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Systolic time intervals in chronic anemia
Systolic time intervals in chronic anemia A.K. Abdullah, M.B., B.S., M.S. (Med.), F.R.C.P. (C)* M.A. Siddiqui, M.D., M.R.C.P., M.R.C.P. (Edin)** M. Tajuddin, M.D., D.T.M. & H (Lond.)*** Aligarh,
India
It is well known that chronic anemia is associated with hemodynamic alterations like increased cardiac output and stroke volume, and decreased peripheral vascular resistance.' Characteristic changes in systolic time intervals are known to accompany alterations in various hemodynamic parameters.- Although hemodynamic studies in chronic anemia have been reported by several investigators,^ ^ there is only one report of systolic time intervals in chronic anemia.'" Systolic time intervals measured by non-invasive techniques have been shown to be a convenient means of evaluation of myocardial performance.We have measured systolic time intervals in patients with chronic anemia in an attempt to determine the effect of chronic anemia on the phases of cardiac systole and on left ventricular performance. Materials and methods
Four groups of subjects were studied (Table I). All were free of any clinically evident underlying cardiovascular disease. Group I (Control group) consisted of 12 healthy subjects, aged 17 to 40 years (mean 28 ± 7 years) having hemoglobin concentration of 12 to 15 Gm. per cent (Mean 13.2 ± 1.2 Gm. per cent). Groups II, III, and IV (total 32 cases) were patients with anemia of at least two months duration as estimated by hisProm the Department of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, U.P. India. Received for publication Apr. 30, 1976. Accepted for publication June 15, 1976. Reprint requests: A. K. Abdullah, Department of Medicine, Jawaharlal Nehru Medical College, Ahgarh Muslim University, Aligarh, 202 001, U.P. India. •Reader in Medicine, Jawaharlal Nehru Medical College. "Professor of Medicine, Jawaharlal Nehru Medical College. ••"Professor of Medicine and Head, Department of Medicine, Jawaharlal Nehru Medical College.
September, 1977, Vol. 94, No. 3, pp. 287-291
tory. Anemia was due to ankylostomiasis in 15 cases, post-partum in 7 cases, and due to varied etiology in 10 cases. Group II (mild anemia) included 15 cases, aged 13 to 66 years (mean 38 ± 17 years) had hemoglobin concentration ranging between 7 to 11.8 Gm. per cent (mean 10.1 ± 1.3 Gm. per cent). Group III (severe anemia without congestive failure) consisted of 13 cases, aged, 14 to 70 years (mean 37 ± 17 years), with hemoglobin ranging between 1.5 to 6.0 Gm. per cent (mean 3.8 ± 1.7 Gm. per cent) and Group IV (severe anemia with congestive failure) included four cases, aged 22 to 60 years (mean 40 ± 18 years), with hemoglobin ranging between 1.4 to 6.0 Gm. per cent (mean 4.7 ± 2.2 Gm. per cent). Presence of peripheral pitting edema or hepatomegaly with jugular venous engorgement or persistent fine crepitations at lung bases with chest x-ray showing cardiomegaly and pulmonary vascular congestion were considered evidences of congestive failure. Systolic time intervals were determined from simultaneous recordings of phonocardiogram, electrocardiogram, and carotid pulse tracings obtained with subjects supine and resting, about 2 hours postprandial, using a Hewlett-Packard Model 1514B ECG/Phono system. Phonocardiogram was recorded by a contact microphone (HP 2105 A) from an area over the precordium which allowed best visualization of the initial high frequency vibrations of the second heart sounds. Carotid pulse tracing was obtained from the right carotid artery in the neck through a funnel-shaped pickup attached to an air-coupled pulse wave transducer (HP 21051 D). The electrocardiographic Lead I, II, or III (whichever showed best q waves) was recorded simultaneously. The paper speed was 50 m m . / s e c , with time markings at 20 msec. The recordings were
American Heart Journal
287
Abdullah, Siddiqui, and Tajuddin
Table I. The subjects included in the study
No. of cases Sex: Male Female Age (years): Range
Mean ± SD Hemoglobin (Gm. %): Range Mean ± SD Cause of anemia: Ankylostomiasis Postpartum Others
Group IVSevere anemia with congestive failure
Group I— Control
Group II— Mild anemia
Group IllSevere anemia without congestive failure
12
15
13
11 1
11 4
6 7
17-40 28 ± 7
13-66 38 ± 17
14-70 37 ± 17
22-60 40 ± 18
12.0 -15.0 13.2 ± 1.2
7.0-11.8 10.1 ± 1.3
1.5 - 6.0 3.8 ± 1.7
1.4 - 6.0 4.7 ± 2.2
7
6 5 2
2 2
— — —
— 8
1 3
Table il. Mean systoUc time intervals in the four groups of subjects studied
Group I (Control) Heart rate (per min.) PEPc (msec.) LVETc (msec.) QAjC (msec.) PEP/LVET
75 123 413 536 0.326
± ± ± ± ±
11 9 7 13 0.03
Group II (Mild anemia) 76 127 412 540 0.334
made with breath held at normal end-expiration, and measurements were made to the nearest 10 msec. Total electromechanical systole (QAj) was measured from the onset of q wave to the onset of first high-frequency vibrations of second heart sound, left ventricular ejection time (LVET) was measured from the onset of rapid upstroke to the trough of the dicrotic notch of carotid pulse tracing, and pre-ejection period (PEP) was calculated by subtracting LVET from QAj. These measurements were corrected for heart rate by a nomogram constructed by us (Fig. 1) based on the formulae of Weissler and Garrard." P E P / L V E T ratio was calculated from uncorrected measurements. Results
The findings of heart rate and rate-corrected PEP, LVET, and QA, (PEPc, LVETc, and QA,c, respectively) and P E P / L V E T ratio in each of the four groups of cases are summarized in Table IL 288
± + ± ± ±
26 8 12 14 0.04
Group III (Severe anemia without congestive failure) 88 112 429 541 0.270
± ± ± ± ±
17 14 25 24 0.05
Group IV (Severe anemia with congestive failure) 103 141 388 529 0.455
± ± ± ± ±
15 8 30 36 0.01
The heart rate in the control group (Group I) was 75 ± 11 beats per minute (mean ± S.D.). In the group with mild anemia (Group II) it was 76 ± 26 beats per minute which was not significantly different from the control group. In the groups of severe anemia without congestive failure (Group III) and with congestive failure (Group IV), the heart rate was significantly higher than in the control group (88 ± 17 beats per minute, P < 0.05; and 103 ± 15 beats per minute, P < 0.001, respectively). The mean PEPc in Group I was 123 ± 9 msec. In Group II it was 127 ± 8 msec, which was not significantly different from Group I. But in Group III it was 112 ± 14 msec, which was significantly less (P < 0.05), and in Group IV it was 141 ± 8 msec, which was significantly higher than in the control group (P < 0.001). The mean LVETc in the control group was 413 ± 7 msec. In Group II it was 412 ± 12 msec which was not significantly different from the control group, but in Group III (429 ± 25 msec.) September,
1977, Vol. 94, No. 3
Systolic
QA, LVET PEP 50 p- 250 p- 200 L 260
L 210
L27O
I
. 290
. 230
. 290
. 240
RATE
60
1 70
FOR
FOR
FOR
OA2
LVET
PEP
F
anemia
640
4
490
1
630
-i
480
4
620
1
4/0
4
6/0
4 460
4
600
J
450
4
5S0
4 440
4
5S0
4 4-30
4
570
4 420
4
560
4
4/0
4
^
550
i
400
4
/20 -_ -_
^ /60
-_
/50
1
M E- 120
250
. 300
in chronic
OAic LVETc PEPc 650 -. 500170 q HEART
220
time intervals
-_
120lr 260
310
M- no
-_ SO
/40
Z
110-
320
F M l o o t ""' F&M
270
rrl20
330
280
. 340
-
120
- i - 90
90
290
100
80- ^ 70
110-*-
4=-IOo"'1r
=-
80
E
40
350
300
360
310
9
540
4 390
4
370
320
-lE. 80 JO -f L
530
4 3i0
4
380
330
70-=E_
520
4
390
340
400
350
410
360
420
370
430
380
440 E. 450
-100
-110
'00jj- ,ol[:'° 50^
-120
iO •^--
50 J ^ " -130
QAic LVETc
-140
MF = Ms F =
QAt-i-2-l HR QA1+2OHR LVET +1-7 HR LVET + 1 6 HR
PEPc M & F= PEP + 0 4 HR
tZ/50
/30
//O
-
I
370
4
5/0
4 360
4
/OO -
500
4 350
4
^
490
4
340
4
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480
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4
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4 320 J
4
fo i
1 j - «0
390 E.400
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\
-_
•
460
4
3/0
i
•j
450
4 300
i
70 1
Fig. 1. Nomogram for correction of observed values of systolic time intervals for heart rate, based on the formulae of Weissler and Garrard. • To use the nomogram for correction of QA2, place a straight edge at the observed value of QA.^ on the "QA./' scale on the left side and the observed heart rate on the "heart rate for QA2" scale in the middle and read the rate-corrected QA, on the "QA-^c" scale on the right side. Similarly, for correction of observed LVET, use the scales labelled as "LVET," "Heart rate for LVET," and "LVETc," and for correction of observed P E P , use the scales " P E P , " "Heart rate for P E P , " and "PEPc." It should be noted that separate scales are provided for females and males for heart rate for QA,, and LVET, but the same scale is to be used for both sexes for heart rate for PEP. QAjC may also be calculated by adding LVETc and PEPc, thus providing a double-check on the readings of the nomogram.
it was significantly higher (P < 0.05), and in Group IV (388 ± 30 msec.) it was significantly less than in the control group (P < 0.001). There was marked variation in the findings among cases in Groups III and IV as indicated by large standard deviations in these two groups. The mean QA,c in the control group was American Heart Journal
536 ± 13 msec. In Group II (540 ± 14 msec.) and Group III (541 ± 24 msec.) it was not significantly different from the control group, but in Group IV (529 ± 36 msec.) it was significantly lesser than in the control group (P < 0.01). As in LVETc, there was wide variation in QA^c also among the cases in Groups III and IV. 289
Abdullah, Siddlqui, and Tajuddin The mean P E P / L V E T ratio was 0.326 ± 0.03 in the control group. In Group II (0.334 ± 0.04) it was not significantly different from the control group, but in Group III (0.270 ± 0.05) it was significantly less (P < 0.01), and in Group IV (0.455 ± 0.01) it was significantly higher than in the control group (P < 0.001). Discussion
Hemodynamic studies in resting subjects with chronic anemia by several investigators have established that there is no discernable hemodynamic abnormality in patients with mild anemia (hemoglobin above 7 Gm. per cent).' We found that systolic time intervals were also normal in such cases. When hemoglobin is less than 7 Gm. per cent, cardiac output is known to be increased mainly due to decreased peripheral vascular resistance causing increased speed of circulation and consequent increased venous return resulting in increased stroke volume.' Investigations designed to determine the effect of alterations in stroke volume on systolic time intervals have shown that increase in stroke volume due to enhanced ventricular filling is accompanied by decrease of P E P and increase of LVET while QA2 remains unaltered.- We found that in chronic severe anemia where cardiac output is known to be increased due to increased stroke volume, the pattern of systolic time intervals usually associated with increased stroke volume (i.e., decreased P E P , increased LVET, and decreased P E P / L V E T ratio) was found only when there was no congestive failure. In our cases of severe chronic anemia with congestive failure, the pattern of systolic time intervals was just the opposite, i.e., increased PEP, decreased LVET, and increased P E P / L V E T ratio. This pattern is usually found in heart failure with reduced cardiac output and stroke volume and is considered to be the result of impaired left ventricular performance.- The congestive failure in chronic anemia is a "high output failure" where although the cardiac output is higher than the normal, it is believed to be deficient relative to the needs of the body.' Thus in chronic anemia with congestive failure, where cardiac output may still be higher than normal, impairment of myocardial performance is clearly evident by the characteristic alterations of the systolic time intervals. Manchanda and colleagues' studied cases of
290
chronic severe anemia (hemoglobin < 6.5 Gm. per cent) without congestive failure and found no change in QA, or LVET but significant increase in P E P , and concluded that this represented depressed myocardial contractility or subclinical left ventricular failure. But in our cases of chronic severe anemia without congestive failure (our Group III), the P E P was reduced and LVET was increased. We found increased P E P only in our cases of chronic severe anemia with congestive failure (our Group IV), who, in addition, also had reduced LVET. We found wide variations in systolic time intervals in cases with severe anemia both with and without congestive failure. Although as groups these cases showed characteristic alterations, for any individual patient the systolic time intervals could not be predicted from hemoglobin levels. Such variability has been reported in hemodynamic measurements also.^ A possible explanation for this may be that myocardial performance in these cases is determined not only by the degree of anemia but also by such other factors as the state of hydration and nutrition of the patient and the presence of subclinical cardiovascular disease. Recently there has been great interest in the use of systolic time intervals for evaluations of left ventricular performance in many clinical situations.- Our study shows that chronic anemia can cause alterations in these measurements. Therefore hemoglobin levels of the subjects must also be taken into account while interpreting systolic time intervals. Summary
Systolic time intervals were measured noninvasively in 12 healthy control subjects (hemoglobin 12 to 15 Gm. per cent) and 32 cases of chronic anemia without underlying cardiovascular disease. It was found that in mild anemia (hemoglobin above 7 Gm. per cent), where cardiac output is known to be normal, the systolic time intervals were also normal. In severe anemia (hemoglobin below 7 Gm. per cent), where cardiac output is known to be high, the systolic time intervals showed the pattern usually associated with high cardiac output, i.e., increased left ventricular ejection time (LVET) and decreased pre-ejection period (PEP) and P E P / L V E T ratio, only when congestive failure was absent. In
September, 1977, Vol. 94, No. 3
Systolic time intervals in chronic
severe anemia with congestive failure, the LVET was decreased, and P E P and P E P / L V E T ratio were increased—the pattern associated with impaired myocardial performance, even though cardiac output is known to be high in such cases also. REFERENCES 1. 2.
Friedberg, C. K.: The heart and circulation in anemia, in Diseases of the heart, 3rd ed., Philadelphia and London, 1966, W.B. Saunders Company, chap. 44, p. 1678. Weissler, A. M., Lewis, R. P., and Leighton, R. F.: The systolic time intervals as a measure of left ventricular
American Heart Journal
anemia
performance in man, chapter 6 in Progress in cardiology, vol. I, editors P. N. Yu and J. F. Goodwin, Philadelphia, 1972, Publishers Lea & Febiger, pp. 155-183. Graettinger, G. S., Parson, R. L., and Campbell, J. A.: A correlation of clinical and hemodynamic studies in patients with mild and severe anemia with and without congestive failure, Ann. Intern. Med. 58: 617, 1963. Roy, S. B., Bhatia, M. L., Mathur, V. S. and Virmani, S.: Hemodynamic effects of chronic severe anemia, Circulation 28; 346, 1963. Manchanda, S. C , Bansal, R., Soni, V., and Roy, S. B.: Systolic time intervals in chronic severe anemia, Indian Heart J. 26: 32, 1974. Weissler, A. M., and Garrard, C. L., Jr.: Systolic time intervals in cardiac disease. Part I, Mod. Concepts Cardiovasc. Dis. 4 0 : 1, 1971.
291
India
It is well known that chronic anemia is associated with hemodynamic alterations like increased cardiac output and stroke volume, and decreased peripheral vascular resistance.' Characteristic changes in systolic time intervals are known to accompany alterations in various hemodynamic parameters.- Although hemodynamic studies in chronic anemia have been reported by several investigators,^ ^ there is only one report of systolic time intervals in chronic anemia.'" Systolic time intervals measured by non-invasive techniques have been shown to be a convenient means of evaluation of myocardial performance.We have measured systolic time intervals in patients with chronic anemia in an attempt to determine the effect of chronic anemia on the phases of cardiac systole and on left ventricular performance. Materials and methods
Four groups of subjects were studied (Table I). All were free of any clinically evident underlying cardiovascular disease. Group I (Control group) consisted of 12 healthy subjects, aged 17 to 40 years (mean 28 ± 7 years) having hemoglobin concentration of 12 to 15 Gm. per cent (Mean 13.2 ± 1.2 Gm. per cent). Groups II, III, and IV (total 32 cases) were patients with anemia of at least two months duration as estimated by hisProm the Department of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, U.P. India. Received for publication Apr. 30, 1976. Accepted for publication June 15, 1976. Reprint requests: A. K. Abdullah, Department of Medicine, Jawaharlal Nehru Medical College, Ahgarh Muslim University, Aligarh, 202 001, U.P. India. •Reader in Medicine, Jawaharlal Nehru Medical College. "Professor of Medicine, Jawaharlal Nehru Medical College. ••"Professor of Medicine and Head, Department of Medicine, Jawaharlal Nehru Medical College.
September, 1977, Vol. 94, No. 3, pp. 287-291
tory. Anemia was due to ankylostomiasis in 15 cases, post-partum in 7 cases, and due to varied etiology in 10 cases. Group II (mild anemia) included 15 cases, aged 13 to 66 years (mean 38 ± 17 years) had hemoglobin concentration ranging between 7 to 11.8 Gm. per cent (mean 10.1 ± 1.3 Gm. per cent). Group III (severe anemia without congestive failure) consisted of 13 cases, aged, 14 to 70 years (mean 37 ± 17 years), with hemoglobin ranging between 1.5 to 6.0 Gm. per cent (mean 3.8 ± 1.7 Gm. per cent) and Group IV (severe anemia with congestive failure) included four cases, aged 22 to 60 years (mean 40 ± 18 years), with hemoglobin ranging between 1.4 to 6.0 Gm. per cent (mean 4.7 ± 2.2 Gm. per cent). Presence of peripheral pitting edema or hepatomegaly with jugular venous engorgement or persistent fine crepitations at lung bases with chest x-ray showing cardiomegaly and pulmonary vascular congestion were considered evidences of congestive failure. Systolic time intervals were determined from simultaneous recordings of phonocardiogram, electrocardiogram, and carotid pulse tracings obtained with subjects supine and resting, about 2 hours postprandial, using a Hewlett-Packard Model 1514B ECG/Phono system. Phonocardiogram was recorded by a contact microphone (HP 2105 A) from an area over the precordium which allowed best visualization of the initial high frequency vibrations of the second heart sounds. Carotid pulse tracing was obtained from the right carotid artery in the neck through a funnel-shaped pickup attached to an air-coupled pulse wave transducer (HP 21051 D). The electrocardiographic Lead I, II, or III (whichever showed best q waves) was recorded simultaneously. The paper speed was 50 m m . / s e c , with time markings at 20 msec. The recordings were
American Heart Journal
287
Abdullah, Siddiqui, and Tajuddin
Table I. The subjects included in the study
No. of cases Sex: Male Female Age (years): Range
Mean ± SD Hemoglobin (Gm. %): Range Mean ± SD Cause of anemia: Ankylostomiasis Postpartum Others
Group IVSevere anemia with congestive failure
Group I— Control
Group II— Mild anemia
Group IllSevere anemia without congestive failure
12
15
13
11 1
11 4
6 7
17-40 28 ± 7
13-66 38 ± 17
14-70 37 ± 17
22-60 40 ± 18
12.0 -15.0 13.2 ± 1.2
7.0-11.8 10.1 ± 1.3
1.5 - 6.0 3.8 ± 1.7
1.4 - 6.0 4.7 ± 2.2
7
6 5 2
2 2
— — —
— 8
1 3
Table il. Mean systoUc time intervals in the four groups of subjects studied
Group I (Control) Heart rate (per min.) PEPc (msec.) LVETc (msec.) QAjC (msec.) PEP/LVET
75 123 413 536 0.326
± ± ± ± ±
11 9 7 13 0.03
Group II (Mild anemia) 76 127 412 540 0.334
made with breath held at normal end-expiration, and measurements were made to the nearest 10 msec. Total electromechanical systole (QAj) was measured from the onset of q wave to the onset of first high-frequency vibrations of second heart sound, left ventricular ejection time (LVET) was measured from the onset of rapid upstroke to the trough of the dicrotic notch of carotid pulse tracing, and pre-ejection period (PEP) was calculated by subtracting LVET from QAj. These measurements were corrected for heart rate by a nomogram constructed by us (Fig. 1) based on the formulae of Weissler and Garrard." P E P / L V E T ratio was calculated from uncorrected measurements. Results
The findings of heart rate and rate-corrected PEP, LVET, and QA, (PEPc, LVETc, and QA,c, respectively) and P E P / L V E T ratio in each of the four groups of cases are summarized in Table IL 288
± + ± ± ±
26 8 12 14 0.04
Group III (Severe anemia without congestive failure) 88 112 429 541 0.270
± ± ± ± ±
17 14 25 24 0.05
Group IV (Severe anemia with congestive failure) 103 141 388 529 0.455
± ± ± ± ±
15 8 30 36 0.01
The heart rate in the control group (Group I) was 75 ± 11 beats per minute (mean ± S.D.). In the group with mild anemia (Group II) it was 76 ± 26 beats per minute which was not significantly different from the control group. In the groups of severe anemia without congestive failure (Group III) and with congestive failure (Group IV), the heart rate was significantly higher than in the control group (88 ± 17 beats per minute, P < 0.05; and 103 ± 15 beats per minute, P < 0.001, respectively). The mean PEPc in Group I was 123 ± 9 msec. In Group II it was 127 ± 8 msec, which was not significantly different from Group I. But in Group III it was 112 ± 14 msec, which was significantly less (P < 0.05), and in Group IV it was 141 ± 8 msec, which was significantly higher than in the control group (P < 0.001). The mean LVETc in the control group was 413 ± 7 msec. In Group II it was 412 ± 12 msec which was not significantly different from the control group, but in Group III (429 ± 25 msec.) September,
1977, Vol. 94, No. 3
Systolic
QA, LVET PEP 50 p- 250 p- 200 L 260
L 210
L27O
I
. 290
. 230
. 290
. 240
RATE
60
1 70
FOR
FOR
FOR
OA2
LVET
PEP
F
anemia
640
4
490
1
630
-i
480
4
620
1
4/0
4
6/0
4 460
4
600
J
450
4
5S0
4 440
4
5S0
4 4-30
4
570
4 420
4
560
4
4/0
4
^
550
i
400
4
/20 -_ -_
^ /60
-_
/50
1
M E- 120
250
. 300
in chronic
OAic LVETc PEPc 650 -. 500170 q HEART
220
time intervals
-_
120lr 260
310
M- no
-_ SO
/40
Z
110-
320
F M l o o t ""' F&M
270
rrl20
330
280
. 340
-
120
- i - 90
90
290
100
80- ^ 70
110-*-
4=-IOo"'1r
=-
80
E
40
350
300
360
310
9
540
4 390
4
370
320
-lE. 80 JO -f L
530
4 3i0
4
380
330
70-=E_
520
4
390
340
400
350
410
360
420
370
430
380
440 E. 450
-100
-110
'00jj- ,ol[:'° 50^
-120
iO •^--
50 J ^ " -130
QAic LVETc
-140
MF = Ms F =
QAt-i-2-l HR QA1+2OHR LVET +1-7 HR LVET + 1 6 HR
PEPc M & F= PEP + 0 4 HR
tZ/50
/30
//O
-
I
370
4
5/0
4 360
4
/OO -
500
4 350
4
^
490
4
340
4
90 Z
480
-j 330
4
•j
470
4 320 J
4
fo i
1 j - «0
390 E.400
SO
\
-_
•
460
4
3/0
i
•j
450
4 300
i
70 1
Fig. 1. Nomogram for correction of observed values of systolic time intervals for heart rate, based on the formulae of Weissler and Garrard. • To use the nomogram for correction of QA2, place a straight edge at the observed value of QA.^ on the "QA./' scale on the left side and the observed heart rate on the "heart rate for QA2" scale in the middle and read the rate-corrected QA, on the "QA-^c" scale on the right side. Similarly, for correction of observed LVET, use the scales labelled as "LVET," "Heart rate for LVET," and "LVETc," and for correction of observed P E P , use the scales " P E P , " "Heart rate for P E P , " and "PEPc." It should be noted that separate scales are provided for females and males for heart rate for QA,, and LVET, but the same scale is to be used for both sexes for heart rate for PEP. QAjC may also be calculated by adding LVETc and PEPc, thus providing a double-check on the readings of the nomogram.
it was significantly higher (P < 0.05), and in Group IV (388 ± 30 msec.) it was significantly less than in the control group (P < 0.001). There was marked variation in the findings among cases in Groups III and IV as indicated by large standard deviations in these two groups. The mean QA,c in the control group was American Heart Journal
536 ± 13 msec. In Group II (540 ± 14 msec.) and Group III (541 ± 24 msec.) it was not significantly different from the control group, but in Group IV (529 ± 36 msec.) it was significantly lesser than in the control group (P < 0.01). As in LVETc, there was wide variation in QA^c also among the cases in Groups III and IV. 289
Abdullah, Siddlqui, and Tajuddin The mean P E P / L V E T ratio was 0.326 ± 0.03 in the control group. In Group II (0.334 ± 0.04) it was not significantly different from the control group, but in Group III (0.270 ± 0.05) it was significantly less (P < 0.01), and in Group IV (0.455 ± 0.01) it was significantly higher than in the control group (P < 0.001). Discussion
Hemodynamic studies in resting subjects with chronic anemia by several investigators have established that there is no discernable hemodynamic abnormality in patients with mild anemia (hemoglobin above 7 Gm. per cent).' We found that systolic time intervals were also normal in such cases. When hemoglobin is less than 7 Gm. per cent, cardiac output is known to be increased mainly due to decreased peripheral vascular resistance causing increased speed of circulation and consequent increased venous return resulting in increased stroke volume.' Investigations designed to determine the effect of alterations in stroke volume on systolic time intervals have shown that increase in stroke volume due to enhanced ventricular filling is accompanied by decrease of P E P and increase of LVET while QA2 remains unaltered.- We found that in chronic severe anemia where cardiac output is known to be increased due to increased stroke volume, the pattern of systolic time intervals usually associated with increased stroke volume (i.e., decreased P E P , increased LVET, and decreased P E P / L V E T ratio) was found only when there was no congestive failure. In our cases of severe chronic anemia with congestive failure, the pattern of systolic time intervals was just the opposite, i.e., increased PEP, decreased LVET, and increased P E P / L V E T ratio. This pattern is usually found in heart failure with reduced cardiac output and stroke volume and is considered to be the result of impaired left ventricular performance.- The congestive failure in chronic anemia is a "high output failure" where although the cardiac output is higher than the normal, it is believed to be deficient relative to the needs of the body.' Thus in chronic anemia with congestive failure, where cardiac output may still be higher than normal, impairment of myocardial performance is clearly evident by the characteristic alterations of the systolic time intervals. Manchanda and colleagues' studied cases of
290
chronic severe anemia (hemoglobin < 6.5 Gm. per cent) without congestive failure and found no change in QA, or LVET but significant increase in P E P , and concluded that this represented depressed myocardial contractility or subclinical left ventricular failure. But in our cases of chronic severe anemia without congestive failure (our Group III), the P E P was reduced and LVET was increased. We found increased P E P only in our cases of chronic severe anemia with congestive failure (our Group IV), who, in addition, also had reduced LVET. We found wide variations in systolic time intervals in cases with severe anemia both with and without congestive failure. Although as groups these cases showed characteristic alterations, for any individual patient the systolic time intervals could not be predicted from hemoglobin levels. Such variability has been reported in hemodynamic measurements also.^ A possible explanation for this may be that myocardial performance in these cases is determined not only by the degree of anemia but also by such other factors as the state of hydration and nutrition of the patient and the presence of subclinical cardiovascular disease. Recently there has been great interest in the use of systolic time intervals for evaluations of left ventricular performance in many clinical situations.- Our study shows that chronic anemia can cause alterations in these measurements. Therefore hemoglobin levels of the subjects must also be taken into account while interpreting systolic time intervals. Summary
Systolic time intervals were measured noninvasively in 12 healthy control subjects (hemoglobin 12 to 15 Gm. per cent) and 32 cases of chronic anemia without underlying cardiovascular disease. It was found that in mild anemia (hemoglobin above 7 Gm. per cent), where cardiac output is known to be normal, the systolic time intervals were also normal. In severe anemia (hemoglobin below 7 Gm. per cent), where cardiac output is known to be high, the systolic time intervals showed the pattern usually associated with high cardiac output, i.e., increased left ventricular ejection time (LVET) and decreased pre-ejection period (PEP) and P E P / L V E T ratio, only when congestive failure was absent. In
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Systolic time intervals in chronic
severe anemia with congestive failure, the LVET was decreased, and P E P and P E P / L V E T ratio were increased—the pattern associated with impaired myocardial performance, even though cardiac output is known to be high in such cases also. REFERENCES 1. 2.
Friedberg, C. K.: The heart and circulation in anemia, in Diseases of the heart, 3rd ed., Philadelphia and London, 1966, W.B. Saunders Company, chap. 44, p. 1678. Weissler, A. M., Lewis, R. P., and Leighton, R. F.: The systolic time intervals as a measure of left ventricular
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performance in man, chapter 6 in Progress in cardiology, vol. I, editors P. N. Yu and J. F. Goodwin, Philadelphia, 1972, Publishers Lea & Febiger, pp. 155-183. Graettinger, G. S., Parson, R. L., and Campbell, J. A.: A correlation of clinical and hemodynamic studies in patients with mild and severe anemia with and without congestive failure, Ann. Intern. Med. 58: 617, 1963. Roy, S. B., Bhatia, M. L., Mathur, V. S. and Virmani, S.: Hemodynamic effects of chronic severe anemia, Circulation 28; 346, 1963. Manchanda, S. C , Bansal, R., Soni, V., and Roy, S. B.: Systolic time intervals in chronic severe anemia, Indian Heart J. 26: 32, 1974. Weissler, A. M., and Garrard, C. L., Jr.: Systolic time intervals in cardiac disease. Part I, Mod. Concepts Cardiovasc. Dis. 4 0 : 1, 1971.
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