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Myths in Emergency Medicine: Natriuretic Peptides Add Noise to an Already Uncertain Baseline

Spiegel, Rory MD

doi: 10.1097/01.EEM.0000482467.75035.3a
Myths in Emergency Medicine

Dr. Spiegelis a clinical instructor in emergency medicine at Stony Brook Medical Center, Department of Emergency Medicine. Visit his blog athttp://emnerd.comand follow him on Twitter @emnerd_.

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It is important to remember in moments of diagnostic uncertainty that not only does a test have to be accurate and reliable to be useful, it also must add diagnostic value above the clinician's own inherent aptitude. B-type natriuretic peptide (BNP) and its natriuretic derivatives are a classic example of such a test heralded for its isolated diagnostic properties without asking the simple question, “How does it help the physician?”

Through statistical misdirection, the distributors of natriuretic peptides have published research that has led to the integration of these assays into the workup of acute decompensated heart failure (ADHF). (J Am Coll Cardiol 2013;62[16]:e147; Eur J Heart Fail 2012;14[8]:803; Care Eur Heart J 2012;33[16]:2001.)

A recent meta-analysis sought to examine the validity of these recommendations and determine the true diagnostic accuracy of natriuretic peptides. (BMJ 2015;350:h910.) Roberts, et al., examined the clinical accuracy of BNP, NTproBNP, and MR-proANP for the diagnosis of ADHF in the emergency department. Their goal was to evaluate the low-risk criteria proposed by the 2012 European Society of Cardiology guidelines for heart failure, a BNP ≤100 ng/L, a NTproBNP, ≤300 ng/L, and a MR-proANP, ≤120 pmol/L. They also examined the utility of these assays at intermediate levels (100-500 ng/L for BNP; 300-1800 ng/L for NTproBNP; and >120 pmol/L for MR-proANP). (BMJ 2015;350:h910.)

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High Sensitivities

The authors identified 42 articles, examining 37 different cohorts that met criteria for inclusion into their meta-analysis. The authors calculated pooled test characteristics for each of the assays in question. They found that all three assays demonstrated high sensitivities at the low thresholds proposed by the European Society of Cardiology: 95 percent, 99 percent, and 95 percent, respectively.

Of course, by selecting such a low cutoff, the authors ensured that a large proportion of the patients without acute heart failure would also test positive. The specificities were a dismal 63 percent, 43 percent, and 56 percent, respectively. The specificities increased to 86 percent and 76 percent for BNP and NTproBNP when the intermediate thresholds were utilized. Of course, this came with a loss of sensitivity: 85 percent and 90 percent, respectively. (BMJ 2015;350:h910.)

The authors concluded, “The use of NTproBNP and B type natriuretic peptide at the rule-out threshold recommended by the recent European Society of Cardiology guidelines on heart failure provides excellent ability to exclude acute heart failure in the acute setting with reassuringly high sensitivity.” (BMJ 2015;350:h910.) This is a fair conclusion at face value because these assays seemed to perform moderately well at either extreme of their diagnostic spectrum. Unfortunately, these results do very little to explain the true utility of natriuretic peptides. The authors, by isolating each assay's test characteristics outside the clinical arena, have falsely inflated the value of BNP and its natriuretic derivatives.

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EP Judgment

How do natriuretic peptides perform in the clinical arena? More specifically, how well do they help the emergency physician differentiate the causes of dyspnea in the subset of patients where there is considerable diagnostic uncertainty? The assay's accuracy was 92 percent vs. the BNP values (84%) for patients in which the emergency physician was certain ADHF was not the cause of their dyspnea. Likewise, emergency physician judgment outperformed the diagnostic abilities of the BNP assay when the EP was certain the patient did have ADHF (accuracy of 95% versus 92%). (Chest 2015;148[1]:202.)

Of the 27.8 percent of patients in which the emergency physician was unclear of the diagnosis, the very group for which we would hope the BNP could provide guidance, its diagnostic accuracy was entirely unhelpful. The assay, at a cutoff of 100 ng/L in this subset of patients, demonstrated no clinical utility with a sensitivity and specificity of 79 percent and 71 percent, respectively. (CJEM 2003;5[3]:162.)

These assays are far too insensitive and nonspecific to add substantial clarity for the patients who present a diagnostic conundrum. Furthermore, we have other, more diagnostically robust tools, like point-of-care ultrasound, to assist in these challenging circumstances. (Chest 2015;148[1]:202.)

Pivetta, et al., in Chest examined the utility of POCUS in the diagnosis of ADHF. A total of 463 (46%) of the 1,005 patients enrolled received the final diagnosis of acute decompensated heart failure. The treating physician's ability to differentiate clinically cardiac from a noncardiac cause of the presenting dyspnea was exceptionally good. The physicians demonstrated a sensitivity and specificity of 85.3 percent and 90 percent, respectively.

The performance of the POCUS alone, though numerically better (sensitivity of 90.5% and a specificity of 93.5%), did not differ statistically from the physician's intrinsic diagnostic capabilities. Each performed well in isolation, but the combination of the clinical and sonographic exams significantly augmented their mutual diagnostic capabilities. The sensitivity and specificity of the physician's judgment in addition to lung ultrasound was 97 percent and 97.4 percent, respectively. More importantly was its performance when compared with the natriuretic peptides, which demonstrated a sensitivity and specificity of 85 percent and 67.1 percent, respectively. (Chest 2015;148[1]:202.)

The emergency physician is more than capable of clinically identifying patients presenting in acute decompensated heart failure a vast majority of the time. Natriuretic peptides provide little additional guidance for the few cases that cast a diagnostic dilemma. Bedside ultrasound is a swift noninvasive tool in possession of diagnostic characteristics robust enough to shift post-test probability to a degree that is clinically relevant. Now is the time to speak frankly about natriuretic peptides. They are diagnostic clutter. Natriuretic peptides add noise to an already uncertain baseline, making it more difficult to detect the signal through the already thunderous cacophony that is diagnostic uncertainty.

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