DISCUSSION
This study reports the largest multicenter data collection for
development of 3D echocardiographic z-scores for LV volumes and function
in healthy North American children using the semi-automated
quantification method. The feasibility was 79% analyzable datasets at
the core laboratory. We demonstrated that the semi-automated software
quantification with LV border adjustment was more reliable between
centers than automated software quantification. Although automated
software quantification took less time, the greater variability in
measurement rendered it less reliable, and therefore the normative
Z-score values were derived from the semi-automated method.
Our study had feasibility of 79% of obtaining adequate 3D data for
analysis at the core laboratory, similar to another multicenter study in
the pediatric age group 8. Krell et al reported having
a feasibility of 74% in their multicenter study but our study
population was larger with more patients. Kuebler et al reported
normative LV volume and functional values in 238 pediatric subjects of
different age group and body surface area 9. Only 14%
of their subjects were under the age of 5 (34/238) 9.
Our study is notable in that 27% (141/523) of the subjects were under
the age of 5 and 18% were less than 3 years old. This is the population
that is technically challenging to acquire 3D volumes as young patients
are unable to hold their breath or stay relatively motionless during the
acquisition, obviating “stitch artifact”. On the other hand, they may
have the best imaging window due to smaller chest walls and ability to
incorporate the entire ventricular volume into the dataset. Cantinotti
et al studied 800 Italian healthy children and reported excellent
feasibility of 91%; however, the feasibility for smaller children with
smaller BSA less than 0.5 was 68% to 80% respectively10.
We did not find that the automated quantification software improved the
reproducibility in volume and function analysis. There was wide LOA
between automated and semiautomated LV quantification in all centers.
The automated software frequently did not track the LV endocardial
borders. This became apparent in the intraobserver reproducibility in
the core lab when the same LV datasets were re-measured using the
semi-automated contouring method. The intraobserver reproducibility was
excellent when semi-automated method was used and showed small bias and
LOA. However, the intraobserver reproducibility did not have good
agreement when automated versus semi-automated quantification comparison
was used on the same LV datasets. This study highlights the difference
between pediatric and adult studies of using automated versus
semi-automated contouring of LV volumes and function. We postulate that
the current automated contouring does not adequately track LV contours
in pediatric 3D datasets because the fully automated algorithms are
built based on adult 3D datasets. The time for semi-automated contouring
of the LV was not more than a mean of 2-3 minutes in all centers, which
should be acceptable for routine clinical use.
Our study is unique in that we performed extensive analysis of
reproducibility by comparing all 3D datasets from 4 different centers to
the core lab using the semi-automated and automated methods. The
semi-automated methods between centers were reproducible. The percent
difference in the LV EDV was ± 30% indicating that if an individual
measured the LV EDV at 10ml, the difference could be ± 3ml. This is an
acceptable range of measures between centers. The percent difference for
LV ESV measurement was also about ± 30% (Figure 3). The LOA of LV
volumes and EF were wider using the automated methods compared to the
semi-automated methods between the core lab to other centers, indicating
that LV volumes and EF were not reproducible using this method. Prior
studies from Kuebler et al and Cantinotti et al have described pediatric
normative LV volumes and function derived from single centers9,10. Similar to previous studies, LV volumes indexed
to the BSA demonstrated gradual increase from childhood to adolescent
years 8-12.
The mean absolute percent difference in 3D LV EF between all centers in
our study was 7% with the observed difference of 4.2% if the LV EF was
measured at 60%. This is better than the reported 2D LV EF absolute
percentage difference of 11.2% in the Pediatric Heart Network study13. 3D LV EF has been reported to be more accurate and
reproducible than 2D LV EF in adults and children because 3DE does not
rely on geometric assumptions and is less affected by acquisition
technique such as foreshortening 3,14-18. Thus, it is
recommended that 3D LV EF should be reported in clinical echocardiograms
in centers with experience in 3DE 18. Our study
demonstrated that the reproducibility of 3D LV EF is good to excellent
and can be used in multiple centers.