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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 5, September/October 2018
306
AFRICA
Methods
Between February 2008 and November 2011, 57 consecutive
patients (mean age 54.1
±
16.3 years, male 68.4%) with typical
symptoms and signs of ADHF and with low left ventricular
ejection fraction (LVEF
<
40%) were enrolled in this study.
12
During the hospital stay, all of the patients received appropriate
HF treatment measures in accordance with contemporary
guideline recommendations.
13
Patients with concomitant unstable ischaemic diseases,
those presenting with shock, severe renal failure [GFR
estimated by Modification of Diet in Renal Disease (MDRD)
equation
<
30 ml/min/1.73 m
2
] or hepatobiliary dysfunction,
anaemia or haematological disease, acute or chronic infection
and inflammation, malignant neoplasms and patients with
echocardiographic LVEF values
≥
40% were excluded. A gender-
and age-matched control group (
n
=
31) with normal LVEF and
renal function was included to compare plasma NT-proBNP and
cystatin C levels with the patient group.
Surviving participants were clinically followed up every
three months for three years by means of visits or telephone
interviews. In the case of death during the follow-up period,
follow-up duration was calculated in months (time interval from
admission to death) for that subject. Mean follow-up duration
for the entire group was 17.2 months.
The primary clinical endpoint of this study was determined as
all-cause mortality. From each patient, oral informed permission
for the study was obtained by one of the investigators, and the
study protocol was approved by the local ethics committee of
our hospital.
Blood samples for biochemical parameters, including
haemoglobin, blood urea nitrogen (BUN), creatinine, electrolytes,
cystatin C and NT-proBNP were drawn at admission for
ADHF. GFR was determined using two different contemporary
formulae: the MDRD and the Cockroft–Gault formulae.
14,15
For
cystatin C assessment, an immediate centrifugate of the collected
sample was obtained. Aliquot serum samples were stored in
microcentrifuge tubes at −80°C until assayed.
Measurements of cystatin C levels were performed using
a particle-enhanced immune nephelometric method (Dade
Behring GmbH, Liederbach, Germany). Intra-assay and inter-
assay coefficients were 2.5 and 2.0%, respectively. NT-proBNP
was measured by ARCHITECT i2000 platform (Abbott
Laboratories, Abbott Park, Illinois).
All patients underwent standard echocardiographic imaging
in the left lateral decubitus position with a commercially
available device (Vivid 7 Ultrasound System; GE, Horten,
Norway) on admission. The echocardiographic assessments
were based on the criteria proposed by the American Society of
Echocardiography. A modified Simpson’s method was used for
LVEF calculation.
16
Statistical analysis
Statistical analyses were performed using SPSS for Windows,
version IBM 11.5 (SPSS Inc, Chicago, IL, USA). Continuous
variables are presented as the mean
±
standard deviation (SD) or
median (min–max), where applicable. Categorical variables are
presented as percentages. The Student’s
t
-test was used to analyse
mean differences between two independent groups. The Mann–
Whitney
U
-test was employed for identification of medians
between two independent groups. As both plasma cystatin C
and NT-proBNP levels were normally distributed. Correlation
coefficients and their significance were calculated with Pearson’s
correlation test.
To define the predictors that changed in-hospital mortality,
multiple logistic regression analyses were used. Odds ratios (OR)
and 95% confidence intervals (CI) for the different independent
variables were also determined. Univariate and multivariate Cox
regression analyses were performed to delineate independent
predictors of mortality during 36 months of follow up. A
p
-value
<
0.05 was considered statistically significant.
Results
In this study, 57 subjects whomet the inclusion criteria constituted
the final research group. Plasma NT-proBNP and cystatin C
levels were determined among patients with ADHF and the
control subjects (
n
=
31). Plasma NT-proBNP concentrations of
the patients were greater than in the control group (641.6
±
31.7
vs 23.2
±
31.7 pg/ml,
p
<
0.001). However, there were no notable
differences in plasma cystatin C levels between the patient and
control groups (1.27
±
0.48 mg/l in the patients vs 1.11
±
0.43
mg/l in the controls,
p
=
0.095).
Baseline demographic characteristics of the patients are
reviewed in Table 1. During the in-hospital period, seven (12.3%)
patients died. Comparisons of variables were made between
survivors and those who died during the hospital stay.
There were no notable differences regarding gender,
hypertension, diabetesmellitus, smoking andmyocardial infarction
between the groups (
p
> 0.05). However, the subjects who died
during the in-hospital period were younger than the survivors
(47.4
±
17.5 vs 60.8
±
15.8 years,
p
=
0.043). Also, the rate of prior
cerebrovascular accident was significantly higher in patients who
died (28.6 vs 6.0%,
p
=
0.048). Moreover, among patients who died
during the hospital stay, lower sodium concentrations, and higher
cystatin C and NT-proBNP levels were observed (
p
=
0.003,
p
=
0.023,
p
=
0.001, respectively) (Table 2).
Baseline echocardiographic characteristics of the patients are
reviewed in Table 3. There were no differences between the two
groups regarding echocardiographic parameters (
p
> 0.05).
Table 1. Baseline demographic characteristics of the study population
Variables
In-hospital survivors
(
n
=
50)
In-hospital deaths
(
n
=
7)
p
-value
Age (years)
60.8
±
15.8
47.4
±
17.5 0.043
Male gender,
n
(%)
34 (68.0)
5 (71.4)
0.855
Diabetes mellitus,
n
(%)
15 (30.0)
4 (57.1)
0.154
Hypertension,
n
(%)
24 (48.0)
5 (71.4)
0.246
Hyperlipidaemia,
n
(%)
12 (24.0)
1 (14.3)
0.566
Cigarette smoking,
n
(%)
6 (12.0)
1 (14.3)
0.863
History of MI,
n
(%)
9 (18.0)
2 (28.6)
0.507
History of CVA,
n
(%)
3 (6.0)
2 (28.6)
0.048
History of PCI,
n
(%)
5 (10)
1 (14.3)
0.729
History of CABG,
n
(%)
6 (12.0)
1 (14.3)
0.863
New diagnosis of HF,
n
(%)
7 (14)
0 (0.0)
0.291
BMI (kg/m²)
26.1
±
4.9
22.4
±
3.8 0.062
Hospitalisation length (days)
15.2
±
22.2
23.6
±
27.2 0.345
NYHA functional class
3.2
±
4.9
3.4
±
5.6 0.237
BMI: body mass index, CABG: coronary artery bypass grafting, CVA: cerebro-
vascular accident, HF: heart failure, MI: myocardial infarction, NYHA
:
New
York Heart Association, PCI: percutaneous coronary intervention.