bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10271: Correlates and Prognostic Significance of B-Type Natriuretic Peptide in Patients with Sickle Cell Hemoglobinopathies
Authors: Gupta Ashwin , Farber-Eger Eric , Gupta Deepak K
Published: March 2022

Introduction:
Natriuretic peptides (NP) are hormones released from the heart in response to cardiac stress. Sickle cell hemoglobinopathies are conditions with increased cardiovascular stress, yet few studies have examined determinants of and the relative prognostic significance of NP levels in these patients.

Hypothesis:
We assessed the hypothesis that plasma B-type NP (BNP) level is one of the strongest independent predictors of death among patients with sickle cell hemoglobinopathies.

Methods:
From the Vanderbilt University Medical Center electronic health record, we retrospectively studied adult patients with sickle cell disease (SCD, n = 278; median age 30 years, 50% female) and sickle trait (ST, n = 196; median age 45 years, 73% female) in whom BNP was clinically measured from 2003-2020. The association between BNP and risk of death was assessed with multivariable Cox regression. Correlates of BNP levels were examined in multivariable ordinal logistic regression.

Results:
Over 1846 person-years of follow-up, 43 (9%) patients died. BNP, age, and lactate dehydrogenase levels were the three strongest predictors of death, accounting for 29%, 18%, and 13% of the explained variance in the risk of death, respectively. Each 110 pg/ml greater BNP was associated with a 5% (95% CI: 4-6%) increased risk of death. SCD was associated with a 19% (95% CI: 5 to 36%) increased risk of death compared to ST. Among patients with SCD, significant correlates of BNP ranked by strength of association were hemoglobin, white blood cell count, age, pulmonary artery systolic pressure (PASP), hypertension, left ventricular ejection fraction (LVEF), and neutrophil count (Figure). For patients with ST, the strongest correlates of BNP were PASP, hemoglobin, stroke, age, diabetes, and LVEF.

Conclusions:
In conclusion, BNP is the strongest predictor of death independent of anemia severity and other features of cardiac structure and function among patients with sickle cell hemoglobinopathies.
Abstract 10279: Altered Myocardial Gene Expression in
H2-kbm1
Mice with Orexinergic Dysfunction and Heart Failure
Authors: Stoller Douglas , Dhar Kajari , Basma Hesham , Bonasera Stephen J , Lowes Brian D
Published: March 2022

Introduction:
Mice carrying a homozygous frameshift mutation of the class I major histocompatibility antigen H2-K1 (H2-Kbm1) exhibit impaired development of hypothalamic orexinergic neurons. Similar to mice lacking the hypocretin (orexin) 2 receptor, H2-Kbm1 mice develop dilated cardiomyopathy and systolic heart failure (HF) from an early age. Previous studies suggest response to orexinergic signaling is predictive of patient response to current HF pharmacotherapeutic regimes. Our goal was to characterize the myocardial gene expression profiles of H2-Kbm1 mice.

Methods:
RNA was isolated from mice hearts (wild type n=5, mutant n=7) via the Qiagen RNeasy Mini Kit. DNase treatment was done to limit contamination of genomic DNA. Gene expression was measured using Illumina nexteq500 and 550 sequencing systems from a DNA library generated via the NuGene library kit (10 ng RNA). RNA-seq data analyses including comparisons, volcano and heatmap plots were completed.

Results:
H2-Kbm1 mice differentially express 398 myocardial genes compared to control mice. Ingenuity pathway analysis indicates that these genes are involved in necrosis of cardiac muscle (z-score -1.8), cell death (z-score 1.6), and cardiac contractility (z-score -4). Upstream signaling analysis suggest regulation by Mir-122 (z-score 2.4), DNMT3 A and B (z-score 3.3 and 2.5), VEGF (z-score 4.6) and rosiglitazone (z-score -6.8). Canonical pathway analysis is shown in Figure 1.

Conclusion:
H2-Kbm1 mice develop heart failure with marked myocardial transcriptional abnormalities that lead to impaired cardiac contraction and cell death. Differentially expressed genes are predominantly involved in mitochondrial function, oxidative phosphorylation, sirtuin signaling and the TCA cycle. Regulation of these genes is associated with miR-122, DNA methylations by DNMT3 A & B, VEGF and rosiglitazone signaling. The orexin pathway is a potential target for heart failure therapeutics.
Abstract 10280: The Association of Obesity Level and In-Hospital Survival of Patients with Covid-19 Who Received Corticosteroids
Authors: So Matsuo , Takahashi Mai , Egorova Natalia , Kuno Toshiki
Published: March 2022

Introduction:
Obesity is one of the most frequent comorbidities among COVID-19 patients. Although previous studies have shown higher body mass index (BMI) is associated with higher mortality, steroids as the current standard treatment for moderate to severe COVID-19 infection were not applied in most patients in these studies.

Hypothesis:
We hypothesized that patients with higher BMI still have higher mortality even on steroids.

Methods:
We conducted a retrospective study of 4,587 hospitalized patients with COVID-19 who received corticosteroids between March 1
st
, 2020, and March 30
th
, 2021. We divided patients into 6 groups by BMI[MOU1] (less 18.5, 18.5-25, 25-30, 30-35, 35-40, 40 or greater, kg/m
2
) and investigated in-hospital mortality as the primary outcome, in-hospital mortality among severe COVID-19 patients which was defined as requiring intensive care unit or endotracheal intubation as a subgroup analysis, and acute kidney injury (AKI) incidence rate as the secondary outcome.

Results:
Patients with higher BMI were younger and more likely to have a history of asthma, obstructive sleep apnea, diabetes, and less likely to have malignancies. The smooth spline curve showed J curve association of BMI with risk adjusted in-hospital mortality with flexion point at BMI between 25 and 30 kg/m
2
(Figure 1). Compared to overweight (25≤BMI<30 kg/m
2
) patients, class III obesity (BMI>40 kg/m
2
) was associated with higher risk adjusted in-hospital mortality overall (Table 1) as well as among patients with severe COVID-19 (OR [95% CI]: 3.21 [1.86-5.66], P<0.001). Class III obesity was also associated with a higher risk adjusted incidence of AKI (OR [95% CI]: 1.52 [1.06-2.18], P=0.024) compared to overweight patients.

Conclusions:
Class III obesity was associated with higher in-hospital mortality and AKI incidence rate in COVID-19 patients with steroids treatment.
Abstract 10289: Costs of Endoscopic vs Open Vein Harvesting for Coronary Artery Bypass Grafting: Insights from the Regroup Trial
Authors: Wagner Todd , Hattler Brack , Stock Eileen , Biswas Kousick , Bhatt Deepak , Bakaeen Faisal , Zenati Marco
Published: March 2022

Introduction:
Endoscopic Vein Harvesting (EVH) provides comparable rates in major adverse cardiac events to Open Vein Harvest (OVH) based on the intermediate-term results of the REGROUP Trial. Value based purchasing places more pressure to examine whether minimally invasive techniques, e.g., EVH, yield intended or unintended economic effects. The objective of this study was to compare health care costs between participants randomized to EVH or OVH during coronary artery bypass graft (CABG) surgery in the REGROUP trial.

Hypothesis:
We hypothesized that EVH would result in lower discharge and follow-up costs compared to the traditional OVH.

Methods:
Department of Veterans Affairs Cooperative Studies Program #588 (Clinicaltrials.gov NCT01850082) randomized 1150 participants (574 OVH, 576 EVH) at 16 VA medical centers. We linked participants to VA administrative data in VA’s Corporate Data Warehouse and extracted activity-based cost data starting with the index surgery. We analyzed discharge costs for the index surgery as well as follow-up costs in 30-day periods for EVH vs. OVH, comparing results from different statistical models to test for robustness. All costs were standardized to 2020 US dollars.

Results:
The unadjusted average cost for CABG patients with EVH and OVH was $76,607 (SD $43,883) and $75,368 (SD $45,900), respectively; the costs include both facility and provider costs. Despite the skewed variation in costs, there were no significant differences in discharge costs and high-cost patients were equally likely in both groups. We also found no significant differences in follow-up costs; the average follow-up period was 33 months (maximum follow-up was 85 months). The results were highly robust to the statistical model.

Conclusions:
Endoscopic harvesting was not associated with a reduction in costs for the index CABG surgery or follow-up care, nor was it associated with increased costs through unintended events. Therefore, the choice to provide endoscopic harvesting should be based on surgeon and patient preferences.
Abstract 10294: Endothelial Pannexin1-TRPV4 Signaling Regulates Pulmonary Arterial Pressure
Authors: Daneva Zdravka , Chen Yen Lin , Ottolini Matteo , Isakson Brant E , Sonkusare Swapnil K
Published: March 2022

The pulmonary endothelial cells (EC) dilate small pulmonary arteries (PAs) and maintain low pulmonary arterial pressure (PAP). Importantly, the loss of EC function contributes to elevated PAP in pulmonary hypertension (PH). Recent studies show that Pannexin 1 (Panx1), an ATP efflux pathway at the cell membrane, is a critical regulator of endothelial function. However, the impact of endothelial Panx1 (Panx1
EC
) on PA contractility and PAP is unknown. We observed that the extracellular ATP (eATP) levels are reduced in PAs from inducible, EC-specific Panx1
-/-
(Panx1
EC
-/-
) mice, identifying Panx1
EC
as an important ATP release pathway in PAs. Our recently published findings demonstrated that eATP dilates PAs via activation of Ca
2+
influx through endothelial transient receptor potential vanilloid 4 (TRPV4
EC
) ion channels. Therefore, we hypothesized that endothelial Panx1—eATP—TRPV4 channel signaling dilates PAs and lowers resting PAP. Apyrase (10 U/mL), an ATP hydrolyzing enzyme, reduced the activity of TRPV4
EC
sparklets (individual Ca
2+
influx signals through TRPV4
EC
channels) in PAs, implying a constitutive regulation of TRPV4
EC
channels by ATP. The activity of TRPV4
EC
sparklets was lower in PAs from Panx1
EC
-/-
mice than controls, identifying Panx1
EC
as a novel promoter of TRPV4
EC
channel activity. Pressure myography studies in PAs (~ 50 μm) from Panx1
EC
-/-
and TRPV4
EC
-/-
mice showed higher constriction to thromboxane A2 receptor agonist U46619 (1-300 nM) compared to PAs from controls. Finally, right ventricular systolic pressure was higher in Panx1
EC
-/-
and TRPV4
EC
-/-
mice compared to the respective controls. These data indicated that Panx1
EC
—eATP—TRPV4
EC
channel signaling lowers PA contractility and PAP. ATP is an endogenous activator of purinergic receptor signaling. Inhibition of P2Y1 and P2X receptors did not alter ATP activation of TRPV4
EC
sparklets in PAs. However, P2Y2 receptor inhibition and EC-specific P2Y2 receptor deletion abolished ATP activation of TRPV4
EC
sparklets. Together, these data identify a novel Panx1
EC
—eATP—P2Y2R
EC
signaling pathway that enhances TRPV4
EC
channel activity and lowers PAP. Individual elements of this pathway may provide novel therapeutic targets for treating pulmonary vascular disorders.
Abstract 10296: Outcomes of Transcatheter Mitral Valve Repair in Patients with Acute Kidney Injury-A US National Inpatient Sample Analysis
Authors: Zahid Salman , Baqi Abdul , Shafaqat Madeeha , Salman Fnu , Adil Abid Nawaz Khan , Ullah Waqas , UBAID AAMER , Abbas Sakina , Muhammadzai Hamza , Khan Muhammad Atif , Inayat Arslan , Tanveer Ud Din Mian , Khan Muhammmad , Khan Muhammad U
Published: March 2022

Introduction:
Data on outcomes of transcatheter mitral valve repair (TMVR) in patients with acute kidney injury (AKI) remains limited.

Hypothesis:
AKI is associated with worse outcomes in patients undergoing TMVR

Methods:
We utilized the United States National Inpatient Sample database from the year 2015 to 2018 to evaluate outcomes of TMVR in AKI.

Results:
A total of 21,505 weighted hospitalizations were included in the analysis. Of the patients who underwent TMVR 3350 (15.6%) developed acute kidney injury. The mean age of patients undergoing TMVR was higher for patients with AKI compared to patients who did not develop AKI was 77 and 76 years respectively. A logistic regression model adjusted for age, gender and baseline comorbidities was developed for predictors of AKI. On adjusted comparison liver disease (OR 2.4 95% CI, 2-2.9), peripheral vascular disease (1.35, 95% CI 1.2-1.53), congestive heart failure (2.76 95% CI, 2.34-3.26) and history of weight loss (1.92 95% CI 1.64-2.25) were significant predictors of AKI. In-hospital mortality was higher for patients with AKI versus no AKI (10.1% vs. 0.7%, p<0.01). Length of stay (13 vs 3 days) and cost of stay ($80787 vs. $ 44086) was significantly higher for patients with AKI versus those who did not develop AKI.

Conclusions:
AKI is associated with increased in hospital mortality and increased health care resource utilization in patients undergoing TMVR.
Abstract 10298: Improving the Ability to Assess and Detect Delirium in Postoperative Cardiac Surgery Patients
Authors: Ellis Myra F , Civale Rachel , Farrell Debra , Simon Jordan , Mangodt Linnea , Awuku Mavis , Corbitt Sophia , Thomas Tonda , Granger Bradi B
Published: March 2022

Introduction:
Delirium is common in cardiac intensive care units due to illness related stress, polypharmacy, interventions, excessive light and noise, disorientation and sleep disruption. Delirium assessment is poor due to limited nursing knowledge and the lack of integrated features in electronic health platforms (EHR) to support accurate assessment and documentation.

Hypothesis:
We hypothesized that education on use of the Confusion Assessment Method for the ICU (CAM-ICU) and enhanced features in the EHR would improve the ability to detect delirium in our CTICU.

Methods:
We conducted a QI intervention using a PDSA approach and pre-post evaluation design. In the
Planning
phase audited 100 randomly selected charts to determine baseline documentation of delirium. We conducted a survey of nurses’ knowledge of delirium and documentation criteria and identified a knowledge deficit. In the
Do
phase, a multi-stage educational initiative was used to address delirium awareness, knowledge, and CAM-ICU documentation competency. Enhancements in the EHR were made to enable accurate assessment, documentation and scoring using embedded logic. Post-intervention audits (n=100) were performed.

Results:
Survey respondents (n=64) averaged 31 years old (SD 1.4) and had 6 years nursing experience on average (median=3, range <1-40). Nurses believed patients with delirium had longer ICU LOS and worse outcomes and patients would benefit from screening. Most lacked training in delirium screening (88.1%, n=58). Baseline documentation of at least one assessment of delirium was 44% (n=44) and post-intervention was 100% (p<0.001). Accuracy of CAM-ICU assessments at baseline was challenging to determine due to a single field (YES/NO/UTA) in the EHR, however, positivity of pre-intervention assessments was 1% (n=1) and post- intervention at least 1 positive CAM score was recorded in 33% (n=33) of patients (p<0.001).

Conclusions:
Findings suggest that a multi-stage educational intervention paired with EHR integrated scoring logic improves awareness, knowledge and documentation accuracy for delirium in the ICU, which may improve patient safety and ICU outcomes. Better assessment and documentation may improve patient safety and ICU outcomes.
Abstract 10299: One Acute Exposure to E-Cigarette Smoke Using Various Heating Elements and Power Levels Induces Pulmonary Inflammation
Authors: Shi Jianru , Dai Wangde , Chavez Jesus N , Carreno Juan , Zhao Lifu , Kleinman Michael T , Arechavala Rebecca J , Hasen Irene , Ting Amanda , Bliss Bishop , Monterrosa Mena Jessica E , Kloner Robert A
Published: March 2022

Background:
A new form of lung injury was described in electronic cigarette users beginning July 2019 with patients presenting with respiratory distress. The condition is known as E-cigarette (eC) or vaping product use associated lung injury or EVALI and was thought to be related to Vit E oils used to dilute cannabis. Whether a single acute exposure of eC smoke can induce lung injury has not been reported. The purpose of this study was to determine if such an acute exposure with eC smoke heated with different heating elements and power levels induced inflammatory changes in the lungs and heart.

Methods:
Rats were exposed to pure air or received a single, 4-hour exposure to eC vapor (50% propylene glycol, 50% vegetable glycerin; tobacco flavoring, n=16 in each group). The devices used either a stainless steel (SS) or nichrome (NC) heating element randomized to a low or high atomization power (45 versus 70 Watts). Rats were euthanized within 48 hours of exposure and hematoxylin and eosin stained lung and cardiac histology sections were assessed. Inflammatory cells were counted from 12 random areas per section at 10 х magnification.

Results:
The lung alveoli appeared normal in the air group (Figure, panel A); the eC groups using the SS or NC heating element with high or low power showed accumulation of inflammatory cells (mainly macrophages) in bronchial lumen (B), near the pleura (C), and within the alveolar spaces (D). The numbers of inflammatory cells per field in the lung parenchyma were significantly greater in the rats exposed to eC using SS or NC heating element compared to the air control group (P < 0.05, One way ANOVA, Tukey multiple comparison test; panel E). Cardiac tissue appeared normal with no evidence of inflammation.

Conclusion:
One 4-hour exposure to eC vapor, in the absence of vitamin E oil or nicotine, significantly increased the number of inflammatory cells in the lung. Effects were seen after exposures to vapor generated using SS and NC heating elements at either high or low power.
Abstract 10302: A Case for Ending Rifampicin Use in Endocarditis
Authors: Sousa Jose P , Lourenco Carolina N , Teixeira Rogerio , Goncalves Lino M
Published: March 2022

Background:
Rifampicin has been employed in various endocarditis antibiotic regimens, particularly in prosthetic,
staphylococcus aureus
(SA) and culture-negative cases. However, this practice is not without controversy.

Purpose:
To perform a meta-analysis aimed at ascertaining the efficacy and safety of adjunctive rifampicin use in endocarditis.

Methods:
We systematically searched MEDLINE, Embase, Web of Science, Cochrane Library and Google Scholar, from inception to June 1st, 2021, for studies comparing rifampicin-containing antibiotic regimens with those comprising no rifamycin derivatives, in the setting of endocarditis. The primary endpoint was all-cause death, while relapse, bail-out valvular surgery, microbiological failure (lasting positivity of blood cultures) and hepatotoxicity (fivefold or higher increase in transaminase levels) were secondary outcomes. SA infections were investigated separately, with respect to the primary endpoint. Mantel-Haenszel odds ratios (ORs) were pooled using traditional meta-analytic techniques, under a random-effects model.

Results:
2 randomized, 1 non-randomized prospective and 6 retrospective studies, featuring 886 patients (of whom 322 allocated to rifampicin), were included. While 8 studies addressed staphylococcal endocarditis (with 3 of them dealing exclusively with SA infections), prosthetic and culture-negative cases were only focused on 1 study each. There were 96 deaths (from 7 studies), 32 relapses (from 6 studies), 35 bail-out valvular surgeries (from 4 studies), 14 microbiological failures (from 2 studies) and 32 hepatotoxicity cases (from 5 studies). Rifampicin use was associated with a tendency towards higher all-cause mortality (OR 1.63, 95% CI 0.85-3.12, P 0.14, i
2
12%), which held true for SA infections (OR 1.63, 95% CI 0.67-3.92, P 0.28, i
2
20%), and bail-out valve surgery (OR 2.03, 95% CI 0.65-6.34, P 0.22, i
2
5%). Relapse and microbiological failures rates were similar between groups (OR 1.25, 95% CI 0.59-2.65, P 0.56, i
2
0% and OR 1.3, 95% CI 0.24-6.90, P 0.76, i
2
41%, respectively). Hepatotoxicity odds were greater in the rifampicin arm (OR 3.24, 95% CI 1.35-7.77, P 0.008, i
2
0%).

Conclusion:
Currently available evidence does not support rifampicin use in endocarditis.
Abstract 10303: CRRL290: A Novel and Mechanism-Based Therapeutic Peptide Targeting the Crosstalk Between Angiotensin II and the Natriuretic Peptide System for Cardiorenal Disease
Authors: Ma Xiao , Iyer Seethalakshmi R , Reginauld Shawn , Pan Shuchong , Zheng Ye , Cannone Valentina , Sangaralingham Jeson , Burnett John C
Published: March 2022

Introduction:
Therapeutic strategies dual-targeting renin-angiotensin system (RAS) and natriuretic peptide system (NPS), such as Sacubitril/Valsartan, have been proven promising in treating cardiorenal disease (CRD). However, mechanisms behind the crosstalk between RAS and NPS remain to be fully elucidated. While angiotensin II (ANGII), the central RAS hormone, is thought to interact with NPS at multiple levels, whether and how it may influence the actions of particulate guanylyl cyclase A (pGC-A), the receptor activated by ANP and BNP to increase its second messenger cGMP, has not been investigated.

Hypothesis:
We hypothesize ANGII naturally suppresses pGC-A activity and inhibition of this ANGII mediated action can be a new strategy to combat CRD.

Methods:
Studies consist of biomarker analyses in plasma from healthy humans, drug infusions in normal rats, molecular characterization in human HEK293 cells, and in vitro assessment of CRRL290, an innovative dual-functional peptide designed to activate pGC-A and inhibit protein kinase C (PKC).

Results:
In 128 healthy humans, plasma cGMP was positively associated with ANP or BNP in low (≤ 4.5 pg/mL) but not those with high (> 4.5 pg/mL) ANGII levels. Infusion of ANP (300 pmol/kg/min) in normal rats increased plasma and urinary cGMP, however ANP mediated cGMP generation was reduced in the presence of ANGII. Interestingly, suppression effect of ANGII on pGC-A was only recapitulated in HEK293 cell overexpressing both pGC-A and AT1R, but not in HEK293 cell overexpressing pGC-A alone. We also found PKC, a known downstream target of AT1R, was a key mediator as the suppression effect of ANGII was largely ablated by Go6983, a pan PKC inhibitor. Accordingly, we designed and synthesized CRRL290. Notably, CRRL290 had superior potency in cGMP generation compared to the currently best-in-class ANP-analog, MANP, in HEK293 cells.

Conclusions:
We demonstrate that ANGII is a natural suppressor of pGC-A via AT1R and PKC signaling. We also report for the first time that CRRL290, a novel bioengineered peptide that activates pGC-A receptor while inhibiting PKC signaling, potently generates cGMP. Our study provides new insights into the RAS-NPS interaction, and highlights a novel and mechanism-based therapeutic avenue for treating CRD.
Abstract 10306: Right Heart Dysfunction in Adults with Coarctation of Aorta - Prevalence and Prognostic Implications
Authors: Goda Ahmed , Shaik Likhita , Katta Renuka Reddy , Devara Janaki , Iftikhar Momina , Egbe Alexander C , Connolly Heidi M
Published: March 2022

Introduction:
Chronic elevation of left heart filling pressure causes pulmonary vascular remodeling, pulmonary hypertension, and right heart dysfunction. Although diastolic dysfunction is relatively common in patients with coarctation of aorta (COA), there are limited data about the prevalence and prognostic implications of pulmonary hypertension and right heart dysfunction in this population. The purpose of the study was to assess right heart function and hemodynamics in patients with COA, and to determine the relationship between right heart indices and clinical outcomes.

Methods:
Right heart structure, function and hemodynamics were assessed with these indices: right atrial (RA) volume, RA pressure, RA reservoir strain, right ventricular (RV) global longitudinal strain, RV end-diastolic area, RV systolic pressure, and tricuspid regurgitation severity. These indices were used to generate a composite right heart hemodynamic score (RHHS), range 0-5. We then assessed the relationship between RHHS and primary outcome (death/transplant) and secondary outcomes (heart failure hospitalization and hepatorenal function).

Results:
Of 821 COA patients, RA dysfunction, RV dysfunction, and pulmonary hypertension were present in 16%, 14%, and 20% of patients respectively. RHHS was independently associated with primary and secondary outcomes (p<0.001). For every unit increase in RHHS, we observed 83% increase in death/transplant and 71% increase in heart failure hospitalization.

Conclusions:
The current study underscores an important point, which is that COA is not just a disease of the left heart but can result in right heart dysfunction, and that the onset of right heart dysfunction is associated with adverse outcomes.
Abstract 10311: Increasing Inpatient Palliative Care Referrals for Veterans with Heart Failure: A Quality Improvement Initiative
Authors: Gruen Jadry , Merchant Naseema , Gillespie-Heyman Sarah , Shamas Tracy , Adelman Samuel , Bauer Margaret , Ruskin Andrea , Gandhi Parul
Published: March 2022

Background:
Heart failure (HF) portends significant morbidity and mortality. Integrating palliative care (PC) with HF management may improve quality of life, communication, and preparedness planning. At the VA hospital in West Haven, CT, PC was utilized in 6.5% of patients admitted with HF from October 2019 to September 2020. We sought to increase the percentage of referrals to PC from 6.5% to 20% by May 2021.

Methods:
PC referral criteria were developed and used to screen all patients admitted to the medical service with HF between October 2020 and May 2021. Patient-centered education on the benefits of PC was delivered initially to medical teams caring for patients who met PC referral criteria and subsequently to all teams. Changes were tested using Plan-Do-Study-Act (PDSA) cycles. Results were analyzed using run charts.

Results:
Between November 2020 and May 2021, there were 109 HF admissions in patients who were not already followed by PC. Thirty-one (28%) received a new PC consult. The mean age was 83 ± 9.5 years, median B-type natriuretic peptide was 1202 pg/mL, and mean hospital length of stay was 8 ± 5 days. Kansas City Cardiomyopathy Questionnaire-12 was performed on 15 of the 31 patients with a mean score of 60 ± 22. After our intervention, a shift in the percentage of referrals was demonstrated with 6 consecutive data points above the fixed baseline median (Figure). During the index hospitalization, 5 patients died, 4 of whom had a PC consult.

Conclusion:
Through multiple PDSA cycles, referrals to PC for patients admitted with HF increased from 6.5% to 28%. Patient-centered education was an effective tool to teach medical teams about the benefits of PC. Furthermore, inpatient teams more consistently and independently considered PC for patients with HF, representing a cultural shift. This Quality Improvement model may serve as a paradigm to improve the care of HF patients.
Abstract 10313: Gender and Strain Background Affect Cardiopulmonary Function in
Col4a3
-/-
Alport Mice
Authors: Iansen Irion Camila , Williams Monique , Eisenberg Trevor , Seo Grace , Lambert Guerline , Takeuchi Lauro , Young Karen C , Hare Joshua M , Shehadeh Lina A
Published: March 2022

Background:
Alport syndrome (AS) is a hereditary form of chronic kidney inflammation that results in renal failure (RF). We previously reported that
Col4a3
-/-
129J mice, a model of AS and RF, exemplified multiple features of heart failure with preserved ejection fraction (HFpEF). This study investigates the effect of 3 different genetic backgrounds on cardiopulmonary function in
Col4a3
-/-
mice.

Methods:
Male and female Col4a3
-/-
(Alport) and WT mice from 129x1/SvJ, C57Bl/6 and BALBC strain were examined using echocardiography, whole body plethysmography (WBP) and pressure-volume (PV) loop analysis. Ttest was used for statistical analysis. Four groups per strain were used (n= 4-15/group).

Results:
Compared with their respective age-matched WT controls, male and female 8-week-old
Col4a3
-/-
129x1/SvJ mice demonstrated impaired systolic function (EF of 56 to 43.7%, p=.002 for females and 50.9 to 42% for males, p=.044; SV, CO, p<.05) and diastolic dysfunction (increased IVRT from 15.3 to 21.7ms, p=.0009 for females; 16.6 to 26.2ms, p<.0001 for males; increased MPI, P<.05). Additionally, PV loop analysis showed an increased EDPVR and end diastolic pressure, prolonged time constant of LV relaxation, and decreased CO and SV (p<0.05). For
Col4a3
-/-
BalbC and
Col4a3
-/-
C57Bl/6 strains, only females exhibited systolic (BalbC: EF% 51 to 45.66%, p=0.106 for females and 43.5 to 40.8% for males, p=.51; B6: EF% 51.3 to 40.8% p=.02 for females and 48.4 to 40.9%, p=.31 for males; SV, CO, p<.05) and diastolic dysfunction (IVRT from 16 to 24.1ms for BalbC and 18.20 to 25.63ms for B6, p<0.05). Male
Col4a3
-/-
BalbC had an increase in minimum and end-systolic pressures, and an increased pressure at dV/dt-max. Male
Col4a3
-/-
C57Bl/6 mice had an increased ESPVR slope (p<.05). All strains except BalbC males demonstrated alterations (p<.05) in pulmonary function including decreased ventilation rate (MV) and respiratory frequency, decreased peak expiratory flow, EF50, increased expiratory time, relaxation time, inspiratory time, and time of pause at end-of-expiration.

Conclusion:
Both male and female
Col4a3
-/-
129x1/SvJ mice demonstrated impaired cardiopulmonary viability. However,
Col4a3
-/-
mice on BalbC or C57Bl/6 strains had cardiopulmonary deficits only in females.
Abstract 10316: De-escalation of Guideline-Directed Medical Therapy in Ambulatory Heart Failure: Insights from the EPIC-HF Trial
Authors: Lipsey Jonathan E , Allen Larry A , Helmkamp Laura , Harger Geoffrey , Swat Stanley , Dow Tristan , Matlock Dan D , McIlvennan Colleen K
Published: March 2022

Background:
Despite proven benefits of guideline directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF), multiple studies have shown that rates of GDMT prescribing are suboptimal worldwide. The recently completed EPIC-HF trial demonstrated that a pre-clinic patient activation tool significantly increased GDMT intensification following a visit with a cardiology provider. However, whether GDMT intensification was sustained or associated with subsequent de-escalation was unknown.

Methods:
The EPIC-HF trial reported GDMT intensification at 1 month follow-up after the initial clinic visit. We analyzed GDMT prescription data from 1 to 6 month follow-up to examine the effect of an initial GDMT intensification by 1 month on subsequent rates of GDMT de-escalation from 1 to 6 months.

Results:
A total of 282 patients completed 6 month follow-up. From the study visit to 1 month follow-up, 39.7% (n=112) had an initial GDMT intensification. An initial intensification was not significantly associated with subsequent de-escalation of any GDMT medication from 1 to 6 month follow-up (24.1% de-escalated after no initial change vs 28.6% after initial intensification, p=0.40), nor was it significantly associated with de-escalation of any individual class of medication (BB 8.8% vs 11.6%, p=0.44; ACE-I 5.9% vs 8.9%, p=0.33; ARB 5.3% vs 6.3% p=0.73; MRA 6.5% vs 8.0%, p=0.62). Initial GDMT intensification was associated with dose reduction or discontinuation of loop diuretic (4.1% vs. 11.6%, p=0.02).

Conclusions:
Patients who had GDMT intensified at an initial visit were not significantly more likely to have a subsequent de-escalation by 6 month follow-up; however, they were more likely to have their loop diuretic down-titrated or discontinued.
Abstract 10321: Disrupting the Bag3-hsp70 Complex with the Proposed Cancer Therapeutic Jg-98 is Detrimental for Cardiomyocytes
Authors: Martin Thomas G , Delligatti Christine , Aima Muntu Nitha , Kirk Jonathan A
Published: March 2022

The heat shock protein 70 (HSP70) co-chaperone Bcl-2-associated athanogene-3 (BAG3) is critical for cell viability through facilitating HSP70-dependent protein quality control (PQC). Unfortunately, the same vital functions of BAG3-HSP70 in healthy cells are known to promote cell survival and proliferation in various cancers. Recent promising studies found that disrupting BAG3-HSP70 with the small molecule JG-98 has potent anti-cancer effects in cultured cells and
in vivo
. However, it is unknown what impact this therapy has on other cell types such as cardiomyocytes, where BAG3-mediated PQC is important for function. Using neonatal rat ventricular myocytes (NRVMs), we assessed the impact of JG-98 on cardiomyocyte viability and found apoptosis increased, even at doses 10-100-fold lower than those used with cancer cells. Next, we measured autophagic flux using ammonium chloride to block lysosomal degradation and found flux was reduced with JG-98. To explore mechanism, we assessed expression of BAG3, HSP70, and three other proteins that assemble with the complex during autophagy (HSPB5, HSPB8, SYNPO2). We found BAG3, HSPB8, HSPB5, and SYNPO2 expression decreased at the protein and transcript level with JG-98, while HSP70 expression was not changed. Next, we tested whether the BAG3-HSP70 interaction was important for protein stability of the complex members by treating NRVMs with JG-98 in the presence of cycloheximide to block translation. JG-98 decreased the protein half-life of BAG3, HSPB8, and HSPB5, indicating that protein stability was reduced, while SYNPO2 and HSP70 half-lives were unaffected. As we previously showed BAG3-HSP70 was important for maintaining sarcomere PQC, we next assessed the impact of JG-98 on sarcomere structure. In agreement, we found here that JG-98 caused sarcomere structural disintegration, which was exacerbated with stress. Finally, the detrimental effects of JG-98 on cell viability and sarcomere structure could be partially ameliorated with autophagy induction by rapamycin. Taken together, our findings indicate the importance of BAG3-HSP70 in cardiomyocytes and caution against broadly targeting this complex therapeutically.
Abstract 10330: Intermittent Fasting Interacts with Red Cell Distribution Width to Differentially Improve Cardiometabolic Health
Authors: Horne Benjamin D , Muhlestein Joseph B , May Heidi T , Le Viet T , Bair Tami L , Knowlton Kirk U , Anderson Jeffrey L
Published: March 2022

Introduction:
Intermittent fasting reduces weight and cardiometabolic risk factors. In the WONDERFUL Trial (NCT02770313), intermittent fasting reduced homeostatic model assessment of insulin resistance (HOMA-IR) and the Metabolic Syndrome Score (MSS), with insulin having the largest decline. The red cell distribution width (RDW) measures the dispersion of red blood cell size, is strongly predictive of mortality and major adverse events, and may be a biomarker of general health. This
post hoc
study of subjects from the WONDERFUL Trial examined the interactive effect of intermittent fasting and baseline RDW on changes in insulin, glucose, HOMA-IR, and MSS.

Methods:
Subjects aged 21-70 years who had pre-diabetes, diabetes, or ≥1 other metabolic syndrome factor and modestly elevated LDL-C were enrolled if they were not taking anti-diabetic or statin medications and were free of chronic diseases (N=71; n=38 intermittent fasting, n=33 controls). Subjects were randomized to 24-hour water-only fasting (twice-weekly for 4 weeks followed by once-weekly for 22 weeks) or
ad libitum
eating (control) for 26 weeks.

Results:
Age averaged 49.1±11.1 years and 64.8% were female. Change scores stratified by RDW size distribution (RDW-SD) are shown in the Table. Results were similar when the RDW coefficient of variation (RDW-CV) was used. Intermittent fasting did not change RDW-SD (1.27±9.6 fL vs. control: -0.37±1.76 fL, p=0.34) or RDW-CV (-0.15%±0.55% vs. control: -0.11%±0.45%, p=0.76) over the 26-week trial.

Conclusions:
Compared to controls, intermittent fasting significantly decreased insulin more in subjects with higher baseline RDW than those with RDW ≤median. This differential effect may also apply to changes in HOMA-IR, glucose, and MSS. These findings should be validated and expanded in larger studies since RDW may identify people who would derive the most cardiometabolic benefit from engaging in intermittent fasting.
Abstract 10332: Biventricular Function and Shock Severity Predicts Mortality in Cardiac Intensive Care Unit Patients
Authors: Burstein Barry , Van Diepen Sean , Wiley Brandon , Anavekar Nandan S , Jentzer Jacob C
Published: March 2022

Introduction:
Ventricular dysfunction contributes to shock in cardiac intensive care unit (CICU) patients. We aimed to describe the associations between ventricular dysfunction with in-hospital mortality across the spectrum of shock severity.

Hypothesis:
Patients with biventricular dysfunction (BVD) have higher mortality at each Society for Cardiovascular Angiography and Intervention (SCAI) shock stage.

Methods:
We identified CICU patients from 2007 to 2015 with available echocardiography data within 1 day of admission. Left ventricular systolic dysfunction (LVSD) was defined as left ventricular ejection fraction <40% and right ventricular systolic dysfunction (RVSD) as moderate or greater systolic dysfunction by semi-quantitative assessment; BVD included the presence of both LVSD and RVSD. Predictors of in-hospital mortality were determined after adjustment using multivariable logistic regression.

Results:
We included 3,158 patients with a mean age of 68.2±14.6 years; 51.8% had acute coronary syndromes. LVSD was present in 22.3%, RVSD in 11.8%, and 16.4% had BVD. Hospital mortality increased with SCAI shock stage and was incrementally higher in patients with LVSD, RVSD and BVD across SCAI shock stages (Figure); patients with BVD had higher mortality in each SCAI shock stage. After adjustment, there was no difference in in-hospital mortality for patients with LVSD or RVSD versus those without ventricular dysfunction (p >0.05), but BVD was independently associated with higher in-hospital mortality (adjusted HR 1.815, 95% CI 1.237-2.663, p = 0.0023). Adding ventricular dysfunction to SCAI shock stage increased discrimination for hospital mortality (AUC 0.784 vs. 0.766, p <0.001).

Conclusions:
Among patients admitted to the CICU, BVD was independently associated with higher hospital mortality after adjustment for shock severity. Echocardiographic assessment may augment clinical risk stratification using the SCAI shock classification.
Abstract 10337: Initiative for Timely Acquisition of ECGs in Non-ICU Hospital Areas
Authors: Patel Arjun S , GALVIS Jensen , Ruggero James , Schanz Olivia , Ho Truong-An , Jain Deepanjali , Peterson Sara , Mehta Isha
Published: March 2022

Introduction:
In-hospital patients are a unique patient population with numerous co-morbidities and often atypical presentations for common cardiac problems. Delay in obtaining STAT ECGs on non-ICU (Intensive Care Unit) floors can have consequences ranging from delays in patient care to catastrophic morbidity and mortality for delayed diagnosis and treatment.

Hypothesis:
We hypothesize that there is high variability in the timely acquisition of obtaining inpatient EKGs in non-ICU areas regardless of whether there is a STAT or routine indication.

Methods:
We retrospectively reviewed 75 randomly selected non-ICU inpatient encounters for ECGs between January 2020 and March 2021. Of the 75 cases, 46 encounters met the criteria as non-ICU ECG encounters. The final data set included 24 routine ECG orders and 22 STAT ECG orders. Data gathered included time stamps for time of order, intended time for order to be completed, completion time and upload time in the EMR (electronic medical record).

Results:
STAT ECGs took a median of 1 hour and 42 minutes with times from the first and third quartiles ranging from 36 minutes to 2 hours and 58 minutes. Routine ECGs took a median of 3 hours and 17 minutes with times from the first and third quartiles ranging from 1 hour and 17 minutes to 4 hours and 30 minutes (Graph 1).

Conclusion:
Our results confirm that the acquisition of inpatient EKGs is highly variable and often delayed. Inpatient acquisition of ECGs should be standardized for patient safety and optimal outcomes. A protocol driven and multidisciplinary approach should be implemented to improve timely ECG acquisition.
Abstract 10340: Higher Prevalance of Non-Group 1 Pulmonary Hypertension in Admissions Among Cancer Survivors with Worse In-Hospital Outcomes- A Nationwide Analysis
Authors: Rizvi Bisharah , Shanker Srija , Isufi Mimoza , Nepal Ashish , Joseph Deepu , Singla Tanvi , Mohammad Aamer , Gandhi Zainab , Desai Rupak
Published: March 2022

Introduction:
Pulmonary hypertension (PH) in cancer patients is an underrecognized problem. It can be secondary to malignancy, medications, thromboemboli in lung, and underlying cardiac or lung disease. Outcomes of PH in cancer survivors have not been studied before. The objective of this study is to study the prevalence and impact of Non-group 1 PH on admissions among cancer survivors.

Methods:
The National Inpatient Sample (October, 2015 to 2017), was used to identify all adult hospitalizations among cancer survivors with PH using ICD-10 codes. Primary outcome were prevalence and demographics of PH in cancer survivors. Secondary outcomes were in-hospital mortality and healthcare resource utilization.

Results:
Of 6,003,538 weighted nationwide admissions of cancer survivors, 4.7% (282,810) had non-group 1 PH. The prevalence of PH was higher in patients with prior cancers compared to other admissions (4.7% vs. 3.3%, p<0.001). It was higher in females than males (5.1% vs. 4.3%). Most common in blacks (5.9%), followed by whites (4.7%), Native American (4.1%), Asian or Pacific Islander (3.8%), others (3.7%) and Hispanics (3.3%)
(Fig. 1)
. Hypertension, Diabetes, smoking, obesity, renal failure, congestive heart failure, valvular heart disease and chronic pulmonary disease were higher in PH group. In-hospital outcomes in cancer survivors with vs. without PH showed significantly higher all-cause inpatient mortality in PH group (OR1.34, 95% CI=1.31-1.37, p<0.001) with fewer routine discharges (39.3% vs. 52.1%, p<0.001), higher transfer rate to short-term hospital, and other facilities (skilled nursing care/intermediate care facility), higher home health care requirement, prolonged hospital stay (4 vs 3 days), and higher cost ($10,325 vs. $9163) per admission.

Conclusion:
This is the first large-scale study to demonstrate the higher burden and worse in-hospital outcomes of non-group 1 PH in cancer survivors. Early diagnosis and treatment is necessary.
Abstract 10353: Independent Validation of the Ecg Risk Score for Sudden Death Risk Stratification in Pediatric Hypertrophic Cardiomyopathy
Authors: Walinder Osterberg Anna , Beausejour-Ladouceur Virginie , Stephenson Elizabeth A , Mital Seema
Published: March 2022

Background:
Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death (SCD) in children and young adults. An ECG risk score tested in a Swedish cohort of 155 children with HCM had 97% sensitivity, 80% specificity, 45% positive predictive value (PPV), and 99% negative predictive value (NPV) for SCD risk prediction. Our goal was to validate the ECG risk score in an independent HCM cohort.

Methods:
Phenotype-positive pediatric HCM patients seen at a single center between 1987-2019 with at least 5 years follow-up from diagnosis, or a SCD event within 5 years of diagnosis, were retrospectively identified. First-evaluation ECGs were analyzed by a single operator blinded to patient outcomes. ECG risk score was calculated using QRS electrical axis, amplitude, duration, ST/T-wave abnormalities and QTc duration. The primary outcome was a composite of SCD, aborted sudden cardiac arrest, and appropriate shock from a prophylactic ICD.

Results:
Of 144 eligible patients with a median follow-up 14.6 yrs, 22 experienced SCD events within five years from diagnosis at a median age 12.1 yrs. The ECG risk score in patients experiencing a SCD event was 2-fold higher i.e. 8 (IQR 7-10) compared to the remaining cohort i.e. 4 (IQR 2-8) (p<0.001). An ECG risk score >5 had a sensitivity of 95% (CI 77%-100%), specificity 56% (46%-65%), PPV 28% (24%-33%), NPV 99% (91%-100%), and a receiver operating characteristic area under the curve of 0.76 for its ability to discriminate between patients with and without SCD events (
Figure 1
). Compared to the discovery cohort, the score had strong sensitivity and NPV, but lower specificity and PPV.

Conclusions:
The ECG risk score for SCD risk stratification performed well in an independent Canadian validation cohort but overestimated SCD risk. Futher analysis will determine if inclusion of the ECG risk score can enhance the performance of currently available SCD risk prediction models for pediatric HCM.
Abstract 10354: Socioeconomic Status and Differences in Trends of Atrial Fibrillation Hospitalizations Among Black and Non-Black Adults in the United States
Authors: Rojulpote Chaitanya , Patil Shivaraj , Bhattaru Abhijit , Gonuguntla Karthik , Kela Kashyap , Sheikh Abdul Ahad Ehsan , Buch Tapan , BORUAH Pranjal K
Published: March 2022

Introduction:
Socioeconomic status (SES) and race is closely interlinked. There is limited data regarding trends of atrial fibrillation (AF) hospitalizations in black and non-black adults based on SES.

Methods:
We queried the National Inpatient Sample database from January 2004 to December 2018 to identify patients admitted with AF. We used ICD-9-CM and ICD-10-CM diagnosis codes to identify all patients who were ≥18 years of age and hospitalized with a primary discharge diagnosis of AF. Our cohort was categorized into black and non-black groups, and SES using median household income (MHI) as a surrogate, into low SES (MHI 0-50) and high SES (MHI 51-100). AF hospitalizations per 1 million US population were calculated using US census population ≥18 years of age for each year. We estimated AF hospitalizations per 1 million blacks and non-blacks and trends in AF hospitalizations of black and non-black adults stratified by SES utilizing MHI. Cochran Armitage Test was utilized to estimate temporal trends.

Results:
Total admissions for AF per 1 million adults in the US population has increased (Figure 1). Among patients hospitalized with AF, the proportion of black adults is increasing. In those of low SES, both black and non-black patients have had increases in AF hospitalizations. However, in those of high SES, non-black patients have had steady improvement while black patients have remained at about the same rate of hospitalizations from 2004 to 2018 (Figure 2).

Conclusions:
Trends of AF hospitalizations have increased or not improved in low and high MHI-SES black adults, respectively. Identifying causes of these health disparities can improve healthcare quality in black adults with AF.