Combined post- and pre-capillary pulmonary hypertension in heart failure with preserved ejection fraction

Over 2.5 million patients in the USA suffer from heart failure with preserved ejection fraction (HFpEF), and pulmonary hypertension (PH) is present in the majority of these patients. PH represents an adverse prognostic factor in HFpEF and has been identified as a potential therapeutic target to improve symptoms and outcomes. The recognition and investigation of a subset of patients with superimposed pulmonary vascular disease (on top of pulmonary venous hypertension) has led to further subclassification of PH due to left heart disease (PH-LHD) into two categories: isolated post-capillary PH and combined post- and pre-capillary PH (CpcPH). In this review, we (1) describe the evolution of the diagnostic criteria of PH-LHD; (2) identify the diagnostic modalities that can be utilized for the identification of patients with CpcPH-HFpEF; (3) review the literature on the prevalence, clinical characteristics, and prognostic factors of CpcPH-HFpEF; (4) discuss recent and ongoing clinical trials investigating the effectiveness of selective pulmonary vasodilators in PH-LHD; and (5) propose future areas for further investigation of the etiology and pathophysiological mechanisms contributing to the development of CpcPH and highlight important considerations in the design of future trials to promote better characterization of this clinical entity. CpcPH-HFpEF is a distinct subset within HFpEF and one that may respond to targeted therapeutics.