Nathan, Meena*; Walsh, Rowan†; Hardin, Joel T.†; Einzig, Stanley†; Connor, Brian O.†; Balaguru, Duraisamy†; Verma, Rajiv†; Starr, Joanne P.*
From the Divisions of *Pediatric Cardiac Surgery; and †Pediatric Cardiology, Children’s Hospital of New Jersey at Newark Beth Israel Medical Center, Newark, New Jersey.
Submitted for consideration May 2008; accepted for publication in revised form July 2008.
Presented in part at the Fourth International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion, May 22–24, 2008, Portland, Oregon.
Reprint Requests: Meena Nathan, MD, Children’s Hospital of New Jersey, 201, Lyons Avenue, Newark NJ 07112. Email: firstname.lastname@example.org.
Neonatal entero-viral sepsis is a rare but fulminant infection with multisystem involvement, often presenting with hepatitis, meningo-encephalitis, disseminated intravascular coagulation (DIC), and myocarditis. Neonatal myocarditis often proves fatal. We report here a case of neonatal enteroviral myocarditis with multisystem organ failure and ischemic cardiomyopathy that was managed medically.
An 8-day-old, 2.64 kg male infant was transferred to our center for further management of resistant narrow complex tachycardia and cardiogenic shock. Rectal and nasal cultures were positive for enterovirus. Upon admission to our institution sustained tachycardia with nonspecific strain pattern at a rate of 200/min was noted.
Echocardiogram (Figure 1) revealed biventricular dysfunction [left ventricular fractional shortening (LVFS) 16%]; normal LV dimensions (17 mm, Z score of +0.7), segmental wall motion abnormality, and diffuse coronary ectasia. Cardiac catheterization revealed normal origin and course of coronary arteries. There was no angiographic demonstration of a coronary fistula. The distribution and caliber of the left anterior descending (LAD) artery appeared small and inadequate for age. Laboratory data were consistent with ongoing hepatic dysfunction, disseminated intravascular coagulation, worsening renal function, and evidence of myocardial damage with a troponin level of 65.6 ng/ml (Figure 2). He was managed with multiple inotropes, aggressive diuretic therapy and mechanical ventilation. He could not enter the Pleconaril trial as it would have entailed transfer to another facility lacking Extracorporeal Membrane Oxygenation (ECMO) support. ECMO as a bridge to either recovery or transplantation was deferred as active viral infection made him ineligible for listing for transplantation. With continued conventional management he was weaned off inotropes and mechanical ventilation over a period of 10 weeks. There was echocardiographic evidence of progressive cardiomegaly, left ventricular free wall and basal septum akinesis with evidence of endocardial fibroelastosis. (Echo bright areas in septum and LV free wall). An interim computerized tomography of the chest (Figure 3) revealed calcification of the left anterior descending artery and endocardial, myocardial and pericardial calcification. He was discharged home after a 13 week hospitalization. His most recent echocardiogram revealed LV diastolic diameter of 2.7 cm (Z score of +3), left venricular fractional shortening of 23%, moderate mitral regurgitation, and akinesis of LV posterior wall and basal septum. He is receiving furosemide, enalapril and digoxin. He is being evaluated for cardiac transplantation.
Neonatal enteroviral infection is often fulminant and fatal if associated with multisystem organ failure. Mortality rates with myocarditis have been reported at 50%–75%, despite antiviral (Pleconaril) therapy.1,2 The association of myocarditis and hepatitis carries the highest risk of fatality.2–4 There have been a few case reports of neonatal enteroviral myocarditis presenting with myocardial infarction,5–7 including a rare report in an adult.8 The fulminant form of neonatal enteroviral infection typically presents with a combination of sepsis, meningoencephalitis, myocarditis, pneumonia, hepatitis, and coagulopathy.2
Presentation is usually in the first 2 weeks of life and risk factors include antepartum or peripartum maternal illness. Prematurity is another important risk factor.2 Most neonates have a positive serum viral culture. Enteroviral myocarditis can present as congestive heart failure, arrhythmias or myocardial infarction. Mortality rates in neonatal enteroviral infections have variably been reported as low as 0% and as high as 83%. The highest mortality occurs with myocarditis and hepatitis.2 Long-term outcome from enteroviral myocarditis varies between complete recovery to progressive cardiomyopathy, chronic calcific myocarditis, chronic heart failure, and persistent arrhythmias. Therapy consists of supportive care in conjunction with immunoglobulin infusions in the acute phase. There have been anecdotal reports of improved outcomes with pleconaril therapy.
Currently there is an ongoing trial on the utility of pleconaril in infants and neonates2 with severe enteroviral infection. Bryant et al.1 reported a series of 10 neonatal coxsackie B infections over a 3 month period in a regional center in Australia. Eight infants had multi-system organ disease and two of the four who presented with myocarditis died. All infants with severe infection presented in the first week of life and history revealed symptoms of maternal infection before delivery in this group of neonates. Three of the four who presented with myocarditis had rhythm disturbances. Two died despite pleconaril therapy. Mechanical support in the form of ECMO was not used in this series.
Inwald et al. reported on a series of seven neonates with enteroviral myocarditis, admitted to their intensive care unit over a 2 year period.3 All patients had ischemia on electrocardiogram and echocardiogram revealed structurally normal hearts with dilated left ventricles with poor contractility with a mean fractional shortening of about 10%. Four of these seven infants required ECMO (used as a bridge to recovery) and three of them succumbed (two immediate and one late death). The sole survivor in this group recovered normal function. The three children who were managed without mechanical cardiac support survived. One recovered normal function, two are on anti failure therapy. Of note, this group also showed echo bright areas in the septum consistent with scarring similar to our patient. Lin et al.4 reported on a series of all neonatal enteroviral infections in their hospital over a 10 year period. In their series, they had seven cases of myocarditis, all associated with severe hepatitis and coagulopathy and three with additional evidence of meningitis. Five of these seven succumbed.
Enteroviral myocarditis especially when associated with multi-organ involvement is often fatal. Our patient highlights the fact that medical management of a newborn with fulminant enteroviral myocarditis is possible. Short term mechanical support in the form of ECMO remains an excellent option as a bridge to recovery or transplantation in severe cardiogenic shock. However, because of its inherent risk of bleeding and thrombotic complications with time, it may not be applicable in patients who will require prolonged support. Medical management may not mitigate long term disability from prolonged low cardiac output state. Therefore, better means of long term mechanical support in the neonatal period would be useful for these rare diagnoses.
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