What virus is most commonly associated with dilated cardiomyopathy in adults?

Viruses That Cause Dilated Cardiomyopathy

In adults, parvovirus B19 and human herpes virus 6 are now the most frequently identified viruses in chronic dilated cardiomyopathy in Western Europe, while enteroviruses (particularly Coxsackievirus B) remain important in North America. 1

Primary Viral Etiologies by Age Group

Adults

• Parvovirus B19 and human herpes virus 6 are the predominant viruses detected in chronic cases in Western Europe 1
• Enteroviruses, particularly Coxsackievirus B (especially types B2 and B3), remain the major cardiotropic viruses in North America 1, 2
• Coxsackievirus B3 shows the greatest nucleotide sequence homology in myocardial tissue from patients with end-stage dilated cardiomyopathy 2
• Other identified viruses include adenoviruses, cytomegalovirus, Epstein-Barr virus, influenza, respiratory syncytial virus, herpes simplex virus, human herpesvirus 6, HIV, and hepatitis C 3
• Viral genomes are detected in 40% of myocarditis/DCM samples, with adenovirus and enterovirus being most frequent 3

Children

• Enteroviruses (including Coxsackievirus), adenoviruses, and parvovirus B19 are the most common causes 3
• The viral landscape has evolved over decades: Coxsackievirus predominated in the 1980s-1990s, followed by adenovirus in the 1990s, now replaced by parvovirus B19 3
• Adenovirus carries the worst prognosis in children, with only 66% 5-year survival in children under 1 year with adenovirus-positive myocarditis versus 95% in PCR-negative patients 3

Pathophysiologic Mechanisms

Viral Persistence

• Viral persistence after acute infection is the most common pathway to chronic myocarditis and dilated cardiomyopathy in developed countries 1
• Viral genomes remain detectable in myocardial tissue despite clearance of active viremia, serving as a continuous source of antigen to stimulate immune responses 4, 1
• Enterovirus persistence involves 5' terminal genomic RNA deletions (17-50 nucleotides) that allow early replication without detectable viral plaque formation 5
• These persistent viral forms produce proteolytically active viral proteinase 2A that impairs cardiomyocyte function 5

Coinfection

• Coinfection with two or more viruses occurs in a substantial minority and may predispose to chronicity 1

Diagnostic Considerations

Molecular Detection

• PCR analysis can detect fewer than 10 gene copies of viral pathogens in myocardium 3
• Enterovirus RNA is detected in 56% of patients with histologically proven myocarditis or dilated cardiomyopathy 6
• Multiple biopsies increase detection rates to 75%, indicating the focal nature of the disease 6
• Critical caveat: A negative PCR does not exclude viral disease due to sampling error and uncertain sensitivity 3

Serological Testing

• Enterovirus-specific IgM responses are detected in 56% of dilated cardiomyopathy patients versus 28% of controls 2
• However, the high background prevalence limits diagnostic value 2
• For herpes simplex virus, a four-fold rise in antibody titers is suggestive but not diagnostic (Class IIb indication) 4

Histopathology

• Coxsackievirus consistently shows classic frank myocarditis histologically 3
• Adenovirus most commonly shows borderline myocarditis features 3
• Parvovirus, Epstein-Barr virus, and cytomegalovirus have variable histological features 3

Clinical Implications

Prognosis

• Children with viral cardiomyopathy have superior survival compared to idiopathic DCM 3
• Adenovirus serotypes 3 and 7 carry particularly poor prognosis 7
• Chronic inflammation leads to progressive collagen deposition (mean 14% collagen volume fraction) and irreversible myocardial fibrosis 1

Geographic Variations

• Coxsackievirus B2 is predominant (55.9-60.2%) in cardiology patients in certain regions 8
• Chagas disease (Trypanosoma cruzi) is a major cause in Central and South America, with one-third of seropositive individuals developing chronic cardiac disease 1