CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 4, May 2012
AFRICA
201
The study enrolled patients prospectively from February
to September 2007. Patients with severe, chronic isolated MR
underwent comprehensive quantitativeDoppler echocardiography
performed by one trained echocardiographer (RP). Patients were
excluded if they had acute MR, MR due to ischaemic heart
disease or cardiomyopathy, previous valve surgery and associated
aortic or congenital valve disease. Patients with associated mitral
stenosis were excluded if the valve area was less than 2.0 cm
2
.
Clinical evaluation and management of the patients were
conducted by their independent clinicians. Assessment of
symptoms was determined clinically by the New York Heart
Association (NYHA) classification, and atrial fibrillation was
evaluated by electrocardiography. Doppler echocardiographic
recordings and blood samples were collected simultaneously
and estimation of the NT-proBNP levels were processed
independently.
Control subjects with severe MR were selected from the
cardiology outpatient follow-up clinic where they were assessed
as not requiring surgery in the short term and were receiving
medical therapy. Controls were selected as severe MR, but
without evidence of ischaemic heart disease, as it is known that
NT-proBNP is activated in the presence of ischaemia.
3
Colour Doppler echocardiography was performed on all
patients using a Siemens Sequoia machine (Acuson, Germany).
Dimensions and wall thickness were measured according to the
American Society of Echocardiography guidelines using the
leading-edge method,
4
and EF was measured from the apical
four-chamber view using the modified Simpson’s method. The
rate of rise of pressure (dP/dT) was also calculated as a measure
of ventricular systolic function. The six frequently applied
echocardiographic variables described by Thomas
et al
.
5
were
used to evaluate MR. Mitral regurgitation was quantified by
measurement of the regurgitant volume and fraction.
TDI was performed in the apical four-chamber view. The
myocardial systolic wave (Sm) velocity, the diastolic indices,
namely early myocardial (Em) and atrial contraction (Am)
peak velocities, Em/Am ratio, and early diastolic filling ratios
(transmitral/annular) (Em/Ea ratio) were measured. The ratio
of the E wave across the mitral valve to the annulus E wave
on tissue Doppler (E/Ea) was used as an estimate of the LV
filling pressure. All echocardiographic measurements were
performed by a single echocardiographer (RP) blinded to all other
measurements. The images and measurements were reviewed
off-line by a trained cardiologist (DPN). The intra-observer
variability for the measurements of proximal isovelocity surface
area (PISA) and TDI was
<
5%.
For measurement of NT-proBNP, venous blood samples were
taken in gel-filled tubes with the patient resting quietly at the
time of echocardiography. Additional samples were taken from
subjects undergoing mitral valve replacement at one and six
weeks post surgery.
Statistical analysis
SPSS for Windows version 15.0 was used for the statistical
analysis. Clinical variables were normally distributed and
expressed as mean
±
SD. NT-proBNP levels were log-transformed
for statistical analysis. Group comparisons were performed with
ANOVA,
t
-test or chi-square tests. Associations of baseline
NT-proBNPwere testedwith linear and non-parametric regression
(categorical variables). The time course of NT-proBNP within
the cases was evaluated using paired
t
-tests. The discriminating
capacity of the NT-proBNP for separating surgical cases from
controls was assessed by the construction of ROC curves.
Bivariate analysis was performed to assess the ability of the
different parameters in predicting a favourable outcome using an
NT-proBNP level of 50 pmol/l.
Results
A total of 54 patients with severe rheumatic mitral regurgitation
were enrolled in the study and surgical cases were followed up
for six weeks. Their baseline characteristics are shown in Table
1. All but one of the patients in our sample population were
of African descent (98%). There were 27 control patients with
severe chronic rheumatic mitral regurgitation who were recruited
from the cardiology follow-up clinic.
Only one patient in the control group had markedly elevated
systolic pressure (63 mmHg) together with NYHA class III
symptoms. This patient subsequently had a valve replacement
seven months after the echocardiographic and NT-proBNP
assessment.
The orifice area was markedly increased in 12 patients in the
study group (Table 2). Group comparisons revealed that early
diastolic filling ratios (E-mitral/E-annulus) was higher in the
study group (
p
=
0.04). A similar pattern was observed with
NT-proBNP level, which was elevated in both groups, but was
markedly higher (
p
<
0.001) in the study group (Table 3).
The immediate post-operative period showed a rise in
NT-proBNP levels from pre-operative levels (262
±
224 pmol/l)
to a mean of 395 pmol/l at one week, and subsiding thereafter to
94 pmol/l at six weeks (see Fig. 1). These changes were mirrored
by a significant reduction in the left atrium (LA) size and
volume, as well as in the LV chamber dimension to levels similar
to the control population group (Table 4). It is noteworthy that
inasmuch as there was a slight reduction in the end-diastolic
volume (EDV) and end-systolic volume (ESV), these changes
were not statistically significant. Although the TDI systolic wave
indices were unchanged between the two time points, there was
a significant increase noted in the early diastolic filling ratios,
suggesting a further rise in the left ventricular filling pressures
at six weeks.
Four patients exhibited persistently elevated NT-proBNP
levels at six weeks compared to the other study cases. The ejection
fraction fell in three of these patients post-operatively, and was
accompanied by little change in the end-systolic dimension
(ESD) and NT-proBNP values compared to pre-operative levels.
TABLE 1. BASELINE (PRE-OPERATIVE)
CHARACTERISTICS IN SEVERE MR
Variables
Controls (
n
=
27)
Study (
n
=
27)
p
-value
Age
23
±
13
20
±
11
0.08
Males/females
7/20
7/20
1.000
NYHA I–II
24
10
0.001
NYHA III–IV
3
17
Heart failure
1
5
EF (mean
±
SD)
67
±
6
67
±
9
1.000
Diuretics
24
20
0.307
ACE inhibitors
25
25
1.000
Atrial fibrillation
6
10
0.372
NYHA
=
NewYork Heart Association class; EF
=
ejection fraction.
