Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study

Abstract

Objectives: This study sought to define the prevalence, severity, and significance of pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) in the general community.

Background: Although HFpEF is known to cause PH, its development is highly variable. Community-based data are lacking, and the relative contribution of pulmonary venous versus pulmonary arterial hypertension (HTN) to PH in HFpEF is unknown. We hypothesized that PH would be a marker of symptomatic pulmonary congestion, distinguishing HFpEF from pre-clinical hypertensive heart disease.

Methods: This community-based study of 244 HFpEF patients (age 76 +/- 13 years; 45% male) was followed up using Doppler echocardiography over 3 years. Control subjects were 719 adults with HTN without HF (age 66 +/- 10 years; 44% male). Pulmonary artery systolic pressure (PASP) was derived from the tricuspid regurgitation velocity and PH defined as PASP >35 mm Hg. Pulmonary capillary wedge pressure (PCWP) was estimated from the ratio of early transmitral flow velocity to early mitral annular diastolic velocity.

Results: In HFpEF, PH was present in 83% and the median (25th, 75th percentile) PASP was 48 (37, 56) mm Hg. PASP increased with PCWP (r = 0.21; p < 0.007). Adjusting for PCWP, PASP was higher in HFpEF than HTN (p < 0.001). The PASP distinguished HFpEF from HTN with an area under the receiver-operating characteristic curve of 0.91 (p < 0.001) and strongly predicted mortality in HFpEF (hazard ratio: 1.3 per 10 mm Hg; p < 0.001).

Conclusions: PH is highly prevalent and often severe in HFpEF. Although pulmonary venous HTN contributes to PH, it does not fully account for the severity of PH in HFpEF, suggesting that a component of pulmonary arterial HTN also contributes. The potent effect of PASP on mortality lends support for therapies aimed at pulmonary arterial HTN in HFpEF.

Figure 1. Cumulative frequency distribution of pulmonary artery systolic pressure and prevalence of pulmonary hypertension by subject group

In patients with heart failure and preserved ejection fraction (HFpEF, in red), the cumulative frequency distribution of pulmonary artery systolic pressure (PASP) was shifted towards higher pressures (A), while the prevalence of pulmonary hypertension (PH) was markedly increased (B), compared to subjects with hypertension (HTN, in black) without heart failure in the community.

Figure 2. Association of pulmonary artery systolic pressure with pulmonary venous hypertension

Pulmonary artery systolic pressure (PASP) increased with pulmonary capillary wedge pressure (PCWP) in patients with heart failure and preserved ejection fraction (HFpEF), as well as in subjects with hypertension (HTN) without heart failure, but remained higher in HFpEF than HTN after adjusting for PCWP (p<0.001). Raw data points and linear regression line for the association are shown for HFpEF (in red) and HTN (in black).

Figure 3. Receiver operating curves of echocardiographic parameters for the diagnosis of heart failure with preserved ejection fraction

By receiver operating curve analysis, echocardiographic parameters that distinguished heart failure with preserved ejection fraction (HFpEF) from hypertensive (HTN) heart disease without heart failure included pulmonary artery systolic pressure (PASP), E/e’ ratio, left atrial volume index and relative wall thickness. The largest area under curve was obtained with PASP, with the optimal cutoff value of 35 mmHg.

Figure 4. Kaplan-Meier survival curves in HFpEF patients with pulmonary artery systolic pressure above and below the median

HFpEF patients with pulmonary artery systolic pressure (PASP) above the median value of 48 mmHg (in red) had reduced survival compared to patients with PASP<48 mmHg (in black) over 3 years (Log rank p=0.002).