Background: Glutamate, a key intermediate in myocardial metabolism, may enhance myocardial recovery after ischemia and possibly reduce the incidence and severity of postoperative heart failure in coronary artery bypass surgery (CABG). N-terminal pro-B-type natriuretic peptide (NT-proBNP) can be used to assess postoperative heart failure (PHF) after CABG. Our hypothesis was that glutamate enhances myocardial recovery in post-ischemic heart failure and, therefore, will be accompanied by a mitigated postoperative increase of NT-proBNP.
Methods: Substudy of the GLUTAmate for Metabolic Intervention in Coronary Surgery (GLUTAMICS) trial (ClinicalTrials.gov Identifier: NCT00489827) a prospective triple-center double-blind randomized clinical trial on 399 patients undergoing CABG with or without concomitant procedure for acute coronary syndrome at three Swedish Cardiac Surgery centres (Linköping, Örebro, and Karlskrona) from May 30, 2007 to November 12, 2009. Patients were randomly assigned to intravenous infusion of 0.125 M L-glutamic acid or saline (1.65 mL/kg of body weight per hour) intraoperatively and postoperatively. Plasma NT-proBNP was measured preoperatively, the first (POD1) and third postoperative morning (POD3). A Clinical Endpoints Committee, blinded to both intervention and NT-proBNP used prespecified criteria to diagnose PHF. The primary endpoints were the absolute levels of postoperative NT-proBNP and the difference between preoperative and postoperative levels of NT-proBNP.
Results: Overall no significant difference was detected in postoperative NT-proBNP levels between groups. However, in high-risk patients (upper quartile of EuroSCORE II ≥ 4.15; glutamate group n = 56; control group n = 45) glutamate was associated with significantly lower postoperative increase of NT-proBNP (POD3-Pre: 3900 [2995-6260] vs. 6745 [3455-12,687] ng•L-1, p = 0.012) and lower NT-proBNP POD3 (POD3: 4845 [3426-7423] vs. 8430 [5370-14,100] ng•L-1, p = 0.001). After adjusting for significant differences in preoperative demographics, NT-proBNP POD3 in the glutamate group was 0.62 times of that in the control group (p = 0.002). Patients in the glutamate group also had shorter ICU stay (21 [19-26] vs. 25 [22-46] h, p = 0.025) and less signs of myocardial injury (Troponin T POD3 (300 [170-500] vs. 560 [210-910] ng•L-1, p = 0.025).
Conclusions: Post hoc analysis of postoperative NT-proBNP suggests that intravenous infusion of glutamate may prevent or mitigate myocardial dysfunction in high-risk patients undergoing CABG. Further studies are necessary to confirm these findings. Trial registration Swedish Medical Products Agency 151:2003/70403 (prospectively registered with amendment about this substudy filed March 17, 2007). ClinicalTrials.gov Identifier: NCT00489827 (retrospectively registered) https://clinicaltrials.gov/ct2/show/NCT00489827?term=glutamics&draw=1&rank=1.
Keywords: Coronary artery bypass surgery; Glutamic acid; Heart failure; Natriuretic peptide; Postoperative care.