Clinical Correlation
Prediction of disease is one of the primary functions of stress testing. We would like to be able to predict in each patient.
1) The anatomical condition of the coronary arteries.
2) The functional status of the heart.
3) The ultimate outcome of the patient as influenced by the above two parameters.
Corelation of ST Depressoin with Coronary Angiography
Various investigators considered 1 mm of horizontal or downsloping ST depression to denote a positive test and used from 50-75 per cent cross sectional narrowing as a significant coronary lesion. From the data available at this time the following statements regarding average correlations between catheterization data and maximal stress testing seem in order if ST-segments are taken as the only marker for coronary ischaemia.
1) Men with single vessel disease and significant coronary narrowing of 70 per cent of luminal diameter have about 50 to 60 per cent chance of an abnormal test result.
2) Men with two-vessel disease have a 65 per cent chance of an abnormal test result.
3) Men with three-vessel disease have a 78 per cent chance of an abnormal test result.
4) Men with left main disease have an 85 per cent chance of an abnormal test result.
5) Men admitted for evaluation of chest pain who are over age 45 with 1.0 mm ST-segment depression have a 90 per cent chance of having coronary disease or evidence of significant left ventricular dysfunction.
6) Men in the above category with 1.5 mm of ST depression have a 94 to 95 per cent chance of having coronary disease or evidence of significant left ventricular dysfunction.
7) Men over age 45 with 2.0 mm or more ST-segment depression have a 98 per cent chance of having coronary disease or evidence of significant left ventricular dysfunction.
Silent Myocardial Ischaemia
This deals primarily with those who have never had symptoms recognized as being of cardiac origin. Others, who have had recognized myocardial infection but have been asymptomatic following this event, are commonly believed to be free of ischaemia but limited somewhat by scar tissue replacing function myocardium. In actuality, more than 50 per cent of this group have other vessels significantly narrowed. Although many subjects with silent CAD have a sudden coronary event, the risk of an event is probably less than if ischaemia is associated with typical anginal pain. The risk of an event with asymptomatic ischaemia is about 50 per cent of that when classical angina accompanies the ECG findings during stress testing. When subjects with silent ischaemia are followed up for 5 years, those who convert to classic angina, have a poorer prognosis than those who remain asymptomatic. Even though the patient may come in with no history of chest pain, any type of chest discomfort, upper abdominal gas or bloating, inordinate dysponea with exercise or just increasing fatigue, may be an angina equivalent.
False Positive Tests
As ST depression has been equated with CAD, patients with this finding who have less than a critical coronary narrowing has been called false positives. Upon careful scrutiny of these patients, however most are found to have some process or condition that could explain the repolarization abnormality. In a study of 95 patients with ST-segment depression and normal coronary arteries, it was found that only 13 per cent did not have any possible explanation.Eriksson and Mybre followed up 36 men for 7 years with normal coronary arteries and ST depression. The incidence of cardiac events after seven years was the same in this group as in those who were found to have significant CAD. The investigators believe that many of these patients represent early myocardiopathies and that the ST-segment was due to abnormalities in the vasodilator reserve. It is now known that coronary atheromas that do not appear to be flow limiting may cause decreased perfusion and ischaemia. Thus, the term false positive ST depression should probably be abandoned and replaced with abnormal ST depression of unknown cause.
Prediction of disease is one of the primary functions of stress testing. We would like to be able to predict in each patient.
1) The anatomical condition of the coronary arteries.
2) The functional status of the heart.
3) The ultimate outcome of the patient as influenced by the above two parameters.
Corelation of ST Depressoin with Coronary Angiography
Various investigators considered 1 mm of horizontal or downsloping ST depression to denote a positive test and used from 50-75 per cent cross sectional narrowing as a significant coronary lesion. From the data available at this time the following statements regarding average correlations between catheterization data and maximal stress testing seem in order if ST-segments are taken as the only marker for coronary ischaemia.
1) Men with single vessel disease and significant coronary narrowing of 70 per cent of luminal diameter have about 50 to 60 per cent chance of an abnormal test result.
2) Men with two-vessel disease have a 65 per cent chance of an abnormal test result.
3) Men with three-vessel disease have a 78 per cent chance of an abnormal test result.
4) Men with left main disease have an 85 per cent chance of an abnormal test result.
5) Men admitted for evaluation of chest pain who are over age 45 with 1.0 mm ST-segment depression have a 90 per cent chance of having coronary disease or evidence of significant left ventricular dysfunction.
6) Men in the above category with 1.5 mm of ST depression have a 94 to 95 per cent chance of having coronary disease or evidence of significant left ventricular dysfunction.
7) Men over age 45 with 2.0 mm or more ST-segment depression have a 98 per cent chance of having coronary disease or evidence of significant left ventricular dysfunction.
Silent Myocardial Ischaemia
This deals primarily with those who have never had symptoms recognized as being of cardiac origin. Others, who have had recognized myocardial infection but have been asymptomatic following this event, are commonly believed to be free of ischaemia but limited somewhat by scar tissue replacing function myocardium. In actuality, more than 50 per cent of this group have other vessels significantly narrowed. Although many subjects with silent CAD have a sudden coronary event, the risk of an event is probably less than if ischaemia is associated with typical anginal pain. The risk of an event with asymptomatic ischaemia is about 50 per cent of that when classical angina accompanies the ECG findings during stress testing. When subjects with silent ischaemia are followed up for 5 years, those who convert to classic angina, have a poorer prognosis than those who remain asymptomatic. Even though the patient may come in with no history of chest pain, any type of chest discomfort, upper abdominal gas or bloating, inordinate dysponea with exercise or just increasing fatigue, may be an angina equivalent.
False Positive Tests
As ST depression has been equated with CAD, patients with this finding who have less than a critical coronary narrowing has been called false positives. Upon careful scrutiny of these patients, however most are found to have some process or condition that could explain the repolarization abnormality. In a study of 95 patients with ST-segment depression and normal coronary arteries, it was found that only 13 per cent did not have any possible explanation.Eriksson and Mybre followed up 36 men for 7 years with normal coronary arteries and ST depression. The incidence of cardiac events after seven years was the same in this group as in those who were found to have significant CAD. The investigators believe that many of these patients represent early myocardiopathies and that the ST-segment was due to abnormalities in the vasodilator reserve. It is now known that coronary atheromas that do not appear to be flow limiting may cause decreased perfusion and ischaemia. Thus, the term false positive ST depression should probably be abandoned and replaced with abnormal ST depression of unknown cause.
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| Terms used in exercise stress testing |
False Negaive Tests
When patients are found to have significant coronary narrowing and fail to have exercise induced ST depression, they have been labeled false negative. This can be understood when the obstructed artery subtends an area of scar, suggesting that there is no ischaemic muscle to produce the characteristic ECG changes. Indeed, the prevalence of an ischaemic ST response is reduced in subjects with a previous infarction, especially if it is a large anterior wall scar.Sensitivity = Per cent of all patients with disease who manifest an abnormal test
((true positive)/(true positive + false negative))x 100
Specificity = per cent of all patient without disease who manifest a negative test
((true negetive)/(true negetive + false positive))x 100
Specificity = per cent of positive tests that are truly positive
((true positive)/(true positive + false positive))x 100
The open area of the diagram represents patients with coronary artery disease who undergo an exercise stress test and the shaded portion represents patients without coronary disease who perform a stress test.
Harder to understand is that patient who has no known previous infarction but has classic angina on exercising with no detectable ST change. This has been observed even in patients with left main coronary disease. Weiner and colleagues analyzed the false negative tests from the case study and reported that they were as common in patients with multivessel disease as in those with single vessel disease. They found that even in patients with three-vessel disease, the absence of ST depression (horizontal or downsloping) predicted a very low probability of a coronary event in 4 years. Weiner and colleagues also claim that the achieved heart rate response had no effect on the likelihood of a false negative. In some patients, the magnitude of ischaemia is probably inadequate to produce a significant current of injury, in others; the ischaemia may be in both the anterior and posterior wall so that the ST changes cancel each other out.
Because ST depression is due to subendocardial ischaemia with the attendant potassium shift,factors that would alter this process may come into play. Probably the most common factor, in patients with severe three vessel disease, is patchy scarring of the subendocardium, often unrecognized in the resting ECG. Low voltage can also be a factor.
Stress Testing in Women
Data on mortality in men is about 2.5 times that of women. At younger ages, however, CAD in men exceeds that found in women by 5 to 1. It is found that risk factors of smoking and use of oral contraceptives are almost always present when CAD is found in premenopausal non diabetic women. It is paradoxical that exercise induced ST depression in normal women younger that 45 years, has been found to be much more common than in men (almost four times). Because CAD is known to be less prevalent in women than in men, these changes must be presumed to be due to some process independent of coronary atherosclerosis.
Mechanisms
Estrogen has been implicated as a cause of ST depression. For years it seemed that estrogen protect women from coronary artery disease. Also several reports tend to strongly link the hormone with exercise induced ST depression.When testing women, the pretest likelihood cannot be ignored. Careful attention to the history of pain, medications, physical signs, and other lab signs of disease will go a long way toward helping to distinguish the true disease process. Mitral prolapse is often associated with ST depression in young pre menopausal women.
Rapid upsloping ST, increasing septal Q amplitude, and large P-waves suggesting the possibility of a large Ta wave can also alert us to the probability of a false positive test. If indicated thallium stress testing performed in high quality laboratories may add data to confirm or negate the results suggested by ST-segment depression after the standard exercise test has been completed. The ST/HR slope holds the most promise for a highly accurate exercise test in women. Angiography is indicated in certain clinical situations even when normal coronary arteries are suspected.
Conclusions
It appears that even using careful clinical analysis and all the information available during stress testing, the reliability of the stress test in women is lower than that of men. It is important to remember that the prevalence of false positive ST depression is high in younger women, who are unlikely to have CAD on the basis of age alone. As they age, the number of false positive changes decreases and ST depression becomes a more reliable marked for CAD. Even though there are more false positive tests in women a negative test provides a greater assurance that there is no disease than a negative test in men.
Stress Testing after Myocardial Infraction
Many post infarction deaths are sudden and occur with in the first 6 months after infarction.Exercise testing from 10 days to weeks after an MI is an efficient and established way to detect those at high risk. Although the risks of doing exercise testing have probably been underreported,at this point it seems reasonably safe. The post MI stress test, then, emerged to provide us with a means of selecting patients at high risk among those who are asymptomatic and have uncomplicated convalescence, permitting the implementation of aggressive management that might reduce mortality and morbidity. Stratification of patients soon after an MI with exercise stress testing offers several other benefits. Exercise testing defines the patients functional cardiac capacity by which activity level and rehabilitation can be rationally prescribed. It provides a safe basis to advised patients regarding return to normal activities and work. The major determinant of risk is probably patient selection.
When patients are found to have significant coronary narrowing and fail to have exercise induced ST depression, they have been labeled false negative. This can be understood when the obstructed artery subtends an area of scar, suggesting that there is no ischaemic muscle to produce the characteristic ECG changes. Indeed, the prevalence of an ischaemic ST response is reduced in subjects with a previous infarction, especially if it is a large anterior wall scar.Sensitivity = Per cent of all patients with disease who manifest an abnormal test
((true positive)/(true positive + false negative))x 100
Specificity = per cent of all patient without disease who manifest a negative test
((true negetive)/(true negetive + false positive))x 100
Specificity = per cent of positive tests that are truly positive
((true positive)/(true positive + false positive))x 100
The open area of the diagram represents patients with coronary artery disease who undergo an exercise stress test and the shaded portion represents patients without coronary disease who perform a stress test.
Harder to understand is that patient who has no known previous infarction but has classic angina on exercising with no detectable ST change. This has been observed even in patients with left main coronary disease. Weiner and colleagues analyzed the false negative tests from the case study and reported that they were as common in patients with multivessel disease as in those with single vessel disease. They found that even in patients with three-vessel disease, the absence of ST depression (horizontal or downsloping) predicted a very low probability of a coronary event in 4 years. Weiner and colleagues also claim that the achieved heart rate response had no effect on the likelihood of a false negative. In some patients, the magnitude of ischaemia is probably inadequate to produce a significant current of injury, in others; the ischaemia may be in both the anterior and posterior wall so that the ST changes cancel each other out.
Because ST depression is due to subendocardial ischaemia with the attendant potassium shift,factors that would alter this process may come into play. Probably the most common factor, in patients with severe three vessel disease, is patchy scarring of the subendocardium, often unrecognized in the resting ECG. Low voltage can also be a factor.
Stress Testing in Women
Data on mortality in men is about 2.5 times that of women. At younger ages, however, CAD in men exceeds that found in women by 5 to 1. It is found that risk factors of smoking and use of oral contraceptives are almost always present when CAD is found in premenopausal non diabetic women. It is paradoxical that exercise induced ST depression in normal women younger that 45 years, has been found to be much more common than in men (almost four times). Because CAD is known to be less prevalent in women than in men, these changes must be presumed to be due to some process independent of coronary atherosclerosis.
Mechanisms
Estrogen has been implicated as a cause of ST depression. For years it seemed that estrogen protect women from coronary artery disease. Also several reports tend to strongly link the hormone with exercise induced ST depression.When testing women, the pretest likelihood cannot be ignored. Careful attention to the history of pain, medications, physical signs, and other lab signs of disease will go a long way toward helping to distinguish the true disease process. Mitral prolapse is often associated with ST depression in young pre menopausal women.
Rapid upsloping ST, increasing septal Q amplitude, and large P-waves suggesting the possibility of a large Ta wave can also alert us to the probability of a false positive test. If indicated thallium stress testing performed in high quality laboratories may add data to confirm or negate the results suggested by ST-segment depression after the standard exercise test has been completed. The ST/HR slope holds the most promise for a highly accurate exercise test in women. Angiography is indicated in certain clinical situations even when normal coronary arteries are suspected.
Conclusions
It appears that even using careful clinical analysis and all the information available during stress testing, the reliability of the stress test in women is lower than that of men. It is important to remember that the prevalence of false positive ST depression is high in younger women, who are unlikely to have CAD on the basis of age alone. As they age, the number of false positive changes decreases and ST depression becomes a more reliable marked for CAD. Even though there are more false positive tests in women a negative test provides a greater assurance that there is no disease than a negative test in men.
Stress Testing after Myocardial Infraction
Many post infarction deaths are sudden and occur with in the first 6 months after infarction.Exercise testing from 10 days to weeks after an MI is an efficient and established way to detect those at high risk. Although the risks of doing exercise testing have probably been underreported,at this point it seems reasonably safe. The post MI stress test, then, emerged to provide us with a means of selecting patients at high risk among those who are asymptomatic and have uncomplicated convalescence, permitting the implementation of aggressive management that might reduce mortality and morbidity. Stratification of patients soon after an MI with exercise stress testing offers several other benefits. Exercise testing defines the patients functional cardiac capacity by which activity level and rehabilitation can be rationally prescribed. It provides a safe basis to advised patients regarding return to normal activities and work. The major determinant of risk is probably patient selection.
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| Value of Stress Testing in Evaluating Inducible Ischaemia after revascularisation |
Protocols
Most early treadmill stress tests are performed either at discharge or within two weeks of an MI ard terminated with the attainment of a specific heart rate, usually 70 per cent of the maximum predicted heart rate for age (normal 120 to 130 bpm) or when a workload of 3 to 5 METS has been achieved. Modified heart rate or workload limited tests are referred to as sub-maximal treadmill stress test. Some studies however, use symptom limited or sign limited tests using greater workloads. DeBosk and Haskell, compared symptom limited and heart rate limited modified treadmill protocol at three weeks after on MI and found both equally safe and effective in provoking ischaemia, abnormalities and identifying patients at risk of subsequent coronary events.
ST Segment Depression
The development of ST-segment depression with exercise is probably the most reliable sign if myocardial ischaemia and appears to be the most useful parameter of prognostic importance. The reported incidence varies from 15 to 40 per cent. It is found that exercise induced ST depression of 1 mm or greater on a submaximal treadmill protocol was highly predictive of subsequent mortality during a one year period. The risk of a cardiac event doubles between ST-segment depression of 1 to 2 mm and ST-segment depression of 2 mm or greater.
Exercise – Induced Ventricular Arrhythmias
The prognostic significance of ventricular ectopy provoked by stress testing after an MI is controversial. Complex ventricular arrhythmias detected by ambulatory ECG monitoring during the late hospital phase of an infarction have been reported to adversely affect prognosis. The reported incidence of post MI exercise induced ventricular arrhythmias range from 20 per cent to 60 per cent.
Hemodynamic Responses
Reduced exercise capacity roughly reflects impaired LV function, and may contribute its prognostic value to this association. Completing a workload of at least 3 MET implies a favorable prognosis even if ST-segment depression or ventricular arrhythmias occurred. Excluding patients with clinical heart failure, it is found that a maximum workload of less then 4 METS at 3 weeks after infarction, is a risk factor for future cardiac events. Inadequate blood pressure response (defined as an increase of 10mm or less in systolic blood pressure with a peak systolic blood pressure of 140mm or less, or a fall of greater than 20mm in systolic pressure from peak systolic blood pressure) also appeared predictive of coronary events and seemed to correlate with exercise duration.
ST-Segment Elevation
Exercise induced ST-segment elevation is common in subjects with post MI stress tests in leads where Q-waves are present. It has been correlated with abnormal wall motion in the area of infarction. However, approximately 50 per cent of the ST-segment elevation observed initially with pre discharge stress tests will be absent on retesting at 6 weeks, which may reflect improvement of abnormal wall motion with fibrosis and scarring or it may be due to recovery of hibernating myocardium. It rarely occurs with inferior infarction, and the ejection fraction is significantly lower in patients demonstrating ST-segment elevation. Thus, when the ST-segment elevation is noted on post MI stress testing that becomes more marked with exercise it may indicate viable myocardium in the region of the infarct.
Findings Predictive of Future Events
1) ST-segment depression.
2) Short exercise duration.
3) High heart rate at low workload.
4) Failure to increase blood pressure or fall below control.
5) Complex premature ventricular ectopy, with poor left ventricular function.
Most early treadmill stress tests are performed either at discharge or within two weeks of an MI ard terminated with the attainment of a specific heart rate, usually 70 per cent of the maximum predicted heart rate for age (normal 120 to 130 bpm) or when a workload of 3 to 5 METS has been achieved. Modified heart rate or workload limited tests are referred to as sub-maximal treadmill stress test. Some studies however, use symptom limited or sign limited tests using greater workloads. DeBosk and Haskell, compared symptom limited and heart rate limited modified treadmill protocol at three weeks after on MI and found both equally safe and effective in provoking ischaemia, abnormalities and identifying patients at risk of subsequent coronary events.
ST Segment Depression
The development of ST-segment depression with exercise is probably the most reliable sign if myocardial ischaemia and appears to be the most useful parameter of prognostic importance. The reported incidence varies from 15 to 40 per cent. It is found that exercise induced ST depression of 1 mm or greater on a submaximal treadmill protocol was highly predictive of subsequent mortality during a one year period. The risk of a cardiac event doubles between ST-segment depression of 1 to 2 mm and ST-segment depression of 2 mm or greater.
Exercise – Induced Ventricular Arrhythmias
The prognostic significance of ventricular ectopy provoked by stress testing after an MI is controversial. Complex ventricular arrhythmias detected by ambulatory ECG monitoring during the late hospital phase of an infarction have been reported to adversely affect prognosis. The reported incidence of post MI exercise induced ventricular arrhythmias range from 20 per cent to 60 per cent.
Hemodynamic Responses
Reduced exercise capacity roughly reflects impaired LV function, and may contribute its prognostic value to this association. Completing a workload of at least 3 MET implies a favorable prognosis even if ST-segment depression or ventricular arrhythmias occurred. Excluding patients with clinical heart failure, it is found that a maximum workload of less then 4 METS at 3 weeks after infarction, is a risk factor for future cardiac events. Inadequate blood pressure response (defined as an increase of 10mm or less in systolic blood pressure with a peak systolic blood pressure of 140mm or less, or a fall of greater than 20mm in systolic pressure from peak systolic blood pressure) also appeared predictive of coronary events and seemed to correlate with exercise duration.
ST-Segment Elevation
Exercise induced ST-segment elevation is common in subjects with post MI stress tests in leads where Q-waves are present. It has been correlated with abnormal wall motion in the area of infarction. However, approximately 50 per cent of the ST-segment elevation observed initially with pre discharge stress tests will be absent on retesting at 6 weeks, which may reflect improvement of abnormal wall motion with fibrosis and scarring or it may be due to recovery of hibernating myocardium. It rarely occurs with inferior infarction, and the ejection fraction is significantly lower in patients demonstrating ST-segment elevation. Thus, when the ST-segment elevation is noted on post MI stress testing that becomes more marked with exercise it may indicate viable myocardium in the region of the infarct.
Findings Predictive of Future Events
1) ST-segment depression.
2) Short exercise duration.
3) High heart rate at low workload.
4) Failure to increase blood pressure or fall below control.
5) Complex premature ventricular ectopy, with poor left ventricular function.
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