bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13408: Tumor Endothelial Marker 1 is Upregulated in Cardiomyocytes and Participates in Cardiac Remodeling After Cardiac Injury
Authors: Li Yi-Heng , Chen Po-Sheng , Feng Wen-Han , Chung Hsing-Chun
Published: May 2021

Background:
Tumor endothelial marker 1 (TEM1), also known as endosialin or CD248, is a transmembrane protein that expresses in mesenchymal lineage-derived cells only during embryogenesis and becomes undetectable in normal tissues after birth. Re-expression of TEM1 is found on activated cells of mesenchymal lineage during pathological conditions, such as stroma cells in cancer, fibroblasts in organ fibrosis and wound healing, indicating its potential role in tissue remodeling and repair. The expression levels and physiological functions of TEM1 in heart are unknown.

Methods and Results:
All data were presented as mean ± standard error. In 2 explanted hearts from patients with heart failure (HF) received heart transplantation, immunofluorescence staining showed TEM1 was highly expressed in cardiomyocytes (CMs) and also in cardiac fibroblasts. In mouse HF models induced by intraperitoneal doxorubicin injection (5 mg/kg/wk for 4 wks) or coronary ligation, immunohistochemistry study showed TEM1 expression in hearts. Western blot showed 1.23±0.02 and 1.56±0.04-fold increase of cardiac TEM1 expression compared to controls, respectively. In vitro studies showed TEM1 expression increased in cultured CMs (H9C2 cells) treated with: (1) mechanical stretch (10% elongation at 60 cycles/min) (0 vs 0.5 vs 1 vs 3 hr, Western blot ratio: 1 vs 1.86±0.20 vs 1.87±0.20 vs 1.21±0.21, p<0.05), (2) doxorubicin (100 nM) (0 vs 0.5 vs 2 vs 4 hr: 1 vs 0.70±0.22 vs 1.75±0.26 vs 1.84±0.24, p<0.05) and (3) hypoxia (1% O2) (0 vs 0.5 vs 2 vs 4 hr: 1 vs 1.70±0.06 vs 1.49±0.22 vs 2.07±0.35, p<0.05). Recombinant TEM1 (rTEM1) promoted proliferation of H9C2 cells (saline vs rTEM1 50 vs 100 vs 250 nM, BrdU absorbance: 1.23±0.03 vs 1.36±0.03 vs 1.37±0.05 vs 1.38±0.02, p<0.05), reduced doxorubicin (1uM)-induced apoptosis (apoptosis ratio: 1 vs 0.89±0.02 vs 0.91±0.01 vs 0.88±0.05, p<0.05), increased cell hypertrophy (cell area ratio: 1 vs 1.11±0.21 vs 1.51±0.18 vs 1.63±0.13, p<0.05) and increased collagen production from CMs (collagen 3 Western blot ratio: 1 vs 1.49±0.15 vs 1.53±0.19 vs 1.29±0.24, p<0.05).

Conclusions:
Our study results indicate that TEM1 is upregulated in CMs after cardiac injury and influences the cell behaviors of CMs that related to cardiac remodeling.
Abstract 13409: Impact of Smoking on Vascular Endothelial Growth Factor D and Mortality in Patients With Suspected or Known Coronary Artery Disease: The ANOX Study
Authors: Wada Hiromichi , suzuki masahiro , Matsuda Morihiro , Ajiro Yoichi , Shinozaki Tsuyoshi , Sakagami Satoru , Yonezawa Kazuya , shimizu masatoshi , FUNADA JUNICHI , Takenaka Takashi , Morita Yukiko , Nakamura Toshihiro , Fujimoto Kazuteru , Matsubara Hiromi , Kato Toru , Unoki Takashi , Takagi Daisuke , Wada Kyohma , Wada Miyaka , Iguchi Moritake , Masunaga Nobutoyo , ISHII MITSURU , Kotani Kazuhiko , Abe Mitsuru , Akao Masaharu , Hasegawa Koji
Published: May 2021

Background:
Smoking is a risk factor for mortality in the general population and in patients with coronary artery disease (CAD). Vascular endothelial growth factor D (VEGF-D) is a secreted glycoprotein that can act as lymphangiogenic and angiogenic growth factors. Recently, we demonstrated that circulating VEGF-D levels are associated with the risk of mortality in patients with suspected or known CAD. However, whether VEGF-D levels differ according to smoking status and whether smoking modifies the relationship between VEGF-D and mortality in those patients are unknown.

Methods:
Using data from a multicenter, prospective cohort of 2418 patients with suspected or known CAD, we assessed the association between smoking status and VEGF-D and the impact of smoking status on the association between VEGF-D levels and the risk of all-cause death. VEGF-D was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study. Patients were followed up over 3 years.

Results:
The mean age (standard deviation [SD]) of the patients was 70.6 (10.4) years; 67.2% were men. Current smokers exhibited significantly higher levels of VEGF-D compared to former smokers and never smokers (median [interquartile range], 343 [214-556], 312 [201-500], 291 [182-485] pg/mL, respectively;
P
=0.006). Stepwise multiple linear regression analysis revealed that the log-transformed VEGF-D level was independently associated with current smoking (
P
=0.002), but not with former smoking. After adjusting for potential clinical confounders, the VEGF-D level was significantly associated with all-cause death in never smokers (hazard ratio per 1-SD increase [HR], 1.31; 95% confidence interval [CI], 1.10-1.55) and in former smokers (HR, 1.22; 95% CI, 1.08-1.37), but not in current smokers (HR, 0.92; 95% CI, 0.65-1.22). Furthermore, VEGF-D provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in former smokers or in current smokers.

Conclusions:
Current smoking was independently associated with higher levels of VEGF-D. The prognostic value of VEGF-D on mortality was most pronounced in never smokers among patients with suspected or known CAD.
Abstract 13432: Left Ventricular External Work as a Marker of Cardiac Functional Recovery and Outcome After Transcatheter Aortic Valve Replacement in Patients With Aortic Stenosis
Authors: Tsujinaga Shingo , Iwano Hiroyuki , Motoi Ko , Chiba Yasuyuki , Ishizaka Suguru , Murayama Michito , Nakabachi Masahiro , Yokoyama Shinobu , Nishino Hisao , Okada Kazunori , Kaga Sanae , Kamiya Kiwamu , Nagai Toshiyuki , Anzai Toshihisa
Published: May 2021

Background:
Prediction of cardiac functional recovery and outcome after transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS) is still challenging. We hypothesized that left ventricular (LV) external work estimated by echocardiography before TAVR would reflect potential myocardial damage and thus could be associated with changes in cardiac function and prognosis after TAVR.

Methods:
Echocardiography was performed in 70 AS patients (83 ± 5 years old) before and after TAVR (1 month and 6 months). LV stroke work index (SWI) was calculated as stroke volume index (SVI) х [mean systemic blood pressure + mean pressure gradient across aortic valve (mPG)] before TAVR as a parameter of LV external work. Patients were divided into reduced and preserved SWI group based on the median value (6106 mmHg · mL/m
2
). Cardiac events were defined as cardiac death or worsening heart failure within 12 months after TAVR.

Results:
Reduced group had lower SVI (40 ± 7 vs 57 ± 8 mL/m
2
), mPG (44 ± 14 vs 57 ± 16 mmHg), and smaller aortic valve area index (0.4 ± 0.1 vs 0.5 ± 0.1 cm
2
/m
2
) than preserved group at baseline (p < 0.05 for all), although LV mass index (LVMI) (116 ± 35 vs 128 ± 30 g/m
2
) and left atrial volume index (LAVI) (56 ± 20 vs 52 ± 17 mL/m
2
) were comparable. LV ejection fraction (EF) (57 ± 13 vs 66 ± 7%) and global longitudinal strain (GLS) (–14.2 ± 4.6 vs –16.6 ± 4.8%) at baseline were significantly lower in reduced group than in preserved one. After TAVR, LVMI and LAVI did not change in reduced group (
Table 1
). In contrast, preserved group showed significant decrease in these parameters. Although LV EF did not change in both groups, GLS was significantly improved only in preserved group but not in reduced group (
Table 1
). Seven patients (10%) experienced cardiovascular events after TAVR and all these belonged reduced group.

Conclusions:
Reduced SWI before TAVR was associated with poor response in cardiac function after TAVR and might be a prognostic marker in AS patients undergoing TAVR.
Abstract 13445: Patterns and Outcomes of Thoracic Organ Transplantation Across Citizenship Status in the United Status
Authors: Sinnenberg Lauren , Machado Sara R , Ostrominski John , Stehlik Josef , Mehra Mandeep R , Vaduganathan Muthiah
Published: May 2021

Introduction:
The volume of solid organ transplantation in the US has increased in recent years. Few data are available characterizing thoracic transplantation patterns and outcomes by citizenship status.

Methods:
Citizenship at the time of transplantation was characterized among thoracic organ transplantation recipients in the US between 2013 and 2018 using United Network for Organ Sharing data. The non-US citizen group included non-US citizen/US residents, non-US citizen/non-US residents who travelled to the US for transplantation, and non-US citizen/non-US residents who travelled to the US for reasons other than transplantation. Cox regression models were constructed to examine the association between citizenship status and death or graft failure, accounting for age, sex, race, and payment method.

Results:
Among 31,174 thoracic organ transplantations, number of non-US citizen thoracic organ recipients increased from 90 in 2013 to 221 in 2018 (a 146% increase). Proportion of non-US citizen recipients (of all recipients) similarly increased from 2.0% in 2013 to 3.7% in 2018 (Figure 1a). Non-US citizens were, on average, younger than US citizens (46±19 vs 51±19 years, p<0.001) and were less likely to be supported by Medicaid (13% vs. 22%, p<0.001). By 6 months, there were 2,228 deaths or graft failures, which similarly occurred among non-US citizens and US-citizens (6.1% vs 6.8%, P=0.38) (Figure 1b). Non-US citizens did not experience higher covariate-adjusted risk of post-transplant death or graft failure compared with US citizens (adj. HR 0.93; 95% CI 0.70-1.25; P=0.64).

Conclusions:
Between 2013 and 2018, there was a modest increase in non-US citizen recipients of thoracic organ transplantation. Non-US citizens have similar risk-adjusted patient and graft survival when undergoing thoracic organ transplantation compared with US citizens.
Abstract 13461: Longitudinal Evolution of Epicardial Pacing Leads
Authors: Racine Hugo Pierre , Philippon Francois , Molin Franck , Sarrazin Jean-François , Nault Isabelle , Plourde Benoit , Roy Karine , Blier Louis , O'Hara Gilles , Jacques Frederic , Champagne Jean , Steinberg Christian
Published: May 2021

Introduction:
Implantation of epicardial pacing leads remains a well-known alternative to the standard transvenous approach in several situations. However, long-term data on the performance and safety of epicardial pacing leads remain scarce.

Methods:
We conducted a retrospective cohort study at a single tertiary center including all patients with right or left ventricular epicardial lead implantation between 1996 to 2018; n=255. Electrophysiological lead parameters at implantation and during follow-up were analyzed and compared with clinical data from the electronic medical records.

Results:
230 patients were included in the analysis. Implanted lead models included the Medtronic
4968
(n=202) and Medtronic
5071
(n=28). Indications for epicardial lead implantation included upgrade to CRT in 153/230 (67%) individuals and standard right or left ventricular pacing only in 76/230 (33%). Of the 153 epicardial CRT patients, 50 had a history of failed transvenous CRT and 103 had concomitant cardiac surgery for other indications and were thought to have a likely indication for CRT in the nearby future. Mean follow-up time was 4,7years±4,2. Lead impedances were significantly higher in the 4968 model compared to the 5071. Pacing thresholds for both lead models were similar at implantation but were subsequently significant higher in the 5071 model. Higher pacing thresholds in the 5071 model did not result in premature battery depletion. Periprocedural complications related to the epicardial lead insertion occurred in 3/230 patients. Epicardial lead related complications at follow-up remained low (8/230; 3 dysfunctions, 2 dislodgments, 1 impending skin erosion). There were only 2 cases of epicardial lead infections at follow-up requiring surgical extraction. 4,3% of all implanted leads remained unconnected at follow-up.

Conclusions:
Epicardial lead implantation for either CRT or pacing indications is a durable and safe alternative to transvenous lead insertion.
Abstract 13466: Gender and Racial Disparities in Clinical Outcomes Among Patients With Preserved Ejection Fraction Heart Failure
Authors: Diala Chiamaka S , Chukwuma Vivian , Lukan Abdulkareem , Sanni Habeeb , Aibangbee Keziah , Fasanmi Oluwafisayo , Eromosele Oseiwe , Ogunsua Adedotun A , Olagoke Olakanmi , Abu Hawa O , Igbinomwanhia Efehi
Published: May 2021

Background:
Heart failure is a chronic cardiovascular condition with associated high morbidity, mortality and health-related costs. The disparities of varying sociodemographic factors associated with clinical outcomes in patients with preserved ejection fraction heart failure (HFpEF) is yet to be extensively studied.

Aim:
To evaluate gender and racial disparities in length of hospital stay (LOS), cost of hospitalization, and in-hospital (IH) mortality in patients with HFpEF.

Method:
Adults (>18 years) with a primary diagnosis of Acute on Chronic Diastolic dysfunction were identified from the 2016 and 2017 National Inpatient Sample using ICD 10 codes. The relationship between gender or racial groups (Non-Hispanic Whites (NHW)-Ref, Non-Hispanic Blacks (NHB), Hispanics, Asian/Pacific Islanders and Native Americans and study clinical outcomes were assessed using weighted multivariable logistic and linear regression models as appropriate.

Results:
Among patients with HFpEF (n=595,936), 59.8% were females; 73.4%, 15.6%, 6.6%, 1.9%, and 2.5% were NHW, NHB, Hispanics, Native Americans, and Asians/Pacific Islanders respectively. Females had lower IH mortality [adjusted OR (aOR) 0.9; 95% CI: 0.87 - 0.92) compared to males. Compared to NHW, NHB (aOR 0.81; 95%CI: 0.77 - 0.84) and Hispanics (aOR 0.91; 95%CI: 0.86 - 0.96) had lower odds of IH mortality, while IH mortality in Asian/Pacific Islander and Native American was not significantly different from NHW. Females had lower LOS (mean difference(mD) -0.34 days; 95%CI -0.38 to -0.30) and lower hospital cost (mD -$1967; 95%CI: -2097 to -1838) than males. NHB had similar rates of LOS (mD 0.04days; 95%CI: -0.02 - 0.11) and hospital cost (mD -$176; 95%CI: -412 - 60) compared to NHW. Hispanics had similar rates of LOS but higher hospital cost (mD 0.07 days; 95%CI -0.04 - 0.18; mD $1182; 95%CI: 754 - 1609), Asians/Pacific Islander (mD 0.32 days; 95%CI: 0.14 - 0.49, mD $2846; 95%CI 2173 - 3519) and Native American had a higher LOS and hospital cost compared to NHW (mD 0.49 days; 95%CI: 0.33 - 0.64, mD $2793; 95%CI: 2048 - 3539).

Conclusion:
Our study highlights racial and gender disparities in important clinical outcomes among patients with HFpEF, buttressing the need to tailor intervention to higher risk groups.
Abstract 13467: Vasodilatation Stress Cardiovascular Magnetic Resonance: Feasibility and Safety in a Monocentric Prospective Study
Authors: Pezel Theo , Garot Philippe , Hovasse Thomas , Unterseeh Thierry , Toupin Solenn , Morice Marie Claude , Champagne Stephane , Louvard Yves , Sanguineti Francesca , Garot Jerome
Published: May 2021

Introduction:
Cardiovascular magnetic resonance imaging (CMR) has emerged as an accurate technique that can assess ventricular function, stress myocardial perfusion, and viability, without radiation. Recent studies have shown that stress CMR would be the best test to predict obstructive coronary artery disease (CAD) with a good safety.

Hypothesis:
To assess the feasibility and incidence of immediate complications of stress CMR in a tertiary Cardiovascular Center with CMR Laboratory dedicated.

Methods:
Prospective registry of vasodilator stress CMR in a French center with CMR expertise included all consecutive patients referred for vasodilator stress perfusion CMR to detect an obstructive CAD between 2008 and 2020. Stress CMR was performed at 1.5 T using dipyridamole. The clinical and demographic data, quality of test, CMR findings, haemodynamic data, and complications were prospectively recorded.

Results:
Stress CMR was performed in 35,157 patients (98.2% of requested). The study could not be performed due to claustrophobia in 0.3%. Quality was optimal in 93.1%, suboptimal in 6.4%, and poor in 0.5% of studies. Images were diagnostic in 97.9% of patients. No patient died or had acute myocardial infarction during the test. Moreover, 56 patients (0.16%) had severe immediate complications, and one anaphylactic shock post-gadolinium. The only factor significantly associated with higher incidence of serious complications was the detection of inducible ischaemia (p<0.001). Incidence of non-severe complications was low (1.5%), severe controlled chest pain being the most frequent. Minor symptoms occurred frequently (35.5%).

Conclusions:
Performance of stress CMR is safe with very high image rate of satisfactory quality to perform the diagnosis in a referral population. Inducible ischaemia was the only factor identified which was associated with serious complications.
Abstract 13475: Stress Perfusion Cardiovascular Magnetic Resonance Provides Strong Long-term Prognostic Value to Cardiac Events Irrespective of Patient Sex
Authors: Pezel Theo , Garot Philippe , Kinnel Marine , Landon Valentin , Hovasse Thomas , Morice Marie Claude , Unterseeh Thierry , Toupin Solenn , Champagne Stephane , Louvard Yves , Sanguineti Francesca , Garot Jerome
Published: May 2021

Introduction:
Compelling evidence indicates that women with coronary artery disease (CAD) experience worse outcomes than men.

Hypothesis:
To test the hypothesis that stress CMR can provide robust prognostic value in women to the same extent as in men.

Methods:
Consecutive patients referred for stress CMR with dipyridamole were followed for the occurrence of major adverse cardiovascular events (MACE): cardiovascular death or non-fatal myocardial infarction (MI). The secondary endpoint was cardiovascular death.

Results:
Of 3436 patients referred for stress CMR in a single French center, 3322 completed the CMR protocol (60±12yrs, 57%men), and among those 3033 (91%) completed the follow-up (median follow-up 5.4±0.2 years). Reasons for failure to complete CMR included renal failure (n=29), claustrophobia (n=26), poor gating (n=22), intolerance to stress agent (n=19) and declining participation (n=18). Stress CMR was well tolerated without occurrence of death or severe disabling adverse event. Using Kaplan-Meier analysis, the presence of myocardial ischemia identified the occurrence of MACE for both women (hazard ratio HR 2.36; 95% CI[1.54-3.62];
p
<0.001) and men (HR 3.57; 95% CI[2.75-4.64];
p
<0.001). Moreover, inducible ischemia was associated with cardiovascular death for both women (HR 1.92; 95% CI[1.12-2.74];
p
=0.04) and men (HR 2.71; 95%CI[1.98-4.41];
p
<0.001). In a multivariable stepwise Cox regression including clinical characteristics and CMR, inducible ischemia was an independent predictor of a higher incidence of MACE for both women (hazard ratio HR 1.85; 95% CI[1.18-2.92];
p
=0.008) and men (HR 3.55; 95% CI[2.73-4.63];
p
<0.001).

Conclusions:
Stress CMR is feasible, safe and has a good discriminative prognostic value to predict the occurrence of MACE and cardiovascular mortality in patients of either sex presenting with inducible ischemia.
Abstract 13483: Predictors of Thirty-day Readmission for Patients Undergoing Left Atrial Appendage Occlusion Device Placement: Insights From the National Readmission Database 2016-2017
Authors: Sami Farhad , Mohammed Moghniuddin , Ranka Sagar , Noheria Amit , Sheldon Seth , Reddy Madhu
Published: May 2021

Introduction:
Watchman device is an alternative for anticoagulation in atrial fibrillation (AF) patients for stroke prevention but there is paucity of data on 30-day readmission trends and factors influencing it.

Methods:
We queried the 2016-2017 National Readmission Database for all adult AF patients, who had procedure done in January to November and discharged alive, using ICD10 code of 02L73DK. We divided the study population into deciles and used the annual procedure volume cut-off of 20 to compare the lowest volume decile with rest of the study population. Hierarchical multivariable logistic regression model was created to identify predictors of 30-day readmission and hospitals were included as random effect.

Results:
A total of 4565 and 9219 procedures were included for 2016 and 2017; respectively. Overall readmission rate was 1287 (9.3%) and of these 43 (3.3%) died on readmission. The 30-day readmission rate in 2017 was 906 (9.8%) compared to 381 (8.4%) in 2016 (p = 0.053) but the mortality associated with readmission was significantly higher in 2017 at 38 (0.42%) compared to 5 (0.11%) in 2016 (p=0.01). The proportion of patients with Charlson co-morbidity index ≥5 was significantly higher in 2017 at 1177 (12.8%) compared to 384 (8.4%) in 2016 (p <0.001). Annual procedure volume was a significant predictor of readmissions even after controlling for sex, co-morbidities and index-hospital complications (Figure 1). Septicemia (25.2%) and GI bleeding (17.9%) were the most common cause of readmission in patients who died and survived readmission; respectively (Figure 2).

Conclusions:
Thirty-day readmission rate and mortality has been increasing along with the procedural volume which could be related to patients with higher number of co-morbidities receiving the device. Lower procedural volume of the hospital is an independent predictor of readmission.
Abstract 13487: Impact of the New Definition of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction
Authors: Sera Fusako , Ohtani Tomohito , nakamoto kei , Hikoso Shungo , Nakatani Daisaku , Tamaki Shunsuke , Yano Masamichi , Hayashi Takaharu , Nakagawa Akito , Nakagawa Yusuke , Yasumura Yoshio , Yamada Takahisa , Yamauchi-Takihara Keiko , Sakata Yasushi
Published: May 2021

Introduction:
The proposed revision of hemodynamic definition of pulmonary hypertension (PH) adopts a lower threshold of mean pulmonary artery pressure (mPAP) > 20 mmHg. In addition, pulmonary vascular resistance (PVR) ≥ 3 Wood units (WU) is included as the definition of pre-capillary component of PH. Heart failure (HF) with preserved ejection fraction (HFpEF) can develop pre-capillary PH as well as post-capillary PH. We aimed to investigate the impact of the proposed definition of PH on clinical diagnosis of PH associated with HFpEF.

Methods:
From the PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) registry, 225 patients who were hospitalized with HF and underwent right heart catheterization were categorized according to the current guidelines and the proposed definition of PH: non-PH, isolated post-capillary PH (Ipc-PH), pre-capillary PH, and combined pre- and post-capillary PH (Cpc-PH). In the proposed definition, patients with mPAP > 20 mmHg, PVR < 3 WU, and pulmonary artery wedge pressure ≤ 15 mmHg do not meet criteria for any of the above categories and are categorized as “unclassified PH”.

Results:
Prevalence of PH was significantly increased in the proposed definition compared to that in the current definition (51% vs 29%, p<0.0001), with a doubled frequency of pre-capillary PH (Fig A). Furthermore, 24 patients (11%) were diagnosed as unclassified PH and accounted for 22% of those with PH by the proposed definition. Among the PH categories in the proposed definition, Cpc-PH category was significantly relevant for worse prognosis at 1 year after discharge in patients with HFpEF (p=0.03 vs non-PH by log-rank test with Bonferroni's correction) (Fig 2).

Conclusions:
The new definition of PH resulted in a remarkable increase of prevalence of PH in HFpEF with a quite a few patients with unclassified PH and doubled frequency of pre-capillary PH.
Abstract 13494: Lncrna Khps1 Regulates Hif-1a-dependent Pulmonary Vascular Remodeling by Targeting Mir-1, Sphk1 and S1pr2
Authors: Bai Yang , Lockett Angelia , Gomes Marta T , Jones Nicole , de Brito Carneiro Alan , Lai Yen Chun , MacHado Roberto F
Published: May 2021

Rationale:
Pulmonary vascular remodeling is common in pulmonary arterial hypertension (PAH) and is associated with increased risk of right ventricular failure and death. We have previously reported that sphingosine kinase 1 (Sphk1), sphingosine 1 phosphate receptor 2 (S1PR2), microRNA-1-3p (miR-1-3p) and hypoxia-inducible factor-1α (HIF-1α) are involved in the regulation of pulmonary vascular remodeling and the development of PAH. Recently, it has been reported that the long noncoding RNA (LncRNA) Khps1 is required for Sphk1 expression and cell proliferation. However, whether Khps1 plays a role in PAH is unclear. Here, we tested the hypothesis that Khps1 has an impact on pulmonary vascular remodeling in PAH by regulating Sphk1/S1PR2/HIF-1α signaling pathway.

Methods and Results:
Using qRT-PCR, our data showed that Khps1 expression levels were up-regulated in pulmonary artery smooth muscle cells (PASMCs) from PAH patients. Increased Khps1 expression levels were also observed in human PASMCs exposed to hypoxia and in lungs obtained from monocrotaline (MCT)-treated rats or hypoxia exposed mice. Luciferase reporter assays showed that Khps1 expression is dependent on E2F1-mediated promoter activation.
In silico analysis
and luciferase reporter assays also suggested that Khps1 can directly bind to miR-1-3p, suggesting that Khps1 functions as a competing endogenous RNA. Similar studies also showed that miR-1-3p regulates expression of Sphk1 and S1PR2 by binding to their 3’UTR regions. Concurrent E2F1 overexpression and khps1 silencing resulted in a decrease in Sphk1 and S1PR2 expression levels, reduced HIF-1α stabilization and suppressed PASMCs proliferation. Finally, over expression of Sphk1 increased HIF-1α and that in turn increased E2F1 expression in human PASMCs.

Conclusion:
These data reveal a novel regulatory loop between E2F1, Khps1, miR-1-3p and Sphk1/S1PR2 in the regulation of PASMC proliferation and pulmonary vascular remodeling in PAH. These data also suggest Khps1 regulates pulmonary vascular remodeling in a HIF-1α-dependent manner through targeting Sphk1 and S1PR2.
Abstract 13512: Sex-related Differences on Valvular Calcifications in Patients With Aortic Stenosis
Authors: Deslandes Marianne , Clisson Marine , Guzzetti Ezequiel , Barriault Alexandra , Salaun Erwan , Clavel Marie Annick
Published: May 2021

Introduction:
It has been shown that women present lower coronary artery (CAC) and aortic valve calcification (AVC) loads while heavier mitral annular calcification (MAC) than men. However, the sex-specific predictors to these cardiac calcifications remain poorly characterized.

Methods:
We conducted a cross-sectional study in patients with at least mild AS (indexed aortic valve area: AVAi < 1.5 cm
2
/m
2
, Peak aortic jet velocity: Vpeak > 2.0 m/s, or Mean gradient: MG >15 mmHg). Doppler-echocardiography and non-contrast multidetector compute tomography were performed within 3 months. Ascending aorta calcification (AAC), AVC, CAC and MAC scores were measured using the Agatston method. Descriptive statistical analyses (t-test, Wilcoxon, univariate and multivariate analysis) were performed.

Results:
We studied 406 patients (71±11 years, 33% women) with AVAi= 0.59±0.21 cm
2
/cm
2
, Vpeak= 3.1±9.8 m/s, MG= 24.7±17.8 mmHg (equivalent between men and women, all p>0.34). Women present less AVC (480[222-1191] vs 1005[485-2364]AU; p<0.0001), and CAC (366[50-914] vs 626[167-1354]AU; p=0.006), but more MAC (60[1-887] vs 48[0-363]AU; p=0.05) and AAC (227[43-863] vs 142[7-493]AU; p=0.03) than men. Even after comprehensive adjustment, sex remained an independent predictor of each cardiac calcification (all p<0.01). In multivariate analysis, correlates with higher AVC or higher MAC were sex dependent (cf. table). Collinearity was avoided with all variance inflating factor <2.5.

Conclusion:
In AS patients, sex is a powerful and independent predictor of cardiac calcifications. Moreover, predictors of valvular calcification appear to be sex specific.
Abstract 13513: Serial CT Surveillance of Abdominal Aortic Aneurysm Diameter Demonstrates Predominantly Linear Growth (N-TA
3
CT)
Authors: Olson Sydney , Wijesinha Marniker , Panthofer Annalise , Blackwelder William , Upchurch Gilbert R , Terrin Michael , Curci John A , Baxter Timothy T , Matsumura Jon
Published: May 2021

Objective:
Small abdominal aortic aneurysms (AAAs) have a low risk of rupture. Intervention is indicated when diameters exceed established thresholds. This study assessed the growth rates and patterns of AAAs over 2 years as documented on serial CT scans from the Non-Invasive Treatment of AAA Clinical Trial.

Methods:
254 patients, 35 females with baseline AAA maximum transverse diameter (MTD) between 3.5-4.5 cm and 219 males with baseline MTD 3.5-5.0 cm, were included in this study. Linear regressions and segmental growth rates were used to model growth rates and patterns.

Results:
The yearly growth rates of AAA MTDs had a median of 0.17 cm/yr and mean of 0.19 cm/yr ± 0.14 (Figure 1). 10% of AAA displayed minimal to no growth (< 0.05 cm/yr), 62% low growth (0.05-0.25 cm/yr), 28% high growth (> 0.25 cm/yr). Baseline AAA diameter accounted for only 5.4% of growth rate variance (P<0.001, R
2
0.05). Most AAAs displayed linear growth (70%); large variations in interval growth rates occurred infrequently (3% staccato growth, 4% exponential growth); a minority of subjects’ growth patterns were not clearly classifiable (11% indeterminate-not growing, 12% indeterminate-growing) (Figure 2). No patients with baseline MTD < 4.25 cm exceeded sex-specific repair thresholds (males 0 / 92, [95% CI, 0.00-0.06]; females 0 / 25 [95% CI, 0.00-0.25]) in the course of follow-up for as long as two years.

Conclusions:
The majority of small AAAs exhibit linear growth; large intra-patient growth rate variations were infrequently observed over 2 years. AAA < 4.25 cm can be followed with a CT scan in 2 years with little chance of exceeding interventional MTD thresholds of 5.5 cm for men.
Abstract 13523: Self-guided Mobilization in the Cardiac ICU During the COVID Era
Authors: Semsar-kazerooni Koorosh , Goldfarb Michael
Published: May 2021

Introduction:
Measures instituted to prevent the spread of COVID may have an impact on cardiac ICU care practices, such as early mobility (EM) program delivery. A structured EM program was in place in our cardiac ICU prior to COVID. Restrictions on hallway ambulation and patient-provider interaction due to COID led us to modify our EM program to a nurse-assisted, patient-guided program. To our knowledge, there are no studies evaluating patient-guided mobilization in a critical care setting. Thus, our objective was to assess whether self-guided EM was safe and feasible in the cardiac ICU during the COVID period.

Methods:
We reviewed consecutive records in a tertiary care cardiac ICU over a 2-month period following initiation of the self-guided EM program. Only patients who were COVID negative or presumed negative were admitted to the cardiac ICU. Nurses assessed patients using the Level of Function Mobility Score (range 0 to 5, with higher scores indicating better mobility) and provided the current functional level to patients. Patients used their own smartphones or supplied tablets to view video modules, which guided performance of level-specific mobility activities. Patients with contraindications to mobilization based on prespecified criteria were not mobilized. There were 2 mobilization opportunities per day and 3 activities per opportunity.

Results:
There were 52 patients admitted to the CICU during the study period (mean age 67.4 ± 16.0 years; 38.5% female). Ten patients (19.2%) had contraindications to mobilization during unit stay; all of these patients were subsequently mobilized. Two-thirds (66.7%; 208/312) of mobilization opportunities had at least one mobility activity. 72.2% (676/936) of prescribed mobility activities were performed. The adverse event rate was 0.6% (4 events/676 activities); none of these were major or life-threatening. There were no falls or line dislodgements.

Conclusions:
Patient self-guided mobilization was safe and feasible during a period of limited provider-patient interaction in a cardiac ICU. Self-guided EM programs can be considered during periods of restrictions on usual mobility programs. Further studies are needed to evaluate EM in other settings, such as in COVID hospital wards.
Abstract 13526: Global and National Atrial Fibrillation Quality of Care, From 1990 to 2017: Results From the GBD Study
Authors: Shabani Mahsima , Saeedi Moghaddam Sahar , Aminorroaya Arya , Ghasemi Erfan , Rezaei Nazila , Rezaei Negar , Farzadfar Farshad
Published: May 2021

Introduction:
Afib has a drastically higher incidence and burden among elderly. Aside from cardio and cerebrovascular outcomes in these patients, Afib individually brings about a significant mortality among elderly. Scoring systems like CHA2DS2-VASc imply that female gender, advanced age, and comorbidities augment the morbidity of Afib.

Hypothesis:
This study aims to evaluate the global and national discrepancies in Afib quality of care (QoC) within a 38-year time among over 70-year-old population.

Methods:
Four key epidemiologic indices were measured using the data from the estimates of ‘Global Burden of Diseases’ study, 2017: Mortality to incidence, DALY to prevalence, YLL to YLD, and Prevalence to Incidence ratio. Principal Component Analysis was utilized to find the highest value of all eigenvectors of the 4 estimates. The adaptive component derived from this analysis was set as the QoC index (QCI), a centile-based score reflecting better QoC with inclining values. Statistical analyses were done by R software v3.6.1.

Results:
QCI score decreased globally in over 70-year-old population of both females (-4.61%), and males (-3.92%). The gender disparity increased in favor of higher scores for males (-0.50 in 1990, -1.19 in 2017). At the country level, majority of nations had decreased QCI within this period (Figure 1). The US had the second highest QCI in over 70-year-old population (98.30), as well as 80-84 (98.24) and 85-89 years (98.07), specifically. Although the QCI dropped 2.18 scores from 1990 to 2017, the female-male disparity decreased in age group of over 70 (4.15 to 3.44) in US.

Conclusions:
Predominant world-wide decline in QCI, could imply the decreased quality of care for patients with Afib. Observed gender-specific discrepancy in a disease with female-dominant morbidity calls for the necessity to adapt health policies accordingly. However, further studies with adjustment for concomitant risk factors are required to address the underlying causes.
Abstract 13530: A Novel Risk Model to Predict Emergency Department Associated Mortality for Patients Supported With a Ventricular Assist Device: The Ed-vad Risk Score
Authors: Edelson Jonathan B , Edwards Jonathan J , Katcoff Hannah , Mondal Antara , Chen Feiyan , Reza Nosheen , Hanff Thomas C , Griffis Heather M , Mazurek Jeremy A , Wald joyce , Burstein Danielle , Alturi Pavan , O'Connor Matthew J , Wittlieb-Weber Carol , Goldberg Lee R , Zamani Payman , Groeneveld Peter W , Rossano Joseph W , Lin Kimberly Y , Birati Edo
Published: May 2021

Introduction:
The past decade has seen tremendous growth in ambulatory ventricular assist device (VAD) patients. We sought to identify patients that present to the emergency department (ED) who are at the highest risk of death.

Methods:
We performed a retrospective analysis of ED encounters of VAD patients using data from the Nationwide Emergency Department Sample (NEDS) from 2010-2017. Demographic and clinical variables significantly associated with mortality (p < 0.2) in a univariate analysis were evaluated in a multivariate model. Using a random sampling of patient encounters, 80% were assigned to development and 20% to validation cohorts. A risk model was derived from independent predictors of mortality, which were weighted using integer-normalized beta coefficients. Each patient encounter was assigned to one of three groups based on risk score.

Results:
A total of 44,042 ED encounters of VAD patients were included in the study. The majority of patients were male (73.6%), <65 years old (60.1%), and 29% presented with bleeding, ischemic/hemorrhagic stroke, or device complication. Independent predictors of mortality during the ED visit or subsequent admission included age ≥65 years (OR 1.8, 95% CI 1.3, 4.6), primary diagnoses [stroke (OR 19.4, 95% CI 13.1, 28.8), device complication (OR 10.1, 95% CI 6.5, 16.7), cardiac (OR 4.0 95% CI 2.7, 6.1), infection (OR 5.8, 95% CI 3.5, 8.9)], and blood transfusion (OR 2.6, 95% CI 1.8, 4.0), while history of hypertension was protective (OR 0.69, 95% CI 0.5, 0.9)]. The risk score predicted mortality with an area under the curve of 0.78 and 0.71 for development and validation, respectively. Encounters in the highest risk score strata tertile had a 16-fold higher mortality compared to lowest risk tertile (15.8% vs 1.0%).

Conclusions:
We present a novel risk score and its validation for predicting mortality of VAD patients who present to the ED, which can serve as useful tool for clinicians caring for this high-risk, and growing, population.
Abstract 13533: Acute Post-operative Renal Failure and Mortality Risk Following Norwood Surgical Palliation: A Secondary Analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Use Database
Authors: Chamberlain Reid C , Andersen Nicholas D , McCrary Andrew W , Hornik Christoph P , Hill Kevin D
Published: May 2021

Introduction:
The Single Ventricle Reconstruction (SVR) trial randomized neonates with a single morphologic right ventricle undergoing Norwood to a modified Blalock-Taussig shunt (mBTS) or a right ventricle-to-pulmonary artery shunt at 15 centers. The trial demonstrated increased risk of death or heart transplant at one-year post-Norwood in subjects randomized to a mBTS. Using SVR public data, we evaluated incidence and risk factors for post-op renal failure after Norwood, and evaluated the relationship between renal failure, shunt type and one-year post-Norwood mortality.

Methods:
Post-op renal failure was defined
a-priori
as a 3-fold rise in creatinine from baseline, or dialysis use within 7 days of Norwood. We used multivariate logistic regression to evaluate risk factors for post-op renal failure and Cox hazard regression to determine the association between post-op renal failure and one-year post-Norwood mortality.

Results:
Overall 46/544 (8.4%) SVR trial subjects developed post-op renal failure, the majority (32/46, 69.6%) by post-op day 3. In multivariate analysis, risk factors for post-op renal failure included receipt of a mBTS (aOR 3.3, p=0.02), center volume <15 cases/year (aOR 2.7, p=0.005), presence of ≥ 2 pre-op complications (aOR 4.0, p<0.001), low birth weight (aOR 3.2, p=0.002), post-op heart block (aOR 8.5, p=0.001), and delayed sternal closure (aOR 5.3, p=0.026). Renal failure was an independent risk factor for one-year post-Norwood mortality (aHR 1.9, CI 1.1-3.2, p=0.019). When renal failure and shunt type were included as model covariates, there was interaction (p=0.049) with renal failure attenuating the mortality risk associated with receipt of a mBTS (p=0.24), Figure.

Conclusions:
In the SVR trial, post-op renal failure was relatively common but with modifiable risk factors including receipt of a mBTS. Our findings suggest that post-op renal failure accounts for some of the increased mortality risk associated with the mBTS.
Abstract 13562:
COQ8B
: A Candidate Genetic Modifier of Thoracic Aortic Aneurysm Severity
Authors: Landis Benjamin J , Lai Dongbing , Guo Dongchuan , Corvera Joel S , Needler Gavin U , Vujakovich Courtney E , Milewicz Dianna M , Hinton Robert B , Ware Stephanie M
Published: May 2021

Thoracic aortic aneurysm (TAA) is a latent aortopathy that predisposes to life-threatening aortic dissection. Personalized prediction of the risk for progressive aortic dilation and dissection is currently limited. The identification of genetic modifiers may facilitate more precise risk prediction and optimize clinical decisions. We previously identified
COQ8B
, a gene important for mitochondrial biosynthesis of coenzyme Q, as a candidate modifier of TAA severity. Biological evidence for a mitochondrial role in TAA pathogenesis includes severe mitochondrial ultrastructural defects in aortic smooth muscle cells (SMCs) and nitrated tyrosine residues in TAA tissues consistent with oxidative stress. In this study, we hypothesized that a common single nucleotide polymorphism (SNP) rs3865452 in
COQ8B
(c.521A>G, p.H174R) modifies the rate of aortic root dilation. Forty-eight patients with TAA and a mean age at first echocardiogram of 10 ± 5 years were genotyped for rs3865452. Echocardiograms (mean 6.8 ± 4.0 per patient) were performed clinically over a mean interval of 5.3 ± 4.1 years. In mixed model analysis of longitudinal aortic root Z-scores, the c.521G allele was associated with a decreased rate of aortic root dilation in univariate analysis (p=0.0003) and multivariate analysis (p=0.03) that included sex and genetic syndrome as covariates. Hypothesizing a modifier role for
COQ8B
, we analyzed a separate cohort of 230 individuals with early onset thoracic aortic dissection. The c.521G allele was less frequent in dissection cases than controls (p=0.04), also consistent with a protective effect for this SNP. To better understand the mechanism of
COQ8B
effect in TAA, RNA levels of
COQ8B
in SMCs cultured directly from the aorta were assayed, demonstrating levels 2-fold lower in TAA compared with controls. siRNA knockdown of
COQ8B
in aortic SMCS resulted in decreased mitochondrial respiration, increased lipid peroxidation, and altered expression of SMC contractile genes. In conclusion, the findings of this study support a modifier role for the rs3865452 SNP in
COQ8B
in TAA, which may involve mitochondrial pathology and oxidative stress. This suggests that this SNP may be useful for clinical risk prediction.
Abstract 13565: Superoxide Dismutase-loaded Nanoparticles Attenuate Myocardial Ischemia-Reperfusion Injury and Protect Against Chronic Adverse Ventricular Remodeling
Authors: Altshuler Peter J , Cheng Zhiliang J , Schiazza Alexis R , Helmers Mark R , Hu Robin , Chung Jennifer J , Kim Samuel , Jarmula Jakub , Andrew Tsourkas , Atluri Pavan
Published: May 2021

Introduction:
Revascularization relieves myocardial ischemia but induces additional reperfusion injury by oxidative stress. Superoxide dismutase (SOD) is a potent antioxidant with preclinical promise in reducing reperfusion injury but is not well retained within the myocardium.

Hypothesis:
Use of SOD-encapsulated nanoparticles (NP-SOD) will improve SOD retention and preserve cardiac function in a rat model of myocardial ischemia-reperfusion (I/R) injury.

Methods:
Ischemia was maintained for 60 minutes via occlusion of the left anterior descending artery (LAD). Immediately prior to reperfusion, intramyocardial injections of NP-SOD, free SOD or phosphate buffered saline (PBS) were administered along the border of ischemic myocardium. Acute injury was assessed 3 hours post-reperfusion (n=8 per group), and chronic injury at 4 weeks (n=12). Hemodynamics were measured by echocardiography and pressure-volume loops. Acute and chronic injury were examined histologically. Protein isolates at 3 hours measured mediators of cell-death. Intramyocardial enzyme retention analysis was performed by injecting NP or free fluorescent-tagged SOD and explanting hearts for imaging at 0, 24 and 72 hours (n=4 per group).

Results:
Intramyocardial SOD retention was 25% greater in NP-SOD than free SOD at 24 hours (p<0.01) and 78% greater at 72 hours (p<0.01). NP-SOD exhibited improved ventricular function by ejection fraction at 4 weeks (64%) compared to free SOD (51%; p<0.01) and PBS (43%; p<0.01). Cardiac output, stroke volume and end-systolic elastance were greater in NP-SOD. Histology at 28 days demonstrated 54% less macroscopic fibrosis and 85% less microscopic collagen deposition in NP-SOD compared to PBS, and 33/79% compared to free SOD (all p<0.05). Quantifying RIPK3 protein levels in ‘at risk’ myocardium at 3 hours demonstrated 2.5-fold reduced upstream necrosome activation.

Conclusions:
NP-SOD provides prolonged enzyme retention within the myocardium. Intramyocardial NP-SOD administration prior to reperfusion attenuates acute myocardial injury and protects against chronic adverse ventricular remodeling. SOD acts by downregulating necrosis. These findings suggest potential for NP-SOD based therapy in mitigating myocardial I/R injury.
Abstract 13566: Clinical Utility of Noninvasive Assessment of Flow-pressure Relationship in Scleroderma
Authors: Arase Miharu , Kusunose Kenya , morita sae , Yamaguchi Natsumi , Hirata Yukina , Nishio Susumu , Ise Takayuki , Yamaguchi Koji , Fukuda Daiju , Yagi Shusuke , Yamada Hirotsugu , Soeki Takeshi , Wakatsuki Tetsuzo , Sata Masataka
Published: May 2021

Introduction:
Cardiac involvement in Systemic sclerosis (SSc), especially left ventricular diastolic dysfunction (DD), is high prevalence and associated with high mortality. Thus, the early detection of left ventricular DD might be important to manage SSc. Recent study has shown that exercise stress test may evaluate an early stage of heart failure in patients with normal resting echocardiogram.

Hypothesis:
We hypothesized that SSc patients with normal resting hemodynamics may present early phase of left ventricular DD by exercise echocardiogram, leading to the model of predicting long-term outcomes.

Methods:
Between January 2014 and December 2018, we prospectively enrolled 140 SSc patients who underwent 6-minute walk (6MW) stress echocardiographic studies with normal range of estimated mean pulmonary arterial pressure (mPAP) (<25mmHg) and mean pulmonary artery wedge pressure (mPAWP) (<15mmHg) at rest. We used ΔmPAP/Δcardiac output (CO) to assess pulmonary vascular reserve and ΔmPAWP/ΔCO to assess left ventricular (LV) reserve between resting and post-6MW point.

Results:
During a median period of 3.6 years, 25 patients (18%) reached the composite outcome. Both ΔmPAP/ΔCO and ΔmPAWP/ΔCO in patients with events were significantly higher than in ones without events (8.9±3.8mmHg/l/min vs. 3.0±1.7mmHg/l/min; p=0.002, and 2.2±0.9mmHg/l/min vs. 0.9±0.5mmHg/l/min; p<0.001, respectively). In addition, ΔmPAWP/ΔCO is strongly associated with events (p=0.04) in patients with normal ΔmPAP/ΔCO (≤median value), although ΔmPAWP/ΔCO had weak impact in patients with abnormal ΔmPAP/ΔCO (>median value) (p=0.23).

Conclusions:
Exercise echocardiography revealed impaired LV functional reserve in SSc patients with normal resting hemodynamics. Furthermore, in the group of normal pulmonary vascular function, the patients with impaired LV functional reserve had significantly shorter event-free survival than the ones with non-impaired LV function. Thus, the evaluation of early left ventricular DD with 6MW may detect high-risk group in SSc patients.