bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct oral anticoagulation versus warfarin in atrial fibrillation: a nationwide cohort study of effectiveness and safety among frail patients
Authors: Nielsen P B , Ording A G , Skjoeth F , Larsen T B , Soegaard M 
Published: November 2023

Abstract

Background
Frail patients with atrial fibrillation carry a high risk of both stroke and treatment-related bleeding complications, but evidence for the safety and effectiveness of anticoagulation regimens in frail patients remain sparse.

Objectives
To determine the comparative effectiveness and safety of DOAC versus warfarin in frail patients with atrial fibrillation.

Methods
A nationwide registry-based cohort study applying a new-user design including all frail patients with atrial fibrillation who redeemed a prescription for DOAC or warfarin between January 2012 and December 2020. We applied inverse probability of treatment weighting (IPTW) to account for baseline confounding and applied a marginal structural modelling approach with weighted pooled regression to compute hazard ratios (HR) and risk differences for thromboembolic events and major bleeding comparing specific DOAC doses with warfarin.

Results
We identified 32048 anticoagulation naïve frail patients (median age 80 years, 53% female) with atrial fibrillation who started anticoagulation treatment: 6747 (21.1%) patients initiated warfarin therapy, 17076 (50.3%) initiated standard dose DOAC, and 9179 (28.6%) patients with indication for dose reduction initiated reduced dose DOAC. The median CHA2DS2-VASc score was 5. The comparative effectiveness analyses showed a similar risk for thromboembolism with weighted HRs of 0.95 (95% CI 0.80-1.13) for standard dose DOAC versus warfarin, and 0.97 (95% CI 0.77-1.23) for reduced dose DOAC versus warfarin (see Table). The thromboembolic event free survival difference at one year was -0.2% for DOAC regardless of dosing when compared with warfarin. The comparative safety analyses revealed significantly lower risk of major bleeding among patients initiating standard dose (weighted HR 0.69, 95% CI 0.59-0.87) or reduced dose DOAC (weighted HR 0.67, 95% 0.55-0.81) when compared with warfarin. The risk difference of bleeding at one year for DOAC users varied between -1.3% and -3.0%, with the greatest difference for patients with high frailty level initiating reduced dose DOAC.

Conclusion
We observed similar risk of thromboembolism and significantly lower risk of major bleeding associated with both standard and reduced DOAC treatment regimens compared with warfarin in frail patients with atrial fibrillation in routine clinical practice.
10-year trends in oral anticoagulation therapies and ischemic stroke among 157,583 patients with non-valvular atrial fibrillation
Authors: Sun W , Tam T K , Yan B 
Published: November 2023

Abstract

Purpose
Initiation of oral anticoagulation therapy (OAC) for stroke prevention in patients with atrial fibrillation (AF) is often suboptimal in clinical practice. We aimed to describe trends in OAC uptake and incidence of ischemic stroke over the past decade.

Methods
We retrospectively analyzed consecutive patients with non-valvular (NV) AF between January 2012 and July 2022 from 16 public hospitals. Annual incidence of AF was the number of new AF cases as proportion of adult population reported by Census and Statistics Department. Prescription of OAC (vitamin K antagonist (VKA) and direct oral anticoagulants (DOAC)) were recorded. OAC uptake was defined as initiation of OAC within 12 months from AF diagnosis. Incidence of ischemic stroke was calculated for both incident and prevalent AF cohorts over time. Logistic regression was conducted to identify predictors of OAC uptake.

Results
157,583 NVAF patients (mean age 76.6±12.5 and female 49.6%) with mean CHA2DS2VASC 2.6±1.3 were identified. Between 2012 and 2022, incidence of new AF was steady across the years with mean of 0.19%±0.03% (range 0.16% to 0.24%) per year. OAC prescription increased from 15.3% to 46.0% and the incidence of ischemic stroke decreased significantly from 4.0% to 0.6% over the last decade (both p for trend &lt;0.01). DOAC use increased steadily from 6.2% to 41.0% whereas VKA decreased from 9.1% to 3.5% (Figure). Mean time from AF diagnosis to OAC prescription was 0.6±1.6 months. Of all patients prescribed OAC, 40.8% initiated OAC within 1 month after AF diagnosis. CHA2DS2VASC scores ≥4 was associated with higher likelihood of OAC uptake (OR=1.74 (95%CI: 1.69-1.78).

Conclusion
Our real-world data demonstrated steady incidence of new NVAF diagnosis with increasing trend in OAC prescription, predominantly DOAC and decreasing incidence ischemic stroke over the last decade. However, overall utilization of OAC for stroke prevention remains suboptimal.
Comparison of clinical and genetic risk model based on ethnicity for ischemic stroke after atrial fibrillation catheter ablation
Authors: Park J W , Kim D H , Yu H T , Kim T H , Uhm J S , Joung B Y , Lee M H , Pak H N 
Published: November 2023

Abstract

Introduction
CHA₂DS₂-VASc score (CVS) is widely used to estimate the risk of stroke in atrial fibrillation (AF) patients. However, CVS does not include genetic risk, and the risk model for stroke dose not well developed after AF catheter ablation (AFCA). We explored the clinical and genetic risks for ischemic stroke (IS) and compared the difference in prediction power according to ethnicity.

Methods
We used available genome-wide association study (GWAS) data in European (34217 IS, 406111 controls) and Asian (22664 IS, 152022 controls) to develop polygenic risk score (PRS) for IS in 2897 independent Korean AF patients (Median 60 [IQR 52, 67] years, male 74.0%, paroxysmal AF 66.3%, anticoagulation rate 60% in 1367 patients over 2 points of CVS) who underwent the AFCA. The patients with IS within 2 weeks after the AFCA were excluded. In the independent AF cohort during the median 50 [IQR 28-94] months follow-up, 48 experienced the IS after the AFCA. We developed two different PRS derived from European and Asian GWAS data and then two different CVS-combined PRS models in the independent cohort. After including SNPs with p-value &lt;5e-8 in the development cohort, rs635634 and rs671 were used in the CVS-combined European PRS (CVS-EPRS) and CVS-combined Asian PRS (CVS-APRS) model, respectively in the independent cohort. We compared the C index of risk models to investigate the prediction power for the IS.

Results
The CVS was significantly higher in the patients with IS than in their counterparts (3.0 IQR [1.0, 4.0 vs. 1.0 [1.0, 2.0], p&lt;0.001). The overall C index was 0.716 in CVS alone model, 0.711 in the CVS-EPRS model, and 0.725 CVS-APRS model. For predicting 1-year IS after the AFCA, the CVS-APRS model improved the C index as compared to CVS alone model (0.834 vs. 0.813, p=0.037). For predicting 3-year IS after the AFCA, the C-index was higher in the CVS-APRS model as compared to the CVS-EPRS model (0.746 vs. 0.721, p=0.030)

Conclusions
In AF patients with the AFCA, genetic polymorphism with clinical risk factors contributed to predict the 1-year IS. However, ethnicity might be an important factor in adapting genetic contributions to predicting IS.Study flow chartTime dependent ROC curve
Arterial thromboembolism in patients with atrial fibrillation and CHA2DS2-VASc score 1: a nationwide study
Authors: Ostergaard L , Olesen J B O , Petersen J K P , Nielsen L S N , Kristensen S L K , Schou M S , Kober L K , Fosbol E L F 
Published: November 2023

Abstract

Background
Knowledge is sparse on whether rate of stroke differs in patients with atrial fibrillation (AF) and a CHA2DS2-VASc of 1 according to how this point is obtained.

Objectives
To examine the associated rate of thromboembolism according to subgroups with a CHA2DS2-VASc of 1.

Methods
From nationwide registries, patients with incident AF from 2000–2021 and without oral anticoagulants were categorized according to the CHA2DS2-VASc score (CHA2DS2-VASc 0, CHA2DS2-VASc 1: heart failure [HF], hypertension [HT], diabetes mellitus [DM], vascular disease, age 65-74, or CHA2DS2-VASc 2, due to age ≥75 years). Female sex was not considered a risk factor. Outcome was one-year rate of thromboembolism (ischemic stroke, embolism of extremity, or transient cerebral ischemia). Main safety outcome was hospitalization with bleeding. The cumulative incidence of thromboembolism and bleeding were computed for CHA2DS2-VASc 0, the five subgroups of CHA2DS2-VASc 1, and CHA2DS2-VASc 2 (due to age ≥75 years) accounting for death as competing risk. For comparison between study groups crude Cox proportional hazard analysis was used.

Results
We included 29,369 patients with CHA2DS2-VASc 0; 27,845 patients with CHA2DS2-VASc 1: 1,890 (6.8%) patients with HF, 9,649 (34.7%) with HT, 968 (3.5%) with DM, 906 (3.3%) with vascular disease, 14,432 (51.8%) with age 65-74 years; 19,387 patients with CHA2DS2-VASc 2 (age ≥75 years). At one year of follow-up, the cumulative incidence of thromboembolism was 1.1% for CHA2DS2-VASc 1, 2.7% for CHA2DS2-VASc 1 (overall), and 4.9% for CHA2DS2-VASc 2 (age ≥75 years). Within subgroups of CHA2DS2-VASc 1, the cumulative incidence of thromboembolism was 1.7% for HF, 2.6% for HT, 2.2% for DM, 2.7% for vascular disease, and 2.9% for age 65-74 years (Figure 1). Within subgroups of CHA2DS2-VASc 1, age (65-74 years) was associated with the highest rate of thromboembolism, while HF was associated with the lowest rate (Figure 2). The one-year cumulative incidence of hospital admission with bleeding was 0.4%, 1.2%, 1.1%, 1.4%, 1.8%, 1.2%, and 2.2% for CHA2DS2 -VASc 0, CHA2DS2-VASc 1: HF, HT, DM, vascular disease, age 65-74, and CHA2DS2 -VASc 2 (age ≥75), respectively.

Conclusion
Within the spectrum of CHA2DS2-VASc 1, age seemed to be the risk factor with most impact on the rate of thromboembolism, while HF seemed to have the least impact. All subgroups of CHA2DS2-VASc 1 were associated with lower rate of arterial thromboembolism as compared with CHA2DS2-VASc 2 and a higher rate as compared with CHA2DS2-VASc 0.
These findings lay the ground for a better understanding of when to initiate oral anticoagulation in patients with CHA2DS2-VASc 1.
The gender difference in risk factor and incidence rate of hospitalization for heart failure in Japanese atrial fibrillation patients: The Fushimi AF Registry
Authors: Doi K , Nakanishi Y , Minami K , Ishigami K , Ikeda S , Hamatani Y , Yoshizawa T , Ide Y , Fujino A , Ishii M , Iguchi M , Masunaga N , Abe M , Akao M 
Published: November 2023

Abstract

Background
Gender-specific medicine is of concern in cardiovascular medicine. However, the gender difference in risk factor and incidence rate of hospitalization for heart failure (HF) in Japanese atrial fibrillation (AF) patients is little known. The aim of this study is to compare the risk factor and incidence rate of HF hospitalization in male and female.

Method
In the Fushimi AF Registry, we started to enroll patients from March 2011, and follow-up data were available for 4,496 patients by the end of February 2022. In the entire cohort, 2,677 were male and 1,819 were female. We compared clinical characteristics and risk factor and incidence rate of HF hospitalization between the two groups.

Result
Male patients were younger (male vs, female; 71.5 years vs. 76.7 years, p&lt;0.001), greater in body weight (65.0 kg vs. 51.2 kg, p&lt;0.001), had lower pulse rate (77.5 bpm vs. 79.4 bpm, p=0.008), more often persistent/permanent type (52.0% vs. 48.2%, p=0.044), more likely to have previous stroke/systemic embolism (21.1% vs. 18.6%, p=0.039), diabetes mellitus (DM) (26.2% vs. 19.9%, p&lt;0.001), coronary artery disease (CAD) (16.0% vs. 12.3%, p&lt;0.001) and less likely to have prior HF (24.0% vs. 32.3%, p&lt;0.001), chronic kidney disease (CKD) (33.7% vs. 39.3%, p&lt;0.001) and had lower CHADS2 score (1.96 vs. 2.15, p&lt;0.001). In prescription data, male patients more often received oral anticoagulant (58.2% vs. 52.1%, p&lt;0.001) and less in diuretics. Systolic blood pressure, hypertension, prescription of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta blocker were comparable between the two groups.
During the median follow-up of 1,824 days, the incidence rate of HF hospitalization was lower in male than female group (male vs. female: 1.74 vs. 2.09 per 100 person-years, log rank p=0.005). On multivariate Cox regression analysis, age, sustained type of AF, prior HF, DM, CAD and CKD were significantly associated with an increased risk of HF hospitalization in male group. On the other hand, age, prior HF, DM, CKD were significantly associated with an increased risk of HF hospitalization but neither sustained type of AF nor CAD was in female group.

Conclusion
The incidence rate of HF hospitalization was lower in male patients than female patients. The risk factor associated with HF hospitalization were different between male and female in Japanese AF patients.
Prognostic value of monocyte-to-high-density lipoprotein-cholesterol ratio for all-cause mortality and heart failure in new-onset atrial fibrillation: a population-based cohort study
Authors: Tsang C T W , Ren Q W , Huang J Y , Chan Y H , Yiu K H 
Published: November 2023

Abstract

Background
A growing body of evidence suggests that inflammation plays a role in the onset and progression of atrial fibrillation (AF). Monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) has emerged as a novel and accessible biomarker that reflects both inflammation and oxidative stress. Previous studies have demonstrated the predictive value of MHR in several cardiovascular diseases including ischaemic stroke and acute coronary syndrome, but the association between MHR and adverse outcomes of AF remains unclear.

Purpose
With this study, we aimed to investigate the relationship of MHR with all-cause mortality and incident heart failure in patients with new-onset AF.

Methods
Patients with newly diagnosed AF from 1998-2021 (n=80,911) were included in this Hong Kong population-based cohort study. MHR was obtained by dividing fasting monocyte count by high-density lipoprotein-cholesterol, and patients were grouped according to MHR tertiles. We followed up patients until occurrence of outcomes, death or 1st September, 2022. The primary outcome was all-cause mortality, and the secondary outcome was incident heart failure. We evaluated the associations of MHR with all-cause mortality and heart failure both on a continuous scale using restricted cubic spline curves and by categories using multivariate Cox proportional hazards regression model.

Results
The median age of the cohort was 77.9 years old and 41,536 (51.3%) were male. Over a median follow-up of 3.7 years, 43,902 (54.3%) deaths and 14,114 (17.4%) incident heart failure occurred. The restricted cubic spline curves illustrated that MHR had a non-linear association with all-cause mortality and heart failure. Univariate Cox regression indicated that increased MHR at tertiles 2 and 3 were significantly associated with higher risks of all-cause mortality (HR: 1.06 [1.04-1.09], P&lt;0.001, 1.25 [1.22-1.28], P&lt;0.001, respectively) and new onset heart failure (1.07 [1.02-1.11], P=0.002, 1.23 [1.18-1.28], P&lt;0.001, respectively) when compared to those in tertile 1. MHR remained a significant predictor of mortality (tertile 2 HR: 1.06 [1.04-1.09], P&lt;0.001, tertile 3 HR: 1.22 [1.19-1.25], P&lt;0.001) and heart failure (tertile 2 HR: 1.06 [1.02-1.10], P=0.007, tertile 3 HR: 1.21 [1.16-1.26], P&lt;0.001) after multivariable adjustment.

Conclusion
MHR is a promising prognostic biomarker for all-cause mortality and heart failure in patients with new-onset AF.
Biomarkers for the prediction of cognitive decline in atrial fibrillation patients
Authors: Krisai P , Eberl M , Coslovsky M , Rodondi N , Chocano-Bedoya P , Kobza R , Moschovitis G , Rigamonti E , Beer J H , Mueller A , Reichlin T , Conen D , Osswald S , Bonati L , Kuehne M 
Published: November 2023

Abstract

Background
Patients with atrial fibrillation (AF) are at increased risk of cognitive decline. Biomarkers might help to identify the highest risk patients.

Purpose
To investigate associations of a broad panel of biomarkers with cognitive decline in a large population of AF patients.

Methods
We enrolled 1440 AF patients with available baseline biomarkers and cognitive testing by the Montreal Cognitive assessment (MoCA) score at inclusion and at ≥2 yearly follow-ups over three years. Cognition over time was assessed by modelling of a slope over three years. Cognitive decline was defined as a decreasing slope based on 1 standard deviation of the baseline MoCa score. We investigated the associations of biomarkers and age with cognitive decline in univariate logistic regression models by AUCs. We used Lasso modelling to build combined prediction models with biomarkers, clinical variables and both.

Results
Mean age was 72 years, 75% were male, 47% had paroxysmal AF and 90% were anticoagulated. During a follow-up of 3 years, cognitive decline occurred in 93 patients (6.5%). Patients with cognitive decline were older (77 vs 72 years, p=0.001), more often had paroxysmal AF (50 vs 47%, p=0.007) or a history of stroke (24 vs 11%, p=0.001), but there were no differences in anticoagulation (94 vs 90%, p=0.289). The three biomarkers with the highest univariate AUC for cognitive decline were Growth Differentiation Factor (GDF)-15 (0.67 [0.62-0.72]), Cystatin C (0.67 [0.61-0.72]) and high-sensitivity Troponin T (0.65 [0.60-0.70]), while age had the highest overall AUC (0.70 [0.64-0.75]) (Figure). The combined prediction model with the highest AUC of 0.69 (0.67-0.72) included GDF-15, age and baseline cognition.

Conclusion
Over 3 years, 6.5% of AF patients had cognitive decline despite a high rate of anticoagulation. Besides age, GDF-15, Cystatin C and high-sensitivity Troponin T had the highest predictive value for cognitive decline.Univariate AUCs for biomarker/ageFigure legend
Trajectories of walking speed in older adults with atrial fibrillation: a 15 year-follow-up population-based study
Authors: Okoye C , Calderon-Larranaga A , Qiu C , Xia X , Vetrano D 
Published: November 2023

Abstract

Background
Atrial fibrillation (AF), the most common arrhythmia in older adults, has been associated with frailty. However, the role exerted by AF in the long-term trajectories of functional decline still needs to be elucidated.

Purpose
The aim of the present study was to evaluate AF clinical impact on functional decline by tracing the evolution of the walking speed (WS) over 15 years of follow-up in a population-based cohort of older individuals.

Methods
This population-based cohort study included 3141 non-institutionalized participants (age ≥60 years; 63.6% women) from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) carried out in Stockholm, who were regularly examined from 2001–2004 to 2016-2019. AF was ascertained from clinical examination, electrocardiogram, and the Swedish National Patient Registry. Physical decline was assessed measuring participants mobility through the WS test (m/s). Participants WS was evaluated at baseline, and then followed up every 6 years (those aged &lt;78 years) or every 3 years (those aged ≥78 years). Incident heart failure, stroke and dementia were also recorded during the follow-up visits. The association between AF and WS trajectories was tested by multivariable joint models accounting for the longitudinal dropouts due to death. Analyses were also stratified by relevant individual characteristics after adjustment for clinically relevant covariates.

Results
At baseline, 285 (9.1%) participants were ascertained to have prevalent AF. Upon accounting for several potential confounders, we observed a faster annual WS decline in AF participants than in non-AF peers (β coefficient per year = −0.013, 95% confidence interval [CI]: −0.017 to −0.007) after multivariable adjustment for age, sex, education, dementia, COPD, diabetes, hypertension, heart failure, stroke, physical activity levels and BMI. The association was stronger in individuals 78+ than those younger than 78 years and in those without stroke, heart failure and higher engagement in physical activity (p per interaction &lt;0.05). In a secondary analysis carried out among participants who were free of heart failure, stroke, and dementia at baseline, controlling by incident heart failure, incident stroke, and incident dementia did not attenuate the association between AF and WS change.

Conclusion
AF is independently associated with a faster physical performance decline in older individuals Incident stroke, heart failure or dementia don’t seem to mediate the relationship between AF and mobility decline over time.
Pulmonary hypertension is an adverse risk factor for peri-procedural complications in patients undergoing cardioversion for atrial fibrillation
Authors: Kodali M , Atluri R , Yalamanchili S , Shoura S , Vardar U 
Published: November 2023

Abstract

Background
Atrial Fibrillation (AF) poses a significant burden on the American Healthcare system. Heart failure and AF commonly coexist in patients. Elevated left ventricular and atrial pressures result in progressive left atrial dilation and remodeling which in turn predisposes to the generation of AF. Many of these patients develop pulmonary hypertension (PHT) due to the remodeling and elevated left-sided pressures. Cardioversion (CV) for non-valvular atrial fibrillation (AF) is commonplace for patients during their initial presentation. Since many who undergo CV for AF could have PHT, we aimed to assess the periprocedural outcomes in this population.

Methods
We utilized the National Inpatient Sample from 2016-2019 to identify roughly 330,820 hospitalized adults who had CV for AF. These hospitalizations were further stratified based on the presence of PHT. A multivariate regression model was used to adjust for confounders and analyze the variables.

Results
Of those who underwent CV for AF, 45,345 (13.7%) had PHT. In-hospital mortality was interestingly lower in those with PHT (9.6% vs 10.37%; p&lt;0.001). Figure 1 shows the Forrest plot for multivariate analysis of in-hospital outcomes when adjusted for patient demographics, comorbidities, and hospital characteristics. When adjusted similarly, patients who underwent CV for AF and PHT had longer length of stay (LOS) by 2.11 days (p&lt;0.001) and had additional hospital costs (HC) of $29,470 (p&lt;0.001).

Conclusion
In this study, patients who underwent CV for AF with co-existing PHT had significantly worse outcomes in terms of LOS, HC, pulmonary embolism, atrial flutter, VT, SVT, AKI, and intubation. Of note, they interestingly had better outcomes in terms of in-hospital mortality, respiratory failure, and strokes. Returning the patient to sinus rhythm likely improved the left heart hemodynamics reducing post capillary pulmonary hypertension explaining the reduced mortality rate in this population. One major limitation of our study is the lack of outpatient follow up and the inability to differentiate between the different groups of PHT. Since several outcomes are worse in the setting of PHT, potential strategies for aggressive rate and volume control for those in AF should be pursued to avoid negative cardiac remodeling that would predispose to the development of PHT. AF patients with co-existing PHT should be aggressively monitored during hospitalizations as they have the potential to have worse outcomes.