bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics of apixaban prescription in AF patients with single dose-reduction criterion: ASPIRE (efficacy and safety of apixaban in real-world practice in Korean frail patients with AF)
Authors: Choi J , Lee S R , Choi E K , Choi J I , Han S W , Oh S I 
Published: November 2023

Abstract

Background/Introduction
Previous observational studies reported that off-label underdosed apixaban might be associated with a higher risk of stroke. However, the real-world clinical practice data on the off-label underdosed apixaban in patients with atrial fibrillation (AF) who meet single dose reduction criteria remains scarce.

Purpose
This study aimed to evaluate the apixaban dosing pattern in patients with AF who met a single dose reduction criterion. The difference in clinical characteristics underlying the on-label and off-label underdose prescription of apixaban was also assessed.

Methods
The efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE) study is a multicenter, prospective cohort study. This study included patients with AF having a single dose reduction criterion of apixaban. Study subjects were categorized into two groups according to apixaban dose (on-label 5 mg twice daily [on-label], or off-label underdose 2.5 mg twice daily [off-label]). We evaluated the difference in the clinical characteristics were evaluated. Additionally, the ‘marginal zone’ was defined as age between 75 and 80 years, weight between 60 and 65kg, and creatinine level between 1.2-1.5mg/dL.

Results
A total of 1997 patients were included in this analysis (mean age 74.3±7.8 years, women 55.8%); 591 (29.7%) patients were 80 years or older, 1250 (62.6%) patients had body weight 60 kg or below, and 156 (7.8%) patients had serum creatinine 1.5mg/dL or higher. Of these patients, 1022 (51.2%) patients were prescribed off-label underdose apixaban. The off-label group was older and had higher mean CHA2DS2-VASC score, Charlson Comorbidity Index, and HAS-BLED scores than the on-label group. Hypertension, heart failure, prior bleeding history, chronic kidney disease, anemia, and concomitant antiplatelet agent usage were more prevalent in the off-label group, but prior stroke history was more common in on-label group. In the age ≥ 80 years group, the marginal zone serum creatinine was more prevalent in off-label group (p=0.011). In the body weight ≤ 60 kg group, the prevalence of marginal zone bodyweight and serum creatinine were higher in off-label group (p&lt;0.001 and p=0.02, respectively). In creatinine ≥ 1.5 mg/dL group, the proportion of marginal zone body weight were more common in off-label underdose group (p=0.001) (Figure).

Conclusions
Among AF patients with a single dose reduction criterion for apixaban, almost half of the patients were prescribed off-label underdose apixaban. Physicians were more likely to prescribe off-label underdose apixaban in patients with more frail characteristics, whereas on-label apixaban was preferred in patients with prior history of stroke. The clinical outcome of off-label underdose apixaban would be compared with the on-label standard dose in a future study.
Sleep apnea independently predicts incident atrial fibrillation in the young - Implications for targeted screening
Authors: Deb B , Vasireddi S K , Bhatia N K , Rogers A J , Clopton P , Narayan S M 
Published: November 2023

Abstract

Background
The risk factors predisposing to AF and ischemic stroke are not well defined in the younger population. That said, routine screening for neither obstructive sleep apnea (OSA) nor atrial fibrillation (AF) is recommended, although these risk factors comigrate. We hypothesized that OSA independently predicts AF in the young.

Methods
We mined electronic data from 2008 to 2022 from a large suburban academic and community healthcare system, for the endpoint of incident AF in 20-50Y adults. We related the endpoint to covariates including CHADSVASC components, OSA, race and socioeconomic factors prior to the diagnosis of AF, excluding patients with existing (prevalent) AF, hemorrhagic stroke, hypercoagulability and central sleep apnea.

Results
From an overall population of 1.7MM, we identified 765,645 aged 20-50Y. Of these, 7500 had OSA. In the follow-up period, 4833 young individuals (45 per 100K person-years) experienced incident AF. Sleep apnea [HR:5.16; (4.68, 5.68)] was the non-CHADSVASC strongest risk factor for incident AF, other than CKD [HR:3.74 (3.20,4.38)], Black race [HR:1.30 (1.16,1.46)], Hispanic ethnicity [HR:1.20; (1.10, 1.32)] and smoking [HR:1.32; (1.24, 1.41)] (Figure 1A). Within CHADSVASC, other than heart failure [HR:10.23; (8.94,11.80)], all the other components had lower hazards than sleep apnea (Figure 1B). The C-index of CHADSVASC score is 0.51 which is augmented to 0.65 (P&lt;0.05) with addition of OSA, CKD, race, ethnicity and smoking.

Conclusions
In a population of over 700 thousand 20–50-year-old adults, sleep apnea is a strong independent predictor for incident AF. This has implications for screening and therapy of young patients.
Relationship between corrected QT prolongation and new-onset atrial fibrillation in the general Japanese population
Authors: Ninomiya Y , Kawasoe S , Kubozono T , Tokushige A , Ichiki H , Kamada H , Yoshimoto I , Ikeda Y , Miyahara H , Tokushige K , Ohishi M 
Published: November 2023

Abstract

Background
The QT interval, an electrocardiogram (ECG) parameter, can be corrected for heart rate, giving the QTc. The QTc is an indicator of ventricular repolarisation and is widely used as a predictor of ventricular arrhythmia. Recent studies have reported a relationship between prolonged QTc and atrial fibrillation (AF) development.

Purpose
We investigated whether a relationship between QTc prolongation and new-onset AF could be identified in the general Japanese population.

Methods
This retrospective study evaluated the annual health check-up data of 103,304 adults (50,438 males; age, 54±15 years) that did not have AF at baseline, from April 2005 to October 2018. Most participants underwent annual health examinations as recommended by the Japanese health welfare policy. The QTc times were calculated with the Bazett formula (QTc=QT/√RR), using the mean QT and RR intervals. Participants were grouped according to QTc time: long-QTc group (males, &gt;440 ms; females, &gt;460 ms) and normal-QTc group. AF was diagnosed using a 12-lead surface ECG. Logistic regression analyses were performed to determine the strength of the association between prolonged QTc and new-onset AF. Multivariate analyses were adjusted for clinical variables (age, sex, obesity, hypertension, dyslipidaemia, diabetes, estimated glomerular filtration rate, and habitual drinking).

Results
The median follow-up time for the total study population was 6 years. During follow-up, 341 (0.3%) new cases of AF were recorded. Univariate analysis revealed a significant increase in new-onset AF in the long-QTc group (odds ratio [OR], 2.80; 95% confidence interval [CI], 1.85–4.25; p&lt;0.001). After adjusting for clinical variables, multivariate analysis revealed that a long QTc was significantly associated with new-onset AF (OR, 1.71; 95% CI, 1.12–2.61; p=0.013). In the multivariate analysis, age (OR, 1.06; 95% CI, 1.05–1.07; p&lt;0.001), sex (OR, 2.55; 95% CI, 1.95–3.33; p&lt;0.001), obesity (OR, 1.46; 95% CI, 1.16–1.84; p=0.001), and habitual drinking (OR, 1.90; 95% CI, 1.50–2.41; p&lt;0.001) were also significant predictors of new-onset AF.

Conclusions
Prolonged QTc is associated with an increased risk of new-onset AF in the general Japanese population. The mechanism of this causal relationship requires further investigation.
Repeated measurement of the novel atrial biomarker BMP10 improves risk stratification in anticoagulated patients with atrial fibrillation: Insights from the ARISTOTLE trial
Authors: Gkarmiris K I , Lindback J , Alexander J , Granger J , Kastner P , Lopes R , Ziegler A , Oldgren J , Siegbahn A , Wallentin L , Hijazi Z 
Published: November 2023

Abstract

Background
Atrial fibrillation (AF) increases the risk of stroke, heart failure, and death. Biomarkers provide important prognostic information about these complications in AF. Recently, bone morphogenic protein 10 (BMP10), a protein mainly expressed in atrial tissue, was identified as a novel marker in AF for the risk of ischemic stroke.

Purpose
To assess the association between baseline characteristics with BMP10 concentrations, and if repeated BMP10 measurements at 2 months improve the prognostication of ischemic stroke or systemic embolism and other cardiovascular events in patients with AF.

Methods
BMP10 was measured in plasma samples collected at randomization and at 2 months in patients with AF who were randomized to apixaban or warfarin in the ARISTOTLE trial (n = 2878) with a median follow-up time of 1.8 years. BMP10 was analyzed with a prototype Elecsys immunoassay. The association of baseline variables with BMP10 at 2 months was evaluated with linear regression analysis. Cox-regression models adjusted for baseline characteristics and comorbidities including kidney function and BMP10-level at baseline were used in order to evaluate associations with outcomes.

Results
Median age was 70 (63.0-76.0) and 63% were male. The events during the follow up period were 34 ischemic strokes, 155 deaths and 99 hospitalizations for heart failure. Median concentration of BMP10 was 2.4 ng/mL at inclusion and 2.6 ng/mL at 2 months (median increase 7.8%, p&lt;0.001). The Spearman correlation for BMP10 at baseline and 2 months was 0.71. The baseline variables most strongly associated with higher BMP10 levels at 2 months, in descending order of importance, were: higher BMI, female sex, worse kidney function, older age, AF-rhythm, diabetes, and randomized treatment. BMP10 levels at 2 months improved the risk stratification in models adjusted for clinical variables including baseline levels of BMP10. For ischemic stroke and death, the estimated associations were nonlinear (Figure) with increased risk with higher BMP10 levels (p=0.037 and p&lt;0.001, respectively), whereas the association with HF hospitalization was linear with HR of 1.91 (p=0.012) comparing the third and first sample quartiles. Patients randomized to apixaban had approximately 2.2% lower BMP10 levels at 2 months compared to those randomized to warfarin (p&lt;0.001).

Conclusions
In patients with AF, the level of the atrial biomarker BMP10 is consistently associated with the risk of stroke at baseline and after 2 months of treatment with warfarin or apixaban. Repeated compared to only one measurement of BMP10 further improves risk stratification. Apixaban as compared to warfarin is associated with a reduction in the BMP10 level, which is in accordance with the lower risk of stroke with apixaban as compared to warfarin.
Predictors of left ventricular reverse remodeling after catheter ablation for atrial fibrillation: sub analysis of a randomized controlled EARNEST-PVI trial
Authors: Sunaga A , Hikoso H , Tanaka N , Masuda M , Watanabe T , Inoue K , Matsuoka Y , Kida H , Sotomi Y , Dohi T , Okada K , Nakatani D , Sakata Y 
Published: November 2023

Abstract

Background
Atrial fibrillation (AF) is widely known to cause heart failure. The catheter ablation for AF improves left ventricular function in many patients with heart failure. However, the predictors of left ventricular reverse remodeling are not well established.

Purpose
The purpose of this study was to examine the predictor of left ventricular reverse remodeling in patients with persistent AF.

Methods
The predictors of left ventricular reverse remodeling was examined using data from EARNEST-PVI trial which compared 12-month rhythm outcomes between persistent AF patients allocated to pulmonary vein isolation (PVI) alone and those allocated to PVI followed by left atrial linear ablation or complex fractionated electrograms ablation. Left ventricular reverse remodeling in this study was defined as a 15% reduction of left ventricular systolic diameter at transthoracic echocardiogram 12 months after initial ablation compared to preoperative echocardiogram.

Results
Of the 512 patients enrolled in the EARNEST-PVI trial, 453 patients with preoperative and 12-month postoperative echocardiogram data were analyzed. Median age was 67 [60. 73] years and 75.7% were male. Recurrence of AF was observed in 106 patients (23.4%) during 12 months after the ablation. LVEF before the initial ablation was 44 [39, 47]% and LVEF 12 months after the initial ablation was 60 [55, 63]% (P&lt;0.001), and LVDs before the initial ablation was 30 [27, 34] mm and LVDs after the initial ablation was 29 [27, 31] mm (P&lt;0.001). Left ventricular reverse remodeling was observed in 78 patients (17.2%). Multivariate linear regression analysis showed age (Odds ratio 0.967 [95%CI=0.939-0.996], P=0.025), preoperative hear rate (Odds ratio 1.032 [95%CI=1.018-1.047], P&lt;0.001) and the use of β-blocker (Odds ratio 2.119 [95%CI=1.235-3.638], P=0.006) were independently associated with left ventricular reverse remodeling but AF recurrence was not (Odds ratio 0.532 [95%CI=0.425-1.561], P=0.538).

Conclusion
Patients with persistent AF showed improvement of LVEF and left ventricular reverse remodeling 12 months after the catheter ablation. Age, heart rate before the initial ablation and the use of β-blocker were predictive factors for the left ventricular reverse remodeling after the ablation regardless of AF recurrence.
Influence of heart failure and chronic kidney disease on cardiovascular outcome in patients with atrial fibrillation - insights from a cohort study of 7,412 patients
Authors: Baumer U , Pedarnig L , Hammer A , Steinacher E , Kazem N , Koller L , Hengstenberg C , Sulzgruber P , Niessner A , Hofer F 
Published: November 2023

Abstract

Background
Heart failure (HF) and chronic kidney disease (CKD) form a vicious circle, reinforcing each other’s disease development and progression and causing higher rates in both morbidity and mortality. Here, we aimed to investigate the relationship between these two prevalent and interrelated diseases in an unselected patient population with AF.

Methods
This analysis includes patients with known AF, treated at a tertiary center between 07/2000 and 07/2019. The primary combined endpoint was hospitalization for heart failure (HHF) or cardiovascular (CV) death. We used cox regression models adjusted for age, sex, diabetes, coronary artery disease, hypertension, BMI and CRP-levels.

Results
We examined 7412 patients with AF and followed them over a median of 5.3 years. The median age was 70 years (IQR 61 to 78 years) and 2,945 (39.7%) were female. 434 (5.0%) patients had known CKD, 1,296 (17.5%) patients had HF, and 372 (5.4%) patients had both CKD and HF. There was a significant stepwise increase in event rates for the composite of CV death/HHF among patients without CKD or HF (KM event rate at 5 years: 23%), patients who had HF but no CKD (KM event rate at 5 years: 61%), patients with CKD but no HF (KM event rate at 5 years: 63%), and those who had both, HF and CKD (KM event rate at 5 years: 82%; P-logrank &lt;0.001; Figure 1A). After multivariable adjustment, both CKD (with an adjusted hazard ratio of 2.22 and a 95% confidence interval of 1.87 to 2.63) and HF (with an adjusted hazard ratio of 2.53 and a 95% confidence interval of 2.26 to 2.84) were significantly associated with CV death/HHF and exerted a similar magnitude of the relationship. Patients with concomitant disease had the highest risk of the primary endpoint (with an adjusted hazard ratio of 3.96 and a 95% confidence interval of 3.34 to 4.68; Figure 1B).

Conclusion
AF patients with CKD and HF are at very high risk of CV death/HHF. Commonly used risk scores usually focus on stroke as the most dreaded complication in patients with AF. These findings suggest that the influence of CKD and HF expand beyond the risk of stroke to CV death/HHF in an unselected AF patient population.Figure 1
Predictors of single shot pulmonary vein isolation with Heliostar radiofrequency balloon
Authors: Martinez Gomez E , Salgado Aranda R , Calvo Cuervo D , Gonzalez Ferrer J J , Canadas Godoy V , Filgueiras Rama D , Chavez Ortiz I , La Rosa G , Sanchez Vallejo C , Perez-Villacastin Dominguez J , Perez Castellano N 
Published: November 2023

Abstract

Introduction
Single shot pulmonary vein isolation techniques have emerged as an effective and safe alternative to point-by-point ablation, considerably reducing procedure times. The recent appearance on the market of the Heliostar® radiofrequency (RF) balloon offers a new option in this regard. The main predictors of single-shot isolation with this new device are unknown.

Objectives
Our objective was to evaluate as potential predictors of single-shot isolation the impedance drop, temperature rise and voltage reduction of the electrograms recorded by the balloon during radiofrequency application.

Methods
A total of 25 patients with paroxysmal (68%) or persistent (32%) symptomatic atrial fibrillation were prospectively included and underwent pulmonary vein isolation with Heliostar® RF balloon. Impedance and temperature parameters were collected from each of the applications performed in all veins. The voltage of the electrograms recorded by the Heliostar® RF balloon immediately before and after initiating the RF application in each vein was collected. The number of applications per vein was recorded and the single shot criterion was discriminated in each vein. A total of 92 veins were included for impedance and temperature analysis, and 59 veins for electrogram analysis (excluding veins in which the RF application was performed in atrial fibrillation). Impedance drop, temperature increase and electrogram voltage decrease during each application were analysed by logistic regression to correlate these parameters as potential predictors of single shot isolation.

Results
Single shot isolation was obtained in 64.1% of the veins. Applications that obtained persistent single shot isolation showed a higher impedance drop [22.5 ± 6.3 Ω vs 19 ± 5.3 Ω, p = 0.005] and a higher temperature rise [12.5 ± 4.4 ºC vs 10.3 ± 3.5 ºC, p = 0.008]. The voltage reduction of the electrograms collected by the balloon, on the other hand, did not differ significantly between the two groups [2.3 mV in single shot vs 2.2 mV in non-single shot applications, p = 0.4]. Univariate analysis by logistic regression showed impedance drop [OR per 1 Ω increase, 1.11, 95% CI 1.02-1.21, p = 0.007] and temperature increase [OR per 1°C increase, 1.15, 95% CI 1.02-1.3, p = 0.01] as significant predictors of single shot isolation.

Conclusions
Impedance drop and temperature rise during application were significant predictors of single shot isolation with Heliostar® RF balloon. The voltage reduction of the electrograms recorded by the balloon was not a predictor of single shot application.
Early pulmonary vein isolation in patients with heart failure
Authors: Toth P , Arnoth B , Komlosi F , Vamosi P , Szegedi N , Sallo Z , Perge P , Osztheimer I , Merkely B , Geller L , Nagy K V 
Published: November 2023

Abstract

Background
Atrial fibrillation (AF) and heart failure (HF) are often present simultaneously, leading to worse outcomes compared to the respective morbidity alone. Pulmonary vein isolation (PVI) is the most effective treatment modality and should be considered as first-line therapy, however, the optimal timing of the procedure is still unknown.

Purpose
We aimed to investigate the effect of early PVI on all-cause mortality and AF recurrence in patients with HF.

Methods
The data of 334 patients with symptomatic paroxysmal (n=118, 35.5%) or persistent (n=212, 63.5%) AF and HF with LVEF &lt; 50% were analyzed, who underwent PVI using radiofrequency energy between 2010 and 2022. All available medical data of the patients were collected in a structured registry. Early PVI was defined as catheter ablation performed within 12 months of AF diagnosis. The median follow-up was 1524.5 [365.0-3939.0] days with a minimum of 365 days. Our primary endpoints were all-cause mortality and AF recurrence following 3-months blanking period.

Results
During the follow-up of the 334 patients, 164 (49.1%) experienced AF recurrence and 86 (25.8%) patients died. The median age was 64 [56.1-69.9] years. The median LVEF was 40% for early PVI and 38% for deferred PVI (p=0.057). Out of the 139 (41.6%) patients who underwent early PVI, 36 (25.9%) had AF recurrence and 83 (59.7%) were taking amiodarone. Patients who underwent early PVI had longer freedom from recurrence (median 1042.5 [474.8-1921.0] days for early PVI, median 424 [134.5-1153.0] days for deferred PVI). Early PVI predicted lower rate of AF recurrence (HR: 0.29, p&lt;0.0001). Early ablation was not associated with mortality benefit. Among those who experienced AF recurrence, a repeat ablation was associated with better survival (HR: 0.29, p&lt;0.0001).

Conclusions
Our study shows that early rhythm control therapy with catheter ablation may be more beneficial compared to deferred PVI in patients with AF and HF. A repeat ablation may be considered in case of arrhythmia recurrence in patients with AF and HF to reduce mortality.
Safety and efficacy of non-vitamin K antagonist oral anticoagulants compared to warfarin in patients with atrial fibrillation and end stage renal disease: a meta-analysis of randomized trials
Authors: Chao T , Lip G Y H , Chen S A 
Published: November 2023

Abstract

Background
Stroke prevention in patients with atrial fibrillation (AF) and end stage renal disease (ESRD) is difficult because of the lacking of high-quality evidence. Although there were few randomized trials comparing NOACs and warfarin in AF patients with ESRD, the small patient size prohibits these studies from making a conclusion. We aimed to perform a meta-analysis to evaluate currently available randomized trials in this special population.

Methods
We searched the literature for randomized clinical trials comparing NOAC to warfarin in AF patients with ESRD undergoing hemodialysis.

Results
A total of 3 randomized trials were identified from the literature (one for rivaroxaban [Valkyrie study] and two for apixaban [AXADIA-AFNET 8 and RENAL-AF]). About the principal efficacy outcome, NOACs did not decrease the risk compared to warfarin (relative risk [RR] 0.79, 95%CI 0.45-1.37) while a significant heterogeneity was noted (p = 0.03). In Valkyrie study, rivaroxaban had better efficacy outcome than warfarin (RR 0.57, 95%CI 0.43-0.75). For the safety outcome, the risk was similar between NOACs and warfarin (RR 0.81, 95%CI 0.52-1.27) without significant heterogeneity (p = 0.11)(Figure 1). The pooled event rate of 3 trials disclosed a high risk of all-cause mortality (39.9% for NOACs, 34.6% for warfarin) and cardiovascular mortality (10.1% for NOACs, 8.5% for warfarin) for AF patients with ESRD even on OACs (Figure 2).

Conclusions
This meta-analysis suggested that NOACs (rivaroxaban or apixaban) was at least as safe and effective as warfarin in AF patients with ESRD. Even on OACs, these patients remain at high risk of cardiovascular events and all-cause mortality. Integrated care and holistic management were important for this high-risk population.