Continuing Education Activity

Cardiac stress imaging is a noninvasive modality used in evaluating coronary artery disease, myocardium viability, and exercise capacity. This activity reviews cardiac stress imaging and highlights the role of the interprofessional team in evaluating and treating patients who undergo workup for coronary artery disease and other cardiac functional abnormalities.

Objectives:

• Identify the screening indications for cardiac stress imaging.
• Describe the classic categorization of chest pain as typical, atypical, or non-cardiac, as it applies to pre-test probability risk stratification for cardiac stress imaging.
• Outline the management considerations for patients needing stress testing, particularly the pros and cons of choosing each stress imaging modality.
• Summarize the stress image findings associated with coronary artery disease and management options.

Introduction

Cardiac stress imaging can assess coronary perfusion, cardiac (including valvular) function, myocardium viability, and exercise capacity.[1] Stress can be induced pharmacologically or through physical exercise. Imaging modalities include echocardiography and nuclear myocardial perfusion imaging with either single-photon emission computed tomography (SPECT) or positron emission tomography (PET) scanning. Electrocardiogram (EKG) exercise stress testing can offer a sufficient ischemic evaluation for select patients, but imaging modalities offer more information and are often preferred. The different imaging modalities and modes of stress each have advantages and disadvantages when selecting the most appropriate test for each patient. The definitive diagnosis of coronary artery disease (CAD) is made by the presence of at least 50 to 70% stenosis of at least one epicardial vessel on coronary angiography. Stress testing is not diagnostic of CAD, as it only implies evidence of stenosis through functional assessments. However, the results can increase or decrease the probability of CAD, termed post-test likelihood, and guide decisions regarding pursuing invasive coronary angiography.[2] Results can further risk stratify, predict prognosis, and guide treatment in various cardiac pathologies.[3]

An ischemic evaluation typically is warranted when patients present with clinical concerns for angina or new heart failure suggesting coronary artery disease. Chest pain is categorized as typical angina, atypical angina, or non-cardiac chest pain, depending on the clinical characteristics. These characteristics include 1) substernal chest discomfort, 2) worsened with exertion or stress, and 3) relieved by rest or nitroglycerine. Typical angina pain meets all three characteristics, and atypical meets only two. If the pain has none or only one of the above characteristics, it is considered non-anginal/non-cardiac chest pain.[4][5] 

Based on the above clinical chest pain characteristics and patient factors such as age, gender, and comorbidities, each patient can be assigned a pre-test probability, ranging from low (<10%), intermediate (10 to 90%), to high (>90%) pretest-probability of having coronary artery disease according to the American College of Cardiology and American Heart Association (ACC/AHA). Stress testing is ideal for the intermediate-risk patient, as the test outcome has the highest potential to impact CAD post-test likelihood in this group. A positive test result in the high-pretest-risk patient group would not add much to CAD's likelihood, and these patients are often referred directly to an angiography without stress testing.[4]

Anatomy and Physiology

Coronary angiography, the traditional gold standard for diagnosing coronary artery disease(CAD), offers visualization of the coronary anatomy and atherosclerotic stenosis. A 50 to 70% or greater stenosis is considered diagnostic of CAD.[2] The less invasive stress imaging modalities cannot explicitly depict the coronary anatomy, but they demonstrate functional ischemia of vascular territories, allowing the inferences of stenosis in respective vessels. For example, a regional wall motion abnormality on echocardiography or a perfusion defect in MPI during stress suggests ischemic pathology within the vessel supplying that myocardial territory.[1]

Indications

ACC/AHA 1997[4] and Updated 2002 Guideline Indications for Exercise Stress Testing:[3]

Class I

1. Patients (including those with right bundle branch block or less than 1 mm resting ST depression) having an intermediate pretest probability of CAD based on gender, age, and symptoms 
2. Patients with known CAD who have a change in clinical status
3. Low-risk (of short term death or myocardial infarction (MI)) unstable angina patients who have been free of active symptoms for at least 8 to 12 hours
4. Intermediate-risk (of short term death or MI) unstable angina patients who have been free of active symptoms for at least 2 to 3 days
5. Post-MI (>4 days from the event) patients for evaluation of prognostic assessment, activity prescription, and evaluation of medical therapy 

Class IIa

1. Patients with intermediate-risk (of short term death or MI) unstable angina patients who have normal initial cardiac markers (drawn at least 6-12 hours after onset of symptoms) and serial EKGs without dynamic changes  
2. Evaluation of known or suspected exercise-induced arrhythmias 
3. After discharge in post-revascularization patients for evaluation of prognostic assessment, activity prescription, and evaluation of medical therapy

Class IIb 

1. Patients who have a high or low pretest probability of CAD by age, symptoms, and gender
2. Exercise capacity evaluation of patients with valvular heart disease (excluding severe aortic stenosis) 

American College of Cardiology Foundation (ACCF) and the American Society of Nuclear Cardiology (ASNC) Appropriate Criteria [6]

A mean score of 7-9 implies society recommends stress nuclear MPI as the appropriate test for the given indication, whereas 1-3 indicates inappropriate. 

Recommended as Appropriate (Appropriateness Score (AS) 7-9):

1. The intermediate to high pretest probability of CAD for patients with stable angina, an uninterpretable EKG, and inability to exercise (AS 9)
2. The intermediate pretest probability of CAD for patients with stable angina, an interpretable EKG, and ability to exercise (AS 7)
3. The high pretest probability of CAD for patients with stable angina, an interpretable EKG, and ability to exercise (AS 8)
4. The intermediate pretest probability of CAD for patients with acute chest pain but negative cardiac enzymes and no STE on EKG (AS 9) (AS 1 for high pretest probability with ST elevations)
5. Prior indeterminant exercise treadmill test (AS 9)
6. New-onset heart failure or LV systolic dysfunction and moderate Framingham risk of coronary heart disease with stable angina (AS 8) and without chest pain symptoms (AS 7.5)

American College of Cardiology Foundation Appropriateness Criteria Task Force and American Society of Echocardiography Appropriate Criteria [7]

A mean score of 7-9 implies society recommends stress echocardiography as the appropriate test for the given indication, whereas 1-3 indicates inappropriate. 

Recommended as Appropriate (Appropriateness Score(AS) 7-9):

1. The low pretest probability of CAD for patients with stable angina, with either an uninterpretable EKG or inability to exercise (AS 7)
2. The intermediate pretest probability of CAD for patients with stable angina, with an interpretable EKG and inability to exercise (AS 7)
3. The intermediate pretest probability of CAD for patients with stable angina, with either an uninterpretable EKG or inability to exercise (AS 9)
4. The high pretest probability of CAD for patients with stable angina, regardless of EKG interpretability or ability to exercise (AS 7)
5. The intermediate pretest probability of CAD for patients with acute chest pain but negative cardiac enzymes and no dynamic EKG changes (AS 8) (AS 1 for high pretest probability with ST elevations) 
6. Prior equivocal exercise treadmill test (AS 8)
7. The intermediate pretest probability of CAD and new-onset heart failure and normal LV systolic function for patients with stable angina (AS 8) 
8. Moderate Framingham risk and new-onset heart failure and normal LV systolic function for patients without chest pain (AS 7) 

Selecting the Best Stress Method and Imaging Modality:

Most intermediate-pretest probability patients with an interpretable EKG capable of exercising are candidates for exercise treadmill testing (ETT) (Class I, LOE A in ACC/AHA guidelines). Uninterpretable EKGs include patients with left bundle branch block (LBBB), paced-rhythm, pre-excitation, digoxin use, and a resting STD >1 mm, which is common in left ventricular hypertrophy (LVH).[4][1] Due to variations such as gender and age, ETT shows a wide range of accuracy but has a mean sensitivity of 67% and a mean specificity of 72% for new CAD diagnosis.[4] Given its high negative predictive value, ETT remains the first line stress test according to the ACC/AHA guidelines for eligible patients.[8] The European guidelines recognize the risks of only moderate 67% sensitivity in the more concerning intermediate-pretest probability patients. They further divide the ACC/AHA intermediate group (10 to 90%) into a lower-intermediate (15 to 65%) and higher-intermediate (66 to 85%) pretest probabilities and recommend proceeding straight to imaging in the higher-intermediate group (Class I, LOE B).[1] Women are more likely to have false-positive and false-negative ETT, and therefore some providers are more likely to proceed straight to imaging in women.[1][8] Furthermore, patients with uninterpretable ETT, high suspicion despite negative ETT (or potential negative ETT), who are not candidates for ETT, or image-specific functional information are needed to warrant stress testing imaging.[1][8]

Imaging improves the sensitivity and specificity of identifying CAD.[2] Both echocardiography and nuclear imaging can be done with exercise stress, though echo is more technically challenging, given the heart rate declines during image acquisition. When pharmacologically stressing, dobutamine, a beta-agonist, is often used for stress echocardiography, and regadenoson, a vasodilator, is often used for nuclear imaging.[2][1]

Stress can be induced via treadmill or bike exercise or pharmacologic agents. Pharmacologic stress is reserved primarily for patients with functional impairments such as arthritis or peripheral neuropathy. Exercise is preferred to pharmacological when able, as it offers additional prognostic information. Symptom limiting exercise capacity less than five metabolic equivalents (METS) carries a poor prognosis.[2]

Given limited studies on pregnant females, an exercise echocardiogram stress test is preferred in this population to avoid any unnecessary pharmacological or radiation exposure.[8] 

Stress Echo: (88% sensitivity, 83% specificity)  

Advantages

• No radiation exposure, ideal in young females
• Cost-effective
• Additional insight to structural, such as valvular or pericardial, pathology, diastolic function, and pulmonary pressures
• Also offers viability assessment, identifying stunned and hibernating myocardium[1]

Disadvantages

• Post-exercise imaging is time-sensitive, need to acquire images within 1 minute of exercise termination
• Highly dependent on sonographer and interpreter skills
• Diagnostic accuracy reduced by excessive tachycardia, arrhythmias, conduction abnormalities, COPD, obesity, or other cause of poor sonographic windows[1][5]

Stress Nuclear MPI: (86% Sensitivity, 74% specificity) 

Advantages

• Most sensitive for detecting single-vessel disease
• Best for patients with LBBB or pacemakers causing abnormal septal motion

Disadvantages

• Radiation exposure, with radioactivity for 3 to 4 days post-procedure
• Diagnostic accuracy reduced by arrhythmias and soft-tissue attenuation[5] 
• 300 lbs weight limit for most machines
• Severe claustrophobia may prohibit use[8] 

Stress Testing Not Indicated:

• Patients who have a low risk of coronary artery disease[5]
• Pre-operative risk stratification for non-cardiothoracic, non-vascular surgery for patients (even with CAD) able to perform at least four metabolic equivalents (METS) of exertion, such as walking up one flight of stairs[5] 
• The three most common inappropriate uses for stress imaging are pre-operative evaluation, symptomatic (often low-risk) patients with an exercise treadmill test suitable EKG, and asymptomatic patients[9]

Contraindications

Absolute Contraindications for cardiac stress imaging are:[5][4][10]

1. Acute myocardial infarction (MI), MI < 2 days prior, endocarditis, pericarditis, or aortic dissection.
2. Acute decompensated heart failure
3. Symptomatic, severe aortic stenosis
4. Arrhythmia with hemodynamic instability
5. Ongoing, symptomatic unstable angina
6. Specific to dobutamine stress: Hypertrophic obstructive cardiomyopathy and history of glaucoma

Equipment

Standard Equipment:[8][11]

1. Ultrasound machine with Doppler (for echocardiography) 
2. or
3. Single-photon emission computed tomography (SPECT) scanner or positron emission tomography (PET) scanner (for myocardial perfusion imaging (MPI))
4. 12 Lead EKG and telemetry system for continuous monitoring
5. Blood pressure cuff (manual or automatic)
6. Treadmill or stationary bike (if exercise) 
7. or
8. intravenous medication system, and appropriate medications (if pharmacologic) 
9. If MPI will need an intravenous medication system and radioactive tracer 
10. Emergency equipment (crash cart and defibrillator) in the vicinity

Personnel

Stress imaging may be performed directly by a provider trained in stress imaging or by a nurse, exercise physiologist, or medical technician operating under the provider's supervision. Sonographers and nuclear technicians trained in image acquisition and machine operations for the respective modalities are the primary technical personal. A cardiologist trained in echocardiography and/or nuclear imaging provides the interpretations.[4][11]

Preparation

Patient instructions: No food/drink for 4 to 8 hours before any stress test. No caffeine or phosphodiesterase inhibitors for 48 hours before the nuclear MPI regadenoson stress test. No beta-blockers on the day of dobutamine stress echocardiogram.[8]

Technique or Treatment

Methods of Cardiac Stress Testing [8]

Exercise Tolerance Testing

• Uses a standardized exercise protocol, most commonly the 7-staged Bruce protocol 
• The Bruce protocol involves incremental increases in walking speed and incline on a treadmill every 3 minutes until 85% of the maximal predicted heart rate is achieved (maximal predicted heart rate = 220-patient age)
• EKG telemetry rhythms, hemodynamic changes, and clinical responses to exercise are monitored before, during, and after exercise[8]

Stress Echocardiography (Echo)

• Stress is induced with either exercise or pharmacologically with dobutamine. 
• Up titrate dobutamine from 5 to 10 mcg/kg/min, increasing by 10 mcg/kg/min every 3 min to a total of 40 to 50 mcg/kg/min until 85% of maximum predicted heart rate is achieved (220-age)[2][8]
• Side effects: chest pain, nausea, vomiting, flu-like symptoms, arrhythmias [2] 
• Baseline echo is obtained and used as rest images.
• Exercise stress echo is obtained immediately after achieving the patient’s goal heart rate, ideally within 1 minute.[8]
• Pharmacologic stress echo is obtained during the infusion of dobutamine.

Stress Myocardial Perfusion Imaging (MPI)

• Stress is induced with either exercise or pharmacologically with regadenoson.
• 0.4mg IV push over 10 seconds
• Side effects: bronchospasm, flushing, headache, nausea, chest discomfort[2] 
• Isotope options include thallium-201 (Tl-201), technetium-99 sestamibi (Tc-99m), or technetium-99 tetrofosmin 
• Images are obtained before, during, and after stress (each scan takes about 20minutes).[8] 
• Obese patients may need a 2-day test, with stress and post-stress rest images each accompanied by a low-dose tracer injection.
• Imaging may be obtained by SPECT or PET scan.[1]

Complications

Complications can occur during cardiac stress testing, and these include:

1. Cardiopulmonary Arrest
2. Myocardial infarction
3. Hypotension/Hypertension
4. Arrhythmias
5. Bronchospasm
6. Adverse or allergic reactions to isotope/pharmacologic agent[8]

Clinical Significance

Exercise EKG Stress Test (Exercise Treadmill Test, ETT)

Clinical interpretation provides information on exercise capacity (if not pharmacologic) and stress-induced symptoms, hemodynamic changes, and electrocardiogram abnormalities. Recurrence of angina, hypotension, ventricular arrhythmias, and concerning EKG changes such as horizontal or downsloping ST depression > 1 mm for at least 60-80 ms suggest ischemic coronaries, constituting a positive test. Unlike ST elevations, ST depressions do not localize to specific vessels but still indicate ischemic disease needing further evaluation with image testing or coronary angiography.[8] ETT can also reveal chronotropic incompetence, the failure to increase heart rate appropriately, leading to exertional symptoms such as dizziness, which suggests conduction pathologies.[5] The ability to achieve at least 10 METs on the ETT protends an excellent prognosis, regardless of the extent of coronary disease.[8]

Duke treadmill score (DTS) is a prognostic tool summarizing the results of an ETT.  

DTS = exercise time – (5 × ST deviation) – (4 × exercise angina)

• Exercise angina is defined as follows : 0 = none, 1 = non-limiting, 2 = exercise-limiting
• DTS >= 5 is low-risk, –10 to +4 is moderate risk, and <= -11 high-risk[12] 
• Low-risk= 0.25% 1-year mortality; 40.1% risk of single-vessel 75% stenosis
• Moderate-risk= 1.25% 1-year mortality; 67.3% risk of single-vessel 75% stenosis
• High-risk= 5.25% 1-year mortality; 99.6% risk of single-vessel 75% stenosis[13]

Stress Echocardiography:

A normal stress echocardiography test demonstrates global myocardial normokinesis at rest and then a normokinetic or hyperkinetic response to stress. Regional wall motion dysfunction (hypokinetic, dyskinetic, akinetic) that occurs at rest and stress represents scar tissue, likely from a prior infarct. Dysfunction that occurs only during stress suggests ischemia. Dysfunction present at rest, which improves at minimal stress and then worsens again at peak stress, indicates viable hibernating myocardium. Dysfunction at rest with sustained improvement on various levels of stress predicts stunned myocardium. Negative stress echocardiography test confers a 0.5% to 0.8% 1-year risk of cardiac death or nonfatal myocardial infarct (MI).[1] 

Stress Nuclear (SPECT-MPI and PET-MPI):

As a potent coronary vasodilator acting on the A2A receptor, regadenosin increases significantly more flow to healthy vessels than obstructed vessels. This imbalance of blood blow is detected as a perfusion defect in a diseased vessel territory, ischemic EKG changes, or recurrence of symptoms.[8] 

A normal SPECT stress demonstrates global, uniform isotope uptake at rest and then uniformly increased uptake at stress. Regional reductions in uptake during both stress and rest, termed a fixed defect, suggest scar tissue likely secondary to infarct. A relatively lower increase in tracer uptake in specific vascular territories during stress suggests reduced blood flow from stenosed coronary vessels.[1] The diffuse, multi-vessel ischemic disease may still show uniform uptake but can be detected by an increased left ventricular cavity size during stress.[8] Myocardial viability can be assessed with additional images at 18 to 24 hours post initial scan. Regions that on initial resting images lacked uptake will demonstrate a delayed uptake on re-imaging if the myocardium is viable since functional N-K-ATPase in living myocyte cell membranes will eventually uptake tracer, termed a reversible resting defect. Negative stress SPECT-MPI confers a 0.85% 1-year risk of cardiac death or MI. In a clinically stable patient without new symptoms, a normal SPECT-MPI affords a five year warranty period. Worse perfusion impairments, worse ejection fractions, and worse wall motion correlate with an increased likelihood of an adverse cardiac event.[1] 

Like SPECT, PET offers perfusion information and provides more quantitive measures of such and metabolism. PET can more precisely identify perfusion defect location, severity, and extend, including assessing the distal coronary microcirculation. While PET is more accurate than SPECT with relative immunity to attenuation artifacts, its higher expense and infrequent availability make it less commonly used.[1]

Cautions

False Positives 

Patients with LBBB or RV pacing are best evaluated with vasodilator MPI. In LBBB or RV-paced patients, the septum contracts later than the rest of the LV, requiring less blood flow. This physiologic septal hypoperfusion is exaggerated with exercise and reduced by a vasodilator. Therefore vasodilator MPI is preferred to exercise to avoid false positives.[1] Stress MPI can produce false-positive fixed defect signals from tissue attenuation in the inferior wall distribution due to diaphragmatic elevation (most common in men) or anterior wall distribution due to large breast tissue (most common in women).[8] These attenuation artifacts will be fixed, but unlike scar, they will demonstrate preservation of wall thickening between diastole to systole on gated images.[1] Other pathological conditions such as hypertrophic cardiomyopathy, severe LVH, and dilated or infiltrative cardiomyopathies may exhibit perfusion abnormalities on MPI not attributable to CAD.[1] False-positive and false-negative results are common among women ETT.[1][8] 

False Negatives

False-negative results are common in older women with small LV cavities since LVH, and their hyperdynamic left ventricular function impairs the sensitivity of both stress echo and stress NPI to detect abnormalities.[1] False-negative MPI can occur in a triple vessel or left main disease if only relative perfusion is assessed since a balanced perfusion reduction may be misread as normal.[1] 

Management of Positive Test

All positive stress tests warrant a discussion with the patient regarding further revaluation. A positive exercise treadmill test is followed with either stress imaging or high enough concern for patients interested in possible therapeutic interventions directly to coronary angiography. Similarly, a positive stress imaging test indicates a consideration for coronary catheterization.[8] The ACC/AHA apply post-test results to prognostic classifications based on given stress image test findings. The post-test classifications describe mortality risk, include low (<1%), intermediate (1 to 3%), and high (>3%) 1-year mortality risk. ACC/AHH recommends coronary angiography be performed in high-risk post-test patients, observation/medical management in low-risk post-test patients, and further evaluation and individualized clinical judgment in intermediate-risk post-test patients.[2] Providers must caution over-reliance on stress image findings, as each patient's clinical characteristics, including symptoms, CAD risk factors, and exercise capacity, also significantly impact risk profiles and management choices.[2] Angiography can definitively diagnose CAD and offer therapeutic interventions such as percutaneous coronary intervention or coronary artery bypass graft revascularization.[8]

Enhancing Healthcare Team Outcomes

Provider risk stratifies patients presenting with signs and symptoms of new or progressive CAD to deliver early, appropriate preventative and interventional patient care. Initial history and physical exam can gather data on risk factors and clinical signs of coronary disease. All health professional team members, including nurses, nurse practitioners, primary care providers, provider assistants, and cardiologists, must be aware of early clinical signs and CAD symptoms to help facilitate early evaluation. A high index of CAD suspicion in at-risk populations and early investigation helps reduce adverse cardiac events and improve quality of life.[8]

No large, randomized trial compares all stress imaging modalities to identify a superior choice. A meta-analysis found that negative echocardiography and MPI stress tests accurately identified patients with a low yearly risk of myocardial infarction or cardiac death. Guidelines proposed by major national societies, such as the American College of Cardiology and American Heart Association (ACC/AHA), American College of Cardiology Foundation (ACCF) and the American Society of Nuclear Cardiology, American Society of Echocardiography, all help providers apply the best diagnostic testing, including stress imaging, to provide optimum evidence-based patient care.[3][4][7][6] 

Recommendations on image selection focus on specific patient factors (specified in previous sections) and on the local facility's factors, including the training of those interpreting tests, the experience and skills of the sonographers or nuclear technicians, and the center's overall volume of tests. This highlights each member of the health care team's importance in delivering effective stress testing, as each member must be up-to-date, competent, and complementary to the team. A collaborative approach among various health care providers and shared-decision making with the patient allows for optimal medical care.[2]

Nursing, Allied Health, and Interprofessional Team Interventions

Nurses/Medical Assistants

1. Verify correct patient information in the electronic medical record and completion of the patient consent form. 
2. Verify the correct placement of 12-lead EKG, blood pressure cuff, and pulse oximetry for monitoring. 
3. Establish IV access for nuclear medication delivery/pharmacologic stress medication delivery.
4. Monitor the patient during the procedure.

Echosonographers/Nuclear Imaging Technicians

1. Operate imaging equipment and perform image acquisition with either an ultrasound machine or nuclear scanner (SPECT or PET) 
2. Monitor the patient during the procedure.[11]

Nursing, Allied Health, and Interprofessional Team Monitoring

Monitor vital signs, EKG changes, and patient symptoms during, before, and after the stress test.

Terminate the test and alert a provider if any concerning findings develop such as:

1. ST elevations >1 mm in leads without Q waves (other than V1 or AVR)
2. Moderate to severe angina
3. Near syncope
4. Cyanosis or decreasing oxygen saturation
5. Sustained ventricular tachycardia
6. Drop-in systolic blood pressure >10 mmHg from baseline
7. Patient desires to stop [4]