bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune modulating drugs and oral anticoagulation in kidney transplant recipients: comparison of direct oral anticoagulants versus antagonist of vitamin-k. results from a multicenter prospective study
Authors: Santoro F , Casanova A , Simone S , Pellegrino P L , D'arienzo G , Brunetti N D , Pesce F 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
direct oral anticoagulants (DOACs) are a well-known alternative to conventional antagonist of vitamin-K (avK) and have emerged as the preferred choice due to their safety and efficacy profile. However, immune modulating drugs as cyclosporine and tacrolimus, commonly used for transplant recipients, may interfere with DOACs.
Aim of this study: evaluate safety and efficacy profile of direct oral anticoagulants (DOACs) compared to warfarin in kidney transplant recipients (KTRs) treated with immune modulating agents.

Methods
a multi-center study from 4 Italian hospitals enrolling KTRs on DOACs or avK was carried out. Sixty-nine patients on DOACs were compared with fifty patients on avK with mean estimated glomerular filtrate rate (eGFR) &gt; 45 mL/min. Clinical follow-up and serial evaluation of renal function and serum levels of immune modulating drugs during 24 months follow-up (FU) was performed.

Results
Mean age of DOACs patients was 67±9 and mean eGFR was57±20 mL/min. Immune-modulating therapy included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). There were no changes in Tacrolimus and Cyclosporin serum levels following 14 days therapy with DOACs (+0.5 ±2 and +28 ±31, p=0.52, 0.90, respectively) and only a patient treated with dabigatran 150 mg required a dose adjustment. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during follow-up.
At long-term follow-up, there were no thromboembolic events among patients treated with DOACs or avK and no differences in term of mayor bleeding (5.8% vs 4% p=0.99). There was no difference in term of eGFR decline from start therapy to 24 months FU between DOACs or avK therapy (-3.9±1 vs -3.8±2 p=0.82) (FIGURE 1).

Conclusion
DOACs are a potential therapeutic option among patients with kidney transplant recipients treated with immune modulating drugs. Careful evaluation of immunomodulating agent levels during the first two week of therapy should be recommended. No difference in term of bleeding, renal function decline was found when comparing with avK therapy.
Prognostic value of chronic kidney disease in patients undergoing left atrial appendage occlusion
Authors: Della Rocca D , Magnocavallo M , Van Niekerk C , Gilhofer T , Ha G , D'ambrosio G , Galvin J , Urbanek L , Schmidt B , Geller J C , Mansour M , Saw J , Horton R P , Gibson D , Natale A 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist and share an increased risk of thromboembolic events. CKD concomitantly contributes to several pathophysiological changes predisposing towards a pro-haemorrhagic state.

Purpose
To evaluate the impact of kidney function on peri-procedural complications and clinical outcomes in AF patients undergoing left atrial appendage occlusion (LAAO) with a Watchman device.

Methods
2124 consecutive AF patients undergoing Watchman implantation at 8 different centers were categorized into CKD stage 1+2 (n=1089), CKD stage 3 (n=796), CKD stage 4 (n=170), CKD stage 5 (n=69) based on the estimated glomerular filtration rate at baseline. The primary efficacy endpoint included a composite of cardiovascular (CV) mortality, stroke, transient ischemic attack, peripheral thromboembolism (TE), and major bleeding.

Results
A non-significant higher incidence of major peri-procedural adverse events (1.7% vs. 2.3% vs. 4.1% vs. 4.3%) was observed with worsening baseline kidney function (p=0.14). The mean follow-up period was 13 ± 7 months [2226 patient-years (PY)]. In comparison to CKD stage 1+2 as a reference, the incidence of the primary endpoint was significantly higher in CKD stage 3 (log-rank p-value= 0.04), CKD stage 4 (log-rank p-value= 0.01), and CKD stage 5 (log-rank p-value= 0.001) (Fig.1A). A non-significant increase in event rates for stroke/TIA and clinically relevant bleeding was observed among the four groups. LAAO led to a TE risk reduction of 72%, 66%, 62%, and 41% in each group (Fig.1B). The relative risk reduction in the incidence of major bleeding was 58%, 44%, 51%, and 52%, respectively (Fig.1C).

Conclusion
Patients with moderate-to-severe CKD had a higher incidence of the primary composite endpoint. However, the relative risk reduction in the incidence of TE and major bleeding was consistent across CKD groups, irrespective of the very different risk profiles at baseline.
Healthcare utilization and outcomes in atrial fibrillation patients treated by drug therapy versus a catheter ablation strategy
Authors: Martinek M , Crijns H J G M , Essers B , Pruckner G J 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background and Aims
Atrial fibrillation (AF) is the most prevalent arrhythmia, associated with increased mortality and morbidity and causing relevant costs. Treatment options consist of catheter ablation (PVI) and rate or rhythm control drugs (non-PVI).

Methods
We analyze inpatient and outpatient data from the Upper Austrian Health Insurance Fund. Data of patients with a first hospitalization for AF in the years 2005 to 2018 were examined, using propensity score matching (PSM) including all CHA2DS2-VASc variables and working collar.

Results
Out of 21,791 AF patients, PSM identified 1,013 well-matching pairs (PVI and non-PVI). Over a ten-year period, the PVI treatment strategy group reveals significantly higher inpatient and outpatient expenditures (€2,200/year). Positive economic effects can be demonstrated by a 5.1 percentage points (pp) higher employment rate and fewer retirements (7.6pp). Utmost important is the 5.8pp all-cause mortality reduction over 10 years in the PVI treatment strategy.

Conclusions
A PVI based treatment strategy results in higher healthcare expenditures vs. drug therapy alone. Most of these higher costs are caused by the PVI procedures during this period. Thus, more effective and efficient methods are needed to further reduce costs for the intervention and prevent repeat procedures. The benefit of a PVI treatment strategy is seen in higher employment rates, which is crucial from a societal perspective and should be a strong argument for caregivers. We show a significant reduction in all-cause mortality, which we partly attribute to the PVI procedure itself, to a stricter risk factor assessment and treatment, and a tighter medical adherence.
Spontaneous left-sided atypical flutter: revising the mechanisms in patients not submitted to prior linear ablation
Authors: Brito J , Valente Silva B , Alves Da Silva P , Nunes Ferreira A , Lima Da Silva G , Carpinteiro L , Ribeiro J , Cortez-Dias N , J Pinto F , Sousa J 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
The decrease in the use of linear ablation for atrial fibrillation treatment has reduced the frequency of iatrogenic feft-sided atypical flutters (AFl). However, AFl are becoming increasingly frequent, associated with population age and risk factors for atrial scar. Revising the mechanisms of non-iatrogenic AFl may lead to a better procedure workflow.

Purpose
To describe the mechanisms of non-iatrogenic AFl.

Methods
Retrospective single-center study of AFl patients (pts) submitted high-density mapping from 2018 to 2022. Patients submitted to any prior left atrial linear ablation were excluded. Map collection was performed just visualizing the voltage map and a comprehensive workflow was applied for activation map interpretation, starting by facing the mitral annulus and following the sequence of colors to systematically identify all potential circuits, their common-isthmuses, and eventual slow-conduction sites. Entrainment maneuvers were performed to confirm the circuit interpretation if sinus rhythm was not restored with the completion of the planned ablation set.

Results
A total of 59 pts were included (male: 56% male; 67 ± 13 years), 28 previously submitted to atrial fibrillation ablation, restricted to pulmonary vein (PV) isolation. About 88% presented a macro-reentrant mechanism, either restricted to the left atrium (N=50) or biatrial (N=2) and involving 2 or 3 loops in 61% - Figure 1. Perimitral loop was the most frequent reentrant circuit, representing 60% of macro-reentrant arrhythmias (N=30) and exhibiting an evident out-of-proportion predominance of counterclockwise rotations (73% versus 27%). Among perimitral flutters with at least one additional loop, a balanced distribution was recognized of rotations around the left and right PVs (10 versus 10). As a result of the existence of additional loops producing common-isthmuses locations in various atrial regions, the classical inferior mitral isthmus line (from the mitral annulus to the left inferior PV) would only terminate as much as 53% of the perimitral AFl. The mechanism-tailored ablation strategy, particularly targeting the AFl common-isthmuses, resulted in restoration of sinus rhythm in 96.6% of pts (N=57).

Conclusions
In pts not previously submitted to linear ablations, AFl are predominantly caused by macro-reentrant circuits involving a perimitral rotation but not necessarily possible to treat with a conventional mitral isthmus line. With current high-density mapping tools, a comprehensive analysis of the substrate and activation maps and a mechanism-tailored ablation strategy results in an unprecedently high acute success rate.
Symptomatic intermittent ventricular pre-excitation in adult: a monocentric retrospective study
Authors: Robles A G , Palama' Z , Borrelli A , Borrelli A , Scara' A , De Luca L , Grieco D , De Ruvo E , Calo' L , Nesti M , Gianfrancesco D , Bartolomucci F , Penco M , Romano S , Sciarra L 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.
Backgorund: Intermittent ventricular pre-excitation was considered a low-risk marker for sudden death. However, to date some studies do not exclude the existence of accessory pathways (APs) with high-risk intermittent antegrade conductive properties. High-risk features of APs are: ERP/SPERRI ≤250 msec (in basal or during adrenergic stimulus), inducibility of atrioventricular reciprocating tachycardias (AVRT), inducibility of pre-excited atrial fibrillation (AF), multiple APs. For these catheter ablation is recommended.

Purpose
The aim of this retrospective study was to evaluate the existence of a statistically significant difference in the risk characteristics between patients with intermittent pre-excitation (IPX) and with persistent pre-excitation (PPX), from a sample of adults with symptomatic ventricular pre-excitation (Wolff-Parkinson-White Syndrome).

Methods
Between August 2005 and December 2015, 293 adults (age ≥18 years) [males: 183 (62.5%)], without structural heart disease, with signs of ventricular pre-excitation and symptomatic for palpitations underwent an EP study [IPX: 51 (17.4%), males: 31 (60.8%); PPX: 242 (82.6%), males: 152 (62.8%)]. The APs were submitted to catheter ablation if EP study showed inducibility of arrhythmias (AVRT/AF) and, in case of non-inducibility of arrhythmias, if ERP ≤250 msec, in basal or during intravenous infusion of isoproterenol. Additionally, the presence of multiple accessory pathways was assessed during the test.

Results
The 2 groups of patients did not show statistically significant differences in age at the time of EP study [IPX: mean age 37.23±16.89 years Vs PPX: mean age 39.03±16.19 (P-value&gt;0.05)] and gender (IPX male: 60.8% Vs PPX male: 62.8%; P-value&gt;0.05). When measured, there were no statistically significant differences regarding ERP [IPX: mean ERP 260±45.8msec Vs PPX: mean ERP 267.7±59.6msec; P-value&gt;0.05]. The inducibility of arrhythmias (AVRT/AF) was 59.3% in the IPX group (27 patients) vs 38% in the PPX group (92 patients), showing statistically significant differences (P-value&lt;0.05). Multiple accessory pathways were found in 2 patients of the IPX group (3.9%), both females (100%), and in 6 patients of the PPX group (2.5%), of which 2 females (33.3%), not showing statistically significant differences (P-value&gt;0.05).

Conclusion
In our study, patients with IPX did not shown statical significant differences in clinical and electrophysiological features Vs PPX partients. Thus, intermittent ventricular pre-excitation could not absolutely be considered a marker of lower arrhythmic risk.
Psychological stress in postural tachycardia syndrome: results of an online survey
Authors: Firth K , Fedorowski A , Daukantaite D , Hamrefors V 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Postural orthostatic tachycardia syndrome (POTS) is a chronic condition in which patients show a marked increase in heart rate on standing, but also suffer from a range of additional symptoms, which may include fatigue and unrefreshing sleep. A well accepted 10-item survey instrument, the Perceived Stress Scale (PSS; Cohen, et al., 1983), was used to investigate the levels of psychological stress experienced by POTS patients.

Methods
Sixty Swedish patients diagnosed with POTS at a tertiary investigation center were contacted by mail and a link was provided to respondents who signed the informed consent form. A 64-item, on-line survey was developed in five sections. One of the sections consisted of the ten items of the PSS scale. As an example, item three asks: "In the last month, how often have you felt nervous and ‘stressed’?". A five-point Likert scale is used with possible responses ranging from "never" to "very often". This study employed a previously translated Swedish language version, which has been validated in a sample of 3,406 respondents and showed good internal reliability (α =.84) and normative data for a Swedish population (Nordin & Nordin, 2013). Symptoms were measured using the orthostatic hypotension questionnaire (Kaufmann et al. 2012).

Results
Twenty-four POTS patients (22 female gender; mean age 35 years, SD = 8.4) completed the survey. The average age at onset of symptoms was 20 years and four months with patients waiting an average of nine years and five months for a POTS diagnosis. Scores for the PSS ranged from three to 35. The mean PSS score for this cohort was 19.38 (SD = 8.88). Fourteen respondents were in the moderate range for perceived stress (14 to 26), whilst five can be considered to have a low perception of stress and five a high perception. Patients with POTS had a statistically significant higher score for perceived stress (M = 19.38, SD = 8.88, p &lt; .01) than the general population of Sweden (M = 13.96, SD = 5.63). However, there was no correlation between perceptions of stress and symptom severity measured by the orthostatic hypotension questionnaire.

Conclusions
Swedish POTS patients have higher levels of perceived stress, similar to other disease states such as chronic pain and multiple sclerosis (Table 1). However, this survey found no correlation between perceptions of stress and symptom severity.
Therapeutic options for syncope: a meta-analysis of trials with and without placebo control
Authors: Kaza N , Sorbini M , Johal M , Liu Z , Porter B , Nowbar A , Levy S , Dani M , Taraborelli P , Eardley P , Whinnett Z I , Francis D P , Shun-Shin M , Lim P B , Keene D 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
8% of the population suffer recurrent episodes of syncope which can cause physical injury and psychological morbidity. The extent to which therapeutic options effectively reduce syncope recurrence beyond placebo remain unclear.

Methods
We performed a meta-analysis of randomised trials including pharmacological, cardiac pacing and physical interventions for syncope. We assessed the effect of these therapeutic interventions on clinical syncope recurrence. We stratified the trials by use of placebo control.

Results
There were 50 eligible trials: 22 pacing, 19 pharmacological and 9 of physical interventions including 3,975 patients.
Trials assessing syncope recurrence with placebo control were neutral for Beta-Blockers (RR 1.11, 95% CI 0.85 to 1.45, p=0.36), Fludrocortisone, (RR 0.83, 95% CI: 0.63 to 1.11 p=0.83) and conventional dual-chamber pacing (RR 0.81, 95% CI 0.61 to 1.09 p=0.287). However, they were favourable for Selective Serotonin Reuptake Inhibitors [SSRIs] (RR 0.40, 95% CI 0.25 to 0.63 p&lt;0.001), Midodrine (RR 0.70, 95% CI 0.53 to 0.94, p=0.016) and Closed-Loop-Stimulation (CLS) pacing (RR 0.21, 95% CI 0.12 to 0.34, p &lt; 0.001).
Non-placebo-controlled trials reported significant benefit for every category of therapy including conventional dual-chamber pacing, medicines (Beta-Blockers, Midodrine and Oral rehydration salts) and physical interventions including tilt-training.
Three categories of therapy have been trialled with and without placebo control: the non-placebo-controlled studies showed significantly different results from their placebo-controlled counterparts (beta-blockers p=0.024, midodrine p=0.006, dual-chamber pacing p=0.017) (figure 2).

Conclusion
Under placebo-controlled conditions, CLS pacing reduces risk of syncope recurrence by ~75%, whereas conventional pacing does not. SSRIs and midodrine also show significant efficacy under placebo-controlled conditions. Without placebo control, trials consistently show artefactually larger benefits. Future non-placebo-controlled trials for syncope should not be conducted.
Pharmacological inducibility of short-coupled Purkinje ectopy in patients with spontaneous short-coupled ventricular fibrillation
Authors: Laredo M , Duchateau J , Waintraub X , Gandjbakhch E , Marijon E , Lavergne T , Haissaguerre M 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
In a subset of patients with idiopathic ventricular ﬁbrillation (IVF), the cause is identified as short-coupled premature ventricular complexes (ScPVCs), which mostly originate from Purkinje cells, and are often short-living and undetected. There is no consistent test allowing identification of patients vulnerable to this malignant arrhythmia. We aimed at evaluating sodium channel blocker (NaBl) testing in patients who survived IVF associated with SCPVCs.

Methods
We retrospectively reviewed data of 112 patients at 3 centers, with the diagnosis of IVF associated with spontaneous and documented scPVCs. No patient from the previous report was included. We analyzed all patients who underwent NaBl tests during evaluation of IVF. An arrhythmogenic NaB test was defined as the occurrence of ≥10 scPVCs and/or ≥ 1 repetitive form (couplet, triplet, run) during the test, without spontaneous scPVC at baseline. We defined scPVCs as an R-on-T pattern PVC. We evaluated the occurrence of scPVC during NaB infusion, the arrhythmia pattern and we compared the characteristics of the arrhythmogenic versus non-arrhythmogenic response groups. Data regarding anti-arrhythmic drug treatment and follow-up were collected at each center.

Results
In total, 48 patients were included (Table). The NaB tests were performed using ajmaline 1mg/kg/5 or 10min, or flecainide 2mg/kg/10min. Overall, an arrhythmogenic NaB test occurred in 23 of 48 (48%) patients. Isolated ScPVCs were observed in 11 patients, couplet/triplets in 10, and runs in 6. The arrhythmogenic response was reproduced in 5/5 patients who had a second NaB test during scPVC mapping before catheter ablation. There were no signiﬁcant differences between patients with arrhythmogenic or non-arrhythmogenic NaB tests in all baseline clinical variables tested including VF burden (Table). All patients were followed at least 1 year after initial diagnosis and NaB test. Under hydroquinidine (600 or 900mg/day), appropriate defibrillator shocks occurred in 7 of 8 patients with arrhythmogenic NaB test; whereas shocks occurred only in 2 of 11 patients with non-arrhythmogenic NaB test (P=0.02).

Conclusion
Sodium blockers unravel scPVCs in up to 50% of patients with IVF and may therefore represent a valuable tool to detect a potential cause for sudden cardiac death (SCD) or unexplained syncope. Additionally, the arrhythmogenic response to NaB may be associated with the success of hydroquinidine in preventing IVF recurrence, a finding that suggests the existence of distinct scPVCs phenotypes and that may have important therapeutic implications. Further functional and genetical investigations are warranted to explore the mechanisms underlying this association.
The use of cardiovascular modes of death in the office of national statistics mortality statistics
Authors: Westaby J , Gabrawi A M , Sheppard M N 
Published: May 2023

Abstract
Funding Acknowledgements: Type of funding sources: Other. Main funding source(s): Cardiac Risk in the Young
The office for national statistics (ONS) holds a record of all causes of death in England and Wales according to the International Classification of Diseases 10th Revision. In some cases, a mode of death, such as arrhythmia, may be given. We aimed to quantify the proportion of cardiovascular deaths being coded as a mechanism of death from the ONS.
We analysed the ONS records from 2013 – 2021. There were 4,852,897 deaths overall, of which, 836,741 (17.24%) were cardiovascular. Of these, 103,160 (12.33%) were labelled as mechanisms and 35,784 (4.28%) were nonspecific causes. The most common modes being used were arrhythmia (56,291 (6.7%)) and heart failure (46787 (5.6%)). The most common nonspecific codes being used were myocardial degeneration (12,192 (1.46%)), unascertained (10,605 (1.27%)) and cardiomegaly (6,573 (0.79%)).
Modes of death as opposed to causes of death are being used in a notable proportion of cardiac deaths and this is increasing. Modes of death do not aid in screening of blood relatives for inherited cardiac conditions. Causes should be listed as an underlying disease process such as ischaemic heart disease (IHD) or hypertrophic cardiomyopathy. This enables screening to be focussed on specific diseases. The use of a mode of death as opposed to a specific disease should prompt a referral for autopsy.
ICD-11 has coding for SADS and arrhythmogenic cardiomyopathy (ACM) and our findings highlight the importance of the transition to this update to allow accurate establishment of the burden of disease of these two important genetic conditions.