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(Circulation. 2004;110:3534-3539.)
© 2004 American Heart Association, Inc.

Heart Failure

Intramyocyte Detection of Epstein-Barr Virus Genome by Laser Capture Microdissection in Patients With Inflammatory Cardiomyopathy

Cristina Chimenti, MD, PhD; Andrea Russo, MD, PhD; Maurizio Pieroni, MD; Fiorella Calabrese, MD; Romina Verardo, BSc; Gaetano Thiene, MD; Matteo A. Russo, MD; Attilio Maseri, MD; Andrea Frustaci, MD

From the Cardiothoracic and Vascular Department, Vita e Salute University (C.C., M.P., A.M.) Milan, Italy; the Biopathology and Diagnostic Imaging Department, Torvegata University and IRCC Regina Elena Institute (A.R.), Rome, Italy; the Department of Pathology, University of Padua (F.C., G.T.) Padua, Italy; the Department of Cardiology, Catholic University (R.V., A.F.) Rome, Italy; and the Pathology and Experimental Medicine Department, La Sapienza University and San Raffaele Pisana Institute (M.A.R.) Rome, Italy.

Reprint requests to Andrea Frustaci, MD, Cardiology Department, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy. E-mail biocard{at}rm.unicatt.it

Received June 6, 2004; revision received September 18, 2004; accepted September 30, 2004.

Background— The causal role of Epstein-Barr virus (EBV) in inflammatory cardiomyopathy (IC) is still unclear, because this virus is present in latently infected circulating B lymphocytes in 90% of adults. Laser capture microdissection (LCM) has been applied on endomyocardial biopsy samples from patients with IC to assess the presence of EBV genome in separately dissected lymphocytes and myocytes.

Methods and Results— Among 142 patients with cardiac dilation and dysfunction and a histological and immunohistochemical diagnosis of myocarditis, 44 had a myocardial viral infection detected by polymerase chain reaction on frozen endomyocardial biopsy samples. In 9 of them, the virus detected was EBV. LCM was performed on 5-µm-thick paraffin sections of EBV-infected hearts. Lymphocytes and myocytes were microdissected and analyzed separately by polymerase chain reaction analysis on DNA extracted from the collected cells. Blood and myocardial samples from patients with positive and negative serology for EBV were used as controls. EBV genome was detected in myocytes but not in infiltrating lymphocytes of patients, nor in myocardial samples from controls. Despite full conventional antifailure therapy, a progressive cardiac dilation and dysfunction was documented in patients with EBV-related IC at a mean of 31±14 months of follow-up.

Conclusions— Intramyocyte detection of EBV can be obtained by LCM in up to 6.3% of patients with IC. This supports a cytopathic EBV role and suggests the opportunity for an antiviral/immunomodulatory therapy.

Key Words: cardiomyopathy • myocarditis • viruses • heart failure • microdissection

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