Assessing prognosis by means of radionuclide perfusion imaging: what technique and which variables should be used?

The prognostic value of exercise and pharmacologic stress myocardial perfusion imaging has been established in thousands of patients evaluated in multiple clinical studies (1–5). The major prognostic variables on stress perfusion images predictive of future cardiac events are a large defect size (.25% of the left ventricle), defects in more than one coronary vascular supply region suggestive of multivessel coronary artery disease (CAD), defect reversibility reflective of inducible ischemia in multiple myocardial scan segments, a large number of nonreversible defects, transient or persistent left ventricular (LV) cavity dilation from stress to rest images, increased lung thallium-201 (Tl-201) uptake and a rest LV ejection fraction measured on gated single-photon emission computed tomography (SPECT) ,40% (6–16). Data from a multicenter registry (17) comprising 8,408 symptomatic patients showed that the number of coronary vascular territories with ischemia (chi-square 40.1, p , 0.0001) and the number of territories with infarction (chi-square 55, p , 0.0001) were independent predictors of cardiac death at a mean follow-up of 2.6 years, even after adjusting for pretest risk. In that analysis, patients with three ischemic territories had a 5.2% mortality rate compared with 2.3% in patients with one ischemic vascular territory identified. Perhaps the most predictive nonimaging variable for future cardiac events is failure to attain a workload . 6 metabolic equivalents (METS) (18). Other high exercise electrocardiographic (ECG) stress test variables are failure to attain $85% of maximal predicted heart rate for age, . 2.0-mm horizontal or downsloping ST segment depression in multiple ECG leads and an inadequate blood pressure rise during exercise (1). Incremental prognostic value of imaging variables. Numerous studies (19–24) have shown that incremental prognostic information is obtained when variables from stress myocardial perfusion imaging are added to information obtained solely from clinical and ECG stress test variables. Hachamovitch et al. (23) evaluated the incremental prognostic value of technetium-99m (Tc-99m) sestamibi SPECT imaging in 2,200 consecutive patients. When a stepwise Cox proportional hazards model and receiver operating characteristic curve analysis was used, nuclear testing added incremental prognostic value after inclusion of the most predictive clinical and exercise variables (global chi-square 12 for clinical variables, 31 for clinical plus exercise test variables and 169 for clinical plus exercise plus nuclear test variables). Some studies (15) have shown that when clinical, ECG stress test and scintigraphic variables are known, there is little additional prognostic information yielded by addition of coronary angiographic variables, such as the number of vessels with significant stenoses. Furthermore, recent data (23,25,26) have indicated that the extent of inducible hypoperfusion on post-stress SPECT perfusion images provides superior stratification of patients with stable chest pain attributed to known or suspected CAD into low and high risk groups than the Duke treadmill score. Hachamovitch et al. (23) found that in their study of 2,200 patients, 834 of 1,187 with an intermediate risk treadmill score had a normal Tc-99m sestamibi SPECT scan that was associated with a 0.4% rate of death or infarction during follow-up. Of the remaining patients with intermediate risk scores, the event rate was 6.4% and 8.9%, respectively, in patients with mild or severe SPECT defects. Approximately 50% of patients are classified in an intermediate risk category when the Duke treadmill score alone is used for prognostication, leaving the clinician with perhaps greater indecision regarding management strategy than before treadmill test referral (25). Perhaps the most valuable contribution of exercise or pharmacologic stress imaging is its excellent negative predictive value for predicting a low event rate in patients with a normal scan on symptom-limited exercise testing or with vasodilator stress imaging (1,4,27–30). Patients with normal perfusion scans have a ,1.0 cardiac death or nonfatal infarction rate per year, even if angiographic CAD has been demonstrated (31,32). Tl-201 reinjection and defect reversibility. The identification of defect reversibility on stress and 4-h redistribution imaging can be enhanced by either quantitative scan analysis or reinjection of a second dose of Tl-201 at rest after acquisition of the delayed redistribution images (33–39). Application of “reinjection” Tl-201 imaging in the clinical setting has been directed toward improving the detection of viable myocardium in defects that appear to be persistent, suggesting myocardial scar, on stress and redistribution imaging. Dilsizian et al. (34) reported that 87% of myocardial regions showing reversibility after Tl-201 reinjection showed improved regional perfusion and function after coronary angioplasty. Bonow et al. (40) found an 88% concordancy rate between viability assessed on Tl-201 reinjection imaging and positron emission tomographic– fluorine-18 fluorodeoxyglucose evidence for viability in the same patients. To date, scant data exist concerning the value of Tl-201 *Editorials published in Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. From the Cardiovascular Division, Department of Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia. Address for correspondence: Dr. George A. Beller, Cardiovascular Division, Box 158, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908. E-mail: gbeller@virginia.edu. JACC Vol. 31, No. 6 May 1998:1286–9