Genetic Testing Resources and Practice Patterns Among Pediatric Cardiomyopathy Programs.

The use of genetic testing has enhanced the diagnostic accuracy of heritable genetic cardiomyopathies. However, it remains unclear how genetic information is interpreted and incorporated into clinical practice for children with cardiomyopathy. The primary aim of this study was to understand how clinical practice differs regarding sequence variant classifications amongst pediatric cardiologists who treat children with cardiomyopathy. A secondary aim was to understand the availability of genetic testing and counseling resources across participating pediatric cardiomyopathy programs. An electronic survey was distributed to pediatric heart failure, cardiomyopathy, or heart transplantation physicians between August and September 2022. A total of 106 individual providers from 68 unique centers responded to the survey. Resources for genetic testing and genetic counseling vary among large pediatric cardiomyopathy programs. A minority of centers reported having a geneticist (N = 16, 23.5%) or a genetic counselor (N = 21, 31%) on faculty within the division of pediatric cardiology. A total of 9 centers reported having both (13%). Few centers (N = 13, 19%) have a formal process in place to re-engage patients who were previously discharged from cardiology follow-up if variant reclassification would alter clinical management. Clinical practice patterns were uniform in response to pathogenic or likely pathogenic variants but were more variable for variants of uncertain significance. Efforts to better incorporate genetic expertise and resources into the clinical practice of pediatric cardiomyopathy may help to standardize the interpretation of genetic information and better inform clinical decision-making surrounding heritable cardiomyopathies.

"In-patient echocardiography utilization post repair of congenital heart disease. Analysis of data from the Pediatric Health Information System from 2010 to 2019".

BACKGROUND: Echocardiography is a key diagnostic tool for medical decision-making following congenital heart surgery. Overall utilisation of echocardiography for specific congenital heart lesions following cardiac surgery has not previously been reported. This study aims to assess echocardiogram utilisation following the surgical repair of CHD to describe the variation in use across centres and provide clinical benchmarks. METHODS: All patients < 18 years of age undergoing surgical repair of CHD were identified from the Pediatric Health Information System from 2010 to 2019. Surgeries were grouped based on their Risk Adjustment for Congenital Heart Surgery-1 scores. Detailed billing data were used to assess the frequency/cost of post-operative echocardiograms, phase of hospital care, and hospital length of stay. RESULTS: In total, 37,238 surgical encounters were identified for inclusion across 48 centres. Higher Risk Adjustment for Congenital Heart Surgery scores were associated with an increased median number of post-operative echocardiograms (2 versus 4 in Risk Adjustment for Congenital Heart Surgery score 1 versus 6, p < 0.001), and longer median post-operative length of stay (3 days versus 31 days in Risk Adjustment for Congenital Heart Surgery score 1 versus 6, p < 0.001). After accounting for surgical complexity, there was significant variability in echocardiogram utilisation across centres (median daily echocardiogram utilisation range 0.2/day-0.6/day, p < 0.001). There is no difference in the proportion of patients with high surgical complexity (Risk Adjustment for Congenital Heart Surgery ≥ 4) between centres with high versus low echocardiogram utilisation (p = 0.44). CONCLUSIONS: Increasing surgical complexity is associated with longer post-operative length of stay and increased utilisation of echocardiography. There is wide variability in echocardiography resource utilisation across centres, even when accounting for surgical complexity.

Research Gaps in Pediatric Heart Failure: Defining the Gaps and Then Closing Them Over the Next Decade.

Given the numerous opportunities and the wide knowledge gaps in pediatric heart failure, an international group of pediatric heart failure experts with diverse backgrounds were invited and tasked with identifying research gaps in each pediatric heart failure domain that scientists and funding agencies need to focus on over the next decade.

Cardiac magnetic resonance assessment of acute rejection and cardiac allograft vasculopathy in pediatric heart transplant.

BACKGROUND: In pediatric heart transplant (PHT), cardiac catheterization with endomyocardial biopsy (EMB) is standard for diagnosing acute rejection (AR) and cardiac allograft vasculopathy (CAV) but is costly and invasive. OBJECTIVES: To evaluate the ability of cardiac magnetic resonance (CMR) to noninvasively identify differences in PHT patients with AR and CAV. METHODS: Patients were enrolled at three children's hospitals. Data were collected from surveillance EMB or EMB for-cause AR. Patients were excluded if they had concurrent diagnoses of AR and CAV, CMR obtained >7days from AR diagnosis, they had EMB negative AR, or could not undergo contrasted, unsedated CMR. Kruskal-Wallis test was used to compare groups: (1) No AR or CAV (Healthy), (2) AR, (3) CAV. Wilcoxon rank-sum test was used for pairwise comparisons. RESULTS: Fifty-nine patients met inclusion criteria (median age 17years [IQR 15-19]) 10 (17%) with AR, and 11 (19%) with CAV. AR subjects had worse left ventricular ejection fraction compared to Healthy patients (p = 0.001). Global circumferential strain (GCS) was worse in AR (p = 0.054) and CAV (p = 0.019), compared to Healthy patients. ECV, native T1, and T2 z-scores were elevated in patients with AR. CONCLUSIONS: CMR was able to identify differences between CAV and AR. CAV subjects had normal global function but abnormal GCS which may suggest subclinical dysfunction. AR patients have abnormal function and tissue characteristics consistent with edema (elevated ECV, native T1 and T2 z-scores). Characterization of CMR patterns is critical for the development of noninvasive biomarkers for PHT and may decrease dependence on EMB.

Association of Digoxin Use With Transplant-Free Interstage Survival in Infants Palliated With a Stage 1 Hybrid Procedure.

Background Digoxin prescription in patients with single-ventricle physiology after stage 1 palliation is associated with reduced interstage death. Prior literature has primarily included patients having undergone the Norwood procedure. We sought to determine if digoxin prescription at discharge in infants following hybrid stage 1 palliation was associated with improved transplant-free interstage survival. Methods and Results A retrospective multicenter cohort analysis was conducted using data from the National Pediatric Cardiology Quality Improvement Collaborative registry data from 2008 to 2021. Infants with functional single ventricles and aortic arch obstruction discharged home after the hybrid stage 1 palliation hospitalization were included. Patients were excluded if they had supraventricular tachycardia or conversion to Norwood operation. The primary outcome was transplant-free survival. Multivariable logistic regression analysis including a propensity score for digoxin use identified associations between digoxin use and interstage death or transplant. Of 259 included infants from 45 sites, 158 (61%) had hypoplastic left heart syndrome. Forty-nine percent had a gestational age ≤38 weeks, 18% had a birth weight <2.5 kg, and 58% had a preoperative risk factor. Of the 259 subjects, 129 (50%) were discharged on digoxin. Interstage death or transplant occurred in 30 (23%) patients in the no-digoxin group compared with 18 (14%) in the digoxin group (P=0.06). With multivariate analysis, discharge digoxin prescription was associated with a lower risk of interstage death or transplant (adjusted odds ratio, 0.48 [95% CI, 0.24-0.93]; P=0.03). Conclusions In infants with single-ventricle physiology who underwent hybrid stage 1 palliation, digoxin prescription at hospital discharge was associated with improved interstage transplant-free survival.

Variation in Inhaled Medication Use for Infants With Congenital Heart Disease and Bronchiolitis.

BACKGROUND AND OBJECTIVES: Current viral bronchiolitis guidelines exclude infants with congenital heart disease (CHD). Variations in the use of common therapeutics in this population and their associations with clinical outcomes are unknown. Our objective was to evaluate variations in (1) the use of ß-2-agonists and hypertonic saline across hospitals among infants with CHD hospitalized with bronchiolitis, and (2) hospital-level associations between medication use and outcomes. METHODS: We performed a multicenter retrospective cohort study using administrative data from 52 hospitals in the Pediatric Health Information System. We included infants ≤12 months old hospitalized from January 1, 2015 to June 30, 2019 for bronchiolitis with a secondary diagnosis of CHD. Primary exposures were the hospital-level proportion of days that patients received ß-2-agonists or hypertonic saline. Linear regression models assessed the association between the primary exposure and length of stay, 7-day readmission, mechanical ventilation use, and ICU utilization, adjusting for patient covariates and accounting for clustering by center. RESULTS: We identified 6846 index hospitalizations for bronchiolitis in infants with CHD. Overall, 43% received a ß-2-agonist, and 23% received hypertonic saline. The proportion of days with the use of ß-2-agonists (3.6% to 57.4%) and hypertonic saline (0.0% to 65.8%) varied widely across hospitals in our adjusted model. For both exposures, adjusted models revealed no association between days of use and patient outcomes. CONCLUSIONS: For children with CHD hospitalized with bronchiolitis, hospital-level use of ß-2-agonists and hypertonic saline varied widely, and their use was not associated with clinical outcomes.

Narrative review of pediatric heart failure in the age of precision medicine.

Background and Objective: Improvement in the affordability and convenience of genetic testing has rapidly expanded the understanding of the mechanistic causes of various pediatric cardiomyopathies. Concurrently, new therapies are being developed to better-target specific pathologies as opposed to classic therapies that treat the maladaptive processes of chronic heart failure. This review will discuss the advances in genetic testing and specific therapies that have been shown to benefit or potentially benefit genetically distinct subsets of the pediatric population with heart failure or at risk of developing heart failure. Methods: We undertook a comprehensive database search (January 2000-August 2022) of PubMed, utilizing terms 'pediatric', 'cardiomyopathy', 'heart failure', 'genetics', and 'precision medicine'. Additional notable studies were obtained from ClinicalTrials.gov. Studies published in English that examine genetic basis and treatment modalities of pediatric heart failure. Key Content and Findings: New and investigational therapies for hypertrophic cardiomyopathies associated with obstruction or Noonan syndrome, Fabry cardiomyopathy, Barth syndrome, Duchenne muscular dystrophy, single ventricle failure, and heart failure in specific demographics are discussed. Conclusions: The rapid expansion of the genetic understanding of cardiomyopathy and heart failure as well as tailored therapies to specific molecular causes holds great promise for the future of pediatric heart failure treatment. Whereas conventional heart failure therapies target the maladaptive remodeling response that leads to worsening of heart failure, these therapies target the molecular causes of cardiomyopathy and heart failure in certain populations allowing for a potential to more significantly impact the clinical trajectory of pediatric heart failure.

Out-of-pocket expenses associated with pediatric heart transplantation.

INTRODUCTION: Heart transplantation in children is associated with high resource utilization. However, the financial burden on families and the association with patient and demographic factors remains unclear. This study aims to examine out-of-pocket expenses associated with pediatric heart transplantation. METHODS: An anonymous REDCap survey was distributed to caregivers of children who have undergone heart transplantation using social media, national organizations, and during clinic encounters from May through August 2022. RESULTS: There were a total of 146 respondents. The median monthly out-of-pocket expense was $250 (IQR $75-$500) and 20 respondents (13.7%) reported monthly expenses of >$1000. Families with commercial insurance reported significantly higher out-of-pocket expenses compared to those with government-sponsored insurance (median $350 vs. $100, p < .001). Families with government-sponsored insurance were most happy with their insurance coverage, followed by commercial insurance and then coverage through the Affordable Care Act (p < .001 for all pairwise comparisons). There was no statistically significant difference in overall transplant-related out-of-pocket expenses based on total household income (p = .222). Monthly out-of-pocket expense was not associated with the number of medications, type of immunosuppressants, or post-transplant complications including rejection, PTLD, or CAV (p = NS for all). Cardiac catheterizations and unplanned admissions were reported as the events that incurred the highest out-of-pocket expense. CONCLUSION: Families of children who have undergone heart transplantation can incur significant out-of-pocket expenses and strategies to mitigate this financial burden should be investigated.

The impact of donor consent mechanism on organ procurement organization performance in the United States.

BACKGROUND: Lack of donor organ availability represents a major limitation to the success of solid organ transplantation. The Scientific Registry of Transplant Recipients (SRTR) publishes performance reports of organ procurement organizations (OPO) in the United States, but does not stratify by the mechanism of donor consent, namely first-person authorization (organ donor registry) and next-of-kin authorization. This study aimed to report the trends in deceased organ donation in the United States and assess the regional differences in OPO performance after accounting for the different mechanisms of donor consent. METHODS: The SRTR database was queried for all eligible deaths (2008-2019) which were then stratified based on the mechanism of donor authorization. Multivariable logistic regression was performed to assess the probability of organ donation across OPOs based on specific donor consent mechanisms. Eligible deaths were divided into 3 cohorts based on the probability to donate. Consent rates at the OPO level were calculated for each cohort. RESULTS: Organ donor registration among adult eligible deaths in the U.S. increased over time (2008: 10% vs 2019: 39%, p < 0.001), coincident with a decline in next-of-kin authorization rates (2008: 70% vs 2019: 64%, p < 0.001). At the OPO level, the increased organ donor registration was associated with lower next-of-kin authorization rates. Among eligible deaths with medium- and low-probability of donation, recruitment was highly variable across OPO's, ranging from 36% to 75% in the medium-probability group (median 54%, IQR 50%-59%) and 8% and 73% in the low-probability group (median 30%, IQR 17%-38%). CONCLUSION: Significant variability exists across OPOs in the consent of potentially persuadable donors after adjusting for population demographic differences and the mechanism of consent. Current metrics may not truly reflect OPO performance as they do not account for consent mechanism. There is further opportunity for improvement in deceased organ donation through targeted initiatives across OPOs, modeled after regions with the best performance.

Risk of Sudden Death in Patients With RASopathy Hypertrophic Cardiomyopathy.

BACKGROUND: Genetic defects in the RAS/mitogen-activated protein kinase pathway are an important cause of hypertrophic cardiomyopathy (RAS-HCM). Unlike primary HCM (P-HCM), the risk of sudden cardiac death (SCD) and long-term survival in RAS-HCM are poorly understood. OBJECTIVES: The study's objective was to compare transplant-free survival, incidence of SCD, and implantable cardioverter-defibrillator (ICD) use between RAS-HCM and P-HCM patients. METHODS: In an international, 21-center cohort study, we analyzed phenotype-positive pediatric RAS-HCM (n = 188) and P-HCM (n = 567) patients. The between-group differences in cumulative incidence of all outcomes from first evaluation were compared using Gray's tests, and age-related hazard of all-cause mortality was determined. RESULTS: RAS-HCM patients had a lower median age at diagnosis compared to P-HCM (0.9 years [IQR: 0.2-5.0 years] vs 9.8 years [IQR: 2.0-13.9 years], respectively) (P < 0.001). The 10-year cumulative incidence of SCD from first evaluation was not different between RAS-HCM and P-HCM (4.7% vs 4.2%, respectively; P = 0.59). The 10-year cumulative incidence of nonarrhythmic deaths or transplant was higher in RAS-HCM compared with P-HCM (11.0% vs 5.4%, respectively; P = 0.011). The 10-year cumulative incidence of ICD insertions, however, was 5-fold lower in RAS-HCM compared with P-HCM (6.9% vs 36.6%; P < 0.001). Nonarrhythmic deaths occurred primarily in infancy and SCD primarily in adolescence. CONCLUSIONS: RAS-HCM was associated with a higher incidence of nonarrhythmic death or transplant but similar incidence of SCD as P-HCM. However, ICDs were used less frequently in RAS-HCM compared to P-HCM. In addition to monitoring for heart failure and timely consideration of advanced heart failure therapies, better risk stratification is needed to guide ICD practices in RAS-HCM.

Perceptions of pediatric deceased donor consent: A survey of organ procurement organizations.

BACKGROUND: Children awaiting transplantation face a high risk of waitlist mortality due to a shortage of pediatric organ donors. Pediatric donation consent rates vary across Organ Procurement Organizations (OPOs), suggesting that some OPOs might utilize more effective pediatric-focused donor recruitment techniques than others. An online survey of 193 donation requestor staff sheds light on the strategies that OPO staff utilize when approaching potential pediatric deceased organ donors. METHODS: In collaboration with the Association of Organ Procurement Organizations, the research team contacted the executive directors and medical directors of all 57 of the OPOs in the US. Of these, 51 OPOs agreed to participate, and 47 provided contact information for donation requestor staff. Of the 379 staff invited to participate in the survey, 193 provided complete responses. RESULTS: Respondents indicated more comfort approaching adult donors than pediatric donors, and they endorsed approach techniques that were interpersonal and emotional rather than professional and informative. Respondents were accurate in their perceptions about which donor characteristics are associated with consent. However, respondents from OPOs with high consent rates (according to data from the Scientific Registry of Transplant Recipients), and those from OPOs with low consent rates were very similar in terms of demographics, training, experience, and reported techniques. CONCLUSIONS: Additional research is needed to better determine why some OPOs have higher consent rates than others and whether the factors that lead to high consent rates in high-performing OPOs can be successful when implemented by lower-performing OPOs.

Incidence of and risk factors for influenza-associated hospital encounters in pediatric solid organ transplant recipients.

Few studies have defined the incidence of and risk factors for influenza infection in pediatric solid organ transplant (SOT) recipients. We used a linkage between the Pediatric Health Information System and the Scientific Registry of Transplant Recipients databases to identify posttransplant influenza-associated hospital encounters (IAHEs) in pediatric SOT recipients of single-organ transplants. Among 7997 unique pediatric SOT recipients transplanted between January 01, 2006, and January 06, 2016, estimated 1- and 3-year posttransplant cumulative incidence rates of IAHEs were 2.7% (95% CI, 2.4%-3.1%) and 7.4% (95% CI, 6.8%-8.0%), respectively. One- and 3-year cumulative incidence rates of severe IAHEs were 0.3% (95% CI, 0.2%-0.5%) and 0.9% (95% CI, 0.7%-1.2%), respectively. Multivariable analysis showed that the organ type (adjusted subdistribution hazard ratio [aSHR]-kidney: reference, liver: 0.64 [95% CI, 0.49-0.84], and heart: 0.72 [95% CI, 0.57-0.93]), race/ethnicity (aSHR-non-Hispanic White: reference, non-Hispanic Black: 1.63 [95% CI, 1.29-2.07], Hispanic 1.57 [95% CI, 1.27-1.94]), and increasing age at transplant (aSHR, 0.93 [95% CI, 0.91-0.94]) were significantly associated with IAHE occurrence. Heart transplant recipients had a near statistically significant increase in hazard for severe IAHE (aSHR 1.96 [0.92-3.49]). Our findings may help guide future influenza prevention efforts and facilitate intervention impact assessment measurement in pediatric SOT recipients.

Machine Learning to Predict Interstage Mortality Following Single Ventricle Palliation: A NPC-QIC Database Analysis.

There is high risk of mortality between stage I and stage II palliation of single ventricle heart disease. This study aimed to leverage advanced machine learning algorithms to optimize risk-prediction models and identify features most predictive of interstage mortality. This study utilized retrospective data from the National Pediatric Cardiology Quality Improvement Collaborative and included all patients who underwent stage I palliation and survived to hospital discharge (2008-2019). Multiple machine learning models were evaluated, including logistic regression, random forest, gradient boosting trees, extreme gradient boost trees, and light gradient boosting machines. A total of 3267 patients were included with 208 (6.4%) interstage deaths. Machine learning models were trained on 180 clinical features. Digoxin use at discharge was the most influential factor resulting in a lower risk of interstage mortality (p < 0.0001). Stage I surgery with Blalock-Taussig-Thomas shunt portended higher risk than Sano conduit (7.8% vs 4.4%, p = 0.0002). Non-modifiable risk factors identified with increased risk of interstage mortality included female sex, lower gestational age, and lower birth weight. Post-operative risk factors included the requirement of unplanned catheterization and more severe atrioventricular valve insufficiency at discharge. Light gradient boosting machines demonstrated the best performance with an area under the receiver operative characteristic curve of 0.642. Advanced machine learning algorithms highlight a number of modifiable and non-modifiable risk factors for interstage mortality following stage I palliation. However, model performance remains modest, suggesting the presence of unmeasured confounders that contribute to interstage risk.

Acute-on-chronic liver failure before liver transplantation does not impact post-transplant survival in children with biliary atresia.

Acute-on-chronic liver failure (ACLF) occurs in children with biliary atresia (BA) awaiting liver transplantation (LT). However, data on transplant outcomes in ACLF are limited. Our aim was to characterize ACLF and determine its effect on transplant outcome and resource utilization. Using a linkage of the Scientific Registry of Transplant Recipients and Pediatric Health Information System, we identified children with BA between 3 months and 18 years at the time of listing who received a transplant from 2003 to 2018 and were hospitalized while waiting. ACLF was defined by the presence of at least 1 extra-hepatic organ failure during a pre-LT hospitalization. In all, 1044 patients (58% female, median age at listing 7.0 months IQR 5.0-14.0) were included. Thirty-four percent (351/1044) of the patients had at least 1 ACLF hospitalization. Patients with ACLF had longer waitlist times (114 [54-231] vs. 81 [35-181] days, p < 0.001), and were more likely to be listed as Status 1 (8% vs. 4%, p = 0.02). Pre-LT resource utilization was significantly higher in ACLF patients. There were no differences in mortality at 30 days (ACLF 3% vs. No ACLF 2%, p = 0.17), 90 days (ACLF 3% vs. No ACLF 2%, p = 0.24), 1 year (ACLF 3% vs. No ACLF 2%, p =0.23), 3 years (ACLF 4% vs. No ACLF 3%, p = 0.58), or 5 years (ACLF 5% vs. No ACLF 4%, p = 0.38) after LT. ACLF status was not associated with increased post-transplant mortality (adjusted HR 1.51, 95% CI 0.76-3.0, p =0.25). ACLF is an important morbidity in children with BA awaiting LT as it is associated with higher resource utilization and longer waitlist times. Further studies are needed to help understand the spectrum of ACLF and better prioritize critically ill children awaiting LT, as our study shows successful post-LT outcomes in children with BA and ACLF.

Cardiac anomalies in Axenfeld-Rieger syndrome.

Axenfeld-Rieger syndrome is a rare multi-system disorder associated with cardiac anomalies. All patients with a diagnosis of Axenfeld-Rieger syndrome were identified from our electronic medical record. Chart review was performed to document the presence and types of CHD. Out of 58 patients, 14 (24.1%) had CHD and a wide variety of cardiac lesions were identified.

Early aspirin use and the development of cardiac allograft vasculopathy in pediatric heart transplant recipients: A pediatric heart transplant society analysis.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains a leading cause of graft loss in pediatric heart transplant (HTx) recipients. Adult literature suggests that aspirin (ASA) use in the early post-HTx period may reduce the risk of CAV. This study aimed to determine the impact of early ASA use on the development of CAV in pediatric HTx recipients. METHODS: All subjects <17 years of age at time of primary HTx who survived ≥3 years without evidence of CAV were identified for inclusion from the Pediatric Heart Transplant Society database (1996-2019). Early ASA use was defined as ASA started within the first 3 years post-HTx and was classified as continuous or intermittent. Frequency of ASA use was described across centers. Kaplan-Meier method assessed freedom from CAV and overall graft survival. Multiphase parametric hazard analyses and propensity score matched analysis were used to identify independent risk factors. RESULTS: 3,011 patients were included with 387 (13%) receiving continuous ASA, 676 (22%) receiving intermittent ASA, and 1,948 (65%) receiving no ASA. ASA use was highly variable across centers (0%-100%). At baseline patients receiving continuous ASA therapy demonstrated inferior graft survival (p < 0.001) and worse freedom from CAV (p = 0.002), but with lower CAV grades (p = 0.05). In multiphase parametric hazard modeling continuous ASA use was not independently associated with CAV, but remained associated with inferior graft survival. Propensity-matched sub-analysis between continuous and no ASA groups demonstrated no difference in freedom from CAV or overall graft loss. CONCLUSIONS: ASA use varies widely across pediatric HTx centers. Early ASA use did not reduce the risk of CAV or graft loss in pediatric heart transplant recipients.

The Prevalence and Association of Exercise Test Abnormalities With Sudden Cardiac Death and Transplant-Free Survival in Childhood Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, abnormal results on exercise stress testing are predictive of heart failure outcomes. Our goal was to determine whether an abnormal exercise response is associated with adverse outcomes in pediatric patients with HCM. METHODS: In an international cohort study including 20 centers, phenotype-positive patients with primary HCM who were <18 years of age at diagnosis were included. Abnormal exercise response was defined as a blunted blood pressure response and new or worsened ST- or T-wave segment changes or complex ventricular ectopy. Sudden cardiac death (SCD) events were defined as a composite of SCD and aborted sudden cardiac arrest. Using Kaplan-Meier survival, competing outcomes, and Cox regression analyses, we analyzed the association of abnormal exercise test results with transplant and SCD event-free survival. RESULTS: Of 724 eligible patients, 630 underwent at least 1 exercise test. There were no major differences in clinical characteristics between those with or without an exercise test. The median age at exercise testing was 13.8 years (interquartile range, 4.7 years); 78% were male and 39% were receiving beta-blockers. A total of 175 (28%) had abnormal test results. Patients with abnormal test results had more severe septal hypertrophy, higher left atrial diameter z scores, higher resting left ventricular outflow tract gradient, and higher frequency of myectomy compared with participants with normal test results (P<0.05). Compared with normal test results, abnormal test results were independently associated with lower 5-year transplant-free survival (97% versus 88%, respectively; P=0.005). Patients with exercise-induced ischemia were most likely to experience all-cause death or transplant (hazard ratio, 4.86 [95% CI, 1.69-13.99]), followed by those with an abnormal blood pressure response (hazard ratio, 3.19 [95% CI, 1.32-7.71]). Exercise-induced ischemia was also independently associated with lower SCD event-free survival (hazard ratio, 3.32 [95% CI, 1.27-8.70]). Exercise-induced ectopy was not associated with survival. CONCLUSIONS: Exercise abnormalities are common in childhood HCM. An abnormal exercise test result was independently associated with lower transplant-free survival, especially in those with an ischemic or abnormal blood pressure response with exercise. Exercise-induced ischemia was also independently associated with SCD events. These findings argue for routine exercise testing in childhood HCM as part of ongoing risk assessment.

Neonates with acute liver failure have higher overall mortality but similar posttransplant outcomes as older infants.

Neonatal acute liver failure (ALF) carries a high mortality rate; however, little data exist on its peritransplant hospital course. This project aimed to identify factors associated with outcomes in neonates with ALF using large multicenter databases. Patients with International Classification of Diseases, Ninth Revision/International Classification of Diseases, Tenth Revision codes for liver failure (2004-2018) from linked Pediatric Health Information System and Scientific Registry of Transplant Recipients databases were assigned to two groups: neonates aged ≤30 days or older infants aged 31-120 days at admission. Billing data were used to assign diagnoses and assess patient comorbidities (sepsis, extracorporeal membrane oxygenation, total parenteral nutrition, intensive care unit, and cardiac/renal/respiratory failure). Statistical analysis included Kaplan-Meier survival curve analysis and univariate and multivariate analyses with the Cox proportional hazards model. We identified 1807 neonates and 890 older infants. Neonates had significantly lower survival to 90 days ( p = 0.04) and a lower rate of liver transplantation (2.0% vs. 6.4%; p < 0.001). Common risk factors associated with death or transplant were present between groups: diagnosis, respiratory failure, cardiac failure, and renal failure. Among neonates versus older infants who received a transplant, there was no significant differences in posttransplant lengths of stay (median 38 vs. 32 days; p = 0.53), posttransplant mortality (15% vs. 11%; p = 0.66), or graft loss (9.7% vs. 8.1%; p = 0.82). We present the largest multicenter study on peritransplant outcomes in neonatal ALF and show similar risk factors for death or transplant in neonates compared with older infants. Despite lower transplantation rates, neonates demonstrate similar posttransplant outcomes as older infants. Further studies are needed to better risk stratify neonates eligible for transplant and improve outcomes.

Vendor independent myocardial strain values in children.

BACKGROUND: Two-dimensional (2D) strain imaging has become an important tool in assessing subclinical myocardial dysfunction in children. However, there are no published normal values for vendor-independent strain software. The aim of this study was to estimate 2D strain values in a cohort of healthy children using Tomtec cardiac performance analysis (CPA), a vendor-independent software. METHODS: Transthoracic echocardiograms of healthy pediatric outpatients (0-18 years) were retrospectively analyzed from the Vanderbilt Pediatric Heart Institute using CPA. The cardiac assessment included global longitudinal strain (GLS), global longitudinal strain rate (GLSR), global circumferential strain (GCS), and global circumferential strain rate (GCSR). Mean strain values with standard deviation (SD) are reported. The Wilcoxon rank sum test, linear regression, and one-way analysis of variance were used to assess differences among the various groups. RESULTS: Among 142 children analyzed, 79 (56%) were male, and the median age was 5.5 (range, 0-18) years. The mean (SD) strain values were GLS -19.3 ± 3.4, GLSR -1.1 ± .22; GCS -24.7 ± 4.3, GCSR -1.5 ± .28. Age accounted for <8% of the variation in GLS, GCS, and GCSR. However, for GLSR, there was a statistically significant difference between younger and older age groups with higher GLSR in the younger age group. Age accounted for ∼25% of the variation in GLSR (R2  = .25, p < 0.001). There were no significant differences in strain based on sex. CONCLUSION: We report normal myocardial strain values in healthy children by age for strain using CPA. These values add to the growing body of literature on myocardial strain in children and provide necessary data for the interpretation of strain imaging.