bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implications of renal function on adverse clinical events in patients with atrial fibrillation: a comparative analysis of VKA and NOAC therapy - Insights from the GLORIA-AF Registry Phase III
Authors: Liu Y , Chen Y , Lam S H M , Huang B , Chao T F , Olshansky B , Lip G Y H 
Published: October 2024

Abstract

Background
Renal function, as assessed by creatinine clearance (CrCl), plays a crucial role in determining the efficacy and safety of oral anticoagulant (OAC) therapy in patients with atrial fibrillation (AF).

Purpose
To investigate the relationships between CrCl and the risk of clinical adverse events in patients with AF receiving OAC therapy, comparing the safety profiles of vitamin K antagonists (VKA) and non-vitamin K antagonist oral anticoagulants (NOACs).

Methods
Anticoagulated AF patients from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry Phase III were studied. CrCl was calculated for renal function, according to Cockcroft-Gault equation. Restricted cubic spline (RCS) were used to explore the nonlinear association between adverse end events and CrCl, comparing VKA and NOAC therapy. Cox regression models were used to analysis the associations between adverse end events and OAC therapy in patients with different CrCl levels, adjusted by clinical features and previous disease. Patients were followed up for the composite outcome (all-cause death, thromboembolism and major bleeding), all-cause death, cardiovascular disease (CVD), major bleeding, myocardial infarction (MI) and stroke.

Results
In 10,594 AF patients (mean age 70.35 ± 9.92 years; 55% male; 73% on NOAC), RCS analysis revealed decreased risks of all cause death, composite outcomes and CVD with increasing CrCl in patients with CrCl &lt; 80 mL/min.
Multivariate Cox models indicated that NOAC therapy associated with lower risk of all cause death (HR 0.68, 95% CI 0.58-0.78), composite outcomes (HR 0.77, 95% CI 0.68-0.86), CVD (HR 0.7, 95% CI 0.56-0.87), major bleeding (HR 0.74, 95% CI 0.61-0.91) in AF patients. For CrCl &gt; 95 mL/min, a lower risk of all cause death (HR 0.56, 95% CI 0.38-0.82), composite outcomes (HR 0.68, 95% CI 0.51-0.91) and major bleeding (HR 0.54, 95% CI 0.35-0.85) were associated with NOAC therapy, vs. VKA.
For CrCl &lt; 30 mL/min, a lower risk of all cause death (HR 0.47, 95% CI 0.28-0.81), composite outcomes (HR 0.56, 95% CI 0.35-0.89) and CVD (HR 0.43, 95% CI 0.20-0.90) were related to NOAC therapy. No significant difference in outcomes between VKA and NOAC were found in patients with moderate CrCl.

Conclusion
Increasing CrCl were associated with decreased risk of adverse clinical events, including all-cause death and CVD in anticoagulated AF patients. For patients with CrCl &gt;= 95 and &lt; 30, NOAC therapy, was associated with lower risks of adverse outcomes.Figure 1Figure 2
Switching from warfarin to a DOAC in frail elderly asian patients with atrial fibrillation: a nationwide population-based study
Authors: Go Y , Lee S , Choi E , Rha H , Jeong M , Yeo M , Choi J , Lee K , Ahn H , Kwon S , Kim B , Han K , Oh S , Lip G 
Published: October 2024

Abstract

Background
Recently, switching international normalized ratio guided warfarin management to a direct oral anticoagulant (DOAC) was associated with more bleeding complications than maintaining warfarin in frail elderly patients with atrial fibrillation (AF). However, there is a paucity of information on whether these results could be applied to Asian patients with AF, who are known to have relatively low time in therapeutic range (TTR) levels.

Purpose
To evaluate the safety and effectiveness of switching from warfarin to a DOAC in frail elderly Asian patients with AF.

Methods
Using a Korean health insurance database, we included patients with AF who were prescribed warfarin between January 2013 and August 2015 without significant bleeding or thromboembolic events during the window period, specifically those aged 75 or older with a Hospital Frailty Risk Score of 5 or more. Those who switched to DOACs during the window period were categorized as the DOAC group and those who continued with warfarin were categorized as the warfarin group. The primary outcome was defined as the composite of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB), and secondary outcomes were defined as thromboembolic events, all-cause death, the composite of MB, CRNMB and ischemic stroke (so-called net clinical outcome [NCO]). The propensity score weighting method was utilized to compare the two groups.

Results
A total of 12,162 patients were included (8,108 with maintaining warfarin, 4,054 with switching to a DOAC). Baseline characteristics were well-balanced after the inverse probability of treatment weighting (mean age, 80 years; men, 50%; and mean CHA₂DS₂-VASc score, 5.6). Compared with maintaining warfarin, switching to a DOAC was associated with significantly higher risks of the primary outcome (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.09-1.87, p=0.01), thromboembolic events (1.28, 1.01-1.62, p=0.039), all-cause death (1.38, 1.15-1.66, p&lt;0.001) and the NCO (1.26, 1.01-1.58, p=0.04). (Figure A, Figure B), whereas there was no difference in the risk of intracerebral hemorrhage (0.90, 0.50-1.60, p=0.7157). When comparing each DOAC with maintaining warfarin, switching to rivaroxaban was associated with a higher risk of the composite of MB and CRNMB (1.91, 1.38-2.64, p&lt;0.001) and thromboembolic events (1.40, 1.03-1.91, p=0.034) than maintaining warfarin.

Conclusion
In line with the non-Asian population, switching to a DOAC was associated with a significantly higher risk of MB or CRNMB, thromboembolic events, all-cause death and NCO compared with maintaining warfarin in frail elderly Asian patients with AF. Therefore, even in Asians, switching to a DOAC should be considered more cautiously in patients who are stably managed on warfarin.
Plasma apixaban levels and thrombin generation assay in patients with atrial fibrillation with dose reduction criteria of apixaban
Authors: Yeo M , Lee S R , Choi E K , Ahn H J , Kwon S , Oh S 
Published: October 2024

Abstract

Background
Off-label reduced-dose apixaban is commonly prescribed in patients with atrial fibrillation (AF). However, the pharmacokinetic data of apixaban according to the dosage and label is limited especially in those with dose reduction criteria of apixaban.

Purpose
We investigated the apixaban plasma concentration (PC) and thrombin generation assay (TGA) parameters across different apixaban dose settings.

Methods
We enrolled 398 non-valvular AF patients with more than single-dose reduction criteria of apixaban and divided them into three groups: (1) on-label standard dose (single dose-reduction criterion with standard-dose of apixaban 5mg twice daily, n=173); (2) off-label reduced-dose (single dose-reduction criterion with apixaban 2.5mg twice daily, n=61); and (3) on-label reduced-dose (two or more dose-reduction criteria with apixaban 2.5mg twice daily, n=164). Apixaban PC by anti-Xa assay and TGA parameters of these three groups were compared at the trough level.

Results
The on-label standard dose group showed a higher PC than the on-label reduced dose (124.7 vs. 80.3 ng/mL, p&lt;0.001), and the on-label reduced dose exhibited a higher PC than the off-label reduced dose (80.3 vs. 53.2 ng/mL, p=0.031) (Figure). The TGA parameters displayed a similar pattern of differences, with the on-label standard dose group tends to show the least thrombogenic profiles (Figure). Lower creatinine clearance (CrCl), older age, and female sex were statistically significant predictors for a higher apixaban PC by multivariable regression model (p&lt;0.001, p=0.043, and 0.023, respectively), and CrCl was the most influential variable to dichotomize apixaban PC in all three groups (Figure).

Conclusions
Off-label reduced-dose apixaban group exhibited significantly lower apixaban level than both on-label standard dose and on-label reduced-dose apixaban groups, suggesting the importance of adhering to current dose-reduction criteria for maintaining appropriate apixaban levels. Caution is particularly advised in off-label under-dosing for patients with high creatinine clearance. Further investigation into the impact of off-label under-dosing on clinical outcomes is essential to guide optimal therapeutic strategies.
Prognostic value of left atrial strain for outcome of catheter ablation in patients with atrial fibrillation and moderately enlarged left atrium
Authors: Kim M H , Cho I , Kim K , Kim D , Yu H T , Kim T H , Joung B , Lee M H , Pak H N 
Published: October 2024

Abstract

Background
Atrial fibrillation catheter ablation (AFCA) is an effective rhythm control method for patients with AF, but AF recurrence is higher in patients with a large left atrium (LA). We explored whether pre-procedural LA strain has incremental prognostic value for the long-term rhythm outcomes of AFCA in patients with AF and moderately enlarged LA size (45≤LA diameter&lt;50mm).

Methods
We included 2,269 patients who underwent de novo AF catheter ablation (men 72.2%, 59.1[±10.7] years, paroxysmal AF 64.0%). We divided grouped into 5 mm increments and determined the appropriate cut-off of LA diameter (45mm) predicting the difference in long-term rhythm outcome by the log-likelihood values of multivariate Cox proportional hazard models. Patients with moderately enlarged LA size (45≤LA diameter&lt;50mm, n=413) with borderline rhythm outcomes were used for analysis.

Results
In the cohort of 413 patients who underwent AFCA with moderately enlarged LA size, AF was recurred in 208 patients (43.7%) after AFCA. We determined the appropriate cut-off of LA strain (12.5) predicting the difference in long-term rhythm outcome by the log-likelihood values of multivariate Cox proportional hazard models. During 24 months [10-50] follow-up, patients with low LA strain (&lt;12.5) were showed worsen rhythm outcome than high LA strain (Log-rank p&lt;0.001). Patients with AF recurrence after AFCA were independently associated with low LA strain (HR 1.539 [1.130-2.094], p=0.006), and paroxysmal AF (OR 0.651 [0.469-0.905], p=0.011). Furthermore, the likelihood ratio test demonstrated a significant influence of adding LA strain by TTE (χ2 = 13.90 [P &lt; 0.001]).

Conclusions
LA strain using baseline echocardiography has a predictive power for AF recurrence after AFCA in patients with moderately enlarged LA size (45≤LA diameter&lt;50mm).
Impact of changes in proteinuria on the risk of atrial fibrillation in patients with diabetes mellitus: a nationwide population-based study
Authors: Rha H , Lee S R , Choi E K , Go Y H , Jeong M H , Choi J M , Lee K Y , Kwon S , Kim B , Han K D , Oh S , Lip G 
Published: October 2024

Abstract

Background
Diabetes mellitus (DM) is a well-known risk factor for atrial fibrillation (AF). Proteinuria is also considered as an independent predictor for AF. However, there is limited data on whether the changes in proteinuria severity can impact the risk of AF among patients with DM.

Purpose
We aimed to evaluate the association between changes in proteinuria over time detected using a urine dipstick test and the risk of AF among patients with DM.

Methods
A total of 1,605,495 patients with DM who underwent two biennial health checkups provided by the National Health Insurance Service (NHIS) between January 2013 and December 2016 were included. All patients had two consecutive urine dipstick tests during the checkups. We divided the study population into four groups based on their glomerular filtration rate (GFR): &gt; 90 ml/min, 60-90 ml/min, &lt; 60 ml/min, and those with end-stage renal disease (ESRD). We evaluated the association between the changes in proteinuria over time detected using a urine dipstick test and the risk of AF and their changes by GFR.

Results
During a median 4.0-year follow-up, AF occurred in 32,391 persons (5.22 per 1,000 person-years). Among 1,605,495 patients who underwent two consecutive urine dipstick tests, 1,453,116 (90.51%) patients had a negative proteinuria on both tests (negative or trace result on both urine dipstick tests), and 68,979 (4.3%) patients had an aggravated proteinuria (from negative to more than 1+ result on subsequent urine dipstick test). While 48,357 (3.01%) patients had a resolved proteinuria (from positive to negative results on subsequent tests) and 35,043 (2.18%) patients had a persistent proteinuria (positive result on both tests). Those with aggravated or resolved or persistent proteinuria showed an increased risk of AF (HR 1.39, 95% CI 1.33-1.46; HR 1.37, 95% CI 1.30-1.45; HR 1.95, 95% CI 1.85-2.06) compared with most subjects who showed subsequent negative results on proteinuria. This result was consistent within every GFR group. However, the tendency of increment of AF risk by changes in proteinuria was more prominent in lower GFR groups (Table). In subgroup analysis, there was no significant difference between male and female. However, the younger aged (&lt; 65 years) group had a more prominent tendency of increased AF risk by changes in proteinuria.

Conclusion
Changes in proteinuria showed a significant association with the risk of AF in patients with DM. This tendency was prominent in patients with lower GFR. Therefore, careful monitoring of AF risk based on proteinuria changes could be beneficial for those with DM.
Automatic measurement of stimulation to maximum negative dv/dt in V5 and V6 leads to confirm left bundle capture for conduction system pacing
Authors: Musat D , Bhatt A , Paamand R , Leonard O , Firth K , Mittal S 
Published: October 2024

Abstract

Introduction
Left bundle area conduction system pacing is obtained when the ventricular pacing lead is implanted into the right ventricular septum and captures the left bundle branch, demonstrated by right bundle branch morphology in the lead V1 and short stimulation to R-wave peak time (SRWPT) in leads V5 or V6. Manual measurements are challenging and result in significant variability. Maximum negative dv/dt in leads V5 and V6, occurring immediate after maximal lateral wall depolarization, represents the ideal measurement of synchronicity of left ventricular depolarization, as suggested by the guidelines.

Objective
To test feasibility of automatic algorithm to measure the maximum negative dV/dt in comparison to manual SRWPT measurement in V5 and V6.

Method
Data was collected from 7 patients with confirmed left bundle branch capture. Three trained operators manually measured SRWPT in leads V5 and V6 (Figure A). An algorithm capable of automatically measuring stimulation to maximum dv/dt was retrospectively applied to the same measured beats. Variability and correlation of measurements was compared between manual and automatic using the Bartlett Test for equal variance.

Results
In total, 137 individual beats were measured in the 2 leads by three operators resulting in 822 manual measurements. The mean variability of SRWPT in V5 and V6 was 2.9 ± 0.7 msec and 3.1 ± 1.1 msec, respectively (inter-operator correlation of 0.83). In contrast the stimulation to max negative dv/ dt mean variability in V5 and V6 was 1.3 ± 0.4 msec and 1.2 ± 0.5 msec, respectively (P &lt; 0.001). The comparison of variation in measurement between manual and automatic measures are shown in a box and whisker plot in figure 2.

Conclusion
Manual measurement of SRWPT can be challenging resulting in higher variability compared to an automatic algorithm measuring max negative dv/dt. This study demonstrates the feasibility of automatic interval measurement in conduction system pacing; however, further studies are required to validate the reliability of such tool.Fig 1.Example ECG interval measurement
High incidence of malignant arrhythmias and heart failure in patients with RBM20-associated cardiomyopathy: a multicenter cohort study and review of the literature
Authors: Tukker M , Te Rijdt W , Amin A S , Morris-Rosendahl D J , Hirsch A , Ben-Haim Y , Houweling A C , Varnava A , Behr E R , Hajdarpasic A , Von Der Thusen J , Michels M , De Boer R A , Van Slegtenhorst M A , Caliskan K 
Published: October 2024

Abstract

Background
Patients with RBM20 cardiomyopathy commonly experience malignant arrhythmias, sudden cardiac death (SCD), and progressive heart failure (HF).

Objective
The aim of this study is to investigate genotype-phenotype correlations, clinical outcomes and causes of death in patients with RBM20-associated cardiomyopathy in a multicenter cohort, combined with an overview of the current literature.

Methods
This international, multicenter cohort included all patients with cardiomyopathy who had a pathogenic (P) or likely pathogenic (LP) RBM20 variant. For survival and regression analysis, we matched a control group based on sex, age, and presence of left ventricular dysfunction. Additionally, we conducted a literature search on studies investigating RBM20-associated cardiomyopathy.

Results
Sixty-two patients (45% male) were included in the study, with a mean age of 42 ± 15 years at presentation. Of the LP/P RBM20 variants identified, 9 were novel. Eleven variants were truncating, while the remaining variants consisted of missense and splice-site variants. Patients with a truncating variant who developed HF were on average older at the time of diagnosis compared to patients with missense variants (mean age 62 ± 9 vs. 45 ± 14; p=0.01). After a median follow-up duration of 5.0 [1.0 – 10.5] years, 21 (34%) patients reached the composite endpoint of ventricular arrhythmias (VA), implantable cardioverter-defibrillator therapy, heart transplantation (HTx), left ventricular assist device (LVAD) implantation, or cardiovascular death. Of these, 19 (31%) patients experienced malignant VA (mean age 45 ± 15 years, 63% males). Males were at higher risk for the composite endpoint (log-rank p= 0.02), particularly for VA (log-rank p=0.007). The literature review analyzed 34 studies with a total of 678 patients, of whom 53% were male. In these studies, 123 (24%) patients experienced a VA, 58 (12%) underwent HTx or were treated with LVAD, and 52 (11%) died.

Conclusion
In this multicenter study the patients carrying a LP/P variant in RBM20 variants had a severe phenotype, with a high incidence of VA, particularly in males. Additionally, this study presents 9 novel DNA variants, of which 8 were truncating, and were mainly observed in older individuals. Finally, we report a lower mortality rate compared to the literature, possibly due to a higher number of heart transplantations performed in our patient cohort.Survival composite endpoint for sex
Refining risk stratification in hypertrophic cardiomyopathy: the role of late gadolinium enhancement and syncope in predicting adverse outcomes
Authors: Mann C , Dachs T M , Tosun R , Kronberger C , Beitzke D , Loewe C , Kammerlander A A , Hengstenberg C , Zelniker T A , Dalos D 
Published: October 2024

Abstract

Background
The presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (MRI) is recognized as a significant marker of myocardial fibrosis and a predictor of adverse outcomes in hypertrophic cardiomyopathy (HCM). Nevertheless, the specific quantity of LGE that correlates with poor outcomes is still under debate. Therefore, this study sought to assess the combined impact of LGE presence and a history of syncopal events and its association with clinical prognosis.

Methods
Between May 2018 and June 2023, a total of 230 HCM patients was prospectively enrolled at our Medical University, a tertiary referral center. The primary endpoint was a composite of new-onset ventricular tachycardia (VT), appropriate ICD therapy, and all-cause mortality.

Results
Median age of enrolled patients was 56 (IQR 44-64) years and 40% (n=94) were female. Median interventricular septal thickness (IVS) was 21 (IQR 18–25) mm and 43 % (n=84) had significant left ventricular outflow tract obstruction (LVOTO).
Over a median follow-up of 3.2 years, 30 patients (13%) met the composite endpoint. These patients had a significantly higher LGE quantity compared to the non-event group (1.1 % vs. % 9.0, P=0.012). An LGE threshold of 5.2% was identified as an optimal predictor of the composite endpoint, with an area under the curve of 0.72, which increased to 0.77 when including at least one syncopal event in medical history. LGE &gt; 5.2% and/or syncope were independently associated with adverse outcomes after multivariable adjustment (Adj HR 7.26 [95%CI 2.54-20.72]).
Furthermore, NTproBNP and hsTnT were associated with the presence of LGE or syncope (OR for a 1-unit increase in standardized log-transformed biomarker NTproBNP 3.35 [95%CI 1.42-10.85]; hsTnT 3.48 [95%CI 1.48-10.24], respectively). Interestingly, typically used variables for risk stratification, such as age, IVS or LVOT were not significantly associated with these cardiac biomarkers.

Conclusion
An extent of LGE &gt; 5.2% and the history of at least one syncope are associated with unfavorable clinical outcomes in HCM patients. These findings call for detailed MRI appraisal and suggest adopting a holistic approach to accurately identify high-risk patients.
The association between exercise-induced ventricular premature contractions and long-term mortality in patients without coronary artery disease
Authors: Pay L , Tezen O T , Cetin T C , Eren S E , Oz M O , Coskun C C , Yumurtas A C Y , Karabacak C K , Yeniturk B Y , Cinar T C , Hayiroglu M I H 
Published: October 2024

Abstract

Background/Introduction
The treadmill exercise test is widely used clinical test to determine cardiovascular risk and mortality, regardless of clinical risk factors (1). ST-segment changes detected in the exercise test are shown to predict myocardial ischemia (2) and premature ventricular complexes (PVCs) are frequently observed during exercise stress testing (3). Exercise-related PVC is observed in 14% to 23% of healthy individuals without significant heart disease (4,5). The literature on the role of PVCs observed during treadmill exercise testing in predicting prognosis is controversial.

Purpose
Therefore, we aimed to evaluate the clinical results of PVCs seen during exercise testing in patients who had been diagnosed with non-obstructive coronary artery disease after coronary angiography.

Methods
The study population consisted of 1624 consecutive patients who were considered high risk according to the Duke treadmill risk score and had no significant stenosis on coronary angiogram from January 2016 to April 2021. Patients with previous history of coronary revascularization, previous myocardial infraction, heart failure, moderate or severe heart valve disease, congenital heart disease, cardiomyopathy, bundle branch block, and left ventricular hypertrophy were excluded from the study. The primary endpoints of the study were long-term all-cause mortality of patients who had PVCs during the exercise test or during the resting phase.

Results
The long-term mortality was observed in 53 patients out of 1624 patients in the mean follow-up of 47 months. PVCs was observed in 293 (18.7%) patients without long-term mortality, while PVCs was observed in 24 (45.3%) patients with long-term mortality (p&lt;0.001). The model adjusted for all covariates showed that the presence of PVCs in the recovery phase (p&lt;0.007, HR (95% CI) 2.244 (1.244 – 4.047)) and advanced age (p&lt;0.001, HR (95% CI) 1.194 (1.143 – 1.247)) were associated with long-term all-cause mortality (Figure 1). Considering Kaplan-Meier curve, individuals with PVCs in recovery had significantly higher risk of long-term mortality compared with those with without PVCs (log-rank statistic: 22.47, p&lt;0.001) (Figure 2).

Conclusion(s)
The study highlights that PVCs monitored in the recovery phase of the treadmill exercise test were associated with long -term mortality in patients without structural heart disease and coronary artery disease.Figure 2Figure 1