928
Correspondence
JACC Vol. 55, No. 9, 2010
March 2, 2010:926–33
CORRESPONDENCE
Research Correspondence
Fulminant Myocarditis Associated With
Pandemic H1N1 Influenza A Virus in Children
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
a 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).
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.
*András Bratincsák, MD, PhD
*Rady Children’s Hospital–San Diego
University of California San Diego, School of Medicine
3020 Children’s Way
MC5004
San Diego, California 92123
E-mail: [email protected]
Howaida G. El-Said, MD, PhD
John S. Bradley, MD
Katayoon Shayan, MD
Paul D. Grossfeld, MD
Christopher R. Cannavino, MD
doi:10.1016/j.jacc.2010.01.004
JACC Vol. 55, No. 9, 2010
March 2, 2010:926–33
Figure 1
Correspondence
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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.
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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