For the entire cohort, the use of BNP (with a cutoff point of 100 pg/mL) would have improved the ED physician’s assessment from 74% diagnostic accuracy to 81%, which is statistically significant. Most important, in those patients initially given an intermediate likelihood of CHF, BNP results correctly classified 75% of these patients and rarely missed ADHF cases (<10%).
Atrial fibrillation. Since the original trials that established a BNP cutoff of 100 pg/mL for determining the presence of ADHF, several adjustments have been suggested. The presence of atrial fibrillation has been shown to increase BNP values independent of cardiac filling pressures. Breidthardt et al examined patients with atrial fibrillation presenting with dyspnea.4 In their analysis, using a cutoff of 100 pg/mL remained robust in identifying patients without ADHF. However, in the 100 pg/mL-500 pg/mL range, the test was not able to discriminate between atrial fibrillation and ADHF. Values greater than 500 pg/mL proved accurate in supporting the diagnosis of ADHF.
Renal failure. Renal dysfunction also elevates BNP levels independent of filling pressures. McCullough et al re-examined data from their Breathing Not Properly Multinational Study and found that the glomerular filtration rate (GFR) was inversely related to BNP levels.5 They recommend using a cutoff point of 200 pg/mL when the GFR is below 60 mg/dL. Other authors recommend not using BNP levels to diagnose ADHF when the GFR is less than 60 mg/dL due to the lack of data supporting this approach. Until clarified, clinicians should be cautious of interpreting BNP elevations in the setting of kidney disease.
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Obesity. Obesity has a negative effect on BNP levels, decreasing the sensitivity of the test in these patients.6 Although no study defines how to adjust for body mass index (BMI), clinicians should be cautious about using a low BNP to rule out ADHF in a dyspneic obese patient.
Historical BNP values. If historical BNP values are available, studies of biological variation have shown that an increase to 123% from 66% from baseline is representative of a clinically meaningful increase in cardiac filling pressures. Less significant changes could merely represent biological variation and should be cautiously interpreted.7
Cost effectiveness. The cost effectiveness of using BNP measurements in dyspneic ED patients has been examined as well. Mueller et al found in a Swiss hospital that BNP testing was associated with a 25% decrease in treatment cost, length of stay (LOS), and ICU usage.8 However, LOS is significantly longer in Switzerland compared with the U.S., and given that much of the cost savings was attributed to reducing LOS, it is not possible to extrapolate these data to the U.S. health system. More evidence is needed to truly evaluate the cost effectiveness of BNP testing.
Serial BNP testing. Once a patient has been diagnosed with ADHF and admitted to the hospital, diuretics are indicated with the goal of achieving euvolemia. The bedside assessment of volume status remains a difficult and inexact science, and failure to appropriately remove fluid is associated with readmissions. Conversely, overdiuresis with a concomitant rise in creatinine has been associated with increased morbidity and mortality.
Several studies have shown that the reduction of volume associated with diuretic administration is coupled with a rapid decrease in BNP levels. Therefore, serial BNP measurement has been evaluated as a tool to guide the daily assessment of volume status in patients admitted with ADHF. Unfortunately, frequent measurements of BNP reveal that a great deal of variance, or “noise,” is present in these repeat measurements. Data do not clearly show how to incorporate serial BNP measurements into daily diuretic management.9