bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cost effectiveness study into the detection of functionally significant coronary artery disease in patients with chronic coronary syndrome: a decision-analytic modelling approach
Authors: Nazir M.S , Rodriguez-Guadarrama Y , Rua T , Chiribiri A , Pennington M , Plein S 
Published: November 2020

Abstract

Background
ESC guidelines recommend functional or anatomical imaging for stable coronary artery disease (CAD) diagnosis. We investigated cost-effective diagnostic strategies for CAD detection with invasive coronary angiography (ICA) and fractional flow reserve (FFR) as reference standard [1,2], using NHS reference costs.

Methods
Deterministic and probabilistic decision-analytic models for diagnostic strategies in low (25%), intermediate (50%) and high (75%) risk CAD were devised. Strategies: standalone or combined testing with computed tomographic coronary angiography (CTCA), stress echocardiography (SE), CT-FFR, single-photon emission computed tomography (SPECT), cardiac magnetic resonance (CMR), positron emission tomography (PET), ICA, and ICA-FFR. Proportion of correct diagnosis served as measure of clinical effectiveness. Incremental cost-effectiveness ratios were calculated for dominant strategies. Cost-effectiveness acceptability curves (CEAC) tested variation of cost-effectiveness threshold (CET).

Results
Base case (Table 1) consistent with probabilistic analysis (Figure 1 left). CEACs (Figure 1 right).

Conclusions
Direct ICA is not cost-effective. Functional testing has significant role in low/intermediate risk. CMR is cost-effective in all risk and most likely cost-effective in CETs &lt;£10,000. ICA-FFR yields highest correct diagnoses in all at highest cost. Future long-term follow-up studies with quality of life measures are needed.

References
1. Knuuti et al EHJ. 2018; 39(35):3322–30
2. Danad et al. EHJ. 2016; 38(13):991–8.
Figure 1. A: low, B: intermediate, C: high.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): The authors acknowledge financial support from the Department of Health through the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust and by the NIHR MedTech Co-operative for Cardiovascular Disease at Guy's and St Thomas' NHS Foundation Trust. This abstract presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0416-20008). This work was supported by the Wellcome/EPSRC Centre for Medical Engineering [WT 203148/Z/16/Z]. MSN was funded by the UK Medical Research Council under grant number MR/P01979X/1. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care, EPSRC, MRC or the Wellcome Trust.
Left ventricular hypertrophy detection system based on electrocardiogram signal
Authors: Liu C.W , Pan R.H , Hu Y.L 
Published: November 2020

Abstract

Background
Left ventricular hypertrophy (LVH) is associated with increased risks of cardiovascular diseases. Electrocardiography (ECG) is generally used to screen LVH in general population and electrocardiographic LVH is further confirmed by transthoracic echocardiography (Echo).

Purpose
We aimed to establish an ECG LVH detection system that was validated by echo LVH.

Methods
We collected the data of ECGs and Echo from the previous database. The voltage of R- and S-amplitude in each ECG lead were measured twice by a study assistance blinded to the study design, (artificially measured). Another knowledge engineer analyzed row signals of ECG (the algorithm). We firstly check the correlation of R- and S-amplitude between the artificially measured and the algorythm. ECG LVH is defined by the voltage criteria and Echo LVH is defined by LV mass index &gt;115 g/m2 in men and &gt;95 g/m2 in women. Then we use decision tree, k-means, and back propagation neural network (BPNN) with or without heart beat segmentation to establish a rapid and accurate LVH detection system. The ratio of training set to test set was 7:3.

Results
The study consisted of a sample size of 953 individuals (90% male) with 173 Echo LVH. The R- and S-amplitude were highly correlated between artificially measured and the algorithm R- and S-amplitude regarding that the Pearson correlation coefficient were &gt;0.9 in each lead (the highest r of 0.997 in RV5 and the lowest r of 0.904 in aVR). Without heart beat segmentation, the accuracy of decision tree, k-means, and BPNN to predict echo LVH were 0.74, 0.73 and 0.51, respectively. With heart beat segmentation, the signal of Echo LVH expanded to 1466, and the accuracy to predict ECG LVH were obviously improved (0.92 for decision tree, 0.96 for k-means, and 0.59 for BPNN).

Conclusions
Our study showed that machine-learning model by BPNN had the highest accuracy than decision trees and k-means based on ECG R- and S-amplitude signal analyses.
Figure 1. Three layers of the decision tree

Funding Acknowledgement
Type of funding source: None
Patient consent in emergency cardiovascular medicine: lessons from the ARREST trial in out-of-hospital cardiac arrest
Authors: Perkins A , Patterson T , Evans R , Clayton T , Fothergill R , Redwood S 
Published: November 2020

Abstract

Introduction
Randomised trials in emergency cardiovascular medicine are challenging but vital for improving patient care. Obtaining informed consent in such an environment is a particular issue and can be controversial. The ARREST trial is assessing whether out-of-hospital cardiac arrest patients without an obvious cause should be taken to a specialist heart centre or the closest emergency department in London, UK. This patient group presents specific difficulties: patients lack capacity to consent, presentation is unpredictable, care must not be delayed, and mortality rates can be &gt;50%.

Purpose
Within existing consent and methodological frameworks we aimed to design a randomised clinical trial to pragmatically, safely and ethically recruit cardiac arrest patients pre-hospital.

Methods
During the set-up of ARREST we accessed the following sources of information: 1) ARREST research team; 2) cardiovascular patient groups; 3) researchers running similar trials; 4) regulatory bodies; and, 5) published literature on research in emergency contexts. The information that we collected guided the design of the trial with a focus on patient consent, documentation and follow-up.

Results
The ARREST trial uses deferred consent with remote online randomisation to enrol patients without delaying care. To minimise the risk of bias, baseline and primary endpoint data are collected on patients who die or are discharged prior to consent. Remote follow-up using electronic health records reduces the burden on the patients and researchers. Full ethical approval was received in January 2018 and the first patient was enrolled in February 2018. ARREST is recruiting to target and is on track to finish within the projected timelines.

Conclusions
Deferred consent has been key to the success of ARREST and patients have been receptive. However, further research into the experience of patients in emergency cardiovascular medicine trials using deferred consent is needed to better understand when it is an appropriate model. More broadly, there is a shortfall in high quality research in challenging environments such as emergency cardiovascular care. Innovation in consent methods and proportional research governance would facilitate higher quality research and benefit patient care.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): British Heart Foundation
Simultaneous endo-epicardial mapping of the human sinus node in patients undergoing cardiac surgery
Authors: Kharbanda R , Wesselius F.J , Taverne Y.J.H.J , Kik C , Van Schaagen F.R.N , Roos-Serote M.C , Bogers A.J.J.C , De Groot N.M.S 
Published: November 2020

Abstract

Introduction
Conduction disorders in the right atrium (RA) are predominantly observed in the superior part. Presence of the sinoatrial node (SAN) in this region could be contributing to increased heterogeneity in activation patterns. However, mapping studies focusing on SAN activation are scarce.

Purpose
The aim of the present study was to analyze activation patterns of the human SAN during sinus rhythm.

Methods
A dataset containing simultaneous endo-epicardial mapping data (256 electrodes, inter-electrode spacing: 2mm) of RA was screened for focal activation patterns (FAPs) potentially arising from SAN activation (SN-FAP). Conduction time, endo-epicardial delay and electrogram morphology (R/S-ratio) were described in the surrounding 1cm of SN-FAPs. Areas of conduction block (CB) were defined as conduction delays of ≥12ms and endo-epicardial asynchrony (EEA) as activation time differences of exact opposite electrodes of ≥15ms.

Results
In 20 patients (75% male, 66±7 years) a total of 28 SN-FAPs with unique activation patterns were observed only in superior RA (n=22) and mid RA (n=6). Conduction velocity of SN-FAPs was 1.3m/s [0.8–2.5] and percentage of EEA was 5% [2–18]. Conduction velocity was lower when lines of CB were present within 6mm of the SN-FAPs (p=0.040). Significantly larger R-peaks were observed in mid RA compared to superior RA. (mid R/S-ratio:0.15 [0.067–0.34] vs. superior R/S-ratio:0.045 [0.026–0.062], p=0.004).

Conclusions
Conduction velocities around the SAN area are comparable to the remainder of the atria. SN-FAPs occurred in both superior and mid RA, suggesting presence of multiple exit sites of the SAN. Furthermore, inter-individual differences in rS-morphology indicate that SAN activation may originate from multiple layers within the atrial wall.

Funding Acknowledgement
Type of funding source: None
Membrin/GOSR2 is a novel NaV1.5-interacting protein modulating cardiac conduction
Authors: Offerhaus J , Podliesna S , Verkerk A.O , Marchal G , Lodder L.E , Boukens B.J.B , Remme C.A , Bezzina C.R 
Published: November 2020

Abstract

Background
Genome-wide association studies have associated a locus spanning GOSR2 with QRS- and QT-interval. GOSR2 encodes Membrin, a protein located at the cis-Golgi, which plays a role in protein trafficking. Altered trafficking of the cardiac sodium channel (NaV1.5), encoded by SCN5A, has been shown to reduce cardiac conduction.

Purpose
To explore the modulatory role of Membrin on cardiac conduction and sodium channel availability.

Methods and results
Tandem Affinity Purification in H10 cells (derived from neonatal rat cardiomyocytes) overexpressing the NaV1.5 C-terminus identified Membrin as a putative interactor of NaV1.5. We subsequently confirmed the interaction between NaV1.5 and Membrin by means of a co-immunoprecipitation assay in HEK293A cells that overexpress NaV1.5 and Membrin.
To investigate whether Membrin affects cardiac conduction we recorded optical action potentials from the left ventricle (LV) of Langendorff-perfused hearts from Gosr2+/− mice and wild type (WT) littermate controls. Conduction velocity was measured at steady state pacing (cycle length 120ms) and at the minimal possible cycle length (S2min), during S1S2 pacing. Longitudinal conduction velocity was increased in Gosr2+/− mice compared to WT at steady state- (76.44 vs. 67.00 cm/s) as well as at S2min (62.00 vs. 51.86 cm/s, p=0.039, n=10 and 9, resp.). Single cell patch-clamp studies revealed a shortened action potential duration at 90% repolarization at all pacing frequencies (390 vs 342 V/s at 2Hz, p=0.036) in isolated mid-LV cardiomyocytes of Gosr2+/− mice compared to WT. In addition, the maximal upstroke velocity was increased in Gosr2+/− mid-LV cardiomyocytes at frequencies of 6Hz and higher (390 vs 342 V/s at 6Hz, p=0.044).

Conclusion
Our findings identify Membrin as a novel interacting protein of NaV1.5 and a modulator of cardiac conduction. We propose that Membrin acts through ion channel trafficking or by modulating the posttranslational maturation of ion channels.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Leducq foundation
Ataxia-telangiectasia mutated protein protects cardiac cells from stress by rewiring glucose metabolism
Authors: Paolillo R 
Published: November 2020

Abstract

Introduction
Pressure overload-induced cardiac hypertrophy is associated with increased reactive oxygen species (ROS), inducing DNA damage and activating the protein kinase Ataxia-Telangiectasia Mutated (ATM). Recently, ATM has been also involved in the regulation of several metabolic processes, but whether and how it affects cardiac metabolism is still poorly understood.

Purpose
We hypothesized that ATM might play crucial roles in the maintenance of cardiomyocyte metabolic homeostasis and in the development of cardiac dysfunction in response to pressure overload.

Methods
Atm+/+ and Atm homozygous mutated mice (Atm−/−) underwent transverse aortic constriction (TAC) or sham operation (sham). After one week (1w), sham and TAC mice were anesthetized, cardiac function and morphometry were analyzed, and gene expression reprogramming, cardiac histology, mitochondrial morphology were performed. Metabolic profiling was carried out through untargeted metabolomics (LC-MS/MS and GC/MS), mRNA and/or protein levels analysis to investigate glycolyis, pyruvate oxidation, Krebs cycle, aminoacid synthesis, gluconeogenesis and lipid oxidation.

Results
Atm genetic inactivation induced cardiomyocytes hypertrophy and fetal gene reprogramming in sham mice, with normal cardiac function and in the absence of fibrosis or mitochondrial dysfunction (Figure 1A). After TAC 1w, cardiac function was significantly decreased in Atm−/− mice, compared to Atm+/+ (Figure 1B). In both sham and TAC 1w Atm−/− mice, significant metabolic abnormalities were identified, including switching of glycolysis, reduction of pyruvate oxidation (Figure 1B), activation of aminoacid synthesis and accumulation of long and short-chain fatty acid conjugated with carnitine. Pyruvate accumulation was associated to a significant reduction of pyruvate carrier (MPC1-MPC2) and pyruvate dehydrogenase (PDH) levels in sham and TAC 1w Atm−/− mice.

Conclusions
ATM regulates gene expression, cardiomyocyte hypertrophy and cardiac responses to pressure overload, modulating cardiac metabolism and the profile of intracellular substrate utilization in the heart. Thus, ATM might represent a novel important player in the development of cardiac dysfunction and a novel therapeutic target.
Figure 1

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): CP was supported by Ministero dell'Istruzione, Università e Ricerca Scientifica grant (2015583WMX) and Programma STAR grant by Federico II University and Compagnia di San Paolo. RP was supported by a research grant provided by the Cardiopath PhD program.
Mimetic nanoparticles regulate the inflammation of ischemic myocardium
Authors: Chen J , Huang Z.Y , Ge J.B 
Published: November 2020

Abstract

Background
Most drug delivery systems are lack of accurate targets, so the poor efficiency significantly limited the therapeutic effects. Neutrophil plays an important role in the acute phase of myocardial infarction. There are multiple chemokine receptors on the surface of cell membrane proteins, which participate in inflammatory chemotaxis and immune regulation.

Purpose
Through syntheses and target delivery of biomimetic neutrophil liposomes (Neu-Lipos), it is possible to increase the delivery efficiency, reduce inflammation of ischemic region and promote the progression of myocardium repair.

Methods and results
Biomimetic nanoparticles (Neu-Lipos) were synthesized using membrane proteins purified from activated neutrophils. Neu-Lipos were characterized using dynamic light scattering and were found to have a diameter of 163.5±3.6 nm, a surface charge of −28.7±1.6 mV. For in vivo studies, C57 mice were constructed of ischemia-reperfusion model. Mice were injected with either PBS, Lipos (5 mg/kg), or Neu-Lipos (5 mg/kg) one day after reperfusion. The targeting ability of Neu-Lipos to injured myocardium was significantly higher than Lipos. In mice treated with Neu-Lipo, the result of immunofluorescence revealed fewer M1 and more M2 infiltrating in border region compared with untreated mice and Lipo treated mice. Furthermore, macrophage polarization correlated with downward trends Inflammatory chemokines. Neu-Lipos–treated mice also displayed significantly decreased IL-1α, IL-1β and IL-6 in the injured myocardium. Histological analysis showed no significant toxicological alterations displayed in lung, spleen, kidney, or liver in Neu-Lipos treated group.

Conclusions
We showed that our Neu-Lipos showed a decrease in proliferating macrophage population that was accompanied by the reduction of key proinflammatory cytokines and changes in myocardial repair. This proof of concept showed that our platform was capable of altering macrophage polariton within the injured tissue after treated and with a favorable toxicity profile. This treatment could be a promising intervention for the acute ischemia of myocardium.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): The National Natural Science Foundation of China
DNMT3A clonal hematopoiesis-driver mutations are associated with profound changes in monocyte and T cell signatures in humans with heart failure
Authors: Abplanalp W , Cremer C , Cremer S , John D , John D , Hoffmann J , Hoffmann J , Rieger M.A , Rieger M.A , Vasa-Nicotera M , Vasa-Nicotera M , Zeiher A.M , Zeiher A.M , Dimmeler S , Dimmeler S 
Published: November 2020

Abstract

Background
Clonal hematopoiesis (CH) driven by mutations of DNA methyltransferase 3a (DNMT3A) is associated with increased incidence of cardiovascular disease and poor prognosis of patients with chronic heart failure (HF) and aortic stenosis. Although experimental studies suggest that DNMT3A CH-driver mutations may enhance inflammation, specific signatures of inflammatory cells in humans are missing. Single-cell RNA-sequencing provides a novel opportunity to define subsets of immune cells mediating inflammation in humans.

Methods
Transcriptomic profiles of peripheral blood mononuclear cells were analysed in N=6 HF patients harboring DNMT3A CH-drived mutations and with HF and N=5 patients with HF and DNMT3A mutations by single-cell RNA-sequencing.

Results
Monocytes of HF patients carrying DNMT3A mutations demonstrated a significantly increased expression of inflammatory genes compared to monocytes derived from patients with HF without DNMT3A mutations. Among the specific up-regulated genes were the prototypic inflammatory interleukins (IL) IL1B, IL6, and IL8, the macrophage inflammatory proteins CCL3 and CCL4 as well as restin, which augments monocyte-endothelial adhesion. The classical monocyte subset of DNMT3A mutation carriers showed increased expression of immunoglobulin superfamily members CD80, CD300LB, and SIGLEC12, as well as the cell adhesion molecule CD58, all of which may be involved in monocyte-T cell interactions. DNMT3A mutation carriers were further characterized by increased expression of T cell receptor chains and Th1, Th17, CD8+ and Treg specific signatures.

Conclusions
This study demonstrates that circulating monocytes and T cells of HF patients harboring CHIP-driver mutations in DNMT3A exhibit a highly inflamed transcriptome, which may contribute to the aggravation of chronic heart failure.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): The German Research Foundation (SFB834, Project B1), and the German Center for Cardiovascular Research (DZHK).
Genome-wide association study based on cardiac magnetic resonance imaging in 23,634 individuals identifies five new loci associated with left atrial enlargement
Authors: Ahlberg G , Andreasen L , Ghouse J , Haunsoe S , Svendsen J.H , Olesen M.S 
Published: November 2020

Abstract

Left atrial enlargement is associated with mortality due to cardiovascular disease and all-cause mortality. The pathology behind and the association with cardiovascular outcomes are, however, poorly characterised. Compromised atrial function seems to predispose for stroke.
We obtained data from the UK Biobank cardiovascular magnetic resonance (CMR) protocol containing CMR scans from ∼31,000 individuals at the time of study (Fig. 1a). Genome-wide association studies were carried out on state-of-the-art imaging variables exposed to machine learning algorithms to investigate the genetic basis of left atrial volume and function. Deep learning algorithms segmented the atria in the CMR scans (Fig. 1b). Left atrial (LA) volume curves could then be extracted and analysed (Fig. 1c).
We tested 10.6 million variants for association with LA minimum/maximum volumes and LA emptying fraction (LAEF) in 23,624 European individuals without prevalent myocardial infarction or heart failure. We identified five genetic loci located in close proximity to the genes EIF2D, C9orf3, ANKRD1, FGFR2, and MYO18B. We observed a notable genetic correlation between both maximum and minimum LA volumes and stroke and cardioembolic stroke (Fig. 1d).

Conclusions
We report on five genetic loci and suggest several plausible candidate genes important for atrial structural pathology. Genetic correlation analyses indicate that the genetic determinants of LA volumes could be markers of stroke risk. These findings enhance our understanding of the importance of the LA and are potential novel therapeutic targets for cardiovascular disease, including stroke.
Figure 1. LA imaging GWAS

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Novo Nordisk, Halles Moeller