Can Tei Index Predict High Syntax Score in Patients with Chronic Coronary Syndrome and Normal Left Ventricular Systolic Function?

OBJECTIVE: Some patients who had chronic coronary syndrome (CCS) and were recognized as low risk, however, developed cardiovascular events, whereas others who were categorized as high risk did not develop any cardiovascular events. Invasive coronary angiography is the gold standard tool for the assessment of coronary artery disease (CAD) severity. The SYNTAX score (SS) was recently recognized as an invasive angiographic-guided scoring system used in risk stratification of patients who have more than one-vessel CAD and undergoing revascularization with percutaneous cardiovascular intervention. It has a good predictive value of adverse cardiovascular events. Exploration for unique noninvasive modalities that may help in a better way for risk stratification of CCS patients by predicting the severity of CAD (as reflected by SS) would be of a paramount value. Tei index is a promising modality for that objective, which is a Doppler-derived time interval index that combines both systolic and diastolic cardiac performance.
METHODS: We examined the relationship between the severity of CAD as assessed by the SS and Tei index in 100 patients with CCS and normal left ventricular systolic function.
RESULTS: All the studied 100 patients had a normal ejection fraction with mean = 58.92 ± 7.88; the mean value of Tei index was 0.84 ± 0.26. There was a statistically significant positive association between Tei index and SS (P = 0.0001); moreover, there was a correlation between left anterior descending (LAD) affection and Tei index (P = 0.0001).The cutoff point of Tei index to detect SS above 22 was >0.93 (with specificity of 86.5% and sensitivity of 42.4%).
CONCLUSION: Tei index significantly correlates with SS and LAD affection. Moreover, it is a cheap, radiation-free, noninvasive technique and may be used as a further risk stratification modality beyond others. Copyright:

INTRODUCTION

Coronary artery disease (CAD) is the chief reason for morbidity and mortality worldwide, and its prevalence has been prominently increasing. The severity of CAD can be evaluated by many modalities including anatomically by direct assessment of any coronary blockage, functionally by assessing the amount of blood delivered to myocardium, and clinically by defining symptoms consistent with insufficient blood supply.[1]

The SYNTAX score (SS) is an angiographic grading modality designed to evaluate the severity of CAD. It aids in revascularization decisions and prediction of MACE in patients with CAD.[2]

CAD causes left ventricular (LV) systolic and diastolic dysfunction which can be evaluated by echocardiography. Many studies have demonstrated that diastolic dysfunction develops in patients with chronic coronary syndrome (CCS) independent of LV systolic function.[3]

The myocardial performance index (MPI) (Tei index) has been commonly used to imitate global cardiac function rather than systolic or diastolic function alone, and it evaluates independently the myocardial performance of the left and right ventricles.[4]

Tei index has been evaluated in several cardiac conditions such as heart failure, myocardial infarction, hypertension, and diabetes mellitus and was found to anticipate both altered morbidity and mortality consequences.[56] Although the significance of Tei index in patients who had myocardial infarction is well established, the relationship between Tei index and the severity of CAD in patients with CCS has not been clearly appreciated.[5]

METHODS

Aim of the work

The aim of this study is to examine the correlation between the severity of CAD as assessed by SS and Tei index in patients with CCS.

Study design

This cross-sectional observational study included 100 patients with CCS and normal LV function presented to the Cardiology Department of our University Hospital to perform elective coronary angiography (CA).

Inclusion criteria

All patients presented with CCS and normal LV systolic function and having more than 70% stenosis in at least one vessel of more than 1.5 mm in diameter.

Exclusion criteria

Patients with previous acute coronary syndrome

Patients with heart failure (even with preserved ejection fraction [EF])

Patients with LV hypertrophy

Atrial fibrillation

Patients with significant valvular disease

Patients with a history of coronary artery bypass graft or percutaneous coronary intervention.

Setting of the study

After the approval of our ethical committee, informed consent was obtained from all patients

All patients in this study were subjected to full history taking with stress on history of risk factors for CAD

Complete clinical examination including general and local cardiac examination

Electrocardiography (ECG): 12-lead ECG for all patients

CA and SS calculation: This was done using an online calculator available at (www.SYNTAX.com) with low SYNTAX ranged: 0–22, intermediate SYNTAX was 23–32, and high SYNTAX was >32[7]

Transthoracic echocardiography.

LV dimensions and volumes and LV EF

Doppler measurements: A sample volume is placed at mitral valve (MV) tips, with optimal alignment of pulsed Doppler with blood flow obtaining E and A velocities to calculate E/A ratio. Normally, it ranged from 0.8 to 2.

Grades of diastolic dysfunction:

Grade I: If E/A ≤0.8

Grade II: Diagnosed if E/A was normal at first, then with Valsalva or any maneuver that decreases preload, it became ≤0.8

Grade III: If E/A more than 2.

Tissue Doppler measurements: Sample volume was placed at lateral mitral annulus in apical 4 chamber view. The First positive wave was (S), while the first negative one was(E'). Moreover the second negative wave was (A').(E') velocity was used to obtain E/lateral E' ratio. Normally, it is <13, ratio >13 was considered abnormal.

(Tei Index) or MPI

Tei index was calculated by placing pulsed wave Doppler in the apical five chamber view between mitral Valve and aortic valve to express both the aortic out flow pattern and mitral in flow pattern, thus iso-volumetric contraction time (IVCT), ejection time (ET), and iso-volumetric relaxation time (IVRT) can be calculated. Tei index is calculated as: a (IVCT + IVRT + ET)−b (ET)/b (ET). The normal value of the Tei index of LV was <0.40 [Figure 1].[8]

Figure 1

Schematic representation of the measurement of the Tei index. a: time interval from the end to the start of transmitral flow, b: left ventricular ejection time (also denoted by ejection time), c: time interval from the peak of the R wave on the ECG to the start of transmitral flow, d: time interval from the peak of the R wave on the ECG to the end of ejection time, ejection time: (b) left ventricular ejection time, IVCT: Isovolumic contraction time, IVRT: Isovolumic relaxation time, ECG: Electrocardiography[8]

Statistical analysis

Categorical variables were expressed as number (%) and continuous variables were expressed as mean ± standard deviation. The independent sample t-test and ANOVA were used to compare the mean values of different groups. Linear regression was used for correlation analyses for all tests, P <0.05 was considered statistically significant, and all the analyses were performed using commercially available software (SPSS version 16.0; SPSS, Inc., Chicago, IL, USA).[9] A receiver operating characteristic curve (ROC) is a graphical plot that illustrates the diagnostic ability of a binary classifier system as its discrimination threshold is varied that will be used to determine the cutoff point for tested parameters and their sensitivity and specificity.[10]

RESULTS

Demographic data

The study population included 14 females (14%) and 86 males (86%) with a mean age 49.85 ± 5.94, mean BMI 29.7 ± 2.88, the percentage of hypertensive patients was 62%, and the diabetics were 37 patients [Table 1].

Table 1

Demographic data of the studied patients

Variables	Variables	n=100
Sex	Females	14 (14%)
	Males	86 (86%)
Age (yrs)	Mean±SD	49.85±5.94
DM	Positive	37
HTN	Positive	62
BMI (Ht/m2)	Mean±SD	29.72±2.88
Smoker	Positive	33
CKD	Positive	11

Echocardiographic findings

All the studied population had a normal EF with a mean of 58.92 ± 7.88, the mean value of Tei index of 0.84 ± 0.26, and other echocardiographic findings are expressed in Table 2.

Table 2

Echocardiographic parameters among the studied patients

Variables	Variables	n=100
EDV (ml)	Mean±SD	114.31±37.89
ESV (ml)	Mean±SD	50.73±25.59
EDD (mm)	Mean±SD	51.78±6.82
ESD (mm)	Mean±SD	35.04±6.90
EF (%)	Mean±SD	58.92±7.88
E/A	Mean±SD	0.95±0.40
E/E`	Mean±SD	7.03±2.59
IVCT (ms)	Mean±SD	85.23±35.17
IVRT (ms)	Mean±SD	127.94±28.64
ET (ms)	Mean±SD	252.94±37.51
Tei Index	Mean±SD	0.84±0.26

The studied population was divided according to diastolic dysfunction into normal diastolic function, Grade I diastolic dysfunction, and Grade II diastolic dysfunction representing 44.8%, 52.2%, and 2% of the patients, respectively.

SYNTAX score

The mean SS was 19.84 ± 6.56. Patients were divided into two groups according to SS score: low SS (≤22) group which included 67 patients (67%) and intermediate SS group (23–32) included 33 patients (33%). There were no patients with high SS in the study.

Correlations between Tei index and coronary anatomy

Based on CA, the studied population was furtherly classified into left anterior descending (LAD) and non-LAD groups. There was a statistically significant difference between LAD and non-LAD groups as regards the Tei index [Table 3].

Table 3

Comparison between LAD and non-LAD groups as regard Tei index

	Non LAD n=27	LAD n=73	Independent t-test
			t	P
Tei Index	0.63±0.12	0.91±0.25	-5.699	0.000

Based on CA, the studied patients were subdivided according to the number of affected vessels into three groups. There were statistically significant differences between all of these groups as regards the Tei index with greater mean value in the group of more than two-vessel disease [Table 4].

Table 4

Comparison between the Tei index and number of vessels affected

	One vessels n=13	Two vessels n=13	More than two vessels n=74	One Way ANOVA test
				F	P
Tei Index	0.60±0.16	0.65±0.06	0.91±0.25	16.130	0.000

Comparison between groups of SYNTAX score and different echo parameters

As regards diastolic dysfunction, there was no statistically significant correlation with SS (P = 0.44). Moreover, there was no statistically significant difference between low and intermediate SS regarding echocardiographic parameters of the studied patients [Table 5].

Table 5

Comparison between low and intermediate Syntax score as regard different echocardiographic parameters of the studied group

	Mean±SD		Independent t-test
	Low SYNTAX score	Intermediate SYNTAX score	t	P
EDV (ml)	115.77±40.38	111.39±32.75	0.540	0.590
ESV (ml)	53.64±25.51	44.91±25.14	1.612	0.110
EDD (mm)	51.91±7.03	51.50±6.46	0.277	0.782
ESD (mm)	35.68±6.76	33.72±7.09	1.327	0.188
EF (%)	58.12±7.67	60.55±8.16	-1.457	0.148
E/A	0.96±0.41	0.93±0.39	0.315	0.753
E/lat E`	7.20±2.88	6.68±1.89	0.941	0.349
IVCT ms	86.33±40.47	83.00±20.98	0.443	0.659
IVRT ms	125.30±27.42	133.30±30.71	-1.319	0.190
ET ms	256.37±35.67	245.97±40.67	1.309	0.194
Tie Index	0.81±0.27	0.89±0.22	-1.430	0.156
GLSS	-12.07±5.18	-10.75±5.15	-1.202	0.232

On the other hand, there was a positive correlation between SYNTAX and Tei index (r = 0.495, P < 0.01). Likewise, there was a positive correlation between SS and E/E' (r = 0.20, P = 0.04). Moreover, there was a positive correlation between IVRT and SS (r = 0.39, P < 0.01). Furthermore, there was a positive correlation between ET and SS (r = −0.262, P < 0.009), while there was a negative correlation between SS and E/A (r = −0.04, P = 0.65) [Table 6].

Table 6

Correlation between SYNTAX score and the studied parameters in all patients

	SYNTAX score
	R	P
Age (yrs)	0.026	0.794
Height (m)	0.015	0.880
Weight (kg)	0.161	0.109
BMI (Ht/m2)	0.142	0.161
EDV (ml)	0.019	0.849
ESV (ml)	-0.069	0.496
EDD (mm)	0.049	0.631
ESD (mm)	-0.011	0.915
EF (%)	0.050	0.620
E/A	-0.045	0.655
E/E`	0.202	0.044
IVCT (ms)	0.111	0.271
IVRT (ms)	0.394	0.000
ET (ms)	-0.262-	0.009
Tei Index	0.495	0.001

Receiver operating characteristic curve

ROC curve analysis was done to determine the cutoff point for the Tei index and its specificity and sensitivity to detect the SS above 22. The cutoff point of Tei index was >0.93 (with a sensitivity of 42.4% and specificity of 86.5%) [Table 7].

Table 7

Cut off values for Tei index

	Cut off point	AUC	Sensitivity+	Specificity-	PPV	NPV
Tei Index	>0.93	0.637	42.42	86.57	60.9	75.3

DISCUSSION

Nowadays, the prevalence of ischemic heart disease (IHD) is gradually increasing which is related to many reasons such as stressful sedentary life, unhealthy food habits, and increased prevalence of HTN and DM among the population. CCS is one of the most common forms of IHD.[11]

Myocardial revascularization exhibits fundamental impacts, such as improvement in symptoms, functional status, and/or quality of life, outweighs the expected negative consequences of the procedure. Therefore, it is paramount to have risk assessments in clinical practice, which display a great value; therefore, so many risk stratification models were constructed.[12]

Some patients who had CCS and were recognized as low risk, however, developed cardiovascular events, whereas others who were categorized as high risk did not develop any cardiovascular events.[13]

Invasive CA is the gold standard tool for the estimation of CAD degree.[14]

The SS is a lesion-based angiographic grading tool used to assess the severity of CAD in CCS patients. It aids in revascularization decisions and risk stratification. Moreover, it predicts mortality and morbidity in patients with CAD.[2]

Finding a unique noninvasive modality for predicting the severity of CAD (as reflected by SS) in patients with CCS could be of fruitful value by risk stratifying them and anticipating who are more prone for cardiovascular events. Therefore, applying more invasive procedures for them could be more logical.

Ischemia causes LV systolic and diastolic dysfunction which can be evaluated by echocardiography. Many studies have verified that diastolic dysfunction develops in patients with CCS independent of LV systolic function.[15]

Conventional echocardiographic indices that are usually useful for the estimation of cardiac function show some limitations. LV EF is the most consistent estimator of systolic function. Howver, when the elliptical cardiac chamber is distorted to a spherical one, the accuracy of EF tends to be low.[16] On the other hand, transmitral flow, which is the most regular tool for assessment of diastolic function, is dependent on age, heart rate, and loading conditions.[17]

Tei index is a favorable tool for that aim, which is a doppler-derived time interval index that estimates both systolic and diastolic cardiac performance. The Tei index is simple, noninvasive, easy to assess reproducible, and independent of age, heart rate, and loading condition when a patient is supine.[16] It assesses independently the myocardial performance of the left and right ventricles.[418]

The Tei index is considerably affected by the severity of CAD.[19] Because of the importance of the systolic parameters that contribute to the Tei index, such as IVCT and ET. Thus, the index maintains a strong inverse relation with EF: the higher the value of the index, the lower the EF and vice versa. Tei index has a close association with diastolic hemodynamic indices and appears superior to conventional diastolic parameters in the detection of impaired relaxation.[4]

Biventricular estimation of the index improves the prognostic precision of the LV Tei index significantly. Due to the close relation of both ventricles, as well as the sharing of interventricular septum and pericardium, it seems that LV disorders are transported to the RV, and overall evaluation of cardiac function appears more precise in identification of any problem than LV assessment alone. A value of the index ≥0.60 (patients at increased risk) has the maximum sensitivity, specificity, and diagnostic accuracy in the identification of patients with adverse endpoints, more superior than EF ≤40%.[16]

Since Tei index has been studied in several cardiac disorders including heart failure, myocardial infarction, hypertension and diabetes mellitus and verified its efficacy to predict both worsened morbidity and mortality outcomes. Therefore, we tried in this work to examine the capability of Tei index to predict the severity of CAD (as assessed by the SS) in patients with CCS and normal LV systolic function which could be of a paramount value in risk stratifying these patients which might give a better guide for the best line of management for such patients whether conservative or invasive approach.[5] Therefore, we tried in this work to examine the capability of Tei index to predict the severity of CAD (as assessed by the SS) in patients with CCS and normal LV systolic function which could be of a paramount value in risk stratifying these patients which might give a better guide for the best line of management for such patients whether conservative or invasive approach.

As regards the echo parameters, in our studied group, the mean values of IVRT were higher than the standard normal values (127.94 ± 28.64), while ET was decreased in the presence of LAD affection and/or more than two-vessel affection which is concordant with the studies done by Tei et al., Milzman and Dubin, and Henkel et al., who emphasized that myocardial ischemia, especially due to LAD and/or more than two-vessel affection, causes impairment of myocardial performance even though the EF is apparently normal. This is attributed to the altered myocardial mechanics, decrease in ET, and increase in IVCT and IVRT causing impairment in myocardial performance.[82021]

In our work, the IVRT values were abnormal in all patients which denotes that IVRT is a diastolic parameter which is more affected in myocardial ischemia than do other diastolic parameters. This concept is concordant with a study that was done to assess the LV diastolic function following angioplasty of an infarct-related artery. It showed that the IVRT duration was shortened after revascularization (103 ± 21 ms vs. 87 ± 20 ms, P < 0.001).[17]

Another study showed that IVRT prolongation was associated with greater odds of CAD, while its shortening was associated with lower odds of CAD (all P ≤ 0.001).[18]

Moreover, in the current study, there was a positive correlation between IVRT and SS (r = 0.39, P < 0.01). These results were concordant with the study that was done by Ammar et al., who showed the IVRT mean values correlated significantly with SS (P = 0.005).[22]

As regards E/A ratio, it was abnormal in only 55% of patients (53% with ratio ≤0.8, 2% with ratio >2) with a negative correlation with SS (r = −0.04, P = 0.65) which came in line with the study done by Milzman D et al. which showed a negative relation between the severity of the disease as presented by SS and Gensini score and LV diastolic function as evidenced by E/A ratio.[20] Moreover, another study that assessed mitral inflow velocity (E/A) declared that there was an overall significant difference in the SS between normal, Grade 1, Grade 2, and Grade 3 diastolic dysfunction (P < 0.0001).[20]

In our work, echo measurements showed that there was a positive correlation between SS and E/E' (r = 0.20, P = 0.04). A study was done to assess LV diastolic dysfunction parameters as an indication for the severity of CAD which showed similar results to ours as it declared a significant positive correlation between SS and E/E'.[20]

As regards the coronary anatomy, in our study, the studied patients were subdivided according to the number of affected vessels into three groups. There were statistically significant differences between all of these groups as regards the Tei index with greater mean values in the group of more than two-vessel disease. The mean values of Tei index in intermediate SS group were higher than that of low SS group (0.89 ± 0.22, 0.81 ± 0.22), respectively.

Furthermore, there was a positive correlation between SS and Tei index (r = 0.495, P < 0.01). Similarly, multiple studies done by Tei et al., Milzman and Dubin, and Henkel et al. showed similar results to ours, as the mean values of Tei index were higher than the standard normal values in the presence of LAD affection and/or more than two-vessel affection.[82021]

Our results were concordant with a study done by Valgimigli et al., who evaluated 106 patients who were presented with typical chest pain, had positive stress tests, and showed more than 50% stenosis in at least one vessel in their CA. There was a significant positive correlation between SS and Tei index (r = 0.44. P < 0.01).[23]

In addition, another study done by Sahin et al., who agreed to our results, included 106 patients with obstructive stable CAD and 30 patients with nonobstructive CAD (determined by CA). The patients were categorized into three groups according to their SS (low, intermediate, and high). Tei index of high syntax group was more than that of intermediate and low groups with mean values of 0.90 ± 0.2, 0.84 ± 0.3, and 0.65 ± 0.3, respectively. There was a significant positive correlation between SS and Tei index (r = 0.564, P < 0.001).[24]

Another study that was done by Ammar et al. showed that when patients were classified into three groups with low, mid, and high SS, it was obvious that the mean Tei index increased significantly from low to high scores (low 48.41 ± 4.07, mid 51.81 ± 4.39, high 55.56 ± 3.99, with (P < 0.001). Furthermore, there were significant positive correlations between Tei index with the SS (r = 0.718, P < 0.001) and the number of diseased vessels (r = 0.634, P < 0.001).[22]

CONCLUSION

Tei index is a unique noninvasive modality for predicting the severity of CAD (as reflected by SS) in patients with CCS which could be of fruitful value by risk stratifying them and which may add an essential parameter for anticipation of whom are more vulnerable for the future cardiovascular events, therefore applying more invasive procedures for them.

Limitations

Relatively small study sample size, especially when considering the patients' subgroups: LAD, non-LAD, one, two, and more than two vessels

Study did not include patients with high SS

It is not a controlled study.

Recommendations

Further studies are needed to assess the correlation between the Tei index and SS on a larger number of CCS patients and including patients with high SS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.