Genetic Risk-Based Atrial Fibrillation Screening (GeneAF Study)

Study Overview
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Brief Summary
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AF is the most common sustained arrhythmia in adults and its prevalence increases with advancing age. In this study, we aim to determine whether the published genome-wide polygenic scores for atrial fibrillation (GPSAF) can facilitate AF screening by accurately discriminating between patients with low and high risk for AF. All included patients are participating in the MHI biobank, an ongoing funded institutional DNA bank and clinical registry approved by the research ethics board where included patients consent for future genetic research. The study will compare AF detection rate using a 3 months near continuous monitoring in individuals with a high GPSAF with matched individuals from the bottom GPSAF.

Detailed Description
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In Canada, 50,000 strokes occur every year and can have devastating consequences on patients. Approximately 15% of strokes are attributable to an undiagnosed arrhythmia, atrial fibrillation (AF). Strokes due to AF are more severe and lethal but are preventable with anti-coagulation. Most patients who suffer from AF are asymptomatic and thus don't come spontaneously to medical attention. The diagnosis can be made by electrocardiographical (ECG) recording. As longer recordings spanning on weeks and months are often required, it is not possible to apply this intense screening to the entire population. The GeneAF project thus aims to use genetic information to identify and target patients who benefit the most from a more intensive screening approach. A previously published genetic polygenic risk score (GPS) for AF has been shown to be associated with prevalent AF in the UK biobank population. Participants in the top 5 percentile were three times more likely to have a history of AF (prevalent AF). The aim of this project is to determine if the use of this previously published GPS score for prevalent AF can be used to screen for silent incident AF in our population. Primary objective: To assess the association of GPSAF with silent AF and compare AF detection rates in patients with a high GPSAF to matched controls. Secondary objectives: To determine the proportion of patients with identified AF who will be prescribed anticoagulation during follow-up. Methods: The GeneAF study is a cohort study comparing AF detection rate using a 3 months near-continuous monitoring in individuals with a high GPSAF (top 5%; High Risk group) with matched individuals from the bottom 95% GPSAF (Lower Risk group). All included subjects are current participants in the MHI biobank. Only candidates who would be considered for anticoagulation in case AF is detected (actionable AF; CHADS-65 > 1. We estimate that approximately 350 patients per group will be needed.

Official Title
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Genetic Risk-Based Atrial Fibrillation Screening

Conditions
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Genetic Predisposition, Atrial Fibrillation

Intervention / Treatment
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* Diagnostic Test: Resting ECG (if first visit is done on site only)
* Diagnostic Test: 24-hour ambulatory electrocardiographic monitoring (Holter) (if first visit done on site only)
* Diagnostic Test: 3-month AF detection monitoring using the Apple Watch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having a CHADS65 score>1, which requires either: Age >= 65 and/or A prior Stroke or TIA and/or Hypertension and/or A history of heart failure and/or Diabetes Exclusion Criteria: Already on oral anticoagulation Any prior history of AF or atrial flutter (AFl) Patients currently having an implantable device (pacemaker, defibrillator or loop recorder) that allows detection of AF/AFl Refusing testing with the Apple Watch

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| High-Risk group<br>: Montreal Heart Institute biobank participants with a high specific genome-wide polygenic risk scores for atrial fibrillation G | Diagnostic Test: Resting ECG (if first visit is done on site only)<br>* The standard 12-lead electrocardiogram is a representation of the heart's electrical activity recorded from electrodes on the body surface. This test requires around 15 minutes of the participant's time.<br>Diagnostic Test: 24-hour ambulatory electrocardiographic monitoring (Holter) (if first visit done on site only)<br>* The Holter monitor is a type of portable electrocardiogram (ECG) worn continuously for 24 hours.<br>Diagnostic Test: 3-month AF detection monitoring using the Apple Watch<br>* Patients with irregular heart rates will be notified by the Apple Watch and instructed to confirm the rhythm by using the integrated ECG recording system. This simply requires touching the watch with a finger from the opposite hand and provides a 30 seconds one-lead ECG recording of diagnostic quality. These tracing will be transferred to the study team for analysis using a dedicated email.<br>|
| Low-Risk group<br>Montreal Heart Institute biobank participants with a low specific genome-wide polygenic risk scores for atrial fibrillation G | Diagnostic Test: Resting ECG (if first visit is done on site only)<br>* The standard 12-lead electrocardiogram is a representation of the heart's electrical activity recorded from electrodes on the body surface. This test requires around 15 minutes of the participant's time.<br>Diagnostic Test: 24-hour ambulatory electrocardiographic monitoring (Holter) (if first visit done on site only)<br>* The Holter monitor is a type of portable electrocardiogram (ECG) worn continuously for 24 hours.<br>Diagnostic Test: 3-month AF detection monitoring using the Apple Watch<br>* Patients with irregular heart rates will be notified by the Apple Watch and instructed to confirm the rhythm by using the integrated ECG recording system. This simply requires touching the watch with a finger from the opposite hand and provides a 30 seconds one-lead ECG recording of diagnostic quality. These tracing will be transferred to the study team for analysis using a dedicated email.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of atrial fibrillation/atrial flutter (Y/N) | Atrial Fibrillation will be diagnosed according to the standard definition: at least one 30-second recording with irregular rhythm without p waves. This will be accomplished either through the baseline ECG, Holter or during the 3 months monitoring with the Apple watch. The diagnostic of AF with the Apple watch requires: Detection of irregular heart rate (photopletysmography) Confirmation of the rhythm with a real time single lead 30 seconds ECG with the Apple Watch. | 3 months |