In humans, the use of TDI for the examination of LV diastolic function has been investigated.1-4 Early diastolic myocardial velocity is a well-known indicator of LV relaxation and is correlated with tau and the dP/dt values during Doppler-derived diastole.3,5 Whereas assessments of diastolic dysfunction via measurement of TMF are limited because of pseudonormalization, E′ velocity has been reported to be useful for assessment of LV diastolic dysfunction in symptomatic humans with a pseudonormal mitral inflow pattern.6 Further-more, as determined in dogs with experimental pacinginduced heart failure, TDI-derived myocardial systolic velocity correlates with the LV ejection fraction.7 Also, the TDI-derived MPI correlates well with systolic and diastolic function.1 Thus, TDI is believed to provide detailed information about LV systolic and diastolic function.8,9 In addition, myocardial velocity measurements obtained via longitudinal views differ from those obtained in short-axis views in dogs.9 However, it remains controversial whether longitudinal myocardial profiles derived from the VS or FW are more reliable in assessment of LV systolic function. Thus, the purpose of the study reported here was to evaluate TDI of the LV FW and LV VS as an indicator of LV systolic function in dogs. To this end, the reliability of longitudinal myocardial profiles derived from FW- and VS-TDI and the relationship between β-adrenergic receptor–modulated LV function and TDI-derived myocardial velocity profiles was investigated.
Materials and Methods
Animals—Seven healthy sexually intact male Beagles that were 1 to 2 years old and weighed 8 to 12 kg were used in this study. The dogs were housed individually in cages and fed commercial dry food with free access to water. The study followed the Guidelines for Institutional Laboratory Animal Care and Use of the School of Veterinary Medicine at Kitasato University, Japan.
Following sedation with butorphanol (0.2 mg/kg, IV) and atropine (0.025 mg/kg, SC), each dog was anesthetized with propofol (6.0 mg/kg, IV) and intubated. Anesthesia was maintained with 2.0% isoflurane in oxygen. The dog was positioned in left lateral recumbency. The respiratory rate was maintained with an artificial ventilator,a the end-tidal PaCO2 was monitored and maintained at 35 to 45 mm Hg, and heart rate was monitored via ECG.b Under fluoroscopic guidance, a high-fidelity 3.5-F micromanometer-tipped catheterc was placed through the right carotid artery into the LV. The LVPS and LVEDP were measured, and the peak positive and negative dP/dt (+dP/dt and –dP/dt, respectively) values were calculated. After completing the procedures, a 20- to 30-minute stabilization period was allowed to establish a stable baseline condition for the hemodynamic and echocardiographic measurements. Following the examinations, the dogs were allowed to recover from anesthesia.
Drug administration—Dobutamine was infused at a rate of 5 or 10 μg/kg/min for 5 minutes via a cephalic vein.4,5 Similarly, esmolol was infused at a rate of 50 or 100 μg/kg/min for 5 minutes via a cephalic vein.1 Each dog received each of the 4 drug doses. Five minutes after administration of each dose of dobutamine or esmolol, measurements were made. The order of drug administration (dobutamine or esmolol) was randomly assigned to each dog, and the interval between administrations of different drugs was at least 30 minutes. After completing the first procedure, a stabilization period of at least 30 minutes was provided to reestablish a stable baseline condition.
Echocardiography—Each dog was positioned in left lateral recumbency for echocardiographic examination. The PWD and TDI velocities were obtained from the apical long-axis view, and all echocardiographic measurements were made during the expiratory phase of respiration. Transthoracic echocardiography was performed by use of an ultrasonographic systemd with a 12-MHz probe. The echocardiographic images were analyzed by use of the commercial analysis software package supplied with the system. The data were stored digitally and analyzed off-line by a single observer (YH). To obtain the PWD and TDI velocities, the mean values of 3 cardiac cycles were calculated.
Pulsed-wave Doppler echocardiography was used to measure the TMF velocity with the sample volume positioned at the tip of the mitral valve leaflets. The E-wave and A-wave TMF velocities were measured, and the E:A ratio was then calculated. Aortic outflow PWD echocardiographic measurements were performed with the sample volume placed just below the aortic valve. The ET was measured from the onset to the end of the aortic outflow. Time interval measurements were made with the internal analysis package of the ultrasound unitd; the intervals were determined by use of 2 vertical cursors that were moved with a track ball. From the PWD recordings, the MPI was calculated by use of standard procedures; the total isovolumic time (IVRT plus IVCT) was divided by ET.10,11 The time from the cessation of the mitral valve A wave to the onset of the mitral valve E wave of the next cardiac cycle (a) is equal to the total isovolumic time plus the ET (b). The MPI was calculated as a minus ≤ divided by ≤ (Figure 1). The IVRT was calculated by subtraction of the interval between the peak of the R wave and the end of the ET from the interval between the peak of the R wave and the onset of the E wave. The IVCT was calculated by subtraction of the ET and IVRT from the interval between the cessation of the mitral valve A wave and the onset of the mitral valve E wave of the next cardiac cycle.
Representative echocardiographic TMF velocity and ET assessments (apical long-axis views) performed via PWD echocardiography (sample volume positioned at the tip of the mitral valve leaflets; A) and via TDI (sample volume positioned at the FW [B] and the VS [C] of the mitral valve annulus) in a healthy dog. Images were used to calculate the PWD- and TDI-derived MPI values. At the top of each view, the corresponding ECG trace is shown. Horizontal markers represent increments of 20 cm/s (PWD) and 5 cm/s (TDI).
Citation: American Journal of Veterinary Research 68, 10; 10.2460/ajvr.68.10.1051
The TDI program was set to PWD mode, and filters were set to exclude high-frequency signals. Gains were minimized to allow for a clear tissue signal with minimal background noise. A 2-mm sample volume was placed at the FW and VS of the mitral valve annulus. The peak myocardial velocity was measured during systole (S′), early diastole (E′), and late diastole (A′) (Figure 1). The ratio of the E′ wave to the A′ wave (E′: A′ ratio) and the ratio of the E wave to the E′ wave (E: E′ ratio) were calculated. From the TDI recordings, the duration of the S′ wave was measured from the onset to the end of the S′ wave. The IVCT was measured from the end of the A′ wave to the onset of the S′ wave. The IVRT was measured from the end of the S′ wave to the onset of the E′ wave. The modified MPI obtained via TDI was calculated as (IVCT plus IVRT) divided by S′ wave duration.1
Statistical analysis—The data are described as mean ± SD values. Changes in the hemodynamic and echocardiographic measurements were compared with the baseline value established for each different condition by use of a 1-factor repeated-measures ANOVA. Echocardiographic measurements from the PWD examination and the FW- and VS-derived TDI examinations (including IVRT, IVCT, ET, and MPI) were analyzed by use of a 1-way ANOVA. The significance of the differences between the mean values at baseline and each condition was tested by use of the post hoc Tukey multiple comparison test. A paired t test was used to compare the values between FW- and VS-derived TDI examinations (including S′ velocity and the E′:A′ ratio). Single linear regression analysis was used to compare the changes in the echocardiographic measurements with the changes in +dP/dt and –dP/dt values. A value of P < 0.05 was considered significant.
Results
The hemodynamic variables were markedly changed following administration of the inotropic agents (Table 1). Compared with baseline values, dobutamine significantly increased heart rate and LVPS but significantly decreased LVEDP. Similarly, the +dP/dt and –dP/dt were significantly increased by each dose of dobutamine. In contrast, esmolol significantly decreased the LVPS and increased the LVEDP. Similarly, esmolol significantly decreased the +dP/dt and –dP/dt values.
Mean ± SD hemodynamic and LV PWD echocardiographic measurements obtained from 7 healthy dogs at baseline (prior to drug administration) and after 5-minute IV infusions of dobutamine at a rate of 5 or 10 μg/kg/min and esmolol at a rate of 50 or 100 μg/kg/min.
Echocardiographic findings and changes in the PWD measurements under different inotropic conditions were recorded (Figure 2; Table 1). Dobutamine significantly increased the TMF velocities, compared with baseline, whereas esmolol did not. Consequently, neither dobutamine nor esmolol changed the E:A ratio. The IVCT and IVRT were significantly shortened during dobutamine administration, but IVRT was significantly prolonged during esmolol administration. The ET was not changed by dobutamine or esmolol. As a result, the MPI was significantly decreased by dobutamine at each dose, whereas it was significantly increased by esmolol administered at 100 μg/kg/min.
Representative echocardiographic TDI assessments (sample volume positioned at the VS [A–C] and FW [D–F] of the mitral valve annulus) in a healthy dog at baseline (prior to drug administration; A and D), after administration of dobutamine (10 μg/kg/min; B and E), and after administration of esmolol (100 μg/kg/min; C and F). At the top of each view, the corresponding ECG trace is shown. Horizontal markers represent increments of 5 cm/s.
Citation: American Journal of Veterinary Research 68, 10; 10.2460/ajvr.68.10.1051
The TDI profiles were recorded as 1 positive wave (ventricular systole) and 2 negative (early and late) diastolic waves, which were modulated by the β-adrenergic receptor agonist and antagonist. Echocardiographic measurements of the myocardial velocity profiles derived via FW- and VS-TDI were recorded (Table 2). Dobutamine significantly increased the S′, E′, and A′ velocities in the FW- and VS-TDI, compared with baseline. However, administration of esmolol at 100 μg/kg/min significantly decreased the S′ velocity derived via VS-TDI, but the S′ velocity was unchanged via FW-TDI. Following administration of esmolol at 100 μg/kg/min, the FW-TDI–derived E′ velocity was significantly decreased (compared with baseline) but the VS-TDI–derived E′ velocity was unchanged. The A′ velocities were not changed from baseline by esmolol. As a result, the E′:A′ ratio derived via FW-TDI was significantly decreased but the ratio derived via VS-TDI was not changed. Echocardiographic measurements of each duration and MPI derived via FW- and VS-TDI were recorded (Table 3). Dobutamine significantly shortened the IVCT, IVRT, and S′ duration in both the FW- and VS-TDI examinations. The MPI derived via FW-TDI was significantly decreased by dobutamine at 5 μg/kg/min; MPI derived via VS-TDI was significantly decreased by dobutamine at each dose. In contrast, the IVRT was significantly prolonged by esmolol administered at 100 μg/kg/min as determined via VS-TDI, whereas it was not significantly altered by administration of that agent at each dose as determined via FW-TDI. The IVCT and S′ duration were not changed by esmolol in either type of TDI examination. The MPI derived via VS-TDI was significantly increased by esmolol, but that derived via FW-TDI was not.
Mean ± SD echocardiographic variables derived via FW-TDI and VS-TDI performed in 7 dogs at baseline (prior to drug administration) and after 5-minute IV infusions of dobutamine at a rate of 5 or 10 μg/kg/min and esmolol at a rate of 50 or 100 μg/kg/min.
Mean ± SD IVCT, IVRT, S′ wave duration, and MPI derived via FW-TDI and VS-TDI performed in 7 dogs at baseline (prior to drug administration) and after 5-minute IV infusions of dobutamine at a rate of 5 or 10 μg/kg/min and esmolol at a rate of 50 or 100 μg/kg/min.
A comparison between the FW- and VS-TDI data revealed that the S′ velocities derived via FW-TDI were higher than those derived via VS-TDI for each condition (Figure 3). Similarly, for each condition, the E′:A′ ratios derived via FW-TDI were higher, compared with the ratios derived via VS-TDI (Figure 4). The baseline FW-TDI–derived MPI was higher than the values generated by the other techniques, albeit not significantly. The FW-TDI–derived MPI was significantly higher than values generated by the other techniques after administration of each dose of dobutamine. The FW- and VS-TDI–derived MPI values were significantly higher than the PWD-derived MPI following administration of esmolol at 100 μg/kg/min (Figure 5).
Mean ± SD S′ velocities derived via FW-TDI (white bars) and VS-TDI (black bars) performed in 7 dogs at baseline (prior to drug administration; β-Dob and β-Esm) and after 5minute IV infusions of dobutamine (Dob) at a rate of 5 or 10 μg/kg/min and esmolol (Esm) at a rate of 50 or 100 μg/kg/min. *At this time point, the value derived via VS-TDI is significantly (P < 0.05) different from that derived via FW-TDI.
Citation: American Journal of Veterinary Research 68, 10; 10.2460/ajvr.68.10.1051
Mean ± SD E′:A′ ratios derived via FW-TDI and VS-TDI performed in 7 dogs at baseline and after 5-minute IV infusions of dobutamine at a rate of 5 or 10 μg/kg/min and esmolol at a rate of 50 or 100 μg/kg/min. See Figure 4 for key.
Citation: American Journal of Veterinary Research 68, 10; 10.2460/ajvr.68.10.1051
Mean ± SD MPI values derived via PWD echocardiography (gray bars), FW-TDI, and VS-TDI performed in 7 dogs at baseline and after 5-minute IV infusions of dobutamine at a rate of 5 or 10 μg/kg/min and esmolol at a rate of 50 or 100 μg/kg/min. *At this time point, this value is significantly (P < 0.05) different from that derived via PWD echocardiography. †At this time point, this value is significantly (P < 0.01) different from that derived via PWD echocardiography. See Figure 4 for remainder of key.
Citation: American Journal of Veterinary Research 68, 10; 10.2460/ajvr.68.10.1051
Single regression analyses of the dP/dt values and echocardiographic measurements were performed (Table 4). The correlation coefficient between the +dP/dt and the S′ wave velocity was higher for the VS-TDI technique than for the FW-TDI technique. Significant correlation between the +dP/dt and the MPI as determined via VS-TDI, FW-TDI, and PWD was identified. The E:A and E′:A′ ratios were not correlated with the –dP/dt. Significant correlation between the –dP/dt and the E:E′ ratio as determined via FW-TDI was also detected, but that correlation was not evident via VS-TDI. Significant correlation between the –dP/dt and the IVRT as determined via VS-TDI, FW-TDI, and PWD was identified. Significant correlation between –dP/dt and MPI as determined by VS-TDI, FW-TDI, and PWD was also detected.
Results of single regression analyses of dP/dt values and echocardiographic measurements derived via PWD echocardiography, FW-TDI, and VS-TDI performed in 7 clinically normal dogs.
Discussion
It is known that TDI-derived myocardial motion profiles provide detailed information related to LV systolic function as well as diastolic function.12,13 A previous study7 involving dogs with pacing-induced heart failure revealed that the LV ejection fraction and systolic myocardial velocity were decreased significantly and that the LV ejection fraction was closely correlated with the systolic myocardial velocity. Furthermore, the peak systolic myocardial velocity assessed by TDI was useful in the measurement of regional myocardial function. In the dogs of the present study, the S′ velocity was increased by dobutamine and decreased by esmolol (compared with baseline) and it was strongly correlated with +dP/dt. Also, the S′ velocity was more closely correlated with +dP/dt when derived via VS-TDI than via FW-TDI. Thus, our results suggest that the systolic myocardial velocity derived via longitudinal VS-TDI in dogs reflects LV contractility and may provide relatively accurate information. However, Yamada et al13 reported that in humans with chronic heart disease, the systolic myocardial velocity derived from the left ventricular posterior wall closely correlated with the LV ejection fraction and +dP/dt, unlike the systolic myocardial velocity derived from the VS. The discrepancy between the findings of that study and those of the study of this report may be explained by technical differences; the TDI velocities were measured in the parasternal LV short-axis view in the previous study, but we measured the TDI velocities in the apical long-axis view. In addition, heart disease may also account for the differences. Given that TDI-derived myocardial profiles are affected by the relationship between myocardial motion and the angle of the ultrasonic beam, the reliability of TDI velocities depends on the sample position. Therefore, TDI data should be interpreted in terms of the technique applied.
The MPI is a noninvasive PWD echocardiographic measurement that is related to ventricular systolic and diastolic function.10,11 Myocardial performance index values indicate the severity of heart disease and provide prognostic information for conditions such as aortic valve stenosis, dilated cardiomyopathy, and mitral valve regurgitation.14-16 In clinical studies,1,17,18 modified MPI values derived via TDI have been used to evaluate cardiac function in humans and dogs. A major limitation of the PWD-derived MPI is that the IVCT, IVRT, and ET cannot be measured during the same cardiac cycle. Nevertheless, the TDI-derived MPI allows measurement of these intervals during a single cardiac cycle, and evaluation of global cardiac function may be achieved with assessment of the MPI.1,19,20 In another study,19 myocardial infarction in mice was associated with a significant increase in PWD- and TDI-derived MPI values, compared with prestudy values; additionally, assessment of MPI revealed a significant correlation between PWD and TDI, whereas the mean difference between PWD-derived MPI and TDI-derived MPI values was 0.2 ± 0.1.19 In addition, TDI-derived MPI had good correlation with ejection fraction or fractional shortening.19 Because TDI enables clinicians to measure all of those variables within 1 cardiac cycle, TDI-derived MPI may reduce inaccuracies associated with heart rate. The results of the present study have indicated that the FW-derived MPI was higher than the MPI values obtained by use of the other techniques during dobutamine administration and that the TDI-derived MPI was higher than the PWD-derived MPI during esmolol administration. However, the correlation between +/–dP/dt and VS-TDI–derived MPI was higher than that between +/–dP/dt and FW-TDI–derived MPI or PWD-derived MPI. Thus, there is disagreement between the reference ranges calculated by use of various echocardiographic techniques, indicating that clinical assessments of cardiac function through assessment of MPI should be interpreted with caution. Furthermore, in our study, the VS-TDI–derived MPI appears to have provided more accurate information for the evaluation of LV function in dogs than other techniques.
In the present study, the effect of 2 β-adrenergic receptor-modulating agents on TDI profiles was investigated; however, we cannot exclude the possibility that anesthesia may have modulated the TDI in the study dogs. Complete autonomic blockade was not applied in our study, and reflex autonomic changes and loading condition may have affected the filling variables of the heart. It has been reported12 that TDI in dogs is affected by age and body weight. Furthermore, chronic heart disease may also result in different responses to β-adrenergic agents. Therefore, validation of the TDI profiles in response to dobutamine and esmolol will require evaluation of the entire range of responses in conscious dogs with heart disease and in healthy control dogs.
The data obtained in our study indicated that the systolic myocardial velocity is strongly correlated with the +dP/dt in clinically normal dogs. The MPI was significantly correlated with +dP/dt and –dP/dt values via each technique, but the values differed among techniques. Thus, technique-specific reference ranges for TDI-derived MPI should be considered. Furthermore, +dP/dt values had highly correlated with S′ velocity and MPI via longitudinal VS-TDI than via FW-TDI; therefore, of those 2 techniques, VS-TDI may provide additional information regarding LV systolic function in healthy dogs.
ABBREVIATIONS
| TDI | Tissue Doppler imaging |
| LV | Left ventricular |
| dP/dt | First derivative of left ventricular pressure |
| TMF | Transmitral flow |
| E′ | Peak early diastolic flow derived from TDI myocardial velocity |
| MPI | Myocardial performance index |
| VS | Ventricular septum |
| FW | Free wall |
| LVPS | Peak systolic left ventricular pressure |
| LVEDP | End-diastolic left ventricular pressure |
| PWD | Pulsed-wave Doppler |
| E | Peak early diastolic flow derived from PWD-TMF |
| A | Peak late diastolic flow derived from PWD-TMF |
| E:A | E-wave velocity–to–A-wave velocity |
| ET | Ejection time |
| IVRT | Isovolumic relaxation time |
| IVCT | Isovolumic contraction time |
| S′ | Peak systolic flow derived from TDI myocardial velocity |
| A′ | Peak late diastolic flow derived from TDI myocardial velocity |
KV-1a, Kimura Medical Instrument Co LTD, Tokyo, Japan.
COLIN BP-608, Nihon Kohden, Tokyo, Japan.
Millar Instruments, Houston, Tex.
SONOS 5500 system, Hewlett Packard, Palo Alto, Calif.
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