Establishment of the range of reference values and associated variations of two-dimensional speckle-tracking echocardiography (2DSTE)-derived left ventricular (LV) strain is a prerequisite for its ...routine clinical adoption in pediatrics. The aims of this study were to perform a meta-analysis of normal ranges of LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) measurements derived by 2DSTE in children and to identify confounding factors that may contribute to variance in reported measures.
A systematic review was launched in MEDLINE, Embase, Scopus, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library. Search hedges were created to cover the concepts of pediatrics, STE, and left-heart ventricle. Two investigators independently identified and included studies if they reported 2DSTE-derived LV GLS, GCS, or GRS. The weighted mean was estimated by using random effects models with 95% CIs, heterogeneity was assessed using the Cochran Q statistic and the inconsistency index (I(2)), and publication bias was evaluated using the Egger test. Effects of demographic (age), clinical, and vendor variables were assessed in a metaregression.
The search identified 2,325 children from 43 data sets. The reported normal mean values of GLS among the studies varied from -16.7% to -23.6% (mean, -20.2%; 95% CI, -19.5% to -20.8%), GCS varied from -12.9% to -31.4% (mean, -22.3%; 95% CI, -19.9% to -24.6%), and GRS varied from 33.9% to 54.5% (mean, 45.2%; 95% CI, 38.3% to 51.7%). Twenty-six studies reported longitudinal strain only from the apical four-chamber view, with a mean of -20.4% (95% CI, -19.8% to -21.7%). Twenty-three studies reported circumferential strain (mean, -20.3%; 95% CI, -19.4% to -21.2%) and radial strain (mean, 46.7%; 95% CI, 42.3% to 51.1%) from the short-axis view at the midventricular level. A significant apex-to-base segmental longitudinal strain gradient (P < .01) was observed in the LV free wall. There was significant between-study heterogeneity and inconsistency (I(2) > 94% and P < .001 for each strain measure), which was not explained by age, gender, body surface area, blood pressure, heart rate, frame rate, frame rate/heart rate ratio, tissue-tracking methodology, location of reported strain value along the strain curve, ultrasound equipment, or software. The metaregression showed that these effects were not significant determinants of variations among normal ranges of strain values. There was no evidence of publication bias (P = .40).
This study defines reference values of 2DSTE-derived LV strain in children on the basis of a meta-analysis. In healthy children, mean LV GLS was -20.2% (95% CI, -19.5% to -20.8%), mean GCS was -22.3% (95% CI, -19.9% to -24.6%), and mean GRS was 45.2% (95% CI, 38.3% to 51.7%). LV segmental longitudinal strain has a stable apex-to-base gradient that is preserved throughout maturation. Although variations among different reference ranges in this meta-analysis were not dependent on differences in demographic, clinical, or vendor parameters, age- and vendor-specific referenced ranges were established as well.
Pulmonary artery acceleration time (PAAT) is a noninvasive method to assess pulmonary hemodynamics, but it lacks validity in children. The aim of this study was to evaluate the accuracy of Doppler ...echocardiography-derived PAAT in predicting right heart catheterization (RHC)-derived pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), and compliance in children.
Prospectively acquired and retrospectively measured Doppler echocardiography-derived PAAT and RHC-derived systolic PAP, mean PAP (mPAP), indexed PVR (PVRi), and compliance were compared using regression analysis in a derivation cohort of 75 children (median age, 5.3 years; interquartile range, 1.3-12.6 years) with wide ranges of pulmonary hemodynamics. To account for heart rate variability, PAAT was adjusted for right ventricular ejection time and corrected by the RR interval. Regression equations incorporating PAAT and PAAT/right ventricular ejection time from the derivation cohort were then evaluated for the accuracy of their predictive values for invasive pulmonary hemodynamics in a validation cohort of 50 age- and weight-matched children with elevated PAP and PVR.
There were significant inverse correlations between PAAT and RHC-derived mPAP (r = -0.82) and PVRi (r = -0.78) and a direct correlation (r = 0.78) between PAAT and pulmonary compliance in the derivation cohort. For detection of pulmonary hypertension (PRVi > 3 Wood units · m
and mPAP > 25 mm Hg), PAAT < 90 msec and PAAT/right ventricular ejection time < 0.31 resulted in sensitivity of 97% and specificity of 95%. In the derivation cohort, the regression equations relating PAAT with mPAP and PVRi were mPAP = 48 - 0.28 × PAAT and PVRi = 9 - 0.07 × PAAT. These PAAT-integrated equations predicted RHC-measured pulmonary hemodynamics in the validation cohort with good correlations (r = 0.88 and r = 0.83, respectively), small biases (<10%), and minimal coefficients of variation (<8%).
PAAT inversely correlates with RHC-measured pulmonary hemodynamics and directly correlates with pulmonary arterial compliance in children. The study established PAAT-based regression equations in children to accurately predict RHC-derived PAP and PVR.
Establishment of the range of normal values and associated variations of two-dimensional (2D) speckle-tracking echocardiography (STE)-derived right ventricular (RV) strain is a prerequisite for its ...routine clinical application in children. The objectives of this study were to perform a meta-analysis of normal ranges of RV longitudinal strain measurements derived by 2D STE in children and to identify confounders that may contribute to differences in reported measures.
A systematic review was conducted in PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Search hedges were created to cover the concepts of pediatrics, STE, and the right heart ventricle. Two investigators independently identified and included studies if they reported the 2D STE-derived RV strain measure RV peak global longitudinal strain, peak global longitudinal systolic strain rate, peak global longitudinal early diastolic strain rate, peak global longitudinal late diastolic strain rate, or segmental longitudinal strain at the apical, middle, and basal ventricular levels in healthy children. Quality and reporting of the studies were assessed. The weighted mean was estimated using random effects with 95% confidence intervals (CIs), heterogeneity was assessed using Cochran's Q statistic and the inconsistency index (I(2)), and publication bias was evaluated using funnel plots and Egger's test. Effects of demographic, clinical, equipment, and software variables were assessed in a metaregression.
The search identified 226 children from 10 studies. The reported normal mean values of peak global longitudinal strain among the studies varied from -20.80% to -34.10% (mean, -29.03%; 95% CI, -31.52% to -26.54%), peak global longitudinal systolic strain rate varied from -1.30 to -2.40 sec(-1) (mean, -1.88 sec(-1); 95% CI, -2.10 to -1.59 sec(-1)), peak global longitudinal early diastolic strain rate ranged from 1.7 to 2.69 sec(-1) (mean, 2.34 sec(-1); 95% CI, 2.00 to 2.67 sec(-1)), and peak global longitudinal late diastolic strain rate ranged from 1.00 to 1.30 sec(-1) (mean, 1.18 sec(-1); 95% CI, 1.04 to 1.33 sec(-1)). A significant base-to-apex segmental strain gradient (P < .05) was observed in the RV free wall. There was significant between-study heterogeneity and inconsistency (I(2) > 88% and P < .01 for each strain measure), which was not explained by age, gender, body surface area, heart rate, frame rate, tissue-tracking methodology, equipment, or software. The metaregression showed that these effects were not significant determinants of variations among normal ranges of strain values. There was no evidence of publication bias (P = .59).
This study is the first to define normal values of 2D STE-derived RV strain in children on the basis of a meta-analysis. The normal mean value in children for RV global strain is -29.03% (95% CI, -31.52% to -26.54%). The normal mean value for RV global systolic strain rate is -1.88 sec(-1) (95% CI, -2.10 to -1.59 sec(-1)). RV segmental strain has a stable base-to-apex gradient that highlights the dominance of deep longitudinal layers of the right ventricle that are aligned base to apex. Variations among different normal ranges did not appear to be dependent on differences in demographic, clinical, or equipment parameters in this meta-analysis. All of the eligible studies used equipment and software from one manufacturer (GE Healthcare).
Preterm birth is associated with incident heart failure in children and young adults.
To determine the effect size of preterm birth on cardiac remodeling from birth to young adulthood.
Data sources ...include Medline, Embase, Scopus, Cochrane databases, and clinical trial registries (inception to March 25, 2020).
Studies in which cardiac phenotype was compared between preterm individuals born at <37 weeks' gestation and age-matched term controls were included.
Random-effects models were used to calculate weighted mean differences with corresponding 95% confidence intervals.
Thirty-two observational studies were included (preterm = 1471; term = 1665). All measures of left ventricular (LV) and right ventricular (RV) systolic function were lower in preterm neonates, including LV ejection fraction (
= .01). Preterm LV ejection fraction was similar from infancy, although LV stroke volume index was lower in young adulthood. Preterm LV peak early diastolic tissue velocity was lower throughout development, although preterm diastolic function worsened with higher estimated filling pressures from infancy. RV longitudinal strain was lower in preterm-born individuals of all ages, proportional to the degree of prematurity (
= 0.64;
= .002). Preterm-born individuals had persistently smaller LV internal dimensions, lower indexed LV end-diastolic volume in young adulthood, and an increase in indexed LV mass, compared with controls, of 0.71 g/m
per year from childhood (
= .007).
The influence of preterm-related complications on cardiac phenotype could not be fully explored.
Preterm-born individuals have morphologic and functional cardiac impairments across developmental stages. These changes may make the preterm heart more vulnerable to secondary insults, potentially underlying their increased risk of early heart failure.
Altit and Levy reflect on the cardiopulmonary effect of hypoxic ischemic encephalopathy (HIE) in newborn babies. They are critical on the emerging role of early hemodynamic evaluation in assessing ...the adverse neurological outcomes. Also cited is the study by Giesinger and colleagues which successfully enhanced understanding of the risk factors and postnatal adaptive processes that may linked with or predictive of infant mortality with HIE.
Preterm birth accounts for over 15 million global births per year. Perinatal interventions introduced since the early 1980s, such as antenatal glucocorticoids, surfactant, and invasive ventilation ...strategies, have dramatically improved survival of even the smallest, most vulnerable neonates. As a result, a new generation of preterm-born individuals has now reached early adulthood, and they are at increased risk of cardiovascular diseases. To better understand the sequelae of preterm birth, cardiovascular follow-up studies in adolescents and young adults born preterm have focused on characterizing changes in cardiac, vascular, and pulmonary structure and function. Being born preterm associates with a reduced cardiac reserve and smaller left and right ventricular volumes, as well as decreased vascularity, increased vascular stiffness, and higher pressure of both the pulmonary and systemic vasculature. The purpose of this review is to present major epidemiological evidence linking preterm birth with cardiovascular disease; to discuss findings from clinical studies showing a long-term impact of preterm birth on cardiac remodeling, as well as the systemic and pulmonary vascular systems; to discuss differences across gestational ages; and to consider possible driving mechanisms and therapeutic approaches for reducing cardiovascular burden in individuals born preterm.
Most epithelial tissues contain self-renewing stem cells that mature into downstream progenies with increasingly limited differentiation potential. It is not surprising that cancers arising from such ...hierarchically organized epithelial tissues retain features of cellular differentiation. Accumulating evidence suggests that the urothelium of the urinary bladder is a hierarchically organized tissue, containing tissue-specific stem cells that are important for both normal homeostasis and injury response. The phenotypic and functional properties of cancer stem cells (CSCs; also known as tumour-initiating cells) from bladder cancer tissue have been studied in detail. Urothelial CSCs are not isolated by a 'one-marker-fits-all' approach; instead, various cell surface marker combinations (possibly reflecting the cell-of-origin) are used to isolate CSCs from distinct differentiation subtypes of urothelial carcinomas. Additional CSC markers, including cytokeratin 14 (CK14), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), and tumour protein 63 (p63), have revealed prognostic value for urothelial carcinomas. Signalling pathways involved in normal stem cell self-renewal and differentiation are implicated in the malignant transformation of different subsets of urothelial carcinomas. Early expansion of primitive CK14+ cells--driven by genetic pathways such as STAT3--can lead to the development of carcinoma in situ, and CSC-enriched urothelial carcinomas are associated with poor clinical outcomes. Given that bladder CSCs are the proposed root of malignancy and drivers of cancer initiation and progression for urothelial carcinomas, these cells are ideal targets for anticancer therapies.
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 postacquisition processing is needed for reliable and reproducible measurements of myocardial deformation by two-dimensional (2D) speckle-tracking echocardiography. The aims of this study were to determine the feasibility and reproducibility of 2D speckle-tracking echocardiographic measurement of RV peak global longitudinal strain (pGLS) and peak global longitudinal strain rate in premature infants and to establish methods for acquiring and analyzing strain.
The study was designed in two phases: (1) a training phase to develop methods of image acquisition and postprocessing in a cohort of 30 premature infants (born at 28 ± 1 weeks) and (2) 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 peak global longitudinal strain rate measurements to a clinically significant level, assessed using Bland-Altman analysis (bias, limits of agreement, coefficient of variation, and intraclass correlation coefficient).
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 intraobserver (bias, 3%; 95% limits of agreement, -1.6 to +1.6; coefficient of variation, 2.7%; intraclass correlation coefficient, 0.97; P = .02) and interobserver (bias, 7%; 95% limits of agreement, -4.8 to +4.73; coefficient of variation, 3.9%; intraclass correlation coefficient, 0.93; P < .05) reproducibility, with excellent linear correlation between the two pGLS measurements (r = 0.97 P < .01 and r = 0.93 P < .05, respectively).
This study demonstrates high clinical feasibility and reproducibility of RV pGLS and RV peak global longitudinal strain rate measurements by 2D speckle-tracking echocardiography 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.
To test the hypothesis that echocardiographic markers of pulmonary vascular disease (PVD) exist in asymptomatic infants born preterm at 1-year corrected age.
We conducted a prospective cohort study ...of 80 infants born preterm (<29 weeks of gestation) and 100 age- and weight-matched infants born at term and compared broad-based conventional and quantitative echocardiographic measures of pulmonary hemodynamics at 1-year corrected age. Pulmonary artery acceleration time (PAAT), a validated index of pulmonary vascular resistance, arterial pressure, and compliance, was used to assess pulmonary hemodynamics. Lower PAAT is indicative of PVD. Subanalyses were performed in infants with bronchopulmonary dysplasia (BPD, n = 48, 59%) and/or late-onset pulmonary hypertension (n = 12, 15%).
At 1 year, there were no differences between conventional measures of pulmonary hypertension in the infants born at term and preterm. All infants born preterm had significantly lower values of PAAT than infants born at term (73 ± 8 milliseconds vs 98 ± 5 milliseconds, P < .001). Infants born preterm with BPD had even lower PAAT than those without BPD (69 ± 5 milliseconds vs 79 ± 4 milliseconds, P < .01). The degree of PVD at 1-year corrected age was inversely related to gestation in all infants born preterm. Data analysis included adjustment for ventricular function and other confounding factors.
In comparison with infants born at term, infants born preterm exhibit abnormal PAAT at 1-year corrected age irrespective of neonatal lung disease status, suggesting the existence of PVD beyond infancy. PAAT measurements offer a reliable, noninvasive tool for screening and longitudinal monitoring of pulmonary hemodynamics in infants.
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