Effect of Metoprolol and D,l-sotalol on Microvolt-level T-wave Alternans. Results of a Prospective, Double-blind, Randomized Study

Objectives: The study evaluated the effects of metoprolol, a pure beta-blocker, and d,l-sotalol, a beta-blocker with additional class III antiarrhythmic effects, on microvolt-level T-wave alternans (TWA).

Background: Assessment of TWA is increasingly used for purposes of risk stratification in patients prone to sudden death. There are only sparse data regarding the effects of beta-blockers and antiarrhythmic drugs on TWA.

Methods: Patients with a history of documented or suspected malignant ventricular tachyarrhythmias were eligible. All patients underwent invasive electrophysiologic (EP) testing including programmed ventricular stimulation and determination of TWA at increasing heart rates using atrial pacing. Reproducibility of TWA at two consecutive drug-free baseline measurements was tested in a random patient subset. Following baseline measurements, all patients were randomized either to double-blind intravenous infusion of sotalol (1.0 mg/kg) or metoprolol (0.1 mg/kg). Results of TWA assessment at baseline and after drug exposure were compared.

Results: Fifty-four consecutive patients were studied. In 12 patients, repetitive baseline measurement of TWA revealed stable alternans voltage (V(alt)) values (9.1 +/- 5.8 microV vs. 8.5 +/- 5.7 microV, p = NS). After drug administration, V(alt) decreased by 35% with metoprolol (7.9 +/- 6.0 microV to 4.9 +/- 4.2 microV; p < 0.001) and by 38% with sotalol (8.6 +/- 6.8 microV to 4.4 +/- 2.3 microV; p = 0.001). In eight patients with positive TWA at baseline, repeated measurement revealed negative test results.

Conclusions: In patients prone to sudden cardiac death, there is a reduction in TWA amplitude following the administration of antiadrenergic drugs. This result indicates that TWA is responsive to the pharmacologic milieu and suggests that, to assess a patient's risk of spontaneous ventricular arrhythmia, the patient should be tested while maintaining the pharmacologic regimen under which the risk of arrhythmia is being assessed. This applies particularly for beta-blocker therapy.