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

https://doi.org/10.1016/j.jacc.2019.10.048Get rights and content
Under an Elsevier user license
open archive

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.

Key Words

cardiovascular disease
exercise
pulmonary hypertension

Abbreviations and Acronyms

CI
confidence interval
CO
cardiac output
COPD
chronic obstructive pulmonary disease
CPET
cardiopulmonary exercise testing
CV
cardiovascular
DLCO
diffusion capacity of carbon monoxide
exPH
exercise pulmonary hypertension
FEV1
forced expiratory volume in 1 second
FVC
forced vital capacity
HR
hazard ratio
ILD
interstitial lung disease
PAP
mean pulmonary artery pressure
PCWP
pulmonary capillary wedge pressure
PH
pulmonary hypertension
TPG
transpulmonary gradient

Cited by (0)

This work was supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute R01-HL134893 (JEH), R01-HL140224 (JEH), R01-HL142809 (RM), and R01-HL131029 (GDL); a Gilead Sciences Research Scholar Award (JEH); and the American Heart Association 15GPSGC24800006 (GDL) and the MGH Heart Failure Research Innovation Fund. Sponsors had no role in the design, conduct, or decision to publish the work. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.