What causes chronic myocarditis?

Causes of Chronic Myocarditis

Chronic myocarditis develops when persistent viral infection, ongoing autoimmune inflammation, or secondary immune responses continue beyond the acute phase, leading to sustained myocardial inflammation with progressive fibrosis and heart failure. 1

Primary Etiologic Mechanisms

Persistent Viral Infection

• Viral persistence after acute infection is the most common pathway to chronic myocarditis in developed countries, with viral genomes detectable in myocardial tissue despite clearance of active viremia 1, 2
• Parvovirus B19 and human herpes virus 6 are the most frequently identified viruses in chronic cases in Western Europe, while enteroviruses (particularly Coxsackie B) remain important in North America 1
• The virus cannot be fully eliminated by the immune system, creating ongoing low-grade inflammation that transitions from acute to chronic disease 3
• Coinfection with two or more viruses occurs in a substantial minority and may predispose to chronicity 1

Post-Infectious Autoimmunity

• Autoimmune mechanisms can persist even after successful viral clearance, representing a secondary immune response that becomes self-perpetuating 1, 2
• The initial viral infection triggers immune responses that subsequently target cardiac self-antigens, creating chronic inflammation independent of ongoing infection 4
• This autoimmune pathway explains why some patients develop chronic symptoms despite no detectable viral genome on endomyocardial biopsy 3

Specific Chronic Myocarditis Subtypes

Cardiac Sarcoidosis

• Cardiac sarcoidosis frequently presents as chronic myocarditis and often affects the heart without clinical evidence of extracardiac disease 1
• Noncaseating granulomas cause ongoing inflammation, though their absence on biopsy does not exclude the diagnosis 1
• This represents a distinct autoimmune/inflammatory pathway to chronic myocardial disease 5

Giant Cell Myocarditis

• Giant cell myocarditis is an aggressive autoimmune disorder that, if untreated acutely, can transition to chronic disease requiring ongoing immunosuppression 1, 6
• This subtype is rapidly fatal without multidrug immunosuppression and advanced heart failure management 1, 6
• Unlike typical viral myocarditis, this represents primary autoimmune pathology rather than post-infectious sequelae 4

Eosinophilic Myocarditis

• Caused by hypersensitivity reactions, drug sensitivity, neoplasia, vasculitis, or hematologic disorders that create sustained eosinophilic infiltration 1
• The chronic exposure to the inciting agent (often medications) perpetuates inflammation 1

Systemic Autoimmune Disease-Associated Myocarditis

• Rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis cause chronic myocardial inflammation as part of systemic autoimmune processes 1
• In rheumatoid arthritis, 46-55% of patients show focal late gadolinium enhancement on cardiac MRI, indicating chronic myocardial injury 1
• In systemic sclerosis, 17-53% demonstrate chronic myocardial involvement with fibrosis 1
• These represent ongoing autoimmune attacks on myocardial tissue driven by systemic disease activity 7

Pathophysiologic Progression to Chronicity

Failed Immune Down-Regulation

• In most acute myocarditis cases, the immune reaction is eventually down-regulated and myocardium recovers 8
• In chronic cases, persistent myocardial inflammation leads to ongoing myocyte damage and relentless symptomatic heart failure 8
• The transition occurs when inflammatory events survive successful clearance of initial cardiotoxic agents or are amplified by autoimmunological processes 2

Fibrotic Remodeling

• Chronic inflammation leads to progressive collagen deposition, with chronic myocarditis patients showing mean collagen volume fraction of 14% 1
• Late gadolinium enhancement is seen in up to 70% of patients with biopsy-proven chronic inflammation in the setting of heart failure 1
• This fibrosis represents irreversible myocardial damage from sustained inflammation 1

Geographic and Exposure-Specific Causes

Endemic Infectious Causes

• Chagas disease (Trypanosoma cruzi) is a major cause of chronic myocarditis in Central and South America, with one-third of seropositive individuals developing chronic cardiac disease 1
• HIV causes chronic cardiomyopathy in 8% of asymptomatic individuals through persistent viral effects 1
• These represent ongoing parasitic or viral presence creating sustained myocardial injury 1

Clinical Pitfalls

The key distinction is that chronic myocarditis requires either persistent infectious agent, ongoing autoimmune inflammation, or post-infectious autoimmunity—not simply prolonged symptoms from acute injury. 2, 3 Accurate diagnosis demands endomyocardial biopsy with simultaneous histologic, immunohistochemical, and molecular biological workup to distinguish active infection from autoimmune inflammation. 3 Clinical methods and imaging alone are misleading when infectious agents are involved. 3