Acute effects of angiotensin II receptor blocker on ventricular repolarization alternans in chronic heart failure

Repolarization alternans, which can be detected clinically as microvolt-level T-wave alternans (TWA), is considered an important mechanism underlying the initiation of ventricular tachycardia/ventricular fibrillation (VT/VF) linked to sudden cardiac death (SCD). Recently, the rennin-angiotensin system (RAS) inhibitors have been suggested to have potential benefits in reducing SCD as well as heart failure death with chronic heart failure (CHF). In this study, we tested the acute effects of an angiotensin II receptor blocker (ARB), valsartan, on the development of TWA and the heart rate at which TWA appeared (onset heart rate; OHR). Fifty consecutive patients with CHF underwent TWA measurement. Patients with positive TWA were administered valsartan (80 mg/day) orally for 3 days. Alternans voltage in the vector magnitude lead (Valt) and the OHR were compared before and after the drug exposure. TWA was positive in 19 patients (38%), negative in 16 (32%), and indeterminate in 15 (30%). Nineteen patients with positive TWA received valsartan. However, 3 patients were withdrawn due to adverse drug reactions. In all the remaining 16 patients, markedly reduced Valt (6.1 +/- 3.8 microV to 2.5 +/- 1.9 microV; P = 0.002) and increased OHR (94 +/- 9 beats/min to 102 +/- 9 beats/min; p = 0.002) were observed. In particular, 3 patients became TWA negative. These results suggest that the RAS inhibitors prevent SCD by the improvement of repolarization abnormality.