Effect of Preload Alterations on Left Ventricular Systolic Parameters Including Speckle-Tracking Echocardiography Radial Strain During General Anesthesia Ulrike Weber, MD,* Eva Base, MD,* Robin Ristl, PhD,† and Bruno Mora, MD, PhD* Objectives: Frequently used parameters for evaluation of left ventricular systolic function are load-sensitive. However, the impact of preload alterations on speckle-tracking echocardiographic parameters during anesthesia has not been validated. Therefore, two-dimensional (2D) speckle-tracking echocardiography radial strain (RS) was assessed during general anesthesia, simulating 3 different preload conditions. Design: Single-center prospective observational study. Setting: University hospital. Participants: Thirty-three patients with normal left ventricular systolic function undergoing major surgery. Interventions: Transgastric views of the midpapillary level of the left ventricle were acquired at 3 different positions. Measurements and Main Results: Fractional shortening (FS), fractional area change (FAC), and 2D speckle-tracking echocardiography RS were analyzed in the transgastric midpapillary view. Considerable correlation above 0.5 was found for FAC and FS in the zero and Trendelenburg
positions (r ¼ 0.629, r ¼ 0.587), and for RS and FAC in the anti-Trendelenburg position (r ¼ 0.518). In the repeatedmeasures analysis, signiﬁcant differences among the values measured at the 3 positions were found for FAC and FS. For FAC, there were differences up to 2.8 percentage points between the anti-Trendelenburg position and the other 2 positions. For FS, only the difference between position zero and anti-Trendelenburg was signiﬁcant, with an observed change of 1.66. Two-dimensional RS was not signiﬁcantly different at all positions, with observed changes below 1 percentage point. Conclusions: Alterations in preload did not result in clinically relevant changes of RS, FS, or FAC. Observed changes for RS were smallest; however, the variation of RS was larger than that of FS or FAC. & 2015 Elsevier Inc. All rights reserved.
cardiac patients with valve replacement,13 after myocardial infarction,6,7 or in resynchronization therapy.14 Strain measurements have been validated against magnetic resonance data and correlate with each other.15,16 The feasibility of performing strain analysis in the operating room has been reported by Suffoletto et al and Domanski et al.14,17 However, the correlation between TEE and TTE for radial strain has been reported differently.18 The aim of this study was to compare 3 echocardiographic parameters for evaluation of left ventricular function during acute alterations of preload induced by different positions of the patient on the operating table (zero, Trendelenburg, and anti-Trendelenburg). In particular, FS and FAC, as well as 2D RS, were measured by TEE in the transgastric midpapillary short-axis view in patients undergoing major abdominal surgery under general anesthesia.
NTRAOPERATIVE TRANSESOPHAGEAL echocardiography (TEE) has become a well-established monitoring technique and not only during cardiac surgery. It also is used increasingly during major general surgery, because the method is only semi-invasive and has a very low number of complications.1 TEE allows quick assessment of left ventricular systolic function as a key parameter for cardiac performance. Echocardiographic parameters for evaluation of left ventricular function include fractional shortening (FS) and fractional area change (FAC), which can be performed easily and quickly in the transgastric midpapillary short-axis view.2 However, FS and FAC have some limitations; one is that they are loadsensitive measures.3 During anesthesia and surgery, load conditions may change quickly because of alterations in ﬂuid status, anesthetic drugs, and surgical manipulations. Two-dimensional strain echocardiography (2DSE) is a newer method for assessment of myocardial function and is based on measurement of myocardial deformation using speckle tracking from B-mode images.4,5 Radial strain (RS) measurements derived from 2DSE provided incremental beneﬁt when compared with conventional measures of regional function in the assessment of ischemic heart disease.6–12 In addition, several studies have investigated 2D speckle-tracking radial strain in
From the *Department of Anaesthesiology, General Intensive Care and Pain Control, Medical University of Vienna, Vienna, Austria; and †Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria. Address reprint requests to Ulrike Weber, MD, Department of Anaesthesiology, General Intensive Care and Pain Control, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. E-mail: [email protected]
© 2015 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.12.015 852
KEY WORDS: transesophageal echocardiography, speckle tracking, radial strain
This prospective observational single-center study was performed in accordance with the Declaration of Helsinki and approved by the Ethical Committee of the Medical University Vienna, Austria (registration number: 787/2009). The study was registered at clinicaltrials.gov (registration number: NCT01080495; registrar: Ulrike Weber, MD). Thirty-three patients undergoing surgery with a minimum duration of 30 minutes and requiring intubation of the trachea were included. Exclusion criteria were reported as impaired left ventricular function, valve disease, rhythm abnormalities, and any contraindications for TEE. All patients received routine monitoring with an arterial catheter. In 4 patients, a central venous catheter was inserted when clinically indicated. The anesthetic technique was general endotracheal anesthesia. TEE studies were performed in the supine position after induction of a propofol- and fentanyl-based anesthesia, which was maintained with sevoﬂurane. Standard vital parameters were recorded continuously.
Journal of Cardiothoracic and Vascular Anesthesia, Vol 29, No 4 (August), 2015: pp 852–859
PRELOAD ALTERATIONS AND LEFT VENTRICULAR SYSTOLIC PARAMETERS
TEE was performed with a Vivid 7 Ultrasound system (GE Vingmed; Horten, Norway) using a cT6 (3.0-8.0MHz, GE) probe. A standard greyscale 2D image was acquired in the midpapillary short-axis view. Penetration, resolution, and gain were optimized for each patient, and the frame rate was 80 frames per second. Imaging frequency ranged between 5 and 7 Megahertz. The midpapillary short-axis view was recorded at 3 different time points, and at each time point, patients were positioned in a different way by tilting the operating table. Positions were deﬁned as zero position (horizontal), Trendelenburg position, (10-cm head-down from horizontal position), and anti-Trendelenburg-position (10-cm head-up from horizontal position). Sequence of positioning followed a random order according to a blinded randomization list. Three cardiac cycles of the transgastric midpapillary short-axis view were stored in the cine-loop format for each position. All data were transferred to a workstation for further analysis (Echo PAC 6.1, GE Vingmed Ultrasound). All TEE studies and analyses were performed by one single operator (Bruno Mora). FS and FAC were calculated by standard formulae.2 Twodimensional radial strain analyses were performed on the same 2D greyscale images. A region of interest was traced on the endocardial cavity interface by a point-and-click approach from an end-systolic single frame. Speckle-tracking echocardiography (STE) software automatically divided the left ventricle (LV) into 6 equal segments, in accordance with the standardized myocardial segmentation model.19 An automated tracking algorithm followed the endocardium from this single frame throughout the cardiac cycle.20 Left ventricular function was measured using 3 different methods with metric outcomes FAC, FS, and RS. Each measurement was repeated 3 times in each of the 3 positions: Zero, Trendelenburg, and anti-Trendelenburg. STATISTICAL ANALYSIS
The primary aim was to analyze the correlation among the values obtained by the 3 methods within each position, and the secondary aim was to analyze the differences among obtained values among positions. To detect a correlation of rho ¼ 0.5 (power 80%, level of signiﬁcance 0.05, two-sided) and a dropout rate of 10%, a sample size of 33 patients was required. The sample size also was sufﬁcient to accomplish the secondary aim. Using a paired t test as the most simple form of a repeated-measures analysis, 30 patients resulted in a power of 80% to detect a mean difference of 0.53 standard deviations (of the difference) at a 0.05 level of signiﬁcance. Correlations were described by scatterplots for each pairwise combination of measurement results and by calculating Spearman’s correlation coefﬁcients. Differences between the positions were analyzed by repeated-measures analysis in terms of linear models allowing for an unstructured covariance matrix, thus accounting for correlations of observations within the same individual and considering different variances and covariances for each position and combination of positions. From these models, a global F-test for the null hypothesis of no difference between any positions was calculated for each echocardiographic parameter.
The mean differences and 95% conﬁdence intervals were calculated for each pairwise combination of the 3 positions. Further, within-patient differences in radial strain values among 6 segments of the left ventricle (anterior, anteroseptal, anterolateral, inferolateral, and inferoseptal) were analyzed. The analysis was done for each of the 3 positions: Zero, Trendelenburg, and anti-Trendelenburg positions. Differences in mean RS among the 6 LV segments were analyzed by a repeated-measures analysis in terms of linear models, again using an unstructured covariance matrix. The null hypothesis of no mean within-patient differences among the segments was tested from the resulting models. For descriptive statistics, metric variables were described by mean, standard deviation, minimum, and maximum. Categoric variables were described by absolute and relative frequencies. Statistical analysis was performed with SAS 9.3 software (SAS Institute Inc., Cary, NC), using PROC MIXED for the repeated measures analysis. RESULTS
Of the 33 patients studied, adequate image quality was available from 28 patients for the zero position (84.8%), from 27 patients (81.8%) for the Trendelenburg position, and from 30 patients (90.9%) for the anti-Trendelenburg position. No adverse events or hemodynamic instability was observed in any patient. Table 1 presents the demographic parameters of all 33 patients included in the study. Table 2 summarizes the blood pressure and heart rate values, as well as the echocardiographic parameters fractional shortening, fractional area change, and 2D radial strain in the 3 different positions. Because image quality was inferior in some cases, all of the 297 images could not be included in the ﬁnal analysis. Table 2 shows the measurements that were used: 33 measurements for FS and FAC and 28 for RS in the zero position, 33 measurements for FS and FAC and 27 for RS in the Trendelenburg position, and 33 measurements for FS and FAC and 30 for RS in the anti-Trendelenburg position. In total, 283 images were obtained and evaluated for this study. Blood pressure values were higher in the zero position compared with the other 2 positions, and the lowest values were observed in the anti-Trendelenburg position. Table 3 shows the mean differences of FS, FAC, and RS, respectively, among the 3 positions; 95% conﬁdence intervals for these differences are included, as well as a p value for the test of the null hypothesis of no differences among any positions. Signiﬁcant differences among the positions were found for FS and FAC, but not for RS. Fractional shortening and fractional area change were lowest in the anti-Trendelenburg position, compared with the other 2 positions, which had Table 1. Demographic Parameters
Age (yrs) Gender/Male Height (cm) Weight (kg)
Mean ⫾ SD Frequency (%)
54.7 ⫾ 13.03 33/18 (55%) 172.33 ⫾ 8.14 70.39 ⫾ 14.98
26-77 155-194 43-105
NOTE. Values are presented as mean with standard deviation, or absolute and relative values and minimum to maximum values. Abbreviation: SD, standard deviation.
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Table 2. Average Hemodynamics and Echocardiographic Parameters During the Three Positions
Zero position MAP (mmHg) sysBP (mmHg) diaBP (mmHg) Heart rate (bpm) FS (%) FAC (%) RS (%) RS (%)* Trendelenburg position MAP (mmHg) sysBP (mmHg) diaBP (mmHg) Heart rate (bpm) FS (%) FAC (%) RS (%) RS (%)* Anti-Trendelenburg position MAP (mmHg) sysBP (mmHg) diaBP (mmHg) Heart rate (bpm) FS (%) FAC (%) RS (%) RS (%)*
Mean ⫾ SD
33 33 33 33 33 33 28 28
84.2 ⫾ 20.23 109.6 ⫾ 25.53 68.3 ⫾ 17.73 69.9 ⫾ 11.6 30.6 ⫾ 4.16 57.33 ⫾ 4.2 51.58 ⫾ 8.42 51.79 ⫾ 9.29
58-135 73-169 48-118 50-97 21.33-43 48.03-68.33 36.92-66.75 36.92-66.75
33 33 33 33 33 33 27 27
77.3 ⫾ 15.82 103.4 ⫾ 21.23 61.4 ⫾ 13.3 67.7 ⫾ 11 30.02 ⫾ 4.55 58.09 ⫾ 4.19 50.6 ⫾ 7.88 50.93 ⫾ 6.77
50-132 73-186 37-95 43-90 21.33-47 48.03-72 38.25-71 38.25-71
33 33 33 33 33 33 30 30
74.7⫾ 12.21 99.2⫾ 14.85 59.4 ⫾ 10.55 68.4 ⫾ 11.3 28.94 ⫾ 3.81 55.3 ⫾ 3.51 50.93 ⫾ 10.98 50.84 ⫾ 10.93
57-110 77-143 43-87 48-90 20-36 47.48-62.33 32-80.59 32-80.59
NOTE. Values are presented as mean with standard deviation and minimum-maximum values. Abbreviations: diaBP, diastolic blood pressure; FAC, fractional area change; FS, fractional shortening, MAP, mean arterial pressure; SD, standard deviation; sysBP, systolic blood pressure; RS, radial strain. * Mean RS estimated from the mixed model. This estimate uses the observed RS values from all 3 positions and the within-patient correlation of these measurements. It is the appropriate estimate to analyze within-patient differences and leads to the results in Table 3.
similar values. Scatterplots of measured variables within each position are shown in Figures 1, 2, and 3. Considerable correlation above 0.5 was found for FAC and FS in positions zero and Trendelenburg, as well as for RS and FAC in the anti-Trendelenburg position. When comparing the RS measurements from the 6 heart segments, no signiﬁcant differences were found for either position (p values were 0.3047, 0.1901, and 0.1739 for the Zero, the Trendelenburg, and anti-Trendelenburg positions, respectively). This result is illustrated in Figure 4, which shows the observed RS values for each patient across the LV segments, as well as the mean and 95% conﬁdence intervals for the mean in each segment. DISCUSSION
In the present study, the potential use of radial strain by 2D STE in the evaluation of left ventricular function during alterations of preload in anesthetized patients for major noncardiac surgery was demonstrated. The study speciﬁcally focused on comparison of the conventional parameters, FS and FAC, and the newer parameter, 2D speckle-tracking radial strain. The principal results showed that changes due to alterations of preload in 2D-RS, FS, and FAC were close to zero. The observed changes were on the order of magnitude of 1 to 2 percentage points; Table 3 shows the point estimates and
conﬁdence intervals. For FS and FAC, some differences were signiﬁcantly different from zero; however, the conﬁdence intervals showed that the true effects can be assumed to be too small to implicate clinical importance. The increasing uses of intraoperative echocardiography necessitate precise parameters for evaluation of left ventricular function during different loading conditions. Preload alterations occur frequently in the operating room for several reasons (eg, different positions, bleeding of varying extent, and volume displacements). Afterload changes are induced by anesthetic drugs, which cause vasodilatation and, subsequently, volume displacements and preload changes. Several studies on animals21,22 and in human subjects23 have shown that strain and strain rate are highly load-dependent parameters. Weidemann et al measured radial strain and strain rate using a tissue Doppler imaging (TDI)-based technique in a porcine model and reported that radial strain reﬂects changes in stroke volume. They altered loading conditions with atrial pacing, esmolol, and dobutamine infusions.21 Rosner et al showed, in a porcine model, that colloid infusion led to increased strain and strain rate associated with increased end-diastolic pressure.22 Burns et al performed simultaneous Millar micromanometer LV pressure and echocardiographic assessment on 18 patients with normal left ventricular function using glyceryltrinitrate and saline
PRELOAD ALTERATIONS AND LEFT VENTRICULAR SYSTOLIC PARAMETERS
Table 3. Estimates of the Mean Difference in Fractional Shortening, Fractional area change, and 2D Radial Strain
FS (%) FAC (%) RS (%)
Zero Position – Trendelenburg
Zero Position – Anti-Trendelenburg
Trendelenburg Position – Anti-Trendelenburg
0.58 (–0.32, 1.49) p ¼ 0.199 –0.76 (–1.65, 0.13) p ¼ 0.092 0.77 (–2.65, 4.20) p ¼ 0.648
1.66 (0.43, 2.89)* p ¼ 0.010 2.04 (0.6, 3.47)* p ¼ 0.007 0.65 (–3.81, 5.12) p ¼ 0.767
1.08 (–0.29, 2.44) p ¼ 0.118 2.79 (1.25, 4.33)* p ¼ 0.001 –0.12 (–4.26, 4.02) p ¼ 0.953
0.027 0.003 0.896
p Value Global
NOTE. Estimates of the mean difference of FS, FAC, and 2D RS among the 3 loading positions are shown. The 95% conﬁdence intervals are listed in parenthesis. The p value for the global test refers to the global null hypothesis of no mean difference between any of the positions. Abbreviations: 2D, two-dimensional; FAC, fractional area change; FS, fractional shortening, RS, radial strain. * p o 0.05 for direct comparisons between positions.
ﬂuid loading to alter loading conditions and found that circumferential and longitudinal peak strain and strain rate were sensitive to acute changes in load.23 Radial strain—not longitudinal or circumferential strain— was compared with FS and FAC. The rationale for this was that measuring RS is easier and quicker to perform and all 3 measurements could be performed on one imaging plane (eg, the midpapillary short-axis view). Because radial thickening in systole is 40%, which is accompanied by 14% longitudinal shortening,3,24 radial strain is of clinical relevance. However, compared with FS, performing measurements in only one imaging plane is less representative for overall LV systolic function. Furthermore, to the authors’ knowledge, no software is available to calculate longitudinal and circumferential strain directly from TEE images. In addition, great variability in the ability to obtain adequate images for analyzing radial strain has been reported.25 Values for radial strain ranged from 35.1% to 59.0 % (mean 47.3%;
conﬁdence interval 43.6% to 51%) even in healthy individuals.25 In addition, inferior interobserver variability of radial strain compared with longitudinal strain has been shown.26 The feasibility of performing STE using transgastric TEE images has been explored in a limited number of studies.4,18,27 Although Kukucka et al4 and Marcucci et al18 found acceptable success rates, success rates were much lower in the study by Wang et al.27 The higher success rates in the present study probably were due to having a noncardiac surgery patient population before any surgical manipulation, in which technical problems for the ultrasound system were marginal. In addition, the patient population was homogenous with normal cardiac function. From a clinical standpoint, radial strain is quick and easy to perform, which is important in such a rapidly changing setting as the operating room. However, there are important technical limitations to take into consideration. Strain and strain rate can be measured either by speckle-tracking imaging (STI), as in the
Fig 1. Scatterplot of measured variables within the zero position. Correlation (r) with p values (p) for FS, FAC, and RS. Abbreviations: FAC, fractional area change; FS, fractional shortening; RS, two-dimensional radial strain.
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Fig 2. Scatterplot of measured variables within Trendelenburg position. Correlation (r) with p values (p) for FS, FAC, and RS. Abbreviations: FAC, fractional area change; FS, fractional shortening; RS, two-dimensional radial strain).
Fig 3. Scatterplot of measured variables within anti-Trendelenburg position. Correlation (r) with p values (p) for FS, FAC, and RS. Abbreviations: FAC, fractional area change; FS, fractional shortening; RS, two-dimensional radial strain).
PRELOAD ALTERATIONS AND LEFT VENTRICULAR SYSTOLIC PARAMETERS
Fig 4. Trajectories of RS values across the 6 segments of the left ventricle for zero, Trendelenburg, and anti-Trendelenburg positions. Trajectories for individual patients are shown as grey lines, mean values are shown as black lines, and vertical bars correspond to 95% conﬁdence intervals for the mean in each segment. Abbreviations: Ant, anterior; ant-sept, anteroseptal; ant-lat, anterolateral; inf-lat, inferolateral; inf-sept, inferoseptal.
present study, or by TDI. STI correlates well with invasive gold standard measures, such as sonomicrometry.28–30 STI is not angle-dependent, compared with TDI, but is highly sensitive to image quality.31 In addition to these resolution issues, a limited amount of tissue to track in the short-axis view of nonhypertrophied hearts might be a problem.25 Furthermore, placement of the region of interest may affect strain amplitude. To limit these issues in the present study, all measurements were performed by one person, and still the variability of RS values was much greater than the values for FS and FAC. In addition, when measuring RS separately in all 6 segments, similar values for each segment were obtained, which is illustrated in Figure 4. This showed that there was no bias due to the alignment of the ultrasound beam and that good image quality was obtained. These calculations were performed to exclude any kind of bias and
to demonstrate the reliability of radial strain in all segments. Analyzing the 6 segments separately minimized the potential error of technical limitations in some segments. The authors acknowledge that the present study had several limitations. Preload alterations were induced by a deﬁned change in the patient's position. An exact amount of ﬂuid was not administered, but signiﬁcant increases in stroke volume in response to head-down tilt have been shown.32 The assumption of a virtual ﬂuid challenge equivalent to approximately 500 mL is common among anesthesiologists and intensivists.33 Other studies used administration of ﬂuid bolus, glyceryltrinitrate, esmolol, or dobutamine to alter preload,22,23 which might have been more effective, considering the fact that signiﬁcant changes in blood pressure and heart rate were not
WEBER ET AL
observed. This method of altering preload was chosen for 2 reasons. First, changes in patient position are very common during general anesthesia for major surgery, and second, recent studies reported that the Trendelenburg and the antiTrendelenburg positions are effective for studying effects of cardiac preload in anesthetized and mechanically ventilated patients.34–36 Another limitation was the fact that there were no accurate and invasive measurements of loading conditions performed, such as stroke volume index by pulmonary artery catheter or left ventricular pressures by cardiac catheterization. The study was restricted to a small group of patients with normal left ventricular function in whom invasive monitoring such as a pulmonary artery catheter could not be justiﬁed. In the patients who received a central venous catheter, central venous pressure values were not recorded at the same time that echocardiographic measures were taken. The lack of central venous pressure values is a limitation when preload alterations are studied. However, insertion of a central venous catheter was performed only when clinically necessary and not for study purpose. Another limitation of the study was the exclusive inclusion of patients with normal left ventricular function. The authors did not assess patients with different levels of myocardial
function and regional wall motion abnormalities. Given the wider range of 2D RS measurements compared with FS and FAC in patients with normal left ventricular function, the authors expected even fewer signiﬁcant differences in patients with impaired left ventricular function. All echocardiographic measurements and analyses were performed by a single operator; therefore, interobserver variability was not taken into account. The authors believe that this limitation should not be a bias, especially with regard to FS, because some textbooks and manuscripts describe the measurements with M-mode and 2D images as fairly reproducible with low interobserver variability.37–40 CONCLUSIONS
The echocardiographic parameters FS and FAC showed some statistically signiﬁcant differences between loading conditions. However, they were small and likely of minor clinical importance. The greater variability of 2D RS measurements does not provide additional clinical information. Taking into account the necessity of off-line analysis, the usefulness remains questionable.
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