Key Inclusion Criteria:

1. Hospitalized for acute decompensated heart failure.
2. Systolic blood pressure ≥ 105 mmHg and ≤ 180 mmHg screening
3. Renally compromised.
4. Received or planned to receive IV bolus diuretic at any time before the start of study drug infusion.
5. Female patients must be post-menopausal or surgically sterile.

Key Exclusion Criteria:

1. Acute or suspected acute myocardial infarction (AMI) or troponin levels > 5X the upper limit of normal at the institution's local laboratory
2. Cardiogenic shock
3. Evidence of uncorrected volume or sodium depletion other clinical condition that would predispose the patient to adverse events
4. Clinically significant aortic or mitral valve stenosis
5. Temperature >38°C (oral or equivalent), sepsis or active infection requiring IV anti-microbial treatment
6. ADHF due to significant arrhythmias
7. Severe renal failure defined as creatinine clearance < 30 mL/min
8. Current or planned ultrafiltration, hemofiltration, or dialysis
9. Significant pulmonary disease
10. Major neurologic event, including cerebrovascular events in the prior 60 days.
11. Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy (not including restrictive mitral filling patterns)
12. Known hypersensitivity or allergy to natriuretic peptide or its components, nesiritide, other natriuretic peptides or related compounds