Histopathology, mRNA expression profile, and donor-derived cell-free DNA for assessment of rejection in pediatric heart transplantation.

BACKGROUND: The relationship between histopathologic and molecular ("MMDx"®) assessments of endomyocardial biopsy (EMB) and serum donor-derived cell-free DNA (ddcfDNA) in acute rejection (AR) assessment following pediatric heart transplantation (HT) is unknown. METHODS: EMB sent for MMDx and histopathology from November 2021 to September 2022 were reviewed. MMDx and histopathology results were compared. DdcfDNA obtained ≤1 week prior to EMB were compared with histopathology and MMDx results. The discrimination of ddcfDNA for AR was assessed using receiver-operating curves. FINDINGS: In this study, 177 EMBs were obtained for histopathology and MMDx, 101 had time-matched ddcfDNA values. MMDx and Histopathology displayed moderate agreement for T-cell-mediated rejection (TCMR, Kappa = 0.52, p < .001) and antibody-mediated rejection (ABMR, Kappa = 0.41, p < .001). Discordant results occurred in 24% of cases, most often with ABMR. Compared with no AR, ddcfDNA values were elevated in cases of AR diagnosed by both histopathology and MMDx (p < .01 for all). Additionally, ddcfDNA values were elevated in injury patterns on MMDx, even when AR was not present (p = .01). DdcfDNA displayed excellent discrimination (AUC 0.83) for AR by MMDx and/or histopathology. Using a threshold of ≥0.135%, ddcfDNA had a sensitivity of 90%, specificity of 63%, PPV of 52%, and NPV of 94%. CONCLUSIONS: Histopathology and MMDx displayed moderate agreement in diagnosing AR following pediatric HT, with most discrepancies noted in the presence of ABMR. DdcfDNA is elevated with AR, with excellent discrimination and high NPV particularly when utilizing MMDx. A combination of all three tests may be necessary in some cases.

Interventions on residual lesions in patients with heterotaxy syndrome following orthotropic heart transplantation: A single-center experience.

BACKGROUND: Heterotaxy syndrome (HS) is a defect in lateralization which often results in complex intra and extracardiac abnormalities. Orthotropic heart transplantation (OHT) in HS involves intricate and individualized modifications to surgical technique. Post-OHT outcomes are worse in patients with HS, however, the impact of post-OHT residual lesions has not yet been characterized. METHODS: Patients with HS who underwent OHT at Ann & Robert H. Lurie Children's Hospital of Chicago between January 2012 and June 2023 were identified. Patients were excluded if follow-up data was not available due to follow up at a different institution of early mortality. Pre-OHT clinical data, surgical data, and post-OHT surgical and catheterization data were collected. RESULTS: Two early mortalities were excluded from analysis, leaving 15 patients in the study cohort. Median age at OHT was 3.7 years (range: 0.7-15.4). Nine out of 15 patients were diagnosed with residual lesions requiring intervention at a median of 188 days post transplantation. All interventions on residual lesions occurred via catheterization. Overall mortality rate was 27% (4/15) with all deaths occurring in patients with residual lesions (4/9 patients, 44%). 83% (10/12) of lesions were diagnosed via catheterization, and 83% (10/12) of lesions of occurred in the first year after transplant. CONCLUSIONS: Patients with HS are at high risk for residual lesions after OHT, which may contribute to increased mortality. Comprehensive invasive diagnostics were required to diagnose residual lesions, which were all addressed percutaneously.

Differences in outcomes between surgical pericardial window and pericardiocentesis in children with postpericardiotomy syndrome.

Children with postpericardiotomy syndrome may develop hemodynamically significant pericardial effusions warranting drainage by surgical pericardial window or pericardiocentesis. The optimal approach is unknown. We performed a retrospective observational study at two pediatric cardiac centers. We included 42 children aged <18 years who developed postpericardiotomy syndrome following cardiac surgery between 2014 and 2021. Thirty-two patients underwent pericardial window and 10 underwent pericardiocentesis. Patients in the pericardial window group presented with postpericardiotomy syndrome sooner than those who underwent pericardiocentesis (median 7.5 days vs. 14.5 days, P = 0.03) and tended to undergo earlier intervention (median 8 days vs. 16 days, P = 0.16). No patient required subsequent drainage. There were no differences between groups in days of pericardial tube duration (median 4 days), complications, and subsequent days of intensive care or hospitalization. For children with postpericardiotomy syndrome with a pericardial effusion warranting drainage, these data suggest that pericardial window and pericardiocentesis have similar efficacy, safety, and resource utilization.

Left Atrial Hypertension and Respiratory Failure Requiring Venoarterial ECMO After Transcatheter Pulmonary Valve Replacement.

A 33-year-old woman with aortic valve stenosis status-post Ross at age 6 years developed symptomatic right heart failure from right ventricle to pulmonary artery conduit stenosis. Conduit rehabilitation and transcatheter pulmonary valve replacement resulted in acute left atrial hypertension and respiratory failure requiring venoarterial extracorporeal membrane oxygenation and atrial septal defect creation as a bridge to recovery.