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Late Gadolinium Enhancement Magnetic Resonance
Imaging in the Diagnosis and Prognosis of Endomyocardial
Fibrosis Patients
Vera M.C. Salemi, MD, PhD; Carlos E. Rochitte, MD, PhD; Afonso A. Shiozaki, MD;
Joalbo M. Andrade, MD, PhD; José R. Parga, MD, PhD; Luiz F. de Ávila, MD, PhD;
Luiz A. Benvenuti, MD, PhD; Ismar N. Cestari, MD, PhD; Michael H. Picard, MD;
Raymond J. Kim, MD; Charles Mady, MD, PhD
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Background—Endocardial fibrous tissue (FT) deposition is a hallmark of endomyocardial fibrosis (EMF). Echocardiography is a first-line and the standard technique for the diagnosis of this disease. Although late gadolinium enhancement
(LGE) cardiovascular magnetic resonance (CMR) allows FT characterization, its role in the diagnosis and prognosis of
EMF has not been investigated.
Methods and Results—Thirty-six patients (29 women; age, 54⫾12 years) with EMF diagnosis after clinical evaluation and
comprehensive 2-dimensional Doppler echocardiography underwent cine-CMR for assessing ventricular volumes,
ejection fraction and mass, and LGE-CMR for FT characterization and quantification. Indexed FT volume (FT/body
surface area) was calculated after planimetry of the 8 to 12 slices obtained in the short-axis view at end-diastole
(mL/m2). Surgical resection of FT was performed in 16 patients. In all patients, areas of LGE were confined to the
endocardium, frequently as a continuous streak from the inflow tract extending to the apex, where it was usually most
prominent. There was a relation between increased FT/body surface area and worse New York Heart Association
functional class and with increased probability of surgery (P⬍0.05). The histopathologic examination of resected FT
showed typical features of EMF with extensive endocardial fibrous thickening, proliferation of small vessels, and scarce
inflammatory infiltrate. In multivariate analysis, the patients with FT/body surface area ⬎19 mL/m2 had an increased
mortality rate, with a relative risk of 10.8.
Conclusions—Our study provides evidence that LGE-CMR is useful in the diagnosis and prognosis of EMF through
quantification of the typical pattern of FT deposition. (Circ Cardiovasc Imaging. 2011;4:304-311.)
Key Words: myocardial cardiomyopathy disease 䡲 endomyocardial fibrosis 䡲 restrictive cardiomyopathy 䡲 heart failure
䡲 magnetic resonance imaging 䡲 gadolinium 䡲 prognosis
E
exercise limitations.2 Clinical treatment is often unsatisfactory, and FT resection is the treatment of choice for patients
in New York Heart Association (NYHA) functional classes
III and IV.3
ndomyocardial fibrosis (EMF) is the most frequent
restrictive cardiomyopathy, affecting about 12 million
people in the world.1 It is characterized by fibrotic tissue (FT)
deposition in the endocardium of the inflow tract and apex of
one or both ventricles. Ventricular morphology is usually
distorted with normal or reduced volumes, whereas atrial
volumes are increased. The cause of EMF is unknown;
however, early hypereosinophilia may play a role in its
pathogenesis.1 Fibrosis of the subvalvular apparatus and
chords leads to atrioventricular valve regurgitation. Diastolic
dysfunction is responsible for the severe heart failure (HF) in
EMF patients and plays an important role in determining
Clinical Perspective on p 311
Echocardiography is a first-line and the gold standard
noninvasive technique for diagnosing EMF.4,5 It enables the
identification of the disease in early stages, the quantification
of the degree of morphological and hemodynamic compromise, and assessment of changes over time or with surgery.5
However, echocardiography is unable to fully characterize
Received May 11, 2010; accepted March 2, 2011.
From the Cardiomyopathy Unit (V.M.C.S., C.M.), Magnetic Resonance Section (C.E.R., A.A.S., J.M.A., J.R.P., L.F.d.A.), Laboratory of Pathology
(L.A.B.), and Biomedical Technology Center (I.N.C.) from Heart Institute (InCor) da Faculdade de Medicina da Universidade de São Paulo, São Paulo,
Brazil; the Cardiology Division and Cardiac Ultrasound Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, MA (M.H.P.);
and Duke Cardiovascular Magnetic Resonance Center, Department of Medicine and Department of Radiology, Duke University Medical Center, Durham,
NC (R.J.K.).
Guest Editor for this article was Andrew M. Taylor, MD.
The online-only Data Supplement is available at http://circimaging.ahajournals.org/cgi/content/full/CIRCIMAGING.110.950675/DC1.
Correspondence to Vera Maria Cury Salemi, MD, PhD, Av. Jandira 185 Apt 41B Indianópolis, São Paulo, Brazil, 04080 – 000. E-mail
[email protected]
© 2011 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org
304
DOI: 10.1161/CIRCIMAGING.110.950675
Salemi et al
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FT, and it may not fully differentiate EMF from other cardiac
diseases presenting as left ventricular (LV) apical obliteration, such as apical hypertrophic cardiomyopathy,1 cardiac
tumors,1,6 apical thrombus, or noncompaction of the ventricular myocardium.7 In patients with predominantly right ventricular (RV) involvement, the differential diagnoses includes
Ebstein anomaly1,8 and constrictive pericarditis.1 Contrast
ventriculography was at first considered the gold standard
method for EMF diagnosis,9 but, with improvements in
echocardiographic images quality, it is no longer routinely
performed.1 In addition to its risk, endomyocardial biopsy
allows the diagnosis in only about 50% of the patients.10
Cardiovascular magnetic resonance (CMR) provides detailed
information on ventricular morphology and function, including
excellent visualization of the ventricular apex. Late gadolinium
enhancement (LGE)-CMR allows the evaluation of the presence
of myocardial inflammation, fibrosis, and injury caused by a
relative accumulation of gadolinium that occurs in these conditions as the result of slower washout kinetics and the increased
extracellular volume.11,12 Precise EMF diagnosis and evaluation
of fibrosis may allow surgical intervention in a less advanced
stage of the disease to improve quality of life and prognosis.13,14
The goal of the present study was to investigate the role of
LGE-CMR in the diagnosis and prognosis of EMF.
Methods
Study Population and Groups
Inclusion criteria were age ⬎18 years, a clinical diagnosis of
diastolic HF, defined by the finding of typical symptoms and signs of
HF in a patient showing preserved LV ejection fraction (LVEF) and
no valvular disease. Also, the echocardiogram showing apical
obliteration of one or both ventricles with a hyperrefringent apex and
atrial dilation were used as entry criteria for EMF, as previously
demonstrated.4 The exclusion criteria were creatine clearance ⬍30
mL/min, relative or absolute contraindications to CMR studies, and
the presence of other systemic or cardiac diseases.
We prospectively studied 36 patients (29 women; age, 27 to 77
years, 54⫾12 years) with diastolic HF diagnosis followed at outpatient cardiomyopathy clinic. A detailed clinical history, physical
examination, complete blood count including eosinophil count, and
comprehensive 2-dimensional Doppler echocardiography were carried out, resulting in a diagnosis of EMF. The patients then
underwent cine-CMR and LGE- CMR to fully detect and quantify
the FT deposition.
The EMF patients were classified on the basis of location of
LGE-CMR and were divided into the following subgroups: LV-FT
for patients with fibrosis in the LV; RV-FT for patients with fibrosis
in the RV; and Bi-FT, for patients with fibrosis in both ventricles.
Minimal amounts of scattered or punctuate fibrosis detected by
LGE-CMR in the contralateral ventricle were not considered in this
classification and could not be added to the FT volume.
Control and Hypertrophy Groups
To evaluate the diagnostic performance of LGE-CMR in EMF
patients, we compared the results obtained in this patient population
with those acquired from 10 healthy volunteers (all men; age, 44⫾8
years; all with normal ECGs and echocardiograms; control group)
and 15 patients with LV hypertrophy (9 men; age, 37⫾16 years; all
with hypertrophic cardiomyopathy, including 2 apical forms; with
LV hypertrophy on ECG and echocardiography; LVH group).
Patients with confirmed EMF were treated with standard HF
pharmacological therapy. Warfarin was used if permanent atrial
fibrillation or previous thromboembolic events were present. Patients
remaining in NYHA functional classes III and IV after medical
therapy were offered surgical resection.3 The surgical specimens
Magnetic Resonance in Endomyocardial Fibrosis
305
were processed for histopathologic analyses. The study was approved by our institutional review board, and informed consent was
obtained from all study subjects.
CMR Imaging Protocol
CMR studies were performed with a 1.5-T magnet (General Electric
Medical Systems, SIGNA, CV/I, Waukesha, MN) using a cardiac
phased-array surface coil. The cardiac images were obtained during
breath-holding for 12 to 15 cardiac beats (10 to 15 seconds on
average) at the end of the expiration, synchronized with the ECG.
Two specific pulse sequences were used: cine-CMR with the
steady-state free precession technique (SSFP) and LGE. Initially, the
first images were acquired to evaluate the correct position of
the cardiac coil and to define the short- and long-axis views of the
LV. To cover the LV from apex to base, 8 to12 short-axis slices of
8-mm thickness at 2-mm intervals were acquired. The long axis was
perpendicular to the short axis, and both axis slices were acquired
with the 2 pulse sequences, as previously described. The cine-CMR
using the SSFP technique was performed to evaluate ventricular
morphology, volumes, ejection fraction, and mass and was used for
the following parameters: field of view, 34 to 38 cm; matrix,
256⫻160; receiver bandwidth, 125 kHz; k-space segmented, 8 to 12
lines; TR, 3.9 ms; TE, 1.4 ms; flip angle, 45°; 3/4 field of view;
number of excitations equal to 1; and 20 phases for each cardiac
cycle. Patients received an intravenous bolus of 0.2 mmol/kg of
gadolinium-based contrast. Ten to 20 minutes after gadolinium
injection, images were acquired by using the LGE technique, which
is a gradient-echo pulse sequence with an inversion-recovery preparatory pulse.11 The parameters used were TR, 7.2 ms; TE, 3.2 ms;
matrix, 256⫻192; flip angle, 20°; bandwidth, 31.2 kHz; inversion
time, 150 to 300 ms; number of excitations equal to 2; and
acquisition in every heart beat (1 RR).15 After contrast, the inversion
time was adjusted to null the signal from normal myocardium (dark
myocardium) and clearly shows the FT region as intensely bright.
Image Analysis
The LV and RV volumes and derived stroke volume and EF were
obtained by the detection of endocardial and epicardial contours of
all short-axis slices at end-diastole and end-systole and application of
the Simpson method. Biventricular mass was calculated with Mass
Analysis Plus software (MEDIS, Medical Imaging Systems, Leiden,
The Netherlands) and corrected by body surface area (BSA).
The FT volume was calculated as a sum of the component
volumes derived by planimetry of the 8 to 12 slices obtained from the
short-axis view from apex to base at end-diastole (mL/m2) in each
ventricle (FT-LV or FT-RV), and indexed by body size (FT/BSA). In
the case of biventricular EMF, the FT of each ventricle was
combined and corrected by BSA (FT-Bi). FT mass (g/m2) was
calculated by the FT volume multiplied by the specific density of
myocardium (1.05 g/cm2) and corrected by BSA. The cine SSFP and
LGE images were analyzed by 2 cardiologists with extensive
experience in interpreting MRI and LGE in several clinical situations, with a deep knowledge of the pulse sequence, its pitfalls, and
artifacts. When disagreement between the 2 observers occurred, the
final decision was made by consensus.
Histopathologic Analysis
Sixteen patients underwent surgical resection of the FT. The excised
tissue obtained from 14 patients was fixed in formalin, underwent
decalcification if necessary, and embedded in paraffin. Four-micrometer-thin sections were stained with hematoxylin and eosin and
Masson trichrome and analyzed under light microscopy.
Statistical Analysis
All data are expressed as mean⫾SD or frequency (%) for discrete
variables. The likelihood ratio test or ␹2 test was used to compare
EMF groups for sex, NYHA functional class, cardiac rhythm, and
mortality. The Pearson correlation coefficient was used to analyze
the relation between RV and LV FT/BSA with RV and LVmass/
BSA, respectively. Comparisons of normally distributed continuous
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May 2011
Figure 1. Preoperative late gadolinium enhancement CMR of 5 patients with EMF shows the typical pattern of RV EMF (A), LV EMF (B), LV EMF
with dark areas representing thrombus formation
or calcification (C), and biventricular EMF (D).
Histopathologic analysis (E) of the resected
endomyocardium, from the same patient seen in
D, shows severe fibrous thickening of the endocardium (End) that penetrates the myocardium
(Myoc); note proliferated small vessels and scarce
inflammatory infiltrate in the endocardium.
Bar⫽500 ␮m; LV EMF with dark areas represent
thrombus formation or calcification (F).
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variables were performed with the t test and 1-way ANOVA with
Bonferroni adjustments for multiple comparisons. The t test was
used to compare surgical or clinical treatment and FT/BSA. Cutoff
value was determined on the basis of receiver operating characteristic curve, which was generated by logistic regression. The Kaplan–
Meier method was used for survival curves, with the log-rank test
with a mean RV mass of 22 g/m2 and FT/BSA of 19 mL/m2 used as
the cutoff value. The significant variables were adjusted in the
multivariate analysis model by Cox regression. The covariates that
were candidates for entry in multivariate model were BSA
(P⫽0.044), RV mass/BSA (P⫽0.011), and FT/BSA (P⫽0.001). The
significance level predictor to enter the model was 0.05 and to be
eliminated from it was 0.10. Normality was determined by the
Shapiro-Wilk test. Two-sided P⬍0.05 was considered statistically
significant. Statistical analysis was performed with SPSS v 15 (SPSS
Inc, Chicago, IL).
Results
The typical EMF image observed consisted of areas of LGE in
the endocardium, mainly in the apex and eventually in the inflow
tract of one or both ventricles, frequently as continuous stria,
with preservation of both outflow tract orifices and not confined
to coronary territory. The CMR LGE pattern had a “V sign” at
the ventricular apex, characterized by a 3-layer appearance of
myocardium, thickened fibrotic endomyocardium, and overlying
thrombus. Typical LGE-CMR images are shown in Figure 1,
and cine-CMR of EMF and hypertrophic cardiomyopathy patients are shown in Figure 2 and video 1 (online-only Data
Supplement). Clinical characteristics and CMR values from
EMF patients are shown in Table 1.
Figure 2. Four-chamber, long-axis CMR shows LV
apical obliteration (upper left), RV (upper right),
biventricular (lower left) by endomyocardial fibrosis, and CMR of a patient with hypertrophic cardiomyopathy (lower right) showing the classic
spade-shaped ventricular cavity in systole for
comparison.
Salemi et al
Magnetic Resonance in Endomyocardial Fibrosis
307
Table 1. Clinical and Cardiovascular Magnetic Resonance Characteristics of Endomyocardial
Fibrosis Patients
Variable
All (n⫽36)
RV-FT (n⫽7)
Bi-FT (n⫽12)
P Value
Age, y
54⫾12
56⫾15
55⫾10
Female
29 (81%)
4 (57%)
14 (82%)
11 (92%)
0.204‡
56%
71%
29%
83%
0.008‡
1.6⫾0.2
1.7⫾0.1
1.6⫾0.2
1.6⫾0.1
0.281*
36%
71%
12%
50%
0.008‡
58⫾12
57⫾13
58⫾9
58⫾15
0.981*
NYHA class, III/IV
BSA, m2
Atrial fibrillation
LVEF, %
LV mass/BSA, g/m2
46⫾8
LV-FT (n⫽17)
0.188*
68⫾21
61⫾13
72⫾24
66⫾19
0.493*
2
LVd vol/BSA, mL/m
57⫾15
51⫾15
60⫾15
55⫾15
0.349*
LVs vol/BSA, mL/m2
24⫾10
22⫾7
26⫾10
23⫾11
0.497*
LV stroke volume, mL
33⫾10
30⫾12
34⫾8
32⫾13
0.610*
RVEF, %
46⫾13
59⫾14†
43⫾11
43⫾13
0.016*†
2
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RV mass/BSA, g/m
20⫾6
25⫾8
18⫾5†
22⫾4
0.014*†
RVd vol/BSA, mL/m2
56⫾20
46⫾18
60⫾22
55⫾17
0.325*
RVs vol/BSA, mL/m2
31⫾15
20⫾10
35⫾18
31⫾9
0.071*
FT/BSA, mL/m2
15⫾9
13⫾9
10⫾5
22⫾9†
⬍0.001*†
FT mass/BSA, g/m2
15⫾10
14⫾9
10⫾5
25⫾8†
⬍0.001*†
Surgery
44%
57%
29%
58%
0.223‡
Death
22%
29%
6%
42%
0.054‡
LVd vol indicates LV end-diastolic volume; LVs vol, LV end-systolic volume; RVd vol, RV end-diastolic volume; and
RVs vol, RV end-systolic volume.
Data are expressed as mean⫾SD or n (%) for discrete variables.
*One-way ANOVA.
†Bonferroni adjustments for multiple comparisons were done on the variables that presented P⬍0.05 (ANOVA) and
showed difference from other EMF groups (P⬍0.05).
‡Likelihood ratio test.
All patients presented apical areas of LGE, 17 in the LV
(47%, LV-FT), 7 in the RV (20%, RV-FT), and 12 in both
ventricles (33%, Bi-FT) (Table 1). The FT/BSA and FT
mass/BSA were 10⫾5 mL/m2 and 10⫾5 g/m2 in LV-FT,
13⫾9 mL/m2 and 14⫾9 g/m2 in RV-FT, and 22⫾9 mL/m2
and 25⫾8 g/m2 in Bi-FT, with greater Bi-FT volume and
Bi-FT mass (P⬍0.001).
In our study group of 36 patients, we considered the
comprehensive echocardiogram for the diagnosis criteria of
EMF. On a retrospective analysis, we found that 9 of the total
36 patients had had their first echocardiogram with findings
that differed from the final EMF diagnosis. The initial
diagnoses were normal (n⫽3), mitral valvulopathy (n⫽2),
dilated cardiomyopathy (n⫽1), suspected Ebstein anomaly
(n⫽1), apical hypertrophic cardiomyopathy (n⫽1), and pulmonary hypertension (n⫽1).
The EMF subgroups were similar in age, sex, BSA, LVEF,
LV mass, stroke volume, and LV and RV volumes (Table 1).
Figure 3. Relation between FT volume/
BSA and NYHA functional class (FC).
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Figure 4. Relation of FT volume/BSA and clinical and surgical
patients.
Of the 36 patients with EMF, 20 were in NYHA functional
classes III and IV (Figure 3). Atrial fibrillation was less
common in the LV-FT.
The RV-FT subgroup had higher RVEF compared with
those in the LV-FT and Bi-FT subgroups (59⫾14%,
43⫾11%, and 43⫾13%, respectively; P⫽0.016). Although
LV mass/BSA was not different among groups, RV mass/
BSA was reduced in the LV-FT subgroup (Table 1). RV-FT
and Bi-FT subgroups had a higher percentage of patients in
NYHA functional class III/IV (71% and 83%, respectively)
than did the LV-FT (29%; P⫽0.008).
On a retrospective evaluation, greater FT/BSA was found to
correspond to a worse NYHA functional class and higher
likelihood of surgery (Figure 3 and Figure 4). RV FT/BSA
correlated positively with RV mass/BSA (r⫽0.773; P⬍0.001).
Cutoff values were determined by using the receiver operating
characteristic curve and showed that patients with RV mass/
BSA ⬎22 g/m2 and FT/BSA ⬎19 mL/m2 had worse survival
rates (Figure 5). In multivariate analysis, FT/BSA was the only
independent predictor of mortality, with a relative risk of 10.8
and 95% confidence interval of 2.10 to 55.39 (Figure 6, Table 2).
FT resection was indicated in 20 patients with NYHA
functional classes III and IV. Four of these patients refused
surgery. Of the 16 patients who underwent surgical resection,
5 died in the first year after surgery and 1 died 3 years after
surgery. Two other deaths occurred in the clinical therapy
group: One was a patient who had refused surgery and the
other was from the clinically treated group. All deaths were
from cardiac causes (4 patients with sudden cardiac death and
4 patients from worsening HF). There was a tendency for
fewer surgical procedures and lower mortality rates in the
LV-FT subgroup (Table 1).
Figure 5. Mortality receiver operating characteristic curve of RV
mass/BSA and FT volume/BSA.
myocardium. The EMF group of 15 patients (100%) had
areas of LGE in the endocardium, mainly in the apex and
eventually in the inflow tract of one or both ventricles,
frequently appearing as continuous stria. A correct diagnosis
was reached by a consensus of the examiners in all but 1 case,
diagnosed as normal when the patient had mild LVH.
Eosinophil Count
Eosinophil counts were ⬍1500/mm3, except in 1 patient
(1786/mm3).
Histology
Of the 16 surgical cases, pathological data were not available
in 2 cases. The remaining 14 cases had histological features
typical of EMF. Extensive endocardial fibrous thickening
irregularly penetrated the subendocardial myocardium. Additionally, small-vessel proliferation and mild-to-moderate inflammatory infiltrate with scarce eosinophils were present in
the endocardium (Figure 1). Fibrosis was present in all
specimens; superficial thrombosis was present in 9 of 14
LGE-CMR in Control, Hypertrophy, and
EMF Groups
The frequency and/or pattern of LGE in the 3 groups were as
follows: in the control group of 10 individuals, no LGE; in the
hypertrophy group of 15 patients, 4 LGE (27%), showing
small spotty areas of fibrosis limited to the mid layers of the
Figure 6. Worse survival rate in patients with RV mass/BSA
⬎22 g/m2 and FT volume/BSA ⬎19 mL/m2.
Salemi et al
Table 2.
Magnetic Resonance in Endomyocardial Fibrosis
309
Results of Multivariate Cox Regression
Cox Regression
Variable
FT/BSA, ⬎19 mL/m2
Estimated
Parameter
Standard
Error
P
Relative
Risk
2.38
0.83
0.004
10.79
(64%) cases and calcification was present in 6 of 14 (43%)
cases.
Discussion
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The utility of LGE in the diagnosis of EMF has been limited
to a few case reports.14,16,17 The present study demonstrates
the typical LGE-CMR in a relatively large number of patients
with EMF on echocardiography. In addition, the histological
analysis confirmed the LGE-CMR diagnosis in all 14 patients
who underwent surgical FT resection.
In all patients, LGE regions were observed only in the
endocardium, appearing as a continuous area, commonly
extending from the subvalvar region to the apex of the
ventricles, where it was usually more prominent. Also, a
3-layered appearance (V sign at the apex) was typical of this
disease with an inner layer showing no perfusion due to
presence of thrombus, a middle layer of LGE reflecting the
FT and an outer layer of almost normal myocardium. In our
surgical subgroup, all EMF diagnosed by LGE-CMR was
confirmed by histopathology. These data suggest that
LGE-MR may play a role in EMF diagnosis.
The patients’ first echocardiography report differed from
the final EMF diagnosis in 9 patients. Considering the low
prevalence of EMF in the population, an inexperienced
examiner may miss the EMF diagnosis. This might suggest
that in the event of suspected EMF, apical hypertrophy, or
restrictive cardiomyopathy with apical filling, an LGE-CMR
study might help in defining the correct diagnosis by delineating clearly the morphology of the apex and characterizing
the FT.
RV involvement evaluated invasively by ventricular angiography is a predictor of a worse prognosis in EMF
patients.9 Tissue characterization obtained with LGE-CMR
allows for a critical evaluation of the fibrotic deposition
occurring in the right ventricle. The RV-FT subgroup had
higher RVEF compared with the other groups; probably the
small RV cavity in these patients is the main factor leading to
a higher EF.
Previous studies demonstrated that atrial fibrillation is a
marker of a worse prognosis in this disease18 and that RV-FT
and Bi-FT subgroups have a poorer evolution.9 In our study,
RV-FT and Bi-FT subgroups presented a higher incidence of
atrial fibrillation, which might indicate that this arrhythmia
may be a contributing factor of worse prognosis in these
subgroups.
CMR allowed the noninvasive quantification of cardiac
volumes. A noteworthy finding is the significantly reduced
LV stroke volumes (33⫾10 mL) in all patients and subgroups
compared with the normal range (104⫾21 mL),19 which,
associated with preserved LVEF, is typical of restrictive
cardiomyopathy.
95% Confidence
Interval
2.10
55.39
Endomyocardial Biopsy and LGE-CMR in EMF
In some institutions, RV endomyocardial biopsy is part of the
EMF diagnostic workup, providing the diagnosis and excluding other restrictive cardiomyopathies, particularly infiltrative
and storage diseases. However, it has been previously demonstrated that endomyocardial biopsy allows the diagnosis in
only about 50% of patients.10 Our data indicate that a biopsy
may not be required for establishing the diagnosis of EMF if
a LGE-CMR study provides reliable evidence based on
criteria we describe here. We also propose LGE-CMR as the
best noninvasive method for diagnosing EMF.
Eosinophils, Thrombus, and Calcification
A high eosinophil count may be found in the initial stages of
the disease.1 Our patients, who had normal or mild elevation
of eosinophil counts, probably were in the later fibrotic phase of
the disease, as corroborated by the histopathologic analysis of
surgical specimens showing a low number of inflammatory
cells. Although it has not been already demonstrated, we
speculate that earlier endomyocardial alterations, such as the
initial inflammatory process, may be detected with LGECMR performed at the initial stage of the disease. The
presence of thrombus may be detected by LGE-CMR as
regions with a dark appearance surrounded by bright contrastenhanced blood.20 With LGE-CMR, we observed the presence of these dark-appearing regions. Areas of calcification,
which were found in the histological analysis, are difficult to
distinguish from thrombus on the basis of LGE images only
(with the same dark appearance). However, CMR can differentiate thrombus from calcification because the acute thrombus that will appear bright on both T1- and T2-weighted
images and subacute thrombus that will be bright on T1 and
with a low signal on T2, due to the paramagnetic effect of
methemoglobin and shortening of T2 relaxation times.21
Chronic organized thrombus has low signal intensity on both
T1 and T2 images as the result of decreased water content
and/or concomitant calcification and might be more difficult
to differentiate from calcification alone.22 The specific techniques described above were not performed in our study.
Differentiating EMF From Other
Cardiomyopathies Using LGE-CMR
FT deposition is also a frequent finding in Chagas disease,
with a heterogeneous midwall and subepicardial distribution
preferably in the apex and basal inferolateral segments,
although it can appear in a pattern indistinguishable from
alterations found in coronary artery disease.15 This pattern of
FT distribution and appearance is clearly distinct from the
homogeneous and exclusively endomyocardial distribution
found in our EMF patient study population. In EMF patients,
the apical systolic inward motion is commonly preserved,23
differing from the dyskinetic motion of thrombotic apical
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obliteration occurring in patients with coronary artery disease
or Chagas disease.12
Other conditions, such as amyloidosis, sarcoidosis, and
subendocardial infarction, could cause subendocardial
LGE.12 The most important aspect that clearly differentiates
EMF from other causes is that the LGE is subendocardial but
on top of an apical filling mass and frequently extends to the
inflow tract involving subvalvar apparatus. LGE in EMF is
also heterogeneous with hypointense areas that can be associated with thrombus or calcification. In subendocardial
infarction, however, the LGE is related to a coronary artery
distribution, there is no apical filling mass, and when involving the apex is usually associated with wall thinning and wall
motion abnormality. LGE in cardiac amyloidosis often demonstrates global, inhomogeneous, subendocardial hyperenhancement associated with a global increase in wall thickness
and systolic dysfunction. LGE in sarcoidosis will appear as
areas of myocardial enhancement in regions with granulomas.
These areas often show wall thinning and wall motion
abnormalities. They are usually located in the septum but can
affect other walls, with midwall, epicardial, or transmural
involvement, whereas papillary muscle and the RV wall are
rarely affected. In LV noncompaction, thickened apical segments of the myocardium have a double-layered appearance
with marked trabeculations and deep intratrabecular recesses
located in the mid and apical portions of the ventricle.
Nontransmural LGE of the prominent trabeculations suggesting areas of fibrosis is more frequent than transmural LGE.12
LGE-MRI and Surgery in EMF Patients
Surgical resection of FT is the recommended treatment for
patients in NYHA functional classes III and IV.24,25 The FT
distribution and localization obtained with LGE-CMR may
contribute to surgical planning, offering anatomic details that
may guide the surgical procedure. In particular, the extent of
apical calcification may be of special interest, leading the
surgeon to choose a different approach. The increased mortality rate observed in patients with FT/BSA ⬎19 mL/m2 may
be related to the severity of LV filling restriction and to the
irreversible myocardial damage triggering arrhythmic events.
The follow-up assessment of the quantification of FT by
LGE-CMR, including after surgery, may contribute to a
better understanding of the disease progression and
recurrence.26
Conclusions
Our study provides evidence that LGE-CMR is useful in the
diagnosis of EMF by characterization of FT distribution,
which is the hallmark of the disease. A consistent pattern of
LGE was observed, with FT present only in the subendocardium, appearing as a continuous area, commonly extending
from the subvalvar region to the apex of the ventricles, where
it was usually more prominent. Morphological and tissue
characterization by LGE-CMR leads to a confident diagnosis
of EMF. Our initial data suggest that parameters evaluated by
CMR, such as FT/BSA, can convey prognostic information.
Acknowledgment
We thank Julia T. Fukushima for the statistical work and review.
Disclosures
None.
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CLINICAL PERSPECTIVE
We evaluated the role of late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) for the diagnosis
of endomyocardial fibrosis (EMF) using surgical specimens as the standard method. LGE-CMR confirmed the diagnoses
of EMF patients on the basis of areas of LGE that were confined to the endocardium as continuous stria from the inflow
tract to the apex. Histopathology of fibrous tissue in 14 patients showed typical features of EMF. Our study provides
evidence that LGE-CMR is a reliable diagnostic tool to confirm EMF.
Downloaded from http://circimaging.ahajournals.org/ by guest on May 10, 2017
Late Gadolinium Enhancement Magnetic Resonance Imaging in the Diagnosis and
Prognosis of Endomyocardial Fibrosis Patients
Vera M.C. Salemi, Carlos E. Rochitte, Afonso A. Shiozaki, Joalbo M. Andrade, José R. Parga,
Luiz F. de Ávila, Luiz A. Benvenuti, Ismar N. Cestari, Michael H. Picard, Raymond J. Kim and
Charles Mady
Downloaded from http://circimaging.ahajournals.org/ by guest on May 10, 2017
Circ Cardiovasc Imaging. 2011;4:304-311; originally published online March 17, 2011;
doi: 10.1161/CIRCIMAGING.110.950675
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Supplemental Material
Video. Four-chamber, long-axis, cine-CMR showing left ventricular apical obliteration (upper
left), right ventricular (upper right), biventricular (lower left) by endomyocardial fibrosis and
cine-CMR of a patient with hypertrophic cardiomyopathy (lower right) showing the classic spadeshaped ventricular cavity in systole for comparison.