Stress-delta B-type Natriuretic Peptide Levels as a Test for Inducible Myocardial Ischemia: A Systematic Review and Meta-Analysis

Background Cardiac ischemia induces myocardial dysfunction and ventricular wall stretch, which causes the release of B-type natriuretic peptide (BNP) into the bloodstream. However, it is unclear whether inducible ischemia produces a significant change in BNP levels (“stress delta-BNP”). The objective of this study was to determine the utility of stress-delta BNP levels and its precursor NT-proBNP for detecting inducible myocardial ischemia during cardiac stress testing. Methods We conducted a systematic review and meta-analysis. We searched PubMed, EMBASE, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Ovid. Studies examining the changes in levels of BNP and its precursor, N-terminal pro-B-type natriuretic peptide (NT-proBNP), after an exercise cardiac stress test were included. Two reviewers independently analyzed titles and abstracts. Abstracts that did not provide enough information regarding eligibility criteria were kept for full-text evaluation. The same two reviewers also performed data extraction for analyses. Any disagreement was resolved by a consensus and, if it persisted, by a third reviewer adjudication. We report the median and mean values in studies in the order of sample size. Results A total of 15 studies met the inclusion criteria. Nine studies reported results in medians and six studies reported results in means. Of the nine studies, five assessed BNP alone, three assessed NT-proBNP, and one assessed both. Due to the non-normal distribution of results in these studies, they could not be meta-analyzed. Of the six studies that reported results in means, three assessed BNP and three assessed NT-proBNP. The standardized difference between normal and ischemic patients' stress-delta BNP values was -0.39 (95% confidence interval (CI): -0.61; -0.17) in a fixed-effects model and -0.73 (95% CI: -1.72; 0.28) in the random-effects model with high heterogeneity (I^2 = 94%, Q test P = 0.001). For NT-proBNP, the meta-analysis model showed no significant difference between the stress-delta test for ischemic and normal patients (standardized mean difference (SMD): -0.02, 95% CI: -0.31; 0.28). Patients without inducible ischemia appeared to have a lower baseline BNP and NT-proBNP compared to patients with inducible ischemia by stress testing. Although some studies report higher stress-delta BNP in the ischemic group, this pattern was not seen consistently across studies. There was high heterogeneity across studies which was not robust to sensitivity analysis. A random-effects model failed to find statistically significant differences in stress-delta BNP or NT-proBNP. Conclusions We failed to find a relationship between stress-delta BNP or NT-proBNP and the presence or absence of ischemia. This may be due to high heterogeneity in the underlying studies.