We present feasibility, reproducibility and accuracy of a novel echocardiographic method and various widely recognized echocardiographic methods for LVM-quantification. We found the following,
(1) The novelmethod has high feasibility and better intra/inter-examiner reproducibility than the other methods.
(2) Accuracy of the novel method is similar to 3DE and greater across all four defined LV geometries than 3DE-, 2DE-, and especially 1DE-methods.
(3) The novel method is simple, does not require specific training, and provides a reliable alternative or supplement to LVM-quantification
(4) Since the biplane model is already a standard procedure commonly utilised for echocardiography, this novel method should not cause any considerable delay. The formula can easily be integrated in any echocardiographic analysis software for automatic quantification and has the potential to provide a useful tool in busy echocardiography labs.
Pitfalls of applying linear measurements
It is unsurprising that the cube formula has been the most common method for LVM-quantification since the 1970’s, as this method is simple, feasible and useful in large population studies[1–3]. However, its simplicity makes it susceptible to measurement errors that make it less suitable for individual and serial measurements. For instance, recording a LVID of 45 mm with a small wall thickness measurement error of 11 mm instead of 10 mm yields 14% increase in LVM. Whereas wall thickness recordings using the novel method are derived from the whole circumferential area, and less sensitive to minor measurement errors. This vulnerability of methods deploying linear measurements to small differences that impact LVM measurement is reflected in the increased day-to-day- and intra-/inter-examiner variations for DEV compared to the novel method (Table 3). High variations indicate decreased reproducibility and less ability to identify small yet significant real differences. Compared to the conventional method using DEV, our novel method presents lower variations and is thereby much more suited for monitoring serial measurements and comparing measurements by different examiners. Figure 6 demonstrates three patients with excellent image quality where methods deploying linear measurements fail to accurately quantify LVM: Example A has hypertrophic cardiomyopathy (HCM) and asymmetry, focal septal hypertrophy results in overestimation of t and consequently overestimation of LVM by 100g. Whilst no echocardiographic method is ideal in focal/asymmetric HCM, 2DE/3DE correlate substantially better with CMR compared to 1DE. Example B has normal geometry with normal LVM and EDVENDO. However, the LV is short (78 mm), predisposing to overestimation of the LV length and consequently LVM by 44g. Other methods overcome this pitfall and correlate better with CMR. Example C has severe aortic regurgitation, the LV is both dilated and hypertrophied. Small measurement errors are particularly magnified amongst patients with large LVs, resulting in both overestimation and large variations (315-405g) despite very small, almost visually undetectable measured differences. This is also illustrated in Figure 5 where this patient group (dilatation and hypertrophy) has large SDs, particularly amongst the method utilising linear measurements. Variations in LV geometry and size are common in cardiac disease, a cohort that particularly requires correct LVM-quantification, warranting exploration of improved methodologies.
Advantages and disadvantages with the novel method
The novel method is based on adding the mean wall thickness from a single SAX-recording to the conventional biplane tracings of the endocardium in the apical 4CH- and 2CH-view. The biplane model is traditionally applied for 2DE-quantification of volumes and function and better at correcting shape distortions compared to 1D-volume by Teichholtz or 2D-volume by A-L. The biplane model can also be used for LVM-quantification, previous studies [7, 19–24] only report endo- and epicardial border delineation (Figure 3C), not quantification (Figure 3B). It is our experience that, the epicardium is more difficult to delineate than the endocardium. We envisaged advantages in measuring the myocardial thickness in another representative view and adding it to the EDVENDO to build up the EDVEPI. This novel methodology preserves geometric variations from the biplane model and accounts for them during measurement. Compared to the BP-method, the novel method showed better feasibility, reproducibility and agreement to CMR. Several factors contribute to this observation: 1) reduced lateral resolution along the LV-walls impairs epicardial delineation in the apical views, 2) epicardial dropout, 3) echogenic pericardium, 4) small rotational errors causing the right ventricular wall to interfere with the epicardium of the inferior LV wall in the 2CH-view. It is important to remain mindful of disadvantages using the novel method, shape distortions beyond the 4CH/2CH-views are not accounted for and, inherent to 2DE-methods, inaccurate apical images and LV-foreshortening may underestimate the EDVENDO and LVM. Similar to the DEV, A-L and TE, the novel method is based on wall thickness estimation from a single imaging plane. Patients with distal wall thinning or basal septal hypertrophy are at risk of LVM-overestimation, conversely patients with focal hypertrophy are at risk of LVM-underestimation. Several cross sectional levels, at both base and apex may be considered with manifestly asymmetric geometry, although this may affect the feasibility and simplicity of the novel method.
Mean wall thickness
We recommend acquiring t using 2DE tracings in SAX (Figure 1, right panel), where it is easier to ensure centred/aligned measurements. Alignment errors in PLAX such as eccentric alignment to the long-axis will yield falsely increased anterior and posterior wall thickness. In SAX, over- or under-rotation or lateral placement of the probe may also yield a falsely increased wall thickness, but not to the same extent, since the whole circumferential traced area is included and errors induced in some segments are countered by unchanged wall thickness in other segments. Initially we compared both 1DE (linear measurements, PLAX) and 2DE (tracings, SAX) at three LV levels, mitral, chordae, mid-papillary (Figure S1 Supplementary data). 2DE at chordae level performed slightly better (Table S3 Supplementary data). Current guidelines encourage 1DE-measurements at the mitral valve leaflet tip in PLAX and 2DE-tracings at the mid-papillary level in SAX. However, results from Chetrit M. et al, Guzzetti E et al and our findings suggest that the measurement level corresponding to the mitral valve leaflet tip provides inaccurate quantification of LVM and that the preferred level is located more towards the mid-ventricular level.
Accuracy of the novel method
We evaluated accuracy according to agreement with CMR. As envisaged, methods based on 2DE/3DE demonstrate better accuracy than 1DE. The novel method seems more accurate than other 1DE/2DE-methods, demonstrates high sensitivity and specificity for hypertrophy (Table 5) and, moreover, performs best regardless of LV geometry (Figure 5). BA plots (Figure 4B) also reveal equal distribution and limited proportional bias, based on the regression line. The 3DE-agreement to CMR is consistent with recent studies, however, we observed underestimation of LVM by 30g among subjects with hypertrophy (Figure 5), mostly HCM. Only 62% of the patients with geometry profiles of “hypertrophy” were correctly classified as being hypertrophic by 3DE (Table S9 Supplementary data). This is similar to Chang et al, who also report underestimation of 20g and similar LOA in HCM, probably secondary to interpolation of small segments of the epicardium in the apex. Because of their larger LVs, the group with both hypertrophy and dilatation should also be prone to potential errors caused by interpolation of the epicardium in the apex, but we didn’t observe the same pattern in this group. A plausible explanation for our findings may be slight overestimation of LVM by CMR in subjects with HCM and small/normal EDV. It may be hard to distinguish between trabeculae and LV cavity, delineation is easier among hypertrophied patients with increased EDV. Recognised difficulties in LVM-quantification amongst HCM are illustrated by relatively large LOAs’ when comparing 3DE to CMR[28, 29].
Future aspects regarding implementation of the novel method
Our aim is to improve and facilitate echocardiographic LVM-quantification by developing a method that is simple, reproducible, accurate and reliable for monitoring individuals using serial measurements, without impairing workflow. The novel method does not require specific training and has substantially less post-processing analysis time than 3DE (Table S8, Supplementary data). Time-efficacy may be even further improved by applying simultaneous bi-plane acquisition, which most vendors provide already. Any new method needs to be both reproducible and accurate compared to the reference method. For example, a method that always quantifies the LVM to 150 g is very reproducible but inaccurate and not able to detect differences. A method with high accuracy is not useful if reproducibility is poor when serial measurements are needed. The novel method performed better than conventional 1DE-methods on all parameters and was superior to 3DE in terms of reproducibility. Once integrated with the echocardiographic analysis software, an automated and accurate LVM, comparable to 3DE/CMR and with high reproducibility will be provided. Thus, it will increase reliability of quantified LVM, improve the ability to detect real differences in LVM, and facilitate clinical decisions. It potentially provides a useful tool in busy echocardiographic labs to enhance clinical management. The novel method is not yet validated according to normal LVM-range or outcome. We recognise our report may pose challenges to interpreting established data that relied on less reproducible methodologies, although this is not unique to our observations/ findings, future data is usually developed after adopting newer technologies and methods following a period of transition. We await validated normal LVM-ranges for both the 2DE/3DE-methods and hopefully, in time also for the novel method. We also recognize that there may be uncertainty regarding conventional geometrical classification according to relative wall thickness (RWT) and LVM index. Many clinical guidelines today are based upon linear measurements in PLAX. However, these measurements may also be ascertained by converting area to diameter using SAX-tracings. Theoretically, this may be a more accurate way of achieving RWT, since all segments of the LV are represented, not only the anterior-posterior segments.
We presumed that CMR represents the true LVM and propose comparison to other modalities. Developing and testing the model on the same population, may have biased the results. Although all measurements were performed blinded, we were not blinded to the purpose of the study, which may have affected the results. Also, the limited cohort size may have obscured potential trending in the BA plots. A validation cohort may have increased the strength of this study. Further and larger studies with various vendors or machines, contrast echocardiography, with/without contrast and with greater subject heterogeneity (including ages, obesity, LV shapes, hypertrophy and cardiac disorders) would provide corroboration, and widen interpretation and applicability of the findings. We encourage and await further validation on other populations.