- Email: [email protected]
Clinical Application of Pulsed Doppler Tissue Imaging for Assessing Abnormal Left Ventricular Relaxation
Clinical Application of Pulsed Doppler Tissue Imaging for Assessing Abnormal Left Ventricular Relaxation Takashi Oki, MD, Tomotsugu Tabata, MD, Hirotsugu Yamada, MD, Tetsuzo Wakatsuki, MD, Hisanori Shinohara, MD, Akiyoshi Nishikado, Arata Iuchi, MD, Nobuo Fukuda, MD, and Susumu Ito, MD
MD,
Conventional assessment of left ventricular (LV) relaxation by calculating the time constant of LV pressure decay during the isovolumic diastole requires an invasive approach. Conversely, noninvasive parameters obtained by measuring isovolumic relaxation time and transmitral flow velocity often give inaccurate information. Using LV pressure curve, pulsed Doppler echocardiography, and pulsed Doppler tissue imaging in 38 patients with heart disease and 12 control subjects, we calculated the time constant and recorded transmitral flow velocity and motion velocities at the endocardial portions of the ventricular septum and LV posterior wall. Compared with the controls, patients exhibited a prolonged time constant, a decreased peak early diastolic velocity of the LV posterior wall, and a prolonged time interval from the second heart sound to the peak of the
early diastolic wave. The time constant correlated well with the isovolumic relaxation time and various parameters calculated from the transmitral flow velocity, except in patients with elevated LV end-diastolic pressure. In all subjects, the time constant correlated negatively with the peak early diastolic velocity of the posterior wall and positively with the time from the second heart sound to the peak of the early diastolic wave. Thus, early diastolic parameters derived from the motion velocity of the LV posterior wall by pulsed Doppler tissue imaging were closely related to the time constant. This technique may allow noninvasive evaluation of abnormal LV relaxation in patients with various heart diseases. Q1997 by Excerpta Medica, Inc. (Am J Cardiol 1997;79:921–928)
eft ventricular (LV) diastolic dysfunction usually precedes systolic dysfunction, L and abnormal relaxation is observed at its earliest stage. Con-
by pulsed Doppler tissue imaging for accurate evaluation of abnormal LV relaxation in patients with various heart diseases.
1–3
2–4
ventional clinical evaluation of LV relaxation involves determining the time constant of pressure decay during isovolumic diastole as calculated from the LV pressure curve.5 However, an invasive procedure is required to determine this parameter. There have been numerous attempts to use noninvasive methods to assess abnormal LV relaxation.6 – 8 These efforts have been hampered by the fact that abnormal LV relaxation often is masked in patients with strongly elevated left atrial pressure.9 – 11 Thus, it can be difficult to determine accurately the ventricular relaxation in patients with various hemodynamic backgrounds.4,12,13 Recently, a Doppler tissue imaging method has been developed in which large Doppler signals obtained from the ventricular wall can be selectively displayed as a color or pulsed Doppler image by eliminating small Doppler signals produced by the blood flow. This new technique is expected to produce valuable information on LV motion abnormalities in patients with heart disease.14 – 17 This study examines the usefulness of parameters obtained from the LV wall motion velocity as measured From the Second Department of Internal Medicine, Tokushima University School of Medicine, Tokushima, Japan and the Institute for Clinical Research, Zentsuji National Hospital, Zentsuji, Kagawa, Japan. Manuscript received August 5, 1996; revised manuscript received and accepted November 5, 1996. Address for reprints: Takashi Oki, MD, The Second Department of Internal Medicine, Tokushima University School of Medicine, 2-50 Kuramoto-cho, Tokushima 770, Japan.
METHODS Study population: We performed routine echocardiography, left cardiac catheterization, and coronary angiography in 100 consecutive Japanese patients with suspected cardiovascular disease based on clinical symptoms such as chest pain and dyspnea, abnormal findings in the electrocardiogram, cardiomegaly in the chest radiograph, and heart murmurs during auscultation. In 50 (32 men and 18 women, age range 39 to 72 years, mean 54 { 9) of the 100 patients, LV pressure curves were recorded using a high-fidelity manometer-tipped catheter. Pulsed Doppler echocardiography and Doppler tissue imaging were performed immediately before or simultaneously during cardiac catheterization. The examined subjects included those with ischemic heart disease (20 patients), hypertensive heart disease (8 patients), dilated cardiomyopathy (7 patients), cardiac amyloidosis (3 patients), and, as controls, 12 with the chest pain syndrome. The latter 12 subjects showed no significant cardiovascular disease by routine echocardiography and cardiac catheterization, including coronary angiography. Of the 20 patients with ischemic heart disease, 9 experienced no chest pain and, at rest, exhibited neither regional asynergy of the LV wall nor LV systolic dysfunction, although significant stenosis of 75% or more was observed in at least 1 branch of the coronary arteries, excluding the left anterior de-
Q1997 by Excerpta Medica, Inc.
0002-9149/97/$17.00 PII S0002-9149(97)00015-5
All rights reserved.
/ 2w1e 0887 Mp
921
Friday Mar 14 12:48 PM
EL–AJC (v. 79, no. 7 ’97)
0887
921
tion, however, was performed at a time when creatinine kinase values had returned to normal and LV asynergy was detected only between the anterior wall and the ventricular septum (systolic amplitudes of the LV wall motion measured from M-mode echogram; ventricular septum 0.1 { 2.6 mm, posterior wall 13.4 { 2.5 mm). The remaining 3 patients had lesions in the 3 branches of the coronary artery, diffuse asynergy of the LV wall, and signs of ischemic cardiomyFIGURE 1. Simultaneous recordings of the left ventricular pressure (LVP) curve and motion opathy (ß25% fractional shortening of the LV by M-mode velocity patterns of the ventricular septum (IVS; left ) and posterior wall (PW; right ) measured by pulsed Doppler tissue imaging. dP/dt Å first derivative of LV pressure curve; Ew echocardiography).18 Å peak early diastolic velocity of the LV wall; IIA-Ew Å time from the aortic component of All 8 patients with hypertenthe second heart sound to the peak of the early diastolic wave of the LV wall; ECG Å sive heart disease had a history of electrocardiogram; PCG Å phonocardiogram. hypertension for ú5 years, and their blood pressure was controlled by recent medical treatment. None of these patients showed abnormal LV wall motion, although 4 patients had symmetric hypertrophy of the LV wall of ¢12 mm as determined by M-mode echocardiography. The 7 patients with dilated cardiomyopathy showed no signs of significant stenosis or obstruction of the coronary artery; however, LV dilation (enddiastolic dimension by M-mode echocardiography ®6.0 cm) and diffuse asynergy of the LV wall (ß25% fractional shortening) were observed. All 3 patients with cardiac amyloidosis were positive for amyloid in the myocardial or rectal tissue, as determined by Congo-red staining. M-mode echocardiography detected symmetric hypertrophy of the LV wall of ¢12 mm and LV systolic dysfunction (ß30% fractional shortening). Mitral regurgitation was detected in 8 patients with coronary artery disease, 4 patients with dilated cardiomyopathy, and 2 patients with cardiac amyFIGURE 2. Measurement of variables obtained from the early diloidosis. According to Seller et al’s19 classification astolic wave of the transmitral flow velocity by pulsed Doppler by left ventriculography, its severity was õ2/ in all echocardiography. A Å atrial systolic wave; AC Å acceleration of the early diastolic wave; AT Å acceleration time from the start patients. of the early diastolic flow to the peak of the early diastolic wave; The objective of the examinations was explained DC Å deceleration of the early diastolic wave; DT Å deceleration to, and informed consent was obtained from each time from the peak of the early diastolic wave to the end of the subject. early diastolic flow; E Å peak velocity of the early diastolic wave; IRT Å time from the aortic component of the second heart Study protocol: CARDIAC CATHETERIZATION: In all sound (IIA) to the start of the early diastolic flow; other abbreviapatients, the LV pressure curve, its first derivative tions as in Figure 1. (dP/dt), the phonocardiogram, and the electrocardiogram were simultaneously recorded on paper at 50 scending branch. Another 3 patients had effort an- or 100 mm/s using a standard percutaneous femoral gina with significant stenosis of 75% or more in at approach and a 7F high-fidelity manometer-tipped least 1 of the coronary artery branches, excluding the catheter (Figure 1). Although the time constant of left anterior descending branch. These patients were LV pressure decay during isovolumic diastole has examined in the absence of an attack when asynergy largely been calculated assuming a zero asymptote of the LV wall and LV systolic dysfunction were by means of nonlinear least-squares parameter estiabsent. In 5 patients, complete obstruction of seg- mation,13 we used the method of Weiss et al5 in this ment 6 or 7 of the left anterior descending coronary study. The LV end-diastolic pressure also was meaartery had been observed during emergency coro- sured just before coronary angiography and left vennary angiography at the acute phase. Our examina- triculography. 922
THE AMERICAN JOURNAL OF CARDIOLOGYT
/ 2w1e 0887 Mp
922
VOL. 79
Friday Mar 14 12:48 PM
APRIL 1, 1997
EL–AJC (v. 79, no. 7 ’97)
0887
umes were set at the endocardial portions of the basilar, middle, and apical sites of both LV walls (i.e., ventricular septum and posterior wall). The motion velocity patterns at each site were recorded by the pulsed Doppler method using a Toshiba SSA-380A instrument (Figure 3). From the obtained patterns, the peak early diastolic velocities and the times from the aortic component of the second heart sound to the peak of the early diastolic wave of both the LV walls were determined (Figure 1). Statistical analysis: Values are expressed as means { SD. Mean values in different patient groups and at each site of the ventricular septum and posterior wall were compared by analyses of variance and covariance, respectively, and the unpaired Scheffe’s test. Linear regression coefficients were obtained to show the degree of correlation among variables. A p level õ0.05 was considered statistically significant.
RESULTS FIGURE 3. Sample recording of the motion velocity patterns of the ventricular septum (IVS) and posterior wall (PW) by pulsed Doppler tissue imaging in the parasternal long-axis view of the left ventricle. Sample volumes (white circles) were set at the endocardial portions of the basilar (B), middle (M), and apical (A) sites of the ventricular septum and posterior wall. Ao Å ascending aorta; LA Å left atrium; RV Å right ventricle; LV Å left ventricle. PULSED DOPPLER ECHOCARDIOGRAPHY: A sample volume was set at the mitral valve orifice in the longaxis view of the left ventricle or the 4-chamber view recorded from the cardiac apex, and transmitral flow velocity patterns were recorded using a commercially available Toshiba SSA-380A (Toshiba Corporation, Tokyo, Japan; 3.75-MHz probe). From the obtained early diastolic wave, the peak velocity, acceleration, acceleration time from the start of the early diastolic flow to the peak of the early diastolic wave, deceleration, and deceleration time from the peak of the early diastolic wave to the end of the early diastolic flow were determined (Figure 2). The isovolumic relaxation time was determined as the time from the aortic component of the second heart sound to the start of the early diastolic flow. DOPPLER TISSUE IMAGING: In the parasternal longaxis echocardiogram of the left ventricle, sample vol-
Clinical data: The group of patients with heart disease and the control group did not differ significantly as to age or heart rate (Table I). The 38 patients were classified into 2 groups with respect to transmitral flow velocity patterns. Nine patients (5 with dilated cardiomyopathy, 2 with ischemic cardiomyopathy, and 2 with cardiac amyloidosis) exhibited a pseudonormalized pattern; that is, the ratio of the peak velocity of the atrial systolic wave to the peak velocity of the early diastolic wave (A/E) was õ1. The remaining 29 patients demonstrated a decrease in the peak early diastolic velocity and a compensatory increase in the peak atrial systolic velocity (A/E ®1). This group included 5 patients with anterior myocardial infarction. The 9 patients with a pseudonormalized transmitral flow velocity had a significantly lower systolic blood pressure than the other patients and the control group. Time constant and left ventricular end-diastolic pressure: The time constant of LV pressure decay during
an isovolumic diastole was significantly or slightly prolonged in the 3 patient groups compared with the control group (Table I). The increase in the time constant was greatest in the A/E õ1 group. The LV enddiastolic pressure in the patients with A/E õ1 was significantly higher than in the controls or in the A/E ®1 group. In patients with anterior myocardial
TABLE I Clinical Data and Hemodynamic Variables Group Control Patients A/E ¢1 A/E õ1 Anterior MI
No. of Cases
Age (yr)
Heart Rate (beats/min)
SBP (mm Hg)
DBP (mm Hg)
Tau (ms)
12
56 { 17
72 { 10
128 { 20
70 { 15
39 { 2
24 9 5
62 { 10 58 { 8 60 { 4
70 { 8 74 { 11 69 { 7
130 { 14 110 { 18*,§ 121 { 13
83 { 9† 62 { 6x 73 { 10x,Ø
50 { 9† 63 { 6‡,§ 50 { 4#
LVEDP (mm Hg) 9{4 12 { 7 19 { 5‡,§ 14 { 5*
*p õ0.05 vs control group; †p õ0.01 vs control group; ‡p õ0.001 vs control group; §p õ0.01 vs A/E ¢1 group; xp õ0.001 vs A/E ¢1 group; Øp õ0.05 vs A/E õ1 group; #p õ0.001 vs A/E õ1 group. A/E Å peak velocity ratio of the atrial systolic to the early diastolic wave in the transmitral flow; DBP Å diastolic blood pressure; LVEDP Å left ventricular enddiastolic pressure; MI Å myocardial infarction; SBP Å systolic blood pressure; Tau Å time constant calculated from the left ventricular pressure decay at isovolumic diastole.
METHODS/DOPPLER TISSUE IMAGING TO ASSESS LV RELAXATION
/ 2w1e 0887 Mp
923
Friday Mar 14 12:48 PM
EL–AJC (v. 79, no. 7 ’97)
0887
923
TABLE II Variables Derived from Transmitral Flow Velocity IRT (ms)
Group Control (n Å 12) Patients (n Å 38) A/E ¢1 (n Å 24) A/E õ1 (n Å 9) Anterior MI (n Å 5)
E-AC (mm/s2)
E-AT (ms)
75 { 6
751 { 70
87 { 10
87 { 18* 69 { 7‡ 86 { 11*,Ø
515 { 175† 772 { 122§ 520 { 37*,**
111 { 22† 89 { 11‡ 106 { 12Ø
E-DC (mm/s2)
E-DT (ms)
E (cm/s)
485 { 139
169 { 50
69.9 { 8.6
357 { 206 771 { 139†,x 361 { 85††
206 { 60 103 { 24*,x 162 { 31#
53.4 { 12.7† 83.5 { 22.4x 55.8 { 9.8Ø
*p õ0.05 vs control group; †p õ0.01 vs control group; ‡p õ0.05 vs A/E ¢1 group; §p õ0.01 vs A/E ¢1 group; xp õ0.001 vs A/E ¢1 group; Øp õ0.05 vs A/E õ1 group; #p õ0.01 vs A/E õ1 group; **p õ0.001 vs A/E õ1 group; ††p õ0.0001 vs A/E õ1 group. A/E Å peak velocity ratio of the atrial systolic to the early diastolic wave in the transmitral flow; E Å peak velocity of the early diastolic wave; E-AC Å acceleration of the early diastolic wave; E-AT Å acceleration time from the start of the early diastolic flow to the peak of the early diastolic wave; E-DC Å deceleration of the early diastolic wave; E-DT Å deceleration time from the peak of the early diastolic wave to the end of the early diastolic flow; IRT Å time from the aortic component of the second heart sound (IIA) to the start of the early diastolic flow; MI Å myocardial infarction.
FIGURE 4. Correlations between the time constant (Tau) and the isovolumic relaxation time and variables of the early diastolic wave of transmitral flow velocity. A/E Å peak velocity ratio of the atrial systolic to the early diastolic wave in the transmitral flow; E Å peak velocity of the early diastolic wave; E-AC Å acceleration of the early diastolic wave; E-AT Å acceleration time from the start of the early diastolic flow to the peak of the early diastolic wave; E-DC Å deceleration of the early diastolic wave; E-DT Å deceleration time from the peak of the early diastolic wave to the end of the early diastolic flow; MI Å myocardial infarction; other abbreviations as in Figure 2.
infarction, the LV end-diastolic pressure tended to be elevated compared with the control group but did not differ significantly from the A/E ®1 group. Transmitral flow velocity: Determination of the transmitral flow velocity in the 4 experimental groups allowed calculation of several relevant variables. The isovolumic relaxation times in the patients with A/E ®1 or with anterior myocardial infarction were increased significantly compared with the control group (Table II). In contrast, patients with A/E 924
THE AMERICAN JOURNAL OF CARDIOLOGYT
/ 2w1e 0887 Mp
924
VOL. 79
Friday Mar 14 12:48 PM
õ1 had a significantly shorter isovolumic relaxation time than the A/E ®1 group, but did not differ significantly from the control group. The A/E ®1 group had a significantly prolonged acceleration time of the early diastolic wave and a significantly decreased acceleration and peak velocity of the early diastolic wave compared with the control group. The A/E õ1 group, in contrast, was characterized by significant decreases in the acceleration time and deceleration time of the early diaAPRIL 1, 1997
EL–AJC (v. 79, no. 7 ’97)
0887
Ew (cm/s)
129 { 14
IIA-Ew (ms)
3.4 { 1.2
4.8 { 1.5
4.3 { 1.2
Ew (cm/s)
179 { 18*
162 { 21
171 { 30†
16.4 { 1.0§,#
5.4 { 1.2‡,§
TABLE III Variables Derived from Pulsed Doppler Tissue Imaging
6.6 { 1.2
165 { 39*
3.4 { 1.8
160 { 11‡
138 { 30*
14.7 { 0.9Ø,#
5.0 { 0.7‡,x
8.0 { 2.8‡
120 { 5§,#
159 { 12†
139 { 36
Ew (cm/s) IIA-Ew (ms)
111 { 6
Ew (cm/s)
13.8 { 1.2
IIA-Ew (ms)
114 { 5
PW (apical)
9.7 { 3.2‡
102 { 7§,#
PW (middle)
Ew (cm/s)
112 { 5
4.9 { 1.0‡,Ø
IIA-Ew (ms)
IIA-Ew (ms)
15.0 { 1.4
133 { 30
15.8 { 0.9Ø,#
14.7 { 1.4
133 { 14
10.9 { 3.8*
159 { 12†,§
105 { 6#
PW (basilar)
IIA-Ew (ms)
5.5 { 1.4
175 { 18*
158 { 19
IVS (apical)
128 { 15
3.8 { 1.0†,§
IVS (middle)
155 { 38
3.8 { 1.7*
IVS (basilar)
6.8 { 1.3
166 { 14*
Ew (cm/s)
6.1 { 2.7
174 { 18*
Group
A/E ®1 (n Å 24)
4.0 { 2.0
3.7 { 0.8*,§
Control (n Å 12)
A/E õ1 (n Å 9)
Patients (n Å 38)
Anterior MI (n Å 5)
*p õ0.05 vs control group; †p õ0.01 vs control group; ‡p õ0.001 vs control group; §p õ0.05 vs A/E ®1 group; xp õ0.01 vs A/E ®1 group; Øp õ0.001 vs A/E ®1 group; #p õ0.0001 vs A/E õ1 group.
A/E Å peak velocity ratio of the atrial systolic to the early diastolic wave in the transmitral flow; Ew Å peak early diastolic velocity of the left ventricular wall; IVS Å interventricular septum; MI Å myocardial infarction; PW Å left ventricular
posterior wall; IIA-Ew Å time from the aortic component of the second heart sound to the peak of the early diastolic wave of the left ventricular wall.
stolic wave, as well as by significant increases in acceleration, deceleration, and peak velocity of the early diastolic wave compared with the A/E ®1 group. There were no significant differences in isovolumic relaxation time, acceleration, acceleration time, and peak velocity of the early diastolic wave between the A/E õ1 and control groups. In all subjects, the time constant was weakly correlated with isovolumic relaxation time (r Å 0.32, p õ0.05), acceleration of the early diastolic wave (r Å 00.32, p õ0.05), and acceleration time of the early diastolic wave (r Å 0.36, p õ0.05) (Figure 4). When the 9 patients of the A/E õ1 group were excluded from this analysis, a strong correlation existed between the time constant and the isovolumic relaxation time (r Å 0.77, p õ0.0001), acceleration of the early diastolic wave (r Å 00.83, p õ0.0001), and acceleration time of the early diastolic wave (r Å 0.88, p õ0.0001). No significant correlations existed between the time constant and the deceleration, deceleration time, and peak velocity of the early diastolic wave. Left ventricular wall motion velocity: Pulsed Doppler tissue imaging demonstrated that in all subjects the peak early diastolic velocities of the ventricular septum and posterior wall decreased gradually between the basilar and apical sites, whereas the time from the second heart sound to the peak of the early diastolic wave increased gradually (Table III). Moreover, the peak early diastolic velocity at each site of the ventricular septum was significantly lower than at the corresponding sites of the posterior wall (p õ0.01, p õ0.001, or p õ0.0001 for the basilar, middle, and apical sites) except for the A/E õ1 group. In contrast, the time from the second heart sound to the peak of the early diastolic wave was significantly longer at the ventricular septum than at the posterior wall in all experimental groups (p õ0.01, p õ0.001, or p õ0.0001 for the basilar, middle, and apical sites) except for the A/E õ1 group. Furthermore, in the patients with A/E õ1, the peak early diastolic velocity at the basilar and middle portions of the ventricular septum was significantly lower than in the control and A/E ®1 groups. In the patients with anterior myocardial infarction, the peak early diastolic velocity at the middle site of the ventricular septum was significantly reduced compared with the control group. At the posterior wall, peak early diastolic velocities at all 3 sites were significantly lower in the A/E ®1 and A/E õ1 groups than in the control group, whereas the time from the second heart sound to the peak of the early diastolic wave was significantly or slightly prolonged. In the anterior myocardial infarction group, the peak early diastolic velocity was significantly greater and the time from the second heart sound to the peak of the early diastolic wave was significantly or slightly decreased at the basilar to apical sites of the posterior wall compared with the A/E ®1 and A/E õ1 groups.
METHODS/DOPPLER TISSUE IMAGING TO ASSESS LV RELAXATION
/ 2w1e 0887 Mp
925
Friday Mar 14 12:48 PM
EL–AJC (v. 79, no. 7 ’97)
0887
925
FIGURE 5. Correlations between the time constant (Tau) and the peak early diastolic velocity and time from the aortic component of the second heart sound to the peak of the early diastolic wave measured by pulsed Doppler tissue imaging method at each site of the ventricular septum. IVS-B-Ew; IVS-M-Ew, and IVS-A-Ew Å peak early diastolic velocity at the basilar, middle, and apical sites of the ventricular septum, respectively; IVS-B-(IIA-Ew), IVS-M-(IIA-Ew), and IVS-A-(IIA-Ew) Å time from the aortic component of the second heart sound to the peak of the early diastolic wave at the basilar, middle, and apical sites of the ventricular septum, respectively; MI Å myocardial infarction; other abbreviations as in Figures 2 to 4.
The time constants in all 50 subjects were negatively correlated with the peak early diastolic velocities at the basilar and middle sites of the ventricular septum (r Å 00.34, p õ0.05; r Å 00.46, p õ0.01, respectively) (Figure 5, top), and positively correlated with the time from the second heart sound to the peak of the early diastolic wave at the middle and apical sites of the ventricular septum (r Å 0.29, p õ0.05; r Å 0.47, p õ0.001, respectively) (Figure 5, bottom). However, no significant correlations between these parameters existed at the other sites of the ventricular septum. At all sites of the posterior wall, on the other hand, the time constant was strongly and negatively correlated with the peak early diastolic velocity (basilar: r Å 00.81, p õ0.0001; middle: r Å 00.78, p õ0.0001; apical: r Å 00.69, p õ0.0001) (Figure 6, top), and strongly and positively correlated with the time from the second heart sound to the peak of the early diastolic wave (basilar: r Å 0.80, p õ0.0001; middle: r Å 0.81, p õ0.0001; apical: r Å 0.71, p õ0.0001) (Figure 6, bottom). In this analysis, the 5 patients with anterior myocardial infarction were unique in that they had a higherthan-average peak early diastolic velocity and a shorter-than-average time from the second heart 926
THE AMERICAN JOURNAL OF CARDIOLOGYT
/ 2w1e 0887 Mp
926
VOL. 79
Friday Mar 14 12:48 PM
sound to the peak of the early diastolic wave at all 3 sites of the posterior wall.
DISCUSSION To evaluate the diastolic function of the LV accurately, it is necessary to assess LV relaxation at the isovolumic diastole as well as LV filling, which, in turn, is determined by the relationship between LV volume and pressure after opening of the mitral valve.1 LV relaxation abnormalities sometimes appear before the occurrence of LV systolic dysfunction.1 – 3 Moreover, these abnormalities have been reported to develop with age even in healthy subjects.20,21 The time constant calculated from the pressure decay during early diastole in the LV pressure curve is well known as a parameter assessing LV relaxation abnormalities.5 This method is rarely used, however, because it requires invasive measurements. More recently, several studies have used the increasingly popular pulsed and continuous wave Doppler echocardiographic approach to detect LV relaxation abnormalities noninvasively. For instance, isovolumic relaxation time can be determined by measuring the time from the aortic component of the second heart sound to the opening of the mitral APRIL 1, 1997
EL–AJC (v. 79, no. 7 ’97)
0887
FIGURE 6. Correlations between the time constant (Tau) and the peak early diastolic velocity and time from the aortic component of the second heart sound to the peak of the early diastolic wave measured by pulsed Doppler tissue imaging method at each site of the posterior wall. PW-B-Ew, PW-M-Ew, and PW-A-Ew Å peak early diastolic velocity at the basilar, middle, and apical sites of the posterior wall, respectively; PW-B-(IIA-Ew), PW-M-(IIA-Ew), and PW-A-(IIA-Ew) Å time from the aortic component of the second heart sound to the peak of the early diastolic wave at the basilar, middle, and apical sites of the posterior wall, respectively; MI Å myocardial infarction.
valve.6,7,22,23 Many other parameters—such as peak velocity, acceleration, deceleration, acceleration time, and deceleration time of the early diastolic wave—can be determined from the transmitral flow velocity.8,11 However, these parameters are influenced strongly by aortic or left atrial pressure.4,12,13 In patients with significantly elevated left atrial pressure or with restrictive physiology, the transmitral flow velocity shows pseudonormalization.9 – 11 In these cases, the isovolumic relaxation time and the parameters obtained from the early diastolic wave frequently appear almost normal, despite an increase in the time constant. These observations, as well as our results in this study, indicate that the parameters of the early diastolic wave or isovolumic relaxation time correlate with the time constant only under a certain level of preload increase. Beyond this level, these parameters cannot be used to evaluate LV relaxation abnormalities. Other studies have attempted to evaluate LV relaxation abnormalities associated with various heart diseases using early diastolic envelopes of the mitral and aortic regurgitant velocity patterns obtained from continuous wave Doppler echocardiography.24–26 The relaxation parameters obtained by this method correlated closely with the time constant calculated
from the LV pressure curve, indicating that it can aid in noninvasively evaluating LV relaxation abnormalities. However, this method is applicable only to patients with complications from mitral or aortic regurgitation and requires a complete and clear recording of the envelopes of the regurgitant velocity patterns. A method of Doppler tissue imaging has been developed to measure the motion velocity in myocardial tissue. This method has been used to evaluate the ventricular wall motion velocity quantitatively in patients with various kinds of heart disease.14 – 17 Because the motion velocity of the ventricular wall generally is much lower than the blood flow velocity in the ventricular cavity throughout the cardiac cycle, it also has a low frequency shift. Moreover, because the amplitude of Doppler signals derived from the myocardial tissue is about 40 dB larger than that derived from the blood flow, the wall motion velocity alone can be displayed by bypassing high-pass filter that eliminates low Doppler shifts. In this study, we used pulsed Doppler tissue imaging to measure the motion velocity at the endocardial portions of the LV wall, which is significantly greater than the velocity at the epicardial portions. Consequently, LV relaxation abnormalities associ-
METHODS/DOPPLER TISSUE IMAGING TO ASSESS LV RELAXATION
/ 2w1e 0887 Mp
927
Friday Mar 14 12:48 PM
EL–AJC (v. 79, no. 7 ’97)
0887
927
ated with various heart diseases can be evaluated accurately using the parameters derived from the posterior wall motion velocity as measured by pulsed Doppler tissue imaging. These analyses can be performed even in patients with pseudonormalization of transmitral flow velocity or with elevated LV enddiastolic pressure. Thus, this method provides important information that cannot be obtained by measuring isovolumic relaxation times or determining the parameters of the early diastolic wave of the transmitral flow velocity. Study limitations: Despite the advantages of evaluating LV diastolic function by Doppler tissue imaging, our analyses still have some limitations. First, we measured the motion velocity only at the endocardial portions of the LV wall and therefore could not calculate the transmyocardial velocity gradient. Consequently, disease-associated influences on the motion of the whole heart cannot be ruled out.27 However, the motion velocity at the endocardial portion generally is significantly higher than that at the epicardial portion. Furthermore, the goal of our study was not to obtain absolute values of the various parameters in patients with different conditions, but to determine differences between the patient groups and the control group and to assess the relationships between parameters derived from pulsed Doppler tissue imaging and the time constant. Therefore, the determination of the motion velocity only at the endocardial portions in this study has no clinical impact. Second, compared with the posterior wall, the wall motion velocity of the ventricular septum is likely to be more strongly affected by motions of the whole heart and hemodynamic changes of the right ventricle. In fact, the parameters obtained from our measurements at the ventricular septum did not correlate as well with the time constant as did those obtained from the posterior wall. Accordingly, it is not possible in pulsed Doppler tissue imaging studies to extrapolate important information on abnormal motion velocities of the LV wall by measuring the motion velocity only at the endocardial portion of the ventricular septum. Third, in patients with regional asynergy caused by anterior myocardial infarction or with hypertrophy of the LV wall due to asymmetric septal hypertrophic cardiomyopathy, the evaluation of global LV diastolic abnormalities solely from the motion velocity of the posterior wall will provide insufficient information. Final, Doppler tissue imaging has intrinsic technical limitations. As in echocardiographic examination, it cannot accurately reflect wall motion velocity if the direction of the beam is parallel to the wall motion (e.g., for the upper medial and upper lateral walls).
1. Grossman W, McLaurin LP. Diastolic properties of the left ventricle. Ann
Intern Med 1976;84:316–326.
928
THE AMERICAN JOURNAL OF CARDIOLOGYT
/ 2w1e 0887 Mp
928
VOL. 79
Friday Mar 14 12:48 PM
2. Bonow RO, Bacharach SL, Green MV, Kent KM, Rosing DR, Lipson LC, Leon MB, Epstein SE. Impaired left ventricular diastolic filling in patients with coronary artery disease: assessment with radionuclide angiography. Circulation 1981;64:315–323. 3. Dougherty AH, Naccarelli GV, Gray EL, Hicks CH, Goldstein RA. Congestive heart failure with normal systolic function. Am J Cardiol 1984;54:778– 782. 4. Ishida Y, Meisner JS, Tsujioka K, Gallo JI, Yoran C, Frater RWM, Yellin EL. Left ventricular filling dynamics: influence of left ventricular relaxation and left atrial pressure. Circulation 1986;74:187–196. 5. Weiss JL, Frederiksen JW, Weisfeldt ML. Hemodynamic determinants of the time-course of fall in canine left ventricular pressure. J Clin Invest 1976;58:751–761. 6. Upton MT, Gibson DG, Brown DJ. Echocardiographic assessment of abnormal left ventricular relaxation in man. Br Heart J 1978;38:1001–1009. 7. Hanrath P, Mathey DG, Siegert R, Bleifeld W. Left ventricular relaxation and filling pattern in different forms of left ventricular hypertrophy: an echocardiographic study. Am J Cardiol 1980;45:15–23. 8. Kitabatake A, Inoue M, Asao M, Tanouchi J, Masuyama T, Abe H, Morita H, Senda S, Matsuo H. Transmitral blood flow reflecting diastolic behaviour of the left ventricle in health and disease: a study by pulsed Doppler technique. Jpn Circ J 1982;46:92–102. 9. Appleton CP, Hatle LK, Popp RL. Demonstration of restrictive ventricular physiology by Doppler echocardiography. J Am Coll Cardiol 1988;11:757– 768. 10. Klein AL, Hatle LK, Burstow DJ, Seward JB, Kyle RA, Bailey KR, Luscher TF, Gertz MA, Tajik AJ. Doppler echocardiographic characterization of left ventricular diastolic dysfunction in cardiac amyloidosis. J Am Coll Cardiol 1989;13:1017–1026. 11. Oki T, Fukuda N, Iuchi A, Tabata T, Kiyoshige K, Manabe K, Kageji Y, Sasaki M, Hama M, Yamada H, Ito S. Evaluation of left ventricular diastolic hemodynamics from the left ventricular inflow and pulmonary venous flow velocities in hypertrophic cardiomyopathy. Jpn Heart J 1995;36:617–627. 12. Myreng Y, Smiseth OA. Assessment of left ventricular diastolic function by Doppler echocardiography: comparison of isovolumic relaxation time and transmitral flow velocities with time constant of isovolumic relaxation. Circulation 1990;81:260–266. 13. Thomas JD, Flachskampf FA, Chen C, Guererro JL, Picard MH, Levine RA, Weyman AE. Isovolumic relaxation time varies predictably with its time constant and aortic and left atrial pressures: implications for the noninvasive evaluation of ventricular relaxation. Am Heart J 1992;124:1305–1313. 14. McDicken WN, Sutherland GR, Gordon LN. Color Doppler velocity imaging of the myocardium. Ultrasound Med Biol 1992;18:651–654. 15. Yamazaki N, Mine Y, Sano A, Hirama M, Miyatake K, Yamagishi M, Tanaka N. Analysis of ventricular wall motion using color-coded tissue Doppler imaging system. Jpn J Appl Phys 1994;33:3141–3146. 16. Miyatake K, Yamagishi M, Tanaka N, Uematsu M, Yamazaki N, Mine Y, Sano A, Hirama M. New method for evaluating left ventricular wall motion by color-coded tissue Doppler imaging: in vitro and in vivo studies. J Am Coll Cardiol 1995;25:717–724. 17. Donovan CL, Armstrong WF, Bach DS. Quantitative Doppler tissue imaging of the left ventricular myocardium: validation in normal subjects. Am Heart J 1995;130:100–104. 18. Burch GE, Giles TD, Colcolough HL. Ischemic cardiomyopathy. Am Heart J 1970;79:291–292. 19. Sellers RD, Levy MJ, Amplatz K, Lillehei CW. Left retrograde cardioangiography in acquired cardiac disease. Am J Cardiol 1964;14:437–447. 20. Miyatake K, Okamoto M, Kinoshita N, Owa M, Nakasone I, Sakakibara H, Nimura Y. Augmentation of atrial contribution to left ventricular inflow with aging as assessed by intracardiac Doppler flowmetry. Am J Cardiol 1984;53:586–589. 21. Kuo LC, Quinones MA, Rokey R, Sartori M, Abinader EG, Zoghbi WA. Quantification of atrial contribution to left ventricular filling by pulsed Doppler echocardiography and the effect of age in normal and diseased hearts. Am J Cardiol 1987;59:1174–1178. 22. Lewis BS, Lewis N, Sapoznikov D, Gotsman MS. Isovolumic relaxation period in man. Am Heart J 1980;100:490–499. 23. Alvares RF, Shaver JA, Gamble WH, Goodwin JF. Isovolumic relaxation period in hypertrophic cardiomyopathy. J Am Coll Cardiol 1984;3:71–81. 24. Nishimura RA, Tajik AJ. Determination of left-sided pressure gradients by utilizing Doppler aortic and mitral regurgitant signals: validation by simultaneous dual catheter studies. J Am Coll Cardiol 1988;11:317–321. 25. Chen C, Rodriguez L, Levine RA, Weyman AE, Thomas JD. Noninvasive measurement of the time constant of left ventricular relaxation using the continuous-wave Doppler velocity profile of mitral regurgitation. Circulation 1992;86:272–278. 26. Nishimura RA, Schwartz RS, Tajik AJ, Holmes DR Jr. Noninvasive measurement of rate of left ventricular relaxation by Doppler echocardiography: validation with simultaneous cardiac catheterization. Circulation 1993;88:146– 155. 27. Uematsu M, Miyatake K, Tanaka N, Matsuda H, Sano A, Yamazaki N, Hirama M, Yamagishi M. Myocardial velocity gradient as a new indicator of regional left ventricular contraction: detection by a two-dimensional tissue Doppler imaging technique. J Am Coll Cardiol 1995;26:217–223.
APRIL 1, 1997
EL–AJC (v. 79, no. 7 ’97)
0887
MD,
Conventional assessment of left ventricular (LV) relaxation by calculating the time constant of LV pressure decay during the isovolumic diastole requires an invasive approach. Conversely, noninvasive parameters obtained by measuring isovolumic relaxation time and transmitral flow velocity often give inaccurate information. Using LV pressure curve, pulsed Doppler echocardiography, and pulsed Doppler tissue imaging in 38 patients with heart disease and 12 control subjects, we calculated the time constant and recorded transmitral flow velocity and motion velocities at the endocardial portions of the ventricular septum and LV posterior wall. Compared with the controls, patients exhibited a prolonged time constant, a decreased peak early diastolic velocity of the LV posterior wall, and a prolonged time interval from the second heart sound to the peak of the
early diastolic wave. The time constant correlated well with the isovolumic relaxation time and various parameters calculated from the transmitral flow velocity, except in patients with elevated LV end-diastolic pressure. In all subjects, the time constant correlated negatively with the peak early diastolic velocity of the posterior wall and positively with the time from the second heart sound to the peak of the early diastolic wave. Thus, early diastolic parameters derived from the motion velocity of the LV posterior wall by pulsed Doppler tissue imaging were closely related to the time constant. This technique may allow noninvasive evaluation of abnormal LV relaxation in patients with various heart diseases. Q1997 by Excerpta Medica, Inc. (Am J Cardiol 1997;79:921–928)
eft ventricular (LV) diastolic dysfunction usually precedes systolic dysfunction, L and abnormal relaxation is observed at its earliest stage. Con-
by pulsed Doppler tissue imaging for accurate evaluation of abnormal LV relaxation in patients with various heart diseases.
1–3
2–4
ventional clinical evaluation of LV relaxation involves determining the time constant of pressure decay during isovolumic diastole as calculated from the LV pressure curve.5 However, an invasive procedure is required to determine this parameter. There have been numerous attempts to use noninvasive methods to assess abnormal LV relaxation.6 – 8 These efforts have been hampered by the fact that abnormal LV relaxation often is masked in patients with strongly elevated left atrial pressure.9 – 11 Thus, it can be difficult to determine accurately the ventricular relaxation in patients with various hemodynamic backgrounds.4,12,13 Recently, a Doppler tissue imaging method has been developed in which large Doppler signals obtained from the ventricular wall can be selectively displayed as a color or pulsed Doppler image by eliminating small Doppler signals produced by the blood flow. This new technique is expected to produce valuable information on LV motion abnormalities in patients with heart disease.14 – 17 This study examines the usefulness of parameters obtained from the LV wall motion velocity as measured From the Second Department of Internal Medicine, Tokushima University School of Medicine, Tokushima, Japan and the Institute for Clinical Research, Zentsuji National Hospital, Zentsuji, Kagawa, Japan. Manuscript received August 5, 1996; revised manuscript received and accepted November 5, 1996. Address for reprints: Takashi Oki, MD, The Second Department of Internal Medicine, Tokushima University School of Medicine, 2-50 Kuramoto-cho, Tokushima 770, Japan.
METHODS Study population: We performed routine echocardiography, left cardiac catheterization, and coronary angiography in 100 consecutive Japanese patients with suspected cardiovascular disease based on clinical symptoms such as chest pain and dyspnea, abnormal findings in the electrocardiogram, cardiomegaly in the chest radiograph, and heart murmurs during auscultation. In 50 (32 men and 18 women, age range 39 to 72 years, mean 54 { 9) of the 100 patients, LV pressure curves were recorded using a high-fidelity manometer-tipped catheter. Pulsed Doppler echocardiography and Doppler tissue imaging were performed immediately before or simultaneously during cardiac catheterization. The examined subjects included those with ischemic heart disease (20 patients), hypertensive heart disease (8 patients), dilated cardiomyopathy (7 patients), cardiac amyloidosis (3 patients), and, as controls, 12 with the chest pain syndrome. The latter 12 subjects showed no significant cardiovascular disease by routine echocardiography and cardiac catheterization, including coronary angiography. Of the 20 patients with ischemic heart disease, 9 experienced no chest pain and, at rest, exhibited neither regional asynergy of the LV wall nor LV systolic dysfunction, although significant stenosis of 75% or more was observed in at least 1 branch of the coronary arteries, excluding the left anterior de-
Q1997 by Excerpta Medica, Inc.
0002-9149/97/$17.00 PII S0002-9149(97)00015-5
All rights reserved.
/ 2w1e 0887 Mp
921
Friday Mar 14 12:48 PM
EL–AJC (v. 79, no. 7 ’97)
0887
921
tion, however, was performed at a time when creatinine kinase values had returned to normal and LV asynergy was detected only between the anterior wall and the ventricular septum (systolic amplitudes of the LV wall motion measured from M-mode echogram; ventricular septum 0.1 { 2.6 mm, posterior wall 13.4 { 2.5 mm). The remaining 3 patients had lesions in the 3 branches of the coronary artery, diffuse asynergy of the LV wall, and signs of ischemic cardiomyFIGURE 1. Simultaneous recordings of the left ventricular pressure (LVP) curve and motion opathy (ß25% fractional shortening of the LV by M-mode velocity patterns of the ventricular septum (IVS; left ) and posterior wall (PW; right ) measured by pulsed Doppler tissue imaging. dP/dt Å first derivative of LV pressure curve; Ew echocardiography).18 Å peak early diastolic velocity of the LV wall; IIA-Ew Å time from the aortic component of All 8 patients with hypertenthe second heart sound to the peak of the early diastolic wave of the LV wall; ECG Å sive heart disease had a history of electrocardiogram; PCG Å phonocardiogram. hypertension for ú5 years, and their blood pressure was controlled by recent medical treatment. None of these patients showed abnormal LV wall motion, although 4 patients had symmetric hypertrophy of the LV wall of ¢12 mm as determined by M-mode echocardiography. The 7 patients with dilated cardiomyopathy showed no signs of significant stenosis or obstruction of the coronary artery; however, LV dilation (enddiastolic dimension by M-mode echocardiography ®6.0 cm) and diffuse asynergy of the LV wall (ß25% fractional shortening) were observed. All 3 patients with cardiac amyloidosis were positive for amyloid in the myocardial or rectal tissue, as determined by Congo-red staining. M-mode echocardiography detected symmetric hypertrophy of the LV wall of ¢12 mm and LV systolic dysfunction (ß30% fractional shortening). Mitral regurgitation was detected in 8 patients with coronary artery disease, 4 patients with dilated cardiomyopathy, and 2 patients with cardiac amyFIGURE 2. Measurement of variables obtained from the early diloidosis. According to Seller et al’s19 classification astolic wave of the transmitral flow velocity by pulsed Doppler by left ventriculography, its severity was õ2/ in all echocardiography. A Å atrial systolic wave; AC Å acceleration of the early diastolic wave; AT Å acceleration time from the start patients. of the early diastolic flow to the peak of the early diastolic wave; The objective of the examinations was explained DC Å deceleration of the early diastolic wave; DT Å deceleration to, and informed consent was obtained from each time from the peak of the early diastolic wave to the end of the subject. early diastolic flow; E Å peak velocity of the early diastolic wave; IRT Å time from the aortic component of the second heart Study protocol: CARDIAC CATHETERIZATION: In all sound (IIA) to the start of the early diastolic flow; other abbreviapatients, the LV pressure curve, its first derivative tions as in Figure 1. (dP/dt), the phonocardiogram, and the electrocardiogram were simultaneously recorded on paper at 50 scending branch. Another 3 patients had effort an- or 100 mm/s using a standard percutaneous femoral gina with significant stenosis of 75% or more in at approach and a 7F high-fidelity manometer-tipped least 1 of the coronary artery branches, excluding the catheter (Figure 1). Although the time constant of left anterior descending branch. These patients were LV pressure decay during isovolumic diastole has examined in the absence of an attack when asynergy largely been calculated assuming a zero asymptote of the LV wall and LV systolic dysfunction were by means of nonlinear least-squares parameter estiabsent. In 5 patients, complete obstruction of seg- mation,13 we used the method of Weiss et al5 in this ment 6 or 7 of the left anterior descending coronary study. The LV end-diastolic pressure also was meaartery had been observed during emergency coro- sured just before coronary angiography and left vennary angiography at the acute phase. Our examina- triculography. 922
THE AMERICAN JOURNAL OF CARDIOLOGYT
/ 2w1e 0887 Mp
922
VOL. 79
Friday Mar 14 12:48 PM
APRIL 1, 1997
EL–AJC (v. 79, no. 7 ’97)
0887
umes were set at the endocardial portions of the basilar, middle, and apical sites of both LV walls (i.e., ventricular septum and posterior wall). The motion velocity patterns at each site were recorded by the pulsed Doppler method using a Toshiba SSA-380A instrument (Figure 3). From the obtained patterns, the peak early diastolic velocities and the times from the aortic component of the second heart sound to the peak of the early diastolic wave of both the LV walls were determined (Figure 1). Statistical analysis: Values are expressed as means { SD. Mean values in different patient groups and at each site of the ventricular septum and posterior wall were compared by analyses of variance and covariance, respectively, and the unpaired Scheffe’s test. Linear regression coefficients were obtained to show the degree of correlation among variables. A p level õ0.05 was considered statistically significant.
RESULTS FIGURE 3. Sample recording of the motion velocity patterns of the ventricular septum (IVS) and posterior wall (PW) by pulsed Doppler tissue imaging in the parasternal long-axis view of the left ventricle. Sample volumes (white circles) were set at the endocardial portions of the basilar (B), middle (M), and apical (A) sites of the ventricular septum and posterior wall. Ao Å ascending aorta; LA Å left atrium; RV Å right ventricle; LV Å left ventricle. PULSED DOPPLER ECHOCARDIOGRAPHY: A sample volume was set at the mitral valve orifice in the longaxis view of the left ventricle or the 4-chamber view recorded from the cardiac apex, and transmitral flow velocity patterns were recorded using a commercially available Toshiba SSA-380A (Toshiba Corporation, Tokyo, Japan; 3.75-MHz probe). From the obtained early diastolic wave, the peak velocity, acceleration, acceleration time from the start of the early diastolic flow to the peak of the early diastolic wave, deceleration, and deceleration time from the peak of the early diastolic wave to the end of the early diastolic flow were determined (Figure 2). The isovolumic relaxation time was determined as the time from the aortic component of the second heart sound to the start of the early diastolic flow. DOPPLER TISSUE IMAGING: In the parasternal longaxis echocardiogram of the left ventricle, sample vol-
Clinical data: The group of patients with heart disease and the control group did not differ significantly as to age or heart rate (Table I). The 38 patients were classified into 2 groups with respect to transmitral flow velocity patterns. Nine patients (5 with dilated cardiomyopathy, 2 with ischemic cardiomyopathy, and 2 with cardiac amyloidosis) exhibited a pseudonormalized pattern; that is, the ratio of the peak velocity of the atrial systolic wave to the peak velocity of the early diastolic wave (A/E) was õ1. The remaining 29 patients demonstrated a decrease in the peak early diastolic velocity and a compensatory increase in the peak atrial systolic velocity (A/E ®1). This group included 5 patients with anterior myocardial infarction. The 9 patients with a pseudonormalized transmitral flow velocity had a significantly lower systolic blood pressure than the other patients and the control group. Time constant and left ventricular end-diastolic pressure: The time constant of LV pressure decay during
an isovolumic diastole was significantly or slightly prolonged in the 3 patient groups compared with the control group (Table I). The increase in the time constant was greatest in the A/E õ1 group. The LV enddiastolic pressure in the patients with A/E õ1 was significantly higher than in the controls or in the A/E ®1 group. In patients with anterior myocardial
TABLE I Clinical Data and Hemodynamic Variables Group Control Patients A/E ¢1 A/E õ1 Anterior MI
No. of Cases
Age (yr)
Heart Rate (beats/min)
SBP (mm Hg)
DBP (mm Hg)
Tau (ms)
12
56 { 17
72 { 10
128 { 20
70 { 15
39 { 2
24 9 5
62 { 10 58 { 8 60 { 4
70 { 8 74 { 11 69 { 7
130 { 14 110 { 18*,§ 121 { 13
83 { 9† 62 { 6x 73 { 10x,Ø
50 { 9† 63 { 6‡,§ 50 { 4#
LVEDP (mm Hg) 9{4 12 { 7 19 { 5‡,§ 14 { 5*
*p õ0.05 vs control group; †p õ0.01 vs control group; ‡p õ0.001 vs control group; §p õ0.01 vs A/E ¢1 group; xp õ0.001 vs A/E ¢1 group; Øp õ0.05 vs A/E õ1 group; #p õ0.001 vs A/E õ1 group. A/E Å peak velocity ratio of the atrial systolic to the early diastolic wave in the transmitral flow; DBP Å diastolic blood pressure; LVEDP Å left ventricular enddiastolic pressure; MI Å myocardial infarction; SBP Å systolic blood pressure; Tau Å time constant calculated from the left ventricular pressure decay at isovolumic diastole.
METHODS/DOPPLER TISSUE IMAGING TO ASSESS LV RELAXATION
/ 2w1e 0887 Mp
923
Friday Mar 14 12:48 PM
EL–AJC (v. 79, no. 7 ’97)
0887
923
TABLE II Variables Derived from Transmitral Flow Velocity IRT (ms)
Group Control (n Å 12) Patients (n Å 38) A/E ¢1 (n Å 24) A/E õ1 (n Å 9) Anterior MI (n Å 5)
E-AC (mm/s2)
E-AT (ms)
75 { 6
751 { 70
87 { 10
87 { 18* 69 { 7‡ 86 { 11*,Ø
515 { 175† 772 { 122§ 520 { 37*,**
111 { 22† 89 { 11‡ 106 { 12Ø
E-DC (mm/s2)
E-DT (ms)
E (cm/s)
485 { 139
169 { 50
69.9 { 8.6
357 { 206 771 { 139†,x 361 { 85††
206 { 60 103 { 24*,x 162 { 31#
53.4 { 12.7† 83.5 { 22.4x 55.8 { 9.8Ø
*p õ0.05 vs control group; †p õ0.01 vs control group; ‡p õ0.05 vs A/E ¢1 group; §p õ0.01 vs A/E ¢1 group; xp õ0.001 vs A/E ¢1 group; Øp õ0.05 vs A/E õ1 group; #p õ0.01 vs A/E õ1 group; **p õ0.001 vs A/E õ1 group; ††p õ0.0001 vs A/E õ1 group. A/E Å peak velocity ratio of the atrial systolic to the early diastolic wave in the transmitral flow; E Å peak velocity of the early diastolic wave; E-AC Å acceleration of the early diastolic wave; E-AT Å acceleration time from the start of the early diastolic flow to the peak of the early diastolic wave; E-DC Å deceleration of the early diastolic wave; E-DT Å deceleration time from the peak of the early diastolic wave to the end of the early diastolic flow; IRT Å time from the aortic component of the second heart sound (IIA) to the start of the early diastolic flow; MI Å myocardial infarction.
FIGURE 4. Correlations between the time constant (Tau) and the isovolumic relaxation time and variables of the early diastolic wave of transmitral flow velocity. A/E Å peak velocity ratio of the atrial systolic to the early diastolic wave in the transmitral flow; E Å peak velocity of the early diastolic wave; E-AC Å acceleration of the early diastolic wave; E-AT Å acceleration time from the start of the early diastolic flow to the peak of the early diastolic wave; E-DC Å deceleration of the early diastolic wave; E-DT Å deceleration time from the peak of the early diastolic wave to the end of the early diastolic flow; MI Å myocardial infarction; other abbreviations as in Figure 2.
infarction, the LV end-diastolic pressure tended to be elevated compared with the control group but did not differ significantly from the A/E ®1 group. Transmitral flow velocity: Determination of the transmitral flow velocity in the 4 experimental groups allowed calculation of several relevant variables. The isovolumic relaxation times in the patients with A/E ®1 or with anterior myocardial infarction were increased significantly compared with the control group (Table II). In contrast, patients with A/E 924
THE AMERICAN JOURNAL OF CARDIOLOGYT
/ 2w1e 0887 Mp
924
VOL. 79
Friday Mar 14 12:48 PM
õ1 had a significantly shorter isovolumic relaxation time than the A/E ®1 group, but did not differ significantly from the control group. The A/E ®1 group had a significantly prolonged acceleration time of the early diastolic wave and a significantly decreased acceleration and peak velocity of the early diastolic wave compared with the control group. The A/E õ1 group, in contrast, was characterized by significant decreases in the acceleration time and deceleration time of the early diaAPRIL 1, 1997
EL–AJC (v. 79, no. 7 ’97)
0887
Ew (cm/s)
129 { 14
IIA-Ew (ms)
3.4 { 1.2
4.8 { 1.5
4.3 { 1.2
Ew (cm/s)
179 { 18*
162 { 21
171 { 30†
16.4 { 1.0§,#
5.4 { 1.2‡,§
TABLE III Variables Derived from Pulsed Doppler Tissue Imaging
6.6 { 1.2
165 { 39*
3.4 { 1.8
160 { 11‡
138 { 30*
14.7 { 0.9Ø,#
5.0 { 0.7‡,x
8.0 { 2.8‡
120 { 5§,#
159 { 12†
139 { 36
Ew (cm/s) IIA-Ew (ms)
111 { 6
Ew (cm/s)
13.8 { 1.2
IIA-Ew (ms)
114 { 5
PW (apical)
9.7 { 3.2‡
102 { 7§,#
PW (middle)
Ew (cm/s)
112 { 5
4.9 { 1.0‡,Ø
IIA-Ew (ms)
IIA-Ew (ms)
15.0 { 1.4
133 { 30
15.8 { 0.9Ø,#
14.7 { 1.4
133 { 14
10.9 { 3.8*
159 { 12†,§
105 { 6#
PW (basilar)
IIA-Ew (ms)
5.5 { 1.4
175 { 18*
158 { 19
IVS (apical)
128 { 15
3.8 { 1.0†,§
IVS (middle)
155 { 38
3.8 { 1.7*
IVS (basilar)
6.8 { 1.3
166 { 14*
Ew (cm/s)
6.1 { 2.7
174 { 18*
Group
A/E ®1 (n Å 24)
4.0 { 2.0
3.7 { 0.8*,§
Control (n Å 12)
A/E õ1 (n Å 9)
Patients (n Å 38)
Anterior MI (n Å 5)
*p õ0.05 vs control group; †p õ0.01 vs control group; ‡p õ0.001 vs control group; §p õ0.05 vs A/E ®1 group; xp õ0.01 vs A/E ®1 group; Øp õ0.001 vs A/E ®1 group; #p õ0.0001 vs A/E õ1 group.
A/E Å peak velocity ratio of the atrial systolic to the early diastolic wave in the transmitral flow; Ew Å peak early diastolic velocity of the left ventricular wall; IVS Å interventricular septum; MI Å myocardial infarction; PW Å left ventricular
posterior wall; IIA-Ew Å time from the aortic component of the second heart sound to the peak of the early diastolic wave of the left ventricular wall.
stolic wave, as well as by significant increases in acceleration, deceleration, and peak velocity of the early diastolic wave compared with the A/E ®1 group. There were no significant differences in isovolumic relaxation time, acceleration, acceleration time, and peak velocity of the early diastolic wave between the A/E õ1 and control groups. In all subjects, the time constant was weakly correlated with isovolumic relaxation time (r Å 0.32, p õ0.05), acceleration of the early diastolic wave (r Å 00.32, p õ0.05), and acceleration time of the early diastolic wave (r Å 0.36, p õ0.05) (Figure 4). When the 9 patients of the A/E õ1 group were excluded from this analysis, a strong correlation existed between the time constant and the isovolumic relaxation time (r Å 0.77, p õ0.0001), acceleration of the early diastolic wave (r Å 00.83, p õ0.0001), and acceleration time of the early diastolic wave (r Å 0.88, p õ0.0001). No significant correlations existed between the time constant and the deceleration, deceleration time, and peak velocity of the early diastolic wave. Left ventricular wall motion velocity: Pulsed Doppler tissue imaging demonstrated that in all subjects the peak early diastolic velocities of the ventricular septum and posterior wall decreased gradually between the basilar and apical sites, whereas the time from the second heart sound to the peak of the early diastolic wave increased gradually (Table III). Moreover, the peak early diastolic velocity at each site of the ventricular septum was significantly lower than at the corresponding sites of the posterior wall (p õ0.01, p õ0.001, or p õ0.0001 for the basilar, middle, and apical sites) except for the A/E õ1 group. In contrast, the time from the second heart sound to the peak of the early diastolic wave was significantly longer at the ventricular septum than at the posterior wall in all experimental groups (p õ0.01, p õ0.001, or p õ0.0001 for the basilar, middle, and apical sites) except for the A/E õ1 group. Furthermore, in the patients with A/E õ1, the peak early diastolic velocity at the basilar and middle portions of the ventricular septum was significantly lower than in the control and A/E ®1 groups. In the patients with anterior myocardial infarction, the peak early diastolic velocity at the middle site of the ventricular septum was significantly reduced compared with the control group. At the posterior wall, peak early diastolic velocities at all 3 sites were significantly lower in the A/E ®1 and A/E õ1 groups than in the control group, whereas the time from the second heart sound to the peak of the early diastolic wave was significantly or slightly prolonged. In the anterior myocardial infarction group, the peak early diastolic velocity was significantly greater and the time from the second heart sound to the peak of the early diastolic wave was significantly or slightly decreased at the basilar to apical sites of the posterior wall compared with the A/E ®1 and A/E õ1 groups.
METHODS/DOPPLER TISSUE IMAGING TO ASSESS LV RELAXATION
/ 2w1e 0887 Mp
925
Friday Mar 14 12:48 PM
EL–AJC (v. 79, no. 7 ’97)
0887
925
FIGURE 5. Correlations between the time constant (Tau) and the peak early diastolic velocity and time from the aortic component of the second heart sound to the peak of the early diastolic wave measured by pulsed Doppler tissue imaging method at each site of the ventricular septum. IVS-B-Ew; IVS-M-Ew, and IVS-A-Ew Å peak early diastolic velocity at the basilar, middle, and apical sites of the ventricular septum, respectively; IVS-B-(IIA-Ew), IVS-M-(IIA-Ew), and IVS-A-(IIA-Ew) Å time from the aortic component of the second heart sound to the peak of the early diastolic wave at the basilar, middle, and apical sites of the ventricular septum, respectively; MI Å myocardial infarction; other abbreviations as in Figures 2 to 4.
The time constants in all 50 subjects were negatively correlated with the peak early diastolic velocities at the basilar and middle sites of the ventricular septum (r Å 00.34, p õ0.05; r Å 00.46, p õ0.01, respectively) (Figure 5, top), and positively correlated with the time from the second heart sound to the peak of the early diastolic wave at the middle and apical sites of the ventricular septum (r Å 0.29, p õ0.05; r Å 0.47, p õ0.001, respectively) (Figure 5, bottom). However, no significant correlations between these parameters existed at the other sites of the ventricular septum. At all sites of the posterior wall, on the other hand, the time constant was strongly and negatively correlated with the peak early diastolic velocity (basilar: r Å 00.81, p õ0.0001; middle: r Å 00.78, p õ0.0001; apical: r Å 00.69, p õ0.0001) (Figure 6, top), and strongly and positively correlated with the time from the second heart sound to the peak of the early diastolic wave (basilar: r Å 0.80, p õ0.0001; middle: r Å 0.81, p õ0.0001; apical: r Å 0.71, p õ0.0001) (Figure 6, bottom). In this analysis, the 5 patients with anterior myocardial infarction were unique in that they had a higherthan-average peak early diastolic velocity and a shorter-than-average time from the second heart 926
THE AMERICAN JOURNAL OF CARDIOLOGYT
/ 2w1e 0887 Mp
926
VOL. 79
Friday Mar 14 12:48 PM
sound to the peak of the early diastolic wave at all 3 sites of the posterior wall.
DISCUSSION To evaluate the diastolic function of the LV accurately, it is necessary to assess LV relaxation at the isovolumic diastole as well as LV filling, which, in turn, is determined by the relationship between LV volume and pressure after opening of the mitral valve.1 LV relaxation abnormalities sometimes appear before the occurrence of LV systolic dysfunction.1 – 3 Moreover, these abnormalities have been reported to develop with age even in healthy subjects.20,21 The time constant calculated from the pressure decay during early diastole in the LV pressure curve is well known as a parameter assessing LV relaxation abnormalities.5 This method is rarely used, however, because it requires invasive measurements. More recently, several studies have used the increasingly popular pulsed and continuous wave Doppler echocardiographic approach to detect LV relaxation abnormalities noninvasively. For instance, isovolumic relaxation time can be determined by measuring the time from the aortic component of the second heart sound to the opening of the mitral APRIL 1, 1997
EL–AJC (v. 79, no. 7 ’97)
0887
FIGURE 6. Correlations between the time constant (Tau) and the peak early diastolic velocity and time from the aortic component of the second heart sound to the peak of the early diastolic wave measured by pulsed Doppler tissue imaging method at each site of the posterior wall. PW-B-Ew, PW-M-Ew, and PW-A-Ew Å peak early diastolic velocity at the basilar, middle, and apical sites of the posterior wall, respectively; PW-B-(IIA-Ew), PW-M-(IIA-Ew), and PW-A-(IIA-Ew) Å time from the aortic component of the second heart sound to the peak of the early diastolic wave at the basilar, middle, and apical sites of the posterior wall, respectively; MI Å myocardial infarction.
valve.6,7,22,23 Many other parameters—such as peak velocity, acceleration, deceleration, acceleration time, and deceleration time of the early diastolic wave—can be determined from the transmitral flow velocity.8,11 However, these parameters are influenced strongly by aortic or left atrial pressure.4,12,13 In patients with significantly elevated left atrial pressure or with restrictive physiology, the transmitral flow velocity shows pseudonormalization.9 – 11 In these cases, the isovolumic relaxation time and the parameters obtained from the early diastolic wave frequently appear almost normal, despite an increase in the time constant. These observations, as well as our results in this study, indicate that the parameters of the early diastolic wave or isovolumic relaxation time correlate with the time constant only under a certain level of preload increase. Beyond this level, these parameters cannot be used to evaluate LV relaxation abnormalities. Other studies have attempted to evaluate LV relaxation abnormalities associated with various heart diseases using early diastolic envelopes of the mitral and aortic regurgitant velocity patterns obtained from continuous wave Doppler echocardiography.24–26 The relaxation parameters obtained by this method correlated closely with the time constant calculated
from the LV pressure curve, indicating that it can aid in noninvasively evaluating LV relaxation abnormalities. However, this method is applicable only to patients with complications from mitral or aortic regurgitation and requires a complete and clear recording of the envelopes of the regurgitant velocity patterns. A method of Doppler tissue imaging has been developed to measure the motion velocity in myocardial tissue. This method has been used to evaluate the ventricular wall motion velocity quantitatively in patients with various kinds of heart disease.14 – 17 Because the motion velocity of the ventricular wall generally is much lower than the blood flow velocity in the ventricular cavity throughout the cardiac cycle, it also has a low frequency shift. Moreover, because the amplitude of Doppler signals derived from the myocardial tissue is about 40 dB larger than that derived from the blood flow, the wall motion velocity alone can be displayed by bypassing high-pass filter that eliminates low Doppler shifts. In this study, we used pulsed Doppler tissue imaging to measure the motion velocity at the endocardial portions of the LV wall, which is significantly greater than the velocity at the epicardial portions. Consequently, LV relaxation abnormalities associ-
METHODS/DOPPLER TISSUE IMAGING TO ASSESS LV RELAXATION
/ 2w1e 0887 Mp
927
Friday Mar 14 12:48 PM
EL–AJC (v. 79, no. 7 ’97)
0887
927
ated with various heart diseases can be evaluated accurately using the parameters derived from the posterior wall motion velocity as measured by pulsed Doppler tissue imaging. These analyses can be performed even in patients with pseudonormalization of transmitral flow velocity or with elevated LV enddiastolic pressure. Thus, this method provides important information that cannot be obtained by measuring isovolumic relaxation times or determining the parameters of the early diastolic wave of the transmitral flow velocity. Study limitations: Despite the advantages of evaluating LV diastolic function by Doppler tissue imaging, our analyses still have some limitations. First, we measured the motion velocity only at the endocardial portions of the LV wall and therefore could not calculate the transmyocardial velocity gradient. Consequently, disease-associated influences on the motion of the whole heart cannot be ruled out.27 However, the motion velocity at the endocardial portion generally is significantly higher than that at the epicardial portion. Furthermore, the goal of our study was not to obtain absolute values of the various parameters in patients with different conditions, but to determine differences between the patient groups and the control group and to assess the relationships between parameters derived from pulsed Doppler tissue imaging and the time constant. Therefore, the determination of the motion velocity only at the endocardial portions in this study has no clinical impact. Second, compared with the posterior wall, the wall motion velocity of the ventricular septum is likely to be more strongly affected by motions of the whole heart and hemodynamic changes of the right ventricle. In fact, the parameters obtained from our measurements at the ventricular septum did not correlate as well with the time constant as did those obtained from the posterior wall. Accordingly, it is not possible in pulsed Doppler tissue imaging studies to extrapolate important information on abnormal motion velocities of the LV wall by measuring the motion velocity only at the endocardial portion of the ventricular septum. Third, in patients with regional asynergy caused by anterior myocardial infarction or with hypertrophy of the LV wall due to asymmetric septal hypertrophic cardiomyopathy, the evaluation of global LV diastolic abnormalities solely from the motion velocity of the posterior wall will provide insufficient information. Final, Doppler tissue imaging has intrinsic technical limitations. As in echocardiographic examination, it cannot accurately reflect wall motion velocity if the direction of the beam is parallel to the wall motion (e.g., for the upper medial and upper lateral walls).
1. Grossman W, McLaurin LP. Diastolic properties of the left ventricle. Ann
Intern Med 1976;84:316–326.
928
THE AMERICAN JOURNAL OF CARDIOLOGYT
/ 2w1e 0887 Mp
928
VOL. 79
Friday Mar 14 12:48 PM
2. Bonow RO, Bacharach SL, Green MV, Kent KM, Rosing DR, Lipson LC, Leon MB, Epstein SE. Impaired left ventricular diastolic filling in patients with coronary artery disease: assessment with radionuclide angiography. Circulation 1981;64:315–323. 3. Dougherty AH, Naccarelli GV, Gray EL, Hicks CH, Goldstein RA. Congestive heart failure with normal systolic function. Am J Cardiol 1984;54:778– 782. 4. Ishida Y, Meisner JS, Tsujioka K, Gallo JI, Yoran C, Frater RWM, Yellin EL. Left ventricular filling dynamics: influence of left ventricular relaxation and left atrial pressure. Circulation 1986;74:187–196. 5. Weiss JL, Frederiksen JW, Weisfeldt ML. Hemodynamic determinants of the time-course of fall in canine left ventricular pressure. J Clin Invest 1976;58:751–761. 6. Upton MT, Gibson DG, Brown DJ. Echocardiographic assessment of abnormal left ventricular relaxation in man. Br Heart J 1978;38:1001–1009. 7. Hanrath P, Mathey DG, Siegert R, Bleifeld W. Left ventricular relaxation and filling pattern in different forms of left ventricular hypertrophy: an echocardiographic study. Am J Cardiol 1980;45:15–23. 8. Kitabatake A, Inoue M, Asao M, Tanouchi J, Masuyama T, Abe H, Morita H, Senda S, Matsuo H. Transmitral blood flow reflecting diastolic behaviour of the left ventricle in health and disease: a study by pulsed Doppler technique. Jpn Circ J 1982;46:92–102. 9. Appleton CP, Hatle LK, Popp RL. Demonstration of restrictive ventricular physiology by Doppler echocardiography. J Am Coll Cardiol 1988;11:757– 768. 10. Klein AL, Hatle LK, Burstow DJ, Seward JB, Kyle RA, Bailey KR, Luscher TF, Gertz MA, Tajik AJ. Doppler echocardiographic characterization of left ventricular diastolic dysfunction in cardiac amyloidosis. J Am Coll Cardiol 1989;13:1017–1026. 11. Oki T, Fukuda N, Iuchi A, Tabata T, Kiyoshige K, Manabe K, Kageji Y, Sasaki M, Hama M, Yamada H, Ito S. Evaluation of left ventricular diastolic hemodynamics from the left ventricular inflow and pulmonary venous flow velocities in hypertrophic cardiomyopathy. Jpn Heart J 1995;36:617–627. 12. Myreng Y, Smiseth OA. Assessment of left ventricular diastolic function by Doppler echocardiography: comparison of isovolumic relaxation time and transmitral flow velocities with time constant of isovolumic relaxation. Circulation 1990;81:260–266. 13. Thomas JD, Flachskampf FA, Chen C, Guererro JL, Picard MH, Levine RA, Weyman AE. Isovolumic relaxation time varies predictably with its time constant and aortic and left atrial pressures: implications for the noninvasive evaluation of ventricular relaxation. Am Heart J 1992;124:1305–1313. 14. McDicken WN, Sutherland GR, Gordon LN. Color Doppler velocity imaging of the myocardium. Ultrasound Med Biol 1992;18:651–654. 15. Yamazaki N, Mine Y, Sano A, Hirama M, Miyatake K, Yamagishi M, Tanaka N. Analysis of ventricular wall motion using color-coded tissue Doppler imaging system. Jpn J Appl Phys 1994;33:3141–3146. 16. Miyatake K, Yamagishi M, Tanaka N, Uematsu M, Yamazaki N, Mine Y, Sano A, Hirama M. New method for evaluating left ventricular wall motion by color-coded tissue Doppler imaging: in vitro and in vivo studies. J Am Coll Cardiol 1995;25:717–724. 17. Donovan CL, Armstrong WF, Bach DS. Quantitative Doppler tissue imaging of the left ventricular myocardium: validation in normal subjects. Am Heart J 1995;130:100–104. 18. Burch GE, Giles TD, Colcolough HL. Ischemic cardiomyopathy. Am Heart J 1970;79:291–292. 19. Sellers RD, Levy MJ, Amplatz K, Lillehei CW. Left retrograde cardioangiography in acquired cardiac disease. Am J Cardiol 1964;14:437–447. 20. Miyatake K, Okamoto M, Kinoshita N, Owa M, Nakasone I, Sakakibara H, Nimura Y. Augmentation of atrial contribution to left ventricular inflow with aging as assessed by intracardiac Doppler flowmetry. Am J Cardiol 1984;53:586–589. 21. Kuo LC, Quinones MA, Rokey R, Sartori M, Abinader EG, Zoghbi WA. Quantification of atrial contribution to left ventricular filling by pulsed Doppler echocardiography and the effect of age in normal and diseased hearts. Am J Cardiol 1987;59:1174–1178. 22. Lewis BS, Lewis N, Sapoznikov D, Gotsman MS. Isovolumic relaxation period in man. Am Heart J 1980;100:490–499. 23. Alvares RF, Shaver JA, Gamble WH, Goodwin JF. Isovolumic relaxation period in hypertrophic cardiomyopathy. J Am Coll Cardiol 1984;3:71–81. 24. Nishimura RA, Tajik AJ. Determination of left-sided pressure gradients by utilizing Doppler aortic and mitral regurgitant signals: validation by simultaneous dual catheter studies. J Am Coll Cardiol 1988;11:317–321. 25. Chen C, Rodriguez L, Levine RA, Weyman AE, Thomas JD. Noninvasive measurement of the time constant of left ventricular relaxation using the continuous-wave Doppler velocity profile of mitral regurgitation. Circulation 1992;86:272–278. 26. Nishimura RA, Schwartz RS, Tajik AJ, Holmes DR Jr. Noninvasive measurement of rate of left ventricular relaxation by Doppler echocardiography: validation with simultaneous cardiac catheterization. Circulation 1993;88:146– 155. 27. Uematsu M, Miyatake K, Tanaka N, Matsuda H, Sano A, Yamazaki N, Hirama M, Yamagishi M. Myocardial velocity gradient as a new indicator of regional left ventricular contraction: detection by a two-dimensional tissue Doppler imaging technique. J Am Coll Cardiol 1995;26:217–223.
APRIL 1, 1997
EL–AJC (v. 79, no. 7 ’97)
0887