Super-Rehab: a Novel Approach to Reverse Atrial Fibrillation

Study Overview
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Brief Summary
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The Super Rehab: a novel approach to reverse atrial fibrillation? study proposes to test the use of a novel lifestyle intervention (Super Rehab), in addition to standard care, for patients with symptomatic atrial fibrillation (AF) requiring rhythm control strategy who are overweight. As the main driver behind the selection of a rhythm-control strategy for patients with AF, the primary outcome will be an improvement in AF-related symptoms with Super Rehab versus Usual Care only. Key secondary outcomes will include the burden of AF, change in stroke risk, biochemical and cardiac functional and structural changes, and markers of quality-of-life and health economic costs.

Detailed Description
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In this randomised controlled trial (RCT) the investigators will study the efficacy of a novel lifestyle intervention (Super Rehab), in addition to usual care, for patients with symptomatic atrial fibrillation (AF) where are a rhythm-control strategy is being employed who are overweight. Increasing evidence has shown that AF can respond to robust lifestyle change and aggressive risk factor modification, and in some case can in fact regress. In the majority of cases, the decision to target a rhythm-control strategy for AF is based on the symptom-burden reported by the patient. This in light of the low volume of evidence suggesting any benefits of rhythm-control strategies over rate-control strategies based on prognostic clinical outcomes. The modifiable cardiovascular (CV) risk factors that increase both CV risk and the frequency of its various forms of disease also impact the development and progression of AF. In addition, patients with multiple CV risk factors are at enhanced risk of both poorer long-term outcomes and earlier failures of traditional rhythm-control strategies. This RCT study will involve patients who have described symptomatic AF such that their treating team have elected a rhythm-control strategy (i.e. a combination of anti-arrhythmic therapy ± a referral for a direct current (DC) cardioversion and/or an ablation) who are also overweight (body mass index [BMI] ≥27kg/m2). The BMI criterion acts as a marker of CV risk that may respond to a lifestyle intervention, which has proved sensitive in other studies. Participants will be randomised to either Super Rehab and Usual Care or to continue Usual Care only. Super Rehab includes a combination of 1:1 supervised high-intensity exercise, dietary advice sessions and 3-monthly clinical reviews to optimise CV risk factor management. The whole programme lasts 12 months. Participants in both arms will undergo imaging, fitness, clinical tests (including blood tests), and complete questionnaires on four occasions during the study. The primary outcome of the study will assess the difference in AF symptom burden between the two groups. In addition, the study will assess important secondary outcomes that include change in AF burden (i.e. the amount of time spent in AF), stroke risk, quality-of-life and well-being, biochemical, anthropometric, blood pressure and cardiac functional and structural changes, and a cost-effectiveness analysis.

Official Title
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Super Rehab: A Novel Approach to Reverse Atrial Fibrillation (a Randomised Controlled Trial)

Conditions
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Atrial Fibrillation, Overweight and Obesity

Intervention / Treatment
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* Behavioral: Super Rehab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged >18 Symptomatic AF (paroxysmal or persistent <12-months) with a rhythm control management strategy selected including consideration of referral for a cardioversion or ablation forming part of their planned pathway BMI ≥27m/kg2 Exclusion Criteria: Prognostic coronary artery disease, defined as left main stem >50% stenosis or ≥ moderate disease in ≥3 major epicardial vessels Unstable angina New York Heart Association class III/IV heart failure or severe left ventricular impairment Significant cardiomyopathy (as assessed by Cardiologist, e.g. hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy) Severe heart valve disease Severe hypertension (BP >180/120mmHg) despite optimising anti-hypertensive therapy Uncontrolled arrhythmia or higher degree heart block History of aortic dissection Recent acute pulmonary embolus, deep vein thrombosis, stroke or transient ischaemic attack Severe autonomic or peripheral neuropathy Acute systemic illness of fever Significant acute or chronic renal failure Pulmonary fibrosis or interstitial lung disease Physically unable to participate in high-intensity exercise Pregnancy Prior atrial fibrillation ablation A clinically significant ECG abnormality at the screening visit, which in the opinion of the investigators exposes the subject to risk by enrolling in the trial Participation in another intervention-based research study Inability to fully understand the instructions provided during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients randomized to Usual Care or Super Rehab plus Usual Care
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual Care<br>Patients will continue Usual Care, which will include having medication optimised for adequate heart-rate control, anti-arrhythmic therapy, and anti-coagulation (for stroke-risk) instituted by their treating Cardiologist if indicated by their CHA₂DS₂-VASc Score. Patients who remain significantly symptomatic despite attempts to optimise medical therapy may be referred for further rhythm management strategies, including cardioversion(s) and/or ablation(s) - as per current standard clinical practice. The Cardiologist will also provide routine, verbal one-off lifestyle advice in line with guidance. | |
| Experimental: Super Rehab plus Usual Care<br>12-month Super Rehab programme involving supervised dietary review sessions, 1-to-1 high-intensity exercise sessions and 3-monthly clinical review of AF risk factors, alongside Usual Care (defined above) | Behavioral: Super Rehab<br>* A 12-month healthcare-delivered lifestyle intervention involving exercise, nutritional support and optimisation of AF-related clinical risk factors.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in symptoms, as defined by the University of Toronto Atrial Fibrillation Severity Scale | As the primary outcome, an atrial fibrillation specific measure of symptoms and quality-of-life will be assessed with the University of Toronto Atrial Fibrillation Severity Scale questionnaire. Scores range from 0 to 35, with higher scores indicating greater AF symptom severity. | Month 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from AF at 12-months | Assessed by implantable cardiac monitor, with AF taken as any atrial arrhythmia ≥30s | Month 12 | 
| Change in burden of AF | Defined as the duration of time spent in AF, assessed via implantable cardiac monitor | Month 15 | 
| Time to arrhythmia recurrence | Defined as the time from normal rhythm to the earliest date with documented AF, and only confirmed events will be included in the analyses | Month 15 | 
| Change in stroke risk - defined by Atriomic Stroke Algorithm | Assessed by peri-left atrial signal on cardiac CT, the Atriomic Stroke Algorithm | Month 12 | 
| Change in stroke risk - defined by CHA₂DS₂-VASc | Assessed using the well-established stroke risk prediction score (CHA₂DS₂-VASc) at baseline and follow-up, where higher scores indicated heightened risk of suffering a stroke | Month 12 | 
| Change in atrial fibrillation symptoms, as defined by the European Heart Rhythm Association (EHRA) AF-score | Patients will be asked to provide their European Heart Rhythm Association (EHRA) AF-score, a simple simple score from 1 (no symptoms) to 4 (disabling symptoms) will be recorded at baseline, 6, 12 and 15 month time-points. | Month 15 | 
| Change in patient reported health-related quality-of-life, measured with the EuroQol Group (EuroQol) EQ-5D-5L questionnaire | Patient reported health-related quality-of-life will be recorded using the EuroQol EQ-5D-5L questionnaire. This will be recorded at baseline, 6, 12 and 15 month time-points. | Month 15 | 
| Change atrial fibrillation specific quality of life with the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) Questionnaire | Atrial Fibrillation Effect on QualiTy-of-life [AFEQT]. The questionnaire involves 20 questions - The Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) Questionnaire involves responses to a 20-item questionnaire that are scored on a 1 to 7 Likert scale (ranging from 1: Not at all to 7: Extremely). The four subscales of AFEQT are: Symptoms, Daily activities, Treatment concern and Treatment satisfaction. Overall and subscale scores range from 0 for worst to 100 for best quality of life. This will be recorded at baseline, 6, 12 and 15 month time-points. | Month 15 | 
| Change in self-perceived mental health, assessed with the Hospital Anxiety and Depression Scale (HADS) | Hospital Anxiety and Depression Scale (HADS). Scores range from 0 to 21 with higher scores reflecting a higher degree of anxiety and/or depression. | Month 15 | 
| Change in measure of capability | The ICEpop CAPability measure for Adults (ICECAP-A) will assess holistic capability changes over time as part of a health economic assessment. Scores range from 5 to 20, with higher scores reflecting higher levels of capability. | Month 15 | 
| Change in resource-use, measured with a study specific resource-use questionnaire | A study-specific resource-use questionnaire will record health economic parameters including medication burden, primary and secondary care interactions, impact of AF on work status, and smoking status. | Month 15 | 
| Change in serum lipid levels | Blood samples will be taken for the lipid profile. | Month 15 | 
| Change in glucose control, measured with the glycated haemoglobin test (HbA1c) | Blood samples will be taken for HbA1c to track changes in glucose control over time. | Month 15 | 
| Inflammatory markers (e.g. high-sensitivity C-reactive protein) | Blood samples will be taken for inflammatory markers (e.g. high-sensitivity C-reactive protein). | Month 15 | 
| Anthropometrics - abdominal waist circumference | Change in abdominal waist circumference (centimetres) will be reported. | Month 15 | 
| Anthropometrics - body mass index | Change in body mass index (BMI) will be reported using aggregated height (metres) and weight (kilograms) to arrive at one reported value (kg/m^2). | Month 15 | 
| Body composition | Changes in body fat composition will be assessed with dual-energy X-ray absorptiometry (DEXA). | Month 15 | 
| Cardiorespiratory fitness | Serial cardiopulmonary exercise tests will provide a measurement of maximum rate of oxygen consumption attainable during physical exertion (VO2 peak), reported in mL/kg/min. | Month 15 | 
| Blood pressure control | 7-day home blood pressure diary, including both systolic and diastolic recorded in mmHg. | Month 15 | 
| Cardiac structural assessment with echocardiography | An assessment of cardiac chamber size will be performed using echocardiography. | Month 15 | 
| Cardiac systolic function assessment with echocardiography measure of left ventricular ejection fraction | An assessment of cardiac systolic function, defined by left ventricular ejection fraction, will be performed using echocardiography. | Month 15 | 
| Cardiac systolic function assessment with echocardiography of left ventricular strain | An assessment of cardiac systolic function, defined by left ventricular strain, will be performed using echocardiography. | Month 15 | 
| Cardiac diastolic function assessment with echocardiography measurement of left ventricular filling pressure | An assessment of cardiac diastolic function, with echocardiography measure of left ventricular filling pressure. | Month 15 | 
| Echocardiography left atrial strain assessment | An assessment of left atrial strain, a marker of atrial function, will be performed using echocardiography. | Month 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lifestyle risk reduction, Exercise, Behavior modifications, Nutrition therapy, Diet, Cardiovascular disease