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1.
  • Roselli, Carolina, et al. (författare)
  • Multi-ethnic genome-wide association study for atrial fibrillation
  • 2018
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
  • Tidskriftsartikel (refereegranskat)abstract
    • Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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  • d'Alessandro, Elisa, et al. (författare)
  • Thrombo-Inflammation in Cardiovascular Disease : An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis
  • 2020
  • Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 120:4, s. 538-564
  • Tidskriftsartikel (refereegranskat)abstract
    • Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.
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  • Schnabel, Renate B., et al. (författare)
  • Searching for Atrial Fibrillation Poststroke : A White Paper of the AF-SCREEN International Collaboration
  • 2019
  • Ingår i: Circulation. - 1524-4539. ; 140:22, s. 1834-1850
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non-vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non-vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.
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  • Hendriks, Jeroen, et al. (författare)
  • Integrated specialized atrial fibrillation clinics reduce all-cause mortality: post hoc analysis of a randomized clinical trial
  • 2019
  • Ingår i: Europace. - : OXFORD UNIV PRESS. - 1099-5129 .- 1532-2092. ; 21:12, s. 1785-1792
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims An integrated chronic care programme in terms of a specialized outpatient clinic for patients with atrial fibrillation (AF), has demonstrated improved clinical outcomes. The aim of this study is to assess all-cause mortality in patients in whom AF management was delivered through a specialized outpatient clinic offering an integrated chronic care programme. Methods and results Post hoc analysis of a Prospective Randomized Open Blinded Endpoint Clinical trial to assess all-cause mortality in AF patients. The study included 712 patients with newly diagnosed AF, who were referred for AF management to the outpatient service of a University hospital. In the specialized outpatient clinic (AF-Clinic), comprehensive, multidisciplinary, and patient-centred AF care was provided, i.e. nurse-driven, physician supervised AF treatment guided by software based on the latest guidelines. The control group received usual care by a cardiologist in the regular outpatient setting. After a mean follow-up of 22months, all-cause mortality amounted 3.7% (13 patients) in the AF-Clinic arm and 8.1% (29 patients) in usual care [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.23-0.85; P = 0.014]. This included cardiovascular mortality in 4 AF-Clinic patients (1.1%) and 14 patients (3.9%) in usual care (HR 0.28; 95% CI 0.09-0.85; P = 0.025). Further, 9 patients (2.5%) died in the AF-Clinic arm due to a non-cardiovascular reason and 15 patients (4.2%) in the usual care arm (HR 0.59; 95% CI 0.26-1.34; P = 0.206). Conclusion An integrated specialized AF-Clinic reduces all-cause mortality compared with usual care. These findings provide compelling evidence that an integrated approach should be widely implemented in AF management.
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7.
  • Hohnloser, Stefan H., et al. (författare)
  • Effect of dronedarone on cardiovascular events in atrial fibrillation
  • 2009
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 360:7, s. 668-78
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Dronedarone is a new antiarrhythmic drug that is being developed for the treatment of patients with atrial fibrillation. METHODS: We conducted a multicenter trial to evaluate the use of dronedarone in 4628 patients with atrial fibrillation who had additional risk factors for death. Patients were randomly assigned to receive dronedarone, 400 mg twice a day, or placebo. The primary outcome was the first hospitalization due to cardiovascular events or death. Secondary outcomes were death from any cause, death from cardiovascular causes, and hospitalization due to cardiovascular events. RESULTS: The mean follow-up period was 21+/-5 months, with the study drug discontinued prematurely in 696 of the 2301 patients (30.2%) receiving dronedarone and in 716 of the 2327 patients (30.8%) receiving placebo, mostly because of adverse events. The primary outcome occurred in 734 patients (31.9%) in the dronedarone group and in 917 patients (39.4%) in the placebo group, with a hazard ratio for dronedarone of 0.76 (95% confidence interval [CI], 0.69 to 0.84; P<0.001). There were 116 deaths (5.0%) in the dronedarone group and 139 (6.0%) in the placebo group (hazard ratio, 0.84; 95% CI, 0.66 to 1.08; P=0.18). There were 63 deaths from cardiovascular causes (2.7%) in the dronedarone group and 90 (3.9%) in the placebo group (hazard ratio, 0.71; 95% CI, 0.51 to 0.98; P=0.03), largely due to a reduction in the rate of death from arrhythmia with dronedarone. The dronedarone group had higher rates of bradycardia, QT-interval prolongation, nausea, diarrhea, rash, and an increased serum creatinine level than the placebo group. Rates of thyroid- and pulmonary-related adverse events were not significantly different between the two groups. CONCLUSIONS: Dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with atrial fibrillation. (ClinicalTrials.gov number, NCT00174785.)
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  • Kowey, Peter R, et al. (författare)
  • Efficacy and safety of celivarone, with amiodarone as calibrator, in patients with an implantable cardioverter-defibrillator for prevention of implantable cardioverter-defibrillator interventions or death : the ALPHEE study
  • 2011
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 124:24, s. 2649-2660
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Celivarone is a new antiarrhythmic agent developed for the treatment of ventricular arrhythmias. This study investigated the efficacy and safety of celivarone in preventing implantable cardioverter-defibrillator (ICD) interventions or death. METHODS AND RESULTS: Celivarone (50, 100, or 300 mg/d) was assessed compared with placebo in this randomized, double-blind, placebo-controlled, parallel-group study. Amiodarone (200 mg/d after loading dose of 600 mg/d for 10 days) was used as a calibrator. A total of 486 patients with a left ventricular ejection fraction ≤40% and at least 1 ICD intervention for ventricular tachycardia or ventricular fibrillation in the previous month or ICD implantation in the previous month for documented ventricular tachycardia/ventricular fibrillation were randomized. Median treatment duration was 9 months. The primary efficacy end point was occurrence of ventricular tachycardia/ventricular fibrillation-triggered ICD interventions (shocks or antitachycardia pacing) or sudden death. The proportion of patients experiencing an appropriate ICD intervention or sudden death was 61.5% in the placebo group; 67.0%, 58.8%, and 54.9% in the celivarone 50-, 100-, and 300-mg groups, respectively; and 45.3% in the amiodarone group. Hazard ratios versus placebo for the primary end point ranged from 0.860 for celivarone 300 mg to 1.199 for celivarone 50 mg. None of the comparisons versus placebo were statistically significant. Celivarone had an acceptable safety profile. CONCLUSIONS: Celivarone was not effective for the prevention of ICD interventions or sudden death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00993382.
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  • van der Velden, Rachel M. J., et al. (författare)
  • Adherence to a handheld device-based atrial fibrillation screening protocol is associated with clinical outcomes
  • 2024
  • Ingår i: HEART. - 1355-6037 .- 1468-201X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To evaluate adherence and adherence consistency to the handheld ECG device-based screening protocol and their association with adverse cerebral and cardiovascular outcomes in two systematic atrial fibrillation (AF) screening programmes.Methods In 2012 (Systematic ECG Screening for Atrial Fibrillation Among 75-Year Old Subjects in the Region of Stockholm and Halland, Sweden (STROKESTOP) study) and 2016 (Stepwise mass screening for atrial fibrillation using N-terminal pro b-type natriuretic peptide (STROKESTOP II) study), half of all 75- and 76-year-old inhabitants of up to two Swedish regions were invited to participate in a systematic AF screening programme. Participants were instructed to perform 30-second measurements twice daily in STROKESTOP and four times daily in STROKESTOP II for 2 weeks. Adherence was defined as the number of measurements performed divided by the number of measurements asked, whereas adherence consistency was defined as the number of days with complete registrations.Results In total, 6436 participants (55.7% female) from STROKESTOP and 3712 (59.8% female) from STROKESTOP II were included. Median adherence and adherence consistency were 100 (92-100)% and 12 (11-13) days in STROKESTOP and 90 (75-98)% and 8 (3-11) days in STROKESTOP II. Female sex and lower education were factors associated with both optimal adherence and adherence consistency in both studies. In STROKESTOP, low adherence and adherence consistency were associated with higher risk of adverse cerebral and cardiovascular outcomes (HR for composite primary endpoint 1.30 (1.11 to 1.51), p=0.001), including stroke (HR 1.68 (1.22 to 2.32), p=0.001) and dementia (1.67 (1.27 to 2.19), p<0.001).Conclusions Adherence to twice daily handheld ECG measurements in STROKESTOP was higher than to four times daily measurements in STROKESTOP II. Female sex and lower educational attainment were associated with >= 100% adherence and adherence consistency. Low adherence and adherence consistency were associated with a higher risk of adverse outcomes.
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  • van Deursen, Caroline J M, et al. (författare)
  • Vectorcardiographic QRS area as a novel predictor of response to cardiac resynchronization therapy.
  • 2015
  • Ingår i: Journal of electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 48:1, s. 45-52
  • Tidskriftsartikel (refereegranskat)abstract
    • QRS duration and left bundle branch block (LBBB) morphology are used to select patients for cardiac resynchronization therapy (CRT). We investigated whether the area of the QRS complex (QRSAREA) on the 3-dimensional vectorcardiogram (VCG) can improve patient selection.
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  • van Deursen, Caroline J M, et al. (författare)
  • Vectorcardiography for Optimization of Stimulation Intervals in Cardiac Resynchronization Therapy.
  • 2015
  • Ingår i: Journal of cardiovascular translational research. - : Springer Science and Business Media LLC. - 1937-5395 .- 1937-5387. ; 8:2, s. 128-137
  • Tidskriftsartikel (refereegranskat)abstract
    • Current optimization of atrioventricular (AV) and interventricular (VV) intervals in cardiac resynchronization therapy (CRT) is time consuming and subject to noise. We aimed to prove the principle that the best hemodynamic effect of CRT is achieved by cancelation of opposing electrical forces, detectable from the QRS morphology in the 3D vectorcardiogram (VCG). Different degrees of left (LV) and right ventricular (RV) pre-excitation were induced, using variation in AV intervals during LV pacing in 20 patients with left bundle branch block (LBBB) and variation in VV intervals during biventricular pacing in 18 patients with complete AV block or atrial fibrillation. The smallest QRS vector area identified stimulation intervals with minimal systolic stretch (median difference [IQR] 20ms [-20, 20ms] and maximal hemodynamic response (10ms [-20, 40ms]). Reliability of VCG measurements was superior to hemodynamic measurements. This study proves the principle that VCG analysis may allow easy and reliable optimization of stimulation intervals in CRT patients.
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  • Crijns, Harry J., et al. (författare)
  • Safe and effective conversion of persistent atrial fibrillation to sinus rhythm by intravenous AZD7009.
  • 2006
  • Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 3:11, s. 1321-1331
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Acute drug conversion of persistent atrial fibrillation usually fails. Objectives The purpose of this study was to test the proarrhythmic potential, safety, and efficacy of the novel antiarrhythmic agent AZD7009 in patients with persistent atrial fibrillation (AF) or atrial flutter (mean duration 43 days) scheduled for direct current (DC) cardioversion. Methods Patients were randomized to AZD7009 (3-hour intravenous infusion; n = 86) or placebo (n = 36). AZD7009 was given in doses intended to produce target pseudo–steady-state plasma levels of 0.25, 0.50, 0.75, 1.0, 1.5, 2.0, or 2.5 μmol/L after 30 minutes of infusion. DC cardioversion was performed if conversion to sinus rhythm (SR) did not occur within 2 hours of infusion. Results AZD7009 in a concentration-dependent manner increased the rate of conversion of AF to SR and shortened the time to conversion. At the three highest target concentrations of AZD7009, 45%, 64%, and 70% of AF patients converted after a mean time of 62, 55, and 26 minutes, respectively, whereas no placebo-treated patients converted. SR was maintained for 24 hours in 21 of 22 patients with drug-associated conversion. AZD7009 treatment was associated with QT-interval prolongation; the increase in QT corrected according to Fridericia typically ranged from 40 to 80 ms at targeted pseudo–steady-state plasma concentrations ≥0.75 μmol/L, but a number of outliers with QT corrected according to Fridericia >550 ms were seen in the higher concentration groups, particularly after conversion to SR and prolonged infusion. None of the patients exhibited torsades de pointes according to predefined criteria; however, one patient exhibited a nonsustained, polymorphic ventricular tachycardia of eight beats with torsades de pointes–like features after AZD7009 infusion (asymptomatic and discovered only upon retrospective Holter tape analysis). Clinical adverse events (primarily dizziness, bradycardia, hypotension, and nausea) were significantly more common in the highest target concentration AZD7009 group vs placebo (P <.001). Conclusion AZD7009 exhibited dose-dependent effects in converting AF to SR in AF patients and appeared to be associated with a low risk of proarrhythmia despite continued administration during a period of heightened vulnerability.
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  • Fabritz, Larissa, et al. (författare)
  • Dynamic risk assessment to improve quality of care in patients with atrial fibrillation : the 7th AFNET/EHRA Consensus Conference
  • 2021
  • Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 23:3, s. 329-344
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsThe risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes.Methods and resultsThis article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence.ConclusionThe remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.
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  • Køber, Lars, et al. (författare)
  • Increased mortality after dronedarone therapy for severe heart failure
  • 2008
  • Ingår i: The New England journal of medicine. - 1533-4406. ; 358:25, s. 2678-2687
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone, but it does not contain iodine and thus does not cause iodine-related adverse reactions. Therefore, it may be of value in the treatment of patients with heart failure. METHODS: In a multicenter study with a double-blind design, we planned to randomly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of dronedarone twice a day or placebo. The primary end point was the composite of death from any cause or hospitalization for heart failure. RESULTS: After inclusion of 627 patients (310 in the dronedarone group and 317 in the placebo group), the trial was prematurely terminated for safety reasons, at the recommendation of the data and safety monitoring board, in accordance with the board's predefined rules for termination of the study. During a median follow-up of 2 months, 25 patients in the dronedarone group (8.1%) and 12 patients in the placebo group (3.8%) died (hazard ratio in the dronedarone group, 2.13; 95% confidence interval [CI], 1.07 to 4.25; P=0.03). The excess mortality was predominantly related to worsening of heart failure--10 deaths in the dronedarone group and 2 in the placebo group. The primary end point did not differ significantly between the two groups; there were 53 events in the dronedarone group (17.1%) and 40 events in the placebo group (12.6%) (hazard ratio, 1.38; 95% CI, 0.92 to 2.09; P=0.12). More increases in the creatinine concentration were reported as serious adverse events in the dronedarone group than in the placebo group. CONCLUSIONS: In patients with severe heart failure and left ventricular systolic dysfunction, treatment with dronedarone was associated with increased early mortality related to the worsening of heart failure. (ClinicalTrials.gov number, NCT00543699.)
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  • Nieuwlaat, Robby, et al. (författare)
  • Antithrombotic treatment in real-life atrial fibrillation patients: a report from the Euro Heart Survey on Atrial Fibrillation
  • 2006
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 27:24, s. 3018-3026
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims To describe guideline adherence and application of different stroke risk strati. cation schemes regarding antithrombotic therapy in real-life atrial. brillation (AF) patients and to assess which factors influence antithrombotic management decisions. Methods and results The Euro Heart Survey enrolled 5333 AF patients in 35 countries, in 2003 and 2004. Prescription of antithrombotic drugs, especially oral anticoagulation (OAC), was hardly tailored to the patient's stroke risk pro. le as indicated by the joint guidelines of the American College of Cardiology, American Heart Association, and the European Society of Cardiology, ACCP guidelines, or CHADS(2) and Framingham risk scores. In multivariable analysis, only a limited number of the well-known stroke risk factors triggered OAC prescription. In contrast, less relevant factors, of which clinical type of AF and availability of an OAC monitoring outpatient clinic were the most marked, played a significant role in OAC prescription. Electrical cardioversions and catheter ablations clearly triggered OAC prescription, whereas pharmacological cardioversions even in the presence of stroke risk factors did not. Conclusion Antithrombotic therapy in AF is hardly tailored to the patient's stroke risk pro. le. Factors other than well-known stroke risk factors were significantly involved in antithrombotic management decisions. To facilitate this tailored treatment, guideline writers and physician educators should focus on providing one uniform and easy to use stroke risk strati. cation scheme.
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  • Nieuwlaat, Robby, et al. (författare)
  • Guideline-adherent antithrombotic treatment is associated with improved outcomes compared with undertreatment in high-risk patients with atrial fibrillation. The Euro Heart Survey on Atrial Fibrillation
  • 2007
  • Ingår i: American Heart Journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 153:6, s. 1006-1012
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Euro Heart Survey showed that antithrombotic treatment in patients with atrial fibrillation (AF) was moderately tailored to the 2001 American College of Cardiology, American Heart Association, and European Society of Cardiology (ACC/AHA/ESC) guidelines for the management of AF. What consequences does guideline-deviant antithrombotic treatment have in daily practice? Methods In the Euro Heart Survey on AF (2003-2004), an observational study on AF care in European cardiology practices, information was available on baseline stroke risk profile and antithrombotic drug treatment and on cardiovascular events during 1-year follow-up. Antithrombotic guideline adherence is assessed according to the 2001 ACC/AHA/ESC guidelines. Multivariable logistic regression was performed to assess the association of guideline deviance with adverse outcome. Results The effect of antithrombotic guideline deviance was analyzed exclusively in 3634 high-risk patients with AF because these composed the majority (89%) and because few cardiovascular events occurred in low-risk patients. Among high-risk patients, antithrombotic treatment was in agreement with the guidelines in 61% of patients, whereas 28% were undertreated and 11% overtreated. Compared to guideline adherence, undertreatment was associated with a higher chance of thromboembolism (odds ratio [OR], 1.97; 95% CI, 1.29-3.01; P = .004) and the combined end point of cardiovascular death, thromboembolism, or major bleeding (OR, 1.54; 95% CI, 1.14-2.10; P = .024). This increased risk was nonsignificant for the end point of stroke alone (OR, 1.42; 95% CI, 0.82-2.46; P = .170). Overtreatment was nonsignificantly associated with a higher risk for major bleeding (OR, 1.52; 95% CI, 0.76-3.02; P = .405). Conclusions Antithrombotic undertreatment of high-risk patients with AF was associated with a worse cardiovascular prognosis during 1 year, whereas overtreatment was not associated with a higher chance for major bleeding.
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  • Nieuwlaat, Robby, et al. (författare)
  • Should we abandon the common practice of withholding oral anticoagulation in paroxysmal atrial fibrillation?
  • 2008
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 29:7, s. 915-922
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims To assess the relation between the atrial fibrillation (AF) subtype and thrombo-embolic events. Methods and results The observational Euro Heart Survey on AF (2003-04) enrolled 1509 paroxysmal, 1109 persistent, and 1515 permanent AF patients, according to the 2001 American College of Cardiology, American Heart Association, and the European Society of Cardiology guidelines definitions. A 1 year follow-up was performed. Permanent AF patients had at baseline a worse stroke risk profile than paroxysmal and persistent AF patients. In paroxysmal AF, the risk for stroke, any thrombo-embolism, major bleeding and the combined endpoint of cardiovascular mortality, any thrombo-embolism, and major bleeding was comparable with persistent and permanent AF, in both univariable and multivariable analyses. Compared with AF patients without stroke, patients suffering from a stroke had a comparable frequency and duration of AF attacks, but tended to have a worse stroke risk profile at baseline. During 1 year following cardioversion, paroxysmal AF patients had a higher risk for stroke (P = 0.029) and any thrombo-embolism (P = 0.001) than persistent AF patients. Conclusion In the Euro Heart Survey, paroxysmal AF had a comparable risk for thrombo-embolic events as persistent and permanent AF. This observation strengthens the guideline recommendation not to consider the clinical AF subtype when deciding on anticoagulation.
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  • Simons, Sami O., et al. (författare)
  • Chronic obstructive pulmonary disease and atrial fibrillation an interdisciplinary perspective
  • 2021
  • Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 42:5
  • Forskningsöversikt (refereegranskat)abstract
    • Chronic obstructive pulmonary disease (COPD) is highly prevalent among patients with atrial fibrillation (AF), shares common risk factors, and adds to the overall morbidity and mortality in this population. Additionally, it may promote AF and impair treatment efficacy. The prevalence of COPD in AF patients is high and is estimated to be similar to 25%. Diagnosis and treatment of COPD in AF patients requires a close interdisciplinary collaboration between the electrophysiologist/cardiologist and pulmonologist. Differential diagnosis may be challenging, especially in elderly and smoking patients complaining of unspecific symptoms such as dyspnoea and fatigue. Routine evaluation of lung function and determination of natriuretic peptides and echocardiography may be reasonable to detect COPD and heart failure as contributing causes of dyspnoea. Acute exacerbation of COPD transiently increases AF risk due to hypoxia-mediated mechanisms, inflammation, increased use of beta-2 agonists, and autonomic changes. Observational data suggest that COPD promotes AF progression, increases AF recurrence after cardioversion, and reduces the efficacy of catheter-based antiarrhythmic therapy. However, it remains unclear whether treatment of COPD improves AF outcomes and which metric should be used to determine COPD severity and guide treatment in AF patients. Data from non-randomized studies suggest that COPD is associated with increased AF recurrence after electrical cardioversion and catheter ablation. Future prospective cohort studies in AF patients are needed to confirm the relationship between COPD and AF, the benefits of treatment of either COPD or AF in this population, and to clarify the need and cost-effectiveness of routine COPD screening.
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  • Thind, Munveer, et al. (författare)
  • Dronedarone treatment following cardioversion in patients with atrial fibrillation/flutter : A post hoc analysis of the EURIDIS and ADONIS trials
  • 2020
  • Ingår i: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1045-3873 .- 1540-8167. ; 31:5, s. 1022-1030
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The phase 3 EURIDIS and ADONIS studies evaluated dronedarone for atrial fibrillation (AF)/atrial flutter (AFL) recurrence in patients with nonpermanent AF. Here we assessed whether patient characteristics and/or treatment outcomes in these studies differed based on the need for cardioversion before randomization. Methods: Time to adjudicated first AF/AFL recurrence, symptomatic recurrence, cardiovascular hospitalization/death, and AF hospitalization, and safety were assessed by cardioversion status. Results: Of 1237 patients randomized (2:1 dronedarone:placebo), 364 required baseline cardioversion (dronedarone 243, placebo 121). Patients requiring cardioversion had a greater prevalence of cardiovascular comorbidities and shorter times to first AF/AFL recurrence compared with those not requiring cardioversion. Dronedarone was associated with longer median time to first AF/AFL recurrence vs placebo regardless of cardioversion status (cardioversion: 50 vs 15 days, hazard ratio [HR] 0.76; 95% confidence interval [CI], 0.59-0.97; P =.02; non-cardioversion: 150 vs 77 days, HR 0.76; 95% CI, 0.64-0.90; P <.01). Dronedarone was similarly associated with prolonged median time to symptomatic recurrence vs placebo in the cardioversion (347 vs 87 days, HR 0.65; 95% CI, 0.49-0.87) and non-cardioversion (288 vs 120 days, HR 0.74; 95% CI, 0.62-0.90) populations. Risk of cardiovascular hospitalization/death and first AF hospitalization was lower with dronedarone vs placebo regardless of cardioversion status, but differences were not statistically significant. The safety of dronedarone was similar in both groups. Conclusion: Patients requiring baseline cardioversion represent a distinct population, having more underlying cardiovascular disease and experiencing a shorter time to AF/AFL recurrences. Dronedarone was associated with improved efficacy vs placebo regardless of cardioversion status.
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27.
  • Thind, Munveer, et al. (författare)
  • Efficacy and safety of dronedarone versus placebo in patients with atrial fibrillation stratified according to renal function : Post hoc analyses of the EURIDIS-ADONIS trials
  • 2022
  • Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 45:1, s. 101-109
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The use of antiarrhythmic drugs (AADs) in patients with chronic kidney disease (CKD) is complex because impaired renal clearance can cause increased drug levels, and risk of intolerance or adverse events. Due to the propensity for CKD to occur alongside atrial fibrillation/atrial flutter (AF/AFL), it is essential that AAD safety and efficacy are assessed for patients with CKD. Hypothesis: Dronedarone, an approved AAD, may present a suitable therapeutic option for patients with AF/AFL and concomitant CKD. Methods: EURIDIS-ADONIS (EURIDIS, NCT00259428; ADONIS, NCT00259376) were identically designed, multicenter, double-blind, parallel-group trials investigating AF/AFL control with dronedarone 400 mg twice daily versus placebo (randomized 2:1). In this post hoc analysis, the primary endpoint was time to first AF/AFL. Patients were stratified according to renal function using the CKD-Epidemiology Collaboration equation and divided into estimated glomerular filtration rate (eGFR) subgroups of 30–44, 45–59, 60–89, and ≥90 ml/min. Time-to-events between treatment groups were compared using log-rank testing and Cox regression. Results: At baseline, most (86%) patients demonstrated a mild or mild-to-moderate eGFR decrease. Median time to first AF/AFL recurrence was significantly longer with dronedarone versus placebo for all eGFR subgroups except the 30 to 44 ml/min group, where the trend was similar but statistical power may have been limited by the small population. eGFR stratification had no significant effect on serious adverse events, deaths, or treatment discontinuations. Conclusions: This analysis suggests that dronedarone could be an effective therapeutic option for AF with an acceptable safety profile in patients with impaired renal function.
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28.
  • Tilz, Roland Richard, et al. (författare)
  • Which patients with atrial fibrillation undergo an ablation procedure today in Europe? : A report from the ESC-EHRA-EORP Atrial Fibrillation Ablation Long-Term and Atrial Fibrillation General Pilot Registries
  • 2020
  • Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 22:2, s. 250-258
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsRhythm control management in patients with atrial fibrillation (AF) may be unequal across Europe. The aim of this study was to investigate how selective the patient cohort referred for AF ablation is, as compared to the general AF population in Europe, and to describe the governing mechanisms for such selection.Methods and resultsDescriptive comparative statistical analyses of the baseline characteristics were performed between the cohorts of Atrial Fibrillation Ablation Long-Term (ESC EORP AFA-LT) registry, designed to provide a picture of contemporary real-world AF ablation, and the AF population from the AF-General (ESC EORP AF-Gen) pilot registry. Data collection was performed using a web-based system. In the AFA and in the Atrial Fibrillation General (AFG) pilot registries, 3593 and 3049 patients were enrolled, respectively. Patients who underwent AF ablation were younger, more commonly male, and had significantly less comorbidities. Atrial Fibrillation Ablation patients often presented without comorbidities, resulting in a lower risk of stroke (CHA2DS2-VASc ≥5: 2.9% vs. 24.5%, all P < 0.001) and bleeding (HAS-BLED ≥2: 8.5% vs. 40.5%, P < 0.001) but with European Heart Rhythm Association (EHRA) scores >1 and more prevalent AF-related symptoms such as palpitations, fatigue, and weakness (all P < 0.001) as compared to the general AF patients. Atrial Fibrillation Ablation patients were significantly more often male, had higher left ventricular ejection fraction (59.5% vs. 52.4%) and smaller left atrial size on echocardiogram (P < 0.001 each).ConclusionThe comparison of the patient cohorts in the AFA and AFG registries showed that AF ablation in European clinical practice is mostly performed in relatively young, symptomatic and relatively healthy patients.
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29.
  • Vaduganathan, Muthiah, et al. (författare)
  • Dronedarone for the treatment of atrial fibrillation with concomitant heart failure with preserved and mildly reduced ejection fraction : a post-hoc analysis of the ATHENA trial
  • 2022
  • Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:6, s. 1094-1101
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Limited therapeutic options are available for the management of atrial fibrillation/flutter (AF/AFL) with concomitant heart failure (HF) with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF). Dronedarone reduces the risk of cardiovascular events in patients with AF, but sparse data are available examining its role in patients with AF complicated by HFpEF and HFmrEF. Methods and results: ATHENA was an international, multicentre trial that randomized 4628 patients with paroxysmal or persistent AF/AFL and cardiovascular risk factors to dronedarone 400 mg twice daily versus placebo. We evaluated patients with (i) symptomatic HFpEF and HFmrEF (defined as left ventricular ejection fraction [LVEF] >40%, evidence of structural heart disease, and New York Heart Association class II/III or diuretic use), (ii) HF with reduced ejection fraction (HFrEF) or left ventricular dysfunction (LVEF ≤40%), and (iii) those without HF. We assessed effects of dronedarone versus placebo on death or cardiovascular hospitalization (primary endpoint), other key efficacy endpoints, and safety. Overall, 534 (12%) had HFpEF or HFmrEF, 422 (9%) had HFrEF or left ventricular dysfunction, and 3672 (79%) did not have HF. Patients with HFpEF and HFmrEF had a mean age of 73 ± 9 years, 37% were women, and had a mean LVEF of 57 ± 9%. Over a mean follow-up of 21 ± 5 months, dronedarone consistently reduced risk of death or cardiovascular hospitalization (hazard ratio 0.76; 95% confidence interval 0.69–0.84) without heterogeneity based on HF status (pinteraction >0.10). This risk reduction in the primary endpoint was consistent across the range of LVEF (as a continuous function) in HF without heterogeneity (pinteraction = 0.71). Rates of death, cardiovascular hospitalization, and HF hospitalization each directionally favoured dronedarone versus placebo in HFpEF and HFmrEF, but these treatment effects were not statistically significant in this subgroup. Conclusions: Dronedarone is associated with reduced cardiovascular events in patients with paroxysmal or persistent AF/AFL and HF across the spectrum of LVEF, including among those with HFpEF and HFmrEF. These data support a rationale for a future dedicated and powered clinical trial to affirm the net clinical benefit of dronedarone in this population.
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30.
  • van Rosmalen, Frank, et al. (författare)
  • Adenosine usage during AF ablation in Europe and selected long-term findings from the ESC-EHRA EORP Atrial Fibrillation Ablation Long-Term registry.
  • 2021
  • Ingår i: Journal of Interventional Cardiac Electrophysiology. - : Springer Science and Business Media LLC. - 1383-875X .- 1572-8595. ; 60, s. 395-406
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Adenosine can be used to reveal dormant pulmonary vein (PV) conduction after PV isolation (PVI). This study presents a subanalysis of real-world 1-year follow-up data from the ESC-EHRA EORP Atrial Fibrillation (AF) Ablation Long-Term registry to analyze the usage of adenosine during PVI treatment in terms of rhythm outcome and safety.METHODS: The registry consists of 104 participating centers in 27 countries within the European Society of Cardiology. The registry data was split into an adenosine group (AG) and no-adenosine group (NAG). Procedure characteristics and patient outcome were compared.RESULTS: Adenosine was administered in 10.8% of the 3591 PVI patients included in the registry. Spain, the Netherlands, and Italy included the majority of adenosine cases (48.8%). Adenosine was applied more often in combination with open irrigation radiofrequency (RF) energy (74.7%) and less often in combination with nonirrigated RF energy (1.6%). After 1 year, a higher percentage of the AG was free from AF compared with the NAG (68.9% vs 59.1%, p < 0.001). Adenosine was associated with better rhythm outcome in RF ablation procedures, but not in cryo-ablation procedures (freedom from AF: RF: AG: 70.9%, NAG: 58.1%, p < 0.001, cryo: AG: 63.9%, NAG: 63.8%, p = 0.991).CONCLUSIONS: The use of adenosine was associated with a better rhythm outcome after 1 year follow-up and seems more useful in patients treated with RF energy compared with patients treated with cryo energy. Given the improved rhythm outcome at 1-year follow-up, it seems reasonable to encourage the use of adenosine during RF AF ablation.
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