Clinical Significance of Reverse Redistribution in Thallium Scintigraphy

Joint Program in Nuclear Medicine

Richard C. Hom, MD, PhD

David E. Drum, MD, PhD

April 26, 1994

Case Presentation:

Case 1:

A 74 year old man with a history of coronary artery disease presented for a pre operative evaluation of myocardial perfusion by exercise Tl-201 scintigraphy (17k bytes). (Vertical long axis views; top row shows stress images; bottom row shows redistribution images.)

Case 2:

A 74 year old man with a history of coronary artery disease presented for risk stratification by dipyridamole Tl-201 scintigraphy (14k bytes). (Vertical long axis views; top row shows stress images; bottom row shows redistribution images.)

Findings:

There is reverse redistribution in the inferior wall in both Case 1 (arrow, 17k bytes) and Case 2 (arrow, 15k bytes)

Discussion:

It was noted in the early 1980s (Hecht), in a review of over 300 consecutive exercise and redistribution studies performed in the evaluation of chest pain, that 7% of the Tl-201 studies had reverse redistribution (RR), defined as a normal exercise perfusion with a defect on redistribution, or an exercise defect worsened at redistribution. Of the 15 patients with coronary artery disease (CAD) demonstrated by cardiac catheterization, 17 of 20 RR defects were found in the distribution of severely diseased vessels (>90% occlusion). However, more than half of the RR defects were supplied either by collateral vessels or by bypass grafts. Ventriculography revealed abnormally contracting segments in 14/18 (78%) of those studied. In an even larger series, Silberstein and DeVries (1985) found 35 (5%) among 785 consecutive Tl-201-exercise studies. Twenty of these patients underwent coronary angiography; 11 had stenoses of at least 50% and 9 were judged to have no significant coronary artery stenosis. 5 of the 11 patients with RR had the least severe stenosis in the vessels supplying the regions of RR. In addition, the location of the RR was predictive in only 45% of the cases. Popma et al found that RR occurred in 7% of the 250 myocardial segments analyzed in 90 men in dipyridamole- Tl-201 SPECT studies performed for angina pectoris. Furthermore, they found that coronary artery stenosis did not differ between those regions with normal perfusion from those with reverse redistribution, suggesting that the presence of RR was not necessarily associated with severe CAD.

Patients with Acute Myocardial Infarction Treated with PTCA or Thrombolysis

Weiss et al (1986) noted that RR (in the 4 hour resting images compared with the immediate post injection image on day 10) occurred in 50/67 (75%) patients with evolving myocardial infarction who had undergone early streptokinase therapy. The RR was associated with patency of the infarction-related artery in 100% of the patients with RR, who also had quantitative improvement in the resting Tl-201 defect sizes (94% of the segments) from day 1 to day 10. In addition, 80% of the cardiac segments on RVG had normal (or near normal) wall motion on day 10. The group with RR was the same as the group with the normal scans or having a reversible defect with respect to patency of the involved coronary artery and RVG wall motion. In contrast, patients found to have fixed defects, 67% (4/6) had patent coronary arteries in the region of the infarction; only 21% of the wall segments had normal wall motion on RVG. This study implied that RR is caused by faster than normal Tl-201 washout in the reperfused region and may be a sign of reopening of the occluded coronary artery with the presence of viable myocardium in the reperfused zone. Fukuzawa and coworkers (1992) looked at RR in 61 patients who successfully underwent reperfusion (out of 68 patients) with tissue plasminogen activator (TPA), PTCA, or both TPA and PTCA (because of persistent anginal pain) and found RR in 19 patients when studied under submaximal stress 3 weeks later. The degree of residual stenosis after reperfusion in patients with RR was less than 50% versus >90% in 11/12 patients with redistribution and >75% in 12/30 patients with nonreversible defects. Regional wall motion of all of the 19 patients were normal or near normal in the affected walls. Twelve months later, 12 of these patients still had a smaller area of RR or a normal pattern. Thus, this study extended the study by Weiss and coworkers by the use of the submaximal stress test and SPECT imaging, and also suggested that RR indicates improvement in regional function with a good prognosis following reperfusion therapy for an acute myocardial infarction.

Patients with Acute Myocardial Infarction NOT Treated with PTCA or Thrombolysis

Yamagishi and coworkers performed one or two Tl-201 SPECT studies on 80 patients at 1 week to 2 months post-MI and found that 38 (48%) patients had RR in at least one study. Inferior wall infarction occurred in the group with RR 66% of the time compared with patients with fixed defects who had infarction in the same area 19% of the time. The group with RR also had milder wall motion abnormality on 2D-Echo than the group with fixed defects. Of the 16 patients with RR who underwent the study twice, 5 demonstrated a fixed defect on the second study while 11 had persistent RR. The former group had improvement in the wall motion between the acute phase and the subacute phase post-MI.

Chronic Stable Coronary Artery Disease

The presence of viable myocardium in chronic stable coronary artery disease in regions of RR was found by Marin-Neto and colleagues (1993) by the use of thallium reinjection in 39 patients with SPECT imaging after the 4 hour rest images were obtained. Of the 39 regions with RR, 82% (32) showed enhanced Tl-201 activity after reinjection. Q waves were seen in only 25% of the regions with enhanced Tl-201 uptake after reinjection vs. 71% not responding to reinjection. Wall motion study showed akinesis/dyskinesis in only 9% of the 32 regions with enhanced Tl-201 reinjection uptake. Critically stenosed or totally occluded coronary arteries supplying 24/29 (83%) regions of enhanced Tl-201 uptake after reinjection were seen. Collateral circulation was detected in 23/29 (79%) of regions with a positive thallium reinjection but in only 1/7 of the regions without change from reinjection. Therefore, they concluded that RR in chronic coronary artery disease reflects the presence of viable myocardium which is dependent on collateral circulation. Similarly, Pace (1993) in Italy found that in patients with chronic CAD, LV dysfunction with a history of a previous MI, heart segments with RR in which Tl-201 uptake was normal at rest but abnormal on redistribution, when compared with normal heart segments, had a higher degree of coronary artery stenosis, worse LV wall motion and decreased MIBI uptake.

Theories on the Mechanism of RR

1) Increased Tl-201 washout from a) higher local blood flow at rest or b) inability of the myocardium to hold onto the Tl-201.

2) Hibernating or stunned myocardium mixed with scarring, so that the involved tissues can receive the initial Tl-201 but cannot hold onto it effectively. This is consistent with Weiss' results described above along with those of Silberstein and DeVries. Again, in Pace's study, the idea of a stunned/hibernating myocardium (a result from previous coronary artery occlusions) supported by a lower MIBI uptake may explain the presence of RR associated with occluded but well collateralized coronary circulation.

3) Recruitment of collaterals at stress.

References:

1. Hecht, HS, Hopkins, JM, Rose, JG, Blumfield, BE, and Wong, M. Reverse redistribution: Worsening of Thallium-201 myocardial images from exercise to redistribution. Radiology 140:177-181 (1981).

2. Silberstein, EB and DeVries, DF. Reverse redistribution phenomenon in Thallium-201 stress tests: Angiographic correlation and clinical significance. J. Nucl. Med. 26:707-710 (1985).

3. Weiss, AT, Maddahi, J, Lew, AS, Shah, PK, Ganz, W, Swan, HJC, and Berman, DS. Reverse redistribution of Thallium-201: A sign of nontransmural myocardial infarction with patency of the infarct-related coronary artery. J. Am. Coll. Cardiol. 7:61-7 (1986).

4. Lear, JL, Raff, U, and Jain, R. Reverse and pseudo redistribution of Thallium-201 in healed myocardial infarction and normal and negative thallium-201 washout in ischemia due to background oversubtraction. Am. J. Cardiol. 62:543-550 (1988).

5. Popma, JJ, Smitherman, TC, Walker, BS, Simon, TR, and Dehmer, GJ. Reverse redistribution of Thallium-201 detected by SPECT imaging after Dipyridamole in angina pectoris. Am. J. Cardiol 65:1176-1180 (1990).

6. Yamagishi, H, Itagane, H, Akioka, K, et al. Clinical significance of reverse redistribution on Thallium-201 single-photon emission computed tomography in patients with acute myocardial infarction. Jpn. Circ. J. 56:1095-1105 (1992).

7. Fukuzawa, S, Ozawa, S, Nobuyoshi, M and Inagaki, Y. Reverse redistribution on Tl-201 SPECT images after reperfusion therapy for acute myocardial infarcion: Possible mechanism and prognostic implications. Heart Vessels 7:141-147 (1992).

8. Pace, L, Cuocolo, A, Maurea, S, et al. Reverse redistribution in resting Thallium-201 myocardial scintigraphy in patients with coronary artery disease: Relation to coronary anatomy and ventricular function. J. Nucl. Med. 34:1688-1692 (1993).

9. Liu, P, and Burns, RJ. Easy come, easy go: Time to pause and put thallium reverse redistribution in perspective. J. Nucl. Med. 34: 1692-4 (1993).

10. Marin-Neto, JA, Dilsizian, V, Arrighi, JA, Freedman, NMT, Perrone-Filardi, P, Bacharach, SL, and Bonow, RO. Thallium reinjection demonstrates viable myocardium in regions with reverse redistribution. Circulation. 88[part 1]: 1736-1745 (1993).

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J. Anthony Parker, MD PhD, Tony_Parker@bih.harvard.edu