Acute myocarditis mostly does not sufficiently respond to symptomatic medication for heart failure, and mortality is high in spite of treatment. The long-term disease course depends on the pathogen, the extent and type of inflammation, and the initial injury to the myocardium. Focal borderline myocarditis often undergoes spontaneous clinical healing if no serious heart failure developed initially. The early mortality of fulminant lymphocytic myocarditis requiring intensive care is in excess of 40% in the first 4 weeks (7). Untreated giant cell and eosinophilic myocarditis also have an extremely poor prognosis, with 4 year survival rates of less than 20% (8). Granulomatous necrotizing myocarditis is lethal if overlooked and untreated. Non-fulminant active myocarditis has a mortality rate of 25% to 56% within 3 to 10 years, owing to progressive heart failure and sudden cardiac death, especially if symptomatic heart failure manifests early on (9– 11, e1). In addition to impaired left ventricular (LV) and right ventricular (RV) function, virus persistence, chronic inflammation, and cardiodepressive autoantibodies are independent predictors of a poor prognosis (9, 12, 13).
Background and methods
Myocarditis and inflammatory cardiomyopathies can be caused by infections, drugs, toxic substances, and autoimmune diseases. We present their clinical features, diagnostic evaluation, treatment, and prognosis on the basis of a selective review of the literature, current expert opinion, and our own clinical experience.
The pathological mechanisms that are accessible to treatment lie at the cellular and molecular levels and generally give rise to nonspecific disease manifestations. Specific treatment is possible only on the basis of a standardized diagnostic evaluation of a biopsy specimen, rather than clinical examination alone. Therapeutic decisions must be based on the results of thorough myocardial biopsy studies while taking account of the individual patient’s clinical course. Moreover, treatment can help only if a treatable cause is present (e.g., a viral infection, an inflammatory process, or cardiodepressive antibodies), and only if the myocardium still has regenerative potential. Once irreversible myocardial injury has occurred—for example, if the diagnosis of post-infectious or post-inflammatory dilated cardiomyopathy has been missed until it is too late—then the development or progression of heart failure in the long term can no longer be prevented.
Recent studies have shown that specific treatment can help patients with viral, inflammatory, or autoimmune cardiomyopathy that has been precisely characterized by means of a myocardial biopsy. More randomized trials with larger patient cohorts are needed for further optimization of treatment.
The term myocarditis describes inflammatory disorders of the heart muscle of varied infectious and non-infectious origin (Box). In acute myocarditis, infectious strains usually cause myocardial inflammation with subsequent disturbance of left ventricular or right ventricular function. In Western industrialized countries these pathogens are primarily viruses, whereas in developing countries the cause may be bacterial, protozoal, or fungal infections. Myocardial processes triggered by infectious and non-infectious causes also underlie the chronic-inflammatory myocardial disorders (Figure 1). If the immune system does not eliminate the infectious pathogen early on—owing to insufficient activation, e.g. on the basis of a genetic predisposition—chronic infection develops, which may or may not be accompanied by inflammation (1). If the inflammatory response does not spontaneously resolve after successful elimination of the pathogen, chronic-inflammatory cardiomyopathy is present (Figure 1) (2). In addition to such postinfectious inflammatory processes, accompanying cellular or humoral inflammations in systemic diseases may cause lasting injury to the myocardium.