Clinical trial NCT01970969: THE GIRAFFE Study: Genomic Risk Markers for Atrial Fibrillation Following Extended Cardiac Rhythm Monitoring
Official title: This Study Will Investigate the Association Between a Set of Single Nucleotide Polymorphisms (SNPs) and Atrial Fibrillation in Patients at High Risk of Developing Atrial Fibrillation. The SNPs Investigated Will Have Been Previously Shown to be Associated With the Atrial Fibrillation.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Patients With Symptoms of Cardiac Arrhythmia at Risk for Atrial Fibrillation
Keywords: Atrial Fibrillation
Cardiac monitoring
Genomics
Lead sponsor: Scripps Translational Science Institute
Sponsor class: OTHER
Collaborators: name: Quest Diagnostics-Nichols Insitute
First posted: 2013-10-28
Enrollment: 928
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients defined, as high risk for atrial fibrillation will be persons with:

1. No prior history of atrial fibrillation and/or atrial flutter (AFIB/AF) - with symptoms of high clinical suspicion for AFIB/AF prompting referral for ambulatory cardiac rhythm monitoring to evaluate for potential AFIB/AF, and
2. Any of the following features: ischemic stroke with no defined etiology (In prior 6 months) \[3, 4, 6, 7\], hypertension \[33\], increased body mass index (BMI \>30kg/m2) \[33\], heart failure \[33\], clinically significant murmur \[33\], prolonged PR interval on resting ECG (\>200msec) \[33\], chronic kidney disease \[34\], hypertrophic cardiomyopathy \[35\], congenital heart disease \[36\], chronic obstructive pulmonary disease \[37, 38\], sleep apnea \[39-41\], thyroid disease \[42, 43\], family history of atrial fibrillation \[44\], diabetes \[45\] or excess alcohol consumption (Male \> 14 drinks/week, Female \>7 drinks/week)\[46\].

Brief summary: Our primary hypothesis is that a risk score comprised of approximately 10 single nucleotide polymorphisms (SNPs) that are associated with atrial fibrillation at the Genome Wide Association Study (GWAS) level is associated with the development of atrial fibrillation among previously undiagnosed patients at high risk for atrial fibrillation. A current example of these SNPs is shown in Table 1. As a secondary hypothesis, we will test the association between atrial fibrillation diagnosed in this study with a subset of SNPs reported to be associated with atrial fibrillation and with fine-mapping SNPs. We will also test the association between atrial fibrillation of less than and greater than 30 seconds and a panel of approximately 10 SNPs.


Eligibility criteria: Inclusion Criteria:

* Symptoms of high clinical suspicion for atrial fibrillation prompting referral for ambulatory cardiac rhythm monitoring for potential atrial fibrillation.

AND

* At high risk for atrial fibrillation, defined as any one of the following: ischemic stroke with no defined etiology (In prior 6 months) \[3, 4, 6, 7\], hypertension \[33\], increased body mass index (BMI \>30kg/m2) \[33\], heart failure \[33\], clinically significant murmur \[33\], prolonged PR interval on resting ECG \[33\], chronic kidney disease \[34\], hypertrophic cardiomyopathy \[35\], congenital heart disease \[36\], chronic obstructive pulmonary disease \[37, 38\], sleep apnea \[39-41\], thyroid disease \[42, 43\], family history of atrial fibrillation \[44\], diabetes \[45\] or excess alcohol consumption (Male \> 14 drinks/week, Female \>7 drinks/week)\[46\].
* Age 40 years or older
* Capable of providing informed consent
* Capable of wearing a Zio Patch for up to 14 days
* Capable of providing a blood sample

Exclusion Criteria:

* Previously documented atrial fibrillation or atrial flutter.
* Prior cardiac surgery (coronary artery bypass grafting, valve replacement or repair, pericardial stripping, etc) within the past 30 days.
* Hyperthyroidism.
* Have known skin allergies, conditions, or sensitivities (e.g. allergy to adhesives, psoriasis) as the Zio Patch should not be used on patients with known skin allergies, conditions, or sensitivities.
* Are receiving pacing therapy.
* Are anticipated to receive or require external cardiac defibrillation during the monitoring period.
* Are anticipated to have exposure to high frequency surgical equipment during the monitoring period.

Primary outcomes:
measure: Association between events of Atrial Fibrillation and 4-SNP risk score
timeFrame: One time
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
Study officials:
affiliation: Scripps Translational Science Institute
name: Eric Topol, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Muse ED, Wineinger NE, Spencer EG, Peters M, Henderson R, Zhang Y, Barrett PM, Rivera SP, Wohlgemuth JG, Devlin JJ, Shiffman D, Topol EJ. Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study. PLoS Med. 2018 Mar 13;15(3):e1002525. doi: 10.1371/journal.pmed.1002525. eCollection 2018 Mar.