- Top of page
- Material and Methods
Background: Stress echocardiography is used to diagnose myocardial dysfunction in horses, but current methods are not well standardized. The influence of heart rate (HR) on measurements is largely unknown.
Objectives: To investigate the use of 2-dimensional echocardiography (2DE), anatomical M-mode (AMM), tissue Doppler imaging (TDI), and 2D speckle tracking (2DST) at rest and after exercise for quantification of regional and global left-ventricular (LV) function.
Animals: Five athletic Warmblood horses; 11.6 ± 3.6 years; 529 ± 48 kg.
Methods: Prospective study. Three separate echocardiographic examinations were performed before (baseline) and over 5 minutes after treadmill exercise with 2DE (1st, short-axis view; 2nd, long-axis view) and pulsed-wave TDI (3rd examination). Offline analyses were performed at baseline and after exercise at HR 120, 110, 100, 90, and 80 minute−1. Global and segmental measurements were compared by analysis of variance.
Results: Quantitative analyses of stress echocardiograms were feasible in all horses. None of the AMM indices changed significantly after exercise. Stroke volume and ejection fraction by 2DE and strain by 2DST decreased, whereas strain rate by 2DST increased significantly at HR > 100 minute−1. TDI analyses were technically difficult and provided little additional information.
Conclusions and Clinical Importance: Volumetric indices by 2DE and strain and strain rate by 2DST are applicable for quantitative assessment of stress echocardiograms. In healthy horses, they are significantly altered at a HR > 100 minute−1 and need to be evaluated in view of the instantaneous HR. Further investigations are needed to define the clinical value of stress echocardiography in horses with cardiac disease.
Heart disease is recognized as a potential cause of exercise intolerance and poor performance in athletic horses.1 The diagnosis of performance-limiting heart disease is complicated by the high prevalence of heart murmurs and of valvular regurgitation detected by color Doppler echocardiography in apparently healthy horses.2,3 Furthermore, myocardial disease can exist in the absence of murmurs or dysrhythmias and might therefore be underrecognized.4,5 Despite recent advances in cardiovascular diagnostics, it is often difficult to prove an etiologic relationship between echocardiographic findings and impaired athletic performance unless severe valvular regurgitation, significant chamber enlargement, obvious myocardial dysfunction, or marked cardiac dysrhythmia can be diagnosed.
Stress echocardiography has gained interest in equine medicine, with the goal to diagnose stress-induced myocardial dysfunction.4,6–12 However, the incidence of exercise-induced myocardial ischemia is largely unknown in horses, the target diseases to be detected are not well defined, and the indications for stress echocardiography and its clinical value in horses are still unresolved. Furthermore, there is a paucity of standardized and objective methods for assessment of left-ventricular (LV) function after stress induction in horses.
Quantitative assessment of global LV function after exercise is currently limited to measurement of chamber dimensions and calculation of ejection phase indices derived from 2-dimensional (2D) or M-mode images. However, the current literature is inconsistent in regards to the time course of commonly used measurements after treadmill exercise,4,6,9,11 suggesting that many of them might not be suitable for quantitative assessment of stress echocardiographic studies. Assessment of regional myocardial function is even more difficult. It has been achieved by manual tracking of endocardial motion and subjective evaluation of regional wall motion.4,12,13 However, truly quantitative approaches have not been established in horses.
Finally, the influence of heart rate (HR) on echocardiographic indices of cardiac function has not been thoroughly investigated to date,4,6,9,11 although it is generally recommended to perform stress echocardiography in horses immediately after cessation of treadmill exercise, at an HR above 100 minute−1.4
Advanced echocardiographic techniques might serve to overcome some of the current limitations of equine stress echocardiography. Anatomical M-mode (AMM)a allows offline analysis of conventional 2D cineloop recordings, reducing the time required for data collection.14,15 Area-based measurements allow assessment of shortening in two dimensions and are less sensitive to asynchronous wall motion,16,17 while volume-based indices are generally considered most accurate and least affected by altered chamber geometry.16–19 Tissue Doppler imaging (TDI) has recently been used to study left atrial and LV wall motion in resting horses20–23 and might serve to quantify LV systolic and diastolic function and to detect occult myocardial disease.24–29 Finally, 2D speckle tracking (2DST) allows quantitative assessment of regional and global systolic LV wall motion in longitudinal and radial direction based on conventional 2DE cineloop recordings.24,30–32
The goal of this study was to investigate the changes over time of echocardiographic indices of LV systolic function within the 1st 5 minutes after cessation of a standardized treadmill exercise test in athletic horses using 2DE, AMM, TDI, and 2DST. The influence of HR on indices of LV function was investigated, to determine the potential clinical value of each index and to identify a HR limit above which stress echocardiography should be performed. We hypothesized that the indices of LV function largely depend on HR and are highly variable within the first 5 minutes after treadmill exercise.
- Top of page
- Material and Methods
The results of this study show that quantitative analysis of stress echocardiograms in horses after high-speed treadmill exercise is feasible using 2DE, AMM, and 2DST, while the application of TDI is technically difficult and inaccurate. Some of the investigated echocardiographic indices are able to detect consistent alterations in LV function after cessation of exercise.
The availability of accurate and reliable methods for assessment of global and regional cardiac function is crucial to study the clinical value of stress echocardiography in horses. Currently, routine imaging methods used for assessment of global LV function rely on 2DE, M-mode, and flow Doppler methods.16–19,34 Most commonly, ejection phase indices are calculated from one-dimensional M-mode measurements of LV dimensions, with the FS being the only index routinely used in horses.16–18 However, reliance on the FS as a single index of LV systolic function is problematic, because it represents the shortening of the LV in a single dimension, disregarding the fact that the LV contracts in all three dimensions. Also, it lacks accuracy in the presence of ventricular dyssynchrony, regional wall motion abnormalities, or malposition of the cursor line. It is therefore not surprising that there is disagreement in the current literature regarding the time course after treadmill exercise of LV FS and other conventional 2DE and M-mode indices in horses.4,6,9,11 The results of this study revealed that AMM and—for most instances—area-based indices of LV dimensions and LV systolic function are generally not suitable to detect exercise-induced changes in LV function. Among the area-based indices, only MWTA FC/EMS, reflecting myocardial deformation rate, increased significantly in the immediate postexercise period, mostly because of the observed shortening of EMS.
Volumetric estimates of LV size and function are considered more accurate and less affected by altered chamber geometry than linear indices.35,36 The volumetric LV EF is a standard index of LV systolic function in humans. It is not commonly used in horses, mostly because many of the required imaging planes are difficult to obtain in large animals.16 Furthermore, all volumetric indices are calculated based on geometrical assumptions and approximations, limiting their accuracy.16–18 Despite these restrictions, the results of the current study suggest that volumetric estimates of LV dimensions and function obtained from LAX views are superior to linear and area-based SAX indices in identifying exercise-induced changes of LV function in healthy horses after treadmill exercise. This can be explained by the large impact of ventricular length on volumetric LV estimates by Simpson's method. The results therefore indicate that systolic length of the LV increased after exercise (data not shown), concordant to the decrease of DL−sys after exercise. These findings support the contention that LAX motion of the LV is an important component of LV function37 that undergoes dynamic changes during and after exercise, while adaptations in radial (SAX) motion only play a minor role.
The LVIVs increased and the SV and EF decreased significantly after exercise compared with baseline, whereas the CO, because of the high HR, increased significantly. Although these findings seem counterintuitive, they were similar to the results of a study in ponies, in which systolic shortening measured by ultrasonic crystals increased during exercise but was significantly reduced after exercise.38 The slight but not significant decline in end-diastolic LV dimensions is suggestive of an exercise-induced decrease in ventricular filling, most likely related to the increase in HR that shortens diastolic ventricular filling time. This could explain the decrease in SV at higher HR.39 Most likely, other factors related to rapidly changing autonomic input, preload, afterload, contractility and their complex interrelation also play a role during the immediate postexercise period.
Quantitative characterization of LV wall motion in horses has recently been investigated using tissue velocities by TDI23 as well as strain and strain rate by 2DST.32 The results of the current study showed that Sm and PEP/ET increased after exercise while ET decreased at higher HR because of the shortening of the ejection period. The significant increase in Sm is in accordance to studies in people, indicating an increase in LV systolic performance during and after exercise.40–43 The significant increase in PEP/ET can be explained with the increase in HR and the slight but not significant decrease in preload (reflected by LVIVd).16,44 None of the other TDI variables changed consistently and significantly after exercise. However, only Sm and Em were identifiable in all horses and throughout all HR, while difficulties in identifying velocity waves at higher HR often precluded the measurement of S1, E1, IVRT, and IMP. The low number of measurements during isovolumic periods might be responsible for the inability to detect significant changes after exercise.
Assessment of diastolic LV function is difficult in horses. While 2DST is considered unreliable for assessment of radial LV diastolic wall motion,32 TDI allows reliable assessment of diastolic LV wall motion in horses at rest.23 The results of this study showed that, in agreement with previous studies in people,42,43 both Em and Am by PW TDI increased after exercise. However, fusion of Em and Am waves40,45 was seen at HR120 and HR110 and therefore prevented their measurement in the majority of horses. Furthermore, Em and Em+ Am, respectively, exceeded the maximum velocity scale at higher HR. The value of PW TDI for quantitative stress echocardiography is therefore highly limited. If to be used at all, its use should be limited to the measurement of systolic Sm and PEP/ET. It is unknown if color TDI (cTDI) would have offered some additional value over PW TDI. In a previous study in horses, cTDI did not provide substantial advantages over PW TDI for analysis of radial LV wall motion velocities and it was less reliable, particularly pertaining to strain and strain rate analyses.23
Wall motion analysis by 2DST is considered superior to TDI because of its independence of the angle of interrogation and the ability to assess segmental myocardial motion in two dimensions simultaneously.24,31,32,46 The results of this study showed that both ɛR and ɛL by 2DST decreased after exercise. This finding is in agreement with the decrease in SV and EF, supporting the contention that strain is an analog of regional EF and largely reflects changes in SV.25,47,48 The SRR−sys and the SRL−sys by 2DST as well as the corresponding MWTA FC/EMS by 2DE increased significantly after exercise, most likely reflecting an increase in regional and global myocardial contractility.25,47,48 Overall, the results of this study suggest that 2DST derived strain and strain rate are more sensitive and more reliable than 2DE and TDI measurements for assessment of stress-induced changes in myocardial function.
Analysis of myocardial motion by 2DST provides interesting insights into the mechanics of LV contraction. The basal-to-apical gradient seen in DL−sys again emphasizes the importance of longitudinal LV function, indicating that during LV systole the apex remains relatively stationary while the atrioventricular plane moves toward the apex.46,49 The decrease in DR−sys and—except for apical segments—in DL−sys postexercise is consistent with the concurrent drop in ɛR, ɛL, SV, and EF. A partly significant, but not very distinct apical-to-basal ɛL gradient was seen at rest but not after exercise. An apical-to-basal decrease in ɛL has also been shown in humans,50–52 pigs,53 and goats,54 although in other studies strain was evenly distributed throughout the myocardium.46 Assessment of tɛL indicated that, in agreement with recently published findings in people,51 the peak ɛL occurred significantly earlier in the apex compared with mid septal and basal septal segments. This finding is likely related to the fact that in mammalian hearts, electrical activation of the ventricles begins near the apical septum and spreads rapidly toward the base.53–56 Independent of HR, the SRL−sys was highest in the apical septal segment compared with all other segments, suggesting a slight apical-to-basal SRL−sys gradient, similar to findings in pigs53 and goats.54 Conversely, studies in people did not show significant differences in SRL−sys between segments.46,52
Evaluation of regional ventricular function can provide important diagnostic and prognostic information on human patients with coronary artery disease,24,25,27 but the clinical relevance of regional wall motion analysis in horses is unknown. Therefore, there is a need to investigate novel echocardiographic methods to better quantify myocardial wall motion abnormalities that could be suggestive of occult myocardial disorders. Echocardiographic assessment of regional myocardial function has traditionally been achieved by combining visual analysis of endocardial motion with the measurement of wall thickening and thinning from 2D images.17–19 Wall motion can also be evaluated semiquantitatively by generation of a wall motion score index.19 However, these methods are largely subjective.57 The low interobserver agreement58,59 and the potential for failure to identify areas of subtle abnormalities make these methods relatively inaccurate and unreliable.
Ischemic regions are characterized by a decrease in systolic velocities,40,41,60 a decrease in systolic strain and strain rate,61,62 and a delayed onset of relaxation.63 The 2DST technology provides an objective way to identify hypokinetic and akinetic myocardial segments and to quantify the degree of wall motion anomalies.24,30,31 However, to our knowledge there are no established cut-off values to differentiate normokinetic from hypokinetic and akinetic segments. The definition we used in this study was chosen based on a human study using MRI as the gold standard for identification of hypokinesia and akinesia.33 By our definition, a relatively large number of segments were judged as being hypokinetic. All 5 horses were affected, but none of the segments was consistently judged as being hypokinetic on all 3 recordings. In our opinion, the high number of hypokinetic segments detected in this population of healthy athletic horses is likely to be a result of artifacts related to the image quality or to the tracking algorithm rather than true, clinically relevant hypokinesia. We propose that hypokinesia should only be diagnosed when the same segment is judged as being hypokinetic in all 3 recordings of the same HR and when the affected segment is the same throughout the postexercise period.
Although stress echocardiography is commonly used to detect ventricular dyssynchrony in people, there is currently no single index that is considered optimal for assessment of dyssynchrony.64 Evaluation of dyssynchrony by 2DST can be achieved by visual assessment of the graphical display of segmental myocardial motion and by calculating a variety of synchrony indices.32,65,66 In this study, we assessed synchrony based on SVA of the trace display as well as by using different percentiles of all calculated STIɛR as cut-off values.32 Although not formally tested, agreement between SVA and the more objective percentile-based method was obviously poor. Some of the recordings that were judged as dyssynchronous when using a cut-off value higher than the 75 and the 90% percentile, respectively, were judged as synchronous by SVA. Based on these results and the previously reported poor reliability of the STIɛR,32 we cannot recommend the use of the STIɛR as a single index of myocardial dyssynchrony in horses.
Further studies in a larger population including healthy horses and horses with myocardial disease will be necessary to elaborate a clinically applicable and objective definition for hypokinesia and akinesia and to investigate the best diagnostic approach to detect ventricular dyssynchrony on horses. In any case, subjective confirmation of adequate tracking by the observer and SVA of the 2DST trace display will likely remain important in the assessment of regional wall motion abnormalities in horses.
We were able to show that some of the echocardiographic indices of LV function obtained within the first 5 minutes after high-speed treadmill exercise are highly variable and largely depend on HR. Sandersen et al9 showed that most of the linear M-mode variables of LV size and function measured during stress echocardiography did not differ significantly from baseline at HR below 100 minute−1. These findings are in agreement with the results of this study in healthy horses, demonstrating that all of the potentially useful indices of LV systolic function, in particular ɛR, ɛL, SRR−sys, and SRL−sys as well as MWTA FC/EMS, Sm, and PEP/ET, showed consistent and significant increases compared with baseline at HR above 100 minute−1. Whether horses with stress-induced myocardial dysfunction show abnormalities in a wider range of HR will have to be investigated in future studies. In any case, the results suggest that the instantaneous HR needs to be considered when assessing quantitative stress echocardiographic measurements in individual horses.
The relatively small study population certainly needs to be listed as a limitation of this study, especially because values for higher HR could not be obtained in 1 horse. However, it was not possible to recruit a larger number of healthy horses in athletic condition that would have been allowed to undergo 3 consecutive exercise tests within a reasonable time frame. Nonetheless, the data still allowed identifying a number of echocardiographic indices that might prove useful for quantitative assessment of stress echocardiograms in horses.
Although the results were interpreted and discussed all together, it needs to be emphasized that the SAX 2DE recordings, the LAX 2DE recordings, and the TDI recordings were acquired on 3 separate occasions. This may be considered a 2nd limitation of the study. However, the goal of this study was to observe changes over time in a variety of echocardiographic indices postexercise and to relate the measurements to HR. In order to acquire complete datasets for each view and for each echocardiographic modality, including a minimum of 3 cardiac cycles at each target HR, it was necessary to obtain the recordings on 3 separate occasions.
Further limitations are of technical nature. Acquisition and analysis of high-quality recordings require extensive operator training as well as high-end echocardiographic equipment with digital raw-data storage and off-line postprocessing capabilities. On postexercise recordings, excessive translational motion of the heart, poor acoustic coupling, and a variety of artifacts sometimes prevent accurate identification of the myocardial border, particularly on the apex and on the septal base in the LAX plane. Generally, 2DST analysis of LAX recordings was more difficult than analyzing SAX images, and achieving adequate tracking of LAX recordings often required several attempts or was not possible (leading to exclusion of segments from further analyses), whereas tracking of SAX segments mostly was adequate at the first try. In rare cases, end-systolic tracking appeared slightly inaccurate, although the software approved the quality of the tracking. This might have been related to the rather low frame rate that was insufficient to resolve the high maximum wall motion velocities occurring at high HR in some segments. Theoretically, this phenomenon may lead to an underestimation of peak-systolic strain, strain rate, or displacement. However, because of the low number of affected segments, we do not anticipate a significant influence on the final results.
In conclusion, we were able to show that stress echocardiographic recordings can be quantitatively analyzed by conventional 2DE as well as novel 2DST methods. Volumetric estimates of SV and EF by 2DE, MWTA FC/EMS by 2DE, as well as radial and longitudinal strain and strain rate by 2DST can be useful for quantitative stress-echocardiographic assessment of global and regional LV systolic function in horses, whereas linear and most area-based 2DE indices do not allow detecting significant and consistent stress-induced changes in LV function. Pulsed-wave TDI provides little additional information and its use is limited by poor image quality and unreliable identification of velocity waves at high HR. The results of this study further indicate that quantitative echocardiographic indices of LV function must be evaluated in view of the instantaneous HR. The detection of stress-induced hypokinesia, akinesia, and dyssynchrony in diseased horses requires additional investigations.
The results of this study provide a sound basis for future investigations into the clinical value of stress echocardiography in horses. It remains to be shown in a larger study population which of the echocardiographic indices will be clinically useful for quantitative assessment of LV function during stress echocardiography in horses with cardiac disease.