Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy

Abstract

Aims Childhood-onset hypertrophic cardiomyopathy (HCM) is far less common than adult-onset disease, thus natural history is not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM. Methods and results We performed an observational cohort study of 7677 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Hypertrophic cardiomyopathy patients were stratified by age at diagnosis [<1 year (infancy), 1–18 years (childhood), >18 years (adulthood)] and assessed for composite endpoints reflecting heart failure (HF), life-threatening ventricular arrhythmias, atrial fibrillation (AF), and an overall composite that also included stroke and death. Stratifying by age of diagnosis, 184 (2.4%) patients were diagnosed in infancy; 1128 (14.7%) in childhood; and 6365 (82.9%) in adulthood. Childhood-onset HCM patients had an ∼2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the 1st decade following baseline visit, but HF and AF becoming more common by the end of the 2nd decade. Sarcomeric variants were more common in childhood-onset HCM (63%) and carried a worse prognosis than non-sarcomeric disease, including a greater than two-fold increased risk of HF [HRadj 2.39 (1.36–4.20), P = 0.003] and 67% increased risk of the overall composite outcome [HRadj 1.67 (1.16–2.41), P = 0.006]. When compared with adult-onset HCM, childhood-onset was 36% more likely to develop life-threatening ventricular arrhythmias [HRadj 1.36 (1.03–1.80)] and twice as likely to require transplant or ventricular assist device [HRadj 1.99 (1.23–3.23)]. Conclusion Patients with childhood-onset HCM are more likely to have sarcomeric disease, carry a higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. These findings provide insight into the natural history of disease and can help inform clinical risk stratification.

Further Considerations in Childhood-Onset Hypertrophic Cardiomyopathy Genetic Testing

“…We read with great interest a recently published report by Marston et al ( 12 ) investigating the natural history of childhood-onset HCM, the impact of the genetic background, and comparing outcomes to adult-onset disease. HCM may present clinically during all phases of life, yet a higher risk of developing life-threatening ventricular arrhythmias or requiring a transplant or vascular assist device have been associated with earlier disease onset.…”

“…Marston et al ( 12 ) performed genetic testing focusing on eight sarcomeric genes. Additionally, the genetic analysis of the genotyped cohort carried out by Marston et al ( 12 ) still refers to HCM as a monogenic disease.…”

“…Marston et al ( 12 ) performed genetic testing focusing on eight sarcomeric genes. Additionally, the genetic analysis of the genotyped cohort carried out by Marston et al ( 12 ) still refers to HCM as a monogenic disease. Today, the traditional Mendelian fashion of inheritance has been replaced by the oligogenic inheritance model ( 13 , 14 ), meaning that a mutational load can cause the HCM phenotype.…”

“…Moreover, in a nationwide study of Finnish patients ( 16 ), 49 variants of unknown significance (VUS) in 31 genes were detected in 20.4% of cases. Marston et al ( 12 ) excluded patients with VUS. It would have been useful to know what VUS had been identified and which criteria had been employed to categorize them as such.…”

“…Regarding again the study by Marston et al ( 12 ), it was unclear how “clinical significance” was defined when describing patients with “no clinically significant sarcomeric variants” who were classified as non-sarcomeric HCM. Furthermore, it would have been interesting to know what variants in non-sarcomeric proteins were excluded entirely from the study.…”