bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11338: On-Clopidogrel Platelet Reactivity in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention and Association with Patient Characteristics
Authors: Gjermeni Diona , Vetter Hannah , Szabo Sofia , Anfang Viktoria , Hesselbarth David , Leggewie Stefan , Trenk Dietmar , Duerschmied Daniel , Bode Christoph , Olivier Christoph
Published: March 2022

Introduction:
On-clopidogrel platelet reactivity (PR) is associated with thrombotic and bleeding risk in patients undergoing percutaneous coronary intervention (PCI). Patient-related factors affect the level of PR. Patients with atrial fibrillation (AF) undergoing PCI are treated concomitantly with oral anticoagulants (OAC) potentially interacting with platelet function. This study aimed to investigate the association of PR with demographic and clinical characteristics in these patients.

Methods:
In this single-centre prospective observational cohort study, patients with AF with an indication for OAC were enrolled during hospitalization after PCI with clopidogrel. TRAP- and ADP- induced PR (TRAP 32 μM, ADP 6.4 μM) were assessed by multiple electrode aggregometry. ADP-induced PR was normalized to TRAP-induced PR (r-ADP-agg).

Results:
159 patients were enrolled between May 2020 and May 2021. The median age was 78 years (interquartile range, IQR 72-82), 112 (70%) were male and 39 (25%) presented with ACS. 68 (43%) presented with chronic kidney disease (CKD), defined as GFR<60. 54 (34%) patients received apixaban, 6 (4%) dabigatran, 18 (11%) edoxaban, 74 (47%) rivaroxaban and 4 (3%) marcumar. 128 (81%) patients received clopidogrel loading. Median ADP-induced PR was 12 U (IQR 6-17); median r-ADP-agg was 24% (IQR 14-39). ADP-induced PA is significantly correlated with age (r=-0.22; p=0.035) and platelet count (r=0.22; p=0.006). Compared to the patients without CKD,patients with CKD had a significantly lower ADP-induced PA (median 8 [IQR 10] vs. median 13 [IQR 10]; p<0.001) and r-ADP-agg. (median 20 [IQR 25] vs median 28 [IQR 24]; p=0.003).In a multivariable linear regression, ADP-induced PR was significantly associated with age (r=-0.177, CI:-0.481 to -0.018, p=0.035), immature platelet count (r=0.178, CI: 0.003 to 0.729, p=0.048), and diabetes mellitus (r=0.21, CI: 1.192 to 9.087, p=0.011). CKD was associated with both: lower ADP-PR (r=-0.262, CI:-9.962 to -2.396, p=-0.002) and lower r-ADP-agg (r=-0.253, CI:-9.962 to -2.396, p=0.003).

Conclusions:
In this patient cohort the association of on-clopidogrel PR as assessed by multiple electrode aggregometry with patient related factors was weak and most pronounced for chronic kidney disease.
Abstract 11346: Overcoming Barriers to Complete and Early Extraction for CIED Infection: A Narrative Review of the Epidemiological, Clinical and Economic Evidence
Authors: Sood Ami
Published: March 2022

Background:
As the number of patients with cardiac implantable electronic devices (CIEDs) grows, they are likely to present with issues to diverse groups of physicians. Clinical guidelines have Class I recommendations for complete CIED extraction for infection. Guideline-adherent management is associated with improved prognosis in patients with CIED infection. However, this is insufficiently implemented in practice and there is limited discussion on barriers and solutions to optimizing treatment.

Purpose:
The objective is to provide a comprehensive overview of CIED infections with respect to (1) current guidelines for treatment of CIED infection (2) awareness of those guidelines in clinical practice, and (3) overcoming barriers to the guideline adherence.

Methods:
This review assessed the current literature landscape from January 1, 2005 to October 21, 2020 on the burden of CIED infection, clinical outcomes for CIED extraction, and guideline recommendations pertaining to CIED extraction.

Results:
Fifty-seven publications were included for this review. Five clinical practice guidelines reported a Class I indication for complete device and lead removal in all patients with defined CIED infection (systemic, local, bacteremia, or infection endocarditis). CIED infection rates ranged between 0.8% to 4.2% globally and such infections were found to be associated with substantial clinical and economic burden. Clinical studies assessing CIED extraction for infection consistently reported high procedural success (~95%), low major procedural complication rates (0% to 4.8%) and very low procedural mortality rates (0% to 2.4%). Furthermore, several studies reported that complete and early extraction has significant clinical and economic benefit compared with no extraction or late extraction. However, a large physician survey reported poor compliance with recommendations globally.

Conclusions:
The research indicates that barriers to optimal treatment may include challenges with infection diagnosis and patient referral to extraction centers, as well as misconceptions regarding extraction procedures. To help address these barriers, a multiprong quality initiative to optimize patient care pathways and increase awareness is necessary.
Abstract 11365: Electronic Cigarette Vaping with or Without Heating Induces Differential Pathological Remodeling in the Lungs and Right Heart
Authors: Estifanos Yohannes , Peterson Matthew R , Rice Tatiana , He Guanglong
Published: March 2022

Introduction:
One of the obstacles in dissecting the specific underlying mechanisms of electronic cigarette (EC) “vaping”-related health effects is the complexity in the chemical composition of EC aerosols. As various chemicals are generated through the heating coil in addition to the intact components presented in the aerosol, we hypothesize that the heating-associated by-products and the intact components would have differential pathological impact to the remodeling of right ventricular (RV) and pulmonary system.

Methods:
Using a prototype exposure system, C57BL/6 mice were exposed to room air or EC vapor with and without heating the EC liquid (ECL) for 3 hours per day, 5 days per week for 6 months. Echocardiography with color Doppler was used to evaluate cardiac structure and function. To assess inflammatory and fibrotic signaling, Western-blotting was performed.

Results:
Comparable plasma cotinine levels were found between heating and non-heating exposure, respectively (59.34±8.57ng/mL vs 59.02± 4.83ng/mL; n=5-7). Without heating exposure caused thinning of RV free wall (0.57±0.028 mm control vs 0.43±0.03 mm exposed; p<0.05), whereas with heating, an increase in the RV wall thickness (0.79±0.06 mm exposed, p<0.01) and a reduction in RV chamber size at diastole (1.57±0.04mm control vs 1.34±0.03mm exposed, p<0.01) were observed. While exposure without heating elevates peak pulmonary artery (PA) pressure (2.46±0.31 mmHg control vs 3.34±0.13 mmHg exposed; p<0.05), a lower peak (1.36± 0.12 mmHg exposed; p<0.05) and mean pressure gradient (0.75±0.08 mmHg control vs 0.51± 0.05 mmHg exposed; p<0.05) were recorded with heating exposure. As for pulmonary response, exposure without heating did not affect NF-κB p-p65 level, but reduced p65 expression to 37% of controls (±6%, n=5, p<0.0001) and increased TGF-β1 by 67% (±11%, n=5, p<0.05). In contrast, exposure with heated ECL did not affect p65 and TGF-β1 but increased p-p65/p65 by 39.4% (±5%, n = 5, p < 0.05), indicating activation of NF-κB inflammatory signaling.

Conclusions:
EC exposure without heating the ECL resulted in fibrotic lung, higher peak PA pressure and RV dystrophy without obvious pulmonary inflammation. Heating the ECL, however, contribute to RV hypertrophy and pulmonary inflammation.
Abstract 11367: Chronic Kidney Disease and 6-12 Month Outcomes After Transcatheter Aortic Valve Replacement
Authors: Twing Aamir , Dickens Helena , Marrero-Rivera Gabriel , Gokhale Sanket , Jarsania Dhairya , Slostad Brody D , Kansal Mayank M , Groves Elliott , Shroff Adhir R
Published: March 2022

Introduction:
Chronic kidney disease (CKD) is known to accelerate the progression of aortic stenosis (AS) and portends adverse outcomes in patients treated with surgical valve replacement. Long-term outcomes in CKD patients after transcatheter aortic valve replacement (TAVR) have been less studied. The purpose of this study is to examine outcomes after TAVR in CKD patients as stratified by glomerular filtration rate (GFR).

Hypothesis:
CKD is associated with poorer outcomes after TAVR.

Methods:
Retrospective electronic medical record review from March 2018-June 2020 at the University of Illinois, Chicago and Jesse Brown Veteran’s Administration Medical Center (Chicago, Illinois) identified TAVR patients, who were included if they followed-up within 6 and 12 months of procedure. Patients were stratified into 4 classes by baseline GFR (mL/min): >90, 60-89, 30-59, <30 with the latter 3 groups comprising CKD patients. Outcomes were expressed as event rates and included 6 and 12-month MACE (all-cause mortality, MI, or CVA) and 30-day rehospitalization. Chi-square analysis was used to compare differences across GFR groups.

Results:
118 patients (age 76±10 years, 79% male, 46% white) followed up at 6-months and 112 did so at 12-months. There were no statistically significant differences in baseline demographics or comorbidities between CKD and non-CKD patients. CKD patients were more likely to experience MACE compared to non-CKD patients at 6 (p=0.04) and 12-months (p=0.009, Fig. 1). CKD patients also had a higher rate of 30-day rehospitalization (p=0.003).

Conclusion:
Our results demonstrate that CKD portends adverse outcomes after TAVR with CKD patients experiencing an increased risk of 6 + 12-month MACE and 30-day re-hospitalization. Decreasing GFR correlated with higher rates of MACE at 6 and 12 months.
Abstract 11369: Leveraging an Artificial Intelligence-Enabled Ecg Algorithm for Atrial Fibrillation Detection to Predict Long-Term Ischemic Stroke and Cardiovascular Mortality in the Community
Authors: Medina-inojosa Jose R , Attia Zachi , Noseworthy Peter A , Siontis Konstantinos , Baez Abraham , Shelly Michal , Friedman Paul , Lopez-jimenez Francisco
Published: March 2022

Background:
Artificial intelligence (AI)-based analysis of the electrocardiogram (ECG) can estimate the probability of having atrial fibrillation (AF) while in sinus rhythm. We evaluated the association between the probability of AF using AI-ECG and incident ischemic stroke (I-Stroke) and cardiovascular (CV) mortality.

Methods:
We evaluated a community-based cohort of consecutive patients that sought primary care in Olmsted County, MN, from the years 1998 to 2000 followed-up through March 2016. Inclusion criteria were ages 40-79, an electrocardiogram within 2 years and complete CHA2DS2-VASc data. We excluded those with known atherosclerotic CV disease or AF. The AI network was developed in 180,000 patients (649,931 ECG). The primary endpoint was incident I-Stroke; secondary endpoint was I-Stroke or CV mortality; validated in duplicate. Multivariate cox models adjusted for age, sex, history of hypertension, diabetes, heart failure, and in CHA2DS2-VASc Score subgroups (categorized as low=0, moderate=1, and high risk ≥2).

Results:
We included 14,601 patients, mean age 53.2±13.08 (51% women, 95% whites), CHA2DS2-VASc score 1.3±1.2, median follow-up of 16.3 years, IQR 14.5-17.5, 727 (4.9%) had an I-Stroke and 1309 (8.9%) had I-Stroke or died from CV causes. When comparing the 5
th
vs the 1
st
quintile, those with high AI-ECG AF probability had increased risk for I-Stroke (HR 3.25, 95%CI 2.55-4.14, P-for trend <.0001
Figure-A
) and ischemic stroke or CV mortality (HR 5.73, 95%CI 4.69-6.99, P-for trend <.0001
Figure-B
). This remained significant after adjustments. Furthermore, AI-ECG AF probability was associated with I-Stroke across CHA2DS2-VASc risk levels (HR 2.43 for high, 2.33 for moderate, 1.98 for low CHA2DS2-VASc risk, all P<0.01).

Conclusion:
The AI-ECG AF algorithm predicts long-term I-Stroke and CV mortality and may refine CHA2DS2-VASc. These results highlight the utility of the AI enabled ECG when estimating I-Stroke or CV mortality risk.
Abstract 11378: Reference Intervals of Activated Clotting Time in Pediatric Patients Undergoing Cardiac Surgery
Authors: Maiga Arhamatoulaye , Tremblay Julie , Lamoureux-Asselin Benoit , Nyalendo Carine , Toledano Baruch , Poirier Nancy C , Rivard Georges-Étienne , Bonnefoy Arnaud
Published: March 2022

Introduction:
Monitoring the anticoagulant effect of heparin is critical to prevent thrombosis and/or bleeding during cardiac surgery. This evaluation is usually performed by assessing the activated clotting time (ACT) with a POC device. Despite the relevance and widespread use of ACT, there are currently limited reference values to use as a target. Furthermore, compared to the adult population, infants have been described with a longer ACT, reinforcing the need to establish a separate reference interval for this segment of the population.

Aim:
The present work aims to propose reference intervals of ACT in pediatric patients.

Methods:
We collected data on 155 consecutive patients, ranging in age from 1 day to 18 years, undergoing cardiac surgery from 01-2019 to 01-2021 at Sainte-Justine hospital. Prior to surgery, patients were given UFH as a bolus of 3 mg/kg, and Hemochron Signature Elite ACT+ (Accriva Diagnostics, Inc.) was used to measure ACT before and promptly after heparin injection. Data were subsequently analyzed by using a parametric method. Lower and upper reference limits are the values at the 2.5 and 97.5 percentile, respectively.

Results:
The ACT before heparin injection followed a normal distribution with a lower reference limit at 85 seconds and an upper limit at 147 seconds compared to the range of 70-120 seconds proposed for the general population. Interestingly, the ACT after heparin bolus exhibited a non-gaussian distribution. Since neonates have been previously described with a greater heparin resistance compared to older infants; patients were separated into two age groups: patients < 1-month of age (Group A; n=31) and patients > 1-month (group B; n=124). Afterward, we performed a log transformation of the ACT values after heparin injection to approximate a Gaussian distribution, yielding mean ACT value of 392 seconds (limits 291-529 seconds) for Group A and 473 seconds (limits 314-996 seconds) for Group B (Welch test p value = 4.4 10
-6
). No significant difference in ACT values prior to heparin bolus was found between the two groups.

Conclusion:
Overall, our results provide reference values of ACT measured using an Hemochron device, in a pediatric context, paving the way for improved patient care during cardiac surgery.
Abstract 11380: Undersizing Mitral Annuloplasty Acutely Eliminates Functional Mitral Regurgitation but Does Not Relieve Tethering Forces on the Mitral Valve Chordae Tendineae
Authors: Xu Dongyang , Zhan-Moodie Samantha , Sreerangathama Suresh Kirthana , He Qi , Padala Muralidhar
Published: March 2022

Introduction:
Functional mitral regurgitation (FMR) develops secondary to mitral valve (MV) geometric distortions such as isolated annular dilatation (AD), asymmetric tethering (Asym), and symmetric tethering (Sym). Undersizing mitral annuloplasty (UMA) has been religiously used to repair FMR with the notion that it can restore coaptation and relieve tethering forces, which has not been tested.

Hypothesis:
UMA does not relieve MV chordal tension in the setting of FMR from AD, Asym and Sym despite correcting regurgitation.

Methods:
In an ex vivo MV simulator (
Fig. A
), fresh pig MVs were mounted onto an adjustable annulus and two papillary muscle displacing rods (
Fig. B
), which are used to induce AD, Asym and Sym MV configurations. A 28mm annuloplasty ring was implanted (
Fig. C
) after the three MV geometries were established. MV hemodynamics were measured using electromagnetic flowmeters, leaflet kinematics were measured by 2D echocardiography, and chordal forces were measured using miniature C-ring force transducers.

Results:
Regurgitation fraction was significantly reduced in the Asym and Sym geometries after 28mm annuloplasty (Asym: 5.3±3.7% vs 1.6±1.2%, p=0.024; Sym: 12.8±5.6% vs 5.6±3.1%, p=0.006) (
Fig. D
). Tenting height was not significantly reduced after annuloplasty in all valve geometries, indicating persistent tethering despite annular downsizing (
Fig. E
). Neither anterior nor posterior leaflet mobility was improved after annuloplasty (
Fig. F-G
). The chordal forces in the anterior strut and posterior strut chordae tendineae were depicted in (
Fig. H1-4
). The peak forces in the chordae slightly reduced after UMA, but the reduction in the peak forces did not reach statistical significance.

Conclusions:
UMA corrects FMR by forcing the leaflets together in the mitral valve orifice but does not improve leaflet mobility or relieve the tethering forces on the leaflets, which explains the mechanistic basis for high rates of recurrent FMR after UMA.
Abstract 11382: Left and Right Ventricular Strain Mechanics in Fetal Arrhythmia
Authors: Haligheri Geetha , Chellu Neha , Komarlu Rukmini R
Published: March 2022

Introduction:
Assessment of ventricular mechanics in fetuses with tachyarrhythmia poses significant challenges. Strain analysis measures myocardial deformation and has been shown to be a very sensitive marker of ventricular systolic dysfunction compared to traditional measurements. Global and regional myocardial deformation has not been well described in fetuses with arrhythmias.

Hypothesis:
We hypothesize that left and right ventricular myocardial mechanics are impaired in fetuses with tachyarrhythmias compared to normal fetuses in sinus rhythm.

Methods:
Retrospective review of fetuses with tachyarrhythmia (groups 1 and 2) and gestational age (GA) matched normal fetuses with normal cardiac anatomy (group 3) from 2000 to 2018 at a single institution, with IRB approval. Fetuses with isolated ectopy and congenital heart disease were excluded from all groups. Strain analysis was performed using VVI software. Arrhythmia type, medications, cardiovascular profile score and postnatal outcome were collected.

Results:
18 fetuses with tachyarrhythmia with GA between 21 to 36.5 weeks were analyzed; 18 fetuses of similar GA with normal cardiac anatomy in sinus rhythm served as controls. 3 fetuses were delivered close to term and did not have strain assessment in sinus rhythm. Both LV global longitudinal strain (-4.44 ± 2.82%) and strain rate (-1.24 ± 0.85%) and RV global longitudinal strain (-6.76 ± 2.09%) and strain rate (-1.41 ± 0.55%) were reduced in tachyarrhythmia (Group 1) and recovered when in sinus rhythm (Group 2) but still reduced compared to controls (Group 3). Global longitudinal velocity was not different between patients in Group 2 and 3 (Table & Fig 1).

Conclusions:
Strain parameters remain abnormal in fetuses with tachyarrhythmia despite conversion to sinus rhythm when compared to GA matched controls. Serial evaluation of strain will help guide therapy and monitor ventricular function in this patient population.
Abstract 11383: Automated Measurement of Global Longitudinal Strain by Speckle-Tracking Echocardiography in Cardio-Oncology Patients Using Artificial Intelligence
Authors: Hanif Waqas , Goldberg Ythan , Taub Cynthia C , Vorchheimer David A , Slipczuk Leandro , Ho Edwin , Rodriguez Carlos , Farooq Muhammad , Garcia Mario J , Zhang Lili
Published: March 2022

Introduction:
Left ventricular (LV) global longitudinal strain (GLS) is a robust LV systolic function measure used to detect subtle chemotherapy cardiotoxicity. However, inter-reader and inter-vendor variabilities compromise the clinical value of longitudinal follow-up of GLS. Artificial intelligence (AI)-based, fully automated measurement of longitudinal strain may be more reliable compared with human interpretation.

Methods:
We studied 52 transthoracic echocardiographic examinations randomly selected from a Cardio-oncology registry. All subjects received anthracycline-based chemotherapy in 2016-2019. AI-based longitudinal strain was assessed by EchoGo Core using standard 2- and 4-chamber apical views. Two readers verified the myocardium tracing by AI and found no errors. Longitudinal strain results by EchoGo were compared to GLS measured by conventional software (TomTec and Philips QLAB) using standard 3-, 2- and 4-chamber apical views.

Results:
AI-based longitudinal strain analysis was feasible in 51/52 (98%) transthoracic echocardiographic studies. The mean longitudinal strain was -17.3±3.3% for EchoGo, -16.9±2.4% for TomTec and -17.5±3.1% for QLAB. Bland-Altman analysis showed a bias of -0.4 ± 2.7% and 95% limits of -5.7 to 4.9% between EchoGo longitudinal strain and TomTec GLS (Figure 1A). A bias of 0.2 ± 3.3% and 95% limits of -6.2 to 6.6% between EchoGo longitudinal strain and QLAB GLS (Figure 1B) were seen. The bias between TomTec GLS and QLAB GLS was 0.6 ±2.2% (Figure 1C). The inter-reader correlation coefficients of TomTec GLS and QLAB GLS were 0.57 and 0.71, respectively.

Conclusions:
This novel AI-based longitudinal strain analysis was feasible in the majority of echocardiograms without any operator input. The bias between EchoGo longitudinal strain and conventional software appears small. AI-based myocardial strain analysis may reduce variabilities and facilitate longitudinal follow-up of GLS in Cardio-oncology patients.
Abstract 11384: Discharge and De-Escalation After VAD Implant in Children with Dilated Cardiomyopathy: A Multi-Center Quality Improvement Initiative
Authors: Butto Arene , Connelly Chloe , Bearl David , Lorts Angela , O'Connor Matthew J , Rosenthal David N , Tunuguntla Hari , Conway Jennifer
Published: March 2022

Introduction:
Children with dilated cardiomyopathy (DCM) are increasingly bridged to heart transplant (Tx) with intracorporeal continuous flow ventricular assist devices (VADs), but there continues to be variability in hospital discharge. We sought to assess the impact of a quality improvement (QI) project promoting hospital discharge in pediatric VAD patients with DCM.

Methods:
Patients enrolled at sites participating in the Discharge and De-Escalation QI project of the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry were eligible. Patients with a HeartWare (HVAD) or HeartMate3 (HM3) VAD, implanted between April 2018 and February 2021, were included. Patient characteristics and outcomes were compared before and after the QI initiative, which targeted team and family expectations, was implemented in November 2019.

Results:
There were 85 patients (75%) with DCM and/or myocarditis who were included in this study (median age 14 years; median weight 57.1 kg; 67% male). Among 57 patients in the baseline group, 56% (n=32) were discharged with a mean post-implant hospital length of stay (LOS) of 36 days and 44% (n=25) underwent Tx during index VAD admission, with a mean of 52 days on device. There were 28 patients in the intervention group; 64% (n=18) were discharged with a mean LOS of 45 days, while 29% (n=8) patients underwent Tx during index VAD admission, with a mean of 44 hospital days on device. There was no significant difference in the frequency of hospital discharge or in hospital LOS between groups.

Conclusions:
Pediatric centers discharged just over half of DCM patients supported on an HVAD or HM3, with nearly one third of patients undergoing transplant during the index VAD admission. The QI intervention did not significantly alter the discharge rate. Further work is required to understand practice variation between centers with respect to Tx listing and organ acceptance for children on intracorporeal continuous flow VADs.
Abstract 11393: Lipidomics Profiling and Risk for Cardiovascular Disease: A Longitudinal Study in American Indians
Authors: Zeng Wenjie , Miao Guanhong , Chen Mingjing , Zhang Ying , Umans Jason G , Cole Shelley A , Lee Elisa T , Howard Barbara , Fiehn Oliver , Zhao Jinying
Published: March 2022

Background:
Dyslipidemia is an established risk factor for CVD. Standard lipid panel lacks description of the full spectrum of blood lipids. A longitudinal profiling of blood lipidome in relation to the risk of CVD is lacking in any racial/ethnic groups.

Objective:
Identify novel lipid species associated with risk of CVD in American Indians, independent of traditional risk factors (TRFs).

Method:
Using untargeted LC-MS, we repeatedly measured 1,542 lipid species in 3,916 fasting plasma samples from 1,958 participants who attended two exams (~5.5 years apart) and were followed up to 18 years in the Strong Heart Study. Elastic net was used to select baseline lipids and change in lipids (baseline to 5-year follow-up) associated with 18-year risk of CVD. Multivariate and network analyses were conducted to identify discriminatory lipidomic signatures and differential lipid networks associated with risk of CVD.

Results:
Of 1,911 participants free of CVD at both baseline (2001-2003) and 5-year follow-up (2006-2009), 222 developed CVD after 18 years of follow-up. High-resolution LC-MS detected 1,542 lipid species (518 known). After adjusting for TRFs (age, sex, center, smoking, BMI, hypertension, diabetes, LDL-c, and albuminuria), elevated baseline levels of 21 known lipids, including cholesterol esters, sphingolipids, glycerophospholipids, and fatty acids, were significantly associated with increased (HR: 1.08 to 1.26) or decreased (HR: 0.81 to 0.91) risk of CVD. Longitudinal change in 13 lipids, including cholesterol esters, sphingolipids, glycerophospholipids, and fatty acids, were either positively (HR: 1.03 to 1.28) or inversely (HR: 0.75 to 0.92) associated with risk of CVD at 18-year follow-up. A

lipid score comprising 10 baseline lipids significantly improved risk prediction beyond TRFs (ROC increases from 0.823 to 0.837, P = 0.009). Multivariate and network analyses identified distinct lipidomic signatures and lipid networks associated with risk of CVD.

Conclusion:
Novel molecular lipids significantly predict risk of CVD beyond TRFs in American Indians. Our findings provide novel lipid molecules for risk stratification and shed light on the mechanism linking lipid dysregulation to CVD in American Indians.
Abstract 11395: Randomized Feasibility Study of Problem-Solving Therapy Compared to Stroke Education for Depressive Symptoms and Quality of Life in Stroke Survivor-Care Partner Dyads
Authors: Tierney Meghan , Hadidi Niloufar N
Published: March 2022

Introduction:
Stroke survivors often face multiple physical and/or cognitive disabilities requiring ongoing assistance with activities of daily living. Family members often step in to provide this care. Both stroke survivors and care partners commonly report depressive symptoms impacting health and QOL. Poststroke depression is well-studied in survivors, but care partner depression is less understood. Symptoms shared by stroke survivors and their care partners present opportunities for dyad-focused interventions. Problem-Solving Therapy (PST) is a psychosocial intervention that has been effective for managing depression. We adapted this therapy in a novel way for use with stroke survivor-care partner dyads for reduction of depressive symptoms and improvement in QOL. Our primary aim was to address the feasibility and acceptability of PST with secondary aims measuring changes in PHQ-9 and EQ-5D pre/post intervention.

Methods:
A convenience sample of 14 adult stroke survivor-care partner dyads were randomized 1:1 to either 6 weekly sessions of PST or 6 matched weekly sessions of stroke-related health education as an attention control group. Participants completed PHQ-9 and EQ-5D at baseline, mid-point, and post-intervention. Survivor functional status and caregiver burden were also assessed at these points.

Results:
The PST intervention was well-received by dyads with 100% of post-intervention ratings indicating satisfaction or great satisfaction with the experience. Participants reported being challenged to think differently (55.6%), improved dyad communication (44.4%) and feeling a sense of accomplishment (33.3%). Analysis focused on feasibility measures, identifying recruitment challenges and design considerations for subsequent studies. No significant changes in outcome measures were noted in this small sample.

Conclusion:
A dyad approach to behavioral interventions may promote a sense of well-being by providing an opportunity to address challenges that are faced by both individuals. Feasibility and acceptability were established in this small sample; future studies should focus on a larger, diverse sample. Participant feedback suggests booster sessions may also be helpful in sustaining the impact of this novel approach.
Abstract 11397: Impact of Von Willebrand Factor Multimer Abnormalities on Blood Loss After Aortic Valve Replacement Using the Semi-Automated Hydragel 5 Multimer Assay
Authors: Hamiko Marwan , Gerdes Lena , Seidel Holger , Westhoven Philipp , Kruppenbacher Johannes , Hertfelder Hans-Jörg , Kohistani Zaki , Duerr Georg Daniel
Published: March 2022

Introduction:
Acquired von Willebrand syndrome (aVWS) is common in patients with severe aortic stenosis (sAS), which is characterized by the loss of high-molecular-weight multimers (HMWM) of the von Willebrand factor (VWF). VWF abnormalities are improved after surgical aortic valve replacement (SAVR). While conventional multimer analysis is technically challenging, lengthy and non-standardized, recently a new semi-automated multimer assay, the Hydragel 5 VWF multimers (H5VWM) has become available. Therefore, the aim of our study was to analyze VWF abnormalities by H5VWM in patients undergoing SAVR in terms of echocardiography parameter and perioperative bleeding.

Methods:
We prospectively included 52 patients (age: 67.9±7.2 years; 53.8% male) undergoing SAVR. Patients were divided in two groups (A: abnormal VWF, n=24; B: normal VWF, n=28). Blood samples and echocardiographic data were collected at three time points (TP): day before SAVR (TP1), 7 days (TP2), and 3 months (TP3) after SAVR. Blood loss from chest drainage and the use of blood and haemostatic products were evaluated peri- and postoperatively.

Results:
Baseline characteristics were similar in both groups. Loss of HMWM was present in 38.5%. After SAVR the level of HMWM had increased significantly compared to baseline in group A. At TP3, we observed no loss of HMWM at all. Bleeding occurred in 15% (A: 17% vs. B: 14%; p>0.999) with need of re-thoracotomy in about 10% (A: 8% vs. B: 11%; p>0.999). There was no significant difference in postoperative bleeding in the first 24hrs (A: 491 ml vs. B: 701ml; p=0.255). Also, peri- and postoperative need of blood transfusion and haemostatic agents were similar between both groups. HMWM was inversely correlated with the peak aortic gradient (R=-0.557; p<0.001) and positively correlated with the aortic valve area (R=0.292; p=0.04).

Conclusion:
Loss of HMWM was not associated with increased postoperative bleeding in patients with sAS. Echocardiographic parameters could predict the loss of HMWM. The complete restoration of altered VWF at three months postoperatively, demonstrated by H5VWM, seems to be indicative for successful SVAR. Therefore, H5VWM, as a rapid and sensitive assay, could be included as diagnostic tool of suspected aVWS in AS patients.
Abstract 11402: Targeting RyR2 to Suppress Ventricular Arrhythmias and Improve Left Ventricular Function in Chronic Ischemic Heart Disease
Authors: Schmeckpeper Jeffrey , Kim Kyungsoo , Blackwell Daniel J , Woodall Kaylen , Knollmann Bjorn C
Published: March 2022

Introduction:
Sarcoplasmic reticulum Ca
+2
leak from RyR2 is a common finding in chronic ischemic heart disease (CIHD) and may be a key driver for ventricular arrhythmias and reduced excitation-contraction coupling in failingm myocytes. Here, we test the hypothesis that targeting Ca
+2
leak using the non-selective RyR inhibitor, Dantrolene, suppresses ventricular arrhythmias and improves left ventricular contractile function in CIDH.

Methods:
CHID was induced in 24 C57BL/6J mice by left coronary artery ligation. Four weeks after myocardial infarction (MI), subcutaneous osmotic pumps were placed to deliver continuous dantrolene (20 mg/kg/day) or vehicle (0.9% Saline). Left ventricular (LV) function was assessed by echocardiogram at 4-, 7- and 10-weeks post-MI. Peripheral muscle strength was assessed by provoked electromyogram at 6 weeks. Inducibility of ventricular tachycardia (VT) was assessed by rapid transesophageal pacing with isoproterenol at 10 weeks.

Results:
Dantrolene reduced the peripheral muscle strength in mice (0.014±0.001 vs 0.010±0.001 N, P<0.05), but had no adverse effects on weight loss or mortality. Dantrolene increased fractional shortening (18.7±1.3% vs 22.1±1.6%, P<0.001) and mean velocity fiber shortening (mVcfc 1.37±0.09 vs 1.74±0.1 circ/sec, P<0.002) in non-infarcted regions at 10 weeks. This prevented the progression in LV ejection fraction reduction from 4 to 10 weeks (Saline: 35.6±3.4% to 30.6%±3.4%; Dantrolene 34.6±2.4% to 38.1±1.9% vs, P<0.01). Dantrolene reduced VT frequency per animal (0.083±0.04 vs 0.028±0.02 VT/pacing train, P<0.02) and the total duration of inducible VT per animal (59.2±24 secs vs 1.2±0.6 sec, P<0.04). Dantrolene significantly prolonged the ventricular effective refractory period (VERP) (35.1±1.6 msec vs 42.0±0.9 msec, P<0.005).

Conclusion:
Dantrolene suppression of RyR2 diastolic Ca
+2
leak in chronic ischemic heart failure improves the systolic function of surviving myocardium and reduces VT burden by prolonging the VERP, preventing the re-entry circuit for VT in this model. RyR2 inhibition may represent a new therapeutic target for the treatment of CIDH with ventricular arrhythmias.
Abstract 11407: E-Cigarettes Induce Dysregulation of Autophagy Leading to Endothelial Dysfunction in an Ipsc Model of Pulmonary Arterial Hypertension
Authors: Liu Chen-wei , Le Hoai , Denaro Philip , Ong Sang-Ging , Lee Won Hee
Published: March 2022

Introduction:
Given the increasing popularity of electronic-cigarettes (e-cigs), it is imperative to evaluate the potential health risks of e-cigs especially in users with pre-existing health concerns. Although we have recently demonstrated that acute exposure to e-cig exacerbates endothelial dysfunction, a prominent feature of pulmonary arterial hypertension (PAH), it is currently unknown whether the use of e-cig represents an even higher risk factor in PAH patients. The aim of the present study is to assess if differential susceptibility exists between healthy and PAH patients following e-cig exposure and mechanisms contributing to it.

Methods and Results:
Using patient-specific induced pluripotent stem cells (iPSCs) derived from both PAH patients and healthy controls, we showed that PAH iPSC-derived endothelial cells (iPSC-ECs) exhibited increased susceptibility against e-cig exposure compared to healthy iPSC-ECs leading to significantly decreased cell viability, increased reactive oxygen species generation and apoptosis, and reduced tube formation and migration. Transcriptomic analyses revealed that differential expression of AKT3 may be responsible for triggering enhanced autophagic flux impairment in PAH iPSC-ECs compared to healthy iPSC-ECs which underlies increased susceptibility upon e-cig exposure. Consistent with sequencing data, western blot confirmed that AKT3 level was decreased in PAH iPSC-ECs following e-cig exposure and AKT3 proteasomal degradation was mediated by K48-linked ubiquitination. Moreover, knockdown of AKT3 in healthy iPSC-ECs significantly induced autophagic flux impairment and increased endothelial dysfunction and these vascular toxicities were further increased when exposed to e-cig, thus mimicking the PAH cell phenotype after e-cig exposure. Finally, rapamycin treatment reversed e-cig-induced decreased AKT3 level, endothelial dysfunction, and autophagy impairment in PAH iPSC-ECs.

Conclusions:
Taken together, these data suggest a potential link between autophagy and Akt3-mediated increased susceptibility to e-cig in PAH.
Abstract 11414: Transplantation of Epididymal Adipose Tissue from Mice with Myeloid Deletion of RAGE Induces Insulin Resistance in Wild-Type Mice
Authors: Arivazhagan Lakshmi , Wilson Robin , Ruiz Henry , Ramasamy Ravichandran , Schmidt Ann Marie
Published: March 2022

Introduction:
Obesity is a major global health problem and often associated with insulin resistance (IR). Our previous work showed that global and adipose tissue specific
Ager
deletion provide protection from HFD induced weight gain and insulin resistance. We identified that myeloid-specific of
Ager
deletetion (MDR) further impairs insulin sensitivity in mice fed HFD without further increasing body weight vs. control animals. These effects of myeloid
Ager
deletion were reversed upon simultaneous deletion of adipocyte
Ager
in HFD feeding. In parallel, the expression of inflammatory genes was significantly higher in the epididymal adipose tissue (eWAT) of MDR vs. all other mice groups. We tested the hypothesis that eWAT-borne factors from mice bearing myeloid
Ager
deletion induce IR upon transplantation to wild-type mice fed low fat chow.

Methods:
We generated mice with myeloid-specific (MDR) LyzMCre(+/+).Ager

flox/flox

and adipocyte and myeloid-specific (Double Knockouts (KO)) AdipoQCre(-/+)LyzMCre(+/+).Ager

flox/flox

deletion of
Ager
and LysMCre mice (Cre control) were used as control. Mice were fed HFD (60% kcal/fat) for 3 months starting at age 6 weeks. Mice were assessed for body mass and glucose and insulin sensitivities. After 12 weeks of HFD feeding, eWAT from these HFD fed mice was transplanted into C57BL/6 (WT) mice. The transplanted recipient mice were maintained on a low fat diet and their body mass, blood glucose and insulin sensitivity were monitored.

Results:
6 weeks after eWAT transplantation into WT mice, only the WT low fat diet-fed recipients of MDR eWAT displayed IR in comparison to recipients of Cre control or Double KO eWAT. Despite no difference in the body weight, native eWAT adipocyte size was significantly higher in the recipients of MDR eWAT vs. all other groups. Differences in F4/80-positive crown like structures were also observed in native recipient eWAT, which might underlie mechanisms of IR.

Conclusion:
Transplantation of eWAT from mice devoid of myeloid
Ager
and previously fed HFD confers IR to low fat diet WT mice. The molecular mechanisms mediating these effects are under investigation.
Abstract 11415: Extent of Leaflet Coaptation Governs the Biomechanics of Mitral Valve Neochordae Used for Posterior Leaflet Prolapse
Authors: Xu Dongyang , Sreerangathama Suresh Kirthana , Nambiar Hirschel , He Qi , Padala Muralidhar
Published: March 2022

Introduction:
Reducing peak forces and stresses on the neochordae used to repair mitral valve prolapse, can inhibit their late failure, and increase repair durability. Restoring a larger shelf of leaflet coaptation at the time of repair, could reduce neochordae stresses and aid durability.

Hypothesis:
In this study, we hypothesized that using a slightly smaller annuloplasty ring can yield a higher systolic coaptation length, which in turn could reduce the neochordal forces/stresses.

Methods:
Pig MV (n=7) were excised and studied in a pulsatile left heart simulator (
Fig. A
), with P2 prolapse induced by transecting the marginal chordae (
Fig B1,2
). Repair was performed with force transducer instrumented Goretex PTFE suture loops (6-0) (
Figure C1,2
), and annuloplasty with a custom adjustable ring that could be reduced from 36mm to 30mm in 2mm increments (
Fig D1,2
). Regurgitant fraction, leaflet coaptation, and temporal neochordae force traces were measured.

Results:
P2 prolapse increased MR compared to baseline (10.5 ± 7.7% vs 0%, p=0.0001), which was reduced by neochordoplasty and annuloplasty (
Fig. E
). Leaflet coaptation length increased from 0mm to 11.3 ± 3.8mm with neochordae alone, and further increased with annuloplasty to 12.7 ± 3.6mm with 34mm, 14.8 ± 4.4mm with 32mm and 15.7 ± 3.9mm with 30mm (
Fig. F
). With increasing coaptation, the peak neochordae forces reduced (
Fig G, H
), demonstrating a negative correlation between parameters (
Fig I
).

Conclusions:
Neochordal forces can be reduced by increasing the coaptation length with slight downsizing of the mitral annulus. An operative strategy achieving larger coaptation can yield a biomechanically optimal repair configuration, potentially improving durability.
Abstract 11420: Platelet Activity Mediates Increased Cardiovascular Risk in Patients with End-Stage Kidney Disease and Peripheral Artery Disease
Authors: Cofer Lucas , Soomro Qandeel , Xia Yuhe , Luttrell-Williams Elliot , Myndzar Khrystyna , Rockman Caron , Charytan David , Berger Jeffrey S
Published: March 2022

Background:
End-stage kidney disease (ESKD) and peripheral artery disease (PAD) are frequently co-prevalent and each associated with increased cardiovascular (CV) risk. Platelets drive PAD pathogenesis and mediate atherothrombosis. Their function and influence on CV risk in ESKD remain unclear. We hypothesized that ESKD is associated with heightened platelet activity and incident cardiac and limb events in patients with PAD.

Methods:
The Platelet Activity and Cardiovascular Events study enrolled 289 patients with PAD undergoing lower extremity revascularization (LER). We measured platelet activity prior to LER via light transmission aggregometry in response to submaximal ADP, collagen, serotonin, epinephrine, and arachidonic acid. We followed patients for a median of 18 months for a primary endpoint of major adverse CV event (MACE; MI, stroke, death) and a secondary composite of major adverse CV or limb event (MACLE; MACE or acute limb ischemia).

Results:
Among enrolled subjects, 25 (9%) had ESKD. They were younger and more likely to have a history of coronary artery disease (CAD), heart failure, and critical limb ischemia (CLI) than those without ESKD (P<0.05 for each). Aggregation in response to epinephrine 2.0 uM after 5 minutes and at maximum was greater in those with compared to without ESKD (61% vs. 48%; P=0.004 and 77% vs. 60%; P=0.001, respectively). After multivariable adjustment, patients with vs. without ESKD were at greater risk for CV events (
Figure
). Platelet aggregation in response to submaximal epinephrine stimulation had a 32% and 45% mediating effect on the excess risk for MACE and MACLE, respectively, associated with ESKD (
Figure
).

Conclusions:
In patients with PAD, ESKD was associated with increased platelet aggregation in response to submaximal epinephrine that partially mediated increased risk for incident cardiac and limb events. Platelet activity appears to be an important mechanism underlying CV risk in ESKD.
Abstract 11422: Galactosyltransferase 1-Associating Protein Prevents Murine Vascular Runx2 Expression, Osteogenesis and Calcification
Authors: Gao Song , Gao Shanshan , Sun Zhen , Akesson Mikael , Shelat Harnath S , Geng Yong-jian
Published: March 2022

Introduction and Hypothesis:
The ubiquitin-conjugating enzyme, galactosyltransferase 1-associating protein (GTAP), is an E2 ubiquitin-conjugating enzyme (UBE2q1), involved in stem cell proliferation and differentiation. Increased vascular smooth muscle cell (SMC) calcification characterizes atherosclerotic heart disease. We tested here the hypothesis that GTAP plays a role in regulation of SMC calcification and expression of the osteogenic protein Runx2.

Methods and Results:
Echocardiography was conducted in sv129 (WT) (n=10) and GTAP-knockout (GTAP
-/-
) (n=11) mice, displayed reduced contractility in GTAP
-/-
vs. WT mice. In histopathology patch myocardial fibrosis, arterial hyperplasia and calcification occurred in GTAP
-/-
but not WT mice. Significantly increased calcium contents/dry proteins were found in the aortic rings of GTAP
-/-
vs. WT mice when ex vivo exposed to inorganic phosphate media for 9 days (Fig. 1a, p<0.05). To less extents, heterozygous GTAP
-/+
mice also had increased calcium contents. Total proteins were extracted from aortic SMC transduced with cDNA coding for WT GTAP and loss-functional mutant GTAP
C351A
for Western blot assays. As shown in Fig. 1b, compared with mock treated SMC, WT GTAP overexpressing SMC had increased band intensity of the contractile proteins, α-SM-actin and SM22α, but much lower band intensity of Runx2 protein. SMC with overexpression of the GTAP
C351A
mutant modestly reduction in Runx2 band density, and had little impact on band intensity of the contractile protein α-SM-actin and SM22α.

Conclusions:
GTAP exerts protective effects on vascular SMC by inhibiting expression of Runx2 and calcification, while promoting expression of the contractile proteins, α-SM-actin and SM22α.
Abstract 11425: Vascular Organ-Chips Made from Blood
Authors: Mathur Tanmay , Tronolone James J , Jain Abhishek
Published: March 2022

Introduction:
Organ-on-chip technology has accelerated
in vitro
preclinical research of the vascular system, and a key strength of this platform is its promise to impact personalized medicine by providing a primary human cell-culture environment where endothelial cells are directly biopsied from individual tissue or differentiated through stem cell biotechniques. But these methods are difficult to adopt in labs and limit the power of organ-chips in making accurate physiological predictions.

Hypothesis:
In this study, we report Blood Outgrowth Endothelial Cells as a suitable alternative to primary and iPSC-derived endothelial cells. Through organ-chip and RNA sequencing, we further demonstrate that patient-blood derived BOECs are disease-specific and can differentiate sickle cell disease (SCD) patients.

Methods:
We isolate BOECs from healthy blood samples and compare their genotype, phenotype and organ-chip functional characteristics against commercially available and most commonly used HUVECs and iPSC-derived endothelial cells. To study patient-specificity, we isolate BOECs from two clinically distinct SCD patients and compare the presence of proinflammatory and endothelial activation pathways as predicted by RNA sequencing of autologous BOECs. Finally, we study the differences in thromboinflammation and endothelial activation between patient BOECs through vessel-chips.

Results:
Blood-derived endothelial cells exhibit the gold-standard hallmarks of typical endothelial cells. BOECs exhibit the classic endothelial “cobblestone” morphology
in vitro
and exhibit growth rates, migration abilities,
de novo
vessel formation, response to fluid shear and exogenous cytokine stimulation in a manner comparable to HUVECs and iECs. When isolated from SCD patients, BOECs exhibit an activated state as predicted by differential gene expression (DGE) and pathway analysis. Finally, real-time healthy whole blood perfusion through endothelialized vessel-chips with BOECs from more severe SCD patient yielded higher platelet adhesion compared to patient with mild severity.

Conclusions:
Blood-derived endothelial cells may be employed in preclinical research for developing more robust and personalized next-generation disease models.