title: Does asymptomatic recurrent diffuse capillary C4d complement deposition impair cardiac allograft function?
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  Recurrent asymptomatic diffuse capillary C4d immunostaining may play a role in the early development of cardiac allograft adverse remodeling and dysfunction.
authors.affiliation: Division of Cardiology, Internal Medicine Department, Città della Salute e della Scienza and University of Torino, Torino, Italy. simone.frea@libero.it.
authors.forename: Simone
authors.initials: S
authors.lastname: Frea
authors.affiliation: Division of Cardiology, Internal Medicine Department, Città della Salute e della Scienza and University of Torino, Torino, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Iacovino
authors.affiliation: Division of Cardiology, Internal Medicine Department, Città della Salute e della Scienza and University of Torino, Torino, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Botta
authors.affiliation: Division of Cardiology, Internal Medicine Department, Città della Salute e della Scienza and University of Torino, Torino, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: De Filippi
authors.affiliation: Department of Biomedicine and Human Oncology, University of Torino, Torino, Italy.
authors.forename: Gianna
authors.initials: G
authors.lastname: Mazzucco
authors.affiliation: Division of Cardiology, Internal Medicine Department, Città della Salute e della Scienza and University of Torino, Torino, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pidello
authors.affiliation: Division of Cardiology, Internal Medicine Department, Città della Salute e della Scienza and University of Torino, Torino, Italy.
authors.forename: CarloAlberto
authors.initials: C
authors.lastname: Biolè
authors.affiliation: Division of Cardiology, Internal Medicine Department, Città della Salute e della Scienza and University of Torino, Torino, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Bergerone
authors.affiliation: Division of Cardiac Surgery, Cardiovascular and Thoracic Department, Città della Salute e della Scienza and University of Torino, Torino, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Boffini
authors.affiliation: Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Praticò Barbato
authors.affiliation: Division of Cardiology, Internal Medicine Department, Città della Salute e della Scienza and University of Torino, Torino, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Morello
authors.affiliation: Division of Cardiac Surgery, Cardiovascular and Thoracic Department, Città della Salute e della Scienza and University of Torino, Torino, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Rinaldi
authors.affiliation: Division of Cardiology, Internal Medicine Department, Città della Salute e della Scienza and University of Torino, Torino, Italy.
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Gaita
mesh_terms: D000328:Adult; D000368:Aged; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002196:Capillaries / Q000276:immunology* / Q000473:pathology; D015935:Complement C4b / Q000378:metabolism*; D015150:Echocardiography, Doppler; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000150:complications* / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D017063:Outcome Assessment, Health Care; D010446:Peptide Fragments / Q000378:metabolism*; D011183:Postoperative Complications / Q000000981:diagnostic imaging / Q000209:etiology*; D011446:Prospective Studies; D012008:Recurrence; D014184:Transplantation, Homologous; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d
keywords: C4d complement deposition; antibody-mediated cardiac allograft rejection; cardiac allograft vasculopathy; cardiac remodeling; echocardiography; endomyocardial biopsy; heart transplant; immunochemistry; tissue Doppler imaging