Planned enrollment is approximately twelve subjects with stable chronic heart failure. Enrolled subjects will receive up to eight sequential days of continuous, stepwise, dose increasing, subcutaneous (SQ) infusions of open-label cenderitide via the Insulet Drug Delivery System. Planned infusion rates of cenderitide will be administered to subjects continuously during four, 48-hour infusion periods.

Key Inclusion Criteria:

• Male or female, ≥ 18 years of age
• Body Mass Index (BMI) of 18-40 kg/m2, inclusive
• Current or historical New York Heart Association (NYHA) functional class ≥ II
• At least one of the following: documented systolic heart failure with an ejection fraction (EF) ≤ 40% and/or a historical measurement of plasma BNP ≥ 150 pg/mL (or NT-proBNP ≥ 600 pg/mL)
• Systolic blood pressure 100-160 mmHg
• Stable and compliant treatment with oral heart failure medications for at least 4 weeks prior to Screening

Key Exclusion Criteria:

• Known hypersensitivity or allergy to natriuretic peptide or its components, nesiritide, other natriuretic peptides or related compounds
• Current clinical diagnosis of acute decompensated heart failure (ADHF)
• Clinical diagnosis of acute coronary syndrome (ACS) within 30 days prior to Screening.
• Symptomatic postural hypotension
• Evidence of uncorrected volume or sodium ≤ 130 mmol/L or other condition that would predispose the patient to adverse events
• Clinically significant aortic or mitral valve stenosis
• Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy (not including restrictive mitral filling patterns)
• Severe renal failure defined as creatinine clearance < 45 mL/min as estimated by either the Cockcroft-Gault or the MDRD equations
• Significant pulmonary disease (e.g., history of oral daily steroid dependency, history of Carbon Dioxide (CO2) retention or need for intubation for acute exacerbation, or currently receiving IV steroids)
• Known hepatic impairment as indicated by any of the following: A) total bilirubin > 3 mg/dL; B) albumin < 2.8 mg/dL, with other signs or symptoms of hepatic dysfunction; C) increased ammonia levels, if performed, with other signs or symptoms of hepatic dysfunction