We appreciate Dr. Guntheroth’s remarks regarding our retrospective observational study (1) on pediatric dilated cardiomyopathy (DCM). His concerns appropriately point out the limitation of all observational studies—that one can never tell what would have happened to the treated group (in this case those who were transplanted) had they not undergone treatment because there is no valid comparison group. However, 75% of the patients transplanted in our study were on persistent inotropic support (UNOS status 1) at the time of transplant and had failed attempts to remove inotropic support. Data from the Pediatric Heart Transplant Study (PHTS) (2) suggest that inotropic support is a risk factor for death before transplant. Thus, we believe our patients who underwent transplantation represented a substantially sicker subgroup of patients within the patient population studied. However, newer heart failure therapies such as beta-blockade have been reported to remove the survival advantage from heart transplantation in adults (3) and to decrease utilization of heart transplantation in infants and children (4). The role of heart transplantation as therapy for pediatric DCM needs to be continually redefined as newer heart failure therapies are applied to pediatric heart disease.

Dr. Guntheroth suggests that inclusion of patients with DCM from metabolic disease or muscular dystrophy may be misleading because of the uniformly fatal nature of those diseases. The differing natural history of the Becker and Duchenne variants of dystrophin muscular dystrophy underscores the difficulties of lumping all metabolic cardiomyopathies and muscular dystrophies in one common prognostic group.

We would agree with Dr. Guntheroth that the criteria used in our study to diagnose myocarditis are not clear cut. The frequency of viral infection in children can make it likely that any diagnosis of a DCM can generally correlate with a “recent” viral infection. Pathologic criteria can also be confusing given the patchy nature of myocardial inflammation leading to false negative endomyocardial biopsies and the presence of viral genome in myocardial samples without evidence of inflammation (5). Thus, any clear-cut definition of myocarditis in children remains difficult.