Echocardiographic evaluation of left ventricular function in ischemic heart disease Mollema, S.A.

(1)

Echocardiographic evaluation of left ventricular function in ischemic heart disease

Mollema, S.A.

Citation

Mollema, S. A. (2010, December 9). Echocardiographic evaluation of left ventricular function in ischemic heart disease. Retrieved from

https://hdl.handle.net/1887/16229

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/16229

Note: To cite this publication please use the final published version (if

applicable).

(2)

Chapter 6

relation between global left ventricular longitudinal strain assessed with novel automated function imaging and biplane left

ventricular ejection fraction in patients with coronary artery disease

Victoria Delgado, MD, Sjoerd A. Mollema, MD, Claudia Ypenburg, MD, Laurens F. Tops, MD, Ernst E. Van der Wall, MD, PhD, Martin J. Schalij, MD, PhD, Jeroen J. Bax, MD, PhD

Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands J Am Soc Echocardiogr 2008;21:1244-1250

(3)

Chapter 6

98 abstract

objective: Automated function imaging (AFI) is a novel algorithm based on speckle-tracking imaging that can be used for assessment of global longitudinal strain of the left ventricle. The purpose of this study was to evaluate the relation between global longitudinal peak systolic strain (GLPSS Avg) assessed by AFI and left ventricular (LV) ejection fraction (LVEF).

methods: The study population consisted of 222 consecutive patients with coronary artery disease (99 patients with acute ST-segment elevation myocardial infarction (STEMI) and 123 patients with advanced ischemic heart failure) and 20 age-matched control patients. LVEF was calculated by Simpson’s rule. The GLPSS Avg was obtained by AFI.

results: In the overall study group (65 ± 10 years, 77% men) mean GLPSS Avg was 11.1 ± 4.8%

and mean LVEF was 37 ± 14%. Linear regression analysis showed a good correlation between GLPSS Avg and biplane LVEF for the overall study population (r=0.83; p<0.001). However, in patients with STEMI and patients with heart failure the correlation was less strong (r=0.42 and r=0.62, respectively).

conclusion: Systolic global longitudinal strain assessed by AFI was linearly related to biplane LVEF. In patients with STEMI or heart failure, less strong correlations were observed, suggesting that these two parameters reflect different aspects of systolic LV function.

(4)

99

Relation between global left ventricular longitudinal strain assessed with novel AFI and biplane LVEF in patients with coronary artery disease

introduction

Left ventricular ejection fraction (LVEF) is a strong prognostic parameter in patients with heart disease and is an important component in the prognostic work-up of patients with coronary artery disease (1-3). For the echocardiographic quantification of systolic left ventricular (LV) function, biplane measurement of LVEF on standard 2-dimensional (2D) images using the Simpson’s rule is currently the method of preference (4). Recently, automated function imaging (AFI) was introduced as a novel method to reflect systolic LV function, based on 2D speckle- tracking imaging, by assessment of global LV longitudinal strain (5). This imaging technique is able to discriminate between active and passive myocardial motion and enables the angle- independent quantification of myocardial deformation in two dimensions.

Data concerning the relation between global LV longitudinal systolic strain with AFI and biplane LVEF as markers of systolic LV function are scarce (6). The purpose of the present study was to evaluate the relation between global LV longitudinal systolic strain assessed by AFI and biplane LVEF in a large cohort of patients with coronary artery disease with varying LVEF, rang- ing from mild to severely depressed.

mEthods

Study population and protocol

During a 1-year period, a total of 222 patients with coronary artery disease referred for 2D echocardiography were included. The overall study group consisted of patients who underwent clinically indicated echocardiography in the acute setting of ST-segment elevation myocardial infarction (STEMI patients, n=99) or chronic ischemic heart failure (n=123).

During 2D echocardiography, biplane LV volumes and LVEF were measured and global LV longitudinal strain using AFI was assessed. In the STEMI patients, echocardiography was performed within 48 hours of admission. The heart failure patients underwent echocardiography as part of the routine clinical evaluation.

Data of the patients with coronary artery disease were compared with a group of age- matched controls (n=20) selected from an echocardiographic database (7). The control group comprised patients referred for echocardiography with atypical chest pain, palpitations or syncope without murmur. In particular, only patients without structural heart disease and normal LV systolic function and dimensions were selected. Furthermore, subjects who were referred for echocardiographic evaluation of known valvular disease, murmur, or heart failure were excluded.

(5)

Chapter 6

100 Echocardiography

2D Echocardiography was performed with the patient in the left lateral decubitus position using a commercially available system (Vivid 7, General Electric Vingmed, Milwaukee, Wisconsin, USA) equipped with a 3.5-MHz transducer. Standard 2D images triggered to the QRS complex, were saved in cine-loop format. LV end-systolic and end-diastolic volumes were assessed and LVEF was calculated from the apical 4- and 2-chamber views using the Simpson’s rule (8).

Global left ventricular longitudinal strain analysis

Global LV longitudinal strain was quantified using AFI, which provides a new imaging technique based on 2D strain imaging (6). The software analyzes motion by tracking speckles (natural acoustic markers) in the ultrasonic image in two dimensions. The frame-to-frame changes of the speckles are used to derive motion and velocity. For this purpose, one single cardiac cycle is needed from each apical view (apical long axis, 4- and 2-chamber views).

First, the end-systolic frame is defined in the apical long-axis view. The closure of the aortic valve is marked and the software measures the time interval between R wave and aortic valve closure. This interval is used as a reference for the 4- and 2-chamber view loops. After defin- ing the mitral annulus and the LV apex with 3 index points at the end-systolic frame in each apical view, the automated algorithm traces 3 concentric lines on the endocardial border, the mid-myocardial layer and epicardial border, including the entire myocardial wall. The tracking algorithm follows the endocardium from this single frame throughout the cardiac cycle, and allows for a further manual adjustment of the region of interest to ensure that all myocardial regions are included throughout the cardiac cycle. The left ventricle is divided in 6 segments in each apical view and the tracking quality is validated for each segment. Then, the myocardial motion is analyzed by speckle-tracking within the region of interest.

Finally, the automated algorithm, using a 17-segment model, provides the peak systolic longitudinal strain for each LV segment in a “bull‘s eye” plot, with the average value of peak systolic longitudinal strain for each view and the averaged global longitudinal peak systolic strain (GLPSS Avg) for the complete left ventricle. In general, longitudinal strain values are presented as negative values; a larger negative value indicates a larger extent of longitudinal strain. For the purpose of the present study, the global strain values are presented as positive values.

Mean frame rate of the obtained images was 70 fps (range 40-100 fps). For global LV longitudinal strain analysis, digital cine-loops were off-line processed using commercially available software (EchoPac 6.1, GE Medical Systems, Horten, Norway).

Statistical analysis

Continuous data were presented as mean values ± SD and comparisons among groups were performed using the one-way analysis of variance test with Bonferroni post-hoc study. Cat- egorical data were presented as percentages and were compared using the c²-test. Global longitudinal strain was correlated with LVEF by linear regression analysis.

(6)

101

Reproducibility of GLPSS Avg values measured with AFI was analyzed with repeated measurements of global LV longitudinal strain by one experienced observer at two different time points and by a second experienced observer in 25 randomly selected patients (5 controls, 10 STEMI patients and 10 heart failure patients). Intra- and inter-observer agreement for global LV longitudinal strain measurements were evaluated by Bland-Altman analysis. Furthermore, intra-class correlation coefficients were used as indicators of reproducibility.

All statistical analyses were performed with SPSS software (version 12.0, SPSS Inc., Chicago, Illinois). A p value <0.05 was considered statistically significant.

rEsults

Study population

The overall study group comprised 222 coronary artery disease patients (66 ± 10 years, 177 men [80%]) and 20 controls (64 ± 13 years, 11 men [55%]). The clinical characteristics for the overall study population and for each subgroup are summarized in Table 1.

The group of patients with STEMI comprised 99 patients (65 ± 9 years, 76 men [76%]). Pri- mary percutaneous coronary intervention was performed in all patients. Mean peak levels of creatine phosphokinase and troponin T were 2369 ± 1801 U/L and 6 ± 5 μg/L, respectively. The 123 patients with chronic ischemic heart failure (67 ± 10 years, 101 men [82%]) were in stable clinical conditions and received optimal medical treatment at maximum dosages tolerated.

The control group comprised 20 patients with no evidence of structural heart disease at the echocardiographic studies.

table 1. Clinical characteristics of the study population overall (n=242)

controls (n=20)

stEmi (n=99)

heart failure (n=123)

p value

Age (yrs) 65 ± 10 64 ± 13 65 ± 9 67 ± 10 0.3

Male, n (%) 188 (77) 11 (55) 76 (76) 101 (82) 0.02

Hypertension, n (%) 79 (33) 6 (30) 37 (37) 36 (29) 0.4

Smoking, n (%) 94 (39) 1 (5) 57 (57) 36 (29) <0.001

Hypercholesterolemia, n (%) 46 (19) 2 (10) 18 (18) 26 (21) 0.5

Diabetes mellitus, n (%) 37 (15) 3 (15) 15 (15) 19 (15) 0.9

Positive family history, n (%) 68 (28) 3 (15) 38 (38) 27 (22) 0.01

Peripheral vascular disease, n (%) 41 (17) 2 (10) 26 (26) 13 (11) 0.4 Drug therapy, n (%)

Beta-blockers Ca-antagonists ACE-inhibitors/ARBs Diuretics

176 (70) 11 (4) 195 (79) 117 (48)

6 (30) 1 (5) 3 (15) 2 (10)

91 (92) 4 (4) 91 (92) 10 (10)

79 (64) 6 (5) 101 (82) 105 (85)

<0.001 0.9

<0.001

<0.001 ACE: angiotensin-converting enzyme; ARB: angiotensin receptor blocker; STEMI: ST-segment elevation myocardial infarction.

(7)

Chapter 6

102 Echocardiography

The echocardiographic characteristics of the study population are shown in Table 2. Differences in LV volumes differed significantly between the 3 subgroups. Mean LV end-systolic volume (LVESV) and end-diastolic volume (LVEDV) were largest in patients with heart failure (173 ± 68 ml and 226 ± 78 ml, respectively; p<0.0001). In STEMI patients, mean LVESV was 68 ± 21 ml and mean LVEDV measured 128 ± 34 ml. In control patients, LV volumes were smallest with a mean LVESV of 36 ± 12 ml and a mean LVEDV of 86 ± 22 ml. In addition, heart failure patients had significantly lower LVEF than the other groups of patients (24 ± 7% versus 47 ± 7% for STEMI patients and 58 ± 6% for control patients; p<0.0001).

Global left ventricular longitudinal peak systolic strain

The AFI algorithm was able to provide GLPSS Avg in all patients (Table 2). Control patients showed the highest mean GLPSS Avg being 18.3 ± 1.7% (p<0.0001 versus STEMI and heart failure patients) (Figure 1). The patients with STEMI showed a mean GLPSS Avg of 14.0 ± 3.4%.

table 2. Echocardiographic characteristics of the study population overall

(n=242)

controls (n=20)

stEmi (n=99)

heart failure (n=123)

p value

LVESV (ml) 118 ± 75 36 ± 12 68 ± 21 173 ± 68 <0.0001

LVEDV (ml) 175 ± 80 86 ± 22 128 ± 34 226 ± 78 <0.0001

LVEF (%) 37 ± 14 58 ± 6 47± 7 24 ± 7 <0.0001

GLPSS Avg (%) 11.1 ± 4.8 18.3 ± 1.7 14.0 ± 3.4 7.6 ± 3.0 <0.0001

GLPSS Avg: averaged global longitudinal peak systolic strain; LVEF: left ventricular ejection fraction;

LVEDV: left ventricular end-diastolic volume; LVESV: left ventricular end-systolic volume; STEMI: ST- segment elevation myocardial infarction.

figure 1. Average GLPSS Avg values for each group of patients are displayed in a box-plot figure. In control patients, the highest GLPSS Avg was demonstrated. In patients with STEMI, GLPSS Avg was lower, whereas patients with heart failure had the lowest GLPSS Avg. ANOVA: analysis of variance; GLPSS Avg:

averaged global longitudinal peak systolic strain; STEMI: ST-segment elevation myocardial infarction.

(8)

103

Patients with heart failure had a mean GLPSS Avg of 7.6 ± 3.0%. In Figure 2, examples of strain curves and bull’s-eye plots, providing peak systolic longitudinal strain for all LV segments, are demonstrated for the 3 patient groups.

(9)

Chapter 6

104

The intra-observer agreement for GLPSS Avg measurements was good, with an average difference of -0.3 ± 0.6% (mean ± 2SD) between repeated measurements. The intra-class correlation coefficient for intra-observer comparisons was 0.95. Similarly, agreement of measurements made by two different observers was good, with an average difference of -0.2 ± 2.6% (mean ± 2SD) and an intra-class correlation coefficient of 0.92.

Linear regression analysis demonstrated a good correlation between GLPSS Avg and LVEF for the overall study population (y=0.28x+0.88; r=0.83; p<0.001) (Figure 3).

In the group of patients with STEMI, a moderate correlation between GLPSS Avg and LVEF was observed (r=0.42) (Figure 4, panel A). Similarly, in the subgroup of patients with ischemic heart failure patients a moderate correlation between these two parameters was obtained (r=0.62) (Figure 4, panel B).

figure 2. Longitudinal strain curves and bull’s-eye plots showing segmental peak systolic longitudinal strain of representative patients from each patient group (panel A: control; panel B: STEMI; panel C: chronic ischemic heart failure). As conventionally accepted, LV segments with normal strain (highest values of GLPSS) are presented in red and those LV segments with abnormal strain (lowest values of GLPSS) are presented in blue. The bull’s eye plot of the control patient shows high and homogeneous peak systolic longitudinal strain for the entire left ventricle. In the patient with STEMI, decreased peak systolic longitudinal strain is observed in the inferoseptal LV segments consistent with the region of infarction and the culprit coronary artery (right coronary artery). The bull’s eye plot of the patient with heart failure shows a globally reduced peak systolic longitudinal strain. GLPSS:

global longitudinal peak systolic strain; LV: left ventricular; STEMI: ST-segment elevation myocardial infarction.

(10)

105 discussion

The main findings of the present study can be summarized as follows: 1) assessment of global LV longitudinal strain with AFI can be applied in a heterogeneous study population with coronary artery disease to evaluate global systolic LV function, 2) assessment of global LV longitudinal

25

Figure 3. Relation between GLPSS Avg and LVEF presented for the overall study population (▲ = controls; ○ = STEMI; ● = heart failure).

GLPSS Avg: averaged global longitudinal peak systolic strain; LVEF: left ventricular ejection fraction; STEMI: ST segment elevation myocardial infarction.

figure 3. Relation between GLPSS Avg and LVEF presented for the overall study population (▲ = controls;

○ = STEMI; ● = heart failure). GLPSS Avg: averaged global longitudinal peak systolic strain; LVEF: left ventricular ejection fraction; STEMI: ST-segment elevation myocardial infarction.

figure 4. Relation between GLPSS Avg and LVEF presented for patient subgroups: STEMI patients (panel A) and heart failure patients (panel B). GLPSS Avg: averaged global longitudinal peak systolic strain; LVEF:

left ventricular ejection fraction; STEMI: ST-segment elevation myocardial infarction.

(11)

Chapter 6

106

strain using AFI is highly reproducible, and 3) a good relation is observed between global LV longitudinal strain assessed with AFI, and biplane LVEF.

Relevance of systolic left ventricular function in patients with coronary artery disease

In several studies, a strong relation has been demonstrated between systolic LV function and prognosis in a number of different clinical conditions (2,9,10). Particularly in patients with coronary artery disease, LVEF is the strongest predictor of long-term survival (11-13). In patients with stable angina, the annual mortality rate exceeds 3% for those patients with LVEF <35%

(10,14). In addition, Bennet et al., evaluating 94,558 patients with high-risk non-ST-elevation acute coronary syndrome enrolled in the CRUSADE trial, found a significantly higher adjusted mortality in patients with LVEF <40% than in those patients with preserved LVEF (adjusted OR 2.76, 95% CI 2.48-3.07) (3,15). Furthermore, in several large clinical trials evaluating different therapeutic strategies (e.g. renin-angiotensin-aldosteron inhibitors or implantable cardioverter- defibrillators) LVEF was used for the selection of patients (16-18).

Because of its wide availability and safety, 2D echocardiography is the most frequently used imaging modality for the quantification of systolic LV function. Several echocardiographic parameters have been used to evaluate systolic LV function: LVEF, wall motion score index and mitral annular peak systolic velocity assessed with tissue Doppler imaging (4,19,20). However, biplane LVEF quantified using the Simpson’s rule is the most widely used parameter in epide- miological and clinical trials (4).

Relation between LVEF and global left ventricular longitudinal strain

Although LVEF constitutes a simple method to study systolic LV function accurately and with high reproducibility, this parameter does not always reflect the actual extent of myocardial damage after infarction. Therefore, in patients with extensive myocardial infarction, the pres- ence of regional hyperkinesis may result in almost normal LVEF, thereby affecting the prognostic value of this parameter (21). Consequently, the assessment of regional LV function has been proposed as a more sensitive method to detect systolic LV dysfunction. Thus, wall motion score index, a semi-quantitative method to assess regional myocardial function using 2D echocardiography, has been demonstrated to provide incremental predictive value for morbidity and mortality as compared to biplane LVEF (22). However, this approach is based on a subjective visual assessment of regional wall motion.

In contrast, strain and strain rate imaging measure the magnitude and rate of regional myocardial deformation, respectively. Both imaging methods enable the differentiation between those myocardial segments with an active contraction and those that are tethered by other segments (23). The AFI algorithm is a novel method based on 2D strain imaging that enables the quantification of myocardial strain simultaneously in different LV segments with ultrasound beam angle-independency by tracking acoustic pixels equally distributed within the myocardial wall. As applied to apical views, this method allows for the measurement of regional myocardial

(12)

107

shortening and, subsequently, enables the calculation of global LV longitudinal strain as the average of the 17-segment longitudinal peak systolic strain values.

In the present study, a broad spectrum of patients with coronary artery disease was studied including patients with acute myocardial infarction and patients with chronic ischemic heart failure. Biplane LVEF was measured in all patients and used as a reference parameter to assess the clinical usefulness of a novel algorithm, global LV longitudinal strain quantified using AFI, to study global systolic LV function. The mean global LV longitudinal strain was linearly related to biplane LVEF in the overall population.

Several previous studies have demonstrated a good correlation between global LV longitudinal strain measured with speckle-tracking imaging and wall motion score index (5,6). Reisner et al. found significant lower values for average global longitudinal strain in 27 consecutive patients with myocardial infarction as compared to control patients (14.7 ± 5.1% versus 24.1

± 2.9%; p<0.0001) (5). Furthermore, the authors demonstrated a good correlation between global longitudinal strain and wall motion score index (r=0.68; p<0.0001).

Of note, the present study is the first to relate a global value for LV longitudinal strain with biplane LVEF. Between these two parameters, a good relation was observed in a heterogeneous study population with coronary artery disease.

In addition, measurement of global LV longitudinal strain was feasible in all patients. No patient had to be excluded due to poor image quality. The intra-observer and inter-observer variability were studied and good agreement was noticed. Therefore, measurement of global LV longitudinal strain using AFI provides reproducible assessment of systolic LV function. Ideally, an independent measurement of LV longitudinal strain by another technique would be desir- able to evaluate the accuracy of the novel AFI method based on speckle-tracking imaging. This was not available in the current study, but previous work validated speckle-tracking-derived strain against sonomicrometry and tagged magnetic resonance (24).

Although the correlation between the GLPSS Avg and biplane LVEF was good in the overall population, in patients with coronary artery disease (STEMI or chronic heart failure) the correlation was less strong. This observation suggests that the 2 parameters are not identical, but rather reflect different aspects of systolic LV function.

Finally, outcome data of coronary artery disease patients were not systematically recorded and therefore, the prognostic value of GLPSS Avg could not be determined in the present study.

conclusions

Global LV longitudinal strain assessed with AFI is linearly related to biplane LVEF. AFI allows reproducible quantification of systolic LV function. In patients with ischemic heart disease, a less strong correlation between GLPSS Avg and biplane LVEF was observed, suggesting that

(13)

Chapter 6

108

these two parameters reflect different aspects of LV systolic function. In this perspective, addi- tional studies are needed to evaluate the clinical implications.

(14)

109 rEfErEncEs

1. Antman EM, Anbe DT, Armstrong PW et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary: a report of the American College of Cardiol- ogy/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation 2004;110:588-636.

2. Quinones MA, Greenberg BH, Kopelen HA et al. Echocardiographic predictors of clinical outcome in patients with left ventricular dysfunction enrolled in the SOLVD registry and trials: significance of left ventricular hypertrophy. Studies of Left Ventricular Dysfunction. J Am Coll Cardiol 2000;35:1237-44.

3. Bennett KM, Hernandez AF, Chen AY et al. Heart failure with preserved left ventricular systolic function among patients with non-ST-segment elevation acute coronary syndromes. Am J Cardiol 2007;99:1351-6.

4. Gottdiener JS, Bednarz J, Devereux R et al. American Society of Echocardiography recommendations for use of echocardiography in clinical trials. J Am Soc Echocardiogr 2004;17:1086-119.

5. Reisner SA, Lysyansky P, Agmon Y, Mutlak D, Lessick J, Friedman Z. Global longitudinal strain: a novel index of left ventricular systolic function. J Am Soc Echocardiogr 2004;17:630-3.

6. Leitman M, Lysyansky P, Sidenko S 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.

7. Pereira AM, van Thiel SW, Lindner JR et al. Increased prevalence of regurgitant valvular heart disease in acromegaly. J Clin Endocrinol Metab 2004;89:71-5.

8. Lang RM, Bierig M, Devereux RB et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocar- diography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440-63.

9. Chuang ML, Hibberd MG, Salton CJ et al. Importance of imaging method over imaging modality in noninvasive determination of left ventricular volumes and ejection fraction: assessment by two- and three-dimensional echocardiography and magnetic resonance imaging. J Am Coll Cardiol 2000;35:477-84.

10. Mock MB, Ringqvist I, Fisher LD et al. Survival of medically treated patients in the coronary artery surgery study (CASS) registry. Circulation 1982;66:562-8.

11. Risk stratification and survival after myocardial infarction. N Engl J Med 1983;309:331-6.

12. Fox K, Garcia MA, Ardissino D et al. Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J 2006;27:1341-81.

13. Volpi A, De Vita C, Franzosi MG et al. Determinants of 6-month mortality in survivors of myocardial infarction after thrombolysis. Results of the GISSI-2 data base. The Ad hoc Working Group of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-2 Data Base. Circula- tion 1993;88:416-29.

14. Emond M, Mock MB, Davis KB et al. Long-term survival of medically treated patients in the Coronary Artery Surgery Study (CASS) Registry. Circulation 1994;90:2645-57.

15. Hoekstra JW, Pollack CV, Jr., Roe MT et al. Improving the care of patients with non-ST-elevation acute coronary syndromes in the emergency department: the CRUSADE initiative. Acad Emerg Med 2002;9:1146-55.

16. Pfeffer MA, Braunwald E, Moye LA et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992;327:669-77.

17. Pitt B, Remme W, Zannad F et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309-21.

(15)

Chapter 6

110

18. St John SM, Pfeffer MA, Plappert T 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.

19. Slotwiner DJ, Devereux RB, Schwartz JE et al. Relation of age to left ventricular function in clinically normal adults. Am J Cardiol 1998;82:621-6.

20. Sokmen G, Sokmen A, Duzenli A, Soylu A, Ozdemir K. Assessment of myocardial velocities and global function of the left ventricle in asymptomatic patients with moderate-to-severe chronic aortic regur- gitation: a tissue Doppler echocardiographic study. Echocardiography 2007;24:609-14.

21. Kjoller E, Kober L, Jorgensen S, Torp-Pedersen C. Long-term prognostic importance of hyperkinesia following acute myocardial infarction. TRACE Study Group. TRAndolapril Cardiac Evaluation. Am J Cardiol 1999;83:655-9.

22. Thune JJ, Kober L, Pfeffer MA et al. Comparison of regional versus global assessment of left ventricular function in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction: the valsartan in acute myocardial infarction echocardiographic study. J Am Soc Echocardiogr 2006;19:1462-5.

23. Edvardsen T, Gerber BL, Garot J, Bluemke DA, Lima JA, Smiseth OA. Quantitative assessment of intrin- sic regional myocardial deformation by Doppler strain rate echocardiography in humans: validation against three-dimensional tagged magnetic resonance imaging. Circulation 2002;106:50-6.

24. Amundsen BH, Helle-Valle T, Edvardsen T et al. Noninvasive myocardial strain measurement by speckle tracking echocardiography: validation against sonomicrometry and tagged magnetic resonance imaging. J Am Coll Cardiol 2006;47:789-93.