bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12929: Heterogeneity in Primary and Secondary Prevention Studies of Statins and PCSK9 Inhibitors: Does One Size Fit All?
Authors: Nandi Saheli , Brar Simarjeet , Dal'Bo Natalie , Ijaz Sardar , Ganatra Sarju , Dani Sourbha
Published: April 2022

Background:
We aim to assess the heterogeneity of demographics, gender variability and outcomes reporting for subjects enrolled in RCTs studying the role of statins and PCSK9 inhibitors in primary and secondary prevention of CAD.

Methods:
RCTs and metanalyses were searched for the use of statins and PCSK9 inhibitors published in journals with impact factor
>
4 between 1995 and 2020. RCT data was analyzed for gender, race and geographic location. Metanalyses were searched for the outcomes-level heterogeneity.

Results:
A total 31 statin-based RCTs for primary and secondary prevention of CAD were found, of which 29 were included with a total 172,871 patients (71.4% males vs. 28.6% females). In WOSCOPS trial, all 6595 subjects were males. Though most of these trials included global patient populations, 10% of the trials included exclusively North Americans. Fifteen of the RCTs (52%) did not have race data. Of the 14 RCTs which reported race: 67% White, 4% Black. The mean number of White and non-White patients were 3950 and 1768 respectively. For PCSK9 inhibitors with a total of 13 RCTs included in our study there were cumulative 85,806 patients with globally enrolled patient population and predominantly male 71% vs 29% females. Ten RCTs (77%) reported race: 82% White, 0.3% Black. The mean number of White and non-White patients were 4671 and 1058 respectively. The eleven statin metanalyses included 823,936 patients. Ten of the eleven metanalyses reported statistical heterogeneity via I
2
% (mean 53%) for different outcomes. Five of the eleven metanalyses included primary outcomes of all-cause mortality, and the rest included onset/progression of different types of cardiovascular disease. The seven PCSK9 inhibitor metanalyses pooled 376,885 patients. All 7 metanalyses reported heterogeneity via I
2
% (mean 48%) for different outcomes, of which 2 included primary outcomes of all-cause mortality.

Conclusions:
Significant gender and racial disparities exist in RCTs for primary and secondary prevention lipid lowering therapies. Enrollment in PCSK9 inhibitor trials was global and significant treatment effect heterogeneity existed in metanalyses. Inequalities in female and non-White participation may hamper generalizability of these crucial medications.
Abstract 12930: The Prognostic Value of Korean vs. Western Nomogram for Exercise Capacity in Korean Patients With Cardiovascular Disease
Authors: Park Soohyung , Lee Kyuho , Back Seungmin , Lee Jieun , Kang Dong , Kim Ji Bak , Choi Jah , Roh Seung-young , Na Jin O , Choi Cheol Ung , Kim Jin W , Rha Seung Woon , Park Chang Gyu , Seo Hong-Seog , Kim Eung Ju
Published: April 2022

Background:
Exercise capacity is known to be an independent predictor of cardiovascular events and mortality. However, most of previous studies were based on western population. Further study is warranted for Asian patients according to ethnic or national standard. We aimed to compare prognostic value of Korean and Western nomogram for exercise capacity in Korean patients with cardiovascular disease (CVD).

Methods:
In this retrospective cohort study, we enrolled 1178 patients (62 ± 11 years; 78 % male) who referred for cardiopulmonary exercise testing in cardiac rehabilitation program. Median follow-up was 1.6 years. Exercise capacity was measured in metabolic equivalents (MET) by direct gas exchange method during the treadmill test. The nomogram for exercise capacity from healthy Korean and previous landmark western study was used to determine the percentage of predicted exercise capacity. The endpoint was the composite of major adverse cardiovascular event (MACE; all-cause death, myocardial infarction, repeat revascularization and stroke) and hospital readmission for heart failure.

Results:
In multivariable cox proportional hazard analysis, the risk of primary endpoint was more than twice (hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.12-4.46) in the patients with lower exercise capacity (<85% of predicted) by Korean nomogram. The lower exercise capacity was the most powerful predictor following age and left ventricular ejection fraction. However, the lower exercise capacity by Western nomogram could not predict the primary endpoint (HR 1.28, 95% CI 0.81-2.04).

Conclusion:
CVD patients with lower exercise capacity have higher risk of MACE and readmission for heart failure. Considering inter-ethnic differences in cardiorespiratory fitness, Korean nomogram provides more suitable reference values to determine lower exercise capacity to predict cardiovascular events in Korean patients with CVD.
Abstract 12935: Lack of Correlation Between Echocardiographic Parameters and Cardiac Hemodynamics in Patients With Severe Aortic Stenosis
Authors: Ragheb Mirna , Eastman Triston , Ravandi Amir , Kass Malek , Shah Ashish
Published: April 2022

Introduction:
Aortic stenosis (AS) affects ~10% of population over 65 years of age. Severe AS is defined as mean trans-aortic pressure gradient (MG) of ≥40 mmHg and/or aortic valve area (AVA) of <1.0 cm
2
. Patients’ symptoms correlate with cardiac output, and the ability to augment with exercise. However, the relationship between AVA/MG and stroke volume/cardiac output is not well defined.

Hypothesis:
We aimed to identify the relationship between conventional echocardiography-based parameters (i.e., AVA/MG) and non-echocardiography-based hemodynamics in AS.

Methods:
Consecutive patients with severe symptomatic AS undergoing TAVI between June and September 2020 at St. Boniface Hospital in Manitoba, Canada were recruited. Hemodynamics was measured using whole-body impedance-based Non-Invasive Cardiac System (NICaS). Evaluated hemodynamics include stroke volume index (Svi), cardiac output (CO), cardiac index (CI), and total peripheral resistance (TPR) and were compared to conventional parameters.

Results:
Thirty patients (37% females; mean age 79.0 ± 1.7 years) were enrolled. Average MG was 41.8 ± 2.2 mmHg (16.94 - 70.0) and mean AVA was 0.81 ± 0.04 cm
2
(0.30 - 1.10). A linear regression model revealed a poor correlation between AVA and both Svi and CI (r
2
=0.012 and 0.025, respectively). Similarly, MG correlated poorly with Svi and CI (r
2
=0.017 and 0.024, respectively). Interestingly, 60% patients displayed a low-flow state (defined as Svi <35 ml/m
2
), despite a normal left ventricular ejection fraction (EF >50%, r
2
=0.011).

Conclusions:
There is incongruence between hemodynamics and conventional parameters defining severe AS. A subset of patients have low-flow state, despite normal left ventricular function. It is plausible that some of these patients, based on their hemodynamics, may benefit from valvular intervention earlier, even at a lower MG. Long-term hemodynamic assessment may guide identification of outcomes in AS patients post-TAVI.
Abstract 12936: A Critical Role of Deubiquitinase OTUB1 in Adaptive Cardiac Hypertrophy
Authors: Wang Wenjuan , Li Jie , Zou Jianqiu , Ayala Juan , Sun Shao-Cong , Su Huabo
Published: April 2022

Ubiquitin-mediated proteolysis is essential for protein homeostasis, and its defects lead to the development of various cardiomyopathies and heart failure. By reversing the ubiquitination and degradation of target proteins, deubiquitinases (DUBs) play a crucial role in protein homeostasis. However, the importance of DUBs in cardiac pathophysiology is largely unknown. Here we addressed the role of the DUB OTU domain aldehyde binding-1 (OTUB1) in the heart. Bioinformatics analysis reveals an upregulation of OTUB1 in hypertrophic and failing human hearts. In cultured cardiomyocytes, adrenergic agonists induced upregulation and activation of OTUB1. Silencing OTUB1 in repressed adrenergic agonists-induced fetal gene re-activation, protein synthesis and cardiomyocyte hypertrophy.
In vivo
, mice deficient of OTUB1 in the heart developed dilated cardiomyopathy and heart failure, leading to premature lethality. The severe cardiac phenotype is accompanied by lipid accumulation, ER dilatation, prevalent autophagic vesicles containing ribosomes, as well as dysregulated expression of metabolic and ribosome genes. Delivery of wild-type OTUB1, but not the enzymatic dead mutant, via AAV9 to OTUB1-deficient hearts attenuated cardiac dysfunction and prolonged the lifespan of mice. Mechanistically, loss of OTUB1 suppressed the degradation of Deptor, an inhibitory mTOR regulator, leading to impaired mTOR signaling in cultured cardiomyocytes and mouse hearts. Collectively, these findings suggest OTUB1 is required for physiological cardiac growth by fine-tuning mTOR signaling and identify OTUB1 as a novel regulator of cardiac homeostasis.
Abstract 12937: Sex Differences on Clinical Outcomes After Thoracic Endovascular Aortic Repair
Authors: Yousef Sarah , Brown James , Aranda-Michel Edgar , Serna-Gallegos Derek , Wang Yisi , Dunn-Lewis Courtenay , Sultan Ibrahim
Published: April 2022

Introduction:
Thoracic endovascular aortic repair (TEVAR) has been increasingly utilized for the treatment of descending thoracic aortic aneurysms and dissections. Further research is warranted to understand outcomes of TEVAR in various populations.

Hypothesis:
Sex will not influence outcomes after nonelective TEVAR.

Methods:
This was an observational study from the Nationwide Readmissions Database analyzing men (n=3903) and women (n=2691) with aortic aneurysm or Type B aortic dissection who underwent nonelective TEVAR from 2010-2017. Appropriate trend weighting was used to generate national estimates. International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes were used to identify patients with thoracic aortic aneurysms or dissections who underwent TEVAR. 30-day and 90-day readmissions, in-hospital mortality, postoperative complications, and cost were compared between the two groups. Mixed model logistic regression was used to determine predictors of readmission, treating each participating hospital as a random effect.

Results:
The study population consisted of 6594 patients (3903 men, 2691 women) who underwent nonelective TEVAR. In-hospital mortality was 9.3% (n=613) and was not significantly different between groups (9.85% in men vs 8.50% in women, p=0.06). Of the remaining 5981 patients, women were more likely than men to be older, to have chronic pulmonary disease, and to have aneurysm rather than dissection as their indication for TEVAR. Women were less likely to have chronic kidney disease. Postoperatively, women were less likely to develop respiratory failure (9.41% vs 11.75%), acute kidney injury (17.93% vs 33.87%), and mesenteric ischemia (2.63% vs 4.36%). On multivariable regression, female sex was not associated with an increased risk of readmission at 30 days (OR 1.04, 95% CI 0.87-1.25, p=0.67) or 90 days (OR 1.06, 95% CI 0.90-1.25, p=0.48) as compared to male sex.

Conclusions:
Sex was not an independent predictor of 30-day and 90-day readmissions after nonelective TEVAR. While males had higher rates of complications such as acute kidney injury and mesenteric ischemia, mortality did not differ significantly between the two groups.
Abstract 12946: Identification of a LMNA Synonymous Variant Associated With Severe Dilated Cardiomyopathy
Authors: Gao Shanshan , Mumme-monheit Abigail , Chen Suet Nee , Slavov Dobromir , Spector Elaine B , Baralle Francisco , Bristow Michael , Mestroni Luisa , Taylor Matthew
Published: April 2022

Dilated cardiomyopathy (DCM) is one of the most common cardiac phenotypes caused by mutations of lamin A/C (LMNA) gene in humans. Almost 50% of LMNA variants reported in ClinVar as pathogenic or likely pathogenic are due to frameshift, nonsense, or splicing variants, predictive of haploinsufficiency for LMNA protein. In contrast, synonymous variants that do not immediately suggest a haploinsufficiency mechanism are much harder to interpret. We evaluated a cohort of 57 patients who underwent heart transplant for dilated cardiomyopathy for LMNA variants and identified a novel synonymous variant c.936G>A in the last nucleotide of exon 5 of LMNA in a DCM family. Clinically, LMNA c.936G>A carriers presented with severe DCM, conduction disease and high creatine-kinase levels. Sanger sequencing showed the presence of LMNA c.936G>A in the genomic DNA but not in the cDNA derived from one family member’s heart tissue. RT-PCR using RNA from the patient’s heart tissue was performed with primers that amplified LMNA exons 4-6. DNA fragments amplified by RT-PCR were then cloned into pcDNAII vector and 40 clones were picked and sequenced. An aberrantly spliced mRNA containing the variant and a premature stop codon was identified in 1 of the 40 clones. Real-time quantitative PCR showed significantly lower LMNA mRNA levels in the patient’s heart compared to the controls. Our findings suggest that the c.936G>A LMNA variant resulted in aberrant RNA splicing, which possibly triggers nonsense-mediated RNA decay, leading to reduced mRNA and likely protein expression. These results expand the understanding on the association between synonymous LMNA variants and the molecular pathogenesis of LMNA-DCM.
Abstract 12950: PUMA Sequestration by IP3Rs Underlies Maladaptive Cardiac Fibrosis
Authors: Gambardella Jessica , Jankauskas Stanislovas , Wang Xujun , Santulli Gaetano
Published: April 2022

Introduction:
Following an ischemic injury, the persistence of cardiac myofibroblast (myo-FBs) contributes to fibrosis and adverse myocardial remodeling, especially if myoFBs remain active in otherwise healthy areas of the heart, away from the site of injury. The exact mechanisms underlying myo-FB activation and persistence remain unknown.

Hypothesis:
Since recent genome-wide association (GWA) studies have identified a significant association between gain-of-function mutations in genes encoding for inositol 1,4,5-trisphosphate receptors (IP3Rs) and ischemic heart disease, we hypothesized that IP3Rs could be involved in post-ischemic cardiac fibrosis.

Methods:
We applied an established model of ischemia/reperfusion (I/R) to a newly generated triple KO mouse specifically lacking all isoforms of IP3Rs in cardiac myo-FBs, in order to avoid compensatory responses.

Results:
After I/R, IP3Rs level is not changed in the scar area, whereas it is markedly upregulated in the remote regions. Compared to control littermates, KO mice display a reduced interstitial fibrosis and an attenuated myocardial dysfunction following I/R.

Mechanistically, we show for the first time that IP3Rs modulate apoptosis in myo-FBs following ischemic injury in a calcium-independent manner,
i.e.
by directly sequestrating the pro-apoptotic factor PUMA (p53 upregulated modulator of apoptosis), thereby favoring the detrimental myoFBs persistence in the remote areas. Strikingly, these results were confirmed in human cardiac specimens from patients with heart failure, as well as
in vitro
in human FBs, in which IP3Rs are shown to regulate cell proliferation and migration.

Conclusions:
Our findings indicate that the IP3R-PUMA interaction selectively regulate the activation of cardiac myo-FBs located in the regions remote from the ischemic injury.
Abstract 12968: mitoTEMPO Improves Expression of Pulmonary Artery Soluble Guanylate Cyclase β1 and Lowers Exercise Associated Elevations in Pulmonary Artery Pressures in a Rat Model of Combined Pre- and Post-Capillary Pulmonary Hypertension
Authors: Triantafyllou Georgios , Satoh Taijyu , MCTIERNAN Charles F , Shiva Sruti , Straub Adam C , Gladwin Mark T
Published: April 2022

Introduction:
Exercise induced pulmonary hypertension (EIPH) portends worse prognosis compared to isolated resting PH. Exercise increases mitochondrial reactive oxygen species (mROS) production in peripheral blood mononuclear cells of patients with heart failure. Metabolic syndrome related mROS contribute to EIPH by decreasing the expression of the vasodilatory enzyme soluble guanylate cyclase (sGC) via downregulating an sGC transcription factor, namely nuclear factor Y alpha (NFYA; Satoh et al in press).

Hypothesis:
mROS scavenging with mitoTEMPO will restore sGC expression and ameliorate EIPH in a rat model of combined pre-and post-capillary pulmonary hypertension (CpcPH).

Methods:
Obese ZSF1 rats treated with sugen were used to model CpcPH. Half received mitoTEMPO (2mM) for 2 weeks. CpcPH rats treated with vehicle and lean ZSF1 rats served as controls (n=6/group). Hemodynamics were evaluated at rest and during treadmill exercise. Cardiac function was assessed using Doppler-echocardiography. We cultured pulmonary artery vascular smooth muscle cells (PAVSMCs) from lean rats in palmitate, glucose and insulin (PGI) containing media to simulate the metabolic syndrome milieu. Cells were treated with vehicle or mitoTEMPO. Expression of sGCβ1 and NFYA in pulmonary arteries of animals and in cultured cells was quantified by Western Blot. Data were analyzed with repeated measures two-way ANOVA.

Results:
MitoTEMPO significantly improved EIPH by reducing pulmonary vascular resistance (fig1A), significantly improved right ventricular function (fig1B) and significantly restored NFYA/sGCβ1 expression in pulmonary arteries (fig1C) and PAVSMCs of rats with CpcPH (fig1D). MitoTEMPO significantly blunted PGI-induced downregulation of NFYA and sGCβ1 in PAVSMCs from lean rats (fig1E).

Conclusions:
Mitochondria targeted antioxidants can improve EIPH in CpcPH by restoring NFYA/sGCβ1 expression, identifying a potential therapeutic target for CpcPH.
Abstract 12986: Association of Gestational Diabetes With Subclinical Cardiovascular Disease on Echocardiogram and Endothelial Function Testing
Authors: Minhas Anum , Countouris Malamo E , Ndumele Chiadi E , Selvin Elizabeth , Vaught Arthur J , Gandley Robin , Hays Allison , Ouyang Pamela , Bennett Wendy L , Catov Janet M , Michos Erin
Published: April 2022

Introduction:
Gestational diabetes mellitus (GDM) increases risk for cardiovascular disease (CVD). The subclinical cardiovascular structural and functional changes that contribute to long-term cardiovascular risk are unclear.

Hypothesis:
We hypothesized that GDM is associated with adverse cardiovascular remodeling, diastolic function abnormalities, and endothelial dysfunction at approximately a decade after delivery, thereby increasing CVD risk.

Methods:
We conducted a cross-sectional analysis of women from an existing cohort with abstracted clinical pregnancy data. Women attended a follow-up visit at a median of 9 years after delivery. Echocardiograms, Peripheral Arterial Tonometry (EndoPAT), glycocalyx analysis (GlycoCheck) and laboratory testing were conducted at the follow-up visit.

Results:
Among 217 women who attended the follow-up visit, 53 (24%) had history of GDM. After adjusting for age, race, preeclampsia history or preterm delivery, women with prior Compared to women without GDM, women with prior GDM had higher interventricular septal and left ventricular (LV) posterior wall thickness and lower septal e’ velocity (
Table
; Model 2). They also had worse endothelial function with lower reactive hyperemia index (RHI) and adverse GlycoCheck parameters. Measures of hypertrophy were attenuated by additional adjustment for body mass index, hypertension, and diabetes (Model 3), but findings of adverse LV diastology, RHI and GlycoCheck parameters remained significant.

Conclusions:
Women with GDM were more likely to have increased LV wall thickness, adverse diastology and endothelial dysfunction nearly a decade postpartum. Adjusting for traditional cardiovascular risk factors attenuated some but not all parameters. These findings suggest that subclinical structural and functional cardiac and vascular changes may be a mechanism by which GDM causes increased risk of CVD.
Abstract 12989: Impact of Vasopressor Use on Brain Edema and Neurological Outcomes Among Resuscitated Cardiac Arrest Survivors
Authors: Dutta Abhishek , Majeed Nasir , McDonald Lawson , Masmoudi Youssef , Azizian John , Qureshi Waqas
Published: April 2022

Introduction:
Current guidelines in post cardiac arrest care recommend the use of vasopressors for hemodynamic optimization. The use of hypothermia can further challenge hemodynamics. The impact of vasopressors among cardiac arrest survivors on neurological outcomes is not well studied

Hypothesis:
We hypothesized that duration and use of vasopressor are not associated with poor neurological outcome and brain edema

Methods:
We enrolled cardiac arrest survivors from January 2012 - December 2016 that were able to survive for 24 hours or more. We examined associations of vasopressor use and duration with brain edema and poor neurological outcomes in adjusted logistic regression models (Fig 1). Poor neurological recovery was defined as cerebral performance score (CPC) of >2 or modified Rankin score of >3(unable to perform daily activities independently).Kaplan-Meier was used to depict relationship of brain edema with mortality.

Results:
Out of 981 cardiac arrest survivors (mean age 62.5±14.8 years, 39.3% female, 70.4% white, 34.7% shockable rhythm), 754 (76.6%) were treated with vasopressors. CT or MRI brain were performed among 931 (94.9%) of the patients and brain edema was present among 445 (47.8%) of the patients. Brian edema was independently associated with mortality (HR 2.50; 95% 2.06 - 3.04, p <0.001). Vasopressor use was significantly associated with brain edema (OR 2.90; 95% CI 2.00 - 4.21, p <0.001). Vasopressor duration was also an independent risk factor of brain edema (OR per hour of vasopressor use 1.031; 95% CI 1.002 - 1.061, p = 0.03). In addition to this, vasopressor use was associated with CPC >2 (OR 1.04; 95% CI 1.01 - 1.07, p = 0.006) and with modified Rankin score >3 (OR 1.04; 95% CI 1.01 - 1.07, p = 0.006).

Conclusions:
We observed that the duration and use of vasopressor were associated with poor neurological outcomes and brain edema among cardiac arrest survivors. Future studies should evaluate the mechanism of brain edema associated with vasopressor use.
Abstract 12991: Staged Hybrid Convergent Procedure for Persistent Atrial Fibrillation: Single Center Outcomes From a Community Hospital
Authors: Lnu Kriti , Udeh Uba C , Loran David B , Patel Chinmay P , Link Michael G , theckumparampil nikhil P
Published: April 2022

Introduction:
Hybrid-Convergent procedure(HCP) has been recently approved for treatment of persistent atrial fibrillation(AF). This was studied as a same day procedure which posed significant scheduling challenges with regards to procedure space and personnel. Staging the procedure was more convenient in smaller and busy Community Hospitals like ours. We report our experience with Staged HCP.

Methods:
We retrospectively analyzed all patients who underwent HCP at our Hospital from January 1,2017 to December 31,2020. Same day HCP were excluded. Outcomes at 6 month and 1 year follow up after the procedure were analyzed.

Results:
A total of 29 patients with persistent AF underwent Staged HCP. The mean age was 62.3 years with 75.86% being men. Periprocedural and 30 day mortality was 0%. The mean time between epicardial ablation and endocardial ablation was 46.15 days (SD :17.5 days, interquartile range 6-78). Freedom from AF (normal sinus rhythm on electrocardiograms and/or <1% AF burden on >24 hour monitoring) was seen in 77.78% and 88% patients at 6 months and 1 year respectively. Success of procedure (freedom from AF with maintenance as before procedure, decrease in dose of or complete cessation of Class I/III anti-arrhythmic drug) was seen in 70.4% and 76% at 6 months and 1 year respectively. The de-escalation in treatment (complete cessation or dose reduction of Class I/III anti-arrhythmic drug) at 6 month and 1 year follow up was seen in 57.14% and in 54.55% patients respectively.

Conclusions:
Staged HCP can be done safely with excellent outcomes on par with results seen in the CONVERGE Clinical Trial
Abstract 12993: Administration of Echogenic Immunoliposome-Targeted CD146
+
Mesenchymal Stem Cells Reduces Hypercholesterolemia and Atherosclerosis
Authors: Geng Yong-jian , Klegerman Melvin E , Gao Song , Shelat Harnath S , McPherson David D
Published: April 2022

Introduction and Hypothesis:
Mesenchymal stem cells (MSC) have been used to treat atherosclerosis and diabetes in animal studies and clinical trials. We developed a nanotechnology in which MSC can be targeted with anti-CD146/ICAM bifunctional (BF) echogenic immunoliposomes (ELIP) for treatment of atherosclerosis. Here, we tested the hypothesis that BF-ELIP targeted MSC therapy is biologically safe and effective for preventing hypercholesterolemia and atheroma.

Methods and Results:
BF-ELIP with antibodies to the mesenchymal marker CD146 and the adhesion protein ICAM-1 were mixed with CD146
+
MSC grown from adipose tissue of green fluorescence protein (GFP)-transgenic mice. The BF-ELIP/MSC mixtures or controls, such as non-immune ELIP (NE)/MSC mixtures, NE and MSC alone, were intravenously administered to C57BL/6J wild type (WT) and apolipoprotein-E deficient (ApoE
-/-
) mice, which were age-/sex-matched. In a nearly 4 months followup, all the mice survived the ELIP/MSC injection without major adverse effects observed. No major difference in blood pressure was found between ELIP/MSC-treated and non-MSC controls. Total cholesterol and glucose were examined in blood samples collected from the animals. ApoE
-/-
mice developed significantly higher cholesterol (p<0.05) but lower glucose (p<0.05) levels than WT mice. The BF-ELIP targeted MSC injection reduced levels of total cholesterol and, to a lesser extent, glucose (p<0.05). Non-invasive ultrasound confirmed enhancement of ELIP echogenicity and imaging of atheroma. Fluorescence microscopy illustrated GFP expression in the MSC mixtures and the arterial wall with atheroma. H&E and Oil-Red O staining showed reduced plaque formation and lipid loading in the arterial wall of ApoE
-/-
but not WT mice with the MSC delivery.

Conclusions:
Administration of BF-ELIP targeted MSCs appears to be a safe, effective procedure, which may mitigate hypercholesterolemia and atherogenesis.
Abstract 13207: Peripartum Cardiomyopathy Clinical Characteristics and In Hospital Mortality: Insights From the National Impatient Sample
Authors: Del Rio-Pertuz Gaspar , Del Cid Fratti Juan Daniel , Morataya Cristina , Argueta-Sosa Erwin E
Published: April 2022

Introduction:
The epidemiology of peripartum cardiomyopathy (PPCM) has been described in various countries, with different outcomes and incidence depending on the race and location studied. Recent reports are limited by small sample sizes, which are not enough to make significant conclusions. The aim of the present study is to use a nationally representative database to evaluate clinical characteristics of patients with PPCM and to compare their intrahospital mortality.

Hypothesis:
We hypothesize that there are no significant racial disparities in hospital mortality in patients with PPCM.

Methods:
Retrospective analysis of the National Inpatient Sample (NIS) from 2016 to 2018. Patients with PPCM were identified using ICD10 codes and were classified by race (White, African American, Hispanic, Asian, Native American, and other race). The primary outcome was intrahospital mortality. A multivariate regression analysis was constructed to adjust for confounders.

Results:
We identified a total of 9,370 patients with PPCM. Of them, 36.4% were classified as White, 42.4% as African American, 10.8% as Hispanic, 3.31% as Asian, 1.01% as Native American, and 2.83% as other race. Diabetes was more common in Native Americans, in comparison with arterial hypertension and chronic kidney disease, which were more common in African Americans (Table 1). Compared to White race, the odds of intrahospital mortality in Asian, Hispanic and African American, did not differ amongst races (Figure 1).

Conclusion:
African Americans continue to have more prevalence of PPCM compared to other races. In this sample, intrahospital mortality did not differ. More studies are needed to evaluate if racial disparities contribute for the observed differences in PPCM prevalence and long term outcomes.
Abstract 13212: Chronic Total Occlusion Racial and Income Inequities by Mortality and Cost: Propensity Score and Machine Learning Augmented Nationally Representative Case-Control Study of 30 Million Hospitalizations
Authors: Agrawal Nikhil , Monlezun Dominique , Grable Cullen , Graham Jordan , Marmagkiolis Konstantinos , Chauhan Siddharth , Hostetter Logan , Cilingiroglu Mehmet , Dhoble Abhijeet , Charitakis Konstantinos , Smalling Richard W , Palaskas Nicolas L , Arain Salman A , Iliescu Cezar
Published: April 2022

Introduction:
We sought to produce the first nationally representative analysis of racial and income inequities by mortality and cost for patients with chronic total occlusion (CTO) of coronary arteries by the presence or absence of active cancer.

Methods:
Propensity score adjusted and backward propagation neural network machine learning augmented multivariable regression among patients with CTO and stratified by race and income was conducted for the above outcomes in this case-control study of the United States’ largest and most current all-payer hospitalized dataset, the 2016 National Inpatient Sample. Regression models were fully adjusted for age, geographic region, anemia, thrombocytopenia, cancer metastases, NIS-calculated mortality risk by Diagnosis Related Group (DRG), and the likelihood of undergoing PCI (in addition to length of stay [LOS] for cost). To produce nationally representative estimates, analyses were also adjusted for the complex survey design.

Results:
Of the 30,195,722 adult hospitalized patients, 1,159,994 (3.84%) underwent PCI (of whom 30,624 [2.64%] were in patients with active cancer), and 120,815 (0.40%) had CTO (of whom 3,068 [2.54%] had active cancer). In multivariable regression among patients with CTO, mortality was comparable across races in both PCI and cancer, but significantly increased among the lowest income quartile for patients with cancer (OR 4.09; 95%CI 1.30-12.80; p=0.016). PCI in Hispanic cancer patients unlike other races had significantly increased costs ($207,218.80; 95%CI 76,799.21-337,738.30; p=0.002) as did the lowest income quartile ($26,327.08; 95%CI 21,123.93-31,530.23; p=0.042) unlike other income groups significantly increased costs.

Conclusions:
This large nationally representative study suggests PCI can safely done in hospitalized patients with CTO and active cancer though its prevalence is far less than in those without cancer despite comparable risk profiles; there also appears to be significant racial and income inequities in both mortality and cost by both race and income.
Abstract 13219: ER-Selective Autophagy Alleviates ER Stress-Mediated Myocardial Injury
Authors: Nakagama Shun , Maejima Yasuhiro , Qintao Fan , Shiheido-Watanabe Yuka , Tamura Natsuko , Sasano Tetsuo
Published: April 2022

Introduction:
Increasing lines of evidence suggest endoplasmic reticulum-selective autophagy (ER-phagy) as a cell-protective pathway to mediate degradation of damaged ER. However, the role of ER-phagy in cardiomyocytes and its molecular mechanisms remain unsolved.

Hypothesis:
Considering that various cardiac loads cause ER stress which contributes to the development of heart failure, we hypothesized that ER-phagy would be a compensatory system for protecting cardiomyocytes against ER stress.

Methods and Results:
To evaluate ER-phagy in cardiomyocytes, we generated lentivirus (LV) and cardiac-specific transgenic mice (Tg-mice) harboring ss-RFP-GFP-KDEL sequence, an ER-phagy reporter possessing an N-terminal ER signal sequence followed by tandem fluorescence sequences and ER retention signal. Fluorescent microscopic analyses and immunoblotting demonstrated that amino acid deprivation of LV-ss-RFP-GFP-KDEL-tranduced H9c2 (tfH9c2) cells markedly elevated the amount of RFP fragments, suggesting that ER-phagy is increased in tfH9c2 cells. 48 hours of food starvation markedly induced ER-phagy in Tg-mice hearts, as well. Treatment with Doxorubicin (Dox), a cardiotoxic compound inducing ER stress, activated ER-phagy in tfH9c2 cells as evidenced by the increase in RFP fragments detected by immunoblotting (Control vs. Dox: 1.0±0.2a.u. vs. 31.6±6.3a.u.; p<0.05). Consistently, treatment with Dox (20 mg/kg) significantly induced ER-phagy in myocardium of Tg-mice compared with those of saline-treated ones (Saline vs. Dox: 1.0±0.05a.u. vs. 2.5±0.2a.u.; p<0.05). qRT-PCR analyses revealed that treatment with Dox enhanced the expression of CCPG1, an ER-phagy receptor, in tfH9c2 cells (Control vs. Dox: 1.0±0.05a.u. vs. 2.1±0.2a.u.; p<0.05). Furthermore, LV-CCPG1 transduction-mediated silencing CCPG1 of tfH9c2 cells resulted in the reduction of ER-phagy activity, accumulation of pro-apoptotic proteins including cleaved caspase 3 and deterioration of cell survival (Cell viability: Control vs. Knockdown: 79.0±3.3% vs. 62.4±2.7%; p<0.05) in response to Dox treatment.

Conclusions:
These results suggest that ER-phagy plays a protective role in cardiomyocytes against Dox toxicity, possibly through CCPG1-mediated signaling.
Abstract 13221: The Biomarker-Based ABC-ACS (Age, Biomarkers, Clinical History) Score Can Predict Major Bleeding Better Than Other Contemporary Scores in Patients on Dual Antiplatelet Therapy After Coronary Revascularization: Results of a Large Derivation and Validation Study
Authors: Batra Gorav , Lindback Johan , Becker Richard C , Harrington Robert A , Held Claes , James Stefan K , Kempf Tibor , Lagerqvist Bo , Lopes Renato D , Tricoci Pierluigi , Mahaffey Kenneth W , Steg Philippe , Storey Robert F , Swahn Eva , Wollert Kai C , Siegbahn Agneta , Wallentin Lars
Published: April 2022

Introduction:
Intense and prolonged antithrombotic treatment after acute coronary syndrome (ACS) reduces ischemia but increases bleeding. Risk prediction tools might help individualize antithrombotic treatment.

Hypothesis:
We have previously developed the ABC (age, biomarkers, clinical history) score for major bleeding in patients with atrial fibrillation. We hypothesized that the ABC score might be adapted for prediction of major bleeding in patients after coronary revascularization for ACS.

Methods:
A risk score was developed in 9,845 patients with ACS undergoing coronary revascularization in the PLATelet inhibition and patient Outcomes (PLATO) trial. Model discrimination and calibration was assessed using Harrell’s c-index and calibrations plots. Validation was performed in two external trial cohorts: Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) and Fragmin and Fast Revascularisation during Instability in Coronary Artery Disease (FRISC II). In addition, the novel score was compared to the PRECISE-DAPT and PARIS bleeding scores.

Results:
The ABC-ACS bleeding score was developed from 7,216 person-years of follow-up and 370 episodes of major bleeding in PLATO. Predictors of major bleeding, in order of relative strength, were age, growth differentiation factor-15 (GDF-15) and hemoglobin concentrations, type of P2Y
12
inhibitor and history of bleeding. The score showed good calibration, yielding c-indices of 0.71 in PLATO, 0.65 in TRACER and 0.70 in FRISC II, and performing better than the PRECISE-DAPT and PARIS scores (figure).

Conclusions:
The ABC-ACS bleeding score was internally and externally validated in three cohorts of patients with ACS and showed good discrimination and calibration. The ABC-ACS bleeding score performed better than other contemporary bleeding scores and might improve the decision-making process about intensity and duration of antithrombotic treatment.
Abstract 13222: Genetic Variants Close to
NKX2-5
and
MYH6
Are Associated With AV Nodal Reentry Tachycardia in First Genome-Wide Association Study
Authors: Andreasen Laura , Ahlberg Gustav , Lundegaard Pia Rengtved , Ægisdottir Hildur , Hartmann Jacob Peter , Paludan-Mueller Christian , Hadji-Turdeghal Katra , Ghouse Jonas , Pehrson Steen , Jensen Henrik , Riahi Sam , Hansen Jim , Sandgaard Niels , Haunso stig , Kanters Jorgen , Ellervik Christina , Bundgaard Henning , Ullum Henrik , Holm Hilma , Arnar David , Svendsen Jesper Hastrup , Olesen Morten
Published: April 2022

Introduction:
AV nodal re-entry tachycardia (AVNRT) is the most common type of paroxysmal supraventricular tachycardia. At present, the underlying etiology of AVNRT is unclear.

Hypothesis:
In a genome-wide association study (GWAS), we aimed to identify common genetic variants associated with AVNRT.

Methods:
We performed a GWAS meta-analysis of Danish patients diagnosed with AVNRT verified by invasive electrophysiological study. An Icelandic population of AVNRT patients was used for replication. We performed conditional analysis by adjusting our analysis for atrial fibrillation (AF) genetics and transcriptome-wide analyses (TWAS) to assess associations between gene expression and AVNRT. Electrophysiological consequences were investigated in CRISPR-Cas9 modified zebrafish.

Results:
A total of 1,515 AVNRT patients and 38,428 controls were available for meta-analysis. Two genetic loci associated with AVNRT; at chromosome 5q35.1, close to the
NKX2-5
gene (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.38-1.58, P = 2.6 х 10
-13
), and at 14q11.2 in the
MYH6
gene (OR 1.26, 95% CI 1.18-1.34, P = 2.3 х 10
-8
). We found similar effect sizes and direction of effect for both loci in the Icelandic AVNRT cohort. Using conditional analyses, we found that these loci were associated with AVNRT independent of AF. Analyses of loss of Nkx2-5 zebrafish showed no difference with regards to electrocardiographic parameters and transmission electron microscopy of atrial tissue compared with wildtype.

Conclusion:
This is, to our knowledge, the first GWAS on AVNRT. We identified two genetic loci that associated with AVNRT.
Abstract 13230: Bone Morphogenetic Protein 10 - A Novel Biomarker of Ischemic Stroke in Patients With Atrial Fibrillation
Authors: Hijazi Ziad , Benz Alexander P , Lindback Johan , Connolly Stuart J , Eikelboom John W , Kastner Peter , Ziegler Andre , Oldgren Jonas , Siegbahn Agneta , Wallentin Lars
Published: April 2022

Background:
Biomarkers specifically related to the atrial tissue might increase the understanding of the pathophysiology and improve risk prediction in atrial fibrillation (AF). Bone morphogenetic protein 10 (BMP10) is a novel biomarker expressed in atrial myocardium. We evaluated the association between BMP10 and the risk of stroke, bleeding, and death in patients with AF not treated with oral anticoagulation.

Methods:
BMP10 was measured in 2,974 plasma samples collected at randomisation in patients with AF randomized to aspirin in two cohorts, the ACTIVE-A (n=951) and AVERROES (n=2023) trials, median follow-up of 3.8 and 1.2 years, respectively. BMP10 was analysed with a prototype Elecsys electrochemiluminescence immunoassay. Associations between BMP10 and outcomes were evaluated by Cox-regression analyses adjusted for clinical characteristics, kidney function, and NT-proBNP.

Results:
Median age was 71 years, 58.1% were men. The median concentration of BMP10 was 2.46 (25
th
-75
th
percentiles, 2.09 - 2.94) ng/L. The variables most strongly associated with higher BMP10 levels were: heart rhythm (AF vs sinus), older age, female sex, lower BMI, and kidney dysfunction. BMP10 was the baseline variable most strongly associated with ischemic stroke during follow-up (Figure). After adjustments, the hazard ratio for ischemic stroke (BMP10 3rd vs 1st quartile) was 1.57 [95%CI 1.08-2.28], p=0.025), and the discriminatory value (c-index) was 0.643 (vs 0.634 of CHA
2
DS
2
-VASc score) and improved the full model from 0.737 to 0.746. BMP10 was not associated with bleeding or death. The results were consistent across both cohorts and irrespective of cardiac rhythm at blood sampling.

Conclusions:
In patients with AF, circulating plasma levels of BMP10 are independently associated with the risk of ischemic stroke but not with bleeding or death. BMP10 has an incremental discriminatory value for the risk of ischemic stroke, and may be a novel specific biomarker in patients with AF.
Abstract 13238: Clinical Utility Of Hs-Tni In Healthy Thai Subjects With Intermediate Cardiovascular Risk
Authors: Pipatpongsopon Piyachat , Vathesatogkit Prin , Vanavanan Somlak , Chittamma Anchalee
Published: April 2022

Introduction:
In European countries, hs-cTnI is approved for risk stratification in general population. Whether this indication can be applied to Thai population is unknown. We test the utility of hs-cTnI as a risk stratification tool for incident cardiovascular disease among Thai subjects with intermediate cardiovascular (CV) risk and without previous cardiovascular disease.

Hypothesis:
Hs-cTnI can be used as a risk stratification tool in Thai subject who has intermediate cardiovascular risk.

Methods:
Data were retrieved from 1,757 subjects who had intermediate CV risk (7.5%-19.9%) and had no known CV disease from the electricity generating authority of Thailand (EGAT) study during the year 2007-2009. High-sensitive Troponin I was tested using the Abbot ARCHITECT i2000 SR system. Hs-cTnI was categorized into low, intermediate and high risk using gendered-specific cut-offs points. Major adverse cardiac event (MACE), defined as a composite of CV death, non-fatal myocardial infarction and non-fatal stroke, was collected and confirmed by medical record until 2017-2019. Survival analysis and net reclassification index (NRI) analysis were performed.

Results:
A total of 1,757 subjects had complete data for analysis. Mean age was 57-year-old, 77% were male. After 10 years, 88 CV event (5%) occurred. Median hs-cTnI was 3 (2.2, 4.1) mg/dL. The event rate was significantly highest in high-risk group of hs-cTnI (14%), followed by intermediate (6.4%) and low risk group (4.3%). Multivariate analysis adjusted for conventional risk factor from Thai CV risk score showed that hs-cTnI is an independent risk factor for MACE (HR 1.02, 95% CI 1.01 to 1.03). For the high-risk group, compared to low risk group, hazard ratio was 3.24, 95% CI 1.73 to 6.07 (p value for trend < 0.001). The addition of hsTnI information to prognostic model yielded an NRI of 0.11 (p-value 0.006).

Conclusions:
In this intermediate CV risk population, elevation of hs-cTnI is not uncommon. Hs-cTnI is an independent risk factor for cardiovascular death, myocardial infarction and stroke. Hs-cTnI significantly improves the reclassification as shown by NRI. Hs-cTnI can be used as a risk stratification tool in Thai subject who has intermediate cardiovascular risk.
Abstract 13253: Prevalence of Preclinical Cardiomyopathy in Patients With Type 2 Diabetes With No Apparent Cardiovascular Involvement
Authors: Rajput Rajesh , Mohan JC , Sawhney JPS , Dalal Jamshed , Sankardas Mullasari , Vasnawala Hardik , Kumar Amit
Published: April 2022

Background:
Hyperglycemia is associated with changes in cardiac structure and function, increased atherosclerosis and diabetic cardiomyopathy (1,2). Currently there is scarcity of robust large scale studies evaluating prevalence of asymptomatic left ventricular dysfunction and/or pre-clinical Heart Failure (HF) in patients with T2DM, particularly in India. Therefore, this study was conducted to determine prevalence of pre-clinical cardiomyopathy in Indian patients with T2DM.

Methodology:
Cross sectional, multi-center study was conducted in India. Institutional ethics committee had approved study protocol. Patients aged ≥ 18 years, T2DM with duration of ≥1 year and willing to provide informed consent were included. Patients with coronary artery or valvular disease, previously diagnosed with HF stage III/IV, chronic kidney disease, peripheral artery disease, arrhythmias, diabetes other than T2DM or currently under treatment with digoxin or loop diuretics were excluded. Two-dimensional echocardiography and natriuretic peptide estimation were conducted.

Results:
This is an interim analysis of 569 patients. Mean HbA1c was 8.3%. Total subjects with LVD were 52% (95% CI 0.48,0.56). Diastolic dysfunction was 20% (95% CI 0.17,0.24) and systolic dysfunction was 42% (95% CI 0.38,0.46) (Table 1). Prevalence of HF according to BNP levels >105 pg/ml was 9% (95% CI 0.07,0.11). Correlation analysis between HbA1c and prevalence of LVD was statistically significant for systolic LVD, while it was not statistically significant for diastolic LVD. Patients in the age group of 51 to 60 were more vulnerable to LVD at 35% (95% CI 0.30,0.41).

Conclusion:
Using suitable echocardiographic indexes and laboratory investigations LVD is detectable in almost half of the T2DM patients and has a direct correlation with older age and HbA1c. Thus, we conclude that HF goes undetected and early intervention to diagnose and treat LVD can improve outcome.
Abstract 13255: Left Ventricular Structure and Function in Patients With Chronic Kidney Disease Assessed by 3D Echocardiography
Authors: Christensen Jacob , Landler Nino E , Olsen Flemming J , Feldt-Rasmussen Bo , Hansen Ditte , Kamper Anne-Lise , Bro Susanne L , christoffersen christina , Soerensen Ida Maria M , Saurbrey Bjergfelt Sasha , Freese Ballegaard Ellen Linnea L , Seidelin Eline , Biering-Sørensen Tor
Published: April 2022

Background:
Cardiovascular disease is the leading cause of mortality amongst patients with chronic kidney disease (CKD). This is the first study using 3-dimensional echocardiography (3DE) to investigate associations between adverse changes of the left ventricle, and different stages of CKD.

Methods:
Participants were recruited from the Copenhagen CKD cohort study and the Herlev-Gentofte CKD cohort study. Patients were stratified according to GFR category (G1+2: eGFR≥60mL/min/1.73m
2
, G3: eGFR = 30-59mL/min/1.73m
2
, and G4+5: eGFR≤29mL/min/1.73m
2
), and according to albuminuria (A1: UACR<30 mg/g, A2: 30-300 mg/g, A3: >300 mg/g). Echocardiograms were analysed for left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), and global strain measures. In adjusted analysis, eGFR groups were adjusted for confounders and albuminuria category, while albuminuria groups were adjusted for confounders and GFR category.

Results:
The study population consisted of 662 outpatients with CKD and 169 controls. Mean age was 57±13 years, and 61% were males. Mean LVEF and global longitudinal strain (GLS) were increasingly impaired across eGFR groups: LVEF = 60.1%, 58.4%, and 57.8% (
p
=0.013), GLS = -16.1%, -14.8%, and -14.6% (
p
<0.0001) for G1+2, G3, and G4+5. LVMi and prevalence of LV hypertrophy increased with albuminuria severity: mean LVMi = 87.9g/m
2
, 88.1g/m
2
, and 92.1g/m
2
(
p
=0.007) from A1-3. Adjusted analysis confirmed reduced LVEF in G3 compared with G1+2, and increased LVMi in A3 compared with A1.

Conclusion:
Increasingly impaired eGFR was associated with adverse changes in LV systolic function, while albuminuria was associated with adverse changes in LV mass assessed by 3DE. Their associations were independent of each other.