EFFECTS OF SPIRONOLACTONE ON EXERCISE CAPACITY AND NEUROHORMONAL FACTORS IN PATIENTS WITH HEART-FAILURE TREATED WITH LOOP DIURETICS AND ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR

1. Treatment with spironolactone is reported to be useful when combine d with loop diuretics and an angiotensin-converting enzyme (ACE) inhib itor in severe congestive heart failure (CHF). However, the effects of the addition of spironolactone on exercise capacity and neurohormonal variables have not been demonstrated. This study determined the effec ts of additive spironolactone on exercise capacity and neurohormonal f actors in patients with mild CHF. 2. Oxygen uptake (VO2), plasma norep inephrine (NE), renin activity (PRA), angiotensin II (AII), aldosteron e (ALD), and atrial natriuretic peptide (ANP) were measured at rest an d after peak exercise in nine patients with CHF (six idiopathic and th ree ischemic cardiomyopathy; New York Heart Association (NYHA) classes II and III) who were already taking furosemide (mean 29+/-5 mg/day) a nd enalapril (mean 4.7+/-0.8 mg/day). Studies were repeated after 16 w eeks of treatment with additive single daily dose of 25 mg of spironol actone. In four of nine patients, the exercise test was repeated after a 4-weeks washout of spironolactone. 3. Treatment with spironolactone caused natriuresis, decreased cardiothoracic ratio in chest X-ray (be fore vs. after treatment: 53.7+/-1.2 vs. 50.7+/-1.4%, P<0.01), and imp roved NYHA functional class. Peak VO2 (17.1+/-1.6 vs. 17.5+/-2.2 ml/mi n/kg, NS) and heart rate and blood pressure responses to exercise were not altered. Resting NE (215+/-41 vs. 492+/-85 pg/ml, P<0.01) and res ting PRA (8.2+/-2.3 vs. 16.2+/-4.1 ng/ml/hr, P<0.01) as well as peak N E (1618+/-313 vs. 2712+/-374 pg/ml, P<0.01) and peak PRA (12.8+/-3.2 v s. 28.1+/-11.8 ng/ml/hr, P=0.17) were augmented after additive spirono lactone. ALD and AII were insignificantly increased, and ANP was insig nificantly decreased at peak exercise after spironolactone treatment. Spironolactone washout was associated with a trend of the neurohormone s to return toward pretreatment values. 4. In conclusion, chronic addi tive treatment with spironolactone was associated with neurohormonal a ctivation both at rest and during exercise without changing the exerci se capacity of patients with mild CHF who were already on loop diureti cs and ACE inhibitor therapy. (C) 1998 Elsevier Science Inc.