Elsevier

Heart Rhythm

Volume 13, Issue 5, May 2016, Pages 1083-1087
Heart Rhythm

Drug-induced Brugada syndrome: Clinical characteristics and risk factors

https://doi.org/10.1016/j.hrthm.2016.03.016Get rights and content

Background

Cardiac arrest may result from seemingly innocuous medications that do not necessarily have cardiac indications. The best-known example is the drug-induced long QT syndrome. A less known but not necessarily less important form of drug-induced proarrhythmia is the drug-induced Brugada syndrome.

Objective

The purpose of this study was to identify clinical and ECG risk markers for drug-induced Brugada syndrome.

Methods

Reports of drug-induced Brugada syndrome recounted by an international database (http://www.brugadadrugs.org) were reviewed to define characteristics that identify patients prone to developing this complication. For each patient with drug-induced Brugada syndrome who had an ECG recorded in the absence of drugs, we included 5 healthy controls matched by gender and age. All ECGs were evaluated for Brugada-like abnormalities.

Results

Seventy-four cases of drug-induced Brugada syndrome from noncardiac medications were identified: 77% were male, and drug toxicity was involved in 46%. Drug-induced Brugada syndrome from oral medications generally occurred weeks after the initiation of therapy. Mortality was 13%. By definition, all cases had a type I Brugada pattern during drug therapy. Nevertheless, their ECG in the absence of drugs was more frequently abnormal than the ECG of controls (56% vs 33%, P = .04).

Conclusion

Drug-induced Brugada syndrome from noncardiac drugs occurs predominantly in adult males, is frequently due to drug toxicity, and occurs late after the onset of therapy. Minor changes are frequently noticeable on baseline ECG, but screening is impractical because of a prohibitive false-positive rate.

Section snippets

Methods

The website http://www.BrugadaDrugs.org has up-to-date and free access to a consensus statement on the safe use of drugs in Brugada syndrome.9 At initiation of the website in 2009, an extensive literature review was performed on published associations between drugs and Brugada syndrome.9 An advisory board of experts periodically reviews up-to-date information collected during weekly literature searches. The advisory board labels drugs as “drugs to be avoided” or “drugs preferably avoided.” The

Results

We identified 74 cases of Brugada syndrome induced by 27 noncardiac drugs in 62 reports (see Online Supplementary Material for references). Among these cases, 36 (49%) were induced by psychotropic drugs, 20 (27%) were induced by analgesic–anesthetic drugs, and 18 (24%) were induced by other noncardiac drugs. The most frequently reported agent was intravenous propofol, which accounted for 20% of cases. The most frequently reported oral agents were lithium and amitriptyline (accounting for 20%

Discussion

Drug-induced LQTS was first recognized half a century ago, whereas drug-induced Brugada syndrome was recognized only recently.19 This does not make drug-induced Brugada syndrome any less important.9 In fact, long-term use of nortriptyline (an antidepressant that blocks the cardiac sodium channel) is associated with a 5-fold increased risk of sudden death,20 probably caused, at least in part, by drug-induced Brugada syndrome.20 Thus, better characterization of this phenomenon is needed. With

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