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FOCUS ISSUE: ATRIAL FIBRILLATION: CLINICAL RESEARCH: ATRIAL FIBRILLATION AND TORSADE

Persistent Atrial Fibrillation Is Associated With Reduced Risk of Torsades de Pointes in Patients With Drug-Induced Long QT Syndrome

Dawood Darbar, MD, FACC^_*,_*, John Kimbrough, MD, PhD^_*, Asif Jawaid^_*, Robert McCray, MD, Marylyn D. Ritchie, PhD and Dan M. Roden, MD, FACC^_*,

^_* Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.

Manuscript received July 31, 2007; revised manuscript received September 14, 2007, accepted September 19, 2007.

^_* Reprint requests and correspondence: Dr. Dawood Darbar, Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, 1285A MRB IV, 2311 Pierce Avenue, Nashville, Tennessee 37323-6602. (Email: dawood.darbar{at}vanderbilt.edu).

Objectives: The goal of this study was to identify markers of torsades de pointes (TdP) in patients with drug-associated long QT syndrome (LQTS).

Background: Drug-induced LQTS includes individuals developing marked prolongation of ventricular repolarization on exposure to an offending drug. Under these conditions, TdP develops in some but not all patients.

Methods: This was a case-control study of 123 adults with drug-associated LQTS. Patients were divided into LQTS only (LQTS; n = 40, QT >500 ms on drug) and LQTS + TdP (TdP; n = 83).

Results: Baseline QT intervals were similar in the 2 groups (381 ± 38 ms [LQTS] vs. 388 ± 43 ms [TdP]). Clinical variables associated with risk of TdP included hypokalemia and female gender; by contrast, persistent atrial fibrillation (AF) at the time of drug discontinuation for QT prolongation was protective despite similar heart rates in AF and sinus rhythm (n = 20, 71 ± 13 beats/min vs. 69 ± 13 beats/min). Electrocardiographic variables that significantly increased the risk for TdP included absolute and rate-corrected QT intervals (QTc) on drug therapy, the magnitude of QT and QTc interval prolongation, and the change in T_peak to T_end (T_p–T_e), a relatively new index of transmural dispersion of repolarization and potential arrhythmogenicity. Multivariable logistic regression analysis revealed that only gender was predictive for TdP, whereas persistent AF at the time of drug discontinuation for QT prolongation (odds ratio 0.14, 95% confidence interval 0.03 to 0.63, p = 0.01) was negatively associated with the arrhythmia.

Conclusions: This study strongly suggests that despite ongoing rate irregularity, AF reduces the likelihood of developing TdP after the administration of drugs that prolong cardiac repolarization.

Abbreviations and Acronyms   AF = atrial fibrillation   ECG = electrocardiogram   LQTS = long QT syndrome   SR = sinus rhythm   TdP = torsades de pointes   TDR = transmural dispersion of repolarization   Tp–Te = Tpeak to Tend

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J. Am. Coll. Cardiol. 2008 51: A23-A24. [Full Text] [PDF]