bluuebunny/crossref_metadata_2025_split huggingface dataset:
5035Comparative assessment of diagnostic algorithms of myocardial inflammation by endomyocardial biopsy and tissue mapping by CMR against high-sensitive troponin in viral myocarditis
Authors: Zainal Abidin H A , Klingel K , Rolf A , Keller T , Zhou H , Vasquez M , Escher F , Lassner D , Vasa-Nicotera M , Zeiher A , Schultheiss P , Nagel E , Puntmann V 
Published: October 2019

Abstract

Background
Myocarditis is defined by inflammatory involvement of the myocardium, either histologically by evidence of myocardial necrosis and cellular infiltration on endomyocardial biopsy (EMB), or non-invasively by presence of myocardial oedema using tissue mapping with cardiovascular magnetic resonance (CMR). Objective: to undertake intra-individual comparisons of EMB vs. CMR diagnostic algorithms of myocardial inflammation, as well as against an independent gold-standard of myocardial injury, high-sensitive troponin (hs-TropT).

Methods
Prospective multicentre study of consecutive patients (n=109) with clinical diagnosis of myocarditis. EMBs were analysed by 2 reference centres using the ESC diagnostic and their local algorithms. The CMR criteria used sequence-specific cut-offs for native T1 and T2 (standard deviation, SD); myocardial inflammation T1 ≥2SD, T2 ≥2SD and no inflammation: T1 and T2<2SD, with subcategories for acute/high-grade: T1 ≥5SD, T2 ≥2SD; chronic/low-grade: T1 ≥2SD, T2 ≥2SD; healed: T1 <2SD, T2 <2SD but myocardial impairment and non-inflammatory cardiomyopathy: T1 ≥2SD, T2 <2SD.

Results
The agreement between ESC criteria and CMR criteria (AUC: 0.56, p=0.381) was poor. There was a significant agreement between myocardial injury (hs-TropT ≥13.9 ng/L) and CMR criteria (AUC: 0.84, p<0.001), but not ESC algorithm. hs-TropT levels had significant associations with native T1 and T2 (r=0.37 and 0.35, p<0.001), but not with immunohistochemical inflammatory markers. Viral presence was similarly proportioned between inflammatory/non-inflammatory subjects, irrespective of the algorithm.
AUC of CMR and EMB versus hs-TroponinT

Conclusions
Poor agreement between CMR and EMB-based diagnostic algorithms suggests non-overlapping definitions of myocardial inflammatory involvement. Excellent agreement between CMR algorithm and hs-TropT reiterates its high sensitivity for inflammatory myocardial injury.

Acknowledgement/Funding
1. National Institute for Health Research (NIHR) Biomedical Research Centre 2. German Centre for Cardiovascular Research (DZHK)
5106A pattern-discovery-based outcome predictive tool integrated with clinical data repository: design and a case study on contrast related acute kidney injury
Authors: Li Y X , Jiang J , Zhang Y , Li J P , Huo Y 
Published: October 2019

Abstract

Introduction
Clinical data repositories (CDR) including electronic health record (EHR) data have great potential for outcome prediction and risk modeling. However, most CDRs were only used for data displaying, and using data from CDR for outcome prediction often requires careful study design and sophisticated modeling techniques before a hypothesis can be tested.

Purpose
We built a prediction tool integrated with CDR based on pattern discovery aiming to bridge the above gap and demonstrated a case study on contrast related acute kidney injury (AKI) with the system.

Methods
A cardiovascular CDR integrated with multiple hospital informatics systems was established. For the case study on AKI, we included patients undergoing cardiac catheterization from January 13, 2015 to April 27, 2017, excluding those with dialysis, end-stage renal disease, renal transplant, and missing pre- or post-procedural creatinine. To handle missing data, a prior-history-note composer was designed to fill in structured data of 14 diseases related to cardiovascular problem. Crucial data such as ejective fraction was extracted from the structured reports. AKI was defined according to Acute Kidney Injury Network by increase of serum creatinine from most recent baseline to the post-procedure 7-day peak. To build predictive modeling, we selected 17 variables covered in existing AKI models. Pattern discovery was recently developed as an interpretable predictive model which works on incomplete noisy data. In this study, we developed a pattern discovery based visual analytics tool, and trained it on 70% data up to August 2016 with three interactive knowledge incorporation modes to develop 3 models: 1) pure data-driven, 2) domain knowledge, and 3) clinician-interactive. In last two modes, a physician using the visual analytics could change the variables and further refine the model, respectively. We tested and compared it with other models on the 30% consecutive patients dated afterwards, which is shown in Figure 1.

Results
Among 2,560 patients in the final dataset with 17 pre-procedure variables derived from CDR data, 169 (7.3%) had AKI. We measured 4 existing models, whose areas under curves (AUCs) of receiver operating characteristics curve for the test set were 0.70 (Mehran's), 0.72 (Chen's), 0.67 (Gao's) and 0.62 (AGEF), respectively. A pure data-driven machine learning method achieves AUC of 0.72 (Easy Ensemble). The AUCs of our 3 models are 0.77, 0.80, 0.82, respectively, with the last being top where physician knowledge is incorporated.
Demo and demonstration

Conclusions
We developed a novel pattern-discovery-based outcome prediction tool integrated with CDR and purely using EHR data. On the case of predicting contrast related AKI, the tool showed user-friendliness by physicians, and demonstrated a competitive performance in comparison with the state-of-the-art models.
5192Management and outcomes of patients with unstable angina with undetectable, normal, or intermediate hsTnT levels - A RAPID CPU substudy
Authors: Biener M , Giannitsis E , Hund H , Mueller-Hennessen M , Vafaie M , Gandowitz J , Riedle C , Loehr J , Katus H A , Stoyanov K M 
Published: October 2019

Abstract

Background
Patients with unstable angina (UA) are regarded to be at low risk for future coronary events. Guidelines discourage routine coronary angiography and recommend early discharge after individualized risk stratification. The relative value of clinical risk indicators as compared to cardiac troponin (cTn) alone is unsettled in the era of high-sensitivity cardiac troponin (hsTn) assays.

Purpose
We aimed to investigate the clinical characteristics, therapies and outcomes of UA patients with different hsTnT concentrations.

Methods
During 12 months, 2,525 patients were enrolled. UA was defined as unstable symptoms and either undetectable (<5 ng/L), normal (5–14 ng/L) or stable elevated hsTnT (15–51 ng/L). Follow up for 1-year mortality was available in 98.7%.

Results
A total of 280 patients (11.1%) received a diagnosis of UA. Mortality rates at 12 months were 0%, 1.9% and 6.9% in presence of undetectable, normal and stable elevated hsTnT. Elevated hsTnT >99th percentile but not unstable symptoms carried an independent 3.25-fold (1.78–5.93) higher risk for all-cause death after adjustment for other clinical risk indicators or the GRACE score. Utilization of guideline recommended therapies was high albeit lower than for non-ST-elevation myocardial infarction (NSTEMI). Significantly fewer patients with UA received dual antiplatelet therapy (DAPT, odds ratio (OR): 0.51 [95% CI: 0.44–0.59], p<0.0001), coronary angiography (CA, OR 0.79, [95% CI: 0.74–0.87], p<0.0001), and percutaneous coronary intervention (PCI, OR 0.50, [95% CI: 0.40–0.61], p<0.0001), compared to NSTEMI. However, prevalence of significant obstructive coronary artery disease (CAD) requiring PCI was 31.8%, even in patients with undetectable hsTnT, indicating the need for stress testing.

Conclusions
The current dichotomization of patients into UA and NSTEMI is no longer appropriate. Additional risk stratification seems warranted including the presence and magnitude of hsTn concentration and additional risk indicators.

Acknowledgement/Funding
Research Grant by Roche Diagnostics
5198HbA1C correlates subclinical atherosclerosis in non-diabetes
Authors: Wang W.-T , Hsu P.-F , Wang Y.-J , Ding Y.-Z , Liou T.-L , Wang Y.-W , Huang S.-S , Lu T.-M , Huang P.-H , Chen J.-W , Leu H.-B , Chan W.-L , Lin S.-J 
Published: October 2019

Abstract

Objective
We investigated the association of lipid parameters and coronary atherosclerosis related to normal blood sugar (BS) and impaired fasting glucose (IFG), and factors contributing to coronary atherosclerosis.

Methods
We analyzed 1209 non-diabetic subjects who underwent coronary computed tomography angiography (CCTA). Atherosclerotic plaque pattern severity and patterns were evaluated based on serum glucose values. The association between low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) and plaque patterns in non-diabetic subjects were also analyzed.

Results
Non-diabetic subjects (age: 58.6±9.7 years; 861 male) were enrolled. Higher glucose levels were correlated with a higher prevalence of mixed plaque, significant (>50% stenosis) high-risk plaque, and calcified plaque in non-diabetic patients. Although serum LDL-C levels were mostly controlled by statin use, atherosclerotic plaques progressed, with increasing A1c values. Multivariate logistic regression analysis showed that age, male gender and A1C were independently associated with the presence of significant mixed plaques after considering BMI, blood pressure, renal function, lipid parameters, uric acid, and smoking habit.

Conclusions
Although decreasing HDL-C and increasing TG correlated with the presence and severity of coronary atherosclerosis, increasing A1c is independently associated with the presence of high-risk plaque in non-diabetes even if LDL-C is controlled by statin therapy.
5877Comorbidity assessment for mortality risk stratification in elderly patients with acute coronary syndrome
Authors: Soler Costa M , Nunez J , Ruiz V , Bonanad C , Formiga F , Valero E , Martinez Selles M , Marin F , Ruescas A , Garcia Blas S , Minana G , Abu-Assi E , Bueno H , Ariza-Sole A , Sanchis J 
Published: October 2019

Abstract

Background
The Charlson's is the most used comorbidity index. It comprises 19 comorbidities, some of which are infrequent in elderly patients with acute coronary syndrome (ACS), while some others are manifestations of cardiac disease rather than comorbidities.

Purpose
Our goal was to simplify comorbidity assessment in elderly non-ST-segment elevation ACS patients.

Methods
The study group consisted of 1 training (n=920, 76±7 years) and 1 testing (n=532; 84±4 years) cohorts. The end-point was all-cause mortality at 1-year follow-up. Comorbidities were assessed selecting those medical disorders other than cardiac disease that were independently associated with mortality by multivariable analysis.

Results
A total of 130 (14%) patients died in the training cohort. Six comorbidities were predictive: renal failure, anemia, diabetes, peripheral artery disease, cerebrovascular disease and chronic lung disease. The increase in the number of comorbidities yielded a gradient of risk on top of well-known clinical predictors: ≥3 comorbidities (27% mortality, HR=1.90, 95% CI 1.20–3.03, p=0.006); 2 comorbidities (16% mortality, HR=1.29, 95% CI 0.81–2.04, p=0.30); and 0–1 comorbidities (7.6% mortality, reference category). The discrimination accuracy (C-statistic= 0.80) and calibration (Hosmer-Lemeshow test, p=0.20) of the predictive model using the 6 comorbidities was comparable to the predictive model using the Charlson index (C-statistic=0.80; Hosmer-Lemeshow test, p=0.70). Similar results were reproduced in the testing cohort (≥3 comorbidities: 24% mortality, HR=2.37, 95% CI 1.25–4.49, p=0.008; 2 comorbidities: 14% mortality, HR=1.59, 95% CI 0.82–3.07, p=0.20; 0–1 comorbidities: 7.5% reference category).
Kaplan-Meyer curves for mortality

Conclusion
A simplified comorbidity assessment comprising 6 comorbidities provides useful risk stratification in elderly patients with ACS

Acknowledgement/Funding
This work was supported by grants from Spain's Ministry of Economy and Competitiveness through the Carlos III Health Institute
5893Adipose tissue secreted ceramides and related sphingolipids - potential modulators of vascular redox signalling in cardiovascular disease
Authors: Akawi N , Checa A , Kotanidis C , Akoumianakis I , Daskalakis E , Herdamn L , Wheelock C , Antoniades C 
Published: October 2019

Abstract

Background
Adipose tissue (AT) plays a vital role in the modulation of vascular biology via known adipokines and other yet unidentified secreted molecules. Recent technological advances of omics-based approaches have enabled the identification of more metabolites that drive the currently recognised cross talk between the AT and the vasculature.

Purpose
The main aim of this study is to explore the role of AT secreted ceramides on the regulation of vascular superoxide (O2·−) generation in cardiac patients.

Methods
Untargeted metabolic profiling for the secretome of paired thoracic and subcutaneous ATs from 48 patients undergoing cardiac surgery (the Oxford cohort for heart, vessels and fat) along with the subsequent sphingolipids-targeted quantification were performed using liquid-chromatography/mass-spectrometry. Immortalized human aortic endothelial cells (teloHAEC) were treated exogenously with C6-ceramide (CerC6) for 20min and O2·− production was measured using lucigenin-enhanced chemiluminescence.

Results
Metabolomics differential (A) and enrichment analysis (not shown) highlighted the significant differences in sphingolipids secretion levels between the two fat depots. Higher amount of ceramides were produced and secreted from the thoracic depot with C16-ceramide (CerC16) representing the most abundant differentially secreted ceramide (B). Compared to the lowest tertile, the middle and highest tertiles of ceramides in thoracic AT were significantly associated with higher O2·− generation in patients' vessels namely saphenous veins (SV) and internal mammary arteries (IMA) (C). Exogenous treatment of teloHAEC with ceramide increased O2·− generation and eNOS uncoupling evidenced by more negative O2·− after addition of L-NAME, an inhibitor of eNOS (D).
Results Overview

Conclusions
In this study, we demonstrate for the first time that sphingolipids, in particular ceramides, secreted from AT of cardiac patients may modulate their vascular redox state via dysregulating vascular eNOS signalling leading to endothelial dysfunction –a hallmark of cardiovascular disease.

Acknowledgement/Funding
the NovoNordisk Foundation (NNF15CC0018486)
6112Usefulness of the trans-stent fractional flow reserve gradient for predicting clinical outcomes
Authors: Lim H , Yang H M , Yoon M H , Seo K W , Choi B J , Choi S Y , Seo J Y , Jin U , Tahk S J 
Published: October 2019

Abstract

Aims
The clinical meaning of a trans-stent pressure gradient after DES implantation has not been estimated adequately. We evaluated the usefulness of a fractional flow reserve (FFR) gradient across the stent (ΔFFRstent) for long-term clinical outcomes after percutaneous coronary intervention (PCI) with a drug-eluting stent (DES).

Methods and results
FFR pull-back and intravascular ultrasound (IVUS) were performed after successful PCI in 135 left anterior descending artery lesions. ΔFFRstent was defined as the FFR gradient across the stent. The ΔFFRstent/length was defined as the ΔFFRstent value divided by the total stent length multiplied by 10 [= (ΔFFRstent ÷ stent length) x 10]. Major adverse cardiac events (MACEs) were the composite of all-cause death, target vessel related myocardial infarction, and target lesion revascularisation. Despite successful PCI without significant complications on IVUS, ΔFFRstent >0 was observed in 98.5% of cases. ΔFFRstent ≥0.04 and ΔFFRstent/length ≥0.009 predicted suboptimal stenting defined as final minimal stent area <5.5 mm2. During 2183±898 days, the MACE-free survival rate was significantly lower in patients with ΔFFRstent ≥0.04 and ΔFFRstent/length ≥0.009 compared to those with lower values (69.6 vs. 93.4%, log-rank p=0.031; 72.1 vs. 97.7%, log-rank p=0.003, respectively). ΔFFRstent/length ≥0.009 (hazard ratio 10.1, p=0.032) was an independent predictor of MACE.
Trans-stent FFR and MACE

Conclusion
A trans-stent FFR gradient was frequently observed in DES-treated patients despite successful PCI results. ΔFFRstent and ΔFFRstent/length are useful indicators for optimising a DES and are related to long-term outcomes.
6123A novel ECG parameter predicts lack of eligibility for Subcutaneous Implantable Cardioverter Defibrillator (S-ICD) in patients with Brugada Syndrome
Authors: Mazzanti A , Marelli S , Chargeishvili T , Trancuccio A , Marino M , Bulian F , Monteforte N , Bloise R , Napolitano C , Priori S G 
Published: October 2019

Abstract

Background
A conclusive estimate of the eligibility rate for the use of subcutaneous implantable cardioverter defibrillators (S-ICD) in patients with Brugada Syndrome (BrS) is lacking.

Objective
We aimed to: 1) evaluate the eligibility for S-ICD in patients with BrS using a novel automated tool; 2) investigate predictors of ineligibility for S-ICD, based on baseline 12-lead electrocardiogram.

Methods
Automated screening for S-ICD was performed in 118 consecutive BrS patients using the programmer provided by the S-ICD producer. The system automatically assessed the acceptability of each of the three sense vectors used by the S-ICD for the detection of cardiac rhythm. Eligibility was defined when at least one vector was acceptable both in supine and standing position.

Results
The clinical characteristics of 118 BrS patients were as follow: age 43±11 years; 89% males; 2% with aborted cardiac arrest; 14% with a history of syncope; 81% with spontaneous type 1 ECG pattern; 21% with a familial history of sudden cardiac death; 24% with an SCN5A mutation. No patients had an indication for pacing. Only 8/118 (7%) patients were ineligible for S-ICD. Of note, 5/8 (63%) patients who failed the screening exhibited a slurred S wave of ≥80 ms duration in the peripheral lead aVF on the 12-lead baseline electrocardiogram, vs. 4/110 (4%) of those who passed the screening (sensitivity of S wave in aVF for screening failure 63%, specificity 97%; p<0.001). Remarkably, the presence of a slurred S wave of ≥80 ms duration in lead aVF remained significantly associated to the failure of eligibility for S-ICD (odds ratio 50, p<0.001) in a multivariable analysis that included the previous history of symptoms, the presence of a spontaneous type 1 ECG pattern, the gender and the presence of SCN5A mutations.
ECG predictor of S-ICD screening

Conclusion
Up to 93% of BrS patients are eligible for S-ICD when the automated screening tool is used. The presence of a slurred S wave in lead aVF on the 12-lead electrocardiogram is a powerful predictor of screening failure.
6127Maternal, fetal and obstetric outcome in patients with thoracic aortic disease: an ancillary analysis of the ROPAC registry
Authors: Campens L , Baris L , De Backer J , Roos-Hesselink J 
Published: October 2019

Abstract

Background
Cardiovascular disease is the leading cause of death during pregnancy with thoracic aortic dissection being one of the main causes. Thoracic aortic disease (TAD) is most commonly related to hereditary disorders and congenital heart malformations such as bicuspid aortic valve (BAV). Pregnancy is considered as a trigger for aortic complications in women with underlying aortic disease. With this analysis, we aim to study the maternal and fetal outcome of pregnancy in women with TAD.

Methods
The Registry Of Pregnancy And Cardiac disease (ROPAC) is a large, prospective and global registry and enrolled 4418 women from January 2011 onwards with known cardiac disease (mainly congenital and valvular disease) before pregnancy.

Results
TAD was present in 217 woman prior to pregnancy. Almost half of them were Marfan patients (MFS), 20% had a BAV, 7.4% Turner syndrome and 23% of patients had no underlying genetic defect or associated congenital heart defect. 35.5% of patients had aortic dilatation of which 6% had an aortic diameter above 45mm.
Half of patients had previous pregnancies with no significant difference in parity between woman with and without aortic dilatation. Four patients of which 3 MFS patients had an acute aortic dissection (three type A and one type B aortic dissection) but no lethal (maternal of fetal) events occurred. Two patients presented with ventricular arrhythmia of whom one MFS patient. Caesarian section was not performed significantly more frequent in patients with aortic dilatation. Birth weight was lower in the group of woman with aortic dilatation, related to the use of beta-blocking agents. However, intra-uterine growth retardation and prematurity did not occur more frequently.

Conclusion
This ancillary analysis of the ROPAC data provides the first large prospective data on pregnancy risk of patients with a wide range of TAD.
MFS patients are highly represented in the registry and are a vulnerable group to develop severe complications during pregnancy or peripartum with occurrence of aortic dissection in 3% of patients and ventricular arrhythmia in one. Serial follow-up by a specialized multidisciplinary team throughout pregnancy and postpartum period and patient tailored management of delivery is advised.
P4995Neuregulin-1 compensates for endothelial NO synthase deficiency in the heart and kidney
Authors: Shakeri H , De Moudt S , Leloup A J , Jacobs G , De Meyer G R Y , De Keulenaer G W , Fransen P , Guns P.-J.F , Segers V F 
Published: October 2019

Abstract

Background
Decreased eNOS activity is the hallmark of endothelial dysfunction and is associated with cardiovascular and renal disorders. Besides NO, endothelial cells produce numerous other small molecules, peptides, and proteins, which modulate the function of adjacent cells. For instance, neuregulin-1 (NRG-1) is an endothelium-derived growth factor, which plays crucial roles in cardiovascular development, has cardioprotective properties, and induces growth and differentiation of cell types in different organs, including the kidney.

Purpose
Although the cardioprotective effects of endothelium-derived NO and NRG-1 are well established, their interaction is not clear. Therefore, we studied the interaction between the NO/eNOS and NRG-1/ErbB signalling pathways in a transgenic eNOS knock-out mouse model (eNOS−/−) treated with subpressor doses of angiotensin II (AngII).

Methods
eNOS−/− mice and their wild type (WT) littermates (n=64, 15 weeks old) were randomized for implantation of osmotic minipumps with AngII (400 ng/kg.min) for 28 days or sham surgery. Mice were randomized to receive either daily NRG-1 injections (20 μg/kg, intraperitoneal) or vehicle for 4 weeks (n=8/group). Hypertrophy and fibrosis were measured in left ventricle (LV) and kidneys using echography and immunohistochemical staining.

Results
Although blood pressure was higher in eNOS−/− mice compared to their WT littermates, it was unaffected by a subpressor dose of AngII. Masson's trichrome staining showed that AngII significantly increased LV (interstitial and perivascular) and renal fibrosis in eNOS−/− mice, but not in WT controls (see figure for LV data). NRG-1 reversed this AngII-induced LV and renal fibrosis caused by eNOS deficiency. There was also significant hypertrophy of LV and kidneys in eNOS−/− mice treated with AngII, which was again normalized by NRG-1 treatment. Moreover, NRG-1 significantly attenuated albuminuria induced by eNOS deficiency under AngII treatment.

Conclusions
This study demonstrates that the anti-fibrotic and anti-hypertrophic effects of NRG-1 are independent from the NO/eNOS pathway in both heart and kidney. Strikingly, NRG-1 is able to compensate for some of the negative effects of eNOS deficiency, at least in conditions of AngII stimulation.

Acknowledgement/Funding
supported by university of Antwerp