Author + information
- Sophie Mavrogeni, MD⁎ (, )
- Konstantinos Spargias, MD,
- Costas Bratis, MD,
- Genovefa Kolovou, MD,
- Evangelia Papadopoulou, MD and
- Gregory Pavlides, MD
- ↵⁎50 Esperou Street, 175-61 P. Faliro, Athens, Greece
Myocarditis represents an important cause of unexpected sudden death. Approximately half of all fatal cases are due to Coxsackie B, and most of the remainder to Coxsackie A, echovirus, and poliovirus. There are few reports about fatal cases due to Epstein-Barr virus (EBV) (1).
We evaluated with cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB) 6 patients age 35 to 68 years (2 women/4 men) without history of systemic disease or immunosuppressive treatment who presented with ventricular tachycardia (VT) and negative coronary angiogram. In 4 of 6 patients, the clinical presentation was compatible with acute myocarditis. Their symptoms included lymphadenopathy; fever; chest pain; VT and ST elevation equal to 1 mm in II, III, aVF; increase in creatine kinase MB fraction and troponin I (creatine kinase-MB fraction was 77, 92, 87, and 105 ng/ml [normal values <3.6 ng/ml] and troponin I was 8.2, 12.2, 13.5, and 15.2 ng/ml [normal values <0.10 ng/ml], respectively). One of 4 experienced a sudden death episode and was successfully resuscitated. The other 2 with a past history of EBV infection 2 years ago (confirmed by positive serology for EBV IgM antibodies during the acute infection), completely asymptomatic until admission, presented with VT and sudden death, and one of them was successfully resuscitated.
CMR was performed within 2 to 5 days after the VT. T2-weighted, early gadolinium enhanced (EGE), and late gadolinium enhanced (LGE) injection images were evaluated. The patient was considered positive for myocarditis if at least 2 of 3 imaging sequences gave positive results (2). Left ventricular function was assessed by steady-state free-precession sequence. Images were evaluated by 2 independent readers, and the kappa value was 0.83.
The EMB was performed in all of the patients because of acute myocarditis with VT in 4 of 6 and the possibility of healed myocarditis (owing to past history with EBV) or any other myocardial disease presented with VT in the other 2 of 6. Eight endomyocardial specimens were obtained from the right side of the ventricular septum of each patient (4 used for histologic evaluation and 4 for deoxyribonucleic acid/ribonucleic acid extraction to detect viral genomes). The detection of >14 infiltrating leukocytes/mm2 with myocyte damage and/or fibrosis was used for the diagnosis of active myocarditis. Healing myocarditis was considered if the inflammation was less extensive (<14 leukocytes/mm2), whereas healed myocarditis was characterized by multifocal fibrosis or scarring without inflammation (0 to 3 leukocytes/mm2, which is identical to normal myocardium). Polymerase chain reaction (PCR) was performed for viral detection (coxsackieviruses, echoviruses, adenoviruses, parvovirus B19, human cytomegalovirus, EBV, and Herpes viruses 1 to 6) (3).
CMR was positive for acute myocarditis in all patients with acute symptoms. However, in the 2 patients who presented with VT and past history of EBV, only LGE lesions in the posterior wall were identified. The left ventricular ejection fraction was reduced in 2 of 4 with acute symptoms and in 1 of 2 with past history of EBV (Table 1) (4). Histology revealed the presence of active myocarditis in all 4 patients with acute myocarditis and healed myocarditis in those with a past history of EBV infection. Myocardial PCR identified EBV in all patients. A patient with positive LGE area and active myocarditis is presented in Figure 1.
In this study, we identified VT episodes in 6 patients with current or past history of EBV infection. The clinical diagnosis was verified by both CMR and EMB, and the presence of EBV was documented by myocardial PCR. T2 and EGE images were positive only in the patients with acute myocarditis, and they were compatible with the histologic findings indicative of acute myocarditis. In contrast, in the 2 patients with a past history of EBV, CMR detected only fibrotic lesions, and the histology documented healed myocarditis, emphasizing the complementary role of the 2 techniques in myocarditis assessment.
EBV infection usually presents neurologically or hematologically, with no cardiac complications. Although it can lead to myocarditis in immunodepressed patients, it has been rarely attributed to myocarditis in immunocompetent patients. Myocardial viral genome evaluation in dilated cardiomyopathy showed a high prevalence of viruses in the myocardium (Parvo-B19 51.4%; Herpes virus 6 21.6%). However, the EBV genome was found in only 2% of patients (1).
The interesting finding in our patients was that the typical signs and symptoms of EBV infection occurred simultaneously with cardiac symptoms. Fatal myocarditis has already been described as a rare complication during acute EBV infection, but not in healed myocarditis after EBV infection. According to our findings, EBV can provoke VT by both acute and chronic myocardial inflammation.
This study has some limitations because: 1) only a small number of patients were examined; 2) children and patients with immunodeficiency and/or under immunosuppressive treatment prone to EBV infection were not included; and 3) only a short-term follow-up was performed.
In conclusion, a common virus like EBV, usually known for extracardiac complications, can provoke VT both on an acute and a chronic basis. There is a complementary association between EMB and CMR in myocarditis evaluation.
- American College of Cardiology Foundation
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