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Left ventricular contraction pattern changes with age in normal adults
Left Ventricular Contraction Pattern Changes with Age in Normal Adults Birger Wandt, MD, Leif Bojo¨, MD, PhD, Liv Hatle, MD, PhD, and Bengt Wranne, MD, PhD, Karlstad and Linko¨ping, Sweden
Left ventricular ejection fraction is known to be unchanged or slightly increased with advancing age. This echocardiographic study, including 40 healthy subjects 18 to 70 years old, shows that this is a net effect of decreased contractions in the long axis and increased in the short axis. From age 18 to 70 years, the longitudinal shortening decreases by 20% (P < .001) and the short-axis diameter shortening increases by 18% (P 5 .012). Multiple regression analysis showed strong correlation to age for both shortand long-axis contractions and no significant addi-
Left ventricular systole involves both a shortening in the longitudinal axis of the ventricle and a reduction of the inner diameter in the short axis1-4 and a slight rotational movement about the long axis.2 During systole, the epicardial apex of the heart is relatively stationary, whereas the mitral ring moves toward the apex. During diastole it ascends away from the apex, toward the left atrium. This motion has been shown with cineroentgenography of calcified regions of the mitral ring,5,6 with cineangiography,2 with radiopaque markings in the heart after surgery2 and with echocardiography,7-13 with computed tomography,14 and with magnetic resonance imaging.15 A high correlation has been shown between the amplitude of the mitral ring motion and ejection fraction, assessed by radionuclide angiography or by left ventricular angiography in patients with severe congestive heart failure after dilated cardiomyopathy or myocardial infarction,7 in patients with acute myocardial infarction,16 in patients with coronary artery disease,17 and in consecutive patients who had both echocardiogram and radionuclide angiography within 2 days (category of patients not mentioned).18 Previous studies with radionuclide angiography have shown that left ventricular ejection fraction at rest in adults is unchanged From the Department of Clinical Physiology, Central Hospital, and the Department of Clinical Physiology, Linko¨ping University Hospital. Supported in part by Swedish Medical Research Council grant 9481 and the Swedish Heart Lung Foundation. Reprint requests: Birger Wandt, MD, Department of Clinical Physiology, Central Hospital, S-651 85 Karlstad, Sweden. Copyright © 1998 by the American Society of Echocardiography. 0894-7317/98 $5.00 1 0 27/1/91281
tional explicatory power when the variables systolic blood pressure, left ventricular wall thickness, heart rate, or sex were included. There was no significant correlation between diameter changes during the isovolumic phases and age. The findings have practical implications when calculating ejection fraction from M-mode measurements. Teichholz’s formula will overestimate ejection fraction in elderly subjects, and calculation of ejection fraction from mitral ring motion will overestimate it in young subjects. (J Am Soc Echocardiogr 1998;11:857-63.)
or slightly increased with advancing age.19-21 This does not exclude the possibility of changes in circumferential or longitudinal shortening with age. One aim of the this study was to investigate this possibility. Previous studies have shown that the length of the isovolumic relaxation period increases with increasing age and that the isovolumic contraction phase tends to lengthen slightly with advancing age.22,23 It is also well known that there is a change in left ventricular shape during the isovolumic contraction period, with an apex-to-base shortening and a circumferential elongation.11,24 It is not clear, however, whether there is also a change in ventricular shape during the isovolumic relaxation period. Another aim of this study, therefore, was to investigate whether changes in ventricular shape during the isovolumic relaxation phase can be established by parasternal and apical M-mode recordings and to investigate if the degree of changes in the shape during the isovolumic periods changes with age. Previous studies have shown that the lateral part of the mitral ring moves a longer distance than the septal part.9,25 This means that the ring “tilts” during the motion toward the apex. It is not previously known whether the degree of “tilting” changes with age. An additional aim of the study was therefore to investigate whether the “tilting” motion of the mitral ring increases with advancing age. Study Population Forty subjects, mainly hospital employees and relatives 18 to 70 years old, were studied; there were 17 857
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Table 1 Linear correlation between left ventricular systolic short-axis diameter reduction and age, systolic blood pressure, sex, heart rate, and some echocardiographic measures Tested variable
Age Left ventricular wall thickness Left ventricular end-diastolic diameter Mitral ring motion Systolic blood pressure Left ventricular end-systolic diameter Sex Heart rate
Correlation Level of coefficient significance
.39 .32 .29 2.24 .22 2.17 .16 .07
P 5 .012 P 5 .044 NS NS NS NS NS NS
NS, Not significant.
Figure 1 Parasternal M-mode recording of left ventricle and apical recording of mitral ring motion in 35-year-old healthy woman.
women and 23 men. They had no history of cardiac disease, normal findings on physical examination, and a normal resting electrocardiogram. All subjects older than 40 years of age also had an exercise test, without signs of heart disease. In 32 subjects, in whom the recordings were distinct enough throughout the isovolumic contraction and relaxation phases, the dimension changes during these phases were measured. These subjects were 19 to 70 years old. Sixteen were women and 16 were men.
METHODS The echocardiographic examinations were performed with the subjects in the left lateral recumbent position. The equipment used was an Acuson-128 XP (Acuson Co, Mountain View, Calif). A combined 2- and 2.5-MHz transducer was used. Echocardiographic technique and calculations of cardiac dimensions were performed in accordance with the recommendations of the American Society of Echocardiography Committee.26-28 Left ventricular short-axis diameter was measured in the parasternal longaxis view at the level of the chordae tendineae with 3 consecutive expiratory beats. Mitral ring motion was recorded at 4 sites of the mitral ring, situated approximately 90 degrees apart.9,10 Recordings from the septal and lateral parts of the ring were obtained from the apical 4-chamber view and recordings from the posterior and anterior parts
from the apical 2-chamber view. The transducer position giving the least angle error was chosen for each measurement site. The mitral ring motion was measured from the nadir of the curve to the peak point.10 A leading edge technique was used. Three consecutive expiratory beats from each of the 4 sites were used. M-mode measurements of mitral ring motion with this technique has good reproducibility.9,10,29 Because the motion of the epicardial part of the apex is usually less than 1 mm compared with the transducer measured by M-mode recording from apical views,11 the mitral ring motion reflects the overall shortening or lengthening of the left ventricle, measured from the atrioventricular plane to the epicardial part of the apex. Reliable echocardiographic measures of the distance from the mitral ring to the endocardial part of the apex can usually be obtained during diastole but not during systole. The mean thickness of the apical myocardium is only 1.5 mm.8 With the apex as stable point, the adjacent walls thicken and the endocardial parts of the walls move inward during systole, thus obliterating the apical left ventricular cavity and forming a new apparent endocardial apex. This newly formed “endocardial apex” consists largely of trabeculae, a condition that creates a practical problem in identifying the endocardial apex.4,8 In the current study, in which changes in short-axis and long-axis dimensions are compared, it would have been appropriate to use the endocardial part of the apex by analogy with the changes in shortaxis inner diameter of the ventricle, but as mentioned above, reliable measurements cannot be obtained from the endocardial apex during end-systole. The timing of opening and closing of the mitral and aortic valves were identified either from the parasternal M-mode or apical Doppler recordings. Measurements of changes during the isovolumic phases were obtained from printed recordings. Beats with the same R-R duration as the analyzed beat were used. The onset of the isovolumic contraction period coincides with the R wave on the electrocardiogram, usually shortly before the top of the R wave, and the end of the period occurs slightly after the end of the QRS. The beginning of the isovolumic relaxation phase usually coincides with the termi-
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Table 2 Linear correlation between mitral ring motion and age, systolic blood pressure, heart rate, sex, and some echocardiographic measures Tested variable
Age Systolic blood pressure Left ventricular end-systolic diameter Heart rate Left ventricular end-diastolic diameter Systolic short-axis diameter reduction Sex Left ventricular wall thickness
Correlation Level of coefficient significance
2.66 2.53 .40 2.37 .28
P , .001 P , .001 P 5 .010 P 5 .021 NS
2.24 .19 2.16
NS NS NS
NS, Not significant.
nal part of the T wave of the electrocardiogram and the end usually occurs shortly after the end of the T wave (Figure 1). On echocardiographic parasternal M-mode recordings, there are often 2 nadirs on the septal motion. In these cases, the first nadir corresponds to the aortic valve closure, and this is the point where we measured the end-systolic diameter. In some subjects the peak of the posterior wall motion occurs slightly after the nadir of the septal motion. Also in these cases we measured the end-systolic diameter at the first septal nadir, in accordance with previous recommendations.27
Figure 2 Correlation between left ventricular systolic short-axis diameter reduction (SSADR) and age.
Statistics Pearson correlation coefficient was used for analysis of linear correlation between different variables. The 2-tailed t test was used to determine whether correlations were statistically significant. The 5% level was used for significance. Standard deviation of the changes from ages 18 to 70 years was computed from the standard deviation of the regression coefficients. For variables with significant correlation to the left ventricular short-axis contractions, or to the mitral ring motion, stepwise multiple regression analysis was performed.
RESULTS All subjects had normal echocardiographic left atrial and ventricular dimensions.30,31 None had signs of significant aortic or mitral regurgitation in the Doppler recordings. Left ventricular short-axis systolic diameter reduction increased with advancing age (r 5 .39, P 5 .012) and with increasing wall thickness (r 5 .32, P 5 .044) (Tables 1 and 3). Mitral ring motion decreased with advancing age (r 5 2.66, P , .001), increasing systolic blood pressure (r 5 2.53, P , .001), and increasing heart rate (r 5 2.37, P 5 .021) (Table 2).
Figure 3 Correlation between mitral ring motion (MRM) and age.
Stepwise multiple regression analysis, with systolic short-axis diameter reduction and mitral ring motion as dependent variables, showed that age was the most important of the tested variables. R2 was .15 (P 5 .012) for systolic short-axis diameter reduction and .39 (P , .001) for mitral ring motion. No significant additional explicatory power was found when left ventricular wall thickness, systolic blood pressure, heart rate, or sex were added as independent variables. Calculations from the linear regression equations show that from age 18 to 70 years, the systolic short-axis diameter shortening increased by 18%, from 17.2 to 20.4 mm (P 5 .012) (Figure 2 and Table 3) and the mitral ring motion decreased by 20%, from 17.2 to 13.8 mm (P , .001) (Figure 3 and Table 3). Left ventricular end-diastolic short-axis di-
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Table 3 Changes from 18 to age 70 years for some left ventricular dimensions calculated from linear regression equations
Systolic longitudinal shortening Systolic short-axis diameter reduction End-diastolic short-axis diameter End-systolic short-axis diameter Left ventricular wall thickness
Changes in %
Linear correlation to age
Level of significance
23.4 6 0.6 mm
220%
r 5 2.66
P , .001
20.4 mm
23.2 6 1.2 mm
118%
r 5 .39
P 5 .012
52.7 mm
47.8 mm
24.9 6 2.2 mm
29%
r 5 .34
P 5 .031
4.0 mm
35.5 mm
27.5 mm
28.0 6 2.0 mm
223%
r 5 2.54
P , .001
1.0 mm
9.4 mm
11.4 mm
12.0 6 0.5 mm
121%
r 5 .51
P , .001
SEE
Expected value at age 18 years
Expected value at age 70 years
1.2 mm
17.2 mm
13.8 mm
2.3 mm
17.2 mm
4.3 mm
Changes from age 18 to 70 years (6SD)
SEE, Standard error of the estimate (5standard deviation of the residuals).
ameter decreased by 9%, from 52.7 to 47.8 mm (P 5 .031), and the end-systolic diameter by 23%, from 35.5 to 27.5 mm (P , .001). Left ventricular enddiastolic wall thickness, calculated as the mean of septal thickness and posterior wall thickness, increased by 21%, from 9.4 to 11.4 mm (P , .001) (Table 3). During the isovolumic contraction phase, the short-axis diameter increased by 1.2 6 0.9 mm (6SD) (P , .001) and the descent of the mitral ring, toward the apex, was 1.2 6 0.5 mm (6SD) (P , .001). During the isovolumic relaxation phase, the short-axis diameter decreased by 0.6 6 1.3 mm (6SD) (P 5 .010) and the mitral ring ascent, away from the apex, was 0.3 6 0.7 mm (6SD) (P 5 .014). There were no significant correlations between changes in dimensions during the isovolumic phases and age (Table 4). The difference between the lateral part and the septal part of the mitral ring motion was 1.4 6 1.6 mm (SD) (P , .001,) which means that the ring “tilts” during the motion toward the apex during systole. However, there was no significant change in the degree of “tilting” with increasing age.
DISCUSSION Previous studies with radionuclide methods have shown that left ventricular ejection fraction at rest does not change19,21 or increases slightly with age.20 The radionuclide techniques do not allow studies of the mode of contraction, and it is therefore not known whether or not this changes with increasing age. Echocardiography has the advantage that the contraction pattern in both the longitudinal and circumferential planes can be studied in detail and was therefore used in this study, in which we found a
significant reduction in mitral ring motion and a significant increase in short-axis contraction with increasing age. These findings have important practical consequences because both the short-axis dimensions and the mitral ring motion are used for calculating ejection fraction. The most important change with increasing age occurs in the long-axis shortening (r 5 2 .66, SEE 5 1.2, P , .001), whereas there is a weaker correlation between age and short-axis shortening (r 5 .34, P 5 .012), with a considerable scatter about the regression line (SEE 5 2.3). The most common equation for calculation of volumes and ejection fraction from the short axis is that by Teichholz et al,32 which was introduced to allow for changes in left ventricular shape in failing hearts. Applying this formula to our results, we calculate an ejection fraction of 73% at age 70 years, which is higher than that obtained by radionuclide angiography in earlier studies19-21 and significantly higher than that obtained at age 18 years in our study. The ejection fraction at age 18 is 61% in our material, which is similar to that obtained by radionuclide methods (Table 5). This indicates that Teichholz’s formula may overestimate ejection fraction in older subjects by approximately 10% (approximately 7% ejection fraction in normal subjects) but probably gives a fairly correct value in normal young subjects. This means that in elderly with slightly reduced ejection fraction, calculation by Teichholz’s formula might give a value in the lower part of the normal range, and in some subjects a moderate decreased ejection fraction might wrongly be calculated as a mild decrease. Similarly, ejection fraction has been calculated from mitral ring motion with the equation ejection fraction(%) 5 5 3 mitral ring motion (mm). This equation has been derived from studies in which radionuclide angiography or contrast angiography
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Table 4 Changes in left ventricular short-axis and long-axis diameters during isovolumic contraction phase and isovolumic relaxation phase (n 5 32)
Minimum
Maximum
Level of significance of change
11.2 (60.9) mm
0 mm
13.9 mm
P , .001
r 5 2.11 (NS)
21.2 (60.5) mm
22.8 mm
0 mm
P ,.001
r 5 .19 (NS)
20.6 (61.3) mm
24.0 mm
12.8 mm
P 5 .010
r 5 .30 (NS)
10.3 (60.7) mm
21.1 mm
11.6 mm
P 5 .014
r 5 2.06 (NS)
Mean change (6SD)
Changes in short-axis diameter during isovolumic contraction phase Changes in long-axis diameter during isovolumic contraction phase Changes in short-axis diameter during isovolumic relaxation phase Changes in long-axis diameter during isovolumic relaxation phase
Correlation to age
SD, Standard deviation; NS, not significant.
Table 5 Weighted mean values for ejection fraction in healthy subjects from two radionuclide angiographic studies Study included
Pfisterer 1985 Pfisterer 1985 Pfisterer 1985 Bauer 1988 Pfisterer 1985 Bauer 1988 Pfisterer 1985 Bauer 1988
Age group
Mean Ejection fraction (%)
Table 6 Weighted mean values for ejection fraction in healthy subjects from studies by Bauer et al (1988) and Pfisterer et al (1985) and measured mitral ring motion from present study
n Age group
#30 31-40 41-50
61.1 63.6 63.4
58 97 148
51-60
63.9
140
.60
66.4
92
20-30 31-40 41-50 51-60 61-70 71-75
Mean EF (%)
Mean MRM (mm)
Conversion factor
61.1 63.6 63.4 63.9 66.4* 66.4*
16.8 16.1 15.5 14.9 14.3 13.8
3.6 4.0 4.1 4.3 4.6 4.8
In the study of Bauer et al, youngest age group ranged from 18 to 40 years. The study is therefore not included in the two youngest age groups.
EF, Ejection fraction; MRM, mitral ring motion. Conversion factors for different age groups are calculated as mean EF/mean MRM. *Value for whole group .60 years.
was used as the reference method.7,16-18 These studies mainly included middle-aged to elderly adults. Because of the decrease in mitral ring motion with increasing age, the equation shown above will give values of ejection fraction too high in young subjects. In two of the above-mentioned radionuclide angiography studies of ejection fraction, the results were reported for different age groups.19,20 Weighted means from these studies are displayed in Table 5. Calculations with these values for ejection fraction and the regression equation for mitral ring motion and age in this study give much lower conversion factors in young subjects than in elderly (Table 6). According to the different conversion factors, mitral ring motion of 12 mm in a 25-year-old subject means decreased ejection fraction, with a value approximately 43%, whereas in a 73-year-old subject mitral ring motion of 12 mm means a normal ejection fraction, approximately 58%. The change in short- and long-axis dimensions during the isovolumic phases indicates a slight change in ventricular shape during these phases. This
is of importance for which points of measurements should be used. There is agreement for many years that the onset of the QRS is the point at which end-diastolic short-axis diameter should be measured and that the nadir of septal motion is the point at which the ventricular systolic diameter should be measured.27 For mitral ring motion, Ho¨glund et al10 used the distance from the nadir to the peak excursion of contraction. For practical reasons, these points may be the easiest and may give the most reproducible measurements. In our study, which included healthy subjects only, the nadir occurred in the end-diastolic period, before the closure of the mitral valves, in all subjects (n 5 32). However, the highest excursion point in some subjects (7 subjects) occurred in the isovolumic relaxation phase, with an increase in longitudinal shortening up to 1.1 mm, compared with end-systole. In patients with heart disease, however, a much greater change during the isovolumic relaxation period can be seen, resulting in a significant difference between motion at end-systole and maximal downward ring
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motion. When mitral ring motion is used for assessment of left ventricular function, measurements should therefore be made at the time of aortic valve closure, and significant differences between this and the maximal downward motion could be used to indicate increased abnormal shape changes in the isovolumic period. The interpretation of such changes, however, still remains to be investigated. It is not clear from our data why the change in contraction pattern with increasing age occurs. In an unpublished study in patients with increased wall thickness caused by either hypertension or classified as hypertrophic cardiomyopathy, we found decreased shortening in the long axis compared with the short axis, and we hypothesized that this was caused by the increased wall thickness. In this study, however, stepwise multiple regression showed no extra explicatory power of wall thickness in addition to that of age. Left ventricular wall thickness increases and systolic and diastolic inner diameter decreases with increasing age30 (Table 3). Most studies show unchanged heart rate,19,30 decreased stroke volume and cardiac output,33 and unchanged19,21 or slightly increased20 ejection fraction with advancing age. A correlation between decreased left ventricular diastolic diameter and increased short-axis contractions could be expected, as a means to limit the decrease in cardiac output. However, there was no significant correlation between diastolic diameter and short-axis contraction in the current study (Table 1). Neither can other correlations between variables in the study explain the changing pattern of contraction seen with increasing age, except for the correlation to age per se. It may be that there is a connection to the changes that occur on the microscopy-cellular level with advancing age.34,35 In summary, we have shown that the mode of contraction of the heart in normal subjects changes with increasing age; the changes in dimension in the short axis increase, whereas those in the long axis, as reflected by the mitral ring motion, decrease. These findings have important implications for the calculation of ejection fraction from M-mode measures. We gratefully acknowledge Ms Kerstin Ling for her assistance in the preparation of the manuscript and Mr Ingemar Adolfsson for statistical assistance.
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ejection and relaxation of the normal human heart. Am Heart J 1964;67:89-99. Zamfirescu NR, Hartia L, Pop T, Petcu E. Functional peculiarities of the heart in the aged. Physiologie 1982;19:73-9. Guyton AC. Textbook of medical physiology. 7th ed. Philadelphia, Pa: WB Saunders, 1986:155. Wandt B, Bojo¨ L, Wranne B. Influence of body size and age on mitral ring motion. Clin Physiol 1997;17:635-46. Henry WL, De Maria A, Gramiak R, et al. Report of the American Society of Echocardiography Committee on nomenclature and standards in 2-D echocardiography. Circulation 1980;62:212-7. Sahn DJ, De Maria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072-83. Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr 1989;5:358-67. Alam M, Ho¨glund C. Assessment by echocardiogram of left ventricular diastolic function in healthy subjects using the
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Left ventricular ejection fraction is known to be unchanged or slightly increased with advancing age. This echocardiographic study, including 40 healthy subjects 18 to 70 years old, shows that this is a net effect of decreased contractions in the long axis and increased in the short axis. From age 18 to 70 years, the longitudinal shortening decreases by 20% (P < .001) and the short-axis diameter shortening increases by 18% (P 5 .012). Multiple regression analysis showed strong correlation to age for both shortand long-axis contractions and no significant addi-
Left ventricular systole involves both a shortening in the longitudinal axis of the ventricle and a reduction of the inner diameter in the short axis1-4 and a slight rotational movement about the long axis.2 During systole, the epicardial apex of the heart is relatively stationary, whereas the mitral ring moves toward the apex. During diastole it ascends away from the apex, toward the left atrium. This motion has been shown with cineroentgenography of calcified regions of the mitral ring,5,6 with cineangiography,2 with radiopaque markings in the heart after surgery2 and with echocardiography,7-13 with computed tomography,14 and with magnetic resonance imaging.15 A high correlation has been shown between the amplitude of the mitral ring motion and ejection fraction, assessed by radionuclide angiography or by left ventricular angiography in patients with severe congestive heart failure after dilated cardiomyopathy or myocardial infarction,7 in patients with acute myocardial infarction,16 in patients with coronary artery disease,17 and in consecutive patients who had both echocardiogram and radionuclide angiography within 2 days (category of patients not mentioned).18 Previous studies with radionuclide angiography have shown that left ventricular ejection fraction at rest in adults is unchanged From the Department of Clinical Physiology, Central Hospital, and the Department of Clinical Physiology, Linko¨ping University Hospital. Supported in part by Swedish Medical Research Council grant 9481 and the Swedish Heart Lung Foundation. Reprint requests: Birger Wandt, MD, Department of Clinical Physiology, Central Hospital, S-651 85 Karlstad, Sweden. Copyright © 1998 by the American Society of Echocardiography. 0894-7317/98 $5.00 1 0 27/1/91281
tional explicatory power when the variables systolic blood pressure, left ventricular wall thickness, heart rate, or sex were included. There was no significant correlation between diameter changes during the isovolumic phases and age. The findings have practical implications when calculating ejection fraction from M-mode measurements. Teichholz’s formula will overestimate ejection fraction in elderly subjects, and calculation of ejection fraction from mitral ring motion will overestimate it in young subjects. (J Am Soc Echocardiogr 1998;11:857-63.)
or slightly increased with advancing age.19-21 This does not exclude the possibility of changes in circumferential or longitudinal shortening with age. One aim of the this study was to investigate this possibility. Previous studies have shown that the length of the isovolumic relaxation period increases with increasing age and that the isovolumic contraction phase tends to lengthen slightly with advancing age.22,23 It is also well known that there is a change in left ventricular shape during the isovolumic contraction period, with an apex-to-base shortening and a circumferential elongation.11,24 It is not clear, however, whether there is also a change in ventricular shape during the isovolumic relaxation period. Another aim of this study, therefore, was to investigate whether changes in ventricular shape during the isovolumic relaxation phase can be established by parasternal and apical M-mode recordings and to investigate if the degree of changes in the shape during the isovolumic periods changes with age. Previous studies have shown that the lateral part of the mitral ring moves a longer distance than the septal part.9,25 This means that the ring “tilts” during the motion toward the apex. It is not previously known whether the degree of “tilting” changes with age. An additional aim of the study was therefore to investigate whether the “tilting” motion of the mitral ring increases with advancing age. Study Population Forty subjects, mainly hospital employees and relatives 18 to 70 years old, were studied; there were 17 857
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Table 1 Linear correlation between left ventricular systolic short-axis diameter reduction and age, systolic blood pressure, sex, heart rate, and some echocardiographic measures Tested variable
Age Left ventricular wall thickness Left ventricular end-diastolic diameter Mitral ring motion Systolic blood pressure Left ventricular end-systolic diameter Sex Heart rate
Correlation Level of coefficient significance
.39 .32 .29 2.24 .22 2.17 .16 .07
P 5 .012 P 5 .044 NS NS NS NS NS NS
NS, Not significant.
Figure 1 Parasternal M-mode recording of left ventricle and apical recording of mitral ring motion in 35-year-old healthy woman.
women and 23 men. They had no history of cardiac disease, normal findings on physical examination, and a normal resting electrocardiogram. All subjects older than 40 years of age also had an exercise test, without signs of heart disease. In 32 subjects, in whom the recordings were distinct enough throughout the isovolumic contraction and relaxation phases, the dimension changes during these phases were measured. These subjects were 19 to 70 years old. Sixteen were women and 16 were men.
METHODS The echocardiographic examinations were performed with the subjects in the left lateral recumbent position. The equipment used was an Acuson-128 XP (Acuson Co, Mountain View, Calif). A combined 2- and 2.5-MHz transducer was used. Echocardiographic technique and calculations of cardiac dimensions were performed in accordance with the recommendations of the American Society of Echocardiography Committee.26-28 Left ventricular short-axis diameter was measured in the parasternal longaxis view at the level of the chordae tendineae with 3 consecutive expiratory beats. Mitral ring motion was recorded at 4 sites of the mitral ring, situated approximately 90 degrees apart.9,10 Recordings from the septal and lateral parts of the ring were obtained from the apical 4-chamber view and recordings from the posterior and anterior parts
from the apical 2-chamber view. The transducer position giving the least angle error was chosen for each measurement site. The mitral ring motion was measured from the nadir of the curve to the peak point.10 A leading edge technique was used. Three consecutive expiratory beats from each of the 4 sites were used. M-mode measurements of mitral ring motion with this technique has good reproducibility.9,10,29 Because the motion of the epicardial part of the apex is usually less than 1 mm compared with the transducer measured by M-mode recording from apical views,11 the mitral ring motion reflects the overall shortening or lengthening of the left ventricle, measured from the atrioventricular plane to the epicardial part of the apex. Reliable echocardiographic measures of the distance from the mitral ring to the endocardial part of the apex can usually be obtained during diastole but not during systole. The mean thickness of the apical myocardium is only 1.5 mm.8 With the apex as stable point, the adjacent walls thicken and the endocardial parts of the walls move inward during systole, thus obliterating the apical left ventricular cavity and forming a new apparent endocardial apex. This newly formed “endocardial apex” consists largely of trabeculae, a condition that creates a practical problem in identifying the endocardial apex.4,8 In the current study, in which changes in short-axis and long-axis dimensions are compared, it would have been appropriate to use the endocardial part of the apex by analogy with the changes in shortaxis inner diameter of the ventricle, but as mentioned above, reliable measurements cannot be obtained from the endocardial apex during end-systole. The timing of opening and closing of the mitral and aortic valves were identified either from the parasternal M-mode or apical Doppler recordings. Measurements of changes during the isovolumic phases were obtained from printed recordings. Beats with the same R-R duration as the analyzed beat were used. The onset of the isovolumic contraction period coincides with the R wave on the electrocardiogram, usually shortly before the top of the R wave, and the end of the period occurs slightly after the end of the QRS. The beginning of the isovolumic relaxation phase usually coincides with the termi-
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Wandt et al 859
Table 2 Linear correlation between mitral ring motion and age, systolic blood pressure, heart rate, sex, and some echocardiographic measures Tested variable
Age Systolic blood pressure Left ventricular end-systolic diameter Heart rate Left ventricular end-diastolic diameter Systolic short-axis diameter reduction Sex Left ventricular wall thickness
Correlation Level of coefficient significance
2.66 2.53 .40 2.37 .28
P , .001 P , .001 P 5 .010 P 5 .021 NS
2.24 .19 2.16
NS NS NS
NS, Not significant.
nal part of the T wave of the electrocardiogram and the end usually occurs shortly after the end of the T wave (Figure 1). On echocardiographic parasternal M-mode recordings, there are often 2 nadirs on the septal motion. In these cases, the first nadir corresponds to the aortic valve closure, and this is the point where we measured the end-systolic diameter. In some subjects the peak of the posterior wall motion occurs slightly after the nadir of the septal motion. Also in these cases we measured the end-systolic diameter at the first septal nadir, in accordance with previous recommendations.27
Figure 2 Correlation between left ventricular systolic short-axis diameter reduction (SSADR) and age.
Statistics Pearson correlation coefficient was used for analysis of linear correlation between different variables. The 2-tailed t test was used to determine whether correlations were statistically significant. The 5% level was used for significance. Standard deviation of the changes from ages 18 to 70 years was computed from the standard deviation of the regression coefficients. For variables with significant correlation to the left ventricular short-axis contractions, or to the mitral ring motion, stepwise multiple regression analysis was performed.
RESULTS All subjects had normal echocardiographic left atrial and ventricular dimensions.30,31 None had signs of significant aortic or mitral regurgitation in the Doppler recordings. Left ventricular short-axis systolic diameter reduction increased with advancing age (r 5 .39, P 5 .012) and with increasing wall thickness (r 5 .32, P 5 .044) (Tables 1 and 3). Mitral ring motion decreased with advancing age (r 5 2.66, P , .001), increasing systolic blood pressure (r 5 2.53, P , .001), and increasing heart rate (r 5 2.37, P 5 .021) (Table 2).
Figure 3 Correlation between mitral ring motion (MRM) and age.
Stepwise multiple regression analysis, with systolic short-axis diameter reduction and mitral ring motion as dependent variables, showed that age was the most important of the tested variables. R2 was .15 (P 5 .012) for systolic short-axis diameter reduction and .39 (P , .001) for mitral ring motion. No significant additional explicatory power was found when left ventricular wall thickness, systolic blood pressure, heart rate, or sex were added as independent variables. Calculations from the linear regression equations show that from age 18 to 70 years, the systolic short-axis diameter shortening increased by 18%, from 17.2 to 20.4 mm (P 5 .012) (Figure 2 and Table 3) and the mitral ring motion decreased by 20%, from 17.2 to 13.8 mm (P , .001) (Figure 3 and Table 3). Left ventricular end-diastolic short-axis di-
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860 Wandt et al
Table 3 Changes from 18 to age 70 years for some left ventricular dimensions calculated from linear regression equations
Systolic longitudinal shortening Systolic short-axis diameter reduction End-diastolic short-axis diameter End-systolic short-axis diameter Left ventricular wall thickness
Changes in %
Linear correlation to age
Level of significance
23.4 6 0.6 mm
220%
r 5 2.66
P , .001
20.4 mm
23.2 6 1.2 mm
118%
r 5 .39
P 5 .012
52.7 mm
47.8 mm
24.9 6 2.2 mm
29%
r 5 .34
P 5 .031
4.0 mm
35.5 mm
27.5 mm
28.0 6 2.0 mm
223%
r 5 2.54
P , .001
1.0 mm
9.4 mm
11.4 mm
12.0 6 0.5 mm
121%
r 5 .51
P , .001
SEE
Expected value at age 18 years
Expected value at age 70 years
1.2 mm
17.2 mm
13.8 mm
2.3 mm
17.2 mm
4.3 mm
Changes from age 18 to 70 years (6SD)
SEE, Standard error of the estimate (5standard deviation of the residuals).
ameter decreased by 9%, from 52.7 to 47.8 mm (P 5 .031), and the end-systolic diameter by 23%, from 35.5 to 27.5 mm (P , .001). Left ventricular enddiastolic wall thickness, calculated as the mean of septal thickness and posterior wall thickness, increased by 21%, from 9.4 to 11.4 mm (P , .001) (Table 3). During the isovolumic contraction phase, the short-axis diameter increased by 1.2 6 0.9 mm (6SD) (P , .001) and the descent of the mitral ring, toward the apex, was 1.2 6 0.5 mm (6SD) (P , .001). During the isovolumic relaxation phase, the short-axis diameter decreased by 0.6 6 1.3 mm (6SD) (P 5 .010) and the mitral ring ascent, away from the apex, was 0.3 6 0.7 mm (6SD) (P 5 .014). There were no significant correlations between changes in dimensions during the isovolumic phases and age (Table 4). The difference between the lateral part and the septal part of the mitral ring motion was 1.4 6 1.6 mm (SD) (P , .001,) which means that the ring “tilts” during the motion toward the apex during systole. However, there was no significant change in the degree of “tilting” with increasing age.
DISCUSSION Previous studies with radionuclide methods have shown that left ventricular ejection fraction at rest does not change19,21 or increases slightly with age.20 The radionuclide techniques do not allow studies of the mode of contraction, and it is therefore not known whether or not this changes with increasing age. Echocardiography has the advantage that the contraction pattern in both the longitudinal and circumferential planes can be studied in detail and was therefore used in this study, in which we found a
significant reduction in mitral ring motion and a significant increase in short-axis contraction with increasing age. These findings have important practical consequences because both the short-axis dimensions and the mitral ring motion are used for calculating ejection fraction. The most important change with increasing age occurs in the long-axis shortening (r 5 2 .66, SEE 5 1.2, P , .001), whereas there is a weaker correlation between age and short-axis shortening (r 5 .34, P 5 .012), with a considerable scatter about the regression line (SEE 5 2.3). The most common equation for calculation of volumes and ejection fraction from the short axis is that by Teichholz et al,32 which was introduced to allow for changes in left ventricular shape in failing hearts. Applying this formula to our results, we calculate an ejection fraction of 73% at age 70 years, which is higher than that obtained by radionuclide angiography in earlier studies19-21 and significantly higher than that obtained at age 18 years in our study. The ejection fraction at age 18 is 61% in our material, which is similar to that obtained by radionuclide methods (Table 5). This indicates that Teichholz’s formula may overestimate ejection fraction in older subjects by approximately 10% (approximately 7% ejection fraction in normal subjects) but probably gives a fairly correct value in normal young subjects. This means that in elderly with slightly reduced ejection fraction, calculation by Teichholz’s formula might give a value in the lower part of the normal range, and in some subjects a moderate decreased ejection fraction might wrongly be calculated as a mild decrease. Similarly, ejection fraction has been calculated from mitral ring motion with the equation ejection fraction(%) 5 5 3 mitral ring motion (mm). This equation has been derived from studies in which radionuclide angiography or contrast angiography
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Table 4 Changes in left ventricular short-axis and long-axis diameters during isovolumic contraction phase and isovolumic relaxation phase (n 5 32)
Minimum
Maximum
Level of significance of change
11.2 (60.9) mm
0 mm
13.9 mm
P , .001
r 5 2.11 (NS)
21.2 (60.5) mm
22.8 mm
0 mm
P ,.001
r 5 .19 (NS)
20.6 (61.3) mm
24.0 mm
12.8 mm
P 5 .010
r 5 .30 (NS)
10.3 (60.7) mm
21.1 mm
11.6 mm
P 5 .014
r 5 2.06 (NS)
Mean change (6SD)
Changes in short-axis diameter during isovolumic contraction phase Changes in long-axis diameter during isovolumic contraction phase Changes in short-axis diameter during isovolumic relaxation phase Changes in long-axis diameter during isovolumic relaxation phase
Correlation to age
SD, Standard deviation; NS, not significant.
Table 5 Weighted mean values for ejection fraction in healthy subjects from two radionuclide angiographic studies Study included
Pfisterer 1985 Pfisterer 1985 Pfisterer 1985 Bauer 1988 Pfisterer 1985 Bauer 1988 Pfisterer 1985 Bauer 1988
Age group
Mean Ejection fraction (%)
Table 6 Weighted mean values for ejection fraction in healthy subjects from studies by Bauer et al (1988) and Pfisterer et al (1985) and measured mitral ring motion from present study
n Age group
#30 31-40 41-50
61.1 63.6 63.4
58 97 148
51-60
63.9
140
.60
66.4
92
20-30 31-40 41-50 51-60 61-70 71-75
Mean EF (%)
Mean MRM (mm)
Conversion factor
61.1 63.6 63.4 63.9 66.4* 66.4*
16.8 16.1 15.5 14.9 14.3 13.8
3.6 4.0 4.1 4.3 4.6 4.8
In the study of Bauer et al, youngest age group ranged from 18 to 40 years. The study is therefore not included in the two youngest age groups.
EF, Ejection fraction; MRM, mitral ring motion. Conversion factors for different age groups are calculated as mean EF/mean MRM. *Value for whole group .60 years.
was used as the reference method.7,16-18 These studies mainly included middle-aged to elderly adults. Because of the decrease in mitral ring motion with increasing age, the equation shown above will give values of ejection fraction too high in young subjects. In two of the above-mentioned radionuclide angiography studies of ejection fraction, the results were reported for different age groups.19,20 Weighted means from these studies are displayed in Table 5. Calculations with these values for ejection fraction and the regression equation for mitral ring motion and age in this study give much lower conversion factors in young subjects than in elderly (Table 6). According to the different conversion factors, mitral ring motion of 12 mm in a 25-year-old subject means decreased ejection fraction, with a value approximately 43%, whereas in a 73-year-old subject mitral ring motion of 12 mm means a normal ejection fraction, approximately 58%. The change in short- and long-axis dimensions during the isovolumic phases indicates a slight change in ventricular shape during these phases. This
is of importance for which points of measurements should be used. There is agreement for many years that the onset of the QRS is the point at which end-diastolic short-axis diameter should be measured and that the nadir of septal motion is the point at which the ventricular systolic diameter should be measured.27 For mitral ring motion, Ho¨glund et al10 used the distance from the nadir to the peak excursion of contraction. For practical reasons, these points may be the easiest and may give the most reproducible measurements. In our study, which included healthy subjects only, the nadir occurred in the end-diastolic period, before the closure of the mitral valves, in all subjects (n 5 32). However, the highest excursion point in some subjects (7 subjects) occurred in the isovolumic relaxation phase, with an increase in longitudinal shortening up to 1.1 mm, compared with end-systole. In patients with heart disease, however, a much greater change during the isovolumic relaxation period can be seen, resulting in a significant difference between motion at end-systole and maximal downward ring
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862 Wandt et al
motion. When mitral ring motion is used for assessment of left ventricular function, measurements should therefore be made at the time of aortic valve closure, and significant differences between this and the maximal downward motion could be used to indicate increased abnormal shape changes in the isovolumic period. The interpretation of such changes, however, still remains to be investigated. It is not clear from our data why the change in contraction pattern with increasing age occurs. In an unpublished study in patients with increased wall thickness caused by either hypertension or classified as hypertrophic cardiomyopathy, we found decreased shortening in the long axis compared with the short axis, and we hypothesized that this was caused by the increased wall thickness. In this study, however, stepwise multiple regression showed no extra explicatory power of wall thickness in addition to that of age. Left ventricular wall thickness increases and systolic and diastolic inner diameter decreases with increasing age30 (Table 3). Most studies show unchanged heart rate,19,30 decreased stroke volume and cardiac output,33 and unchanged19,21 or slightly increased20 ejection fraction with advancing age. A correlation between decreased left ventricular diastolic diameter and increased short-axis contractions could be expected, as a means to limit the decrease in cardiac output. However, there was no significant correlation between diastolic diameter and short-axis contraction in the current study (Table 1). Neither can other correlations between variables in the study explain the changing pattern of contraction seen with increasing age, except for the correlation to age per se. It may be that there is a connection to the changes that occur on the microscopy-cellular level with advancing age.34,35 In summary, we have shown that the mode of contraction of the heart in normal subjects changes with increasing age; the changes in dimension in the short axis increase, whereas those in the long axis, as reflected by the mitral ring motion, decrease. These findings have important implications for the calculation of ejection fraction from M-mode measures. We gratefully acknowledge Ms Kerstin Ling for her assistance in the preparation of the manuscript and Mr Ingemar Adolfsson for statistical assistance.
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