An in vitro comparison of intra-operative isohemagglutinin and human leukocyte antigen removal techniques in pediatric heart transplantation.

BACKGROUND: Highly sensitized pediatric patients awaiting heart transplantation experience longer wait times and thus higher waitlist mortality. Similarly, children less than 2 years of age have increased waitlist times and mortality when compared to their older peers. To improve the likelihood of successful transplantation in these patients, various strategies have been utilized, including peri-operative plasmapheresis. However, limited data exists comparing plasmapheresis techniques for antibody reduction. This study's aim was to compare the in vitro magnitude of isohemagglutinin titers (IT) and human leukocyte antigen (HLA) antibody removal and the time required between membrane-based plasmapheresis (MP) and centrifuge-based plasmapheresis (CP) incorporated into the extracorporeal (EC) circuit. METHODS: Two MP (Prismaflex) and two CP (Spectra Optia, Terumo BCT) circuits were incorporated into four separate EC circuits primed with high titer, highly sensitized type O donor whole blood. Assays were performed to determine baseline IT and anti-HLA antibodies and then at 30-minute increments until completion of the run (two plasma volume exchanges) at two hours. RESULTS: There was a decrease in anti-A and anti-B IgM and IgG titers with both MP and CP. Mean anti-A and anti-B titer reduction was by 4.625 titers (93.7% change) and 4.375 titers (93.8% change) using MP and CP, respectively. At 2 h of apheresis, CP reduced 62.5% of all ITs to ≤ 1:4, while MP reduced 50% of ITs to ≤ 1:4. Additionally, reduction of anti-HLA class II antibody to mean fluorescence intensity (MFI) <3000 was achieved with both MP and CP. At 2 h of apheresis, CP reduced MFI by 2-3.5 fold and MP reduced MFI by 1.7-2.5 fold. Both demonstrated similar hemolytic and thrombotic profiles. CONCLUSIONS: In this in vitro plasmapheresis model of IT and anti-HLA antibody reduction, both MP and CP incorporated into the EC circuit can be used quickly and effectively to reduce circulating antibodies. While CP may have some greater efficiency, further study is necessary to verify this in vivo.

Hospitalizations for Respiratory Syncytial Virus and Vaccine Preventable Infections following Pediatric Heart Transplantation.

OBJECTIVE: To determine the risk factors for acquiring a respiratory syncytial virus (RSV) and vaccine-preventable infections (R/VPI) in pediatric heart transplant recipients and the associated morbidity and hospital resource use. STUDY DESIGN: Patients <18 years who underwent heart transplantation from September 2003 to December 2018 at hospitals using the Pediatric Health Information System database were identified. Their transplant hospitalization and subsequent hospitalizations for R/VPI through December 2018 were analyzed. Risk factors for R/VPI hospitalizations were evaluated using negative regression binomial models adjusted for demographic and clinical confounders. Total hospital costs were adjusted for 2018 US$. RESULTS: Of 3815 transplant recipients, 681 (17.9%) had an R/VPI hospitalization during 23 746 available person-years of follow-up. There were 984 R/VPIs diagnosed during 951 hospitalizations, and 440 (44.7%) occurred the first year after transplantation. The most common causes were RSV (n = 380; 38.6%), influenza (n = 265; 26.9%), and pneumococcus (n = 105; 10.7%). In adjusted analyses, there was an increased risk of R/VPI hospitalization in patients requiring mechanical circulatory support before transplantation, patients receiving induction with ≥2 immunosuppressive agents, and patients <2 years in the first year after transplantation. The median length of stay for an R/VPI hospitalization was 4 days (IQR, 2-8 days) with a median total cost of $11 081 (IQR, $6215-$24 322). CONCLUSIONS: Hospitalization for R/VPIs occurred frequently after heart transplantation and were associated with significant costs. Potential strategies to minimize R/VPI include expanding vaccine use through accelerated immunization schedules, further studies of use of palivizumab beyond 2 years of age, and immunogenicity monitoring after vaccination with re-immunization based on guidelines.

Epidemiology of Pediatric Hypertrophic Cardiomyopathy in a 10-Year Medicaid Cohort.

The epidemiologic data for pediatric hypertrophic cardiomyopathy (HCM) needs to be periodically updated as diagnostic techniques and management strategies improve. Herein, the incidence, prevalence, and mortality rates of pediatric HCM in a population-based treatment system are described. Patients aged ≤ 17 years and diagnosed with HCM on service visits over a 10-year period in one state Medicaid database (2007-2016) were analyzed. The cohort included 137 unique patients; 64.2% were male; 40.9% were African American; 42.3% were first diagnosed ≤ 24 months. The accrued 10-year prevalence rate for pediatric HCM was 1.2/1,000,000 and the annual incidence rate (CY 2010) was 1.3/100,000. Cardiac-related mortality was 2.9% in those who died cohort (N = 10); 70.0% of those who died were ≤ 13 months of age. Arrhythmia was diagnosed in 30.7% of the cohort, heart failure in 12.4%, and low birth weight in 8.8%. Inborn errors of metabolism were diagnosed in 8.0% of the cohort; malformation syndromes in 13.1%, and neuromuscular disorders in 2.9%; therefore, 75.9% were classified as idiopathic HCM. Our findings are somewhat higher than extant study estimates but update and augment them in representing a Southeast US statewide service system.

A case for genetic testing: Arrhythmogenic cardiomyopathy presenting as myocarditis.

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy associated with fibrofatty tissue replacement of the ventricular tissue. The disease can cause ventricular dysfunction and arrhythmias and can increase the risk of sudden cardiac death. This cardiomyopathy can have variable clinical presentations, especially in the pediatric and young adult populations. In this report, we describe the case of an 18-year-old female with myocarditis as the initial presentation of ACM. She presented following a resuscitated cardiac arrest due to ventricular arrhythmia. On arrival, myocardial edema and delayed gadolinium enhancement were present on cardiac magnetic resonance imaging, with no ventricular changes observed, making the diagnosis consistent with myocarditis. Genetic testing revealed a pathogenic mutation in the desmoplakin gene consistent with ACM. Given the unconventional initial presentation of this patient's disease, early consideration of genetic testing may be beneficial to aid in the early diagnosis and management of ACM in young patients.

Is there a future for the use of left ventricular assist devices in Duchenne muscular dystrophy?

Duchenne muscular dystrophy (DMD) is the most common form of childhood muscular dystrophy resulting in progressive muscle wasting and weakness. With advancements in respiratory care and the use of glucocorticoids, cardiomyopathy has surpassed respiratory compromise as the leading cause of morbidity and mortality in this patient population. As muscular dystrophy remains a relative contraindication to heart transplantation, end-stage heart failure management represents a major therapeutic challenge. Long-term left ventricular assist device (LVAD) therapy has emerged as a promising management strategy to improve the survival and quality of life in DMD cardiomyopathy. Preoperative planning, optimal patient selection, aggressive postoperative rehabilitation, and continued discussion of goals of care are critical considerations for the appropriate use of LVAD in DMD patients with cardiomyopathy.