Relationship between prolonged QTc interval, cardiac allograft dysfunction and elevated molecular gene expression profiling test score after heart transplantation

Abstract

Acute cellular cardiac allograft rejection after heart transplantation (HTx) is diagnosed histologically using endomyocardial biopsy (EMB), which is associated with limitations. 1 Marboe C.C. Billingham M. Eisen H. et al. Nodular endocardial infiltrates (Quilty lesions) cause significant variability in diagnosis of ISHLT Grade 2 and 3A rejection in cardiac allograft recipients. J Heart Lung Transplant. 2005; 24: S219-S226 Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar Using gene expression profiling (GEP) of peripheral blood mononuclear cells (PBMCs), a molecular classifier was developed and validated to rule out International Society of Heart and Lung Transplantation (ISHLT) moderate/severe (Grade ≥3A/2R) rejection, 2 Deng M.C. Eisen H.J. Mehra M.R. et al. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant. 2006; 6: 150-160 Crossref PubMed Scopus (414) Google Scholar with a high negative predictive value of 99.6%. The corrected QT (QTc) interval has been described as a sensitive and specific tool to predict acute cellular cardiac allograft rejection. 3 Richartz B.M. Radovancevic B. Bologna M.T. et al. Usefulness of the QTc interval in predicting acute allograft rejection. Thorac Cardiovasc Surg. 1998; 46: 217-221 Crossref PubMed Scopus (18) Google Scholar We have recently shown that the GEP score correlates with the QTc interval during quiescence. 4 Cadeiras M. Shahzad K. John M.M. et al. Relationship between a validated molecular cardiac transplant rejection classifier and routine organ function parameters. Clin Transplant. 2009; (Aug 27. [Epub ahead of print]) PubMed Google Scholar In the present pilot study we hypothesized that both increased QTc interval and elevated GEP score are associated with allograft dysfunction, as defined by echocardiographic (TTE) criteria.