Glutamate infusion reduces myocardial dysfunction after coronary artery bypass grafting according to NT-proBNP: summary of two randomized controlled trials (GLUTAMICS I-II)

Glutamate is reported to enhance 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 almost doubled to 47% compared to the cohort used for sample size estimation, and a significant effect on postoperative NT-proBNP rise was only observed in patients without diabetes. Our aim was to summarize pooled NT-proBNP results from the GLUTAMICS trials and address the impact of diabetes. Data from two prospective, randomized, double-blind multicenter trials with similar inclusion criteria and endpoints were pooled. Patients underwent CABG ± valve procedure and had left ventricular ejection fraction ≤0.30 or EuroSCORE II ≥ 3.0 with at least one cardiac risk factor. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h was started 10-20 minutes before reperfusion and continued for 150 minutes. The primary endpoint was the difference between preoperative and day-3 postoperative NT-proBNP levels. 451 patients, 224 receiving glutamate and 227 controls, fulfilled inclusion criteria. Glutamate was associated with a reduced primary endpoint (5344 ± 5104 ng/L vs. 6662 ± 5606 ng/L; p=0.01). Postoperative mortality ≤30days was 0.9% vs. 3.5% (p=0.11), and stroke ≤24 h was 0.4% vs. 2.6% (p=0.12). No adverse events related to glutamate were detected. A significant interaction regarding the primary endpoint was only detected between glutamate and insulin-treated diabetes (p = 0.04). Among patients without insulin-treated diabetes, the primary endpoint was 5047 ± 4705 ng/L vs. 7001 ± 5830 ng/L (p=0.001). Infusion of glutamate reduced postoperative rise in NT-proBNP after CABG in medium to high-risk patients. A significantly blunted effect was observed only in insulin-treated diabetes patients. NCT02592824, https://clinicaltrials.gov/ct2/show/NCT02592824