Influence of ACE Inhibition on Fluid Metabolism in Chronic Heart Failure and Its Pathophysiologic Relevance

BACKGROUND: In congestive heart failure with water retention, subtraction of body fluid by ultrafiltration causes greater diuresis and clinical improvement in patients who are angiotensin-converting enzyme (ACE)-inhibited, suggesting an influence of ACE inhibitors on fluid metabolism. METHODS AND RESULTS: Patients with moderate congestive heart failure were subjected to ultrafiltration (around 2000 mL) and followed up for 3 months. Usual outpatient therapy, consisting of digoxin, furosemide, and ACE inhibitors (18 patients, group A) and of digoxin and furosemide only (18 patients, group B), was continued throughout the trial. Hemodynamics, renal function, body fluid and electrolytes, plasma norepinephrine, renin activity, aldosterone, and plasma volume were monitored. At 30 and 90 days after ultrafiltration, hormones, renal function, functional capacity (based on cardiopulmonary tests), and extravascular lung water (chest radiograph score) were determined. Soon after ultrafiltration, body weight, plasma volume, and diuresis were reduced (hypovolemia) and hormones were raised (reaction to hypovolemia). In the next 4 days, all these variables reverted to the pre-ultrafiltration values in group B; in group A diuresis and plasma volume recovered, body weight was still reduced, and hormones became lower than baseline. These changes persisted in the next 3 months. An early reduction of extravascular lung water continued long term in group A only, associated with increase of exercise tolerance time and oxygen uptake and decrease of the dead space/tidal volume ratio. CONCLUSIONS: In congestive heart failure, ACE inhibition persistently prevented fluid accumulation once the excess of body fluid had been withdrawn with a nonpharmacologic method, resulting in sustained improvement in functional capacity. Reduction in circulating norepinephrine, aldosterone, and renin did not seem to be the cause but the consequence of this action, whose mechanisms remain undefined.