CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 1, January/February 2011
42
AFRICA
in LVH by echocardiography
31,66
and CMR.
67,68
Hughes
et al
.
also document a 20% reduction in myocardial Gb
3
content by
cardiac biopsy at six months of therapy, versus a 10% increase in
patients receiving placebo.
68
At least one study has documented
an improvement in diastolic dysfunction (29% decrease of E/Ea;
p
<
0.002), although there was no improvement in LVH or renal
function.
69
However, at two years, one study has shown no statis-
tically significant changes on ECG, stress echocardiography or
CMR, although one-year follow-up data did look promising.
70
Although improvement in symptoms of CHF and angina have
been reported as improved with therapy,
31
this remains open
to question.
70
The lack of efficacy may be due to the degree
of fibrosis. As hypothesised previously,
48
a recent case-control
study found a statistically significant reduction in LVH (
p
<
0.001), improved myocardial function by TDI (
p
=
0.045) and
improved exercise capacity (
p
=
0.014) in patients with no fibro-
sis by late gadolinium enhancement at three years. However, in
patients with mild or severe fibrosis, there was only minimal
improvement in LVH and no improvement in LV function or
exercise capacity.
71
Angina and arrhythmias
Interestingly, in one series, conduction and valvular abnormali-
ties were more common in patients receiving treatment, most
likely reflecting the biases of observational studies.
31
Overall,
there is little data on the incidence/prevalence of arrhythmias
with and without treatment, however one author reports on the
lengthening of an ‘abbreviated PR interval’ in one patient.
72
Coronary microvascular dysfunction does not appear to improve
on therapy,
73,74
nor does angina improve despite improvement
in LVH,
70,73
however, this may be confounded by the degree of
cardiac involvement (see above). Regardless, this does imply that
angina may be more related to microvascular dysfunction than
to hypertrophy and supply–demand mismatch of oxygenation.
Conventional therapy
Fabry’s patients with obstructive coronary artery disease should
be managed as any other patient, including treatment with aspi-
rin, lipid-lowering therapy, anti-anginals, beta-blockers, etc, and
revascularisation should be according to the standard of care.
75
However, special considerations with regard to coronary artery
bypass grafting may be warranted. One case report has suggested
that at least in untreated Fabry’s patients, vein grafts may be
better conduit vessels than the left internal mammary artery
due to an increased amount of sphingolipid infiltration, thus
making arterial conduits more susceptible to premature failure.
76
Significant valvular disease should be managed per the current
guidelines,
77
and case reports of both aortic
78
and mitral
79
valve
replacements have been documented. Pacemaker for symptomat-
ic bradycardia, heart block, etc. should be implanted according to
current device guidelines.
80
Medical therapy for Fabry’s patients with systolic dysfunction
should include: angiotensin-converting enzyme inhibitor (ACEI)
or aldosterone receptor blocker (ARB), beta-blocker, hydrala-
zine plus nitrate in patients of African descent after maximal
titration of ACEI or ARB, and diuretics for volume manage-
ment. Furthermore, ICD and biventricular pacing should also
be considered after maximal medical therapy as per guidelines.
81
Diastolic dysfunction should be treated with diuretics for symp-
tom management, although there is some retrospective data that
statins may improve mortality.
82
Symptomatic Fabry’s cardiomyopathy mimicking hypertroph-
ic obstructive cardiomyopathy may benefit from septal alcohol
ablation.
83
Fabry’s patients with end-stage heart failure on maxi-
mal medical therapy should also be considered for transplant
regardless of the aetiology.
84
Interestingly, the transplanted organ
would also produce alpha-galactosidase A, possibly protecting
from future cardiac abnormalities due to glycosphingolipid
accumulation.
Based on limited data from small studies, it appears that treat-
ment should be initiated early, ideally before the development of
fibrosis (late enhancement on CMR).
71
However, ERT does not
replace conventional medical therapy for arrhythmias, angina
and heart failure.
Conclusion
Although Fabry’s disease in the general population is rare, it may
be relatively common in patient’s presenting with late cardiac
hypertrophy. Cardiac involvement in both the classical and cardi-
ac variant, Fabry’s disease is characterised by arrhythmias and
LV hypertrophy. The hypertrophy in Fabry’s cardiomyopathy can
potentially be distinguished from other aetiologies by TDI when
isovolumic contraction time is
≤
105 ms and Ea is < 10 cm/s,
and by expert interpretation of late gadolinium enhancement and
prolonged T2 relaxation time on cardiac MRI. TDI may also be
able to detect cardiac involvement before the development of
hypertrophy.
Treatment with enzyme replacement therapy may decrease
the frequency of cardiac events, decrease hypertrophy, and, if
started early before the development of fibrosis, may improve
cardiac function and prevent deterioration in functional capacity.
Middle-aged patients presenting with hypertrophy, particularly
in the absence of other common aetiologies, should be evaluated
for alpha-galactosidase deficiency.
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