The PCMR enrolled 920 children with cardiomyopathy diagnosed between 1990 and 1995, of which of 350 had pure idiopathic IDC or familial isolated IDC (). Echocardiographic findings from the month of presentation were consistent with IDC. Use of selected medications in this patient group was compared to that in a group of 219 children with pure IDC diagnosed between 2000 and 2006 for whom medication data, other than anti-heart failure therapy, was collected. Anti-heart failure therapy data for children diagnosed between 2000 and 2006 were collected for all IDC cases (N=462) in the prospective cohort. All results below are based on the earlier cohort diagnosed between 1990 and 1995, unless otherwise noted.
Demographic Characteristics and Clinical Status at Presentation of 350 Children with Idiopathic Dilated Cardiomyopathy Diagnosed between 1990 and 1995
Practice variation by center was examined using the eight largest centers in terms of number of IDC cases (range, 15 to 58 per center). After accounting for differences in disease severity (left ventricular fractional shortening Z-score) in the center populations, center-specific rates of anti-heart failure therapeutic use were similar (P=0.07). However, ACEI use differed significantly among centers, with center-specific rates ranging from 46% to 89%. Anti-arrhythmic use also varied significantly, with center-specific rates ranging from 13% to 54%, as did carnitine supplementation (4% to 48%). Differences by center persisted for ACEI use (P=0.04), anti-arrhythmic use (P=0.01), and carnitine supplementation (P=0.007), even after adjustment for fractional shortening Z-score.
Anti-heart failure therapy at diagnosis was the most commonly reported intervention for all children, being reported in 84% (). Anti-heart failure administration differed by functional class (), being administered to 60% of asymptomatic (Class I) children and to 93% of children in Class II or higher (P<0.001). Anti-heart failure agents were also prescribed more frequently in children with echocardiographic evidence of more advanced HF (). Multivariate modeling (N=272) indicated that HF (odds ratio, 6.5, 95% confidence interval 3.0 to 14.0, P<0.001) and left ventricular fractional shortening Z-score (odds ratio, 0.8, 95% confidence interval 0.7 to 0.9, P<0.001) were independently associated with anti-heart failure use. Anti-heart failure therapy use was similar in the earlier and later cohorts (84% and 87%, respectively).
Initial Management of 350 Children with Idiopathic Cardiomyopathy (All rates are for children diagnosed between n 1990 and 1995, unless otherwise noted)
Figure 1 Anti-heart failure and ACE inhibitor use by functional class at diagnosis in 350 children with idiopathic dilated cardiomyopathy. (P <0.001 for the association between each therapy and functional class). See footnote for definition of (more ...)
Left Ventricular Echocardiographic Z-Scores in 350 Children with and without Anti-heart failure and ACE Inhibition Therapy at Diagnosis of Cardiomyopathy (1990-1995)
The second most frequently reported therapy, ACEI, was prescribed for 66% of children during the first month of diagnosis and for 74% within the first year. At presentation, ACEI administration was more common (P<0.001) in children with more advanced HF, as evidenced by larger left ventricular dimension and lower fractional shortening Z-scores () and in those with a worse functional class, where 77% of those in Class IV received an ACEI (). Multivariate modeling (N=249) indicated that left ventricular end-diastolic dimension Z-score (odds ratio, 1.3; 95% confidence interval, 1.1 to 1.4, P<0.001) was independently correlated with of ACEI use.
Beta-adrenergic blockade was generally not employed in the earlier cohort, being prescribed for 4% of IDC cases at presentation and 6% within the first year. The rate of ACEI administration at diagnosis did not change significantly over the 6-year (1990 to 1995) diagnostic period (65% vs. 69%). In contrast, beta-adrenergic blockade use was higher in the later cohort (18%). This difference may be the result, in part, of the fact that some children in the later cohort from several PCMR centers were enrolled in a clinical trial of a beta-blocker.18
Dietary modification (mainly salt restriction) was infrequently reported (14%), but nevertheless was associated with functional class (P=0.01), being used in 5% of Class I children and in 14% to 19% of symptomatic (Class II through IV) children. Carnitine supplementation was prescribed in 18%. As noted earlier, use of this therapy varied by center.
Calcium channel blockers (2%) and pacemakers or automatic implanted cardiac defibrillators (1%) were generally not used as initial therapy. Mechanical support was instituted in 17 children (5%) in the first 30 days after presentation. Mechanical support was provided using extracorporeal membrane oxygenation in 8 children, intra-aortic balloon pumps in 6, and ventricular assist devices in 3. Within a month after diagnosis, 17 children (5%) underwent cardiac transplantation.
The PCMR specifically recorded the medical and surgical interventions as discussed above and as illustrated in . Medical records were further scrutinized for other medications. A majority (52%) of children received a variety of other medications during treatment of their cardiomyopathy (). Anti-thrombotic agents were prescribed to 16% of the overall sample. Warfarin was the most widely used anticoagulant (9%), followed by aspirin and unfractionated heparin. Children treated with either warfarin or heparin were older at diagnosis (median 9.5 vs. 1.2 years) and more often had HF (91% vs.71%, P=0.003). However, anti-thrombotic use was independent of left ventricular size and function.
Figure 2 Miscellaneous medical and surgical therapy reported for early treatment of idiopathic dilated cardiomyopathy in 350 children. PDE = phosphodiesterase; IVIG = intravenous immunoglobulin; ECMO = extracorporeal membrane oxygenation; IABP = intra-aortic balloon (more ...)
Children treated with intravenous inotropic infusions at presentation (16%) were more symptomatic than those not receiving them (HF was present in 86% vs. 71%, P<0.001). However, as was the case with anti-thrombotic use, children treated and those not treated with inotropic infusions did not differ with regard to their echocardiographic profiles. Immunomodulatory treatment was recorded in 5% of children and was reported as intravenous immunoglobulins, glucocorticoids, or both, in nearly equal proportions ().