However, the performance of these same tools in predicting short-term and long-term risk for coronary mortality and coronary events might vary in patients with known SIHD as compared with patients without known disease who present with chest pain syndromes that might or might not represent angina. Although mortality and morbidity rates intuitively might be considered to be higher in patients with documented as opposed to suspected CAD, evidence-based medical management, including adherence to appropriate lifestyle changes, and possibly appropriate revas- cularization in patients with ACS or patients identified as high risk with worsening clinical status or persistent symp- toms despite GDMT, might explain the generally low mor- tality risk that has been found in several studies of patients with established SIHD.57,58,366,1216,1217 The incidence of ad- verse events during longitudinal follow-up of SIHD has declined and can be expected to vary with evolving medical management and with accruing information about the out- comes of revascularization.295,898,1163,1217 1219 Although data on serial testing are limited, one approach to identifying candidates for follow-up testing is to apply prognostic scores for detection of patients with SIHD who are at high risk of MACE. The findings of studies that have examined the prognostic value of testing among patients with known stable CAD who are receiving contemporary GDMT306,1220 1223 could provide clues for identifying candi- dates and appropriate intervals for follow-up testing. In the TIBET (Total Ischemic Burden European Trial) study group, which comprised 682 patients with stable angina and positive exercise ECG tests, adverse outcome was predicted by time to ischemia during exercise, prior infarction or prior CABG, ECG evidence for LV hypertrophy, and LV enlargement by echocardiography.58 Easily available clinical characteristics have been the strongest predictors of risk during follow-up of patients with SIHD in other studies.


In the TIBET (Total Ischemic Burden European Trial) study group, which comprised 682 patients with stable angina and positive exercise ECG tests, adverse outcome was predicted by time to ischemia during exercise, prior infarction or prior CABG, ECG evidence for LV hypertrophy, and LV enlargement by echocardiography.58 Easily available clinical characteristics have been the strongest predictors of risk during follow-up of patients with SIHD in other studies. The Euro Heart Survey found that a score based on the cumulative presence of comorbidity, diabetes mellitus, severity of angina, onset of recurrent symptoms ,6 months previously, abnormal ven- tricular function, and resting ECG repolarization abnormali- ties was associated with an increase in the 1-year risk of death or nonfatal infarction that ranged nearly 100-fold (from 0.5% to 47%) among .3000 outpatients.57 The ACTION (A Coronary Disease Trial Investigating Outcome with Nifedi- pine Gastrointestinal Therapeutic System) trial derived a clinical risk score that separated 5-year risk of death, MI, or stroke from 4% to 35% in .7300 patients with stable angina on the basis of commonly available clinical variables. In order of decreasing importance, the variables included age, LVEF, smoking, white blood cell count, presence of diabetes mellitus, casual (any time of day without regard to time since the last meal) blood glucose concentration, creatinine, prior stroke, frequent angina, findings at coronary angiography, lipid-lowering treatment, QT interval on the resting ECG, systolic hypertension, number of drugs used for angina, prior infarction, and sex.1216 Because the populations enrolled in these studies varied and the results have not been indepen- dently validated, additional prospective studies of patients with established SIHD are required to establish appropriate follow-up evaluation strategies and to establish efficient time intervals for evaluation in stable patients.307,320,1223,1224 6.2.


In order of decreasing importance, the variables included age, LVEF, smoking, white blood cell count, presence of diabetes mellitus, casual (any time of day without regard to time since the last meal) blood glucose concentration, creatinine, prior stroke, frequent angina, findings at coronary angiography, lipid-lowering treatment, QT interval on the resting ECG, systolic hypertension, number of drugs used for angina, prior infarction, and sex.1216 Because the populations enrolled in these studies varied and the results have not been indepen- dently validated, additional prospective studies of patients with established SIHD are required to establish appropriate follow-up evaluation strategies and to establish efficient time intervals for evaluation in stable patients.307,320,1223,1224 6.2. Follow-Up of Patients With SIHD Standard risk assessment tools that have been developed from clinical and laboratory evaluation of ambulatory populations with suspected CAD, as discussed in detail in Section 2 of this guideline, include patients who have noncardiac causes of presenting symptoms. Estimates of the likelihood of future cardiac events using the Framingham score,508,1225 which was Fihn et al Stable Ischemic Heart Disease: Full Text e427 derived from populations that included large numbers of low-risk individuals without disease in their low-risk subsets, are not generally useful when applied to patients with known SIHD. In fact, prediction of risk for coronary mortality and coronary events during short-term and long-term follow-up of patients with SIHD differs from risk stratification in less- ascertained populations with chest pain syndromes. Although mortality and morbidity rates intuitively might be considered to be higher in patients with documented as opposed to suspected IHD, several circumstances serve to confound this assumption. Patients at highest risk, for example, are often identified and aggressively treated during the course of ACS or during initial risk assessment of chest pain.


Patients at highest risk, for example, are often identified and aggressively treated during the course of ACS or during initial risk assessment of chest pain. After being treated, asymptomatic patients are typically at low risk for adverse events. Moreover, patients with recognized SIHD could be more likely to receive and adhere to effective therapies than are those whose disease has not been docu- mented. Finally, patients who have been stable for long periods of time could be less prone to development of ACS than are newly ascertained patients with SIHD. Thus, evidence-based medical management, including adherence to appropriate lifestyle changes and possibly appropriate revas- cularization in patients with ACS or patients identified as high risk with worsening clinical status or persistent symp- toms despite GDMT, could explain the generally low mor- tality risk that has been found in several studies of patients with established but stable SIHD.57,58,366,1216,1217 Moreover, large trials conducted during the past decade have shown a declining mortality rate among patients with established SIHD.295,898,1163,1217,1218 Accordingly, risk could change with advances in therapy and patient management, and these advances could alter risk-prediction models. A key component in following up patients with SIHD is to systematically and reproducibly monitor their symptoms and functional status. This should be done, at a minimum, yearly and ideally at each visit. Even though the CCS classification system is the most common metric with which to quantify patients symptoms and function, as noted previously, it is limited by being from the physician s perspective rather than the patient s. Moreover, it has limitations in its reproducibil- ity and interrater reliability.


Even though the CCS classification system is the most common metric with which to quantify patients symptoms and function, as noted previously, it is limited by being from the physician s perspective rather than the patient s. Moreover, it has limitations in its reproducibil- ity and interrater reliability. To obtain a valid, reliable, reproducible, and sensitive assessment of patients symp- toms, function, and quality of life from patients perspectives, the SAQ can be used.435,1226 The SAQ is a 19-item, self- reported questionnaire that takes approximately 5 minutes for most patients to complete and explicitly quantifies patients angina frequency, recent changes in their angina, their phys- ical limitations due to angina, their satisfaction with treat- ment, and their perceptions of how their angina limits their quality of life. Scores on the SAQ have been shown to be associated with subsequent survival. ACS admissions and costs246,247,1227 can be integrated into prognostic models to identify patients warranting more aggressive treatment be- cause of an adverse prognosis. In the CADENCE (Coronary Artery Disease in General Practice) study, conducted in 207 primary care clinics throughout Australia,1228 Beltrame and colleagues found wide variation in anginal symptoms accord- ing to the SAQ. Routine use of the SAQ has been endorsed as a performance measure of quality in SIHD.407,436 6.2.1. Focused Follow-Up Visit: Frequency Patients with SIHD should receive regular follow-up to monitor symptoms and progression or complications of dis- ease. Regular visits with a healthcare provider are also necessary to evaluate patients adherence to and effectiveness of therapy as well as occurrence of any adverse effects. Although there are scant data on which to base a definitive recommendation, the writing committee recommends a clin- ical follow-up evaluation every 4 to 12 months.


Although there are scant data on which to base a definitive recommendation, the writing committee recommends a clin- ical follow-up evaluation every 4 to 12 months. A more precise interval cannot be recommended because many fac- tors influence the length of the follow-up period, including sharing of care by family physicians, internists, and cardiol- ogists, which will vary with regional practice patterns, patient preference, and physician availability. During the first year of therapy, evaluations every 4 to 6 months are recommended. After the first year of therapy, evaluations every 6 to 12 months are recommended if the patient is stable and reliable enough to call or make an appointment when symptoms or functional capacity become worse. Limited data from obser- vational studies indicate that outcomes might be better for patients who receive follow-up from a cardiologist.1229,1230 When patients are managed jointly by their primary care physician and cardiologist, effective communication between physicians is essential. This ultimately will be facilitated by effective implementation of accessible electronic medical records. Periodic office visits can be supplemented by tele- phone, e-mail, or other types of contact between the patient and the healthcare team. 6.2.2. Focused Follow-Up Visit: Interval History and Coexisting Conditions Although follow-up of patients with SIHD often is focused on periodic testing, the most crucial element is a careful interval history. Key elements of the history are: Changes in physical activity or symptoms; Response to therapy, adverse effects, and adherence to recommendations; and Development of relevant, new chronic conditions or changes in existing conditions. Symptomatic change and decreasing functional capacity are important markers for increased risk in patients with SIHD, particularly with increasing age and additional comor- bidities. The evaluation of symptoms should be detailed and directed, as many patients are reluctant to volunteer such information.


The evaluation of symptoms should be detailed and directed, as many patients are reluctant to volunteer such information. It should be noted whether patients have reduced their activity, perhaps in an effort to ameliorate anginal symptoms or as a symptom of ventricular dysfunction. The adverse prognostic importance of frequent, typical angina in patients with SIHD is evident in both older and newer studies of risk.57,126,127,1231,1232 Motivation and compliance with risk- reduction measures should be carefully assessed. In particu- lar, assistance with smoking cessation by means of a struc- tured program might be necessary for some patients. Careful attention must be paid to concomitant conditions, such as hypertension, diabetes mellitus, dyslipidemia, heart failure, and depression. 6.2.3. Focused Follow-Up Visit: Physical Examination The physical examination should be directed according to the patient s history. Every patient should have weight, BP, and heart rate measured. BMI and waist circumference can provide signs of additional risk. Signs of heart failure, such as elevated jugular venous pressure, hepatojugular reflux, pul- monary crackles, new murmurs or gallops, or edema, should be sought. The vascular examination should identify any change in peripheral pulses or new bruits. Coexistence of SIHD with extracranial carotid disease makes palpation and auscultation of the carotid arteries particularly important, and examination of the abdomen should include special attention to bruits or abnormally prominent pulsations of the abdomi- nal aorta. 6.2.4. Focused Follow-Up Visit: Resting 12-Lead ECG An ECG is necessary when there is a change in anginal pattern, symptoms or findings suggestive of a dysrhythmia or conduction abnormality, and near or frank syncope.


Focused Follow-Up Visit: Resting 12-Lead ECG An ECG is necessary when there is a change in anginal pattern, symptoms or findings suggestive of a dysrhythmia or conduction abnormality, and near or frank syncope. It is important to recognize that periodic recording of the standard 12-lead ECG has clinical value that is independent of diag- nostic and prognostic content: It provides a baseline wave- form against which tracings taken during symptoms reason- ably can be compared. Because many patients with SIHD have resting repolarization abnormalities, absence of a timely tracing for comparison with a tracing taken during atypical symptoms can lead to overdiagnosis of acute ische- mia.1233,1234 Conversely, repolarization abnormalities dur- ing symptoms that might be new or significantly more marked can also be consistent with old disease and lead to underdiagnosis or undertreatment of unstable disease.1235 New repolarization abnormalities during serial study have been shown to predict cardiovascular events during the longitudinal study of hypertensive patients in the Framing- ham Heart Study.318 A study of hypertensive patients that included a subgroup with established SIHD also demon- strated an increased risk of cardiovascular endpoints after the development of new repolarization changes during serial evaluation.318,1236 Although there are no prospective randomized data demonstrating that intervention based on routine, periodic evaluation of the ECG alone will alter outcomes in patients with SIHD, pending such evidence, the clinical value of a change in the resting ECG is widely accepted. In patients with established SIHD, a change in a periodically obtained ECG can be the only evidence of intercurrent silent infarction, inadequately treated hyper- tension, or complex arrhythmia that would modify treat- ment.


In patients with established SIHD, a change in a periodically obtained ECG can be the only evidence of intercurrent silent infarction, inadequately treated hyper- tension, or complex arrhythmia that would modify treat- ment. The timing between routine recordings of the 12- lead ECG that would be required and adequate to accomplish these purposes has not been established, but a consensus recommendation based on expert opinion and common practice would be not greater than once yearly for stable patients with SIHD, as well as at the time of any clinical change. 6.2.5. Focused Follow-Up Visit: Laboratory Examination Patients not known to have diabetes mellitus should have a fasting blood glucose measurement every 3 years to detect new-onset diabetes mellitus, and those with established dia- betes mellitus should have glycosylated hemoglobin mea- sured at least annually to assess glycemic control. A lipid profile should be obtained as clinically warranted. Long-term studies (up to 7 years) demonstrate sustained benefit from continued therapy.18,318 Measurement of creatinine kinase also could be appropriate at these times. In circumstances in which the patient is not concurrently followed up by a primary care physician, measurements of hemoglobin, thy- roid function, serum electrolytes, and renal function should be obtained annually, or sooner when prompted by a change in symptoms or signs. 6.3. Noninvasive Testing in Known SIHD For any patients with known SIHD who have recurrent but stable symptoms after having been symptom free for a period of time on GDMT or after revascularization and who do not fall into any of the categories listed in the previous paragraph, the concepts underlying the recommendations for Noninva- sive Testing for Diagnosis of IHD from Section 2.2 gener- ally apply, with the modifications and special consideration discussed below. 6.3.1.


Noninvasive Testing in Known SIHD For any patients with known SIHD who have recurrent but stable symptoms after having been symptom free for a period of time on GDMT or after revascularization and who do not fall into any of the categories listed in the previous paragraph, the concepts underlying the recommendations for Noninva- sive Testing for Diagnosis of IHD from Section 2.2 gener- ally apply, with the modifications and special consideration discussed below. 6.3.1. Follow-Up Noninvasive Testing in Patients With Known SIHD: New, Recurrent, or Worsening Symptoms Not Consistent With Unstable Angina: Recommendations See Table 20 for a summary of recommendations from this section. 6.3.1.1. Patients Able to Exercise Class I 1. Standard exercise ECG testing is recommended in patients with known SIHD who have new or wors- ening symptoms not consistent with UA and who have a) at least moderate physical functioning and no disabling comorbidity and b) an interpretable ECG.114,145 147 (Level of Evidence: B) 2. Exercise with nuclear MPI or echocardiography is rec- ommended in patients with known SIHD who have new or worsening symptoms not consistent with UA and who have a) at least moderate physical functioning or no disabling comorbidity but b) an uninterpretable ECG.172,276,278,284,306,313,314,320,324,327 329,1237 1240 (Level of Evidence: B) Class IIa 1. Exercise with nuclear MPI or echocardiography is reasonable in patients with known SIHD who have new or worsening symptoms not consistent with UA and who have a) at least moderate physical function- ing and no disabling comorbidity, b) previously required imaging with exercise stress, or c) known multivessel disease or high risk for multivessel dis- ease.1241,1242 (Level of Evidence: B) Class III: No Benefit 1.


Exercise with nuclear MPI or echocardiography is reasonable in patients with known SIHD who have new or worsening symptoms not consistent with UA and who have a) at least moderate physical function- ing and no disabling comorbidity, b) previously required imaging with exercise stress, or c) known multivessel disease or high risk for multivessel dis- ease.1241,1242 (Level of Evidence: B) Class III: No Benefit 1. Pharmacological stress imaging with nuclear MPI, echocardiography, or CMR is not recommended in patients with known SIHD who have new or worsening symptoms not consistent with UA and who are capable of at least moderate physical Fihn et al Stable Ischemic Heart Disease: Full Text e429 functioning or have no disabling comorbidity.333 (Level of Evidence: C) 6.3.1.2. Patients Unable to Exercise Class I 1. Pharmacological stress imaging with nuclear MPI or echocardiography is recommended in patients with known SIHD who have new or worsening symptoms not consistent with UA and who are incapable of at least moderate physical function- ing or have disabling comorbidity.148 150,152 156 (Level of Evidence: B) Class IIa 1. Pharmacological stress imaging with CMR is rea- sonable in patients with known SIHD who have new or worsening symptoms not consistent with UA and who are incapable of at least moderate physical functioning or have disabling comorbidity.280,281,283 (Level of Evidence: B) Class III: No Benefit 1. Standard exercise ECG testing should not be per- formed in patients with known SIHD who have new or worsening symptoms not consistent with UA and who a) are incapable of at least moderate physical functioning or have disabling comorbidity or b) have an uninterpretable ECG. (Level of Evidence: C) 6.3.1.3. Irrespective of Ability to Exercise Class IIb 1.


(Level of Evidence: C) 6.3.1.3. Irrespective of Ability to Exercise Class IIb 1. CCTA for assessment of patency of CABG or of coronary stents 3 mm or larger in diameter might be reasonable in patients with known SIHD who have new or worsening symptoms not consistent with UA, irrespective of ability to exercise.1244 1248 (Level of Evidence: B) 2. CCTA might be reasonable in patients with known SIHD who have new or worsening symptoms not consistent with UA, irrespective of ability to exercise, in the absence of known moderate or severe calcifi- Table 20.


CCTA might be reasonable in patients with known SIHD who have new or worsening symptoms not consistent with UA, irrespective of ability to exercise, in the absence of known moderate or severe calcifi- Table 20. Follow-Up Noninvasive Testing in Patients With Known SIHD: New, Recurrent, or Worsening Symptoms Not Consistent With UA Test Exercise Status ECG Interpretable COR LOE References Additional Considerations Able Unable Yes No Patients able to exercise* Exercise ECG X X I B (114, 145 147) Exercise with nuclear MPI or Echo X X I B (172, 276, 278, 284, 306, Exercise with nuclear MPI or Echo X Any IIa B (1241, 1242) Prior requirement for imaging with exercise Known or at high risk for multivessel disease Pharmacological stress nuclear MPI/Echo/CMR X X III: No Benefit C (333) Patients unable to exercise Pharmacological stress nuclear MPI or Echo X Any I B (148 150, 152 156) Pharmacological stress CMR X Any IIa B (280, 281, 283) Exercise ECG X X III: No Benefit C N/A Irrespective of ability to exercise CCTA Any Any IIb B (1244 1248) Patency of CABG or coronary stent $3 mm diameter CCTA Any Any IIb B (158, 161, 1244) In the absence of known moderate or severe calcification and intent to assess coronary stent ,3 mm in diameter CCTA Any Any III: No Benefit B (1244 1248) Known moderate or severe native coronary calcification or assessment of coronary stent ,3 mm in diameter in patients who have new or worsening symptoms not consistent with UA *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.


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, cardiac magnetic resonance; COR, class of recommendation; ECG, electrocardiogram; Echo, echocardiography; LOE, level of evidence; MPI, myocardial perfusion imaging; N/A, not available; SIHD, stable ischemic heart disease; and UA, unstable angina. cation or if the CCTA is intended to assess coronary stents less than 3 mm in diameter.158,161,1244 (Level of Evidence: B) Class III: No Benefit 1. CCTA should not be performed for assessment of native coronary arteries with known moderate or severe calcification or with coronary stents less than 3 mm in diameter in patients with known SIHD who have new or worsening symptoms not consistent with UA, irrespective of ability to exercise.1244 1248 (Level of Evidence: B) See Online Data Supplement 1 for additional data on nonin- vasive testing in known SIHD: recurrent or worsening symptoms. Strategies for the selection and use of noninvasive testing in the evaluation of new or worsening symptoms in patients with documented SIHD are similar to those in suspected SIHD. As always, in patients with interpretable rest ECGs who are capable of exercise, treadmill exercise ECG testing remains the first choice. Whenever possible, initial and follow-up testing should be performed with the same stress and imaging techniques so that any interval change can be attributed more reliably to alterations in clinical status rather than mere differences in technique. Loss of the ability to exercise on follow-up testing, in and of itself, suggests deterioration in functional and clinical status. In general, the diagnostic accuracy of stress testing is similar in patients with and without known SIHD (Section 2.2.3).


In general, the diagnostic accuracy of stress testing is similar in patients with and without known SIHD (Section 2.2.3). A few meta-analyses examining the effect of prior MI on diagnostic accuracy have found that the specificity of exercise ECG was higher in mixed popula- tions,145 whereas the diagnostic performance of exercise echocardiography was reduced. In contrast, the specificity of exercise SPECT was increased because of the predictive value of total stress perfusion abnormalities, which in- cludes both the risk of ischemia plus infarcted myocardi- um.91 Although CMR LGE imaging detects MI, current evidence indicates that assessment of myocardial ischemia provides incremental diagnostic1249 and prognostic value above LGE detection of infarction284 in patients with or without known SIHD. In contrast to stress testing, the diagnostic value of CCTA differs in patients with and without known CAD. Limitations of image quality relating to coronary calcifi- cation, coronary stents, or vascular clips can reduce diagnostic accuracy, and revascularization also affects results. The large caliber of venous conduits facilitates the assessment of patients who have undergone CABG with CCTA and has sensitivities of 89% to 98% and specifici- ties of 89% to 97% for the identification of .50% diameter stenoses in grafts on invasive coronary angiog- raphy.1244 1246 The accurate evaluation of coronary stents with CCTA depends on the material and diameter of the stent, with image artifacts related to the stents metallic structure preventing assessment of 9% to 11% of stents.1247,1248 Typically, stents .3 mm in diameter can be assessed,1248 with sensitivities for detecting a .50% di- ameter in-stent restenosis on invasive coronary angiogra- phy of 86% to 94% and specificities of 91% to 93%. 6.3.2. Noninvasive Testing in Known SIHD Asymptomatic (or Stable Symptoms): Recommendations See Table 21 for a summary of recommendations from this section. Table 21.


Noninvasive Testing in Known SIHD Asymptomatic (or Stable Symptoms): Recommendations See Table 21 for a summary of recommendations from this section. Table 21. Noninvasive Testing in Known SIHD: Asymptomatic (or Stable Symptoms) Test Exercise Status ECG Interpretable Pretest Probability of Ischemia COR LOE References Additional Considerations Able* Unable Yes No Exercise or pharmacological stress with nuclear MPI, Echo, or CMR at $2-y intervals X X Prior evidence of silent ischemia or high risk for recurrent cardiac event. Meets criteria listed in additional considerations. IIa C (10, 12, 15) a) Unable to exercise to adequate workload or b) Uninterpretable ECG or c) History of incomplete coronary revascularization Exercise ECG at $1-y intervals X X Any IIb C N/A a) Prior evidence of silent ischemia OR b) At high risk for recurrent cardiac event Exercise ECG X X No prior evidence of silent ischemia and not at high risk of recurrent cardiac event. 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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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).


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. Arend, Jr. Esq, CAE, Interim Chief Staff Officer William J. Oetgen, MD, MBA, FACC, Senior Vice President, Science and Quality Charlene L. May, Senior Director, Science and Clinical Policy Erin A. Barrett, MPS, Senior Specialist, Science and Clinical Policy American College of Cardiology Foundation/American Heart Association Lisa Bradfield, CAE, Director, Science and Clinical Policy Maria Koinis, Specialist, Science and Clinical Policy Sue Keller, BSN, MPH, Senior Specialist, Evidence-Based Medicine American Heart Association Gordon F. Tomaselli, MD, FAHA, President Nancy Brown, Chief Executive Officer Rose Marie Robertson, MD, FAHA, Chief Science Officer Gayle R. Whitman, PhD, RN, FAHA, FAAN, Senior Vice President, Office of Science Operations Judy L. Bezanson, DSN, RN, CNS-MS, FAHA, Science and Medicine Advisor, Office of Science Operations References 1. ACCF/AHA Task Force on Practice Guidelines. Methodology Manual and Policies From the ACCF/AHA Task Force on Practice Guidelines. 2012. Availableat:http://assets.cardiosource.com/Methodology_Manual_for_ACC_ AHA_Writing_Committees.pdf and http://my.americanheart.org/idc/groups/ ahamah-public/@wcm/sop/documents/downloadable/ucm_319826.pdf. Accessed May 16, 2012. 2. Antman EM, Hand M, Armstrong PW, et al. 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2008;117:296 329. 3. Kushner FG, Hand M, Smith SC Jr, et al.


3. Kushner FG, Hand M, Smith SC Jr, et al. 2009 focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutane- ous coronary intervention (updating the 2005 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2009;120:2271 306. 4. Jneid H, Anderson JL, Wright RS, et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/ non ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2012;126:875 910. 4a. Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 guidelines for the man- agement of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. Cir- culation. 2011;123:e426 579. 5. Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2010;122: e584 636. 6. Braunwald E, Mark D, Jones R, et al. Unstable Angina: Diagnosis and Management. Clinical Practice Guideline Number 10. Rockville, MD: Agency for Healthcare Policy and Research and the National Heart, Lung, and Blood Institute, Public Health Service, US Department of Health and Human Services: 1994. 7. Gibbons RJ, Abrams J, Chatterjee K, et al.


Rockville, MD: Agency for Healthcare Policy and Research and the National Heart, Lung, and Blood Institute, Public Health Service, US Department of Health and Human Services: 1994. 7. Gibbons RJ, Abrams J, Chatterjee K, et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina summary article: a report of the American College of Cardiology/ American Heart Association Task Force on practice guidelines (Com- mittee on the Management of Patients With Chronic Stable Angina). Circulation. 2003;107:149 58. 8. Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011;124:2458 73. 9. Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124:e652 735. 10. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124:e574 651. 11. Patel MR, Spertus JA, Brindis RG, et al. ACCF proposed method for evaluating the appropriateness of cardiovascular imaging. J Am Coll Cardiol. 2005;46:1606 13. 12. Hendel RC, Berman DS, Di Carli MF, et al.


12. Hendel RC, Berman DS, Di Carli MF, et al. 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 Echocardiogra- phy, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine. Circulation. 2009;119:e561 87. 13. Hendel RC, Patel MR, Kramer CM, et al. ACCF/ACR/SCCT/SCMR/ ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging: a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group, American College of Radiology, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Res- onance, American Society of Nuclear Cardiology, North American Society for Cardiac Imaging, Society for Cardiovascular Angiography and Interventions, and Society of Interventional Radiology. J Am Coll Cardiol. 2006;48:1475 97. 14. Taylor AJ, Cerqueira M, Hodgson JM, et al. ACCF/SCCT/ACR/AHA/ ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Nuclear Cardiology, the North American Society for Car- diovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. Circulation. 2010;122:e525 55. 15. Douglas PS, Garcia MJ, Haines DE, et al.


2010;122:e525 55. 15. Douglas PS, Garcia MJ, Haines DE, et al. ACCF/ASE/AHA/ASNC/ HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 appropriate use criteria for echocardiography: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Res- onance. J Am Coll Cardiol. 2011;57:1126 66. 16. Antman EM, Peterson ED. Tools for guiding clinical practice from the american heart association and the american college of cardiology: what are they and how should clinicians use them? Circulation. 2009; 119:1180 5. 17. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206 52. 18. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circu- lation. 2002;106:3143 421. 19. Fraker TD Jr, Fihn SD, Gibbons RJ, et al. 2007 chronic angina focused update of the ACC/AHA 2002 guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to Develop the Focused Update of the 2002 Guidelines for the Management of Patients with Chronic Stable Angina. Circulation. 2007;116:2762 72. 20. Bonow RO, Carabello BA, Chatterjee K, et al.


2007;116:2762 72. 20. Bonow RO, Carabello BA, Chatterjee K, et al. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease). Circu- lation. 2008;118:e523 661. 21. Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incor- porated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. [published correction appears in Circulation. 2010;121:e258]. Circulation. 2009;119: e391 479. 22. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarc- tion: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myo- cardial infarction). Circulation. 2004;110:e82 292. 23. Deleted in proof. 24. Grundy SM, Cleeman JI, Merz CNB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227 39. Fihn et al Stable Ischemic Heart Disease: Full Text e435 25. Balady GJ, Ades PA, Bittner VA, et al. Referral, enrollment, and delivery of cardiac rehabilitation/secondary prevention programs at clinical centers and beyond: a presidential advisory from the American Heart Association. Circulation. 2011;124:2951 60. 26. Mensah GA, Brown DW. An overview of cardiovascular disease burden in the United States. Health Aff (Millwood). 2007;26:38 48. 27. Lloyd-Jones D, Adams RJ, Brown TM, et al.


2007;26:38 48. 27. Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke statistics 2010 update: a report from the American Heart Association. Circulation. 2010;121:e46 e215. 28. Ford ES, Capewell S. Coronary heart disease mortality among young adults in the U.S. from 1980 through 2002: concealed leveling of mortality rates. J Am Coll Cardiol. 2007;50:2128 32. 29. Murphy SL, Xu JQ, Kochanek KD. Deaths: Preliminary Data for 2010. National Vital Statistics Reports. 2012;60. 30. National Heart, Lung, and Blood Institute. 2006. Incidence and Prev- alence: 2006 Chart Book on Cardiovascular and Lung Diseases. Bethesda, MD: National Institutes of Health. 2006. Available at: http:// www.nhlbi.nih.gov/resources/docs/06_ip_chtbk.pdf. Accessed January 6, 2012. 31. Hlatky MA, Rogers WJ, Johnstone I, et al. Medical care costs and quality of life after randomization to coronary angioplasty or coronary bypass surgery. Bypass Angioplasty Revascularization Investigation (BARI) Investigators. N Engl J Med. 1997;336:92 9. 32. Maddox TM, Reid KJ, Spertus JA, et al. Angina at 1 year after myocardial infarction: prevalence and associated findings. Arch Intern Med. 2008;168:1310 6. 33. Hemingway H, McCallum A, Shipley M, et al. Incidence and prog- nostic implications of stable angina pectoris among women and men. JAMA. 2006;295:1404 11. 34. Elveback LR, Connolly DC. Coronary heart disease in residents of Rochester, Minnesota. V. Prognosis of patients with coronary heart disease based on initial manifestation. Mayo Clin Proc. 1985;60: 305 11. 35. Kannel WB, Feinleib M. Natural history of angina pectoris in the Framingham study. Prognosis and survival. Am J Cardiol. 1972;29: 154 63. 36. Rumsfeld JS, Magid DJ, Plomondon ME, et al. Health-related quality of life after percutaneous coronary intervention versus coronary bypass surgery in high-risk patients with medically refractory ischemia. J Am Coll Cardiol. 2003;41:1732 8. 37. Rumsfeld JS, MaWhinney S, McCarthy M Jr, et al.


37. Rumsfeld JS, MaWhinney S, McCarthy M Jr, et al. Health-related quality of life as a predictor of mortality following coronary artery bypass graft surgery. Participants of the Department of Veterans Affairs Cooperative Study Group on Processes, Structures, and Outcomes of Care in Cardiac Surgery. JAMA. 1999;281:1298 303. 38. Wiest FC, Bryson CL, Burman M, et al. Suboptimal pharmacothera- peutic management of chronic stable angina in the primary care setting. Am J Med. 2004;117:234 41. 39. Medicare & Medicaid Statistical Supplement. Centers for Medicare and Medicaid Services. 2006. Available at: http://www.cms.hhs.gov/ MedicareMedicaidStatSupp/. Accessed September 12, 2008. 40. Riley RF, Don CW, Powell W, et al. Trends in Coronary Revascular- ization in the United States from 2001 2009: recent declines in per- cutaneous coronary intervention volumes. Circ Cardiovasc Qual Outcomes. 2011;4:193 7. 41. Schappert SM, Burt CW. Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 2001 02. Vital Health Stat 13. 2006;1 66. 42. Javitz HS, Ward MM, Watson JB, et al. Cost of illness of chronic angina. Am J Manag Care. 2004;10:S358 S369. 43. Shaw LJ, Merz CNB, Pepine CJ, et al. The economic burden of angina in women with suspected ischemic heart disease: results from the National Institutes of Health National Heart, Lung, and Blood Insti- tute sponsored Women s Ischemia Syndrome Evaluation. Circu- lation. 2006;114:894 904. 44. Frosch DL, Kaplan RM. Shared decision making in clinical medicine: past research and future directions. Am J Prev Med. 1999;17:285 94. 45. Kasper JF, Mulley AG Jr, Wennberg JE. Developing shared decision- making programs to improve the quality of health care. QRB Qual Rev Bull. 1992;18:183 90. 46. Krumholz HM. Informed consent to promote patient-centered care. JAMA. 2010;303:1190 1. 47. Fox K, Garcia MAA, Ardissino D, et al.


2010;303:1190 1. 47. Fox K, Garcia MAA, Ardissino D, et al. Guidelines on the management of stable angina pectoris: executive summary: the Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J. 2006;27:1341 81. 48. Gibbons RJ, Balady GJ, Bricker JT, et al. 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). Circulation. 2002;106:1883 92. 49. Wijns W, Kolh P, Danchin N, et al. Guidelines on myocardial revas- cularization. Eur Heart J. 2010;31:2501 55. 50. Braunwald E. Unstable angina. A classification. Circulation. 1989;80: 410 4. 51. Critchfield TS, Kollins SH. Temporal discounting: basic research and the analysis of socially important behavior. J Appl Behav Anal. 2001; 34:101 22. 52. Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med. 1979;300: 1350 8. 53. Deleted in proof. 54. Pepine CJ, Balaban RS, Bonow RO, et al. Women s Ischemic Syndrome Evaluation: current status and future research directions: report of the National Heart, Lung and Blood Institute workshop: October 2 4, 2002: Section 1: diagnosis of stable ischemia and ische- mic heart disease. Circulation. 2004;109:e44 e46. 55. Califf RM, Armstrong PW, Carver JR, et al. 27th Bethesda Con- ference: matching the intensity of risk factor management with the hazard for coronary disease events. Task Force 5. Stratification of patients into high, medium and low risk subgroups for purposes of risk factor management. J Am Coll Cardiol. 1996;27:1007 19. 56. Chatterjee K. Recognition and management of patients with stable angina pectoris. In: Goldman L, Braunwald E, editors. Primary Car- diology. Philadelphia: WB Saunders; 1998:234 56. 57.


In: Goldman L, Braunwald E, editors. Primary Car- diology. Philadelphia: WB Saunders; 1998:234 56. 57. Daly CA, De Stavola B, Sendon JLL, et al. Predicting prognosis in stable angina results from the Euro heart survey of stable angina: prospective observational study. BMJ. 2006;332:262 7. 58. Daly C, Norrie J, Murdoch DL, et al. The value of routine non-invasive tests to predict clinical outcome in stable angina. Eur Heart J. 2003; 24:532 40. 59. Hammermeister KE, DeRouen TA, Dodge HT. Variables predictive of survival in patients with coronary disease. Selection by univariate and multivariate analyses from the clinical, electrocardiographic, exercise, arteriographic, and quantitative angiographic evaluations. Circulation. 1979;59:421 30. 60. Block WJ Jr, Crumpacker EL, Dry TJ, et al. Prognosis of angina pectoris; observations in 6,882 cases. J Am Med Assoc. 1952;150: 259 64. 61. Prospective randomised study of coronary artery bypass surgery in stable angina pectoris. Second interim report by the European Coronary Surgery Study Group. Lancet. 1980;2:491 5. 62. Frank CW, Weinblatt E, Shapiro S. Angina pectoris in men. Prognostic significance of selected medical factors. Circulation. 1973;47:509 17. 63. Murphy ML, Hultgren HN, Detre K, et al. Treatment of chronic stable angina. A preliminary report of survival data of the randomized Veterans Administration cooperative study. N Engl J Med. 1977;297: 621 7. 64. Proudfit WJ, Bruschke AV, MacMillan JP, et al. Fifteen year survival study of patients with obstructive coronary artery disease. Circulation. 1983;68:986 97. 65. Ruberman W, Weinblatt E, Goldberg JD, et al. Ventricular premature complexes in prognosis of angina. Circulation. 1980;61:1172 82. 66. Detre K, Peduzzi P, Murphy M, et al. Effect of bypass surgery on survival in patients in low- and high-risk subgroups delineated by the use of simple clinical variables. Circulation. 1981;63:1329 38. 67. Knochel JP, Beisel WR, Herndon EG Jr, et al.


67. Knochel JP, Beisel WR, Herndon EG Jr, et al. The renal, cardiovas- cular, hematologic and serum electrolyte abnormalities of heat stroke. Am J Med. 1961;30:299 309. 68. Hollander JE. The management of cocaine-associated myocardial is- chemia. N Engl J Med. 1995;333:1267 72. 69. McCord J, Jneid H, Hollander JE, et al. Management of cocaineasso- ciated chest pain and myocardial infarction: a scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology. Circulation. 2008;117:1897 907. 70. Pryor DB, Shaw L, Harrell FE Jr, et al. Estimating the likelihood of severe coronary artery disease. Am J Med. 1991;90:553 62. 71. Pryor DB, Shaw L, McCants CB, et al. Value of the history and physical in identifying patients at increased risk for coronary artery disease. Ann Intern Med. 1993;118:81 90. 72. Sox HC Jr, Hickam DH, Marton KI, et al. Using the patient s history to estimate the probability of coronary artery disease: a comparison of primary care and referral practices. Am J Med. 1990;89:7 14. 73. Chaitman BR, Bourassa MG, Davis K, et al. Angiographic prevalence of high-risk coronary artery disease in patient subsets (CASS). Circu- lation. 1981;64:360 7. 74. Shaw LJ, Bairey Merz CN, Pepine CJ, et al. Insights from the NHLBI- Sponsored Women s Ischemia Syndrome Evaluation (WISE) Study: Part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies. J Am Coll Cardiol. 2006;47:S4 S20. 75. Shaw LJ, Bugiardini R, Merz CNB. Women and ischemic heart dis- ease: evolving knowledge. J Am Coll Cardiol. 2009;54:1561 75. 76. Shaw LJ, Berman DS. Functional versus anatomic imaging in patients with suspected coronary artery disease. Cardiol Clin. 2009;27: 597 604. 77. Raff GL, Gallagher MJ, O Neill WW, et al.


77. Raff GL, Gallagher MJ, O Neill WW, et al. Diagnostic accuracy of noninvasive coronary angiography using 64-slice spiral computed tomography. J Am Coll Cardiol. 2005;46:552 7. 78. Fryback DG, Thornbury JR. The efficacy of diagnostic imaging. Med Decis Making. 1991;11:88 94. 79. Hlatky MA, Greenland P, Arnett DK, et al. Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association. Circulation. 2009;119:2408 16. 80. Rozanski A, Diamond GA, Berman D, et al. The declining specificity of exercise radionuclide ventriculography. N Engl J Med. 1983;309: 518 22. 81. Douglas PS. Is noninvasive testing for coronary artery disease accurate? Circulation. 1997;95:299 302. 82. Kaul S. Technical, economic, interpretative, and outcomes issues regarding utilization of cardiac imaging techniques in patients with known or suspected coronary artery disease. Am J Cardiol. 1995; 75:18D 24D. 83. Diamond GA. Reverend Bayes silent majority. An alternative factor affecting sensitivity and specificity of exercise electrocardiography. Am J Cardiol. 1986;57:1175 80. 84. Roger VL, Pellikka PA, Bell MR, et al. Sex and test verification bias. Impact on the diagnostic value of exercise echocardiography. Circu- lation. 1997;95:405 10. 85. Cecil MP, Kosinski AS, Jones MT, et al. The importance of work-up (verification) bias correction in assessing the accuracy of SPECT thallium-201 testing for the diagnosis of coronary artery disease. J Clin Epidemiol. 1996;49:735 42. 86. Miller TD, Hodge DO, Christian TF, et al. Effects of adjustment for referral bias on the sensitivity and specificity of single photon emission computed tomography for the diagnosis of coronary artery disease. Am J Med. 2002;112:290 7. 87. Diamond GA, Forrester JS, Hirsch M, et al. Application of conditional probability analysis to the clinical diagnosis of coronary artery disease. J Clin Invest. 1980;65:1210 21. 88. Goldman L, Cook EF, Mitchell N, et al.


1980;65:1210 21. 88. Goldman L, Cook EF, Mitchell N, et al. Incremental value of the exercise test for diagnosing the presence or absence of coronary artery disease. Circulation. 1982;66:945 53. 89. Melin JA, Wijns W, Vanbutsele RJ, et al. Alternative diagnostic strategies for coronary artery disease in women: demonstration of the usefulness and efficiency of probability analysis. Circulation. 1985;71: 535 42. 90. Diamond GA, Kaul S. Low diagnostic yield of elective coronary angiography. N Engl J Med. 2010;363:93 5. 91. Fleischmann KE, Hunink MG, Kuntz KM, et al. Exercise echocardi- ography or exercise SPECT imaging? A meta-analysis of diagnostic test performance. JAMA. 1998;280:913 20. 92. Cheng VY, Berman DS, Rozanski A, et al. Performance of the Tradi- tional Age, Sex, and Angina Typicality-Based Approach for Estimating Pretest Probability of Angiographically Significant Coronary Artery Disease in Patients Undergoing Coronary Computed Tomographic Angiography: results from the Multinational Coronary CT Angiography Evaluation for Clinical Outcomes: An International Mul- ticenter Registry (CONFIRM). Circulation. 2011;124:2423 32. 93. Berrington de Gonzalez A, Mahesh M, Kim K-P, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169:2071 7. 94. Gerber TC, Gibbons RJ. Weighing the risks and benefits of cardiac imaging with ionizing radiation. J Am Coll Cardiol Cardiovasc Imaging. 2010;3:528 35. 95. Berrington de Gonzalez A, Kim K-P, Smith-Bindman R, et al. Myo- cardial perfusion scans: projected population cancer risks from current levels of use in the United States. Circulation. 2010;122:2403 10. 96. Halliburton SS, Abbara S, Chen MY, et al. SCCT guidelines on radiation dose and dose-optimization strategies in cardiovascular CT. J Cardiovasc Comput Tomogr. 2011;5:198 224. 97. Cerqueira MD, Allman KC, Ficaro EP, et al. Recommendations for reducing radiation exposure in myocardial perfusion imaging. J Nucl Cardiol. 2010;17:709 18. 98.


Recommendations for reducing radiation exposure in myocardial perfusion imaging. J Nucl Cardiol. 2010;17:709 18. 98. Gerber TC, Carr JJ, Arai AE, et al. Ionizing radiation in cardiac imaging: a science advisory from the American Heart Association Committee on Cardiac Imaging of the Council on Clinical Cardiology and Committee on Cardiovascular Imaging and Intervention of the Council on Cardiovascular Radiology and Intervention. Circulation. 2009;119:1056 65. 99. Sharir T, Slomka PJ, Hayes SW, et al. Multicenter trial of high-speed versus conventional single-photon emission computed tomography imaging: quantitative results of myocardial perfusion and left ventric- ular function. J Am Coll Cardiol. 2010;55:1965 74. 100. Berman DS, Kang X, Tamarappoo B, et al. Stress thallium-201/rest technetium-99m sequential dual isotope high-speed myocardial per- fusion imaging. J Am Coll Cardiol Cardiovasc Imaging. 2009;2: 273 82. 101. Bonow RO. High-speed myocardial perfusion imaging: dawn of a new era in nuclear cardiology? J Am Coll Cardiol Cardiovasc Imaging. 2008;1:164 6. 102. Einstein AJ, Henzlova MJ, Rajagopalan S. Estimating risk of cancer associated with radiation exposure from 64-slice computed tomography coronary angiography. JAMA. 2007;298:317 23. 103. Paridon SM, Alpert BS, Boas SR, et al. Clinical stress testing in the pediatric age group: a statement from the American Heart Association Council on Cardiovascular Disease in the Young, Committee on Ath- erosclerosis, Hypertension, and Obesity in Youth. Circulation. 2006; 113:1905 20. 104. Myers J, Arena R, Franklin B, et al. Recommendations for clinical exercise laboratories: a scientific statement from the american heart association. Circulation. 2009;119:3144 61. 105. Fletcher GF, Balady GJ, Amsterdam EA, et al. Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association. Circulation. 2001;104:1694 740. 106. Christian TF, Miller TD, Bailey KR, et al. Exercise tomographic thallium-201 imaging in patients with severe coronary artery disease and normal electrocardiograms. Ann Intern Med.


Exercise tomographic thallium-201 imaging in patients with severe coronary artery disease and normal electrocardiograms. Ann Intern Med. 1994;121:825 32. 107. Gibbons RJ, Zinsmeister AR, Miller TD, et al. Supine exercise elec- trocardiography compared with exercise radionuclide angiography in noninvasive identification of severe coronary artery disease. Ann Intern Med. 1990;112:743 9. 108. Hachamovitch R, Hayes SW, Friedman JD, et al. Stress myocardial perfusion single-photon emission computed tomography is clinically effective and cost effective in risk stratification of patients with a high likelihood of coronary artery disease (CAD) but no known CAD. J Am Coll Cardiol. 2004;43:200 8. 109. Ladenheim ML, Kotler TS, Pollock BH, et al. Incremental prognostic power of clinical history, exercise electrocardiography and myocardial perfusion scintigraphy in suspected coronary artery disease. Am J Cardiol. 1987;59:270 7. 110. Mattera JA, Arain SA, Sinusas AJ, et al. Exercise testing with myo- cardial perfusion imaging in patients with normal baseline electrocar- diograms: cost savings with a stepwise diagnostic strategy. J Nucl Cardiol. 1998;5:498 506. 111. Metz LD, Beattie M, Hom R, et al. The prognostic value of normal exercise myocardial perfusion imaging and exercise echocardiography: a meta-analysis. J Am Coll Cardiol. 2007;49:227 37. 112. Mowatt G, Vale L, Brazzelli M, et al. Systematic review of the effectiveness and cost-effectiveness, and economic evaluation, of myo- cardial perfusion scintigraphy for the diagnosis and management of angina and myocardial infarction. Health Technol Assess. 2004;8: iii 207. 113. Nallamothu N, Ghods M, Heo J, et al. Comparison of thallium-201 single-photon emission computed tomography and electrocardio- graphic response during exercise in patients with normal rest electro- cardiographic results. J Am Coll Cardiol. 1995;25:830 6. Fihn et al Stable Ischemic Heart Disease: Full Text e437 114. Sabharwal NK, Stoykova B, Taneja AK, et al.


Fihn et al Stable Ischemic Heart Disease: Full Text e437 114. Sabharwal NK, Stoykova B, Taneja AK, et al. A randomized trial of exercise treadmill ECG versus stress SPECT myocardial perfusion imaging as an initial diagnostic strategy in stable patients with chest pain and suspected CAD: cost analysis. J Nucl Cardiol. 2007;14: 174 86. 115. Shaw LJ, Iskandrian AE. Prognostic value of gated myocardial per- fusion SPECT. J Nucl Cardiol. 2004;11:171 85. 116. Simari RD, Miller TD, Zinsmeister AR, et al. Capabilities of supine exercise electrocardiography versus exercise radionuclide angiography in predicting coronary events. Am J Cardiol. 1991;67:573 7. 117. Hachamovitch R, Berman DS, Kiat H, et al. Value of stress myocardial perfusion single photon emission computed tomography in patients with normal resting electrocardiograms: an evaluation of incremental prognostic value and cost-effectiveness. Circulation. 2002;105:823 9. 118. Gulati M, Black HR, Shaw LJ, et al. The prognostic value of a nomogram for exercise capacity in women. N Engl J Med. 2005;353: 468 75. 119. Myers J, Prakash M, Froelicher V, et al. Exercise capacity and mor- tality among men referred for exercise testing. N Engl J Med. 2002; 346:793 801. 120. Tanaka H, Monahan KD, Seals DR. Age-predicted maximal heart rate revisited. J Am Coll Cardiol. 2001;37:153 6. 121. Pinkstaff S, Peberdy MA, Kontos MC, et al. Quantifying exertion level during exercise stress testing using percentage of age-predicted maximal heart rate, rate pressure product, and perceived exertion. Mayo Clin Proc. 2010;85:1095 100. 122. Gulati M, Shaw LJ, Thisted RA, et al. Heart rate response to exercise stress testing in asymptomatic women: the St. James women take heart project. Circulation. 2010;122:130 7. 123. Carnethon MR, Gulati M, Greenland P. Prevalence and cardiovascular disease correlates of low cardiorespiratory fitness in adolescents and adults. JAMA. 2005;294:2981 8. 124.


Carnethon MR, Gulati M, Greenland P. Prevalence and cardiovascular disease correlates of low cardiorespiratory fitness in adolescents and adults. JAMA. 2005;294:2981 8. 124. Gupta S, Rohatgi A, Ayers CR, et al. Cardiorespiratory fitness and classification of risk of cardiovascular disease mortality. Circulation. 2011;123:1377 83. 125. Lauer MS. How will exercise capacity gain enough respect? Circu- lation. 2011;123:1364 6. 126. Mark DB, Hlatky MA, Harrell FE Jr, et al. Exercise treadmill score for predicting prognosis in coronary artery disease. Ann Intern Med. 1987; 106:793 800. 127. Mark DB, Shaw L, Harrell FE Jr, et al. Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease. N Engl J Med. 1991;325:849 53. 128. Cheezum MK, Hulten EA, Taylor AJ, et al. Cardiac CT angiography compared with myocardial perfusion stress testing on downstream resource utilization. J Cardiovasc Comput Tomogr. 2011;5:101 9. 129. Min JK, Shaw LJ, Berman DS, et al. Costs and clinical outcomes in individuals without known coronary artery disease undergoing coronary computed tomographic angiography from an analysis of Medicare category III transaction codes. Am J Cardiol. 2008;102: 672 8. 130. Min JK, Kang N, Shaw LJ, et al. Costs and clinical outcomes after coronary multidetector CT angiography in patients without known coronary artery disease: comparison to myocardial perfusion SPECT. Radiology. 2008;249:62 70. 131. Fazel R, Shaw LJ. Radiation exposure from radionuclide myocardial perfusion imaging: concerns and solutions. J Nucl Cardiol. 2011;18: 562 5. 132. Garber AM, Solomon NA. Cost-effectiveness of alternative test strategies for the diagnosis of coronary artery disease. Ann Intern Med. 1999;130:719 28. 133. Kuntz KM, Fleischmann KE, Hunink MG, et al. Cost-effectiveness of diagnostic strategies for patients with chest pain. Ann Intern Med. 1999;130:709 18. 134. Lorenzoni R, Cortigiani L, Magnani M, et al.


1999;130:709 18. 134. Lorenzoni R, Cortigiani L, Magnani M, et al. Cost-effectiveness anal- ysis of noninvasive strategies to evaluate patients with chest pain. J Am Soc Echocardiogr. 2003;16:1287 91. 135. Marwick TH, Shaw L, Case C, et al. Clinical and economic impact of exercise electrocardiography and exercise echocardiography in clinical practice. Eur Heart J. 2003;24:1153 63. 136. Otero HJ, Rybicki FJ, Greenberg D, et al. Cost-effective diagnostic cardiovascular imaging: when does it provide good value for the money? Int J Cardiovasc Imaging. 2010;26:605 12. 137. Shaw LJ, Marwick TH, Berman DS, et al. Incremental costeffec- tiveness of exercise echocardiography vs. SPECT imaging for the evaluation of stable chest pain. Eur Heart J. 2006;27:2448 58. 138. Trikalinos TA, Siebert U, Lau J. Decision-analytic modeling to evaluate benefits and harms of medical tests: uses and limitations. Med Decis Making. 2009;29:e22 e29. 139. Halpern EJ, Fischman D, Savage MP, et al. Decision analytic model for evaluation of suspected coronary disease with stress testing and coronary CT angiography. Acad Radiol. 2010;17:577 86. 140. Min JK, Gilmore A, Budoff MJ, et al. Cost-effectiveness of coronary CT angiography versus myocardial perfusion SPECT for evaluation of patients with chest pain and no known coronary artery disease. Radiology. 2010;254:801 8. 141. Hachamovitch R, Nutter B, Hlatky M, et al. Patient Management After Noninvasive Cardiac Imaging Results From SPARC (Study of Myo- cardial Perfusion and Coronary Anatomy Imaging Roles in Coronary Artery Disease). J Am Coll Cardiol. 2012;59:462 74. 142. Shreibati JB, Baker LC, Hlatky MA. Association of coronary CT angiography or stress testing with subsequent utilization and spending among Medicare beneficiaries. JAMA. 2011;306:2128 36. 143. Ladapo JA, Jaffer FA, Hoffmann U, et al. Clinical outcomes and cost-effectiveness of coronary computed tomography angiography in the evaluation of patients with chest pain. J Am Coll Cardiol. 2009; 54:2409 22. 144.


Clinical outcomes and cost-effectiveness of coronary computed tomography angiography in the evaluation of patients with chest pain. J Am Coll Cardiol. 2009; 54:2409 22. 144. Bruder O, Schneider S, Nothnagel D, et al. EuroCMR (European Cardiovascular Magnetic Resonance) registry: results of the German pilot phase. J Am Coll Cardiol. 2009;54:1457 66. 145. Gianrossi R, Detrano R, Mulvihill D, et al. Exercise-induced ST depression in the diagnosis of coronary artery disease. A metaanalysis. Circulation. 1989;80:87 98. 146. Kwok Y, Kim C, Grady D, et al. Meta-analysis of exercise testing to detect coronary artery disease in women. Am J Cardiol. 1999;83: 660 6. 147. Shaw LJ, Mieres JH, Hendel RH, et al. Comparative Effectiveness of exercise electrocardiography with or without myocardial perfusion single photon emission computed tomography in women with sus- pected coronary artery disease: results from the What Is the Optimal Method for Ischemia Evaluation in Women (WOMEN) trial. Circu- lation. 2011;124:1239 49. 148. Biagini E, Shaw LJ, Poldermans D, et al. Accuracy of non-invasive techniques for diagnosis of coronary artery disease and prediction of cardiac events in patients with left bundle branch block: a metaanalysis. Eur J Nucl Med Mol Imaging. 2006;33:1442 51. 149. Geleijnse ML, Krenning BJ, Soliman OI, et al. Dobutamine stress echocardiography for the detection of coronary artery disease in women. Am J Cardiol. 2007;99:714 7. 150. Imran MB, Palinkas A, Picano E. Head-to-head comparison of dipyr- idamole echocardiography and stress perfusion scintigraphy for the detection of coronary artery disease: a meta-analysis. Comparison between stress echo and scintigraphy. Int J Cardiovasc Imaging. 2003; 19:23 8. 151. Mahajan N, Polavaram L, Vankayala H, et al. Diagnostic accuracy of myocardial perfusion imaging and stress echocardiography for the diagnosis of left main and triple vessel coronary artery disease: a comparative meta-analysis. Heart. 2010;96:956 66. 152.


Diagnostic accuracy of myocardial perfusion imaging and stress echocardiography for the diagnosis of left main and triple vessel coronary artery disease: a comparative meta-analysis. Heart. 2010;96:956 66. 152. Marcassa C, Bax JJ, Bengel F, et al. Clinical value, costeffectiveness, and safety of myocardial perfusion scintigraphy: a position statement. Eur Heart J. 2008;29:557 63. 153. Nandalur KR, Dwamena BA, Choudhri AF, et al. Diagnostic per- formance of stress cardiac magnetic resonance imaging in the detection of coronary artery disease: a meta-analysis. J Am Coll Cardiol. 2007; 50:1343 53. 154. Picano E, Molinaro S, Pasanisi E. The diagnostic accuracy of pharma- cological stress echocardiography for the assessment of coronary artery disease: a meta-analysis. Cardiovasc Ultrasound. 2008;60:30. Pub- lished online 2008 June 19, doi:10.1186/1476-7120-6-30. 155. Underwood SR, Shaw LJ, Anagnostopoulos C, et al. Myocardial per- fusion scintigraphy and cost effectiveness of diagnosis and man- agement of coronary heart disease. Heart. 2004;90 Suppl 5:v34 v36. 156. Underwood SR, Anagnostopoulos C, Cerqueira M, et al. Myocardial perfusion scintigraphy: the evidence. Eur J Nucl Med Mol Imaging. 2004;31:261 91. 157. Hamon M, Fau G, Nee G, et al. Meta-analysis of the diagnostic performance of stress perfusion cardiovascular magnetic resonance for detection of coronary artery disease. J Cardiovasc Magn Reson. 2010; 12:29. 158. Schuetz GM, Zacharopoulou NM, Schlattmann P, et al. Metaanalysis: noninvasive coronary angiography using computed tomography versus magnetic resonance imaging. Ann Intern Med. 2010;152:167 77. 159. Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008;52:1724 32. 160. Hamon M, Biondi-Zoccai GG, Malagutti P, et al.


2008;52:1724 32. 160. Hamon M, Biondi-Zoccai GG, Malagutti P, et al. Diagnostic per- formance of multislice spiral computed tomography of coronary arteries as compared with conventional invasive coronary angiography: a meta-analysis. J Am Coll Cardiol. 2006;48:1896 910. 161. Janne d Othee B, Siebert U, Cury R, et al. A systematic review on diagnostic accuracy of CT-based detection of significant coronary artery disease. Eur J Radiol. 2008;65:449 61. 162. Meijboom WB, Meijs MF, Schuijf JD, et al. Diagnostic accuracy of 64-slice computed tomography coronary angiography: a prospective, multicenter, multivendor study. J Am Coll Cardiol. 2008;52:2135 44. 163. Miller JM, Rochitte CE, Dewey M, et al. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med. 2008;359:232 36. 164. Schuijf JD, Bax JJ, Shaw LJ, et al. Meta-analysis of comparative diagnostic performance of magnetic resonance imaging and multislice computed tomography for noninvasive coronary angiography. Am Heart J. 2006;151:404 11. 165. Stein PD, Beemath A, Kayali F, et al. Multidetector computed tomography for the diagnosis of coronary artery disease: a systematic review. Am J Med. 2006;119:203 16. 166. Sun Z, Jiang W. Diagnostic value of multislice computed tomography angiography in coronary artery disease: a meta-analysis. Eur J Radiol. 2006;60:279 86. 167. Underwood SR, Godman B, Salyani S, et al. Economics of myocardial perfusion imaging in Europe the EMPIRE Study. Eur Heart J. 1999; 20:157 66. 168. Nucifora G, Schuijf JD, van Werkhoven JM, et al. Relationship between obstructive coronary artery disease and abnormal stress testing in patients with paroxysmal or persistent atrial fibrillation. Int J Car- diovasc Imaging. 2011;27:777 85. 169. Greenwood JP, Maredia N, Younger JF, et al. Cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary heart disease (CE-MARC): a prospective trial. Lancet. 2012;379:453 60. 170. Hundley WG, Hamilton CA, Thomas MS, et al.


2012;379:453 60. 170. Hundley WG, Hamilton CA, Thomas MS, et al. Utility of fast cine magnetic resonance imaging and display for the detection of myo- cardial ischemia in patients not well suited for second harmonic stress echocardiography. Circulation. 1999;100:1697 702. 171. Nagel E, Lehmkuhl HB, Bocksch W, et al. Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocar- diography. Circulation. 1999;99:763 70. 172. Schwitter J, Wacker CM, van Rossum AC, et al. MR-IMPACT: com- parison of perfusion-cardiac magnetic resonance with singlephoton emission computed tomography for the detection of coronary artery disease in a multicentre, multivendor, randomized trial. Eur Heart J. 2008;29:480 9. 173. de Azevedo CF, Hadlich MS, Bezerra SG, et al. Prognostic value of CT angiography in patients with inconclusive functional stress tests. J Am Coll Cardiol Cardiovasc Imaging. 2011;4:740 51. 174. Sarwar A, Shaw LJ, Shapiro MD, et al. Diagnostic and prognostic value of absence of coronary artery calcification. J Am Coll Cardiol Cardiovasc Imaging. 2009;2:675 88. 175. Mieres JH, Shaw LJ, Arai A, et al. Role of noninvasive testing in the clinical evaluation of women with suspected coronary artery disease: Consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association. Circulation. 2005;111:682 96. 176. Nieman K, Galema TW, Neefjes LA, et al. Comparison of the value of coronary calcium detection to computed tomographic angiography and exercise testing in patients with chest pain. Am J Cardiol. 2009;104: 1499 504. 177. Alexander KP, Shaw LJ, Shaw LK, et al. Value of exercise treadmill testing in women. J Am Coll Cardiol. 1998;32:1657 64. 178. Daugherty SL, Magid DJ, Kikla JR, et al.


1998;32:1657 64. 178. Daugherty SL, Magid DJ, Kikla JR, et al. Gender differences in the prognostic value of exercise treadmill test characteristics. Am Heart J. 2011;161:908 14. 179. Ovrehus KA, Jensen JK, Mickley HF, et al. Comparison of usefulness of exercise testing versus coronary computed tomographic angiography for evaluation of patients suspected of having coronary artery disease. Am J Cardiol. 2010;105:773 9. 180. Shaw LJ, Peterson ED, Shaw LK, et al. Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups. Circu- lation. 1998;98:1622 30. 181. Mulvagh SL, DeMaria AN, Feinstein SB, et al. Contrast echocardiog- raphy: current and future applications. J Am Soc Echocardiogr. 2000; 13:331 42. 182. Abdelmoneim SS, Bernier M, Dhoble A, et al. Assessment of myo- cardial perfusion during adenosine stress using real time threedimen- sional and two-dimensional myocardial contrast echocardiography: comparison with single-photon emission computed tomography. Echo- cardiography. 2010;27:421 9. 183. Berman D, Hachamovitch R, Shaw L, et al. Nuclear Cardiology. In: Fuster V, Alexander RW, O Rourke RA, et al., eds. Hurst s The Heart, 11th ed. New York: The McGraw-Hill Companies, Inc.; 2004: 563 98; 2004. 184. Fukushima K, Javadi MS, Higuchi T, et al. Prediction of short-term cardiovascular events using quantification of global myocardial flow reserve in patients referred for clinical 82Rb PET perfusion imaging. J Nucl Med. 2011;52:726 32. 185. El Fakhri G, Kardan A, Sitek A, et al. Reproducibility and accuracy of quantitative myocardial blood flow assessment with (82)Rb PET: com- parison with (13)N-ammonia PET. J Nucl Med. 2009;50:1062 71. 186. Yoshinaga K, Katoh C, Manabe O, et al. Incremental Diagnostic Value of Regional Myocardial Blood Flow Quantification Over Relative Perfusion Imaging With Generator-Produced Rubidium-82 PET. Circ J. 2011;75:2628 34. 187. Duvall WL, Sweeny J, Croft LB, et al.


2011;75:2628 34. 187. Duvall WL, Sweeny J, Croft LB, et al. SPECT myocardial perfusion imaging in morbidly obese patients: image quality, hemodynamic response to pharmacologic stress, and diagnostic and prognostic value. J Nucl Cardiol. 2006;13:202 9. 188. Berman DS, Kang X, Nishina H, et al. Diagnostic accuracy of gated Tc-99m sestamibi stress myocardial perfusion SPECT with combined supine and prone acquisitions to detect coronary artery disease in obese and nonobese patients. J Nucl Cardiol. 2006;13:191 201. 189. Slomka PJ, Nishina H, Abidov A, et al. Combined quantitative supine-prone myocardial perfusion SPECT improves detection of coronary artery disease and normalcy rates in women. J Nucl Cardiol. 2007;14:44 52. 190. Pazhenkottil AP, Ghadri J-R, Nkoulou RN, et al. Improved outcome prediction by SPECT myocardial perfusion imaging after CT atten- uation correction. J Nucl Med. 2011;52:196 200. 191. Sampson UK, Dorbala S, Limaye A, et al. Diagnostic accuracy of rubidium-82 myocardial perfusion imaging with hybrid positron emission tomography/computed tomography in the detection of coronary artery disease. J Am Coll Cardiol. 2007;49:1052 8. 192. Nandalur KR, Dwamena BA, Choudhri AF, et al. Diagnostic per- formance of positron emission tomography in the detection of coronary artery disease: a meta-analysis. Acad Radiol. 2008;15:444 51. 193. Bateman TM, Heller GV, McGhie AI, et al. Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET: comparison with ECG-gated Tc-99m sestamibi SPECT. J Nucl Cardiol. 2006;13: 24 33. 194. Pilz G, Eierle S, Heer T, et al. Negative predictive value of normal adenosine-stress cardiac MRI in the assessment of coronary artery disease and correlation with semiquantitative perfusion analysis. J Magn Reson Imaging. 2010;32:615 21. 195. Koo B-K, Erglis A, Doh J-H, et al. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms.


Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia- Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study. J Am Coll Cardiol. 2011;58:1989 97. 196. George RT, Arbab-Zadeh A, Cerci RJ, et al. Diagnostic performance of combined noninvasive coronary angiography and myocardial perfusion imaging using 320-MDCT: the CT angiography and perfusion methods Fihn et al Stable Ischemic Heart Disease: Full Text e439 of the CORE320 multicenter multinational diagnostic study. AJR Am J Roentgenol. 2011;197:829 37. 197. Valdiviezo C, Ambrose M, Mehra V, et al. Quantitative and qualitative analysis and interpretation of CT perfusion imaging. J Nucl Cardiol. 2010;17:1091 100. 198. Feuchtner G, Goetti R, Plass A, et al. Adenosine stress high-pitch 128-slice dual-source myocardial computed tomography perfusion for imaging of reversible myocardial ischemia: comparison with magnetic resonance imaging. Circ Cardiovasc Imaging. 2011;4:540 9. 199. Cury RC, Magalhaes TA, Borges AC, et al. Dipyridamole stress and rest myocardial perfusion by 64-detector row computed tomography in patients with suspected coronary artery disease. Am J Cardiol. 2010; 106:310 5. 200. Rocha-Filho JA, Blankstein R, Shturman LD, et al. Incremental value of adenosine-induced stress myocardial perfusion imaging with dual- source CT at cardiac CT angiography. Radiology. 2010;254:410 9. 201. Blankstein R, Shturman LD, Rogers IS, et al. Adenosine-induced stress myocardial perfusion imaging using dual-source cardiac computed tomography. J Am Coll Cardiol. 2009;54:1072 84. 202. van Werkhoven JM, Schuijf JD, Gaemperli O, et al. Prognostic value of multislice computed tomography and gated single-photon emission computed tomography in patients with suspected coronary artery disease. J Am Coll Cardiol. 2009;53:623 32. 203. Hachamovitch R, Di Carli MF. Nuclear cardiology will remain the gatekeeper over CT angiography. J Nucl Cardiol. 2007;14:634 44. 204. Di Carli MF, Dorbala S, Curillova Z, et al.