Dofetilide is more effective than
quinidine to terminate
atrial flutter in this animal model. It is also more capable of lengthening refractoriness more uniformly than
quinidine. While the investigators describe local changes in refractoriness and dispersion of refractoriness and wavelength meticulously, it is not clear which, if any, of these properties cause flutter termination or influence reinduction. This report provides new insight into the electrophysiologic mechanisms of
antiarrhythmic drugs used to treat atrial arrhythmias. Related investigations are needed to expand our knowledge of the actions of
antiarrhythmic drugs, how these drugs affect critical portions of the reentrant circuit, and how to identify potential adverse effects of these agents. Application of these data may help guide the use of
antiarrhythmic drugs and allow development of safer, and yet more potent, compounds. At least, it will give us pause about using more toxic and less effective drugs. While Class III drugs, specifically
dofetilide, may be more potent and beneficial than
quinidine in this model, it is uncertain that these results pertain to human reentrant atrial arrhythmias, particularly,
atrial flutter. Perhaps
dofetilide will be effective for certain types of
atrial flutter requiring an anatomical center defined by an area of injury or surgical
scar in the right atrium. The fact that these, and previous, data indicate a specific beneficial effect of
dofetilide, particularly on
atrial flutter, is interesting. Even if
dofetilide proves highly effective for human
atrial flutter, its safety will need to be proven in large clinical trials. The most obvious concern about
dofetilide is development of serious side effects such as
torsades de pointes. Clinical trials of this
drug for atrial arrhythmias are presently ongoing. Ultimately, the long-term use of such a
drug is dependent on the emergence of other highly effective
therapies such as
radiofrequency ablation.