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Background: Subjective assessment of right ventricular (RV) function by neonatal echocardiography lacks validation. Incorrect diagnostic assignment in patients with suspected pulmonary hypertension (PH) may lead to unnecessary treatment or missed treatment opportunities., Methods: Six evaluators (experts [n = 3], novice [n = 3]) were asked to independently rate RV characteristics (global function, dilation, and septal flattening) based on standardized echocardiography images. We randomly selected 60 infants, ≥35 weeks gestation at birth, of whom 30 were clinically unwell with acute pulmonary hypertension (aPH) and 30 were healthy controls. aPH was defined by echocardiography presence of right-left shunting across transitional shunts or elevated right ventricular systolic pressure as estimated by the magnitude of the regurgitant jet across the tricuspid valve with impaired oxygenation. Inter-rater comparative evaluation within groups and between groups was performed using Kappa statistics., Results: Global agreement between evaluators for subjective assessment of RV function (0.3 [0.03], P < 0.001), size (0.14 [0.02], P < 0.001), and septal flattening (0.2 [0.02], P < 0.001) was uniformly poor. Agreement in RV function assessment was marginally better for both expert (0.32 [0.08], P < 0.001 vs 0.13 [0.081], and P < 0.001) and novice (0.4 [0.08], P < 0.001 vs 0.06 [0.07], and P < 0.001) evaluators. Overall, the diagnosis of aPH vs control was misclassified in 18% of cases., Conclusion: This study demonstrated significant variability in qualitative assessment of RV size and function by trained evaluators, regardless of level of expertise attained. The reliability of objective measures of RV hemodynamics requires prospective evaluation., (© 2019 Wiley Periodicals, Inc.)

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., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objective: To define the technique of estimating ductal diameter (DD) that best correlates with echocardiographic markers of transductal shunt volume in preterm infants >7 days old with persistent patent ductus arteriosus (PDA)., Study Design: We conducted a retrospective study of 104 neonates born at <30 weeks gestation that had targeted neonatal echocardiography evaluation of PDA performed between 7 and 30 days. We used univariate analysis to determine the association of echocardiographic markers of shunt volume with ductal size definitions: DD, DD indexed to weight, and DD indexed to left pulmonary artery diameter., Results: Two hundred echocardiograms were reviewed from 104 patients with a median gestational age of 25.4 weeks (range, 25-26.3 weeks) and a median birth weight of 810 g (range, 740-920 g). We found a weak correlation of each method of PDA size definition with individual echocardiographic markers of transductal shunt volume, of which nonindexed DD demonstrated the best correlation. The best correlation was found with markers of systemic hypoperfusion, such as diastolic flow reversal in the descending aorta (R 2 = 0.24) and celiac artery (R 2 = 0.21). Markers of pulmonary overcirculation, such as left ventricular end-diastolic diameter (R 2 = 0.19) and left ventricular output (R 2 = 0.17), showed fair correlation with nonindexed DD., Conclusion: In preterm infants >7 days old with PDA, nonindexed DD demonstrated weak correlations with individual echocardiographic markers of shunt volume. These data highlight the need for comprehensive echocardiographic evaluation in addition to diameter measurements to provide a better understanding of the hemodynamic consequences of PDA., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the utilization and study the factors associated with the impact on clinical management of a new TNE consultation service in a perinatal center., Methods: This retrospective cohort study included all neonates who underwent TNE consultation at the neonatal unit of Mount Sinai Hospital in Toronto, Canada (November 2011 and July 2015). The consults that had "impact" were defined as those that led to a TNE suggested change in the clinical management within 6 h of its recommendation. Logistic regression analysis was performed to identify factors associated with a change in clinical management following the consultation., Results: A total of 553 consults were performed for 268 infants (gestational age: 27 ± 4 weeks and age at initial consult: 16 (5, 34) days). Patent ductus arteriosus (PDA, 61%), suspected pulmonary hypertension (PH, 27%), and systemic hypotension (SH, 9%) were the common indications. The average consultations increased from 9 in 2012-2013 to 20 per month in 2014-2015. Forty eight percent of consults had an impact on clinical management (PDA scans: 38%, PH: 58%, and SH: 81%, p < 0.01 between all). Male gender (adjusted odds ratio (95% confidence interval): 1.9 (1.0, 3.5); p = 0.04), mechanical ventilation (2.43 (1.2, 4.9); p = 0.01), and scans for PH (7.1 (2.2, 23.2); p < 0.01) and SH (2.6 (1.1, 6.5); p = 0.03) were independently associated with the impact on clinical management. TNE consults identified all incidental cases of major structural defects (n = 4), and six out of ten minor diagnoses., Conclusions: TNE consult service demonstrated an increasing utilization and a significant impact on clinical management over time especially for non-PDA indications and in situations of high-illness severity. Although, all major cardiac defects were identified, some minor congenital defects were missed by TNEs.

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., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Focused cardiac sonography and targeted neonatal echocardiography refer to goal-directed cardiac imaging using ultrasound, typically by noncardiologic specialists. Although the former consists of a rapid qualitative assessment of cardiac function, which is usually performed by acute care practitioners, the latter refers to detailed functional echocardiography to obtain quantitative and qualitative indexes of pulmonary and systemic hemodynamics in sick neonates and is typically performed by neonatologists. Although the use of these modalities is increasing, they still remain unavailable in most North American centers providing acute care to neonates, partly because of limited data regarding their direct impact on patient care. Here we present a series of 5 cases from a large perinatal unit in which immediate availability of relevant expertise led to important and arguably life-saving clinical interventions. In 4 of these cases, focused cardiac sonography was sufficient to make the diagnosis, whereas in 1 case, clinical integration of detailed systemic hemodynamics measured on target neonatal echocardiography was required.

Objective: To compare the effect of oral glucose given with or without facilitated tucking (FT), versus placebo (water) to facilitate image acquisition during a targeted neonatal echocardiography (TNE)., Design: Factorial, double blind, randomized controlled trial., Setting: Tertiary neonatal intensive care unit (NICU)., Patients: Infants born between 26 and 42 weeks of gestation (GA)., Interventions: One of four treatment groups: oral water (placebo), oral glucose (25%), facilitated tucking with oral water or facilitated tucking with oral glucose, during a single, structured TNE. All infants received a soother., Main Outcome Measure: Change in Behavioral Indicators of Infant Pain (BIIP) scores., Results: 104 preterm infants were randomized (mean ± SD GA: 33.4 ± 3.5 weeks). BIIP scores remained low during the echocardiography scan (median, [IQ range]: 0, [0 to 1]). There were no differences in the level of agitation of infants amongst the treatment groups, with estimated reductions in mean BIIP relative to control of 0.27 (95%CI -0.40 to 0.94) with use of oral glucose and .04 (-0.63 to 0.70) with facilitated tucking. There were also no differences between treatment groups in the quality and duration of the echocardiography scans., Conclusions: In stable infants in the NICU, a TNE can be performed with minimal disruption in a majority of cases, simply by providing a soother. The use of 25% glucose water in this context did not provide further benefit in reducing agitation and improving image acquisition., Clinical Trial Registration: Clinical Trials.gov: NCT01253889.

Background: There is a paucity of echocardiographic data describing right ventricular (RV) dimensions and function in the early transitional newborn period., Methods: Fifty healthy term newborns underwent serial echocardiography at a mean of 15 ± 2 and 35 ± 2 hours of age. RV dimensions and functional indices were measured as recommended in the American Society of Echocardiography's recent guidelines. Additional novel parameters included RV anteroinferior basal diameter, fractional area change (FAC) from the apical three-chamber view, and speckle-tracking echocardiography-derived peak longitudinal strain in the RV lateral (apical four-chamber view) and inferior (apical three-chamber view) walls. Results obtained at both time points were compared., Results: Linear dimensions and tissue Doppler velocities were highly reproducible, while time intervals and FAC measurements were more variable. Three-chamber FAC was higher than four-chamber FAC (36 ± 5% vs. 24 ± 7%, P < .001). Lateral wall peak longitudinal strain was similar to the value for the inferior wall (22 ± 4% vs 18 ± 5%, P > .05). A small increase in RV dimensions was noted on day 2 of life (midcavity diameter, 1.71 ± 0.19 vs 1.55 ± 0.19 cm, P < .01; RV anteroinferior basal diameter, 2.24 ± 0.29 vs 2.06 ± 0.24 cm, P < .01; end-diastolic-area in the apical four-chamber view, 4.32 ± 0.64 vs 4.10 ± 0.69 cm(2), P = .04), while no changes occurred in functional indices. RV dimensions and FAC showed moderate linear correlations with birth weight. Z scores could be computed for the majority of measured indices., Conclusions: Using conventional and novel indices, the investigators describe a comprehensive echocardiographic protocol for neonatal RV imaging, establish reference ranges, and describe the effect of physiologic postnatal transition on RV dimensions and function. This will facilitate future investigations of RV dysfunction in neonatal cardiopulmonary disorders., (Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

The use of plain radiographs in assessing the correct position of peripherally inserted central catheter (PICC) line tips is not always accurate. Ultrasound may be a better modality in detecting tip position and aid in line manipulation. We assessed the accuracy of plain radiographs in determining PICC line tip position compared with using targeted neonatal echocardiography (TnECHO) in a tertiary neonatal intensive care unit. Following PICC insertion, tip position was confirmed using TnECHO after the first radiograph. A 2 × 2 table was constructed to compare the two modalities' ability to detect line position. A total of 22 infants were included in the study with a gestation of 26.5 weeks (25.4 to 28.8) and birth weight of 833 g (710 to 1930). Concordance between radiographs and TnECHO for PICC line tip position occurred in 13 infants (59%). Sensitivity of radiographs in determining malposition was 64% with a specificity of 55%. Three infants were incorrectly identified to have deep lines and two infants were incorrectly identified to have short lines. In nine infants (41%), a second radiograph was avoided following line manipulation using TnECHO. TnECHO is a useful tool in identifying tip position, performing real-time manipulation, and minimizing exposure to further radiographs., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective An alternative therapy for preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA) is needed when cyclooxygenase inhibitors fail or where treatment is contraindicated due to coexisting renal failure, necrotizing enterocolitis, and/or intestinal perforation. No studies have evaluated the efficacy of per rectum (PR) acetaminophen. The study aimed to evaluate the efficacy of PR acetaminophen in modulating the risk of PDA ligation. Study Design A retrospective matched case–control study was conducted to compare neonates born <29 weeks' gestation with evidence of hsDA, in an era when rescue rectal acetaminophen was used (January 2014–March 2018) as a treatment strategy, versus historical controls (July 2006–August 2012). All patients underwent comprehensive echocardiography assessment of ductal shunt volume according to a standardized protocol. Acetaminophen treated neonates were matched according to demographics, gestation, preintervention echocardiography features, and comorbidities. Control patients were selected when an echocardiography was performed at an equivalent postnatal age. Infants with a genetic syndrome, severe congenital malformation, or major forms of congenital heart disease excluding small atrial septal defect or ventricular septal defect, PDA, or patent formale ovale were excluded. The primary outcome was surgical ligation of the PDA. Secondary outcomes included echocardiography indices of hemodynamic significance, the composite of death, or severe BPD (defined by ventilator dependence at 36 weeks postmenstrual age). Descriptive statistics and univariate (t -tests, Fisher's exact test, and Mann–Whitney U test) analyses were used to evaluate clinical and echocardiography characteristics of the groups and compare outcomes. Results Forty infants (20 cases and 20 controls), with similar demographic and echocardiography features, were compared. Cases received 6.8 ± 0.7 days (60 mg/kg/day) of PR acetaminophen. Responders (n = 12, 60%) had echocardiography evidence of reduced ductal diameter (2.2 mm [1.9–2.6] to 1.1 mm [0–1.7], p = 0.002), left ventricular output (363 ± 108–249 ± 61 mL/min/kg; p = 0.002) and left atrium to aortic root ratio (1.7 ± 0.3–1.3 ± 0.2; p = 0.002) following treatment. The rate of PDA ligation was 50% lower (p = 0.02) and composite outcome of death or severe bronchopulmonary dysplasia was reduced (p = 0.04) in the acetaminophen group. Conclusion Rectal acetaminophen was associated with improvement in echocardiography indices of PDA shunt volume, a 50% reduction in PDA ligation rates and a reduction in the composite outcome of death or severe BPD. Pharmacologic and further prospective clinical studies are needed. Key Points Many preterm infants encounter the clinical consequences of a hemodynamically significant PDA. The merits and optimal timing of PDA ligation remains an area of controversy amongst neonatologists. Cyclooxygenase inhibitors are associated with adverse events or are often contraindicated. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the relationship of echocardiographic markers of left heart overload and flow in peripheral major end‐organ vessels (eg, celiac artery) with the presence of reversed holodiastolic flow in the descending aorta, considered a surrogate marker of an increased transductal shunt volume, in preterm patients with a patent ductus arteriosus (PDA). Methods: This work was a retrospective study of data from echocardiography performed to investigate the hemodynamic significance of a PDA in preterm patients. We studied differences in echocardiographic markers of the PDA shunt volume according to patterns of flow in the postductal descending aorta (no PDA, PDA with antegrade diastolic flow, and PDA with reversed diastolic flow). The strength of the association between each echocardiographic marker and the presence of aortic holodiastolic flow reversal was investigated. Results: We studied 137 patients with a median (interquartile range) birth weight of 850 (694–1030) g and a median gestational age of 25 (24–27) weeks. Among patients with a PDA (113), those with diastolic flow reversal in the descending aorta (44) presented had increased echocardiographic markers representative of the shunt volume (increased left ventricular output, left atrial‐to‐aortic ratio, pulmonary vein D wave, and shorter isovolumic relaxation time) compared to those with aortic antegrade diastolic flow. A positive, albeit weak, correlation between diastolic flow reversal and shunt volume echocardiographic markers was found. Abnormal diastolic flow in the celiac artery had the strongest correlation (R2 = 0.24). Conclusions: In preterm patients with a PDA, echocardiographic markers of the shunt volume were more abnormal in patients with reversed diastolic flow in the descending aorta. These data support the assumption that variance in these markers are related to the shunt volume, which needs consideration when adjudicating hemodynamic significance. [ABSTRACT FROM AUTHOR]

Background: Characteristic changes in cerebral saturation (CrSO2), amplitude-integrated electroencephalography (aEEG), and echocardiography (ECHO) may be associated with intraventricular hemorrhage (IVH); however, the feasibility of their combined application is not known. Objective: The aim of this work was to investigate the feasibility and safety of combined multimodal cerebral and hemodynamic monitoring in extremely low gestational age (ELGA) infants in the first 72 h after birth. Methods: In this prospective -observational study of 50 infants born between 23 + 0 and 27 + 6 weeks gestation, we measured CrSO2 and aEEG, starting <8 h until 72 h of age. Sequential echocardiography and head ultrasound were performed at 4–8, 12–18, 24–30, and 48–60 h of age. The primary outcome was feasibility of multimodal monitoring, defined as >75% of the subjects satisfying at least 3/4 criteria: (a) CrSO2 and (b) aEEG monitoring each for >75% of the time, and (c) at least 2 out of 4 ECHO and (d) head ultrasounds (at least one by age 24 h). Adverse reactions to sensors, desaturation, and bradycardia during ultrasound studies were recorded. Results: Fifty infants were enrolled over 14 months. Multimodal monitoring was feasible in 49 (98%) infants. Forty-one (82%) infants fulfilled all 4 criteria. Mild erythema below CrSO2 sensors lasting 3–8 h without skin breakdown was noted in 8/50 subjects (16%). Desaturation was noted during 17/197 (8.6%) of the ultrasound studies. In total, 26/50 (52%) infants developed IVH (grade I/II, n = 22; grade III/IV, n = 4). Conclusion: Multimodal monitoring is feasible, safe, and well tolerated in ELGA infants in the first 72 h after birth. [ABSTRACT FROM AUTHOR]

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Objective This article compares hemodynamic characteristics of neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) with normal versus abnormal brain magnetic resonance imaging (MRI). Methods Serial echocardiography (echo) was performed within 24 hours, after 48 to 72 hours of cooling, within 24 hours of normothermia, and after starting feeds. Pulmonary hemodynamics, cardiac output, and ventricular function were evaluated. All neonates underwent brain MRI (day 4-5), per clinical standard of care. Clinical cardiovascular and echocardiography characteristics were compared between patients with normal versus abnormal MRI. Cardiovascular changes during TH and after rewarming were identified. Results Twenty neonates at median gestation and birth weight of 40 weeks (inter-quartile range [IQR]: 39, 41) and 3,410 g (IQR: 2,885, 4,093), respectively, were enrolled. Increased median left ventricular output (LVO) (106-159 mL/kg/min, p < 0.001) and reduced isovolumic relaxation time (IVRT) (48-42 ms, p < 0.001) were seen after rewarming. Echocardiography evidence of pulmonary hypertension (PH) was identified in five neonates. Eight neonates (40%) had brain injury identified on MRI (watershed [n = 4], basal ganglia [n = 4]); this subgroup were more likely to have echo evidence of PH at 24 hours. Conclusion Longitudinal changes in cardiac output were noted in neonates with HIE during TH and rewarming. Echocardiography evidence of PH, however, was associated with abnormal MRI brain. The prognostic relevance of these physiologic changes requires more comprehensive delineation. [ABSTRACT FROM AUTHOR]

Background: Failure of first course of indomethacin (FCI) for patent ductus arteriosus (PDA) treatment in preterm neonates often prompts clinicians to consider a second course (SCI).Objective: To identify factors including baseline characteristics and response to FCI that are associated with non-response to SCI for PDA treatment in preterm neonates.Methods: In this retrospective observational study, neonates ≤32 weeks admitted to a tertiary NICU over 5 years who received two indomethacin courses for PDA treatment were reviewed. Only neonates with echocardiograms (ECHO) immediately before and after receipt of each indomethacin course were included. Primary outcome was non-response to SCI. Baseline characteristics and response to FCI were compared between responders and non-responders of SCI.Results: Of the 98 neonates enrolled, 47 (48%) had non-response to SCI. Of them, 27 patients (57%) had prior non-response to FCI, while of the 51 neonates who responded to SCI, 24 neonates (47%) had prior non-response to FCI. The adjusted risk of non-response to SCI in patients who had non-response to FCI was 37% higher (relative risk = 1.37, 95%CI: 0.87-1.80; p = .07) compared to those who had response to FCI. Multivariable analysis showed that increasing gestational age (AOR: 1.6, 95%CI: 1.1-2.3, p = .03) was associated with a higher odds of non-response to SCI while the odds of non-response to SCI increased by 90% in patients with non-response to FCI (AOR: 1.9, 95%CI: 0.8-4.5; p = .15) compared to those with success of FCI, although no statistical significance was observed.Conclusions: Advanced gestational age was the predictor of non-response to SCI in preterm neonates. [ABSTRACT FROM AUTHOR]

Chronic neonatal pulmonary hypertension (PHT) frequently results in early death. Systemically administered Rho-kinase (ROCK) inhibitors prevent and reverse chronic PHT in neonatal rats, but at the cost of severe adverse effects, including systemic hypotension and growth restriction. Simvastatin has pleiotropic inhibitory effects on isoprenoid intermediates that may limit activity of RhoA, which signals upstream of ROCK. We therefore hypothesized that statin treatment would safely limit pulmonary vascular RhoA activity and prevent and reverse experimental chronic neonatal PHT via downstream inhibitory effects on pathological ROCK activity. Sprague-Dawley rats in normoxia (room air) or moderate normobaric hypoxia (13% O2) received simvastatin (2 mg·kg-1 ·day-1 ip) or vehicle from postnatal days 1–14 (prevention protocol) or from days 14 –21 (rescue protocol). Chronic hypoxia increased RhoA and ROCK activity in lung tissue. Simvastatin reduced lung content of the isoprenoid intermediate farnesyl pyrophosphate and decreased RhoA/ROCK signaling in the hypoxiaexposed lung. Preventive or rescue treatment of chronic hypoxiaexposed animals with simvastatin decreased pulmonary vascular resistance, right ventricular hypertrophy, and pulmonary arterial remodeling. Preventive simvastatin treatment improved weight gain, did not lower systemic blood pressure, and did not cause apparent toxic effects on skeletal muscle, liver or brain. Rescue therapy with simvastatin improved exercise capacity. We conclude that simvastatin limits RhoA/ROCK activity in the chronic hypoxia-exposed lung, thus preventing or ameliorating hemodynamic and structural markers of chronic PHT and improving long-term outcome, without causing adverse effects. [ABSTRACT FROM AUTHOR]

Summary Persistent pulmonary hypertension of the newborn (PPHN) is a frequent cause for admission to the neonatal intensive care unit and is associated with mortality and variable morbidities. It is primarily a state of oxygenation failure representing a failure of the normal postnatal decline in pulmonary vascular resistance that may be associated with right ventricular dysfunction. Enhanced knowledge of the pathophysiologic contributors to this syndrome helps clinicians understand its phenotypic expression and facilitates more focused intensive care decision-making. The approach to treatment should be based on alleviation of the elevation in pulmonary vascular resistance and should include optimization of lung recruitment and judicious use of pulmonary vasodilators. When response to inhaled nitric oxide is suboptimal, the physiologic contributors to impaired oxygenation need further investigation. Targeted neonatal echocardiography provides novel physiologic insights; in particular, it may help assess the adequacy of right ventricular performance, the relative contribution of the fetal shunts and the magnitude of the overall impairment to cardiac output. This information may facilitate therapeutic next steps and whether adjunctive vasodilators or drugs to augment ventricular function are preferable. This article provides a comprehensive overview of the pathological contributors to PPHN, the physiologic constituents of its phenotypic expression, standard approach to therapeutic intervention, and the role of bedside echocardiography in enhancing the decision-making process. [ABSTRACT FROM AUTHOR]

Background: Non-invasive cardiac output monitoring (NICOM; NICOM™) may be useful in the management of extremely premature preterm infants. Objectives: To evaluate a new bioreactance-based method of continuous NICOM in preterm infants following patent ductus arteriosus (PDA) ligation. Methods: Infants underwent three paired NICOM and echocardiography assessments of stroke volume (SV) and left ventricular output (LVO) in the postoperative period: at 1, 6-8, and 16-18 h postoperatively. NICOM- and echocardiography-measured SV and LVO during those periods were compared using Bland-Altman analysis and the intraclass correlation coefficient (ICC). Results: Twenty-five infants with a median (interquartile range) gestational age and birth weight of 25.0 weeks (24.5-25.9) and 700 g (615-775), respectively, were included. The overall systematic bias (limits of agreement) across all time points between the NICOM and echocardiography SV readings was 39% (8-69) with NICOM consistently underestimating echocardiography values. There was moderate consistency between NICOM and echocardiography SV values (ICC 0.78, p < 0.001). Compared with the 1-hour scans, the 6- to 8- and 16- to 18-hour scans had increased biases of 7.9% (95% CI 2.5-13.2) and 9.7% (95% CI 3.6-15.8), respectively. Conclusion: Continuous LVO measurement using NICOM was feasible and demonstrated a consistent systematic bias compared with echocardiography in unstable extremely preterm infants without a PDA ligation. NICOM may be used as a trending tool for continuous monitoring in this population, but wide limits of agreement and increasing bias over time suggest it is not interchangeable with echocardiography. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: Non-invasive cardiac output monitoring is a potentially useful clinical tool in the neonatal setting. Our aim was to evaluate a new method of non-invasive continuous cardiac output (CO) measurement (NICOM™) based on the principle of bioreactance in neonates. Methods: In this prospective observational study, 10 neonates underwent 97 paired NICOM and echocardiography (echo) assessments of left ventricular output (LVO). For each neonate, NICOM measurements of left ventricular stroke volume (SV) and LVO over a 2- to 4-hour period were correlated with blinded, simultaneous, discrete echo measurements of SV and LVO. The precision and accuracy of the NICOM monitor relative to echo during periods of steady state were assessed. Results: The infants' median birth weight was 2.72 kg (IQR 1.56-3.23 kg, range 1.44-4.00) and their median gestation was 37 weeks (IQR 31-40 weeks, range 31-41). Median NICOM SV and LVO readings were consistently lower than echo (2.6 ml [IQR 1.4-3.2, range 0.6-5.3] vs. 3.5 ml [IQR 2.1-4.4, range 1.1-6.8], and 400 ml/min [IQR 233-476] vs. 559 ml/min [IQR 386-652], p < 0.001). The NICOM LVO readings were lower than the echo readings by a mean of 153 ± 56 ml/kg. NICOM consistently under-read LVO by 31 ± 8%, and this systematic difference was constant across the range of LVOs obtained. There was a strong correlation between NICOM and echo measurements of LVO (r = 0.95, p < 0.001). Conclusion: Non-invasive cardiac output monitoring is feasible in neonates. Further validation studies in neonatal animal experimental models and human neonates need to be conducted before routine clinical use. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Right ventricular dysfunction, typically qualitatively diagnosed (Q-RVd) in preterm infants, requires echocardiography which is not always acutely available. We aimed to identify clinical indices of Q-RVd in very preterm infants (gestational age, GA <32 weeks) with persistent pulmonary hypertension of newborn (PPHN) and examine the reliability and validity of Q-RVd. Forty-seven infants with mean ± SD GA of 26.8 ± 2.7 weeks who had targeted neonatal echocardiography (TNE) ≤ 72 h old, during PPHN, were retrospectively studied. Three standard TNE clips were reviewed by two blinded assessors, and infants categorized as Q-RVd if moderate-severe RVd was diagnosed on ≥2 clips. Cardiopulmonary clinical indices at TNE and quantitative RV functional markers were compared between Q-RVd vs. no-RVd groups. Potential quantitative RVd definitions examined by classifying each measurement as "low" or "normal" using published data. Inter-rater agreement for Q-RVd assessed using Kappa statistics. Mean age at TNE was 25.3 ± 20.4 h with Q-RVd diagnosed in 19(40 %) infants. Q-RVd group demonstrated higher peak oxygen requirements (96 ± 9 % vs. 84 ± 16 %, p < 0.01); however, no clinical parameters at TNE differentiated the groups. Quantitative measures were lower in Q-RVd patients, confirming classification validity. Among tested quantitative definitions, low RV stroke volume was associated with lower systolic blood pressure (41 ± 7 vs. 47 ± 9 mmHg, p = 0.02) and higher shock index (4.02 ± 0.80 vs. 3.44 ± 0.72, p = 0.02). Kappa for Q-RVd was 0.55 (95%CI 0.32–0.77). The non-specific nature of clinical markers of RVd in preterm infants with PPHN necessitates echocardiographic diagnosis of RVd. Studies should examine prognostic relevance of RVd and establish outcome-based quantitative definitions in preterm infants. • Right ventricular dysfunction (RVd) is difficult to detect clinically in preterms. • Study supports use of timely echocardiography in preterm pulmonary hypertension. • Qualitative RVd diagnosis may be valid but is only moderately reliable in preterms. • Qualitative method may over-diagnose RVd in preterm pulmonary hypertension. • Normative dataset of quantitative echocardiography measures in preterms is needed. [ABSTRACT FROM AUTHOR]