bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9452:
Artificial Intelligence for Predicting Human Age in ECG
Authors: CHUO ZHI-XUAN , Chang Ruey-Kang
Published: April 2022

Background:
Previous research has shown that age is highly correlated to ECG findings, and machine learning (ML) can be used to predict the age of a patient based on the findings on a 12-lead ECG. We structured a state-of-the-art deep ML model to correlate with age, which may be used to detect changes following the trends.

Methods:
We composed a 40-layers self-definite ResNet model. The model was trained with 10-second 12-lead ECG of 25,915 records from 23,625 patients. We then validated the accuracy of age prediction using 6,479 records from a separate dataset. Once the model was validated, we tested the model using randomly selected ECG records, including 20 records from a weight loss center and 20 records from cardiology clinic patients.

Results:
After the model was developed and validated, we tested it on 40 patients with ages 52.2 ±13.7 years, ranging from 17 to 76 years. The mean absolute error (MAE) was 8.0 years and the root mean square error (RMSE) was 9.7 years. Among these 40 patients, 21 patients (52.5%) had ECG-predicted age within 7 years difference from their chronological age. When we selected the age range of 42-75 years old (29 records), the result of MAE decreased to 7.4 years, with 70% of the prediction results within 7 years and the RMSE decreased to 9.1 years. The average difference between chronological and ECG-predicted ages decreased to 3 years when serial recordings of ECG of the same patients were used.

Conclusions:
Using ML models, ECGs can be used to correlate with a patient’s age and may be useful to track the changes longitudinally. “ECG-predicted age” may be an important measurement to follow the trend for comprehensive health assessment over time.
Abstract 9470: The Relative Risk of Cerebrovascular Accident in Patients With Von-Willebrand Disease
Authors: Olagunju Abdulbaril , Mihyawi Nawfal , Fath Ayman R , Forst Beani , Bhattarai Bikash , Yeneneh Beeletsega T
Published: April 2022

Introduction:
Von Willebrand factor (vWF) is essential in platelet adhesion and aggregation. High concentration of vWF is associated with cerebrovascular accidents (CVA); however, it is yet unclear if its deficiency could protect against CVA. This study aims to compare the prevalence and relative risk (RR) of CVA in patients with and without vWD.

Methods:
Discharge data of the National Inpatient Sample (NIS) from 2009 to 2014 were analyzed and records for vWD and CVA were identified using ICD-9 codes. Log-binomial model was used to estimate the RR of CVA in patients with and without vWD after adjustment for CVA risk factors.

Results:
A total of 224,475,443 weight adjusted hospital discharge sample of patients, including 82,809 patients with vWD, were identified. The prevalence of CVA was lower in patients with vWD than those without vWD (1.31% vs 2.04%), with a RR of 0.64 (95% CI: 0.60-0.68) (table 1). Adjusted RR for CVA risk factors was 0.71 (95% CI: 0.67-0.76) (table 2).

Conclusion:
Patients with vWD showed a lower risk of developing CVA when compared to those without vWD, this lower RR persisted after controlling for other CVA risk factors. These findings suggest that vWD could be protective against CVA, and vWF might be a potential therapeutic target that requires further investigation in individuals at high risk of developing CVA.
Abstract 9477: Relation Between Coronary Artery Calcium Score and Clinical Outcomes After Percutaneous Coronary Intervention in Stable Coronary Artery Disease
Authors: Komaki Soichi , Ishii Masanobu , ikebe sou , Kaichi Ryota , Takae Masafumi , Mori Takayuki , Toida Reiko , Kurogi Kazumasa , Yamamoto Nobuyasu , Tsujita Kenichi , Kaikita Koichi
Published: April 2022

Introduction:
Recently, some consensus on high bleeding and thrombotic risk has been reported in the management of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). However, none of the currently available risk scores includes coronary artery calcification (CAC) score. The usefulness of the assessment of coronary artery calcium on the net adverse clinical event (NACE) in patients with stable CAD undergoing PCI remains understudied. This study aimed to evaluate the association between the CAC score measured by multidetector computed tomography (MDCT) and clinical outcomes after percutaneous coronary intervention (PCI) in stable CAD patients.

Methods:
We conducted a retrospective observational study including 134 consecutive patients who underwent MDCT and were scheduled for the first elective PCI. The patients were divided into 2 groups based on the CAC score [low (≤ 400) and high (> 400) CAC score]. High bleeding risk was assessed using the Academic Research Consortium for high bleeding risk (ARC-HBR) and the Japanese Circulation Society High Bleeding Risk (JCS-HBR) criteria. The clinical outcome was NACE that was defined as a composite of all-cause death, myocardial infarction (MI), stroke, target lesion revascularization (TLR), stent thrombosis, and major bleeding. According to the Bleeding Academic Research Consortium (BARC) definition, major bleeding was defined as BARC 3 and 5.

Results:
The high CAC score group was significantly associated with NACE than the low CAC group (22.0% vs 7.5%, P = 0.019). The Cox regression analyses showed that CAC score but not HBR-positive was a significant prognostic factor for NACE (HR, 3.27; 95% CI, 1.14-10.4; p < 0.028, HR, 1.12; 95% CI, 0.37-3.21; p = 0.834, respectively). The Kaplan-Meier survival curves showed that the high CAC group had a higher frequency of NACE events compared with the low CAC group (p = 0.012).

Conclusions:
The association of high CAC score with NACE including thrombotic and bleeding events were observed in patients with stable CAD, indicating that high CAC was independently related to being a predictor for NACE after PCI.
Abstract 9486: Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults
Authors: Zhou Zhen , Ryan Joanne , Ernst Michael E , Zoungas Sophia , Tonkin Andrew M , Woods Robyn L , McNeil John J , Reid Christopher , Curtis Andrea J , Wolfe Rory , Wrigglesworth Jo , Shah Raj C , Storey Elsdon , Murray Anne , Orchard Suzanne G , Nelson Mark R
Published: April 2022

Background:
The neurocognitive effect of statins in older adults remains uncertain.

Objectives:
To investigate the associations of statin use with cognitive decline and incident dementia among older adults.

Methods:
This analysis included 18,846 participants (aged ≥65 years) from a randomized trial of aspirin (ASPirin in Reducing Events in the Elderly, ASPREE). At baseline, participants had no experience of a CVD event, major physical disability, or diagnosed dementia, and were followed for a median (IQR) of 4.7 (3.5-5.6) years. Outcome measures included incident dementia and its subclassifications (probable Alzheimer’s disease [AD]; mixed presentations), changes in domain-specific cognition (global cognition, memory, language and executive function, psychomotor speed) and the composite of these domains. We examined the associations of baseline statin use with dementia using Cox proportional-hazards models, and with cognitive change using linear mixed-effects models, adjusting for confounders. The role of statin lipophilicity was also examined.

Results:
Compared with no statin, baseline statin use was not associated with incident dementia (adjusted HR [95%CI]: 1.16 [0.97-1.40]), probable AD (1.33 [1.00-1.77]) or mixed presentations of dementia (1.06 [0.82-1.35]) (
Table 1
). Nor was it associated with changes in composite or domain-specific cognitive function scores over time (
Table 2
). No differences were found in any outcomes between hydrophilic and lipophilic statin users (
Tables 1 & 2
).

Conclusions:
In healthy adults aged ≥65 years without diagnosed dementia, statin therapy over 4.7 years was not associated with incident dementia or cognitive decline.
Abstract 9489: Echocardiographic Characteristics, Cardiovascular Factors, and Disease-Directed Therapy Do Not Explain Differences in Covid-19 Related Hispanic Outcomes
Authors: Wong Joseph Isaac S , Sadek Ramy , Mehrabani Armeen , Koppula Anthony , Soverow Jonathan
Published: April 2022

Introduction:
Severe coronavirus disease 2019 (COVID-19) is associated with cardiovascular injury and disparate outcomes in different ethnic groups. However, the reason for this difference has not been elucidated.

Methods:
A retrospective cross-sectional study was done on adult COVID-19 patients at a single center from April 2020 to January 2021. Mortality, length of stay, mechanical ventilation use, and intensive care unit (ICU) status were compared across demographic groups, echocardiographic indices, and COVID-19-specific treatments.

Results:
One hundred fifty patients were included. In univariate analysis, elevated cardiac biomarkers, COVID-19 directed therapies, and elevated right-sided pressures were associated with higher mortality, mechanical ventilation use, length of stay, and ICU admission. Multivariable logistic regression predicted higher mortality for Hispanic ethnicity (odds ratio, OR, 6.7) even when adjusting for advanced age (OR 5.3), mechanical ventilation use (OR 18), and right ventricular systolic pressure (OR 1.1 per 1mmHg). There were no differences in underlying comorbidities, echocardiographic indices, cardiac biomarkers, or treatments between Hispanic and non-Hispanic patients.

Conclusions:
Despite being a younger cohort, Hispanic patients had a higher rate of mortality even when controlling for age, biomarkers, and echocardiographic indices. This suggests Hispanic ethnicity is an independent risk factor for mortality in COVID-19 infection, highlighting an important health inequity that warrants further investigation.
Abstract 9509: Is Left Ventricular Lead Placement at Site of Latest Mechanical Activation Associated with Cardiac Resynchronization Therapy Outcomes? Results of a Meta-Analysis
Authors: Allen Lapointe Nancy M , Ali-ahmed Fatima , Dalgaard Frederik , Kosinski Andrzej S , Sanders Gillian D , Al-Khatib Sana M
Published: April 2022

Introduction:
CRT outcomes with image-guided left ventricular (LV) lead placement within the LV segment of latest mechanical activation have been assessed in several randomized controlled trials (RCTs) with equivocal results, possibly due to variable achievement of concordant LV lead placement in the image-guided and comparator arms. We conducted meta-analyses to assess CRT outcomes associated with concordant LV lead placement.

Methods:
A systematic literature review was performed to identify RCTs and prospective observational studies of CRT from October 2008 through October 2020 that reported outcomes in those with LV lead placement at or adjacent to the site of latest mechanical activation (concordant) versus those with LV lead placement distant to the site of latest mechanical activation (discordant) as determined by any imaging method. Two independent reviewers screened titles and abstracts then reviewed full text for inclusion/exclusion. One reviewer abstracted data and a second over-read for accuracy. Meta-analyses for death, death or HF hospitalization, and changes in LVESV and LVEF were performed using random effects models.

Results:
Among 5715 citations identified, 9 papers from 8 studies (including 4 RCTs) were selected that included 1004 patients with concordant LV lead placement and 380 with discordant LV lead placement. Mean patient age ranged from 66 to 68 years, 82% were male, and 64% had ischemic cardiomyopathy. Segment of latest activation was determined by speckle tracking echocardiography (STE) in 7 (88%) studies. Meta-analyses demonstrated statistically significant lower all-cause mortality or HF hospitalization and reduction in LVESV with a concordant LV lead (Figure). There were trends toward lower all-cause mortality and increased LVEF.

Conclusion:
A concordant LV lead, as determined primarily by STE, was associated with better CRT outcomes. Further study of feasible methods to achieve concordance in clinical practice is needed.
Abstract 9510: How Dose Body Water Composition Change Around Cardiopulmonary Bypass Surgery of Children with Congenital Heart Disease? -Assessing by Bioelectrical Impedance Analysis
Authors: Obinata Haruka , Yasukochi Satoshi , Numata Ryusuke , Yonehara Kohsuke , Konuma Takeshi , Akazawa Yohei , Takei Kohta , Takigiku Kiyohiro
Published: April 2022

Introduction:
Although the management of body water balance on cardiac surgery with cardiopulmonary bypass (CPB), especially in children, is essential, little is known how body water composition changes around CPB. We aim to evaluate a change of intracellular (ICW), extracellular (ECW), and total body water composition (TBW) before and after CPB, using bioelectrical impedance analysis (BIA).

Hypothesis:
There is a possibility that the fluid distribution and water balance change depends on intraoperative water balance management and age. Then we investigate the impact of (1) intraoperative water balance management and (2) age at operation on changes of body water composition.

Methods:
The forty-five children weighing over 5Kg (Age ranges 3mo-11yo) were enrolled to this study. The body water balance was measured at before, at immediately after CPB, at 1 day, and at 2 days, respectively. Each parameter was compared by the factor of intraoperative water balance and that of age at operation.

Results:
The minus water balance during CPB results in significant shortage of ICW which not fully recovered by 2 days after CPB (Figure A). Cases >2yo developed a decrease of ICW and ECW 2 days after CPB, while those <2yo increased (Figure B).

Conclusions:
The body water composition significantly changes along CPB than expected. Care must be taken to prevent a harmful dehydration by controlling intraoperative water balance management and by age on the basis of BIA.
Abstract 9515: Heterogeneity of Benefit on Quality of Life With an Invasive versus Conservative Strategy for Chronic Coronary Disease. Results From the ISCHEMIA Trial
Authors: Arnold Suzanne , Jones Philip , Maron David J , Mark Daniel B , Reynolds Harmony R , Bangalore Sripal , Newman Jonathan D , Chen Jiyan , Harrington Robert A , Cohen David J , Stone Gregg W , Hochman Judith S , Spertus John
Published: April 2022

Background:
The ISCHEMIA trial recently showed that, on average, patients with chronic coronary disease (CCD) and at least moderate ischemia randomized to an invasive strategy (INV) reported less angina and better quality of life (QOL) than those treated conservatively (CON)—an effect sustained through follow-up. To better support shared decision-making for individual patients, we explored the heterogeneity of treatment benefit of the INV vs CON strategy within the ISCHEMIA trial.

Methods:
Disease-specific QOL was assessed with the Seattle Angina Questionnaire (SAQ; scores range 0-100, higher=less angina/better QOL). An ordinal (proportional odds) model for 1-year SAQ summary score (SAQ SS) produced estimates of the odds of better QOL with randomization to INV vs CON, with potential heterogeneity of treatment benefit explored via interactions between patient factors and treatment. The final model included both significant interactions (accounting for multiple testing) and main effects.

Results:
Among 4617 patients with CCD from 37 countries randomized to INV vs CON treatment (mean age 64 ± 10 y, 23% women, 40% diabetes), mean SAQ SS was 74.1 ± 18.9 at baseline and 85.7 ± 15.6 at 1 year (p<0.001). Patients with lower baseline SAQ SS (i.e., more angina) and younger patients derived greater symptomatic treatment benefit from INV management (model-based interaction p=0.005 and p=0.004, respectively; Figure). No other patient factor was associated with a differential treatment effect. In the final model, female sex and diabetes were also associated with worse 1-year QOL, independent of treatment.

Conclusion:
Using data from a large multinational randomized trial, we found that younger patients and those with more angina at baseline derived greater QOL benefit from INV management. As the primary benefit of revascularization in CCD is symptom improvement, this model could be used to better inform individual patient’s decision-making for initial treatment.
Abstract 9534: Proteomic Signature of Right Ventricular Failure in Pulmonary Arterial Hypertension
Authors: Yokokawa Tetsuro , Shimauchi Tsukasa , Bonnet Sandra B , Potus francois , Paulin Roxane , Provencher Steeve , Bonnet Sebastien , BOUCHERAT Olivier
Published: April 2022

Background:
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease leading to pulmonary artery pressure elevation and right ventricular (RV) failure. RV failure is the principal determinant of adverse outcomes in PAH patients and represents a major unmet medical need. Thus, a better understanding the pathogenesis of RV failure is mandatory. In this study, we used an unbiased proteomics approach to identify the molecular players engaged in RV failure development caused by PAH.

Methods and Results:
Proteomics analysis (nano-LC-MS/MS) was performed using control (autopsy, normal RV function, n=10), compensated (cRV, patients with RV hypertrophy and preserved cardiac index>2.2L/min/m
2
, n=10), and decompensated RV (dRV, PAH patients who died from RV failure, n=10). We identified 424 differentially expressed proteins between the dRV and control patients (p<0.05). Of these 424 proteins, 245 were upregulated and 179 were downregulated in the dRV. Using GO enrichment analysis and protein-protein interaction network, we found that upregulated proteins were significantly enriched in pathways involved in immune system and extracellular matrix organization, whereas downregulated proteins were mainly involved in muscle structure development, metabolism, and RNA splicing. To confirm the robustness and sensitivity of the expression changes observed in our proteomic data sets, expression levels of 3 selected proteins implicated in RNA splicing, namely heterogeneous ribonucleoprotein particle (HNRNP)-A1, -C1/C2 and -U, were measured by Western blotting. Consistent with the results of proteomics, these HNRNP proteins were markedly downregulated in dRV compared to cRV or controls (p<0.05). Similar results were observed in RV tissue samples from monocrotaline-injected and pulmonary artery banding-subject rats (n=7-10, p<0.05).
In vitro
, we demonstrated that knockdown of HNRNPA1 using siRNA prevents phenylephrine-induced cardiomyocyte (H9c2) hypertrophy, as assessed by immunostaining of F-actin and expression of
Nppb
. Further experiments are currently performed to decipher the role of HNRNPs in RV failure.

Conclusions:
Our data open novel perspectives for understanding molecular mechanisms of RV failure progression in PAH.
Abstract 9544: Physical Activity in Individuals With Hypertrophic Cardiomyopathy: Baseline Data From the Prospective "Lifestyle and Exercise in Hcm" (live-hcm) Study
Authors: Lampert Rachel , Ackerman Michael J , Marino Bradley S , Burg Matthew , Ainsworth Barbara , Salberg Lisa , Tome Maite , Balaji Seshadri , Ho Carolyn , Czosek Richard J , James Cynthia , Emery Michael , Cooper Robert , Bos Martijn , Geske Jeffrey B , Choudhury Lubna , Etheridge Susan P , Lal Ashwin K , Ware James S , Dubin Anne M , Gray Belinda , Molossi Silvana M , Maron Martin S , Saberi Sara , Jacoby Daniel L , Eidem Benjamin W , Harmon Kimberly , Hall Kevin , Olshansky Brian , Link Mark S , Law Ian , Saarel Elizabeth V , Estes N A , Maron Barry , Cannom David S , Li Fangyong , Briske Kaylie , Simone Laura , Barth Cheryl , Concannon Maryann , Day Sharlene
Published: April 2022

Introduction:
Safety of vigorous exercise for individuals with appropriately-treated HCM remains debated. Physical activity practices in this population have not been described. The objective of this report is to describe physical activity pattern in HCM patients. Long term follow up which is ongoing will determine safety of vigorous exercise.

Methods:
The NIH-funded LIVE-HCM study prospectively enrolled individuals age 8-60 years with clinically overt HCM or patients with a positive genetic test for sarcomeric HCM. Participants (or parents, for children) answered surveys describing activity patterns. Vigorous exercise was defined as > 6 METS for > 60 hours per year. Clinical and demographic data were derived from medical record review.

Results:
Among 1798 participants, 745 (41%) reported exercising vigorously, including 296 competitive athletes, with 59 at high-school or college varsity level, 770 (43%) were exercising at moderate, and 283 (16%) at low levels. Of those working, 6% described jobs more active than walking, including 16 in protective services, and 11 in sports/coaching. Clinical/demographic data including imaging characteristics and treatments, are shown in Table, and were mostly similar amongst the exercise-groups.

Conclusions:
Many patients with HCM are engaged in vigorous exercise including competitive athletics. Prospective follow-up of this cohort is ongoing. Comparison of arrhythmic outcomes outcomes in vigorous exercisers vs moderate/low level exercisers will help determine the safety of exercise in HCM patients.
Abstract 9550: Sex and Ethnicity Specific Burden of Coronary Artery Calcium Among Middle-Aged and Older Adults: Multi-Ethnic Study of Atherosclerosis
Authors: Whelton Seamus P , Dzaye Omar , Razavi Alexander C , Dardari Zeina , Villines Todd , Budoff Matthew J , Blumenthal Roger S , McClelland Robyn , Blaha Michael J , Nasir Khurram
Published: April 2022

Introduction:
Detection of coronary artery calcium (CAC) at a low score is the ideal phase of the atherosclerotic process to start primary prevention therapies. A better understanding of how the proportion of individuals with zero, low, or moderate/high CAC changes with age, sex, and race/ethnicity may aid in determining the optimal age to perform general CAC scoring before there is a severe burden of atherosclerosis.

Methods:
We calculated the proportion of individuals with 1) CAC ≥1 and CAC ≥100 based on population percentiles from 6,110 participants without diabetes from the Multi-Ethnic Study of Atherosclerosis (MESA) who had a CAC scan at Visit 1 (2000-02).

Results:
There was an approximately 12 year age difference for when 25% of men had CAC ≥1 compared to CAC ≥100 (<45-51 years old vs 58-63 years old) compared to an approximately 14 year age difference for women (54-59 years old vs 69-75 years old). Women had a 50% prevalence of CAC ≥1 by age 69 years old (71 for Black women vs 67 for White women) compared to age 57 years old for men (62 for Black men vs 53 for White men). White men had a 50% prevalence of CAC ≥100 at age 68 years old, which was between 8-15 years younger than men of other races/ethnicities while women did not have a 50% prevalence of CAC ≥100 until age 80 years or older. In order to have at least a 25 to 50% probability of CAC ≥100, testing should be considered at ages of 55-64 for White men, 65-74 for men of other races/ethnicities and White women, and 75-84 years old for women of other races/ethnicities.

Conclusion:
Women developed CAC ≥1 approximately 12 years later in life than men. White men developed CAC ≥100 at a much younger age than men of other races/ethnicities, while a majority of women did not develop CAC ≥100 until age ≥80 years old. These findings may provide additional information to aid in the clinician-patient decision making process on the ideal age to perform CAC scoring, especially for those individuals who wish to rule out the presence of a moderate or high CAC score.
Abstract 9555: A Mean Hemoglobin A1c Level of 7,5% is a Cliff Value for the Development of Cardiovascular Events in Diabetic Patients
Authors: Soejima Hirofumi , Morimoto Takeshi , Okada Sadanori , Matsumoto Chisa , Nakayama Masafumi , Jinnouchi Hideaki , Masuda Izuru , Waki Masako , Saito Yoshihiko , Ogawa Hisao
Published: April 2022

Background:
We sought to evaluate whether there was a difference in the incidence rate of cardiovascular event (CVD) among different hemoglobin (Hb) A1c levels in diabetic patients without a history of atherosclerotic events.

Methods:
The Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial was a multicenter, prospective, randomized, open label, blinded, end-point study done from 2002 to 2008. After completion of the JPAD trial, we followed up with the patients until 2019. We defined the cardiovascular events as the following: acute myocardial infarction; stable angina; unstable angina; sudden cardiac death; stroke; transient ischemic attack; aortic disease; and peripheral artery disease. Among 2,535 JPAD patients, HbA1c levels of the JPAD patients were recorded on average 8 times. Based on the mean value of HbA1c, we divided the patients into three groups: a High HbA1c Group (n=899, HbA1c ≥7.5%); a Moderate HbA1c Group (n=581, 7.5% >HbA1c ≥7.0 %); or, a Low HbA1c Group (n=1055, 7.0% >HbA1c). We compared the incidence of CVD among the three groups.

Results:
The mean HbA1c (%) was 8.6 in the High HbA1c Group, 7.4 in the Moderate HbA1c Group, and 6.6 in the Low HbA1c Group on registration. During an 11.56-year follow-up, the incidence of CVD was significantly higher in the High HbA1c Group (P<0.0001, Figure) but was not significantly different between the Moderate HbA1c and the Low HbA1c Groups. Cox proportional hazards model analysis revealed that a High HbA1c level (HR, 1.61: 1.26-2.05, P=0.0001) was an independent factor after adjustment for proteinuria ≥±, age ≥65 years, male, body mass index ≥24 kg/m
2
, duration of diabetes ≥7.0% years, medications, eGFR ≥60 ml/min/1.73m
2
, and systolic blood pressure ≥140 mm Hg (Figure).

Conclusions:
Our study demonstrated that HbA1c ≥7.5% was independently associated with the incidence of CVD in diabetic patients without a history of atherosclerotic events while 7.5% >HbA1c ≥7.0 % was not.
Abstract 9561: Loss of Full Length Pumilio 1 Abrogates Gene P27 Silencing-Mediated Cell Proliferation and Secures Mirna-221 Mimics Therapeutics in the Heart
Authors: Wang Peipei , Zhou Yue , Ng Yu En , Richards A Mark
Published: April 2022

Introduction:
MiR-221 mimics have been demonstrated to be cardioprotective and anti-fibrotic in the treatment of myocardium infarction and heart failure. However, miR-221 is a known oncomiR as the upregulation of miR-221 and the downregulation of its target p27 are associated with tumor progression and poor prognosis. Therefore the treatment of miR-221 mimics raise safety concerns.

Hypothesis:
miR-221 fails to trigger P27 mediated neoplastic cellular proliferation due to loss of full length pumilio-1 (FL PUM-1) expression
in vivo
.

Methods:
H9c2, Hela and primary cardiac fibroblasts were used to study the regulations of miR-221 mimics on P27 by RT-qPCR and Western blot, cell proliferation by cell number, CCk-8 and Ki67 staining. The interaction with PUM1 was assessed by siRNA transfection, p27 3’UTR cloning and luciferase reporter assay.
In vivo
2 days after miR-221 mimic (1mg/kg and 4mg/kg)
i.v.
injection in the rats, the liver, heart, kidney and muscle were collected to measure p27 and PUM1 by RT-qPCR and WB. Pum1 cDNA was cloned using primers flanking its start and stop codons, and inserted into pcDNA3.1 vector. 10 colonies from each tissue were sequenced to verify mRNA splicing variants. PUM1 cleavage were verified by the incubations of cathepsin K (CatK) inhibitor odanacatib (ODN).

Results:
in vitro
miR-221 mimics significantly downregulated the expression of P27 and increased cell proliferation. FL PUM1 (140kDa) and isoforms of 105 and 90 kDa were detected. The transfections of siRNAs to knockdown PUM1 but not PMU2 abolished miR-221-mediated effects and direct binding of miR-221 on
p27
3’UTR.
In vivo
following two dosages miR-221 mimic treatments, the expressions of miR-221 increased in the heart, liver, kidney and muscle for 6.8 and 17.3 fold, 33.4 and 506.5 fold, 2.2 and 3.5 fold, and no significant increases respectively. P27 was not affected. FL-PUM1 was not detected in all tissues, but only isoforms. 105 kDa was generated through alternative RNA slicing and 90 kDa by CatK cleavage.

Conclusions:
This is the first study to address the safety concerns with respect to the possible pro-proliferative effects of miR-221 mimic therapeutics in cardiovascular applications. It provides essential insights of the context-dependent nature of miRNA functionality.
Abstract 9565: Quantitative Assessment of Neonatal Brain Perfusion by Ultrafast Power Doppler in the Operating Room
Authors: Aguet Julien , Fakhari Nikan , Nguyen Minh , Mertens Luc L , Barron David , Baranger Jerome , villemain olivier
Published: April 2022

Introduction:
The main challenge with cardiopulmonary bypass (CPB) surgery in newborns with congenital heart disease is to prevent ischemic brain injury impacting on the long-term neurodevelopmental outcomes. To date, no quantitative method is available to adapt the CBP parameters for optimal per-operative cerebral perfusion. Ultrafast power Doppler (UPD) is a new portative bedside technique to map and quantify cerebral perfusion. Our objective was to evaluate UPD for quantifying the variation of cerebral perfusion in neonates during CBP surgery.

Methods:
UPD was performed in 5 newborns with hypoplastic left heart syndrome undergoing a Norwood procedure and 5 age-matched healthy newborns. Using a 6.9 MHz linear array probe (11L, General Electric) connected to a programmable and portable ultrafast ultrasound scanner (Vantage 256, Verasonics Inc.), via a transfontanellar approach, six pre-defined brain imaging planes were acquired in sagittal and coronal views. Assessments were performed pre-operatively, during various perfusions states intra-operatively and 24-48 hours post-operatively. Global and regional cerebral blood volume (CBV) and resistivity index (RI) maps from UPD were obtained.

Results:
The baseline brain perfusion was the same for both groups (p=0.62). During CPB, whole brain and regional CBV decreases more than 50% compared to baseline and reaching approximately 25% of initial CBV during selective brain perfusion and during the final stages of bypass (Figure). RI maps shows intermittent overall decrease of vascular resistivities below 0.5 on bypass and selective brain perfusion before returning to baseline in post-op, reflecting an overall decrease of the cerebral vascular resistance during CPB.

Conclusions:
UPD demonstrates variation in cerebral vascular resistance and blood volume in neonates undergoing CPB surgery. UPD paves the road for optimization of CPB parameters in neonates undergoing cardiac surgery.
Abstract 9580: Impact of Clopidogrel Metabolizer Status on Incidence of Gastrointestinal Bleed
Authors: singh Aditya , Coy Kevin , Schmidtman Daniel , Stys Adam , Stys Tom
Published: April 2022

Introduction:
Clopidogrel is used for secondary prevention of coronary artery disease, stroke, and peripheral vascular disease. Increased doses has been associated with increased odds of gastrointestinal (GI) complications (gastritis, gastric ulcer and bleeding). Effectiveness of clopidogrel is dependent on its conversion to active metabolite by liver enzyme CY2C19.

Hypothesis:
Clopidogrel metabolizer status impacts the incidence of GI bleed.

Methods:
Patients aged >18 years, on clopidogrel and known CYP2C19 status were included in the study. Based on functional copies of CYP2C19 they were divided into two groups slow (poor or intermediate) and adequate metabolizers (normal, rapid, ultra-rapid) and were retrospectively analyzed for documented diagnosis of GI bleed after initiation of clopidogrel.

Results:
A total of 3778 patients were included in the study who were on clopidogrel and had known CYP2C19 status. Of these patients, 74.2% were adequate and 25.8% were slow metabolizers. Overall, there were 332 patients (8.8%) with a documented diagnosis of GI bleed following initiation of clopidogrel. There was no significant difference observed in incidence of GI bleed among slow and adequate metabolizers (8% vs 9.1%, p=0.313).

Conclusions:
Our study demonstrates that the clopidogrel metabolizer status does not appear to have any significant impact on incidence of GI bleeding, which further strengthens the fact that GI bleed is a multi-factorial pathology.
Abstract 9582: Maternal Triglyceride Levels Were Associated with Gestational Hypertension but Were Not Associated with Fetal Growth in Normal Pregnancy
Authors: Hu Wei , Guan Ping , Su Yanling
Published: April 2022

Introduction:
Abundant lipid supply and moderate mobilization of lipid metabolism allow proper nutrients for fetal development during pregnancy. However, knowledge of whether and how lipid levels associated with gestational hypertension and preeclampsia is inconsistent and no reference standards are currently defined for lipid parameters during pregnancy.

Hypothesis:
Higher maternal triglyceride (TG) levels were associated with pregnancy complications and that a wide range of TG levels was sufficient for fetal growth.

Methods:
A case-control study combined with a cross-sectional study. 464 patients with gestational hypertension and/or preeclampsia were pooled into a case group. A total of 1077 women with full-term pregnancies and no pregnancy complications were selected as controls.

Results:
Maternal levels of TG were significantly higher in the case group than in controls in all gestational weeks (12 to 16). Maternal levels of TG, total cholesterol (TC) and low-density lipoprotein (LDL-C) in healthy controls increased gradually and significantly with increasing gestational week, however, these lipid concentrations lost their steady elevating trends with gestational week increases in the case group. Binary logistic regression showed that TG is a risk factor associated with hypertension and/or preeclampsia at gestational weeks 12 to 16 and independent to maternal blood levels of glucose and LDL-C. The odds ratios for gestational complications were 2.24 [95% confidence interval (CI): 1.31 - 3.83], 2.11 (95%CI: 1.35 - 4.13), 2.61 (95%CI: 1.10 - 6.17), 2.45 (95%CI: 1.27 - 4.52) and 2.36 (95%CI: 1.17 - 4.32) respectively in case women with TG levels higher than the 75th percentile of healthy controls at gestational weeks 12 to 16. Of the healthy controls at gestational weeks 12 to 16, quantile regression showed that TG levels were not associated with real-time fetal growth measurements or final birthweight. The reference standards for maternal TG levels were estimated via the 10th, 25th, 50th, 75th, and 90th percentiles by gestational week.

Conclusions:
Maternal TG levels are associated with gestational hypertension and/or preeclampsia, and a wide range of TG levels is sufficient for fetal growth within a given gestational week.
Abstract 9584: Familial Hypercholesterolemia Patient Perspectives and their Alignment With the FH Global Call to Action
Authors: Jones Laney K , Sheldon Amanda , Walters Nicole , Brangan Andrew , Wilemon Katherine A , Salome-Campbell Gemme , Kulchak Rahm Alanna , Gidding Sam , Sturm Amy C
Published: April 2022

Introduction:
Familial hypercholesterolemia (FH) is an inherited disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. The 2020 FH Global Call to Action, produced by international FH global advocacy organizations, individuals with FH, and scientific experts, provides nine recommendations to reduce premature death and the public health burden of FH. We explored alignment of patient and family member perspectives with these recommendations.

Methods:
Interviews and focus groups were conducted with individuals with FH and their family members from multiple U.S. health systems and members of the FH Foundation community to identify barriers to identification, cascade testing, and treatment. Patient-centered perspectives were sought to develop solutions that can be implemented. These perspectives were then examined and classified, according to their alignment to recommendations within the FH Global Call to Action.

Results:
Stories from 75 individuals with FH and family members, who participated in at least one of the qualitative assessments, were analyzed. The table lists the FH Global Call to Action recommendations with patient-centric perspectives abstracted from individuals’ stories. The most common stories and perspectives linked to the recommendations for awareness, screening, diagnosis, testing, and treatment, and family-based care.

Conclusions:
The Global Call to Action recommendations resonate highly with U.S. FH individuals and their family members. Patient-centric perspectives further address the need to prioritize FH as a global public health concern and support FH education and advocacy efforts.
Abstract 9586: Prognostic Impacts of Changes in Right Ventricular Fractional Area Change in Patients with Heart Failure
Authors: Sugawara Yukiko , Yoshihisa Akiomi , Takeishi Ryohei , Ohara Himika , Ichijo Yasuhiro , Hotsuki Yu , Watanabe Koichiro , Sato Yu , Abe Satoshi , Misaka Tomofumi , Sato Takamasa , Oikawa Masayoshi , KOBAYASHI ATSUSHI , Nakazato Kazuhiko , Takeishi Yasuchika
Published: April 2022

Background:
It has been reported that changes in left ventricular ejection fraction (LVEF) is associated with further prognosis in patients with heart failure (HF). We aimed to examine prognostic impact of changes in right ventricular fractional area change (RVFAC) on risk of cardiac event including cardiac death and worsening HF in HF patients.

Methods and Results:
We enrolled consecutive 480 hospitalized patients with decompensated HF and measured RVFAC with echocardiography at discharge (1
st
examination) and post discharge in the outpatients setting (2
nd
examination). RVFAC at 1
st
examination of 480 HF patients were above 35% in 314 (65.4%), 25-35% in 108 (22.5%), and less than 25% in 58 (12.1%) patients. Next, based on RVFAC changes from 1
st
to 2
nd
examination, these patients were categorized into four groups: 1) U-preserved (unchanged and preserved-RVFAC, n=235, 49.0%); 2) Recovered-RVFAC (improvement in at least one category from 1
st
to 2
nd
examination, n=106, 22.1%); 3) U-reduced (unchanged and reduced-RVFAC, n=47, 9.8%); and 4) Worsened-RVFAC (deterioration of at least one category from 1
st
to 2
nd
examination, n=92, 19.2%). There was only a weak correlation between RVFAC change and LVEF change (R=0.16, P<0.01). Multivariate logistic regression analysis revealed that anemia and chronic kidney disease were predictors of Worsened-RVFAC. In the Kaplan-Meier analysis (
Figure
), RVFAC at 1
st
examination was not associated with cardiac event rate. However, RVFAC changes from 1
st
to 2
nd
examination was associated with cardiac event rate. In the multivariable Cox proportional hazard analysis, Worsened-RVFAC was an independent predictor of cardiac event rate (vs. U-preserved-RVFAC, HR 2.25, P<0.01; vs. Recovered-RVFAC, HR 2.75, P<0.01).

Conclusions:
The HF patients with worsened-RVFAC are associated with adverse prognosis. RVFAC changes are important for deciding treatment and predicting prognosis in HF patients.
Abstract 9587: Combined Aortic Regurgitation and Stenosis of the Bicuspid Aortic Valve Increases Ascending Aortic Wall Shear Stress and Left Ventricle Energy Burden
Authors: Sughimoto Koichi , Harada Takumi , Fujiwara Takashi , Barker Alex J , Kabasawa Masashi , Liu Hao
Published: April 2022

Introduction:
The bicuspid aortic valve (BAV) opening pattern and the degree of aortic stenosis (AS) are reportedly associated with the aneurysmal formation in the ascending aorta. Although AS is often accompanied by aortic regurgitation (AR), the combined effect of AR and AS on the wall of the ascending aorta and energy loss of the blood flow are not well understood.

Hypothesis:
We hypothesize that AR along with AS can increase the wall shear stress (WSS) to develop the aneurysm in the ascending aorta and increase the load on the left ventricle (LV).

Methods:
The effects of AR along with AS BAV on the hemodynamic features were assessed using an image-based subject-specific LV-aorta integrated computational model. The computational model was constructed based on an MRI dataset of a 72-year-old healthy volunteer. Four different types of stenosed (52% stenosis) BAV models were created: Type 0, RL fused, RN fused, and LN fused. Then, physiological boundary conditions were given based on a parameter-adjusted 0-1D cardiovascular model of the AS BAV with no AR, mild AR (17% regurgitant fraction (RF)), and severe AR (48% RF) to assess hemodynamic indices such as time-average of WSS in the ascending aorta and pulsatile energy loss index (PELI), an index to estimate energy loss in the aorta.

Results:
Averaged WSS was highest in the severe AR with AS BAV in 4.1±0.2 Pa, followed by the mild AR with AS BAV in 3.1±0.21 Pa, and no AR with AS BAV in 2.7±0.3 Pa. The intra-ventricular flow (LV) showed more disturbed flow in mid-diastole in severe AR with AS BAV. PELI was augmented in mild AR with AS BAV in 0.34±0.05 and severe AR with AS BAV in 0.25±0.06, compared to no AR with AS BAV in 0.19±0.16.

Conclusions:
AR along with AS in BAV has a great impact on increasing the WSS in the ascending aorta and increasing the energy loss of the flow in the aorta. These features imply that advanced AR along with AS in BAV may raise the risk of the development of aortic aneurysm as well as heart failure due to the increased workload on the LV.
Abstract 9605: The Six Minute Walk Test: Right Test, Wrong Interpretation!
Authors: Doyle Mark , Rayarao Geetha , Lacson Roger , Hussain Nasir , Biederman Robert W
Published: April 2022

Introduction:
In patients with pulmonary hypertension (PHTN), after initial hemodynamic assessment, it is common practice to perform the six minute walk test (6MWT). The absolute distance walked represents an integration of pulmonary artery pressure (PAP) and right heart function. Thus, the initial distance walked for each patient is generally used as the benchmark to compare to future 6MWT to assess therapy/prognosis. Here we show that the absolute 6MWT distance (6MWD) is less ambiguously interpreted as the measured impedance between the LV and the aorta.

Methods:
Patients (n=33, 82% F), age 51± 12yrs) with PHTN (>80% WHO I) underwent CMR to assess phasic blood flow through the aorta at the interface to the LV. CMR- phase velocity mapping flow data at single plane (acquisition time: 2min) was used to calculate the previously described and validated LV impedance (IMP
LV
). IMP
LV
was calculated using the formula:

IMP
LV
= (cardiac beat interval; CL) x (mean blood velocity) / (aortic diameter). Systolic PAP was measured during a right heart cath performed within one week of CMR and at the time of 6MWT. Multiple linear regression models were generated to predict the 6MWT distance.

Results:
A model predicting 6MWT was generated: systolic PAP, RVEF and age (r= 0.41, with PAP and RVEF
not
attaining significance). A second model entering IMP
LV
and age attained significance (r = 0.68, p<0.01). Fig 1.

Conclusions:
This is the first demonstration of the utility of the 6MWT distance to reflect a uniform measure of the status of the PH patient, less so PAP, even at baseline. The impedance between the LV and the aorta incorporates the dual components of RV
and
the LV integrated ventricular/arterial function along with the systolic PAP, making it a more fundamental measure of PHTN health status. Thus, despite >50 years of 6MWT used as the cornerstone for PHTN/PAH patients, we now show that this common application is really a predictor of impedance, and in turn, 6MWT was the right test for the wrong reason.
Abstract 9615: Predictors of Impedance During Subcutaneous ICD Defibrillation Testing in Hypertrophic Cardiomyopathy
Authors: Narayanan Chockalingam A , Shrestha Srijan , Gionfriddo William , Koethe Benjamin , Katcher Benjamin , Garlitski Ann , Weinstock Jonathan , Homoud Munther , Maron Barry , Maron Martin S , Rowin Ethan J , Madias Christopher
Published: April 2022

Introduction:
Defibrillation threshold testing (DFT) is generally reserved for populations with perceived concern for defibrillation failure, including in hypertrophic cardiomyopathy (HCM). Higher shock impedance has been associated with risk of DFT failure with subcutaneous defibrillators (SICD). The PRAETORIAN score is a chest radiograph based tool that evaluates device positioning to predict risk of DFT failure.

Objective:
We assessed predictors of impedance during DFT in a single center HCM SICD cohort.

Methods:
Data was collected from HCM patients who underwent SICD implantation from 2013 to 2021. Predictors of impedance were evaluated with linear and logistic regression.

Results:
Impedance was reported in 75 HCM SICD patients during DFT with 65J. DFT was successful in 74 patients with mean impedance of 72.7 ohm and septal thickness of 20.6 mm. Ten patients had massive HCM (> 30 mm) with mean impedance of 66.4 ohm. Septal thickness was not predictive of impedance (β 0.37, 95% CI 1.24-0.50; P = .40). Independent predictors of impedance were BMI (β 1.41, 95% CI 0.61-2.21; P = .0008) and PRAETORIAN score (β 0.14, 95% CI 0.05-0.22; P = .0015). Multivariable regression revealed BMI no longer significant and PRAETORIAN score remaining significant (β 0.10, 95% CI 0.01-1.66; P = .038).

Conclusion:
In this HCM SICD cohort BMI and PRAETORIAN score were predictive of impedance. However, in a multivariable model, BMI was no longer predictive, highlighting importance of implant technique to improve impedance and DFT. Additionally, patients with massive hypertrophy all had successful DFT and septal thickness was not predictive of impedance. HCM has historically been portrayed as a high DFT population. Further prospective trials are necessary to establish whether standard DFT practice can be applied in HCM.
Abstract 9672: Antiplatelet Therapy and Covid-19 Outcomes in Patients With Stable Coronary Artery Disease
Authors: Adelsheimer Andrew , Choi Justin , Evans Arthur
Published: April 2022

Introduction:
Severe COVID-19 can cause acute respiratory distress syndrome (ARDS), with pulmonary pathology composed of platelet microthrombi. Antiplatelet agents have been investigated as a treatment in ARDS, but without clear evidence of benefit. The decision on antiplatelet use in patients with COVID-19 and coronary artery disease (CAD) is key.

Hypothesis:
We assessed the hypothesis that increased use of antiplatelet therapy was associated with no worse clinical outcomes in COVID-19 among adults with stable CAD.

Methods:
We performed a retrospective cohort study of patients who presented with COVID-19 to two New York City hospitals from March 3 to May 15, 2020. Patients were separated into groups based on antiplatelet use, including no outpatient antiplatelet use, monotherapy, and dual antiplatelet therapy (DAPT). Outcomes and complications were compared among the groups, using propensity scoring with inverse probability of treatment weighting.

Results:
This study included 315 patients with stable CAD and COVID-19. Patients on no outpatient antiplatelet therapy were significantly older and more likely to be taking anticoagulation, while patients on DAPT had the highest rates of diabetes and chronic kidney disease. The most prescribed antiplatelet in the cohort was aspirin (72.1%) followed by clopidogrel (22.5%). There was no difference in COVID-19 admission mortality between the DAPT and monotherapy groups (DAPT 27.9%, monotherapy 27.2%, p=NS). Patients on DAPT had decreased rates of venous thromboembolism compared to monotherapy (DAPT 0.0%, monotherapy 6.4%, p=0.01), and bleeding rates were similar. The rate of home monotherapy continuation in hospital was 79.9%, with the most common reasons for discontinuation being hemorrhage, anemia, and thrombocytopenia. No outpatient antiplatelet use was a high-risk group, with the highest rates of intensive care admissions, intubations and mortality.

Conclusions:
In conclusion, we found no difference in COVID-19 outcomes for CAD patients on DAPT compared to those on monotherapy. There were decreased clotting complications in patients on more antiplatelet therapy, while bleeding rates were similar. No outpatient antiplatelet use was found to be a high-risk group in COVID-19.