The diagnostic features of arrhythmic syndromes are often intermittent, subtle or absent on the resting ECG. Challenging or ‘stressing’ the dominant ion channel abnormality or the specific mechanism of the arrhythmia with pharmacologic agents can unmask the latent ECG abnormalities.
Epinephrine infusion has been used in the clinical evaluation of LQTS. Two infusion protocols have been developed — the epinephrine bolus followed by infusion and the graded epinephrine infusion. The latter is better tolerated and may be associated with lower incidence of false-positive responses. The graded epinephrine infusion is commenced at 0.05 µg//kg/min, doubling every 5 min to 0.2 µg/kg/min, and the QT interval is measured at each increment and at 5 and 10 min following the infusion. An absolute increase in QT interval of at least 30 ms at low dose epinephrine infusion (£ 0.1 µg/kg/min) is considered abnormal and provides a presumptive diagnosis of LQT1. Of note, the result of epinephrine challenge should not be inferred from exercise testing and vice versa, as epinephrine infusion results in greater QT shortening for a given increase in heart rate compared to exercise testing. Epinephrine infusion can also been used to unmask catecholaminergic polymorphic ventricular tachycardia.
Epinephrine infusion should be stopped in the event of raised systolic blood pressure over 200 mm Hg, non-sustained ventricular tachycardia or polymorphic ventricular tachycardia, frequent (> 10) premature ventricular contractions/minute, T-wave alternans, or patient intolerance. Appropriate resuscitation capabilities and training (and intravenous metoprolol) should be available despite the reported safety of epinephrine challenge.
Provocative pharmacological testing with intravenous class IC sodium channel blockers (ajmaline 1 mg/kg; flecainide 2 mg/kg, maximum 150 mg or procainamide 15 mg/kg, maximum 1 g depending on availability) is used to unmask or amplify the ST changes in patients with Brugada syndrome. The development of typical type 1 Brugada ECG pattern (≥ 2-mm J-point elevation and coved type ST-T segment elevation in leads V1 and V2) is considered positive. Monitoring should be continued until normalization of the ECG. Placing the precordial leads at higher intercostal space increases the sensitivity of detecting typical Brugada ECG pattern compared to conventional 12-lead ECG. Isoproterenol may be used to suppress ventricular arrhythmias in patients with Brugada syndrome.