Beta-blocker treatment guided by head-up tilt test in neurally mediated syncope

This study was an open-label, uncontrolled, dose-escalation trial of beta-blockers in patients with a history of syncope without warning or syncope resulting in trauma (malignant vasovagal syncope) who had positive head-up tilt test (HUT) responses, with or without isoproterenol infusion. Thirty patients (mean age, 37 +/- 21 years) with recurrent syncopal and near-syncopal episodes of unexplained origin in the previous year (6 +/- 14 syncopal episodes and 17 +/- 3 near-syncopes) underwent HUT for diagnostic purposes and for guiding prophylactic treatment. After patients were given a 10-minute rest in a recumbent position, rye performed an WT at 70 degrees for 25 minutes; if indicated, isoproterenol testing was performed at incremental dosages (dye steps at 10-minute intervals at 80 degrees), AU patients experienced syncope during HUT, 15 (50%) at baseline HUT and 15 (50%) during isoproterenol infusion (1 to 3 mu g/min; mean, 1.6 mu g/min). Sixteen syncopes were of vasodepressor type, 10 were mixed, and 4 were of cardioinhibitory type. After baseline HUT, betablocking drugs were prescribed to all patients as follows: 1 patient was given propranolol (160 mg daily), and 29 patients were given metoprolol (246 +/- 49 mg daily), with a dose titration period of 14 days. HUT was repeated after 3 weeks, and 24 patients (80%) had negative results (no syncope or anomalous responses). After further dosage adjustment of beta-blockers in nonresponders, a negative HUT was obtained in 28 patients (93%). Overall mean metoprolol daily dose was 262 +/- 60 mg (29 patients), and propranolol was administered at 160 mg daily in 1 patient. Thirteen patients (43%) reported side effects, none of which required drug withdrawal. At an average follow-up of 16 +/- 4 months, none of the patients experienced syncope, a statistically significant reduction. Moreover, a statistically significant reduction in the number of near-syncopal episodes was observed in comparison to the previous year. None of the patients discontinued treatment because of long-term side effects. Beta-blockers were well tolerated and achieved a high rate of efficacy, even in cardioinhibitory syncopes. In conclusion, in selected patients with malignant vasovagal syncope, treatment with metoprolol or propranolol at relatively high doses is feasible and, if guided by HUT results, is associated with a favorable outcome in terms of freedom from syncopal recurrences. Appropriate titration to achieve the full beta-blocking effect appears to be advisable.