Mark K. Friedberg

Pediatric Pulmonary Hypertension Guidelines From the American Heart Association and American Thoracic Society

Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension.

Comparison between Different Speckle Tracking and Color Tissue Doppler Techniques to Measure Global and Regional Myocardial Deformation in Children

BACKGROUND Myocardial deformation parameters obtained by speckle-tracking echocardiography (STE) and color Doppler tissue imaging (CDTI) using two different ultrasound systems and three different software packages were compared. METHODS Apical four-chamber, short-axis grayscale, and color Doppler tissue images were prospectively acquired using Vivid 7 and iE33 ultrasound systems in 34 children and then analyzed using EchoPAC and QLAB (STE) and SPEQLE (CDTI). RESULTS Measurement of myocardial deformation was feasible for all three modalities. Longitudinal strain (epsilon) measurements showed the lowest intraobserver and interobserver variability (intraobserver and interobserver coefficients of variation, 9% and 8% for EchoPAC, 5% and 6% for QLAB, and 14% and 16% for SPEQLE). In addition, longitudinal epsilon had a small bias and narrow limits of agreement when comparing different techniques. The coefficients of variation of circumferential epsilon by EchoPAC and QLAB were 12% and 11% (intraobserver) and 9% and 13% (interobserver), respectively. Circumferential epsilon by STE had a small systematic bias but relatively narrow limits of agreement. The reproducibility of radial epsilon measurements using STE was low, while CDTI epsilon provided better performance (intraobserver and interobserver coefficients of variation for radial posterior epsilon, 12% and 24% for EchoPAC, 39% and 56% for QLAB, and 12% and 14% for SPEQLE). Radial epsilon was on average 50% lower using QLAB compared with EchoPAC and SPEQLE. Systolic strain rate values obtained by STE were lower compared with CDTI-derived values. The limits of agreement for strain rate values among the three modalities were wide, and intraobserver and interobserver variability was poor for all three modalities. CONCLUSIONS Some deformation measurements (e.g., longitudinal and circumferential epsilon) are comparable among different ultrasound machines and software packages, whereas others are significantly different (e.g., radial epsilon and strain rate). This study stresses the need for an industry standard for these techniques.

Right Versus Left Ventricular Failure Differences, Similarities, and Interactions

Ventricular failure manifests in many forms, its underlying physiology ranging from overt left ventricular (LV) systolic dysfunction to isolated right ventricular (RV) diastolic dysfunction, and the wide portfolio of resulting symptoms vary from chronic fluid retention to acute multiorgan dysfunction and death. In this review, we discuss the morphological, functional, and molecular similarities and differences in RV and LV responses to adverse loading and failure. We further discuss whether LV and RV function and failure can truly be discussed as separate entities and thereby examine interactions between the ventricles that on one hand contribute to ventricular dysfunction but on the other may be harnessed for therapeutic benefit. The RV and LV have different embryological origins.1 The LV originates from the primary heart field; the RV, from the secondary heart field. Consequently, several genes specifically control RV formation, including, among others, Hand2 and Tbx20 .2 During gestation, the RV functions as the systemic ventricle (Figure 1A). During fetal life, in addition to supplying the modest amount of pulmonary blood flow, the RV pumps blood to the lower body and placenta and contributes more than half of the combined cardiac output.3 With the transition from fetal to postnatal physiology and with the reduction in pulmonary vascular resistance, the subpulmonary RV transforms its morphology and geometry, becoming a thin-walled chamber to adopt its postnatal physiological characteristics.4 Because it faces a low impedance pulmonary circulation, the normal postnatal RV maintains a cardiac output equal to that of the LV at approximately a fifth of the energy cost. The trapezoidal RV pressure-volume loop reflects this difference, with few if any isovolumic periods. Consequently, RV output starts early during pressure generation and is later maintained by a “hangout period” when antegrade flow continues into the pulmonary artery despite the onset of RV …

Complete heart block associated with device closure of perimembranous ventricular septal defects

OBJECTIVE The development of the Amplatzer Membranous VSD Occluder (AGA Medical Corp, Plymouth, Minn) for closure of the perimembranous ventricular septal defect has ameliorated many of the technical difficulties of previous devices. Application of this new technology requires comparative evaluation with the current standard of surgical repair. We report our experience of complete heart block associated with device closure of a large perimembranous ventricular septal defect with unequivocal indications for intervention. METHODS We performed a retrospective review of 20 patients between January 2003 and August 2005 who underwent perimembranous ventricular septal defect device closure, 18 with hemodynamically large shunts meeting the surgical criteria for intervention. The median age was 1.6 years (range, 0.5-16.2 years), and the median weight was 9.7 kg (range, 6.2-43 kg). RESULTS Acute complete shunt occlusion was achieved in all patients. There were no acute procedural complications. The median follow-up time was 23.1 months (range, 1-37.8 months). Four (22%) had complete heart block at 17 days, 4.2 months, 8.8 months, and 37.5 months after implantation, respectively. No risk factors were identified for development of complete heart block, including age, weight, trisomy 21, preceding conduction abnormalities, perimembranous ventricular septal defect size related to body surface area or device size, and progressive device flattening. CONCLUSIONS Device closure of large perimembranous ventricular septal defects in infants and children with the Amplatzer Membranous VSD Occluder resulted in excellent closure rates but an unacceptably high rate of complete heart block.

Usefulness of the right ventricular systolic to diastolic duration ratio to predict functional capacity and survival in children with pulmonary arterial hypertension.

The objective of this study was to investigate the systolic to diastolic duration ratio (S:D ratio) in children with pulmonary arterial hypertension (PAH) and its association with right ventricular (RV) performance, hemodynamics, 6-minute walk test, clinical outcomes, and survival. We reviewed 503 serial echocardiograms in 47 children with PAH (mean pulmonary artery pressure >or=25 mm Hg) and compared the S:D ratio, assessed from Doppler flow of tricuspid valve regurgitation, to that in 47 age-matched controls. We reviewed echocardiograms, catheterization data, 6-minute walk tests, clinical data, lung transplantation, and death and used univariate linear regression models with a maximum likelihood algorithm for parameter estimation to investigate associations between S:D ratio and RV function, hemodynamics, functional capacity, and clinical outcomes. The S:D ratio was significantly higher in patients than in controls (1.38 +/- 0.61 vs 0.72 +/- 0.16, p <0.001). A higher S:D ratio was associated with worse echocardiographic RV fractional area of change, worse catheterization hemodynamics, shorter 6-minute walk distance, and worse clinical outcomes independent of pulmonary resistance or pressures. An increase of 0.1 in the S:D ratio was associated with a 13% increase in yearly risk for lung transplantation or death (hazard ratio 1.13, p <0.001). An S:D ratio 1.00 to 1.40 was associated with a moderate risk and an S:D ratio >1.40 was associated with a high risk of a negative outcome. In conclusion, in children with PAH, an increased S:D ratio is temporally associated with worse RV function, hemodynamics, exercise capability, clinical status, and survival.

Tissue velocities, strain, and strain rate for echocardiographic assessment of ventricular function in congenital heart disease

During the last decade tissue Doppler and myocardial deformation imaging has been introduced to quantify myocardial function in patients with congenital heart disease. These methods could have potential benefits for patients where the anatomy makes it difficult to quantify ventricular function using M-mode or two-dimensional volumetric techniques. In this overview, the potential benefits as well as limitations of the techniques are discussed. Looking directly into the myocardium renders the techniques geometry-independent, allowing the quantification of right ventricular as well as univentricular systolic function. The limitations include the influence of variable loading conditions as well as different methodological problems.

Validation of 3D echocardiographic assessment of left ventricular volumes, mass, and ejection fraction in neonates and infants with congenital heart disease: a comparison study with cardiac MRI.

Background—Quantitative assessment and validation of left ventricular (LV) volumes and mass in neonates and infants with complex congenital heart disease (CHD) is important for clinical management but has not been undertaken. We compared matrix-array 3D echocardiography (3D echo) measurements of volumes, mass, and ejection fraction (EF) with those measured by cardiac MRI in young patients with CHD and small LVs because of either young age or LV hypoplasia. Methods and Results—Thirty-five patients aged <4 years (median, 0.8 years) undergoing MRI were prospectively enrolled. Three-dimensional echo was acquired immediately after MRI, and volume, mass, and EF measurements, using summation of discs methodology, were compared with MRI. Three-dimensional echo end-diastolic volume (24.4±15.7 versus 24.8±46.4 mL; P=0.01; intraclass correlation coefficient [ICC], 0.96) and end-systolic volume (12.3±8.6 versus 9.6±6.8 mL; P<0.001; ICC, 0.90) correlated with MRI with small mean differences (−0.49 mL [P=0.6] and 2.7 mL [P=0.001], respectively). Three-dimensional echo EF was smaller than MRI by 9.3% (P<0.001), and 3D echo LV mass measurements were comparable to MRI (17.3±10.3 versus 17.6±12 g; P<0.77; ICC, 0.93), with a small mean difference (1.1 g; P=0.28). There was good intra- and interobserver reliability for all measurements. Conclusions—In neonates and infants with CHD and small LVs (age appropriate or hypoplastic), matrix-array 3D echo measurements of mass and volumes compare well with MRI, providing an important modality for ventricular size and performance analysis in these patients, particularly in those with left-side heart obstructive lesions.

Permanent Cardiac Pacing in Children: Choosing the Optimal Pacing Site A Multicenter Study

Background— We evaluated the effects of the site of ventricular pacing on left ventricular (LV) synchrony and function in children requiring permanent pacing. Methods and Results— One hundred seventy-eight children (aged <18 years) from 21 centers with atrioventricular block and a structurally normal heart undergoing permanent pacing were studied cross-sectionally. Median age at evaluation was 11.2 (interquartile range, 6.3–15.0) years. Median pacing duration was 5.4 (interquartile range, 3.1–8.8) years. Pacing sites were the free wall of the right ventricular (RV) outflow tract (n=8), lateral RV (n=44), RV apex (n=61), RV septum (n=29), LV apex (n=12), LV midlateral wall (n=17), and LV base (n=7). LV synchrony, pump function, and contraction efficiency were significantly affected by pacing site and were superior in children paced at the LV apex/LV midlateral wall. LV dyssynchrony correlated inversely with LV ejection fraction (R=0.80, P=0.031). Pacing from the RV outflow tract/lateral RV predicted significantly decreased LV function (LV ejection fraction <45%; odds ratio, 10.72; confidence interval, 2.07–55.60; P=0.005), whereas LV apex/LV midlateral wall pacing was associated with preserved LV function (LV ejection fraction ≥55%; odds ratio, 8.26; confidence interval, 1.46–47.62; P=0.018). Presence of maternal autoantibodies, gender, age at implantation, duration of pacing, DDD mode, and QRS duration had no significant impact on LV ejection fraction. Conclusions— The site of ventricular pacing has a major impact on LV mechanical synchrony, efficiency, and pump function in children who require lifelong pacing. Of the sites studied, LV apex/LV midlateral wall pacing has the greatest potential to prevent pacing-induced reduction of cardiac pump function.

Prognostic significance of 2-dimensional, M-mode, and Doppler echo indices of right ventricular function in children with pulmonary arterial hypertension

BACKGROUND Echocardiographic measures of right ventricular (RV) function are associated with adverse outcomes in adults with idiopathic pulmonary arterial hypertension (iPAH) but have not been adequately studied in children. We investigated the prognostic value of 2D, M-mode and Doppler indices of RV function in relation to death or lung transplant in children with iPAH and PAH associated with congenital heart diseases (cPAH). METHODS Children with iPAH and cPAH were studied. Two echocardiograms were analyzed for each patient: at diagnosis and at last follow-up. Clinical data, catheter hemodynamics and 6-minute walk distance were recorded. Echo indices of RV function were compared between the first and follow-up echo, between iPAH and cPAH patients, and between iPAH patients alive at follow-up versus those who had died or had undergone lung transplant. Survival probability stratified by RV function was analyzed. RESULTS Fifty-four children were studied: 36 cPAH patients (7.5 ± 5.9 years) and 18 iPAH patients (8.9 ± 5.7 years) of whom 12 were alive and 6 had died or were transplanted. Despite similar pulmonary hemodynamics, RV function, including right atrial volume, tricuspid annular planar excursion, fractional area of change, and left ventricular eccentricity index were worse in iPAH at presentation and at follow-up. At last echo there was further worsening of RV function in iPAH patients, particularly in those who had died or were transplanted, compared with improved or unchanged indices in cPAH patients or iPAH survivors. CONCLUSION Conventional echo RV functional parameters are valuable to identify risk for transplant or death in children with PAH.

Echocardiographic Assessment of Right Ventricular Volumes after Surgical Repair of Tetralogy of Fallot: Clinical Validation of a New Echocardiographic Method

BACKGROUND Assessment of right ventricular (RV) volumes and function is important in patients after tetralogy of Fallot (TOF) repair. Currently, cardiac magnetic resonance imaging (MRI) is considered the clinical reference method for RV volume and function measurements. Three-dimensional (3D) knowledge-based reconstruction derived from two-dimensional echocardiographic imaging with magnetic tracking is a novel approach to RV volumetrics. The aim of this study was to assess the feasibility and reliability of this novel echocardiographic technique in patients after TOF repair. The accuracy of the method was assessed by comparison with measurements obtained by cardiac MRI. METHODS Thirty patients (mean age, 13.7 ± 2.8 years) after TOF repair, referred for cardiac MRI, were included. Immediately after MRI, echocardiographic image acquisition was performed using a standard ultrasound scanner linked to a Ventripoint Medical Systems unit. Echocardiographic and MRI measurements were performed offline. Parameters analyzed were end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction. Intraobserver, interobserver, and intertechnique variability was assessed using Pearsons correlation analysis, coefficients of variation, and Bland-Altman analysis. RESULTS Echocardiographic two-dimensionally based 3D reconstruction was highly feasible, with low intraobserver and interobserver variability for EDV and slightly higher variability for ESV and ejection fraction. The 3D reconstruction values for EDV, ESV, and ejection fraction were correlated highly with MRI values, with low coefficients of variation. The agreement between both methods was high. Three-dimensional reconstruction slightly underestimated RV volumes, by 2.5% for EDV and 4.6% for ESV compared with MRI volumes. CONCLUSIONS In patients after TOF repair, echocardiographic 3D reconstruction is highly feasible, with good reproducibility for measurements of RV EDV. There is good agreement with MRI measurements, with a small underestimation of RV volumes. The use of this method in clinical practice warrants further investigation.