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

Abstract

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 right-sided, 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Relaxation and the Role of Calcium in Isolated Contracting Myocardium From Patients With Hypertensive Heart Disease and Heart Failure With Preserved Ejection Fraction

“…49, 50 In a small patient study, amiloride was reported to improve exercise hemodynamics and LVEDP in heart failure patients. 51 Our results suggest that none of these agents can improve myocardial relaxation in HFpEF or prevent incomplete relaxation at high rates. They also suggest that increased Na + is an unlikely culprit underlying slowed and incomplete relaxation in HHD and HHD+HFpEF, likely because the cellular Na + /K + -ATPase is capable of maintaining normal Na + -levels.…”

The use of diuretics in heart failure with congestion — a position statement from the Heart Failure Association of the European Society of Cardiology

“…Several trials are ongoing in testing the disease‐modifying effect of SGLT2 inhibitors in the setting of both chronic and acute heart failure. Amiloride inhibits distal epithelial sodium channels (ENaC), and anecdotal evidence suggests that ENaC inhibition can result in decongestion with a lowering of filling pressures . Furthermore, chronic over‐expression of ENaC has been implicated in the thiazolidinedione‐mediated volume retention witnessed in diabetics.…”

Inhibitory effects of amiloride on the current mediated by native GABAA receptors in cultured neurons of rat inferior colliculus

“…Amiloride, a potassium‐sparing diuretic, is used clinically for the management of renal failure, 1 hypertension 2 and congestive heart failure 3 and experimentally as a pharmacological agent 4–6 . Amiloride exerts its effects by blocking Na + channels with high affinity 7,8 and H + channels 9 .…”