bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictability of noninvasive liver fibrosis score for cardiac events in patients with nonalcoholic fatty liver disease
Authors: Shibata N , Ito T , Toyoda H , Tanaka A , Morita Y , Kanzaki Y , Watanabe N , Yoshioka N , Morishima I 
Published: November 2023

Abstract

Background
Patients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of cardiac events. Although the severity of liver fibrosis is related to worsening prognosis in patients with NAFLD, it is unclear whether the noninvasive liver fibrosis score has a predictive value for cardiac events.

Purpose
To investigate the relationship between noninvasive liver fibrosis score and the future risk of cardiac events.

Methods
Among 13,368 patients with NAFLD diagnosed using ultrasonography, 4,071 patients were evaluated. Liver fibrosis was assessed and divided into three groups based on the Fibrosis-4 (FIB4) index (cut-off value of 1.30 and 2.67) and NAFLD fibrosis score (NFS) (cut-off values of -1.455 and 0.676), respectively. The primary outcome of this study was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease.

Results
The median age of the evaluated patients was 61 [52–69] years, and 2,201 [54.1%] were male. After a median follow-up period of 6.6 years, 179 (4.4%) patients experienced MACE. Kaplan–Meier survival analysis demonstrated that MACE increased progressively with theFIB4 index (log-rank, p &lt; 0.001) and NFS (log-rank, p &lt; 0.001). Multivariable analysis showed that the higher the FIB4 index, the higher the risk for MACE (compared to the group [reference] with low FIB4 index values, hazard ratio [HR] was 1.860 for the group with intermediate FIB4 index values [95% confidence interval (CI), 1.326–2.610; p&lt;0.001] and 3.325 for the group with high FIB4 index values [95% CI, 2.017–5.479; p&lt;0.001]), and the higher the NFS, the higher the risk for MACE (compared to the group [reference] with low NFSvalues, HR was 1.938 for the group with intermediate NFS values [95% CI, 1.391–2.699; p&lt;0.001] and 3.492 for the group with high NFSvalues [95% CI, 1.997–6.105; p&lt;0.001]).

Conclusions
The FIB4 index and NFS impacted the predictability of MACE in patients with NAFLD.Kaplan–Meier analysis for MACE
Fully automated quantitative stress perfusion cardiac MRI to assess myocardial perfusion in adult patients with convalescent Kawasaki disease and coronary aneurysms: an age and sex-matched analysis
Authors: Cheng K , Bolland M , De Silva R 
Published: November 2023

Abstract

Introduction
Coronary aneurysms are a well-documented complication of childhood Kawasaki disease. They may persist into adulthood predisposing to impaired myocardial blood flow, symptoms, and adverse cardiovascular events. Preliminary reports suggest that Kawasaki disease may also be associated with coronary microvascular dysfunction. The effect of coronary involvement from Kawasaki disease on myocardial perfusion in convalescent asymptomatic adults has not been studied using fully automated inline quantitative perfusion MRI (CMR).

Purpose
To assess the effect of coronary artery abnormalities on quantitative myocardial perfusion in adult patients with convalescent Kawasaki disease compared to an age and sex-matched control cohort.

Methods
Retrospective single centre cohort analysis of adult patients with convalescent Kawasaki disease who have undergone fully automated inline quantitative myocardial stress perfusion CMR. All patients had coronary involvement during their acute childhood illness. An age and sex-matched group (n=14) with normal CMRs was selected for comparison. Rest MBF was corrected for heart rate by dividing by the scan heart rate and multiplying by the mean resting heart rate among all subjects. A per-vessel analysis was performed using a linear mixed effects model with pairwise comparisons to assess the effect of coronary abnormalities (normal, aneurysmal with or without thrombosis, revascularised) on myocardial perfusion reserve (MPR).

Results
28 patients were included (14 Kawasaki; 14 controls). All patients in the Kawasaki cohort had assessment of coronary anatomy either by CT (93%) or invasive (7%) coronary angiography. A total of 84 vessels were analysed. Mean age and sex were well matched (Kawasaki: 27±6.2 years; 13 males : 1 female vs. controls: 27±6.4 years; 13 males : 1 female). In patients with Kawasaki disease, thrombosed aneurysmal arteries were associated with a significantly impaired MPR compared to normal (mean Δ: -0.817; P=0.003) and aneurysmal (mean Δ: -0.957; P&lt;0.001) arteries. MPR in aneurysmal and revascularised arteries were not significantly different from normal arteries in patients with Kawasaki disease. There was no significant difference in MPR between normal coronary arteries in patients with Kawasaki compared to controls.

Conclusions
Thrombosis in coronary aneurysms was associated with a significant impairment of myocardial perfusion in adult patients with convalescent Kawasaki disease. There was no significant reduction in perfusion in territories supplied by normal or aneurysmal arteries which does not support coronary microvascular dysfunction in these patients. Further studies are needed to confirm these preliminary findings.
Cross-sectional analysis of demographic and clinical characteristics of patients using icosapent ethyl
Authors: Nelson J , Toth P , Soran H , Ganda O , Hannachi H , Wong N , Abrahamson D , Hartman J , Philip S 
Published: November 2023

Abstract

Background/Introduction
Icosapent ethyl (IPE) is an ethyl ester of eicosapentaenoic acid first approved in 2012 in the United States for the treatment of severe hypertriglyceridemia (triglyceride [TG] levels ≥500 mg/dL).1 Following results from the global REDUCE-IT trial in 2019 in which IPE substantially reduced the risk of cardiovascular (CV) events,2 IPE was approved in European countries and the United States to reduce the risk of CV events in adults treated with statins who have elevated TG levels (≥150 mg/dL) and established CV disease (CVD) or diabetes mellitus (DM) with additional risk factors for CVD.1,3 An estimated 3 million American adults are eligible to receive IPE for primary and secondary CVD prevention.4

Purpose
Provide the first descriptive study of demographic and clinical characteristics of US patients taking IPE.

Methods
A database with electronic medical records of &gt;89 million patients from 56 US health care organizations was used to identify those taking IPE, defined as those for whom at least 2 IPE prescriptions were documented (ie, on 2 separate dates). No specific date range or exclusion criteria were applied. Patient demographic information, prior/existing conditions, prior/concomitant medications, and laboratory data were retrieved.

Results
As of January 19, 2023, a total of 40,408 patients taking IPE were identified; they had a mean (SD) age of 60.3 years (12.9) and a body mass index of 31.9 kg/m2 (6.07). Most patients started taking IPE after January 1, 2019 (72.8%), were men (60.5%), White (75.2%), non-Hispanic or Latino (73.1%), and from the southern (46.0%) or northeastern (34.0%) United States (Table). In line with the indication of IPE, 65.3% had prior atherosclerotic CVD or DM and at least 1 risk factor. Common prior or existing conditions associated with those indicated for IPE treatment were DM (41.0%), coronary artery disease (30.2%), prior myocardial infarction (11.0%), prior stroke (7.4%), and severe hypertriglyceridemia (8.1%); hypertension (68.4%) and obesity (40.9%) were common comorbidities. Mean (SD; median) TG level in the 3 months before IPE initiation was 422 mg/dL (506; 300). Treatment with statins was very high (71.8%), and common other concomitant medications included anticoagulants (53.3%), antidiabetic agents (52.3%), and antiplatelets (46.0%; Table). Fibrates were used by 26.0% of patients taking IPE any time on or before IPE initiation.

Conclusion(s)
Patients using IPE commonly had a history of CVD, DM, or both, took statins, and had elevated levels of TG, thereby meeting the indication for IPE treatment. The high baseline TG levels in this population suggest that IPE is underutilized.
Early repeat ablation strategy in atrial fibrillation patients is associated with lower recurrence rates
Authors: Toennesen J 
Published: November 2023

Abstract

Introduction
Atrial fibrillation (AF) ablation at early stages of AF improves the ablation outcomes in de novo ablations. Whether this is true in repeat ablations is unknown. Therefore, data pertaining the impact of early repeat ablation on AF recurrence in large, unselected cohorts is highly warranted.

Purpose
To examine AF recurrence after repeat ablation by time from recurrent AF to repeat ablation.

Method
Using Danish nationwide registries, all Danish patients above 18 years who underwent repeat AF ablation from January1st 2010 to December31st 2018 were identified and included at the date of repeat ablation. Exposure of interest was time from recurrent AF after de novo ablation to repeat ablation. The primary outcome was recurrent AF, defined from using a composite endpoint comprising claimed prescriptions of AAD, hospital admissions due to AF, re-ablation, or electrical cardioversions. The cumulative incidence of recurrent AF by time from recurrent AF to repeat ablation at 5-year follow-up after a blanking period of 90 days, was estimated using the Aalen-Johansen estimator, taking death as a competing risk into account. The Hazard Ratios of recurrent AF by time from recurrent AF to repeat ablation were examined using Cox models adjusted for sex, age, procedure-year, heart failure, ischemic heart disease, chronic obstructive pulmonary disease, and hypertension. Sub-group analysis of the impact of procedural year and AF-type (paroxysmal vs persistent) were made.

Results
The study cohort consisted of 2,704 patients. Median age [IQR] was 63 [55, 68] in the early ablation group (repeat ablation within 0.5 year after recurrent AF) and 65 [58, 70] in the late ablation group (repeat ablation at least 0.5 year after recurrent AF). It was predominately males and paroxysmal AF patients accounted for 62% and 59% in early vs late repeat ablations. Patient characteristics regarding left atrium size, left ventricular ejection fraction, and body mass index were relatively similar. Prior use of amiodarone was slightly higher in the early ablation group, while use of class 1C antiarrhythmics was highest in the late ablation group.
A total of 1,625 (60%) patients had recurrent AF within 5 years after the blanking period. The mean follow-up time was 874 days.
The cumulative incidence (95% CI) of recurrent AF was 54.8% (52.4%, 57.2%) and 67.3% (64.5%, 70.2%) in the early and late repeat ablation groups respectively. (Figure 1)
The HR (95% CI) for the late repeat ablation group was 1.25 (1.10, 1.41) with the early repeat ablation group as reference. (Figure 2)

Conclusion
Among 2,704 patients undergoing repeat AF ablations from 2010-2018, we found that early repeat ablation was associated with significantly lower recurrence rates. Therefore, early repeat ablation could potentially provide substantial benefits and improve outcomes, indicating repeat ablation as first-line therapy might be ideal.
Baseline characteristics and outcomes of extended oral anticoagulant treatment in patients with venous thrombosis: a retrospective cohort study in France
Authors: Chaves J , Pesce G , Gusto G , Quignot N , Khachatryan A , Subash R , Mokgokong R 
Published: November 2023

Abstract

Background
Guidelines recommend anticoagulant (AC) extended treatment for patients with unprovoked VTE or VTE provoked by permanent risk factors (ESC 2019, CHEST 2021). A recent observational study has shown that apixaban extended treatment (&gt;6 months) vs no extended treatment in patients with venous thromboembolism (VTE), regardless of risk factors, is associated with decreased risk of recurrent VTE (rVTE), with no increase in major bleeding. A better safety profile for patients receiving apixaban vs those receiving vitamin K antagonists (VKAs) was also observed.

Purpose
To describe characteristics of patients with VTE receiving AC extended treatment (&gt;6months) vs those receiving acute treatment only (&lt;6 months). Outcomes among patients receiving extended treatment with apixaban and VKAs were also reported.

Methods
The presence of risk factors were assessed in a nationwide retrospective cohort study of AC treatment-naïve adult patients (identified via the French national health data system: SNDS) with VTE, who were prescribed VKAs or apixaban from 2013 to 2018. Descriptive statistics for patients receiving AC extended treatment vs those receiving only acute treatment are presented. Risk of bleeding (based on principal diagnoses of hospital stays), rVTE (based on principal diagnosis of hospital stays and specified procedures), and all-cause mortality were assessed 18 months following the initiation of extended treatment using inverse probability treatment weighted (IPTW) analysis to balance baseline socio-demographic and clinical characteristics.

Results
21,215 VTE patients who initiated AC treatment were included: 10,775 VKAs (41.5% acute vs 58.5% extended treatment) and 10,440 apixaban (44.5% acute vs and 55.5% extended treatment). A higher proportion of apixaban and VKA patients with permanent risk factors (apixaban: 57.7%; VKAs: 57.7%) or unprovoked VTE (apixaban: 56.8%; VKAs: 59.7%) received extended treatment vs acute treatment only. Table 1 shows the adverse clinical outcomes assessed during extended treatment in IPTW balanced cohorts. Compared to patients treated with VKAs (n=6151), patients treated with apixaban (n=5682) had lower rates of rVTE (1.89 vs 2.84 per 100 person-years), bleeding (1.11 vs 1.69 per 100 person-years) and all-cause mortality (2.70 vs 6.74 per 100 person-years).

Conclusions
A slightly higher proportions of patients with permanent VTE risk factors and unprovoked VTE received extended treatment compared to acute treatment. Consistent with guidelines, there persists a need to increase these rates when clinically indicated to improve patient outcomes. Clinical event rates were numerically lower for apixaban compared to VKAs, which suggests clinical benefit for apixaban. However, more robust confirmatory analyses are required.
Risk and benefits of baseline antiplatelet therapy in 58,598 patients with atrial fibrillation randomized to NOACs vs warfarin
Authors: Patel S , Palazzolo M G , Antman E M , Braunwald E , Carnicelli A P , Connolly S J , Granger C B , Patel M R , Wallentin L , Ruff C T , Giugliano R P 
Published: November 2023

Abstract

Background
The efficacy and safety of NOAC versus warfarin (W) may differ in AF pts receiving antiplatelet therapy (APT) at baseline. Moreover, prior individual trial-specific analyses examining the treatment effect of NOAC vs. W as a function of APT are underpowered for interaction testing.

Purpose
We evaluated outcomes by randomized anticoagulant stratified by baseline APT in a pooled individual pt-level meta-analysis of 4 pivotal RCTs of NOAC vs. W in AF: RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48.

Methods
Pts were stratified by use of APT vs. no APT at baseline. Pts randomized to low-dose NOAC not globally approved (edoxaban 30/15 mg or dabigatran 110 mg) were excluded. The primary efficacy and safety outcomes were stroke/systemic embolic events (S/SEE) and major bleeding, respectively; ischemic stroke (IS), intracranial hemorrhage (ICH), major GI bleeding and all-cause mortality (ACM) were secondary outcomes. Each outcome was assessed by randomized treatment using a Cox model stratified by trial with adjustment for age, sex, weight, CrCl, smoking status, HTN, DM, CAD, prior MI, PAD, and prior stroke. Interaction testing was performed by APT at baseline.

Results
Of 58,598 pts, 19,774 (34%) were on APT at baseline (92% aspirin only, 5% P2Y12 only, 3% DAPT). Pts treated with APT had greater prevalence of CAD (41% vs. 24%), prior MI (22% vs. 11%), and PAD (6% vs. 4%) (p&lt;0.001 for each). Reflective of these baseline differences, the annualized event rate for each outcome was higher in the APT vs. no APT group (Figure). The treatment effect (HR) of NOAC vs. W for all 6 clinical outcomes was consistent irrespective of baseline APT (p-interaction [aHR] for each = NS; Figure). However, the absolute risk reduction (ARR) for NOAC vs. W differed for ICH and major GI bleeding as a function of baseline APT (Figure). Specifically, for ICH, a greater absolute benefit was seen with NOAC vs. W in those on APT at baseline (ARR 0.6% vs. 0.3%; p-int = 0.007). Conversely, for major GI bleeding, NOAC vs. W was associated with greater absolute risk in those on APT (ARR -0.6% vs. -0.2%; p-int = 0.04).

Conclusions
The treatment effect of NOAC vs. W is consistent irrespective of APT at baseline for S/SEE, major bleeding, and ACM. Given higher rates of bleeding in AF pts treated with both APT and anticoagulation, concomitant APT should be avoided when possible. In pts requiring concomitant APT, NOAC instead of W should be considered owing to greater absolute safety benefit for ICH, which should be weighed against individual patient-specific risk factors for GI bleeding.
Comparative effectiveness and safety of apixaban and low-molecular weight heparin among patients with venous thromboembolism and active cancer in an extended treatment setting
Authors: Cohen A T , Dhamane A D , Liu X , Han S , Stellhorn R , Zhang Q , Singh R , Wang J , Luo X 
Published: November 2023

Abstract

Background
The 2020 European Society of Cardiology guidelines recommend extended anticoagulant (AC) treatment among patients with VTE and with progressive or persistent risk factors (such as cancer) as they are at a high risk of a recurrent VTE episode.

Purpose
The study evaluated the risk of recurrent VTE and major bleeding (MB) among patients with VTE and active cancer prescribed apixaban or LMWH (reference) for ≥3 months.

Methods
This retrospective study included patients ≥18 years with VTE who initiated apixaban or LMWH within 30 days following the first VTE event using a large administrative claims database, representing ≥140 million patients enrolled in US health plans. Data from July 1, 2016, through April 30, 2022, was used. Patients were required to have ≥3 months of continuous enrollment (CE) and ≥3 months of continuous primary AC treatment following the date of apixaban/LMWH initiation. The end of 3 months of primary treatment was designated as index date. The follow-up period was from the day after the index date until the earliest of disenrollment, discontinuation of index anticoagulant, switch to another anticoagulant, or the end of the study period. The MB and recurrent VTE outcomes were evaluated and compared in the follow-up period. Inverse-probability treatment weighting (IPTW) was used to balance the treatment cohorts on relevant demographic and clinical characteristics including VTE and cancer-related variables. Incidence rate for the outcomes were calculated per 100 person-years. Cox proportional hazard models were used to evaluate the adjusted risk of recurrent VTE and MB reported as hazard ratios (HR) along with 95% confidence interval (CI).

Results
After the eligibility criteria was met, the study included 13,527 apixaban and 2,914 LMWH treated patients with VTE and active cancer. Post IPTW, the treatment cohorts were balanced on baseline patient characteristics (Figure 1). In the follow-up period, the incidence rates (IR) per 100 person-years for recurrent VTE and MB were lower for apixaban than LMWH among patients with VTE and active cancer (Figure 2). Apixaban patients had a lower risk of recurrent VTE (HR: 0.42; 95% CI: 0.34–0.53) and MB (HR: 0.50; 95% CI: 0.41–0.61) when compared to LMWH (Figure 2).

Conclusion
In this observational cohort analysis of patients with VTE and active cancer, extended anticoagulation treatment of ≥3 months with apixaban was associated with a lower risk of recurrent VTE and MB compared with LMWH. Additional research is required to confirm these findings.Figure 1Figure 2
DNA methylation of ADAMTS7 gene promoter in direct oral anticoagulant-induced bleeding in patients with atrial fibrillation
Authors: Atzemian N , Ragia G , Thomopoulos T , Tsaliki V , Kolios G , Chalikias G , Trikas A , Tziakas D , Manolopoulos V G 
Published: November 2023

Abstract

Introduction
Direct Oral Anticoagulants (DOACs) are recommended as first-line treatment in atrial fibrillation (AF) patients. Despite their benefits and effectiveness, several patients experience bleeding events. No studies have addressed how epigenetic modifications may affect DOAC treatment. To fill this gap, we are conducting a study aiming to follow in time changes of DNA methylation patterns in naïve AF patients starting DOAC therapy. Herein, we present our findings regarding DNA methylation analysis of ADAM Metallopeptidase with Thrombospondin Type 1 Motif 7 (ADAMTS7), a protease that acts on the cardiovascular system.

Methods
A total of 76 AF patients treated with dabigatran, rivaroxaban, or apixaban and 22 non-AF controls were included. Genomic DNA has been isolated at baseline (t0, controls and patients), and for patients at 7 (t1) and 28 (t2) days of DOAC treatment. Blood genomic DNA was isolated and bisulfite converted prior to methylation analysis. Promoter DNA methylation of ADAMTS7 was analyzed with qMSP-PCR.

Results
In our study, no major bleeding or thrombotic events were recorded. A total of 16 minor bleeding events occurred. The percentage of ADAMTS7 methylation at baseline did not differ between patients and controls (16,8% vs. 14,8%, p=0,138). In patient cohort, DOAC therapy did not alter ADAMTS7 methylation at different timepoints (16,8% at t0, 15,7% at t1 and 14,3% at t2, p=0,293 from t0 to t1, p=0,06 from t0 to t2 and p=0,205 from t0 to t1). When patients were categorized into experiencing bleeding events (cases) or not (controls), ADAMTS7 was demethylated from t0 to t2 (-3,7% in cases vs. -1.2% in controls, p=0.015) and from t1 to t2 (-2,1% in cases vs. -1,1% in controls, p=0.034). In adjusted regression analysis, bleeding was associated with ADAMTS7 demethylation (β=-2,973, 95%CI -5,481, -0,466, p=0,021).

Conclusion
This is the first study of DNA methylation on DOACs. Our findings suggest that the methylation of the promoter of ADAMTS7 is reduced when DOAC-related bleeding occurs, increasing its expression levels, and may subsequently promote hemostasis and endothelium remodeling through different pathways.