Pulmonary Capillary Wedge Pressure Patterns During Exercise Predict Exercise Capacity and Incident Heart Failure

Abstract

Background: Single measurements of left ventricular filling pressure at rest lack sensitivity for identifying heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea on exertion. We hypothesized that exercise hemodynamic measurements (ie, changes in pulmonary capillary wedge pressure [PCWP] indexed to cardiac output [CO]) may more sensitively differentiate HFpEF and non-HFpEF disease states, reflect aerobic capacity, and forecast heart failure outcomes in individuals with normal PCWP at rest.

Methods and results: We studied 175 patients referred for cardiopulmonary exercise testing with hemodynamic monitoring: controls (n=33), HFpEF with resting PCWP≥15 mm Hg (n=32), and patients with dyspnea on exertion with normal resting PCWP and left ventricular ejection fraction (DOE-nlrW; n=110). Across 1835 paired PCWP-CO measurements throughout exercise, we used regression techniques to define normative bounds of "PCWP/CO slope" in controls and tested the association of PCWP/CO slope with exercise capacity and composite cardiac outcomes (defined as cardiac death, incident resting PCWP elevation, or heart failure hospitalization) in the DOE-nlrW group. Relative to controls (PCWP/CO slope, 1.2±0.4 mm Hg/L/min), patients with HFpEF had a PCWP/CO slope of 3.4±1.9 mm Hg/L/min. We used a threshold (2 SD above the mean in controls) of 2 mm Hg/L/min to define abnormal. PCWP/CO slope >2 in DOE-nlrW patients was common (n=45/110) and was associated with reduced peak Vo₂ (P<0.001) and adverse cardiac outcomes after adjustment for age, sex, and body mass index (hazard ratio, 3.47; P=0.03) at a median 5.3-year follow-up.

Conclusions: Elevated PCWP/CO slope during exercise (>2 mm Hg/L/min) is common in DOE-nlrW and predicts exercise capacity and heart failure outcomes. These findings suggest that current definitions of HFpEF based on single measures during rest are insufficient and that assessment of exercise PCWP/CO slope may refine early HFpEF diagnosis.

Keywords: cardiac output; dyspnea; exercise physiology; heart failure; pulmonary capillary wedge pressure.

Figure 1

Pulmonary capillary wedge pressure versus cardiac output measurements across two cohorts: HFpEF and healthy controls. The data has been pooled using the method of Poon to correct for differing numbers of data points (minutes of exercise) for each patient when calculating mean slope and standard deviation. The hashed line represents a PCWP/CO slope of 2.0, which nearly perfectly discriminates the two groups.

Figure 2

Box plots showing the difference between patients with PCWP/CO slope ≤ 2 vs. >2mmHg/L/min in peak VO2 (Panel A) and VE/VCO2 slope (Panel B). Tests of difference were performed using a Wilcoxon rank-sum test.

Figure 3

Event-free survival in the absence of the composite endpoint of HF hospitalization, death, or elevated pulmonary capillary wedge pressure (defined in text). Individuals with a lower PCWP/CO slope have an improved event-free survival (log-rank P=0.004).