Herz Significance of Late Gadolinium Enhancement in Cardiovascular ...

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text for details (adapted by permission, [30]). Abbildungen 3a bis 3c. Mechanismus des LGE bei akuter und chronischer myokar- dialer Schädigung. Details s.
Herz

© Urban & Vogel 2007

Significance of Late Gadolinium Enhancement in Cardiovascular Magnetic Resonance Imaging (CMR)

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Department of Cardiology and Pulmonology, Robert Bosch Hospital, Stuttgart, Germany.

Matthias Vöhringer, Heiko Mahrholdt, Ali Yilmaz, Udo Sechtem1

Abstract Cardiovascular magnetic resonance imaging (CMR) permits optimal differentiation between normal and diseased myocardium with the use of gadoliniumbased contrast agents and special magnetic resonance pulse sequences. Imaging is performed 10–20 min after contrast agent application to produce so-called late gadolinium enhancement (LGE) images which depict diseased myocardium with excellent reproducibility. Areas showing LGE correspond to zones of myocyte necrosis or myocardial fibrosis as shown by comparison with histopathology. Typical patterns of hyperenhancement exist in ischemic heart disease

but also in dilated cardiomyopathy, hypertrophic cardiomyopathy and other inflammatory or infiltrative myocardial disease and are described in this article. LGE-CMR is helpful to distinguish advanced ischemic heart disease from nonischemic dilated cardiomyopathy. In ischemic heart disease LGE can also predict the functional recovery after revascularization procedures by directly showing the remaining viable myocardium. LGE may also become useful to predict malignant arrhythmias in patients with ischemic heart disease or nonischemic cardiomyopathy. This may lead in future to an increased role of LGE-CMR as a prognostic tool.

Key Words: Cardiac magnetic resonance · Late gadolinium enhancement · Ischemic heart disease · Dilated cardiomyopathy · Hypertrophic cardiomyopathy · Inflammatory heart disease · Infiltrative heart disease Herz 2007;32:129–37

Die Aussagekraft des Late Gadolinium Enhancement in der kardiovaskulären Magnetresonanztomographie (CMR) Zusammenfassung Mit speziellen Magnetresonanzsequenzen (s. Abbildung 2) und Gadolinium-(Gd-)basierten Kontrastmitteln kann das sog. Late Gadolinium Enhancement (LGE) dargestellt werden (s. Abbildung 1). Eine relative Anreicherung von Gd und damit ein LGE entsteht, wenn im Rahmen einer akuten Nekrose myokardiale Zellmembranen rupturiert sind und damit das Verteilungsvolumen von Gd zunimmt. Zugrunde liegen kann aber auch bei chonischen Prozessen ein im Rahmen des fibrotischen Umbaus vergrößerter extrazellulärer Raum im Myokard (s. Abbildung 3). Die verschiedenen myokardialen Erkrankungen führen zu unterschiedlicher, typischer Ausprägung von LGE (s. Abbildungen 5 bis 10). Aufgrund dieser krankheitstypischen Bilder kann LGE-CMR bei der Differentialdiagnose bei Patienten mit unklaren kardialen Krankheitsbildern, Herzinsuffizienz, Kardiomyopathien,Speichererkrankungen oder Myokarditis

Technical Aspects

The primary effect of most cardiovascular magnetic resonance imaging (CMR) contrast agents currently approved for use in humans is shortening of the longitudinal relaxation time (T1). Consequently, the goal of most CMR pulse sequences for eval-

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sehr nützlich sein. Zuverlässig kann z.B. eine fortgeschrittene ischämische Herzerkrankung von dilatativen Kardiomyopathien nichtischämischer Genese unterschieden werden. Die LGE-CMR bietet auch zunehmend Möglichkeiten zur individuellen Prognoseabschätzung. Anhand des transmuralen Ausmaßes von Infarkten lässt sich der von einer revaskularisierenden Maßnahme zu erwartende Gewinn abschätzen. Zunehmendes Interesse gilt der weiteren Charakterisierung des mit Ausmaß, Verteilung und Homogenität von LGE-Arealen (und damit von myokardialen Narben) verknüpften Risikos für das Auftreten maligner Rhythmusstörungen. Entsprechende Studien gibt es sowohl für ischämische als auch für dilatative und hypertrophe Kardiomyopathien. Eingang in die gültigen Leitlinien für entsprechende therapeutische Maßnahmen wie Implantation automatischer Kardioverter-Defibrillatoren haben diese Daten bisher noch nicht gefunden.

DOI 10.1007/ s00059-007-2972-5

Schlüsselwörter: Magnetresonanztomographie · Late Gadolinium Enhancement · Ischämische Herzkrankheit · Dilatative Kardiomyopathie · Hypertrophe Kardiomyopathie · Inflammatorische Kardiomyopathie · Infiltrative Kardiomyopathie

uation of contrast enhancement is to make image intensities a strong function of T1 (T1-weighted images). Early approaches to acquiring T1-weighted images of the heart often employed ECG-gated spin echo techniques in which one k-space line was ac-

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Same imaging session

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b T1 SE

Segmented IR GRE

Figures 1a and 1b. LGE imaging of a subendocardial myocardial infarct (arrows). Note the distinct improvement in contrast and resolution of the segmented inversion recovery gradient echo technique (IR GRE, b) compared to T1 spin echo imaging (T1 SE, a; adapted by permission, [48]). Abbildungen 1a und 1b. LGE eines subendokardialen Myokardinfarkts (Pfeile). Beachtenswert ist die deutliche Verbesserung von Kontrast und Auflösung durch die segmentierte Inversion-Recovery-Gradientenechotechnik (IR GRE, b) im Vergleich zur T1-Spinechotechnik (T1 SE, a; Nachdruck mit Erlaubnis, [48]).

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ECG

Trigger Nonselective 180° inversion α1α2 α12 1 2 12

Mz infarct α23

Nonselective 180° inversion

Mz normal

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TI Trigger 250−350 ms delay

Figure 2. Timing diagram for the segmented inversion recovery gradient echo sequence (IR GRE) with TI set to null normal myocardium after contrast agent administration (adapted by permission, [48]). Abbildung 2. Diagramm zur Veranschaulichung der segmentierten Inversion-Recovery-Gradientenechotechnik (IR GRE). TI wird so gewählt, dass normales Myokard nach Kontrastmittelgabe genullt wird (Nachdruck mit Erlaubnis, [48]).

quired in each cardiac cycle, resulting in image acquisition over several minutes during free breathing. Consequently, image quality was adversely affected by artifacts due to respiratory motion, partial volume from motional averaging over the respiratory cycle, and modest T1-weighting due to limited choices of repetition time. Since the early use of ECG-gated spin echo imaging a number of improvements have been made.

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One of the most important is the use of k-space segmentation [13], which means that multiple k-space lines are acquired during each cardiac cycle. This results in a reduction of imaging time to the point, where the entire image can be acquired during a single breath hold. In addition, the preparation of magnetization prior to image acquisition by using an inversion pulse does not only increase the degree of T1-weighting, but also nulls most signal from normal myocardium. This will result in an improvement in signal intensity ratio between enhanced and normal myocardium of up to 500% compared to most spin echo techniques (Figure 1) [48]. Figure 2 shows this optimized segmented inversion recovery gradient echo (IR GRE) sequence in more detail. Following the R-wave of the ECG a delay period (“trigger delay”) is used to ensure that acquisition of the image occurs in diastole to minimize cardiac motion. The magnetization of the heart is then prepared by a nonselective 180° inversion pulse to increase T1-weighting. The inversion delay time (TI) is defined as the time between this 180° pulse and the center of acquisition of the segmented k-space lines (lines 1–23 in Figure 2). For correct implementation, the TI must be selected manually to null signal from normal myocardium. This TI varies from patient to patient as a function of dose and time due to gadolinium contrast kinetics [29]. If applied correctly, late gadolinium enhancement (LGE) using a segmented inversion recovery gradient echo pulse sequence is highly reproducible [29, 54] and has been extensively validated in animal models and a variety of patient cohorts. This article will review the clinical significance of this technique.

Mechanisms of Late Gadolinium Enhancement (LGE)

The likely mechanism of myocardial LGE is demonstrated in Figure 3. The mechanism is based on two simple facts. First, gadolinium chelates are extracellular contrast agents that are inert and cannot cross cell membranes [40, 55]. Second, in normal myocardium, myocytes are densely packed and thus myocyte intracellular space forms the majority (~85%) of the volume [19]. Conceptually, it then follows that the volume of distribution of gadolinium in a hypothetical voxel of normal myocardium is small (Figure 3a, K indicates high potassium concentration which is typical for the intracellular milieu in a myocyte), and the overall number of gadolinium molecules (Gd) is low. In the setting of acute myocardial damage, there is myocyte membrane rupture, which allows additional gadolini-

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Vöhringer M, et al. Late Gadolinium Enhancement in CMR

um to diffuse into what was previously intracellular space (indicated by the high content in sodium [Na]). This in turn results in increased gadolinium concentration and therefore LGE (Figure 3b). In the setting of chronic myocardial damage, myocytes have been replaced with collagenous scar (symbolized by black ribbons in Figure 3c). Thus, the interstitial space is also expanded [40], which again leads to increased gadolinium concentration and therefore LGE. These mechanisms likely apply to many forms of acute and chronic myocardial damage, independent of the underlying cause (ischemia, inflammation, etc.), and may help to understand the different patterns of LGE found in different myocardial disorders [31]. However, for correct image interpretation it is important to be aware of some special situations. One is the “no-reflow phenomenon” that can be found early after acute myocardial infarction. The “no-reflow phenomenon” may be explained by intracapillary red blood cell stasis in the central necrotic region of a larger infarct that is caused by capillary plugging resulting in tissue hypoperfusion [14, 18]. Consequently, no-reflow zones will appear dark as compared to the surrounding regions of LGE due to delayed contrast penetration [30] (Figure 4). The size of the no-reflow region depends on the time between contrast injection and imaging and is larger when imaging is started early. Another special situation is diffuse plexiform fibrosis, which does not lead to detectable LGE for two reasons. First, the new optimized segmented inversion recovery sequence is sensitive to regional differences in gadolinium accumulation rather than to an overall increase of gadolinium concentration, because the technique depends on the ability to “null” signal from “remote” (presumably normal) myocardium (see Technical Aspects). Therefore, cardiac disorders that lead to focal regions of scarring will cause enhancement, whereas disorders that lead to global changes such as diffuse interstitial fibrosis will not. Second, it should be noted that the voxel resolution of LGE-CMR is approximately 1.8 mm × 1.2 mm × 6 mm. Hence, only complete scar tissue comprising several voxels will be visible on CMR images as a bright area. Regional formation of smaller scars dispersed as islands within normal myocardium which may, for instance, occur in myocarditis may result in grayish areas on LGE-CMR images. These areas may be more difficult to distinguish from normal myocardium. In summary, LGE-CMR depicts areas of necrosis or scarring in vivo that previously could only be detected at autopsy, but it is not suitable to delineate diffuse reticular interstitial fibrosis.

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Normal myocardium

a Intact cell membrane

Acute damage

b c Ruptured cell membrane

Scar

Collagen matrix

Figures 3a to 3c. Mechanism for LGE in acute and chronic myocardial damage. See text for details (adapted by permission, [30]). Abbildungen 3a bis 3c. Mechanismus des LGE bei akuter und chronischer myokardialer Schädigung. Details s. Text (Nachdruck mit Erlaubnis, [30]).

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Figures 4a to 4d. The “no-reflow” phenomenon demonstrated by LGE in repeated images, acquired at the same location over time (from left to right). The bottom labels refer to the time after contrast administration. The “no-reflow” zone often originates from the subendocardium, initially appears black surrounded by larger regions of LGE (black arrow, a), and slowly takes up contrast over time (white arrows, b to d). This can be explained by microvascular damage originating from the subendocardium (wavefront phenomenon), which impedes penetration of the contrast into this area of the infarct (adapted by permission, [30]). Abbildungen 4a bis 4d. „No-reflow“-Phänomen, dargestellt im zeitlichen Verlauf (Bezeichnungen beziehen sich auf die Zeit nach Kontrastmittelgabe). Die initial schwarz erscheinende „no-reflow“-Zone beginnt meist subendokardial und ist von größeren LGE-Regionen umgeben (schwarzer Pfeil, a). Die Kontrastierung erfolgt mit zeitlicher Verzögerung (weiße Pfeile, b bis d). Dies kann durch eine mikrovaskuläre Schädigung erklärt werden, die die Penetration von Kontrastmittel in das Zentrum des Myokardinfarkts behindert (Nachdruck mit Erlaubnis, [30]).

Significance of LGE in Ischemic Heart Disease

Animal studies invariably showed the presence of LGE in both acute and chronic myocardial infarction [14, 40]. In these studies LGE was closely correlated to histopathologic findings. LGE reflects the acute ischemic injury and only occurs in areas of irreversibly injured myocardium. The resulting scar is restricted to the supply area of the affected coronary artery. As predicted by the wavefront theory scar formation always includes the subendocardium and spreads to a variable extent from there to the epicardium [31, 41] (Figures 5 and 6). The reproducibility of

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Figures 5a to 5c. LGE in a patient with subendocardial myocardial infarction (arrows). Note the remaining viable myocardium in the epicardium. a) Typical pattern. b) Short axis. c) Long axis. Abbildungen 5a bis 5c. LGE bei einem Patienten mit einem subendokardialen Infarkt (Pfeile). Beachtenswert ist das epikardial verbliebene vitale Myokard. a) Graphik mit typischem LGE-Muster. b) Schnitt in der kurzen Achse. c) Schnitt in der langen Achse.

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Figures 6a to 6c. LGE in a patient with transmural myocardial infarction (black arrows). There is pericardial thickening overlying the infarct zone (small white arrows). a) Typical pattern. b) Short axis. c) Long axis. Abbildungen 6a bis 6c. LGE bei einem Patienten mit einem transmuralen Infarkt (schwarze Pfeile). Im Infarktgebiet besteht eine perikardiale Verdickung (kleine weiße Pfeile). a) Graphik mit typischem LGE-Muster. b) Schnitt in der kurzen Achse. c) Schnitt in der langen Achse.

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Figures 7a to 7c. LGE in a patient with dilated cardiomyopathy and a streaky midwall LGE in the septum, the so-called midwall sign (arrows). a) Typical pattern. b) Short axis. c) Long axis. Abbildungen 7a bis 7c. LGE bei einem Patienten mit dilatativer Kardiomyopathie und streifigem LGE im Septum, einem „midwall sign“ (Pfeile). a) Graphik mit typischem LGE-Muster. b) Schnitt in der kurzen Achse. c) Schnitt in der langen Achse.

LGE measurements of infarct size has proven to be excellent [29, 51]. Infarct size by LGE also correlates well with clinical findings in acute infarcts [17]. For large infarcts LGE has the same high sensitivity for infarct detection as the current gold standard single-photon emission computed tomography (SPECT)

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imaging [22]. However, due to its higher spatial resolution LGE-CMR is clearly superior to SPECT in the detection of small subendocardial infarctions (sensitivity of 92% for LGE-CMR vs. 28% for SPECT) [53]. Occasionally, it may be challenging to distinguish such small subendocardial hyperenhancements from the bright blood in the left ventricular cavity. The additional use of a short inversion time can help in this case and further improve the diagnostic accuracy of LGE-CMR [15]. LGE is also useful for detecting very small infarcts which may occur during interventional procedures [42]. Although such infarcts may not be of immediate clinical or functional relevance [4], their presence and detection may be relevant for the patients’ long-term prognosis. This was recently demonstrated in patients with small clinically unrecognized infarcts which were identified by LGE-CMR. During a median follow-up of 16 months, 31 of 195 patients (18%) experienced major adverse cardiac events (MACE), including 17 deaths. LGE demonstrated the strongest unadjusted associations with MACE and cardiac mortality. Patients in the lowest tertile of LGE-involved myocardium (mean left ventricular mass, 1.4%) still experienced a more than sevenfold increased risk for MACE. By multivariable analyses, LGE was the strongest predictor of MACE and cardiac mortality [25]. The high spatial resolution of CMR also permits detection of infarcts of the right ventricle. LGE-CMR detects right ventricular infarction more frequently than current standard diagnostic techniques [24]. LGE alone cannot distinguish between acute and chronic infarcts. This limitation may be overcome by additionally assessing myocardial edema with T2-weighted sequences or using different contrast agents [2, 45]. LGE-CMR is not only able to show the presence of irreversible myocardial damage, but it is unique in its ability of showing its transmural extent and the remaining viable myocardium. This is of high relevance to predict the prognosis after revascularization in acute myocardial infarcts [5] and to estimate the potential benefit of revascularization procedures. The transmural extent of LGE is negatively correlated to the functional outcome after revascularization [10, 20]. CMR has proven to be at least of equal accuracy as nuclear imaging in predicting the benefit of revascularization [23]. However, it needs to be pointed out that there seems to be no clear threshold of transmurality that excludes functional recovery after revascularization [32]. Therefore, outcome remains difficult to predict even by CMR when scar involves between 25% and 75% of the myocardium. Low-dobutamine stress CMR may be more reliable than LGE-CMR for prediction of recovery following revascularization

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[56] or it may improve the diagnostic accuracy of LGE when performed additionally [9]. LGE-CMR is able to detect areas within larger infarcts exhibiting the “no-reflow phenomenon” (see above) which represents a more severe form of tissue injury and is associated with a worse prognosis [59]. More recently, CMR was employed to predict susceptibility for malignant arrhythmias. Infarct surface area and mass, as measured by CMR, were better identifiers of patients who had a substrate for inducible monomorphic ventricular tachycardia than left ventricular ejection fraction [6]. When core and periinfarct regions as depicted on LGE-CMR images are separated using a computer-assisted, semiautomatic algorithm based on signal-intensity thresholds (core > 3 SDs [standard deviations] and periphery 2–3 SDs above remote normal myocardium), patients with an above-median % LGE periphery are at a significantly higher risk for death compared with those with a below-median % LGE periphery [60]. This indicates that the extent of the periinfarct zone as characterized by CMR may provide incremental prognostic value beyond left ventricular systolic volume index or ejection fraction. It is hypothesized that the so estimated “patchiness” of infarcts may be the substrate for electric reentry mechanisms. Infarct characteristics as assessed by CMR may thus prove to become unique and valuable noninvasive predictors of post-myocardial infarction mortality. Another potential application of LGE-CMR is to plan and predict the outcome of cardiac resynchronization therapy (CRT) by the distribution and the amount of scar. CRT does not reduce left ventricular dyssynchrony in patients with transmural scar tissue in the posterolateral left ventricular segments diagnosed by LGE-CMR, resulting in clinical and echocardiographic nonresponse to CRT [7]. Moreover, percent total scar is significantly higher in the nonresponse versus response group and predicts a lack of response by receiver-operating characteristic analysis [57].

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LGE may also occur in nonischemic cardiac diseases such as dilated cardiomyopathy or hypertrophic cardiomyopathy. Dilated cardiomyopathy (DCM) is defined as dilation and impairment of function of one or both ventricles. DCM may be genetically determined or may be caused by chronic myocarditis, toxic agents, muscle dystrophies or neuromuscular diseases, metabolic and storage diseases, or systemic inflammatory diseases. It is important to differentiate between advanced diffuse ischemic heart disease and DCM be-

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Figures 8a to 8c. LGE in a patient with hypertrophic cardiomyopathy. Note the patchy LGE at the junction of the right ventricle and the interventricular septum (arrows). a) Typical pattern. b) Short axis. c) Long axis. Abbildungen 8a bis 8c. LGE bei einem Patienten mit hypertropher Kardiomyopathie. Beachtenswert ist das LGE an den Insertionsstellen des rechten Ventrikels (Pfeile). a) Graphik mit typischem LGE-Muster. b) Schnitt in der kurzen Achse. c) Schnitt in der langen Achse.

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Figures 9a to 9c. LGE in a patient with acute myocarditis proven by endomyocardial biopsy. Note the epicardial LGE in the inferolateral wall (arrows). a) Typical pattern. b) Short axis. c) Long axis. Abbildungen 9a bis 9c. LGE bei einem Patienten mit akuter Myokarditis, die durch Myokardbiopsie bestätigt wurde. Beachtenswert ist das epikardiale LGE (Pfeile). a) Graphik mit typischem LGE-Muster. b) Schnitt in der kurzen Achse. c) Schnitt in der langen Achse.

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Significance of LGE in Nonischemic Cardiomyopathies

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Figures 10a to 10c. LGE obtained early (5 min) after contrast application in a patient with cardiac amyloidosis proven by endomyocardial biopsy (arrows). a) Typical pattern. b) Short axis. c) Long axis. Abbildungen 10a bis 10c. LGE bei einem Patienten mit histologisch nachgewiesener kardialer Amyloidose, das sich früh nach Kontrastmittelgabe (5 min) darstellt (Pfeile). a) Graphik mit typischem LGE-Muster. b) Schnitt in der kurzen Achse. c) Schnitt in der langen Achse.

cause different therapeutic options exist. The typical subendocardial or transmural LGE in a coronary supply area is indicative of ischemic heart disease [33, 50, 58]. In the presence of heart failure and obstructive coronary heart disease this pattern of LGE occurs in virtually all patients. However, ischemic pat-

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terns of scar may also be observed in 10–15% of patients with diffuse global reduction of left ventricular function felt to have DCM as they do not have obstructive coronary disease but only diffuse plaque formation within the coronary arteries [33, 43, 50]. This ischemic pattern of scar without corresponding obstruction in the supplying coronary artery might be caused by transient occlusion by a thrombus or embolus or coronary vasospasm occurring in addition to the underlying myocardial abnormality. In these patients, the extent of subendocardial scar does not explain the extent of wall motion abnormalities. Two other patterns of LGE are more frequent in patients with DCM: no LGE and a streaky or patchy enhancement in the midwall of the left ventricle [33] (Figure 7). Midwall LGE has an adverse prognosis as compared to DCM without LGE [3]. The histological basis for LGE is replacement fibrosis which is found at necropsy in approximately half of the patients dying of the disease [43]. Recently, the midwall LGE pattern was found to be associated with active or borderline myocarditis by Dallas criteria in patients with a clinical presentation of chronic myocarditis and depressed left ventricular function or repetitive ventricular arrhythmias. This indicates that LGE-CMR may be able to identify the cause of ventricular dysfunction in a subset of patients with DCM [12]. As LGE is predictive of an adverse prognosis in patients with DCM, a potential clinical application is to provide such patients with an antiarrhythmic device. Such a strategy in DCM is supported by the finding that DCM patients with predominance of scar distribution involving 26–75% of wall thickness are more prone to have inducible ventricular tachycardia. LGE-CMR may hence identify high-risk patients with nonischemic cardiomyopathy currently missed by ejection fraction criteria [38]. In patients with hypertrophic cardiomyopathy (HCM), LGE is a frequent finding [11, 34]. Hyperenhancement is the result of a number of pathologic processes that result in different forms of fibrosis (replacement scar or myocyte dropout) or in relation to myocardial disarray and subsequent local interstitial expansion. The different patterns of hyperenhancement are likely to be linked to the different pathologic processes occurring in different patients, and the different stages that such processes have reached at the time of scanning. In a histopathologic comparative study in a patient who underwent heart transplantation shortly after CMR imaging, there was excellent correlation of LGE and fibrosis [35]. LGE appears most frequently at the junctions of interventricular septum and the right ventricle (Figure 8). Other typical locations are the most hypertrophied areas which are usually located in the septum. LGE

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occurs in a multifocal, patchy pattern. In advanced stages of the disease there is progressive scarring which may finally lead to wall thinning [34]. The total amount of scar correlates with the clinical risk factors currently used to estimate the patient’s need for an antiarrhythmic device [34]. However, it has yet to be shown convincingly that LGE-CMR can provide additional or better information for risk assessment in HCM.

Significance of LGE in Inflammatory Heart Disease

The most common cause of inflammatory heart disease in Europe is acute viral myocarditis. The histological substrate for LGE in acute myocarditis is myocyte necrosis and not replacement fibrosis as in chronic myocarditis. LGE therefore represents the severity and focality of inflammation, which is determined by the patient’s disposition and the infectious viral agent. Differences in patient population, clinical or biopsy inclusion criteria are the likely explanation of the varying incidence of LGE observed in acute myocarditis ranging from 44% to 88% [1, 27]. The distribution of LGE is typically patchy in the epicardium of the inferolateral wall or more band-like in the midwall of the septum (Figure 9). The patterns of LGE may be related to the type of virus or viruses causing the inflammation [28]. The specificity of LGE in acute myocarditis is very high up to 100% [49]. In selected patients, the sensitivity of endomyocardial biopsy is improved if biopsies can be obtained from the region of LGE as compared to nonenhancing regions [27]. Epicardial LGE in acute myocarditis decreases with healing of myocarditis [31] which may be explained by the patchy nature of the inflammation. With shrinkage of the small scattered scars which are still surrounded by normal myocytes, expansion of the extracellular space per voxel may become so small that enhancement becomes invisible. Another possibility is that there is some expansion of the interstitium by edema which may be prominent in the acute stage but disappears with healing [16]. Inflammation in the myocardium is also part of the clinical spectrum in patients with Chagas’ disease. LGE is frequently found in these patients and sometimes even before clinical manifestation of the disease [44]. The pattern of LGE is similar to that in acute viral myocarditis [8]. It also affects predominantly the epi- and midventricular layer of the inferolateral wall. The amount of LGE seems to be correlated with the severity of ventricular dysfunction and severe arrhythmias [44]. In sarcoidosis cardiac involvement is difficult to diagnose clinically but present in 20–30% of patients

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in autopsy studies [47]. LGE typically occurs in cardiac sarcoidosis as areas of focal, patchy hyperenhancement usually located subepicardial or in the midwall [21, 52]. In a study with examination of consecutive patients with biopsy-proven pulmonary sarcoidosis, LGE has emerged as an excellent tool to detect cardiac involvement [46].

Significance of LGE in Infiltrative Heart Disease

Cardiac amyloidosis is characterized by deposition of amyloid in the interstitium causing expansion of the interstitial space. This allows gadolinium-based MR contrast agents to diffuse into the interstitium and leads to LGE despite the absence of larger amounts of necrosis or fibrosis. The hyperenhancement is diffuse throughout the ventricle but pronounced in the subendocardium (Figure 10). It is best demonstrated early after contrast injection. Therefore, imaging should be started already 5 min after contrast injection. If this is respected, LGE has an excellent diagnostic accuracy of 97% [26]. It can be expected that LGE should be able to demonstrate regression of amyloid with treatment, but this has not yet been reported. Another storage disease with cardiac involvement is Anderson-Fabry disease. It leads to diffuse cardiac hypertrophy due to intramyocardial accumulation of sphingolipids. Although this is a diffuse process throughout the myocardium, patients with more severe disease may show focal inferolateral midwall LGE [36]. LGE is caused by fibrosis as shown by correlation with autopsy findings [37], but it remains unknown why fibrosis appears focal and predominantly in the inferolateral wall.

Conclusion

LGE is usually not performed on its own but is part in a CMR examination protocol providing comprehensive information in patients with heart disease [39]. In such a protocol LGE is a powerful tool to determine the presence and extent of myocardial diseases and can help the clinician to identify the etiology of heart-related symptoms and heart failure. However, the specificity of LGE for differentiating between the various forms of nonischemic myocardial disease appears to be rather low indicating that endomyocardial biopsy cannot be replaced by CMR. There is increasing evidence that the total amount and the pattern of distribution of LGE are of prognostic value especially with respect to its potential ability to predict malignant arrhythmias. This may lead to an expanding prognostic role of LGE-CMR.

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Conflict of interest: None. The authors declare that they had no financial or personal relations to other parties whose interests could have affected the content of this article in any way, either positively or negatively.

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Address for Correspondence Udo Sechtem, MD Abteilung für Kardiologie und Pulmologie Robert-Bosch-Krankenhaus Auerbachstraße 110 70376 Stuttgart Germany Phone/Fax (+49/711) 8101-3456 e-mail: [email protected]

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