965Increased heart rate is independently associated with worse survival in pediatric patients with dilated cardiomyopathy: a multicenter study from the pediatric cardiomyopathy registry

Abstract

Background: Among adult heart failure (HF) patients, elevated heart rates are associated with an increased risk of adverse outcomes including overall mortality, cardiovascular death, and HF hospitalizations. There are few data on the association of heart rate and outcomes in HF pediatric patients. Purpose: We aimed to test the hypothesis that increased heart rate is associated with an increased risk of death and transplant in pediatric dilated cardiomyopathy (DCM) patients. Methods: The Pediatric Cardiomyopathy Registry, a large prospective registry of pediatric cardiomyopathy patients in North America, was analyzed for patients enrolled with the diagnosis of DCM from 1994-2011. Patients with a diagnosis of myocarditis, neuromuscular disease, mixed cardiomyopathy, and malformation syndromes were excluded. Heart rates were recorded at the time of study entry. Increased heart rate was defined as being ≥2 standard deviations of the mean normal value based on age. Results: 557 patients, 282 (51%) male, met enrollment criteria. Median age was 1.3 [interquartile range (IQR) 0.3, 9.8] years and median follow-up time of 1.8 years (IQR, 0.3 to 5.1 years). Increased heart rate was present in 192 (34%). Patients with an increased heart rate were older (median age 2.3 years, IQR 0.6,11.6 vs 0.9 years, IQR 0.2, 8.4; p<0.001), having HF symptoms (83% vs 67%; p<0.001), having worse ventricular function (median fractional shortening z-score -9.7, IQR -11.5, -7.5 vs -9.1, IQR -11.3, -6.2; p=0.02), and more likely to be receiving anticongestive therapies (96% vs 86%; p<0.001) and antiarrhythmic medications (31% vs 21%; p=0.008) compared to patients with normal heart rate. Beta-adrenergic blockers usage was similar in both groups (17% vs 14%; p=0.4). Survival analysis demonstrated that patients with an increased heart rate at study entry had higher mortality and lower transplant-free survival compared to patients with normal heart rate (p<0.01 for both) (Figure). On multivariable analysis controlling for age, ventricular function, and cardiac medications, the presence of an increased heart rate was independently associated with death (adjusted hazard ratio HR=2.6; IQR 1.55, 4.36; p<0.001) and death or transplant (adjusted HR 1.5; IQR 1.1, 2.1; p=0.01). Competing risk analyses showed results that are comparable to the Cox regressions. (Figure Presented) Conclusions: In this observational study, an increased heart rate was present in one third of pediatric DCM patients at the time of study entry. Elevated heart rate was associated with a greater risk of death, and of death or cardiac transplantation, independently from baseline ventricular function, medication usage, and age. Further study is needed to assess the association of elevated heart rate and disease severity in children with DCM and as potential target of therapy in pediatric DCM patients.