Alcohol as a Modifiable Risk Factor for Atrial Fibrillation (AFFAIR)

AFFAIR - Alcohol as a Modifiable Risk Factor for Atrial Fibrillation

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation (AF)
• Intervention / Treatment: Behavioral: alcohol abstinence

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 414
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Camilla N Bring, PhD student; Phone Number: +4535458869; Email: camilla.nygaard.bring.01@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Six months of alcohol abstinence after atrial fibrillation ablation treatment.	Behavioral: alcohol abstinence; To ensure the best possible chance to succeed with complete alcohol abstinence, the patients will be offered guidance and support through nurse consultations, based on motivational interviewing. Each patient will be offered approximately 2-6 face-to-face/online/telephone consultations. Patients that score ≥20 on the Alcohol Use Disorder Identification Test (AUDIT) will be encouraged also to seek help from a alcohol addiction consultant.
No Intervention: Control group; The control group receives usual care (SOC) after atrial fibrillation ablation treatment. That means no focused nurse intervention and no restrictions regarding alcohol intake but will be advised according to existing guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atrial fibrillation recurrence	AF recurrence in the two groups, defined as incidences that last >30 sec. from 3-6 months. There will be a 3-month blanking period as atrial fibrillation can occur in the first three months after the ablation procedure, even though it has been a successful treatment.	6 months
Time to atrial fibrillation (part two)	We follow all patients until 1 year after including the last patient	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days with AF	defined as incidences that last >30 sec.	3 to 6 months
Symptom burden assessed with Atrial Fibrillation Severity Scale (AFSS) questionaire	The AFSS questionnaire is a validated patient-reported outcome measure used to assess the severity and impact of AF. The AFSS evaluates four domaines: burden, helath care utilization, symptoms and global well-being. Scores range from 3-30, with higher scores indicating greater AF severity and symptom burden.	6 months
Health Related Quality of Life meassured with the EQ-5D-5L self-reported questionnaire	The EQ-5D-5L is a validated patient-reported questionnaire assessing health-related quality of life across five domains: mobility, self-care, ususal activities , pain/discomfort, and anxiety/depression. Responses are converted into a single index score reflecting overall health status, with higher scores indicating better health-related quality of life. The questionnaire also includes a visual analogue scale ranging from 0-100, where higher scores indicate better perceived health.	6 months
Alcohol consumption	Alcohol consumption is measured as grams per week according to their alcohol log. It is measured at baseline and at 6 months, using the Timeline follow-back method recalling alcohol consumption 2 weeks prior inclusion and 2 weeks prior outcome assesment. Intervention group will also asked about alcohol consumption at intervention consultations.	6 months
Fosfatidyletanol (PEth)	A biomarker that can detect alcoholconsumption up to 3 weeks before the blood test	3 weeks
Antiarrhythmic therapy	Antiarrhythmic therapy is compared between groups	6 months
Sick leave days	Participants are being asked to register number of sick leave days	6 months
Mortality	mortality in both groups	6 months
Re-ablation procedure (part two)	Data about re-ablation will be retrieved from the Danish Atrial Fibrillation database	1 year
Hospital admissions (part two)	Hospital admissions including DC-Cardioversions	1 year
Antiarrhythmic therapy (part two)	Antiarrhythmic therapy in the two groups	1 year
Mortality (part two)	Mortality in both groups	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment (feasibility)	The recruitment rate will be evaluated, and the feasibility will be measured as a percent of the total patient population estimated to be in the target group. The criteria are supported if 80% of the total patient population is deemed acceptable for inclusion.	6 months
Data collection - detection of at-risk drinking (feasibility)	The data collection method will be evaluated to see: 1. If it is suitable and feasible to detect patients with at-risk drinking. The criterion is supported if 75 % of the total patient population answer the AUDIT questionnaire.	6 months
Data collection - ECG's collected through smartwatch (feasibility)	The data collection method will be evaluated to see: If it is achievable to receive ECG from a smartwatch once a day, and when the patients ex-perience symptoms (at the beginning and end of symptoms). The criterion is supported if we receive 80 % of the ECG's during the feasibility period.	6 months
Data collection - monitoring activity level with smartwatch (feasibility)	The criterion will be evaluated to see if it is possible to monitor patients' activity level with the use of a smartwatch. This will be evaluated based on patients' feedback regarding using the smartwatch continuously during the feasibility period.	6 months
Data collection - questionnaires (feasibility)	Feedback from patients will be used to evaluate if the total amount of questionnaires is manageable and if they think there could be any barriers to the data collection process.	6 months
Acceptability (feasibility)	The acceptability of the intervention will be deemed feasible if 25 % of the patients who scores >3 on the AUDIT questionnaire accept participation and 80 % will initiate the intervention.	6 months
Resources (feasibility)	Time used for administration of intervention will be registered.	6 months
Participant responses (feasibility)	Feedback from patients and health care professionals in the project will be used to assess the likelihood of success and address challenges with the intervention. Patients will be asked to answer questions about whether any other health professional has discussed alcohol habits and whether they find this approach suitably and comfortable.	6 months

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Estimated): April 20, 2026
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: atrial fibrillation, atrial fibrillation ablation, risk factors, modifiable risk factor modification, alcohol, alcohol abstinence,
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Drinking Behavior; Pathological Conditions, Signs and Symptoms; Behavior; Atrial Fibrillation; Alcohol Abstinence; Organic Chemicals; Alcohols; Ethanol
• Other Study ID Numbers: H-25013209

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No