(Circulation. 1997;96:4298-4306.)
© 1997 American Heart Association, Inc.
Articles |
Antiarrhythmic Actions of Intravenous Ibutilide Compared With Procainamide During Human Atrial Flutter and Fibrillation
Electrophysiological Determinants of Enhanced Conversion Efficacy
From the West Roxbury Veterans Affairs Medical Center and Harvard Medical School (B.S.S.), West Roxbury, Mass, and the McGuire Veterans Affairs Medical Center and Medical College of Virginia (M.A.W., K.A.E.), Richmond, Va.
Correspondence to Bruce S. Stambler, MD, Cardiology Section (111A), West Roxbury VA Medical Center, 1400 VFW Pkwy, West Roxbury, MA 02132.
Background The selective class III antiarrhythmic agent ibutilide prolongs action potential duration and terminates atrial flutter (AFL) and fibrillation (AF), but the mechanism of its antiarrhythmic efficacy in humans has not been fully characterized. This study compared the antiarrhythmic effects of ibutilide with the class IA agent procainamide in humans during AFL and AF. Antiarrhythmic drug actions and electrophysiological characteristics of AFL and AF that enhanced pharmacological termination were investigated.
Methods and Results Right atrial monophasic action potentials
were recorded during 148 episodes of AFL (n=89) or AF (n=59) in 136
patients treated with intravenous ibutilide (n=73) or
placebo (n=22) as participants in randomized, double-blinded
comparative studies or intravenous procainamide
(n=53) in a concurrent open-label study. The conversion rates in AFL
with ibutilide, procainamide, and placebo were 64% (29 of 45
patients), 0% (0 of 33), and 0% (0 of 11), respectively, whereas in
AF the rates were 32% (9 of 28), 5% (1 of 20), and 0% (0 of 11),
respectively. In AFL, ibutilide increased atrial monophasic action
potential duration (MAPD) more (30% versus 18%, P<.001)
and prolonged atrial cycle length (CL) less (16% versus 26%,
P<.001) than procainamide. Ibutilide shortened and
procainamide prolonged action potential diastolic
interval during AFL (-12% versus 51%, P<.001). Ibutilide
increased MAPD/CL ratio, whereas procainamide tended to
decrease this ratio (13% versus -6%, P<.01). In AF,
ibutilide and procainamide induced similar increases in atrial
CL (48% versus 45%), but ibutilide induced a greater increase in MAPD
(52% versus 37%, P<.05). Independent
electrophysiological predictors of
pharmacological arrhythmia termination were increase in MAPD/CL
ratio (P=.005) in AFL and longer baseline mean MAPD
(P=.011) in AF. Termination of AFL with ibutilide was
characterized by significant increases in beat-to-beat atrial CL, MAPD,
and diastolic interval variability. Ibutilide was
significantly more effective in converting AF when the mean atrial CL
was 
160 ms (64% versus 0%, P<.001) or MAPD was 125 ms
(57% versus 0%, P=.002) at baseline.
Conclusions Enhanced conversion efficacy of ibutilide compared with procainamide in AFL is correlated with a relatively greater prolongation of atrial MAPD than atrial CL, and termination of AFL by ibutilide is characterized by oscillations in atrial CL and MAPD. Conversion of AF by ibutilide is enhanced by a longer baseline mean atrial CL or MAPD.
Key Words: antiarrhythmia agents • action potentials • fibrillation • electrophysiology
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|
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|
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|
|
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|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
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|
|
|
|
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|
|
|
|
|
|
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