bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value of CHA2DS2-VASc score and safe contrast volume for early detection of contrast induced nephropathy after percutaneous coronary intervention
Authors: Khalil W , Gouda M , Gamal M , Alshaer M 
Published: October 2021

Abstract

Background
The CHA2DS2-VASc score is utilized to order the danger of embolization in atrial fibrillation (AF). Also it has been assessed to expect the worse clinical scenario in acute coronary syndrome patients, regardless of having AF. Therefore, the study aim was to use CHA2DS2-VASc score that has such a large area of use and the safe contrast volume – that represented by volume of the dye to creatinine clearance ratio (V/CrCl) – for contrast induced nephropathy (CIN) early detection after PCI.

Patients and methods
A total of 259 patients who underwent elective or primary PCI were enrolled in the study. For each patient, The CHA2DS2-VASc score and V/CrCl was evaluated. The patients in our study were divided, according to CIN development to two groups. CIN was identified as a rise in serum creatinine &gt;0.5 mg/dl or &gt;25% increase in baseline within48 to 72 hours after PCI. Statistical analysis: the receiver operating characteristic analysis was used to detect the best cut off values to predict CIN, and we concluded the independent predictors of CIN through multivariate logistic regression analysis.

Results
There was significant positive correlation between Mehran score and CHA2DS2-VASc score. Independent predictors of CIN were Mehran score, V/CrCl ratio&gt;3.2 and CHA2DS2-VASc &gt;3, CHF or EF &lt;40%, hypotension, anemia, primary PCI and weight. If the patient had (CHA2DS2-VASc score&gt;3 or V/CrCl &gt;3.2), as a single predictor, we can predict CIN with (sensitivity 96.97%, 95% CI 0.71 to 0.82).

Conclusion
The Mehran score, V/CrCl ratio and CHA2DS2-VASc score are strong predictors of CIN, and we can use CHA2DS2-VASc score and safe contrast volume for early detection of CIN after PCI.

Funding Acknowledgement
Type of funding sources: None.
Sex-related differences in long-term mortality after coronary artery bypass graft surgery: a systematic review and meta-analysis
Authors: Al-Sadawi M , Kane J , Stevens G A , Parikh P 
Published: October 2021

Abstract

Background
This meta-analysis assessed the sex-related differences in long-term mortality (&gt;7 years) after Coronary Artery Bypass Graft (CABG) Surgery.

Purpose
Women has higher incidence of short-term cardiovascular mortality after CABG compared to men. However, data about long-term differences are controversial.

Methods
We searched the databases for studies reporting sex-specific mortality following CABG including Ovid MEDLINE, Ovid, Embase, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 31st, 2020. The search was not restricted to time or publication status. Outcomes included rates of long-term mortality (&gt;7 year or longer).

Results
A total of 518 studies were resulted from literature search. A total of 14 studies and 204,223 patients; 158,663 men and 45,556 women, with a mean age of the men 60.2 years and 63.2 years for women, were included in our systematic review and meta-analysis. Our analysis suggested sex-related differences in long-term mortality (&gt;7 years) following CABG (odds ratio (1), 1.15; 95% confidence interval (2), 1.017–1.30; P&lt;.02).

Conclusions
Our results suggest that women had higher long-term mortality following CABG compared with men. It is the largest study to date of sex-specific differences in long-term mortality (&gt;7 years).

Funding Acknowledgement
Type of funding sources: None. Meta-analysisDemographics
Reintervention for the trifecta aortic bioprosthesis: large single-centre series
Authors: Fard A , Al-Attar N 
Published: October 2021

Abstract

Introduction
Aortic valve replacement with the Trifecta aortic bioprosthesis has reported favourable haemodynamic performance. However, several reports of structural valve deterioration have raised concerns of design risks and its long-term durability.

Purpose
We conducted this study to assess reintervention and outcomes in a large single-centre cohort of 944 patients receiving the Trifecta valve over a 10-year period.

Methods
Consecutive patients undergoing aortic valve replacement with the Trifecta valve between October 2011 and October 2020 in our centre were included in this study. Perioperative patient and operative characteristics were prospectively recorded in an independent database. Reintervention was recorded as a surrogate for structural valve deterioration, and survival data was analysed.

Results
A total of 944 patient (mean age 72.82 years ± 8.13, range 28–91, 58% male) underwent aortic valve replacement with the Trifecta valve in our centre between October 2011 and October 2020. At 10-years, 1.4% of patients required a redo operation for aortic valve replacement, giving an overall freedom reintervention of 98.6%, with a 99.3% and 99.4% freedom from reintervention due to structural valve deterioration and infection, respectively. The mean time to all-cause reintervention was 48.87 months, and the mean time to reintervention due to SVD was 68.87 months. Patients that did not require reintervention had a 97.74% freedom from mortality and those that underwent reintervention had a freedom from mortality of 84.62% with a median survival of 69-days.

Conclusions
In a large single-centre cohort, the Trifecta aortic bioprosthesis was safe with a 1.4% all-cause reintervention rate and a 0.7% reintervention rate for structural valve deterioration at 10-years.

Funding Acknowledgement
Type of funding sources: None.
Comparison of deep learning with traditional models to predict preventable acute care use and spending among heart failure patients
Authors: Lewis M , Figueroa J 
Published: October 2021

Abstract

Recent health reforms have created incentives for cardiologists and accountable care organizations to participate in value-based care models for heart failure (HF). Accurate risk stratification of HF patients is critical to efficiently deploy interventions aimed at reducing preventable utilization. The goal of this paper was to compare deep learning approaches with traditional logistic regression (LR) to predict preventable utilization among HF patients. We conducted a prognostic study using data on 93,260 HF patients continuously enrolled for 2-years in a large U.S. commercial insurer to develop and validate prediction models for three outcomes of interest: preventable hospitalizations, preventable emergency department (ED) visits, and preventable costs. Patients were split into training, validation, and testing samples. Outcomes were modeled using traditional and enhanced LR and compared to gradient boosting model and deep learning models using sequential and non-sequential inputs. Evaluation metrics included precision (positive predictive value) at k, cost capture, and Area Under the Receiver operating characteristic (AUROC). Deep learning models consistently outperformed LR for all three outcomes with respect to the chosen evaluation metrics. Precision at 1% for preventable hospitalizations was 43% for deep learning compared to 30% for enhanced LR. Precision at 1% for preventable ED visits was 39% for deep learning compared to 33% for enhanced LR. For preventable cost, cost capture at 1% was 30% for sequential deep learning, compared to 18% for enhanced LR. The highest AUROCs for deep learning were 0.778, 0.681 and 0.727, respectively. These results offer a promising approach to identify patients for targeted interventions.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): internally funded by Diagnostic Robotics Inc.
Prostaglandin E1 attenuates AngII-induced cardiac hypertrophy via EP3 receptor activation and Netrin-1upregulation
Authors: Shen L , Shen Y , Wang X , He B 
Published: October 2021

Abstract

Aims
Pathological cardiac hypertrophy induced by activation of the renin–angiotensin–aldosterone system (RAAS) is one of the leading causes of heart failure. However, in current clinical practice, the strategy for targeting the RAAS is not sufficient to reverse hypertrophy. Here, we investigated the effect of prostaglandin E1 (PGE1) on angiotensin II (AngII)-induced cardiac hypertrophy and potential molecular mechanisms underlying the effect.

Methods and results
Adult male C57 mice were continuously infused with AngII or saline and treated daily with PGE1 or vehicle for two weeks. Neonatal rat cardiomyocytes were cultured to detect AngII-induced hypertrophic responses. We found that PGE1 ameliorated AngII-induced cardiac hypertrophy both in vivo and in vitro. The RNA sequencing (RNA-seq) and expression pattern analysis results suggest that Netrin-1 (Ntn1) is the specific target gene of PGE1. The protective effect of PGE1 was eliminated after knockdown of Ntn1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the PGE1-mediated signaling pathway changes are associated with the mitogen-activated protein kinase (MAPK) pathway. PGE1 suppressed AngII-induced activation of the MAPK signaling pathway, and such an effect was attenuated by Ntn1 knockdown. Blockade of MAPK signaling rescued the phenotype of cardiomyocytes caused by Ntn1 knockdown, indicating that MAPK signaling may act as the downstream effector of Ntn1. Furthermore, inhibition of the E prostanoid (EP)3 receptor, as opposed to the EP1, EP2, or EP4 receptor, in cardiomyocytes reversed the effect of PGE1, and activation of EP3 by sulprostone, a specific agonist, mimicked the effect of PGE1.

Conclusion
In conclusion, PGE1 ameliorates AngII-induced cardiac hypertrophy through activation of the EP3 receptor and upregulation of Ntn1, which inhibits the downstream MAPK signaling pathway. Thus, targeting EP3, as well as the Ntn1–MAPK axis, may represent a novel approach for treating pathological cardiac hypertrophy.

Funding Acknowledgement
Type of funding sources: None.
Sterile inflammation through Ca2+/ Calmodulin-dependent protein kinase II signaling is essential for adverse cardiac remodeling
Authors: Suetomi T , Okuda S , Okamoto Y , Tateda S , Uchinoumi H , Oda T , Kobayashi S , Yamamoto T , Yano M 
Published: October 2021

Abstract

Introduction and hypothesis
Sterile inflammation is associated with cardiac remodeling in response to non-ischemic stress, but how it is initiated in the absence of cell death and how it is propagated are not well elucidated. We tested the hypothesis that activation of CaMKII in cardiomyocytes and macrophages in response to pressure overload initiates inflammatory responses leading to adverse cardiac remodeling.

Methods and results
Cardiomyocyte specific CaMKIIδ knockout (CKO) mice were subjected to transverse aortic constriction (TAC). CaMKII and NFkB activation were significantly increased in control fl/fl (CTL) but not in CKO hearts. Cardiac mRNA levels for pro-inflammatory cytokines also increased vs sham. These responses were significantly attenuated in the CKO mice. Activated NLRP3 inflammasome was shown by elevated caspase-1 activity in isolated cardiomyocytes of CTL while attenuated in CKO. Macrophage accumulation was attenuated in the CKO and NLRP3 inhibitor MCC950 treated mice. Cardiac fibrosis and subsequent cardiac dysfunction were less impaired in the CKO vs CTL (ejection fraction 43±3% vs 33±5%). Upregulated NLRP3 gene expression, elevated CaMKII and caspase-1 activity were observed in neonatal mouse cardiomyocytes (NMCMs) in response to osmotic stretch. Increased caspase-1 activity was observed in macrophages cultured with media from osmotic-stretched NMCMs and it was attenuated by pretreatment of CaMKII inhibitor KN-93. Coincubation with stretched NMCMs induced inflammatory responses in isolated macrophages from wild-type mice but not in isolated macrophages from KN-93 pretreated mice.

Conclusions
Activated CaMKIIδ in response to pressure overload triggers inflammatory signals including NLRP3 inflammasome cascade in cardiomyocytes. CaMKII could also contribute amplification of inflammasome signal in macrophages leading fibrosis and consequent cardiac dysfunction. CaMKII in cardiomyocytes and macrophages could be a therapeutic target to prevent progression of non-ischemic heart failure.

Funding Acknowledgement
Type of funding sources: None.
A variant noncoding region regulates Prrx1 and predisposes to atrial arrhythmias
Authors: Bosada F M , Rivaud M R , Uhm J.-S , Verheule S , Van Duijvenboden K , Verkerk A O , Christoffels V M , Boukens B J 
Published: October 2021

Abstract

Rationale
Atrial Fibrillation (AF) is the most common cardiac arrhythmia diagnosed in clinical practice. Genome-wide association studies have identified AF-associated common variants across 100+ genomic loci, but the mechanism underlying the impact of these variant loci on AF susceptibility in vivo has remained largely undefined. One such variant region, highly associated with AF, is found at 1q24, close to PRRX1, encoding the Paired Related Homeobox 1 transcription factor.

Objective
To identify the mechanistic link between the variant region at 1q24 and AF predisposition.

Methods and results
The mouse orthologue of the noncoding variant genomic region (R1A) at 1q24 was deleted using CRISPR genome editing. Among the genes sharing the topologically associated domain with the deleted R1A region (Kifap3, Prrx1, Fmo2, Prrc2c), only the broadly expressed gene Prrx1 was downregulated in mutants, and only in cardiomyocytes. Expression and epigenetic profiling revealed that a cardiomyocyte lineage-specific gene program (Mhrt, Myh6, Rbm20, Tnnt2, Ttn, Ckm) was upregulated in R1A−/− atrial cardiomyocytes, and that Mef2 binding motifs were significantly enriched at differentially accessible chromatin sites. Consistently, Prrx1 suppressed Mef2-activated enhancer activity in HL-1 cells. Mice heterozygous or homozygous for the R1A deletion were susceptible to atrial arrhythmia induction, had atrial conduction slowing and more irregular RR intervals. Isolated R1A−/− mouse left atrial cardiomyocytes showed lower action potential upstroke velocities and sodium current, as well as increased systolic and diastolic calcium concentrations compared to controls.

Conclusion
The noncoding AF variant region at 1q24 modulates Prrx1 expression in cardiomyocytes. Cardiomyocyte-specific reduction of Prrx1 expression upon deletion of the noncoding region leads to a profound induction of a cardiac lineage-specific gene program and to propensity for AF. These data indicate that AF-associated variants in humans may exert AF predisposition through reduced PRRX1 expression in cardiomyocytes.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Fondation Leducq
Clinical and morphological characteristics of COVID-19-associated myocarditis
Authors: Kogan E A , Kukleva A D , Blagova O V , Berezovskij Y U S 
Published: October 2021

Abstract

Background
COVID-19 is accompanied by the development of a wide range of cardiovascular lesions. The goal: to study the clinical and morphological features of SARS-CoV-2-associated myocarditis (SCM), determining the presence of viral RNA and proteins in myocardial tissue.

Methods
The study was based on 32 autopsies with a confirmed diagnosis of myocarditis. The average age of the patients was 72.7±15.5 years. Men predominated in the group (53%). The immunohistochemical determination of the surface markers of CD45, CD3, CD20, CD 68 inflammatory infiltrates and SARS-CoV-2 nucleocapsid and spike protein has been done. Detection of coronavirus RNA was performed.

Results
The clinical manifestations SCM included heart failure and variety of rhythm disturbances. Increased level of anticardiac antibodies was detected. Lymphomacrophage infiltrates (more than 7 CD3+ T-lymphocytes, more than 14 CD45+ lymphocytes and more than 7 CD68+ macrophages per 1 mm2) were found in 100% of cases. RNA of the virus was detected in myocardial tissue. Virus proteins were identified in macrophages of the inflammatory infiltrate and cardiomyocytes.

Conclusion
The results suggest persistence of the virus in the myocardium and the development of chronic myocarditis.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Russian Foundation for Fundamental Research
Improvement of retinal microvascular function after initiation of lipid-lowering therapy with PCSK9 inhibitors – an observational study
Authors: Naegele M , Raemy Y , Barthelmes J , Kreysing L , Haider T , Ruschitzka F , Flammer A J , Sudano I 
Published: October 2021

Abstract

Background
Hypercholesterolemia is associated with endothelial dysfunction. While good evidence exists for the beneficial endothelial effects of first-line lipid-lowering drugs (statins), less is known on the new class of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. This is particularly true for the differential effects on micro- and macrovascular endothelial function and arterial stiffness.

Purpose
The goal of this study was to study the change in retinal microvascular dysfunction, brachial artery endothelial function and arterial stiffness in high-risk cardiovascular risk patients before and after initiation of PCSK9 inhibitor therapy with alirocumab or evolocumab.

Methods
In this prospective observational study, cardiovascular high-risk patients with a clinical indication for PCSK9 inhibitors were included for the measurement of retinal microvascular function (flicker light-induced dilatation of retinal arterioles and venules, FIDart and FIDven respectively; retinal arteriovenous ratio, AVR), brachial artery flow-mediated dilatation (FMD) and arterial stiffness (pulse wave velocity, PWV; augmentation index, AI). Measurements were performed at baseline, after 3 months and after 12 months of PCSK9 inhibitor therapy. The primary endpoint was the change in FIDart after 12 months of therapy compared to baseline.

Results
We recruited 48 patients (mean age 57±11 years, 27% female, 81% coronary artery disease) which began treatment with alirocumab or evolocumab in our lipid outpatient clinic. 6 patients were excluded from the analysis (n=3 stopped due to side effects, n=1 stopped due to new metastatic cancer, n=1 moved abroad, n=1 no retinal vessel analysis possible). LDL cholesterol was reduced from 3.8±1.2 to 1.5±0.8 and 1.8±0.9 mmol/L at 3 and 12 months respectively (all p&lt;0.001). There was no significant change in systolic blood pressure during therapy. The primary endpoint FIDart was significantly increased after 12 months of PCSK9 inhibitor therapy compared to baseline (3.4±2.3 vs. 2.6±1.6%, p=0.01). Among the secondary endpoints, augmentation index improved at 12 months vs. baseline (21±12 vs. 24±9%, p=0.03). No significant change was seen for FIDven, AVR, FMD and PWV after 3 and 12 months of therapy.

Conclusion
In cardiovascular high-risk patients, PCSK9 inhibition is associated with an improvement of retinal microvascular function and augmentation index after one year of therapy. No effects were seen for macrovascular parameters such as FMD or PWV in our cohort.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): University Hospital Zurich, AGLA Grant (sponsored by Amgen)
Acetyl-CoA carboxylase inhibition alters tubulin acetylation and aggregation in thrombin-stimulated platelets
Authors: Octave M , Pirotton L , Ginion A , Robaux V , Lepropre S , Kautbally S , Darley-Usmar V M , Ambroise J , Guigas B , Giera M , Foretz M , Bertrand L , Beauloye C , Horman S 
Published: October 2021

Abstract

Introduction
Acetyl-CoA carboxylase (ACC), the first enzyme regulating lipid synthesis, promotes thrombus formation by increasing platelet phospholipid content. Inhibition of its activity decreases lipogenesis and increases the content in acetyl-CoA which can serve as a substrate for protein acetylation. This posttranslational modification plays a key role in the regulation of platelet aggregation, via tubulin acetylation.

Purpose
To demonstrate that ACC inhibition may affect platelet functions via an alteration of lipid content and/or tubulin acetylation.

Methods
Platelets were treated 2 hours with CP640.186, a pharmacological ACC inhibitor, prior to thrombin stimulation. Platelet functions were assessed by aggregometry and flow cytometry. Lipogenesis was measured via 14C-acetate incorporation into lipids. Lipidomics analysis was carried out on the commercial Lipidyzer platform. Protein phosphorylation and acetylation were evaluated by western blot.

Results
Treatment with CP640.186 drastically decreased platelet lipogenesis. However, the quantitative lipidomics analyses showed that preincubation with the compound did not affect global platelet lipid content. Interestingly, this short-term ACC inhibition was sufficient to increase tubulin acetylation level, at basal state and after thrombin stimulation. It was associated with an impaired platelet aggregation, in response to low thrombin concentration, while granules secretion was not affected. Mechanistically, we highlighted a decrease in Rac1 activity, associated with a reduced phosphorylation of its downstream effector PAK2. Surprisingly, actin cytoskeleton was not impacted but we evidenced a significant decrease in ROS production which could result from a decreased NOX2 activity.

Conclusion
Pharmacological ACC inhibition decreases platelet aggregation upon thrombin stimulation. The mechanism depends on increased tubulin acetylation, with subsequent alteration of the Rac1/PAK2/NOX2 signaling pathway

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): Fonds pour la formation à la Recherche dans l'Industrie et l'Agriculture (FRIA)
Global magnitude and temporal trend of infective endocarditis, 1990–2019: results from the Global Burden of Disease Study
Authors: Yang Xiaorong , Chen Hui , Zhang Dandan , Shen Lin , An Guipeng , Zhao Shaohua 
Published: October 2021

Abstract

Aims
To estimate the spatiotemporal patterns in infective endocarditis (IE) burden along with its attributable risk factors at the national, regional, and global levels, which is essential to optimize the targeted prevention, clinical practice, and research.

Methods and results
Based on all available data sources, the incidence, mortality, and disability-adjusted life years (DALYs) of IE in 204 countries and regions from 1990 to 2019 were reconstructed by Global Burden of Disease Study 2019 using the Cause of Death Ensemble model, spatiotemporal Gaussian process regression, and DisMod-MR 2.1. We depicted the epidemiological characteristics of IE in detail by gender, region, and age. Globally, 1 090 527 incident cases, 66 322 deaths, and 1 723 594 DALYs of IE were estimated in 2019. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) increased from 9.91 and 0.73 to 13.80 and 0.87 per 100 000 person-years over the past 30 years, respectively. ASIR were consistently more pronounced in higher socio-demographic index (SDI) regions. The leading ASMR in 2019 appeared in the High SDI region, with the largest increase in the past three decades. The age-specific burden rate of IE among people over 25 years old usually increased with age, and the annual increasing trend was more obvious for people over 60 years of age, especially in higher SDI regions.

Conclusion
The incidence and mortality of IE have continued to rise in the past 30 years, especially in higher SDI regions. The patient population was gradually shifting from the young to the elderly.