Introduction
The estimated prevalence of ischemic heart disease (IHD) in the United States is about 17,600,000 and 1020000 of them suffer from angina pectoris (1). Nowadays, IHD is the major cause of death worldwide, while more than half of the deaths attributed to cardiovascular disease are the result of IHD (2). Its debilitating effects on a country economy and its attitude toward developing and poor socioeconomic regions necessitate its early diagnosis and treatment via different modalities (3).
In our country, the minister of health and medical education announced that 43.7% of all-cause mortality was cardiovascular related (2). Myocardial perfusion scan are commonly used in daily practice Echocardiography in order to measure global left ventricular (LV) function stress, both at rest and during resting and stress wall motion abnormalities (4).
In 1989, tissue doppler imaging (TDI) was introduced as a novel technique for assessing both the systolic and diastolic functions of the myocardium. It is excessively being used in stress echocardiography today (5). Regarding that, the myocardial tissue exhibits much lower velocities and greater amplitudes in comparison to blood; therefore, doppler ultrasound uses high frame rates. Since its presentation, TDI spectrum of usage extended from pulse tissue acquisition toward color-coded images.  Perhaps the strongest application of TDI is its usage in stress echocardiography for assessing myocardial functional reserve. In addition, TDI of the mitral annulus has a good relationship with global systolic and diastolic functions and is able to assess regional myocardial function by placing the sample volume in the aimed segment. TDI is mostly applied for determination of myocardial relaxation and LV diastolic function (6).
Tissue doppler imaging in form of strain and strain rate is used in stress echocardiography and quantifies regional myocardial function on the basis that 5 seconds after ischemia onset, myocardial velocities decreases (7).
This paper aims to have a brief review on the role of TDI in coronary artery disease (CAD) patients.

Method and Data
All the reviewed articles were obtained from MEDLINE (up to January 2013). All were controlled trials with consensus on patients with CAD confirmed by selective coronary angiography. The studies had focused on those documented CAD cases without any previous history of myocardial infarction and with normal LV systolic function.
Most data extracted by tissue doppler imaging focused on maximum systolic (s) velocity, maximum early diastolic (e) velocity or maximum late diastolic (a) velocity. The diastolic parameter E/e (the ratio of early diastolic transmitral flow velocity and early diastolic tissue velocity) was also analyzed.
The results and the study characteristics of seven articles were reviewed. The collected data have been summarized in Table 1.

Tissue doppler at rest
Bolognesia et al detected significant reduced systolic peak velocity (13±0.9 vs 11.2±2), significant early diastolic peak velocity (17±1.4 vs 12.6±2.5) and non-significant late diastolic peak velocity (13.3±1.6 vs 12.2±2.4) in patient group. Peak E velocity (cm/s) was also significantly reduced in CAD patients (75±13.2 vs 55.2 ±12). They suggested that in early stages of ischemic LV, while LVEF is still normal, some abnormalities in systolic and diastolic functions are already present, which can be detected by tissue doppler imaging. Peak Em velocity is a reliable marker of diastolic dysfunction. It has linear reverse relationship with diastolic function whereas peak E velocity does not. Therefore, tissue doppler imaging is more sensitive than conventional transmitral doppler flow in CAD patients (7).
Dounis et al published an article focused on patients with diabetes type 2 and compared it among four groups of 66 patients including control, type 2 diabetic, CAD and diabetic subjects with CAD (DCAD). Pulsed tissue doppler was utilized for the assessment of systolic and diastolic myocardial velocities. In 20 patients, angiography had not been done. Therefore, they underwent traditional stress echocardiography. Twelve  myocardial segments were assessed by TDI and were matched with the involved territories of stenotic coronary arteries.
In type 2 diabetic patients compared to controls, Ve was reduced at rest and during stress (P=0.02). This was also true for CAD patients and DCAD patients compared to the control group (P=0.001). Vs was also reduced in CAD and DCAD patients (P=0.008).
This study revealed that Ve reduced in the diabetic group to the same degree as the CAD patients but Vs was not significantly impaired in this study. Diastolic dysfunction was attributed to macro/microvascular dysfunctions, which can be alleviated by preventive strategies (10).
Hoffman et al, in 2010, tried to find out whether the distinct pattern of tissue doppler had any relationship with the severity of coronary artery stenosis. Fourty-seven patients with stable angina and 35 controls were involved. Single vessel disease was defined as only left anterior descending (LAD) stenosis and 2 vessel disease patients were those with LAD and left circumflex artery (LCX) stenosis. 6 mitral annular regions were assessed to obtain tissue doppler parameters.
Global diastolic (E/e) and systolic (s velocity) functions were impaired with respect to increased severity. Early diastolic velocity (e) reduced in SVD and 2VD patients but was normal in 3VD cases. Late diastolic velocity (a) increased in SVD patients but not in 2VD and 3VD cases. Significant regional systolic velocity (s) especially in 3VD ischemic segments reduced significantly, whereas in SVD and 2VD patients it reduced to a lesser degree. In addition, significant reduction of e velocity in SVD and 2VD patients in the anterior and anteroseptal walls was recognized (11).
Golmohammadi et al in Iran performed a study for the prediction of severity of coronary stenosis by tissue doppler in the absence of infarction. They examined 73 patients without history of previous MI, atrial fibrillation and left bundle branch block. TDI velocities (SV, E’V and A’V) were measured at 6 basal segments of LV. Peak mitral inflow early diastolic velocity (mitral E) and peak late diastolic velocity (mitral A), deceleration time of mitral E velocity and E/A ratio were measured by doppler imaging. They concluded that TDI study was not sensitive enough in the diagnosis of coronary stenosis (13).

Tissue doppler at stress
Madler et al. in 2003, applied tissue doppler imaging in stress echocardiography as a noninvasive technique for diagnosis of CAD. They evaluated 289 patients, 92 subjects previously known to be normal, 48 subjects had known coronary disease and the remaining 149 patients were referred because of chest pain. Five segments were excluded due to unreliable off line velocities. The sensitivity and specificity of regression models achieved for each territory were as follows: 80% and 80% for LAD disease, 91% and 80% for LCX and 93% and 82% for RCA, respectively; giving a high negative predictive value especially for the exclusion of LCX and RCA. In this study, only peak systolic velocity was evaluated which was adjusted for maximal heart rate, age and sex (8). Williams et al. in 2005 selected 26 patients and compared them with 12 controls to investigate whether tissue doppler strain and strain rate changed in the stunned myocardium after stress echocardiography. Nine patients had SVD, another 9 had 2VD and 8 had 3VD, giving totals of 23 patients with LAD disease, 16 with LCX and 12 with RCA disease. Tissue doppler parameters in the base of the anterior  segment were assessed in 16 patients with documented proximal LAD lesions (9). Peak systolic velocity showed a lower rise in the base of the anterior segment in the study group versus the controls right after maximum exercise (31% vs. 92%). Diastolic velocity did not rise in the study group despite the increase in the control group. Strain and strain rate reduced at peak exercise whereas the control group exhibited increased amplitude. Both early and late diastolic strain responses were blunted in the study group and in the reverse direction. Dysfunctional stunned myocardium manifested in this study after an exercise episode (9).
Zagatina et al. studied 106 patients and 17 controls aimed to obtain quantitative diagnostic criteria for TDI in order to detect CAD in stress echocardiography. They used pulse doppler in 8 LV segments by excluding the apical segments because of low accuracy. They assessed LAD and LCX territories matched with their angiography. Visual interpretation of regional wall motion abnormalities depended on the observer experience. TDI provided less interobserver variability and helped especially in situations such as poor quality image, subtle abnormalities in motion and marginal lesions.
Systolic velocities had a greater correlation with coronary artery stenosis than diastolic velocities. Two segments of LAD and one segment of LCX revealed a relationship with the stenosis (11).

Discussion
A review article recently published by Agarwal et al. analyzed the use of tissue doppler imaging in coronary artery disease.  Few studies have focused on this subject all over the world and have shown major heterogeneity in their results, most probably due to differences in study populations, echocardiography devices, mode of doppler used, degree of hypertensive patients and LVH, and the modality used to confirm CAD beside angiography. All such studies were controlled trials in which the cut off point for tissue doppler values were not achieved (14).
This review article supported the use of systolic parameters of tissue doppler study at rest combined with wall motion indices, which gave a quantitative parameter rather than just a qualitative parameter for CAD detection. It even concluded that there was not only a relationship between systolic velocity and CAD, but abnormal velocities showed more severe degrees of CAD (14).   
Systolic velocity is both sensitive and specific in detecting regional myocardial dysfunction comparing weak relationship with diastolic function. In just one study during dobutamine stress echocardiography, early diastolic velocity reduction was more sensitive than systolic velocity for the detection of CAD (15).
Myocardial relaxation is an energy consuming process, which is affected by ischemia even earlier than systolic function (16). Animal model studies have established this fact previously (17). TDI could detect diastolic dysfunction at rest if recurrent ischemia induced structural changes exist (18). Regional e velocity reduction in SVD and 2VD was detected in one of the studies, which assessed CAD degree and its correlation with tissue Doppler parameters, but in 3VD increased LV pressure neutralized this regional effect.  This conclusion is true for the segments in the center of the ischemic  region whereas peripheral regions may be supplied by the other nonstenotic or collateral vessels. E/e velocity had also a direct relationship with CAD severity, a marker of global diastolic function. It can also be explained by recurrent ischemia and its following consequences.
Hoffman et al. drew the final conclusion that even single regional reduced systolic or diastolic velocities should bring up the possible diagnosis of ischemia in the cardiologist mind (11).
In two studies by Hoffman et al. it was shown that incremental values of tissue doppler in patients with stable angina in addition to exercise tolerance test and single photon emission computed tomography (SPECT) and improved their sensitivity (15,16).
ACC/AHA guideline stated that TDI is largely beneficial because it is both available and quantitative (17).
Further studies are needed to brighten the use of TDI in CAD patients and in the assessment of their disease severity.

Acknowledgement
We would like to thank Clinical Research Development Center of Ghaem Hospital for their assistant in this manuscript. This study was supported by a grant from the Vice Chancellor for Research of the Mashhad University of Medical Sciences for the research project as a medical student thesis with approval number of 910401.

Conflict of Interest
The authors declare no conflict of interest.