Mariska S. Kemna

Dapagliflozin has been associated with euglycemic ketoacidosis in adults with diabetes contributing to poor outcomes when continued prior to surgery. It is unknown if preoperative use of dapagliflozin may lead to adverse events (AE) in nondiabetic children with advanced heart failure (HF) undergoing heart transplantation (HTx). We performed a single-center, matched case-control analysis of nondiabetic primary pediatric HTx recipients < 21 years-old who underwent HTx and followed through postoperative day (POD) 3. Cases who received dapagliflozin leading up to HTx (n = 22) were matched by age and cardiac diagnosis to two historical controls who did not receive dapagliflozin (n = 44). Median age at HTx was 13.8 years (range 0.36–20.7) and 48% were female. Cardiac diagnoses included cardiomyopathy (45%), Fontan failure (41%), and single ventricle status post stage I palliation (14%). Cases received median dapagliflozin dose of 0.17 mg/kg once daily; therapy was stopped one day prior to HTx. There were no significant differences in blood glucose nadirs, arterial blood gas indices including nadirs of pH, bicarbonate, or peaks of arterial blood lactic acid POD0-3. Vasopressor, inotrope, and insulin infusion usage were not different. No patients were treated for severe hypoglycemia, euglycemic ketoacidosis, or urinary tract infections. There were no deaths. Length of stay in ICU and time from HTx to hospital discharge did not differ between cohorts. Use of dapagliflozin in children with advanced HF until HTx is not associated with AE in the immediate postoperative period nor increased length of hospitalization post-HTx. Potential cardiovascular benefits of dapagliflozin in patients awaiting HTx should be prioritized.

Introduction: The prevalence of iron deficiency and anemia in the setting of modern‐day maintenance immunosuppression in pediatric heart transplant (HTx) recipients is unclear. The primary aim was to determine the prevalence of iron deficiency (serum ferritin < 30 ng/mL ± transferrin saturation < 20%) and anemia per World Health Organization diagnostic criteria and associated risk factors.Methods: Single‐center, cross‐sectional analysis of 200 consecutive pediatric HTx recipients (2 were independently associated with anemia. Ferritin < 30 ng/mL in isolation was not associated with anemia. Ferritin < 30 ng/mL may aid in detecting absolute iron deficiency while TSAT < 20% may be useful in identifying patients with functional iron deficiency ± anemia in pediatric HTx recipients.Conclusion: Iron deficiency and anemia are highly prevalent in pediatric HTx recipients. Future studies are needed to assess the impact of iron deficiency, whether with or without anemia, on clinical outcomes in pediatric HTx recipients.

Background: Pulmonary vein stenosis (PVS) is a rare pediatric condition associated with significant mortality and morbidity. PVS in patients following heart transplant (HT) has not yet been described.Methods: Patients who had clinically significant PVS following a heart transplant during the time period of April 1, 2013 to April 30, 2023, at Seattle Children's Hospital were identified. Clinically significant PVS was defined as an atretic vein or a vein with a gradient of ≥4 mmHg across at least one vein by echocardiogram or during cardiac catheterization. Patients who had a diagnosis of PVS prior to their transplant were excluded. A total of six patients were identified. We collected clinical data on these patients from their pre‐transplant course to their most recent status.Results: The median age at HT was 7.5 months (range 2–13 months). The median time from HT to diagnosis of PVS was 3.5 months (range 0.3–13 months). At the last follow‐up, the patients had had two to five pulmonary vein interventions, and there were no mortalities. The donor‐to‐recipient weight and total cardiac volume (TCV) ratios were less than 2.0 in five of six of the patients.Conclusions: PVS is a rare complication that is associated with patients who undergo HT during infancy. PVS develops soon after HT and screening should occur accordingly. Interestingly, high donor‐to‐recipient weight and TCV ratios are not necessarily associated with the development of PVS. Further work will need to be performed in order to determine the significance of PVS in post‐HT patients.

Therapies to support small infants in decompensated heart failure that are failing medical management are limited. We have used the hybrid approach, classically reserved for high-risk infants with single ventricle physiology, in patients with biventricular physiology with left ventricular failure. This approach secures systemic circulation, relieves left atrial hypertension, protects the pulmonary vasculature, and allows the right ventricle to support cardiac output. This approach can be used as a bridge to transplantation in select individuals. Infants without single ventricle congenital heart disease who were treated with the hybrid approach between 2008 and 2021 were included in analysis. Eight patients were identified. At the time of hybrid procedure, the median weight was 3.2 kg (range 2.4–3.6 kg) and the median age was 18 days (range 1–153 days). Seventy five percent were mechanically ventilated and 88% were on inotropic support. The median duration from hybrid procedure to transplant was 63 days (range 4–116 days). All patients experienced a good outcome (delisted for improvement or transplanted). The hybrid procedure is an appropriate therapeutic bridge to transplantation in a carefully selected subset of critically ill infants without single ventricle congenital heart disease in whom alternate therapies may confer increased risk for morbidity and mortality.

Introduction: Pharmacokinetics of mycophenolic acid (MPA) display substantial interpatient variability, with up to 10‐fold difference of exposure in individual patients under a fixed‐dose regimen. MPA trough level (C0) monitoring is common in clinical practice but has not proven sufficiently informative in predicting MPA exposure or patient outcomes, especially in children. No limited sampling strategies (LSSs) have been generated from pediatric heart transplant (HTx) recipients to estimate MPA AUC.Methods: Single‐center, observational analysis of 135 de novo pediatric HTx recipients ≤21 years old who underwent MPA AUC between 2011 and 2021.Results: Median age was 4 years (IQR .6–12.1). Median time from transplant to MPA AUC sampling was 15 days (IQR 11–19). MMF doses (mg or mg/day) had low, negative Pearson correlation coefficients (r) while doses adjusted for weight or body surface area had low correlation with Trapezoidal MPA AUC_0–24 h (r = .3 and .383, respectively). MPA C0 had weak association (r = .451) with Trapezoidal MPA AUC_0–24 h. LSS with two pharmacokinetic sampling time points at 90 (C₃) and 360 (C₅) min after MMF administration (estimated AUC_0–24 h = 32.82 + 4.12 × C₃ + 11.53 × C₅) showed strong correlation with Trapezoidal MPA AUC_0–24 h (r = .87).Conclusion: MMF at fixed or weight‐adjusted doses, as well as MPA trough levels, correlate poorly with MPA AUC_0–24 h. We developed novel LSSs to estimate Trapezoidal MPA AUC from a large cohort of pediatric HTx recipients. Validation of our LSSs should be completed in a separate cohort of pediatric HTx recipients.

Background: Literature is limited comparing adverse effects (AEs) of the proliferation signal inhibitors (PSIs) sirolimus (SRL) and everolimus (EVL) in pediatric heart transplant (HTx) recipients.Methods: Single‐center, observational cohort analysis assessing first use of SRL or EVL in pediatric HTx recipients p < .05). There were no differences in hematological indices or rates of aphthous ulcers, effusions, or infections between cohorts. Incidence of proteinuria was not significantly different among those screened within cohorts. Of those included in our analysis, one patient in SRL cohort (2.9%) and two in EVL cohort (3.8%) had PSI withdrawn due to AE.Conclusion: Low‐dose PSIs in calcineurin inhibitor minimization regimens appear well‐tolerated with low withdrawal rate secondary to AE in pediatric HTx recipients. While incidence of most AE was similar between PSI, our results suggest EVL may be associated with less favorable metabolic impact than SRL in this population.