Late graft dysfunction after pediatric heart transplantation is associated with fibrosis and microvasculopathy by automated, digital whole-slide analysis.
J Heart Lung Transplant
; 36(12): 1336-1343, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-29055602
ABSTRACT
BACKGROUND:
Histopathologic features of late graft dysfunction (LGD) in endomyocardial biopsies (EMBs) after pediatric heart transplantation (HT) have been incompletely described and rarely quantified. We employed automated, morphometric analysis of whole-slide EMB images to objectively quantify fibrosis and microvasculopathy after pediatric HT.METHODS:
Nine recipients with clinical LGD were matched with controls on age, listing diagnosis, crossmatch and time since HT. Fibrosis was quantified as percent tissue area with fibrosis and capillary density as capillaries per unit area, number of capillary "neighbors" within 30 µm of each myocyte and myocyte-to-nearest-capillary diffusion distance. Clinical data, including all EMB reports, were also reviewed.RESULTS:
The groups were well matched for age at HT (median 4.0 vs 3.1 years), listing diagnosis (50% congenital heart disease for each), positive crossmatch (11% each) and days post-HT (2,628 vs 2,894, p = 0.69). Despite a similar number of previous EMBs (median 23 each, p = 0.43), areas occupied by fibrosis were greater in LGD cases (44.5% vs 23.2%, p = 0.012). Capillary number/area data were not statistically different between LGD cases and controls (378/mm2 vs 559/mm2, p = 0.57), but LGD cases more commonly had zero capillary neighbors (35% vs 20%, p = 0.02) and greater myocyte-to-nearest-capillary distances (27.1 µm vs 18.7 µm, p = 0.005). Cumulative rejection history correlated with fibrosis (r = 0.49, p = 0.039) and myocyte-to-nearest-capillary distance (r = 0.5, p = 0.036).CONCLUSIONS:
LGD after pediatric HT is associated with previous rejection and characterized histologically by fibrosis and microvasculopathy, which are not readily appreciated by traditional semi-quantitative EMB analysis. Software-assisted EMB analysis may enable greater pathophysiologic understanding of LGD and identification of targets for future study and intervention.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Automação
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Transplante de Coração
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Vasos Coronários
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Função Retardada do Enxerto
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Cardiopatias Congênitas
/
Miocárdio
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Child
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Child, preschool
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Female
/
Humans
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Infant
/
Male
Idioma:
En
Revista:
J Heart Lung Transplant
Assunto da revista:
CARDIOLOGIA
/
TRANSPLANTE
Ano de publicação:
2017
Tipo de documento:
Article