Treatment Strategies for Cardiomyopathy in Children: A Scientific Statement From the American Heart Association.

This scientific statement from the American Heart Association focuses on treatment strategies and modalities for cardiomyopathy (heart muscle disease) in children and serves as a companion scientific statement for the recent statement on the classification and diagnosis of cardiomyopathy in children. We propose that the foundation of treatment of pediatric cardiomyopathies is based on these principles applied as personalized therapy for children with cardiomyopathy: (1) identification of the specific cardiac pathophysiology; (2) determination of the root cause of the cardiomyopathy so that, if applicable, cause-specific treatment can occur (precision medicine); and (3) application of therapies based on the associated clinical milieu of the patient. These clinical milieus include patients at risk for developing cardiomyopathy (cardiomyopathy phenotype negative), asymptomatic patients with cardiomyopathy (phenotype positive), patients with symptomatic cardiomyopathy, and patients with end-stage cardiomyopathy. This scientific statement focuses primarily on the most frequent phenotypes, dilated and hypertrophic, that occur in children. Other less frequent cardiomyopathies, including left ventricular noncompaction, restrictive cardiomyopathy, and arrhythmogenic cardiomyopathy, are discussed in less detail. Suggestions are based on previous clinical and investigational experience, extrapolating therapies for cardiomyopathies in adults to children and noting the problems and challenges that have arisen in this experience. These likely underscore the increasingly apparent differences in pathogenesis and even pathophysiology in childhood cardiomyopathies compared with adult disease. These differences will likely affect the utility of some adult therapy strategies. Therefore, special emphasis has been placed on cause-specific therapies in children for prevention and attenuation of their cardiomyopathy in addition to symptomatic treatments. Current investigational strategies and treatments not in wide clinical practice, including future direction for investigational management strategies, trial designs, and collaborative networks, are also discussed because they have the potential to further refine and improve the health and outcomes of children with cardiomyopathy in the future.

Thrombocytopenia is Associated with Higher Fontan Pressure and Increased Morbidity in Patients with Fontan Circulation.

After the Fontan procedure, patients require lifelong follow-up due to significant late morbidity and mortality. Thrombocytopenia is seen frequently post-Fontan, likely due to secondary hypersplenism from elevated Fontan pressure. We investigated platelet counts in patients with a Fontan circulation and assessed associations with catheterization data and clinical outcomes. This retrospective study included 92 patients (33% female) post-Fontan who had a complete blood count performed between January 2011 and July 2023. The age at evaluation was 24.0 ± 8.9 years. Outcomes measured included elevated Fontan pressure (≥ 15 mmHg), Fontan-associated liver disease (FALD), unscheduled admissions, transplant, and death. Participants with thrombocytopenia (≤ 150,000/µL) had significantly higher rates of elevated Fontan pressure (OR 8.1, 95% CI 1.3-52.7, p = 0.03), FALD (OR 4.1, 95% CI 1.6-10.6, p = 0.004), and unscheduled admissions (362 ± 577 versus 115 ± 185 admissions per 1000 patient-years, p = 0.02). Thrombocytopenia post-Fontan is associated with elevated Fontan pressure, FALD, and increased morbidity. Platelet count could serve as a non-invasive factor in identifying patients at risk of decompensation.

Distinct association between chronic Epstein-Barr virus infection and T cell compartments from pediatric heart, kidney, and liver transplant recipients.

Chronic Epstein-Barr virus (EBV) infection after pediatric organ transplantation (Tx) accounts for significant morbidity and mortality. The risk of complications, such as posttransplant lymphoproliferative disorders, in high viral load (HVL) carriers is the highest in heart Tx recipients. However, the immunologic signatures of such a risk have been insufficiently defined. Here, we assessed the phenotypic, functional, and transcriptomic profiles of peripheral blood CD8+/CD4+ T cells, including EBV-specific T cells, in 77 pediatric heart, kidney, and liver Tx recipients and established the relationship between memory differentiation and progression toward exhaustion. Unlike kidney and liver HVL carriers, heart HVL carriers displayed distinct CD8+ T cells with (1) up-regulation of interleukin-21R, (2) decreased naive phenotype and altered memory differentiation, (3) accumulation of terminally exhausted (TEX PD-1+T-bet-Eomes+) and decrease of functional precursors of exhausted (TPEX PD-1intT-bet+) effector subsets, and (4) transcriptomic signatures supporting the phenotypic changes. In addition, CD4+ T cells from heart HVL carriers displayed similar changes in naive and memory subsets, elevated Th1 follicular helper cells, and plasma interleukin-21, suggesting an alternative inflammatory mechanism that governs T cell responses in heart Tx recipients. These results may explain the different incidences of EBV complications and may help improve the risk stratification and clinical management of different types of Tx recipients.

Impact of donor-specific anti-HLA antibody on cardiac hemodynamics and graft function 3 years after pediatric heart transplantation: First results from the CTOTC-09 multi-institutional study.

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.

Cardiac imaging and biomarkers for assessing myocardial fibrosis in children with hypertrophic cardiomyopathy.

BACKGROUND: Myocardial fibrosis, as diagnosed on cardiac magnetic resonance imaging (cMRI) by late gadolinium enhancement (LGE), is associated with adverse outcomes in adults with hypertrophic cardiomyopathy (HCM), but its prevalence and magnitude in children with HCM have not been established. We investigated: (1) the prevalence and extent of myocardial fibrosis as detected by LGE cMRI; (2) the agreement between echocardiographic and cMRI measurements of cardiac structure; and (3) whether serum concentrations of N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) and cardiac troponin-T are associated with cMRI measurements. METHODS: A cross-section of children with HCM from 9 tertiary-care pediatric heart centers in the U.S. and Canada were enrolled in this prospective NHLBI study of cardiac biomarkers in pediatric cardiomyopathy (ClinicalTrials.gov Identifier: NCT01873976). The median age of the 67 participants was 13.8 years (range 1-18 years). Core laboratories analyzed echocardiographic and cMRI measurements, and serum biomarker concentrations. RESULTS: In 52 children with non-obstructive HCM undergoing cMRI, overall low levels of myocardial fibrosis with LGE >2% of left ventricular (LV) mass were detected in 37 (71%) (median %LGE, 9.0%; IQR: 6.0%, 13.0%; range, 0% to 57%). Echocardiographic and cMRI measurements of LV dimensions, LV mass, and interventricular septal thickness showed good agreement using the Bland-Altman method. NT-proBNP concentrations were strongly and positively associated with LV mass and interventricular septal thickness (P < .001), but not LGE. CONCLUSIONS: Low levels of myocardial fibrosis are common in pediatric patients with HCM seen at referral centers. Longitudinal studies of myocardial fibrosis and serum biomarkers are warranted to determine their predictive value for adverse outcomes in pediatric patients with HCM.

Short-term clinical outcomes and predicted cost savings of dd-cfDNA-led surveillance after pediatric heart transplantation.

BACKGROUND: Endomyocardial biopsy (EMB)-led surveillance is common after pediatric heart transplantation (HT), with some centers performing periodic surveillance EMBs indefinitely after HT. Donor derived cell-free DNA (dd-cfDNA)-led surveillance offers an alternative, but knowledge about its clinical and economic outcomes, both key drivers of potential utilization, are lacking. METHODS: Using single-center recipient and center-level data, we describe clinical outcomes prior to and since transition from EMB-led surveillance to dd-cfDNA-led surveillance of pediatric and young adult HT recipients. These data were then used to inform Markov models to compare costs between EMB-led and dd-cfDNA-led surveillance strategies. RESULTS: Over 34.5 months, dd-cfDNA-led surveillance decreased the number of EMBs by 81.8% (95% CI 76.3%-86.5%) among 120 HT recipients (median age 13.3 years). There were no differences in the incidences of graft loss or death among all recipients followed at our center prior to and following implementation of dd-cfDNA-led surveillance (graft loss: 2.9 vs. 1.5 per 100 patient-years; p = .17; mortality: 3.7 vs. 2.2 per 100 patient-years; p = .23). Over 20 years from HT, dd-cfDNA-led surveillance is projected to cost $8545 less than EMB-led surveillance. Model findings were robust in sensitivity and scenario analyses, with cost of EMB, cost of dd-cfDNA testing, and probability of elevated dd-cfDNA most influential on model findings. CONCLUSIONS: dd-cfDNA-led surveillance shows promise as a less invasive and cost saving alternative to EMB-led surveillance among pediatric and young adult HT recipients.

Longitudinal Assessment of Cardiac Function Following Multisystem Inflammatory Syndrome in Children Associated with COVID-19.

Multisystem inflammatory syndrome in children (MIS-C) after COVID-19 is commonly associated with cardiac involvement. Studies found myocardial dysfunction, as measured by decreased ejection fraction and abnormal strain, to be common early in illness. However, there is limited data on longitudinal cardiac outcomes. We aim to describe the evolution of cardiac findings in pediatric MIS-C from acute illness through at least 2-month follow-up. A retrospective single-center review of 36 patients admitted with MIS-C from April 2020 through September 2021 was performed. Echocardiographic data including cardiac function and global longitudinal strain (GLS) were analyzed at initial presentation, discharge, 2-4-week follow-up, and at least 2-month follow-up. Patients with mild and severe disease, normal and abnormal left ventricular ejection fraction (LVEF), and normal and abnormal GLS at presentation were compared. On presentation, 42% of patients with MIS-C had decreased LVEF < 55%. In patients in whom GLS was obtained (N = 18), 44% were abnormal (GLS < |- 18|%). Of patients with normal LVEF, 22% had abnormal GLS. There were no significant differences in troponin or brain natriuretic peptide between those with normal and abnormal LVEF. In most MIS-C patients with initial LVEF < 55% (90%), LVEF normalized upon discharge. At 2-month follow-up, all patients had normal LVEF with 21% having persistently abnormal GLS. Myocardial systolic dysfunction and abnormal deformation were common findings in MIS-C at presentation. While EF often normalized by 2 months, persistently abnormal GLS was more common, suggesting ongoing subclinical dysfunction. Our study offers an optimistic outlook for recovery in patients with MIS-C and carditis, however ongoing investigation for longitudinal effects is warranted.

Multimodality Imaging in Ebstein Anomaly.

Ebstein anomaly is the most common form of tricuspid valve congenital anomalies. The tricuspid valve is abnormal with different degrees of displacement of the septal leaflet and abnormal rotation of the valve towards the right ventricular outflow tract. In severe forms, it results in significant tricuspid regurgitation and requires surgical repair. There is an increased interest in understanding the anatomy of the tricuspid valve in this lesion as the surgical repair has evolved with the invention and wide adoption of the cone operation. Multimodality imaging plays an important role in diagnosis, follow-up, surgical planning and post-operative care. This review provides anatomical tips for the cardiac imagers caring for patients with Ebstein anomaly and will help provide image-based personalized medicine.

mRNA Coronavirus Disease 2019 Vaccine-Associated Myopericarditis in Adolescents: A Survey Study.

In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions.

A homozygous CAP2 pathogenic variant in a neonate presenting with rapidly progressive cardiomyopathy and nemaline rods.

Nemaline Myopathy (NM) is a disorder of skeletal muscles caused by mutations in sarcomere proteins and characterized by accumulation of microscopic rod or thread-like structures (nemaline bodies) in skeletal muscles. Patients diagnosed with both NM and infantile cardiomyopathy are very rare. A male infant presented, within the first few hours of life, with severe dilated cardiomyopathy, biventricular dysfunction and left ventricular noncompaction. A muscle biopsy on the 8th day of life from the right sternocleidomastoid muscle identified nemaline rods. Whole exome sequencing identified a c.1288 delT (homozygous pathogenic variant) in the CAP2 gene (NM_006366), yielding a CAP2 protein (NP_006357.1) with a p.C430fs. Both parents were heterozygous for the same variant but have no history of heart or muscle disease. Analysis of patient derived fibroblasts and cardiomyocytes derived from induced pluripotent stem cells confirmed the p.C430fs mutation (pathogenic variant), which appears to cause loss of both CAP2 protein and mRNA. The CAP2 gene encodes cyclase associated protein 2, an actin monomer binding and filament depolymerizing protein and CAP2 knockout mice develop severe dilated cardiomyopathy and muscle weakness. The patient underwent a heart transplant at 1 year of age. Heart tissue explanted at that time also showed nemaline rods and additionally disintegration of the myofibrillar structure. Other extra cardiac concerns include mild hypotonia, atrophic and widened scarring. This is the first description of a patient presenting with nemaline myopathy associated with a pathogenic variant of CAP2.

Responsiveness to second and third dose of mRNA COVID-19 vaccination in adolescent and young adult heart transplant recipients.

BACKGROUND: Third-dose mRNA COVID-19 vaccine is currently recommended in the United States for SOT recipients based in part on data showing diminished immune response, including Ab production, after a two-dose regimen. Data on vaccine response in adolescent and young adult SOT recipients are limited, including no data reported on third-dose responsiveness. METHODS: Results of serologic testing in a convenience sample of 28 vaccinated adolescent and young adult HT recipients at a single institution were collected from the medical record and summarized. RESULTS: At a median of 98.5 days (IQR 59-150) after second dose, 17 (61%) had an Ab response. Among 12 who had serology before and after third-dose vaccination, four of seven who were negative prior to third dose became positive at a median of 34 days (IQR 31-39.5) following third dose. No myocarditis, acute rejection, graft dysfunction, graft loss, or deaths were observed. CONCLUSIONS: These findings support recommendations for the routine administration of three doses of mRNA vaccines in adolescent and young adult HT recipients and show a potential subpopulation in whom the fourth dose should be contemplated.

Early findings after integration of donor-derived cell-free DNA into clinical care following pediatric heart transplantation.

BACKGROUND: Endomyocardial biopsy (EMB) is costly and discomforting yet remains a key component of surveillance after pediatric heart transplantation (HT). Donor-derived cell-free DNA (dd-cfDNA) has been histologically validated with high negative predictive value, offering an alternative to surveillance EMB (sEMB). METHODS: We implemented an alternative surveillance protocol using commercially available dd-cfDNA assays in place of sEMB after pediatric HT. Recipients ≧7 months post-HT with reassuring clinical assessment were referred for dd-cfDNA. When not elevated above the manufacturers' threshold, sEMB was deferred. Subsequent clinical status and results of follow-up EMB were analyzed. RESULTS: Over 17 months, 58 recipients [34% female, median age at HT 3.1 years (IQR 0.6-10.6)] had dd-cfDNA assessed per protocol. Median age was 14.8 years (8.4-18.3) and time from HT 6.0 years (2.2-11.2). Forty-seven (81%) had non-elevated dd-cfDNA and 11 (19%) were elevated. During a median of 8.7 months (4.2-15), all are alive without allograft loss/new dysfunction. Among those with non-elevated dd-cfDNA, 24 (51%) had subsequent sEMB at 12.1 months (6.9-12.9) with 23 showing no acute rejection (AR): grade 0R/pAMR0 (n = 16); 1R(1A)/pAMR0 (n = 7). One had AR (grade 2R(3A)/pAMR0) on follow-up sEMB after decreased immunosuppression following a diagnosis of PTLD. All 11 with elevated dd-cfDNA had reflex EMB at 19 days (12-32) with AR in 4: grade 1R(1B-2)/pAMR0 (n = 3); 1R(1B)/pAMR2 (n = 1). CONCLUSIONS: dd-cfDNA assessment in place of selected, per-protocol EMB decreased surveillance EMB by 81% in our pediatric HT recipient cohort with no short-term adverse outcomes. Individual center approach to surveillance EMB will influence the utility of these findings.

Electrocardiogram changes in pediatric patients with myocarditis.

BACKGROUND: It is traditionally taught that pediatric patients with myocarditis almost always have an abnormal electrocardiogram (ECG) at presentation. However, there has never been a study to objectively evaluate ECG changes in pediatric myocarditis patients compared to healthy controls or explore if specific ECG changes correlate with clinical outcomes. METHODS: Pediatric patients diagnosed with acute myocarditis were age and sex matched 1:2 with healthy controls in this retrospective case-control study spanning a seven-year period. ECGs from presentation through discharge were interpreted by electrophysiologists blinded to the patients' diagnoses. RESULTS: Thirty-nine patients with myocarditis were identified. Twenty-eight (72%) had an abnormal ECG at presentation, 11 (28%) had a completely normal ECG. In this second group, six patients had an abnormal ECG at some point during their hospital course for a total of 34 (88%). Myocarditis patients who had an abnormal ECG at presentation spent more time in the hospital, 5 (2-19) versus 2 ((1-3) days (p < 0.01), and in the ICU, 1 (0-6) versus 0 (0-1) days (p < 0.01). Myocarditis patients were more likely to have ST elevation on their ECG compared to control patients (41% versus 17%, p < 0.01). Patients with ST elevation at presentation had a higher peak troponin level, 18.4 (5.8-31.0) versus 7.7 (0-19.1) ng/ml, (p < 0.01). CONCLUSIONS: Over a quarter of patients with myocarditis had a normal ECG at presentation to the emergency department. Patients with an abnormal ECG at presentation spent more time in the hospital. The presenting ECG, particularly the presence of ST elevation, may correlate with other clinical markers and help direct early management decisions.

Cardiac MRI-Derived Inferior Vena Cava Cross-Sectional Area Correlates with Measures of Fontan-Associated Liver Disease.

There is currently no clear consensus on screening techniques to evaluate the presence or severity of Fontan-associated liver disease (FALD). Cardiac MRI (CMR) is used routinely for post-Fontan surveillance, but CMR-derived measures that relate to the severity of FALD are not yet defined. This was a cross-sectional single-center study of post-Fontan patients who underwent a CMR. CMR exams were re-analyzed by a single pediatric cardiologist. Surrogates of FALD included Gamma-Glutamyl Transferase (GGT), Fibrosis-4 laboratory score (FIB-4), and imaging findings. Findings consistent with cirrhosis on liver ultrasound included increased liver echogenicity and/or nodularity. Statistical analyses were performed to investigate potential relationships between CMR parameters and markers of FALD. Sixty-one patients were included. A larger inferior vena cava cross-sectional area (IVC-CSA) indexed to height was significantly associated with a higher FIB-4 score (Spearman's ρ = 0.28, p = 0.04), a higher GGT level (Spearman's ρ = 0.40, p = 0.02), and findings consistent with cirrhosis on liver ultrasound (OR 1.17, 95% CI: (1.01, 1.35), p = 0.04). None of the other CMR parameters were associated with markers of FALD. A larger indexed IVC-CSA was associated with higher systemic ventricle end-diastolic pressure (EDP) on cardiac catheterization (Spearman's ρ = 0.39, p = 0.018) as well as older age (Spearman's ρ = 0.46, p = < 0.001). Indexed IVC-CSA was the only CMR parameter that was associated with markers of FALD. This measure has the potential to serve as an additional non-invasive tool to improve screening strategies for FALD. Visual abstract summarizing the primary findings of this paper.

Successful orthotopic heart transplantation in CPTII deficiency.

Carnitine palmitoyl transferase II (CPT II) catalyzes the release of activated long-chain fatty acids from acylcarnitines into mitochondria for subsequent fatty acid oxidation. Depending on residual enzyme activity, deficiency of this enzyme leads to a spectrum of symptoms from early onset hypoglycemia, hyperammonemia, cardiomyopathy and death to onset of recurrent rhabdomyolysis in adolescents and young adults. We present a case of successful orthotopic heart transplantation in a patient with severe infantile onset cardiomyopathy due to CPT II deficiency identified through newborn screening. Excellent cardiac function is preserved 12 years post-transplantation; however, the patient has developed intermittent episodes of hyperammonemia and rhabdomyolysis later in childhood and early adolescence readily resolved with intravenous glucose. Successful heart transplant in this patient demonstrates the feasibility of this management option in patients with even severe forms of long chain fatty acid oxidation disorders.

Bartonella henselae infection in the pediatric solid organ transplant recipient.

Bartonella henselae infection can cause a wide spectrum of diseases in both the immunocompetent and immunocompromised host with BA a severe form relegated to immunocompromised hosts, including solid organ transplant population. There are established criteria for diagnosis of Bartonella infection based on clinical presentation, serologic testing, imaging studies and, when indicated, tissue sampling for histopathological evaluation, particularly for BA. However, treatment recommendations for BA are inconclusive. Furthermore, there are no studies in the pediatric solid organ transplant population for antimicrobial therapy during BA secondary to Bartonella henselae infection. A case of BA following heart transplant is presented along with a literature review of clinical presentation; diagnosis and therapy for BA in the pediatric solid organ transplant population.

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.

Establishing Baseline Metrics of Heart Failure Medication Use in Children: A Collaborative Effort from the ACTION Network.

Heart failure metrics specific to the pediatric population are required to successfully implement quality improvement initiatives in children with heart failure. Medication use at the time of discharge following admission for decompensated heart failure has been identified as a potential quality metric in this population. This study aimed to report medication use at discharge in the current era for children admitted with acute decompensated heart failure. All patients < 21 years of age with an index admission (1/1/2011-12/31/2019) for acute heart failure and a coexisting diagnosis of cardiomyopathy were identified from the Pediatric Health Information System. Medication use patterns were described and compared across age groups and centers. A total of 2288 patients were identified for inclusion. An angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker (ACEi/ARB) was prescribed in 1479 (64.6%), beta blocker in 1132 (49.5%), and mineralocorticoid receptor antagonist (MRA) in 864 (37.8%) patients at discharge. The use of ACEi/ARB at discharge has decreased over time (64.6% vs. 69.6%, p = 0.001) and the use of beta blockers has increased (49.5% vs. 36.8%, p < 0.001) compared to a historical cohort (2001-2010). There is considerable variability in medication use across centers with an overall increase in beta blocker and decrease in ACEi/ARB use over time. Collaborative efforts are needed to standardize care and define quality metrics to identify best practices in the management of pediatric heart failure.

Heart Transplantation in Children with Mitochondrial Disease.

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.