547
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Brugada Phenocopy with a Flecainide Overdose: A Pharmacological Dose Effect? HENRY CHUBB, M.B.B.S.,∗ MICHAEL COOKLIN, M.D.,† and ERIC ROSENTHAL, M.D.∗ From the ∗ Department of Paediatric Cardiology, Evelina London Children’s Hospital, Guy’s & St Thomas NHS Foundation Trust, London, UK; and †Department of Cardiology, St Thomas’ Hospital, London, UK
A 13-year-old girl attended the emergency department after an overdose of flecainide (1.25 g) and bisoprolol (30 mg). She was previously well, with no history of syncope, normal echocardiographic findings, and no family history of sudden death. Her first ECG in the presence of supratherapeutic flecainide levels demonstrated the “unmasking” of a Brugada pattern (Fig. 1A). Following this, she developed gross QRS broadening, polymorphic ventricular tachycardia, and intermittent complete heart block during the peak flecainide levels (Fig. 1B) requiring temporary transvenous pacing. The J Cardiovasc Electrophysiol, Vol. 25, pp. 547-548, May 2014. No disclosures. Address for correspondence: Eric Rosenthal, M.D., Department of Paediatric Cardiology, Evelina London Children’s Hospital, Guy’s & St Thomas NHS Foundation Trust, London, SE1 7EH, UK. Fax: 020 7188 4556; E-mail: [email protected] doi: 10.1111/jce.12335
Brugada pattern re-emerged at lower (yet still supratherapeutic levels) before returning to the normal baseline (Figs. 1C–E). Flecainide is a Class 1C sodium channel blocker that has been used to unmask concealed forms of Brugada syndrome. The drug level at which the Brugada pattern was found in this patient was approximately 1,500–2,000 ng/mL. By comparison, the serum flecainide level achieved 10 minutes after an intravenous loading dose of flecainide (2 mg/kg over 5–10 minutes) has been shown to be 825 ± 294 ng/mL. The Brugada pattern was provoked in the absence of channelopathy or structural heart disease. Little is known about the positive predictive value of a Brugada pattern caused by supratherapeutic levels of Class 1C drugs, and Brugada phenocopy in flecainide toxicity has been reported previously in a patient with atrial fibrillation. However, this case provides a unique insight into the dose effect of flecainide in the apparently normal child, with a phenocopy zone at supratherapeutic levels. Formal pharmacokinetic studies correlating drug levels with ECG changes are therefore needed to clarify the meaning of Brugada challenge testing.
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Journal of Cardiovascular Electrophysiology
Vol. 25, No. 5, May 2014
Figure 1. Electrocardiograms recorded at (A) 6 hours after the overdose, (B) 11 hours, (C) 15 hours (D), 36 hours, and (E) 180 hours. Graph demonstrates the recorded flecainide levels in ng/mL, with vertical lines indicating the point at which the respective electrocardiograms were recorded. (A) and (C) demonstrate a type 1 Brugada pattern, with an initial ST elevation of >2 mm and a slowly descending ST–T segment. (B) shows the development of a broad QRS complex, with intermittent heartblock and ventricular tachycardia. The Brugada pattern recurred as the flecainide levels fell, and began to resolve at 36 hours (D). The resting ECG was normal prior to discharge (E). For a high quality, full color version of this figure, please see Journal of Cardiovascular Electrophysiology’s website: www.wileyonlinelibrary.com/journal/jce
EP Image
Brugada Phenocopy with a Flecainide Overdose: A Pharmacological Dose Effect? HENRY CHUBB, M.B.B.S.,∗ MICHAEL COOKLIN, M.D.,† and ERIC ROSENTHAL, M.D.∗ From the ∗ Department of Paediatric Cardiology, Evelina London Children’s Hospital, Guy’s & St Thomas NHS Foundation Trust, London, UK; and †Department of Cardiology, St Thomas’ Hospital, London, UK
A 13-year-old girl attended the emergency department after an overdose of flecainide (1.25 g) and bisoprolol (30 mg). She was previously well, with no history of syncope, normal echocardiographic findings, and no family history of sudden death. Her first ECG in the presence of supratherapeutic flecainide levels demonstrated the “unmasking” of a Brugada pattern (Fig. 1A). Following this, she developed gross QRS broadening, polymorphic ventricular tachycardia, and intermittent complete heart block during the peak flecainide levels (Fig. 1B) requiring temporary transvenous pacing. The J Cardiovasc Electrophysiol, Vol. 25, pp. 547-548, May 2014. No disclosures. Address for correspondence: Eric Rosenthal, M.D., Department of Paediatric Cardiology, Evelina London Children’s Hospital, Guy’s & St Thomas NHS Foundation Trust, London, SE1 7EH, UK. Fax: 020 7188 4556; E-mail: [email protected] doi: 10.1111/jce.12335
Brugada pattern re-emerged at lower (yet still supratherapeutic levels) before returning to the normal baseline (Figs. 1C–E). Flecainide is a Class 1C sodium channel blocker that has been used to unmask concealed forms of Brugada syndrome. The drug level at which the Brugada pattern was found in this patient was approximately 1,500–2,000 ng/mL. By comparison, the serum flecainide level achieved 10 minutes after an intravenous loading dose of flecainide (2 mg/kg over 5–10 minutes) has been shown to be 825 ± 294 ng/mL. The Brugada pattern was provoked in the absence of channelopathy or structural heart disease. Little is known about the positive predictive value of a Brugada pattern caused by supratherapeutic levels of Class 1C drugs, and Brugada phenocopy in flecainide toxicity has been reported previously in a patient with atrial fibrillation. However, this case provides a unique insight into the dose effect of flecainide in the apparently normal child, with a phenocopy zone at supratherapeutic levels. Formal pharmacokinetic studies correlating drug levels with ECG changes are therefore needed to clarify the meaning of Brugada challenge testing.
548
Journal of Cardiovascular Electrophysiology
Vol. 25, No. 5, May 2014
Figure 1. Electrocardiograms recorded at (A) 6 hours after the overdose, (B) 11 hours, (C) 15 hours (D), 36 hours, and (E) 180 hours. Graph demonstrates the recorded flecainide levels in ng/mL, with vertical lines indicating the point at which the respective electrocardiograms were recorded. (A) and (C) demonstrate a type 1 Brugada pattern, with an initial ST elevation of >2 mm and a slowly descending ST–T segment. (B) shows the development of a broad QRS complex, with intermittent heartblock and ventricular tachycardia. The Brugada pattern recurred as the flecainide levels fell, and began to resolve at 36 hours (D). The resting ECG was normal prior to discharge (E). For a high quality, full color version of this figure, please see Journal of Cardiovascular Electrophysiology’s website: www.wileyonlinelibrary.com/journal/jce
