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CLINICAL STUDY: ELECTROPHYSIOLOGY

Effect of metoprolol and d,l-sotalol on microvolt-level T-wave alternans

Results of a prospective, double-blind, randomized study

^a Department of Medicine, Division of Cardiology, J.W. Goethe University, Frankfurt, Germany

Manuscript received January 23, 2001; revised manuscript received August 21, 2001, accepted August 29, 2001.

^* Reprint requests and correspondence: Dr. Stefan H. Hohnloser, Department of Medicine, Division of Cardiology, J. W. Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany
Hohnloser{at}em.uni-frankfurt.de

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 µV vs. 8.5 ± 5.7 µV, p = NS). After drug administration, V_alt decreased by 35% with metoprolol (7.9 ± 6.0 µV to 4.9 ± 4.2 µV; p < 0.001) and by 38% with sotalol (8.6 ± 6.8 µV to 4.4 ± 2.3 µV; 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.

Abbreviations and Acronyms   CAD = coronary artery disease   ECG = electrocardiogram/electrogardiographic   EP = electrophysiologic   ERP = effective refractory period   ICD = implantable cardioverter-defibrillator   LVEF = left ventricular ejection fraction   RV = right ventricular   TWA = T-wave alternans   Valt = alternans voltage   VF = ventricular fibrillation   VT = ventricular tachycardia

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