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ST-segment Elevation as an AF Endophenotype (Proc)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01205529
Recruitment Status : Completed
First Posted : September 20, 2010
Results First Posted : May 2, 2018
Last Update Posted : May 2, 2018
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Dan Roden, 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).

Condition or disease Intervention/treatment Phase
Atrial Fibrillation Drug: Procainamide Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 161 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: All participants and investigators were blinded to the genetic sequencing results at the time of outcome ascertainment
Primary Purpose: Diagnostic
Official Title: ST-segment Elevation With Procainamide as an ECG Endophenotype of AF
Study Start Date : November 2010
Actual Primary Completion Date : June 2015
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  1. 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 [ Time Frame: 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01205529

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United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University Medical Center
National Heart, Lung, and Blood Institute (NHLBI)
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Principal Investigator: Dawood Darbar, MD, PhD Vanderbilt University

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Responsible Party: Dan Roden, Professor, Vanderbilt University Medical Center Identifier: NCT01205529    
Other Study ID Numbers: IRB # 100800
U19HL065962 ( U.S. NIH Grant/Contract )
First Posted: September 20, 2010    Key Record Dates
Results First Posted: May 2, 2018
Last Update Posted: May 2, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Dan Roden, Vanderbilt University Medical Center:
Atrial Fibrillation
ST elevation
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action