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I read with great interest the outstanding historical review of long-QT and Brugada syndromes by Havakuk and Viskin (1). It was excellent. However, with respect to the section on “Evolution of Diagnostic Principles and Interpretation of Challenging Tests,” there is yet another part of the story relating to using potassium-channel blockers as a diagnostic challenge that the authors and the medical public do not know. It relates to ibutilide. Dr. Peter Kowey and I were among the investigators of ibutilide during the clinical trials that ultimately led to its approval for cardioversion of atrial fibrillation by the Food and Drug Administration in 1995. In those trials, all patients had 30-day follow-up visits, and detailed case report data was collected. Following their ibutilide dosing, some patients received oral antiarrhythmic drugs (AAD) to maintain sinus rhythm; many of these were class IA drugs. We proposed an analysis to the sponsor—specifically to look at the relationship between the presence/absence of torsade de pointes (TdP) occurring with ibutilide and the presence/absence of TdP with an oral class IA AAD. The hypothesis was that the absence of TdP with ibutilide would predict the absence of TdP with a subsequent class IA AAD. If true, then ibutilide could be used as a diagnostic stressor. If no TdP occurred, hospitalization for class IA AAD initiation could then be avoided with a significant reduction in medical costs and patient inconvenience. However, the sponsor (Pharmacia-Upjohn) did not want ibutilide to either be developed or used for this purpose and refused to let Dr. Kowey and I look at the 30-day database, despite our role as investigators for them. To my knowledge, this suggestion has never again been raised or examined, despite the fact that although class IA AAD are now only rarely used, both sotalol and dofetilide carry risk for TdP and the hypothesis may still be relevant and appropriate to investigate.
Please note: Dr. Reiffel has reported that he has no relationships relevant to the contents of this paper to disclose.
- 2016 American College of Cardiology Foundation