Journal Information
Vol. 97. Issue 5.
Pages 354-356 (01 November 2022)
Vol. 97. Issue 5.
Pages 354-356 (01 November 2022)
Scientific Letter
Open Access
Coxsackievirus-induced myocarditis
Miocarditis agudas por virus coxsackie
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Roger Esmel-Vilomaraa,b,
Corresponding author
roger.esmel@gmail.com

Corresponding author.
, Paola Doladerb, Gemma Giraltb, Queralt Ferrerb, Ferran Granb
a Cardiología Pediátrica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
b Cardiología Pediátrica, Vall d’Hebron Hospital Campus, Barcelona, Spain
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Dear Editor:

Acute myocarditis is a life-threatening myocardial inflammatory disease mainly caused by viral infections. Virus-induced myocarditis can refer to virus-mediated or virus-triggered (immune-mediated) disease; coxsackieviruses may cause virus-mediated myocarditis, as viral replication can cause direct cardiomyocyte injury.1

There are critical knowledge gaps regarding the diagnosis, prognosis and treatment of myocarditis. The aim of this report is to describe the clinical presentation of coxsackievirus-induced myocarditis and its outcomes.

Coxsackievirus is one of the most common causative agents of myocarditis in children. In a period of 14 years (April 2007 to September 2021), there were 5 cases of coxsackievirus-induced myocarditis confirmed by polymerase chain reaction (PCR) testing of blood samples out of 55 cases of viral myocarditis, making coxsackievirus the second leading causative agent in the sample following parvovirus B19.

The cases occurred in 4 newborns (median age 16.5 days, range 8–24) and 1 infant aged 10-months. Table 1 presents the demographic and clinical characteristics of the sample.

Table 1.

Clinical presentation and followup of the patients.

PatientAgeSexInitial clinical presentationInitial ejection fraction (Echo)Cardiovascular magnetic resonance imagingPositive PCRSpecific treatmentOutcomeDays to cardiac function recovery
Lake-Louise criteriaPericardial effusion
T2-weighted images  Early gadolinium enhancement (T1)  Late gadolinium enhancement (T1) 
24 days  Male  Cardiogenic shock  29%  High signal intensity  Not performed  Not assessable  Absent  Blood    Complete recovery  65 
24 days  Male  Cardiogenic shock  30%  High signal intensity  Negative  Positive  Absent  Blood    Complete recovery  58 
9 days  Male  Cardiogenic shock  42%  Negative  Positive  Not assessable  Present  Blood and CSF    Complete recovery  168 
10 months  Male  Heart failure  45%  High signal intensity  Positive  Negative  Absent  Blood and TA    Complete recovery 
8 days  Female  Cardiogenic shock  15%          Blood  Interferon beta + corticosteroids  Complete recovery  147 

CSF, cerebrospinal fluid; Echo, echocardiography; PCR, polymerase chain reaction; TA, tracheal aspirate.

Certain Enterovirus serotypes are associated with particular clinical phenotypes and age groups.2 In the subset of cases of Enterovirus infection in our sample, coxsackievirus was the only detected virus, as it is the predominant type causing myocarditis.3 Four fifths of the patients with coxsackievirus were newborns, and other viruses were found in older children. As previously described, Enterovirus myocarditis and sepsis affect significantly younger children compared to other presentations.2 A systematic review of severe neonatal enterovirus infections found that 54.7% of the cases of myocarditis occurred in newborns aged less than 7 days.3 Coxsackievirus–adenovirus-receptor (CAR) is a key element of coxsackievirus-induced myocarditis that also plays a role in cardiac morphogenesis. Its expression peaks in the perinatal period, after which levels decrease with age, thereby decreasing the risk of fatal myocarditis.4

The infection may be transmitted vertically, before or after delivery, or horizontally.3 All cases in our sample involved horizontal transmission, with a history of upper respiratory tract infection preceding heart dysfunction by a median of 4 days (range, 1–7), although the tracheal aspirate PCR test was only positive in 1 patient. While it has been reported that PCR cycle threshold values are considerably lower in faecal samples compared to blood,2 routine faecal PCR testing in neonates with myocarditis may identify the etiological agent efficiently.

All newborns presented with severe disease in the form of cardiogenic shock, which was consistent with previous studies2,3 and could be explained by their functionally immature immune system3 and upregulated expression of CAR in the perinatal period.4 The infant presented with heart failure. None of the patients had arrhythmia. All patients required admission to the intensive care unit and inotropic support, and all but one (80%) mechanical ventilation. On the other hand, adults usually develop mild symptoms, with only 8.6% presenting with fulminant myocarditis in a retrospective registry.1

Electrocardiographic abnormalities were present in 3 patients: ventricular repolarization abnormalities (2/5, 40%) and q waves (2/5, 40%). The initial blood tests showed elevated levels of troponin and creatine kinase. The echocardiographic assessment revealed left ventricular (LV) dysfunction in every patient (median ejection fraction, 30%; IQR, 13%), LV dilatation in 1, left atrial dilatation in 4 and mitral valve regurgitation in 4. Left ventricular hypertrophy was present in 4 patients (80%). Significant right ventricular dysfunction was present in 2 patients.

The clinical diagnosis of myocarditis was confirmed in all but one patient by cardiovascular magnetic resonance imaging (CMR), the primary tool for non-invasive assessment of myocardial inflammation.5Table 1 documents the Lake-Louise criteria and the presence of pericardial effusion. The patient that did not undergo CMR in the acute phase presented with cardiogenic shock almost requiring mechanical circulatory support, and coronary involvement was ruled out in the catheterization laboratory. She remained haemodynamically unstable and required inotropic support for 39 days, and was therefore unable to be transported to undergo CMR. Ideally, CMR should be performed within 2–3 weeks of the onset of symptoms.1

The previous literature describes a substantial neonatal mortality, of up to 38.6%, in addition to persistent of impaired myocardial function in a large proportion of survivors.2,3 In contrast, we found complete recovery of cardiac function in 100% of patients in a median of 65 days (IQR, 89).

Per our protocol, implemented since 2015, corticosteroids and interferon beta (IFNß) are administered to patients with severe Enterovirus myocarditis (need for extracorporeal membrane oxygenation or severe dysfunction without improvement after 2 weeks). Recent research supports the role of IFNß in effective enterovirus clearance, LV function improvement and survival,6 as viral replication causes direct cardiomyocyte injury in virus-mediated myocarditis.1 Our most unstable patient received IFNß leading to successful recovery. Furthermore, immunosuppressive therapy has been proposed if myocardial damage is associated with lymphocytic infiltration,1 so steroids may also be useful.

In conclusion, in this sample of patients with myocarditis confirmed by CMR, we found a severe clinical presentation, and we believe that newborns presenting with cardiogenic shock should be tested for coxsackievirus. In contrast to previous series, outcomes in our sample were favourable, as 100% of patients survived and achieve complete cardiac recovery. The administration of IFNß and steroids could be useful to improve outcomes, although further multicentre studies are needed.

Acknowledgement

Authors have no relevant financial or non-financial interests to disclose. No funds, grants, or other support was received.

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Management of acute myocarditis and chronic inflammatory cardiomyopathy: an expert consensus document.
[2]
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Severe enterovirus infections in hospitalized children in the south of England: clinical phenotypes and causative genotypes.
Pediatr Infect Dis J., 35 (2016), pp. 723-727
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Clinical characteristics of severe neonatal enterovirus infection: a systematic review.
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CAR-diology - a virus receptor in the healthy and diseased heart.
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International Consensus Group on Cardiovascular Magnetic Resonance in Myocarditis. Cardiovascular magnetic resonance in myocarditis: a JACC white paper.
J Am Coll Cardiol., 53 (2009), pp. 1475-1487
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Interferon-beta improves survival in enterovirus-associated cardiomyopathy.
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