Recently proposed Tei index, 1 defined as the sum

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1 Effects of Valve Dysfunction on Doppler Tei Index Amdadul Haque, MBBS, Yutaka Otsuji, MD, Shiro Yoshifuku, MD, Toshiro Kumanohoso, MD, Hui Zhang, MD, Akira Kisanuki, MD, Shinichi Minagoe, MD, Ryuzo Sakata, MD, Chuwa Tei, MD, Kagoshima, Japan Background: Recently proposed Doppler Tei index, defined as the sum of isovolumic contraction time or mitral valve closure to aortic valve opening time and isovolumic relaxation time or aortic valve closure to mitral valve opening time divided by ejection time, is a simple measure which enables noninvasive estimation of combined systolic and diastolic function and prediction of patients prognosis. However, effects of valve dysfunction on Tei index have not been investigated. This study was designed to compare Tei index before and after surgical valve replacement or repair to evaluate effects of valve dysfunction on Tei index. Methods: Participants consisted of 76 consecutive patients with aortic or mitral valve surgery (26 patients with aortic stenosis [AS], 16 with aortic regurgitation, 17 with mitral stenosis, and 17 with mitral regurgitation). Doppler Tei index was evaluated before and after the surgery by obtaining (a b)/b, where a is the interval between the cessation and onset of Doppler mitral filling flow and b is the aortic flow ejection time. Results: Tei index significantly increased after surgery in patients with AS ( to , P <.001), aortic regurgitation ( to , P <.01), mitral stenosis ( to , P <.01), and decreased with no significance in mitral regurgitation ( to ). Percent change in Tei index after valve surgery was maximal in patients with AS (27 6vs17 2vs 16 6vs 9% 6%, AS vs aortic regurgitation vs mitral stenosis vs mitral regurgitation, P <.001). Conclusion: Tei index significantly changes after valve surgery especially in patients with AS. Considerations for the effects of valve dysfunction on Tei index are required for its application to evaluate ventricular function in patients with valve disease. (J Am Soc Echocardiogr 2002;15: ) Recently proposed Tei index, 1 defined as the sum of isovolumic contraction time (ICT) or mitral valve (MV) closure to aortic valve (AV) opening time and isovolumic relaxation time (IRT) or AV closure to MV opening time divided by ejection time (ET), has been reported to be a good index expressing global cardiac function predicting patients prognosis Tei index uses systolic and diastolic cardiac time intervals which are known to be influenced by valvular diseases However, effects of valvular diseases on Tei index has not been investigated. We, therefore, compared Tei index in patients with aortic or MV disease before and after surgical replacement or repair to evaluate effects of valvular diseases on Tei index. From the First Department of Internal Medicine, and Second Department of Surgery (R.S.), Kagoshima University School of Medicine. Reprint requests: Yutaka Otsuji, MD, First Department of Internal Medicine, Kagoshima University School of Medicine, Sakuragaoka, Kagoshima City, , Japan ( yutaka@m.kufm.kagoshima-u.ac.jp). Copyright 2002 by the American Society of Echocardiography /2002/$ /1/ doi: /mje METHODS Study Participants Seventy-six consecutive patients who underwent surgical valve replacement or repair were enrolled in the study. There were 42 men and 34 women. Their age ranged from 32 to 76 years old with a mean age of 55 7 years old. Seven patients with combined valvular diseases such as significant aortic stenosis (AS) in addition to important mitral regurgitation (MR) were excluded. Consequently, 69 patients including 22 with AS, 14 with aortic regurgitation (AR), 17 with mitral stenosis (MS), and 16 with MR comprised the study participants. The control group consisted of 30 participants with no known cardiovascular disease and an echocardiogram with normal findings. Surgery was performed successfully in all the patients and there were no significant changes in heart rate or blood pressure after the surgery (Table 1). All patients gave their informed consent and the Institutional Committee on Human Research of Kagoshima University Hospital also approved the study protocol. Doppler Echocardiography Standard 2-dimensional and Doppler echocardiographic examinations were performed with commercially available equipment (SSH 380A, Toshiba, Tokyo, Japan; 5500, 877

2 878 Haque et al September 2002 Table 1 Changes in heart rate and blood pressure after valve surgery AS AR MS MR HR SBP HR SBP HR SBP HR SBP Before surgery After surgery AS, Aortic stenosis; AR, aortic regurgitation; MS, mitral stenosis; MR, mitral regurgitation; HR, heart rate; SBP, systolic blood pressure. Table 2 Changes in left ventricular and left atrial dimensions after valve surgery Group Before surgery After surgery P value Figure 1 Scheme to measure Tei index simply from 2 time intervals by pulsed Doppler mitral and aortic flow velocity. Interval a: from cessation to next onset of mitral flow; interval b: from onset to cessation of aortic flow. Tei index can simply be calculated as (a b)/b. To obtain ICT and IRT, we added measurements of intervals c and d. Interval c: from peak QRS to onset of mitral flow; interval d: from peak QRS to cessation of aortic flow. Interval c d IRT. ICT can then be calculated as (a b) (c d). ICT, Isovolumic contraction time; IRT, isovolumic relaxation time; ET, ejection time. Aloka, Tokyo, Japan; HDI 3000 and 5000, Advanced Technology Laboratories, Bothell, Wash; Sonos 5500, Agilent Technologies, Andover, Mass) with 2 to 3 MHz transducers. The mitral inflow velocity was recorded from the apical 4-chamber view with Doppler sample volume placed at the tips of the mitral leaflets during diastole. The left ventricular (LV) outflow velocity was recorded from the apical long-axis view with the sample volume just below the AV. All sample volumes were positioned with ultrasonic beam alignment to flow. Doppler tracings were recorded at a paper speed of 50 or 100 mm/s. Echocardiographic examinations were performed in all the patients 5 to 30 days before surgery and were repeated 7 to 30 days after the surgery. All images were recorded on VHS videotapes for analysis. LV end-diastolic and end-systolic cavity areas were traced in the apical 4- and 2-chamber views, and LV volumes and the ejection fraction were obtained using the modified biplane Simpson s method. 21 End-diastolic and end-systolic frames were determined as the initial and last frame with systolic mitral leaflet closure, respectively. AS LVDd LVDs NS %FS NS LAD NS AR LVDd LVDs NS %FS LAD NS MS LVDd NS LVDs NS %FS NS LAD NS MR LVDd LVDs NS %FS LAD AS, Aortic stenosis; LVDd, left ventricular end-diastolic dimension; LVDs, left ventricular end-systolic dimension; FS, fractional shortening; LAD, left atrial dimension; AR, aortic regurgitation; MS, mitral stenosis; MR, mitral regurgitation; NS, not significant. Flow velocities through stenotic lesions were evaluated by continuous wave Doppler echocardiography and valvular regurgitation was evaluated by standard color flow Doppler. Measurements of the time intervals on the Doppler recordings were conducted using an offline commercial digitizing system (Freeland systems analyzer, Tomtec Imaging, Boulder, Colo). Five consecutive beats were measured and the values were averaged. The following Doppler time intervals were measured from mitral and aortic flow velocity profiles. 1,2 The interval a, from cessation to onset of mitral inflow, is equal to the sum of the ICT, ET, and IRT (Figure 1). The interval b, ET, was measured as the duration of ventricular ejection flow. Thus, the sum of the ICT and IRT was obtained by subtracting interval b from interval a. The Doppler-derived Tei index, combining systolic and diastolic function, was then calculated as (a b)/b (Figure 1). In addition, IRT was obtained by subtracting interval d, between the peak QRS of the ECG and the cessation of LV outflow ejection, from interval c, between the peak QRS and the onset of mitral inflow. The ICT was also obtained by subtracting the IRT from (a b) (Figure 1). In patients with AR and MR, there is no clear

3 Volume 15 Number 9 Haque et al 879 Figure 2 Changes in cardiac time intervals by valve surgery in aortic stenosis. ICT, Isovolumic contraction time; IRT, isovolumic relaxation time; ET, ejection time; *P.05; **P.01; ***P.001. ICT and IRT. In those patients, the time interval from MV closure to AV opening and the interval from AV closure to MV opening are more appropriate terms rather than ICT and IRT. However, we used ICT and IRT even to these patients to simplify terminology. Statistical Analysis Continuous numerous variables are expressed as mean value SD. Differences in variables before and after surgery were assessed by paired Student t test. A P value.05 was considered significant. RESULTS Figure 3 Scattergraph showing peak aortic flow velocity before surgery versus change in Tei index after surgery. There was good correlation between peak aortic flow velocity before surgery and change in Tei index. Changes in LV and Left Atrial Dimensions After Valve Surgery Table 2 summarizes changes in LV dimension, its percentage of fractional shortening, and left atrial dimension after valve surgery in the 4 groups. AS Figures 2 and 3 show ICT before and after surgery had normal values and showed no difference compared with control participants. IRT before surgery was significantly longer compared with control patients (P.05) and did not change after surgery. ET was also significantly prolonged before surgery compared with control patients (P.001). However, the prolongation of ET disappeared after surgery and it was even shorter than normal values (P.001). Consequently, Tei index was of normal value before surgery. However, it was significantly increased after surgery (P.001). Changes in Tei index after surgery significantly correlated with peak aortic flow velocity before the surgery (Figure 3). AR Figure 4 shows ICT before surgery was significantly longer compared with control patients (P.001)

4 880 Haque et al September 2002 Figure 4 Changes in cardiac time intervals by surgery in aortic regurgitation. ICT, Isovolumic contraction time; IRT, isovolumic relaxation time; ET, ejection time; *P.05; **P.01; ***P.001. Figure 5 Changes in cardiac time intervals by surgery in mitral stenosis. ICT, Isovolumic contraction time; IRT, isovolumic relaxation time; ET, ejection time; *P.05; **P.01; ***P.001. and the ICT did not significantly change after surgery. IRT before surgery was also significantly increased (P.001) and did not change after surgery. ET before surgery was significantly shorter compared with control participants (P.001). After surgery, further significant shortening in ET was observed (P.05). Consequently, Tei index before surgery was significantly increased compared with

5 Volume 15 Number 9 Haque et al 881 control patients (P.001). After surgery, a further increase in Tei index was observed (P.01). MS Figure 5 shows ICT, IRT, and ET were significantly shorter before surgery compared with control patients. These time intervals similarly significantly increased after surgery. As a result, Tei index in patients with MS was significantly decreased before surgery (P.001) and it increased to normal value after surgery (P.01). MR In Figure 6, ICT and IRT were of normal value before and after surgery. ET before surgery was significantly shorter compared with control patients (P.001). The ET increased but with no significance after surgery. As a result, Tei index before surgery was significantly larger compared with control patients (P.001) and decreased but with no significance after surgery. DISCUSSION Changes by Surgery in AS It has already been shown that ET and IRT are prolonged whereas ICT remains of normal value in patients with AS, 13,14,16-18,20,22-33 and these are explained as impedance to LV ejection and LV impaired relaxation with hypertrophy. Results of the current study are consistent with these previous investigations. Consequently, Tei index before surgery was of normal value. After surgery significant shortening of ET was observed without change in IRT. These results seem reasonable, because prolongation of ET by increased resistance to LV ejection can be corrected by surgery and longer IRT by impaired LV relaxation caused by hypertrophy may last after surgery. 14,16-18 Consequently, Tei index significantly increased after surgery, demonstrating that Tei index can be underestimated in the presence of AS. Changes by Surgery in AR It has already been shown that ET and IRT are prolonged whereas ICT is of normal value in patients with AR, 13,16,17,25,26,29,30,34,35 and these are explained as being a result of increased LV ejection volume, AR during IRT slowing down LV pressure fall, and LV impaired relaxation because of hypertrophy. In our study ICT was longer and ET was shorter compared with control participants. In the current study, multiple patients with AR also had LV dysfunction, shown as increased LV systolic dimension (Table 2). Longer ICT in the current study can be explained by addition of LV dysfunction. Regarding shortened ET, AR causes longer ET and LV dysfunction causes shorter ET. We therefore speculate that effects of LV dysfunction were dominant compared with effects of AR. Consequently, Tei index before surgery was significantly increased. After surgery, significant further shortening of ET was observed without change in ICT and IRT. Correction of AR is expected to cause reduction in ET and also in IRT. As described previously, many patients with AR had additional LV dysfunction resulting in congestive heart failure. We therefore speculate that reduction in left atrial pressure after surgery may prolong IRT and cancel out effects by correction of AR to shorten IRT. Consequently, after surgery a further increase in Tei index was observed. Changes by Surgery in MS It has already been shown that ICT, ET, and IRT are shortened in patients with MS, 15,17,18,22 and these are explained as results from low aortic pressure, high left atrial pressure, and reduced stroke volume. Results of this study were consistent with these previous investigations. Consequently, Tei index before surgery was decreased. As expected, significant increases in ICT, ET, and IRT were observed after surgery. As a result, Tei index increased to a normal value after surgery. Changes by Surgery in MR It has already been shown that ET is shortened whereas ICT and IRT remain of normal value in patients with MR 17,19,36 and this is explained as reduced forward stroke volume. Results of the current study were consistent with these previous investigations. Consequently, Tei index before surgery was significantly increased. After surgery, a nonsignificant increase in ET was observed without change in ICT and IRT. As a result, Tei index decreased, but without significance, after surgery. Clinical Implication It has been shown that Tei index expresses global LV function and is closely related to patients prognosis. Increased Tei index generally expresses poor prognosis. 3,6-8 The current study has demonstrated significant effects of valve dysfunction on Tei index. Tei index can be underestimated in the presence of AS, AR, or MS. Tei index can be overestimated in the presence of MR. Therefore, the results indicate the importance of careful estimation on valve dysfunction to evaluate ventricular function using Tei index. Evaluation of valve function is important especially

6 882 Haque et al September 2002 Figure 6 Changes in cardiac time intervals by valve surgery in mitral regurgitation. ICT, Isovolumic contraction time; IRT, isovolumic relaxation time; ET, ejection time; *P.05; **P.01; ***P.001. in patients with AS, because its influence on Tei index was maximal and approximate prediction of change in Tei index can also be performed by peak aortic flow velocity before the surgery. Limitations We demonstrated significant changes in cardiac time intervals and Tei index after valve surgery. These changes express effects of improved valve function and also effects of changes in LV function by the surgery. These effects were not separated, therefore, pure effects of valve dysfunction on Tei index may not be clearly shown in this study. For instance, increased Tei index after surgery in patients with AS may indicate effects from functional improvement of AV or deteriorated LV function after surgery. However, other echocardiographic findings, including smaller LV systolic dimensions and maintained fractional shortening after surgery, suggest no deterioration in LV function. Therefore, changes in cardiac time intervals and Tei index after valve surgery mainly suggest effects of functional improvement of diseased valve rather than effects of functional changes in the LV. In patients with AR and MR, there is no clear ICT and IRT. Therefore, clinical significance of ICT or MV closure to AV opening time and IRT or AV closure to MV opening time in these patients has not been established. However, previous reports suggested a relationship between these time intervals and cardiac function or severity of congestive heart failure in patients with AR and MR. 22,34 Therefore, estimation of cardiac time intervals or Tei index in patients with valvular diseases has potential clinical use. However, evaluation of ventricular function or long-term patients prognosis, which is expected to express true ventricular function, were not established from this study because the follow-up interval of the patients was only 1 month and the number of patients with clear LV dysfunction was limited. Further investigations in a large number of patients to follow-up clinical outcome are necessary to establish use. CONCLUSION Tei index significantly changes after valve surgery, especially in patients with AS. Therefore, considerations for the effects of valve dysfunction on Tei index are required for its application to evaluate ventricular function in patients with valve disease. REFERENCES 1. Tei C. New non-invasive index for combined systolic and diastolic ventricular function. J Cardiol 1995;26: Tei C, Ling LH, Hodge DO, Bailey KR, Oh JK, Rodeheffer RJ, et al. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function a study in normals and dilated cardiomyopathy. J Cardiol 1995;26: Tei C, Dujardin KS, Hodge DO, Baily KR, McGoon MD, Tajik AJ, et al. Doppler echocardiographic index for assess-

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