N-Terminal Pro-B-type Natriuretic Peptide Predicts Mortality after Major Lower-Limb Amputation for Peripheral Arterial Disease

AIMS: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is known to predict adverse cardiac outcomes in non-cardiac surgery. However, its prognostic role in patients undergoing major limb amputation (MLA) remains under-explored. This study aimed to evaluate the relationship between NT-proBNP levels and mortality following MLA. METHODS: A retrospective cohort study of all patients undergoing MLA at a single tertiary vascular center between 01/01/2019-31/12/2023 was performed. Demographic data, comorbidities, American Society of Anaesthesiologists (ASA) grade, frailty status, amputation level, and NT-proBNP measurements were collected. NT-proBNP-specific analyses were restricted to the 203 patients with at least one pre- or post-operative measurement (122 pre-operative, 81 post-operative). Univariable associations with 1- and 2-year mortality were assessed, followed by multivariable binary logistic regression incorporating clinically relevant covariates. RESULTS: There were 433 Amputations in 409 patients analyzed (317 [73.20%] male; median age 72 [62.40-80.30] years). There were 261 (60.30%) Below-knee amputations (BKA), 170 (39.70%) above-knee amputations (AKA). The cohort demonstrated substantial comorbidity 263 (60.70%) diabetes, 234 (54%) hypertension, 133 (30.70%) ischaemic heart disease) with ASA grade III-IV in 425 (98%) and frailty present in 407 (94%). Overall mortality was high at 8 (1.96%) at 30 days, 116 (26.80%) at 1 year and 145 (33.50%) at 2 years. A total of 209 NT-proBNP measurements were collected, of which 203 were used in the analysis (122 pre-operative, 81 post-operative). Median pre-operative NT-proBNP was 1,162 (274-3,721)ng/L, and post-operative NT-proBNP was 1,194 (496-5,966) ng/L. Pre-operative and post-operative NT-proBNP was significantly higher in non-survivors at 1 and 2 years (All P ≤ 0.016). Other univariable predictors of mortality at 1 and 2 years included amputation level, increasing age, higher ASA grade (All P < 0.0001) and ischaemic heart disease (P = 0.005). After multivariable adjustment, pre-operative and post-operative NT-proBNP remained independently associated with mortality at both 1 and 2 years as continuous variables: Pre-operative: OR 1.00010, 95% Confidence Interval (CI): 1.00003-1.00020 for both, P = 0.007 and P = 0.019 respectively; Post-operative: OR 1.00012, 95% CI: 1.00003-1.00021, P = 0.012 and P = 0.004 respectively. Furthermore, pre-operative NT-proBNP >2000 ng/L remained an independent predictor of mortality at one and 2 years after multivariable adjustment: OR: 3.90, 95% CI (1.44-10.59), P = 0.008, and OR 2.57, 95% CI (1.05-6.32), P = 0.04 respectively. CONCLUSION: Patients undergoing MLA experience very high early and medium-term mortality. Both pre-operative and post-operative NT-proBNP independently predict mortality beyond age, frailty, and amputation level, supporting its role as a powerful biomarker for peri-operative risk stratification and multidisciplinary decision-making in this high-risk population.