TTN and hypertrophic cardiomyopathy: Titin stiffness also enhances myofilament Ca2+ sensitivity and systolic force production.11,63,64 Consequently, reducing titin stiffness using Rbm20-ASO could benefit certain cases of hypertrophic cardiomyopathy (HCM) associated with diastolic dysfunction, hypercontractility, and LV outflow tract obstruction.65 Moreover, by reducing mutant RBM20 production, ASOs may mitigate the severity of Rbm20 cardiomyopathy by decreasing cytoplasmic RBM20 granule accumulation, although further investigation is required.