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Journal of the American College of Cardiology Vol. 59, No. 4, 2012© 2012 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00

STATE-OF-THE-ART PAPER

Imaging in the Management of Ischemic CardiomyopathySpecial Focus on Magnetic Resonance

Andreas Schuster, MD,* Geraint Morton, MA, MBBS,* Amedeo Chiribiri, MD, PHD,*Divaka Perera, MD,* Jean-Louis Vanoverschelde, MD, PHD,† Eike Nagel, MD, PHD*

London, United Kingdom; and Brussels, Belgium

Heart failure of ischemic origin has become increasingly common over the last decade because of the improvedsurvival of patients with acute myocardial infarction. Revascularization with coronary bypass grafting or percuta-neous coronary intervention plays a pivotal role in patients with ischemic cardiomyopathy, although these inter-ventions are often associated with relatively high peri-procedural risk. The pathophysiological substrate of isch-emic cardiomyopathy is heterogeneous, varying from predominantly hibernating myocardium to irreversiblescarring. There is evidence to suggest that patients with hibernating myocardium benefit most from revascular-ization, whereas medical therapy is associated with an adverse prognosis. Therefore, noninvasive testing is rec-ommended by relevant guidelines to guide optimal management in these patients. However, the role of noninva-sive testing has recently been challenged. There are various imaging modalities available that provideinformation on different aspects of the disease, and therefore, they differ significantly in sensitivity and specific-ity. In clinical practice, choosing among the different imaging modalities can be difficult. Cardiac magnetic reso-nance has evolved into a comprehensive modality that can accurately determine the amount of hibernatingmyocardium as well as the presence and degree of myocardial ischemia and the extent of the scar. This paperreviews the indications, accuracy, and clinical utility of the available imaging techniques, with a special focus oncardiac magnetic resonance in ischemic cardiomyopathy, and provides an outlook on how this field might evolvein the future. (J Am Coll Cardiol 2012;59:359–70) © 2012 by the American College of Cardiology Foundation

Published by Elsevier Inc. doi:10.1016/j.jacc.2011.08.076

Heart failure and myocardial infarction secondary to coro-nary artery disease (CAD) constitute leading causes of death(1). Despite recent advances in therapy, ischemic cardiomy-opathy (ICM) is associated with high mortality, and deter-mining the best management is challenging. In patientswith normal ejection fraction (EF), prognosis in CAD isassociated with the ischemic burden and the amount ofischemia reduction achieved by therapy (2), as well as thepresence or absence of hibernating myocardium (2,3). How-ever, the former has not been specifically shown for patientswith reduced EF.

The definition of ICM is inconsistent. Some trials,including the STICH (Surgical Treatment for Ischemic

From the *Division of Imaging Sciences and Biomedical Engineering, King’s CollegeLondon British Heart Foundation Centre of Excellence, National Institute of HealthResearch Biomedical Research Centre at Guy’s and St. Thomas’ NHS FoundationTrust, Wellcome Trust and Engineering and Physical Sciences Research CouncilMedical Engineering Centre, The Rayne Institute, St. Thomas’ Hospital, London,United Kingdom; and the †Division of Cardiology, Cliniques Universitaires St. Luc,Brussels, Belgium. This work was supported by the BHF (RE/08/003�FS/10/029/28253 to Drs. Schuster, Perera, and Nagel), the BRC (BRC-CTF 196 toDrs. Schuster, Perera, and Nagel), and a European Union grant (224495 to Drs.Morton and Nagel). Dr. Nagel has received significant grant support from BayerSchering Pharma and Philips Healthcare. All other authors have reported thatthey have no relationships relevant to the contents of this paper to disclose.

Manuscript received April 21, 2011; revised manuscript received July 18, 2011,accepted August 2, 2011.

Heart Failure) trial, defined it as a severe reduction of leftventricular (LV) function (�35%) (4,5), whereas others usean LV function �50% in the presence of severe CAD (3,6).For this review, we use the latter definition. The pathophys-iological substrate of ICM is heterogeneous, varying frompredominantly hibernating myocardium to irreversible scar-ring. The concept of “hibernating myocardium” refers tomyocardium that is supplied by a diseased coronary arteryand is ischemic and dysfunctional but remains alive and thushas the potential to regain contractility after revasculariza-tion. There are different definitions of hibernating myocar-dium. The most accepted definition is an improvement incontractility after revascularization. Even though this defi-nition is the most accurate, it is only after revascularizationthat the diagnosis can be made (i.e., it is a retrospectivedefinition [7,8] and thus not useful for clinical decisionmaking). Therefore, all diagnostic tests use surrogate defi-nitions to assess the presence of hibernating myocardium.These definitions vary, and different imaging techniquesprovide information on different aspects of the pathophys-iology such as metabolic imaging, scar imaging, or contrac-tile reserve. Consequently, the results may depend on thechosen imaging test.

Even though there is less evidence, the importance of an
additional ischemic component to the presence of hibernat-

360 Schuster et al. JACC Vol. 59, No. 4, 2012Noninvasive Imaging in Ischemic Cardiomyopathy January 24, 2012:359–70

ing myocardium has been in-creasingly recognized (9). Be-cause the relative importance ofthe ischemic component has notbeen fully established and differ-ent imaging strategies yield dif-ferent results, it remains difficultto decide which test is clinicallymost suitable and which param-eter most important in a givenpatient.

Hibernating Myocardium

The observation of dysfunctionalmyocardium regaining function af-ter coronary artery bypass grafting(CABG) (10) led to the introduc-tion of “hibernation” (11) and wasrelated to reduced coronary bloodflow (12).

Hibernating myocardium re-fers to a progressive and dynamiccondition of chronic abnormallycontracting myocardium, withfunction that improves after re-vascularization. The exact patho-physiology is still controversial.Dysfunction initially is probablycaused by reduced flow reserve

leading to ischemic episodes during stress (13). Myocardialischemia rapidly impairs contractile function, which maypersist for several hours after reperfusion (myocardial stun-ning), and its repetitive occurrence might lead to chronicdysfunction even when perfusion at rest is still normal (14).This is referred to as “perfusion-contraction mismatch.” Overtime, perfusion at rest will decrease, leading to a restitution ofperfusion-contraction matching (15). In parallel with this,increased fibrosis and myocyte alterations (degeneration andapoptosis) occur, reducing the likelihood of complete func-tional recovery after revascularization (Fig. 1).

Patients with hibernating myocardium (by any diagnostictest) have been shown to have a significant survival advan-tage following revascularization compared with those re-ceiving medical therapy alone. Allman et al. (3) presented ameta-analysis pooling the data of 3,088 patients from 24studies between 1992 and 1999. Hibernating myocardiumwas determined using single-photon emission computedtomography (SPECT), positron emission tomography(PET), or dobutamine stress echocardiography (DSE) witha 2-year follow-up. A strong association was found betweenhibernating myocardium identified with noninvasive testingand improved survival after revascularization. Revasculariza-tion was associated with a nearly 80% reduction in mortalityin patients with hibernating myocardium (16% with medical

Abbreviationsand Acronyms

CABG � coronary arterybypass grafting

CAD � coronary arterydisease

CMR � cardiac magneticresonance

CT � computer tomography

DSE � dobutamine stressechocardiography

DSMR � dobutaminestress magnetic resonance

EF � ejection fraction

FFR � fractional flowreserve

ICM � ischemiccardiomyopathy

LGE � late gadoliniumenhancement

LV � left ventricular

MCE � myocardial contrastechocardiography

PET � positron emissiontomography

SPECT � single-photonemission computedtomography

therapy vs. 3.2% with revascularization). Conversely, in the

absence of hibernating myocardium, there was no differencein mortality with revascularization (7.7%) versus medicaltherapy (6.2%).

Camici et al. (16) more recently pooled the data from 14nonrandomized studies, published between 1998 and 2006,that reported long-term Kaplan-Meier survival curves. Theyalso found a survival benefit associated with revasculariza-tion compared with medical treatment in patients withhibernating myocardium but no benefit in those without.Interestingly, and in apparent contradiction to Allman et al.(3), the annual mortality rate in patients treated medicallyappeared to be independent of the presence of hibernatingmyocardium. Whether this contradiction might be ex-plained by optimized patient care due to improved medicaltherapy including implantable cardioverter defibrillators or ahigher revascularization rate in patients with significantamounts of hibernating myocardium remains speculative.The main disadvantage of both studies is their retrospectivenature and the lack of randomization.

The long-awaited STICH trial is a prospective, random-ized, multicenter outcome study comparing 1,212 patientswith ICM (EF �35%) assigned to intensive medical ther-apy with patients assigned to intensive medical therapy andCABG (4). There was no significant difference with respectto the primary endpoint of death from any cause (4).

A prospective substudy in 601 patients investigated whetherassessment of hibernating myocardium (with SPECT and/orDSE) can identify patients who would benefit most fromrevascularization (5). A total of 298 patients were assigned tointensive medical therapy and CABG, and 303 were assignedto receive intensive medical therapy alone. Thirty-seven per-cent of patients with hibernating myocardium and 51% ofpatients without hibernating myocardium died during follow-up. After adjustment for differences in baseline variables andrisk factors, there was no significant association of hibernatingmyocardium with mortality. Furthermore, patients with hiber-nating myocardium who were assigned to CABG plus medicaltherapy did not have improved survival compared with thoseassigned to medical therapy alone. Unfortunately, several lim-itations of this trial must be considered. 1) Assessment ofhibernating myocardium was performed only in those STICHpatients when investigators had the test available and activelyreferred the patient. It is unclear whether this referral wasrandom or related to clinical factors. 2) There was an imbal-ance between patient groups because 81% of all patients hadsignificant hibernating myocardium (leaving 19% without hi-bernating myocardium). 3) To be classified as a patient havingsignificant hibernating myocardium, 65% of the myocardiumhad to be hibernating with SPECT (�11 segments) or 31% ofthe myocardium had to be hibernating with DSE (�5 seg-ments). In addition, hibernating territories were not related tothe coronary anatomy. Both factors may compound interpre-tation of these findings. 4) Hibernating myocardium wasassessed with SPECT or DSE, neither of which is consideredto be the gold standard tool for this investigation. In contrast,
the retrospective analyses that demonstrated improved survival

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361JACC Vol. 59, No. 4, 2012 Schuster et al.January 24, 2012:359–70 Noninvasive Imaging in Ischemic Cardiomyopathy

after revascularization also included PET (3) and cardiacmagnetic resonance (CMR) (16). 5) Patients in the medicaltherapy arm of the trial had a significantly higher rate of aspirinand statin use at baseline compared with patients who under-went CABG, which may have improved survival in themedical therapy group.

Current guidelines recommend noninvasive testing be-fore revascularization (17). This may be subject to changebased on the STICH trial. However, there is still a need forwell-defined prospective outcome studies using state-of-the-art noninvasive testing to plan revascularization inpatients with ICM.

Ischemia

The role of inducible ischemia in ICM is less well estab-lished than the role of hibernating myocardium.

In patients with stable, symptomatic CAD and preservedEF, revascularization only confers a prognostic benefit(reduced rate of death, nonfatal myocardial infarction, andrepeat revascularization) if patients have significant myocar-dial ischemia (as assessed by fractional flow reserve [FFR]),whereas revascularization of stenoses not limiting flow has anegative effect on prognosis. The role of “medical therapyonly,” however, was not clarified in this study (18). Vaso-

Figure 1 Development of Ischemic Cardiomyopathy as a Time-D

At a pathophysiological level, there are 3 different phenomena contributing: 1) initcontractile function; 2) over time, there will eventually be a decrease in resting pestate of hibernating myocardium; and 3) there is further disease progression withof functional recovery following revascularization diminishes as the disease progreno recovery later (late second to third stage).

dilator stress CMR correlates well with FFR (19) and can be d

used as a noninvasive alternative to FFR in similar patientsto identify individuals at high risk for cardiac death, nonfatalmyocardial infarction, or congestive heart failure (20).

It is unknown whether this holds true in patients withICM with or without hibernating myocardium. Rizzello etal. (9) examined 128 consecutive patients with DSE beforerevascularization and showed that the presence of ischemiadid not add significantly to predicting outcome, whereas theextent of hibernating myocardium was a strong predictor oflong-term prognosis. In contrast, Pasquet et al. (21) re-ported that ischemia as determined by 201thallium-SPECT

as an important predictor of outcome in patients withhronic left ventricular dysfunction. They prospectivelyssessed hibernating myocardium and ischemia in 137onsecutive patients who underwent 201thallium-SPECT

and DSE with a follow-up of 3 years and reconfirmed theprognostic value of revascularization in patients with hiber-nating myocardium. In addition, they found improvedsurvival in patients with ischemic myocardium (as deter-mined by 201thallium-SPECT) who underwent revascular-zation independent of the presence of hibernating myocar-ium (21). Interestingly and in line with Rizzello et al. (9),hey did not show a relationship between ischemia assessedy high-dose DSE and prognosis. It is unclear whether this

dent Phenomenon

petitive episodes of stunning result in a mismatch between oxygen delivery and(oxygen delivery), restoring the perfusion/contraction balance and leading to the

s and myocyte alterations marking the end stage of the disease. The likelihoodwith a high likelihood of recovery early (first to early second stages) and little to

epen

ially rerfusionfibrosisses,

ifference can be explained by the different pathophysiolo-

aphy; St

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gies tested (i.e., DSE reflects oxygenation on a cellular level,whereas 201thallium-SPECT reflects cellular integrity com-bined with flow) or possible technical limitations of DSE,which might suffer from poor acoustic windows anddifficult endocardial border delineation, especially inpatients with ICM. The findings also need to be inter-preted in the context of the relatively small study popu-lation and the unblinded, nonrandomized study design. Itremains unclear to date whether ischemia is an importantparameter in patients with ICM. Given the controversialresults of the STICH trial and the lack of data onischemia testing in ICM, there is a clear need forprospective outcome studies investigating the relativeimportance of both ischemia and hibernating myocar-dium, preferably in a multicenter setting.

Surrogate Measures of Hibernating MyocardiumTable 1 Surrogate Measures of Hibernating Myocardium

Modalities and Targets Metabolism Perfu

CMR � �

CT � �

Echocardiography � �

PET � �

SPECT � �

Assessment of functional integrityof myocardial cells

Detection of blothe myocard

CMR � cardiac magnetic resonance; CT � computed tomography; PET � positron emission tomogrhis assessment.

Characteristics of Hibernating MyocardiumTable 2 Characteristics of Hibernating Myocardium

Imaging Technique Imaging Target

Echocardiography Contractile reserve (dobutamine stress echocardiograph

Perfusion (MCE)

Scarring (MCE)

SPECT Contractile reserve (dobutamine-gated SPECT)

Perfusion intact cell membrane (201thallium-SPECT)

Perfusion intact cell membrane/intact mitochondria(99mtechnetium-tetrofosmin/MIBI SPECT)

Free fatty acid metabolism (123I-BMIPP SPECT)

Glucose metabolism (18FDG-SPECT)

PET Perfusion (13NH3-labeled ammonia, 15O2-labeled water,and 82Rb-labeled PET) (71)

Glucose metabolism (FDG-PET)

CMR Perfusion (perfusion CMR)

Oxygenation (high-dose DSMR)

Contractile reserve (low-dose DSMR)

Scarring (LGE-CMR)

Oxygenation (blood oxygen level–dependent CMR)

CT Perfusion

Scarring (DE-CT)

Integrated PET-CT andSPECT-CT

Combined DE-CT and perfusion PET (13NH3 and 15O2 PE

*Myocardium at risk for significant ischemia.
BMIPP � �-methyl-p-iodophenyl-pentadecanoic acid; DE � delayed enhancement; DSMR � dobutamiCE � myocardial contrast echocardiography; MIBI � methoxyisobutylisonitrile; other abbreviations as i
Clinically, a single test that provides assessment of thepresence and extent of hibernating myocardium and thepresence and severity of ischemia seems most appropriate toguide therapy. The current evidence is, however, not ade-quate to direct clinicians toward either an ideal diagnostictest or toward understanding the relative importance ofischemia versus hibernating myocardium in patients withICM (22).

LV Function

Impaired LV function is associated with adverse prognosis(23). The potential survival benefit in patients with hiber-nating myocardium who undergo revascularization may wellbe mostly explained by improved global LV function afterrestoration of blood flow. Bax et al. (24) pooled data from

Nonviability Scar Contractile Reserve

� �

� �

(�) �

� �

� (�)

w toward Exact localization and size ofnecrosis/fibrosis

Assessment of contractile function

PECT � single-photon emission computed tomography; (�) � technique potentially useful to make

Definition of Hibernating Myocardium

Improvement in contraction (visual or quantitative analysis using strain rate [69])

Homogenous contrast enhancement during rest steady-state perfusion (35)

Contrast agent uptake visualized with 3-dimensional echocardiography (36)

Improvement in contraction (70)

Tracer uptake �50%

Tracer uptake �65%

Preserved glucose metabolism

Irreversible injury: flow metabolism match; ischemic but viable:flow metabolism mismatch

Irreversible injury: defect with stress and at rest;Myocardium at risk*: inducible defect with stress and not at rest

New wall motion abnormalities with stress reflect cellular hypoxia

Improvement in function

Gadolinium uptake visualized in LGE images



Iodine contrast agent uptake visualized in late enhancement images

Anatomy of coronary arteries, ischemia, and hibernating myocardium

sion

od floium

y)

T)

ne stress magnetic resonance; FDG � fluorodeoxyglucose; LGE � late gadolinium enhancement;n Table 1.


Figure 2 Pathophysiological Targets of Different Imaging Methods

201Thallium–single-photon emission computed tomography (SPECT) depends on intact cellular membranes and energy-dependent uptake via the Na�K�-antiporter. Technetium-labeled tracers tetrofosmin (TF) and methoxyisobutylisonitrile (MIBI) are lipophilic cations that can be imaged with SPECT after passively crossing the mitochondrial membranes(driven by the transmembrane electrochemical gradient), where they are retained. Dobutamine targets �1 and �2 adrenoreceptors (�-AR), leading to increased intracellular Ca2�

and positive inotropy. Responses to dobutamine stress are mainly imaged with dobutamine stress echocardiography and dobutamine stress magnetic resonance. 18-fluorode-oxyglucose (18FDG) targets glucose metabolism and is mainly imaged with positron emission tomography (PET) after uptake via the glucose transporter uniporter. FDG is intra-cellularly phosphorylated by hexokinase to FDG-6-phosphate, which is not further used in glycolysis or glycogen synthesis. 82-Rubidium (82Rb)-PET depends on intact cellularmembranes and energy-dependent uptake via the Na�-K�-antiporter similarly to 201thallium. 13NH3-PET depends on passive diffusion or on the active Na�-K�-antiporter mecha-nism. H2

15O diffuses freely through the membrane and reaches equilibrium between extravascular and intravascular compartments. Gadolinium is an extracellular contrastagent that passively diffuses into the extracellular space. When the extracellular space is significantly increased (e.g., after cell membrane rupture in acute myocardial infarctionor in collagenous subendocardial scar as shown in this case), gadolinium accumulates and is retained due to altered wash in/wash out kinetics and can then be imaged withlate gadolinium enhancement–cardiac magnetic resonance imaging.

Figure 3 Diagnostic Accuracy of Different Techniques to Assess Hibernating Myocardium

Although an increase in global ejection fraction (EF) after revascularization is associated with improved prognosis in patients with ICM, most studies have evaluated theimpact of revascularization on improvement of regional function of hibernating myocardium rather than global improvement of function. The black line represents lategadolinium enhancement–cardiac magnetic resonance (LGE-CMR) as a reference standard for nonviability. The individual percentage terms refer to the extent of trans-murality of scar. Although techniques addressing hibernating myocardium by looking at cellular integrity lie on or close to the LGE accuracy line (16,74), techniques look-ing at contractile reserve reach a higher accuracy (16,48), which can be even further increased by applying quantitative wall motion analysis techniques such as strain(51,75). DSE � dobutamine stress echocardiography; DSMR � dobutamine stress magnetic resonance; other abbreviations as in Figures 1 and 2.

F


105 studies that used SPECT, PET, or DSE to predictregional or global recovery. An improvement in global EFwas detected in 28 studies. In the presence of hibernatingmyocardium, LVEF improved (from 37% to 45%), whereasin the absence of hibernating myocardium, EF remainedunchanged (36%). Patients with an improvement in LVEFafter revascularization have an improved prognosis (25).When considering revascularization, it is important to notethat even if regional wall motion remains unchanged, globalfunction may improve (26).

Noninvasive Functional Assessment

There are several imaging modalities assessing 3 main surro-gate parameters of hibernating myocardium (Tables 1 and 2,

Positron Emission TomographyTable 3 Positron Emission Tomography

Target Tracer

Perfusion Perfusion tracer (15O2, 13NH3, 82Rb) Detection of bcompetent

Hibernating myocardium Metabolism tracer FDG(used in combination withperfusion tracer 13NH3)

Metabolism: Fby hexokinwhich is noglycogen sy

Abbreviation as in Table 2.

Single-Photon Emission Computed TomographyTable 4 Single-Photon Emission Computed Tomography

Tracer Biological Properties201Thallium Similar to potassium

(monovalent cation)1. Initial tra

perfusion2. Sustained

3–4 h afcell memreflects h

99Technetium metastabletetrofosmin and MIBI

Lipophilic cations Similar flowhigher encompareless radi

123I-BMIPP Radioiodine-labeled fatty acid tracer Metabolic impersistenincreasetriglyceri

18FDG* Glucose analogue positron emitter Metabolic im

*With the introduction of 511 keV collimators, 18FDG is being increasingly used for SPECT imaging
DG is originally a PET tracer.CAD � coronary artery disease; other abbreviations as in Tables 1 and 2.
Fig. 2) (27): 1) myocardial metabolism with functionalintegrity of cells and mitochondria; 2) nonviable tissue bydetermining the localization and extent of necrosis orfibrosis; and 3) contractile reserve during inotropic stimu-lation. Different imaging modalities measure different as-pects of physiology and pathophysiology, resulting in dif-ferent accuracies (Fig. 3).PET and SPECT. PET imaging is well validated, andmetabolism-perfusion mismatch has high negative and pos-itive predictive values (Table 3) (28). With PET, myocardialperfusion and metabolism can be fully quantified, a poten-tial advantage compared with SPECT or DSE. Further-more, PET is associated with outcome: A post hoc analysis,PARR-2 (PET and Recovery Following Revascularization-2),

Kinetics Protocols

ow throughls

1. Rest perfusion: first bolus injection

2. Stress perfusion: acquisition 5 half-times afterrest scan after second injection duringvasodilator stress

intracellularly phosphorylatedFDG-6-phosphate,er used in glycolysis oris

1. Rest perfusion

2. Metabolic imaging

Kinetics Protocols

ake dependent on regional

e (usually imagedction) dependent onintegrity, whichting myocardium (72)

1. Stress: reversible defect from peak stress todelayed “redistribution” (3–4 h or 24 h afterinjection) is marker of reversible ischemia inhibernating myocardium

2. Rest: reversible defect at redistribution indicateshibernating myocardium with restinghypoperfusion; fixed defects reflect scar tissue

3. Reinjection: in case of limited initial uptake duringstress in severe CAD, a “fixed” defect might bepresent in hibernating myocardium because201Tl is normally cleared from blood pool rapidly;second “reinjection” of small dose of 201Tl at restis necessary to proof hibernating myocardiumafter the redistribution images

cs but emission ofnd shorter half-life201Tl (better detection and

Retention in mitochondria with minimalredistribution requires separate injection at restand stress; information about perfusion andhibernating myocardium; dysfunctional segmentswith tracer uptake �65% are consideredhibernating

related toase in �-oxidation with

t retention of BMIPP inl

Assessment of hibernating myocardium and“ischemic memory”; after ischemic episode,fatty acid metabolism may be suppressed forprolonged time, and BMIPP imaging candemonstrate regional metabolic defect even ifperfusion has returned to normal

of glycolysis Hibernating myocardium shows preserved or evenrelatively higher glucose metabolism comparedwith flow; principle referred to as metabolism-perfusion mismatch

al data have shown excellent agreement between SPECT and PET for FDG imaging (73); however,

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showed that revascularization improved outcome in patientswith ICM and a myocardial perfusion-metabolism mis-match of �7% and did not in those with �7% (29).

SPECT has been a cornerstone of noninvasive imagingfor many years. Myocardial perfusion and hibernatingmyocardium can be assessed from tracer uptake andredistribution specifically targeting cell membrane integ-rity and mitochondrial function (Table 4, Fig. 2). Othertracers targeting �-oxidation and assessment of function

ith low-dose dobutamine are available, but their clinicaltility has not been sufficiently established (Table 4) (30).he main disadvantages of PET and SPECT remain

heir radiation exposure and relatively low spatial resolution.chocardiography. Echocardiography is widely avail-ble, fast, relatively cheap, and therefore frequently usedrst line. Although improved function with low-doseobutamine indicates hibernating myocardium (31,32),he occurrence of new wall motion abnormalities atigher stress levels or a biphasic response are considerediagnostic of inducible myocardial ischemia. Myocardialontrast echocardiography (MCE) further improves theccuracy to detect regional wall motion abnormalities33). MCE has also been proposed for the detection ofnducible myocardial ischemia during vasodilator stressnd might evolve as an alternative to DSE for thessessment of ischemia (Table 5) (34,35). Quantificationf myocardial blood flow using MCE is accurate for the

EchocardiographyTable 5 Echocardiography

Modality Target

MCE Perfusion, hibernating myocardium(microcellular integrity), and scar

Destruction (bultrasoundvelocity ofmicrobubb

Scar imaging (MCE) Scar Contrast agenwith 3-dime

DSE Biphasic response: contractilereserve and ischemia

Acquisition ofand variou

DSE � dobutamine stress echocardiography; MCE � myocardial contrast echocardiography; othe

Cardiovascular Magnetic ResonanceTable 6 Cardiovascular Magnetic Resonance

Target Method

Oxygenation DSMR (dobutamine � atropine) Increasing dosato achieve ta

Perfusion Vasodilator (adenosine, dipyridamole) Gadolinium first

Hibernating myocardium DSMR (dobutamine) Low dosages (�

Hibernating myocardium Scar (LGE) Nonviability, ext

Abbreviations as in Tables 1 and 2.

rediction of hibernating myocardium and seems to beuperior to DSE and 201thallium-SPECT (32).

Echocardiography has also been used for the detectionnd quantification of myocardial infarct scars, and goodgreement with late gadolinium enhancement (LGE)MR has been demonstrated (36). However, these recent

dvances need to be confirmed in larger studies. Clini-ally, routine echocardiography frequently suffers fromoor acoustic windows and inadequate endocardial bor-er definition.omputed tomography. Even though computed tomogra-

hy (CT) can be used to assess LV function (37), perfusion38), and scar (Table 2) (39), its main clinical application ismaging of the coronary arteries. Especially in patients withhronic CAD, CT may be limited by high calcium burden.edicated cardiac PET-CT and SPECT-CT systems may

llow for the assessment of coronary artery anatomy and theresence and extent of ischemia and hibernating myocardiumt the same time. Again, this approach might be hampered byigh doses of ionizing radiation, particularly if coronary anat-my, function, hibernating myocardium, and perfusion aretudied (40).

ardiac magnetic resonance. CMR is a comprehensive,ccurate, and increasingly available method to assess pa-ients with ICM and to guide therapy (41). CMR is theeference standard for the assessment of ventricularolume and function and the visualization of scar. It is

hnique Protocols

h mechanical index) and restorationinuously infusedrast agent

1. Stress: replenishment of ultrasound beam aftermicrobubble destruction takes approximately 1 s

2. Rest: replenishment of ultrasound beam aftermicrobubble destruction takes approximately 5 s

3. Scar imaging: increased subendocardial ortransmural brightness

mulation visualizedl echocardiography (36)

Absence of scar in areas where there is hypokinesiaat rest diagnostic of hibernating myocardium

onal images at rests levels

1. Contractile reserve: low dosages of dobutamine(5 to 10 �g·kg�1·min�1)

2. ischemia: �40 �g·kg�1·min�1 plus atropine tomeet target heart rate

viation as in Tables 1 and 2.

Protocols Interpretation

40 �g·kg�1·min�1 � atropine)art rate ([220 � age] � 0.85)

Ischemia can be diagnosed in presence of newwall motion abnormalities on cine CMR

perfusion Induced underperfusion (“perfusion defect”) withstress that is reversible at rest is diagnosticof inducible ischemia

·kg�1·min�1) Increased contractility at low-dose stress inareas where there is hypokinesia at rest isdiagnostic of hibernating myocardium

fibrosis/necrosis Absence of scar in areas where there ishypokinesia at rest is diagnostic ofhibernating myocardium

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highly accurate to assess contractile reserve and ischemiain a single examination without exposure to ionizingradiation. Furthermore, recent registry data showed thatCMR provides an unsuspected new diagnosis in everyfifth referral (42).

The main limitations at this time are the exclusion ofpatients with pacemakers or cardiac resynchronization ther-apy devices and the potential reduction of image quality inpatients with significant arrhythmia or severe shortness of

Figure 4 CMR Scanning Following a Standardized Protocol Rec

The figure shows the different protocols (43) we currently use to assess patientsour standard protocol if the clinical question is mainly hibernating myocardium. Ifor high-dose dobutamine (protocol 3). Although a high-dose dobutamine protocol iswhat higher because of fewer complications. It is important to note that there is cdobutamine stress in patients with low EF. DSMR � dobutamine stress magneticSCMR � Society for Cardiovascular Magnetic Resonance; SSFP � steady-state fre

breath.

CMR of Hibernating Myocardium

Prediction of functional recovery. A basic CMR protocolincludes the assessment of LV volumes and global andregional function (43) based on contiguous short-axis cineimages (44). Different protocols focused on the clinicalquestion are shown in Figure 4. LGE imaging visualizesirreversible damage (myocardial scar or fibrosis) due to anaccumulation of contrast agent in areas with increased

ended by the SCMR

M. Protocol 1 is a basic protocol for ejection fraction (EF) and scar. Protocol 2 isia is also of clinical relevance, we add adenosine stress perfusion (protocol 4)

tly quicker, the feasibility of adenosine perfusion in patients with low EF is some-y no evidence showing the efficacy of adenosine perfusion imaging or high-dosence; HD � high dose; LAX � long axis; LD � low dose; SAX � short axis;ession; other abbreviations as in Figure 1.

omm

with ICischem

slighurrentlresonae prec

extracellular space (Fig. 2) (45). In LGE images, viable


myocardium appears dark, whereas necrotic or fibroticmyocardial tissue appears bright. Myocardium with wallmotion abnormalities at rest but remaining viable tissue isthen regarded as hibernating.

LGE has unprecedented spatial resolution (46) and candetermine the transmural extent of scar and the remainingviable rim, which is not possible with other imagingmodalities. The likelihood of functional recovery can bepredicted based on scar transmurality (45): in the absence ofscar, the likelihood of functional recovery is 78%; if the scarhas more than 75% transmural extent, the likelihood ofrecovery is �2%. However, the value of LGE to predictfunctional recovery in intermediate scars (ranging from 1%to 75% transmurality) is limited, with a likelihood of

Figure 5 Images of a 51-Year-Old Male PatientWith RCA-CTO

CMR showed reduced left ventricular (LV) systolic function (LVEF 45%) at restwith akinesia of the inferolateral wall at basal level. There was nontransmuralscarring (25% to 50%) in the region of the wall motion abnormality. There wasextensive inducible ischemia in the inferior and inferolateral walls with adeno-sine stress, which was not present at rest. The wall motion abnormality in theinferolateral wall at basal level was completely reversible with normal wallthickening during LD-DSMR (arrowheads). RCA-CTO � right coronary arterychronic total occlusion; other abbreviations as in Figures 3 and 4.

approximately 40% (45). In these patients, additional low-

dose dobutamine stimulation can be performed in the sameexamination. Forty-two percent of segments with anintermediate scar show contractile reserve during low-dose dobutamine stimulation (47), and the combinationof contractile reserve and scar quantification leads tooptimal results (48).

The specificity of low-dose dobutamine stress magneticresonance (DSMR) to detect hibernating myocardium issuperior to that of radionuclide methods (49), and endocar-dial and epicardial border definition are superior comparedwith those of echocardiography (50). Potentially sensitivitycould be improved further by the use of myocardial tagging(Fig. 3) (51); however, this potential improvement needs tobe confirmed in a controlled, prospective investigation. Amore recent approach to hibernating myocardium is theassessment of the thickness and function of the remainingnonenhanced viable rim, which can potentially be combinedwith the previously mentioned parameters (52,53).Assessment of prognosis. Prognosis is progressively worsewith increasing amounts of scar (54). Some evidence hassuggested that scar detected by CMR is a stronger predictorof adverse clinical outcome than LVEF and volumes (55).

In patients with fewer than 6 scarred segments, thepresence of scar on LGE images was more accurate forpredicting events than hibernating myocardium assessed bylow-dose DSMR. Conversely, in patients with myocardialscar involving more than 6 segments, hibernating myocar-dium assessed by low-dose DSMR was a better predictor ofevents than scar tissue with LGE (56). Dall’Armellina et al.(57) investigated the relative merit of high-dose DSMR in200 patients with EF �55%. Although DSMR was anindependent predictor of outcome with EF of 40% to 55%,it had no additional value in the presence of EF�40% (57).

From a clinical perspective, a CMR examination includ-ing scar imaging and dobutamine contractile reserve maywell emerge as the gold standard, with the particularadvantage of targeting more than one surrogate parameterof hibernating myocardium. Its accuracy compared withthat of other available techniques to predict functionalrecovery is shown in Figure 3. In general, methods lookingat functional response to stress seem to be more predictivefor functional recovery after revascularization than methodslooking at nonviability (scar) or at cellular integrity.

CMR of Ischemia

Wall motion imaging during high-dose (�40 �g·kg�1·min�1

� atropine) DSMR as well as perfusion imaging duringvasodilator stress are highly accurate for assessing ischemia(Table 6) and are appropriate tests for certain groups withstable angina (8,17,58,59). They are particularly helpful incombination with LGE to determine whether there areareas with ischemia extending beyond irreversibly scarredmyocardium (60).

DSMR mirrors DSE protocols and analyses (50). In
combination with scar imaging, this technique delivers

issprnwicd(a

totm


accurate information on ischemia and hibernating myocar-dium. Quantitative assessment of strain at peak stress ismildly more accurate for ischemia detection than visualanalysis alone (61). This may be of specific importance inpatients with ICM because LV remodeling results incomplex wall motion abnormalities at rest. High-dosedobutamine stress is not recommended in patients with EF�25% due to increased incidence of complications (62).

In addition to being more accurate, quantitative analysisof regional strain or the rapid untwisting of the heart inisovolumic relaxation might allow for the detection ofischemia below peak stress (63), potentially reducing theneed for high-dose dobutamine stress (64).

Advanced first-pass perfusion CMR imaging duringadenosine-induced coronary vasodilation has unprecedentedspatial resolution (�2 � 2 mm or better) and may detectschemia in thinned and remodeled segments. Examples arehown in Figures 5 and 6. However, so far, there are nopecific data on the accuracy of CMR perfusion imaging inatients with heart failure and low EF. Recent publishedeports have been based on patient populations with nearormal EF (20,65) or did not look at subgroups of patientsith different levels of LV function (66). These data may be

mportant because the relatively slow transport of theontrast agent might obscure inducible ischemia. Futureevelopments involve dobutamine stress perfusion imaging67) and measurements of blood oxygenation levels (68) asn alternative to adenosine first-pass perfusion imaging.

An additional advantage of imaging ischemia at the sameime as hibernating myocardium is the potential detectionf inducible ischemia in a coronary artery territory otherhan the territory under investigation for hibernating

Figure 6 Images of a 60-Year-Old Male Patient With RCA-CTO

CMR showed reduced LV systolic function (LVEF 25%) with severe wall motion abnshowed moderate hypokinesia. There was nontransmural scarring (25% to 50%) inAll dysfunctional segments increased wall thickening with low-dose DSMR and shoES � end-systolic; LAD � left anterior descending coronary artery; other abbreviat

yocardium.

Conclusions

Heart failure secondary to chronic CAD is a major problemin clinical cardiology. In patients with inducible ischemiaand hibernating myocardium, revascularization is likely toresult in improvement of regional and global LV function,heart failure symptoms, and long-term prognosis. Guide-lines recommend revascularization in patients with hiber-nating myocardium based on previous evidence suggestingthat patients with hibernating myocardium who weretreated medically have an adverse prognosis. However, theSTICH trial has challenged this view, particularly whenDSE or SPECT is used to define hibernating myocardium.Noninvasive assessment of hibernating myocardium in pa-tients with ICM can guide treatment; however, in light ofthis study, we may need to reconsider the optimal approach.

Various tests are available for identifying hibernatingmyocardium: SPECT imaging is sensitive for detectingcellular integrity and is widely available. DSE is also widelyavailable; however, the sensitivity of this technique is infe-rior, and the prognostic relevance of both SPECT and DSEhave been called into question by the STICH data.

In patients with severely depressed EF, PET imagingmay be useful for assessment of hibernating myocardiumbecause this technique has high sensitivity and superiorresolution to SPECT. Contrast-enhanced CMR in combi-nation with low-dose dobutamine stimulation seems to bethe most accurate technique, with a growing body ofevidence to support it. At this time, we tend to restrict theuse of CMR to more complex patients. Future research willhelp us to better define the relative contribution of ischemiato outcome in patients with hibernating myocardium andthe relative value of the different diagnostic techniques,

evere Proximal LAD Disease

ties at rest predominantly in the anterior wall and the septum. The inferior wallnterior wall, septum (1% to 25%), and inferior wall (1% to 25%; arrowheads).iffuse inducible ischemia with adenosine (arrowheads). ED � end-diastolic;s in Figures 3, 4, and 5.

and S

ormalithe awed dions a

particularly PET and CMR.

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Reprint requests and correspondence: Dr. Andreas Schuster,King’s College London, Division of Imaging Sciences and Bio-medical Engineering, St. Thomas’ Hospital, London, UnitedKingdom. E-mail: [email protected].

REFERENCES

1. Murray CJ, Lopez AD. Alternative projections of mortality anddisability by cause 1990–2020: Global Burden of Disease Study.Lancet 1997;349:1498–504.

2. Shaw LJ, Berman DS, Maron DJ, et al. Optimal medical therapy withor without percutaneous coronary intervention to reduce ischemicburden: results from the Clinical Outcomes Utilizing Revasculari-zation and Aggressive Drug Evaluation (COURAGE) trial nuclearsubstudy. Circulation 2008;117:1283–91.

3. Allman KC, Shaw LJ, Hachamovitch R, Udelson JE. Myocardialviability testing and impact of revascularization on prognosis inpatients with coronary artery disease and left ventricular dysfunction: ameta-analysis. J Am Coll Cardiol 2002;39:1151–8.

4. Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypasssurgery in patients with left ventricular dysfunction. N Engl J Med2011;364:1607–16.

5. Bonow RO, Maurer G, Lee KL, et al. Myocardial viability and survivalin ischemic left ventricular dysfunction. N Engl J Med 2011;364:1617–25.

6. Felker GM, Shaw LK, O’Connor CM. A standardized definition ofischemic cardiomyopathy for use in clinical research. J Am CollCardiol 2002;39:210–8.

7. Patel MR, Dehmer GJ, Hirshfeld JW, Smith PK, Spertus JA.ACCF/SCAI/STS/AATS/AHA/ASNC 2009 appropriateness crite-ria for coronary revascularization. J Am Coll Cardiol 2009;53:530–53.

8. Hendel RC, Berman DS, Di Carli MF, et al. ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 appropriate use criteria forcardiac radionuclide imaging. J Am Coll Cardiol 2009;53:2201–29.

9. Rizzello V, Poldermans D, Schinkel AFL, et al. Long term prognosticvalue of myocardial viability and ischaemia during dobutamine stressechocardiography in patients with ischaemic cardiomyopathy under-going coronary revascularisation. Heart 2006;92:239–44.

10. Rees G, Bristow JD, Kremkau EL, et al. Influence of aortocoronarybypass surgery on left ventricular performance. N Engl J Med1971;284:1116–20.

11. Diamond GA, Forrester JS, deLuz PL, Wyatt HL, Swan HJ.Post-extrasystolic potentiation of ischemic myocardium by atrial stim-ulation. Am Heart J 1978;95:204–9.

12. Rahimtoola SH. A perspective on the three large multicenter random-ized clinical trials of coronary bypass surgery for chronic stable angina.Circulation 1985;72:V123–35.

13. Vanoverschelde JL, Wijns W, Depré C, et al. Mechanisms of chronicregional postischemic dysfunction in humans. New insights from thestudy of noninfarcted collateral-dependent myocardium. Circulation1993;87:1513–23.

14. Wijns W, Vatner SF, Camici PG. Hibernating myocardium. N EnglJ Med 1998;339:173–81.

15. Selvanayagam JB, Jerosch-Herold M, Porto I, et al. Resting myocar-dial blood flow is impaired in hibernating myocardium: a magneticresonance study of quantitative perfusion assessment. Circulation2005;112:3289–96.

16. Camici PG, Prasad SK, Rimoldi OE. Stunning, hibernation, andassessment of myocardial viability. Circulation 2008;117:103–14.

17. Task Force on Myocardial Revascularization of the European Societyof Cardiology (ESC), European Association for Cardio-ThoracicSurgery (EACTS), European Association for Percutaneous Cardio-vascular Interventions (EAPCI), et al. Guidelines on myocardialrevascularization. Eur Heart J 2010;31:2501–55.

18. Tonino PAL, De Bruyne B, Pijls NHJ, et al. Fractional flow reserveversus angiography for guiding percutaneous coronary intervention.N Engl J Med 2009;360:213–24.

19. Lockie T, Ishida M, Perera D, et al. High-resolution magneticresonance myocardial perfusion imaging at 3.0-Tesla to detect hemo-dynamically significant coronary stenoses as determined by fractional
flow reserve. J Am Coll Cardiol 2010;57:70–5.
20. Jahnke C, Nagel E, Gebker R, et al. Prognostic value of cardiacmagnetic resonance stress tests: adenosine stress perfusion and dobut-amine stress wall motion imaging. Circulation 2007;115:1769–76.

21. Pasquet A, Robert A, D’Hondt AM, Dion R, Melin JA, Vanover-schelde JL. Prognostic value of myocardial ischemia and viability inpatients with chronic left ventricular ischemic dysfunction. Circulation1999;100:141–8.

22. Schuster A, Nagel E. Letter by Schuster and Nagel regarding article,“Predicting benefit from revascularization in patients with ischemicheart failure: imaging of myocardial ischemia and viability.” Circula-tion 2011;124:e296.

23. Risk stratification and survival after myocardial infarction. N EnglJ Med 1983;309:331–6.

24. Bax JJ, van der Wall EE, Harbinson M. Radionuclide techniques forthe assessment of myocardial viability and hibernation. Heart 2004;90Suppl 5:v26–33.

25. Rizzello V, Poldermans D, Biagini E, et al. Prognosis of patients withischaemic cardiomyopathy after coronary revascularisation: relation toviability and improvement in left ventricular ejection fraction. Heart2009;95:1273–7.

26. Gerber BL, Darchis J, le Polain de Waroux J-B, et al. Relationshipbetween transmural extent of necrosis and quantitative recovery ofregional strains after revascularization. J Am Coll Cardiol Img 2010;3:720–30.

27. Nagel E, Schuster A. Shortening without contraction: new insightsinto hibernating myocardium. J Am Coll Cardiol Img 2010;3:731–3.

28. Auerbach MA, Schöder H, Hoh C, et al. Prevalence of myocardialviability as detected by positron emission tomography in patients withischemic cardiomyopathy. Circulation 1999;99:2921–6.

29. D’Egidio G, Nichol G, Williams KA, et al. Increasing benefit fromrevascularization is associated with increasing amounts of myocardialhibernation: a substudy of the PARR-2 trial. J Am Coll Cardiol Img2009;2:1060–8.

30. Dilsizian V, Bateman TM, Bergmann SR, et al. Metabolic imagingwith �-methyl-p-[123I]-iodophenyl-pentadecanoic acid identifiesischemic memory after demand ischemia. Circulation 2005;112:2169 –74.

1. deFilippi CR, Willett DL, Irani WN, Eichhorn EJ, Velasco CE,Grayburn PA. Comparison of myocardial contrast echocardiographyand low-dose dobutamine stress echocardiography in predicting recov-ery of left ventricular function after coronary revascularization inchronic ischemic heart disease. Circulation 1995;92:2863–8.

2. Shimoni S, Frangogiannis NG, Aggeli CJ, et al. Identification ofhibernating myocardium with quantitative intravenous myocardialcontrast echocardiography: comparison with dobutamine echocardiog-raphy and thallium-201 scintigraphy. Circulation 2003;107:538–44.

3. Hoffmann R, von Bardeleben S, Kasprzak JD, et al. Analysis ofregional left ventricular function by cineventriculography, cardiacmagnetic resonance imaging, and unenhanced and contrast-enhancedechocardiography: a multicenter comparison of methods. J Am CollCardiol 2006;47:121–8.

4. Kaul S. Myocardial contrast echocardiography: a 25-year retrospective.Circulation 2008;118:291–308.

5. Senior R, Lepper W, Pasquet A, et al. Myocardial perfusion assess-ment in patients with medium probability of coronary artery diseaseand no prior myocardial infarction: comparison of myocardial contrastechocardiography with 99mTc single-photon emission computed to-mography. Am Heart J 2004;147:1100–5.

6. Montant P, Chenot F, Goffinet C, et al. Detection and quantificationof myocardial scars by contrast-enhanced 3D echocardiography. CircCardiovasc Imaging 2010;3:415–23.

7. Raman SV, Shah M, McCarthy B, Garcia A, Ferketich AK. Multi-detector row cardiac computed tomography accurately quantifies rightand left ventricular size and function compared with cardiac magneticresonance. Am Heart J 2006;151:736–44.

8. Blankstein R, Shturman LD, Rogers IS, et al. Adenosine-inducedstress myocardial perfusion imaging using dual-source cardiac com-puted tomography. J Am Coll Cardiol 2009;54:1072–84.

9. Gerber BL, Belge B, Legros GJ, et al. Characterization of acute andchronic myocardial infarcts by multidetector computed tomography:comparison with contrast-enhanced magnetic resonance. Circulation
2006;113:823–33.
mailto:[email protected]

5

6

6

6

6

6

6

6

6

6

6

7

7

7

7

7

7


40. Fazel R, Krumholz HM, Wang Y, et al. Exposure to low-doseionizing radiation from medical imaging procedures. N Engl J Med2009;361:849–57.

41. Morton G, Schuster A, Perera D, Nagel E. Cardiac magneticresonance imaging to guide complex revascularization in stable coro-nary artery disease. Eur Heart J 2010;31:2209–15.

42. Bruder O, Schneider S, Nothnagel D, et al. EuroCMR (EuropeanCardiovascular Magnetic Resonance) registry: results of the Germanpilot phase. J Am Coll Cardiol 2009;54:1457–66.

43. Kramer CM, Barkhausen J, Flamm SD, Kim RJ, Nagel E, Society forCardiovascular Magnetic Resonance Board of Trustees Task Force onStandardized Protocols. Standardized cardiovascular magnetic reso-nance imaging (CMR) protocols. J Cardiovasc Magn Reson 2008;10:35.

44. Hundley WG, Bluemke D, Bogaert JG, et al. Society for Cardiovas-cular Magnetic Resonance guidelines for reporting cardiovascularmagnetic resonance examinations. J Cardiovasc Magn Reson 2009;11:5.

45. Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhancedmagnetic resonance imaging to identify reversible myocardial dysfunc-tion. N Engl J Med 2000;343:1445–53.

46. Wagner A, Mahrholdt H, Holly T, et al. Contrast-enhanced MRI androutine single photon emission computed tomography (SPECT)perfusion imaging for detection of subendocardial myocardial infarcts:an imaging study. Lancet 2003;361:374–9.

47. Kaandorp TAM, Bax JJ, Schuijf JD, et al. Head-to-head comparisonbetween contrast-enhanced magnetic resonance imaging and dobut-amine magnetic resonance imaging in men with ischemic cardiomy-opathy. Am J Cardiol 2004;93:1461–4.

48. Wellnhofer E, Olariu A, Klein C, et al. Magnetic resonance low-dosedobutamine test is superior to SCAR quantification for the predictionof functional recovery. Circulation 2004;109:2172–4.

49. Perrone-Filardi P, Pace L, Prastaro M, et al. Assessment of myocardialviability in patients with chronic coronary artery disease. Rest-4-hour-24-hour 201Tl tomography versus dobutamine echocardiography.Circulation 1996;94:2712–9.

50. Nagel E, Lehmkuhl HB, Bocksch W, et al. Noninvasive diagnosis ofischemia-induced wall motion abnormalities with the use of high-dosedobutamine stress MRI: comparison with dobutamine stress echocar-diography. Circulation 1999;99:763–70.

51. Bree D, Wollmuth JR, Cupps BP, et al. Low-dose dobutaminetissue-tagged magnetic resonance imaging with 3-dimensional strainanalysis allows assessment of myocardial viability in patients withischemic cardiomyopathy. Circulation 2006;114:I33–6.

52. Ichikawa Y, Sakuma H, Suzawa N, et al. Late gadolinium-enhancedmagnetic resonance imaging in acute and chronic myocardial infarc-tion. Improved prediction of regional myocardial contraction in thechronic state by measuring thickness of nonenhanced myocardium.J Am Coll Cardiol 2005;45:901–9.

53. Kirschbaum SW, Rossi A, Boersma E, et al. Combining magneticresonance viability variables better predicts improvement of myocardialfunction prior to percutaneous coronary intervention. Int J Cardiol2011 Mar 15 [E-pub ahead of print].

54. Cheong BYC, Muthupillai R, Wilson JM, et al. Prognostic signifi-cance of delayed-enhancement magnetic resonance imaging: survivalof 857 patients with and without left ventricular dysfunction. Circu-lation 2009;120:2069–76.

55. Roes SD, Kelle S, Kaandorp TAM, et al. Comparison of myocardialinfarct size assessed with contrast-enhanced magnetic resonance im-aging and left ventricular function and volumes to predict mortality inpatients with healed myocardial infarction. Am J Cardiol 2007;100:930–6.

56. Kelle S, Roes S, Klein C, et al. Prognostic value of myocardial infarctsize and contractile reserve using magnetic resonance imaging. J AmColl Cardiol 2009;54:1770–7.

57. Dall’Armellina E, Morgan TM, Mandapaka S, et al. Prediction ofcardiac events in patients with reduced left ventricular ejection fractionwith dobutamine cardiovascular magnetic resonance assessment of wallmotion score index. J Am Coll Cardiol 2008;52:279–86.

58. Hendel RC, Cerqueira M, Douglas PS, et al. A multicenter assess-ment of the use of single-photon emission computed tomography

myocardial perfusion imaging with appropriateness criteria. J Am CollCardiol 2010;55:156–62.

9. Skinner JS, Smeeth L, Kendall JM, Adams PC, Timmis A, GroupCPGD. NICE guidance. Chest pain of recent onset: assessment anddiagnosis of recent onset chest pain or discomfort of suspected cardiacorigin. Heart 2010;96:974–8.

0. Plein S, Kozerke S, Suerder D, et al. High spatial resolution myocar-dial perfusion cardiac magnetic resonance for the detection of coronaryartery disease. Eur Heart J 2008;29:2148–55.

1. Kuijpers D, Ho KY, van Dijkman PR, Vliegenthart R, Oudkerk M.Dobutamine cardiovascular magnetic resonance for the detection ofmyocardial ischemia with the use of myocardial tagging. Circulation2003;107:1592–7.

2. Wahl A, Paetsch I, Gollesch A, et al. Safety and feasibility ofhigh-dose dobutamine-atropine stress cardiovascular magnetic reso-nance for diagnosis of myocardial ischaemia: experience in 1000consecutive cases. Eur Heart J 2004;25:1230–6.

3. Korosoglou G, Lehrke S, Wochele A, et al. Strain-encoded CMR forthe detection of inducible ischemia during intermediate stress. J AmColl Cardiol Img 2010;3:361–71.

4. Paetsch I, Föll D, Kaluza A, et al. Magnetic resonance stress taggingin ischemic heart disease. Am J Physiol Heart Circ Physiol 2005;288:H2708–14.

5. Paetsch I, Jahnke C, Wahl A, et al. Comparison of dobutamine stressmagnetic resonance, adenosine stress magnetic resonance, and aden-osine stress magnetic resonance perfusion. Circulation 2004;110:835–42.

6. Schwitter J, Wacker CM, van Rossum AC, et al. MR-IMPACT:comparison of perfusion-cardiac magnetic resonance with single-photon emission computed tomography for the detection of coronaryartery disease in a multicentre, multivendor, randomized trial. EurHeart J 2008;29:480–9.

7. Gebker R, Jahnke C, Manka R, et al. High spatial resolutionmyocardial perfusion imaging during high dose dobutamine/atropinestress magnetic resonance using k-t SENSE. Int J Cardiol 2011 Feb 22[E-pub ahead of print].

8. Karamitsos TD, Leccisotti L, Arnold JR, et al. Relationship betweenregional myocardial oxygenation and perfusion in patients with coro-nary artery disease: insights from cardiovascular magnetic resonanceand positron emission tomography. Circ Cardiovasc Imaging 2010;3:32–40.

9. Rösner A, How OJ, Aarsaether E, et al. High resolution speckletracking dobutamine stress echocardiography reveals heterogeneousresponses in different myocardial layers: implication for viabilityassessments. J Am Soc Echocardiogr 2010;23:439–47.

0. Heiba SI, Yee G, Abdel-Dayem HM, Youssef I, Coppola J. Com-bined rest redistribution thallium-201 SPECT and low-dose dobut-amine contractility assessment in a simple and practical new viabilityprotocol. Ann Nucl Med 2009;23:197–203.

1. Nowak B, Schaefer WM, Koch KC, et al. Assessment of myocardialviability in dysfunctional myocardium by resting myocardial blood flowdetermined with oxygen 15 water PET. J Nucl Cardiol 2003;10:34–45.

2. Marin-Neto JA, Dilsizian V, Arrighi JA, et al. Thallium reinjectiondemonstrates viable myocardium in regions with reverse redistribution.Circulation 1993;88:1736–45.

3. Sandler MP, Patton JA. Fluorine 18-labeled fluorodeoxyglucose myo-cardial single-photon emission computed tomography: an alternativefor determining myocardial viability. J Nucl Cardiol 1996;3:342–9.

4. Duncan BH, Ahlberg AW, Levine MG, et al. Comparison ofelectrocardiographic-gated technetium-99m sestamibi single-photonemission computed tomographic imaging and rest-redistributionthallium-201 in the prediction of myocardial viability. Am J Cardiol2000;85:680–4.

5. Hanekom L, Jenkins C, Jeffries L, et al. Incremental value of strainrate analysis as an adjunct to wall-motion scoring for assessment ofmyocardial viability by dobutamine echocardiography: a follow-upstudy after revascularization. Circulation 2005;112:3892–900.

Key Words: cardiovascular magnetic resonance imaging y hibernating
myocardium y ischemia y ischemic cardiomyopathy y noninvasiveimaging.

imaging in the management of ischemic … › content › accj › 59 › 4 › 359.full.pdfimaging...

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