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Atrial fibrillation: inflammatory and pharmacological studies
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro universitet , 2012. , 75 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 70
Keyword [en]
Atrial fibrillation, inflammation, randomised, sudden cardiac
National Category
Medical and Health Sciences Cardiac and Cardiovascular Systems
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-22590ISBN: 978-91-7668-875-5 (print)OAI: oai:DiVA.org:oru-22590DiVA: diva2:516677
Public defence
2012-06-15, Wilandersalen, Universitetssjukhuset, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2012-04-19 Created: 2012-04-19 Last updated: 2017-10-17Bibliographically approved
List of papers
1. Source of inflammatory markers in patients with atrial fibrillation
Open this publication in new window or tab >>Source of inflammatory markers in patients with atrial fibrillation
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2008 (English)In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 10, 848-853 p.Article in journal (Refereed) Published
Abstract [en]

Aims Elevated levels of C-reactive protein and other inflammatory markers have been reported in some patients with atrial fibrillation (AF). Whether this finding is related to AF per se or to other conditions remains unclear. In addition, the source of inflammatory markers is unknown. Therefore, in the present study, we sought to assess the extent and the source of inflammation in patients with AF and no other concomitant heart or inflammatory conditions.

Methods and results The study group consisted of 29 patients referred for radiofrequency catheter ablation: 10 patients with paroxysmal AF, 8 patients with permanent AF, and 10 control patients with Wolf-Parkinson-White (WPW) syndrome and no evidence of AF (mean age 54±11 vs. 57±13 vs. 43±16). No patient had structural heart diseases or inflammatory conditions. High-sensitive C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were assessed in blood samples from the femoral vein, right atrium, coronary sinus, and the left and right upper pulmonary veins. All samples were collected before ablation. Compared with controls and patients with paroxysmal AF, patients with permanent AF had higher plasma levels of IL-8 in the samples from the femoral vein, right atrium, and coronary sinus, but not in the samples from the pulmonary veins (median values in the femoral vein: 2.58 vs. 2.97 vs. 4.66 pg/mL, P = 0.003; right atrium: 2.30 vs. 3.06 vs. 3.93 pg/mL, P = 0.013; coronary sinus: 2.85 vs. 3.15 vs. 4.07, P = 0.016). A high-degree correlation existed between the IL-8 levels in these samples (correlation coefficient between 0.929 and 0.976, P< 0.05). No differences in the C-reactive protein and IL-6 levels were noted between the three groups of patients.

Conclusion The normal levels of C-reactive protein and IL-6, alongwith the elevated levels of IL-8 in patients with permanent AF but not in those with paroxysmal AF, suggest a link between a low-grade inflammatory reaction and long-lasting AF. The elevated IL-8 levels in the peripheral blood, right atrium, and coronary sinus but not in the pulmonary veins suggest a possible source of inflammation in the systemic circulation.

Place, publisher, year, edition, pages
Oxford University Press, 2008
Keyword
Atrial fibrillation, Inflammation, Catheter ablation
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-22941 (URN)10.1093/europace/eun111 (DOI)
Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2017-12-07Bibliographically approved
2. Atorvastatin and persistent atrial fibrillation following cardioversion: a randomized placebo-controlled multicentre study
Open this publication in new window or tab >>Atorvastatin and persistent atrial fibrillation following cardioversion: a randomized placebo-controlled multicentre study
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2009 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 30, no 7, 827-833 p.Article in journal (Refereed) Published
Abstract [en]

AIMS: To evaluate the effect of atorvastatin in achieving stable sinus rhythm (SR) 30 days after electrical cardioversion (CV) in patients with persistent atrial fibrillation (AF). METHODS AND RESULTS: The study included 234 patients. The patients were randomized to treatment with atorvastatin 80 mg daily (n = 118) or placebo (n = 116) in a prospective, double-blinded fashion. Treatment was initiated 14 days before CV and was continued 30 days after CV. The two groups were well-balanced with respect to baseline characteristics. Mean age was 65 +/- 10 years, 76% of the patients were male and 4% had ischaemic heart disease. Study medication was well-tolerated in all patients but one. Before primary endpoint 12 patients were excluded. In the atorvastatin group 99 patients (89%) converted to SR at electrical CV compared with 95 (86%) in the placebo group (P = 0.42). An intention-to-treat analysis with the available data, by randomization group, showed that 57 (51%) in the atorvastatin group and 47 (42%) in the placebo group were in SR 30 days after CV (OR 1.44, 95%CI 0.85-2.44, P = 0.18). CONCLUSION: Atorvastatin was not statistically superior to placebo with regards to maintaining SR 30 days after CV in patients with persistent AF.

Place, publisher, year, edition, pages
Philadelphia: W.B. Saunders, 2009
National Category
Medical and Health Sciences Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:oru:diva-11644 (URN)10.1093/eurheartj/ehp006 (DOI)19202157 (PubMedID)
Available from: 2010-08-27 Created: 2010-08-27 Last updated: 2017-12-12Bibliographically approved
3. The safety of flecainide treatment of atrial fibrillation: long-term incidence of sudden cardiac death and proarrhythmic events
Open this publication in new window or tab >>The safety of flecainide treatment of atrial fibrillation: long-term incidence of sudden cardiac death and proarrhythmic events
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2011 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 3, 281-290 p.Article in journal (Refereed) Published
Abstract [en]

Objective.To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) andproarrhythmic events.

Design.Retrospective,observational cohort study.Setting.Single-centre study at Örebro University Hospital, Sweden.

Subjects.A total of 112 patients with paroxysmal (51%) or persistent (49%) AF (mean age 60 ± 11 years) were included after identifying all patients with AF who initiated oral flecainide treatment (mean dose 203 ± 43 mg per day) between 1998 and 2006. Standard exclusion⁄inclusion criteria for flecainide were used,andflecainidetreatmentwasusually combined withanatrioventricular-blocking agent (89%).Main outcome measure.Death was classified as sudden or nonsudden according to standard definitions. Proarrhythmia was defined as cardiac syncope or lifethreatening arrhythmia.

Results.Eight deaths were reported during a mean follow- up of 3.4 ± .4 years. Compared to the general population, the standardized mortality ratios were 1.57 (95% confidence interval (CI) 0.68–3.09) for allcause mortality and 4.16 (95% CI 1.53–9.06) for death from cardiovascular disease. Three deaths were classified as SCDs. Proarrhythmic events occurred in six patients (two each with wide QRS tachycardia, 1 : 1 conducted atrial flutter and syncope during exercise).

Conclusion.We found an increased incidence of SCD or proarrhythmic events in this real-world study of flecainide used for the treatment of AF. The findings suggest that further investigation into the safety of flecainide for the treatment of patients with AF is warranted.

Place, publisher, year, edition, pages
John Wiley & Sons, 2011
Keyword
atrialfibrillation, flecainide, proarrhythmia, safety, suddencardiac death
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-22942 (URN)10.1111/j.1365-2796.2011.02395.x (DOI)
Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2017-12-07Bibliographically approved
4. Safety of flecainide for atrial fibrillation: the Swedish atrial fibrillation cohort study
Open this publication in new window or tab >>Safety of flecainide for atrial fibrillation: the Swedish atrial fibrillation cohort study
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background Little is known about the safety of flecainide in atrial fibrillation (AF). Whether current flecainide treatment practice in Sweden is associated with increased mortality compared to treatment with beta-blockers alone was investigated in patients with atrial fibrillation (AF).

Methods and Results A total of 182,678 patients diagnosed with AF between 1 July 2005 and 31 December 2008 were identified through the Swedish National Hospital Discharge Register. These data were matched to data from the Prescribed Drug Register and information about death from the Total Population Register. The primary outcome was all cause mortality at the end of the study period, 1 Feb 2010. Flecainide was prescribed to 5381 patients (2.9%), and 64,918 patients (45.7%) received beta-blockers only. During follow-up, 2.8% and 30.8% of these patients died, respectively. After coarsened and exact matching, 2,178 patients (1.2% of total) on flecainide and beta-blockers had more similar baseline characteristics to 27,313 patients (15.3% of total) on beta-blockers only. In the main analysis, flecainide exposure was not associated with increased mortality (OR 0.27, 95% CI 0.21-0.36,P<0.001). In the matched flecainide population, 205 (9.4%) patients had underlying structural heart disease. Sixteen (28.6%) of the flecainide-exposed patients who died had structural heart disease. The patients who only received flecainide (n=264) had higher mortality rate than the patients who received flecainide and beta-blockers (6.8 versus 2.6%,P<0.001).

Conclusions Flecainide is not associated with increased mortality in patients with AF compared to beta-blockers alone. Patients who die after receiving flecainide often have structural heart disease.

National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-22943 (URN)
Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2017-10-17Bibliographically approved

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