Pulmonary vascular response patterns during exercise in left ventricular systolic dysfunction predict exercise capacity and outcomes

Abstract

Background: Elevated resting pulmonary arterial pressure (PAP) in patients with left ventricular systolic dysfunction (LVSD) purports a poor prognosis. However, PAP response patterns to exercise in LVSD and their relationship to functional capacity and outcomes have not been characterized.

Methods and results: Sixty consecutive patients with LVSD (age 60±12 years, left ventricular ejection fraction 0.31±0.07, mean±SD) and 19 controls underwent maximum incremental cardiopulmonary exercise testing with simultaneous hemodynamic monitoring. During low-level exercise (30 W), LVSD subjects, compared with controls, had greater augmentation in mean PAPs (15±1 versus 5±1 mm Hg), transpulmonary gradients (5±1 versus 1±1 mm Hg), and effective pulmonary artery elastance (0.05±0.02 versus -0.03±0.01 mm Hg/mL, P<0.0001 for all). A linear increment in PAP relative to work (0.28±0.12 mm Hg/W) was observed in 65% of LVSD patients, which exceeded that observed in controls (0.07±0.02 mm Hg/W, P<0.0001). Exercise capacity and survival was worse in patients with a PAP/watt slope above the median than in patients with a lower slope. In the remaining 35% of LVSD patients, exercise induced a steep initial increment in PAP (0.41±0.16 mm Hg/W) followed by a plateau. The plateau pattern, compared with a linear pattern, was associated with reduced peak Vo(2) (10.6±2.6 versus 13.1±4.0 mL · kg(-1) · min(-1), P=0.005), lower right ventricular stroke work index augmentation with exercise (5.7±3.8 versus 9.7±5.0 g/m(2), P=0.002), and increased mortality (hazard ratio 8.1, 95% CI 2.7 to 23.8, P<0.001).

Conclusions: A steep increment in PAP during exercise and failure to augment PAP throughout exercise are associated with decreased exercise capacity and survival in patients with LVSD, and may therefore represent therapeutic targets.

Clinical trial information: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00309790.

Figure 1

Representative patterns of pulmonary arterial pressure (PAP) and pulmonary capillary wedge pressure (PCWP) responses to exercise in normal controls (top), patients with LVSD with a linear PAP increment with exercise (middle), and patients with LVSD with a PAP plateau pattern during exercise (bottom).

Figure 2

(Panel A): Mean changes in pulmonary arterial pressure (Δ PAP) at 30 Watts and at peak exercise, compared to resting values, in patients with LVSD and controls. The relative contributions of pulmonary capillary wedge pressure (Δ PCWP) and transpulmonary gradient (Δ TPG) to Δ PAP are displayed on the right side of the panel. (Panel B): Mean changes in systemic arterial blood pressure (Δ MAP) in response to exercise in patients with LVSD and controls. * Indicates P<0.005 for the comparison of pressure changes in patients with LVSD with pressure changes in controls.

Figure 3

(Left panel) Mean pulmonary arterial pressures (PAP) relative to cardiac outputs during incremental exercise in patients with LVSD. (Right panels) Transpulmonary gradient (TPG) and pulmonary capillary wedge pressure (PCWP) responses to exercise relative to cardiac output augmentation in patients with LVSD. * Indicates P<0.005 for the comparison of pressure changes in patients with LVSD with pressure changes in controls

Figure 4

Kaplan-Meier survival estimates for LVSD patients with linear pulmonary arterial pressure (PAP) responses to exercise stratified by median PAP slope (<0.25 mmHg/W, top line, and ≥ 0.25 mmHg/W, middle line), as well as by plateau pattern (bottom line).

Figure 5

Effect of sildenafil on pulmonary vascular responses to exercise. Exercise-induced increases in pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), and transpulmonary gradient (TPG) at 30 Watts. Sildenafil blunted the TPG augmentation with exercise. *P=0.02.