Katheryn Gambetta

Background: Children with end‐stage dilated cardiomyopathy (DCM) usually undergo heart transplantation or a short‐term bridge with a ventricular assist device. Heartmate 3 (HM3) may represent an appealing longer‐term option, though pediatric data are limited. We analyzed two clinical registries and hypothesized that adolescents with DCM treated with either HM3 or transplant would present similar survival. Methods: The Pedimacs and Pediatric Heart Transplant Society registries were queried for DCM patients ages 10–18 years treated with HM3 or transplant, between 2017 and 2022. Mortality and adverse events were reported. Results: Ninety HM3 and 306 transplant patients were reported within the respective registries. There was a higher proportion of Black patients in the HM3 cohort (40% vs. 30% in the transplant cohort, p = 0.03). Twelve‐ and 36‐month survival rates were both 94.4% for HM3 patients and were 99.3% and 95.6% for transplant patients. In the HM3 group, there were 66 transplants (median time of 2.8 months), 3 late explants for recovery, and 3 early deaths. Conditional 1‐year survival for HM3 and transplant was 100% and 96.3%, respectively, at 3 years. In the HM3 group, bleeding, stroke, and device malfunction rates were low at 0.1 events per patient per year. Conclusions: Adolescents with DCM treated with either HM3 or transplant had excellent 3‐year outcomes, though many HM3 pediatric patients are transplanted early after device placement. Safely supporting this group of patients for an extended duration with HM3 has implications for delaying/avoiding transplantation, longer‐term patient survival, and donor organ availability.

Duchenne muscular dystrophy (DMD) is an X‐linked genetic neuromuscular disorder that is caused by a mutation in the dystrophin gene. The disease is characterized by progressive weakness of skeletal muscle, resulting in loss of ambulation and eventually respiratory insufficiency. Cardiac muscle is also involved, and cardiomyopathy is a prominent feature of DMD. The care of patients with DMD has changed in important ways over the past 15 years, with the use of chronic steroid therapy combined with noninvasive respiratory support such as continuous positive airway pressure for home use. More recently, therapies targeting specific genetic mutations in DMD have been approved, using gene‐skipping oligonucleotides, and many other novel therapies are being evaluated in clinical trials, including mini‐dystrophin genes delivered by viral vectors. In view of this new era in care and outcomes, it is appropriate to review the role of advanced cardiac therapies such as ventricular assist devices and heart transplantation in the care of this population. In September 2024, a group of healthcare professionals with expertise in DMD and heart failure convened to review this topic; the consensus opinion of this group (DMD Cardiac Care Consortium) is presented in this manuscript.

After pediatric heart transplant, commitment to lifelong immunosuppression is crucial to maintaining graft health. However, a review of the current literature surrounding adherence to immunosuppression in pediatric heart transplant patients is lacking. This systematic review aims to summarize the current landscape of adherence to immunosuppression in pediatric heart transplant patients. We conducted searches in PubMed MEDLINE, Embase, CENTRAL register of Controlled Trials (Wiley), and Scopus, from inception to March 2020. Studies were eligible if they outlined an aspect of adherence to immunosuppression and the measurement of adherence was performed with an objective or otherwise validated measure of adherence (e.g., drug levels, adherence questionnaires). The titles/abstracts of 880 articles were reviewed. After initial screening, 106 articles underwent full text review. As such, 14 articles were included in the final review. Baseline adherence estimates varied greatly, with most values between 40% and 70%. Nonadherence to immunosuppression is associated with worse outcomes (rejection, hospitalization, mortality), impaired quality of life, and mental health concerns in pediatric heart transplant patients. As nonadherence to immunosuppression is common and associated with worse outcomes, there is a need for further development and evaluation of interventions in this space.

Abnormal dystrophin production due to mutations in the dystrophin gene causes Duchenne Muscular Dystrophy (DMD). Cases demonstrate considerable genetic and disease progression variability. It is unclear if specific gene mutations are prognostic of outcomes in this population. We conducted a retrospective cohort study of DMD patients followed at 17 centers across the USA and Canada from 2005 to 2015 with goal of understanding the genetic variability of DMD and its impact on clinical outcomes. Cumulative incidence of clinically relevant outcomes was stratified by genetic mutation type, exon mutation location, and extent of exon deletion. Of 436 males with DMD, 324 (74.3%) underwent genetic testing. Deletions were the most common mutation type (256, 79%), followed by point mutations (45, 13.9%) and duplications (23, 7.1%). There were 131 combinations of mutations with most mutations located along exons 45 to 52. The number of exons deleted varied between 1 and 52 with a median of 3 exons deleted (IQR 1–6). Subjects with mutations starting at exon positions 40–54 had a later onset of arrhythmias occurring at median age 25 years (95% CI 18–∞), p = 0.01. Loss of ambulation occurred later at median age of 13 years (95% CI 12–15) in subjects with mutations that started between exons 55–79, p = 0.01. There was no association between mutation type or location and onset of cardiac dysfunction. We report the genetic variability in DMD and its association with timing of clinical outcomes. Genetic modifiers may explain some phenotypic variability.