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 > 7 days 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 17 years [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. J Heart Lung Transplant 2024;43:745-754 (c) 2024 International Society for Heart and Lung Transplantation. All rights reserved.

The aim of this study (CTOTC-09) was to assess the impact of “preformed” (at transplant) donor-specific anti-HLA antibody (DSA) and first year newly detected DSA (ndDSA) on allograft function at 3 years after pediatric heart transplantation (PHTx). We enrolled children listed at 9 North American centers. The primary end point was pulmonary capillary wedge pressure (PCWP) at 3 years posttransplant. Of 407 enrolled subjects, 370 achieved PHTx (mean age, 7.7 years; 57% male). Pre-PHTx sensitization status was nonsensitized (n = 163, 44%), sensitized/no DSA (n = 115, 31%), sensitized/DSA (n = 87, 24%), and insufficient DSA data (n = 5, 1%); 131 (35%) subjects developed ndDSA. Subjects with any DSA had comparable PCWP at 3 years to those with no DSA. There were also no significant differences overall between the 2 groups for other invasive hemodynamic measurements, systolic graft function by echocardiography, and serum brain natriuretic peptide concentration. However, in the multivariable analysis, persistent first-year DSA was a risk factor for 3-year abnormal graft function. Graft and patient survival did not differ between groups. In summary, overall, DSA status was not associated with worse allograft function or inferior patient and graft survival at 3 years, but persistent first-year DSA was a risk factor for late graft dysfunction.

IntroductionHeart 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. MethodsAn 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. ResultsThere 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. ConclusionFamilies of children who have undergone heart transplantation can incur significant out-of-pocket expenses and strategies to mitigate this financial burden should be investigated.

Introduction: We previously showed that highly sensitized and non-sensitized pediatric heart transplant (PHTx) recipients had similar 1 year survival (CTOTC-04 study). In this follow-up study (CTOTC-09), we assess risk factors for impaired allograft function at 3 years post-Tx including the impact of ‘preformed’ (at Tx) and first year newly detected donor specific antibodies (ndDSA). Methods: Consecutive children listed for Tx at 9 North American centers were prospectively enrolled. Management of sensitization, immunosuppression and rejection surveillance were standardized. The primary endpoint was pulmonary capillary wedge pressure (PCWP) at 3 years post-PHTx. Secondary endpoints included other hemodynamics measures, ejection fraction (EF), brain natriuretic peptide (BNP), graft and patient survival and rejection. DSA was defined as single antigen Luminex testing as ≥1 antibody specific to donor HLA antigens with MFI>1000 (based on core laboratory). Results: Of 407 children enrolled, 370 achieved PHTx (mean age 8.7 years). Sensitization status at PHTx was as follows: non-sensitized (n=163, 44%), sensitized/no DSA (n= 115, 31%), sensitized/DSA+ (n=87, 24%); unknown (n=5 (1%) unknown. Baseline characteristics among these groups differed significantly by ethnicity (p=0.024), height (p=0.017), weight (p=0.017), ICU admission (p=0.009), and prior sensitizing events (p=0.027). At 3 years, subjects with vs. without early DSA (preformed and/or first year ndDSA) had comparable PCWP, EF, and BNP levels (Figure). There were also no significant differences between the 2 groups for other hemodynamic measures (pulmonary artery, right atrial, and left and right ventricular end diastolic pressures, cardiac index, EF, and BNP level (all P >0.05). For the 3 sensitization status groups at Tx, the presence/absence of first year ndDSA also did not influence any of these endpoints. Freedom from death or retransplant was not influenced by sensitization status at Tx, though freedom from rejection with hemodynamic compromise was inferior in those with one or more DSA at Tx > 4000 MFI. Freedom from acute antibody mediated rejection was lowest in the non-sensitized group (p<0.001). Multivariable analyses showed that higher PCWP at 3 years post-Tx was associated with 3-year age (p=0.017), 3-year weight (0.001) and coronary artery disease (CAD, p=0.035) but not with DSA status (preformed and/or first year ndDSA). Adverse graft function was associated with weight (Odds Ratio (OR) 1.03; 95% confidence interval (CI) 1.02, 1.05; p<001); and any rejection with hemodynamic compromise (OR 7.91; 95% CI 1.37, 45.75; p=0.021) but not with DSA status. Conclusion: Sensitization status at PHTx and development of first year ndDSA are not associated with worse allograft function or inferior survival at 3 years. Ongoing follow-up, including assessment of CAD, continues. This information is critical for defining transplant strategies and the long-term impact of DSA on graft outcomes.

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.

Background Pediatric cardiomyopathy is a genetically heterogeneous disease with substantial morbidity and mortality. Current guidelines recommend genetic testing in children with hypertrophic, dilated, or restrictive cardiomyopathy, but practice variations exist. Robust data on clinical testing practices and diagnostic yield in children are lacking. This study aimed to identify the genetic causes of cardiomyopathy in children and to investigate clinical genetic testing practices. Methods and Results Children with familial or idiopathic cardiomyopathy were enrolled from 14 institutions in North America. Probands underwent exome sequencing. Rare sequence variants in 37 known cardiomyopathy genes were assessed for pathogenicity using consensus clinical interpretation guidelines. Of the 152 enrolled probands, 41% had a family history of cardiomyopathy. Of 81 (53%) who had undergone clinical genetic testing for cardiomyopathy before enrollment, 39 (48%) had a positive result. Genetic testing rates varied from 0% to 97% between sites. A positive family history and hypertrophic cardiomyopathy subtype were associated with increased likelihood of genetic testing ( P =0.005 and P =0.03, respectively). A molecular cause was identified in an additional 21% of the 63 children who did not undergo clinical testing, with positive results identified in both familial and idiopathic cases and across all phenotypic subtypes. Conclusions A definitive molecular genetic diagnosis can be made in a substantial proportion of children for whom the cause and heritable nature of their cardiomyopathy was previously unknown. Practice variations in genetic testing are great and should be reduced. Improvements can be made in comprehensive cardiac screening and predictive genetic testing in first‐degree relatives. Overall, our results support use of routine genetic testing in cases of both familial and idiopathic cardiomyopathy. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01873963.

Psychiatric disorders are common in pediatric HTx recipients. However, the impact of psychiatric comorbidities on patient outcomes is unknown. We aimed to assess the impact of disorders of adjustment, depression, and anxiety on HTx outcomes in children; hypothesizing that the presence of psychiatric disorders during or preceding HTx would negatively impact outcomes. All pediatric HTx recipients ≥8 years of age who survived to hospital discharge were identified from a novel linkage between the PHIS and SRTR databases (2002‐2016). Psychiatric disorders were identified using ICD codes during or preceding the HTx admission. Post‐transplant graft survival, freedom from readmission, and freedom from rejection were analyzed using the Kaplan‐Meier method. Multivariable Cox proportional hazard models were used to adjust for covariates. A total of 1192 patients were included, of which 133 (11.2%) had depression, 197 (16.5%) had anxiety, and 218 (18.3%) had adjustment disorders. The presence of depression was independently associated with higher rates of readmission (60.9% vs 54.1% at 6 months) (AHR 1.63, 95% CI 1.22‐2.18, P = .001) and inferior graft survival (70.2% vs 83.4% at 5 years) (AHR 1.62, 95% CI 1.14‐2.3, P = .007). Anxiety was independently associated with higher rates of readmission (60.4% vs 53.9% at 6 months) (AHR 1.46, 95% CI 1.09‐1.94, P = .01). Anxiety and depression in the pretransplant period are independently associated with outcomes following HTx in children. Evaluation and management of psychiatric comorbidities represents an important component of care in this vulnerable population.

Rehospitalization following pediatric heart transplantation is common. However, existing data remain somewhat limited. Using a novel linkage between administrative and clinical databases, pediatric heart transplant (HT) recipients from 29 centers who survived to discharge were retrospectively reviewed to determine the frequency, timing of, and indication for all-cause rehospitalizations in the year following transplant discharge. Of 2870 pediatric HT recipients, 1835 (63.9%) were rehospitalized in the first year post-discharge (5429 total readmissions). Rehospitalization rates varied significantly across centers (46% to 100%) and were inversely correlated to center transplant volume (r(2) 0.25, p < 0.01). The median number of rehospitalizations per patient was 2 (IQR 1-4) and the median time to first rehospitalization was 29 days (IQR 9-99 days). Independent risk factors for rehospitalization included younger age at HT (HR 0.99, 95% CI 0.97-0.99), congenital heart disease (HR 1.2, 95% CI 1.1-1.4), listing status 1B at transplant (HR 1.3, 95% CI 1.1-1.5), and post-transplant complications including rejection prior to discharge (HR 1.5 95% CI 1.3-1.8) and chylothorax (HR 1.3, 95% CI 1.0-1.6). Cardiac diagnoses were the most common indication for rehospitalization (n = 1600, 29.5%), followed by infection (n = 1367, 25.2%). These findings may serve to guide the development of interventions aimed at reducing post-HT hospitalizations.

Introduction: Pediatric heart transplant recipients (PHTx) undergo frequent surveillance endomyocardial biopsies (EMB). Non-invasive screening for acute rejection (AR) could decrease morbidity, improve quality of life, and decrease healthcare costs. Hypothesis: We hypothesized that cardiac magnetic resonance (CMR) extracellular volume (ECV), native T1, and T2 mapping can detect AR in PHTx. Methods: PHTx (n=29) were prospectively enrolled at two sites at time of surveillance EMB or EMB for AR. AR was defined as a clinical change or positive EMB requiring intensification of immunosuppression. Subjects with cardiac allograft vasculopathy (n=3) were excluded; ECV was not measured in 2 subjects without rejection (no IV, poor breathholds). CMR without sedation included standard volumetrics, modified Look-Locker inversion recovery before and after contrast, and T2 mapping. A Wilcoxon rank sum was used to assess for a difference between groups. Results: Median age was 17 y/o (range 9-19). There were 9 subjects with and 17 subjects without AR. Base ECV, mid ECV, 4-ch ECV, and average ECV were increased in AR vs non-rejection (Table 1, Fig 1). Native T1 and T2 times were also increased in patients with AR (Table 1). A cut-off of 29% for mid ECV and 1070ms for mid native T1 identifies all patients with rejection with 6 false positive results in non-rejection (Fig 1) and could potentially decrease the need for EMB by 65%. Conclusions: ECV, native T1, and T2 mapping can non-invasively distinguish between PHTx with and without AR and have potential to decrease the required number of surveillance EMBs.

Children with EA have similar outcomes after HT when compared with all types of CHD. Therefore, HT should remain a consideration if otherwise indicated in this population.

Purpose Readmission is common following pediatric heart transplantation (HT), based on existing single center data. The nationwide incidence of rehospitalization after HT has not been reported. We aimed to assess the incidence, risk factors, and indications for rehospitalization in pediatric HT recipients using a nationwide multicenter linked database. Methods The Scientific Registry of Transplant Recipients and Pediatric Health Information System databases were linked at the patient level using indirect identifiers (2002-2016). All pediatric HT recipients who survived to discharge were included. The frequency, timing of, and indication for all-cause readmissions in the first year following initial discharge were assessed. Multivariable logistic regression examined risk factors for readmission with standard error estimates adjusted for clustering within centers. Results A total of 2870 HT recipients from 29 centers were included. Of these, 1835 (63.9%) were readmitted within the first post-HT year (total of 5428 admissions). Readmission rates varied across transplant centers from 46% (1 center) to 100% (3 centers). For patients who were rehospitalized, the median number of readmissions was 2 (IQR 1-4) and the median time to first readmission was 29 days (IQR 9-99 days). Risk factors independently associated with readmission included age <4 years at HT (AOR 1.3, 95%CI 1.1-1.6), congenital heart disease (AOR 1.4, 95%CI 1.1-1.7), rejection prior to discharge (AOR 1.9 95%CI 1.4-2.5), history of chylothorax (1.7, 95%CI 1.0-2.8) and post-HT length of stay >30 days (AOR 1.4, 95%CI 1.1-1.9). Cardiac diagnoses, including rejection and/or concern for rejection, were the most common indications for readmission (N=2213, 40.8%), followed by infection/fever (N=1222, 22.5%), and respiratory diagnoses (N=393, 7.2%). Conclusion Rehospitalization is common in the first year following pediatric HT, with considerable variation in readmission rates across centers. Younger age, congenital heart disease, and a more complicated post-HT course increase the risk for subsequent readmission. Risk stratification based on these factors may serve to guide decision-making in determining discharge readiness and planning.

Right ventricular (RV) failure is a potentially fatal complication following heart transplantation (HTx). Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that is used to decrease pulmonary vascular resistance immediately post-HTx to reduce the risk of RV failure. The aim of this study was to describe utilization patterns, costs, and outcomes associated with post-transplant iNO use in children. All pediatric HTx recipients (2002-2016) were identified from a unique linked PHIS/SRTR dataset. Post-HTx iNO use was determined based on hospital billing data. Utilization patterns and associated costs were described. The association of iNO support with post-HTx survival was assessed using the Kaplan-Meier method and a multivariable Cox proportional hazards model was used to adjust for risk factors. A total of 2833 pediatric HTx recipients from 28 centers were identified with 1057 (36.5%) receiving iNO post-HTx. Post-HTx iNO use showed significant increase overall (17.2-54.7%, p<0.001) and wide variation among centers (9-100%, p<0.001). Patients with congenital heart disease (aOR 1.4, 95% CI 1.2, 1.6), requiring mechanical ventilation at HTx (aOR 1.3, 95% CI 1.1, 1.6), and pre-transplant iNO (aOR 9.3, 95% CI 5.4, 16) were more likely to receive iNO post-HTx. The median daily cost of iNO was $2617 (IQR $1843-$3646). Patients who required>5days of iNO post-HTx demonstrated inferior 1-year post-HTx survival (p<0.001) and iNO use>5days was independently associated with worse post-HTx survival (AHR 1.6, 95% CI 1.2, 2.1; p<0.001). There is wide variation in iNO use among centers following pediatric HTx with use increasing over time despite significant incremental cost. Prolonged iNO use post-HTx is associated with worse survival, likely serving as a marker of residual illness severity. Further research is needed to define the populations that derive the greatest benefit from this costly therapy.

DiGeorge syndrome (DGS) is commonly associated with both congenital heart disease (CHD) and immunologic abnormalities. While CHD may prompt consideration for heart transplantation (HTx), little is known about HTx management or outcomes in this group. The aim of this study was to describe the spectrum of patients with DGS who undergo HTx and report post-HTx outcomes. All pediatric HTx recipients (2002–2016) with DGS were identified using ICD codes from a linked billing and clinical registry database. Patient characteristics and outcomes were described and compared to non-DGS HTx recipients with CHD. Kaplan–Meier methods were used to assess overall survival, freedom from infection, and freedom from rejection. A total of 17 patients with DGS who underwent HTx at 12 different centers were included. Median age at HTx was 5 years (IQR 0–13 years). Steroids were used for induction in all patients in addition to thymoglobulin in 13/17 (76%) and IL2R antagonists in 3/17 (18%). Maintenance immunosuppression was a combination of tacrolimus or cyclosporine and mycophenolate or azathioprine in 16/17 (94%). Half received steroids at the time of discharge. There were six deaths (35%). The median post-HTx survival was 5.4 years with no difference in freedom from rejection, infection, or overall survival between patients with and without DGS. Patients with DGS undergoing HTx received standard immunosuppression. We found no difference in freedom from infection, rejection, or overall post-HTx survival compared to non-DGS patients, although the small size of our study resulted in limited statistical power. Given the potential for favorable outcomes, patients with DGS may be considered for HTx in the appropriate clinical setting.

OBJECTIVE:To assess the prevalence of psychiatric disorders and associated therapies in children during their heart transplantation admission. STUDY DESIGN:All pediatric heart transplant recipients (1999-2016) were included from a linked administrative and clinical registry database. Psychiatric disorders and associated therapies were identified using International Classification of Diseases or billing codes during the transplant admission. Data were analyzed using standard descriptive statistics. Multivariable logistic regression assessed factors independently associated with psychiatric disorders or therapies. RESULTS:A total of 3073 pediatric heart transplant recipients were included. Psychiatric disorders were present in 434 (14.1%) patients during the heart transplant admission, with adjustment disorders being the most common. Antidepressant therapy was prescribed to 212 patients (6.9%) and selective serotonin reuptake inhibitors were most commonly used. Psychiatric diagnoses (8.4% vs 18.1%; P < .001) and the use of antidepressants (4.5% vs 8.9%; P < .001) increased over time (era 1, 1999-2009 vs era 2, 2010-2016). Psychiatric disorders were present in 39.8% of patients ≥8 years of age requiring ventricular assist device support at heart transplantation. The need for ventricular assist device support was independently associated with psychiatric diagnoses (aOR, 1.57; 95% CI, 1.18-2.1; P = .002) and antidepressant therapy (aOR, 2.11; 95% CI. 1.43-3.12; P < .001). CONCLUSIONS:Psychiatric disorders are common in pediatric heart transplant recipients, especially among those bridged with ventricular assist device support. Psychiatric diagnoses and the use of antidepressants has increased over time, likely representing improved recognition of psychiatric comorbidities in this vulnerable population. Access to psychiatric services represents an important component of the multidisciplinary team caring for pediatric heart transplant recipients.

Primary graft dysfunction following HTx is associated with significant morbidity and mortality. This study aimed to assess the incidence of, risk factors for, and outcomes of children requiring ECMO within 24 hours of HTx. This study utilized a linked PHIS/SRTR database of pediatric HTx recipients (2002‐2016). Post‐HTx ECMO was identified using inpatient billing data. Logistic regression assessed risk factors for post‐HTx ECMO. Kaplan‐Meier analyses assessed in‐hospital mortality and post‐discharge survival. A total of 2820 patients were included with 224 (7.9%) requiring ECMO. Independent risk factors for post‐HTx ECMO include age <1 year (aOR: 2.2, 95% CI: 1.3‐3.7, P = 0.006) or 1‐5 years (aOR: 2.1, 95% CI: 1.3‐3.4, P = 0.002), and ECMO support at HTx (aOR: 27.4, 95% CI: 15.2‐49.6, P < 0.001). Survival to discharge decreased with increasing duration of post‐HTx ECMO support; 89% for 1‐3 days, 79.1% for 4‐6 days, 63.2% for 7‐9 days, and 18.8% for ≥10 days. There was no difference in long‐term survival for patients requiring post‐HTx ECMO who survived to hospital discharge (P = 0.434). There are identifiable risk factors associated with the need for ECMO in the post‐HTx period. Length of time on ECMO post‐HTx is strongly associated with the risk of in‐hospital mortality. Patients who require ECMO early post‐HTx and survive to discharge have comparable outcomes to patients who did not require ECMO.

Background: Cardiomyopathies are a rare cause of pediatric heart disease, but they are one of the leading causes of heart failure admissions, sudden death, and need for heart transplant in childhood. Reports from the Pediatric Cardiomyopathy Registry (PCMR) have shown that almost 40% of children presenting with symptomatic cardiomyopathy either die or undergo heart transplant within 2 years of presentation. Little is known regarding circulating biomarkers as predictors of outcome in pediatric cardiomyopathy. Study design: The Cardiac Biomarkers in Pediatric Cardiomyopathy (PCM Biomarkers) study is a multi-center prospective study conducted by the PCMR investigators to identify serum biomarkers for predicting outcome in children with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Patients < 21 years of age with either DCM or HCM were eligible. Those with DCM were enrolled into cohorts based on time from cardiomyopathy diagnosis: categorized as new onset or chronic. Clinical endpoints included sudden death and progressive heart failure. Results: There were 288 children diagnosed at a mean age of 7.2 +/- 6.3 years who enrolled in the PCM Biomarkers Study at a median time from diagnosis to enrollment of 1.9 years. There were 80 children enrolled in the new onset DCM cohort, defined as diagnosis at or 12 months prior to enrollment. The median age at diagnosis for the new onset DCM was 1.7 years and median time from diagnosis to enrollment was 0.1 years. There were 141 children enrolled with either chronic DCM or chronic HCM, defined as children >= 2 years from diagnosis to enrollment. Among children with chronic cardiomyopathy, median age at diagnosis was 3.4 years and median time from diagnosis to enrollment was 4.8 years. Conclusion: The PCM Biomarkers study is evaluating the predictive value of serum biomarkers to aid in the prognosis and management of children with DCM and HCM. The results will provide valuable information where data are lacking in children.

INTRODUCTION:Myocardial strain measurements are increasingly used to detect complications following heart transplantation. However, the temporal association of these changes with allograft rejection is not well defined. The aim of this study was to describe the evolution of strain measurements prior to the diagnosis of rejection in paediatric heart transplant recipients.METHODS:All paediatric heart transplant recipients (2004-2015) with at least one episode of acute rejection were identified. Longitudinal and circumferential strain measurements were assessed at the time of rejection and retrospectively on all echocardiograms until the most recent negative biopsy. Smoothing technique (LOESS) was used to visualise the changes of each variable over time and estimate the time preceding rejection at which alterations are first detectable.RESULTS:A total of 58 rejection episodes were included from 37 unique patients. In the presence of rejection, there were decrements from baseline in global longitudinal strain (-18.2 versus -14.1), global circumferential strain (-24.1 versus -19.6), longitudinal strain rate (-1 versus -0.8), circumferential strain rate (-1.3 versus -1.1), peak longitudinal early diastolic strain rate (1.3 versus 1), and peak circumferential early diastolic strain rate (1.5 versus 1.3) (p<0.01 for all). The earliest detectable changes occurred 45 days prior to rejection with simultaneous alterations in myocardial strain and ejection fraction.CONCLUSIONS:Changes in graft function can be detected non-invasively prior to the diagnosis of rejection. However, changes in strain occur concurrently with a decline in ejection fraction. Strain measurements aid in the non-invasive detection of rejection, but may not facilitate earlier diagnosis compared to more traditional measures of ventricular function.

OBJECTIVES:To compare the outcomes and comorbidities of children with mitochondrial disease undergoing heart transplantation with children without mitochondrial disease. STUDY DESIGN:Using a unique linkage between the Pediatric Health Information System and Scientific Registry of Transplant Recipients databases, pediatric heart transplantation recipients from 2002 to 2016 with a diagnosis of cardiomyopathy were included. Post heart transplantation survival and morbidities were compared between patients with and without mitochondrial disease. RESULTS:A total of 1330 patients were included, including 47 (3.5%) with mitochondrial disease. Survival after heart transplantation was similar between patients with and without mitochondrial disease over a median follow-up of 4 years. Patients with mitochondrial disease were more likely to have a stroke after heart transplantation (11% vs 3%; P = .009), require a longer duration of mechanical ventilation after heart transplantation (3 days vs 1 day; P < .001), and have a longer intensive care unit stay after heart transplantation (10 vs 6 days; P = .007). The absence of a hospital readmission within the first post-transplant year was similar among patients with and without mitochondrial disease (61.7% vs 51%; P = .14). However, patients with mitochondrial disease who were readmitted demonstrated a longer length of stay compared with those without (median, 14 days vs 8 days; P = .03). CONCLUSIONS:Patients with mitochondrial disease can successfully undergo heart transplantation with survival comparable with patients without mitochondrial disease. Patients with mitochondrial disease have greater risk for post-heart transplantation morbidities including stroke, prolonged mechanical ventilation, and longer intensive care unit and readmission length of stay. These results suggest that the presence of mitochondrial disease should not be an absolute contraindication to heart transplantation in the appropriate clinical setting.