A new drug is on horizon that may have a role in terminating atrial fibrillation (AF) and flutter (AFL).  This drug called ‘Vanoxerine’ was found to be successful in terminating induced AF and AFl in dogs according to matsumoto and colleagues form Cleveland. Vanoxerine is a dopamine transport antagonist that was initially developed as a possible therapy for Parkinson’s disease. Although the drug was not found to be clinically successful in treating Parkinsonism, it did have some desirable cardiac properties.

Prior studies had suggested that Vanoxerine can induce a rate dependent block of hERG, L-type calcium channels and sodium channels on the surface of myocardial cells. Despite being a more potent blocker of hERG channels compared to Class III anti-arrhythmic agents, it does not prolong action potential duration or QT interval.

To prove the role of this drug in AF and AFL, Matsumoto and colleagues used it on dogs in an experimental setting to see if its actions can simulate those of amiodarone in terminating AF and AFL. The AF and AFL episodes were induced in these dogs which were then studied with epicardial leads. After induction of arrhythmia, the dogs were started on intravenous Vanoxerine bolus followed by infusion that was continued for a minimum of 10 minutes until the termination of AF or AFL.

The researchers report that they induced 22 episodes of AF and AFL in nine dogs. Overall, there were 11 episodes of AFL, seven episodes of organized AF and 4 episodes of disorganized AF.  They were able to terminate 19 (86%) of them with Vanoxerine. The mean time to termination of Arrhythmias was 6.2 minutes (range 2-22) and median of 6.8 minutes. The author commented that Vanoxerine did not significantly alter the PR, QRS ot QTc durations.  Thus it is likely that Vanoxerine may not have as much proarrhythmic effects as most of the currently available anti-arrhythmics have.

The mechanism of action according to the study was prolonged cycle length of the drivers in case of AFl finally leading to disappearance of reentry of the driver. Disappearance of driver was also noted in organized AF thus suggesting similar mechanism. As the investigators could not map any stable drivers, they could not elucidate the possible mechanism in case of termination of disorganized AF. The authors also mentioned that the changes in conduction were seen in areas with slowed conduction with no affect elsewhere.

Current antiarrhythmics that can be used in management of AF and AFL are not the safest of drugs and the initial results form catheter ablation are still not optimal. If the results from this study can be reconfirmed again and the safety reproduced in human experiments, it may be a major breakthrough in management of AF and AFl.

References:

Matsumoto N, Khrestian CM, Ryu K, Lacerda AE, Brown AM, Waldo AL. Vanoxerine, a new drug for terminating atrial fibrillation and flutter. J Cardiovasc Electrophysiol. 2010 Mar;21(3):311-9.