Assessment of myocardial viability by nuclear imaging in coronary heart disease

INTRODUCTION — Coronary heart disease (CHD) is the major cause of heart failure [1]. In the past, severe left ventricular (LV) dysfunction was considered an irreversible condition, as regional akinesis was thought to represent infarcted myocardial tissue. It is now understood that, among patients with ischemic cardiomyopathy, LV systolic dysfunction can result from myocardial necrosis and remodeling, myocardial hibernation, or repetitive myocardial stunning. While myocardial necrosis is irreversible, systolic dysfunction resulting from hibernation and stunning are potentially reversible states of ventricular dysfunction. (See "Pathophysiology of stunned or hibernating myocardium".)

Most patients with chronic heart failure have an admixture of all three pathophysiologic entities [2]. Clinical studies have shown that viable myocardium can be demonstrated in a substantial number of patients with CHD and LV dysfunction, even in the absence of angina [2-5]. In patients with significant amounts of viable myocardium, LV function may improve markedly, and even normalize, following successful revascularization (figure 1) [6-8]. An estimated 20 to 40 percent of patients with chronic ischemic LV dysfunction have the potential for significant improvement in LV function after revascularization [9]. (See "Evaluation of hibernating myocardium" and "Treatment of ischemic cardiomyopathy".)

The outcome following revascularization is dependent not only on the presence but also the extent of viability, and a critical threshold mass of viable myocardium may be necessary for functional recovery and prognostic benefit to occur from revascularization [10-13]. Therefore, while several clinical and laboratory parameters including anginal symptoms, absence of Q waves on the electrocardiogram, and regional hypokinesis (as opposed to akinesis) on echocardiography indicate the presence of some viability, a systematic assessment of the degree and extent of viability by myocardial imaging is generally thought to be helpful for management planning and prognostication.

To the extent that improvement in regional or global LV function, and thereby prognosis, is a significant goal in such patients, the ability to accurately assess regional myocardial viability in a dysfunctional territory prior to revascularization becomes an important component of the decision-making process. The most commonly used radionuclide imaging techniques for assessing myocardial viability in this setting will be reviewed here (figure 2). The use of cardiac magnetic resonance imaging and dobutamine echocardiography for assessing myocardial viability is discussed separately. (See "Dobutamine stress echocardiography in the evaluation of hibernating myocardium" and "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Myocardial viability'.)

TECHNIQUES FOR ASSESSING MYOCARDIAL VIABILITY

Thallium-201 radionuclide myocardial perfusion imaging — Thallium-201 was introduced as a perfusion tracer because of its high (approximately 80 percent) first pass myocardial extraction fraction across physiologic ranges of myocardial blood flow [14]. The myocardial uptake of thallium-201 is a sarcolemmal membrane Na/K ATPase-dependent active process requiring cell membrane integrity, and is therefore indicative of myocardial viability. Thallium-201 uptake by myocytes is also a reflection of regional perfusion (required for delivery of tracer to the myocyte) and viability. (See "Basic properties of myocardial perfusion agents".)

Several different approaches have been employed to optimize the information obtained from thallium-201 imaging. The table lists the various protocols that have been used for viability assessment (table 1).

Stress-redistribution imaging — In 1977, it was reported that some stress-induced thallium defects could normalize or "redistribute" on serial images repeated several hours later [15]. It was proposed that regional thallium redistribution activity represented the extent of regional myocardial viability. As a result, stress-redistribution thallium imaging following a single stress injection became the standard imaging protocol for assessing the presence of coronary disease and the extent of inducible ischemia.

The demonstration of reversible ischemia by the conventional protocol (immediate stress imaging followed by four-hour redistribution imaging) implies the presence of viable myocardium. However, up to 47 percent of segments that have fixed defects at four hours show evidence of viability on PET scanning [11] or recover either perfusion or function following revascularization [16-18]. Therefore, several modifications of the stress-4 hour redistribution protocol were developed to improve the accuracy of viability detection.

Late redistribution imaging — In some instances, the redistribution of thallium-201 appears to take longer than the four hours allowed in standard stress-redistribution protocols. This variability may reflect relatively lower blood levels of thallium-201 throughout the redistribution period, thereby reducing thallium-201 input over time into severely ischemic areas [19].

This observation led to the development of late redistribution protocols, which generally involve redistribution imaging 18 to 24 hours after thallium-201 injection. With these protocols, thallium-201 redistribution is seen in a significant number of perfusion defects deemed fixed by imaging at four hours [20-23]. In one study, for example, late distribution at 24 hours occurred in one-fifth of defects thought to be fixed by conventional four-hour imaging [24].

Late redistribution has been validated as an accurate predictor of viability, with up to 95 percent of segments with late redistribution showing improved stress perfusion following revascularization [23]. However, even with delayed imaging, a proportion of segments with fixed defects improve function after revascularization, suggesting that some viable segments may never redistribute unless blood levels of thallium-201 are augmented [9]. In one study, 37 percent of segments labeled as fixed defects even after late imaging improved perfusion after revascularization [23].

Thus, the presence of thallium-201 uptake at late redistribution is an accurate marker of regional viability while its absence may underestimate viable myocardial tissue to a significant degree. Late redistribution imaging may also result in images of poor quality due to tracer washout and decay, and it is also an inconvenience for patients having to return on a subsequent day.

Thallium-201 reinjection protocols — The reinjection of a second, smaller dose of thallium-201 immediately following the redistribution images increases the blood level of thallium-201, and may circumvent some of the problems associated with redistribution imaging, resulting in enhanced detection of stress defect reversibility [25]. This method has been shown to identify viable territories in as many as 50 to 70 percent of regions which were deemed to be scar by standard three- to four-hour redistribution [26-28]. Additional delayed imaging does not appear to improve sensitivity of viability detection with this protocol, which has positive and negative predictive values of 69 percent and 89 percent, respectively, thus indicating good sensitivity and modest specificity [25,26,29].

Rest-redistribution imaging — Since thallium-201 was initially thought of as a blood flow tracer, a defect seen on an image taken soon after a rest injection of thallium-201 was assumed to be associated with regional infarction. However, a significant percentage of resting thallium-201 defects show redistribution when reimaged several hours after injection [30,31]. Segments which show a reversible resting thallium-201 defect often have improved perfusion after revascularization, suggesting that this finding is indicative of regional myocardial viability [31]. An increase of tracer uptake of 10 percent or more on the redistribution images is usually considered indicative of viability in this setting. In contrast to stress-redistribution thallium-201 protocol for viability assessment, a four-hour redistribution protocol is generally adequate after a resting injection of thallium-201. More delayed rest-redistribution imaging has not been found to improve viability detection.

Rest-redistribution imaging is useful when viability information is required after a dual isotope rest-stress study has demonstrated an apparently fixed perfusion defect. In dual isotope protocols, a rest thallium-201 study is followed by a stress study with either technetium Tc-99m sestamibi or technetium Tc-99m tetrofosmin. This has the advantage of a shorter overall study time compared with a single-isotope (ie, Tc-99m based tracer only) rest-stress study. When a fixed defect is encountered on a dual isotope study, the patient can be brought back the next day for delayed thallium-201 imaging for viability assessment. At this time, Tc-99m, which has a half-life of around six hours, is no longer present in the myocardium. Notably, dual isotope protocols are not used commonly or recommended for stress imaging because of the relatively higher radiation dose to patients.

Quantitation — Quantitation of thallium-201 uptake on redistribution images further improves the prediction of viability, with higher counts being more reliably predictive of improvement in regional perfusion and/or function after revascularization [10]. The quantitation of relative regional thallium-201 activity in rest-redistribution studies is generally highly concordant with findings from stress-redistribution-reinjection imaging [32]. Viability assessment based on quantification of thallium-201 uptake more accurately predicts improvement in perfusion or function after revascularization than a dichotomous visual analysis of the presence or absence of stress defect reversibility.

Quantitative techniques may be of particular utility in segments that appear on inspection to have fixed defects. In such segments, significant thallium-201 uptake may still be present. The presence of thallium uptake >50 percent to 60 percent of that in normal segments is indicative of the presence of viable myocardium as demonstrated in comparative studies with PET imaging [33]. One report, for example, evaluated a group of patients with planar thallium-201 stress-redistribution imaging: 45 percent of fixed thallium-201 defects preoperatively showed improved thallium-201 uptake following bypass grafting [18]. However, with the use of quantitative analysis of the magnitude of thallium-201 uptake within these fixed defects, stratification of segments into those more or less likely to improve perfusion after revascularization was achieved.

In general however, fixed defects, even mild ones, are less likely to improve resting function following revascularization than reversible defects because this pattern may be seen both in "transmurally hibernating" segments, which have a high likelihood of functional recovery after revascularization, and in segments with subendocardial necrosis with retained epicardial viability, which are far less likely to improve resting function after revascularization [10,34]. Thus, the use of quantitation to define a "cut-off" threshold for viability (usually 50 to 60 percent of activity in the normal segments) may not accurately reflect the likelihood of myocardial recovery.

Instead, it may be more effective to use quantitative methods to define a probability of recovery. There appears to be a continuous relationship between the amount of tracer uptake and the likelihood of functional recovery after revascularization. In one study, 56 percent of segments with 50 to 60 percent uptake and 88 percent of segments with greater than 80 percent uptake of thallium-201 improved after revascularization [24].

Nitrate enhanced imaging — In patients who can tolerate sublingual nitroglycerin (SL NTG), some centers give SL NTG five minutes before the administration of tracer. This approach may increase the accuracy of the study, but practice varies between centers, with some centers routinely giving SL NTG and other centers rarely giving it.

The rationale for giving SL NTG is to increase the sensitivity and specificity of the viability study. Nitrate administration enhances the flow to peri-infarct regions and improves thallium-201 delivery to myocytes. One study compared a nitrate enhanced rest thallium-201 perfusion scan with conventional exercise and four-hour redistribution thallium-201 imaging in 100 patients, six weeks after a myocardial infarction and thrombolytic therapy [35]. The non-nitrate enhanced protocol demonstrated reversible ischemia in 29 patients; the incidence of cardiac events was similar in those with and without a reversible defect (48 versus 32 percent, p = NS) after a 21-month follow-up. In comparison, a nitrate enhanced thallium-201 scan detected a "reversible" defect in 68 patients. A cardiac event occurred significantly more often in those with a reversible defect than in those without such a defect (49 versus 13 percent, hazard ratio 8).

Summary — The use of thallium-201 radionuclide myocardial perfusion imaging for viability detection can be summarized as follows:

●With stress imaging protocols, the finding of stress defect reversibility (inducible ischemia) on redistribution or reinjection images strongly implies the presence of ischemic, viable myocardium, and a high likelihood for functional improvement of a resting wall motion abnormality in that territory.

●The finding of a fixed thallium-201 defect of only mild-to-moderate severity using quantitative methods implies the presence of a degree of viable tissue. However, dysfunctional segments demonstrating this pattern probably have only a moderate chance of functional recovery.

●The finding of a fixed defect with a severe reduction in thallium-201 activity in stress-redistribution-reinjection protocols or rest-redistribution protocols implies a high likelihood of predominantly nonviable myocardium. In most studies, there is a 10 to 25 percent incidence of functional recovery following revascularization in such territories, a figure similar to that seen when PET imaging identifies a territory as predominantly nonviable.

SPECT IMAGING WITH TC-99M LABELED RADIOTRACERS — Technetium-99m (Tc-99m) sestamibi, a lipophilic cationic compound, and Tc-99m tetrofosmin, a diphosphine agent, are Tc-99m labeled radiotracers; their uptake across myocyte cell membranes is by passive diffusion, in contrast to the active uptake of thallium-201. The uptake and retention of these compounds within myocytes depends upon the presence of intact electrochemical gradients across sarcolemmal and mitochondrial membranes [36,37]. The technetium label imparts better gamma camera imaging characteristics to these agents compared with thallium-201, and their myocardial uptake generally parallels myocardial perfusion [37]. A significant difference from thallium-201 is that these agents show minimal redistribution within the myocardium [38-40]. (See "Basic properties of myocardial perfusion agents".)

The passive nature of Tc-99m sestamibi uptake by myocytes and its relative lack of redistribution within the myocardium were initially perceived as properties that would hinder the use of Tc-99m sestamibi for viability assessment. However, the uptake and retention of this agent requires the presence of intact sarcolemmal and mitochondrial membranes, making it conceptually a good tracer of regional cellular viability. It was also thought that the absence of significant myocardial redistribution would result in underestimation of viability in areas with severe resting hypoperfusion (and therefore, poor initial tracer uptake). This, again, has proven to be a largely theoretical concern.

Comparison of thallium and technetium imaging — Studies comparing viability detection with thallium-201 and Tc-99m sestamibi have generally demonstrated good agreement between these agents, both in the amount of their uptake into areas of viable myocardium (the resting Tc-99m sestamibi image correlating with the thallium-201 redistribution or reinjection image), and also in their ability to predict recovery of function following revascularization.

●One report evaluated an animal model of short-term low-flow ischemia that was accompanied by regional dysfunction without infarction [40]. Thallium-201 and Tc-99m sestamibi were injected at rest, with counting of regional tracer activity three hours after injection. Contrary to the expectation of higher thallium-201 activity at this time point, thallium-201 and Tc-99m sestamibi activities were equivalent across all levels of reduced flow (as determined by radioactive microspheres). Thus, the kinetics of Tc-99m sestamibi (and of thallium-201) under low-flow conditions is more complex than can be explained by a simple flow-dependent model.

●A study in humans used quantitative techniques after resting thallium-201 and Tc-99m sestamibi injections [41]. Among dyssynergic segments, those with reversible dysfunction following revascularization had similar relative regional activities of thallium-201 (at redistribution) and Tc-99m sestamibi. Activities within persistently dysfunctional segments were also similar, and the sensitivity and specificity for identifying improved regional wall motion were not statistically different.

●Another study found analogous results using single-photon emission computed tomography (SPECT) imaging in patients with LV dysfunction [34]. Thallium-201 (at redistribution after rest injection) and Tc-99m sestamibi activities were similar in both reversibly and persistently dysfunctional myocardium, and both isotopes had equivalent positive and negative predictive values for identifying reversible dysfunction. There also was a general correlation between the relative magnitude of isotope uptake (using either thallium-201 or Tc-99m sestamibi) and the probability of regional viability. Segments with well-preserved regional uptake had a very high likelihood of being viable by wall motion criteria; segments with moderately reduced levels of isotope uptake had a moderate probability; and segments with severe reductions in isotope activity had a low probability of being viable. Similar results have been reported in comparative studies of Tc-99m sestamibi with PET imaging [42].

●The use of nitrates in conjunction with Tc-99m sestamibi has been shown to improve its ability to detect viable myocardium, analogous to the data with thallium-201 imaging. Compared with resting Tc-99m sestamibi studies, nitrate-enhanced SPECT has been shown to have a greater ability to predict improvement of regional function after revascularization [43,44], and to provide important prognostic information [45]. The demonstration of "defect reversibility" on nitrate-enhanced compared with resting images may have better accuracy than either technique alone.

All of these studies suggest that by using quantitative measures of regional activity, Tc-99m sestamibi is capable of providing similar data to thallium-201 regarding regional viability and the propensity for improvement in regional wall motion following revascularization. These findings are a reflection of the fact that the magnitude of Tc-99m sestamibi activity within a dysfunctional territory correlates with mitochondrial metabolic activity and the probability of functional recovery. They are consistent with the concept that chronic but reversible regional dysfunction may often exist in the presence of preserved blood flow at rest. Both Tc-99m sestamibi imaging and thallium-201 imaging were recommended (class I indications) for predicting functional recovery in the 2003 guidelines of the American College of Cardiology and the American Heart Association [46]. The image shows examples of the use of Tc-99m sestamibi rest imaging for viability assessment (image 1).

Despite some minor differences in tracer kinetics, a limited amount of data suggests comparable utility of Tc-99m tetrofosmin imaging for viability detection. One report, for example, evaluated a resting injection of Tc-99m tetrofosmin in patients with prior myocardial infarction [23]. Quantitative regional activity of Tc-99m tetrofosmin was significantly higher in those territories supplied by an occluded coronary artery with well-developed collaterals compared with territories supplied by an occluded artery with poor or no collaterals, similar to data reported with Tc-99m sestamibi [24]. Other studies have found that quantitative regional activity of Tc-99m tetrofosmin after rest injection was similar to that of redistribution thallium-201 activity after rest injection in patients with LV dysfunction [19], analogous with equivalently designed comparisons of Tc-99m sestamibi and thallium-201 [25].

The cellular mechanisms responsible for Tc-99m tetrofosmin uptake and retention, particularly in low-flow situations, remain to be determined. As with Tc-99m sestamibi, nitrate enhancement improves the accuracy of Tc-99m tetrofosmin imaging for viability detection [47,48]. When compared with FDG PET, the accuracy of Tc-99m tetrofosmin, especially in the inferior-septal regions of the left ventricle, is improved with attenuation correction [26]. (See "Artifacts in SPECT radionuclide myocardial perfusion imaging", section on 'Attenuation correction'.)

Potential advantages of Tc-99m over thallium-201 include the ability to get better quality gated images, and thus, additive information on regional function, and to apply line source attenuation correction with gadolinium-153 to improve adjudication of inferior attenuation artifacts.

One study of 50 patients with CAD and LV dysfunction addressed the question of whether the addition of functional data to perfusion data improves the accuracy of viability detection. Tc-99m sestamibi ECG-gated SPECT imaging at rest was performed preoperatively and at one and six weeks after revascularization [49]. Perfusion and wall motion data combined had a sensitivity, specificity, positive and negative predictive value, and overall accuracy of 95, 55, 96, 50, and 91 percent, respectively, for identifying myocardial viability. Compared with perfusion data alone, this was an improvement in sensitivity, but at the cost of a lower specificity, and no change in the overall accuracy [49].

Stress imaging versus rest only imaging for viability detection — Most of the data on viability assessment with Tc-99m-labeled agents (where, in contrast to thallium-201 testing, separate injections of tracer are required for stress and rest studies) pertains to the analysis of resting tracer uptake. When the presence or absence of clinically significant amounts of viable myocardium can be determined confidently from the resting study, stress testing is not required for the assessment of myocardial viability. However, when resting tracer uptake is in the "intermediate range," as might occur in regions of non-transmural infarction subtended by a non-critically stenosed coronary artery, the demonstration of inducible ischemia in these regions argues for the presence of viable myocardium. In one study, the finding of reversible ischemia was a more powerful predictor of functional recovery than a fixed defect with a similar degree of resting tracer uptake [50].

POSITRON EMISSION TOMOGRAPHY — Positron emission tomography (PET) is an established noninvasive method of evaluating myocardial perfusion and viability [51]. This technique has the advantage of being able to assess both perfusion and metabolism. PET requires the use of positron-emitting isotopes (such as oxygen-15, carbon-11, nitrogen-13, and fluorine-18), which are cyclotron-produced.

Ischemia shifts myocyte metabolism preferentially to glucose from fatty acids. Thus, uptake of a glucose analog, fluorine-18 labeled deoxyglucose (FDG) by myocytes in an area of dysfunctional myocardium indicates metabolic activity and thus, viability. Regional perfusion can also be assessed with an agent that remains in the vascular space and demonstrates the distribution of blood flow (such as nitrogen n-13 ammonia or rubidium rb-82). As a result, PET imaging has the potential to differentiate between normal, stunned, hibernating, and necrotic myocardium. The presence of enhanced FDG uptake in regions of decreased blood flow (known as a "PET mismatch") defines hibernating myocardium by PET imaging, while a concordant reduction in both metabolism and flow ("PET match") is thought to represent predominantly necrotic myocardium. Regional dysfunction in presence of normal perfusion is indicative of stunning.

Myocardial segments with significant reductions in both blood flow and FDG uptake have only a 20 percent chance of functional improvement following revascularization. In comparison, dysfunctional territories deemed to be hibernating by PET have approximately an 80 to 85 percent chance of functional improvement following revascularization [11,29,52-57].

One study, for example, examined 43 patients with regional asynergy and a mean left ventricular (LV) ejection fraction of 41 percent who were evaluated by PET imaging [57]. The positive and negative predictive values of PET imaging for improvement in asynergy and wall motion score after revascularization were 76 and 96 percent, respectively. Other studies have shown that the extent of myocardium that demonstrates enhanced FDG uptake in patients with ischemic cardiomyopathy may predict the magnitude of improvement in ejection fraction, exercise tolerance, and heart failure symptoms after surgical revascularization [58,59].

Another analysis reported that scar size on FDG PET was an independent predictor of improvement in ejection fraction after revascularization. In 70 patients with a mean resting left ventricular ejection fraction (LVEF) of 26 percent, scars were divided into tertiles graded as small, moderate, or large (0 to 16, 16 to 27.5, and 27.5 to 47 percent of total myocardium, respectively) [60]. The change in EF after revascularization was significantly greater for patients with smaller scars (change of 9.0, 3.7, and 1.3 percent, for small, moderate, or large scars respectively).

Outcome after coronary artery bypass grafting may be improved by incorporating PET derived viability information, in addition to clinical and angiographic data, into the process of selecting patients with impaired LV function for revascularization [61,62]. As an example, one study evaluated the prognostic significance of the presence of viable myocardium, and its interaction with myocardial revascularization, in patients with LV dysfunction after myocardial infarction [62]. Nonfatal ischemic events occurred in 48 percent of medically-treated FDG (+) patients compared with only 8 percent of FDG (+) revascularized patients and 5 percent of patients with FDG (-) myocardium; however, mortality was similar among FDG (+) and FDG (-) patients.

The assessment of viability with metabolic imaging using FDG PET is generally thought to be more sensitive than rest perfusion imaging with SPECT. Clinical experience shows that some myocardial segments that appear severely hypoperfused on SPECT show F-18 FDG uptake, and are thus viable. However, direct comparisons of PET and SPECT in broad groups of patients with a range of LV systolic function are lacking, and therefore, the effect of test choice on patient outcome is unknown. One randomized trial, in which the treating clinicians were blinded to test identity (SPECT or PET), found that the ability to detect myocardial viability with PET or SPECT imaging was the same and that there was no difference in patient outcome when management decisions were based upon the results of either technique [63]. However, patients in this study had only moderate LV dysfunction (LVEF approximately 30 percent), and there are no comparative data in patients with severe LV systolic dysfunction [64].

FDG-SPECT IMAGING — The use of specialized collimators has allowed the adaptation of widely available SPECT imaging cameras to capture the 511 keV positrons emanating from fluorine-18 FDG [65-67]. Preliminary data from some studies of patients revascularized for coronary heart disease-related left ventricular (LV) dysfunction have demonstrated superior predictive values for functional recovery with FDG-SPECT compared with other techniques, particularly thallium-201 SPECT with reinjection and low dose dobutamine echocardiography [13,53,68].

As an example, one study of patients with LV dysfunction reported that significant improvement of global LV function occurred in those with three or more viable segments on FDG-SPECT [68]. Another study found that the combined use of both FDG-SPECT and dobutamine echocardiography derived data resulted in the most accurate prediction of functional recovery in hypokinetic segments [13]. On the other hand, one study comparing FDG-SPECT with PET and thallium-201 [69] SPECT did report that although FDG-SPECT significantly increased the sensitivity for detecting viable myocardium, 27 percent of segments were falsely identified as viable when judged nonviable by both PET and thallium-201 [70].

Therefore, the relative merits of FDG-SPECT and the more conventional techniques for viability assessment need to be assessed in further clinical trials. Analogous to PET, obtaining simultaneous perfusion data during FDG-SPECT imaging may improve accuracy for viability detection [71,72]. Future studies will determine whether the physical problems associated with gamma camera imaging of this agent, as well as technical issues such as the need for attenuation correction, can be overcome to a degree that this technique can provide superior information, rather than just similar information, to conventional (and less expensive) SPECT approaches.

COMPARISON WITH NON-NUCLEAR TECHNIQUES — Dobutamine echocardiography is an established technique for viability detection. Newer techniques such as cardiovascular magnetic resonance (CMR) and myocardial contrast echocardiography (MCE) have also been tested in clinical trials. (See "Dobutamine stress echocardiography in the evaluation of hibernating myocardium" and "Evaluation of hibernating myocardium".)

The relative predictive value of the different forms of radionuclide myocardial perfusion imaging and of dobutamine echocardiography for detecting hibernating myocardium was evaluated in an analysis from 52 published studies that utilized thallium stress-redistribution-reinjection SPECT, thallium rest-redistribution SPECT, FDG-PET scanning, technetium-sestamibi SPECT, or low dose dobutamine echocardiography [73,74]. The following findings were noted:

●For each technique, the negative predictive value was higher than the positive predictive value. The highest negative predictive values were seen with FDG-PET, reinjection thallium SPECT, and dobutamine echocardiography, while lower values were noted for rest-redistribution thallium SPECT and technetium-sestamibi SPECT.

●The highest positive predictive value was seen with dobutamine echocardiography, with intermediate values for FDG-PET, rest-redistribution thallium SPECT, and technetium-sestamibi SPECT, and the lowest value for reinjection thallium SPECT.

Most of these studies did not compare imaging techniques in the same patients. In a subset of studies in which two techniques were compared to detect viability, the pooled results showed that dobutamine echocardiography had a significantly higher positive predictive value than nuclear imaging (84 versus 75 percent) and a significantly lower negative predictive value (69 versus 80 percent). It is important to note that differences in sensitivity and/or specificity to detect viability on a segmental basis may not translate directly into better information for decision-making for patients. In an individual patient, a difference in one or two segments is not that likely to drive decisions in different directions. For example, though it is reasonably well established that PET detection of viability (by segments) is stronger than that done by SPECT imaging, in the aforementioned randomized trial, comparing decisions and outcomes driven by information from SPECT or PET imaging of viability on a patient basis [63], there were no differences identified

CMR enhanced with gadolinium is being increasingly used for viability assessment. Lack of enhancement is a sensitive marker of the absence of scar tissue and is taken to imply the presence of viability. Comparison to prior data from thallium-201 studies suggests a similar lack of discriminatory power for predicting functional recovery in segments with intermediate amounts of residual viability. Recent studies suggest that some segments of severely dysfunctional myocardium which are deemed non-viable with conventional techniques may show functional recovery after revascularization if there is no enhancement on CMR. Thus, contrast-enhanced CMR may be more sensitive for the prediction of function recovery in the most severely dysfunctional myocardial segments [75]. To some degree, this may reflect the better resolution of the CMR technique compared with SPECT for instance, which would be advantageous in the setting of a very dilated left ventricle (LV) with relatively thin walls.

ROLE OF VIABILITY ASSESSMENT — The role of viability testing in patients with reduced systolic function and coronary artery disease is discussed separately. (See "Treatment of ischemic cardiomyopathy", section on 'Additional imaging' and "Treatment of ischemic cardiomyopathy", section on 'General principles'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in adults" and "Society guideline links: Chronic coronary syndrome" and "Society guideline links: Multimodality cardiovascular imaging appropriate use criteria".)

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SUMMARY AND RECOMMENDATIONS

●Role of viability testing – The role of viability testing in patients with reduced systolic function and coronary artery disease is discussed separately. (See "Treatment of ischemic cardiomyopathy", section on 'Additional imaging' and "Treatment of ischemic cardiomyopathy", section on 'General principles'.)

●Choice of imaging technique – The choice of imaging technique is individualized to the patient and based on center experience. Each of the available imaging modalities has similar diagnostic accuracy for ruling in or ruling out the presence of viability (figure 2). (See 'Comparison with non-nuclear techniques' above.)

●Choice of nuclear tracer – Thallium-201, Tc-99m sestamibi, Tc-99m tetrofosmin, and fluorine-18 labeled deoxyglucose positron emission tomography (FDG PET) are capable of providing high-quality information on myocardial viability. Centers should use the tracer with which they have the greatest experience.

●Approach to viability assessment with nuclear imaging – The approach to viability testing with nuclear imaging depends on whether there is a suspicion of ischemia (see 'Stress imaging versus rest only imaging for viability detection' above):

•Evaluation for viability only – In patients in whom the presence of viability would alter management and there is no suspicion of ischemia, we typically perform a resting perfusion scan first. The use of sublingual nitrate prior to tracer injection is variable. The findings from rest imaging include:

-Viability present at rest – If the resting study clearly establishes the presence of viability (eg, perfusion is intact), subsequent stress testing or redistribution images are generally not required for the assessment of viability.

-Indeterminate or no viability at rest – In cases where the resting study shows "indeterminate" perfusion or if perfusion is severely decreased or absent, additional imaging is required to identify whether viability is present. In such cases, we typically perform redistribution imaging.

•Evaluation for ischemia and viability – If ischemia is suspected and viability is of clinical interest, a stress protocol should be performed to identify ischemia and to potentially identify viability:

-Viability detected during stress imaging – If viability is identified during stress imaging, the patient typically does not require further imaging.

-No evidence of viability during stress testing – If stress imaging redemonstrates areas of decreased perfusion, redistribution imaging is required to evaluate for ischemia.