title: Quantification and significance of diffuse myocardial fibrosis and diastolic dysfunction in childhood hypertrophic cardiomyopathy.
abstract: The purpose of this study was to evaluate the presence of diffuse myocardial fibrosis in children and adolescents with hypertrophic cardiomyopathy (HCM) and to assess associations with echocardiographic and clinical parameters of disease. While a common end point in adults with HCM, it is unclear whether diffuse myocardial fibrosis occurs early in the disease. Cardiac magnetic resonance (CMR) estimation of myocardial post-contrast longitudinal relaxation time (T1) is an increasingly used method to estimate diffuse fibrosis. T1 measurements were taken using standard multi-breath-hold spoiled gradient echo phase-sensitive inversion-recovery CMR before and 15 min after the injection of gadolinium. The tissue-blood partition coefficient was calculated as a function of the ratio of T1 change of myocardium compared with blood. An echocardiogram and blood brain natriuretic peptide (BNP) levels were obtained on the day of the CMR. Twelve controls (mean age 12.8 years; 7 male) and 28 patients with HCM (mean age 12.8 years; 21 male) participated. The partition coefficient for both septal (0.27 ± 0.17 vs. 0.13 ± 0.09; p = 0.03) and lateral walls (0.22 ± 0.09 vs. 0.07 ± 0.10; p < 0.001) was increased in patients compared with controls. Eight patients had overt areas of late gadolinium enhancement (LGE). These patients did not show increased partition coefficient compared with those without LGE (0.27 ± 0.15 vs. 0.27 ± 0.19 and 0.22 ± 0.09 vs. 0.22 ± 0.09; p = 0.95 and 0.98, respectively). However, patients who were symptomatic (dyspnea, arrhythmia and/or chest pain) had higher lateral wall partition coefficient than asymptomatic HCM patients (0.27 ± 0.08 vs. 0.17 ± 0.08; p = 0.006). Similarly, patients with raised BNP (>100 pg/ml) had raised lateral wall coefficients (0.27 ± 0.07 vs. 0.20 ± 0.07; p = 0.03), as did those with traditional risk factors for sudden death (0.27 ± 0.06 vs. 0.18 ± 0.08; p = 0.007). Diffuse fibrosis, measured by the partition coefficient technique, is demonstrable in children and adolescents with HCM. Markers of fibrosis show an association with symptoms and raised serum BNP. Further study of the prognostic implication of this technique in young patients with HCM is warranted.
authors.affiliation: Department of Pediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada, tarique@doctors.org.uk.
authors.forename: Tarique
authors.initials: T
authors.lastname: Hussain
authors.forename: Andreea
authors.initials: A
authors.lastname: Dragulescu
authors.forename: Lee
authors.initials: L
authors.lastname: Benson
authors.forename: Shi-Joon
authors.initials: SJ
authors.lastname: Yoo
authors.forename: Howard
authors.initials: H
authors.lastname: Meng
authors.forename: Jonathan
authors.initials: J
authors.lastname: Windram
authors.forename: Derek
authors.initials: D
authors.lastname: Wong
authors.forename: Andreas
authors.initials: A
authors.lastname: Greiser
authors.forename: Mark
authors.initials: M
authors.lastname: Friedberg
authors.forename: Luc
authors.initials: L
authors.lastname: Mertens
authors.forename: Michael
authors.initials: M
authors.lastname: Seed
authors.forename: Andrew
authors.initials: A
authors.lastname: Redington
authors.forename: Lars
authors.initials: L
authors.lastname: Grosse-Wortmann
mesh_terms: D000293:Adolescent; D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging / Q000473:pathology*; D002648:Child; D003287:Contrast Media; D003971:Diastole; D004452:Echocardiography; D005260:Female; D005355:Fibrosis; D019786:Gadolinium DTPA; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009206:Myocardium / Q000473:pathology*; D018754:Ventricular Dysfunction / Q000000981:diagnostic imaging / Q000473:pathology*
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA