Amiloride. Antiarrhythmic and electrophysiologic actions in patients with inducible sustained ventricular tachycardia.
This study assessed the antiarrhythmic activity of amiloride in 35 patients with inducible sustained ventricular tachycardia. Patients had failed to respond to 3.6 +/- 1.0 antiarrhythmic drugs. Ventricular tachycardia was reproducibly induced by programmed electrical stimulation in all patients at the baseline study. Amiloride was given at 10 and 20 mg/day p.o. on a twice-daily schedule that achieved serum concentrations of 21 +/- 17 and 36 +/- 18 ng/ml, respectively. The mean left ventricular ejection fraction was unchanged from 36 +/- 14% at baseline to 37 +/- 17% during amiloride treatment. Amiloride significantly increased serum potassium from 4.6 +/- 0.4 to 5.1 +/- 0.4 mM. Four patients failed amiloride therapy with spontaneous nonsustained ventricular tachycardia. The remaining 31 patients were assessed by repeat programmed stimulation. Six patients had complete antiarrhythmic response, and an additional six patients had less than 15 beats of ventricular tachycardia induced. Therefore, amiloride was an efficacious antiarrhythmic treatment in 12 of 35 (34%) patients. Amiloride concentrations were significantly higher (52 +/- 20 ng/ml) in patients that responded than in patients that did not respond (30 +/- 15 ng/ml). The only electrophysiologic measurement that changed significantly was the ventricular functional refractory period (from 269 +/- 24 to 283 +/- 25 msec, p less than 0.05). Amiloride also suppressed frequent, spontaneous ventricular premature beats in eight of 15 patients (53%). No somatic side effects occurred. Two of the five patients discharged on amiloride therapy developed asymptomatic nonsustained ventricular tachycardia, and this prompted a change in antiarrhythmic therapy. Both died suddenly of arrhythmia during substitute empiric antiarrhythmic drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Duff
H J
HJ
Department of Medicine, University of Calgary, Faculty of Medicine, Alberta, Canada.
Mitchell
L B
LB
Kavanagh
K M
KM
Manyari
D E
DE
Gillis
A M
AM
Wyse
D G
DG
D000328:Adult; D000368:Aged; D000584:Amiloride / Q000494:pharmacology / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents; D002304:Cardiac Pacing, Artificial; D004594:Electrophysiology; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013318:Stroke Volume; D013610:Tachycardia / Q000175:diagnosis / Q000188:drug therapy*
D000889:Anti-Arrhythmia Agents; D000584:Amiloride