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CLINICAL STUDIES

Exaggerated QT prolongation after cardioversion of atrial fibrillation

^a Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
^b Department of Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

Manuscript received July 28, 1998; revised manuscript received March 19, 1999, accepted April 23, 1999.

Reprint requests and correspondence: Dr. Dan M. Roden, Professor of Medicine and Pharmacology, Vanderbilt University, 532C Medical Research Building I, Nashville, Tennessee 37232-6602
dan.roden{at}mcmail.vanderbilt.edu

OBJECTIVES

The purpose of this study was to test the hypothesis that the extent of drug-induced QT prolongation by dofetilide is greater in sinus rhythm (SR) after cardioversion compared with during atrial fibrillation (AF).

BACKGROUND

Anecdotes suggest that when action potential–prolonging antiarrhythmic drugs are used for AF, excessive QT prolongation and torsades de pointes (TdP) often occur shortly after sinus rhythm is restored.

METHODS

QT was measured in nine patients with AF who received two identical infusions of dofetilide: 1) before elective direct current cardioversion and 2) within 24 h of restoration of SR.

RESULTS

During AF, dofetilide did not prolong QT (baseline: 368 ± 48 ms vs. drug: 391 ± 60, p = NS) whereas during SR, QT was prolonged from 405 ± 55 to 470 ± 67 ms (p < 0.01). In four patients (group I), the SR dofetilide infusion was terminated early because QT prolonged to >500 ms, and one patient developed asymptomatic nonsustained TdP. The remaining five patients (group II) received the entire dose during SR. Although QT was greater in group I during SR (91 ± 22 vs. 45 ± 25 ms, p < 0.05), plasma dofetilide concentrations during SR were similar in the two groups (2.72 ± 0.96 vs. 2.77 ± 0.25 ng/ml), and in AF (2.76 ± 1.22 ng/ml). QT in SR correlated inversely with baseline SR heart rate (r = –0.69, p < 0.05), and QT dispersion developing during the infusion (r = 0.79, p < 0.01).

CONCLUSIONS

Shortly after restoration of SR, there was increased sensitivity to QT prolongation by this I_Kr-specific blocker. Slower heart rates after cardioversion and QT dispersion during treatment appear to be important predictors of this response.

Abbreviations and Acronyms   AF = atrial fibrillation   ANP = atrial natriuretic peptide   ECG = electrocardiographic/electrocardiogram   QTd = QT dispersion   SR = sinus rhythm   TdP = torsades de pointes

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