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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 1, January/February 2017
AFRICA
63
Univariate associations between echo parameters and outcomes
are presented for the whole analysis population as well as by
key diagnosis groups. Diagnoses were grouped as hypertension,
cardiomyopathy, valvular and other. Valvular was defined as
having rheumatic heart disease or at least one of the following
classified as severe: aortic stenosis or regurgitation, mitral stenosis
or regurgitation. To assess whether an association between an
echo parameter and outcomes differed by diagnosis group, we
tested for the significance of the diagnosis-by-echo parameter
interaction term in the Cox regression model for the outcome.
The number of events in the analysis population limited
development of multivariate models for 180- and 60-day
mortality or re-admission. Because of this, we chose a few echo
parameters in addition to predictors known to be associated with
each outcome in this study population.
Multiple imputations were used with a method that assumes
multivariate normality (SAS PROC MI) to handle missing
values. The imputation model included all covariates under
consideration for the multivariate models. The ranges of imputed
values were restricted to the ranges of the observed values.
Seven imputation datasets were used. Parameter estimates were
averaged across these datasets using Rubin’s algorithm (SAS
PROC MIANALYZE). Backwards selection was used in each
of the seven imputation datasets, with the criterion for staying at
p
<
0.10. Predictors that were significant in the majority of the
imputed datasets were kept in the final model. SAS release 9.2
(SAS Institute, Cary, NC, USA) was used for analyses.
Results
There was a total of 1 006 patients in the THESUS-HF registry,
3
of whom 954 had an echocardiogram performed within four
weeks before to two weeks after enrollment. Among these 954
patients, the mean age
±
SD of the patients was 52.3
±
18.2 years,
469 (49.2%) were men, the predominant race was black African
(99.1%), 11.4% of patients had diabetes mellitus and 9.0% had
hyperlipidaemia. The mean left ventricular ejection fraction
(LVEF)
±
SD was 39.4
±
16.4%, the initial systolic blood pressure
was 130.7
±
33.5 mmHg, and heart rate was 104
±
21.4 beats per
min (Table 1).
Heart failure was most commonly due to hypertension (
n
=
380; 40.9%), followed by rheumatic valvular heart disease (
n
=
133; 14.3%), and idiopathic dilated cardiomyopathy (
n
=
129;
13.9%). Ischaemic heart failure was present in only 71 (7.6%)
patients (Table 1).
The distribution and proportion of missing values for each
echocardiographic parameter are presented in Table 1. LVEF
was available for 897 patients and was missing for 6.0% of
patients. LVEF was
<
50% in 654 (73%) patients and ≥ 50%
in 243 (27%) patients. Patients’ characteristics according to
LVEF are presented in Table 1. Patients with HF with reduced
ejection fraction had higher proportions of males and peripheral
oedema, and lower systolic blood pressure, higher heart rate and
lower estimated glomerular filtration rate, on average.
Univariate associations between the echo predictors and the
outcomesbydiagnosis groups (hypertensiveheart disease, valvular
heart disease and other) suggest that none of the associations of
echo parameters with outcomes differed significantly among the
diagnostic groups (Tables 2, 3). Univariate associations of echo
predictors with 60-day death or re-admission and with 180-day
death are shown in Tables 4 and 5, respectively. Heart rate and
left atrial size were associated with death or re-admission within
60 days. Heart rate, left ventricular posterior wall thickness and
presence of aortic stenosis were associated with the risk of death
up to 180 days.
The multivariate models suggest left ventricular end-systolic
diameter, interventricular septal thickness in diastole, posterior
wall thickness in diastole, left atrial size and E/A wave ratio
did not add significantly to prediction of 60-day death or
re-admission, while left ventricular posterior wall thickness
added to clinical variables in the prediction of 180-day mortality
(Tables 2, 3).
Table 2. Univariate associations between echo predictors and 60-day death or re-admission by diagnosis groups
Echocardiographic parameter
Hypertensive CMP (
n
=
338)
Valvular (
n
=
217)
Other (
n
=
399)
Interaction
p
-value
Hazard ratio
(95% CI)
p
-value
Hazard ratio
(95% CI)
p
-value
Hazard ratio
(95% CI)
p
-value
LVEDD (mm)
0.98 (0.95–1.01)
0.15 1.02 (0.99–1.05)
0.29 1.01 (0.99–1.03)
0.49 0.17
LVESD (mm)
0.98 (0.96– 1.00)
0.087 1.01 (0.98–1.04)
0.47 1.00 (0.98–1.02)
0.92 0.20
IVSTd (mm)
0.98 (0.89–1.09)
0.76 0.98 (0.88– 1.10)
0.77 0.93 (0.85–1.02)
0.12 0.64
PWTd (mm)
1.03 (0.91–1.15)
0.68 0.97 (0.85– 1.10)
0.59 0.93 (0.84–1.04)
0.19 0.47
LV mass
1.00 (1.00–1.00)
0.44 1.00 (1.00–1.00)
0.63 1.00 (1.00–1.00)
0.59 0.62
LVEF (%), per 5% increment
1.07 (0.97–1.18)
0.16 0.99 (0.89– 1.11)
0.86 0.99 (0.91–1.08)
0.82 0.42
Left atrial size (A-P) (mm)
1.02 (0.97– 1.06)
0.46 1.01 (0.98– 1.05)
0.57 1.00 (0.97– 1.03)
0.97 0.83
Left atrial size (planimetry) mm
2
1.00 (1.00–1.00)
0.083 1.00 (1.00–1.00)
0.49 1.00 (1.00–1.00)
0.055 0.73
E/A ratio per doubling
0.93 (0.65–1.31)
0.67 1.67 (0.75– 3.75)
0.21 1.15 (0.85–1.55)
0.37 0.35
E-wave deceleration time (ms)
1.00 (0.99–1.00)
0.65 1.00 (0.99–1.00)
0.24 1.00 (0.99–1.01)
0.73 0.77
MV A-wave duration
1.01 (1.00–1.02)
0.25 1.01 (1.00–1.01)
0.049 0.99 (0.99–1.00)
0.17 0.056
MV E/A ratio grades
Grade 1: impaired relaxation
(reference group)
0.32
(reference group)
(reference group)
0.63 0.18
Grade 2: pseudonormal
1.63 (0.66–3.98)
–
0.78 (0.29–2.09)
Grade 3: restrictive filling
0.93 (0.39–2.18)
–
1.13 (0.49–2.58)
LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; IVSTd, interventricular septal thickness in diastole;
PWTd, posterior wall thickness in diastole; LV, left ventricular; LVEF, left ventricular ejection fraction; A-P, antero-posterior; MV, mitral valve.
Heart rates are for an increment of one unit in the predictor unless otherwise noted. Valvular group defined as rheumatic heart disease or having
severe mitral stenosis/regurgitation, aortic stenosis/regurgitation.