Abstract
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.
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Details
1 Utrecht University, Department of Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands (GRID:grid.5477.1) (ISNI:0000000120346234)
2 University of Groningen, Department of Genetics, University Medical Centre Groningen, Groningen, The Netherlands (GRID:grid.4830.f) (ISNI:0000 0004 0407 1981)
3 University of Amsterdam, Department of Clinical Genetics, Amsterdam UMC, Amsterdam, The Netherlands (GRID:grid.7177.6) (ISNI:0000000084992262)
4 Erasmus University Medical Centre, Department of Cardiology, Thoraxcenter, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X)
5 University of Groningen, Department of Genetics, University Medical Centre Groningen, Groningen, The Netherlands (GRID:grid.4830.f) (ISNI:0000 0004 0407 1981); Radboud University Medical Centre, Department of Clinical Genetics, Nijmegen, The Netherlands (GRID:grid.10417.33) (ISNI:0000 0004 0444 9382)
6 University of Amsterdam, Heart Centre, Clinical and Experimental Cardiology, Amsterdam UMC, Amsterdam, The Netherlands (GRID:grid.7177.6) (ISNI:0000000084992262)
7 Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Department of Physiology, Amsterdam UMC, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227)
8 University of Groningen, Department of Cardiology, University Medical Centre Groningen, Groningen, The Netherlands (GRID:grid.4830.f) (ISNI:0000 0004 0407 1981)
9 Utrecht University, Department of Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands (GRID:grid.5477.1) (ISNI:0000000120346234); Netherlands Heart Institute, Utrecht, The Netherlands (GRID:grid.411737.7)
10 Netherlands Heart Institute, Utrecht, The Netherlands (GRID:grid.411737.7); University Medical Centre Utrecht, Department of Cardiology, Utrecht, The Netherlands (GRID:grid.7692.a) (ISNI:0000000090126352); University College London, Institute of Cardiovascular Science, Faculty of Population Health Sciences, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); University College London, Health Data Research UK and Institute of Health Informatics, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201)