Neurohormonal activation rapidly decreases after intravenous therapy with diuretics and vasodilators for class IV heart failure.
OBJECTIVE
This study was designed to determine whether therapy with vasodilators and diuretics, designed to normalize loading conditions in decompensated heart failure (HF), reduces neurohormonal activation in the short term. BACKGROUND; Elevated vasoactive neurohormone levels in chronic HF have adverse prognostic impact and may be targeted by specific therapies.


METHODS
Endothelin-1, catecholamines, renin, aldosterone, angiotensin and atrial natriuretic peptides (ANP, N-ANP and BNP) were measured in 34 patients with advanced HF before and after hemodynamically guided therapy with vasodilators and diuretics. The therapy was designed to reduce filling pressures and systemic vascular resistance (SVR) without inotropic therapy. Blood was drawn before therapy (A), after initial diuretic and nitroprusside therapy to optimize hemodynamics (B, mean 1.4 days) and after transition to an oral regimen designed to maintain improved hemodynamics (C, mean 3.4 days).


RESULTS
Mean pulmonary wedge pressure fell from 31 to 18 mm Hg, right atrial pressure from 15 to 8 mm Hg, and SVR from 1,780 to 1,109 dynes/s/cm(-5). Cardiac index increased from 1.7 to 2.6 l/min/m(2) without intravenous inotropic agents (all p < or = 0.05). Average endothelin levels declined by 30%, from 7.7 to 5.5 pg/ml, and remained low at time point C, 5.2 pg/ml (p < 0.01). Norepinephrine was 858 at time A, 817 at time B, and fell by time C to 608 pg/ml (p < or = 0.05). The mean plasma BNP level fell by 26% after only 1.4 days and by 53% at time C (p < 0.001).


CONCLUSIONS
Neurohormonal activation rapidly decreases after short-term therapy tailored to decrease severely elevated filling pressures and SVR without inotropic agents. Therapy designed to address neurohormonal activation should include therapy to improve severe resting hemodynamic compromise.
Johnson
Wendy
W
Brigham and Women's Hospital, Cardiovascular Division, Harvard Medical School, Boston, Massachusetts 02115, USA.
Omland
Torbjørn
T
Hall
Christian
C
Lucas
Caroline
C
Myking
Ole L
OL
Collins
Caroline
C
Pfeffer
Marc
M
Rouleau
Jean-Lucien
JL
Stevenson
Lynne W
LW
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D004232:Diuretics / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood*; D009599:Nitroprusside / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D018377:Neurotransmitter Agents; D014665:Vasodilator Agents; D009599:Nitroprusside