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Nuclear Cardiology: Where Do We Stand? (3) Daniel S. Berman, MD| Introduction - Myocardial perfusion assessment (1) |
| Ventricular function assessment (2) |
| Future directions - References (3) |
Future Directions
We need broader use of defect extent and severity variables, broader use of objective quantitative analysis, incorporation of ventricular function information, and better incorporation of clinical variables. Now, beyond just looking at diagnosis and risk stratification, we should be considering using our technology for evaluating patients over time, assessing therapy. As John Mahmarian’s group has shown, if you take patients following myocardial infarction, and you place them on medical therapy or give them coronary angioplasty, there are a group of people with large defects who actually show an improvement over a brief period in myocardial perfusion extent and severity with medical therapy as well as with angioplasty (Figure 19). Those patients appear to do as well as the patients who are given the more aggressive angioplasty approach. I think we are going to see this early evaluation of therapy expanding our impact in nuclear cardiology patient management. Furthermore, we are seeing a much broader use of these nuclear techniques in randomized clinical trials.
Fig. 19: Mean and individual patient changes in PDS from SPECT 1 to 2. Bold
lines indicate
patients who reduced their PDS by ³ 9%. Circled dots indicate patients who had a
recurrent
event. (Adapted with permission from Circulation 1998; 201(7):2023)
For the long-term future, we are in part dependent on our industry colleagues. Because we have not yet developed the ideal perfusion tracer, the future of our perfusion and viability methods are really dependent on how they take us forward over the next ten years. The ideal agent should be a technetium label for Anger camera imaging, have 100% extraction across the spectrum of achievable flow, something that we are not really close to with any of the current perfusion tracers. There should be instantaneous intracellular binding so there is no washout or redistribution, allowing us to have the flexibility to image the patient again, if we happen to have movement or some other process that stops our ability to get an accurate answer from the first image sequence. There should be low clearance or extraction by organs adjacent to the heart, so we can have adequate myocardial imaging and we should have myocardial extraction only by viable cells.
How do the current tracers measure to this ideal standard? (Figure 20) Oxygen-15 labeled water is extracted across the range of flow, but it’s a PET scanning agent with very poor imaging characteristics because it requires a blood pool subtraction method. It’s the only agent with this linear relationship between myocardial tracers uptake and flow across the spectrum of flow. Everything else falls short. Thallium is an excellent tracer, but doesn’t have very good physical characteristics and doesn’t stay in one spot – there is no intracellular binding, so one has to image right away and get the imaging right on the first occasion. All of the other agents fall short of thallium with respect to extraction, with the possibile exception of teboroxine which washes out faster than thallium-201 and is more difficult to use. I’d like to see the industry helping us by getting an agent closer to ideal. It would also be helpful, if we can, in conjunction with industry, develop accurate motion correction algorithms. Significant patient motion, causing perfusion defects, probably occurs in 5% to 10% of patients undergoing myocardial perfusion. SPECT improved table design would be important in this regard and is likely to be forthcoming from manufacturers. And then motion correction algorithms (Table 5) or repeat imaging in the prone position (Figure 5) should be thought of in terms of decreasing motion artifacts (Figure 21). Attenuation scatter and resolution recovery are other areas in which SPECT can improve (Table 6). The requirements should be a complete attenuation correction without loss of defect contrast or introduction of artifacts. There should be no gender differences in observed tracer concentrations and the approach should provide higher sensitivity and specificity. The key components would be a high quality attenuation map and accurate scatter correction as well as resolution recovery. I think we are going to see our technology moving in that direction with time. Finally, we ought to take advantage of the potential of being able to do simultaneous imaging with thallium and with a technetium labeled agent so that we could cut in half our imaging time (Figure 22). Beyond perfusion we shouldn’t loose track of the fact that iodine-123 is almost as good as technetium-99m in being a mono-energetic gamma emission with a good energy for Anger camera imaging and relatively short half-life (Table 7, Table 8). It just hasn’t become commercially available on a regular basis, at a cheap enough cost. If we had iodine-123, we could talk in our field beyond perfusion into looking at myocardial innervation with MIBG which has already been shown to have promising application in heart failure. We could be looking at fatty acid metabolism with BMIPP with its interesting ischemic memory which might allow us to take patients who present after their chest pain and see whether that was related to myocardial ischemia. And then finally we could become able to look at unstable plaque, potentially by looking at unstable plaque components.
Fig. 20: Diagrammatic illustration of the theoretical
relationship between myocardial tracer uptake and
myocardial bloodflow for the available
radiopharmaceuticals
Fig. 21: Supine (top) and prone (bottom) exercise technetium-99m
sestamibi SPECT images in
a 55-year-old male patient, demonstrating an inferior wall defect on the supine study
which is not
seen on the prone images. On the basis of the combined images, the myocardial perfusion
SPECT
examination was interpreted as normal.
Table 6: Attenuation/Scatter/Resolution Correction
Fig. 22: Simultaneous dual isotope myocardial perfusion SPECT. Until
background subtraction techniques
are developed, this protocol is not recommended. (Adapted with permission from JNM 1994;
35: 681-688)
Table 8: Promising current cardiac applications of I-123 labeled compounds.
1. Germano G, Kiat H, Kavanagh, PB, et al. Automatic quantification of
ejection fraction from gated myocardial perfusion SPECT. J Nucl Med, 1995. 36(11): p.
2138-47.
2. Germano G, Berman DS, eds. Clinical Gated Cardiac SPECT, Futura Publishing Co, Armonk,
NY, 1999. Chapter 4: p 115.
3. Berman DS, Hachamovitch R. Risk assessment in patients with stable coronary artery
disease: Incremental value of nuclear imaging. J Nucl Cardiol 1996;3:S41-S49.
4. Berman DS, Kiat H, Friedman JD, Diamond GA. Clinical applications of exercise Nuclear
Cardiology Studies in the era of healthcare reform. Am J Cardiol 1995;75:3D-13D.
5. The Bypass Angioplasty Revascularization Investigation (BARI) Investigators. Comparison
of coronary bypass surgery with angioplasty in patients with multivessel disease. N Eng J
Med 1996;335:217-25
6. Berman DS, Hachamovitch R, Kiat H, et al. Incremental value of prognostic testing in
patients with known or suspected ischemic heart disease: A basis for optimal utilization
of exercise technetium-99m sestamibi myocardial perfusion single-photon emission computed
tomography. J Am Coll Cardiol 1995;26:639-47.
7. Hachamovitch R, Berman DS, Kiat H, et al. Effective risk stratification using exercise
myocardial perfusion SPECT in women: Gender-related differences in prognostic testing. J
Am Coll Cardiol 1996; 28:34-44.
8. Hachamovitch R, Berman DS, Kiat H, et al. Exercise myocardial perfusion SPECT in
patients without known coronary artery disease: Incremental prognostic value and use in
risk stratification. Circulation 1996;93:905-14.
9. Bateman TM, O’Keefe JH, Dong VM, et al. Coronary angiographic rates after stress
single-photon emission computed tomographic scintigraphy. J Nucle Cardiol 1995;2:217-23.
10. Nallamothu N, Pancholy SB, Lee KR, Heo J, Iskandrian, AS. Impact on exercise
single-photon emission computed tomographic thallium imaging on patient management and
outcome. J Nucl Cardiol 1995;2:334-8.
11. Amanullah AM, Kiat H, Hachamovitch R, Cabico JA, Cohen I, Friedman JD, Berman DS.
Impact of myocardial perfusion single-photon emission computed tomography on referral to
catheterization of the very elderly: Is there evidence of gender-related referral bias? J
Am Coll Cardiol 1996;28:680-686
12. Hachamovitch R, Berman DS, Shaw LJ, Kiat H, Cohen I, Cabico JA, Friedman JD, Diamond
GA. Incremental prognostic value of myocardial perfusion SPECT for the prediction of
cardiac death: Differential stratification for risk of cardiac death and myocardial
infarction. Circulation 1998;97:535-543
13. Hachamovitch R, Berman D, Kiat H, Cohen I, Cabico A, Diamond G. What is the warranty
for normal exercise sestamibi SPECT? Circulation 1995;92:1-52
14. Shaw LJ, Hachamovitch R, Marwick Th, Heller GV, Berman DS. Cost-effectiveness analysis
of stress myocardial perfusion imaging in stable angina patients: Influence of age and
pretest risk of coronary disease. JACC: In press, 1999
15. Topol EJ. Coronary angioplasty for acute myocardial infarction. Annals of Internal
Medicine 1988:109;970-80
16. Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) Trial
Investigators. Outcomes in patients with acute non-Q—wave myocardial infarction
randomly assigned to an invasive as compared with a conservative management strategy. N
Engl J Med 1998; 338:1785-92
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