Brugada syndrome unmasked by lithium
ABSTRACT A 38-year-old man was brought by emergency medical service after resuscitation following cardiac arrest. The patient was found pulseless with a wide complex tachycardia. The patient had bipolar disorder and was on lithium, lamotrigine, and ziprasidone. His electrolytes and lithium levels were normal. An electrocardiogram (EKG) was performed the next day and showed type 1 Brugada pattern. Lithium was held. Electrophysiologists made a diagnosis of drug-unmasked Brugada syndrome. Lithium can unmask Brugada syndrome through its ability to block sodium channels, even at subtherapeutic concentrations. Physicians need to be aware of this potentially fatal drug effect and should monitor EKGs of patients on lithium.
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ABSTRACT: Drug-induced Brugada syndrome (BrS) represents a great challenge for the prescribing clinicians as well as for those involved in the development of novel pharmaceuticals and in the regulatory bodies responsible with monitoring drug safety. Apart from well-known cardiac agents (mainly Class I antiarrhythmics), an increasing number of noncardiac agents, including psychotropic and anesthetic drugs, have been shown to induce the characteristic Brugada electrocardiogram pattern predisposing to fatal ventricular arrhythmias. Up to now, both repolarization and depolarization abnormalities are thought to be related to the development of ventricular fibrillation in BrS patients. This review highlights the mechanisms and the noncardiac medical agents that unmask a genetic predisposition to BrS.Pacing and Clinical Electrophysiology 08/2013; DOI:10.1111/pace.12234 · 1.25 Impact Factor
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ABSTRACT: Identified genetic variants are insufficient to explain all cases of inherited arrhythmia. We tested whether the integration of whole exome sequencing with well-established clinical, translational, and basic science platforms could provide rapid and novel insight into human arrhythmia pathophysiology and disease treatment. We report a proband with recurrent ventricular fibrillation, resistant to standard therapeutic interventions. Using whole-exome sequencing, we identified a variant in a previously unidentified exon of the dipeptidyl aminopeptidase-like protein-6 (DPP6) gene. This variant is the first identified coding mutation in DPP6 and augments cardiac repolarizing current (Ito) causing pathological changes in Ito and action potential morphology. We designed a therapeutic regimen incorporating dalfampridine to target Ito. Dalfampridine, approved for multiple sclerosis, normalized the ECG and reduced arrhythmia burden in the proband by >90-fold. This was combined with cilostazol to accelerate the heart rate to minimize the reverse-rate dependence of augmented Ito. We describe a novel arrhythmia mechanism and therapeutic approach to ameliorate the disease. Specifically, we identify the first coding variant of DPP6 in human ventricular fibrillation. These findings illustrate the power of genetic approaches for the elucidation and treatment of disease when carefully integrated with clinical and basic/translational research teams. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.Journal of the American Heart Association 05/2015; 4(5):pii: e001762. DOI:10.1161/JAHA.114.001762 · 2.88 Impact Factor