SURGERY FOR AORTIC STENOSIS with special reference to myocardial metabolism, postoperative heart failure and long-term outcome

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 per 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. LIST OF ORIGINAL ARTICLES This thesis is based on the following papers, which are referred by their Roman numerals: [I]: Different characteristics of postoperative heart failure after surgery for aortic stenosis and coronary disease. Vánky FB , Håkanson E, Maros T, Svedjeholm R. Scand Cardiovasc J. 2004;38:152-8. [II]: Risk factors for postoperative heart failure in patients operated on for aortic stenosis. Vánky FB , Håkanson E, Tamás E, Svedjeholm R. Ann Thorac Surg 2006;81:1297-304 [III]: Influence of early postoperative heart failure on five-year survival after surgery for aortic stenosis compared with CABG. Vánky FB, Håkanson E, Svedjeholm R. Manuscript [IV]: Myocardial metabolism before and after valve replacement for aortic stenosis. Vánky FB, Håkanson E, Szabó Z, Jorfeldt L, Svedjeholm R. J Cardiovasc Surg 2006; in press [V]: Does glutamate influence myocardial and peripheral tissue metabolism after valve replacement for aortic stenosis? Vánky FB , Håkanson E, Jorfeldt L, Svedjeholm R. Clin Nutr 2006; in press [VI]: Assessment of myocardial glutamate requirements early after coronary artery bypass surgery. Vanhanen I, Svedjeholm R, Håkanson E, Joachimssom PO, Jorfeldt L, Vánky FB. Scand Cardiovasc J. 1998;32:145-152.