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Correlation of the Tei Index With Left Ventricular Dilatation and Mortality in Patients With Acute Myocardial Infarction Isil ¸ UZUNHASAN,1 MD, Khalid BADER,1 MD, Bans¸ OKÇUN,1 MD, MUTLU,1 MD Ali Can HATEMI,1 MD, and Hasim ¸ SUMMARY The Tei index is an echocardiographic index of combined systolic and diastolic function, calculated as isovolumetric relaxation time plus isovolumetric contraction time divided by ejection time. The aim of this study was to define the correlation of the Tei index with left ventricular dilatation and mortality in patients with acute myocardial infarction (AMI). A total of 77 patients (58 men, 19 women) with a mean age of 53 ± 12 years, who had presented with an AMI in our clinic between June 2001 and February 2002 were compared with a control group of 88 healthy subjects (63 men, 25 women) with a mean age of 55 ± 6 years. Echocardiographic evaluation was carried out within 24 hours and the third month of AMI, using a 3.5 MHz probe with pulse wave Doppler recordings by the adult cardiac mode of an Acuson C 256 echocardiograph. There were statistically significant differences between the 2 groups in all echocardiographic parameters, except mitral A wave. Thirteen patients died during the follow-up period of 3 months. The Tei index was significantly higher in the patients who died compared with those who survived (0.70 ± 0.10 versus 0.61 ± 0.10; P < 0.001). The patients who had heart failure after AMI had a mean Tei index value of 0.76 ± 0.27, whereas the patients who did not have heart failure after AMI had a significantly lower Tei index value of 0.60 ± 0.32 (P < 0.05). Patients were divided into 2 groups according to their Tei index. Patients with a > 0.60 Tei index had significantly higher end-systolic and enddiastolic volumes compared to patients with a < 0.60 Tei index (P < 0.001 for both) in the acute phase of AMI. Within 3 months, patients with a Tei index < 0.60 had a significant reduction in end-diastolic volumes (P < 0.01), whereas the end-diastolic volumes did not change significantly in patients with an index > 0.60 (P = 0.19). The Tei index is an important indicator of left ventricular dysfunction and death after AMI. A greater Tei index at the onset of AMI is associated with a higher incidence of subsequent cardiac death, CHF, and progressive LV remodeling. (Int Heart J 2006; 47: 331-342) Key words: Tei index, Acute myocardial infarction, Mortality, Left ventricular dysfunction From the 1 Department of Cardiology, Medical Faculty, Istanbul University, Istanbul, Turkey. Address for correspondence: Uzunhasan Isil, ¸ MD, Department of Cardiology, Medical Faculty, Istanbul University, Ataköy 9. Klslm B-6 Blok Daire 58 Baklrköy, Istanbul, Turkey. Received for publication November 14, 2005. Revised and accepted February 16, 2006. 331 332 UZUNHASAN, ET AL Int Heart J May 2006 MYOCARDIAL remodeling after acute myocardial infarction (AMI) is a process of progressive left ventricular (LV) dilation that contributes to the development of cardiac failure and late mortality.1) AMI results in both left ventricular systolic and diastolic dysfunction, which have independent prognostic value.2,3) Doppler echocardiography is a rapid, feasible, and simple noninvasive method of assessing the prognostic factors in AMI. Clinical data demonstrate that Doppler echocardiography provides important information about left ventricular diastolic function and early dilatation after infarction in AMI patients.1,4,5) In recent years, some researchers have been working on a new diagnostic method besides EF. This new method, known as the Tei method or myocardial performance index (MPI), was first defined by Chuwa TEI and is still at the stage of research.6) This index is used to evaluate both the systolic and diastolic functions of the ventricle.7) In this study, we evaluated the predictive value of this new index on the clinical parameters of mortality, CHF, and left ventricular dilatation in patients with acute myocardial infarction. METHODS We prospectively studied 77 consecutive patients (58 men, 19 women; mean age, 53.7 years) with a diagnosis of transmural first MI referred to the intensive care unit of Istanbul University Institution of Cardiology between June 2001 and February 2002. AMI was diagnosed on the basis of a combination of typical anginal pain of at least 30 minutes in duration, diagnostic serial electrocardiographic changes consisting of new pathological Q waves with or without ST and T wave changes and a typical rise and fall in the concentration of serum total creatine kinase or creatine kinase MB. Exclusion criteria included the presence of atrial fibrillation, a permanent pacemaker, dementia, aortic stenosis, inappropriate Doppler recordings, and chronic obstructive lung disease. Normal values of time intervals in the Doppler indexes were assessed in 88 healthy volunteers (63 men, 25 women; mean age, 55.8 years) with no history of cardiovascular diseases and normal results on electrocardiography and 2-dimensional and Doppler echocardiography. The mean age of the control group was 55.8 ± 6.9 years. All patients with AMI were given standard aspirin, β-blockers, nitrates, ACE inhibitors, and thrombolytic treatment. The protocol was approved by the regional scientific ethical committee, and all enrolled patients gave written, informed consent. Echocardiography was performed within 24 hours of arrival at the coronary care unit using an Acuson C256 echocardiography system with a 3.5-MHz transducer, and repeated after 90 days in all surviving patients. Vol 47 No 3 TEI INDEX IN ACUTE MYOCARDIAL INFARCTION 333 Figure 1. Measurement of Tei index. Mitral inflow was recorded with the transducer in the apical 4-chamber view. The pulsed wave Doppler beam was aligned as perpendicular as possible to the plane of the mitral annulus. The Doppler sample volume was placed between the tips of the mitral leaflets during diastole. The LV outflow velocity curve was recorded from the apical long-axis view with the Doppler sample volume positioned just below the aortic valve. Time intervals for calculating the myocardial performance index (Tei index) were measured from mitral inflow and LV outflow recordings, as illustrated in Figure 1. Three consecutive beats were measured and averaged for each Doppler variable. Left ventricular ejection fraction (EF) was estimated by the Simpson method using apical 4-chamber views of left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) values. The echocardiographic parameters of the subgroups of AMI patients who died and survived, and patients who had clinical heart failure with those who had not were compared. Patients also were divided into 2 groups according to their Tei index value (< or > 0.60) and compared by echocardiographic and critical analysis. Statistical analysis: The data were analyzed statistically by Epi-Info 2000 software program using the Student t-test, paired t-test, Mann-Whitney U test, chi- 334 Int Heart J May 2006 UZUNHASAN, ET AL square, Fisher exact chi-square test, and/or Pearson correlation analysis test. The level of statistical significance was defined as a P value less than 0.05. RESULTS A total of 77 AMI patients (58 males, 19 females; mean age, 53.7 ± 12.0 years) and 88 healthy subjects (63 males, 25 females; mean age, 55.8 ± 6.9 years) Table I. Distribution of Patients and Healthy Control Group According to Sociodemographic Variables and Risk Factors Male Age (years) Height (cm) Weight (kg) BMI (kg/m2) Family history of AMI Hypertension Diabetes mellitus Smoking Anterior MI Inferior MI Q-Wave MI Patients with AMI (n = 77) Healthy control group (n = 88) 58 (75.3%) 53.7 ± 12.0 167.0 ± 7.3 75.3 ± 10.4 27.0 ± 3.5 12 (15.6%) 36 (46.8%) 25 (32.5%) 53 (68.8%) 41 (53.2%) 27 (35.0%) 68 (88.3%) 30 (34.1%) 55.8 ± 6.9 164.2 ± 8.5 67.9 ± 11.1 25.2 ± 3.8 3 (3.4%) 28 (31.8%) - P 0.001 0.18 0.02 0.001 0.001 0.007 0.001 0.001 0.001 Values are given as n (%) or mean ± standard deviation. BMI indicates body mass index; AMI, acute myocardial infarction; and MI, myocardial infarction. Table II. Echocardiographic Parameters of Patients and Healthy Control Group Echocardiographic parameter LVDD (cm) LVSD (cm) LVEDV (cm3) LVESV (cm3) EF (%) Mitral E wave (cm/sec) Mitral A wave (cm/sec) Deceleration time for E wave (msec) IRT (msec) ICT (msec) ET (msec) Tei index Patients with AMI (n = 77) Healthy control group (n = 88) P 5.1 ± 0.5 3.5 ± 0.7 123.0 ± 23.7 69.1 ± 23.0 44.1 ± 9.0 0.6 ± 0.2 0.6 ± 0.1 162.5 ± 0.4 78.4 ± 9.9 76.1 ± 16.6 252.6 ± 35.5 0.63 ± 0.1 4.7 ± 0.4 2.8 ± 0.5 101.3 ± 22.4 35.9 ± 11.0 69.2 ± 6.9 0.9 ± 0.2 0.7 ± 0.4 196.1 ± 32.2 83.4 ± 9.9 43.9 ± 11.0 326.1 ± 21.0 0.39 ± 0.03 0.001 0.001 0.001 0.001 0.001 0.001 0.589 0.001 0.002 0.001 0.001 0.001 Values are given as mean ± standard deviation. LVDD indicates left ventricular diastolic diameter; LVSD, left ventricular systolic diameter; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular endsystolic volume; EF, ejection fraction; IRT, isovolumetric relaxation time; ICT, isovolumetric contraction time; and ET, ejection time. Vol 47 No 3 335 TEI INDEX IN ACUTE MYOCARDIAL INFARCTION were included in the study. The distribution of subjects in the study groups according to sociodemographic variables and risk factors for AMI is presented in Table I. The frequencies of risk factors for AMI regarding age, gender, history of diabetes mellitus, history of hypertension, serum cholesterol, and smoking status were found to be significantly higher in the patient group, as expected. The echocardiographic parameters of ejection fraction (EF), deceleration time for E wave, isovolumetric relaxation time (IRT), and ejection time (ET) were significantly lower and isovolumetric contraction time (ICT) was significantly longer in the patient group compared with the healthy group of individuals (P < 0.001) (Table II). The Tei index was also significantly higher in the patient group (0.63 ± 0.10 versus 0.39 ± 0.03) compared with the healthy control group (P < 0.001) (Table II). During the 3 month follow-up period of the 77 patients with AMI, 13 Table III. Echocardiographic Parameters of Surviving Versus Dead Patients Tei index IRT (ms) ICT (ms) ET (ms) EF (%) LVEDV (cm3) LVESV (cm3) Age Mitral E wave/Mitral A wave DT for E wave (ms) DT for A wave (ms) Surviving patients Dead patients P 0.61 ± 0.1 79.2 ± 9.6 73.3 ± 14.8 258.9 ± 33.6 46.5 ± 7.3 119.0 ± 17.8 63.6 ± 14.7 51.5 ± 11.3 0.9 ± 0.3 132.2 ± 28.4 54.7 ± 12.5 0.7 ± 0.1 74.5 ± 10.6 90.2 ± 18.6 221.6 ± 28.2 32.3 ± 7.6 142.9 ± 36.9 95.7 ± 36.0 64.4 ± 9.9 0.7 ± 0.3 168.7 ± 30.2 58.0 ± 10.2 0.001 0.10 0.001 0.001 0.001 0.004 0.001 0.001 0.02 0.001 0.10 Values are given as mean ± standard deviation. IRT indicates isovolumetric relaxation time; ICT, isovolumetric contraction time; ET, ejection time; EF, ejection fraction; LVEDV, left ventricular enddiastolic volume; LVESV, left ventricular end-systolic volume; and DT, deceleration time. Table IV. Left Ventricular End-diastolic and End-systolic Volume for Patients With a Tei Index > 0.60 and < 0.60 Taken in the Acute Phase of MI and 3 Months Later Tei index > 0.60 (n = 27) Tei index < 0.60 (n = 37) LVEDV (cm ) LVESV (cm3) LVEDV (cm3) LVESV (cm3) 3 Initial 3 months later P 122.7 ± 21.5 70.7 ± 16.3 116.3 ± 14.3 58.5 ± 11.0 161.5 ± 16.6 92.3 ± 17.0 113.0 ± 20.9 53.3 ± 15.2 0.001 0.001 0.19 0.01 Values are given as mean ± standard deviation. LVEDV indicates left ventricular end-diastolic volume and LVESV, left ventricular end-systolic volume. 336 UZUNHASAN, ET AL Int Heart J May 2006 (16.6%) patients died due to sudden cardiac death, 22 (28.5%) patients developed CHF (Killip V > II or NYHA > grade II), 2 patients developed reinfarction, and 34 patients underwent revascularization procedures. When the echocardiographic parameters of survival versus death and CHF positive versus negative patients were compared, a high Tei index, short ejection time, low EF, increased age (not for heart failure), and increased left ventricular diastolic and systolic diameter were defined as risk factors for mortality and CHF (Tables III, IV). Figure 2. Comparison of the mortality rates in patients with a Tei index > 0.60 and < 0.60. Figure 3. Comparison of the incidence of heart failure in patients with a Tei index > 0.60 and < 0.60. Vol 47 No 3 TEI INDEX IN ACUTE MYOCARDIAL INFARCTION 337 Figure 4. Comparison of incidences of Tei index > 0.60 and < 0.60 in patients with inferior and anterior MI. The mortality and heart failure rate in patients with a Tei index > 0.60 and < 0.60 were compared. In the high Tei index (> 0.60) group, 12 patients died (30.8%) and 19 developed heart failure (48.7%), while in the low Tei index (< 0.60) group only one patient died (2.6%) and 3 (7.9%) developed heart failure (P = 0.001 for both) (Figures 2 and 3). When anterior and inferior infarctions were compared regarding the Tei index values, in patients with anterior infarction, the ratio of patients with a Tei index > 0.60 was higher (63.4%) than patients with inferior infarctions (29.7%) (P = 0.001) (Figure 4). For patients with a Tei index > 0.60, both LVEDV and LVESV increased significantly at the end of 3 months. On the other hand, for patients with a Tei index < 0.60, LVESV decreased significantly and LVEDV did not change. DISCUSSION In this study, we evaluated the correlations between MPI, also called the Tei index, with left ventricular dilatation, CHF, and cardiac mortality rates following AMI. We concluded from the results that the echocardiographic parameters of patients with AMI were significantly different from those of the healthy group of individuals. The Tei index was also significantly higher in the patient group compared with the healthy control group. A high Tei index (> 0.60), short ejection time, low EF, increased age, and increased left ventricular diastolic and systolic 338 UZUNHASAN, ET AL Int Heart J May 2006 diameter were defined as risk factors for mortality and CHF. We first compared the echocardiographic parameters of patients who recently had AMI and parameters of a healthy group in this study. As expected, the EF, deceleration time for E wave, IRT, and ET were found to be significantly lower whereas ICT was significantly longer in patients with myocardial infarction compared with healthy individuals. In accordance with these results, the Tei index and both systolic and diastolic left ventricular diameters were higher in patients with myocardial infarction compared with the healthy control group. AMI is characterized by loss of contractile tissue and changes of ventricular geometry.8,9) The life expectancy of the AMI patient greatly depends on protection of the remaining contractile elements, and the maintenance of the optimum function of these elements. Ischemia changes the myocardial activity periods of isovolumetric contraction and relaxation. Due to ischemic cascade, ICT and IRT increase, and when clinical heart failure becomes apparent, the ET decreases.10) Previously EF was used to evaluate the patients' condition in these cases. However, this traditional risk stratification of AMI patients is focused only on systolic function, in which numerous studies have demonstrated that EF or other parameters are powerful guides to choosing therapy and predicting the risk of future events.2,11,12) Because systolic and diastolic dysfunctions frequently coexist, a combined measure of left ventricular chamber performance may be more reflective of overall cardiac dysfunction than systolic or diastolic measures alone. A more complete study of ventricular function would be useful to further understand the disease development after AMI. Tei, et al studied the ability of a new Doppler index of combined systolic and diastolic function (Tei index: sum of IRT and ICT divided by ET) to separate patients with normal ventricular function from patients with heart failure nearly a decade ago.6) They showed that the separation of patients with dilated cardiomyopathy from normal individuals, by use of the Tei index, was superior to other available indexes. Other studies have described the prognostic value of the Tei index after AMI.13,14) The Tei index has been shown to be a powerful independent predictor of death from all causes in a large population with a recent AMI. Adverse outcome is infrequently seen among patients with preserved global ventricular function (Tei index < 0.46).15) Furthermore, the Tei index has the advantages of being less affected by age, heart rate, and preload than conventional Doppler measurements,16-18) and the index has an excellent reproducibility.6,13,19,20) The Tei index is found to be very reliable and has a predictor role not only in MI, but also in other cardiac pathologies such as dilated cardiomyopathy, primary pulmonary hypertension, cardiac amyloidosis, and aortic stenosis as well.21-23) Vol 47 No 3 TEI INDEX IN ACUTE MYOCARDIAL INFARCTION 339 Thirteen of 77 in our patient group died and 22 had CHF. The mean value of the Tei index was significantly higher when we compared the Tei index of dead patients with surviving ones and patients who have CHF with patients who do not have CHF. This finding suggests that the Tei index may be used as a predictor of mortality and CHF. In accordance with our findings, it was previously shown that the one year life expectancy of AMI patients is higher (89%) in patients who had smaller Tei index values. Unfortunately, the life expectancy of patients with a high Tei index was only 37%.13) After 3 months of follow-up we found that the Tei index of 12 of the 13 patients who died was higher than 0.60. The mortality risk for patients with a lower Tei index was only 2.6%, while it was 30.8% for the higher group. Moreover, in patients with a higher Tei index the incidence of CHF was higher than the patients with low Tei index values.14) We classified our patient group according to Tei indexes below 0.60 or above 0.60. Nearly half of the Tei index > 0.60 group developed CHF, but only 7.9% of the Tei < 0.60 group developed CHF, in accordance with other studies,14) which also supports the suggestion that the Tei index might be useful for predicting morbidity rates in AMI. The Tei index has been shown to be significantly different between CHF and healthy groups too, and the authors suggested that the Tei index might be useful for evaluating cardiac dysfunction.15) Based on these findings, it would not be wrong to suggest that the Tei index is an important predictor of mortality and CHF risk after AMI. It was previously shown that the Tei index is negatively correlated with EF, but positively correlated with the prognosis.24) Our findings also support this, as the mean EF of the patients who died was significantly lower than the EF of the surviving patients. On the other hand, the Tei index was higher in the patients who died compared with those who survived. Ventricular remodeling or dilatation is an alteration in the shape, mass, and volume of the left ventricle, a process which develops in response to myocardial injury and/or changes in the preload and afterload. Ventricular remodeling is a defective adaptation process. The extent of ventricular remodeling is a very strong indicator of mortality and morbidity in patients with cardiac failure or MI. Ventricular remodeling is positively correlated with the infarct size,25) and it develops in several days.25,26) On the other hand, progressive left ventricular dilatation may continue for months or years.25,27) The continuous expansion in the left ventricle after AMI is a negative prognostic sign.28) LVESV is known to be a very strong predictor of life expectancy, morbidity and mortality after AMI, coronary artery disease, and ischemic cardiomyopathy.2,11,29-31) In this study, left ventricle volumes were measured within 24 hours and 3 months after AMI. Initial left ventricle volumes were significantly higher than the 340 UZUNHASAN, ET AL Int Heart J May 2006 healthy control group, and they were still high in the 3rd month measurements as well. We also showed that the left ventricle volumes of patients who died were significantly higher than the left ventricle volumes of the surviving patients, which is in agreement with previous findings. Left ventricle volumes were all high in patients who developed cardiac failure. In AMI patients, short E deceleration time,32) age, anterior MI, initial left ventricle volumes, volume of the infarct, left ventricular end-diastolic pressure, and mitral valve failure are strong predictors of possible left ventricular dilatation.33) We also evaluated if the Tei index may be a predictor of ventricular remodeling, and found that patients with a high Tei index were more prone to develop ventricular dilatation in this study. We suggest that the initial Tei index may be a strong indicator of ventricular dilatation risk in AMI patients. Thus, the prognostic value of the Tei index is very important as it will help to identify patients with high risk of ventricular remodeling sooner and the undertaking of precautions to prevent progressive remodeling. In this study, we also showed that the patients with anterior AMI had a higher Tei index than the patients with inferior AMI in accordance with previous studies.15,34) The loss of contractile function in anterior infarcts is more extensive compared with inferior infarcts. Thus, myocardial damage of equal size affects EF to a greater degree in the anterior than in the inferior wall.35) This could partly explain the additional prognostic value of the Tei index. In this study, we have showed that the Tei index, ICT, ET, EF, LVESV and LVEDV, mitral valve E/A proportion, and E deceleration time are the echocardiographic parameters that are the most important indicators of the mortality due to AMI. 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