Usefulness of Ventricular Longitudinal Contractility Assessed by Doppler Tissue Imaging in the Prediction of Reverse Remodeling in Patients with Severe Left Ventricular Systolic Dysfunction

Usefulness of Ventricular Longitudinal Contractility Assessed by Doppler Tissue Imaging in the Prediction of Reverse Remodeling in Patients with Severe Left Ventricular Systolic Dysfunction Soo-Jin Kang, MD, Jae-Kwan Song, MD, PhD, Jong-Min Song, MD, Duk-Hyun Kang, MD, Eun Young Lee, RDCS, Jun Kim, MD, Gi-Byoung Nam, MD, Kee-Joon Choi, MD, Jae-Joong Kim, MD, and You-Ho Kim, MD, Seoul, South Korea

Objective: We sought to test if assessment of ventricular longitudinal contractility (LC) by Doppler tissue imaging (DTI) can predict reverse remodeling (RR) of left ventricular (LV) dysfunction resulting from medical treatment. Methods: DTI was performed in 35 patients with nonischemic LV dysfunction (ejection fraction 26 ⴞ 7%) and LC was assessed at the 4 different basal segments of the LV walls (septal, lateral, inferior, and anterior) using myocardial velocity curves and strain measurements; the peak systolic or delayed longitudinal contraction velocity of LV walls only with concomitant negative strain were measured and added to represent LC of each patient (LC by DTI). Successful RR was defined as a reduction of LV end-systolic volume of greater than 15%. Results: RR was observed in 13 patients (37%, group A). Initial LV ejection fraction was similar in patients

Although myocardial failure is generally consid-

ered an irreversible and progressive process characterized by left ventricular (LV) remodeling, some patients with marked LV dysfunction have been reported to show functional improvement or reverse remodeling (RR) after aggressive medical treatment,1-4 leading many investigators to seek predictors of RR.5-8 Echocardiographic indexes of ventricular systolic and diastolic function have become indispensable in evaluating patients with LV dysfunction, and have been tested as prognostic markers.9-13 The recently introduced Doppler tissue imaging (DTI) technique proFrom the Division of Cardiology, Asan Medical Center, University of Ulsan, College of Medicine. Reprint requests: Jae-Kwan Song, MD, PhD, Asan Medical Center, University of Ulsan, College of Medicine, 388-1 Poongnapdong Songpa-ku, Seoul 138-736, South Korea (E-mail: jksong@ amc.seoul.kr). 0894-7317/$32.00 Copyright 2006 by the American Society of Echocardiography. doi:10.1016/j.echo.2005.08.009

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who did and did not achieve RR (group B). Compared with group B, group A showed shorter QRS interval (110 ⴞ 36 vs 136 ⴞ 28 milliseconds, P ⴝ .022), shorter symptom duration (2.3 ⴞ 3.5 vs 4.2 ⴞ 3.4 years, P ⴝ .047), lower prevalence of left bundle branch block (23% vs 59%, P ⴝ .039), and higher value of LC by DTI (9.6 ⴞ 3.5 vs 6.3 ⴞ 3.6 cm/s, P ⴝ .011). Multivariate analysis revealed that symptom duration less than 2 years (odds ratio ⴝ 8.0, 95% confidence interval ⴝ 1.3-47.2, P ⴝ .022) and LC by DTI (odds ratio ⴝ 1.3, 95% confidence interval ⴝ 1.0-1.7, P ⴝ .019) were independent predictors of RR. Conclusions: DTI provides a new index of LC, which is useful for predicting RR in patients with severe LV dysfunction. (J Am Soc Echocardiogr 2006;19: 178-184.)

vides unique information regarding regional myocardial function and ventricular longitudinal contractility (LC).14 Although it is well known that DTI is useful in assessing mechanical dyssynchrony in patients with LV dysfunction receiving cardiac resynchronization therapy,15-21 the prognostic implication of LC assessment has not been tested. We hypothesized that the remaining LC represents myocardial contractile reserve of biologic function, which is critical or prerequisite for RR resulting from medical treatment. The aim of this study was to test whether LC, assessed by DTI, can predict RR of LV dysfunction.

METHODS Subjects From September 2002 to October 2003, 35 patients with nonischemic dilated cardiomyopathy, who underwent both

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Figure 1 Classification of myocardial velocity curves using velocity data from Doppler tissue imaging (top) and strain measurements (bottom). baseline and follow-up echocardiography, were enrolled; their LV ejection fraction (EF) was less than 35% and these patients were specifically referred to our heart failure department for special care and potential consideration of heart transplantation. Diagnostic coronary angiography was performed to rule out ischemic cardiomyopathy and patients with atrial fibrillation were excluded. All patients received medical treatment after discharge and regular follow-up through a special outpatient clinic of the heart failure department was done. The mean age of the patients was 57 ⫾ 16 years and there were 21 men (60%). All patients underwent comprehensive echocardiography at baseline, including DTI. The LV volumes and EF were calculated by biplane Simpson’s equation using the apical 4and 2-chamber views. LV spherical index was defined as the ratio of the long-axis dimension from the LV apex to the center of the mitral annular plane to the short-axis diameter calculated at the apical 4-chamber view. LC was assessed by color DTI of the LV at the apical 4- and 2-chamber view (Vivid 7, GE-Vingmed, Horten, Norway). Three consecutive beats at each view were stored for online analysis. In patients with markedly dilated and distorted LV, the transducer position was modified to put the LV walls as parallel as possible to the central ultrasound beam, especially for the lateral and anterior wall; the angle between the Doppler beam and the wall was kept at less than 30 degrees. All patients were treated and followed up by a dedicated specialist (J-J. K.) of the heart failure department, and all

received a flexible regimen of diuretics and angiotensinconverting enzyme inhibitors, which were replaced by angiotensin type I receptor blockers if these were not tolerated. Digitalis was prescribed in all cases, and carvedilol was used under rigorous supervision. Spironolactone was added for patients with functional class III or more with medications mentioned above. The compliance of the patients was monitored by a trained clinical nurse specialist. Regular clinical and echocardiographic evaluation was recommended; if several echocardiographic studies were performed during follow-up, the last one (13.4 ⫾ 6.2 months after discharge) was considered representative. Successful RR was defined as a reduction of LV end-systolic volume of greater than 15%,21 and baseline clinical characteristics were compared between patients who did and did not attain RR. Analysis of DTI Pulsed Doppler velocity profile signals were reconstituted from color DTI to obtain myocardial velocity curves of the LV walls (Figure 1). Myocardial velocity curves were obtained at the 4 basal segments of the LV walls (septal, lateral, inferior, and anterior). The peak systolic or delayed longitudinal contraction velocity was measured, and the strain curve of each LV wall was obtained using the same sample area with the length of 12 mm (Figure 1). To minimize the potential errors related to inherent noise of strain curve measured by DTI, only strain curves that came to the

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Figure 2 Representative myocardial velocity profiles (A and C) with strain measurements (B and D) for patient with left ventricular (LV) systolic dysfunction who achieved successful reverse remodeling. Peak systolic velocity of septal (yellow) (A), lateral (green) (A), and inferior (yellow) (B) walls was higher than 2.0 cm/s, with concomitant negative strain, compatible with type I pattern. In contrast, anterior wall (green) (B) showed prominent delayed contraction wave with negative strain, compatible with type II pattern. Thus, calculated longitudinal contractility index by Doppler tissue imaging was 16.2 (5.2 ⫹ 3.2 ⫹ 2.9 ⫹ 4.9) cm/s and SD of time to peak systolic velocity of 8 LV segments, systolic dyssynchrony index, was 69.9 milliseconds. LV ejection fraction increased from 27% at baseline to 50% after medical treatment. baseline at the end of a full cardiac cycle were selected and the direction of systolic strain was analyzed. Using peak systolic velocity and the direction of the corresponding strain, 3 different types of myocardial velocity curve could be identified (Figure 1). Type I was defined as peak systolic contraction wave with concomitant negative strain; delayed longitudinal contraction wave (the second peak in velocity tracing) resulted in negative strain peaks in both systole and diastole. Type II was defined as a curve with delayed longitudinal contraction wave with concomitant negative strain; the first peak of velocity tracing showed concomitant positive strain, suggesting passive movement rather than active contraction. Type III was defined as peak systolic or delayed longitudinal contraction wave with concomitant positive strain, suggesting no active longitudinal contraction at all. The peak systolic velocity of LV walls only with concomitant negative strain (type I or II) were measured and added to represent LC of each patient (LC by DTI) (Figures 2 and 3). Myocardial velocity curves were also reconstituted to quantify systolic dyssynchrony using 4-basal and 4-midsegmental LV model of two apical views. The time to peak systolic myocardial contraction was measured in 8 LV segments and the SD of time intervals of 8 LV segments was used as a parameter of systolic dyssynchrony.21 Statistics Numeric variables are expressed as mean ⫾ SD. Statistical analysis of difference between groups was assessed by

Student unpaired t test. The ␹2 test and Fisher’s exact test were used to compare the frequency ratios between groups. Stepwise multivariable logistic regression models were fitted using variables found to have marginal association with RR. A P value of less than .05 was considered statistically significant. Receiver operating characteristics were analyzed for LC by DTI. Intraobserver and interobserver variability of LV volume measurement was tested using baseline echocardiography of 16 patients. The correlation coefficient of intraobserver variability was 0.96 and the SE of estimation was 2.2% (P ⬍ .001). The correlation coefficient and the SE of estimate of interobserver variability was 0.92 and 2.5%, respectively (P ⬍ .001). The SD between these two measurements was ⫾2% for LV EF. In our laboratory, the intraobserver and interobserver variability for measurement of peak systolic velocity using DTI was 6.0% and 8.5%,22 and time intervals were 4.1% and 4.6%, respectively.23

RESULTS At baseline, the mean EF of the cohort of 35 patients was 26 ⫾ 7%, and the duration of their heart failure symptoms was 3.5 ⫾ 3.5 years (0.3-11 years). Medical history of hypertension and diabetes mellitus was present in 12 (34%) and 8 (23%) patients, respectively. The mean QRS duration in the electro-

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Figure 3 Representative myocardial velocity profiles (A and C) with strain measurements (B and D) for patient with left ventricular (LV) systolic dysfunction who did not achieve successful reverse remodeling. Only inferior wall (yellow) (C) showed type II pattern of delayed peak systolic velocity of 2.8 cm/s with concomitant negative strain, whereas other 3 walls showed type III pattern. Calculated longitudinal contractility index by Doppler tissue imaging was 2.8 cm/s and systolic dyssynchrony index was 39.2 milliseconds. LV ejection fraction changed from 23% at baseline to 17% after medical treatment.

cardiogram was 127 ⫾ 33 milliseconds, and 16 patients (46%) showed left bundle branch block. All patients underwent follow-up echocardiography 13.4 ⫾ 6.2 months later. With medical treatment, LV end-systolic volume changed from 140 ⫾ 66 to 144 ⫾ 119 mL (P ⫽ .882) and LV EF from 26 ⫾ 7 to 31 ⫾ 14% (P ⫽ .018). RR was observed in 13 patients (37%, group A) and baseline characteristics between patients who did and did not achieve RR (group B) are summarized in Table. Mean age (56 ⫾ 15 vs 60 ⫾ 12 years, P ⫽ .348) and initial LV EF (27 ⫾ 6 vs 25 ⫾ 8%, P ⫽ .367) was similar between groups. Compared with group B, group A showed shorter QRS interval (110 ⫾ 36 vs 136 ⫾ 28 milliseconds, P ⫽ .022), shorter symptom duration (2.3 ⫾ 3.5 vs 4.2 ⫾ 3.4 years, P ⫽ .047), lower prevalence of left bundle branch block (23% vs 59%, P ⫽ .039), and higher value of LC by DTI (9.6 ⫾ 3.5 vs 6.3 ⫾ 3.6 cm/s, P ⫽ .011). The systolic dyssynchrony index (SD of time intervals to peak systolic myocardial contraction) did not show any significant difference between groups (33.4 ⫾ 14.8 vs 38.2 ⫾ 8.7 milliseconds, P ⫽ .301). Besides these variables showing significant difference between groups, diabetes mellitus, LV enddiastolic volume, use of spironolactone, and systolic dyssynchrony index were used for stepwise multivariable logistic regression models. Multivariate analysis revealed that symptom duration less than 2 years (odds ratio ⫽ 8.0, 95% confidence interval ⫽

1.3-47.2, P ⫽ .022) and LC by DTI (odds ratio ⫽ 1.3, 95% confidence interval ⫽ 1.0-.7, P ⫽ .019) were independent predictors of RR. The best cut-off value of LC by DTI obtained by receiver operating characteristics analysis to predict RR was 7.75 cm/s (area under the curve ⫽ 0.76, 95% confidence interval ⫽ 0.59-.93, P ⫽ .010) (Figure 4) with sensitivity and specificity of 77% and 77%, respectively.

DISCUSSION Functional Improvement in Heart Failure Along with the recent clinical introduction of new pharmacologic treatments of heart failure, marked functional improvement in patients with advanced heart failure has been reported, with prevalence ranging from 18% to 36%.5-8 These observations have significant clinical impact on selecting patients for cardiac transplantation, because of the shortage of donor hearts. Baseline clinical variables associated with RR were shorter duration of symptoms,5,6 a history of hypertension,6-8 nonischemic cause of heart failure,8 absence of diabetes mellitus,7,8 carvedilol therapy,7,8 higher serum sodium level,5 and lower atrial pressure.5 The exact mechanism by which these clinical variables are related to RR is unclear, as LV remodeling, a hallmark of progressive heart failure, is a complex process incorporating

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Table Baseline characteristics in patients with reverse remodeling and those without Age, y Functional class III or IV, % Duration of symptom, y Follow-up duration, mo Hypertension, % Diabetes mellitus, % QRS duration, ms LBBB, % LV EDV, mL LV ESV, mL EF, % Sphericity index Diastolic E velocity, cm/s Diastolic A velocity, cm/s Deceleration time, ms E= velocity, cm/s E/E= Systolic dyssynchrony index, ms LC by TDI, cm/s ␤-receptor blocker, % Spironolactone, %

Total (N ⴝ 35)

Improved (N ⴝ 13)

Not improved (N ⴝ 22)

P*

57 ⫾ 16 60 3.5 ⫾ 3.5 13.3 ⫾ 6.1 34% 23% 127 ⫾ 33 46% 183 ⫾ 68 140 ⫾ 66 26 ⫾ 7 1.49 ⫾ 0.20 79 ⫾ 32 73 ⫾ 31 179 ⫾ 59 4.3 ⫾ 1.5 21 ⫾ 12 36.4 ⫾ 11.3 7.5 ⫾ 3.9 60% 57%

56 ⫾ 15 77 2.5 ⫾ 3.5 13.4 ⫾ 5.8 4/13 (31%) 5/13 (39%) 110 ⫾ 36 3/13 (23%) 162 ⫾ 47 121 ⫾ 42 27 ⫾ 6 1.53 ⫾ 0.16 77 ⫾ 36 65 ⫾ 30 173 ⫾ 68 4.5 ⫾ 1.4 18 ⫾ 10 33.4 ⫾ 14.8 9.6 ⫾ 3.5 9/13 (69%) 5/13 (39%)

60 ⫾ 12 50 4.2 ⫾ 3.4 13.3 ⫾ 6.5 8/22 (32%) 3/22 (14%) 136 ⫾ 28 13/22 (59%) 203 ⫾ 85 157 ⫾ 82 25 ⫾ 8 1.46 ⫾ 0.24 79 ⫾ 31 77 ⫾ 31 182 ⫾ 56 4.2 ⫾ 1.6 23 ⫾ 13 38.2 ⫾ 8.7 6.3 ⫾ 3.6 12/22 (55%) 15/22 (68%)

.348 .112 .047 .940 .736 .091 .022 .039 .147 .213 .367 .320 .841 .287 .702 .515 .331 .301 .011 .392 .086

A, transmitral late diastolic; E, transmitral early diastolic; E’ mitral annular early diastolic; EDV, End-diastolic volume; EF, ejection fraction; ESV, end-systolic volume; LBBB, left bundle branch block; LC by TDI, added value of peak systolic or delayed contraction velocity with concomitant negative strain among 4 different left ventricular walls; LV, left ventricular.

Figure 4 Receiver operating characteristics curve for index of longitudinal contractility of left ventricle to predict reverse remodeling. CI, Confidence interval.

many mechanical, neurohormonal, and possibly genetic factors.1,3 The clinical predictors of RR mentioned above are poor indicators of myocardial biologic function of an individual patient. Myocardial function is currently the main target of pharmacologic modification to attenuate LV remodeling and to promote RR in

patients with heart failure.1 In this study, we have shown that variable patterns of LC could be present in different LV walls in a single patient, making assessment of LC using DTI a useful independent factor for predicting RR in patients receiving medical treatment only for advanced heart failure. Our finding that a type I or II pattern of myocardial velocity curve, indicative of weak but active systolic contraction, is associated with a favorable response to medical treatment for heart failure supports the measurement of systolic peak velocity and strain as a rational way to assess regional myocardial biologic function, which varies in individual patients. It is conceivable that patients with relatively well-maintained or preserved myocardial function have a higher probability of RR than those without, making quantitative assessment of LC using DTI a unique method for the early detection of patients with a higher probability of RR. An independent association between short duration of symptoms and RR may also be indicative of the importance of the progressive and time-dependent process of LV remodeling in heart failure, which is eventually irreversible. DTI in Heart Failure Although LV volume measurement with calculation of EF remains as a marker of the remodeling process,4 it is only a surrogate for inherent myocardial biologic function. DTI is unique, as it provides a useful clinical tool for quantification of regional myocardial function and myocardial characteriza-

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tion.14,24 DTI has been extensively used especially for quantification of LC,25-28 which is accepted as an important component of the systolic performance of the LV. One of the main findings of the current study is that the pattern of LC assessed by DTI was variable in patients with severe LV dysfunction. Even in the same individual, different types of myocardial velocity curves could be observed in different LV walls, especially with analysis of strain measurement. Strain is calculated as (L ⫺ Lo)/Lo, where Lo is the original length and L is the length of end systole. When acquired from the apex, normally contracting myocardium has a negative strain. The presence of myocardial segments showing positive strain during systole, however, suggests passive movement or lengthening caused by tethering induced by other, actively contracting myocardial segments.29 The combination of tissue velocity and negative strain was used for quantification of LC in this study. As data acquisition was done at the basal segments of 4 different LV walls, peak systolic velocity gives us information about the biologic behavior of the entire wall. Although strain is a local parameter, we excluded LV walls showing positive strain and added peak systolic velocity with concomitant negative strain as a representative value for LC by DTI. According to previous reports, normal values of peak systolic velocity for basal segments of 4 different LV walls in a middle-aged population range from 5.97 to 6.59 cm/s27,28; LC by DTI in healthy control subjects should be higher than 20 cm/s, which is significantly higher than that in our patients with advanced heart failure (7.5 ⫾ 3.9 cm/s). In patients with advanced heart failure, DTI has been used to quantify mechanical dyssynchrony.17-20 DTI allows measurement of time intervals from electrical activity (QRS complex) to peak systolic velocity and early diastolic velocity of different regions of the myocardium for assessment of systolic and diastolic dyssynchrony.17,23 Mechanical systolic dyssynchrony assessed by DTI is reported to be the most powerful predictor of RR after cardiac resynchronization therapy.21 However, in this study we have failed to demonstrate any association between systolic dyssynchrony index and successful RR after medical treatment. In the previous reports,21,30 at least 10 or 12 myocardial segments were used to calculate systolic dyssynchrony index, but in this study only 4 basal LV segments were included. Considering the fact that LV dyssynchrony could be more easily demonstrated using multiple LV segments, the small number of myocardial segments used in this study is a main reason why LV systolic dyssynchrony was not an independent factor of RR. The usefulness of LC by DTI should be tested separately in patients receiving cardiac resynchronization therapy, another promising treatment modality for RR in patients with advanced heart failure.

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Study Limitations Small numbers of patients is a main limitation of this study. In addition, as only patients with nonischemic heart failure were selected in this study, the usefulness of assessment of LC using DTI to predict functional improvement is uncertain for patients with ischemic cardiomyopathy, who might show more profound dyssynchrony as a result of resting regional wallmotion abnormalities. The clinical usefulness and potential prognostic implication of LC by DTI needs to be clarified in future investigations including diverse causes of heart failure and large numbers of patients. The second important limitation is technical one. Because of significant noise of strain curves obtained by current DTI technique, quantitative analysis using peak negative systolic strain could not be done. The current system does not allow measurement of 2- or 3-dimensional strain of the entire LV wall, which might be a more ideal quantitative method for LC. Considering potential compounding variables such as translation and rotation, we did not analyze the radial function of LV in these patients. We hope further technical advances will provide an opportunity to investigate these matters seriously. Although we have demonstrated that LC by DTI is an independent predictor of RR in selected patients with nonischemic heart failure, precise explanation regarding the relationship between mechanical index of LC by DTI and biologic response of RR with medical treatment remains to be clarified. It should be tested if dissociation between LV EF and LC reported in patients with diabetes and preserved LV systolic function31 could explain the reason why EF is comparable between two groups with striking difference of LC by DTI in our study. Conclusions We have shown that variable patterns of LC in different LV walls could be easily assessed and quantified by currently available DTI. In patients with nonischemic cardiomyopathy, this information can predict functional improvement and RR resulting from medical treatment. Further study is necessary to test whether this method is useful in patients with different causes of heart failure and in those receiving different treatment modalities, such as cardiac resynchronization therapy.

REFERENCES 1. Eichhorn EJ, Bristow MR. Medical therapy can improve the biological properties of the chronically failing heart: a new era in the treatment of heart failure. Circulation 1996;94:2285-96. 2. Bristow MR. ␤-Adrenergic receptor blockade in chronic heart failure. Circulation 2000;101:558-69. 3. Jessup M, Brozena S. Heart failure. N Engl J Med 2003;348: 2007-18.

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4. Udelson JE. Ventricular remodeling in heart failure and the effect of ␤-blockade. Am J Cardiol 2004;93:43-8B. 5. Steimle AE, Stevenson LW, Fonarow GC, Hamilton MA, Moriguchi JD. Prediction of improvement in recent onset cardiomyopathy after referral for heart transplantation. J Am Coll Cardiol 1994;23:553-9. 6. Cicoira M, Zanolla L, Latina L, Rossi A, Golia G, Brighetti G, et al. Frequency, prognosis and predictors of improvement of systolic left ventricular function in patients with ‘classical’ clinical diagnosis of idiopathic dilated cardiomyopathy. Eur J Heart Fail 2001;3:323-30. 7. Cioffi G, Stefenelli C, Tarantini L, Opasich C. Prevalence, predictors, and prognostic implications of improvement in left ventricular systolic function and clinical status in patients ⬎ 70 years of age with recently diagnosed systolic heart failure. Am J Cardiol 2003;92:166-72. 8. Cioffi G, Stefenelli C, Tarantini L, Opasich C. Chronic left ventricular failure in the community: prevalence, prognosis, and predictors of the complete recovery with return of cardiac size and function to normal in patients undergoing optimal therapy. J Card Fail 2004;10:250-7. 9. Wong M, Johnson G, Shabetai R, Hughes V, Bhat G, Lopez B, et al. Echocardiographic variables as prognostic indicators and therapeutic monitors in chronic congestive heart failure: Veterans Affairs cooperative studies V-HeFT I and II, VHeFT VA cooperative group. Circulation 1993;87:VI65-70. 10. Sutton MSJ, Pfeffer MA, Plappert T, Rouleau JL, Moye LA, Dagenais GR, et al. Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction: the protective effects of captopril. Circulation 1994;89:68-75. 11. Giannuzzi P, Temporelli PL, Bosimini E, Silva P, Imparato A, Corra U, 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;28:383-90. 12. Pozzoli M, Traversi E, Cioffi G, Stenner R, Sanarico M, Tavazzi L. Loading manipulations improve the prognostic value of Doppler evaluation of mitral flow in patients with chronic heart failure. Circulation 1997;95:1222-30. 13. Cabell CH, Trichon BH, Velazquez EJ, Dumesnil JG, Anstrom KJ, Ryan T, et al. Importance of echocardiography in patients with severe nonischemic heart failure: the second prospective randomized amlodipine survival evaluation (PRAISE-2) echocardiographic study. Am Heart J 2004;147:151-7. 14. Hatle L, Sutherland GR. Regional myocardial function–a new approach. Eur Heart J 2000;21:1337-57. 15. Sogaard P, Egeblad H, Kim WY, Jensen HK, Pedersen AK, Kristensen BO, et al. Tissue Doppler imaging predicts improved systolic performance and reversed left ventricular remodeling during long-term cardiac resynchronization therapy. J Am Coll Cardiol 2002;40:723-30. 16. Sogaard P, Egeblad H, Pedersen AK, Kim WY, Kristensen BO, Hansen PS, et al. Sequential versus simultaneous biventricular resynchronization for severe heart failure: evaluation by tissue Doppler imaging. Circulation 2002;106:2078-84. 17. Yu CM, Lin H, Zhang Q, Sanderson JE. High prevalence of left ventricular systolic and diastolic asynchrony in patients with congestive heart failure and normal QRS duration. Heart 2003;89:54-60.

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18. Bax JJ, Molhoek SG, van Erven L, Voogd PJ, Somer S, Boersma E, et al. Usefulness of myocardial tissue Doppler echocardiography to evaluate left ventricular dyssynchrony before and after biventricular pacing in patients with idiopathic dilated cardiomyopathy. Am J Cardiol 2003;91:94-7. 19. Bax JJ, Marwick TH, Molhoek SG, Bleeker GB, van Erven L, Boersma E, et al. Left ventricular dyssynchrony predicts benefit of cardiac resynchronization therapy in patients with endstage heart failure before pacemaker implantation. Am J Cardiol 2003;92:1238-40. 20. Ghio S, Constantin C, Klersy C, Serio A, Fontana A, Campana C, et al. Interventricular and intraventricular dyssynchrony are common in heart failure patients, regardless of QRS duration. Eur Heart J 2004;25:571-8. 21. Yu CM, Fung JWH, Zhang Q, Chan CK, Chan YS, Lin H, et al. Tissue Doppler imaging is superior to strain rate imaging and postsystolic shortening on the prediction of reverse remodeling in both ischemic and nonischemic heart failure after cardiac resynchronization therapy. Circulation 2004;110:66-73. 22. Yang HS, Kang SJ, Song JK, Moon DH, Song JM, Kang DH, et al. Diagnosis of viable myocardium using velocity data of Doppler myocardial imaging: comparison with positron emission tomography. J Am Soc Echocardiogr 2004;17:933-41. 23. Kang SJ, Song JK, Yang HS, Song JM, Kang DH, Rhee KS, et al. Systolic and diastolic regional myocardial motion of pacing-induced versus idiopathic left bundle branch block with and without left ventricular dysfunction. Am J Cardiol 2004;93:1243-6. 24. Marwick TH. Should we be evaluating the ventricle or the myocardium? Advances in tissue characterization. J Am Soc Echocardiogr 2004;17:168-72. 25. Oki T, Tabata T, Mishiro Y, Yamada H, Abe M, Onose Y, et al. Pulsed tissue Doppler imaging of left ventricular systolic and diastolic wall motion velocities to evaluate differences between long and short axes in healthy subjects. J Am Soc Echocardiogr 1999;12:308-13. 26. Andersen NH, Poulsen SH. Evaluation of the longitudinal contraction of the left ventricle in normal subjects by Doppler tissue tracking and strain rate. J Am Soc Echocardiogr 2003; 16:716-23. 27. Nikitin NP, Witte KKA, Thackray SDR, de Silva R, Clark AL, Cleland JG. Longitudinal ventricular function: normal values of atrioventricular annular and myocardial velocities measured with quantitative 2-dimensional color Doppler tissue imaging. J Am Soc Echocardiogr 2003;16:906-21. 28. Sun JP, Popovic ZB, Greenberg NL, Xu XF, Asher CR, Stewart WJ, 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;17:132-8. 29. Sutherland GR, Kukulski T, Kvitting JE, D’hooge J, Arnold M, Brandt E, et al. Quantification of left ventricular asynergy by cardiac ultrasound. Am J Cardiol 2000;86:4-9G. 30. Cho GY, Park WJ, Han SW, Choi SH, Doo YC, Oh DJ, et al. Myocardial systolic synchrony measured by Doppler tissue imaging as a role of predictor of left ventricular ejection fraction improvement in severe congestive heart failure. J Am Soc Echocardiogr 2004;17:1245-50. 31. Fang ZY, Leano R, Marwick TH. Relationship between longitudinal and radial contractility in subclinical diabetic heart disease. Clin Sci 2004;106:53-60.