Introduction: While predictors of drug-induced long QT syndrome (e.g., female gender, hypokalemia, drug interactions, and genetic factors) have been well-established, little is known about the clinical risk factors for drug-induced Brugada syndrome. In order to identify potential predictors of this life-threatening adverse event, we examined all published cases of Brugada syndrome induced by non-cardiac medications.
Methods: Reports of drug-induced Brugada syndrome recounted by an international database (http://www.brugadadrugs.org) were reviewed. The clinical and baseline electrocardiographic features of patients who developed this syndrome were analyzed.
Results: Overall, 61 cases of drug-induced Brugada syndrome caused by non-cardiac medications were identified. The most frequently reported agents were lithium and propofol (each accounting for 13% of the cases), cocaine (11%), and amitriptyline (10%). Over-dosage was involved in 48% of the cases. The majority of patients (84%) were of male gender, and the mean age was 40±17 years. Only 9% of the patients had prior history of syncope, and 7% had a family history of sudden death. By definition, type I Brugada pattern manifested in all cases during therapy with the culprit drug. In contrast, the ECG in the absence of offending drugs was normal in 66% of the cases and showed minor ECG abnormalities (including complete or incomplete right bundle branch block or an rSr’ pattern in leads V1-V2) in 20% of the cases. Importantly, in the absence of drugs, type II or type III Brugada pattern was observed in only 6% and 8% of the cases, respectively. In all but one case, drug-induced Brugada syndrome associated with oral medications occurred weeks to years after initiation of therapy.
Conclusions: Drug-induced Brugada syndrome related to non-cardiac drugs occurs predominantly in adult males and is frequently due to over-dosage. Importantly, the majority of patients with drug-induced Brugada-syndrome has a normal ECG at baseline and developed this complication late after therapy initiation. Consequently, neither ECG pre-screening, nor in-hospital monitoring, is likely to reduce the risk for drug-induced Brugada syndrome.
