Aldosterone is a potent mineralocorticoid that promotes electrolyte imbalance in patients with disorders of sodium, potassium, magnesium homeostasis and water retention. This imbalance can cause myocardial changes that may play a role in the development of ventricular arrhythmia, a common cause of sudden death in persons with congestive heart failure (CHF). The inhibition of angiotensin-converting enzyme (ACE) by reducing circulating angiotensin II levels may suppress aldosterone production. However, the level of suppression may be inadequate because the reduction typically is temporary. Ramires and associates evaluated the effect of spironolactone, a synthetic steroid that acts as an aldosterone receptor antagonist, on the incidence of ventricular arrhythmia in patients with CHF.

Thirty-five patients with New York Heart Association class III CHF secondary to dilated or ischemic cardiomyopathy were randomized to receive standard treatment or standard treatment plus spironolactone. All patients had a baseline left ventricular ejection fraction of less than 35 percent. Standard treatment consisted of digoxin, captopril or enalapril, potassium chloride and furosemide at dosages adjusted according to clinical parameters. Patients were followed for 20 weeks, beginning with a four-week observation period between randomization and treatment. The spironolactone dosage started at 50 mg per day for 12 weeks and was then decreased to 25 mg per day for the final four weeks of the study. Metabolic and electrolyte studies were obtained at baseline and at regular intervals throughout the study period. In addition, at baseline and every four weeks, all participants were monitored with 24-hour electrocardiography (Holter monitor).

The frequency of ventricular premature complexes (VPCs) and nonsustained ventricular tachycardia (VT) after exercise decreased significantly in the spironolactone group. Combination treatment with an ACE inhibitor and spironolactone may reduce arrhythmia by decreasing the receptor binding of circulating aldosterone or by improving electrolyte regulation and maintaining more physiologic levels of serum magnesium. A direct positive inotropic effect and an increase in the refractory period also have been postulated as possible antiarrhythmia mechanisms of spironolactone.

The authors conclude that spironolactone reduces the number of VPC and VT episodes in patients with CHF. The exact physiologic cause of this effect and its role in actual improvement in mortality rates require further study.

editor's note: Evidence confirming the utility of spironolactone in patients with cardiac disease is becoming greater. With the recognition of aldosterone as an important factor in the pathophysiology of heart failure, studies have confirmed that the use of low-dose spironolactone in patients with severe CHF and a left ventricular ejection fraction of less than 35 percent can reduce the risk of morbidity and death. The mechanism for this benefit is most likely a blockade of aldosterone receptors. The most common side effect of spironolactone therapy is gynecomastia or breast pain in men. Serious hyperkalemia is rare when doses are kept low.—r.s.