CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 4, May 2012
192
AFRICA
without normal distribution. Pearson correlation was used for
the correlation analysis. The mean inter-observer difference
and inter-class coefficients were used to evaluate inter-observer
variability. A two-tailed
p
-value
<
0.05 was considered
statistically significant.
Results
Baseline characteristics of patients including demographic,
clinical and laboratory parameters are outlined in Table 1. The
study population was mostly elderly patients and 69.4% were
over 65 years. Approximately two-thirds of the patients were
white males. All patients were on a drug affecting the renin–
angiotensin–aldosteron system. NYHA functional class II was
the most common category in the population. No discontinuation
of the study drug was observed during the study period.
At the end of the study, vital parameters of patients including
systolic (110
±
15 vs 100
±
15 mmHg,
p
<
0.001) and diastolic
(72
±
10 vs 68
±
10 mmHg,
p
<
0.001) blood pressure and heart
rates (84
±
11 vs 74
±
11 bpm,
p
<
0.001) were significantly
decreased, as expected. However, there were no significant
changes in the left ventricular ejection fraction and NYHA
functional class of the patients between the baseline and follow-
up values at one and three months (32.3
±
5.0 vs 32.4
±
4.9%,
p
=
0.327 and 2.3
±
0.6 vs 2.2
±
0.5%,
p
=
0.103), respectively.
QTc and QTcd were measured at baseline and in the first and
third month of the study. The measurements and calculations
were performed by two independent observers blinded to the
study protocol. The mean values of the QT dynamics from
two independent observers are given in Table 2. In the whole
population, both QTc and QTcd were significantly decreased
in the first and third months compared to baseline values (Table
2). QTc and QTcd values correlated significantly between the
two observers. Inter-class coefficients and mean inter-observer
differences at baseline and in the first and third months are
presented in Table 3.
In male subjects, both QTc and QTcd were significantly
decreased in the first and third months compared to baseline
values. In female subjects, both QTc and QTcd were significantly
decreased in the third month compared to baseline values.
However, in the first month of follow up, no significant decrease
was detected in QTc or QTcd compared to baseline values. In
addition, both QTc and QTcd were significantly decreased in
the third month compared to the first month (data not presented).
There was a significant positive correlation between age and
baseline QTcd in the whole study population (
β
=
0.567,
p
<
0.001). There was no significant difference between patients
in NHYA class I–II and III–IV, according to QTc and QTcd at
baseline and in the first and third months (
p
>
0.05 for all).
Discussion
We found that nebivolol therapy significantly improved both
QTc and QTcd parameters in patients with systolic heart failure,
which has not been reported in the literature before. Sympathetic
tone, excitation–contraction coupling and myocardial fibrosis
may be the reasons for impaired QT dynamics in heart failure.
Both QTc and QTcd are the indicators of the heterogeneity of
myocardial repolarisation and electrical instability.
8,11
The action
potential is prolonged and repolarisation is delayed in heart
failure patients.
The QT interval on the surface ECG is a readily measurable
reflection of cardiac repolarisation. The QT interval is an
index of ventricular repolarisation that is directly influenced
by myocardial health and autonomic nervous system activity.
Patients with heart failure and prolonged action potential
durations have abnormalities of the QT interval. In a small group
TABLE 1. BASELINE DEMOGRAPHIC, CLINICAL
AND LABORATORY CHARACTERISTICS OF
THE STUDY POPULATION
Characteristic
Value (
n
=
72)
Age (years)
71.0
±
10.4
Male (%)
45 (62.5)
Diabetes mellitus (%)
6 (8.3)
Smoking (%)
13 (18.1)
Hypertension (%)
23 (31.9)
CCB use (%)
5 (6.9)
ACE inhibitor use (%)
62 (86.1)
ARB use (%)
10 (13.9)
Statin use (%)
10 (13.9)
Aldosterone antagonist use (%)
21 (29.2)
Diuretic use (%)
68 (94.4)
Digoxin use (%)
16 (22.2)
NYHA class
I (%)
4 (5.6)
II (%)
47 (65.3)
III (%)
19 (26.4)
IV (%)
2 (2.8)
LVEF (%)
32.3
±
5.0
Creatinine (mg/dl)
0.96
±
0.27
Na (mmol/l)
136.3
±
4.2
K (mmol/l)
4.2
±
0.6
Ca (mmol/l)
2.37
±
0.12
ACE: angiotensin converting enzyme; ARB: angiotensin receptor blocker;
CCB: calcium channel blocker; LVEF: left ventricular ejection fraction;
NYHA: NewYork Heart Association.
TABLE 2. QT DYNAMICS IN THEWHOLE POPULATION
Characteristic
Baseline
First month
Third month
QTc (ms)
455.3
±
26.7 441.2
±
25.7* 436.0
±
28.7*
QTcd (ms)
65.6
±
5.3
58.2
±
5.6** 56.0
±
6.2*
The mean values of two independent observers are presented.
*
p
<
0.001 for baseline to first month and baseline to third month.
**
p
=
0.001 for baseline to first month.
TABLE 3. INTER-OBSERVER DIFFERENCESAND
INTER-CLASS COEFFICIENTS BETWEEN TWO
OBSERVERS FOR QT DYNAMICS
Characteristics
Mean
inter-
observer
difference
(ms)
Range (ms)
Inter-
class
coeffi-
cient
95% CI
p
-value
QTc baseline
–2.8 –15 to
+
20 0.986 0.978–0.991
<
0.001
QTcd baseline
–0.5 –2.5 to
+
3.5 0.999 0.999–1.000
<
0.001
QTc month 1
–3.0 –20 to
+
20 0.995 0.993–0.997
<
0.001
QTcd month 1 –0.5 –2.5 to
+
3.5 0.999 0.999–1.000
<
0.001
QTc month 3
–2.6 –15 to
+
20 0.993 0.988–0.995
<
0.001
QTcd month 3 –0.5 –3.0 to
+
3.5 0.999 0.999–1.000
<
0.001
