Glutamate Infusion Reduces Myocardial Dysfunction after Coronary Artery Bypass Grafting According to NT-proBNP: Summary of 2 Randomized Controlled Trials (GLUTAmate for Metabolic Intervention in Coronary Surgery [GLUTAMICS I-II])

• Background: Glutamate is reported to enhance the recovery of oxidative metabolism and contractile function of the heart after ischemia. The effect appears to be blunted in diabetic hearts. Elevated plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) reflects myocardial dysfunction. In the GLUTAmate for Metabolic Intervention in Coronary Surgery (GLUTAMICS) II trial, the proportion of patients with diabetes had nearly doubled to 47% compared with the cohort used for sample size estimation, and a significant effect on the postoperative rise in NT-proBNP was only observed in patients without diabetes. Objective: We aimed to summarize the pooled NT-proBNP results from both GLUTAMICS trials and address the impact of diabetes. Methods: Data from 2 prospective, randomized, double-blind multicenter trials with similar inclusion criteria and endpoints were pooled. Patients underwent a coronary artery bypass grafting (CABG) +/- valve procedure and had a left-ventricular ejection fraction of <= 0.30 or a European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) of >= 3.0 with at least 1 cardiac risk factor. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h was started 10-20 min before reperfusion and continued for 150 min. The primary endpoint was the difference between pre-operative and day 3 postoperative NT-proBNP levels. Results: A total of 451 patients, 224 receiving glutamate and 227 controls, fulfilled the inclusion criteria. Glutamate was associated with a reduced primary endpoint (5344 +/- 5104 ng/L and 6662 +/- 5606 ng/L in glutamate and control groups, respectively; P = 0.01). Postoperative mortality at <= 30 d was 0.9% and 3.5% (P = 0.11), whereas stroke at <= 24 h was 0.4% and 2.6% in glutamate and control groups, respectively (P = 0.12). No adverse events related to glutamate were observed. A significant interaction regarding the primary endpoint was only detected between glutamate and insulin -treated diabetes groups (P = 0.04). Among patients without insulin-treated diabetes, the primary endpoint was 5047 +/- 4705 ng/L and 7001 +/- 5830 ng/L in the glutamate and control groups, respectively (P = 0.001). Conclusions: Infusion of glutamate reduced the postoperative rise in NT-proBNP after CABG in medium-to high-risk patients. A significantly blunted effect was observed only in insulin-treated patients with diabetes. Clinical trial details: This trial was registered at www.clinicaltrials.gov as NCT02592824.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kirurgi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Surgery (hsv//eng)

Nyckelord

glutamate; heart failure; cardiac surgery; coronary artery disease; postoperative complications

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