Renewed Application of an Old Method Improves Detection of Coronary Ischemia: A Higher Standard of Care Richard M. Fleming, MD, Gordon M. Harrington, PhD, Riaz Baqir, MD, Scott Jay, MD, Sridevi Challapalli, MD, Kayla Avery, CNMT, and Jim Green, CNMT The diagnostic utility of traditional nuclear cardiac imaging is enhanced by using modern technology to compare absolute regional radioactive counts at two points in time during stress/stress testing. uclear cardiac imaging began solute radioactive counts—although cardial perfusion measurements fol- in 1927 with the first in a se- the computer software to accomplish lowing a single injection of sestamibi ries of studies by Blumgart this is available. The extra step of to determine ischemia. We compared Nand Yens, which found that quantifying absolute counts allows the results of coronary angiogra- measuring the rate and magnitude of the clinician to better interpret disease phy—used to determine the extent of nuclide transfer from right arm to left by seeing information the computer coronary lumen disease—with (1) arm could diagnose the presence or uses to assign various shades of grey myocardial perfusion imaging (MPI) absence of heart disease.1 This work or color to the image. findings using a redistribution equa- was not only the first nuclear study When applied to multiple images tion we developed (the Fleming- of the heart, but the first description under the same state (namely, five- Harrington equation) to quantify of quantification of disease by using a minutes and 60-minutes poststress), absolute radioactive counts, and (2) Geiger counter. The radioactive tracer quantifiable absolute counts can then results of rest/stress imaging. thallium-201 was introduced in 1975, be compared using today’s single pho- followed by contemporary tracers, ton emission computed tomography BACKGROUND such as technetium-99m sestamibi. (SPECT) cameras. Using these cam- In 1959, Gorlin demonstrated that Many studies have shown that eras, the clinician can look for the resting images were not diagnosti- knowledge of sestamibi redistribu- actual change in isotope concentra- cally useful for ischemia and should tion, as revealed by sequential stress tion that results from various levels of not be used for this purpose.8 Fur- imaging, improves detection of heart ischemia—caused by differences in a ther discussions by Love questioned disease.2–6 While these studies quanti- coronary artery’s ability to vasodilate whether nuclear imaging would fied sestamibi differences in heart to to meet coronary blood flow demands ever be clinically useful due to the lung ratios, they did not quantify ab- and coronary artery blockage (Figure absence of clinically useable iso- 1)7. This clinical information is diag- topes.9 Although the introduction of Dr. Fleming, Dr. Jay, and Ms. Avery are all cardi- nostically important and allows the thallium-201 partially allayed those ologists at the Cardiovascular Institute of South- primary care physician to determine fears, the tracer was plagued with a ern Missouri, Poplar Bluffs, MO. Dr. Harrington is a professor in the department of psychology at whether medical management or an long half-life of 72 hours. None- the University of Northern Iowa, Cedar Falls, IA. invasive cardiac procedure is the next theless, thallium-201 was clinically Dr. Baqir is a cardiologist in the division of cardi- best step in caring for the patient. useable for detecting ischemia by ology at the VA Central Iowa Health Care System (VACIHCS), Des Moines, IA. Dr. Challapalli and To demonstrate the advantages of qualitatively evaluating two post- Mr. Green are both cardiologists at the Sierra Ne- obtaining absolute radioactive counts stress images (at one and four hours). vada Cardiology Associates (SNCA), Reno, NV. In in sequential stress imaging, we de- The unfortunate use of the terms addition, Dr. Fleming is a cardiologist at the SNCA 10 and was a cardiologist in the division of cardiol- signed a study to assess the clinical “stress” and “rest,” however, re- ogy at the VACIHCS. diagnostic utility of time-course myo- sulted in a misunderstanding of the 22 • FEDERAL PRACTITIONER • JUNE 2010 established principles laid out by Blumgart and Yens—that compari- sons should be made under same- state conditions, either stress or rest. Maublant and Crane demonstrated that use of sestamibi had a washout of 28 minutes and that this washout Joe Gorman © 2010. increases under ischemic conditions because of mitochondrial calcium overload; the clinical importance of this finding had been underrecog- nized previously.11,12 Nuclear MPI using SPECT for the detection of ischemia is accomplished by comparing two images of the heart obtained at two points in time. While Blumgart emphasized comparisons under same-state conditions, clini- cians since have emphasized rest/ stress comparisons. The resting image more correctly can be used to determine if myocardial injury has occurred previously, but cannot be utilized to determine if ischemia is present.1,8 Nonetheless, most diagnosticians today compare the rest to stress im- ages and conclude that when the images have identical findings (matching defects) no ischemia is present. However, injury/infarction noted on the resting image in the ab- sence of ischemia (stress image) is in- consistent with the disease process as we know it, and matching defects hours but not after two hours.14,15 ter with today’s SPECT camera to clearly cannot mean that a region of The presence or absence of washin compare radioactive counts, both infarction has no ischemia; rather, it was attributed to cell viability and quantitatively and qualitatively, merely means that the infarction is thus, differentiated ischemia with in- has increased the diagnostic accu- the result of ischemia. In other words, farcted tissue (matched defects) from racy of detecting congestive heart one cannot have myocardial infarc- ischemia with viable tissue (non- failure, cardiomyopathy, coronary tion in the absence of an underlying matched defects). Most clinicians vasospasm, and, as our initial stud- ischemic insult to the region. There- treat contemporary tracers, such as ies established, the relationship fore, matching rest/stress images de- sestamibi, as though they do not un- between “inflammation” and coro- fine ischemia present at the site of dergo redistribution (washin or wash- nary artery disease.2–5,17–25 In recent injury/infarction and not a simplistic out), despite ample evidence to the work, we have better defined the re- absence of ischemia.13 contrary, including a recent investiga- lationship between sestamibi redis- Much controversy followed the tion by Fallahi and Beiki.2–6,10,12,16 tribution and the extent of actual institution of sequential stress imag- Recent research utilizing knowl- coronary artery disease seen in the ing, which found instances of redis- edge of sestamibi redistribution and angiography suite—yielding substan- tribution with thallium-201 after four replacing Blumgart’s Geiger coun- tially increased diagnostic accuracy in JUNE 2010 • FEDERAL PRACTITIONER • 23 DETECTION OF CORONARy IsChEmIA the stress component of the study where they underwent either exercise (treadmill) or pharmacologic stress. Following standard protocols already described in the medical and scien- tific literature, we injected intrave- nously a bolus of sestamibi (28 to 32 mCi, 1036 to 1184 MBq) followed by a bolus of normal saline to ensure adequate delivery of the radioactive isotope into the venous system. Five minutes following delivery of sesta- mibi, a SPECT camera was used to obtain a five-minute image (anterior slice, single-head camera) or images (anterior and lateral slices, multiple- Coronary (stenosis) flow reserve Coronary head camera). Fifty-five minutes later (60-minutes poststress), participants returned to the lab for final images. Cummulative percent narrowing (blue = %DS, red = %ASa) DAtA COlleCtION AND Figure 1.7 Relationship between stenosis flow reserve and percent diameter stenosis ANAlySIS (%DS), demonstrating that as arteries become more critically narrowed they are less able to vasodilate upon demand, requiring a longer time to achieve isotope equilibrium. Image comparisons and a%AS = percent area stenosis. redistribution calculations We evaluated rest/stress images using visual, qualitative slice-to-slice com- the detection and evaluation of coro- Patients arrived at the nuclear lab- parisons. For the redistribution cal- nary ischemia.26,27 The study we pres- oratory in a fasting state according culation, we drew regions of interest ent here is a follow-up to our most to each institution’s approved proto- (ROIs) using the five-minute post- recent work measuring sestamibi cols for MPI. Specific institutional re- stress images to quantify radioactive redistribution and comparing the view board (IRB) requirements were counts, including total heart and findings with results from coronary reviewed. Patients underwent addi- lung, basal and mid anterior, basal angiography and rest/stress images.28 tional imaging, but they did not re- and mid anterolateral, basal and mid ceive further injections of radioactive inferior-posterior, and basal and mid StUDy DeSIGN AND materials nor were they placed under inferoseptal regions (Figure 3). We PARticipantS additional exercise or pharmacologic avoided the issue of cardiac creep (a We studied 120 men and women “stress”; thus, the additional acqui- form of gradual internal heart mo- (aged 25 to 82 years) suspected of sition of redistribution