bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1898Prevalence and risk of DOACs inappropriate dosing in atrial fibrillation. An analysis of the Swiss-AF and BEAT-AF registries
Authors: Montrasio G , Coslovsky M , Wiencierz A , Baumgartner C , Rodondi N , Kuehne M S , Moschovitis G , Preiss H , Reiner M F , De Perna M L , Conen D , Osswald S , Beer J H , Koepfli P 
Published: October 2019

Abstract

Background
Direct oral anticoagulants (DOACs) have a similar efficacy in terms of stroke and mortality reduction as compared to Vitamin K-Antagonists (VKAs) and improved safety with regards to intracranial haemorrhage in patients with non-valvular atrial fibrillation (AF). Dose of DOACs needs to be adjusted according to age, weight, renal function and concomitant medication. Yet, off-label dosages have been reported in 11 - 45% of patients (on average 20%).

Purpose
To assess the prevalence of inappropriate DOAC-dosing according to the official prescribing information in two large prospective Swiss AF cohorts (Swiss-AF and BEAT-AF) and to evaluate its correlation with adverse clinical outcomes.

Methods
All 3267 patients taking oral anticoagulants were stratified at baseline as receiving DOACs (adequately dosed, under- or overdosed) or VKAs. Appropriateness of DOAC dosing was assessed based on age (≥80 years), weight (≤60kg) and renal function (serum creatinine ≥133μmol/l [apixaban]; creatinine clearence ≤50ml/min [all other DOACs]). Clinical outcomes were collected during a median follow-up of 2.96 years. Major adverse clinical events (MACE) consisted of a combination of myocardial infarction, cardiac death, ischemic stroke and systemic embolism. Safety was assessed by occurrence of any bleeding event.

Results
1902 patients (58%) were on VKAs and 1365 on DOACs (42%). In the DOAC group, 1149 patients received a dose consistent with drug labelling (84%), 133 (10%) received an inappropriately high and 83 (6%) an inappropriately low dose. Overdosed patients were older than those adequately treated and more likely female, had a lower BMI and a higher CHA2DS2-VASc score (4 vs. 3 points) (p<0.001 for all). Underdosed patients were more likely to have concomitant antiplatelet therapy (p<0.001). Both off-label groups were more likely to have a history of coronary artery disease, heart failure and chronic kidney disease (p<0.001). Kaplan-Meier cumulative incidence rates for the first occurrence of MACE or bleedings are provided in Figure 1. Overdosed patients had an almost two-fold higher risk of bleeding (9.0 vs. 5.0 events per 100 patient-years compared to correctly dosed DOACs and to VKAs) and a higher rate of MACE (5.1 vs. 2.3 events per 100 patient years compared to correctly dosed DOACs and 5.1 vs. 3.4 compared to VKAs). Underdosing did not seem to be associated with a relevant increase in ischemic or bleeding events as compared to correctly dosed DOACs and VKAs (see Figure 1).
Figure 1. Kaplan-Meier incidence curves

Conclusion
Inadequate DOACs dosing was found in 1 in 6 patients and correlated with a higher burden of comorbidities at baseline. Underdosing correlated with concomitant antiplatelet therapy. Overdosing was associated with adverse clinical outcome for ischemic and bleeding events.
P1899Heparin and low-molecular-weight heparin switch associated with an increase in bleeding complications in patients on apixaban undergoing catheter ablation: The AMPER ABLATION study
Authors: Amara W , Garcia R , Mansourati J , Taieb J , Gandjbackh E , Dompnier A , Gorka H , Zannad N , Da Costa A , Sacher F , Jourda F , Fromentin S , Cheggour S , Mlayeh D , Milhem A 
Published: October 2019

Abstract

Background
The aim of this study was to identify the factors associated with bleeding complications in patients taking apixaban and undergoing a catheter ablation in everyday clinical practice.

Methods
AMPER ABLATION is a multicenter, observational, prospective study of patients with non valvular atrial fibrillation (AF) undergoing a catheter ablation. Eligible patients had been taking apixaban (2.5 or 5 mg twice daily) for ≥3 weeks before the procedure, and were followed for 30 days afterwards.

Results
A total of 595 patients (65 [interquartile range 59, 72] years, 67% male, mean CHA2DS2-VASc score 1.85±1.37) were enrolled at 25 academic/nonacademic centers in France; 524 patients (88%) were receiving apixaban 10 mg/day and 71 (12%) 5 mg/day. 323 patients (54%) underwent an AF ablation, and 272 (46%) an atrial flutter (AFL) ablation. The most prevalent concomitant disorders were hypertension (51% of patients), diabetes (15%) and vascular disease (10%). Mean creatinine concentration was 1.06±0.28 mg/dL, median weight was 83±18 kg and mean creatinine clearance (Cockcroft-Gault) was 82±34 mL/min. The management of apixaban in the periprocedural period was left to the investigator's preference. Overall, 264 patients were switched to unfractionated heparin or enoxaparin (238 for AF ablations and 26 for AFL ablations). The median duration of switch was 29 hours. Complications were reported at 30 days, and included 12 bleeding events (1 tamponade needing drainage, 1 pericardial effusion without drainage, 7 International Society on Thrombosis and Haemostasis [ISTH] non major bleedings for AF ablations and 1 pericardial effusion without drainage, and 2 ISTH non major bleedings for AFL ablations) and 1 embolic event (non disabling stroke for an AF ablation). Comparing patients with and without a bleeding event revealed a higher rate of heparin or low-molecular-weight heparin (LMWH) switching in patients with a bleeding event (60% vs 35%; p=0.02). A switch to heparin or LMWH was the only factor associated with an increase rate of bleeding (odds ratio 2.5; [CI 95%; 1.1, 7.1]; p=0.01).

Conclusion
Heparin or LMWH switch in the periprocedural AF and AFL-ablation period is associated with an increased rate of bleeding complications at 30 days.

Acknowledgement/Funding
Financial support from BMS
P1900Amiodarone treatment duration and reasons for permanent drug discontinuation in patients with atrial fibrillation
Authors: Mihajlovic M , Mihajlovic A , Marinkovic M , Kovacevic V , Vajagic L , Kocijancic A , Mujovic N , Potpara T 
Published: October 2019

Abstract

Background and purpose
Amiodarone is commonly use in patients with atrial fibrillation (AF), but the organ toxicity side effects limit its long-term use. We investigated the rates of and reasons for permanent amiodarone discontinuation among patients with AF in contemporary clinical practice.

Methods
A single-centre, ongoing, registry-based observational longitudinal study included consecutive AF patients prescribed with amiodarone in our hospital from January 2015 to December 2017. All patients underwent a loading protocol of 400–600 mg of amiodarone daily for 1–2 weeks, followed by 200–400mg daily for 4–8 weeks and 200mg daily or 1000mg weekly thereafter.

Results
Of 657 AF patients taking amiodarone (Mean age 62.2±11.0, female n=215 (32.6%), hypertension n=504 (76.7%), diabetes mellitus n=107 (16.3%), coronary arterial disease n=139 (19.8%), History of Myocardial infarction 86 (13.1%), Stroke/TIA 60 (9.1%), chronic kidney disease 157 (23.9%)), the drug was permanently discontinued in total of 248 patients (37.7%). The reasons for amiodarone discontinuation are shown in Figure. On multivariable Cox-regression analysis, physician's decision (HR 5.6; 95% CI 3.9–7.9, p<0.001) and amiodarone side effects (HR 3.9; 95% CI 2.9–5.1, p<0.001) were significantly associated with permanent amiodarone discontinuation.
The overall time to discontinuation was 23.2±24.1 months. Compared with others, time to discontinuation was shorter in patients post AF ablation (17.3±21.3 vs 24.5±24.5, p=0.05), longer in those with AF progression (29.2±31.0 vs 20.9±20.3, p=0.014) and similar in patients with amiodarone side effects (23.7±17.7 vs 23.0±26.8, p=0.813). Pulmonary toxicity and proarrhythmia were not observed among study patients (Figure).
Chart 1

Conclusion
Our study showed that permanent discontinuation of amiodarone in contemporary clinical practice was due to the drug side effects in 12% of amiodarone-treated AF patients, occurring after a mean 2-year treatment course. The most prevalent side effect was thyroid dysfunction, whereas the prevalence of proarrhythmic effect was low. Notably, physician's fear of complications (which may not always be justified), also was an independent driver of permanent amiodarone discontinuation. More data are needed to inform optimal amiodarone use in AF patients in daily practice.
P1903Efficacy and safety of dronedarone after recent cardioversion in patients with atrial fibrillation/flutter: a post-hoc analysis of the EURIDIS/ADONIS trials
Authors: Thind M , Crijns H J , Naccarelli G V , Reiffel J A , Corp Dit Genti V , Wieloch M , Koren A , Kowey P R 
Published: October 2019

Abstract

Background
Cardioversion is commonly performed prior to antiarrhythmic drug initiation for atrial fibrillation/flutter (AF). There are limited data describing baseline differences in patients requiring cardioversion to maintain sinus rhythm compared to those who do not. Likewise, response to antiarrhythmic drugs, including dronedarone, specifically in patients requiring cardioversion has not been well defined.

Purpose
To evaluate efficacy and safety of dronedarone versus placebo in patients with non-permanent AF who had cardioversion within 5 days prior to randomization in EURIDIS/ADONIS.

Methods
To qualify for enrolment in EURIDIS/ADONIS patients were required to be in sinus rhythm for at least 1 hour preceding randomization. Of 1237 patients randomized (2:1 dronedarone to placebo), 364 needed cardioversion for study entry (dronedarone 243, placebo 121). AF recurrence was evaluated by ECG obtained during study visits, scheduled transtelephonic monitoring, or at symptom recurrence.

Results
Cardioversion patients were more likely to have rheumatic heart disease, valvular heart disease, any structural heart disease, and heart failure. Nonetheless, the median time to 1st AF recurrence was longer for dronedarone versus placebo both in cardioversion patients (50 versus 15 days, hazard ratio 0.76, 95% CI 0.59, 0.97) and no cardioversion patients (150 versus 77 days, hazard ratio 0.76, 95% CI 0.64, 0.90), as was time to 1st symptomatic recurrence (cardioversion: 347 versus 87 days, hazard ratio 0.65, 95% CI 0.49, 0.87; no cardioversion: 288 versus 120 days, hazard ratio 0.74, 95% CI 0.62, 0.90) (Figure 1). There was a trend towards fewer 1st AF hospitalizations within 12 months for dronedarone versus placebo (7.8 versus 12.4%, hazard ratio 0.60, 95% CI 0.31, 1.18 in cardioversion patients; 8.4 versus 10.4%, hazard ratio 0.74, 95% CI 0.47, 1.17 in no cardioversion patients). In cardioversion patients, rates of treatment-emergent adverse events with dronedarone versus placebo were 64 versus 66%, serious treatment-emergent adverse events were 19 versus 26%, permanent discontinuations were 9 versus 6%, and deaths were 0 versus 1%.

Conclusions
1) Cardioversion-requiring patients have more baseline structural heart disease and overall shorter time to AF recurrence. 2) Dronedarone effectively delayed 1st AF recurrence versus placebo in patients with or without recent cardioversion. 3) Safety of dronedarone in cardioversion patients was similar to placebo and overall observations from EURIDIS/ADONIS despite baseline differences in comorbidities.

Acknowledgement/Funding
Sanofi, New York, New York, United States of America
P1921Impact of cryoballoon freeze duration on long-term durability of pulmonary vein isolation in atrial fibrillation: insights from Re-mapping procedures (the ICE Re-map study)
Authors: Chen S , Schmidt B , Bordignon S , Perrotta L , Bologna F , Chun K R J 
Published: October 2019

Abstract

Background
Second-generation cryoballoon (CB2) represents a powerful pulmonary vein isolation (PVI) tool. Recently, the randomized time-to-effect guided (ICE-T) CB2 strategy targeting a 240s single freeze demonstrated fast and efficient PVI. To further optimize safety and efficacy, a shortened 3min freeze duration has been suggested but PVI durability remains unclear.

Methods
Between May 2013 and December 2017 all CB2 ablations followed the ICE-T concept (target-freeze: 240s or 180s). Patients undergoing a second procedure for arrhythmia recurrence were analyzed. Two groups were defined based on the index freeze duration (group 240s vs. group 180s). In all repeat procedures a 3D left-atrial map was obtained. Durability of PVI and localization of conduction gaps were compared.

Results
A total of 106/788 (13%) patients underwent a second procedure (group 240s: 80/604 vs. group 180s: 26/184) after a mean of 377 days. There was no difference regarding PV occlusion and time-to-isolation in the index procedure between two groups. No major complications occurred. During the second procedure significantly more patients demonstrated durable isolation of all PVs in group 240 (61% vs 35%, p=0.02) along with a significantly increased rate of PVI durability (88% vs. 69%, per vein, p<0.001). Left sided PVs did significantly benefit from 240s freezes (reconnection LSPV: 6% vs 27%, p=0.004, LIPV: 14 vs. 39%, p=0.006).

Conclusions
The ICE-T strategy is associated with a high rate of durable PVI in patients with arrhythmia recurrence. Target freeze duration of 240s vs. 180s is associated with significantly increased lesion durability, particularly at left sided PVs, without increasing complications.
P1938In vitro characterization of a novel PI 3-kinase inhibitor for growth factor-induced effects in pulmonary artery smooth muscle cells
Authors: Berghausen E M , Moeller F , Vantler M , Hirsch E , Baldus S , Rosenkranz R 
Published: October 2019

Abstract

Rationale
Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling in pulmonary arterioles. Increased activation of receptor tyrosine kinase (RTK)-mediated signaling pathways lead to increased proliferation and chemotaxis of pulmonary arterial smooth muscle cells (PASMCs). In previous studies, we identified phosphatidylinositol-3-kinase (PI3K) as a key enzyme for these processes. Since systemic PI3K inhibition is potentially associated with undesired side effects, we here for the first time tested the efficacy of the novel PI3K inhibitor CL27c to impede growth factor-mediated cellular effects in human PASMCs. CL27c is topically applicable and as a prodrug it is intracellularly activated and thus offers optimal efficacy in target cells while at the same time minimizing undesired effects in non-target cells.

Methods
Using Western blotting and immunohistochemistry, activation of the central PI3K effector AKT in human and murine lung tissue was investigated. Quantification of cell proliferation was performed by 5-bromo-2-deoxyuridine (BrdU) incorporation assay. PASMCs were incubated with CL27c [0.1; 0.3; 1; 3; 10μM] and stimulated either with PDGF-BB [30ng/ml] or with a growth factor combination (GFC) [PDGF-BB 30ng/ml, FGF 2ng/ml, EGF 0.5ng/ml, insulin 0.5μg/ml, FCS 5%]. Chemotaxis was quantified using modified Boyden chambers. The signal transduction cascade was investigated by Western blotting.

Results
Analysis of AKT activation revealed hyperphosphorylation in both the vascular wall and complete lung homogenates from PAH patients and hypoxia-treated mice. Examination of the mitogenic signal transduction revealed a markedly reduced phosphorylation of AKT and GSK3β in CL27c pretreated PASMCs. In addition, central cell cycle events, such as expression of cyclin D1, were reduced. This was in line with a CL27c concentration-dependent significant reduction of PDGF- and GFC-induced proliferation (control: 2.53±0.26 vs. CL27c: 0.73±0.14 and control: 5.27±0.61 vs. CL27c: 2.80±0.71 both at 10μM, p<0.001). Furthermore, PDGF- and GFC-induced chemotaxis were as well significantly reduced (100% ± 19 vs. CL27c: 24.43% ± 8.58 and 100% ± 5.76 vs CL27c: 25.23% ± 10.57 at 10μM p<0.001).

Conclusion
These results indicate that CL27c reduces both proliferation and chemotaxis of PASMCs. As these processes play a key role in the development and progression of PAH, this approach is currently being investigated in preclinical models for its therapeutic potential. This “prodrug” approach could avoid non-specific effects and systemic side effects of Pan-PI3K inhibition, especially since the substance is suitable for topical application (inhalation). Thus, CL27c represents a promising treatment option.
P1949Changes in prevalence patients with arterial hypertension in Russia
Authors: Badin Y , Fomin I V , Polyakov D S , Yakushin S S , Smirnova E A , Galyavich A S , Kamalov G M , Kechedzhieva S G , Koziolova N A , Malchikova S V , Ionova T S 
Published: October 2019

Abstract

Aim
The present study shows the dynamics of the prevalence different grades of AH and treatment coverage over15 years of observation.

Methods
8740 apartments were randomized in 2002 year in eight regions of Russia and 19449 individuals were included. Re-examination was carried out in 2017 year. The representative sample was separated in four groups: Grade 0 – individuals with systolic blood pressure (BP) <140 mm Hg and diastolic blood pressure <90 mm Hg; and three Grades of arterial hypertension (AH) in accordance with European guidelines. Also, we select patient with and without antihypertensive drug treatment (AHDT).

Results
The mean age individuals was 44.4±19.3 years in 2002 year. Grade 0 had 63.3% participants (mean age 36.5±17.1 y.), Grade 1 – 19.5% (mean age 55.2±15.4 y.), Grade 2 – 11.7% (mean age 60.6±13.5 y.) and Grade 3 – 5.6% (mean age 62.4±12.8 y.). 3.0% participants had AHDT and blood pressure meets Grade 0. Patients with AH Grade 1 used drugs in 25.5% cases, with Grade 2 – 49.4% and with Grade 3 – 60.8% patients respectively. The mean age of participants with AHTD was significantly higher than mean age group without AHTD in Grade 0, 1 and 2 (p<0.001). In group Grade 3 mean age was not difference (p=0.16). The mean age individuals (51.3±16.9 y.) in 2017 year was significantly higher on 6.9 years than mean age in 2002 year (p<0.001). The proportion of patients with AHDT in all grades groups in sample 2017 year were significantly higher than in sample 2002 year (Table). The prevalence of AH in 2002 y. amounted to 38.6%. In 2017 y. prevalence of AH was significantly higher – 41.4% (p<0.001).
Structure of samples Grade 2002 2017 AHDT Mean age AHDT P value Mean age 0 63,3% No 35,8±16,8 70,1% 42,6±13,9 Yes 3,0% 57,4±14,5 16,3% <0,001 63,6±12,0 1 19,5% No 53,3±15,7 23,6% 57,3±13,3 Yes 25,5% 60,9±13,0 68,4% <0,001 66,3±11,3 2 11,7% No 58,5±14,2 5,4% 58,0±14,9 Yes 49,4% 62,7±12,3 80,6% <0,001 66,5±11,5 3 5,6% No 61,7±13,9 1,0% 63,6±17,6 Yes 60,8% 62,8±12,0 71,1% 0,03 66,0±12,8 ALL 100% 44,4±19,3 100% 51,3±16,9 AHDT: antihypertensive drug treatment.

Conclusion
Over 15 years follow up period the prevalence of hypertension in Russia increased to 41.4%, but the effectiveness of therapy remains low.
P1953Risk of upper gastrointestinal bleeding following myocardial infarction: a novel prediction model for assessing appropriateness of proton pump inhibition therapy
Authors: Sehested T S G , Blanche P , Hansen P W , Charlot M G , Torp-Pedersen C , Fosboel E L , Gislason G H , Gerds T A , Carlson N 
Published: October 2019

Abstract

Background
Upper gastrointestinal bleeding following myocardial infarction continues to be a severe complication associated with increased mortality; however, bleeding events might be avoided by appropriate therapy with proton pump inhibitors.

Purpose
To develop and validate a prediction model aimed at identifying patients at increased risk of upper gastrointestinal bleeding following myocardial infarction.

Methods
Based on multiple nationwide Danish registers, all patients initiating dual antiplatelet or anticoagulant therapy in combination with antiplatelet following myocardial infarction between 2003 and 2016 were identified. Primary outcome of interest was one-year risk of upper gastrointestinal bleeding. A derivation cohort including all patients between 2003 and 2013 was selected, whereas patients identified between 2014 and 2016 was employed for internal validation. Multiple logistic regression was used to predict person specific risks based on age, history of gastrointestinal bleeding or peptic ulcer, anaemia or gastrointestinal cancer, use of nonsteroidal anti-inflammatory drugs, oral anticoagulants, selective serotonin reuptake inhibitors or loop diuretics. We compared our model with the European Society of Cardiology (ESC) guideline recommendation on gastrointestinal bleeding risk assessment.

Results
A total of 61 543 patients with myocardial infarction were identified for the study. In the total cohort, the median age was 68 years (IQR: 58–77), 85.0% (52 334) underwent coronary angiography, 2.6% (1 608) had a history of gastrointestinal bleeding and 7.1% (4 354) used oral anticoagulants. The average one-year risk of upper gastrointestinal bleeding was 1.04% (95% CI: 0.95–1.14%), and mean predicted risk of the model was 1.04% (IQR: 0.64–1.26%). The discriminative ability of the model evaluated by area under the curve was 74.2% (95% CI: 66.9–78.6%) in the validation cohort. The proposed risk model demonstrated improved sensitivity and specificity at the specific threshold of the ESC risk schemes (Figure 1). Results remain principally unchanged regardless of inclusion or exclusion of patients initiating proton pump inhibitors at baseline. Furthermore, using cross-validation for the model evaluation produced similar discrimination results.
Figure 1

Conclusion
Based on nationwide registers a novel prediction model aimed at identifying patients at increased risk of upper gastrointestinal bleeding was developed and validated; the model observed moderate discrimination in the validation cohort providing possible benefit for clinicians in terms of communicating absolute risk to the patients and determining the appropriateness of initiating preventive therapy.

Acknowledgement/Funding
The Danish Heart Foundation
P2244Anomalies in women of the aortic arch in Turner syndrome as an important risk factor for premature morbidity and mortality
Authors: Klaskova E , Kapralova S , Zapletalova J , Tudos Z , Adamova K 
Published: October 2019

Abstract

Introduction
Turner syndrome (TS) represents the most common chromosomal disorder in women being, caused by the absence or structural abnormality of X chromosome. Congenital heart defects affect up to 50% of females with TS.Prevalence of coarctation of the aorta in TS has been estimated 7–18% depending on imaging method. Introduction of cardiac magnetic resonance imaging (MRI) into the routine practice markedly increased the detection rate of anomalies of the aortic arch such as elongated transverse aortic arch with abnormal curvature, i.e.kinking, pseudocoarctation or aberrant right subclavian artery. Aims of study was to estimate prevalence of anomalies of the aortic arch in our study group according to the karyotype.

Methods and patients
Study group consisted of 67 patients with TS at the age 7.3 yrs (range 0.1 - 16.5 yrs.). Complete cardiovascular examination (echocardiography, MRI of the heart and great vessels) and cytogenetic examination were performed in each of our study patient.

Results
The prevalence of anomalies of the aortic arch was 15% (10 patients). Four of them had elongated transverse aortic, coarctation of the aorta was found in three cases, aberrant right subclavian artery in two patients and one girl had right aortic arch. 45,X cell line was presented in every patient with anomaly of the aortic arch, none of them had structural abnormality of X chromosome.

Conclusions
Compared with the general population, the prevalence of CoA and the others anomalies of the aortic arch is significantly higher in women with TS, especially with 45,X cell line. As far as CoA is considered to be one of the major risk factor for aortic dissection detailed cardiovascular screening focused on thoracic aorta anomalies seems to be crucial in order to prevent it.

Acknowledgement/Funding
Supported by Ministry of Health, Czech Republic - MZ VES 2017 (Reg. No. NV17-29111A).