Clinical features, hemodynamics, and outcomes of pulmonary hypertension due to chronic heart failure with reduced ejection fraction: pulmonary hypertension and heart failure

Objectives: The purpose of this study was to assess the clinical, functional, and hemodynamic characteristics of passive and mixed pulmonary hypertension (PH), compare outcomes, and contrast conventional and novel hemodynamic partition values in patients with chronic heart failure of reduced left ventricular ejection fraction (HFREF).

Background: PH in HFREF may develop from left-sided venous congestion (passive PH) or the combination of pulmonary arterial disease and venous congestion (mixed PH). Subgroup outcomes are not well defined, and the partition values used to define risk are based largely on consensus opinion rather than outcome data.

Methods: Ambulatory patients referred for hemodynamic catheterization were analyzed retrospectively (N = 463).

Results: Comparing patients with no PH to those with passive PH and mixed PH, a progressive gradient of more severely deranged hemodynamics, diastolic dysfunction, and mitral regurgitation was observed. In multivariate analysis, the presence of any PH or mixed PH was associated with older age, diuretic use, atrial fibrillation, and lower pulmonary artery compliance (PAC). Over a median follow-up of 2.1 years, patients with PH displayed greater risk of death (hazard ratio [HR]: 2.24; confidence limits [95% CL]: 1.39, 3.98; p < 0.001) with mixed PH demonstrating greater risk than passive PH (HR: 1.55; 95% CL: 1.11, 2.20; p < 0.001). Partition values identifying highest risk were pulmonary vascular resistance >4 Wood units, systolic pulmonary artery pressure >35 mm Hg, pulmonary wedge pressure >25 mm Hg, and PAC <2.0 ml/mm Hg.

Conclusions: Among stable HFREF outpatients, PH was associated with markers of greater disease severity and risk of death. However, the presence of pulmonary arterial disease (mixed PH) carries incremental risk. Abnormalities in pulmonary vascular resistance and compliance may serve as novel therapeutic targets.