Pulmonary Arterial Capacitance Is an Important Predictor of Mortality in Heart Failure With a Preserved Ejection Fraction

Abstract

Objectives: The purpose of this study was to determine the predictors of mortality in patients with pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (HFpEF).

Background: PH is commonly associated with HFpEF. The predictors of mortality for patients with these conditions are not well characterized.

Methods: In a prospective cohort of patients with right heart catheterization, we identified 73 adult patients who had pulmonary hypertension due to left heart disease (PH-LHD) associated with HFpEF (left ventricular ejection fraction ≥50% by echocardiography); hemodynamically defined as a mean pulmonary artery pressure ≥25 mm Hg and pulmonary artery wedge pressure >15 mm Hg. PH severity was classified according to the diastolic pressure gradient (DPG). Cox proportional hazards ratios were used to estimate the associations between clinical variables and mortality. Receiver-operating characteristic curves were used to evaluate the ability of hemodynamic measurements to predict mortality.

Results: The mean age for study subjects was 69 ± 12 years and 74% were female. Patients classified as having combined post-capillary PH and pre-capillary PH (DPG ≥7) were not at increased risk of death as compared to patients with isolated post-capillary PH (DPG <7). A baseline pulmonary arterial capacitance (PAC) of <1.1 ml/mm Hg was 91% sensitive in predicting mortality, with better discriminatory ability than DPG, transpulmonary gradient, or pulmonary vascular resistance (area under the curve of 0.73, 0.50, 0.45, and 0.37, respectively). Fifty-seven subjects underwent acute vasoreactivity testing with inhaled nitric oxide. Acute vasodilator response by the Rich or Sitbon criteria was not associated with improved survival.

Conclusions: PAC is the best predictor of mortality in our cohort and may be useful in describing phenotypic subgroups among those with PH-LHD associated with HFpEF. Acute vasodilator testing did not predict outcome in our cohort but needs to be further investigated.

Keywords: heart failure with preserved ejection fraction; pulmonary heart disease; survival; vasodilation.

FIGURE 1. Flow Chart for Patients Included in Study

This figure illustrates the selection process of our study cohort. *Patients with moderate-severe aortic or mitral valve disease were excluded. Comb-PH = combined post-capillary pulmonary hypertension and pre-capillary pulmonary hypertension; HFpEF = heart failure with preserved ejection fraction; Iso-PH = isolated post-capillary pulmonary hypertension; LVEF = left ventricular ejection fraction; mPAP = mean pulmonary artery pressure; PAWP = pulmonary artery wedge pressure; PH-LHD = pulmonary hypertension due to left heart disease; RHC = right heart catheterization.

FIGURE 2. Receiver-Operating Characteristic Curves for Prediction of Mortality

Receiver-operating characteristic curves for each of the hemodynamic parameters (pulmonary arterial capacitance [PAC], diastolic pressure gradient [DPG], transpulmonary gradient [TPG], and pulmonary vascular resistance [PVR]) and prediction of mortality during the study follow-up period (n = 73). AUC = area under the curve; CI = confidence interval.

FIGURE 3. Survival of Patients With PH-LHD and HFpEF

Kaplan-Meier estimates of survival in patients with pulmonary hypertension due to left heart disease (PH-LHD) and heart failure with preserved ejection fraction (HFpEF) relative to pulmonary hypertension severity as defined by pulmonary arterial capacitance (PAC) <1.1 ml/mm Hg or ≥1.1 ml/mm Hg (n = 73).