Atrial Fibrillation
Conditions
Keywords
Atrial Fibrillation, ST elevation, Genotype
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.
Interventions
DRUGProcainamide
One time intravenous infusion of Procainamide administered over 30 minutes. Dosage is calculated as 10mg/kg based on subject's ideal body weight.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Vanderbilt University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Masking description
All participants and investigators were blinded to the genetic sequencing results at the time of outcome ascertainment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atrial Fibrillation With ST Changes on Electrocardiogram 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 also have SCN5A mutation.
Procainamide: One time intravenous infusion of Procainamide administered over 30 minutes. Dosage is calculated as 10mg/kg based on subject's ideal body weight. | 161 |
| Total | 161 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | No longer met criteria | 30 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Procedure Cancelled | 4 |
| Overall Study | Unstable post op | 15 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Atrial Fibrillation With ST Changes on Electrocardiogram |
|---|---|
| Age, Continuous | 55 years |
| Region of Enrollment United States | 161 participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 120 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 106 |
| serious Total, serious adverse events | 1 / 106 |
Outcome results
Primary
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
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.
Time frame: During (5, 10, 15, 20, 25, 30 minutes after initiating) or up to 15 minutes after completion of intravenous procainamide infusion
Population: Number of subject who had \>/= 1.5mm right precordial ST-segment elevation at baseline or with procainamide administration
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Atrial Fibrillation With ST Changes on Electrocardiogram | 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 | 4 Participants |
p-value: 1Regression, Logistic