<0.05 for all). Participants with distinct regional methylation level of
TXNIP
showed significantly different changes in fasting insulin (p-interaction=0.007) and HOMA-IR (p-interaction=0.009) in response to average- vs. high-protein diet intervention at 6 months, independent of weight loss. Among participants with an average-protein diet, higher regional methylation level at
TXNIP
was associated with a greater reduction of fasting insulin and HOMA-IR at 6 months, while an opposite association was found among those with a high-protein diet. Such difference was attenuated to be nonsignificant at 2 years.

Conclusions:
DNAm level at
TXNIP
in blood may modify the effects of diet interventions on changes in glycemic traits, independent of weight loss. Overweight and obese individuals with higher methylation level at
TXNIP
may benefit more in improving insulin and HOMA-IR by consuming an average-protein diet than a high-protein diet.
Abstract 10666: Epigenetic Risk Score Capturing Alcohol Consumption is Not Associated with Cardiac Structure and Function: The Framingham Heart Study
Authors: Bui Helena , Keshawarz Amena , Liu Chunyu , Ma Jiantao , Tsao Connie W , Ramachandran Vasan S , Cheng Susan , Levy Daniel
Published: March 2022

Habitual, heavy alcohol consumption increases the risk of detrimental outcomes such alcoholic dilated cardiomyopathy; however, alcohol’s complex effects on cardiac structure and function are incompletely understood. We previously identified 144 differentially methylated CpGs associated with alcohol consumption and sought to create an epigenetic risk score (ERS) derived from these CpGs to examine 1) the cross-sectional association of the ERS with cardiac structure and function, and 2) longitudinal association of the ERS with incident heart failure and atrial fibrillation in Framingham Heart Study (FHS) participants (n=1,843). We first conducted analyses examining the cross-sectional association between each of the 144 alcohol-associated CpGs and the outcomes listed above. After application of Bonferroni correction (p=3.47E-04), two CpGs (cg07504977, cg16246545) were significantly associated with left ventricular posterior wall thickness (p=2.69E-05 and p=1.75E-04, respectively) and one CpG (cg11682350) was significantly associated with left ventricular global longitudinal strain (p=2.15E-04). cg07504977 annotates to the promoter of a lcRNA LINC00623, while cg16246545 maps to the
PHGDH
, a protein-coding gene implicated in serine synthesis. cg11682350 is not annotated to a gene. Cross-sectional analyses examining the association between the ERS and left ventricular mass (BSA-indexed; p=0.15) systolic diameter (p=0.92), diastolic diameter (p=0.87), fractional shortening (p=0.95), and global longitudinal strain (p=0.28), were not statistically significant, while ERS association with LV posterior wall thickness was nominally significant (p=0.03). Longitudinal associations for HF (p=0.18) and AF (p=0.65) were not significant. Though most of our results are not statistically significant, we plan to explore other means of generating alcohol ERS including by LASSO penalty coefficient thresholds, Gene Ontology biological pathways, and weighted gene expression network analyses. In conclusion, such alcohol-related ERS may be examined in relation to other phenotypes and serve as a predictive or diagnostic tool to monitor and elucidate the epigenetic pathways connecting environmental exposures and disease.
Abstract 10669: The Association of Statin Dose and Mortality Risk Across Chronic Kidney Disease Stages in 665,858 United States Veterans
Authors: Rizk John , Hsiung Jui-Ting , Arif Yousif , Soohoo Melissa , Hashemi Leila , Marroquin Maria , Edward Jessica , Streja Elani
Published: March 2022

Rationale:
Statin therapy is associated with lower mortality risk in both general and chronic kidney disease (CKD) populations. While statin therapy is recommended for CKD patients, the intensity of statin doses remains disputed. Thus, we examined the relationship of different statin doses with all-cause and cardiovascular (CVD) mortality across CKD stages.

Methods:
The cohort consists of 665,858 US Veterans with statin prescriptions between 2004-2014 who were followed until 2014. Statin intensity was categorized into low, moderate, and high dose based on ACC/AHA guidelines. Statin dosage and all-cause/CVD mortality associations were estimated using Cox proportional hazards models adjusting for comorbidities, labs, history of percutaneous coronary intervention and coronary artery bypass grafting across CKD stages.

Results:
Cohort mean age is 62+/-12 years with 6% females and 18% Blacks. Median [IQR] of eGFR is 79[64,93] mL/min/1.73m2 with 80% non-CKD. At baseline, 38%, 59%, and 3% patients were taking a low, moderate, and high dose of statin. A lower to null risk of all-cause and CVD mortality were found in low statin dose patients (ref: moderate statin dose) for all CKD stages. Furthermore, the association of low statin dose with all-cause mortality incrementally declined as CKD stages progressed. A null association of high statin dose with mortality risk was observed for all stages, with the exception of CKD stage 5/ESRD patients, where a 30% and 39% higher all-cause and CVD mortality risk were observed. [Figure]

Conclusion:
A low statin dose was associated with lower CVD mortality risk compared to a moderate dose in non-CKD patients. Yet, a high dose was associated with higher all-cause and CVD death risk in CKD stage5/ESRD patients. Statin therapy is known to improve patient outcomes; however, different intensities of statin should be applied when dealing with patients with different CKD stages as advanced stages of CKD may require adjustment in statin dosing.
Abstract 10670: Kidney Function, Bone-Mineral Metabolism Markers, and Calcification of Coronary Arteries, Aorta, and Cardiac Valves in Older Adults
Authors: Mok Yejin , Wang Frances , Ballew Shoshana , Menez Steven , Butler Kenneth R , Wagenknecht Lynne E , Lutsey Pamela L , Coresh Josef , Blaha Michael J , Matsushita Kuni
Published: March 2022

Background:
Kidney function is a crucial determinant of bone-mineral metabolism (BMM); however, the contribution of kidney dysfunction, especially at mild to moderate stages, to vascular calcification remains controversial. Moreover, little is known about whether BMM markers are associated with coronary artery calcification (CAC) and extra-coronary calcification (ECC) beyond kidney function.

Methods:
In 1935 ARIC participants (age 73-95 years) with no coronary heart disease and data on CAC and ECC at visit 7 (2018-2019), we evaluated estimated glomerular filtration (eGFR) (based on creatinine, cystatin C, and both) and serum BMM markers (calcium, fibroblast growth factor 23, magnesium, parathyroid hormone, and phosphorus) as exposures. The exposures were modeled as weighted averages over ~15 years (visit 1 [1987-89] to visit 5 [2011-13] to allow a lag time for vascular calcification), and the outcome variables were high CAC and ECC (sex-race specific ≥75
th
vs. <75
th
percentile Agatston score) or any CAC and ECC (Agatston score >0 vs. 0) using multivariable logistic regression.

Results:
Low eGFR (overall range 30-149 mL/min/1.73m
2
), regardless of equations, was not robustly associated with high CAC and ECC. Among BMM markers, only higher phosphorus levels, even within the normal range, showed significant associations with high CAC and ECC, independent of kidney function (
Figure
). Considering presence of any calcification, results were generally consistent, although cystatin C-based eGFR <60 mL/min/1.73m
2
was associated with mitral valve calcification (present in 47%) (odds ratio 1.70 [95% CI 1.13, 2.58]).

Conclusion:
Cumulative exposure to lower eGFR showed weak associations with vascular calcification in community-dwelling older adults. Among BMM markers, phosphorus was most robustly associated with CAC and ECC beyond kidney function. Our results suggest a potential key role of phosphorus in the pathophysiology of vascular calcification.
Abstract 10671: Similar Left Ventricular Remodeling Despite Different Coupling Intervals of Frequent Premature Ventricular Contractions
Authors: Kabadi Rajiv A , James Nicholas , Torrado Juan F , Tan Alex Y , Kaszala Karoly , Ellenbogen Kenneth A , Jose Huizar
Published: March 2022

Introduction:
Left ventricular (LV) post-extrasystolic potentiation (PESP) and dyssynchrony (LVD) are proposed mechanisms that may trigger premature ventricular contraction-induced cardiomyopathy (PVC-CM). While long-coupled (LC) PVCs are characterized by higher LVD and lower PESP, short-coupled (SC) PVCs have higher PESP and lower LVD.

Methods:
Twenty-four mongrel dogs implanted with right ventricular epicardial pacemakers were randomized to short-coupled (PVC-SC; 200 to 220-ms, n = 10), long-coupled (PVC-LC; 320 to 340-ms, n = 7) bigeminal PVCs, or no PVCs (sham; n = 7). Holter monitors were obtained to confirm PVC burdens. Echocardiograms were performed at baseline and regular intervals up to 12 weeks after assignment to assess for LV remodeling by investigators blinded to group assignments. Intra- and inter-group comparisons were performed at each time point. PVC-CM was defined as LV ejection fraction < 50%.

Results:
Holter monitors confirmed similar PVC burdens in PVC-LC and PVC-SC groups. After 12 weeks (Table 1), PVC-CM developed in 9 (90%) PVC-SC and 5 (71%) PVC-LC animals (p = 0.5368) with similar LVEF reduction in both groups (PVC-SC: 44.4 ± 1.5%; PVC-LC: 44.7 ± 4.0%; p = 0.9953) compared to sham (62.6 ± 1.5%). LV end-diastolic volume was greater in the PVC-LC (67.5 ± 4.6 mL) compared to PVC-SC (57.5 ± 2.7 mL; p = 0.0171) and sham (52.1 ± 1.5 mL; p = 0.0004) groups. LV end-systolic volume and indices of LV mass were similarly elevated in PVC-SC and PVC-LC groups compared to sham.

Conclusions:
Short- and long-coupled PVCs did not differentially impact the incidence or severity of LV remodeling in this translational animal model of PVC-CM. This finding is compatible with preliminary clinical observations that PVC coupling interval does not predict the development of PVC-CM in humans. Our data suggest that PESP and LV dyssynchrony play equally important roles in the development of PVC-CM.
Abstract 10672: Long-Term Need for Heart Transplantation and Post-Transplantation Survival After Fontan Palliation
Authors: Wright Lydia K , Thomas Amanda S , Claxton J'Neka S , Suthar Divya , Shaw Fawwaz R , Mahle William T , Kochilas Lazaros , Desphande Shriprasad R
Published: March 2022

Introduction:
Fontan palliation for single ventricle frequently leads to heart failure and need for transplant; timing and factors associated with post-Fontan transplant, as well as post-transplant outcomes are not well understood.

Methods:
This is a retrospective cohort study of patients undergoing Fontan in the Pediatric Cardiac Care Consortium (PCCC), a large US-based registry of pediatric cardiac interventions. Deaths and transplants were captured in the PCCC and by linkage with the National Death Index and the Organ Procurement Transplant Network through 2019.

Results:
Between 1982 and 2003, 2,071 patients were enrolled in the PCCC and had their Fontan between 1988 and 2011. During Fontan hospitalization 151 deaths and 6 transplant listings occurred; 201 additional deaths and 148 listings occurred after discharge (Figure A). Cumulative incidence of transplant listing was 7.1% (95% CI 6.0-8.3) with the median time post Fontan being 11.1 years (IQR 5.3 - 13.8). After adjustment for risk factors, systemic right ventricle (HR 2.69; 95% CI 1.87 - 3.88) and >30-day length of stay after Fontan (HR 2.29; 95% 1.51 - 3.48) were associated with transplant listing. Among listed patients, 112 (73%) underwent isolated heart transplant, 2 (1%) underwent heart-liver transplant, 20 (13%) died on the waitlist, and 20 (13%) are alive without transplant. One-year post-transplant survival was 70% for transplants before 2010 and 95% after 2010 (Figure B). Graft failure was associated with transplant before 2010 (HR 6.34; 95% CI 2.21-18.2), diagnosis of hypoplastic left heart syndrome (HR 3.71; 95% CI 1.38 - 9.92), and bilirubin >2mg/dl at time of transplant (HR 2.79; 95% CI 1.03 - 7.58).

Conclusion:
Need for heart transplant is frequent post Fontan, but many die without listing. With significant improvements in post-transplant outcomes in recent years, timely transplant evaluation before significant end-organ dysfunction may improve survival for patients with single ventricle.
Abstract 10676: Left Atrial Strain is Associated with Supraventricular Tachycardia in Cardiac Amyloidosis Patients
Authors: Versteylen Mathijs , Brons Maaike , Arco Teske , Oerlemans Marish
Published: March 2022

Introduction:
In cardiac amyloidosis, supraventricular tachycardia is common. Probable mechanisms are left ventricular dysfunction resulting in left atrial disease, but also direct atrial amyloid infiltration. Although measurement of left ventricular global longitudinal strain is commonly used, the value of left atrial strain remains unclear.

Hypothesis:
Left atrial strain should be strongly associated with the occurrence of supraventricular tachycardia in cardiac amyloidosis patients.

Methods:
In 69 cardiac amyloidosis patients (75% male, mean age 65 years) in our Amyloidosis Expert Center, echocardiographic strain analysis was performed using EchoPAC (version 203, General Electric Healthcare) between March 2017 and May 2020.

Results:
Supraventricular tachycardia occurred in 34 (43%) cardiac amyloidosis patients, which were older (70±8 vs. 60±15 years, p=0.001) but had a similar left ventricular mass index and ejection fraction. Left atrial volume index was higher (56±21 vs. 45±18 ml/m
2
, p=0.02), left ventricular global longitudinal strain (11±4 vs. 14±4, p=0.004) and left atrial reservoir strain (12±9 vs. 23±16, p=0.001) were lower. Left atrial reservoir strain was associated with supraventricular tachycardia, independent of left ventricular global longitudinal strain or left atrial volume (B-value 0.88 (confidence interval 0.80 - 0.97), p=0.01).

Conclusion:
Low left atrial reservoir strain was associated with the occurrence of supraventricular tachycardia independent of left atrial volume and left ventricular global longitudinal strain and therefore a promising parameter in cardiac amyloidosis patients.
Abstract 10684: Aortic Dissection During Pregnancy and Puerperium: Contemporary Incidence and Outcomes in the United States
Authors: Wang Yunda , Yin Kanhua , Karlson Karl J , Edwards Niloo M , Dobrilovic Nikola
Published: March 2022

Background:
Aortic dissection (AD) during pregnancy and puerperium is a rare yet potentially fatal catastrophe for both parent and fetus, yet population-level trends in incidence and outcomes are undetermined.

Objectives:
To investigate the incidence and in-hospital outcomes of AD during pregnancy and puerperium in a US national database.

Methods:
The National Inpatient Sample, a large and publicly available all-payer inpatient care database, was queried to identify pregnancy-related AD hospitalizations using codes from the International Classification of Diseases (ICD-9 and ICD-10). Identified hospitalizations were stratified into Stanford type A AD (TAAD) and type B AD (TBAD) using the associated procedure codes. The weighted values of the hospitalizations were used to generate national estimates.

Results:
From January 2002 to December 2017, a total of 471 pregnancy-related AD hospitalizations were identified, with 106 (22.5%) being TAAD and 365 (77.5%) being TBAD. The mean age of the entire cohort was 30.9 ± 0.6 years; 52.1% were White, 20.6% were Hispanic, and 9.4% were Black. Marfan syndrome, primary hypertension, and pre-eclampsia/eclampsia were found in 21.9%, 11.3%, and 13.2%. Although trimester information was only available in hospitalizations with ICD-10 codes (18.0% of the entire cohort), we found that 58.8% of AD occurred in the third trimester. Overall, the incidences of AD, TAAD, and TBAD were 0.66, 0.15, and 0.51 per 100,000 pregnancy-related hospitalizations. We observed a trend of increasing incidence for pregnancy-related AD (Fig 1) during the 16-year study period - predominantly driven by TBAD. The in-hospital mortalities of AD, TAAD, and TBAD were 7.3%, 4.3%, and 8.1%.

Conclusions:
For the first time, we quantified the population-level incidence and in-hospital outcomes of AD during pregnancy and puerperium in the US; while its incidence is increasing, its in-hospital mortality appears better than that of the general population.
Abstract 10687: Structural Remodeling of Na
V
16 Channel Clusters Contributes to Arrhythmogenic Late Sodium Current in the Presence of D96V Mutant Calmodulin
Authors: Struckman Heather , Tarasov Mikhail , olgar yusuf , Miller Alec , Davis Jonathan P , Gyorke Sandor , Veeraraghavan Rengasayee , Radwanski Przemyslaw
Published: March 2022

Calmodulin facilitates normal sodium channel (Na
V
) inactivation, necessary to prevent proarrhythmic late sodium current (I
Na
). Previous studies have implicated Na
V
1.6 dysfunction in late I
Na
-mediated arrhythmias. Therefore we investigated Na
V
dysregulation by arrhythmogenic CaM mutant D96V.
Chinese hamster ovary
cells expressing Na
V
1.6 were transfected with either WT- or D96V-CaM. STED microscopy revealed enlarged Na
V
1.6 clusters in cells receiving D96V-CaM relative to WT. Therefore we explored Na
V
1.6 remodeling in transgenic mice with cardiac-specific expression of D96V-CaM (cD96V). Confocal microscopy confirmed expression of Na
V
1.6 and FLAG-tagged D96V-CaM in a striated pattern along with RyR2 in cD96V hearts, consistent with T-tubular localization. STORM microscopy enabled the quantitative assessment of Na
V
1.6 clustering. In both WT and cD96V hearts, ~50% of Na
V
1.6 clusters localized <100 nm from RyR2. However, Na
V
1.6 density within these regions increased 67% in cD96V relative to WT. We probed the functional impact of this surprising remodeling using SICM-guided “smart” patch clamp recording of NaV activity from T-tubule openings. The number of NaVs as well as frequency of late Na
V
1.6 burst openings were significantly increased in cD96V myocytes relative to WT (Fig 1). Previous work implicates aberrant late Na
V
1.6 activity in proarrhythmic Ca2+ mishandling. Indeed, STORM revealed significant enrichment of NCX near Na
V
1.6 in both WT and cD96V. Consistent with these data cD96V myocytes displayed larger, more frequent Ca2+ sparks relative to WT. This effect was reversed by cardiac-specific Na
V
1.6 knockout. To our knowledge, this is the first report of proarrhythmic cardiac structural remodeling secondary to a defect in calmodulin, which may shed mechanistic insight into calmodulinopathy.
Abstract 10692: Combined Methylomics and Transcriptomics Identifies a Race-Specific Signature of Ischemic Heart Failure in Atrial Natriuretic Peptide Gene Regulation
Authors: Bakshi Sayan , Pepin Mark E , Ha Chae-Myeong , Potter Luke , Wende Adam R
Published: March 2022

African Americans (AA) face a greater burden of cardiovascular diseases, including ischemic cardiomyopathy (ICM), compared to Caucasian Americans (CA). Our recent work supports that epigenetics is likely a unifying mechanism between health disparities of socioeconomic inequalities and heart failure severity; whereby environmental factors are incorporated as stable DNA modifications to confer susceptibility to heart failure.

We hypothesized that ICM possesses racially distinct methylome signatures. Cardiac biopsies from male age- and disease-matched AA (n = 14) and CA (n = 15) heart failure patients with ICM and non-ICM (NICM) were subjected to expression analysis using RNA-seq (
P
< 0.05, ±1.5-fold) and differential methylation analysis using Illumina EPIC array (
P
< 0.05, ±5%) using generalized linear models with a focus on changes corresponding to ICM and racial differences.

Comparing ICM vs NICM, both AA and CA patients showed racially distinct differentially expressed genes (594/366 within AA; 439/487 within CA; up/down respectively). Similarly, pathway analysis using the NIH’s BioPlanet database found a significant change (
Q
< 0.1) in AA for adipogenesis (25/133 overlap) and in CA for complement cascade (18/77 overlap). In contrast, racially distinct DNA methylation changes were more prominent for CA (29703/22703; up/down) compared to AA (2904/2897; up/down). Upon combining both datasets, known heart failure marker
NPPA
, which encodes Atrial Natriuretic Peptide, was found to be downregulated in ICM compared to NICM only for AA (
Q
= 0, 18.9-fold change), corresponding to hypermethylation of 6 CpG sites (
P
< 0.05, 6.4 - 11.3%).
NPPA
inhibits cardiac hypertrophy, fibrosis, and decreases inflammation. It is also used as a diagnostic biomarker in ICM. But recent trials found that AA have lower levels of
NPPA
in blood compared to CA, even in healthy condition. This patient cohort also indicated a racially diverse pattern of
NPPA
expression and methylation. Given its role in adipogenesis,
NPPA
may also explain the pathway enrichment specific to AA-ICM patients.

Our data indicate that
NPPA
may connect the socioeconomic effects through DNA methylation with clinical diversity of ICM. It also underscores the need for a better prognostic biomarker for ICM.
Abstract 10697: Both ST2 and BNP Predicts Atrial Fibrillation Independently of Heart Failure but BNP is Stronger When Used in Combination
Authors: Al-Wahaibi Kamla , Khan Iftikhar , McAdam Brendan F , Leong Tora
Published: March 2022

Background:
ST2, a novel marker of fibrosis in heart failure, may be a marker in Atrial fibrillation (AF) due to the role of fibrosis in AF. There is paucity of data suggesting the association of ST2 with AF.

Hypothesis:
To examine the association of ST2 with AF and its incremental value over traditional biomarkers.

Methods:
619 unselected patients presenting to a Cardiology service had BNP and ST2 sent. They included patients with heart failure, acute coronary syndromes, elective cardioversion for AF and cardiac catheterisation.

Results:
Their characteristics are shown in Table1. Both ST2 and BNP levels were significantly higher in patients with heart failure, chronic kidney disease (CKD) and AF. The AF group (30%) were older and had higher prevalence of heart failure and CKD. Both ST2 and BNP were associated with AF in both univariable (Table 2) and multi-variable models, and remained independent predictors when adjusted for risk factors (Table 3 Model 2). However, ST2 loses significance when BNP is added to the model (Table 2 Model 3). While ST2 levels were significantly higher in males, there was no significant interaction when stratified by sex (interaction p=0.31).

Conclusions:
Both ST2 and BNP are independent predictors of AF even after adjustment for other clinical factors. When ST2 is used in combination with BNP, raised BNP appears to be a stronger predictor of AF than ST2.
Abstract 10705: Association Between Clinical Outcomes and Bleeding Risk Factors in Very Elderly Patients with Atrial Fibrillation at High Bleeding Risk: The Fushimi Af Registry
Authors: Ide Yuya , Ogawa Hisashi , Ishigami Kenjiro , Ikeda Syuhei , DOI KOSUKE , Hamatani Yasuhiro , Yoshizawa Takashi , Fujino Akiko , ISHII MITSURU , Iguchi Moritake , Masunaga Nobutoyo , Esato Masahiro , Tsuji Hikari , Wada Hiromichi , Hasegawa Koji , Abe Mitsuru , Akao Masaharu
Published: March 2022

Background:
The ELDERCARE-AF trial demonstrated that low-dose edoxaban (15 mg once-daily) prevented stroke or systemic embolism (SE) in very elderly Japanese patients with nonvalvular atrial fibrillation (NVAF) who were inappropriate for standard oral anticoagulant therapy due to high bleeding risk. The association between clinical outcomes and bleeding risks in such patients in routine clinical practice are unclear.

Methods:
From the Fushimi AF registry, we obtained ELDERCARE-eligible patients with NVAF who aged ≥80 years, had CHADS
2
score ≥2, and had one or more bleeding risks as shown in the ELDERCARE-AF trial: low creatinine clearance (15 to 30 ml/min), a history of bleeding from a critical organ, low body weight (≤45 kg), or regular use of antiplatelet drugs. The association of the four bleeding risk factors with the outcomes was evaluated in eligible patients.

Results:
We obtained 549 ELDERCARE-eligible patients (12.8% of entire cohort, 52.8% of ≥80 years and CHADS
2
score ≥2). The median follow-up period was 1,823 (interquartile range: 809-2,900) days. The incidences (% per patient-year) of stroke/SE, major bleeding, all-cause mortality, and cardiovascular death were significantly higher in eligible patients than in non-eligible patients (stroke/SE: 4.6% vs. 2.0%, major bleeding: 3.5% vs. 1.8%, all-cause mortality: 15.5% vs. 3.9%, cardiovascular death: 2.9% vs. 0.6%, all log-rank P<0.001). Among the four bleeding risk factors, low body weight and low creatinine clearance were significantly associated with the incidence of all-cause mortality (adjusted hazard ratio [95% confidence interval], low body weight: 1.56 [1.16-2.10], P=0.003, low creatinine clearance: 1.70 [1.23-2.25], P<0.001). Low creatinine clearance was also significantly associated with the incidence of cardiovascular death (2.55 [1.35-4.81], P=0.004). However, none of the four bleeding risk factors had associations with the incidences of stroke/SE or major bleeding after multivariate adjustment.

Conclusion:
Patients with NVAF who met the inclusion criteria of the ELDERCARE-AF trial had poor clinical outcomes, and low creatinine clearance was associated with the incidences of both all-cause and cardiovascular mortality.
Abstract 10706: Alpha Aminoadipic Acid Down-Regulates Sr-bi Abca1 and Abcg1 Expression and May Regulate Plasma Lipid Profiles, Cellular Cholesterol Efflux, and Efferocytosis
Authors: Wang Chuan , Amanda C Doran , Linton Macrae F , Jane Ferguson
Published: March 2022

Introduction:
The metabolite α-aminoadipic acid (2-AAA) has been identified as a predictor of diabetes and atherosclerosis in large human prospective studies. However, the mechanisms linking this metabolite to disease pathophysiology remain unknown. Efferocytosis, a macrophage-mediated process for clearance of apoptotic cells (ACs), is critical in preventing necrosis of dead cells and triggers anti-inflammatory and pro-resolving responses in phagocytes. Cholesterol efflux from peripheral cells in atherosclerotic plaque is a critical step in Reverse Cholesterol Transport (RCT). We hypothesized that the 2-AAA pathway relates to atherosclerosis through modulation of plasma lipid profiles, cholesterol efflux, and macrophage efferocytosis.

Results:
We found a significant negative correlation between plasma 2-AAA and HDL cholesterol (r=-0.53, P<0.0001), and a significant positive correlation with triglycerides (r=0.35, P=0.006), in two separate samples of individuals with and without cardiometabolic disease (N=98), suggesting a relationship between 2-AAA and cardiovascular risk. We investigated the consequences of 2-AAA stimulation in several primary cells and cell lines. We found that 2-AAA stimulation downregulates three key genes (SR-BI (up to 86% reduction, P=0.005), ABCA1 (up to 92% reduction, P=0.007), ABCG1 (up to 94% reduction, P=0.008)) that directly relate to cholesterol efflux in THP-1 macropohages, suggesting an important role of 2-AAA in cholesterol efflux. Next, we found that treatment with 2-AAA at physiologically-relevant doses (30μM and 100μM) for times ranging from 30 minutes to 6 hours led to consistent reductions of efferocytosis of up to 60% (P<0.001) in mouse macrophages, J774 cells and Raw 264.7 cells, suggesting a pivotal role of 2-AAA in efferocytosis.

Conclusions:
Our data suggest 2-AAA is associated with plasma lipid profiles (HDL, triglycerides), cholesterol efflux, and macrophage efferocytosis. These novel data could provide a new target for the treatment of atherosclerosis.
Abstract 10710: Venous but Not Arterial Thrombus is Biologically Active: Cellular and Enzymatic Contributions
Authors: Bender Matthew T , Mix Doran S , Godwin Matthew , Aggarwal Anu , Tefera Leben , Campbell Joseph , haddadin Ihab , Tong Michael , CAMERON Scott J
Published: March 2022

Background:
Acute arterial thrombosis has devastating consequences, but urgency is rarely a factor in treating venous thrombosis, especially in the legs. Our goal was to determine the cellular content and enzymatic activity of catheter-extracted thrombus to gain insight into vascular remodeling.

Methods:
Catheter-extracted thrombosis in 27 patients with VTE (deep vein thrombosis [DVT, n=5], pulmonary embolism [PE, n=9]) and thrombotic stroke (AT, n=13) was evaluated by 2-dimensional electrophoresis, and immunoblotting (IB) for markers of platelets: (CD41), white blood cells (WBC, CD45), and red blood cells (RBC, CD235A ). Matrix metalloproteinase (MMP) isoforms were determined by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and confirmed by IB. Total MMP activity was determined by zymography, then isoform catalytic activity was validated using chromogenic substrates.

Results:
Protein concentration in 7mg thrombus was greater in VTE vs. AT (p=0,046). CD41 was similar in VTE vs. AT thrombus while CD45 (p=0.047) and CD235A (P=0.001) were greater in VTE. Only CD235A was greater in PE vs. DVT thrombus (P=0.002). Zymography identified enzymatic activity of many MMP isoforms. Of the 10 MMP isoforms assessed, only the following were identified in both VTE and AT: MMP 1,2,8,9,10,14. Protein content was greater in VTE vs. AT by IB for: MMP1 0.79±0.13 vs. 0.43±0.12, p=0.02, MMP2 (0.30±0.08 vs. 0.17±0.03, p=0.05), and MMP9 (1.3±0.38 vs. 0.26±0.06, p=0.009). MMP9 activity was far greater in thrombus from patients with VTE vs. AT (25 U±5.6 vs. 63±8.1 ng/mL.(μg protein)
-1
protein, p=0.0008).

Conclusion:
Cellular composition of thrombus in different vascular beds varies, altering susceptibility to tissue plasminogen activator and the potential for thrombus to irreversibly remodel blood vessels. Thrombus-derived biomarkers driving decisions for catheter-extraction should be prospectively evaluated in patients with VTE.
Abstract 10713: Long-Term Impact of Alcohol Septal Ablation on Left Ventricular Remodeling and Diastolic Function: Retrospective Echocardiographic Assessment
Authors: Cook Daniel , Bidwell Katrina , Blaker Noah , Taylor Eric , Tharp Peyton , Leaphart Davis , Nielsen Chris , Fernandes VALERIAN
Published: March 2022

Introduction:
Alcohol septal ablation (ASA) is a percutaneous procedure for patients with refractory hypertrophic obstructive cardiomyopathy (HOCM). Asymmetric septal hypertrophy (ASH) and systolic anterior motion of the mitral valve (SAM) results in a dynamic left ventricular outflow tract gradient (LVOTG). LVOTG leads to concentric left ventricular hypertrophy and diastolic dysfunction.

Hypothesis:
We tested the hypothesis that patients who underwent ASA for treatment of HOCM would experience left ventricular remodeling and long-term improvement in diastolic function.

Methods:
Using a patient database maintained internally we analyzed the echocardiograms of 96 patients (36:60 M:F)(Age=60.5±13.2 years) who underwent successful ASA and had a follow-up echocardiogram at least 270 days following the procedure. Parameters used to describe diastology included interventricular septal thickness (IVSd), LV mass index (LVd mass index), LV diastolic internal diameter (LVIDd), LV end diastolic volume index (LVEDVi), left atrial end systolic volume index (LAESVi), early and late velocities across the mitral valve (MV E and A, respectively), and the MV E/A ratio. A paired t-test was used to compare baseline and follow-up echocardiogram values within individual subjects.

Results:
The time between ASA and follow-up echocardiogram was 653.9±350.4 days (mean±SD). At follow-up, the resting and provoked gradients were significantly reduced. Baseline and follow-up echocardiogram values were compared, revealing a significant difference in IVSd, LVPWd, LVd mass index, LVEDVi, LAESVi, MV E velocity, MV A velocity and MV E/A ratio.
(Figure 1)

Conclusions:
Alcohol septal ablation induces significant regression of left ventricular hypertrophy and improvement in diastolic function. These changes likely contribute to long-term symptomatic improvement in patients who undergo alcohol septal ablation for treatment of hypertrophic obstructive cardiomyopathy.
Abstract 10716: Etanercept as an Adjunct Therapy for Acute Kawasaki Disease: A Long Term Follow Up
Authors: Sagiv Eyal , Buffone Ashley , Choueiter Nadine , Dahdah Nagib , Portman Michael A
Published: March 2022

Introduction:
Etanercept, a soluble TNF receptor, is beneficial when given as an adjunct to IVIg to children with acute Kawasaki disease (KD) and coronary artery (CA) involvement. A multi-center phase III trial, Etanercept as Adjunctive Treatment for Acute Kawasaki Disease (EATAK), showed that this TNF antagonist prevented progression of CA dilation over 6 weeks after acute KD.

Aims:
This study is aimed to test the long-term benefit of Etanercept in improving CA outcome.

Methods:
Patients enrolled in the placebo controlled double blind EATAK trial from 3 institutions (Seattle, Montreal, Bronx) who had CA dilation (z≥2.5) on initial presentation were included in this study (
n
=40). The percent reduction in the size of affected vessels from echocardiogram at presentation to mid-year (4-8 months), 1-year (9-23 months) and ≥2 years after diagnosis were analyzed, and two-tailed
t
test used to compare Etanercept (0.8 mg/kg x3 doses) and placebo (
n
=18) groups.

Results:
Both groups showed mean reduction (20%) in coronary artery diameter over a 2 year period (Figure). However, patients treated with Etanercept had accelerated and significantly greater improvement in diameter of affected vessels in the first 6 months after diagnosis [22% (
n
=25) vs. 6.8% (
n
=13),
p
=0.015]. The trend continued at 1-year follow up ([24.1% (
n
=35) vs. 17.5% (
n
=27),
p
=0.24], and by 2 years both groups showed similar overall change [19.6% (
n
=31) vs. 24.7% (
n
=24),
p
=0. 43].

Conclusions:
Etanercept as an adjunct treatment to IVIg in acute KD with CA involvement accelerates regression of CA dilation over at least a 6 month period after acute inflammation. Etanercept is a potent anti-inflammatory agent that has both early and long-term benefit in CA remodeling in KD. Acceleration of CA healing by Etanercept may provide long term coronary artery benefit.
Abstract 10723: Fetal Echocardiographic Assessment of Right Ventricular and Tricuspid Valve Function in Hypoplastic Left Heart Syndrome: Correlation with Postnatal Outcomes
Authors: Lowenstein Sarah , Edwards Lindsay , Caris Elizabeth , Bhat Aarti , Conwell Jeff , Lewin Mark , Arya Bhawna
Published: March 2022

Introduction:
Hypoplastic left heart syndrome (HLHS) carries significant morbidity and mortality. Transthoracic echocardiogram (echo) assessment of right ventricular (RV) function and tricuspid regurgitation (TR) correlate with HLHS outcomes. There are limited reports on RV function and TR in fetal HLHS and postnatal outcomes. We aim to correlate RV function and TR on fetal-echo (F-echo) with transplant-free survival (survival), hospital length of stay after initial surgery (LOS), and timing of Glenn (BDG) in HLHS patients.

Methods:
Imaging and clinical data of fetuses diagnosed with HLHS between February 2014 and September 2020 at our institution were retrospectively reviewed. Measurements of RV myocardial performance index (MPI) and fractional area change (FAC) were made on initial F-echo. The RV shortening fraction (SF), presence/degree of TR, and RV size by diastolic short-axis dimension were recorded. Postnatal outcomes included survival, LOS and age at BDG. Early BDG was a repair at <4 months. Mann-Whitney U test correlated F-echo measures and postnatal outcomes.

Results:
F-echo was available in 69 subjects; 22 excluded for termination/fetal demise, 9 for genetic syndromes, resulting in 38 subjects. Mean age at initial F-echo was 31.4±0.9wks, 11 referred >30 weeks from regional cardiologists (adjusted mean age 23.1±0.4wks). Subject age at time of review ranged from 7 months to 6.5 years. Eight subjects died (median age 2 months) and 3 required transplant (median age 8 months). F-echo RV MPI was significantly higher (0.372±0.09;p=0.005) and RV FAC was significantly lower (43%±6.4%;p=0.016) in HLHS non-survivors versus survivors. Fetal RV size and presence of TR were not significantly different. Subjects with initial LOS >30 days were more likely to have fetal TR (p<0.001) and RV dilation (p=0.019), but no significant RV MPI and FAC difference. No fetal measures correlated with need for an early BDG.

Conclusion:
F-echo evaluation of RV MPI and FAC in HLHS correlates with transplant-free survival. Presence of fetal TR and RV dilation correlate with a longer LOS. F-echo measures of RV function and TR function may inform prenatal counseling and postnatal outcomes for fetal HLHS.