bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockdown of lncRNA ENST00000603829 Inhibits the Proliferation and Invasion of Salivary Gland Pleomorphic Adenoma through Regulating Cyclin D1
Authors: Xu Yi , Sun Xin , Chen Jing , Xu Jinbiao , Wei Junshui
Published: April 2022

Objective. Salivary gland pleomorphic adenoma (SPA) is a benign neoplasm that can still recur even after radical surgery. To investigate its underlying pathogenesis, here, we examined the significance of lncRNA ENST00000603829 in the proliferation and invasion of SPA. Methods. SPA tissues (

n
=
30

) and adjacent normal tissues (NC;

n
=
30

) were collected from SPA patients treated at our hospital from June 2017 to December 2019. The human normal salivary gland epithelial cell line (HSG) and SPA cells (PA30, PA37, and PA116) were cultured. qRT-PCR was used for detecting the expression of cyclin D1 and lncRNA ENST00000603829 in tissues and cells. lncRNA ENST00000603829/cyclin D1 was knocked down or overexpressed in PA116 cells. The expression of cyclin D1 and lncRNA ENST00000603829 in different cell lines was examined using qRT-PCR. Transwell assays and cell counting kit-8 (CCK-8) were used to assess cellular invasion and proliferation. The testing result regarding the apoptosis rate and cell cycle was obtained via flow cytometry. Western blot provided the measurement of cyclin D1 expression in cells. Results. We observed an upregulation of lncRNA ENST00000603829 and cyclin D1 expression in SPA tissues and cells. Knockdown of lncRNA ENST00000603829 inhibited cell invasion and proliferation, promoting apoptosis and retaining the cells during the G0/G1 phase. However, such effects of lncRNA ENST00000603829 knockdown were inhibited when cyclin D1 was overexpressed. Conclusion. lncRNA ENST00000603829 can promote the occurrence and development of SPA through increasing cyclin D1 expression.
Software Enterprise Risk Detection Model Based on BP Neural Network
Authors: Shan Jiahao , Wang Hongling
Published: April 2022

With the rapid development of software industry, software enterprises have many problems in risk management, and enterprises are facing a huge crisis. In order to detect the risk of software enterprise, a risk detection model based on BP neural network is proposed in this paper. Firstly, risk analysis and modeling are carried out for the software life cycle process of the enterprise. Then, BP neural network is combined with common software risk items to realize supervised deep learning based on label information in data set. Using the advantage of neural network in automatic selection of original data features, the relationship between these risk items is extracted. Meanwhile, the network model in this paper learns the complex relational rules of the input risk features, to classify the risks. Finally, the proposed combined prediction model is compared with other prediction models. The experimental results show that the risk prediction effect of the proposed algorithm is better, to avoid the loss caused by the risk of software enterprises.
Biomarker Development: Bedside to Bench
Authors: Mishkin Grace E. , Kohn Elise C.
Published: April 2022

This commentary complements the report from Nixon and colleagues by addressing the critical definitions, assay and analytical quality control and interpretation, and resources available to advance similar fit-for-purpose biomarker development.

See related articles by Nixon et al., p. 2771 and 2779
Productos defectuosos y alimentos nocivos: reflexiones a partir del Covid-19, con especial referencia al ordenamiento jurídico Chileno
Authors: Soto Erika Isler
Published: April 2022

El presente trabajo tuve por objeto analizar las consecuencias jurídicas derivadas de un alimento nocivo, con una particular referencia a aquella situación que se presenta cuando se fabrique y distribuya en medio de la pandemia y en el ordenamiento jurídico chileno. Para lograr lo anterior, se divide el texto en cuatro partes: vinculación entre seguridad en el consumo y seguridad alimentaria; aproximación al concepto de alimento; aproximación al alimento nocivo; responsabilidad surgida de la fabricación y distribución de alimentos nocivos en medio de la pandemia. A partir de la investigación, se arribó a la conclusión de que un mismo ilícito puede agravarse si se verifica en el contexto de la emergencia sanitaria.
A invenção do leitor
Authors: Mattos Franklin de
Published: April 2022

Aula inaugural que apresenta aspectos do livro O leitor Quixotesco (Título provisório) a ser lançado em 2022.
A vida como repetição da morte: Freud à luz de Deleuze e Foucault
Authors: Noto Carolina
Published: April 2022

Diante das dificuldades do dualismo pulsional de Freud, o presente artigo levanta a hipótese de que seria possível compreender a diferença entre pulsão de vida e pulsão de morte em termos de empírico e transcendental. Essas categorias permitiriam pensar que o organismo, e em particular o aparelho psíquico, tem duas funções que poderiam ser, metodologicamente, diferenciadas: uma função transcendental de destruição e uma função empírica de construção.
Against the Individual. Who qualifies as “one”?
Authors: Zaharijević Adriana
Published: April 2022

The aim of this paper is to focus specifically on the description of the homo politicus as a sovereign individual who governs itself. Searching to understanding of neoliberalism as a governing rationality through which everything becomes economized.
Abstract 12005: Increased Risk of Cancer Therapy-Related Cardiomyopathy in Patients With Treated Immune Checkpoint Inhibitors and Concomitant Cardiotoxic Agents
Authors: lee seonhwa , Cho Iksung , You Seng Chan , Cha Min Jae , Jang Jee suk , Kim William , Go Kyu-yong , Kim Dae-Young , Seo Jiwon , Shim Chi Y , Hong Geu-Ru , Ha Jong-Won , Kim Hyo-song
Published: April 2022

Introduction:
There is scarce data on whether immune checkpoint inhibitor (ICI) increase the risk of cardiomyopathy, especially when used with cardiotoxic agents.

Hypothesis:
We evaluated the cardiotoxicity of the ICI in sarcoma patients receiving doxorubicin with or without ICI by echocardiographic parameters and left ventricular global longitudinal strain (LVGLS).

Methods:
A total of 89 patients were included. Echocardiography and LVGLS were evaluated at baseline and follow-up (after 3 and 6months) and compared between the doxorubicin (n=67) and concomitant ICI with doxorubicin (n=22) groups. Cancer-therapy related cardiac dysfunction (CTRCD) was defined as LVEF drop of >10% and LVEF of <50% (definite CTRCD) and LVEF drop of >10%, LVEF of > 50% and LVGLS relative reduction of >15% (probable CTRCD) at 6months.

Results:
There was no significant difference in age, cumulative dose of doxorubicin and cardiovascular risk factors between two groups. At baseline, LVEF was similar between two groups (p=0.493). In doxorubicin group, LVEF decreased to 59±6 % (p<0.001) and LVGLS decreased from -16.5±3.2 to -14.6±3.2 % (p<0.001) at 6-month. In concomitant ICI and doxorubicin group, LVEF decreased to 55±9 % (p<0.001), along with significantly decreasing LVGLS (-18.6±1.9 to -15.3±3.6 %, p<0.001). Over a median follow-up of 192 days, there were no cases with clinical manifestation of myocarditis. In doxorubicin group, definite and probable CTRCD were 7 (10.1%) and 5 (7.4%) patients, respectively. In concomitant ICI and doxorubicin group, definite and probable CTRCD were 4 (19%) and 4 (19%) patients, respectively. Total CTRCD occurred significantly more in concomitant ICI and doxorubicin than doxorubicin group (38.1% vs. 17.4%, p=0.042).

Conclusions:
ICI increases risk of CTRCD, when concomitantly treated with cardiotoxic agents. Thus, cardiomyopathy should be monitored in patients with ICI by comprehensive echocardiographic assessment including myocardial strain.
Abstract 12007: RNA Sequencing Analysis Reveals A Novel Pathway Associated With The Exacerbation Of Covid-19
Authors: Ikemachi Mami , Miyagawa Kazuya
Published: April 2022

Introduction:
The severity of Coronavirus disease 2019 (COVID-19) depends on the host immune cell response and dysregulation. Most COVID-19 patients had mild disease, however, 15-30 % of patients developed severe disease which could result in severe acute respiratory failure and death. Risk factors associated with severe disease such as age, smoking and comorbidities are well known, while molecular signatures to predict the disease progression are still emerging.

Hypothesis:
Severe COVID-19 have a unique gene expression profile in peripheral blood mononuclear cells (PBMCs) at early stage of disease compared to mild disease.

Methods:
We used RNA sequencing analysis and pathway analysis in PBMCs collected from COVID-19 patients at a median 4 days after the onset. Subsequent clinical course was evaluated by WHO definition (meet any of oxygen saturation < 90 %, respiratory rate > 30 breaths / min and signs of severe respiratory distress or not), and based on the severity, PBMCs obtained from mild (n=6) and severe (n=6) groups were analyzed.

Results:
At the sample collection, there was no significant difference in clinical characteristics between groups, but laboratory tests exhibited higher C-reactive protein and lactate dehydrogenase levels in severe group compared to mild group (Table). We identified 148 differentially expressed genes (DEGs, FDR < 0.05) that are enriched for a pathway, HDACs deacetylate histone, as the top pathway using Metascape. This includes 15 genes in
HIST1
cluster that has not only antimicrobial but also cytotoxic and blood coagulation effect once the proteins are released into circulation, which could result in acute lung injury.

Conclusions:
Our results suggest that the upregulation of
HIST1
cluster genes expression in PBMCs at early stage of COVID-19 could predict the subsequent disease exacerbation. These findings may also link to the pathophysiology of COVID-19 in the context of histone protein mediated lung injury and respiratory failure.
Abstract 12008: Quantitative Pupillometry for Neuroprognostication in Post-Cardiac Arrest: A Prospective Validation Study
Authors: Nyholm Benjamin C , Obling Laust , Grand Johannes , Hassager Christian , Moller Jacob , Othman Marwan , Kondziella Daniel , Kjaergaard Jesper
Published: April 2022

Background:
Quantitative pupillometry is a new tool in multimodal neuroprognostication of comatose patients after out-of-hospital cardiac arrest, but the reliability and precision of quantitative pupillometry is not fully understood.

Methods:
We conducted a prospective blinded validation study with repeated patient assessment at our cardiac intensive care unit. To investigate intra- and interobserver variability of pupil size (mm), each assessment was performed on the same patient by two staff nurses within 2 minutes. The sequence consisted of a series of measurements with quantitative-, and manual pupillometry, performed subsequently to each other. Bland-Altman analysis with 95% limits of agreement (LoA) was used.

Results:
We included 14 sedated, comatose patients (6 females) with a mean age of 70 ± 12 years, resulting in 28 individual assessments. Quantitative pupillometry presented intraobserver variability with mean difference for maximum pupil size of 0.04 ± 0.13 with LoA of -0.21 to 0.28, and interobserver variability with mean difference of 0.03 ± 0.17 and of -0.31 to 0.36. For comparison, manual pupillometry revealed a mean difference of -0.02 ± 0.31 with LoA of -0.58 to 0.63, and -0.14 ± 0.44 with LoA of -1.00 to 0.71 for intra-, and interobserver variability, respectively. When comparing pupil size for left and right eyes, quantitative pupillometry resulted in LoA at -0.19, 0.25 (left) and -0.23, 0.32 (right), and LoA at -0.33, 0.39 (left) and -0.30, 0.34 (right) for intra-, and interobserver variability, respectively. Manual pupillometry presented LoA at -0.59, 0.63 (for both left and right), and LoA at -1.10, 0.79 (left) and -0.95, 0.83 (right) for intra-, and interobserver variability, respectively.

Conclusion:
Results from quantitative pupillometry are significantly more reproducible than manual measurements, suggesting it can be safely implemented in clinical practice for multimodal neuroprognostication of post-cardiac arrest patients.
Abstract 12011: Left Ventricular Hypertrophy Detected by Echocardiogram in Women With HIV
Authors: Inestroza Karla , Ebner Bertrand , Hurtado Vanessa , Satish Sanjana , Severdija Ryan , Loyd Quentin , Vincent Louis T , Grant Jelani , Martinez Claudia
Published: April 2022

Introduction:
Left ventricular hypertrophy (LVH) is an independent predictor of major cardiovascular events. People with HIV have an increased risk of cardiovascular disease (CVD), and a higher prevalence of LVH has been reported in this population. Women with HIV (WWH) have a higher CVD risk than their male counterparts. We sought to evaluate the current prevalence and characteristics of LVH in WWH.

Methods:
We performed a retrospective chart review (n=1,202) of patients seen at the University of Miami/Jackson Memorial Hospital Special Immunology clinic between 2017-2019. Of the 547 charts of WWH, 148 had available transthoracic echocardiogram. Data regarding demographic, clinical, imaging, and laboratory results was obtained.

Results:
The estimated prevalence of LVH in WWH was 25%. The mean age was 56.2 years. WWH with LVH were significantly older (60.7 vs. 54.9 years old, p=0.002), had higher systolic blood pressure (144 mmHg vs. 132 mmHg, p= 0.031), and left ventricle mass (169.2g vs. 128.7g, p<0.001). Those who had LVH had a higher prevalence of diastolic dysfunction (68.8% vs. 40.3%, p=0.007), diabetes (47.4% vs. 18.7%, p=0.001), hypertension (76.3% vs. 54.2%, p=0.017), heart failure (23.7% vs. 7.5% p=0.012), and CVD (47.4% vs. 24.3%, p=0.008). We found no significant difference in those with and without LVH regarding race, ethnicity, body mass index, ejection fraction, statin use, alcohol use, smoking, or HIV-related factors (CD4 count and an undetectable viral load).

Conclusions:
These findings suggest that WWH have a higher prevalence of LVH in the current era when compared to previous reports (15% in 2009). Furthermore, consistent with prior reports, WWH with LVH had a higher prevalence of CVD in this cohort. These findings emphasize the need to further assess risk and mechanisms for the development of LVH in WWH to help reduce CVD risk in this population.
Abstract 12013: Procollagen Type 1 N-terminal Propeptide, a Collagen Synthesis Biomarker, is Associated With Adverse Clinical Outcome in Patients With Suspected Acute Coronary Syndrome
Authors: Andersen Thomas , Nilsen Dennis W , Grundt Heidi , Staines Harry , Ueland Thor , Aukrust Pal , Kontny Frederic P
Published: April 2022

Introduction:
Procollagen type 1 N-terminal Propeptide (P1NP) is a precursor protein of collagen type 1, a major component of cardiac extracellular matrix. The association of P1NP to clinical outcome in patients with suspected acute coronary syndrome (ACS) has so far not been investigated. The objective of the present study was to assess the predictive value of P1NP concerning adverse clinical outcome in patients admitted for suspected ACS.

Methods:
Plasma P1NP was measured with an enzyme immune assay in samples taken upon admission from patients enrolled in the Risk markers in Acute Coronary Syndrome (RACS) study (NCT00521976), a Norwegian single center study including patients with suspected ACS from November 2002 to September 2003. The primary endpoint was a composite of all-cause mortality, myocardial infarction (MI), or stroke within 1 year. Additional analyzes included the composite and its individual components at 1, 2, and 7 years, and cardiac death at 1 and 2 years. Associations between quartiles of P1NP and the endpoints were assessed in both univariate analyzes and in stepwise multivariable Cox regression analyzes fitted with significant clinical variables, past medical history, medication, TnT, BNP, and eGFR before P1NP was introduced.

Results:
Samples were available from 813 patients (Mean age 69.6 years, 61.4 % males, 52.9% elevated TnT). Mean P1NP levels was 46.2 ng/mL (CI 44.8-47.6). In multivariable Cox analyzes, P1NP was found to be significantly associated with the composite of all-cause mortality, MI, or stroke at 1 year (HR [Q4vsQ1] 1.82, CI 1.12-2.98; p=0.017). This association did not remain significant beyond 1 year. No association was seen for any of the individual components, or cardiac death, at any timepoint, or in patients with elevated TNT (p>0.05 for all).

Conclusions:
This first study on P1NP in suspected ACS revealed a significant association with adverse clinical outcome (all-cause death, MI, or stroke) at 1 year. However, no predictive value was found concerning outcome for the individual components of the primary endpoint, or cardiac death, at any timepoint, or in patients with elevated TNT.
Abstract 12016: Surgical Mitral Valve Repair for Degenerative Mitral Regurgitation: Defining the Benchmark for Trans-Catheter Options
Authors: Del Forno Benedetto , D’Ovidio Mariangela , Carino Davide , Lapenna Elisabetta , Verzini Alessandro , Ascione Guido , Pinnarelli Luigi , Davoli Marina , Castiglioni Alessandro , Maisano Francesco , Alfieri Ottavio , De Bonis Michele
Published: April 2022

Introduction:
With the increasing trend of percutaneous treatment of mitral regurgitation (MR), defining the standard of care becomes crucial. The optimal treatment of degenerative MR has to provide excellent immediate and long-term outcomes. With this study we aim to present our results of surgical repair of degenerative MR.

Methods:
From January 2006 to December 2017, 4195 patients (median age 57 years [IQR 46;67], 68.9% men) underwent mitral valve repair (MVr) for degenerative MR at our Institution. The outcomes were retrieved using a deterministic record linkage with the National Health System, the National Tax Register and the clinical database. The follow-up was 100% complete. A Cox regression model was used to identify factors influencing outcomes. Kaplan-Meier estimates were used to assess survival. Competing risk analysis (CIF) with death as competing risk was used to assess the incidence of major adverse cardiovascular events and mitral valve (MV) reoperation.

Results:
The median EF was 60% [IQR 60;65], 17.8% of patients were in atrial fibrillation and 11.6% were in NYHA ≥3. Prolapse was posterior in 70.7%, bileaflet in 20.7%, and anterior in 8.5%. A resection technique was the most used approach (60.3%), followed by edge-to-edge (26.8%) and chordal implantation (9.2%). Thirty-day mortality was 0.5% (0.24% in isolated MVr cohort). At 13 years, overall survival was 86±13% (isolated MVr 90±10% vs non-isolated MVr 78±22% p <0.0001). At multivariate analysis male sex, age, cancer, previous admission for CHF, NYHA class ≥3, complex surgery, CPB time, MR >1+ at discharge and in-hospital stay were predictors of long-term mortality. At 13 years, CIF of rehospitalization for heart failure was 5.7±0.35% and CIF of MV reoperation was 1.9±0.2%. At multivariate analysis age, prolapse of the anterior leaflet and need of second pump run independently predicted reoperation.

Conclusions:
Surgical MVr can be performed with very low in-hospital mortality and excellent long-term survival in high-volume centers. At 13-years, in our series the rate of rehospitalization for heart failure was very low and MV reoperation was rare. These results can be used as surgical benchmark for percutaneous treatment of degenerative MR.
Abstract 12020: Heterogeneity and Plasticity of Cardiac Fibroblasts Governing Reparative Lymphangiogenesis After Myocardial Infarction: A New Therapeutic Approach for Heart Failure
Authors: Matsuoka Yuimi , Segard Bertrand D , Imamura Tomomi , Kimura Kodai , Ikeda Ayana , Matsuyama Makoto , Arai Mami , Machino Takeshi , Sato Akira , Murakoshi Nobuyuki , Iwamiya Takahiro
Published: April 2022

Introduction:
Cardiac lymphangiogenesis has attracted attention as a therapeutic target after myocardial infarction (MI). Lymphangiogenic remodeling has been observed after MI in adult and fetal hearts; however, reparative lymphangiogenic remodeling is only observed in fetal hearts. The factors that determine the fate of this phenomenon have not been fully elucidated.

Hypothesis:
We demonstrated that a specific population of VCAM1
+
human fetal cardiac fibroblasts (fCFs) restore cardiac function post-MI by lymphangiogenesis. Thus, we hypothesize that adult cardiac fibroblasts (aCFs), compared to fCFs, possess a different distribution of fibroblasts with differing lymphangiogenic potential. Furthermore, we also hypothesize that aCFs can be exogenously manipulated to acquire fCFs-like reparative lymphangiogenic potential, which can be used as a cell therapy for heart failure.

Methods:
Flow cytometry assessed CD90 and VCAM1 expression of aCFs and fCFs. To shift aCFs towards a fCF phenotype, TNF-α and IL-4 were added to culture medium. aCF subpopulations were intramyocardially injected in nude rats and swine post-MI with subsequent echocardiography. Myocardial tissue staining (Sirius Red, LYVE1) and RNA-seq were performed to identify the molecular mechanism.

Results:
aCFs and fCFs exhibited different distributions of CD90 and VCAM1 expression, where aCFs showed lower CD90 and VCAM1 expression. The addition of TNF-α and IL-4 shifted the localization of VCAM1
+
aCFs towards a fCF distribution by activation of NF-κB. VCAM1
+
CD90
+
fCFs-like aCFs provided a sustained improvement in left ventricular ejection fraction and showed reduced fibrosis and increased lymphangiogenesis. This effect was recapitulated in a large animal model. In terms of the molecular mechanism, 13 candidate genes were identified.

Conclusions:
These findings suggest that the heterogenous and plastic polarity of aCFs and fCFs determines the fate of the lymphangiogenic response after MI and that this response can be regulated by 13 genes. This artificial creation of the VCAM1
+
fCFs-like fibroblast environment after MI has enabled a clinical trial for a new cell therapy for inducing reparative lymphangiogenesis (clinical trial ID: jRCT2033210078).
Abstract 12025: Phosphodiesterase 3A Mutations Limit Hypertension-Induced Cardiac Damage
Authors: Ercu Maria ,   HTNB Consortium, Klussmann Enno
Published: April 2022

Hypertension affects more than 1 billion people worldwide and can cause cardiac hypertrophy and ultimately heart failure, a condition with an unmet medical need. We have shown that missense mutations in a 15 bp regulatory domain of the phosphodiesterase 3A (
PDE3A
) gene cause hypertension with brachydactyly type E (HTNB).
1, 2
We recently discovered two HTNB families with new mutations in the region encoding the catalytic domain of PDE3A. CRISPR-Cas9 was used to generate rat models of HTNB by introducing mutations in the regulatory or catalytic domain of the
PDE3A
gene. Surprisingly, despite the hypertension the hearts of the HTNB rats, even in response to catecholamine challenge, were similar to those of the wild type controls, as indicated by echocardiography. mRNA and protein expression analyses did hardly detect significant differences between the left ventricles of the mutant and wild type animals. However, the mutations consistently caused aberrations of PDE3A phosphorylation, enhanced interaction with the adaptor protein, 14-3-3θ, and aberrant cellular localisation. Fluorescence resonance energy transfer (FRET) experiments showed that all PDE3A mutants were hyperactive. Calcium imaging of cardiac myocytes isolated from the rat models revealed differences in calcium cycling between the mutants and wild type animals. Taken together, the data indicate that mutant PDE3A causes aberrant signalling, and suggest that an enhanced local activity of PDE3A is cardioprotective and may provide a basis for new approaches towards heart failure treatment.

1.Maass PG et al. PDE3A mutations cause autosomal dominant hypertension with brachydactyly.
Nat Genet
. 2015;47:647-53.2.Ercu M, Marko L et al. Phosphodiesterase 3A and Arterial Hypertension.
Circulation
. 2020;142:133-149.

HTNB Consortium: Ryan Walker-Gray, Anastasiia Sholokh, Claudia Loica, Tamara Pallien, Michael B. Mücke, Kerstin Zühlke, Andrea Geelhaar, Michael Russwurm, Lajos Markó, Theda U.P. Bartolomaeus, Hanna Napieczynska, Stefanie Schelenz, Martin Taube, Arnd Heuser, Tatiana Borodina, Daniele Yumi Sunaga-Franze, Jenny Eichhorst, Martin Lehmann, Fatimunnisa Qadri, Elena Popova, Reika Langanki, Sofia K. Forslund, Dominik N. Müller, Norbert Hübner, Sylvia Båhring, Michael Bader
Abstract 12033: Heart Rate and Estimated Glomerular Filtration Rate Decline in Kidney Transplant Recipients
Authors: Tantisattamo Ekamol , Mutirangura Pornthira , Polpichai Natchaya , Saowapa Sakditad , Eguchi Natsuki
Published: April 2022

Introduction:
Heart rate (HR) is one of the biomarkers reflecting sympathetic nervous system. It has been showed to be associated with decline in kidney function in general population. We aim to examine association between HR and change in estimated glomerular filtration rate (eGFR) in kidney transplant recipients (KTR).

Hypothesis:
We hypothesize that the higher HR is associated with more rapid decline in eGFR in KTR.

Methods:
A single center retrospective cohort study was conducted to examine association between mean HR among 4 office visits at 12-, 24-, 36-, and 48-weeks post-transplant and rate of eGFR change between 12- and 48-weeks post-transplantation by using multiple linear regression. In addition, association of the mean HR with rapid eGFR change defined as eGFR decline beyond a median eGFR change between 12- and 48-weeks post-transplantation of the unadjusted study population was tested by using multiple logistic regression.

Results:
Of all 105 KTR, mean age±SD was 54.33±11.60 years old and 61% was female. Median HR was 76/minute (IQR 69.5, 82.75). Mean eGFR were 57.23±1.74 and 60.58±1.89 ml/min/1.73 m
2
at 12 and 48 weeks, respectively with an increase in mean eGFR of -3.35±1.43 ml/min/1.73 m
2
(p 0.0211). Median rate of eGFR change was 4.31 ml/min/1.73 m
2
/year (IQR -5.75, 15.39). Every 1 beat/minute increase in HR was associated with a decline in eGFR of 0.3 ml/min/1.73 m
2
/year (β -0.297, p 0.093, 95%CI -0.644936, 0.0507214) and 1.01 time higher the odds of rapid change in eGFR (OR 1.007, p 0.662, 95%CI 0.9726614, 1.044582). After adjusted for age, gender, type of transplant, and induction immunosuppression, increase in 1 beat/minutes of HR was significantly associated with 0.39 ml/min/1.73 m
2
/year decline in eGFR (β -0.385, p 0.036, 95%CI -0.7456678, -0.0254736).

Conclusions:
Increased HR is associated with more rapid decline in eGFR in KTRs. Further studies are required elucidate underlying mechanisms by taken into account of immunological and non-immunological factors.
Abstract 12037: Neighborhood Environmental Correlates of Physical Activity Maintenance Among Healthy People in the Seoul Metropolitan City
Authors: Noh Songwhi , Choo Jina
Published: April 2022

Introduction:
Neighborhood environmental policy development to support physical activity (PA) maintenance are keys to the implementation of city-wide health promotion initiatives. These efforts may make citizens’ PA more maintainable and sustainable than any other efforts. However, there is lack of information on the identification of neighborhood environmental correlates of PA maintenance. We aimed to identify its neighborhood environmental correlates and to investigate whether the correlates would differ by PA mode, i.e., walking versus aerobic sports.

Methods:
Participants were 1,449 healthy citizens of the Seoul Metropolitan city. Neighborhood environment variable was perceived by respondents, as measured by the Physical Activity Neighborhood Environmental Scale (PANES). PANES can be evaluated by full- and sub-scale scores. Walking maintenance was defined as daily
>
30 minutes on 5 days or more in a behavioral maintenance stage of 6 months or greater. Aerobic sports included leisure-time physical sports (e.g., hiking, bicycling, or other sports) and its maintenance was defined as either
>
150 minutes of moderate-intensity exercises or
>
75 minutes of vigorous-intensity exercises in a behavioral maintenance stage of 6 months or greater.

Results:
Both walking maintenance (odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.09 - 1.21) and the maintenance of aerobic sports (OR = 1.05, 95% CI = 1.01 - 1.10) were significantly associated with the PANES full score. Specifically, walking maintenance was significantly associated with the sub-scale scores of land use mix (OR = 1.42), recreation facilities (OR = 1.56), and aesthetics (OR = 1.42). The maintenance of aerobic sports was significantly associated with bicycling infrastructures (OR = 1.22), recreation facilities (OR = 1.50) and traffic safety (OR = 0.78).

Conclusions:
Neighborhood environmental correlates of PA maintenance differed by walking vs. aerobic sports. Overall, city-wide neighborhood environmental policy makers should consider these differences, and prioritize the increases and improvements in availability and accessibility of public recreation exercise facilities (that is a common correlate) for PA maintenance in Seoul Metropolitan city.
Abstract 12050: Dapagliflozin Therapy is Associated With Improved Left and Right Ventricular Function in Chronic Heart Failure Patients With Reduced Ejection Fraction
Authors: Poglajen Gregor , orž Neža , Frljak Sabina , Cerar Andraž , Okrajek Renata , ebetjen Miran , Zemljic Gregor , Vrtovec Bojan
Published: April 2022

Introduction:
Although sodium-glucose transporter 2 inhibitors (SGLT2i) were shown to improve clinical outcomes of patients with heart failure with reduced ejection fraction (HFrEF), data on the effects of SGLT2i on myocardial function are scarce.

Hypothesis:
We evaluated the effects of dapagliflozin on left and right ventricular function in HFrEF patients.

Methods:
In a prospective sequential pilot clinical study we enrolled 14 HFrEF patients with NYHA II or III heart failure symptoms and LVEF<40%. In Phase I, all patients were treated with optimized heart failure therapy including sacubitril/valsartan, beta blockers and spironolacton. After 3 months, dapagliflozin (10 mg qd) was added to the regimen and the patients were followed for another 3 months (Phase II). At baseline, 3- and 6- month follow-up we collected clinical, biochemical and echocardiographic data. Renal dysfuntion was defined as eGFR<90 ml/min/1,73m
2
.

Results:
Of 14 patients, 10 (71%) were male; the average age was 57±16 years. Ishemic and non-ischemic heart failure was present in 3 (21%) and 11 (79%) of patients, respectively; 7 (50%) had renal dysfunction, 3 (21%) had diabetes and 6 (43%) had a history of hypertension. In Phase I we found no significant changes in LVEF (from 28±9% to 28±8%, P=0.91), left ventricular outflow tract VTI (LVOT VTI: from 12.8±3.6 cm to 13.3±5.3, P=0.80), or TAPSE (1.8±0.3 cm vs. 1.7±0.4 cm, P=0.62). Also, there were no significant changes in NYHA functional class (from 2.5±0.5 to 2.4±0.6, P=0.66), and NT-proBNP levels (from 1557±1745 pg/mL to 1677±1467 pg/mL, P=0.86). In contrast, in Phase II, we found a significant increase in LVEF (from 28±8% to 35±9%, P=0.02) and TAPSE (from 1.7±0.4 cm to 2.1±0.3 cm, P=0.04), and a trend of increase in LVOT VTI (from 13.3±5.3 cm to 16.7±3.4, P=0.07). In addition, after dapagliflozin therapy, we found a significant decrease in NYHA functional class (from 2.4±0.6 to 1.7±0.5, P=0.01) and NT-proBNP levels (from 1677±1467 pg/mL to 773±523, P=0.03).

Conclusions:
Dapagliflozin appears to improve echocardiographic parameters of left and right ventricular function in patients with HFrEF. Changes in heart function after dapagliflozin therapy occur in parallel with impovements in heart failure symptoms and levels of NTproBNP.
Abstract 12055: Immediate Effect of Yoga Based Om-Meditation on Heart Rate Variability During Different Phases of Menstruation
Authors: Kanuga Mansha , Patil Satish G
Published: April 2022

Introduction:
Stress may play a role in causing menstrual irregularities predisposing to increased risk for cardiovascular disease (CVD). Stress and cyclic variations in endogenous hormone levels during the menstrual cycle (MC) may affect heart rate variability (HRV), a measure of cardiac autonomic function (CAF) and mental stress. Strategies that reduce stress and improve HRV may prevent menstrual irregularities and thus CVD. We evaluated the effect of yoga-based OM-meditation on HRV during different phases of MC in young healthy females.

Methods:
A non-randomized controlled study was conducted on healthy young females (n=20) with normal menstrual cycle. Meditation group subjects (n=10) practiced Om-meditation while control group subjects (n=10) relaxed quietly for 10 minutes. Each subject received an intervention thrice during menstrual, proliferative and secretory phase. Data was collected before and immediately after every intervention. BMI, blood pressure (BP), heart rate (HR) and HRV were measured. Frequency domain method was used for an analysis of HRV.

Results:
The mean age of participants was 19.2±0.79 and 19.3±0.82 years; and mean period of MC was 31.1±2.76 and 30.3±2.4 days in meditation and control group respectively. There was no change in the baseline values of BMI, BP and HR between two groups and were within normal range. Between group analysis (ANCOVA) of HRV spectrum showed that Om-meditation had significantly decreased low frequency (LF) component of HRV (p<0.05) and LF/HF ratio (p<0.05); and increased high frequency (HF) component (p<0.05) of HRV during all the three phases of MC.

Conclusion:
These results suggest that practice of Om-meditation for 10 minutes can induce beneficial changes in HRV by reducing sympathetic activity and shifting autonomic balance towards parasympathetic dominance. Om-meditation may reduce mental stress and optimize CAF during different phases of MC. However, this needs an evaluation in a larger trial.
Abstract 12056: Incidence of Actionable Events on Implantable Cardiac Monitors: A Prospective Study Comparing Reveal LINQ
TM
and Confirm Rx
TM
Implantable Cardiac Monitors
Authors: Banga Sandeep , Baloch Zulfiqar Q , Prasad Rohan M , Ali Abbas , Al-abcha Abdullah , Ip Randy , Sheth Reema , Ip John
Published: April 2022

Introduction:
Implantable cardiac monitors (ICM) are increasingly being used to detect and treat arrhythmias in various clinical settings such as cryptogenic stroke. However, the incidence of actionable events in ICMs is unknown.

Hypothesis:
Confirm Rx
TM
has more actionable event detection rate than Reveal LINQ
TM

Methods:
We prospectively studied 411 patients who received Reveal LINQ
TM
(Medtronic Inc., Dublin, Ireland) or Confirm Rx
TM
(Abbott, Sylmar, CA) ICM system for diagnosis of actionable arrhythmic events. Actionable arrhythmic events were defined as atrial fibrillation (AF) requiring anticoagulation, pauses requiring pacemaker, and tachycardia requiring ablation or medication changes. All actionable events were adjudicated for accuracy.

Results:
This study evaluated 411 patients with baseline characteristics of: 52.1% females, an average age of 65.81 years, and an average body mass index of 29.9 kg/m
2
. Reasons for ICM implants were, in descending order: cryptogenic stroke (44.3%), syncope (35%), and palpitations (20.9%). The Reveal LINQ
TM
was used in 56.4% (n=232) of patients and Confirm Rx
TM
was used in the other 43.6% (n=179). On univariate analysis, the composite outcome of actionable events were similar in both groups (Reveal LINQ
TM
19% vs Confirm Rx
TM
19%, p>0.9). The individual actionable event outcome were also similar in both groups: AF (Reveal LINQ
TM
11% vs Confirm Rx
TM
8.5%, p=0.6), pauses (Reveal LINQ
TM
1.3% vs Confirm Rx
TM
4.0%, p=0.2), tachycardia (Reveal LINQ
TM
6.0% vs Confirm Rx
TM
5.6%, p>0.9). However, the time to actionable event or last follow-up was significantly reduced (p<0.001) in the Confirm Rx
TM
(median 203 days, interquartile range 90-371 days) as compared to Reveal LINQ
TM
(median 300 days, interquartile range 128-488 days).

Conclusions:
This study showed that although Reveal LINQ
TM
and Confirm Rx
TM
have similar actionable event detection rates, Confirm Rx
TM
has a shorter duration to diagnose true arrhythmic events. This difference may be due to their intrinsic detection algorithm. Larger studies are required to confirm this finding.
Abstract 12057: GDF15 and CHI3L1 Are Associated With a High-Risk Phenotype in Heart Failure Patients - Results From the Harvest-Malmö and Media-DHF Cohorts
Authors: Dieden Anna , Girerd Nicolas , Molvin John , Korduner Johan , Gudmundsson Petri , Bachus Erasmus , Holmes Hannes , Duarte Kevin , ZANNAD Faiez , Jujic Amra , Magnusson Martin
Published: April 2022

Introduction:
Even though treatment for heart failure (HF) has improved over recent decades, the mortality is still high, and the high re-hospitalization rate poses a huge economic burden to the society.

Hypothesis:
Here, we explored if proteomic profiles differed between high mortality risk/multiple hospitalized HF patients versus HF patients that survived without multiple hospitalizations.

Methods:
A multiplex protein panel was analysed in patients hospitalized for HF (The Swedish heart failure cohort (HARVEST-Malmö) discovery cohort: n=296; mean age 74.6 years; 30% women) and a replication cohort, the European MEDIA-DHF cohort (n=430). We characterized three mutually exclusive phenotypes of HF based on vital and hospitalization status (survivors without multiple hospitalizations (≥2; n=50); deceased without multiple hospitalizations (n=46) and multiply hospitalized but not dead (n=86), and explored associations between proteins and phenotype in multivariate logistic regressions.

Results:
In the discovery cohort, SCGB3A2 (OR 2.51 (1.14-5.52; p=0.023); elafin (OR 2.50 (1.01-6.14; p=0.047), GDF15 (OR 2.82 (1.07-7.42); p=0.036) and CHI3L1 (3.09 (1.42-6.72); p=0.004) presented with significant associations with death without multiple hospitalizations. GDF15 and CHI3L1 also presented with associations with multiple hospitalizations. SCGB3A2, elafin, In the replication cohort GDF15 and CHI3L1 were both associated with death without multiple hospitalizations (n=9) a model adjusted for age and sex. When associations between GDF15 and CHI3L1 and multiple hospitalizations were explored in the replication cohort, GDF15but not CHI3L1 presented with significant associations in a model adjusted for age and sex (p=0.005 and p=0.900, respectively), but the association was attenuated upon further adjustment (p=0.80).

Conclusions:
In two European hospitalized HF populations, we could show associations between GDF15 and CHI3L1 and a high-risk phenotype of HF in both the discovery and replication cohorts.
Abstract 12071: Emergent Temporary Transvenous Pacemakers Were Infrequently Needed for Patients Presenting With Complete Heart Block at a Regional Hospital
Authors: MAHALWAR GAURANGA , Lao Nicole , Bashir Hanad , Iyer Indiresha
Published: April 2022

Introduction:
Patients presenting with Complete heart block (CHB) are emergently referred for placement of a temporary transvenous pacemaker (TTVP) for hemodynamic stability. Data on the immediate management and outcomes of such patients are lacking.

Methods:
Data collected; through retrospective chart review of patients presenting to the Emergency Department (ED) at a regional hospital from October 2017 to January 2021 with a diagnosis of new CHB; included age, sex, clinical, laboratory and ECG data, medications, interventions and length of stay.

Results:
There were 71 patients (31 women) of whom 19 were on beta blocker or Calcium channel blockers. Data (see Table 1) for all variables was available in 68 patients. Syncope, lightheadedness and dyspnea were common symptoms. The median age was 77 years. The median heart rate was 41bpm. Atropine was used in 13 patients. Five patients with initial Systolic Blood Pressure (SBP) < 100mmHg received sympathomimetics. Syncope with pause occurred in 3 patients. A TTVP was placed in 12 patients. Among 22 patients with initial SBP > 160mmHg one patient with a recent TAVR had a TTVP placed. All but five were managed in the ICU setting. On Univariate logistic regression (R statistical software 3.6.1) initial SBP, SBP < 100mmHg and Initial Serum K level were clinically significant. In multivariate analysis, SBP was significant with a lower SBP predicting need for a TTVP [OR 0.96 (CI 0.91 - 0.99, p = 0.019)]. A permanent pacemaker (PPM) prior to discharge was placed in 64 patients on average in 1.6 days from presentation. 3 patients with STEMI and TTVP did not need a PPM. 1 transitioned to hospice and 1 patient died of sepsis. In 1 it was attributed to COVID-19 infection.

Conclusions:
TTVP was infrequently needed (16.66%) among patients presenting to the ED with CHB. Initial SBP and Serum K were clinically relevant factors. Prospective data related to the acute management of CHB is needed to identify predictors that can improve the care for such patients.
Abstract 12077: Reduced Potency of Blood Pressure Lowering Drugs in the Presence of Diabetes Mellitus - Results from the Triumph Randomized Controlled Trial
Authors: Gnanenthiran Sonali , Webster Ruth , Salam Abdul , de Silva Asita , Schutte Alta , Patel Anushka , Rodgers Anthony
Published: April 2022

Introduction:
Whether the presence of diabetes mellitus (DM) affects the ability of antihypertensive therapies to lower blood pressure (BP) is uncertain. We investigated whether DM affects the efficacy of a low dose triple combination pill or usual care among people with hypertension.

Methods:
TRIUMPH (TRIple pill vs Usual care Management for Patients with mild-to-moderate Hypertension) was a randomized controlled open-label trial of patients requiring initiation or escalation of antihypertensive therapy. Patients from urban hospital clinics in Sri Lanka were randomised to a once-daily low-dose triple combination polypill (telmisartan 20mg, amlodipine 2.5mg, chlorthalidone 12.5mg) or standard care. This analysis compared BP reduction and percentage of time below 140/90mmHg (time at target) in the intervention and usual care groups over 24 week follow-up, stratified by the presence of DM. Predicted potency of therapy was calculated according to estimation methods of Law et al.

Results:
The trial comprised 700 patients (56±11yrs, 58% women, 31% DM). Patients on the triple pill achieved greater BP reduction compared to standard care at week 24 in both diabetic and non-diabetic groups (Table 1, p>0.05 for heterogeneity). DM was a negative predictor of time at target BP (OR 0.18, 95%CI 0.10-0.31, p<0.001). Observed BP reduction from baseline to week 24 was lower in diabetics compared to non-diabetics on the triple pill (25/11 vs 31/15 mmHg, p≤0.01) and on usual care (17/7 vs 22/11, p≤0.01). Diabetics also achieved lower time at target BP than non-diabetics in the triple pill group (44% vs 73%, p<0.001) and in usual care (27% vs 51%, p<0.001). This was despite no difference between diabetics and non-diabetics in number of drugs prescribed or predicted potency of therapy.

Conclusion:
While both drug regimens were associated with reduced potency in the presence of DM, the triple pill achieved greater BP reduction compared to usual care in mild-moderate hypertension.
Abstract 12082: Disparities in Medical Care and Impact on Secondary Cardiovascular Complications Among Patients With Peripheral Artery Disease: A Report From the PAD Go Pro Quality Program
Authors: Bunte Matthew C , Gosch Kensey , Vupputuri Sravanthi
Published: April 2022

Introduction:
Guideline-directed optimal medical treatment (OMT) is known to reduce secondary cardiovascular risk among those with peripheral artery disease (PAD). Rates of OMT have been reported lowest among minority subgroups.

Hypothesis:
Race and ethnic identity are associated with differences in rates of OMT and secondary cardiovascular (CV) complications among a large, metropolitan population with PAD.

Methods:
From a single-system quality improvement registry, we evaluated rates of OMT and major adverse CV events (MACE), including all-cause death, myocardial infarction, and stroke. OMT was defined as use of an antiplatelet agent, statin, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker if hypertensive, and tobacco abstention if smoking. Patients were stratified based on baseline OMT status, then censored for MACE events.

Results:
From January 1, 2016-May 31, 2021, 15,107 outpatients with PAD had a mean age of 72.5 +/- 10.9 years, 46.5 % were female, and 89.6% identified as non-Hispanic White (NHW), 8.4% as non-Hispanic Black (NHB), and 2.0% as Hispanic/Latino (H/L). OMT was provided to 28.2% of patients overall. Rates of OMT provided to NHW, AA, and H/L cohorts were 28.2%, 26.9%, 32.6%, respectively (p=0.14). Among all patients with OMT at baseline (n=4263), 5-year rates of MACE were higher among NHB compared to NHW and H/L groups (31.9% vs 23.8% vs 24.6%, p=0.004). Among NHB, those receiving OMT had a lower risk of MACE at 5 years (31.9% vs 41.2%; log-rank p=0.014). OMT was similarly associated with reductions in MACE at 5 years within the H/L cohort (24.6% vs 47.7%; log-rank p=0.032).

Conclusions:
Rates of OMT to reduce secondary CV risk among those with ambulatory PAD are poor overall, and lowest among NHB subgroups. Non-OMT was associated with worse outcomes among all subgroups. Additional analysis to evaluate baseline differences, particularly regarding those affecting the provision of OMT, are warranted.
Abstract 12086: Relationship of Cardiac Rhythm and Other Electrocardiogram Findings with Sites of Wall Thickening and Abnormal Late Enhancement in Patients with Confirmed Cardiac Amyloidosis
Authors: Funabashi Nobusada , Nakamura Kohki , sasaki takehio , Naito Shigeto , Kobayashi Yoshio
Published: April 2022

Introduction:
Left ventricular (LV) wall thickening and diastolic dysfunction on TTE without high voltage R wave on ECG to a diagnosis of cardiac amyloidosis (CA). However, amyloid sometimes invade right ventricle (RV), and left (LA) and right (RA) atria to cause ECG changes such as sick sinus syndrome (SSS), arrhythmia, and QRS axis deviation.

Hypothesis:
We hypothesized that sites of wall thickening and abnormal late enhancement (LE) on cardiac CT and MRI, suggesting amyloid invasion, correlated with cardiac rhythm and other ECG findings in patients with CA confirmed by biopsy.

Methods:
26 patients (11 females) with suspected CA, showing LV wall thickening by TTE without a high voltage R wave, underwent cardiac CT. 5 patients (3 females, mean 73 years) were diagnosed with CA: complicated multiple myeloma, 2; senile ATTR (transthyretin) amyloidosis, 1; immunoglobulin light chain amyloidosis 1; and transthyretin mutation, 1. 4 patients underwent cardiac MRI.

Results:
2 patients (cases 1 and 2) had SSS (junctional rhythm), 1 had atrial tachycardia, and the remaining 2 (cases 4 and 5) had a normal sinus rhythm. In case 1, ECG showed a left QRS axis deviation, no low voltage R wave and a mild LA load. Wall thickening in basal interventricular septum (IVS), LV inferior-posterior wall, LA on CT, LE in endocardium in whole LV, RV, and RA on CT, and LE in endocardium in whole LV, RV, LA, and IVS on MRI were observed. In case 2, ECG showed a normal QRS axis, no low voltage R wave, no LA load, wall thickening in whole LV, RV, LA, and IVS on CT, and unclear (CT) or no (MRI) LE. In case 3, ECG showed a normal QRS axis, with low voltage R wave, no LA load, wall thickening in LA and basal IVS on CT, LE in LA and basal IVS on CT, and LE in LA only on MRI. In case 4, ECG showed left QRS axis deviation, a low voltage R wave, and no LA load, wall thickening in LA and RV on CT, unclear LE on CT, and LE in whole LV, endocardium in RV, and whole IVS on MRI. In case 5, ECG showed a right QRS axis deviation, low voltage R wave, and a mild LA load, wall thickening in IVS, LV lateral wall, LV anterior wall, RA, RV outflow tract, and RA appendage, and no LE on CT (MRI not performed).

Conclusions:
The presence of wall thickening and abnormal LE in RV, LA, and RA in addition to LV on CT or MRI would be important which may influence ECG changes in patients with CA.