M Jansen1, I Christiaans2, S N van der Crabben3, M Michels4, R Huurman4, Y M Hoedemaekers2,5, D Dooijes6, J D H Jongbloed2, L G Boven2, R H Lekanne Deprez3, A A M Wilde7, J J M Jans6, J van der Velden8, R A de Boer9, J P van Tintelen6,10, F W Asselbergs10,11,12,13, A F Baas6. 1. Department of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands. m.jansen-2@umcutrecht.nl. 2. Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. 3. Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 4. Department of Cardiology, Thoraxcenter, Erasmus University Medical Centre, Rotterdam, The Netherlands. 5. Department of Clinical Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands. 6. Department of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands. 7. Heart Centre, Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 8. Department of Physiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands. 9. Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. 10. Netherlands Heart Institute, Utrecht, The Netherlands. 11. Department of Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands. 12. Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK. 13. Health Data Research UK and Institute of Health Informatics, University College London, London, UK.
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.
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.3776delAMYBPC3 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.
Authors: Hannah G van Velzen; Arend F L Schinkel; Sara J Baart; Rogier A Oldenburg; Ingrid M E Frohn-Mulder; Marjon A van Slegtenhorst; Michelle Michels Journal: Circ Genom Precis Med Date: 2018-04
Authors: Hannah G van Velzen; Arend F L Schinkel; Rogier A Oldenburg; Marjon A van Slegtenhorst; Ingrid M E Frohn-Mulder; Jolanda van der Velden; Michelle Michels Journal: Circ Cardiovasc Genet Date: 2017-08