Efficacy of intravenous ibutilide for rapid termination of atrial fibrillation and atrial flutter: A dose-response study

Ellenbogen, Kenneth A.; Stambler, Bruce S.; Wood, Mark A.; Sager, Philip T.; Wesley, Robert C.; Meissner, Marc D.; Zoble, Robert G.; Wakefield, Linda K.; Perry, Kimberly T.; Vanderlugtt, James T.; Investigators, Ibutilide

doi:10.1016/0735-1097(96)00121-0

Cited by 344 publications

(196 citation statements)

References 17 publications

Supporting

Mentioning

178

Contrasting

Unclassified

Order By: Relevance

“…For these drugs, available evidence indicates that both torsades risk and QT interval prolongation by the drugs are doserelated. [6][7][8] While these relationships speak to links among drug dose, I Kr block, QT prolongation, and torsades risk, they should not be over-interpreted. Specifically, it is clear that the extent of arrhythmia risk with a given drug dose or degree of QT prolongation varies among individuals, reflecting both known factors such as comedications, pauses, or underlying rhythm 9 as well as undetermined factors, including possible genetic contributors.…”

Section: Variable Arrhythmogenic Potential Of Qt Prolongationmentioning

confidence: 99%

Keep the QT interval: It is a reliable predictor of ventricular arrhythmias

Roden

2008

Heart Rhythm

View full text Add to dashboard Cite

The cardiovascular community understands that the QT interval is the surface electrocardiographic representation of ventricular repolarization. However, despite tremendous advances in our understanding of the molecular and cellular basis for cardiac repolarization and its surface ECG representation, clinicians, regulators, and drug developers are increasingly faced with uncertainty over the best way to interpret this parameter. The evidence described below demonstrates that• Prolongation of the QT interval is a reliable predictor of ventricular arrhythmias in some settings, and may be less predictable in others• The arrhythmogenic potential of a given degree of QT prolongation varies among individuals and drugs. Further, the relationship between QT prolongation and arrhythmia susceptibility is non-linear. Multiple mechanisms may underlie QT prolongation, and these may carry different arrhythmogenic potential.• There is little doubt that further understanding of the cellular and molecular mechanisms underlying repolarization hold the promise of developing better indices of the arrhythmogenic potential of abnormalities of repolarization, but that science has not yet matured A caveat: The QT interval is hard to measureMeasuring the QT is hard enough when it is normal, and it is almost impossible to come up with a workable number in the face of common disease-associated ECG changes such as diffuse ST segment changes, inverted T-waves, small or large U-waves, or pauses (see Figure 1). A second problem is rate: while there is absolutely no doubt that action potential durations in ventricular tissue, and the QT interval, are exquisitely dependent on previous cycle length or cycle lengths, the "best" method to correct for rate, and thus allow QT intervals recorded at different rates to be compared, is not known. Indeed, comparing two "rate-corrected" QT values presupposes that whatever the intervention between the two recordings -often a drug -itself has no effect on rate. Further, even if a drug has no direct effect on rate, common conditions for which drugs are prescribed may be associated with increases in heart rate (e.g. due to fever or to autonomic activation); any effective drug may thus affect heart rate indirectly.

show abstract

Section: Variable Arrhythmogenic Potential Of Qt Prolongationmentioning

confidence: 99%

Keep the QT interval: It is a reliable predictor of ventricular arrhythmias

Roden

2008

Heart Rhythm

View full text Add to dashboard Cite

show abstract

“…1 Ibutilide significantly prolonged the rate-corrected QT (QTc) interval in electrocardiographic (ECG) studies in healthy volunteers and patients with AF or AFl. [2][3][4][5] This effect was dose related and correlated directly with plasma ibutilide concentrations. 3 The QTc interval reflects the duration of repolarization of the ventricles, and its prolongation is indicative of class III antiarrhythmic activity.…”

Section: Introductionmentioning

confidence: 99%

“…It prolongs the action potential duration and effective refractory periods in both the atria and the ventricles. [1][2][3][4][5] In previous studies, ibutilide significantly prolonged the QTc interval in ECG studies in healthy volunteers and patients with AF or AFl. [2][3][4][5] This effect was dose related and correlated directly with plasma ibutilide concentrations.…”

Section: Ibutilide-induced Repolarization Alterationsmentioning

confidence: 99%

“…[1][2][3][4][5] In previous studies, ibutilide significantly prolonged the QTc interval in ECG studies in healthy volunteers and patients with AF or AFl. [2][3][4][5] This effect was dose related and correlated directly with plasma ibutilide concentrations. 3 In this study, although QT maximum, QT minimum, and QT dispersion significantly increased from baseline to the postinfusion ECG in Group 1 patients, QTc maximum failed to demonstrate significant changes from the first to the second ECG.…”

Section: Ibutilide-induced Repolarization Alterationsmentioning

confidence: 99%

See 1 more Smart Citation

Ibutilide‐induced alterations in electrocardiographic and spatial vectorcardiographic descriptors of ventricular repolarization

Dilaveris

Theoharis

Giaouris

et al. 2004

Clinical Cardiology

View full text Add to dashboard Cite

SummaryBackground: Ibutilide is used for the pharmacologic cardioversion of atrial fibrillation (AF) or flutter (AFl). Ibutilideinduced QT interval prolongation has been demonstrated previously. However, its effects on vectorcardiographic (VCG) descriptors of ventricular repolarization (VR) have not been studied so far.Hypothesis: To evaluate the effects of ibutilide on electrocardiographic (ECG) and VCG descriptors of VR, one or two repeated 10-min infusions of 1 mg of ibutilide were given in 50 consecutively recruited patients (36 women, mean age 69.4 ± 9.3 years) with AF or AFl of recent onset.Methods: The maximum and the minimum QT intervals, QT dispersion, the rate-corrected QT maximum, and the spatial VCG descriptors, spatial T amplitude, and spatial QRS-T angle were calculated before (baseline ECG) and 30 min after the start of ibutilide infusion (postinfusion ECG).Results: After ibutilide infusion, 40 (80%) patients were cardioverted to sinus rhythm (Group 1), while in the remaining 10 (Group 2) AF or AFl persisted. In both study groups, temporal measures of VR were significantly increased from baseline to the postinfusion ECG. In Group 1, spatial T amplitude and spatial QRS-T angle did not differ between those two ECGs, while in Group 2 spatial T amplitude was significantly increased (p = 0.005) and spatial QRS-T angle was significantly decreased (p = 0.002) post infusion compared with baseline ECG.Conclusions: While temporal measures of VR are significantly affected in all patients who receive ibutilide infusion for AF or AFl cardioversion, spatial VCG descriptors of VR are

show abstract

“…The resultant Survival With Oral d-Sotalol (SWORD) trial, 12 in which mortality in the d-sotalol-treatment group was excessive, not only mirrored the CAST experience for a different patient population but further dampened the enthusiasm for new antiarrhythmic drug development. Nonetheless, some apparently useful drugs (eg, dofetilide, 13 ibutilide, 14 and azimilide 15 ) have evolved from the effort to prolong repolarization and, in some instances, have been approved for patient care.…”

Section: See P 1288mentioning

confidence: 99%