NIH-SPONSORED WORKSHOP ON DILATED CARDIOMYOPATHY CONFERENCE REPORT National Institutes of Health–Sponsored Workshop on Inflammation and Immunity in Dilated Cardiomyopathy LESLIE T. COOPER, MD; RENU VIRMANI, MD; NORA M. CHAPMAN, PHD; ANDREA FRUSTACI, MD; RICHARD J. RODEHEFFER, MD; MADELEINE W. CUNNINGHAM, PHD; AND DENNIS M. MCNAMARA, MD Nonischemic dilated cardiomyopathy (DCM) is an uncommon cause of heart failure but has widespread importance because it is the cause of 45% of heart transplantations. Multiple experimental and clinical lines of evidence have implicated altered immunity in the pathogenesis of DCM. However, advances in the understand- ing of the mechanisms of altered immunity have not affected the diagnosis or treatment of DCM . In recognition of this problem, the National Institutes of Health sponsored an expert workshop with 2 aims: to review the current understanding of inflammation and immunity as they relate to DCM and to identify the most promising areas for future clinical research efforts in the field. This report summarizes the scientific opportunities, perceived needs and barriers, and workshop recommendations on research directions in DCM. The major recommendations from the members of the workshop are organized according to the following themes: cardio- tropic viruses, innate and acquired immune responses, environ- mental factors, novel diagnostics, and novel therapeutics. Mayo Clin Proc. 2006;81(2):199-204 DCM = dilated cardiomyopathy; GPx = glutathione peroxidase; MRI = magnetic resonance imaging; NIH = National Institutes of Health; qPCR = quantitative polymerase chain reaction; qRT-PCR = quantita- tive reverse transcriptase–PCR; TE = trace element D ilated cardiomyopathy (DCM) is an uncommon cause of heart failure but has widespread importance be- cause it is the cause of 45% of heart transplantations. 1 The last National Institutes of Health (NIH)–sponsored expert workshop on this subject was held in 1989 and identified the need for investigation into the immunologic basis of the disease. 2 Since then, exceptional strides have been made in our understanding of the immunology and pathophysiology of viral and autoimmune myocarditis. 3 Most of these ad- From the Division of Cardiovascular Diseases, Mayo Clinic College of Medi- cine, Rochester, Minn (L.T.C., R.J.R.); International Registry of Pathology, Gaithersburg, Md (R.V.); Department of Pathology and Laboratory Medi- cine, University of Nebraska Medical Center, Omaha (N.M.C.); Department of Heart and Great Vessels “Attilio Reale” La Sapienza University and National Institute for Infectious Diseases “Lazzaro Spallanzani,” Rome, Italy (A.F.); University of Oklahoma Health Sciences Center, Oklahoma City (M.W.C.); and Cardiovascular Division, University of Pittsburgh Medical Center, Pittsburgh, Pa (D.M.M.). The participating investigators are listed at the end of this artic le . This article was funded by the National Heart, Lung, and Blood Institute and National Institutes of Health Office of Rare Diseases grant R13 HL074877- 01, the American Heart Association Clinical Cardiology Council, and the American Registry of Pathology. Address reprint requests and correspondence to Leslie T. Cooper, MD, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905 (e-mail: cooper.leslie@mayo.edu). © 2006 Mayo Foundation for Medical Education and Research vances have been made through the use of inbred and transgenic rodent models. Advances in clinical treatment and diagnosis of myocarditis and DCM have lagged behind the advances in our understanding of disease mechanisms. The workshop was organized to address the need to translate advances at the bench into bedside medicine. Experts from a range of relevant specialties, including virology, biochemistry, immunology, pathology, and clini- cal cardiology, met with representatives of the NIH on May 21 and 22, 2004. The conference was organized into themes consisting of cardiotropic viruses, innate and ac- quired immunity, environmental factors, novel diagnostics, and novel therapeutics. Within each theme, the participants identified perceived challenges and opportunities and made recommendations for support of future research. This re- port summarizes the discussions and recommendations from that conference. CARDIOTROPIC VIRUSES Viral myocarditis is pathogenically determined by at least 3 factors: (1) the virus and its receptor, (2) the host immune system, and (3) cardiac remodeling. 4 In the past 18 years, we have seen important advances in our ability to detect cardiotropic viruses from fresh and frozen heart tissue us- ing in situ hybridization, quantitative polymerase chain reaction (qPCR), nested qPCR, and most recently quantita- tive reverse transcriptase–PCR (qRT-PCR). The latest tech- nologies can detect 1 to 10 gene copies present in myocar- dium. These rapid advances in technology have changed the sensitivity of molecular techniques for viral pathogens and have provided both challenges and opportunities. New viral pathogens have emerged in the past decade, including adenovirus, Epstein-Barr virus, cytomegalovirus, hepatitis C, and most recently parvovirus B19. 5 Enterovirus serotypes have been identified as different from the 64 serotypes recognized previously. 6-8 Given the high rate of enterovirus recombination, the current diagnostic method of qRT-PCR of conserved regions of the 5′ nontranslated region cannot discriminate among the currently recognized enterovirus serotypes. 6 Portions of the enterovirus genome other than the 5′ nontranslated region could be explored for unique and conserved sequences. Such studies may allow for a molecular identification of the known serotypes or Mayo Clin Proc. • February 2006;81(2):199-204 • www.mayoclinicproceedings.com 199 For personal use. Mass r For personal use. Mass r epr epr oduce only with per oduce only with permission fr mission fr om om Mayo Clinic Pr Mayo Clinic Pr o c e e din o c e e dings. s.