assessment of left ventricular ( lv ) function is the most common and clinically relevant task in the congenital echocardiography laboratory .
historically , those measurements have been estimated using m - mode ( mm ) and two - dimensional ( 2d ) echocardiography , with several limitations .
strain echocardiography , on the other hand , permits the quantification of lv global and regional function , which provides new insights in different experimental and clinical scenarios .
recently , lv strain derived from 3d speckle - tracking echocardiography ( 3d - ste ) has been validated against cardiac magnetic resonance imaging in children and adults .
this new technique has the potential to better evaluate the lv function in neonates with congenital heart disease and to be of help in the surgical decision - making .
however , to the best of our knowledge , there are no data on 3d - ste in full - term neonates to assess lv mechanics . in this study
, we sought to establish the feasibility of the acquisition and analysis of 3d data sets , and to establish using 3d - ste , normal values for lv volumes , and ejection fraction ( ef ) as well as the 3d global strain ( gs ) parameters in a group of healthy neonates .
all the subjects were born in our institution and were either awaiting the discharge of their mothers or presenting for their first newborn baby regular checkup .
the inclusion criteria were : 
 no history of congenital oracquired heart disease , andcompletely normal results on 2d and doppler echocardiography , with no structural defects and with normal chamber size and systolic function . 
 
no history of congenital or acquired heart disease , and completely normal results on 2d and doppler echocardiography , with no structural defects and with normal chamber size and systolic function .
exclusion criteria were : 
 structural congenital or acquired heart disease , abnormal cardiac rhythms , andhypertension and/or other acute or chronic illnesses . 
 
structural congenital or acquired heart disease , abnormal cardiac rhythms , and hypertension and/or other acute or chronic illnesses .
all echocardiography studies were performed by an experienced cardiac sonographer using ie 33 platform scanner ( philips medical systems , andover , ma ) .
matrix - array transducer ( s8 ) was used for the routine mm , 2d , and doppler study , and a dedicated 3d full sampling transducer ( x7 ) was used for the 3d full volume data sets acquisition .
studies were performed with the babies asleep or quite suckling on a bottle of formula ; attention was made to acquire the data sets during the resting phase of the periodic breathing or shallow breathing to minimize heart translation and the effect of breathing .
the echocardiograms were transferred to xcelera r3.3 cardiology pacs system ( philips medical systems , andover , ma ) and were analyzed offline .
the routine echo study was reported in a separate session than that of the 3d analysis . the same experienced observer , analyzed and reported the 3d study , blinded to the finding of the routine examination .
adequate 3d data sets ( without stitching artifacts and containing the whole of the lv ) were analyzed using 4d lv analysis software v3.1 , ( tomtec imaging systems ) .
the software allows a semi - automated detection of the lv border following the identification of the mitral valve annulus and lv apex by the operator [ figure 1 ] .
the others resemble the two and four chamber views of the lv , used in the biplane method of lv volumetric measurement .
in addition , following manual adjustments of the endocardial surface was performed as necessary to include the papillary muscles within the lv cavity ; the 3d endocardial surface is automatically tracked using 3d speckle - tracking technology throughout the cardiac cycle .
the software eventually provides longitudinal , circumferential , radial , and tangential time curves , from which peak gs and averaged peak strain at the basal , mid - ventricular , and apical levels are determined [ figure 2 ] .
initial step of the analysis of the three - dimensional dataset : an automated tri - plane construction of the left ventricle automated border detection , both at end diastole and systole with the resultant volume and deformation calculations principal tangential strain in 4d lv analysis describes the shortening of a surface element along the main contraction direction .
it is , thus , a measure of regional myocardial contraction ability , and may represent the vector summation in longitudinal and circumferential direction , and the resulting direction of the contraction of the muscle fibers that are aligned tangentially to the myocardial surface . in addition to track the endocardial border , the software allowed the tracking and tracing the epicardial border as well . in this way
, the system calculated the volume of the endocardial cavity and estimated myocardial mass . as a result , the volume of the lv all through the cardiac cycle was measured and the myocardial mass was calculated . to assess intraobserver variability , the same observer ( z.b . )
measured the 3d strain analysis of 10 randomly selected newborns twice at an interval of 2 months to avoid recall bias . to assess interobserver variability ,
3d strain measurements were performed by a second observer ( g.s . ) , who was blinded to the results of the first observer ( z.b . ) .
all demographic , conventional , echocardiographic and 3d strain data are presented as numbers or percentages ( mean  standard deviation ) .
linear correlation analysis was performed to assess the relationship between 3d strain variables ( global longitudinal strain [ gls ] , global circumferential strain [ gcs ] , global circumferential strain [ grs ] , global transverse strain [ gts ] , and twist and torsion ) and age , heart rate , weight , height , and 3d derived lv volumes , lv ef , lv stroke volume ( sv ) , and lv mass indexed for body surface area ( bsa ) .
multiple linear regression analysis was performed to determine the additional effect of anthropometrics ( age , heart rate , weight , and height ) and conventional echocardiographic parameters on the 3d - studied strain variables .
the anthropometric and echocardiographic parameters were considered as potential dependent variables , and all variables were simultaneously entered in the regression .
statistical analyses were performed using spss for windows version 16.0 ( spss , inc . ,
intraobserver and interobserver agreements were calculated using the coefficient of variation ( i.e. , the percentage absolute difference between the measurements divided by their mean value ) .
all demographic , conventional , echocardiographic and 3d strain data are presented as numbers or percentages ( mean  standard deviation ) .
linear correlation analysis was performed to assess the relationship between 3d strain variables ( global longitudinal strain [ gls ] , global circumferential strain [ gcs ] , global circumferential strain [ grs ] , global transverse strain [ gts ] , and twist and torsion ) and age , heart rate , weight , height , and 3d derived lv volumes , lv ef , lv stroke volume ( sv ) , and lv mass indexed for body surface area ( bsa ) .
multiple linear regression analysis was performed to determine the additional effect of anthropometrics ( age , heart rate , weight , and height ) and conventional echocardiographic parameters on the 3d - studied strain variables . the anthropometric and echocardiographic parameters were considered as potential dependent variables , and all variables were simultaneously entered in the regression .
statistical analyses were performed using spss for windows version 16.0 ( spss , inc . , chicago , il ) .
intraobserver and interobserver agreements were calculated using the coefficient of variation ( i.e. , the percentage absolute difference between the measurements divided by their mean value ) .
of the 50 healthy full - term newborns , 10 were excluded because their parents refused to give consent for this study .
two babies had more than mild shunting lesions ( atrial septal defect type ii and a large patent ductus arteriosus ) ; both were not included in our data analysis .
thus , the final study group consisted of 38 healthy newborns ( mean age was 3.7  4.7 days , range : 1 - 15 days , and gestational age of 38.1  1.1 weeks ) .
mean weight and bsa were 3.1  0.5 kg and 0.19  0.02 m , respectively .
general characteristics of the studied sample bsa = body surface area , hr = heart rate conventional echocardiographic parameters and 3d lv global myocardial strain variables of the studied subjects are presented in table 2 .
measured echocardiographic parameters of the studied sample 3d lv edv = three - dimensional left ventricular end diastolic volume , 3d lv esv = three - dimensional left ventricle end systolic volume , 3d lv ef = threedimensional left ventricular ejection fraction , 3d lv sv = three - dimensional left ventricular stroke volume , 3d gls = three - dimensional global longitudinal strain , 3d gcs = three - dimensional global circumferential strain , 3d grs = threedimensional global circumferential strain , 3d gts = three - dimensional global transverse strain linear regression analysis was performed to assess the relationship among 3d strain variables , age , weight , lv volumes , lv mass lv sv , and lv ef .
gcs was significantly correlated with age ( r = 0.41 , p = 0.01 ) , sv ( r = 0.55 , p = 0.0003 ) , lv mass index ( r = 0.36 , p = 0.027 ) , and ef ( r = 0.90 , p < 0.0001 ) .
grs was significantly correlated with age ( r = 0.43 , p < 0.0001 ) and ef ( r = 0.79 , p < 0.0001 ) , while gts was significantly correlated only with ef ( r = 0.61 , p = 0.0002 ) .
multiple linear regression analyses among the anthropometric and standard echocardiographic parameters were performed to determine the independent effect of these parameters on the 3d gs variables .
only age was significantly associated with gls ( p = 0.046 , r = 0.20 ) , while gcs ( p < 0.0001 , r = 0.90 ) , grs ( p < 0.0001 , r = 0.79 ) , and gts ( p = 0.003 , r = 0.61 ) were significantly associated only with ef .
the coefficient of variation was very good for gls ( intraobserver 0.09% and interobserver 1% ) and gcs ( intraobserver 2.5% and interobserver 2.8% ) , but poor for grs and gts ( intraobserver 10% and interobserver 15% ) .
the coefficient of variation was very good for gls ( intraobserver 0.09% and interobserver 1% ) and gcs ( intraobserver 2.5% and interobserver 2.8% ) , but poor for grs and gts ( intraobserver 10% and interobserver 15% ) .
our data show that 3d - ste analysis is feasible on the consecutive healthy newborns , and we presented reference data for this population .
the most recent ase\eacvi guidelines consider ste - derived gls as reproducible and feasible for clinical use offering incremental prognostic data over lv ef in a variety of cardiac conditions .
thus , gls may become a sensitive tool to assess lv mechanics and function in newborns with various congenital heart diseases .
unfortunately , only few data are available in the pediatric and newborn population on ste - derived strain variables and 3d - ste data are available only for preterm ones [ table 3 ] .
however , differences in gls values across different studies also reflect the use of different machines , software , and different algorithms .
comparison with previous studies na = not available , 2d = two - dimensional , 3d = three - dimensional , cpa = cardiac performance analysis in agreement with the previous studies , gls is a very reproducible parameter and this could facilitate its routine clinical application .
only a very weak association ( r = 0.20 ) between age and gls was demonstrated . while at multivariate analysis , gcs , gts , and grs were significantly associated only with 3d lv ef .
this finding is consistent with the previous observations that lv size and mass continue to grow from birth to puberty but that lv systolic function , as shown by lv ef and now by strain variables , is relatively consistent from infancy . in this regard
, the use of normative values for 3d - derived gls will be greatly facilitated by its substantial independence of anthropometric , echocardiographic , and demographic factors that constitute confounding effects in other techniques .
the determination of reproducibility of 3d lv strain and torsion measurements is also important when applying this new technology to daily clinical practice .
inter and intraobserver variability of 3d gls and gcs was very good , suggesting these parameters are ready for the clinical use .
on the other hand , reproducibility of gts , grs twist , and torsion is still high , underscoring the need for more technical advancement before is ready for clinical practice .
there is a learning curve for operators new to the technique to optimize imaging for the entire endocardial wall throughout the cardiac cycle and provide reproducible point selection for tracing .
fundamental limitations of ultrasound , such as reverberation , shadowing , dropouts , chamber foreshortening , and movement artifacts , can limit feasibility . in children and newborns ,
most of these limitations are overcome because of the usual , very good image quality as confirmed by our findings and previous studies on infants or children with over 90% feasibility .
the relatively low frame rate of rt3de imaging compared with a high heart rate could potentially lead during the analysis to underestimating strain values .
because of this limitation , strain rate and lv twisting and untwisting velocities can not be examined .
our radial strain values are significantly lower than in other studies , this may be due to different algorithms and formulas , which are proprietary and hidden from end users , and probably because in previous studies , radial strain calculations were derived from the endocardium .
it should be noted that the published literature has suggested that there is variability in lv volume , mass , and function among certain ethnic groups .
the determination of reproducibility of 3d lv strain and torsion measurements is also important when applying this new technology to daily clinical practice .
inter and intraobserver variability of 3d gls and gcs was very good , suggesting these parameters are ready for the clinical use .
on the other hand , reproducibility of gts , grs twist , and torsion is still high , underscoring the need for more technical advancement before is ready for clinical practice .
there is a learning curve for operators new to the technique to optimize imaging for the entire endocardial wall throughout the cardiac cycle and provide reproducible point selection for tracing .
fundamental limitations of ultrasound , such as reverberation , shadowing , dropouts , chamber foreshortening , and movement artifacts , can limit feasibility . in children and newborns ,
most of these limitations are overcome because of the usual , very good image quality as confirmed by our findings and previous studies on infants or children with over 90% feasibility .
the relatively low frame rate of rt3de imaging compared with a high heart rate could potentially lead during the analysis to underestimating strain values .
because of this limitation , strain rate and lv twisting and untwisting velocities can not be examined .
our radial strain values are significantly lower than in other studies , this may be due to different algorithms and formulas , which are proprietary and hidden from end users , and probably because in previous studies , radial strain calculations were derived from the endocardium .
it should be noted that the published literature has suggested that there is variability in lv volume , mass , and function among certain ethnic groups .
3d gls analysis using the new 3d - ste is feasible and reproducible in the newborns .
further investigation is warranted for potential clinical application of this new technology in a pediatric population .
 aims : three - dimensional speckle - tracking echocardiography ( 3d - ste ) is a promising new technique to evaluate left ventricular ( lv ) mechanics . the feasibility and normal values of lv strain using 3d - ste 
 have recently been established in adults and children . 
 unfortunately , no data are available in neonates . 
 the aims of this study were to evaluate the feasibility and establish normal values of 3d lv volumes , ejection fraction ( ef ) , and the 4 normal strains in healthy neonates.materials and methods : of 50 consecutive newborns who were delivered at our hospital or returned to their first newborn follow - up within the first 3 weeks of life , 38 babies underwent full echocardiographic evaluation , including the acquisition of at least 3 full volume data sets from the apical window , while naturally sleeping . 
 data sets were analyzed offline . 
 global lv longitudinal , circumferential , and radial strain , as well as 3d lv volumes and ef , were measured using 3d-ste.results:of the 50 newborns , 2 patients were excluded because of significant intra - cardiac shunts , and in another 10 subjects , parents did not give consent . 
 at least one data set was adequate for analysis in all the remaining subjects . 
 mean indexed lv diastolic , systolic volumes , and ef were 24.7  3.6 ml / m2 , 9.2  1.3 ml / m2 , and 63%  3.7% , respectively . 
 normal global longitudinal , circumferential , radial , and tangential 4d strain were 20.9%  2.8% , 32.4%  3.1% , 44.3%  3.4% , and 39.7%  3.4% , respectively.conclusions:3d-ste is feasible in newborns without the needed for sedation . 
 reference values of normal , regional , and global lv 4d strain and volumes were obtained . 
INTRODUCTION
MATERIALS AND METHODS
Statistical analysis
RESULTS
Intraobserver and interobserver variability
DISCUSSION
Reproducibility
Limitations
CONCLUSIONS
Financial support and sponsorship
Conflicts of interest