- Email: [email protected]
Myocardial Radial Strain in Early Diastole is Useful for Assessing Left Ventricular Early Diastolic Function: Comparison with Invasive Parameters
LEFT VENTRICULAR FUNCTION
Myocardial Radial Strain in Early Diastole is Useful for Assessing Left Ventricular Early Diastolic Function: Comparison with Invasive Parameters Kazuaki Wakami, MD, Nobuyuki Ohte, MD, Seiichiro Sakata, MD, and Genjiro Kimura, MD, Nagoya, Japan
Background: Peak myocardial systolic strain determined using myocardial strain imaging is a useful index of left ventricular (LV) myocardial systolic function. We investigated the relationship between peak myocardial radial strain during early diastole and LV early diastolic function. Methods: A total of 85 patients without localized LV wall-motion abnormality underwent myocardial strain imaging and diagnostic cardiac catheterization. Peak myocardial radial strain during early diastole was obtained at the LV posterior-sided wall in the short-axis image. Invasive parameters of LV function were determined during cardiac catheterization. Results: Peak myocardial radial strain during early diastole significantly correlated with both the time constant (r ⫽ 0.80, P ⬍ .0001) and the peak negative dP/dt (r ⫽ ⫺0.64, P ⬍ .0001). Although it correlated with the LV ejection fraction, LV end-diastolic pressure, LV end-systolic volume index, and mean pulmonary capillary wedge pressure, the time constant was the prime determinant of peak myocardial radial strain during early diastole. Conclusion: Peak myocardial radial strain during early diastole could be used to evaluate LV early diastolic function. Myocardial strain imaging is a promising noninvasive tool for assessing LV function in systole and early diastole.
It is well established that left ventricular (LV) diastolic dysfunction is closely related to exercise intolerance and prognosis in patients with cardiac disease, despite patients’ range of LV systolic function.1-6 The newly developed technique of tissue strain imaging with Doppler echocardiography can demonstrate the transmural profiles of myocardial strain in the radial direction of the LV wall through a cardiac cycle.7 Although myocardial strain imaging has been used to evaluate local myocardial systolic function in the clinical setting,8-13 within our knowledge, no one has used this parameter to assess LV early diastolic function. Furthermore, despite the fact LV wall motion in the radial direction is particularly important for LV filling and ejection of blood to the aorta, the strain value in the radial direction in the LV has rarely been evaluated in relation to LV diastolic function. Accordingly, we hypothesized that LV dysfunction, which impairs LV pump performance, should be more readily observed in myocardial function in the radial direction. If so, myocardial strain imaging in the radial direction could be used to assess LV early diastolic function.
From the Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. Reprint requests: Nobuyuki Ohte, MD, Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan (E-mail: ohte@ med.nagoya-cu.ac.jp). 0894-7317/$34.00 Copyright 2008 by the American Society of Echocardiography. doi:10.1016/j.echo.2007.08.002
446
METHODS We studied 380 patients requiring evaluation for coronary artery disease who underwent cardiac catheterization including LV pressure measurement using a catheter-tipped micromanometer. From this group, we selected 85 patients who had no localized LV wall-motion abnormality at rest. Patients with primary valvular heart disease, atrial fibrillation, or intraventricular conduction disturbances were excluded from the study. Based on the results of cardiac catheterization and echocardiography, 12 patients were given the diagnosis of atypical chest pain, 18 of angina pectoris on exertion, and 9 of an electrocardiogram abnormality during exercise absent significant coronary stenosis. A total of 29 underwent re-evaluation of the coronary arteries after coronary intervention and showed no significant coronary stenosis. The remaining 17 patients were given the diagnosis of cardiomyopathy: 11 of nonischemic dilated cardiomyopathy and 6 of hypertrophic cardiomyopathy. Patients with angina pectoris had more than 75% stenosis in at least one of the 3 major coronary arteries but left ventriculography showed no LV wall-motion abnormality. They had no chest symptoms during the examination period. All patients continued to receive cardiac medications during the study. All provided written informed consent to participate, and the study was performed according to the regulations proposed by our ethical guidelines committee. Standard Doppler Echocardiography All ultrasound examinations were performed using a commercially available echocardiographic machine (Aplio80, Toshiba Medical Systems, Tokyo, Japan) with a 3-MHz transducer. Patients were examined at rest in the left lateral decubitus position. Transmitral flow
Journal of the American Society of Echocardiography Volume 21 Number 5
Wakami et al
447
velocities during early diastole (E) and atrial contraction (A) at the mitral orifice were obtained using pulsed Doppler echocardiography in the apical 4-chamber view. Pulsed Doppler imaging was also used to measure the peak mitral annular velocity during early diastole (Ea) at the septal corner of the mitral annulus. The ratio E/Ea, an index of LV filling pressure, was also calculated.14,15 We divided the patients into 4 groups based on their E/A ratio, the deceleration time of the E wave, and the E/Ea ratio using the criteria proposed by Redfield et al16 (normal LV filling pattern, abnormal relaxation LV filling pattern, pseudonormal LV filling pattern, or restrictive LV filling pattern). Myocardial Strain Imaging Digital cineloops of 2-dimensional Doppler tissue imaging (velocity imaging) during two cardiac cycles were acquired at the mid-LV level in the parasternal short-axis view and in the apical 4-chamber view. The range of frame rates used was 60 to 80/s. Myocardial strain was analyzed offline using an echo image analyzer (EchoAgent, Toshiba Medical Systems). All analyses were performed by the same observer blind to the cardiac catheterization data. Transmural myocardial strain profiles in the radial direction on the short-axis image were generated from myocardial velocity data as follows. The center of contraction in the LV short-axis image was visually and manually established at end diastole, and Doppler angle correction was used to instantaneously calculate myocardial velocities toward and away from the center throughout a cardiac cycle. The center defined at end diastole was applied throughout the cardiac cycle. Myocardial velocity data sets in the cardiac cycle were converted to myocardial displacement data sets using a tissue tracking method. Myocardial displacement data were differentiated on the basis of myocardial distance through the cardiac cycle and converted to myocardial strain data sets using the Lagrangian method.17 For measurements of radial strain, we used a 3-mm length for the initial differential distance. We obtained transmural strain profiles at the indexed phase along the 4-mm–wide M-mode sampling cursor that was aligned perpendicular to the LV wall on the LV short-axis strain images. This method for obtaining transmural strain profile was validated by Maruo et al7 in an experimental study in dogs. From the point of theoretic accuracy of the Doppler angle correction, we obtained myocardial radial strain data at the LV posterior-sided wall (150-230 degrees from the anterior wall viewed from the placed LV contraction center). We measured peak myocardial radial strain during early diastole on the M-mode strain profile as shown in Figure 1. Peak myocardial longitudinal strain during early diastole was also obtained at the mid-LV level of the septum in the apical 4-chamber image using the Lagrangian method,17 with an initial differential distance of 10 mm. We used a 5- ⫻ 5-mm square region of interest that was automatically tracked during diastole. Strain profiles in the LV longitudinal direction during diastole showed an inflection point at the end of early diastolic filling. Thus, early diastolic strain in the longitudinal direction was obtained at the inflection point where early diastolic filling switches to diastasis. Cardiac Catheterization Diagnostic cardiac catheterization was performed within 2 hours after Doppler imaging. Pulmonary capillary wedge pressure was obtained using a flow-directed pulmonary artery catheter. Before contrast material was injected into the LV or coronary artery, LV pressure was obtained using a catheter-tipped micromanometer (SPC-454D, Millar Instrument Co, Houston, TX) and recorded on a polygraph system (RMC-3000, Nihon Kohden Inc, Tokyo, Japan).
Figure 1 Representative example of measurement of peak myocardial radial strain during early diastole. (A), Color presentation of M-mode myocardial radial strain during diastole on left ventricular (LV) inferior wall. Green lines on M-mode image represent traces of endocardium and epicardium obtained using tissue tracking method during diastole. Red line shows trace of red dot, which represents location of myocardium having peak radial strain value. (B), Computed transmural myocardial radial strain profile at indexed phase, shown as vertical yellow line on M-mode strain tracing presented in A. Profile is automatically drawn at indicated phase during diastole. (C), Temporal change in highest myocardial radial strain value in LV inferior wall during diastole. Point of interest that has highest myocardial strain value in LV inferior wall at indexed phase is easily identified on transmural myocardial radial strain profile, as shown in B. Point of highest strain value, such as red dot shown in A, is automatically traced using tissue tracking method during diastole. Then, temporal change of highest myocardial radial strain value is drawn as C. As shown in this graph, peak myocardial radial strain during early diastole is obtained at inflection point where early rapid filling switches to diastasis. ECG, Electrocardiogram.
From the recorded pressure waves, peak negative dP/dt and LV end-diastolic pressure were determined, and the time constant of LV pressure decay during isovolumic relaxation, , was calculated using the method of Weiss et al.18 Immediately after pressure measurements, biplane contrast left ventriculography was performed. LV end-systolic and end-diastolic volumes were calculated using a cardiac image analyzer and the method of Chapman et al.19 The LV ejection fraction was then determined. To normalize body size, LV end-systolic and end-diastolic volumes were divided by the body surface area of each patient and expressed as LV end-systolic and end-diastolic volume indexes. Regional LV wall motion was evaluated using the centerline method,20,21 a reliable means for assessing LV regional wall motion by contrast left ventriculography. Regions with more than 25% impairment of LV wall motion amplitude compared with the adjacent segments, which were based on the 7 segments of the American Heart Association, were defined as having local LV wall-motion abnormality.
448 Wakami et al
Journal of the American Society of Echocardiography May 2008
Table 1 Patient clinical characteristics and cardiac catheterization data Variable
Value (range)
Age, y Male, % Heart rate, beats/min Mean arterial pressure, mm Hg , ms Peak negative dP/dt, mm Hg/s LV ejection fraction, % LV end-diastolic volume index, mL/m2 LV end-systolic volume index, mL/m2 LV end-diastolic pressure, mm Hg Mean pulmonary capillary wedge pressure, mm Hg E, cm/s A, cm/s E/A velocity ratio Ea, cm/s E/Ea
66 ⫾ 11 (21-84) 73 69 ⫾ 13 (42-98) 101 ⫾ 15 (69-140) 44.1 ⫾ 8.4 (25.4-66.1) 1980 ⫾ 520 (1020-3310) 68 ⫾ 13 (22-84) 81 ⫾ 24 (50-175) 29 ⫾ 23 (10-128) 14.0 ⫾ 4.4 (5-27) 8.6 ⫾ 5.1 (2-26) 67.6 75.3 1.00 7.3 10.1
⫾ ⫾ ⫾ ⫾ ⫾
17.1 (34-134) 19.7 (22-120) 0.59 (0.46-4.69) 1.9 (1.6-12.5) 5.4 (3.4-48)
A, Peak transmitral flow velocity during atrial contraction; dP/dt, first derivative of left ventricular pressure; E, peak transmitral flow velocity during early diastole; Ea, mitral annular velocity during early diastole; LV, left ventricular; , time constant of left ventricular pressure decay. Data are means ⫾ SD.
Reproducibility of the Measurements Bland-Altman analysis22 was used to evaluate the reproducibility of measurements obtained by two separate observers and of measurements made by single observers across two separate occasions. For measurements of peak myocardial radial strain during early diastole obtained from 25 randomly selected patients, Bland-Altman analysis showed only a small bias of 1.6% and a limit of agreement of 15% between the two single-observer measurements of peak myocardial radial strain. Bland-Altman analysis also indicated a small bias of ⫺2.1% and a limit of agreement of 21% between two measurements by two independent observers. Statistical Analysis Data are expressed as the mean ⫾ SD. Differences among the 4 groups were evaluated using one-way analysis of variance with Bonferroni adjustment. Relationships between two parameters were evaluated using univariate linear regression analysis. In addition, stepwise multivariate regression analysis was used to determine which independent variables significantly affect the peak myocardial radial strain during early diastole. Analysis of covariance was used to evaluate the effect of LV ejection fraction on the relationship between the time constant and peak myocardial radial strain during early diastole. Differences with P values less than .05 were considered significant. RESULTS Patient characteristics and cardiac catheterization data are shown in Table 1. Peak myocardial radial strain during early diastole ranged from ⫺22% to ⫺63%. Univariate regression analysis revealed a significant positive correlation between peak myocardial radial strain during early diastole and the time constant of LV
relaxation (r ⫽ 0.80, P ⬍ .0001) and a significant inverse correlation between peak myocardial radial strain during early diastole and peak negative dP/dt (r ⫽ ⫺0.64, P ⬍ .0001) (Figure 2). Thus, despite the difference in patients’ transmitral flow patterns, peak myocardial radial strain values during early diastole were closely correlated to their time constant and peak negative dP/dt. Peak myocardial radial strain during early diastole was significantly correlated with the time constant in patients with preserved LV systolic function (LV ejection fraction ⱖ 55%; r ⫽ 0.80, P ⬍ .0001, n ⫽ 74) and in patients with reduced LV systolic function (LV ejection fraction ⬍ 55%; r ⫽ 0.75, P ⫽ .007, n ⫽ 11). The slopes of the two regression lines were not significantly different between patient groups with preserved and reduced LV systolic function (P ⫽ .14; analysis of covariance), suggesting that LV systolic function did not affect the relationship between peak myocardial radial strain during early diastole and . Peak myocardial radial strain values classified by the transmitral flow velocity patterns are shown in Figure 3. Analysis of variance demonstrated significant group differences in the peak myocardial radial strain during early diastole (⫺49 ⫾ 6.0% normal filling pattern vs ⫺40 ⫾ 7.6% abnormal relaxation filling pattern vs ⫺35 ⫾ 7.3% pseudonormal filling pattern vs ⫺28 ⫾ 4.0% restrictive filling pattern, P ⬍ .0001). Peak myocardial radial strain during early diastole decreased according to the progressive deterioration of LV diastolic function, which was assessed based on the transmitral flow velocity pattern (Figure 4). There were also weak but significant correlations between the peak myocardial radial strain during early diastole and the LV ejection fraction, LV end-diastolic volume index, LV end-systolic volume index, LV end-diastolic pressure, and mean pulmonary capillary wedge pressure (Figure 5 and Table 2). Multivariate regression analysis identified the time constant of LV relaxation and age as determinants of the peak myocardial radial strain during early diastole (r ⫽ 0.82, P ⬍ .0001) (Table 2). The time constant was the primary determinant. Peak myocardial longitudinal strain during early diastole ranged between 1.0% and 21.5% and was significantly and inversely correlated with the time constant (r ⫽ ⫺0.47, P ⬍ .0001). The correlation coefficient was rather lower than that characterizing the relationship between peak myocardial radial strain during early diastole and the time constant . Analysis of the relationship between conventional Doppler parameters for LV diastolic function and invasive indexes of LV diastolic function revealed that Ea but not the E/A ratio of transmitral flow significantly correlated with (r ⫽ ⫺0.59, P ⬍ .0001 and r ⫽ ⫺0.23, P ⫽ .051, respectively). The E/Ea ratio also significantly correlated with and the mean pulmonary capillary wedge pressure (r ⫽ 0.45, P ⬍ .0001 and r ⫽ 0.69, P ⬍ .0001, respectively). DISCUSSION The current study demonstrates that peak myocardial radial strain during early diastole is significantly and more closely correlated with the LV relaxation time constant than is peak myocardial longitudinal strain. Thus, we advocate evaluation of myocardial strain during early diastole in the radial direction as an index of LV early diastolic function. Comparison with Conventional Doppler Parameters Several investigators have demonstrated that mitral annular velocity during early diastole, Ea, is significantly correlated with the time
Journal of the American Society of Echocardiography Volume 21 Number 5
Wakami et al
449
Figure 2 Relationships between peak myocardial radial strain during early diastole and time constant (A) and peak negative dP/dt (B). Peak myocardial radial strain during early diastole became smaller (negative in value) with deterioration of left ventricular (LV) relaxation, irrespective of differences in LV diastolic filling pattern. Circle, Normal filing pattern; square, pseudonormal filling pattern; triangle, abnormal relaxation filling pattern; X, restrictive filling pattern.
Figure 3 Lack of effect of left ventricular (LV) systolic function on relationship between peak myocardial radial strain during early diastole and LV relaxation time constant . Circle, Patients having LV ejection fraction (LVEF) greater than or equal to 55%; triangle, patients having LVEF less than 55%. constant of LV pressure decay, which is the most crucial index of LV relaxation. Based on this relationship, Ea has been used to evaluate LV early diastolic function.23-26 Furthermore, in combination with transmitral E, E/Ea has been used to estimate LV filling pressure in clinical practice.14,15 In patients with hypertension or diabetes, subendocardial fibers are more likely to be affected by microvascular ischemia, causing deterioration of longitudinal myocardial contraction without obvious global LV dysfunction in the early stage of diseases.27 However, the most important role of the LV is that of a pump ejecting blood into the aorta. Thus, myocardial contraction and relaxation in the radial direction is considered crucial from the standpoint of LV blood filling and ejection. As shown in this study, the
Figure 4 Peak myocardial radial strain during early diastole with different types of transmitral flow velocity patterns. Significant differences in strain values were demonstrated for different filling patterns. (A), Normal filling pattern; (B), abnormal relaxation filling pattern; (C), pseudonormal filling pattern; (D), restrictive filling pattern. peak myocardial radial strain value during early diastole is rather higher than the peak myocardial longitudinal strain value, indicating an important role of myocardial radial strain in the volume change of the LV. Our finding of a relatively tighter correlation between peak myocardial radial strain during early diastole and versus peak myocardial longitudinal strain during early diastole and suggests that peak myocardial radial strain during early diastole may be superior to other Doppler imaging parameters for the noninvasive estimation of LV early diastolic function. Relationship Between Characteristics of Myocardial Radial Strain During Early Diastole and Cardiac Mechanics There was also a significant correlation between peak myocardial radial strain during early diastole and LV systolic function parameters such as the LV end-systolic volume index and LV ejection fraction. From the viewpoint of cardiac mechanics, Gilbert and Glantz28
450 Wakami et al
Journal of the American Society of Echocardiography May 2008
Figure 5 Relationships between peak myocardial radial strain during early diastole and mean pulmonary capillary wedge pressure (PCWP), left ventricular (LV) end-diastolic pressure (LVEDP), LV ejection fraction (LVEF), and LV end-systolic volume index (LVESVI). (A), Peak myocardial radial strain during early diastole decreased with increasing mean PCWP. (B), Peak myocardial radial strain during early diastole decreased with increasing LVEDP. (C), Peak myocardial radial strain during early diastole decreased with progressive impairment of LVEF. (D), Peak myocardial radial strain during early diastole decreased with increase in LVESVI. Table 2 Results of univariate and multivariate regression analyses of peak myocardial radial strain during early diastole Univariate
Multivariate
Variable
Correlation coefficient
P value
Age, y Heart rate, beats/min Mean arterial pressure, mm Hg , ms Peak negative dP/dt, mm Hg/s LV ejection fraction, % LV end-diastolic volume index, mL/m2 LV end-systolic volume index, mL/m2 LV end-diastolic pressure, mm Hg Mean pulmonary capillary wedge pressure, mm Hg
0.17 –0.20 0.065 0.80 –0.64 –0.36 0.35 0.37 0.56 0.57
.12 .061 .56 ⬍.0001 ⬍.0001 .0007 .0009 .0005 ⬍.0001 ⬍.0001
Beta coefficient
P value
0.15
.015
0.83
⬍.0001
dP/dt, First derivative of left ventricular pressure; LV, left ventricular; , time constant of left ventricular pressure decay.
reported that LVs with good systolic function have relatively smaller LV end-systolic volumes, producing a greater magnitude of LV rearrangement at early diastole through release of elastic energy stored during systole and hastening of LV relaxation. Thus, we propose that peak myocardial radial strain during early diastole reflects the mechanical nature of LV behavior over end systole to early diastole, as shown previously. Limitations Technical limitations prevented us from measuring peak myocardial radial strain during early diastole on the anterior or septal LV wall during early diastole. The right ventricle might have affected acquisi-
tion of the strain profile of the LV anterior-sided wall using the Lagrangian procedure, which requires complex calculation. Thus, we selected patients without LV motion abnormality. This may present problems for application of this method to patients with LV asynergy. Nevertheless, we believe that our findings are relevant to the noninvasive assessment of LV early diastolic function in patients without LV asynergy and that they increase the understanding of the importance of myocardial radial strain during early diastole. Conclusion The current study indicates that peak myocardial radial strain during early diastole can be used to evaluate LV early diastolic function without
Journal of the American Society of Echocardiography Volume 21 Number 5
consideration of the pseudonormalization that is observed in the transmitral flow velocity pattern with high LV filling pressure. Myocardial strain imaging in the radial direction is a promising noninvasive tool for assessing LV function in systole and early diastole. REFERENCES 1. Senni M, Tribouilloy CM, Rodeheffer RJ, Jacobsen SJ, Evans JM, Bailey KR, et al. Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation 1998;98:2282-9. 2. Kitzman DW, Little WC, Brubaker PH, Anderson RT, Hundley WG, Marburger CT, et al. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA 2002;288:2144-50. 3. Packer M. Abnormalities of diastolic function as a potential cause of exercise intolerance in chronic heart failure. Circulation 1990;81:III7886. 4. Davies SW, Fussell AL, Jordan SL, Poole-Wilson PA, Lipkin DP. Abnormal diastolic filling patterns in chronic heart failure–relationship to exercise capacity. Eur Heart J 1992;13:749-57. 5. Wheeldon NM, Clarkson P, MacDonald TM. Diastolic heart failure. Eur Heart J 1994;15:1689-97. 6. Little WC, Kitzman DW, Cheng CP. Diastolic dysfunction as a cause of exercise intolerance. Heart Fail Rev 2000;5:301-6. 7. Maruo T, Nakatani S, Jin Y, Uemura K, Sugimachi M, Ueda-Ishibashi H, et al. Evaluation of transmural distribution of viable muscle by myocardial strain profile and dobutamine stress echocardiography. Am J Physiol Heart Circ Physiol 2007;292:H921-7. 8. Armstrong G, Pasquet A, Fukamachi K, Cardon L, Olstad B, Marwick TH. Use of peak systolic strain as an index of regional left ventricular function: comparison with tissue Doppler velocity during dobutamine stress and myocardial ischemia. J Am Soc Echocardiogr 2000;13:731-7. 9. Urheim S, Edvardsen T, Torp H, Angelsen B, Smiseth OA. Myocardial strain by Doppler echocardiography: validation of a new method to quantify regional myocardial function. Circulation 2000;102:1158-64. 10. Edvardsen T, Skulstad H, Aakhus S, Urheim S, Ihlen H. Regional myocardial systolic function during acute myocardial ischemia assessed by strain Doppler echocardiography. J Am Coll Cardiol 2001;37:726-30. 11. Abraham TP, Nishimura RA. Myocardial strain: can we finally measure contractility? J Am Coll Cardiol 2001;37:731-4. 12. Koyama J, Ray-Sequin PA, Falk RH. Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis. Circulation 2003;107:2446-52. 13. Leitman M, Lysyansky P, Sidenko S, Shir V, Peleg E, Binenbaum M, et al. Two-dimensional strain–a novel software for real-time quantitative echocardiographic assessment of myocardial function. J Am Soc Echocardiogr 2004;17:1021-9.
Wakami et al
451
14. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997;30:1527-33. 15. Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 2000;102:1788-94. 16. Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 2003;289:194-202. 17. D’hooge J, Heimdal A, Jamal F, Kukulski T, Bijnens B, Rademakers F, et al. Regional strain and strain rate measurements by cardiac ultrasound: principles, implementation and limitations. Eur J Echocardiogr 2000;1: 154-70. 18. Weiss JL, Frederiksen JW, Weisfeldt ML. Hemodynamic determinants of the time-course of fall in canine left ventricular pressure. J Clin Invest 1976;58:751-60. 19. Chapman CB, Baker O, Reynolds J, Bonte FJ. Use of biplane cinefluorography for measurement of ventricular volume. Circulation 1958;18: 1105-17. 20. Sheehan FH, Bolson EL, Dodge HT, Mathey DG, Schofer J, Woo HW. Advantages and applications of centerline method for characterizing regional ventricular function. Circulation 1986;74:293-305. 21. Yoshida T, Ohte N, Narita H, Sakata S, Wakami K, Asada K, et al. Lack of inertia force of late systolic aortic flow is a cause of left ventricular isolated diastolic dysfunction in patients with coronary artery disease. J Am Coll Cardiol 2006;48:983-91. 22. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307-10. 23. Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 1997;30:474-80. 24. Oki T, Tabata T, Yamada H, Wakatsuki T, Shinohara H, Nishikado A, et al. Clinical application of pulsed Doppler tissue imaging for assessing abnormal left ventricular relaxation. Am J Cardiol 1997;79:921-8. 25. Ohte N, Narita H, Hashimoto T, Akita S, Kurokawa K, Fujinami T. Evaluation of left ventricular early diastolic performance by color tissue Doppler imaging of the mitral annulus. Am J Cardiol 1998;82:1414-7. 26. Nagueh SF, Sun H, Kopelen HA, Middleton KJ, Khoury DS. Hemodynamic determinants of the mitral annulus diastolic velocities by tissue Doppler. J Am Coll Cardiol 2001;37:278-85. 27. Vinereanu D, Nicolaides E, Tweddel AC, Mädler CF, Holst B, Boden LE, et al. Subclinical left ventricular dysfunction in asymptomatic patients with type 2 diabetes mellitus, related to serum lipids and glycated hemoglobin. Clin Sci (Colch) 2003;105;591-9. 28. Gilbert JC, Glantz SA. Determinants of left ventricular filling and of the diastolic pressure-volume relation. Circ Res 1989;64:827-52.
Myocardial Radial Strain in Early Diastole is Useful for Assessing Left Ventricular Early Diastolic Function: Comparison with Invasive Parameters Kazuaki Wakami, MD, Nobuyuki Ohte, MD, Seiichiro Sakata, MD, and Genjiro Kimura, MD, Nagoya, Japan
Background: Peak myocardial systolic strain determined using myocardial strain imaging is a useful index of left ventricular (LV) myocardial systolic function. We investigated the relationship between peak myocardial radial strain during early diastole and LV early diastolic function. Methods: A total of 85 patients without localized LV wall-motion abnormality underwent myocardial strain imaging and diagnostic cardiac catheterization. Peak myocardial radial strain during early diastole was obtained at the LV posterior-sided wall in the short-axis image. Invasive parameters of LV function were determined during cardiac catheterization. Results: Peak myocardial radial strain during early diastole significantly correlated with both the time constant (r ⫽ 0.80, P ⬍ .0001) and the peak negative dP/dt (r ⫽ ⫺0.64, P ⬍ .0001). Although it correlated with the LV ejection fraction, LV end-diastolic pressure, LV end-systolic volume index, and mean pulmonary capillary wedge pressure, the time constant was the prime determinant of peak myocardial radial strain during early diastole. Conclusion: Peak myocardial radial strain during early diastole could be used to evaluate LV early diastolic function. Myocardial strain imaging is a promising noninvasive tool for assessing LV function in systole and early diastole.
It is well established that left ventricular (LV) diastolic dysfunction is closely related to exercise intolerance and prognosis in patients with cardiac disease, despite patients’ range of LV systolic function.1-6 The newly developed technique of tissue strain imaging with Doppler echocardiography can demonstrate the transmural profiles of myocardial strain in the radial direction of the LV wall through a cardiac cycle.7 Although myocardial strain imaging has been used to evaluate local myocardial systolic function in the clinical setting,8-13 within our knowledge, no one has used this parameter to assess LV early diastolic function. Furthermore, despite the fact LV wall motion in the radial direction is particularly important for LV filling and ejection of blood to the aorta, the strain value in the radial direction in the LV has rarely been evaluated in relation to LV diastolic function. Accordingly, we hypothesized that LV dysfunction, which impairs LV pump performance, should be more readily observed in myocardial function in the radial direction. If so, myocardial strain imaging in the radial direction could be used to assess LV early diastolic function.
From the Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. Reprint requests: Nobuyuki Ohte, MD, Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan (E-mail: ohte@ med.nagoya-cu.ac.jp). 0894-7317/$34.00 Copyright 2008 by the American Society of Echocardiography. doi:10.1016/j.echo.2007.08.002
446
METHODS We studied 380 patients requiring evaluation for coronary artery disease who underwent cardiac catheterization including LV pressure measurement using a catheter-tipped micromanometer. From this group, we selected 85 patients who had no localized LV wall-motion abnormality at rest. Patients with primary valvular heart disease, atrial fibrillation, or intraventricular conduction disturbances were excluded from the study. Based on the results of cardiac catheterization and echocardiography, 12 patients were given the diagnosis of atypical chest pain, 18 of angina pectoris on exertion, and 9 of an electrocardiogram abnormality during exercise absent significant coronary stenosis. A total of 29 underwent re-evaluation of the coronary arteries after coronary intervention and showed no significant coronary stenosis. The remaining 17 patients were given the diagnosis of cardiomyopathy: 11 of nonischemic dilated cardiomyopathy and 6 of hypertrophic cardiomyopathy. Patients with angina pectoris had more than 75% stenosis in at least one of the 3 major coronary arteries but left ventriculography showed no LV wall-motion abnormality. They had no chest symptoms during the examination period. All patients continued to receive cardiac medications during the study. All provided written informed consent to participate, and the study was performed according to the regulations proposed by our ethical guidelines committee. Standard Doppler Echocardiography All ultrasound examinations were performed using a commercially available echocardiographic machine (Aplio80, Toshiba Medical Systems, Tokyo, Japan) with a 3-MHz transducer. Patients were examined at rest in the left lateral decubitus position. Transmitral flow
Journal of the American Society of Echocardiography Volume 21 Number 5
Wakami et al
447
velocities during early diastole (E) and atrial contraction (A) at the mitral orifice were obtained using pulsed Doppler echocardiography in the apical 4-chamber view. Pulsed Doppler imaging was also used to measure the peak mitral annular velocity during early diastole (Ea) at the septal corner of the mitral annulus. The ratio E/Ea, an index of LV filling pressure, was also calculated.14,15 We divided the patients into 4 groups based on their E/A ratio, the deceleration time of the E wave, and the E/Ea ratio using the criteria proposed by Redfield et al16 (normal LV filling pattern, abnormal relaxation LV filling pattern, pseudonormal LV filling pattern, or restrictive LV filling pattern). Myocardial Strain Imaging Digital cineloops of 2-dimensional Doppler tissue imaging (velocity imaging) during two cardiac cycles were acquired at the mid-LV level in the parasternal short-axis view and in the apical 4-chamber view. The range of frame rates used was 60 to 80/s. Myocardial strain was analyzed offline using an echo image analyzer (EchoAgent, Toshiba Medical Systems). All analyses were performed by the same observer blind to the cardiac catheterization data. Transmural myocardial strain profiles in the radial direction on the short-axis image were generated from myocardial velocity data as follows. The center of contraction in the LV short-axis image was visually and manually established at end diastole, and Doppler angle correction was used to instantaneously calculate myocardial velocities toward and away from the center throughout a cardiac cycle. The center defined at end diastole was applied throughout the cardiac cycle. Myocardial velocity data sets in the cardiac cycle were converted to myocardial displacement data sets using a tissue tracking method. Myocardial displacement data were differentiated on the basis of myocardial distance through the cardiac cycle and converted to myocardial strain data sets using the Lagrangian method.17 For measurements of radial strain, we used a 3-mm length for the initial differential distance. We obtained transmural strain profiles at the indexed phase along the 4-mm–wide M-mode sampling cursor that was aligned perpendicular to the LV wall on the LV short-axis strain images. This method for obtaining transmural strain profile was validated by Maruo et al7 in an experimental study in dogs. From the point of theoretic accuracy of the Doppler angle correction, we obtained myocardial radial strain data at the LV posterior-sided wall (150-230 degrees from the anterior wall viewed from the placed LV contraction center). We measured peak myocardial radial strain during early diastole on the M-mode strain profile as shown in Figure 1. Peak myocardial longitudinal strain during early diastole was also obtained at the mid-LV level of the septum in the apical 4-chamber image using the Lagrangian method,17 with an initial differential distance of 10 mm. We used a 5- ⫻ 5-mm square region of interest that was automatically tracked during diastole. Strain profiles in the LV longitudinal direction during diastole showed an inflection point at the end of early diastolic filling. Thus, early diastolic strain in the longitudinal direction was obtained at the inflection point where early diastolic filling switches to diastasis. Cardiac Catheterization Diagnostic cardiac catheterization was performed within 2 hours after Doppler imaging. Pulmonary capillary wedge pressure was obtained using a flow-directed pulmonary artery catheter. Before contrast material was injected into the LV or coronary artery, LV pressure was obtained using a catheter-tipped micromanometer (SPC-454D, Millar Instrument Co, Houston, TX) and recorded on a polygraph system (RMC-3000, Nihon Kohden Inc, Tokyo, Japan).
Figure 1 Representative example of measurement of peak myocardial radial strain during early diastole. (A), Color presentation of M-mode myocardial radial strain during diastole on left ventricular (LV) inferior wall. Green lines on M-mode image represent traces of endocardium and epicardium obtained using tissue tracking method during diastole. Red line shows trace of red dot, which represents location of myocardium having peak radial strain value. (B), Computed transmural myocardial radial strain profile at indexed phase, shown as vertical yellow line on M-mode strain tracing presented in A. Profile is automatically drawn at indicated phase during diastole. (C), Temporal change in highest myocardial radial strain value in LV inferior wall during diastole. Point of interest that has highest myocardial strain value in LV inferior wall at indexed phase is easily identified on transmural myocardial radial strain profile, as shown in B. Point of highest strain value, such as red dot shown in A, is automatically traced using tissue tracking method during diastole. Then, temporal change of highest myocardial radial strain value is drawn as C. As shown in this graph, peak myocardial radial strain during early diastole is obtained at inflection point where early rapid filling switches to diastasis. ECG, Electrocardiogram.
From the recorded pressure waves, peak negative dP/dt and LV end-diastolic pressure were determined, and the time constant of LV pressure decay during isovolumic relaxation, , was calculated using the method of Weiss et al.18 Immediately after pressure measurements, biplane contrast left ventriculography was performed. LV end-systolic and end-diastolic volumes were calculated using a cardiac image analyzer and the method of Chapman et al.19 The LV ejection fraction was then determined. To normalize body size, LV end-systolic and end-diastolic volumes were divided by the body surface area of each patient and expressed as LV end-systolic and end-diastolic volume indexes. Regional LV wall motion was evaluated using the centerline method,20,21 a reliable means for assessing LV regional wall motion by contrast left ventriculography. Regions with more than 25% impairment of LV wall motion amplitude compared with the adjacent segments, which were based on the 7 segments of the American Heart Association, were defined as having local LV wall-motion abnormality.
448 Wakami et al
Journal of the American Society of Echocardiography May 2008
Table 1 Patient clinical characteristics and cardiac catheterization data Variable
Value (range)
Age, y Male, % Heart rate, beats/min Mean arterial pressure, mm Hg , ms Peak negative dP/dt, mm Hg/s LV ejection fraction, % LV end-diastolic volume index, mL/m2 LV end-systolic volume index, mL/m2 LV end-diastolic pressure, mm Hg Mean pulmonary capillary wedge pressure, mm Hg E, cm/s A, cm/s E/A velocity ratio Ea, cm/s E/Ea
66 ⫾ 11 (21-84) 73 69 ⫾ 13 (42-98) 101 ⫾ 15 (69-140) 44.1 ⫾ 8.4 (25.4-66.1) 1980 ⫾ 520 (1020-3310) 68 ⫾ 13 (22-84) 81 ⫾ 24 (50-175) 29 ⫾ 23 (10-128) 14.0 ⫾ 4.4 (5-27) 8.6 ⫾ 5.1 (2-26) 67.6 75.3 1.00 7.3 10.1
⫾ ⫾ ⫾ ⫾ ⫾
17.1 (34-134) 19.7 (22-120) 0.59 (0.46-4.69) 1.9 (1.6-12.5) 5.4 (3.4-48)
A, Peak transmitral flow velocity during atrial contraction; dP/dt, first derivative of left ventricular pressure; E, peak transmitral flow velocity during early diastole; Ea, mitral annular velocity during early diastole; LV, left ventricular; , time constant of left ventricular pressure decay. Data are means ⫾ SD.
Reproducibility of the Measurements Bland-Altman analysis22 was used to evaluate the reproducibility of measurements obtained by two separate observers and of measurements made by single observers across two separate occasions. For measurements of peak myocardial radial strain during early diastole obtained from 25 randomly selected patients, Bland-Altman analysis showed only a small bias of 1.6% and a limit of agreement of 15% between the two single-observer measurements of peak myocardial radial strain. Bland-Altman analysis also indicated a small bias of ⫺2.1% and a limit of agreement of 21% between two measurements by two independent observers. Statistical Analysis Data are expressed as the mean ⫾ SD. Differences among the 4 groups were evaluated using one-way analysis of variance with Bonferroni adjustment. Relationships between two parameters were evaluated using univariate linear regression analysis. In addition, stepwise multivariate regression analysis was used to determine which independent variables significantly affect the peak myocardial radial strain during early diastole. Analysis of covariance was used to evaluate the effect of LV ejection fraction on the relationship between the time constant and peak myocardial radial strain during early diastole. Differences with P values less than .05 were considered significant. RESULTS Patient characteristics and cardiac catheterization data are shown in Table 1. Peak myocardial radial strain during early diastole ranged from ⫺22% to ⫺63%. Univariate regression analysis revealed a significant positive correlation between peak myocardial radial strain during early diastole and the time constant of LV
relaxation (r ⫽ 0.80, P ⬍ .0001) and a significant inverse correlation between peak myocardial radial strain during early diastole and peak negative dP/dt (r ⫽ ⫺0.64, P ⬍ .0001) (Figure 2). Thus, despite the difference in patients’ transmitral flow patterns, peak myocardial radial strain values during early diastole were closely correlated to their time constant and peak negative dP/dt. Peak myocardial radial strain during early diastole was significantly correlated with the time constant in patients with preserved LV systolic function (LV ejection fraction ⱖ 55%; r ⫽ 0.80, P ⬍ .0001, n ⫽ 74) and in patients with reduced LV systolic function (LV ejection fraction ⬍ 55%; r ⫽ 0.75, P ⫽ .007, n ⫽ 11). The slopes of the two regression lines were not significantly different between patient groups with preserved and reduced LV systolic function (P ⫽ .14; analysis of covariance), suggesting that LV systolic function did not affect the relationship between peak myocardial radial strain during early diastole and . Peak myocardial radial strain values classified by the transmitral flow velocity patterns are shown in Figure 3. Analysis of variance demonstrated significant group differences in the peak myocardial radial strain during early diastole (⫺49 ⫾ 6.0% normal filling pattern vs ⫺40 ⫾ 7.6% abnormal relaxation filling pattern vs ⫺35 ⫾ 7.3% pseudonormal filling pattern vs ⫺28 ⫾ 4.0% restrictive filling pattern, P ⬍ .0001). Peak myocardial radial strain during early diastole decreased according to the progressive deterioration of LV diastolic function, which was assessed based on the transmitral flow velocity pattern (Figure 4). There were also weak but significant correlations between the peak myocardial radial strain during early diastole and the LV ejection fraction, LV end-diastolic volume index, LV end-systolic volume index, LV end-diastolic pressure, and mean pulmonary capillary wedge pressure (Figure 5 and Table 2). Multivariate regression analysis identified the time constant of LV relaxation and age as determinants of the peak myocardial radial strain during early diastole (r ⫽ 0.82, P ⬍ .0001) (Table 2). The time constant was the primary determinant. Peak myocardial longitudinal strain during early diastole ranged between 1.0% and 21.5% and was significantly and inversely correlated with the time constant (r ⫽ ⫺0.47, P ⬍ .0001). The correlation coefficient was rather lower than that characterizing the relationship between peak myocardial radial strain during early diastole and the time constant . Analysis of the relationship between conventional Doppler parameters for LV diastolic function and invasive indexes of LV diastolic function revealed that Ea but not the E/A ratio of transmitral flow significantly correlated with (r ⫽ ⫺0.59, P ⬍ .0001 and r ⫽ ⫺0.23, P ⫽ .051, respectively). The E/Ea ratio also significantly correlated with and the mean pulmonary capillary wedge pressure (r ⫽ 0.45, P ⬍ .0001 and r ⫽ 0.69, P ⬍ .0001, respectively). DISCUSSION The current study demonstrates that peak myocardial radial strain during early diastole is significantly and more closely correlated with the LV relaxation time constant than is peak myocardial longitudinal strain. Thus, we advocate evaluation of myocardial strain during early diastole in the radial direction as an index of LV early diastolic function. Comparison with Conventional Doppler Parameters Several investigators have demonstrated that mitral annular velocity during early diastole, Ea, is significantly correlated with the time
Journal of the American Society of Echocardiography Volume 21 Number 5
Wakami et al
449
Figure 2 Relationships between peak myocardial radial strain during early diastole and time constant (A) and peak negative dP/dt (B). Peak myocardial radial strain during early diastole became smaller (negative in value) with deterioration of left ventricular (LV) relaxation, irrespective of differences in LV diastolic filling pattern. Circle, Normal filing pattern; square, pseudonormal filling pattern; triangle, abnormal relaxation filling pattern; X, restrictive filling pattern.
Figure 3 Lack of effect of left ventricular (LV) systolic function on relationship between peak myocardial radial strain during early diastole and LV relaxation time constant . Circle, Patients having LV ejection fraction (LVEF) greater than or equal to 55%; triangle, patients having LVEF less than 55%. constant of LV pressure decay, which is the most crucial index of LV relaxation. Based on this relationship, Ea has been used to evaluate LV early diastolic function.23-26 Furthermore, in combination with transmitral E, E/Ea has been used to estimate LV filling pressure in clinical practice.14,15 In patients with hypertension or diabetes, subendocardial fibers are more likely to be affected by microvascular ischemia, causing deterioration of longitudinal myocardial contraction without obvious global LV dysfunction in the early stage of diseases.27 However, the most important role of the LV is that of a pump ejecting blood into the aorta. Thus, myocardial contraction and relaxation in the radial direction is considered crucial from the standpoint of LV blood filling and ejection. As shown in this study, the
Figure 4 Peak myocardial radial strain during early diastole with different types of transmitral flow velocity patterns. Significant differences in strain values were demonstrated for different filling patterns. (A), Normal filling pattern; (B), abnormal relaxation filling pattern; (C), pseudonormal filling pattern; (D), restrictive filling pattern. peak myocardial radial strain value during early diastole is rather higher than the peak myocardial longitudinal strain value, indicating an important role of myocardial radial strain in the volume change of the LV. Our finding of a relatively tighter correlation between peak myocardial radial strain during early diastole and versus peak myocardial longitudinal strain during early diastole and suggests that peak myocardial radial strain during early diastole may be superior to other Doppler imaging parameters for the noninvasive estimation of LV early diastolic function. Relationship Between Characteristics of Myocardial Radial Strain During Early Diastole and Cardiac Mechanics There was also a significant correlation between peak myocardial radial strain during early diastole and LV systolic function parameters such as the LV end-systolic volume index and LV ejection fraction. From the viewpoint of cardiac mechanics, Gilbert and Glantz28
450 Wakami et al
Journal of the American Society of Echocardiography May 2008
Figure 5 Relationships between peak myocardial radial strain during early diastole and mean pulmonary capillary wedge pressure (PCWP), left ventricular (LV) end-diastolic pressure (LVEDP), LV ejection fraction (LVEF), and LV end-systolic volume index (LVESVI). (A), Peak myocardial radial strain during early diastole decreased with increasing mean PCWP. (B), Peak myocardial radial strain during early diastole decreased with increasing LVEDP. (C), Peak myocardial radial strain during early diastole decreased with progressive impairment of LVEF. (D), Peak myocardial radial strain during early diastole decreased with increase in LVESVI. Table 2 Results of univariate and multivariate regression analyses of peak myocardial radial strain during early diastole Univariate
Multivariate
Variable
Correlation coefficient
P value
Age, y Heart rate, beats/min Mean arterial pressure, mm Hg , ms Peak negative dP/dt, mm Hg/s LV ejection fraction, % LV end-diastolic volume index, mL/m2 LV end-systolic volume index, mL/m2 LV end-diastolic pressure, mm Hg Mean pulmonary capillary wedge pressure, mm Hg
0.17 –0.20 0.065 0.80 –0.64 –0.36 0.35 0.37 0.56 0.57
.12 .061 .56 ⬍.0001 ⬍.0001 .0007 .0009 .0005 ⬍.0001 ⬍.0001
Beta coefficient
P value
0.15
.015
0.83
⬍.0001
dP/dt, First derivative of left ventricular pressure; LV, left ventricular; , time constant of left ventricular pressure decay.
reported that LVs with good systolic function have relatively smaller LV end-systolic volumes, producing a greater magnitude of LV rearrangement at early diastole through release of elastic energy stored during systole and hastening of LV relaxation. Thus, we propose that peak myocardial radial strain during early diastole reflects the mechanical nature of LV behavior over end systole to early diastole, as shown previously. Limitations Technical limitations prevented us from measuring peak myocardial radial strain during early diastole on the anterior or septal LV wall during early diastole. The right ventricle might have affected acquisi-
tion of the strain profile of the LV anterior-sided wall using the Lagrangian procedure, which requires complex calculation. Thus, we selected patients without LV motion abnormality. This may present problems for application of this method to patients with LV asynergy. Nevertheless, we believe that our findings are relevant to the noninvasive assessment of LV early diastolic function in patients without LV asynergy and that they increase the understanding of the importance of myocardial radial strain during early diastole. Conclusion The current study indicates that peak myocardial radial strain during early diastole can be used to evaluate LV early diastolic function without
Journal of the American Society of Echocardiography Volume 21 Number 5
consideration of the pseudonormalization that is observed in the transmitral flow velocity pattern with high LV filling pressure. Myocardial strain imaging in the radial direction is a promising noninvasive tool for assessing LV function in systole and early diastole. REFERENCES 1. Senni M, Tribouilloy CM, Rodeheffer RJ, Jacobsen SJ, Evans JM, Bailey KR, et al. Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation 1998;98:2282-9. 2. Kitzman DW, Little WC, Brubaker PH, Anderson RT, Hundley WG, Marburger CT, et al. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA 2002;288:2144-50. 3. Packer M. Abnormalities of diastolic function as a potential cause of exercise intolerance in chronic heart failure. Circulation 1990;81:III7886. 4. Davies SW, Fussell AL, Jordan SL, Poole-Wilson PA, Lipkin DP. Abnormal diastolic filling patterns in chronic heart failure–relationship to exercise capacity. Eur Heart J 1992;13:749-57. 5. Wheeldon NM, Clarkson P, MacDonald TM. Diastolic heart failure. Eur Heart J 1994;15:1689-97. 6. Little WC, Kitzman DW, Cheng CP. Diastolic dysfunction as a cause of exercise intolerance. Heart Fail Rev 2000;5:301-6. 7. Maruo T, Nakatani S, Jin Y, Uemura K, Sugimachi M, Ueda-Ishibashi H, et al. Evaluation of transmural distribution of viable muscle by myocardial strain profile and dobutamine stress echocardiography. Am J Physiol Heart Circ Physiol 2007;292:H921-7. 8. Armstrong G, Pasquet A, Fukamachi K, Cardon L, Olstad B, Marwick TH. Use of peak systolic strain as an index of regional left ventricular function: comparison with tissue Doppler velocity during dobutamine stress and myocardial ischemia. J Am Soc Echocardiogr 2000;13:731-7. 9. Urheim S, Edvardsen T, Torp H, Angelsen B, Smiseth OA. Myocardial strain by Doppler echocardiography: validation of a new method to quantify regional myocardial function. Circulation 2000;102:1158-64. 10. Edvardsen T, Skulstad H, Aakhus S, Urheim S, Ihlen H. Regional myocardial systolic function during acute myocardial ischemia assessed by strain Doppler echocardiography. J Am Coll Cardiol 2001;37:726-30. 11. Abraham TP, Nishimura RA. Myocardial strain: can we finally measure contractility? J Am Coll Cardiol 2001;37:731-4. 12. Koyama J, Ray-Sequin PA, Falk RH. Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis. Circulation 2003;107:2446-52. 13. Leitman M, Lysyansky P, Sidenko S, Shir V, Peleg E, Binenbaum M, et al. Two-dimensional strain–a novel software for real-time quantitative echocardiographic assessment of myocardial function. J Am Soc Echocardiogr 2004;17:1021-9.
Wakami et al
451
14. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997;30:1527-33. 15. Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 2000;102:1788-94. 16. Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 2003;289:194-202. 17. D’hooge J, Heimdal A, Jamal F, Kukulski T, Bijnens B, Rademakers F, et al. Regional strain and strain rate measurements by cardiac ultrasound: principles, implementation and limitations. Eur J Echocardiogr 2000;1: 154-70. 18. Weiss JL, Frederiksen JW, Weisfeldt ML. Hemodynamic determinants of the time-course of fall in canine left ventricular pressure. J Clin Invest 1976;58:751-60. 19. Chapman CB, Baker O, Reynolds J, Bonte FJ. Use of biplane cinefluorography for measurement of ventricular volume. Circulation 1958;18: 1105-17. 20. Sheehan FH, Bolson EL, Dodge HT, Mathey DG, Schofer J, Woo HW. Advantages and applications of centerline method for characterizing regional ventricular function. Circulation 1986;74:293-305. 21. Yoshida T, Ohte N, Narita H, Sakata S, Wakami K, Asada K, et al. Lack of inertia force of late systolic aortic flow is a cause of left ventricular isolated diastolic dysfunction in patients with coronary artery disease. J Am Coll Cardiol 2006;48:983-91. 22. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307-10. 23. Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 1997;30:474-80. 24. Oki T, Tabata T, Yamada H, Wakatsuki T, Shinohara H, Nishikado A, et al. Clinical application of pulsed Doppler tissue imaging for assessing abnormal left ventricular relaxation. Am J Cardiol 1997;79:921-8. 25. Ohte N, Narita H, Hashimoto T, Akita S, Kurokawa K, Fujinami T. Evaluation of left ventricular early diastolic performance by color tissue Doppler imaging of the mitral annulus. Am J Cardiol 1998;82:1414-7. 26. Nagueh SF, Sun H, Kopelen HA, Middleton KJ, Khoury DS. Hemodynamic determinants of the mitral annulus diastolic velocities by tissue Doppler. J Am Coll Cardiol 2001;37:278-85. 27. Vinereanu D, Nicolaides E, Tweddel AC, Mädler CF, Holst B, Boden LE, et al. Subclinical left ventricular dysfunction in asymptomatic patients with type 2 diabetes mellitus, related to serum lipids and glycated hemoglobin. Clin Sci (Colch) 2003;105;591-9. 28. Gilbert JC, Glantz SA. Determinants of left ventricular filling and of the diastolic pressure-volume relation. Circ Res 1989;64:827-52.