bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone morphogenetic protein 10 as predictor for adverse outcomes in patients with atrial fibrillation
Authors: Hennings E , Blum S , Aeschbacher S , Coslovsky M , Knecht S , Paladini R E , Krisai P , Kastner P , Ziegler A , Mueller C , Zuern C S , Bonati L , Conen D , Kuehne M , Osswald S 
Published: October 2022

Abstract

Background
Patients with atrial fibrillation (AF) face an increased risk of death and major adverse cardiovascular events (MACE). Bone morphogenetic protein 10 (BMP10) is a novel atrial-specific biomarker, but data about its prognostic value in AF patients are lacking.

Purpose
We aimed to assess the predictive value of BMP10 for death and MACE in AF patients in comparison to N-terminal prohormone of B-type natriuretic peptide (NT-proBNP).

Methods
Baseline concentrations of BMP10 and NT-proBNP were measured in stable patients with AF enrolled in Swiss-AF, a prospective multicenter observational cohort study. Primary outcomes were all-cause death and MACE (composite of heart failure hospitalization, cardiovascular death, stroke, systemic embolism, myocardial infarction). Measures of discriminative power were used to compare multivariable Cox proportional hazard models using the different biomarkers.

Results
A total of 2219 AF patients were included with a median follow-up of 4.3 years (IQR 3.9, 5.1). Mean age was 73±9 years and 27% were women. Incidence rate per 100 patient-years of all-cause death and MACE increased across BMP10 quartiles (Figure 1). In the multivariable adjusted Cox proportional hazard model, the hazard ratio (HR) and 95% confidence interval (CI) of BMP10 was 1.60 (1.37; 1.87) to predict all-cause death, and 1.54 (1.35; 1.76) to predict MACE. For all-cause death, the C-index (95% CI) was 0.783 (0.763; 0.809) for BMP10, 0.784 (0.765; 0.810) for NT-proBNP, and 0.789 (0.771; 0.815) for both biomarkers combined. For MACE, the C-index (95% CI) was 0.732 (0.715; 0.754) for BMP10, 0.747 (0.731; 0.768) for NT-proBNP, and 0.750 (0.734; 0.771) for both biomarkers combined. When grouping patients according to clinical used NT-proBNP categories (&lt;300, 300–900, &gt;900 ng/l), higher incidence rates and adjusted HRs were observed for the primary outcomes in patients with high BMP10 in the categories of low NT-proBNP (all-cause death aHR 2.28 [1.15; 4.52], MACE aHR 1.88 [1.07; 3.28]) and high NT-proBNP (all-cause death aHR 1.61 [1.14; 2.26], MACE aHR 1.38 [1.07; 1.80]) (Figure 2).

Conclusion
The novel atrial-specific biomarker BMP10 strongly predicts all-cause death and MACE in patients with AF. BMP10 provides additional prognostic information in low- and high-risk patients according to NT-proBNP stratification.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Swiss National Science Foundation, Swiss Heart Foundation
Prognosis of atrial fibrillation with or without comorbidities. Analysis of younger adults from a nationwide database
Authors: Cottin Y , Mertz V , Bentounes S A , Pastier Debeaumarche J , Didier R , Herbert J , Zeller M , Lip G Y H , Fauchier L 
Published: October 2022

Abstract

Background
“Lone AF” may be defined as AF in younger adults (age &lt;60 years) and lack of obvious associated CV or extra CV conditions. However, current ESC guidelines indicate that the term of “Lone AF” is potentially confusing and should be abandoned because a cause may be present in every patient. In addition, studies on prognosis of “Lone AF” are inconsistent, likely as the result of the heterogeneity in definitions, comorbidities, study population and duration of follow-up. We aimed to assess the prognosis of patients with AF with or without cardiac or extra cardiac concomitant conditions.

Participants and methods
From the French administrative hospital-discharge PMSI database (Programme de Médicalisation des Systèmes d'Information) covering hospital care and representative of the whole French population, all consecutive patients with AF diagnosis hospitalized between 2011 and 2020 were identified. Patients were classified into four groups: 1) &gt;60 yo; 2) with known cardiac disease (KCD group); 3) with extra cardiac comorbidities (ECC); and 4) AF without KCD or ECC (“Lone AF”).

Results
Altogether 2,435,541 patients were identified, from which 2203,702 patients aged &gt;60 years and 231,839 patients aged &lt;60 years [with KCD (55.2%), with ECC (14.7%) and with “Lone AF” (30.1%)]. During follow-up the incidences of all-cause and CV deaths were 13.7%, 5.7%, 6.2% and 2.3%, and 4.2%, 1.7%, 0.8% and 0.3% in the older than 60 yo group, KCD group, ECC group and “Lone AF” AF group, respectively. In the age and sex-adjusted analysis (patients &lt;60 yo), patients with AF and KCD had worse outcomes than patients with “Lone AF” for all major cardiac events (see figures).

Conclusion
There are three distinct prognostic criteria based on the presence or not of HD or extra cardiac concomitant comorbidities. Patients in the so-called “Lone AF” group remain severe in terms of CV events but still with a lower incidence than the patient with associated KCD or ECC. The presences of KCD or ECC make it possible to distinguish a profile in terms of events that are very different from the patients.

Funding Acknowledgement
Type of funding sources: None.
Characteristics of incident atrial fibrillation patients – a nationwide register-based study with information from primary-, secondary- and tertiary care
Authors: Kouki E , Salmela B , Haukka J , Halminen O , Karlsson E , Mustonen P , Putaala J , Linna M , Aro A , Hartikainen J , Airaksinen K E J , Lehto M 
Published: October 2022

Abstract

Introduction
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with a current prevalence of 4.1% in Finland. Many of the comorbidities associated with AF are known risk factors for the arrhythmia and vice versa, as well as contributors to the risk of stroke and other AF related adverse events. A generally used evaluation method for the risk of stroke is the clinical risk factor -based CHA2DS2-VASc score, but other thromboembolic risk factors also exist.

Purpose
To better understand current AF population, this study describes characteristics, comorbidities, medication, and laboratory values of Finnish AF patients at the time of first AF diagnosis.

Methods
The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study is a nationwide register-based cohort study in which AF patient data has been linked from several Finnish health care- and national registers, with information from primary-, secondary-, and tertiary care. This substudy consists of patients over 20 years old with available laboratory data and an incident AF diagnosis (ICD-10 I48) between 1/1/2010–31/12/2018 in any of the used registers.

Results
Within the study period 143,455 patients with a new AF were registered. The mean age at time of diagnosis was 69.1 years for men and 76.3 years for women. The mean CHA2DS2-VASc score when entering the cohort was 3.48 (SD 1.88), and 84.9% of the cohort had at least one of the comorbidities included in the CHA2DS2-VASc score. The most prevalent comorbidities and medications of the cohort are shown in the figure, and a more comprehensive look is presented in the table. The medications listed have been in use during the year before cohort entry.

Conclusion
Atrial fibrillation does not come alone. Almost all patients diagnosed with AF have previous comorbidities and medications. Future analysis will provide information on how these evolve after AF diagnosis and elucidate their association with different endpoints.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital District
Paradoxical association between lipid levels and incident atrial fibrillation according to statin usage
Authors: Ahn H J , Lee S R , Choi E K , Lee S W , Han K D , Kwon S , Oh S , Gregory L I P 
Published: October 2022

Abstract

Background
In epidemiology studies, a higher level of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) is associated with a lower risk of atrial fibrillation (AF). Statin use might exert possible confounding effects in the paradoxical relationship; however, the inverse link between AF and cholesterol level that distinguishes statin users from non-users has not been evaluated.

Objective
We investigated the epidemiological relationships of TC–AF and LDL-C–AF in statin users and non-users, respectively.

Methods
From the Korean National Health Insurance Service database, we included 9,778,014 adults who underwent a health examination in 2009 and had no prior AF history. The levels of TC and LCL-C at the health exam were categorized in quartile (Q) and decile (D) values of the total study population. The study population was grouped into statin users and non-users, and TC–AF and LDL-C–AF relationships were evaluated.

Results
867,336 (8.9%) were on statin use among the total population. Statin users showed higher TC level (208.4±55.6 vs. 194.1±39.5 mg/dL, p&lt;0.001) and LDL-C level (123.0±102.2 vs. 121.3±226.3, p&lt;0.001) compared to non-users. Inverse associations of TC–AF and LCL-C–AF were observed; higher levels of TC and LDL-C were associated with a lower risk of AF. The hazard ratios (HR) and 95% confidence intervals (CI) were 0.797 (0.786–0.809) for the highest quartile of TC (Q4, TC ≥218) and 0.832 (0.82–0.843) for the highest quartile of LDL-C (Q4, LDL-C ≥135) when adjusted by age, sex, lifestyle behaviors, comorbidities, and low-income status. Statin users exhibited higher AF incidence rate than non-statin users, but the association in statin users generally tracked that seen among non-statin users demonstrating similar HR in Q4 of TC [0.812 (0.790–0.835) for statin users and 0.812 (0.798–0.826) for non-statin users] and LDL-C [0.842 (0.819–0.865) for statin users and 0.849 (0.835–0.863) for non-statin users].

Conclusion
The paradoxical relationship between lipid levels (TC and LDL-C) and incident AF remained consistent both in statin users and non-users. Further research is required to investigate an underlying mechanism for the cholesterol paradox of AF which still seems evident despite the pleiotropic effects of statin.

Funding Acknowledgement
Type of funding sources: None.
Prevalence of atrial fibrillation and feasibility of pulmonary vein isolation after patent foramen ovale closure
Authors: Fabbricatore D , Paolisso P P , Gallinoro E G , De Colle C D C , Valeriano C V , De Schouwer K D S , Geelen P G , Barbato E B , De Potter T D P 
Published: October 2022

Abstract

Background
Data about prevalence and the risk of atrial fibrillation, stroke, and need for pulmonary vein isolation (PVI) after device closure of a patent foramen ovale (PFO) are still lacking.
We aim to investigate the prevalence and the risk of atrial fibrillation after PFO closure and the feasibility of PVI in a PFO closure cohort compared to contemporary PVI without PFO closure.

Methods
Retrospective observational study of consecutive patients undergoing PFO closure enrolled from February 2013 to September 2020. Patients were divided into 3 groups: i) patients without AF before and after the procedure (n=132), ii) patients with paroxysmal AF prior to the procedure (n=21), iii) patients with documented AF after the procedure (n=13). All patients with AF occurrence were treated with adequate anticoagulation therapy according to the current ESC Guidelines. We compared the procedural data of these patients to a matched contemporary cohort without previous PFO closure undergoing PVI in our center. AF and stroke prevalence and PVI feasibility after PFO closure were assessed at follow up.

Results
One-hundred and sixty-six consecutive PFO closure patients were enrolled; the mean age was 54±13 years. Median follow-up was 3.5±2.5 years. During the study period, 21 patients had AF before or after the PFO closure (group 2) and 13 (7.8%) new onset AF (group 3). Stroke after the PFO closure occurred in 8 patients (4.8%), of which 4 in the group with new onset AF (30% of the group 3).
Among the 34 patients with AF, 10 patients (6%) underwent a PVI. Compared to a contemporary matched PVI cohort, total procedural times and fluoroscopy times were significantly higher in the patients with previous PFO closure (108±15 vs 75±29, p=0.002 and 3±1.5 vs 8±7, p&lt;0.001). Similar rate of AF relapses (p=0.198) was observed between the two groups, with a trend for higher rate of complication (pericardial effusion) for the cohort with previous PFO closure (p=0.06).

Conclusion
This study shows that a more accurate screening and treatment of AF is needed in patients with cryptogenic stroke despite the presence of a PFO, possibly a bystander. In our study, 30% of patients with new onset AF after PFO closure, experienced a further stroke after the procedure. In case of AF, the indication for PVI should be considered prior to the PFO closure since it turns out to be more difficult in terms of procedural and fluoroscopy times and risks of complications after PFO closure.

Funding Acknowledgement
Type of funding sources: Public Institution(s).
Searching for underlying atrial fibrillation using artificial intelligence-assisted MRI images from ischemic stroke patients
Authors: Zhang Z , Lin K , Wang J , Ding L , Sun Y , Fu C , Qian D , Li J , Huang D 
Published: October 2022

Abstract

Background
Nearly 30% of ischemic strokes are attributed to atrial fibrillation (AF) related cardiac thromboembolism. This subset of strokes are associated with higher recurrence rate, morbidity and mortality. As a result, current recommendation suggests a cardiac monitoring of variable intensity and duration to search for unknown AF after a stroke so that optimal secondary prevention could be administered. Unfortunately, it is reported that 24h Holter ECG monitoring for underlying AF is completed routinely in only a minority of stroke centers, making a huge gap between AF detection rate in clinical practice and estimated actual data (2–3% vs 23–30%). So, it is obvious that paroxysmal AF remains undetected in a significant proportion of patients after a stroke and an early and effective identification approach of cardiac disturbances is needed.

Purpose
We aim to develop an innovative end-to-end artificial intelligence model to rapidly search for atrial fibrillation in post ischemic stroke patients using MRI imaging data.

Methods
489 patients diagnosed with ischemic stroke, 174 of which had a prior known history of AF or new AF detected by intensive ECG monitoring poststroke, from January 2018 to October 2021 were enrolled in this study. The MRI images obtained after their admission in the stroke unit were meticulously evaluated and acute ischemic stroke lesions on DWI sequences were segmented and confirmed by two senior neuroradiologists independently. These processed images were randomly split into training (n=315) and testing set (n=174) for the implementation and validation of our AI screening model. And the algorithm was based on the combination of radiomic features and semantic features extracted from convolutional neural network (CNN). The model performance was evaluated by accuracy, recall, precision, F-Measure and AUC. Also, heatmaps which indicate the attention mechanism of the model were generated for interpreting underlying patterns.

Results
The AUC of our model (COM) reached 0.8 (Figure 1A). Also, the algorithm yielded values for the accuracy, recall, precision and F-Measure of 70%, 92.5%, 63.8% and 75.5%, respectively, which showed satisfactory classification results. As to the interpretability of the AI model, we found that more “attention” was paid to the main lesions (Figure 1B) and radiomic features which indicated the minimum gray level intensity and the sphericity of the lesions (Figure 1C, D) were crucial to the classifier.

Conclusions
Our work revealed a potential correlation between brain ischemic lesion pattern on DWI images and underlying etiology of AF. Moreover, the AI model we developed may serve as a rapid screening tool for AF in clinical practice of stroke units.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China
Impact of metabolic syndrome on the risk of ischemic stroke in non-anticoagulated atrial fibrillation patients having low CHA2DS2-VASc scores
Authors: Ahn H J , Choi E K , Lee S R , Lee S W , Han K D , Kwon S , Oh S , Gregory L I P 
Published: October 2022

Abstract

Background
Metabolic syndrome (MetS) predisposes to a thromboembolic state. However, conflicting results have been reported on whether MetS confers an increased risk of ischemic stroke in atrial fibrillation (AF), especially in patients with low CHA2DS2-VASc score who are not indicated for oral anticoagulant therapy.

Purpose
We investigated the risk of ischemic stroke according to the presence of MetS, the number of MetS components (metabolic burden), and the individual metabolic components in non-anticoagulated AF patients with low CHA2DS2-VASc score.

Methods
A total of 76,015 oral anticoagulant-naïve AF patients with low CHA2DS2-VASc score (0,1 in male and 1 in female) were included from the Korean National Health Insurance Service database. The status of MetS and individual metabolic components were evaluated based on health examination data within two years of AF diagnosis. We estimated the risk of ischemic stroke according to MetS, metabolic burden, and an individual component of MetS using Cox proportional-hazards models.

Results
The mean age was 49.8±11.1 years and 52,388 (68.9%) were male. The average CHA2DS2-VASc score was 0.7±0.5 and MetS was prevalent among 21,570 (28.4%) of the study population. During a mean follow-up of 5.1 years, ischemic stroke was developed in 1,395 (1.84%) patients. MetS was associated with a higher risk of ischemic stroke after adjustment for age, sex, lifestyle behaviors, low income, and cardiovascular comorbidities: adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) 1.06–1.33, p=0.002. A positive linear correlation was observed between metabolic burden and ischemic stroke risk. Patients with five MetS components showed the highest aHR of 1.55 (95% CI 1.14–2.11, Figure 1 and Figure 2), whereas those with a single MetS component had a marginal risk of ischemic stroke (aHR 1.18, 95% CI 0.99–1.41). Among individual metabolic components, elevated blood pressure and increased waist circumference was significantly associated with an increased risk of ischemic stroke: aHR (95% CI), 1.45 (1.30–1.62), p&lt;0.001, and 1.15 (1.03–1.30), p=0.016, respectively.

Conclusions
Among AF patients initially with CHA2DS2-VASc score 0 and 1 with no anticoagulation, the presence of MetS is associated with an increased risk of ischemic stroke. Given the linear incremental correlation between metabolic burden and ischemic stroke, special attention to the care of metabolic derangements is required in AF patients who are not indicated for anticoagulation.

Funding Acknowledgement
Type of funding sources: None.
Association between early rhythm control and the risk of dementia in patients with atrial fibrillation and prior history of stroke: a nationwide population-based study
Authors: Lee S R , Choi E K , Lee S W , Han K D , Oh S , Lip G Y H 
Published: October 2022

Abstract

Background
Patients with atrial fibrillation (AF) who experienced stroke before are at high risk for dementia. Although early rhythm control in patients with AF reduces the risk of stroke, there is a lack of evidence on whether early rhythm control reduces the risk of developing dementia in patients with new-onset AF and a history of prior stroke.

Purpose
To compare the risk of dementia between early rhythm control therapy and usual care in patients with new-onset AF and a history of prior stroke

Methods
Using the Korean nationwide claims database, we identified patients who were newly diagnosed as AF and had a history of prior stroke. Patients with prevalent dementia were excluded. Patients who received rhythm control therapy, including antiarrhythmic drug, direct current cardioversion, or AF catheter ablation, within 1 year after incident AF were defined as the early rhythm control group, otherwise as the usual care group. The inverse probability of treatment weighting method was used to balance baseline characteristics between the two groups. The incidence of all dementia, Alzheimer dementia, and vascular dementia were evaluated during follow-up.

Results
A total of 41,370 patients were included (mean age, 70±11 years; mean CHA2DS2-VASc score 5.3±1.6; 43% female); 10,213 were in the early rhythm control group and 31,157 in the usual care group. All patients received oral anticoagulants. During a median 2.7 years of follow-up, 6414 patients developed incident dementia (incidence rate, 4.9 per 100 person-years). Compared to usual care, early rhythm control was associated with lower risks of all dementia, Alzheimer dementia, and vascular dementia (weighted hazard ratio [95% confidence interval], 0.825 [0.776–0.876], 0.831 [0.774–0.893], and 0.800 [0.702–0.913], respectively, all p&lt;0.001) (Figure 1). The beneficial effect of early rhythm control on the risk of dementia were consistent regardless of the characteristics of prior stroke, for example, recent stroke within 6-month from their enrollment, disabling stroke that required continuous rehabilitation therapy, and severe stroke causing intensive care unit admission.

Conclusion
Early rhythm control within 1 year after AF diagnosis might be beneficial to prevent dementia in patients with incident AF and a history of stroke. To prevent progression of further cognitive dysfunction, early rhythm control should be considered in these patients.

Funding Acknowledgement
Type of funding sources: None.
Prediction of atrial fibrillation in patients with embolic stroke with undetermined source using electrocardiogram deep learning algorithm and clinical risk factors
Authors: Lee J H , Kwon J , Lee M S , Cho Y , Oh I Y , Park J , Jeon K H 
Published: October 2022

Abstract

Background
Combining the artificial intelligence algorithm with the known clinical risk factors may provide enhanced accuracy for prediction of the hidden atrial fibrillation (AF) in patients with embolic stroke with undetermined source (ESUS).

Purpose
We aimed to develop enhanced prediction models for AF with deep learning algorithm (DLA) and clinical predictors in patients with ESUS. The DLA was created to identify the patients with paroxysmal AF based on their electrocardiograms (ECG) during sinus rhythm.

Methods
We analyzed the 221 patients who underwent insertable cardiac monitor (ICM) for AF detection following ESUS. The DLA was previously developed with sinus rhythm ECGs of 10,605 paroxysmal AF patients and 50,522 non-AF patients. The convolutional neural network was used for the DLA. The primary endpoint was defined as any AF episode lasting over 5 min by ICM. The atrial ectopic burden (AEB) was calculated as the percentage of the number of conducted QRS by atrial ectopy on Holter monitoring.

Results
AF (≥5 min) was detected by ICM in 32 patients (14.5%) during follow-up period of 15.1±8.6 months. AF patients had higher AEB (0.199% vs 0.023%, p&lt;0.001), larger left atrial diameters (LAD, 41.2 mm vs 35.7 mm, p&lt;0.001), and larger left atrial volume index (LAVI, 46.4 ml/m2 vs 32.3 ml/m2, p&lt;0.001) than those without AF. The means of calculated probabilities of AF by DLA were higher in patients with AF than those without AF (63.8% vs 40.2%, p&lt;0.001). In the receiver operating characteristic curve analysis, the areas under the curve (AUC) were the highest in DLA (0.824) followed by AEB (0.784), LAVI (0.780), and LAD (0.768). The multivariable model with AEB, LAVI, and DLA demonstrated excellent prediction accuracy for paroxysmal AF (AUC: 0.902, Figure 1)

Conclusions
In patients with ESUS, the DLA outperformed other clinical risk factors for prediction of AF. Combining DLA with AEB, LAD and LAVI could is a potential useful tool to predict AF in ESUS patients.

Funding Acknowledgement
Type of funding sources: None.