Atrial Fibrillation
Conditions
Brief summary
A multi-center, randomized trial to examine the effect of aggressive risk factor control and arrhythmia trigger-based intervention on recurrence of atrial fibrillation.
Detailed description
Atrial fibrillation (AF) is a major health problem, with a prevalence of 0.4-1% of the population. It results in high healthcare costs and significant morbidity, especially for patients with severe symptoms. Exercise and risk factor modification to prevent and modify AF has garnered a significant amount of support in cohort studies that have proven benefit. It is well known that age, body mass index, valvular heart disease, heart failure, hypertension and sleep apnea are risk factors for AF, most of which are modifiable if targeted appropriately. In addition, catheter ablation techniques have evolved and improved to reduce AF recurrence in those who are most symptomatic, and either have heart failure, or are at risk for its development. Despite these advances, the recurrence of AF remains high. We propose to determine whether early treatment of the arrhythmogenic substrate, with or without aggressive risk factor modification, is most important in prevention of recurrent AF. It is hypothesized that patients with underlying risk factors that promote AF will benefit most from a combined strategy of aggressive risk factor modification in combination with catheter ablation. The study design will be a two-arm, parallel group, randomized clinical trial comparing catheter ablation versus catheter ablation plus aggressive risk factor therapy, followed by maintenance with blinded endpoint evaluation. Patients with symptomatic AF and two of the following will be included: BP ≥ 140/90 or history of hypertension, BMI≥27, diabetes, prior stroke/TIA, history of heart failure (prior heart failure admission due to AF or LVEF\<40%), age≥65. Patients will be excluded if they are exercising \>150 minutes/week by self-report. Patients will be randomly allocated to one of the following groups: 1) AF ablation within 3 months, 2) AF ablation at 3 months, with a 12 week home-based exercise/risk factor management program, followed by maintenance therapy. A 5-month treatment period will be observed to deliver the interventions and have a 2 month blanking period post ablation. Guideline-directed therapy for risk factors will occur in all groups, including BP, cholesterol, diabetes, alcohol reduction and sleep apnea screening. All patients will undergo implantation of an implantable cardiac monitor (ICM) at baseline. The primary outcome will be a composite of clincally significant AF (AF ≥ 24 hours), AF-related hospitalization/emergency department visits 5 months post randomization. Secondary outcomes will include: Death, Stroke or Systemic embolism, Quality of Life, Health Outcomes, recurrent AF, & AF burden. The minimum sample size required is 500. Safety outcomes include: AF catheter ablation procedural complications, Anti-arrhythmic medication related adverse events, & Death.
Interventions
1. Sleep apnea screening, therapy is recommended if apopnea-hypopnea (AHI) index is greater than 15, with a target index of less than 5. 2. Counseling regarding alcohol reduction to 2 drinks/day for men, 1 drink/day for women, no binge drinking (\>5 drinks at one setting). 3. Participation in a 12 week structured, home-based exercise program and nutritional counseling. Weight reduction will be emphasized through modification of diet and exercise. 4. Blood Pressure management to achieve a target systolic blood pressure (SBP) of \<120/80 mm/Hg 5. Smoking cessation facilitated through local resources already established at each site
OTHERStandard of Care
Recommendations based on current guidelines
Sponsors
Nova Scotia Health Authority
Canadian Institutes of Health Research (CIHR)
Abbott
Philips Healthcare
Cardiac Arrhythmia Network of Canada
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This will be a parallel group, open label randomized clinical trial, with blinded endpoint evaluation (PROBE design)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients with symptomatic (CCS-SAF ≥2) paroxysmal or persistent atrial fibrillation despite rate control, desiring catheter ablation and at least two of the following: * BMI ≥ 27, * BP ≥140/90 mmHg or history of hypertension, * Prior stroke/transient ischemic attack, * Diabetes, * Heart failure (prior heart failure admission or left ventricle ejection fraction (LVEF) \<40%), * Age ≥ 65 years * Current smoker * Excessive Alcohol use
Exclusion criteria
* Permanent AF (AF lasting \> 3 years) * Prior catheter ablation for AF * New York Heart Association (NYHA) Class IV (Severe) heart failure, * Participation in a cardiac rehabilitation program within the last year, * Currently performing exercise training \>150 minutes/week of moderate to vigorous physical activity, * Unable to exercise, * Unable to give informed consent, * Other noncardiovascular medical condition making 1 year survival unlikely, * Less than 18 years of age.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of AF related hospitalizations post ablation | up to 72 months | AF-related hospitalizations (lasting more than 24 hours) from 2-months post ablation to end of follow up. |
| Number of AF related Emergency Department (ED) visits post ablation | up to 72 months | AF-related emergency department visits from 2-months post ablation to end of follow up. |
| Number of clinically significant AF events post ablation | up to 72 months | Clinically significant AF events lasting \>24 hours (either an irregular R-R interval, or atrial cycle length \< 280 ms, as obtained from an insertable cardiac monitor) from 2-months post ablation to end of follow up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of AF-related hospitalizations | up to 72 months | AF-related hospitalizations (lasting more than 24 hours) from randomization to end of follow up. |
| Number of AF-related emergency department (ED) visits | up to 72 months | AF-related emergency department visits from randomization to end of follow up. |
| Number of Clinically significant AF events | up to 72 months | Clinically significant AF events lasting \>24 hours (either an irregular R-R interval, or atrial cycle length \< 280 ms, as obtained from an insertable cardiac monitor) from randomization to end of follow up. |
| Mean AF burden | up to 72 months | Average percentage of time in AF during follow up, as measured by insertable cardiac monitor. |
| Stroke or systemic embolism events | up to 72 months | Total number of stoke or systemic embolism events. |
| Quality of Life - CCS-SAF | Up to 24 months | Symptom burden as measured by the Canadian Cardiovascular Society (CCS) Severity of Atrial Fibrillation (SAF) scale. CCS-SAF scores range from 0 to 4, with higher values representing more severe impact of symptoms on quality of life and activities of daily living. |
| Quality of Life - AFEQT | Up to 24 months | Quality of life as measured by the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) scale. The scale consists of 21 questions with 7-point Likert scale responses. Questions 1-18 are grouped into three subscales (symptoms, daily activities and treatment concern). Questions 19-21 capture satisfaction with treatment and are not include in the HRQoL score of the questionnaire. Overall and subscale scores range from 0 to 100. Lower scores correspond to higher levels of disability (e.g., 0 corresponds to complete disability or responding "extremely" limited, difficult or bothersome to all questions answered), while a score of 100 corresponds to no disability (e.g., responding "not at all" limited, difficult or bothersome to all questions answered). For Satisfaction questions, a score of 100 corresponds to extreme satisfaction with current treatment. |
| Number of recurrent AF-ablations | up to 72 months | Number of re-ablations required. |
| Cardioversions | up to 72 months | Number of cardioversions required. |
| All-cause mortality | up to 72 months | Any deaths occurring at any time during the study. |
| AF at any time | Up to 72 months post randomization | Atrial fibrillation (confirmed by ICM, 12-lead ECG or telemetry) |
| Health Outcomes | Up to 24 months | Measured by the Euroqol-5D-5L questionnaire |
| Association between gender, AF risk factors and aggressive risk factor management | UP to 24 months | This will be determined by the use of the GENESIS Praxy Gender questionnaire |
| Major Bleeding | Up to 72 months | Any event which includes the following criteria: fall in Hgb of ≥2 g/dL, transfusion of ≥2 units PRBC or whole blood, in a critical location (e.g., intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial), causes death |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORRatika Parkash
Nova Scotia Health Authority
STUDY_DIRECTORAllan Skanes
London Health Sciences Centre
STUDY_DIRECTORChris Blanchard
Nova Scotia Health
STUDY_DIRECTORDavid Birnie
University of Ottawa Heart Institution
STUDY_DIRECTORGeorge Wells
University of Ottawa Heart Institution
STUDY_DIRECTORMichiel Rienstra
University of Groningen
STUDY_DIRECTORJeff Healey
Hamilton Health Sciences Centre
STUDY_DIRECTORJennifer Reed
University of Ottawa Heart Institution
STUDY_DIRECTORAnthony Tang
London Health Sciences Centre
STUDY_DIRECTORVidal Essebag
McGill University Hospital
STUDY_DIRECTORIsabelle vanGelder
University of Groningen
STUDY_DIRECTORJohn Sapp
Nova Scotia Health Authority
Outcome results
None listed