ST-segment Elevation as an AF Endophenotype

Not Applicable

Completed

Conditions: Atrial Fibrillation

Interventions: Drug: Procainamide

Registration Number: NCT01205529

Lead Sponsor: Vanderbilt University Medical Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 161

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AF with ST changes on ECG	Procainamide	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.

Primary Outcome Measures

Name	Time	Method
ST Segment Elevation ≥ 1.5 mm in the Right Precordial Leads (V1-V3), Either at Baseline or Manifested After Sodium Channel Block With Intravenous Procainamide	During (5, 10, 15, 20, 25, 30 minutes after initiating) or up to 15 minutes after completion of intravenous procainamide infusion	Number of participants who demonstrated ST-segment elevation \>1.5mm in the right precordial leads (V1-V3) either at baseline or after sodium channel block with intravenous procainamide infusion.

Secondary Outcome Measures