bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13942: Down-titration of Renin-angiotensin System Inhibitors After Hospitalization for Heart Failure With Reduced Ejection Fraction
Authors: Goyal Parag , Chen Ligong , Rosenson Robert S , Umejiego John , Pontes-Arruda Alessandro , Levitan Emily B
Published: May 2021

Introduction:
While there are data demonstrating poor outcomes associated with discontinuation of renin-angiotensin system inhibitors (RASI) after hospitalization for heart failure with reduced ejection fraction (HFrEF), less is known about the prevalence and outcomes of RASI dose reduction.

Objective:
To determine the proportion of older US adults with HFrEF who had RASI down-titration after hospitalization and identify characteristics associated with RASI down-titration.

Methods:
This study included US Medicare beneficiaries age > 65 years with fee-for-service coverage hospitalized with HFrEF in 2007-2017 who filled a prescription for a RASI in the 90 days prior to hospitalization. We compared dosages of RASI prescription fills prior to and up to 1 year after hospitalization. Diagnoses of conditions that can reduce RASI tolerance (hypotension, acute kidney injury, hyperkalemia, angioedema, syncope, fall-related injuries) were identified during the hospitalization. We used modified Poisson models to calculate prevalence ratios and 95% CIs.

Results:
Among 35,047 Medicare beneficiaries hospitalized with HFrEF, the average age was 78.5 (SD 8.0) years, 82.3% were white, and 50.8% were women. After hospitalization, 61.9% filled a prescription for the same or higher dose, 15.6% filled a lower dose, and 22.6% did not fill a prescription for a RASI. Among the beneficiaries who filled a prescription for a RASI after hospitalization, hypotension, acute kidney injury, and hyperkalemia were associated with a higher prevalence of RASI down-titration (Table).

Conclusion:
Down-titration of RASIs is common among older adults with HFrEF following hospitalization and is more frequent among individuals with hypotension, acute kidney injury, or hyperkalemia during hospitalization. Down-titration may reduce risks of adverse events during periods of reduced medication tolerance after hospitalization, but could also lead to sustained suboptimal treatment.
Abstract 13951: Safety, Tolerability and Efficacy of Single-dose Amg 890, a Novel Sirna Targeting Lp(a), in Healthy Subjects and Subjects With Elevated Lp(a)
Authors: Koren Michael J , Moriarty Patrick M , Neutel Joel , Baum Seth J , Hernandez-Illas Martha , Weintraub Howard S , Hellawell Jennifer , Varrieur Tracy , Sohn Winnie , Wang Huei , Elliott-Davey Mary , Kassahun Helina , Watts Gerald F
Published: May 2021

Introduction:
Mendelian and epidemiological randomization studies have identified lipoprotein(a) [Lp(a)] as a risk factor for myocardial infarction and other atherosclerotic events. There are currently no approved medicines that selectively target Lp(a) and have demonstrated reduction in CV events. AMG 890 is a siRNA designed to reduce the production of Lp(a) by targeting mRNA transcribed from the LPA gene.

Methods:
This phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AMG 890. Adults with plasma concentrations of Lp(a) ≥ 70 to ≤ 199 nmol/L (cohorts 1-5), and ≥ 200 nmol/L (cohorts 6-7), were randomized 3:1 to receive a single subcutaneous dose of investigational product (IP; AMG 890 or placebo). The primary endpoints were treatment-emergent adverse events (TEAEs), safety laboratory analytes, vital signs and ECGs. Secondary endpoints included PK parameters and percent reduction from baseline in Lp(a).

Results:
64 subjects were administered IP (cohorts 1-5: AMG 890, n=30, doses: 3 mg, 9 mg, 30 mg, 75 mg, 225 mg; placebo, n=10; cohorts 6-7: AMG 890, n=18, doses: 9 mg and 75 mg; placebo, n=6). The most common TEAEs were headache (10% AMG 890; 25% placebo) and upper respiratory tract infection (15% AMG 890; 13% placebo); no safety concerns were identified for AMG 890. In cohorts 1-5, single doses of AMG 890 effectively reduced mean Lp(a) levels from baseline by 71-96% (based on doses) at Day 43, and by 80-94% at Day 113 (cohorts 2-5). In cohorts 6 and 7, single doses of AMG 890 effectively reduced mean Lp(a) levels from baseline by 75% and 89% at Day 43, respectively, and by 61% and 80% at Day 113, respectively.

Conclusions:
In adults with elevated Lp(a), single-dose treatment of AMG 890 was well-tolerated and significantly reduced Lp(a) with observed maximal percent reductions of > 90% and effects persisting for more than 6 months at doses of 9 mg or higher.
Abstract 14035: Renal Tubular Secretion and Cardiac Distribution of Dofetilide is Dependent on MATE1 Function
Authors: Uddin Muhammad Erfan , Jin Yan , Gibson Alice A , Bonilla Ingrid M , Carnes Cynthia A , Hu Shuiying , Sparreboom Alex
Published: May 2021

Introduction:
Dofetilide is a delayed rectifier potassium channel inhibitor used to treat patients with atrial fibrillation and flutter, and its use is associated with a risk of QT prolongation and
Torsades de Pointes
. The mechanisms involved in dofetilide’s renal tubular secretion and its uptake into cardiomyocytes remain unknown. Previously reported drug-drug interaction (DDI) studies suggest the involvement of organic cation transporters. Here, we investigated the contribution of organic cation transporters (OCT2 and MATE1) to the pharmacokinetics of dofetilide to gain insight into its DDI potential.

Hypothesis:
Based on known DDIs with dofetilide, we hypothesize that OCT2 and/or MATE1 play a key role in the inter-individual variability in pharmacokinetics and pharmacodynamics of dofetilide.

Methods:
In vitro
and
ex vivo
transport kinetics of dofetilide were determined in HEK293 cells stably transfected with OCT2 or MATE1, and in isolated cardiomyocytes, respectively.
In vivo
studies were performed in wild-type, OCT2-, and MATE1-deficient mice (n=5) receiving dofetilide (5 mg/kg, p.o., 2.5 mg/kg, i.v.), with or without several contraindicated drugs. Dofetilide concentrations in plasma and urine were determined by UPLC-MS/MS.

Results:
In vitro
studies demonstrated that dofetilide is a good substrate of MATE1 but not OCT2. Deficiency of MATE1 was associated with increased plasma concentrations of dofetilide and with a significantly reduced urinary excretion (3-fold in females and 5-fold in males, respectively). Dofetilide accumulation in cardiomyocytes was increased by 2-fold in MATE1-deficient females, and pre-incubation with the MATE1 inhibitor cimetidine significantly reduced dofetilide uptake in wild-type cardiomyocytes. Several contraindicated drugs listed in the dofetilide prescribing information, including cimetidine, ketoconazole, increased dofetilide plasma exposure in wild-type mice by >2.8-fold.

Conclusion:
Renal secretion of dofetilide is mediated by MATE1 and is highly sensitive to inhibition by many widely used prescription drugs that can cause clinically relevant DDIs. Deficiency of MATE1 also increases accumulation in the heart which may contribute to individual variation in response to dofetilide.
Abstract 14058: Sex-based Differences in Reported Payments to Cardiologists by Drug and Device Manufacturers
Authors: Shapero Kayle , Jelani Qurat-ul-ain , Kahn Peter
Published: May 2021

Introduction:
Sex-based disparities in salaries and promotion in cardiovascular medicine are well known, but there is little data on industry compensation by sex. We attempted to explore sex differences in financial ties to industry in the form of drug and device manufacturer payments to cardiologists.

Methods:
2018 Open Payments data was obtained from Centers for Medicare and Medicaid Services (CMS). A cross walk was used to link CMS National Plan and Provider Enumeration System National Provider Identifier Data with open payments data. Physician specialty (adult cardiology), sex, state of practice, number and amount of payments, drug and device information were obtained and aggregated for analysis using natural language processing.

Results:
In 2018, total of 879,119 payments were made to 29246 physicians (10.2% female), totaling $145,556,106. Nationwide, female cardiologists had lower rates of payments (15.5 payments per year vs 25.9 payments), lower average compensation per payment ($113 vs $169) when compared to their male counterparts. Analysis of five drugs/devices with the largest aggregated payments revealed that the female representation in certain categories (consulting, compensation for serving as speaker-non continuing education, and travel and lodging) was far lower than expected (3.8%, 5.4%, and 4.2% respectively).

Conclusions:
Female cardiologists received fewer payments and lower compensation per payment from drug and device manufacturers as compared to their male counterparts. Further studies are required to determine reasons behind differences in compensation and efforts be made to standardize compensation regardless of sex to promote equal opportunities for all physicians.
Abstract 14211: Positive Predictive Value of Troponin for NSTEMI Based on Chief Complaint
Authors: Kirkpatrick Scott , Hammes Andy , Rudofker Eric , Trent Stacy , Michael Sean , Levy Andrew
Published: May 2021

Introduction:
Serum troponin is a ubiquitous biomarker used to diagnose acute myocardial infarction (AMI). The positive predictive value (PPV) of high-sensitivity troponin for Type 1 Myocardial Infarction is approximately 15% in the United States, compared with 55% in Europe, a difference that may be explained by differences in patient selection for testing. Our objective was to examine test characteristics for contemporary troponin assays based on chief complaint in the Emergency Department (ED).

Methods:
In a retrospective cohort analysis, we examined all 30,833 encounters in which a troponin test was performed in any of the 14 emergency departments within a large integrated health system between 10/1/18 and 10/1/19. All hospitals used a contemporary cardiac troponin-I (cTnI) assay. We excluded patients with ST-segment elevation myocardial infarction (STEMI) since this diagnosis is made by electrocardiogram. We grouped patients by chief complaint (CC) and further stratified by pre-specified cTnI thresholds. Within each cTnI/CC category, we calculated the proportion of patients subsequently classified with a principal ICD-10 diagnosis of non-STEMI (NSTEMI).

Results:
For all patients selected for cTnI testing, 1.7% were diagnosed with NSTEMI. Overall, the PPV of cTnI for NSTEMI was 11%. This PPV for NSTEMI was highest among patients with chest pain (33%). Excluding patients with chest pain, the PPV for NSTEMI was 3.9%. For nearly all chief complaints, the PPV for NSTEMI increased with higher cTnI thresholds.

Conclusion:
In a large integrated health system, fewer than one in fifty patients undergoing cTnI testing in the ED were ultimately diagnosed with NSTEMI. The PPV of cTnI for NSTEMI was significantly higher among patients presenting with chest pain compared to other chief complaints. These data highlight the importance of selecting patients for testing and interpreting abnormalities in the context of presenting symptoms.
Abstract 14221: Right Ventricular Adaptation to Pressure Overload: Differences Between Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Arterial Hypertension
Authors: Braams Natalia J , van Leeuwen Joost W , vonk noordegraaf anton , Bogaard Harm Jan , Meijboom Lilian J , De Man Frances S
Published: May 2021

Background:
Chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH)) are both associated with right ventricular (RV) failure and death. Although both conditions develop in the pre-capillary pulmonary vasculature, patient characteristics are different. CTEPH patients are older, predominantly male and more often have a history of venous thromboembolism. Therefore, the RV might be affected differently in CTEPH compared to iPAH. We aimed to compare RV adaptation in CTEPH and iPAH.

Methods:
Between 2000 and 2019 all treatment naive iPAH and CTEPH patients diagnosed in the Amsterdam UMC were included if a right heart catheterization and cardiac magnetic resonance imaging (CMR) were performed at the time of diagnosis. RV volumes, mass and function were assessed with CMR. RV contractility, afterload, RV-pulmonary artery (RV-PA) coupling and diastolic stiffness (Eed) were obtained using single beat pressure-volume loop analysis. Differences in RV phenotypes between iPAH and CTEPH were analyzed using multiple linear regression with interaction testing after correcting for confounders.

Results:
A total of 235 patients were included, 116 with CTEPH and 119 with iPAH. CTEPH patients were older, predominantly male, had a higher systemic blood pressure and a lower pulmonary vascular resistance at the time of diagnosis. After correcting for these confounders, RV function and RV-PA coupling were similar in both groups. However, CTEPH patients had a higher RV end-diastolic volume index (87±27 ml/m2 vs. 82±25 ml/m2), and a lower RV wall thickness (0,6±0,1 g/ml vs. 0,7±0,2 g/ml; figure 1A). The increase in afterload in CTEPH was associated with a disproportionally larger increase in diastolic stiffness compared to iPAH, independent of RV wall thickness (figure 1B).

Conclusions:
Despite a similar RV function, the RV in CTEPH is more dilated and stiffer than the RV in iPAH, independent of age, sex and afterload.
Abstract 14223: Identifying Pro-fibrotic Long Non-coding RNAs Ii Fibroblasts From the Failing and Non-failing Human Sinoatrial Node
Authors: Kalyanasundaram Anuradha , LI Ning , Hansen Brian , Gardner Miranda , Helfrich Katelynn M , Artiga Esthela , Janssen Paul M , Mohler Peter J , Mokadam Nahush , Whitson Bryan , Pietrzak Maciej , Freitas Mike , Fedorov Vadim V
Published: May 2021

Introduction:
Dense fibrous connective tissue is inherently found in the human sinoatrial node (hSAN), which further increases in heart failure (HF) leading to sinoatrial node dysfunction (SND). While several factors contribute to cardiac fibrosis, it is unknown if long non-coding RNAs (lncRNA), a novel class of RNA known to affect cardiac fibrosis, are involved in increasing fibrotic content in hSAN in non-failing (nHF) vs HF hearts.

Objective:
To identify unique lncRNA profiles and pro-fibrotic lncRNAs in isolated SAN and right atrial (RA) fibroblasts (FBs), in HF vs nHF human hearts.

Methods:
FBs isolated from pure SAN and RA tissues, from HF (n=6; 35-68yo) and nHF (n=4; 26-64yo) cardioplegically arrested human hearts, were cultured with/without transforming growth factor β1 (TGFβ1; 5ng; 48hrs) to activate myofibroblast (myoFB) transition. Frozen FBs and myoFBs were subjected to high throughput Next Generation RNA Sequencing analyses of the whole transcriptome.

Results:
Averages of total counts across all samples revealed that majority of the genes detected were protein coding 14415(63%), 5876 (26%) lncRNA, 1254 (5%) miscellaneous RNA, 677(3%) miRNA and 577 (3%) other types of RNA (Figure A). Preliminary analyses show that coding mRNA and non-coding lncRNA are differentially expressed in nHF hSAN and RA fibroblasts and TGFβ1 treated myoFBs. Furthermore, these expression patterns were also different in FBs and myoFBs isolated from failing hearts.

Conclusions:
Our findings show for the first time that lncRNA expression in cultured hSAN Fbs and myoFBs are unique and differentially altered in HF. Ongoing analyses of sequenced transcriptome will identify FB and myoFB lncRNAs associated with intrinsic higher levels of hSAN fibrotic content as well as in HF. We will also determine if they can modify pro-fibrotic activity in HF SAN FBs and myoFBs, which may be beneficial to develop novel molecular approaches to decrease HF-associated SAN fibrosis and associated SND.
Abstract 14227: Timing Since Last Hospitalization for Heart Failure and Risks of Cardiovascular Death and Hospitalization of Heart Failure
Authors: Norhammar Anna , Bodegard Johan , Thuresson Marcus , Eriksson Jan W
Published: May 2021

Introduction:
Hospitalization for heart failure (hHF) is a serious event where approximately 10% die in hospital, 30-40% are readmitted within 1-year and with very poor 5-year survival rates. However, little is known about CV death or hHF risks immediately one year post discharge in a modern real-world clinical setting with access to modern HF-therapies.

Hypothesis:
To examine the risks of CV death and hHF in relation to timing since last hHF prior to follow-up in a prevalent HF population.

Methods:
Linked hospital-, prescribed drug- and cause of death registry data from Sweden was used, and hHF patients were identified by main diagnosis at an in-hospital admission. Index date was 1
st
June 2018 and patients were grouped according to timing of hHF prior to index; <4, 4-8, 8-26, 26-52 and >52 weeks. Event rates were calculated per 100 patient years. Cox regressions adjusted for age, sex, ischemic heart disease, diabetes and chronic kidney disease were used to estimate risks.

Results:
Of 62,809 patients with a hHF; 2226 (4%), 1832 (3%), 5131 (8%), 6890 (11%) and 49,730 (74%) patients were allocated to the <4, 4-8, 8-26, 26-52 and >52 weeks groups respectively. The patient groups were similar, age 78 years, 44% women, 35% myocardial infarction but differences in CKD. Patients with the most recent hHF, <4 weeks, had the highest hHF or CV death and hHF event rates compared to the other groups, 105 and 84 events per 100 patient years, respectively. Compared with patients with the least recent hHF (>52 weeks), the risks of hHF or CV death and hHF were the highest in the group with the most recent hHF (<4 weeks); HR 5.46 (95% CI 5.07-5.89) and 7.22 (95% CI 6.60-7.89).

Conclusions:
In this large hHF cohort, patients with the most recent hHF timing prior to follow-up had by far the highest risks of hHF or CV death and hHF compared to patients with less recent hHF timing. This supports an urgent and prompt need for effective treatment early after hospitalization for HF, with limited acceptance for treatment inertia.
Abstract 14230: Integration of Vascular Phenotyping With Metabolomic Profiling in Black Subjects With Heart Failure With Reduced Ejection Fraction
Authors: Morris Alanna A , Nayak Aditi , Liu Chang , Jin Qingchun , Ko Yi-An , Udeshi Eisha , uppal karan , Liu Ken , Butler Javed , Jones Dean , Quyyumi Arshed A
Published: May 2021

Introduction:
Impaired vascular function in blacks contributes to a higher risk of heart failure (HF) compared to other race/ethnicities.

Hypothesis:
Black patients with HF with reduced ejection fraction (HFrEF) will have worse digital microvascular function measured using peripheral arterial tonometry (PAT). High resolution metabolomics profiling will identify novel biomarkers of vascular function.

Methods:
PAT was used to estimate the reactive hyperemia index (RHI) in blacks and whites with HFrEF (N=154, age: 53.7 ± 13.0 yrs, 48.7% female, 61.0% black) and healthy controls (N=200, age: 43.2 ± 14.0 yrs, 47.0% female, 27.0% black). Linear regression was used to determine if race was associated with RHI after adjustment for traditional CV risk factors. High-resolution plasma metabolomics profiling and pathway analysis, followed by metabolite confirmation with mass spectrometry were used to derive a metabolomics score (MS) from metabolites that were significantly associated with RHI, different between blacks and whites, and attenuated the association of black race with RHI.

Results:
Black subjects were younger in both the HFrEF and control cohorts. Blacks with HFrEF were more likely to have nonischemic HF and hypertension, more likely to be on hydralazine-nitrates and diuretics. RHI was lower in blacks than whites both in subjects with HFrEF (1.8 ± 0.5 vs. 2.0 ± 0.5, P=0.02) and in healthy controls (2.1 ± 0.5 vs. 2.4 ± 0.5, P=0.003). Black race was independently associated with lower RHI (adjusted β=-0.221, P=0.03). MS comprising metabolites representative of cardiac cachexia (3-Methyl-Histidine, L-Histidine, Creatinine), vascular collagen turnover (4-hydroxyproline), purine metabolism and oxidative stress (uric acid) attenuated the association of black race with RHI by 49.8%.

Conclusion:
Integration of vascular phenotyping with metabolomic profiling reveals a novel MS that attenuates the association of black race with impaired microvascular function.
Abstract 14244: Circulating Vascular Cell Adhesion Molecule-1 and Incident Heart Failure: The Multi- Ethnic Study of Atherosclerosis
Authors: Patel Ravi B , Colangelo Laura A , Bielinski Suzette J , Larson Nicholas B , Ding Jingzhong , Allen Norrina B , Michos Erin D , Shah Sanjiv J , Lloyd-jones Donald M
Published: May 2021

Background:
Serum levels of vascular cell adhesion molecule-1 (VCAM-1) are reflective of endothelial activation, a pathologic process that is associated with subclinical cardiac dysfunction. While VCAM-1 has been implicated in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFpEF), the prospective association of VCAM-1 with clinically overt HF is unclear.

Methods:
In the Multi-Ethnic Study of Atherosclerosis, we evaluated the association of VCAM-1 at Exam 2 (2002-2004) with incident HF across ejection fraction (EF) categories (HFpEF and HF with reduced EF [HFrEF]) after adjustment for cardiovascular risk factors. Incident HF was adjudicated as first hospitalization for symptomatic HF, requiring specific clinical and/or imaging criteria.

Results:
Of 2,298 participants (mean age: 63.0 years, female: 53%), those with higher VCAM-1 were more likely white race, had higher blood pressure, and lower renal function. Over a median of 16.0 years, there were 102 HF events (HFpEF = 65; HFrEF = 37) (
Figure
). After covariate adjustment, VCAM-1 was independently associated with incident HF (
Table
). Upon evaluation of HF subtypes, VCAM-1 was associated with incident HFpEF, and risk effect estimates were consistent for incident HFrEF. The association of VCAM-1 with incident HF was consistent across the spectrum of age, sex, and BMI.

Conclusion:
In a multiethnic cohort, VCAM-1 was independently associated with incident HF over long-term follow up. These findings suggest a potential role for endothelial activation in driving clinical HF. Lifestyle and pharmacologic therapies that decrease endothelial activation may prevent the progression to clinical HF.
Abstract 14251: Creation and Validation of a Novel Sex-specific Mortality Risk Score in LVAD Patients
Authors: Nayak Aditi , Hu Yingtian , Ko Yi-An , Steinberg Rebecca , Das Subrat , Mehta Anurag , Liu Chang , Pennington John , Xie Rongbing , Kirklin James K , Kormos Robert L , Cowger Jennifer , Simon Marc A , Morris Alanna A
Published: May 2021

Introduction:
Prior studies have shown that females have worse 3-month survival post-LVAD. Currently used prognostic scores including the Heartmate II Risk Score (HMRS), were developed in >75% male cohorts, and may not account for the increased residual risk in females.

Hypothesis:
A sex-specific risk score will predict post-LVAD mortality in females, and perform better than HMRS.

Methods:
Adult CF-LVAD patients from the ISHLT Mechanically Assisted Circulatory Support (IMACS) registry (Implant years: Jan 2013 - Sep 2017, age: 56 ± 13 yrs, 21% female, 36% centrifugal pumps) were randomly divided into derivation (DC, n=9113, 21% female) and validation cohorts (VC, n=6074, 21% female). Primary outcome of interest was 3-month mortality. IMACS risk score (IMACS-RS) was developed in the DC, from pre-operative candidate predictors selected using Akaike Information Criterion, or significant sex*variable interaction.

Results:
There were 1,466 deaths (9.7%) within 3 months after implant. In the DC, age, cardiogenic shock at implant, Body Mass Index, Blood Urea Nitrogen, bilirubin, hemoglobin, albumin, platelet count, LV End Diastolic Diameter, Tricuspid Regurgitation, dialysis and major infection pre-implant were retained as significant predictors of 3-month mortality. There was a significant ischemic HF*sex and platelet count*sex interaction. For each quartile increase in IMACS-RS, females had 93% increased odds (p<0.0001), and males had 86% increased odds (p<0.0001) of 3-month mortality. IMACS-RS represented a significant improvement over HMRS (p<0.01 for improvement in AUC) and provided excellent risk calibration in both sexes (no significant difference between observed and predicted risk). Removal of sex-specific interaction terms resulted in significant loss of model fit.

Conclusions:
A sex-specific risk score provides excellent risk prediction in LVAD patients. Future prognostic studies in advanced HF should present sex-specific secondary outcomes.
Abstract 14259: Eosinophilic Granulomatosis Presenting as Non-ST Segment Elevation Myocardial Infarction
Authors: Gaurav Karsh , Shenoy Vinayak , Fisher Perry , Steinberg Jordan , Anderson Todd , Bhandary Akshai
Published: May 2021

Background:
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis characterized by small to medium size vessel vasculitis. Here, we present a case of newly diagnosed EGPA presenting as non-ST segment elevation myocardial infarction (NSTEMI).

Case:
A 53-year-old male with a history of asthma and nasal polyps presented with acute onset anginal chest pain, rising troponin T and CKMB without ischemic changes on electrocardiogram. He was admitted for NSTEMI. Cardiac catheterization showed non-obstructive coronary artery disease (Figure 1). Given his past medical history along with eosinophilia and pulmonary opacities seen on CT chest, there was concern for EGPA. Lung wedge resection biopsy showed parenchymal eosinophilia, granulomatous inflammation, and vasculitis that confirmed the diagnosis (Figure 2). Figure 1 Figure 2

Discussion:
Cardiac involvement is known to be a major contributor to disease-related death, totaling up to 50% of cases, and therefore poses an important aspect of this rare disease. Recent reports, particularly concerning clinical differences given ANCA status, have shown that these patients might represent a heterogeneous group. For instance, ANCA-negative patients, such as our patient, more frequently develop heart conditions. We cultivate such discussion not only to bring attention to EGPA as an uncommon entity to the practice of many cardiologists, but also to point out that early recognition of cardiac involvement could reduce morbidity and mortality.
Abstract 14260: Transcatheter Aortic Valve (tavr) Outcomes Among Hospitalizations for Coronary Artery Disease: An Insight From National Inpatient Sample 2016
Authors: Voruganti Dinesh C , Hassan Hafeez , Dugyala Sushma , Amanullah Aman M
Published: May 2021

Background:
Trans-catheter Aortic Valve Replacement (TAVR) is an increasingly sought option for aortic stenosis over the open-surgical treatment. Ongoing studies continue to investigate the outcomes of TAVR. However, the outcomes among Coronary Artery Disease (CAD) remain less explored.

Aim:
Evaluate the hospitalization outcomes for patients with TAVR with and without CAD.

Methods:
The National Inpatient Sample (NIS) 2016 was used to evaluate the outcomes among hospitalizations related to TAVR. Adult hospitalizations (age >= 18) for TAVR was identified using the ICD 10 procedure code 02RF3. CAD was identified using the ICD 10 codes I25.10, I2511, I25110, I25111, I25118, I25119, I252, I255, and I256. Demographics, In-hospital mortality, Length of stay were abstracted using the variables mentioned in the database. The presence of cardiac tamponade, stroke, acute kidney injury, arrhythmias (AV block, Afib) was identified using Dx codes (ICD 10). All analysis was performed using SAS 9.4 software.

Results:
During the year 2016, there were a total of 40,000 TAVR related hospitalizations. CAD was present among 28200 hospitalizations. The mean age among both groups was almost identical to ~ 80 years. Among CAD, there were 39.91% females and among non-CAD females constituted 59.8%. No significant differences were noted for Length of stay among both groups (t-test P =0.0588). In-hospital mortality was higher among non-CAD group (2.84% vs. 1.43%, P <0.0001). The prevalence of third-degree AV block was similar in both groups (9.65% vs. 9.66%, P=0.9615). Cardiac tamponade was higher among the non-CAD group (1.61% vs. 0.76%, P>0.0001). Acute kidney injury was slightly higher in the CAD group (12.32% vs. 11.65%, P=0.0611). Atrial fibrillation was higher among the CAD group (18.33% vs. 16.95%, P=0.0010). Stroke was significantly higher among non-CAD group (0.13% vs. 0.04%, P =0.0008)

Conclusion:
CAD is present in about 70% of TAVR hospitalizations. Fewer females were present in the CAD group. Higher in-hospital mortality, stroke, and cardiac tamponade were noted in the non-CAD group, while AKI and AF were higher in the CAD group. Higher prevalence of death, stroke, and tamponade in the non-CAD group need further study.
Abstract 14267: Evinacumab Lowers LDL-C in Patients With Homozygous Familial Hypercholesterolemia Irrespective of Background Lipid-lowering Medication
Authors: Raal Frederick J , Rosenson Robert S , Reeskamp Laurens F , Hovingh G. Kees , Kastelein John J , Rubba Paolo , Ali Shazia , Banerjee Poulabi , Chan Kuo-Chen , Khilla Nagwa , McGinniss Jennifer , Pordy Robert , Zhang Yi , Gaudet Daniel
Published: May 2021

Background:
Homozygous familial hypercholesterolemia (HoFH) is characterized by very premature atherosclerotic cardiovascular disease due to profoundly elevated levels of LDL-C. Attempts to lower LDL-C in patients with HoFH often require multiple lipid-lowering medications (LLMs). Evinacumab, an angiopoietin-like protein 3 inhibitor, has been shown to reduce LDL-C in patients with HoFH by approximately 50% when added to maximally tolerated background LLMs.

Objective:
In this post-hoc analysis we assessed efficacy of evinacumab in patients with HoFH according to background LLM type.

Methods:
This was a double-blind, placebo-controlled, 24-week phase 3 trial (NCT03399786) that randomized patients 2:1 to receive intravenous (IV) evinacumab 15 mg/kg (n=43) or IV placebo (n=22) every 4 weeks. The effect of background LLMs on the efficacy of evinacumab to lower LDL-C was assessed for the following subgroups: high intensity-statin, low-intensity statins, lomitapide, triple therapy (ezetimibe + PCSK9 inhibitor + statin), and quadruple therapy (triple therapy + lomitapide). Primary endpoint was % LDL-C reduction from baseline to week 24.

Results:
At baseline, 55.4% (evinacumab, 58.1%; placebo, 50.0%) of HoFH patients were on triple therapy. Overall, 93.8% were on statins (76.9% on high intensity statins). Across LLM subgroups, mean baseline LDL-C levels ranged from 166.8 mg/dL to 281.8 mg/dL (Table). From baseline to week 24, marked reductions in LDL-C occurred with evinacumab treatment, which were observed in all groups: quadruple therapy (66.8%), triple therapy (56.0%), lomitapide (49.6%), high-intensity statins (48.6%) and low-intensity statins (41.0%). Evinacumab was generally well-tolerated.

Conclusions:
Evinacumab substantially lowers LDL-C levels in patients with HoFH irrespective of background LLM.
Abstract 14276: A Pediatric Cardiology Handbook for the Digital Age
Authors: Rochelson Ellis , Clark Bradley C , Motonaga Kara
Published: May 2021

Background:
Pediatric cardiology (PC) fellows, tasked with studying a large and dynamic field, may benefit from a quick-access digital resource that reflects contemporary practice.

Objective:
To design a PC Handbook smartphone app and evaluate its effectiveness in enhancing the accessibility of information such as guidelines and treatment recommendations for PC fellows.

Methods:
The PC handbook app was designed for iPhone using XCode and Swift programming. A pre-app electronic survey and instructions for download were sent to U.S. PC fellows followed by a post-app survey within 3 months of use. Fellows were asked to rate the ease of rapid access to various types of information, such as guidelines and normal values, with responses given on a 4-point scale (1 = very difficult, 4 = very easy). Responses were compared pre- and post-app using the Wilcoxon signed-rank test.

Results:
Two-hundred and thirty PC fellows were contacted; 23% (total n = 53) completed both the pre-app and post-app surveys and were included for analysis. Over half (57%) of fellows used the PC handbook app 1-3 times per month while 17% used it at least 1-3 times per week. After using the app, fellows found it easier to quickly access information in 8 out of 9 domains evaluated (Fig 1). All fellows found the app easy to use (100%), most felt that the app is well-organized (98%), contains reliable information (92%), and is useful for finding quick answers to clinical questions (87%). Almost all (91%) would recommend the app to a colleague.

Conclusions:
The Peds Cardiology Handbook iPhone app is a useful, reliable tool that provides quick access to high yield information, including various guidelines and references, in one location. Overall, PC fellows found it easier to rapidly access clinically relevant information after using the app, though future studies may be necessary to evaluate long-term use and impact on evidenced-based practice.
Abstract 14277: Serum Nt-prob-type Natriuretic Peptide is Associated With Coronary Microvascular Dysfunction in Patients With Angina and Non-obstructive Coronary Artery Disease
Authors: Ahmad Ali , Sara Jaskanwal D , Corban Michel T , Toya Takumi , Ozcan Ilke , Lerman Lilach O , LERMAN Amir
Published: May 2021

Title:
Serum NT-proB-type Natriuretic Peptide is associated with Coronary Microvascular Dysfunction in Patients with Angina and Non-obstructive Coronary Artery Disease

Authors:
Ali Ahmad, MD, Jaskanwal D. Sara, MBChB, Michel T. Corban, MD, Takumi Toya, MD, Ilke Özcan, MD, Lilach O. Lerman, MD PhD, Amir Lerman, MD

Introduction:
Coronary microvascular dysfunction (CMD) is prevalent in patients with heart failure with preserved ejection fraction. Subclinical ischemia and myocardial fibrosis in CMD might raise filling pressure, a hallmark of HFpEF, which induces secretion of NT-proB-type natriuretic peptide (NTpro-BNP). We sought to explore the relationship between CMD and NT-proBNP.

Methods:
We studied 698 patients with signs and/or symptoms of ischemia and with non-obstructive CAD (<40% angiographic stenosis) who underwent invasive CMD evaluation and had NT-proBNP checked within 6 weeks. CMD was defined as coronary flow reserve (CFR) (hyperemic flow/baseline flow as measured by the doppler wire) of ≤2.5 in response to intracoronary adenosine injection.

Results:
Overall mean age was 52.8±12.2 years, and women represented 69% of the patients. Log NT-proBNP showed a modest inverse correlation with CFR (Pearson’s R = -0.22, P<0.0001;
Figure 1
), which remained significant after adjusting for age and gender (Standardized ß coefficient = -0.14; P = 0.001). Patients with CMD had higher levels of NT-proBNP than those without (82 [44-190] vs. 62 (33-130], P <0.0001;
Figure 2)
.

Conclusion:
Declining coronary microvascular function is correlated with higher NT-proBNP levels. Patients with CMD had higher levels of NT-proBNP, a marker of elevated LV pressure, contributing to the possible role of CMD in early HFpEF pathophysiology.

Keywords:
Coronary microvascular dysfunction, NT-proBNP
Abstract 14282: Association Between Hospitalization Costs and Left Ventricular Ejection Fraction in Patients With Heart Failure in the Advanced Aging Society
Authors: Ryota Kaichi , marume kyohhei , nakai michikazu , Ogata Soshiro , Ishii Masanobu , Mori Takayuki , Komaki Soichi , Toida Reiko , Kurogi Kazumasa , Miyamoto Yoshihiro , Yamamoto Nobuyasu
Published: May 2021

Introduction:
The economic burden associated with heart failure (HF) is expected to increase in the world due to aging. Left ventricular ejection fraction (LVEF) is a basic clinical index that indicates the severity of HF, and guideline-directed medical therapies are recommended stratified by LVEF. However, there is paucity of information between LVEF and hospitalization costs.

Hypothesis:
Therefore, we evaluated the association between the hospitalization costs and LVEF in elder HF patients in Japan, which is at forefront of aging.

Methods:
We studied 346 consecutive patients who admitted to Miyazaki prefectural Nobeoka Hospital due to HF between January 2015 and March 2018.

Results:
Median hospitalization costs were comparable between the HF reduced EF (HFrEF; LVEF<40%: n=129) and HF preserved EF (HFpEF; LVEF≥40%: n=217) ($7128 vs $6580,
P
=0.373), LVEF was not correlated with hospitalization costs (
P
=0.051) (Figure A). Meanwhile, in the subgroup aged over 75 years, median hospitalization costs were significantly higher in HFrEF than in HFpEF ($7249 vs $6471,
P
=0.031). The HFrEF group also had higher level of brain natriuretic peptide (1011 vs 479 pg/ml,
P
<0.001), higher prevalence of ischemic heart disease (40% vs 27%,
P
=0.004), and higher rate of percutaneous coronary intervention (10% vs 2%,
P
=0.008) than HFpEF group. In addition, LVEF was significantly correlated with hospitalization costs (
P
=0.005) (Figure B), and remained as a significant independent predictor of hospitalization costs in multivariate liner regression analysis (β=—0.173,
P
=0.014).

Conclusions:
LVEF was not significantly correlated with hospitalization costs in the entire cohort, but was an independent negative factor for hospitalization costs in the subgroup of aged over 75. This might provide helpful evidence for future novel healthcare strategies that target HF inpatient cost reductions.
Abstract 14285: Scoring Tool to Accurately Predict 10 Year Major Adverse Cardiac Events Following Drug-eluding Stent Placement
Authors: Ellis Stephen G , Huded Chetan , Lincoff A Michael , nair ravi , Kapadia Samir R
Published: May 2021

Background:
Although most drug-eluding stent (DES) patients live longer than 10 years, there is no generally accepted clinical tool to predict risk of major adverse cardiac events (MACE) after DES over that period of time.

Methods:
Local consecutive patients receiving their first limus-eluting DES from 6/04-6/12 were characterized at baseline and prospectively followed. Patients were randomly allocated to a training or validation cohort, and a predictive Cox model using pre-procedural variables was developed in the training set. This model was then retested in a validation cohort. The primary endpoint was the c-index in the validation cohort. CIF and Fine-Gray were used for sensitivity analysis.

Results:
Patients (n=1321) had mean follow up of 10±3 years (3% were lost to follow up). Baseline characteristics included age=63±11 years, 65% male, SYNTAX Score=10±7, 1st/2nd Gen DES (%)=42.8/57.2, DES length (mm)=33±22.

In the training set, MACE was independently correlated with renal insufficiency (p<0.001), prior CABG (p=0.003), LVEF (p=0.004), restenotic lesion (p=0.013), insulin use (p=0.023), peripheral vascular disease (PVD) (p=0.030), age (p=0.037) and SYNTAX score (p=0.047). Assigning 1 point each to these 8 parameters (and dichotomizing continuous variables at age≥75, LVEF≤35 and SYNTAX score ≥23) resulted in 10 year Kaplan-Meier MACE in the validation set of 0=35.2%, 1=53.0%, 2=79.0%, ≥3=100.0% (figure), c-index= 0.81. Within the low risk group, if complete revascularization could be achieved the risk dropped to 28.2%.

Conclusions:
Ten year risk of MACE can be accurately modeled using this simple model, with risk ranging from about 30% to nearly 100%.
Abstract 14286: Significance of Nutritional Status in Patients With Chronic Limb Threatening Ischemia
Authors: Ikeoka Kuniyasu , Kimura Stephen , Dash Siddhartha , Hammad Tarek , Li Jun , Shishehbor Mehdi
Published: May 2021

Introduction:
The nutrition status plays a key role in the pathogenesis of frailty, and is strongly associated with the prognosis of patients with chronic limb-threatening ischemia (CLTI). The Geriatric Nutritional Risk Index (GNRI) is a widely used, simple, and well established nutritional status screening method. The association between the GNRI and wound healing in patients with CLTI has not been established.

Hypothesis:
We assessed the hypothesis that GNRI is associated with wound healing in patients with CLTI.

Methods:
We conducted a single-center retrospective analysis for 172 consecutive CLTI patients who were admitted to our hospital from August 2017 to April 2019 (age 70±14 years; men 62.2%). The GNRI on admission was calculated as follows: [14.89 х albumin (g/dL)] + [41.7 х (bodyweight/ideal body weight)]. According to the GNRI values, 4 grades of nutrition-related risk are defined as major risk (GNRI:<82), moderate risk (GNRI: 82 to <92), low risk (GNRI: 92 to 98), and no risk (GNRI: >98). The amputation-free survival (AFS) and the cumulative wound healing rate are calculated by the log-rank test. The receiver operating characteristic curve was used to obtain a cutoff value for wound heal. Cox proportional hazards regression analysis was performed to explore the independent association between the GNRI and wound heal.

Results:
The follow-up period was 12±6.7 months. The 1-year AFS in no risk, low risk, moderate risk, and major risk groups were 90%, 74%, 66%, and 62%, respectively (
P
=0.045). GNRI was significantly associated with WIfI wound score (W1, 95±8.8; W2, 87±8.0; W3, 84±9.3,
P
<0.001). The 1-year cumulative wound healing rate in no risk, low risk, moderate risk, and major risk groups were 56%, 45%, 37%, and 32%, respectively (
P
=0.036). GNRI=95 was selected as cutoff value with maximum discriminative power for wound healing (sensitivity 70%, specificity 60%; Area under the curve, 0.67; 95% confidence interval, 0.59-0.76). GNRI>95 was an independent predictor of wound healing (Hazard ratio, 1.9; 95% confidence interval, 1.0-3.7;
P
=0.046).

Conclusions:
The GNRI was significantly associated with AFS and wound healing in patients with CLTI. GNRI=95 is a novel cutoff value to predict wound healing during follow-up.
Abstract 14300: The Relationship Between the American Heart Association’s Life Simple 7, Ectopic Fat and Insulin Resistance Among South Asians: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study
Authors: Chevli Parag A , Mongraw-chaffin Morgana , Mehta Anurag , Ahmad Muhammad Imtiaz , Kanaya Alka M , Blaha Michael J , Blankstein Ron , Nasir Khurram , Talegawkar Sameera , Xu Jiaqian , Shapiro Michael D
Published: May 2021

Introduction:
The inverse association between ideal cardiovascular health (CVH) as measured by AHA’s Life simple 7, and cardiovascular disease (CVD) incidence is well documented. However, research exploring the association between CVH and surrogate markers of cardiometabolic disease, including ectopic fat depots, insulin resistance, and β-cell dysfunction is sparse.

Methods:
Among 906 South Asian participants (mean age 55 y, SD=9.4, 46% women) in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort, we assigned each LS7 component a score of 0, 1, and 2, and summed these scores to derive an overall CVH score. Visceral, subcutaneous, pericardial, and intermuscular fat and hepatic fat attenuation were measured using computed tomography. We used a homeostasis model assessment for insulin resistance (HOMA-IR) for insulin resistance and HOMA-β for β-cell function. We used multiple linear regression to model the associations between CVH score and natural log-transformed ectopic fat measures, HOMA-IR, and HOMA-β.

Results:
In adjusted analysis, compared to those with ideal CVH, participants with poor CVH demonstrated 53.9% (95% CI, 39.7 - 69.4) higher visceral fat area, 66.5% (50.5 - 84.2) higher pericardial fat volume, and 35.1% (23.0 - 48.4) higher subcutaneous fat area, but only 8% (3.1 - 13.0) higher intermuscular fat area and 15.9% (11.2 - 20.4) higher intrahepatic fat (all p<0.001). Also, poor CVH was associated with 154% (117.5 - 198) higher HOMA-IR. Similarly, participants with intermediate CVH demonstrated significantly larger measures of ectopic fat and HOMA-IR. There was no significant association between CVH and HOMA-β.

Conclusion:
We found that poor and intermediate CVH, as defined by LS7 metrics, was associated with significantly higher measures of ectopic fat and insulin resistance among South Asians. Long-term follow-up of the MASALA cohort will examine the association of LS7 metrics with the incident CVD events.
Abstract 14301: Effects of Septal Reduction Therapy on Acute Cardiovascular Events and All-cause Mortality in Patients With Obstructive Hypertrophic Cardiomyopathy: Propensity Score-matched Study
Authors: Morita Sae , Zhao Yanling , Hasegawa Kohei , Reilly Muredach P , Maurer Mathew S , Takayama Hiroo , Shimada Yuichi J
Published: May 2021

Introduction:
Septal reduction therapy (SRT) - i.e., septal myectomy and alcohol septal ablation - has been used to treat medically-refractory obstructive hypertrophic cardiomyopathy (HOCM) for a few decades. However, the effects of SRT on the risk of acute cardiovascular (CV) events and all-cause mortality are largely unknown.

Hypothesis:
SRT is associated with a long-term decrease in acute CV events and a short-term increase in all-cause mortality in patients with HOCM.

Methods:
We performed a propensity score (PS)-matched study using all-payer databases that capture all hospitalizations and outpatient visits in New York State. We identified patients with HOCM who underwent SRT between January 1, 2007 and December 31, 2014 (i.e., the SRT group) and those who have never had SRT but had at least one hospitalization for HOCM during the same period (i.e., the control group). We performed 1:1 PS matching using age, sex, race/ethnicity, source of payment, season and year of starting event follow-up (i.e., the day of SRT or the index hospitalization), and Elixhauser comorbidity measures. The primary outcomes were (1) acute CV event (i.e., emergency department visit or unplanned hospitalization for CV disease) during 1-360 days and 361-720 days and (2) 7-, 15-, 30-, 180-, and 360-day all-cause mortality. We compared the risk of the outcome event using logistic regression models.

Results:
The analytic cohort consisted of 690 patients with HOCM (i.e., 345 PS-matched pairs). The SRT group had a lower risk of acute CV event during 361-720 days (OR 0.44; 95% CI, 0.20-0.97; P=0.04) but a higher risk of 7-day mortality (11 vs. 2 in the control group; P=0.03). The SRT group had a non-significant trend towards lower all-cause mortality in longer terms (
Figure
).

Conclusion:
In this population-based PS-matched study of patients with HOCM, SRT was associated with a reduced risk of acute CV events in the second post-procedure year at the sacrifice of a short-term increase in all-cause mortality.