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1First Affiliated Hospital of Fujian Medical University, Fuzhou, China; and 2Methodist DeBakey Heart Center and 3Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas
Submitted 6 June 2005 ; accepted in final form 28 September 2005
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONREFERENCES |
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) was 
50 ms. Its hemodynamic determinants were , LV minimal pressure, and transmitral pressure gradient. In clinical studies, peak acceleration rate of Ea was significantly lower in patients with impaired LV relaxation irrespective of filling pressures (P < 0.001) and with similar accuracy to peak Ea velocity (area under the curve for septal and lateral peak acceleration rates: both 0.78) in identifying these patients. No significant relation was observed between peak acceleration rate and mean wedge pressure. Peak acceleration rate of Ea appears to be a useful index of LV relaxation but not of filling pressures and can be applied to identify patients with impaired LV relaxation irrespective of their filling pressures. heart failure; myocardium; Doppler echocardiography
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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Animal preparation. After the Baylor College of Medicine Animal Research Committee approved the study, 10 healthy adult mongrel dogs (weight 19–28 kg) were anesthetized with pentobarbital sodium (30 mg/kg), intubated, and mechanically ventilated with an external respirator. After a midline sternotomy, the heart was exposed, and after calibration, a high-fidelity 5-Fr pressure catheter (Millar Instruments, Houston, TX) was introduced into the left atrium (LA) through its appendage. Likewise, to measure LV pressures, a calibrated 5-Fr 12-electrode pressure catheter (Millar) was advanced into the LV by crossing the aortic valve (positioned along the LV long axis). Surface electrocardiogram (lead II), atrial, and ventricular pressure signals were simultaneously acquired on a computer-based data-acquisition system, and LA and LV pressures were digitized with recordings acquired at end expiration. The inferior vena cava (IVC) was dissected and a ring was placed around it to allow for gradual occlusion of the vein.
Hemodynamic measurements.
LV minimal pressure and LVEDP, maximal instantaneous diastolic transmitral pressure gradient and LA mean pressure were noted. Also ascertained were the first derivatives of LV pressure in diastole (–dP/dt) and the time constant () of LV relaxation (13).
Echocardiography. The animals were imaged from the epicardium by use of an ultrasound system equipped with TDI capability. In the apical four-chamber view, pulse-wave (PW) Doppler was applied to record mitral inflow at the valve tips (intraobserver variability for measuring mitral peak E velocity: 3 ± 1%). The TD program was applied in PW Doppler to record mitral annular velocities at the septal and lateral areas (6). The peak velocity of Ea (intraobserver variability 5 ± 2%) at the above sites of the annulus was measured under the different loading conditions. The time interval between the peak of R wave and onset of mitral E velocity and between peak of R wave and onset of Ea at the four areas of the mitral annulus were measured. Subsequently the difference between these time intervals (TEa-E) was calculated (10) for each of the four areas and an average value was derived (intraobserver variability 4 ± 2%, interobserver variability 6 ± 2%).
The peak acceleration rate of Ea velocity was derived by the computer after the Ea velocity was traced. The computer algorithm used divided the time from the onset of Ea to its peak into 20 equal intervals and measured the change in velocity per unit of time in each interval and reported the highest value (interobserver variability 8 ± 4%). In an attempt to simplify the measurement of acceleration rate of Ea, we also calculated the mean acceleration rate as the Ea velocity divided by acceleration time. Interobserver variability was 6 ± 3%.
Experimental protocols. Initially LA pressure was increased with intravenous infusion of isotonic saline and decreased with IVC external compression. Both the infusions and compressions were performed in a sequential manner with data acquired at predetermined increments and decrements of mean LA pressure. After achieving a stable hemodynamic state at each LA pressure level, the LA and the LV pressures and Doppler data were acquired. After a stable hemodynamic state was achieved, to evaluate the influence of LV relaxation on Ea and its peak acceleration rate, dobutamine was administered at a dose of 5 µg·kg–1·min–1 with Doppler and pressure data were acquired. Dobutamine infusion was then terminated, and, after the animals returned to their baseline state, esmolol with its negative lusitropic properties was administered (0.5 mg/kg iv) with subsequent reacquisition of data. To assess the possible interaction between atrial pressure and ventricular relaxation on the peak acceleration rate of Ea, fluid administration and IVC compression were repeated during dobutamine and esmolol infusion.
Human Studies
Study group.
The institutional review board of Baylor College of Medicine approved the protocol, and all patients provided written, informed consent. The study sample comprised 190 consecutive patients referred for echocardiographic evaluation at our laboratory. Patients were divided according to the mitral inflow pattern, clinical data, and echocardiographic examination into four groups [control, impaired relaxation (IR), pseudonormal (PN), and restrictive (Res)]. Patients in the control group (n = 55) had no history or evidence of cardiovascular disease with normal LV dimensions, wall thickness, mass, normal PA systolic pressure, and no evidence of significant valvular pathology on echocardiography. The IR group consisted of 41 patients with hypertension, coronary artery disease, and/or LV hypertrophy and a mitral inflow pattern with an early to late transmitral flow velocity (E/A) ratio <1.0. The PN group consisted of 46 patients with symptoms of pulmonary congestion and an E/A ratio 1.0. The Res LV filling group consisted of 48 patients with symptoms of pulmonary congestion and an E/A ratio 2.0.
An additional group of 60 consecutive patients who were undergoing right heart catheterization in the cardiac catheterization laboratory (n = 25) or the intensive care unit (n = 35) was included. All were in sinus rhythm (60–100 beats/min) and with satisfactory Doppler and pressure recordings and no evidence of mitral stenosis, prosthetic mitral valve, or severe mitral regurgitation. Patients had simultaneous echocardiographic and hemodynamic measurements.
Echocardiographic studies. Patients were imaged in a supine position with an ultrasound system equipped with harmonic imaging, a multifrequency transducer, and TDI capability. After acquisition of parasternal and apical views, pulse-Doppler was utilized to record transmitral and pulmonary venous flow in the apical four-chamber view as previously described (8). TDI was applied in the PW mode to record the mitral annular velocities at the septal and lateral areas. Studies were recorded for later playback and analysis.
Echocardiographic analysis. The analysis was performed offline without knowledge of hemodynamic data. LV ejection fraction and LA maximum volume were performed per the recommendations of the American Society of Echocardiography (12). All Doppler values represent the average of three beats. Pulmonary artery (PA) systolic pressure was estimated by using the tricuspid regurgitation jet. Mitral inflow was analyzed for peak E, peak A velocities, E/A ratio, and deceleration time of E velocity. From the pulmonary vein flow velocities, the systolic filling fraction (SFF) and difference in atrial velocity duration between pulmonary vein and mitral inflow (Ar-A) duration were computed (5, 11). Ea and late diastolic mitral annulus velocity by tissue Doppler (Aa) velocities at the two areas of the mitral annulus were measured (septal and lateral). Peak and mean acceleration rates of Ea at septal and lateral sides of mitral annulus were also measured. In addition, the time interval between peak of R wave and onset of mitral E velocity as well as the time interval between peak of R wave and onset of Ea at the four areas of the mitral annulus were measured (10).
Hemodynamic measurements. Hemodynamic data were collected by an investigator unaware of the echocardiographic measurements, at end expiration, and represent the average of five cycles. Mean wedge pressure (PCWP; verified by fluoroscopy, phasic changes in pressure waveforms, and oxygen saturation) was determined using balanced transducers (0 level at midaxillary line).
Statistical analysis. Ea and its peak and mean acceleration rates were correlated with hemodynamic parameters by regression analysis. Stepwise regression was then used to determine the hemodynamic parameters that correlated best with the individual Doppler variables. The study was powered to detect a correlation coefficient of at least 0.4 between the transmitral pressure gradient and peak acceleration rate of Ea (power = 80%, P = 0.05). Repeated-measures ANOVA with Bonferroni correction was used to compare Doppler and hemodynamic parameters at the different lusitropic states (baseline, dobutamine, and esmolol) and loading conditions.
ANOVA with Bonferroni correction was used to compare the control group with each of the other three groups (IR, PN, and Res). Receiver operator characteristic curves were applied to examine the accuracy of TDI signals in identifying patients with increased LV filling pressures. Linear regression analysis was used to relate mean wedge pressure to Doppler measurements. Significance was set at a P value <0.05.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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Hemodynamics and Doppler measurements. Table 1 summarizes the hemodynamic and TD data (average of the two annular sites shown in the table because similar observations were noted at each separate site) at the different experimental stages. Volume expansion resulted in an increase in LV filling pressures, annular Ea, and its peak and mean acceleration rate. IVC occlusion resulted in significantly opposite changes in the above measurements.
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along with an increase in annular Ea and its peak and mean acceleration rate. Esmolol infusion resulted in significantly opposite changes in the above measurements. In all of the above interventions, only esmolol infusion resulted in a significant change in TEa-E, prolonging it.
Relation of TD signals to LV hemodynamics.
In individual dogs, the correlation coefficient of Ea velocity and peak and mean acceleration rate of Ea with LA mean pressure ranged from 0.4 to 0.75 (P value range 0.1–0.03). As for LV relaxation, peak Ea velocity (r = –0.76), and its mean (r = –0.73) and peak acceleration rates (r = –0.75) exhibited strong relations to (all P < 0.001) and –dP/dt (r ranging from 0.65 to 0.79, all P < 0.001) (Fig. 1). Peak and mean acceleration rates of Ea were also significantly related to LV minimal pressure (r = –0.68 and r = –0.65, respectively, both P < 0.01).
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was 50 ms and in those where was <50 ms. There was no significant relation between peak acceleration rate of Ea and the pressure gradient in the stages where 50 ms, whereas a significant positive relation emerged in the stages where was <50 ms (Fig. 2).
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, LV minimal pressure, and transmitral pressure gradient. Human Studies
Clinical characteristics and Doppler echocardiographic variables for the 190 patients, divided into four groups, are listed in Table 2. No significant differences were observed between the four groups in age, heart rate, or blood pressure. The control, PN, and Res groups displayed a higher E velocity, E/A ratio, and a shorter deceleration time compared with the IR group. Mitral inflow, however, did not differentiate between normal and PN groups. However, as previously reported, LA volume, PA systolic pressure, pulmonary venous SFF, and Ar-A duration were useful in that regard (see Table 2).
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Similar to peak Ea velocity, peak and mean acceleration rate of Ea were significantly lower in patients with PN and Res LV filling compared with controls (ANOVA, P < 0.001; Bonferroni t-test P < 0.05 for control group vs. each of the other three groups). Figure 3 illustrates examples of TDI signals in four representative cases. Table 3 summarizes the accuracy of peak Ea velocity and its acceleration rate in identifying patients with impaired LV relaxation despite elevated filling pressures (ROC curves shown in Fig. 4).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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Animal Studies
We used the PW signal at each side of the mitral annulus to calculate the peak acceleration rate of Ea. PW, unlike color Doppler, has the major advantage of superior temporal resolution, which suits well the need to calculate the peak acceleration rate given the very short time (frequently <50 ms) when acceleration of Ea is occurring. An additional advantage to our method lies in the higher sampling rate afforded by using 20 intervals for deriving the peak acceleration rate, making it much less likely to miss the highest acceleration rate when limiting the analysis to longer time intervals.
In the previous study (4), the peak acceleration rate of the Ea velocity, particularly at the septal side of the mitral annulus, increased significantly with blood infusion but was not altered by dobutamine or metoprolol administration. Unlike these findings, we noted that changes in the myocardial lusitropic state with either dobutamine or esmolol were effective in producing significant changes in peak acceleration rate of Ea. The magnitude of change in Ea peak acceleration rate was comparable to the change in peak Ea velocity induced by these drugs. Furthermore, the peak acceleration rate of Ea had a significant inverse correlation with the invasive measurements of LV relaxation that was almost identical to those of Ea peak velocity.
The relation between the peak acceleration rate of Ea and filling pressures is a complicated one and overall very similar to that of the peak Ea velocity itself, as previously reported in animal (3, 7) and human studies (1, 2). The relation between LA pressure and peak acceleration rate of Ea in the presence of cardiac dysfunction is very important for the clinical application of Ea acceleration rate in the clinical setting, because the assessment of LV filling pressures is frequently needed in patients with cardiac disease. The previous animal work was limited in that regard owing to the occurrence of only small changes in LA pressure with beta-blockers. However, the peak acceleration rate of Ea can be used to predict LV filling pressures in normal subjects, given the direct relation between this Doppler measurement and preload in normal states.
On the other hand, our animal study provides the pathophysiological reasons for not applying the peak acceleration rate of Ea to the estimation of LV filling pressures, in the presence of impaired LV relaxation (Fig. 2). Similar to the acceleration rate of Ea, TEa-E duration was altered by esmolol, but, unlike the acceleration rate, IVC occlusion and volume infusion had no significant effect on this time interval. Overall these results are similar with the observations of Hasegawa et al. (3), who noted that Ea was progressively delayed after LA to LV pressure crossover and was significantly related to in an animal model of pacing-induced heart failure.
Human Studies
In the human studies, the mean and peak acceleration rate of Ea at either side of the mitral annulus were significantly lower in patients with impaired LV relaxation, irrespective of LV filling pressures. It is interesting that the relation between mean wedge pressure and peak acceleration rate of Ea, shown in Fig. 5, in patients with cardiac disease was very similar to that observed in the canine experiments between transmitral pressure gradient and peak acceleration rate of Ea when LV relaxation was impaired as shown in Fig. 2 (dashed line and open circles).
Our study also shows that the accuracy of peak acceleration rate of Ea at either side of the mitral annulus for identifying patients with impaired LV relaxation despite elevated filling pressures (PN and Res groups) is similar to that of the peak Ea velocity. There was no incremental information gained over peak Ea velocity by measuring its acceleration rate. Given the above findings and the complexity of measurement of acceleration rate, peak Ea velocity rather than its acceleration rate is more suitable for the daily application in the laboratory.
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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