IIb C N/A For annual surveillance Exercise or pharmacological stress with nuclear MPI, Echo, or CMR or CCTA Any Any Any III: No Benefit C (10, 12, 15) a) ,5-y intervals after CABG, or b) ,2-y intervals after PCI *Patients are candidates for exercise testing if they are capable of performing at least moderate physical functioning (ie, moderate household, yard, or recreational work and most activities of daily living) and have no disabling comorbidity. Patients should be able to achieve 85% of age-predicted maximum heart rate. CABG indicates coronary artery bypass graft surgery; CCTA, cardiac computed tomography angiography; CMR, coronary magnetic resonance; COR, class of recommendation; CCTA, computed tomography angiography; CMR, cardiac magnetic resonance; ECG, electrocardiogram; Echo, echocardiography; LOE, level of evidence; MPI, myocardial perfusion imaging; N/A, not available; PCI, percutaneous coronary intervention; and SIHD, stable ischemic heart disease. Fihn et al Stable Ischemic Heart Disease: Full Text e431 Class IIa 1. Nuclear MPI, echocardiography, or CMR with ei- ther exercise or pharmacological stress can be useful for follow-up assessment at 2-year or longer inter- vals in patients with SIHD with prior evidence of silent ischemia or who are at high risk for a recur- rent cardiac event and a) are unable to exercise to an adequate workload, b) have an uninterpretable ECG, or c) have a history of incomplete coronary revascularization.10,12,15 (Level of Evidence: C) Class IIb 1. Standard exercise ECG testing performed at 1-year or longer intervals might be considered for follow-up assessment in patients with SIHD who have had prior evidence of silent ischemia or are at high risk for a recurrent cardiac event and are able to exercise to an adequate workload and have an interpretable ECG. (Level of Evidence: C) 2. In patients who have no new or worsening symptoms or no prior evidence of silent ischemia and are not at high risk for a recurrent cardiac event, the useful- ness of annual surveillance exercise ECG testing is not well established. (Level of Evidence: C) Class III: No Benefit 1. Nuclear MPI, echocardiography, or CMR, with ei- ther exercise or pharmacological stress or CCTA, is not recommended for follow-up assessment in pa- tients with SIHD, if performed more frequently than at a) 5-year intervals after CABG or b) 2-year intervals after PCI.10,12,15 (Level of Evidence: C) See Online Data Supplement 1 for additional data on nonin- vasive testing in known SIHD: asymptomatic (or stable symptoms). 6.3.3. Factors Influencing the Use of Follow-Up Testing The appropriateness of performing noninvasive testing in patients who either are asymptomatic or have stable symp- toms (ie, routine surveillance testing) depends on factors related to the likelihood of significant findings, such as the patient s risk for rapidly advancing disease, propensity to have silent ischemia, and length of time since revasculariza- tion. The data supporting follow-up testing are sparse and insufficient to support routine, repeat testing in asymptomatic individuals. However, evidence exists that persistent ische- mia on testing is a prognostically poor finding. Exploratory data from a small cohort of 314 patients with SIHD enrolled in the COURAGE trial nuclear substudy revealed that a reduction in the ischemic myocardium is associated with an (unadjusted) reduction in the incidence of death or MI combined.306 In the BARI 2D trial, at 1 year of follow-up, more extensive and severe stress myocardial perfusion SPECT abnormalities were associated with higher rates of death or MI.276 There are, however, several circumstances in which a decision to perform follow-up testing is thought to be warranted in the absence of a change in clinical status, although data supporting this approach are limited. These circumstances include, but are not limited to, evaluation of incomplete revascularization, assessment of the adequacy of medical therapy by provocative exercise testing, a substantial change in risk profile, or the need to reevaluate coronary status in anticipation of major noncardiovascular surgery when the patient s exercise capacity is limited or unknown (although revascularization in this circumstance has not been shown to reduce the risk of perioperative cardiovascular complications), as detailed in the ACCF/AHA Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery Guideline.1250 Care should be taken when interpreting paired testing results to incorporate not only the change in the extent and severity of ischemia but also the workload at onset and total exercise capacity achieved, as these factors relate to the patient s symptom burden and functional correlates in daily life. Outside of such special circumstances, routine periodic testing is not recommended in patients who are at low risk for progression or had overt symptoms on initial presentation (ie, those without known silent ischemia) or very early after revascularization. In addition to a lack of evidence for testing to detect ischemia, currently there is also little research to support exercise stress testing for risk assessment in asymp- tomatic patients with known CAD, except for cardiac reha- bilitation and exercise prescription purposes (Section 4.4.1.4.). 6.3.4. Patient Risk and Testing By using clinical, noninvasive, and invasive data acquired during the initial evaluation and subsequently, recommenda- tions about stress testing in patients with known SIHD can be formulated on the basis of the following considerations: In the absence of a change in clinical status, patients with a low projected annual mortality rate (,1%) are those with low-risk Duke treadmill scores, either without imaging or with nega- tive imaging findings, whose 4-year cardiovascular survival rate approximates 99%. The low-risk category also includes patients with normal stress imaging who lack adverse prog- nostic characteristics, such as diabetes mellitus or prior MI. Younger women without diabetes mellitus or a prior MI who have normal stress nuclear MPI remain at very low risk for as long as 7 to 9 years,307 depending on specific clinical characteristics, and probably do not require repeat stress imaging during that period in the absence of changes in Data are more limited with regard to the value of serial testing strategies in patients at intermediate risk of cardiac mortality (1% to 3% per year). Follow-up testing probably should be performed only if decisions about a change in pharmacological management, level of exercise, or revascu- larization will be influenced directly by the test result or if the patient has persistent symptoms despite adequate GDMT. Thus, in the patient with known SIHD, the goal of repeat testing is the assessment of residual ischemic burden after optimization of GDMT or the consideration of revasculariza- tion as a result of failed optimal medical management. Furthermore, to be considered significant, findings should be outside the expected range of variability of test results, which is approximately 5% for stress nuclear MPI,306,366 such that patients move into a higher or lower risk category. Even for high-risk patients, the value of annual exercise testing (or serial exercise testing at alternative intervals) in the absence of a change in symptoms has not been studied adequately. Yearly exercise testing could be useful in patients with SIHD who have .3% risk of mortality per year, because a marked decrease in exercise capacity or a marked increase in ischemic burden can warrant reevaluation of the medical regimen or interventional plan. Examples of such patients are those with a high-risk Duke treadmill score, patients with an EF ,50% and significant CAD in .1 major vessel, patients with diabetes mellitus, and those with multivessel disease who have not undergone CABG. Some data also suggest that ischemic burden might be useful in targeting ischemia-guided revascularization. In a substudy of the COURAGE trial, the overall event-free survival rate was 86.6% in patients with $5% reduction in ischemic myocardium versus 75.3% in those without significant reduction in ischemic burden after 6 Although this trial substudy was not powered to examine differences in clinical outcomes, the results are similar to the BARI 2D trial, in which patients with high myocardial jeopardy scores randomized to CABG had fewer cardiovas- cular events (AMI and composite endpoint of all-cause mortality or MI and cardiac death or MI) than those with high scores who received only medical therapy.276,409 6.3.5. Stability of Results After Normal Stress Testing in Patients With Known SIHD The durability of information gained from a stress test over time varies widely according to the characteristics of the patients and the type of test performed. Among patients with several clinical risk factors and negative stress imaging studies, the relative hazard for cardiac death or MI can increase after a 2-year follow-up time period, whereas among other groups, the risk remains low through 2 years and can be safely assumed to remain low for an extended period of time. In 1 large single-site study, the factors associated with an earlier increase in risk included diabetes mellitus, male sex, increased age (ie, $70 years), a history of previous MI or revascularization, and having undergone a pharmacological stress test rather than an exercise test327 (Figure 15). The relationships were, however, complex and covarying. Impor- tantly, among patients who were younger and female and did not have diabetes mellitus or a history of MI or revascular- ization, the annual risk of adverse cardiovascular events was predicted to remain ,1% for as long as 9 years, on the basis of hard events observed during the 2-year follow-up period. In contrast, in an 80-year-old man with a normal pharmaco- logical stress study, the risk of an adverse event rose to .1% in ,1 year after an index-negative perfusion evaluation. 6.3.6. Utility of Repeat Stress Testing in Patients With Known CAD The interpretation of repeat testing should be based on a threshold change value that exceeds the expected variability in test results, even in patients at high risk for recurrent events, and especially in those with no interval clinical change.1244 Although the variability of exercise and stress testing results is not well established,306,1251 factors such as differences in day-to-day operations in the same laboratory, interobserver variability, and differences between practices in different imaging laboratories are important contributory factors in observed differences in serial testing. A 5% change in the percent of ischemic myocardium (based on extent and severity) has been suggested by some investigators as a threshold that indicates clinically significant change for stress nuclear MPI.306,1251 The findings from different exercise or stress imaging modalities (echocardiography versus nuclear MPI) can be even more difficult to compare, such that clinicians should use the same imaging modality over time whenever possible. Despite these concerns, significant changes in risk category (such as shifting to a lower- or higher-risk patient subset) may be used to guide interpretabil- ity of interval change in repeat testing,306,333 and the presence of significant interval change can alter risk assessment. For example, in the ACME (Angioplasty Compared to Medicine) trial, patients whose exercise nuclear MPI normalized after 6 months of randomized treatment had an improved survival Figure 15. Incidence of cardiac death or nonfatal MI during follow-up after a nor- mal stress MPI. Adapted with permission from Hachamovitch et al.327 MI indicates myocardial infarction; MPI, myocardial perfusion imaging. Fihn et al Stable Ischemic Heart Disease: Full Text e433 rate (92%) compared with those with persistent ischemia (82%, P50.02).333 The ongoing technical evolution within imaging modalities is, in part, aimed at minimizing intraob- server, interobserver, and intertest variability. 6.3.7. Future Developments Numerous opportunities to improve the diagnosis and man- agement of SIHD remain. Large registries have the potential to improve the diagnosis of IHD and to assess risk according to clinical information and results from noninvasive testing. Risk-assessment strategies from older databases should be updated with modern information and statistical techniques. Technical development across all cardiac imaging modalities continues to evolve rapidly, often outpacing the ability to perform rigorous clinical validation and application. Current and anticipated technical developments of CT scanners and software are intended to improve the spatial and temporal resolution of cardiac CT images while reducing the radiation dose received from a typical examination. They include wider detector arrays that allow higher numbers of simultaneously acquired image slices, faster x-ray tube rotation times, and the use of alternative image reconstruction techniques that target image noise, all of which could improve the diagnostic value of CCTA in currently challenging scenarios, such as calcified coronary arteries and coronary stents. The improvement also will foster the study and clinical use of newer applications of cardiac CT, such as coronary plaque characterization, late enhancement imaging for the detection of myocardial scar, and MPI to detect myocardial ischemia.1252 Efforts currently under way to obtain perfusion information from CCTA images are promising,196 201 with one report also calculating FFR with CCTA.195 Moreover, plaque quantification soft- ware is in development and could further guide accurate detection of atherosclerotic disease burden.1253 Several new developments in stress nuclear MPI have occurred, including new radioisotopes: 1) an F18 PET perfu- sion agent (in Phase III trials), which will allow exercise PET I-beta-methyl-iodophenylpentadecanoic acid SPECT, with the unique ability to document metabolic alterations representing prior ischemic episodes (ie, ischemic I-labeled meta-iodobenzylguanidine SPECT, which could be helpful for assessment of arrhythmic risk in SIHD patients.1254 Several new SPECT cameras also have been introduced into the marketplace and offer the opportunity for improved image quality within a substantially shorter time period and with a lower radiation dose.1255,1256 Several studies have correlated atherosclerotic plaque char- acteristics with the extent of ischemic myocardium by stress nuclear MPI.202 206,215 Finally, the diagnostic and prognostic value of PET flow reserve data is currently under intense Echocardiography, being the most portable and widely available stress imaging technique, has developed novel methods that are promising in the assessment of SIHD patient. Speckle-tracking echocardiography provides a 2-dimensional, angle-independent, real-time evaluation of myocardial strain and has been shown to detect myocardial ischemia incremental to wall motion analysis.1258,1259 Recent reports of contrast echocardiography MPI during vasodilating stress indicate that it is a potentially robust and clinically viable tool in detection of CAD.1260 Finally, 3-dimensional techniques can provide an improved assessment of cardiac size and function in patients with SIHD. Increasing recognition of the ability of CMR to accurately assess abnormal myocardial physiology of CAD by combined imaging of rest and stress ventricular function, perfusion, and myocardial viability is expected to increase its use in SIHD.172,1261,1262 With rapid data acquisition by parallel imaging, real-time cine, or sub-second single-shot imaging methods, a diagnostically adequate CMR can be obtained without the need for patient breath-holding or ECG gat- ing.1263 A routine CMR assessment of CAD can be achieved in ,30 minutes. These developments likely will improve diagnostic consistency and patient throughput of CMR. CMR myocardial perfusion and LGE imaging for ischemia and scar, respectively, have improved image quality at 3.0T field strength compared to 1.5T and have been shown to improve diagnostic accuracy in detecting CAD.1264 Whole-heart 3-dimensional coronary magnetic resonance angiography with navigator respiratory-gating has shown promising pilot results and is being evaluated in clinical trials.1265,1266 Further studies on lipid management are warranted to ascertain the optimal drug regimens for patients with SIHD. Questions remain as to the optimal dose of statins and the effectiveness of combining lipid-lowering medications. In addition, studies that establish the effectiveness of CABG in comparison with contemporary GDMT are necessary, as are studies that better define the relative benefits of different revascularization techniques (Figure 13). Presidents and Staff American College of Cardiology Foundation William A. Zoghbi, MD, FACC, President Thomas E. 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