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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Diagnosis and Management of Myocarditis in Children: A Scientific Statement From the American Heart Association.

Myocarditis remains a clinical challenge in pediatrics. Originally, it was recognized at autopsy before the application of endomyocardial biopsy, which led to a histopathology-based diagnosis such as in the Dallas criteria. Given the invasive and low-sensitivity nature of endomyocardial biopsy, its diagnostic focus shifted to a reliance on clinical suspicion. With the advances of cardiac magnetic resonance, an examination of the whole heart in vivo has gained acceptance in the pursuit of a diagnosis of myocarditis. The presentation may vary from minimal symptoms to heart failure, life-threatening arrhythmias, or cardiogenic shock. Outcomes span full resolution to chronic heart failure and the need for heart transplantation with inadequate clues to predict the disease trajectory. The American Heart Association commissioned this writing group to explore the current knowledge and management within the field of pediatric myocarditis. This statement highlights advances in our understanding of the immunopathogenesis, new and shifting dominant pathogeneses, modern laboratory testing, and use of mechanical circulatory support, with a special emphasis on innovations in cardiac magnetic resonance imaging. Despite these strides forward, we struggle without a universally accepted definition of myocarditis, which impedes progress in disease-targeted therapy.

Pediatric Liver Transplant Survival in Alagille Syndrome Is Comparable to Biliary Atresia-A Linked Database Analysis.

OBJECTIVES: This study aims to report liver transplantation (LT) outcomes and cardiac disease manifestations in children with Alagille Syndrome (ALGS) in a contemporary cohort. METHODS: This project used a novel linkage between the Scientific Registry of Transplant Recipients and Pediatric Health Information System databases. All children ≤21 years undergoing a first LT were identified (2002-2018). The presence of ALGS was identified using Scientific Registry of Transplant Recipients diagnosis coding. Subjects with ALGS were age-matched 1:2 to LT recipients with biliary atresia (BA). The Kaplan-Meier method and log-rank test were used to compare patient and graft survival between groups. RESULTS: A total of 156 LT recipients with ALGS were identified and matched to a control group of 312 LT recipients with BA. Children with ALGS were more likely to have an associated diagnosis of congenital heart disease (80.7% vs 16.4%; P = 0.001) compared with children with BA with 40 (25.6%) children with AGS requiring cardiac intervention (catheter or surgical) either before or after LT. Those patients with ALGS had a higher creatinine, laboratory MELD, and PELD scores before LT. No difference was observed regarding patient or graft survival between children with ALGS and children with BA ( P = 0.08 and P = 0.27, respectively). CONCLUSIONS: Despite increased rate of congenital heart defects and cardiac interventions, higher creatinine, and higher laboratory MELD/PELD scores at time of transplant, this study demonstrates that there is no difference in either patient or graft survival between patients with ALGS and BA.

Cardiac magnetic resonance diastolic indices correlate with ventricular filling pressures in pediatric heart transplant recipients.

BACKGROUND: Atrial and ventricular filling pressures are routinely used in pediatric heart transplant (PHTx) recipients to assess graft function. We hypothesized that cardiac magnetic resonance (CMR) diastolic indices correlate with filling pressures, providing a noninvasive method of hemodynamic assessment. METHODS: Pediatric heart transplant recipients were prospectively enrolled at the time of cardiac catheterization. Pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) were measured. CMR included standard volumetric analysis. Filling curves were calculated by contouring every phase in the short-axis stack. Global longitudinal and circumferential strain (GLS, GCS) were calculated using feature tracking. Atrial volumes and ejection fraction were calculated from 4-chamber and 2-chamber cine images. Correlations were analyzed using Spearman's Rho; modeling was performed with multivariable logistic regression. RESULTS: A total of 35 patients with a mean age of 15.5 years were included, 12 with acute rejection. The median time post-transplant was 6.2 years. Peak filling rate (PFR) and peak LV ejection rate/end-diastolic volume (PER/EDV) correlated with PCWP (rho = 0.48 p = .005, and rho = -0.35 p = .046, respectively) as did GLS and GCS (rho = 0.52 p = .002, and 0.40 p = .01). Indexed maximum and minimum left atrial (LA) volume correlated with PCWP (rho = 0.41, p = .01, rho = 0.41 p = .01), and LA ejection fraction inversely correlated with PCWP (rho = -0.40, p = .02). GLS and GCS correlated with RAP (rho = 0.55, p = .001 and rho = 0.43, p = .01). A model including LV GLS and PFR estimated PCWP ≥12 mmHg with an area under the curve of 0.84. CONCLUSIONS: Cardiac magnetic resonance can be a useful noninvasive modality to assess for signs of diastolic dysfunction after PHTx.

Novel Cardiac Imaging Risk Score for Mortality Prediction in Duchenne Muscular Dystrophy.

Cardiovascular disease is the leading cause of death in patients with Duchenne Muscular Dystrophy (DMD), but there is significant cardiomyopathy phenotypic variability. Some patients demonstrate rapidly progressive disease and die at a young age while others survive into the fourth decade. Criteria to identify DMD subjects at greatest risk for early mortality could allow for increased monitoring and more intensive therapy. A risk score was created describing the onset and progression of left ventricular dysfunction and late gadolinium enhancement in subjects with DMD. DMD subjects prospectively enrolled in ongoing observational studies (which included cardiac magnetic resonance [CMR]) were used to validate the risk score. A total of 69 subjects had calculable scores. During the study period, 12 (17%) died from complications of DMD. The median risk score was 3 (IQR [2,5]; range [0,9]). The overall risk score applied at the most recent imaging age was associated with mortality at a median age of 17 years (IQR [16,20]) (HR 2.028, p < 0.001). There were no deaths in subjects with a score of less than two. Scores were stable over time. An imaging-based risk score allows risk stratification of subjects with DMD. This can be quickly calculated during a clinic visit to identify subjects at greatest risk of early death.

A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric hypertrophic cardiomyopathy to guide SCD prevention strategies. METHODS: In an international multicenter observational cohort study, phenotype-positive patients with isolated hypertrophic cardiomyopathy <18 years of age at diagnosis were eligible. The primary outcome variable was the time from diagnosis to a composite of SCD events at 5-year follow-up: SCD, resuscitated sudden cardiac arrest, and aborted SCD, that is, appropriate shock following primary prevention implantable cardioverter defibrillators. Competing risk models with cause-specific hazard regression were used to identify and quantify clinical and genetic factors associated with SCD. The cause-specific regression model was implemented using boosting, and tuned with 10 repeated 4-fold cross-validations. The final model was fitted using all data with the tuned hyperparameter value that maximizes the c-statistic, and its performance was characterized by using the c-statistic for competing risk models. The final model was validated in an independent external cohort (SHaRe [Sarcomeric Human Cardiomyopathy Registry], n=285). RESULTS: Overall, 572 patients met eligibility criteria with 2855 patient-years of follow-up. The 5-year cumulative proportion of SCD events was 9.1% (14 SCD, 25 resuscitated sudden cardiac arrests, and 14 aborted SCD). Risk predictors included age at diagnosis, documented nonsustained ventricular tachycardia, unexplained syncope, septal diameter z-score, left ventricular posterior wall diameter z score, left atrial diameter z score, peak left ventricular outflow tract gradient, and presence of a pathogenic variant. Unlike in adults, left ventricular outflow tract gradient had an inverse association, and family history of SCD had no association with SCD. Clinical and clinical/genetic models were developed to predict 5-year freedom from SCD. Both models adequately discriminated between patients with and without SCD events with a c-statistic of 0.75 and 0.76, respectively, and demonstrated good agreement between predicted and observed events in the primary and validation cohorts (validation c-statistic 0.71 and 0.72, respectively). CONCLUSION: Our study provides a validated SCD risk prediction model with >70% prediction accuracy and incorporates risk factors that are unique to pediatric hypertrophic cardiomyopathy. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision making for implantable cardioverter defibrillator insertion. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0403679.

Waitlist and Post-Heart Transplant Outcomes for Children with Kawasaki Disease in the United States.

We evaluated waitlist and post-heart transplant outcomes for children with Kawasaki disease and found that over 3 decades the number of patients requiring heart transplantation in the US is low. Also, patients with Kawasaki disease have similar waitlist and post-transplant outcomes compared with patients with dilated cardiomyopathy.

Impact of institutional routine surveillance endomyocardial biopsy frequency in the first year on rejection and graft survival in pediatric heart transplantation.

BACKGROUND: Routine surveillance biopsy (RSB) is performed to detect asymptomatic acute rejection (AR) after heart transplantation (HT). Variation in pediatric RSB across institutions is high. We examined center-based variation in RSB and its relationship to graft loss, AR, coronary artery vasculopathy (CAV), and cost of care during the first year post-HT. METHODS: We linked the Pediatric Health Information System (PHIS) and Scientific Registry of Transplant Recipients (SRTR, 2002-2016), including all primary-HT aged 0-21 years. We characterized centers by RSB frequency (defined as median biopsies performed among recipients aged ≥12 months without rejection in the first year). We adjusted for potential confounders and center effects with mixed-effects regression analysis. RESULTS: We analyzed 2867 patients at 29 centers. After adjusting for patient and center differences, increasing RSB frequency was associated with diagnosed AR (OR 1.15 p = 0.004), a trend toward treated AR (OR 1.09 p = 0.083), and higher hospital-based cost (US$390 315 vs. $313 248, p < 0.001) but no difference in graft survival (HR 1.00, p = 0.970) or CAV (SHR 1.04, p = 0.757) over median follow-up 3.9 years. Center RSB-frequency threshold of ≥2/year was associated with increased unadjusted rates of treated AR, but no association was found at thresholds greater than this. CONCLUSION: Center RSB frequency is positively associated with increased diagnosis of AR at 1 year post-HT. Graft survival and CAV appear similar at medium-term follow-up. We speculate that higher frequency RSB centers may have increased detection of clinically less important AR, though further study of the relationship between center RSB frequency and differences in treated AR is necessary.

Fontan-associated plastic bronchitis waitlist and heart transplant outcomes: A PHTS analysis.

Plastic bronchitis is a rare post-Fontan complication with limited treatment options. Heart transplantation has evolved as a potential curative option, but outcomes have not been well-defined. This study aims to assess contemporary waitlist and post-transplant outcomes in patients with plastic bronchitis. All Fontan patients were identified in the PHTS database (2010 - 2018). Waitlist and post-transplant outcomes were compared between Fontan patients with and without plastic bronchitis. Competing outcomes and Kaplan-Meier analyses were used to assess the impact of plastic bronchitis on waitlist and post-transplant survival. A secondary analysis excluded those with PLE from the comparison cohort. Of 645 Fontan patients listed for heart transplant, 69 (11%) had plastic bronchitis. At listing, patients with plastic bronchitis were younger (8.9 vs 11.1 years, P = .02), but had few other differences in baseline characteristics. A fewer Fontan patients with plastic bronchitis were listed in the more recent era (46 [15.4%] in 2010-2014 vs 23 [6.6%] in 2015-2018, P < .01). Overall, there was no difference in waitlist (P = .30) or post-transplant (P = .66) survival for Fontan patients with and without plastic bronchitis. The results were similar after excluding patients with PLE. Contrary to prior reports, this relatively large series showed that plastic bronchitis did not have a negative impact on survival to or after heart transplantation in Fontan patients. Our study also found a 50% reduction in listing in the current era, which may indicate evolution in management of Fontan patients.