Each year around 20,000 patients die after surgery in the UK, although the exact total is unclear. The most common causes of death involve the heart, including heart attack or heart failure. New data, from research using a sensitive blood test, suggest that ~10% of surgical patients suffer damage to the heart muscle (myocardial injury) and are more likely to die. This phenomenon is poorly understood. Urgent research is needed to find out how these complications arise and to develop new treatments to make surgery safer. Until recently some opinion leaders supported giving surgical patients beta-blockers (drugs which primarily lower heart rate). This reduced heart attacks after surgery, but was later found to increase the risk of stroke and death. The reason for this is unknown. One explanation is that elevated heart rate puts strain on the heart, increasing the demand for oxygen, which leads to damage. However, our understanding of how heart rate around the time of surgery relates to myocardial injury is incomplete. Heart rate during surgery has only been examined in a few studies. These looked at general cardiac complications, such as heart attacks, but did not use blood tests to look for myocardial injury. Heart rate before surgery has been linked to outcomes after cardiac operations, but this has not been fully investigated in non-cardiac surgery. Heart rate change during exercise may also be associated with surgical outcomes. However, the evidence is inconsistent. It is assumed that a fast heart rate before or during surgery is associated with myocardial injury. However, little evidence supports this assertion. In order to reduce cardiac complications after surgery, we must have a clear idea of the mechanism of myocardial injury. Understanding the role of heart rate before and during surgery is a crucial step in this process. This work will address an important unanswered question: are changes in heart rate associated with myocardial injury after surgery? Aim: To determine if patients with myocardial injury after surgery share common heart rate characteristics. Objectives: 1. Determine whether patterns of heart rate before or during surgery are associated with subsequent myocardial injury, and to define 'safe' heart rate ranges. 2. Investigate associations between exercise-induced changes in heart rate before surgery and subsequent myocardial injury. 3. Repeat analyses using major cardiac complications as an alternative endpoint to make this work comparable to other studies in the field. 4. Consider possible associations between myocardial injury and long-term outcomes. Methods: These objectives can only be addressed using large multi-centre datasets. Our group has unique access to four studies of surgical patients, making me ideally placed to answer these questions. Much of my work so far has involved collecting additional data for these studies, and adapting the datasets for use as part of my PhD. I will analyse these data using sophisticated statistical modelling. I will develop data management skills, learn complex statistical techniques and continue to conduct exercise tests for the METS study. I will be supported by a full-time statistician. Applications and benefits: 1. Develop a new model for identifying patients at risk of myocardial injury after surgery using pre-operative heart rate at rest and during exercise. This could enhance pre-operative assessment and improve clinical outcomes. 2. Improve clinical care by defining 'safe' heart rate ranges. Clinicians would be better able to identify patients at risk of myocardial injury and target therapy to control heart rate. 3. Develop new treatments to reduce myocardial injury. Heart rate targets could be used in two ways. (a) To improve drug dosing in clinical trials of heart rate treatments during surgery. (b) To improve recruitment to clinical trials by selecting the patients most at risk of myocardial injury.