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

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 3, May/June 2016

154

AFRICA

univariate and multivariate regression analysis, with a focus

on mortality rather than time to death, therefore justifying the

use of Cox’s proportional hazards model rather than logistic

regression analysis.

Results

The study cohort comprised 43 patients with HCM. The clinical

characteristics and co-morbid status of the study population

at the initial evaluation are shown in Table 2. The mean age of

HCM patients studied was 38.5

14.3 years; 25 (58.1%) were

male. Thirteen (30.2%) were black Africans, and the majority

(62.8%) were of mixed ancestry. Twenty-six (60.5%) had first-

degree relatives with HCM and five (11.6%) had a family

history of sudden cardiac death (SCD) in a first-degree relative.

Symptoms of palpitations (79.1%), angina (65.1%), fatigue

(58.1%) and effort-related breathlessness (55.8%) were frequently

reported by the patients. Ten (23.3%) had a New York Heart

Association (NYHA) functional capacity of class III at the

initial assessment. An ejection systolic murmur was reported in

18 (41.9%) of patients.

The

electrocardiographic

and

echocardiographic

characteristics of the study population are shown in Table

2. Four (9.3%) of the HCM patients had atrial fibrillation at

diagnosis. On echocardiography, the mean left ventricular (LV)

septal thickness in diastole, LV ejection fraction (LVEF) and left

atrial diameter were 1.9

0.7 cm, 71.5

8.3% and 3.5

0.8 cm,

respectively. Left ventricular outflow tract (LVOT) obstruction,

with a resting gradient of greater than 10 mmHg was found in 12

(27.9%) patients. Evidence of diastolic dysfunction was present

in the majority of patients, and the mean E/A ratio was 1.2

0.4.

Spectrum of mutations that cause HCM in South

Africans

Of the 43 patients diagnosed with HCM, 42 were screened for

the common founder mutations previously described in the

South African population, and all 42 were found to be negative

for these variants.

Further molecular genotypic analysis was

undertaken in 35 of these HCM patients for 15 cardiomyopathy-

associated genes. Of these 35 probands, mutation screening

yielded disease-causing mutations in 10 unrelated individuals

(28.6%) (Table 3). The disease-causing mutations were found in

two out of the 15 genes screened, with the majority in

MYH7

(

6 probands; 60%) and the rest in

MYBPC3

(

4 probands;

40%). Two of the

MYH7

mutations were novel, and disease-

causing mutations were found in all ethnic groups tested. No

single disease-causing mutation occurred in more than one study

subject.

There were three genetic variants of unknown significance

found in

MYBPC3,

which were not observed in 195 population

controls: c.1224-19G

A, c.1790

A, and c.133G

A. In addi-

tion, a large number of known polymorphisms were found in

16 probands in

MYBPC3

(tmp_esp_11_47355301, rs113941605

andrs113658284),

MYH7

(rs149439730,rs45523835,rs145738465,

rs202205780, rs61737803, rs146858930, rs36211714, rs45501694,

and rs111626355),

TNNT2

(rs113471285, and rs115805892),

TPM1

(tmp_esp_15_63356347),

MYL

3 (rs199474709),

CSRP3

(rs112848043),

FHL1

(rs182106777),

PRKAG2

(rs116605521,

and rs113234987),

GLA

(rs151195362), and

LMNA

(rs12117552,

Table 2. Demographic, clinical, electrocardiographic and

echocardiographic features at presentation in patients with hypertrophic

cardiomyopathy compared to three large contemporary international

reports from North America,Taiwan and Saudi Arabia

Medical history

South

Africa

(

43)

North

America

(

277)

Taiwan

(

163)

Saudi

Arabia

(

69)

Age at diagnosis (years)

38.5

14.3 47

22 60.9

12.1 42

Males

25 (58)

152 (55) 84 (52)

43 (71)

Ethnicity (%)

Black/African

13 (30)

White/Caucasian

2 (5)

277 (100)

Coloured/mixed ancestry

27 (63)

Indian ancestry

1 (2)

Taiwanese

163 (100)

Arab

69 (100)

First-degree relative with HCM 26 (61)

21 (8)

–

2 (5)

Second-degree relative with HCM 7 (16)

–

Has family history of SCD

5 (12)

–

4 (9)

NYHA functional class

I and II

33 (77)

–

III and IV

10 (23)

Symptoms

174 (63)

Fatigue

25 (58)

–

Dyspnoea

24 (56)

121 (74)

31 (65)

Palpitations

34 (79)

28 (17)

5 (7)

Angina

28 (65)

111 (68)

–

Presyncope/syncope

12 (28)

20 (12)

2 (4)

Smoking

19 (31)

–

Hypertension

12 (28)

–

28 (17)

–

Diabetes

0 (0)

–

29 (18)

–

Alcohol consumption

9 (21)

–

Dyslipidaemia

6 (14)

–

Coronary artery disease

3 (7)

–

29 (18)

–

COPD

2 (5)

–

HIV infection

2 (5)

–

Medical examination

Heart rate

71.3

12.7 –

–

sys

125.8

19.2 –

–

dia

75.8

11.3 –

–

Pedal oedema

5 (11.6)

–

Ejection systolic murmur

18 (41.9)

–

Electrocardiographic findings

Sinus rhythm

39 (90.7)

–

Atrial fibrillation

4 (9.3)

–

34 (21)

–

QRS abnormalities present

12 (28)

–

Voltage criteria for LVH

22 (51)

–

137 (84)

60 (87)

Presence of pathological Q waves 12 (28)

–

T-wave inversion

34 (79)

–

108 (66)

–

Left atrial hypertrophy

10 (23)

–

LBBB

4 (9)

–

RBBB

2 (5)

–

PR prolongation

2 (5)

–

Echocardiographic findings

LVEDD (cm)

4.1

0.8

–

4.5

0.5

–

LVESD (cm)

2.7

0.6

–

2.4

0.4

–

IVS

dia

(cm)

1.9

0.7 2.2* 1.9

0.4 –2.1

0.7

IVS

sys

(cm)

2.1

0.7

–

LVPFW

dia

(cm)

1.2

0.4

–

1.1

0.3 1.3

0.4

LVEF (%)

71.5

8.3

–

Left atrial size (cm)

3.5

0.8

–

3.8

0.7

–

SAM

9 (21)

–

80 (49)

39 (57)

LVOT obstruction

12 (28)

–

78 (48)

28 (41)

E/A ratio

1.2

0.4

–

1.5 (0.9–2.1)

Pattern of hypertrophy

Sigmoid

13 (30)

75 (27)

–

8 (12)

Catenoid

23 (53)

92 (33)

29 (42)

Neutral

6 (14)

65 (23)

25 (36)

Apical

1 (2)

5 (2)

7 (10)

All results are means

standard deviation, unless otherwise indicated.

*No standard deviation given.

dia

, diastolic blood pressure; BP

sys

, systolic blood pressure; COPD, chronic obstruc-

tive pulmonary disease; E/A, ratio of early (E) to late (A) ventricular filling velocities

on Doppler echocardiography; IVS

dia

, interventricular septal thickness in diastole;

IVS

sys

, interventricular septal thickness in systole; HCM, hypertrophic cardiomyopa-

thy; HIV, human immunodeficiency virus; LBBB, left bundle brunch block morphol-

ogy on electrocardiography; LVEDD, left ventricular end-diastolic dimension; LVEF,

left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension;

LVH, left ventricular hypertrophy; LVPFW

dia

, left ventricular posterior free-wall

thickness in diastole; LVOT, left ventricular outflow tract; NYHA, New York Heart

Association functional classification for severity of breathlessness; RBBB, right

bundle brunch block morphology on electrocardiography; SAM, systolic anterior

motion of the anterior mitral valve leaflet; SCD, sudden cardiac death.