Review of HHV-6 induced inflammatory cardiomyopathy in immunocompetent children

A review published in Annals of Pediatric Cardiology examines 11 previously published cases of pediatric myocarditis and subsequent dilated cardiomyopathy associated with HHV-6. Although only a small number of pediatric cases have been reported in literature, the authors conclude that evidence suggests HHV-6 should be considered as a causative agent of inflammatory cardiomyopathy, particularly in young children (under 3 years of age) who might be experiencing a primary infection.

The authors point out that given the fact that low levels of latent HHV-6 DNA can be found in healthy controls, the pathological role of HHV-6 in cases of pediatric myocarditis remains unclear. Their discussion urges the utilization of quantitative polymerase chain reaction or mRNA testing to allow differentiation between low-level latent virus found in asymptomatic myocardium and active HHV-6 infection.

The review offers several important observations:

  • 1) Seven out of 11 (64%) cases reviewed resulted in sudden death, frequently within a week of initial symptoms. This echoes similar findings from previous studies in adults, which have suggested HHV-6-associated cases of myocarditis and DCM more often have a severe clinical course resulting in death or transplantation when compared to other causes of viral myocarditis. In one previous study of 31 adult cases of viral myocarditis, patients with HHV-6 more frequently presented with new-onset acute systolic heart failure and subsequently progressed toward chronic heart failure when compared to other viral causes (coxsackie B, PVB19, EBV) (Mahrholdt 2006).
  • 2) All three distinct pathological stages of viral myocarditis were observed in the reviewed cases. 6/11 (55%) cases fell within the pathological category of “acute myocarditis,” evidenced by acute systolic heart failure and histopathological evidence of myocardial inflammation and damage. These patients all presented with the classic symptoms of HHV-6 primary infection: febrile illness and exanthema (other symptoms included tachycardia, respiratory distress, convulsions, and lymphadenopathy). 2/11 (18%) of the cases fell within the pathological category of “subacute/chronic myocarditis,” characterized by involvement of mononuclear cell infiltration and minor fibrosis. One patient demonstrated symptoms of exanthema subitum, and eventually recovered after left ventricular assist device (LVAD) support and antiviral treatment. The remaining 3/11 (27%) of cases were categorized as dilated cardiomyopathy, confirmed by echocardiograph findings of ventricular dilatation and/or histopathological evidence of endomyocardial fibrosis. This subset primarily presented with respiratory distress and arrhythmia, with no remarkable evidence of cardiac inflammation.
  • 3) Several of the patients demonstrated extra-cardiac organ involvement. Two patients had signs of central nervous system (CNS) dysfunction (including convulsions and/or status epilepticus), and two patients also demonstrated kidney and/or liver failure. As these particular extracardiac findings (i.e., CNS dysfunction, liver failure, and kidney failure) are associated with HHV-6 infection, they may provide evidence to HHV-6 being etiologically involved with the dysfunction of multiple organs.

Future studies are required to establish confirmatory diagnostic criteria for reliably determining active infection in biopsy samples, as well as deeper insights into the role of cardiotropic coinfections such as parvovirus B19.

Read the full paper: Reddy 2017