Author + information
- Published online June 5, 2017.
- Daniel S. Chertow, MD, MPH∗ (, )
- Richard W. Childs, MD,
- Andrew E. Arai, MD and
- Richard T. Davey Jr., MD
- ↵∗Critical Care Medicine Department, Clinical Center, National Institutes of Health, Department of Health and Human Services, 10 Center Drive, Room 2C-145, Bethesda, Maryland 20892-1662
In March 2015, a 34-year-old, previously healthy male health care worker was evacuated from Sierra Leone to the National Institutes of Health Clinical Research Center for the management of severe Ebola virus disease (EVD) (1). The patient arrived 7 days after initial symptom onset with high fever and asthenia. His clinical course was complicated by severe meningoencephalitis and sequential organ failure despite meticulous attention to fluid and electrolyte status and absence of hypotension. Daily bedside echocardiograms during peak illness did not reveal gross myocardial dysfunction, although cardiac ejection fractions were not specifically assessed. On days 17 through 18 of clinical illness, the patient developed QTc prolongation of up to 600 ms that resolved with discontinuation of Propofol administration.
Cardiac magnetic resonance (CMR) on clinical illness day 32, performed in the setting of improved clinical status and following resolution of viremia, showed mild diffuse left ventricular hypokinesis, an ejection fraction of 52% (normal 55% to 75%), and abnormalities in T1 and extracellular volume fraction (ECV) localized in the basal lateral wall. These findings were consistent with myocardial inflammation or edema (Figure 1). Repeat CMR 11 weeks later showed persistent mild diffuse hypokinesis with an ejection fraction of 51%. Gadolinium-enhanced imaging revealed a new small focus of atypical enhancement in the basal wall consistent with fibrosis and resolution of abnormalities previously seen in the surrounding myocardium. This is the first reported CMR in EVD. Mild myocardial dysfunction and subtle findings of edema or inflammation with evidence of progression to fibrosis suggest the presence of myocarditis.
Gold standard diagnostic criteria for viral myocarditis require endomyocardial biopsy using standardized histopathological (Dallas criteria) and immunohistochemical diagnostic criteria (2). CMR, however, is a valuable noninvasive modality for detection of myocarditis with high specificity (91%) and positive predictive value (91%) when 2 of 3 CMR characteristics listed in the Lake Louise criteria are present (2). Lake Louise criteria include detection of early capillary leakage on the basis of T1-weighted early gadolinium enhancement, detection of necrosis and fibrosis on the basis of late gadolinium enhancement (LGE), and detection of edema or hyperemia by T2-weighted imaging (2). In our patient, mild myocardial dysfunction with evidence of myocardial edema or inflammation (T1 and ECV abnormalities) in the basal lateral wall of the left ventricle during initial CMR, and evidence of evolution to fibrosis (LGE) in the basal wall on follow-up CMR (Figure 1) are highly specific for myocarditis.
Although endomyocardial biopsy has not been reported in EVD, post-mortem immunohistochemistry examination in fatal cases shows abundant viral antigen in the endocardium, endothelium, and extracellular in the sub-endocardium (3). Myocarditis due to viruses other than Ebola, prominently enteroviruses, ranges in clinical severity from mild infection to progressive dilated cardiomyopathy, cardiogenic shock, and fatal arrhythmias. Whether QT prolongation in our patient was related to myocarditis is not possible to discern. However, QT prolongation is frequently observed in infectious and noninfectious inflammatory conditions, was the most common electrocardiogram finding among 186 patients with myocarditis (∼25% of cases), and predicted a poor clinical outcome, including cardiac death, and may be attributable to inflammatory cytokines (4). The contribution of viral myocarditis to myocardial dysfunction and predisposition to fatal arrhythmias in the acute setting of EVD or myocardial dysfunction in long-term survivors requires further evaluation.
Please note: The Intramural Research Programs of National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute, National Institutes of Health, supported this work. The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. Dr. Arai has research agreements with Siemens and Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation