| 1. |
- Spronk, H. M. H., et al.
(författare)
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Atherothrombosis and Thromboembolism : Position Paper from the Second Maastricht Consensus Conference on Thrombosis
- 2018
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Ingår i: Thrombosis and Haemostasis. - : SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN. - 0340-6245 .- 2567-689X. ; 118:2, s. 229-250
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Forskningsöversikt (refereegranskat)abstract
- Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics:1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in) stability; proteomic and metabolomics data are to be added to genetic information.2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; diseasemechanism-based biomarkers need to be identified; experimental systems are needed that incorporatewhole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation.3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin-angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet-fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences.4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis a vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time.5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novelmodified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor.
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| 2. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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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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| 3. |
- d'Alessandro, Elisa, et al.
(författare)
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Thrombo-Inflammation in Cardiovascular Disease : An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis
- 2020
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 120:4, s. 538-564
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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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| 4. |
- De Ferrari, G. M., et al.
(författare)
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Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure
- 2011
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 32:7, s. 847-855
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: In chronic heart failure (CHF), reduced vagal activity correlates with increased mortality and acute decompensation. Experimentally, chronic vagus nerve stimulation (VNS) improved left ventricular (LV) function and survival; clinically, it is used for the treatment of drug-refractory epilepsy. We assessed safety and tolerability of chronic VNS in symptomatic CHF patients, using a novel implantable nerve stimulation system. The secondary goal was to obtain preliminary data on clinical efficacy. METHODS AND RESULTS: This multi-centre, open-label phase II, two-staged study (8-patient feasibility phase plus 24-patient safety and tolerability phase) enrolled 32 New York Heart Association (NYHA) class II-IV patients [age 56 +/- 11 years, LV ejection fraction (LVEF) 23 +/- 8%]. Right cervical VNS with CardioFit (BioControl Medical) implantable system started 2-4 weeks after implant, slowly raising intensity; patients were followed 3 and 6 months thereafter with optional 1-year follow-up. Overall, 26 serious adverse events (SAEs) occurred in 13 of 32 patients (40.6%), including three deaths and two clearly device-related AEs (post-operative pulmonary oedema, need of surgical revision). Expected non-serious device-related AEs (cough, dysphonia, and stimulation-related pain) occurred early but were reduced and disappeared after stimulation intensity adjustment. There were significant improvements (P < 0.001) in NYHA class quality of life, 6-minute walk test (from 411 +/- 76 to 471 +/- 111 m), LVEF (from 22 +/- 7 to 29 +/- 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year. CONCLUSIONS: This open-label study shows that chronic VNS in CHF patients with severe systolic dysfunction may be safe and tolerable and may improve quality of life and LV function. A controlled clinical trial appears warranted.
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| 5. |
- Nieuwlaat, R, et al.
(författare)
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Atrial fibrillation management: a prospective survey in ESC Member Countries - The Euro Heart Survey on Atrial Fibrillation
- 2005
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 26:22, s. 2422-2434
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Tidskriftsartikel (refereegranskat)abstract
- Aims To describe atrial fibrillation (AF) management in member countries of the European Society of Cardiology (ESC) and to verify cardiology practices against guidelines. Methods and results Among 182 hospitals in 35 countries, 5333 ambulant and hospitalized AF patients were enrolled, in 2003 and 2004. AF was primary or secondary diagnosis, and was confirmed on ECG in the preceding 12 months. Clinical type of AF was reported to be first detected in 978, paroxysmal in 1517, persistent in 1167, and permanent in 1547 patients. Concomitant diseases were present in 90% of all patients, causing risk factors for stroke to be also highly prevalent (86%). As many as 69% of patients were symptomatic at the time of the survey; among asymptomatic patients, 54% were previously experienced symptoms. Oral anticoagulation was prescribed in 67 and 49% of eligible and ineligible patients, respectively. A rhythm control strategy was applied in 67% of currently symptomatic patients and in 44% of patients who never experienced symptoms. Conclusion This survey provides a unique snapshot of current AF management in ESC member countries. Discordance between guidelines and practice was found regarding several issues on stroke prevention and antiarrhythmic therapy.
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| 6. |
- Schnabel, Renate B., et al.
(författare)
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Searching for Atrial Fibrillation Poststroke : A White Paper of the AF-SCREEN International Collaboration
- 2019
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Ingår i: Circulation. - 1524-4539. ; 140:22, s. 1834-1850
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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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| 7. |
- van Deursen, Caroline J M, et al.
(författare)
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Vectorcardiography for Optimization of Stimulation Intervals in Cardiac Resynchronization Therapy.
- 2015
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Ingår i: Journal of cardiovascular translational research. - : Springer Science and Business Media LLC. - 1937-5395 .- 1937-5387. ; 8:2, s. 128-137
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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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| 8. |
- Hendriks, Jeroen, et al.
(författare)
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Integrated specialized atrial fibrillation clinics reduce all-cause mortality: post hoc analysis of a randomized clinical trial
- 2019
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Ingår i: Europace. - : OXFORD UNIV PRESS. - 1099-5129 .- 1532-2092. ; 21:12, s. 1785-1792
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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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| 9. |
- Kowey, Peter R, et al.
(författare)
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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
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 124:24, s. 2649-2660
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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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| 10. |
- Nieuwlaat, Robby, et al.
(författare)
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Antithrombotic treatment in real-life atrial fibrillation patients: a report from the Euro Heart Survey on Atrial Fibrillation
- 2006
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 27:24, s. 3018-3026
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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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