Association Between Hemodynamic Markers of Pulmonary Hypertension and Outcomes in Heart Failure With Preserved Ejection Fraction

Abstract

Importance: Heart failure with preserved ejection fraction (HFpEF) is highly prevalent, yet there are no specific therapies, possibly due to phenotypic heterogeneity. The development of pulmonary hypertension (PH) in patients with HFpEF is considered a high-risk phenotype in need of targeted therapies, but there have been limited hemodynamic and outcomes data.

Objective: To identify the hemodynamic characteristics and outcomes of PH-HFpEF.

Design, setting, and participants: Cohort study of participants who had a right heart catheterization from January 2005 to September 2012 (median [interquartile range] follow-up time, 1578 [554-2513] days) were analyzed. Hemodynamic catheterization data was linked to the clinical data repository of all inpatient and outpatient encounters across a health system. Single tertiary referral center for heart failure and PH within a large health care network using a common clinical data repository was studied. There were 19 262 procedures in 10 023 participants.

Exposures: Participants were classified as having no PH, precapillary PH, or PH in the setting of left heart disease (reduced or preserved ejection fraction). Pulmonary hypertension associated with HFpEF was defined as mean pulmonary artery pressure of 25 mm Hg or more, pulmonary artery wedge pressure of 15 mm Hg or more, and left ventricular ejection fraction of 45% or more. Pulmonary hypertension severity was quantified by the hemodynamic parameters transpulmonary gradient, pulmonary vascular resistance, and diastolic pulmonary gradient.

Main outcomes and measures: The primary outcome was time to all-cause mortality. Secondary outcomes were time to acute hospitalization and cardiovascular hospitalization.

Results: The mean (SD) of all study individuals was 65 (38) years. Of 10 023 individuals, 2587 (25.8%) had PH-HFpEF. Mortality was 23.6% at 1 year and 48.2% at 5 years. Cardiac hospitalizations occurred in 28.1% at 1 year and 47.4% at 5 years. The frequency of precapillary PH using clinically defined cut-offs for transpulmonary gradient (>12 mm Hg), pulmonary vascular resistance (3 Woods units), and diastolic pulmonary gradient (≥7 mm Hg) were 12.6%, 8.8%, and 3.5%, respectively. Transpulmonary gradient, pulmonary vascular resistance, and diastolic pressure gradient were predictive of mortality and cardiac hospitalizations.

Conclusions and relevance: In a large cohort referred for invasive hemodynamic assessment, PH-HFpEF was common. Transpulmonary gradient, pulmonary vascular resistance, and diastolic pulmonary gradient are all associated with mortality and cardiac hospitalizations.

Figure 1.. Flow Diagram of the Cohort

Participants with a documented ejection fraction of 45% or more were classified as having a preserved ejection fraction or pulmonary hypertension in the setting of heart failure preserved ejection fraction (PH-HFpEF). Participants with an left ventricular ejection fraction of less than 45% had a reduced ejection fraction (PH-HFrEF).

Figure 2.. Survival Probability and Freedom From Cardiac Hospitalizations in Participants Undergoing a Right Heart Catheterization

A, Precapillary pulmonary hypertension (PH) and PH in the setting of left heart disease (PH-LHD) both increase the risk of mortality in participants that have undergone a right heart catheterization. B, Participants with PH-LHD have more acute cardiac hospitalizations than participants without PH and precapillary PH. C, Participants in the PH-LHD group that have a reduced ejection fraction (PH-HFrEF) have increased mortality compared with those with preserved ejection fraction (PH-HFpEF) and precapillary PH. D, Both PH-HFrEF and PH-HFpEF groups have more acute cardiac associated hospitalizations than precapillary PH. Shaded areas indicate 95% CI.

Figure 3.. Elevated TPG, PVR, and DPG Are Associated With Increased Mortality in the PH-HFpEF Cohort

Transpulmonary gradient (TPG) (A), pulmonary vascular resistance (PVR) (B), and diastolic pulmonary gradient (DPG) (C) are associated with increased mortality. WU indicates Wood units.