Hypertrophic cardiomyopathy - Integration of genotype and deep phenotype to tailor therapy
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. In 30–40% of cases, a mutation in sarcomere protein genes is identified, while 10% have a non-sarcomere mutation; the remaining cases remain genetically undiagnosed.
Most patients with obstructive HCM (oHCM) present with some degree of exercise-induced symptoms and a reduced VO₂peak, a strong prognostic marker for adverse outcomes.
Recently, two novel therapeutic options have emerged in the treatment landscape of oHCM:
1. Cardiac myosin inhibitors (mavacamten): This new class of disease-specific drugs reduces cardiac hypercontractility and increases VO₂peak. It may provide greater benefits in patients with sarcomere gene mutations, but in vitro cell models and larger patient cohorts are needed to determine whether sarcomere variant status influences treatment response.
2. Exercise training: There is growing evidence that structured exercise is a safe and effective strategy to improve VO₂peak. However, whether exercise training provides additional benefits in oHCM patients treated with mavacamten and which mechanisms underlie these training-induced improvements remain to be elucidated.
We aim to gain a fundamental understanding of how phenotype and genotype influence treatment response in HCM, using both clinical studies and iPSC-derived cardiomyocytes and engineered heart tissue models carrying sarcomere and non-sarcomere mutations. Our ultimate goal is to advance precision therapy for HCM.
Researcher: Seghers Hanna
Promotor: Van Craenenbroeck Emeline
Co-promotor: Maaike Alaerts