Exercise Pulmonary Hypertension Predicts Clinical Outcomes in Patients With Dyspnea on Effort

Abstract

Background: Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described in select individuals; however, clinical and prognostic implications of exercise pulmonary hypertension (exPH) among broader samples remains unclear.

Objectives: This study sought to investigate the association of exPH with clinical determinants and outcomes.

Methods: The authors studied individuals with chronic exertional dyspnea and preserved ejection fraction who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring. Exercise pulmonary hypertension was ascertained using minute-by-minute PAP and cardiac output (CO) measurements to calculate a PAP/CO slope, and exPH defined as a PAP/CO slope >3 mm Hg/l/min. The primary outcome was cardiovascular (CV) hospitalization or all-cause mortality.

Results: Among 714 individuals (age 57 years, 59% women), 296 (41%) had abnormal PAP/CO slopes. Over a mean follow-up of 3.7 ± 2.9 years, there were 208 CV or death events. Individuals with abnormal PAP/CO slope had a 2-fold increased hazard of future CV or death event (multivariable-adjusted hazard ratio: 2.03; 95% confidence interval: 1.48 to 2.78; p < 0.001). The association of abnormal PAP/CO slope with outcomes remained significant after excluding rest PH (n = 146, hazard ratio: 1.75; 95% confidence interval: 1.21 to 2.54; p = 0.003). Both pre- and post-capillary contributions to exPH independently predicted adverse events (p < 0.001 for both).

Conclusions: Exercise pulmonary hypertension is independently associated with CV event-free survival among individuals undergoing evaluation of chronic dyspnea. These findings suggest incremental value of exercise hemodynamic assessment to resting measurements alone in characterizing the burden of PH in individuals with dyspnea. Whether PH and PH subtypes unmasked by exercise can be used to guide targeted therapeutic interventions requires further investigation.

Keywords: cardiovascular disease; exercise; pulmonary hypertension.

Figure 1.. Pulmonary hemodynamic responses to exercise are associated with future clinical outcomes.

Kaplan-Meier curves for clinical outcomes in patients with high PAP/CO slope (defined as PAP/CO slope >3 mmHg/L/min, shown in solid line) vs normal PAP/CO slope (dotted line). Panel A shows combined primary endpoint of CV hospitalization or all-cause death, panel B shows CV hospitalization, and panel C shows all-cause death.

Central Illustration. Cardiovascular Event-Free Survival Among Individuals with Dyspnea by Pulmonary Hypertension Status.

Colors designate those without PH (blue), rest PH (red, defined as rest PAP >20 mmHg), and exercise PH (yellow, defined as rest PAP ≤20 mmHg and PAP/CO slope >3 mmHg/L/min).