Cardiac stress imaging can assess coronary perfusion, cardiac (including valvular) function, myocardium viability, and exercise capacity. 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. Results can further risk stratify, predict prognosis, and guide treatment in various cardiac pathologies.
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.
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.
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. 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.
American College of Cardiology Foundation (ACCF) and the American Society of Nuclear Cardiology (ASNC) Appropriate Criteria 
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):
American College of Cardiology Foundation Appropriateness Criteria Task Force and American Society of Echocardiography Appropriate Criteria 
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):
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). 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. Given its high negative predictive value, ETT remains the first line stress test according to the ACC/AHA guidelines for eligible patients. 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). 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. 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.
Imaging improves the sensitivity and specificity of identifying CAD. 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.
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.
Given limited studies on pregnant females, an exercise echocardiogram stress test is preferred in this population to avoid any unnecessary pharmacological or radiation exposure.
Stress Echo: (88% sensitivity, 83% specificity)
Stress Nuclear MPI: (86% Sensitivity, 74% specificity)
Stress Testing Not Indicated:
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.
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.
Methods of Cardiac Stress Testing 
Exercise Tolerance Testing
Stress Echocardiography (Echo)
Stress Myocardial Perfusion Imaging (MPI)
Complications can occur during cardiac stress testing, and these include:
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. ETT can also reveal chronotropic incompetence, the failure to increase heart rate appropriately, leading to exertional symptoms such as dizziness, which suggests conduction pathologies. The ability to achieve at least 10 METs on the ETT protends an excellent prognosis, regardless of the extent of coronary disease.
Duke treadmill score (DTS) is a prognostic tool summarizing the results of an ETT.
DTS = exercise time – (5 × ST deviation) – (4 × exercise angina)
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).
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.
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. The diffuse, multi-vessel ischemic disease may still show uniform uptake but can be detected by an increased left ventricular cavity size during stress. 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.
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.
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. 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). These attenuation artifacts will be fixed, but unlike scar, they will demonstrate preservation of wall thickening between diastole to systole on gated images. Other pathological conditions such as hypertrophic cardiomyopathy, severe LVH, and dilated or infiltrative cardiomyopathies may exhibit perfusion abnormalities on MPI not attributable to CAD. False-positive and false-negative results are common among women ETT.
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. 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.
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. 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. 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. Angiography can definitively diagnose CAD and offer therapeutic interventions such as percutaneous coronary intervention or coronary artery bypass graft revascularization.
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.
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.
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.
Echosonographers/Nuclear Imaging Technicians
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:
|||Mangla A,Oliveros E,Williams KA Sr,Kalra DK, Cardiac Imaging in the Diagnosis of Coronary Artery Disease. Current problems in cardiology. 2017 Oct; [PubMed PMID: 28870377]|
|||Miller TD,Askew JW,Anavekar NS, Noninvasive Stress Testing for Coronary Artery Disease. Heart failure clinics. 2016 Jan; [PubMed PMID: 26567975]|
|||Gibbons RJ,Balady GJ,Bricker JT,Chaitman BR,Fletcher GF,Froelicher VF,Mark DB,McCallister BD,Mooss AN,O'Reilly MG,Winters WL,Gibbons RJ,Antman EM,Alpert JS,Faxon DP,Fuster V,Gregoratos G,Hiratzka LF,Jacobs AK,Russell RO,Smith SC, ACC/AHA 2002 guideline update for exercise testing: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Journal of the American College of Cardiology. 2002 Oct 16; [PubMed PMID: 12392846]|
|||Gibbons RJ,Balady GJ,Beasley JW,Bricker JT,Duvernoy WF,Froelicher VF,Mark DB,Marwick TH,McCallister BD,Thompson PD Jr,Winters WL,Yanowitz FG,Ritchie JL,Gibbons RJ,Cheitlin MD,Eagle KA,Gardner TJ,Garson A Jr,Lewis RP,O'Rourke RA,Ryan TJ, ACC/AHA Guidelines for Exercise Testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). Journal of the American College of Cardiology. 1997 Jul; [PubMed PMID: 9207652]|
|||Garner KK,Pomeroy W,Arnold JJ, Exercise Stress Testing: Indications and Common Questions. American family physician. 2017 Sep 1; [PubMed PMID: 28925651]|
|||Brindis RG,Douglas PS,Hendel RC,Peterson ED,Wolk MJ,Allen JM,Patel MR,Raskin IE,Hendel RC,Bateman TM,Cerqueira MD,Gibbons RJ,Gillam LD,Gillespie JA,Hendel RC,Iskandrian AE,Jerome SD,Krumholz HM,Messer JV,Spertus JA,Stowers SA, ACCF/ASNC appropriateness criteria for single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI): a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group and the American Society of Nuclear Cardiology endorsed by the American Heart Association. Journal of the American College of Cardiology. 2005 Oct 18; [PubMed PMID: 16226194]|
|||Douglas PS,Khandheria B,Stainback RF,Weissman NJ,Peterson ED,Hendel RC,Stainback RF,Blaivas M,Des Prez RD,Gillam LD,Golash T,Hiratzka LF,Kussmaul WG,Labovitz AJ,Lindenfeld J,Masoudi FA,Mayo PH,Porembka D,Spertus JA,Wann LS,Wiegers SE,Brindis RG,Douglas PS,Hendel RC,Patel MR,Peterson ED,Wolk MJ,Allen JM, ACCF/ASE/ACEP/AHA/ASNC/SCAI/SCCT/SCMR 2008 appropriateness criteria for stress echocardiography: a report of the American College of Cardiology Foundation Appropriateness Criteria Task Force, American Society of Echocardiography, American College of Emergency Physicians, American Heart Association, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance endorsed by the Heart Rhythm Society and the Society of Critical Care Medicine. Journal of the American College of Cardiology. 2008 Mar 18; [PubMed PMID: 18342240]|
|||Anderson KM,Murphy DL,Balaji M, Essentials of noninvasive cardiac stress testing. Journal of the American Association of Nurse Practitioners. 2014 Feb; [PubMed PMID: 24420707]|
|||Ladapo JA,Blecker S,O'Donnell M,Jumkhawala SA,Douglas PS, Appropriate Use of Cardiac Stress Testing with Imaging: A Systematic Review and Meta-Analysis. PloS one. 2016; [PubMed PMID: 27536775]|
|||Hendel RC,Berman DS,Di Carli MF,Heidenreich PA,Henkin RE,Pellikka PA,Pohost GM,Williams KA, ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 Appropriate Use Criteria for Cardiac Radionuclide Imaging: A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine. Journal of the American College of Cardiology. 2009 Jun 9; [PubMed PMID: 19497454]|
|||Ketteler T,Krahwinkel W,Gödke J,Wolfertz J,Scheuble L,Hoffmeister T,Gülker H, Stress echocardiography: personnel and technical equipment. European heart journal. 1997 Jun; [PubMed PMID: 9183610]|
|||Dzenkeviciute V,Sapoka V,Kasiulevicius V,Rinkuniene E,Steponeniene R,Einikyte R,Dapkeviciute A, Value of Duke treadmill score in predicting coronary artery lesion and the need for revascularisation. Kardiologia polska. 2017; [PubMed PMID: 28281733]|
|||Bourque JM,Beller GA, Value of Exercise ECG for Risk Stratification in Suspected or Known CAD in the Era of Advanced Imaging Technologies. JACC. Cardiovascular imaging. 2015 Nov; [PubMed PMID: 26563861]|