Atrial fibrillation (AF) is the most common sustained arrhythmia and the number of patients with AF is expected to increase substantially in the coming decades. One third of patients with AF report no AF-associated symptoms, but up to one-fourth report severe symptoms. It is unclear why patients' experience of AF-related symptoms varies so much. We have previously shown that patients with symptomatic AF exhibit lower pain tolerance than patients with asymptomatic AF, as well as impaired pain inhibitory control and facilitated summation of pain, indicating that pain sensitisation may be of importance in symptomatic AF. In patients with chronic pain conditions, several biomarkers and epigenetic markers associated with generation and /or maintenance of chronic pain have been identified. Previous research of biomarkers and epigenetic markers associated with pain is sparse in patients with AF.

The objective is to study levels of biomarkers and epigenetic markers in blood in patients with symptomatic paroxysmal AF (n=100), in relation to severity of AF symptoms, and compared to age- and sex-matched controls without AF (n=100). Blood will be obtained before and after AF ablation and levels of biomarkers, epigenetic markers and cardiac and inflammatory markers, analysed. Patients will complete an AF-specific symptom and a generic health-related quality of life questionnaire.

In the future, biomarkers and epigenetic markers associated with pain may be used as a tool for evaluation of patients with AF and have an impact on individualized management. Another possibility is a rationale for future studies of novel analgesics that neutralize biomarkers or antagonizes its receptors.

Inclusion Criteria:

• On waiting list for AF ablation (only symptomatic subjects are offered ablation)
• Paroxysmal AF and persistent AF (AF that is continuously sustained beyond 7 days, including episodes terminated by cardioversion after ≥7 days)
• Written informed consent

Exclusion Criteria:

• Previous pulmonary vein isolation
• Cognitive or psychiatric condition
• Diabetes mellitus
• Ischemic heart disease
• Heart failure
• Asthma
• Pregnancy
• Previous/current drug or alcohol abuse
• Previous neurological or concomitant musculoskeletal disorders
• Continuous analgesic medication

100 subjects who are planned for an AF ablation at Oerebro University Hospital, will be offered the chance to participate in the study. The subjects choice of whether they participate or not will not affect their planned ablation. The waiting list for AF ablation consists of subjects suffering from symptoms due to AF where ablation has been shown to reduce symptoms and improve quality of life.

100 controls without AF will be recruited through poster advertisements primarily at Oerebro University Hospital, Sweden. If needed, advertisements will be expanded to members of the general public who meet the inclusion criteria in the city of Oerebro, Sweden.

The study protocol and statistical analysis plan was shared with Dennis Boye Larsen and Lars Arendt Nielsen in Aalborg, Denmark over e-mail in August 2021. The clinical study report and encoded data regarding patient characteristics and results from questionnaires and blood tests will be shared with Dennis Boye Larsen and Lars Arendt Nielsen in Aalborg, Denmark, for statistical analysis. Data will be made available by an encrypted usb flash drive sent by post. There is no other plan to make individual participant data available to other researchers.

The encoded individual participant data will be available for Dennis Boye Larsen and Lars Arendt Nielsen from 1st January 2022 to the end of September 2023.

Coded data will be available upon reasonable request.