Chapter 17: Evaluation of Patients with Known Coronary Artery Disease

In the last 40 years, there has been a dramatic decline in cardiovascular mortality. Over the past decade alone, the rate of death attributable to cardiovascular disease has decreased by 30%.¹ This trend is credited primarily to the development and implementation of effective treatment strategies including medical therapy, interventions such as coronary artery bypass graft surgery (CABG) and percutaneous coronary interventions (PCIs), and successful treatment for acute myocardial infarction (MI). The decision to undergo myocardial perfusion imaging (MPI) evaluation following the diagnosis of ischemic heart disease is an important one, particularly in asymptomatic patients. This chapter will evaluate the role of stress MPI in patients with known CAD in a variety of settings, including medical therapy, postinterventions, and following MI.

Indications for Stress Myocardial Perfusion Imaging

Stress testing is an important tool in the longitudinal assessment of patients with known coronary disease, especially when there is a change in the frequency or pattern of symptoms. However, several factors may preclude the use of exercise tolerance testing (ETT) without imaging to make management decisions, as discussed in Chapters 8 and 26. The American College of Cardiology/American Heart Association (ACC/AHA) guidelines for ETT strongly recommend an imaging study as part of the evaluation in patients unable to exercise and in those with baseline EGG abnormalities (pre-excitation, paced ventricular rhythm, ≥1 mm resting ST-segment depression, and complete left bundle branch block [LBBB]).² The use of digoxin, presence of left ventricular hypertrophy (LVH), or any resting ST-segment depression decreases the specificity of exercise testing while sensitivity may remain unaffected.² Importantly, several other subsets of patients benefit incrementally with the use of radionuclide imaging, including patients with previous MI and/or coronary revascularization procedures (CABG or PCI), patients with prior angiography demonstrating significant disease (where identification of the lesion causing myocardial ischemia is important), individuals with high risk for future events (e.g., diabetics), and patients with a previous positive MPI.^2–6

Timing of Imaging of Follow-Up in Patients with Stable Coronary Artery Disease

Many patients with CAD undergo stress MPI for postinterventional assessment. Stress MPI is indicated as part of initial risk assessment and/or prior to planning PCI or CABG. It is also performed during follow-up after revascularization (PCI or CABG) or modification of medical therapy.

The role of stress MPI in stable CAD is linked to an effort to identify individuals at higher or lower risk for future cardiac events. Unless cardiac catheterization is indicated, patients with known CAD who present with changing symptoms suggestive of ischemia should likely first undergo stress imaging, to assess the risk of future events.² Furthermore, localization of ischemia, identification of extent and severity of ischemic burden, and assessment of left ventricular performance are desirable for most patients who are being evaluated for intervention or titration of medical therapy.⁷ Despite some limitations in the setting of multivessel disease,⁸ MPI remains the test of choice for identifying the culprit lesion causing ischemic symptoms. Routine testing in patients with stable symptoms and in patients with severe comorbidities that limit life expectancy or preclude revascularization is not supported by the literature.²

Although studies in nuclear cardiology have provided substantial data regarding prognosis and risk stratification, there is limited evidence regarding the widespread practice of follow-up or serial MPI testing. Clinicians must use their best judgment to answer important questions: What constitutes a "definite" change that is outside the limit of reproducibility of the test? What constitutes a "clinically significant" improvement or worsening? What degree of improvement should be expected after medical management or intervention? If the patient does improve symptomatically on medical therapy, does this portray a favorable prognosis? Nonetheless, a worsening in myocardial ischemic burden by ≥5% seems to correlate with adverse outcome. Farzaneh-Far et al. followed 1425 patients with angiographically documented CAD who underwent at least two SPECT MPI scans; patients were divided into three groups based on intervention received, medical therapy, and revascularization therapy. After a mean follow-up of 5.8 years, ischemic worsening by ≥5% was a significant and independent predictor of death or MI. Importantly, worsening ischemia of ≥5% provided improvement in risk classification compared to known risk predictors.⁹

To address some of the issues related to management strategy in patients with stable ischemic heart disease, the COURAGE trial compared outcomes of patients treated with PCI plus optimal medical therapy (OMT) versus OMT alone.¹⁰ The trial confirmed that, in low-risk patients, the hard endpoints of death and MI were relatively infrequent and were not reduced by PCI when compared with OMT alone.¹¹ The nuclear substudy of the COURAGE trial compared outcomes of patients with baseline stress MPI and a repeat stress MPI after 6 to 18 months of treatment.¹² These analyses demonstrated that PCI added to OMT was more effective in reducing ischemia and improving angina than OMT alone, particularly in patients with moderate-to-severe pretreatment ischemia. Improvement in the ischemic burden on stress MPI occurred in 33% of patients in the PCI plus OMT arm, compared with 19% of patients in the OMT-alone group. Patients with moderate-to-severe pretreatment ischemia had a 78% improvement in ischemia, compared with 52% in those who had mild pretreatment ischemia (p = 0.007). Furthermore, ischemia reduction was associated with a lower risk of death/MI, whereas residual ischemia was associated with a higher risk of death/MI regardless of the treatment strategy (Fig. 17-1). There was a graded relationship between event risk and residual ischemic burden: none (0%) of the patients with no ischemia had death or MI events, while 39.3% of the patients with ≥10% ischemic myocardium had events during follow-up. These data suggest that patients with known CAD and moderate-to-severe perfusion abnormalities would benefit from both OMT and, when appropriate, coronary revascularization. Thus, MPI may be useful in determining the need for coronary revascularization so as to hopefully improve outcomes.

The timing of MPI after revascularization has traditionally been dependent on the presence or absence of symptoms suggestive of myocardial ischemia. The role of MPI for risk stratification in patients who have stable symptoms or those who are asymptomatic is controversial. Shah et al.¹³ evaluated the patterns of stress MPI utilization after revascularization in community practices, and determined that out of 28,177 patients who underwent revascularization (21,046 PCI and 7131 CABG); 59% had at least 1 cardiac stress test within 24 months. As shown in Figure 17-2, the incidence of testing spiked at 6 and 12 months after revascularization, suggesting an association with elective follow-up visits or revascularization anniversary; 11% of those tested underwent subsequent cardiac catheterization and only 5% had repeat revascularization. These findings highlight the low yield of routine testing after revascularization and are aligned with the latest iteration of the ACCF/AHA/American Society of Nuclear Cardiology (ASNC) multimodality AUC for risk assessment of stable ischemic heart disease in which repeat stress imaging studies were deemed "appropriate" for patients with new/worsening symptoms or incomplete revascularization but "rarely appropriate" in asymptomatic patients <2 years post-PCI and "may be appropriate" ≥2 years after PCI (Table 17-1).^14–17 These data suggest that too many stress MPI studies have been performed too soon following revascularization, thus highlighting the importance of adhering to evidence-based practice guidelines and AUC. The value of stress MPI in risk assessment is greatest in symptomatic patients to identify those who would benefit from coronary revascularization.¹⁵

Coronary Artery Bypass Graft Surgery

CABG is the most commonly performed cardiac surgery.^18,19 The long-term effectiveness of this procedure is limited by graft occlusion and progression of native disease. Evaluation of post-CABG patients with stress MPI depends on the presence or absence of symptoms as well as timing from the surgical procedure.²⁰

In a study of 294 patients ≥5 years post-CABG, Palmas et al. demonstrated that Tl-201 reversibility score (a global measure of ischemic burden) and increased lung uptake added significant prognostic information to a clinical model.⁶ Similarly, in a study of 1765 post-CABG patients (mean 7.1 ± 5.0 years) who underwent SPECT MPI, Zellweger et al. demonstrated that patients >5 years post-CABG, irrespective of symptoms, and symptomatic patients ≤5 years post-CABG, benefited from MPI testing, as the assessment of ischemia provided a guide to appropriate therapy.²¹ However, asymptomatic patients ≤5 years post-CABG have a low cardiac death rate (1.3%) and did not benefit from MPI. Mortality rates were significantly higher in patients with moderate (2.1%) and severely (3.1%) abnormal summed stress score (Fig. 17-3). In addition, in a cohort of 362 patients who underwent SPECT MPI after CABG, Acampa et al. found that event-free survival was 96% in patients with normal SPECT MPI, 86% in those with abnormal MPI without ischemia, and 70% in those with myocardial ischemia (p = 0.008), suggesting that SPECT MPI may be a useful tool for risk stratification 5 years after CABG.²² However, the question remains as to whether coronary revascularization in asymptomatic patients post-CABG can improve patients' outcomes.

Based on these data, the most recent 2013 multimodality AUC for stable ischemic heart disease considered MPI to be "appropriate" for the evaluation of symptomatic patients any time after revascularization as well as asymptomatic patients with incomplete revascularization (Table 17-1).¹⁴ On the other hand, MPI use was considered "may be appropriate" for the evaluation of asymptomatic patients ≥5 years post-CABG, but "rarely appropriate" for asymptomatic patients <5 years post-CABG (Table 17-1). Current multimodality appropriate use criteria (AUC) for radionuclide imaging therefore argue against routine testing of asymptomatic patients, but in selected cases testing may be appropriate in asymptomatic patients >5 years post-CABG.^14,22,23

Percutaneous Coronary Intervention

The explosion of PCI use in increasingly complex lesions and higher-risk patients with single- or multivessel disease has created a necessity for detection of restenosis and disease progression as well as risk assessment. A number of clinical studies have documented the usefulness of stress SPECT MPI for identifying restenosis in patients after PCI.^24,25 The optimal time of performing SPECT imaging after PCI is somewhat controversial.¹⁴ Initial studies in the era of balloon angioplasty reported a high frequency of false-positive transient perfusion defects when SPECT imaging was performed in the first few weeks after angioplasty.^26,27 Currently, MPI is considered reasonable in patients with atypical symptoms within a few weeks post-PCI, or those in whom additional ischemia detection is warranted due to incomplete revascularization. Patients with typical symptoms following PCI are best evaluated in the catheterization laboratory. Studies by Giedd et al.²⁸ and Zellweger et al.²⁹ suggested that when performed ≥6 months following PCI, MPI can reliably identify patients most at risk for poor long-term outcome. However, there are no randomized clinical data to support this. Peterson et al. evaluated a cohort of 1848 patients who had PCI, of whom 241 were asymptomatic when they had follow-up SPECT MPI. Among those who had the study within the first 2 years (n = 138), no patient required revascularization, whereas in those who had the study after 2 years (n = 103), two patients underwent revascularization. These results suggest that routine stress testing after PCI in asymptomatic patients has low yield, especially within the first 2 years.³⁰

When performed shortly after PCI, MPI can identify problems related to the target vessel. Zellweger et al. investigated a cohort of 476 patients who underwent SPECT MPI 6 months after PCI and followed for a mean of 1 year. As shown in Figure 17-4, those who had target vessel ischemia had significantly higher rate of major adverse cardiac events, mostly driven by an increase in target vessel revascularization.¹⁷ In this cohort, ischemia was silent in 68% of patients. However, the impact of coronary revascularization on the outcomes of patients with silent target vessel ischemia is not established.

In contrast, when performed late after PCI, SPECT MPI often identifies CAD in remote arteries, rather than in the target vessel. In a cohort of patients who underwent routine SPECT MPI 5 years after PCI, Zellweger et al. demonstrated that abnormal perfusion imaging was frequent irrespective of symptoms, and its utility lies in the detection of persistent or progressive CAD in remote vessel areas rather than in the diagnosis of late intervention-related problems in the treated vessels.²³ These findings are consistent with our understanding of the timeline of in-stent restenosis and PCI-related complications which tend to occur within the first year after intervention.

Thrombolytic Therapy for Acute ST-Segment Elevation Myocardial Infarction (STEMI)

The most effective therapy for patients experiencing STEMI is timely reperfusion therapy with primary PCI. Unfortunately, this is not possible in every setting, and in these cases thrombolytic therapy has been shown to improve myocardial salvage and reduce mortality rate compared to patients not receiving reperfusion therapy. However, even after successful thrombolytic therapy, patients may remain at risk for future events. Post-thrombolysis MPI provides valuable prognostic information by quantifying the infarcted myocardium and the myocardium at risk. Basu et al. demonstrated that reversible perfusion abnormality (ischemia) post-lytic therapy predicts adverse events (death, reinfarction, CHF, and unstable angina) during follow-up (range, 8–32 months) with a hazard ratio of 8.1 (95% CI: 2.7–23.8, p < 0.001).³¹ Similarly, Dakik et al. showed the estimated cardiac event rate after thrombolytic therapy doubled with every 10% decrease in LVEF and 10% increase in MPI defect size.³² Based on these data, select uncomplicated STEMI patients who receive successful thrombolytic therapy are reasonable candidates for stress MPI.

ST-Elevation Myocardial Infarction without Reperfusion Therapy

Patients who survive STEMI without receiving any reperfusion therapy are also at risk for re-infarction, heart failure, and cardiac death. Thus, they are candidates for risk stratification. Clinically unstable post-STEMI patients (heart failure, arrhythmias, hemodynamic instability) and those with clinical or electrocardiographic evidence of recurrent ischemia need to undergo coronary angiography to determine further management. However, those with uncomplicated STEMI may be candidate for noninvasive risk assessment. Pharmacologic stress MPI has been shown to be superior to conventional submaximal ETT with modified Bruce protocol as a risk stratification tool in these patients.^33–37 Stress testing with dipyridamole, adenosine, or regadenoson may be performed safely as early as 2 to 4 days following an uncomplicated MI. This approach can shorten hospital stay, and more importantly, it has been shown to have an excellent prognostic value, as patients with low-risk myocardial perfusion scan (i.e., without evidence of reversible perfusion defect) have low risk for cardiac events.^33–35 Mahmarian et al. showed that a large area of myocardial ischemia (>10% of the left ventricle) on adenosine stress MPI following noncomplicated MI is superior to coronary angiography in separating patients at increased risk for cardiac events from those at low risk.³⁵ These data paved the way for the INSPIRE trial.³⁸ In this multicenter prospective study, Mahmarian et al. enrolled 728 clinically stable survivors of acute MI (ST-elevation and non–ST-elevation ACS) who did not receive coronary revascularization and underwent adenosine SPECT MPI within 10 days of admission. Three risk groups were prospectively defined based on perfusion defect size (PDS) and ischemia perfusion defect size (IPDS); low risk (PDS <20%), intermediate risk (PDS >20% and IPDS <10%), and high risk (PDS >20% and IPDS >10%). The study also prospectively defined discharge and treatment strategies on the basis of MPI risk group and ejection fraction. The cardiac events/death and reinfarction rates were 5.4%, 1.8% in the low-risk, 14%, 9.2% in the intermediate-risk, and 18.6%, 11.6% in the high-risk group (p < 0.0001), demonstrating a significant increase in event rates with increasing burden of perfusion abnormalities. Furthermore, the study established the value of commonly measured MPI variables to improve the precision for assessing risk beyond TIMI risk score and ejection fraction, as shown in Figure 17-5.³⁸ More importantly, the study prospectively demonstrated that low-risk patients are candidates for safe early discharge, whereas patients in the intermediate and high-risk groups should be considered for early invasive management. Moreover, in the high-risk group, coronary revascularization was associated with significant reduction in the cardiac event rate (10% vs. 32%, p = 0.049). Thus, the INSPIRE trial demonstrated that MPI not only defines risk, but can also guide patient management. These findings may also be relevant in patients who present late after an ST-elevation MI.³⁸

Non–ST-Elevation Acute Coronary Syndrome

It is generally accepted that intermediate- and high-risk patients with non–ST-elevation acute coronary syndrome (ACS) benefit from early invasive strategy aimed at early coronary revascularization.³⁹ However, low-risk non–ST-elevation ACS, such as those with low TIMI risk score and negative biomarkers, are candidates for a noninvasive risk assessment, especially if they respond well to initial medical management.^40–42 In addition, noninvasive risk stratification prior to invasive testing should be considered in ACS patients with a relative contraindication for coronary angiography, such as those with bleeding diatheses or chronic kidney disease.⁴³

Exercise or pharmacologic stress MPI can be used safely to assess risk for cardiac events (death or MI) in patients with unstable angina following the initial response to medical management.^44–46 The safety of adenosine and dipyridamole vasodilator stress performed 2 to 7 days after ACS is well established.^33–36 More recently, regadenoson vasodilator stress has been shown to be associated with similarly low adverse event rates among patients undergoing in-hospital MPI for the assessment of ACS or elevated cardiac biomarkers.³⁷

SPECT MPI has been shown to be safe and effective for risk stratification in patients presenting with ACS. Brown et al. and Stratmann et al. demonstrated that stress MPI can effectively risk stratify patients with unstable angina for long-term adverse cardiac events, and thus identifying patients with inducible ischemia as candidates for coronary angiography and revascularization.^44,46 However, with demonstrated effectiveness of early invasive management of ACS, the role of stress MPI in the risk stratification of ACS patients in the modern era has significantly diminished. Nonetheless, there may be a role for MPI in the risk assessment of low-risk non–ST-elevation ACS and those with relative contraindication for coronary angiography.³⁹

Intensive medical therapy with risk factor modification is essential in the management of patients with coronary artery disease. While high-risk patients gain a survival benefit from CABG, low- and moderate-risk patients have equivalent outcomes with respect to mortality with either approach (medical management or revascularization). Appropriate medical therapy would include antiplatelet agents, beta-blockers, lipid-lowering agents, and probably angiotensin-converting enzyme (ACE) inhibitors in diabetics and patients with impaired LV function. Since the degree and extent of ischemia predict future events, MPI has been used to assess the impact of medical management on the burden of myocardial ischemia in patients with known coronary disease. Importantly, the use of antianginal medications is usually avoided before performing diagnostic SPECT MPI studies for the detection of CAD, however, it is important to perform the studies while patient is on antianginal regimen for the purpose of assessing prognosis and response to therapy. Data from Mahmarian et al. demonstrated that quantitative exercise Tl-201 MPI is highly reproducible and can be used to accurately interpret temporal changes in MPI in individual patients.⁴⁷ Moreover, in the ADVANCE MPI trials, Mahmarian et al. demonstrated, in same patient controls, that adenosine and regadenoson produce similar perfusion defects; thus temporal changes with repeat testing can be followed when either of these vasodilator stress agents is used.⁴⁸

The beneficial impact of various pharmacologic interventions on the clinical outcomes of patients with CAD has been well established. Medical therapy has been associated with improvement in myocardial perfusion defects as a result of either decreased oxygen demand (beta blockers)^49–51 or improved coronary blood flow (nitrates, calcium channel blockers [CCBs], and statins).^52–54 In asymptomatic patients with CAD and known myocardial perfusion abnormalities, the 2013 ACCF/AHA/ASNC multimodality AUC for radionuclide MPI deem stress testing "rarely appropriate" when last stress imaging study was done <2 years prior, but "may be appropriate" if previous stress imaging was performed ≥2 years prior.⁴⁰

Beta Blockers

Among the antianginal medications, beta-blockers have been shown in multiple studies to markedly decrease the burden of exercise-induced ischemia or even normalize the test.^49,55 The anti-ischemic effect of beta-blockers is mediated primarily by decreasing the heart rate, prolonging diastole, increasing coronary perfusion time and myocardial oxygen extraction, and decreasing myocardial oxygen consumption in ischemic tissue.⁵⁰ At the cellular level, beta blockers alter myocyte metabolism providing additional myocardial protection against ischemia. One week of oral propranolol treatment has been shown to improve MPI abnormalities in men with established CAD.⁴⁹ Similarly, acute propranolol administration in patients with dobutamine-induced reversible perfusion abnormalities has been shown to dampen heart rate response (peak heart rate 83 ± 18 vs. 125 ± 17, p < 0.001), rate–pressure product (14,169 ± 4,248 vs. 19,894 ± 3,985; p < 0.001), and myocardial ischemia score (6.9 ± 5.8 vs. 10.1 ± 7.1, p = 0.047) despite a higher infusion dose.⁵⁰ The extent of perfusion abnormalities has been shown to be significantly reduced with beta blockers even with the use of vasodilator stress.⁵⁵

Nitrates

The anti-ischemic effect of nitroglycerin has been attributed to the redistribution of blood flow from normal to ischemic myocardium through dilation of collateral vessels. In addition, nitroglycerine reduces myocardial oxygen consumption by producing a systemic venodilation leading to a reduction in systemic venous return, left ventricular dimensions, and myocardial wall stress.

Either in conjunction with beta blockers⁵¹ or alone,^52,54 both of these agents decrease the size of reversible defects (particularly in patients with large ischemic perfusion defects). Mahmarian et al. prospectively evaluated whether short-term (6.1 ± 1.8 days) transdermal nitroglycerin patches could limit the extent of exercise-induced LV ischemia as assessed by quantitative Tl-201 tomography. Patients randomized to receive active patch therapy had a significant reduction in their total perfusion defect size (–8.9 ± 11.1%) compared with placebo-treated patients (−1.8 ± 6.1%, p = 0.04). The reduction in perfusion defect size was most apparent in those with the largest (≥20%) baseline perfusion defects (–11.4 ± 13.4% vs. 1.0 ± 3.6%, respectively, p < 0.02). Nitrate therapy did not significantly reduce heart rate, blood pressure, or double product, in consistence with its known mechanisms of action.⁵⁴

Calcium Channel Blockers

The primary benefit of CCBs seems to be a reduction in myocardial oxygen demand, which is achieved by decreasing arterial tone, peripheral vascular resistance, intraventricular pressure, and wall stress. CCBs also enhance myocardial perfusion through their effects on myocardial microcirculation and metabolism. They improve coronary flow in CAD by selectively dilating larger arterioles and may prevent coronary spasm.⁵²

Limited data suggest that acute administration of nifedipine before exercise planar MPI resulted in significant improvement in perfusion (defined as >20% increase) in approximately one-half of patients and in one-fourth of segments compared with no CCB administration. Chronic administration of nifedipine and nicorandil in two separate studies before exercise SPECT reduced the defect extent and severity.⁵²

Lipid-lowering Agents

The impact of lipid-lowering agents in the secondary prevention of coronary disease has been demonstrated in multiple large studies, such as CARE,⁵³ CTT,⁵⁶ 4S,⁵⁷ TNT,⁵⁸ PROVE-IT,⁵⁹ and JUPITER.⁶⁰ Statins improve endothelial function and preserve coronary perfusion independent of their reduction in cholesterol. They increase smooth muscle relaxation, decrease oxidative stress, and prevent vascular inflammation. Although statins may halt the progression or cause a regression of atherosclerosis as assessed by coronary angiography and intravascular ultrasound, the degree of regression is slight compared with the substantial improvement in clinical outcomes which is likely related to plaque stabilization. Using rest-dipyridamole positron emission tomography (PET), Gould et al. demonstrated that there were statistically significant improvements in size and severity of perfusion abnormalities after intensive 90-day cholesterol lowering compared to baseline control.⁶¹ Thus, short-term intensive cholesterol lowering improves myocardial perfusion before anatomic regression of stenosis occurs. Schwartz et al. used SPECT imaging in patients with CAD and hypercholesterolemia to assess serial changes in myocardial perfusion associated with cholesterol-lowering therapy.⁶² Following improvement in total cholesterol (pretreatment: 223 ± 51, posttreatment: 147 ± 33, p < 0.001), the stress defect score (% ischemic myocardium) was significantly improved (pretreatment: 19 ± 16, posttreatment: 9 ± 13, p = 0.022). Furthermore, the same investigators studied the effect of short-term (6 weeks) or long-term (6 months) pravastatin in dyslipidemic patients with baseline MPI ischemic defects.^63,64 Despite a significant reduction of low-density lipoprotein (LDL) at 6 weeks (33%, p < 0.001), myocardial perfusion scores were reduced only at 6 months (12.6 ± 5.7 at baseline, 9.4 ± 6.2 at 6 months, p < 0.01). The time course of reduced perfusion abnormalities, rather than LDL reduction, paralleled documented clinical benefit.^53,57,61,65

Angiotensin-Converting Enzyme Inhibitors

There is notable evidence that ACE inhibitors exert a beneficial effect in patients with known coronary disease. The mechanism for ACE inhibitors benefit is complex (improved endothelial function, vasodilation and reduced afterload, antiplatelet effect, and inhibition of neurohormonal activation). There is no large study to examine their direct anti-ischemic mechanism using MPI. In two studies, ACE inhibition was associated with improved epicardial⁶⁶ and microvascular blood flow⁶⁷; the mechanism is predominantly endothelium mediated. After 12 weeks of treatment, enalapril delayed the onset of ischemic ST-segment depression during ETT (5.6 ± 1.9 minutes in the enalapril group vs. 4.4 ± 1.3 minutes in the placebo group, p < 0.05) without affecting the double product.⁶⁸ Further studies are needed to elucidate a direct anti-ischemic mechanism of ACE inhibitors and explore the role of MPI in monitoring such an effect.

Lifestyle Modifications

The widespread interest in the noninvasive management of coronary atherosclerosis has brought new attention to the impact of various lifestyle changes on the prognosis of coronary disease. Diet, exercise, and behavioral interventions are generally advised for patients with documented coronary disease. The impact of these changes on the extent of atherosclerosis, as determined by angiography, is modest. However, after 5 years of intensive risk factor modification, the size and severity of perfusion abnormalities on rest-dipyridamole PET imaging improved in the intervention group compared to controls.⁶⁹

The value of stress MPI is well established in patients with CAD for both risk stratification and clinical decision making. This has grown to include risk assessment after coronary revascularization procedures and medical therapies and in patients with ACS. The decision regarding when to repeat testing is difficult and somewhat controversial. Appropriate indications for imaging include any patients who develop new or worsening symptoms or in those with incomplete revascularization when additional revascularization is feasible. Repeat stress MPI "may be appropriate" in asymptomatic patients ≥5 years after CABG or ≥2 years after PCI; imaging before these periods in asymptomatic patients is considered "rarely appropriate."