bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10855: Cardiovascular Effectiveness of Empagliflozin Compared to Glucagon Like Peptide-1 Receptor Agonists and to Dipeptidyl Peptidase-4 Inhibitors in Older Patients: Results from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study
Authors: Htoo Phyo , Paik Julie , Tesfaye Helen , Schneeweiss Sebastian , Jawaid Dureshahwar , Wexler Deborah , Glynn Robert , Koeneman Lisette , Deruaz Luyet Anouk , Najafzadeh Mehdi , Patorno Elisabetta
Published: March 2022

The EMPA-REG OUTCOME trial showed cardioprotective effects of empagliflozin (EMPA) in patients with established cardiovascular diseases (CVD). Within the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) multi-database study of patients in routine care, we evaluated the relative cardiovascular benefits of EMPA versus therapeutic alternatives in older patients with type 2 diabetes (T2D) across the broad spectrum of cardiovascular risk. Using Medicare data (08/2014-09/2018), we identified 31,719 pairs of 1:1 propensity score-matched (PSM) T2D patients ≥65 years initiating EMPA or a GLP-1RA [Cohort 1], and 23,307 pairs initiating EMPA or a DPP-4i [Cohort 2]. We assessed (i) a modified major adverse cardiovascular event (MACE) outcome (MI, stroke, all-cause mortality) and (ii) hospitalization for heart failure (HHF) in primary discharge position. In each cohort, we estimated hazard ratios (HR) and rate differences (RD) per 1,000 person years of follow-up, adjusting for >140 baseline covariates and accounting for death as a competing risk, overall and in subgroups (i) with and (ii) without baseline CVD (that includes atherosclerotic CVD and HF). After PSM, exposure groups had similar characteristics (Table 1). Compared to GLP-1RA, EMPA had a similar risk of the modified MACE outcome [HR (95% CI): 1.05 (0.93,1.18)] and a reduced risk of HHF [HR 0.70 (0.57,0.86)]. Absolute benefit for HHF was larger in patients with CVD [RD -6.24 (-9.92, -2.56)] than in patients without CVD [RD -0.81 (-2.15, 0.54)]. Compared to DPP-4i, EMPA reduced the risk of both modified MACE outcome [HR: 0.67(0.59,0.77)] and HHF [HR: 0.46 (0.37,0.57)]. For both outcomes, the absolute benefit with EMPA was larger among patients with CVD compared to those without CVD. EMPA reduced the risk of HHF vs. GLP-1RA and DPP-4i and the risk of a modified MACE outcome vs. DPP-4i. The absolute benefit associated with EMPA was larger among patients with CVD compared to those without CVD.
Abstract 10857: Evaluating for Equity in a Safety Net Hospital: Socioeconomic Status, Adherence, and Outcomes in Cardiac Rehabilitation
Authors: Washington-plaskett Tulani , Gilman Joshua P , Wang Na , Zombeck Stephanie , Balady Gary
Published: March 2022

Objective:
To evaluate whether adherence and outcomes in cardiac rehabilitation are associated with socioeconomic status in a safety net hospital that provides care for a diverse patient population.

Introduction:
Uncovering the racial/ethnic health disparities that exist within cardiovascular medicine offers potential to mitigate treatment gaps that might affect outcomes. Since race is considered a social construct, socioeconomic status may be a more appropriate underlying factor to assess. The area deprivation index (ADI) reflects income, education, employment, and housing quality within a given 9-digit zip code. A higher ADI indicates more disadvantage (range 1-10).

Methods:
We identified 770 consecutive enrollees of the Cardiac Rehabilitation Program at Boston Medical Center from 2016-2020. The 9-digit zip codes of each enrollee were used to obtain their ADI. Associations between ADI and adherence (attending >70% of sessions) was evaluated while controlling for age, sex, race, education, diagnosis, smoking and transport times. Secondary outcomes included associations of ADI with change in exercise capacity, LDL cholesterol, weight, quality of life, nutrition, and depression scores.

Results:
Among 770 enrollees, 197 had missing covariates and 147 did not have a zip code with associated ADI, leaving 426 patients for analysis. Enrollees had a mean age of 59.8 years, 34% were female, 44% self-reported as black and 9% as Hispanic. The ADI for patients varied (mean =5; median =6) (
Figure 1
). The primary outcome adjusted for age, sex, race, education, diagnosis, smoking, and transport time, revealed no association for ADI with adherence to cardiac rehab (OR, 1.03 95% CI:0.99-1.07) or attendance rate (OR, 0.98 95% CI: 0.96-1.004). Secondary outcomes improved among patients regardless of ADI.

Conclusion:
In our safety net hospital that provides care without exception, we found equity in cardiac rehabilitation program outcomes despite socioeconomic status.
Abstract 10867: Two-Phase Nurse Navigator-Directed Transition-of-Care for Advanced Heart Failure During Index Hospitalization Reduces 30-Day Readmission Rates
Authors: Mitchel Hayley , Kozerski Alaxandra , Valenzuela Robert , Patalinghug Paul , Davidson Christine , Gopalan Radha
Published: March 2022

Introduction:
Heart failure (HF) is a leading cause of death in the US. Its management costs over $30 billion annually, and 65% is due to HF hospitalizations. In 2012 the Centers for Medicare and Medicaid Services instituted the Hospital Readmissions Reduction Program, designed to reduce cost burden by penalizing hospitals with readmission rates >20%. Current average 30-day readmission rates are estimated to be approximately 20-23%. We conducted a retrospective analysis of 30-day readmission rates of HF patients at a quaternary medical center, under management of a novel RN navigator (RNN) transition-of-care strategy.

Methods:
Transition-of-care was conducted in two phases: inpatient education and outpatient rapid follow-up (Table 1). Education focused on essential HF knowledge and its significance to the patient’s morbidity/mortality. Notes were recorded on a white board in the patient’s room during phase 1 to allow for daily review throughout the hospitalization. Phase 2 follow-up call was made within 48hrs of discharge.

Data was collected on patients hospitalized at Banner University Medical Center Phoenix from 4/2020-12/2020 with a primary diagnosis of decompensated HF, excluding those with durable mechanical circulatory support. The average time spent educating patients during phase I was adaptive based on patients’ comprehension of the material, and 30-day all-cause readmission was recorded.

Results:
A total of 233 patients were analyzed, and each patient received an estimated average of 90 minutes of inpatient education. Re-hospitalization within 30 days of discharge occurred in 12 patients (5.15%).

Conclusions:
In this analysis we report a 30-day readmission rate in HF patients from a single center that is remarkably lower than the national average. This was achieved via a 2-phase RNN transition-of-care strategy during index hospitalization. Primary limitation is the retrospective nature of the analysis in a single-center cohort.
Abstract 10878: New Bleeding Risk Prediction Model for Patients with Atrial Fibrillation on Direct Oral Anticoagulants
Authors: Tanaka Yoshihiro , Lancki Nicola , Khan Sadiya , Martin Karlyn , Passman Rod S
Published: March 2022

Introduction:
Although several risk scores exist to predict major bleeding events (MBEs) in patients with atrial fibrillation (AF) on anticoagulation therapy, most were derived from warfarin treated patients. Therefore, we sought to develop a new bleeding risk score specifically for AF patients on direct oral anticoagulants (DOAC).

Hypothesis:
A DOAC-specific risk prediction model will have good discrimination and calibration for 1-year and 3-year MBEs.

Methods:
AF patients aged ≥ 18 years on DOAC therapy who had at least 12-month follow-up between 2010 and 2017 were extracted from the Northwestern Medicine EHR. The primary endpoint was MBE defined by the International Society on Thrombosis and Hemostasis (ISTH) criteria. Seventy percent of patients were randomly assigned to a derivation cohort and the rest of 30% was used as an internal validation cohort. In the derivation cohort, all significant univariate predictors (p < 0.05) were incorporated into a multivariate Cox proportional hazard model. Harrel’s c-statistics was used for discrimination and Hosmer-Lemeshow test for calibration.

Results:
A total of 7,642 patients with AF on DOAC (Apixaban 43.9%, Rivaroxaban 36.4%, Edoxaban 0.1%, Dabigatran 19.5%) were analyzed (mean age, 69 ± 12 years: men, 59.5%: non-Hispanic White, 85.8%). During a median follow-up period of 3.3 years (interquartile range 2.0-5.0), 1,283 MBEs (922 in derivation cohort and 361 in validation cohort) were observed. Final model involved age, race, body mass index in addition to all components of CHA
2
DS
2
-Vasc score. Calibration plots at 1 year and 3 years looked good fit and Hosmer-Lemeshow test was not statistically significant. C-statistics of the new model at 1 year and 3 years were 0.70 (95% CI: 0.67 - 0.72) and 0.67 (95% CI: 0.65 - 0.69), both of which were higher than the reported c-statistics from HAS-BLED score. In the validation cohort, we observed the same significant differences in c-statistics at both years.

Conclusions:
A DOAC-specific risk prediction score had good model performance to quantify bleeding risk in patients with AF on DOAC.
Abstract 10879: Risk of Cardiac-Specific Mortality Among Ovarian Cancer Survivors: A Population-Based Study
Authors: Heaton Joseph , Mutema Motisola , Malouf Christina W , Trotman Sherlene
Published: March 2022

Background:
Ovarian cancer ranks as the fifth deadliest cancer among women and the top cause of female reproductive cancers. Studies identifying the consequences of treatment modalities are not well defined in the literature. We aim to compare the cardio-oncologic effect of therapy amongst ovarian cancer survivors.

Methods:
Data on patients diagnosed with ovarian cancer between 2000 and 2016 was extracted from the Surveillance, Epidemiology and End Results (SEER) registry. Patients were included when greater than 18 years of age at diagnosis and survival was 60 months or greater.

Results:
A total of 27,003 cancer patients were identified from the SEER registry. At diagnosis, the mean age was 55.6 ± 14.1 years; approximately 29.6% presented with localized cancer, 29.2% with regional cancer, and 37.3% with distant cancer. Overall, the median cardiac-specific survival time was 100 months compared to 80 months due to the primary cancer (log rank P < 0.001). Survival estimates are plotted in Figure 1. Ten-, and fifteen-year cardiac-specific survival for ovarian cancer was 82%, and 24%, respectively. Adjusted Cox proportional hazard models revealed an increased cardiac-specific mortality when using chemotherapy alone [HR 2.210, 95% CI 1.851 to 2.640, P < 0.001] and with any chemotherapy use [HR 1.937, 95% CI 1.841 to 2.037, P < 0.001]. Decreased cardiac-specific mortality was noted with surgery alone [HR 0.526, 95% CI 0.459 to 0.603, P < 0.001] and with combination surgery and radiation [HR 0.612, 95% CI 0.408 to 0.918, P = 0.18].

Conclusion:
Survivors of ovarian cancer are burdened by cardiac sequelae. The median survival time was twenty months greater for cardiac-specific mortality than the primary cancer. Death risk from diseases of the heart was significantly increased for patients receiving chemotherapy.

Figure 1. Kaplan-Meier Survival EstimatesEstimated survival times by diseases of heart, primary cancer, and all other causes of death.
Abstract 10882: Validation of a Continuous Flow Pressure Gradient for Coarctation Severity Assessment
Authors: Ghorbannia Arash , Ellepola Chalani D , Woods Ronald K , LaDisa John F
Published: March 2022

Introduction:
Coarctation of the aorta (CoA) severity is assessed via trans-CoA blood pressure gradient (BPG) estimated using simplified Bernoulli equation (SBE) with indices from noninvasive Doppler echocardiography (echo). However, simplifications of the SBE and inconsistent readings through a suboptimal insonation window limit diagnostic accuracy (DA). In a rabbit model mimicking human CoA (Fig. 1A), catheter
vs.
Doppler comparison of BPG revealed diastolic continuous-flow pressure gradient (CFPG) was independently associated with severity. We therefore hypothesized the unique properties of CFPG would improve DA in humans.

Methods:
SBE and CFPG were quantified using color flow Doppler in humans and rabbits with discrete non-recurrent CoA before repair (Fig. 1B). Quantifications used peak velocity proximal to (V
p
) and at the CoA (V
pk
), early diastolic velocity (V
d
), doppler velocity index (DVI), and normalized diastolic pressure half-time (dPHT; see Fig. 1B and C for definitions). Results were compared with measured BPG in rabbits (peak-to-peak catheter BPG) and humans (upper-lower extremity BPG). There was a total of 18 human and 26 rabbit cases; significance was defined a priori as a BPG of ≥20 mmHg. A CFPG ≥4 mmHg threshold was identified by maximizing sensitivity plus specificity in receiver operative curves (ROC).

Results:
Accuracy measures (Fig. 1D) revealed the superior performance of CFPG
vs.
SBE. Although reports suggest <60% of measured BPG can be explained with SBE, CFPG yielded a specificity of 78% in humans. Similar improvements were observed in rabbits. Results confirm the potential DA of CFPG in echo-based CoA assessment.

Fig. 1- (A) MRI confirming morphological similarities between rabbit and human CoA, (B) Spectral Doppler images show diastolic continuous flow, (C) indices derived from the generalized Bernoulli equation assuming exponential diastolic pressure loss, (D) diagnostic performance for CFPG
vs.
conventional SBE.
Abstract 10883: Cardiac-Oncology Prognostication and Outcomes in Female Breast Cancer Survivors
Authors: Heaton Joseph , Salanga Alyssa , Massaro Robert , Graebe Robert S
Published: March 2022

Background:
Heart disease risk and mortality is increased in breast cancer patients. Tumor and treatment factors have not been well described for cardiac mortality prognostication. We evaluated presenting characteristics and treatment factors on cardiac mortality in breast cancer survivors.

Methods:
The Surveillance, Epidemiology and End Results (SEER) registry was queried for adult female patients with malignant breast cancer from 1990-2016, who survived more than 60 months.

Results:
The SEER registry identified 686,559 patients. The average patient was white (83.3%), married (58.0%), and 59.9 ± 13.3 years. The typical tumor on presentation was moderately differentiated (38.7%), localized (55.2%), ER positive (71.2%), PR positive (60.3%), and HER status unknown (87.0%). Median survival times for cardiac-specific mortality was 117 months compared to 98 months for recurring breast cancer (log rank P < 0.001). Adjusted Cox proportional hazard models in Table 1 revealed increased cardiac-specific mortality with HER positive status and increasing age. Decreased mortality was noted in married or widowed patients and after selected multimodal therapies. Race, tumor grade, and localization were not well correlated.

Conclusion:
Breast cancer survivors are at risk for heart disease and cardiac mortality. After five years, the initial tumor burden does not correlate well with cardiac outcomes. Multimodal therapy and marriage were associated with significantly reduced risk.

Table 1. Cox Proportional Hazards

Hazard ratios for cardiac-specific mortality.
Abstract 10884: B-Cell-Mediated Sodium and Water Retention Contributes to Heart Failure Pathogenesis
Authors: Dingwell Luke S , Alibhai Faisal , Chiu Felix , Khan Saad , Wang Tao , Momen Abdul , Zhou Annie , Winer Daniel A , Robbins Clint S , Li Renke , Husain Mansoor
Published: March 2022

Background:
B-cells have been shown to serve pathogenic roles in heart failure through cardiac-specific monocyte mobilization and autoantibody deposition. Beyond this, we recently showed that mice with hypomorphic c-Myb activity (

c-myb
h/h

) have reduced B-cells and that B-cell deficiency is associated with increased sodium- and water-excretion and reduced blood pressure. Here, we determine the relevance of these responses in an experimental model of heart failure.

Methods & Results:
C57BL/6J wild-type (WT) and B-cell deficient

c-myb
h/h

mice (male and female; aged 10-12 weeks) underwent either: (i) permanent LAD ligation to induce myocardial infarction (MI); or (ii) sham surgery. Echocardiography showed that B-cell deficiency preserved ejection fraction (53±2 vs. 44±2 %; N=6-7/group; P<0.01) and limited pathologic remodeling with reduced LVID (end-diastolic: 4.9±0.1 vs. 5.5±0.1 mm; N=6-7/group; P<0.01; end-systolic: 3.8±0.2 vs. 4.5±0.1 mm; N=6-7/group; P<0.001) at 4-weeks post-MI compared to WT. Heart weight/tibia length and right lung weight/tibia length ratios (g/mm; P<0.01), as well as pleural effusion volumes (μl; P<0.05) were increased post-MI in WT, rather than

c-myb
h/h

mice. Indeed, mice with B-cell deficiency manifest reduced right lung weight/tibia length ratio (0.005±0.000 vs. 0.009±0.001 g/mm; N=5-6/group; P<0.01) and pleural effusion volume (17±6 vs. 55±18 μl; N=6-7/group; P<0.06) post-MI compared to WT. Underlying this decongestion, metabolic cage studies revealed that B-cell deficient mice had sustained increases in 24-h urine volume/body weight and 24-h sodium excretion/body weight ratios, which correlated with ejection fraction 4-weeks post-MI (r=0.53; N=13 pairs; P<0.05; and r=0.50; N=13 pairs; P<0.05, respectively).

Conclusion:
Together, these data show that B-cells play a role in sodium- and water-retention, and consequently, extracellular fluid volume expansion and congestion post-MI, and suggest that B-cells may represent a therapeutic target in heart failure.
Abstract 10887: The Under-Representation of Blacks, Females and Elderly in Randomized Controlled Trials of Heart Failure with Preserved Ejection Fraction: Meta-Analyses of Randomized Controlled Trials and Observational Studies
Authors: Khayyat Ibrahim , Khayyat Hani , HUYNH Thao
Published: March 2022

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is particularly prevalent in Blacks, women and elderly. Paradoxically, these patients are generally under-represented in randomized controlled trials (RCTs). We aim to compare the representation of Blacks, females and elderly in RCTs and observational studies of HFpEF therapies. Our secondary objective was to evaluate the secular trends of enrollment of these populations in the RCTs of HFpEF.

Methods:
We conducted a comprehensive database search of PubMed and EMBASE to identify HFpEF RCTs and HFpEF observational studies. Two independent readers extracted data on the proportions of Blacks, females and the mean age of patients enrolled in these studies. We compared the weighted means of age, proportions of blacks and proportions of females in the RCTs to those of observational studies. We divided the RCTs in three groups (enrollment prior to 2010, 2010-2015 and 2015 to 2020). Finally, we ascertained the secular trend of enrollment of Blacks, females and mean age of patients in the RCTs.

Results:
Our search yielded 17 RCTs and 9 observational studies. The trials included a total of 19,432 patients. There were marked under-enrollment of Blacks and females in the RCTs compared to the observational studies (Table 1). Furthermore, the weighted mean age of patients with HFpEF was also lower than that in the observational studies. From 1997-2020, the enrollment of females and elderly have increased, however, the enrollment of Blacks remained low in the RCTs of HFpEF.

Conclusions:
Blacks, women and elderly remain underrepresented in RCTs of HFpEF. Future RCTs of HFpEF should aim to enroll more Blacks, females and elderly so that the benefits of novel therapies can be validated in these special populations with high prevalence of HFpEF.
Abstract 10890: Microbial Community Structure of Dental Plaque, Blood and Cerebral Thrombus in Patients with Acute Ischemic Stroke
Authors: Li Mengzhen , Xiao Bin , Qiao Hanzi , Wu Bin , Yang Jiecong , Guo Qihua , Gong Baoying , Li Ying , Guo Jianwen
Published: March 2022

Introduction:
Epidemiological investigations have demonstrated a strong link between periodontal disease and stroke. However, relevant microbiological researches are still lacking at present. This study aimed to investigate the microbial composition of dental plaque, blood and cerebral thrombus in patients with acute ischemic stroke (AIS).

Hypothesis:
We hypothesized that there was a possible translocation for oral bacteria from periodontal pocket into blood and subsequently involving in the process of cerebral thrombus formation.

Methods:
Thrombus aspirates, dental plaque and venous blood samples were taken from 13 patients (11 males, 65.5 ± 10.7 years) with AIS. Microbiota was analyzed using high-throughput 16S rRNA gene amplicon sequencing and bioinformatics analyses.

Results:
Proteobacteria
was the most predominant phylum in dental plaque, blood and thrombus. There were no statistic difference in alpha (Shannon and Simpson indexes) and beta diversity (weighted UniFrac distance metric) among dental plaque, blood and thrombus, suggesting a high similarity in their microbial compositions. While, an increased trend of species diversity from supragingival plaque, subgingival plaque, blood to thrombus was observed. Besides, several microbes in thrombus were found to be correlated with plasma coagulation levels, including genera
Porphyromonas
, which is the common cause of periodontal infection. SourceTracker analysis suggested that about 58% microbial population in blood were oral origin and about 75% microbial population in cerebral thrombi were blood origin.

Conclusions:
This study described the bacterial profile of dental plaque, blood and thrombus in AIS patients. Our study suggested that some of the bacteria in cerebral thrombus might be derived from the blood and oral cavity and there was a close microbial community compositional relationship among these samples.
Abstract 10892: Cross-Cultural Validation and Psychometric Testing of the Heart Failure Somatic Perception Scale in Japan
Authors: HAYASHI KANAKO , Okada Akiko , Jurgens Corrine Y , Ito Shinya , Tsuchihashi-makaya Miyuki
Published: March 2022

Background:
The assessment of symptoms experienced by patients with heart failure (HF) has important contextual implications for self-care and allows for early recognition of signs of worsening HF. The Heart Failure Somatic Perception Scale (HFSPS) is a measurement tool developed in the U.S. to assess symptoms experienced by patients with HF, but it is expected to be applicable to patients in countries with different cultural backgrounds.

Objectives:
To evaluate the psychometric properties (validity and reliability) of the HFSPS in Japanese HF patients.

Methods:
This study assessed the factor structure of the HFSPS using confirmatory factor analysis in 320 HF outpatients in Japan. Criterion-related validity of the HFSPS was evaluated by correlating its factor scores with Patient-Reported Outcomes Measurement Information System (PROMIS) scores using Pearson's correlation coefficient. Internal consistency reliability of the HFSPS was evaluated using the factor score coefficient of determination, Cronbach's alpha, and the model-based internal consistency index.

Results:
The sample (n=320) was 72% male, mean age 72.9±12.8 years. Confirmatory factor analysis examining the four-factor structure of the HFSPS (dyspnea, chest discomfort, early and subtle, and edema), resulted in resulted in the following fit indices: χ2= (129, N=310), P<0.001, comparative fit index =0.825, Tucker-Lewis index =0.793, root mean square error of approximation =0.131. For criterion-related validity, all domains of the PROMIS items (physical health, mental health, global health, and social role satisfaction) were negatively correlated (-0.07 to -0.37) and statistically significant indicating higher symptom burden was associated with worse global health. HFSPS reliability resulted in Cronbach's alpha 0.878 for dyspnea, 0.607 for chest discomfort, 0.772 for early and subtle, 0.777 for edema, and 0.921 for the entire scale.

Conclusion:
This study suggests the HFSPS is a reliable and valid tool among Japanese with HF. Using this scale will provide accurate assessment of symptoms experienced by HF patients in research testing educational interventions to improve HF symptom recognition and response.
Abstract 10895: Biomarkers of Physical Frailty in Heart Failure
Authors: Denfeld Quin E , Purnell Jonathan Q , Lee Christopher S , Camacho Samuel A , Roberts Davis Mary , Hiatt Shirin O , Winters-Stone Kerri , Woodward William R , Habecker Beth A
Published: March 2022

Introduction:
Physical frailty is highly prevalent and associated with worse outcomes among adults with heart failure (HF). However, the biological mechanisms underlying physical frailty in HF are poorly understood. The aim was to identify biomarkers associated with physical frailty in HF using a multimarker strategy to reflect multiple physiological processes.

Hypothesis:
We hypothesized that biomarkers of neurohormonal activation, inflammation, insulin resistance, and adipose and skeletal muscle dysfunction would differentiate physically frail from non-physically frail adults with HF.

Methods:
We collected data and plasma samples from adults with New York Heart Association Functional Class I-IV HF. Physical frailty was measured with the Frailty Phenotype Criteria. Plasma biomarkers assayed were: N-terminal pro-B-type natriuretic peptide, norepinephrine, dihydroxyphenolglycol, soluble tumor necrosis factor alpha receptor 1, adiponectin, insulin, glucose, insulin-like growth factor-1, and myostatin. Comparative statistics and multivariate linear regression were used.

Results:
The average age of the participants (n = 113) was 63.5±15.7 years, half (48%) were women, and most had a non-ischemic etiology of HF (73%). Physical frailty was identified in 42% of the sample and associated with female gender, higher body mass index, more comorbidities, and HF with preserved ejection fraction. After adjusting for Seattle HF Model projected survival scores, comorbidities, body mass index, and gender, those physically frail had significantly lower plasma adiponectin, lower insulin-like growth factor-1, and lower myostatin compared with those non-physically frail (all
p
< 0.05). There were no significant differences in other biomarkers between physical frailty groups.

Conclusions:
Biomarkers involved in adipose tissue and skeletal muscle development, maintenance, and function were significantly different between those physically frail and non-physically frail. Physical frailty in HF may be, in part, underpinned by dysfunctional peripheral processes involving the adipose tissue and skeletal muscle.
Abstract 10901: Association of Fried's Frailty Score and Sarcopenia with Outcomes After Left Ventricular Assist Device Implantation
Authors: Dharmavaram Gourisree , Lin Andrew , Hannsun Gemmy , Nguyen Vuong , Sirignano Michelle , Mendenhall Maggie , Adler Eric D , Pretorius Victor , Tran Hao
Published: March 2022

Introduction:
Measures of frailty are predictive of morbidity and mortality in patients with left ventricular assist device (LVAD) placement. While Fried’s Frailty Assessment (FFA) is well-validated, sarcopenia has emerged as a powerful predictor. The additive value of sarcopenia to existing frailty assessments and its association with outcomes in patients undergoing LVAD implantation is not well-characterized.

Hypothesis:
We assessed the hypothesis that sarcopenia in addition to FFA improves the assessment of frailty and that patients identified as frail may experience worse outcomes after LVAD implantation.

Methods:
We evaluated 34 patients who underwent LVAD implantation at our medical center between January 2018 and December 2020. Perioperative FFA score ≥ 3 was defined as frail. Skeletal muscle indices were measured using perioperative computed tomography imaging of the psoas and pectoralis major and minor muscles areas. Sarcopenia was defined per the lowest skeletal muscle tertile with total psoas area index ≤4.45 and pectoralis muscle index ≤4.50.

Results:
Of the 34 patients who had LVAD placement, 12 received HeartWare HVAD and 22 received HeartMate III. Five patients met criteria for frailty based on FFA. When combined with frailty based on sarcopenia, 13 additional patients met criteria. There were no differences in age (57 vs 54.5 years, p = 0.49) or gender (89% vs 100% male, p = 0.62) between the frail and non-frail groups. On Kaplan-Meier analysis, the frail group had significantly higher rates of composite outcome of 30-day readmission and all-cause mortality (log-rank p = 0.027), (Figure 1). There was no difference in rates of transplantation.

Conclusions:
In conclusion, FFA is a commonly used tool for assessing frailty in patients with heart failure. The addition of sarcopenia assessment allows for higher sensitivity in identifying patients with frailty who are at risk for poor outcomes. Larger studies are needed to validate these findings.
Abstract 10903: Cardiovascular Morbidity Associated with Monoclonal Gammopathy of Undetermined Significance - A Danish Nationwide Study
Authors: Schwartz Brian , Schou Morten , Ruberg Frederick , Rucker Dane , Choi Jihoon , Siddiqi Omar , Kober Lars , Gislason Gunnar , Torp-Pedersen Christian , Andersson Charlotte
Published: March 2022

Introduction:
Case reports and smaller observational studies have suggested an association between monoclonal gammopathy of undetermined significance (MGUS) and various cardiovascular diseases. We aimed to explore the association of MGUS with a broad spectrum of incident cardiovascular disease further, using the Danish nationwide administrative databases.

Methods:
Between 1995-2018, all patients eighteen years and older with MGUS were matched (10:1) with controls from the general population based on age and sex. Patients with a diagnosis of multiple myeloma were excluded. Incident cardiovascular diseases were identified using ICD coding. Hazard ratios for cardiovascular outcomes were calculated using Cox proportional hazard regression.

Results:
Patients with MGUS (n= 8,445, mean age 69.9 years, 51.3% male) had a higher risk of developing most cardiovascular diseases after multivariable adjustment, including heart failure (HR 1.65, 95% CI 1.51-1.81), atrial fibrillation (HR 1.47, 95% CI 1.37-1.58), acute myocardial infarction (HR 1.24, 95% CI 1.08- 1.43), stroke (HR 1.25, 95% CI 1.12-1.40), aortic aneurysm (HR 1.49, 95% CI 1.23-1.80), aortic stenosis (HR 1.72, 95% CI 1.52-1.96), aortic regurgitation (HR 1.70, 95% CI 1.36-2.12), conduction disease (HR 1.52, 95% CI 1.25-1.82), pericarditis (HR 1.62, 95% CI 1.03-2.55), peripheral arterial disease (HR 1.86, 95% CI 1.61-2.14), cor pulmonale (HR 2.32, 95% CI 1.76-3.06), venous thromboembolism (HR 1.29, 95% CI 1.12-1.48), and implantation of a cardiac pacemaker or defibrillator (HR 1.34, 95% CI 1.14-1.59).

Conclusions:
MGUS is associated with a broad spectrum of cardiovascular diseases, with somewhat greater risk estimates observed for cardiovascular disorders that have previously been associated with infiltrative diseases (such as heart failure, pulmonary hypertension, aortic valvular disease, atrial fibrillation, and conduction abnormality) than for atherosclerotic and thrombotic disorders. Further studies are warranted to understand the underlying mechanisms.
Abstract 10905: Breast Arterial Calcification as a Novel Predictor of Cardiovascular Disease Risk: A Systematic Review and Meta-Analysis
Authors: Nerlekar Nitesh , Goel Vinay , Spear Ella , Cameron William , Thakur Udit , Chan Jasmine , Sultana Nushrat , Haseeb Anisha , Brown Adam , Nolan Mark , Nicholls Stephen , Marwick Thomas
Published: March 2022

Introduction:
Mammographically detected breast arterial calcification (BAC) is purported as a surrogate marker for cardiovascular disease (CVD). We conducted a systematic review and meta-analysis to determine the prevalence of BAC and its association with CVD risk and disease.

Methods:
Online databases were searched until March 2021 for studies reporting BAC. Four endpoints were evaluated: (1) BAC prevalence, (2) association with CVD risk factors, (3) prevalent and incident vascular disease and (4) BAC prevalence based on estimated CVD risk. Random-effects models were used. Data was analysed as odds ratio (OR), hazard ratio (HR) or effect size (ES) obtained through data transformation for differentially reported data. A CVD-specific risk metric was calculated as the product of CVD risk factor proportion and HR risk estimate from the CAD Consortium Risk Calculator and summed for all risk factors. Meta-regression modelling with predicted BAC prevalence stratified by age was performed.

Results:
There were 77 studies (104,710 patients) included. Pooled BAC prevalence was 22% (95%CI: 19-25%) with cumulatively increasing prevalence annually. Significant BAC predictors were age, hypertension, diabetes, hypercholesterolemia (p<0.01). BAC was associated with CAD (OR 2.65, 95%CI: 2.17-3.23, p<0.01) and non-coronary vascular disease (ES 0.80, 95%CI: 0.51-1.09, p<0.01). BAC associated with incident cardiovascular events (HR 1.61, 95%CI: 1.11-2.32, p=0.001). Predicted BAC prevalence associated significantly with increasing CVD risk regardless of age (Figure).

Conclusions:
BAC is significantly associated with prevalent and incident vascular disease affecting intimal and medial arterial beds. BAC is highly prevalent and associated with CVD risk factors individually and cumulatively. Routine assessment of BAC should be considered in screening mammography to potentially trigger CVD risk consultation.
Abstract 10909: Purulent Pericarditis Can Be Near Fatal
Authors: Balasubramanian Senthil S , Gaznabi Safwan , Krause Philip , Harris Jordan , Qamar Arman , Gordon Robert , Mishkel Gregory
Published: March 2022

A previously healthy 27 years-old male presented with 2 weeks of substernal chest pain, progressive dyspnea, palpitations, dizziness, and(&) fever. On exam, he had tachypnea & tachycardia, was hypotensive with an elevated JVP & muffled heart sounds. Labs showed elevated WBC, CRP, lactate & high sensitive troponin. Negative for COVID-19, flu. EKG showed sinus tachycardia. CT showed large pericardial effusion with gas in the pericardial space. Echo (Figure 1) revealed large pericardial effusion with tamponade. Emergent pericardiocentesis was performed draining a liter of straw-colored thick fluid (fluid: serum LDH >3) (Figure 2). Cultures grew Strep. Anginosus & Propionibacterium acnes. Extensive infectious & immunological workup returned negative. He had initially improved on broad-spectrum antibiotics however declined clinically on day 5. Repeat CT (Figures 3 & 4) showed recurrent pericardial effusion & mediastinal abscess with trace extravasation of contrast from the esophagus to posterior mediastinum. We present a case of esophageal perforation leading to Pyopneumopericardium. Stephenson et al. reported a case series of 13 patients with esophagopericardial fistulas & pyopneumopericardium with a 100% mortality rate. Another case series showed survival rates of only 17% in 60 patients with pyopneumopericardium secondary to esophageal perforation. Erosion of esophageal ulcers, ingestion of foreign body, iatrogenic, trauma, malignancy, localized inflammation can lead to esophageal perforation. Streptococcus pneumoniae & Staphylococcus aureus are common pathogens involved. Constrictive pericarditis is a possible complication in up to 20 to 30%. Our patient underwent pericardial window & surgical debridement followed by EGD-guided gastro-jejunal tube placement. He did well after 4 weeks of IV antibiotics. Our case demonstrates that early recognition & intervention can favorably alter the course of this potentially fatal cardiac condition.
Abstract 10912: Sarpogrelate, an Antiplatelet Agent, Suppressed Cardiac Hypertrophy and Systolic Dysfunction in a 5-ht
2a
Receptor-Independent Manner
Authors: Shimizu Kana , Funamoto Masafumi , Sunagawa Yoichi , Katanasaka Yasufumi , Miyazaki Yusuke , Shimizu Satoshi , Murai Noriyuki , Hasegawa Koji , Morimoto Tatsuya
Published: March 2022

Introduction:
Recently, the cost of new drug development is increasing year by year, and drug repositioning is being used as a strategy for developing new treatments by saving time and costs. We used a library of approved drugs to screen for compounds that suppress cardiomyocyte hypertrophy and identified the antiplatelet drug sarpogrelate, a selective serotonin-2A receptor antagonist, as a candidate for heart failure therapy. In this study, we investigated the effect of sarpogrelate on cultured cardiomyocyte hypertrophy and development of heart failure.

Methods & Results:
First, primary cultured cardiomyocytes were treated with 1 μM sarpogrelate and then stimulated with various hypertrophic stimuli (30 μM phenylephrine (PE), 0.1 μM angiotensin II and 0.1 μM endothelin 1). Sarpogrelate repressed hypertrophic responses induced by each stimulus, such as myofibrillar organization and increase in cell size. Moreover, PE-induced transactivation of the hypertrophic response genes promoter was significantly inhibited by sarpogrelate. Western blotting (WB) showed that sarpogrelate significantly suppressed PE-induced the phosphorylation of ERK1/2 and GATA4. Next, C57BL/6j male mice were subjected to a transverse aortic constriction (TAC) and sham operation. One day after the operation, the mice were randomly divided into 3 groups: sarpogrelate at 1 mg/kg or 5 mg/kg, and vehicle as a control. Daily oral administration was repeated for 8 weeks. Echocardiographic analysis showed that 5 mg/kg sarpogrelate significantly prevented a TAC-induced increase in posterior left ventricular wall thickness and a decrease in fractional shortening at 8 weeks after the operation. Five mg/kg sarpogrelate also suppressed a TAC-induced increase in HW/BW ratio, myocardial cell diameter, perivascular fibrosis, and mRNA levels of ANF and BNP. Moreover, the WB analysis showed that 5 mg/kg sarpogrelate significantly suppressed TAC-induced phosphorylation of the ERK1/2 and GATA4.

Conclusions:
Sarpogrelate significantly suppresses cardiomyocyte hypertrophy and the development of heart failure via at least, in part, by inhibition of ERK1/2-GATA4 pathway. These findings suggest that sarpogrelate may be an effective agent for heart failure therapy.
Abstract 10914: Refining Genotype-Phenotype Correlations for Post-Mortem Genetic Testing of Sudden Cardiac Death: From the POST SCD Study
Authors: Cheung Christopher C , Wojciak Julianne , Tanel Meghan , Connolly Andrew , Devine W. Patrick , Moffatt Ellen , Tseng Zian H
Published: March 2022

Introduction:
The POST SCD (POstmortem Systematic InvesTigation of Sudden Cardiac Death) Study is the only prospective unbiased sudden cardiac death (SCD) cohort to use comprehensive postmortem investigation to refine the SCD phenotype to true cardiac and arrhythmic causes. Most postmortem genetic testing focuses on genotypes while tolerating a SCD phenotype that is presumed cardiac.

Hypothesis:
We hypothesize that a comprehensive postmortem evaluation following presumed SCD will refine genotype-phenotype associations and interpretation of postmortem genetic testing.

Methods:
The POST SCD study prospectively identified all deaths attributed to out-of-hospital cardiac arrest between 18-90 years of age in San Francisco County between February 2011-March 2014 (20,440 deaths reviewed). Medical record review identified 525 presumed SCDs that met World Health Organization criteria. Comprehensive autopsy, toxicology, and histology ruled out non-arrhythmic causes (overdose, hemorrhage, PE) to arrive at 293 sudden arrhythmic deaths (SADs). In the first 30 SADs with high suspicion for heritable cause, a comprehensive 300-gene cardiac/arrhythmia panel was performed, then whole exome testing in cases with negative or non-contributory panel.

Results:
By pathologic criteria, the 30 autopsy-defined SADs (21 males [70%], median age 53 years) for genetic testing included dilated cardiomyopathy (37%), hypertrophic cardiomyopathy (HCM; 10%), hypertrophy without pathologic features of HCM (33%), primary electrical disease (10%), arrhythmogenic cardiomyopathy (3%), mitral valve prolapse (3%), or non-compaction (3%). In 3 SADs, we identified 4 pathogenic/likely pathogenic (P/LP) variants in
APOB
,
MYBPC3
,
GAA
, and
TTN
, but 3 of 4 (
APOB, GAA
,
TTN
) were non-contributory to SCD. There were 61 variants of uncertain significance in 24 patients (80%). Further exome testing in 7 SADs identified no compelling variants.

Conclusions:
Postmortem genetic testing identified P/LP variants in 10% of autopsy-proven SADs with high suspicion for heritable cause, but detailed postmortem phenotyping excluded 75% as non-contributory to SCD. These results highlight the importance of comprehensive autopsy evaluation to refine genotype-phenotype correlations.
Abstract 10915: Unappreciated Mechanisms of Fatty Acid Uptake in the Kidney: Fatty Acids Are Taken Up from Both Basolateral and Apical Side
Authors: Kawakami Ryo , Hanaoka Hirofumi , Kanai Ayaka , Obinata Hideru , Matsui Miki , Sunaga Hiroaki , Matsui Hiroki , Koitabashi Norimichi , Yokoyama Tomoyuki , Kurabayashi Masahiko , Iso Tatsuya
Published: March 2022

Introduction:
The kidney combusts a large amount of fatty acid (FA) for body fluid homeostasis. Despite the high demand for FA, however, little is known about the mechanisms of FA uptake. We aimed to determine how FAs are taken up by tubular epithelial cells.

Methods and Results:
Immunohistochemistry showed that CD36, known as an important FA transporter in the heart, was also expressed in the basolateral side of proximal tubule epithelial cells (PTECs). The uptake of
125
I-BMIPP, radio-labeled FA tracer, was significantly reduced in the kidney in CD36 knockout mice 1 min after its injection compared with wild-type mice, while the significant difference disappeared 30 min after the injection. In vivo imaging with two-photon microscopy revealed that BODIPY-C
12
, fluorescence-labeled FA tracer, was accumulated in the basolateral side (blood side) of PTECs shortly after its injection, which was followed by accumulation in the apical side (primary urine side), suggesting bidirectional FA uptake by PTECs. A large amount of neutral lipid was accumulated in the kidney when serum FA concentration was increased by accelerated lipolysis by administration of a β3 adrenergic receptor agonist. Immunofluorescence with cell-specific antibodies revealed that the cells with the most abundant lipid accumulation were PTECs, followed by tubular epithelial cells of the distal nephron. In addition, neutral lipid accumulation was enhanced even in the distal nephron when PTECs were injured with administrations of diphtheria toxin (DT) in mice overexpressing DT-receptor in a PTEC-specific manner. Importantly, the PTEC-injured mice exhibited marked albuminuria, suggesting disturbance of protein reabsorption. Despite marked albuminuria, however, urinary FA was not detected at all, suggesting complete FA reabsorption independently of albumin reabsorption in the kidney.

Conclusions:
Our results revealed the unique and prominent capability of proximal and distal tubular epithelial cells to take up FA from both blood (CD36-dependent) and primary urine (CD36-independent) and to store them as neutral lipids. We further suggest that the kidney acts not only as FA consuming tissue but also as FA keeping tissue to completely reabsorb FA from primary urine for unwasted energy use.
Abstract 10917: Dna Damage Promotes Atherosclerosis by Enhancing Inflammatory Responses via the DNA Sensing Cgas-Sting Pathway
Authors: SAKAI CHIEMI , Ishida Mari , Ueda Keitaro , Kobayashi Yusuke , Yoshizumi Masao , Ishida Takafumi
Published: March 2022

DNA damage is likely a key contributor to atherosclerosis. However, causative links between DNA damage and atherosclerosis are yet to be established. We investigated the role of DNA damage accumulation in atherosclerosis using the DNA repair protein Ku80-deficient apolipoprotein E knockout mice (

Ku80
+/-
ApoE

-/-
).

Ku80
+/-
ApoE

-/-

mice and
ApoE
-/-
mice were fed on high-fat diet for 4 weeks. Oil red O staining showed that plaque area was significantly increased in

Ku80
+/-
ApoE

-/-

aortas. Immunohistochemical analysis of lesions from

Ku80
+/-
ApoE

-/-

mice revealed enhanced accumulation of DNA double-strand breaks (DSBs). Similar results were obtained from

Ku80
+/-
ApoE

-/-

mice fed on high-fat diet for 2 weeks which was considered as the early stages of atherosclerosis. mRNA levels of inflammatory cytokines such as IL-6, MCP-1 and IFN-β in the aorta were significantly elevated in

Ku80
+/-
ApoE

-/-

mice than those of
ApoE

-/-

control mice. To further investigate links between DSB accumulation and enhanced proinflammatory responses, vascular smooth muscle cells were isolated from
Ku80
WT
(WT) and
Ku80

+/-

mice. mRNA levels of IL-6, MCP-1 and IFN-β were significantly elevated in
Ku80

+/-

cells compared to those of WT cells. Immunofluorescent analysis revealed DSB accumulation and persistent activation of the DNA repair kinase ATM in
Ku80

+/-

cells. In addition, senescent markers such as p16
INK4A
and senescence-associated β-gal activity were also upregulated in
Ku80

+/-

cells. Interestingly, the level of cytosolic DNA was elevated in
Ku80

+/-

cells. Furthermore, phosphorylation of TANK-binding kinase 1 was significantly increased in
Ku80

+/-

cells, indicating the activation of the cGAS-STING DNA sensing pathway. Thus, we performed cGAS or STING silencing in
Ku80

+/-

cells using siRNA to test whether cGAS-STING pathway was associated with enhanced proinflammatory responses. cGAS or STING silencing attenuated mRNA level of IL-6 and protein level of IκBα, the NFκB inhibitory protein.

Taken together, these results suggested that the accumulation of DSBs promoted atherosclerosis partly through enhanced inflammatory responses via the cGAS-STING activation. Therefore, cGAS-STING may be a promising target for therapeutic intervention of atherosclerosis.
Abstract 10918: Use of Mobile Health Technology in the Assessment of Statin-Associated Muscle Symptoms (SAMS)
Authors: Silverman-Lloyd Luke G , Sathiyakumar Vasanth , Huynh Pauline , Chang Blair , Martin Seth S
Published: March 2022

Background:
Statins are the cornerstone pharmacotherapy for lowering LDL-C and reducing risk of ASCVD. However, statin initiation and adherence are limited by statin-associated muscle symptoms (SAMS), posing significant clinical and public health dilemmas. Mobile health (mHealth) tools offer novel ways to assess real-time symptom data and share them back with patients to facilitate shared decision-making.

Objective:
To assess the feasibility and usability of an automated, text-message-based SAMS symptom-tracking platform to longitudinally track SAMS in patients who previously experienced muscle symptoms while on statin therapy.

Methods:
We enrolled 19 patients from 2 clinics at a single health system (Johns Hopkins; Baltimore, MD) and recorded baseline demographics, statin history and indication, perceptions of SAMS, and technology use via an online survey. Quantitative SAMS scores were gathered via daily text messages, and qualitative symptom data were collected in weekly text messages. Monthly symptom reports were sent to select participants via email on study days 30, 60 and 90. Upon study completion, participants reported perceptions of the study, the mHealth platform, and study measures via an online exit survey.

Results:
A total of 18 patients (aged 59.3 [SD 14.5] years, 67% women) collected data, and 15 patients completed the 90-day study protocol. Overall response rate to text messages was 91.5% (92.2% for daily SAMS messages, 86.0% for weekly muscle symptom prompts). Patients reported a statin adherence of 70%. Nine patients reported intolerable muscle symptoms at least once during the study, and intolerable symptom scores represented 3% of all reported symptom scores. Patients reported overall satisfaction with the study and found the SAMS scores helpful.

Conclusions:
Patients with previously reported SAMS successfully engaged with a text-message-based symptom-tracking platform with high interactivity and acceptability. This study demonstrates the feasibility and usability of an automated mHealth platform for longitudinally tracking SAMS in patients on statin therapy, and may provide a means for improving shared decision making to tailor statin therapy and improve adherence.