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Atrial fibrillation: treatment, associated conditions and quantification of symptoms
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. There is a need for new pharmacological treatment strategies since the current antiarrhythmic drugs have a modest efficacy and may have severe side effects. Cardioversion (CV) of AF offers an opportunity to study related conditions in sinus rhythm (SR) and during AF. Since catheter ablation of AF is a symptomatic treatment, it is important to have tools for measurement of arrhythmia-related symptoms. Aims: To evaluate the effect of atorvastatin on maintaining SR after CV of persistent AF. To assess if highsensitivity C-reactive protein (hsCRP) predicts the recurrence of AF after CV in a population randomized to treatment with either atorvastatin or placebo. To quantify the symptomatic effect of left atrial catheter ablation of AF. To assess if the restoration of SR by CV, in a population with persistent AF, affects sleep apnea. Methods: Paper I: A total of 234 patients were randomized to treatment with either high dose atorvastatin or placebo prior to CV. Paper II: In a pre-specified substudy which included 128 of the patients in study I, hsCRP was analyzed before and after CV. Paper III: Umea 22 Arrhythmia Questions (U22) is a questionnaire that quantifies paroxysmal tachycardia symptoms. A total of 105 patients underwent first-time pulmonary vein isolation and answered U22 forms at baseline and follow-up 304 (SD 121) days after ablation. Paper IV: Polysomnography was performed before and after CV in 23 patients with persistent AF scheduled for elective CV. Results: Paper I: 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). Paper II: HsCRP did not significantly predict recurrence of AF at 30 days. However, after adjusting for treatment with atorvastatin, hsCRP predicted the recurrence of AF (OR 1.14, 95% CI 1.01–1.27). Six months after CV, hsCRP at randomization predicted recurrence of AF in both univariate analysis (OR 1.30, 95% CI 1.06–1.60) and in multivariate logistic regression analysis (OR 1.33, 95% CI 1.06– 1.67). Paper III: The U22 scores for well-being, arrhythmia as cause for impaired well-being, derived timeaspect score for arrhythmia, and discomfort during attack detected relevant improvements of symptoms after the ablation. U22 showed larger improvement in patients undergoing only one procedure than in patients who later underwent repeated interventions. Paper IV: Obstructive sleep apnea occurred in 17/23 patients (74%), and central sleep apnea in 6/23 patients (26%). Five patients had both obstructive and central sleep apnea. SR at follow-up was achieved in 16 patients. The obstructive apnea-hypopnea index, central apneahypopnea index, and the number of patients with obstructive or central sleep apnea did not differ before and after restoration of SR. Conclusions: Atorvastatin is not a treatment option with regards to maintaining SR after CV in patients with persistent AF. HsCRP was associated with AF recurrence 1 and 6 months after successful CV of persistent AF. U22 quantifies the symptomatic improvement after AF ablation with adequate internal consistency and construct validity. Both obstructive and central sleep apneas are highly prevalent in patients with persistent AF. Obstructive sleep apneas are unaffected by the CV of AF to SR.

Place, publisher, year, edition, pages
Umeå: Umeå University , 2017. , p. 64
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1902
Keywords [en]
Atrial fibrillation, cardioversion, atorvastatin, high-sensitivity C-reactive protein, symptoms, sleep apnea
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
URN: urn:nbn:se:umu:diva-138378ISBN: 978-91-7601-742-5 (print)OAI: oai:DiVA.org:umu-138378DiVA, id: diva2:1134813
Public defence
2017-09-15, Hörsal E04, Biomedicinhuset, Norrlands universitetssjukhus, Umeå, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2017-08-25 Created: 2017-08-21 Last updated: 2018-06-09Bibliographically approved
List of papers
1. 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, p. 827-833Article 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.

Keywords
Atrial fibrillation, Randomized, Cardioversion, Trials, Placebo-controlled, Lipids
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-32456 (URN)10.1093/eurheartj/ehp006 (DOI)000264889600018 ()19202157 (PubMedID)
Available from: 2010-03-11 Created: 2010-03-11 Last updated: 2018-06-08Bibliographically approved
2. The predictive value of C-reactive protein on recurrence of atrial fibrillation after cardioversion with or without treatment with atorvastatin
Open this publication in new window or tab >>The predictive value of C-reactive protein on recurrence of atrial fibrillation after cardioversion with or without treatment with atorvastatin
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2013 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 167, no 5, p. 2088-2091Article in journal (Refereed) Published
Abstract [en]

Background: The aim of this study was to investigate whether high-sensitivity C-reactive protein (hsCRP) levels prior to cardioversion (CV) predict recurrence of atrial fibrillation (AF) in patients randomized to treatment with either atorvastatin or placebo 30 and 180 days after CV. Methods: This was a prespecified substudy of 128 patients with persistent AF randomized to treatment with atorvastatin 80 mg/day or placebo, initiated 14 days before CV, and continued 30 days after CV. HsCRP levels were measured at randomization, at the time of CV, and 2 days and 30 days after CV. Results: In univariate analysis of those who were in sinus rhythm 2 h after CV, hsCRP did not significantly (odds ratio [OR] 1.11, 95% confidence interval [CI] 0.99-1.25) predict recurrence of AF at 30 days. However, after adjusting for treatment with atorvastatin, hsCRP predicted the recurrence of AF (OR 1.14, 95% CI 1.01-1.27). In a multivariate logistic regression analysis with gender, age, body mass index (BMI), smoking, cholesterol, and treatment with atorvastatin as covariates, the association was still significant (OR 1.14, 95% CI 1.01-1.29). Six months after CV, hsCRP at randomization predicted recurrence of AF in both univariate analysis (OR 1.30, 95% CI 1.06-1.60) and in multivariate logistic regression analysis (OR 1.33, 95% CI 1.06-1.67). Conclusion: HsCRP was associated with AF recurrence one and six months after successful CV of persistent AF. However, the association at one month was significant only after adjusting for atorvastatin treatment.

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
Atorvastatin, Atrial fibrillation, Cardioversion, C-reactive protein
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-80745 (URN)10.1016/j.ijcard.2012.05.071 (DOI)000323569600075 ()22704860 (PubMedID)
Available from: 2013-10-07 Created: 2013-09-25 Last updated: 2019-11-27Bibliographically approved
3. U22 protocol as measure of symptomatic improvement after catheter ablation of atrial fibrillation
Open this publication in new window or tab >>U22 protocol as measure of symptomatic improvement after catheter ablation of atrial fibrillation
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2013 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 4, p. 240-246Article in journal (Refereed) Published
Abstract [en]

Introduction. Left atrial catheter ablation is useful as symptomatic treatment in selected patients with atrial fibrillation (AF). Evaluation requires measurement of arrhythmia-related symptoms. Many of the published protocols have drawbacks and have been used in AF only, with no possible comparison to other ablations that compete for the same resources. U22 is a published protocol that quantifies paroxysmal tachycardia symptoms through scales with 11 answer alternatives, translated into discrete numerical scales 0-10. It has been shown to reflect the clinical improvement after ablation of supraventricular tachycardia. Here we report the use of U22 in measuring improvement after catheter ablation for AF. Material and methods. A total of 105 patients underwent first-time ablation for AF and answered U22 and SF-36 forms at baseline and follow-up 304 (SD 121) days after ablation. Independently, the patients underwent a clinical follow-up. All decisions regarding medication and reablation were taken without knowledge of the symptom scores. Results. The U22 scores for well-being, arrhythmia as cause for impaired well-being, derived time-aspect score for arrhythmia, and discomfort during attack detected relevant improvements of symptoms after the ablation. U22 showed larger improvement in patients undergoing only one procedure than in patients who later underwent repeated interventions, thus reflecting the independent clinical decision for reablation. Conclusion. U22 quantifies the symptomatic improvement after AF ablation with adequate internal consistency and construct validity. U22 mirrors aspects of the arrhythmia symptomatology other than SF-36.

Place, publisher, year, edition, pages
Informa Healthcare, 2013
Keywords
Arrhythmia symptoms, atrial fibrillation, catheter ablation, quality of life, symptom-specific protocol
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-82806 (URN)10.3109/03009734.2013.821190 (DOI)000325527300006 ()
Available from: 2013-11-11 Created: 2013-11-11 Last updated: 2018-06-08Bibliographically approved
4. Cardioversion of atrial fibrillation does not affect obstructive sleep apnea
Open this publication in new window or tab >>Cardioversion of atrial fibrillation does not affect obstructive sleep apnea
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2017 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 2, p. 114-118Article in journal (Refereed) Published
Abstract [en]

Background: Sleep apnea is common in patients with atrial fibrillation, but the effect of the cardioversion of atrial fibrillation to sinus rhythm on central and obstructive apneas is mainly unknown. The primary aim of the study was to analyze the association between cardioversion of atrial fibrillation and sleep apneas, to investigate whether obstructive or central sleep apneas are reduced following cardioversion. A secondary objective was to study the effect on sleep quality. Methods: Twenty-three patients with atrial fibrillation were investigated using overnight polysomnography, including esophagus pressure monitoring and ECG, before and after the cardioversion of persistent atrial fibrillation. Results: Obstructive sleep apnea occurred in 17/23 patients (74%), and central sleep apnea in 6/23 patients (26%). Five patients had both obstructive and central sleep apnea. Sinus rhythm at follow-up was achieved in 16 patients. The obstructive apnea-hypopnea index, central apnea-hypopnea index, and the number of patients with obstructive or central sleep apnea did not differ before and after restoration of sinus rhythm. Sleep time, sleep efficiency, time in different sleep stages, and subjective daytime sleepiness were normal and unaffected by cardioversion. Conclusions: Both obstructive and central sleep apneas are highly prevalent in patients with persistent atrial fibrillation. Obstructive sleep apneas are unaffected by the cardioversion of atrial fibrillation to sinus rhythm. The sleep pattern is normal and unaffected by cardioversion in patients with atrial fibrillation. Clinical Trial Registration: Trial number NCT00429884.

Place, publisher, year, edition, pages
Taylor & Francis, 2017
Keywords
Atrial fibrillation, cardioversion, polysomnography, sleep apnea
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-135990 (URN)10.1080/03009734.2017.1291545 (DOI)000401756500007 ()28291376 (PubMedID)
Available from: 2017-06-13 Created: 2017-06-13 Last updated: 2019-05-20Bibliographically approved

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