Making Decisions About Endomyocardial Biopsy In Myocarditis

Most patients with dilated cardiomyopathy who have endomyocardial biopsy do not have any change in their clinical therapy as a result of the biopsy. About 80% to 90% of patients who have endomyocardial biopsy either because of new-onset heart failure or because of clinically suspected myocarditis have the nonspecific histologic finding of myocyte hypertrophy and fibrosis. About 10% to 20% of endomyocardial biopsies give definitive information for a specific diagnosis such as myocarditis, amyloidosis, sarcoidosis, or hemochromatosis. In less than half of the patients in whom a specific diagnosis is made, there is a change in clinical treatment based solely on the endomyocardial biopsy result.

The decision to proceed with an endomyocardial biopsy in a patient with suspected myocarditis should balance the expected gain from an accurate diagnosis with its attendant therapeutic implications against the small risk of a major procedural complication. Most patients with clinically suspected myocarditis do not have biopsy-proven myocarditis, and thus immunosuppressive therapy based solely on a clinical diagnosis of myocarditis is unwise. The Clinical Trial of Immunosuppressive Therapy for Myocarditis did not show a beneficial effect of immunosuppressive therapy (prednisone with either cyclosporine or azathioprine) on left ventricular function at 28 weeks in patients with biopsy-proven active myocarditis. The conclusion of this study does not apply to patients with other forms of histologically proven myocarditis that were not studied, including giant cell myocarditis, peripartum myocarditis, hypersensitivity myocarditis, and cardiac sarcoidosis.

ESETCID addresses some of the problems encountered in the Clinical Trial of Immunosuppressive Therapy for Myocarditis by distinguishing between different forms of myocarditis. Patients with cytomegalovirus-induced myocarditis will be treated by hyper-immunoglobulin or placebo. Patients with enterovirus-positive myocarditis will receive interferon-alfa or placebo. Patients with virus-negative myocarditis, which is considered autoimmune, will be treated with immunosuppression or placebo. The primary end point of this study will be an improvement in ejection fraction of more than 5%.

Hrobon et al.28 used decision analysis to determine the efficacy (5-year risk reduction in mortality or transplantation) that a treatment for myocarditis would require to favor a biopsy-guided approach over conventional therapy. The prevalence of myocarditis among patients with dilated cardiomyopathy was estimated from the published literature (including or excluding borderline myocarditis) as 16% and 11%, respectively; sensitivity of endomyocardial biopsy diagnosis of myocarditis, 63% and 50%, respectively; probability of 5-year transplantation-free survival, 55%; specificity of endomyocardial biopsy diagnosis, 95.4%; mortality rate of endomyocardial biopsy, 0.4%; side effects resulting in withdrawal of immunosuppressive treatment, 4%; and 6-month mortality rate for immunosuppressive treatment, 0.1%.

The authors concluded that a therapy that decreased the rate of death or transplantation by 12.7% and 7.1% for patients, excluding or including borderline myocarditis, respectively, favored endomyocardial biopsy. Sensitivity analysis indicated that therapeutic efficacy was influenced by myocarditis prevalence and biopsy-related death but not by accuracy of biopsy or probability of immunosuppressive therapy side effects. Randomized trials powered to detect 7% and 25% reductions in death and transplantation would require 5,790 and 380 end points, respectively. Decreasing the rate of death or transplantation by 7.1% offsets therapy side effects, endomyocardial biopsy-related death, and inaccuracies in histologic diagnosis. Variables in this decision analysis that significantly affected outcome included the prevalence of myocarditis and the sensitivity of the diagnostic techniques.

The initial therapy for patients with suspected myocarditis is hospital admission for bed rest and electrocardiogram monitoring and vasodilators to decrease vascular resistance and lower left ventricular filling pressures. Patients with acute fulminant myocarditis and hemodynamic deterioration may benefit from short-term circulatory support with left ventricular-assist devices. The rationale for this approach is that short-term left ventricular support reduces wall stress and allows time for improvement in myocyte function.

Immunosuppressive therapy is not recommended in patients with acute infectious or postinfectious myocarditis, but a small subset of patients with noninfectious myocarditis due to giant cell myocarditis, scleroderma, lupus erythematosus, polymyositis, or sarcoidosis may benefit from immunosuppressive therapy.

A beneficial treatment of inflammatory heart disease is still difficult and not yet validated by a study with patient numbers sufficient to allow statistical analysis. The ESETCID addresses problems of etiology, pathogenesis, and specific treatment of myocarditis. It is the first multicenter, double-blind placebo-controlled randomized study, apart from the Myocarditis Treatment Trial, to distinguish between different forms of myocarditis. In the ESETCID, patients with acute or chronic myocarditis are treated specifically according to the etiology of the disease. This trial may yield a better understanding of the course of myocarditis, leading to more specific treatment, which may in turn decrease the number of patients with post-myocardial infarction heart muscle disease who require heart transplantation as a final therapeutic remedy.

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