FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

A correction has been published: N Engl J Med 2000;343(20):1504.

Previous Volume 343:246-253 July 27, 2000 Number 4 Next

Abstract PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article Related Article PubMed Citation

ABSTRACT

Background Intravenous infusion of nesiritide, a brain (B-type) natriuretic peptide, has beneficial hemodynamic effects in patients with decompensated congestive heart failure. We investigated the clinical use of nesiritide in such patients.

Methods Patients hospitalized because of symptomatic congestive heart failure were enrolled in either an efficacy trial or a comparative trial. In the efficacy trial, which required the placement of a Swan–Ganz catheter, 127 patients with a pulmonary-capillary wedge pressure of 18 mm Hg or higher and a cardiac index of 2.7 liters per minute per square meter of body-surface area or less were randomly assigned to double-blind treatment with placebo or nesiritide (infused at a rate of 0.015 or 0.030 µg per kilogram of body weight per minute) for six hours. In the comparative trial, which did not require hemodynamic monitoring, 305 patients were randomly assigned to open-label therapy with standard agents or nesiritide for up to seven days.

Results In the efficacy trial, at six hours, nesiritide infusion at rates of 0.015 and 0.030 µg per kilogram per minute decreased pulmonary-capillary wedge pressure by 6.0 and 9.6 mm Hg, respectively (as compared with an increase of 2.0 mm Hg with placebo, P<0.001), resulted in improvements in global clinical status in 60 percent and 67 percent of the patients (as compared with 14 percent of those receiving placebo, P<0.001), reduced dyspnea in 57 percent and 53 percent of the patients (as compared with 12 percent of those receiving placebo, P<0.001), and reduced fatigue in 32 percent and 38 percent of the patients (as compared with 5 percent of those receiving placebo, P<0.001). In the comparative trial, the improvements in global clinical status, dyspnea, and fatigue were sustained with nesiritide therapy for up to seven days and were similar to those observed with standard intravenous therapy for heart failure. The most common side effect was dose-related hypotension, which was usually asymptomatic.

Conclusions In patients hospitalized with decompensated congestive heart failure, nesiritide improves hemodynamic function and clinical status. Intravenous nesiritide is useful for the short-term treatment of decompensated congestive heart failure.

Brain (B-type) natriuretic peptide is synthesized in the ventricular myocardium, where its levels increase in patients with congestive heart failure.³ Systemic infusion of nesiritide, a recombinant human brain natriuretic peptide, in patients with congestive heart failure results in beneficial hemodynamic actions, including arterial and venous dilatation, enhanced sodium excretion, and suppression of the renin–angiotensin–aldosterone and sympathetic nervous systems.^4,5,6,7 To determine the clinical value of nesiritide, we undertook two randomized trials involving a total of 432 patients who were hospitalized because of decompensated congestive heart failure. In one trial (an efficacy trial), we used a double-blind, placebo-controlled design to determine the short-term efficacy of nesiritide with regard to hemodynamic measures and symptoms. In the other trial (a comparative trial), we compared nesiritide with standard intravenous agents, which served as active controls, in terms of clinical efficacy and adverse events.

Methods

Study Population

Between October 1996 and July 1997, 432 patients who required hospitalization and intravenous therapy for decompensated congestive heart failure were recruited at a total of 66 medical centers in the United States (23 centers participated in the efficacy trial and 46 centers in the comparative trial; 3 centers participated in both trials). In both trials, the administration of dobutamine, dopamine, and intravenous vasodilators was discontinued at least 30 minutes before the beginning of the study, and the administration of milrinone was discontinued at least 2 hours before the beginning of the study. Patients were excluded from the comparative trial if they had already received an intravenous vasoactive agent for more than four hours. In both trials, entry criteria required patients to have symptomatic congestive heart failure that, in the opinion of the attending physician, warranted admission to the hospital for therapy with one or more intravenous drugs in addition to diuretics. In the efficacy trial, patients were also required to have a Swan–Ganz pulmonary-artery catheter in place and to meet hemodynamic criteria consisting of a pulmonary-capillary wedge pressure of 18 mm Hg or higher, a cardiac index of 2.7 liters per minute per square meter of body-surface area or less, and a systolic blood pressure of 90 mm Hg or higher. The left ventricular ejection fraction was determined by echocardiography or contrast ventriculography. In the comparative trial, a Swan–Ganz catheter was not required but could be used at the discretion of the attending physician. Patients with recent myocardial infarction or unstable angina (within the preceding 48 hours), clinically important valvular stenosis, hypertrophic or restrictive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or active myocarditis were excluded from both trials.

Study End Points

In the efficacy trial, the prespecified primary end point was the change from base line in the pulmonary-capillary wedge pressure six hours after the start of therapy. Secondary end points were the global clinical status, clinical symptoms, and other hemodynamic measurements. In the comparative trial, the prespecified end points were the global clinical status and clinical symptoms.

Randomization and Study-Drug Administration

In each trial, patients were randomly assigned to a treatment group in blocks of 12 by a randomization center that was independent of both the sponsor and the investigators. Nesiritide (Natrecor, Scios, Sunnyvale, Calif.), supplied as 5 mg of lyophilized powder in a 10-ml glass vial, was reconstituted and further diluted with a solution of 5 percent dextrose in water to the appropriate concentration for each dose group.

In the efficacy trial, the patients were randomly assigned to the three treatment groups in a 1:1:1 ratio. The treatments were as follows: placebo consisting of 5 percent dextrose in water, first given as an intravenous bolus and then as an infusion; nesiritide given as a 0.3-µg intravenous bolus followed by an infusion of 0.015 µg per kilogram of body weight per minute; or nesiritide given as a 0.6-µg intravenous bolus followed by an infusion of 0.030 µg per kilogram per minute. The study drugs (nesiritide and placebo) were prepared in identical infusion bags and were infused in a double-blind manner. Each subject received a continuous intravenous infusion of study drug for at least six hours. After the assessments at six hours, the treatment-group assignment was revealed to the investigator by the randomization center. If symptomatic hypotension occurred or the systolic blood pressure decreased to less than 85 mm Hg, the infusion was stopped and then restarted at half the initial infusion rate once the systolic blood pressure had stabilized at more than 90 mm Hg. The infusion rate could not be increased over the initial rate or after a dose reduction. Intravenous agents other than the study drug were withheld during the six-hour double-blind period. Oral vasoactive medications and intravenous diuretics were withheld for four hours before the measurement of base-line hemodynamic variables, and their administration was not resumed until after the six-hour double-blind period.

In the comparative trial, the patients were randomly assigned to the three treatment groups in a 1:1:1 ratio. The treatments were as follows: "standard therapy," consisting of a single intravenous vasoactive agent routinely used for the short-term management of decompensated congestive heart failure (e.g., dobutamine, milrinone, nitroglycerin, or sodium nitroprusside), according to the judgment of the attending physician; nesiritide given as a 0.3-µg intravenous bolus followed by an infusion of 0.015 µg per kilogram per minute; or nesiritide given as a 0.6-µg intravenous bolus followed by an infusion of 0.030 µg per kilogram per minute. Treatment was given on an open-label basis for standard care but was given in a double-blind manner with respect to the dose of nesiritide. At the discretion of the investigator, the doses of all medications could be increased and a second intravenous vasoactive agent could be added to or substituted for the initial drug. Intravenous diuretics and oral medications could be added at any time. Nesiritide could be discontinued if the patient had symptomatic hypotension or a drop in systolic blood pressure to less than 85 mm Hg, with the option to reinstitute the drug at half the previous infusion rate. Patients randomly assigned to nesiritide could continue to receive nesiritide for up to seven days at the discretion of the investigator.

Assessment of Symptoms

In each trial, global clinical status and specific symptoms of congestive heart failure (dyspnea and fatigue) were assessed at base line and six hours after the treatment with the study drug began. In the efficacy trial, the treatment assignment was revealed after the assessment at six hours. In the comparative trial, the global clinical status and symptoms were also evaluated at 24 hours and at the end of therapy (lasting up to 7 days). Global clinical status was rated independently by both the patient and the investigator on a five-category scale (markedly better, better, no change, worse, or markedly worse) that has been used previously in trials of long-term therapy for congestive heart failure.⁸ Dyspnea and fatigue each were rated jointly by the patient and the investigator on a three-category scale (improved, no change, or worse).

Hemodynamic Assessment in the Efficacy Trial

At base line, repeated measurements of the pulmonary-capillary wedge pressure and of the cardiac index that agreed to within 15 percent were required before administration of the study drug. Pulmonary-capillary wedge pressure, cardiac index, mean right atrial pressure, pulmonary arterial pressures, systolic blood pressure, and heart rate were recorded 1 1/2, 3, 4 1 /2, and 6 hours after the start of study-drug administration. In the efficacy trial, plasma levels of aldosterone (measured by radioimmunoassay) and norepinephrine (measured by radioenzymatic assay) were assessed at base line and at six hours.

Statistical Analysis

Data are presented as means ±SD. In the efficacy trial, the effect of the treatment assignment on hemodynamic variables was analyzed by one-way analysis of variance. In both trials, overall comparisons among the treatment groups were performed with the omnibus F test. Pairwise comparisons were made between each dosage of nesiritide and placebo (in the efficacy trial) or standard therapy (in the comparative trial). Outcomes with respect to global clinical status, symptoms of congestive heart failure, and levels of neurohormones were analyzed by nonparametric methods. All reported P values are two-sided, and P values of less than 0.05 were considered to indicate statistical significance.

Results

Base-Line Characteristics

Base-line demographic and clinical characteristics were similar among the patients in the two trials and were similar among the treatment groups within each trial, with the exception of systolic blood pressure, which was lower in the group assigned to nesiritide at 0.015 µg per kilogram per minute than in the group assigned to nesiritide at 0.030 µg per kilogram per minute or the placebo group (P<0.05) (Table 1). Among the 127 patients enrolled in the efficacy trial, there was marked hemodynamic dysfunction, reflected by a mean pulmonary-capillary wedge pressure of 28 mm Hg, a mean cardiac index of 1.9 liters per minute per square meter, and a mean left ventricular ejection fraction of 0.22. Likewise, plasma levels of norepinephrine and brain natriuretic peptide were markedly elevated among the patients in the efficacy trial.

View this table: [in this window] [in a new window]   Table 1. Characteristics of the Patients at Base Line.

 
Efficacy Trial

Five patients discontinued treatment with the study drug before completing the six-hour study period. The reasons for premature termination were sustained ventricular tachycardia in one patient in the placebo group, worsening congestive heart failure in one patient in the group assigned to nesiritide at 0.015 µg per kilogram per minute, and symptomatic hypotension and nausea, an excessive decrease in pulmonary-capillary wedge pressure, and oliguria in one patient each in the group assigned to nesiritide at 0.030 µg per kilogram per minute. Nesiritide caused dose-dependent decreases in pulmonary-capillary wedge pressure, right atrial pressure, systemic vascular resistance, and systolic blood pressure; a moderate increase in cardiac index; and no substantial change in heart rate (Table 2).

View this table: [in this window] [in a new window]   Table 2. Changes in Base-Line Hemodynamic Values at Six Hours in the Efficacy Trial.

 
Global clinical status as judged by the patient was better or markedly better than at base line in 60 percent and 67 percent of the patients in the groups assigned to nesiritide at 0.015 and 0.030 µg per kilogram per minute, respectively, as compared with 14 percent of the patients assigned to placebo (P<0.001 for both comparisons) (Figure 1). There was no change in global status in 25 percent, 23 percent, and 74 percent of patients in the groups assigned to nesiritide at 0.015 and 0.030 µg per kilogram per minute and in the placebo group, respectively. Likewise, in the physician's judgment, global status was better or markedly better in 55 percent and 77 percent of patients in the groups assigned to nesiritide at 0.015 and 0.030 µg per kilogram per minute, respectively, but in only 5 percent of patients in the placebo group (P<0.001 for both comparisons).

View larger version (13K): [in this window] [in a new window]   Figure 1. Effects of Nesiritide and Placebo or Standard Therapy on Global Clinical Status as Judged by the Patient. Open bars represent patients who received placebo (in the efficacy trial), hatched bars patients who received standard therapy (in the comparative trial), and shaded bars and solid bars patients who received nesiritide at 0.015 and 0.030 µg per kilogram per minute, respectively. Bars above the horizontal line at zero indicate the percentage of patients who had improvement or marked improvement, and bars below the line indicate the percentage of patients who had worsening or marked worsening; patients with no change are not shown. The asterisks indicate P<0.001 for the comparison with placebo.

 
At base line, 93 percent of patients reported dyspnea and 96 percent reported fatigue. Dyspnea was rated as improved in 56 percent and 50 percent of the patients receiving nesiritide at 0.015 and 0.030 µg per kilogram per minute, respectively, but in only 12 percent of those receiving placebo (P<0.001 for both comparisons) (Figure 2). Similarly, fatigue was rated as improved by 32 percent and 38 percent of patients receiving nesiritide at 0.015 and 0.030 µg per kilogram per minute, respectively, but in only 5 percent of those receiving placebo (P<0.001 for both comparisons) (Figure 2).

View larger version (21K): [in this window] [in a new window]   Figure 2. Effect of Nesiritide and Placebo or Standard Therapy on Dyspnea and Fatigue. Open bars represent patients who received placebo (in the efficacy trial), hatched bars patients who received standard therapy (in the comparative trial), and shaded bars and solid bars patients who received nesiritide at 0.015 and 0.030 µg per kilogram per minute, respectively. Bars above the horizontal line at zero indicate the percentage of patients who had improvement, and bars below the line indicate the percentage of patients who had worsening; patients with no change are not shown. The asterisks indicate P<0.001 for the comparison with placebo.

 
Plasma aldosterone levels decreased by 2.5 ng per deciliter (69.4 pmol per liter) and 1.6 ng per deciliter (44.4 pmol per liter), respectively, in the groups assigned to nesiritide at 0.015 and 0.030 µg per kilogram per minute but increased by 0.6 ng per deciliter (16.6 pmol per liter) in the placebo group (P= 0.03). Plasma norepinephrine levels did not change significantly in any group (a decrease of 75 pg per milliliter in the group assigned to nesiritide at 0.015 µg per kilogram per minute, an increase of 8 pg per milliliter in the group assigned to nesiritide at 0.030 µg per kilogram per minute, and an increase of 36 pg per milliliter in the placebo group). The mean urine output over six hours (380 ml in the placebo group) was 560 ml and 659 ml in the groups assigned to nesiritide at 0.015 and 0.030 µg per kilogram per minute, respectively (P=0.004).

Comparative Trial

The duration of therapy was similar among the three treatment groups, with 68 to 73 percent of the patients in each group treated for one or two days, 14 to 21 percent treated for three to five days, and 9 to 14 percent treated for more than five days (P= 0.42). Among the 102 patients assigned to standard therapy, dobutamine was the most common choice of medication (in 57 percent of patients), followed by milrinone (19 percent), nitroglycerin (18 percent), dopamine (6 percent), and amrinone (1 percent). A Swan–Ganz catheter was used in 19 percent of the patients receiving standard therapy and 18 percent of the patients receiving either dose of nesiritide.

In all three groups, the patients' global clinical status was improved at 6 hours, at 24 hours, and at the end of therapy (Figure 1). Likewise, dyspnea and fatigue improved in the three groups at all three time points (Figure 2). There were no significant differences in global status, dyspnea, or fatigue among the three groups at any time. Although the patients in the three groups lost similar amounts of weight during the first two days of treatment (between 0.7 and 1.1 kg), intravenous diuretics were given to fewer patients in the groups assigned to nesiritide at 0.015 and 0.030 µg per kilogram per minute (84 percent and 74 percent of patients, respectively) than in the standard-therapy group (96 percent, P<0.001 for both comparisons).

Adverse Events

In both trials, the most common adverse event in the patients treated with nesiritide was dose-related hypotension, which was usually asymptomatic or mild (Table 3). During the six-hour study period in the efficacy trial, symptomatic hypotension occurred in 2 percent and 5 percent of the patients assigned to nesiritide at 0.015 and 0.030 µg per kilogram per minute, respectively, but in none of the patients in the placebo group. Over the longer time course of the comparative trial, symptomatic hypotension occurred in 4 percent of the standard-therapy group, as compared with 11 percent and 17 percent of the nesiritide groups. Symptomatic hypotension led to discontinuation of nesiritide in 1 patient (receiving 0.030 µg per kilogram per minute) in the efficacy trial and in 15 patients (5 receiving 0.015 µg per kilogram per minute and 10 receiving 0.030 µg per kilogram per minute) in the comparative trial.

View this table: [in this window] [in a new window]   Table 3. Adverse Cardiovascular Events.

 
In the comparative trial, bradycardia tended to be more common in the two nesiritide groups (Table 3). The rates of other adverse events were similar among the treatment groups in both trials. The rate of death from all causes through day 21 was 6 percent overall and was similar in the three treatment groups; none of the deaths were attributed to the study drug by the investigators. Concomitant use of angiotensin-converting–enzyme inhibitors, digoxin, or beta-blockers did not appear to alter the incidence or distribution of adverse effects observed in patients assigned to nesiritide.

Discussion

The infusion of nesiritide in patients admitted to the hospital for treatment of decompensated congestive heart failure resulted in improvements in hemodynamic function and rapid and sustained improvements in clinical status. Two aspects of this study represent a departure from the usual way that vasoactive agents for congestive heart failure are evaluated. First, the effect of therapy on the chief symptoms of decompensated congestive heart failure was measured prospectively. Second, the study population comprised patients admitted specifically for management of decompensated congestive heart failure.

The evaluation of drugs for the management of decompensated congestive heart failure has generally focused on measures of hemodynamic function in patients with a relatively stable clinical course. This approach is based on the reasonable assumption that hemodynamic improvements in such patients will translate into relief of symptoms. However, there are at least theoretical reasons why such an assumption might not apply, and it has been suggested that the evaluation of new drugs for decompensated congestive heart failure should measure their effects on symptoms directly.⁸ Our study demonstrates that nesiritide relieves the symptoms of decompensated congestive heart failure. When compared with standard therapy consisting primarily of dobutamine or milrinone, nesiritide was found to result in similar improvements in global clinical status and in the symptoms of decompensated congestive heart failure. We cannot exclude the possibility of bias on the part of the physicians or patients as a result of knowledge of the changes in hemodynamic function (in the efficacy trial) or the open-label design (in the comparative trial).

The study population was specifically selected to represent patients in whom rapid symptomatic and hemodynamic effects are desired. All the patients had been admitted to a hospital for treatment of decompensated congestive heart failure. All had dyspnea or fatigue, and most had both symptoms. Measurement of hemodynamic variables at base line confirmed that severe hemodynamic compromise was present. In addition, plasma levels of norepinephrine and brain natriuretic peptide, which are indicators of the severity of disease, were markedly elevated.

Nesiritide caused a dose-related decrease in pulmonary-capillary wedge pressure. This effect was associated with a decrease in systemic vascular resistance and an increase in the cardiac index. Since nesiritide exerts no direct, positive inotropic action on the myocardium, the increase in cardiac output presumably reflects a reduction in left ventricular afterload. At six hours, the decrease in systemic vascular resistance was associated with mean decreases in systolic blood pressure of 4 and 9 mm Hg in the patients receiving nesiritide at infusion rates of 0.015 and 0.030 µg per kilogram per minute, respectively. The decrease in blood pressure was not associated with reflex tachycardia or an increase in plasma norepinephrine levels in either of these groups.

In the efficacy trial, diuretic therapy was discontinued four hours before the study and not resumed until after measurements at six hours had been made. It is therefore noteworthy that urine output increased in a dose-dependent manner with the infusion of nesiritide. Likewise, in the comparative trial, in which intravenous diuretics could be used as needed, nesiritide was associated with decreased use of intravenous diuretics. These observations are consistent with the direct renal effects of natriuretic peptides.^4,5,6 In addition, the decrease in aldosterone levels in the nesiritide groups may have contributed to sodium excretion. These observations suggest that nesiritide may be helpful in the clinical management of fluid overload in patients with congestive heart failure.

The most common adverse effect of nesiritide was dose-dependent hypotension, which was usually asymptomatic or associated with only mild symptoms. By design, half the patients assigned to nesiritide initially received the drug at a dose of 0.030 µg per kilogram per minute. In clinical practice, nesiritide would be started at a dose of 0.015 µg per kilogram per minute or less, and increases in the dose would be guided by the blood pressure. Therefore, the incidence of hypotension in this study is probably greater than it would be in clinical practice.

Standard therapy for decompensated congestive heart failure relies on the use of intravenous diuretics, dobutamine, milrinone, nitroglycerin, and sodium nitroprusside.² The use of dobutamine and milrinone can be limited by the dose-dependent effects of these drugs on heart rate and arrhythmias.^9,10 Patients taking nitroglycerin are susceptible to the development of tolerance to the drug.¹¹ Although sodium nitroprusside is a potent vasodilator, its use is often limited by the need for close monitoring and by concern about the toxic effects of cyanide or thiocyanide, which are metabolites of sodium nitroprusside. The salutary clinical and hemodynamic profile of nesiritide and the relative absence of adverse effects associated with it circumvent several of these limitations. We therefore suggest that nesiritide would be a valuable addition to the initial treatment of patients admitted to the hospital for decompensated congestive heart failure.

^* Other members of the Nesiritide Study Group are listed in the Appendix.

Source Information

From Boston University Medical Center, Boston (W.S.C., M.M.G); the University of Southern California School of Medicine, Los Angeles (U.E.); the Clinical Research Department, Scios, Sunnyvale, Calif. (D.P.H.); University of Cincinnati Medical Center, Cincinnati (W.T.A., L.E.W.); the University of Alabama at Birmingham, Birmingham (R.C.B.); Scripps Clinic and Research Foundation, La Jolla, Calif. (A.D.J.); University of Rochester Medical Center, Rochester, N.Y. (C.L.); Jacksonville Heart Center, Jacksonville, Fla. (M.N.); Jacksonville Center for Research, Jacksonville, Fla. (W.H.H.); and Albert Einstein College of Medicine, Bronx, N.Y. (T.H.L.).

Address reprint requests to Dr. Colucci at the Section of Cardiovascular Medicine, Boston University Medical Center, 88 E. Newton St., Boston, MA 02118.

References

1. Braunwald E, Colucci WS, Grossman W. Clinical aspects of heart failure. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. 5th ed. Vol. 1. Philadelphia: W.B. Saunders, 1997:445-70. 
2. Stevenson LW, Colucci WS. Management of patients hospitalized with heart failure. In: Smith TW, ed. Cardiovascular therapeutics. Philadelphia: W.B. Saunders, 1996:199-209.
3. Wei CM, Heublein DM, Perrella MA, et al. Natriuretic peptide system in human heart failure. Circulation 1993;88:1004-1009. [Free Full Text]
4. Holmes SJ, Espiner EA, Richards AM, Yandle TG, Frampton C. Renal, endocrine, and hemodynamic effects of human brain natriuretic peptide in normal man. J Clin Endocrinol Metab 1993;76:91-96. [Abstract]
5. Marcus LS, Hart D, Packer M, et al. Hemodynamic and renal excretory effects of human brain natriuretic peptide infusion in patients with congestive heart failure: a double-blind, placebo-controlled, randomized crossover trial. Circulation 1996;94:3184-3189. [Free Full Text]
6. Abraham WT, Lowes BD, Ferguson DA, et al. Systemic hemodynamic, neurohormonal, and renal effects of a steady-state infusion of human brain natriuretic peptide in patients with hemodynamically decompensated heart failure. J Card Fail 1998;4:37-44. [Medline]
7. Mills RM, LeJemtel TH, Horton DP, et al. Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. J Am Coll Cardiol 1999;34:155-162. [Free Full Text]
8. Colucci WS, Packer M, Bristow MR, et al. Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. Circulation 1996;94:2800-2806. [Free Full Text]
9. Tisdale JE, Patel R, Webb CR, Borzak S, Zarowitz BJ. Electrophysiologic and proarrhythmic effects of intravenous inotropic agents. Prog Cardiovasc Dis 1995;38:167-180. [CrossRef][Medline]
10. Anderson JL, Askins JC, Gilbert EM, Menlove RL, Lutz JR. Occurrence of ventricular arrhythmias in patients receiving acute and chronic infusions of milrinone. Am Heart J 1986;111:466-474. [CrossRef][Medline]
11. Packer M, Lee WH, Kessler PD, Gottlieb SS, Medina N, Yushak M. Prevention and reversal of nitrate tolerance in patients with congestive heart failure. N Engl J Med 1987;317:799-804. [Abstract]

The other members of the Nesiritide Study Group were as follows: Efficacy trial — R. Bies, D. Ferguson, and L. Woodworth (University of Colorado Health Sciences Center, Denver Veterans Affairs Medical Center, and Denver Health Medical Center, Denver); R. Bijou (Montefiore Medical Center, Bronx, N.Y.); R. Benza, M. Smith, and A. Trimble (University of Alabama at Birmingham, Birmingham); K. Chatterjee, T. DeMarco, and D. Lau (University of California, San Francisco, San Francisco); G. Dennish III, C. Harrington, and S. Larsen (Scripps Memorial Hospital and San Diego Cardiovascular Associates, San Diego, Calif.); T. Donohue and B. Merkle (St. Louis University Medical Center, St. Louis); M. Slawsky, D. Gauthier, and L. Keane (Boston Medical Center and Boston Veterans Affairs Medical Center, Boston); J.M. Hare and M. Talbot (Johns Hopkins Hospital, Baltimore); R. Hershberger and T. Walker (Oregon Health Sciences Center, Portland); W.B. Hood, Jr., and J. Armstrong (University of Rochester Medical Center–Strong Memorial Hospital, Rochester, N.Y.); M. Ellis (Green Hospital of Scripps Clinic, La Jolla, Calif.); W. Kao and J. O'Sullivan (Rush–Presbyterian–St. Luke's Medical Center, Chicago); M. Kukin, C. Bucholz, and O. O'Campo (Mount Sinai Medical Center, New York); R. Lang and C. Griffis (University of Chicago Hospital, Chicago); M. Galvao (Jack D. Weiler Hospital of Albert Einstein College of Medicine, Bronx, N.Y.); C. Lui and R. Alves (University of Arizona, Tucson); C. Pepine and D. Leach (Shands Medical Center, University of Florida, Gainesville); J. Plehn and C. Carlson (Dartmouth–Hitchcock Medical Center, Lebanon, N.H.); K. Roush and H. Cole (Toledo Hospital, Toledo, Ohio); V.N. Udhoji and J. Dorman (West Los Angeles Veterans Affairs Medical Center, Los Angeles); P.J. Varghese and A. Nys (George Washington University Medical Center, Washington, D.C.); H.O. Ventura, M.R. Mehra, and B. Robichaux (Ochsner Clinic, New Orleans); and B. Gervers (University of Cincinnati Medical Center, Cincinnati). Comparative trial — M. Arendt and E. Springer (Madigan Army Medical Center, Tacoma, Wash.); D.E. Bolster and K. Price (Columbia–Summerville Medical Center, Summerville, S.C.); A. Trimble (University of Alabama at Birmingham, Birmingham); M. Bowles and P. Patterson-Midgley (Columbia Wesley Medical Center, Wichita, Kans.); A. Burger and M. Burger (Beth Israel Deaconess Medical Center, Boston); J. Carley and D. Tracy (Memorial Hospital, Ormond Beach, Fla.); P. Carson and D. Lee (Veterans Affairs Medical Center, Washington, D.C.); P.S. Coleman and S. Campbell (Santa Rosa Memorial, Santa Rosa, Calif.); L. Czer and L. Defensor (Cedars–Sinai Medical Center, Los Angeles); S. El Hafi and R. Keister (Spring Branch Medical Center, Houston); M. El Shahawy and B. Collentine-Smith (Doctors Hospital of Sarasota, Sarasota, Fla.); J. Johnson and P. Tummala (Los Angeles County–University of Southern California Medical Center, Los Angeles); M. Ellestad and F. Swiger (Long Beach Memorial Medical Center, Long Beach, Calif.); R.D. Ensley and M. Thompson (Saint Francis Hospital, Tulsa, Okla.); R. Feldman and T. Saine (Munroe Regional Medical Center, Ocala, Fla.); D. Fishbein and R. Letterer (University of Washington Medical Center, Seattle); L. Ford and J.M. Birt (Roudebush Veterans Affairs Medical Center, Indianapolis); W. Gandy and J. Miller (St. Joseph's Hospital of Atlanta, Atlanta); J. Ghali and L. Sims (Louisiana State University Medical Center, Shreveport); E.M. Gilbert and K. Volkmann (University of Utah Health Sciences Center, Salt Lake City); M. Greenspan and K. Morgan (Grand View Hospital, Sellersville, Pa.); E. Harlamert and L. Tully (Community Hospital East, Indianapolis); C. Buda (Columbia Memorial Hospital, Jacksonville, Fla.); P. Hoagland and S. Harte (Sharp Memorial Hospital and Sharp Cabrillo Hospital, San Diego, Calif.); K. Cease (Green Hospital of Scripps Clinic, La Jolla, Calif.); R. Karlsberg and T. Gerez (Brotman Medical Center and Midway Hospital Medical Center, Beverly Hills, Calif.); S.N. Lanza and P. Walker (Florida Hospital, Orlando); M. Galvao and J. Varela (Jack D. Weiler Hospital of Albert Einstein College of Medicine, Bronx, N.Y.); T.B. Levine and J. Bolenbaugh (Henry Ford Hospital, Detroit); W. Lewis and B. Pierce (University of California, Davis, Medical Center, Sacramento); C. Edgett (University of Rochester Medical Center, Rochester, N.Y.); S. Mallon and S. Gerity (Jackson Memorial Medical Center, University of Miami, Miami); P. McLaughlin and B. Lee (University Hospital, Columbia, Mo.); D. Hartley and K. Miller (Baptist Medical Center and Baptist Medical Center–Beaches, Jacksonville, Fla.); R. Oren and L. Panther (University of Iowa Hospitals and Clinics, Iowa City); S. Promisloff and D. Jones (Tuality Community Hospital, Hillsboro, Oreg.); D.R. Schwartz and D. Marshall (Columbia Regional Medical Center and Lee Memorial Health System, Fort Myers, Fla.); M.A. Silver and U. Bindingnavle (Christ Hospital and Medical Center, Oak Lawn, Ill.); A. Tenaglia and M. Cash (Tulane University Hospital and Clinics and New Orleans Veterans Affairs Medical Center, New Orleans); G. Torre-Amione and J. Higganbotham (Methodist Hospital, Baylor College of Medicine, Houston); K. Vaska and C. Ageton (Sioux Valley Hospital, Sioux Falls, S.D.); R.C. Johnson (Sioux Falls Veterans Affairs Medical Center, Sioux Falls, S.D.); J. Everett (Christ Hospital, Cincinnati); M.N. Walsh and S. Miller (St. Vincent Hospital and Health Care Center, Indianapolis); D. Wilson and D. DeVore (University of Kansas Medical Center, Kansas City); and J.R. Wilson and A. Delmotte (Vanderbilt University Medical Center, Nashville).

Abstract PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article Related Article PubMed Citation

This article has been cited by other articles:

• Tsukamoto, O., Fujita, M., Kato, M., Yamazaki, S., Asano, Y., Ogai, A., Okazaki, H., Asai, M., Nagamachi, Y., Maeda, N., Shintani, Y., Minamino, T., Asakura, M., Kishimoto, I., Funahashi, T., Tomoike, H., Kitakaze, M. (2009). Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure.. J Am Coll Cardiol 53: 2070-2077 [Abstract] [Full Text]  
• Boerrigter, G., Costello-Boerrigter, L. C., Harty, G. J., Huntley, B. K., Cataliotti, A., Lapp, H., Burnett, J. C. Jr. (2009). B-type natriuretic peptide 8-32, which is produced from mature BNP 1-32 by the metalloprotease meprin A, has reduced bioactivity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296: R1744-R1750 [Abstract] [Full Text]  
• Hunt, S. A., Abraham, W. T., Chin, M. H., Feldman, A. M., Francis, G. S., Ganiats, T. G., Jessup, M., Konstam, M. A., Mancini, D. M., Michl, K., Oates, J. A., Rahko, P. S., Silver, M. A., Stevenson, L. W., Yancy, C. W. (2009). 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. J Am Coll Cardiol 53: e1-e90 [Full Text]  
• Jessup, M., Abraham, W. T., Casey, D. E., Feldman, A. M., Francis, G. S., Ganiats, T. G., Konstam, M. A., Mancini, D. M., Rahko, P. S., Silver, M. A., Stevenson, L. W., Yancy, C. W. (2009). 2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. J Am Coll Cardiol 53: 1343-1382 [Full Text]  
• 2009 WRITING GROUP TO REVIEW NEW EVIDENCE AND UPDA, , Jessup, M., Abraham, W. T., Casey, D. E., Feldman, A. M., Francis, G. S., Ganiats, T. G., Konstam, M. A., Mancini, D. M., Rahko, P. S., Silver, M. A., Stevenson, L. W., Yancy, C. W. (2009). 2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation. Circulation 119: 1977-2016 [Full Text]  
• 2005 WRITING COMMITTEE MEMBERS, , Hunt, S. A., Abraham, W. T., Chin, M. H., Feldman, A. M., Francis, G. S., Ganiats, T. G., Jessup, M., Konstam, M. A., Mancini, D. M., Michl, K., Oates, J. A., Rahko, P. S., Silver, M. A., Stevenson, L. W., Yancy, C. W. (2009). 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation. Circulation 119: e391-e479 [Full Text]  
• Elkayam, U., Akhter, M. W., Liu, M., Hatamizadeh, P., Barakat, M. N. (2008). Assessment of renal hemodynamic effects of nesiritide in patients with heart failure using intravascular Doppler and quantitative angiography.. J Am Coll Cardiol Img 1: 765-771 [Abstract] [Full Text]  
• Niederkofler, E. E., Kiernan, U. A., O'Rear, J., Menon, S., Saghir, S., Protter, A. A., Nelson, R. W., Schellenberger, U. (2008). Detection of Endogenous B-Type Natriuretic Peptide at Very Low Concentrations in Patients With Heart Failure. Circ Heart Fail 1: 258-264 [Abstract] [Full Text]  
• Cataliotti, A., Chen, H. H., Schirger, J. A., Martin, F. L., Boerrigter, G., Costello-Boerrigter, L. C., James, K. D., Polowy, K., Miller, M. A., Malkar, N. B., Bailey, K. R., Burnett, J. C. Jr (2008). Chronic Actions of a Novel Oral B-Type Natriuretic Peptide Conjugate in Normal Dogs and Acute Actions in Angiotensin II-Mediated Hypertension. Circulation 118: 1729-1736 [Abstract] [Full Text]  
• Ryan, A., Rosen, D. A., Tobias, J. D. (2008). Preliminary Experience With Nesiritide in Pediatric Patients Less Than 12 Months of Age. J Intensive Care Med 23: 321-328 [Abstract]  
• Oshima, Y., Ouchi, N., Sato, K., Izumiya, Y., Pimentel, D. R., Walsh, K. (2008). Follistatin-Like 1 Is an Akt-Regulated Cardioprotective Factor That Is Secreted by the Heart. Circulation 117: 3099-3108 [Abstract] [Full Text]  
• Burnett, J. C. Jr, Korinek, J. (2008). The Tumultuous Journey of Nesiritide: Past, Present, and Future. Circ Heart Fail 1: 6-8 [Full Text]  
• Hillock, R J, Frampton, C M, Yandle, T G, Troughton, R W, Lainchbury, J G, Richards, A M (2008). B-type natriuretic peptide infusions in acute myocardial infarction. Heart 94: 617-622 [Abstract] [Full Text]  
• Tanaka, T., Tsutamoto, T., Sakai, H., Nishiyama, K., Fujii, M., Yamamoto, T., Horie, M. (2008). Effect of atrial natriuretic peptide on adiponectin in patients with heart failure. Eur J Heart Fail 10: 360-366 [Abstract] [Full Text]  
• Park, K., Itoh, H., Yamahara, K., Sone, M., Miyashita, K., Oyamada, N., Sawada, N., Taura, D., Inuzuka, M., Sonoyama, T., Tsujimoto, H., Fukunaga, Y., Tamura, N., Nakao, K. (2008). Therapeutic Potential of Atrial Natriuretic Peptide Administration on Peripheral Arterial Diseases. Endocrinology 149: 483-491 [Abstract] [Full Text]  
• De Luca, L., Mebazaa, A., Filippatos, G., Parissis, J. T., Bohm, M., Voors, A. A., Nieminen, M., Zannad, F., Rhodes, A., El-Banayosy, A., Dickstein, K., Gheorghiade, M. (2008). Overview of emerging pharmacologic agents for acute heart failure syndromes. Eur J Heart Fail 10: 201-213 [Abstract] [Full Text]  
• Rose, R. A., Giles, W. R. (2008). Natriuretic peptide C receptor signalling in the heart and vasculature. J. Physiol. 586: 353-366 [Abstract] [Full Text]  
• Iglesias, J. I., DePalma, L., Hom, D., Antoniotti, M., Ayoub, S., Levine, J. S. (2008). Predictors of mortality in adult patients with congestive heart failure receiving nesiritide Retrospective analysis showing a potential adverse interaction between neseritide and acute renal dysfunction. Nephrol Dial Transplant 23: 144-153 [Abstract] [Full Text]  
• Mainwaring, R. D., Parise, C., Wright, S. B., Juris, A. L., Achtel, R. A., Fallah, H. (2007). Brain Natriuretic Peptide Levels Before and After Ventricular Septal Defect Repair. Ann. Thorac. Surg. 84: 2066-2069 [Abstract] [Full Text]  
• Green, A. K., Stratton, R. C., Squires, P. E., Simpson, A. W. M. (2007). Atrial Natriuretic Peptide Attenuates Elevations in Ca2+ and Protects Hepatocytes by Stimulating Net Plasma Membrane Ca2+ Efflux. J. Biol. Chem. 282: 34542-34554 [Abstract] [Full Text]  
• McMurray, J. J. V., Teerlink, J. R., Cotter, G., Bourge, R. C., Cleland, J. G. F., Jondeau, G., Krum, H., Metra, M., O'Connor, C. M., Parker, J. D., Torre-Amione, G., van Veldhuisen, D. J., Lewsey, J., Frey, A., Rainisio, M., Kobrin, I., for the VERITAS Investigators, (2007). Effects of Tezosentan on Symptoms and Clinical Outcomes in Patients With Acute Heart Failure: The VERITAS Randomized Controlled Trials. JAMA 298: 2009-2019 [Abstract] [Full Text]  
• Arora, S., Clarke, K., Srinivasan, V., Gradman, A. (2007). Effect of nesiritide on renal function in patients admitted for decompensated heart failure. QJM 100: 699-706 [Abstract] [Full Text]  
• Pankow, K., Wang, Y., Gembardt, F., Krause, E., Sun, X., Krause, G., Schultheiss, H.-P., Siems, W.-E., Walther, T. (2007). Successive Action of Meprin A and Neprilysin Catabolizes B-Type Natriuretic Peptide. Circ. Res. 101: 875-882 [Abstract] [Full Text]  
• Tsutamoto, T., Asai, S., Tanaka, T., Sakai, H., Nishiyama, K., Fujii, M., Yamamoto, T., Ohnishi, M., Wada, A., Saito, Y., Horie, M. (2007). Plasma level of cardiotrophin-1 as a prognostic predictor in patients with chronic heart failure. Eur J Heart Fail 9: 1032-1037 [Abstract] [Full Text]  
• Schwarz, E. R., Najam, S., Akel, R., Sulimanjee, N., Bionat, S., Rosanio, S. (2007). Intermittent Outpatient Nesiritide Infusion Reduces Hospital Admissions in Patients With Advanced Heart Failure. J CARDIOVASC PHARMACOL THER 12: 232-236 [Abstract]  
• Dunn, A., Sachak, S. (2007). Nesiritide and renal function after cardiac surgery. Am J Health Syst Pharm 64: 1582-1584 [Full Text]  
• Heublein, D. M., Huntley, B. K., Boerrigter, G., Cataliotti, A., Sandberg, S. M., Redfield, M. M., Burnett, J. C. Jr (2007). Immunoreactivity and Guanosine 3',5'-Cyclic Monophosphate Activating Actions of Various Molecular Forms of Human B-Type Natriuretic Peptide. Hypertension 49: 1114-1119 [Abstract] [Full Text]  
• Vats, V., DiDomenico, R. J, Wojtynek, J. E, Theobald, J. C, Schumock, G. T (2007). Hospital Policies for Treatment of Acute Decompensated Heart Failure. The Annals of Pharmacotherapy 41: 562-567 [Abstract] [Full Text]  
• Chow, S. L, Peng, J. T, Okamoto, M. P, Heywood, J T. (2007). Effect of Nesiritide Infusion Duration on Renal Function in Acutely Decompensated Heart Failure Patients. The Annals of Pharmacotherapy 41: 556-561 [Abstract] [Full Text]  
• Wu, A. H (2007). Management of patients with non-ischaemic cardiomyopathy. Heart 93: 403-408 [Full Text]  
• Belenkie, I. (2007). Nesiritide Administration in Patients With Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Surgery. J Am Coll Cardiol 49: 727-728 [Full Text]  
• Mentzer, R. M. Jr, Oz, M. C., Sladen, R. N., Graeve, A. H., Hebeler, R. F. Jr, Luber, J. M. Jr, Smedira, N. G., on behalf of the NAPA Investigators, (2007). Effects of Perioperative Nesiritide in Patients With Left Ventricular Dysfunction Undergoing Cardiac Surgery: The NAPA Trial. J Am Coll Cardiol 49: 716-726 [Abstract] [Full Text]  
• Lewis, G. D., Lachmann, J., Camuso, J., Lepore, J. J., Shin, J., Martinovic, M. E., Systrom, D. M., Bloch, K. D., Semigran, M. J. (2007). Sildenafil Improves Exercise Hemodynamics and Oxygen Uptake in Patients With Systolic Heart Failure. Circulation 115: 59-66 [Abstract] [Full Text]  
• deGoma, E. M., Vagelos, R. H., Fowler, M. B., Ashley, E. A. (2006). Emerging Therapies for the Management of Decompensated Heart Failure: From Bench to Bedside. J Am Coll Cardiol 48: 2397-2409 [Abstract] [Full Text]  
• Schwarz, E. R., Jammula, P., Gupta, R., Rosanio, S. (2006). A Case and Review of Acromegaly-Induced Cardiomyopathy and the Relationship Between Growth Hormone and Heart Failure: Cause or Cure or Neither or Both?. J CARDIOVASC PHARMACOL THER 11: 232-244 [Abstract]  
• Iglesias, J., Hom, D., Antoniotti, M., Ayoub, S., Levine, J. S. (2006). Predictors of worsening renal function in adult patients with congestive heart failure receiving recombinant human B-type brain natriuretic peptide (nesiritide). Nephrol Dial Transplant 21: 3458-3465 [Abstract] [Full Text]  
• Mitrovic, V., Seferovic, P. M., Simeunovic, D., Ristic, A. D., Miric, M., Moiseyev, V. S., Kobalava, Z., Nitsche, K., Forssmann, W.-G., Luss, H., Meyer, M. (2006). Haemodynamic and clinical effects of ularitide in decompensated heart failure. Eur Heart J 27: 2823-2832 [Abstract] [Full Text]  
• Chen, H. H., Schirger, J. A., Cataliotti, A., Burnett, J. C. Jr. (2006). Intact acute cardiorenal and humoral responsiveness following chronic subcutaneous administration of the cardiac peptide BNP in experimental heart failure. Eur J Heart Fail 8: 681-686 [Abstract] [Full Text]  
• Hauptman, P. J., Schnitzler, M. A., Swindle, J., Burroughs, T. E. (2006). Use of nesiritide before and after publications suggesting drug-related risks in patients with acute decompensated heart failure.. JAMA 296: 1877-1884 [Abstract] [Full Text]  
• Aaronson, K. D., Sackner-Bernstein, J. (2006). Risk of death associated with nesiritide in patients with acutely decompensated heart failure.. JAMA 296: 1465-1466 [Full Text]  
• Gheorghiade, M., Sopko, G., De Luca, L., Velazquez, E. J., Parker, J. D., Binkley, P. F., Sadowski, Z., Golba, K. S., Prior, D. L., Rouleau, J. L., Bonow, R. O. (2006). Navigating the Crossroads of Coronary Artery Disease and Heart Failure. Circulation 114: 1202-1213 [Full Text]  
• Arora, R. R. (2006). Nesiritide: trials and tribulations.. J CARDIOVASC PHARMACOL THER 11: 165-169 [Abstract]  
• Chen, H. H., Burnett, J. C. Jr (2006). Clinical application of the natriuretic peptides in heart failure. Eur Heart J Suppl 8: E18-E25 [Abstract] [Full Text]  
• London, B. (2006). Natriuretic Peptides and Cardiac Hypertrophy. J Am Coll Cardiol 48: 506-507 [Full Text]  
• Akerman, M. J., Yaegashi, M., Khiangte, Z., Murugan, A. T., Abe, O., Marmur, J. D. (2006). Bronchodilator effect of infused B-type natriuretic Peptide in asthma.. Chest 130: 66-72 [Abstract] [Full Text]  
• Riter, H. G., Redfield, M. M., Burnett, J. C., Chen, H. H. (2006). Nonhypotensive Low-Dose Nesiritide Has Differential Renal Effects Compared With Standard-Dose Nesiritide in Patients With Acute Decompensated Heart Failure and Renal Dysfunction. J Am Coll Cardiol 47: 2334-2335 [Full Text]  
• Prasad, S K, Dargie, H J, Smith, G C, Barlow, M M, Grothues, F, Groenning, B A, Cleland, J G F, Pennell, D J (2006). Comparison of the dual receptor endothelin antagonist enrasentan with enalapril in asymptomatic left ventricular systolic dysfunction: a cardiovascular magnetic resonance study. Heart 92: 798-803 [Abstract] [Full Text]  
• Fontana, D. (2006). Nesiritide: The Latest Drug for Treating Heart Failure. Crit Care Nurse 26: 39-47 [Full Text]  
• Klinger, J. R., Thaker, S., Houtchens, J., Preston, I. R., Hill, N. S., Farber, H. W. (2006). Pulmonary hemodynamic responses to brain natriuretic Peptide and sildenafil in patients with pulmonary arterial hypertension.. Chest 129: 417-425 [Abstract] [Full Text]  
• Nishikimi, T., Maeda, N., Matsuoka, H. (2006). The role of natriuretic peptides in cardioprotection. Cardiovasc Res 69: 318-328 [Abstract] [Full Text]  
• Yancy, C. W., Lopatin, M., Stevenson, L. W., De Marco, T., Fonarow, G. C., for the ADHERE Scientific Advisory Committee and I, (2006). Clinical Presentation, Management, and In-Hospital Outcomes of Patients Admitted With Acute Decompensated Heart Failure With Preserved Systolic Function: A Report From the Acute Decompensated Heart Failure National Registry (ADHERE) Database. J Am Coll Cardiol 47: 76-84 [Abstract] [Full Text]  
• Bauer, J. B., Randazzo, M. A. (2005). Nesiritide for outpatient treatment of heart failure. Am J Health Syst Pharm 62: 2639-2642 [Full Text]  
• Hawkridge, A. M., Heublein, D. M., Bergen, H. R. III, Cataliotti, A., Burnett, J. C. Jr., Muddiman, D. C. (2005). Quantitative mass spectral evidence for the absence of circulating brain natriuretic peptide (BNP-32) in severe human heart failure. Proc. Natl. Acad. Sci. USA 102: 17442-17447 [Abstract] [Full Text]  
• Lafontan, M., Moro, C., Sengenes, C., Galitzky, J., Crampes, F., Berlan, M. (2005). An Unsuspected Metabolic Role for Atrial Natriuretic Peptides: The Control of Lipolysis, Lipid Mobilization, and Systemic Nonesterified Fatty Acids Levels in Humans. Arterioscler. Thromb. Vasc. Bio. 25: 2032-2042 [Abstract] [Full Text]  
• Onat, D., Stathopoulos, J., Rose, A., Newman, K., Sciacca, R. R, Jorde, U. P, Colombo, P. C (2005). Reliability of Nesiritide Infusion via Non-Primed Tubing and Heparin-Coated Catheters. The Annals of Pharmacotherapy 39: 1617-1619 [Abstract] [Full Text]  
• Schuller Gortney, J., Porter, K. B. (2005). Risk of Death With Nesiritide. JAMA 294: 897-898 [Full Text]  
• Cataliotti, A., Schirger, J. A., Martin, F. L., Chen, H. H., McKie, P. M., Boerrigter, G., Costello-Boerrigter, L. C., Harty, G., Heublein, D. M., Sandberg, S. M., James, K. D., Miller, M. A., Malkar, N. B., Polowy, K., Burnett, J. C. Jr (2005). Oral Human Brain Natriuretic Peptide Activates Cyclic Guanosine 3',5'-Monophosphate and Decreases Mean Arterial Pressure. Circulation 112: 836-840 [Abstract] [Full Text]  
• McKie, P. M., Burnett, J. C. Jr (2005). B-Type Natriuretic Peptide as a Biomarker Beyond Heart Failure: Speculations and Opportunities. Mayo Clin Proc. 80: 1029-1036 [Abstract]  
• Nakanishi, M., Saito, Y., Kishimoto, I., Harada, M., Kuwahara, K., Takahashi, N., Kawakami, R., Nakagawa, Y., Tanimoto, K., Yasuno, S., Usami, S., Li, Y., Adachi, Y., Fukamizu, A., Garbers, D. L., Nakao, K. (2005). Role of Natriuretic Peptide Receptor Guanylyl Cyclase-A in Myocardial Infarction Evaluated Using Genetically Engineered Mice. Hypertension 46: 441-447 [Abstract] [Full Text]  
• Abraham, W. T., Adams, K. F., Fonarow, G. C., Costanzo, M. R., Berkowitz, R. L., LeJemtel, T. H., Cheng, M. L., Wynne, J., the ADHERE Scientific Advisory Committee Investiga, , and the ADHERE Study Group, (2005). In-Hospital Mortality in Patients With Acute Decompensated Heart Failure Requiring Intravenous Vasoactive Medications: An Analysis From the Acute Decompensated Heart Failure National Registry (ADHERE). J Am Coll Cardiol 46: 57-64 [Abstract] [Full Text]  
• Rudiger, A., Harjola, V.-P., Muller, A., Mattila, E., Saila, P., Nieminen, M., Follath, F. (2005). Acute heart failure: Clinical presentation, one-year mortality and prognostic factors. Eur J Heart Fail 7: 662-670 [Abstract] [Full Text]  
• Chen, H. H., Cataliotti, A., Schirger, J. A., Martin, F. L., Burnett, J. C. Jr. (2005). Equimolar doses of atrial and brain natriuretic peptides and urodilatin have differential renal actions in overt experimental heart failure. Am. J. Physiol. Regul. Integr. Comp. Physiol. 288: R1093-R1097 [Abstract] [Full Text]  
• Sackner-Bernstein, J. D., Kowalski, M., Fox, M., Aaronson, K. (2005). Short-term Risk of Death After Treatment With Nesiritide for Decompensated Heart Failure: A Pooled Analysis of Randomized Controlled Trials. JAMA 293: 1900-1905 [Abstract] [Full Text]  
• Elkayam, U., Wang, D. J., Dowling, T. C., Meadows, D., Ayala, T., Marshall, J., Minshall, S., Greenberg, N., Thattassery, E., Fisher, M. L., Rao, K., Gottlieb, S. S. (2005). Letter Regarding Article by Wang et al, "Nesiritide Does Not Improve Renal Function in Patients With Chronic Heart Failure and Worsening Serum Creatinine" * Response. Circulation 111: e182-e183 [Full Text]  
• Gheorghiade, M., Zannad, F. (2005). Modern management of acute heart failure syndromes. Eur Heart J Suppl 7: B3-B7 [Abstract] [Full Text]  
• Nieminen, M. S. (2005). Pharmacological options for acute heart failure syndromes: current treatments and unmet needs. Eur Heart J Suppl 7: B20-B24 [Abstract] [Full Text]  
• Burnett, J. C. (2005). Nesiritide: new hope for acute heart failure syndromes?. Eur Heart J Suppl 7: B25-B30 [Abstract] [Full Text]  
• Sackner-Bernstein, J. D., Skopicki, H. A., Aaronson, K. D. (2005). Risk of Worsening Renal Function With Nesiritide in Patients With Acutely Decompensated Heart Failure. Circulation 111: 1487-1491 [Abstract] [Full Text]  
• Kong, S. W., Bodyak, N., Yue, P., Liu, Z., Brown, J., Izumo, S., Kang, P. M. (2005). Genetic expression profiles during physiological and pathological cardiac hypertrophy and heart failure in rats. Physiol. Genomics 21: 34-42 [Abstract] [Full Text]  
• O'Dell, K. M., Kalus, J. S., Kucukarslan, S., Czerska, B. (2005). Nesiritide for secondary pulmonary hypertension in patients with end-stage heart failure. Am J Health Syst Pharm 62: 606-609 [Abstract] [Full Text]  
• Miller, W. L., Hartman, K. A., Burritt, M. F., Borgeson, D. D., Burnett, J. C. Jr, Jaffe, A. S. (2005). Biomarker Responses during and after Treatment with Nesiritide Infusion in Patients with Decompensated Chronic Heart Failure. Clin. Chem. 51: 569-577 [Abstract] [Full Text]  
• Endorsed by the European Society of Intensive Care, , Authors/Task Force Members, , Nieminen, M. S., Bohm, M., Cowie, M. R., Drexler, H., Filippatos, G. S., Jondeau, G., Hasin, Y., Lopez-Sendon, J., Mebazaa, A., Metra, M., Rhodes, A., Swedberg, K., ESC Committee for Practice Guidelines, , Priori, S. G., Garcia, M. A. A., Blanc, J.-J., Budaj, A., Cowie, M. R, Dean, V., Deckers, J., Burgos, E. F., Lekakis, J., Lindahl, B., Mazzotta, G., Morais, J., Oto, A., Smiseth, O. A., Document Reviewers, , Garcia, M. A. A., Dickstein, K., Albuquerque, A., Conthe, P., Crespo-Leiro, M., Ferrari, R., Follath, F., Gavazzi, A., Janssens, U., Komajda, M., Morais, J., Moreno, R., Singer, M., Singh, S., Tendera, M., Thygesen, K. (2005). Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: The Task Force on Acute Heart Failure of the European Society of Cardiology. Eur Heart J 26: 384-416 [Full Text]  
• Smull, D. L., Jorde, U. P. (2005). Concomitant use of nesiritide and milrinone in decompensated congestive heart failure. Am J Health Syst Pharm 62: 291-295 [Full Text]  
• Sheikh-Taha, M. (2005). Intermittent nesiritide therapy in outpatients with chronic heart failure. Am J Health Syst Pharm 62: 196-198 [Full Text]  
• Lisy, O., Redfield, M. M., Schirger, J. A., Burnett, J. C. Jr. (2005). Atrial BNP endocrine function during chronic unloading of the normal canine heart. Am. J. Physiol. Regul. Integr. Comp. Physiol. 288: R158-R162 [Abstract] [Full Text]  
• Witteles, R., Matsuda, K., Fowler, M. B. (2004). B-Type Natriuretic Peptide Is Effective Therapy before Care. ANN INTERN MED 141: 895-895 [Full Text]  
• Kawakami, R., Saito, Y., Kishimoto, I., Harada, M., Kuwahara, K., Takahashi, N., Nakagawa, Y., Nakanishi, M., Tanimoto, K., Usami, S., Yasuno, S., Kinoshita, H., Chusho, H., Tamura, N., Ogawa, Y., Nakao, K. (2004). Overexpression of Brain Natriuretic Peptide Facilitates Neutrophil Infiltration and Cardiac Matrix Metalloproteinase-9 Expression After Acute Myocardial Infarction. Circulation 110: 3306-3312 [Abstract] [Full Text]  
• Samuels, L. E., Holmes, E. C., Letwin, L. (2004). Nesiritide as an adjunctive therapy in adult patients with heart failure undergoing high-risk cardiac surgery. J. Thorac. Cardiovasc. Surg. 128: 627-629 [Full Text]  
• Tran, K. L., Lu, X., Lei, M., Feng, Q., Wu, Q. (2004). Upregulation of corin gene expression in hypertrophic cardiomyocytes and failing myocardium. Am. J. Physiol. Heart Circ. Physiol. 287: H1625-H1631 [Abstract] [Full Text]  
• Shlipak, M. G., Massie, B. M. (2004). The Clinical Challenge of Cardiorenal Syndrome. Circulation 110: 1514-1517 [Full Text]  
• Wang, D. J., Dowling, T. C., Meadows, D., Ayala, T., Marshall, J., Minshall, S., Greenberg, N., Thattassery, E., Fisher, M. L., Rao, K., Gottlieb, S. S. (2004). Nesiritide Does Not Improve Renal Function in Patients With Chronic Heart Failure and Worsening Serum Creatinine. Circulation 110: 1620-1625 [Abstract] [Full Text]  
• Pan, S., Gulati, R., Mueske, C. S., Witt, T. A., Lerman, A., Burnett, J. C. Jr., Simari, R. D. (2004). Gene transfer of a novel vasoactive natriuretic peptide stimulates cGMP and lowers blood pressure in mice. Am. J. Physiol. Heart Circ. Physiol. 286: H2213-H2218 [Abstract] [Full Text]  
• Schamberger, M. S. (2004). Is There a Use for Nesiritide in Pediatric Patients?. J Intensive Care Med 19: 171-173  
• Schmitt, M., Gunaruwan, P., Payne, N., Taylor, J., Lee, L., Broadley, A. J.M., Nightingale, A. K., Cockcroft, J. R., Struthers, A. D., Tyberg, J. V., Frenneaux, M. P. (2004). Effects of Exogenous and Endogenous Natriuretic Peptides on Forearm Vascular Function in Chronic Heart Failure. Arterioscler. Thromb. Vasc. Bio. 24: 911-917 [Abstract] [Full Text]  
• DiDomenico, R. J, Park, H. Y, Southworth, M. R., Eyrich, H. M, Lewis, R. K, Finley, J. M, Schumock, G. T (2004). Guidelines for Acute Decompensated Heart Failure Treatment. The Annals of Pharmacotherapy 38: 649-660 [Abstract] [Full Text]  
• van Rooij, E., Doevendans, P. A., Crijns, H. J.G.M., Heeneman, S., Lips, D. J., van Bilsen, M., Williams, R. S., Olson, E. N., Bassel-Duby, R., Rothermel, B. A., De Windt, L. J. (2004). MCIP1 Overexpression Suppresses Left Ventricular Remodeling and Sustains Cardiac Function After Myocardial Infarction. Circ. Res. 94 : e18-e26 [Abstract] [Full Text]  
• Butler, J., Emerman, C., Peacock, W. F., Mathur, V. S., Young, J. B. (2004). The efficacy and safety of B-type natriuretic peptide (nesiritide) in patients with renal insufficiency and acutely decompensated congestive heart failure. Nephrol Dial Transplant 19: 391-399 [Abstract] [Full Text]  
• de Denus, S., Pharand, C., Williamson, D. R. (2004). Brain Natriuretic Peptide in the Management of Heart Failure: The Versatile Neurohormone. Chest 125: 652-668 [Abstract] [Full Text]  
• Dorn, G. W. II, Molkentin, J. D. (2004). Manipulating Cardiac Contractility in Heart Failure: Data From Mice and Men. Circulation 109: 150-158 [Full Text]  
• Prahash, A., Lynch, T. (2004). B-Type Natriuretic Peptide: A Diagnostic, Prognostic, and Therapeutic Tool in Heart Failure. Am J Crit Care 13: 46-53 [Abstract] [Full Text]