Mri in Myocardial Disease
Content
1520
REVIEW
Cardiac magnetic resonance in myocardial disease
Udo Sechtem, Heiko Mahrholdt, Holger Vogelsberg
...................................................................................................................................
Heart 2007;93:1520–1527. doi: 10.1136/hrt.2005.067355
For a number of patients it is difficult to diagnose the cause of
cardiac disease. In such patients cardiac magnetic resonance is
useful for helping to make a differential diagnosis between
ischaemic and dilated cardiomyopathy; identifying patients with
myocarditis; diagnosing cardiac involvement in sarcoidosis and
Chagas’ disease; identifying patients with unusual forms of
hypertrophic cardiomyopathy and those with continuing
myocardial damage; and defining the sequelae of ablation
treatment for hypertrophic obstructive cardiomyopathy.
.............................................................................
P
atients presenting with cardiac disease usually
become aware of their health problem by
recognising one of three types of symptoms:
signs of heart failure, chest discomfort or arrhythmias. Another group of patients may require more
detailed investigation owing to asymptomatic ECG
changes which appeared during a routine medical
check-up. Patients presenting with heart-related
problems usually undergo an exercise stress test
and transthoracic echocardiography. The results of
these tests in combination with a careful history
will distinguish between those with coronary
artery disease, valvular heart disease, cardiomyopathies or other less common variants of cardiac
problems. However, in a subgroup of patients it is
difficult to identify the cause of the problem even
after cardiac catheterisation and those patients
often have conditions where cardiac function is
impaired, but this impairment cannot be explained
by coronary artery disease or abnormal loading
conditions. It is in these patients where cardiac
magnetic resonance (CMR) will be clinically helpful to characterise further the pathophysiology
underlying the patient’s problem and help to make
a diagnosis.
DILATED CARDIOMYOPATHY (DCM) AND
CHRONIC VIRAL MYOCARDITIS
See end of article for
authors’ affiliations
........................
Correspondence to:
Professor Dr U Sechtem,
Division of Cardiology and
Pulmology, Robert-BoschKrankenhaus,
Auerbachstrasse 110,
D-70376 Stuttgart,
Germany; udo.sechtem@
rbk.de
Accepted 21 May 2006
Published Online First
6 June 2006
........................
www.heartjnl.com
In patients with symptoms and signs of heart
failure of recent onset, echocardiography often
discloses an enlarged, poorly contractile left
ventricle (LV) and sometimes also signs of right
ventricular dysfunction. As the patients often also
report chest pain the differential diagnosis of the
cause of heart failure is broad. The challenge is to
distinguish between ischaemia, infection, inflammation or ‘‘idiopathic’’ disease. In patients without
a typical history of coronary artery disease with
myocardial infarction an ischaemic cause of
ventricular dysfunction is still commonly ruled
out by routine coronary angiography. The assumption is that the finding of stenosed or occluded
coronary arteries is synonymous with the presence
of ischaemic scar or hibernation. A perfect
demonstration of an ischaemic cause of heart
failure requires demonstration of an ischaemic
scar or hibernation, in addition to depicting
coronary morphology by coronary angiography or
computed tomography.1 Perfusion defects shown
by nuclear myocardial perfusion imaging usually
indicate an ischaemic scar, but such defects can
also by found in patients with DCM. Segmental
wall motion abnormalities are the mainstay of the
echocardiographic differentiation, but they may
not always distinguish between the two entities.2
Myocardial tissue differentiation by echocardiography is still in its infancy and relies on indirect
signs such as differences in strain rate.3
Late gadolinium enhancement (LGE) is a new
tool provided by CMR.4 LGE depicts areas of
myocardial necrosis and fibrosis with high spatial
resolution and accurately reflects ‘‘true’’ changes
demonstrated by pathology both in animal models4
and human disease.5 When appropriate pulse
sequences optimised to reflect differences in the
spin–spin relaxation time T2 are used, CMR may
also be able to depict tissue oedema.6 Oedema
often accompanies inflammatory myocardial disease.7
How can CMR be used for distinguishing
between patients with ischaemic and non-ischaemic heart failure? Ischaemic scar is either subendocardial or transmural.8 CMR is sensitive in
detecting even small amounts of subendocardial
infarction.9 Thus it is also sensitive in detecting
ischaemic heart failure as some degree of scar will
usually be present in ischaemically injured, poorly
contractile ventricles. On the other hand, subendocardial enhancement should be absent in
patients with normal coronary arteries and left
ventricular dysfunction. Indeed, several groups
have now confirmed that LGE-CMR finds scar
tissue in almost all patients with a previously
identified infarct related artery but only rarely in
patients with non-ischaemic cardiomyopathy or
healthy volunteers (table 1).10–12 Peculiar findings
seen in patients without coronary artery disease
are longitudinal striae of mid-wall enhancement,
clearly different from the subendocardial or
transmural enhancement pattern seen in patients
with coronary artery disease (fig 1).
Recently, the mid-wall LGE pattern was found
to be associated with active or borderline myocarditis by Dallas criteria13 in patients with a clinical
presentation of chronic myocarditis and depressed
left ventricular function or repetitive ventricular
Abbreviations: CMR, cardiac magnetic resonance; DCM,
dilated cardiomyopathy; EMB, endomyocardial biopsy;
HCM, hypertrophic cardiomyopathy; LGE, late gadolinium
enhancement; LV, left ventricle; PVB19, parvovirus B19
Cardiac magnetic resonance in myocardial disease
1521
Table 1 CMR distinguishes between ischaemic and non-ischaemic cardiomyopathy
Reference
n
Wu et al10
71
11
McCrohon et al 90
12
71
Soriano et al
Inclusion criteria
Proven MI or dilated cardiomyopathy
Clinical heart failure, coronary angiography
Clinical heart failure, systolic LV dysfunction,
no CAD history, no previous MI, no Q-waves
LVEF
(%)
CAD Subendo LGE
(n)
No (%)
Mid-wall LGE No CAD
No (%)
(n)
Subendo LGE
No (%)
Mid-wall LGE
No (%)
NA
33–39
51
27
48 (94)
27 (100)
0 (0)
0 (0)
20
63
0 (0)
8 (13)
0 (0)
18 (28)
27
26
21 (81)
96/104 (92)
3 (11)
3/104 (3)
45
4 (9)
12/128 (9)
4 (9)
22/128 (17)
Total
CAD, coronary artery disease; LVEF, left ventricular ejection fraction; MI, myocardial infarction; Subendo, subendothelial.
arrhythmias.14 This pattern was seen just as often in patients
with active myocarditis (43%) as in those with borderline
myocarditis (44%). Interestingly, patients with a clinical
diagnosis of dilated cardiomyopathy and mid-wall LGE have
a worse prognosis, as measured by unplanned admission to
hospital or death, than patients with a similar degree of left
ventricular dysfunction but no mid-wall LGE (Prasad S,
unpublished data).
What is the histological basis of such non-endocardial
myocardial enhancement in patients with DCM which does
not correspond to the perfusion bed of a coronary artery?
Although inflammation seems to play a part with such
intramyocardial or epicardial changes,14 inflammation is unlikely to be the sole cause of LGE. As in LGE associated with
infarction, an important mechanism of enhancement is the
expansion of extracellular space associated with myocardial
necrosis14 and later fibrosis.15 Myocyte necrosis is a feature of
acute myocarditis as defined by the Dallas criteria, and
myocardial fibrosis is usually found at postmortem examinations in patients with a diagnosis of DCM. Myocyte necrosis in
myocarditis is usually disseminated, but larger confluent areas
may exist.16 Fibrotic changes may also be diffuse or more
patchy. The LGE technique is unlikely to detect diffuse necrotic
or fibrotic changes as it is designed to optimise contrast
between normal and necrotic myocardium in patients with
focal ischaemic necrosis.17 Hence, no enhancement will be seen
by LGE-CMR in patients with diffuse myocardial damage. In
contrast, LGE-CMR does have sufficient spatial resolution to
resolve small foci of myocardial necrosis or fibrosis in vivo.18 It
is currently unknown whether the amount of fibrosis seen by
CMR has prognostic value.
ACUTE VIRAL MYOCARDITIS
Clinical symptoms in patients with acute myocarditis may be
absent and the only clue to the presence of the disease may be
changes in the ECG. At the other end of the spectrum, patients
may come to the hospital in cardiogenic shock. As myocarditis
Patient A
Patient B
may be associated with systemic viral illness, patients may
report tiredness, muscle aches, chest pain and palpitations.
There are three more dramatic modes of presentation associated
with myocarditis. First, myocarditis may manifest as acute
onset of heart failure in a previously healthy person. Second, it
may masquerade as an acute coronary syndrome. Third,
arrhythmias including ventricular tachycardia may be the
leading symptom, sometimes manifesting as sudden cardiac
death. Establishing the diagnosis of myocarditis is difficult as
there are currently no non-invasive tools to verify the diagnosis
and assess the extent of myocardial involvement. The ultimate
proof that the patient has myocarditis is provided by
endomyocardial biopsy (EMB), which may demonstrate the
typical inflammatory infiltrate in the myocardium. Using
molecular hybridisation or PCR methods, it is possible to
identify the causative viral agent. However, myocarditis is a
patchy disease, which may explain the sampling error limiting
the diagnostic value of endomyocardial biopsy.19
Friedrich et al were the first to propose CMR for non-invasive
diagnosis of clinically acute myocarditis.20 They observed that
the myocardium in patients with the clinical manifestations of
myocarditis showed hyperenhancement relative to skeletal
muscle on T1-weighted images. However, the imaging protocol
used in that study yielded a low contrast between inflamed and
normal myocardium and suffered from image artefacts.
New contrast-enhanced CMR techniques such as the one
employed for infarct imaging17 provide an improvement in
contrast between diseased and normal myocardium of up to
500% when compared with the protocol used by Friedrich et al.
When these new inversion recovery gradient echo techniques
are used in patients with clinically suspected myocarditis
(history of respiratory or gastrointestinal symptoms with
8 weeks of admission in combination with fatigue/malaise,
chest pain, dyspnoea or tachycardia plus ECG changes such as
conduction block, ST abnormalities, supraventricular tachyarrhythmia or ventricular tachycardia) LGE is found in up to 90%
of the patients.21 The regions of LGE have a patchy distribution
Figure 1 Short-axis images in two patients
presenting with heart failure, enlarged left
ventricle and systolic dysfunction. The
corresponding contrast cardiac magnetic
resonance images demonstrate nearly
transmural late gadolinium enhancement
(LGE) in the anteroseptal wall consistent with
a prior myocardial infarction in the patient
with ischaemic heart disease (patient A),
whereas typical mid-wall stria-type LGE is
present in the patient with non-ischaemic
cardiomyopathy (patient B).
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1522
Sechtem, Mahrholdt, Vogelsberg
Figure 2 Left and middle panel: basal and
mid-ventricular short-axis late gadolinium
enhancement-cardiac magnetic resonance
image in a 26-year-old man with the clinical
picture of acute myocarditis demonstrating
epicardial enhancement in the posterolateral
aspects of the left ventricle (arrows). The
three-chamber view (right panel) shows
prominent bright foci of enhancement in the
lateral wall (arrows). Biopsy disclosed
parvovirus B19 infection.
throughout the LV. They are frequently located in the lateral
free wall (fig 2) and originate from the epicardial quartile of
that wall. Another commonly seen pattern is the mid-wall stria
pattern in the basal interventricular septum mentioned above
in patients with chronic myocarditis.
Biopsy specimens obtained from the area of LGE show acute
or borderline myocarditis13 in a higher percentage than reported
in the literature.22 However, one has to consider that an increase
in the number of activated macrophages (.14/high power
field) was an additional criterion for making the diagnosis of
borderline myocarditis in the study by Mahrholdt et al.21 This
represents an extension of the original Dallas criteria,13 and an
increased sensitivity of EMB can hence be expected.
Irrespective of this point, myocarditis is seen less consistently
in patients in whom the biopsy cannot be obtained from the
region of contrast enhancement (found in only one of seven
patients in the study by Mahrholdt et al21). Thus, CMR-guided
biopsy in the right or the left ventricle may result in a higher
yield of positive findings than routine right ventricular biopsy.23
As mentioned above, the inability to demonstrate diffuse
myocardial changes as encountered in diffuse myocarditis with
diffuse oedema formation is a disadvantage of the LGE
technique. Even localised oedema without accompanying
myocyte death might not result in sufficient increase in
T1/pre contrast
T2
Late post contrast
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T1/early post contrast
extracellular space to cause LGE. Thus, the sensitivity of LGE
to detect milder forms of myocarditis may be suboptimal.
Recently, it has been suggested that CMR imaging optimised at
detecting inflammation or oedema may be more sensitive for
identifying patients with acute myocarditis.24 Three different
pulse sequences were compared in patients with cardiac
symptoms such as angina, dyspnoea or palpitations accompanied by ECG changes such as ST-segment changes or
conduction defects and raised serum markers. A T2-weighted
triple inversion recovery pulse sequence showed a significantly
higher global myocardial signal intensity in patients than in
volunteers, although there was overlap. A cut-off value of 1.9
had a sensitivity of 84% and a specificity of 74% to identify the
disease. A T1-weighted spin echo before and shortly after
contrast injection (as described by Friedrich et al20) yielded a
significantly higher global myocardial relative enhancement in
patients than in volunteers. A cut-off value of 4.0 had a
sensitivity of 80% and a specificity of 73% to identify
myocarditis. The sensitivity of a inversion recovery gradient
echo pulse sequence (LGE sequence) started 10 minutes after
contrast injection was lower at only 44% (fig 3), but the
specificity was high (100%). The best diagnostic performance
was obtained when any two of the criteria obtained by the three
techniques were positive in a given patient.24 One needs to
Figure 3 Cardiovascular magnetic
resonance findings in a patient with acute
chest pain and ST elevations in II, III, aVF as
well as negative T-waves in II, III, aVF, V5–
V6. The patient also had a mild increase of
cardiac markers. (Top) Pre- and postcontrast
axial T1-weighted spin-echo images of the
same slice. Global relative enhancement was
increased (4.1). (Middle) T2-weighted
images in three short-axis slices. Note the
posterolateral focal high T2 signal
(arrowheads) in the basal slice with apparent
focal increase in myocardial thickness.
(Bottom) Corresponding late enhancement
images: no evidence of late gadolinium
enhancement. Reprinted with permission
from Abdel-Aty H, Boye´ P, Zagrosek A, et al.
The sensitivity and specificity of
contrastenhanced and T2-weighted
cardiovascular magnetic resonance to detect
acute myocarditis. J Am Coll Cardiol
2005;45:1815–22.24
Cardiac magnetic resonance in myocardial disease
ACUTE
1523
Figure 4 Serial late gadolinium
enhancement (LGE) images in another
patient with acute parvovirus B19
myocarditis. Upper panel: short-axis (left)
and four-chamber view (right) images show
prominent enhancement of the lateral wall
extending almost throughout the entire wall
but originating from the epicardium
(arrows). Lower panel: at follow-up LGEcardiac magnetic resonance 4 months later,
the inflammatory lesions have faded and
become smaller. Reprinted with permission
from Mahrholdt H, Goedecke C, Wagner A,
et al. Cardiovascular magnetic resonance
assessment of human myocarditis: a
comparison to histology and molecular
pathology. Circulation 2004;109:1250–8.21
FU (12 weeks)
remember, however, that in this series the preferred method for
identifying myocarditis was the clinical presentation of the
patient, and EMB was not performed.
CMR is also helpful for differentiating between acute injury
due to inflammation and ischaemic injury.25 Whereas patients
with acute myocardial infarction show segmental early
subendocardial defects on perfusion MRI, with corresponding
segmental subendocardial or transmural LGE in a vascular
distribution, patients with myocarditis have no early defect and
focal or diffuse non-segmental non-subendocardial LGE.
Moreover, CMR gives first insights into the clinical course of
patients with myocarditis. It appears that T1 contrast enhancement decreases to almost normal values within 4 weeks after
the initial clinical presentation in most patients.26 The area of
LGE also decreases in many patients and enhancement may
disappear completely (fig 4). However, the decrease in
enhancement is only moderately correlated with the improvement in ejection fraction.21
In Germany, PVB19 is currently the most commonly
encountered causative agent, followed by adenovirus and
human herpes virus type 6.21 27 Parvovirus associated myocarditis often shows LGE of the epicardial portions of the free
lateral wall of the LV.28 Interestingly, epicardial lesions are also
the predominant findings in canine parvovirus myocarditis.29
This finding may, however, not be parvovirus specific as in the
United States gross lesions have also been found in epicardial
portions of the posterolateral free wall in patients dying
suddenly with acute myocarditis,30 although parvovirus
Figure 5 Spin-echo (upper panel) and late
gadolinium enhancement-cardiac magnetic
resonance (LGE-CMR; lower panel) images
in a patient with biopsy proven with
pulmonary sarcoidosis. A diffuse signal is
seen in both lungs on spin-echo images. LGE
short-axis images (three images from the left
in the lower panel from base to apex)
demonstrate inferior and lateral
enhancement not dissimilar to that seen in
myocarditis. With steroid treatment,
symptoms improved and myocardial
enhancement became fainter.
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1524
Sechtem, Mahrholdt, Vogelsberg
Figure 6 Patient with asymmetric
hypertrophy and small scars at junctions
between the left and right ventricles (arrows)
shown by late gadolinium enhancementcardiac magnetic resonance. Left: short-axis
image. Right: two-chamber view parallel to
the interventricular septum.
infection is not common in the United States.31 In contrast, the
peculiar pattern of a sandwiched stripe of late enhancement
within the interventricular septum is more frequently found in
herpes virus or mixed infections caused by herpes virus and
parvovirus.28 Intraseptal lesions are also seen at necropsy in
patients dying of active myocarditis.19
OTHER FORMS OF INFLAMMATORY
CARDIOMYOPATHY
In patients with clinical signs of cardiac sarcoidosis (arrhythmias, conduction disturbances, heart block, pericardial effusion
or sudden death), cine CMR usually demonstrates regional wall
motion abnormalities and may also show wall thickening of the
affected region.32 T2-weighted imaging may demonstrate
diffuse regional signal increase. LGE often shows focal areas
of inflammation or fibrosis, or both,33 (fig 5) and contrast
enhancement may show patterns of epicardial enhancement
similar to that seen in myocarditis. As in patients with
myocarditis, findings of T2 and LGE images are not necessarily
concordant. Although CMR findings may be non-specific, the
high sensitivity makes CMR an attractive first-line non-invasive
method for early diagnosis and follow-up of cardiac sarcoidosis.
Chagas’ disease is an inflammatory form of myocardial
disease caused by the protozoan Trypanosoma cruzi. Although
the inflammatory myocardial process is crucial for parasite
control, inflammation may become progressive, resulting in
chronic disease that is characterised by myocarditis associated
with prominent fibrosis and cardiac dysfunction. CMR demonstrates myocardial LGE in two-thirds of patients diagnosed
with Chagas’ disease,34 and the incidence increases with
increasing severity of cardiac dysfunction and is most pronounced in patients with severe ventricular arrhythmias. LGE
patterns may be similar to viral myocarditis, affecting the
epicardial portion of the LV free wall.34 Thus, CMR enables the
quantification of myocardial inflammation and fibrosis in
Chagas’ disease, adding important information on disease
severity, and may become useful for early identification of
cardiac involvement in the subclinical phases of the disease
process.
HYPERTROPHIC CARDIOMYOPATHY
CMR has also become a useful technique in the management of
patients
with
hypertrophic
cardiomyopathy
(HCM).
Differentiating between HCM and other forms of hypertrophy
has remained a substantial challenge for imaging techniques.
Although most patients with HCM have a typical asymmetric
pattern of hypertrophy affecting the interventricular septum
more than the posterolateral wall, concentric, apical and other
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atypical distributions of hypertrophy do exist. These atypical
forms of hypertrophy, in particular, may be difficult to
recognise by echocardiography. CMR can identify such regions
of LV hypertrophy and thus represents a powerful supplemental
imaging test with distinct diagnostic advantages for selected
patients with HCM.35 36
CMR can also be used to assess myocardial tissue characteristics in vivo by applying the late enhancement technique to
patients with HCM. Myocardial scarring is a common finding in
patients with HCM and may be prognostically important.
Scarring occurs mostly in hypertrophied regions and is usually
patchy with multiple foci, predominantly affecting the midventricular wall.37 However, the location of scarring does not
correspond to the perfusion territories of the epicardial
coronary arteries. It is currently not clear whether increased
numbers of structurally abnormal intramural coronary arteries
within areas of scarred myocardium have a causal role in
producing myocardial ischaemia leading to scarring. In patients
with small areas of scarring, the junctions of the interventricular septum and the right ventricular walls are commonly
affected (fig 6). In patients with disease caused by mutations in
the troponin I gene, focal fibrosis is usually not detected by
LGE-CMR before left ventricular hypertrophy and ECG
abnormalities are present.38 However, once hypertrophy is
present, LGE is common and the extent correlates with adverse
clinical measures. This suggests that focal fibrosis is closely
linked to disease development. The extent of scarring measured
by CMR correlates with conventional risk markers, but it is
currently not clear whether the extent of scarring in the CMR
will be more predictive of serious arrhythmic events than the
current risk stratification based on risk factors.
Patients with severe forms of hypertrophic cardiomyopathy
may develop progressive left ventricular impairment associated
with progressive interstitial fibrosis, myocardial disarray, small
vessel disease, and microscopic scarring leading to wall
thinning. CMR demonstrates a greater extent of hyperenhancement in patients with clinically progressive disease and this is
associated with thinning of previously grossly hypertrophied
myocardium.39
Similar to (colour) Doppler echocardiography, CMR can depict
and quantify the turbulent jet in the left ventricular outflow tract
in patients with the obstructive form of HCM. A unique advantage
of CMR is the opportunity for monitoring and quantifying the
changes induced by septal ablation of the obstructive lesion (fig 7).
The remodelling of the left ventricular outflow tract can be serially
monitored during the healing process.40
Thus, CMR provides comprehensive information on anatomy,
function and tissue composition in patients with HCM.
Cardiac magnetic resonance in myocardial disease
A
B
C
D
Although the value of CMR as compared with echocardiography is not clearly defined yet, CMR will be useful in patients for
whom complete information cannot be obtained by echocardiography.
OTHER CARDIOMYOPATHIES
Stress-induced cardiomyopathy
Left apical ballooning (takotsubo cardiomyopathy) is a clinical
entity characterised by acute but rapidly reversible left
1525
Figure 7 Contrast-enhanced images
20 minutes after intravascular administration
of gadolinium-DTPA in two patients with
hypertrophic obstructive cardiomyopathy
1 month after percutaneous transluminal
septal myocardial ablation. (A, B) Threechamber view and short-axis view in a
patient with transmural septal infarction.
(C, D) Comparable views in a patient with
myocardial infarction located exclusively on
the right ventricular side of the
interventricular septum. Reprinted with
permission from van Dockum WG, ten Cate
FJ, ten Berg JM, et al. Myocardial infarction
after percutaneous transluminal septal
myocardial ablation in hypertrophic
obstructive cardiomyopathy: evaluation by
contrast-enhanced magnetic resonance
imaging. J Am Coll Cardiol 2004;43:27–
34.40
ventricular systolic dysfunction in the absence of atherosclerotic coronary artery disease, often triggered by profound
psychological stress. Catecholamine production and myocardial
stunning are thought to be involved pathophysiologically and
the distal portion of the LV is most commonly affected. CMR
contributes to an understanding of this new entity by
demonstrating the absence of irreversible injury41 (LGE) but
oedema formation on T2-weighted images. CMR also aids in
clearly identifying segmental wall-motion abnormalities
Figure 8 Subendocardial enhancement on late gadolinium enhancement short-axis (left from base to apex) and two-chamber view (parallel to
interventricular septum) images in a patient with immunoglobulin light chain (AL) cardiac amyloidosis due to multiple myeloma. Note that image acquisition
needs to be started earlier than the usual 10 minutes after contrast injection as the contrast agents quickly diffuse into the amyloid-filled enlarged interstitial
space, and differential enhancement may be absent at later phases of the diffusion process. In patients with possible amyloid disease (eg, in all patients with
unexplained left ventricular hypertrophy) and abnormal findings on TI scout images, an early series of contrast images should be acquired.
www.heartjnl.com
1526
encompassing the left ventricular myocardium in multiple
coronary arterial vascular territories.42 In patients with severe
haemodynamic impairment, CMR may also demonstrate
involvement of the right ventricle.
Infiltrative cardiomyopathies
Cardiac involvement is common in systemic amyloidosis. It is a
major determinant of treatment options and prognosis and is a
frequent cause of death. Myocardial disease is often the only
manifestation of transthyretin amyloidosis. Storage of proteins
in the insoluble fibrillar amyloid conformation occurs principally in the myocardial interstitium, with a preference for the
subendocardial space. Clinically, patients present with signs of
diastolic heart failure progressing to restrictive cardiomyopathy.
Relaxation time T1 measured from T1 maps is significantly
lower in the subendocardial space of patients with amyloidosis
than in hypertensive controls. Moreover, within patients,
subendocardial T1 is lower than T1 in the subepicardium for
the first 8 minutes after the administration of a gadoliniumbased contrast agent.43 This difference is no longer apparent at
later time intervals. Global subendocardial LGE is seen in
patients with more severe forms of the disease characterised by
a greater LV mass (fig 8). Image acquisition needs to start
earlier than the usual 10 minutes after contrast injection and
optimal results are achieved when imaging is started after
5 minutes. The combination of this typical LGE pattern with an
optimised T1 threshold between myocardium and blood has an
accuracy of 97% for making the correct diagnosis.43 However, as
amyloid is not always evenly distributed, a more patchy pattern
of LGE may also be seen in some patients. The main mechanism
of LGE in patients with amyloidosis differs from that seen in
patients with chronic myocardial infarction. Whereas myocyte
cell death and replacement fibrosis are responsible for the
increased partition coefficient of the contrast agent in the latter,
expansion of the interstitium by massive amyloid deposits
without myocyte death explains the less intense LGE in
amyloid heart disease.
Fabry’s disease
Storage diseases are important differential diagnoses in
patients with left ventricular hypertrophy. In Fabry’s disease,
accumulation of an abnormal glycoprotein occurs in the
myocyte due to a-galactosidase deficiency. CMR may detect
regional or global myocardial thickening44 and regional LGE is
seen at later and more severe stages of the disease.45 The
posterolateral wall is predominantly affected but the reason for
this is unknown.
Haemochromatosis
Death due to iron overload cardiomyopathy is common in
countries with a large population of patients with b-thalassaemia major. Cardiac failure can be avoided if intensive chelation
therapy is instituted at an early stage of myocardial iron
overload. Serum iron and hepatic iron are poor substitutes for
direct measurements of myocardial iron concentration. Noninvasive determination of the cardiac iron load is possible by
measuring myocardial relaxation time T2*.46 Myocardial T2*
correlates well with cardiac iron concentration measured from
biopsy specimens47 and T2* values ,20 ms are associated with
heart failure in patients with b-thalassaemia major. T2* CMR
measurements were the basis for a recent randomised trial
suggesting that a new chelating agent (deferiprone) can unload
myocardial iron faster than the standard chelator deferoxamine.48 Thus, regular determination of myocardial T2* should
be able to decrease the incidence of heart failure in patients
with thalassaemia because aggressive chelation therapy can be
started earlier.
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Sechtem, Mahrholdt, Vogelsberg
Practical implications for CMR in myocardial disease
Patients with myocardial disease as the basis of their clinical
presentation and echocardiographic findings should undergo
CMR if further aetiological differentiation is felt to be of clinical
value. As such patients may present with otherwise unexplained signs and objective findings of myocardial disease in
the presence of a ‘‘normal’’ echocardiogram, CMR should also
be considered in such cases. CMR may provide new anatomical
information in patients with poor echo windows, but the main
contribution of CMR is the LGE examination. Contrast
enhancement is non-specific, but the diagnosis of cardiomyopathy can be made. The definitive diagnosis often relies on the
findings of endomyocardial biopsy.
The main contributions of CMR are:
N
N
N
N
N
N
helping to make differential diagnosis between ischaemic
and dilated cardiomyopathy;
identifying patients with myocarditis;
diagnosing cardiac involvement in sarcoidosis and Chagas’
disease;
identifying patients with unusual forms of hypertrophic
cardiomyopathy and those with continuing myocardial
damage;
defining the sequelae of ablation treatment for hypertrophic
obstructive cardiomyopathy;
helping with the differential diagnosis in patients with left
ventricular hypertrophy by providing clues to the presence of
infiltrative cardiomyopathies.
.......................
Authors’ affiliations
U Sechtem, H Mahrholdt, H Vogelsberg, Division of Cardiology and
Pulmology, Robert-Bosch-Krankenhaus, Auerbachstrasse, Stuttgart,
Germany
Competing interests: None declared.
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5 Moon JC, Reed E, Sheppard MN, et al. The histologic basis of late gadolinium
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cardiomyopathy. J Am Coll Cardiol 2004;43:2260–4.
6 Boxt LM, Hsu D, Katz J, et al. Estimation of myocardial water content using
transverse relaxation time from dual spin-echo magnetic resonance imaging.
Magn Reson Imaging 1993;11:375–83.
7 Hiramitsu S, Morimoto S, Kato S, et al. Transient ventricular wall thickening in
acute myocarditis: a serial echocardiographic and histopathologic study. Jpn
Circ J 2001;65:863–6.
8 Reimer KA, Lowe JE, Rasmussen MM, et al. The wavefront phenomenon of
ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion
in dogs. Circulation 1977;56:786–94.
9 Wagner A, Mahrholdt H, Holly TA, et al. Contrast-enhanced MRI and routine
single photon emission computed tomography (SPECT) perfusion imaging for
detection of subendocardial myocardial infarcts: an imaging study. Lancet
2003;361:374–9.
10 Wu E, Judd RM, Vargas JD, et al. Visualisation of presence, location, and
transmural extent of healed Q-wave and non-Q-wave myocardial infarction.
Lancet 2001;357:21–8.
11 McCrohon JA, Moon JC, Prasad SK, et al. Differentiation of heart failure related
to dilated cardiomyopathy and coronary artery disease using gadoliniumenhanced cardiovascular magnetic resonance. Circulation 2003;108:54–9.
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12 Soriano CJ, Ridocci F, Estornell J, et al. Noninvasive diagnosis of coronary artery
disease in patients with heart failure and systolic dysfunction of uncertain
etiology, using late gadolinium-enhanced cardiovascular magnetic resonance.
J Am Coll Cardiol 2005;45:743–8.
13 Aretz HT. Diagnosis of myocarditis by endomyocardial biopsy. Med Clin North
Am 1986;70:1215–26.
14 De Cobelli F, Pieroni M, Esposito A, et al. Delayed gadolinium-enhanced cardiac
magnetic resonance in patients with chronic myocarditis presenting with heart
failure or recurrent arrhythmias. J Am Coll Cardiol 2006;47:1649–54.
15 Mahrholdt H, Wagner A, Judd RM, et al. Delayed enhancement cardiovascular
magnetic resonance assessment of non-ischaemic cardiomyopathies. Eur Heart J
2005;26:1461–74.
16 Davies MJ. The cardiomyopathies: an overview. Heart 2000;83:469–74.
17 Simonetti OP, Kim RJ, Fieno DS, et al. An improved MR imaging technique for
the visualization of myocardial infarction. Radiology 2001;218:215–23.
18 Ricciardi MJ, Wu E, Davidson CJ, et al. Visualization of discrete microinfarction
after percutaneous coronary intervention associated with mild creatine kinaseMB elevation. Circulation 2001;103:2780–3.
19 Hauck AJ, Kearney DL, Edwards WD. Evaluation of postmortem endomyocardial
biopsy specimens from 38 patients with lymphocytic myocarditis: implications for
role of sampling error. Mayo Clin Proc 1989;64:1235–45.
20 Friedrich MG, Strohm O, Schulz-Menger J, et al. Contrast media-enhanced
magnetic resonance imaging visualizes myocardial changes in the course of viral
myocarditis. Circulation 1998;97:1802–9.
21 Mahrholdt H, Goedecke C, Wagner A, et al. Cardiovascular magnetic
resonance assessment of human myocarditis: a comparison to histology and
molecular pathology. Circulation 2004;109:1250–8.
22 Mason JW, O’Connell JB, Herskowitz A, et al. A clinical trial of
immunosuppressive therapy for myocarditis. N Engl J Med 1995;333:269–75.
23 Mangin M, Mahrholdt H, Hager S, et al. Cardiovascular magnetic resonance
assessment of human myocarditis using a standardized combined right and left
ventricular endomyocardial biopsy protocol [abstract]. Circulation
2005;109(Suppl 2):145.
24 Abdel-Aty H, Boye´ P, Zagrosek A, et al. The sensitivity and specificity of contrastenhanced and T2-weighted cardiovascular magnetic resonance to detect acute
myocarditis. J Am Coll Cardiol 2005;45:1815–22.
25 Laissy JP, Hyafil F, Feldman LJ, et al. Differentiating acute myocardial infarction
from myocarditis: diagnostic value of early- and delayed-perfusion cardiac MR
imaging. Radiology 2005;237:75–82.
26 Wagner A, Schulz-Menger J, Dietz R, et al. Long-term follow-up of patients with
acute myocarditis by magnetic resonance imaging. MAGMA 2003;16:17–20.
27 Ku¨hl U, Pauschinger M, Seeberg B, et al. Viral persistence in the myocardium is
associated with progressive cardiac dysfunction. Circulation
2005;112:1965–70.
28 Mahrholdt H, Wagner A, Deluigi C, et al. Presentation, patterns of myocardial
damage and clinical course of viral myocarditis. Circulation
2006;114:1581–90.
29 Lenghaus C, Studdert MJ. Acute and chronic viral myocarditis. Acute diffuse
nonsuppurative myocarditis and residual myocardial scarring following infection
with canine parvovirus. Am J Pathol 1984;115:316–9.
30 Shirani J, Freant LJ, Roberts WC. Gross and semiquantitative histologic findings
in mononuclear cell myocarditis causing sudden death, and implications for
endomyocardial biopsy. Am J Cardiol 1993;72:952–7.
1527
31 Bowles NE, Ni J, Kearney DL, et al. Detection of viruses in myocardial tissues by
polymerase chain reaction. evidence of adenovirus as a common cause of
myocarditis in children and adults. J Am Coll Cardiol 2003;42:466–72.
32 Vignaux O. Cardiac sarcoidosis: spectrum of MRI features. AJR Am J Roentgenol
2005;184:249–54.
33 Smedema JP, Snoep G, van Kroonenburgh MP, et al. Evaluation of the accuracy
of gadolinium-enhanced cardiovascular magnetic resonance in the diagnosis of
cardiac sarcoidosis. J Am Coll Cardiol 2005;45:1683–90.
34 Rochitte CE, Oliveira PF, Andrade JM, et al. Myocardial delayed enhancement
by magnetic resonance imaging in patients with Chagas’ disease: a marker of
disease severity. J Am Coll Cardiol 2005;46:1553–8.
35 Rickers C, Wilke NM, Jerosch-Herold M, et al. Utility of cardiac magnetic
resonance imaging in the diagnosis of hypertrophic cardiomyopathy. Circulation
2005;112:855–61.
36 Moon JC, Fisher NG, McKenna WJ, et al. Detection of apical hypertrophic
cardiomyopathy by cardiovascular magnetic resonance in patients with nondiagnostic echocardiography. Heart 2004;90:645–9.
37 Choudhury L, Mahrholdt H, Wagner A, et al. Myocardial scarring in
asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy.
J Am Coll Cardiol 2002;40:2156–64.
38 Moon JC, Mogensen J, Elliott PM, et al. Myocardial late gadolinium enhancement
cardiovascular magnetic resonance in hypertrophic cardiomyopathy caused by
mutations in troponin I. Heart 2005;91:1036–40.
39 Moon JC, McKenna WJ, McCrohon JA, et al. Toward clinical risk assessment in
hypertrophic cardiomyopathy with gadolinium cardiovascular magnetic
resonance. J Am Coll Cardiol 2003;41:1561–7.
40 van Dockum WG, ten Cate FJ, ten Berg JM, et al. Myocardial infarction after
percutaneous transluminal septal myocardial ablation in hypertrophic obstructive
cardiomyopathy: evaluation by contrast-enhanced magnetic resonance imaging.
J Am Coll Cardiol 2004;43:27–34.
41 Haghi D, Papavassiliu T, Fluchter S, et al. Variant form of the acute apical
ballooning syndrome (takotsubo cardiomyopathy): observations on a novel
entity. Heart 2006;92:392–4.
42 Sharkey SW, Lesser JR, Zenovich AG, et al. Acute and reversible
cardiomyopathy provoked by stress in women from the United States. Circulation
2005;111:472–9.
43 Maceira AM, Joshi J, Prasad SK, et al. Cardiovascular magnetic resonance in
cardiac amyloidosis. Circulation 2005;111:186–93.
44 Weidemann F, Breunig F, Beer M, et al. Improvement of cardiac function during
enzyme replacement therapy in patients with Fabry disease: a prospective strain
rate imaging study. Circulation 2003;108:1299–301.
45 Weidemann F, Breunig F, Beer M, et al. The variation of morphological and
functional cardiac manifestation in Fabry disease: potential implications for the
time course of the disease. Eur Heart J 2005;26:1221–7.
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resonance for the early diagnosis of myocardial iron overload. Eur Heart J
2001;22:2171–9.
47 Mavrogeni SI, Markussis V, Kaklamanis L, et al. A comparison of magnetic
resonance imaging and cardiac biopsy in the evaluation of heart iron overload in
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overload in thalassemia major: new data, new questions. Blood
2006;107:3436–41.
www.heartjnl.com
REVIEW
Cardiac magnetic resonance in myocardial disease
Udo Sechtem, Heiko Mahrholdt, Holger Vogelsberg
...................................................................................................................................
Heart 2007;93:1520–1527. doi: 10.1136/hrt.2005.067355
For a number of patients it is difficult to diagnose the cause of
cardiac disease. In such patients cardiac magnetic resonance is
useful for helping to make a differential diagnosis between
ischaemic and dilated cardiomyopathy; identifying patients with
myocarditis; diagnosing cardiac involvement in sarcoidosis and
Chagas’ disease; identifying patients with unusual forms of
hypertrophic cardiomyopathy and those with continuing
myocardial damage; and defining the sequelae of ablation
treatment for hypertrophic obstructive cardiomyopathy.
.............................................................................
P
atients presenting with cardiac disease usually
become aware of their health problem by
recognising one of three types of symptoms:
signs of heart failure, chest discomfort or arrhythmias. Another group of patients may require more
detailed investigation owing to asymptomatic ECG
changes which appeared during a routine medical
check-up. Patients presenting with heart-related
problems usually undergo an exercise stress test
and transthoracic echocardiography. The results of
these tests in combination with a careful history
will distinguish between those with coronary
artery disease, valvular heart disease, cardiomyopathies or other less common variants of cardiac
problems. However, in a subgroup of patients it is
difficult to identify the cause of the problem even
after cardiac catheterisation and those patients
often have conditions where cardiac function is
impaired, but this impairment cannot be explained
by coronary artery disease or abnormal loading
conditions. It is in these patients where cardiac
magnetic resonance (CMR) will be clinically helpful to characterise further the pathophysiology
underlying the patient’s problem and help to make
a diagnosis.
DILATED CARDIOMYOPATHY (DCM) AND
CHRONIC VIRAL MYOCARDITIS
See end of article for
authors’ affiliations
........................
Correspondence to:
Professor Dr U Sechtem,
Division of Cardiology and
Pulmology, Robert-BoschKrankenhaus,
Auerbachstrasse 110,
D-70376 Stuttgart,
Germany; udo.sechtem@
rbk.de
Accepted 21 May 2006
Published Online First
6 June 2006
........................
www.heartjnl.com
In patients with symptoms and signs of heart
failure of recent onset, echocardiography often
discloses an enlarged, poorly contractile left
ventricle (LV) and sometimes also signs of right
ventricular dysfunction. As the patients often also
report chest pain the differential diagnosis of the
cause of heart failure is broad. The challenge is to
distinguish between ischaemia, infection, inflammation or ‘‘idiopathic’’ disease. In patients without
a typical history of coronary artery disease with
myocardial infarction an ischaemic cause of
ventricular dysfunction is still commonly ruled
out by routine coronary angiography. The assumption is that the finding of stenosed or occluded
coronary arteries is synonymous with the presence
of ischaemic scar or hibernation. A perfect
demonstration of an ischaemic cause of heart
failure requires demonstration of an ischaemic
scar or hibernation, in addition to depicting
coronary morphology by coronary angiography or
computed tomography.1 Perfusion defects shown
by nuclear myocardial perfusion imaging usually
indicate an ischaemic scar, but such defects can
also by found in patients with DCM. Segmental
wall motion abnormalities are the mainstay of the
echocardiographic differentiation, but they may
not always distinguish between the two entities.2
Myocardial tissue differentiation by echocardiography is still in its infancy and relies on indirect
signs such as differences in strain rate.3
Late gadolinium enhancement (LGE) is a new
tool provided by CMR.4 LGE depicts areas of
myocardial necrosis and fibrosis with high spatial
resolution and accurately reflects ‘‘true’’ changes
demonstrated by pathology both in animal models4
and human disease.5 When appropriate pulse
sequences optimised to reflect differences in the
spin–spin relaxation time T2 are used, CMR may
also be able to depict tissue oedema.6 Oedema
often accompanies inflammatory myocardial disease.7
How can CMR be used for distinguishing
between patients with ischaemic and non-ischaemic heart failure? Ischaemic scar is either subendocardial or transmural.8 CMR is sensitive in
detecting even small amounts of subendocardial
infarction.9 Thus it is also sensitive in detecting
ischaemic heart failure as some degree of scar will
usually be present in ischaemically injured, poorly
contractile ventricles. On the other hand, subendocardial enhancement should be absent in
patients with normal coronary arteries and left
ventricular dysfunction. Indeed, several groups
have now confirmed that LGE-CMR finds scar
tissue in almost all patients with a previously
identified infarct related artery but only rarely in
patients with non-ischaemic cardiomyopathy or
healthy volunteers (table 1).10–12 Peculiar findings
seen in patients without coronary artery disease
are longitudinal striae of mid-wall enhancement,
clearly different from the subendocardial or
transmural enhancement pattern seen in patients
with coronary artery disease (fig 1).
Recently, the mid-wall LGE pattern was found
to be associated with active or borderline myocarditis by Dallas criteria13 in patients with a clinical
presentation of chronic myocarditis and depressed
left ventricular function or repetitive ventricular
Abbreviations: CMR, cardiac magnetic resonance; DCM,
dilated cardiomyopathy; EMB, endomyocardial biopsy;
HCM, hypertrophic cardiomyopathy; LGE, late gadolinium
enhancement; LV, left ventricle; PVB19, parvovirus B19
Cardiac magnetic resonance in myocardial disease
1521
Table 1 CMR distinguishes between ischaemic and non-ischaemic cardiomyopathy
Reference
n
Wu et al10
71
11
McCrohon et al 90
12
71
Soriano et al
Inclusion criteria
Proven MI or dilated cardiomyopathy
Clinical heart failure, coronary angiography
Clinical heart failure, systolic LV dysfunction,
no CAD history, no previous MI, no Q-waves
LVEF
(%)
CAD Subendo LGE
(n)
No (%)
Mid-wall LGE No CAD
No (%)
(n)
Subendo LGE
No (%)
Mid-wall LGE
No (%)
NA
33–39
51
27
48 (94)
27 (100)
0 (0)
0 (0)
20
63
0 (0)
8 (13)
0 (0)
18 (28)
27
26
21 (81)
96/104 (92)
3 (11)
3/104 (3)
45
4 (9)
12/128 (9)
4 (9)
22/128 (17)
Total
CAD, coronary artery disease; LVEF, left ventricular ejection fraction; MI, myocardial infarction; Subendo, subendothelial.
arrhythmias.14 This pattern was seen just as often in patients
with active myocarditis (43%) as in those with borderline
myocarditis (44%). Interestingly, patients with a clinical
diagnosis of dilated cardiomyopathy and mid-wall LGE have
a worse prognosis, as measured by unplanned admission to
hospital or death, than patients with a similar degree of left
ventricular dysfunction but no mid-wall LGE (Prasad S,
unpublished data).
What is the histological basis of such non-endocardial
myocardial enhancement in patients with DCM which does
not correspond to the perfusion bed of a coronary artery?
Although inflammation seems to play a part with such
intramyocardial or epicardial changes,14 inflammation is unlikely to be the sole cause of LGE. As in LGE associated with
infarction, an important mechanism of enhancement is the
expansion of extracellular space associated with myocardial
necrosis14 and later fibrosis.15 Myocyte necrosis is a feature of
acute myocarditis as defined by the Dallas criteria, and
myocardial fibrosis is usually found at postmortem examinations in patients with a diagnosis of DCM. Myocyte necrosis in
myocarditis is usually disseminated, but larger confluent areas
may exist.16 Fibrotic changes may also be diffuse or more
patchy. The LGE technique is unlikely to detect diffuse necrotic
or fibrotic changes as it is designed to optimise contrast
between normal and necrotic myocardium in patients with
focal ischaemic necrosis.17 Hence, no enhancement will be seen
by LGE-CMR in patients with diffuse myocardial damage. In
contrast, LGE-CMR does have sufficient spatial resolution to
resolve small foci of myocardial necrosis or fibrosis in vivo.18 It
is currently unknown whether the amount of fibrosis seen by
CMR has prognostic value.
ACUTE VIRAL MYOCARDITIS
Clinical symptoms in patients with acute myocarditis may be
absent and the only clue to the presence of the disease may be
changes in the ECG. At the other end of the spectrum, patients
may come to the hospital in cardiogenic shock. As myocarditis
Patient A
Patient B
may be associated with systemic viral illness, patients may
report tiredness, muscle aches, chest pain and palpitations.
There are three more dramatic modes of presentation associated
with myocarditis. First, myocarditis may manifest as acute
onset of heart failure in a previously healthy person. Second, it
may masquerade as an acute coronary syndrome. Third,
arrhythmias including ventricular tachycardia may be the
leading symptom, sometimes manifesting as sudden cardiac
death. Establishing the diagnosis of myocarditis is difficult as
there are currently no non-invasive tools to verify the diagnosis
and assess the extent of myocardial involvement. The ultimate
proof that the patient has myocarditis is provided by
endomyocardial biopsy (EMB), which may demonstrate the
typical inflammatory infiltrate in the myocardium. Using
molecular hybridisation or PCR methods, it is possible to
identify the causative viral agent. However, myocarditis is a
patchy disease, which may explain the sampling error limiting
the diagnostic value of endomyocardial biopsy.19
Friedrich et al were the first to propose CMR for non-invasive
diagnosis of clinically acute myocarditis.20 They observed that
the myocardium in patients with the clinical manifestations of
myocarditis showed hyperenhancement relative to skeletal
muscle on T1-weighted images. However, the imaging protocol
used in that study yielded a low contrast between inflamed and
normal myocardium and suffered from image artefacts.
New contrast-enhanced CMR techniques such as the one
employed for infarct imaging17 provide an improvement in
contrast between diseased and normal myocardium of up to
500% when compared with the protocol used by Friedrich et al.
When these new inversion recovery gradient echo techniques
are used in patients with clinically suspected myocarditis
(history of respiratory or gastrointestinal symptoms with
8 weeks of admission in combination with fatigue/malaise,
chest pain, dyspnoea or tachycardia plus ECG changes such as
conduction block, ST abnormalities, supraventricular tachyarrhythmia or ventricular tachycardia) LGE is found in up to 90%
of the patients.21 The regions of LGE have a patchy distribution
Figure 1 Short-axis images in two patients
presenting with heart failure, enlarged left
ventricle and systolic dysfunction. The
corresponding contrast cardiac magnetic
resonance images demonstrate nearly
transmural late gadolinium enhancement
(LGE) in the anteroseptal wall consistent with
a prior myocardial infarction in the patient
with ischaemic heart disease (patient A),
whereas typical mid-wall stria-type LGE is
present in the patient with non-ischaemic
cardiomyopathy (patient B).
www.heartjnl.com
1522
Sechtem, Mahrholdt, Vogelsberg
Figure 2 Left and middle panel: basal and
mid-ventricular short-axis late gadolinium
enhancement-cardiac magnetic resonance
image in a 26-year-old man with the clinical
picture of acute myocarditis demonstrating
epicardial enhancement in the posterolateral
aspects of the left ventricle (arrows). The
three-chamber view (right panel) shows
prominent bright foci of enhancement in the
lateral wall (arrows). Biopsy disclosed
parvovirus B19 infection.
throughout the LV. They are frequently located in the lateral
free wall (fig 2) and originate from the epicardial quartile of
that wall. Another commonly seen pattern is the mid-wall stria
pattern in the basal interventricular septum mentioned above
in patients with chronic myocarditis.
Biopsy specimens obtained from the area of LGE show acute
or borderline myocarditis13 in a higher percentage than reported
in the literature.22 However, one has to consider that an increase
in the number of activated macrophages (.14/high power
field) was an additional criterion for making the diagnosis of
borderline myocarditis in the study by Mahrholdt et al.21 This
represents an extension of the original Dallas criteria,13 and an
increased sensitivity of EMB can hence be expected.
Irrespective of this point, myocarditis is seen less consistently
in patients in whom the biopsy cannot be obtained from the
region of contrast enhancement (found in only one of seven
patients in the study by Mahrholdt et al21). Thus, CMR-guided
biopsy in the right or the left ventricle may result in a higher
yield of positive findings than routine right ventricular biopsy.23
As mentioned above, the inability to demonstrate diffuse
myocardial changes as encountered in diffuse myocarditis with
diffuse oedema formation is a disadvantage of the LGE
technique. Even localised oedema without accompanying
myocyte death might not result in sufficient increase in
T1/pre contrast
T2
Late post contrast
www.heartjnl.com
T1/early post contrast
extracellular space to cause LGE. Thus, the sensitivity of LGE
to detect milder forms of myocarditis may be suboptimal.
Recently, it has been suggested that CMR imaging optimised at
detecting inflammation or oedema may be more sensitive for
identifying patients with acute myocarditis.24 Three different
pulse sequences were compared in patients with cardiac
symptoms such as angina, dyspnoea or palpitations accompanied by ECG changes such as ST-segment changes or
conduction defects and raised serum markers. A T2-weighted
triple inversion recovery pulse sequence showed a significantly
higher global myocardial signal intensity in patients than in
volunteers, although there was overlap. A cut-off value of 1.9
had a sensitivity of 84% and a specificity of 74% to identify the
disease. A T1-weighted spin echo before and shortly after
contrast injection (as described by Friedrich et al20) yielded a
significantly higher global myocardial relative enhancement in
patients than in volunteers. A cut-off value of 4.0 had a
sensitivity of 80% and a specificity of 73% to identify
myocarditis. The sensitivity of a inversion recovery gradient
echo pulse sequence (LGE sequence) started 10 minutes after
contrast injection was lower at only 44% (fig 3), but the
specificity was high (100%). The best diagnostic performance
was obtained when any two of the criteria obtained by the three
techniques were positive in a given patient.24 One needs to
Figure 3 Cardiovascular magnetic
resonance findings in a patient with acute
chest pain and ST elevations in II, III, aVF as
well as negative T-waves in II, III, aVF, V5–
V6. The patient also had a mild increase of
cardiac markers. (Top) Pre- and postcontrast
axial T1-weighted spin-echo images of the
same slice. Global relative enhancement was
increased (4.1). (Middle) T2-weighted
images in three short-axis slices. Note the
posterolateral focal high T2 signal
(arrowheads) in the basal slice with apparent
focal increase in myocardial thickness.
(Bottom) Corresponding late enhancement
images: no evidence of late gadolinium
enhancement. Reprinted with permission
from Abdel-Aty H, Boye´ P, Zagrosek A, et al.
The sensitivity and specificity of
contrastenhanced and T2-weighted
cardiovascular magnetic resonance to detect
acute myocarditis. J Am Coll Cardiol
2005;45:1815–22.24
Cardiac magnetic resonance in myocardial disease
ACUTE
1523
Figure 4 Serial late gadolinium
enhancement (LGE) images in another
patient with acute parvovirus B19
myocarditis. Upper panel: short-axis (left)
and four-chamber view (right) images show
prominent enhancement of the lateral wall
extending almost throughout the entire wall
but originating from the epicardium
(arrows). Lower panel: at follow-up LGEcardiac magnetic resonance 4 months later,
the inflammatory lesions have faded and
become smaller. Reprinted with permission
from Mahrholdt H, Goedecke C, Wagner A,
et al. Cardiovascular magnetic resonance
assessment of human myocarditis: a
comparison to histology and molecular
pathology. Circulation 2004;109:1250–8.21
FU (12 weeks)
remember, however, that in this series the preferred method for
identifying myocarditis was the clinical presentation of the
patient, and EMB was not performed.
CMR is also helpful for differentiating between acute injury
due to inflammation and ischaemic injury.25 Whereas patients
with acute myocardial infarction show segmental early
subendocardial defects on perfusion MRI, with corresponding
segmental subendocardial or transmural LGE in a vascular
distribution, patients with myocarditis have no early defect and
focal or diffuse non-segmental non-subendocardial LGE.
Moreover, CMR gives first insights into the clinical course of
patients with myocarditis. It appears that T1 contrast enhancement decreases to almost normal values within 4 weeks after
the initial clinical presentation in most patients.26 The area of
LGE also decreases in many patients and enhancement may
disappear completely (fig 4). However, the decrease in
enhancement is only moderately correlated with the improvement in ejection fraction.21
In Germany, PVB19 is currently the most commonly
encountered causative agent, followed by adenovirus and
human herpes virus type 6.21 27 Parvovirus associated myocarditis often shows LGE of the epicardial portions of the free
lateral wall of the LV.28 Interestingly, epicardial lesions are also
the predominant findings in canine parvovirus myocarditis.29
This finding may, however, not be parvovirus specific as in the
United States gross lesions have also been found in epicardial
portions of the posterolateral free wall in patients dying
suddenly with acute myocarditis,30 although parvovirus
Figure 5 Spin-echo (upper panel) and late
gadolinium enhancement-cardiac magnetic
resonance (LGE-CMR; lower panel) images
in a patient with biopsy proven with
pulmonary sarcoidosis. A diffuse signal is
seen in both lungs on spin-echo images. LGE
short-axis images (three images from the left
in the lower panel from base to apex)
demonstrate inferior and lateral
enhancement not dissimilar to that seen in
myocarditis. With steroid treatment,
symptoms improved and myocardial
enhancement became fainter.
www.heartjnl.com
1524
Sechtem, Mahrholdt, Vogelsberg
Figure 6 Patient with asymmetric
hypertrophy and small scars at junctions
between the left and right ventricles (arrows)
shown by late gadolinium enhancementcardiac magnetic resonance. Left: short-axis
image. Right: two-chamber view parallel to
the interventricular septum.
infection is not common in the United States.31 In contrast, the
peculiar pattern of a sandwiched stripe of late enhancement
within the interventricular septum is more frequently found in
herpes virus or mixed infections caused by herpes virus and
parvovirus.28 Intraseptal lesions are also seen at necropsy in
patients dying of active myocarditis.19
OTHER FORMS OF INFLAMMATORY
CARDIOMYOPATHY
In patients with clinical signs of cardiac sarcoidosis (arrhythmias, conduction disturbances, heart block, pericardial effusion
or sudden death), cine CMR usually demonstrates regional wall
motion abnormalities and may also show wall thickening of the
affected region.32 T2-weighted imaging may demonstrate
diffuse regional signal increase. LGE often shows focal areas
of inflammation or fibrosis, or both,33 (fig 5) and contrast
enhancement may show patterns of epicardial enhancement
similar to that seen in myocarditis. As in patients with
myocarditis, findings of T2 and LGE images are not necessarily
concordant. Although CMR findings may be non-specific, the
high sensitivity makes CMR an attractive first-line non-invasive
method for early diagnosis and follow-up of cardiac sarcoidosis.
Chagas’ disease is an inflammatory form of myocardial
disease caused by the protozoan Trypanosoma cruzi. Although
the inflammatory myocardial process is crucial for parasite
control, inflammation may become progressive, resulting in
chronic disease that is characterised by myocarditis associated
with prominent fibrosis and cardiac dysfunction. CMR demonstrates myocardial LGE in two-thirds of patients diagnosed
with Chagas’ disease,34 and the incidence increases with
increasing severity of cardiac dysfunction and is most pronounced in patients with severe ventricular arrhythmias. LGE
patterns may be similar to viral myocarditis, affecting the
epicardial portion of the LV free wall.34 Thus, CMR enables the
quantification of myocardial inflammation and fibrosis in
Chagas’ disease, adding important information on disease
severity, and may become useful for early identification of
cardiac involvement in the subclinical phases of the disease
process.
HYPERTROPHIC CARDIOMYOPATHY
CMR has also become a useful technique in the management of
patients
with
hypertrophic
cardiomyopathy
(HCM).
Differentiating between HCM and other forms of hypertrophy
has remained a substantial challenge for imaging techniques.
Although most patients with HCM have a typical asymmetric
pattern of hypertrophy affecting the interventricular septum
more than the posterolateral wall, concentric, apical and other
www.heartjnl.com
atypical distributions of hypertrophy do exist. These atypical
forms of hypertrophy, in particular, may be difficult to
recognise by echocardiography. CMR can identify such regions
of LV hypertrophy and thus represents a powerful supplemental
imaging test with distinct diagnostic advantages for selected
patients with HCM.35 36
CMR can also be used to assess myocardial tissue characteristics in vivo by applying the late enhancement technique to
patients with HCM. Myocardial scarring is a common finding in
patients with HCM and may be prognostically important.
Scarring occurs mostly in hypertrophied regions and is usually
patchy with multiple foci, predominantly affecting the midventricular wall.37 However, the location of scarring does not
correspond to the perfusion territories of the epicardial
coronary arteries. It is currently not clear whether increased
numbers of structurally abnormal intramural coronary arteries
within areas of scarred myocardium have a causal role in
producing myocardial ischaemia leading to scarring. In patients
with small areas of scarring, the junctions of the interventricular septum and the right ventricular walls are commonly
affected (fig 6). In patients with disease caused by mutations in
the troponin I gene, focal fibrosis is usually not detected by
LGE-CMR before left ventricular hypertrophy and ECG
abnormalities are present.38 However, once hypertrophy is
present, LGE is common and the extent correlates with adverse
clinical measures. This suggests that focal fibrosis is closely
linked to disease development. The extent of scarring measured
by CMR correlates with conventional risk markers, but it is
currently not clear whether the extent of scarring in the CMR
will be more predictive of serious arrhythmic events than the
current risk stratification based on risk factors.
Patients with severe forms of hypertrophic cardiomyopathy
may develop progressive left ventricular impairment associated
with progressive interstitial fibrosis, myocardial disarray, small
vessel disease, and microscopic scarring leading to wall
thinning. CMR demonstrates a greater extent of hyperenhancement in patients with clinically progressive disease and this is
associated with thinning of previously grossly hypertrophied
myocardium.39
Similar to (colour) Doppler echocardiography, CMR can depict
and quantify the turbulent jet in the left ventricular outflow tract
in patients with the obstructive form of HCM. A unique advantage
of CMR is the opportunity for monitoring and quantifying the
changes induced by septal ablation of the obstructive lesion (fig 7).
The remodelling of the left ventricular outflow tract can be serially
monitored during the healing process.40
Thus, CMR provides comprehensive information on anatomy,
function and tissue composition in patients with HCM.
Cardiac magnetic resonance in myocardial disease
A
B
C
D
Although the value of CMR as compared with echocardiography is not clearly defined yet, CMR will be useful in patients for
whom complete information cannot be obtained by echocardiography.
OTHER CARDIOMYOPATHIES
Stress-induced cardiomyopathy
Left apical ballooning (takotsubo cardiomyopathy) is a clinical
entity characterised by acute but rapidly reversible left
1525
Figure 7 Contrast-enhanced images
20 minutes after intravascular administration
of gadolinium-DTPA in two patients with
hypertrophic obstructive cardiomyopathy
1 month after percutaneous transluminal
septal myocardial ablation. (A, B) Threechamber view and short-axis view in a
patient with transmural septal infarction.
(C, D) Comparable views in a patient with
myocardial infarction located exclusively on
the right ventricular side of the
interventricular septum. Reprinted with
permission from van Dockum WG, ten Cate
FJ, ten Berg JM, et al. Myocardial infarction
after percutaneous transluminal septal
myocardial ablation in hypertrophic
obstructive cardiomyopathy: evaluation by
contrast-enhanced magnetic resonance
imaging. J Am Coll Cardiol 2004;43:27–
34.40
ventricular systolic dysfunction in the absence of atherosclerotic coronary artery disease, often triggered by profound
psychological stress. Catecholamine production and myocardial
stunning are thought to be involved pathophysiologically and
the distal portion of the LV is most commonly affected. CMR
contributes to an understanding of this new entity by
demonstrating the absence of irreversible injury41 (LGE) but
oedema formation on T2-weighted images. CMR also aids in
clearly identifying segmental wall-motion abnormalities
Figure 8 Subendocardial enhancement on late gadolinium enhancement short-axis (left from base to apex) and two-chamber view (parallel to
interventricular septum) images in a patient with immunoglobulin light chain (AL) cardiac amyloidosis due to multiple myeloma. Note that image acquisition
needs to be started earlier than the usual 10 minutes after contrast injection as the contrast agents quickly diffuse into the amyloid-filled enlarged interstitial
space, and differential enhancement may be absent at later phases of the diffusion process. In patients with possible amyloid disease (eg, in all patients with
unexplained left ventricular hypertrophy) and abnormal findings on TI scout images, an early series of contrast images should be acquired.
www.heartjnl.com
1526
encompassing the left ventricular myocardium in multiple
coronary arterial vascular territories.42 In patients with severe
haemodynamic impairment, CMR may also demonstrate
involvement of the right ventricle.
Infiltrative cardiomyopathies
Cardiac involvement is common in systemic amyloidosis. It is a
major determinant of treatment options and prognosis and is a
frequent cause of death. Myocardial disease is often the only
manifestation of transthyretin amyloidosis. Storage of proteins
in the insoluble fibrillar amyloid conformation occurs principally in the myocardial interstitium, with a preference for the
subendocardial space. Clinically, patients present with signs of
diastolic heart failure progressing to restrictive cardiomyopathy.
Relaxation time T1 measured from T1 maps is significantly
lower in the subendocardial space of patients with amyloidosis
than in hypertensive controls. Moreover, within patients,
subendocardial T1 is lower than T1 in the subepicardium for
the first 8 minutes after the administration of a gadoliniumbased contrast agent.43 This difference is no longer apparent at
later time intervals. Global subendocardial LGE is seen in
patients with more severe forms of the disease characterised by
a greater LV mass (fig 8). Image acquisition needs to start
earlier than the usual 10 minutes after contrast injection and
optimal results are achieved when imaging is started after
5 minutes. The combination of this typical LGE pattern with an
optimised T1 threshold between myocardium and blood has an
accuracy of 97% for making the correct diagnosis.43 However, as
amyloid is not always evenly distributed, a more patchy pattern
of LGE may also be seen in some patients. The main mechanism
of LGE in patients with amyloidosis differs from that seen in
patients with chronic myocardial infarction. Whereas myocyte
cell death and replacement fibrosis are responsible for the
increased partition coefficient of the contrast agent in the latter,
expansion of the interstitium by massive amyloid deposits
without myocyte death explains the less intense LGE in
amyloid heart disease.
Fabry’s disease
Storage diseases are important differential diagnoses in
patients with left ventricular hypertrophy. In Fabry’s disease,
accumulation of an abnormal glycoprotein occurs in the
myocyte due to a-galactosidase deficiency. CMR may detect
regional or global myocardial thickening44 and regional LGE is
seen at later and more severe stages of the disease.45 The
posterolateral wall is predominantly affected but the reason for
this is unknown.
Haemochromatosis
Death due to iron overload cardiomyopathy is common in
countries with a large population of patients with b-thalassaemia major. Cardiac failure can be avoided if intensive chelation
therapy is instituted at an early stage of myocardial iron
overload. Serum iron and hepatic iron are poor substitutes for
direct measurements of myocardial iron concentration. Noninvasive determination of the cardiac iron load is possible by
measuring myocardial relaxation time T2*.46 Myocardial T2*
correlates well with cardiac iron concentration measured from
biopsy specimens47 and T2* values ,20 ms are associated with
heart failure in patients with b-thalassaemia major. T2* CMR
measurements were the basis for a recent randomised trial
suggesting that a new chelating agent (deferiprone) can unload
myocardial iron faster than the standard chelator deferoxamine.48 Thus, regular determination of myocardial T2* should
be able to decrease the incidence of heart failure in patients
with thalassaemia because aggressive chelation therapy can be
started earlier.
www.heartjnl.com
Sechtem, Mahrholdt, Vogelsberg
Practical implications for CMR in myocardial disease
Patients with myocardial disease as the basis of their clinical
presentation and echocardiographic findings should undergo
CMR if further aetiological differentiation is felt to be of clinical
value. As such patients may present with otherwise unexplained signs and objective findings of myocardial disease in
the presence of a ‘‘normal’’ echocardiogram, CMR should also
be considered in such cases. CMR may provide new anatomical
information in patients with poor echo windows, but the main
contribution of CMR is the LGE examination. Contrast
enhancement is non-specific, but the diagnosis of cardiomyopathy can be made. The definitive diagnosis often relies on the
findings of endomyocardial biopsy.
The main contributions of CMR are:
N
N
N
N
N
N
helping to make differential diagnosis between ischaemic
and dilated cardiomyopathy;
identifying patients with myocarditis;
diagnosing cardiac involvement in sarcoidosis and Chagas’
disease;
identifying patients with unusual forms of hypertrophic
cardiomyopathy and those with continuing myocardial
damage;
defining the sequelae of ablation treatment for hypertrophic
obstructive cardiomyopathy;
helping with the differential diagnosis in patients with left
ventricular hypertrophy by providing clues to the presence of
infiltrative cardiomyopathies.
.......................
Authors’ affiliations
U Sechtem, H Mahrholdt, H Vogelsberg, Division of Cardiology and
Pulmology, Robert-Bosch-Krankenhaus, Auerbachstrasse, Stuttgart,
Germany
Competing interests: None declared.
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