Perspectives
B-type natriuretic peptide levels: A potential novel “white count” for congestive heart failure*

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Abstract

Finding a simple blood test to aid in the diagnosis and treatment of patients with congestive heart failure could have a favorable impact on the costs associated with the disease. B-type natriuretic peptide (BNP) is synthesized in the cardiac ventricles, and its level correlates with left ventricular pressure, amount of dyspnea, and the state of neurohormonal modulation, thus making peptide the first potential “white count” for heart failure. Data indicate that serial point-of-care testing of BNP should be helpful in patients presenting to urgent care clinics with dyspnea. BNP may also serve as a screen for patients referred for echocardiography. A low BNP level makes left ventricular dysfunction (both systolic and diastolic) highly unlikely. BNP may also provide an effective means of improving in-hospital management of patients admitted with decompensated congestive heart failure. In some cases, BNP level observations may obviate the need for invasive hemodynamic monitoring and, when such monitoring is used, may help tailor treatment of the decompensated patient. Finally, the role of BNP in the outpatient cardiac or primary care clinic may be one of critical importance in titration of therapies as well as in assessing the state of neurohormonal compensation of the patient.

Section snippets

Searching for the “white cell count” for heart failure

CHF is characterized by complicated cardiorenal, hemodynamic, and neurohormonal alterations (3). Increased levels of vasoconstrictor neurohormonal factors such as norepinephrine, angiotensin II, endothelin 1, interleukin (IL)-β, and tumor necrosis factor (TNF)-α have been found to be significant prognostic predictors in CHF, suggesting an important role of these vasoconstrictors in the pathogenesis of CHF 4, 5, 6, 7. In some cases, antagonizing these vasoconstrictors has led to improvements in

B-type natriuretic peptide

BNP is a 32-amino acid polypeptide containing a 17-amino acid ring structure common to all natriuretic peptides (19). Unlike ANP, whose major storage sites include the atria and ventricles, the major source of plasma BNP is cardiac ventricles. This suggests that BNP may be a more sensitive and specific indicator of ventricular disorders than other natriuretic peptides 20, 21. Because ANP is contained in storage granules, even a minor stimulus such as exercise can trigger a significant release

BNP levels in normal individuals and patients with CHF

BNP levels increase with age. Mean BNP levels are 26.2 ± 1.8 pg/mL for patients aged 55 to 64 years, 31.0 ± 2.4 pg/mL for those aged 65 to 74 years, and 63.7 ± 6 pg/mL for patients 75 years and older (P <.001; data on file with Food and Drug Administration [FDA], Biosite Diagnostics, San Diego, CA). Additionally, women without CHF tend to have somewhat higher BNP values than men of the same age group, with women 75 years and older having a mean BNP level of 76.5 ± 3.5 pg/mL. Although the reason

BNP and NYHA classification

Although the New York Heart Association (NYHA) classification correlates with symptoms as well as mortality in patients with heart failure, the fact that such a subjective classification is still the major means used to describe the clinical condition of patients with heart failure underlies the need for more objective surrogates. BNP is significantly correlated with hemodynamic parameters such as right atrial pressure, pulmonary capillary wedge pressure, and left ventricular end-diastolic

What should the cutoff for BNP be to diagnose CHF?

Receiver-operated characteristic (ROC) curves (data on file; Biosite Diagnostics) suggest that a BNP cut point of 100 pg/mL allows for the increased levels found with advancing age and provides an excellent ability to discriminate CHF from non-CHF subjects. This level shows a sensitivity from 82.4% for CHF in general up to more than 99% for NYHA class IV. The BNP test specificity exceeds 95% when patients are compared with all CHF patients and 93% in all subsets studied. In practice, both a

Point-of-care testing of BNP

Point-of-care (POC) testing allows diagnostic assays to be performed in locations such as the emergency department or intensive care unit where treatment decisions are made and care is delivered based on the results of the assays. Presently, POC immunoassays for cardiac markers appear to identify patients with ischemia and infarction quicker than standard laboratory-based platforms 28, 29. A rapid BNP immunoassay was recently approved by the FDA (Triage Cardiac; Biosite Diagnostics, San Diego,

Utility of BNP in the diagnosis of CHF in the acute setting

Because patients with left ventricular dysfunction have improved survival and well-being while receiving medications such as angiotensin-converting enzyme (ACE) inhibitors and β-blockers 8, 9, it is imperative to make the correct diagnosis as early in the course of the disease as possible. For acutely ill patients presenting to the emergency department, a misdiagnosis could place the patients at risk for both morbidity and mortality (30). Therefore, the emergency department diagnosis of CHF

POC testing of BNP in the emergency department setting

We recently completed a pilot study in which a POC rapid test for BNP was used on 250 patients presenting to the San Diego VA Healthcare system urgent-care area with the chief complaint of dyspnea (35). Associated symptoms could be edema, weight gain, cough, or wheezing. Patients whose dyspnea was clearly not caused by CHF (trauma, cardiac tamponade) were excluded, as were patients whose dyspnea was secondary to acute coronary syndromes. Elements from the history, physical examination, reports

BNP as a screen of left ventricular dysfunction

BNP has been used to a limited extent as a screening procedure in primary-care settings and in this venue has been shown to be a useful addition in the evaluation of possible CHF 38, 39. In a community-based study with 1653 subjects undergoing cardiac screening, the negative predictive values of BNP of 18 pg/mL was 97% for left ventricular systolic dysfunction (38). In a study of 122 consecutive patients with suspected new heart failure referred by general practitioners to a rapid-access heart

Can BNP serve as a surrogate end point for the treatment of heart failure?

Affecting 2% of the population, CHF is the fourth leading cause of adult hospitalizations in the United States and the most frequent cause of hospitalization in patients older than 65 years 1, 45, 46. Patients who are admitted to the hospital with decompensated heart failure often have improvement in symptoms with the various treatment modalities available, but there has been no good way to evaluate the long-term effects of the short-term treatment. Indeed, in-hospital mortality and readmission

BNP in patients admitted for decompensated CHF

In a pilot study, we followed the course of 72 patients admitted with decompensated NYHA class III-IV CHF, measuring BNP levels on a daily basis (47). We then determined association between initial BNP measurement and the predischarge or premoribund BNP measurement and subsequent adverse outcomes (defined as death and 30-day readmission).

Of the 72 patients admitted with decompensated CHF, 22 end points occurred (death, n = 13; readmission, n = 9). In these 22 patients, BNP levels increased

BNP and hemodynamic monitoring

Swan-Ganz catheterization in patients with decompensated heart failure may be falling out of favor, not just because of its expense and its risks, but because tailored therapy using hemodynamic monitoring has little objective basis to gauge improvement that correlates with the short-term outcomes of mortality and readmission (48). In a pilot study, hemodynamic measurements (pulmonary capillary wedge pressure, cardiac output, right atrial pressure, and systemic vascular resistance) along with

What accounts for rapid changes in BNP levels with therapy?

Other investigators have shown that treatment of patients with high ventricular filling pressures is associated with a decrease in BNP levels (18); we now show that the decrease in BNP is both rapid and finite, with an average drop of 33 pg h during active treatment. This rapid decrease can be explained by a combination of a short half-life of BNP (22 minutes) as well as falling wedge pressures, signaling a decrease in synthesis (50). Also important is that improved renal blood flow

Can BNP assist in tailoring therapy in patients with Swan-Ganz catheters in place?

Many reports have suggested that “tailored vasodilation,” aimed at normalizing pulmonary artery wedge pressure and systemic vascular resistance in CHF, results in a better clinical outcome than empiric treatment alone (50). While the general goal is a pulmonary capillary wedge pressure of 15 mm Hg, Steimle et al (51) suggest that additional benefit might be accrued by continuing treatment once an ideal wedge pressure is observed, so as to “reset” the left ventricle. Withdrawal of

The possible utility of BNP in the heart failure clinic

The correlation between the decrease in BNP level and the patient's improvement in symptoms (and subsequent outcome) during hospitalization suggests that BNP-guided treatment might also make “tailored therapy” effective in an outpatient setting such as a primary care or cardiology clinic. The Australia-New Zealand Heart Failure Group analyzed plasma neurohormones for prediction of adverse outcomes and response to treatment in 415 patients with left ventricular dysfunction randomly assigned to

Conclusions

Finding a simple blood test that would aid in the diagnosis and management of patients with CHF would clearly have a favorable impact on the costs associated with the disease. BNP, which is synthesized in the cardiac ventricles and correlates with left ventricular pressure, amount of dyspnea, and the state of neurohormonal modulation, is the first potential “white count” for heart failure. The fact that a POC rapid assay for BNP has recently been approved by the FDA gives the clinician an

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    *

    Reprint requests: Alan Maisel, MD, VAMC Cardiology 111-A, 3350 La Jolla Village Dr, San Diego, CA 92161.

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