ST-segment Elevation as an AF Endophenotype

NCT ID: NCT01205529

Last Updated: 2018-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 161 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2015-06-30

Brief Summary

The purpose of this study is to look for a similarity in people's genes that may help understand which people could benefit from certain drugs for the treatment of atrial fibrillation (AF).

Detailed Description

Current drug therapies to suppress AF are incompletely and unpredictably effective and carry significant (albeit generally small) risks of serious adverse effects, including drug-induced long QT syndrome (diLQTS), other forms of proarrhythmia, increased mortality through uncertain mechanisms, and extracardiac toxicity. Identification of clinical and genetic subtypes of AF will permit stratification of therapeutic approaches and thereby facilitate the practice of personalized medicine. Furthermore, limited success of drug therapy and increase in drug toxicity in AF is probably because the arrhythmia represents a final common pathway of multiple initiating mechanisms, including some that are genetically-defined.

Identifying specific intermediate phenotypes ("endophenotypes") associated with defined clinical courses in AF represents a potential method to systematically subtype patients by underlying mechanism and represents a much-needed clinical advance. Clinical endophenotypes that have been studied include atrial fibrillatory rate, prolonged signal-averaged P-wave duration, and biomarker profiles. The endophenotype we will study here is right precordial ST segment elevation, seen not only in Brugada syndrome (BrS) (where it is unmasked by sodium channel blocking drugs) but also commonly in early-onset ('lone') AF and in patients with AF-associated rare variants in genes encoding the cardiac sodium channel α- or β-subunits. Taken together these data suggest the hypothesis to be tested in this study, that variants in multiple genes can culminate in a similar AF-prone substrate by reducing sodium current that can be identified by screening for baseline or manifest right precordial ST segment elevation endophenotype after sodium channel block with intravenous procainamide.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

AF with ST changes on ECG

Those patients with ST segment or J Point elevation on electrocardiogram. Can be on initial screening electrocardiogram or on electrocardiograms during procainamide infusion. These subjects will harbor cardiac sodium channel gene variants.

Group Type: OTHER

Procainamide

Intervention Type: DRUG

One time intravenous infusion of Procainamide administered over 30 minutes. Dosage is calculated as 10mg/kg based on subject's ideal body weight.

Interventions

Procainamide

One time intravenous infusion of Procainamide administered over 30 minutes. Dosage is calculated as 10mg/kg based on subject's ideal body weight.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 18 years of age or older
• Undergoing AF ablation at Vanderbilt or MGH

Exclusion Criteria

• Patients taking membrane active anti-arrhythmic drugs with sodium channel blocking properties (amiodarone, dronedarone, flecainide, propafenone) at the time of the ablation
• Patients with a history of Brugada syndrome or type 1 Brugada ECG pattern on the baseline ECG
• Patients with a history of drug-induced torsades de pointes
• Patients with a known history of hypersensitivity to procainamide, procaine or related drugs
• Patients with a history of systemic lupus erythematosus and myasthenia gravis
• Patients with a history of second degree AV block (Mobitz type II) or third degree AV block
• Women of child-bearing potential unless post-menopausal, surgically sterile, or have a negative pregnancy test day on the day of procedure
• Patients with dual chamber pacemakers or implantable defibrillators requiring ventricular pacing (uninterpretable ECG)
• Patients unable to give informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Dan Roden

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dawood Darbar, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

U19HL065962

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB # 100800

Identifier Type: -

Identifier Source: org_study_id