Pulmonary hypertension in heart failure with preserved ejection fraction

In heart failure with preserved ejection fraction (HFpEF), an entity that remains challenging and difficult to treat, the development of pulmonary hypertension (PH), via an increase in left atrial pressure, is the direct consequence of reduced relaxation and enhanced stiffness of the left ventricle and is now viewed as an important contributor to clinical worsening and increased mortality. PH becomes a relevant clinical phenotype in approximately 50% of patients with HFpEF and represents a true challenge in the clinical follow-up and management of these patients. Along with these epidemiologic insights, there has been increasing recognition of the pathophysiology of PH and its consequences on the right ventricle in patients with HFpEF. Novel and effective therapeutic interventions aimed at preventing and reversing PH are highly relevant in the attempt to modify the poor clinical trajectory and growing health care burden of HFpEF. Many theoretical rationales as well as progressively accumulating evidence support the usefulness of nitric oxide pathway-potentiating compounds in targeting the lung vasculature through phosphodiesterase 5 inhibitors or guanylate cyclase stimulators to produce vasodilation and potentially a biologic effect. These pharmacologic strategies may be clinically effective options for the treatment of PH in patients with HFpEF; however, large controlled trials are necessary to address definitively the safety, tolerability, and potential impact on morbidity and mortality. This review details the pathophysiologic process, prevalence, and consequences of HFpEF-associated PH and discusses current and emerging treatment strategies to prevent or treat this deleterious sequela when present.