Atrial fibrillation (AF) is the most common arrhythmia, diagnosed in approximately 50 million people worldwide. Its prevalence is expected to increase, eventually affecting every third person, which will result in significant healthcare costs. AF symptoms include palpitations, shortness of breath, and fatigue. The condition may lead to discomfort from symptoms and medical treatment, reduced quality of life, and an increased risk of heart failure, stroke, and death. High alcohol intake can cause AF, trigger new episodes and worsen the condition.

The aim of this project is to determine the effect of six months of alcohol abstinence after atrial fibrillation ablation, as modifiable risk factors have gained more attention in the prevention and treatment of AF. Secondly, this study will provide new insights into utilizing a technology platform that enables wearable devices to collect health data remotely. This approach makes ready-to-wear devices a simple and effective solution for monitoring patients' health from home.

The study is designed as an open-label, pragmatic, prospective, 1:1 Randomized Controlled Trial (RCT) that will be preceded by a feasibility study (n=40) that will test the feasibility of the proposed inter-vention for the RCT study. The intervention consists of six months of alcohol abstinence after the ablation procedure. To ensure the best possible chance to succeed with complete alcohol absti-nence, the patients will be offered guidance and support from nurses at the hospital based on the techniques of motivational interviewing.

After evaluating the outcomes of the feasibility study, appropriate adjustments will be made. All participants from the feasibility study will be included in the RCT study.

The study will include a total of 414 participants. The feasibility will be evaluated in five main objec-tives according to the Medical Research Council guidance for designing and evaluating complex in-terventions: Recruitment, data collection, acceptability, resources spent and participant responses.

The primary outcome of the RCT study is AF recurrence after 6 months measured with Withings Scanwatch 2. Secondary outcomes are Number of days with AF, change in AUDIT score, change in symptom burden (AFSS score), change in health-related quality of life (EQ-5D-5L), change in alcohol consumption (self-reported and Peth analysis), change in antiarrhythmic medicine and sick leave days.

Part two of the study will investigate the long-term effect of alcohol abstinence after atrial fibrilla-tion ablation. Primary outcome is time to AF and secondary outcome is re-ablations, hospital admis-sions and antiarrhythmic therapy. Lastly, a cost-utility analysis will be performed.

Background

Atrial fibrillation Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and the lifetime risk of de-veloping AF is approximately one out of three. It has a prevalence of approximately 50 million peo-ple worldwide which is expected to increase which entails significant health care costs. AF symp-toms include palpitations, shortness of breath, and fatigue. The condition may lead to discomfort from symptoms and medical treatment, reduced quality of life, and an increased risk of heart fail-ure, stroke, and death. The medical treatment of AF consists of rhythm and rate control together with anticoagulants. Ablation treatment is an effective way to prevent AF episodes, reduce symp-toms and improve quality of life. Sinus rhythm is restored by destroying the electrical impulses that cause the arrhythmia. The cornerstone of the treatment is isolation of the pulmonary veins, where the AF typically originates in otherwise healthy individuals. The electrical impulses can be treated via invasive catheters that reach the heart through the veins in the groin. The long-term success rate varies from 50-80 %. Typically, AF progresses over time from paroxysmal to persistent to per-manent due to structural remodeling of the atrium, described in the literature as 'AF begets AF'. Risk factors for the development of AF include age, male gender, ischemic heart disease, hyperten-sion, and heart failure. In Denmark, the number of ablation treatments is increasing primarily be-cause of an increasing number of AF patients. Modifiable risk factors such as obesity, physical inac-tivity, smoking, and alcohol consumption, have gained more attention in preventing AF and improv-ing the outcome of the treatment of AF. The phenomenon 'holiday heart syndrome' was first de-scribed by Ettinger et al in 1978. It is an alcohol-induced arrhythmia in a person without other clinical evidence of heart disease. Several studies have since then shown a dose-response dependent relationship between alcohol consumption and the development of AF, and even alcohol in small doses is reported to be a common trigger for AF episodes. A recent study involving 140 patients showed that it is possible to reduce the burden of AF by abstaining from alcohol. Alcohol's effect on the recurrence of AF is not yet fully understood but is probably related to an increased number of low-voltage zones in the heart. Evidence about improving the outcome of AF ablation by reduc-ing alcohol intake is scarce and more robust studies are needed to investigate how modifiable risk factors, like alcohol, affect the success rate of ablation treatment. Therefore, this study aims to investigate how alcohol abstinence affects the outcome of atrial fibrillation ablation treatment.

Methods

Design The study is designed as an open-label, pragmatic, prospective, 1:1 Randomized Controlled Trial (RCT) that will be preceded by a feasibility study that will test the feasibility of the proposed intervention for the RCT study. The intervention will be led by health professionals and will focus on alcohol abstinence.

After evaluating the outcomes of the feasibility study any appropriate adjustments will be made.

All participants from the feasibility study will be included in the RCT study that will test if six months of alcohol abstinence after AF ablation will improve the outcome of the AF ablation. Lastly, there will be performed a cost-utility analysis of the intervention.

Patients will be recruited from the only site in Denmark's Capital Region that perform AF ablation treatments, RH. Patients will be recruited at a telephone consultation before their AF ablation treatment.

All patients will answer the three first questions of the Alcohol Use Disorder Identification Test (AUDIT) questionnaire, also called AUDIT-C (AUDIT-Concise) before the ablation treatment as part of a standard questionnaire. The AUDIT is a 10-item questionnaire developed by WHO and is a vali-dated screening tool to assist in early detection of people who drink in a way that is potentially or currently harmful to health. A score of 0-7 indicating low risk drinking, 8-15: Indicating hazardous drinking, 16-19: Indicating harmful drinking, 20+: indicating high risk drinking and dependency. The AUDIT score will serve as an inclusion criteria when the AUDIT-C score ≥3. If the AUDIT-C score is missing, we will include patients who drinks ≥3 drinks per week.

Baseline (time 0) At the day of the procedure baseline demographics will be collected, symptom burden is measured with Atrial Fibrillation Severity Scale (AFSS), Health Related Quality of Life is measured with EQ-5D-5L, and there will be collected data on self-reported physical activity level and self-reported stress level. Patients will complete the full AUDIT questionnaire. Patients are instructed in the use of the Withings Scanwatch2 that is handed to all patients in the study. They are instructed in how to send a daily ECG recording and when experiencing symptoms. They are asked to register days of sick leave. Patients from both groups will be asked to complete a log of their alcohol intake using the Timeline follow-back method, a tool designed to help recall alcohol consumption during the two weeks prior to inclusion and they will be asked to complete alcohol logs regarding the two weeks before outcome assessment at 6 months. Further, the intervention group will also complete a log during the intervention phone calls. Finally, a blood test Phosfatidyletanol (PEth, an alcohol marker that can measure alcohol intake up three weeks prior the bloodtest) will be measured at baseline and at 6 months.

Randomisation Randomisation and allocation will be conducted 1:1 using randomization software and stratified on gender and AUDIT score. Randomisation takes place at the day of the ablation procedure (time 0).

Blinding Because of the nature of the study, it is not possible to blind the participants, or the health profes-sionals involved. All analysis of the ECG's and the data analysis will be performed blinded by health professionals and statisticians respectively.

Intervention and Control

The intervention consists of six months of alcohol abstinence after the AF or AFL ablation. To en-sure the best possible chance to succeed with complete alcohol abstinence, the patients will be offered guidance and support according to the AUDIT score as follows:

1. AUDIT <20 receives support from hospital nurses
2. AUDIT ≥20 receives support from hospital nurses and will be encouraged also to seek help elsewhere such as 'Alkolinjen' or 'Overkanten'.

The support consists of approximately 2-6 face-to-face/online/telephone consultations based on individual needs and using the techniques of motivational interviewing. Health professionals involved in the project are formally trained in the technique.

The control group receives usual care which means no focused nurse intervention and no re-strictions regarding alcohol intake but will be advised according to existing guidelines.

Statistical considerations There are no rules about sample size in feasibility studies but different guidelines. We will use the feasibility study to optimize the workflow related to the inclusion process.

For the RCT study, we estimate that a clinically relevant difference on the primary outcome would be a change of 12 % and therefore expect that 83 % in the intervention group will be free of AF and 71 % in the control group. Based on a fisher's exact test the sample size assumes a power of 80 %, an α of 5% the final number of participants reaches 414 with 207 in each group.

Each year, RH perform around 1000 first time AF ablations and the productivity is increasing. With the estimate that 25% of all patients who fulfill inclusion criteria's wish to participate in the study we believe to succeed with inclusion within a timeframe of 2-3 years.

Descriptive statistics will be used to present baseline characteristics and continuous variables will be presented as mean and standard deviations (SD). Categorical variables will be summarized as fre-quencies and percentages. Analyses of dichotomous outcomes will be done using logistic regres-sion. Linear regression is used for continuous outcomes. The intention to treat principle will be ap-plied, accounting for missing values by multiple imputations by chained equations. In addition, we will perform a per-protocol analysis. For part II of the study, time to AF, we will use time-to-event methods such as Cox proportional hazard model.

Inclusion Criteria:

• All patients >18 years old
• Referred to a first-time AF or AFL ablation
• Scores ≥3 on AUDIT/ ≥3 drinks per week
• Can use the ScanWatch2 as described

Exclusion Criteria:

• Patients who do not have a Danish social security number
• Patients who cannot read, and speak Danish fluently
• Unable to give informed consent.