TY - JOUR
T1 - Circulating Acylcarnitines Associated with Hypertrophic Cardiomyopathy Severity
T2 - an Exploratory Cross-Sectional Study in MYBPC3 Founder Variant Carriers
AU - Jansen, Mark
AU - Schmidt, A. F.
AU - Jans, J. J. M.
AU - Christiaans, I.
AU - van der Crabben, S. N.
AU - Hoedemaekers, Y. M.
AU - Dooijes, D.
AU - Jongbloed, J. D. H.
AU - Boven, L. G.
AU - Lekanne Deprez, R. H.
AU - Wilde, A. A. M.
AU - van der Velden, J.
AU - de Boer, R. A.
AU - van Tintelen, J. P.
AU - Asselbergs, F. W.
AU - Baas, A. F.
N1 - Funding Information: This work was supported by the Netherlands Cardiovascular Research Initiative with the support of the Dutch Heart Foundation (CVON2014-40 DOSIS, Dutch Cardiovascular Alliance 2020B005 DoubleDose to M.J., A.F.B, F.W.A., J.P.v.T., R.A.d.B. and J.v.d.V.; CVON2015-12 e-Detect to F.W.A, J.P.v.T. and I.C.), the Dutch Heart Foundation (Dekker 2015T041 to A.F.B. and M.J.), University College London Hospitals National Institute for Health and Care Research Biomedical Research Centre (to F.W.A.), and British Heart Foundation (PG/18/5033837, PG/22/10989 and University College London/British Heart Foundation Research Accelerator AA/18/6/34223 to A.F.S.). Publisher Copyright: © 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease characterised by myocardial hypertrophy. HCM can cause outflow tract obstruction, sudden cardiac death and heart failure, but severity is highly variable. In this exploratory cross-sectional study, circulating acylcarnitines were assessed as potential biomarkers in 124 MYBPC3 founder variant carriers (59 with severe HCM, 26 with mild HCM and 39 phenotype-negative [G + P-]). Elastic net logistic regression identified eight acylcarnitines associated with HCM severity. C3, C4, C6-DC, C8:1, C16, C18 and C18:2 were significantly increased in severe HCM compared to G + P-, and C3, C6-DC, C8:1 and C18 in mild HCM compared to G + P-. In multivariable linear regression, C6-DC and C8:1 correlated to log-transformed maximum wall thickness (coefficient 5.01, p = 0.005 and coefficient 0.803, p = 0.007, respectively), and C6-DC to log-transformed ejection fraction (coefficient -2.50, p = 0.004). Acylcarnitines seem promising biomarkers for HCM severity, however prospective studies are required to determine their prognostic value. Graphical abstract: [Figure not available: see fulltext.].
AB - Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease characterised by myocardial hypertrophy. HCM can cause outflow tract obstruction, sudden cardiac death and heart failure, but severity is highly variable. In this exploratory cross-sectional study, circulating acylcarnitines were assessed as potential biomarkers in 124 MYBPC3 founder variant carriers (59 with severe HCM, 26 with mild HCM and 39 phenotype-negative [G + P-]). Elastic net logistic regression identified eight acylcarnitines associated with HCM severity. C3, C4, C6-DC, C8:1, C16, C18 and C18:2 were significantly increased in severe HCM compared to G + P-, and C3, C6-DC, C8:1 and C18 in mild HCM compared to G + P-. In multivariable linear regression, C6-DC and C8:1 correlated to log-transformed maximum wall thickness (coefficient 5.01, p = 0.005 and coefficient 0.803, p = 0.007, respectively), and C6-DC to log-transformed ejection fraction (coefficient -2.50, p = 0.004). Acylcarnitines seem promising biomarkers for HCM severity, however prospective studies are required to determine their prognostic value. Graphical abstract: [Figure not available: see fulltext.].
KW - Acylcarnitine
KW - Biomarker
KW - Hypertrophic Cardiomyopathy
KW - MYBPC3
KW - Metabolism
UR - http://www.scopus.com/inward/record.url?scp=85161306588&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s12265-023-10398-2
DO - https://doi.org/10.1007/s12265-023-10398-2
M3 - Article
C2 - 37278928
SN - 1937-5387
VL - 16
SP - 1267
EP - 1275
JO - Journal of cardiovascular translational research
JF - Journal of cardiovascular translational research
IS - 6
ER -