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Graphical abstract, Highlights • Cardiac interdependence in conjoined twins is a rare phenomenon. • Presence of congenital heart disease may be an important prognostic factor. • There is high risk of high-output heart failure and pulmonary hypertension in the donor twin. • If reconstruction is feasible, early separation may improve the chance of survival.

BACKGROUND: Retrospective multicenter research using echocardiograms obtained for routine clinical care can be hampered by issues of individual center quality, thus limiting the application of post-hoc research analytics. We sought to evaluate imaging and patient characteristics associated with poorer quality of archived echocardiograms from a cohort of childhood cancer survivors. METHODS: A single blinded reviewer at a central core lab graded quality of clinical echocardiograms from 5 contributing centers focusing on images to derive 2D and M-mode fractional shortening (FS), biplane Simpson ejection fraction (EF), myocardial performance index (MPI), tissue Doppler imaging (TDI) derived velocities and global longitudinal strain (GLS). RESULTS: Of 535 studies analyzed in 102 subjects from 2004 to 2017, all measures of cardiac function could be assessed in only 7%. While FS by 2D or M-mode, MPI and septal E/E’ could be measured in >80% studies, mitral E/E’ was less consistent (69%), but better than EF (52%) and GLS (10%). At least one quality issue was identified in 66% studies, with technical issues (ex. lung artifact, poor endocardial definition) being the most common (33%). Lack of 2- and 3-chamber views was associated with the performing center. Patients < 5 years had a higher chance of apex cut-off in 4-chamber views compared to 16–35 year old (RR 1.99 (1.07–3.72), p = 0.03). Overall, for any quality issue, earlier era of echo and center were the only significant risk factors. CONCLUSION: Assessment of cardiac function using pooled multicenter archived echocardiograms was significantly limited. Efforts to standardize clinical echocardiographic protocols to include apical 2- and 3-chamber views and TDI will improve the ability to quantitate LV function.

Objectives: The purpose of this study was to assess the timing of changes in serial echocardiographic parameters in pediatric cancer survivors and to evaluate their associations with cardiomyopathy development. Background: Pediatric cancer survivors undergo serial echocardiograms to screen for cardiotoxicity. It is not clear whether small longitudinal changes in functional or structural parameters over time have clinical significance. Methods: This is a multicenter, retrospective, case-control study of ≥1-year survivors following the end of cancer therapy. Cardiomyopathy cases (fractional shortening [FS] ≤28% or ejection fraction [EF] ≤50% on ≥2 occasions) were matched to control subjects (FS ≥30%, EF ≥55%, not on cardiac medications) by cumulative anthracycline and chest radiation dose, follow-up duration, and age at diagnosis. Digitally archived clinical surveillance echocardiograms were quantified in a central core laboratory, blinded to patient characteristics. Using mixed models with interaction terms between time and case status, we estimated the least square mean differences of 2-dimensional, M-mode, pulsed wave Doppler, and tissue Doppler imaging–derived parameters over time between cases and control subjects. Results: We identified 50 matched case-control pairs from 5 centers. Analysis of 412 echocardiograms (cases, n = 181; control subjects, n = 231) determined that indices of left ventricular systolic function (FS, biplane EF), diastolic function (mitral E/A ratio), and left ventricular size (end-diastolic dimension z-scores) were significantly different between cases and control subjects, even 4 years prior to the development of cardiomyopathy. Conclusions: Longitudinal changes in cardiac functional parameters can occur relatively early in pediatric cancer survivors and are associated with the development of cardiomyopathy.

Introduction Right ventricular pacing is associated with pacemaker induced cardiomyopathy and lesser degrees of pacing-induced LV dysfunction (PIVD) manifested by a reduction in left ventricular ejection fraction (LVEF). Our objective was to determine whether apical 4 chamber strain (A4C) by echocardiography can identify patients at risk of PIVD before LVEF declines. Methods and results A retrospective chart review of patients (0-21 years) who had a pacemaker with a ventricular lead placed between 2011 and 2017 was performed. Patients were divided into group A (LVEF 10% decline in LVEF within 12 months of pacemaker placement) and group B. Data have collected before and 1 and 12 months postpacemaker implantation. There were 30 patients in the group A and 60 in group B. At 1 and 12 months postpacemaker implantation, the LVEF was significantly lower while the A4C and QRS duration on electrocardiogram were significantly higher in the group A. While the LVEF and A4C became markedly abnormal in group A as early as 1 month, the A4C did not seem to demonstrate such marked abnormalities in group B. However, a sub-analysis of patients in the group A with preserved LVEF at 1 month demonstrated significant worsening in their A4C at that time. Conclusion Myocardial deformation imaging may be a clinically useful tool for the prediction of a decline in LV systolic function following pacemaker implantation. Abnormalities in A4C seem to appear before LVEF decline and as soon as 1-month postpacemaker implantation.

Background: Published palliation outcomes of infants with functional single ventricle (SV) and common atrioventricular septal defect (AVSD) are poor due to associated cardiac and extracardiac anomalies and development of atrioventricular valve (AVV) regurgitation. We report current palliation results. Methods: From 2002 to 2012, 80 infants with functional SV with AVSD underwent multistage palliation. Competing-risks analyses modeled events after first-stage surgery and Glenn (death/transplantation vs next palliation surgery) and examined factors associated with survival and AVV intervention. Results: Sixty-eight (80%) patients received neonatal palliation: modified Blalock-Taussig shunt (n = 33, 41%), Norwood (n = 20, 25%), and pulmonary artery band (n = 15, 19%), whereas 12 (15%) received primary Glenn. On competing-risks analysis, one-year following first-stage surgery, 29% of patients had died or received transplantation and 62% had undergone Glenn. Five years following Glenn, 9% of patients had died or received transplantation and 68% had undergone Fontan. Overall eight-year survival was 64% and was lower in patients with genetic syndromes (53% vs 82%), patients requiring concomitant total anomalous pulmonary venous connection repair (53% vs 69%), and those requiring neonatal palliation (48% vs 100%). Factors associated with mortality were unplanned reoperation (hazard ratio [HR]: 3.7 [1.7-8.0], P = .001) and extracorporeal membrane oxygenation use (HR: 7.1 [3.0-16.6], P < .001). Initial AVV regurgitation ≥ moderate was associated with AVV intervention (HR: 6.2 [2.4-16.1], P = .002) with eight-year freedom from death or AVV intervention of 25% in those patients. Conclusions: Patients with SV with AVSD are a distinct group and commonly have associated cardiac and extracardiac malformations that complicate care and affect survival. The development of AVV regurgitation requiring intervention is common but does not affect survival.

Introduction: Adverse outcomes in hypertrophic cardiomyopathy (HCM) includes arrhythmias, myocardial fibrosis, heart failure, and sudden cardiac arrest (SCA). These are well documented in children. Exercise stress echocardiography (ESE) can identify the severity and mechanism of left ventricular outflow tract (LVOT) obstruction that may not be present at rest. Our aim was to compare clinical outcomes in pediatric patients with varying severity of LVOT obstruction. Methods: We reviewed records of patients < 22 years with HCM who underwent staged ESE Jan 2009 - Dec 2019 at our center. Patients were divided into 3 groups: no resting or exercise LVOT gradient (Group 1), no resting gradient with LVOT gradient > 30 mmHg at peak exercise (Group 2), and resting LVOT gradient > 30 mmHg (Group 3). We assessed echocardiographic indices, advanced imaging, and clinical data. Statistical analysis performed with p-value Results: 93 patients met inclusion criteria. 6 SCA events occurred, though not during ESE.. Patients in Group 3 were classified less often as NYHA Class 1 compared to Group 1 or Group 2, (p < 0.01). Group 3 had the highest rate of myectomy (p=0.005) and ICD placement (p=0.003). There was no significant difference in exercise symptoms, peak oxygen consumption, or ischemic changes during ESE between the groups. Peak heart rate was also higher in Group 2 with no difference in blood pressure response. Groups were not associated with family history of disease, positive gene status, SCA, or the presence of fibrosis (Table). LVOT gradients differed as early as Stage 1 in Groups 1 & 2. Inducible LVOT obstruction was most commonly midcavitary in Group 2. Conclusion: The presence of resting versus inducible LVOT obstruction in pediatric HCM does not appear associated with adverse outcomes. This may be hampered by the rarity of events in pediatrics. The predominant mechanism of inducible LVOT obstruction was midcavitary, which has a link to adverse long-term outcomes in adult HCM.

Background: Elevated left ventricular outflow tract (LVOT) gradients during exercise can occur in patients with hypertrophic cardiomyopathy (HCM) as well as in athletes and normal controls. The authors’ staged exercise protocol calls for imaging at rest and during each stage of exercise to evaluate the mechanism of LVOT obstruction at each stage. They investigated whether this staged approach helps differentiate HCM from athletes and normal controls. Methods: They reviewed pediatric exercise stress echocardiograms completed between January 2009 and October 2017 at their center and identified those with gene-positive HCM, athlete’s heart, and normal controls. Children with inducible obstruction (those with no LVOT gradient at rest who developed a LVOT peak gradient > 25 mm Hg during exercise) were included. LVOT peak gradient, velocity time integral, acceleration time, and deceleration time were measured at rest, submaximal stages, and peak exercise. Results: Compared with athletes, HCM patients had significantly higher LVOT peak gradients at rest (P = .019), stage 1 of exercise (P = .002), and peak exercise (P = .051), as well as a significantly higher change in LVOT peak gradient from rest to stage 1 (P = .016) and from rest to peak (P = .038). The acceleration time/deceleration time ratio of the LVOT Doppler was significantly lower in HCM patients compared with normal controls at peak exercise. Conclusions: The HCM patients who develop elevated LVOT gradients at peak exercise typically manifest early obstruction in the submaximal stages of exercise, which helps to differentiate them from athletes and normal controls.

TDI-MPI has been shown to predict cardiovascular mortality in adults; there are a paucity of data on its use in children. We sought to determine the prognostic significance of TDI-MPI at time of DCM diagnosis in children. Patients aged ≤18 years diagnosed with DCM were included along with age- and sex-matched controls. Echo at diagnosis was analyzed to obtain standard measures of LV function, PW-MPI, and septal and LV free wall TDI-MPI. Survival analysis was used to assess the time to composite outcome of death, VAD, or transplant, stratified by TDI-MPI z-score. The study included 79 patients with DCM and 79 controls. During a median follow-up of 182 days (IQR 41–815 days), 16 underwent VAD placement, 21 underwent cardiac transplant, 6 died, and 36 had event-free survival. The median septal TDI-MPI for cases was 0.70 for patients with DCM vs 0.45 for controls (P < .001). Those with septal TDI-MPI z-scores ≥2 develop events significantly earlier than those with z-score

ObjectiveTo enhance the understanding of cardiovascular care delivery in childhood cancer patients and survivors.Study designA 20-question survey was created by the Pediatric Cardio-oncology Work Group of the American College of Cardiology (ACC) Cardio-oncology Section to assess the care, management, and surveillance tools utilized to manage pediatric/young adult cardio-oncology patients. The survey distribution was a collaborative effort between Cardio-oncology Section and membership of the Adult Congenital and Pediatric Cardiology Section (ACPC) of the ACC.ResultsSixty-five individuals, all self-identified as physicians, responded to the survey. Most respondents (n = 58,89%) indicated childhood cancer patients are regularly screened prior to and during cancer therapy at their centers, predominantly by electrocardiogram (75%), standard echocardiogram (58%) and advanced echocardiogram (50%) (i.e. strain, stress echo). Evaluation by a cardiologist prior to/during therapy was reported by only 8(12%) respondents, as compared to post-therapy which was reported by 28 (43%,p n = 31,48%) and history of chemotherapy exposure (n = 27,42%). Of note, during post-treatment counseling, common cardiovascular risk-factors like blood pressure (31,48%), lipid control (22,34%), obesity & smoking (30,46%) and diet/exercise/weight loss (30,46%) were addressed by fewer respondents than was LV function (72%).ConclusionsThe survey data demonstrates that pediatric cancer patients are being screened by EKG and/or imaging prior to/during therapy at most centers. Our data, however, highlight the potential for greater involvement of a cardiovascular specialist for pre-treatment evaluation process, and for more systematic cardiac risk factor counseling in posttreatment cancer survivors.

To describe the role of big data in cardio-oncology. There is a trend towards developing cloud-based, integrated registries to improve data collection, access, and analysis. Using a template from pediatric oncology, a cardio-oncology data commons is a novel opportunity to integrate data elements into a cloud-based platform. A cloud-based registry provides advantages of multi-institutional collaboration, rapid data access, a virtual visualization, and analytic tools to reduce infrastructure redundancy. The data commons would include integrated clinical data, blood samples, and genomic data to streamline discovery and analysis for researchers. A cardio-oncology data commons would be a large step forward in bringing cardio-oncology to the forefront of big data.

BACKGROUND Left ventricular outflow tract obstruction (LVOTO) is a common complication following surgical repair of atrioventricular septal defect (AVSD). OBJECTIVE We sought to determine predictors of LVOTO based on echocardiograms performed prior to initial repair of AVSD. METHODS Of the 415 children that had repair of AVSD from 2003 to 2012, 17 children were identified with LVOTO that required surgical intervention. Thirty-four patients with repaired AVSD and no LVOTO served as controls. Patient demographics, cardiac surgery type, and echocardiogram results at last follow-up were collected. Off-line analysis of the echocardiogram prior to AVSD repair was done to obtain: left ventricular outflow tract (LVOT) and interventricular septal diameter, chordae across LVOT, aortoseptal angle, left ventricular (LV) inflow/outflow length ratio, inferior displacement of the atrioventricular (AV) valve, atrioventricular valve index (AVVI) and presence of coarctation of the aorta. RESULTS The LVOTO group had significantly smaller indexed LVOT diameters (P

Background Qualitative assessment of ventricular septal flattening is commonly used in pediatric patients with pulmonary hypertension (PH) who lack adequate tricuspid regurgitation (TR) Doppler signal. We sought to determine the relation between quantitative measures of septal flattening including the eccentricity index (EIs) and a novel marker, the septal flattening angle (SFA) with right ventricular systolic pressure (RVSP). Methods Subjects (≤18 years) with an anatomically normal heart, an adequate TR signal to obtain a peak velocity, and a simultaneous systemic systolic blood pressure (SBP) was included. RVSP was derived using TR gradient. Eccentricity index (EIs) and the SFA in systole were measured offline and correlated with RVSP/SBP. Results Of the 108 subjects, RVSP/SBP was < 50% in 77 and ≥ 50% in 31. In those with RVSP/SBP ≥50%, the median SFA was significantly lower (7.4° vs. 22°, p < 0.0001), and the median EIs was higher (1.61 vs. 1.07, p < 0.0001). SFA and EIs had a significant correlation with RVSP/SBP (rs = −0.70 and 0.61, respectively). Area under the curve was higher for SFA compared to EIs (0.92 and 0.85, respectively). The sensitivity and specificity of SFA for predicting an RVSP/SBP ≥ 50% using a cut point of 16° was 84% and 95% and for an EIs cut point of 1.35 was 74.2% and 96.1%, respectively. Conclusion Septal flattening angle and EIs are quantitative measures of ventricular septal flattening that correlate well with RVSP/SBP and should be considered more routinely in clinical practice, especially in patients with inadequate TR Doppler signal.

Patients with a Fontan circulation have impaired exercise capacity. Cardiac rehabilitation (CR) has shown promise in enhancing peak exercise parameters in this population, but an improvement in submaximal exercise has not been consistently demonstrated. We assessed the hypothesis that participation in CR will be associated with more efficient oxygen extraction and ventilation during submaximal exercise. In this prospective study, pediatric Fontans completed two 60 min CR sessions per week for 12 weeks. Cardiopulmonary exercise testing and stress echocardiography were performed at baseline and last CR session, and then compared with a paired sample t test. Ten pediatric Fontans completed the study. Five had tricuspid atresia and five had hypoplastic left heart syndrome. No serious adverse events occurred during CR sessions. Peak indexed oxygen consumption increased by a mean of 3.7 mL/kg/min (95% CI 1.5–5.9; p = 0.004), and peak oxygen pulse increased by a mean of 0.9 mL/beat (95% CI 0.4–1.4; p = 0.004). The peak respiratory exchange ratio did not change significantly. The significant difference in oxygen pulse became evident during submaximal exercise without a corresponding difference in echocardiographic stroke volume. Indexed oxygen consumption at ventilatory anaerobic threshold increased by a mean of 3.0 mL/kg/min (95% CI − 0.07 to 6.0; p = 0.055). The slope for the volume of expired ventilation to volume of carbon dioxide production improved by a mean of 4.5 (95% CI − 8.4 to − 0.6; p = 0.03). We observed significant improvements in both submaximal and peak exercise performance in pediatric Fontans undergoing CR with no serious adverse events. These changes appeared to be mediated, at least in part, by more efficient oxygen extraction and ventilation.

Background Surveillance for anthracycline cardiotoxicity in cancer survivors typically utilizes resting M-mode and two-dimensional echocardiography, which are insensitive to detection of subtle myocardial changes. We examined childhood cancer survivors treated with anthracyclines during exercise using various echocardiography techniques to investigate if these tools can better detect subclinical cardiac dysfunction. Procedure We recruited asymptomatic survivors at least five years post treatment. Echocardiography was performed at rest and at termination of exercise utilizing tissue Doppler techniques and strain rate imaging. Results Eighty participants were characterized by cardiotoxicity risk status (high [12], moderate [23], low [24], no risk [21]) as defined by the Children's Oncology Group Long Term Follow-Up Guidelines v3.0. The high-risk group had a higher resting heart rate than controls (100 vs. 88 bpm [P for trend = 0.049]). Peak aerobic capacity in all groups was similar. Compared to controls at rest, the high-risk group had evidence of diastolic dysfunction with lower E/A ratios (1.4 vs. 2.0, P = 0.008) and higher septal early diastolic velocities (E/E') of 11.7 versus 9.9 (P = 0.165). With exercise, this difference resolved and myocardial contractile reserve was preserved. Conclusions Asymptomatic, pediatric cancer survivors at high-risk for anthracycline cardiotoxicity have some evidence of diastolic filling abnormalities at rest. With exercise, they augment their systolic and diastolic function to achieve normal maximal aerobic capacity suggesting they are able to compensate for mild cardiac dysfunction in the early years after exposure. Additionally, findings suggest that routine exercise echocardiography may not be a useful surveillance tool to assess anthracycline cardiotoxicity. Pediatr Blood Cancer 2015;62:502–508. © 2014 Wiley Periodicals, Inc.

Background— The Pediatric Heart Network’s Single Ventricle Reconstruction (SVR) trial randomized infants with single right ventricles (RVs) undergoing a Norwood procedure to a modified Blalock-Taussig or RV-to-pulmonary artery shunt. This report compares RV parameters in the 2 groups using 3-dimensional echocardiography. Methods and Results— Three-dimensional echocardiography studies were obtained at 10 of 15 SVR centers. Of the 549 subjects, 314 underwent 3-dimensional echocardiography studies at 1 to 4 time points (pre-Norwood, post-Norwood, pre–stage II, and 14 months) for a total of 757 3-dimensional echocardiography studies. Of these, 565 (75%) were acceptable for analysis. RV volume, mass, mass:volume ratio, ejection fraction, and severity of tricuspid regurgitation did not differ by shunt type. RV volumes and mass did not change after the Norwood, but increased from pre-Norwood to pre–stage II (end-diastolic volume [milliliters]/body surface area [BSA] 1.3 , end-systolic volume [milliliters]/BSA 1.3 , and mass [grams]/BSA 1.3 mean difference [95% confidence interval]=25.0 [8.7–41.3], 19.3 [8.3–30.4], and 17.9 [7.3–28.5], then decreased by 14 months (end-diastolic volume/BSA 1.3 , end-systolic volume/BSA 1.3 , and mass/BSA 1.3 mean difference [95% confidence interval]=−24.4 [−35.0 to −13.7], −9.8 [−17.9 to −1.7], and −15.3 [−22.0 to −8.6]. Ejection fraction decreased from pre-Norwood to pre–stage II (mean difference [95% confidence interval]=−3.7 [−6.9 to −0.5]), but did not decrease further by 14 months. Conclusions— We found no statistically significant differences between study groups in 3-dimensional echocardiography measures of RV size and function, or magnitude of tricuspid regurgitation. Volume unloading was seen after stage II, as expected, but ejection fraction did not improve. This study provides insights into the remodeling of the operated univentricular RV in infancy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00115934.

Background Right ventricular systolic dysfunction (RVSD) is a predictor of outcomes in dilated cardiomyopathy (DCM) in adults, but little is known in children. Tricuspid annular plane systolic excursion (TAPSE) has emerged as a reliable tool to assess RVSD. We sought to determine the prevalence and prognostic significance of RVSD using TAPSE in children with DCM. Methods The first echocardiogram at the time of diagnosis with DCM was analyzed to obtain left ventricular ejection fraction (LVEF) and 2D TAPSE. RVSD was defined as TAPSE age-based z-score ≤−2. The association of a composite primary endpoint including death, mechanical support, or transplantation with RVSD was analyzed using LVEF and TAPSE. Results Of the 96 patients, RVSD was noted in 84 (88%). During a median follow-up of 17.5 months (IQR 1.4, 76.2), the primary endpoints were reached in 59%. There was a lower LVEF in patients with RVSD (P=.016). Moderate or severe RVSD showed a significant association with the composite primary endpoint (unadjusted OR 2.7 [95% CI: 1.15–6.33], P=.023). Kaplan-Meier analysis showed that the event-free survival was significantly lower in patients with LVEF ≤30% and TAPSE z-score ≤−4. Conclusion Children with DCM have a high prevalence of RVSD based on reduced TAPSE, and those with moderate or severe RVSD have worse clinical outcomes.

Background Hypertrophic cardiomyopathy (HCM) is associated with decreased exercise tolerance in children, presumably due to diastolic dysfunction. Modern imaging techniques to assess myocardial function during active exercise have not been applied to this population. We hypothesized that impaired contractile reserve, as assessed by tissue Doppler imaging (TDI) and strain, contributes to reduced exercise capacity in affected individuals. Methods Children (

This case study describes a newborn male infant with cat eye syndrome, found to have a rare constellation of congenital defects, which included an interrupted aortic arch, type B2 (with aberrant right subclavian artery), aortic valve atresia, aorto-pulmonary window, left coronary artery to pulmonary artery fistula, ventricular septal defect, atrial septal defect, and a restrictive patent ductus arteriosus.

Background The prognostic value of deformation parameters of the systemic right ventricle in adults with D-transposition of the great arteries and prior atrial switch has not been reported. Methods Sixty-four adults with D-transposition of the great arteries and prior atrial switch (mean age, 29 ± 6 years; 22 women; mean right ventricular [RV] fractional area change, 22.9 ± 7.5%; 31 with pacemakers at baseline) and no histories of heart failure or ventricular tachycardia were prospectively evaluated. Global longitudinal strain (GS), global systolic strain rate (GSRs), and global early diastolic strain rate (GSRe) of the right ventricle were measured using speckle tracking from apical views and compared with standard parameters of RV function (fractional area change, tricuspid annular plane systolic excursion, tissue Doppler velocities, and isovolumic acceleration) for association with and potential prediction of clinical events, defined as incident stage C heart failure or ventricular tachycardia. Results Baseline RV GS, GSRs, and GSRe were −12.5 ± 3.0%, −0.59 ± 0.14 sec −1 , and 0.68 ± 0.22 sec −1 , respectively. After a median of 2.4 years (interquartile range, 1.5–4.1 years), 12 patients (19%) presented with clinical events (heart failure in 11 patients, ventricular tachycardia in one patient). In Cox models, RV GS had the strongest association with clinical events (hazard ratio [HR] per 1%, 1.35; 95% confidence interval [CI], 1.14–1.58; P −1 , 1.06; 95% CI, 1.02–1.11; P = .006), GSRe (HR per −0.01 sec −1 , 1.04; 95% CI, 1.00–1.07; P = .031), and fractional area change (HR per −1%, 1.08; 95% CI, 1.00–1.17; P = .047). Other measures of RV function were not significantly associated with risk for events. In receiver operating characteristic analysis, RV GS ≥ −10% optimally predicted future events (C = 0.83; 95% CI, 0.71–0.91; P Conclusions Reduced longitudinal GS of the systemic right ventricle is associated with increased risk for clinical events among patients with D-transposition of the great arteries and prior atrial switch.

A 15-year-old post-neonatal repair of truncus arteriosus sustained an anterior leaflet mitral valve injury during elective aortic root replacement and aortic valve repair, resulting in severe mitral regurgitation ([Figure 1][1], [Online Video 1][2]). He was deemed not to be a surgical candidate in

Background Twin-twin transfusion syndrome (TTTS) complicates 10% to 15% of monochorionic twin pregnancies. Cardiovascular changes of variable severity, such as ventricular hypertrophy, atrioventricular valve regurgitation, and systolic dysfunction, occur predominantly in recipient twins (RTs). It was the purpose of this study to perform a detailed assessment of ventricular geometry and diastolic function between controls, donor twins (DTs), and RTs. Methods In this prospective, case-control study, two-dimensional, pulsed-wave, and Doppler tissue imaging were used to evaluate biventricular geometry and diastolic function in controls, DTs, and RTs. RTs were divided into two groups, severe and mild, on the basis of evidence of high central venous pressure. Specific variables evaluated included relative wall thickness, mitral valve and tricuspid valve E/A velocities, diastolic filling time corrected for heart rate, isovolumic relaxation time, and early (E′) and late (A′) diastolic myocardial velocities. Results A total of 120 fetuses (39 TTTS twin pairs and 42 controls) were compared. Increases in relative wall thickness and isovolumic relaxation time were seen in the mild group. In the severe group, further increases in relative wall thickness and isovolumic relaxation time as well as decreased diastolic filling time corrected for heart rate were accompanied by the appearance of a monophasic Doppler inflow profile and elevations in the E/E′ ratio, consistent with elevated ventricular filling pressures. Conclusions Concentric hypertrophy is observed in RTs affected by TTTS and is associated with impaired ventricular relaxation and shortened filling time. In severe cases, further decreases in diastolic filling time and Doppler signs of elevated ventricular filling pressures are present.

Background: The favorable outcomes of Eisenmenger syndrome (ES) relative to other forms of pulmonary arterial hypertension (PAH) have been partially attributed to a unique adaptation of the right ventricle (RV). However, conventional measures of RV function may not adequately express this adaptation. Methods: We studied 23 patients with ES (age 43 ± 17 years, 16 women, pulmonary artery systolic pressure [PASP] 93 ± 26 mmHg), 25 patients with PAH (age 44 ± 13 years, 17 women, PASP 92 ± 19 mmHg), and 25 subjects without known structural disease (age 45 ± 16 years, 17 women). We evaluated long- and short-axis function of the RV with two-dimensional strain and anatomical M-mode echocardiography, respectively. Results: Long-axis function of the RV was comparable between patients with ES and PAH although depressed relative to controls (global strain, −15.6 ± 4.7, −14.9 ± 4.3, and −22.4 ± 2.8%, respectively, P < 0.001; global RV systolic strain rate, −0.77 ± 0.26, −0.84 ± 0.24, and −1.11 ± 0.21 1/sec, respectively, P < 0.001). However, short-axis RV function was significantly better in patients with ES versus those with PAH and preserved relative to controls (RV fractional shortening by anatomical M-mode, median [interquartile range], 21%[14–33%], 14%[10–16%], and 26%[22–36%], respectively, P = 0.002 for ES vs. PAH, P = 0.09 for ES vs. controls). This differential was not reflected in conventional measures of RV function (fractional area change, 32 ± 10 vs. 29 ± 8% in ES and PAH, respectively, P = 0.26). Conclusion: In patients with ES, the RV is characterized by preserved short-axis function, despite a depressed long-axis function. Thus, conventional assessment of RV function might not be suitable for patients with ES. (Echocardiography 2010;27:937-945)

Objective. Aortic arch recoarctation is responsible for significant morbidity and mortality after the Norwood Stage I procedure. Cuff blood pressure (BP) gradients and echocardiographic Doppler gradients are routinely used as noninvasive screening tests for early detection, but accuracy has not been systematically tested. We sought to evaluate the ability of cuff BP and Doppler gradients, measured at routine outpatient clinic visits, to predict significant arch obstruction in single ventricle patients after the Norwood operation. Design. Consecutive patients who underwent Norwood operation at our institution were identified retrospectively. Cuff and echocardiographic gradients measured prior to the pre-Glenn catheterization were compared to peak-to-peak systolic neoaortic arch gradients obtained at catheterization. Statistical analyses, including Receiver Operator Characteristic (ROC) curves, were performed using different cutpoints for cuff and echocardiographic gradients, evaluating their ability to predict a clinically significant catheter gradient. Results. Data were obtained in 68 patients. Echocardiographic gradient cutpoints were more sensitive but less specific than cuff BP gradient cutpoints at detecting a catheter gradient ≥ 10 mm Hg. Echo gradients ≥ 20 mm Hg showed 85% sensitivity and 95% specificity in detecting a systolic catheter gradient ≥ 10 mm Hg. Conclusion. Echocardiographic Doppler outperforms cuff BP as a sensitive noninvasive screening tool for early detection of significant arch obstruction in infants after the Norwood operation.

Previous studies have identified an increased incidence of bicuspid aortic valve (BAV) in patients with ventricular septal defect (VSD). Because endocardial cushion remodeling contributes to both the formation of semilunar valves and ventricular septation, we hypothesized that examination of humans with BAV and VSD would identify a specific VSD type. We evaluated VSD type in pediatric patients diagnosed with BAV and VSD (n=82) and compared findings to patients diagnosed with VSD and normal aortic valve morphology (n=429). VSD type was described as conoventricular, muscular, inlet or conoseptal using a clinical taxonomy. Based on the contribution of the outflow tract endocardial cushions to the membranous ventricular septum, we expected patients with BAV to have conoventricular VSD. In both patient groups, conoventricular VSD was most common; however, the prevalence was not significantly different when BAV patients were compared to those with normal aortic valve morphology (67% vs. 57%, p=0.11). The primary finding of this study is that despite a developmental link between semilunar valve formation and ventricular septation during cardiogenesis, there is no clear association between BAV and VSD type. This may be due to phenotypic and genetic heterogeneity of BAV and VSD, other modifying factors as manifested by differences in associated CVM, as well as limitations of the clinical taxonomy of VSD.

Background The aim of this study was to assess the relationship between cardiomyopathy and recipient twin (RT) outcome in twin-twin transfusion syndrome (TTTS). Methods Fetal echocardiography and outcomes data in 62 consecutive pregnancies with TTTS were reviewed. The primary outcome was neonatal RT survival. The severity of RT cardiomyopathy at presentation was assessed by the cardiovascular profile score (CVPS). RT outcomes and odds of survival were compared between groups stratified by CVPS. Results Overall neonatal survival for all fetuses was 61% (76 of 124). RT survival was 58% (36 of 62). Grouped by CVPS, RT survival was greater (50%) for those with CVPS ≥ 9 and even higher (74%) for CVPS of 10. Among the components of the CVPS, atrioventricular valve regurgitation was associated with negative RT outcome. Other factors at presentation were not predictive of RT outcome. Conclusions A normal CVPS in the RT in TTTS is predictive of improved survival compared with an abnormal CVPS, even in RTs with minor deductions. Standard clinical staging did not predict outcome. Cardiac assessment by CVPS may improve clinical decision making and the timing of fetal interventions.

OBJECTIVES This study evaluated the aerobic capacity, exercise capacity, and arterial oxygen saturation (O(2)Sat) in children before and after transcatheter Fontan fenestration closure. DESIGN Observational study comparing exercise parameters and hemodynamics before and after transcatheter fenestration closure in Fontan patients. OUTCOME MEASURES Working capacity, exercise duration, oxygen consumption (VO(2)), and arterial O(2)Sat were evaluated during aerobic exercise. RESULTS Twenty patients (mean age 11.4 years) underwent standardized exercise testing before and after fenestration closure. Twelve patients underwent cycle ergometry testing (mean age 14.8 years) (group 1), and eight younger patients (mean age 6.4 years) underwent Bruce treadmill testing (group 2). The same exercise protocol was used in each patient before and after fenestration closure (interval between tests: 118 +/- 142 days). Immediately following fenestration closure at cardiac catheterization, cardiac index decreased (3.0 to 2.1 L/minute/m(2)) and Fontan pressure increased (11 +/- 2 to 12 +/- 2 mm Hg) with an increased arterial saturation (92 to 96%) (P < .001). The total group demonstrated no significant change in pre- and postclosure maximal heart rates (164 +/- 21 and 169 +/- 19 bpm). Rest and exercise O(2)Sat increased (89 and 82 to 95 and 92%) (P < .0001). Exercise duration increased (7.7 +/- 1.9 to 9.2 +/- 2.4 minutes) (P < .0005). Maximal VO(2), indexed maximal VO(2), and total working capacity in kilopond-meters (kpm) increased (1.2 +/- 0.5, 27 +/- 7 and 2466 +/- 1012 to 1.3 +/- 0.4 L/minute, 31 +/- 9 mL/kg/minute and 2869 +/- 1051 kpm, respectively) (P < .005). CONCLUSION In children with a univentricular heart after Fontan palliation, transcatheter fenestration closure improves exercise arterial O(2)Sat and aerobic capacity despite a restricted resting cardiac output documented by catheterization immediately after the closure procedure.

OBJECTIVE. Diastolic runoff in the abdominal aorta, with subsequent circulatory mesenteric insufficiency, has been postulated as a cause of necrotizing enterocolitis in term infants with congenital heart disease. With this study we sought to determine whether Doppler-flow characteristics in the abdominal aorta can predict which infants are at specific risk, independent of gestational age and type of congenital heart disease. PATIENTS AND METHODS. We conducted a case-control study of term infants with congenital heart disease and proven necrotizing enterocolitis (n = 18) compared with gestational age–matched and diagnosis-matched control subjects (n = 20). Abdominal aortic Doppler velocities, time intervals, and reversals were analyzed. Groups were compared, and independent risk factors for necrotizing enterocolitis were determined. RESULTS. The groups were similar with regard to weight, pulse pressure, use of prostaglandins or inotropes, presence of a patent ductus arteriosus, and systolic function. However, 47% of the case subjects with necrotizing enterocolitis had persistent retrograde diastolic flow in the abdominal aorta compared with 15% of the control subjects. When adjusting for multiple risk factors, persistent diastolic flow reversal remained the only factor significantly associated with necrotizing enterocolitis. CONCLUSION. Persistent diastolic flow reversal in the abdominal aortic Doppler profile is associated with an increased risk of necrotizing enterocolitis in term infants with congenital heart disease irrespective of gestational age or anatomic type of congenital heart disease.

Objectives To examine cardiac structural and functional changes in twin–twin transfusion syndrome (TTTS), relative to Quintero stage, as a means of evaluating the spectrum of cardiomyopathy in TTTS. Methods This was a cross-sectional, retrospective study of 42 consecutive cases of TTTS referred to a single fetal therapy center. Quintero stages were assigned by standard criteria. Presence of ventricular hypertrophy, cardiomegaly, atrioventricular valve regurgitation (AVVR), ventricular systolic dysfunction and right ventricular outflow tract obstruction on fetal echocardiography were noted. The Doppler myocardial performance index (MPI), an index of global ventricular function, was calculated for both ventricles in subjects with adequate Doppler data. We compared cardiac changes across Quintero stages. Results There was no cardiomyopathy observed in donor twins. The majority of subjects presented at Quintero Stage I (n = 14), II (n = 14) or III (n = 11), with fewer at Stages IV (n = 2) or V (n = 1). As early as Quintero Stages I and II, a significant proportion of recipient twins had ventricular hypertrophy (17/28, 61%), AVVR (6/28, 21%) or quantitative abnormalities in either right (12/24, 50%) or left (14/24, 58%) ventricular function. Increasing prevalence of biventricular systolic dysfunction and cardiomegaly accompanied advancing Quintero stage. Conclusions Changes in cardiac structure and function not reflected in Quintero staging occur in recipient twins early in the evolution of TTTS. Incorporation of cardiac findings into assessment of TTTS severity may prove useful in stratification of risk and treatment selection. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.

Background The prenatal diagnosis of coarctation of aorta (CoA) can prove problematic, with relatively high false-positive and false-negative rates. This significantly impacts both prenatal counseling and postnatal management. We sought to evaluate a variety of prenatal echo indices to determine which would best predict neonatal CoA. Methods Fetal echocardiograms of those with prenatal diagnosis of COA were analyzed for the following: diameter of cardiac valves, ascending aorta, distal transverse arch, aortic isthmus, and ductus; right (RV) and left ventricular (LV) length and end-diastolic area and isthmus–ductal angle (IDA). Ratios of RV: LV area, aortic: pulmonary valve diameter, mitral: tricuspid valve ratio (MV:TV ratio), and isthmus: ductal diameter (IDD) were calculated. These measures were compared between those with CoA after birth (CoA group) and those without (no CoA group). Results Of the 62 subjects, 27 were in CoA and 35 in no CoA group. CoA group had a significantly smaller mitral valve, MV:TV ratio, IDD, and IDA compared to no CoA group. The ROC curves for each of these significant measures showed that mitral valve, IDD, and IDA had an AUC of 0.72, 0.80, and 0.83, respectively. Multiple variable model using at least two of these measures had 85% sensitivity and 60% specificity. Conclusions A smaller mitral valve, MV:TV ratio, IDD, and IDA are associated with development of neonatal coarctation. In cases with suspected prenatal diagnosis of CoA, careful evaluation of the relation between the isthmus and the ductus arteriosus using IDD and IDA may enhance the diagnostic accuracy of fetal echocardiograms.

Background Management of infants with heterotaxy syndrome and functional single ventricle is complicated due to associated cardiac and extracardiac anomalies. We report current era palliation results. Methods Between 2002 and 2012, 67 infants with heterotaxy syndrome underwent multistage palliation. Competing risks analyses modeled events after surgery (death vs Glenn procedure) and examined factors associated with survival. In addition, early and late outcomes following first-stage palliation surgery were compared with a matched contemporaneous control group of patients with nonheterotaxy single ventricle anomalies. Results Fifty-eight patients (87%) required neonatal palliation, including a modified Blalock-Taussig shunt (n = 34; 51%), Norwood operation (n = 12; 18%) or pulmonary artery band (n = 12; 18%), whereas 9 patients (13%) underwent a primary Glenn procedure. Competing risks analysis showed that at 1 year after first-stage palliation surgery, 29% of the patients had died or undergone transplantation and 63% had undergone a Glenn procedure. By 5 years after the Glenn procedure, 64% of patients had undergone a Fontan procedure. The overall 8-year survival rate was 66%. On multivariable analysis, factors associated with mortality were unplanned reoperation (hazard ratio [HR], 2.9; 95% confidence interval [CI], 1.1-7.3; P = .005) and total anomalous pulmonary venous connection repair (HR, 2.3; 95% CI, 1.0-5.6; P = .056). Comparison with the contemporaneous matched patients with nonheterotaxy single ventricle anomalies showed that first-stage palliation in the patients with heterotaxy was associated with a higher rate of in-hospital death (27% vs 10%; P = .022), and significantly longer durations of ventilation and intensive care unit stay. Interstage mortality, survival after the Glenn procedure, and progression to the Fontan procedure were comparable in the 2 groups. Conclusions The management of infants with heterotaxy and a functional single ventricle remains challenging. First-stage palliation is associated with high operative mortality and increased resource utilization owing to surgical morbidity. Nonetheless, outcomes beyond hospital discharge are comparable to those for patients with other single ventricle anomalies. Efforts to improve survival in those patients should focus on perioperative care.

Stress echocardiography is a well-established technique in adult cardiology and is mainly used for assessing regional myocardial function in patients with known or suspected coronary artery disease (CAD). Apart from detecting ischaemia, stress echocardiography has found its place in the assessment of the haemodynamic significance of valve disease, particularly in selected patients with aortic stenosis and mitral regurgitation. Also in the paediatric population, stress imaging is most commonly used for the detection of ischaemia in patients with CADs such as post heart transplantation, Kawasaki Disease, and abnormal origin of coronary arteries. Other paediatric indications include the haemodynamic and myocardial response in patients with different types of congenital heart disease, the early detection of myocardial dysfunction in specific populations such as patients after anthracycline exposure, and the evaluation of pulmonary artery pressures and the right ventricular functional response. Techniques have evolved over time and in different paediatric echocardiographic laboratories, exercise stress echocardiography is replacing dobutamine stress echocardiography in older children. Moreover, intergrating tissue Doppler and strain technology with stress imaging allows a more quantitative analysis of regional and global systolic and diastolic function. Current clinical applications mainly include patients after transplant, suspected CAD, and hypertrophic cardiomyopathy.

Background— Pulmonary venous Doppler (PVD) flow patterns in the fetus with hypoplastic left heart syndrome (HLHS) have been correlated with restrictive interatrial communication or intact atrial septum (RAS) postnatally; however, the ability of PVD to identify the neonate requiring emergent atrial septoplasty (EAS) for severe left atrial hypertension and hypoxemia has not been critically evaluated. It was the purpose of this study to determine the predictive power of fetal PVD in identifying the need for EAS in newborns with HLHS and RAS. Methods and Results— Forty-one patients with fetal PVD flow analysis and postnatally confirmed HLHS were studied. Pulsed-wave assessment of PVD flow included S-, D-, and A-wave velocity, time-velocity integral (VTI) of forward and reverse flow, and S/D velocity and forward/reverse VTI ratio. Neonatal EAS was used as the primary clinical outcome variable. Receiver operating characteristic curves were used to determine cutpoints at which PVD indices best predicted EAS. Cutpoints were evaluated for clinical accuracy and usefulness by use of Bayesian analysis. Eight of 41 subjects underwent EAS. Need for EAS was most accurately predicted by forward/reverse VTI ratio Conclusions— In the fetus with HLHS, a PVD forward/reverse VTI ratio of

The purpose of this study was to explore the validity of diastolic indices derived from color M-mode Doppler and Doppler tissue imaging in a heterogeneous group of pediatric patients by comparing them with simultaneously obtained invasive indices of diastolic function.A total of 20 children undergoing left heart catheterization had echocardiographic images recorded simultaneously with high-fidelity left ventricular (LV) pressure tracings. Transmitral Doppler, pulmonary vein Doppler, Doppler tissue imaging, and color M-mode Doppler flow propagation velocity were recorded. LV peak negative dP/dt, the time constant of isovolumic relaxation, and LV end-diastolic pressure were compared with the echocardiographic indices.The ratio of peak E-wave mitral velocity/propagation velocity correlated significantly with LV end-diastolic pressure (r = 0.71; P.001). Propagation velocity correlated with the time constant of isovolumic relaxation (r = -0.56; P =.01) and peak negative dP/dt (r = 0.50; P.03). Septal mitral annular myocardial velocity correlated significantly with the time constant of isovolumic relaxation (r = -0.58, P =.01).The newer diastolic indices derived from color M-mode Doppler and Doppler tissue imaging appear to be a helpful adjunct in the noninvasive assessment of diastolic function in children.

Background. Pancreatitis following cardiopulmonary bypass is a well-known complication in adults undergoing cardiac surgery. However, the occurrence of pancreatitis in pediatric patients undergoing repair of congenital heart disease is under-appreciated. Post-Fontan patients are particularly prone to postoperative pancreatitis. In an effort to identify specific perioperative factors predictive of postoperative pancreatitis, we retrospectively reviewed a group of Fontan patients. Methods. From June 1996 to June 2001, 40 patients underwent a modified Fontan operation. Four patients developed acute pancreatitis postoperatively. The preoperative, intraoperative, and postoperative hemodynamics and ventricular function parameters were retrospectively analyzed and compared to 10 randomly selected Fontan patients who did not have pancreatitis. Preoperative echocardiographic and angiographic data, including digitized ventricular pressure tracings, were reviewed to obtain ventricular relaxation time constant (tau), pulmonary vascular resistance (PVR), ventricular end diastolic pressure (VEDP), positive dp/dt and negative dp/dt values. Results. Patients developing acute pancreatitis had very high mortality (50%) compared to no mortality in the control group. The mean preoperative tau was significantly prolonged (41 ms vs 26 ms in control group, p < 0.001), and pre operative systemic output (Qs) lower in the pancreatitis group (mean 2.75 L/min/m 2 ) compared with controls (Qs of 5.09 L/min/m 2 , p < 0.03). Conclusions. Impaired ventricular relaxation and decreased preoperative cardiac output are predictive of increased risk of postoperative pancreatitis in Fontan patients. Evaluation of preoperative diastolic function in these patients may provide additional insights in to clinical outcome following the Fontan procedure.

Background: The role of tricuspid annular plane systolic excursion (TAPSE) in evaluating right ventricular (RV) function in hypoplastic left heart syndrome (HLHS) has not been fully explored. We sought to evaluate the relation between TAPSE and RV fractional area change (FAC) and cardiac index (CI)

Although elevated tricuspid regurgitant velocity (TRV), an echocardiographic marker for pulmonary hypertension, has previously been tied to mortality in adult patients with sickle cell disease, recent data demonstrated that it correlates poorly with catheterization findings. We describe the largest echocardiographic evaluation of pediatric patients with sickle cell disease to date, specifically the results of a protocol whereby a TRV≥250 cm/s prompted further evaluation. We investigated if elevated TRV would independently identify patients at risk for increased morbidity. A clinical echocardiographic database containing 630 patients with sickle cell disease was retrospectively reviewed; 120 patients (19%) met inclusion criteria and were compared 1:1 to randomly selected age-matched controls from the same database. By multivariate analysis, the elevated TRV cohort did not differ from controls in likelihood of acute chest episodes, hospitalization, or stroke. The study cohort's mean TRV in fact decreased to 242±33 cm/s at follow-up without a discernible and comprehensive intervention to explain the improvement. Three patients had catheterization-proven pulmonary hypertension. In conclusion, elevated TRV in children with sickle cell disease is less prevalent than previously thought and is not independently associated with increased short-term morbidity.

Although the diagnostic criteria for acute rheumatic fever (ARF) are well known, a high index of suspicion is necessary in order to assure timely diagnosis and appropriate treatment. We present a case of an 8-year-old child who presented with unilateral pulmonary edema secondary to acute mitral insufficiency due to ARF. ARF should be considered in the differential diagnosis of unilateral pulmonary edema in children.

Sudden infant death syndrome (SIDS), a leading cause of infant death, have a disproportionate psychosocial and medicolegal impact because they usually occur in otherwise healthy babies. While many pathophysiologic mechanisms for SIDS have been proposed, including respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of metabolism, none has caused as much controversy as the cardiac dysrhythmia hypothesis. The existence of an association between SIDS and the long QT syndrome (LQTS) has been at the heart of this debate for over 30 years. In this issue of Heart Rhythm, Cronk et al report the first molecular and functional evidence to implicate CAV3 as a pathogenic basis of SIDS [1]; how does this elegant study fit into the controversy?

A Pediatric Heart Network trial compared outcomes in infants with single right ventricle anomalies undergoing Norwood procedures randomized to modified Blalock-Taussig shunt (MBTS) or right ventricle-to-pulmonary artery shunt (RVPAS). Doppler patterns in the neo-aorta and RVPAS may characterize physiologic changes after staged palliations that affect outcomes and right ventricular (RV) function.Neo-aortic cardiac index (CI), retrograde fraction (RF) in the descending aorta and RVPAS conduit, RVPAS/neo-aortic systolic ejection time ratio, and systolic/diastolic (S/D) ratio were measured early after Norwood, before stage II palliation, and at 14 months. These parameters were compared with transplantation-free survival, length of hospital stay, and RV functional indices.In 529 subjects (mean follow-up period, 3.0 ± 2.1 years), neo-aortic CI and descending aortic RF were significantly higher in the MBTS cohort after Norwood. The RVPAS RF averaged25% at both interstage intervals. Higher pre-stage II descending aortic RF was correlated with lower RV ejection fraction (R = -0.24; P = .032) at 14 months for the MBTS cohort. Higher post-Norwood CI (5.6 vs 4.4 L/min/m(2), P = .04) and lower S/D ratio (1.40 vs 1.68, P = .01) were correlated with better interstage transplantation-free survival for the RVPAS cohort. No other Doppler flow patterns were correlated with outcomes.After the Norwood procedure, infants tolerated significant descending aortic RF (MBTS) and conduit RF (RVPAS), with little correlation with clinical outcomes or RV function. Neo-aortic CI, ejection time, and S/D ratios also had limited correlations with outcomes or RV function, but higher post-Norwood neo-aortic CI and lower S/D ratio were correlated with better interstage survival in those with RVPAS.

Background Guidelines published by the Children's Oncology Group recommend screening echocardiograms for childhood cancer survivors exposed to anthracyclines and/or cardiotoxic radiation. This study aims to assess risk factors for cardiac late effects while evaluating the overall yield of screening echocardiograms. Procedure Demographics, exposures, and echocardiogram results were abstracted from the medical records of survivors diagnosed at ≤ 21 years old and ≥ 2 years off therapy who were exposed to anthracyclines and/or potentially cardiotoxic radiotherapy. Descriptive statistics and logistic regressions were performed and the yield of screening echocardiograms was calculated. Results Of 853 patients, 1,728 screening echocardiograms were performed, and 37 patients had an abnormal echocardiogram (overall yield 2.1%). Yields were only somewhat higher in more frequently screened patients. Risk factors for an abnormal result included anthracycline dose of ≥300 mg/m2 (adjusted odds ratio [aOR] 3.1; 95% confidence interval [CI]: 1.3−7.2; P < 0.01) with a synergist relationship in patients who also received radiation doses ≥30 Gy (aOR 7.0; 95% CI: 1.6–31.9; P = 0.01), as well as autologous bone marrow transplant (OR 3.3; 95% CI: 1.3–8.5; P = 0.01). Sex, race, age at diagnosis, and cyclophosphamide exposure were not statistically significant risk factors, and no patient receiving

Background Left ventricular outflow tract obstruction (LVOTO) is an important problem after interrupted aortic arch (IAA) repair, especially when early reoperation is required during infancy. Several anatomic factors have been identified that increase LVOTO risk; surgical strategies such as concomitant resection of the conal septum or left ventricular outflow tract (LVOT) bypass (single-stage Yasui operation, or staged Norwood procedure, followed by the Rastelli procedure) have been proposed for such patients. Methods From 2002 to 2013, a total of 77 neonates underwent IAA repair. Based on the presence of anatomic substrate for LVOTO, patients underwent standard IAA repair and ventricular septal defect closure (n = 53; 69%), concomitant conal resection (n = 7; 9%), or LVOT bypass (n = 17; 22%, staged in 14). We analyzed anatomic details that influence procedure choice, and explored reoperation risk and survival after repair. Results Neonates who had conal resection or LVOT bypass had significantly smaller aortic valve and subaortic areas, as well as a trend toward a higher prevalence of type B IAA, aberrant right subclavian artery, and bicuspid aortic valve. Freedom from LVOT reoperation was 96% and 80%, at 1 and 8 years, respectively, and was lower after conal resection ( P = .008). Most LVOT reoperations (73%) were for discrete subaortic obstruction. Survival was 86% at 8 years, and was not related to procedure choice, whereas freedom from all-cause reoperation was 65% at 8 years, and was higher after standard repair ( P = .029). Conclusions Compared with published reports, this selective management strategy, which is customized to the degree of aortic valve and subaortic area narrowing, has mitigated and delayed LVOTO risk. With this tailored approach, most LVOT reoperations occur after infancy and are commonly for discrete subaortic obstruction. The effect of aortic valve and LVOT narrowing on increased LVOTO risk is neutralized with LVOT bypass procedures; however, it continues to be the highest after conal resection, suggesting the superiority of LVOT bypass, compared with enlargement in neonates who are at risk of developing LVOTO.

Persistent pressure overload can cause cardiac hypertrophy and progressive heart failure (HF). The authors developed a pressure-overload HF model of juvenile mice to study the cardiac response to pressure overload that may be applicable to clinical processes in children. Severe thoracic aortic banding (sTAB) was performed using a 28-gauge needle for 40 juvenile (age, 3 weeks) and 47 adult (age, 6 weeks) C57BL/6 male mice. To monitor the structural and functional changes, M-mode echocardiography was performed for conscious mice that had undergone sTAB and sham operation. Cardiac hypertrophy, dilation, and HF occurred in both juvenile and adult mice after sTAB. Compared with adults, juvenile HF is characterized by greater impairment of ventricular contractility and less hypertrophy. In addition, juvenile mice had significantly higher rates of survival than adult mice during the early postoperative weeks. Consistent with clinical HF seen in children, juvenile banded mice demonstrated a lower growth rate than either adult banded mice or juvenile control mice that had sham operations. The authors first developed a juvenile murine model of pressure-overload HF. Learning the unique characteristics of pressure-overload HF in juveniles should aid in understanding age-specific pathologic changes for HF development in children.

Background— Angiotensin-converting enzyme inhibitor therapy improves clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology have poor growth and are at risk for abnormalities in ventricular systolic and diastolic function. The ability of angiotensin-converting enzyme inhibitor therapy to preserve ventricular function and improve somatic growth and outcomes in these infants is unknown. Methods and Results— The Pediatric Heart Network conducted a double-blind trial involving 230 infants with single-ventricle physiology randomized to receive enalapril (target dose 0.4 mg · kg −1 · d −1 ) or placebo who were followed up until 14 months of age. The primary end point was weight-for-age z score at 14 months. The primary analysis was intention to treat. A total of 185 infants completed the study. There were 24 and 21 withdrawals or deaths in the enalapril and placebo groups, respectively ( P =0.74). Weight-for-age z score was not different between the enalapril and placebo groups (mean±SE −0.62±0.13 versus −0.42±0.13, P =0.28). There were no significant group differences in height-for-age z score, Ross heart failure class, brain natriuretic peptide concentration, Bayley scores of infant development, or ventricular ejection fraction. The incidence of death or transplantation was 13% and did not differ between groups. Serious adverse events occurred in 88 patients in the enalapril group and 87 in the placebo group. Conclusions— Administration of enalapril to infants with single-ventricle physiology in the first year of life did not improve somatic growth, ventricular function, or heart failure severity. The results of this randomized trial do not support the routine use of enalapril in this population. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00113087.

Background The purpose of this study was to identify factors predicting risk of aortic arch recoarctation after the Norwood procedure. Methods Patient records were reviewed retrospectively for consecutive patients who underwent the Norwood procedure from 1996 to 2005. Preoperative and intraoperative parameters were identified for analysis. Aortic arch recoarctation was defined by the need for catheter or surgical reintervention. Data were analyzed using survival analysis, with freedom from intervention as the outcome. Factors predicting need for reintervention were analyzed using Cox proportional hazards regression. Results Thirty-five recoarctations were observed in 117 patients (30%). Freedom from aortic arch reintervention at six months, one, three, and five years were 72%, 63%, 56%, and 52%, respectively. The majority of arch reinterventions occurred in the first six months (63%), involving either surgical (43%) or catheter (57%) techniques. The use of bovine pericardium showed the greatest risk for potential recoarctation (hazard ratio=1.81 [0.90–3.64], p = 0.09). Age, gender, weight, ascending aortic diameter, ventricular morphology, primary anatomic diagnosis, and coarctation shelf resection were not found to be predictors of recoarctation. Conclusions Most interventions for aortic arch recoarctation after the Norwood procedure occur within the first six months of life. The type of patch material used for arch reconstruction appears to influence, most strongly, the long-term risk of aortic arch recoarctation.

Objective To evaluate whether essential hypertension impacts diastolic function in children. Study design In this cross-sectional study, patients with essential hypertension (n = 50) were compared with a normotensive group (n = 53). Echocardiographic assessment of diastolic function included measures derived from transmitral, color M-mode, and tissue Doppler interrogation. Cardiac dimensions, wall thickness, geometry, and systolic function were also assessed. Multiple linear regression analysis was performed to identify predictors of altered diastolic function. Results Diastolic filling abnormalities were found in 36% of the children with blood pressure elevation. Those subjects with concentric hypertrophy were more significantly affected. Abnormalities in indices reflective of left ventricular (LV) relaxation occurred more commonly (39%) than those of LV compliance (33%). Elevated indexed LV mass was found to be the most significant independent predictor of diastolic filling abnormalities. Conclusions LV diastolic filling abnormalities were found in one-third of the pediatric subjects with essential hypertension. Whether these changes represent an adaptive or maladaptive response requires further study.