Possible Brugada Phenocopy Induced by Hypokalemia in a Patient with Congenital Hypokalemic Periodic Paralysis

Dear Editor,

We read with great interest the case report by Gazzoni et al¹ regarding a Brugada ECG pattern induced by hypokalemia. This paper is important because it contributes to the growing body of literature describing Brugada Phenocopies (BrP)^2-5.

Briefly, BrP are characterized by ECG patterns that are identical to type-1 or type-2 Brugada ECG patterns despite the absence of true congenital Brugada Syndrome (BrS). BrP are induced by various clinical circumstances including: hypokalemia, hyperkalemia, hypothermia, myocardial ischemia, and pulmonary embolism. We have established six etiological categories of BrP^2-4 along with a systematic approach to diagnose BrP³ by excluding sodium channel dysfunction in the myocardium. The presented case by Gazzoni et al¹ would possibly qualify under category (i) metabolic conditions; however, further analysis of this case report is required.

Specifically, this is the first report of a possible BrP induced by hypokalemia in association with hypokalemic periodic paralysis (HPP). Patients with HPP are known to have gene mutations resulting in abnormalities of either dihydropyridine sensitive calcium channels or sodium channels (SCN4A) in skeletal muscles. Patients with true congenital BrS have mutations in the myocardial sodium channels (SCN5A) and the association in this patient is most intriguing and remains speculative. The type-1 "coved" Brugada ECG pattern observed in this patient could have been induced by the transient serum hypokalemia (which would qualify this as a BrP) or there may be a congenital dysfunction in this patient's sodium channels in both his skeletal muscles (HPP) and myocardium resulting in the ECG abnormalities. Therefore, we recommend to the authors that a myocardial provocative challenge with a sodium channel blocker such as procainamide, ajmaline, or flecainide be performed to rule out myocardial sodium channel dysfunction. In addition, we also suggest that future reports use the established term Brugada Phenocopy to provide consistency in the literature and facilitate future research.

We are establishing an international registry database at www.burgadaphenocopy.com and invite Gazzoni et al¹ to submit this case along with future cases to the registry should they satisfy the BrP diagnostic criteria³. The goal of this registry is to provide long-term follow-up and insight into the pathophysiology and natural history of patients presenting with BrP.