BACKGROUND: Antibody-mediated rejection (AMR) of cardiac allografts is associated with reduced long-term graft survival, but not every patient with AMR develops premature graft failure. The tissue level mechanisms leading to graft failure in some patients with antibody-mediated rejection are poorly characterized. METHODS: We assessed changes in myocardial microvessel density (number of capillaries per unit area) in endomyocardial biopsies over time using whole-slide microscopic imaging of CD34-stained slides and computer-assisted image analysis. Changes were compared among eight heart transplant recipients with multiple episodes of pathologic AMR who died from cardiovascular causes, eight age- and gender-matched patients with pathologic AMR who were still alive at a similar follow-up interval, and six matched controls without AMR or cellular rejection. RESULTS: Microvessel density decreased in the last biopsies (mean 6.52 years post-transplant) from patients with pathologic AMR and cardiovascular mortality compared to their biopsies at 6 and 12 months post-transplant [respectively, -22% (P=.02) and -25% (P=.02)]. A similar decrease was not seen for the other groups. CONCLUSIONS: Significantly reduced myocardial microvessel density does occur in a subset of patients with pathologic AMR who have a worse outcome. These data provide insights into the interplay between AMR, microvascular injury, and clinical outcomes.
BACKGROUND: Antibody-mediated rejection (AMR) of cardiac allografts is associated with reduced long-term graft survival, but not every patient with AMR develops premature graft failure. The tissue level mechanisms leading to graft failure in some patients with antibody-mediated rejection are poorly characterized. METHODS: We assessed changes in myocardial microvessel density (number of capillaries per unit area) in endomyocardial biopsies over time using whole-slide microscopic imaging of CD34-stained slides and computer-assisted image analysis. Changes were compared among eight heart transplant recipients with multiple episodes of pathologic AMR who died from cardiovascular causes, eight age- and gender-matched patients with pathologic AMR who were still alive at a similar follow-up interval, and six matched controls without AMR or cellular rejection. RESULTS: Microvessel density decreased in the last biopsies (mean 6.52 years post-transplant) from patients with pathologic AMR and cardiovascular mortality compared to their biopsies at 6 and 12 months post-transplant [respectively, -22% (P=.02) and -25% (P=.02)]. A similar decrease was not seen for the other groups. CONCLUSIONS: Significantly reduced myocardial microvessel density does occur in a subset of patients with pathologic AMR who have a worse outcome. These data provide insights into the interplay between AMR, microvascular injury, and clinical outcomes.
Authors: X Jiang; T T Nguyen; W Tian; Y K Sung; K Yuan; J Qian; J Rajadas; J-M Sallenave; N P Nickel; V de Jesus Perez; M Rabinovitch; M R Nicolls Journal: Am J Transplant Date: 2015-02-27 Impact factor: 8.086
Authors: Eliot G Peyster; Andrew Janowczyk; Abigail Swamidoss; Samhith Kethireddy; Michael D Feldman; Kenneth B Margulies Journal: Circulation Date: 2022-04-11 Impact factor: 39.918
Authors: P Bruneval; A Angelini; D Miller; L Potena; A Loupy; A Zeevi; E F Reed; D Dragun; N Reinsmoen; R N Smith; L West; S Tebutt; T Thum; M Haas; M Mengel; P Revelo; M Fedrigo; J P Duong Van Huyen; G J Berry Journal: Am J Transplant Date: 2016-12-12 Impact factor: 8.086