A Comprehensive Echocardiographic Assessment of Neonatal Right Ventricular Function in Neonatal Intensive Care Unit Babies

Background The right ventricle (RV) in the fetus is the predominant chamber, accounting for about 60% of the total cardiac output. The majority of the RV outflow volume is diverted from the pulmonary artery via the ductus arteriosus to the descending aorta. After birth, the RV undergoes extensive structural and functional modifications. The RV undergoes an improper transition from fetal to neonatal circulation in sick neonatal intensive care unit (NICU) babies. Functional echocardiography is now commonly being used in most NICUs as it is a noninvasive and bedside investigation that gives an immediate evaluation of hemodynamics and can be taken into consideration as an extension of clinical assessment to study a critically unwell neonate. Therefore, a study of RV functions in NICU neonates will help in better understanding the neonatal cardiopulmonary response to different diseases. Thus, this study aimed to assess RV functions in neonates getting admitted to the NICU of a tertiary care institute. Methodology This observational, cross-sectional study was approved by the Research & Recognition Committee of Dr. D. Y. Patil Vidyapeeth, Pune. In total, 35 cases of term neonates admitted to the NICU at Dr. D. Y. Patil Medical College, Hospital & Research Centre, Pune who fulfilled the inclusion criteria were enrolled in this study after obtaining consent from their parents. Two-dimensional echocardiography was performed by a trained pediatric cardiologist, and the findings were substantiated by a neonatologist trained in echocardiography. Results Our study found a strong association between tricuspid inflow velocity and neonates with sepsis. Similarly, a significant association was observed between abnormal tricuspid Inflow velocity (E/A and E/E’) and neonates requiring inotropic support. Conclusions Data on the normal values of different echocardiographic parameters of the systolic and diastolic function of the RV during the neonatal phase of life are currently limited. Our data offer preliminary insights into this topic. Early echocardiography and intervention are advisable, especially in neonates with sepsis and requiring inotropic support.


Introduction
The cardiovascular system of neonates is not a miniature version of the mature human body. The fetal heart is functionally adapted to a low-pressure environment with high pulmonary blood flow and low systemic vascular resistance [1]. For a successful transition from intrauterine to extrauterine life, birth requires a variety of circulatory changes. In addition to the radical adaptation to an extrauterine circulation after delivery, the newborn heart must adapt promptly to a dual circulation with much greater systemic vascular resistance and increased metabolic needs [1].
The early indicators of altered function in the fetal heart are now believed to be a reflection of right heart hemodynamics. Observations indicate that the right ventricle (RV) of the embryonic heart contributes significantly to the work output of the fetal myocardium due to the tremendous volume and pressure work necessitated by it. Echocardiography is a vital investigative tool in the neonatal intensive care unit (NICU), which immensely facilitates the evaluation of the neonate. Recently published studies have provided evidence that demonstrates the significance of using echocardiography in the treatment of critically ill patients. According to studies, clinical therapy is altered in 30-60% of patients after point-of-care echocardiography, and this technique is currently regarded as an essential tool in the management of sick neonates [2,3].
Tricuspid annular plane systolic excursion (TAPSE) or S' wave on tissue Doppler imaging are good reflectors of RV systolic function and can be reliably performed using bedside functional echocardiography [4,5]. It measures the excursion of the tricuspid annulus during the cardiac cycle (between early diastole and end systole). A relatively new measurement of ventricular function, the myocardial performance index (MPI), has been shown to correlate with other quantifiable, noninvasive, and invasive measures of ventricular function [6][7][8][9][10]. The MPI is a ratio and is derived by dividing the total time spent in isovolumic activity (isovolumic contraction time and isovolumic relaxation time) by the time spent in ventricular ejection.
The left ventricle has been more widely studied compared to the RV. In our view, the RV is equally important because, after birth, the RV undergoes an improper transition from fetal to neonatal circulation in sick NICU babies. Therefore, a study of RV functions in NICU neonates will help in better understanding the neonatal cardiopulmonary response to different diseases. Thus, this study aimed to assess RV functions in neonates admitted to the NICU of a tertiary care institute.

Materials And Methods
In this observational, cross-sectional study, 35 neonates who were admitted to the Level III NICU of Dr. D Y Patil Medical College, Hospital & Research Centre, Pimpri during two years were evaluated with bedside echocardiography to assess RV function. The study was conducted after obtaining approval from the Research & Recognition Committee (approval ID: IESC/PGS/2020/40) and informed consent from parents. Two-dimensional echocardiography was performed by a trained pediatric cardiologist, and the findings were substantiated by a neonatologist trained in echocardiography. Two-dimensional echocardiography was performed using Fujifilm Sonosite Edge II (serial number: Q53FGW), which was calibrated regularly.
After birth, the RV undergoes extensive structural and functional modifications. There is a progressive decrease in RV wall thickness and growth in left ventricular mass after birth due to the marked fall in pulmonary vascular resistance (PVR) and increased systemic vascular resistance (SVR). Unlike modifications in the RV during the normal transition, RV hypertrophy persists in case of sustained elevations of PVR, persistent pulmonary hypertension of the newborn, congenital coronary heart disease, and other cardiopulmonary disorders. RV adaptation and/or maladaptation may play a role in the clinical condition of the baby and needs to be studied in detail. Hence, this study would help us understand the underlying RV dysfunction of the neonate and its impact on the clinical outcome.
Term neonates admitted to NICU at Dr. D Y Patil Medical College, Hospital & Research Centre, Pimpri needing oxygen therapy, inotropic support, prolonged antibiotic therapy, and/or exchange transfusion were included in the study. Preterm babies, babies with congenital heart disease, and babies of HIV-positive mothers were excluded from the study. RV function was assessed by measuring TAPSE, tricuspid inflow velocities (E/A and E/E'), and MPI. Term neonates admitted to the NICU who fulfilled the inclusion criteria were included in this study. The detailed study procedure was explained to the parents of the neonates eligible for the study in a language they understood and written informed consent was taken before the commencement of the study. Data was collected in a preformed data collection form and entered in Microsoft Excel. The study statistics are presented in the form of numbers and percentages for qualitative data and quantitative data. Mean and standard deviation were used. Appropriate statistical tests such as the chi-square test and p-value were applied. SPSS software version 26 (IBM Corp., Armonk, NY, USA) was used for data analysis.

Results
Of the 35 cases in this study, RV function was assessed using parameters such as tricuspid inflow velocity, RV MPI, and TAPSE and was categorized according to the etiology of admission. Table 1 shows the distribution of study participants according to etiology. However, an overlap of etiology was seen in some patients.  The most common etiology observed for NICU admission was meconium aspiration syndrome (57.1%), followed by perinatal hypoxia (40%), sepsis (31.5%), and pathological jaundice (17.1%).
The RV function was assessed using various modalities such as TAPSE, tricuspid inflow velocities, and MPI, as shown in Table 2.  In our study, most cases had observed values near the reference range except tricuspid inflow velocity (E/A), which were lower than the reference range, and RV MPI was observed to be higher than the reference range. Table 3 shows the RV function (assessed using tricuspid inflow velocity -E/A and E/E') observed in our study participants along with its comparison with the reference range.       association was observed between abnormal tricuspid inflow velocity (E/A and E/E') and neonates requiring inotropic support with a significant p-value of 0.005 and 0.053, respectively. It was observed that among those having abnormal E/A ratio, most were increased, whereas the majority of those having abnormal E/E' had decreased values. Of those on inotropic support, there was a statistically significant association between tricuspid inflow velocity (E/A) and neonates on monotherapy inotropic support with a significant p-value of 0.040. Similarly, there was no association between TAPSE and neonates on polytherapy inotropic support with a significant p-value of 0.011. Early inotropic support may be beneficial for the overall outcome/condition of the baby.

Discussion
The role of echocardiography in the NICU has changed over the past few years. More recently, neonatologists have become interested in the echocardiographic assessment of hemodynamic instability in infants. The terms functional echocardiography and point-of-care echocardiography have been introduced to describe the use of echocardiography as an adjunct in the clinical assessment of the hemodynamic status in neonates. The increasing availability of echocardiography, with the miniaturization of the technology, has resulted in the more widespread use of echocardiography in NICUs globally. In addition, newborns in the NICU are unique as they are in the process of transition from fetal to postnatal circulation.
In our study, the most common etiology observed for NICU admission was meconium aspiration syndrome (57.1%), followed by perinatal hypoxia (40.3%), sepsis (31.5%), and pathological jaundice (17.1%). Most study participants had observed values near the reference range except tricuspid inflow velocity (E/A), which was found to be lower than the reference range, and RV MPI, which was observed to be higher than the reference range. The reference ranges were reported in the study by Pedraza-Melchor et al. who assessed the RV anatomical and functional parameters in healthy term neonates, by Mah et al. who assessed the RV function of patients with pediatric heart disease, and by Smith et al. who assessed the RV function of healthy term neonates [11][12][13]. Figure 1 shows the assessment of the RV function by tricuspid inflow velocity (E' value).   In our study, a strong association was noted between tricuspid inflow velocity and neonates with sepsis (six abnormal values were observed, of which four were increased). Vallabhajosyula et al. studied RV dysfunction in septic patients. It was found that isolated RV dysfunction is seen commonly in sepsis and septic shock and is associated with worse long-term survival. RV dysfunction in sepsis is multifactorial and can be caused by direct myocardial depression, hemodynamic derangements or an increase in RV afterload due to hypoxemia, hypercapnia, and mechanical ventilation for acute respiratory failure [11]. Sobeih et al. evaluated the echocardiographic parameters in 20 neonates with perinatal asphyxia (cases) and 20 healthy full-term nonasphyxiated neonates (controls). Among pulsed-wave Doppler parameters, cases had statistically significant lower values than controls for mitral E velocity and mitral E/A ratio. Similarly, among tissue Doppler parameters, cases had statistically significant lower values than controls for septal E'/A' ratio, left ventricular E' velocity, and E'/A' ratio [14]. Peček et al. quantitatively characterized changes in RV function using echocardiography in 35 healthy term newborns between the third and the seventh day of life. They concluded that increased RV systolic and diastolic myocardial velocities, cardiac output and longitudinal deformation, and decreased RV MPI' between the third and the seventh day of life point to a reduction of RV afterload and adaptive myocardial maturation in term newborns during this period. Hence, early echocardiography and intervention may help in the overall clinical outcomes of the patient [15]. Figure 3 shows the assessment of the RV function by tricuspid inflow velocity (E/A value).