title: Echocardiographic evaluation of pre-diagnostic development in young relatives genetically predisposed to hypertrophic cardiomyopathy.
abstract: Identification of the first echocardiographic manifestations of hypertrophic cardiomyopathy may be important for clinical management and our understanding of the pathogenesis. We studied the development of pre-diagnostic echocardiographic changes in young relatives to HCM patients during long-term years follow-up. HCM-relatives not fulfilling the diagnostic criteria for HCM and age of <18 years were included in this study. We performed echocardiographic evaluations at inclusion and after 12 ± 1 years follow-up. Based on family screening of 11 sarcomere genes, CRYAB, α-GAL, and titin, we evaluated: (1) non-carriers (known family mutation ruled out-controls), (2) carriers (phenotype negative gene mutation carriers) and (3) phenotype negative relatives with unknown genetic status (relatives from families without identified mutations). At inclusion (age 11 ± 5 years), there were no differences in echocardiographic chamber dimensions, systolic or diastolic function between the three groups. During follow-up (age 23 ± 5 years), carriers (n = 8) developed lower left ventricular end-diastolic dimension (LVEDd) compared to non-carriers (n = 23) (41 ± 4 vs. 46 ± 4 mm; p = 0.04) and a higher ratio of early left ventricular filling velocity and early diastolic velocity of lateral mitral annulus (E/e' 6 ± 1 vs. 5 ± 1; p = 0.003). No significant differences in LVEDd or E/e' were found between relatives with unknown genetic status (n = 24) and non-carriers though Z-scores for these parameters were >2 in a subset of relatives with unknown genetic status. Children carrying pathogenic sarcomere gene mutations develop reduced LVEDd and increased E/e' as first pre-diagnostic echocardiographic manifestations during follow-up into adulthood.
authors.affiliation: The Unit for Inherited Heart Diseases, The Heart Center, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. mortenjensen@dadlnet.dk.
authors.forename: Morten K
authors.initials: MK
authors.lastname: Jensen
authors.affiliation: Department of Cardiology, Roskilde Sygehus, Roskilde, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Havndrup
authors.affiliation: Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
authors.affiliation: Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Paal S
authors.initials: PS
authors.lastname: Andersen
authors.affiliation: The Unit for Inherited Heart Diseases, The Heart Center, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Anna
authors.initials: A
authors.lastname: Axelsson
authors.affiliation: The Unit for Inherited Heart Diseases, The Heart Center, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.affiliation: The Unit for Inherited Heart Diseases, The Heart Center, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Bundgaard
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D058070:Asymptomatic Diseases; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D004252:DNA Mutational Analysis; D018450:Disease Progression; D015150:Echocardiography, Doppler; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D008297:Male; D008943:Mitral Valve / Q000000981:diagnostic imaging / Q000503:physiopathology; D009154:Mutation; D015588:Observer Variation; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D012307:Risk Factors; D013318:Stroke Volume; D013997:Time Factors; D016277:Ventricular Function, Left; D055815:Young Adult
chemical_list: D005819:Genetic Markers
keywords: Cardiomyopathy; Carriers; Children; Diastolic function; Dimensions; Family screening; Hypertrophy; Inherited heart disease; Left ventricle; Sarcomere gene mutation