Another echocardiographic technique used in viability imaging is myocardial contrast echocardiography (MCE) , which uses gas-filled microbubbles to evaluate the integrity of the microvasculature [7]. The basic protocol involves continuous intravenous infusion of microbubbles until a steady state is achieved and measurement of the rate of reemergence (myocardial blood flow velocity) and the concentration in tissue (myocardial blood volume fraction) following destruction with a high-power ultrasound pulse [8, 9]. Although widespread clinical use has been limited, MCE has been used to determine the extent of viable myocardial tissue and predict functional recovery after revascularization in acute coronary syndromes [10–12], as well as in chronic ischemic cardiomyopathy [13]. ◘ Figure 14.2 shows examples of myocardial contrast echocardiography in patients with viable (Panel a) and nonviable (Panel b) apical segments. An apical thrombus is also noted in the patient with an acute myocardial infarction (MI) depicted on Panel b.

Strain, regional deformation, and strain rate (the rate of regional deformation)—either measured by tissue Doppler imaging or speckle tracking—are rapidly becoming indispensable echocardiographic tools for assessing regional left ventricular systolic function in various disease processes. Strain imaging has the potential to help avoid the common pitfalls inherent in DSE, such as the subjective nature of regional wall motion assessment and the challenge of discriminating between a segment that’s actively contracting from one that’s “tethered” [14, 15]. The use of strain imaging has identified multiple variables that favor myocardial viability and functional recovery. These include increase in peak systolic strain rate by more than 0.23/s [16], high-end-systolic strain [17], and a >9.5 % change in radial strain [18]. Limited data pertaining to the application of strain imaging for assessing myocardial viability exist, and further studies are warranted to clarify its clinical utility. ◘ Figure 14.3 shows an example of strain rate tracings at rest (solid line) and during dobutamine infusion (dotted line) for one cardiac cycle of a hypokinetic segment at rest, shown to be viable by 18-fluorodeoxyglucose (FDG) PET imaging. The peak systolic strain rate increased from 1.1 s⁻¹ at rest to 2.0 s⁻¹ during dobutamine stimulation .

Myocardial wall thinning occurs in areas of transmural myocardial infarction and is commonly considered a surrogate marker for the presence of nonviable tissue [19, 20]. The left ventricular end-diastolic wall thickness (EDWT) is easy to determine using two-dimensional (2D) echocardiography. In small, prospective studies involving patients with coronary artery disease and left ventricular dysfunction, EDWT > 6 mm was shown to have high sensitivity but low specificity to identify viable myocardium and predict functional recovery. The sensitivity of EDWT as an index of viability was improved by the addition of contractile reserve with dobutamine stress echocardiography [21, 22]. Similar findings were obtained when cardiac magnetic resonance imaging was used to measure EDWT using cutoff values greater than 5.5–6 mm [23]. However, a recent landmark cardiac magnetic resonance (CMR) imaging study showed that, among patients with coronary artery disease and regional wall thinning, limited scar burden was present in 18 % and was associated with improved contractility and resolution of wall thinning after revascularization [24]. Thus, myocardial thinning is potentially reversible and, therefore, should not be considered a permanent state. Similarly, EDWT is not a reliable predictor of viability .

Single-photon emission computed tomography (SPECT) uses radiotracers to assess perfusion and cell membrane/mitochondrial integrity as hallmarks of viability. The two radiotracers used most commonly with SPECT are thallium 201 (TI) and technetium 99m (Tc) [1]. TI is a potassium analog that is actively transported into myocytes by a Na/K ATPase-dependent mechanism, thus requiring an intact cell membrane. As TI kinetics are directly proportional to tissue blood flow, normal tissue has more rapid uptake and washout than underperfused, viable tissue. Myocardial TI is then exchanged continuously with the reservoir of systemic blood pool TI, with net efflux from the myocardium. Images obtained early after tracer injection reflect blood flow, whereas retention and redistribution of thallium over a 4–24-h period reflect intact cell membrane function and, thus, myocyte viability. TI redistribution in regions that initially had a perfusion defect is the hallmark of viability when using SPECT .

Numerous viability protocols have been described, which underscores the lack of standard criteria. Common protocols include stress redistribution, which provides information for both inducible ischemia and cellular viability and rest redistribution, which provides information on myocardial blood flow at rest and cellular viability. Whereas rest redistribution needs only one injection of TI, stress redistribution needs a reinjection of a small dose at rest, as the initial uptake of TI during stress may be severely reduced in some patients with significant CAD. The second injection during stress redistribution imaging can be done early (3–4 h) or late (8–72 h) following the initial injection.

Tc-labeled radiotracers (sestamibi and tetrofosmin) are widely used for performing stress myocardial perfusion imaging. Although accumulation and retention of Tc is a passive process driven by transmembrane electrochemical gradient, it still depends on mitochondrial membrane integrity. The usual stress protocols require modification (such as administration of nitrates) to optimize the radiotracer delivery to hibernating myocardium, particularly in patients with very severe left ventricular dysfunction. In general, TI is the radiotracer of choice with SPECT to assess viability [25].

Thallium protocols yield good positive and negative predictive values (70–90 % range) for recovery of function after revascularization. However, a pooled analysis of TI viability studies showed high sensitivity (88 %) but low specificity (49 %), suggesting overestimation of recovery by TI. SPECT has limited ability to differentiate between subendocardial and transmural scars, primarily due to low spatial resolution. ◘ Figure 14.4 shows an example of a Tl viability study. The top panel shows Tl images at stress, redistribution, and reinjection. The bottom panel shows corresponding gross pathology and histopathology of a mid-ventricular left ventricular (LV) slice. On the thallium study, extensive perfusion defects are visible in the anterior, septal, and inferolateral regions during stress. On redistribution, partial reversibility of the anterior region is seen, as well as complete reversibility of the septum and an irreversible defect in the inferolateral region. After thallium reinjection, complete reversibility of the septal and anterior regions is noted with a persistent irreversible defect in the inferolateral region. This is consistent with viability in the septal and anterior regions and infarct in the inferolateral region. On gross pathology, white fibrotic myocardium is visible in the inferolateral region, and histomorphologic analysis shows a significant amount of red-stained collagen intermixed within normal-looking myocytes in the same area .

Positron emission tomography (PET) uses separate positron-emitting radiotracers to assess perfusion and metabolism, based on the concept that metabolism is preserved relative to flow in hypoperfused but viable myocardium. Perfusion is assessed with N-13 ammonia, which needs an on-site cyclotron, or rubidium-82, which is produced by a generator. Metabolism is measured by uptake of 18-FDG, which is a glucose analog. It is transported into the cell and effectively fixed in the myocardium through phosphorylation by hexokinase [25].

Under normal fasting conditions, the myocardium mainly uses free fatty acids as the primary energy source. After a meal or glucose load, the combined effects of insulin and the increased glucose concentration result in viable myocardium preferentially switching to glucose as the preferred energy substrate. Importantly, myocardial ischemia may further increase the overall proportion of glucose utilization in the myocardium. FDG uptake into the myocardium is dependent on the insulin-sensitive glucose transporters that can be activated by either oral glucose loading or administration of insulin before tracer administration. This is the exact opposite of protocols used in oncology or for detection of cardiac sarcoidosis, where imaging is done in a fasting state to minimize FDG uptake by normal tissue.

Normal myocardium is characterized by normal flow, normal glucose uptake (matched perfusion/metabolism); infarcted, nonviable myocardium has both decreased flow and glucose uptake (matched perfusion/metabolism defect); hibernating but viable myocardium has reduced resting flow with normal or increased glucose uptake (mismatched perfusion/metabolism). Using this concept, myocardial segments assessed with PET show (1) normal flow/metabolism (viable), (2) mild-matched reduction in flow/metabolism (subendocardial scar), (3) severe-matched defect (transmural scar), or (4) mismatch with resting perfusion defect and preserved glucose uptake (hibernating but viable). Viability is denoted by greater than 50 % FDG uptake in a myocardial segment.

The accuracy of PET to predict functional recovery after revascularization is high, with positive and negative predictive values in the 80–90 % range. Importantly, this accuracy holds even in patients with severe left ventricular dysfunction. From a pooled analysis of studies investigating the value of preserved FDG uptake in predicting functional recovery, sensitivity was 88 % and specificity was 73 %. The extent of viability shown on PET needed to predict improvement in mortality after revascularization varies in different studies between 7 and 20 %. This reflects the fact that viability is not a binary figure but rather a continuum, where increasing hibernation implies both increased risk and increased potential for recovery. Benefits of PET imaging are superior spatial and temporal resolution, improved attenuation and scatter correction compared to SPECT, and the ability to image patients with severe renal disease and pacemakers/defibrillators who cannot have CMR imaging. Limitations of PET include limited availability, requirement of an on-site cyclotron for N-13 ammonia, the need to create a tightly controlled metabolic milieu, and suboptimal performance in diabetics due to reduced myocardial extraction of 18-FDG [25]. ◘ Figure 14.5 shows mid-ventricular short-axis images of resting blood flow (top panel) and 18-FDG uptake on PET (bottom panel) in a patient with LV dysfunction due to a recent MI in the left anterior descending territory treated initially with thrombolysis. Extensive reduction in resting blood flow in the anterior wall is seen with enhanced 18-FDG uptake (flow/metabolism mismatch pattern). This patient had improved LV function following surgical revascularization.

Viability imaging with cardiac computed tomography (CCT ) uses a premise similar to that for delayed-enhancement CMR with gadolinium, as iodine is also primarily an extracellular, interstitial agent with similar contrast kinetics [26]. Areas of myocardial damage provide an increased volume of distribution for contrast, thus showing contrast enhancement on repeat imaging about 10 min after contrast delivery. The typical CCT protocol includes two scans. The first scan is a routine coronary angiogram that visualizes the coronary arteries and myocardial first-pass perfusion. Hypoperfused myocardium due to coronary stenosis or infarction appears hypoenhanced due to slow contrast wash-in. The second scan, obtained about 10 min later (with no additional contrast injection), is performed to assess myocardial viability. Scar tissue will appear as hyperenhanced compared with surrounding viable myocardium. A major disadvantage of CCT for delayed-enhancement imaging is its low contrast-to-noise ratio, with poor contrast difference between normal and infarcted myocardium [26]. Currently, CCT perfusion is not used widely to assess viability. ◘ Figure 14.6 shows images from viability studies by CCT compared to delayed-enhancement magnetic resonance imaging (DE-CMR) in the same patients.

Cardiac magnetic resonance imaging provides information on viability by a technique called delayed enhancement cardiac magnetic resonance (DE-CMR ). Using this technique, irreversibly injured myocardium is visualized as bright (hyperenhanced) regions. Hyperenhancement on delayed-enhancement images represents necrosis in the acute or scar tissue in the chronic myocardial infarction settings. Viable myocardium, either normal or reversibly injured, appears dark. Gadolinium-based contrast is injected intravenously at a dose of 0.075–0.20 mmol/kg body weight. If a stress and rest perfusion scan precede the viability scan, no additional contrast media injection may be necessary. ◘ Figure 14.7 shows typical cine and DE-CMR images.

Contrast agents currently used for the DE-CMR technique are gadolinium chelates. They are extracellular or interstitial agents as they leave the vascular bed and enter the extracellular or interstitial space, but not the intracellular space. In healthy, viable myocardium, the distribution volume (i.e., the volume available for contrast agent distribution) is small, because the intracellular space from healthy myocardial cells occupies a large portion of the tissue volume (about 75–80 % of the water space) and is unavailable to the contrast agent. In acute infarction, the ruptured cardiomyocyte membranes enable the gadolinium contrast agent to passively diffuse into the formerly intact intracellular space, resulting in an increased contrast agent concentration and “hyperenhancement.” In chronic infarction, the myocardial tissue consists of dense scar with an increased extracellular or interstitial space between collagen fibers and, therefore, an increased distribution volume for the contrast agent relative to normal myocardium. Thus, a direct inverse relationship exists between the gadolinium contrast concentration within the myocardium and the percentage of viable myocytes (◘ Fig. 14.8) [27].