Clinical and neurohumoral consequences of diuretic withdrawal in patients with chronic, stabilized heart failure and systolic dysfunction

Background: Loop diuretics are beneficial in heart failure in the short term because they eliminate fluid retention, but in the long-term, they could adversely influence prognosis due to activation of neurohumoral mechanisms. Aims: To explore the changes induced by diuretic withdrawal in chronic nonadvanced heart failure. Methods: Diuretics were withdrawn in 26 stabilized heart failure patients with systolic dysfunction (ejection fraction [EF]< 45%). Clinical status was evaluated by physical exam, exercise capacity (corridor test) and New York Heart Association (NYHA) class. Biochemical and neurohumoral determinations were performed at baseline and at 3 months. Results: At 3 months, 17 out of 26 patients (65%) were able to tolerate diuretic interruption without a deterioration in exercise capacity or New York Heart Association functional class. Renal function parameters improved (baseline urea 46.2 +/- 10.8 to 39.2 +/- 10.1 mg/dl at 3 months, p=0.014; creatinine 1.1 +/- 0.23 to 0.98 +/- 0.2 mg/dl, p=0.013). Glucose metabolism also improved (fasting glucose 151 91 to 122 +/- 14 mg/dl, p=0.035). Heart rate and systolic blood pressure did not significantly change, while diastolic blood pressure increased (from 80 +/- 10 to 87 +/- 13 mm Hg, p=0.006). Neurohumoral determinations showed a decrease in plasma renin activity (4.19 +/- 5.96 to 2.88 +/- 4.98 ng/ml, p=0.026), with no changes in aldosterone, arginine-vasopressin, endothelin-1 and norepinephrine. In contrast, atrial natriuretic peptide significantly increased (115 +/- 87 to 168 +/- 155 pg/ml, p=0.004). Conclusion: Diuretic withdrawal in stabilized heart failure with systolic dysfunction is associated with an improvement in renal function parameters, glucose metabolism and some neurohumoral parameters, such as plasma renin activity; however, atrial natriuretic peptide levels increased. (c) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.