Safety, Utility, and Outcomes of Procainamide Challenge for the Diagnosis and Exclusion of Brugada Syndrome

BACKGROUND: The safety, yield, and prognosis of a type 1 procainamide-induced Brugada pattern are incompletely understood and may differ from those of other sodium channel blockers with greater potencies. METHODS: The safety of procainamide infusion and yield of a type 1 Brugada pattern were assessed according to indication in consecutive patients from the Canadian Hearts in Rhythm Organization registry. Outcomes were evaluated in patients with a standard or high-lead procainamide-induced Brugada pattern (without previous cardiac arrest) and compared with those with a spontaneous type 1 pattern. RESULTS: In 947 consecutive patients undergoing procainamide infusion for the diagnosis or exclusion of Brugada syndrome, 2 patients (0.2%) experienced asymptomatic ventricular arrhythmias related to procainamide, which resolved upon discontinuation of the infusion. The yield of a type 1 pattern was 7.2% in 390 patients with unexplained cardiac arrest, 22.2% in 135 patients with a family history of Brugada syndrome, and 6.9% in 116 patients with a family history of unexplained cardiac arrest or sudden death. Test yield was 46.6% in 189 patients with a non-specific type 2 or 3 Brugada pattern and 92% in those with an intermittent spontaneous type 1 pattern (ie, implied sensitivity of 92%). Estimated specificity was very high. In 137 patients with a procainamide-induced type 1 Brugada pattern (with no previous cardiac arrest) followed for a mean of 5.9±4.5 years, no patients met the primary composite arrhythmic end point (0%). In 105 spontaneous type 1 patients, one patient (1%) met the primary end point after receiving appropriate shocks for ventricular fibrillation. Thirteen percent had a primary prevention implantable cardioverter defibrillator implanted at baseline (one appropriate shock), with an additional 7% undergoing implantable cardioverter defibrillator implantation during follow-up, predominantly for syncope with a suspected arrhythmic mechanism. No patient who underwent implantable cardioverter defibrillator implantation during follow-up subsequently received appropriate therapy. CONCLUSIONS: Procainamide infusion is extremely safe for the diagnosis and exclusion of Brugada syndrome, with yield dependent on pretest probability and indication for testing. Estimated sensitivity and specificity appear to be high. Patients with an asymptomatic procainamide-induced type 1 Brugada pattern are at very low risk of malignant ventricular arrhythmias.