DOI: 10.1111/echo.

13367

CHALLENGING CASES

Differential diagnosis of left ventricular hypertrophy:

usefulness of multimodality imaging and tissue
characterization with cardiac magnetic resonance

Cemil Izgi M.D.1,2 | Vassilis Vassiliou M.D.1,2 | A. John Baksi M.B.B.S., Ph.D.1,2 | 

Sanjay K. Prasad M.D.1,2

1
Cardiovascular MR Unit, Royal Brompton
Hospital, London, United Kingdom
2
NIHR Cardiovascular Biomedical Research
Unit, Royal Brompton Hospital, London,
United Kingdom
Correspondence
Cemil Izgi, Cardiovascular MR Unit,
Royal Brompton Hospital, London,
United Kingdom.
Email: C.Izgi@rbht.nhs.uk
Differential diagnosis of asymmetrical left ventricular hypertrophy may be challenging,
particularly in patients with history of hypertension. A middle-­aged man underwent an
echocardiographic examination during workup for hypertension, which unexpectedly
showed significant asymmetrical septal hypertrophy and raised suspicion for hyper-
trophic cardiomyopathy. Cardiovascular magnetic resonance confirmed the asymmet-
rical hypertrophy. No myocardial late gadolinium contrast enhancement was seen.
However, precontrast T1 mapping revealed a low native myocardial T1 value. This was
highly suggestive of Anderson-­Fabry disease, which was subsequently proved with
very low alpha galactosidase enzyme levels and mutation analysis. The case illustrates
clinical usefulness of multimodality imaging and the novel tissue characterization
­techniques for assessment of left ventricular hypertrophy.

KEYWORDS
Anderson-Fabry disease, cardiac magnetic resonance imaging, echocardiography, hypertrophic
cardiomyopathy, left ventricular hypertrophy

1 |  CASE HISTORY thickness of 22 mm at the mid-­inferoseptum (Fig. 3). However, no

A 46-year-­old man with a history of hypertension was referred for an
echocardiographic examination when his ECG revealed left ventric-
ular (LV) strain pattern suggestive of LV hypertrophy (Fig. 1). Apart
from hypertension, he did not have any significant medical history
or family history. Substantiating the ECG findings, echocardiogra-
phy showed LV hypertrophy in asymmetric distribution and mainly
involving the septum (septal wall thickness 20 mm and inferolateral
wall thickness 12 mm) (Fig. 2). LV ejection fraction was normal at
70%. No LV outflow obstruction was seen. A preliminary diagno-
sis of hypertrophic cardiomyopathy was made while considering
hypertensive heart disease, Anderson-­Fabry disease, and cardiac
amyloidosis in the differential diagnosis. The patient was referred
for cardiovascular magnetic resonance (CMR) for further assess-
ment. CMR examination confirmed the echocardiographic findings
showing asymmetrical LV septal hypertrophy with maximum wall
regions of myocardial enhancement were seen in the late phase fol-
lowing gadolinium administration to suggest replacement fibrosis.
Myocardial T1 mapping had also been performed before gadolin-
ium administration and native myocardial T1 from the septum was
measured as 880 ms (normal range in controls is 975–1065 ms in
the same scanner settings). The low native myocardial T1 was typ-
ical of Anderson-­Fabry disease with normal or increased values
seen in the other aetiologies initially considered in the differential
diagnosis. Subsequent testing of the patient for plasma alpha galac-
tosidase activity revealed very low levels (0.2 nmol/h/mL, normal:
4.0–21.9 nmol/h/mL) along with genetic analysis showing hemizy-
gous N215S mutation confirming the diagnosis of Anderson-­Fabry
disease. Kidney function was normal and there were no cutaneous
lesions suggesting predominant cardiac involvement. The patient
was started on alpha galactosidase enzyme replacement therapy,
and family screening was advocated.

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1766       Izgi et al.
2 |  DISCUSSION
On the background of hypertension and with the significant asym-
metrical LV hypertrophy, the possible diagnosis considered in this pa-
tient was hypertrophic cardiomyopathy, hypertensive heart disease,
Anderson-­Fabry disease, and cardiac amyloidosis. However, the mor-
phological features of the hypertrophy alone were not sufficient to
discriminate between these etiologies. Tissue characterization could
provide additional diagnostic information. Tissue characterization
with echocardiography is limited and possible clues for the etiology
in this case would be septal speckling pattern suggestive of amyloido-
sis and the binary appearance of the myocardium with a hyperecho-
genic endocardial layer suggestive of Anderson-­Fabry disease, both
of which were absent in the presented case. In the setting of car-
diomyopathies, tissue characterization with CMR has conventionally
been performed with the late gadolinium enhancement study, which
is now an established technique and can shed light on the etiology
by revealing typical patterns of late enhancement.1 In patients with
left ventricular hypertrophy, presence and location of any replace-
ment fibrosis or any evidence for infiltration in late gadolinium images
will be helpful in assessing the etiology.1 Patchy mid-­wall fibrosis in
hypertrophied segments is typical of hypertrophic cardiomyopathy;
however, this finding might be absent in up to 30% of the patients.1 A
F I G U R E   1   ECG of the patient showing
signs suggestive of LV hypertrophy such as
tall R-­waves in leads I and aVL along with
ST changes in lateral leads
F I G U R E   2   Parasternal long-­axis (A) and
apical four-­chamber (B) echocardiographic
views showing septal LV hypertrophy
(septal thickness 20 mm). LV=left ventricle;
RV=right ventricle; Ao: aorta
basal inferolateral mid-­wall fibrosis is suggestive of Anderson-­Fabry
disease. The typical pattern in amyloidosis is altered gadolinium kinet-
ics resulting in dark blood pool and diffuse myocardial enhancement.
Hypertensive heart disease will mostly cause more concentric hyper-
trophy and replacement fibrosis is less likely to be present. In the pre-
sented case, gadolinium contrast kinetics were normal and there were
no regions of late gadolinium enhancement. Moreover, the degree of
asymmetry was more than one would expect for hypertensive heart
disease.
T1 mapping has recently emerged as a valuable tool for myo-
cardial tissue characterization including assessment of extracellular
volume fraction as a surrogate measure of interstitial fibrosis. In the
case of LV hypertrophy, myocardial native T1 has been shown to
be significantly lower in cases with Anderson-­Fabry disease proba-
bly reflecting accumulation of glycosphingolipid in the myocardium,
as the T1 of fat is very low.2 Sado et al.3 showed that in patients
with common causes of LV hypertrophy, those with Anderson-­Fabry
disease had lower T1 values when compared to all other aetiolo-
gies of LV hypertrophy and controls without any overlap and hence
providing full discrimination of the cases with Anderson-­Fabry dis-
ease. Figure 4 shows parametric native T1 map of the presented
case and a representative case of hypertrophic cardiomyopathy for
comparison. Septal native T1 of the patient was lower than normal
Izgi et al. |
      1767

F I G U R E   3   CMR images. Four-­

chamber end-­diastolic (A) and end-­
systolic (B) images showing asymmetrical
LV hypertrophy with systolic cavity
obliteration and an ejection fraction of
70%. the LV mass was increased at 220 g.
Mid-­cavity short-­axis end-­diastolic cine
frame (C) and the late gadolinium image
(D) revealing max wall thickness of 22 mm
in the inferoseptum and absence of any
regions of late gadolinium enhancement.
LV=left ventricle; RV=right ventricle;
LA=left atrium; RA=right atrium

F I G U R E   4   Top row are images of the

presented case and the bottom row are
images from a known case of sarcomeric
hypertrophic cardiomyopathy with
maximum septal thickness of 21 mm for
comparison. A, C. are end-­diastolic mid
short-­axis cine frames, and (B) and (D)
are parametric native T1 maps acquired
with the modified Look Locker inversion
recovery (MOLLI, Siemens 448B) sequence
at 1.5T. Note that overall myocardial T1 is
lower in this patient with LV hypertrophy
secondary to Anderson-­Fabry disease
than the patient with hypertrophic
cardiomyopathy allowing differentiation
of these two pathologies as previously
shown by Sado et al.3 LV=left ventricle;
RV=right ventricle; arrows pointing to the
corresponding T1 value in the color-­coded
scale
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1768       Izgi et al.
range; with a low T1 value, a diagnosis of Anderson-­Fabry disease
with cardiac involvement was considered highly likely which was
later confirmed by enzyme and genetic analysis. Of note, the endo-
cardial hyperechogenicity on echocardiography and the inferolateral
mid-­wall fibrosis on CMR, which were previously suggested to be
2,4
sensitive imaging markers for Anderson-­Fabry disease, were not
present in this patient.
This case highlights the additional diagnostic yield of T1 map-
ping in a patient with LV hypertrophy to reach the correct diagnosis
which led to an important change in the management. Up to 50%
of patients with Anderson-­Fabry disease may have uncontrolled
hypertension5 and up to 5% of patients referred with a hypertro-
phic cardiomyopathy diagnosis may actually have Anderson-­Fabry
disease.2 Native myocardial T1 mapping allows accurate diagnosis
of LV hypertrophy secondary to Anderson-­Fabry disease.3 The ro-
bustness of the T1 mapping technique even allows identification
of rare cases of combined sarcomeric hypertrophic cardiomyopa-
thy and Anderson-­Fabry disease.6 The importance of correct and
early diagnosis is vital as a specific enzyme replacement therapy
is available.
ACKNOWLE DG ME NTS
This work was supported by NIHR Cardiovascular Biomedical
Research Unit of Royal Brompton & Harefield NHS Foundation Trust
and Imperial College London.
CO NFL I C T O F I NT ER ES T
The authors declare that they have no competing interest.
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How to cite this article: Izgi, C., Vassiliou, V., Baksi, A. J. and
Prasad, S. K. (2016), Differential diagnosis of left ventricular
hypertrophy: usefulness of multimodality imaging and tissue
characterization with cardiac magnetic resonance.
Echocardiography, 33: 1765–1768. doi: 10.1111/echo.13367