Which left atrial volume measurement should we use in the neonatal intensive care?

BACKGROUND: Increased left atrial volume (LAV) is a marker of cardiovascular risk. Echocardiography standards to assess LAV in adults and children are the biplane area-length method (AL) and method of disks (MOD). LAV in neonatology is usually derived as M-mode ratio between the LA and the Aorta (LAAo). The aim of this study is to determine feasibility and reliability of these methods in neonatal clinical practice. METHODS: Clinically indicated echocardiograms in neonatal intensive care patients were retrospectively analyzed. Feasibility was determined with an image quality score describing insonation angle, foreshortening and wall clarity. Reliability was determined with Bland-Altman and correlation coefficient analysis of intra- and inter-observer measurements. RESULTS: 104 infants ranging from 23 to 39 weeks gestation were included. The feasibility of LAAo, AL and MOD was comparable (median image score 4 out of 6 points). Linear regression between AL and MOD was excellent (R2 0.99). LAAo best-fit with MOD was reached with curve-linear regression (R2 0.28) whereby a LAAo of 1.60 correlated with 1.24 ml/kg, but with a wide 95 % CI. The correlation coefficient within and between observers for LAAo, biplane AL, biplane MOD and monoplane MOD was 0.93 (0.87-0.96), 0.98 (0.96-0.99), 0.98 (0.96-0.99), 0.99 (0.97-0.99) and 0.58 (0.11-0.81), 0.75 (0.44-0.89), 0.92 (0.88-0.98), 0.96 (0.88-0.98) respectively. CONCLUSION: All methods were equally feasible and reliable when repeated by the same observer, but LAAo reliability was poor when repeated by a different observer. Biplane MOD was the most reliable and thus recommended in neonatal practice. Monoplane MOD performed well and could be considered as alternative but might be less accurate.

Echocardiography algorithms to assess high left atrial pressure and grade diastolic function in preterm infants.

BACKGROUND: Relaxation, restoring forces, myocardial stiffness and atrial function determine left ventricular (LV) diastolic function. This study aims to provide a comprehensive assessment of diastolic function in preterm infants using conventional echocardiography and speckle tracking imaging and determine the diagnostic accuracy of various algorithms to detect high left atrial pressure (LAP). METHODS: Preterm infants received an echocardiogram 1 week after birth and diastolic reference values were derived from the outer percentiles of stable preterm infants. Impaired relaxation, LV stiffness and high LAP were defined by using algorithms where at least half of the parameters were outside the normal range. Diastolic function was graded using the 2016 American Society of Echocardiography algorithm and expanded with the EA ratio and left atrial strain. The diagnostic accuracy of various algorithms to detect high LAP was determined with sensitivity analysis. RESULTS: We studied 146 infants (59 stable) with a mean of 27(1) weeks gestation. Impaired relaxation, LV stiffness and high LAP were found in 8%, 7%, and 14% of infants. The patent ductus arteriosus was a contributing factor to high LAP and LV stiffness, not impaired relaxation. Diagnostic accuracy improved from 90% to 96% and sensitivity from 40% to 90% by adding left atrial strain to the 2016 algorithm. CONCLUSION: Various grades of diastolic dysfunction could be appreciated in preterm infants using a multi-parameter approach. Adding left atrial strain improved sensitivity to detect infants with high LAP.

The association between patterns of early respiratory disease and diastolic dysfunction in preterm infants.

BACKGROUND: This study aims to determine the association between clinical patterns of early respiratory disease and diastolic dysfunction in preterm infants. METHODS: Preterm infants <29 weeks' gestation underwent cardiac ultrasounds around day 7 and 14-21. Respiratory dysfunction patterns were classified as stable (ST), respiratory deterioration (RD) or early persistent respiratory dysfunction (EPRD) according to oxygen need. Diastolic dysfunction was diagnosed using a multi-parameter approach including left atrial strain (LASR) to help differentiate between cardiac or pulmonary pathophysiology. RESULTS: 98 infants (mean 27 weeks) were included. The prevalence of ST, RD and EPRD was 53%, 21% and 26% respectively. Diastolic dysfunction was more prevalent in the RD and EPRD groups with patent ductus arteriosus and significant growth restriction as risk factors. Not all infants with a PDA developed diastolic dysfunction. LASR was lower in the EPDR group. CONCLUSION: Respiratory dysfunction patterns are associated with diastolic dysfunction in preterm infants.

A Randomized Placebo-Controlled Pilot Trial of Early Targeted Nonsteroidal Anti-Inflammatory Drugs in Preterm Infants with a Patent Ductus Arteriosus.

OBJECTIVE: To establish the feasibility of a future large randomized trial to compare early treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) while awaiting spontaneous patent ductus arteriosus (PDA) closure. STUDY DESIGN: Preterm infants at <29 weeks of gestation with a PDA diameter >1.5 mm and <72 hours after birth were randomized to NSAIDs vs placebo. No open-label NSAID treatment was allowed in either arm, but all infants with PDA volume load received supportive management, including optimization of airway pressure, careful fluid management, and diuretics as needed. The pilot outcomes were recruitment rate and incidence of open-label treatment. Secondary clinical outcomes included chronic lung disease or death, the planned primary outcome for a future large trial. RESULTS: Overall, 54% of the approached parents consented to participate in the study. The median recruitment rate was 3 infants per month, and a total of 72 infants were randomized. One patient in each arm received open-label treatment. PDA closure rates were 74% for the NSAIDs arm vs 30% for the placebo arm, but this was not associated with significant changes in clinical outcomes. CONCLUSIONS: This pilot trial showed that recruitment of more than one-half of eligible infants with a low incidence of open-label treatment is feasible. PDA closure rates and clinical outcomes were similar to those reported in previous PDA trials.

Cardiac remodeling during the neonatal intensive care period; a window of opportunity for early prevention of heart failure?

BACKGROUND: There is growing evidence that preterm birth is a risk factor for early heart failure as a result of cardiac remodeling during a critical period of growth and development. The aim of this study was to explore if cardiac remodeling can be detected very early after preterm birth, and if present, if those remodeling changes persist until discharge. METHODS: Echocardiography parameters of left ventricular geometry and function were prospectively obtained with echocardiography in preterm infants <30 weeks gestation at postnatal day 3 and at 36 weeks postmenstrual age (PMA). Findings were compared to available data of healthy fetuses and cardiac remodeling was classified based on changes in left ventricular volume and/or mass. RESULTS: 65 (37 male) preterm infants were analysed. Three days after birth, 27.7% of infants had abnormal LV geometry, with immaturity and fetal growth restriction as risk factors for these early cardiac remodeling changes. At 36 weeks PMA, after a median period of 9 weeks of neonatal intensive care, 69.2% had abnormal cardiac geometry which could be classified as dilated hypertrophic remodeling (50.0%), dilated remodeling (11.5%) and hypertrophic remodeling (7.7%). CONCLUSION: Cardiac remodeling changes can be detected very early after preterm birth. However, most changes take place during the neonatal intensive care period. The findings of this study could assist in identifying a group where an early and short-term intervention has the potential to prevent a pathway of abnormal cardiac development.

What Inotrope and Why?

Primary function of cardiovascular system is to meet body's metabolic demands. The aim of inotrope therapy is to minimise adverse impact of cardiovascular compromise. Current use of inotropes is primarily guided by the pathophysiology of cardiovascular compromise and anticipated actions of inotropes. Lack of significant reduction in morbidity and mortality associated with cardiovascular compromise despite inotrope use, highlights major gaps in our understanding of circulatory targets, thresholds and choices of inotrope therapy. Thus far, prevention of cardiovascular compromise remains the most effective strategy to optimize outcomes. Studies of alternative design are needed for further advancement in cardiovascular therapy in neonates.

Left ventricular ejection fraction using manual and semi-automated biplane method of discs in very preterm infants.

BACKGROUND: Biplane left ventricular ejection fraction (LVEF) is a valuable echocardiographic parameter for assessment of LV systolic pump efficiency in adults and children, but not often reported in preterm infants. The primary aim of this study was to longitudinally measure biplane LVEF in very preterm infants during the neonatal intensive care period. Secondary aim was to compare manual and semi-automatic determination of LVEF for agreement and variability. METHODS: Stable preterm infants less than 30 weeks gestation were scanned on day 3, day 28, and at 36 weeks postmenstrual age. The LV endocardium was traced manually and semi-automatically using integrated speckle tracking software in apical 4-chamber and apical 3-chamber images to obtain end-diastolic volume and end-systolic volume, and calculate LVEF. Agreement between methods and variability within and between observers was determined using an interclass correlation coefficient (ICC) and Bland-Altman analysis. RESULTS: Sixty-six preterm infants with a mean birth weight of 1100 (239) g were analyzed. The average manual biplane LVEF was 58 (3)%, 59 (3)%, and 55 (4)% at the three respective time points. Manual LVEF showed good agreement with semi-automatic LVEF (ICC 0.76) with a small bias of -1.5 (3.0)%. Interobserver variability of LVEF improved with semi-automatic tracing of the LV endocardial border (ICC manual 0.68 vs semi-automatic 0.80). CONCLUSION: Left ventricular systolic pump efficiency in preterm infants remains stable during the neonatal intensive care period. Semi-automatic biplane LVEF has less interobserver variability and can be used interchangeably with manual biplane LVEF.

Standardised neonatal parenteral nutrition formulations - Australasian neonatal parenteral nutrition consensus update 2017.

BACKGROUND: The first consensus standardised neonatal parenteral nutrition formulations were implemented in many neonatal units in Australia in 2012. The current update involving 49 units from Australia, New Zealand, Singapore, Malaysia and India was conducted between September 2015 and December 2017 with the aim to review and update the 2012 formulations and guidelines. METHODS: A systematic review of available evidence for each parenteral nutrient was undertaken and new standardised formulations and guidelines were developed. RESULTS: Five existing preterm Amino acid-Dextrose formulations have been modified and two new concentrated Amino acid-Dextrose formulations added to optimise amino acid and nutrient intake according to gestation. Organic phosphate has replaced inorganic phosphate allowing for an increase in calcium and phosphate content, and acetate reduced. Lipid emulsions are unchanged, with both SMOFlipid (Fresenius Kabi, Australia) and ClinOleic (Baxter Healthcare, Australia) preparations included. The physicochemical compatibility and stability of all formulations have been tested and confirmed. Guidelines to standardise the parenteral nutrition clinical practice across facilities have also been developed. CONCLUSIONS: The 2017 PN formulations and guidelines developed by the 2017 Neonatal Parenteral Nutrition Consensus Group offer concise and practical instructions to clinicians on how to implement current and up-to-date evidence based PN to the NICU population.

Dilated hypertrophy: a distinct pattern of cardiac remodeling in preterm infants.

BACKGROUND: Young adults born preterm have remodeled hearts, i.e., altered cardiac shape and size with impaired cardiac function. At present, the natural history and pattern of prematurity related cardiac remodeling are not clearly established. The aim of this study was to compare the left ventricle (LV) geometry and function of preterm infants at 36 weeks postmenstrual age (PMA) with gestation matched newborn infants. METHODS: LV end diastolic volume index (LV EDVI), LV mass index (LVMI), relative wall thickness (RWT), and sphericity index (SI) were prospectively obtained with echocardiography. LV geometry was classified according to the Gaasch method. LV function was assessed by determining ejection fraction (EF), longitudinal strain (LS), mitral annulus systolic motion (s'), and estimated LV filling pressure (E/e'). RESULTS: Eighty-three preterm infants between 23 and 29 weeks gestation, and 40 infants of 36 weeks gestation at birth were analysed. LV EDVI, LVMI, SI, LS, s', and E/e' were higher in preterm group while RWT and EF were comparable between groups. LV showed normal geometry in 55.4%, physiological enlargement in 23% and dilated hypertrophy in 21.6% preterm infants. CONCLUSION: At 36 week, preterm infants have significantly dilated, hypertrophied, and more spherical LV with impaired diastolic function compared with PMA matched newborn infants.

Left Ventricular Diastolic Dysfunction and Diastolic Heart Failure in Preterm Infants.

Diastolic dysfunction is primarily an echocardiographic diagnosis. Its clinical counterpart is diastolic heart failure, where the heart has difficulty to fill at normal pressure and the patient develops signs of pulmonary edema. Although diastolic dysfunction is common in adults, limited information is available in preterm infants. The aim of this study is to explore left ventricular diastolic dysfunction and diastolic heart failure in preterm infants and describe clinical manifestations in this population. This is a retrospective observational study in preterm infants < 30 weeks' gestation who received an echocardiography in the first 4 weeks after birth. Diastolic dysfunction was graded using a population-specific adapted version of the adult recommendations for the evaluation of left ventricular diastolic function by echocardiography. Left ventricular diastolic dysfunction was absent, indeterminate, and definite in 82%, 14%, and 4% of the 168 echocardiograms analyzed, and is associated with increased respiratory signs and respiratory deterioration at 48 h before echocardiogram. In seven infants, diastolic heart failure was diagnosed with both ultrasound and clinical signs. The cumulative risk of diastolic dysfunction increased with the increasing postnatal age and a patent ductus arteriosus. Evidence of left ventricular diastolic dysfunction on echocardiography is relatively common in preterm infants, while the left ventricular diastolic heart failure is less frequent. Prolonged exposure to volume load was the most common cause.

Left atrium function and deformation in very preterm infants with and without volume load.

BACKGROUND: Left atrium (LA) function can be assessed by volumetric measurements, conventional and tissue Doppler, and more recently, deformation imaging using two-dimensional speckle tracking echocardiography (2DSTE). 2DSTE allows for measurement of volume and deformation and can quantify the contribution of the reservoir, conduit, and contraction phase. A common cause for LA dysfunction in very preterm infants is volume overload with a patent ductus arteriosus (PDA). The aim of this study was to explore the feasibility and reliability of LA 2DSTE in preterm infants, and describe LA function with and without PDA volume load. METHODS: We prospectively recruited preterm infants <30 weeks of gestation referred for assessment of a possible PDA. A cardiac ultrasound was performed at day 3 and in week 4 of life and analyzed using conventional techniques and 2DSTE. RESULTS: Forty-eight infants (32 with PDA) were included. LA 2DSTE analysis was feasible in 96% of measurements with good reliability of strain and volume parameters. Strain rate was less reliable. Poorer LA contraction and reservoir function was associated with larger LA volume index, higher inflow over the mitral valve at early diastole, higher EA ratio, and higher Ee' ratio. Poorer conduit function was associated with higher Ee' ratio. A larger PDA diameter was found to be an independent contributor to deteriorating LA contraction and reservoir function. CONCLUSION: LA 2DSTE analysis is feasible in preterm infants and provides detailed information on atrium mechanics. Further studies are needed to explore the clinical value of these new parameters in this population.

A comparison between Philips and Tomtec for left ventricular deformation and volume measurements in neonatal intensive care patients.

BACKGROUND: Two-dimensional speckle tracking echocardiography is an emerging technique for analyzing cardiac function in newborns. Strain is a highly reliable and reproducible parameter, and reference values have been established for term and preterm newborns. Its implementation into clinical practice has been slow, partly due to lack of inter-vendor consistency. Our aim was to compare recent versions of Philips and Tomtec speckle tracking software for deformation and semiautomated volume and area measurements in neonatal intensive care patients. METHODS AND RESULTS: Longitudinal and circumferential deformation and cavity dimensions (volume, area) were determined off line from apical and short-axis images in 50 consecutive newborns with a median birthweight of 760 g (range 460-3200 g). Absolute mean endocardial global longitudinal strain measurements were similar between vendors, but with wide limits of agreement (Philips -18.9 [2.1]%, Tomtec -18.6 [2.5]%, bias -0.3 [1.7]%, and limits of agreement -3.6%-3.1%). Longitudinal strain rate and circumferential measurements showed poor correlation. All volume and area measurements correlated well between the vendors, but with significant bias. CONCLUSION: Global longitudinal strain measurements compared well between vendors but wide limits of agreement, suggesting that longitudinal measurements are preferred using similar hardware and software.

Cardiac remodeling in preterm infants with prolonged exposure to a patent ductus arteriosus.

BACKGROUND: Sustained volume load due to a patent ductus arteriosus (PDA) leads to cardiac remodeling. Remodeling changes can become pathological and are associated with cardiovascular disease progression. Data on remodeling changes in preterm infants is not available. METHODS: Clinical and echocardiography data were collected in preterm infants <30 weeks gestation on postnatal day 3 and then every 7-14 days until closure of the ductus arteriosus. Images were analyzed using conventional techniques and speckle tracking. Remodeling changes of infants with prolonged (>14 days) exposure to a PDA were compared to control infants without a PDA. RESULTS: Thirty out of 189 infants had prolonged exposure to a PDA. The left heart remodeled to a larger and more spherical shape and thus significantly increased in volume. Most changes occurred in the first 4 weeks, plateaued, and then returned to control values. Systolic function and estimates of filling pressure increased and effective arterial elastance reduced with a PDA, however contractility was unchanged. Wall thickness increased after 4 weeks of increased volume exposure. CONCLUSION: The preterm PDA induces early and significant remodeling of the left heart. A compensated cardiac physiology was seen with preserved systolic function, suggesting adaptive rather than pathological remodeling changes with prolonged exposure to a PDA.

Post-transitional adaptation of the left heart in uncomplicated, very preterm infants.

BACKGROUND: The postnatal period in preterm infants involves multiple physiological changes occurring immediately after birth and continuing for days or weeks. To recognise and treat compromise, it is important to measure cardiovascular function. The aim of this study was to describe longitudinal left ventricular function using conventional and novel echocardiography techniques in preterm infants who did not experience significant antenatal or postnatal complications and treatments. METHODS: We prospectively obtained cardiac ultrasound images at days 3, 7, 14, 21, and 28 in 25 uncomplicated, preterm infants <30 weeks of gestation. Speckle tracking analysis of the four chambers and short-axis images provided parameters of left ventricular volume, deformation, and basal myocardial velocities. The patent ductus arteriosus, cardiac dimensions, and atrial volume were also measured. RESULTS: Stroke volume increased by 24% during the study period (1.05-1.30 ml/kg, p<0.05). Cardiac length, diameter, and systolic basal myocardial velocity increased with unchanged wall stress and deformation parameters. Diastolic function parameters resembled that of the fetus with predominance of atrial contraction compared with early diastolic velocities. Blood pressure and estimates of left ventricular filing pressure increased, suggesting that left ventricular compliance did not change in this period. CONCLUSION: Stroke volume increased in the first 28 days after preterm birth. The preterm heart adapted by increasing its size, while maintaining systolic and atrial function, independent of early diastolic maturation. Longitudinal deformation of the left ventricle remained unchanged, suggesting relatively preserved function with maturation.

Myocardial function during bradycardia events in preterm infants.

BACKGROUND: Transient bradycardia episodes are common in preterm infants and often secondary to apnea. Decreased ventilation with resultant hypoxemia is believed to be the predominant mechanism. Sudden bradycardias without apnea are also reported, possibly due to vagal stimulation. Point of care ultrasound is used to diagnose and follow cardiovascular complications in preterm infants. Inadvertently, the operator would sometimes capture bradycardia events. This study reports on left ventricular function during such events. METHODS: We retrospectively reviewed our cardiac ultrasound database for bradycardia events. Apical four or three chamber images before, during and after a bradycardia event were analysed with speckle tracking software which provides systolic and diastolic parameters of myocardial motion, deformation and volume. RESULTS: Over a 2year period, 15 bradycardia events were noted in 14 patients with a median gestational age of 26weeks (range 23 to 29). Heart rate decreased by an average of 43% (171/min to 98/min). Myocardial velocity and longitudinal strain rate during the atrial component of diastole were reduced during bradycardia. Longitudinal strain during systole was increased and radial deformation was unchanged. Ventricular volumes and ejection fraction did not change. Most parameters returned to baseline values after the event. Longitudinal systolic strain rate remained lower and stroke volume was 12% higher compared to baseline. CONCLUSION: Parameters of systolic contractility and stroke volume were maintained and parameters of atrial contractility were reduced during mild to moderate bradycardia in preterm infants. Bradycardia reduces total cardiac output with a compensatory increase detected following the event.

Cardiac Function After the Immediate Transitional Period in Very Preterm Infants Using Speckle Tracking Analysis.

BACKGROUND: The postnatal period in preterm infants involves multiple physiologic changes starting directly after birth and continuing for days or weeks. To recognize and treat compromise, it is important to measure cardiovascular function. We used a novel technique (speckle tracking echocardiography, STE) to measure cardiac function in this period. METHODS: We obtained cardiac ultrasound images at day 3, 7, 14, 21 and 28 in preterm infants <30-week gestation. Conventional measures included cardiac size, left ventricular stroke volume, atrial volume and the patent ductus arteriosus (PDA). Four chamber images were analyzed with STE, which provided parameters of left ventricular volume, longitudinal deformation and myocardial velocities. RESULTS: Images of 54 infants (gestational age 23-29 weeks) were analyzed. STE-derived stroke volume correlated well with conventional echocardiography-derived stroke volume, but agreement was suboptimal. Most STE parameters showed good reliability. All volume parameters and systolic and atrial velocities increased over time. Cardiac deformation and early diastolic velocity did not change. A PDA was associated with 33 % increased stroke volume at day 3 up to 98 % at day 28 with a spherically enlarged heart and increased filling pressure. CONCLUSION: Speckle tracking echocardiography analysis is a feasible and reliable technique that can simultaneously obtain systolic and diastolic volumes, longitudinal deformation and myocardial velocities from one ultrasound window. Preterm hearts maintain cardiac function well during the first weeks of life, even with increased preload as a consequence of a PDA.

Intestinal strictures post-necrotising enterocolitis: clinical profile and risk factors.

BACKGROUND: Intestinal stricture is an important complication of necrotising enterocolitis (NEC). We aimed to describe clinical profile and identify the risk factors for post-NEC intestinal strictures. METHOD: A retrospective study of infants with NEC over 10 year period. RESULTS: Of the 61 infants with NEC, 18 (29.5%) developed intestinal strictures. Leucocytosis and longer length of bowel resection during acute stage of NEC was associated with a later diagnosis of intestinal stricture. Infants with NEC who did not develop stricture had non-specific intestinal dilatation on abdominal x-ray during acute NEC. Intestinal strictures were diagnosed at a median interval of 34 days after NEC. Majority of strictures (67%) occurred in the colon. A significant proportion (77%) of infants with intestinal stricture had associated co-morbidities. No mortality occurred in infants with intestinal strictures. CONCLUSION: The incidence of post-NEC intestinal stricture is high but development of stricture is difficult to predict. Leucocytosis during NEC and length of bowel resected at surgery may be associated with development of post-NEC intestinal stricture. A substantial number of infants with post-NEC intestinal stricture fail to thrive, have co-morbidities and need prolonged hospitalisation.