Predictive Factors to Effectively Terminate Paroxysmal Atrial Fibrillation by Blocking Atrial Selective Ionic Currents

Overview

* 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.

* 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.