TTN and heart failure: This is significant, because relative to both aortic stenosis and heart failure with reduced ejection fraction (HFrEF) [5], HFpEF patients show reduced myocardial PKG activity and lower cGMP concentrations, both of which are associated with increased titin-based stiffness, titin hypophosphorylation and elevated myocardial nitrotyrosine levels, indicative of raised nitrosative/oxidative stress [5].