Background Right ventricular (RV) systolic function is an important prognostic determinant of cardiopulmonary pathologies in premature infants. Measurements of dominant RV longitudinal deformation are likely to provide a sensitive measure of RV function. An approach for image acquisition and post-acquisition processing is needed for reliable and reproducible measurements of myocardial deformation by two-dimensional speckle-tracking echocardiographic (2DSTE). The aim of this study was to determine the feasibility and reproducibility of 2DSTE measurement of RV peak global longitudinal strain (pGLS) and systolic strain rate (pGLSr) in premature infants, and establish methods for acquiring and analyzing strain Methods We designed the study in two phases: (i) a Training Phase to develop methods of image acquisition and post-processing in a cohort of 30 premature infants (born at 28 ± 1 weeks), and (ii) a Study Phase to prospectively test in a separate cohort of 50 premature infants (born at 27 ± 1 weeks) if the methods improved the feasibility and reproducibility of RV pGLS and pGLSr measurements to a clinically significant level assessed by Bland Altman analysis (bias, limits of agreement (LOA), coefficient of variation (CV), and intra-class correlation (ICC). Results Strain imaging was feasible from 84% of the acquisitions using the methods developed for optimal speckle brightness and frame rate for RV-focused image acquisition. There was high intra-observer (bias 3%, 95% LOA −1.6 to +1.6; CV 2.7%; ICC 0.97, p=0.02) and inter-observer (bias 7%, 95% LOA −4.8 to +4.73; CV 3.9%; ICC 0.93; p<0.05) reproducibility, with excellent linear correlation between the two pGLS measurements (r=0.97, p<0.01 and r=0.93, p<0.05, respectively). Conclusion This study demonstrates high clinical feasibility and reproducibility of RV pGLS and RV pGLSr measurements by 2DSTE in premature infants and offers methods for image acquisition and data analysis for systolic strain imaging that can provide a reliable assessment of global RV function.

Background Right Ventricle fractional area of change (RV FAC) is a quantitative two- dimensional echocardiographic measurement of RV function. RV FAC expresses the percentage change in the RV chamber area between end-diastole (RVEDA) to end-systole (RVESA). The objectives of this study were to determine the maturational (age- and weight- related) changes of RV FAC and RV areas and to establish reference values in healthy preterm and term neonates. Methods A prospective longitudinal study was conducted in 115 preterm infants (23-28 weeks gestational age at birth, 500-1500 gram). RV FAC was measured at 24 hours of age, 72 hours of age, 32 weeks and 36 weeks postmenstrual age (PMA). The maturational patterns of RVEDA, RVESA, and RV FAC were compared to 60 healthy full term infants in a cross sectional study (> 37 weeks, 3.5 +/− 1 kg), who received echocardiograms at birth (n=25) and one month of age (n=35). RVEDA and RVESA were traced in the RV focused apical 4-chamber view, and FAC was calculated using the formula: 100 * [(RVEDA – RVESA)/RVEDA)]. Premature infants that developed chronic lung disease or had a clinically and hemodynamically significant PDA were excluded (n=55) from the reference values. Intra- and inter- observer reproducibility analysis was performed. Results RV FAC ranged from 26% at birth to 35% by 36 weeks PMA in preterm infants (n=60) and increased almost two times faster in the first month of age as compared to healthy term infants (n=60). Similarly, RVEDA and RVESA increased throughout maturation in both term and preterm infants. RV FAC and RV areas correlated with weight (r=0.81, p<0.001), but were independent of gestational age at birth (r=0.3, p=0.45). RVEDA and RVESA correlated with PMA in weeks (r=0.81, p<0.001). RV FAC trended lower in preterm infants with bronchopulmonary dysplasia (p=0.04), but did not correlate to size of PDA (p=0.56). There was no difference in RV FAC based on gender or need for mechanical ventilation. Conclusions This study establishes reference values of RV areas (RVEDA and RVESA) and RV fractional area of change (RV FAC) in healthy term and preterm infants and tracks their maturational changes during postnatal development. These measures increase from birth to 36 weeks PMA, and this is reflective of the postnatal cardiac growth as a contributor to the maturation of cardiac function These measures are also linearly associated with increasing weight throughout maturation. This study suggests that two-dimensional RV FAC can be used as a complementary modality to assess global RV systolic function in neonates and facilitates its incorporation into clinical pediatric and neonatal guidelines.

Objective To determine the association among nonalcoholic fatty liver disease (NAFLD), metabolic function, and cardiac function in obese adolescents. Study design Intrahepatic triglyceride (IHTG) content (magnetic resonance spectroscopy), insulin sensitivity and β-cell function (5-hour oral glucose tolerance test with mathematical modeling), and left ventricular (LV) function (speckle tracking echocardiography) were determined in three groups of age, sex, and Tanner matched adolescents: 1) lean (n=14, BMI=20±2 kg/m2); 2) obese with normal (2.5%) IHTG content (n=15, BMI=35±3 kg/m2); and 3) obese with increased (8.7%) IHTG content (n=15, BMI=37±6 kg/m2). Results The disposition index (β-cell function) and insulin sensitivity index (ISI) were ~45% and ~70% lower, respectively, and whole body insulin resistance (HOMA-IR) was ~60% greater, in obese than in lean subjects, and ~30% and ~50% lower and ~150% greater, respectively, in obese subjects with NAFLD than those without NAFLD (P <0.05 for all). LV global longitudinal systolic strain and early diastolic strain rates were significantly decreased in obese than in lean subjects, and in obese subjects with NAFLD than those without NAFLD (P <0.05 for all), and were independently associated with HOMA-IR (β = 0.634). IHTG content was the only significant independent determinant of ISI (β = −0.770), disposition index (β = −0.651), and HOMA-IR (β = 0.738). Conclusions These findings demonstrate that the presence of NAFLD in otherwise asymptomatic obese adolescents is an early marker of cardiac dysfunction.

BACKGROUND: Frame rate (FR) of image acquisition is an important determinant of the reliability of 2-dimensional speckle tracking echocardiography (2DSTE)-derived myocardial strain. Premature infants have relatively high heart rates (HR). The aim was to analyze the effects of varying FR on the reproducibility of 2DSTE-derived right ventricle (RV) and left ventricle (LV) longitudinal strain (LS) and strain rate (LSR) in premature infants. METHODS: RV and LV LS and LSR were measured by 2DSTE in the apical 4-chamber view in 20 premature infants (26 ± 1 weeks) with HR 163 ± 13 bpm. For each subject, 4 sets of cine-loops were acquired at FR of <90, 90-110, 110-130, and >130 frames/s. Two observers measured LS and LSR. Inter- and intra-observer reproducibility was assessed using Bland Altman analysis, coefficient of variation, and linear regression. RESULTS: Intra-observer reproducibility for RV and LV LS was higher at FR >110 frames/s, and optimum at FR >130 frames/s. The highest inter-observer reproducibility for RV and LV LS were at FR >130 and > 110 frames/s, respectively. The highest reproducibility for RV and LV systolic and early diastolic LSR was at FR > 110 frames/s. FR/HR ratio >0.7 frames/s/bpm yielded optimum reproducibility for RV and LV deformation imaging. CONCLUSIONS: The reliability of 2DSTE-derived RV and LV deformation imaging in premature infants is affected by the FR of image acquisition. Reproducibility is most robust when cine-loops are obtained with FR/HR ratio between 0.7 – 0.9 frames/s/bpm, which likely results from optimal myocardial speckle tracking and mechanical event timing.

Background Doppler echocardiography (DE) is widely used as a surrogate for right heart catheterization (RHC), the gold standard, to assess and monitor elevated right heart pressure in children. However, its accuracy has not been prospectively validated in children. The objective of this study was to evaluate the accuracy of DE in predicting simultaneously measured RV pressure by RHC in pediatric patients, and to determine if the degree of RV hypertension affects the accuracy of DE in assessing right heart pressure. Methods Eighty children (age 0–17.9 years, median 5.5 years) with two-ventricle physiology and a wide range of right heart pressures underwent simultaneous DE and RHC. The pressure gradient between the right ventricle and right atrium was directly measured by RHC and simultaneously estimated by DE using tricuspid valve regurgitation. Patients were then grouped based on RHC measured right ventricular systolic pressure (RVSP): group 1 (n=43) with RVSP <1/2 systemic systolic blood pressure (SBP); group 2 (n=37) with RVSP ≥1/2 SBP; group 3 (n=56) with RVSP <2/3 SBP; and group 4 (n=24) with RVSP ≥2/3 SBP. Correlation and Bland-Altman analyses were performed on all groups. Accuracy was predefined as 95% limits of agreement within ±10mmHg. Results Despite a reasonable correlation between DE and RHC in all groups, there was poor agreement between techniques as RVSP/SBP increased. DE was inaccurate in 1/43 (2%) patients in group 1 versus 9/37 (24%) in group 2, and was inaccurate in 1/56 (2%) in group 3 versus 8/24 (33%) in group 4. Over- and underestimation occurred equally in all groups. Conclusion DE inaccurately estimates right ventricular pressure in children with elevated right heart pressure. It should not be relied upon as the sole method of assessing right heart hemodynamics in children with RV hypertension.

Objectives To test our hypothesis that obese adolescents have left ventricular (LV) dysfunction and remodeling that are associated with markers of cardiovascular risk and insulin resistance (IR). Study design In a cross-sectional study of 44 obese and 14 lean age-, sex-, Tanner stage-, and race-matched adolescents, IR, markers of cardiovascular risks, conventional and 2-dimensional speckle tracking echocardiography (2DSTE) measures of LV function and structure were evaluated and compared. Results The obese adolescents had significantly increased body mass index (BMI) Z-score, systolic blood pressure, fasting insulin, IR, and atherogenic lipids compared with the lean adolescents. A subgroup of obese adolescents had LV remodeling characterized by significantly increased LV mass index (LVMI, g/m2.7) and relative wall thickness (RWT). Almost all obese adolescents had LV dysfunction with peak LV global longitudinal strain (GLS,%), systolic global GLS rate (GLSR, %/s) and early diastolic GLSR significantly lower than in lean adolescents and in the normal pediatric population. BMI Z-score predicted LV remodeling [LVMI (R2= 0.34) and RWT (R2 0.10], and peak LV GLS (R2 0.15), and along with systolic blood pressure, predicted systolic GLSR (R2 0.16); (P ≤ 0.01 for all). Fasting insulin predicted early diastolic GLSR (R2 0.17, P ≤ 0.01). Conclusions Obese adolescents have subclinical ventricular dysfunction associated with the severity of obesity, increased systolic blood pressure, and IR. Ventricular remodeling is present in a subgroup of obese adolescents in association with the severity of obesity. These findings suggest that obesity may have an early impact on the cardiovascular health of obese adolescents.

Background: Pre-mature birth impacts left ventricular development, predisposing this population to long-term cardiovascular risk. The aims of this study were to investigate maturational changes in rotational properties from the neonatal period through 1 year of age and to discern the impact of cardiopulmonary complications of pre-maturity on these measures. Methods: Pre-term infants (<29 weeks at birth, n = 117) were prospectively enrolled and followed to 1-year corrected age. Left ventricular basal and apical rotation, twist, and torsion were measured by two-dimensional speckle-tracking echocardiography and analysed at 32 and 36 weeks post-menstrual age and 1-year corrected age. A mixed random effects model with repeated measures analysis was used to compare rotational mechanics over time. Torsion was compared in infants with and without complications of cardiopulmonary diseases of pre-maturity, specifically bronchopulmonary dysplasia, pulmonary hypertension, and patent ductus arteriosus. Results: Torsion decreased from 32 weeks post-menstrual age to 1-year corrected age in all pre-term infants (p < 0.001). The decline from 32 to 36 weeks post-menstrual age was more pronounced in infants with cardiopulmonary complications, but was similar to healthy pre-term infants from 36 weeks post-menstrual age to 1-year corrected age. The decline was due to directional and magnitude changes in apical rotation over time (p < 0.05). Conclusion: This study tracks maturational patterns of rotational mechanics in pre-term infants and reveals torsion declines from the neonatal period through 1 year. Cardiopulmonary diseases of pre-maturity may negatively impact rotational mechanics during the neonatal period, but the myocardium recovers by 1-year corrected age.

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