bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implantable loop recorders in children and adolescents with Brugada syndrome: the YoungBruLoop study
Authors: Conte G , Ciconte G , Bergonti M , Crotti L , Tondo C , Rossi A , De Asmundis C , Caputo M L , Casella M , Saenen J , Pappone C , Schwartz P , Auricchio A , Brugada P , Sarquella Brugada G 
Published: October 2024

Abstract

Background
Young (&lt;18 years of age) patients with Brugada syndrome (BrS) are often underrepresented in BrS studies and their management, especially related to syncopal episodes, remains unclear.

Purpose
To describe the arrhythmia prevalence and clinical implication derived from continuous rhythm monitoring by implantable loop recorder (ILR) among patients younger than 18 years of age, and to assess the etiology behind syncope of undetermined origin.

Methods
A total of 147 BrS patients with ILR were enrolled in 12 international centers and divided into pediatric (age &lt;12 years; n=77, 52%) and adolescents (age 13 to 18 years; n=70, 48%).

Results
Mean age was 11.3 years (36.1% females, 21.1% spontaneous type I ECG). Forty-six patients (31.2%) underwent ILR implant due to syncope. Over a median follow-up of 3.6 years, an arrhythmic event was recorded in 22.4% of patients and in the vast majority of cases it was of non-ventricular origin (44% atrial, 47% bradyarrhythmias). Predictors of arrhythmias at univariate Cox Regression analysis were spontaneous type I ECG (HR 2.1 - 95%C.I. 1.1-4.1), history of syncope (HR 3.1 - 95%CI 1.5-6.3) and age &gt;12 years (HR 2.0 - 95%C.I. 1.0-3.3). Ventricular arrhythmias occurred in 4 patients, all with spontaneous BrS, and were related to fever in half of cases. In patients with recurrent syncope, the prevalence of truly arrhythmic syncope was 17.8%, and it was due to brady-, atrial- and ventricular arrhythmias in 40%, 20% and 40% of cases, respectively.

Conclusions
Continuous rhythm monitoring with ILRs in BrS pediatric patients detects a broad range of heart rhythm disturbances including life-threatening arrhythmias. Ventricular arrhythmias occur predominantly in patients with spontaneous type I ECG and in half of cases are fever-related. Despite the young age, brady- and atrial arrhythmias are overall frequent and represent the cause of arrhythmic syncope in 60% of patients. Young BrS patients with syncope of undetermined origin may benefit from ILR implant.
Impact of SGLT2 inhibitors on liver-related outcomes in patients with heart failure - a population-based study in HK
Authors: Yang H Y , Yang R Q , Yiu K H 
Published: October 2024

Abstract

Background
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are now recommended for heart failure with preserved ejection fraction (HFpEf). While their side effects on respiratory and renal outcomes in patients with type 2 diabetes have been studied, the impact on liver-related diseases within HF patients is not well-established.

Purpose
This study aims to evaluate the association between SGLT2 inhibitor use and the risks of adverse liver events among HF patients.

Methods
We conducted a retrospective cohort study using the Hong Kong Clinical Data Analysis and Reporting System (CDARS) to identify 80,248 HF patients (mean age 73.37 ± 12.88 years; 49.2% male) between 2013 and 2022. Propensity score matching was applied to achieve a 1:3 ratio of SGLT2 users to non-users, ensuring balanced baseline characteristics. Competing risk regression within Cox proportional hazards frameworks quantified the risks for cirrhosis, hepatocellular carcinoma, liver-related death, and significant elevations in liver enzymes (ALT or AST &gt;3x normal and bilirubin &gt;2x normal).

Results
During a median follow-up of 6.02 years (interquartile range: 3.48–9.25 years), there were 12,103 liver-related deaths. SGLT2 was associated with a 52% reduced risk of cirrhosis (adjusted subdistribution hazard ratio [SHR]: 0.48; 95% confidence interval [CI]: 0.36-0.65), a 61% lower risk of hepatocellular carcinoma (SHR: 0.39; 95% CI: 0.26-0.42), a 13% decreased risk of liver-related death (SHR: 0.87; 95% CI: 0.77-0.98), and a 19% risk reduction in elevated liver enzymes (SHR: 0.81; 95% CI: 0.68-0.96). 5-year cumulative incidences were 1.7%, 0.62%, 13%, and 5.4%, respectively, for SGLT2 users compared to 3.7%, 1.9%, 16%, and 7.0% for SGLT2 nonusers.

Conclusion
SGLT2 use is associated with a decreased risk of adverse liver outcomes in HF patients. This suggests a potential protective role for SGLT2 in liver health within this population.
The effect of oral anticoagulants on the incidence of dementia in patients with atrial fibrillation: a systematic review and meta-analysis
Authors: Latif F , Nasir M M , Meer K K , Farhan S H , Cheema H A , Khan A B , Umer M , Rehman W U , Ahmad A , Khan M A , Almas T , Mactaggart S , Nashwan A J , Ahmed R , Dani S S 
Published: October 2024

Abstract

Background
Atrial fibrillation (AF) is a common cardiac arrhythmia, with dementia being an increasingly recognised complication of this. Treatment with oral anticoagulant (OAC) therapy may be protective in developing this complication.

Purpose
This meta-analysis aims to investigate the validity of this hypothesis, whilst additionally exploring the effect of specific OAC medication subtypes on the incidence of dementia.

Methods
A comprehensive search of MEDLINE and Embase for relevant studies reporting the efficacy of OAC therapy for the incidence of dementia in patients with AF was conducted from its inception until March 2023. This included observational studies that reported odds ratio, risk ratio and hazard ratio for adult AF patients. Studies including patients with prior OAC use or prior history of dementia were excluded. Statistical analysis was performed using a random-effects model to calculate the pooled hazard ratio and their corresponding 95% confidence interval for all outcomes. Subgroup analyses were also performed according to the study design, presence of observational window, and prior history of stroke in patients.

Results
A total of 13 studies were included in the study. Although the heterogeneity was high in all comparisons, we demonstrated that OAC usage lowered the risk of developing dementia in AF patients when compared to the non-OAC cohort. Looking more specifically at medication subtypes, direct oral anticoagulants (DOACs) and vitamin K agonists (VKA) were both effective in reducing the likelihood of AF patients developing dementia when compared to non-OAC treatments.

Conclusion
Our meta-analysis confirms that administration of OAC and its subtypes (VKA and DOAC) are effective pharmacotherapies in managing dementia in patients with AF. These findings have important clinical implications for the management of AF patients and highlight the need for further investigation of the protective effects of OAC therapy on cognitive decline. Future research should explore the long-term effects of OAC therapy on cognitive function in AF patients.
Direct oral anticoagulants or warfarin in patients with left ventricular thrombus: a meta-analysis of randomized clinical trials
Authors: Maqsood M , Zhang R , Bangalore S 
Published: October 2024

Abstract

Background/Introduction
There are limited randomized controlled trials (RCTs) data on the use of direct oral anticoagulants (DOAC) versus warfarin in patients with left ventricular (LV) thrombus. Current AHA and ESC guidelines recommend oral anti-coagulants (either DOAC or warfarin) for 3 to 6 months without any preference.

Purpose
We aimed to compare outcomes with DOACs versus warfarin in patients with LV thrombus.

Methods
A comprehensive literature search was performed from inception to 02/01/2024 of the PubMed database. RCTs of adult patients comparing DOAC to warfarin were evaluated for mortality, major bleeding, stroke, and LV thrombus resolution. Meta-analytic Odds ratio (OR) with 95% confidence intervals (CI) were calculated using DerSimonian-Laird method.

Results
From 100 studies, four RCTs with 188 subjects (95 DOAC and 93 warfarin) were included with mean age of 53.4 years, 69.5% males, and mean follow up 5.03 months. There was no difference in mortality (OR= 0.67 [95% CI 0.15-3.06]; p=0.60; I2=0%; 3 trials), stroke (OR= 0.46 [95% CI 0.09-2.44]; p=0.37; I2=0%; 4 trials), major bleeding (OR= 0.43 [95% CI 0.12-1.55]; p=0.20; I2=0%; 4 trials), and LV thrombus resolution (OR= 1.33 [95% CI 0.45-3.95]; p=0.61; I2=0%; 2 trials) with use of DOAC compared to warfarin (Figure Panel A to D). Overall, there was no evidence of publication bias using either funnel plot or eggers test (p &gt; 0.05).

Conclusions
In this meta-analysis of 4 RCTs, there was similar efficacy and safety of DOAC and warfarin in patients with LV thrombus. However, the evidence is limited by small sample size with lesser precision in the estimates. Future large-scale trials are needed to confirm these findings.
Edoxaban for stroke prevention in routine practice patients with atrial fibrillation with and without atherosclerotic disease: a post-hoc sub-study of ETNA-AF-Europe
Authors: De Vries T A C , De Groot J R , Hemels M E W , Komen J J , Steffel J , Weiss T , De Asmundis C , Kirchhof P , De Caterina R 
Published: October 2024

Abstract

Background
Patients with atrial fibrillation (AF) and concomitant coronary and peripheral artery disease (CAD and/or PAD) have an increased risk of adverse health events compared to those without such atherosclerotic disease. The annual risks of major adverse cardiovascular outcomes for these patients treated with edoxaban in routine clinical practice remain uncertain.

Purpose
To determine the clinical characteristics and rates of key adverse events over multiple years of follow-up in patients with and without atherosclerotic disease (defined as CAD and/or PAD).

Methods
This is a post-hoc sub-study of ETNA-AF-Europe, a multinational, prospective cohort study on unselected patients with AF treated with edoxaban. In total, 13,164 (97%) of the 13,632 patients who provided informed consent were included in this substudy. The included patients were followed for a total of 48 months. Data were collected at baseline and yearly thereafter (±2 months). The present analysis compared baseline clinical characteristics (n [%] or mean [SD]) and clinical outcomes (events per 100 patient-years [%/year] with 95% confidence intervals [95% CI]) by CAD/PAD status at baseline.

Results
Of the 13,164 patients included in the analysis, 2973 had CAD and/or PAD (n=2762 CAD only). Patients with atherosclerotic disease were older (75.3 years vs 73.2 years), had higher CHA2DS2-VASc scores (3.8 vs 3.0) and HAS-BLED scores (2.8 vs 2.4), and more frequently received the reduced dose of 30 mg edoxaban than those without CAD/PAD (30.2% vs 21.0%) (Table). Cardiovascular comorbidities were in general more prevalent in those with atherosclerotic disease vs those without.
Rates of stroke or systemic embolism (0.89%/year, 95%-CI 0.72–1.09 vs 0.59%/year, 95%-CI 0.52–0.68), myocardial infarction (0.73%/year, 95%-CI 0.58–0.92 vs 0.25%/year, 95%-CI 0.20–0.30), and cardiovascular (1.56%/year, 95%-CI 1.33–1.83 vs 0.85%/year, 95%-CI 0.76–0.95) as well as all-cause death (5.96%/year, 95%-CI 5.50–6.46 vs 3.56%/year, 95%-CI 3.37–3.77) were higher for patients with CAD/PAD vs those without such atherosclerotic disease (Figure).

Conclusion
Annual rates of thromboembolic and bleeding events were low for AF patients treated with edoxaban in routine practice. The higher rates of thrombotic and bleeding events in patients with CAD/PAD are most likely caused by differences in baseline intrinsic risks. Nonetheless, these differences, particularly the threefold higher rate of myocardial infarction, warrants further investigation.Baseline Characteristics
Characterisation of the pharmacokinetic and pharmacodynamic relationship of milvexian in total knee replacement patients
Authors: Zhou W , Bozenhardt E , Merali S , Zannikos P , Back H , Ajavon-Hartmann A , Strony J , Plotnikov A , Chintala M , Goyal N , Samtani M 
Published: October 2024

Abstract

Background
Milvexian, an oral factor XIa inhibitor, is currently being evaluated in patients at risk for thrombotic events due to atrial fibrillation, ischaemic stroke, or acute coronary syndrome. The exposure-response relationship between clinical efficacy and safety endpoints and milvexian pharmacokinetic (PK) metrics was recently submitted as a separate publication. Characterisation of the relationship between the coagulation pharmacodynamic (PD) markers versus milvexian PK metrics at the patient level has yet to be reported.

Purpose
This analysis characterised the relationship between the coagulation biomarkers, activated partial thromboplastin time (aPTT) and prothrombin time (PT), and milvexian systemic exposure in patients undergoing total knee replacement (TKR) evaluated in the AXIOMATIC-TKR study.

Methods
A population pharmacokinetic (PopPK) model was previously developed and characterised the PK of milvexian in TKR patients well. The PK/PD relationships between observed aPTT and PT versus PopPK model estimated time-matched milvexian plasma concentrations via nonlinear mixed effects modeling. The relationship between key clinical safety endpoints (e.g., any bleeding or clinically relevant non-major bleeding) and individual PD marker change (e.g., aPTT ratio to baseline) was also explored.

Results
The aPTT increased with increasing plasma concentration of milvexian over the range of doses evaluated in the study (25mg QD to 200mg BID). An Emax type of model reasonably characterised the PK/PD relationship between the aPTT and model predicted time-matched milvexian plasma concentration, which is consistent with previously observed relationships in healthy volunteers. No change was observed in PT with increased milvexian exposure. No obvious relationship was identified between any (including clinically relevant non-major) bleeding and aPTT ratio to baseline.

Conclusions
Increased milvexian exposure is directly correlated with aPTT prolongation over the range of doses evaluated in the TKR study. There was no obvious relationship between any (including clinically relevant non-major) bleeding and aPTT ratio. The PK/PD relationship of aPTT without a parallel relationship in PT distinguishes milvexian, a FXIa inhibitor, from previously studied FXa inhibitors. These analyses were a complementary component in dose selection for the milvexian Phase 3 program.
Figure 1. PK/PD relationship between aPTT (left) and PT (right) and estimated time-matched plasma concentration (AXIOMATIC-TKR study)
Comparative effects of different antiplatelet strategies in carriers of CYP2C19 loss-of-function alleles: a network meta-analysis
Authors: Galli M , Occhipinti G , Benenati S , Laborante R , Ortega-Paz L , Franchi F , D'amario D , Frati G , Biondi-Zoccai G , Sciarretta S , Angiolillo D J 
Published: October 2024

Abstract

Background
Carriers of cytochrome 2C19 (CYP2C19) loss of function (LoF) alleles treated with clopidogrel have impaired drug metabolism resulting in reduced active metabolite levels, high platelet reactivity (HPR), and an increased risk of thrombotic events. Several alternative antiplatelet therapies have been proposed to overcome HPR in these patients, but their comparative effects remain poorly explored.

Purpose
To assess the comparative effects of different alternative antiplatelet agents in carriers of CYP2C19 LoF alleles undergoing percutaneous coronary interventions (PCI).

Methods
Randomized controlled trials (RCTs) comparing different oral antiplatelet therapies in carriers of CYP2C19 LoF alleles undergoing PCI were included. A frequentist network meta-analysis was conducted to estimate mean difference (MD) or odds ratios (OR) and 95% confidence intervals (CI). The primary outcome was platelet reactivity assessed by VerifyNow and reported as P2Y12 reaction unit (PRU). The secondary outcome was the rate of HPR as defined in each trial. Standard-dose of clopidogrel (75 mg daily) was used as reference treatment. Antiplatelet strategies were ranked according to P-scores, ranging between 0 (poor performance) and 1 (good performance).

Results
A total of 13 RCTs testing 6 alternative strategies (i.e., clopidogrel 150 mg, prasugrel 3.75 mg, 5 mg, and 10 mg, ticagrelor 90 mg bid, and adjunctive cilostazol 100 mg bid) were included in the network. Compared with standard-dose clopidogrel, the greatest reduction in PRU was observed with prasugrel 10 mg (MD -128.61; 95% CI -145.09; -111.49) and ticagrelor 90 mg bid (MD -125.61; 95% CI -170.66; -80.56), followed by prasugrel 5 mg (MD -118.03; 95% CI -143.15; -92.92) and prasugrel 3.75 mg (MD -73.00; 95% CI -108.97; -37.03). High-dose clopidogrel was associated with a modest (MD -32.11; 95% CI -51.33; -12.90) and adjunctive cilostazol with a non-significant (MD -44.11; 95% CI -98.05; -9.82) reduction in PRU compared with standard-dose clopidogrel (Figure 1). Rates of HPR were reduced with all treatments compared with standard-dose clopidogrel. Ranking of treatments for the primary endpoint showed that standard-dose prasugrel ranked as the best treatment (P-score=0.884), followed by ticagrelor (P-score=0.835), low-dose prasugrel (0.767), very-low dose prasugrel (P-score=0.474), cilostazol (P-score=0.306), high-dose clopidogrel (P-score=0.224), and standard-dose clopidogrel (P-score=0.009) (Figure 2).

Conclusion
Among carriers of CYP2C19 LoF alleles undergoing PCI, standard-dose prasugrel or ticagrelor are most effective in reducing platelet reactivity, followed by reduced-dose of prasugrel, while double-dose clopidogrel and adjunctive cilostazol showed only modest effects. The clinical implications of these pharmacodynamically effective strategies warrant further investigation.
A novel formula to assess the QT interval in ventricular paced rhythm
Authors: Almasri A , Werner C , Gieres C , Ukena C , Boehm M , Abdin A 
Published: October 2024

Abstract

Background
QT interval measurement in the presence of right ventricular pacing (RVP) represents a clinical challenge due to altered ventricular activation resulting in a prolonged QT-interval. The aim of this study is to compare the QT interval in patients before and after ventricular pacing to develop a new formula for QT interval assessment in patients with RVP.

Methods and results
All patients presenting to our pacemaker clinic with single- or dual chamber device were included in this prospective observational study. Inclusion criteria were no permanent right ventricular stimulation, an intrinsic QRS interval of &lt;120 ms, and ventricular rate &gt;35 bpm and &lt;150 bpm. Three 12-lead electrocardiograms were recorded for each patient: during intrinsic rhythm and 2 following an atrial paced and a ventricular paced QRS at the same rate. The intrinsic QRS and QT time/JT time (QTi/JTi) were measured during intrinsic and subsequent RVP. To obtain the formula, all measurements were performed on 100 patients (mean age 74 ± 11.3, male 33%) (RV apical lead 30% and non-apical lead 70%). Based on our measurements, a new formula QT (non-paced) = 139.23 + 0.55 xQT (paced) was derived. A population of 482 individuals (mean age 75.5±13.2 years (SD), 64% male) with permanent RV pacing were used as a validation group. The intrinsic QRS and QT time were measured during SR and subsequent RVP. To assess the relationship between the predicted QT with RVP and the measured QT without RVP, linear correlations analyses were performed. Our formula had a strong correlation with the irrespective QT without RVP (r=0.50)

Conclusion
We proposed a new simple formula to accurately estimate QT during RVP. This formula can be easily utilized in clinical practice.
Figure 1: MAD characteristic value via plots stands for Median Absolute Difference (i.e. by how many ms the prediction is estimated on average).
Figure 2: "Forest Plot" illustrates the correlation coefficients in the form of a forest plot. The dot r represents r and the bars the 95% confidence intervalsMAD characteristic value via plots standForest Plot" illustrates the correlation
Pretreatment with dual antiplatelet therapy in acute myocardial infarction
Authors: Motovska Z , Hlinomaz 0 , Kala P , Benesova K , Mrozek J , Hromadka M , Muzafarova T , Precek J , Matejka J , Tomasov P , Bis J , Cervinka P , Vodzinska A , Hrabos V , Jarkovsky J 
Published: October 2024

Abstract

Background
Combined antithrombotic therapy prevents thrombus progression and its components embolization, and thus, it has an essential role in coronary microcirculation (re)perfusion in acute myocardial infarction (AMI). Pretreatment with P2Y12 inhibitors, on top of aspirin, before primary angioplasty has not been satisfactorily studied in STEMI.

Purpose
To investigate the impact of combined antiplatelet therapy on-treatment on the outcome of patients with STEMI.

Methods
Patients who suffered STEMI during the 7 years (1/2016-12/2022) were included. The analysis is based on population data from the National Health Information System (NHIS). Information on AMIs from the Intervention Module of the Registry of Cardiovascular Operations and Interventions was combined with prescription data from the Registry of Reimbursed Health Services 6 months before MI and identification of deceased patients from the Registry of Death Records. Data from the NHIS covers almost 100% of all cases in the population. Standard descriptive statistics and test were applied in the analysis. Multivariate logistic regression adjusted for clinical and procedural characteristics was adopted to analyze the influence of pretreatment on the risk of 1) out-of-hospital cardiac arrest (OHCA), 2) clinical condition at admission – need of mechanical ventilation and circulatory instability (Killip III,IV), 3) initial TIMI flow through the infarct-related coronary artery (IRA ), and 4) short term mortality.

Results
The study sample consisted of data from 40,383 STEMIs of which 1,601 patients were on dual antiplatelet therapy (DAPT) with aspirin plus iP2Y12 lasting 1 to 6 months before the event occurred. Patients on chronic oral anticoagulation (N 2101) were excluded. Patients on DAPT versus those without antiplatelet therapy or on aspirin at a daily dose of 100 mg were older, had higher comorbidity rates, and were at higher risk of mortality (Table).
The multivariate logistic regression analysis showed that patients on DAPT at the time of MI onset and lasting for at least one month had a higher likelihood of preserved perfusion through the IRA (Odds ratio and 95% Confidence interval, OR (95% CI) 1. 193 (1.074; 1.326), p=0.001). However, the DAPT pretreatment did not reduce the risk of OHCA, the need for mechanical ventilation, or initial circulatory destabilization. It did not positively affect the prognosis of the patients (Figure ).

Conclusion
The significant benefit of the DAPT pretreatment on the preservation of infarct-related coronary artery flow did not translate into a positive effect on the prognosis of STEMI patients.