Nesiritide is a rapid vasodilator that mimics the action of an endogenous hormone - human
B-type natriuretic peptide (BNP). BNP is produced naturally in the ventricles of the heart in
response to stretch.
Nesiritide decreases systemic vascular resistance (SVR), pulmonary capillary wedge pressure
(PCWP), right atrial pressure (RAP), and mean pulmonary arterial pressure. Nesiritide does
not affect the heart rate, but does increase the stroke volume and consequently cardiac
output, resulting in a decrease in the symptoms of decompensated heart failure. It is
generally well tolerated, with the major negative side effect being hypotension. When
compared to standard therapy consisting of dobutamine and nitroglycerin, nesiritide had
similar vasodilatory effects, but showed a lower incidence of arrhythmia.
Nesiritide has been approved for IV treatment of patients with acutely decompensated
congestive heart failure. Although studies have tested the effectiveness and safety of
nesiritide in adult CHF patients, this has not been done in children.
Subjects enrolled in this study will be pediatric (<21 years) patients carrying a diagnosis
of dilated cardiomyopathy with decompensated congestive heart failure. The standard of care
for these patients is to undergo cardiac catheterization with placement of a Swan-Ganz
catheter for hemodynamic monitoring. Subjects will be randomly assigned to receive either
Nesiritide or placebo (5% Dextrose). The infusion will then be continued for a total of
twenty-four hours. During this one day period, measurements of systemic blood pressure,
central venous pressure (right atrial pressure), pulmonary capillary wedge pressure, cardiac
output, mixed venous saturation, pulmonary vascular resistance, and systemic vascular
resistance will be measured at regularly scheduled intervals. The Swan-Ganz catheter will
remain in place for 2 hours after the discontinuation of study drug, and then removed.
The objectives of this study are:
1. To assess the efficacy of Nesiritide therapy in decreasing the pulmonary capillary wedge
pressure, right atrial pressure, and systemic vascular resistance in children with
dilated cardiomyopathy.
2. To assess the efficacy of Nesiritide in decreasing pulmonary edema and increasing
cardiac index in the above mentioned population.
3. To assess the safety of both bolus administration and continuous infusion of Nesiritide
in children with dilated cardiomyopathy.
4. To assess the pharmacokinetics of Nesiritide in this population.