Indian Pediatrics 1999;36: 991-998

Demasking of subclinical left ventricular dysfunction in anemic children

R.K. Kapoor, Lokendra Singh, S. Mehrotra**, P.K. Mishra and Mahesh Chandra**

From the Departments of Pediatrics and Medicine**, King George's Medical College, Lucknow 226 003, UP, India.
Reprint requests: Dr. R.K. Kapoor, 34, Khun-Khun Ji Road, Chowk, Lucknow 226 003, UP. India.
Manuscript received: June 2, 1998; Initial review completed: August 3, 1998; Revision accepted: April 9, 1999.


Objective: To study subclinical left ventricular dysfunction in anemic children. Setting: Hospital. Subjects: The study population consisted of 52 cases of anemia (16 mild, 14 moderate, 22 severe) and 20 normal age and height matched children aged between 7-12 years. Methods: These children were subjected to Echocardiography on Ascuson XP model using 3.5 MHz Transducer during rest and immediately after maximum tolerated exercise on Quniton Model Q-5000 treadmill using modified Naughton protocol. Left ventricular end diastolic dimensions, left ventricular systolic dimension, fractional shortening, left ventricular end diastolic volume, systolic volume, stroke volume and ejection fraction were studied on M-mode echocardiography, and E/A ratio on doppler mode. Results: Significant differences were observed in resting heart rate, gain in heart rate at peak exercise compared to basal values and double product, total exercise duration and metabolic equivalents at peak exercise in controls and anemic subjects. Left ventricular dysfunction was present in all severely anemic subjects after maximum tolerated exercise on treadmill. The only evidence of left ventricular diastolic dysfunction was in form of decreased left ventricular end diastolic volume after exercise in moderate and severely anemic subjects. Conclusions: Exercise is helpful in demasking subtle left ventricular dysfunctions in anemic subjects that are not detected during rest.

Key words: Anemia, Echocardiography, Tread mill.

 

Cardiac dilatation and hypertrophy are known to be associated with chronic  anemia(1). Anemia is the most common disease that may increase the cardiac output at rest. Chronic anemia in man usually increases the cardiac output, when hemoglobin level is <7g/dl but significant cardiac enlargement occurs only with an extreme reduction in hemoglobin (<4g/dl). The clinical findings of a hyperkinetic state in anemia, although frequently striking can be rapidly reversed by partial correction of the anemia in almost every instance. Circulatory congestion similar to that seen in congestive heart failure is an infrequent but serious complication of severe anemia(2).

Different studies have reported the high prevalence of anemia in young children in India(3). Anemia has a negative impact on physical work capacity in different age groups as measured by changes in maximum oxygen uptake and other metabolic parameters(4-7).

Most of the cardiac dysfunction is due to abnormalities of the left heart. Thus clinical evaluation of cardiac functions predominantly involves assessment of the performance of left ventricle. Cardiac function can be evaluated at several level of integration(8-11): (i) Myocar-dial function; (ii) Left ventricular pump perfor-mance; and (iii) Integrated cardiac output.

The pump performance of left  ventricle depends upon its ability to fill (diastolic performance) and to empty (systolic perfor-mance). Left ventricular systolic performance can be quantified as the left ventricular ejection fraction. An operational definition of systolic dysfunction is an ejection fraction of £50%(12). The treadmill has been widely used in the testing of exercise fitness since only ability to walk is required, numerous gradation of exercise level can be achieved and extensive standards have been developed. In children the main use of treadmill has been in assessment of exercise performance following repair of various congenital heart defects(13,14) and in assessing exercise capacity in various valvular heart defects(15).

Studies are available on exercise induced cardiac dysfunctions in patients in sickle cell anemia(16). But since sickle cell anemia is associated with cardiomegaly and cardio-myopathy, cardiac dysfunction occurs early in patients with sickle cell anemia. There are also recent echocardiographic studies on cardiac dysfunction in children with end stage renal diseases. However, end stage renal disease is associated with uremic cardiomyopathy and hypertension besides anemia that affect cardiac performance(17,18). The present study was undertaken with a view to evaluate the exercise induced cardiac dysfunction in anemic children.

Subjects and Methods

The present study was conducted on 52 anemic children (irrespective of cause of anemia) aged between 7-12 years, either admitted in Pediatric ward, or attending the Out Patient Department of Pediatrics, K.G.'s Medical College, Lucknow or studying in various schools in Lucknow. Twenty normal age and height matched school children served as controls.

The study population was subjected to detailed history and relevant general and physical examination. Body surface area was calculated from standard normograms using height and weight. The diagnosis of anemia was made by clinical assessment and hemoglobin estimation by cyanmethemoglobin method. A cut off criteria for diagnosis of anemia was taken as hemoglobin level <12 g/dl. Children were classified for severity of anemia as follows: (i) Mild - 10-12 g/dl; (ii) Moderate - 7-9.9 g/dl; and (iii) Severe - <7 g/dl.

Children with conditions like rheumatic or congenital heart disease, hypertension, bron-chial asthma, physical handicap, mental retardation, thyrotoxicity, any acute febrile illness, and severe malnutrition were excluded from the present study.

The selected subjects were subjected to echocardiography after 12 hours of rest on Ascuson-XP-Model using 3.5 MHz transducer. All measurements were taken according to American Society of Echocardiographists (ASE) recommendations. These children were then subjected to maximum tolerated exercise on treadmill. End point of exercise was refusal by the child to exercise further on account of fatigue. Subsequently, immediate post treadmill echocardiography was performed.

The following parameters were measured and analyzed on Echocardiography: (i) Left ventricular end diastolic dimensions; (ii) Left ventricular systolic dimensions; (iii) Fractional shortening; (iv) Left ventricular end diastolic volume; (v) Left ventricular systolic volume; (vi) Stroke volume; (vii)Ejection fraction; and (viii) E/A ratio. The following parameters were measured and analyzed on treadmill. (i) Heart rate; (ii) Blood pressure; (iii) Double product (HR “ BP); (iv) Exercise duration; (v) Metabolic equivalents; and (vi) ECG changes.

 

Results

The baseline data including age, weight, height and body surface area of 72 (52 male, 20 females) study subjects are depicted in Table I. Subjects were matched with each other for age and height, but body weight and body surface area differed signficantly. Out of 52 anemic, 48 were due to nutritional causes, four were due to various other causes but in these cases nutritional factors of causation were also present. No other deficiency disorder could be detected in cases.

Table I__Summary of Baseline Data.

Parameter Control
(n = 20)
(Mean ± SD)
Mild anemia
(n = 16)
(Mean ± SD)
Moderate anemia
(n = 14)
(Mean ± SD)
Severe anemia
(n = 22)
(Mean ± SD)
Age (Years) 9.4 ± 1.60 9.0 ± 1.63 9.5 ± 1.50 9.8 ± 1.63
Weight* (kg) 29.18 ± 4.28 26.10 ± 2.20 24.60 ± 4.24 23.50 ± 4.90

Height (cm)

130.5 ± 7.38 128 ± 7.68 123 ± 9.07 127.10 ± 7.98

Body surface (m2)

0.98 ± 0.06 0.94 ± 0.11 0.95 ± 0.05 0.88 ± 0.12

* p <0.01.

The results of exercise testing on the subejcts are summarized in Table II.

Table II__Values of Selected Parameters During Graded Treadmill Exercise.

Parameter Control
(n = 20)
(Mean ± SD)
Mild anemia
(n = 16)
(Mean ± SD)
Moderate anemia (n = 14)
(Mean ± SD)
Severe anemia
(n = 22)
(Mean ± SD)

Heart Rate (per min)

Resting*

96.78 ± 22.00 112.50 ± 18.36 110.50 ± 13.47 114.80 ± 17.30
Peak 179.64 ± 20.63 171 ± 13.47 168.85 ± 14.57 166.20 ± 22.98
Gain at peak excercise* 84.90 ± 20.36 57.78 ± 13.90 49.01 ± 16.07 42.26 ± 8.42

1 minute recovery

118.76 ± 14.34 114.46 ± 15.25 115.86 ± 15.62 122.00 ± 25.26
Systolic Blood Pressure . . . .

Resting

104.46 ± 11.31 104.20 ± 7.25 104.86 ± 6.24 108.80 ± 6.49
Peak excercise 114.36 ± 9.29 116.00 ± 7.22 116.43 ± 4.95 116.40 ± 6.54
Gain at peak excercise 10.16 ± 5.20 11.80 ± 3.45 10.61 ± 5.23 7.60 ± 2.79
Recovery 1 minute 109.30 ± 8.26 112.83 ± 6.60 110.46 ± 3.90 110.20 ± 5.85
.. . . . .

Double Product(DP)

. . . .

(in beats mm Hg)

. . . .

Resting 

10.47 ± 2.96 11.68 ± 2.03 11.28 ± 2.13 12.58 ± 2.60
Peak excercise 18.14 ± 3.28 17.68 ± 1.64 17.20 ± 1.90 16.90 ± 3.46
Gain at peak excersice* 7.69 ± 0.95 5.96 ± 1.01 5.94 ± 2.00 4.33 ± 1.76

Recovery 1 minute

12.04 ± 1.65 13.15 ± 1.96 12.87 ± 2.20 14.89 ± 3.58
Exercise duration* (min) 13.64 ± 1.26 8.97 ± 0.48 6.97 ± 1.44 3.45 ± 1.30
METS Achived* 6.94 ± 0.68 4.45 ± 0.64 4.30 ± 0.73 2.28 ± 0.37

* p <0.001 for comparison of each of the three grades of anemia with controls. 

There was significant difference in resting heart rate in four groups. The heart rate at peak exercise did not differ significantly, but gain in heart rate at peak exercise was significant (p <0.001). BP response did not reveal significant difference in any of the study groups. Double product response to graded treadmill exercise was similar to heart rate response, with a significant gain during peak exercise in normal children compared to anemic children (p <0.001). The control group exercised for significantly more duration than mild, moderate and severely anemic children. The values of metabolic  equivalents (METS) achieved during peak exercise were significantly higher in normal children compared to anemic groups according to severity of anemia (p <0.001). No significant ECG change was observed in any of the study group on maximal exercise.

Left Ventricular Dimensions

The results of echocardiography during rest and immediately after exercise are summarized in Table III. There was significant difference between left ventricular end diastolic dimensions between control and mild, moderate and severe anemia groups (p <0.001).

Table III__Values of Selected Parameters on Echocardiography

Parameter

Control (n = 20) Mild anemia (n = 16) Moderate anemia (n=14) Severe anemia (n = 22)
PreEx
(Mean±SD)
Post Ex
Mean±SD)
Pre Ex
(Mean±SD)
Post Ex
(Mean±SD)
Pre Ex
(Mean±SD)
Post Ex
(Mean±SD)
Pre Ex
(Mean±SD)
Post Ex
(Mean±SD)
Heart rate 96.78±
22.00
179.64 ± 20.63 112.50 ± 18.36 171.00 ± 13.47 110.50 ± 13.47 168.05 ± 14.57 114.80 ± 17.30 166.20 ± 21.98

LVEDV (cm/m2)

3.17 ±
0.45
3.73 ±
0.48
3.84 ±
0.62
3.77 ±
0.59
4.16 ±
0.56
4.02 ± 0.58 4.59 ± 0.68 4.38 ±
0.56

LVSD (cm/m2)

2.19 ±
0.39
2.18 ±
0.52
2.57 ±
0.38
2.50 ±
0.16
2.66 ±
0.43
2.53 ± 0.68 2.95 ± 0.36 3.51 ±
0.41
FS (%) 30.9 ±
2.13
41.5 ±
4.3 
33.0 ±
2.16
33.6 ±
4.6
38.45 ± 3.36 36.06 ± 2.80 35.72 ± 5.9 20.31 ±
5.2

LVEDV (ml/m2)

40.00 ± 8.60 58.9 ±
4.06
60.8 ±
3.86
63.1 ±
4.17
68.50 ± 9.16 51.50 ± 6.83 96.8 ± 2.31 86.8 ±
3.86
SV (Systolicml/m2) 16.0 ±
8.12
16.0 ±
8.12
17.0 ± 3.16 22.8 ±
2.84
23.10 ± 2.38 20.05 ± 3.01 43.6 ± 3.86 56.6 ±
4.16
Stroke
volume (ml/m2)
24.0 ±
6.36
42.9 ±
4.67
43.8 ±
2.36
40.4 ±
1.96
50.4 ±
2.16 
30.6 ± 1.68 53.30 ± 2.16 31.50 ± 1.28
EF (%) 60.0 ±
4.60
73.06 ± 8.34 72.01 ± 8.65 64.08 ± 3.16 73.72 ± 7.36 59.41 ± 4.36 53.06 ± 6.86 36.29 ± 4.38
E/A 1.74 ±
0.68
1.30 ±
0.81
1.91 ±
0.71
1.64 ±
0.72
2.11 ±
0.62
1.90 ± 0.48 2.36 ± 0.72 2.25 ±
1.01

In control group there was a significant increase in left ventricular end diastolic dimension after exercise, but change in other groups was not significant. Left ventricular systolic dimensions were significantly higher in patients with anemia compared to controls; the maximum values being for patients with severe anemia. Post exercise changes were not significant for various groups except for patients with severe anemia in whom left ventricular systolic dimensions were increased significantly after exercise (p <0.001).

Fractional shortening values were within normal range for various groups during rest (30-40%). After exercise, fractional shortening values increased for controls but there was no significant change in patients with mild or moderate anemia groups. For patients with severe anemia, value decreased significantly after exercise (p <0.001).

Left Ventricular Volume

The left ventricular end diastolic volumes were significantly more in patients with anemia, maximum values being for patients with severe anemia (p <0.001). After exercise there was significant increase in left ventricular end diastolic volume in controls. There was no change in patients with mild anemia and a significant decrease in patients with moderate and severe anemia. The left ventricular systolic volumes were significantly more in patients with severe anemia (p <0.001) and there was very significant increase in LV systolic volume after exercise in patients with severe anemia (p <0.001).

The stroke volume values were significantly higher in patients with various groups of anemia compared with controls. After exercise the stroke volume increased significantly in controls. However, there was a very significant decrease in patiens with moderate and severe anemia (p <0.001).

Ejection fraction (EF) response (the best indicator of left ventricular systolic function) was in normal ranges in various study groups. But after exercise there was significant increase in control groups. In patients with mild and moderate anemia, their value was lower as compared to pre-exercise value, but values were within normal range (>50%). But in patients with severe anemia, EF decreased very significantly after exercise (p <0.001). E/A ratio (the best indicator of LV diastolic dysfunction) was within normal range in all study group before and after exercise.

Discussion

In the present study the values of resting heart rates were significantly more in anemic children as compared to controls. But the heart rate response to exercise was less in anemic children as compared to controls, i.e., the gain in heart rate at peak exercise was significantly less in anemic children. These findings can be explained on the basis of cardiac reserve which is already depleted in anemic children which results in higher resting heart rate, less gain in heart rate at peak exercise and prolonged recovery time(6). The blood pressure response to exercise in anemic children was similar to that occuring in healthy subjects in the present as well as earlier studies(6,18).

Myocardial oxygen uptake reflecting myocardial oxygen consumption can be estimated during exercise testing by the product of heart rate and systolic blood pressure, i.e., double product, also called modified tension time index. The index in the present study behaved similar to the heart rate response. At peak exercise, the gain in double product was significantly less in anemia than in healthy children. These findings can again be explained by the depleted cardiac reserve in anemic children. We also observed that the reduced gain in double product in peak exercise was related to degree of anemia.

We did not find any evidence of electrical instability during exercise or recovery in children with anemia indicating that in presence of anemia with normal heart, exercise does not produce myocardial ischemia implying that these subjects may not be restricted for outdoor activities. Other workers also found no electrical instability in their study in anemic children(6,18).

We also analyzed metabolic equivalent (MET) which is unit of oxygen uptake (3.5 ml O2/kg/min). In the present study we found that anemic children achieved significantly less METS as compared to controls. This parameter also correlated directly to the degree of anemia. The lower degree of METS achieved in anemic children may be related to skeletal muscle exhausation rather than reduced cardiac reserve, as also evidenced by decreased exer-cise duration in anemic children. Similar results, although with different methodology were also reported by other authors(5,19,20).

There was significant increase in left ventricular end diastolic and systolic dimen-sions in children with anemia, indicating that left ventricular enlargement occurred in chronic anemia even with mild degree of anemia. Immediately after exercise there was no significant change in left ventricular end dias-tolic or systolic dimensions indicating that there was no significant diastolic dysfunction in any study group.

Fractional shortening was within normal range in all study groups during rest, however values were somewhat higher in children with anemia, indicating normal response to anemia. But after exercise, there was significant increase in fractional shortening in control group but in patients, with severe anemia there was a marked decrease. This finding indicates that exercise may disclose the subtle cardiac dysfunction in anemic children, that was not present during rest.

Left ventricular end diastolic volume and systolic volume were also significantly more in patients with moderate and severe anemia. However, overall stroke volume was also higher in patients with anemia indicating that increased cardiac output in anemia is mainly due to increased stroke volume. After exercise, stroke volume increased significantly in control groups but there was a decrease after exercise in patients with anemia indicating left ventricular systolic dysfunction after exercise in anemic subjects.

Ejection fraction during rest was within normal range in all study groups, although values were lower in patients with severe anemia. After exercise there was marked increase in ejection fraction in control group. However, there was significant decrease in ejection fraction in patients with moderate and severe anemia indicating poor left ventricular systolic function after exercise due to decreased myocardial contractility.

E/A ratio the most sensitive index of LV diastolic function was within normal range in all study groups before and after exercise indicating that there was no significant diastolic dysfunction in any study group during rest and after exercise.

To conclude, in the present study there was no significant systolic or diastolic dysfunction in any study groups during rest but after exercise there was significant systolic dys-function in all severely anemic subjects.

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