INTRODUCTION
In clinical practice, we use many indices of cardiac function, such as left ventricular ejection fraction (LVEF), maximal positive or negative pressure/time change (dP/dt), Tau (τ), stiffness, maximum elastance, and others. The number of indices of cardiac function indicates that the left ventricle performs multiple roles during a single cardiac cycle, and each index of cardiac function expresses only a partial aspect of a heterogeneous process. This can explain frequent discrepancies between patients’ status and the value of functional indices. One such example is relatively preserved LVEF in patients with end-stage chronic heart failure due to cardiac amyloidosis ( Fig. 16-1 ). Why is LVEF often discrepant with patient status in cardiac amyloidosis? There can be two reasons: (1) LVEF does not express left ventricular (LV) diastolic function, which is severely impaired in this pathology, and (2) LVEF does not express true ventricular systolic function, especially in the presence of increased LV wall thickness.
Increased LV wall thickness, typically seen in patients with cardiac amyloidosis, hypertrophic cardiomyopathy, or hypertensive heart disease, decreases wall tension, which allows for good wall motion and ejection even in the presence of significant myocardial systolic dysfunction. Therefore, relatively preserved LVEF or wall motion in patients with cardiac amyloidosis does not mean that their systolic function is only mildly impaired. Severely prolonged isovolumic contraction time (ICT) (see Fig. 16-1 ), despite normal LVEF in patients with cardiac amyloidosis, highly suggests that systolic function is severely impaired. Further, normal LVEF in the presence of LV hypertrophy (LVH), typically seen in patients with “diastolic heart failure,” may not mean normal systolic function. Figure 16-2 shows a patient with typical diastolic heart failure, with heart failure symptoms, a normal EF, and LVH. Cardiac time interval analysis demonstrates abnormally prolonged ICT and isovolumic relaxation time (IRT), indicating significant impairment of both systolic and diastolic functions. Therefore, normal LVEF does not mean normal systolic function in patients with so-called diastolic heart failure, which is one of the most common causes of chronic heart failure (HF). The 2005 guidelines of the American Heart Association/American College of Cardiology prefers “HF and Normal LVEF” for this entity and does not use the phrase “diastolic heart failure.” Even in patients with dilated cardiomyopathy, frequently considered as pure systolic dysfunction, it is known that LVEF only fairly correlates with exercise capacity, which is closely related to patient status and prognosis. Being the most representative index of cardiac function, LVEF expresses only systolic ejection among multiple aspects of systolic and diastolic functions.
Therefore, we often encounter discrepancies between values of cardiac functional indices and patient status. Physicians need to evaluate patient status subjectively by combining multiple sources of information, including various indices of cardiac function. In this context, it is reasonable to create an index of cardiac function, which can be a global expression combining systole and diastole or multiple aspects of heterogeneous LV function.
Concept of the Tei Index
Due to the big clinical need for an index expressing global cardiac function, the concept of the Tei index has been postulated. ICT is inversely proportional to LV peak positive dP/dt and expresses systolic contraction ( Fig. 16-3 ). LV ejection time (ET) is proportional to stroke volume, which can be reduced either by systolic or diastolic dysfunction. IRT is inversely proportional to LV peak negative dP/dt and expresses diastolic relaxation. However, these cardiac time intervals are heart rate dependent. Systolic dysfunction can result in prolonged ICT and shortened ET. Therefore, ICT/ET (which is ICT corrected by ET) can be a sensitive index to express systolic dysfunction. ICT/ET is also expected to be heart rate independent, due to the cancellation of heart rate dependencies of ICT and ET. For the same reason, IRT/ET (which is IVT corrected by ET) can be a sensitive and heart-rate-independent index to express diastolic function. The sum of ICT/ET and IRT/ET is the Tei index. Therefore, the Tei index has the potential to express combined systolic and diastolic or global cardiac function.
PATHOPHYSIOLOGY
Measurement of the Tei Index
The Tei index can be measured practically with conventional Doppler echocardiography. Interval a between cessation and re-onset of mitral filling flow includes ICT, ET, and IRT ( Fig. 16-4 ). Interval b between onset and cessation of aortic ejection flow equals ET. Therefore, the Tei index can be obtained by the following formula:
Tei index = ( a – b ) / b = ( ICT + IRT ) / ET .
This measurement is simple, practical, and reproducible. Multiple investigators in multiple institutions have measured the Tei index with almost identical normal values with a narrow range both for the LV and the right ventricular (RV) Tei index. The normal LV and RV Tei indices in our institution are 0.38 ± 0.04 and 0.28 ± 0.04, respectively.
Although standard pulsed Doppler echocardiographic measurement of the Tei index is practical and reproducible, multiple investigators have applied alternative approaches. One such approach is to utilize pulsed tissue Doppler annular velocity to measure the Tei index. This method has the merit of measuring intervals a and b simultaneously in a single cardiac cycle, while standard pulsed flow Doppler echocardiography requires measurement of intervals a and b in different cardiac cycles. Multiple investigators have reported that the Tei index by pulsed tissue Doppler echocardiography correlates well with that by pulsed flow Doppler echocardiography. However, discrepancy between the tissue Doppler Tei index and the flow Doppler Tei index has also been reported. It may be questionable whether the Tei index from tissue Doppler annular velocity expresses global cardiac function. Other approaches, including M-mode color tissue Doppler echocardiogram of mitral leaflets and conventional M-mode echocardiogram of mitral and aortic leaflets, have been utilized to measure the Tei index, with good agreement with the standard pulsed Doppler flow method. The LV area/time curve by automated border detection was also utilized to measure the Tei index, with good agreement with the standard pulsed flow Doppler method.
CLINICAL RELEVANCE
The Tei index was initially measured in normal subjects as well as in patients with clear RV or LV dysfunction. The value of the Tei index has a narrow range in normal subjects. The RV Tei index is clearly increased (0.67 ± 0.20) in patients with RV dysfunction, such as those with RV infarction, dysplasia, or cor pulmonale. The LV Tei index is also clearly increased (0.92 ± 0.22) in patients with idiopathic or ischemic cardiomyopathies ( Fig. 16-5 ). There is no overlap of values between normal subjects and patients with clear RV or LV dysfunction. Therefore, the Tei index is clearly abnormal in patients with a significant level of such dysfunction.
Load Dependency of the Tei Index
Because load dependency needs to be evaluated for all indices of cardiac function, the Tei index has also been evaluated regarding its load dependency. Studies have shown no significant correlation between heart rate and the Tei index in normal subjects. Dependency for heart rate has further been investigated by changing heart rate in patients with a pacemaker implantation. The Tei index significantly increased with elevation of heart rate in this study. However, the increase was subtle, from a mean value of 0.40 at 50 bpm to 0.51 at 100 bpm. Therefore, the Tei index is generally heart rate independent in clinical practice. The Tei index has also been evaluated during preload modifications such as the Valsalva maneuver, leg lifting, or sublingual nitroglycerin administration in normal subjects as well as in patients with prior myocardial infarction. These preload alterations caused an increase in the Tei index, but only to a small degree (0.034 ± 0.05) in normal subjects, and did not cause significant changes in the Tei index in patients with prior myocardial infarction. Therefore, the Tei index is relatively preload independent in patients with cardiac disease. In addition, the Tei index has no significant correlation with blood pressure in patients with LV dysfunction.
Although these investigations indicate that the Tei index is generally load independent, aortic stenosis causes it to significantly reduce. After surgery for valvular heart disease, patients with aortic stenosis showed a significant 29% increase in the Tei index, while those with aortic regurgitation, mitral stenosis, or regurgitation showed only minor changes. Correction of the prolongation of ET by aortic stenosis was the main cause of increase in the Tei index after surgical valve replacement.
The Tei Index and Prognosis
Because the Tei index is a global expression, it is related to multiple pathophysiologic parameters of cardiac function. The prognostic utility of the Tei index was initially evaluated in patients with cardiac amyloidosis. In this study, patients with a greater Tei index had significantly worse survival ( Fig. 16-6 ). Of note is that the Tei index enabled better separation of patients with poorer and better survival compared with LVEF. After this initial study, many studies have demonstrated the utility of the Tei index to evaluate prognosis in dilated cardiomyopathy, prior or acute myocardial infarction, chronic HF, and others. A strong relation between the Tei index and prognosis in patients with coronary artery disease suggests that the index may enable prediction of complications after acute myocardial infarction. An increased Tei index at admission to a coronary care unit predicted subsequent development of complications ( Fig. 16-7 ). An increased Tei index greater than 0.70 before mitral valvuloplasty is also a risk factor, doubling postoperative mortality. Recently, the utility of the Tei index to predict development of chronic HF or cardiac death has been demonstrated in a population-based cohort of elderly men. Therefore, an increased Tei index is a risk factor for the development of chronic HF as well as cardiac death.
Detection of Cardiac Dysfunction in Various Diseases
Multiple studies have reported that rejection after cardiac transplantation can cause myocardial damage and result in an increase in the Tei index. The Tei index is also significantly correlated with exercise capacity in several studies. Dobutamine stress echocardiography often requires subjective evaluation in patients with unclear response of LV wall motion. The Tei index showed significant increase at peak stress only in patients with positive response for ischemia, suggesting an incremental role of the Tei index in evaluation by dobutamine stress echocardiography. Reperfusion in patients with acute myocardial infarction results in an improvement in cardiac function. An increased Tei index of greater than 0.50 suggests absence of adequate reperfusion with thrombolysis in myocardial infarction (TIMI) grade 3 in patients with acute anteroseptal myocardial infarction ( Fig. 16-8 ).
Because abnormalities in ICT, ET, and IRT by cardiac dysfunction can be augmented in ICT/ET and IRT/ET, the Tei index has the potential to express subtle changes in cardiac function. Many investigators have applied the Tei index to detect small changes in cardiac function by various conditions, including hypothyroidism, diabetes mellitus, acromegaly, preconditioning with preceding angina, sleep apnea syndrome, and others.
Hemodynamic Assessment
As expected from its definition, the Tei index has close correlation with both systolic and diastolic functions, such as maximal + and − LV dP/dt, maximum mitral E-wave velocity, and τ. Although the Tei index does not include mid- to late-diastolic components, it has fair but significant correlation with LV stiffness. The Tei index is also significantly correlated with LV diastolic filling pressure. However, the correlation with pressure is modest, potentially due to the fact that LV filling pressure is determined by both ventricular function and loading. Nevertheless, the Tei index enables practical evaluation of impaired hemodynamics in patients with acute myocardial infarction with potentially minimal modification of loading in the acute phase before aggressive interventions to alter loading.
A Tei index greater than 0.6 suggests impaired hemodynamics with Forrester classifications II–IV in patients with acute anteroseptal myocardial infarction ( Fig. 16-9 ). Further, the Tei index enables practical differentiation of normal from pseudonormal mitral flow, defined by mitral E/A greater than 1.0 with elevated LV filling pressure. It may seem strange that the Tei index practically separates patients with mitral E/A greater than 1.0 with or without elevated LV filling pressure, while the index is only fairly correlated with filling pressure. The Tei index shows significant and better correlation with LV filling pressure in patients with mitral E/A greater than 1.0 compared with those with mitral E/A no greater than 1.0 because LV function and its filling pressure can be placed into four categories ( Fig. 16-10 ) :
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Category I: normal LV function and normal filling pressure
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Category II: poor LV function and normal filling pressure
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Category III: normal LV function and high filling pressure
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Category IV: poor LV function and high filling pressure
