TTN and familial dilated cardiomyopathy: Modulation of titin compliance is linked to human cardiac disease (2), with decreased titin-based passive stiffness observed in patients with systolic dysfunction and dilated cardiomyopathy (DCM) (3–6), and titin stiffening associated with diastolic dysfunction (DD) and heart failure with preserved ejection fraction (HFpEF) (7–10).