Multiple guidelines and appropriate use criteria are available for cardiovascular stress testing with and without cardiac imaging.
Pretest probability is used to determine if cardiovascular stress testing is appropriate and whether cardiac imaging is also appropriate.5-10,15 The pretest probability of CAD is based on age, gender, and symptoms.5
Exercise stress testing without cardiac imaging
Wolk et al10 provided the 2013 multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease. An exercise stress test is recommended for patients exhibiting cardiac symptoms, including otherwise unexplained angina equivalent symptoms with normal or minor changes in resting ECG and no contraindications to exercise.5-10 Exercise stress testing is also recommended for patients without cardiac symptoms who underwent a percutaneous coronary intervention (PCI) (with a stent) procedure or a coronary artery bypass graft (CABG) more than 2 years prior and have not undergone an evaluation for CAD within the past 2 years [stress echocardiogram, SPECT MPI, PET MPI, CMR, coronary computed tomography angiography (CCTA), cardiac catheterization] and are able to exercise.6-8,10,15,17,18 Evidence-based guidelines also recommend an exercise stress test for patients with established CAD who experienced an acute coronary syndrome (ACS) event (ST segment elevation myocardial infarction [STEMI], a Non–ST segment elevation myocardial infarction [NSTEMI], or unstable angina) within the past 90 days provided that they did not undergo coronary angiography at the time of the acute event and are currently clinically stable and able to exercise.6,8,10
Exercise stress testing without cardiac imaging for patients who can exercise and stress testing with cardiac imaging for patients who are unable to exercise
Multiple articles address that the confounders of stress ECG interpretation include resting ST-segment depression, left ventricular hypertrophy with repolarization abnormalities, left bundle branch block, various medications, pre-excitation pattern such as Wolff-Parkinson-White, and ventricular paced rhythm.2,5,8,9,15,21 An exercise or pharmacological imaging study should be considered for patients with an abnormal resting ECG due to left bundle branch block, pre-excitation syndrome, left ventricular hypertrophy (LVH), new-onset atrial fibrillation, or digoxin therapy, because the accuracy of the exercise ECG in detecting provocable ischemia is reduced.2,5,10,12,13 An exercise or pharmacological imaging study should also be considered for patients with disease conditions associated with CAD (e.g., atherosclerotic abdominal aortic aneurysm, peripheral vascular disease, carotid artery disease, chronic renal failure) with no evaluation performed within the preceding 2 years.5,7,10,17
Shen et al16 provided the 2017 American College of Cardiology/American Heart Association guideline for the evaluation and management of patients with syncope. Stress testing is recommended for patients with an intermediate or high CHD risk (ATP III risk criteria) who have experienced syncope (an abrupt, transient, complete loss of consciousness) when cardiac etiology is suspected based on an initial evaluation, including history, physical examination, or ECG. An exercise stress test is recommended for patients who can exercise and pharmacological stress imaging is recommended for patients who are unable to exercise.6,8,10,15,16
The guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery states perioperative cardiac and long-term risks are increased in patients who are unable to perform 4 METs of work during daily activities.19 Perioperative myocardial ischemia and cardiovascular events were more common in those with poor functional status. Patients undergoing low-risk noncardiac surgery and patients undergoing elevated risk noncardiac surgery with moderate or greater functional capacity do not require cardiovascular stress testing. For patients undergoing elevated risk noncardiac surgery with poor (<4 METs) or unknown functional capacity and further testing will impact decision making or perioperative care, it may be reasonable to perform cardiovascular stress testing.
Fleisher et al19 recommends pre-operative cardiac evaluation in patients undergoing noncardiac surgery with an intermediate risk for surgery (cardiac risk 1-5%) or with a high risk for surgery (> 5% cardiac risk) and the results will affect patient management decisions. In this regard, exercise stress testing is recommended for patients who are able to exercise and pharmacologic stress testing for patients who are unable to exercise.
Stress testing with cardiac imaging
Pharmacological imaging studies may be appropriate for those patients who are unable to reach 75–100 percent of their age-predicted maximum heart rate by physiologic exercise.
The SPECT MPI is highly accurate to diagnose flow-limiting CAD and to stratify risk of ischemic heart disease events.9 A strength of SPECT is the availability of robust software programs for the interpretation of MPI. Hendel et al17 provided a multicenter assessment of the use of single-photon emission computed tomography myocardial perfusion imaging with appropriateness criteria. Dorbala et al24 has also provided SPECT MPI guidelines. Consistent with these guidelines, stress testing with cardiac imaging is recommended for patients without cardiac symptoms who underwent a PCI (with stent) procedure or a CABG more than 2 years prior and have not undergone an evaluation for CAD within the past 2 years [stress echocardiogram, SPECT MPI, PET MPI, CMR, coronary computed tomography angiography (CCTA), cardiac catheterization] and are unable to exercise.6-8,15,17,18 A stress test with cardiac imaging is also recommended for patients with cardiac symptoms who had a PCI procedure (with stent) or a CABG procedure more than 5 years ago and who have not undergone an evaluation for CAD within the past 2 years [stress echocardiogram, SPECT MPI, PET MPI, CMR, CCTA, cardiac catheterization].6-8,15,17
Evidence-based guidelines also recommend stress testing with cardiac imaging for patients experiencing new, recurrent, or worsening cardiac symptoms, including otherwise unexplained angina equivalent symptoms, and any of the following: a) Physical inability to perform a maximum exercise workload,2,5,6,8-10,15,20 b) New or previously unrecognized uninterpretable ECG,2,5,6,8-10 c) ECG is uninterpretable for ischemia due to any one of the following2,5,8,9,15,21: 1) Complete left bundle branch block (right bundle branch does not render ECG uninterpretable for ischemia); 2) Ventricular paced rhythm; 3) Pre-excitation pattern such as Wolff-Parkinson-White; 4) A > 1 mm ST segment depression (Not nonspecific ST/T wave changes); 5) Left ventricular hypertrophy (LVH) with repolarization abnormalities, also called LVH with strain (Not without repolarization abnormalities or by voltage criteria); or 6) Patient on digoxin therapy. Stress testing with cardiac imaging is also recommended for patients with a history of CAD based on a prior anatomic evaluation of the coronary arteries or a history of CABG or PCI.6,8,15
Consistent with evidence-based guidelines, stress testing with cardiac imaging is recommended for patients with the following conditions: a) Evidence or high suspicion of ventricular arrhythmias,6-8,10 b) Worsening or continuing symptoms in a patient who had a normal or submaximal exercise stress test and there is suspicion of a false negative result,20,22 c) Patients on beta blocker, calcium channel blocker, and/or antiarrhythmic medication when the documentation supports that an adequate workload may not be attainable to enable a fully diagnostic exercise study,2,5 d) History of false positive exercise stress test (e.g., one that is abnormal, but the abnormality does not appear to be due to macrovascular CAD),22 e) Evaluation of chest pain syndrome after revascularization or in patients with intermediate to high pre-test probability for CAD regardless of ECG interpretability or ability to exercise,7,8 and f) High pre-test probability for CAD regardless of ECG interpretability or the ability to exercise, and a decision to perform cardiac catheterization or other angiography has not already been made.7,8,10,15
Stress testing with cardiac imaging
The Lipinski et al article was a meta-analysis which showed that stress CMR provided excellent prognostic stratification of patients with known or suspected CAD.1 Patients with a negative stress CMR had a <1% annualized event rate for cardiovascular death or nonfatal myocardial infarction. Patients with a positive stress CMR had a 5% annualized event rate. The presence of late gadolinium enhancement (LGE) during CMR suggested an increased risk for major adverse cardiovascular events. This imaging modality not only provides assessment of ischemia and recognition of LGE but can also identify valvular heart disease and assess cardiac structure and function. Stress CMR is considered to be comparable to other stress testing modalities in patients who cannot exercise. The Leiner et al position paper supports that in addition to assessing for myocardial ischemia, CMR can also distinguish scar from hibernating myocardium, provide information about valvular function, the presence of myocardial fibrosis, the presence of morphological abnormalities, and provide an assessment of dynamic obstruction. This is especially valuable in patients in whom good quality echocardiography images could not be obtained due to technically difficult acoustic windows.3,4 The 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy indicates that while echocardiography continues to be the foundational imaging modality for patients with HCM, CMR will also be helpful in many patients, especially those in whom there is diagnostic uncertainty, poor echocardiographic imaging windows, or where uncertainty persists regarding decisions around implantable cardioverter-defibrillator (ICD) placement.4
The appropriate use criteria for echocardiography is a meta-analysis that addresses appropriate use of echocardiography.6 Stress echocardiography is recommended for asymptomatic patients with a coronary calcium Agatston score >400, for patients with new or worsening symptoms with a previous abnormal stress test and the inability to exercise. A stress echocardiography is also recommended for evaluating inducible ischemia in patients with an intermediate risk for coronary artery blockages and have established CAD, experienced an ACS event (STEMI, NSTEMI, or unstable angina) within the past 90 days provided that they did not undergo coronary angiography at the time of the acute event and are currently clinically stable. Additionally, stress echocardiography is recommended to assess chronic valvular disease, pulmonary hypertension, new, recurrent, or worsening left ventricular dysfunction/congestive heart failure, to assess patients without clear cardiac symptoms in the presence of an elevated cardiac troponin, and to evaluate patients with recent equivocal or borderline testing where ischemia remains a concern. Stress echocardiography, as well as myocardial perfusion imaging or cardiac magnetic resonance is also recommended to assess myocardial viability in patients with significant ischemic ventricular dysfunction (suspected hibernating myocardium) and persistent symptoms or heart failure such that revascularization would be considered.49 In addition, the guideline for the diagnosis and treatment of hypertrophic cardiomyopathy (HCM) addresses the use of stress echocardiography for the detection of dynamic LVOT obstruction.14
Cardiac involvement in sarcoidosis may lead to adverse outcomes such as advanced heart block, arrhythmias, cardiomyopathy, or death. Multiple articles support F-18 FDG PET MPI is indicated to diagnose cardiac sarcoidosis in patients who are unable to undergo MRI, have inconclusive MRI findings, or when high probability of disease exists even after a negative MRI. The PET MPI is also indicated to determine response to immunosuppressive therapy in patients diagnosed with cardiac sarcoidosis.15,41-48 The PET MPI can be safely performed on patients with intracardiac devices and advanced renal disease and is considered to be an appropriate tool to predict and assess response under therapy.41,44,46,47,51-53
Multiple articles address the increased risk for premature cardiovascular disease following organ transplantation.10,27-35 There are unique factors in organ transplant recipients that include underlying comorbidities and metabolic effects of immunosuppression.27 In this regard, the Ducloux et al study demonstrates the cumulative impacts of traditional and nontraditional cardiovascular risk factors in renal transplant recipients.28 Also, according to Gamba et al, cyclosporine, regardless of the blood cyclosporine levels, is the main risk factor for coronary artery disease.29 Additionally, Tepperman et.al noted that although immunosuppressive agents are sufficient to minimize allograft rejection and promote short-term survival after transplantation, a major limitation to longer-term survival is the development of allograft vasculopathy.30 Central to development of allograft vasculopathy is endothelial damage and subsequent dysfunction. The factors contributing to endothelial dysfunction include organ preservation solutions, ischemia and reperfusion injury, acute allograft rejection episodes, dyslipidemia, hypertension, diabetes mellitus, and the use of immunosuppressive drugs. Notably, many of the currently used immunosuppressants cause endothelial dysfunction after transplantation.
The Kazmirczak et al article found that regadenoson stress CMR imaging is safe and well tolerated in heart transplant recipients.36 An abnormal regadenoson stress CMR identifies heart transplant recipients at a higher risk for major adverse cardiovascular events. Also, Kan and Bangalore found that among renal transplant recipients, SPECT-MPI predicted risk of cardiovascular death and cardiovascular hospitalization events.38 The Sade et al article also concluded that echocardiographic coronary flow reserve is very sensitive for detecting cardiac allograft vasculopathy and increases the diagnostic accuracy of dobutamine stress echocardiography in heart transplant recipients.39 Additionally, Elhendy et.al found dobutamine stress myocardial perfusion imaging is a safe and feasible method for evaluation of coronary artery disease in heart transplant recipients.40 Evidence-based guidelines10 also recommend stress imaging prior to planned cardiac or other solid-organ transplant.
Situations in which cardiovascular stress testing is not recommended
Stress testing with or without imaging for pre-operative evaluation of asymptomatic patients undergoing intermediate or high risk noncardiac surgery would not be expected for patients 12 months following a normal stress echocardiography, SPECT MPI, PET MPI, CMR, coronary computed tomography angiography (CCTA), or cardiac catheterization.7,10,19 Also, utilization of SPECT MPI, PET MPI, stress echocardiography or CMR for the pre-operative evaluation of planned intermediate or high risk, noncardiac surgery, in the patient with normal or minor changes in resting ECG would not be expected for patients with no contraindications to exercise6-8,17,19
The review of the American Diabetes Association standards of medical care in diabetes 2018 states routine screening for CAD in asymptomatic patients is not recommended as it does not improve outcomes if atherosclerotic cardiovascular disease risk factors are treated. Screening is not recommended in part because high risk patients should already be receiving intensive medical therapy-an approach that provides benefit similar to that of invasive revascularization.11 The review states to consider investigations for CAD in the presence of atypical symptoms, signs and symptoms of associated vascular disease, or electrocardiogram abnormalities.
Absolute and relative contraindications to exercise testing are addressed by Henzlova and Gibbons.2,5 Although exercise testing is generally a safe procedure, both myocardial infarction and death have been reported at a rate of approximately 1 per 2500 tests. Therefore, it is vital to use good clinical judgement in decisions regarding which patients should undergo exercise testing.
Qaseem et al49 discussed the clinical practice guideline for diagnosis of stable ischemic heart disease and indicated pharmacologic stress imaging by MPI, echocardiography, or CMR are not recommended for patients with an interpretable ECG and who are able to exercise. Cardiovascular stress testing with or without cardiac imaging is also not recommended when a decision to perform cardiac catheterization or other angiography has already been made or for pre-operative evaluation for low risk noncardiac surgery. Also, only one type of stress test should be performed in patients who recently demonstrated coronary stenosis of uncertain functional significance in a major coronary branch on an anatomic imaging study (coronary angiogram or CCTA). Additionally, consistent with evidence-based guidelines, exercise testing or radiologic imaging performed within 2 years of PCI without specific symptoms (e.g., chest pain, ECG changes, etc.) is not recommended.8,17,18