Extracardiac Manifestations Fail to Predict the Severity of Cardiac Phenotype in Children and Young Adults with Marfan Syndrome.

We performed a secondary analysis of the Pediatric Heart Network (PHN) Marfan Trial public-use database to evaluate associations between extracardiac features and cardiac and aortic phenotypes in study participants. Aortic aneurysm phenotype was defined as aortic root Z-score ≥4.5, aortic root growth rate ≥75th percentile, aortic dissection, and aortic surgery. Severe cardiac phenotype was defined as aortic dissection, aortic Z-score ≥4.5, aortic valve surgery, at least moderate mitral regurgitation, mitral valve surgery, left ventricular dysfunction, or death. Extracardiac manifestations were characterized by specific organ system involvement and by a novel aggregate extracardiac score (AES) that was created for this study based on the original Ghent nosology. Mixed effects logistic regression analysis compared AES and systems involvement to outcomes. Of 608 participants (60% male), the median age at enrollment was 10.8 years (interquartile range: 6, 15.4). Aortic aneurysm phenotype was observed in 71% of participants and 64% had severe cardiac phenotype. On univariable analysis, skeletal (OR: 1.95, 95% CI: 1.01, 3.72; p = 0.05), skin manifestation (OR: 1.62, 95% CI: 1.13, 2.34; p = 0.01) and AES (OR: 1.17, 95% CI: 1.02, 1.34; p = 0.02) were associated with aortic aneurysm phenotype but were not significant in multivariable analysis. There was no association between extracardiac manifestations and severe cardiac phenotype. Thus, the severity of cardiac manifestations in Marfan syndrome (MFS) was independent of extracardiac phenotype and AES. Severity of extracardiac involvement did not appear to be a useful clinical marker for cardiovascular risk-stratification in this cohort of children and young adults with MFS.

Baseline Echocardiography and Laboratory Findings in MIS-C and Associations with Clinical Illness Severity.

Children with COVID-associated multisystem inflammatory syndrome (MIS-C) may develop severe disease. We explored the association of admission echocardiographic and laboratory parameters with MIS-C disease severity. This retrospective, single center study of consecutive MIS-C patients (4/2020-12/2021) excluded those with preexisting cardiomyopathy, congenital heart disease, or prior cardiotoxic therapy. Our hypothesis was that worse admission echocardiographic and laboratory parameters were associated with more severe disease based on vasoactive medication use. Univariable and multivariable logistic regression models assessed the association between vasoactive medication use and baseline variables. Of 118 MIS-C patients, median age was 7.8 years (IQR 4.6, 11.8), 48% received vasoactive medication. Higher admission brain natriuretic peptide [OR 1.07 (95% CI 1.02,1.14), p = 0.019], C-reactive protein [OR 1.08 (1.03,1.14), p = 0.002], troponin [OR 1.05 (1.02,1.1), p = 0.015]; lower left ventricular ejection fraction [LVEF, OR 0.96 (0.92,1), p = 0.042], and worse left atrial reservoir strain [OR 0.96 (0.92,1), p = 0.04] were associated with vasoactive medication use. Only higher CRP [OR 1.07 (1.01, 1.11), p = 0.034] and lower LVEF [0.91 (0.84,0.98), p = 0.015] remained independently significant. Among those with normal admission LVEF (78%, 92/118), 43% received vasoactive medication and only higher BNP [OR 1.09 (1.02,1.19), p = 0.021 per 100 pg/mL] and higher CRP [OR 1.07 (1.02,1.14), p = 0.013] were associated with use of vasoactive medication. Nearly half of all children admitted for MIS-C subsequently received vasoactive medication, including those admitted with a normal LVEF. Similarly, admission strain parameters were not discriminatory. Laboratory markers of systemic inflammation and cardiac injury may better predict early MIS-C disease severity.

Left Atrial Strain in Multisystem Inflammatory Syndrome in Children and Associations with Systemic Inflammation and Cardiac Injury.

Multisystem inflammatory syndrome in children (MIS-C) commonly involves cardiac injury with both systolic and diastolic dysfunction. Left atrial strain (LAS) detects subclinical diastolic dysfunction in adults but is infrequently used in children. We evaluated LAS in MIS-C and the associations with systemic inflammation and cardiac injury. In this retrospective cohort study, LAS parameters [reservoir (LAS-r), conduit (LAS-cd), and contractile (LAS-ct)] obtained from admission echocardiograms of MIS-C patients were compared to healthy controls and between MIS-C patients with and without cardiac injury (BNP > 500 pg/ml or troponin-I > 0.04 ng/ml). Correlation and logistic regression analyses were performed to assess LAS associations with admission inflammatory and cardiac biomarkers. Reliability testing was performed. We identified 118 patients with MIS-C and 20 healthy controls. Median LAS parameters were reduced in MIS-C patients compared to controls (LAS-r: 31.8 vs. 43.1%, p < 0.001; LAS-cd: - 28.8 vs. - 34.5%, p = 0.006; LAS-ct: - 5.2 vs. - 9.3%, p < 0.001) and reduced in MIS-C patients with cardiac injury (n = 59) compared to no injury (n = 59) (LAS-r: 29.6 vs. 35.8%, p = 0.001; LAS-cd: - 26.5 vs. - 30.4%, p = 0.036; LAS-ct: - 4.6 vs. - 9.3%, p = 0.008). A discrete LAS-ct peak was absent in 65 (55%) MIS-C patients but present in all controls (p < 0.001). Procalcitonin correlated strongly with averaged E/e' (r = 0.55, p = 0.001). Moderate correlations were found for ESR and LAS-ct (r = - 0.41, p = 0.007) as well as BNP and LAS-r (r = - 0.39, p < 0.001) and LAS-ct (r = 0.31, p = 0.023). Troponin-I had only weak correlations. Intra-rater reliability was good for all LAS parameters, and inter-rater reliability was good to excellent for LAS-r, and fair for LAS-cd and LAS-ct. LAS analysis, particularly the absence of a LAS-ct peak, was reproducible and may be superior to conventional echocardiographic parameters for detecting diastolic dysfunction in MIS-C. No strain parameters on admission were independently associated with cardiac injury.

Limited Relationship Between Echocardiographic Measures and Electrocardiographic Markers of Left Ventricular Size in Healthy Children.

Pediatric ECG standards have been defined without echocardiographic confirmation of normal anatomy. The Pediatric Heart Network Normal Echocardiogram Z-score Project provides a racially diverse group of healthy children with normal echocardiograms. We hypothesized that ECG and echocardiographic measures of left ventricular (LV) dimensions are sufficiently correlated in healthy children to imply a clinically meaningful relationship. This was a secondary analysis of a previously described cohort including 2170 digital ECGs. The relationship between 6 ECG measures associated with LV size were analyzed with LV Mass (LVMass-z) and left ventricular end-diastolic volume (LVEDV-z) along with 11 additional parameters. Pearson or Spearman correlations were calculated for the 78 ECG-echocardiographic pairs with regression analyses assessing the variance in ECG measures explained by variation in LV dimensions and demographic variables. ECG/echocardiographic measurement correlations were significant and concordant in 41/78 (53%), though many were significant and discordant (13/78). Of the 6 ECG parameters, 5 correlated in the clinically predicted direction for LV Mass-z and LVEDV-z. Even when statistically significant, correlations were weak (0.05-0.24). R2 was higher for demographic variables than for echocardiographic measures or body surface area in all pairs, but remained weak (R2 ≤ 0.17). In a large cohort of healthy children, there was a positive association between echocardiographic measures of LV size and ECG measures of LVH. These correlations were weak and dependent on factors other than echocardiographic or patient derived variables. Thus, our data support deemphasizing the use of solitary, traditional measurement-based ECG markers traditionally thought to be characteristic of LVH as standalone indications for further cardiac evaluation of LVH in children and adolescents.

Center-level factors associated with shorter length of stay following stage 1 palliation: An analysis of the national pediatric cardiology quality improvement collaborative registry.

BACKGROUND: Stage 1 single ventricle palliation (S1P) has the longest length of stay (LOS) of all benchmark congenital heart operations. Center-level factors contributing to prolonged hospitalization are poorly defined. METHODS: We analyzed data from infants status post S1P included in the National Pediatric Cardiology Quality Improvement Collaborative Phase II registry. Our primary outcome was patient-level LOS with days alive and out of hospital before stage 2 palliation (S2P) used as a balancing measure. We compared patient and center-level characteristics across quartiles for median center LOS, and used multivariable regression to calculate center-level factors associated with LOS after adjusting for case mix. RESULTS: Of 2,510 infants (65 sites), 2037 (47 sites) met study criteria (61% male, 61% white, 72% hypoplastic left heart syndrome). There was wide intercenter variation in LOS (first quartile centers: median 28 days [IQR 19, 46]; fourth quartile: 62 days [35, 95], P < .001). Mortality prior to S2P did not differ across quartiles. Shorter LOS correlated with more pre-S2P days alive and out of hospital, after accounting for readmissions (correlation coefficient -0.48, P < .001). In multivariable analysis, increased use of Norwood with a right ventricle to pulmonary artery conduit (aOR 2.65 [1.1, 6.37]), shorter bypass time (aOR 0.99 per minute [0.98,1.0]), fewer additional cardiac operations (aOR 0.46 [0.22, 0.93]), and increased use of NG tubes rather than G tubes (aOR 7.03 [1.95, 25.42]) were all associated with shorter LOS centers. CONCLUSIONS: Modifiable center-level practices may be targets to standardize practice and reduce overall LOS across centers.

Pediatric Heart Network Trial of Losartan vs. Atenolol in Children and Young Adults with Marfan Syndrome: Impact on Prescription Practices.

The Pediatric Heart Network (PHN) trial showed similar efficacy of ß-blockers (BB) and angiotensin receptor blockers (ARB) for aortic root dilation in Marfan syndrome, but the impact on prescription practices is unknown. We hypothesized BB and ARB prescriptions would increase after the trial results were published (2014). Prescription data (2007-2016) were obtained from outpatient encounters (IBM Marketscan) for Marfan syndrome patients (6 months-25 years old). Excluding 2014 as a washout period, we analyzed two intervals: 2007-2013 and 2015-2016. Medication categories included BB, ARB, angiotensin converting enzyme inhibitors (ACEI), combination (BB/ARB and/or BB/ACEI), and no drug. Interrupted time-series analysis assessed immediate level change after publication and change in slope for the trend pre- and post-publication. Odds ratios (OR) and 95% confidence intervals from logistic regressions and generalized estimating equation methods accounted for correlation of prescriptions within patients. In 1499 patients (age 14.1 ± 6.1 years, 59% female) seen 2007-2013, BB trended lower [OR 0.91 (0.89, 0.93), p < 0.001] and ARB trended higher [OR 1.12 (1.07, 1.18), p < 0.001], while combination, ACEI, and no drug remained stable. This trend persisted, but was not significant, for BB [OR 0.54 (0.27, 1.08), p = 0.37] and ARB [OR 1.91 (0.55, 6.69), p = 0.31] in 2015-2016. Combination, ACEI, and no drug remained similar. In short term follow-up, changes in prescription practices following publication of the PHN trial were not statistically significant. This may be due to a change seen prior to publication with early adoption of ARBs that was maintained after confirmation of their effectiveness.

Coronary artery dilation associated with bicuspid and unicuspid aortic valve disease in children: a series of 17 patients.

INTRODUCTION: Coronary artery dilation associated with bicuspid/unicuspid aortic valves is described in adults with limited data in children. We aimed to describe the clinical course of children with bicuspid/unicuspid aortic valves and coronary dilation including coronary Z-score changes over time, association of coronary changes with aortic valve anatomy/function, and complications. MATERIALS AND METHODS: Institutional databases were searched for children ≤18 years with both bicuspid/unicuspid aortic valves and coronary dilation (1/2006-6/2021). Kawasaki disease and isolated supra-/subvalvar aortic stenosis were excluded. Statistics were descriptive with associations measured by Fisher's exact test and overlapping 83.7% confidence intervals. RESULTS: Of 17 children, bicuspid/unicuspid aortic valve was diagnosed at birth in 14 (82%). Median age at coronary dilation diagnosis was 6.4 years (range: 0-17.0). Aortic stenosis was present in 14 (82%) [2 (14%) moderate, 8 (57%) severe]; 10 (59%) had aortic regurgitation; 8 (47%) had aortic dilation. The right coronary was dilated in 15 (88%), left main in 6 (35%), and left anterior descending in 1 (6%) with no relationship between leaflet fusion pattern or severity of aortic regurgitation/stenosis on coronary Z-score. Follow-up evaluations were available for 11 (mean 9.3 years, range 1.1-14.8) with coronary Z-scores increasing in 9/11 (82%). Aspirin was used in 10 (59%). There were no deaths or coronary artery thrombosis. DISCUSSION: In children with bicuspid/unicuspid aortic valves and coronary dilation, the right coronary artery was most frequently involved. Coronary dilation was observed in early childhood and frequently progressed. Antiplatelet medication use was inconsistent, but no child died nor developed thrombosis.

Variation in provider compliance with sports restriction guidelines in children with an isolated bicuspid aortic valve.

BACKGROUND: Published guidelines for sports restriction for children with a bicuspid aortic valve remain controversial. We sought to describe practice variation and factors influencing sports restrictions in these children. METHODS: This retrospective single-centre study included children (7-18 years old) with an isolated bicuspid aortic valve at baseline from 1 January, 2005 to 31 December, 2014. Sports restrictions, factors potentially influencing decision-making, and outcomes were collected. Descriptive statistics and multivariable mixed-effects logistic regression models were performed with providers and patients as random effects. Provider variation was estimated using intraclass correlation coefficients. Odds ratios, 95% confidence intervals, and p-values were reported from the models. RESULTS: In 565 encounters (253 children; 34 providers), 41% recommended no sports restrictions, 40% recommended high-static and high-dynamic restrictions, and 19% had no documented recommendations. Based on published guidelines, 22% of children were inappropriately restricted while 30% were not appropriately restricted. The paediatric cardiology provider contributed to 37% of observed practice variation (p < 0.001). Sports restriction was associated with older age, males, greater ascending aorta z-score, and shorter follow-up interval. There were no aortic dissections or deaths and one cardiac intervention. CONCLUSION: Physicians frequently fail to document sports restrictions for children with a bicuspid aortic valve, and documented recommendations often conflict with published guidelines. Despite this, no adverse outcomes occurred. Providers accounted for a significant proportion of the variation in sports restrictions. Further research to provide evidence-based guidelines may improve provider compliance with activity recommendations in this population.

The pediatric heart network's study on long-term outcomes of children with HLHS and the impact of Norwood Shunt type in the single ventricle reconstruction trial cohort (SVRIII): Design and adaptations.

BACKGROUND: The Single Ventricle Reconstruction (SVR) Trial was the first randomized clinical trial of a surgical approach for treatment of congenital heart disease. Infants with hypoplastic left heart syndrome (HLHS) and other single right ventricle (RV) anomalies were randomized to a modified Blalock Taussig Thomas shunt (mBTTS) or a right-ventricular-to-pulmonary-artery shunt (RVPAS) at the time of the Norwood procedure. The aim of the Long-term Outcomes of Children with HLHS and the Impact of Norwood Shunt Type (SVR III) study is to compare early adolescent outcomes including measures of cardiac function, transplant-free survival, and neurodevelopment, between those who received a mBTTS and those who received an RVPAS. METHODS: Transplant-free survivors of the SVR cohort were enrolled at 10 to 15 years of age for multifaceted in-person evaluation of cardiac function (cardiac magnetic resonance [CMR], echocardiogram and exercise test) and neurodevelopmental evaluation. Right ventricular ejection fraction measured by CMR served as the primary outcome. Development of arrhythmias, protein losing enteropathy, and other comorbidities were assessed through annual medical history interview. Through the course of SVR III, protocol modifications to engage SVR trial participants were designed to enhance recruitment and retention. CONCLUSIONS: Evaluation of long-term outcomes will provide important data to inform decisions about the shunt type placed at the Norwood operation and will improve the understanding of cardiovascular and neurodevelopmental outcomes for early adolescents with HLHS.

The impact of the American Heart Association guidelines on patients treated for incomplete Kawasaki disease.

OBJECTIVES: To compare patients treated for incomplete Kawasaki disease whose practitioners followed versus did not follow American Heart Association criteria and to evaluate the association of cardiology consultation with adherence to these guidelines. STUDY DESIGN: Single centre retrospective cohort study of patients <18 years old who received ≥1 dose of intravenous immunoglobulin for Kawasaki disease between 01/2006 and 01/2018. We collected demographics, clinical and laboratory data, coronary artery abnormalities, and cardiology consultation status. Patients treated for incomplete Kawasaki disease were divided into two groups based on adherence versus nonadherence to American Heart Association guidelines and compared by Wilcoxon rank sum test and chi-squared or Fisher's exact test. RESULTS: Of the 357 patients treated for Kawasaki disease, 109 (31%) were classified as incomplete Kawasaki disease. The American Heart Association algorithm for identifying patients with incomplete Kawasaki disease was followed in 81/109 (74%). Coronary artery abnormalities were present in 46/109 (42%) of the patients who were treated for incomplete Kawasaki disease. Cardiology consultation was more frequent in those fulfilling American Heart Association criteria for the diagnosis of incomplete Kawasaki disease versus those who did not fulfill criteria (76% versus 48%, p = 0.005). CONCLUSIONS: Over 25% of patients treated for incomplete Kawasaki disease did not meet American Heart Association guidelines. Guidelines were more frequently followed when the paediatric cardiology team was consulted. Consulting physicians with experience and expertise in the evaluation and management of incomplete KD should be strongly considered in the care of these patients.

Poor Weight Recovery Between Stage 1 Palliation and Hospital Discharge for Infants with Single Ventricle Physiology: An Analysis of the National Pediatric Cardiology Quality Improvement Collaborative Phase II Dataset.

OBJECTIVE: To investigate change in weight-for-age z-scores (WAZ) and risk factors for impaired weight gain between stage 1 palliation (S1P) for single ventricle physiology and discharge. STUDY DESIGN: This was a secondary analysis of the National Pediatric Cardiology Quality Improvement Collaborative Phase II database. The primary outcome was change in WAZ between S1P and discharge. Risk factors were selected using multivariable mixed effects regression constructed by step-wise model selection, with adjustment for WAZ at S1P and a random effect for center. RESULTS: Of 730 infants who were discharged after S1P, WAZ decreased in 98.6% (-1.5 ± 0.7). WAZ at discharge was <-1 but >-2 (at risk) in 40% and <-2 (failure to thrive) in 35% of participants. Males, higher WAZ at S1P, non-S1P procedures (mostly noncardiac), increased length of stay, necrotizing enterocolitis, and angiotensin-converting enzyme inhibitor use at discharge were associated with a greater decrease in WAZ. Preoperative enteral feeding and respiratory medications were associated with a lesser decrease in the WAZ. CONCLUSIONS: Nearly all infants lose weight after S1P with little recovery by hospital discharge. At discharge, three-quarters of the infants in the cohort were at risk for impaired weight gain or had failure to thrive. Most risk factors associated with change in WAZ were unmodifiable or surrogates of disease severity. Novel interventions are needed to minimize the early catabolic effects and promote anabolic recovery after S1P.

Implications of Left Ventricular Dysfunction at Presentation for Infants with Coarctation of the Aorta.

Infants with aortic coarctation may present with left ventricular (LV) dysfunction which may complicate the postoperative course and lead to increased healthcare costs. We aimed to define the prevalence of moderate to severe left ventricular (LV) systolic dysfunction, evaluate time to recovery, and compare health care costs. Single-center retrospective cohort study at a tertiary care hospital was conducted. Infants < 6 months old at diagnosis with aortic coarctation were identified using surgical codes for coarctation repair between January 2010 and May 2018. Moderate to severe dysfunction was defined as ejection fraction (EF) < 40%. Of 160 infants studied, 18 (11%) had moderate to severe LV dysfunction at presentation. Compared to those with better LV function, infants with moderate to severe LV dysfunction were older at presentation (12 vs. 6 days, p = 0.004), had more postoperative cardiac intensive care unit (ICU) days (5 vs. 3, p < 0.001), and more ventilator days (3.5 vs. 1, p < 0.001). The median time to normal LV EF (≥ 55%) was 6 days postoperatively (range 1-230 days). Infants presenting with moderate to severe LV dysfunction had higher index hospitalization costs ($90,560 vs. $59,968, p = 0.02), but no difference in cost of medical follow-up for the first year following discharge ($3,078 vs. $2,568, p = 0.46). In the current era, > 10% of infants with coarctation present with moderate to severe LV dysfunction that typically recovers. Those with moderate to severe dysfunction had longer duration of mechanical ventilation and postoperative cardiac ICU stays, likely driving higher costs of index hospitalization.

Implications of Changing Z-Score Models for Coronary Artery Dimensions in Kawasaki Disease.

BACKGROUND: Coronary artery abnormalities in Kawasaki disease (KD) are assessed using echocardiographic z-scores. We hypothesized that changing the coronary artery (CA) z-score model would alter diagnosis and management of children with KD. METHODS: In this retrospective single-center study of children treated for KD (9/2007-1/2020), we collected echocardiographic measurements for the left anterior descending (LAD), right (RCA), and left main (LMCA) coronary arteries during 3 illness phases and calculated Boston and Pediatric Heart Network (PHN) z-scores. Agreement between Boston and PHN z-scores was assessed using Kappa (κ) and Lin's Concordance Correlation Coefficients (CCC) and Bland-Altman analysis. RESULTS: For 904 echocardiograms from 357 children, the median Boston LAD z-score was lower than the PHN (0.3 [IQR - 0.6, 1.5] vs 1.6 [IQR 0.7, 2.8], CCC 0.94 [95% CI 0.93, 0.95], moderate agreement), aggregated across all illness phases. RCA and LMCA z-scores showed substantial agreement. With conversion from Boston to PHN models, the percentage of individual LAD z-scores ≥ 2.5 increased (14.6% to 32.1%). At least one CA z-score classification changed in 213 children (59.7%) across all phases, and 48 children (13.4%) had a change that altered recommended antithrombotic strategy. Agreement between models differed by age, sex, and race. CONCLUSIONS: Conversion from Boston to PHN z-scores changed at least 1 CA z-score classification in over half of KD patients and changed recommended antithrombotic management in 13%, largely driven by LAD measurements. Since diagnosis and management of KD and KD-like diseases rely upon CA z-scores, the clinical and research implications of these findings merit further exploration.

Changes in Provider Prescribing Behavior for Infants with Single Ventricle Physiology After Evidence-Based Publications.

BACKGROUND: The impact of published evidence on clinical practice has been understudied in pediatric cardiology. OBJECTIVE: We sought to assess changes in prescribing behavior for angiotensin-converting enzyme inhibitor (ACEI) and digoxin at discharge after initial palliation of infants with single ventricle (SV) physiology following the publication of two large studies: The Pediatric Heart Network Infant Single Ventricle (PHN-ISV) trial showing no benefit with routine ACEI use and the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) analysis showing an association between digoxin and survival. METHODS: ICD-9-10 codes identified SV infants from the Pediatric Health Information System (1/2004 to 1/2018) and charge codes identified medications at discharge. Generalized estimating equations implementing segmented logistic regressions modeled medication use, before and after (with a 3-month washout period) the relevant publication (ACEI 7/1/2010; digoxin 4/1/2016). A subgroup analysis was performed for hypoplastic left heart syndrome (HLHS). RESULTS: ACEI use (37 centers, n = 4700) at discharge did not change over time during the pre-publication period. After publication of the PHN-ISV trial, ACEI use decreased (OR: 0.61, CI 0.44-0.84, p = 0.003). Digoxin use (43 centers, n = 4778) decreased by 1% monthly before publication. After the NPC-QIC publication, digoxin use increased (OR: 2.07, CI 1.05-4.08, p = 0.04) with an ongoing increase of 9% per month. Results were similar for the HLHS subgroup. CONCLUSIONS: Prescribing behavior changed congruently after the publication of evidence-based studies, with decreased ACEI use and increased digoxin use at discharge following initial palliation of SV infants. Our findings suggest scientific findings were rapidly implemented into clinical practice.

Factors That Contribute to Cost Differences Based on ICU of Admission in Neonates Undergoing Congenital Heart Surgery: A Novel Decomposition Analysis.

OBJECTIVES: We leveraged decomposition analysis, commonly used in labor economics, to understand determinants of cost differences related to location of admission in children undergoing neonatal congenital heart surgery. DESIGN: A retrospective cohort study. SETTING: Pediatric Health Information Systems database. PATIENTS: Neonates (<30 d old) undergoing their index congenital heart surgery between 2004 and 2013. MEASUREMENTS AND MAIN RESULTS: A decomposition analysis with bootstrapping determined characteristic (explainable by differing covariate levels) and structural effects (if covariates are held constant) related to cost differences. Covariates included center volume, age at admission, prematurity, sex, race, genetic or major noncardiac abnormality, Risk Adjustment for Congenital Heart Surgery-1 score, payor, admission year, cardiac arrest, infection, and delayed sternal closure.Of 19,984 infants included (10,491 [52%] to cardiac ICU/PICU and 9,493 [48%] to neonatal ICU), admission to the neonatal ICU had overall higher average costs ($24,959 ± $3,260; p < 0.001) versus cardiac ICU/PICU admission. Characteristic effects accounted for higher costs in the neonatal ICU ($28,958 ± $2,044; p < 0.001). Differing levels of prematurity, genetic syndromes, hospital volume, age at admission, and infection contributed to higher neonatal ICU costs, with infection rate providing the most significant contribution ($13,581; p < 0.001). Aggregate structural effects were not associated with cost differences for those admitted to the neonatal ICU versus cardiac ICU/PICU (p = 0.1). Individually, prematurity and age at admission were associated with higher costs due to structural effects for infants admitted to the neonatal ICU versus cardiac ICU/PICU. CONCLUSIONS: The difference in cost between neonatal ICU and cardiac ICU/PICU admissions is largely driven by differing prevalence of risk factors between these units. Infection rate was a modifiable factor that accounted for the largest difference in costs between admitting units.

Physician Barriers and Facilitators for Screening for Congenital Heart Disease With Routine Obstetric Ultrasound: A National United States Survey.

OBJECTIVES: Prenatal detection of congenital heart disease with obstetric screening remains at less than 50% in most population studies, far from what is thought to be achievable. We sought to identify barriers/facilitators for screening from the perspective of interpreting physicians and to understand how these barriers/facilitators may be associated with interpretation of screening images. METHODS: Our mixed-methods studies included 4 focus groups in centers across the United States with obstetric, maternal-fetal medicine, and radiology providers who interpreted obstetric ultrasound studies. Themes around barriers/facilitators for fetal heart screening were coded from transcripts. A national Web-based survey was then conducted, which quantitatively measured reported barriers/facilitators and measured physicians' ability to interpret fetal heart-screening images. Multivariable generalized linear random-effect models assessed the association between barriers/facilitators and the accuracy of image interpretation at the image level. RESULTS: Three main themes were identified in the focus groups: intrinsic barriers (ie, comfort with screening), external barriers (ie, lack of feedback), and organizational barriers (ie, study volumes). Among 190 physician respondents, 104 interpreted ultrasound studies. Perceptions of barriers varied by practice setting, with nontertiary providers having lower self-efficacy and perceived usefulness of cardiac screening. Facilitators associated with the odds of accurate interpretation of screening images were knowledge (odds ratio, 2.54; P = .002) and the volume of scans per week (odds ratio, 1.01 for every additional scan; P = .04). CONCLUSIONS: Some of the main barriers to cardiac screening identified and prioritized by physicians across the United States were knowledge of screening and minimal volumes of scans. Targeting these barriers will aid in improving prenatal detection of congenital heart disease.

Challenges and lessons learned from the Pediatric Heart Network Normal Echocardiogram Database study.

BACKGROUND: The Pediatric Heart Network Normal Echocardiogram Database Study had unanticipated challenges. We sought to describe these challenges and lessons learned to improve the design of future studies. METHODS: Challenges were divided into three categories: enrolment, echocardiographic imaging, and protocol violations. Memoranda, Core Lab reports, and adjudication logs were reviewed. A centre-level questionnaire provided information regarding local processes for data collection. Descriptive statistics were used, and chi-square tests determined differences in imaging quality. RESULTS: For the 19 participating centres, challenges with enrolment included variations in Institutional Review Board definitions of "retrospective" eligibility, overestimation of non-White participants, centre categorisation of Hispanic participants that differed from National Institutes of Health definitions, and exclusion of potential participants due to missing demographic data. Institutional Review Board amendments resolved many of these challenges. There was an unanticipated burden imposed on centres due to high numbers of echocardiograms that were reviewed but failed to meet submission criteria. Additionally, image transfer software malfunctions delayed Core Lab image review and feedback. Between the early and late study periods, the proportion of unacceptable echocardiograms submitted to the Core Lab decreased (14 versus 7%, p < 0.01). Most protocol violations were from eligibility violations and inadvertent protected health information disclosure (overall 2.5%). Adjudication committee reviews led to protocol changes. CONCLUSIONS: Numerous challenges encountered during the Normal Echocardiogram Database Study prolonged study enrolment. The retrospective design and flaws in image transfer software were key impediments to study completion and should be considered when designing future studies collecting echocardiographic images as a primary outcome.

Variation in care for children undergoing the Fontan operation for hypoplastic left heart syndrome.

BACKGROUND: The Single Ventricle Reconstruction Trial randomised neonates with hypoplastic left heart syndrome to a shunt strategy but otherwise retained standard of care. We aimed to describe centre-level practice variation at Fontan completion. METHODS: Centre-level data are reported as median or median frequency across all centres and range of medians or frequencies across centres. Classification and regression tree analysis assessed the association of centre-level factors with length of stay and percentage of patients with prolonged pleural effusion (>7 days). RESULTS: The median Fontan age (14 centres, 320 patients) was 3.1 years (range from 1.7 to 3.9), and the weight-for-age z-score was -0.56 (-1.35 + 0.44). Extra-cardiac Fontans were performed in 79% (4-100%) of patients at the 13 centres performing this procedure; lateral tunnels were performed in 32% (3-100%) at the 11 centres performing it. Deep hypothermic circulatory arrest (nine centres) ranged from 6 to 100%. Major complications occurred in 17% (7-33%). The length of stay was 9.5 days (9-12); 15% (6-33%) had prolonged pleural effusion. Centres with fewer patients (<6%) with prolonged pleural effusion and fewer (<41%) complications had a shorter length of stay (<10 days; sensitivity 1.0; specificity 0.71; area under the curve 0.96). Avoiding deep hypothermic circulatory arrest and higher weight-for-age z-score were associated with a lower percentage of patients with prolonged effusions (<9.5%; sensitivity 1.0; specificity = 0.86; area under the curve 0.98). CONCLUSIONS: Fontan perioperative practices varied widely among study centres. Strategies to decrease the duration of pleural effusion and minimise complications may decrease the length of stay. Further research regarding deep hypothermic circulatory arrest is needed to understand its association with prolonged pleural effusion.

Early Childhood Inpatient Costs of Critical Congenital Heart Disease.

OBJECTIVE: To assess longitudinal estimates of inpatient costs through early childhood in patients with critical congenital heart defects (CCHDs), for whom reliable estimates are scarce, using a population-based cohort of clinically validated CCHD cases. STUDY DESIGN: Longitudinal retrospective cohort of infants with CCHDs live born from 1997 to 2012 in Utah. Cases identified from birth defect registry data were linked to inpatient discharge abstracts and vital records to track inpatient days and costs through age 10 years. Costs were adjusted for inflation and discounted by 3% per year to generate present value estimates. Multivariable models identified infant and maternal factors potentially associated with higher resource utilization and were used to calculate adjusted costs by defect type. RESULTS: The final statewide cohort included 1439 CCHD cases among 803 509 livebirths (1.8/1000). The average cost per affected child through age 10 years was $136 682 with a median of $74 924 because of a small number of extremely high cost children; costs were highest for pulmonary atresia with ventricular septal defect and hypoplastic left heart syndrome. Inpatient costs increased by 1.6% per year during the study period. A single birth year cohort (~50 000 births/year) had estimated expenditures of $11 902 899 through age 10 years. Extrapolating to the US population, inpatient costs for a single birth year cohort through age 10 years were ~$1 billion. CONCLUSIONS: Inpatient costs for CCHDs throughout childhood are high and rising. These revised estimates will contribute to comparative effectiveness research aimed at improving the value of care on a patient and population level.

Digoxin Use in Infants with Single Ventricle Physiology: Secondary Analysis of the Pediatric Heart Network Infant Single Ventricle Trial Public Use Dataset.

Digoxin has been associated with reduced interstage mortality after Norwood procedure. We sought to determine its association with survival and change in weight-for-age Z-score (WAZ) before the superior cavopulmonary connection (SCPC) surgery and at 14 months in a heterogeneous group of single ventricle infants. We performed a post-hoc analysis of the Pediatric Heart Network Infant Single Ventricle public use dataset to determine associations between digoxin and survival, transplant-free survival, and change in WAZ pre-SCPC and at 14 months. Sub-analyses of survival and transplant-free survival were performed for subjects who underwent Damus-Kaye-Stansel (DKS)/Norwood. Propensity score weighting was used in Cox hazard-proportion models. Of 229 subjects, 82 (36%) received digoxin and 147 (64%) received no digoxin. Pre-SCPC and 14-month survival and transplant-free survival were not significantly different between the digoxin and no digoxin groups for the main cohort and DKS/Norwood sub-group. However, in DKS/Norwood subjects there was a trend towards improved interstage transplant-free survival in the digoxin group (95.7 vs. 89.6%, p = 0.08). Digoxin was associated with a greater decrease in WAZ from birth to pre-SCPC (- 1.96 ± 0.19 vs. - 1.31 ± 0.18, p < 0.001) and birth to 14 months (- 0.64 ± 0.15 vs. - 0.19 ± 0.15, p = 0.03). Digoxin was not associated with improved survival during the interstage or at 14 months in a mixed single ventricle cohort, but there was a trend towards improved interstage transplant-free survival in post-Norwood infants. As digoxin was associated with poorer weight gain, further research is needed to identify the risks/benefits for anatomic subtypes of infants with single ventricles.