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Differentiation of Left Ventricular Diastolic Function by Mid-Diastolic Mitral Annular Motion Patterns
Ultrasound in Med. & Biol., Vol. 34, No. 5, pp. 753–759, 2008 Copyright © 2008 World Federation for Ultrasound in Medicine & Biology Printed in the USA. All rights reserved 0301-5629/08/$–see front matter
doi:10.1016/j.ultrasmedbio.2007.11.008
● Original Contribution DIFFERENTIATION OF LEFT VENTRICULAR DIASTOLIC FUNCTION BY MID-DIASTOLIC MITRAL ANNULAR MOTION PATTERNS HO-MING SU,*† TSUNG-HSIEN LIN,* CHEE-SIONG LEE,* HSUEH-WEI YEN,* CHIH-HSIN HUANG,* KAI-HUNG CHENG,*† HSIANG-CHUN LEE,* WEN-TER LAI,* SHENG-HSIUNG SHEU,* and WEN-CHOL VOON* *Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University and †Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan (Received 5 June 2007, revised 14 October 2007, in final form 12 November 2007)
Abstract—Mid-diastolic mitral annular motion may be driven by strain energy, an energy for myocardial recoil, stored during the previous systole. Hence, various patterns of mid-diastolic mitral annular motion may imply different left ventricular (LV) diastolic function. The purpose of this study is to compare LV diastolic properties among different types of mid-diastolic mitral annular motion. Two-hundred and three consecutive subjects underwent an echocardiographic examination at our outpatient clinic. Study subjects were classified into three groups according to mid-diastolic mitral annular motion patterns. Upward and downward La waves were defined, respectively, as a clear apically and atrially directed mid-diastolic annular motion on at least three consecutive beats with the average peak velocity >2 cm/s. Subjects with upward La wave, with downward but without upward La wave and without La wave were categorized as groups 1, 2 and 3, respectively. Early diastolic mitral annular velocity (Ea) was higher and the ratio of transmitral E wave velocity to Ea was lower in group 1 than in groups 2 and 3 (all p < 0.001). The diagnostic accuracy of upward La wave in prediction of normal diastolic function fell between 75% and 88%. In conclusion, patients with upward La wave had better LV diastolic function and lower LV filling pressure than patients without it. Upward La wave is useful in prediction of normal diastolic function. Therefore, analysis of mid-diastolic mitral annular motion may be complementary to other measures of LV diastolic function. (E-mail: [email protected]) © 2008 World Federation for Ultrasound in Medicine & Biology. Key Words: Mid-diastolic mitral annular motion, Tissue Doppler echocardiography, Diastolic function, Filling pressure.
assessment of diastolic dysfunction. Pulsed wave Doppler transmitral inflow variables remain the cornerstone of the evaluation of diastolic function (Nishimura et al. 1997). Although mitral inflow usually consists of two forward flows, i.e., mitral E and A waves, it may occasionally have additional forward flow during mid-diastole. (Hatle et al. 1993; Keren et al. 1986). The mitral L wave, defined as a forward mitral inflow during middiastole, with a peak velocity ⱖ20 cm/s, was reported to be a marker of advanced diastolic dysfunction and predictor of future heart failure events (Ha et al. 2004; Lam et al. 2005). Tissue Doppler echocardiography provides a regional approach to cardiac wall kinetics through myocardial velocity measurements. The early diastolic mitral annular velocity (Ea) has been shown to be a useful parameter of myocardial relaxation (Nagueh et al. 1997).
INTRODUCTION Heart failure is a common cause of cardiovascular death and may occur in the presence of either a normal or abnormal left ventricular ejection fraction (EF) (Levy et al. 2002; Lloyd-Jones et al. 2002; Jessup et al. 2003). Diastolic heart failure, or heart failure with a preserved left ventricular systolic function, is a growing epidemic (Cowie et al. 1999; Senni et al. 1998; Vasan et al. 1999). Diastolic dysfunction itself has substantial adverse prognostic significance, demonstrating the importance of proper diagnosis of diastolic dysfunction. Doppler echocardiography is the noninvasive method of choice for the Address correspondence to: Wen-Chol Voon, MD, Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University, 100 Tz-You 1st Road, Kaohsiung City 807, Taiwan. E-mail: [email protected] 753
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The E/Ea has also been correlated with left ventricular filling pressure (Nagueh et al. 1997; Ommen et al. 2000). In contrast with the numerous studies regarding Ea (Nagueh et al. 1997; Ommen et al. 2000), the studies about mid-diastolic mitral annular motion are fewer. Ha et al. (2006) have even shown that the presence of a mid-diastolic mitral annular motion in patients with triphasic mitral inflow velocity pattern indicates advanced diastolic dysfunction and elevated left ventricular filling pressure. In addition, Riordan and Kovács (2007) demonstrated that patients without diastolic mitral annular oscillations after the Ea wave had relaxation-related diastolic dysfunction. Mid-diastolic mitral annular motion may be driven by strain energy, an energy for myocardial recoil, stored during the previous systole. Hence, various types of mid-diastolic mitral annular motion may imply different diastolic function. However, to date, few data are available regarding the relationship between mid-diastolic mitral annular motion patterns and left ventricular diastolic function. Hence, the purpose of this study is to compare the left ventricular diastolic properties and filling pressures among different types of mid-diastolic mitral annular motion. METHODS Study patients Two-hundred and twenty-one consecutive subjects under an echocardiographic examination recruited from our cardiologic outpatient clinic were screened for this study. Ten patients with significant mitral valve disease and eight patients with inadequate echocardiographic visualization were excluded. The remaining 203 patients formed our study group. All patients were in sinus rhythm. The protocol was approved by our Institutional Review Board and all enrolled patients gave written, informed consent. The study subjects were classified into three groups on the basis of the mid-diastolic mitral annular motion patterns (Fig 1). If a subject had upward La wave, defined as a clear apically-directed mid-diastolic annular motion on at least three consecutive beats with its average peak velocity ⱖ2 cm/s, he was entered into group 1 (Fig. 1a and b). If a subject had downward La wave, defined as a clear atrially-directed mid-diastolic annular motion on at least three consecutive beats, with its average peak velocity ⱖ2 cm/s, but had no upward La wave, he was entered into group 2 (Fig. 1c). The other study subjects without upward or downward La wave were classified into group 3 (Fig. 1d). The setting of lowest velocity limit of La wave (2 cm/s) was mainly to avoid the interference of background noise with the verification of the presence or absence of La wave.
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Doppler echocardiographic evaluation The echocardiographic examination was performed with a Vivid 7 (General Electric Medical Systems, Horten, Norway), with the participant respiring quietly in the left decubitus position. Two-dimensional and twodimensionally guided M-mode images were recorded from the standardized views. The Doppler sample volume was placed at the tips of the mitral leaflets to get the left ventricular inflow waveforms from the apical fourchamber view. All sample volumes were positioned with ultrasonic beam alignment to flow. Tissue Doppler imaging was obtained, with the sample volume placed at the lateral corner of the mitral annulus from the apical four-chamber view. The wall filter settings were adjusted to exclude high-frequency signals and the gain was minimized. The Doppler waveforms were recorded on a magneto-optical disc for later analysis. In addition, to evaluate the relationship between mid-diastolic mitral annular motion patterns and stages of left ventricular diastolic dysfunction, we also categorized our study subjects according to mitral inflow filling patterns. The mitral inflow filling patterns were classified into three types as normal, abnormal relaxation and pseudo-normal/restrictive types on the basis of E/A, Ea and E/Ea. The normal filling pattern was recognized if E/A ratio was ⬎0.9, Ea ⬎8 cm/s and E/Ea ⬍10; abnormal relaxation filling pattern if E/A ratio was ⱕ0.9; and pseudo-normal/restrictive filling pattern if E/A ratio was ⬎0.9 and Ea ⱕ8 cm/s or E/Ea ⱖ10 (Bruch et al. 2000; Farias et al. 1999; Firstenberg et al. 2000; Garica et al. 1998; Khouri et al. 2004; Nagueh et al. 1997). Statistical analysis All data were expressed as mean (⫾ standard deviation). SPSS 11.0 (SPSS, Inc., Chicago, IL, USA) was used for statistical analysis. Multiple comparisons between the study groups were performed by one-way analysis of variance (ANOVA) followed by post hoc test adjusted with a Bonferroni correction. Categorical variables were compared by chi-square analyses. All tests were two-sided, and the level of significance was established as p ⬍ 0.05. RESULTS The clinical and echocardiographic characteristics among the study groups are shown in Table 1. The patients in group 1 were younger than those in groups 2 and 3 (both p ⬍ 0.001). The prevalence rate of diabetes mellitus and hypertension was lower in group 1 than in groups 2 and 3 (p ⱕ 0.026). The study was done with the patients taking their usual medications. Heart rate was not different among groups. Left atrial dimension (LA) and left ventricular end-diastolic
Mitral La wave and LV diastolic function ● H.-M. SU et al.
Fig 1. Doppler tissue images of the lateral mitral annulus from representative patients. Case A is a patient with apically-directed mid-diastolic annular motion (upward La wave) but without atrially-directed mid-diastolic annular motion (downward La wave) on each beat. Case B is a patient with alternating upward and downward La waves on each beat. Case C is a patient with downward, but not upward, La wave on each beat. Case D is a patient without La wave. Aa ⫽ late diastolic mitral annular velocity; Ea ⫽ early diastolic mitral annular velocity.
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Table 1. Distribution of various mitral inflow filling patterns in each group
Number (%) Age (y) Sex (M/F) Diabetes mellitus (%) Hypertension (%) Medications -blockers (%) CCBs (%) ACEIs (%) ARBs (%) Heart rate (beats/min) LA (mm) LVEDD (mm) LVESD (mm) E (cm/s) A (cm/s) E/A EDT (ms) Ea (cm/s) E/Ea Aa (cm/s) S (cm/s) IVRT (ms) EF (%)
Group 1
Group 2
Group 3
p
95 (47%) 50 ⫾ 16 44/51 10 34
37 (18%) 63 ⫾ 12* 19/18 24* 65*
71 (35%) 63 ⫾ 12* 41/30 34* 52*
⬍ 0.001 0.346 0.001 0.002
32 11 13 14 68 ⫾ 9 34 ⫾ 6 49 ⫾ 5 29 ⫾ 5 81 ⫾ 16 70 ⫾ 17 1.23 ⫾ 0.39 194 ⫾ 45 11.7 ⫾ 3.4 7.4 ⫾ 2.3 9.0 ⫾ 2.0 10.0 ⫾ 2.5 74 ⫾ 17 71 ⫾ 9
54 32 32 27 69 ⫾ 14 39 ⫾ 6* 54 ⫾ 8* 36 ⫾ 11* 82 ⫾ 24 83 ⫾ 24* 1.11 ⫾ 0.57 214 ⫾ 84 7.4 ⫾ 2.1* 11.6 ⫾ 4.2* 8.1 ⫾ 2.4 7.5 ⫾ 1.9* 86 ⫾ 19* 62 ⫾ 17*
32 28 20 28 72 ⫾ 11 36 ⫾ 6† 50 ⫾ 7† 31 ⫾ 8† 72 ⫾ 17*† 91 ⫾ 25* 0.83 ⫾ 0.28*† 229 ⫾ 70* 7.5 ⫾ 2.5* 10.6 ⫾ 4.4* 9.4 ⫾ 2.4† 7.9 ⫾ 2.2* 94 ⫾ 29* 67 ⫾ 12
0.059 ⬍ 0.001 ⬍ 0.001 ⬍ 0.001 0.002 ⬍ 0.001 ⬍ 0.001 0.002 ⬍ 0.001 ⬍ 0.001 0.019 ⬍ 0.001 ⬍ 0.001 ⬍ 0.001
A ⫽ peak late transmitral filling wave velocity; Aa ⫽ late diastolic velocity of lateral mitral annulus; ACEIs ⫽ angiotensin-converting enzyme inhibitors; ARBs ⫽ angiotensin II receptor antagonists; CCBs ⫽ calcium channel blockers; E ⫽ peak early transmitral filling wave velocity; Ea ⫽ early diastolic velocity of lateral mitral annulus; EDT ⫽ E-wave deceleration time; EF ⫽ ejection fraction; IVRT ⫽ isovolumic relaxation time; LA ⫽ left atrial dimension; LVEDD ⫽ left ventricular end-diastolic dimension; LVESD ⫽ left ventricular end-systolic dimension; S ⫽ systolic velocity of lateral mitral annulus. * 0.05 compared with group 1; † p ⬍ 0.05 compared with group 2.
and end-systolic dimensions (LVEDD and LVESD) were larger in group 2 than in groups 1 and 3 (p ⱕ 0.031). E and E/A were lower in group 3 than in groups 1 and 2 (p ⱕ 0.020). A was lower in group 1 than in groups 2 and 3 (p ⱕ 0.007). E-wave deceleration time (EDT) was longer in group 3 than in group 1 (p ⫽ 0.001). Ea and peak systolic mitral annular velocity (S) were higher, E/Ea was lower and isovolumic relaxation time (IVRT) was shorter in group 1 than in groups 2 and 3 (p ⱕ 0.014). Late diastolic mitral annular velocity (Aa) was lower in group 2 than in group 3 (p ⫽ 0.015). Left ventricular EF was lower in group 2 than in group 1 (p ⬍ 0.001). To exclude the influence of age on left ventricular diastolic function and filling pressure, we performed a subgroup analysis in 50 ⬍ patients ⱕ70 years old. In this subgroup analysis, age was not different among groups (p ⫽ 0.133). However, Ea was higher and E/Ea was lower in group 1 than in groups 2 and 3 (p ⱕ 0.044). To eliminate the influence of hypertension and diabetes mellitus on left ventricular diastolic function and filling pressure, we performed another subgroup analysis in the patients without these two diseases. Similarly, Ea was higher and E/Ea was lower in group 1 than in groups 2 and 3 (all p ⬍ 0.001). In addition, the third subgroup
analysis was performed in patients with left ventricular EF ⬎50% and, likewise, Ea was higher and E/Ea was lower in group 1 than in groups 2 and 3 (all p ⬍ 0.001), whereas left ventricular EF was not different among groups (p ⫽ 0.734). In our study, there were 14 patients (7%) with mitral L wave. Among them, there were nine patients (64%) with only downward La wave. In other words, in group 2 (n ⫽ 37), there were nine patients with mitral L wave but 28 patients without it. Besides, in group 2, the heart rate in nine patients with mitral L wave was slower than that in 28 patients without mitral L wave (59 ⫾ 9 vs. 72 ⫾ 13 beats/min, p ⫽ 0.013). Table 2 shows the distribution of various mitral inflow filling patterns in each group. In group 1, there were 71 (75%), 21 (22%) and 3 (3%) patients with
Table 2. Comparison of clinical and echocardiographic characteristics in study subjects Group 1 Group 2 Group 3 Normal filling pattern Abnormal relaxation filling pattern Pseudo-normal/restrictive filling pattern
71 21 3
5 15 17
8 47 16
Mitral La wave and LV diastolic function ● H.-M. SU et al.
normal, abnormal relaxation and pseudo-normal/restrictive filling patterns, respectively. The most common mitral inflow filling pattern in group 1 was normal filling pattern. In group 2, there were 5 (14%), 15 (41%) and 17 (46%) patients with normal, abnormal relaxation and pseudo-normal/restrictive filling patterns, respectively. Patients with abnormal mitral inflow filling patterns were more common than those with normal filling patterns in group 2 (p ⬍ 0.001). In group 3, there were 8 (11%), 47 (66%) and 16 (23%) patients with normal, abnormal relaxation and pseudo-normal/restrictive filling patterns, respectively. The most common mitral inflow filling pattern in group 3 was abnormal relaxation filling pattern (p ⬍ 0.001). The prevalence of upward La wave was 71 among the 84 patients with normal diastolic function (patients with normal filling pattern) and 24 among the 119 patients with abnormal diastolic function (patients with abnormal relaxation or pseudo-normal/restrictive filling pattern). Therefore, the sensitivity, specificity, positive and negative predictive values and accuracy of upward La wave in prediction of normal diastolic function were 85%, 80%, 75%, 88% and 82%, respectively. DISCUSSION Ea has been correlated with the time constant of left ventricular isovolumic pressure decrease (tau) and reported to be a noninvasive surrogate of myocardial relaxation (Sohn et al. 1997). E/Ea has been shown to be a good predictor of left ventricular filling pressure (Ommen et al. 2000). In this study, we found that Ea was higher and E/Ea was lower in group 1 than in groups 2 and 3. This finding suggested that patients with upward La wave may have better left ventricular relaxation function and lower left ventricular filling pressure than patients with only downward La wave and patients without La wave. Zaky et al. (1967) first noted that annular motion sometimes reverses direction after the initial Ea wave and may have clinical importance. Much later, Isaaz et al. (1993) described the continuous, alternating atrially and apically directed motion of the mitral annulus during the cardiac cycle and assumed that the balance between stored elastic potential energy and kinetic energy plays a role. Recently, Riordan and Kovács (2007) demonstrated that longitudinal annular motion during early and middiastolic filling as driven by strain energy stored during the previous systole and overshoots its equilibrium position and reverses direction (toward the apex) in certain subjects. They further found that patients with diastolic mitral annular oscillation had a shorter tau and IVRT, greater E/A and Ea and lower E/Ea than patients without diastolic mitral annular oscillation. Mitral annular mo-
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tion always overshoots its equilibrium position and reverses direction (toward apex) in the patients of group 1. Hence, the mitral annular motion in the patients of group 1 obeyed the mitral annular oscillation and, in compatibility with previous finding (Riordan and Kovács 2007), the patients in group 1 had shorter IVRT, greater Ea and lower E/Ea than the patients in the other groups. The patients in group 2 had only downward La wave. Mitral annular motion did not overshoot its equilibrium position but maintained in the downward direction (toward the left atrium). Hence, the mitral annular motion did not obey the diastolic mitral annular oscillation in the patients of group 2, so their left ventricular diastolic function was not as good as that in the patients of group 1. Ha et al. (2006) found that the presence of downward La wave in subjects with triphasic mitral inflow velocity pattern with mid-diastolic flow indicated advanced diastolic dysfunction and elevated left ventricular filling pressure. Although our study patients did not restrict to subjects with triphasic mitral inflow velocity pattern, the patients in group 2 similarly had more advanced diastolic dysfunction and higher left ventricular filling pressure than the patients in group 1. Riordan and Kovács (2007) found that the elastic strain energy was reduced and the resistance to left ventricular filling was increased in patients without diastolic mitral annular oscillation and showed that the absence of diastolic mitral annular oscillation was a marker for relation-related diastolic dysfunction. In our study, the patients in group 3 had neither upward nor downward La wave. Hence, there was no clear middiastolic mitral oscillation on three consecutive beats in the patients of group 3. In concordance with the finding of Riordan and Kovács (2007), the left ventricular diastolic function was worse and left ventricular filling pressure was higher in group 3 than in group 1. In addition, although the LA, LVEDD and LVESD were larger in the patients of group 2 than group 3, the Ea and E/Ea were similar between them. Hence, the diastolic function and left ventricular filling pressure were comparable in these two groups. Left ventricular diastolic function is known to depend on age (Nikitin et al. 2005). Because the patients in group 1 were younger than those in groups 2 and 3, the age difference may partially explain the better diastolic function and lower filling pressure in group 1. However, in the subgroup analysis involving the 50 ⬍ patients ⱕ70 years old, Ea was higher and E/Ea was lower in group 1 than in groups 2 and 3, whereas age was not different among groups. Therefore, age was not the major reason for better diastolic function and lower filling pressure in group 1. Hypertension and diabetes mellitus are reported to be detrimental to left ventricular diastolic function. In our study, these two diseases are less prevalent in group
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1 than in groups 2 and 3, so this difference in prevalence rate may cause the better diastolic function in group 1. However, after exclusion of subjects with these two diseases, Ea was also higher and E/Ea was also lower in group 1 than in groups 2 and 3. Hence, hypertension and diabetes mellitus were not the main cause of different diastolic function and filling pressure among groups. In addition, pathologic processes with cardiac involvement generally have an impact on the diastolic followed by systolic function of the ventricles. Thus, the patients with systolic function impairment are usually combined with advanced diastolic dysfunction. In our study, left ventricular systolic function was worse in group 2 than in groups 1 and 3; the difference in systolic function may confound our results. However, the subgroup analysis in patients with normal left ventricular systolic function showed that Ea was still higher and E/Ea was still lower in group 1 than in groups 2 and 3, whereas left ventricular EF was not different among groups. Consequently, left ventricular systolic function was also not the major reason of our findings. In a previous study by Lam et al. (2005), the mitral L wave was present in 20% of the patients. However, in another study by Ha et al. (2006), the mitral L wave was only present in 0.9% of the patients. In our study, the mitral L wave was present in 7% of the patients. In the study by Ha et al. (2004), Valsalva maneuver could abolish the mitral L wave in 59% of patients and leg elevation of the patient could produce the mitral L wave. Hence, preload has a pronounced effect on the development of mitral L wave. Slow heart rate was reported to be a prerequisite for the genesis of mitral L wave (Ha et al. 2004). Hence, the various heart rate and preload status may explain the diverse prevalence rates of mitral L wave among the different studies. In addition, in group 2, the heart rate in nine patients with mitral L wave was slower than that in 28 patients without mitral L wave. Therefore, the difference in heart rate may partially explain the presence or absence of mitral L wave in group 2. In patients with upward La wave, their longitudinal stored elastic strain, force and strain-energy were increased, suggesting the availability of more energy for myocardial recoil (Riordan and Kovács 2007). Hence, the relaxation function in patients with upward La wave should be good. This may explain that 75% of patients had normal mitral inflow filling pattern in group 1. However, there were still 25% of patients in group 1 showing abnormal physiology by mitral inflow filling pattern. Riordan and Kovács (2006) applied and validated damped simple harmonic oscillatory motion as the kinematic principle that governs mitral annular oscillations. These physics predict an oscillatory (stiffness ⬎ relaxation/viscoelasticity) regime for annular motion, as well as a nonoscillatory (stiffness ⬍ relaxation/viscoelastic-
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ity) regime. Hence, the presence of mitral annular oscillation is determined by multiple factors, not solely by relaxation function. This may explain why there were still 25% of patients in group 1 showing abnormal physiology by mitral inflow filling pattern. By contrast, in patients without upward La wave, their relaxation function may be impaired. This may explain that most of patients had abnormal mitral inflow filling patterns and only 14% and 11% of patients had normal filling pattern in groups 2 and 3. Therefore, upward La wave may be useful in predicting normal diastolic function. Increased heart rate can cause a decrease in the duration of diastasis (Chung and Kovács SJ 2006). Hence, higher heart rate may cause merging of Ea and Aa waves and preclude the identification of La wave. In our study, we did not exclude the subjects with higher heart rates. Therefore, patients in group 3 might shift to other groups if their heart rate decreased. However, in our study, heart rate was not different among groups and the highest heart rates in group 1, 2 and 3 were 109, 107 and 96 beats/min, respectively. Hence, La wave could be identified when heart rate was ⬎100 beats/min. Because the heart rates of patients in group 3 were all ⬍100 beats/min, the confounding effect of heart rate in identification of La wave in our study might be neglected. Study limitations In this study, we did not have invasive hemodynamic correlation of our findings. However, a study is underway to address this issue. In addition, we did not record mitral annular velocity pattern from various sites. Although the lateral annular velocity pattern is more reproducible than the septal one (Khoure et al. 2004) and it is echocardiographically easier to localize the sample volume at the lateral aspect and thereby minimize the likelihood of including myocardial tissue velocities, the analysis of annular velocity patterns from various sites may provide more information. In conclusion, patients with upward La wave had better left ventricular diastolic function and lower left ventricular filling pressure than patients without it. Upward La wave is useful in predicting normal diastolic function. Therefore, analysis of mid-diastolic mitral annular motion may be complementary to other measures of left ventricular diastolic function. REFERENCES Bruch C, Schmermund A, Bartel T, Schaar J, Erbel R. Tissue Doppler imaging: A new technique for assessment of pseudonormalization of the mitral inflow pattern. Echocardiography 2000;17:539 –546. Chung CS, Kovács SJ. Consequences of increasing heart rate on deceleration time, the velocity-time integral, and E/A. Am J Cardiol 2006;97:130 –136.
Mitral La wave and LV diastolic function ● H.-M. SU et al. Cowie MR, Wood DA, Coats AJ, Thompson SG, Poole-Wilson PA, Suresh V, Sutton GC. Incidence and aetiology of heart failure; a population-based study. Eur Heart J 1999;20:421– 428. Farias CA, Rodriguez L, Garcia MJ, Sun JP, Klein AL, Thomas JD. Assessment of diastolic function by tissue Doppler echocardiography: Comparison with standard transmitral and pulmonary venous flow. J Am Soc Echocardiogr 1999;12:609 – 617. Firstenberg MS, Levine BD, Garcia MJ, Greenberg NL, Cardon L, Morehead AJ, Zuckerman J, Thomas JD. Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers. J Am Coll Cardiol 2000;36:1664 –1669. Garcia MJ, Thomas JD, Klein AL. New Doppler echocardiographic applications for the study of diastolic function. J Am Coll Cardiol 1998;32:865– 875. Ha JW, Ahn JA, Moon JY, Suh HS, Kang SM, Rim SJ, Jang Y, Chung N, Shim WH, Cho SY. Triphasic mitral inflow velocity with mid-diastolic flow: The presence of mid-diastolic mitral annular velocity indicates advanced diastolic dysfunction. Eur J Echocardiogr 2006;7:16 –21. Ha JW, Oh JK, Redfield MM, Ujino K, Seward JB, Tajik AJ. Triphasic mitral inflow velocity with middiastolic filling: Clinical implications and associated echocardiographic findings. J Am Soc Echocardiogr 2004;17:428 – 431. Hatle L. Doppler echocardiographic evaluation of diastolic function in hypertensive cardiomyopathies. Eur Heart J 1993;14 Suppl J:88 –94. Isaaz K, Munoz del Romeral L, Lee E, Schiller NB. Quantitation of the motion of the cardiac base in normal subjects by Doppler echocardiography. J Am Soc Echocardiogr 1993;6:166 –176. Jessup M, Brozena S. Heart failure. N Engl J Med 2003;348:2007– 2018. Keren G, Meisner JS, Sherez J, Yellin EL, Laniado S. Interrelationship of mid-diastolic mitral valve motion, pulmonary venous flow, and transmitral flow. Circulation 1986;74:36 – 44. Khouri SJ, Maly GT, Suh DD, Walsh TE. A practical approach to the echocardiographic evaluation of diastolic function. J Am Soc Echocardiogr 2004;17:290 –297. Lam CS, Han L, Ha JW, Oh JK, Ling LH. The mitral L wave: A marker of pseudonormal filling and predictor of heart failure in patients with left ventricular hypertrophy. J Am Soc Echocardiogr 2005;18: 336 –341. Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ. Clinical utility of Doppler echocardiography and
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tissue Doppler imaging in the estimation of left ventricular filling pressures. Circulation 2000;102:1788 –1794. Levy D, Kenchaiah S, Larson MG, Benjamin EJ, Kupka MJ, Ho KK, Murabito JM, Vasan RS. Long-term trends in the incidence of and survival with heart failure. N Engl J Med 2002;347:1397–1402. Lloyd-Jones DM, Larson MG, Leip EP, Beiser A, D’Agostino RB, Kannel WB, Murabito JM, Vasan RS, Benjamin EJ, Levy D. Lifetime risk for developing congestive heart failure: The Framingham Heart Study. Circulation 2002;106:3068 –3072. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: A noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997;30:1527–1533. Nikitin NP, Witte KK, Ingle L, Clark AL, Farnsworth TA, Cleland JG. Longitudinal myocardial dysfunction in healthy older subjects as a manifestation of cardiac ageing. Age Ageing 2005;34:343–349. Nishimura RA, Tajik AJ. Evaluation of diastolic filling of left ventricle in health and disease: Doppler echocardiography is the clinician’s Rosetta Stone. J Am Coll Cardiol 1997;30:8 –18. Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures. Circulation 2000;102:1788 –1794. Riordan MM, Kovács SJ. Quantitation of mitral annular oscillations and longitudinal “ringing” of the left ventricle: A new window into longitudinal diastolic function. J Appl Physiol 2006;100:112–119. Riordan MM, Kovács SJ. Absence of diastolic mitral annular oscillations is a marker for relaxation-related diastolic dysfunction. Am J Physiol Heart Circ Physiol 2007;292:H2952–H2958. Senni M, Tribouilloy CM, Rodeheffer RJ, Jacobsen SJ, Evans JM, Bailey KR, Redfield MM. Congestive heart failure in the community: A study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation 1998;98:2282–2289. Sohn DW, Chai IH, Lee DJ, et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 1997;30:474 – 480. Vasan RS, Larson MG, Benjamin EJ, Evans JC, Reiss CK, Levy D. Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: Prevalence and mortality in a population-based cohort. J Am Coll Cardiol 1999;33:1948 –1955. Zaky A, Grabhorn L, Feigenbaum H. Movement of the mitral ring: A study in ultrasound cardiography. Cardiovasc Res 1967;1:121–131.
doi:10.1016/j.ultrasmedbio.2007.11.008
● Original Contribution DIFFERENTIATION OF LEFT VENTRICULAR DIASTOLIC FUNCTION BY MID-DIASTOLIC MITRAL ANNULAR MOTION PATTERNS HO-MING SU,*† TSUNG-HSIEN LIN,* CHEE-SIONG LEE,* HSUEH-WEI YEN,* CHIH-HSIN HUANG,* KAI-HUNG CHENG,*† HSIANG-CHUN LEE,* WEN-TER LAI,* SHENG-HSIUNG SHEU,* and WEN-CHOL VOON* *Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University and †Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan (Received 5 June 2007, revised 14 October 2007, in final form 12 November 2007)
Abstract—Mid-diastolic mitral annular motion may be driven by strain energy, an energy for myocardial recoil, stored during the previous systole. Hence, various patterns of mid-diastolic mitral annular motion may imply different left ventricular (LV) diastolic function. The purpose of this study is to compare LV diastolic properties among different types of mid-diastolic mitral annular motion. Two-hundred and three consecutive subjects underwent an echocardiographic examination at our outpatient clinic. Study subjects were classified into three groups according to mid-diastolic mitral annular motion patterns. Upward and downward La waves were defined, respectively, as a clear apically and atrially directed mid-diastolic annular motion on at least three consecutive beats with the average peak velocity >2 cm/s. Subjects with upward La wave, with downward but without upward La wave and without La wave were categorized as groups 1, 2 and 3, respectively. Early diastolic mitral annular velocity (Ea) was higher and the ratio of transmitral E wave velocity to Ea was lower in group 1 than in groups 2 and 3 (all p < 0.001). The diagnostic accuracy of upward La wave in prediction of normal diastolic function fell between 75% and 88%. In conclusion, patients with upward La wave had better LV diastolic function and lower LV filling pressure than patients without it. Upward La wave is useful in prediction of normal diastolic function. Therefore, analysis of mid-diastolic mitral annular motion may be complementary to other measures of LV diastolic function. (E-mail: [email protected]) © 2008 World Federation for Ultrasound in Medicine & Biology. Key Words: Mid-diastolic mitral annular motion, Tissue Doppler echocardiography, Diastolic function, Filling pressure.
assessment of diastolic dysfunction. Pulsed wave Doppler transmitral inflow variables remain the cornerstone of the evaluation of diastolic function (Nishimura et al. 1997). Although mitral inflow usually consists of two forward flows, i.e., mitral E and A waves, it may occasionally have additional forward flow during mid-diastole. (Hatle et al. 1993; Keren et al. 1986). The mitral L wave, defined as a forward mitral inflow during middiastole, with a peak velocity ⱖ20 cm/s, was reported to be a marker of advanced diastolic dysfunction and predictor of future heart failure events (Ha et al. 2004; Lam et al. 2005). Tissue Doppler echocardiography provides a regional approach to cardiac wall kinetics through myocardial velocity measurements. The early diastolic mitral annular velocity (Ea) has been shown to be a useful parameter of myocardial relaxation (Nagueh et al. 1997).
INTRODUCTION Heart failure is a common cause of cardiovascular death and may occur in the presence of either a normal or abnormal left ventricular ejection fraction (EF) (Levy et al. 2002; Lloyd-Jones et al. 2002; Jessup et al. 2003). Diastolic heart failure, or heart failure with a preserved left ventricular systolic function, is a growing epidemic (Cowie et al. 1999; Senni et al. 1998; Vasan et al. 1999). Diastolic dysfunction itself has substantial adverse prognostic significance, demonstrating the importance of proper diagnosis of diastolic dysfunction. Doppler echocardiography is the noninvasive method of choice for the Address correspondence to: Wen-Chol Voon, MD, Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University, 100 Tz-You 1st Road, Kaohsiung City 807, Taiwan. E-mail: [email protected] 753
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The E/Ea has also been correlated with left ventricular filling pressure (Nagueh et al. 1997; Ommen et al. 2000). In contrast with the numerous studies regarding Ea (Nagueh et al. 1997; Ommen et al. 2000), the studies about mid-diastolic mitral annular motion are fewer. Ha et al. (2006) have even shown that the presence of a mid-diastolic mitral annular motion in patients with triphasic mitral inflow velocity pattern indicates advanced diastolic dysfunction and elevated left ventricular filling pressure. In addition, Riordan and Kovács (2007) demonstrated that patients without diastolic mitral annular oscillations after the Ea wave had relaxation-related diastolic dysfunction. Mid-diastolic mitral annular motion may be driven by strain energy, an energy for myocardial recoil, stored during the previous systole. Hence, various types of mid-diastolic mitral annular motion may imply different diastolic function. However, to date, few data are available regarding the relationship between mid-diastolic mitral annular motion patterns and left ventricular diastolic function. Hence, the purpose of this study is to compare the left ventricular diastolic properties and filling pressures among different types of mid-diastolic mitral annular motion. METHODS Study patients Two-hundred and twenty-one consecutive subjects under an echocardiographic examination recruited from our cardiologic outpatient clinic were screened for this study. Ten patients with significant mitral valve disease and eight patients with inadequate echocardiographic visualization were excluded. The remaining 203 patients formed our study group. All patients were in sinus rhythm. The protocol was approved by our Institutional Review Board and all enrolled patients gave written, informed consent. The study subjects were classified into three groups on the basis of the mid-diastolic mitral annular motion patterns (Fig 1). If a subject had upward La wave, defined as a clear apically-directed mid-diastolic annular motion on at least three consecutive beats with its average peak velocity ⱖ2 cm/s, he was entered into group 1 (Fig. 1a and b). If a subject had downward La wave, defined as a clear atrially-directed mid-diastolic annular motion on at least three consecutive beats, with its average peak velocity ⱖ2 cm/s, but had no upward La wave, he was entered into group 2 (Fig. 1c). The other study subjects without upward or downward La wave were classified into group 3 (Fig. 1d). The setting of lowest velocity limit of La wave (2 cm/s) was mainly to avoid the interference of background noise with the verification of the presence or absence of La wave.
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Doppler echocardiographic evaluation The echocardiographic examination was performed with a Vivid 7 (General Electric Medical Systems, Horten, Norway), with the participant respiring quietly in the left decubitus position. Two-dimensional and twodimensionally guided M-mode images were recorded from the standardized views. The Doppler sample volume was placed at the tips of the mitral leaflets to get the left ventricular inflow waveforms from the apical fourchamber view. All sample volumes were positioned with ultrasonic beam alignment to flow. Tissue Doppler imaging was obtained, with the sample volume placed at the lateral corner of the mitral annulus from the apical four-chamber view. The wall filter settings were adjusted to exclude high-frequency signals and the gain was minimized. The Doppler waveforms were recorded on a magneto-optical disc for later analysis. In addition, to evaluate the relationship between mid-diastolic mitral annular motion patterns and stages of left ventricular diastolic dysfunction, we also categorized our study subjects according to mitral inflow filling patterns. The mitral inflow filling patterns were classified into three types as normal, abnormal relaxation and pseudo-normal/restrictive types on the basis of E/A, Ea and E/Ea. The normal filling pattern was recognized if E/A ratio was ⬎0.9, Ea ⬎8 cm/s and E/Ea ⬍10; abnormal relaxation filling pattern if E/A ratio was ⱕ0.9; and pseudo-normal/restrictive filling pattern if E/A ratio was ⬎0.9 and Ea ⱕ8 cm/s or E/Ea ⱖ10 (Bruch et al. 2000; Farias et al. 1999; Firstenberg et al. 2000; Garica et al. 1998; Khouri et al. 2004; Nagueh et al. 1997). Statistical analysis All data were expressed as mean (⫾ standard deviation). SPSS 11.0 (SPSS, Inc., Chicago, IL, USA) was used for statistical analysis. Multiple comparisons between the study groups were performed by one-way analysis of variance (ANOVA) followed by post hoc test adjusted with a Bonferroni correction. Categorical variables were compared by chi-square analyses. All tests were two-sided, and the level of significance was established as p ⬍ 0.05. RESULTS The clinical and echocardiographic characteristics among the study groups are shown in Table 1. The patients in group 1 were younger than those in groups 2 and 3 (both p ⬍ 0.001). The prevalence rate of diabetes mellitus and hypertension was lower in group 1 than in groups 2 and 3 (p ⱕ 0.026). The study was done with the patients taking their usual medications. Heart rate was not different among groups. Left atrial dimension (LA) and left ventricular end-diastolic
Mitral La wave and LV diastolic function ● H.-M. SU et al.
Fig 1. Doppler tissue images of the lateral mitral annulus from representative patients. Case A is a patient with apically-directed mid-diastolic annular motion (upward La wave) but without atrially-directed mid-diastolic annular motion (downward La wave) on each beat. Case B is a patient with alternating upward and downward La waves on each beat. Case C is a patient with downward, but not upward, La wave on each beat. Case D is a patient without La wave. Aa ⫽ late diastolic mitral annular velocity; Ea ⫽ early diastolic mitral annular velocity.
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Table 1. Distribution of various mitral inflow filling patterns in each group
Number (%) Age (y) Sex (M/F) Diabetes mellitus (%) Hypertension (%) Medications -blockers (%) CCBs (%) ACEIs (%) ARBs (%) Heart rate (beats/min) LA (mm) LVEDD (mm) LVESD (mm) E (cm/s) A (cm/s) E/A EDT (ms) Ea (cm/s) E/Ea Aa (cm/s) S (cm/s) IVRT (ms) EF (%)
Group 1
Group 2
Group 3
p
95 (47%) 50 ⫾ 16 44/51 10 34
37 (18%) 63 ⫾ 12* 19/18 24* 65*
71 (35%) 63 ⫾ 12* 41/30 34* 52*
⬍ 0.001 0.346 0.001 0.002
32 11 13 14 68 ⫾ 9 34 ⫾ 6 49 ⫾ 5 29 ⫾ 5 81 ⫾ 16 70 ⫾ 17 1.23 ⫾ 0.39 194 ⫾ 45 11.7 ⫾ 3.4 7.4 ⫾ 2.3 9.0 ⫾ 2.0 10.0 ⫾ 2.5 74 ⫾ 17 71 ⫾ 9
54 32 32 27 69 ⫾ 14 39 ⫾ 6* 54 ⫾ 8* 36 ⫾ 11* 82 ⫾ 24 83 ⫾ 24* 1.11 ⫾ 0.57 214 ⫾ 84 7.4 ⫾ 2.1* 11.6 ⫾ 4.2* 8.1 ⫾ 2.4 7.5 ⫾ 1.9* 86 ⫾ 19* 62 ⫾ 17*
32 28 20 28 72 ⫾ 11 36 ⫾ 6† 50 ⫾ 7† 31 ⫾ 8† 72 ⫾ 17*† 91 ⫾ 25* 0.83 ⫾ 0.28*† 229 ⫾ 70* 7.5 ⫾ 2.5* 10.6 ⫾ 4.4* 9.4 ⫾ 2.4† 7.9 ⫾ 2.2* 94 ⫾ 29* 67 ⫾ 12
0.059 ⬍ 0.001 ⬍ 0.001 ⬍ 0.001 0.002 ⬍ 0.001 ⬍ 0.001 0.002 ⬍ 0.001 ⬍ 0.001 0.019 ⬍ 0.001 ⬍ 0.001 ⬍ 0.001
A ⫽ peak late transmitral filling wave velocity; Aa ⫽ late diastolic velocity of lateral mitral annulus; ACEIs ⫽ angiotensin-converting enzyme inhibitors; ARBs ⫽ angiotensin II receptor antagonists; CCBs ⫽ calcium channel blockers; E ⫽ peak early transmitral filling wave velocity; Ea ⫽ early diastolic velocity of lateral mitral annulus; EDT ⫽ E-wave deceleration time; EF ⫽ ejection fraction; IVRT ⫽ isovolumic relaxation time; LA ⫽ left atrial dimension; LVEDD ⫽ left ventricular end-diastolic dimension; LVESD ⫽ left ventricular end-systolic dimension; S ⫽ systolic velocity of lateral mitral annulus. * 0.05 compared with group 1; † p ⬍ 0.05 compared with group 2.
and end-systolic dimensions (LVEDD and LVESD) were larger in group 2 than in groups 1 and 3 (p ⱕ 0.031). E and E/A were lower in group 3 than in groups 1 and 2 (p ⱕ 0.020). A was lower in group 1 than in groups 2 and 3 (p ⱕ 0.007). E-wave deceleration time (EDT) was longer in group 3 than in group 1 (p ⫽ 0.001). Ea and peak systolic mitral annular velocity (S) were higher, E/Ea was lower and isovolumic relaxation time (IVRT) was shorter in group 1 than in groups 2 and 3 (p ⱕ 0.014). Late diastolic mitral annular velocity (Aa) was lower in group 2 than in group 3 (p ⫽ 0.015). Left ventricular EF was lower in group 2 than in group 1 (p ⬍ 0.001). To exclude the influence of age on left ventricular diastolic function and filling pressure, we performed a subgroup analysis in 50 ⬍ patients ⱕ70 years old. In this subgroup analysis, age was not different among groups (p ⫽ 0.133). However, Ea was higher and E/Ea was lower in group 1 than in groups 2 and 3 (p ⱕ 0.044). To eliminate the influence of hypertension and diabetes mellitus on left ventricular diastolic function and filling pressure, we performed another subgroup analysis in the patients without these two diseases. Similarly, Ea was higher and E/Ea was lower in group 1 than in groups 2 and 3 (all p ⬍ 0.001). In addition, the third subgroup
analysis was performed in patients with left ventricular EF ⬎50% and, likewise, Ea was higher and E/Ea was lower in group 1 than in groups 2 and 3 (all p ⬍ 0.001), whereas left ventricular EF was not different among groups (p ⫽ 0.734). In our study, there were 14 patients (7%) with mitral L wave. Among them, there were nine patients (64%) with only downward La wave. In other words, in group 2 (n ⫽ 37), there were nine patients with mitral L wave but 28 patients without it. Besides, in group 2, the heart rate in nine patients with mitral L wave was slower than that in 28 patients without mitral L wave (59 ⫾ 9 vs. 72 ⫾ 13 beats/min, p ⫽ 0.013). Table 2 shows the distribution of various mitral inflow filling patterns in each group. In group 1, there were 71 (75%), 21 (22%) and 3 (3%) patients with
Table 2. Comparison of clinical and echocardiographic characteristics in study subjects Group 1 Group 2 Group 3 Normal filling pattern Abnormal relaxation filling pattern Pseudo-normal/restrictive filling pattern
71 21 3
5 15 17
8 47 16
Mitral La wave and LV diastolic function ● H.-M. SU et al.
normal, abnormal relaxation and pseudo-normal/restrictive filling patterns, respectively. The most common mitral inflow filling pattern in group 1 was normal filling pattern. In group 2, there were 5 (14%), 15 (41%) and 17 (46%) patients with normal, abnormal relaxation and pseudo-normal/restrictive filling patterns, respectively. Patients with abnormal mitral inflow filling patterns were more common than those with normal filling patterns in group 2 (p ⬍ 0.001). In group 3, there were 8 (11%), 47 (66%) and 16 (23%) patients with normal, abnormal relaxation and pseudo-normal/restrictive filling patterns, respectively. The most common mitral inflow filling pattern in group 3 was abnormal relaxation filling pattern (p ⬍ 0.001). The prevalence of upward La wave was 71 among the 84 patients with normal diastolic function (patients with normal filling pattern) and 24 among the 119 patients with abnormal diastolic function (patients with abnormal relaxation or pseudo-normal/restrictive filling pattern). Therefore, the sensitivity, specificity, positive and negative predictive values and accuracy of upward La wave in prediction of normal diastolic function were 85%, 80%, 75%, 88% and 82%, respectively. DISCUSSION Ea has been correlated with the time constant of left ventricular isovolumic pressure decrease (tau) and reported to be a noninvasive surrogate of myocardial relaxation (Sohn et al. 1997). E/Ea has been shown to be a good predictor of left ventricular filling pressure (Ommen et al. 2000). In this study, we found that Ea was higher and E/Ea was lower in group 1 than in groups 2 and 3. This finding suggested that patients with upward La wave may have better left ventricular relaxation function and lower left ventricular filling pressure than patients with only downward La wave and patients without La wave. Zaky et al. (1967) first noted that annular motion sometimes reverses direction after the initial Ea wave and may have clinical importance. Much later, Isaaz et al. (1993) described the continuous, alternating atrially and apically directed motion of the mitral annulus during the cardiac cycle and assumed that the balance between stored elastic potential energy and kinetic energy plays a role. Recently, Riordan and Kovács (2007) demonstrated that longitudinal annular motion during early and middiastolic filling as driven by strain energy stored during the previous systole and overshoots its equilibrium position and reverses direction (toward the apex) in certain subjects. They further found that patients with diastolic mitral annular oscillation had a shorter tau and IVRT, greater E/A and Ea and lower E/Ea than patients without diastolic mitral annular oscillation. Mitral annular mo-
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tion always overshoots its equilibrium position and reverses direction (toward apex) in the patients of group 1. Hence, the mitral annular motion in the patients of group 1 obeyed the mitral annular oscillation and, in compatibility with previous finding (Riordan and Kovács 2007), the patients in group 1 had shorter IVRT, greater Ea and lower E/Ea than the patients in the other groups. The patients in group 2 had only downward La wave. Mitral annular motion did not overshoot its equilibrium position but maintained in the downward direction (toward the left atrium). Hence, the mitral annular motion did not obey the diastolic mitral annular oscillation in the patients of group 2, so their left ventricular diastolic function was not as good as that in the patients of group 1. Ha et al. (2006) found that the presence of downward La wave in subjects with triphasic mitral inflow velocity pattern with mid-diastolic flow indicated advanced diastolic dysfunction and elevated left ventricular filling pressure. Although our study patients did not restrict to subjects with triphasic mitral inflow velocity pattern, the patients in group 2 similarly had more advanced diastolic dysfunction and higher left ventricular filling pressure than the patients in group 1. Riordan and Kovács (2007) found that the elastic strain energy was reduced and the resistance to left ventricular filling was increased in patients without diastolic mitral annular oscillation and showed that the absence of diastolic mitral annular oscillation was a marker for relation-related diastolic dysfunction. In our study, the patients in group 3 had neither upward nor downward La wave. Hence, there was no clear middiastolic mitral oscillation on three consecutive beats in the patients of group 3. In concordance with the finding of Riordan and Kovács (2007), the left ventricular diastolic function was worse and left ventricular filling pressure was higher in group 3 than in group 1. In addition, although the LA, LVEDD and LVESD were larger in the patients of group 2 than group 3, the Ea and E/Ea were similar between them. Hence, the diastolic function and left ventricular filling pressure were comparable in these two groups. Left ventricular diastolic function is known to depend on age (Nikitin et al. 2005). Because the patients in group 1 were younger than those in groups 2 and 3, the age difference may partially explain the better diastolic function and lower filling pressure in group 1. However, in the subgroup analysis involving the 50 ⬍ patients ⱕ70 years old, Ea was higher and E/Ea was lower in group 1 than in groups 2 and 3, whereas age was not different among groups. Therefore, age was not the major reason for better diastolic function and lower filling pressure in group 1. Hypertension and diabetes mellitus are reported to be detrimental to left ventricular diastolic function. In our study, these two diseases are less prevalent in group
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1 than in groups 2 and 3, so this difference in prevalence rate may cause the better diastolic function in group 1. However, after exclusion of subjects with these two diseases, Ea was also higher and E/Ea was also lower in group 1 than in groups 2 and 3. Hence, hypertension and diabetes mellitus were not the main cause of different diastolic function and filling pressure among groups. In addition, pathologic processes with cardiac involvement generally have an impact on the diastolic followed by systolic function of the ventricles. Thus, the patients with systolic function impairment are usually combined with advanced diastolic dysfunction. In our study, left ventricular systolic function was worse in group 2 than in groups 1 and 3; the difference in systolic function may confound our results. However, the subgroup analysis in patients with normal left ventricular systolic function showed that Ea was still higher and E/Ea was still lower in group 1 than in groups 2 and 3, whereas left ventricular EF was not different among groups. Consequently, left ventricular systolic function was also not the major reason of our findings. In a previous study by Lam et al. (2005), the mitral L wave was present in 20% of the patients. However, in another study by Ha et al. (2006), the mitral L wave was only present in 0.9% of the patients. In our study, the mitral L wave was present in 7% of the patients. In the study by Ha et al. (2004), Valsalva maneuver could abolish the mitral L wave in 59% of patients and leg elevation of the patient could produce the mitral L wave. Hence, preload has a pronounced effect on the development of mitral L wave. Slow heart rate was reported to be a prerequisite for the genesis of mitral L wave (Ha et al. 2004). Hence, the various heart rate and preload status may explain the diverse prevalence rates of mitral L wave among the different studies. In addition, in group 2, the heart rate in nine patients with mitral L wave was slower than that in 28 patients without mitral L wave. Therefore, the difference in heart rate may partially explain the presence or absence of mitral L wave in group 2. In patients with upward La wave, their longitudinal stored elastic strain, force and strain-energy were increased, suggesting the availability of more energy for myocardial recoil (Riordan and Kovács 2007). Hence, the relaxation function in patients with upward La wave should be good. This may explain that 75% of patients had normal mitral inflow filling pattern in group 1. However, there were still 25% of patients in group 1 showing abnormal physiology by mitral inflow filling pattern. Riordan and Kovács (2006) applied and validated damped simple harmonic oscillatory motion as the kinematic principle that governs mitral annular oscillations. These physics predict an oscillatory (stiffness ⬎ relaxation/viscoelasticity) regime for annular motion, as well as a nonoscillatory (stiffness ⬍ relaxation/viscoelastic-
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ity) regime. Hence, the presence of mitral annular oscillation is determined by multiple factors, not solely by relaxation function. This may explain why there were still 25% of patients in group 1 showing abnormal physiology by mitral inflow filling pattern. By contrast, in patients without upward La wave, their relaxation function may be impaired. This may explain that most of patients had abnormal mitral inflow filling patterns and only 14% and 11% of patients had normal filling pattern in groups 2 and 3. Therefore, upward La wave may be useful in predicting normal diastolic function. Increased heart rate can cause a decrease in the duration of diastasis (Chung and Kovács SJ 2006). Hence, higher heart rate may cause merging of Ea and Aa waves and preclude the identification of La wave. In our study, we did not exclude the subjects with higher heart rates. Therefore, patients in group 3 might shift to other groups if their heart rate decreased. However, in our study, heart rate was not different among groups and the highest heart rates in group 1, 2 and 3 were 109, 107 and 96 beats/min, respectively. Hence, La wave could be identified when heart rate was ⬎100 beats/min. Because the heart rates of patients in group 3 were all ⬍100 beats/min, the confounding effect of heart rate in identification of La wave in our study might be neglected. Study limitations In this study, we did not have invasive hemodynamic correlation of our findings. However, a study is underway to address this issue. In addition, we did not record mitral annular velocity pattern from various sites. Although the lateral annular velocity pattern is more reproducible than the septal one (Khoure et al. 2004) and it is echocardiographically easier to localize the sample volume at the lateral aspect and thereby minimize the likelihood of including myocardial tissue velocities, the analysis of annular velocity patterns from various sites may provide more information. In conclusion, patients with upward La wave had better left ventricular diastolic function and lower left ventricular filling pressure than patients without it. Upward La wave is useful in predicting normal diastolic function. Therefore, analysis of mid-diastolic mitral annular motion may be complementary to other measures of left ventricular diastolic function. REFERENCES Bruch C, Schmermund A, Bartel T, Schaar J, Erbel R. Tissue Doppler imaging: A new technique for assessment of pseudonormalization of the mitral inflow pattern. Echocardiography 2000;17:539 –546. Chung CS, Kovács SJ. Consequences of increasing heart rate on deceleration time, the velocity-time integral, and E/A. Am J Cardiol 2006;97:130 –136.
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