CARDIOVASCULAR JOURNAL OF AFRICA • Volume 25, No 4, July/August 2014
AFRICA
169
and January 2012.
8
The control group consisted of 30 female
patients without RA (age 50.7
±
3.4 years).
Patients of the RA group were on methotrexate 15 mg once
per week and prednisolone 5–7.5 mg once daily. The patients had
occasionally been treated with non-steroidal anti-inflammatory
drugs within the previous six months. The disease activity score
(DAS 28), which utilises C-reactive protein (CRP) level, and the
visual analogue score of wellbeing plus the number of tender
and swollen joints, was used in order to evaluate the activity of
RA.
9
We used the Duke activity status index (DASI), a brief
self-administered questionnaire designed to estimate the patient’s
exercise capacity in metabolic equivalents (METs).
10
Out of 38 RA patients, 20 subjects (age 53.4
±
13.5 years)
additionally received infliximab treatment (initially 3 mg/kg;
the same dose two and six weeks after the first infusion, and
thereafter the same dose every eight weeks) for three months.
The remaining 18 patients in the RA group were treated with
prednisolone in increasing doses in accordance with standard
clinical practice.
Patients were examined in the out-patient clinic monthly
to assess clinical status and compliance with therapy. None of
the patients had had ischaemic or arrhythmic events during the
previous year. The RA patients’ biochemical parameters, and
echocardiographic LA and LV function were measured at baseline
and after three months of infliximab and prednisolone therapy.
Electrocardiographic P waves were evaluated. The control subjects
had a single baseline measurement of the examined parameters.
The study protocol was approved by the local ethics committee.
Conventional echocardiography
All echocardiographic examinations were performed by a single
experienced observer blinded to clinical and laboratory data.
Transthoracic echocardiography studies were performed using
a commercially available ultrasound system with a 2.5–3.5 MHz
transducer (ie33, Phillips Medical System, Bothell, Washington,
USA). Patients lay at rest in the left lateral decubitus position,
and apical four-chamber and parasternal views of the LA and
LV were obtained at end-expiratory apnoea. Three cardiac
cycles were stored from each view in ciné-loop format for
subsequent off-line analysis by an investigator blinded to the
patients’ data. Speckle tracking analysis was performed off-line
by commercially available software QLAB 6.0 (Phillips Medical
System, Bothell, Washington, USA).
We measured the following parameters from cross-
sectional echocardiographic images of the cardiac chambers.
(1) End-diastolic interventricular septum thickness (IVS),
end-diastolic posterior wall thickness (PW) of the LV, (2)
end-diastolic volume (EDV), end-systolic volume (ESV) and
ejection fraction of the LV using the modified Simpson’s
method,
11
and (3) maximal (LAVI
max
), pre-contraction (LAVI
preA
)
and minimal (LAVI
min
) LA volumes were measured just before
mitral valve opening, at the beginning of the P wave, and at
mitral valve closure.
All LA volumes were determined using the modified Simpson’s
method. LA volume indices were calculated by dividing the LA
volumes by the body surface area.
12
Pulsed-wave Doppler of transmitral LV inflow was performed
in the apical four-chamber view, with the sample volume placed
at the level of the mitral valve tips, and Doppler variables
were analysed during three consecutive beats. The following
measurements of LV diastolic function were determined: peak
early (E) and late (A) diastolic mitral flow velocity and their ratio
E/A, early diastolic mitral annular velocity (E’), late diastolic
mitral annular velocity (A
′
), deceleration time of the E wave, and
LV isovolumic relaxation time (IVRT).
13
The E/E
′
ratio was used
as an index of LV filling pressures.
Speckle tracking echocardiography
The methods of image acquisition and post-processing of strain
and strain rate measurements with speckle tracking have been
described previously.
14
All images were obtained at a frame rate
of 50 to 80 frames per second.
Briefly, the observer traced the endocardial and epicardial
borders of the LA on an end-systolic frame and the software
automatically tracked the border on the subsequent frames.
Adequate tracking can then be verified in real-time and corrected
by adjusting the region of interest or manually correcting the border
to ensure optimal tracking. The aortic valve closure measured by
Doppler has been identified as end-systole. The software is able to
represent abnormality in time–strain graphs where it is possible to
identify the different phases of the cardiac cycle.
Electrocardiography
After a 20-minute resting period in the supine position, all
subjects underwent a 12-lead ECG recording at a paper speed
of 50 mm/s and 2 mV/cm. The P-wave duration was measured
manually in all simultaneously recorded 12 leads of the surface
ECG by one of the investigators blinded to the study hypothesis.
In each lead the mean values for the three complexes were
calculated. For greater accuracy, the measurements were
performed with callipers and a magnifying lens, as described by
previous investigators.
15,16
The onset of the P wave was defined as the point of first
visible upward departure from baseline for positive waveforms,
and as the point of first downward departure from baseline for
negative waveforms. The return to baseline was considered to be
the end of the P wave. P
max
measured in any of the 12 leads of
the surface ECG was used as the longest atrial conduction time.
The difference between P
max
and minimum P wave (P
min
) was
calculated and defined as P-wave dispersion (Pd
=
P
max
– P
min
).
17
Laboratory assays
CRP was measured using routine methods. IgM rheumatoid
factor (RF) was measured by means of immunonephelometry
using the quantitave NLatex RF system (Dade Behring, Marburg,
Germany) with RF titers of
>
15 IU/ml being considered positive.
Serum levels of total cholesterol, low-density lipoprotein (LDL)
cholesterol, high-density lipoprotein (HDL) cholesterol and
creatinine were determined using an auto-analyser under fasting
conditions on the same day as the other evaluations.
Statistical analysis
Propensity scores, a methodology that can be used to compare
the effectiveness of different treatments and to examine
whether patients included in the two treatment groups were
