bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15970: Risk of Heart Failure Preserved Ejection Fraction in Obstructive Sleep Apnea: A Single Center Retrospective Analysis
Authors: Ebner Bertrand , Celli Diego , Karetnick Morgan , Olarte Neal , Byer Marina D , Maning Jennifer , Acuna Morin Edgar , Kapoor Kunal , Mehta Vijay , Ashinne Beteal , Zablah Gerardo , Gomez Camilo A , de Marchena Eduardo
Published: May 2021

Background:
Inherent characteristics of patients with Obstructive Sleep Apnea (OSA), such as age, obesity, diabetes and hypertension increase the risk for cardiovascular diseases including heart failure (HF). Herein, we sought to elucidate if there is an increased likelihood of having heart failure with preserved ejection fraction (HFpEF) as OSA severity increases. Furthermore, we correlated a validated H2FpEF score system in this cohort with clinical and imaging findings for HFpEF.

Results:
Out of 585 charts reviewed from patients diagnosed with OSA, a total of 108 patients with a concomitant transthoracic echocardiogram (TTE) and electrocardiogram performed were identified. The median age was 59 years old with 55.6% being males and Hispanic predominance 64.5%. The comorbidities found in our cohort involved hypertension (63.9%), diabetes mellitus (30.6%), coronary artery disease (15.7%), HF (13%), atrial fibrillation (8.3%), and stroke (7.4%). Mean BMI was 32.48 kg/m
2
and average neck size 16.02 inches. TTE findings demonstrated an average ejection fraction of 58±7% and mean pulmonary artery systolic pressure of 24±10 mmHg. OSA severity distribution is shown in Table 1. No significant association was found between grade of severity of OSA with clinical diagnosis of HF, nor with diastolic dysfunction by TTE. The average probability of HFpEF by validated score was 50%, and the distribution of the score was the same across severity of OSA (p=0.260). Pearson’s correlation showed a significant positive relationship between age, BMI and PASP, and H2FpEF score (p<0.01 for all), however, no relation was found when correlating with neck size, apnea-hypopnea index and mean oxygen saturation.

Conclusion:
Although patients with OSA might have a higher H2FpEF score due to inherent characteristics, the clinical diagnosis of HFpEF in our population was lower than expected by H2FpEF score, in which the degree of severity was not associated with a higher H2FpEF score.
Abstract 15971: Gender, Race, and Age Specific Baseline Predictors of All-Cause Mortality in BARI2D Trial Identified by Machine Learning
Authors: Mallick Zyannah , Mahmood Nayab , Dandi Gauri , Haq Nowreen , Banerjee Avantika , Atkinson Ian , Gani Nuha , Xin Victoria , Hayashi Scout , Lewis Natalie , Qureshi Khizar , Hasan Noah , Dey Amit , Husain Anwar , Rosenberg Yves D , Hasan Ahmed A
Published: May 2021

Introduction:
NHLBI supported Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes trial (BARI2D) (NCT00006305) evaluated patients with type 2 diabetes and coronary artery disease. Primary trial analysis found no significant differences in rates of all-cause mortality (ACM) among patients who underwent 1) prompt revascularization with medical therapy versus aggressive medical therapy alone and 2) insulin-sensitization medical strategies versus insulin-provision. We reused publicly available individual patient-level data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analysis by machine learning (ML), using random survival forest (RSF) to identify gender, race, and age specific baseline predictors for ACM.

Methods:
The total 2368 trial participants was separated into several subgroups based on gender (female and male), age (40-49, 50-59, 60-69, 70-80), and race (Non-Hispanic White, Hispanic White, Non-Hispanic Non-White, and Hispanic Non-White). RSF was performed on 84 baseline variables to identify predictors of the primary outcome, ACM. The top 10 predictors for each subgroup were tested in a Cox proportional hazards model

Results:
Top 10 predictors of ACM are shown in Table 1. Although anticipated cardiovascular (CV) and diabetic predictors appeared among the top predictors, at the same time, renal function biomarkers like serum creatinine, urine albumin/creatinine ratio, and serum potassium uniquely showed among the top 5 predictors across the gender, age, and race specific subgroups.

Conclusions:
Using ML, we uncovered in an unbiased fashion, gender, race and age groups specific unanticipated top baseline predictors of ACM in BARI2D trial. This highlights the value of gender, race and age groups specific predictors of outcomes for determining the efficacy of therapeutic interventions and help advance precision medicine.
Abstract 15978: Acetyl-coa Catalysis by Atp-citrate Lyase is Essential for Myofibroblast Differentiation and Persistence
Authors: Lazaropoulos Michael P , Gibb Andrew A , Huynh Anh , Wellen Kathryn , Elrod John W
Published: May 2021

A feature of heart failure (HF) is excessive extracellular matrix deposition and cardiac remodeling by a differentiated fibroblast population known as myofibroblasts. Identifying mechanisms of myofibroblast differentiation in cardiac fibrosis could yield novel therapeutic targets to delay or reverse HF. Recent evidence suggests that myofibroblast differentiation requires metabolic reprogramming for transcriptional activation of the myofibroblast gene program by chromatin-dependent mechanisms. We previously reported that inhibition of histone demethylation blocks myofibroblast formation, however, whether histone acetylation (e.g., H3K27ac, a prominent mark associated with gene transcription) is involved in fibroblast reprogramming remains unclear. ATP-citrate lyase (ACLY) synthesizes acetyl-CoA and therein supplies acetyl-CoA to the nucleus, where it is used as a substrate by histone acetyltransferases (HATs). To define the role of acetyl-CoA metabolism in myofibroblast differentiation, we stimulated differentiation in mouse embryonic fibroblasts (MEFs) and adult mouse cardiac fibroblasts (ACFs) with the pro-fibrotic agonist transforming growth factor β (TGFβ) and treated cells with a pharmacological inhibitor of ACLY. ACLY inhibition decreased myofibroblast gene expression in ACF and MEFs in TGFβ-stimulated myofibroblast differentiation, in addition to decreasing the population of αSMA positive MEFs. Genetic deletion of ACLY in MEFs recapitulated the results observed with pharmacological inhibition. Encouragingly, the ACLY inhibitor was sufficient to revert fully differentiated myofibroblasts under continuous TGFβ stimulation to a quiescent, non-fibrotic phenotype. Altogether, our data indicate that ACLY activity is necessary for myofibroblast differentiation and persistence. We hypothesize that ACLY-dependent acetyl-CoA synthesis is necessary for histone acetylation and transcriptional activation of the myofibroblast gene program. Currently, we are examining mechanisms of ACLY-dependent chromatin remodeling in fibroblasts and the
in vivo
relevance of this mechanism in mutant mice. In summary, ACLY is a potential target to reverse cardiac fibrosis and lessen HF.
Abstract 15979: Utility of Post-extraction Follow-up Blood Cultures in Patients With Cardiovascular Implantable Electronic Device Infection
Authors: khalil sarwat , Esquer Garrigos Zerelda , Challener Douglas W , Gurram Pooja , Tariq Wajeeha , CastilloAlmeida Natalia , Baddour Larry M , DeSimone Daniel C , Wilson Walter R , Lahr Brian D , Sohail M Rizwan R
Published: May 2021

Introduction:
Cardiovascular implantable electronic devices (CIED) infections are frequently complicated with bloodstream infection (BSI). Complete device removal and prolonged antimicrobial therapy is essential for cure. The frequency of persistent BSI after source control (device extraction) is not well described. This study aims to assess the utility of repeat blood cultures (BC) after device extraction as recommended by the American Heart Association (AHA) guidelines.

Methods:
We selected patients who presented with BSI in the setting of CIED infection and underwent device removal at Mayo Clinic Rochester between 2012 and 2017. Cases where BC were not drawn prior to extraction, or repeated within 72 hours of device extraction, or met criteria for contamination were excluded.

Results:
Of 656 patients who underwent CIED extraction for device infection, 190 with post-extraction BC met study criteria. Among the final study cohort (Table 1), 159 patients had negative BC, while 31 had positive BC following CIED extraction. Pre-extraction, the most common causative organism was
Staphylococcus aureus
(91/190, 48%) (Figure 1a). Post-extraction, 22 of the 31 (71%) cases of persistent BSI were due to
S. aureus
(Fig 1b). The median duration of BSI was not significantly different between negative and positive BC groups (3 versus 4 days, p=0.92).

Conclusions:
Majority of patients had resolution of BSI after CIED extraction.
S. aureus
was the most common cause of persistent BSI post-extraction. Our findings support the AHA guidelines of repeating BC after device extraction, especially for
S aureus
.
Abstract 15983: New Left Ventricular Systolic Dysfunction in Hospitalized Patients With Covid-19
Authors: Witting Celeste S , Baman Jayson , Cantey Eric , Cheema Baljash , Nishtala Arvind , Akhter Nausheen , Flaherty James
Published: May 2021

Introduction:
Left ventricular systolic dysfunction (LVSD) has been observed in COVID-19 and is thought to be multifactorial. The epidemiology of stress cardiomyopathy in these patients has not been studied.

Methods:
Transthoracic echocardiograms (TTE) were evaluated in consecutive COVID-19 patients admitted to a large tertiary care center in Chicago, Illinois. Subjects with new LVEF ≤50% with prior normal LVEF or unknown baseline LVEF were compared to those with LVEF >50% or previously known LVSD. InterTAK scores were calculated for all patients with new LVSD, and a cutoff of 50 was used to delineate the likelihood of stress-induced cardiomyopathy. Two-tailed student t-test of unequal variance and Chi-squared testing were used for analysis of continuous and categorical variables, respectively, with p<0.05 considered statistically significant.

Results:
Of hospitalized patients with COVID-19 (n=982), 231 (23.5%) underwent TTE. Thirty patients (13.0%) were found to have new LVSD. Patients with new LVSD had higher peak troponin and rates of ICU admission and incidence of in-hospital mortality compared to patients without new LVSD (Table). Ten patients (33%) with new LVSD had InterTAK scores ≥50. Compared to those with low InterTAK scores, these patients were more likely to be female, have lower peak d-dimer, and a trend towards lower troponin as well as rates of ICU admission and mortality. Only two patients with new LV dysfunction were noted to have Takotsubo patterns on TTE.

Conclusions:
In hospitalized patients with COVID-19, new LVSD was rare but associated with an increased risk of critical illness requiring intensive care, intubation and in-hospital mortality. The etiology of new LVSD in COVID-19 is likely multifactorial, but those with LV dysfunction likely secondary to stress-induced cardiomyopathy have a trend towards improved mortality.
Abstract 15988: Heart Failure Group Medical Visits to Improve Quality of Life: A Feasibility Study
Authors: Rajendran Iniya , Williams Patricia , McGregor Pei-Chun
Published: May 2021

Introduction:
Group Medical Visits (GMV) are medical appointments where patients with similar medical conditions are seen in a group setting. Heart Failure (HF) is an ideal fit for the GMV model of healthcare delivery. HF guidelines emphasize the need for a self-care regimen including symptom knowledge, medication adherence, dietary and lifestyle modifications and social support. We conducted an intervention with these elements in a GMV setting to assess feasibility and improvement in quality of life (QoL).

Methods:
We enrolled a convenience sample of high-risk veterans with HF who required frequent follow up. Veterans participated in a longitudinal GMV for eight sessions lasting two hours each and occurring once a month. A curriculum was prepared a priori, and each session was led by an invited guest facilitator and focused on nutrition, exercise, stress, holistic health among others. Feasibility was assessed through recruitment and retention data. We also collected pre-post medication compliance data and QoL change using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). We gathered feedback after each session.

Results:
Twelve patients were invited to the program and nine patients attended the first session. The average attendance was 6 participants each week with 4 participants attending all eight sessions. All were men, 22% identified as Black and 8 of 9 participants had preserved ejection fraction and obesity. At baseline, the mean KCCQ was 49.2. At the end of the intervention, the mean change in KCCQ-12 score was +9 (p=0.39). The largest change (+12, p=0.13) was seen on the QoL subscale. No significant improvement was seen in medication compliance. Participants listed community building, peer to peer education, learning about hospital services and continued contact with their provider as highlights of the program. Due to invitation of high-risk individuals, we had one death and seven hospitalizations during the study period.

Conclusions:
Longitudinal GMVs for high risk patients has a role in HF education and management. It may improve QoL and provider-patient relationship. It is well accepted by the veteran population and has the potential to be routinely integrated into clinical practice.
Abstract 16002: Chronotropic Incompetence Limits Exercise Capacity in Patients Taking Beta-Blockers
Authors: Tysarowski Maciej , Smarz Krzysztof , Zaborska Beata , Pilichowska-Paszkiet Ewa , Sikora-Frac Malgorzata , Budaj Andrzej , Jaxa-Chamiec Tomasz
Published: May 2021

Introduction:
Chronotropic incompetence in patients taking beta-blockers is associated with poor prognosis; however, its impact on exercise capacity (EC) remains unclear.

Hypothesis:
We assessed the hypothesis that chronotropic incompetence is associated with decreased exercise capacity in patients taking beta-blockers.

Methods:
We retrospectively analyzed data from consecutive patients taking beta-blockers referred for cardiopulmonary exercise testing. EC was expressed as peak oxygen uptake (VO
2
peak; mL/kg/min). Chronotropic incompetence was defined as chronotropic index (CI) ≤ 62%. CI was calculated as [(HR at peak-resting HR) / (maximum predicted HR-resting HR)] х 100%.

Results:
Among 140 patients all taking beta-blockers (age 61 ± 9.7 years; 73% males), there were 113 (80.7%) patients with chronotropic incompetence. EC was lower in the group with chronotropic incompetence than the group without it, VO
2
peak 18.3 ± 5.7 vs. 24.0 ± 5.3 mL/kg/min, p < 0.001. In multivariate analysis (
Table
), EC correlated positively with CI (β = 0.14, p < 0.001) and male gender (β = 5.12, p < 0.001), and negatively with age (β = –0.17, p < 0.001) and presence of heart failure (β = –3.35, p < 0.001). Beta-blocker dose was not associated with EC. Partial correlation attributable to CI (partial R
2
= 24.7%) accounted for more than one-third of the variance in EC explained by the model (adjusted R
2
= 59.8%).

Conclusions:
In patients taking beta-blockers, the presence of chronotropic incompetence was associated with lower EC, regardless of the beta-blocker dose. CI accounted for more than one-third of EC variance explained by our model.
Abstract 16007: Myeloid-specific Deletion in Lipid Phosphate Phosphatase3 (plpp3) Increases Cardiac Inflammation
Authors: Tripathi Himi , Shindo Kazuhiro , Donahue Renee , Gao Erhe , Morris Andrew J , Smyth Susan S , Abdel-latif Ahmed
Published: May 2021

Introduction and Hypothesis:
Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide. The innate immune response plays a major role in cardiac remodeling after AMI. Lysophosphatidic acid (LPA), produced by autotaxin (ATX) and degraded by Lipid phosphate phosphatase 3 (LPP3), regulates monocytosis and promotes inflammation. However, the role of LPP3 in post-AMI inflammation is not understood. Here, we investigated the possible role of Myeloid-specific Plpp3 KO mice in cardiac and systemic inflammation and resulting in adverse cardiac remodeling post-MI.

Methods and Results:
To generate mice with Myeloid-specific Plpp3 deletion
,
female Plpp3
fl/fl
mice were crossed to male Plpp3 mice expressing Cre recombinase under the control of the LysM promoter to generate lysm-plpp3. mice. These mice and their littermate control underwent MI or sham surgery. Inflammatory cell content was assessed using flow cytometry and immunohistochemistry. Cardiac function and scar size were assessed by echocardiography and Mason Trichrome staining, respectively. Increased number of Ly6C
hi
monocytes (CD45
+
/Ly6C/G
hi
/CD115
hi
) and pro-inflammatory macrophages (CD45
+
/F4-80
+
/CD11b
+
) (CD45
+
/F4-80
+
/CD86
+
), in cardiac tissue of Cre+LysM mice was observed compared to Cre-fl/fl littermate controls during peak post-MI inflammation, as assessed by flow cytometry (
Fig.1A-C
). This increase in inflammatory cells and inflammation may be the consequence of the significant increase in bone marrow and spleen progenitor cell count and proliferation. Moreover, Cre+LysM mice cardiac functional recovery was also reduced significantly (
Fig. 1D-F
) as assessed by echocardiography.

Conclusion:
Myeloid-specific Plpp3 deletion increases the deleterious effects of inflammation on the ischemic myocardium and ATX/ LPA signaling could represent a novel therapeutic target for future clinical studies of coronary heart diseases.
Abstract 16025: The Association of Cardiology Billing Patterns With Healthcare Utilization and Clinical Outcomes in Atrial Fibrillation Patients
Authors: Crystal Eugene , Kaoutskaia Anna , Ko Dennis T , Chu Cherry , Kaveh Shojania , Dorian Paul , Yu Bing , Shurrab Mohammed , Fang Jiming , Ross Heather , Peter Austin , Bouck Zachary , Goodman Shaun G , Bhatia Sacha
Published: May 2021

Introduction:
The relationship between health care utilization and clinical outcomes in patients (pts) with atrial fibrillation (AF) is unknown. The objective of this study was to investigate whether cardiologists’ billing patterns are associated with different patient-level clinical outcomes.

Methods:
A retrospective cohort study was conducted using claims data in Ontario, Canada between April 1, 2011 and March 31, 2016. This study included all cardiologists who had at least 25 AF pts per year, and whose billings were ≥80% fee-for service. The cardiologists were stratified into quintiles based on their median billing per patient over the study period. The primary outcomes were patient-level receipt of repeat visits, cardiac diagnostic tests, medications ≤1 year of index date. The secondary clinical outcomes were death, emergency department visits and all-cause hospitalization at 1 year post-index visit.

Results:
The patient cohort was comprised of 182,572 AF pts (median age 74 years, 58% male) from 467 cardiologists. AF pts seen by higher billing cardiologists were more likely to undergo diagnostic tests within the first year of the index visit. Pts were 26% more likely to have an echocardiogram (adjusted odds ratio [aOR] 1.26 [95% CI, 1.13 to 1.39]), 28% a stress test (aOR 1.28 [1.15-1.42]), 25% Holter monitoring (aOR 1.25 [1.10-1.40]), and 80% more likely to get a stress echocardiogram (aOR 1.80 [1.49-2.10]), highest vs quintile 2. (Figure). Pts across billing quintiles received similar medical therapy. AF pts seen by higher billing cardiologists had a higher rate of all-cause hospitalization (aOR 1.13 [1.07- 1.19]); mortality rates were similar across cardiologists billing quintiles (e.g., aOR 0.98 [0.91- 1.04] for quintile 4 vs 2).

Conclusion:
Cardiologists who bill more per patient tend to order more diagnostic tests per AF patient but these are not associated with lower rates of hospitalization or death.
Abstract 16051: Pattern and Behavior of Electrocardiographic Changes in Patients Undergoing Repair of Anomalous Aortic Origin of Coronary Arteries
Authors: Williams Stephen B , Doan Tam , Pham Tam Dan , Reaves Dana , Bonilla Carlos , Binsalamah Ziyad , McKenzie Emmett D , Caldarone Christopher , Molossi Silvana M
Published: May 2021

Introduction:
Surgical repair in anomalous aortic origin of a coronary artery (AAOCA) aims at mitigating the risk of sudden cardiac death in a subset of patients (pts). The pattern and behavior of electrocardiogram (ECG) changes in a large cohort of these pts is lacking. We aim to describe post-operative (post-op) ECG changes in this population with medium term follow up (f/u).

Methods:
Observational study evaluating ECGs before and after surgery to describe peri-operative changes through f/u. All patients <21 years (yrs) with AAOCA were prospectively evaluated and managed following a standardized approach from 12/2012-11/2019. A subset underwent repair given high-risk features. ECGs were reviewed at 5 specific time intervals from pre-operative (pre-op) to 90-day post-op f/u. Significant findings included new ST elevation (STE), T wave inversion (TWI) and/or new q waves.

Results:
A total of 64 pts were identified (median age 13.7 yrs, 64% male). Two patients had evidence of STE and TWI pre-op and were not included. Of 62 pts: 47 (75%) had new STE early post-op and all but 1 had resolution at 90-day f/u; 50 (81%) had no evidence of new TWI or q waves early post-op and 96% of these remained stable at 90-day f/u. Conversely, 12 (19%) had new TWI in the early post-op: 8 had isolated changes (75% resolved at 90 days) and 4 associated with new q waves (50% resolved at 90 days). Including all ECG changes in the total cohort, 92% resolved completely at 90-day f/u. In those pts (8%) with persistent changes, none required late reintervention and all but 1 were cleared for return to exercise. All patients were alive at medium f/u of 4 yrs (IQR 2-6) with normal ventricular function.

Conclusions:
New STE is a common finding in the early post-op period following repair of AAOCA and is not correlated with persistent ECG changes at 90-day follow up. TWI is infrequently seen but less likely to resolve if associated with new q waves. Despite these changes in the early post-op, clinical outcomes medium-term are excellent.
Abstract 16057: First-line Ablation of Ventricular Tachycardia in Ischemic Cardiomyopathy: Stratification of Outcomes by Left Ventricular Function
Authors: Briceno David , Romero Jorge , Patel Kavisha , Diaz Juan C , Alviz Isabella , Lakkireddy Dhanunjaya , Della Rocca Domenico G , Gopinathannair Rakesh , Natale Andrea , Di Biase Luigi
Published: May 2021

Introduction:
Randomized controlled trials (RCTs) have shown improved outcomes in patients undergoing first-line catheter ablation of ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with ischemic cardiomyopathy (ICM). Nonetheless, the impact of Left ventricular ejection fraction (LVEF) on the outcomes after catheter ablation (CA) have not been studied.

Hypothesis:
LVEF has a strong impact on the outcome after CA for VT in patients with ICM.

Methods:
RCTs evaluating first-line ablation versus medical therapy in patients with VT and ICM were included. Risk estimates and 95% confidence intervals (CI) were measured.

Results:
Four RCTs with a total of 505 patients (mean age 66 ± 9 years, 89% male, 80% with previous revascularization) were included. Mean LVEF was 35 ± 8%. At a mean follow-up of 24 ± 9 months, a significant benefit in survival-free from appropriate ICD therapies was observed in all patients undergoing first-line catheter ablation compared to medical management (RR 0.70, 95% CI 0.56-0.86). In patients with moderately depressed LVEF (>30-50%), first line VT ablation was associated with a statistically significant reduction in the composite endpoint of survival-free VT/VF and appropriate ICD therapies (HR: 0.52, 95% CI: 0.36-0.76), whereas there was no difference in patients with severely depressed LVEF (</=30%) (HR: 0.56, 95% CI: 0.24-1.32). Funnel plots did not show asymmetry suggesting lack of bias.

Conclusions:
Patients with ICM and VT undergoing first-line ablation have a significant lower rate of appropriate ICD therapies without a mortality difference compared to patients receiving an initial approach based on medical therapy. The beneficial effect was only observed in patients with moderately depressed LVEF (>30-50%).
Abstract 16058: Abnormal P Wave Morphology is Associated With Decreased Left Atrial Appendage Ejection Velocity
Authors: Mcconkey Nathaniel D , Malamas Peter , Plamenac Jovan , Park Robert , Weigel Frank , Gonzalez Mario , Naccarelli Gerald , Maheshwari Ankit
Published: May 2021

Introduction:
P-wave abnormalities measured during periods of sinus rhythm have been associated stroke in people with atrial fibrillation (AF). The majority of AF-related strokes occur from left atrial appendage (LAA) thromboembolism. Electrical and mechanical dysfunction of the left atrium (LA) and left atrial appendage (LAA) can lower the threshold for thromboembolism and stroke.

Hypothesis:
We aimed to determine whether P-wave abnormalities are associated with decreased LAA ejection velocity (LAAV) on transesophageal echocardiography (TEE).

Methods:
We conducted a retrospective cross-sectional study. We reviewed patients at a tertiary care medical center who had underwent TEE in sinus rhythm and had an interpretable sinus rhythm ECG within 12 months of TEE. Participants were excluded for history of complex congenital heart disease, age<18, cardiac transplantation, and atrial pacing. Logistic regression analysis was used to estimate the odds ratios of LAAV<40 cm/s for P-wave abnormalities—advanced interatrial block (aIAB), abnormal P-wave terminal force in V1 (aPTFV1), prolonged P-wave duration (PPWD), and abnormal P-wave axis (aPWA).

Results:
In our final cohort of 169 patients, the odds ratios of aIAB and aPTFV1 for LAAV<40 cm/s after adjustment for CHA
2
DS
2
VASc variables, heart rate during TEE, history of atrial arrhythmias, and left atrial volume index were 2.81 (1.07-7.53) and 2.48 (1.13-5.60), respectively.

Conclusions:
P-wave abnormalities are independently associated with low LAAV, which may explain their association with AF-related stroke. Further research is needed to determine if incorporation of P-wave analysis will aid AF-related stroke prediction algorithms.
Abstract 16063: Demographic Differences in the Burden of Heart Failure Attributable to Obesity-Associated Metabolic Risk Factors: The Atherosclerosis in Communities (ARIC) Study
Authors: Okyere Robert , Florido Roberta , Zhang Sui , Echouffo-Tcheugui Justin , Hamo Carine , Michos Erin D , NAMBI VIJAY , Post Wendy S , Gerstenblith Gary , Blumenthal Roger S , Ballantyne Christie M , Coresh Josef , Selvin Elizabeth , Ndumele Chiadi E
Published: May 2021

Background:
The development of metabolic syndrome (MetS) and diabetes among those with obesity varies by age, sex, race and socioeconomic status (SES) and is associated with increased heart failure (HF) risk. There are limited data about whether the HF burden related to these metabolic risk factors differs across demographic groups.

Hypothesis:
There is significant variation in the proportion of HF events attributable to obesity-associated metabolic risk factors across demographic groups.

Methods:
We studied 10,133 white and black participants at ARIC Visit 4 (1996-98) without baseline HF. Age was categorized as < or ≥65 yrs and SES categorized as low, medium or high based on education, income, and area deprivation index. MetS was defined by AHA/NHLBI criteria. HF follow-up was through 2018. Individuals with obesity (BMI ≥30kg/m
2
) were grouped as: no MetS or diabetes, MetS alone, or both MetS and diabetes (highest metabolic risk). Across demographic strata, we assessed: metabolic risk group prevalences; hazard ratios (HRs) for HF associated with each metabolic risk group (Cox regression); and the population attributable risk (PAR) for HF associated with metabolic risk factors in those with obesity.

Results:
Those with age ≥65, male sex, black race and low SES were more likely to be in the highest metabolic risk group (
Table
). Over 20 years (N= 2,194 events), compared to normal weight without MetS or diabetes, the highest metabolic risk was associated with 3-5 fold higher HF risk in all subgroups. Stronger HF associations were seen for those < vs ≥65 years (p interaction <0.001) and for women vs men (p interaction 0.03). The PAR for obesity-associated metabolic risk factors varied by race (39 vs 32% for blacks vs whites) and SES (40 vs 28% for low vs high SES).

Conclusion:
There are important demographic differences in the burden of HF related to metabolic risk factors. Addressing disparities in the HF impact of metabolic risk factors is critical to efforts to improve health equity.
Abstract 16069: Molecular Dynamics Simulations Reveal the Functional Impact of Pathogenic Variants in the LDL Receptor LA 4-6 Repeats
Authors: James Jose , Kullo Iftikhar J
Published: May 2021

Introduction:
Functional annotation of rare variants is key to the implementation of genomic medicine. We used molecular dynamics (MD) simulations to assess functional consequences of putative pathogenic variants (PVs) in the low-density lipoprotein receptor gene (
LDLR
). LDLR has a multidomain structure with seven LA repeats and local interactions between these repeats influence ligand binding. However, binding and recycling of the receptor-ligand complex require global changes in conformation. Using MD, we investigated the effects of PVs on long-range dynamics and LDL binding.

Methods:
An LA 4-6 repeat structure was created from a crystal structure of the extracellular domain (PDB: 1N7D). Structures were solvated with a water box containing TIP3P water molecules and simulated using the AMBER software package with the ff14SB forcefield. The wild type (WT) structure was first relaxed using MD; and subsequently PVs D245Y, F181Y and F181G were modeled. Dynamics were simulated for approximately one microsecond. Values for LDL binding for each PV were obtained from a prior study which used a radioisotope uptake assay.

Results:
WT domains demonstrated a stable conformation based on root mean square deviation. PVs disrupted the normal distribution in all domains significantly (p < 0.0001), broadening it and introducing multiple peaks. Projection along the top principal components (PCs) showed global destabilization with all PVs. The variant with the greatest impact on LDL binding, F181G, adopted a distinct alternate conformation. Comparison between PV and WT subspaces from PCA correlated with LDL binding (R
2
= 0.99, exponential regression). Structural analysis revealed that the LA5 calcium cage is involved in inter-domain salt bridges, which are disrupted in simulations of PVs.

Conclusion:
MD simulation of LA4-6 repeats in LDLR suggests PVs alter long-range conformational dynamics, and that such dynamics correlate with LDL binding. The impact of PVs on conformational dynamics and binding may be through disruption of interdomain salt bridges that are mediated by the acidic calcium cage. This study demonstrates the potential utility of MD simulations to functionally characterize
LDLR
variants.
Abstract 16088: Mortality Trend Among Patients With Atrial Fibrillation on Long Term Anticoagulation Who Developed Intracranial Hemorrhage: Insights From the National Inpatient Database From 2006 to 2014
Authors: Quelal Karol , Torres Andrea , Torres Christian , Tafur Alfonso
Published: May 2021

Introduction:
Intracranial hemorrhage (ICH), is a potential complication of anticoagulation use in atrial fibrillation (AF). During the last decade, guidelines have evolved from recommending vitamin K antagonists to a preference for DOACs in the case of non-valvular AF after FDA approval in 2010. Data have reported that DOACs have a lower rate of ICH and an overall better clinical profile when compared to VKA.

Aim:
We sought to describe the rate of ICH and its associated mortality h with the increment in the use of DOACs over the period of 2006 to 2014 in the US population with AF.

Methods:
We queried the NIS database 2006-2014. AF patients, patients using long term anticoagulation, and intracranial hemorrhage admissions were selected using the appropriate ICD-9 codes. Time trend was analyzed using Chi-square. In-hospital mortality was evaluated by binomial logistic regression.

Results:
We found a 30740346 weighted population with AF between 2006 and 2014. 16.8 % were long term users of anticoagulants. Of them, 1.1% (n: 56400) were admitted due to ICH. Long term anticoagulation use in AF went from 13.3% in 2006 to 17.3% in 2010 (p<0.001). Among AF patients, 30.7% of patients had in-hospital death when admitted for ICH using long term anticoagulation. Long term anticoagulation was associated with increased in-hospital death in ICH patients aOR 1.31 (95% CI 1.24 - 1.39) when compared to those not using long term anticoagulation. Patients with AF and long term use of anticoagulants showed an increased frequency of in-hospital mortality from 32.7% in 2006 to 34.2% in 2007 and a decrease to 30.9% up to 2010. The decrease in mortality rate was more notorious from 2010 to 2014 going to 25.8% (p< 0.001).

Conclusions:
The rate of ICH diagnosis among anticoagulated atrial fibrillation patients has remained stable after the introduction of DOACs. Rates of inpatient death have decreased from 2006 to 2014 having the most notorious inflection point in 2010 after the progressive introduction of DOACs .
Abstract 16091: Cardiac Mechanical Determinants of Exercise Function in Differing Fontan Heart Failure Phenotypes
Authors: Chowdhury Shahryar M , taylor carolyn , ATZ Andrew M
Published: May 2021

Introduction:
The objective of this study was to investigate the association of contractility, afterload, and diastolic dysfunction to exercise function between patients with heart failure and preserved ejection fraction (HFpEF) versus heart failure with reduced ejection fraction (HFrEF).

Hypothesis:
Cardiac mechanical determinants of exercise would be different in HFrEF versus HFpEF

Methods:
Core-lab echocardiograms were obtained from the publically-available Pediatric Heart Network Fontan Cross-sectional Study database. Ejection fraction was considered abnormal if < 50%. Diastolic function was defined as abnormal if the diastolic pressure:volume quotient (lateral E:e’/end-diastolic volume) was > 10
th
percentile. Patients were divided into three groups: 1 = normal EF and normal diastolic function, 2 = decreased EF with normal diastolic function (HFrEF), 3 = normal EF with abnormal diastolic function (HFpEF). End-systolic elastance (Ees), a measure of contractility, and arterial elastance (Ea), a measure of afterload, were calculated.

Results:
238 patients were included. Differences between groups are reported in the Table. In group 1, there were no significant correlations between exercise and echocardiographic measures. In patients with HFrEF, Ea was correlated with percent predicted max O
2
pulse (ppO
2
P-max) (r = -0.40, p = 0.03). In patients with HFpEF, lateral E:e’/EDV was correlated with ppO
2
P-max (r = -0.57, p = 0.02). No measures correlated with percent predicted peak VO
2
in either group.

Conclusions:
As Fontan patients progress to heart failure, stroke volume during exercise is limited by afterload in patients with HFrEF. Alternatively, stroke volume is limited by diastolic dysfunction in HFpEF patients. These measures of cardiac mechanics may be useful in identifying the mechanisms that drive exercise dysfunction in Fontan patients of varying heart failure phenotypes.
Abstract 16098: Additional Predictive Value of Plasma C24:0/C16:0 Ceramide, and Its Modulation by BMI, Over NT-proBNP in the Prediction of Mortality
Authors: Peterson Linda R , Cresci Sharon , Schaffer Jean E , Jiang Xuntian , Ory Daniel S , Vasan Ramachandran , Xanthakis Vanessa , Duncan Meredith S , Dorr Marcus , Gross Stefan
Published: May 2021

Introduction:
NT-proBNP is a predictor of mortality in patients with or without HF. Ceramides are bioactive lipids involved in cell signaling and membrane structure. Our group showed that the ratio of specific plasma ceramides (C24:0/C16:0) is
inversely
related to death. However, NT-proBNP levels were not available for multivariate modeling of mortality in that cohort.

Hypothesis:
We hypothesized that plasma C24:0/C16:0 would add to a predictive model that includes NT-proBNP and classical cardiovascular risk factors (CVRs) of mortality. We also hypothesized that body mass index (BMI) modulates the predictive value of plasma C24:0/C16:0.

Methods:
We performed multivariable modeling on data from 2,760 Caucasian subjects in the SHIP (Study of Health in Pomerania) cohort from northern Europe. Plasma C24:0/C16:0 was measured using targeted liquid chromatograph/tandem mass spectrometry. CVRs in the modeling included: age, sex, systolic blood pressure, current smoking, diabetes, and total/high-density cholesterol. Model performance was evaluated using Akaike’s information criterion (AIC) and Harrel’s c-statistic.

Results:
There were 529 deaths over a median of 14.6 y. Model selection via AIC revealed that the best model with the least number of variables to predict mortality included plasma C24:0/16:0 and BMI (+ their interaction), CVRs, and NT-proBNP, P < 0.001. The evidence ratio showed that this best model is 540 times more likely to be the ideal model than the model that only includes CVRs. The best model was also much more informative than a model that added only NT-proBNP to the CVRs (ΔAIC = 19.865, Akaike weight < 0.001). With increasing BMI, the protective effect of plasma C24:0/16:0 on survival probability diminished. Post hoc analysis showed the best model predicted CVD mortality but not non-CVD mortality.

Conclusions:
A mortality prediction model that includes plasma C24:0/C16:0, NT-proBNP, and CVRs is superior to CVRs alone or CVRs + NT-proBNP and helps further stratify patients’ risk. BMI modifies the predictive value of plasma C24:0/C16:0. Plasma C24:0/C16:0 may be a novel target for modifying CVD mortality risk.
Abstract 16100: Investigating the Risk of Cardiovascular Disease in Women Living With HIV: Perspectives From a Large Clinical Cohort in Miami, FL
Authors: Vincent Louis T , Ebner Bertrand , Grant Jelani , Loyd Quentin , Powell Alexis , Boulanger Catherine , Hurwitz Barry E , Martinez claudia
Published: May 2021

Background:
Cardiovascular disease (CVD) is the leading cause of death in persons living with HIV (PLWH). CVD risk in PLWH is often underestimated, and sex stratified analyses are lacking. We sought to investigate the prevalence of CVD and associated viremic and metabolic risk factors in a cohort of men and women living with HIV (MLWH and WLWH respectively).

Methods:
A retrospective chart review of PLWH seen at the University of Miami/Jackson Memorial Hospital outpatient HIV clinics between 2017-2019 was performed. Demographic, clinical, and laboratory data along with diagnostic studies were obtained from electronic health records.

Results:
A total of 985 patient charts were reviewed, among which 102 patients had one or more manifestations of CVD. Among WLWH and MLWH, overall prevalence of CVD was comparable (9.6% vs 11.0%, p=0.49). Compared to MLWH, WLWH had lower prevalence of atrial fibrillation (0.7% vs 2.2%, p=0.04) but comparable coronary artery disease, peripheral arterial disease, heart failure, and history of stroke or myocardial infarction. Among patients with CVD, WLWH and MLWH were similar in age (61.2±8.4 vs. 58.7±9.8 years, p=0.18) and had no significant differences in race or ethnicity. No differences were noted between genders in systolic blood pressure or LDL-C, although WLWH showed a trend of increased hemoglobin A1c (6.7±1.7 vs. 6.1±1.2, p=0.07), and BMI (29.9±7.6 vs. 27.3±6.2, p=0.06). Of note, WLWH had a higher average CD4 count compared to MLWH (613±335 vs 460±330 cells/mm
3
, p=0.01), but comparable antiretroviral therapy (ART) adherence (90.7% vs 84.7%, p=0.39), and presence of undetectable viral load (64.3% vs 67.2%, p=0.76). On multivariate logistic regression adjusted for age, race, viremia, and comorbidities, having diabetes was associated with increased CVD risk (OR=1.69, 95% CI [1.03-2.79], p=0.04). ART treatment was associated with decreased CVD risk (OR=0.30, 95% CI [0.14-0.65], p=0.002), while female gender was not (OR=0.76, 95% CI [0.48-1.20], p=0.24).

Conclusion:
Men and women living with HIV had comparable prevalence of CVD. This may be associated with a trend towards increased traditional risk factors among WLWH. Improving ART adherence and viremic control is vital to reducing CVD risk in this population.
Abstract 16107: Electrocardiographic Findings and Their Associations With Adverse Outcomes in Hospitalized Patients With COVID-19
Authors: Fatakdawala Mariya , Pang Jason , Patel Ritesh , Thannoun Tariq , Grable Cullen , Damaraju Sarita , Mawji Shamim B , Folivi Messan , Chauhan Siddharth , Powell Christopher , Shabbir Muhammad A , Lyubarova Radmila , Damaraju Srikanth , Palaskas Nicolas L , Deswal Anita M , Taegtmeyer Heinrich , Garcia-Sayan Enrique , Koutroumpakis Efstratios
Published: May 2021

Introduction:
Although primarily a respiratory illness, COVID-19 frequently involves the cardiovascular system.

Hypothesis:
Accordingly, we assessed whether abnormal electrocardiographic findings, including cardiac dysrhythmias, ST/T wave changes, and QTc interval prolongation, predict adverse outcomes in patients with COVID-19.

Methods:
A multi-center retrospective study of hospitalized patients with COVID-19 was performed across 4 hospitals in Texas and 1 in New York. Initial and subsequent ECG findings among patients with uncomplicated disease course, patients with adverse clinical outcomes (need for vasopressors, mechanical ventilation or renal replacement therapy) and patients who died were analyzed. Univariable and multivariable Cox analyses were performed.

Results:
We identified 297 consecutive patients with COVID-19. Of these patients, 91% had available ECGs. Median heart rate on initial ECG was 92 bpm (IQR: 27), and median QTc interval was 442 msec (IQR: 40). Longer QTc interval on initial ECG was associated with adverse clinical outcomes (443 msec, IQR: 43) and death (457 msec, IQR: 52, vs 441.5 msec, IQR: 36; p=0.033). Cardiac dysrhythmias or ST/T wave changes were noted in subsequent ECGs of 46% of patients and were associated with adverse clinical outcomes (58%) or death (68% vs 33%; HR: 2.2, 95% CI: 1.3-3.6; p=0.002). Sixty-four patients (23%) developed a QTc interval >500msec during their hospitalization. In multivariable Cox analysis, history of coronary artery disease was independently associated with development of QTc>500msec (HR 2.1, 95% CI 1.0-4.4; p=0.047) while other baseline comorbidities were not. Patients with QTc>500msec were more commonly treated with azithromycin (91% vs 77%; p=0.048); no other differences in COVID-19 treatment were identified. In-hospital mortality among patients with QTc>500msec was 37% versus 13% among patients with shorter QTc intervals (HR: 2.6, 95% CI 1.5-4.5; p=0.001).

Conclusions:
Prolonged QTc interval on initial ECG of COVID-19 patients predicted adverse outcomes and death. Azithromycin was associated with development of QTc>500msec. Patients with a QTc interval >500msec had a 2.6 times higher risk for in-hospital mortality compared to patients with shorter QTc intervals.
Abstract 16110: Impact of Institutional Volume on In-hospital Mortality and Resource Utilization Among Patients With Pulmonary Embolism Treated With Catheter Directed Thrombolysis: A Population-Based Cohort Study
Authors: Meier Isaac C , Hawkins Beau M , Silva Federico , ROUSAN TALLA , Edupuganti Mohan , Raskob Gary , Giri Jay S , Baber Usman
Published: May 2021

Introduction:
Catheter-directed thrombolysis (CDT) is an evolving percutaneous approach for the management of acute pulmonary embolism (PE). Contemporary data examining in-hospital outcomes in relation to procedural volume are limited.

Methods:
Data sets were extracted from the 2016 national readmission database. Using ICD 10 codes, a search was performed to identify all patients hospitalized with a primary or secondary diagnosis of PE who underwent CDT between 1/1/2016 and 12/31/2016. Hospitals were grouped into quartiles by CDT volume and rates of in-hospital mortality, length of stay, and cost were compared across groups. Adjusted associations were examined using multivariable logistic regression.

Results and Conclusions:
We identified 2,353 unique patients with PE who underwent CDT at 483 hospitals. The median (25th, 75th percentiles) number of CDT procedures per hospital was 3 (1, 6). Mortality rates were 11.4%, 5.3%, 5.6% and 3.8%, respectively, at hospitals in the 1st, 2nd, 3rd and 4th quartile of CDT procedural volume (Figure; p=0.001). Results were unchanged after multivariable adjustment. Median length of stay by quartile was as follows: 6.5, 5, 5, and 4 days (p <0.001). The median cost for the different quartiles was $28,277, $25,953, $25,896, and $23,007 (p <0.001). We found that CDT performed in patients with PE at low-volume hospitals is associated with excess mortality as well as increased length of stay and cost when compared with higher-volume centers. These findings may inform guidance for volume thresholds for utilization of CDT in the management of acute PE.
Abstract 16115: The Society of Cardiovascular Angiography and Interventions Cardiogenic Shock Classification Predicts Mortality in Cardiac Arrest Patients Prior to Pci
Authors: Ortiz Fernando , Stouffer George A , Rossi Joseph , Katz Jason N
Published: May 2021

Introduction:
Acute coronary syndrome (ACS) complicated by cardiac arrest (CA) has a heterogeneous presentation, and risk can be challenging to stratify. This study aimed to apply the SCAI cardiogenic shock stages to patients with ACS complicated by CA at early pivotal time intervals when prompt interventions may have a greater impact.

Methods:
Patients undergoing PCI presenting with CA were stratified according to the SCAI shock classification, retrospectively, on arrival to the cardiac catheterization laboratory (CCL) and on arrival to the intensive care unit (ICU). The primary end-point was in-hospital mortality. Secondary end-points were mortality stratified by the use of mechanical circulatory support or the level of vasopressor support used.

Results:
Between 01/2014 -08/2018, seventy-nine patients presented with ACS complicated by a CA. The mean age was 70 (SD ± 12) years, and 19 (24%) were females. On arrival to the CCL 17 (22%) were stage A, 6 (8%) were stage B, 31 (40%) were stage C, 19 (24%) were stage D, and 6 (8%) were stage E. In general, there was a stepwise increase in mortality with increasing stage (A 35% vs. B 16% vs. C 48% vs. D 68% vs. E 83%; p=0.05). There was a similar trend when stratified on arrival to the ICU (Figure 1), although of marginal statistical significance (P = 0.07). Presentation with shock stage D or E to the CCL was predictive of mortality (OR 3.7 CI 1.3-10.5; p=0.01) on logistic regression models. The use of mechanical support was not associated with increased mortality. However, the use of an Impella in patients requiring high vasopressor support at arrival to the CCL was associated with a trend towards decreased mortality (25% vs. 61%, p=0.18).

Conclusion:
Increasing SCAI shock stages on arrival to the CCL and ICU is associated with increased in-hospital mortality among patients who presented after a CA and underwent PCI. The SCAI classification at defined time points has the potential to serve as an important research tool.