Aldosterone escape during ACE inhibitor therapy in chronic heart failure.
In the setting of chronic heart failure (CHF), therapy with angiotensin converting enzyme (ACE) inhibitors generally reduces serum aldosterone levels acutely. However, long-term ACE inhibition is associated with aldosterone suppression that is weak, variable, and unsustained, i.e. aldosterone 'escape'. Magnesium loss caused by aldosterone and by diuretics can contribute to coronary artery spasm and arrhythmias. Aldosterone can block noradrenaline uptake by the myocardium; extracellular catecholamines may lead to arrhythmias and ischaemia. Aldosterone has been shown to have an acute arrhythmogenic effect as well as a potential detrimental effect on baroreflex function, a marker of prognosis in CHF. Both angiotensin II and aldosterone may stimulate myocardial fibrosis, which is associated with a higher incidence of malignant ventricular arrhythmias. ACE inhibition initiated early in the progression of CHF may prevent development of patchy myocardial fibrosis and its inherent arrhythmias and thus reduce the incidence of sudden death. Spironolactone therapy added to the regimen of an ACE inhibitor and diuretic can induce natriuresis and magnesium retention, increase myocardial noradrenaline uptake, and reduce the incidence of arrhythmias.
Struthers
A D
AD
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, U.K.
D000450:Aldosterone / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000517:prevention & control; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D004719:Endomyocardial Fibrosis / Q000097:blood / Q000517:prevention & control; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008134:Long-Term Care; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D009206:Myocardium / Q000473:pathology; D012307:Risk Factors; D013148:Spironolactone / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone