Author + information
- Received August 6, 2019
- Revision received October 8, 2019
- Accepted October 22, 2019
- Published online January 6, 2020.
- Jennifer E. Ho, MDa,b,∗ (, )@JenHoCardiology,
- Emily K. Zern, MDb,
- Emily S. Lau, MDb,
- Luke Wooster, BSb,
- Cole S. Bailey, BAb,
- Thomas Cunningham, BSb,
- Aaron S. Eisman, BSb,
- Kathryn M. Hardin, BSb,
- Robyn Farrell, BSb,
- John A. Sbarbaro, BAb,
- Mark W. Schoenike, BSb,
- Nicholas E. Houstis, MD, PhDb,
- Aaron L. Baggish, MDb,
- Ravi V. Shah, MDb,
- Matthew Nayor, MD, MPHb,
- Rajeev Malhotra, MDa,b and
- Gregory D. Lewis, MDb,c,∗∗ (, )@GLewisCardiol
- aCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts
- bCardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
- cDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
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.
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.
- Received August 6, 2019.
- Revision received October 8, 2019.
- Accepted October 22, 2019.
- 2020 American College of Cardiology Foundation
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