Progression of LGE in Children With Hypertrophic Cardiomyopathy

Study Questions:

What is the prevalence of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) in young adults and adolescents with hypertrophic cardiomyopathy (HCM), how does it evolve over time, and how is it related to clinical outcomes?

Methods:

The authors conducted a retrospective analysis combining 39 subjects from the HCMNet study and an additional 156 subjects from nine participating institutions. Patients were classified as overt HCM or mutation carriers without left ventricular hypertrophy (LVH) on the basis of LV wall thickness ≥15 mm or z-score >3 (with sarcomere mutation or family history of HCM) or z-score >5 (without sarcomere mutation or family history of HCM). CMR was performed on 1.5 or 3 Tesla scanners with measurements of LV volumes and function from gated imaging and replacement fibrosis using post-contrast LGE imaging.

Results:

Of 195 total subjects, 155 (79%) had overt HCM. Mean age was 11.4 ± 5.4 years with a mean time between diagnosis and CMR of 3.3 ± 3.9 years. Mean maximal LV wall thickness was 22.4 ± 8.4 mm and the median z-score was 15.7. LV ejection fraction (LVEF) was normal in all but three patients. LGE was detected in 70/152 (46%) patients with overt HCM who underwent contrast-enhanced imaging, but in none of the subjects who were genotype positive without LVH. Only one of three patients in reduced LVEF had LGE. LGE most commonly occurred in the segments with most hypertrophy (83% of patients with LGE). The median extent of LGE was 3.3%-8.5% depending on the quantification technique used. Among the 31 patients with repeating CMR, 42% had LGE at baseline, which increased to 52% on follow-up. On average, the extent of LGE increased from 1.5 to 7.5 g (p = 0.01). No predictors of change in LGE were identified. Twenty-eight (18%) subjects experienced an adverse event such as death, aborted sudden cardiac death, appropriate implantable cardioverter-defibrillator therapy, heart transplantation, or atrial fibrillation. Of the four patients who died, only one had LGE on CMR. No significant differences in rates of adverse events were seen among those with or without LGE.

Conclusions:

Replacement fibrosis, as measured by LGE on CMR, is commonly found in children and adolescents with HCM, and is generally progressive, but may not be associated with adverse prognosis.

Perspective:

This is the largest study to date to evaluate the prevalence and significance of LGE in children and adolescents. Prior studies in adults have generally shown LGE to be a powerful marker of adverse prognosis. In this study, although LGE was common, it was not clearly associated with LV systolic dysfunction or adverse clinical outcomes. This suggests that: 1) there are protective mechanisms in children, which are lost with aging; 2) there are other critical factors necessary for LGE to increase risk of adverse outcomes; or 3) other factors such as outflow obstruction outweigh the impact of LGE in children. Importantly, this is still a relatively small study for prognostic evaluation, and effect sizes might be better evaluated with larger future studies.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and CHD and Pediatrics, Cardiac Surgery and Heart Failure, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Imaging, CHD and Pediatrics and Interventions, Acute Heart Failure, Heart Transplant, Interventions and Imaging, Interventions and Structural Heart Disease, Magnetic Resonance Imaging

Keywords: Adolescent, Atrial Fibrillation, Cardiomyopathy, Hypertrophic, Child, Death, Sudden, Cardiac, Defibrillators, Implantable, Diagnostic Imaging, Fibrosis, Gadolinium, Genotype, Heart Failure, Heart Transplantation, Hypertrophy, Left Ventricular, Magnetic Resonance Imaging, Mutation, Pediatrics, Prevalence, Sarcomeres, Stroke Volume


< Back to Listings