doi:10.1016/j.jacc.2010.01.004 published online Feb 10, 2010; J. Am. Coll. Cardiol.

Grossfeld, and Christopher R. Cannavino András Bratincsák, Howaida G. El-Said, John S. Bradley, Katayoon Shayan, Paul D.

ChildrenFulminant Myocarditis Associated With Pandemic H1N1 Influenza A Virus in

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ARTICLE IN PRESS

CORRESPONDENCE

ResearchCorrespondence Fulminant Myocarditis Associated With

Pandemic H1N1 Influenza A Virus in Children

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o the Editor: Acute myocarditis is a well-recognized, albeit rare,anifestation of numerous viral infections (1) with a broad

pectrum of symptoms and clinical features (2). Fulminant myo-arditis may present with fatal arrhythmias, atrioventricular block,nd/or varying degrees of cardiogenic shock (3). The prevalence ofyocardial involvement in influenza infection ranges from 0 to

1% depending on the diagnostic criteria used to define myocar-itis (4). Fulminant myocarditis is an uncommon complication,ypically diagnosed in association with circulatory collapse or atutopsy in patients with influenza-associated fatal outcomes (5). Aew case reports and series (6–8) represent the incidental diagnosesf influenza-associated acute fulminant myocarditis, but the truerevalence remains unknown.

Here we present the first known report of acute myocarditis inediatric population associated with the present pandemic H1N1nfluenza A virus infection. Four cases occurred within a 30-dayeriod, and 3 of them were diagnosed as fulminant myocarditisith fatal or near-fatal outcomes.A retrospective chart review was conducted on all patients

dmitted to Rady Children’s Hospital–San Diego with the diag-osis of H1N1 influenza A infection during October 2009.riteria for fulminant myocarditis included echocardiographic and

linical evidence of severely decreased left ventricular systolicunction and/or lymphocytic infiltration of the myocardium doc-mented at autopsy.

Within a 30-day period, 80 children were admitted with H1N1nfluenza A infection to Rady Children’s Hospital–San Diego.erum troponin I and creatine phosphokinase myocardial band

evels were obtained in 11 children, and echocardiography waserformed in 8 children. We included 4 H1N1 influenza–ssociated myocarditis cases based on elevated cardiac enzymesn � 2), significant acute decrease in left ventricular systolicunction demonstrated by the echocardiogram (n � 3), or histo-ogic evidence of severe myocarditis (n � 1) (Fig. 1A). Threehildren presented with fulminant myocarditis, 1 with a fatalutcome and 2 requiring extracorporeal membrane oxygenationupport. None of the children with fulminant myocarditis hadvidence of sepsis or bacterial infection (negative blood, urine, andracheal aspirate cultures). Two of the 3 children with decreasedystolic function experienced recovery in 5 to 7 days (Figs. 1E and 1F).ll 4 children had a positive rapid influenza enzyme immunoassay test

esult from a nasopharyngeal swab sample that was subsequentlyonfirmed as H1N1 by reverse-transcriptase polymerase chain reac-ion performed at the San Diego County Department of HealthFig. 1A).

Fulminant myocarditis due to viral infection is an uncommonorm of acute myocarditis (2,3). Influenza A virus–associatedulminant myocarditis is exceedingly rare, with only a few cases

eported in the literature (4,5). We report the first 4 cases of acute

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yocarditis in children associated with the pandemic H1N1nfluenza A virus, all occurring within a 30-day period.

Our tertiary care hospital serves a geographic region thatncludes approximately 800,000 children. During the past 3ears, there was an annual average of 2 cases of acute myocar-itis due to suspected viral etiology, none of which had evidencef influenza infection. Within a 30-day period in October 2009,here were 3 cases of acute fulminant myocarditis and 1 case ofcute perimyocarditis at Rady Children’s Hospital–San Diego,ll associated with confirmed H1N1 influenza A infection.here was serologic, echocardiographic, and/or histologic evi-ence of myocardial involvement in all cases (Fig. 1A). Threehildren had echocardiographic evidence of an acutely decreasedyocardial function. One child died likely due to acute atrio-

entricular block, as suggested by severe lymphocytic infiltrationf the conduction system (Figs. 1B to 1D). Two childrenequired extracorporeal membrane oxygenation support withradual improvement of the ventricular systolic function over a-week period (Figs. 1E and 1F), which is typically observed inatients with fulminant myocarditis (2).

The prevalence of influenza-associated fulminant myocarditis isot known because of the lack of comprehensive screening, withnly a handful of clinical cases and autopsy findings reported in theiterature (5–8). Our documented 4 cases within a 30-day period,ompared with our previous experience, raise the possibility thathe novel H1N1 influenza A virus is more commonly associatedith a severe form of myocarditis than previously encountered

nfluenza strains.Our observations warrant a high index of suspicion for myocar-

itis in children with H1N1 influenza A infection. Early detectionnd aggressive management are paramount. Timely interventionith circulatory support may decrease morbidity and mortality,ith the potential for a favorable cardiac prognosis.

Andras Bratincsak, MD, PhD

Rady Children’s Hospital–San Diegoniversity of California San Diego, School of Medicine020 Children’s WayC5004

an Diego, California 92123-mail: bratiandris@yahoo.com

owaida G. El-Said, MD, PhDohn S. Bradley, MDatayoon Shayan, MDaul D. Grossfeld, MDhristopher R. Cannavino, MD

doi:10.1016/j.jacc.2010.01.004

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2 Correspondence JACC Vol. 55, No. 9, 2010March 2, 2010:000–000

ARTICLE IN PRESS

lease note: Leslie Cooper, MD, served as Guest Editor for this paper. Drs.ratincsak, El-Said, Grossfeld, and Cannavino contributed equally to this report.

EFERENCES

. Bowles NE, Ni J, Kearney DL, et al. Detection of viruses in myocardialtissues by polymerase chain reaction. Evidence of adenovirus as acommon cause of myocarditis in children and adults. J Am Coll Cardiol2003;42:466–72.

. Lieberman EB, Hutchins GM, Herskowitz A, Rose NR, BaughmanKL. Clinicopathologic description of myocarditis. J Am Coll Cardiol1991;18:1617–26.

Figure 1 Acute Myocarditis Associated With H1N1 Influenza A Infection

(A) Demographics, symptoms, tests, and complications of 4 children with influenzinterventricular septum with mononuclear cellular infiltration. (C) Enlarged area frodium (arrow) with surrounding cardiomyocyte necrosis. (D) Lymphocytic infiltrationfunction of the left ventricle (LV) on a 2-dimensional and M-mode echocardiogramfunction after 5 days of extracorporeal membrane oxygenation (ECMO) support dem68%. BP � blood pressure; bpm � beats/min; EIA � enzyme immunoassay; HR �

� reverse-transcriptase polymerase chain reaction; RV � right ventricle.

. Cooper LT Jr. Myocarditis. N Engl J Med 2009;360:1526–38.

content.onlinejacDownloaded from

. Mamas MA, Fraser D, Neyses L. Cardiovascular manifestations asso-ciated with influenza virus infection. Int J Cardiol 2008;130:304–9.

. Guarner J, Paddock CD, Shieh WJ, et al. Histopathologic andimmunohistochemical features of fatal influenza virus infection inchildren during the 2003–2004 season. Clin Infect Dis 2006;43:132– 40.

. Walker OJ. Pathology of influenza-pneumonia. J Lab Clin Med1919;5:22.

. Adams CW. Postviral myopericarditis associated with the influenzavirus: report of eight cases. Am J Cardiol 1959;4:56–67.

. Onitsuka H, Imamura T, Miyamoto N, et al. Clinical manifestations ofinfluenza a myocarditis during the influenza epidemic of winter 1998–

ciated acute myocarditis. (B) Severe myocardial damage demonstrated in thehows a large number of lymphocytes and macrophages infiltrating the myocar-area of the atrioventricular (AV) node (*). (E) Severe dilation and poor systolic

n ejection fraction (EF) of 12%. (F) Resolution of left ventricular (LV) systolicated on 2-dimensional and M-mode echocardiogram with an improved EF oft rate; IVS � interventricular septum; LA � left atrium; RA � right atrium; rtPCR

a-assom B sin the

with aonstrhear

1999. J Cardiol 2001;37:315–23.

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doi:10.1016/j.jacc.2010.01.004 published online Feb 10, 2010; J. Am. Coll. Cardiol.

Grossfeld, and Christopher R. Cannavino András Bratincsák, Howaida G. El-Said, John S. Bradley, Katayoon Shayan, Paul D.

ChildrenFulminant Myocarditis Associated With Pandemic H1N1 Influenza A Virus in

This information is current as of February 11, 2010

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