Prevalence of iron deficiency and anemia in pediatric heart transplant recipients.

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 (<21 years old) from 2005 to 2021. Data were collected at 1-year post-HTx at the time of annual protocol biopsy. RESULTS: Median age at transplant was 3 years (IQR .5-12.2). The median ferritin level was 32 ng/mL with 46% having ferritin < 30 ng/mL. Median transferrin saturation (TSAT) was 22% with 47% having TSAT < 20%. Median hemoglobin was 11 g/dL with 54% having anemia. Multivariable analysis revealed lower absolute lymphocyte count, TSAT < 20%, and estimated glomerular filtration rate <75 mL/min/1.73 m2 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.

Dapagliflozin Use in Children with Advanced Heart Failure Undergoing Heart Transplantation: A Matched Case-Control Study.

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.

Analysis of Platelet Function Testing in Children Receiving Aspirin for Antiplatelet Effects.

Aspirin (ASA) remains the most common antiplatelet agent used in children. VerifyNow Aspirin Test® (VN) assesses platelet response to ASA, with therapeutic effect defined by the manufacturer as ≤ 549 aspirin reaction units (ARU). Single-center, observational, analysis of 195 children (< 18 years-old) who underwent first VN between 2015 and 2020. Primary outcome was proportion of patients with ASA biochemical resistance (> 549 ARU). Secondary outcomes included incidence of new clinical thrombotic and bleeding events during ≤ 6 months from VN in those who received ASA monotherapy (n = 113). Median age was 1.8 years. Common indications for ASA included cardiac anomalies or dysfunction (74.8%) and ischemic stroke (22.6%). Median ASA dose before VN was 4.6 mg/kg/day. Mean VN was 471 ARU. ASA biochemical resistance was detected in 14.4% (n = 28). Of 113 patients receiving ASA monotherapy, 14 (12.4%) had a thrombotic event and 2 (1.8%) had a bleeding event. Mean VN was significantly higher at initial testing in patients experiencing thrombotic event compared to those without thrombosis (516 vs 465 ARU, [95% CI: 9.8, 92.2], p = 0.02). Multivariable analysis identified initial VN ASA result ≥ 500 ARU at initial testing as the only significant independent risk factor for thrombosis (p < 0.01). VN testing identifies ASA biochemical resistance in 14.4% of children. VN ASA ≥ 500 ARU rather than ≥ 550 ARU at initial testing was independently associated with increased odds of thrombosis. Designated cut-off of 550 ARU for detecting platelet dysfunction by ASA may need reconsideration in children.

Mycophenolic acid therapeutic drug monitoring using area under the curve in pediatric heart transplant recipients.

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 AUC0-24 h (r = .3 and .383, respectively). MPA C0 had weak association (r = .451) with Trapezoidal MPA AUC0-24 h . LSS with two pharmacokinetic sampling time points at 90 (C3 ) and 360 (C5 ) min after MMF administration (estimated AUC0-24 h  = 32.82 + 4.12 × C3  + 11.53 × C5 ) showed strong correlation with Trapezoidal MPA AUC0-24 h (r = .87). CONCLUSION: MMF at fixed or weight-adjusted doses, as well as MPA trough levels, correlate poorly with MPA AUC0-24 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.