Structured Graphical Abstract.

As compared to control subjects without heart failure (black), patients with HFpEF and low NTproBNP levels (<125 ng/L, green) displayed increased risk for the combined endpoint of heart failure hospitalization or death, with greater reliance on an increase in left ventricular transmural pressure (LVTMP) to increase cardiac output during exercise. As compared to patients with HFpEF and lower NTproBNP, those with elevated NTproBNP (red) displayed the greatest risk for heart failure hospitalization or death, with more severely impaired cardiac output reserve, greater right ventricular (RV) remodeling, and higher prevalence of secondary (functional) mitral and tricuspid insufficiency.