bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4773Oral anticoagulants in patients with atrial fibrillation having an intermediate risk of ischemic stroke but a high risk of bleeding
Authors: Chao T F , Chen S A 
Published: October 2019

Abstract

Background
The use of oral anticoagulants (OACs) for patients with atrial fibrillation (AF) for stroke prevention should be balanced between the reduction on stroke risk and the increase in bleeding. Our aim was to investigate net clinical benefits of OACs among AF patients with a CHA2DS2-VASc score of 1 (males) or 2 (females) who had a HAS-BLED score ≥3.

Method
A total of 404,949 newly diagnosed AF patients were identified from the Taiwan National Health Insurance Research Database. The stroke risk was assessed using the CHA2DS2-VASc score and patients were classified as low (score 0 for males, 1 for females), intermediate (1 for males and 2 for females) and high risk (≥2 for males and ≥3 for females). A high risk of bleeding was defined as a HAS-BLED score ≥3.

Results
The CHA2DS2-VASc and HAS-BLED scores were significantly correlated (r=0.70). Around 72.7% of patients with a high-risk of stroke had a HAS-BLED score ≥3 (Figure A). Among patients with a CHA2DS2-VASc score of 1 (males) or 2 (females) who had a HAS-BLED score ≥3, the use of OACs was associated with a lower risk of adverse events (ischemic stroke, intra-cranial hemorrhage or mortality) with an adjusted hazard ratio of 0.781 (p=0.037) (Figure B).

Conclusion
Even among patients with an intermediate risk of ischemic stroke (CHA2DS2-VASc score 1 for males, 2 for females) having a high risk for bleeding (HAS-BLED score ≥3), use of OACs was associated with a better clinical outcome and should still be considered.
P4791Performance of the HAS-BLED, ATRIA, and PRECISE-DAPT Bleeding Risk Scores in Atrial Fibrillation Patients Using Antiplatelet Agents or Oral Anticoagulants
Authors: Choi S Y , Kim M H , Lee K M , Jang C H , Choi J Y 
Published: October 2019

Abstract

Background
Various bleeding risk scores have been proposed to assess the risk of bleeding in atrial fibrillation (AF) patients undergoing anticoagulation. PRECISE DAPT score has been developed to assess the out-of hospital bleeding risk in patients receiving dual antiplatelet therapy (DAPT). Our objective was to compare the predictive performance between the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly, Drugs/Alcohol), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and PRECISE-DAPT (Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet therapy) score in AF patients using antiplatelet agents or anticoagulants

Methods
We recruited 1,114 consecutive AF patients (51% male; median age, 71 years) receiving antiplatelet agents or oral anticoagulants from January 2014 through December 2018. Major bleeding was defined as according to the Bleeding Academic Research Consortium (BARC) criteria (type 3 or 5: hemodynamic instability, need for transfusion, drop in hemoglobin ≥3 g, and intracranial, intraocular or fatal bleeding). The performance of risk scores were assessed by C-statistic.

Results
Bleeding events occurred in 135 patients (12.1%) during 30 days, and 72 patients (6.5%) from 30 days till 1-year follow-up. Based on the C-statistic, PRECISE-DAPT score (AUC: 0.72, 95% CI: 0.69–0.75) had a good performance, significantly better than HAS-BLED (AUC: 0.64, 95% CI: 0.61–0.67) (p=0.008) or ATRIA scores (AUC: 0.57, 95% CI: 0.54–0.60) (p<0.001) for 30-days bleeding prediction. Also, PRECISE-DAPT score had a good C-statistic (AUC: 0.72, 95% CI: 0.69–0.75) for 1-year bleeding events compared with HAS-BLED (AUC: 0.64, 95% CI: 0.60–0.67) (p=0.02) or ATRIA (AUC: 0.61, 95% CI: 0.58–0.65) (p=0.01).
ROC curve for bleeding

Conclusions
The PRECISE-DAPT score has been used for assessing bleeding events during DAPT. Also, the PRECISE-DAPT score predicted bleedings better than HAS-BLED or ATRIA scores in AF patients. So, the PRECISE-DAPT score may be considered as bleeding risk score during DAPT or oral anticoagulation in clinical practice.
P4793Comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in the elderly Asian patients with atrial fibrillation
Authors: Chao T F , Liao J N , Lip G Y H , Chen S A 
Published: October 2019

Abstract

Background
Stroke prevention in elderly patients with atrial fibrillation (AF) can be challenging. Comparisons of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in the elderly, at different age strata (age 65–74, 75–89, ≥90) in the daily practice have not been well described, particularly in Asians. We aimed to assess the clinical outcomes of NOACs compared warfarin for stroke prevention in elderly patients with AF.

Methods
A total of 64,169 AF patients aged ≥65 years receiving NOACs or warfarin prescription were identified from the Taiwan National Health Insurance Research Database. The risks of adverse events were compared between NOACs and warfarin in all patients age ≥65 and specifically, with different age strata; that is 65–74 years, 75–89 years and >90 years.

Results
Overall NOACs were associated with a significantly lower risk of ischemic stroke (adjusted hazard ratio [aHR] 0.869, 95% confidence interval [CI] 0.812–0.931), ICH (aHR 0.524, 95% CI 0.456–0.601), major bleeding (aHR 0,824, 95% CI 0.776–0.875), mortality (aHR 0.511, 95% CI 0.491–0.532) and composite adverse events (aHR 0.646, 95% CI 0.625–0.667) compared to warfarin. There was heterogeneity in treatment effect for NOACs versus warfarin in different age strata, but the results still favored NOACs even among the very elderly (>90 years). The absolute risk difference and reductions in ICH and composite adverse events with NOAC use were even greater among the elderly compared to warfarin (Figure).

Conclusions
Compared to warfarin, NOACs were associated with a significantly lower risk of adverse events, with heterogeneity in treatment effects among different age strata. Overall, the clear safety signal in favor of NOACs over warfarin was evident irrespective of age strata, being most marked in the most elderly.
4934Biventricular global and regional strain measured by cardiovascular magnetic resonance based tissue tracking
Authors: Qu Y , Buckert D , Ma G S , Rasche V 
Published: October 2019

Abstract

Background
CMR based tissue tracking (CMR-TT), considered as a novel modality, provides additional insight into left and right ventricular (LV/RV) mechanical function and deformation. The vendor-specific reference values of global and regional strains for volunteers without history of cardiovascular disease are necessary as an important step in clinical routine to help detect early abnormality.

Purpose
To determine the reference value of LV/RV multi-dimensional global and segmental strains and diagnostic specificity of global longitudinal peak strain (GLS). Biventricular global and segmental radial, circumferential and longitudinal systolic peak strains (GRS, GCS, GLS and SRS, SCS, SLS) of 150 healthy adults in three age subgroups (G20–40, G41–60 and G61–80) were derived by post-hoc imaging software in standard steady-state free precession cine images acquired at 1.5T. LV strains were calculated with three-dimensional (3D) CMR-TT in the modified AHA 16-segment model via a short-axis stack and long axis 2-, 3-, 4-chamber cine images, and RV strains were generated with 2D CMR-TT via 4-chamber cine images.

Results
The reference values of LV global peak strains resulted as 44.4±13.0% for GRS, −17.0±2.7% for GCS, and −15.4±2.3% for GLS, respectively. RV-GLS was measured as −24.9±5.1%. Global and segmental strains might differ between males and females. Females showed significant age-associated difference of LV global peak strains (P<0.05) as the opposite of males (Figure 1). Females also presented higher magnitude of LV global peak strains than males in the eldest group G61–80 (P<0.05). Unlike LV, no age-associated difference of RV-GLS was detected in both gender groups. However, females showed less negative RV-GLS than males in G20–40 and more negative RV-GLS than males older than 40 years old (P<0.05). The local discrepancy of biventricular SRS, SCS and SLS was observed. It seemed that LV mid-cavity played a more essential role on LV shortening (more negative SCS and SLS) than wall thickening (smaller SRS) compared with base and apex. RV basal and mid SLS, derived from segment 1–4, was more negative than apical SLS derived from segment 5–6. The specificity of LV- and RV-GLS cut-off value (mean value+1.96*standard deviation) generated from the vendor-, age- and gender-specific reference value in evaluating heart contractile function reached 97.3% and 94.7%, respectively.

Conclusions
Considering the vendor-, gender- and age-associated difference of biventricular global strains, specific reference values need to be established to facilitate the wide application of strain in clinical routine. Meanwhile, segmental strains are also fundamental for detecting local abnormality of myocardial deformation.
4941Machine learning based automated diagnosis of ischemic vs non-ischemic dilated cardiomyopathy using 3D myocardial deformation analysis
Authors: Lei L , Satriano A , Magyar-Ng M , Mikami Y , Kalmady S V , Hoehn B , Dykstra S , Heydari B , Flewitt J , Merchant N , Howarth A G , Lydell C P , Greiner R , Fine N M , White J A 
Published: October 2019

Abstract

Background
Late Gadolinium Enhancement (LGE) imaging is a reference standard technique for the differentiation of ischemic cardiomyopathy (ICM) from non-ischemic dilated cardiomyopathy (NIDCM) in patients with heart failure and reduced ejection fraction (HFrEF). 3D myocardial deformation analysis (3D-MDA) offers highly reproducible phenotypic assessments of regional architecture and function that may provide value for artificial-intelligence-assisted cardiomyopathy diagnosis without need for LGE imaging.

Purpose
In this study, we trained and validated a machine-learning-based model to enable automated diagnosis of ischemic versus non-ischemic dilated cardiomyopathy exclusively using regional patterns of deformation among patients otherwise matched by age, sex and global contractile dysfunction.

Methods
100 ICM and 100 NIDCM patients matched for age, sex, and LVEF underwent standard cine SSFP and LGE imaging. Patient diagnoses were established using a combination of clinical and LGE-based criteria. 3D-MDA was performed using validated software (GIUSEPPE) to compute regional 3D strain measures at each cardiac phase in both conventional and principal strain directions. Principal Component Analysis (PCA) was performed on the composite 3D-MDA dataset. The first 20 components were chosen, accounting for approximately 65% of the population variance. Subsequently, a support-vector-machine-based algorithm was used with 10-fold cross-validation to discriminate ICM from NIDCM.

Results
Patients were 63±10 years (ICM: 63±10 years, NIDCM: 63±10 years, p=0.955), 74% male (ICM: 74%, NIDCM: 74%, p=1.000), and had a mean LVEF of 27±8% (ICM: 27±7%, NIDCM: 28±7%, p=0.688). Global time to peak strain was significantly shorter in ICM patients relative to NIDCM patients across all surfaces and in all directions (p<0.05). The highest single-variable Area Under the Curve (AUC) achieved for the classification of ICM versus NIDCM from global data was for minimum principal strain (ICM: 43.7±7.8, NIDCM: 48.3±7.5, p<0.001, AUC: 0.682) (Figure 1). However, a multi-feature machine-learning-based model exposed to all available regional 3D deformation data achieved an AUC of 0.903 (sensitivity 87.7%, specificity 75.5%).

Conclusions
Machine learning-based analyses of3D regionaldeformation patterns allows for robust discrimination of ICM versus NIDCM. Further expansion of the presented findings is planned on a wider, multi-centre cohort.

Acknowledgement/Funding
Dr. White was supported by an award from Heart and Stroke Foundation of Alberta. This study was funded in part by Calgary Health Trust.
4969Enhanced gap junction coupling organised and terminated acute ventricular fibrillation in ex-vivo perfused hearts
Authors: Handa B S , Li X , Roney C , Pitcher D , Chowdhury R A , Peter N S , Ng F S 
Published: October 2019

Abstract

Background
The underlying mechanism of ventricular fibrillation (VF) remains unclear. There are both experimental and clinical data to support the existence of rotational drivers (RDs), though other opposing studies suggest that VF is the result of disorganized myocardial activation. Abnormal electrical coupling between cardiomyocytes through gap junctions (GJ) has been considered an important factor in the genesis and maintenance of VF and pre-treatment with GJ couplers, rotigaptide (RTG), has been shown to reduce VF inducibility.

Purpose
We hypothesized that the degree of GJ coupling determines the underlying mechanism of VF, and that changes in GJ coupling can shift or modify the predominant mechanism of fibrillation along the spectrum between disorganised activity and organised drivers. We proposed that increased organisation of VF is critical to its termination.

Methods
Thirty Sprague-Dawley rat hearts were explanted, perfused ex-vivo and acute VF was induced with burst pacing and 30μM pinacidil. Optical mapping of transmembrane potential was performed at baseline and the effects of GJ coupling on VF dynamics were studied in an acute VF model by perfusing with increasing concentrations of a GJ uncoupler; carbenoxolone (0–50μM, CBX, n=10) or a GJ coupling-enhancer; RTG (0–80nM, n=10). A chronic diffuse fibrosis model (n=10) was generated with 4 weeks of in-vivo angiotensin infusion (500nm/kg/min). Fibrillation dynamics were quantified using phase analysis, phase singularity (PS) tracking and our novel method of global fibrillation organisation quantification, frequency dominance index (FDI), which is a power ratio of highest amplitude dominant frequency in the frequency spectrum.

Results
RTG increased average rotations per RD (Baseline: 2.86±0.10 vs 80nM: 5.66±0.43, p<0.001) whilst CBX caused a reduction (Baseline: 3.77±0.39 vs 50μM: 0.26±0.26, p<0.001). Maximum rotations for a RD increased with RTG (5.4±0.45 vs 48.20±12.32, p<0.001) and decreased with CBX (8.0±1.3 vs 0.3±0.3, p<0.001). Proportion of time PSs were detected in VF increased with RTG (0.44±0.06 vs 0.93±0.02, p<0.001) and decreased with CBX (0.61±0.9 vs 0.03±0.02, p<0.001). RTG reduced meander of longest duration RD (20.6±1.68 vs 11.51±0.77 pixels, p<0.001) for PS >5 rotations. FDI increased with RTG (0.53±0.04 vs 0.78±0.3, p<0.001) and decreased with CBX (0.60±0.05 vs 0.17±0.03, p<0.001). In the diffuse fibrosis group, in comparison to baseline RTG 80nM increased FDI (0.35 vs 0.65, p<0.001) and terminated VF in 40% of hearts.

Conclusion
The degree of GJ coupling is a key determinant of the underlying mechanism of VF. RTG organised fibrillation and stabilised RDs in a concentration-dependent manner whilst CBX disorganised VF. Enhancing GJ coupling with RTG in diseased hearts with fibrosis can terminate VF and may be a potential therapeutic target in acute VF.

Acknowledgement/Funding
BHF Programme Grant PG/16/17/32069
5034Is stroke an issue after transcatheter mitral valve repair? A systematic review and meta-analysis
Authors: Barros Da Silva P , Sousa J P , Oliveiros B , Donato H , Goncalves L , Teixeira R 
Published: October 2019

Abstract

Background
Transcatheter mitral valve repair (TMVR) is a minimally invasive therapeutic procedure used as an alternative to surgery for mitral valve regurgitation in high risk patients. This technique creates a double orifice area, which might be comparable to a mitral prosthesis or mitral stenosis. So far, no strict antithrombotic therapy has been recommended and different post-procedure protocols are being currently applied.

Objectives
To assess stroke rate after TMVR, comparing it with surgical mitral valve repair (SMVR) and optimal medical treatment (OMT).

Methods
We systematically searched PubMed, Embase and Cochrane databases, in December 2018, for both interventional or observational studies comparing TMVR with SMVR and/or OMT in the treatment of severe mitral regurgitation. Only studies including data on post-procedure stroke incidence were selected. Two authors independently screened articles for inclusion, risk of bias and data extraction. Random-effects meta-analysis for TMVR, SMVR and OMT were performed. Due to the low number of pooled events, a cumulative meta-analysis was subsequently implemented. The meta-analysis was registered on the Prospero database.

Results
15 studies were selected for qualitative analysis and, among these, 10 were included in the quantitative analyses (7 of TMVR vs. SMVR and 3 of TMVR vs. OMT), providing a total of 1881 patients. TMVR patients were older and had higher surgical risk scores than SMVR patients. Groups were homogeneous regarding previous atrial fibrillation rate (pooled OR 1.45 [0.82–2.55]), whereas post-procedure de novo atrial fibrillation was more frequent in SMVR when compared with TMVR (pooled OR 0.20 [0.06–0.7]). Although the pooled stroke rate was numerically lower in the TMVR group, there was no statistically difference in the stroke incidence between TMVR and SMVR (pooled OR 0.49 [0.17, 1.42], p=0.19, I2= 0%) – Panel A. On the other hand, cumulative meta-analysis was able to show a significantly lower stroke rate in TMVR, when compared to SMVR (OR 0.4 [0.40, 0.67], p<0.05). As for TMVR vs. OMT, no difference in stroke rate was identified (pooled OR 1.09 [0.60, 1.97], p=0.79, I2=0%) – Panel B.
Forest Plots – Stroke incidence

Conclusions
Post-procedure TMVR stroke rate was similar to that of patients managed with OMT only. For the same outcome, results favored TMVR when compared with SMVR, which might be related to its lower incidence of post-procedure de novo atrial fibrillation. These findings may prove insightful to future recommendations regarding the conundrum of the best antithrombotic strategy, particularly for patients with atrial fibrillation.
5036Increased 1-year mortality among patients discharged following hospitalization for pericarditis - a nationwide cohort study
Authors: Sigvardt F L , Hansen M L , Kristensen S L , Gustafsson F , Ghanizada M , Gislason G H , Madelair C 
Published: October 2019

Abstract

Background
Pericarditis accounts for 5% of all chest pain referrals to the emergency department and is generally considered a benign condition. However, recent studies suggested that pericarditis can be an early predictor of malignant disease, but data on mortality and other morbidity after incident pericarditis is lacking.

Purpose
To assess mortality risk and hospitalization patterns in patients with incident pericarditis.

Methods
In nationwide Danish registries we identified patients discharged from hospital with a first-time diagnosis of pericarditis from 1996 to 2016. Patients with prior myocarditis, heart failure, myocardial infarction and recent thoracic surgery were excluded.
The patients were risk set matched with 8 controls each from the general population on sex and year of birth. We assessed 1-year mortality risk using Kaplan Meier and logistic regression adjusted for baseline comorbidities; cerebrovascular disease, chronic obstructive lung disease, cardiac dysrhythmias, ischaemic heart disease and malignancy. We identified subsequent hospital admissions due to new onset cardiovascular-, respiratory- or malignant disease. Differences in frequencies between the pericarditis group and controls were calculated with Chi squared test.

Results
We identified 8,077 patients with pericarditis, median age 45 years (IQR: 32–59) and 75.6% were men. The absolute 1-year mortality was 2.9% in patients with pericarditis compared to 0.8% in the control group (p<0.001) (Figure 1).
The adjusted odds ratio (OR) of 1-year mortality was 2.79 (95%-CI: 2.14–3.65, p<0.001). Within the first year after incident pericarditis, hospital admission due to recurrent pericarditis was observed in 10.6% of the patients. Further, we observed significantly higher frequencies of other hospital admissions compared to the matched controls; cardiovascular disease: 4.6% vs, 1.2%, p>0.001, respiratory disease: 3.4% vs. 0.7%, p>0.001) and malignant disease: 1.4% vs. 0.5%, p>0.001).
Figure 1

Conclusion
In a nationwide cohort of patients discharged from hospital with incident pericarditis, we observed more than a triple 1-year mortality compared to age- and sex matched controls. Further, we observed a higher frequency of both cardiovascular and non-cardiovascular hospital admissions, highlighting the need for more focus on underlying morbidity in patients presenting with pericarditis.
5130Association between degree of LDL-cholesterol decrease after a myocardial infarction and mortality - a nationwide cohort study
Authors: Schubert J , Lindahl B , Melhus H , Renlund H , Leosdottir M , Allahyari A , Ueda P , Jernberg T , Hagstrom E 
Published: October 2019

Abstract

Background
In clinical trials, patients with myocardial infarction (MI) and elevated LDL-cholesterol (LDL-C) benefit the most from lipid lowering therapy, and more intensive LDL-C lowering therapy is associated with better prognosis.

Purpose
To investigate the association between degree of LDL-C lowering and prognosis in MI patients from a large real-world setting.

Methods
Patients admitted with an MI between 2006 and 2016 and registered in the Swedish MI-registry (SWEDEHEART) were followed until 2018. The difference in LDL-C between the MI hospitalization and a 6–10 week follow-up was measured. In multivariable Cox regression analysis adjusting for clinical risk factors (eg. age, diabetes, prior cardiovascular disease), the association between LDL-C change, mortality and recurrent MI was assessed using restricted cubic splines. Further, the patients were stratified according to quartile decrease in LDL-C from MI hospitalization to the follow-up.

Results
A total of 44,148 patients (median age: 64) had an LDL-C measured during the MI hospitalization and at follow-up. Of these, 9,905 (22.4%) had ongoing statin treatment prior to admission. The median LDL-C at the MI hospitalization was 2.96 (interquartile range 2.23, 3.74) mmol/L and the median decrease in LDL-C was 1.17 (0.37, 1.86) mmol/L. During a median follow-up of 3.9 years, 3,342 patients died and 3,210 had an MI. Patients with the highest quartile of LDL-C decrease (1.86 mmol/L) from index event to follow-up, had a lower risk of mortality, hazard ratio (HR) 0.59 (95% confidence interval [CI] 0.44–0.80) compared to those with the lowest quartile of LDL-C decrease (0.37 mmol/L) (figure). For MI, the corresponding HR was 0.83 (95% CI 0.68–1.02). Ongoing statin-use prior to admission did not alter the effect of LDL-C decrease and outcome in the analysis.

Conclusions
In this large nationwide cohort of MI patients, a gradually lower risk of death was observed in patients with larger decrease in LDL-C from index event to follow-up, regardless of statin use prior to admission. The same trend was observed for recurrent MI, although not reaching statistical significance. This confirms previous findings that efforts should be made to lower LDL-C after MI.