Copyright © 2004, The European Society of Cardiology
Age-related intramyocardial patterns in healthy subjects evaluated with Doppler tissue imaging
aLaboratorio de Ecocardiografía, Department of Cardiology, Hospital Gregorio Marañón, C/Doctor Esquerdo, 46, 28007 Madrid, Spain
bETSIT-Universidad Politécnica de Madrid, Spain
cPhysics Department, Universidad Nacional de Educación a Distancia, Spain
dExperimental Medicine, Hospital Gregorio Marañón, Spain
Received 29 January 2004; received in revised form 24 May 2004; accepted after revision 9 August 2004.
* Presented in part at the Scientific Sessions of the American Heart Association, November 2002, Chicago, Illinois.
* Corresponding author. Tel.: +34 91 586 82 83; fax: +34 91 586 67 27. E-mail addresses: eperezdavid{at}arrakis.es (E. Perez-David), magfeco{at}primus.es (M.A. Garcia-Fernandez), mledesma{at}die.upm.es (M.J. Ledesma), nmalpica{at}die.upm.es (N. Malpica), tlf{at}eresmas.com (T.L. Fernandez), desco{at}mce.hggm.es (M. Desco).
1 Tel.: +34 91 586 82 83; fax: +34 91 586 67 27.
2 Tel.: +34 91 586 66 78.
| Abstract |
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Background The aim of this study is to analyse spatial distribution of myocardial velocities (MV) and myocardial velocity gradient (MVG) with color M-mode Doppler tissue imaging (DTI) and to analyse the influence of age in such parameters.
Methods and results A prospective study including 66 healthy volunteers was carried out with color M-mode DTI. Postprocessing of images was performed using proprietary software allowing the division of the myocardial wall into subendocardium, mesocardium and subepicardium. MV corresponding to the three layers and MVG time curves were obtained and systolic, early diastolic and late diastolic peak values were identified. MV were highest in subendocardium in systole, protodiastole and telediastole compared to external layers. Protodiastolic peak MV decreased in all layers with age, but with a higher impact in the subendocardium (r=0.72, b=0.136 (IC 95% 0.107–0.164), p=0.0005). Older age resulted in larger telediastolic peak MV, without significant differences among layers. Linear correlation between protodiastolic peak mitral flow and peak protodiastolic velocity was higher in endocardium than in other layers (r=0.79, p=0.0005).
Conclusions Color M-mode DTI multilayer analysis showed that endocardium is more susceptible to age-related changes involving diastolic function. This dependency on age should be considered when assessing MV in other clinical settings.
Keywords: Doppler tissue imaging (DTI); Echocardiography; Aging
| Introduction |
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Normal changes in the aging heart have been extensively studied with different diagnostic techniques.1 Doppler tissue imaging allows for quantification of regional function, thus providing a useful tool to objectively analyse the impact of age in myocardial performance. Several papers have addressed this issue, initially by means of color M-mode pulsed Doppler tissue imaging (DTI) and more recently with Doppler-derived velocity, strain and strain rate.2–5 Most of these works have been focused in the evaluation of changes in longitudinal function with age, though some data are also available concerning the effects of aging in radial function.
However, not only transmural regional function is known to be influenced by age. It has been suggested that separate evaluation of the different myocardial layers can be more accurate to detect age-related myocardial dysfunction.6,7
Color M-mode DTI is an accurate method to assess the non-uniformity of transmural myocardial velocities and could be used for the purpose of evaluating the impact of age in the different myocardial layers.8 Transmural MV and myocardial velocity gradients (MVG) have been analysed in healthy hearts and in other clinical conditions.9–11 However, functional analysis of velocities corresponding to different myocardial layers using color M-mode DTI has been neglected in spite of its excellent spatial and temporal resolution.
The purpose of this study is to evaluate age-related changes in MV with color M-mode DTI in three different layers (subendocardium, mesocardium and subepicardium). In order to describe physiologic age-related intramyocardial functional patterns a healthy population with a broad age spectrum was used.
| Methods |
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Study population
Seventy-five healthy volunteers with no history of current or remote cardiac disease or any current medical illness were recruited for this study. Patients with hypertension and diabetes were excluded. Three patients were excluded for pathologic findings in the standard echocardiographic study and six patients because of poor image quality. Informed consent was obtained from all subjects prior to entry into the study. The study group consisted of 66 patients (38 females and 28 males). Mean age was 42±20 years old (range: 18–94). There were 9 participants between 18 and 25 years old (13.6%), 11 between 26 and 35 years old (16.7%), 12 between 36 and 45 years old (18.2%), 10 between 46 and 55 years old (15.2%), 11 between 56 and 65 years old (15.2%), and 13 above 65 years (19.7%). Their resting heart rates varied between 47bpm and 84bpm (mean 67±10bpm). Their systolic blood pressure varied from 80 to 120mmHg (mean: 110±10mmHg) and their diastolic blood pressure varied from 60 to 80mmHg (mean: 70±10mmHg).
Echocardiographic study
A standard transthoracic echocardiographic examination was performed with an Acuson-Siemens Sequoia System ultrasound scanner equipped with a phased-array 3.5MHz transducer and DTI capabilities. M-mode measurements of left ventricle diameters, septum and posterior wall thickness were taken at the level of the mitral valve leaflets tips in the parasternal long-axis (PLAX) view, in telediastole and telesystole. Pulsed Doppler E and A transmitral velocities were measured on the apical view with the sample volume placed at the mitral valve leaflets tips. Table 1 shows standard echocardiographic data from the study population according to age.
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Color Doppler M-mode myocardial imaging
Simultaneous separate recordings of M-mode grey-scale and color DTI were obtained from the basal posterior segment in a PLAX view, ensuring a perpendicular incidence of scanline.
The region of interest corresponding to myocardial posterior wall was magnified. The DTI color scale velocity map was adjusted to a velocity of 23cms–1 to minimize aliasing. When a good quality record was shown, a sequence of
2 consecutive beats was acquired at end-expiration, digitally stored and transferred to a workstation for image analysis. This was accomplished using proprietary software developed in our institution, which has been previously validated.12,13
Quantitative velocity information was obtained from the color calibration bar displayed at the side of the Doppler myocardial image. A selective median filtering algorithm was used to correct black spots, which are a source of error in the calculation of DTI velocities.12,13 At least two cycles were averaged using the onset of the ECG R wave in order to improve the signal-to-noise ratio.
Spline curves were adjusted to endocardial and epicardial boundaries and the wall was automatically divided into three layers of equal thickness, corresponding to subendocardium, mesocardium and subepicardium. This segmentation was performed in greyscale imaging and automatically exported to color M-mode DTI.
The mean MV in these three different layers was calculated along the cardiac cycle. The mean layer velocities were defined as the average value of the MV measured along each M-mode scanline throughout the thickness of the layer. Peak mean velocity was defined as the maximum value of the mean velocity during a particular cardiac phase. MVG was calculated as the unitary spatial rate of change of velocity across the myocardium.14 MV were considered positive when myocardium was moving toward the centre of the left ventricle.
The beginning of systole was set at the beginning of QRS in the electrocardiographic tracing; the end of systole was identified as the moment of cardiac cycle where MVG diminished to zero at the end of the red band in the color M-mode image, as previously defined by other authors.15 Peak MV and MVG in systole, early diastole and late diastole were identified.
Two examples of MV and MVG patterns corresponding to young and elderly patients can be seen in Fig. 1.
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Intraobserver and interobserver variability
A cardiologist, experienced in the performance of DTI studies, obtained standard echocardiographic examinations and color M-mode image acquisition. The same cardiologist carried out postprocessing of images and assessed intraobserver variability. Six months after this first examination the same cardiologist carried out a secondary analysis from a random sample of 15 cases belonging to the whole volunteer group.
A second cardiologist experienced in DTI and blind to the previous results, assessed interobserver variability by performing an analysis of another random sample of 15 cases from the whole series.
Statistical analysis
All statistical procedures were performed with a standard statistical package (SPSS 9.0). The data were expressed as mean value and standard deviation (mean±SD). Paired Student's t-test was used to compare peak velocities.
Pearson's correlation coefficient was determined to assess the possible association between DTI measurements (peak velocity in the three myocardial layers and peak MVG) and age. Linear regression analysis was used to obtain regression equations describing the slope of such relationship. 95% confidence intervals of the regression equations' slopes were calculated and differences between slopes were considered significant following such confidence intervals. Correlation between DTI measurements and standard echocardiographic measurements of left ventricular function was also tested with Pearson's coefficient and the slope of the relationship obtained by linear regression analysis. p<0.05 was considered significant.
Interobserver and intraobserver variabilities were assessed using the Bland–Altman technique.16
| Results |
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Doppler tissue velocities across myocardial layers
MV were highest in subendocardium throughout the cardiac cycle compared to mesocardium and subepicardium, as shown in Fig. 2. Differences among layers were most prominent in early diastole, but significant differences among layers also existed in late diastole and systole.
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Age-dependency in Doppler tissue myocardial velocities
The relationship between results from DTI measurements obtained in diastole and age is displayed in Figs. 3 and 4
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Conversely, peak telediastolic velocity and MVG significantly increased in the three layers with age. In this case, influence of age had a similar impact in the three layers. Subendocardial late diastolic velocity showed a regression slope of 0.067cms–1year–1 that was not significantly different from slopes corresponding to external layers.
No correlation with age was demonstrated between peak systolic velocities nor peak systolic MVG corresponding to the different myocardial layers.
Age-related changes in standard echocardiographic parameters
Transmitral E-wave velocities decreased with age (regression slope of –0.0071ms–1year–1, r=0.69, p=0.0005), whereas A-wave velocities rose with age (regression slope of 0.0067ms–1year–1, r=0.73, p=0.0005). Conversely, no age-dependency was observed regarding echocardiographic parameters of systolic left ventricular function (see Fig. 5).
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Relationship between transmitral Doppler velocities and myocardial velocities
Peak early diastolic MV in all three myocardial layers were associated with protodiastolic mitral inflow, but linear correlation was highest between peak subendocardial protodiastolic velocity and E wave (r=0.79, p=0.0005). Excellent linear correlation was also observed between peak protodiastolic MVG and protodiastolic mitral inflow (r=0.81, p=0.0005). In the same way, telediastolic mitral inflow correlated significantly with late diastolic peak MV in the three layers and peak MVG.
Intraobserver and interobserver variability
There was a low variability between measurements obtained by the same observer, both in MV and MVG. The following values correspond to the mean difference and standard deviation between measurements in MV: in systolic MV, 0.08±0.02cms–1 with r: 0.94 (p<0.0005), in early diastolic MV, 0.37±0.16cms–1 with r: 0.96 (p<0.0005) and in late diastolic MV, 0.31±0.20cms–1 r: 0.96 (p<0.0005). The following values correspond to the mean difference and standard deviation between measurements in MVG: in systolic MVG, 0.19±0.05cms–1 with r: 0.87 (p<0.0005), in early diastolic MVG, 0.45±0.24cms–1 with r: 0.74 (p=0.005) and in late diastolic MVG, 0.30±0.22cms–1 with r: 0.79 (p<0.0005).
The two measurements obtained by the two different blind observers also showed low variability. The following values correspond to the mean difference and standard deviation between measurements from different observers: systolic MV, 0.13±0.15cms–1 with r=0.86 (p=0.0005), early diastolic MV, 0.45±0.17cms–1 with r=0.85 (p<0.0005) and late diastolic MV 0.32±0.19cms–1 with r=0.84 (p<0.0005). The corresponding data from MVG are the following: in systolic MVG, 0.21±0.05cms–1 with r: 0.84 (p<0.0005), in early diastolic MVG, 0.48±0.27cms–1 with r: 0.72 (p=0.004) and in late diastolic MVG, 0.34±0.24cms–1 with r: 0.75 (p=0.005).
| Discussion |
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Our method of analysis of myocardial velocities in color-M mode DTI images enabled us to assess radial function in the different myocardial layers. Consistent differences in MV were observed across the myocardial wall in all groups of age, with higher velocities in the subendocardium both in systole and in diastole. Besides, our results suggest that impact of age in radial function is particularly relevant in diastole. In protodiastole, impairment of MV was more prominent in the subendocardial layer, whereas in telediastole MV increased progressively with age in all myocardial layers.
Possible mechanisms for the different velocities in the myocardial layers
The distribution of MV across the myocardium was asymmetrical, showing higher velocities in the subendocardium than in the subepicardium. This behaviour was observed in peak systolic MV, peak protodiastolic MV and peak telediastolic MV. These data were confirmed by MVG curves across a broad age range.
Irregularity of myocardial wall thickening of left ventricle during systole has been widely described.8,17 Sabbah et al.18 reported that the maximal rate of systolic thickening of the total ventricular wall was higher than the maximal rate of systolic thickening of the epicardial portion. Several explanations for this phenomenon have been suggested. Models of left ventricular wall mechanics have demonstrated that the orientation of cardiac fibers, which is heterogeneous in the normal heart, determines the distribution of fiber strain during ejection.19 Greater dimensional changes in subendocardium during systole are also consistent with predictions based on geometric constraints in a model of concentric cylinders, due to incompressibility of the myocardium.20
In early diastole, the maximal rate of thinning of the total wall during diastole was significantly greater than the maximal rate of thinning of the epicardial portion in experimental models.18 A previous report from Palka et al.11 evaluating DTI in healthy subjects also concluded that subendocardium moved faster than subepicardium during rapid ventricular filling. It has been suggested that protodiastolic MV reflect the process of active myocardial relaxation.21 Early diastolic left ventricular filling has long been known as an active, energy-consuming phenomenon.22 The non-uniform distribution of velocities in this period could be explained by a more active role played by subendocardial and mesocardial layers in myocardial relaxation.
Possible mechanisms of age-dependency on diastolic myocardial velocities
In all three myocardial layers protodiastolic MV decreased significantly with age. However, the impact of age was higher in the peak velocity of the subendocardium than in external myocardial layers. When assessed with protodiastolic MVG a relative change in balance across the three layers was observed; in addition, an absolute change in velocities also existed.
The relationship between age and relaxation of the normal myocardium is well known. Studies in isolated muscle preparations demonstrated prolonged relaxation in aged rats.23 A progressive prolongation of myocardial relaxation also occurs in the human heart with normal aging.24 The decrease in protodiastolic MV with age probably reflects this phenomenon. This finding has also been reported in other studies: Yamada et al. found a good inverse correlation between pulsed E wave and age both in the long axis and the short axis of the left ventricle.2 The impact of age on LV diastolic long-axis performance has also been studied by Henein et al., using pulsed DTI, and, more recently, by Sun et al. with 2D-DTI. In both papers a highly significant effect of age on LV diastolic long-axis performance is reported, and an opposite behaviour of protodiastolic and telediastolic MV occurs reflecting age-related diastolic dysfunction.4,25
In our series, the impact of age was higher in protodiastolic subendocardial velocities than in external layers. Experimental studies by Anversa et al. have demonstrated that progressive myocardial cell loss in senescent animals and replacement fibrosis take place mainly in the subendocardium of the left ventricle.26 A wider extent of damage in subendocardium compared to external layers could explain the greater loss of its relaxation capability.
Subendocardium is a critical area in the left ventricular myocardium. Its larger oxygen consumption makes it more sensitive to ischemia or increased afterload.27 Indeed, normal aging is related to an increase in afterload. A progressive increase in aortic diameter with age has been reported, which in turn tends to compensate for the increased aortic stiffness associated with age, at the expense of increasing impedance.28 Age-associated changes in stiffness of the peripheral vascular bed may also produce an increase in total vascular resistance and therefore in impedance.1
Telediastolic peak velocities increased progressively with age in all myocardial layers. This phenomenon reflects the increasing importance of atrial emptying observed in normal aging to reach the end-diastolic volume necessary to maintain the cardiac output. Many studies have underlined this age-related change in balance between protodiastolic and telediastolic velocity profiles both in transmitral flow and in MV.2,4,25,29
Impact of age in intramyocardial function was similar among the different myocardial layers in telediastole. The different behaviour of age-related changes in late diastole compared to early diastole is related to the physiologic differences existing between these two periods. Telediastolic MV seem to be more related to atrial contraction than to active phenomena located in the left ventricle.25 For this reason, specific changes in the subendocardium, which could be critical in protodiastole, are probably not relevant in late diastole.
Relationship of DTI parameters with standard echocardiographic parameters
Good correlation was shown between DTI measurements and transmitral blood flow parameters. Among the different layers, the strongest correlation was found between peak endocardial protodiastolic velocity and E transmitral wave. These results underline the active role played by subendocardium in the early diastolic filling. During late diastole, good correlation was observed between DTI parameters and A transmitral wave. Correlation between A wave and peak subendocardial velocities was higher than with other layers though the differences were not as important as in the early diastole. This suggests a more homogeneous distribution of velocities throughout the myocardial wall.
These results are in agreement with other reports in healthy patients in which the relationship between DTI parameters and transmitral flow velocities was evaluated.11,25 When preload is normal, a high correlation between MV and transmitral flow indices is expected.11 This is not the case when an elevation of filling pressure is present; as happens in many cardiomyopathies as DTI parameters such as peak negative MVG are less affected by preload alterations than transmitral flow velocity indices.22
Additional information provided by multilayer myocardial velocities compared to standard DTI studies
Early diastolic MV declined significantly with age in the three layers, but to a greater extent in subendocardium. This phenomenon produces a progressive age-related variation of intramyocardial function so that different intramyocardial functional patterns can be found in healthy patients. Our results based on DTI multilayer analysis show that not only is there a change in MVG but that absolute values of MV are also decreased in the three layers. In protodiastole, peak endocardial velocity was approximately 49% lower in an 80-year-old volunteer than in a 30-year-old.
Palka et al.11 did not find a good correlation between transmural peak protodiastolic velocities and age in a group of healthy volunteers, whereas excellent correlation was found with protodiastolic MVG. The authors explained these results by the fact that peak velocities were less accurate than MVG in studying regional diastolic function because they are more affected by overall heart motion. In addition to this we hypothesize that the heterogeneity of roles played by the different layers in the early diastole may be heavily related to this finding.
| Limitations |
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Color M-mode images can only be correctly acquired when the ultrasound beam is perpendicular to the myocardium. This condition is best fulfilled in the basal segment of the posterior wall but most cardiac segments cannot be analysed correctly with this technique. A recent report from Henein et al.25 concluded that age-related changes in velocities were most marked at the basal level. It can therefore be assumed that the basal segment of the posterior wall is a suitable area to study age-related changes in MV.
This kind of analysis allows us to investigate radial, but not longitudinal function. However, significant differences between long- and short-axis motion features have been described.2,30 Further studies focused on the comparison of the role of the different layers in longitudinal and radial function are warranted.
Coronary lesions are frequently found in elderly people31 and asymptomatic ischemic heart disease could modify some DTI parameters. In our study, patients with pathologic findings in standard echocardiographic studies and hypertensive or diabetic patients were excluded. As a result, a low-risk population for ischemic heart disease has been selected. Moreover, changes in MV and MVG were not only observed in elderly patients but were progressive across the entire age span. This supports a physiologic age-related origin of DTI changes as reported in our study.
| Conclusions |
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Color M-mode DTI multilayer analysis may provide data on intramyocardial functional patterns and help to define the phenomena involved in normal aging. In our series of healthy volunteers, impact of age in protodiastolic myocardial function was irregular across left ventricular myocardial wall, defining a specific intramyocardial functional pattern related to normal aging. Besides, protodiastolic subendocardial peak velocities also showed the best correlation with protodiastolic peak mitral flow confirming that protodiastolic phenomena related to myocardial relaxation depends on the correct performance of subendocardium.
These data may call into question DTI studies ignoring the effect of age in diastolic intramyocardial function. An accurate definition of the normality pattern is required to establish a distinction between physiologic and pathologic processes. For this reason, age-related changes in intramyocardial function must be taken into account when evaluating DTI patterns in other settings in order to improve the clinical value of Doppler myocardial imaging parameters.
| Acknowledgements |
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We thank Dr. M Carazo (Cardiology Dept), C Allué, M Díaz and E Alberruche (Echo Lab) for their assistance. This work has been partially supported by grants from Comunidad de Madrid (III-PRICYT) and funds from a research contract with Acuson-Siemens.
| References |
|---|
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- Gerstenblith G., Frederiksen J., Yin F.C., Fortuin N.J., Lakatta E.G., Weisfeldt M.L. Echocardiographic assessment of a normal adult aging population. Circulation (1977) 56(2):273–278.
[Abstract/Free Full Text] - Yamada H., Oki T., Mishiro Y., Tabata T., Abe M., Onose Y., et al. Effect of aging on diastolic left ventricular myocardial velocities measured by pulsed tissue Doppler imaging in healthy subjects. J Am Soc Echocardiogr (1999) 12(7):574–581.[CrossRef][ISI][Medline]
- Onose Y., Oki T., Mishiro Y., Yamada H., Abe M., Manabe K., et al. Influence of aging on systolic left ventricular wall motion velocities along the long and short axes in clinically normal patients determined by pulsed tissue Doppler imaging. J Am Soc Echocardiogr (1999) 12(11):921–926.[CrossRef][ISI][Medline]
- Sun J.P., Popovic Z.B., Greenberg N.L., Xu X.F., Asher C.R., Stewart W.J., et al. Noninvasive quantification of regional myocardial function using Doppler-derived velocity, displacement, strain rate, and strain in healthy volunteers: effects of aging. J Am Soc Echocardiogr (2004) 17(2):132–138.[CrossRef][ISI][Medline]
- Kowalski M., Kukulski T., Jamal F., D'Hooge J., Weidemann F., Rademakers F., et al. Can natural strain and strain rate quantify regional myocardial deformation? A study in healthy subjects. Ultrasound Med Biol (2001) 27(8):1087–1097.[CrossRef][ISI][Medline]
- Ahmed S., Shapiro E.P., O'Connor F.E., Fleg J.L. Effect of normative aging on midwall left ventricular systolic performance. Am J Cardiol (2001) 88(11):1330–1334.[CrossRef][ISI][Medline]
- Slotwiner D.J., Devereux R.B., Schwartz J.E., Pickering T.G., de Simone G., Ganau A., et al. Relation of age to left ventricular function in clinically normal adults. Am J Cardiol (1998) 82(5):621–626.[CrossRef][ISI][Medline]
- Derumeaux G., Ovize M., Loufoua J., Pontier G., Andre-Fouet X., Cribier A. Assessment of nonuniformity of transmural myocardial velocities by color-coded tissue Doppler imaging: characterization of normal, ischemic, and stunned myocardium. Circulation (2000) 101(12):1390–1395.
[Abstract/Free Full Text] - Palka P., Lange A., Fleming A.D., Donnelly J.E., Dutka D.P., Starkey I.R., et al. Differences in myocardial velocity gradient measured throughout the cardiac cycle in patients with hypertrophic cardiomyopathy, athletes and patients with left ventricular hypertrophy due to hypertension. J Am Coll Cardiol (1997) 30(3):760–768.[Abstract]
- Garot J., Derumeaux G.A., Monin J.L., Duval-Moulin A.M., Simon M., Pascal D., et al. Quantitative systolic and diastolic transmyocardial velocity gradients assessed by M-mode colour Doppler tissue imaging as reliable indicators of regional left ventricular function after acute myocardial infarction. Eur Heart J (1999) 20(8):593–603.
[Abstract/Free Full Text] - Palka P., Lange A., Fleming A.D., Fenn L.N., Bouki K.P., Shaw T.R., et al. Age-related transmural peak mean velocities and peak velocity gradients by Doppler myocardial imaging in normal subjects. Eur Heart J (1996) 17(6):940–950.
[Abstract/Free Full Text] - Desco M., Antoranz J.C. Technical principles of Doppler tissue imaging. In: García-Fernández M.A. Zamorano J.L. Azevedo J. Doppler tissue imaging (1997) New York: McGraw-Hill.
- Desco M., Ledesma-Carbayo M.J., Perez E., Santos A., Antoranz J.C., Malpica N., et al. Assessment of normal and ischaemic myocardium by quantitative M-mode tissue Doppler imaging. Ultrasound Med Biol (2002) 28(5):561–569.[CrossRef][ISI][Medline]
- Fleming A.D., Xia X., McDicken W.N., Sutherland G.R., Fenn L. Myocardial velocity gradients detected by Doppler imaging. Br J Radiol (1994) 67(799):679–688.[Abstract]
- Zamorano J., Wallbridge D.R., Ge J., Drozd J., Nesser J., Erbel R. Non-invasive assessment of cardiac physiology by tissue Doppler echocardiography. A comparison with invasive haemodynamics. Eur Heart J (1997) 18(2):330–339.
[Abstract/Free Full Text] - Bland J.M., Altman D.G. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet (1986) 1(8476):307–310.[CrossRef][ISI][Medline]
- Gallagher K.P., Osakada G., Matsuzaki M., Miller M., Kemper W.S., Ross J. Jr. Nonuniformity of inner and outer systolic wall thickening in conscious dogs. Am J Physiol (1985) 249(2 Pt 2):H241–H248.[ISI][Medline]
- Sabbah H.N., Marzilli M., Stein P.D. The relative role of subendocardium and subepicardium in left ventricular mechanics. Am J Physiol (1981) 240(6):H920–H926.[ISI][Medline]
- Rijcken J., Bovendeerd P.H., Schoofs A.J., van Campen D.H., Arts T. Optimization of cardiac fiber orientation for homogeneous fiber strain during ejection. Ann Biomed Eng (1999) 27(3):289–297.[CrossRef][ISI][Medline]
- Arts T., Reneman R.S., Veenstra P.C. A model of the mechanics of the left ventricle. Ann Biomed Eng (1979) 7(3–4):299–318.[CrossRef][ISI][Medline]
- Schwartz A., Sordahl L.A., Entman M.L., Allen J.C., Reddy Y.S., Goldstein M.A., et al. Abnormal biochemistry in myocardial failure. Am J Cardiol (1973) 32(4):407–422.[CrossRef][ISI][Medline]
- Shimizu Y., Uematsu M., Shimizu H., Nakamura K., Yamagishi M., Miyatake K. Peak negative myocardial velocity gradient in early diastole as a noninvasive indicator of left ventricular diastolic function: comparison with transmitral flow velocity indices. J Am Coll Cardiol (1998) 32(5):1418–1425.
[Abstract/Free Full Text] - Weisfeldt M.L., Loeven W.A., Shock N.W. Resting and active mechanical properties of trabeculae carneae from aged male rats. Am J Physiol (1971) 220(6):1921–1927.
[Free Full Text] - Harrison T.R., Dixon K., Russell R.O., Bidwai P.S., Neal Coleman H. The relation of age to the duration of contraction, ejection and relaxation of the normal human heart. Am Heart J (1964) 67:189–199.[CrossRef][ISI][Medline]
- Henein M., Lindqvist P., Francis D., Morner S., Waldenstrom A., Kazzam E. Tissue Doppler analysis of age-dependency in diastolic ventricular behaviour and filling: a cross-sectional study of healthy hearts (the Umea General Population Heart Study). Eur Heart J (2002) 23(2):162–171.
[Abstract/Free Full Text] - Anversa P., Hiler B., Ricci R., Guideri G., Olivetti G. Myocyte cell loss and myocyte hypertrophy in the aging rat heart. J Am Coll Cardiol (1986) 8(6):1441–1448.[Abstract]
- Matsuzaki M., Tanaka N., Toma Y., Miura T., Katayama K., Ozaki M., et al. Effect of changing afterload and inotropic states on inner and outer ventricular wall thickening. Am J Physiol (1992) 263(1 Pt 2):H109–H116.[ISI][Medline]
- Chen C.H., Nakayama M., Nevo E., Fetics B.J., Maughan W.L., Kass D.A. Coupled systolic-ventricular and vascular stiffening with age: implications for pressure regulation and cardiac reserve in the elderly. J Am Coll Cardiol (1998) 32(5):1221–1227.
[Abstract/Free Full Text] - Mantero A., Gentile F., Gualtierotti C., Azzollini M., Barbier P., Beretta L., et al. Left ventricular diastolic parameters in 288 normal subjects from 20 to 80 years old. Eur Heart J (1995) 16(1):94–105.[Medline]
- Jones C.J., Raposo L., Gibson D.G. Functional importance of the long axis dynamics of the human left ventricle. Br Heart J (1990) 63(4):215–220.
[Abstract/Free Full Text] - Shirani J., Yousefi J., Roberts W.C. Major cardiac findings at necropsy in 366 American octogenarians. Am J Cardiol (1995) 75(2):151–156.[CrossRef][ISI][Medline]
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V, difference of velocity.

