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(Circulation. 2005;112:1527-1531.)
© 2005 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Unmasking of Brugada Syndrome by Lithium

Dawood Darbar, MD; Tao Yang, MD, PhD; Keith Churchwell, MD; Arthur A.M. Wilde, MD, PhD; Dan M. Roden, MD

From the Divisions of Clinical Pharmacology (D.D., T.Y., D.M.R.) and Cardiovascular Medicine (D.D., K.C., D.M.R.), Vanderbilt University School of Medicine, Nashville, Tenn, and Cardiology Department (A.A.M.W.), Academic Medical Center, Amsterdam, the Netherlands.

Reprint requests to Dawood Darbar, MD, Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Room 383, Preston Research Bldg, Nashville, TN 37232-6602. E-mail dawood.darbar{at}vanderbilt.edu

Received March 10, 2005; revision received June 7, 2005; accepted June 21, 2005.

Background— The characteristic ECG pattern of ST-segment elevation in V₁ and V₂ in the Brugada syndrome is dynamic; it is often intermittently present in affected individuals and can be unmasked by sodium channel blockers, including antiarrhythmic drugs and tricyclic antidepressants. We report here 2 patients who developed the Brugada ECG pattern after administration of lithium, a commonly used drug not previously reported to block cardiac sodium channels.

Methods and Results— Lithium induced transient ST-segment elevation (type 1 Brugada pattern) in right precordial leads at therapeutic concentrations in 2 patients with bipolar disorder. Lithium withdrawal in the patients resulted in reversion to type 2 or 3 Brugada patterns or resolution of ST-T abnormalities. In Chinese hamster ovary cells transfected with SCN5A, which encodes the cardiac sodium channel, lithium chloride caused concentration-dependent block of peak I_Na at levels well below the therapeutic range (IC₅₀ of 6.8±0.4 µmol/L).

Conclusions— The widely used drug lithium is a potent blocker of cardiac sodium channels and may unmask patients with the Brugada syndrome.

Key Words: Brugada syndrome • lithium • drugs • genetics • ion channels

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