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Echocardiographic evaluation of pre-diagnostic development in young relatives genetically predisposed to hypertrophic cardiomyopathy

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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.

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Acknowledgments

This study was supported by the Lundbeck foundation (Grant No. R7-A675-B311), Dagmar Marshalls Fond and The A.P. Møller Foundation for the Advancement of Medical Science.

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Authors have no conflicts of interests.

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Authors and Affiliations

  1. The Unit for Inherited Heart Diseases, The Heart Center, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Morten K. Jensen, Anna Axelsson, Lars Køber & Henning Bundgaard

  2. Department of Cardiology, Roskilde Sygehus, Roskilde, Denmark

    Ole Havndrup

  3. Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark

    Michael Christiansen & Paal S. Andersen

Authors
  1. Morten K. Jensen
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  2. Ole Havndrup
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  3. Michael Christiansen
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  4. Paal S. Andersen
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  5. Anna Axelsson
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  6. Lars Køber
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  7. Henning Bundgaard
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Correspondence to Morten K. Jensen.

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Jensen, M.K., Havndrup, O., Christiansen, M. et al. Echocardiographic evaluation of pre-diagnostic development in young relatives genetically predisposed to hypertrophic cardiomyopathy. Int J Cardiovasc Imaging 31, 1511–1518 (2015). https://doi.org/10.1007/s10554-015-0723-x

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  • DOI: https://doi.org/10.1007/s10554-015-0723-x

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