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As part of a clinical trial, this study examined the pharmacokinetics (PK) of oral treprostinil (TRE) in children with pulmonary arterial hypertension. The trial consisted of the following 3 cohorts: transition from parenteral (cohort 1) or inhaled (cohort 2) TRE, or de novo addition (cohort 3). Oral TRE was dosed 3 times daily. PK samples were obtained before an oral TRE dose, and at 2, 4, 6, and 8 hours thereafter. The PK parameters were calculated using noncompartmental analysis. Thirty-two children (n = 10 in cohorts 1 and 2, n = 12 in cohort 3) were enrolled; the median age was 12 years (range 7-17 years), and the median weight was 42.2 kg (range 19.3-78 kg). The median oral TRE dose for all subjects was 3.8 mg (5.9, 3.5, and 4.0 mg for cohorts 1, 2, and 3, respectively). The TRE concentration versus time profile demonstrated a peak concentration at a median of 3.8 hours with wide variability. In cohort 1, oral dosing led to higher peak (5.9 ng/mL) and lower trough (1 ng/mL) concentrations than parenteral (peak 5.4 ng/mL and trough 4.2 ng/mL), but a lower mean concentration (3.61 vs. 4.46 ng/mL), likely due to variable metabolism and noncomparable dosing. Both the area under the curve and average concentration were linearly correlated with oral TRE dose and dose normalized to body weight, but not with weight or age alone. In pediatric patients, an increased oral TRE dose or dose frequency may be required to minimize PK variability and achieve greater correlation with parenteral dosing.

Purpose: To evaluate the physical and chemical compatibilities of treprostinil sodium and dopamine hydrochloride., Methods: Treprostinil sodium (4,000, 76,000, and 500,000 ng/mL) were mixed with dopamine hydrochloride (0.6, 3.2, 6, and 40 mg/mL). Samples were obtained at hours 0, 1, 2, and 4 for physical compatibility and chemical stability testing. Physical compatibility was assessed by visual examination and measurements of turbidity and pH. Drug concentrations were assessed using stability-indicating liquid chromatography mass spectrophotometry (LCMS) for treprostinil sodium and stability-indicating high-performance liquid chromatography (HPLC) for dopamine hydrochloride., Results: Treprostinil sodium 4,000 and 76,000 ng/mL, when mixed with dopamine hydrochloride 0.6, 3.2, 6, and 40 mg/mL, were stable for 4 hours. Treprostinil sodium 500,000 ng/mL was stable when mixed with dopamine hydrochloride 0.6 mg/mL for 4 hours, but when mixed with dopamine hydrochloride 3.2, 6, and 40 mg/mL, significant precipitation was seen., Conclusion: Treprostinil sodium 4,000 and 76,000 ng/mL were stable for 4 hours during simulated Y-site coadministration with dopamine hydrochloride 0.6, 3.2, 6, and 40 mg/mL. Treprostinil sodium 500,000 ng/mL is stable when mixed with dopamine hydrochloride 0.6 mg/mL., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although elevated right ventricular pressure and left ventricular diastolic dysfunction measured by echocardiogram are independent predictors of death in adults with sickle cell disease (SCD), the utility of routine echocardiographic screening in the pediatric population is controversial. We performed a 3-year retrospective review of children ≥ 10 years of age with SCD who underwent an outpatient transthoracic echocardiogram as part of a screening program. Of 172 patients referred for screening, 105 (61%) had a measurable tricuspid regurgitation jet velocity (TRV): median 2.4 m/s (IQR 2.3-2.5). Elevated right ventricular (RV) pressure (TRV ≥ 2.5 m/s, 25 mmHg), documented in 30% (32/105), was significantly associated with chronic transfusion therapy and elevated lactate dehydrogenase. Left ventricle (LV) dilation, documented in 25% (44/172), was significantly associated with lower hemoglobin, and higher reticulocyte count, lactate dehydrogenase level, and bilirubin level. There was no association between elevated right ventricular pressure or left ventricle dilation and indices of biventricular systolic or diastolic function. The one death in the cohort during the study period had normal echocardiographic findings. In conclusion, mild RV pressure elevation and LV dilation in children with SCD is associated with abnormal laboratory markers of disease severity, but not with ventricular dysfunction over the 3-year study period.

Background/purpose: Prostaglandin E1 (PGE) has been used to maintain ductus arteriosus patency and unload the suprasystemic right ventricle (RV) in neonates with congenital diaphragmatic hernia (CDH) and severe pulmonary hypertension (PH). Here we evaluate the PH response in neonates with CDH and severe PH treated with PGE., Methods: We performed a retrospective chart review of CDH infants treated at our center between 2011 and 2016. In a subset, PGE was initiated for echocardiographic evidence of severe PH, metabolic acidosis, or hypoxemia. To assess PH response, we evaluated laboratory data, including B-type natriuretic peptide (BNP) and echocardiograms before and after PGE treatment. Categorical and continuous data were analyzed with Fisher's exact tests and Mann-Whitney t-tests, respectively., Results: Fifty-seven infants were treated with PGE a mean 17 ± 2 days. BNP levels declined after 1.4 ± 0.2 days of treatment and again after 5.2 ± 0.6 days. After 6 ± 0.8 days of treatment, echocardiographic estimates of severe PH by tricuspid regurgitation jet velocity, ductus arteriosus direction, and ventricular septum position also improved significantly. Treatment was not associated with postductal hypoxemia or systemic hypoperfusion., Conclusions: In patients with CDH and severe PH, PGE is well tolerated and associated with improved BNP and echocardiographic indices of PH, suggesting successful unloading of the RV., Type of Study: Treatment study., Level of Evidence: Level III., (Copyright © 2018. Published by Elsevier Inc.)

While pulmonary hypertension (PH) is a potentially life threatening complication of many inflammatory conditions, an association between Aicardi Goutières syndrome (AGS), a rare genetic cause of interferon (IFN) overproduction, and the development of PH has not been characterized to date. We analyzed the cardiac function of individuals with AGS enrolled in the Myelin Disorders Bioregistry Project using retrospective chart review (n = 61). Additional prospective echocardiograms were obtained when possible (n = 22). An IFN signature score, a marker of systemic inflammation, was calculated through the measurement of mRNA transcripts of type I IFN-inducible genes (interferon signaling genes or ISG). Pathologic analysis was performed as available from autopsy samples. Within our cohort, four individuals were identified to be affected by PH: three with pathogenic gain-of-function mutations in the IFIH1 gene and one with heterozygous TREX1 mutations. All studied individuals with AGS were noted to have elevated IFN signature scores (Mann-Whitney p < .001), with the highest levels in individuals with IFIH1 mutations (Mann-Whitney p < .0001). We present clinical and histologic evidence of PH in a series of four individuals with AGS, a rare interferonopathy. Importantly, IFIH1 and TREX1 may represent a novel cause of PH. Furthermore, these findings underscore the importance of screening all individuals with AGS for PH., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To evaluate the effect of continuous treprostinil in infants with severe pulmonary hypertension associated with congenital diaphragmatic hernia (CDH) on specific markers of pulmonary hypertension severity and to report the safety and tolerability of treprostinil., Study Design: We conducted a retrospective cohort study of infants with CDH-associated pulmonary hypertension treated with treprostinil from January 2011 to September 2016. Severity of pulmonary hypertension was assessed by echocardiogram and serum B-type natriuretic peptide (BNP) by using time points before initiation and 24 hours, 1 week, and 1 month after treprostinil initiation. Fisher exact tests, Wilcoxon-rank sum tests, and mixed-effects models were used for analysis., Results: Seventeen patients were treated with treprostinil for a median of 54.5 days (IQR 44.3-110 days). Compared with the concurrent CDH population (n = 147), infants treated with treprostinil were more likely to require extracorporeal support (76.5% vs 25.2%, P < .0001), to have a longer hospital stay (144 vs 60 days, P < .0001), and to need longer mechanical ventilator support (76.5 vs 30.9 days, P < .0001). Following treprostinil initiation, there was a significant reduction in BNP at 1 week (1439 vs 393 pg/mL, P < .01) and 1 month (1439 vs 242 pg/mL, P = .01). Severity of pulmonary hypertension by echocardiogram improved at 1 month (OR 0.14, CI 95% 0.04-0.48, P = .002). Despite these improvements, overall mortality remained high (35%). There were no adverse events related to treprostinil, including no hypotension, hypoxia, or thrombocytopenia., Conclusions: In this cohort, treprostinil use was associated with improved severity of pulmonary hypertension assessed by echocardiogram and decreased BNP, with no significant side effects., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pulmonary hypertension (PH) causes significant morbidity and mortality in children due to right ventricular (RV) failure. We sought to determine the effect of prostacyclin analogues on RV function assessed by echocardiography in children with PH. We conducted a retrospective cohort study of children with PH treated with a prostacyclin analogue (epoprostenol or treprostinil) between January 2001 and August 2015 at our center. Data were collected before initiation of treatment (baseline) and at 1-3 and 6-12 months after. Protocolized echocardiogram measurements including tricuspid annular plane systolic excursion (TAPSE) and RV global longitudinal strain were made with blinding to clinical information. Forty-nine individuals (65% female), aged 0-29 years at the time of prostacyclin initiation were included. Disease types included pulmonary arterial hypertension (idiopathic [35%], heritable [2%], and congenital heart disease-associated [18%]), developmental lung disease (43%), and chronic thromboembolic PH (2%). Participants received intravenous (IV) epoprostenol (14%) and IV/subcutaneous (SQ) (67%) or inhaled (18%) treprostinil. Over the study period, prostacyclin analogues were associated with improvement in TAPSE ( P = 0.007), RV strain ( P < 0.001), and qualitative RV function ( P = 0.037) by echocardiogram, and BNP ( P < 0.001), functional class ( P = 0.047) and 6-min walk distance ( P = 0.001). TAPSE and strain improved at early follow up ( P = 0.05 and P = 0.002, respectively) despite minimal RV pressure change. In children with PH, prostacyclin analogues are associated with an early and sustained improvement in RV function measured as TAPSE and strain as well as clinical markers of PH severity. RV strain may be a sensitive marker of RV function in this population.

Hypertrophic cardiomyopathy has a range of clinical severity in children. Treatment options are limited, mainly on account of small patient size. Disopyramide is a sodium channel blocker with negative inotropic properties that effectively reduces left ventricular outflow tract gradients in adults with hypertrophic cardiomyopathy, but its efficacy in children is uncertain. A retrospective chart review of patients ⩽21 years of age with hypertrophic cardiomyopathy at our institution and treated with disopyramide was performed. Left ventricular outflow tract Doppler gradients before and after disopyramide initiation were compared as the primary outcome measure. Nine patients received disopyramide, with a median age of 5.6 years (range 6 days-12.9 years). The median left ventricular outflow tract Doppler gradient before initiation of disopyramide was 81 mmHg (range 30-132 mmHg); eight patients had post-initiation echocardiograms, in which the median lowest recorded Doppler gradient was 43 mmHg (range 15-100 mmHg), for a median % reduction of 58.2% (p=0.002). With median follow-up of 2.5 years, eight of nine patients were still alive, although disopyramide had been discontinued in six of the nine patients. Reasons for discontinuation included septal myomectomy (four patients), heart transplantation (one patient), and side effects (one patient). Disopyramide was effective for the relief of left ventricular outflow tract obstruction in children with hypertrophic cardiomyopathy, although longer-term data suggest that its efficacy is not sustained. In general, it was well tolerated. Further study in larger patient populations is warranted.

Right atrial (RA) mechanics have been studied infrequently in children in the past due to technical constraints. With the advent of strain imaging, RA physiology can now be studied in greater detail. The principal aim of this study was to describe functional changes in right heart mechanics of children with idiopathic pulmonary arterial hypertension (PAH), by using new applications of RA strain. In this retrospective study, we evaluated RA mechanics of 20 patients (age range = 3-23 years) with PAH and 18 control patients. RA longitudinal strain (RALS) and longitudinal displacement (LD) were calculated by speckle-tracking echocardiography. RALS was plotted against LD, producing a characteristic strain-displacement (S-D) loop. Standard indices of right heart function and right heart catheterization data were obtained. Patients were clinically subdivided into "compensated" and "decompensated" PAH. A chart review was performed to identify patients who subsequently developed adverse outcomes, including death, awaiting or received lung and/or heart transplantation. RALS was significantly lower in decompensated PAH compared with both controls and compensated PAH. Area enclosed by S-D loops differed significantly between the compensated and decompensated PAH subgroups (5.33 [3.90-9.44] versus 1.83 [1.17-2.36], P < 0.05). S-D loop area and RALS possessed high sensitivity and specificity compared to other parameters for identifying children with PAH who subsequently developed adverse outcomes. In particular, their sensitivities and specificities were greatly superior compared to those of tricuspid annular plane systolic excursion (TAPSE). RALS may represent a useful metric for assessing right ventricular (RV) dysfunction. S-D loops, composed over an entire cardiac cycle, may present useful, composite information regarding both systolic and diastolic right heart function. RA mechanics may serve as useful tools for identifying patients with more severe PAH, who are at risk for future adverse outcomes associated with RV failure.

Background: Telemedicine is a rapidly evolving form of modern information and communication technology used to deliver clinical services and educational activities., Objective: The aim of this article is to report and analyze our experience with transatlantic consultation via videoconferencing in pediatric cardiology., Methods: In February, 2013, videoconferencing project was launched between a medium-volume pediatric cardiac center in Bratislava, Slovakia and subspecialty experts from a high-volume pediatric cardiac program at The Children's Hospital of Philadelphia (CHOP), USA. During 1.5-2 hours videoconferences, 2-3 patients with similar complex clinical scenarios were presented to CHOP experts. The main goal of the project was consultation on individual patients to validate, alter or radically change clinical management plans., Results: From February, 2013 to January, 2017, 25 videoconferences occurred and 73 cases were discussed. The median patient age was 52 months (range; 1 day-30 years). Forty-six discussed cases were outpatients, 21 patients were in the intensive care unit and 6 patients were discussed post mortem. Thirty-one CHOP experts from different subspecialties participated actively in patient consultations. The most frequent recommendations were related to single ventricle, pulmonary hypertension or heart failure patients and intervention in complex and/or rare cardiac diseases. Specialists from CHOP agreed completely with the original care plan in 16% of cases. In 52% cases, adjustments to original plan were suggested. Radical changes were recommended in 30% of cases. Receiving institution adopted recommendations to the patient care fully in 79% and partially in 13% of patients., Conclusions: Based on our 4-year experience we consider videoconferencing between medium-size pediatric cardiac center and subspecialty experts from a high-volume pediatric cardiac program a suitable form of medical consultations. Videoconferencing assists in clinical decision making for complex patient cases and serves as an effective educational tool to gain knowledge and experience "without borders.", (© 2017 Wiley Periodicals, Inc.)

Objective/background: Children with Down syndrome (DS) have a high rate of pulmonary hypertension and sleepiness. They also have a high prevalence of obstructive sleep apnea syndrome (OSAS). We hypothesized that OSAS was associated with cardiovascular dysfunction and sleepiness in children with DS, and that this dysfunction was partly reversible., Patients/methods: A total of 23 children with DS, aged 8-19 years, were evaluated with polysomnography, echocardiography, and measurement of brain natriuretic peptide (BNP). Children having OSAS were randomized to four months of actual or sham continuous positive airway pressure (CPAP) in a double-blinded fashion., Results: Of the total participants, 20 (87%) had OSAS. On echocardiography, no participant was found to have pulmonary hypertension, and all participants had a BNP <10 pg/mL. The early/tissue Doppler (E/e') of the lateral mitral annulus, a measure of worse left ventricular (LV) diastolic function, correlated with the arousal index (r = 0.42, p = 0.043) and apnea hypopnea index (AHI; r = 0.61, p = 0.002) and inversely with the SpO2 nadir (r = -0.61, p = 0.002). Participants with OSAS had a high pediatric Epworth score [median interquartile range (IQR) = 8(4,9)],correlating with the arousal index (r = 0.49, p = 0.016). At four months, there were no changes in cardiovascular outcomes or sleepiness between those on actual versus sham CPAP. Hours of actual CPAP use was associated with improved E/e' mitral lateral (r = -0.48, p = 0.044), but surprisingly also correlated with LV mass z-score (r = 0.54, p = 0.018)., Conclusions: In children with DS, LV diastolic function correlated with OSAS severity, with improvement with CPAP use. There was a tendency towards increased sleepiness in those with OSAS, which correlated with the arousal index. Larger studies are warranted to confirm these findings., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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., (© 2015 by the American Heart Association, Inc., and the American Thoracic Society.)

Background: Cardiac catheterization is the standard of care procedure for diagnosis, choice of therapy, and longitudinal follow-up of children and adults with pulmonary hypertension (PH). However, the procedure is invasive and has risks associated with both the procedure and recovery period., Objectives: The purpose of this study was to identify risk factors for catastrophic adverse outcomes in children with PH undergoing cardiac catheterization., Methods: We studied children and young adults up to 21 years of age with PH undergoing 1 or more cardiac catheterization at centers participating in the Pediatric Health Information Systems database between 2007 and 2012. Using mixed-effects multivariable regression, we assessed the association between pre-specified subject- and procedure-level covariates and the risk of the composite outcome of death or initiation of mechanical circulatory support within 1 day of cardiac catheterization after adjustment for patient- and procedure-level factors., Results: A total of 6,339 procedures performed on 4,401 patients with a diagnosis of PH from 38 of 43 centers contributing data to the Pediatric Health Information Systems database were included. The observed risk of composite outcome was 3.5%. In multivariate modeling, the adjusted risk of the composite outcome was 3.3%. Younger age at catheterization, cardiac operation in the same admission as the catheterization, pre-procedural systemic vasodilator infusion, and hemodialysis were independently associated with an increased risk of adverse outcomes. Pre-procedural use of pulmonary vasodilators was associated with reduced risk of composite outcome., Conclusions: The risk of cardiac catheterization in children and young adults with PH is high relative to previously reported risk in other pediatric populations. The risk is influenced by patient-level factors. Further research is necessary to determine whether knowledge of these factors can be translated into practices that improve outcomes for children with PH., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Rationale: Infants with congenital diaphragmatic hernia (CDH) can develop pulmonary hypertension (PH) from decreased number and abnormal muscularization of pulmonary arteries. Normally pulmonary vascular growth and remodeling parallel airspace growth and alveolarization, which exhibits a wide morphologic variation in CDH., Aim: To assess whether infants with CDH and PH have greater abnormalities in infant pulmonary function testing (IPFT) compared to those without PH., Methods: We reviewed results of IPFTs and echocardiograms performed on infants with CDH from 2004 to June 2011. Lung volumes, forced flows and tidal mechanics were standardized according to available reference values. Comparisons between infants with and without PH were performed using linear regression, adjusting for potential confounders., Main Results: Sixty-six infants were included; 18 had PH and 48 did not. Z-score values for functional residual capacity (FRC), residual volume (RV), FRC/total lung capacity (TLC), and RV/TLC were significantly higher in infants with CDH and PH compared to those without PH. Z-score values for forced flows including forced expiratory volume in the first 0.5 sec (FEV0.5) and FEV0.5/forced vital capacity were significantly lower in infants with CDH and PH compared to those without PH. For 29 infants studied on ≥2 occasions, the slopes of FRC, RV, and TLC versus length were significantly higher in those with persistent PH compared to those without., Conclusions: Infants with CDH and persistent PH demonstrate greater airspace overdistension with growth compared to those without. Therapies that modify disrupted pulmonary vascular and alveolar formation could potentially improve future care of these patients., (© 2014 Wiley Periodicals, Inc.)

There are few data on the epidemiology of pulmonary hypertension (PH)-related hospitalizations in children in the United States. Our aim was to determine hospital mortality, length of hospitalization, and hospital charges pertaining to PH-related hospitalizations and also the effects of codiagnoses and comorbidities. A retrospective review of the Kids' Inpatient Database during the years 2000, 2003, 2006, and 2009 was analyzed for patients ≤20 years of age with a diagnosis of PH by ICD-9 (International Classification of Diseases, Ninth Revision) codes, along with associated diagnoses and comorbidities. Descriptive statistics, including Rao-Scott χ(2), ANOVA, and logistic regression models, were utilized on weighted values with survey analysis procedures. The number of PH-related hospital admissions is rising, from an estimated 7,331 (95% confidence interval [CI]: 5,556-9,106) in 2000 to 10,792 (95% CI: 8,568-13,016) in 2009. While infant age and congenital heart disease were most commonly associated with PH-related hospitalizations, they were not associated with mortality. Overall mortality for PH-related hospitalizations was greater than that for hospitalizations not associated with PH, 5.7% versus 0.4% (odds ratio: 16.22 [95% CI: 14.78%-17.8%], P < 0.001), but mortality is decreasing over time. Sepsis, respiratory failure, acute renal failure, hepatic insufficiency, arrhythmias, and the use of extracorporeal membrane oxygenation are associated with mortality. The number of PH-related hospitalizations is increasing in the United States. The demographics of PH in this study are evolving. Despite the increasing prevalence, mortality is improving.

Purpose: B-type natriuretic peptide (BNP), an established biomarker of ventricular pressure overload, is used in the assessment of children with pulmonary hypertension (PH). PH is commonly observed in congenital diaphragmatic hernia (CDH). However, the use of BNP levels to guide treatment in this patient population has not been well defined. In this study, we investigate BNP levels in a large cohort of CDH patients treated at a single institution., Methods: We retrospectively reviewed charts of all CDH patients enrolled in our pulmonary hypoplasia program from 2004-2013. PH was assessed by echocardiography using defined criteria, and patients were further stratified into the following cohorts: no PH, short-term PH (requiring nitric oxide but no additional vasodilatory therapy), long-term PH (requiring continued vasodilatory therapy post-discharge), and ECMO (requiring ECMO therapy)., Results: A total of 132 patients were studied. BNP levels were significantly increased in patients with PH compared to patients with normal pulmonary pressures (P<0.01). BNP levels were not significantly different between the ST-PH, LT-PH, and ECMO cohorts, but all levels in all three cohorts were significantly increased compared to patients who did not develop PH., Conclusion: Our findings indicate that plasma BNP levels correlate with pulmonary hypertension as well as the requirement for ECMO in CDH patients. Monitoring of serial BNP levels may provide a useful prognostic tool in the management of CDH., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Pulmonary hypoplasia has been described in cases of giant omphalocele (GO), although pulmonary hypertension (PH) has not been extensively studied in this disorder. In the present study, we describe rates and severity of PH in GO survivors who underwent standardized prenatal and postnatal care at our institution., Methods: A retrospective chart review was performed for all patients in our pulmonary hypoplasia program with a diagnosis of GO. Statistical significance was calculated using Fisher's exact test and Mann-Whitney test (p<0.05)., Results: Fifty-four patients with GO were studied, with PH diagnosed in twenty (37%). No significant differences in gender, gestational ages, birth weight, or Apgar scores were associated with PH. Patients diagnosed with PH were managed with interventions, including high frequency oscillatory ventilation, and nitric oxide. Nine patients required long-term pulmonary vasodilator therapy. PH was associated with increased length of hospital stay (p<0.001), duration of mechanical ventilation (p=0.008), and requirement for tracheostomy (p=0.0032). Overall survival was high (94%), with significantly increased mortality in GO patients with PH (p=0.0460). Prenatal imaging demonstrating herniation of the stomach into the defect was significantly associated with PH (p=0.0322), with a positive predictive value of 52%., Conclusions: In this series, PH was observed in 37% of GO patients. PH represents a significant complication of GO, and management of pulmonary dysfunction is a critical consideration in improving clinical outcomes in these patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Electrocardiograms have utility in disease stratification and monitoring in adult pulmonary arterial hypertension (PAH). We examined the electrocardiographic findings that are common in pediatric PAH and assessed for correlation with disease severity and progression. We retrospectively identified patients aged≤18 years followed at a single institution from January 2001 to June 2012 with catheterization-confirmed diagnosis of idiopathic PAH and PAH secondary to pulmonary developmental abnormalities. Patients with an electrocardiography performed within 60 days of catheterization were included. Primary and secondary outcomes are the prevalence of abnormal electrocardiographic findings at the time of catheterization and the association between electrocardiographic and hemodynamic findings and electrocardiographic changes with disease progression on follow-up catheterization, respectively. Of the 100 electrocardiography-catheterization pairs derived from the 46 patients identified, 93% had an electrocardiographic abnormality: 78% had right ventricular hypertrophy (RVH) and 52% had right axis deviation (RAD) for age. In patients with idiopathic PAH, the presence of RVH and RAD correlated with pulmonary vascular resistance and transpulmonary gradient. RAD and RVH on baseline electrocardiogram was associated with an increased risk of disease progression on subsequent catheterization (odds ratio 11.0, 95% confidence interval 1.3 to 96.2, p=0.03) after adjusting for PAH subgroup. The sensitivity, specificity, and positive and negative predictive values of RAD and RVH on baseline electrocardiogram for disease progression were 92%, 48%, 33%, and 95%, respectively. In conclusion, electrocardiographic abnormalities are common in pediatric PAH. RAD and RVH on electrocardiogram were associated with worse hemodynamics, whereas their absence is suggestive of a lack of disease progression., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Radiation exposure from pediatric cardiac catheterization may be substantial, although published estimates vary. We sought to report patient radiation dose across a range of diagnostic and interventional cases in a modern, high-volume pediatric catheterization laboratory. We retrospectively reviewed diagnostic and interventional cases performed in our pediatric catheterization laboratory from 1 April 2009 to 30 September 2011 for which radiation usage data were available as reported by the Artis Zee(®) (Siemens Medical Solutions) system. Electrophysiology cases were excluded. Radiation dose was quantified as air kerma dose (mGy) and dose-area product (DAP; μGy m(2)). The DAP was converted to an effective dose millisievert (mSv) using the Monte Carlo method. Radiation usage data were available from 2,265 diagnostic and interventional cases with an overall median air kerma dose of 135 mGy [interquartile range (IQR) 59-433], median DAP of 760 μGy m(2) (IQR 281-2,810), of which 75 % (IQR 59-90 %) was derived from fluoroscopy, and median effective dose of 6.2 mSv (IQR 2.7-14.1). Air kerma dose from a single camera >2,000 mGy occurred in 1.8 % of cases. Significant differences in all measures of radiation exposure existed based on procedural and interventional types (p = 0.0001), with interventional cases associated with the highest effective dose after adjusting for patient weight category (p < 0.001). Patient weight, age, fluoroscopy time, and proportional use of digital acquisition were independent predictors of exposure (p ≤ 0.001; R (2) = 0.59-0.64). In a modern, large-volume pediatric catheterization laboratory, the median effective dose is 6.2 mSv with a wide range of exposure based on patient- and procedure-specific factors. Radiation monitoring is an important component of a pediatric laboratory and further dose reduction strategies are warranted.

Rationale and Objectives: Cerebral oxygen extraction, defined as the difference between arterial and venous oxygen saturations (SaO2 and SvO2), is a critical parameter for managing intensive care patients at risk for neurological collapse. Although quantification of SaO2 is easily performed with pulse oximetry or moderately invasive arterial blood draws in peripheral vessels, cerebral SvO2 is frequently not monitored because of the invasiveness and risk associated with obtaining jugular bulb or super vena cava (SVC) blood samples., Materials and Methods: In this study, near-infrared spectroscopy (NIRS) was used to noninvasively measure cerebral SvO2 in anesthetized and mechanically ventilated pediatric patients (n = 10). To quantify SvO2, the NIRS signal component that fluctuates at the respiration frequency is isolated. This respiratory component is dominated by the venous portion of the interrogated vasculature. The NIRS measurements of SvO2 were validated against the clinical gold standard: invasively measured oxygen saturations from SVC blood samples. This technique was also applied in healthy volunteers (n = 5) without mechanical ventilation to illustrate its potential for use in healthy populations with natural airways., Results: Ten pediatric patients with pulmonary hypertension were studied. In these patients, SvO2 in the SVC exhibited good agreement with NIRS-measured SvO2 (R(2) = 0.80, P = .001, slope = 1.16 ± 0.48). Furthermore, in the healthy adult volunteers, mean (standard deviation) NIRS-measured SvO2 was 79.4 (6.8)%. This value is in good agreement with the expected average central venous saturation reported in literature., Conclusion: Respiration frequency-selected NIRS can noninvasively quantify cerebral SvO2. This bedside technique can be used to help assess brain health in neurologically unstable patients., (Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.)

There is a paucity of data on infant intravenous prostacyclin use, the gold standard for therapy for severe pulmonary hypertension (PH). This review aimed to evaluate the safety, tolerability, and outcomes of infant prostacyclin use. A retrospective observational study was performed in a large pediatric hospital with a dedicated pediatric PH program. Subject medical records, bedside flow sheets, and progress notes were reviewed to identify use of intravenous epoprostenol or treprostinil within the first year of life. The indication for prostacyclin use was recalcitrant hemodynamic compromise associated with PH, identified as either idiopathic PH, persistent PH of the newborn, PH associated with congenital diaphragmatic hernia, congenital heart disease, bronchiolitis, or chronic lung disease. Prostacyclin-related adverse events included 7 episodes of hypotension, 6 episodes of perceived pain, 2 episodes of cyanosis, and 1 episode of feeding intolerance. Prostacyclin was stopped only for cyanotic episodes associated with use in severe chronic lung disease. Two hemorrhagic events occurred during extracorporeal membrane oxygenation, which were unlikely to be prostacyclin related. Outcomes included 21 deaths unrelated to prostacyclin, 1 lung transplant, 6 PH resolutions, 8 transitions to oral PH medications, and 1 continuation of treprostinil. In conclusion, efficacy could not be evaluated in this study because of the loss of equipoise for neonatal prostacyclin use. Prostacyclin use was well tolerated in neonatal diseases associated with PH, but dose titration was limited by hypotension and hypoxemia.

Aim: Force due to leaning during cardiopulmonary resuscitation (CPR) negatively affects haemodynamics and intrathoracic airway pressures (ITP) in animal models and adults, but has not been studied in children. We sought to characterize the effects of sternal force (SF) comparable to leaning force on haemodynamics and ITP in anaesthetized children., Methods: Children (6 months to 8yrs) presenting for routine haemodynamic cardiac catheterization with anaesthesia and mechanical ventilation >6 months after cardiac transplant were studied. Haemodynamics and ITP were measured before and during incremental increases in SF of 10% and 20% body weight., Results: 20 subjects (5.4±1.7yrs of age and 18.3±3.3kg) were studied. Mean right atrial pressure (6.5±2.6 at baseline vs. 7.7±2.6 at 10% SF vs. 8.6±2.7mmHg at 20% SF), mean pulmonary capillary wedge pressure (10.2±2.9 at baseline vs. 11±3.3 at 10% SF vs. 11.8±3.4mmHg at 20% SF) and ITP (16.3±3.2 at baseline vs. 17.9±3.9 at 10% SF vs. 19.5±4cm H2O) all increased significantly with incremental SF (p<0.001 for all). Aortic systolic pressure (85±10mmHg at baseline vs. 83±10mmHg at 10% SF vs. 82±10mmHg at 20% SF, p=0.014) and coronary perfusion pressure (42±7mmHg at baseline vs. 39±7mmHg at 10% SF vs. 38±7mmHg at 20% SF, p<0.001) both decreased significantly with incremental SF., Conclusions: In asymptomatic, anaesthetized children after cardiac transplantation, sternal forces comparable to leaning previously reported to occur during CPR elevate ITP and right atrial pressure and decrease coronary perfusion pressure. These haemodynamic effects may be clinically important during CPR and warrant further study., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To describe the prevalence of and identify risk factors for acute occlusive arterial injury (AOAI) in a large volume pediatric cardiac catheterization laboratory., Background: AOAI is a known complication after pediatric cardiac catheterization. Prevalence and risk factors in the modern era are incompletely described., Methods: A retrospective cohort study including all cardiac catheterization procedures performed between January 1, 2005 and June 30, 2010 was performed. Case status was defined by ≥1 of the following: exam consistent with occlusive arterial injury, use of an anticoagulant within 48 hr of catheterization to restore or maintain patency of the artery, or documented occlusive arterial injury by radiologic study., Results: 3,254 patients had 5,715 catheterization procedures, which included 3,859 arterial access events. 167 cases of AOAI were identified for an overall prevalence of 4.3% among arterial access events. Multiple logistic regression identified independent risk factors: weight category [<4 kg: odds ratio (OR) 4.5 (95% CI: 2.6-7.7), P < 0.001; 4-6 kg: OR 2.1 (1.3-3.5), P = 0.002, compared to 6-8 kg referent group]; largest catheter outer diameter French size [OR 1.6 (1.3-1.9), P < 0.001]; final activated clotting time (ACT) <250 sec [OR 1.9 (1.4-2.7), P < 0.001]; and need for arterial catheter exchange [OR 1.8 (1.02-3.2), P = 0.04]., Conclusions: AOAI occurred in 4.3% of pediatric cardiac catheterizations, and was most likely in smaller children and those with larger arterial catheters. Risk was also independently increased by arterial catheter exchange and having a final ACT <250 sec. These data act as an important benchmark and identify areas for intervention for future studies., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: The significance and optimal treatment of systemic-to-pulmonary arterial collateral (SPC) vessels in single ventricle patients are poorly understood. The acute efficacy of SPC embolization has not been demonstrated in a quantifiable fashion. We sought to assess the acute efficacy of SPC embolization on blood flow as quantified by phase contrast magnetic resonance imaging and hypothesized that embolization acutely decreases SPC flow and increases systemic blood flow (Q(S))., Methods and Results: Six superior cavopulmonary connection patients underwent SPC flow quantification by phase contrast magnetic resonance imaging, including quantification of superior and inferior caval, total pulmonary artery, total pulmonary vein, ascending and descending aortic flows (Q(SVC), Q(IVC), Q(PA), Q(PV), Q(Ao), and Q(Dao), respectively), both immediately before and after cardiac catheterization with coil and particle embolization of angiographically evident SPC vessels. All studies were performed under a single anesthetic. After embolization, we found a significant decrease in SPC flow of 0.9 (range, 0.6-1.3) L/(min·m(2)) (P=0.03); a median reduction of 47% (range, 32-60). There was a significant decrease in the median Q(P):Q(S) from 1.3 before to 0.8 after embolization (P=0.03), and an increase in Q(S) from a median of 3.4 to 4.4 L/(min·m(2)) (P<0.05), and Q(SVC) from a median of 1.7 to 2.3 L/(min·m(2)) (P=0.03)., Conclusions: We report on the acute efficacy of SPC embolization, demonstrating a significant decrease in SPC flow and Q(P):Q(S) and increase in Q(SVC) and Q(S). Further studies are needed to assess the durability of the procedure and the effect on Fontan and longer-term outcomes.

The objective of this study was describe the impact of sildenafil on echocardiographic measures of myocardial performance in children and young adults with a functional single-ventricle physiology late after Fontan surgery. A double-blind, placebo-controlled, crossover trial was conducted in children and young adults after the Fontan operation at a single pediatric center. Subjects were randomized to receive placebo or sildenafil (20 mg tid) for 6 weeks. After a 6-week washout period, subjects were crossed for an additional 6 weeks. Each subject underwent an echocardiogram at the start and finish of each phase. A total of 27 subjects completed study testing at a mean age of 14.9 years and a mean time from Fontan surgery of 11.3 years. After sildenafil, subjects demonstrated improvement in their myocardial performance index (MPI; -0.051; 95% CI -0.095, -0.0077; p 0.02) and in the product of the velocity time integral (VTI) of the dominant outflow tract and the heart rate (HR; 110 cm × bpm; 95% CI 7.5, 220; p = 0.04). Measures of diastolic performance, including inflow velocities, myocardial velocities, and the ratio of blood pool velocity to myocardial velocity during passive inflow, did not change. In this cohort, there were significant improvements in both the MPI and the product of the VTI × HR after 6 weeks of treatment with sildenafil. These findings suggest that sildenafil may be a useful therapy to improve or maintain ventricular performance in select patients after the Fontan operation.

Background: Troponin I is often obtained during the evaluation of a potential transplant donor heart. It is not clear whether elevations in donor troponin I levels predict adverse outcomes and should thus preclude acceptance of a donor heart. This study examined whether troponin I levels from donors accepted for pediatric heart transplantation predicted graft failure., Methods: Deidentified data on heart transplants performed in recipients aged < 21 years between April 2007 and April 2009 was provided by the Organ Procurement and Transplantation Network. Donor troponin I level and recipient outcomes, including survival without retransplantation (graft survival), were examined for statistical correlation., Results: Overall graft survival in 839 heart transplants was 81% at 2 years. At least 1 troponin I level was recorded in 657 donors before transplant, with a median value of 0.1 ng/ml (range, 0-50 ng/ml). Troponin I level and graft status were not correlated (p = 0.74). A receiver operating characteristic curve showed no association between troponin I and graft status (area under the curve, 0.51; p = 0.98). Graft survival did not differ significantly (p = 0.60) among quartiles of troponin I levels (<0.04, 0.04-<0.1, 0.1-<0.35, ≥ 0.35 ng/ml). A troponin I level ≥ 1 ng/ml was found in 74 transplanted donor hearts; graft survival was not associated with troponin I ≥ 1 (80%) vs < 1 (80%) at 2 years (p = 0.93). Troponin I values were not associated with post-transplant hospital length of stay (r = -0.06; p = 0.10)., Conclusions: In donor hearts accepted for pediatric heart transplantation, troponin I elevation before procurement is not associated with increased graft failure. The significance of elevated troponin I levels, which occurs in many heart donors, remains unclear and should therefore be considered in the context of other clinical information., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Previous studies have demonstrated a correlation between E:E(a) and ventricular filling pressure in adults after heart transplantation. We sought to determine if E:E(a) correlates with filling pressure after heart transplantation in children. A prospective analysis of children who have undergone heart transplantation was performed. Inflow and myocardial velocities were recorded and compared to catheter-derived filling pressures and rejection status. We performed 61 studies in 49 subjects. No correlation was found between septal E:E(a) and PCWP (r=0.14, p=0.28); or between lateral tricuspid E:E(a) and mean RAp (r=0.04, p=0.79). However, the mean PCWP was higher among subjects with elevated septal E:E(a) (>12) compared to normal E:E(a) (12.3±2.8mmHg vs. 10.1±2.9mmHg, p=0.02). Similarly, mean RAp was higher among subjects with an elevated lateral tricuspid E:E(a) (>10) compared to normal lateral tricuspid E:E(a) (7.7±2.1mmHg vs. 6.0±2.4mmHg, p=0.04). Elevated septal E:E(a) was also associated with high-grade cellular rejection (OR=17.3 [95% CI 1.4-221], p=0.028). In children following heart transplant, E:E(a) does not correlate well with the range of filling pressures seen after pediatric heart transplantation. However, a septal E:E(a)>12 is associated with elevated PCWP and high grade cellular rejection and a lateral tricuspid E:E(a)>10 is associated with elevated mean RAp., (© 2011 John Wiley & Sons A/S.)

Introduction: Ellis - van Creveld syndrome is an autosomal recessive disorder manifest by short-limb dwarfism, thoracic dystrophy, postaxial polydactyly, dysplastic nails and teeth, and an approximately 60% incidence of congenital malformations of the heart. Despite patients with Ellis - van Creveld syndrome being regarded as having a high surgical risk, few data are available regarding their outcomes following surgery for congenital malformations of the heart in the current era., Materials and Methods: In this retrospective report, we summarise the clinical observations and outcomes of nine infants with Ellis - van Creveld syndrome who underwent surgery for congenital malformations of the heart between 2004 and 2009., Results: We identified 15 patients with Ellis - van Creveld syndrome during the study period; 11 (73%) had haemodynamically significant congenital malformations of the heart warranting surgery. In two of these patients, surgery was not performed. Of the nine patients who underwent surgery, all of whom were infants, eight (89%) had various forms of an atrioventricular septal defect and one patient (11%) had hypoplastic left heart syndrome (mitral and aortic atresia). Among the nine patients who underwent surgery, four (44%) died at a median of 102 days with a range of 25-149 days post-operatively, mostly from respiratory failure. Respiratory morbidity was seen in all surviving patients, of whom three underwent tracheostomy., Conclusions: Surgery for congenital malformations of the heart can be successful in infants with Ellis - van Creveld syndrome, but mortality is high and post-operative respiratory morbidity should be expected.

Background: Children and young adults with single-ventricle physiology have abnormal exercise capacity after the Fontan operation. A medication capable of decreasing pulmonary vascular resistance should allow improved cardiac filling and improved exercise capacity., Methods and Results: This study was a double-blind, placebo-controlled, crossover trial conducted in children and young adults after Fontan. Subjects were randomized to receive placebo or sildenafil (20 mg three times daily) for 6 weeks. After a 6-week washout, subjects crossed over for an additional 6 weeks. Each subject underwent an exercise stress test at the start and finish of each phase. After taking sildenafil, subjects had a significantly decreased respiratory rate and decreased minute ventilation at peak exercise. At the anaerobic threshold, subjects had significantly decreased ventilatory equivalents of carbon dioxide. There was no change in oxygen consumption during peak exercise, although there was a suggestion of improved oxygen consumption at the anaerobic threshold. Improvement at the anaerobic threshold was limited to the subgroup with single left or mixed ventricular morphology and to the subgroup with baseline serum brain natriuretic peptide levels ≥100 pg/mL., Conclusions: In this cohort, sildenafil significantly improved ventilatory efficiency during peak and submaximal exercise. There was also a suggestion of improved oxygen consumption at the anaerobic threshold in 2 subgroups. These findings suggest that sildenafil may be an important agent for improving exercise performance in children and young adults with single-ventricle physiology after the Fontan operation. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00507819.

Serum brain-type natriuretic peptide level (BNP) correlates with hemodynamic parameters measured during cardiac catheterization in adult patients with heart failure. We sought to describe the relationship of BNP with invasive hemodynamic measurements and cellular rejection in children following OHT. Children undergoing catheterization for OHT surveillance had simultaneous measurement of BNP. A total of 62 subjects were studied. The median BNP was 171 pg/mL (range 19-1130). There were significant positive correlations between BNP and mean PAP (R=0.33, p=0.009), RVSP (R=0.25, p=0.05), RVEDP (R=0.29, p=0.02), and mean RAP (R=0.39, p=0.002). Rejection grade varied from 0 to 3A (58 patients < ISHLT 3A and four patients ≥ ISHLT 3A). There was no significant difference in BNP based on cellular rejection grade. In a cohort of pediatric patients after heart transplantation, BNP correlates with direct measurements of right-sided pressures, but not with other hemodynamic measurements, time from transplant or rejection grade. This suggests that BNP may have a complimentary role in the monitoring of children following heart transplantation., (© 2010 John Wiley & Sons A/S.)

Objectives: This study sought to retrospectively evaluate our initial experience using angiographic computed tomography (ACT) in a pediatric cardiac catheterization laboratory., Background: ACT provides cross-sectional CT images from a rotational angiography run using a C-arm mounted flat-panel detector in the interventional suite. A 3-dimensional (3D) angiographic image can be created from the CT volume set and used in real time during the procedure. To our knowledge, its use has never previously been described for congenital heart disease., Methods: 3D reconstructions were created and we retrospectively reviewed cases during our first year of ACT use. Images obtained were independently evaluated to determine their diagnostic utility. Radiation dose reduction protocols were defined using phantom testing and radiation dose calculation., Results: ACT was used during 41 cardiac catheterizations in patients at a median age of 5.1 years (range: 0.4 to 58.8 years) for evaluation of: right ventricular outflow tract (RVOT)/central pulmonary arteries (PAs) in 20; cavopulmonary connection (CPC) in 11; pulmonary veins in 5; distal PAs in 4; and other locations in 5. Four subjects had 2 anatomic areas studied by ACT. The mean contrast volume for ACT was 1.2 ± 0.4 ml/kg. Diagnostic-quality imaging was obtained in 71% of cases: 13/20 RVOT/central PAs; 9/11 CPC; 4/5 pulmonary veins; 2/4 distal PAs; and 4/5 others. In 12 cases, ACT contributed to clinical outcomes beyond standard angiography. Radiation dose reduction protocols allowed ACT to be comparable in exposure to a standard biplane cineangiogram., Conclusions: Diagnostic-quality imaging can be obtained using ACT in 71% of cases without a significant increase in contrast or radiation exposure. In certain cases, ACT provides additional anatomic detail and may aid complex catheter manipulations. Future work is needed to continue to define applications of this new technology., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Ventricular assist devices (VAD) are associated with the formation of antibodies to anti-human leukocyte antigens (HLA) or sensitization. The incidence and effects of VAD-associated anti-HLA sensitization have not been well studied in the pediatric population., Methods: A retrospective review of all patients undergoing VAD implant at our institution from 1998 to 2008 was performed. Panel reactive antibody (PRA) results before VAD implant, after VAD implant, and after orthotopic heart transplantation (OHT) were recorded. Patients who became sensitized (PRA for class I and/or II immunoglobulin G antibodies >or= 10%) on VAD support were compared with non-sensitized patients with regard to demographics, diagnosis, device type, and blood product exposure on VAD support. Outcomes after OHT were also compared between groups., Results: VAD support was initiated in 20 patients (median age, 14.4 years), with 75% survival to OHT or recovery. PRA data before and after VAD implant were available for 17 patients. VAD-associated sensitization developed in 35% of recipients. There were no differences between those sensitized in association with VAD support and non-sensitized patients with regard to age, gender, diagnosis, device type, extracorporeal membrane oxygenation use, or blood product exposure on VAD support. Black race predicted sensitization on VAD (p = 0.02). There were no differences in survival or rejection between groups., Conclusions: VAD therapy was associated with the development of anti-HLA sensitization in 35% of recipients. Black race predicted sensitization, but there were no differences in overall survival or outcomes after OHT., (Copyright (c) 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Pathologies in both the respiratory and cardiovascular systems frequently coexist and impact on each other. This manuscript introduces an approach to the interpretation of this complex relationship. Pulmonary hypertension can be a significant consequence of many respiratory diseases. This in turn can lead to right ventricular dysfunction and cor pulmonale. Many childhood illnesses can result in cor pulmonale and can be conveniently grouped into three categories: idiopathic pulmonary hypertension, neonatal lung diseases, and lung disease beyond the neonatal period. When considering the impact of cardiac disease on the lung, one must consider two main pathologies: compression of the pediatric airway and increased lung water. In conclusion, thorough attention must be given to the interpretation of the complex relationship between cardiac and respiratory diseases. Pulmonary hypertension is a complication to consider in respiratory illness at all ages. In addition, when dealing with the complexities of congenital heart disease, one must always be aware of the risks of pulmonary complications whether parenchymal or airway. Ongoing improvements in ventilation strategies, vasodilator therapy, and surgical interventions continue to improve the outlook for these complex cases.

This case study reports the effects of a treprostinil accidental overdose in a patient with pulmonary hypertension. Treprostinil is labeled for treatment of pulmonary hypertension with New York Heart Association (NYHA) Class II, III and IV symptoms. It is characterized as a long-acting prostacyclin analog that can be delivered by intravenous or subcutaneous continuous infusions. This pediatric case report describes a massive overdose without significant side effects, thus suggesting a beneficial therapeutic index in pediatric patients.

Background: Body habitus assessment (BHA), be it wasted or obese, is a useful marker of nutritional status and overall medical condition. Wasting and obesity pre-heart transplant adversely affects outcomes in adults. The utility of BHA as a prognostic factor in children post-transplant is unknown., Methods: Weight and height at listing and standard growth charts were used to determine the ideal body weight (%IBW) and percentiles for body mass index for age (BMI%) and weight-for-length (W:L%). Wasting was defined as <90%IBW and/or 120%IBW and/or >or=95th percentile BMI% or W:L%. Outcomes of cohorts based on these criteria were compared., Results: From June 1990 to December 2006, 180 children, aged 5.81 +/- 6 years, were listed for transplant. Wasting occurred in 66 (37%) and obesity in 22 (12%) children, without differences between diagnoses of cardiomyopathy or congenital heart disease. %IBW was a prognostic factor for survival post-transplant on multivariate analysis: obese patients had a hazard ratio (HR) of 3.82 (95% confidence interval [CI] 1.81 to 8.06) compared with normal BHA (p < 0.001). Wasting had a survival advantage compared with normal BHA (HR 0.51, 95% CI 0.27 to 0.94, p = 0.032). There were no significant differences between cohorts in incidence of infections, first-year rejections or graft vasculopathy., Conclusions: Abnormal BHA at listing was a prognostic factor for survival post-transplant. Obese children had increased mortality, but wasting did not adversely affect post-transplant survival in our population. Body habitus assessment may risk-stratify children at listing, potentially providing a complex target for intervention.

Background: Risk factors for tricuspid regurgitation (TR) after adult orthotopic heart transplantation (OHT) have been reported, although there are no pediatric data., Methods: This study was a single-center retrospective analysis of patients

Background: No existing longitudinal data document exercise performance after pediatric heart transplantation. We report the exercise performance findings from the longitudinal study of pediatric heart transplantation patients and the association of aerobic capacity with echocardiographic measures of graft function., Methods: We performed a retrospective analysis of 28 children after heart transplantation who underwent 87 exercise tests and echocardiograms. Subjects exercised using graded cycle or treadmill protocols. Maximal oxygen consumption (VO2), physical working capacity, peak heart rate, and anaerobic threshold were evaluated. To measure systolic and diastolic function, shortening fraction and mitral valve pressure half-time (PHT) respectively, were obtained by echocardiography., Results: The average age at transplantation was 10.9 +/- 5.6 years, at initial exercise test was 13.8 +/- 5.0 years, and at final exercise test was 15.8 +/- 5.2 years. Percent-predicted values at the initial exercise test were VO2, 59.3%; physical working capacity, 60.2%; and peak heart rate, 75.8%; these remained similarly decreased at the final exercise test. Shortening fraction and PHT were within normal limits, but PHT was significantly greater at final test (p < 0.05). The relationship of VO2% with time was statistically significant, described by a quadratic equation that included initial VO2% and time from heart transplantation. This relationship remained significant when the shortening fraction (p < .05) but not PHT was added as a covariate in the equation., Conclusions: Exercise performance after pediatric heart transplantation is impaired and, despite an initial improvement, declines over time. This can be explained by increasing diastolic dysfunction independent of donor graft age. If confirmed, these findings point the direction to further research aimed at limiting this aerobic capacity decline after heart transplantation.

Background: Altered cardiac autonomic control may play a role in the morbidity and mortality suffered by neonates who undergo surgery for complex congenital heart disease (CHD). The purpose of this study was to evaluate cardiac autonomic activity, as measured by spectral indices of heart rate variability (HRV), prior to and early after infant surgery for CHD and attempt to correlate HRV indices with clinical outcome. In addition, we assessed the hypothesis that single-ventricle physiology and surgical interruption of the great arteries negatively affects HRV., Methods: Sixty neonates prospectively wore 24-hour Holter monitors at three time points: before and early after CHD surgery, and at 3- to 6-month follow-up. Standard spectral indices of HRV were measured., Results: In the early postoperative time point, patients with single-ventricle physiology had lower low-frequency power (LF) compared to patients with two ventricles (P=0.040). Surgical interruption of the great arteries did not affect HRV in this cohort. For the entire cohort, LF (P=0.004) and high-frequency power (HF) (P<0.001) increased over the three time points, while LF/HF (P=0.119) did not significantly change. In the multivariable linear regression model, significant predictors of longer postoperative hospital stay included longer total support time (P=or<0.001), longer duration of inotrope support (P=0.012), elevated mean heart rate at postoperative time point (P=0.002), and lower LF/HF ratio at the postoperative time point (P=0.014)., Conclusion: Patients with single-ventricle physiology have a significant physiologic reduction in LF in the early postoperative period compared to patients with two ventricles. Diminished cardiac autonomic control is associated with longer hospitalization following neonatal cardiac surgery.

Objective: To identify factors associated with mortality in children with heart disease managed with extracorporeal membrane oxygenation (ECMO)., Design: Retrospective chart review., Setting: Tertiary care university-affiliated children's hospital., Patients: All pediatric cardiac intensive care unit patients managed with ECMO between January 1, 1995, and June 30, 2001., Interventions: None., Results: During the study period, 137 patients were managed with ECMO in the pediatric cardiac intensive care unit. Of the 137 patients, 80 (58%) survived > or =24 hrs after decannulation, and 53 (39%) survived to hospital discharge. Patients managed with ECMO following cardiac surgery were analyzed separately from patients not in the postoperative period. Factors associated with an increased probability of mortality in the postoperative patients were age <1 month, male gender, longer duration of mechanical ventilation before ECMO, and development of renal or hepatic dysfunction while on ECMO. Single ventricle physiology and failure to separate from cardiopulmonary bypass were not associated with an increased risk of mortality. Cardiac physiology and indication for ECMO were not associated with mortality rate. Although longer duration of ECMO was not associated with increased mortality risk, patients with longer duration of ECMO were less likely to survive without heart transplantation., Conclusions: In a series of 137 patients managed with ECMO in a pediatric cardiac intensive care unit, survival to hospital discharge was 39%. In postoperative patients only, mortality risk was increased in males, patients <1 month old, patients with a longer duration of mechanical ventilation before initiation of ECMO, and patients who developed renal or hepatic failure while on ECMO.