Fibrosis, Inflammation and Brain Health in Atrial Fibrillation.

Fibrosis, Inflammation and Brain Health in Atrial Fibrillation. The Norwegian Atrial Fibrillation and Stroke Study

Protocol synopsis Sponsor: Oslo University Hospital Title: Fibrosis, inflammation and cerebral infarction in patients with atrial fibrillation Study Design: The study is an observational prospective study of atrial fibrillation patients undergoing direct-current cardioversion.

Primary Objective: To assess the prevalence and causes of new silent cerebral ischemic lesions after programmed direct-current cardioversion using diffusion-weighted sequences in brain MRI (DWMRI).

Secondary Objectives:

To study the impact of inflammation measured by biomarkers and cardiac 18F-FDG-PET on the risk for new silent cerebral ischemic lesions after direct-current cardioversion for AF.

To assess the impact of fibrosis measured by biomarkers on the risk for new silent cerebral ischemic lesions after direct-current cardioversion for AF.

To assess cognitive and cerebral structural and metabolic changes after direct-current cardioversion for AF using cognitive assessments and cerebral and cardiac 18F-FDG-PET before and 12 months after treatment.

Number of Subjects: 50

Study Centers: Østfold Hospital Trust

Duration of Study Participation:

• Enrollment: 18 months
• Follow-up period: 12 months
• Total Study Duration: 30 months

Primary Endpoints:

• Number of new small cerebral infarcts detected with DWMRI two weeks after direct current cardioversion.

Secondary Endpoints:

• Rate of AF recurrence within 1 year after direct current cardioversion
• Change in levels of inflammation biomarkersfrom baseline to 12 months follow-up
• Change in levels of fibrosis biomarkers from baseline to 12 months follow-up
• Cognitive function at 12 months follow-up
• Changes in uptake pattern on cerebral 18F-FDG-PET from baseline to 12 months follow-up
• Changes in uptake pattern on cardiac 18F-FDG-PET from baseline to 12 months follow-up
• Brain volume at 12 months follow-up
• White matter volume 12 months follow-up
• Grey matter volume 12 months follow-up
• Cortical volume 12 months follow-up
• RSI-derived diffusion parameters 12 months follow-up: fast apparent diffusion coefficient, extracellular water fraction, fractional anisotropy; free water fraction; intracranial volume; NAWM: normal appearing white matter; neurite density; RSI: restriction spectrum imaging; sADC: slow apparent diffusion coefficient;restricted fractional anisotropy; white matter lesions.

1. Known atrial fibrillation
2. Age <80 years
3. CHA2DS2-VASc ≤ 4
4. Planned direct-current cardioversion

Exclusion criteria:

1. CHA2DS2-VASc >4
2. Life expectancy less than 1 year
3. Patient otherwise not eligible for the study or adherent for follow-up (eg nonresident) or has concurrent disease affecting outcome (e.g. multiple sclerosis, cancer)