Provocative biomarker stress test: stress-delta N-terminal pro-B type natriuretic peptide

Stress testing is commonly performed in emergency department (ED) patients with suspected acute coronary syndrome (ACS). We hypothesised that changes in N-terminal pro-B type natriuretic peptide (NT-proBNP) concentrations from baseline to post-stress testing (stress-delta values) differentiate patients with ischaemic stress tests from controls.

We prospectively enrolled 320 adult patients with suspected ACS in an ED-based observation unit who were undergoing exercise stress echocardiography. We measured plasma NT-proBNP concentrations at baseline and at 2 and 4  hours post-stress and compared stress-delta NT-proBNP between patients with abnormal stress tests versus controls using non-parametric statistics (Wilcoxon test) due to skew. We calculated the diagnostic test characteristics of stress-delta NT-proBNP for myocardial ischaemia on imaging.

Among 320 participants, the median age was 51 (IQR 44-59) years, 147 (45.9%) were men, and 122 (38.1%) were African-American. Twenty-six (8.1%) had myocardial ischaemia. Static and stress-deltas NT-proBNP differed at all time points between groups. The median stress-deltas at 2  hours were 10.4 (IQR 6.0-51.7) ng/L vs 1.7 (IQR -0.4 to 8.7) ng/L, and at 4  hours were 14.8 (IQR 5.0-22.3) ng/L vs 1.0 (-2.0 to 10.3) ng/L for patients with ischaemia versus those without. Areas under the receiver operating curves were 0.716 and 0.719 for 2-hour and 4-hour stress-deltas, respectively. After adjusting for baseline NT-proBNP levels, the 4-hour stress-delta NT-proBNP remained significantly different between the groups (p=0.009).

Among patients with ischaemic stress tests, static and 4-hour stress-delta NT-proBNP values were significantly higher. Further study is needed to determine if stress-delta NT-proBNP is a useful adjunct to stress testing.