bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 21160: Predictors of Early Readmission and Complications Associated With Atrial Flutter Ablation
Authors: Tripathi Byomesh K , Arora Shilpkumar , Patel Nilay , Mishra Abhishek , Lahewala Sopan , Patel Neil , Kumar Varun , Dave Mihir , Badal Madan , Patel Nirali , Patel Prashant , Kagalwala Mustafa , Patel Nilesh , Gopalan Radha
Published: March 2022

Introduction:
Atrial flutter (AFL) ablation is associated with significant complications. Recognition of predictors of worse outcomes early is critical.

Methods:
National Readmission Data (NRD) 2013-14 was utilized to select study cohort and AFL and Cather ablation were identified using International Classification of Diseases, 9th Revision (ICD-9-CM) diagnostic code 427.32 and procedure code 37.34 respectively. Admissions within 90 day of index admission were considered as early readmissions. Cox proportional hazard regression and hierarchical two level logistic models were used to evaluate predictors of early readmission and complications.

Result:
A total of 1010 patients were readmitted (18.36%). Significant predictors of early readmission included [Hazards Ratio (HR), 95% confidence interval (CI), p-value] heart failure (HR: 1.30, 95% CI: 1.13 - 1.49, p < 0.001), chronic pulmonary disease (HR: 1.37, 95% CI: 1.18 - 1.58, p < 0.001), anemia (HR: 1.23, 95% CI: 1.02 - 1.49, p = 0.035), malignancy (HR: 1.87, 95% CI: 1.40 - 2.49, p<0.001), weekend admission(HR: 1.23, 95% CI: 1.02 - 1.47, p = 0.029) compared to weekday admission, index hospitalization length of stay of 3 to 4 days(HR: 1.29, 95% CI: 1.09 - 1.52, p = 0.003) and ≥ 5days (HR: 1.39, 95% CI: 1.16 - 1.65, p < 0.001) compared to length of stay of ≤2 days. (Figure 1A) Overall complication rate of 4% was noted. Cardiac complications were most common. Predictors of complications (odds ratio=OR, 95% confidence interval= CI, p-value) were diabetes (OR:1.50, CI-1.18-1,92, p<0.001), heart failure (OR:1.44, CI:1.12-1.85, p=0.005), peripheral vascular disease (OR:2.62, CI-1.87-3.69, p<0.001) and anemia (OR:2.02, CI-1.45-2.80, p<0.001). (Figure 1B)

Conclusion:
Identification of high risk population based on certain pre-existing conditions can have improved outcomes in patients undergoing AFL ablation.
Abstract 21161: Use of an Open Access Multi-Sponsor Data Sharing Platform in Cardiology
Authors: Vaduganathan Muthiah , Nagarur Amulya , Qamar Arman , Patel Ravi B , Navar Ann Marie , Peterson Eric D , Bhatt Deepak L , Fonarow Gregg C , Yancy Clyde W , Butler Javed
Published: March 2022

Background:
Sharing of patient-level clinical trial data has been widely endorsed, yet little is known how extensively these have been utilized in cardiology.

Methods:
We extracted data from ClinicalStudyDataRequest.com (CSDR), a large, multi-sponsor, open access platform hosting patient-level data from completed studies sponsored by 13 pharmaceutical companies.

Results:
From January 2013 to May 2017, the platform had data from 3,374 clinical trials of which 537 (16%) were specific to cardiometabolic therapeutics (phase 1 36%; phase 2 17%; phase 2/3 1%; phase 3 42%; phase 4 4%). These covered 74 therapies and 398,925 patients (
Figure 1
). Diabetes mellitus (60%) and hypertension (15%) were the most common study topics (
Figure 2
). Median time from study completion to data availability was 79 months. As of March 2017, CSDR had received 305 submitted proposals, of which 154 had signed data sharing agreements. Thirty of these proposals were related to cardiometabolic therapies and requested data from 81 unique studies (90% of which were phase 3/4). Most proposals were from the US (53%) and half did not report a funding source. Most proposals focused on
post hoc
exploratory analyses, research methodology, or meta-analyses; only 2 re-analyzed the original study primary hypothesis. To date, 3 peer-reviewed papers have been published (median 19 months from the data sharing agreement).

Conclusions:
Although data from over 500 cardiometabolic trials have been made available on a large, multi-sponsor open access platform, only 15% of these trials have been accessed by investigators thus far and few findings have reached publication.
Abstract 21169: Abnormal Left Atrial Mechanics Associate With Embolic Events in Light-Chain Cardiac Amyloidosis
Authors: Mussinelli Roberta , Lohrmann Graham , Perlini Stefano , Sanchorawala Vaishali , Ruberg Frederick L , Gopal Deepa M
Published: March 2022

Introduction:
Cardioembolic events are common in cardiac amyloidosis (CA) in the absence of atrial fibrillation. In sinus rhythm (SR), marked reduction in the atrial component of left ventricular filling confers a physiology of atrial electromechanical disassociation (EMD), an entity well-recognized in CA. Presently, there are no effective tools to predict risk for atrial EMD.

Hypothesis:
We hypothesized that detection of blunted left atrial (LA) mechanics by strain imaging would provide increased sensitivity to detect abnormal LA contraction mechanics and associate with embolic events/intracardiac thrombus among CA patients in SR.

Methods:
Baseline echocardiograms were analyzed for LA strain (TomTec, Unterschleissheim, Germany) from a retrospectively identified cohort of n=46 CA patients, of whom n=17 developed an embolic event/intercardiac thrombus (event+) and n=29 did not (event-). Patients with prior/active atrial fibrillation or flutter or administration of anticoagulation were excluded by electrocardiographic or medical record review. Comparisons between groups applied Student’s
t
test utilizing equal variance assumption testing.

Results:
No significant differences were identified in standard structural echocardiographic parameters (between event+ vs. event- groups), including LVEF (44 vs. 50%, p=0.11), transmitral A velocity (51 vs. 49 cm/s, p=0.84), LA volume index (41 vs. 40 mL/m
2
, p=0.77), and diastolic dysfunction grade (Grade III in 47 vs. 52%, p=0.53). In patients with light-chain CA, LA contraction mechanics were significantly decreased among event+ persons compared to event- persons (Figure).

Conclusions:
LA contraction mechanics are significantly blunted in light-chain CA patients who experienced an embolic event/intracardiac thrombus despite normal SR. These data suggest that LA strain assessment may afford a means to guide anticoagulation treatment in high-risk CA patients.
Abstract 21182: Single-Cell Sequencing Analysis Reveals Impaired Adipose Tissue Stem Cell Program in Obesity
Authors: Li Chuan , Tseng Alexander M , Huang Zheping , Dong Willie , Vella Anthony , Zhou Beiyan
Published: March 2022

The properly programmed “stemness” of tissue specific stem cells, including adipose tissue stem cells (ASCs), is the core feature for their function of tissue regeneration. Although ASCs harbor great potential for clinical application, it is poorly understood how ASCs respond to obesity, an affliction now affect over one third of the national population and health risks of cardiovascular diseases. We recently identified a set of cell surface markers to enrich ASCs from murine visceral adipose tissue. We observed that adipose tissue stromal cells bearing CD45
-
CD31
-
Sca-1
+
CD49f
-
CD34
+
were highly enriched for cells with sphere-initiation and multilineage differentiation capacity. Interestingly, the frequency of ASCs was markedly reduced in obese visceral stroma and their capability to derive multilineage progeny were severely impaired, compared to those in lean mice. Given the heterogeneity of isolated ASCs, we performed single cell sequencing analysis to understand mechanisms underlying the impaired “stemness” of obese ASCs. Freshly isolated ASCs from obese or age matched lean mice were subjected to single cell library generation (10X Genomics), followed by high-throughput sequencing. An average of 5500 UMI (unique molecular index) were detected in each cell and a total of 18,835 genes were detected in each sample (mapped to mm10). Interestingly, ASCs isolated from lean or obese adipose tissue displayed distinct pattern after K-mean clustering. Further, functional analysis revealed that critical networks in ASCs are significantly altered under obese conditions, including suppressed adipogenic program initiation and impaired impaired antioxidative defense. Further, multiple signaling networks triggered by both innate and adaptive immune responses displayed high activation Z-score in obese ASCs than that in lean ASCs. Overall, our results suggested that obesity severely impaired ASCs “stemness”, which may be attributed to multiple factors in obese adipose tissue, including the proinflammatory microenvironment. Further analyses of these profiles will provide critical information on how obesity alters the “stemness” program in ASCs and how to “revive” obese ASCs tissue regenerative ability.
Abstract 21185: Predictors of High Risk of Acute Coronary Syndrome in Diabetes: An Endothelial Damage Biomarker Approach
Authors: Cordola Hsu Amber R , Fan Wenjun , Harrington Douglas S , Wong Nathan D
Published: March 2022

Background:
Patients with diabetes mellitus (DM) are at increased risk of acute coronary syndrome (ACS); however, the factors predicting those at highest risk are not well-understood. We identified demographic and standard risk factors that best predict those at high risk based on a multiple biomarker algorithm.

Methods:
We studied adults with DM from a clinical registry who had measures of the PULS score (GD Biosciences, Irvine, CA), a biomarker algorithm identifying endothelial damage and predicting 5-year ACS risk consisting of HGF, sFAS, Fas Ligand, Eotaxin, CTACK, MCP3, Il-16, HbA1c, HDL-C, as well as age, sex, DM, and family history of CHD. We identified the proportion of patients with DM at low (<3.5%), intermediate (3.5-<7.5%), and high (≥7.5%) risk of ACS based on PULS. Stepwise logistic regression providing odds ratios and 95% confidence intervals (CIs) examined the relationship of age, gender, and individual risk factors not part of the PULS algorithm with the likelihood of a high risk PULS score.

Results:
There were 668 adults with DM (females: 39.5%, ages 30 to 100, mean age 66.5 years). Of these, 6.0% had a low, 12.9% intermediate, and 81.1% high risk PULS score. In the stepwise logistic regression, independent predictors of a high risk PULS score included age, sex, hypertension, body mass index (BMI), and current smoking (table). Other risk factors and biomarkers, including apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB), ratio ApoB to ApoA1, total or LDL-cholesterol, triglycerides, very low density lipoprotein cholesterol, lipoprotein (a), systolic or diastolic blood pressure, hs-CRP, and small dense LDL were not associated with a high PULS risk score.

Conclusion:
We demonstrated that age, male gender, hypertension, BMI, and current smoking are key factors potentially identifying persons with DM at high risk of ACS based on an algorithm identifying endothelial damage. Further validation through prospective studies with actual ACS events are needed.
Abstract 21186: Amelioration of Myocardial Stunning in Pigs Undergoing Cp/cpb With Bkca Channel Activator Supplemented Cardioplegia
Authors: Sodha Neel R , Potz Brittany A , Sellke Frank W , Feng Jun , Kolodziejczak Martin , Cordeiro Brenda , Clements Richard T
Published: March 2022

Introduction:
Activation of mitochondrial large conductance Ca++-activated K+ channels (BKCa) is cardioprotective in cell and rodent isolated heart models of cardioplegic arrest and reperfusion. We previously demonstrated cardioprotection is associated with reduced mitochondrial ROS generation and reorganization of individual electron transport chain complexes into physically associated respiratory supercomplexes (SC) made of ETC complex I/III/IV. In this study, we examined the efficacy of BKCa activation during cardioplegic arrest in a clinically relevant large animal study using pigs subjected to CP/CPB and reperfusion.

Methods:
50 kg Yorkshire pigs of either sex were subjected to CP/CPB (hyperkalemic cold blood CP, 1 hr) with or without the BKCa activator mallotoxin (MTX (aka rottlerin)) supplied in the CP solution, followed by reperfusion (1hr). Pigs were instrumented with a PV catheter and IVC occlusions performed at baseline and 30 and 60 mins after weening from bypass. Following surgery, mitochondria were isolated and subjected to Blue-Native PAGE and immunoblotting of ETC complexes to visualize large (~100-1500 kD) mitochondrial SC.

Results:
Baseline hemodynamics were similar between groups. CP/CPB resulted in significant myocardial stunning in pigs as assessed by LVDP (pre 64.8 mmHg vs post 42.0, P<.05 ), +/-dP/dt (pre 971.4 and -911.8 vs post:588.0 and -541.0, P<.05 ), and end-systolic elastance (Ees: pre 1.28 vs post .63, P=0.1 ) at 60 min reperfusion. However, pigs arrested with CP containing MTX (500 nM) exhibited greatly reduced myocardial stunning with significant improvements in LVDP (pre:65.7 post:67.8 mmHg, P<.01 vs post CP/CPB group) +/- dP/dt (pre:1026.0 and -911.8 vs post:1441.7 and -984.8 mmHg/s, P=.02 and .04 vs CP/CPB) and Ees (pre 1.1, post 1.35, P=.02 vs CP/CPB). LV mitochondria isolated from both groups had two major I/III/IV mitochondrial SC’s of ~1300 (SC1) and ~1000 kD (SC2) as assessed by BN-PAGE and immunoblot. The CP/CPB + MTX group had significant increases in both SC1 (6.0 % vs 18.0%, P=.01) and SC2 (19.7% vs 52.3%, P<.01) expressed as percent of total assembled complex IV.

Conclusion:
Addition of a BKCa activator to CP solutions ameliorates myocardial stunning in large animals subjected to CP/CPB and reperfusion.
Abstract 21191: Low Diastolic Blood Pressure (DBP) and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction (HFpEF) and Hypertension (HTN): Findings From Medicare-Linked OPTIMIZE-HF Registry
Authors: Lam Phillip H , Dooley Daniel J , Fonarow Gregg C , Ahmed Ali
Published: March 2022

Background:
According to the 2017 update of the 2013 ACCF/AHA HF guideline, systolic BP (SBP) should be lowered to <130 mmHg in euvolemic patients (pts) with HFpEF and persistent HTN. However, little is known about the role of low DBP on outcomes in these patients.

Methods:
Of the 10482 hospitalized pts with decompensated HFpEF (EF >40%) discharged alive, 5514 had HTN, defined as SBP ≥140 or DBP ≥90 mmHg on both admission and discharge, or if BP was normal (SBP <140 and DBP <90 mmHg), by use of anti-HTN drugs (CCBs, hydralazine, or both ACEI/ARBs and beta-blockers) both on admission and discharge. To minimize confounding by low SBP, we excluded 1810 pts with discharge SBP <130 mmHg. Of the remaining 3704 pts, 1571 had a discharge DBP <70 mmHg. Propensity scores for DBP <70 mmHg, estimated for each of the 3704 pts, were used to assemble a cohort of 1238 pairs of pts, with a discharge DBP <70 vs ≥70 mmHg, balanced on 40 baseline characteristics including discharge SBP. The 2476 matched pts (66% women, 10% African American) had mean (±SD) age of 78 (±10) years, EF of 57 (±8) %, and discharge DBP of 70 (±11) mmHg.

Results:
During 6 (median, 3) years of follow-up, all-cause mortality occurred in 69% and 65% of matched pts with a discharge DBP <70 vs ≥70 mmHg, resp. (HR, 1.11; 95% CI, 1.004-1.22; p=0.042; Figure). HF readmission occurred in 50% and 47% of matched pts with DBP <70 vs ≥70 mmHg, resp. (HR, 1.17; 95% CI, 1.05-1.31; p=0.007). There was no association with all-cause readmission (HR, 1.05; 95% CI, 0.96-1.14).

Conclusions:
In patients with HFpEF and HTN with SBP≥130 mmHg, a discharge DBP of <70 mmHg was associated with higher risk of mortality or morbidity.
Abstract 21196: Low Prevalence of Ideal Cardiovascular Health and Its Association With Job Strain
Authors: Muniz Davi D , Siqueira Kamile S , Cornell Cristina T , Fernandes da Silva Miguel M , Muniz Pascoal T , Silvestre Odilson M
Published: March 2022

Introduction:
Ideal Cardiovascular (CV) Health is characterized by four ideal lifestyle parameters and absence of cardiovascular risk factors.

Hypothesis:
The prevalence of ideal CV health is low in the Amazon Basin and it is negatively influenced by job strain.

Methods:
Job strain was evaluated in 479 employees from a academic center in the Amazon Basin by a validated Portuguese questionnaire that classified the participants as passive (low latitude decision and low job demand), active (high decision latitude and high job demand), low strain (low demand and high latitude decision) or high strain (high demand and low latitude decision). CV health was evaluated according to the AHA by 7 behaviours and risk factors (diet, physical activity, BMI, smoking, hypertension, diabetes and dyslipidemia). Individuals CV health status was classified as: ideal (ideal lifestyle and absence of cardiovascular risk factors), intermediate (intermediate at any parameter) or poor (when any of the seven factors was poor). We used logistic regression adjusted for age, gender, family income and educational level.

Results:
Mean age 44.3±12 years, 65% men. None participant had ideal CV health. Intermediate CV health was found in 44 (9%) and poor in 434 (91%) individuals. Considering low strain as a reference group, we found that high strain, active and passive had a non-significant (p> 0.05) increase in the chances of having poor CV health. When adjusting for confounders, having a high job strain was associated with poor BMI (> 30 kg/m
2
), OR 2.11, 95%CI 1.06-4.22; p=0.034) and poor diet OR 2.31, 95%CI 1.29-4.13; p = 0.005.

Conclusions:
In a population sample with a high prevalence of poor CV health, we found that job strain was associated with obesity and poor diet. Given the lack of participants with ideal CV health, policies focusing on health education and lifestyle interventions are paramount to this population, particularly those with higher job strain.
Abstract 21208: Association Between Serum Collagen and Myocardial Fibrosis Assessed by Magnetic Resonance Imaging: The Multi-Ethnic Study of Atherosclerosis
Authors: Ambale Venkatesh Bharath , Shenoy Chetan , Gross Myron , Sanchez Otto A , Kizer Jorge R , Guallar Eliseo , Ix Joachim , Tracy Russell , Wu Colin O , Jacobs David R , Duprez Dnaiel A , Bluemke David A , Lima Joao A
Published: March 2022

Introduction:
C-terminal telopeptide of procollagen type I (ICTP) and N-terminal propeptide of procollagen type III (PIIINP) are two of the major collagen turnover markers representing collagen degradation and synthesis. Cardiac magnetic resonance (CMR) using delayed enhancement (DE) and T1 mapping, provides a tool for detection and quantification of focal scar and diffuse interstitial myocardial fibrosis.

Hypothesis:
Levels of the serum biomarkers of ICTP and PIIINP at baseline are associated with the presence of myocardial scar and diffuse interstitial fibrosis at the 10-year follow-up.

Methods:
Of 3000 participants in a case(CVD)-cohort study that measured PIIINP and ICTP in baseline, 827 subjects with had CMRI at follow-up. Participants were initially aged 45-84 years and free of clinical CVD. Baseline serum PIIINP and ICTP concentrations were assayed using radio-immunoassay. DE-CMRI assessed myocardial scar at 10-year follow-up, with T1 mapping indices of extracellular volume fraction (ECV), pre-contrast T1, and T1 at 25 minutes post-contrast measuring diffuse interstitial fibrosis. Logistic (DE scar vs. absence as a dichotomous outcome) or linear (continuous values of T1 indices as outcomes) multivariable regression analysis with ICTP and PIIINP levels weighted for the design as continuous exposures were performed with adjustment for ACC-AHA ASCVD risk score and glomerular filtration rate at baseline (Model 1) and follow-up (Model 2).

Results:
Mean (SD) ICTP was 3.1 ± 0.9 μg/L; PIIINP was 5.4 ± 1.3 μg/L; ECV was 27.3 ± 3.1 %; and T1 at 25’ was 517 ± 42 ms. Among 827 participants, 68 had myocardial scar. Increased ICTP and PIIINP levels at baseline were associated with the presence of myocardial scar at follow-up (Table 1). ICTP showed no association with T1 mapping indices.

Conclusions:
Increased levels of collagen turnover markers were independently associated with the presence of myocardial scar 10 years later, but not with diffuse interstitial fibrosis.
Abstract 21211: Serial OCT Evaluation of Stent Apposition and Longitudinal Deformation of Cobalt-Chromium versus Platinum-Chromium Everolimus Eluting Stents
Authors: Thondapu Vikas , Hayat Umair , New Gishel , Raffel Christopher , Walters Darren , Lowe Harry , Proimos George , Freeman Melanie , Van Gaal William , Koshy Anoop , Chow Dominic , Whitbourn Robert , MacIsaac Andrew , Barlis Peter
Published: March 2022

Introduction:
Despite advances in coronary stent design, restenosis and thrombosis remain rare but potentially serious complications that may be related to stent malapposition and longitudinal deformation. As such, the aim of this study was to evaluate stent apposition, tissue coverage and longitudinal deformation in two second-generation everolimus-eluting stents (EES) with serial optical coherence tomography (OCT).

Methods:
Sixty patients recruited from 5 interventional cardiology centers were randomized (1:1) to receive either the cobalt-chromium (CoCr) EES or platinum-chromium (PtCr) EES (n=30 in each group). Patients had OCT imaging after nominal and high-pressure post-dilation and at 6 months, with 12 month clinical follow up. Strut apposition and stent length were measured by OCT at each time point. The primary endpoint was the percentage of struts malapposed before and after optimal post-dilation. Secondary OCT endpoints were percent of struts apposed and covered at 6 months and percent change in stent length, classified as mild (<5%), moderate (5-10%) or severe (>10%).

Results:
All results are presented as CoCr-EES versus PtCr-EES. A total of 38,948 struts were analysed by OCT. After nominal dilation, the percent of malapposed struts was 12.4% versus 15.8% (p=0.34). After post-dilation the percentage malapposition was 9.5% versus 10% (p=0.81). At 6 months, the percentage of struts covered and apposed was 81.7% versus 81% (p=0.87). There was no significant difference between groups in the mean change in stent length (nominal: 6.38% versus 4.26%, p=0.24; post-dilation: 4.18% versus 4.97%, p=0.52; 6 months: 6.91% versus 8.61%, p=0.49). However, at 6 months the PtCr-EES manifested significantly more cases of severe change in stent length (>10%) than the CoCr-EES (2 versus 8 cases, p=0.03) but were not associated with adverse clinical events during the study period.

Conclusions:
Both CoCr-EES and PtCr-EES stents demonstrate high rates of apposition and tissue coverage over 6 months with no significant differences in clinical outcomes. The PtCr-EES stent may be more susceptible to late stent deformation at 6 months but the true incidence, mechanisms, and clinical significance are as yet unclear.
Abstract 21217: PTP1B is a Critical Mediator for Vascular Smooth Cell Proliferation in the Development of Pulmonary Hypertension in vivo and in vitro
Authors: Moazeni Shayan , Ruffenach Greg , Umar Soban , Sarji Shervin , Cunningham Christine , Vaillancourt Mylene , Eghbali Mansoureh
Published: March 2022

Background:
Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling that leads to right ventricular failure and death. In PH, vascular remodeling is driven by hyper-proliferative and anti-apoptotic pulmonary arterial smooth muscle cells (PASMC). Protein Tyrosine Phosphatase 1B (PTP1B), is a negative regulator for apoptosis and proliferation of vascular smooth muscle cells through down-stream mediators such as BCL-2. While BCL-2 is increased in PH patients, the pathways for regulating BCL-2 are poorly understood. Therefore, our aim is to investigate if PTP1B has a role in PASMC proliferation and resistance to apoptosis in human PASMCs and in the angioproliferative Sugen/Hypoxia/Normoxia (SuHx) PH rat model.

Method:
Male Sprague-Dawley rats were treated with a single intraperitoneal dose of a vascular endothelial growth factor antagonist (SU5416, 20 mg/kg, n=4) and kept in hypoxia for 3 weeks followed by normoxia for 2 weeks. Saline treated controls were kept in normoxia for 5 weeks (n=4). RV systolic pressure (RVSP) was recorded by RV catheterization and hearts were isolated to assess RV hypertrophy (RV/LV + IVS). PTP1B and BCL-2 expression was determined using qPCR. Healthy hPASMCs were incubated with a PTP1B inhibitor (Ethyl-3,4-dephostatin) at IC50=0.58ug/ml for 24hrs and stained with Ki67 to assess for proliferation.

Results:
SuHx rats had severe PH, evident by elevated RVSP compared to control (88.97+/- 13.67 vs. 28.47+/- 2.22 mmHg, p<0.05). PH rats also showed reduced RV function and increased hypertrophy (0.7+/- 0.063 vs 0.274 +/-0.01 in control, p<0.05). PH lungs exhibited pulmonary vascular remodeling characterized by excessive growth of the PASMCs. PTP1B was decreased in PH lungs compared to controls (0.158+/-0.0647 vs 1+/-0.06, P<0.05). As expected, BCL-2 expression was significantly increased in PH compared to control (2.01+/-0.162 vs 1 +/-0.1, P<0.01). Inhibition of PTP1B in cultured hPASMCs increased proliferation by ~2 fold as assessed by Ki67 positive cells.

Conclusion:
Severe Angioproliferative PH in rats is associated with a downregulation of PTP1B and increased expression of BCL-2. Additionally, PTP1B inhibition resulted in hPASMC proliferation, suggesting a role for PTP1B in the pathogenesis of PH.
Abstract 21230: Mortality in Coronary Disease Following Cardiac Rehabilitation: Focus on Weight Loss or Lean Mass?
Authors: Kachur Sergey , Morledge Michael , Lavie Carl J , Alban De Schutter , Arena Ross , Milani Richard
Published: March 2022

Introduction:
Cardiac rehabilitation (CR) in stable coronary heart disease (CHD) has been shown to improve mortality commensurate with levels of improvement in cardiorespiratory fitness (CRF) and lean mass. The current study examines the effects of changes in LM in determining mortality outcomes after CR.

Hypothesis:
Effects of weight changes on mortality are influenced by the obesity paradox; stratifying weight changes by lean mass (LM) will help differentiate healthy from unhealthy weight loss.

Methods:
1110 subjects with stable CHD referred for CR between 01/2000 and 06/2013 with a mean follow-up of 6.3 years were stratified according to median change in peak oxygen consumption (VO
2
) measured during maximal cardiopulmonary exercise testing and median change in LM index (LMI). Mortality differences were adjusted for age, sex, baseline VO
2
, ejection fraction, and body mass index.

Results:
Changes in weight following CR were not a significant predictor of mortality. Likewise, changes in waist circumference and LMI were not significant independent predictors of mortality. However, change in LMI when combined with change in peak VO
2
yielded significant prognostic information between those in the top and bottom 50
th
percentile of peak VO
2
changes (HR 2.58; 95% CI 1.54-4.33; p < 0.001) and a strong trend toward significance for lower mortality in individuals who gain LMI (HR 1.72; 95% CI 0.99-2.97; p = 0.05). (
Figure 1
)

Conclusions:
In patients with CHD, stratifying changes in LM by peak VO
2
has the potential to gauge the response to exercise training and associated mortality benefits than each measure alone. Further study is needed to determine if targeting both increases in VO
2
and LMI can lead to better outcomes in patients enrolling into CR.
Abstract 21241: One Device Closure for Multiple Atrial Septal Defects Guided With Thoracic Echocardiography: The Role of Personalized Three-Dimensional Printing
Authors: Pan Xiangbin
Published: March 2022

Introduction:
Single device closure for multiple atrial septal defects (ASD) is still challenging due to the complicated anatomy and technical difficulty. The emerging three-dimensional (3D) printing facilitates the identification anatomical structure, helps the procedural planning and simplifies the imaging monitoring for the transcatheter closure.

Hypothesis:
We therefore aimed to testify the possibility of single device for multiple ASDs under the guidance of transthoracic echocardiography with the aid of 3D printing models in this prospective study.

Methods:
Stereolithography data was acquired with cardiac CT scan in 30 patients (20±16 years, 18 females) having multiple ASDs and personal 1:1 scale 3D printed model was printed. Closure planning, including determination of target defect, occluder selection and device placement, was attempted on the model before intervention. Transcatheter closure was performed under the guidance of transthoracic echocardiography. The conventional selection of device was compare to the method based on 3D models. The clinical effect was assessed immediately after device closure and at 3-month follow-up.

Results:
3D printing model was successfully established in all patients and 26 cases were suitable for transcatheter closure according to model test. Transcatheter closure with single device was completed in 26 patients (including 14 patients with defect distance >7mm) even under the guidance of the transthoracic echocardiography without complications.Compared to conventional method, device selection was more accurate in 3D model. Immediate postoperative echocardiography demonstrated mild residual shunt in 5 patients whereas disappeared in 3 patients and decreased in the other 2 patients at 3-month follow-up.

Conclusions:
3D printing technology and echocardiography guiding procedure enables single device for closure of multiple ASDs including challenge cases.
Abstract 21251: Lipase Maturation Factor 1 Plays a Lipase-Independent Role in Energy Metabolism and Adiposity
Authors: Ehrhardt Nicole , Mao Hui , Bedoya Candy , Peterfy Miklos
Published: March 2022

Vascular lipases including lipoprotein lipase (LPL), hepatic lipase (HL) and endothelial lipase (EL) are important determinants of plasma lipid homeostasis and coronary artery disease risk. The ER-resident lipase-chaperone Lipase Maturation Factor 1 (LMF1) plays a key role in the biogenesis of active vascular lipases and plasma lipid metabolism. While mice and humans harboring loss-of-function mutations in LMF1 exhibit deficiencies in all three vascular lipases and hypertriglyceridemia, detailed metabolic characterization of LMF1 deficiency has been hampered by the neonatal lethality of LMF1-/- mice. The goal of the present study was to investigate the metabolic consequences of combined lipase deficiency in the adult mouse. To overcome the lethality associated with whole-body LMF1 deficiency, we pursued a transgene rescue strategy involving cross-breeding of Mck-LMF1 transgenic and LMF1-/- mice. Mice expressing LMF1 exclusively in muscle tissue (Mck-LMF1-/-) exhibited normal survival and plasma lipid levels indicating that restoration of LPL activity in muscle only is sufficient to normalize plasma lipid metabolism in LMF1-/- mice. However, Mck-LMF1-/- mice also demonstrated decreased body weight (BW) and adiposity, reduced hepatic steatosis and improved insulin sensitivity; phenotypes that have not been observed in single-lipase deficient mouse models. Mechanistic studies revealed that decreased energy expenditure was responsible for diminished BW in Mck-LMF1-/- mice. To investigate the role of adipose tissue in this phenotype, we generated adipose-specific LMF1 knock-out (Ad-LMF1-KO) mice. While Ad-LMF1-KO mice exhibited hypertriglyceridemia, BW and adiposity remained unaffected indicating that adipose tissue was not the driver of lean phenotype in LMF1 deficiency. Furthermore, normolipemic heterozygous LMF1+/- mice exhibited lower BW and adiposity relative to wild-type littermates. Finally, we observed direct correlation between hepatic LMF1 expression and adiposity across ~100 inbred mouse strains in the Hybrid Mouse Diversity Panel. In conclusion, our results implicate hepatic LMF1 expression in energy metabolism and suggest that LMF1 plays a novel, lipase-independent role in metabolic regulation.
Abstract 21262: Multi-Morbidity, Cardiac Disease and Cognition
Authors: Bratzke Lisa C , Carlson Beverly
Published: March 2022

Introduction:
Several chronic illnesses have demonstrated relationships to cognitive decline and risk of Alzheimer’s disease (AD); however, researchers have largely ignored the effects of multi-morbidity (two or more chronic illnesses) on cognition and risk of AD. Multi-morbidity may mimic the early symptomology of AD and represent a modifiable risk factor for cognitive decline. Therefore, the purpose of this study is to examine the relationship between multi-morbidity and cognition in the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a longitudinal observational cohort with multiple waves of cognitive assessment.

Hypothesis:
We hypothesized that cognition would differ between the multi-morbidity subgroups.

Methods:
Latent class analysis (LCA) was completed to identify different subgroups of the 1,285 WRAP participants who were recognized based on their self-reported chronic illnesses. The final model was validated using several variables of interest (
i.e.,
biomarkers and depressive symptom scores). Chi-square tests were used to examine the association between multi-morbidity and cognitive status.

Results:
The LCA revealed a four-class model best fit solution, see Figure 1. Cholesterol was present across all four classes. Chi-square statistic revealed a significant difference in the proportion of participants with cognitive impairment between the classes (χ2 = 8.46, p = 0.03), with the largest differences observed between classes II (sleep) (19%) and III (cardiovascular) (9%) (p<0.01) and classes II (19%) and IV (healthy) (12%) (p<0.01).

Conclusions:
Findings offer initial evidence of an association between multi-morbidity clusters and the development of cognitive decline. Sleep and hypercholesterolemia may present a larger burden to cognitive health than previously reported. Disease management programs targeting optimal control of multiple cardiac illnesses may aid supporting optimal cognitive function and decreasing AD risk.
Abstract 21264: Age and Gender Related Left Atrial Remodeling With Magnetic Resonance Imaging: Multi Ethnic Study of Atherosclerosis
Authors: Ambale Venkatesh Bharath , Hong Seoyoung , Habibi Mohammadali , Lim Daniel , Wu Enpei , Jorgenson Neal , Hundley W. Gregory , Shea Steven J , Liu Kiang , Gomes Antoinette S , Heckbert Susan , Post Wendy S , Bluemke David A , Lima Joao A
Published: March 2022

Introduction:
Left atrial (LA) structure and function are associated with future cardiovascular (CV) events and risk factors. Studying the longitudinal change of LA structure and function with age may provide important insights into the natural history of LA remodeling.

Hypothesis:
The aim of this study is to evaluate associations between age and gender with longitudinal changes in LA remodeling in a large multi-ethnic cohort free of clinical CV disease at baseline.

Methods:
Cardiac magnetic resonance (CMR) was used to identify longitudinal changes in LA structure and function in 2882 MESA participants who underwent baseline (year 2000-2002) and 10-year follow-up CMR imaging. Multimodality tissue tracking (MTT, Toshiba) software was used to calculate LA structure (LA maximum, minimum and pre-atrial contraction volumes indexed to body surface area - LA Vmax, Vmin and VpreA) and function (LA total, passive and active emptying fraction, LATEF, LAPEF, and LAAEF). Data were analyzed with multivariable mixed-effects regression models in which the outcome was CMR LA measurements, and the covariates included follow-up time and CV risk factors (hypertension, diabetes, smoking, race/ethnicity, body mass index, and lipid levels).

Results:
Participants were aged 45-84 years at baseline, and 53% were women. At baseline, men had lower LATEF than women (58.4 vs 63.4%, p<0.05), while they had similar LA Vmax (30.3 vs 29.9 ml/m2, p=NS) and larger Vmin (13.1 vs 11.5 ml/m2, p=NS). Median time between baseline and follow-up CMR imaging was 9.4 years. Over this period, LA Vmax and Vmin increased in both men (by 4.8 and 5.2 ml/m2 respectively, p<0.05) and women (by 4.9 and 4.6 ml/m2 respectively, p<0.05); while LATEF decreased in both (-7.3 % in women, and -6.1% in men, p<0.05).

Conclusions:
In a population free of CV disease, at baseline women had higher LA function than men, as well as lower LA volumes. Aging was associated with increased LA volume and decreased LA function in both men and women.
Abstract 21277: Galectin 3 Predicts New Onset Heart Failure: Systematic Review and Meta Analysis of Prospective Studies
Authors: Nasir Usama , Qureshi Waqas T , Shahid Hania , Dutta Abhishek , Al-Mallah Mouaz
Published: March 2022

Background:
Galectin 3, a fibrosis biomarker, has found to have significant prognostic value in predicting all cause mortality in heart failure patients. However, its role in predicting the risk for new onset heart failure is not well established. We conduct a meta-analysis to analyze the correlation of increase in serum Galectin 3 levels from baseline and development of new onset heart failure.

Methods:
MEDLINE, EMBASE, CINAHL, Web of Science, meeting abstracts and Cochrane central databases were searched from inception till May 2017. 6 studies were included in the study. Hazard ratio, random effects model was used to estimate the correlation of increase in Galectin 3 levels with development of new onset heart failure. Between studies heterogeneity was assessed by I
2
method.

Results:
Pooled patient population comprised of 24,297 patients (mean age 59.1 years, 50.6% male). 1444 (5.9%) patients develop new onset heart failure. Mean baseline Galectin 3 levels were 16.7 ug/L. Patients were followed up for mean duration of 5 years. Increase in Galectin 3 levels from baseline was associated with significant increase in risk of new onset heart failure (1.86 [1.36-2.54], p = 0.0002). We noted considerable heterogeneity 80% between studies.

Conclusion:
This meta analysis showed that galectin 3 levels were directly associated with risk of new onset heart failure. Therefore, galectin 3 can help in early detection of new onset heart failure and hence can help in providing preventive strategies.
Abstract 21298: Surveillance Invasive Hemodynamics in Pediatric Heart Transplant Patients: Utility or Futility?
Authors: Arbon Kate S , Law Yuk M , Kirklin James K , Pruitt Elizabeth , Hoffman Timothy M , Schowengerdt Kenneth O , L'Ecuyer Thomas J , Kindel Steven J
Published: March 2022

Introduction:
Although first year survival after pediatric heart transplant is improving, late-onset rejection, cardiac allograft vasculopathy (CAV), and graft failure remain significant challenges. Patients routinely undergo endomyocardial biopsy with invasive hemodynamics as the gold standard for rejection surveillance and assessment of long-term graft performance. However, it remains unclear how hemodynamic measures contribute to the monitoring of rejection, CAV, and graft dysfunction. This study aims to assess changes in hemodynamics as the graft ages in patients with or without a history of rejection or CAV.

Hypothesis:
We hypothesize that abnormal hemodynamics, particularly elevated filling pressures, are associated with CAV, rejection and graft aging.

Methods:
A total of 2,764 patients from the Pediatric Heart Transplant Study database from 1995-2014 met study criteria of survival to 1 year after transplant with available surveillance biopsy and hemodynamics. Retrospective analyses of 16,489 hemodynamic sets were performed.

Results:
The median age at transplant was 4.89 years [0.73, 12.95]. Average follow up time was 4.05 years [2.04, 7.17]. Fifty-six percent of patients were male, and 46% had history of congenital heart disease. When comparing hemodynamics collected at the first annual catheterization to 10 years after transplant, those who never had rejection or CAV showed statistically significant increases in right atrial pressure (RAP) (p=<0.001), and pulmonary capillary wedge pressure (PCWP) (p = <0.001) with concomitant decrease in cardiac index (p=0.01). When comparing hemodynamics from patients with a history of CAV or rejection to those without such events, patients with history of CAV or rejection had higher RAP (p=<0.001) and PCWP (p = <0.001), and lower cardiac index (p=0.003) and systemic vascular resistance (p=0.0001).

Conclusions:
Despite freedom from CAV or rejection, RAP and PCWP increase and cardiac index decreases as the graft ages. Additionally, the diagnosis of CAV or rejection during the life of the graft leads to further derangement in graft performance, which can be detected in hemodynamics. Serial hemodynamic assessment may contribute to the ongoing monitoring of graft function in pediatric recipients.
Abstract 21301: Effect of Chest Compression Parameter Variation on Waveform Characteristics of the Ventricular Fibrillation Electrocardiogram
Authors: Salcido David D , Sundermann Matthew L , Koller Allison C , Sufrin Rena , Kucewicz John , Nichol Graham , Adedipe Adeyinka , Menegazzi James J
Published: March 2022

Introduction:
The ventricular fibrillation (VF) electrocardiogram (ECG) waveform is known to deteriorate over time if untreated, recover with CPR, and to predict defibrillation success. VF ECG measures could inform CPR quality feedback algorithms based on patient physiologic response.

Objectives:
Investigate the effects of chest compression parameters (rate, depth and duty cycle (DC)) on VF ECG waveform characteristics in a swine cardiac arrest model.

Methods:
Twelve mixed-breed domestic swine were sedated, anesthetized and paralyzed, followed by endotracheal intubation and mechanical ventilation. Animals were instrumented with a battery of physiological sensors, including multi-lead ECG, recorded continuously with a high-fidelity data acquisition unit at 1000Hz. VF was induced with a 3-second 100mA transthoracic shock. After 7 minutes, animals were randomized to receive continuous CPR with a custom robotic device using 1 of 6 pre-programmed, cross-over 2-phase CPR schemes that varied 1 parameter in 5 x 1-minute intervals per phase while holding the other 2 parameters fixed. Frequency (AMSA) and slope-based (MS) quantitative ECG characteristics of the ECG were calculated at the end of each 1-minute interval and compared between rate, depth and DC schemes, as well as experimental phases. Correlations between CPR parameter settings and ECG characteristics were calculated.

Results:
Compression rate showed a low-to-moderate correlation (0.454) with change in MS in Phase I, however neither DC nor depth showed a correlation with either AMSA or MS. In ANOVA models, MS differed between CPR groups at the end of Phase I (p = 0.046) but not AMSA, suggesting similar response of quantitative ECG measures after extended time intervals.

Conclusions:
In this study only chest compression rate in early phase CPR appeared to be related to quantitative characteristics of the VF ECG. Rate may be important clinically in the early phase of CPR.
Abstract 21306: Impact of Insulin Treated Diabetes Mellitus on 1 Year Outcomes After Contemporary PCI
Authors: Chandrasekhar Jaya , Sartori Samantha , Baber Usman , Shah Shrushti , Rabieihashemi Samaneh , Vogel Birgit , Farhan Serdar , Ge Zhen , Sorrentino Sabato , Sharma Madhav , Qadeer Abdul , Demopoulos Antonia , Snyder Clayton , Moazzami Kasra , Sudyn Alexander , Moreno Pedro , Kovacic Jason , Sweeney Joseph , Krishnan Prakash , Barman Nitin , Dangas George , Mehran Roxana , Kini Annapoorna , Sharma Samin
Published: March 2022

Background:
Insulin treated diabetes mellitus (ITDM) is associated with more extensive atherosclerotic disease and worse cardiovascular prognosis compared to non-ITDM patients.

Hypothesis:
We sought to examine 1-year outcomes in ITDM and non-ITDM patients compared to non-DM patients following contemporary percutaneous coronary intervention (PCI).

Methods:
We followed consecutive patients undergoing PCI at a large tertiary center from 2009-2016. Prospectively collected data were retrospectively examined. Patients were grouped based on DM and treatment status at baseline. 1-year outcomes were analyzed in a time to event manner and adjusted using multivariable Cox regression methods. Major adverse cardiovascular events (MACE) were defined as a composite of death, myocardial infarction (MI) or target vessel revascularization (TVR).

Results:
During the study period, 16,889 patients underwent PCI including 13.7% (n=2313) ITDM, 34.0% non-ITDM (n=5737) and 52.3% non-DM (n=8839) patients. ITDM and non-ITDM patients were younger than non-DM patients, with greater prevalence of females and non-white patients, higher body mass index and greater prevalence of prior revascularization and chronic kidney disease. ITDM patients were more likely to present with stable angina compared to others. With respect to angiographic characteristics, the prevalence of B2/C type lesions was similar between the groups. At 1-year, both ITDM and non-ITDM patients had greater risk of 1-year MACE and MI compared to non-DM patients, however ITDM patients had significantly higher rates of MACE, death, MI, and TLR (
figure
).

Conclusions:
The negative prognostic effect of DM following contemporary PCI is heightened in the presence of insulin treatment, compared to non-DM patients, despite use of contemporary PCI techniques and use of new generation DES.
Abstract 21311: A Novel, Shear-Assembling, Shear-Thinning Polymer-Nanoparticle Hydrogel Diminishes Post-Operative Thoracic Adhesions in a Rodent Model of Ischemic Cardiomyopathy
Authors: Stapleton Lyndsay M , Steele Amanda N , Thakore Akshara D , Goldstone Andrew B , Truong Vi N , Eskandari Anahita , Paulsen Mike J , Bourdillon Alexandra T , Yu Anthony C , Kawamura Masashi , Jaatinen Kevin J , Farry Justin M , Appel Eric A , Woo Y J
Published: March 2022

Objective:
The incidence of post-operative adhesions is estimated to be 93%, resulting in severe pain, bowel obstruction, infertility, and often requires re-operation. Mainstay adhesion prevention technologies are generally derived from polymer films that serve as physical barriers between scarring tissue and surrounding organs. Yet, these films have not been widely accepted due to their inability to adequately limit adhesions and difficulty handling during surgery. We hypothesized shear-thinning, self-healing polymer nanoparticle hydrogels (PNP) would instead provide a novel, viscoelastic barrier between tissues and organs, allowing tissues to move past each other similar to the body’s natural state, effectively preventing adhesion formation (Fig. 1A).

Methods:
PNP shear-thinning and self-healing behavior was characterized via rheometry. Adult male Sprague Dawley rats (n=23) underwent sham surgery or permanent ligation of the LAD followed by pericardial application of 250μL PNP gel, 1cm
2
Interceed®--a commercially available adhesion barrier, or no treatment. Degree of adhesion formation, cardiac function, infarct size, and immune response were assessed 4-weeks post infarction.

Results:
PNP exhibited fast, complete recovery of mechanical properties following network rupture at high strains indicating the reversible and robust nature of the hydrogel system. (Fig. 1B). Infarct size and ejection fraction were controlled to ensure similar inflammatory responses contributing to adhesion formation across treatment groups (1C and D). Treatment with PNP significantly reduced the development of adhesions compared to Interceed and untreated controls (Fig. 1E).

Conclusion:
Administration of a shear-thinning, self-healing hydrogel reduces the extent of adhesion formation in the thoracic cavity following a thoracotomy and myocardial infarction. PNP provides an easily delivered, scalable solution for post-operative adhesion prevention.