Lifestyle Modification for the Treatment of Symptomatic Atrial Fibrillation (LIFE-AF)
Lifestyle Modification for the Treatment of Symptomatic Atrial Fibrillation (LIFE-AF)
The purpose of this study is to evaluate the effectiveness of a lifestyle modification
 intervention focused on healthy eating, regular exercise and behavioural therapy to decrease
 the length and number of atrial fibrillation episodes as well as gain an understanding of the
 impact of these changes on the gut microbiome.
Proposed research:

 This pilot study will evaluate the potential efficacy and feasibility of risk factor
 modification in patients with a known history of symptomatic paroxysmal and persistent AFIB
 (in sinus rhythm) by implementing current evidence-based lifestyle recommendations as well as
 gain an understanding of the impact of these changes in the gut microbiome.

 Objectives:

 This study aims to determine if a multicomponent risk factor modification intervention
 (dietary intervention, exercise regimen and behavioural therapy) implemented using a basic
 healthcare team reduces the burden of AFIB at 12 months by decreasing the length and number
 of AFIB episodes. This study aims to assess the impact of these interventions on AFIB-related
 symptoms, quality of life and rhythm status (documented on an implantable loop recorder
 [ILR]).This study aims to examine the gut microbiota and identify potential organisms which
 may be present in higher concentrations in patients with an elevated BMI and AFIB and how
 these organism levels may alter with dietary changes.

 Study Design:

 Baseline Screening & Follow-Up Assessments and Procedures:

 As part of our current clinical practice, all participants will undergo a clinical assessment
 which includes a 12-lead ECG and BP (this will be repeated at all follow-up visits: 1, 3, 6,
 and 12 months). Demographic data and body composition measurements (i.e. waist circumference)
 will also be obtained from participants' medical charts or from each participant directly.
 Screening for Diabetes mellitus, hyperlipidemia, obstructive sleep apnea and hypertension
 will also be completed at the first baseline visit.

 If not checked within the prior 6 months, all participants will have a baseline blood sample
 drawn at the first baseline visit to test for baseline sodium (Na), potassium (K), urea,
 creatinine, free thyroxine (T4) and thyroid stimulating hormone (TSH) (this will be repeated
 at 12 months). HbA1C (prediabetes/Diabetes mellitus testing) and a fasting lipid profile
 (hyperlipidemia testing) will also be measured at baseline and repeated at 12 months if
 applicable (i.e. HbA1C in those with prediabetes or Diabetes mellitus and a fasting lipid
 profile in those with hyperlipidemia).

 If not performed within the past 12 months, all participants will undergo a baseline
 transthoracic echocardiogram (TTE). A follow-up TTE will be repeated at the 12-month visit.

 AFIB: At the first baseline visit and all follow-up visits, AFIB-related symptom burden
 (using the AFSS - Appendix I) and quality of life (using the AFEQT - Appendix II) will be
 assessed. All participants will undergo implantation of an implantable loop recorder (ILR) at
 their first baseline visit (Appendix VIII). This device will continually record the
 participants' heart rate and rhythm for a period of 12 months and will record any episodes of
 AFIB. These data will be downloaded by a technician during each follow-up visit (1, 3, 6, and
 12 months) and stored in a secure manner. Principal and Co-Investigators will be blinded to
 these data. The ILR will be removed from participants during their final follow-up visit (at
 12 months).

 Apple Watch: All participants will be supplied with an Apple Watch in order to monitor their
 levels of physical activity (i.e. step counts and physical activity duration). For this
 reason, participants are required to own/have daily access to (i.e. provided by the research
 team) an iPhone to sync with the Apple Watch. The watch will be integrated with 2 apps
 (Cardiogram and Lose It) to record and keep track of physical activity, caloric intake and
 will also monitor heart rate. Participants will be trained on the use of the watch and apps.
 Participants will also be instructed to put this watch on first thing in the morning and not
 remove it until the evening when heading to bed throughout the duration of the trial.
 Participants will be asked to send data from the apps to the research team by email on a
 weekly basis. Participants will be asked to return the Apple Watch at their final follow-up
 visit (at 12 months).

 Physical activity: Physical activity levels will be assessed using the IPAQ and MESA TWPAS
 Questionnaire at the first baseline visit. These questionnaires will also be administered at
 all follow-up visits (1, 3, 6, and 12 months). Participants will be asked to share data from
 the Cardiogram app with the research team on a weekly basis.

 Diet: The diets of all participants will be evaluated at the first baseline visit and
 follow-ups (1, 3, 6, and 12 months) using the Mediterranean Diet Score Tool. Participants
 will be asked to enter all food consumed into the Lose It app each day and send this
 information to the research team on a weekly basis. Only participants in the intervention
 group will be provided with the Mediterranean Diet Handout at baseline.

 Gut microbiota: Participants will be provided with and trained on the use of "Poop" Kits.
 Stool samples will be collected (2nd baseline visit and at 1, 3, 6, and 12 months) and
 immediately stored at -80°C in Zymo collection devices. This deactivates active pathogens and
 preserves DNA for future extraction. Analyses will occur in the Centre for the Analysis of
 Genome Evolution and Function (CAGEF) at the University of Toronto, directed by Professor
 David Guttman. Microbial DNA will then be extracted from the frozen fecal samples and the 16S
 rRNA gene will be amplified. Analyses will be performed to determine levels of specific
 metabolites that have been strongly correlated to obesity and metabolic syndrome, namely
 monosaccharides and short-chain fatty acids (SCFAs).

 Randomization: A randomization schedule will be prepared by the data coordinating centre at
 Queens University, Kingston, Ontario using a computerized random number-generator. Random
 allocation will be determined by a participant randomization software application (Dacima
 Software Inc., IWRS: Interactive Web Response System). Participants will be randomized on a
 1:1 fashion between active intervention and control.

 Experimental arm: Multicomponent Risk Factor Modification Baseline - 12 months: Active
 Lifestyle Intervention Participants in this intervention group will undergo the baseline and
 follow-up assessments described earlier. The specific components of the experimental arm will
 be tailored to the needs of the participants at their baseline visit for the study.
 Throughout the trial, participants in this group will be called weekly by a member of the
 research team to review and discuss each component of the lifestyle intervention (diet,
 exercise, and behavioural therapy). Details of each component are explained below.

 Diet will be assessed (at baseline and all follow-up visits) using the Mediterranean Diet
 Score Tool (a 14-item questionnaire of adherence to the specified diet).Nutrition
 prescription will be based on a Mediterranean-style diet and individualized based on the
 participant's current weight and diet practices to optimize adherence. The diet will be
 comprised of recommended daily intakes of 50% carbohydrates, 35% unsaturated fats, and 15%
 protein. At baseline, basic information will be provided in written format using the
 Mediterranean Diet Handout. Data from the individuals' Apple Watches will be monitored and
 analyzed throughout the trial in order to assess compliance with these recommendations. Each
 participant will receive feedback and advice from the research assistant during weekly
 telephone sessions to motivate participants to make healthy changes to their diet in line
 with the Mediterranean Diet recommendations. Personal individual recommendations for changes
 to be introduced in the participant's diet in order to achieve a personalized goal. Research
 personnel will highlight the advantages of following this diet as opposed to the risks of not
 adhering to it. This approach has been successful in previous studies where behavioural
 intervention was used to help participants quit smoking.

 Physical activity levels will be assessed (at baseline and all follow-up visits) using the
 IPAQ and MESA TWPAS. Exercise prescription was selected by investigators based on a recently
 published Harvard Medical School Health Report 'Starting to Exercise'. This report recommends
 individuals to perform 150 minutes of moderate aerobic exercise per week (equal to >30
 minutes/day, most days of the week). Data from the individuals' Apple Watches will be
 monitored and analyzed throughout the trial in order to assess compliance with these
 recommendations. Each participant will receive feedback and advice from the research
 assistant during weekly telephone sessions to motivate participants to gradually achieve
 higher levels of physical activity. Participants will be invited to attend an optional
 exercise class in which they walk along an indoor walking track for 60 minutes biweekly at
 Providence Care Hospital, supervised by a research assistant and monitored by a medically
 qualified Co-Investigator.

 Comprehensive lifestyle intervention will include a structured behavioural change program
 that includes regular self-monitoring of food intake, by entering all food consumed into the
 Lose It app, which automatically calculates caloric intake, and physical activity. The
 qualified research assistant will facilitate participant engagement sessions by telephone on
 a weekly basis. During each session, the research assistant will assess the participant's
 current level of adherence to the diet and exercise recommendations and will motivate them to
 gradually achieve higher levels of exercise following the Harvard Medical School Health
 Report and to make healthy adjustments to their diet following the Mediterranean Diet
 Handout.

 Control arm: Baseline - 12 months: Standard Clinical Practice In addition to receiving
 standard of care AFIB treatment, participants in the control arm of this trial will undergo
 all of the same baseline screening and follow-up assessments and procedures as the
 intervention arm but will receive no lifestyle intervention (no diet, exercise regimen, or
 behavioural therapy).
Inclusion Criteria:

 -  paroxysmal or persistent AFIB (in sinus rhythm at the time of randomization)

 -  BMI > 30 kg/m^2 or a waist circumference greater than 100 cm (male) or 90 cm (female)

 -  have daily access to an iPhone

 -  have at least one of the following risk factors:hypertension, diabetes or
 pre-diabetes, hyperlipidemia, smoker, obstructive sleep apnea

 Exclusion Criteria:

 -  Permanent AFIB (AFIB lasting > 1 year)

 -  Prior or actively on waiting list for catheter ablation for AFIB

 -  History of unstable angina not corrected with revascularization

 -  Left ventricular ejection fraction <30%

 -  Left atrial size >5.5 cm

 -  New York Heart Association (NYHA) classification IV heart failure

 -  Moderate or severe cardiac valvular lesion (stenosis or regurgitation) on
 echocardiography or valvular lesion requiring intervention.

 -  Participation in a cardiac rehabilitation program within the last year

 -  Serious underlying psychiatric disorder: e.g. eating disorder, severe psychotic
 disorder with recent (3 month) hospitalization or psychiatric illness requiring
 supervised care precluding full independent function.

 -  Participants who are unable or unwilling to provide fully informed consent.

 -  Currently performing exercise training 150 minutes/week of moderate to vigorous
 physical activity

 -  Gastrointestinal malabsorption disorder: A previously diagnosed gastrointestinal
 malabsorption disorder interfering with macro or micronutrient absorption.

 -  If receiving warfarin and unstable international normalized ratio (INR) defined as
 persistently outside of the therapeutic range (2.0-3.0) for greater than 14
 consecutive days.

 -  Other non-cardiovascular medical conditions making 1-year survival unlikely.