Peak Early Diastolic Mitral Annulus Velocity by Tissue Doppler Imaging Adds Independent and Incremental Prognostic Value

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1 Journal of the American College of Cardiology Vol. 41, No. 5, by the American College of Cardiology Foundation ISSN /03/$30.00 Published by Elsevier Science Inc. doi: /s (02) Peak Early Diastolic Mitral Annulus Velocity by Tissue Doppler Imaging Adds Independent and Incremental Prognostic Value Mei Wang, MD,* Gabriel W. K. Yip, MRCP,* Angela Y. M. Wang, MB,* Yan Zhang, MD,* Pik Yuk Ho, BN,* Mui Kiu Tse, RN,* Peggo K. W. Lam, MA, John E. Sanderson, MD, FRCP, FACC* Hong Kong SAR, China OBJECTIVES BACKGROUND METHODS RESULTS CONCLUSIONS The aim of this study was to ascertain if left ventricular mitral annulus velocities measured by tissue Doppler imaging (TDI) are more powerful predictors of outcome compared with clinical data and standard Doppler-echocardiographic parameters. Tissue Doppler imaging of basal or mitral annulus velocities provides rapid assessment of ventricular long axis function. But it is not known if TDI-derived velocities in systole and diastole add incremental value and are superior to the standard Doppler-echocardiographic measurements as a predictor of outcome. The study population consisted of 518 subjects, 353 with cardiac disease and 165 normal subjects who had full Doppler two-dimensional echocardiographic studies with measurement of mitral inflow velocities in early and late diastole, E-wave deceleration time (DT), peak systolic mitral annular velocity (Sm) early and late diastolic mitral annular velocity (Em and Am) by TDI, early diastolic flow propagation velocity, and standard chamber dimensions. All subjects were followed up for two years. The end point was cardiac death. Tissue Doppler imaging mitral annulus systolic and diastolic velocities were all significantly lower in the non-survivors (all p 0.05) as was DT (p 0.024). In the Cox model the best predictors of mortality were Em, Sm, Am, left ventricular ejection fraction, left ventricular mass, and left atrial diameter in systole (LADs). By backward stepwise analysis Em and LADs were the strongest predictors. After forcing the TDI measurements into the covariate model with clinical and mitral DT 0.16 s, Em provided significant incremental value for predicting cardiac mortality (p 0.004). Mitral annulus velocity measured by TDI in early diastole gives incremental predictive power for cardiac mortality compared to clinical data and standard echocardiographic measurements. This easily available measurement adds significant value in the clinical management of cardiac patients. (J Am Coll Cardiol 2003;41:820 6) 2003 by the American College of Cardiology Foundation A variety of indices derived from Doppler-echocardiography have been used to predict outcome in patients with left ventricular (LV) dysfunction including LV cavity dimensions, ejection fraction, and mitral inflow velocities. Shortening of the early diastolic deceleration time (DT) of the mitral E-wave suggests impaired LV filling and increased left atrial (LA) pressure and it has been shown to be a strong predictor of an adverse outcome in symptomatic and asymptomatic individuals with LV dysfunction (1 3). However, the confounding effects of changes in loading conditions can significantly affect the measurements based on Doppler recordings of ventricular filling velocities. Recently, tissue Doppler imaging (TDI) which measures the velocity of the myocardium during the cardiac cycle has been used to assess systolic and diastolic function (4). Tissue Doppler imaging can be used to measure mitral or tricuspid annulus velocities that reflect ventricular function in the long axis (5,6). Several studies have shown that the early mitral annulus velocity is a relatively preload-independent assessment of From the *Division of Cardiology, Department of Medicine and Therapeutics and the Center of Clinical Trials and Epidemiological Research, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China. Manuscript received May 22, 2002; revised manuscript received July 26, 2002, accepted August 1, LV relaxation (7,8), and the ratio of peak early diastolic mitral inflow velocity (E) over the myocardial velocity can be used to estimate LV filling pressure (8 10). However, these measurements based on myocardial velocities have not been compared directly with other standard Dopplerechocardiographic measurements, including DT, for predicting prognosis. Thus, the purpose of this study was to examine whether TDI derived parameters added incremental value to clinical and other standard Dopplerechocardiographic measurements to predict cardiac mortality in patients with a variety of cardiac diseases and ventricular function. METHODS Subjects. The study population consisted of 518 subjects (243 females and 275 males), mean age 57.5 years (range 19 to 90 years) who were referred to the Echocardiographic Laboratory at the Prince of Wales Hospital during 1999 to Patients with a variety of cardiac diseases and ventricular function were prospectively recruited as well a group of entirely normal subjects (n 165) without any objective evidence of cardiac or other diseases were studied.

2 JACC Vol. 41, No. 5, 2003 March 5, 2003:820 6 Wang et al. TDI Predicts Prognosis 821 Abbreviations and Acronyms Am late diastolic mitral annular velocity CI confidence interval DT mitral deceleration time E early diastolic mitral inflow velocity Em early diastolic mitral annular velocity HR hazard ratio LA left atrial LADs left atrial diameter in systole LV left ventricular LVEF left ventricular ejection fraction Sm systolic mitral annular velocity TDI tissue Doppler imaging Vp left ventricular flow propagation velocity Echocardiography. Echocardiograms were obtained using commercially available ultrasound equipment (GE- VingMed System FiVe with a 3.5 MHz transducer, General Electric-VingMed Sound AB, Horten, Norway). All patients were examined at rest in the left lateral decubitus position. All recordings were performed by one investigator (M. W.). The echocardiographic techniques and calculations of different cardiac dimension and volumes were performed according to the recommendations of the American Society of Echocardiography (11,12). Left ventricular ejection fraction (LVEF) by two-dimensional echocardiography was obtained by modified biplane Simpson s method from apical four- and two-chamber views. M-mode measurements. Left ventricular dimensions and wall thickness were made in parasternal long axis with M-mode cursor positioned just beyond the mitral leaflet tips, perpendicular to the long axis of the ventricle. Left ventricular diameter in diastole and systole, LV mass, and fracture shortening were measured. Left atrial dimension at the end of systole (LADs) was assessed by M-mode cursor through the aortic valve in parasternal long-axis view. Mitral flow velocities. The mitral flow velocities were recorded with pulsed wave Doppler with the sample volume placed at the tip of the mitral valve tips from the apical four-chamber view. From the mitral valve inflow velocity curve the following measurements were made: peak E-wave velocity and its DT, peak A-wave velocity, and the isovolumic relaxation time was measured from aortic valve closure to the mitral valve opening. TDI. Myocardial velocities were recorded using a standard pulse-wave Doppler technique as previously described (8,9,13). Color-coded tissue Doppler images were acquired over a predetermined two consecutive cardiac cycles for each of four mitral annular segments and were transferred to a workstation composed of a personal computer whose software package provides customized image visualization, processing, and analysis (Echopac, GE-VingMed, Norway). The sample volume was placed at the junction of the LV wall with the mitral annulus of the septal and lateral myocardial segments from the four-chamber view and inferior and anterior myocardial segments from the twochamber view. Peak velocities during systole (Sm), early diastole (Em), and late diastole (Am) were measured. The final value represented the average of four sites. Propagation velocity. Color M-mode Doppler propagation velocities of LV flow in early diastole was obtained from the apical four-chamber view. An M-mode cursor was placed as parallel as possible through the center of the mitral inflow, and position was adjusted to obtain the longest column of color flow from the mitral annulus to apex. Velocities were acquired by a rainbow color system, which was adjusted using pulse repetition frequency. Propagation velocity was measured by the slope along the bright yellow (aliasing) isovelocity line during early filling, from the mitral valve plane to 4 cm distally into the LV cavity as previously recommended (14). Outcome measurements. All patients were prospectively followed for two years. Death and mode of death were identified from hospital records or telephone contact with relatives. Cardiac death was defined as death caused by heart disease including sudden death. Ischemic heart disease and heart failure were the most common cause. Statistics analysis. Continuous data are expressed as mean and 95% confidence interval (CI). Comparison between groups of continuous variables were tested by unpaired t test. Each variable was evaluated by using Cox proportional hazard survival analysis for cardiac death. The univariate variables that had significant difference with the occurrence of a cardiac death were identified. Multivariate analysis of the univariate variables was then performed and adjusted for age and LV/LA geometry to identify independent predictors of cardiac death with each model (p 0.05). Each model was the variables identified to have significant relationship to cardiac mortality interpreted by age and LV/LA geometry. Patients who died from other causes of death or lost to follow-up were censored. The incremental value of TDI over clinical data and mitral inflow variables was assessed by a modified stepwise procedure in three modeling steps in the same order as in clinical practice. The first step consisted of fitting a multivariate model of clinical data used as baseline risk factors. Then mitral inflow variables were added in a stepwise backward selection manner to the clinical model. The third step consisted of adding TDI variables to the second model. A significant improvement in model prediction was based on the likelihood ratio statistic, which follows a chi-square distribution and the p value was based on the incremental value compared to the previous model. Cumulative survival curves were performed by Kaplan- Meier method. Subgroups of life-table curves were compared using Cox regression model. A value of p 0.05 was considered significant. RESULTS The study population was followed-up for a mean of 23 months (range 0.3 to 36 months). Forty-six patients

3 822 Wang et al. JACC Vol. 41, No. 5, 2003 TDI Predicts Prognosis March 5, 2003:820 6 Table 1. Clinical Features and Cardiac Mortality: Relationship Between Etiologic Diagnosis at Baseline and Cardiac Deaths Total Numbers (%) Cardiac Deaths Percentage Cardiac Mortality Normal subjects 165 (31.9) 0 0 Hypertension 179 (34.6) Ischemic heart disease 85 (16.4) Valvular heart disease 50 (9.7) Heart failure 96 (18.5) Diabetes mellitus 87 (16.8) Obstructive sleep apnea 24 (4.6) (8.88%) died and 33 patients (6.37%) died due to a cardiac cause (1 subject was lost to follow-up). Causes of cardiac death were an ischemic event (acute coronary syndrome with or without myocardial infarction), heart failure, or sudden death. Thirteen patients died due to other causes: 4 died from severe peritonitis associated with peritoneal dialysis, 2 from cerebral vascular accidents, 2 from cancer, 1 from pneumonia, 1 from postoperative complications (noncardiac), and 3 deaths were unknown. Standard clinical and echocardiographic measurements and outcome. The relationship between etiology and subsequent mortality rates are shown in Table 1. The association between the clinical and echocardiographic variables and the end point was assessed by univariate analysis as shown in Table 2. Hazard ratios for these variables are also shown. The differences in echocardiographic parameters between those alive or dead are shown in Table 3. There was a significant difference in age and LV/LA geometry between the survivors and non-survivors except for LV diameter in systole. After all geometric variables were entered into Cox regression analysis, LADs was the only geometric variable predicting the cardiac mortality rather than LV diameter in diastole and systole (hazard ratio [HR]: 2.96, 95% CI: 1.13 to 7.78). There was also a significant difference in LVEF by two-dimensional echocardiography and fractional shortening between those alive and cardiac deaths as shown in Table 3. After each of these significant variables was entered into Cox regression model interacted by age and LV/LA geometry, LVEF remained associated with cardiac deaths (HR: 0.84, 95% CI: 0.73 to 0.97). Left ventricular mass was significantly lower in the survivors compared to those who died ( vs , p ). Univariate analysis showed that LV mass was significantly associated with cardiac death (HR: 1.004, 95% CI: to 1.006). After LV mass was entered into Cox regression model interacted by age and LV/LA geometry, it was still strongly related to cardiac mortality (HR: 1.005, 95% CI: to 1.009). After the clinical features were adjusted by stepwise backward manner in the multivariate analysis, significant clinical risk factors for cardiac death were ischemic heart disease, diabetes, heart failure, and chronic renal failure (p 0.05) (Table 4). Table 2. Univariate Predictors of Cardiac Deaths HR (95% CI) Clinical Age ( ) Gender Heart rate ( ) Hypertension ( ) Ischemic heart disease ( ) Valvular heart disease ( ) Heart failure ( ) Diabetes mellitus ( ) Chronic renal failure ( ) Echocardiography LVEF 45% ( ) Fractional shortening 25% ( ) LV mass ( ) LV end-diastolic diameter ( ) LV end-systolic diameter LADs ( ) Mitral inflow E ( ) A DT 0.16 s ( ) IVRT TDI Sm 3 cm/s ( ) Em 3 cm/s ( ) Am 4 cm/s ( ) LV filling pressure E/Em ( ) E/Vp ( ) A late diastolic mitral inflow velocity; Am late diastolic mitral annular velocity; CI confidence interval; DT deceleration time; E early diastolic mitral inflow velocity; Em early diastolic mitral annular velocity; HR hazard ratio; IVRT isovolumic relaxation time of mitral inflow; LADs left atrial diameter in systole; LV left ventricular; LVEF2D left ventricular ejection fraction by twodimensional echocardiography; Sm systolic mitral annular velocity; TDI tissue Doppler imaging; Vp left ventricular flow propagation velocity. Doppler mitral inflow parameters. Early diastolic mitral inflow velocity and DT 0.16 s were associated with cardiac death by using univariate Cox regression analysis (Table 2). In the multivariate analysis DT 0.16 s (HR: 2.43, 95% CI: 1.13 to 5.24) was the most important predictor of cardiac death compared to other Doppler mitral inflow parameters. The DT 0.16 s also improved predictive cardiac mortality compared to clinical data (p 0.025) as shown in Figure 1. TDI parameters. There was significant difference between the survivors and non-surviors for Sm, Em, and Am (Table 3). There was no difference in E/Am. Univariate associations with cardiac mortality was shown in Table 2. The Sm, Em, Am remained significant amongst clinical data and DT 0.16 s after adjustment for age and LV/LA geometry in the Cox regression analysis. Using the stepwise incremental model, TDI variables provided incremental value for risk stratification, additional to clinical data and DT 0.16 s as indicated by the increase of the chi-square of the incremental model by the use of TDI echocardiographic data (p 0.008) in Figure 1. However, in the multivariate (backward stepwise) analysis Em had a strongest impact on cardiac mortality amongst TDI variables as shown in Table 4. The parameters of E/Em and E/left ventricular flow

4 JACC Vol. 41, No. 5, 2003 March 5, 2003:820 6 Wang et al. TDI Predicts Prognosis 823 Table 3. Doppler-Echocardiographic parameters [Mean (95% CI)] and Survival Normals Patients Survivors Non-Survivors Age 50 ( ) 61 ( ) 57 ( ) 65 ( ) LVEDD, cm 4.6 ( ) 5.3 ( ) 5.0 ( ) 5.4 ( ) LVESD, cm 2.9 ( ) 3.8 ( ) 3.6 ( ) 4.1 ( ) LADs, cm 3.4 ( ) 4.2 ( ) 4.0 ( ) 4.7 ( )* LV mass, g 191 ( ) 351 ( ) 293 ( ) 392 ( )* LVEF2D, % 62 (61 64) 48 (47 50) 53 (52 55) 40 (36 45)* FS, % 36 (35 37) 28 (27 29) 31 (30 32) 23 (20 27)* TDI Sm, cm/s 6.4 ( ) 4.5 ( ) 5.2 ( ) 3.2 ( )* Em, cm/s 8.1 ( ) 4.5 ( ) 5.8 ( ) 3.2 ( )* Am, cm/s 7.3 ( ) 6.3 ( ) 6.8 ( ) 4.8 ( )* E/Am 1.2 ( ) 0.9 ( ) 1.0 ( ) 0.9 ( ) Mitral inflow variables E, m/s 0.77 ( ) 0.75 ( ) 0.75 ( ) 0.85 ( ) A, m/s 0.67 ( ) 0.79 ( ) 0.75 ( ) 0.75 ( ) DT, s 0.18 ( ) 0.21 ( ) 0.20 ( ) 0.18 ( ) IVRT, s 0.10 ( ) 0.10 ( ) 0.10 ( ) 0.10 ( ) E/A 1.2 ( ) 1.1 ( ) 1.1 ( ) 1.3 ( ) Propagation velocity, cm/s 55 (52 58) 42 (40 44) 44 (43 46) 43 (35 50) E/Em 10 (9 10) 20 (19 22) 16 (15 17) 30 (24 36)* E/Vp 1.5 ( ) 2.0 ( ) 1.9 ( ) 2.2 ( ) *Survivors vs. Non-survivors p ; Survivors vs. Non-survivors p LVEDD left ventricular end-diastolic diameter; LVESD left ventricular end-systolic diameter; FS left ventricular fractional shortening; other abbreviations as in Table 2. propagation velocity (Vp) (both indirect measures of LV filling pressures) were also associated with cardiac mortality. After both measurements were entered into the covariate model with clinical data and DT 0.16 s, E/Em (HR: 1.02, 95% CI: to 1.052) was a stronger predictor compared to E/Vp but it did not provide incremental value to clinical and DT 0.16 s (p 0.13). Survival curve. Cardiac mortality was compared by Kaplan-Meier analysis according to tertiles of Em or Sm: 3,3to5,and 5 cm/s (Figs. 2 and 3). When Em or Sm was 3 but 5 cm/s, the HR of cardiac death was significantly increased compared with Em or Sm 5 cm/s (HR of Em: 12.79, 95% CI: 2.92 to 56.01; HR of Sm: 5.73, 95% CI: 1.87 to 17.60) Furthermore, when Em or Sm was 3 cm/s, the HR of cardiac death was significantly increased compared with Em or Sm 5 cm/s (HR of Em: 28.47, 95% CI: 6.50 to ; HR of Sm: 20.55, 95% CI: 6.86 to 61.62). Similarly, cardiac deaths were compared by Kaplan- Meier analysis according to tertiles of Am: 4,4to7,and 7 cm/s. When Am was 4 but 7 cm/s, the HR of cardiac death was increased compared with Am 7 cm/s (HR: 4.28, 95% CI: 1.54 to 11.87). When Am was 4 cm/s, the HR of cardiac death was significantly increased compared with Am 7 cm/s (HR: 11.53, 95% CI: 4.10 to 32.39). The E/Em was also analyzed with respect to cardiac deaths according to tertiles: 15, 15 to 20, and 20. When E/Em was 15 but 20, the HR of cardiac death was increased but not statistically significantly compared with E/Em 15 (HR: 4.75, 95% CI: 0.96 to 23.58). When E/Em was 20, the HR of cardiac death was significantly increased compared with E/Em 15 (HR: 20.00, 95% CI: 5.95 to 67.23). Table 4. Multivariate Analysis (Backward Stepwise) Predictors of Cardiac Mortality HR (95% CI) Ischemic heart disease ( ) Diabetes mellitus ( ) Heart failure ( ) Chronic renal failure ( ) DT 0.16 s ( ) Em, cm/s ( ) CI confidence interval; DT deceleration time; Em early diastolic mitral annular velocity; HR hazard ratio. Figure 1. Incremental value of deceleration time (DT) 0.16 s and tissue Doppler imaging (TDI) parameters in predicting cardiac death. White bar clinical data; shaded bar clinical data DT 0.16 s; black bar clinical data DT 0.16 s TDI variables (Sm, Em, Am).

5 824 Wang et al. JACC Vol. 41, No. 5, 2003 TDI Predicts Prognosis March 5, 2003:820 6 Figure 2. Cumulative cardiac death by tertiles of the early mitral annulus diastolic velocity (Em). DISCUSSION In this study in patients with a variety of cardiac diseases TDI parameters, especially Em, were the most powerful predictors of cardiac death in the subsequent two years, and provide significant incremental prognostic value compared with clinical information and variables derived from mitral inflow velocities such as a mitral E-wave DT 160 ms. Although the ratio E/Em did not give incremental prognostic value, it was another powerful predictor of cardiac death. Those patients with an Em 3 cm/s, Sm 3 cm/s, Am 4 cm/s, and E/Em 20 were at most at risk of cardiac death in the following two years. TDI variables and prognosis. Several studies that have assessed the prognostic significance of echocardiographic derived measurements, such as LVEF (15,16), LADs (17), LV mass (18), systolic and diastolic time intervals (19), and particularly those derived from Doppler studies of mitral inflow velocities such as DT (1 3). Studies that have used TDI, however, are limited. Our results show for the first time the value of Em for determining cardiac mortality in a large number of subjects with a variety of cardiac vascular etiologies. The final mechanism in these different diseases is probably the same, that is, ischemia of subendocardial fibers. Tissue Doppler imaging enables regional and global myocardial systolic and diastolic velocities to be measured. The velocities derived from the annulus or LV base primarily reflect longitudinal motion, due to the longitudinally directed fibers, which are found in the subendocardium (5,20). This may explain why these measurements are so useful for the assessment of the consequences of ischemia, to which the subendocardium is particularly sensitive (20 22). When the annulus/basal velocity is averaged from four sites septal, lateral, inferior, and anterior it reflects global function. The Sm has been shown to be a good measurement of global systolic function (6) and can detect abnormal systolic function in patients with heart failure and a normal ejection fraction (diastolic heart failure) (23). The Em appears to be a good indicator of diastolic function and correlates well with the time constant of isovolumic relaxation (Tau) (6,24,25). Nagueh et al. (26) also demonstrated that load increases on average raised the transmitral E velocity by 70%, whereas the same manipulations produced only a 13% change in Em. Therefore, low Em values are indicative of abnormal LV relaxation even when LV filling pressures are increased. However, age does affect TDI variables especially Em (27). Our results show that TDI parameters were still associated with cardiac mortality even after adjusting for age-related changes based on a large number of normal subjects. Therefore, both Sm and Em appear to be good independent indices of systolic and diastolic function respectively, and although Em is marginally superior as a prognosticator they are intrinsically linked as systolic func-

6 JACC Vol. 41, No. 5, 2003 March 5, 2003:820 6 Wang et al. TDI Predicts Prognosis 825 Figure 3. Cumulative cardiac death by tertiles of the mitral annulus systolic velocity (Sm). tion determines to some extent LV relaxation in early diastole (27). LV filling pressure and prognosis. Recently, E/Vp and E/Em have been reported to be good noninvasive correlates of pulmonary capillary wedge pressure (28) and LV filling pressure (8 10). Moller et al. (29) found them to be powerful predictors of the composite end point of cardiac death and readmission due to heart failure after a first myocardial infarction during a median follow-up of 13 months. By contrast, in our study we found that E/Em was a more powerful predictor of future cardiac mortality than E/Vp. The difference between our study and the one by Moller et al. (29) may be that in their study they used a composite end point which included heart failure readmissions increasing bias towards those with an already high filling pressure. Study limitations. Our results showed that heart rate also correlated with cardiac death in the univariate analysis, but it was excluded in the multivariate stepwise analysis. Some studies have shown that tachycardia may increase the late mitral inflow velocity, but it does not appear to influence the early DT (28,29). Secondly, LVEF was another important predictor related to outcome. But it was interacted by DT and was not included in the multivariate analysis. The main aim of the study was to determine if TDI parameters provide incremental value compared with mitral diastolic velocities and DT, which are commonly used. Thirdly, our study end point was cardiac mortality including sudden death. Sudden death is contentious and although it is assumed this is due to a cardiac arrhythmia this cannot be proved. Not all these patients had an autopsy to exclude other possibilities, such as pulmonary embolism or cerebral hemorrhage, although it is unlikely these would constitute more than a fraction of cases. CONCLUSIONS The TDI derived parameters Sm, Em, and Am are powerful predictors of cardiac mortality. An Em 3 cm/s, Sm 3 cm/s, Am 4 cm/s, and E/Em 20 can identify patients at very high risk of cardiac death in the subsequent two years. Reprint requests and correspondence: Dr. John E. Sanderson, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Clinical Sciences Building, Prince of Wales Hospital, Shatin, N. T., Hong Kong SAR, China. jesanderson@cuhk.edu.hk. REFERENCES 1. Giannuzzi P, Temporelli PL, Bosimini E, et al. Independent and incremental prognostic value of Doppler-derived mitral deceleration time of early filling in both symptomatic and asymptomatic patients with left ventricular dysfunction. J Am Coll Cardiol 1996;28: Xie GY, Berk MR, Smith MD, et al. Prognostic value of Doppler transmitral flow patterns in patients with congestive heart failure. J Am Coll Cardiol 1994;24:132 9.

7 826 Wang et al. JACC Vol. 41, No. 5, 2003 TDI Predicts Prognosis March 5, 2003: Oh JK, Ding ZP, Gersh BJ, et al. Restrictive left ventricular diastolic filling identifies patients with heart failure after acute myocardial infarction. J Am Soc Echocardiogr 1992;5: Sutherland GR, Steward MJ, Grounstroem KWE, et al. Color Doppler myocardial imaging: a new technique for the assessment of myocardial function. J Am Soc Echocardiogr 1994;7: Henein MY, Gibson DG. Long axis function in disease. Heart 1999;81: Gulati V, Katz WE, Follansbee WP, Gorscan J III. Mitral annular descent velocity by tissue Doppler echocardiography as index of global left ventricular function. Am J Cardiol 1996;77: Sohn DW, Chai IH, Lee DJ, 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: Oki T, Tabata T, Yamada H, et al. Clinical application of pulsed Doppler tissue imaging for assessing abnormal left ventricular relaxation. Am J Cardiol 1997;79: Nagueh SF, Middleton KJ, Kopelen HA, et al. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997;30: Nagueh SF, Mikati I, Koplen HA, et al. Doppler estimation of left ventricular filling pressure in sinus tachycardia: a new application of tissue Doppler imaging. Circulation 1998;98: Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricular by two-dimensional echocardiography. American Society of Echocardiography committee on standards, subcommittee on quantitation of two-dimensional echocardiograms. J Am Soc Echocardiogr 1989;2: Schiller NB. Two-dimensional echocardiographic determination of left ventricular volume, systolic function, and mass. Summary and discussion of the 1989 recommendations of the American Society of Echocardiography. Circulation 1991;84: Nagueh SF, Lakkis NM, Middleton KJ, et al. Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy. Circulation 1999;99: Garcia MJ, Palac RT, Malenka DJ, et al. Color M-mode Doppler flow propagation velocity is a relatively preload-independent index of left ventricular filling. J Am Soc Echocardiogr 1999;12: Nelson GR, Cohn PF, Gorlin R. Prognosis in medically treated coronary artery disease. Influence of ejection fraction compared to other parameters. Circulation 1975;52: Kelly MJ, Thompson PL, Quinlan MF. Prognostic significance of left ventricular ejection fraction after acute myocardial infarction. A bedside radio nuclide study. Br Heart J 1985;53: Eriksson SV, Caidahl K, Hamsten A, et al. Long-term prognostic significance of M-mode echocardiography in young men after myocardial infarction. Br Heart J 1995;74: Schillaci G, Verdecchia P, Porcellati C, et al. Continuous relation between left ventricular mass and cardiovascular risk in essential hypertension. Hypertension 2000;35: Dujardin KS, Tei CW, Yeo TC, et al. Prognostic value of a Doppler index combining systolic and diastolic performance in idiopathic dilated cardiomyopathy. Am J Cardiol 1998;82: Simpson IA. Echocardiographic assessment of the long axis: a simple solution to a complex problem. Heart 1997;78: Alam M, Hogherd C, Thorstrand C, et al. Haemodynamic significance of the atrioventricular plane displacement in patients with coronary artery disease. Eur Heart J 1992;13: Henein MY, Priestley K, Davarashvili T, et al. Early changes in left ventricular subendocardial function after successful coronary angioplasty. Br Heart J 1993;69: Yip G, Wang M, Zhang Y, Sanderson JE. Left ventricular long axis function in diastolic heart failure is reduced in both diastole and systole: time for a redefinition? Heart 2002;87: Ohte N, Narita H, Hashimoto T, et al. Differentiation of abnormal relaxation pattern with aging from abnormal relaxation pattern with coronary artery disease in transmitral flow with the use of tissue Doppler imaging of the mitral annulus. J Am Soc Echocardiogr 1999;12: Oki T, Tabata T, Yamada H, et al. Left ventricular diastolic properties of hypertensive patients measured by pulsed tissue Doppler imaging. J Am Soc Echocardiogr 1998;11: Nagueh SF, Sun HB, Kopelen HA, et al. Hemodynamic determinants of the mitral annulus diastolic velocities by tissue Doppler. J Am Coll Cardiol 2001;37: Yip GW, Zhang Y, Tan PY, et al. Left ventricular long-axis changes in early diastole and systole: impact of systolic function on diastole. Clin Sci (Lond) 2002;102: Garcia MJ, Ares MA, Asher C, et al. An index of early left ventricular filling that combined with pulsed Doppler peak E velocity may estimate capillary wedge pressure. J Am Coll Cardiol 1997;29: Moller JE, Sondergaard E, Poulsen SH, et al. Color M-mode and pulsed wave tissue Doppler echocardiography: powerful predictors of cardiac events after first myocardial infarction. J Am Soc Echocardiogr 2001;14: