Effects of tocainide on left ventricular performance at rest and during acute alterations in heart rate and systemic arterial pressure. An echocardiographic study.

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Abstract
A double blind cross-over trial of tocainimide, a new antiarrhythmic agent, and placebo in 10 patients with valvular heart disease was performed to determine if tocainimide depresses left ventricular function. Echocardiograms were recorded in the basal state, during atropine-induced increases in heart rate during acute pressure loading with phenylephrine. The drug doses were 400 mg every 8 h for 3 days, and the mean tocainide plasma concentration in the tocainide group was 5.3 .mu.g/ml. Heart rates and systolic blood pressures for both groups were closely matched during pharmacological interventions except after atropine when there was a slightly higher mean systolic blood pressure in the tocainide group (mean blood pressure difference 7 mmHg, P < 0.02). For the placebo and tocainide groups mean heart rates increased after atropine by 27 and 26 beats/min, respectively, and during infusion of phenylephrine (no significant heart rate slowing occurred) mean blood pressures rose by 51 mmHg in the placebo group (to 175 .+-. 6 mmHg) and by 45 mmHg in the tocainide group (to 176 .+-. 6 mmHg). During tocainide administration mean velocity of circumferential fibre shortening (mean VCF) in the basal state averaged 1.29 .+-. 0.06 diam(diameter)/s. This increased to 1.39 .+-. 0.08 diam/s with atropine and then declined to 1.17 .+-. 0.09 diam/s during infusion of phenylephrine (P < 0.01 vs atropine). No significant differences were found when the corresponding values during placebo were compared with these values. Similar directional changes occurred in the average mean posterior wall velocity (mean VPW) during tocainide administration when the corresponding values were 0.75 .+-. 0.05, 0.87 .+-. 0.07 (P < 0.05), and 0.71 .+-. 0.05 (P < 0.01 vs. atropine) s-1, respectively. Again placebo values did not differ significantly from tocainide values. In patients with valvular heart disease tocainide in the dose employed has no significant depressant effect on left ventricular function either in the basal state or during acute alterations in heart rate or blood pressure. Apparently tocainide can be used safely for antiarrhythmic therapy in patients with mild to moderate left ventricular dysfunction.