The impact of SCA on LV dimensions and function in both children and adults has been better studied in the developed world than countries like Nigeria where persons with SCA abound. Our study documents cardiac size and LV systolic function of Nigerian children with homozygous
SCA and in addition, correlated these with the age, BSA and haematocrit levels. We found that Nigerian children with SCA have deviations in cardiac dimensions from normal children with enlargements noticed on ECHO ranging from 1.1 to 1.2 times in the Ao and LAD. Similar dilatations of the LA and Ao had been earlier documented in children [9
] as well as adults with SCA [26
Also, we observed increases in the entire LV dimensions of about 1.1 to 1.4 times those of normal children. These were all significantly higher in children with SCA, excepting the LV-posterior wall diameter in diastole just as previously documented [5
]. However, some other authors have documented increase in this parameter in children with SCA [12
]. Lester et al. [4
] observed increased wall thickness in only 20 percent of the older children with SCA. Clinicopathologic studies by Gerry et al. [29
] have shown greater hypertrophy of the left and right ventricles in adults than in children. This appears reasonable considering the progressive increase in LV wall stress in such patients over many years. The younger age population of the present study may be responsible for the lack of significant increase noted in the LV free wall thickness. Even the interventricular
septal diameter in diastole (IVS-Dd) of SCA subjects was significantly larger than that of controls (p=0.007). This is contrary to findings of Lamers et al. [10
] who did not find any difference in septal thickness in the paediatric sickle cell patients even though size and age of the population he studied were similar to ours. However, Cipollotti et al. [6
] reported findings similar to ours in a study of 38 Brazilian children and adolescents.
We also observed that left ventricular hypertrophy (LVH) is a prominent ECHO feature of children with SCA as seen in almost half (44.0 percent). The left ventricular mass (LV-M), which is an estimate of the weight of the LV, was found to be significantly increased in the subjects in our study. The LV-M is derived from the LV-EDD, IVS-Dd and LV-PWDd, and because these parameters were increased in the SCA group, it was only inevitable that the LVM of these patients would be increased. LV-M is thought to increase in SCA when the chamber dilatation alone cannot compensate for the increasing demands placed on the myocardium [26
]. Heart size is closely associated with body size [27
]. Left ventricular mass index (LV-MI) is calculated to standardize measurements of LVM [15
]. Several methods for indexing left ventricular mass have been reported, but it is recommended that height raised to the power of 2.7 (m2.7
) be used as described by deSimone et al. [22
]. This method accounts for close to the equivalent of the effect of lean body mass and excludes the effect of obesity and blood pressure elevation on LV-M [15
]. For children and adolescents, a conservative cut point that determines the presence of LVH is 51 g/m2.7
. All but one of our SCA subjects with LVH had normal relative wall thickness values of less than 0.41 [23
], showing eccentric LVH. Eccentric hypertrophy
is associated with intermediate risk for cardiovascular outcomes while the concentric pattern is associated with higher risk [15
]. Johnson et al. [30
] had earlier reported similar findings. The LV-M increases in SCA when chamber dilatation alone can no longer compensate for the increasing demands placed on the myocardium [26
]. Apart from the volume overload which occurs in SCA, sickling of the blood cells occurring in the microvasculature may create additional strain on the heart thus probably inducing ventricular hypertrophy [26
Thus, it appears agreed upon in the literature that SCA leads to a chamber enlargement of the LA and LV. Since, ascertainment of the LV-MI is very helpful in clinical decision-making; the presence of LVH can be an indication for initiating or intensifying pharmacologic therapy [15
Cardiac enlargement has been long recognized as part of the clinical manifestation of SCA [31
]. Several other authors have documented similar findings in children with SCA [4
]. In SCA, there is a double burden imposed on the cardiovascular system, namely the haemodynamic effect of the anaemia and the influence of the myocardial insult caused by the sickling process [32
]. To compensate for the chronically reduced oxygen carrying capacity, cardiac output is increased in persons with SCA [32
]. Cardiac output is dependent on heart rate and stroke volume [6
]. In chronic anaemia, the heart rate is increased due to hypoxia-stimulated
chemoreceptors and increased sympathetic activity [34
]. However, the successful adaptation to chronic SCA results in only minimal increases in heart rate [28
]. Thus, the major contributor to the increased cardiac output in these children is an increase in stroke volume [25
]. The preload increases owing to the volume overload and afterload is reduced because of decreased peripheral resistance [6
]. Thus, it is not surprising to find significant dilatation of the cardiac chambers we report.
In the present study, cardiac function was assessed using the fractional shortening (FS) and the ejection fraction (EF). Results showed that there was no difference in these functional parameters for both the subjects and controls. This suggests normal LV contractility in children with SCA despite the increased dimensions of the LV. Lester [4
] found that resting parameters of ventricular function based on FS, EF and the mean velocity of circumferential fibre shortening (which we were limited in studying) were comparable to that of the controls.
The functional parameters (EF and FS) did not show any correlation with age. This has also been reported by other workers [4
]. From this findings it can be deduced that percentage of blood ejected from the heart and the degree of cardiac contractility
remains the same in spite of a marked increase in LV size during normal growth and development.
There was a significant relationship between the direct ECHO parameters and the BSA. Other workers have reported similar findings [4
]. The functional parameters however were independent of the BSA. This implies that the percentage of blood ejected and the degree of cardiac contractility with each heart beat remains the same irrespective of the BSA.
With respect to the haematocrit level, the value obtained in the SCA subjects was significantly lower than that obtained in the healthy AA controls. This was not unexpected because of the chronic anaemia associated with SCA. However, we found no correlation between the haematocrit levels, and the ECHO parameters and measures of left ventricular systolic function in both the SCA and the control groups. This is similar to the findings of Omokhodion et al. [9
] and Animasaun et al. [13
] that carried out similar studies in western Nigeria as well as Cipollotti et al. [6
] and Chung et al. [35
]. However, Taksande et al. [5
] reported significant increase in LV dimensions and mass proportional to the degree of anaemia. Also, Covitz et al. [25
] reported that the degree of dilatation
was significantly associated with the severity of anaemia.
The human heart is indeed a three-dimensional structure thus; where the resources are available for 3-D echocardiography
volumetric indices such as LA volume and LA volume index, (LAVi) as well as LV volumetric analyses should be undertaken. Our study was limited in this regards as well as the fact that we embarked on this study from a single centre.
It has been suggested that the heart is affected as part of the disease process in patients with SCA as a result of the chronic LV volume overload and sustained high cardiac output caused by the severe long standing anaemia [4
]. However, this study and previous investigations have consistently failed to show impairment in systolic performance in children with SCA. Thus, diastolic dysfunction
remains the alternative explanation for the cardiac symptoms in SCA [13
]. Thus, early and routine echocardiography in children with sickle cell anaemia would be of great benefit in the identification of structural abnormalities and this may enhance early interventions which may prevent such systolic dysfunctions that have being noted in adults with SCA.