BACKGROUND: Performance of endomyocardial biopsy (EMB) to diagnose myocarditis in patients with dilated cardiomyopathy is controversial because of a lack of evidence favoring immunosuppressive therapy. In spite of advances in heart failure treatment, dilated cardiomyopathy carries a poor prognosis, and myocardial inflammation and viral infection are potential therapeutic targets. METHODS: We 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. Literature-based estimates included prevalence of myocarditis among patients with dilated cardiomyopathy with or without borderline myocarditis (16% and 11%, respectively); probability of 5-year transplantation-free survival (55%); sensitivity (50% and 63%, respectively), specificity (95.4%), and mortality rate (0.4%) of EMB; side effects resulting in withdrawal of immunosuppressive treatment (4%); and a 6-month mortality rate for immunosuppressive treatment (0.1%). All estimates were varied to determine impact on model results (sensitivity analysis). RESULTS: A therapy that decreased the rate of death or transplantation by 12.7% and 7.1% for patients without or with borderline myocarditis, respectively, favored EMB. 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 5790 and 380 end points, respectively. CONCLUSION: Decreasing the rate of death or transplantation by 7.1% offsets therapy side effects, EMB-related death, and inaccuracies in histologic diagnosis. Prospective randomized trials of treatments for myocarditis may be more feasible during periods of high prevalence or with more sensitive diagnostic techniques.
BACKGROUND: Performance of endomyocardial biopsy (EMB) to diagnose myocarditis in patients with dilated cardiomyopathy is controversial because of a lack of evidence favoring immunosuppressive therapy. In spite of advances in heart failure treatment, dilated cardiomyopathy carries a poor prognosis, and myocardial inflammation and viral infection are potential therapeutic targets. METHODS: We 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. Literature-based estimates included prevalence of myocarditis among patients with dilated cardiomyopathy with or without borderline myocarditis (16% and 11%, respectively); probability of 5-year transplantation-free survival (55%); sensitivity (50% and 63%, respectively), specificity (95.4%), and mortality rate (0.4%) of EMB; side effects resulting in withdrawal of immunosuppressive treatment (4%); and a 6-month mortality rate for immunosuppressive treatment (0.1%). All estimates were varied to determine impact on model results (sensitivity analysis). RESULTS: A therapy that decreased the rate of death or transplantation by 12.7% and 7.1% for patients without or with borderline myocarditis, respectively, favored EMB. 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 5790 and 380 end points, respectively. CONCLUSION: Decreasing the rate of death or transplantation by 7.1% offsets therapy side effects, EMB-related death, and inaccuracies in histologic diagnosis. Prospective randomized trials of treatments for myocarditis may be more feasible during periods of high prevalence or with more sensitive diagnostic techniques.
Authors: Bettina Heidecker; Michelle M Kittleson; Edward K Kasper; Ilan S Wittstein; Hunter C Champion; Stuart D Russell; Ralph H Hruban; E Rene Rodriguez; Kenneth L Baughman; Joshua M Hare Journal: Circulation Date: 2011-03-07 Impact factor: 29.690