Peri-operative cardiac morbidity: prediction, prevention and the novel role of B-type natriuretic peptide

Cardiovascular disease is the leading cause of death in surgical patients and because of this a number of strategies have been utilised to attempt to predict the cardiac risk of surgery. Theoretically, accurate pre-operative risk stratification would allow patients at low risk to have their surgery expedited efficiently, whilst those at higher risk could have a change made to their treatment plan such as peri-operative cardiac optimisation or in some cases, modification of the operative procedure. Despite this rationale, no guidelines currently exist in the United Kingdom for the management of the surgical patient at high cardiac risk. This may partly reflect the limited methods of risk stratification currently available. Clinical scoring systems are simple and inexpensive but limited by their predictive value. Trans-thoracic echocardiography provides prognostic information but is inconsistent, adding little to clinical information alone. The most accurate methods of pre-operative cardiac risk prediction at the present time are dobutamine stress echocardiography and dipyridamole thallium scanning. However they are expensive, time consuming and have shown poor positive predictive ability, even in high risk cohorts. Few studies have studied the usefulness of biochemical markers in the prediction of post-operative cardiac events. In particular, no information was available in the literature regarding the role of B-type natriuretic peptide (BNP) in the prediction of cardiac events in non-cardiac surgical patients; despite the fact that its measurement has been shown to be an important prognostic tool in both non-surgical and cardiac surgical cohorts. In this thesis the aim was to determine whether pre-operative BNP concentration related to cardiac outcome following non-cardiac surgery; and also to determine whether measurement of other markers such as C- reactive protein (CRP) and cardiac troponin I (CTnI) would be of benefit in pre-operative cardiac risk stratification. To assess the effectiveness of plasma BNP measurement in the prediction of peri-operative cardiac morbidity a pilot study of 41 patients undergoing vascular surgery was conducted. To ensure that any post-operative rise in CTnI was due to operative stress, this was measured pre-operatively along with CRP. Median pre-operative BNP concentration was significantly higher in patients who suffered a post-operative cardiac event (cardiac death, non-fatal myocardial infarction (MI)) than in those who did not (210 (165-380) pg/ml vs. 34.5 (14-70) pg/ml, p<0.001). On the basis of these results a single-centre, prospective, observational cohort study was performed of all patients undergoing non-cardiac surgery. Of the 149 patients recruited to this study, 15 had a cardiac event. The median BNP in those patients having a cardiac event was more than ten-times higher than in those who did not (351 (127-1034) vs. 30.5 pg/ml (11-79.5), p<0.001). A BNP concentration of 108.5pg/ml was the best performing cut-off value having a sensitivity and a specificity of 87%. Although CTnI had originally been measured to ensure that any post-operative rise was due to operative stress, 3 patients had a pre-operative elevation all of whom underwent lower extremity amputation. The amputation group, and in particular those patients who had a raised pre-operative cTnI were therefore analysed further. Amputation patients in general had a high cardiac event rate (23%); however the outcome in those patients who had a raised pre-operative cTnI was particularly poor with 2 suffering a cardiac death post-operatively and one suffering a non-fatal MI. A pre-operative rise in CTnI was the only significant single predictor of peri-operative cardiac events in patients undergoing amputation (p= 0.009). Pre-operative CRP concentration was measured routinely in vascular patients. The concentration in those who had a cardiac event was significantly higher than those who did not (69 (0-260) vs. 12 (0-285), (p=0.003). The cardiac event rate rose with each logarithmic increment in CRP concentration (0-10mg/l (5.7%); 11-100mg/l (22.4%), >100mg/l (55.6%) (p=0.002). Measurement of CRP was of most potential benefit in patients undergoing aortic aneurysm surgery. In conclusion, this thesis has shown that pre-operative measurement of biochemical markers (BNP, CTnI, and CRP) can allow accurate peri-operative risk stratification. BNP concentration in particular was a sensitive and specific predictor of cardiac outcome. Careful case selection using a combination of clinical assessment and the results of these markers may lead to a reduction in the cardiac event rate