Predictive Factors to Effectively Terminate Paroxysmal Atrial Fibrillation by Blocking Atrial Selective Ionic Currents
Condition: Paroxysmal Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Study type: Interventional
Phase: Phase 4

Summary: 
      -  The main objective of this project is to study the efficacy and the mechanistic value of
           blocking both atrial specific and atria-preferential dynamics of ionic currents to
           terminate paroxysmal atrial fibrillation (AF).

        -  The hypothesis is that a drug blocking atrial specific and atria-preferential dynamics
           of ionic currents (IK,ACh - acetylcholine sensitive K+ current - and INa - inward sodium
           current - , respectively) will be more effective to terminate paroxysmal AF episodes
           with fast atrial activation rates, than a classical INa blocker, which will be more
           effective to terminate AF episodes with slower activation rates.

        -  The investigators will include patients without structural heart disease and
           short-lasting AF episodes (<48 h.). Double blind and single center study, in which
           patients will be randomly assigned to a cardioversion group using intravenous flecainide
           or to an atria-preferential and atrial-specific blockade group using intravenous
           vernakalant. Patients will be routinely monitored in the electrophysiology room to
           acquire both 12-lead digitized ECG signals and non-invasive body surface potential
           mapping. Atrial signals will be extracted from both the multisite body surface and ECG
           recordings to obtain temporal and spectral parameters, and measure organization and
           atrial rate in both groups. The results obtained in the clinical setting will be studied
           in mathematical models to understand their capability to terminate paroxysmal AF. The
           project expects to provide consistent, reliable and reproducible parameters that will
           assist clinicians to know what type of paroxysmal AF episodes will be more suitable to
           effectively terminate, upon administration of drugs with an atrial specific and
           atria-preferential profile.
    

Detailed description: 
      -  Background: Different research strategies aim at understanding the mechanisms underlying
           the maintenance of atrial fibrillation (AF), while preventing ventricular pro-arrhythmia
           related to the use of anti-arrhythmic drugs to restore sinus rhythm. Such aims might be
           achieved by drugs that effectively terminate reentrant sources identified during AF,
           along with an atrial specific and atria-preferential blockade of ionic currents. The
           latter may be especially relevant in paroxysmal AF episodes with fast atrial activation
           rates, in which INa and IK,ACh are involved in the maintenance of fast atrial reentrant
           sources underlying AF.

        -  Objective: The main objective of this project is to study the efficacy and the
           mechanistic value of blocking both atrial specific and atria-preferential dynamics of
           ionic currents to terminate paroxysmal AF.

        -  The hypothesis is that a drug blocking atrial specific and atria-preferential dynamics
           of ionic currents (IK,ACh and INa, respectively) will be more effective to terminate
           paroxysmal AF episodes with fast atrial activation rates, than a classical INa blocker,
           which will be more effective to terminate AF episodes with slower activation rates.

        -  Design: Double blind and single center study, in which patients will be randomly
           assigned to a cardioversion group using intravenous flecainide or to an
           atria-preferential and atrial-specific blockade group using intravenous vernakalant.
           Patients will be routinely monitored in the electrophysiology room for 90 minutes upon
           drug administration to acquire both 12-lead digitized ECG signals and non-invasive body
           surface potential mapping. Body surface recordings and conventional ECG signals will be
           exported to obtain temporal and spectral parameters of atrial activity during AF, and
           measure organization and atrial rate in both groups of patients undergoing
           pharmacological cardioversion. The success rate of cardioversion obtained in both groups
           will be correlated with the patterns of activation and spectral parameters obtained from
           the body surface, which will provide what type of paroxysmal AF episodes are suitable to
           terminate upon administration of anti-arrhythmic drugs with an atrial specific and
           atria-preferential profile.

      Electrical cardioversion will be performed in subjects with unsuccessful pharmacological
      cardioversion within the first 24 h. after vernakalant or flecainide administration.

      The results obtained in the clinical setting will be studied in realistic mathematical models
      to further understand the capability of both drugs to terminate paroxysmal AF.
    

Intervention name(s): Vernakalant; Flecainide
Intervention type(s): Drug; Drug
Intervention description(s): Initial infusion: 3 mg/kg intravenously over a 10 minute period. For patients weighing ≥ 113 kg, the maximum initial dose will be 339 mg. If conversion to sinus rhythm does not occur within 15 minutes after the end of the initial infusion, a second 10 minute infusion of 2 mg/kg will be administered. For patients weighing ≥ 113 kg, the maximum second infusion will be 226 mg.; 2 mg /kg (max 150 mg) intravenously over 10 minutes.
Other intervention name(s): BRINAVESS; APOCARD
Intervention MeSH terms: Flecainide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Atrial fibrillation; vernakalant; flecainide; cardioversion