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.