Mitral inflow patterns reflect not only left ventricular diastolic function but also left atrial (LA) remodeling. The aim of this study was to determine the effects of left ventricular diastolic dysfunction on LA volumetric and functional parameters assessed using two-dimensional speckle-tracking echocardiography.
Two-dimensional speckle-tracking analysis of the LA wall in the apical four-chamber view was performed in 268 subjects. Subjects were classified according to diastolic dysfunction grade. Indexed maximum and minimum LA volumes and indexed LA volume before atrial contraction were measured from LA volume waveforms. Expansion, passive emptying, and active emptying indices were calculated.
LA volumes increased progressively with advanced stages of diastolic dysfunction. The expansion index and passive emptying index showed progressive decreases according to the grade of diastolic dysfunction. The active emptying index increased until mild diastolic dysfunction and thereafter progressively decreased until reaching severe diastolic dysfunction. Significant correlations were noted between the active emptying index and A-wave velocity ( r = 0.31, P < .01) and between the E/E′ ratio and the expansion index ( r = 0.56, P < .01).
LA volumes and functional parameters derived from two-dimensional speckle-tracking echocardiography vary according to the level of diastolic dysfunction. These results suggest that left ventricular diastolic dysfunction also predicts the severity of LA remodeling.
Left ventricular (LV) diastolic function is frequently assessed using Doppler mitral inflow velocity patterns. In the earlier stages of LV diastolic dysfunction, the E-wave velocity is low because of delayed LV pressure decay. As LV filling pressure becomes elevated in the more advanced stages of LV diastolic dysfunction, left atrial (LA) pressure rises to maintain adequate LV filling, and subsequently, the E-wave velocity becomes higher than the A-wave velocity. Sustained elevated LA pressure results in LA remodeling, which is characterized by LA dilatation and impaired LA functional parameters. Accordingly, the mitral inflow patterns reflect not only LV diastolic function but also LA remodeling.
Several studies have reported that LA volumes and function reflect the severity of diastolic dysfunction. Two-dimensional (2D) speckle-tracking echocardiography (2DSTE) is a new modality that is capable of measuring phasic changes in LA volumes and strain. We have previously reported the feasibility and accuracy of measuring LA volumes using 2DSTE when assessing the effect of aging on LA function in healthy subjects. However, the effects of LV diastolic dysfunction on LA volumetric and functional indices derived from LA volume curves using 2DSTE have not been systematically studied. Accordingly, in this study, we sought to determine the effects of LV diastolic dysfunction grade on LA volumes and function assessed by 2DSTE.
The study group consisted of 268 subjects in normal sinus rhythm (mean age, 64 ± 12 years; 171 men), including 85 healthy subjects who were recruited from hospital employees and their relatives. All healthy subjects were aged > 40 years and did not have histories of hypertension, diabetes, and/or cardiovascular disease. None of the subjects were taking cardiac medications. In addition, 183 consecutive patients, who were referred for clinically indicated transthoracic echocardiography (iE33; Philips Medical Systems, Andover, MA), were studied. Exclusion criteria included inadequate image quality of the LA wall, presence of cardiac arrhythmias, mitral valvular disease, and rapid heart rates (usually >90 beats/min) resulting in fusion of the E and A waves. The institutional review board of the hospital approved the study, and all subjects provided written informed consent before participation.
Two-dimensional echocardiographic examinations were performed using a broadband transducer connected to a commercially available ultrasound machine (S5-1 probe, iE33). From the apical four-chamber and two-chamber views, LV end-diastolic and end-systolic volumes and ejection fraction were calculated using the biplane Simpson’s method. Each subject underwent pulsed-wave Doppler examination of mitral inflow obtained in the apical four-chamber view before and during the Valsalva maneuver. Pulmonary venous flow was also obtained. Doppler tissue imaging, used to measure septal mitral annular velocity, was performed by placing the sample volume in the septal corner of the mitral annulus in the apical four-chamber view. LV outflow tract velocities were obtained from the apical long-axis view. Isovolumic relaxation time was calculated as the time interval between aortic valve closure and mitral valve opening using mitral inflow and LV outflow tract velocities.
Assessment of LV Diastolic Function Grade
From mitral inflow velocities, the E-wave and A-wave velocities, E-wave deceleration time, and E/A velocity ratio were measured. Peak diastolic annular velocity during early diastolic rapid filling (E′) was also measured to calculate the E/E′ ratio in all subjects. All Doppler measurements were averaged from three consecutive beats.
LV diastolic function was categorized as normal, mild (defined as impaired relaxation without evidence of increased filling pressures), moderate (defined as impaired relaxation associated with moderate elevation of filling pressures or pseudonormal filling), or severe (defined as advanced reduction in compliance or reversible or fixed restrictive filling), as previously described by Redfield et al. ( Table 1 ). Subjects were required to meet at least two Doppler criteria consistent with mild, moderate, or severe diastolic dysfunction to be so classified. Subjects with one criterion for diastolic dysfunction or those whose parameters were borderline and suggestive of but not definitive of diastolic dysfunction were classified as indeterminate.
|Normal diastolic function||Mild diastolic dysfunction||Moderate diastolic dysfunction||Severe diastolic dysfunction|
|Mitral inflow||0.75 < E/A < 1.5, DcT > 140 msec||E/A ≤ 0.75||0.75 < E/A < 1.5, DcT > 140 msec||E/A > 1.5, DcT < 140 msec|
|Mitral inflow at peak Valsalva maneuver||ΔE/A < 0.5||ΔE/A < 0.5||ΔE/A ≥ 0.5|
|Doppler tissue imaging of mitral annular motion||E/E′ < 10||E/E′ < 10||E/E′ ≥ 10||E/E′ ≥ 10|
|Pulmonary venous flow||S ≥ D, ARdur < Adur||S > D, ARdur < Adur||S < D or ARdur > Adur + 30 msec||S < D or ARdur > Adur + 30 msec|
Assessment of LA Volume Curve Versus Time Using 2DSTE
Three consecutive beats were acquired in the apical four-chamber view (frame rate, 61 ± 14 frames/sec) using second harmonic mode. Two-dimensional endocardial tracking of the LA wall was performed using speckle-tracking software (QLAB version 7.0, TMQ; Philips Medical Systems). Initialization of the end-diastolic frame was completed with three points (septal and lateral corner of the mitral annulus and the roof of the left atrium). The software provides six tracking regions of interest on the LA wall and automatically performs speckle-tracking analysis in nine regions throughout the cardiac cycle. Manual adjustments of the LA tracking points were performed when required. LA volumes were calculated using the single-plane area-length formula. Computer-generated LA volume curves throughout the cardiac cycle were obtained, from which maximal and minimal LA volumes and LA volume before atrial contraction were measured. These values were indexed to body surface area (LAVImax, LAVImin, and LAVIpre-a, respectively).
Thereafter, the following LA emptying volume indices were calculated :
LA total emptying volume index = LAVImax − LAVImin,
LA passive emptying volume index = LAVImax − LAVIpre-a, and
LA active emptying volume index = LAVIpre-a − LAVImin.
LA reservoir function was assessed using two indices:
expansion index = [(LAVImax − LAVImin)/LAVImin] × 100, and
diastolic emptying index = [(LAVImax − LAVImin)/LAVImax] × 100.
LA conduit function was assessed using two indices:
passive emptying percentage of total emptying = [(LAVImax − LAVIpre-a)/(LAVImax − LAVImin)] × 100, and
passive emptying index = (LAVImax − LAVIpre-a)/LAVImax × 100.
Booster pump function was assessed using two indices:
active emptying percentage of total emptying = [(LAVIpre-a − LAVImin)/(LAVImax − LAVImin)] × 100, and
active emptying index = (LAVIpre-a − LAVImin)/LAVIpre-a × 100.
Continuous data are expressed as mean ± SD. In each subject, data points describing LA volume according to time were exported to spreadsheet software (Microsoft Excel; Microsoft Corporation, Redmond, WA) to calculate LA volume waveforms. To adjust for intersubject differences in heart rate, time sequences were normalized to the percentage of systolic duration (i.e., at end-systole, t was 100%) as well as diastolic duration (i.e., at end-diastole, t was 100%). Data were analyzed using analysis of variance with post hoc analysis of Bonferroni’s correction between diastolic dysfunction grade groups. Also, linear or polynomial regression analysis was performed to determine LA functional indices and traditional diastolic parameters. A P value < .05 was considered significant. Intraobserver and interobserver variability for the LA volume measurements using 2DSTE (8%-13% and 9%-14%, respectively) were reported in our previous study.
Clinical characteristics and standard echocardiographic findings are shown in Table 2 . Diastolic function was classified as normal or abnormal in 208 subjects (78%) and as indeterminate in 60 participants (22%). Among the 60 with indeterminate diastolic dysfunction, 53 had E/A ratios < 0.75 but E/E′ ratios > 10. Among the 183 patients, the clinical diagnoses included ischemic heart disease ( n = 72), hypertensive heart disease ( n = 29), hypertrophic cardiomyopathy ( n = 9), dilated cardiomyopathy ( n = 18), aortic valve disease ( n = 20), and a variety of other cardiac abnormalities ( n = 35).
|Variable||( n = 77)||( n = 30)||( n = 71)||( n = 30)||P (ANOVA)|
|Age (y)||57 ± 10||67 ± 10||69 ± 11||64 ± 13||<.001|
|HR (beats/min)||63 ± 8||68 ± 10||63 ± 11||72 ± 12||<.001|
|SBP (mm Hg)||127 ± 14||139 ± 22||141 ± 26||133 ± 32||<.05|
|DBP (mm Hg)||78 ± 11||81 ± 12||77 ± 14||78 ± 21||NS|
|IVRT (msec)||75 ± 24||107 ± 34||108 ± 32||79 ± 31||<.001|
|E velocity (cm/sec)||71 ± 13||49 ± 12||87 ± 25||103 ± 18||<.001|
|A velocity (cm/sec)||63 ± 14||77 ± 15||89 ± 29||43 ± 12||<.001|
|E/A ratio||1.2 ± 0.2||0.6 ± 0.1||1.1 ± 0.2||2.5 ± 0.7||<.001|
|DcT (msec)||195 ± 37||263 ± 80||226 ± 63||124 ± 13||<.001|
|E′ (cm/sec)||8.1 ± 1.6||6.0 ± 1.7||4.7 ± 1.2||4.7 ± 1.3||<.001|
|A′ (cm/sec)||9.5 ± 1.7||9.1 ± 1.7||7.4 ± 1.9||5.1 ± 1.6||<.001|
|E/E′ ratio (cm/sec)||8.9 ± 1.6||8.3 ± 1.1||20.0 ± 8.1||23.5 ± 8.1||<.001|
|LVEDVI (mL/m 2 )||54 ± 13||56 ± 26||85 ± 35||102 ± 36||<.001|
|LVESVI (mL/m 2 )||22 ± 8||28 ± 26||49 ± 32||74 ± 37||<.001|
|LVEF (%)||60 ± 7||55 ± 15||46 ± 15||31 ± 16||<.001|
The isovolumic relaxation time was prolonged from normal in patients with mild diastolic dysfunction but did not show progressive prolongation as the severity of diastolic dysfunction increased to moderate and severe. The E/E′ ratio increased with the severity of diastolic dysfunction. LV volumes also increased with the severity of diastolic dysfunction, whereas LV ejection fraction progressively decreased.
Adequate speckle tracking of the LA wall was obtained in all subjects. Figure 1 depicts LA volume curves acquired during one cardiac cycle in two representative patients with different grades of diastolic dysfunction. Figure 2 depicts average LA volume waveforms for each grade of diastolic dysfunction severity. In addition to the LA volumes, the contribution of passive filling and atrial contraction in each group can be appreciated. Table 3 depicts the LA volumes and the respective LA parameters obtained from LA volume curves among the four groups of normal or abnormal diastolic dysfunction. Although LAVImax, LAVImin, and LAVIpre-a were increased significantly in parallel with the severity of diastolic dysfunction, the magnitude of increase in LAVImin was greater that the increase in LAVImax with worsening diastolic dysfunction. The passive emptying volume index was significantly lower in the mild diastolic dysfunction group compared with the normal diastolic function group. The active emptying volume index increased until moderate diastolic dysfunction and then declined with severe diastolic dysfunction.
|Variable||( n = 77)||( n = 30)||( n = 71)||( n = 30)||P (ANOVA)|
|LAVImax (mL/m 2 )||27.0 ± 7.6||27.3 ± 7.7||52.4 ± 17.4||66.3 ± 22.8||<.001|
|LAVImin (mL/m 2 )||14.4 ± 4.5||16.1 ± 5.3||36.5 ± 14.8||54.0 ± 19.6||<.001|
|LAVIpre-a (mL/m 2 )||19.5 ± 5.7||22.2 ± 6.7||44.2 ± 15.6||58.7 ± 20.2||<.001|
|TEVI (mL/m 2 )||12.7 ± 3.9||11.2 ± 3.8||15.9 ± 6.0||12.4 ± 5.0||<.001|
|PEI (mL/m 2 )||7.5 ± 2.9||5.2 ± 2.6||8.2 ± 4.2||7.6 ± 4.9||<.005|
|AEI (mL/m 2 )||5.1 ± 1.8||6.1 ± 2.2||7.6 ± 3.2||4.8 ± 2.2||<.001|
|Expansion index (%)||91.0 ± 25.7||74.5 ± 25.2||49.4 ± 23.8||24.5 ± 11.2||<.001|
|Diastolic emptying index||46.8 ± 6.7||41.6 ± 8.1||31.5 ± 10.1||19.1 ± 6.7||<.001|
|PE (%)||58.6 ± 9.8||45.3 ± 13.4||51.2 ± 13.4||58.2 ± 20.8||<.001|
|PEI (%)||27.6 ± 7.0||19.3 ± 7.9||16.1 ± 6.6||11.3 ± 6.0||<.001|
|AE (%)||41.4 ± 9.8||54.7 ± 13.4||48.8 ± 13.4||41.8 ± 20.8||<.001|
|AEI (%)||19.1 ± 4.5||22.3 ± 5.3||15.4 ± 6.0||7.8 ± 4.4||<.001|