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.


OBJECTIVE
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Diuretics were withdrawn in 26 stabilized heart failure patients with systolic dysfunction (ejection fraction [EF]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).


CONCLUSIONS
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.
Galve
Enrique
E
Servei de Cardiologia, Hospital General Universitari Vall d'Hebron, Pg Vall d'Hebron 119-129, 08035 Barcelona, Spain. egalve@vhebron.net
Mallol
Anna
A
Catalan
Robert
R
Palet
Jordi
J
Méndez
Stella
S
Nieto
Elsa
E
Diaz
Anna
A
Soler-Soler
Jordi
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D009320:Atrial Natriuretic Factor / Q000097:blood; D004232:Diuretics / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012083:Renin / Q000097:blood; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013375:Substance Withdrawal Syndrome
D004232:Diuretics; D049994:Sodium Potassium Chloride Symporter Inhibitors; D009320:Atrial Natriuretic Factor; D012083:Renin