Echocardiographic Assessment of Right Ventricular Afterload in Preterm Infants: Maturational Patterns of Pulmonary Artery Acceleration Time Over the First Year of Age and Implications for Pulmonary Hypertension.

BACKGROUND: Assessment of pulmonary hemodynamics is critical in the diagnosis and management of cardiopulmonary disease of premature infants, but reliable noninvasive indices of pulmonary hemodynamics in preterm infants are lacking. Because pulmonary artery acceleration time (PAAT) is a validated noninvasive method to assess right ventricular (RV) afterload in infants and children, the aim of this study was to investigate the maturational changes of PAAT measures in preterm infants over the first year of age and to discern the impact of typical cardiopulmonary abnormalities on these measures. METHODS: In a prospective multicenter study of 239 preterm infants (<29 weeks at birth), PAAT was assessed at days 1, 2, and 5 to 7, at 32 and 36 weeks' postmenstrual age, and at 1-year corrected age. To account for heart rate variability, PAAT was adjusted for RV ejection time. Premature infants who developed bronchopulmonary dysplasia or had echocardiographic findings of pulmonary hypertension were analyzed separately. Intra- and interobserver reproducibility analysis was performed. RESULTS: PAAT was feasible in 95% of the image acquisitions, and there was high intra- and interobserver agreement (intraclass correlation coefficients > 0.9 and coefficients of variation < 6%). In uncomplicated preterm infants (n = 103 [48%]) PAAT and PAAT adjusted for RV ejection time increased longitudinally from birth to 1-year corrected age (P < .001) and were linearly associated with gestational age at birth (r = 0.81 and r = 0.82, P < .001) and increasing postnatal weight and postnatal age (r > 0.81, P < .001). PAAT measures were significantly reduced (P < .001) in infants with bronchopulmonary dysplasia and/or pulmonary hypertension (n = 119 [51%]) beyond 1 week of age. CONCLUSIONS: PAAT measures increase in preterm infants from birth to 1-year corrected age, reflective of the physiologic postnatal drop in RV afterload. Bronchopulmonary dysplasia and pulmonary hypertension have a negative impact on PAAT measures. By demonstrating excellent reliability and establishing reference patterns of PAAT in preterm infants, this study suggests that PAAT and PAAT adjusted for RV ejection time can be used as complementary parameters to assess physiologic and pathologic changes in pulmonary hemodynamics in neonates.

Incidental Findings on Routine Targeted Neonatal Echocardiography Performed in Preterm Neonates Younger Than 29 Weeks' Gestation.

OBJECTIVES: The aim of this study was to quantify the rate of incidental findings identified on elective research echocardiography performed on neonates younger than 29 weeks' gestation. METHODS: We conducted a retrospective study of echocardiographic examinations performed within the first 24 hours of age on neonates younger than 29 weeks' gestation over a 3-year period for research purposes. Incidental echocardiographic findings and pertinent clinical data were recorded. RESULTS: Echocardiographic examinations performed on 145 neonates were retrospectively reviewed. Forty-three neonates (30%) had a total of 54 unexpected findings (37%). Most comprised malpositioned umbilical venous catheters, where the tip was located in the left atrium. The remainder of the conditions identified included unsuspected congenital heart disease, liver hematomas, and unexpected pulmonary hypertension. CONCLUSIONS: There is a high rate of incidental findings identified on screening echocardiograms. Routine targeted neonatal echocardiographic screening of preterm neonates may be warranted to identify the considerable likelihood of asymptomatic findings.

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.

The impact of a hyperdynamic left ventricle on right ventricular function measurements in preterm infants with a patent ductus arteriosus.

BACKGROUND AND AIMS: Right ventricular (RV) functional assessment in premature infants includes basal longitudinal strain (RV BLS), RV systolic tissue Doppler velocity (RV s'), tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change (FAC). A hyperdynamic left ventricle (LV) may influence RV measures of displacement (TAPSE) and velocity (RV s') but not measures of relative change of length (RV BLS) or area (FAC). We aimed to explore this hypothesis in preterm infants with a patent ductus arteriosus (PDA). METHODS: We measured LV function (ejection fraction (LV EF); left ventricular output) and RV function (RV BLS; RV s'; TAPSE; FAC) on days 1, 2 and 5-7 in infants <29 weeks. The cohort was divided based on PDA presence by days 5-7. LV and RV function measurements were compared between the groups using two-way analysis of variance with repeated measures. RESULTS: 121 infants with a mean (SD) gestation and birth weight of 26.8 (1.4) weeks and 968 (250) g were enrolled. By days 5-7, the PDA remained open in 83 (69%), with evidence of hyperdynamic LV function. There was no difference in RV s' (5.3 (0.9) vs 5.1 (1.0) cm/s, p=0.3) or TAPSE (6.2 (1.3) vs 6.1 (1.2) mm, p=0.7) between infants with and without a PDA, but infants in the PDA group had lower RV FAC (41 (8) vs 47 (10) %, p<0.01) and lower RV BLS (-24.2 (5.0) vs -26.2 (4.1) %, p=0.03). CONCLUSIONS: LV influence on RV functional parameters must be taken into account when interpreting of RV function using those techniques.

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.

Longitudinal Assessment of Left and Right Myocardial Function in Preterm Infants Using Strain and Strain Rate Imaging.

BACKGROUND: There is a paucity of longitudinal data on left ventricular (LV) and right ventricular (RV) function in preterm infants of less than 29 weeks' gestation. OBJECTIVE: The aim of this study was to describe changes in tissue Doppler-derived basal longitudinal strain (BLS) and systolic (SRs), early (SRe) and late (SRa) diastolic strain rates in extremely premature infants from birth to 36 weeks postmenstrual age (PMA). METHODS: Echocardiographic assessments were carried out on days 1, 2, 5-7 and at 36 weeks PMA. We assessed the following associations: correlation with systemic vascular resistance (SVR) on day 1, influence of a patent ductus arteriosus (PDA) during days 5-7, and the effect of chronic lung disease (CLD). RESULTS: In total, 105 infants with a median gestation of 27.1 weeks (IQR 26.0-28.1) and a birthweight of 965 g (IQR 785-1,153) were included. There was an increase in most of the measurements across the four time points. On day 1, there was a weak negative correlation between SVR and LV BLS (r = -0.3, p = 0.01), SVR and septal BLS (r = -0.4, p < 0.001) and SVR and LV SRe (r = -0.4, p = 0.005). On days 5-7, infants with a PDA >1.5 mm had higher LV BLS [-13.0 (2.4) vs. -11.9 (1.9)%, p = 0.03]. At 36 weeks, infants with CLD (n = 28/47) had lower RV BLS [-26.4 (5.0) vs. -30.7 (5.5)%, p = 0.01] and lower RV SRa [4.2 (1.3) vs. 5.3 (1.9) s-1, p = 0.04]. CONCLUSION: Myocardial function undergoes important longitudinal changes in preterm infants. Left heart strain measurements appear to be weakly influenced by changes in preload and afterload. CLD appears to leave a negative impact on RV function.

The effect of milrinone on right and left ventricular function when used as a rescue therapy for term infants with pulmonary hypertension.

INTRODUCTION: Milrinone may be an appropriate adjuvant therapy for infants with persistent pulmonary hypertension of the newborn. We aimed to describe the effect of milrinone administration on right and left ventricular function in infants with persistent pulmonary hypertension not responding to inhaled nitric oxide after 4 hours of administration. MATERIALS AND METHODS: This is a retrospective review of infants born after or at 34 weeks of gestation with persistent pulmonary hypertension who received milrinone treatment. The primary endpoint was the effect of milrinone on myocardial performance and haemodynamics, including right and left ventricular outputs, tissue Doppler velocities, right ventricle and septal strain, and strain rate. Secondary endpoints examined included duration of inhaled nitric oxide and oxygen support. RESULTS: A total of 17 infants with a mean (standard deviation) gestation and birth weight of 39.8 (2.0) weeks and 3.45 (0.39) kilograms, respectively, were included in the study. The first echocardiogram was performed 15 hours after the commencement of nitric oxide inhalation. Milrinone treatment was started at a median time of 1 hour after the echocardiogram and was associated with an increase in left ventricular output (p=0.04), right ventricular output (p=0.004), right ventricle strain (p=0.01) and strain rate (p=0.002), and left ventricle s` (p<0.001) and a` (p=0.02) waves. There was a reduction in nitric oxide dose and oxygen requirement over the subsequent 72 hours (all p<0.05). CONCLUSION: The use of milrinone as an adjunct to nitric oxide is worth further exploration, with preliminary evidence suggesting an improvement in both oxygenation and myocardial performance in this group of infants.

Clinical utility of right ventricular fractional area change in preterm infants.

INTRODUCTION: Right ventricular fractional area change (RV FAC) is a novel non-invasive quantitative measure of RV function. Reference values of RV FAC and RV end systolic and diastolic areas (RVEDA, RVESA) have recently been established in preterm infants, but their role as marker to assess the efficacy of patient management strategies in the first week of life is largely unknown. The aims of this study were to assess the relationship between RV FAC and gestational age/birthweight, assess the RV FAC on day one of age to predict the later evolution of peri/intraventricular haemorrhage (P/IVH), and assess the influence of a persistent patent ductus arteriosus (PDA) on RV FAC during the first week of age. METHODS: Preterm infants <29 weeks gestation underwent echocardiography assessments on days 1, 2 and 5-7. RVEDA and RVESA were traced in the RV-focused apical four-chamber view, and RV FAC was calculated using the formula [(RVEDA-RVESA)÷(RVEDA)] × 100. PDA treatment was not carried out during the study period. A cranial ultrasound was carried out on all infants on Days 5-7 of age. P/IVH was defined as IVH grades II to IV. RESULTS: One hundred and one infants with a mean gestation of 26.5 (1.4) weeks and a birthweight of 983 (240) grams were enrolled in the study. There was no relationship between RV FAC and birthweight (r=-0.02, p=0.86) but there was a negative correlation between RV FAC and echo-measured SVR (r=-0.57, p<0.001). On Day 1, RV FAC was lower in infants who developed P/IVH (24% [18-34] vs. 31% [25-40], p=0.04). On Days 5-7 infants with a PDA had a lower RV FAC compared with those without [42 (7) vs. 49 (9) %, p<0.001]. CONCLUSION: RV FAC may be a useful addition to the haemodynamic assessment of preterm infants during the first week of age.

A Patent Ductus Arteriosus Severity Score Predicts Chronic Lung Disease or Death before Discharge.

OBJECTIVES: To test the hypothesis that a patent ductus arteriosus (PDA) severity score (PDAsc) incorporating markers of pulmonary overcirculation and left ventricular (LV) diastolic function can predict chronic lung disease or death before discharge (CLD/death). STUDY DESIGN: A multicenter prospective observational study was conducted for infants <29 weeks gestation. An echocardiogram was carried out on day 2 to measure PDA diameter and maximum flow velocity, LV output, diastolic flow in the descending aorta and celiac trunk, and variables of LV function using tissue Doppler imaging. Predictors of CLD/death were identified using logistic regression methods. A PDAsc was created and a receiver operating characteristic curve was constructed to assess its ability to predict CLD/death. RESULTS: We studied 141 infants at a mean (SD) gestation and birthweight of 26 (1.4) weeks and 952 (235) g, respectively. Five variables were identified that were independently associated with CLD/death (gestation at birth, PDA diameter, maximum flow velocity, LV output, and LV a' wave). The PDAsc had a range from 0 (low risk) to 13 (high risk). Infants who developed CLD/death had a higher score than those who did not (7.3 [1.8] vs 3.8 [2.0], P < .001). PDAsc had an area under the curve of 0.92 (95% CI 0.86-0.97, P < .001) for the ability to predict CLD/death. A PDAsc cut-off of 5 has sensitivity and specificity of 92% and 87%, and positive and negative predictive values of 92% and 82%, respectively. CONCLUSIONS: A PDAsc on day 2 can predict the later occurrence of CLD/death further highlighting the association between PDA significance and morbidity.

Late medical therapy of patent ductus arteriosus using intravenous paracetamol.

OBJECTIVE: To investigate the effect of late treatment with intravenous paracetamol on patent ductus arteriosus (PDA) closure prior to possible PDA ligation. METHODS: A retrospective review of infants with a haemodynamically significant PDA, considered for PDA ligation and treated with intravenous paracetamol prior to possible ligation. RESULTS: Thirty six infants with a median gestation of 26.1 weeks received paracetamol at a median age of 27 days. Paracetamol was associated with immediate closure in nine (25%) infants. There was no response to paracetamol treatment in four (11%) infants who subsequently underwent a PDA ligation. In 23 (64%) infants, the PDA constricted and all but one of this group demonstrated complete PDA closure prior to discharge. CONCLUSIONS: There may be a role for intravenous paracetamol in late closure of infants with a significant PDA to avoid ligation. The use of paracetamol for late treatment of PDA should be systematically evaluated.

Assessment of myocardial performance in preterm infants less than 29 weeks gestation during the transitional period.

BACKGROUND: The transitional circulation and its effect on myocardial performance are poorly understood in preterm infants. AIMS: We assessed myocardial performance in infants less than 29 weeks gestation in the first 48 h of life using a comprehensive echocardiographic assessment. DESIGN: Infants <29 weeks gestation were prospectively enrolled. Small for gestation, infants on inotropes and/or inhaled nitric oxide and septic infants were excluded. Conventional echocardiography, left ventricular (LV), septal and right ventricular (RV) tissue Doppler imaging (TDI) and tissue Doppler-derived strain and strain rate (SR), tricuspid annular plane systolic excursion (TAPSE) and global RV fractional area change (FAC) were assessed at a median of 10 and 45 h post-delivery. RESULTS: Fifty-four infants with a median [IQR] gestation and birth weight of 26.5 weeks [25.8-28.0 weeks] and 915 g [758-1142 g] were included. There was no change in shortening or ejection fraction across the two time points. Systolic and diastolic TDI of the LV, septum and RV increased across the two time points (all p values ≤ 0.01). There was an increase in septal peak systolic and early diastolic SR (p=0.002). Septal systolic strain and late diastolic SR did not change. With the exception of RV strain and early diastolic SR, all RV functional parameters including SR, late diastolic SR, TAPSE, and FAC increased across the two time points (all p values<0.01). CONCLUSION: Describing the normal hemodynamic adaptations in stable preterm infants during the transitional period provides the necessary information for the assessment of those parameters in various disease states.