Risk stratification at diagnosis for children with hypertrophic cardiomyopathy: an analysis of data from the Pediatric Cardiomyopathy Registry

Summary

Background

Treatment of children with hypertrophic cardiomyopathy might be improved if the risk of death or heart transplantation could be predicted by risk factors present at the time of diagnosis.

Methods

We analysed data from the Pediatric Cardiomyopathy Registry, which collected longitudinal data for 1085 children with hypertrophic cardiomyopathy from 1990 to 2009. Our goal was to understand how patient factors measured at diagnosis predicted the subsequent risk of the primary outcome of death or heart transplantation. The Kaplan-Meier method was used to calculate time-to-event rates from time of diagnosis to the earlier of heart transplantation or death for children in each subgroup. Cox proportional-hazards regression was used to identify univariable and multivariable predictors of death or heart transplantation within each causal subgroup.

Findings

The poorest outcomes were recorded for the 69 children with pure hypertrophic cardiomyopathy with inborn errors of metabolism, for whom the estimated rate of death or heart transplantation was 57% (95% CI 44–69) at 2 years. Children with mixed functional phenotypes also did poorly, with rates of death or heart transplantation of 45% (95% CI 32–58) at 2 years for the 69 children with mixed hypertrophic and dilated cardiomyopathy and 38% (95% CI 25–51) at 2 years for the 58 children with mixed hypertrophic and restrictive cardiomyopathy. For children diagnosed with hypertrophic cardiomyopathy at younger than 1 year, the rate of death or transplantation was 21% (95% CI 16–27) at 2 years. For children diagnosed with hypertrophic cardiomyopathy and a malformation syndrome, the rate of death or transplantation was 23% (95% CI 12–34) at 2 years. Excellent outcomes were reported for the 407 children who were diagnosed with idiopathic hypertrophic cardiomyopathy at age 1 year or older, with a rate of death or heart transplantation of 3% (95% CI 1–5) at 2 years. The risk factors for poor outcomes varied according to hypertrophic cardiomyopathy subgroup, but they generally included young age, low weight, presence of congestive heart failure, lower left ventricular fractional shortening, or higher left ventricular end-diastolic posterior wall thickness or end-diastolic ventricular septal thickness at the time of cardiomyopathy diagnosis. For all hypertrophic cardiomyopathy subgroups, the risk of death or heart transplantation was significantly increased when two or more risk factors were present and also as the number of risk factors increased.

Interpretation

In children with hypertrophic cardiomyopathy, the risk of death or heart transplantation was greatest for those who presented as infants or with inborn errors of metabolism or with mixed hypertrophic and dilated or restrictive cardiomyopathy. Risk stratification by subgroup of cardiomyopathy, by characteristics such as low weight, congestive heart failure, or abnormal echocardiographic findings, and by the presence of multiple risk factors allows for more informed clinical decision making and prognosis at the time of diagnosis.

Funding

US National Institutes of Health and Children's Cardiomyopathy Foundation.

Introduction

Cardiomyopathy is a rare but serious condition in infants and children. Hypertrophic cardiomyopathy is a heterogeneous group of disorders in childhood.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 Paediatric hypertrophic cardiomyopathy encompasses conditions with diverse genetic origins and clinical phenotypes, including associations with inborn errors of metabolism, neuromuscular disorders, and malformation syndromes.7, 11 Few data are available to predict which patients with paediatric hypertrophic cardiomyopathy will progress to end-stage pump failure with subsequent death or need for heart transplantation or who will die from sudden cardiac death.12, 13, 14 Despite the relative rarity of this disorder, the incidence, morbidity, and mortality are higher in the first year of life by a factor of ten compared with the rest of childhood.9, 10, 12 Increased understanding of the factors contributing to a poor outcome in the various causal subgroups of paediatric hypertrophic cardiomyopathy is needed.

Using data from the Pediatric Cardiomyopathy Registry (PCMR) funded by the National Heart, Lung, and Blood Institute of the US National Institutes of Health, we have previously reported the demographic and clinical features of children with pure hypertrophic cardiomyopathy, as well as their clinical outcomes.¹² In that report, all available annual follow-up data were used to categorise children into causal subgroups in as scientifically rigorous a manner as possible. Clinical outcome and survival were found to be dependent on the cause of hypertrophic cardiomyopathy and patient age. Although this report provided the most complete estimates of the causes of the disease, the effect of clinical characteristics at the time of diagnosis on outcome was not evaluated. Physicians treating children with hypertrophic cardiomyopathy must base their initial course of care on information collected at the time of diagnosis. Therefore, we have reanalysed the PCMR database to quantify clinical outcomes and their predictors on the basis of causal subgroups (including age at diagnosis and mixed phenotype hypertrophic cardiomyopathy) in children with hypertrophic cardiomyopathy at the time of diagnosis. Our goal was to understand how patient factors measured at the time of diagnosis will predict the subsequent risk of death or heart transplantation. Our hope is that this information will allow clinicians to more effectively stratify patients by risk, to improve family counselling and clinical planning development for these children, resulting in reduced morbidity and mortality.