Our study provides the most comprehensive simultaneous 2D and 3D characterization of myocardial mechanics to date in patients with severe AS and preserved LVEF. These patients demonstrated subclinical LV systolic dysfunction in the form of reduced GLS and GRS along with concomitant increases in GCS, apical rotation, and peak systolic twist, which may represent compensatory mechanisms to maintain the LVEF within normal limits. We were able to demonstrate these changes in mechanics by both 2D and 3D speckle-tracking echocardiography. Furthermore, GLS showed a weak correlation with indexed LVEDV, a measure of preload, and a modest correlation with valvulo-arterial impedance, a measure of afterload.
Characterization of myocardial mechanics through the echocardiographic assessment of myocardial deformation, or strain, can provide a more thorough representation of LV contractile function (27). Through the measurement of strain, changes in LV myocardial contraction can be detected in three directions: longitudinal strain reflects contraction of the longitudinally arranged endocardial and epicardial fibers; circumferential strain represents contraction of the circumferentially arranged mid-layer fibers; and radial strain denotes contraction of the full-thickness LV wall. In the presence of subendocardial ischemia, longitudinal strain is generally the first to decrease, due to the longitudinal arrangement of endocardial fibers (28). A subsequent increase in circumferential strain can compensate for declines in longitudinal strain to maintain normal radial strain and LVEF.
Patients with severe AS and preserved LVEF in our cohort exhibited lower-than-normal GLS, a finding consistent with that found in several prior studies (5-19). In patients with severe AS, the increased afterload may lead to left ventricular hypertrophy, decreased coronary perfusion, subendocardial ischemia, and eventually myocardial fibrosis (3,4). The endocardium is usually the most vulnerable to increased wall stress and stress-induced ischemia with LV pressure overload, resulting in impairment in longitudinal strain before others (29). Indeed, layer-specific strain analysis reveals a reduction in GLS limited to the subendocardial layer even in patients with mild AS, which worsened with progression to involve the other layers with increasing severity of AS (29).
Reduced GLS was accompanied by increased GCS in our cohort of patients with severe AS and preserved LVEF, in keeping with the tendency for circumferential strain to increase in order to maintain a normal LVEF (28). However, while GLS has consistently been shown to be low in patients with severe AS, prior studies have demonstrated either a decrease (5,10,30) or an increase in GCS (10,31) in these patients. Of note, patients in those previous studies with a reduced GCS tended to have a reduced LVEF whereas those with an elevated GCS tended to have a preserved LVEF. It is possible that these patients initially develop increases in GCS to counter reductions in GLS and maintain a normal LVEF but then eventually experience reductions in GCS and as a result LVEF as well.
In addition to increases in circumferential strain, apical rotation and peak systolic twist were also significantly higher than normal in our cohort of patients with severe AS and preserved LVEF, which is consistent with prior findings (7,10,11,30,32). Prior studies have reported good correlations between LV twist derived from 2D speckle-tracking echocardiography and magnetic resonance imaging (33,34). The counter-coiled helical arrangement of subendocardial and subepicardial fibers generates an LV twist that has been proven to be fundamental to LV contraction and therefore LVEF (35,36). Similar to circumferential strain, increases in apical rotation and twist may thus also serve to compensate for the declines in GLS in order to maintain normal LVEF and cardiac output. In fact, one prior study showed that patients with lower LVEF values tended to exhibit higher degrees of apical rotation (10).
Few prior studies have assessed changes in radial strain and basal rotation in patients with severe AS (5,7,11). In our cohort, patients similarly demonstrated lower GRS (5) and no difference in basal rotation (7,11) compared with normal values. Unlike all prior studies, our study represents to our knowledge the first to characterize longitudinal, circumferential, and basal strain, along with apical rotation, basal rotation, and twist within the same cohort of patients with severe AS using both 2D and 3D speckle-tracking echocardiography.
In patients with degenerative AS, arterial compliance is frequently reduced, which contributes to increased afterload and decreased LV function. Hence, the LV is often subjected to a double afterload from valvular obstruction and from reduced systemic arterial compliance (1,2). Zva is a simple index that provides an estimate of the afterload imposed on the LV and is an important index of AS severity and predictor of LV dysfunction and outcomes (1,37-39). Zva is moderately elevated in patients with severe AS, and aortic valve replacement often only reduces the valvular component of afterload and has no effect on the arterial compliance of elderly patients, which may be due to other comorbidities, such as hypertension and atherosclerosis (39,40). Our study further demonstrated a correlation between 2D and 3D GLS and Zva but no significant relationship between Zva and other deformation parameters. GLS also correlated with increasing LVEDV and E/e’ ratio. The increase in LVEDV and Zva represents a hemodynamic load that markedly increases wall stress and results in depressed myocardial contractility (22).
Previous studies have reported conflicting results of comparisons of 2D and 3D speckle-tracking echocardiography measurements, possibly because of major differences in the study populations such as sample size and the severity of AS, as well as methodology such as software used for measurement of strain (19,41-3). One prior study showed that 3D was not superior to 2D in measuring any of the three components of LV deformation (12). Our study showed a modest agreement between 2D and 3D GLS and a poor agreement among other parameters. There was also a similar weak correlation between 2D and 3D GLS and Zva.
Theoretically, 3D imaging should be more accurate as it can overcome well-known limitations of 2D imaging by avoiding foreshortened apical views, providing a more complete picture of myocardial deformation in three dimensions, and reducing out-of-plane motion, which may affect the accuracy of LV strain and twist measurements. However, the lower temporal and spatial resolutions of 3D images are potential limitations that could adversely affect the accuracy of 3D measurements acquired at the lower frame rates (42,43). Nevertheless, our 3D measurements were still able to capture the pattern of myocardial deformation found in patients with severe AS observed on 2D, in which GLS and GRS were reduced and accompanied by an increase in GCS, apical rotation, and twist.
Our study had several limitations worth considering. First, it was a single-center observational study, which may reduce the generalizability of the results. However, the prospective design of the study allowed for more precise patient selection and more comprehensive data collection that would not have been possible with a retrospective design. Second, given the elderly cohort of patients with severe AS, we were unable to recruit similar healthy age- and sex-matched subjects for comparison. Nevertheless, we used, to our knowledge, the best available reference values that have been previously published in literature for comparison including two large meta-analyses of 2D and 3D global strain. Third, our patients had pertinent comorbidities such as coronary artery disease, which could theoretically influence myocardial deformation. However, it would not be possible to fully account for all comorbidities that could affect strain in these patients. Our cohort therefore reflects a real world population of patients with severe AS with comorbid conditions. Fourth, we did not validate the deformation measurements against reference standards such as tagged magnetic resonance imaging or sonomicrometry. Furthermore, the relatively low frame rate of real-time 3D echocardiographic imaging could potentially lead to underestimating strain values. As well, the relatively high body mass index in our cohort may have led to poor image quality. Nevertheless, the similar findings obtained on both 2D and 3D provided a degree of quality assurance. Finally, it may not be possible to extrapolate our exact measurements to other ultrasound machine systems or 3D speckle tracking software, although we suspect that the pattern of deformation abnormalities observed may still be consistent.