bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10620: Real-World Use of Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Heart Failure and Hypertension Initiating Sodium Zirconium Cyclosilicate: The Optimize Study
Authors: Agiro Abiy , Amin Alpesh , Mu Fan , Young Joshua A , Cook Erin E , Lemus Wirtz Esteban , Brahmbhatt Yasmin Ghanshyam , Betts Keith A , Pollack Charles
Published: March 2022

Introduction:
Renin-angiotensin-aldosterone system inhibitors (RAASis) in patients (pts) with heart failure (HF) and hypertension (HTN) are associated with a reduced risk of death or disease progression, but increased risk of hyperkalemia (HK) with RAASis may lead to discontinuation and reduced benefit. This real-world study evaluated RAASi use patterns in pts who initiated sodium zirconium cyclosilicate (SZC) for HK.

Methods:
Adult (≥18 years) outpatients who initiated SZC (index date) while on RAASis were retrospectively identified from a large US claims database (Jan 2018 to Jun 2020). Analyses were conducted among all pts with HK and separately in those with HF or HTN. Outcomes included the proportion of pts with a new RAASi script (different or refill RAASi within 90 days of ending their index RAASi) and median time from index to RAASi discontinuation. A multivariable logistic regression assessed predictors of a new RAASi script among all pts.

Results:
Of 589 pts who initiated SZC during RAASi therapy (mean age 61.0 years, male 65%), 487 (83%) received a new RAASi script post index. In the HF (n=149) and HTN (n=538) cohorts, 120 (81%) and 446 (83%) received a new RAASi script. At index, the most common RAASi prescribed were ACE inhibitors (51%) and ARBs (42%). Among pts with a new RAASi script, median time from index to RAASi discontinuation was not reached (
Figure
), whereas in pts with no new RAASi script, median time from index to RAASi discontinuation was 29 days. Significant predictors of a new RAASi script (vs no new RAASi script) after SZC initiation were fewer prior hospitalizations (adjusted OR 0.77; 95% CI 0.60-0.98;
P
<0.05) and fewer ED visits (0.78; 0.63-0.97;
P
<0.05).

Conclusions:
Consistent with clinical trial findings, >80% of pts on RAASi therapy who initiated SZC for HK had a new RAASi script; similar results were observed in pts with HF or HTN. Pts with inpatient and ED visits may require additional follow-up care to encourage continuation of RAASi therapy.
Abstract 10623: Validation of Embolic and Bleeding Risk Scores in Patients with Atrial Fibrillation and Cancer
Authors: Cespon-Fernandez Maria , Raposeiras Roubin Sergio , Abu-Assi Emad , Fernandez-Sanz Tamara , Muñoz-Pousa Isabel , Melendo Viu Maria , Cabanas-Grandio Pilar , Íñiguez-Romo Andrés
Published: March 2022

Introduction:
Atrial fibrillation (AF) is common among cancer patients. Anticoagulation can reduce the risk of stroke and systemic embolism in AF patients. However, anticoagulation in patients with cancer can be difficult given unpredictable changes in thrombosis and bleeding risk. Although CHA
2
DS
2
-VASc and HAS-BLED are useful, their predictive performance in patients with cancer is unknown.

Hypothesis:
CHA
2
DS
2
-VASc and HAS-BLED scores in AF patients with cancer could lead to misclassification.

Methods:
Overall, 16,056 AF patients between 2014 and 2018 were followed during a median follow-up of 4.9 years, including 1,137 with cancer history. We used C statistic and Brier score for assessing the performance of both scores.

Results:
Discrimination, assessed with C statistics (assuming death as a competing risk), was similar between cancer and non-cancer anticoagulated patients. However, in non-anticoagulated patients, c-statistic of CHA
2
DS
2
-VASc was poor and significantly lower in non-cancer patients. The overall precision of the CHA
2
DS
2
-VASc score was good throughout the follow-up (Brier score <0.1), both in patients with and without cancer history. Regarding to HAS-BLED score, calibration and discrimination were poor in cancer patients, although without significant differences in comparison with non-cancer patients. In non-anticoagulated cancer patients and in those with active cancer, the embolic risk of CHA
2
DS
2
-VASc score = 1 was similar to CHA
2
DS
2
-VASc score ≥ 2. Only AF patients with cancer and CHA
2
DS
2
-VASc score = 0 presented a truly low risk of embolic events (negative predictive value 100%). A HAS-BLED score > 3 did not identify AF patients with cancer at higher bleeding risk.

Conclusions:
In AF patients with cancer, neither the CHA2DS2-VASC score nor the HASBLED score were useful for predicting embolic and hemorrhagic events, respectively. However, a CHA
2
DS
2
-VASc score 0 is useful to identify low embolic risk patients with AF and cancer.
Abstract 10627: Benefits of Icosapent Ethyl in Patients with Prior Peripheral Artery Disease: REDUCE-IT PAD
Authors: Bhatt Deepak L , Steg Philippe G , Miller Michael , Brinton Eliot A , Jacobson Terry A , Tardif Jean-Claude , Ketchum Steven , Juliano Rebecca , Jiao Lisa , Copland Christina , Doyle Ralph , Ballantyne Christie M ,   REDUCE-IT Investigators
Published: March 2022

Introduction:
REDUCE-IT found significant benefit in 8179 statin-treated patients randomized to icosapent ethyl (IPE). Whether that benefit extends to patients with peripheral artery disease (PAD) was unknown.

Methods:
The primary endpoint was time to cardiovascular (CV) death, myocardial infarction (MI), stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary endpoint was CV death, MI, or stroke. Total (first plus recurrent) events were also assessed. PAD was an inclusion criterion in the established CV disease cohort. Prespecified and
post hoc
analyses by baseline history of PAD history were performed.

Results:
Of 5785 (70.7%) REDUCE-IT patients enrolled with established CV disease, 688 had PAD. IPE demonstrated statistically similar risk reduction in first (interaction P [p
int
]=0.58) and total (p
int
=0.78) primary endpoints in patients with established CV disease with or without PAD, though PAD patients had higher first (placebo: 32.8% with vs 24.5% without PAD) and total (placebo: 162.3 vs 101.7 per 1000 patient-years) event rates. The primary endpoint event rate with PAD was 26.2% with IPE vs 32.8% with placebo (HR 0.78; 95% CI 0.59, 1.03; P=0.08) and total events were 112.8 per 1000 patient-years with IPE vs 162.3 with placebo (RR 0.68; 95% CI 0.48, 0.95; P=0.03) (Figure). Primary endpoint absolute risk reductions (ARR) and numbers needed to treat (NNT) suggest benefit for patients with (ARR 6.6%; NNT 15) and without (6.1%; 16) PAD. Safety did not differ substantially by PAD history and was generally consistent with the overall study.

Conclusions:
In REDUCE-IT, patients with PAD were at very high risk of subsequent ischemic events. IPE provided consistent CV benefit in patients with or without PAD.
Abstract 10630: Perfusable Apparatus for Thick-Tissue Creation and Growth (patch) of Cardiac Tissue
Authors: Dunn Tyler , Nurminsky Katherine , Pitaktong Isaree , He Yusheng Jason , Koljaka Sarah , Dunne Olivia , Ran Stephanie , Shih Wesley , Wang Anya , Matsushita Hiroshi , Rodgers Daniel , Hibino Narutoshi
Published: March 2022

Background:
Cardiac tissue engineering has beendeveloped as apotential alternativetreatment for heart failure. However, current 3D tissues are limited insize and thickness due tothe lack of aneffective vascularizationmethod. We have developed anovel bioreactor systemtocreate viable vascularized cardiac tissue from multicellular spheroids using adigital lightprocessing (DLP)3D bioprinting system.

Methods:
Spheroids were created from induced pluripotent stem cells (iPSC)and cardiacfibroblasts (FB)using special dimple plates for mass production. One centimeter cubic tissueswere created from spheroids using aDLP 3D bioprinted mold with vascular channels. Thetissue was maintained inaperfusionchamber under regulated flow and pressure followingdifferentiationtocardiac tissue and endothelialization.

Results:
Mass productionof large spheroids (35,000/ tissue, diameter of 395.99um +/- 101.15um)was achieved from 170millioniPSCs and 50millionFBs for the creationof 1cm3cardiactissue inabioprinted mold with vascular channels. The cardiac tissues (n=5)were perfused for20days under stable pressure of 17.5+/- 3.05PSI and flow of 5000uL/min+/- 1116.42uL/min.Ondays 10and 20, Alamar blue assays showed viability for all five tissues (Alamar blueintensity: Day 101.57+/- 0.15. Day 202.21+/- 0.19).

Conclusion:
Thick and viable cardiac tissues were created and maintained using a3Dbioprinted vascularized mold and perfusionsystem for maturationand growth invitrofor 20days. This technology will opennew doors for viable invitrocardiac tissue creation.
Abstract 10633: Deep Learning Model Accurately Quantifies LA Volumes on Routine Non-Contrast Chest CTs and Predicts Adverse Outcomes
Authors: Aquino Gilberto , Chamberlin Jordan , Mercer Megan , Kocher Madison , Kabakus Ismail Mikdat , Akkaya Selcuk , Fiegel Matthew , Brady Sean , Leaphart Nathan , Dippre Andrew , Giovagnoli Vincent , Yacoub Basel , Jacob Athira , Gulsun Mehmet , Sahbaee Pooyan , Sharma Puneet , Waltz Jeffrey , Schoepf Joseph , baruah dhiraj , Emrich Tilman , Zimmerman Stefan , Agha Ali , Burt Jeremy R
Published: March 2022

Introduction/Hypothesis:
To develop and validate a deep learning model to automatically segment and measure left atrial (LA) volumes from routine noncontrast chest CTs and evaluate for outcomes prognosis.

Methods:
A prototype AI algorithm, with a conditional variational auto-encoder architecture, was initially developed and trained using training data from 1313 patients (paired CTA and non-contrasted exams; “training group”). Left atrium contours from contrasted cases were used to train the model on corresponding non-contrasted dataset. We then retrospectively evaluated 274 patients (mean age 67.9 years, 54.6% male, 57.2% caucasian) who underwent a routine non ECG-gated, noncontrast chest CT for coronary artery calcium or lung cancer screening for validation of the AI model (“validation group”). Outcomes included heart failure (HF) hospitalization and new-onset atrial fibrillation within 5 years. Simple logistic regressions with appropriate univariate statistics were used for modelling outcomes.

Results:
In the validation group, there was excellent correlation between AI and expert results with a LA volume index (LAVi) intraclass correlation coefficient of 0.950 (0.936-0.960). Bland-Altman plot demonstrated that the AI underestimated LAVi by a mean 5.86 mL/m2. AI-LAVi independently predicted new-onset atrial fibrillation (AUC = 0.855, OR = 1.12, 95% CI 1.08 - 1.18; p<0.0001). AI-LAVi was independently associated with HF hospitalization (AUC = 0.903, OR = 1.08, 95% CI 1.04 - 1.13, p = 0.0009).

Conclusion:
In this large validation cohort, AI for automated measurement of LA volume on routine noncontrast chest CTs had excellent agreement with manual quantification. AI-LAVi is independently predictive for new-onset atrial fibrillation and HF hospitalization within 5 years.
Abstract 10634: Out with the Old: Transvenous Extraction of Leads Older Than 15 Years
Authors: Phan Francis , Sanghai Saket , Sandhu Uday G , Verdick Christopher , Gray Andrew , Krebsbach Angela , Jessel Peter , Henrikson Charles
Published: March 2022

Background:
Lead dwell time is the single strongest predictor of failure and complications in transvenous lead extraction.

Objectives:
To report the success rate and complications of transvenous lead extractions with implant dwell time of at least 15 years.

Methods:
Procedural and patient data were prospectively collected into a database. The excimer laser was the primary method for lead extraction with use of mechanical rotational sheaths and femoral snares at operator discretion.

Results:
A total of 443 patients between 2011-2020 underwent lead extraction (707 leads) primarily for infection or device failure at our high-volume center. 40 patients with 69 leads >15 years old were included in this cohort (Table 1). Mean patient age was 53.5 +/- 18.5 years, 67.5% were male. Mean lead dwell time was 19.3 +/- 4.2 years. 35 of 40 (87.5%) patients had successful extraction of all leads (62 of 69 leads - 89.9%). The 5 patients without fully successful extractions resulted in 7 abandoned leads or lead fragments (mean lead age 19.6 +/- 2.3 years). 2 of these patients had abandoned leads (3 total) that were clinically significant. One patient experienced right atrial appendage perforation requiring surgical repair and recovered well. One patient experienced new complete heart block requiring 2 minutes of CPR but did well thereafter. There was no procedure-related mortality.

Conclusions:
Despite challenges posed by older leads, very old leads can be safely and effectively extracted with low complication rates.
Abstract 10644: Impact of Cardiopulmonary Bypass Surgery on Myocardial Perfusion Assessed by Ultrafast Power Doppler: A Human Proof-of-Concept Study
Authors: Nguyen Minh B , Zhang Naiyuan , Mertens Luc L , Barron David , Baranger Jerome , villemain olivier
Published: March 2022

Introduction:
Inadequate myocardial coronary perfusion is a major cause of cardiac dysfunction in several clinical settings including congenital heart disease and cardiopulmonary bypass surgery (CPB). Blood flow to the myocardium (i.e. coronary perfusion) is primarily controlled by the coronary microvasculature (vessels < 500 μm) which plays a key part in coronary perfusion autoregulation. Until recently, direct quantitative coronary perfusion assessment had been infeasible due to limitations in spatial and/or temporal resolution of clinical imaging modalities. The study objective is to assess if ultrafast ultrasound-mediated power Doppler (PD) can approximate changes in myocardial perfusion in humans.

Methods:
We used a 6.9 MHz linear array probe connected to a programmable ultrafast ultrasound scanner (Verasonics Vantage®). We included 7 neonates with transposition of the great arteries (TGA) and acquired epicardial ultrafast acquisitions immediately before and after CPB (arterial switch operation) via open chest. The acquisitions were acquired at 2000 fps (PRF=10000Hz, 5 sources). Tissue clutter was separated from coronary signals with a sliding spatiotemporal filter. PD was measured as a representative of blood volume that scales with hematocrit. Fractional moving blood volume (FMBV) was calculated to normalize the PD signal: mean PD divided by the PD of the ventricular blood pool, a region with 100% vascular amplitude.

Results and Conclusions:
The FMBV post-operatively increased by a factor of two compared to pre-operative assessment, a reflection of hyperemia. These values returned to baseline on repeat assessment prior to discharge. Our findings suggest that ultrafast PD is a reliable tool in approximating changes in myocardial perfusion in the operating room and beyond. Thus, ultrafast power Doppler can be utilized to quantitatively assess the impact of CPB on coronary perfusion in humans.
Abstract 10651: Identification of Allele-Specific Gene Expression in Association with Blood Pressure
Authors: Keshawarz Amena , Huan Tianxiao , Joehanes Roby , Yao Chen , Liu Ching-Ti , Demirkale Cumhur , Ramachandran Vasan S , Cupples L Adrienne , Levy Daniel
Published: March 2022

Introduction:
Risk of hypertension is explained by both behavioral and genetic factors that may act on transcriptomic mechanisms to affect blood pressure variability.

Methods:
Whole genome sequencing and RNA sequencing data were obtained on 1,671 Framingham Heart Study (FHS) participants (mean age 54±13 years). Allelic expression of heterozygous SNPs was measured and allelic imbalance was identified using a binomial test. SNPs with significant allelic imbalance were evaluated in linear regression to test the association between the reference/total allele count ratio and 1) systolic blood pressure (SBP), and 2) diastolic blood pressure (DBP). Models were adjusted for age, sex, BMI, and family structure.

Results:
At a Bonferroni-corrected p-value<6.4E-8, we identified 20,890 SNPs with significant allelic imbalance at MAF>0.01. Prior GWAS have identified >2,000 SNPs associated with SBP, DBP, or hypertension; we identified allelic expression imbalance of 60 SNPs (in 44 genes) that were reported in GWAS to be associated with SBP, and of eight SNPs (in two genes) that are associated with DBP. These genes were significantly enriched for the immune effector process pathway (p=1.4E-7). Fifteen SNPs were located in promoter or promoter-flanking regions, while the remaining SNPs were located in protein-coding regions. Seventeen SNPs were also
cis
-eQTLs, of which four transcripts also were associated with SBP or DBP in the FHS cohort.

Conclusion:
We identified ASE linked to blood pressure. Our results suggested that novel transcriptomic regulatory mechanisms involving allelic imbalance at specific SNPs may play a role in blood pressure regulation.
Abstract 10661: Association Between Blood Transfusion and Mortality During Hospitalization for Acute Decompensated Heart Failure
Authors: Methvin Laura , Kearing Stephen , Brugger Cassandra , Hanlon Emma , Martinez-Camblor Pablo , Dodge Shayne , Gilstrap Lauren
Published: March 2022

Introduction:
Limited data exist on the association between blood transfusion (BT) and mortality among patients hospitalized with acute decompensated heart failure (ADHF) and anemia. There is good reason for this clinical equipoise because the benefit of enhanced oxygen delivery to tissues must be balanced with the consequences of additional volume in a hypervolemic state. The aim of this study is to determine the association between BT and short and long-term mortality among patients hospitalized with ADHF and anemia.

Methods:
Using EMR data from an academic referral hospital, we created a cohort of patients admitted between January 2012 and December 2019 for ADHF and anemia. Patients with ACS or transfusion dependence were excluded. BT was determined using CPT codes. Inverse probability weighting was used to balance patients who did and did not receive BT across relevant demographic, laboratory and clinical variables. We then used logistic regression and Cox proportional hazard modeling to determine the association between BT and in-hospital, 90-day, and 1-year mortality.

Results:
There were 2,114 patients admitted with ADHF and anemia; 490 (23%) of these patients received BT. BT was associated with 1.5-fold increased risk of in-hospital mortality (95% CI [1.05-2.16], p=0.03). Among those who survived to discharge, there was no difference in 90-day mortality (OR 1.18 [0.88-1.59], p=0.26) or 1-year mortality (OR 1.04 [0.85-1.29], p=0.69) between those who received transfusion and those who did not (Figure 1).

Conclusions:
Among patients admitted with ADHF and anemia, BT was associated with higher in-hospital mortality. Among those who survived to discharge, in-hospital BT was not associated with any difference in long-term mortality. Additional work is needed to understand ideal transfusion thresholds. Our work suggests the importance of judicious use of BT in patients admitted with ADHF and advises that BT is associated with a worse prognosis during admission.
Abstract 10665: Pulse Wave Velocity Measured at End-Diastole Underestimates Aortic Stiffness
Authors: Reddy Anilkumar K , Entman Mark L , Taffet George E
Published: March 2022

Introduction:
Aortic stiffness (AS) is assessed using pulse wave velocity (=

distance (D) between two aortic sites
/
foot-to-foot transit time of pressure or velocity pulse (ffPTT) between the sites

) which is considered as “gold standard”. But, PWV varies with cyclic pressure in the normal aorta and PWV measured at end-diastole underestimates AS. This underestimation is greatest when aorta is the stiffest.

Hypothesis:
We hypothesize that PWV measured at diastole is lower than that measured at systole and that PWV should be measured over the entire cardiac cycle for better representation of AS.

Methods:
We measured pressures invasively with a dual sensor catheter (0.46 mm dia) at two descending aortic sites (25 mm apart) in normal rats. We measured blood velocities noninvasively with two Doppler probes placed at aortic arch and abdominal aorta. The pressure and blood velocity signals were acquired simultaneously (at baseline & post-esmolol admin). From the two pressure signals we measured PWVsp (at dicrotic notch; end-systolic fiducial marker) and PWVdp (at end-diastole; foot fiducial marker). PWVd (end-diastole; foot) was measured from the two blood velocity signals.

Results & Conclusions:
We plotted the PWV versus blood pressure. We found that the slope of aPWVsp > the slope of aPWVdp indicating that PWV varies with blood pressure within the cardiac cycle. We also found that slope of aPWVd < aPWVdp because, D used to calculate PWVdp is fixed at 25mm, whereas D used to calculate aPWVd was estimated as the distance between Doppler probe tips on the surface of the skin (aortic arch curvature was not accounted for). In conclusion, a more representative AS can be assessed through 1. PWV measurement at systole & diastole within the cardiac cycle of a noninvasively measured vessel wall motion (a pressure signal surrogate) where the systolic and diastolic fiducial points can be identified, and 2. use of two aortic sites on the straight part of the descending aorta for better estimating of D.
Abstract 10680: Unsupervised Machine Learning Clustering Identifies Phenotypes of Optimal Candidates in Mitraclip Patients
Authors: Chao Chiehju , Wu Han-Lun , Seri Amith , Shanbhag Anusha , Rayfield Corbin , Wang Yuxiang , Smith Sean , Fortuin Floyd D , Sweeney John , Eleid Mackram F , Alkhouli Mohamad , RIHAL Charanjit , Holmes David R , Pollak Peter , El Sabbagh Abdallah , Lester Steven , Shen Win K , Patel Bhavik , Arsanjani Reza
Published: March 2022

Introduction:
Unsupervised machine learning (ML) can provide insight into a dataset without significant expert time for annotation and labeling, but was never used to assess the heterogeneous MitraClip population.

Hypothesis:
We hypothesized that unsupervised k-means ML could identify prognostically-distinct phenogroups in MitraClip patients without a priori knowledge of the dataset.

Methods:
Patients who underwent MitraClip (June 2014-September 2020) at Mayo Clinic sites were identified from the Mayo institutional NCDR database for baseline and follow-up data. Variables with ≥ 50% missing data were excluded. A k-means algorithm was used for clustering analysis. Input variables were grouped according to 4 distinct k-means determined clusters. Kaplan-Meier survival analysis was used to assess the survival of each cluster.

Results:
A total of 389 consecutive patients were included in the final analysis, and 95 unique variables were used. The mean age was 80.3±8.7 years; 256 (65.8%) were male. The mean STS MV Replace score was 9.1±5.7. Fifty-five (14.5%) patients died during the mean follow duration (185 days). Kaplan-Meier analysis showed significant survival differences among clusters (Figure 1). The cluster (cluster 2, n=120) with best survival performance (all-cause mortality 3.3%) had features of non-calcified mitral leaflets, nonischemic cardiomyopathy, and less than moderate tricuspid regurgitation. Cluster 3 (n=66) had the worst survival performance (all-cause mortality 27.3%) and opposite features than cluster 2.

Conclusions:
Unsupervised ML can identify distinct phenotype clusters with prognostic significance in MitraClip patients. Patients with non-calcified mitral leaflets, nonischemic cardiomyopathy, and less than moderate tricuspid regurgitation are intrinsically different from other MitraClip patients and should be considered the potential optimal candidates.
Abstract 10683: Association Between Triglycerides and Incident Chronic Kidney Disease in Diabetics Across Stages of Albuminuria
Authors: Rizk John , Soohoo Melissa , Hashemi Leila , Arif Yousif , Hsiung Jui-Ting , Marroquin Maria , Edward Jessica , Streja Elani
Published: March 2022

Background:
Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Urine albumin to creatinine ratio (UACR) and albuminuria are critical components in CKD staging as well as a hallmark of diabetic kidney disease. We sought to evaluate the relationship of triglycerides (TG) with incident CKD in diabetic non-CKD patients, stratified by level of albuminuria, which has been less studied thus far.

Methods:
This study comprised of 99,705 diabetic non-CKD veterans with data on TG and MetS components. The incident CKD outcome was defined as multiple eGFR measurements of <60 mL/min/1.73m
2
at least 90 days apart. Using Cox proportional hazards models, we evaluated the association of TG with incident CKD, adjusted for case-mix characteristics, laboratory values including hemoglobin A1c, and stratified by baseline albuminuria categories.

Results:
The mean±SD age was 63±10, with a median [IQR] for TG of 147[99, 222] mg/dL, and UACR <30 mg/g for 76% of patients. We observed a slight linear association between TG and incident CKD after adjustment for case-mix and laboratory variables among patients with Alb A1 and A2 stages (<30 and 30-300 mg/g) (ref: TG 120-<160 mg/dL) (Figure). While low TG were associated with a lower risk of incident CKD, elevated TG ≥240 mg/dL trended towards a higher risk of event. Among Alb A3 patients (>300 mg/g), we observed an inverse U shape, where elevated TG ≥240 mg/dL trended towards a lower risk of incident CKD after adjustment.

Conclusion:
Elevated TG were associated with a higher risk of incident CKD in diabetic non-CKD patients with normal microalbuminuria. Patients with higher levels of albuminuria trended towards a lower relationship. Additional study is warranted to investigate the mechanism behind diabetic kidney disease risk with consideration for levels of albuminuria.
Abstract 10693: Noninvasive Assessment of Contractility and Compliance of the Left Ventricle in Children: Myocardial Stiffness Measured Throughout the Cardiac Cycle by Shear Wave Imaging
Authors: villemain olivier , Baranger Jerome , Mroczek Dariusz , Mertens Luc L , Nguyen Minh , Chaturvedi Rajiv
Published: March 2022

Background:
Intrinsic myocardial stiffness (MS) is load-independent, unlike most parameters to assess LV systolic and diastolic function. Pre-clinical studies have found good correlation between 1) peak-systolic MS and contractility (or ESPVR); 2) end-diastolic MS and compliance (or EDPVR). Shear wave imaging (SWI) by ultrafast ultrasound imaging allows MS measurement throughout the cardiac cycle.

Methods (Fig 1):
Five children with LV pressure-overload (LV-PO; 2 aortic stenosis, 3 coarctation) were studied during cardiac catheterization and there were 5 age-matched controls. Interventricular septal MS was measured by SWI every 100ms during the cardiac cycle, pre- and post-balloon dilation. ESPVR and EDPVR were assessed by pressure-volume loops by a pressure catheter and real-time 3D-echo volumes.

Results (Fig 2):
Peak-systolic MS was higher in LV-PO (22.7±6.7 kPa) than controls (8.4±2.8 kPa; p<0.01) and compared to end-diastolic MS (LV-PO 4.8±1.7 kPa, control 1.3±0.8 kPa; p<0.01). End-diastolic MS was correlated with LV end-diastolic pressure (r=0.74). Relief of PO did not change the peak MS in the LV-PO (p=0.88). Correlations between peak-systolic MS and ESPVR (r=0.72), and between end-diastolic MS and EDPVR (r=0.79) were confirmed.

Conclusions:
Non-invasive MS is a load-independent measure of LV systolic contractility and diastolic compliance in children.
Abstract 10696: Cerebral Blood Flow and Vascular Function Are Impaired in Adults Who Report Adverse Childhood Events
Authors: Rodriguez Miguelez Paula , Looney Jacob , Blackburn Marsha , thomas jeffrey , Pollock Jennifer , Harris Ryan A
Published: March 2022

Introduction:
Adverse childhood events (ACEs), including abuse, neglect, or severe household dysfunctions, have been associated with the development of premature cardiovascular disease (CVD) during adulthood. Acute and intense emotional stress leads to structural changes in the brain that reduce cerebral blood flow, specifically in the medial prefrontal cortex (mPFC). In response, the body releases stress hormones and mediators that cause peripheral vascular dysfunction, a prognostic marker of CVD. Whether or not ACEs predispose adults to reductions in mPFC blood flow and associated peripheral vascular dysfunction has yet to be investigated.

Hypothesis:
This study sought to test the hypotheses that ACEs contribute to reductions in mPFC blood flow and associated peripheral vascular dysfunction.

Methods:
Fifty-three young adults (34 ± 3 yrs), with no evidence of overt CVD, were divided into a high (HiA) and no (NoA) ACE group based on their self-reported ACE questionnaire score: HiA: ACE score ≥ 4 (n=17) or NoA: ACE score = 0 (n=36). Near-infrared spectroscopy was utilized to assess blood flow (tHb), O
2
delivery (O
2
Hb), and O
2
consumption (HHb) in the mPFC. Peripheral vascular function was determined using the flow-mediated dilation (FMD) technique.

Results:
The HiA group had a significantly (
p
=0.009) lower tHb compared to the NoA (56 ± 4 vs. 69 ± 3 μM, respectively). In addition, O
2
Hb and HHb were significantly (
p
≤0.04) reduced in the HiA when compared to the NoA. Likewise, FMD was significantly (
p
=0.001) lower in HiA (6.3 ± 0.7%) compared to NoA (9.4 ± 0.5%). Significant associations were also identified between ACEs and tHb (
r
= -0.574;
p
=0.001) and between tHb and FMD (
r
=0.477;
p
=0.021).

Conclusion:
For the first time, we have documented that blood flow in mPFC is reduced and vascular function is impaired in adults who reported ACEs compared with adults who did not report ACEs. Notably, individuals exposed to a greater number of ACEs present with lower cerebral blood flow and higher CVD risk. Future studies are warranted to evaluate possible mechanisms underlying these dysfunctions as well as potential therapeutic interventions to reduce as well as to prevent the exacerbated CVD risk observed in individuals exposed to ACEs.
Abstract 10717: Role of Integrin Signaling in Pulmonary Arterial Hypertension
Authors: Lemay Sarah-eve , Montesinos Mónica S , Grobs Yann , Shimauchi Tsukasa , Breuils Bonnet Sandra , Martineau Sandra , Huang Xinqiang , Dowling James E , Lu Min , Ray Adrian S , Paulin Roxane , Potus François , Provencher Steeve , BOUCHERAT Olivier , Bonnet Sebastien
Published: March 2022

Pulmonary arterial hypertension (PAH) is characterized by progressive obstruction and decreased compliance of pulmonary arteries (PA), leading to right ventricular (RV) failure and premature death. It is now recognized that, like cancer cells, PA smooth muscle cells (PASMCs) exhibit exaggerated proliferation and resistance to apoptosis in response to increased PA stiffness caused by extracellular matrix (ECM) remodeling. Integrins (members of the cell adhesion receptors superfamily) are known to promote cell proliferation, survival, hypertrophic growth and fibrosis, which are key elements in the progression of PAH. Therefore, we explored integrins expression and its effects on PA remodeling and RV failure.

By RNA sequencing, we demonstrated a significant upregulation of integrin signaling pathways. Among all integrins, the fibronectin binding integrin (FiBI) family was the most abundant in PASMCs and RV fibroblasts (RVFbs) isolated from PAH patients (n=5). By western blot (WB) we showed that integrin expression is significantly changed in distal PAs, PASMCs and RV from PAH patients (n=6-8) compared to controls (n=5-8). Similarly, increased expression was found in monocrotaline (MCT) and pulmonary artery banding (PAB) rats (n=20, p<0.05.)
In vitro
, pharmacological inhibition of FiBI decreases PAH-PASMCs proliferation (WB: PCNA and Ki67 labeling; p<0.05) and resistance to apoptosis (WB: Survivin and Annexin V labeling; p<0.05). These effects were associated with a decreased activation of the AKT/mTOR pathway. In cardiomyocytes and human RVFbs, FiBI inhibition decreased phenylephrine-induced hypertrophy (Phalloidin labeling; p<0.001) and TGFβ1-induced RVFbs activation (WB: αSMA, CTGF, FN and Col1; p<0.05) and proliferation (Ki67; p<0.05).
In vivo
, pharmacological FiBI inhibition improved PAs remodeling (EVG staining) and RV function (SV, CO, TAPSE, S-Wave, as assessed by echocardiography and right heart catheterization) in MCT rats with established PAH (n=20; p<0.05).

We demonstrated that upregulation of fibronectin binding integrins and broad spectrum integrin inhibition resulted in improvements in distal PAs remodeling and RV failure. These results suggest that integrins play an important role in the pathophysiology of PAH.
Abstract 10721: Exposure of Computer-Based Contrast Induced Nephropathy Risk Tool to Operator During Percutaneous Coronary Intervention
Authors: Gold Matthew E , Sun Deyu , Burkhart Ryan , Gold Daniel , Kong Nathan , Oliveira Lucas , Blair John
Published: March 2022

Introduction:
Contrast induced nephropathy (CIN) is one of the main causes of morbidity, mortality, and increased financial burden in high risk patients undergoing percutaneous coronary intervention (PCI). Although intravenous hydration is routinely used to prevent CIN among patients undergoing PCI, the optimal amount is not defined.

Hypothesis:
The current trial aims to determine whether a computer-based contrast induced nephropathy (CBCIN) risk tool, in addition to suggested standard hydration strategies exposed to the primary operator, results in lower rates of CIN and improved death and combined death/rehospitalization in patients undergoing PCI.

Methods:
Patients were recruited prospectively at the cardiac catheterization laboratory at the University of Chicago Medical Center in the inpatient and outpatient setting. Eligible participants were determined to be at-risk for CIN and included adult patients with either a reduced baseline eGFR (<60 ml/min/1.73 m2) or patients with diabetes mellitus, hypertension, heart failure or age >75 years. It is up to the operator’s discretion whether to use this information and hydration strategy. Operators then completed a survey of their experience.

Results:
There were 21 patients analyzed in this study. The average age was 73 and included 8 (38.1%) women. Operators reported a change in their treatment plan in 12 (57.1%) cases for a change to the contrast plan and 10 (47.6%) cases for a change in IV hydration plan. Use of the CBCIN risk tool led to an increase in the perception of CIN risk in 14 cases (66.7%), decreased time to calculate CIN risk in 16 (76.2%) cases, and increased adoption of CIN risk into the case in 17 (81.0%) cases.

Conclusions:
This is a preliminary description of an ongoing study showing that the CBCIN tool changed operator behavior, improved perception of CIN risk, and improved workflow. Future randomized studies are needed to determine whether CBCIN use translates into improved renal and clinical outcomes.
Abstract 10729: Parametric T1 Mapping for Quantitative Differentiation of Cardiac Metastases and Thrombus on Cardiac Magnetic Resonance
Authors: Park Christine , Plitt Anna , Tak Katherine , Kim Jiwon , Steingart Richard , Weinsaft Jonathan W , Chan Angel T
Published: March 2022

Introduction:
Cardiac magnetic resonance (CMR) is widely used to assess cancer patients (pts) with cardiac masses (C
MASS
); contrast uptake on late gadolinium enhancement (LGE) is a reference to distinguish cardiac metastases (C
MET
) from thrombus (C
THR
). Parametric T1 mapping is an alternate approach to quantify pre and post-contrast tissue properties: Utility of T1 mapping to differentiate C
MET
and C
THR
is unknown.

Hypothesis:
Among cancer pts with cardiac masses, pre and post contrast T1 mapping can distinguish C
MET
from C
THR
.

Methods:
The population comprised cancer pts with C
MASS
; etiology was classified by presence (C
MET
) or absence (C
THR
) of enhancement on LGE-CMR. T1 mapping entailed a MOLLI pulse sequence acquired in co-registered locations (pre, post contrast) within C
MASS
as localized on cine-CMR - mobile masses (prohibiting T1 evaluation) were excluded. T1 analyses were performed blinded to clinical, LGE, cine-CMR data.

Results:
94 C
MASS
pts (54±18 yo, 53% M) with an array of cancers (29% sarcoma, 19% GI, 13% GU) were studied, among whom 81% (n=76) had C
MET
and 19% (n=18) C
THR
on LGE-CMR. Cardiac structure, function, and clinical characteristics were similar (p=NS) between groups, but location differed with C
THR
right-sided [RA 94%, RV 6%) and C
MET
variable (LV 29%, RV 25%, LA 30%, RA 32%). On T1 mapping, C
MET
had longer pre-contrast T1 (1355±359 vs. 1135±195 msec, p=0.001) and shorter post contrast T1 (437±196 vs. 755±199 msec, p<0.001), with resultant higher ECV (41±19 and 10±6%, p<0.001) than did C
THR
(
Figure
). ROC analyses showed high overall diagnostic performance for T1 mapping to differentiate C
MET
from C
THR
based on AUC (pre: 0.71, post: 0.88, ECV: 0.92 [all p<0.01): Maximum partition cutoffs for pre (1284msec) post (578msec) and ECV (22%) yielded good sensitivity and specificity to delineate C
MASS
subtypes.

Conclusion:
Among cancer pts with cardiac masses, T1 mapping - including pre and post contrast tissue characterization - can distinguish C
MET
from C
THR
.
Abstract 10731: Evaluation of Patient Perspectives on the Use of Mobile Apps to Support Heart Failure Management
Authors: Sivakumar Bridve , Lemonde Manon , Stein Matthew , Mak Susanna , Al-Hesayen Abdul , Farmer Anna , Arcand JoAnne
Published: March 2022

Background:
Adherence to diet and medical therapies are key to improving heart failure (HF) outcomes; however, nonadherence is common. While mobile apps may be a promising way to support patients with adherence via education and monitoring, little is known about HF patient opinions regarding adoption of apps for HF management; which is critical to understand for these tools to be successfully developed, implemented, and adopted.

Objective:
To determine patients’ needs, motivations and challenges on the use of mobile apps to support HF management.

Methods:
A qualitative descriptive study using focus groups (n=4,60 minutes) was conducted among HF patients (aged ≥18 yrs, smartphone/tablet users, on stable medical therapy without hospital admission for ≥ 6 months) from outpatient HF clinics in Toronto, Canada. The Diffusion of Innovation theory informed a ten-question interview guide. Interview transcripts were independently coded by two researchers and analyzed using content analysis.

Results:
Nineteen HF patients (65 ± 10 yrs, 12 men) identified technology and app use behaviours, opportunities and challenges across six main themes: 1)‘Patient usage of technology’, many patients already used technology for daily activities and monitoring health; 2) ‘Patient views on adopting new technology’, some patients reported being early adopters of technology, while others would wait; 3) ‘Factors impacting technology use by patients’, included access to accurate information, easy and accessible user-interface; 4) ‘Providing patient support through access to information and self-monitoring’, apps could provide education on HF-related content (e.g., diet, medication, exercise, symptoms); 5) ‘Facilitating connection and communication’, apps could help information sharing with healthcare providers and connect with other patients; 6) ‘Patient preferences of app features’, app features such as reminders for medication, and visuals to show changes in HF symptoms were favoured.

Conclusions:
HF patients perceive several benefits to app use for HF self-management. Capitalizing on the opportunities apps offer may maximize their adoption by patients and support adherence to diet and medical therapies to improve HF outcomes.
Abstract 10734: Assessment of Cardiovascular Disease and Mortality Among Black Patients with Gout
Authors: chandrakumar Harshith P , Puskoor Anoop V , Chillumuntala Seeta , Sharif Sara , Cepeda Mora Diego , Gupta Tanuj , Tadayoni Ashkan , Celiker Pelin , Yakoubovitch Stephanie , Tsai Andrew , Chiu Courtney , Kazi Anan , Frielich Michael , Saleh Ahmad , Moon Seung Jae , Cruickshank Kingsley , Katz Julie , Salciccioli Louis , McFarlane isabel M
Published: March 2022

Introduction:
While the association between gout and cardiovascular disease (CVD) has been extensively studied, scarce data is available for the Black population. We aimed to assess, in a predominantly Black urban population with gout, the prevalence of traditional CVD risk factors, CV outcomes, and the strength of the association between gout and CVD after adjusting for CVD risk factors.

Hypothesis:
Black patients with gout have higher CVD rates compared to a matched cohort without gout.

Methods:
Cross-sectional analysis of data obtained from the EMR of gout patients followed at our primary care clinics. Patients were identified by ICD codes and compared to age, sex and race matched non- gout cohort. Descriptive data was obtained, and logistic regression used to assess the strength of association between gout and CVD, before and after adjustment for CVD risk factors including obesity, DM, HTN, dyslipidemia and smoking.

Results:
There were 471 patients with gout with a mean age of 63.7 ± 0.5 years (mean ±SEM); 89% were Black, 63% were men, mean BMI was 31.3 ± 0.4 Kg/m
2
. HTN, DM and dyslipidemia were present in 89%, 46% and 52% respectively.Compared to controls, patients with gout had significantly higher rates of angina, arrythmia, CAD/stents, MI, CABG, CVA, and PVD. The odds ratio (OR) for CVD = 4.5 (3.3-6.2) (95% CI), p<0.001 and OR =2.9 (1.9-4.5), p<0.001 before and after adjustment for CVD risk factors respectively. There was a significantly higher mortality rate of 6.2 in gout vs 2.6 in the non- gout cohort, p <0.01.

Conclusion:
Gout in a predominantly Black population confers three times the CVD risk and overall mortality compared to a race, age and sex-matched cohort.This risk appears greater compared to previously published data in whites (OR 1.25-1.55) (Choi HK et al Circulation 2007;116:894-900). Further research is needed to confirm our findings and to develop interventions to reduce morbidity and mortality among these vulnerable patients.
Abstract 10735: Conduction Abnormalities and Pacemaker Implantation in Patients with Radiation-Associated Cardiac Disease
Authors: Xu Samantha , Zheng Wynne , Ospina Susan , Donnellan Eoin , Griffin Brian P , Johnston Douglas , Kapadia Samir R , Wilkoff Bruce L , Desai Milind Y
Published: March 2022

Introduction:
We sought to study prevalence of conduction disease and permanent pacemaker (PPM) in patients presenting with radiation-associated cardiac disease (RACD) and its impact on long-term survival.

Methods:
We studied 699 patients with documented RACD (prior chest radiotherapy at a mean of 22 years prior) evaluated at a single center from 1998-2018. Conduction abnormalities and PPM at baseline were recorded, along with cardiac procedures performed during follow-up. Death was the primary endpoint.

Results:
Patients were divided into 4 groups: 1) no procedure during follow-up 2) 1 valve or coronary artery bypass grafting (CABG) or 1-valve+CABG surgery 3) Multivalve+/-CABG+/-aortic/pericardial surgery and 4)Trans catheter aortic valve replacement (TAVR). Relevant characteristics and outcomes are shown in Table. In total, 183 patients had a PPM (82 [45%] implanted during follow-up). Over a mean follow-up of 5±4 years (range 0-21 years), 370 patients (53%) patients died. On survival analysis, presence of PPM (HR 1.26 [1.03-1.54], p=0.03) was independently associated with higher long-term mortality; 109 (60%) patients with PPM died in the long-term vs. those without261 (51%, log-rank p-value=0.03).

Conclusion:
RACD patients have a high rate of mortality during longer-term follow-up, despite a low calculated preoperative risk. In addition, they have a high rate of conduction abnormalities with a high proportion requiring PPM, including at baseline, irrespective of need for a cardiac procedure. Presence of a PPM was independently associated with long-term risk of mortality.
Abstract 10742: Implication of the Importins KPNA2 and KPNB1 in Pulmonary Arterial Hypertension
Authors: Lemay Sarah-eve , Awada Charifa , Toro Victoria , Romanet Charlotte , Orcholski Mark , Paulin Roxane , Provencher Steeve , Bonnet Sebastien , BOUCHERAT Olivier , Potus François
Published: March 2022

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by the elevation of mean pulmonary arterial pressure and resistance, culminating in right ventricular failure and premature death. Pulmonary artery smooth muscle cells (PASMCs) isolated from PAH patients exhibit cancer-like phenotypes such as exaggerated proliferation and resistance to apoptosis, key elements contributing to pulmonary arteries (PA) remodeling. Taking benefits of our previously published proteomic study realized on PASMCs isolated from PAH and control patients, we identified the upregulation of importins proteins, namely KPNA2 and KPNB1. The importins contribute to the nucleocytoplasmic shuttling of macromolecules and transcription factors. Cancer studies highlighted the contribution of the KPNA2 and KPNB1 complex in the pro-proliferative and anti-apoptotic phenotypes of cancer cells. Given the cancer-like phenotype of PAH cells, we hypothesized that increased KPNA2-KPNB1 expression promotes PASMCs survival and adverse PA remodeling.We confirmed that KPNA2 and KPNB1 expression is increased in PASMCs and distal PAs isolated from PAH patients compared to controls (western-blot, n=8-9, p<0.05). Similarly, we reported an increased expression of KPNA2-KPNB1 in 3 preclinical models of PH: hypoxic mice, monocrotaline rats and Sugen-hypoxia (Su-Hx) rats (n=8-12, p<0.05).
In vitro
, molecular (siRNA) and pharmacological (Ivermectin) inhibition of KPNA2-KPNB1 complex decreases PAH-PASMCs proliferation (WB: PCNA; IF: Ki67 and EdU incorporation labeling) and resistance to apoptosis (WB: Survivin; IF: Annexin V labeling) (n=5, p<0.5). Those results are associated with decreased expression of NFAT, NF-kB and STAT3.
In vivo
, Ivermectin improved PA remodeling (EVG staining) and hemodynamic parameters as assessed by echocardiography (PAAT, TAPSE) and right heart catheterization (RVSP, SV, CO) in Su-Hx rats (n=20, p<0.05). We demonstrated 1) an increased expression of the importins KPNA2 and KPNB1 in PAH, 2) targeting KPNA2-KPNB1 reverses adverse PA remodeling and PH development. Thus, the repurposing of Ivermectin could represent a novel therapeutic strategy from the laboratory bench to patients’ bedside to reverse PAH development.