Association of Viral Genome with Graft Loss in Children after Cardiac Transplantation
Girish S. Shirali, M.D., Jiyuan Ni, M.D., Richard E. Chinnock, M.D., Joyce K. Johnston, R.N., B.S., Geoffrey L. Rosenthal, M.D., Ph.D., Neil E. Bowles, Ph.D., and Jeffrey A. Towbin, M.D.
Background The survival of recipients of cardiac allograftsis limited by rejection and coronary vasculopathy. The purposeof this study in children who had received heart transplantswas to evaluate the cardiac allografts for myocardial viralinfections and to determine whether the presence of viral genomein the myocardium correlates with rejection, coronary vasculopathy,or graft loss.
Methods We enrolled heart-transplant recipients 1 day to 18years old who were undergoing evaluation for possible rejectionand coronary vasculopathy. Endomyocardial-biopsy specimens wereevaluated for evidence of rejection with the use of standardcriteria and were analyzed for the presence of virus by thepolymerase chain reaction (PCR).
Results PCR analyses were performed on 553 consecutive biopsysamples from 149 transplant recipients. Viral genome was amplifiedfrom 48 samples (8.7 percent) from 34 patients (23 percent);adenovirus was found in 30 samples, enterovirus in 9 samples,parvovirus in 5 samples, cytomegalovirus in 2 samples, herpessimplex virus in 1 sample, and EpsteinBarr virus in 1sample. In 29 of the 34 patients with positive results on PCR(85 percent), an adverse cardiac event occurred within threemonths after the positive biopsy, and 9 of the 34 patients hadgraft loss due to coronary vasculopathy, chronic graft failure,or acute rejection. In 39 of the 115 patients with negativeresults on PCR (34 percent), an adverse cardiac event occurredwithin three months of the negative PCR finding; graft lossdid not occur in any of the patients in this group. The oddsof graft loss were 6.5 times as great among those with positiveresults on PCR (P=0.006). The detection of adenovirus was associatedwith considerably reduced graft survival (P=0.002).
Conclusions Identification of viral genome, particularly adenovirus,in the myocardium of pediatric transplant recipients is predictiveof adverse clinical events, including coronary vasculopathyand graft loss.
Source Information
From the Department of Pediatrics (Cardiology), Medical University of South Carolina, Charleston (G.S.S.); the Departments of Pediatrics (Cardiology) (J.N., N.E.B., J.A.T.), Molecular and Human Genetics (J.A.T.), and Cardiovascular Sciences (J.A.T.), Baylor College of Medicine and Texas Children's Hospital, Houston; the Departments of Ambulatory Pediatrics (R.E.C.) and Nursing (J.K.J.), Loma Linda University Children's Hospital, Loma Linda, Calif.; and the Department of Pediatrics (Cardiology), University of Washington, Seattle (G.L.R.).
Address reprint requests to Dr. Towbin at the Department of Pediatric Cardiology, Rm. 333E, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, or at jtowbin{at}bcm.tmc.edu.
Garnett, C. T., Talekar, G., Mahr, J. A., Huang, W., Zhang, Y., Ornelles, D. A., Gooding, L. R.
(2009). Latent Species C Adenoviruses in Human Tonsil Tissues. J. Virol.
83: 2417-2428
[Abstract][Full Text]
Comar, M, D'Agaro, P, Campello, C, Poli, A, Breinholt, J P III, Towbin, J A, Vatta, M
(2009). Human herpes virus 6 in archival cardiac tissues from children with idiopathic dilated cardiomyopathy or congenital heart disease. J. Clin. Pathol.
62: 80-83
[Abstract][Full Text]
Nichols, W. G., Peck Campbell, A. J., Boeckh, M.
(2008). Respiratory Viruses Other than Influenza Virus: Impact and Therapeutic Advances. Clin. Microbiol. Rev.
21: 274-290
[Abstract][Full Text]
Cooper, L. T., Baughman, K. L., Feldman, A. M., Frustaci, A., Jessup, M., Kuhl, U., Levine, G. N., Narula, J., Starling, R. C., Towbin, J., Virmani, R.
(2007). The role of endomyocardial biopsy in the management of cardiovascular disease: A Scientific Statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. Eur Heart J
28: 3076-3093
[Full Text]
Cooper, L. T., Baughman, K. L., Feldman, A. M., Frustaci, A., Jessup, M., Kuhl, U., Levine, G. N., Narula, J., Starling, R. C., Towbin, J., Virmani, R.
(2007). The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease: A Scientific Statement From the American Heart Association, the American College of Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol
50: 1914-1931
[Full Text]
Cooper, L. T., Baughman, K. L., Feldman, A. M., Frustaci, A., Jessup, M., Kuhl, U., Levine, G. N., Narula, J., Starling, R. C., Towbin, J., Virmani, R., Endorsed by the Heart Failure Society of America a,
(2007). The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease: A Scientific Statement From the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation
116: 2216-2233
[Full Text]
Potena, L., Holweg, C. T. J., Vana, M. L., Bashyam, L., Rajamani, J., McCormick, A. L., Cooke, J. P., Valantine, H. A., Mocarski, E. S.
(2007). Frequent Occult Infection with Cytomegalovirus in Cardiac Transplant Recipients despite Antiviral Prophylaxis. J. Clin. Microbiol.
45: 1804-1810
[Abstract][Full Text]
Webber, S. A.
(2007). Cytomegalovirus Infection and Cardiac Allograft Vasculopathy in Children. Circulation
115: 1701-1702
[Full Text]
Mikols, C. L., Yan, L., Norris, J. Y., Russell, T. D., Khalifah, A. P., Hachem, R. R., Chakinala, M. M., Yusen, R. D., Castro, M., Kuo, E., Patterson, G. A., Mohanakumar, T., Trulock, E. P., Walter, M. J.
(2006). IL-12 p80 Is an Innate Epithelial Cell Effector That Mediates Chronic Allograft Dysfunction. Am. J. Respir. Crit. Care Med.
174: 461-470
[Abstract][Full Text]
Perreau, M., Kremer, E. J.
(2005). Frequency, Proliferation, and Activation of Human Memory T Cells Induced by a Nonhuman Adenovirus. J. Virol.
79: 14595-14605
[Abstract][Full Text]
Burch, M
(2004). Immune suppressive treatment in paediatric myocarditis: still awaiting the evidence. Heart
90: 1103-1104
[Full Text]
Donoso Mantke, O., Meyer, R., Prosch, S., Niedrig, M.
(2004). Frequent Detection of Viral Nucleic Acids in Heart Valve Tissue. J. Clin. Microbiol.
42: 2298-2300
[Abstract][Full Text]
Keller, T. T, Mairuhu, A. T.A, de Kruif, M. D, Klein, S. K, Gerdes, V. E.A, ten Cate, H., Brandjes, D. P.M, Levi, M., van Gorp, E. C.M
(2003). Infections and endothelial cells. Cardiovasc Res
60: 40-48
[Abstract][Full Text]
Frustaci, A., Chimenti, C., Calabrese, F., Pieroni, M., Thiene, G., Maseri, A.
(2003). Immunosuppressive Therapy for Active Lymphocytic Myocarditis: Virological and Immunologic Profile of Responders Versus Nonresponders. Circulation
107: 857-863
[Abstract][Full Text]
Griffin, D. W., Donaldson, K. A., Paul, J. H., Rose, J. B.
(2003). Pathogenic Human Viruses in Coastal Waters. Clin. Microbiol. Rev.
16: 129-143
[Abstract][Full Text]
Bowles, N. E., Ni, J., Marcus, F., Towbin, J. A.
(2002). The detection of cardiotropic viruses in the myocardium of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol
39: 892-895
[Abstract][Full Text]
Brewer, L. A., Lwamba, H. C. M., Murtaugh, M. P., Palmenberg, A. C., Brown, C., Njenga, M. K.
(2001). Porcine Encephalomyocarditis Virus Persists in Pig Myocardium and Infects Human Myocardial Cells. J. Virol.
75: 11621-11629
[Abstract][Full Text]
Avery, R. K.
(2001). Viral Triggers of Cardiac-Allograft Dysfunction. NEJM
344: 1545-1547
[Full Text]