Case report

We report the case of a 13-day-old female neonate presented with cardiorespiratory arrest to the local hospital. In the early morning, she had been found unresponsive by her parents. There had been no viral prodrome or respiratory symptoms reported. An ambulance arrived five minutes later and cardiopulmonary resuscitation was commenced after confirming cardiorespiratory arrest. Cardiac rhythm demonstrated ventricular fibrillation. The infant arrived at the local emergency department only five minutes after the ambulance arrived. By this time, her rhythm was pulseless electronic activity and cardiopulmonary resuscitation was resumed. The infant received one round of intraosseous and one round of intravenous adrenaline, 60 ml/kg crystalloid fluid, intravenous antibiotics, and acyclovir. Her cardiac rhythm normalised after 20 minutes of cardiopulmonary resuscitation. On examination, her pulses were weak, there was a gallop rhythm, and a 3 cm hepatomegaly. An echocardiogram performed locally demonstrated a dilated left ventricle with severely impaired left ventricular systolic function.

She was immediately transferred to the national paediatric cardiac intensive-care unit. Echocardiogram at the tertiary hospital confirmed a structurally normal heart, severe left ventricular systolic dysfunction, with a left ventricular shortening fraction <10%, and moderate mitral regurgitation. The origin and proximal course of the coronary arteries were normal on transthoracic echocardiography. The B natriuretic peptide level measured 3060 pg/ml, troponin T 3032 ng/L, AST 265 U/L, and ALT 142 U/L. Urea and creatinine levels were normal, albumin 23 g/L, and prothrombin time was 24.1 seconds. The infant was commenced on intravenous milrinone, noradrenaline, and adrenaline. Viral myocarditis was suspected, and therefore intravenous immunoglobulin was administered. The mother had a history of coryzal symptoms, sore throat, and cough starting five days before delivery. Polymerase chain reaction studies of the infant’s blood, nasopharyngeal aspirate, and stool sample were positive for enterovirus RNA. All other microbiological, metabolic, and genetic testings for cardiomyopathy were negative.

After two months, the infant remained dependent on intravenous milrinone, noradrenaline, adrenaline, and invasive ventilation. Mild-to-moderate mitral regurgitation persisted and left ventricular shortening fraction remained <10%. Further, two courses of levosimendan were administered without any beneficial effect. Earlier in her course, an electroencephalogram showed moderate-to-severe bilateral cerebral dysfunction, and an magnetic resonance imaging (MRI) scan of the brain demonstrated two small areas of haemorrhage in the posterior fossa. A repeat MRI of the brain one and a half months after the event showed no change in the lesions, and the infant was neurologically normal on examination. Liver synthetic function had normalised and transaminase levels were normal.

She was listed for orthotopic cardiac transplantation two months after the initial presentation. It was decided not to place her on a ventricular assist device due to her small size, risk of thromboembolism/stroke, limited availability, and the difficulty in transporting the patient on a ventricular assist device by fixed-wing aircraft to the cardiac transplantation centre. In addition, despite her dependence on mechanical ventilation and inotropic support, she maintained reasonable end-organ perfusion. A month later, she received an orthotopic heart transplantation after fixed-wing air transport to Great Ormond Street in the United Kingdom. She did not require bridging to transplant in Ireland with extracorporeal membranous oxygenation or a left ventricular assist device, as she remained haemodynamically stable on intravenous inotropes and invasive ventilation. The surgery was uncomplicated and the infant recovered well. She received the standard immunosuppression and antimicrobial prophylaxis regimens in addition to co-trimoxazole and intravenous ganciclovir, as the donor was positive for toxoplasmosis and cytomegalovirus. Echocardiography demonstrated normal biventricular function with a left ventricular shortening fraction of 38%. Endomyocardial biopsy three months after the transplantation demonstrated no evidence of rejection. She has been discharged home, is asymptomatic, and making normal developmental progress.

The sections from the myocardium of the explanted heart showed extensive areas of myocyte loss with replacement fibrosis. These areas had a stellate outline with an irregular distribution throughout the full thickness of the myocardium. They corresponded to yellow areas noted macroscopically and affected the ventricular myocardium, predominantly on the left side, and also affected the atrial myocardium and septum (Fig 1). The affected areas showed extensive granular calcification and a moderate-to-heavy infiltrate of inflammatory cells, particularly plasma cells. In some areas, there were multinucleated giant cells, although well-formed granulomata were not present. The vessels were normal. There were mild dysplastic changes in the atrioventricular valves, and the mitral valve showed a large blood cyst in the anterior leaflet (Fig 1). There was a scattered chronic inflammatory cell infiltrate in the endocardium and epicardium. The atrioventricular conduction axis showed necrosis and focal haemorrhage. The appearances were those of extensive myocardial necrosis with inflammatory cell infiltration and calcification, in keeping with previous myocarditis.

Figure 1

Macroscopic image of the explanted heart demonstrating dilated left ventricular cavity with extensive areas of myocyte loss with fibrosis (yellow areas), predominantly on the left side. There was a large blood cyst in the anterior leaflet of the mitral valve.