Amiloride improves hemodynamics in patients with chronic congestive heart failure treated with chronic digoxin and diuretics

Summary

Potassium-sparing diuretics have been reported to decrease the positive inotropic effect of digoxin. We studied the hemodynamic effects of amiloride in patients taking digoxin for chronic heart failure. Eleven men with a history of congestive heart failure were studied in a double blind, cross-over, placebo controlled trial with the patients on digoxin alternating placebo with amiloride. After 7 days on the trial drug, a Swan-Ganz catheter was placed in the pulmonary artery and measurements made at rest and with increasing degrees of supine bicycle exercise. Right-sided and pulmonary artery wedge pressures and systemic arterial pressures, as well as cardiac outputs, were measured. After a 7 day washout period, placebo (P) and Amiloride (A) were switched and after 7 days on the therapy, a second hemodynamic study at rest and varying degrees of supine bicycle exercise was repeated.

At rest there were no significant differences in the rightsided, pulmonary arterial wedge pressure or cardiac outputs between the patients on Amiloride (A) versus placebo (P). During exercise there were significant differences between (P) and (A) at the 50 watt-second stage of exercise. Right atrial pressures (P = 15.0 ± 6.8 mm Hg vs A = 10.5 ± 5.4 mm Hg), PA wedge pressure (P = 28.6 ± 8.5 vs A = 22.1 ± 7.3 mm Hg), PA diastolic pressure (P = 32.2 ± 9.9 mm Hg) vs A = 21.6 ± 10.0 mm Hg), and mean PA pressure (P = 44.4 ± 11.0 vs A = 38.9 ± 12.5 mm Hg), were all lower on (A) than on (P) and the left ventricular stroke work index (LVSWI) (P = 69.5 ± 18.0 vs A = 77.9 ± 22.2 Gm-m/m²), stroke volume index (P = 44.9 ± 8.8 vs A = 46.2 ± 11.4) cc/beat/m² were higher than on placebo. This study clearly demonstrates no decrease in the inotropic action of digoxin when A was added to a regimen of digoxin and diuretics combined, and may possibly improve ventricular performance compared to digoxin and diuretics alone. The mechanism by which the A improves the ventricular function and promptly increases the inotropic effect in patients taking digoxin is unclear. The addition of (A) to digoxin appears to be safe and may provide clinical benefit above and beyond potassium-sparing.