bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of bleeding events on mortality in patients with atrial fibrillation and silent left atrial thrombi: insight from the LAT trial
Authors: Okada M , Tanaka N , Tanaka K , Hirao Y , Harada S , Miyazaki N , Iwasa K , Egami Y , Masuda M , Inoue K , Sunaga A , Hikoso S , Sakata Y 
Published: November 2023

Abstract

Background
Thrombolytic therapy is important to prevent thromboembolism in patients with atrial fibrillation (AF) and left atrial (LA) thrombi. However, bleeding complications are a major concern.

Purpose
To investigate the incidence and prognosis of bleeding complications in patients with AF and silent LA thrombi.

Methods
An analysis was performed from the LAT trial, a multicenter observational study investigating outcomes of silent LA thrombi detected by trans-esophageal echocardiography (TEE) in AF patients. Of 17,436 patients who underwent TEE, 297 (median age, 70 years; 31% female, median CHA2DS2-VASc score of 4) were eligible for inclusion. Management of oral anticoagulants was at the physician’s discretion, and the follow-up period was set as 1-year. Major bleeding was defined as intracranial hemorrhage, bleeding requiring surgery or transfusion, or ≥4 g/dl decrease in hemoglobin level.

Results
Prescription rates of oral-anticoagulants at baseline and the final follow-up were 81.8% and 89.9%, respectively (p = 0.002). During a median follow-up of 385 (interquartile range, 365-411) days after the thrombi detection, the incidence of thromboembolism, major bleeding, and all-cause death was 5.7% (n = 17), 11.4% (n = 34) and 8.4 % (n = 25), respectively. Patients with thromboembolism were more likely experience subsequent death than those without thromboembolism (17.7% vs. 7.9%, log-rank p = 0.063). Similarly, patients with major bleeding more frequently experienced subsequent death than those without bleeding (20.6% vs. 6.8%, log-rank p = 0.002). Time-adjusted Cox regression analysis revealed a temporal association between major bleeding and subsequent death (hazard ratio, 3.72; 95% confidence interval 1.55–8.93; p = 0.003) as well as between thromboembolism and subsequent death (hazard ratio, 2.98; 95% confidence interval 0.89–9.99; p = 0.077).

Conclusions
In the LAT trial, about 10% of patients with AF and silent LA thrombi experienced major bleeding during 1-year follow-up. Not only thromboembolism but also major bleeding was strongly associated with subsequent death.
Oral anticoagulation among frail patients with atrial fibrillation: assessment of net clinical benefit in a nationwide cohort
Authors: Nielsen P B , Jensen M , Hoejen A A , Larsen T B , Lip G Y H , Ording A G , Soegaard M 
Published: November 2023

Abstract

Background
Frail patients with atrial fibrillation (AF) are often undertreated with oral anticoagulants (OAC), and evidence for the net clinical benefit of OAC is sparse.

Objectives
We examined the risk of thromboembolic events and major bleeding, and the association between age, frailty level, and net clinical benefit (NCB) of anticoagulation.

Methods
This was an observational cohort study based on Danish nationwide data. Frail patients aged ≥50 years with a Hospital Frailty Risk Score ≥5 and incident AF were identified from 2013-2018. Patients were categorized according to OAC therapy, and differences in thromboembolic events and major bleeding were studied after 1 year. The NCB of anticoagulation was assessed by the bivariate trade-off between thromboembolism and bleeding.

Results
We identified 36223 frail AF patients (median age 79 years, 50.5% female), of whom 61.8% started OAC therapy, while 38.2% were untreated despite indication for stroke prevention. At one year, the risk of thromboembolic events was 2.1% (95% CI 1.8 to 2.3%) among patients not receiving OAC versus 1.5% (95% CI 1.4 to 1.7%) in patients with OAC. The one-year bleeding risk was 3.2% (95% CI 2.9 to 3.5%) among patients without OAC and 3.5% (95% CI 3.2 to 3.8%) among anticoagulated patients. The NCB was 0.66% (95% CI 0.19% to 1.12%) suggesting a statistically significant benefit of OAC treatment.

Conclusion
Frail AF patients are often untreated with OAC in routine clinical care despite an indication for stroke prevention. The NCB when balancing thromboembolic events and major bleeding was in favor of anticoagulation but decreased with advancing age and increasing frailty.
Haemorrhagic stroke among patients with atrial fibrillation: preceding oral anticoagulation use and 30-day case fatality over 10 years
Authors: Tiili P , Putaala J , Halminen O , Lehtonen O , Haukka J , Niemi M O , Mustonen P , Linna M , Hartikainen J , Airaksinen K E J , Lehto M 
Published: November 2023

Abstract

Background and purpose
Oral anticoagulation (OAC) is the cornerstone of thromboprophylaxis in atrial fibrillation (AF) yet complicated by elevated bleeding risk. We examined the temporal evolution of OAC treatment on 30-day fatality in patients with AF and first-ever hemorrhagic stroke (HS).

Methods
We identified the study population from the nationwide registry-linking Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study. Patients were eligible if the incident AF was diagnosed between January 2009 and November 2017, with a subsequent first-ever HS (ICD-10 I60* or I61*) recorded in hospital or death registries before December 2018. OAC purchases in the previous 90 days were registered.

Results
Over the ten-year period, 1,890 patients experienced their first-ever HS (53% women, median age 79.5 [IQR 72.5-85.5]). Of these, 1,039 (55%) had a recent OAC purchase. The 30-day case fatality was 45.4% (n=858, 57% women) and did not vary by prior OAC purchase (warfarin 47%, Non-Vitamin K Antagonist Oral Anticoagulants 41%, none 45%). The proportion of patients without OAC decreased from 67% to 34%, while case fatality increased between 2009 and 2011 from 42% to 54% and then decreased from 54% to 43%.

Conclusions
Despite the near-doubled proportion of patients with AF exposed to OAC prior to their first-ever HS, their 30-day case fatality rate decreased slightly over 10 years. These results suggest that the recent evolution of OAC treatment is associated with improved outcomes in the AF population.
Effect of perceived and objectively-assessed frailty on outcomes in edoxaban-treated patients with atrial fibrillation: data from the ETNA-AF-Europe 4-year follow-up
Authors: Fumagalli S , Diemberger I , Bakhai A , Pecen L , Lamparter M , Kirchhof P , De Caterina R 
Published: November 2023

Abstract

Background
Frailty is common in patients with atrial fibrillation (AF). However, different definitions of frailty are used, and these may variably overlap with frailty perception among physicians. Long-term data on outcomes based on perceived versus objective frailty in patients with AF treated with a non-vitamin K antagonist oral anticoagulant are lacking.

Purpose
To assess the effect of perceived versus objective frailty on outcome events in patients with AF treated with edoxaban during the 4-year follow-up of the ETNA-AF-Europe registry (NCT02944019).

Methods
ETNA-AF-Europe is a multinational, multicentre, post-authorisation, observational study conducted in patients with AF receiving edoxaban. In this sub-analysis, patients were evaluated in terms of perceived or objective frailty status (yes or no categories). Perceived frailty was based on investigators’ own clinical binary judgement in each patient. Objective frailty was determined using a Modified Frailty Index, a simplified adaptation of the Rockwood’s Frailty Index. Patient demographics and characteristics were collected at baseline. The efficacy and safety outcomes are reported here comparing frailty status (yes versus no) among perceived or objectively classified patients.

Results
Among the 13,164 patients with 4 years of follow-up, the prevalence of perceived and objective frailty was 10.7% and 4.1%, respectively. Compared with the objectively frail group, those perceived as frail were older, with a lower proportion of males, had lower body weight and creatinine clearance values, yet lower CHA2DS2-VASC and modified HAS-BLED scores (Table 1). Further, patients with objective frailty tended to have more comorbidities (e.g., diabetes, heart failure, hypertension; Table 1). Those deemed frail were more likely to receive the reduced 30 mg edoxaban dose versus non-frail patients (p&lt;0.001 for both groups), and non-recommended dosing regimens (60 or 30 mg) were more often prescribed in frail versus non-frail patients (p&lt;0.0001 for all comparisons; Table 1). Patients perceived as frail had a significantly higher risk of all evaluated outcomes compared with non-frail patients (p-value range: &lt;0.0001 – 0.0459; Figure 1). Similar data were seen for objectively frail patients, with the exception of no significant differences in the risk of intracranial haemorrhage (ICH, p=0.0918) or haemorrhagic stroke (p=0.1619; Figure 1).

Conclusions
Frailty was associated with an inappropriate dosing of edoxaban and an increased incidence of outcome events, quantitatively similar in the perceived and objective frailty groups. After 4 years of therapy, even if ICH risk was increased in frail subjects, its cumulative incidence was low.
Long-term effectiveness and safety of edoxaban in patients with atrial fibrillation: 4-year follow-up of more than 13,000 patients from the ETNA-AF-Europe study
Authors: Kirchhof P , Bakhai A , De Groot J R , Deharo J C , Levy P , Lopez-De-Sa E , Monteiro P , Steffel J , Waltenberger J , Fronk E M , Lamparter M , Laeis P , Smolnik R , De Caterina R 
Published: November 2023

Abstract

Background
Direct, non-vitamin K antagonist oral anticoagulants (DOACs/NOACs) have become the first-choice therapy for stroke prevention in patients with atrial fibrillation (AF) at risk of stroke. Data on long-term effectiveness and safety of NOACs are scarce and not available from randomised clinical trials.

Purpose
We analysed 4-year outcome data in 13,632 European patients with AF treated with the NOAC, edoxaban.

Methods
This is the first report of the four-year follow-up information collected in the ETNA-AF-Europe (NCT02944019) study. It is a prospective registry, conducted in 825 centres enrolling edoxaban-treated patients in 10 European countries. Design and follow-up were agreed with the European Medicines Agency as part of the post-approval safety assessment of edoxaban. Key efficacy and safety outcomes were adjudicated.

Results
13,164 patients (56.7% males) with AF treated with edoxaban (60 mg OD n=9617; 30 mg OD n=3042; missing dose n=505) were analysed: median (interquartile range [IQR]) age was 75 (68–80) years, weight 80 (70–90) kg, creatinine clearance (CrCl) 68.9 (52.7–87.9) mL/min, modified CHA2DS2-VASc and HAS-BLED scores 3 (2–4) and 2 (1–2), respectively in the overall population.
Annualised all-cause and cardiovascular deaths in the overall population were 4.1%/year and 1.0%/year, respectively; higher in the edoxaban 30 mg vs 60 mg cohort (Figure 1). Annualised rates of stroke, transient ischaemic attack and systemic embolic events rates were &lt;1% (0.6%/year, 0.3%/year and 0.1%/year, respectively); these proportions were similar between the two dose cohorts (Figure 1). The time-to-first event curves for all-cause death, stroke and major bleeding were almost linear throughout the 4-year follow-up (Figure 2), irrespective of dose cohort.
Compared with patients receiving edoxaban 60 mg, those prescribed 30 mg were older (median [IQR] age: 80 [75–85] vs 73 [66–78] years), had greater frail proportion (27.0% vs 6.6%), a lower CrCl (46.1 [37.4–59.0] vs 75.9 [61.9–93.8] mL/min) and a higher CHA2DS2-VASc score (4 [3–5] vs 3 [2–4]). Annualised bleeding rate was 3.0%/year and higher in the 30 mg vs 60 mg cohort (Figure 1). Annualised major bleeding, intracranial haemorrhage (ICH) and major gastrointestinal (GI) bleeding rates were low (0.9%/year, 0.2%/year and 0.4%/year, respectively), with higher major bleeding and major GI bleeding rates in patients treated with edoxaban 30 mg OD (Figure 1). ICH rates were similar in both dose cohorts.

Conclusion
These findings illustrate the long-term effectiveness and safety of edoxaban. Treatment with edoxaban over 4 years in patients with AF is associated with a relatively low, linearly increasing rate of all-cause death and ischaemic stroke. Rates of bleeding and especially ICH rates were low.
Sex disparities in outcomes of left atrial appendage occlusion
Authors: Ahmed R , Ramphul K , Deshpande S A U R A B , Sawatari H , Sherif A , Wafa E I , Mohammed S , Padmanabhan D E E P A K , Veillet-Chowdhury M R , Benton S , Schuler B , Khanji M , Chahal A 
Published: November 2023

Abstract

Background
Atrial fibrillation (AF) is the most common arrhythmia in adults and is associated with an increased risk of embolic stroke. Left atrial appendage occlusion (LAAO), such as Watchman device, has demonstrated non-inferiority to anticoagulation in clinical trials for prevention of stroke in non-rheumatic AF. However, sex differences in outcomes of LAAO implantation have not been studied using a large real-world database.

Purpose
To identify the sex disparities in outcomes of LAAO

Methods
Data from the 2016-2020 National Inpatient Sample (NIS) were used to identify patients of ages ≥18 with a primary diagnosis of atrial fibrillation/flutter and a primary/secondary procedure code for LAAO. Various patient characteristics, comorbidities, and complications were also identified and compared. Propensity-matched cohorts were extracted after adjusting for multiple comorbidities and demographics.

Results
A total of 87,790 procedures of LAAO were performed between 2016-2020, with 58.4% males and 41.6% females. Whilst a yearly rise in the number of procedures was also observed, the trend was not statistically significant (ptrend=0.318) (Figure 1). Post-matching 6,842 males and 7,303 females were retained in our study. Females had a higher mean CHA2DS2-VASc score (4.6 vs.3.7, p&lt;0.01) and longer length of stay than males (1.38 vs. 1.24 days, p&lt;0.01). Furthermore, a higher incidence of cardiac tamponade (1.1% vs. 0.3%, p&lt;0.01, aOR 3.642, 95% CI 2.231-5.946), need for mechanical ventilation (0.7% vs. 0.3%, p&lt;0.01, aOR 1.994, 95% CI 1.168-3.401), and pericardial effusion (3.9% vs. 2.8%, p&lt;0.01, aOR 1.359, 95% CI 1.124-1.643) were noted amongst females vs. males. Though post-procedure, females reported a higher incidence of acute kidney injury (2.2% vs. 1.9%, aOR 1.175, 95% CI 0.918-1.504, p=0.199), intra/post-operative haemorrhage (0.6% vs. 0.4%, aOR 1.635, 95% CI 0.981-2.726), and device failure (0.7% vs. 0.5%, aOR 1.118, 95% CI 0.692-1.806, p=0.650), this was not statistically significant. In addition, no differences were observed in the mean modified HAS-BLED score between the two groups (1.9 vs. 1.9, p=0.398) (Table 1).

Conclusions
By using a large propensity matched cohort of patients who have undergone LAAO procedure for AF, this study has demonstrated that length of stay, pericardial effusion, cardiac tamponade and need for mechanical ventilation are higher in females as compared to males. These findings necessitate the development of strategies to reduce the increased risk of adverse events for females.Figure 1
Safety and healthcare resource utilisation in patients undergoing left-atrial appendage closure - A nationwide analysis
Authors: Thevathasan T , Degbeon S , Paul J , Fuereder L , Gaul A L , Scheitz J F , Stadler G , Rroku A , Lech S , Buspavanich P , Huemer M , Reinthaler M , Landmesser U , Skurk C 
Published: November 2023

Abstract

Background
Percutaneous left-atrial appendage closure (LAAC) has emerged as a non-pharmacological alternative for stroke prevention in patients with atrial fibrillation (AF) not suitable for anticoagulation therapy. Real-world data on peri-procedural outcomes are limited.

Purpose
To analyse outcomes of peri-procedural in-hospital safety and healthcare resource utilisation after percutaneous LAAC.

Methods
The US National Inpatient Sample was utilised to identify AF patients undergoing LAAC from 2016 to 2019. Primary outcomes (safety) were in-hospital stroke or systemic embolism (SE), pericardial effusion (PE), major bleeding, device embolisation and mortality. Secondary outcomes (resource utilisation) were adverse discharge disposition, hospital length of stay (LOS) and treatment costs. Logistic and Poisson regression models were used to analye outcomes by adjusting for 10 confounders.

Results
11,240 adult patients (with 41.9% being female) with AF undergoing LAAC were included. SE decreased by 97% between 2016 and 2019 [95% Confidence Interval (CI) 0-0.24] (P=0.003), while a trend to lower numbers of other peri-procedural complications was determined. In-hospital mortality remained stable (0.14%). Hospital LOS decreased by 18% (0.78-0.87, P&lt;0.001) and adverse discharge rate by 41% (95% CI 0.41-0.86, P=0.005) between 2016 and 2019, while hospital costs did not significantly change (P=0.2). Of note, female patients had a higher risk of PE (OR 2.86 [95% CI 2.41-6.39]) and SE (OR 5.0 [95% CI 1.28-43.6]), while patients with multiple comorbidities had higher risks of major bleeding (P&lt;0.001), mortality (P=0.031), longer hospital LOS (P&lt;0.001) and increased treatment costs (P=0.073). Male patients had the most peculiar decrease in adverse discharge rate between 2016 and 2019: OR 0.45 [95% CI 0.27-0.77]. Significant differences in all outcomes were observed between male and female patients across US regions (Figure). Subgroup analyses confirmed that female patients had a prolonged LOS and higher risk of adverse discharge disposition than male patients.

Conclusions
LAAC has become a safer and more efficient procedure. Significant sex differences existed across US regions. Careful considerations should be taken when performing LAAC in female and comorbid patients.
Left atrial appendage occlusion indicated by increased thrombotic risk versus increased bleeding risk: a comparison of the stroke despite anticoagulation (STR-OAC) and EWOLUTION cohorts
Authors: Aarnink E , Maarse M , Fierro N , Tondo C , Pracon R , De Backer O , Nielsen-Kudsk J , Benito-Gonzalez T , Nombela-Franco L , Arzamendi D , Alla V , Swaans M , Vireca E , Bergmann M , Boersma L 
Published: November 2023

Abstract

Background
Left atrial appendage occlusion (LAAO) provides mechanical cardioembolic protection, especially attractive for atrial fibrillation (AF) patients that cannot use oral anticoagulation therapy (OAC). Patients with prior stroke despite OAC are at high risk for recurrence and may also benefit from LAAO as (adjunctive) therapy.

Purpose
To investigate the efficacy of LAAO in AF patients with prior stroke on OAC compared to LAAO in AF patients with a contra-indication to OAC.

Methods
The STR-OAC LAAO is an international collaboration combining patients that underwent successful percutaneous LAAO because of a thrombo-embolic event or LAA thrombus on OAC from multiple LAAO registries (n=439). This cohort was compared to patients from the previously published EWOLUTION registry comprising of patients that successfully underwent LAAO because of a contra-indication for long-term OAC (n=1005). Thrombotic endpoints were prespecified and (non-procedural) major bleeding was defined as BARC score&gt;2. Annualized event rates were calculated and compared to historical data based on individual patient risk scores.

Results
Both cohorts were comparable in terms of age and sex (Table 1). CHA2DS2-VASc and HAS-BLED scores were higher in the STR-OAC cohort. After LAAO indicated by a thrombotic event despite OAC, 33% of patients had a planned lifelong hybrid strategy approach of concomitant LAAO and OAC. Consequently, STR-OAC patients often continued OAC (with or without antiplatelet therapy), whereas EWOLUTION patients were more frequently discharged with antiplatelet therapy only. The annualized event rate (AER) for composite thrombotic events was slightly higher in the STROAC-LAAO compared to the EWOLUTION patients (4.2% versus 2.0%), possibly due to the higher thrombotic risk of this population. Major bleeding occurred more frequently in the EWOLUTION compared to STROAC-LAAO patients (AER 2.6% versus 1.1%, Table 2). In comparison to historically expected event rates, relative risk reduction (RRR) for thrombo-embolic events was 65% in the STR-OAC cohort, and 80% in the EWOLUTION cohort (Fig. 1). Annualized major bleeding rates were reduced with 81% and 46% in the STR-OAC-LAAO and EWOLUTION cohorts, respectively.

Conclusions
LAAO in AF patients with a thrombotic event despite OAC provides ischemic stroke protection similar to a guideline-recommended population with high bleeding risk. RRR for thrombotic events was more pronounced in the population contra-indicated for long-term OAC, while RRR for major bleeding was more pronounced in the patients that experienced a thrombotic event on OAC. Randomized trial data could endorse thrombotic event despite OAC as an indication for LAAO.Table 1&2Figure 1
Biatrial flutters: unique circuits requiring a customized ablation approach
Authors: Brito J , Valente Da Silva P , Alves Da Slva P , Martins A M , Nunes Ferreira A , Lima Da Silva G , Cunha N , Ricardo I A , Ribeiro J , Carpinteiro L , Cortez-Dias N , Pinto F J , Sousa J 
Published: November 2023

Abstract

Introduction
Atrial futters are macroreentrant tachycardias that typically involve several walls of a certain atrium, being the other atrium passively activated. Biatrial flutters (BAF) are peculiar macro-reentries associated with anterior/septal scars, involving both atria and using the interatrial connections.

Purpose
To characterize the mechanism of BAF a cohort of patients (pts) submitted to mapping and ablation.

Methods
Retrospective single-center study of pts with atypical atrial flutter submitted to ablation from 2015 to 2022. High resolution electroanatomical voltage and activation mapping were collected using Carto, Ensite or Rhythmia. Whenever the arrhythmia circuit was not fully displayed in a certain atrium, of the other atrium was mapped to fully characterize the reentrant circuit and establish the critical isthmus. Biatrial circuits were classified into 4 types: type 1, involving the mitral annulus and the tricuspid annulus, escaping the septal wall in both atria; type 2 using most of the mitral annulus and the right atrium (RA) septum; type 3, using both the left atrium (LA) and RA septum; and type 4, using most of the tricuspid annulus and the LA septum. Acute and long-term success was evaluated.

Results
From a total of 107 pts submitted to atypical flutter ablation, 5 pts presented BAF (3 male, median age: 55-yo), 4 of them previously submitted to cardiac surgery (CABG in 1, mitral valvuloplasty in 1, mitral+tricuspid valvuloplasty in 1 and surgical correction of aortic coarctation and ostium primum atrium septal defect in 1) and 1 had been previously submitted to pulmonary vein isolation (PVI), empirical roof line and cavotricuspid isthmus (CTI) ablation. A proximal-to-distal coronary sinus activation and extensive low-voltage areas at the septum were recognized in all these pts. The BAF mechanism was single loop in all of them, with a type 2 circuit in 2 pts, and types 1, 3 and 4 in one patient each. BAF types 1 and 4 were terminated with CTI ablation. BAF types 2 and 3 were terminated with linear ablations from the mitral annulus to the right superior PV, complemented with focal applications at Bachmann bundle insertion sites in the pts with type 2 BAF. Acute success was achieved in all pts. During a mean time of follow-up of 344±91 days, 1 pt had AFl recurrence.

Conclusion
BAF is a rare and complex arrhythmia, which is possible to ablate successfully by applying high-density mapping tools, a comprehensive analysis of the substrate/activation maps and a mechanism-tailored ablation strategy.