Clinical trial NCT04932798: Genetic Risk-Based Atrial Fibrillation Screening (GeneAF Study)
Official title: Genetic Risk-Based Atrial Fibrillation Screening
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Genetic Predisposition
Atrial Fibrillation
Lead sponsor: Montreal Heart Institute
Sponsor class: OTHER
First posted: 2021-06-21
Enrollment: 726
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All included subjects are current participants in the Montreal Heart Institute (MHI) biobank. Only candidates who would be considered for anticoagulation in case atrial firbrillation is detected (actionable AF; CHADS65 \> 1) will be considered for inclusion. MHI biobank participants that are eligible for the current study will be contacted to be part of the study.

Brief summary: 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: 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.

Eligibility criteria: 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:

1. Already on oral anticoagulation
2. Any prior history of AF or atrial flutter (AFl)
3. Patients currently having an implantable device (pacemaker, defibrillator or loop recorder) that allows detection of AF/AFl
4. Refusing testing with the "Apple Watch"

Primary outcomes:
measure: Detection of atrial fibrillation/atrial flutter (Y/N)
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Montreal Heart Institute
state: Quebec
Study officials:
affiliation: Montreal Heart Institute
name: Julia Cadrin-Tourigny, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, Natarajan P, Lander ES, Lubitz SA, Ellinor PT, Kathiresan S. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018 Sep;50(9):1219-1224. doi: 10.1038/s41588-018-0183-z. Epub 2018 Aug 13.
citation: Wunnemann F, Sin Lo K, Langford-Avelar A, Busseuil D, Dube MP, Tardif JC, Lettre G. Validation of Genome-Wide Polygenic Risk Scores for Coronary Artery Disease in French Canadians. Circ Genom Precis Med. 2019 Jun;12(6):e002481. doi: 10.1161/CIRCGEN.119.002481. Epub 2019 Jun 11.
citation: Perez MV, Mahaffey KW, Hedlin H, Rumsfeld JS, Garcia A, Ferris T, Balasubramanian V, Russo AM, Rajmane A, Cheung L, Hung G, Lee J, Kowey P, Talati N, Nag D, Gummidipundi SE, Beatty A, Hills MT, Desai S, Granger CB, Desai M, Turakhia MP; Apple Heart Study Investigators. Large-Scale Assessment of a Smartwatch to Identify Atrial Fibrillation. N Engl J Med. 2019 Nov 14;381(20):1909-1917. doi: 10.1056/NEJMoa1901183.