Insights into the pulmonary vascular complications of heart failure with preserved ejection fraction

Abstract

Pulmonary hypertension in the setting of heart failure with preserved ejection fraction (PH-HFpEF) is a growing public health problem that is increasing in prevalence. While PH-HFpEF is defined by a high mean pulmonary artery pressure, high left ventricular end-diastolic pressure and a normal ejection fraction, some HFpEF patients develop PH in the presence of pulmonary vascular remodelling with a high transpulmonary pressure gradient or pulmonary vascular resistance. Ageing, increased left atrial pressure and stiffness, mitral regurgitation, as well as features of metabolic syndrome, which include obesity, diabetes and hypertension, are recognized as risk factors for PH-HFpEF. Qualitative studies have documented that patients with PH-HFpEF develop more severe symptoms than those with HFpEF and are associated with more significant exercise intolerance, frequent hospitalizations, right heart failure and reduced survival. Currently, there are no effective therapies for PH-HFpEF, although a number of candidate drugs are being evaluated, including soluble guanylate cyclase stimulators, phosphodiesterase type 5 inhibitors, sodium nitrite and endothelin receptor antagonists. In this review we attempt to provide an updated overview of recent findings pertaining to the pulmonary vascular complications in HFpEF in terms of clinical definitions, epidemiology and pathophysiology. Mechanisms leading to pulmonary vascular remodelling in HFpEF, a summary of pre-clinical models of HFpEF and PH-HFpEF, and new candidate therapeutic strategies for the treatment of PH-HFpEF are summarized.

Keywords: PH-HFpEF; heart failure with preserved ejection fraction; pulmonary hypertension.

Figure 1. Classification of subtypes and diagnostic factors of PH‐HFpEF

CpcPH, combined post‐capillary and pre‐capillary pulmonary hypertension; DPG, diastolic pressure gradient (defined as diastolic pulmonary artery pressure – PAWP); IpcPH, isolated post‐capillary pulmonary hypertension; LA, left atrium; LV, left ventricle; LVEF, left ventricular ejection fraction; mPAP, mean pulmonary artery pressure; PAWP, pulmonary arterial wedge pressure; PVR, pulmonary vascular resistance; RA, right atrium; RV, right ventricle.

Figure 2. Pulmonary vascular complications in HFpEF

ENaC, epithelial sodium channel; LA, left atrium; LV, left ventricle; PA, pulmonary artery; PV, pulmonary vein; PVR, pulmonary vascular resistance; RV, right ventricle.