Activation of Inward Rectifier Potassium Channels Accelerates Atrial Fibrillation in Humans

Abstract

Background-It is unclear whether atrial fibrillation (AF) drivers in humans are focal or reentrant. To test the hypothesis that functional reentry is involved in human AF maintenance, we determined the effects of adenosine infusion on local dominant frequency (DF) at different atrial sites. By increasing inward rectifier potassium channel conductance, adenosine would increase DF of reentrant drivers but decrease it in the case of a focal mechanism. Methods and Results-Thirty-three patients were studied during AF (21 paroxysmal, 12 persistent) using recordings from each pulmonary vein-left atrial junction (PV-LAJ), high right atrium, and coronary sinus. DFs were determined during baseline and peak adenosine effect.

2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Patient Selection, Procedural Techniques, Patient Management and Follow-up, Definitions, Endpoints, and Research Trial Design

“…97 The response of PV activity to adenosine administration in patients with PAF is more consistent with a reentrant than a focalectopic type of mechanism. 98,99 In addition, dominant frequency analysis points to an evolution of mechanisms in patients with AF, with PV sources becoming less predominant as AF becomes more persistent and atrial remodeling progresses. 95 …”

Cardiac fibrillation: From ion channels to rotors in the human heart

“…A strong argument has been made that most patients with AF may have a focal mechanism as the initiating cause of the arrhythmia. 33 Yet reentry secondary to a wavebreak is by no means out of the question as an AF trigger. It is also likely that, in at least some AF patients, a rotor or small number of rotors are the drivers that maintain the arrhythmia.…”

“…45 This decrease of the response to ACh could also explain the reduced response to ADO observed in persistent AF in patients. 33 The increased basal agonist-independent current would result in rotor stabilization, acceleration of reentry, and spread of the DF sites from the PV to other non-PV locations and disappearance of LA to RA frequency gradients. Since antiarrhythmic drugs like amiodarone, flecainide, quinidine, and verapamil are also I K,ACh inhibitors, it cannot be ruled out that their therapeutic effectiveness results, at least partially, from inhibition of this constitutively active current in AF patients.…”

Gene Therapy for Cardiac Arrhythmias

“…Gap junctions such as connexin40 (Cx40) and connexin43 (Cx43) are designed to be another gene target for a rhythm control strategy, based on the idea that a slowed conduction velocity would be involved in the mechanism maintaining AF. 50 Bikou et al injected an adenovirus harboring Cx43 into a porcine atrium. 51 Treatment with Cx43 prevented AF events and tachycardia-induced cardiomyopathy.…”