Discussion

Fulminant myocarditis is a rare, rapidly progressive, and potentially fatal condition, with viral infections constituting one of its most common causes. While parvovirus B19, coxsackievirus, adenovirus, and enterovirus are frequently identified viral agents, rare pathogens such as human metapneumovirus, as detected in our patient, may also be responsible. ^{Reference Maisch, Ruppert and Pankuweit2,Reference Schultz, Hilliard, Cooper and Rihal8}

Human metapneumovirus, first identified in 2001, belongs to the Paramyxoviridae family and is primarily associated with lower respiratory tract infections such as bronchiolitis and pneumonia. It is predominantly seen in the paediatric population and tends to peak at the end of winter and beginning of spring. Although infrequent, it has been implicated in severe extra-pulmonary manifestations such as myocarditis, which can follow a fulminant course. ^{Reference van den Hoogen, de Jong and Groen9,Reference Panda, Mohakud, Pena and Kumar10} The first report of human metapneumovirus-induced myocarditis appeared in 2015. ^{Reference Weinreich, Jabbar, Malguria and Haley5} To date, only two paediatric cases presenting with fulminant myocarditis associated with human metapneumovirus and managed with extracorporeal membrane oxygenation support have been documented in the literature—one involving an immunocompetent 11-year-old and the other a 14-year-old immunocompromised patient. ^{Reference Makhlouf, Peipoch and Duport3,Reference Owensby, Tracy and C.C.R.N.11} In our case, human metapneumovirus was the only pathogen detected and, to our knowledge, this was the second reported case of fulminant myocarditis requiring extracorporeal membrane oxygenation support in an immunocompetent paediatric patient.

The diagnosis of myocarditis is established through clinical presentation, laboratory findings, echocardiography, and cardiac MRI. The gold standard remains endomyocardial biopsy, although its diagnostic utility and necessity remain subjects of debate. Currently, a clinical diagnosis based on symptomatology is more frequently utilised in practice. ^{Reference Hang, Chen, Seubert and Wang1,Reference Maisch, Ruppert and Pankuweit2} In our patient, due to the presence of cardiogenic shock at presentation and persistent haemodynamic instability necessitating extracorporeal membrane oxygenation support within the first 12 hours of admission, neither cardiac MRI nor endomyocardial biopsy could be performed. In such critically ill patients, fulminant myocarditis can be diagnosed based on clinical, laboratory, and echocardiographic findings alone.

The pathophysiology is not fully elucidated, which limits the evidence base for its treatment. A dysregulated immune response and cytokine storm are believed to play a central role. Myocardial contractility is also dependent on mitochondrial function. The cytokine storm may impair myocardial contractility directly by causing necrosis and indirectly by disrupting mitochondrial energy production. ^{Reference Kazanski, Makarenko, Mladenov and Kamkin12} As a result, immunomodulatory agents are used despite the lack of definitive evidence. ^{Reference Mason, OConnell and Herskowitz13}

Emapalumab is a monoclonal antibody targeting interferon-gamma, approved by the FDA for the treatment of primary hemophagocytic lymphohistiocytosis. Previous literature has also highlighted the role of interferon-gamma blockage with emapalumab in the management of macrophage activation syndrome and secondary hemophagocytic lymphohistiocytosis, supporting its use in life-threatening, refractory cases. ^{Reference Henderson and Cron14} In our patient, immunoregulation was attempted firstly with a combination of intravenous immunoglobulin, methylprednisolone and anakinra. Despite this treatment, his clinical condition worsened. According to the 2016 EULAR/ACR/PRINTO Classification Criteria for Macrophage Activation Syndrome, the patient fulfilled the criteria for macrophage activation syndrome complicating systemic inflammation. ^{Reference Ravelli, Minoia and Davì15} The patient’s clinical and laboratory profile strongly suggested an underlying cytokine storm, and in this context, interferon-gamma inhibition with emapalumab was considered a rational therapeutic escalation.

In some patients, cardiac function may remain insufficient despite pharmacologic therapy, necessitating mechanical circulatory support. Options include venoarterial extracorporeal membrane oxygenation, transaortic microaxial flow pumps (Impella), intra-aortic balloon pumps, and left ventricular assist devices, with selection based on patient age, weight, and clinical status. In the paediatric population, venoarterial extracorporeal membrane oxygenation is the most commonly used modality. However, standard cannulation (aorta and right atrium) may lead to left ventricular overload, thereby increasing the risk of myocardial ischaemia, elevated left ventricle pressures, pulmonary oedema, and thrombosis. Effective left ventricular decompression is essential to promote myocardial recovery and has recently garnered increased clinical attention. ^{Reference Meani, Taccone and Veronese16,Reference Veronese, Meani and Sirico17}

Several strategies exist for decompression, including percutaneous techniques such as intra-aortic balloon pumps, atrial septostomy, or Impella, as well as surgical methods such as cannulation of the left atrium or left ventricle apex. ^{Reference Meani, Gelsomino and Natour18,Reference Ezad, Ramanathan and Donker19} In paediatric patients, percutaneous options may be limited due to small vessel size and large sheath requirements. Given the patient’s age, weight, and need for left ventricular assist device consideration, surgical decompression was chosen. Median sternotomy was performed, and three cannulas were placed in the right atrium, aorta, and left ventricle apex, respectively, to achieve effective decompression.

To date, there is no universally accepted treatment protocol for fulminant myocarditis due to the incomplete understanding of its underlying pathophysiology. Wang et al. proposed a “life support–based comprehensive treatment regimen,” which includes both medical immunoregulation and mechanical support to stabilise circulation and reduce myocardial strain, thereby improving cardiac function. ^{Reference Wang, Li and Jiang20}

In our patient, we implemented a multimodal therapeutic strategy: immunomodulatory therapy (intravenous immunoglobulin, methylprednisolone, anakinra and emapalumab), antioxidant therapy (intravenous nicotinamide adenine dinucleotide, coenzyme Q10, and quercetin), and mechanical support via venoarterial extracorporeal membrane oxygenation with direct left ventricular decompression. To the best of our knowledge, this is the first paediatric case of fulminant myocarditis treated with a life support–based comprehensive regimen incorporating emapalumab.

In conclusion, in cases of fulminant myocarditis that can have a rapid and fatal course, rapid and combined treatments with a multidisciplinary approach can be life-saving.