In ambulatory patients with suspected angina, the clinical assessment embraces nearly all the prognostic information provided by the resting electrocardiogram (ECG) and exercise ECG. The limited incremental value of these widely applied non-invasive investigations extended across all thirds of risk, emphasising the importance of the clinical assessment and the need for more effective methods of risk stratification in this group of patients.
In patients with undifferentiated chest pain there is a gradient of coronary risk, greatest in those with a diagnosis of angina but extending to those with a diagnosis of non-cardiac chest pain.5
The importance of a careful history is widely acknowledged. Our patients with typical angina, similar to those reported in a previous study,31
were at higher risk of adverse outcomes than patients with atypical symptoms. Experience of non-invasive testing in patients with undifferentiated chest pain has increased in recent years, but uncertainty about its value for risk assessment remains.14
We found that a range of abnormalities in both the resting ECG and the exercise ECG were independently predictive of adverse events in ambulatory patients with chest pain of recent onset. It is salutary to note, however, that 47% of all events during follow-up occurred in patients with a negative exercise ECG result, emphasising the limitations of using ECGs for risk assessment, and reminding us that the demonstration of a test’s independent prognostic value does not imply clinical utility if it is not incremental to information obtained more simply from the history and examination. In this respect our findings were unequivocal, particularly for the resting ECG, which showed no incremental prognostic value above that of the clinical assessment. For the exercise ECGs, incremental prognostic value seemed somewhat greater as reflected in point estimates for the C statistic, which increased by 5.7% for the exercise ECG subset with summary results and by 5.1% for the exercise ECG subset with more detailed results. Increases were only marginally greater among patients with an intermediate probability of coronary artery disease, the group in which the exercise ECG is most useful for diagnostic purposes.32
How to interpret such changes in the C statistic has been debated.33
In clinical terms the incremental prognostic value was trivial (see table 5), with the indices that incorporated data from the exercise ECG proving no more effective than those of the basic clinical assessment in predicting adverse outcomes. Importantly, detailed analysis of variables in the exercise ECG performed little better than the summary assessment that is commonly used in clinical practice.
Previous studies of treadmill testing in chest pain clinic populations have been small and, although confirming feasibility and safety, have not been powered to test prognostic value.14
Before these studies, a study15
had developed a prognostic treadmill score in a group of patients referred for cardiac catheterisation, which has since been validated in outpatient populations.16
Both development and validation groups in these studies contrasted with our patients, however, being predominantly male, often with a history of myocardial infarction and other manifestations of bias from investigations owing to their selection from patients referred for cardiac catheterisation. Application of this score to patients with chest pain of recent onset in chest pain clinics therefore requires caution. Nevertheless, the incremental value of the score for predicting survival at four years in an outpatient population was modest and similar to our exercise ECG model.16
In another study the increment in the C statistic was similarly modest when the treadmill score was added to the clinical assessment model.18
More recently, prognostic scores by the ACTION trialists34
and Euro heart investigators35
have been presented, but these scores utilise data not always available at first presentation and apply to patients with chronic stable angina, many with a history of myocardial infarction and whose risk characteristics are different from the patients with suspected angina in the present study.
The methods in this study are robust and reflect the incremental value of the different statistical models rather than simple comparison of likelihood ratios. We excluded only 7% of patients (n=725) because of missing data or not being traced by central registries. This is unlikely to have affected our conclusions because outcomes in this group were not significantly different from those included in our study. Important limitations were the absence of data on lipid levels and family history, although had these been available they would probably have improved the discriminatory power of the clinical model and would not therefore have affected our conclusions. Similarly, our conclusions would not have been affected by exclusion of the 167 patients (2%) with Q waves, suggesting a history of silent infarction, because this would have further reduced the prognostic value of the resting ECG. An abnormal exercise ECG result influences decisions on revascularisation, which in turn might influence prognosis. A sensitivity analysis using coronary artery bypass grafting as part of the composite end point did not, however, change the findings. We did not capture the exact magnitude of change in the ST segment during the exercise test, but this is not a serious limitation for prognostic assessment. The presence of such change is indicative of ischaemia but may not correlate with coronary anatomy,36 37
and agreements on changes in the ST segment can vary between observers. One of the most consistent prognostic markers in exercise testing is maximum exercise capacity,32
the specific variable (maximum duration of exercise, level of metabolic equivalents achieved, maximum workload, maximum heart rate, double product) used to summarise this being less important. The prognostic importance of age is not undermined by its lack of significance in the final incremental model, which merely indicates that in patients undergoing exercise testing, more prognostic weight is contributed by exercise time, the presence of change in the ST segment, and typical chest pain.
In conclusion, our study emphasises the importance of the clinical assessment for prognosis in patients with suspected angina. The data show that the need to improve risk stratification cannot be met by the resting ECG whereas the incremental value of the exercise ECG is small. Alternative tests are needed but must be developed within cohorts from chest pain clinic because prognostic value depends on the population in which the test is applied.38
A prerequisite of any new test should be the demonstration of its incremental value over clinical assessment if risk stratification is to be improved and the potential for chest pain clinics to reduce coronary mortality is to be fully realised.
What is already known on this topic
- Accurate identification of patients with suspected angina at higher risk of acute coronary syndromes and death is essential to tailor management strategies
- Resting and exercise electrocardiography are the most widely performed non-invasive tests in patients with suspected angina but their contribution to risk assessment is unknown
- Most research has focused on newer and more costly tests for diagnosing coronary disease, with less attention to incremental value for risk assessment
What this study adds
- Clinical assessment of patients with suspected angina embraces most of the prognostic information provided by resting ECGs and by exercise ECGs
- The incremental prognostic value of detailed exercise ECG variables is little better than the summary assessment of ischaemia commonly used
- More effective methods of risk stratification in this group of patients are needed