bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17071: Cell Communication Inference in Macrophages
Authors: Taghdiri Nika , King Kevin R , Calcagno David , Fu Zhenxing , Huang Kenneth , weissleder R
Published: May 2021

Introduction:
Tissue macrophages play diverse roles in the cardiovascular system during health and disease. They have diverse functions within tissues, but our understanding of their dynamics is limited because most macrophage characterization assays are destructive and have low temporal resolution. We asked whether these cells are dynamic and interconnected.

Methods:
Here, we describe experimental and analytical methods for measuring cell dynamics and inferring communication between cells in vitro and in vivo. We created a mouse (Csf1r-Cre x GCaMP5) expressing the Cre-inducible genetically encoded calcium indicator GCaMP5 under the regulation of the innate immune promoter, Csf1r, to non-destructively quantify high-frequency cell dynamics and differentiated them in culture using m-CSF. We developed custom image analysis routines and parameterization strategies for classifying calcium responses.

Results:
Our studies revealed that calcium reporter BMDMs display minimal fluctuations at baseline but exhibit a dynamic response to immunogenic DNA sensing. DNA-induced isolated cell injury and death, which precipitated cell communication that spread with a velocity of [9μm/s], consistent with an extracellular diffusion mechanism. We developed quantitative image analysis methods that corrected for random calcium fluctuations and identified statistically significant areas of correlated calcium changes suggestive of communication. An analytical pipeline enabled quantification of calcium spike dynamics and correlations of dynamic calcium profiles of single cell sharing a local microenvironment. This resulted in an “improbable synchrony” metric that allowed localization of communication in time and space. We adapted the pipeline for in vivo studies and tested them in a dorsal window chamber model using intravital microscopy. At 2Hz sampling frequency, we identified 27 potential communication events as they responded to complex microenvironmental cues in vivo.

Conclusion:
The experimental and analytical methods for inferring cell communication provide a new quantitative toolkit for investigating known as-yet undiscovered cell communication pathways.
Abstract 17250: Quantitative T Wave Morphology Analysis in Rett Syndrome Patients
Authors: Collins Michael , Nguyen Hoang , Johnson Mark , Ryther Robin , Weisenberg Judith
Published: May 2021

Introduction:
Rett syndrome (RTT) is a genetic neurologic disorder associated with a high incidence of sudden death. Abnormal cardiac repolarization is a potential risk factor for sudden death in this population. RTT patients may have prolonged corrected QT (QTc) on electrocardiogram (ECG) that is a sensitive marker of torsades des pointes. However, other repolarization markers such as T wave morphology, the time it takes the T wave to return to baseline from peak amplitude (Tpeak - Tend), and heart rate corrected JTpeak have not been studied.

Hypothesis:
Rett syndrome patients have abnormal cardiac repolarization.

Methods:
Retrospective T wave analysis was performed using QT Guard software. T wave morphology and heterogeneity parameters of RTT patients were compared to ECGs of age and sex matched healthy controls. A composite T wave morphology score was calculated from individual feature of flatness, notching, and asymmetry; a higher score means more abnormal morphology. Heterogeneity of repolarization was represented by the principal component analysis ratio 2 (PCA-2).

Results:
57 Rett patients (260 ECG) and 121 controls (134 ECG) were studied. The RTT group had longer QTc (p = 0.001) along with more abnormal T-wave morphology scores and heterogeneity parameters when compared to controls (Tables 1, 2). RTT patients without long QTc also had more abnormal morphology scores than controls (p = 0.001).

Conclusion:
Cardiac repolarization is diffusely abnormal in RTT even in the absence of long QTc. T wave morphology analysis may be used to detect and monitor abnormal cardiac repolarization in RTT in clinical practice.
Abstract 17252: Rates and Predictors of Co-Prescribing Common Interacting Cardiovascular Medications in Atrial Fibrillation Patients on Direct Oral Anticoagulants
Authors: Shurrab Mohammed , Koh Maria , JACKEVICIUS Cynthia , Qiu Feng , Tu Karen , Conlon Michael , Caswell Joseph , Austin Peter , Ko Dennis T
Published: May 2021

Introduction:
Amiodarone and diltiazem are commonly prescribed cardiovascular medications in atrial fibrillation (AF) patients who take direct oral anticoagulants (DOACs). They are known to have drug-drug interactions (DDIs) with DOACs, increasing serum levels of DOACs by 40-60%, and potentially increasing risk of bleeding.

Objective:
To evaluate frequency of use of amiodarone or diltiazem among continuous users of DOACs in AF patients and assess factors associated with their use.

Methods:
The study population included all AF patients with continuous DOAC use in Ontario, Canada, ≥66 years, from April 1 2017 to March 31 2018. We used linked databases housed at ICES, Ontario. DOAC fill dates and days supplied per prescription were used to determine treatment durations. A maximum gap of 30 days between prescriptions was allowed. Multivariable logistic regression models were used to identify predictors of prescribing amiodarone or diltiazem among AF patients on DOACs.

Results:
In total, 5390 AF patients, ≥66 years, with continuous DOAC use were identified. Amiodarone was co-prescribed in 343 (6.4%) patients and diltiazem was co-prescribed in 604 (11.2%) patients. The presence of percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) significantly increased the odds of co-prescribing amiodarone among AF DOAC patients (OR 2.52 [95% CI 1.55, 4.10], p=0.0002 and OR 5.19 [95% CI 3.46, 7.80], p= <0.0001, respectively). The presence of chronic obstructive pulmonary disease was associated with significantly increased diltiazem co-prescription among AF DOAC patients (OR 1.55 [95% CI 1.28, 1.87], p=<0.0001) when adjusted for important patient-level factors (Tables 1&2).

Conclusions:
Among AF patients with continuous DOAC use, the presence of PCI or CABG was associated with increased amiodarone co-prescription. Future efforts should focus on examining the risk of bleeding in these vulnerable populations exposed to major DOAC DDIs.
Abstract 17255: Premature Atrial Stimulation Reveals Increased Conduction Slowing and Block in Cardiac Surgery Patients That Develop Postoperative Atrial Fibrillation
Authors: Khan Muhammad S , Sharma Vikas , Ranjan Ravi , Glotzbach Jason P , Selzman Craig , DOSDALL Derek J
Published: May 2021

Introduction:
Postoperative atrial fibrillation (POAF) is a common cardiac surgery complication that is highly associated with increased morbidity and mortality. The relation of presurgical left atrial (LA) conduction abnormalities and POAF during intraoperative premature atrial stimulation (S1S2) pacing is investigated and reported.

Hypothesis:
Intraoperative premature atrial stimulation reveals increased areas of slowed or blocked conduction in patients that develop POAF.

Methods:
High-density intraoperative epicardial mapping was conducted in 20 cardiac surgery patients with no history of preoperative atrial fibrillation (AF) both in sinus rhythm (SR) and during S1S2 pacing. A flexible array comprised of 240 electrodes was placed on the posterior LA wall in between the pulmonary veins. For each patient, the area of conduction block (CB), conduction delay (CD) and combined conduction delay and block (CDCB) for conduction velocity <0.1 m/s, 0.1 - 0.2 m/s and <0.2 m/s, respectively were quantified.

Results:
In 20 patients, 6 (30%) developed POAF. As shown in the Figure, conduction maps revealed the presence of significantly higher areas of CD (13.2±6.6% vs. 6.1±4.2%, p=0.03) and CDCB (17.5±8.7% vs. 7.4±6.4%, p=0.03), and a trend toward larger CB (4.2±3.8% vs. 1.3±2.9%, p=0.09) in patients that developed POAF for premature atrial beat S2 compared to patients that remained in SR after cardiac surgery. S1 paced beats and SR did not show significant differences in abnormal conduction percentages between patients with and without POAF.

Conclusions:
Premature atrial stimulation accentuates conduction abnormalities in cardiac surgery patients that develop POAF, revealing a pre-surgical substrate that may indicate greater risk for post-surgical atrial arrhythmias.
Abstract 17320: Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Clinical Outcomes in COVID-19
Authors: Pan Michael , Azam Tariq , Shadid Husam , Berlin Hanna , Meloche Chelsea , Feroze Rafey , Leya Jeff , O'Hayer Patrick , Anderson Elizabeth , Kaakati Rayan , bitar abbas , Padalia Kishan , Perry Daniel , Blakely Pennelope , Zhao Peiyao , Zhao Lili , Hayek Salim
Published: May 2021

Introduction:
COVID-19 is caused by infection with SARS-CoV2 which uses ACE2 as its host receptor. RAS inhibitors such as ACE-inhibitors and ARBs (ACEI/ARB) may increase ACE2 levels. ACE2 levels may also have a lung protective role in ARDS. There is concern over the safety of using these medications in patients with COVID-19.

Hypothesis:
To characterize the association of a history of ACEI/ARB use by hospitalized patients with COVID-19 and with in-hospital outcomes.

Methods:
The Michigan Medicine Covid-19 Cohort (M
2
C
2
) is an ongoing prospective observational study in which detailed clinical, laboratory and outcomes data were collected from chart review of consecutive adult patients hospitalized for COVID-19. Patients who were positive for SARS-CoV-2 infection but without symptoms of COVID-19 were not included in this cohort. We identified 490 patients admitted between March 1
st
and May 1
st
for COVID-19, of whom all 490 had data on whether they took ACEI/ARB prior to hospitalization. We examined the association between ACEI/ARB use and all-cause death, respiratory failure and acute kidney injury (AKI) during their hospitalization.

Results:
175 (35.7%) patients were taking ACEI/ARB prior to hospitalization (ACEI/ARB group; mean age 63.6 [SD 13.9]; 64% men) and 315 (64.3%) were not taking ACEI/ARB (non-ACEI/ARB group; median age 58.6 [SD 16.1]; 54.3% men). The risk of developing ARDS was not significantly different between the ACEI/ARB group and non-ACEI/ARB group (47.4% vs 43.5%, p-value 0.53) and neither was the risk death (15.4% vs 16.8%, p-value 0.97), despite a higher prevalence of comorbidities in the ACEI/ARB group including hypertension (96.6% vs 51.4%, p-value <0.001), diabetes mellitus (58.9% vs 34.6%, p-value <0.001), coronary artery disease (22.9% vs 11.4%, p-value 0.002), CHF (16.0% vs 12.1%, p-value 0.26), and CKD (32.0% vs 13.7%, p-value <0.001).

Conclusions:
Among hospitalized patients with COVID-19, prior to hospitalization use ACEI/ARB was not associated with significantly different risk of ARDS or mortality despite having higher rates of comorbidities in the ACEI/ARB group.
Abstract 17321: Guideline Recommended Statin Therapy Implementation and Cardiovascular Outcomes: Insights From a Multi-Site Healthcare Primary Prevention Cohort
Authors: Saeed Anum , Zhu Jianhui , Thoma Floyd W , MARROQUIN Oscar C , Aiyer Aryan , Gulati Martha , Virani Salim S , Reis Steven , Saba Samir , Lee Joon , Ballantyne Christie M , Mulukutla Suresh R
Published: May 2021

Background:
The 2013 and 2018 ACC/AHA cholesterol guidelines recommend using the 10-year ASCVD risk to guide statin therapy for primary prevention. Evidence of real-world consequences of non-adherence to these guidelines in primary prevention cohorts is limited. We investigated outcomes based on statin use in a large healthcare system, stratified by 10y ASCVD risk.

Methods:
Statin prescription practices in patients without CAD or ischemic stroke were evaluated
(
2013-2019). Patient categories constructed per the ASCVD risk were;
Borderline
(5%-7.4%),
Intermediate
(7.5%-19.9%) or
High
(≥20%). Guideline-directed statin intensity
(GDSI)
, at time of first event, was defined as; “none or any intensity” for
borderline
, “at least moderate” for
Intermediate
and
high
-risk groups. Mean (±SD) time to start/change to GD therapy from first interaction in healthcare, ASCVD incident rates [IR] and mortality were calculated across risk categories stratified by statin utilization.

Results:
Among 282,298 patients (mean age ~50y), 29,134 (10.3%), 63,299 (22.4%) and 26,687 (9.5%) were borderline, intermediate and high risk, respectively. Within intermediate-risk, 27,358 (43%) and 8,300 (31%) of high-risk never received any statin. Only 17,519 (65.6%) high-risk subjects who were prescribed statin, received GDSI [mean time ~1.8y]. A graded increase in ASCVD and mortality IRs was seen in all risk categories comparing statin versus no statin use
(Table).

Conclusions:
In a multi-site healthcare network, over one-third of statin-eligible patients were not prescribed statin therapy. In eligible patients, who ultimately received statins, mean time to GDSI was ~2yrs. The consequences of non-adherence to guidelines is illustrated with greater incident ASCVD events and mortality among those patients not treated with statin therapy. Further research can define identify barriers and develop healthcare system strategies to optimize preventive therapies.
Abstract 17340: Pre-LVAD QRS as an Independent Predictor of Myocardial Recovery in Chronic Heart Failure Patients Supported With Left Ventricular Assist Device
Authors: Khan Muhammad S , Taleb Iosif , Dranow Elizabeth , Kyriakopoulos Christos , Pinzon Omar W , Ranjan Ravi , MCKELLAR Stephen H , Selzman Craig , Kfoury Abdallah G , Caine William , Drakos Stavros G , DOSDALL Derek J
Published: May 2021

Introduction:
Left ventricular assist device (LVAD) therapy aims to improve LV reverse remodeling, but still >50% of chronic heart failure (CHF) patients show ‘no’ recovery. The current clinical paradigm to assess post-LVAD myocardial recovery relies on ventricular rotational and deformational mechanics. Investigating the role of a pre-LVAD QRS as a potential indicator for post-LVAD LV recovery in CHF patients may help clinicians develop optimal care plans for LVAD patients.

Hypothesis:
Pre-LVAD short QRS has potential value to be useful as an independent predictor for early myocardial recovery following LVAD implantation.

Methods:
Chronic and dilated cardiomyopathy patients (n=315) undergoing LVAD implantation were retrospectively studied. Acute HF etiology and post-LVAD follow up (<3 months) were exclusion criteria. Post-LVAD myocardial recovery criteria for responders (R) is defined as post-LVAD implant follow-up LVEF ≥40% and LVIDd ≤6 cm. Non-recovery (NR) criteria is defined as follow-up LVEF <40% and LVIDd < or >6 cm. From 315 LVAD patients, 39 fulfilled the criteria of myocardial recovery as ‘R’.

Results:
Based on univariate logistic regression, pre-LVAD QRS duration is found to be a predictor of myocardial recovery following LVAD implantation (OR:0.986, 95% CI:0.976-0.996, p=0.005) in LVAD patients. QRS duration is 14.5% longer in the ‘NR’ group as compared with the ‘R’ group (145±36 ms vs 124±37 ms). In multivariate logistic regression, after adjusting for previous thoracotomy, beta-blockers, and a previously evaluated composite score (UCARS) including age, HF duration, and LVEDD, pre-LVAD QRS remains a significant predictor of ‘R’ status (OR:0.983, 95% CL:0.973-0.994, p=0.003). The model shows an accuracy of 0.74 with a p-value of <0.001.

Conclusions:
Pre-LVAD short QRS interval is associated with post-LVAD LV reverse remodeling in the ‘R’ group, and thus could be of use in a clinical setting for predicting post-LVAD early myocardial recovery.
Abstract 17341: Obesity is Associated With Progressive Heart Failure in Hypertrophic Cardiomyopathy
Authors: Sridharan Aadhavi , Maron Martin S , Huang Dou , Cooper Craig , Drummond Jennifer , Maron Barry J , Rowin Ethan J
Published: May 2021

Background:
The impact of comorbid disease states and lifestyle on the natural history of patients with hypertrophic cardiomyopathy (HCM) remains unknown.

Objective:
Evaluate the association of non-HCM comorbidities including obesity, hypertension, diabetes, obstructive sleep apnea, kidney disease, tobacco use, alcohol use, and lung disease with disease progression in a large cohort of HCM patients.

Methods:
2269 patients evaluated at the Tufts HCM Institute between 2004 to 2019, ≥ 18 years of age (54 ± 15 years; 1392 male), and followed for an average of 4 ± 3.4 years for disease progression including progressive heart failure (HF) symptoms (from NYHA class I/II to NYHA class III/IV), new-onset atrial fibrillation (AF), or sudden death (SD) event (including appropriate defibrillation for ventricular arrhythmias, resuscitated cardiac arrest, or SD).

Results:
Of 1376 patients with NYHA class I/II symptoms at initial clinical evaluation, 252 (18%) developed progressive HF symptoms to NYHA class III/IV over follow-up (5%/year). Obesity (BMI ≥ 30) was significantly more prevalent in patients who had progressive HF during follow-up (43%) compared to those who remained without HF (34%, p = 0.014). In contrast, other comorbidities were not significantly associated with progressive HF symptoms (p > 0.10 for all other comorbidities). Of the 1823 patients without AF history at initial clinical visit, 198 (11%) developed new-onset AF over follow-up (3%/year). No comorbidities were significantly associated with new-onset AF in HCM (p > 0.10), although obesity was more common in patients who developed new-onset AF (48%) compared to those who had no AF (41%, p = 0.08). Notably, SD events were not associated with non-HCM comorbidities (p > 0.10 for all comorbidities), and patients with SD events were less likely to have comorbidities than patients without SD events.

Conclusions:
In adult HCM patients, obesity is associated with progressive symptoms and outcomes supporting weight loss as an important modifier in obese HCM patients to potentially help prevent HCM complications. In contrast, other non-HCM comorbidities do not appear to impact disease course, and SD events are not associated with comorbidities in HCM.
Abstract 17355: Rural-Urban Differences in the Association of Change in County-Level Physician Density With Cardiovascular Disease Mortality
Authors: Pierce Jacob B , Petito Lucia , Khan Sadiya
Published: May 2021

Introduction:
Rural areas face greater challenges in access to cardiovascular care related to lower physician density compared with urban areas. However, whether the association between recent changes in primary care physicians (PCP) and cardiologist density and contemporary CVD mortality differs by county-level urbanization is unknown.

Hypothesis:
Decreases in county-level physician density per capita between 2011-2017 will be associated with higher CVD mortality in rural compared with urban counties in 2017-18 in the US.

Methods:
Death certificates from CDC WONDER with CVD (ICD-10 codes I00-09, I11, I13, I20-51) listed as the underlying cause of death between 2017-2018 were queried to calculate age-adjusted mortality rate (AAMR) at the county-level. Changes in county-level PCPs (2011-2017) and cardiologists (2011-2017) per 100,000 population were derived from the Area Health Resources Files. We performed univariable and multivariable linear regression to determine the association between change in physician density and county-level CVD AAMR adjusted for county-level demographic and socioeconomic characteristics and baseline physician density.

Results:
PCP and cardiologist density was lower in rural counties compared with urban counties (Table). Between 2011 and 2017, PCP density decreased in rural (-2.2 [SD 15.8]) and increased in urban counties (0.8 [9.1]). Conversely, cardiologist density increased in rural (0.1 [1.8]) and decreased in urban counties (-0.1 [2.1]). Increases in PCP density were associated with lower CVD AAMR in both rural and urban counties (p<0.01). However, changes cardiologist density were not associated with lower CVD AAMR in multivariable analyses.

Conclusion:
Cardiologist density in rural counties was less than one-third that of urban counties and was not associated with CVD mortality. Increases in PCP density between 2011-17 was significantly associated with lower CVD AAMR in 2017-18 in both rural and urban counties.
Abstract 17363: Cardiac Output and Valve Orientation Affect Blood Flow Patterns Local to Bioprosthetic Pulmonary Valves in Tetralogy of Fallot
Authors: Schiavone Nicole , Elkins Christopher , McElhinney Doff B , Eaton John K , Marsden Alison L
Published: May 2021

Introduction:
Tetralogy of Fallot (ToF) typically requires surgical repair of the right ventricular outflow tract (RVOT) and subsequent placement of an artificial pulmonary valve. Bioprosthetic valve longevity is highly variable and there is currently little understanding of what hemodynamic factors may lead to early valve dysfunction.

Hypothesis:
We hypothesize that cardiac output and valve orientation impact the performance of bioprosthetic valves by affecting blood flow patterns in the RVOT.

Methods:
We analyzed hemodynamics in a 3D printed ToF anatomy model in a physiological flow loop. A 25mm surgical valve was implanted in the model at two orientations: native and rotated 180 degrees. Full 3D, three-component, phase-averaged velocity fields were obtained over the cardiac cycle using 4D flow MRI at cardiac outputs of 2, 3.5, and 5 L/min. We acquired images of valve leaflet motion at 1500Hz. The 4D flow MRI and high-speed camera experiments were run identically, allowing us to examine the relationship between flow fields and leaflet motion.

Results:
The full velocity fields from the MRI scans revealed key differences among cases in flow features including location of reverse flow regions, systolic jet shape, and asymmetry local to the valve. At 2 L/min, the forward flow through the jet was more asymmetric compared to the other cases and a strong vortex formed, indicating a region of recirculation. With the rotated valve orientation, the 2 L/min case also produced a unique pattern as flow was washed from the RVOT inner curve back toward the center of the valve (Fig 1). Leaflet behavior during systole varied with cardiac output as well, as higher frequency flutter was observed at 5 L/min and the effective valve orifice area was decreased by 8.5% at 2 L/min compared to 5 L/min.

Conclusions:
We observed key differences in flow patterns and leaflet motion due to cardiac output and valve orientation that could impact leaflet loading and fatigue and long-term valve function.
Abstract 17364: G-protein Signaling Regulation of the Hippo Pathway in Neonatal Heart Regeneration
Authors: Sakabe Masahide , Hassan Aishlin , Xin Mei
Published: May 2021

Introduction:
The regeneration potential in the adult mammalian heart is very limited due to the cessation of cardiomyocyte proliferation shortly after birth. Recent studies have revealed that changes after birth such as metabolic state, oxygen level, cardiomyocyte structure and maturity, immune system and polyploidy are among the factors contributing to the loss of the regenerative potential in the heart. The mechanisms that regulate the cardiac regenerative window are not well understood. Here we report that G-protein mediated signaling regulates Hippo-YAP in neonatal cardiomyocyte proliferation and heart regeneration through Rho activity.

Hypothesis:
Gas encoded by the
Gnas
gene, a downstream effector of beta-adrenergic receptor (βAR) inhibits cardiomyocyte proliferation via regulation of YAP activity.

Methods:
We pharmacologically inhibited the G protein coupled receptor mediated β adrenergic signaling with a β-blocker (metoprolol) at early postnatal stages, and genetically by deleting
Gnas
in the heart with αMHC-Cre. We accessed the cardiomyocyte proliferation, heart regeneration in these mice and elucidated molecular mechanisms.

Results:
We found that β-blocker enhanced cardiomyocyte proliferation and promoted cardiac regeneration post cardiac injury with improved cardiac function. Consistent with β-blocker treated mice, mice lacking Gnas in cardiomyocytes exhibited enlarged hearts with an increase in cardiomyocyte proliferation. RNA-seq analysis revealed that these cardiomyocytes maintained an immature status even at young-adult age. The genes associated with mitochondrial oxidative metabolism, the major energy source for mature cardiomyocytes, were downregulated. Moreover, YAP activity was upregulated in both cases. We also found that loss of Gαs function caused upregulation of RhoA activity, and inhibitor of Rho signaling pathway suppressed the YAP activity in cardiomyocytes.

Conclusions:
Our study reveals that Gαs negatively regulate cardiomyocyte proliferation and provides mechanistic insight for β-blocker treatment as a strategy for inducing cardiac dedifferentiation and proliferation in injured heart.
Abstract 17376: Atrial Arrhythmias in SCAD Patients
Authors: Tarabochia Alex D , Tan Nicholas Y , Hayes Sharonne N , Best Patricia J , Gulati Rajiv , Deshmukh Abhishek , Tweet Marysia
Published: May 2021

Introduction:
Spontaneous coronary artery dissection (SCAD) is an uncommon but increasingly recognized cause of acute coronary syndrome and sudden cardiac death. We aim to review the occurrence of atrial fibrillation and atrial flutter in the Mayo Clinic SCAD Registry (MCSR) to gain insight into the association of SCAD and atrial arrhythmias.

Methods:
Atrial arrhythmias were queried amongst patients in the MCSR using diagnostic codes and text contained in both a large data repository known as the Advanced Cohort Explorer as well as a clinical database maintained by nurse abstractors for patients in the MCSR. All positive were manually verified using available medical records. Univariable logistic regression analysis was performed using JMP to investigate associations with classic cardiovascular risk factors.

Results:
A total of 1,215 patients from the Mayo SCAD registry were included. Six patients had a pre SCAD atrial arrhythmia, 19 had an atrial arrhythmia during a SCAD event, and 11 had a post SCAD atrial arrhythmia. Univariable analysis did not reveal significant associations with diabetes, hypertension, hyperlipidemia, or smoking.

Conclusion:
Atrial arrhythmias were not uncommonly seen in patients at the time of or after SCAD, especially after cardiac arrest or coronary artery bypass grafting. No significant associations with traditional cardiovascular risk factors were observed. Further investigation into the mechanism of atrial arrhythmia development as well as its management in the setting of SCAD is warranted.
Abstract 17388: Loss of Bone Morphogenetic Protein 9 (BMP9) Limits Survival and Paradoxically Increases Collagen Abundance, but Limits Collagen Cross-Linking in a Murine Model of Acute Myocardial Infarction
Authors: Bhave Shreyas , Esposito Michele , Swain Lija , QIAO Xiaoying , Martin Gregory , Dasgupta Queeny , Black Lauren D , Zhang Yang , Georgakoudi Irene , Kapur Navin K
Published: May 2021

Myocardial infarction (MI) is a major cause of heart failure (HF). HF is associated with adverse cardiac remodeling that is primarily driven by Transforming growth factor beta (TGFb1) mediated fibrosis and myocyte hypertrophy. We previously reported that loss of bone morphogenetic protein 9 (BMP9) promotes cardiac fibrosis in pressure-overload induced HF. No studies have explored a role for BMP9 in post MI cardiac remodeling. We hypothesize that loss of BMP9 may promote cardiac healing by stabilizing LV scar formation. To test this hypothesis, we subjected whole body BMP9 knockout (-/-) mice to left coronary artery ligation for two weeks followed by PV loop analysis and studied indices of cardiac remodeling. Compared to wild type (WT) controls BMP9-/- mice had significantly lower survival (83% vs 61%, p<0.001, respectively) with a higher rate of cardiac rupture(15% vs 90%). Compared to WT controls, surviving BMP9-/- mice had higher LVEDP, reduced LV dP/dt, and higher lung weight. Compared to WT mice, BMP9-/- mice had significantly higher levels of Type I collagen (2 fold p<0.05). Compared to WT mice, BMP9-/- mice had increased matrix metalloproteinases (MMP)-2 and MMP-9 (2.5 fold p<0.05) activity levels in the LV. Treatment of cultured primary human cardiac fibroblasts with recombinant BMP9 attenuated TGFb1-mediated Type I collagen and MMP-9 protein expression. To assess collagen content and cross-linking, two-photon excitation fluorescence imaging was performed and identified an increase in collagen abundance, but a trend towards lower collagen cross-linking in the LV of BMP9-/- mice compared to WT mice 2 weeks after MI. Our central finding is that loss of BMP9 is associated with reduced survival, increased propensity towards cardiac rupture, and increased LV collagen abundance, but reduced collagen integrity in a murine model of acute MI. These identify a potentially important functional role for BMP9 in post-infarct cardiac remodeling.
Abstract 17389: Antiplatelets Agents Decreases 30-days Mortality in Myocardial Injury After Noncardiac Surgery
Authors: Jogu Hanumantha R , Chevli Parag A , Nadella Geeth Sandeep , Islam Tareq S , Dutta Abhishek , Sunkara Padageshwar , Barot Harsh , Thazhatuveetil-Kunhahamed Luqman-Arafath , Huang Chi-Cheng , Beekman Daniel
Published: May 2021

Introduction:
Despite being frequent and associated with poor outcomes, no guidelines exist addressing the management of myocardial injury after noncardiac surgery (MINS). We hypothesized that Antiplatelets (ATP) agents reduce 30-days mortality in MINS patients.

Methods:
We used data from the Wake-Up T2MI registry, which is a single-center, retrospective cohort of hospitalized adults with elevated troponin (cTn) I (> 99
th
percentile reference upper limit is >0.04 ng/dL) without acute myocardial infarction in a 2-year period. Patients with the cardiac procedures were excluded and cTn obtained during hospitalization. MINS is defined as abnormally elevated cTn levels during or within 30 days after surgery. Kaplan-Meier curve and multivariate-adjusted Cox-proportional hazard models were performed to assess all-cause mortality at 30-days, 90-days, and 1-year among patients with and without ATPs upon discharge.

Results:
A total of 457 patients were included in the final analysis. There was no difference in sex, race, BMI, and peak cTn, except age among patients stratified by ATP on discharge. Prevalence of mortality was significantly lower at 30-days (2.6% vs 7%, p = 0.028), it was not significant at 90-days (9.6% vs. 11.8%, p = 0.440) and at 1-year (21.4% vs. 24.6%, p=0.421) in patients who were discharged on ATPs compared to non-ATPs. Survival benefit was significant at 30-days (log-rank p = 0.022), non-significant at 90-days (log-rank p = 0.292) and at 1-year (log-rank p = 180) in ATPs group compared to non-ATPs. In a multivariate-adjusted (adjusted for age, sex, race, and peak cTn) model, patients who were discharged on ATPs had a HR of 0.31 (0.120 - 0.799; p = 0.015) at 30 days, HR of 0.64 (0.363 - 1.136; p = 0.128) at 90 days (Figure 1), and HR of 0.69 (0.472 - 1.025; p = 0.066) at 1 year.

Conclusions:
In conclusion, antiplatelet agents on discharge were associated with decreased 30-days mortality in MINS patients. Further studies are needed to validate our results.
Abstract 17390: Maternal and Fetal Cardiovascular Adaptations to Pregnancy and Outcomes in Mothers With Cardiac Disease - A Magnetic Resonance Imaging Study
Authors: Saini Brahmdeep S , Ducas Robin , Kenichiro Yamamura , Seed Mike , Wald Rachel M
Published: May 2021

Introduction:
Insufficient maternal cardiac output (CO) has been implicated in poor pregnancy outcomes in mothers with heart disease (HD). Simultaneous delineation of vascular flows in the mother and her fetus have not been reported but could contribute to our understanding of the mechanisms of adverse events in this susceptible population.

Methods:
Pregnant women with moderate or severe HD (n=22; age 32±5 years) were studied using magnetic resonance imaging (MRI) and were compared with healthy controls (n=21; 34±3 years). Each MRI study included maternal and fetal components during the third trimester of pregnancy (corresponding to peak CO) and six months postpartum (surrogate for baseline hemodynamics). Phase contrast (PC) imaging was used to quantify maternal and fetal vascular flows. Fetal vessel T1 and T2 oximetry was used for derivation of fetal oxygen delivery and consumption. Maternal cardiac index (CI) was calculated using CO and pre-pregnancy body surface area. In the HD group, an “adapter” to pregnancy was defined as a woman with peak pregnancy CI measurement which met or exceeded the mean CI in the control population. Maternal and fetal outcomes were recorded.

Results:
There was no antepartum differences in absolute CO or CI in HD versus controls (CO 7.2±1.5 versus 7.3±1.6 L/min, p=0.79; CI 4.0±0.7 versus 4.3±0.7 L/min/m
2
, p=0.28). The percent increase in CO and CI (antepartum minus postpartum) was greater in women with HD versus controls (CO 46±24% versus 27±16%, p=0.02; CI 51±28% versus 28±17%, p<0.01). Fetal growth and oxygen delivery/consumption were similar between groups. Six adverse maternal cardiovascular events occurred in the HD group (heart failure n=2 and arrhythmia n=4) and there were none in the control group. There were no adverse fetal events in either group. There were 6 HD adapters (30%) and the adverse event rate was lower as compared with non-adapters (0% versus 38%, p=0.03).

Conclusions:
Maternal and fetal vascular flows can be characterized in pregnancy using MRI. Impaired adaptation to pregnancy in women with HD, as determined by magnitude of change in CO/CI, appears to be associated with adverse outcomes of pregnancy in the mother.
Abstract 17400: Using Electronic Health Records for Predicting Hospitalization of COVID-19 Patients in Massachusetts
Authors: Dashti Hesam , Roche Elise C. , Bates David W. , Cook Nancy R , Mora Samia , Demler Olga
Published: May 2021

Introduction:
The electronic health record (EHR) provides a platform to design models for predicting the severity of illness in COVID-19 patients. We used the Mass General Brigham (MGB) EHR that contains records mostly from greater Boston, Massachusetts. The objective of this research is to predict risk of hospitalization in patients who tested positive for COVID-19.

Methods:
Between 01/01/2020 to 05/11/2020 the MGB EHR contained 8,213 laboratory- confirmed COVID-19 patients. We queried the EHR for medical records of these patients from 12/31/2015 to 05/11/2020. To examine pre-COVID-19 medical history, we considered latest records prior to 21 days before the first COVID-19 positive test. To consider patients who were hospitalized before their test results become available, we analyzed admission records from 7 days before the first positive test. We used patients with no missing medical records to construct our dataset (N=2,783) and conducted a forward feature selection on 51 variables to identify markers that minimized the Akaike information criterion for predicting hospitalization. These markers then were used to train a generalized linear model on a subset of the dataset of MGB non-employees (N=2,367; 56% hospitalized). The trained predictive model was then tested on the remaining subset of the dataset that contains MGB employees (N=416; 17% hospitalized).

Results:
The model based on EHR data predicted risk of hospitalization well, with area under the curve (AUC, DeLong method) of 0.76 [95% CI: 0.7002-0.8206], Figure. Significant determinants of hospitalization risk included demographic variables (age, sex, race), prior medication use (heparin, erythropoietin, and beta blockers), and lab tests (albumin and white blood cell counts).

Conclusions:
EHR data of COVID-19 patients can be leveraged to predict risk of hospitalization among COVID-19 patients. Further validation of the predictive model on other cohorts is needed.
Abstract 17409: Improved Diagnosis of Coronary Artery Disease Using Cardiac CT Compared With Exercise Stress Testing in an Urban Public Hospital Patient Population
Authors: Wu Johnny , Rudenko Ivan , Shekar Chandana , Dahal Suraj , Kinninger April , Budoff Matthew J , Roy Sion
Published: May 2021

Introduction:
Heart disease remains the leading cause of death in the United States, with the disease burden particularly high in various racial and ethnic groups. In serving an underserved population comprised largely of Hispanic and African American individuals, it is crucial for an urban public hospital to diagnose heart disease in a resource-efficient and cost-effective manner. The greater positive predictive value of cardiac CT relative to exercise stress testing presents the opportunity for such hospitals to optimize resource utilization in identifying patients with coronary artery disease (CAD).

Hypothesis:
The positive predictive value of cardiac CT in diagnosing CAD is greater than that of exercise stress testing in the patient population served by an urban public hospital.

Methods:
Patients at Harbor-UCLA Medical Center (Torrance, California) were identified for inclusion in this observational study on the basis of a positive (i.e., abnormal) exercise stress test result or a positive cardiac CT result, during the period between January 2015 and September 2019. These patients were subsequently referred for invasive coronary artery angiography, with the diagnosis of obstructive CAD established by an indication for revascularization via percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Data were analyzed using a two-tailed Z-test for two proportions.

Results:
Seventy-six catheterization laboratory results were analyzed. Fifteen subjects with an abnormal exercise stress test result, out of a total of 41 (36.6%), had an indication for PCI or CABG. Twenty-five cardiac CT imaging subjects, out of a total of 35 (71.4%), had an indication for PCI or CABG. The proportion of positive cardiac CT results with an indication for PCI or CABG was significantly higher than the abnormal exercise stress test proportion (p=0.0024).

Conclusions:
Among urban public hospital patients who were referred for invasive coronary artery angiography, it was determined that cardiac CT provides a greater positive predictive value in the diagnosis of obstructive CAD than exercise stress testing. This result may help guide the optimal allocation of diagnostic resources in an urban public hospital.
Abstract 17410: Geographic and Racial/ Ethnic Disparities in Heart Transplant Listing by County and Associated Risk Factors
Authors: Parizo Justin T , Rodriguez Fatima , Sandhu Alexander T , Desai Manisha , Khush Kiran K
Published: May 2021

Introduction:
It is unknown if there are disparities in the transition from heart failure (HF) to listing for heart transplant (HT), although there are clear disparities in this transition in the transplant of other organs.

Methods:
We used CDC WONDER data and SRTR transplant data to identify county-level age-adjusted HF mortality and number of candidates listed for HT from 2006 to 2018 among racial/ ethnic subgroups. We determined rates of candidate listing and age-adjusted HF deaths (AAHFD) per 100,000 persons on aggregate and by racial/ ethnic subgroups. County-level demographic, socioeconomic, cardiovascular disease risk, and healthcare factors from public databases were used in multivariate models to determine factor groups explaining variation in candidates listed per AAHFD.

Results:
The median (IQR) candidates per AAHFD for the aggregated county cohort was 1.3 (0.75-2.0; 2558 counties reported data), the non-Hispanic white (NHW) county cohort was 1.5 (0.88-2.2; 2426 counties), the non-Hispanic black (NHB) county cohort was 1.1 (0.64-1.6; 860 counties), and the Hispanic county cohort was 1.1 (0.67-1.8; 254 counties) (p-value <0.001). The lowest candidates per AAHFD were in the South for NHW (median 1.3) and NHB (0.97), but in the West for Hispanic (0.84). Multivariate models with all county-level variables, explained (R
2
) 28.7%, 38.7%, and 57.3% of variation in candidates listed per AAHFD for NHW, NHB, and Hispanic cohorts, respectively. Socioeconomic factors (R
2
0.14), healthcare factors (R
2
0.21), and cardiovascular disease risk factors (R
2
0.18), respectively, explained the greatest variation in models using variable subgroups.

Conclusions:
When age-adjusted rates of HF mortality by race/ ethnicity group is considered, HT candidate listing for NHB and Hispanic candidates is 27% lower than for NHW. County-level factors that explain variation in HT listing vary by racial/ ethnicity group, and explain more variation in NHB and Hispanic cohorts.
Abstract 17421: Use of a Novel Septal Occluder Device for Left Atrial Appendage Closure in Patients With Post-Surgical and Post-Lariat Leaks or Anatomies Unsuitable for Conventional Percutaneous Occlusion
Authors: Della Rocca Domenico G , Horton Rodney , Tarantino Nicola , Di Biase Luigi , Gianni Carola , TRIVEDI CHINTAN G , Bassiouny Mohamed , Gallinghouse G Joseph , Al-Ahmad Amin , Sanchez Javier , Mohanty Sanghamitra , Natale Andrea
Published: May 2021

Introduction:
Interventional therapies aiming at excluding the left atrial appendage (LAA) from systemic circulation have been established as a valid alternative to oral anticoagulation (OAC) in patients at high thromboembolic (TE) risk. However, their efficacy on stroke prophylaxis may be compromised owing to incomplete LAA closure. Additionally, the need for an alternative TE prevention may remain unmet in patients with contraindications to OAC whose appendage anatomy is unsuitable for some conventional devices commercially available.

Hypothesis:
We aimed at evaluating the feasibility of LAA closure with the novel Gore® Cardioform Septal Occluder (CSO) in patients with incomplete appendage ligation or anatomical features which do not meet the manufacturer’s requirements for Watchman deployment.

Methods:
Twenty-one consecutive patients (mean age: 72±6 years; 85.7% males; CHA
2
DS
2
-VASc: 4.5±1.4; HAS-BLED: 3.6±1.0) were included. Trans-esophageal echocardiography (TEE) was performed within 2 months to assess for residual LAA patency.

Results:
Fourteen patients had incomplete LAA closure following surgical (n=6) or Lariat ligation (n=8). In 7 patients with an appendage anatomy unsuitable for Watchman deployment, the mean maximal landing zone size and LAA depth were 14.4±1.3mm and 18.6±2.8mm. Successful CSO deployment was achieved in all patients. No peri-procedural complications were documented.Procedure and fluoroscopy times were 46±13min and 14±5min. Follow-up TEE after 58±9 days revealed complete LAA closure in all patients.

Conclusions:
Transcatheter LAA closure via a CSO device might be a valid alternative in patients with residual leaks following failed appendage ligation or whose LAA anatomy does not meet the minimal anatomical criteria to accommodate a Watchman device.
Abstract 17426: Acute Myocardial Infarction Due to Right Coronary Artery Occlusion Following Blunt Thoracic Trauma
Authors: O'Dell Kimberly , Mok Jacob , Sikanderkhel Saad
Published: May 2021

Blunt thoracic wall trauma can rarely lead to acute coronary artery injury and occlusion , and mostly involves the left anterior descending artery due to its vulnerable anterior anatomic positioning. Herein, we present a case of a young man who presented as a ST segment elevation MI (STEMI) with right coronary artery (RCA) occlusion after a blunt thoracic wall trauma. Clinical Vignette: A 37-year-old man with no previous medical history was brought to our ER with blunt chest wall trauma following a motor vehicle collision. Initial workup showed multiple fractures, a right pneumothorax and a pelvic hematoma. EKG performed for chest pain showed STEMI in the inferior and lateral leads. A 2D echocardiogram then showed inferolateral wall hypokinesis. Serial troponin I levels trended up sharply from 0.4 initially. After initiating intravenous heparin and cangrelor, the patient underwent emergent coronary angiography which revealed a rare, RCA occlusion with a thrombus. The patient then successfully underwent aspiration thrombectomy with restoration of TIMI grade III blood flow.

Discussion:
Hence, we presented a rare case of RCA occlusion resulting from blunt thoracic wall trauma. While musculoskeletal pain may mask the symptoms of myocardial hypoperfusion, a high index of suspicion for coronary artery thrombosis can lead to desirable outcomes in such patients.
Abstract 17427: Electrophysiological Characteristics and Results of Catheter Ablation for Septal Flutter After Pulmonary Vein Isolation
Authors: Badhwar Nitish , Kapoor Ridhima , Johnson Colleen , Deckert Emily , Viswanathan Mohan N , Oommen Santosh , Brodt Chad , SCHEINMAN Melvin M
Published: May 2021

Background:
Septal left atrial flutter has been described de novo and has been associated with lower catheter ablation success rate.

Objective:
To describe the electrophysiological characteristics and results of catheter ablation in patients with septal atrial flutter presenting after atrial fibrillation (AF) ablation.

Methods:
We retrospectively reviewed patients who presented with atrial flutter after PVI at 3 different centers. These included patients who had undergone surgical ablation and extensive catheter ablation for AF.

Results:
The study included 13 patients with septal atrial flutter. 6 patients presented after surgical ablation (including LAA clipping). All patients had undergone PVI and posterior wall isolation. Figure shows the 12 lead ECG and 3D electroanatomic map in one patient after surgical ablation of AF. The 12 lead ECG shows positive P waves in inferior leads, flat in I and avL with early precordial transition. The 3D map shows early activation on both sides of the septum with early meets late on septal side of the mitral annulus. The voltage map showed lack of voltage in posterior wall. Entrainment mapping was helpful in identifying both sides of the septum including septal mitral annulus, anterior roof and coronary sinus as part of the circuit. Catheter ablation was acutely successful in terminating flutter in 70% of the patients. The cycle length prolonged in the remaining patients. There was early recurrence leading to success rate of 50% after single ablation.

Conclusion:
Septal flutter after extensive catheter ablation and surgical ablation for AF is associated with low voltage in posterior wall. It involves a large circuit including both sides of the septum, anterior roof and CS.
Abstract 17448: Comprehensive Characterization of Alternative Polyadenylation in Human Right Ventricle Failure
Authors: Amirthalingam Thandavarayan Rajarajan , Collum Scott D , Youker Keith , Mahalingam Rajaseakaran , Han Leng , Waganer Eric J , Bhimaraj Arvind , Karmouty-quintana Harry , Guha Ashrith
Published: May 2021

Background:
Alternative cleavage and polyadenylation (APA) an emerging post-transcriptional mechanism for gene regulation that generates distinct isoforms of mRNA with different 3’UTR lengths. APA plays an important role in different biological processes and dysregulation of APA leading to many human diseases. However, the functional consequences of APA events in the right ventricle (RV) failure in humans remain unexplored.

Objective:
To identify whether the 3′UTR length is modulated by APA in the RV failure in humans compared to healthy RV.

Methods and Results:
We used Poly A tail RNA sequencing and a novel algorithm called DaPars to measure the global patterns of APA in healthy and failing human RV specimens. We revealed 3'UTR shortening and lengthening of many genes in failing RV compared to healthy RV specimens. The lengthened 3’UTR genes were enriched for functional groups such as RNA processing and splicing. Whereas the shortened 3’UTR genes were enriched for nucleic acid metabolic process and chromatin organization. In addition, differential APA events in RV failure regulates many pathways important for the progression of the RV failure. Finally, the regulator proteins of APA including cleavage and polyadenylation specificity factor (CPSF) 6 and 7, cleavage factor Im (CFIm) 25 and 59 have been regulated in RV failure compared to healthy RV specimens.

Conclusions:
Our results highlight important roles of APA in the progression of RV failure in humans, including RNA processing, splicing, and specific gene expression. Demonstrating that APA mediated 3’UTR length regulation provides the additional layer of gene expressions in RV failure.