Low dose disopyramide often fails to prevent neurogenic syncope during head-up tilt testing

Low dose disopyramide has been used to prevent neurally-mediated syncope during head-up tilt testing but a correlation between blood levels and efficacy has not been described. We measured disopyramide levels in 15 patients with recurrent syncope and positive 70 degrees head-up tilt tests who underwent one or more repeat tests on the drug. There were 9 males and 6 females, age range 15-78 years. Fourteen of the 15 patients had structurally normal hearts. The daily disopyramide dose was 645 +/- 165 mg (mean +/- SD). Patients developed syncope during 9 tests and had no syncope during 12 tests. The mean disopyramide level in patients with positive tests was significantly lower than the level in patients with negative tests (2.4 +/- 0.15 mu/mL vs 3.2 +/- 0.22 mu/mL, P = 0.018). Six patients were tested twice on different disopyramide doses. Five of these six patients had syncope during head-up tilt testing on the lower dose and negative tests on the higher dose (disopyramide levels 2.2 +/- 0.17 mu/mL vs 3.2 +/- 0.17 mu/mL, P = 0.004). Thus, disopyramide is effective in preventing neurogenic syncope during head-up tilt testing, but higher blood levels are often necessary for efficacy. In a given patient, failure to respond to low dose disopyramide does not preclude success on higher doses.