bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of novel biomarkers for predicting atrial fibrillation outcomes in patients with cardiovascular risk factors
Authors: Khashaba A , Brady P , Nehaj F , Schnabel RB , Kirchhof P , Fabritz L , Chua W 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): CATCH ME European Commission H2020 grant (no. 633196)

Background
Several novel blood biomarkers were recently found to reflect underlying pathophysiology implicated in atrial fibrillation (AF). These biomarkers could be used for stratifying patients at risk of developing AF or AF-related adverse events.

Purpose
We combined 9 clinical risk factors and 12 biomarkers to model composite outcomes of 1) incident AF, hospitalisation for arrhythmias, and cardiovascular death in sinus rhythm patients at risk of AF, and 2) recurrent AF, hospitalisation for arrhythmias, and cardiovascular death in patients with AF.

Methods
1455 patients presenting acutely to hospital with either diagnosed AF (n = 648) or sinus rhythm and ≥2 CHA2DS2-VASc risk factors (n = 807, silent AF ruled out by 7-day ECG monitoring) were followed up for two years. Outcomes were collected from linked hospital episode statistics (HES) and Office of National Statistics (ONS) data from NHS Digital. We univariately evaluated 12 cardiovascular biomarkers quantified from EDTA plasma collected at baseline (ANG2, BMP10, CA125, CRP, ESM1, FABP3, FGF23, GDF15, IGFBP7, IL6, NTproBNP, Troponin T). Two predictive models combining clinical characteristics and biomarkers were developed for each patient group, using Cox regression with backward elimination and considering non-cardiovascular death as a competing risk.

Results
In sinus rhythm patients (n = 117/807 with outcome), elevated BMP10, ANG2, CA125, IGFBP7, NTproBNP univariately predicted the composite outcome (adjusted for age, sex, body mass index (BMI), eGFR, heart failure, stroke/TIA, hypertension, diabetes, coronary artery disease – see Figure part A). In the combined model, age, prior stroke/TIA, coronary artery disease, ANG2, IGFBP7 and NTproBNP predicted the outcome (C-statistic [95% confidence interval (CI)] 0.733 [0.683, 0.784]).
In patients with AF (n = 193/648 with outcome), elevated BMP10, ANG2, CA125, troponin T, GDF15, IGFBP7, NTproBNP univariately predicted the composite outcome (adjusted for same variables as above – see Figure part B). In the combined model, high BMI, low eGFR, hypertension, IGFBP7, NTproBNP and troponin T were predictive of the composite outcome (C-statistic [95% CI]: 0.643 [0.596, 0.689]).

Conclusion
Combinations of clinical risk factors and biomarkers were predictive of two-year AF-related adverse events in sinus rhythm patients at risk of AF and in patients with AF. These markers could be used to identify patients for more intensive follow-up or therapy. IGFBP7 and NTproBNP were present in both models, implicating pathways involved with cardiac overload, inflammation, and oxidative stress. These findings call for external validation of these markers and prospective evaluation in at-risk populations. Abstract Figure. Biomarkers predicting 2-year AF outcomes
Application of recurrence plot analysis to characterise whole chamber propagation of atrial fibrillation
Authors: Pope M , Kuklik P , Briosa E Gala A , Leo M , Paisey J , Mahmoudi M , Betts TIMOTH 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Public hospital(s). Main funding source(s): Oxford Biomedical Research Centre

Introduction
Non-contact charge density mapping allows visualisation of whole chamber propagation during atrial fibrillation (AF). The identification of regions with repetitive or, conversely, more complex patterns of wavefront propagation may provide clues to mechanisms responsible for AF maintenance and lead to improved outcomes from catheter ablation. Our novel mapping approach based on signal recurrence plots has never been applied to whole chamber, bi-atrial recording of atrial fibrillation.

Purpose
To apply recurrence analysis to characterise whole chamber bi-atrial AF propagation.

Methods
Non-contact dipole signals from left and right atrial maps were obtained during simultaneous bi-atrial charge density mapping of AF. Signals were converted to phase and mean phase coherence calculated for the generation of recurrence distance matrices for the whole chamber and each anatomical region (6x LA and 4x RA) over the 30-second recording duration, where a value of 1 (purple, see figure panel A) represents uniform repetitive conduction, and 0 (red), irregular, non-repetitive activity. Whole chamber and regional mean recurrence values were calculated and correlated with the frequency of wavefronts of localised irregular activation patterns.

Results
Maps were obtained prior to ablation in 21 patients (5 paroxysmal (pAF), 16 persistent AF (persAF)) undergoing de-novo catheter ablation procedures. Whole chamber recurrence was higher in patients with pAF (0.40 ± 0.08) than persAF (0.34 ± 0.05), p &lt; 0.0005. There was an inverse correlation between regional recurrence values and the number of localised irregular activations detected (-0.7021, p &lt; 0.0005, figure panel B) with the lateral LA and anterior RA demonstrating the highest recurrence values in each chamber (figure panel C).

Conclusion
Use of recurrence distance matrices characterises global AF propagation phenotypes. Regional values are inversely correlated with the frequency of localised irregular activation patterns identified demonstrating an anatomic dependence in the level of AF propagation complexity, greatest in the anterior LA and septal RA. Comparison of strategies targeting regions with maximal vs. minimal values during catheter ablation may define an optimal approach to treatment of persistent AF. Abstract Figure. Recurrence abstract figure
Factors predicting adverse cardiovascular outcomes in patients with atrial fibrillation and heart failure with preserved ejection fraction
Authors: Saksena S , Slee APRIL , Lakkireddy D , Shah DIPEN , Di Biase LUIGI , Lewalter T , Natale A 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): Electrophysiology Research Foundation

Introduction
Atrial fibrillation (AF) is known to impact cardiovascular(CV) mortality in heart failure (HF) patients (pts) with preserved ejection fraction (pEF) but its exact causes are unknown.

Methods
We analyzed demographic, clinical, ECG and AF presentation as predictors of CV mortality, sudden death( SCD) and pump failure death(PFD) in HFpEF pts in the TOPCAT AMERICAS trial. We analyzed two AF presentations 1. Pts in sinus rhythm (SR, n = 1319) compared to AF on ECG (n = 446) at entry or 2. Pts with no AF event by history or ECG ( n = 1007 ) to those with any AF event (n = 760 ).
Results (Table): 5 year (yr) CV mortality was higher in pts with AF on ECG (30%) than SR (18%, p = 0.014) but 5 yr SCD was (10% in AF on ECG & 7% in any AF) & comparable to SR (7% & 9% respectively, p = ns). 5 yr PFD was higher in AF on ECG (13%) than SR (5%, p = 0.007)

Conclusions
: 1. CV death risk in HFpEF pts increased with AF on ECG.. 2. SCD was not more frequent with both AF presentations 3. PFD in HFpEF increased with age, ECG recorded AF & elevated heart rate. 4. The recording of AF on ECG was more strongly associated with CV death & PFD, possibly due to greater AF burden . Predictors of adverse outcomes in HFpEF AF on ECG* Any AF* Endpoint Covariate HR (95% CI) p-value HR (95% CI) p-value Time to cardiovascular death Atrial Fibrillation* 1.44 (1.08, 1.92) 0.014 1.15 (0.87, 1.51) 0.338 Age (years) 1.03 (1.02, 1.05) &lt;.001 1.03 (1.02, 1.05) &lt;.001 Black/AA (vs. White) 0.97 (0.65, 1.46) 0.002 0.96 (0.64, 1.44) 0.004 Other race (vs. White) 2.41 (1.46, 3.99) 2.32 (1.41, 3.83) Smoking 2.62 (1.63, 4.20) &lt;.001 2.60 (1.62, 4.17) &lt;.001 Diabetes 1.47 (1.12, 1.94) 0.006 1.45 (1.10, 1.91) 0.009 Systolic BP (mmHg) 0.99 (0.98, 1.00) 0.022 0.99 (0.98, 1.00) 0.014 Heart rate (bpm) 1.02 (1.00, 1.03) 0.012 1.02 (1.01, 1.03) 0.006 Time to Any sudden cardiac death Atrial Fibrillation* 1.17 (0.69, 1.96) 0.563 0.85 (0.53, 1.35) 0.484 Female (vs. Male) 0.46 (0.28, 0.75) 0.002 0.46 (0.28, 0.74) 0.002 Black/AA (vs. White) 1.57 (0.87, 2.82) 0.194 1.49 (0.83, 2.69) &lt;.001 Other race (vs. White) 1.76 (0.70, 4.41) 1.70 (0.68, 4.25) Diabetes 1.70 (1.07, 2.70) 0.024 1.65 (1.04, 2.62) 0.033 Time to pump failure death Atrial Fibrillation* 2.04 (1.22, 3.42) 0.007 1.62 (0.96, 2.75) 0.074 Age (years) 1.06 (1.03, 1.10) &lt;.001 1.06 (1.03, 1.10) &lt;.001 Heart rate (bpm) 1.03 (1.00, 1.05) 0.034 1.03 (1.01, 1.05) 0.015 Cox model of covariates associated with outcomes adjusted for baseline imbalances
The onset of paroxysmal non-valvular atrial fibrillation in men with hypertension is associated with an increase in blood levels of transforming growth factor beta 1
Authors: Koval S , Reznik LA , Starchenko TG , Mysnychenko OV , Penkova M YU 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.
Background. Patients with essential hypertension (H), primarily men, are characterized by early formation of left ventricular hypertrophy (LVH) followed by left atrial (LA) enlargement, which significantly increases the risk of development non-valvular atrial fibrillation (nAF). The most important pathogenic factor in the development of nAF is fibrosis of the LA myocardium. One of the key profibrogenic factors is transforming growth factor beta 1(TGF-beta1).
Purpose. To evaluate the blood levels of TGF-beta1 in hypertensive men with paroxysmal nAF and without AF.
Methods.The study included 57 men with H grade 2–3 and with LVH (age 48 ± 4 years), of those 26 with paroxysmal nAF and 31 without AF. Controls were 26 practically healthy men. All patients with paroxysmal nAF had an at least one episode of paroxysmal AF attack with spontaneous return to normal sinus rhythm and were in sinus rhythm at the time of the assessment. Patients with valvular heart disease, heart failure, ischemic heart disease, cardiomyopathy, cardiac surgery, thyroid disease, diabetes mellitus, obesity, anemia, infectious or pulmonary diseases were not included. The examination of patients include standard methods as well as echocardiography. Levels of TGF-beta1 in blood serum were measured by immune enzyme assay. All patients included in the study received standard antihypertensive therapy.
Results. It was found that the blood levels of TGF-beta1 in whole group of men with H were significantly higher (13,2 [5,3;22,5] ng/mL, р=0,034 ) than in practically healthy men (7,3 [2,3;16,5] ng/mL ). The highest blood levels of TGF-beta1 were found in hypertensive men with paroxysmal nAF (18,4 [9,2;31,8] ng/mL ) and significantly exceeded (р=0,018) those in hypertensive men without AF ( 11,6 [ 4,5;19,7] ng/mL ). The following positive correlations were found in whole group of men with H between TGF-beta1 blood levels and a number of echocardiographic parameters: LA size (LA volume/height2 ) (r = 0,510, р=0,012), LV mass index ( LV mass/BSA (g/m2) ( r = 0,411, р=0,027) and E/e′ (averaged) ratio (r = 0,357, р=0,036).
Conclusion. The data obtained indicate that TGF-beta1 can play an important role, both in the pathogenesis of pathological remodeling of the LV and LA in men with H, and in the development of AF in these patients.
Atrial fibrillation substrate mapping with decrement evoked potential mapping
Authors: Salvador-Montanes O , Fitzgerald J , Jackson N , Haldar S , Cotton J , Gizurarson S , Nanthakumar K , Porta-Sanchez A 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): Sociedad Española de Cardiologia.

OnBehalf
DEFINE-AF

Background
Identifying and targeting atrial substrate zones that are vulnerable to unidirectional block and slow conduction may be critical to improve the outcomes of atrial fibrillation (AF) ablation. Functional mapping of the atrial substrate with Decrement Evoked Potential (DeEP) and a single extrastimulus in this population could potentially lead to novel therapeutic strategies.

Aim
1) To systematically analyze whether the DEEP are present in the atrial tissue and their locations after pulmonary vein isolation. 2) To assess their relationship with the underlying voltage. 3) To assess the presence of DEEP as a function of the subtype of AF.

Methods
Consecutive patients with AF undergoing ablation were prospectively enrolled at 3 institutions. A biatrial voltage map was created and after pulmonary vein isolation (PVI). A drive train and an extrastimulus (atrial refractory period + 20ms) was delivered from an epicardial site (proximal CS) and an endocardial site (left atrial appendage (LAA). A multipolar mapping catheter was sequentially placed at 8 left atrial sites and 5 right atrial sites. Electrograms (EGMs) that showed a local delay of &gt;10ms in activation with the extrastimulus were identified as DEEPs. Patients were followed for a mean of 11 ± 5 months

Results
74 patients, 63 pers AF (85%), mean age 62 ± 8, mean LA size 41 ±12 mm were enrolled. Of 19240 EGMs analyzed, 8.2% showed DEEPs (54.6% with CS pacing and 45.4% with LAA pacing, p = 0.0001). The mean local decrement seen was 39 ms. Most DEEPs (76.2%) were identified in sites with a normal EGM at baseline with preserved voltages. DEEPs were differentially distributed within the regions mapped, more frequently in LA than RA (9.2% vs 6.6%, p &lt; 0.0001). Patients with persistent AF had a higher proportion of DEEPs than patients with paroxysmal AF (9.7% vs 5.1%, p &lt; 0.001).

Conclusions
Atrial DEEPs are: 1) More often identified when pacing endocardially. 2) More common in patients with persistent AF. 3) More frequent in the LA than in the RA. 4) Mostly located in regions with normal voltages at baseline. All those findings suggest the importance of the functional substrate mapping in the atrium and could lead to novel therapeutic targets. Abstract Figure. Example of atrial DEEP
Season of birth and cardiovascular mortality in atrial fibrillation: a population-based cohort study
Authors: Fauchier L , Bisson A , Bodin A , Spiesser P , Pierre B , Clementy N , Babuty D 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.
Background. Month and season of birth may be indicators for a variety of prenatal and early postnatal exposures and they have been associated with life expectancy in adulthood. It is suggested that people born in the autumn on the northern hemisphere live longer than those born during the spring or summer, who may have an increase in cardiovascular disease specific mortality. Only few studies have followed populations longitudinally and no study has investigated the relation between season of birth and mortality in patients with established cardiac conditions.
Methods. All patients with atrial fibrillation (AF) seen in an academic institution were identified in a database. We examined the clinical course of 8962 consecutive patients with AF seen over a 10-year period. The adverse outcomes were investigated during follow-up and we identified the causes of death. The relation between season of birth (autumn, winter, spring and summer) and mortality risk was assessed using Cox proportional hazard regression models using autumn as the reference. Analyses were also made separately for men and women.
Results. In these 8962 patients (age 70 ± 10 years, CHA2DS2VASc score 3.1 ± 1.7), 1253 deaths were recorded during a follow-up of 2.5 ± 3.0 years (median 1.2, interquartile 4.3 years, yearly rate of death 5.5%) and 97% of causes of death were identified. Cardiovascular deaths accounted for 54% and 43% for non-cardiovascular. The three main causes of death were heart failure (29%), infection (18%) and cancer (12%).
Season of birth was a significant predictor of cardiovascular mortality (overall p = 0.0006). The lowest mortality was seen for people born in autumn or winter and the highest mortality in those born in spring and summer. This was mainly related to a higher cardiovascular mortality in males (hazard ratio [HR] 1.46, 95%CI 1.10-1.93, p = 0.009 for males born in spring and HR 1.44, 95%CI 1.08-1.91, p = 0.01 for those born in summer when compared to males born in autumn as the reference) while this effect was not seen in women. In a model adjusted for age, CHA2DS2VASc score, HASBLED score, cardiovascular risk factors, other comorbidities, AF pattern, antithrombotic use and other cardiovascular drugs use, a higher cardiovascular mortality was still seen in males born in spring (adjusted HR 1.43, 95%CI 1.05-1.96, p = 0.03) or in summer (adjusted HR 1.46, 95%CI 1.07-1.99, p = 0.02) when compared to those born in autumn while this was not seen in women.
Conclusion. Birth in spring or summer is associated with a higher risk of cardiovascular mortality in male AF patients. Further studies should aim at clarifying the mechanisms behind this association, which would support the so-called fetal origins hypothesis.
Pregnancy-related complications and incidence of atrial fibrillation: a systematic review and meta-analysis
Authors: Al Bahhawi T , Aqeeli A , L Harrison S , A Lane D , Buchan I , Skjoth F , Sharp A , Lip GYH 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Pregnancy-related complications have been previously associated with incident cardiovascular disease. However, data are scarce on the association between pregnancy-related complications and incident atrial fibrillation (AF). This systematic review examines associations between pregnancy-related complications and incident AF.

Methods
A systematic search of the literature utilising MEDLINE and EMBASE (Ovid) was conducted from 1990 to 6 April 2020. Observational studies examining the association between pregnancy-related complications including hypertensive disorders of pregnancy (HDP), gestational diabetes, placental abruption, preterm birth, low birth weight, small-for-gestational-age and stillbirth, and incidence of AF were included. Screening and data extraction were conducted independently by two reviewers. Inverse-variance random-effects models were used to pool hazard ratios.

Results: Six observational studies met the inclusion criteria
one case-control study and five retrospective cohort studies, with four studies eligible for meta-analysis. Sample sizes ranged from 1,839-1,303,365. Mean/median follow-up for the cohort studies ranged from 7-36 years. Most studies reported an increased risk of incident AF associated with pregnancy-related complications. The pooled summary statistic from four studies reflected a greater risk of incident AF for HDP (hazard ratio (HR) 1.47, 95% confidence intervals (CI) 1.18-1.84; I2 = 84%) and from three studies for pre-eclampsia (HR 1.71, 95% CI 1.41-2.06; I2 = 64%; Figure).

Conclusions
The results of this review suggest that pregnancy-related complications particularly pre-eclampsia appear to be associated with higher risk of incident AF. The small number of included studies and the significant heterogeneity in the pooled results suggest further large-scale prospective studies are required to confirm the association between pregnancy-related complications and AF. Abstract Figure.
Subclinical thyroid dysfunction and incident atrial fibrillation - a systematic review and meta-analysis
Authors: Singh H , Shahid MZ , Harrison SL , Lane DA , Lip GYH , Logantha SJRJ 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Other. Main funding source(s): This project was supported by the MRes programme in the Institute of Life Course and Medical Sciences at The University of Liverpool.
Thyroid hormones can act directly and indirectly on the cardiovascular system and studies have demonstrated associations between overt and subclinical thyroid dysfunction and adverse cardiovascular outcomes including heart failure, myocardial infarction, and coronary heart disease. The aim of this study was to assess the association between subclinical thyroid dysfunction and atrial fibrillation (AF).
The protocol was registered on PROSPERO (CRD42020221565). MEDLINE and Scopus were searched from inception to 13th November 2020 for studies investigating subclinical thyroid dysfunction and incident AF. Risk of bias was assessed using the Risk of Bias Assessment Tool (RoBANS). The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Subgroup analysis was performed for post-operative and non-post-operative AF.
5413 records were identified. Nine cohort studies were suitable for inclusion in the systematic review, of which seven studies were included in the meta-analysis. The meta-analysis comprised 595,058 patients. Subclinical hyperthyroidism was associated with a 99% increase in the risk of incident AF (Risk ratio (RR): 1.99; 95% confidence intervals (CI); 1.43 to 2.77; p &lt; 0.0001; I² = 67%). Subclinical hypothyroidism was also associated with a greater risk of AF (RR: 1.24; 95% CI; 1.05 to 1.47; p = 0.01; I² = 65%). Subgroup analysis demonstrated a 76% increase in the risk of post-operative AF in patients with subclinical hypothyroidism compared to euthyroid post-operative patients (RR: 1.76; 95% CI; 1.36 to 2.28; p &lt; 0.0001; I² = 0%). Six studies were rated as low risk of bias and three as medium risk of bias according to the RoBANS tool. The quality of evidence for AF in subclinical hyper- and hypothyroid patients was low.
Subclinical hyperthyroidism and subclinical hypothyroidism were associated with a higher risk of incident AF and post-operative AF, respectively. The quality of the current evidence is low and ideally a randomised controlled trial should be conducted to confirm these associations and assess impacts of treatments. Abstract Figure.
Different implication in dementia between patients with atrial flutter and atrial fibrillation: a national cohort study
Authors: Chen YL 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.
Importance
Atrial fibrillation (AF) has been reported with increasing the risk of stroke and dementia. Atrial flutter (AFL) is also a risk of stroke with different discrepancies in clinical outcome. Little is known about the difference in the risk of dementia between AF and AFL.

Objective
To investigate if the risk of dementia is difference between AF and AFL.

Methods
The patients with newly diagnosed AF and AFL during 2001–2013 was retrieved from Taiwan’s National Health Insurance Research Database. Patients with missing information, aged &lt;20 years, history of valvular surgery, rheumatic heart disease, hyperthyroidism, and history of dementia were excluded. Propensity score matching (PSM) between AF and AFL was performed, which included patient comorbidities, past medical history, medications, and index date stratified by age. Primary outcome was defined as dementia at follow-up.

Results
A total of 232,425 AF and 7,569 AFL were eligible for analysis. After 4:1 PSM, we included 30,276 AF (aged 67.3 ± 15.7 years) and 100,065 AFL (aged 67.4 ± 16.0 years) for analysis. The risk of dementia was higher in AF patients compared with AFL patients (subdistribution HR (SHR)=1.52, 95% CI 1.39 - 1.66; p &lt;0.0001) before PSM and still higher in AF patients (SHR = 1.14, 95% CI 1.04 to 1.25; p = 0.0064). The risk was higher in AF patients without previous stroke after PSM and there was no difference between AF and AFL patients with previous stroke history.
Conclusions and relevance
Our finding supports that risk of dementia is higher in AF patients than AFL patients. However, the risk of dementia between patients with AF and AFL varies depending on whether there is a previous stroke history.