Download Herz Significance of Late Gadolinium Enhancement in

Herz
© Urban & Vogel 2007
Significance of Late Gadolinium
Enhancement in Cardiovascular
Magnetic Resonance Imaging (CMR)
1
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-
Herz 32 · 2007 · Nr. 2 © Urban & Vogel
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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Vöhringer M, et al. Late Gadolinium Enhancement in CMR
Same imaging session
a
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]).
R
R
R
ECG
Trigger
Nonselective
180° inversion
α1α2 α12
1 2 12
Mz infarct
α23
Nonselective
180° inversion
Mz normal
23
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.
130
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-
Herz 32 · 2007 · Nr. 2 © Urban & Vogel
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.
Herz 32 · 2007 · Nr. 2 © Urban & Vogel
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]).
a
b
c
d
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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Vöhringer M, et al. Late Gadolinium Enhancement in CMR
a
b
c
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.
a
b
c
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.
a
b
c
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)
132
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
Herz 32 · 2007 · Nr. 2 © Urban & Vogel
Vöhringer M, et al. Late Gadolinium Enhancement in CMR
[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].
a
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-
Herz 32 · 2007 · Nr. 2 © Urban & Vogel
c
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.
a
b
c
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.
a
Significance of LGE in Nonischemic
Cardiomyopathies
b
b
c
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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Vöhringer M, et al. Late Gadolinium Enhancement in CMR
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
134
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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Vöhringer M, et al. Late Gadolinium Enhancement in CMR
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.
Herz 32 · 2007 · Nr. 2 © Urban & Vogel
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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