Adam T. James

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.

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.

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.

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.

Treatment of premature infants with pulmonary hypertension and right ventricular dysfunction with milrinone: a case series

Objective:Milrinone has been proposed as an effective treatment for pulmonary hypertension (PH) and right ventricular (RV) dysfunction. We aimed to determine the effect of milrinone therapy on clinical and echocardiography parameters of PH in preterm infants with elevated pulmonary pressures.Study Design:A retrospective case review was conducted on infants <32 weeks gestation who received milrinone for the treatment of PH and reduced RV function. Echocardiographic data were collected before and after treatment with milrinone, and serial clinical parameters were recorded over a 72h  period.Result:Seven infants met the inclusion criteria with a median gestation and birth weight of 27.3 weeks and 1140 g, respectively. Four infants had a diagnosis of pulmonary hypoplasia with PH, and three infants were recipients in twin-to-twin transfusion syndrome who also developed PH. Nitric oxide was used in six infants before commencement of milrinone. Milrinone was commenced at a dose of 0.33 μg kg−1 min−1 to 0.5 μg kg−1 min−1 and continued for a median duration of 70 h. Use of milrinone was associated with a fall in oxygenation index and inhaled nitric oxide dose. Following an initial fall in blood pressure over the first 6 h, there was an increase in blood pressure over the subsequent 72 h. Echocardiographic data demonstrated an increase in indicators of myocardial performance and PH. One infant died before discharge.Conclusion:This case series suggests that milrinone may be a useful therapy for premature infants with echocardiography findings of PH and/or RH dysfunction. This data support the need for a randomised control trial to confirm its efficacy.

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.

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.

The effect of antenatal magnesium sulfate on left ventricular afterload and myocardial function measured using deformation and rotational mechanics imaging

Objective:Assess the effect of antenatal magnesium sulfate (MgSO4) on left ventricular function measured using deformation and rotational mechanics imaging.Study Design:Infants who received MgSO4 were matched for gestation, birth weight and mode of delivery with controls. Echocardiography was carried out on days 1 and 2 to measure left ventricle longitudinal strain (LV LS), twist, untwist rate, ejection fraction (EF), and systemic vascular resistance (SVR).Results:Thirty-eight infants with a median gestation and birth weight of 27.1 weeks and 923 g were included. On day 1, the MgSO4 group (n=19) had a lower SVR and higher LV LS, EF, twist and untwist rate than the Control group (n=19) (all P<0.05). There were no differences between the groups on day 2.Conclusion:Antenatal MgSO4 administration is associated with a lower SVR and higher myocardial function on day 1 in preterm infants <29 weeks gestation.

Serial measures of cardiac performance using tissue Doppler imaging velocity in preterm infants < 29 weeks gestations

INTRODUCTION Tissue Doppler imaging (TDI) is a useful marker of myocardial performance in preterm infants. We aimed to demonstrate serial changes in TDI velocity in preterm infants <29weeks gestation, to assess the impact of inotropes and a haemodynamically significant patent ductus arteriosus (hsPDA). METHODS This was a prospective observational study of preterm infants <29weeks gestation. Echocardiography was performed at days 1, 2, 5-7 and at 36weeks, or before hospital discharge. Infants with hsPDAs on day 5-7 and those who received inotropes in the first week of life were not included in the Reference Cohort. Systolic (s`) and diastolic (e` and a`) velocity waves were assessed at the mitral and tricuspid annulus and basal septum. RESULTS One hundred and thirty nine infants with a mean (SD) gestation and birthweight of 26.7 (1.5) weeks and 946 (247) grams were enrolled. The 66 infants (47%) in the Reference Cohort demonstrated an increase in functional parameters with increasing age [LV s`, Septal s`, and RV s`, Day 1-36weeks: 2.8 (0.6) to 4.7 (1.0), 2.4 (0.6) to 4.6 (0.8), 3.6 (0.6) to 6.9 (1.0) cm/s respectively; all p<0.05). The 24 infants who received inotropes had lower LV e` [2.9 vs. 3.6cm/s], Septal e` [2.3 vs. 2.8cm/s] and a` [3.2 vs. 3.9cm/s], and lower RV a` [3.3 vs. 3.9cm/s] on Day 1 (all p<0.05). Fifty five infants had a hsPDA on Day 5-7, demonstrating higher LV [4.7 vs. 4.0cm/s] and Septal e` [3.9 vs. 3.3cm/s], and a higher LV E/e` [13 vs. 10] (all p<0.05). CONCLUSION Extremely preterm infants display a gradual increase in tissue Doppler velocities from birth until 36weeks corrected age. The presence of a hsPDA increases diastolic TDI velocities. Infants requiring inotropes have lower diastolic myocardial velocities on Day 1.

PC.40 Assessment of Myocardial Performance using Novel Echocardiography Markers in Infants less than 29 Weeks Gestation during the Transitional Period

Introduction Physiological changes of the preterm heart during the transitioning period are a challenging area to assess. Colour Tissue Doppler derived longitudinal strain (LS) and strain rate (SR) as well as tricuspid annulus plane systolic excursion (TAPSE) and fractional area change (FAC) are novel echocardiographic techniques for the assessment of left (LV) and Right (RV) ventricular function. We aimed to assess the feasibility and reliability of measuring these indices in preterm infants less than 29 weeks gestation during the transitioning period. Methods A prospective study was conducted on 54 preterm infants, with a mean (SD) gestation and birth weight of 26.7 (1.4) weeks and 954 (231) grams. LS, SR, conventional markers and novel RV markers were measured at a mean of 10 and 45 h of life. Reliability was assessed by using intra class correlation coefficient (ICC) and Bland-Altman Analysis. Results Despite no significant change in conventional markers such as shortening fraction or ejection fraction, there was a significant increase in septal SR(-1.6 to -1.8, p = 0.002) and SRE(1.7 to 2.2, p = 0.002) across the two time points. RV function parameters including SR, SRA, TAPSE, and FAC demonstrated a significant increase across the two time points. Septal and RV function and dimension parameters demonstrated excellent reliability results. Conclusion Myocardial deformation including strain, strain rate was as well as RV markers and dimensions were feasible in infants less than 29 weeks gestation. Significant changes were seen using novel echocardiographic markers over the transitional period.