Diagnostic and Prognostic Value of Cardiac Magnetic Resonance Imaging in Assessing Myocardial Viability

Abstract

Assessment of viability is pivotal to the prognosis of patients with chronic coronary artery disease (CAD) and left ventricular dysfunction. Patients with viable myocardium have a better prognosis with revascularization; however, patients with nonviable myocardium have worse outcomes with higher perioperative morbidity and mortality subsequent to revascularization. Cardiac magnetic resonance (CMR) imaging not only is the current reference standard technique in measuring cardiac chamber size and function and myocardial mass and volume but also provides spatially registered 2- or 3-dimensional data sets in myocardial perfusion and myocardial contrast enhancement in the same imaging session. Late gadolinium enhancement by CMR is the best current technique in discriminating myocardial scar versus viable myocardium. An extensive body of preclinical evidence has validated the detection and characterization of the morphology of infarcted tissue. In clinical studies, infarct characteristics by CMR has demonstrated a strong clinical utility in the prediction of left ventricular functional recovery and patient prognosis. In this paper, we aim to review the current CMR techniques in characterizing the spectrum of myocardial changes because of CAD, in the prediction of myocardial viability, and the current evidence of CMR's role in patient prognosis. In addition, we will also review the current literature comparing the clinical utility of CMR with other established imaging modalities in the assessment of CAD.

CLINICAL DEFINITION OF DYSFUNCTIONAL BUT VIABLE MYOCARDIUM

Impaired resting left ventricular (LV) systolic function was thought to be an irreversible process until the introduction of the concepts of stunned and hibernating myocardium.¹²In patients with coronary artery disease (CAD), the dysfunctional myocardium that has been exposed to acute or chronic ischemic changes may remain viable and, depending on the severity and duration of ischemia, may be reversed with revascularization.¹³

Myocardial Stunning

An ischemic insult not of sufficient severity or duration to produce myocardial necrosis, but which interferes with normal myocardial function, biochemical processes, and ultrastructure, despite restoration of epicardial coronary blood flow, can be described as myocardial stunning.¹⁴ The severity and duration of these postischemic changes depend on the length and intensity of the ischemia and on the conditions of the myocardium before the ischemic episode. Stunned myocardium has abnormal wall motion that tends to normalize in response to inotropes and postextrasystolic potentiation.¹⁵ Once the epicardial coronary blood flow is restored and no myocardial necrosis has taken place, myocardial perfusion returns and metabolism becomes adequate. Stunned myocardium returns to normal after a prolonged period (hours to weeks).¹⁶

Hibernating Myocardium

The hibernating myocardium refers to resting LV dysfunction due to reduced coronary blood flow that can be at least partially reversed by myocardial revascularization and/or by reducing myocardial oxygen demand.¹² Diagnosis of hibernating myocardium is important because patients can benefit from coronary mechanical revascularization as soon as possible.¹³ Hibernating myocardium is not completely adapted to chronic underperfusion: cellular degeneration and myocyte loss accompanied by reparative fibrosis occur and the structural integrity of the myocardium deteriorates.¹⁷ Hibernating myocardium without excessive degeneration of cellular elements can demonstrate improvement of contractile function after nitrates, inotropes, postextrasystolic potentiation, or successful restoration of coronary blood flow.

LEFT VENTRICULAR REMODELING

Left ventricular remodeling can be described as maladaptive alterations in ventricular geometry and function in response to myocardial injury. Remodeling is characterized by a complex series of histopathologic changes in both injured and uninjured segments after an ischemic insult.

Animal studies have shown that early structural changes after acute myocardial infarction (MI) include LV tissue loss with concomitant with LV cavity dilation and later changes consist of contraction of infarcted tissue with compensatory hypertrophy of noninfarcted tissue.¹⁸ This remodeling can affect the LV systolic function and the patients' prognosis for survival. After an acute myocardial infarct, the noninfarcted region also undergoes changes consistent with a secondary volume-overload hypertrophy that can be progressive. The extent of ventricular enlargement after infarction is related to the magnitude of the initial damage to the myocardium, and although an increase in cavity size tends to restore stroke volume despite a persistently depressed ejection fraction, ventricular dilation has a strong adverse impact on patient survival.¹⁹ With its high-spatial resolution, contrast-to-noise ratio, and multimodality capability, cardiac magnetic resonance (CMR) has played a key role in understanding the natural history of LV remodeling and the role of pharmacological and nonpharmacological interventions in attenuating the process of remodeling.

DETECTION OF VIABILITY BY CMR

Cine Imaging: Assessment of LV Systolic Global and Regional Function

With high reproducibility and accuracy, CMR is currently the noninvasive reference standard for measuring LV ejection fraction (LVEF) and ventricular volumes.^20,21 Typically, bright blood gradient echo sequences are obtained covering the entire left ventricle with short-axis views from the mitral plane at slice thickness of approximately 10 mm, during a 10- to 15-second breath-hold. The spatial and temporal resolution of cine magnetic resonance imaging (MRI) allows accurate quantitation of myocardial wall thickness and regional dysfunction. Baer et al^22,23 studied 43 patients with chronic infarction and mild LV dysfunction (mean [SD] LVEF, 42% [10]) with dobutamine cine CMR before and 4 to 6 months after successful revascularization. An end-diastolic wall thickness of 5.5 mm or greater (based on a −2.5 SD from normal individuals) had a 92% sensitivity but at a limited 56% specificity for predicting recovery of segmental function after successful epicardial revascularization. This finding is not surprising because myocardial wall thickness may include subendocardial infarcted tissue and a thinned epicardial rim of viable myocardium, which may not be sufficient to regain regional systolic thickening despite successful coronary revascularization.^24,25 Myocardial thickness has limited independent utility in predicting future segmental recovery also during the acute or subacute phase of MI when local infarct remodeling is incomplete (up to 6 months postacute infarction). In this setting, local edema and cellular infiltrates may increase regional wall thickness. Augmentation of regional contractility (ie, improvement of wall thickening on an inotropic challenge) in response to inotropic stimulus such as low-dose (5-10 μg/kg per minute) dobutamine challenge has been well validated in identifying segmental viability from both the vast body of evidence from echocardiography or cine CMR.^23,26,27 Demonstration of segmental contractile reserve by cine CMR is a safe and reliable method in predicting recovery from CAD by either qualitative or quantitative methods. The role of low-dose dobutamine stress echocardiography (DSE) in assessing inotropic reserve in the detection of viable myocardium is well established.²⁸ Low-dose dobutamine-MRI (Dob-MRI) has emerged as a technique of comparable accuracy using the same principle.^23,26 In the study of Baer et al,²² comparing low-dose dobutamine transesophageal echocardiography and low-dose Dob-MRI studies in 103 patients after MI, the positive and negative predictive accuracies of dobutamine transesophageal echocardiography and Dob-MRI for the prediction of LV functional recovery after revascularization were similar (85% vs 92% and 80% vs 85%, both were not significant). The same group evaluated viability by MRI after MI comparing to fluorine-18 fluorodeoxy glucose-positron emission tomography (¹⁸F FDG-PET) as the "criterion standard." Dobutamine-MRI demonstrated a sensitivity of 88% and specificity of 87%. Baer et al²⁹ also assessed the utility of a combined criterion of wall thickness and contractile reserve using cine CMR at rest and at low-dose dobutamine challenge in the prediction of contractile recovery of any infarcted segments. Myocardial viability in an infarcted region was defined by a diastolic wall thickness of 5.5 mm or greater and the presence of systolic wall thickening of 2 mm or greater in at least 50% of the dysfunctional segments of the infarcted region. On the basis of their study, although resting wall thickness of 5.5 mm or greater showed a high sensitivity for identifying viable myocardial segments (92%), it showed a low specificity of 56%. However, a physiological contractile reserve, as demonstrated by a systolic wall thickening of 2 mm or greater, demonstrated an improved specificity and a preserved sensitivity in the prediction of segmental contractile recovery after revascularization (sensitivity, 89%; specificity, 94%). Other similar studies consistently reported high specificity using contractile reserve by dobutamine CMR in identifying viable myocardial segments.^26,27 Geskin et al³⁰ assessed the utility of low-dose dobutamine cine CMR in predicting myocardial viability in the early period after acute MI. In their study, quantitative analysis of segmental myocardial function was made possible with the use of magnetic resonance high-resolution tagging techniques, which allowed quantitation of the intramyocardial circumferential shortening and minimized the effect of through-plane motion on segmental contraction during low-dose dobutamine challenge. Their study concluded that, early after acute MI, dysfunctional but viable myocardial segments can be identified by anexaggerated circumferential shortening in the subepicardial and midmyocardial layers compared to those of normal segments. One potential limitation exists in using only dobutamine cine contractile reserve in detecting segmental viability. Although excellent specificity for predicting segmental contractile recovery has been consistently reported, the sensitivity of low-dose dobutamine contractile reserve imaging has only been in the moderate range (50-76%) in segments with resting akinesia or dyskinesia.³¹ This is attributed to the fact that in the presence of severe coronary stenosis and hypoperfusion, viable myocardial segments may fail to demonstrate contractile reserve with low-dose dobutamine because of rapid development of ischemia.³²

First-Pass Myocardial Perfusion CMR Imaging

Whereas nuclear techniques have been the main clinical tools in assessing myocardial perfusion in the past decades, CMR perfusion has several important technical advantages in assessing patients with symptoms of CAD. First-pass CMR perfusion imaging is based on fast T1-weighted image collected during rapid injection of an intravenously administered contrast bolus, which results in the enhancement of the perfused myocardium. Apart from imaging techniques, there are fundamental differences in contrast kinetics, which merit the readers' attention in understanding the differences between these 2 techniques. With myocardial tracers used in single-photon emission computed tomography (SPECT), areas with decreased myocardial perfusion and areas with a reduced number of viable cells result in reduced tracer uptake.^33,34 In contrast, gadolinium-based MRI contrast agents are not dependent on myocyte uptake. Consequently, whereas reperfused but infarcted myocardium demonstrate an absence of regional tracer uptake on SPECT images, the extracellular gadolinium kinetics during first-pass injection reflect primarily coronary blood flow integrity, thus the same myocardial region consisted of well-perfused infarcted tissue may appear without defect on first-pass CMR perfusion.³⁵ This provides unique advantages of CMR perfusion over the current nuclear techniques in assessing myocardial blood flow after MI in assessing the following clinical settings: (1) evaluating the patency of implanted coronary stents in patients presented with recurrent symptoms after MI and (2) determining the size and severity of the no-reflow zone within infarction.³⁶ Given the noninvasive nature of CMR without the use of ionizing radiation, serial assessment of these situations becomes possible and practical. Others have used the quantitative nature of CMR perfusion imaging to investigate hibernating myocardium. Selvanayagam et al³⁷ assessed the issue of blood flow reduction in hibernating myocardium using high-resolution quantitative CMR in 27 patients with 1-or 2-vessel coronary disease undergoing percutaneous coronary intervention and showed that resting myocardial blood flow is markedly reduced in dysfunctional myocardial segments supplied by severely stenosed coronary arteries.

Late Gadolinium Enhancement CMR Imaging

Gadolinium-diethylenetriamine pentaacetic acid is primarily an extracellular, interstitial agent; therefore, the volume of distribution for the contrast molecules increases within the infarcted imaging voxel.^38-40 The increased gadolinium concentration within the infarcted tissue shortens the T1 relaxation time. Hence, infarcts appear hyper enhanced, compared to the neighboring noninfarcted tissue, on reaching a transient steady state of wash-in and washout of the interstitium. The extracellular space is increased in collagenous scars, and it explains the increased volume of distribution for gadolinium in chronic infarction. Reduced capillary density in chronic scars also reduces contrast washout, leading to the hyper enhancement. Late gadolinium enhancement (LGE) by CMR has been reported in early studies more than 20 years ago (Fig. 1).^41-43 In 2001, Simonetti et al⁴⁵ developed a new pulse sequence technique that formed the basis of current imaging of LGE across the different MRI vendors (Fig. 2). Using an inversion-recovery prepulse and a segmented fast gradient echo data acquisition, the contrast-to-noise ratio of infarcted and normal myocardium was improved by more than 10-fold compared to older techniques. Any protocol for assessing LGE using an inversion-recovery MRI pulse sequence must properly adjust the inversion time (T_I). By adjusting the T_I to null signal from normal myocardial regions, the difference in image intensity between the infarcted and the normal myocardium is maximized.

FIGURE 1: Spatial resolution by the current LGE CMR techniques is in the order of 5- to 7-fold higher than SPECT imaging. This figure illustrates the detection of subendocardial infarction commonly detected by LGE CMR. Adapted from Wagner et al.⁴⁴

FIGURE 2: T1-weighted inversion recovery technique using a gradient echo readout for imaging of LGE. By setting an appropriate trigger delay interval according to the patient's heart rate, in the early part of the cardiac cycle, image acquisition can be performed in middiastole to minimize motion blurring. By setting a proper time delay (T _I) after the 180-degree inversion pulse has been placed, maximal contrast between the unenhanced normal myocardium and the enhanced LGE can be detected. These parameters are crucial in obtaining the high image quality of LGE illustrated on the figure on the right. (Part of this figure is adapted from Simonetti et al.⁴⁴)

Hillenbrand et al⁴⁶ tested the hypothesis that contrast-enhanced MRI can index myocardial salvage by observing the transmural extent of hyperenhancement early after injury. In this study, the left anterior descending coronary artery was occluded in dogs for either 45 minutes, 90 minutes, or permanently. Cine and contrast-enhanced MRI were performed 3 days after the procedure; cine MRI was also done 10 and 28 days after the procedure. The mean transmural extent of hyperenhancement for the 45-minute occlusion group was 22% of the 90-minute group and 18% of the permanent occlusion group (P < 0.05 for both). The transmural extent of hyperenhancement on day 3 was related to future improvement in both wall thickening score and absolute wall thickening at 10 and 28 days (P = 0.0001 for each). They demonstrated that the transmural extent of hyperenhancement by contrast-enhanced MRI is inversely related to the early restoration of flow and future improvement in contractile function. Recent studies using this technique had validated the relationship between hyperenhanced myocardium at contrast-enhanced MRI and myocardial necrosis determined by histologic diagnosis.^40,47-49 Kim et al^45-50 showed that delayed enhancement technique delineates the transmural extent of infarction and distinguishes between reversible and irreversible myocardial injury regardless of the extent of wall motion at rest, the age of the infarct, or the reperfusion status. In their landmark study, the size and shape of hyperenhanced areas of LGE were demonstrated to be almost identical to areas of irreversible injury defined bytetrazolium staining. They further demonstrated that there exists close correlation between infarct size by CMR and histopathology on day 1, day 3, and week 8 after infarction, whereas stunned myocardium induced by brief coronary occlusion of a non-infarct-related coronary artery did not exhibit LGE. Ischemic but viable myocardium also did not enhance with gadolinium. Reversible myocardial dysfunction can therefore be identified by LGE imaging before coronary revascularization and can be used to predict whether regions of abnormal ventricular contraction will improve after revascularization in patients with CAD. In a clinical study by Kim et al,⁶ LGE imaging was performed in 50 patients with LV dysfunction before surgical or percutaneous revascularization. Hyperenhancement of myocardial tissue was observed in 40 of 50 patients before revascularization. As the transmural extent (in tertiles) of LGE before revascularization increased, the degree of improvement in regional contractility after revascularization decreased in a stepwise fashion. The likelihood of functional improvement in regions without any LGE was 86% for segments with hypokinesis and 100% for segments with akinesis ordyskinesis. Some of the regions with LGE would have been considered nonviable according to the wall motion-improvement criteria, although a sizable epicardial rim of viable tissue is present. The authors concluded that the detection of an epicardial rim of viable tissue by LGE imaging represents diagnostic information that is not available with the use of other noninvasive imaging techniques. Previous data revealed marked changes ingadolinium-diethylenetriamine pentaacetic acid wash-in and washout kinetics within the infarct zone compared with normal myocardium. Kim et al⁵⁰ suggested a different approach to identifyviable myocardium:that contrast MRI in combination with cine MRI can be used in the acute setting to distinguish between acute MI (LGE with contractile dysfunction), injured but viable myocardium (no LGE but with contractile dysfunction), and normal myocardium (no LGE and with normal function).

For the past years, more advanced approaches have further improved the applicability of LGE techniques by CMR. Kellman et al⁵¹ developed an algorithm in improving LGE image quality using phase-sensitive reconstruction and surface coil intensity correction. This approach reduces senitivity to nonprecise selection of T_I, which deteriorates image quality. Quantitation of the myocardial extent of LGE provides reader independent assessment of infarct sizing, which is currently most precisely measured by CMR. More recently, Hsu et al⁵² demonstrated that an algorithm combining automated feature analysis and threshold detection yielded the highest accuracy in infarct sizing. The increasing availability of 3-T MRI that provides a significant improvement of tissue contrast in T1-weighted imaging techniques relying on Gd-based contrast enhancement is likely to result in increased utilization of this technique.⁵³ Our group had found that both visual detection of the presence of LGE and computer-assisted quantitation of LGE extent substantially improved the clinical prognostication of adverse cardiac events in patients with new symptoms of CAD but without a history of MI, beyond common markers such as LVEF. Others have used the high-spatial resolution and contrast-to-noise ratio of LGE imaging to further evaluate the physiologic basis of tissue heterogeneity of LGE. Using semiautomated signal intensity thresholding criteria on LGE images, Schmidt et al⁵⁴ assessed 47 patients with clinical indications for automated internal cardioverter defibrillator and found a significant association of inducible sustained monomorphic ventricular tachycardia during electrophysiological testing and tissue heterogeneity. This finding supports the notion that CMR can detect a peri-infarct zone with intermediate signal intensity, which corresponds to increased potentials for ventricular arrhythmogenicity. There has been growing clinical evidence that tissue characteristics of LGE provide information valuable to patient outcome. Two separate clinical reports demonstrate the unique and important prognostic value of microvascular obstruction identified on LGE imaging in patients who experienced a recent MI.^8,9 More recently, in a clinical cohort¹¹ of 144 post-MI patients observed for up to 4.5 years, our group found that assessment of infarct heterogeneity, using an algorithm similar to that Schmidt et al,⁵⁴ to be the strongest predictor of post-MI mortality, complementary to the robust prognostic value of LV end-systolic volume. There is currently one multicenter trial investigating the role of CMR in guiding medical management or placement of automated internal cardioverter defibrillator in patients who experienced MI.

Viability by Cellular Metabolism by Magnetic Resonance Spectroscopy

Magnetic resonance spectroscopy (MRS) is the only current technique that has the unique ability to measure the presence of subcellular components required for maintained cellular integrity. To achieve this, MRS techniques samples the density of protons located on molecules other than water, such as creatine or phosphate. Energy resource essential for myocardial contractility and relaxation is produced and stored in the mitochondria in the form of adenosine triphosphate (ATP). Under the catalytic action of creatine kinase, phosphocreatine acts as a free-energy carrier between sites of free energy production with sites of consumption (eg, myofibrils or ion transport channels at the cell membrane) through diffusion. Therefore, by quantifying the concentrations and ratios of phosphocreatine and ATP in a small volume of myocardium, phosphorus-31 (³¹P) spectroscopy can assess myocardial energy metabolism and thus determine the integrity of myocardial cellular functions. Yabe et al⁵⁵ demonstrated that MRS could differentiate myocardial viability inpatients who experienced an acute MI by comparing against evidence of viability by thallium redistribution. Weiss et al⁵⁶ demonstrated that the transient decrease in the phosphocreatine to ATP ratio was related to myocardial ischemia induced by handgrip exercise. Creatine kinase reaction in the myocardium serves as the heart's main energy reserve. Proton (¹H) MRS has up to 20-fold improved sensitivity than ³¹P MRS and can quantify both phosphorylated and unphosphorylated creatine in the myocardium from any part of the left ventricle. Bottomley and Weiss⁵⁷ developed and validated the technique using ¹H MRS against animal models of MI and found that assessing regional depletion of myocardial creatine provides a metabolic method to distinguish healthy from infarcted nonviable myocardium.

The primary limitation of CMR metabolic imaging is that the magnetic resonance signals associated with phosphorus-31, creatine, sodium-23, and potassium-39 are much smaller than the proton signal associated with water. The relative low concentration of high-energy phosphate molecules has resulted in low signal-to-noise ratio and a limited sensitivity compared to other techniques. In addition, because of signal dropout as distance away from the surface coil increases, the ³¹P MRS technique can only assess the anterior wall of the left ventricle. These limitations have currently hampered the clinical application of this technique. Higher-field strength MRI (3 T or higher) systems may improve the clinical application of this technique in the future. Future work is needed to compare the relative merits of MRS and CMR imaging techniques.

COMPARISON WITH OTHER NONINVASIVE MODALITIES TO ASSESS MYOCARDIAL VIABILITY OR ISCHEMIA

Currently, there are abundant prognostic data for identifying high-risk patients and assess myocardial viability by the use of scintigraphic techniques (PET and SPECT) and DSE. In general, nuclear perfusion studies have greater sensitivity but lower specificity for identifying viable myocardium compared with techniques that detect contractile reserve (Dob-MRI and DSE).

Dobutamine Stress Echocardiography

Dobutamine stress echocardiography (DSE) is a well-established modality for the diagnosis of myocardial ischemia and viability. Several studies have reported sensitivity, specificity, and accuracy ranging from 54% to 96%, 60% to100%, and 62% to 92%, respectively, in detecting angiographically significant CAD. However, 10% to 15% of patients yield suboptimal or nondiagnostic images, that is, accuracy mainly depends on the experience of diagnostic centers and observers, and test reproducibility is low.⁵⁸ In a study by Nagel et al,⁵⁹ 208 consecutive patients with suspected CAD, DSE and high-dose dobutamine stress magnetic resonance (DSMR, 1.5 T) were performed before cardiac catheterization. With DSMR, sensitivity was increased from 74.3% to 86.2% and specificity from 69.8% to 85.7% (both P < 0.05) compared with DSE. Hundley et al⁶⁰ also performed a high-dose DSMR protocol to test the utility of CMR for the detection of ischemia in 153 patients who were not well suited for stress echocardiography because of poor acoustic windows and reported a sensitivity and specificity of 83% for the detection of a coronary stenosis greater than 50% of the luminal diameter. However, the additional use of myocardial tagging to DSMR increased diagnostic accuracy and the number of positive dobutamine-CMR studies, with 17% in the study of Kuijpers et al.⁶¹ In a study of 327 patients with an in conclusive diagnosis of myocardial ischemia,⁶² 214 (99%) patients had a negative DSMR with an average follow-up of 24 months. Patients with a DSMR study and regional wall motion abnormality showed a significantly higher annual major adverse cardiac event rate (18%) than the patients without regional wall motion abnormality (0.56%; P < 0.001). Patients without regional wall motion abnormality showed an annual event rate of 2% when they had a history of CAD and less than 0.1% without a previous coronary event (P < 0.001). Dobutamine stress magnetic resonance showed a positive and negative predictive value of 95% and 93%, respectively. Sensitivity was 96%, and specificity 95%. The results of contractile response with dobutamine protocols are essentially identical in most studies for both DSMR and DSE. Therefore, it is reasonable to extrapolate the data regarding the extensive prognostic data available for DSE to DSMR.^31,63,64

Single-Photon Emission Computed Tomography

Although SPECT imaging has been the most commonly used clinical tool in assessing patients with symptoms of CAD, its role in assessing myocardial viability has been hampered by limited spatial resolution and insensitivity to viable myocardium. Gunning et al³¹ compared the value of low-dose Dob-MRI, stress/redistribution and separate-day rest/redistribution thallium scintigraphy, and stress/rest tetrofosmin imaging in 30 patients with 3-vessel CAD and significantly depressed LV function (mean LVEF, 24.0%). Late-rest thallium images showed a moderate sensitivity (76%), whereas both stress-redistribution thallium and rest tetrofosmin were insensitive (sensitivity of 68% and 66%, respectively). All 3 tracer techniques were nonspecific (44%, 51%, and 49%, respectively). In comparison, although dobutamine-induced contractile response by CMR was also insensitive (50%) in recruiting segmental wall thickening in preexisting resting dysfunction, low-dose dobutamine challenge simulates a physiologic process (increased regional blood flow and myocyte inotropy) and was able to offer a high specificity (81%) in its prediction of regional functional improvement. On the other hand, it has been consistently shown that CMR detects subendocardial infarcts routinely missed by SPECT. Mahrholdt et al⁶⁵ compared LGE with SPECT in 91 patients and also evaluated against histologically confirmed transmural or subendocardial infarctions in dogs. Histologically confirmed subendocardial infarcts were detected by LGE in 92% and by SPECT in 28%. Almost 50% of the subendocardial infarcts were missed by SPECT as compared with LGE. Gutberlet et al⁶⁶ compared LGE, dobutamine stress CMR, end-diastolic wall thickness, and thallium-201 SPECT in 20 patients with significant impairment of LV systolic function (mean [SD] ejection fraction, 29% [9]) both before and 6 months after coronary artery bypass grafting. Late gadolinium enhancement performed best with the highest sensitivity (99%) and specificity (94%) for viability, whereas SPECT retained a high sensitivity (86%) but demonstrated low specificity (68%). The combination of contractile response from low-dose dobutamine and transmural extent of LGE by CMR offers a powerful combination in providing superior sensitivity and specificity for the detection of myocardial viability compared to SPECT imaging. Our group has demonstrated the strong prognostic implication of LGE in patients without prior knowledge of MI. In a study involving 195 patients with suspected CAD but without prior documented MI, patients who were found to have LGE even in the lowest tertile range, on average involving as little as less than 2% of the total LV mass, experienced a greater than 7-fold increase in hazards to composite adverse cardiac outcomes including death (Fig. 3). The presence of LGE scar was the strong predictor to adverse cardiac outcomes and provided incremental prognostic value beyond robust clinical parameters such as LVEF and end-systolic LV sizes (Figs. 4 and 5).

FIGURE 3: Strong prognostic association of the myocardial extent by LGE with patient adverse cardiac event. In a study of 195 patients who had no history of MI and referred with a suspicion of CAD, a presence of LGE even in the lowest tertile extent portended to a more than 7-fold elevation of hazard to adverse cardiac events.

FIGURE 4: Case 1: A patient with atypical chest pain was referred for assessment of myocardial ischemia. On LGE imaging, a focal endocardial infarction is seen in the midanterior wall. This subendocardial infarction was not detected by regional wall motion imaging.

FIGURE 5: Case 2: A patient with a history of anterior MI presented to the hospital with chest pain. On LGE imaging, a large "gray zone" is seen adjacent to the LGE core. In a single-center study, this imaging technique, which characterized the intermediate signal intensity "gray zone," has demonstrated a strong association with post-MI mortality and provided incremental prognostic value beyond LVEF.

Positron Emission Tomography

Positron emission tomography offers the combination of perfusion and metabolism imaging using FDG and has been the reference standard of viability imaging for the past decades. Several studies have shown a good correspondence between ¹⁸F FDG-PET and dobutamine-induced systolic wall thickening for the identification of dysfunctional but viable myocardium.^29,67 Schmidt et al⁶⁸ designed a study to extend previous observations by adding information about functional recovery 4 to 6 months after successful revascularization in patients with patent vessels supplying the dysfunctional infarct region. Positive and negative predictive values and diagnostic accuracy were 78%, 100%, and 83% for preserved end-diastolic wall thickness; 92%, 93%, and 93% for dobutamine-inducible contraction reserve; and 86%, 100%, and 90% for preserved ¹⁸F FDG uptake. Klein et al⁶⁹ found a close correlation between the extent of myocardial scar identified by LGE and PET in 31 patients with ischemic cardiomyopathy. Quantitative assessment of infarct mass by LGE correlated well with PET infarct size. One of the most intriguing findings in their study was that LGE identified subendocardial scarmore frequently than PET. More than half of the segments with subendocardial scar identified by CMR were not detected by ¹⁸F-FDG PET. They also compared LV wall thickness and thickening at rest in combination with LGE for viability, with PET as the criterion standard, and found significantly better results for LGE. Knuesel et al⁷⁰ applied PET and CMR in ischemic chronic LV dysfunction to relate metabolism and tissue composition to changes of contractile function after revascularization. In their study, 19 patients with MIs were observed by magnetic resonance after revascularization: 85% of segments with preserved FDG uptake and a thick rim of viable tissue on magnetic resonance recover function after revascularization, whereas only 13% of metabolically nonviable segments (FDG uptake <50%) with a thin rim of viable tissue on magnetic resonance recover function. Segments with either reduced FDG uptake or a thin rim of viable tissue on magnetic resonance show a reduced probability for functional recovery (36% and 24%, respectively). Kuhl et al,⁷¹ using CMR, quantitatively analyzed the segmental extent of scar tissue and, using PET, compared it with segmental FDG uptake. They found that nonviable segments by FDG-PET demonstrate a significantly larger extent of hyperenhancement compared with segments identified as viable by FDG-PET. Whereas a cutoff value of37% segmental extent of hyperenhancement was identified to differentiate nonviable from viable myocardium with optimal combination of sensitivity and specificity, a threshold of 50% improved the specificity of detecting nonviable myocardium, thereby increasing the amount of segments scored viable by CMR. The same group⁷² concluded in a later study that CMR is comparable with a PET/SPECT imaging protocol for the prediction of regional and global functional improvement after revascularization. Twenty-nine patients with ischemic cardiomyopathy were investigated using CMR and PET/SPECT. Sensitivity and specificity for the prediction of functional recovery at follow-up 97% and 68% for CMR and 87% and 76% for PET/SPECT, respectively. Although the positive predictive value for functional recovery was identical for both techniques (73%), CMR achieved a higher negative predictive value (93% vs 77%, respectively), indicating that CMR is superior to PET/SPECT for the identification of segments unlikely to recover function after revascularization. Collectively, current evidence suggests that visualizing viable myocardium alone by nuclear techniques, albeit high sensitivity by PET, does not fully represent the complete spectrum of segmental viability. The ability to characterize infarcted myocardial thickness and presence of sub endocardial infarction at high-spatial resolution and contrast-to-noise ratio may offer incremental accuracy in viability assessment and patient risk stratification.

CONCLUSIONS

By a combination of cine imaging, stress testing, and delayed hyperenhancement, CMR imaging is a unique method for complete noninvasive assessment of myocardial viability and ischemia. Given the growing prognostic implication and continual technical improvement, CMR is expected to assume an increasing role in patient risk stratification and management.