Unmasking of Brugada Syndrome By Lithium
November 1, 2005 3 minutes read
Unmasking of Brugada Syndrome By Lithium
Abstract & Commentary
By John P. DiMarco, MD, PhD Dr. DiMarco is Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is a consultant for Novartis and does research for Medtronic and Guidant.
Synopsis: Lithium can unmask latent Brugada syndrome by blockade of susceptible cardiac sodium channels.
Source: Darbar D, et al. Unmasking of Brugada Syndrome By Lithium. Circulation. 2005;112:1527-1531.
Lithium is a drug frequently used to treat patients with bipolar disorder. In this paper, Darbar and colleagues describe 2 patients who developed electrocardiographic signs consistent with the Brugada syndrome and symptoms suggesting arrhythmia during treatment with lithium. Patient one was a 26-year-old man referred after classic type I Brugada syndrome ECG pattern (ST elevation with a right bundle branch block pattern in leads V1 to V3) was found after he had been begun on lithium. Prior electrocardiograms had not shown the Brugada syndrome pattern. The patient had a history of episodes of syncope or near syncope but had not had any previous electrocardiographic documentation of arrhythmia associated with these spells. Discontinuation of lithium led to partial resolution of the Brugada syndrome ECG pattern. Patient 2 was a 65-year-old man with manic depression who had been on lithium for many years. During this time, he reported episodes of recurrent syncope and after one syncopal episode showed a type I Brugada pattern again associated with classic ST segment elevation in V1 through V3. The patient had a family history of sudden death. A decrease in his lithium dose from 1200 mg per day to 400 mg per day normalized his electrocardiogram and he has remained asymptomatic on the lower dose of lithium.
To confirm the effects of lithium on the sodium channel, Darbar and colleagues studied the drug's effect on the cardiac sodium channel in Chinese hamster ovary cells expressing SCN5A. Peak sodium current was measured at various lithium concentrations. The IC50 for sodium current block by lithium was 6.8 ± 0.4 µmol/L. There was no effect on steady state inactivation or gating kinetics. Concentrations required for significant sodium channel inhibition were well below usual therapeutic levels.
Darbar et al conclude that lithium can unmask latent Brugada syndrome by blockade of susceptible cardiac sodium channels.
Commentary
Lithium is a commonly used drug in patients with bipolar disorders. Rarely, it causes sinus node suppression and severe bradycardia. Population surveys in patients with bipolar disorder, and also schizophrenia, have an increased sudden cardiac death rate. This has typically been attributed to the proarrhythmic effects of psychotropic drugs other than lithium used in these patients. The Brugada syndrome is a relatively uncommon condition that is thought to be due to an imbalance in action potential duration and configuration between the endocardium and epicardium, particularly in the right ventricle. A reduction in sodium current caused by drug mutations in SCN5A is one of the causes of this syndrome. In this paper, Darbar et al show that lithium unmasked latent Brugada syndrome in at least 2 susceptible individuals. Based on these observations, it would seem prudent to take a careful history for syncope or familial sudden death in patients about to begin lithium therapy. Particular care would be necessary in treating patients originally from southeast Asia where Brugada syndrome is prevalent. As with the use of many other psychotropic drugs, a follow-up electrocardiogram after therapy had been initiated, and certainly appears to be a reasonable precaution. The prevalence of the Brugada syndrome is so low in the general population that more restrictions on its use wouldn't be justified.
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