Table 2.

Current diagnostic methods for patients with suspected CAD.

Modality	Mechanism interpretation	Strengths	Limitations	Performance		Considerations	Recommendations
				Sensitivity	Specificity
Functional testing
Stress ECG	Continuous 12-lead ECG acquired during exercise (treadmill or stationary bike) Abnormal: >1 mm ST depression in two contiguous leads, arrhythmia, below-average exercise capacity High risk: Duke treadmill score <–11 or abnormal haemodynamic response	Noninvasive Low cost, quick Functional capacity assessed Widely available – often can be done at point of care or in the office/clinic	Suboptimal sensitivity Does not localize ischemia Low detection rate of single-vessel disease Operator and patient dependence (wide range of sensitivity/specificity performance estimates)	54 (51–66%)	58 (51–69%)	LBBB, ST depression > 1mm, pre-excitation, paced rhythm Digoxin use Not appropriate for patients who cannot exercise (claudication, deconditioning, arthritis, pulmonary disease) Particularly poor performance in premenopausal women	No longer solely recommended for evaluation of de novo CAD diagnosis Can be used to risk stratify (i.e. for discharge) while awaiting a higher fidelity test.
Stress Echo	Echocardiography with exercise or pharmacologically induced stress Ventricular size, wall motion and function (± valves) can be assessed Abnormal: new wall motional abnormalities or abnormal LVEF with stress	Noninvasive No radiation Simultaneous structural information, localization of ischaemia Improved sensitivity and specificity compared to ECG alone	Reduced performance in those with poor imaging windows Operator dependent Largely qualitative analysis Low(er) sensitivity for single-vessel disease	76 (72–79)%	80 (71–88)%	Poor imaging windows – morbid obesity, severe COPD, chest wall deformity. Now somewhat offset with contrast. Baseline regional wall motion abnormalities can complicate assessment	Provides a coarse assessment of cardiac structure/function on baseline imaging
SPECT	Radionuclide (technetium, sestamibi, thallium, tetrofosmin) perfusion imaging using either vasodilator or chronotropic stress. Based on coronary ‘steal’ phenomenon. Coarse LV function assessment Abnormal: perfusion defect or coarse wall motion abnormality	Perfusion evaluation (relative) Quantitative assessment possible Similar performance for exercise and pharmacological stimuli	Radiation exposure (12–37 mSv) ‘Balanced ischaemia’ may lead to false negatives	81 (74–86)%	78 (70–85)%	Soft tissue attenuation: poorer images from obesity, breast artefacts, and liver artefacts Radiation implications for obese (higher dose) and women (breast tissue) Potentially less sensitive in ESRF	Ideal in patients with poor echo windows or unable to exercise
Stress PET	PET under pharmacological stress Abnormal: perfusion defect	Absolute quantitation of perfusion defect possible Higher image quality than SPECT	Less available Pharmacological only High cost Radiation exposure (10–14 mSv)	85 (71–99%)	86% (65–97)	Limited availability/expensive	Women (less radiation, less breast attenuation) Obesity
Stress CMR	Magnetic resonance imaging of myocardium under pharmacological stress (perfusion using adenosine or regional wall motion using dobutamine) Abnormal: perfusion abnormalities with vasodilator; WMA with dobutamine	High resolution Subendocardial perfusion and viability can be assessed No radiation Structural evaluation Can also evaluate viability Qualitative and semi-quantitative analysis possible	Less available High cost Claustrophobia can be limiting Unable to give gadolinium with GFR < 30ml/min/m2	84 (76–90)%	85 (77–90)%	Absolute: metallic foreign bodies. CMR-safe devices now mainstream but old ICDs are unsafe Significantly obese patients may not fit in scanner
Anatomical testing
CACS	Score calculated based on volume and density of calcification (Agatston score) Abnormal: >100 and >400 are traditional cut points although linear association with risk. Zero provides an excellent prognosis	Quick, easy Widely available No contrast	Very modest radiation dose Does not provide information on stenosis	58 (46–69)%	62 (54–69)%	Historically used for risk stratification rather than ‘diagnosis’ per se	Has been studied with functional testing to provide a combined assessment May be considered in low pre-test probability patients
CCTA	Structural luminal narrowing quantified. Abnormal: luminal irregularities or narrowing; >50% considered positive	Noninvasive Detects obstructive CAD (versus CAC) Quick structural assessment Can assess CT-FFR	Does not confirm ischaemia Motion artefacts high Calcification causes bloom artefacts, limiting lumen assessment Time-intensive interpretation and image construction Radiation exposure (1–5 mSv)	96 (94–97)%	79 (72–84)%	CKD and contrast Radiation implications for obese (higher dose) and women (breast tissue) Image quality less robust with AF or high heart rates Distal vessels sometimes not well seen	Rule-out test in patients with low likelihood – very high negative predictive value. Could be considered in ‘triple rule out’ for CAD, PE and aortic dissection
ICA	High-resolution assessment of coronary lumen Gold standard	Able to proceed with revascularization at the same sitting Can be paired with invasive functional assessment to have combined evaluation (FFR, iFR)	Does not confirm ischaemia or degree of luminal narrowing Radiation exposure Invasive Resource intensive Associated with risk: 1 in 1000 of MI, stroke or death	100%	100%	CKD and contrast	Refractory or progressive symptoms High chance of needing revascularization

AF, atrial fibrillation; CACS, coronary artery calcium score; CAD, coronary artery disease; CCTA, coronary CT angiography; CKD, chronic kidney disease; CMR, cardiac magnetic resonance; COPD, chronic obstructive pulmonary disease; CT-FFR, CT fractional flow reserve; ECG, electrocardiography; ESRF, end-stage renal failure; FFR, fractional flow reserve; iFR, instantaneous flow reserve; ICA, invasive coronary angiography; ICD, implantable cardiac defibrillator; LBBB, left bundle branch block; LV, left ventricle; LVEF, left ventricular ejection fraction; MI, myocardial infarction; PE, pulmonary embolism; PET, positron emission tomography; SPECT, single photon emission computed tomography.^27–30