Advances in Clinical Trials

Treatment for Heart Failure With Preserved Ejection Fraction Is an Unmet Public Health Need Heart failure (HF) with preserved ejection fraction (HFpEF) currently represents about half of all patients with HF. As the world’s population ages and comorbidities associated with HFpEF become increasingly common, the prevalence is expected to continue to grow. Clinical trials performed to date have failed to identify an effective pharmacological treatment for HFpEF. Exercise intolerance, manifest by dyspnea, fatigue, and depressed aerobic capacity, is the cardinal symptomatic manifestation of HFpEF. Novel treatments that can improve exercise capacity in HFpEF are, therefore, urgently needed. Pathophysiology of HFpEF The pathophysiology of HFpEF is complex; abnormalities in left ventricular (LV) diastolic and systolic function, chronotropic incompetence, arterial stiffening, endothelial dysfunction, depressed vasodilator reserve, impaired right ventricular (RV) pulmonary artery (PA) coupling, atrial dysfunction, and abnormalities in skeletal muscle have all been related to the HFpEF syndrome (Figure 1). The extent to which these abnormalities exist in a given patient may vary, which complicates targeting of treatment. Exercise capacity is constrained in some patients with HFpEF predominantly by central (cardiac) limitations, whereas in others the major limitation seems to reside in skeletal muscle and systemic vasculature (Figure 1). Advances in Clinical Trials