CD-NP in Subjects With Stable Chronic Heart Failure

Inclusion Criteria:

1. Male and non-pregnant female subjects, aged 21 or above, with stable chronic HF of primary cardiac etiology, resting left ventricular ejection fraction (LVEF) ≤ 40 % documented within the last 2 years, and New York Heart Association functional class I - III symptoms
2. Be willing to provide informed consent.

Exclusion Criteria:

1. Known allergy or other adverse reactions to exogenous natriuretic peptides (CD-NP or its components, nesiritide, other natriuretic peptides, or related compounds).
2. Women who are pregnant, or breast-feeding.
3. Having received nesiritide for within 7 days prior to prior to entry into the study.
4. Having received any investigational drug or device within 30 days prior to entry into the study.
5. Clinically unstable patients (e.g. systolic blood pressure < 90 mmHg, ongoing requirement for vasopressors or mechanical circulatory support, or mechanical ventilation).
6. Recent hospitalization for decompensated HF or recent defibrillation for cardiac resuscitation within 30 days prior to randomization.
7. Prior organ transplantation, being on a waiting list for organ transplantation, or ongoing requirement for longterm vasoactive support.
8. Patients with guarded prognosis who are unlikely to derive meaningful benefit from CD-NP.
9. Use of sulfonamides, non-steroidal anti-inflammatory drugs, probenecid, or other drugs that are known to alter renal function within 5 half-lives prior to the first dose of CD-NP or placebo.
10. Presence of cardiac lesions or comorbidities that may contraindicate the use of natriuretic peptides, such as clinically significant cardiac valvular stenosis, hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or uncorrected congenital heart disease that contraindicates the use of vasodilators.
11. History of blood pressure > 190/115 mmHg or unexplained syncope within the past 3 months.
12. Symptomatic carotid artery disease, known critical carotid stenosis, or stroke within the past 3 months
13. Clinically significant renal artery stenosis
14. Baseline hemoglobin < 10.0 g/dL.
15. Serum sodium < 130 mEq/L, potassium < 3.6 mEq/L, or magnesium < 1.7 mEq/L.
16. Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at least 5 times the upper limit of normal or bilirubin at least 3 times the upper limit of normal
17. Creatinine clearance (CrCl) < 50 ml.min-1.1.73m-2, as calculated by Cockcroft-Gault formula and adjusted for body surface area within the past year or at screening, or requirement for dialysis.
18. History of alcohol abuse within the past 6 months.
19. Consumption of a phosphodiesterase-5 inhibitor (sildenafil, vardenafil, or tadalafil) within 72 hours of receiving CD-NP or placebo.
20. Inability to communicate effectively with study personnel.
21. bmi>38