Ischemic Heart Disease (IHD) is the most common cardiovascular condition worldwide, and early detection of myocardial ischemia is critical to prevent progression to myocardial infarction or sudden cardiac death. Non-invasive diagnostic tools, particularly stress testing and imaging modalities, play a pivotal role in assessing coronary artery disease (CAD), identifying high-risk patients, and guiding therapeutic strategies.
The primary principle behind these tests is to evaluate the functional and structural consequences of impaired coronary perfusion. By increasing myocardial oxygen demand—through exercise or pharmacologic stressors—and simultaneously monitoring electrical, hemodynamic, or imaging parameters, clinicians can detect ischemia that may not be apparent at rest.
This article discusses the major non-invasive diagnostic modalities used in IHD: Exercise ECG (treadmill test), pharmacologic stress testing, echocardiography, myocardial perfusion imaging, and coronary CT angiography.
1. Exercise ECG (Treadmill Test)
1.1 Principles
The exercise ECG, also called the treadmill test (TMT), is one of the oldest and most widely used non-invasive methods for detecting myocardial ischemia. The test involves subjecting a patient to graded physical exercise (usually treadmill or bicycle ergometer) while continuously recording ECG, heart rate, blood pressure, and symptoms.
The rationale is that exercise increases myocardial oxygen demand; if coronary artery stenosis is present, supply cannot match demand, leading to ischemia. This ischemia is reflected as characteristic changes on ECG, usually ST-segment depression.
1.2 Indications
- Diagnosis of suspected CAD in patients with intermediate pre-test probability
- Risk stratification in patients with known CAD
- Assessment of exercise capacity and prognosis
- Post-myocardial infarction functional evaluation (in selected stable patients)
- Guiding cardiac rehabilitation and physical activity recommendations
1.3 Contraindications
Absolute contraindications:
- Acute myocardial infarction (within 2 days)
- Unstable angina
- Severe symptomatic aortic stenosis
- Decompensated heart failure
- Severe arrhythmias
- Acute pulmonary embolism or myocarditis
Relative contraindications:
- Left main coronary stenosis
- Moderate valvular heart disease
- Severe hypertension
- High-degree AV block
1.4 Protocol
- The Bruce protocol is most widely used: incremental increases in treadmill speed and incline every 3 minutes.
- Patient continues until:
- Target heart rate achieved (85% of age-predicted maximum)
- Limiting symptoms develop (angina, dyspnea, fatigue)
- Significant ECG changes appear
- Hypotension or dangerous arrhythmias occur
1.5 Diagnostic Criteria
- Positive test: Horizontal or downsloping ST-segment depression ≥1 mm at 80 ms after the J-point
- Other supportive findings: Development of angina, hypotension, ventricular arrhythmias, or failure of blood pressure to rise
1.6 Limitations
- Sensitivity: ~68%
- Specificity: ~77%
- False positives: Common in women, LV hypertrophy, digoxin therapy
- False negatives: May occur in mild CAD, single-vessel disease, or inadequate stress
1.7 Clinical Utility
- Best for patients who can exercise and have an interpretable baseline ECG
- Provides information about exercise tolerance, functional capacity, and prognosis
- Limited diagnostic accuracy compared to advanced imaging modalities
2. Pharmacologic Stress Testing
2.1 Principles
Some patients cannot perform adequate physical exercise due to orthopedic, neurological, or pulmonary limitations. In such cases, pharmacologic stress testing is used. Drugs are administered to simulate exercise effects on the heart—either by increasing myocardial oxygen demand or by vasodilating coronary arteries to reveal perfusion defects.
2.2 Types of Agents
- Vasodilators (adenosine, dipyridamole, regadenoson)
- Induce coronary vasodilation → stenosed vessels cannot dilate adequately → relative hypoperfusion revealed.
- Inotropes/chronotropes (dobutamine)
- Increase heart rate and contractility → mimic exercise demand.
2.3 Indications
- Patients unable to exercise adequately
- Poor baseline ECG (e.g., LBBB, paced rhythm, pre-excitation, ST abnormalities)
- Often combined with imaging (echo or nuclear perfusion)
2.4 Contraindications
- Severe asthma or bronchospasm (adenosine, dipyridamole)
- Hypotension, high-degree AV block (vasodilators)
- Severe hypertension, arrhythmias, obstructive hypertrophic cardiomyopathy (dobutamine)
2.5 Diagnostic Applications
- Always performed with imaging modality (echo or nuclear scan)
- Detects inducible ischemia in patients unsuitable for exercise ECG
- Higher sensitivity/specificity than treadmill ECG alone
3. Echocardiography in Stress Testing
3.1 Stress Echocardiography
Stress echocardiography combines exercise or pharmacologic stress with real-time echocardiographic imaging to detect ischemia.
Principle: Ischemia leads to regional wall motion abnormalities (RWMA) before ECG changes or angina appear.
3.2 Methods
- Exercise stress echo: Echocardiographic images obtained pre- and post-exercise.
- Dobutamine stress echo: Dobutamine infusion progressively increases HR and contractility.
- Contrast agents may be used to enhance endocardial border visualization.
3.3 Diagnostic Value
- Sensitivity: ~80–85%
- Specificity: ~80–90%
- Superior to exercise ECG in diagnostic accuracy
- Provides information on:
- Extent and severity of ischemia
- Viability of myocardium (distinguishing hibernating from scarred tissue)
- Left ventricular function
3.4 Indications
- Intermediate probability of CAD with inconclusive exercise ECG
- Assessment of myocardial viability before revascularization
- Prognostic evaluation after MI
- Evaluation of valvular heart disease under stress
3.5 Limitations
- Operator-dependent
- Limited acoustic windows in obese or COPD patients
- Requires experienced interpretation
4. Myocardial Perfusion Imaging (MPI)
4.1 Principles
Also known as nuclear stress test, MPI uses radioactive tracers (e.g., Technetium-99m, Thallium-201) and imaging with SPECT or PET scanners. It assesses myocardial blood flow at rest and during stress, identifying regions of ischemia or infarction.
4.2 Technique
- Patient undergoes exercise or pharmacologic stress.
- Radiotracer injected at peak stress → images acquired.
- Rest images taken later.
- Comparison of stress vs rest perfusion reveals ischemia.
4.3 Interpretation
- Reversible perfusion defect: Indicates ischemia
- Fixed perfusion defect: Indicates infarct/scar tissue
- Normal study: Uniform tracer uptake
4.4 Diagnostic Performance
- Sensitivity: ~87%
- Specificity: ~73%
- High negative predictive value (>95%) → excellent for ruling out CAD
4.5 Indications
- Suspected CAD with intermediate probability
- Risk stratification in known CAD
- Assessment of ischemic burden pre-revascularization
- Evaluation of myocardial viability
4.6 Advantages
- Quantifies extent and severity of ischemia
- Provides prognostic information
- PET offers higher spatial resolution and quantification of blood flow
4.7 Limitations
- Radiation exposure
- Time-consuming
- Limited availability in some regions
- Artifacts from soft tissue attenuation (e.g., breast, diaphragm)
5. Coronary CT Angiography (CCTA)
5.1 Principles
Coronary CT angiography (CCTA) uses advanced multidetector CT scanning with intravenous contrast to provide high-resolution images of coronary arteries. It directly visualizes atherosclerotic plaques and coronary lumen narrowing.
5.2 Diagnostic Role
- Excellent for ruling out CAD due to high negative predictive value
- Provides anatomical information on plaque burden, calcification, stenosis
- Can identify non-obstructive CAD not seen on stress testing
5.3 Indications
- Low-to-intermediate probability of CAD
- Atypical chest pain evaluation
- Inconclusive stress tests
- Assessment of coronary anatomy before non-coronary cardiac surgery
5.4 Advantages
- Non-invasive, rapid
- High sensitivity and specificity
- Detects both obstructive and non-obstructive plaque
- Provides additional information on extracardiac structures
5.5 Limitations
- Requires heart rate control (beta-blockers) for image quality
- Contraindicated in severe renal dysfunction (contrast) or allergy
- Radiation exposure, though decreasing with newer scanners
- Cannot provide functional assessment of ischemia (unless combined with CT perfusion or FFR-CT)
6. Comparative Summary of Non-Invasive Tests
| Test | Principle | Best Use Case | Sensitivity | Specificity | Limitations |
|---|---|---|---|---|---|
| Exercise ECG | ECG changes with exertion | Initial test in patients who can exercise, interpretable ECG | ~68% | ~77% | False positives, poor in women/LVH |
| Pharmacologic stress test | Drug-induced stress | Patients unable to exercise, poor baseline ECG | Varies with modality | Higher with imaging | Drug contraindications |
| Stress Echocardiography | Wall motion abnormalities | Ischemia detection, viability, prognosis | ~80–85% | ~80–90% | Operator dependent |
| Myocardial Perfusion Imaging (MPI) | Perfusion defects via SPECT/PET | Quantifying ischemia, viability, prognosis | ~87% | ~73% | Radiation, artifacts |
| CCTA | CT visualization of coronary arteries | Rule out CAD, anatomic assessment | ~95% | ~83% | Radiation, contrast nephropathy |
7. Clinical Decision-Making: Which Test to Choose?
- Initial evaluation: Exercise ECG in low-to-intermediate risk patients with interpretable baseline ECG.
- Poor ECG baseline / unable to exercise: Stress echo or MPI with pharmacologic stress.
- Need anatomical detail: CCTA for rule-out in low-to-intermediate risk patients.
- High-risk or confirmed CAD: Proceed directly to invasive coronary angiography.
8. Future Directions
- Hybrid imaging (PET/CT, SPECT/CT) combines anatomical and functional assessment.
- FFR-CT (Fractional Flow Reserve with CT): Non-invasive functional assessment of stenosis severity.
- Artificial intelligence in imaging analysis for improved accuracy.
- Ultra-low-dose CT reducing radiation burden.
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