Cardiovascular Journal of Africa: Vol 27 No 3 (May/June 2016)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 3, May/June 2016 AFRICA 157
characteristics of HCM in Saudi Arabia, Ahmed and co-authors
found the population of HCM patients to be 71% male, and
with a mean age of 42 years.17 Dyspnoea and palpitations were
the commonest symptoms, and LVOT obstruction was found in
28%.
To date, over 1 400 mutations have been reported to cause
HCM in genes encoding eight sarcomere proteins: beta-myosin
heavy chain (MYH7 ), cardiac myosin-binding protein C
(MYPBC3), cardiac troponin T (TNNT2), cardiac troponin I
(TNNI3), cardiac actin (ACTC), alpha-tropomyosin (TPM1),
essential light chain of myosin (MYL3) and regulatory light
chain of myosin (MYL2). 15,18 Mutations in MYH7 and MYPBC3
occur most often, and account for approximately 50% of HCM
cases,19,20 while mutations in TNNT2, TNNI3, ACTC, TPM1,
MYL3 and MYL2 collectively account for less than 20% of
HCM cases.21 In our study, mutations in MYH7 and MYPBC3
were the commonest causes of HCM.
Moolman-Smook and colleagues have done pioneering work
on the genetics of HCM in two South African sub-populations:
those of European descent and those of mixed ancestry, and
have previously reported on common HCM-causing mutations
that arose independently and demonstrated clear founder effects
in the South African population. These mutations included the
MYH7 Ala797Thr (25% prevalence),8 TNNT2 Arg92Trp (15%),9
MYH7 Arg403Trp (5%),7 MYH7 Arg717Gln and the MYH7
Glu499Lys10 mutations, which collectively accounted for 47.5%
of cases of HCM from the Eastern and Western Cape provinces
of South Africa. To save money and to improve efficiency,
a strategy was proposed to first screen for these five founder
mutations before undertaking an extensive molecular genetic
screening for other HCM mutations in South Africa.10 However,
in our study of 42 South African HCM patients, these founder
mutations were absent.
The mutation yield of screening 15 sarcomeric and
non-sarcomeric genes that are associated with HCM was
relatively low in this study. Disease-causing mutations in any one
of the sarcomeric protein genes are found in up to two-thirds of
patients with HCM, and the yield of screening-associated causal
genes ranges from 40–70%.15 The indications for molecular
genetic testing in cardiomyopathy vary according to the yield of
molecular testing, the cost of molecular analyses, and the impact
of genetic testing on the medical management of the individual
and the family. Given the relatively low yield of screening in this
study, molecular genetic testing in Africans with HCM should
probably not be carried out routinely as yet, until studies on
the full spectrum of causal mutations and the impact of genetic
testing on outcome are available.
In our study, the mean duration of follow up was 9.1 years,
with an annual mortality rate of 2.9%. Complications included
heart failure, atrial fibrillation, stroke and evolution to DCM.
Myomectomy, alcohol septal ablation and heart transplantation
were performed in a small number of patients; however no
implantable cardioverter defibrillators (ICDs) were used. The
high rates of mortality observed in our study may reflect, in part,
the higher mortality rate of the South African population, as
well as the skewed nature of tertiary-centre experience with many
symptomatic patients.
In the USA, HCM was found to have an annual mortality
rate of 1.3% and to be associated with stroke, atrial fibrillation,
sudden cardiac death, congestive heart failure and the need for
heart transplantation.11 In Taiwan, HCM was reported to have
an annual mortality rate of 0.8%, and the mortality rate could
be predicted by LVOT obstruction, atrial fibrillation and female
gender.16 In Saudi Arabia, HCM had an annual mortality rate of
0.7%, with five ICDs inserted over seven years of follow up, and a
single patient progressing to end-stage dilated cardiomyopathy.17
This study has a number of important limitations. First, the
small sample size is a major weakness. This may account for
the failure to detect the effect of known predictors of mortality
in HCM, such as history of syncope and magnitude of left
ventricular hypertrophy. Second, we screened for 15 genes that
are commonly associated with HCM. However, there are several
important HCM-causing mutations in other genes that were not
included in our genetic panel, such as titin (TTN ), myosin heavy
chain gene (MYH6) and cardiac troponin C ( TNNC). Therefore,
there is a need for larger, prospective studies of HCM in Africa
that encompass all the important genetic causes of the disease.
Conclusions
We report on the first prospective investigation of the clinical
characteristics, genetics and outcome of HCM in Africans. We
found HCM to occur more in men, and with a younger age of
onset. Major symptoms and complications were similar to those
reported in North American, Middle Eastern and Asian studies.
Known and novel disease-causing mutations were identified in
the MYH7 and MYBPC3 genes, with a lower yield of mutation
screening of about 30%, compared to the expected 40–70%
found elsewhere. The mortality rate in this contemporary African
HCM series was, however, higher than reported elsewhere,
although comparable to age- and gender-matched members of
the South African population. Survival was predicted by NYHA
functional class at last visit.
We are grateful to the patients and families who participated in this study.
We acknowledge the assistance of Carolina Lemmer and Sisters Maitele
Tshifularo, Unita September and Veronica Francis in the execution of this
study.
The authors of this article were funded in part by research grants from
the Lily and Ernst Hausmann Trust, the International Centre for Genetic
Engineering and Biotechnology, University of Cape Town, the Medical
Research Council of South Africa, the Discovery Foundation, the National
Research Foundation, and the Wellcome Trust (UK).
References
1. Elliott PM. Classification of cardiomyopathies: Evolution or revolu-
tion? J Am Coll Cardiol 2013; 62: 2073–2074.
2. Lewis BS, Armstrong TG, Mitha AS, Gotsman MS. Hypertrophic
obstructive cardiomyopathy in the South African Bantu. S Afr Med J
1973; 34: 599–604.
3. Maro EE, Janabi M, Kaushik R. Clinical and echocardiographic study
of hypertrophic cardiomyopathy in Tanzania. Trop Doct 2006; 36:
225–227.
4. Lewis BS, Agathangelou NE, Flox H, Toams MA, Barlow JB.
Hypertrophic cardiomyopathy in South African blacks. S Afr Med J
1983; 63: 266–269.
5. Amoah AG, Kallen C. Aetiology of heart failure as seen from a national
cardiac referral centre in Africa. Cardiology 2000; 93: 93.
6. Abegaz B. The impact of echocardiography in the diagnosis of hyper-