Comprehensive Evaluation of Right Heart Performance and Pulmonary Hemodynamics in Neonatal Pulmonary Hypertension: Evaluation of cardiopulmonary performance in neonatal pulmonary hypertension

Purpose of review: Pulmonary hypertension is characterized by an elevation of pulmonary artery pressures and prolonged exposure of the right ventricle to high afterload that collectively contribute to morbidity and mortality in both the term and preterm infants. This review summarizes the pathogenesis, etiologies, and hemodynamic profiles of the conditions that result in pulmonary hypertension in neonates. We explore the application of echocardiographic techniques for the assessment of right ventricular performance and pulmonary hemodynamics that enhance and guide the diagnosis and management strategies in neonates. Recent findings: Clinical assessments based on the determinants of mean pulmonary artery pressures (pulmonary vascular resistance, pulmonary blood flow, and pulmonary capillary wedge pressure) provide a physiologic approach in determining the acute and chronic etiologies of pulmonary hypertension in neonates. In addition, advances in neonatal echocardiography now afford the capability to obtain quantitative information that often precedes the qualitative information acquired by conventional methods and also provide sensitive markers of right ventricle performance for prognostic information based on the determinants of mean pulmonary artery pressures. Summary: Neonatal pulmonary hypertension represents a physiologic spectrum that accounts for the variance in clinical presentation and response to therapies. Physiology-based approaches to etiological identification, coupled with the emerging echocardiographic methods for the assessment of pulmonary hypertension in neonates will likely help to identify cardiovascular compromise earlier, guide therapeutic intervention, monitor therapeutic effectiveness, and improve overall outcome

Circulatory Insufficiency and Hypotension Related to the Ductus Arteriosus in Neonates

The biological role of the ductus arteriosus (DA) in neonates varies from an innocent bystander role during normal postnatal transition, to a supportive role when there is compromise to either systemic or pulmonary blood flow, to a pathological state in the presence of hemodynamically significant systemic to pulmonary shunts, as occurs in low birth weight infants. Among a wide array of clinical manifestations arising due to the ductal entity, systemic circulatory insufficiency and hypotension are of significant concern as they are particularly challenging to manage. An understanding of the physiologic interplay between the DA and the circulatory system is the key to developing appropriate targeted therapeutic strategies. In this review, we discuss the relationship of systemic hypotension to the DA, emphasizing the importance of critical thinking and a precise individual approach to intensive care support. We particularly focus on the variable states of hypotension arising directly due to a hemodynamically significant DA or seen in the period following successful surgical ligation. In addition, we explore the mechanistic contributions of the ductus to circulatory insufficiency that may manifest during the transitional period, states of maladapted transition (such as acute pulmonary hypertension of the newborn), and congenital heart disease (both ductal dependent and non-ductal dependent lesions). Understanding the dynamic modulator role of the ductus according to the ambient physiology enables a more precise approach to management. We review the pathophysiology, clinical manifestations, diagnosis, monitoring, and therapeutic intervention for the spectrum of DA-related circulatory compromise

Left ventricle phenotyping utilizing tissue doppler imaging in premature infants with varying severity of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is characterized by alveolar-capillary simplification and is associated with pulmonary hypertension (PH) in preterm infants. The contribution of left ventricle (LV) disease towards this severe BPD-PH phenotype is not well established. We aimed to describe the longitudinal trajectory of the LV function as measured by tissue Doppler imaging (TDI) and its association with BPD-PH. We retrospectively assessed prospectively acquired clinical and echocardiographic data from 77 preterm infants born between 2011 and 2013. We characterized the LV function by measuring systolic and diastolic myocardial velocities (s\u27, e\u27, a\u27), isovolumetric relaxation time (IVRT), and myocardial performance index with TDI at three time periods from 32 and 36 weeks, postmenstrual age through one year of age. We also measured post systolic motion (PSM), a marker of myocardial dysfunction that results from asynchronous movement of the ventricular walls, and not previously described in preterm infants. Patients were stratified into groups according to BPD severity and the presence of PH and compared over time. Conventional TDI measures of the LV function were similar between groups, but the septal PSM was significantly prolonged over the first year of age in patients with BPD-PH. PSM provides a novel objective way to assess the hemodynamic impact of lung and pulmonary vascular disease severity on LV function in preterm infants with BPD and PH

Cardiac performance in the first year of age among preterm infants fed maternal breast milk

Importance: There is a beneficial association between human breast milk exposure in the neonatal period and cardiac mechanics in adults who were born preterm. It is unknown whether this benefit is apparent in infants in the first year of age. Objective: To test the hypothesis that higher consumption of mother\u27s own milk in preterm infants is associated with enhanced cardiac performance during the first year of age. Design, Setting, and Participants: This cross-sectional study of cardiac and nutritional data at an academic medical center included 80 individuals born preterm and 100 individuals in the control group born full-term. All births were between 2011 and 2013. Two-dimensional echocardiograms were performed at 32 weeks\u27 and 36 weeks\u27 postmenstrual age and at 1 year\u27s corrected age in individuals born preterm and at 1 month and 1 year of age in individuals born full-term. Statistical analysis was performed from January to May 2021. Exposures: Consumption of mother\u27s own milk. Main Outcomes and Measures: Main study outcomes included echocardiography measures of right and left ventricle longitudinal strain (function), left ventricle mass index and right ventricular areas (morphology), and pulmonary vascular resistance (pulmonary hemodynamics) at age 1 year. Results: Of 180 infants included in the study, 97 (54%) were Black infants and 89 (49%) were female infants. Among the 80 infants born in the preterm cohort, 43 (54%) were female infants and 43 (54%) were Black infants. The median gestational age at birth of the preterm infants was 27.0 weeks (interquartile range, 26.0-28.0 weeks) and the median birth weight was 960 g (interquartile range, 800-1138). For each week of exposure to mother\u27s own milk, preterm infants had greater magnitudes of right ventricular strain (eg, right longitudinal strain: β, 0.021; 95% CI, 0.002-0.041; P \u3c .001) and left ventricular strain (eg, left longitudinal strain: β, 0.065; 95% CI, 0.049-0.080; P = .01), larger right ventricle areas (eg, systolic area: β, 0.026; 95% CI, 0.011-0.042; P = .009), larger left ventricle mass index (β, 0.045; 95% CI, 0.024-0.073; P = .003), and decreased pulmonary vascular resistance (eg, pulmonary artery acceleration time: β, 0.041; 95% CI, 0.018-0.063; P \u3c .001) at 1 year\u27s corrected age, even after accounting for gestational age and common neonatal morbidities. Cardiac values approached those seen in controls born full-term with increased mother\u27s own milk exposure. There were no differences in any of the cardiac indices at 32 weeks\u27 postmenstrual age, but with each week of exposure, right ventricle function (eg, right longitudinal strain: β, 0.016; 95% CI, 0.002-0.031; P \u3c .001) was greater and pulmonary pressured (eg, pulmonary artery acceleration time: β, 0.0032; 95% CI, 0.0013-0.0062; P \u3c .001). Conclusions and Relevance: This study found that preterm infants with higher consumption of mother\u27s own milk had enhanced cardiac performance at age 1 year, suggesting that mother\u27s own milk consumption may play a dynamic modulator role on cardiac mechanics in preterm-born infants and help in normalization of the preterm cardiac phenotype

Maturational patterns of left ventricular rotational mechanics in pre-term infants through 1 year of age

BACKGROUND: Pre-mature birth impacts left ventricular development, predisposing this population to long-term cardiovascular risk. The aims of this study were to investigate maturational changes in rotational properties from the neonatal period through 1 year of age and to discern the impact of cardiopulmonary complications of pre-maturity on these measures. METHODS: Pre-term infants (\u3c29 weeks at birth, n = 117) were prospectively enrolled and followed to 1-year corrected age. Left ventricular basal and apical rotation, twist, and torsion were measured by two-dimensional speckle-tracking echocardiography and analysed at 32 and 36 weeks post-menstrual age and 1-year corrected age. A mixed random effects model with repeated measures analysis was used to compare rotational mechanics over time. Torsion was compared in infants with and without complications of cardiopulmonary diseases of pre-maturity, specifically bronchopulmonary dysplasia, pulmonary hypertension, and patent ductus arteriosus. RESULTS: Torsion decreased from 32 weeks post-menstrual age to 1-year corrected age in all pre-term infants (p \u3c 0.001). The decline from 32 to 36 weeks post-menstrual age was more pronounced in infants with cardiopulmonary complications, but was similar to healthy pre-term infants from 36 weeks post-menstrual age to 1-year corrected age. The decline was due to directional and magnitude changes in apical rotation over time (p \u3c 0.05). CONCLUSION: This study tracks maturational patterns of rotational mechanics in pre-term infants and reveals torsion declines from the neonatal period through 1 year. Cardiopulmonary diseases of pre-maturity may negatively impact rotational mechanics during the neonatal period, but the myocardium recovers by 1-year corrected age

Markers of Maternal and Infant Metabolism are Associated with Ventricular Dysfunction in Infants of Obese Women with Type 2 Diabetes

BACKGROUND To test the hypothesis that infants born to obese women with pregestational type 2 diabetes mellitus (IBDM) have ventricular dysfunction at one month that is associated with markers of maternal lipid and glucose metabolism. METHODS In a prospective observational study of IBDM (OB+DM, n=25), echocardiography measures of septal, left (LV) and right ventricular (RV) function and structure were compared at one month of age to infants born to OB mothers without DM (OB, n=24), and non-OB without DM (Lean, n=23). Basal maternal lipid and glucose kinetics and maternal plasma and infant (cord) plasma were collected for hormone and cytokine analyses. RESULTS RV, LV, and septal strain measures were lower in the OB+DM infants vs. other groups, without evidence of septal hypertrophy. Maternal hepatic insulin sensitivity, maternal plasma free fatty acid concentration, and cord plasma insulin and leptin most strongly predicted decreased septal strain in the OB+DM infants. CONCLUSION IBDM’s have reduced septal function at one month in the absence of septal hypertrophy, which is associated with altered maternal and infant lipid and glucose metabolism. These findings suggest that maternal obesity and DM may have a prolonged impact on the cardiovascular health of their offspring, despite resolution of cardiac hypertrophy

Pulmonary Artery Acceleration Time Provides a Reliable Estimate of Invasive Pulmonary Hemodynamics in Children

Background Pulmonary artery acceleration time (PAAT) is a non-invasive method to assess pulmonary hemodynamics, but lacks validity in children. This study sought to evaluate the accuracy of Doppler echocardiography (DE) derived PAAT in predicting right heart catheterization (RHC) derived pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR) and compliance in children. Methods Prospectively acquired and retrospectively measured DE derived PAAT and RHC derived systolic PAP (sPAP), mean PAP (mPAP), index PVR (PVRi) and compliance were compared by regression analysis in a derivation cohort of 75 children (median age, 5.3 years; 1.3–12.6) with wide ranges of pulmonary hemodynamics. To account for heart rate variability, PAAT was adjusted for right ventricle ejection time (RVET) and corrected by the RR interval. Regression equations incorporating PAAT and PAAT:RVET from the derivation cohort were then evaluated for the accuracy of its predictive values for invasive pulmonary hemodynamics in a validation cohort of 50 age- and weight- matched children with elevated PAP and PVR. Results There were significant inverse correlations between PAAT and RHC derived mPAP (r = −0.82) and PVRi (r= −0.78) and direct correlation (r= 0.78) between PAAT and pulmonary compliance in the derivation cohort. For detection of pulmonary hypertension (PRVi > 3 WU x m2 and mPAP > 25 mmHg), PAAT < 90 msec and PAAT:RVET < 0.31 resulted in a sensitivity of 97% and a specificity of 95%. In the derivation cohort, the regression equations relating PAAT with mPAP and PVRi were: mPAP = 48 – 0.28 x PAAT and PVRi = 9 –0.07 x PAAT. These PAAT integrated equations predicted RHC measured pulmonary hemodynamics in the validation cohort with good correlations (r = 0.88, 0.83 respectively), small biases (<10%), and minimal coefficient of variation (<8%). Conclusions PAAT inversely correlates with RHC measured pulmonary hemodynamics and directly correlates with pulmonary arterial compliance in children. The study established PAAT based regression equations in children to accurately predict RHC derived PAP and PVR

Reference Ranges of Left Ventricular Strain Measures by Two-Dimensional Speckle-Tracking Echocardiography in Children: A Systematic Review and Meta-Analysis

BACKGROUND: Establishment of the range of reference values and associated variations of two-dimensional speckle-tracking echocardiography (2DSTE)-derived left ventricular (LV) strain is a prerequisite for its routine clinical adoption in pediatrics. The aims of this study were to perform a meta-analysis of normal ranges of LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) measurements derived by 2DSTE in children and to identify confounding factors that may contribute to variance in reported measures. METHODS: A systematic review was launched in MEDLINE, Embase, Scopus, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library. Search hedges were created to cover the concepts of pediatrics, STE, and left-heart ventricle. Two investigators independently identified and included studies if they reported 2DSTE-derived LV GLS, GCS, or GRS. The weighted mean was estimated by using random effects models with 95% CIs, heterogeneity was assessed using the Cochran Q statistic and the inconsistency index (I(2)), and publication bias was evaluated using the Egger test. Effects of demographic (age), clinical, and vendor variables were assessed in a metaregression. RESULTS: The search identified 2,325 children from 43 data sets. The reported normal mean values of GLS among the studies varied from -16.7% to -23.6% (mean, -20.2%; 95% CI, -19.5% to -20.8%), GCS varied from -12.9% to -31.4% (mean, -22.3%; 95% CI, -19.9% to -24.6%), and GRS varied from 33.9% to 54.5% (mean, 45.2%; 95% CI, 38.3% to 51.7%). Twenty-six studies reported longitudinal strain only from the apical four-chamber view, with a mean of -20.4% (95% CI, -19.8% to -21.7%). Twenty-three studies reported circumferential strain (mean, -20.3%; 95% CI, -19.4% to -21.2%) and radial strain (mean, 46.7%; 95% CI, 42.3% to 51.1%) from the short-axis view at the midventricular level. A significant apex-to-base segmental longitudinal strain gradient (P 94% and P < .001 for each strain measure), which was not explained by age, gender, body surface area, blood pressure, heart rate, frame rate, frame rate/heart rate ratio, tissue-tracking methodology, location of reported strain value along the strain curve, ultrasound equipment, or software. The metaregression showed that these effects were not significant determinants of variations among normal ranges of strain values. There was no evidence of publication bias (P = .40). CONCLUSIONS: This study defines reference values of 2DSTE-derived LV strain in children on the basis of a meta-analysis. In healthy children, mean LV GLS was -20.2% (95% CI, -19.5% to -20.8%), mean GCS was -22.3% (95% CI, -19.9% to -24.6%), and mean GRS was 45.2% (95% CI, 38.3% to 51.7%). LV segmental longitudinal strain has a stable apex-to-base gradient that is preserved throughout maturation. Although variations among different reference ranges in this meta-analysis were not dependent on differences in demographic, clinical, or vendor parameters, age- and vendor-specific referenced ranges were established as well

Application of Neonatologist Performed Echocardiography in the assessment and management of neonatal heart failure unrelated to congenital heart disease

Neonatal heart failure (HF) is a progressive disease caused by cardiovascular and non-cardiovascular abnormalities. The most common cause of neonatal HF is structural congenital heart disease, while neonatal cardiomyopathy represents the most common cause of HF in infants with a structurally normal heart. Neonatal cardiomyopathy is a group of diseases manifesting with various morphological and functional phenotypes that affect the heart muscle and alter cardiac performance at, or soon after birth. The clinical presentation of neonates with cardiomyopathy is varied, as are the possible causes of the condition and the severity of disease presentation. Echocardiography is the selected method of choice for diagnostic evaluation, follow-up and analysis of treatment results for cardiomyopathies in neonates. Advances in neonatal echocardiography now permit a more comprehensive assessment of cardiac performance that could not be previously achieved with conventional imaging. In this review, we discuss the current and emerging echocardiographic techniques that aid in the correct diagnostic and pathophysiological assessment of some of the most common etiologies of HF that occur in neonates with a structurally normal heart and acquired cardiomyopathy and we provide recommendations for using these techniques to optimize the management of neonate with HF

Symptomatic hemorrhage after alteplase therapy not due to silent ischemia

BACKGROUND: Stroke thrombolysis-related intracerebral hemorrhage may occur remotely from the anatomical site of ischemia. One postulated mechanism for this is simultaneous multiple embolization with hemorrhage into a "silent" area of ischemia. RESULTS: A patient suffered a disabling stroke affecting the right cerebral hemisphere. He was treated with intravenous alteplase and underwent extensive early imaging with multimodal MRI. Several hours after treatment he developed a brainstem hemorrhage despite having no evidence of ischemia on DWI MRI in the brainstem. CONCLUSION: Not all occurrences of remote ICH after stroke thrombolysis are secondary to multiple emboli with silent ischemia