TY - JOUR
T1 - BIO FOr CARE
T2 - biomarkers of hypertrophic cardiomyopathy development and progression in carriers of Dutch founder truncating MYBPC3 variants—design and status
AU - Jansen, M.
AU - Christiaans, I.
AU - van der Crabben, S. N.
AU - Michels, M.
AU - Huurman, R.
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 - Jans, J. J.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: an initiative with the support of the Dutch Heart Foundation (CVON2014-40 DOSIS to F.W.A., J.P.v.T., J.v.d.V, M.M. and R.A.d.B.; CVON2015-12 e‑Detect to F.W.A, J.P.v.T.; CVON2018-30 PREDICT2 to A.A.M.W., J.P.v.T. and R.A.d.B); the Dutch Heart Foundation (Dekker 2015T041 to A.F.B. and M.J.); the Netherlands Organization for Sciences (NWO)-ZonMW (VICI 91818602 to J.v.d.V.); ZonMW and the Dutch Heart Foundation for the translational research program ENERY trial, project 95105003 (to J.v.d.V and M.M.); UCL Hospitals NIHR Biomedical Research Centre (to F.W.A.).
Publisher Copyright: © 2021, The Author(s).
PY - 2021/2/2
Y1 - 2021/2/2
N2 - Background: Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease, commonly caused by truncating variants in the MYBPC3 gene. HCM is an important cause of sudden cardiac death; however, overall prognosis is good and penetrance in genotype-positive individuals is incomplete. The underlying mechanisms are poorly understood and risk stratification remains limited. Aim: To create a nationwide cohort of carriers of truncating MYBPC3 variants for identification of predictive biomarkers for HCM development and progression. Methods: In the multicentre, observational BIO FOr CARe (Identification of BIOmarkers of hypertrophic cardiomyopathy development and progression in Dutch MYBPC3 FOunder variant CARriers) cohort, carriers of the c.2373dupG, c.2827C > T, c.2864_2865delCT and c.3776delA MYBPC3 variants are included and prospectively undergo longitudinal blood collection. Clinical data are collected from first presentation onwards. The primary outcome constitutes a composite endpoint of HCM progression (maximum wall thickness ≥ 20 mm, septal reduction therapy, heart failure occurrence, sustained ventricular arrhythmia and sudden cardiac death). Results: So far, 250 subjects (median age 54.9 years (interquartile range 43.3, 66.6), 54.8% male) have been included. HCM was diagnosed in 169 subjects and dilated cardiomyopathy in 4. The primary outcome was met in 115 subjects. Blood samples were collected from 131 subjects. Conclusion: BIO FOr CARe is a genetically homogeneous, phenotypically heterogeneous cohort incorporating a clinical data registry and longitudinal blood collection. This provides a unique opportunity to study biomarkers for HCM development and prognosis. The established infrastructure can be extended to study other genetic variants. Other centres are invited to join our consortium.
AB - Background: Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease, commonly caused by truncating variants in the MYBPC3 gene. HCM is an important cause of sudden cardiac death; however, overall prognosis is good and penetrance in genotype-positive individuals is incomplete. The underlying mechanisms are poorly understood and risk stratification remains limited. Aim: To create a nationwide cohort of carriers of truncating MYBPC3 variants for identification of predictive biomarkers for HCM development and progression. Methods: In the multicentre, observational BIO FOr CARe (Identification of BIOmarkers of hypertrophic cardiomyopathy development and progression in Dutch MYBPC3 FOunder variant CARriers) cohort, carriers of the c.2373dupG, c.2827C > T, c.2864_2865delCT and c.3776delA MYBPC3 variants are included and prospectively undergo longitudinal blood collection. Clinical data are collected from first presentation onwards. The primary outcome constitutes a composite endpoint of HCM progression (maximum wall thickness ≥ 20 mm, septal reduction therapy, heart failure occurrence, sustained ventricular arrhythmia and sudden cardiac death). Results: So far, 250 subjects (median age 54.9 years (interquartile range 43.3, 66.6), 54.8% male) have been included. HCM was diagnosed in 169 subjects and dilated cardiomyopathy in 4. The primary outcome was met in 115 subjects. Blood samples were collected from 131 subjects. Conclusion: BIO FOr CARe is a genetically homogeneous, phenotypically heterogeneous cohort incorporating a clinical data registry and longitudinal blood collection. This provides a unique opportunity to study biomarkers for HCM development and prognosis. The established infrastructure can be extended to study other genetic variants. Other centres are invited to join our consortium.
UR - http://www.scopus.com/inward/record.url?scp=85100310564&partnerID=8YFLogxK
U2 - 10.1007/s12471-021-01539-w
DO - 10.1007/s12471-021-01539-w
M3 - Article
AN - SCOPUS:85100310564
VL - 29
SP - 318
EP - 329
JO - Netherlands Heart Journal
JF - Netherlands Heart Journal
SN - 1568-5888
IS - 6
ER -