Definition and clinical rationale
Stable angina, or chronic chest pain attributable to suspected chronic coronary syndrome, is evaluated by estimating the likelihood of obstructive coronary artery disease (CAD) before diagnostic testing. This pre-test probability is the clinician’s estimate of the probability that the patient has anatomically obstructive CAD before the result of a new test is known.
The pre-test probability is central because the clinical value of any diagnostic test depends not only on its sensitivity and specificity but also on disease prevalence in the population being tested. A negative result is most useful when the initial probability is sufficiently low that obstructive CAD can be safely excluded. Conversely, a positive result is most persuasive when the initial probability is high enough that the result meaningfully increases the likelihood of disease and can justify further investigation or treatment.
Testing is therefore not an automatic response to chest pain. It is appropriate when the expected information is likely to change management. In patients with a very low probability of obstructive CAD, testing may generate false-positive results and unnecessary downstream procedures. In patients with a high probability, testing may add little diagnostic value and invasive coronary angiography may be more appropriate when symptoms, risk or anatomical considerations warrant it.
The contemporary diagnostic strategy also recognises that symptoms of myocardial ischaemia may arise from obstructive atherosclerotic CAD, coronary microvascular dysfunction or vasospasm. A normal or non-obstructive coronary anatomy does not necessarily exclude an ischaemic mechanism.
Clinical assessment and estimation of pre-test probability
Symptoms and clinical context
The assessment begins with the clinical presentation, including the character and stability of chest discomfort, associated dyspnoea, and the presence of risk factors or previously identified coronary calcification. Age and sex remain important determinants of the expected prevalence of obstructive CAD, but symptom characteristics and clinical judgement must be incorporated.
In symptomatic individuals without known CAD, newer clinical prediction algorithms are preferred over older approaches based solely on age, sex and typicality of symptoms. These newer models improve identification of patients with very low likelihood of obstructive CAD and may reduce unnecessary diagnostic testing.
Coronary artery calcium (CAC) provides additional information. A quantitative CAC score from dedicated testing, or a qualitative assessment of CAC on a non-gated chest CT, can modify the estimated likelihood of atherosclerotic obstructive CAD. CAC is therefore not merely an incidental imaging finding; it can refine the decision to test and may identify patients who require preventive therapy even when functional testing is normal.
Probability categories
The source material describes several clinically useful probability thresholds:
Very low probability: less than 5% in the European guideline framework. Diagnostic testing should generally be deferred.
Low probability: up to 15% in the chest-pain pathway. Testing is optional and may be selected according to clinical judgement.
Low to moderate probability: greater than 5% to 50% in the chronic coronary syndrome pathway. Coronary CT angiography (CCTA) is generally preferred to exclude obstructive CAD.
Intermediate or high probability: above 15% in the chest-pain pathway. Either CCTA or functional imaging is appropriate.
Very high probability or high-risk clinical presentation: invasive coronary angiography may be appropriate, particularly when symptoms are severe, refractory to guideline-directed medical therapy, occur at a low level of exertion, or are associated with high event risk.
The apparent differences between thresholds reflect different guideline frameworks and clinical pathways rather than a single universal classification system. In practice, the probability estimate should be integrated with the patient’s symptoms, age, CAC, comorbidities, test feasibility, local expertise and the likelihood that the result will alter management.
Illustrative pre-test probabilities
The following values describe the upper ranges of estimated obstructive CAD probability according to age, sex and presentation in symptomatic patients. They are not a substitute for individual clinical assessment.
| Age (years) | Chest pain: men | Chest pain: women | Dyspnoea: men | Dyspnoea: women |
|---|---|---|---|---|
| 30–39 | ≤4% | ≤5% | 0% | 3% |
| 40–49 | ≤22% | ≤10% | 12% | 3% |
| 50–59 | ≤32% | ≤13% | 20% | 9% |
| 60–69 | ≤44% | ≤16% | 27% | 14% |
| ≥70 | ≤52% | ≤27% | 32% | 12% |
These estimates are modified by symptom quality and CAC. Patients with lower-risk symptoms than those represented in the table would be expected to have lower probabilities.
Choosing whether to test
Very low and low probability
When the probability of obstructive CAD is very low, further diagnostic testing can generally be avoided. This approach reduces the risk of false-positive findings and unnecessary invasive procedures.
For patients with low probability, testing is optional. Possible approaches include:
No testing, with attention to symptom control and preventive therapy.
CAC assessment to quantify calcified plaque burden.
Exercise ECG without imaging in selected patients, providing information on exercise capacity and inducible ischaemia.
Testing should be pursued only when the result is likely to affect clinical management. In asymptomatic patients, no testing is indicated in the pathway described.
Intermediate probability
Patients with an intermediate probability are the group in whom non-invasive testing often provides the greatest incremental value. The choice is principally between:
Anatomic testing with CCTA.
Functional imaging for inducible myocardial ischaemia.
In symptomatic patients with a pre-test likelihood above 5%, either CCTA or non-invasive functional imaging is recommended as the initial test. For low or moderate probability, particularly in the range above 5% to 50%, CCTA is preferred for excluding obstructive CAD and identifying non-obstructive plaque.
Functional imaging is preferred when the principal question is whether an anatomical lesion produces myocardial ischaemia, when myocardial viability must be assessed, or when the results will guide revascularization decisions.
High probability and high-risk features
In patients with a high likelihood of obstructive CAD, non-invasive testing may still be appropriate if it will clarify anatomy or functional significance. However, invasive coronary angiography should be considered when there is:
Very high pre- or post-test likelihood of disease.
Severe symptoms despite guideline-directed medical therapy.
Angina at a low level of exercise.
High estimated event risk.
High-risk findings on non-invasive imaging.
Invasive angiography is also recommended when non-invasive testing leaves the diagnosis uncertain and confirmation or exclusion of obstructive CAD is required. When angiography identifies an intermediate stenosis, invasive functional assessment with fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) is recommended before revascularization.
Selection of the initial non-invasive modality
The initial test should be selected according to:
Estimated pre-test probability.
Age.
Symptoms and the clinical question.
CAC burden.
Contraindications or limitations of the available tests.
Local expertise and availability.
Baseline use of preventive therapy.
Whether anatomical plaque burden or inducible ischaemia is the principal management target.
Coronary CT angiography
CCTA is particularly useful for:
Excluding obstructive CAD in low-to-moderate probability patients.
Detecting non-obstructive atherosclerotic plaque.
Modifying the estimated probability of disease.
Identifying patients who may benefit from intensification of preventive treatment.
CCTA may be especially attractive in younger patients, including those younger than 65 years, and in patients not receiving optimal preventive therapy, because demonstrating total plaque burden may prompt escalation of preventive measures.
CCTA is less accurate for assessing lesion severity in older adults because coronary calcification is more prevalent and may impair interpretation. In patients with a known intermediate stenosis in a proximal or mid-coronary segment on CCTA, CT-based FFR may be considered. In the chest-pain pathway, CT-based FFR is also considered for lesions with 40%–90% stenosis when functional significance remains uncertain.
CCTA is recommended when functional imaging is non-diagnostic. Conversely, functional imaging is recommended when CCTA shows CAD of uncertain functional significance or is itself non-diagnostic.
Functional imaging
Functional testing evaluates the physiological consequences of coronary disease rather than anatomy alone. Available modalities include:
Stress echocardiography.
Stress single-photon emission computed tomography (SPECT).
Stress positron emission tomography (PET).
Stress cardiac magnetic resonance (CMR).
Functional imaging is particularly useful when the aim is to:
Relate symptoms to myocardial ischaemia.
Estimate myocardial viability.
Determine whether a coronary stenosis is functionally important.
Guide revascularization decisions.
Stress testing may be more advantageous in older patients, including those aged 65 years or more, because the probability of obstructive disease and ischaemia is higher. If feasible, exercise stress testing is preferable to pharmacological stress testing because it provides information about functional capacity, haemodynamic response and exercise-induced arrhythmias. In older adults with limited exercise capacity, the protocol may need to begin at a lower intensity with smaller workload increments.
Pharmacological stress options include dobutamine stress echocardiography and vasodilator stress myocardial perfusion imaging using dipyridamole, adenosine or regadenoson with thallium-201 and/or technetium-99m.
Test performance
Reported sensitivities and specificities for selected non-invasive tests are shown below. These values should be interpreted in the context of pre-test probability and the clinical population in which the test is used.
| Test | Sensitivity (95% CI) | Specificity (95% CI) |
|---|---|---|
| Exercise ECG | 0.58 (0.45–0.69) | 0.62 (0.54–0.69) |
| Stress echocardiography | 0.85 (0.80–0.89) | 0.82 (0.72–0.89) |
| Stress myocardial perfusion imaging | 0.87 (0.83–0.90) | 0.70 (0.53–0.76) |
| PET | 0.83 (0.70–0.93) | 0.89 (0.86–0.91) |
| CMR | 0.88 (0.80–0.93) | 0.89 (0.85–0.93) |
| CCTA | 0.97 (0.93–0.99) | 0.78 (0.67–0.86) |
CCTA has a high sensitivity in the presented data, supporting its role in ruling out obstructive disease. Its lower specificity relative to some functional modalities means that positive or equivocal anatomical findings may require functional clarification.
Exercise ECG has lower diagnostic sensitivity and specificity than the imaging-based techniques listed. It may nevertheless remain useful in selected low-risk patients, particularly when exercise capacity and haemodynamic response are clinically informative.
Role of coronary artery calcium
CAC can be obtained as a dedicated quantitative score or assessed qualitatively on a non-gated chest CT. It can be used to refine the pre-test likelihood of obstructive CAD and to identify the burden of calcified coronary plaque.
In low-risk symptomatic patients, CAC is an alternative to immediate diagnostic testing. In intermediate- or high-risk patients undergoing stress testing, adding CAC may provide useful information about plaque burden, because a normal stress study does not necessarily imply absence of coronary atherosclerosis.
The chest-pain pathway uses the following CAC categories to modify probability:
CAC 1–99.
CAC 100–999.
CAC ≥1,000.
The source material does not provide a complete numerical conversion from each CAC category to an individual post-test probability. The important clinical principle is that CAC can shift the estimated likelihood of atherosclerotic obstructive disease and inform preventive treatment even when functional testing does not demonstrate ischaemia.
Sequential and second-line testing
A second non-invasive test may be appropriate when the first test does not resolve the clinical question.
The principal sequences are:
Abnormal or equivocal CCTA: functional imaging to determine the physiological significance of CAD.
Abnormal or non-diagnostic functional testing: CCTA to define coronary anatomy.
CCTA showing 40%–90% stenosis: CT-based FFR or stress testing may be considered.
CCTA showing CAD of uncertain functional significance: functional imaging is recommended.
Non-invasive testing with an uncertain diagnosis: invasive coronary angiography with invasive functional assessment is recommended when confirmation or exclusion of obstructive CAD is required.
Selective second-line imaging can improve the selection of patients referred for invasive coronary angiography.
Invasive coronary angiography
Invasive coronary angiography is selected according to the clinical presentation, estimated probability of CAD, electrocardiographic findings, echocardiographic results, blood tests, stress-test findings and prior CT or magnetic resonance angiography.
It is recommended when:
Non-invasive testing leaves the diagnosis uncertain.
The pre-test or post-test likelihood of obstructive CAD is very high.
Symptoms are severe despite guideline-directed therapy.
Angina occurs with a low level of exertion.
The patient has high event risk.
Non-invasive testing demonstrates high-risk CAD or moderate-to-severe ischaemia.
When invasive angiography is performed, intermediate lesions should undergo physiological assessment with FFR or iFR before revascularization. Computed FFR derived from three-dimensional angiographic reconstruction is an emerging alternative to wire-based pressure assessment.
Exercise ECG and imaging findings
Exercise ECG
Exercise ECG may be used selectively in low-risk patients or when information about exercise capacity and exercise-induced ischaemia is desired. Its diagnostic performance is lower than that of the imaging-based tests listed above.
In an older patient with suspected high-risk disease, an exercise study may reveal several concerning features, including exercise-limiting chest pain, a fall in blood pressure and marked downsloping ST-segment depression. The source material describes such findings in association with extensive reversible perfusion abnormalities and high-risk angiographic CAD.
Myocardial perfusion imaging
SPECT and PET perfusion imaging may demonstrate reversible perfusion defects, indicating inducible ischaemia. High-risk findings described in the source material include:
Large or severe reversible perfusion defects.
Transient LV dilatation with stress.
A reduction in LV ejection fraction after exercise.
Extensive abnormalities involving multiple LV territories.
Visual perfusion assessment may underestimate the extent of multivessel disease because it can preferentially identify the territory supplied by the vessel with the most severe stenosis. Quantitative myocardial blood flow and myocardial flow reserve (MFR) can reveal more extensive impairment than visual imaging alone.
PET myocardial blood flow and flow reserve
PET permits routine quantification of myocardial blood flow and MFR. These measurements improve the sensitivity and negative predictive value of PET for excluding high-risk angiographic CAD. The source material reports that an MFR greater than 2.0 is associated with a negative predictive value greater than 97% for ruling out high-risk angiographic disease.
Reduced flow reserve may reflect diffuse or multivessel coronary disease even when visual perfusion imaging appears to show only a single-vessel defect. PET is preferred for absolute myocardial blood-flow measurement, although CMR perfusion may provide an alternative.
Preoperative testing
Routine non-invasive cardiac testing before major non-cardiac surgery is not supported for all patients. Testing should be considered in patients with poor or unknown functional capacity only when the result would alter clinical management or perioperative care.
The purpose of preoperative evaluation is primarily to identify clinical instability and determine suitability for surgery. Patients with acute CAD manifestations, unstable angina or decompensated heart failure require further evaluation and medical stabilisation before surgery.
Potential consequences of testing include:
Delay or cancellation of surgery.
Additional medical treatment.
Coronary investigation or intervention before surgery.
Higher-intensity monitoring or ICU care.
Modification of perioperative management.
The use of medications and interventions should reflect what would be implemented outside the surgical setting. The source material states that, except in the case of left main coronary artery stenosis, current data challenge the routine benefit of preoperative coronary revascularization solely to reduce surgical risk.
Special diagnostic pathway: ANOCA and INOCA
Patients may have anginal symptoms despite normal coronary arteries, non-obstructive lesions on non-invasive imaging, or intermediate stenoses with normal FFR or iFR. These patients may have angina with non-obstructive coronary arteries or ischaemia with non-obstructive coronary arteries.
In patients who remain persistently symptomatic despite medical therapy and have poor quality of life, invasive coronary functional testing is recommended to identify treatable endotypes. Testing with acetylcholine and adenosine can distinguish:
Endothelial dysfunction.
Impaired vasodilation, reflected by low coronary flow reserve and/or high microvascular resistance.
Epicardial vasospastic angina.
Microvascular vasospastic angina.
Combinations of these endotypes.
An equivocal response in which angina occurs without fulfilment of a defined endotype.
In suspected vasospastic angina, a 12-lead ECG should be recorded during an episode of angina. When recurrent rest angina is accompanied by transient ST-segment changes that resolve with nitrates and/or calcium antagonists, invasive functional angiography is recommended to confirm the diagnosis and assess the severity of underlying atherosclerotic disease.
For isolated vasospastic angina, calcium channel blockers are recommended to control symptoms, prevent ischaemia and reduce the risk of potentially fatal complications.
Decision-making in older adults
The decision to investigate an older adult should incorporate:
Pre-test likelihood of disease.
The probability that the result will change management.
Patient preferences and goals of care.
The risks and limitations of further testing.
The feasibility of exercise testing.
The likelihood that CAC will reduce the accuracy of CCTA because of extensive calcification.
A conservative approach is reasonable when the probability of high-risk disease is low, symptoms are mild or moderate and potentially controllable with medication, or the patient prefers to avoid further testing.
In patients with known chronic coronary disease, preserved or moderately reduced LV function and moderate-to-severe ischaemia, evidence supports either an initial conservative or invasive approach. An invasive strategy may provide greater improvement in angina-related quality of life in patients with more frequent baseline angina, whereas a conservative strategy avoids the early procedural risks associated with invasive treatment. These choices should be made through shared decision-making.
Guideline-based diagnostic pathway
A practical pathway for stable chest pain without known CAD is:
Assess symptoms and clinical risk
Very low probability
- Address preventive therapy and symptoms.
Low probability
- Consider CAC or exercise ECG in selected patients.
Intermediate or high probability
- Consider age, calcification, contraindications, local expertise and whether anatomy or ischaemia is the principal question.
CCTA showing no CAD or non-obstructive disease
- Consider an ANOCA/INOCA pathway when symptoms persist.
CCTA showing obstructive or potentially significant disease
- Refer for invasive angiography when high-risk anatomy, frequent angina, moderate-to-severe ischaemia or CT-based FFR ≤0.8 is present.
Abnormal or inconclusive functional testing
- Proceed to invasive angiography when the diagnosis remains uncertain or high-risk disease is suspected.
Invasive angiography
The initial non-invasive test should be selected according to pre-test probability, patient characteristics, local expertise and availability. For symptomatic individuals with a pre-test likelihood above 5%, either CCTA or functional imaging is recommended. CCTA is preferred for ruling out obstructive CAD in low- or moderate-probability patients, whereas functional imaging is preferred when the relationship between symptoms and ischaemia, myocardial viability or revascularization decisions is the primary concern.
Prognosis and follow-up
The source material does not provide a dedicated follow-up schedule for stable angina after non-invasive testing. It does, however, support reassessment according to persistence, worsening or increasing frequency of symptoms and the results of the initial evaluation.
Patients with no obstructive CAD or non-obstructive plaque should not necessarily be considered free of cardiovascular risk. Preventive therapy should be optimised according to the detected plaque burden and overall clinical assessment. Persistent or poorly controlled symptoms should prompt reconsideration of the diagnosis, review of the initial test and consideration of an ANOCA/INOCA pathway.
In patients with stable chronic coronary disease and moderate-to-severe ischaemia, an initial conservative strategy can be reasonable when LV function is preserved or only moderately impaired and there is no left main disease. Revascularization may nevertheless improve angina-related health status and reduce spontaneous myocardial infarction in selected patients, particularly when symptoms persist despite medical treatment.
The diagnostic process should therefore remain dynamic. The need for repeat or additional testing depends on symptom evolution, the initial test result, the possibility of high-risk CAD and whether further information is likely to change management.
