The Fontan immunophenotype and post-transplant outcomes in children: A multi-institutional study.

BACKGROUND: Patients after Fontan palliation represent a growing pediatric population requiring heart transplant (HTx) and often have lymphopenia (L) and/or hypogammaglobinemia that may be exacerbated by protein-losing enteropathy (PLE, P). The post-HTx effects of this altered immune phenotype are not well studied. METHODS: In this study of the Pediatric Heart Transplant Society Registry, 106 Fontan patients who underwent HTx between 2005 and 2018 were analyzed. The impact of lymphopenia and PLE on graft survival, infection, rejection, and malignancy was analyzed at 1 and 5 years post-HTx. RESULTS: The following combinations of lymphopenia and PLE were noted: +L+P, n = 37; +L-P, n = 23; -L+P, n = 10; and -L-P, n = 36. Graft survival between the groups was similar within the first year after transplant (+L+P: 86%, +L-P: 86%, -L+P: 87%, -L-P: 89%, p = .9). Freedom from first infection post-HTx was greatest among -L-P patients compared to patients with either PLE, lymphopenia, or both; with a 22.1% infection incidence in the -L-P group and 41.4% in all others. These patients had a significantly lower infection rate in the first year after HTx (+L+P: 1.03, +L-P: 1, -L+P: 1.3, -L-P: 0.3 infections/year, p < .001) and were similar to a non-single ventricle CHD control group (0.4 infections/year). Neither freedom from rejection nor freedom from malignancy 1 and 5 years post-HTx, differed among the groups. CONCLUSIONS: Fontan patients with altered immunophenotype, with lymphopenia and/or PLE, are at increased risk of infection post-HTx, although have similar early survival and freedom from rejection and malignancy. These data may encourage alternative immunosuppression strategies and enhanced monitoring for this growing subset of patients.

Immune Response to SARS-CoV-2 Vaccine among Heart Transplant Recipients: A Systematic Review.

Background: Heart transplant (HTX) recipients are at a significantly higher risk of adverse clinical outcomes, due to chronic immunosuppression and co-existence of other chronic conditions, when contracting the SARS-CoV-2 infection. Although vaccination against SARS-CoV-2 is currently the most promising measure for the prevention of severe Coronavirus Disease 2019 (COVID-19) among solid organ transplant recipients, the extent of immune response and its protective efficacy among patients receiving HTX has not been sufficiently studied. Methods: We performed a systematic review of the literature by inquiring PubMed/Medline to identify original studies among HTX recipients, who had received at least one dose of the SARS-CoV-2 vaccine. Data on the measured humoral or cellular immune response was collected from all the eligible studies. Factors associated with a poor immune response were further investigated within these studies. Results: A total of 12 studies comprising 563 HTX recipients were included. The average age of the study participants was 60.8 years. Sixty four percent of the study population were male. Ninety percent of the patients had received an mRNA vaccine (Pfizer/ BNT162b2 or Moderna/mRNA-1273). A positive immune response to SARS-CoV-2 vaccine was variably reported in 0% to 100% of the patients. Older age (> 65 years), vaccine dose (first, second, or third), time since HTX to the first dose of the vaccine, the time interval between the latest dose of the vaccine and measurement of the immune response, and the type of immunosuppressive regimen were all indicated as potential determinants of a robust immune response to the SARS-CoV-2 vaccination. Conclusion: HTX recipients demonstrate a weaker immune response to the vaccination against SARS-CoV-2 compared to the general population. Older age, anti-metabolite agents such as mycophenolate mofetil, and vaccination during the first year following the HTX have been indicated as potential determinants of a poor immune response.

Rapid Growth of Left Atrial Thrombus in a Pediatric Heart Transplant Recipient.

We report on a 10-year-old female patient who rapidly developed a left atrial (LA) mass 2 months after orthotopic heart transplant. Nine days prior to detection of the mass, she received high-dose corticosteroids for acute cellular rejection (grade 2). Despite negative echocardiogram 5 days prior to detection, a large echogenic mass was noted in the LA (18 x 12 x 24 mm); it was surgically resected after unsuccessful anticoagulation treatment. Pathogenesis of this LA thrombus remains uncertain, but immunosuppression, acute rejection, and high-dose steroid therapy may have contributed. Surgical thrombectomy is a safe and effective treatment option for LA thrombus.