British Heart Journal, 1978, 40, 690-696
Left ventricular performance in children with homozygous sickle cell anaemial ALLAN H. REES2, MILTIADIS A. STEFADOUROS, WILLIAM B. STRONG, MAX D. MILLER, PRISCILLA GILMAN, JUDY A. RIGBY, AND JUDITH McFARLANE From the Department of Pediatrics, Section of Pediatric Cardiology, Medical College of Georgia, Augusta, Georgia, USA
SUMMARY Left ventricular performance was determined by echocardiography in 44 black children with homozygous sickle cell anaemia and a control group of 28 normal black children of comparable age. Statistically significant differences were observed between the children with sickle cell anaemia and the normal group in left ventricular ejection fraction (sickle cell anaemia group: 0-59 + 0.01 [mean + standard error of the mean] vs. normal group: 0-65 + 0.01), cardiac index (5.3 + 0 3 vs 4-2 + 0 3 1/min per i2), mean circumferential fibre shortening velocity (116 + 0 04 vs 1-31 + 0.03s-1) and the percentage of shortening of left ventricular minor axis dimension (32.5 + 1 vs 36-7 + 0.8). The children with sickle cell anaemia were divided into two groups according to the absence or presence of dyspnoea and/or fatigue on moderate effort; though both groups had the same degree of anaemia, significantly depressed left ventricular performance indices were observed only in the group of symptomatic patients. All asymptomatic children with sickle-cell anaemia had uncompromised left ventricular performance. These findings indicate that left ventricular dysfunction is present in a significantproportionof children with sickle cell anaemia. The extent of the left ventricular dysfunction, is not related to the degree of anaemia or the percentage of fetal haemoglobin. Since many of the symptoms, physical signs, and radiological findings of severe anaemia resemble those ofcongestive heart failure, echocardiographic examination of symptomatic children with homozygous sickle cell anaemia is useful in detecting the presence of left ventricular dysfunction. Children and adults with homozygous sickle cell with the tendency of the sickle cells to occlude small anaemia frequently present evidence of cardio- vessels in the systemic, pulmonary (Moser et al., vascular system abnormalities (Klinefelter, 1942; 1960), and coronary circulation (Oliveira and Winsor and Burch, 1945; Wintrobe, 1946; Shubin Gomez-Patino, 1963; Rubler and Fleischer, 1967) et al., 1960; Uzsoy, 1964; Ng et al., 1967). The may result in left ventricular dysfunction in the reduced haemoglobin content in conjunction with absence of other cardiac abnormalities. However the pulmonary dysfunction (Moser and Shea, probable, this hypothesis has not yet been ade1957; Moser et al., 1960; Femi-Pearse et al., 1970) quately documented (Lindsay et al., 1974). Recent observed in these subjects causes chronic arterial noninvasive studies have failed to identify left hypoxaemia (Jensen et al., 1957; Sproule et al., ventricular dysfunction in adults with sickle cell 1957) and a compensatory high cardiac output state anaemia (Gerry et al., 1976). This study was de(Brannon et al., 1945; Leight et al., 1954; Sproule signed to evaluate the performance of the left et al., 1958; Varat et al., 1972). It is postulated that ventricle in children with sickle cell anaemia. the excessive work load chronically imposed on the heart by the high cardiac output, in conjunction Subjects and methods 'This study was supported in part by a NIH grant. 2Present address: University of Louisville, Division of Pediatric Cardiology, Health Science Center, Louisville, Kentucky 40202, USA. Received for publication 10 May 1977
Forty-four black children, whose ages ranged from
2 to 14 (mean 8*6 ±0 4) years, with homozygous sickle cell anaemia documented by haemoglobin
electrophoresis (SS haemoglobin), and a control group of 28 randomly selected normal black
690
691
Left ventricular performance in children with homozygous sickle cell anaemia
children of comparable age (range 3 to 16, mean 7*8 ±0t7 years, P >005) had echocardiographic evaluation of left ventricular function. History, physical
examination, electrocardiogram, and chest x-ray were obtained on all patients. The following haematological data were also obtained: haemo-
Table 1 Clinical and noninvasive data of 44 patients with homozygous sickle cell anaemia Case
Age/sex
(Y)
%FHb HR
ET
BSA
Dd/m'
Ds/m'
CI
% AD
EF
Vcf
3-4 0-6 7-0 12-0 21-0 21-0 4-6 16-9 5-1
86 80 83 70 80 103 66 71 60
300 290 320 310 300 280 340 275 250
1-00 0-98 1-64 1-06 0-70 0-6b 1-37 0-96 0-76
47 40-8 31-7 42-4 61-4 62-1 36 4 46-8 50-0
28 26-5 20-1 28-3 38-5 42-4 218 30-2 34-2
6-7 4-0 4-6 4-1 6-8 7-5 43 4-7 3-2
40 35 37 33 37 32 40 35 32
0-68 0-62 0-64
1-35 121 1-14
-
6-3 9-5 6-7 9-4 8-9 9-4 7-2 9-6 6-8
0-60 0-65 0-58 0-68 0-63 0-58
1-07 1-24 1-13 1P18 1-29 1-26
24-7 1-7
8-2 0-5
10-2 2-6
78 4
296 9
1-01 0-11
46-5 3-4
30-0 2-4
5-1 0-5
35-7 1
0-63 0-01
1-21 0-03
18 24 21 18 29 26 21 20 24 25 24 23 24 25 23 30 21 29 28 25 19 25 26 21
6-5 7-8 6-9 6-5 7-4 7-5 7-2 7-2 7-8 8-3 8-0 74 7-6 8-4 7-3 9-6 7-2 7-4 8-8 86 6-3 8-3 8-5 7-2 7-8 79 6-7 8-1 10 0 10-1 94 6-9 7-1 7-5 6-9
3-0 6-0 4-0 4-0 5-0 1-0 3-4 9-0 4-7 7-5 70
107 106 80 101 103 80 90 127 82 91 82 115 95 100 83 88 86 133 100 68 90 88 73 110 80 60 96 115 79 75 74 70 100
260 260 300 250 260 300 270 230 280 280 290 260 300 300 320 230 280 250 270 290 300 290 300 255
0-82 0-84 0-94 0-88 0-88 1-08 1-09 0-54 0-86 0-96 0-88 0 69 0-71 1-16 1-10 1-12 0-70 0-72 0-84 1-12 0 70 0-96 0-98
29-2 40-4 29-7 27-2 26-1 27-7 25-6 35-1 38-3 33-3 26-1 36-2 35-2 28-4 20-5 25-0 35-7 38-8 30-9 26-7 40-2
63
290
1-34
30-6
95
270
0-88
44-3
43 6 35-8 30-1 32-6 32-2 33 0 26-1 24-6 32-9
6-4 9-7 4-5 7-1 6-0 7-5 7-3 6-2 6-6 5-8 4-8 7-1 6-8 5-9 2-8 3-5 8-5 8-9 6-3 40 59 5-0 3-4 5-3 3-7 3-4 6-1 6-2 3-8 3-1 3-6 3-2 3-5 1-6 40
39 32 33 43 41 42 43 37 31 30 41 34 37 31 36 30 43 32 37 35 31 30 29 22 21 29 26 23 27 25 28 20 23 20 26
0-66 0-59 0-60 0-71 0-69 0-70 0-71 0-64 0-58 0-57 0-69 0-61 0-65 0-57 0-63 0-56 0-71 0-58 0-64 0-62 0-57 0 56 0 55 0-45 0 44 0 54 0-51 0-46 0 53 0 49 0 54 0 43 0 47 0-42 0 50
1-48 1-23 1-11 1-72 1-58 1-41 1-59 1-60 1-12 1-09 1-42 1-31 1-25 1-04 1-13
1-00 0-71 1-06 1-06 0-92 0 90 1-21 1-26
47-5 59-5 44-6 47-7 44-3 48-1 44-9 55-5 55-8 47-9 44-3 55-0 56-3 41-3 32-1 35-7 62-8 56-9 48-8 41-0 57 9 45-8 41-8 52-5 49-4 45 0 591 46-2 41-5 43-4 45 0 41-3 34-1
91 3
280 4
0 93 0 03
47-1 1-3
32-0 09
5-4 03
316 1-2
0-58 0-01
1-14 0 05
< 0 05
NS
NS
NS
NS
NS
NS
NS
NS
88 3
283 4
0.95 003
47 1-3
31-6 09
5-3 03
32-5 1
0.59
1-16 004
CIT Hct (>05)
Hb
Group I 1 2 3 4 5 6 7 8 9
10 9 13 11 4 5 14 10 5
M M F M F M F M M
+ + -
+ -
Mean 9 ±SEM 1-2
17 27 19 29 26 27 23 30
Group 2 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44
Mean
10 7 10 7 7 9 12 2 8 7 9 4 7 9 14 12 7 5 6 8
10 10 9 5 8 10 5 10 9 8 9 13 12 11 8
M M M F M F M M M M M M F F F M M F F M M M F M M F F M F F F M M M F
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
24 24
19 24
30 30
28 21 21 22 21
8-5
23-8
sSEM 0 4
0(6
P (1 vs 2) NS
NS
7-8 0-2 NS
-
7-0 13-4 3-0 3-0 -
2-0 30 1-6 8-0 30 90 5-0 10-0 2-6 10-0 18-0 8-2
12-0 2-0 30 16-5 12-5 6-5 0-8 NS
290 300
290 235 290 310
290 300 300
0-78 0-87
32-2
29-5 41-0 39 0 32-0
1-30 1-54 1-27 1-36 1-20 1-02 1-02 0-98 0-86 0 73 0-96 0 90 0-96
0.95 0-80 0-98 0-67 0-78 0-68 0 95
Groups 1 +2 Mean
8-6
4SEM 0-4
24 *-6
7-9 0-2
7-3 09
0-01
CIT, cardiothoracic ratio; Hct, haematocrit (%); Hb, haemoglobin (g/dl); %FHb, per cent fetal haemoglobin; HR, heart rate (beats/min); ET, left ventricular ejection time (ms); BSA, body surface area (m'); Dd/m', left ventricular end-diastolic dimension index (mm/m'); Ds/m' left ventricular end-systolic dimension index (mm/m'); CI, cardiac index (1/min per m'); % AD, per cent of shortening of minor axis LV dimension during systole; EF, ejection fraction; Vcf, mean rate of circumferential fibre shortening (sL); SEM, standard error of the mean; M, male; F, female; NS, statistically insignificant difference.
692
A. Rees, M. Stefadouros, W. Strong, M. Miller, P. Gilman, J7. A. Rigby, and J7. McFarlane
globin, haematocrit and percentage of fetal haemoglobin. On the basis of symptomatology the patients with sickle cell anaemia were divided into two groups. Group 1 consisted of 9 patients who were completely asymptomatic. Group 2 consisted of 35 patients with dyspnoea and/or fatigue at rest or initiated (or aggravated) by ordinary physical activity. Only one patient of group 2 (case 44, Table 1) was receiving maintenance digitalis. Echocardiographic examination was performed by use of a Smith Kline Ekoline 20 ultrasonoscope interfaced with a Honeywell fiberoptic strip-chart recorder. A 2-25 MHz focused (5 cm) transducer with an active crystal diameter of 1-27 cm was used. The children were studied in the supine position and the transducer was positioned along the left sternal border at that intercostal space (3rd to 5th, usually the 4th), from which a strong mitral valve echo was visualised, with the transducer pointed perpendicularly to the chest wall with slight medial but no superior or inferior angulation (Popp et al., 1975). From this position, the transducer was slowly tilted in an inferior and lateral direction, until the echoes of the mitral valve were replaced by those of the chordae tendineae; at this level the echogram was recorded after minor adjustments in transducer angulation and/or gain control, aimed at providing optimal visualisation of the endocardial echoes from both the posterior left ventricular wall and the left side of the interventricular septum. The left ventricular end-diastolic dimension (Dd) was measured as the vertical distance between the left septal echo and the left ventricular endocardial echo at the onset of the QRS complex of the electrocardiogram (Meyer et al., 1975). The left ventricular end-systolic dimension (Ds) was measured at the point of maximal approximation of the interventricular septum and the posterior left ventricular wall. Using these echocardiographic dimensions, the percentage shortening in the echocardiographic minor dimension of the left ventricle was calculated as (Fortuin et al., 1972): % AD= (Dd-Ds) x 100/Dd and the normalised mean rate of circumferential fibre shortening was calculated as (Paraskos et al., 1971; Cooper et al., 1972; Quinones et al., 1974): mean Vcf (s-1)=(Dd-Ds)/ETxDd where ET was the left ventricular ejection time measured from the onset of the rapid upstroke to the nadir of the dicrotic notch of the external carotid pulse tracing. Echocardiographic estimation of the left ventricular end-diastolic volume was obtained using the following regression equation (Meyer et al., 1975): EDV= 19-2±+1458 Dd+0'62 Dd3
The left ventricular ejection fraction (EF) was estimated from the echocardiographic left ventricular dimensions (Dd, Ds) using the mathematical relation previously described by Meyer et al. (1975) As Ds2\ EF= 1- id 5-dd / As where the factor d= 0 9O iS the ratio of end-systolic/end-diastolic left ventricular major axis dimajor t mension corresponding to an assumed 10 per cent shortening of this axis. The product (EDV x EF), representig the stroke volume, was multipliedbytheheart rateto provide the cardiac output which was then indexed for body surface area. All measurements were averaged over five arrhythmia-free cardiac cycles. Student's t test for non-paired data was used for statistical comparison of the results between groups; all values are given as mean ± standard error of the mean. Correlation coefficient (r) analysis was carried out by the least square method. The level of statistical significance was set at P < 0.05.
mensiaspolic
antricumed
cent
Results Clinical, radiographic, haematological, and echocardiographic data for the two groups of patients with sickle cell anaemia arelisted in detail in Table 1. Statistical analysis of the mean values for the echocardiographic indices of left ventricular performance in the two groups of patients with sickle cel anaemia as well as in the group ofnormalcontro
subjects is presented in Table 2. As can be seen in Table 1, there was no significant difference in age, haemoglobin content, or perTable 2 Echocardiographic indices of left ventricular and sickle two groups performance 28 normal cell with children homozygous patients (1 and 2) of in anaemia
Dd/m'
CI
%AD
EF
(mm,/ml) p(Il/mn Normal 40 4 ±1-8 4 2 ±0 3 36-7±0-8 0-65 ±0 01 (n = 28) 1 46-5* ±3-4 5.1* ±0-5 35.7* ±1 0-63* ±0-01 Group
Vcf (s ') 1-31 +0 03 1-21* ±0-03
(n=9) Group 2 47-1+ ±13 54t ±0-3 31-6+1-2 0-58§ ±0-01 1-14t ±0-05
(n=35) Abbreviations; Same as in Table 1. All values are expressed as mean ±standard error of the>mean. difference in comparison with *Statsticsally insignificant (P 0-05) normal group or group 2.
tP < 0-01 in comparison with normal group. +P < 0-005 in comparison with normal group. §P < 0-001 in comparison with normal group.
693
Left ventricular performance in children with homozygous sickle cell anaemia
_
*
.
50 40
a40
0*35
35
~
__
_
N
20
: _
I
r
05
7
1
30
F
EF
NS
Left ventricular performance in children with homozygous sickle cell anaemial ALLAN H. REES2, MILTIADIS A. STEFADOUROS, WILLIAM B. STRONG, MAX D. MILLER, PRISCILLA GILMAN, JUDY A. RIGBY, AND JUDITH McFARLANE From the Department of Pediatrics, Section of Pediatric Cardiology, Medical College of Georgia, Augusta, Georgia, USA
SUMMARY Left ventricular performance was determined by echocardiography in 44 black children with homozygous sickle cell anaemia and a control group of 28 normal black children of comparable age. Statistically significant differences were observed between the children with sickle cell anaemia and the normal group in left ventricular ejection fraction (sickle cell anaemia group: 0-59 + 0.01 [mean + standard error of the mean] vs. normal group: 0-65 + 0.01), cardiac index (5.3 + 0 3 vs 4-2 + 0 3 1/min per i2), mean circumferential fibre shortening velocity (116 + 0 04 vs 1-31 + 0.03s-1) and the percentage of shortening of left ventricular minor axis dimension (32.5 + 1 vs 36-7 + 0.8). The children with sickle cell anaemia were divided into two groups according to the absence or presence of dyspnoea and/or fatigue on moderate effort; though both groups had the same degree of anaemia, significantly depressed left ventricular performance indices were observed only in the group of symptomatic patients. All asymptomatic children with sickle-cell anaemia had uncompromised left ventricular performance. These findings indicate that left ventricular dysfunction is present in a significantproportionof children with sickle cell anaemia. The extent of the left ventricular dysfunction, is not related to the degree of anaemia or the percentage of fetal haemoglobin. Since many of the symptoms, physical signs, and radiological findings of severe anaemia resemble those ofcongestive heart failure, echocardiographic examination of symptomatic children with homozygous sickle cell anaemia is useful in detecting the presence of left ventricular dysfunction. Children and adults with homozygous sickle cell with the tendency of the sickle cells to occlude small anaemia frequently present evidence of cardio- vessels in the systemic, pulmonary (Moser et al., vascular system abnormalities (Klinefelter, 1942; 1960), and coronary circulation (Oliveira and Winsor and Burch, 1945; Wintrobe, 1946; Shubin Gomez-Patino, 1963; Rubler and Fleischer, 1967) et al., 1960; Uzsoy, 1964; Ng et al., 1967). The may result in left ventricular dysfunction in the reduced haemoglobin content in conjunction with absence of other cardiac abnormalities. However the pulmonary dysfunction (Moser and Shea, probable, this hypothesis has not yet been ade1957; Moser et al., 1960; Femi-Pearse et al., 1970) quately documented (Lindsay et al., 1974). Recent observed in these subjects causes chronic arterial noninvasive studies have failed to identify left hypoxaemia (Jensen et al., 1957; Sproule et al., ventricular dysfunction in adults with sickle cell 1957) and a compensatory high cardiac output state anaemia (Gerry et al., 1976). This study was de(Brannon et al., 1945; Leight et al., 1954; Sproule signed to evaluate the performance of the left et al., 1958; Varat et al., 1972). It is postulated that ventricle in children with sickle cell anaemia. the excessive work load chronically imposed on the heart by the high cardiac output, in conjunction Subjects and methods 'This study was supported in part by a NIH grant. 2Present address: University of Louisville, Division of Pediatric Cardiology, Health Science Center, Louisville, Kentucky 40202, USA. Received for publication 10 May 1977
Forty-four black children, whose ages ranged from
2 to 14 (mean 8*6 ±0 4) years, with homozygous sickle cell anaemia documented by haemoglobin
electrophoresis (SS haemoglobin), and a control group of 28 randomly selected normal black
690
691
Left ventricular performance in children with homozygous sickle cell anaemia
children of comparable age (range 3 to 16, mean 7*8 ±0t7 years, P >005) had echocardiographic evaluation of left ventricular function. History, physical
examination, electrocardiogram, and chest x-ray were obtained on all patients. The following haematological data were also obtained: haemo-
Table 1 Clinical and noninvasive data of 44 patients with homozygous sickle cell anaemia Case
Age/sex
(Y)
%FHb HR
ET
BSA
Dd/m'
Ds/m'
CI
% AD
EF
Vcf
3-4 0-6 7-0 12-0 21-0 21-0 4-6 16-9 5-1
86 80 83 70 80 103 66 71 60
300 290 320 310 300 280 340 275 250
1-00 0-98 1-64 1-06 0-70 0-6b 1-37 0-96 0-76
47 40-8 31-7 42-4 61-4 62-1 36 4 46-8 50-0
28 26-5 20-1 28-3 38-5 42-4 218 30-2 34-2
6-7 4-0 4-6 4-1 6-8 7-5 43 4-7 3-2
40 35 37 33 37 32 40 35 32
0-68 0-62 0-64
1-35 121 1-14
-
6-3 9-5 6-7 9-4 8-9 9-4 7-2 9-6 6-8
0-60 0-65 0-58 0-68 0-63 0-58
1-07 1-24 1-13 1P18 1-29 1-26
24-7 1-7
8-2 0-5
10-2 2-6
78 4
296 9
1-01 0-11
46-5 3-4
30-0 2-4
5-1 0-5
35-7 1
0-63 0-01
1-21 0-03
18 24 21 18 29 26 21 20 24 25 24 23 24 25 23 30 21 29 28 25 19 25 26 21
6-5 7-8 6-9 6-5 7-4 7-5 7-2 7-2 7-8 8-3 8-0 74 7-6 8-4 7-3 9-6 7-2 7-4 8-8 86 6-3 8-3 8-5 7-2 7-8 79 6-7 8-1 10 0 10-1 94 6-9 7-1 7-5 6-9
3-0 6-0 4-0 4-0 5-0 1-0 3-4 9-0 4-7 7-5 70
107 106 80 101 103 80 90 127 82 91 82 115 95 100 83 88 86 133 100 68 90 88 73 110 80 60 96 115 79 75 74 70 100
260 260 300 250 260 300 270 230 280 280 290 260 300 300 320 230 280 250 270 290 300 290 300 255
0-82 0-84 0-94 0-88 0-88 1-08 1-09 0-54 0-86 0-96 0-88 0 69 0-71 1-16 1-10 1-12 0-70 0-72 0-84 1-12 0 70 0-96 0-98
29-2 40-4 29-7 27-2 26-1 27-7 25-6 35-1 38-3 33-3 26-1 36-2 35-2 28-4 20-5 25-0 35-7 38-8 30-9 26-7 40-2
63
290
1-34
30-6
95
270
0-88
44-3
43 6 35-8 30-1 32-6 32-2 33 0 26-1 24-6 32-9
6-4 9-7 4-5 7-1 6-0 7-5 7-3 6-2 6-6 5-8 4-8 7-1 6-8 5-9 2-8 3-5 8-5 8-9 6-3 40 59 5-0 3-4 5-3 3-7 3-4 6-1 6-2 3-8 3-1 3-6 3-2 3-5 1-6 40
39 32 33 43 41 42 43 37 31 30 41 34 37 31 36 30 43 32 37 35 31 30 29 22 21 29 26 23 27 25 28 20 23 20 26
0-66 0-59 0-60 0-71 0-69 0-70 0-71 0-64 0-58 0-57 0-69 0-61 0-65 0-57 0-63 0-56 0-71 0-58 0-64 0-62 0-57 0 56 0 55 0-45 0 44 0 54 0-51 0-46 0 53 0 49 0 54 0 43 0 47 0-42 0 50
1-48 1-23 1-11 1-72 1-58 1-41 1-59 1-60 1-12 1-09 1-42 1-31 1-25 1-04 1-13
1-00 0-71 1-06 1-06 0-92 0 90 1-21 1-26
47-5 59-5 44-6 47-7 44-3 48-1 44-9 55-5 55-8 47-9 44-3 55-0 56-3 41-3 32-1 35-7 62-8 56-9 48-8 41-0 57 9 45-8 41-8 52-5 49-4 45 0 591 46-2 41-5 43-4 45 0 41-3 34-1
91 3
280 4
0 93 0 03
47-1 1-3
32-0 09
5-4 03
316 1-2
0-58 0-01
1-14 0 05
< 0 05
NS
NS
NS
NS
NS
NS
NS
NS
88 3
283 4
0.95 003
47 1-3
31-6 09
5-3 03
32-5 1
0.59
1-16 004
CIT Hct (>05)
Hb
Group I 1 2 3 4 5 6 7 8 9
10 9 13 11 4 5 14 10 5
M M F M F M F M M
+ + -
+ -
Mean 9 ±SEM 1-2
17 27 19 29 26 27 23 30
Group 2 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44
Mean
10 7 10 7 7 9 12 2 8 7 9 4 7 9 14 12 7 5 6 8
10 10 9 5 8 10 5 10 9 8 9 13 12 11 8
M M M F M F M M M M M M F F F M M F F M M M F M M F F M F F F M M M F
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
24 24
19 24
30 30
28 21 21 22 21
8-5
23-8
sSEM 0 4
0(6
P (1 vs 2) NS
NS
7-8 0-2 NS
-
7-0 13-4 3-0 3-0 -
2-0 30 1-6 8-0 30 90 5-0 10-0 2-6 10-0 18-0 8-2
12-0 2-0 30 16-5 12-5 6-5 0-8 NS
290 300
290 235 290 310
290 300 300
0-78 0-87
32-2
29-5 41-0 39 0 32-0
1-30 1-54 1-27 1-36 1-20 1-02 1-02 0-98 0-86 0 73 0-96 0 90 0-96
0.95 0-80 0-98 0-67 0-78 0-68 0 95
Groups 1 +2 Mean
8-6
4SEM 0-4
24 *-6
7-9 0-2
7-3 09
0-01
CIT, cardiothoracic ratio; Hct, haematocrit (%); Hb, haemoglobin (g/dl); %FHb, per cent fetal haemoglobin; HR, heart rate (beats/min); ET, left ventricular ejection time (ms); BSA, body surface area (m'); Dd/m', left ventricular end-diastolic dimension index (mm/m'); Ds/m' left ventricular end-systolic dimension index (mm/m'); CI, cardiac index (1/min per m'); % AD, per cent of shortening of minor axis LV dimension during systole; EF, ejection fraction; Vcf, mean rate of circumferential fibre shortening (sL); SEM, standard error of the mean; M, male; F, female; NS, statistically insignificant difference.
692
A. Rees, M. Stefadouros, W. Strong, M. Miller, P. Gilman, J7. A. Rigby, and J7. McFarlane
globin, haematocrit and percentage of fetal haemoglobin. On the basis of symptomatology the patients with sickle cell anaemia were divided into two groups. Group 1 consisted of 9 patients who were completely asymptomatic. Group 2 consisted of 35 patients with dyspnoea and/or fatigue at rest or initiated (or aggravated) by ordinary physical activity. Only one patient of group 2 (case 44, Table 1) was receiving maintenance digitalis. Echocardiographic examination was performed by use of a Smith Kline Ekoline 20 ultrasonoscope interfaced with a Honeywell fiberoptic strip-chart recorder. A 2-25 MHz focused (5 cm) transducer with an active crystal diameter of 1-27 cm was used. The children were studied in the supine position and the transducer was positioned along the left sternal border at that intercostal space (3rd to 5th, usually the 4th), from which a strong mitral valve echo was visualised, with the transducer pointed perpendicularly to the chest wall with slight medial but no superior or inferior angulation (Popp et al., 1975). From this position, the transducer was slowly tilted in an inferior and lateral direction, until the echoes of the mitral valve were replaced by those of the chordae tendineae; at this level the echogram was recorded after minor adjustments in transducer angulation and/or gain control, aimed at providing optimal visualisation of the endocardial echoes from both the posterior left ventricular wall and the left side of the interventricular septum. The left ventricular end-diastolic dimension (Dd) was measured as the vertical distance between the left septal echo and the left ventricular endocardial echo at the onset of the QRS complex of the electrocardiogram (Meyer et al., 1975). The left ventricular end-systolic dimension (Ds) was measured at the point of maximal approximation of the interventricular septum and the posterior left ventricular wall. Using these echocardiographic dimensions, the percentage shortening in the echocardiographic minor dimension of the left ventricle was calculated as (Fortuin et al., 1972): % AD= (Dd-Ds) x 100/Dd and the normalised mean rate of circumferential fibre shortening was calculated as (Paraskos et al., 1971; Cooper et al., 1972; Quinones et al., 1974): mean Vcf (s-1)=(Dd-Ds)/ETxDd where ET was the left ventricular ejection time measured from the onset of the rapid upstroke to the nadir of the dicrotic notch of the external carotid pulse tracing. Echocardiographic estimation of the left ventricular end-diastolic volume was obtained using the following regression equation (Meyer et al., 1975): EDV= 19-2±+1458 Dd+0'62 Dd3
The left ventricular ejection fraction (EF) was estimated from the echocardiographic left ventricular dimensions (Dd, Ds) using the mathematical relation previously described by Meyer et al. (1975) As Ds2\ EF= 1- id 5-dd / As where the factor d= 0 9O iS the ratio of end-systolic/end-diastolic left ventricular major axis dimajor t mension corresponding to an assumed 10 per cent shortening of this axis. The product (EDV x EF), representig the stroke volume, was multipliedbytheheart rateto provide the cardiac output which was then indexed for body surface area. All measurements were averaged over five arrhythmia-free cardiac cycles. Student's t test for non-paired data was used for statistical comparison of the results between groups; all values are given as mean ± standard error of the mean. Correlation coefficient (r) analysis was carried out by the least square method. The level of statistical significance was set at P < 0.05.
mensiaspolic
antricumed
cent
Results Clinical, radiographic, haematological, and echocardiographic data for the two groups of patients with sickle cell anaemia arelisted in detail in Table 1. Statistical analysis of the mean values for the echocardiographic indices of left ventricular performance in the two groups of patients with sickle cel anaemia as well as in the group ofnormalcontro
subjects is presented in Table 2. As can be seen in Table 1, there was no significant difference in age, haemoglobin content, or perTable 2 Echocardiographic indices of left ventricular and sickle two groups performance 28 normal cell with children homozygous patients (1 and 2) of in anaemia
Dd/m'
CI
%AD
EF
(mm,/ml) p(Il/mn Normal 40 4 ±1-8 4 2 ±0 3 36-7±0-8 0-65 ±0 01 (n = 28) 1 46-5* ±3-4 5.1* ±0-5 35.7* ±1 0-63* ±0-01 Group
Vcf (s ') 1-31 +0 03 1-21* ±0-03
(n=9) Group 2 47-1+ ±13 54t ±0-3 31-6+1-2 0-58§ ±0-01 1-14t ±0-05
(n=35) Abbreviations; Same as in Table 1. All values are expressed as mean ±standard error of the>mean. difference in comparison with *Statsticsally insignificant (P 0-05) normal group or group 2.
tP < 0-01 in comparison with normal group. +P < 0-005 in comparison with normal group. §P < 0-001 in comparison with normal group.
693
Left ventricular performance in children with homozygous sickle cell anaemia
_
*
.
50 40
a40
0*35
35
~
__
_
N
20
: _
I
r
05
7
1
30
F
EF
NS
