Methods
Study Subjects
Local Ethical Committee approval was obtained prior to this prospective
study (2014/07-07). A total of 34 patients (17 of each gender, mean age
9.9±4.9 years) who were being followed at the Dokuz Eylül University
Medical School Allergy Outpatient Clinics were included in the study.
Patients eligible for the study group had a positive sweat test and/or
gene mutation assay and a stable clinical course with no concomitant
cardiac disease. Exclusion criteria included having experienced an acute
lower respiratory tract infection in the last three months, being on a
waiting list for lung transplantation, and poor quality of the
echocardiographic image.
The selected control group consisted of 37 healthy subjects with a
comparable age and sex distribution (18 girls and 19 boys with a mean
age of 9.8±4.3) and normal physical, laboratory, electrocardiography
(ECG) and TTE results.
Echocardiographic studies
Echocardiography examinations were performed with an ultrasound device
(model iE33, Philips Medical Systems, Netherlands) with an S5-1 MHz
transducer by the same observer, who had been blinded to the clinical
condition of the patients. Two researchers who were similarly blinded as
to the clinical condition and grouping of the patients performed the
data analysis off-line.
Two-dimensional echocardiographic images were obtained in standard
parasternal, apical and subcostal views. The following end-diastolic and
end-systolic parameters were measured in M-mode echocardiography in a
parasternal long-axis view: interventricular septal thickness (IVSd and
IVSs, respectively), LV dimensions (LVDd and LVDs), and LV posterior
wall thickness (LVPWd and LVPWs). LV systolic function was assessed from
an apical four-chamber view by measuring the left ventricular ejection
fraction (LVEF) using the modified monoplane Simpson’s rule. Mitral
valve inflow Doppler flow was measured in an apical four-chamber image,
E-wave (early filling), A-wave (late filling) and the E/A ratio were
derived to evaluate LV diastolic function. Pulmonary artery systolic
pressure (PAPs) was determined using the Bernoulli equation on the
Doppler continuous wave measurement of tricuspid valve insufficiency
flow. Right atrial pressure was evaluated using the inferior vena cava
inspiratory collapsibility.
Color TDI images were obtained in the apical view. At least four
consecutive cardiac cycles were recorded for each parameter. A Doppler
frame scanning rate of 100-140 Hz with 40-80 frames/sec was used. Early
diastolic myocardial wave (e’), atrial diastolic myocardial wave (a’),
systolic myocardial wave (s’), total systolic time (TST), ejection time
(ET), isovolumetric relaxation time (IVRT) and isovolumetric contraction
time (IVCT) were measured during the baseline pulse-wave color TDI
examination of the LV free wall and of the interventricular septum. The
myocardial performance index (MPI) was calculated using the following
formula: MPI=IVCT+IVRT/ET. Diastolic function was assessed by
calculating the E/e’ ratio.
For the STE evaluation with simultaneous ECG at frame rates of
70-100 frames/s, apical four-chamber (A4C), apical three-chamber (A3C)
and apical two-chamber (A2C) images were recorded in the apical view and
in the parasternal short axis view the parasternal apical (SAXA),
parasternal medial (SAXM) and parasternal basal (SAXB) images. At least
four consecutive cardiac cycles were recorded for each parameter. The
recorded images were transferred onto DVD and analyzed on a computer
using the QLAP software (Philips Medical Systems). The mitral annulus
lateral and septal and the LV apical endocardial planes were marked for
each three apical chambers, providing for automated generation of the LV
wall by the program. The LV endocardial-myocardial border was adjusted
manually on the systolic frames. Peak systolic strain, peak systolic
strain rate and global strain values were calculated automatically by
the software for six segments (apical, middle, basal) based on septum
and LV lateral wall motion values. In all three parasternal views, the
endocardial-myocardial border was adjusted manually after the program
had automatically generated the ventricular wall. Patients whose results
were abnormal due to poor image quality were excluded from the study.
Statistical Analysis
Statistical analyses were performed using the Statistical Package for
the Social Sciences (SPSS) software, version 22.0 (SPSS Inc.; Chicago,
IL, USA). Continuous data were described as mean ± standard deviation
while categorical data were presented as numbers of patients. The
Chi-squared test was used for comparison of categorical variables, while
parametric continuous variables were compared by Student’s t-test. Data
were checked for normal distribution by the Kolmogorov–Smirnov test. A
value of p<0.05 was considered statistically significant.
Evaluations were repeated by a second, independent observer, to assess
interobserver variability. Interobserver variability was calculated as
the absolute difference divided by the average of the two observations
for all parameters.