Use, misuse, and pitfalls of the drug challenge test in the diagnosis of the Brugada syndrome

Figures

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  Figure 1. Schematic representation of the effects of genetic and environmental factors in Brugada syndrome. (A) Normal ST segment pattern in the right-precordial lead V1. (B) Acquired factors such as sodium channel blockers, fever, or increased vagal tonus or genetic factors act in a conjoint manner to reduce the depolarization reserve and delay electrical conduction in the right ventricular outflow tract, thereby leading to coved-type (Type 1) ST segment elevation in the right-precordial leads (here V1). SCB, sodium channel blocker.

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  Figure 2. Schematic representation of genetic and non-genetic determinants of Brugada syndrome. Shown are five distinct hypothetical patients with BrS and/or pathogenic SCN5A variants. The central mechanism underlying Brugada syndrome is a reduction in right ventricular outflow tract conduction reserve, mediated by any combination of the following: rare pathogenic SCN5A variant reducing sodium channel function, common genetic variants affecting sodium channel availability, exogenous sodium channel blockade, and other factors including fibrosis in the right ventricular outflow tract. The sodium channel blocker test consists in unmasking the Brugada syndrome phenotype in individual with underlying Brugada syndrome. The magnitude of each contributor to Brugada syndrome is schematically represented and does not necessarily reflect relative contributions which have not yet been quantified. BrS, Brugada syndrome; RVOT, right ventricular outflow tract.

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  Figure 3. Bubble plot. (A) Prognosis of asymptomatic patients. Red circles show occurrence of arrhythmic event in asymptomatic patients with spontaneous Type 1 electrocardiogram, and blue circles show that in asymptomatic patients without spontaneous Type 1 electrocardiogram. Bubble size represents the number of patients. Dotted lines show approximate line of the event ratio of each group. Patients with drug-induced Type 1 electrocardiogram had better prognosis (0.29%/year) than patients with spontaneous Type 1 electrocardiogram (0.88%/1year).34,56,69,76,81–86 The average event ratio was calculated from a formula of approximate line (asymptomatic spontaneous Type 1: y = 0.074 * 12 * x, asymptomatic drug-induced Type 1: y = 0.024 * 12 * x, x = follow-up months). (B) Prognosis of symptomatic patients including syncope and ventricular fibrillation/aborted cardiac arrest. Red circles represent symptomatic patients with spontaneous Type 1 electrocardiogram and blue circles show symptomatic patients without spontaneous Type 1 electrocardiogram. Patients with spontaneous Type 1 electrocardiogram had worse prognosis (4.08%/year) than patients with drug-induced Type 1 electrocardiogram…

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  Figure 4. Appropriateness of sodium channel blocker testing in common clinical scenarios. These appropriateness criteria for sodium channel blocker test are the authors’ expert opinion based on concerns regarding sodium channel blocker test specificity and the generally excellent prognosis of drug-induced Brugada syndrome in asymptomatic individuals, as discussed in text. BrS, Brugada syndrome; SCBT, sodium channel blocker test; VF, ventricular fibrillation; VT, ventricular tachycardia.