Key result
Biopsy molecular phenotype correlates with Quilty lesions, microcirculation lesions, and decreased LVEF, not histologic rejection.
Why the study?
The ISHLT consensus criteria for interpreting heart transplant biopsy rejection are arbitrarily defined and may not reflect the molecular phenotype or clinical relevance.
Does molecular phenotyping of heart transplant biopsies correlate better with clinical variables and tissue injury than standard ISHLT histologic diagnosis?
Observational (n=45)
Does molecular phenotyping of heart transplant biopsies correlate better with clinical variables and tissue injury than standard ISHLT histologic diagnosis?
Molecular phenotyping of heart transplant biopsies correlates with clinical dysfunction and tissue injury better than standard ISHLT histologic criteria, suggesting a need to revise current diagnostic systems.
Answers are grounded in this paper and cite their sources.
Questions histologic rejection diagnosis as the standard; hypothesis-generating for molecular phenotyping in transplant monitoring.
Histopathology of endomyocardial biopsies (EMB) is the standard rejection surveillance for heart transplants. However, ISHLT consensus criteria for interpreting biopsies are arbitrarily defined. Gene expression offers an independent re-evaluation of existing diagnostic systems. We performed histologic and microarray analysis on 105 EMB from 45 heart allograft recipients. Histologic lesions, diagnosis and transcripts were compared to one another, time posttransplantation, indication for biopsy and left ventricular ejection fraction (LVEF). Histologic lesions presented in two groups: myocyte-interstitial and microcirculation lesions. Expression of transcript sets reflecting T cell and macrophage infiltration, and γ-interferon effects correlated strongly with each other and with transcripts indicating tissue/myocardium injury. This molecular phenotype correlated with Quilty (p < 0.005), microcirculation lesions (p < 0.05) and decreased LVEF (p < 0.007), but not with the histologic diagnosis of rejection. In multivariate analysis, LVEF was associated (p < 0.03) with γ-interferon inducible transcripts, time posttransplantation, ischemic injury and clinically indicated biopsies, but not the diagnosis of rejection. The results indicate that (a) the current ISHLT system for diagnosing rejection does not reflect the molecular phenotype in EMB and lacks clinical relevance; (b) the interpretation of Quilty lesions has to be revisited; (c) the assessment of molecules in heart biopsy can guide improvements of current diagnostics.
No takes yet. Share an insight, caveat, or question.
Mengel et al. (2010) conducted an observational in Heart transplant (n=45). Molecular phenotype (microarray analysis) vs. Histologic diagnosis (ISHLT criteria) was evaluated on Correlation of molecular phenotype with clinical and histopathological variables (p=<0.005). Molecular phenotype of heart transplant biopsies correlated with Quilty lesions, microcirculation lesions, and decreased LVEF, but not with histologic rejection diagnosis.
Synapse has enriched 10 related papers. Consider them for comparative context: