Endogenous B-type natruretic peptide (BNP) concentrations correlate with heart failure (HF) severity and are significantly elevated in severe end-stage HF patients. However, normal biologic compensatory responsiveness to BNP is attenuated in patients with severe HF. Patients who are UNOS 1B cardiac transplant candidates have relatively few options for therapy, despite the fact that they constitute a very ill patient population. These options include getting a transplant, if one is available, receiving intravenous inotropes and/or vasodilators, or being implanted with a circulatory support device (e.g. Left Ventricular Assist Device). Natrecor (Nesiritide) is a human recombinant form of BNP approved for use in the treatment of acute decompensated HF. Limited information is available from controlled clinical trials on the effects of Natreor (nesiritide) infusion for longer than 72 hours. However, based on reports in the literature, Natrecor (nesiritide) has been used by independent investigators for much longer durations in end-stage HF patients, including UNOS Status 1B cardiac transplant candidates, who are refractory to standard care. In these patients, Natrecor (nesiritide) has been safely administered by continuous infusion for more than 2 and up to 210 days. These experiences showed that continuous Natrecor (nesiritide) infusion was well tolerated, uniformly improved hemodynamics (circulation of the blood and the forces involved), maintained stable renal (kidney) function, and reduced the need for ventricular assist devices during the prolonged wait for heart transplant. In controlled clinical trials reported in literature, Natrecor (nesiritide) was given concomitantly with several other standard HF therapeutic agents, such as diuretics, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, dopamine, dobutamine, anticoagulants, digoxin, and oral nitrates. Concomitant dosing was well tolerated, and no drug interactions were observed. No randomized controlled trial has been conducted to evaluate the safety of combination nesiritide and milrinone therapy. Several investigations were undertaken because of concerns over the potential additive hypotensive (lowering blood pressure) effect that these two agents may exert when administered concurrently. The study investigators reported that concurrent dosing of milrinone and nesiritide appeared to be safe and beneficial, without evidence of an additive hypotensive (lowering blood pressure) effect. The TMAC trial will investigate the safety and efficacy of Natrecor (nesiritide), compared with placebo, when added to standard care in the management of end-stage refractory HF.This prospective, randomized(patients are assigned different treatments based on chance), parallel, multicenter, double-blind (neither the doctor nor the patient knows whether the patient is being administered a placebo or the test drug), placebo-controlled study will be conducted with UNOS Status 1B (or equivalent) cardiac transplant candidates who are receiving standard care and continuous IV infusion of dobutamine or milrinone while awaiting heart transplantation. Approximately 120 patients will participate in this study. Enrolled patients will be randomized 1:1 to receive Natrecor (nesiritide) by continuous infusion in addition to standard care and one inotrope (drugs such as dobutamine or milrinone used to increase the heart rate and improve the force of cardiac contraction), or to receive placebo by continuous infusion in addition to standard care and one inotrope (dobutamine or milrinone). Patients will be managed as inpatients or outpatients, according to the guidelines in this protocol and study center practices. All patients will continue to receive their usual long-term cardiac medications (excluding commercial nesiritide). Study drug dose adjustments may be made according to the guidelines in this protocol and the investigator's clinical judgment, and in accordance with the dosing guidelines.Study drug will be administered as a continuous intravenous infusion under the control of a programmable ambulatory infusion pump for the 28-day treatment period. Patients will be hospitalized for study drug initiation and titration to ensure safety, observe tolerability, and achieve the recommended study drug dose. Day 0 (Screening) will entail completing required procedures and randomization. Baseline and screening procedures may occur on the same day. A window of up to 7 days will be permitted between Day 0 (Screening) and Day 1 (Baseline) visits if circumstances delay initiation of study drug dosing. The following day, Day 1 (Baseline), continuous infusion of study drug will begin. Patients will be hospitalized for a minimum of 3 days after starting the study drug for titration and dose optimization. A dose optimization period of up to 5 days will be permitted. Patients will be eligible for discharge following completion of the study procedures on the 4th dosing day (Day 4). Patients will return to the clinic for weekly visits (± 2 days) through Day 28 (Termination of Treatment) and again at Day 35 for a 7-day post dosing safety visit. On the Day 28 visit (Termination of Treatment), Patients may be hospitalized for up to 24 hours at the investigator's discretion to undergo end of treatment study procedures. This study includes two substudies: the Pulmonary Function Testing Substudy and the Glomerular Filtration Rate Substudy. All TMAC Patients will be asked to participate in these substudies. Participation is optional and does not affect enrollment or participation in TMAC. The Study Hypothesis is that continuous administration of Natrecor (nesiritide) over 28 days when added to standard care (including inotropes) is safe and provides a clinical benefit when compared to placebo added to standard care (including inotropes) therapy. Study drug will be administered continuously as a fixed-rate infusion for 28 days without a bolus dose. Natrecor (nesiritide) dosing will begin at 0.005 mcg/kg/min and may be titrated to a maximum dose of 0.015 mcg/kg/min.