Atypical infiltrates on endomyocardial biopsy are associated with adverse outcomes in pediatric heart transplantation

Kyle D Hope; Shaine A Morris; Debra L Kearney; Kriti Puri; Swati Choudhry; Joseph A Spinner; Hari P Tunuguntla; Jack F Price; William J Dreyer; Sarah K Nicholas; Susan W Denfield

doi:10.1016/j.healun.2023.06.007

Atypical infiltrates on endomyocardial biopsy are associated with adverse outcomes in pediatric heart transplantation

J Heart Lung Transplant. 2023 Dec;42(12):1743-1752. doi: 10.1016/j.healun.2023.06.007. Epub 2023 Jul 18.

Authors

Affiliations

¹ Lillie Frank Abercrombie Division of Pediatric Cardiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas. Electronic address: kyle.hope@bcm.edu.
² Lillie Frank Abercrombie Division of Pediatric Cardiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
³ Division of Pediatric Cardiac & Surgical Pathology, Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
⁴ Lillie Frank Abercrombie Division of Pediatric Cardiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas; Division of Pediatric Critical Care Medicine, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
⁵ Division of Pediatric Allergy and Immunology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
⁶ Division of Pediatric Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.

PMID: 37473824
DOI: 10.1016/j.healun.2023.06.007

Abstract

Background: The significance of atypical infiltrates (eosinophils or plasma cells) on endomyocardial biopsy (EMB) after pediatric heart transplant (HTx) is not known. We hypothesized that atypical infiltrates are associated with worse post-HTx outcomes.

Methods: We performed a retrospective cohort study of consecutive patients <21 years old who underwent primary HTx between 2013 and 2017. Multiorgan transplants were excluded. The presence of atypical infiltrates and burden of atypical infiltrates (rare vs predominant) on EMB were recorded. Primary outcome was a composite of cardiac allograft vasculopathy, graft failure (relisting or retransplant), or death. Presence of atypical infiltrates was evaluated: (1) overall using Cox regression with time-dependent covariates and (2) if present by 1 year post-HTx using Kaplan-Meier analysis.

Results: Atypical infiltrates were present in 24 out of 95 patients (25%) and were associated with a higher likelihood of reaching the composite outcome (hazard ratio (HR) 6.22, 95% confidence interval (CI) 2.60-14.89, p < 0.0001). This persisted when controlling for rejection in multivariable analysis. There was also a greater risk of the composite outcome if ≥2 nonconsecutive EMBs had atypical infiltrates (HR 11.80, 95%CI 3.17-43.84, p = 0.0002) or if atypical infiltrates were the predominant feature on EMB (HR 30.58, 95%CI 9.34-100.06, p < 0.0001). Patients with atypical infiltrates by 1-year post-HTx had a 5-year freedom from the composite outcome of 48%, compared to 90% if no atypical infiltrates had been present by this timepoint (log rank p = 0.002).

Conclusions: The presence of atypical infiltrates on EMB is associated with significantly worse outcomes in children following HTx. These patients require closer follow-up to assess for developing graft dysfunction.

Keywords: endomyocardial biopsy; eosinophils; infiltrates; outcomes; pediatric heart transplant; plasma cells.

MeSH terms

Adult
Biopsy
Cardiac Catheterization
Child
Graft Rejection / epidemiology
Graft Rejection / pathology
Heart Transplantation* / adverse effects
Humans
Retrospective Studies
Young Adult