TTN and heart failure: Following short-term cGMP-enhancing treatment with sildenafil and B-type natriuretic peptide (BNP) in an animal model of heart failure with preserved ejection fraction (HFpEF) (elderly hypertensive dogs) (Bishu et al., 2011), PKG-mediated phosphorylation of titin resulted in acutely increased cardiac extensibility and may also positively regulate hypertrophic signaling.