Philip T. Levy

Normal Ranges of Right Ventricular Systolic and Diastolic Strain Measures in Children: A Systematic Review and Meta-Analysis

BACKGROUND 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. METHODS 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 Cochrans Q statistic and the inconsistency index (I(2)), and publication bias was evaluated using funnel plots and Eggers test. Effects of demographic, clinical, equipment, and software variables were assessed in a metaregression. RESULTS 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). CONCLUSIONS 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).

Feasibility and Reproducibility of Systolic Right Ventricular Strain Measurement by Speckle Tracking Echocardiography in premature infants

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 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. METHODS 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). 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 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). CONCLUSIONS 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.

Effects of Frame Rate on Two-Dimensional Speckle Tracking–Derived Measurements of Myocardial Deformation in Premature Infants

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.

Novel Echocardiography Methods in the Functional Assessment of the Newborn Heart.

Echocardiography in the neonatal intensive care unit has led to improvements in our ability to assess the neonatal heart in health and disease. Advances in neonatal cardiac imaging have provided the capability to obtain quantitative information that often supersedes the qualitative information provided by conventional methods. Novel quantitative measures of function include the assessment of the velocity of muscle tissue movement during systole and diastole using tissue Doppler velocity imaging, and evaluation of deformation and rotational characteristics of the myocardium utilizing speckle tracking echocardiography or tissue Doppler-derived strain imaging. A comprehensive understanding of these novel functional modalities, their predictive value, and limitations can greatly assist in managing both the normal and maladaptive responses in the newborn period. This article discusses the novel and emerging methods for assessment of left and right heart function in the neonatal population.

Congenital Lymphocytic Choriomeningitis Virus When to Consider the Diagnosis

Lymphocytic choriomeningitis virus is a rodent-borne arenavirus that can cause congenital infection affecting the developing central nervous system. When the infection occurs during pregnancy, the virus targets the fetal brain and retina, potentially causing ventriculomegaly, hydrocephalus, chorioretinitis, and neurodevelopmental abnormalities. It has been previously suggested that lymphocytic choriomeningitis virus be added to the list of congenital infections currently included in the TORCH acronym (toxoplasmosis, rubella, cytomegalovirus, herpes, and syphilis). We present 2 neonates with antenatally known ventriculomegaly that were diagnosed with congenital lymphocytic choriomeningitis virus infection after birth. In addition to ventriculomegaly, one had nonimmune hydrops fetalis and the other had intracranial hemorrhage. In view of the seroprevalence of lymphocytic choriomeningitis virus (4.7%-10%), our findings suggest that screening for congenital lymphocytic choriomeningitis virus infection should be considered in fetuses and newborns with ventriculomegaly as well as other abnormal neuroimaging findings such as intracranial hemorrhage.

Prenatal and Perinatal Determinants of Lung Health and Disease in Early Life: A National Heart, Lung, and Blood Institute Workshop Report

Human lung growth and development begins with preconception exposures and continues through conception and childhood into early adulthood. Numerous environmental exposures (both positive and negative) can affect lung health and disease throughout life. Infant lung health correlates with adult lung function, but significant knowledge gaps exist regarding the influence of preconception, perinatal, and postnatal exposures on general lung health throughout life. On October 1 and 2, 2015, the National Heart, Lung, and Blood Institute convened a group of extramural investigators to develop their recommendations for the direction(s) for future research in prenatal and perinatal determinants of lung health and disease in early life and to identify opportunities for scientific advancement. They identified that future investigations will need not only to examine abnormal lung development, but also to use developing technology and resources to better define normal and/or enhanced lung health. Birth cohort studies offer key opportunities to capture the important influence of preconception and obstetric risk factors on lung health, development, and disease. These studies should include well-characterized obstetrical data and comprehensive plans for prospective follow-up. The importance of continued basic science, translational, and animal studies for providing mechanisms to explain causality using new methods cannot be overemphasized. Multidisciplinary approaches involving obstetricians, neonatologists, pediatric and adult pulmonologists, and basic scientists should be encouraged to design and conduct comprehensive and impactful research on the early stages of normal and abnormal human lung growth that influence adult outcome.

Maturational Patterns of Systolic Ventricular Deformation Mechanics by Two-Dimensional Speckle-Tracking Echocardiography in Preterm Infants over the First Year of Age

Background: The aim of this study was to determine the maturational changes in systolic ventricular strain mechanics by two‐dimensional speckle‐tracking echocardiography in extremely preterm neonates from birth to 1 year of age and discern the impact of common cardiopulmonary abnormalities on the deformation measures. Methods: In a prospective multicenter study of 239 extremely preterm infants (<29 weeks gestation at birth), left ventricular (LV) global longitudinal strain (GLS) and global longitudinal systolic strain rate (GLSRs), interventricular septal wall (IVS) GLS and GLSRs, right ventricular (RV) free wall longitudinal strain and strain rate, and segmental longitudinal strain in the RV free wall, LV free wall, and IVS were serially measured on days 1, 2, and 5 to 7, at 32 and 36 weeks postmenstrual age, and at 1 year corrected age (CA). Premature infants who developed bronchopulmonary dysplasia or had echocardiographic findings of pulmonary hypertension were analyzed separately. Results: In uncomplicated preterm infants (n = 103 [48%]), LV GLS and GLSRs remained unchanged from days 5 to 7 to 1 year CA (P = .60 and P = .59). RV free wall longitudinal strain, RV free wall longitudinal strain rate, and IVS GLS and GLSRs significantly increased over the same time period (P < .01 for all measures). A significant base‐to‐apex (highest to lowest) segmental longitudinal strain gradient (P < .01) was seen in the RV free wall and a reverse apex‐to‐base gradient (P < .01) in the LV free wall. In infants with bronchopulmonary dysplasia and/or pulmonary hypertension (n = 119 [51%]), RV free wall longitudinal strain and IVS GLS were significantly lower (P < .01), LV GLS and GLSRs were similar (P = .56), and IVS segmental longitudinal strain persisted as an RV‐dominant base‐to‐apex gradient from 32 weeks postmenstrual age to 1 year CA. Conclusions: This study tracks the maturational patterns of global and regional deformation by two‐dimensional speckle‐tracking echocardiography in extremely preterm infants from birth to 1 year CA. The maturational patterns are ventricular specific. Bronchopulmonary dysplasia and pulmonary hypertension leave a negative impact on RV and IVS strain, while LV strain remains stable. HighlightsTwo‐dimensional (2D) speckle‐tracking echocardiography (STE)–derived myocardial strain is a feasible and reproducible imaging modality that can be used to characterize systolic ventricular function in premature infants.This study establishes ventricular‐specific systolic strain maturational patterns by 2D STE in a large cohort of extremely preterm infants from birth through 1 year corrected age.Common cardiopulmonary morbidities, such as bronchopulmonary dysplasia and pulmonary hypertension, appear to leave a negative impact on right ventricular strain, while left ventricular strain remains stable through the first year of age.With the establishment of the range of maturational patterns of strain mechanics and associated variations up to 1 year corrected age, deformation imaging by 2D STE may now be implemented in preterm infants as a means to identify cardiovascular compromise earlier, guide therapeutic intervention, monitor treatment response, and improve overall outcome.

Duplication of 20p12.3 associated with familial Wolff-Parkinson-White syndrome.

Wolff–Parkinson–White (WPW) syndrome is caused by preexcitation of the ventricular myocardium via an accessory pathway which increases the risk for paroxysmal supraventricular tachycardia. The condition is often sporadic and of unknown etiology in the majority of cases. Autosomal dominant inheritance and association with congenital heart defects or ventricular hypertrophy were described. Microdeletions of 20p12.3 have been associated with WPW syndrome with either cognitive dysfunction or Alagille syndrome. Here, we describe the association of 20p12.3 duplication with WPW syndrome in a patient who presented with non‐immune hydrops. Her paternal uncle carries the duplication and has attention‐deficit hyperactivity disorder and electrocardiographic findings consistent with WPW. The 769 kb duplication was detected by the Affymetrix Whole Genome‐Human SNP Array 6.0 and encompasses two genes and the first two exons of a third gene. We discuss the potential role of the genes in the duplicated region in the pathogenesis of WPW and possible neurobehavioral abnormalities. Our data provide additional support for a significant role of 20p12.3 chromosomal rearrangements in the etiology of WPW syndrome.

Novel Methods for Assessment of Right Heart Structure and Function in Pulmonary Hypertension

Long-term increases in pulmonary vascular resistance and pulmonary arterial pressure resulting from structural alterations and abnormal vasoreactivity of the pulmonary vasculature may lead to right ventricular (RV) remodeling. Conventional methods of assessment of RV structure and function do not provide sensitive markers of RV remodeling for prognostic information. Advances in cardiac imaging have provided the capability to obtain quantitative information on the RV structure and function. This article reviews the clinical conditions that result in PH and discusses the novel and emerging methods for the assessment of right heart structure and function in PH in infants and children.

Application of Neonatologist Performed Echocardiography in the Assessment and Management of Neonatal Heart Failure unrelated to Congenital Heart Disease

Neonatal heart failure (HF) is a progressive disease caused by cardiovascular and non-cardiovascular abnormalities. The most common cause of neonatal HF is structural congenital heart disease, while neonatal cardiomyopathy represents the most common cause of HF in infants with a structurally normal heart. Neonatal cardiomyopathy is a group of diseases manifesting with various morphological and functional phenotypes that affect the heart muscle and alter cardiac performance at, or soon after birth. The clinical presentation of neonates with cardiomyopathy is varied, as are the possible causes of the condition and the severity of disease presentation. Echocardiography is the selected method of choice for diagnostic evaluation, follow-up and analysis of treatment results for cardiomyopathies in neonates. Advances in neonatal echocardiography now permit a more comprehensive assessment of cardiac performance that could not be previously achieved with conventional imaging. In this review, we discuss the current and emerging echocardiographic techniques that aid in the correct diagnostic and pathophysiological assessment of some of the most common etiologies of HF that occur in neonates with a structurally normal heart and acquired cardiomyopathy and we provide recommendations for using these techniques to optimize the management of neonate with HF.