Correlating Severity of Pulmonary Hypertension by Echocardiogram with Mortality in Premature Infants with Bronchopulmonary Dysplasia.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth. Infants with BPD are at increased risk for pulmonary hypertension (PH). Cardiac catheterization is the gold standard for diagnosing PH, but cardiac catheterization is challenging to perform in small, sick, premature infants. The utility of echocardiography for diagnosing PH and predicting outcomes in extremely premature infants has not been clearly defined. Therefore, we sought to use predefined criteria to diagnose PH by echocardiogram and relate PH severity to mortality in extremely premature infants with BPD. STUDY DESIGN: Echocardiograms from 46 infants born ≤28 weeks' postmenstrual age with a diagnosis of BPD were assessed for PH by three pediatric cardiologists using predefined criteria, and survival times among categories of PH patients were compared. A total of 458 echocardiograms were reviewed, and 15 (33%) patients were found to have at least moderate PH. Patients with at least moderate PH had similar demographic characteristics to those with no/mild PH. RESULTS: Ninety percent of infants without moderate to severe PH survived to hospital discharge, compared with 67% of infants with at least moderate PH (p = 0.048). Patients with severe PH had decreased survival to hospital discharge (38%) compared with moderate (100%) and no/mild PH (90%) groups. Kaplan-Meier survival curves also differed among PH severity groups (Wilcoxon p < 0.001). CONCLUSION: Using predefined criteria for PH, premature infants with BPD can be stratified into PH severity categories. Patients diagnosed with severe PH by echocardiogram have significantly reduced survival. KEY POINTS: · A composite score definition of PH by echocardiogram showed high inter- and intrarater reliability.. · Infants with severe PH by echocardiogram had decreased survival rates.. · Early diagnosis of PH by echocardiogram dictates treatment which may improve outcomes..

Proteomics discovery in children and young adults with HIV identifies fibrosis, inflammatory, and immune biomarkers associated with myocardial impairment.

People with HIV are at increased risk of cardiac dysfunction; however, limited tools are available to identify patients at highest risk for future cardiac disease. We performed proteomic profiling using plasma samples from children and young adults with perinatally acquired HIV without clinical cardiac disease, comparing samples from participants with and without an abnormal myocardial performance index (MPI). We identified four proteins independently associated with subclinical cardiac dysfunction: ST2, CA1, EN-RAGE, and VSIG2.

Surgical Modulation of Pulmonary Artery Shear Stress: A Patient-Specific CFD Analysis of the Norwood Procedure.

PURPOSR: This study created 3D CFD models of the Norwood procedure for hypoplastic left heart syndrome (HLHS) using standard angiography and echocardiogram data to investigate the impact of shunt characteristics on pulmonary artery (PA) hemodynamics. Leveraging routine clinical data offers advantages such as availability and cost-effectiveness without subjecting patients to additional invasive procedures. METHODS: Patient-specific geometries of the intrathoracic arteries of two Norwood patients were generated from biplane cineangiograms. "Virtual surgery" was then performed to simulate the hemodynamics of alternative PA shunt configurations, including shunt type (modified Blalock-Thomas-Taussig shunt (mBTTS) vs. right ventricle-to-pulmonary artery shunt (RVPAS)), shunt diameter, and pulmonary artery anastomosis angle. Left-right pulmonary flow differential, Qp/Qs, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) were evaluated. RESULTS: There was strong agreement between clinically measured data and CFD model output throughout the patient-specific models. Geometries with a RVPAS tended toward more balanced left-right pulmonary flow, lower Qp/Qs, and greater TAWSS and OSI than models with a mBTTS. For both shunt types, larger shunts resulted in a higher Qp/Qs and higher TAWSS, with minimal effect on OSI. Low TAWSS areas correlated with regions of low flow and changing the PA-shunt anastomosis angle to face toward low TAWSS regions increased TAWSS. CONCLUSION: Excellent correlation between clinically measured and CFD model data shows that 3D CFD models of HLHS Norwood can be developed using standard angiography and echocardiographic data. The CFD analysis also revealed consistent changes in PA TAWSS, flow differential, and OSI as a function of shunt characteristics.

Obesity Predisposes Anthracycline-Treated Survivors of Childhood and Adolescent Cancers to Subclinical Cardiac Dysfunction.

Anthracyclines are effective chemotherapeutics used in approximately 60% of pediatric cancer cases but have a well-documented risk of cardiotoxicity. Existing cardiotoxicity risk calculators do not include cardiovascular risk factors present at the time of diagnosis. The goal of this study is to leverage the advanced sensitivity of strain echocardiography to identify pre-existing risk factors for early subclinical cardiac dysfunction among anthracycline-exposed pediatric patients. We identified 115 pediatric patients with cancer who were treated with an anthracycline between 2013 and 2019. Peak longitudinal left ventricular strain was retroactively calculated on 495 surveillance echocardiograms via the TOMTEC AutoSTRAIN software. Cox proportional hazards models were employed to identify risk factors for abnormal longitudinal strain (> - 16%) following anthracycline treatment. High anthracycline dose (≥ 250 mg/m2 doxorubicin equivalents) and obesity at the time of diagnosis (BMI > 95th percentile-for-age) were both significant predictors of abnormal strain with hazard ratios of 2.79, 95% CI (1.07-7.25), and 3.85, 95% CI (1.42-10.48), respectively. Among pediatric cancer survivors, patients who are obese at the time of diagnosis are at an increased risk of sub-clinical cardiac dysfunction following anthracycline exposure. Future studies should explore the incidence of symptomatic cardiomyopathy 10-15 years post-treatment among patients with early subclinical cardiac dysfunction.

Detection of occult thrombosis in individuals with Fontan circulation by cardiac MRI.

OBJECTIVE: Identifying thrombus formation in Fontan circulation has been highly variable, with reports between 17 and 33%. Initially, thrombus detection was mainly done through echocardiograms. Delayed-enhancement cardiac MRI is emerging as a more effective imaging technique for thrombus identification. This study aims to determine the prevalence of occult cardiac thrombosis in patients undergoing clinically indicated cardiac MRI. METHODS: A retrospective chart review of children and adults in the Duke University Hospital Fontan registry who underwent delayed-enhancement cardiac MRI. Individuals were excluded if they never received a delayed-enhancement cardiac MRI or had insufficient data. Demographic characteristics, native heart anatomy, cardiac MRI measurements, and thromboembolic events were collected for all patients. RESULTS: In total, 119 unique individuals met inclusion criteria with a total of 171 scans. The median age at Fontan procedure was 3 (interquartile range 1, 4) years. The majority of patients had dominant systemic right ventricle. Cardiac function was relatively unchanged from the first cardiac MRI to the third cardiac MRI. While 36.4% had a thrombotic event by history, only 0.5% (1 patient) had an intracardiac thrombus detected by delayed-enhancement cardiac MRI. CONCLUSIONS: Despite previous echocardiographic reports of high prevalence of occult thrombosis in patients with Fontan circulation, we found very low prevalence using delayed-enhancement cardiac MRI. As more individuals are reaching adulthood after requiring early Fontan procedures in childhood, further work is needed to develop thrombus-screening protocols as a part of anticoagulation management.

Guidelines for Performing a Comprehensive Pediatric Transthoracic Echocardiogram: Recommendations From the American Society of Echocardiography.

Echocardiography is a fundamental component of pediatric cardiology, and appropriate indications have been established for its use in the setting of suspected, congenital, or acquired heart disease in children. Since the publication of guidelines for pediatric transthoracic echocardiography in 2006 and 2010, advances in knowledge and technology have expanded the scope of practice beyond the use of traditional modalities such as two-dimensional, M-mode, and Doppler echocardiography to evaluate the cardiac segmental structures and their function. Adjunct modalities such as contrast, three-dimensional, and speckle-tracking echocardiography are now used routinely at many pediatric centers. Guidelines and recommendations for the use of traditional and newer adjunct modalities in children are described in detail in this document. In addition, suggested protocols related to standard operations, infection control, sedation, and quality assurance and improvement are included to provide an organizational structure for centers performing pediatric transthoracic echocardiograms.

Whole-Chest Three-Dimensional Modeling Aids Hybrid Pulmonary Valve Replacement Following Double Switch Operation.

The double switch operation for congenitally corrected transposition of the great arteries (CC-TGA) has been associated with high rates of reintervention, including the need for pulmonary valve replacement. Hybrid interventional approaches can avoid bypass when complex anatomy complicates traditional catheter-based approaches. We present a case of successful transcatheter pulmonary valve replacement via hybrid per-ventricular approach with pre-procedural planning aided by 3D segmentation of skeletal and cardiac anatomy in a patient with surgically corrected CC-GTA.

Three-dimensional modeling of the mitral valve for surgical planning in a pediatric patient: A case-based discussion of the technical challenges of segmentation and printing from 3D transthoracic echocardiographic datasets.

Abnormal atrioventricular valve present great challenges to the surgeon in achieving a successful repair, and thus present a great opportunity for enhanced 3D imaging to guide pre- and intra-operative management. Spatial and temporal resolution of 3D echocardiography enables 3D printing of valve morphology. However, non-linearity, angle dependence, speckle, blur, and resampling complicate segmentation compared to computed tomography (CT) and magnetic resonance imaging (MRI). A case of complex mitral valve disease in a pediatric patient is therefore presented to illustrate the technical challenges of segmentation and 3D printing from echocardiographic data.

ASE Statement on Adapting Pediatric, Fetal, and Congenital Heart Disease Echocardiographic Services to the Evolving COVID-19 Pandemic.

Over the 12 months since the start of the coronavirus disease 2019 pandemic, an explosion of investigation and an increase in experience have led to vast improvement in our knowledge about this disease. However, coronavirus disease 2019 remains a huge public health threat.

A Randomized, Controlled Pharmacokinetic and Pharmacodynamics Trial of Ambrisentan After Fontan Surgery.

OBJECTIVES: To determine the pharmacokinetics, pharmacodynamics, and safety of the hepatically metabolized endothelin receptor antagonist, ambrisentan in children after Fontan surgery. DESIGN: Prospective, randomized, double-blind, placebo-controlled pharmacokinetic/pharmacodynamics and safety trial. SETTING: Single-center, postoperative cardiac ICU. PATIENTS: Children undergoing elective Fontan surgery. INTERVENTIONS: Subjects randomized on postoperative day number 1 to short-term (3 d) treatment with oral ambrisentan (2.5 mg in suspension, daily) versus placebo (4:1 randomization). MEASUREMENTS AND MAIN RESULTS: Plasma drug concentrations were measured at 0.5, 1, 2, 4, and 18-36 hours after the first dose. We developed a population pharmacokinetic model in NONMEM 7.2 (Icon Solutions, Ellicott City, MD) and applied the model to dose-exposure simulations. Pharmacodynamics endpoints were assessed at baseline and 3 hours after study drug administration, using postoperative hemodynamic monitoring lines. The analysis included 16 patients, 13 on ambrisentan (77 plasma samples); median age 36 months (range, 26-72 mo), weight 13.3 kg (11.1-17.6 kg), and nine males. There were no differences in baseline characteristics between ambrisentan and controls. A one-compartment model with first-order absorption and lag-time characterized the data well. Allometrically scaled weight was the only covariate retained in the final model. Typical values for clearance and volume of distribution were lower than previously reported in adults, 1 L/hr/70 kg and 13.7 L/70 kg, respectively. Simulated exposures with doses of 0.1-0.2 mg/kg approximated therapeutic exposures in adults with pulmonary arterial hypertension receiving 5 mg or 10 mg doses. Ambrisentan lowered plasma brain natriuretic peptide concentrations (452 ± 479 to 413 ± 462; p = 0.046), Fontan pressures (16.8 ± 2.9 to 15.6 ± 2.9; p = 0.01), and indexed pulmonary vascular resistance (2.3 ± 0.9 to 1.8 ± 0.6; p = 0.01) with no drug-related adverse events. CONCLUSIONS: Ambrisentan clearance is reduced following Fontan surgery, perhaps reflecting abnormal hepatic metabolism in this population. The observed safety profile appears favorable and hemodynamic effects of ambrisentan may be beneficial for Fontan patients.

Left-sided congenitally unguarded tricuspid valve with congenitally corrected transposition of the great arteries: A rare diagnosis confirmed by three-dimensional echocardiography.

Left-sided unguarded tricuspid valve disease with congenitally corrected transposition of the great arteries (ccTGA) is a rare cardiac malformation, only reported a few times in the literature. Two-dimensional echocardiography (2DE) uses standard views to diagnose tricuspid valve disease. Advanced imaging techniques, such as three-dimensional echocardiography, allow for simultaneous visualization of the tricuspid valve annulus and all leaflets. Three-dimensional echocardiography (3DE) may be useful in distinguishing unguarded tricuspid valve orifice from other forms of tricuspid valve disease.

Preprocedural three-dimensional planning aids in transcatheter ductal stent placement: A single-center experience.

OBJECTIVES: Describe the use of three-dimensional (3D) patent ductus arteriosus (PDA) modeling to better define ductal anatomy to improve preprocedural planning for ductal stent placement. BACKGROUND: Ductal stenting is an alternative to surgical shunting in patients with ductal dependent pulmonary blood flow. Ductal anatomy is often complex with extreme tortuosity and risk of pulmonary artery isolation, thus increasing procedural risks. METHODS: CT angiograms were segmented to produce 3D PDA models. Ductal morphology was characterized with attention to access approach, degree of pulmonary artery offset/risk of isolation and ductal tortuosity. 3D models were retrospectively compared with biplane angiography. RESULTS: 3D modeling was performed in 12 patients with adequate image quality for complete analysis in 11; median (interquartile range) age/weight 17 days (8-20 days) and 3.1 kg (2.4-3.9 kg). The PDA was reverse oriented in nine with average length of 17.2 ± 2.5 mm and high tortuosity (mean tortuosity index 52, range 3-108). From 3D modeling, two patients were excluded from ductal stenting-extreme ductal tortuosity and threatened pulmonary artery discontinuity, respectively. Ductal stenting was successful in the remaining nine with no major procedural complications. 3D modeling predicted a successful access approach based on the aortic orientation of the ductus in all patients (five carotid, two axillary, two femoral). When comparing 2D angiography with 3D models, angiography consistently underestimated ductal length (-3.2 mm ± 1.6 mm) and tortuosity (-14.8 ± 7.2). CONCLUSIONS: 3D modeling prior to ductal stent placement for ductal dependent pulmonary blood flow is useful in procedural planning, specifically for eligibility, access approach, and accurate ductal measurements. Further studies are needed to determine if 3D planning improves procedural outcomes.

Early cardiac dysfunction in children and young adults with perinatally acquired HIV.

OBJECTIVE: To define the prevalence of early cardiac dysfunction in children and young adults with perinatally acquired HIV and predictors of cardiac function. DESIGN: Cross-sectional design. METHODS: Early cardiac dysfunction was defined as left ventricular (LV) global longitudinal strain z-score less than -2 or myocardial performance index at least 0.5 with normal LV ejection fraction. Regression models were fitted to assess the relationship between measures of cardiac function and HIV RNA levels, clinical variables, and markers of inflammation. RESULTS: Six hundred and forty-three individuals (mean age 14.1 ±â€Š5.2 years) were enrolled. The average time on combination antiretroviral treatment was 6.8 ±â€Š3.6 years. Nearly 28% of individuals met criteria for early cardiac dysfunction. Individuals with early cardiac dysfunction were older (15.3 vs. 13.5 years, P < 0.001), had more frequently detectable HIV RNA (52.5 vs. 41.7%, P = 0.018), were more likely exposed to azidothymidine or zidovudine (ZDV) (55.6 vs. 41.2%, P = 0.002), and had higher median level of plasma IL-6 concentrations (1.00 vs. 0.88 pg/ml, P = 0.011). Multivariable models show LV ejection fraction negatively associated with HIV RNA levels [ß -0.18; 95% confidence interval (CI) -0.33, -0.03] and ZDV exposure (ß -1.75; 95% CI -2.62, -0.88) and positively associated with proportion of life on combination antiretroviral treatment (ß 2.65; 95% CI 0.90, 4.41). Higher myocardial performance index was positively associated with serum inflammation marker (IL-6 ß 0.01; 95% CI 0.0001, 0.001). Left ventricular global longitudinal strain was not significantly associated with clinical and laboratory variables of interest. CONCLUSION: Over one-quarter of children and young adults living with HIV demonstrated evidence of cardiac dysfunction, which may be associated with increasing levels of systemic inflammation.

Agreement of an echocardiogram-based diagnosis of pulmonary hypertension in infants at risk for bronchopulmonary dysplasia among masked reviewers.

OBJECTIVE: To evaluate the agreement of an echocardiogram-based pulmonary hypertension diagnosis in premature infants at risk for bronchopulmonary dysplasia (BPD). STUDY DESIGN: Echocardiograms from infants born ≤28 weeks post menstrual age were retrospectively reviewed with a standardized reading protocol by three pediatric cardiologists masked to patient's clinical history to determine the presence of pulmonary hypertension. RESULTS: A total of 483 echocardiograms from 49 unique patients were each reviewed by three pediatric cardiologists. Overall there was an 82.9% agreement on the presence of pulmonary hypertension among the three readers (95% CI: 78.4%, 85.4%) with a modified Fleiss' kappa of 0.759 (95% CI: 0.711, 0.801). Percent agreement between rereads was 92.4%, and modified Fleiss' kappa was 0.847 (95% CI: 0.750, 0.931). CONCLUSIONS: Using a standardized reading protocol and echocardiogram-based definition of pulmonary hypertension, there is high inter- and intra-rater agreement for the diagnosis of pulmonary hypertension in at-risk premature infants, suggesting echocardiography can be successfully used for clinical and research monitoring of pulmonary hypertension in infants.

Improving maternal-infant bonding after prenatal diagnosis of CHD.

BACKGROUND: Infants with prenatally diagnosed CHD are at high risk for adverse outcomes owing to multiple physiologic and psychosocial factors. Lack of immediate physical postnatal contact because of rapid initiation of medical therapy impairs maternal-infant bonding. On the basis of expected physiology, maternal-infant bonding may be safe for select cardiac diagnoses. METHODS: This is a single-centre study to assess safety of maternal-infant bonding in prenatal CHD. RESULTS: In total, 157 fetuses with prenatally diagnosed CHD were reviewed. On the basis of cardiac diagnosis, 91 fetuses (58%) were prenatally approved for bonding and successfully bonded, 38 fetuses (24%) were prenatally approved but deemed not suitable for bonding at delivery, and 28 (18%) were not prenatally approved to bond. There were no complications attributable to bonding. Those who successfully bonded were larger in weight (3.26 versus 2.6 kg, p<0.001) and at later gestation (39 versus 38 weeks, p<0.001). Those unsuccessful at bonding were more likely to have been delivered via Caesarean section (74 versus 49%, p=0.011) and have additional non-cardiac diagnoses (53 versus 29%, p=0.014). There was no significant difference regarding the need for cardiac intervention before hospital discharge. Infants who bonded had shorter hospital (7 versus 26 days, p=0.02) and ICU lengths of stay (5 versus 23 days, p=0.002) and higher survival (98 versus 76%, p<0.001). CONCLUSION: Fetal echocardiography combined with a structured bonding programme can permit mothers and infants with select types of CHD to successfully bond before ICU admission and intervention.

Evaluation of Right Ventricular Myocardial Mechanics Using Velocity Vector Imaging of Cardiac MRI Cine Images in Transposition of the Great Arteries Following Atrial and Arterial Switch Operations.

OBJECTIVE: The aim of the study was to determine right and left ventricle deformation parameters in patients with transposition of the great arteries who had undergone atrial or arterial switch procedures. SETTING: Patients with transposition are born with a systemic right ventricle. Historically, the atrial switch operation, in which the right ventricle remains the systemic ventricle, was performed. These patients have increased rates of morbidity and mortality. We used cardiac MRI with Velocity Vector Imaging analysis to characterize and compare ventricular myocardial deformation in patients who had an atrial switch or arterial switch operation. DESIGN: Patients with a history of these procedures, who had a clinically ordered cardiac MRI were included in the study. Consecutive 20 patients (75% male, 28.7 ± 1.8 years) who underwent atrial switch operation and 20 patients (60% male, 17.7 ± 1.9 years) who underwent arterial switch operation were included in the study. Four chamber and short-axis cine images were used to determine longitudinal and circumferential strain and strain rate using Vector Velocity Imaging software. RESULTS: Compared with the arterial switch group, the atrial switch group had decreased right ventricular ejection fraction and increased end-diastolic and end-systolic volumes, and no difference in left ventricular ejection fraction and volumes. The atrial switch group had decreased longitudinal and circumferential strain and strain rate. When compared with normal controls multiple strain parameters in the atrial switch group were reduced. CONCLUSIONS: Myocardial deformation analysis of transposition patients reveals a reduction of right ventricular function and decreased longitudinal and circumferential strain parameters in patients with an atrial switch operation compared with those with arterial switch operation. A better understanding of the mechanisms of right ventricle failure in transposition of great arteries may lead to improved therapies and adaptation.