CORRESPONDENCE: RESEARCH CORRESPONDENCE
Fulminant Myocarditis Associated With Pandemic H1N1 Influenza A Virus in Children
András Bratincsák, MD, PhD*,
Howaida G. El-Said, MD, PhD,
John S. Bradley, MD,
Katayoon Shayan, MD,
Paul D. Grossfeld, MD and
Christopher R. Cannavino, MD
* Rady Children's Hospital–San Diego, University of California San Diego, School of Medicine, 3020 Children's Way, MC5004, San Diego, California 92123 (Email: bratiandris{at}yahoo.com).
To the Editor: Acute myocarditis is a well-recognized, albeit rare, manifestation of numerous viral infections (1) with a broad spectrum of symptoms and clinical features (2). Fulminant myocarditis may present with fatal arrhythmias, atrioventricular block, and/or varying degrees of cardiogenic shock (3). The prevalence of myocardial involvement in influenza infection ranges from 0 to 11% depending on the diagnostic criteria used to define myocarditis (4). Fulminant myocarditis is an uncommon complication, typically diagnosed in association with circulatory collapse or at autopsy in patients with influenza-associated fatal outcomes (5). A few case reports and series (6–8) represent the incidental diagnoses of influenza-associated acute fulminant myocarditis, but the true prevalence remains unknown.
Here we present the first known report of acute myocarditis in pediatric population associated with the present pandemic H1N1 influenza A virus infection. Four cases occurred within a 30-day period, and 3 of them were diagnosed as fulminant myocarditis with fatal or near-fatal outcomes.
A retrospective chart review was conducted on all patients admitted to Rady Children's Hospital–San Diego with the diagnosis of H1N1 influenza A infection during October 2009. Criteria for fulminant myocarditis included echocardiographic and clinical evidence of severely decreased left ventricular systolic function and/or lymphocytic infiltration of the myocardium documented at autopsy.
Within a 30-day period, 80 children were admitted with H1N1 influenza A infection to Rady Children's Hospital–San Diego. Serum troponin I and creatine phosphokinase myocardial band levels were obtained in 11 children, and echocardiography was performed in 8 children. We included 4 H1N1 influenza–associated myocarditis cases based on elevated cardiac enzymes (n = 2), significant acute decrease in left ventricular systolic function demonstrated by the echocardiogram (n = 3), or histologic evidence of severe myocarditis (n = 1) (Fig. 1A). Three children presented with fulminant myocarditis, 1 with a fatal outcome and 2 requiring extracorporeal membrane oxygenation support. None of the children with fulminant myocarditis had evidence of sepsis or bacterial infection (negative blood, urine, and tracheal aspirate cultures). Two of the 3 children with decreased systolic function experienced recovery in 5 to 7 days (Figs. 1E and 1F). All 4 children had a positive rapid influenza enzyme immunoassay test result from a nasopharyngeal swab sample that was subsequently confirmed as H1N1 by reverse-transcriptase polymerase chain reaction performed at the San Diego County Department of Health (Fig. 1A).
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Figure 1 Acute Myocarditis Associated With H1N1 Influenza A Infection
(A) Demographics, symptoms, tests, and complications of 4 children with influenza-associated acute myocarditis. (B) Severe myocardial damage demonstrated in the interventricular septum with mononuclear cellular infiltration. (C) Enlarged area from B shows a large number of lymphocytes and macrophages infiltrating the myocardium (arrow) with surrounding cardiomyocyte necrosis. (D) Lymphocytic infiltration in the area of the atrioventricular (AV) node (*). (E) Severe dilation and poor systolic function of the left ventricle (LV) on a 2-dimensional and M-mode echocardiogram with an ejection fraction (EF) of 12%. (F) Resolution of left ventricular (LV) systolic function after 5 days of extracorporeal membrane oxygenation (ECMO) support demonstrated on 2-dimensional and M-mode echocardiogram with an improved EF of 68%. BP = blood pressure; bpm = beats/min; EIA = enzyme immunoassay; HR = heart rate; IVS = interventricular septum; LA = left atrium; RA = right atrium; rtPCR = reverse-transcriptase polymerase chain reaction; RV = right ventricle.
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Fulminant myocarditis due to viral infection is an uncommon form of acute myocarditis (2,3). Influenza A virus–associated fulminant myocarditis is exceedingly rare, with only a few cases reported in the literature (4,5). We report the first 4 cases of acute myocarditis in children associated with the pandemic H1N1 influenza A virus, all occurring within a 30-day period.
Our tertiary care hospital serves a geographic region that includes approximately 800,000 children. During the past 3 years, there was an annual average of 2 cases of acute myocarditis due to suspected viral etiology, none of which had evidence of influenza infection. Within a 30-day period in October 2009, there were 3 cases of acute fulminant myocarditis and 1 case of acute perimyocarditis at Rady Children's Hospital–San Diego, all associated with confirmed H1N1 influenza A infection. There was serologic, echocardiographic, and/or histologic evidence of myocardial involvement in all cases (Fig. 1A). Three children had echocardiographic evidence of an acutely decreased myocardial function. One child died likely due to acute atrioventricular block, as suggested by severe lymphocytic infiltration of the conduction system (Figs. 1B to 1D). Two children required extracorporeal membrane oxygenation support with gradual improvement of the ventricular systolic function over a 1-week period (Figs. 1E and 1F), which is typically observed in patients with fulminant myocarditis (2).
The prevalence of influenza-associated fulminant myocarditis is not known because of the lack of comprehensive screening, with only a handful of clinical cases and autopsy findings reported in the literature (5–8). Our documented 4 cases within a 30-day period, compared with our previous experience, raise the possibility that the novel H1N1 influenza A virus is more commonly associated with a severe form of myocarditis than previously encountered influenza strains.
Our observations warrant a high index of suspicion for myocarditis in children with H1N1 influenza A infection. Early detection and aggressive management are paramount. Timely intervention with circulatory support may decrease morbidity and mortality, with the potential for a favorable cardiac prognosis.
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Footnotes
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Please note: Leslie Cooper, MD, served as Guest Editor for this paper. Drs. Bratincsák, El-Said, Grossfeld, and Cannavino contributed equally to this report.
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References
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1 Bowles NE, Ni J, Kearney DL, et al. Detection of viruses in myocardial tissues by polymerase chain reaction. Evidence of adenovirus as a common cause of myocarditis in children and adults. J Am Coll Cardiol 2003;42:466-472.[Abstract/Free Full Text]2 Lieberman EB, Hutchins GM, Herskowitz A, Rose NR, Baughman KL. Clinicopathologic description of myocarditis J Am Coll Cardiol 1991;18:1617-1626.[Abstract] 3 Cooper Jr LT. Myocarditis N Engl J Med 2009;360:1526-1538.[CrossRef][Web of Science][Medline] 4 Mamas MA, Fraser D, Neyses L. Cardiovascular manifestations associated with influenza virus infection Int J Cardiol 2008;130:304-309.[CrossRef][Web of Science][Medline] 5 Guarner J, Paddock CD, Shieh WJ, et al. Histopathologic and immunohistochemical features of fatal influenza virus infection in children during the 2003–2004 season Clin Infect Dis 2006;43:132-140.[Abstract/Free Full Text] 6 Walker OJ. Pathology of influenza-pneumonia J Lab Clin Med 1919;5:22. 7 Adams CW. Postviral myopericarditis associated with the influenza virus: report of eight cases Am J Cardiol 1959;4:56-67.[CrossRef][Web of Science][Medline] 8 Onitsuka H, Imamura T, Miyamoto N, et al. Clinical manifestations of influenza a myocarditis during the influenza epidemic of winter 1998–1999 J Cardiol 2001;37:315-323.[Medline]
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