Does asymptomatic recurrent diffuse capillary C4d complement deposition impair cardiac allograft function?

Clin Transplant. 2016 Oct;30(10):1314-1323. doi: 10.1111/ctr.12824. Epub 2016 Sep 24.

Abstract

Background: The aim of this study was to evaluate whether asymptomatic recurrent (≥2) antibody-mediated rejection (pAMR 1+), defined as diffuse capillary C4d immunostaining (rAMR) on endomyocardial biopsies (EMBs), during the first year after heart transplantation impairs left ventricular (LV) function.

Methods: Fifty-four consecutive heart transplant patients who survived well (New York Heart Association ≤2 and EF≥55%) the first month after transplantation were enrolled and prospectively underwent 490 echocardiographies and EMB. Asymptomatic rAMR without histopathologic findings was evaluated as a risk factor for deterioration of graft function. Primary endpoint, assessed 1 year after transplantation, was development of LV dysfunction and/or adverse remodeling according to pre-specified echo parameters.

Results: During the first year from transplantation, rAMR occurred in five patients. Recurrent AMR was associated with a significant higher risk to develop LV concentric hypertrophy (OR 3.6, 95% CI: 1.8-7.0, P=.02) or reduced lateral S' peak velocity (OR 2.3, 95% CI: 1.5-3.6, P=.03). Patients with rAMR showed significative adverse graft remodeling (ΔLV end-diastolic volume: +16±12.3 vs -0.2±14.4 mL; P=.02) and deterioration of graft function (Δlateral S' peak velocity: -3.3±3 vs -0.4±2.9 cm/s; P=.03).

Conclusions: Recurrent asymptomatic diffuse capillary C4d immunostaining may play a role in the early development of cardiac allograft adverse remodeling and dysfunction.

Keywords: C4d complement deposition; antibody-mediated cardiac allograft rejection; cardiac allograft vasculopathy; cardiac remodeling; echocardiography; endomyocardial biopsy; heart transplant; immunochemistry; tissue Doppler imaging.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Asymptomatic Diseases
  • Biomarkers / metabolism
  • Biopsy
  • Capillaries / immunology*
  • Capillaries / pathology
  • Complement C4b / metabolism*
  • Echocardiography, Doppler
  • Female
  • Follow-Up Studies
  • Graft Rejection / complications*
  • Graft Rejection / diagnosis*
  • Graft Rejection / immunology
  • Graft Rejection / pathology
  • Heart Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Myocardium / immunology
  • Myocardium / pathology
  • Outcome Assessment, Health Care
  • Peptide Fragments / metabolism*
  • Postoperative Complications / diagnostic imaging
  • Postoperative Complications / etiology*
  • Prospective Studies
  • Recurrence
  • Transplantation, Homologous
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / etiology*

Substances

  • Biomarkers
  • Peptide Fragments
  • Complement C4b
  • complement C4d