What is the recommended workup for a patient suspected of having Coronary Artery Disease (CAD)?

CAD Workup: Diagnostic Algorithm

For patients with suspected coronary artery disease, begin with clinical risk stratification using the Risk Factor-Weighted Clinical Likelihood model, followed by non-invasive testing with coronary CTA (preferred) or functional imaging based on pre-test probability, reserving invasive angiography for high-risk patients or those with non-diagnostic non-invasive tests. 1

Initial Mandatory Assessment

All patients require the following baseline evaluation:

• Detailed clinical history focusing on cardiovascular risk factors (smoking, hyperlipidemia, diabetes, hypertension, family history of premature CAD), symptom characteristics including onset, duration, type, location, triggers, relieving factors, and time of day 1

• Resting 12-lead ECG in all patients with chest pain (unless obvious non-cardiac cause identified), particularly during or immediately after suspected ischemic episodes 1

• Basic biochemistry panel including lipid profile with LDL-C, full blood count with hemoglobin, creatinine with estimated renal function, and glycemic status with HbA1c and/or fasting plasma glucose 1

• Thyroid function testing at least once in all patients with suspected chronic coronary syndrome 1

• Resting transthoracic echocardiography to measure LVEF and volumes, identify regional wall motion abnormalities, exclude alternative causes of angina (hypertrophy, cardiomyopathy, valve disease), assess right ventricular function, and evaluate diastolic function 1

• Chest X-ray for patients with atypical presentation, signs/symptoms of heart failure, or suspected pulmonary disease 1

Critical pitfall: If clinical or ECG assessment suggests acute coronary syndrome rather than chronic coronary syndrome, immediately refer to emergency department with repeated high-sensitivity troponin measurement to rule out acute myocardial injury 1

Risk Stratification Using Pre-Test Probability

Calculate pre-test likelihood using the Risk Factor-Weighted Clinical Likelihood model, which generates categories: very low (≤5%), low (>5-15%), moderate (>15-50%), high (>50-85%), or very high (>85%) 1, 2

Adjust this estimate using additional clinical data including peripheral artery examination, resting ECG findings, resting echocardiography results, and presence of vascular calcifications on prior imaging 1

Diagnostic Testing Algorithm Based on Pre-Test Probability

Very Low Likelihood (≤5%)

• Defer further diagnostic testing and manage clinically 2, 3

Low Likelihood (>5-15%)

• Consider coronary artery calcium score (CACS) to reclassify patients into lower versus intermediate-high risk 2, 3
• Exercise ECG may be used for assessment of exercise tolerance, symptoms, arrhythmias, blood pressure response, and event risk in selected patients 1
• Important caveat: Exercise ECG is NOT recommended for diagnostic purposes in patients with ≥0.1 mV ST-segment depression on resting ECG, left bundle branch block, or digitalis treatment 1

Moderate Likelihood (>15-50%)

• Coronary CTA is the preferred initial test with diagnostic sensitivity of 97% and specificity of 80%, superior to functional testing 1, 2, 4
• Alternative: Non-invasive functional imaging (stress myocardial perfusion imaging by SPECT/PET, or stress echocardiography/cardiac MRI) if CTA is contraindicated or unavailable 1

CTA contraindications include: extensive coronary calcification, irregular heart rate, significant obesity, inability to cooperate with breath-hold commands, or conditions making good image quality unlikely 1

High Likelihood (>50-85%)

• Stress imaging tests (SPECT, PET myocardial perfusion imaging) to diagnose and quantify myocardial ischemia/scar 2, 5
• Alternative: Invasive coronary angiography in patients with severe symptoms refractory to medical therapy, typical angina at low exercise level, or clinical evaluation indicating high event risk 1

Very High Likelihood (>85%)

• Invasive coronary angiography as initial test 2, 5

Functional Significance Assessment

When anatomic stenosis is identified (50-90% diameter), functional assessment is mandatory before revascularization:

• Fractional flow reserve (FFR) ≤0.80 or instantaneous wave-free ratio (iwFR/iFR) ≤0.89 defines functionally significant stenosis 1, 2
• Stenoses >90% diameter are considered anatomically significant without requiring functional testing 1, 2
• Functional imaging for myocardial ischemia is recommended if coronary CTA shows CAD of uncertain functional significance or is non-diagnostic 1

Comparative Diagnostic Performance

The evidence strongly favors anatomic over functional testing in intermediate-risk patients:

• Coronary CTA: Area under ROC curve 0.91, sensitivity 91%, specificity 92% 4
• Myocardial perfusion imaging: Area under ROC curve 0.74, sensitivity 74%, specificity 73% 4
• Wall motion imaging: Area under ROC curve 0.70, sensitivity 49%, specificity 92% 4

Key point: CTA is significantly more accurate than functional testing for detecting obstructive CAD (p<0.001) 4

Risk Stratification After Diagnosis

Once CAD is diagnosed, stratify risk based on:

• Clinical assessment and LVEF measurement (resting echocardiography mandatory) 1
• Extent and severity of ischemia on functional imaging OR anatomic disease burden on CTA 1, 2
• Results of invasive physiological assessment (FFR/iwFR) if ICA performed 1, 2

For symptomatic high-risk patients: ICA complemented by invasive physiological guidance (FFR) is recommended for cardiovascular risk stratification, particularly if symptoms inadequately respond to medical treatment and revascularization is considered 1

Important limitation: ICA is NOT recommended solely for risk stratification without therapeutic intent 1

Special Diagnostic Considerations

For vasospastic angina: ECG during angina, invasive angiography or coronary CTA, and intracoronary acetylcholine testing during invasive angiography to provoke vasospasm 2

For microvascular dysfunction: Invasive coronary functional testing using coronary flow reserve (CFR) and index of microvascular resistance (IMR) 2

Critical pitfall: Do NOT use ST-segment alterations during supraventricular tachyarrhythmias as evidence of obstructive CAD 1