THE GIRAFFE Study: Genomic Risk Markers for Atrial Fibrillation Following Extended Cardiac Rhythm Monitoring

NCT01970969 | Completed DMC

• 1 other identifier: 13-6159
• Study Type: observational
• Target: 928
• Locations: 1 country
• Sites: 1

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.

Conditions

Patients With Symptoms of Cardiac Arrhythmia at Risk for Atrial Fibrillation

Keywords

Atrial Fibrillation; Cardiac monitoring; Genomics

Outcome Measures

Primary Outcomes (1)

• Association between events of Atrial Fibrillation and 4-SNP risk score

  SNP effect sizes and frequencies were determined from the literature and the International HapMap Project database as indicated in Table 1. Expected occurrences of atrial fibrillation in the two groups were calculated using reference to previous studies as outlined above \[7, 8, 33\]. We expect 80 atrial fibrillation events in a 650 high-risk patients \[48, 49\]. Using these event rates and an alpha error of 5%, the power to detect an association between a 10-SNPs risk score and atrial fibrillation is \>90%. The power to detect association between a 4-SNP risk score and atrial fibrillation is \>80%.

  One time

Study Arms (1)

Cardiac arrhythmia symptoms

All subjects enrolled in the study will have an iRhythm Zio patch placed and a blood sample obtained.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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)\[46\].

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Scripps Translational Science Institute: lead
• Quest Diagnostics-Nichols Insitute: collaborator

Study Sites (1)

Scripps Clinic

La Jolla, California, 92037, United States

Location

Related Publications (1)

• 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.

  PMID: 29534064 DERIVED

Biospecimen

Retention: NONE RETAINED

A blood sample (in a 4 ml EDTA tube) for genotyping and a serum sample (in two 10ml red top tubes) will be obtained from each patient.

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Eric Topol, MD

  Scripps Translational Science Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2013
• First Posted: October 28, 2013
• Study Start: September 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2017
• Last Updated: April 17, 2018

Record last verified: 2018-04

Locations

US (1)