Abstract
Background: Accurate perioperative cardiovascular risk stratification remains challenging in patients undergoing noncardiac surgery. Although treadmill testing (TMT) is widely used for functional assessment, its ability to identify truly high-risk patients is limited. Natriuretic peptides reflect integrated myocardial stress and may provide complementary prognostic information, particularly in patients with abnormal functional test results. Methods: In this prospective multicenter observational study, 178 patients with at least one Revised Cardiac Risk Index risk factor undergoing noncardiac surgery were included. All patients underwent preoperative TMT and had available N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements. The primary endpoint was 30-day major adverse cardiac events (MACE), defined as a composite of cardiac death, nonfatal myocardial infarction, myocardial injury after noncardiac surgery, pulmonary edema with heart failure, and clinically significant arrhythmias. Incremental prognostic value was assessed using the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI), with internal validation using bootstrap resampling. Results: At 30 days, 26 patients (14.6%) experienced MACE, of whom seven experienced more than one event. Log-transformed NT-proBNP was independently associated with perioperative events in parsimonious multivariable models. Elevated NT-proBNP, particularly NT-proBNP ≥ 1000 pg/mL, was independently associated with perioperative events after multivariable adjustment. Importantly, the incremental prognostic value of NT-proBNP was most pronounced in patients with a positive TMT, in whom NT-proBNP improved risk discrimination (ΔAUC = +0.09) and reclassification (NRI = 1.00). In contrast, among patients with a negative TMT, the additional prognostic contribution of NT-proBNP was modest and not statistically significant. Subgroup findings should be interpreted cautiously, given the limited number of events. Conclusions: Preoperative NT-proBNP provides modest but independent incremental prognostic value beyond treadmill testing, with the greatest impact observed in patients with positive TMT results. Although improvements in discrimination were moderate, NT-proBNP may help refine perioperative risk assessment in selected intermediate- to high-risk patients. These findings support a complementary biomarker-based approach to MACE.