Postoperative heart failure (PHF) remains a major determinant of the outcome after cardiac surgery. However, characteristics of and risk factors for PHF after valve surgery have received little attention. Post-ischaemic disturbances of myocardial metabolism that may contribute to PHF and are amenable to metabolic treatment have been identified early after coronary surgery (CABG). Knowledge derived from these studies may not be applicable to other patient groups. We therefore studied myocardial energy metabolism in 20 elective patients undergoing aortic valve replacement (AVR) for isolated aortic stenosis (AS). The metabolic studies indicated that myocardial oxidative metabolism had not fully recovered when the procedure was completed. Free fatty acids were the only major substrates taken up by the heart. Signs of preoperative and postoperative metabolic adaptation with substantial uptake of glutamate, previously demonstrated in patients with coronary artery disease, were found. Postoperative infusion of glutamate, (2 mL/kg body weight and hour of 0.125 M solution) based on assessment of myocardial glutamate requirements in CABG patients, resulted in a two-fold increase in myocardial glutamate uptake and a seven-fold increase in AV differences across the leg. This was associated with a significant myocardial uptake of lactate and metabolic changes in the leg suggesting mitigation of net amino acid loss and peripheral tissue lipolysis. Characteristics of and risk factors for PHF were evaluated in 398 patients undergoing isolated AVR for AS from 1 January 1995 to 31 December 2000. These were compared with 398 patients, matched for age and sex, undergoing on-pump isolated CABG. Forty-five AVR and 47 CABG patients fulfilled criteria for PHF and these were studied in detail. PHF usually presented at weaning from cardiopulmonary bypass. After CABG it was closely associated with preoperative ischaemic events and intraoperatively acquired myocardial infarction. Potential causes and eliciting events of PHF after AVR for AS were obvious only in one-third of the patients. Risk factors for PHF after AVR for AS indicated either pre-existing myocardial dysfunction, increased right or left ventricular after-load, or intraoperatively acquired myocardial injury. PHF was associated with high early mortality after CABG, whereas the consequences of PHF after AVR for AS became evident only with time, resulting in a 42% five-year mortality. Although PHF had a different temporal impact on late mortality after CABG and AVR for AS, it emerged as the statistically most significant risk factor for mortality occurring within 5 years from surgery both after AVR for AS and after CABG. Potential implications of our findings include needs for greater focus on preoperative surveillance of patients with AS for optimal timing of surgery, mitigation of intraoperatively acquired myocardial injury and tailoring of treatment for PHF. Furthermore, the findings have implications for long-term follow up of AS patients after surgery.

Myocardial ischemia is a major cause of postoperative heart failure and adverse outcome in coronary artery bypass graft surgery (CABG). Conventional treatment of postoperative heart failure with inotropic drugs may aggravate underlying ischemic injury. Glutamate has been claimed to increase myocardial tolerance to ischemia and promote metabolic and hemodynamic recovery after ischemia. The aim of this work was to investigate if intravenous glutamate infusion given in association with CABG for acute coronary syndrome can reduce mortality and prevent or mitigate myocardial injury and postoperative heart failure. We also wanted to assess neurological safety issues, as a concern with the use of glutamate is that it may act as an excitotoxin under certain conditions.A metabolic strategy for perioperative care was assessed in an observational study on 104 consecutive patients with severe left ventricular dysfunction undergoing CABG. Based on encouraging clinical results, unsurpassed in the literature, the GLUTAMICS-trial was initiated. 861 patients undergoing CABG for acute coronary syndrome were randomly allocated to blinded intravenous infusion of L-glutamicacid solution or saline. The primary endpoint was a composite of postoperative mortality (≤30 days), perioperative myocardial infarction and left ventric ular heart failure in association with weaning from cardiopulmonary bypass. Secondary endpoints included neurological safety issues, degree of myocardial injury,postoperative hemodynamic state, use of circulatory support and cardiac mortality.The event rate was lower than anticipated and the primary endpoint did not differ significantly between the groups. Regarding secondary endpoints there were significant differences compatible with a beneficial effect of glutamate on post-ischemic myocardial recovery. The putative effect of glutamate infusion was seen in more ischemic patients (CCS class IV) and in patients with evident or anticipated LV-failure on weaning from CPB. No evidence for increased incidence of clinical or subclinical neurological injury was found. In conclusion, intravenous glutamate infusion is safe in the dosages employed and could provide a novel and important way of promoting myocardial recovery after ischemic injury.