CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 10, November 2012
542
AFRICA
been shown to be an independent cause of a LQTc.
24
No clear
link is evident in the literature between hypercholesterolaemia
and QTc interval.
The purpose of our study was to evaluate LQTc as an
independent prognostic indicator with regard to mortality and
systolic and diastolic dysfunction in the context of IHD.
Furthermore, we endeavoured to assess, in a state hospital setting
in the Western Cape, whether LQTc correlated with triple-
vessel coronary artery disease (TVCAD), or was significantly
associated with hypercholesterolaemia, diabetes mellitus,
smoking, hypertension or a family history of IHD.
Methods
The study was approved by the Committee for Human Research,
Faculty of Health Sciences, Stellenbosch University. All patients
signed informed consent before coronary angiography. All data
were collected and recorded as part of routine clinical care.
This was a single-centre, prospective study, enrolling a cohort
of patients who were eligible for coronary angiography from
2006
to 2009 at Tygerberg Academic Hospital. Due to the time
limit imposed by the authors collecting data, rotating through
the coronary care unit, not all eligible patients could be enrolled.
Patients with atrial fibrillation, bundle branch blocks, no ECG
in the 24 hours before angiography, or renal failure (creatinine
≥
200
μ
mol/l) were excluded from the study.
25,26
QTc intervals were recorded on the last ECG taken during
the 24 hours before coronary angiography, and designated long
QTc (LQTc) or normal QTc (NQTc). The primary outcome was
six-month survival. Secondary outcomes included correlation of
QTc intervals with left ventricular ejection fraction (LVEF), left
ventricular end-diastolic pressure (LVEDP), TVCAD, diabetes
mellitus, smoking, systemic hypertension, a family history of
IHD and dyslipidaemia.
Measurement of QT interval
As the accuracy of automated measurements of the QT interval
is questionable, partly because of inconsistency between
manufacturers in terms of the digital algorithms employed in
various instruments, the QT intervals were measured manually.
5
These values were then compared with the algorithm-based ones.
The QT interval was measured from the start of the QRS
complex to the end of the T wave, using a Digimatic
®
digital
caliper (0.01-mm scale) with an autostopper (Mitutoyo
Corporation, Mita, Japan). When a T wave was biphasic, or
nearly so, the QT interval was measured to include the final
return to baseline. No U waves were encountered, and therefore
no decision as to the endpoint of measurement in such instances
had to be taken. The digitally calculated heart rate was obtained
from the ECG, and the QTc was computed by means of Bazett’s
formula.
4,5
Definition of parameters and endpoints
The QTc was considered prolonged if
>
440
ms in males and
>
460
ms in females. The follow-up period started on the day
of coronary angiography (day 0), and ended after six months
(
day 180) had elapsed. Survival was determined telephonically
at the end of six months. The LVEF (as an index of systolic
function) was determined either by ventriculography at the time
of coronary angiography or, in the case of ventriculography not
having been performed, by transthoracic or trans-oesophageal
echocardiography. The LVEDP (as an index of diastolic function)
was measured at the time of coronary angiography via a fluid-
filled endocardiac catheter.
TVCAD was defined as a
>
70%
stenosis of all three of
the following vessels: the right main coronary artery, the left
circumflex artery and the left anterior descending coronary
artery or the right main coronary artery, in conjunction with the
left main stem, as assessed at the time of coronary angiography.
The interventional cardiologist decided how to treat stenosed
coronaries, i.e. medically, percutaneously or surgically, and the
investigators were blinded to subsequent treatment.
Diabetes mellitus was defined as symptoms of diabetes plus a
random blood glucose concentration of
≥
11.1
mmol/l, or fasting
plasma glucose of
≥
7.0
mmol/l. This accords with the American
Diabetes Association clinical practice recommendations of
2006.
27
In addition, patients were considered diabetic if they
were taking anti-diabetic medication.
Smoking was defined as the use of any tobacco on a daily
basis at any stage of the patient’s life. Systemic hypertension was
defined as a blood pressure recording of
≥
140/90
mmHg as per
National Cholesterol Education Program Adult Treatment Panel
III Guidelines of 2004.
28
A family history of IHD was considered
positive if it was present in a male first-degree relative of
≤
55
years, or in a female first-degree relative of
≤
65
years.
28
Hypercholesterolaemia was defined as a total, non-fasting
serum cholesterol level
>
5
mmol/l. The non-fasting nature was
accepted as a result of the short period of hospitalisation of most
patients undergoing angiography.
Statistical analysis
Data were analysed by the Stellenbosch University Centre for
Statistical Consultation (CSC) using STATISTICA version
9 (
StatSoft
®
Inc, Tulsa, OK, USA, 2009). The Kaplan–Meier
method was used to create survival curves for NQTc and LQTc
groups and a log-rank test was used to compare the two curves
and generate a
p
-
value. NQTc and LQTc groups were compared
with regard to LVEF, LVEDP and serum cholesterol with a
Mann–Whitney
U
test. Categorical data (diabetes mellitus,
smoking, hypertension and family history of IHD) were tested
for an association with LQTc using a chi-square test. Statistical
significance was defined as
p
<
0.05.
Results
Of the 2 023 patients who were catheterised, 321 were enrolled
(80.2%
Coloured, 18.8% white, 1.0% black) (mean age 56
±
12
years; range 24–84) (Fig. 1). One hundred and sixteen patients
(36%)
were female (mean age 57
±
10
years; range 29–78) and
205 (64%)
were male (mean age 55
±
12
years; range 24–85) (
p
=
0.168).
Ninety patients (28%) had LQTc.
At six months, 15 (4.7%) of the total population had died,
73%
of whom had a LQTc. Eleven patients (12%) died in the
LQTc group and four (1.7%) in the NQTc group (
p
<
0.01) (
Fig.
2).
The hazard ratio was 10.16 (95% CI: 2.91–35.44).
LQTc patients had normal LVEF but lower than that of the
NQTc cohort (LQTc: 52.9
±
15.4%
vs NQTc: 61.6
±
13.6%;
p
<
0.01) (
Fig. 3) and higher LVEDP at LVEF
>
45% (
LQTc: 19.2
±
9.0
mmHg vs NQTc: 15.9
±
7.5
mmHg;
p
<
0.05) (
Fig. 4). The
