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Original Article

Natriuretic Peptide-Guided Management of Acutely Destabilized Heart Failure: Rationale and Treatment Algorithm

Bhardwaj, Anju MD; Januzzi, James L. Jr MD

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Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine: December 2009 - Volume 8 - Issue 4 - p 146-150
doi: 10.1097/HPC.0b013e3181c4a0c6
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Abstract

The advent of cardiac biomarkers over the last few decades has opened a new horizon to the diagnosis and management of heart failure.1 In the following article, we discuss the use of natriuretic peptides to monitor the treatment of patients presenting with acutely destabilized heart failure (ADHF), and derive a suggested algorithm for patient management based on this background.

HISTORICAL PERSPECTIVE OF NATRIURETIC PEPTIDES

The endocrine function of the heart was first demonstrated in 1981, when de Bold and colleagues demonstrated increased sodium and water excretion after the infusion of atrial muscle extracts in rats.2 In 1984, Kangwa et al isolated a 28 amino acid peptide, shown to have potent natriuretic, diuretic, and vasorelaxant activity.3 Subsequently, another natriuretic factor was extracted from porcine brain, and named “brain” natriuretic peptide. In recognition of its primary cardiovascular source of production and effect, this peptide was subsequently renamed as B-type natriuretic peptide (BNP).1,3

PATHOPHYSIOLOGY OF RELEASE, AND ACTION OF NATRIURETIC PEPTIDES

There are many well-described triggers for release of natriuretic peptides. Among the best known is an increase in intracardiac volume or pressure; however, several other important cardiovascular causes of synthesis and release of these peptide exist, and are worthy of knowledge (Table 1). Among these are heart muscle disease, valvular heart disease, pulmonary artery pressure, abnormalities of heart rhythm, and even coronary ischemia.4 Thus, clinicians should be aware that elevation in natriuretic peptide does not necessarily imply volume overload.

TABLE 1
TABLE 1:
Causes of Elevated Natriuretic Peptide Levels

In the context of trigger for the synthesis and release of natriuretic peptides, cardiomyocytes produce a 134 amino acid prepropeptide.5,6 Following, a 26 amino acid signal peptide is cleaved, and subsequently released. This generates a 108 amino acid peptide, proBNP108. In normal physiologic states, proBNP108 is cleaved by endoproteases into an amino-terminal fragment (NT-proBNP) and the C-terminal portion, BNP.3,6

The physiological effects of BNP are depicted in Figure 1. The BNP causes arterial vasodilatation by relaxing vascular smooth muscle, promote diuresis and natriuresis, and also reduces the activities of the renin-angiotensin-aldosterone system and the sympathetic nervous system. It also improves diastolic relaxation and decreases myocardial fibrosis.4,5

FIGURE 1.
FIGURE 1.:
Pathophysiology of natriuretic peptides.

In contrast to BNP, NT-proBNP is not biologically active. The half-life of BNP is estimated to be about 21 minutes and that of NT-proBNP is about 70 minutes.6,7 It has recently been recognized that a large percentage of the measured circulating “BNP” and “NT-proBNP” in patients with advanced heart failure are in fact uncleaved proBNP108. Since commercially available assays are unable to differentiate proBNP108 from its cleavage fragments, it is fair to say that what is being measured is likely a mixture of cleaved and uncleaved peptide.

Clearance of the natriuretic peptides is complex. BNP is actively degraded by neutral endopeptidases (degraded BNP fragments are also detected by commercial assays for its measurement) and cleared by natriuretic peptide receptors; both BNP and NT-proBNP are also passive excreted by the kidneys with no difference in their dependence on renal function for their clearance.7

NATRIURETIC PEPTIDE TESTING FOR PATIENT EVALUATION AND TRIAGE

Evaluation of dyspneic patient may be challenging, and associated with a degree of clinician uncertainty. As shown in the Breathing Not Properly Multinational study,8 addition of BNP testing to clinical judgment in evaluation of dyspnea increased diagnostic accuracy for ADHF. Of 1586 participants presenting with acute dyspnea, 722 participants (47%) were judged to have ADHF. Clinical judgment of the evaluating physician had a sensitivity of 49% and specificity of 96%, whereas BNP, at 100 pg/mL, had a sensitivity of 90% and specificity of 73%. Diagnostic accuracy increased from 74% to 81% by adding the BNP testing to clinical judgment.7,8 In the proBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study,9 NT-proBNP testing was similarly superior to clinical judgment for diagnosis or exclusion of ADHF; like BNP, the addition of NT-proBNP to clinical judgment was the superior approach for patient evaluation.

The importance of clinical uncertainty when evaluating dyspnea was further illustrated in the PRIDE study. Among 592 patients with dyspnea, clinical uncertainty for the presence or absence of ADHF was present in 185 patients (31%), of which 103 (56%) had the diagnosis. Among those judged with uncertainty for the correct diagnosis, significant morbidity and mortality was noted; in addition, these patients tended to have longer hospital lengths of stay.10

Based on the understanding of the limitations of clinical judgment and the risk associated with delayed diagnosis of ADHF, it is reasonable to consider the hypothesis that any technology to reduce uncertainty in this setting would be accompanied by improvements in utilization and outcome. Available data would suggest that in addition to improving the accuracy for ADHF,8,9 the value of adding either BNP or NT-proBNP to the triage and management of patients in the hospital after emergency department evaluation appears sound. In the BNP for Acute Shortness of Breath Evaluation and IMPROVE-CHF studies, BNP and NT-proBNP appeared to favorably affect patient management. The BNP for Acute Shortness of Breath Evaluation Study was a prospective, randomized, controlled, single-blind study on 452 patients presenting to ED with dyspnea. Patients were randomly assigned to diagnostic strategy involving use of BNP levels versus standard clinical care, with well-matched clinical and demographic characters. It was concluded that use of BNP reduced the rate of hospitalizations (75% vs. 85%), intensive care unit admissions (15% vs. 24%) with favorable effects on median time to discharge (8 vs. 11 days), mean total cost of treatment ($5410 vs. $7264), and 30-day mortality rates (10% vs. 12%).11 Considering the financial burden on health care associated with hospitalizations secondary to heart failure, accurate and cost-effective diagnosis is of paramount importance. Follow-up analysis of patients included in Basel Study was conducted, morbidity and economic data were assessed after 360 days. Morbidity as reflected by days spent in hospital at the end of 360 days was significantly lower in BNP-guided care (12% vs. 16%). Also, total treatment cost at 360 days was significantly improved in BNP group ($10,144 vs. $12,478).12

In the multicenter IMPROVE-CHF study,13 the clinical and economic significance of using NT-proBNP in the diagnosis for patients presenting with dyspnea was studied. In this study, 500 patients presenting with dyspnea were randomized to evaluation and management guided by NT-proBNP or standard management without NT-proBNP measurement. NT-proBNP levels guided care decreased the duration of ED visits by 21%, rate of rehospitalizations over 60 days by 35%, and improved direct medical costs of ED visits, hospitalizations, and subsequent outpatient care ($6129–$5180) during this period. Also, addition of NT-proBNP to standard clinical care improved the accuracy of diagnosis of heart failure.13 Subsequent “real world” analyses have supported these randomized, prospective clinical trial. One such study compared the length of hospital stay and 60-day mortality/morbidity rates among patients admitted with ADHF before and after the implementation of NT-proBNP testing. It was observed that patients in postimplementation group had significantly reduced hospital stay and improved morbidity and mortality rates.14

Although theoretically attractive, daily measurement of either BNP or NT-proBNP has not been shown to improve diagnostic accuracy, nor speed the process of therapeutic adequacy for ADHF management.

When used clinically, BNP and NT-proBNP testing add considerably to the diagnostic evaluation of the dyspneic patient; importantly, however, as with any diagnostic test, the optimal application of BNP or NT-proBNP from a diagnostic perspective is to bear in mind the wide differential diagnosis for an elevated concentration of these biomarkers; besides ADHF, this list includes but is not limited to pulmonary embolism, myocardial disease, renal insufficiency, valvular heart disease, etc.15

With the knowledge that BNP and NT-proBNP theoretically improve clinical judgment at the point of first evaluation, validated algorithms for use of BNP or NT-proBNP for diagnosis of ADHF in the dyspneic patient have been previously published.16,17

HEART FAILURE THERAPY AND NATRIURETIC PEPTIDES

Drug therapy used in the management of ADHF is well established to decrease the concentration of natriuretic peptides.18–30 The effects of multiple therapies on BNP or NT-proBNP concentrations are depicted in Table 2.

TABLE 2
TABLE 2:
Effect on Natriuretic Peptide Values of Commonly Used Drugs for Heart Failure Management

Loop diuretics lead to excretion of salt and water, decreasing filling pressures in the heart, which in turn reduces the stretch on the cardiac myocytes caused by the volume retention in ADHF. This rapid rectification of volume overload by loop diuretics often results in rapid decrease in levels of natriuretic peptides.18–20 Accordingly, as a therapeutic agent for ADHF management, rectification of volume overload using diuretics is a prime manner to lower BNP and NT-proBNP concentrations; nonloop diuretics (such as spironolactone) tend to decrease plasma levels of natriuretic peptides as well, which is attributed not only to their relatively mild diuretic effects, but also to their hypothesized effects on left ventricular remodeling and improved diastolic function.21,22

It is important to emphasize that due to the myriad of causes of natriuretic peptide elevation, lowering of BNP or NT-proBNP by definition cannot entirely occur in most patients with ADHF using diuretics alone. Indeed, the neurohormonal derangement that follows the multiple structural abnormalities in a patient with heart failure (HF) must be addressed using other agents. In this setting, it is comforting to know that angiotensin converting enzyme inhibitors and angiotensin receptor blockers attenuate the secretion of natriuretic peptides in parallel with their benefits in HF.23–25

The response of β-blockers on circulating levels of natriuretic peptides is complex. Although vasodilating agents such as carvedilol typically cause a drop in BNP or NT-proBNP,26 it has been observed that initiation of short-acting metoprolol causes an initial increase in secretion of natriuretic peptides followed by a subsequent decrease in their concentrations, typically in the absence of destabilization of HF. This might be attributed to occult elevation of transcardiac pressures caused by β-blockers before their long-term beneficial effect on remodeling of ventricle set in.20,27

Nesiritide infusion initially causes an acute rise in BNP levels as it is impossible to differentiate between the infused and endogenous BNP, but after several hours following termination of the infusion of Nesiritide, there is a significant drop in the BNP level. In contrast, NT-proBNP levels rapidly fall in response to nesiritide infusion and may be measured during administration of the drug.28

Isosorbide dinitrate combined with hydralazine therapy, when added to the conventional treatment regimen produces regression of left ventricular remodeling and decreases the plasma BNP levels.29

Aliskiren, a direct rennin inhibitor, is also known to exert favorable neurohormonal effects and reduce the plasma concentrations of both natriuretic peptides.30

PROGNOSTIC SIGNIFICANCE OF NATRIURETIC PEPTIDES

Prognostication in patients with ADHF is difficult, and the decision to discharge patients after hospitalization due to ADHF is similarly challenging. The latter is currently determined by clinical parameters such as improvement in weight as well as resolution of symptoms, in addition to successful achievement of an adequate medication program. Often, however, these goals are somewhat arbitrary, and frequently fall short of the goal, particularly in the highest risk patients, who may not be clinically obvious at the time of hospital discharge. This leads to a rate of readmission for recurrent ADHF as high as 50% within 6 months, with a prohibitively high rate of mortality.31,32 The high morbidity and mortality rates of patients with recent ADHF poses a challenge to identify the patients at highest risk for complications, preferably prior to discharge. In this setting, it has been well-demonstrated that concentrations of BNP and NT-proBNP carry prognostic significance, predicting short- and long-term morbidity and mortality.33

In the REDHOT study,34 a multicenter study of 464 patients presenting to ED with dyspnea, Maisel et al found BNP levels at time of presentation to be a strong predictor of 90-day outcome, irrespective of clinician-judged level of risk.34 In a similar manner, Harrison et al also demonstrated that presenting BNP values were highly predictive of cardiac endpoints—-death or readmission, over the next 6 months.35

Definitive data regarding the prognostic value of the presentation NT-proBNP concentration were published by the International Collaborative of NT-proBNP investigators: among 720 patients with AHDF, NT-proBNP levels in excess of 5180 pg/mL on presentation were strongly predictive of death by 76 days (odds ratio, 5.2; 95% confidence interval [CI], 2.2–8.1; P < 0.001).36 Longer term value of NT-proBNP for prognosis was illustrated in the 1-year follow-up study from PRIDE, where an NT-proBNP in excess of 1000 pg/mL strongly predicted death in ADHF, while lower concentrations had a high negative predictive value for excluding risk of death by 1 year.37

Although presentation values are useful for prognostication, it has been definitively established that posttreatment, predischarge BNP or NT-proBNP may carry even stronger prognostic meaning.38,39 In a study by Logeart et al, serial BNP levels of patients were measured from admission to discharge in 2 samples. Subjects were monitored for 6 months, the endpoint being death or first readmission. The predischarge BNP assay was observed to be a strong and independent marker predicting death or readmission after ADHF, even more relevant than common clinical and echocardiographic parameters.38 Another small study, where 50 patients admitted with heart failure exacerbation were followed up for 6 months, showed similar results.40 Patients whose predischarge BNP levels was higher than median (321 pg/mL) had increased rates of death or readmissions.40

In a landmark study, Bettencourt et al32 evaluated 182 patients presenting with ADHF, with a measurement of NT-proBNP before and after treatment for ADHF. Concentrations of NT-proBNP were blinded to the clinicians, and discharge decision was based on clinical judgment only. Patients were classified into 3 groups based on the variations in NT-pro BNP levels during the initial admission: (1) decrease in NT-proBNP levels by 30% or more; (2) decrease/increase in NT-proBNP less than 30%; and (3) increase in NT-proBNP levels by 30% or more. Although all patients were judged to be eligible for discharge, the group of patients who had a rise of 30% or more in NT-proBNP concentration were observed to have dramatic adverse outcomes such as death or rehospitalization during the ensuing 6 months, when compared with patients who had >30% decrease in NT-proBNP, who had better outcomes.32

Lastly, more definitive data were recently reported by Cohen-Solal in a population of 1038 subjects with ADHF; in this analysis, a fall of 30% or more in BNP concentration after therapy was associated with pronounced survival, compared with “nonresponders” who had worse outcomes.41

These results strongly suggest that the variation in BNP or NT-proBNP concentrations after therapy for ADHF are independent objective predictors of therapy adequacy, and by proxy well-predict morbidity and mortality after ADHF therapy.32,40

Patients who do not have baseline BNP/NT-proBNP values available can still be monitored with therapy optimized by following treatment goals rather than percent change. In this setting, desired levels of BNP are in the range of 350 pg/mL or lower, while for NT-proBNP, the value is <4000 pg/mL.40,42

ALGORITHM FOR BNP/NT-PRO-BNP MONITORING OF ADHF THERAPY

An algorithm for BNP or NT-proBNP-based monitoring of ADHF therapy is depicted in Figure 2. A baseline measure is recommended not only for diagnostic value as outlined above, but also to serve as a starting point for therapy monitoring. As suggested, daily or more measures of BNP or NT-proBNP do not appear to add significant prognostic value, and are not likely to be cost-effective, as ADHF therapy in the early stages of hospitalization is based more on clinical goals, rather than biochemical ones. After establishment of a “baseline” BNP or NT-proBNP value, it is advisable to proceed with standard ADHF management. Following perceived “recompensation” and in preparation for hospital discharge, a second measurement of BNP or NT-proBNP is advised. Should treatment goals be reached, and a biochemical response of 30% or more is observed, such patients are at generally lower risk for discharge. On the other hand, if a rise in BNP or NT-proBNP is observed, such patients are at high risk—even in the face of apparent treatment adequacy—and discharge might be delayed, and a review of therapeutic adequacy is advised. In the absence of a “starting point” for BNP or NT-proBNP, absolute values below approximately 350 pg/mL for BNP and 4000 pg/mL for NT-proBNP following ADHF are reasonable targets.

FIGURE 2.
FIGURE 2.:
Algorithm for BNP/NT-proBNP-based monitoring of patients with acutely destabilized heart failure.

Disclosures

Dr. Bhardwaj is supported by the Dennis and Mrilyn Barry Fellowship in Cardiology. Dr. Januzzi is supported in part by the Balson Cardiac Scholar fund.

REFERENCES

1.Felker GM, Peterson JW, Mark DB. Natriuretic peptides in the diagnosis and management of heart failure. CMAJ. 2006;175:611–617.
2.de Bold AJ, Borenstein HB, Veress AT, et al. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extracts in rats. Life Sci. 1981;28:89–94.
3.Kangawa K, Matsuo H. Purification and complete amino acid sequence of human atrial natriuretic polypeptide (-hANP). Biochem Biophys Res Commun. 1984;118:131–139.
4.Mohammed AA, Januzzi JL, Jr. Natriuretic peptide guided heart failure management. Curr Clin Pharmacol. 2009;4:87–94.
5.Cowie MR, Struthers AD, Wood DA, et al. Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care. Lancet. 1997;350:1347–1351.
6.Braunwald E. Biomarkers in heart failure. NEJM. 2008;358:2148–2159.
7.Daniels LB, Maisel AS. Natriuretic peptides. J Am Coll Cardiol. 2007;50:2357–2368.
8.Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in emergency diagnosis of heart failure. NEJM. 2002;347:161–167.
9.Januzzi JL, Camargo CA, Anwaruddin S, et al. The N-terminal Pro-BNP investigation of dyspnea in the Emergency Department (PRIDE) Study. Am J Cardiol. 2005;95:948–954.
10.Green SM, Martinez-Rumayor A, Gregory SA. Clinical uncertainty, diagnostic accuracy, and outcomes in emergency department patients presenting with dyspnea. Arch Intern Med. 2008;168:741–748.
11.Mueller C, Scholer A, Laule-Kilian K, et al. Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea. NEJM. 2004;350:647–654.
12.Breidthardt T, Laule K, Strohmeyer A, et al. Medical and economic long term effects of B-type natriuretic peptide testing in patients with acute dyspnea. Clin Chem. 2007;53:1415–1422.
13.Moe GW, Howlett J, Januzzi JL, et al. N-terminal Pro-B-type natriuretic peptide testing improves the management of patients with suspected acute heart failure. Primary results of the Canadian prospective randomized multicenter IMPROVE-CHF Study. Circulation. 2007;115:3103–3110.
14.Green SM, Redmond P, Januzzi JL, et al. The impact of Amino-terminal Pro-brain natriuretic peptide testing on hospital length of stay and morbidity in patients with acute decompensated heart failure. Arch Pathol Lab Med. 2007;131:473–476.
15.Baggish AL, Kimmenade RR, Januzzi JL. The differential diagnosis of an elevated amino-terminal Pro-B-type natriuretic peptide level. Am J Cardiol. 2008;101:43–48. Review
16.Baggish AL, Cameron R, Anwaruddin S, et al. A clinical and biochemical critical pathway for the evaluation of patients with suspected acute congestive heart failure. The PRIDE Algorithm. Crit Pathw Cardiol. 2004;3:171–176.
17.Maisel A. Algorithms for using B-type natriuretic peptide levels in the diagnosis and management of congestive heart failure. Crit Pathw Cardiol. 2002;1:67–73.
18.Baggish AL, Kimmenade RR, Januzzi JL. Amino-terminal Pro-B-type natriuretic peptide testing and prognosis in patients with acute dyspnea, including those with acute heart failure. Am J Cardiol. 2008;101(suppl):49A–55A.
19.Braunschweig F, Fahrleitner-Pammer A, Mangiavacchi M, et al. Correlation between serial measurements of N-terminal pro brain natriuretic peptide and ambulatory cardiac filling pressures in outpatients with chronic heart failure. Eur J Heart Fail. 2006;8:797–803.
20.Troughton RW, Richards AM. Outpatient monitoring and treatment of chronic heart failure guided by amino-terminal Pro-B-type natriuretic peptide measurement. Am J Cardiol. 2008;101(suppl):72A–75A.
21.Tsutamoto T, Wada A, Maeda K, et al. Effect of spirinolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Coll Cardiol. 2001;37:1228–1233.
22.Rousseau MF, Gurne O, Duprez D, et al. Beneficial neurohormonal profile of spirinolactone in severe congestive heart failure: results from the rales neurohormonal substudy. J Am Coll Cardiol. 2002;40:1596–1601.
23.Kohno M, Minami M, Kano H, et al. Effect of angiotensin-converting enzyme inhibitor on left ventricular parameters and circulating brain natriuretic peptide in elderly hypertensives with left ventricular hypertrophy. Metabolism. 2000;49:1356–1360.
24.Yoshimura M, Mizuno Y, Nakayama M, et al. B-type natriuretic peptide as a marker of the effects of enalapril in patients with heart failure. Am J Med. 2002;112:716–720.
25.Latini R, Masson S, Anand I, et al. Effects of valsartan on circulating brain natriuretic peptide and norepinephrine in symptomatic chronic heart failure: the Valsartan Heart Failure Trial (Val-Heft). Circulation. 2002;106:2454–2458.
26.Sanderson JE, Chan WW, Hung YT, et al. Effect of low dose beta blockers on atrial and ventricular (B type) natriuretic factor in heart failure: a double blind, randomised comparison of metoprolol and a third generation vasodilating beta blocker. Br Heart J. 1995;74:502–507.
27.Davis ME, Richards AM, Nicholls MG, et al. Introduction of metoprolol increases plasma B-type cardiac natriuretic peptides in mild, stable heart failure. Circulation. 2006;113:977–985.
28.Fitzgerald RL, Cremo R, Gardetto N, et al. Effect of nesiritide on combination with standard therapy on serum concentrations of natriuretic peptides in patients admitted for decompensated congestive heart failure. Am Heart J. 2005;150:471–477.
29.Cohn JN, Tam SW, Anand IS, et al. Isosorbide dinitrate and hydralazine in a fixed-dose combination produces further regression of left ventricular remodeling in a well-treated black population with heart failure: results from A-HeFT. J Card Fail. 2007;13:331–339.
30.McMurray JJV, Pitt B, Latini R, et al. Effects of the oral direct renin inhibitor aliskiren in patients with symptomatic heart failure. Circ Heart Fail. 2008;1:17–24.
31.Krumholz HM, Chen YT, Wang Y, et al. Predictors of readmission among elderly survivors of admission with heart failure. Am Heart J. 2000;139:72–77.
32.Bettencourt P, Azevedo A, Pimenta J, et al. N-terminal pro-brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients. Circulation. 2004;110:2168–2174.
33.Bettencourt P, Januzzi JL. Amino-terminal pro-B-type natriuretic peptide testing for inpatient monitoring and treatment guidance of acute destabilized heart failure. Am J Cardiol. 2008;101:67–71.
34.Maisel A, Hollander JE, Guss D, et al. Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT). A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath. J Am Coll Cardiol. 2004;44:1328–1333.
35.Harrison A, Morrison LK, Krishnaswamy P, et al. B-type natriuretic peptide predicts future cardiac events in patients presenting to the emergency department with dyspnea. Ann Emerg Med. 2002;39:131–138.
36.Januzzi JL, Kimmenade RV, Lainchbury J, et al. NT-pro-BNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients. The International Collaborative of NT-proBNP Study. Eur Heart J. 2006;27:330–337.
37.Januzzi JL, Sakhuja R, O'Donoghue M, et al. Utility of amino-terminal pro- brain natriuretic peptide testing for prediction of 1-year mortality in patients with dyspnea treated in the emergency department. Arch Intern Med. 2006;166:315–320.
38.Logeart D, Thabut G, Jourdain P, et al. Predischarge B-type natriuretic peptide assay for identifying patients at high risk of re-admission after decompensated heart failure. J Am Coll Cardiol. 2004;43:635–641.
39.Hamada Y, Tanaka N, Murata K, et al. Significance of predischarge BNP on one-year outcome in decompensated heart failure—comparative study with echo-Doppler indexes. J Card Fail. 2005;11:43–49.
40.Bettencourt P, Ferreira S, Azevedo A, et al. Preliminary Data on the potential usefulness of B-type natriuretic peptide levels in predicting outcome after hospital discharge in patients with heart failure. Am J Med. 2002;113:215–219.
41.Cohen-Solal A, Logeart D, Huang B, et al. Lowered B-Type natriuretic peptide in response to levosimendan or dobutamine treatment is associated with improved survival in patients with severe acutely decompensated heart failure. J Am Coll Cardiol. 2009;53:2343–2348.
42.Olsson LG, Swedberg K, Cleland JG, et al. Prognostic importance of plasma NT-pro BNP in chronic heart failure in patients treated with a beta-blocker: results from the Carvedilol or Metoprolol European Trial (COMET). Eur J Heart Fail. 2007;9:795–801.
Keywords:

natriuretic peptides; heart failure; coronary artery disease

© 2009 Lippincott Williams & Wilkins, Inc.